Search results for: therapeutic exercises

Authors: Nigatu Tadesse, Li Juan, Liuhong Ming

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Gastric cancer (GC) is the fifth most common and fourth deadly cancer in the world with limited treatment options at late advanced stage in which surgical therapy is not recommended with chemotherapy remain as the mainstay of treatment. However, the occurrence of chemoresistance as well as intera-tumoral and inter-tumoral heterogeneity of response to targeted and immunotherapy underlined a clear unmet treatment need in gastroenterology. Several molecular and cellular alterations ascribed for chemo resistance in GC including cancer stem cells (CSC) and tumor microenvironment (TME) remodeling. Cancer cells including CSC bears higher metabolic demand and major changes in TME involves alterations of gut microbiota interacting with nutrients metabolism. Metabolic upregulation in lipids, carbohydrates, amino acids, fatty acids biosynthesis pathways identified as a common hall mark in GC. Metabolic addiction to methionine metabolism occurs in many cancer cells to promote the biosynthesis of S-Adenosylmethionine (SAM), a universal methyl donor molecule for high rate of transmethylation in GC and promote cell proliferation. Targeting methionine metabolism found to promotes chemo-sensitivity with treatment non-heterogeneity. Methionine restriction (MR) promoted the arrest of cell cycle at S/G2 phase and enhanced downregulation of GC cells resistance to apoptosis (including ferroptosis), which suggests the potential of synergy with chemotherapies acting at S-phase of the cell cycle as well as inducing cell apoptosis. Accumulated evidences showed both the biogenesis as well as intracellular metabolism of exogenous methionine could be safe and effective target for therapy either alone or in combination with chemotherapies. This review article provides an over view of the upregulation in methionine biosynthesis pathway and the molecular signaling through the PI3K/Akt/mTOR-c-MYC axis to promote metabolic reprograming through activating the expression of L-type aminoacid-1 (LAT1) transporter and overexpression of Methionine adenosyltransferase 2A(MAT2A) for intercellular metabolic conversion of exogenous methionine to SAM in GC, and the potential of targeting with novel therapeutic agents such as methioninase (METase), Methionine adenosyltransferase 2A (MAT2A), c-MYC, methyl like transferase 16 (METTL16) inhibitors that are currently under clinical trial development stages and future perspectives.

Keywords: gastric cancer, methionine metabolism, pi3k/akt/mtorc1-c-myc axis, gut microbiota, MAT2A, c-MYC, METTL16, methioninase

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Authors: Moizza Tahir, Uzma Bashir, Aisha Akhtar, Zainab Ansari, Sameen Ansari, Muhammad Ali Tahir

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Cancer burden has globally increased. Among cutaneous cancers basal cell carcinoma constitute vast majority of skin cancer. There is need for appropriate diagnostic, therapeutic and prognostic significance evaluation for skin cancers Present study report intraoperative frozen section (FS) histopathological clearance for excision of BCC in a tertiary care center and find the frequency of involvement of surgical margin with reference to anatomical site, with size and surgical technique. It was prospective open label interventional study conducted at Dermatology department of tertiary care hospital Rawalpindi Pakistan in lais on with histopathology department from January 2023 to April 2024. Total of thirty-six (n = 36) patients between age 45-80 years with basal cell carcinoma of 10-20mm on face were included following inclusion exclusion criteria by purposive sampling technique. Informed consent was taken. Surgical excision was performed and intraoperative frozen section histopathology clearance of tumor margin was taken from histopathologist on telephone. Surgical reconstruction was done. Final Histopathology report was reexamined on day 10th for margin and depth clearance. Descriptive statistics were calculated for age, gender, sun exposure, reconstructive technique, anatomical site, and tumor free margin report on frozen section analysis. Chi square test was employed for statistical significance of involvement of surgical margin with reference to anatomical site, size and decision on reconstructive surgical technique, p value of <0.05 was considered significant. Total of 36 patients of BCC were enrolled, males 12 (33.3%) and females were 24 (66.6%). Age ranged from 45 year to 80 year mean of 58.36 ±SD7.8. Size of BCC ranged from 10mm to 35mm mean of 25mm ±SD 0.63. Morphology was nodular 18 (50%), superficial spreading 11(30.6%), morphoeic 1 (2.8%) and ulcerative in 6(16.7%) cases. Intraoperative frozen section for histopathological margin clearance with 2-3 mm safety margin and surgical technique has p-value0.51, for anatomical site p value 0.24 and size p-0.84. Intraoperative frozen section (FS) histopathological clearance for BCC face with 2-3mm safety margin with reference to reconstructive technique, anatomical site and size of BCC were insignificant.

Keywords: basal cell carcinoma, tumor free amrgin, basal cell carcinoma and frozen section, safety margin

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Authors: Taiwo O. Margaret, Olaoluwa O. Olaoluwa

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Moraceae family has immense phytochemical constituents and significant pharmacological properties, hence have great medicinal values. The aim of this study was to screen and quantify phytochemicals as well as the antioxidant activities of the leaf and stem bark extracts and fractions (crude ethanol extracts, n-hexane, ethyl acetate and aqueous ethanol fractions) of Ficus sagittifolia. Leaf and stem bark of F. sagittifolia were extracted by maceration method using ethanol to give ethanol crude extract. The ethanol crude extract was partitioned by n-hexane and ethyl-acetate to give their respective fractions. All the extracts were screened for their phytochemicals using standard methods. The total phenolic, flavonoid, tannin, saponin contents and antioxidant activity were determined by spectrophotometric method while the alkaloid content was evaluated by titrimetric method. The amount of total phenolic in extracts and fractions were estimated in comparison to gallic acid, whereas total flavonoids, tannins and saponins were estimated corresponding to quercetin, tannic acid and saponin respectively. 2, 2-diphenylpicryl hydrazyl radical (DPPH)* and phosphomolybdate methods were used to evaluate the antioxidant activities of leaf and stem bark of F. sagittifolia. Phytochemical screening revealed the presence of flavonoids, saponins, terpenoids/steroids, alkaloids for both extracts of leaf and stem bark of F. sagittifolia. The phenolic content of F. sagittifolia was most abundant in leaf ethanol crude extract as 3.53 ± 0.03 mg/g equivalent of gallic acid. Total flavonoids and tannins content were highest in stem bark aqueous ethanol fraction of F. sagittifolia estimated as 3.41 ± 0.08 mg/g equivalent of quercetin and 1.52 ± 0.05 mg/g equivalent of tannic acid respectively. The hexane leaf fraction of F. sagittifolia had the utmost saponin and alkaloid content as 5.10 ± 0.48 mg/g equivalent of saponins and 0.171 ± 0.39 g of alkaloids. Leaf aqueous ethanol fraction of F. sagittifolia showed high antioxidant activity (IC₅₀ value of 63.092 µg/mL) and stem ethanol crude extract (227.43 ± 0.78 mg/g equivalent of ascorbic acid) for DPPH and phosphomolybdate method respectively and the least active was found to be the stem hexane fraction using both methods (313.32 µg/mL; 16.21 ± 1.30 mg/g equivalent of ascorbic acid). The presence of these phytochemicals in the leaf and stem bark of F. sagittifolia are responsible for their therapeutic importance as well as the ability to scavenge free radicals in living systems.

Keywords: Moraceae, Ficus sagittifolia, phytochemicals, antioxidant

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Authors: Jae-Hyeon Kim, Michael Lee

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Intrinsic and acquired resistance limits the therapeutic benefits of oncogenic BRAF inhibitors in melanoma. MicroRNAs (miRNA) regulate the expression of target mRNAs by repressing their translation. Thus, we investigated miRNA expression patterns in melanoma cell lines to identify candidate biomarkers for acquired resistance to BRAF inhibitor. Here, we used Affymetrix miRNA V3.0 microarray profiling platform to compare miRNA expression levels in three cell lines containing BRAF inhibitor-sensitive A375P BRAF V600E cells, their BRAF inhibitor-resistant counterparts (A375P/Mdr), and SK-MEL-2 BRAF-WT cells with intrinsic resistance to BRAF inhibitor. The miRNAs with at least a two-fold change in expression between BRAF inhibitor-sensitive and –resistant cell lines, were identified as differentially expressed. Averaged intensity measurements identified 138 and 217 miRNAs that were differentially expressed by 2 fold or more between: 1) A375P and A375P/Mdr; 2) A375P and SK-MEL-2, respectively. The hierarchical clustering revealed differences in miRNA expression profiles between BRAF inhibitor-sensitive and –resistant cell lines for miRNAs involved in intrinsic and acquired resistance to BRAF inhibitor. In particular, 43 miRNAs were identified whose expression was consistently altered in two BRAF inhibitor-resistant cell lines, regardless of intrinsic and acquired resistance. Twenty five miRNAs were consistently upregulated and 18 downregulated more than 2-fold. Although some discrepancies were detected when miRNA microarray data were compared with qPCR-measured expression levels, qRT-PCR for five miRNAs (miR-3617, miR-92a1, miR-1246, miR-1936-3p, and miR-17-3p) results showed excellent agreement with microarray experiments. To further investigate cellular functions of miRNAs, we examined effects on cell proliferation. Synthetic oligonucleotide miRNA mimics were transfected into three cell lines, and proliferation was quantified using a colorimetric assay. Of the 5 miRNAs tested, only miR-1246 altered cell proliferation of A375P/Mdr cells. The transfection of miR-1246 mimic strongly conferred PLX-4720 resistance to A375P/Mdr cells, implying that miR-1246 upregulation confers acquired resistance to BRAF inhibition. We also found that PLX-4720 caused much greater G2/M arrest in A375P/Mdr cells transfected with miR-1246mimic than that seen in scrambled RNA-transfected cells. Additionally, miR-1246 mimic partially caused a resistance to autophagy induction by PLX-4720. These results indicate that autophagy does play an essential death-promoting role inPLX-4720-induced cell death. Taken together, these results suggest that miRNA expression profiling in melanoma cells can provide valuable information for a network of BRAF inhibitor resistance-associated miRNAs.

Keywords: microRNA, BRAF inhibitor, drug resistance, autophagy

Procedia PDF Downloads 296

Authors: Amin Masoumiganjgah, Luke Salmon, Julianne Burnton, Fahimeh Bagheri, Gavin Lenton, S. L. Ezekial Tan

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Introduction: The incidence of proximal biceps tenodesis and acute distal biceps repair is increasing, and rehabilitation protocols following both are variable. Golf is a popular sport within Australia, and the Gold Coast has become a Mecca for golfers, with more courses per capita than anywhere else in the world. Currently, there are no clear guidelines regarding return to golf play following biceps procedures. The aim of this study was to determine biceps brachii activation during the golf swing through electromyographic analysis, and subsequently, aid in rehabilitation guidelines and return to golf following tenodesis and repair. Methods: Subjects were amateur golfers with no previous upper limb surgery. Surface electromyography (EMG) and high-speed video recording were used to analyse activation of the left and right biceps brachii and the anterior deltoid during the golf swing. Each participant’s maximum voluntary contraction (MVC) was recorded, and they were then required to hit a golf ball aiming for specific distances of 2, 50, 100 and 150 metres at a driving range. Noraxon myoResearch and Matlab were used for data analysis. Mean % MVC was calculated for leading and trailing arms during the full swing and its’ 4 phases: back-swing, acceleration, early follow-through and late follow-through. Results: 12 golfers (2 female and 10 male), participated in the study. Median age was 27 (25 – 38), with all being right handed. Over all distances, the mean activation of the short and long head of biceps brachii was < 10% through the full swing. When breaking down the 50, 100 and 150m swing into phases, mean MVC activation was lowest in backswing (5.1%), followed by acceleration (9.7%), early follow-through (9.2%), and late follow-through (21.4%). There was more variation and slightly higher activation in the right biceps (trailing arm) in backswing, acceleration, and early follow-through; with higher activation in the leading arm in late follow-through (25.4% leading, 17.3% trailing). 2m putts resulted in low MVC values (3.1% ) with little variation across swing phases. There was considerable individual variation in results – one tense subject averaged 11.0% biceps MVC through the 2m putting stroke and others recorded peak mean MVC biceps activations of 68.9% at 50m, 101.3% at 100m, and 111.3% at 150m. Discussion: Previous studies have investigated the role of rotator cuff, spine, and hip muscles during the golf swing however, to our knowledge, this is the first study that investigates the activation of biceps brachii. Many rehabilitation programs following a biceps tenodesis or repair allow active range against gravity and restrict strengthening exercises until 6 weeks, and this does not appear to be associated with any adverse outcome. Previous studies demonstrate a range of < 10% MVC is similar to the unloaded biceps brachii during walking(1), active elbow flexion with the hand positioned either in pronation or supination will produce MVC < 20% throughout range(2) and elbow flexion with a 4kg dumbbell can produce mean MVC’s of around 40%(3). Our study demonstrates that increasing activation is associated with the leading arm, increasing shot distance and the late follow-through phase. Although the cohort mean MVC of the biceps brachii is <10% through the full swing, variability is high and biceps activation reach peak mean MVC’s of over 100% in different swing phases for some individuals. Given these EMG values, caution is advised when advising patients post biceps procedures to return to long distance golf shots, particularly when the leading arm is involved. Even though it would appear that putting would be as safe as having an unloaded hand out of a sling following biceps procedures, the variability of activation patterns across different golfers would lead us to caution against accelerated golf rehabilitation in those who may be particularly tense golfers. The 50m short iron shot was too long to consider as a chip shot and more work can be done in this area to determine the safety of chipping.

Keywords: electromyographic analysis, biceps brachii rupture, golf swing, tendon surgery

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Authors: Bruno R. Mendes, Francisco J. Caldeira, Rita S. Luís

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Population ageing is directly correlated to an increase in medicine consumption. Beyond the latter and the polymedicated profile of elderly, it is possible to see a need for pharmacotherapeutic monitoring due to cognitive and physical impairment. In this sense, the tracking, organization and administration of medicines become a daily challenge and the pill-box dispenser system a solution. The pill-box dispenser (system) consists in a small compartmentalized container to unit dose organization, which means a container able to correlate the patient’s prescribed dose regimen and the time schedule of intake. In many European countries, this system is part of pharmacist’s role in clinical pharmacy. Despite this simple solution, therapy compliance is only possible if the patient adheres to the system, so it is important to establish a qualitative and quantitative analysis on the perception of the patient on the benefits and risks of the pill-box dispenser as well as the identification of the ideal system. The analysis was conducted through an observational study, based on the application of a standardized questionnaire structured with the numerical scale of Likert (5 levels) and previously validated on the population. The study was performed during a limited period of time and under a randomized sample of 188 participants. The questionnaire consisted of 22 questions: 6 background measures and 16 specific measures. The standards for the final comparative analysis were obtained through the state-of-the-art on the subject. The study carried out using the Likert scale afforded a degree of agreement and discordance between measures (Sample vs. Standard) of 56,25% and 43,75%, respectively. It was concluded that the pill-box dispenser has greater acceptance among a younger population, that was not the initial target of the system. However, this allows us to guarantee a high adherence in the future. Additionally, it was noted that the cost associated with this service is not a limiting factor for its use. The pill-box dispenser system, as currently implemented, demonstrates an important weakness regarding the quality and effectiveness of the medicines, which is not understood by the patient, revealing a significant lack of literacy when it concerns with medicine area. The characteristics of an ideal system remain unchanged, which means that the size, appearance and availability of information in the pill-box continue to be indispensable elements for the compliance with the system. The pill-box dispenser remains unsuitable regarding container size and the type of treatment to which it applies. Despite that, it might be a future standard for clinical pharmacy, allowing a differentiation of the pharmacist role, as well as a wider range of applications to other age groups and treatments.

Keywords: clinical pharmacy, medicines, patient safety, pill-box dispenser

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Authors: Tais Basaco, Stefanie Pektor, Josue A. Moreno, Matthias Miederer, Andreas Türler

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Radiopharmaceuticals based in monoclonal anti-body (mAb) via chemical linkers have become a potential tool in nuclear medicine because of their specificity and the large variability and availability of therapeutic radiometals. It is important to identify the conjugation sites and number of attached chelator to mAb to obtain radioimmunoconjugates with required immunoreactivity and radiostability. Girentuximab antibody (G250) is a potential candidate for radioimmunotherapy of clear cell carcinomas (RCCs) because it is reactive with CAIX antigen, a transmembrane glycoprotein overexpressed on the cell surface of most ( > 90%) (RCCs). G250 was conjugated with the bifunctional chelating agent DOTA (1,4,7,10-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid) via a benzyl-thiocyano group as a linker (p-SCN-Bn-DOTA). DOTA-G250 conjugates were analyzed by size exclusion chromatography (SE-HPLC) and by electrophoresis (SDS-PAGE). The potential site-specific conjugation was identified by liquid chromatography–mass spectrometry (LC/MS-MS) and the number of linkers per molecule of mAb was calculated using the molecular weight (MW) measured by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The average number obtained in the conjugates in non-reduced conditions was between 8-10 molecules of DOTA per molecule of mAb. The average number obtained in the conjugates in reduced conditions was between 1-2 and 3-4 molecules of DOTA per molecule of mAb in the light chain (LC) and heavy chain (HC) respectively. Potential DOTA modification sites of the chelator were identified in lysine residues. The biological activity of the conjugates was evaluated by flow cytometry (FACS) using CAIX negative (SKRC-18) and CAIX positive (SKRC-52). The DOTA-G250 conjugates were labelled with 177Lu with a radiochemical yield > 95% reaching specific activities of 12 MBq/µg. The stability in vitro of different types of radioconstructs was analyzed in human serum albumin (HSA). The radiostability of 177Lu-DOTA-G250 at high specific activity was increased by addition of sodium ascorbate after the labelling. The immunoreactivity was evaluated in vitro and in vivo. Binding to CAIX positive cells (SK-RC-52) at different specific activities was higher for conjugates with less DOTA content. Protein dose was optimized in mice with subcutaneously growing SK-RC-52 tumors using different amounts of 177Lu- DOTA-G250.

Keywords: mass spectrometry, monoclonal antibody, radiopharmaceuticals, radioimmunotheray, renal cancer

Procedia PDF Downloads 279

Authors: Emmanuel Ikechuckwu Onwubuya, Afees Adebayo Oladejo

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Background: The use of medicinal plants in the treatment of chronic diseases especially myocardial infarction, is gaining wide acceptance globally. Andrographis paniculata (Acanthaceae) is a medicinal plant commonly known as the king of bitters in Nigeria and has been acclaimed for several therapeutic activities. Materials and methods: This study investigated the cardio-protective effect of the leaf extract of A. paniculata in isoproterenol-induced myocardial infarction. Fresh green leaves of A paniculata were harvested from the Faculty of Agriculture farmland, Nnamdi Azikiwe University, Awka, Nigeria. Identification and authentication of the plant were carried out at the Department of Botany, Nnamdi Azikiwe University and a voucher specimen was deposited at the herbarium. The plant material was then shredded, air-dried under shade and pulverized. The fine powders obtained were weighed and extraction was done via a solvent combination of water and ethanol (3:7) for 72 hr via maceration. The filtrate gotten was evaporated to dryness to obtain the ethanol extract, which was used for further bioassay study. The bioactive constituents of the plant extract were quantitatively analyzed by Gas chromatography-mass spectrometry (GC-MS). The animals were administered the extract of A. paniculata orally for seven days at a divided dose of 100 mg/kg, 200 mg/kg and 400 mg/kg body weights. On the eighth day, myocardial infarction was induced through subcutaneous administration of isoproterenol at a dose of 150 mg/kg/day diluted in 2 ml of saline on two consecutive days. Subsequently, the blood pressures were monitored and blood was collected for bioassay studies. Results: The results of the study showed that the leaf extract of A. paniculata was rich in Dodecanoic acid (8.261%), 4-Dibenzofuranamine (6.03%), Cyclotrisiloxane (4.679 %). The findings also showed a significant decrease (p>0.05) in the Mean arterial blood pressure, heart rate, aspartate transaminase, alanine transaminase, creatinine kinase and lactate dehydrogenase activities of the treatment group compared with the untreated control group while the antioxidant (superoxide dismutase, catalase and glutathione) activities were significantly increased in the treatment group, compared with the untreated control group. Conclusion: The findings of this work have shown that the leaf of A. paniculata was rich in bioactive compounds, which could be synthesized to produce plant-based products to fight cardiovascular diseases, especially myocardial infarction.

Keywords: cardiovascular disease, myocardial infarction, medicinal plant, andrographis paniculata, isoproterenol

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Authors: Martina Šutovská, Marta Jošková, Ivana Kazimierová, Lenka Pappová, Maroš Adamkov, Soňa Fraňová

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Bronchial asthma is characterized by increased bronchoconstrictor responses to provoking agonists, airway inflammation and remodeling. All these processes involve Ca2+ influx through Ca2+-release-activated Ca2+ channels (CRAC) that are widely expressed in immune, respiratory epithelium and airway smooth muscle (ASM) cells. Our previous study pointed on possible therapeutic potency of CRAC blockers using experimental guinea pigs asthma model. Presented work analyzed complex anti-asthmatic effect of long-term administered CRAC blocker, including impact on allergic inflammation, airways hyperreactivity, and remodeling and mucociliary clearance. Ovalbumin-induced allergic inflammation of the airways according to Franova et al. was followed by 14 days lasted administration of CRAC blocker (3-fluoropyridine-4-carboxylic acid, FPCA) in the dose 1.5 mg/kg bw. For comparative purposes salbutamol, budesonide and saline were applied to control groups. The anti-inflammatory effect of FPCA was estimated by serum and bronchoalveolar lavage fluid (BALF) changes in IL-4, IL-5, IL-13 and TNF-α analyzed by Bio-Plex® assay as well as immunohistochemical staining focused on assessment of tryptase and c-Fos positivity in pulmonary samples. The in vivo airway hyperreactivity was evaluated by Pennock et al. and by organ tissue bath methods in vitro. The immunohistochemical changes in ASM actin and collagen III layer as well as mucin secretion evaluated anti-remodeling effect of FPCA. The measurement of ciliary beat frequency (CBF) in vitro using LabVIEW™ Software determined impact on mucociliary clearance. Long-term administration of FPCA to sensitized animals resulted in: i. Significant decrease in cytokine levels, tryptase and c-Fos positivity similar to budesonide effect; ii.Meaningful decrease in basal and bronchoconstrictors-induced in vivo and in vitro airway hyperreactivity comparable to salbutamol; iii. Significant inhibition of airway remodeling parameters; iv. Insignificant changes in CBF. All these findings confirmed complex anti-asthmatic effect of CRAC channels blocker and evidenced these structures as the rational target in the treatment of allergic bronchial asthma.

Keywords: allergic asthma, CRAC channels, cytokines, respiratory epithelium

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Authors: Rajish Shil, Mohammad Ali Houri, Mohammad Milad Ismail, Fatimah Al Kaabi

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The clinical presentation of Primary hyperparathyroidism can vary from simple asymptomatic hypercalcemia to severe life-threatening hypercalcemic crisis with multi-organ dysfunction, which can be due to parathyroid adenoma or sometimes with malignant cancer. This cascade of clinical presentation can lead to a diagnostic and therapeutic challenge for treating the disease. We are presenting a case of severe hypercalcemic crisis due to parathyroid adenoma with an emphasis on early management, diagnosis, and interventions to prevent any lifelong complications and any permanent organ dysfunction. A 30 years old female with a history of primary Infertility, admitted to Al Ain Hospital critical care unit with Acute Severe Necrotizing Pancreatitis. She initially had a 1-month history of abdominal pain on and off, for which she was treated conservatively with no much improvement, and later on, she developed life-threatening severe pancreatitis, which required her to be admitted to the critical care unit. She was transferred from a private healthcare facility, where she was found to have a very high level of calcium up to 15mmol/L. She received systemic Zoledronic Acid, which lowered her calcium level transiently and later was increased again. She went on to develop multiple end-organ damages along with multiple electrolytes disturbances. She was found to have high levels of Parathyroid hormone, which was correlated with a parathyroid mass on the neck via radiological imaging. After a long course of medical treatment to lower the calcium to a near-normal level, parathyroidectomy was done, which showed parathyroid adenoma on histology. She developed hungry bone syndrome after the surgery and pancreatic pseudocyst after resolving of pancreatitis. She required aggressive treatment with Intravenous calcium for her hypocalcemia as she received zoledronic acid at the beginning of the disease. Later on, she was discharged on long term calcium and other electrolytes supplements. In patients presenting with hypercalcemia, it is prudent to investigate and start treatment early to prevent complications and end-organ damage from hypercalcemia and also to treat the primary cause of the hypercalcemia, with conscious follow up to prevent hypocalcemic complications after treatment. It is important to follow up patients with parathyroid adenomas for a long period in order to detect any recurrence of the tumor or to make sure if the primary tumor is either benign or malignant.

Keywords: hypercalcemia, pancreatitis, hypocalcemia, hyperparathyroidism

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Authors: Inês N. Peça , A. Bicho, Rui Gardner, M. Margarida Cardoso

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Inorganic/organic nanocomplexes offer tremendous scope for future biomedical applications, including imaging, disease diagnosis and drug delivery. The combination of Fe3O4 with biocompatible polymers to produce smart drug delivery systems for use in pharmaceutical formulation present a powerful tool to target anti-cancer drugs to specific tumor sites through the application of an external magnetic field. In the present study, we focused on the evaluation of the effect of the magnetic field application time on the rate of drug release from iron oxide polymeric nanoparticles. Doxorubicin, an anticancer drug, was selected as the model drug loaded into the nanoparticles. Nanoparticles composed of poly(d-lactide-co-glycolide (PLGA), a biocompatible polymer already approved by FDA, containing iron oxide nanoparticles (MNP) for magnetic targeting and doxorubicin (DOX) were synthesized by the o/w solvent extraction/evaporation method and characterized by scanning electron microscopy (SEM), by dynamic light scattering (DLS), by inductively coupled plasma-atomic emission spectrometry and by Fourier transformed infrared spectroscopy. The produced particles yielded smooth surfaces and spherical shapes exhibiting a size between 400 and 600 nm. The effect of the magnetic doxorubicin loaded PLGA nanoparticles produced on cell viability was investigated in mammalian CHO cell cultures. The results showed that unloaded magnetic PLGA nanoparticles were nontoxic while the magnetic particles without polymeric coating show a high level of toxicity. Concerning the therapeutic activity doxorubicin loaded magnetic particles cause a remarkable enhancement of the cell inhibition rates compared to their non-magnetic counterpart. In vitro drug release studies performed under a non-permanent magnetic field show that the application time and the on/off cycle duration have a great influence with respect to the final amount and to the rate of drug release. In order to determine the mechanism of drug release, the data obtained from the release curves were fitted to the semi-empirical equation of the the Korsmeyer-Peppas model that may be used to describe the Fickian and non-Fickian release behaviour. Doxorubicin release mechanism has shown to be governed mainly by Fickian diffusion. The results obtained show that the rate of drug release from the produced magnetic nanoparticles can be modulated through the magnetic field time application.

Keywords: drug delivery, magnetic nanoparticles, PLGA nanoparticles, controlled release rate

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Authors: Zenah Gheblawi, Susan Armijo-Olivo, Elisa B. Pelai, Vaishali Sharma, Musa Tashfeen, Angela Fung, Francisca Claveria

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Due to physiological differences between men and women, pain is experienced differently between the two sexes. Chronic pain disorders, notably temporomandibular disorders (TMDs), disproportionately affect women in diagnosis, and pain severity in opposition of their male counterparts. TMDs are a type of musculoskeletal disorder that target the masticatory muscles, temporalis muscle, and temporomandibular joints, causing considerable orofacial pain which can usually be referred to the neck and back. Therapeutic methods are scarce, and are not TMD-centered, with the latest research suggesting that subjects with chronic musculoskeletal pain disorders have abnormal alterations in the grey matter of their brains which can be remedied with exercise, and thus, decreasing the pain experienced. The aim of the study is to investigate the effects of exercise therapy in TMD female patients experiencing chronic jaw pain and to assess the consequential effects on brain activity. In a randomized controlled trial, the effectiveness of an exercise program to improve brain alterations and clinical outcomes in women with TMD pain will be tested. Women with chronic TMD pain will be randomized to either an intervention arm or a placebo control group. Women in the intervention arm will receive 8 weeks of progressive exercise of motor control training using visual feedback (MCTF) of the cervical muscles, twice per week. Women in the placebo arm will receive innocuous transcutaneous electrical nerve stimulation during 8 weeks as well. The primary outcomes will be changes in 1) pain, measured with the Visual Analogue Scale, 2) brain structure and networks, measured by fractional anisotropy (brain structure) and the blood-oxygen level dependent signal (brain networks). Outcomes will be measured at baseline, after 8 weeks of treatment, and 4 months after treatment ends and will determine effectiveness of MCTF in managing TMD, through improved clinical outcomes. Results will directly inform and guide clinicians in prescribing more effective interventions for women with TMD. This study is underway, and no results are available at this point. The results of this study will have substantial implications on the advancement in understanding the scope of plasticity the brain has in regards with pain, and how it can be used to improve the treatment and pain of women with TMD, and more generally, other musculoskeletal disorders.

Keywords: exercise therapy, musculoskeletal disorders, physical therapy, rehabilitation, tempomandibular disorders

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Authors: A. Gramza-Michałowska, J. Skręty, M. Antczak, J. Kobus-Cisowska, D. Kmiecik, J. Korczak, Kulczyński Bartosz

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Background: Modern consumer highly appreciates the correlation between eating habits and health. Intensified research showed many proofs confirming that food besides its basic nutritional function, possess also significant prophylactic and therapeutic potential. Preventive potential of selected food is commonly used as improvement factor of patients life standard. World Health Organization indicates that diabetes (Diabetes mellitus) and obesity are two of the most common and dangerous diseases. Diet therapy is an element of diabetes education program and a part of healing process, allowing maintaining and remaining the optimal metabolic state of the system. It must be remembered that diabetes treatment should be individualized to each patient. One of highly recommended vegetable for diabetes is asparagus (Asparagus officinalis L.), low calories common plant, growing in European countries. Objective: To propose the technology of unsweetened muesli production with addition of new components, we investigated the effects of selected vegetable addition on antioxidative capacity and consumer’s acceptance of muesli as representative of breakfast product. Methods: Muesli was formulated from a composition of oat flakes, flaxseed, bran, carrots, broccoli and asparagus. Basic composition of muesli was evaluated as content of protein, lipids, fatty acid composition, ash, selected minerals and caloricity. Antioxidant capacity of muesli was evaluated with use radical scavenging methods (DPPH, ABTS), ORAC value and PCL - photochemiluminescence antiradical potential. Proposed muesli as new product was also characterized with sensory analysis, which included color, scent, taste, consistency and overall acceptance of a product. Results: Results showed that addition of freeze-dried asparagus into muesli allowed to lower the fat content and caloricity of a product according to the base product. No significant loss in antioxidant potential was evaluated, also the sensory value of a product was not negative. Conclusion: Designed muesli would be an answer for obese people looking for healthy snack during the daytime. Results showed that product with asparagus addition would be accepted by the consumers and because of its antidiabetic potential could be a n important factor in prevention of diabetes or obesity. Financial support by the UE Project no PO IG 01.01.00.00-061/09

Keywords: muesli, vegetables, asparagus, antioxidant potential, lipids

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Authors: N. Khursheed, M. Fatima, S. Jamal, A. Raza, S. Rattani, Q. Ahsan, A. Rasheed, M. Jawed

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Introduction: Antibiotics are among the commonly prescribed medicines to treat bacterial infections. Their misuse intensifies resistance, and overuse incurs heavy losses to the healthcare system in terms of increased treatment costs and enhanced disease burden. Studies show that 40% of empirically used antibiotics are irrationally utilized. The objective of this study was to evaluate prescribing pattern of antibiotics at six public sector tertiary care hospitals across Pakistan. Methods: A multicenter cross-sectional point prevalence survey (PPS) was conducted in selected wards of six public sector tertiary care hospitals in Pakistan as part of the Clinical Engagement program by Fleming Fund Country Grant Pakistan in collaboration with Indus Hospital & Health Network (IHHN) from February to March 2021, these included Jinnah Postgraduate Medical Center and Dr. Ruth K. M. Pfau Civil Hospital from Karachi, Sheikh Zayed Hospital Lahore, Nishtar Medical University Hospital Multan, Medical Teaching Institute Hayatabad Medical Complex Peshawar, and Provincial Headquarters Hospital Gilgit. WHO PPS methodology was used for data collection (Hospital, ward, and patient level data was collected). Data was entered into the open-source Kobo Collect application and was analyzed using SPSS (version 22.0). Findings: Medical records of 837 in-patients were surveyed, of which the prevalence of antibiotics use was 78.5%. The most commonly prescribed antimicrobial was Ceftriaxone (21.7%) which is categorized in the Watch group of WHO AWaRe Classification, followed by Metronidazole (17.3%), Cefoperazone/Sulbactam (8.4%), Co-Amoxiclav (6.3%) and Piperacillin/Tazobactam (5.9%). The antibiotics were prescribed largely for surgical prophylaxis (36.7%), followed by community-acquired infections (24.7%). One antibiotic was prescribed to 46.7%, two to 39.9%, and three or more to 12.5 %. Two of six (30%) hospitals had functional drug and therapeutic committees, three (50%) had infection prevention and control committees, and one facility had an antibiotic formulary. Conclusion: Findings demonstrate high consumption of broad-spectrum antimicrobials and emphasizes the importance of expanding the antimicrobial stewardship program. Mentoring clinical teams will help to rationalize antimicrobial use.

Keywords: antimicrobial resistance, antimicrobial stewardship, point prevalence survey, antibiotics

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Authors: Donna Banks

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In 1998 Winston James called for more research on the Caribbean diaspora and this ethnographic study, incorporating participant observation, interviews, and archival research, adds to the scholarship in this area. The research is grounded in the discipline of cultural studies but is cross-disciplinary in nature, engaging anthropology, psychology, and urban planning. This paper centers on community murals and their contribution to a more culturally diverse and representative community. While many museums are in the process of reassessing their collection, acquiring works, and developing programming to be more inclusive, and public art programs are investing millions of dollars in trying to fashion an identity in which all residents can feel included, local artists in neighborhoods in many countries have been using community murals to tell their stories. Community murals serve a historical, political, and social purpose and are an instrumental strategy in creative placemaking projects. Community murals add to the livability of an area. Even though official measurements of livability do not include race, ethnicity, and gender - which are egregious omissions - murals are a way to integrate historically underrepresented people into the wider history of a country. This paper draws attention to a creative placemaking project in the port city of Bristol, England. A city, like many others, with a history of spacializing race and racializing space. For this reason, Bristol’s Seven Saints of St. Pauls® Art & Heritage Trail, which memorializes seven Caribbean-born social and political change agents, is examined. The Seven Saints of St. Pauls® Art & Heritage Trail is crucial to the city, as well as the country, in its contribution to the de-racialization of public spaces. Within British art history, with few exceptions, portraits of non-White people who are not depicted in a subordinate role have been absent. The artist of the mural project, Michelle Curtis, has changed this long-lasting racist and hegemonic narrative. By creating seven large-scale portraits of individuals not typically represented visually, the artist has added them into Britain’s story. In these murals, however, we see more than just the likeness of a person; we are presented with a visual commentary that reflects each Saint’s hybrid identity of being both Black Caribbean and British, as well as their social and political involvement. Additionally, because the mural project is part of a heritage trail, the murals' are therapeutic and contribute to improving the well-being of residents and strengthening their sense of belonging.

Keywords: belonging, murals, placemaking, representation

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Authors: Michio Kurosu

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Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

Procedia PDF Downloads 49

Authors: Shao-Ying Wang, Shin-I Shih, Chi-Cheng Wu

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Background: By following to the maturity theory about age, the manifestation of depression in different age groups under occupational stressors still remains unclear. Therefore, the aim of this study was to examine the depression within four main symptoms clusters: cognition, affect, physical complaints and interpersonal difficulty among the different age groups. Additionally, this study also used the stress appraisal theory, through the examination of challenge and hindrance appraisals, the effects of cognitive factors were expected to give therapeutic indication for the future treatment of depression under abusive leadership. Methods (Participants and Procedure): The data were collected in two waves from employees of local companies in Taiwan. The participants (58 males and 167 females) were native Chinese speakers, ranging in age from 20 to 59 years (M= 36.51). Up to 80% educational level of participants were above senior high. The married population was approximately at 43%. Measures; 1. Abusive Leadership: To measure abusive leadership, we used 15-item scale of abusive supervision which anchored on a 7-point Likert-type scale. (α= .96) 2. Depression: We used Taiwanese Depression Scale to measure the 4 clusters (cognition, affect, physical complaints and interpersonal difficulty) of symptoms. Participants responded for depression anchored on a 7-point Likert-type scale (α= .96). 3. Stress Appraisal Scale: To measure challenge and hindrance types of appraisal, participants responded to 33-item measure anchored on a 7-point Likert-type scale. (Challenge appraisal; α= .90; hindrance appraisal α= .87). Results: The results of correlation showed that there was a significant and negative correlation between abusive leadership and age (r = - .21, p < .01). Abusive leadership was positive correlated significantly with hindrance appraisal (r = .52, p < .01) and depression (r = .20, p < .01). The results also showed that hindrance appraisal was correlated to depression positively (r = .36, p < .01). A one-way ANOVA was conducted to compare the effect of lower/middle/order age groups on each cluster of depressive symptoms. The results showed that the effect of age groups on cognition was significant F (2, 157) =3.66, P < .05. Older age group (M=13.43 SD=6.84) reported less cognitive symptoms of depression than the middle (M=16.77 SD=7.49) and lower age (M=16.91 SD=6.97) groups. Besides, the effect of age groups on affect was also significant F (2,157)= 4.09 P < .05. Older age group (M=18.68 SD=8.98) reported less affective symptoms of depression than the middle (M=22.01 SD=7.96) and lower age (M=23.56 SD=7.67) groups. Moreover, the main effect of hindrance appraisal was found F (2, 157) =3.81, P < .05. Older age group (M=9.44 SD=2.89) reported fewer score on hindrance appraisals than the middle (M=11.06 SD=4.02) and lower age (M=9.62 SD=3.17) groups. To conclude, the severity of depression symptoms varies across different age groups. Maturity seems to be the protective factor to depression, accompanying with lower hindrance appraisals.

Keywords: abusive leadership, affective commitment, depression symptoms, psychological well-being

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Authors: Yihenew Simegniew Birhan, Hsieh Chih Tsai

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The recent advancements in synthetic chemistry and nanotechnology fostered the development of different nanocarriers for enhanced intracellular delivery of pharmaceutical agents to tumor cells. Polymeric micelles (PMs), characterized by small size, appreciable drug loading capacity (DLC), better accumulation in tumor tissue via enhanced permeability and retention (EPR) effect, and the ability to avoid detection and subsequent clearance by the mononuclear phagocyte (MNP) system, are convenient to improve the poor solubility, slow absorption and non-selective biodistribution of payloads embedded in their hydrophobic cores and hence, enhance the therapeutic efficacy of chemotherapeutic agents. Recently, redox-responsive polymeric micelles have gained significant attention for the delivery and controlled release of anticancer drugs in tumor cells. In this study, we synthesized redox-responsive diselenide bond containing amphiphilic polymer, Bi(mPEG-PLGA)-Se₂ from mPEG-PLGA, and 3,3'-diselanediyldipropanoic acid (DSeDPA) using DCC/DMAP as coupling agents. The successful synthesis of the copolymers was verified by different spectroscopic techniques. Above the critical micelle concentration, the amphiphilic copolymer, Bi(mPEG-PLGA)-Se₂, self-assembled into stable micelles. The DLS data indicated that the hydrodynamic diameter of the micelles (123.9 ± 0.85 nm) was suitable for extravasation into the tumor cells through the EPR effect. The drug loading content (DLC) and encapsulation efficiency (EE) of DOX-loaded micelles were found to be 6.61 wt% and 54.9%, respectively. The DOX-loaded micelles showed initial burst release accompanied by sustained release trend where 73.94% and 69.54% of encapsulated DOX was released upon treatment with 6mM GSH and 0.1% H₂O₂, respectively. The biocompatible nature of Bi(mPEG-PLGA)-Se₂ copolymer was confirmed by the cell viability study. In addition, the DOX-loaded micelles exhibited significant inhibition against HeLa cells (44.46%), at a maximum dose of 7.5 µg/mL. The fluorescent microscope images of HeLa cells treated with 3 µg/mL (equivalent DOX concentration) revealed efficient internalization and accumulation of DOX-loaded Bi(mPEG-PLGA)-Se₂ micelles in the cytosol of cancer cells. In conclusion, the intelligent, biocompatible, and the redox stimuli-responsive behavior of Bi(mPEG-PLGA)-Se₂ copolymer marked the potential applications of diselenide-linked mPEG-PLGA micelles for the delivery and on-demand release of chemotherapeutic agents in cancer cells.

Keywords: anticancer drug delivery, diselenide bond, polymeric micelles, redox-responsive

Procedia PDF Downloads 89

Authors: R. Zhankina, U. Zhanbyrbekuly, A. Tamadon, M. Askarov, R. Sherkhanov, D. Akhmetov, D. Saipiyeva, N. Keulimzhaev

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Male infertility affects about 15% of couples of reproductive age. Approximately 10–15% have azoospermia who have previously been diagnosed with male infertility. Azoospermia is regarded as the absence of spermatozoa in the ejaculate and is found in 10-15% of infertile men. Non-obstructive azoospermia is considered a cause of male infertility that is not amenable to drug therapy. Patients with non-obstructive azoospermia are unable to have their "own" children and have only options for adoption or use of donor sperm. Advances in assisted reproductive technologies such as intracytoplasmic sperm injection in vitro fertilization have significantly changed the management of patients with non-obstructive azoospermia. Advances in biotechnology have increased the options for treating patients with non-obstructive azoospermia. Mesenchymal stem cell therapy has been recognized as a new option for infertility treatment. Material and methods of the study: After obtaining informed consent, 5 patients diagnosed with non-obstructive azoospermia were included in an open, non-randomized study. The age of the patients ranged from 24 to 35 years. The examination was carried out before the start of treatment, which included biochemical blood tests, hormonal profile levels (luteinizing hormone, follicle-stimulating hormone, testosterone, prolactin, inhibin B); tests for tumor markers; genetic research. All studies were carried out in compliance with the requirements of Protocol No. 8 dated 06/09/20, approved by the Local Ethical Commission of NJSC "Astana Medical University". The control examination of patients was carried out after 6 months, by re-taking the program and hormonal profile (testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, inhibin B). Before micro-TESE of the testis, all 5 patients underwent myeloexfusion in the operating room. During the micro-TESE, autotransplantation of mesenchymal stem cells into the testicular network, previously cultured in a cell technology laboratory for 2 weeks, was performed. Results of the study: in all patients, the levels of total testosterone increased, the level of follicle-stimulating hormone decreased, the levels of luteinizing hormone returned to normal, the level of inhibin B increased. IVF with a positive result; another patient (20%) had spermatogenesis cells. Non-obstructive azoospermia and mesenchymal stem cells Conclusions: The positive results of this work serve as the basis for the application of a new cellular therapeutic approach for the treatment of non-obstructive azoospermia using mesenchymal stem cells.

Keywords: cell therapy, regenerative medicine, male infertility, mesenchymal stem cells

Procedia PDF Downloads 93

Authors: Gizaw Mamo Gebeyehu, Marianna Pap, Geza Makkai, Tibor Z. Janosi, Shima Rashidian, Tibor A. Rauch

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Sepsis poses a significant global health threat, necessitating extensive exploration of indicators tied to its pathological mechanisms and multi-organ dysfunction. While murine studies have shed light on sepsis, the intricate cellular and molecular landscape in human sepsis remains enigmatic. Exploring the influence of activated monocyte-derived exosomes in sepsis sheds light on a promising pathway for understanding the intricate cellular and molecular mechanisms involved in this condition in humans. In sepsis, exosome-borne mRNA and miRNA orchestrate immune response gene expression in recipient cells. Yet, the specifics of exosome-mediated cell-to-cell communication, especially how mRNA cargoes modulate gene expression in recipient cells, remain poorly understood. This study aims to elucidate the precise molecular pathways through which exosomal mRNA cargo, particularly MAFB, contributes to the developing sepsis-induced molecular aberrations in liver tissues, employing rigorously defined cell culture conditions. THP-1 cells were treated with LPS to induce changes in exosomal RNA profiles. Exosomes were isolated and characterized using microscopy and mass spectrometry. RNA was extracted from exosomes and sequenced. The most abundant exosomal mRNAs were subjected to GO analysis for functional annotation analysis and KEGG database analysis to identify the involved enriched pathways. PCR (Polymerase Chain Reaction), RNA sequencing, and Western blotting were involved to analyze changes in gene expression, protein levels, and signaling pathways within the liver cells( HepG2) after exposure to exosomal MAFB. This study pinpoints exosomal MAFB as a potential key regulator linked to liver cell damage during sepsis, along with associated genes (miR155HG, H3F3A, and possibly JARD2) forming a crucial molecular pathway contributing to liver cell injury, Together, these elements indicate a vital molecular pathway that plays a significant role in the emergence of liver cell injury during sepsis.. These findings suggest the importance of further research on these components for potential therapeutic interventions in managing acute liver damage in sepsis.

Keywords: sepsis, exososome, exosomal MAFB, LPS-induced THP-1 cells, RNA profiles, sepsis-triggered liver injury

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Authors: Emma Plante, Charles Ekwunwa, Diego Illanes

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Introduction: Serum Sickness-Like Reaction (SSLR) is an inflammatory immune response characterized by a rash, polyarthralgias, and fever. SSLR usually occurs in response to a new medication (most commonly antibiotics, anticonvulsants, or antiinflammatory agents) and is believed to involve the formation of drug-specific immune complexes. Here we present a case of a 16-year-old female patient who developed an SSLR in response to the D-mannose-containing over-the-counter supplement, Uqora, used to promote bladder health. Methodology: The methodology for this study included a thorough literature search for other cases of SSLR associated with D-Mannose containing products. Data collection was performed through a review of the patient’s medical record, including history, physical examination, relevant laboratory results, and treatment plan. Findings: A 16-year-old female with a history of overactive bladder and anemia presented with a diffuse urticarial rash, headaches, joint pain, and swelling for three days. Her medications included oral contraceptive pills, iron, mirabegron, UQora, and a probiotic. Physical examination revealed a diffuse urticarial rash, and her musculoskeletal exam revealed swelling and tenderness in her wrists. Her CBC, basic metabolic panel, liver function panel, lyme titers, and urinalysis were all within normal limits. The patient was referred to an allergist, who diagnosed her with SSLR. All medications were discontinued, and she was treated with a 7-day course of prednisone and cetirizine. Her symptoms resolved, and her medications were slowly resumed sequentially over several months. However, UQora triggered a recurrence of her symptoms, and it was identified as the culprit medication. Consequently, UQora was permanently discontinued, and the patient has remained symptom-free. Conclusion: This case report describes the first documented case of SSLR caused by UQora (active ingredient D-mannose). D-Mannose is a monosaccharide found in many plants and fruits, and it is commonly used to prevent urinary tract infections. While the clinical features and timeline, in this case, were typical of SSLR, UQora as the trigger was highly unusual. Clinicians should be aware of the diverse triggers of SSLR and the importance of prompt identification and management to enhance patient safety. It is possible D-mannose was not the trigger, and further research is necessary to better understand the potential therapeutic applications of D-mannose, as well as the potential risks and interactions.

Keywords: serum sickness-like reaction, d-mannose, hypersensitivity reaction, urticaria

Procedia PDF Downloads 62

Authors: Randa M. T. Mohamed

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Spices have long been used as traditional ingredients in the kitchen for seasoning, coloring, aromatic and food preservative properties. Besides, spices are equally used for therapeutic purposes. The objective of this study was to survey and document the medicinal properties of spices commonly used in the Sudanese kitchen for different food preparations. Also, extracts from reported spices were screened for the presence of secondary metabolites as well as their antioxidant and beta-lactamase inhibitory properties. This study was conducted in the Rekabbya Quartier in Omdurman, Khartoum State, Sudan. Information was collected by carrying out semi-structured interviews. All informants (30) in the present study were women. Spices were purchased from Attareen shop in Omdurman. Essential oils from spices were extracted by hydrodistillation and ethanolic extracts by maceration. Phytochemical screening was performed by thin layer chromatography (TLC). The antioxidant capacity of essential oils and ethanolic extracts was investigated through TLC bioautography. Beta lactamase inhibitory activity was performed by the acidimetric test. Ethnobotany study showed that a total of 16 spices were found to treat 36 ailments belonging to 10 categories. The most frequently claimed medicinal uses were for the digestive system diseases treated by 14 spices and respiratory system diseases treated by 8 spices. Gynaecological problems were treated by 4 spices. Dermatological diseases were cured by 5 spices while infections caused by tapeworms and other microbes causing dysentery were treated by 3 spices. 4 spices were used to treat bad breath, bleeding gum and toothache. Headache, eyes infection, cardiac stimulation and epilepsy were treated by one spice each. Other health problem like fatigue and loss of appetite and low breast milk production were treated by 1, 3 and 2 spices respectively. The majority (69%, 11/16) of spices were exported from different countries like India, China, Indonesia, Ethiopia, Egypt and Nigeria while 31% (5/16) was cultivated in Sudan. Essential oils of all spices were rich in terpenes while ethanolic extracts contained variable classes of secondary metabolites. Both essential oils and ethanolic extracts of all spices exerted considerable antioxidant activity. Only one extract, Syzygium aromaticum, possessed beta lactamase inhibitory activity. In conclusion, this study could contribute in conserving information on traditional medicinal uses of spices in Sudan. Also, the results demonstrated the potential of some of these spices to exert beneficial antimicrobial and antioxidant effect. Detailed phytochemical and biological assays of these spices are recommended.

Keywords: spices, ethnobotany, phytoconstituents, antioxidant, beta lactamase inhibition

Procedia PDF Downloads 46

Authors: Beom-Seok Ko, Yoo-Seok Kim, Woo-Sung Lim, Ku-Sang Kim, Hyun-Ah Kim, Jin-Sun Lee, An-Bok Lee, Jin-Gu Bong, Tae-Hyun Kim, Sei-Hyun Ahn

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Background: Breast conserving surgery (BCS) followed by radiation therapy is today standard therapy for early breast cancer. It is safe therapeutic procedure in early breast cancers, because it provides the same level of overall survival as mastectomy. There are a number of different types of incisions used to BCS. Avoiding scars on the breast is women’s desire. Numerous minimal approaches have evolved due to this concern. Periareolar incision is often used when the small tumor relatively close to the nipple. But periareolar incision has a disadvantages include limited exposure of the surgical field. In plastic surgery, various methods such as zigzag incisions have been recommended to achieve satisfactory esthetic results. Periareolar zigzag incision has the advantage of not only good surgical field but also contributed to better surgical scars. The purpose of this study was to evaluate the oncological safety of procedures by studying the status of the surgical margins of the excised tumor specimen and reduces the need for further surgery. Methods: Between January 2016 and September 2016, 148 women with breast cancer underwent BCS or mastectomy by the same surgeon in ASAN medical center. Patients with exclusion criteria were excluded from this study if they had a bilateral breast cancer or underwent resection of the other tumors or taken axillary dissection or performed other incision methods. Periareolar zigzag incision was performed and excision margins of the specimen were identified frozen sections and paraffin-embedded or permanent sections in all patients in this study. We retrospectively analyzed tumor characteristics, the operative time, size of specimen, the distance from the tumor to nipple. Results: A total of 148 patients were reviewed, 72 included in the final analysis, 76 excluded. The mean age of the patients was 52.6 (range 25-19 years), median tumor size was 1.6 cm (range, 0.2-8.8), median tumor distance from the nipple was 4.0 cm (range, 1.0-9.0), median excised specimen sized was 5.1 cm (range, 2.8-15.0), median operation time was 70.0 minute (range, 39-138). All patients were discharged with no sign of infection or skin necrosis. Free resection margin was confirmed by frozen biopsy and permanent biopsy in all samples. There were no patients underwent reoperation. Conclusions: We suggest that periareolar zigzag incision can provide a good surgical field to remove a relatively large tumor and may provide cosmetically good outcomes.

Keywords: periareolar zigzag incision, breast conserving surgery, breast cancer, resection margin

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Authors: Danni Cheng

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Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

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Authors: Christopher R. Triggle, Hong Ding, Khaled Machaca, Gnanapragasam Arunachalam

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The antidiabetic drug, metformin, has been in clinical use for over 50 years and remains the first choice drug for the treatment of type two diabetes. In addition to its effectiveness as an oral anti-hyperglycaemic drug metformin also possesses vasculoprotective effects that are assumed to be secondary to its ability to reduce insulin resistance and control glycated hemoglobin levels; however, recent data from our laboratory indicate that metformin also has direct vasoprotective effects that are mediated, at least in part, via the anti-ageing gene, SIRT1. Diabetes is a major risk factor for the development of cardiovascular disease (CVD) and it is also well established that tobacco use further enhances the risk of CVD; however, it is not known whether treatment with metformin can offset the negative effects of diabetes and tobacco use on cardiac function. The current study was therefore designed to investigate 1: the effects of hyperglycaemia (HG) either alone or in the presence of elevated fatty acids (palmitate) and nicotine on the protein expression levels of the deacetylase sirtuin 1 (the protein product of SIRT1), anti-apoptotic Bcl-2, pro-apoptotic BIM and the pro-apoptotic, tumour suppressor protein, acetylated p53 in cardiomyocytes. 2: the ability of metformin to prevent the detrimental effects of HG, palmitate and nicotine on cardiomyocyte survival. Cell culture protocols were designed using a rat cardiomyocyte cell line, H9c2, either under normal glycaemic (NG) conditions of 5.5mM glucose, or hyperglycaemic conditions (HG) of 25mM glucose with, or without, added palmitate (250μM) or nicotine (1.0mM) for 24h. Immuno-blotting was used to detect the expression of sirtuin 1, Bcl-2, BIM, acetylated (Ac)-p53, p53 with β-actin used as the reference protein. Exposure to HG, palmitate, or nicotine alone significantly reduced expression of sirtuin1, Bcl-2 and raised the expression levels of acetylated p53 and BIM; however, the combination of HG, palmitate and nicotine had a synergistic effect to significantly suppress the expression levels of sirtuin 1 and Bcl-2, but further enhanced the expression of Ac-p53, and BIM. The inclusion of 1000μM, but not 50μM, metformin in the H9c2 cell culture protocol prevented the effects of HG, palmitate and nicotine on the pro-apoptotic pathways. Collectively these data indicate that metformin, in addition to its anti-hyperglycaemic and vasculoprotective properties, also has direct cardioprotective actions that offset the negative effects of hyerglycaemia, elevated free fatty acids and nicotine on cardiac cell survival. These data are of particular significance for the treatment of patients with diabetes who are also smokers as the inclusion of metformin in their therapeutic treatment plan should help reduce cardiac-related morbidity and mortality.

Keywords: apoptosis, cardiac muscle, diabetes, metformin, nicotine

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Authors: Anjali Roy, Mirza S. Baig

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Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid rich plaque enriched with necrotic core, modified lipid accumulation, smooth muscle cells, endothelial cells, leucocytes and macrophages. Macrophage foam cells play a critical role in the occurrence and development of inflammatory atherosclerotic plaque. Foam cells are the fat-laden macrophages in the initial stage atherosclerotic lesion formation. Foam cells are an indication of plaque build-up, or atherosclerosis, which is commonly associated with increased risk of heart attack and stroke as a result of arterial narrowing and hardening. The mechanisms that drive atherosclerotic plaque progression remain largely unknown. Dissecting the molecular mechanism involved in process of macrophage foam cell formation will help to develop therapeutic interventions for atherosclerosis. To investigate the mechanism, we studied the role of nitric oxide synthase 1(NOS1)-mediated nitric oxide (NO) on low-density lipoprotein (LDL) uptake by bone marrow derived macrophages (BMDM). Using confocal microscopy, we found that incubation of macrophages with NOS1 inhibitor, TRIM (1-(2-Trifluoromethylphenyl) imidazole) or L-NAME (N omega-nitro-L-arginine methyl ester) prior to LDL treatment significantly reduces the LDL uptake by BMDM. Further, addition of NO donor (DEA NONOate) in NOS1 inhibitor treated macrophages recovers the LDL uptake. Our data strongly suggest that NOS1 derived NO regulates LDL uptake by macrophages and foam cell formation. Moreover, we also checked proinflammatory cytokine mRNA expression through real time PCR in BMDM treated with LDL and copper oxidized LDL (OxLDL) in presences and absences of inhibitor. Normal LDL does not evoke cytokine expression whereas OxLDL induced proinflammatory cytokine expression which significantly reduced in presences of NOS1 inhibitor. Rapid NOS-1-derived NO and its stable derivative formation act as signaling agents for inducible NOS-2 expression in endothelial cells, leading to endothelial vascular wall lining disruption and dysfunctioning. This study highlights the role of NOS1 as critical players of foam cell formation and would reveal much about the key molecular proteins involved in atherosclerosis. Thus, targeting NOS1 would be a useful strategy in reducing LDL uptake by macrophages at early stage of disease and hence dampening the atherosclerosis progression.

Keywords: atherosclerosis, NOS1, inflammation, oxidized LDL

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Authors: Adriana De Serio, Adrian Korek

Abstract:

Aims: This experiential research work presents a Group-MusicTherapy-Theatre-Plan (MusThePlan) the authors have carried out to support the actors. The MusicTherapy gives rise to individual psychophysical feedback and influences the emotional centres of the brain and the subconsciousness. Therefore, the authors underline the effectiveness of the preventive, educational, and training goals of the MusThePlan to lead theatre students and actors to deal with anxiety and to overcome psychophysical weaknesses, shyness, emotional stress in stage performances, to increase flexibility, awareness of one's identity and resources for a positive self-development and psychophysical health, to develop and strengthen social bonds, increasing a network of subjects working for social inclusion and reduction of stigma. Materials-Methods: Thirty students from the University Theatre Faculty participated in weekly music therapy sessions for two months; each session lasted 120 minutes. MusThePlan: Each session began with a free group rhythmic-sonorous-musical-production by body-percussion, voice-canto, instruments, to stimulate communication. Then, a synchronized-structured bodily-rhythmic-sonorous-musical production also involved acting, dances, movements of hands and arms, hearing, and more sensorial perceptions and speech to balance motor skills and the muscular tone. Each student could be the director-leader of the group indicating a story to inspire the group's musical production. The third step involved the students in rhythmic speech and singing drills and in vocal exercises focusing on the musical pitch to improve the intonation and on the diction to improve the articulation and lead up it to an increased intelligibility. At the end of each musictherapy session and of the two months, the Musictherapy Assessment Document was drawn up by analysis of observation protocols and two Indices by the authors: Patient-Environment-Music-Index (time to - tn) to estimate the behavior evolution, Somatic Pattern Index to monitor subject’s eye and mouth and limb motility, perspiration, before, during and after musictherapy sessions. Results: After the first month, the students (non musicians) learned to play percussion instruments and formed a musical band that played classical/modern music on the percussion instruments with the musictherapist/pianist/conductor in a public concert. At the end of the second month, the students performed a public musical theatre show, acting, dancing, singing, and playing percussion instruments. The students highlighted the importance of the playful aspects of the group musical production in order to achieve emotional contact and harmony within the group. The students said they had improved kinetic and vocal and all the skills useful for acting activity and the nourishment of the bodily and emotional balance. Conclusions: The MusThePlan makes use of some specific MusicTherapy methodological models, techniques, and strategies useful for the actors. The MusThePlan can destroy the individual "mask" and can be useful when the verbal language is unable to undermine the defense mechanisms of the subject. The MusThePlan improves actor’s psychophysical activation, motivation, gratification, knowledge of one's own possibilities, and the quality of life. Therefore, the MusThePlan could be useful to carry out targeted interventions for the actors with characteristics of repeatability, objectivity, and predictability of results. Furthermore, it would be useful to plan a University course/master in “MusicTherapy for the Theatre”.

Keywords: musictherapy, sonorous-musical energy, quality of life, theatre

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Authors: Terefe Fuge, George Tsourtos , Emma Miller

Abstract:

Objectives: Maintaining optimal adherence and viral suppression in people living with HIV (PLWHA) is essential to ensure both preventative and therapeutic benefits of antiretroviral therapy (ART). Prisoners bear a particularly high burden of HIV infection and are highly likely to transmit to others during and after incarceration. However, the level of adherence and viral suppression, as well as its associated factors in incarcerated populations in low-income countries is unknown. This study aimed to determine the prevalence of non-adherence and viral failure, and contributing factors to this amongst prisoners in South Ethiopia. Methods: A prospective cohort study was conducted between June 1, 2019 and July 31, 2020 to compare the level of adherence and viral suppression between incarcerated and non-incarcerated PLWHA. The study involved 74 inmates living with HIV (ILWHA) and 296 non-incarcerated PLWHA. Background information including sociodemographic, socioeconomic, psychosocial, behavioural, and incarceration-related characteristics was collected using a structured questionnaire. Adherence was determined based on participants’ self-report and pharmacy refill records, and plasma viral load measurements which were undertaken within the study period were prospectively extracted to determine viral suppression. Various univariate and multivariate regression models were used to analyse data. Results: Self-reported dose adherence was approximately similar between ILWHA and non-incarcerated PLWHA (81% and 83% respectively), but ILWHA had a significantly higher medication possession ratio (MPR) (89% vs 75%). The prevalence of viral failure (VF) was slightly higher (6%) in ILWHA compared to non-incarcerated PLWHA (4.4%). The overall dose non-adherence (NA) was significantly associated with missing ART appointments, level of satisfaction with ART services, patient’s ability to comply with a specified medication schedule and types of methods used to monitor the schedule. In ILWHA specifically, accessing ART services from a hospital compared to a health centre, an inability to always attend clinic appointments, experience of depression and a lack of social support predicted NA. VF was significantly higher in males, people of age 31-35 years and in those who experienced social stigma, regardless of their incarceration status. Conclusions: This study revealed that HIV-infected prisoners in South Ethiopia were more likely to be non-adherent to doses and so to develop viral failure compared to their non-incarcerated counterparts. A multitude of factors was found to be responsible for this requiring multilevel intervention strategies focusing on the specific needs of prisoners.

Keywords: Adherence , Antiretroviral therapy, Incarceration, South Ethiopia, Viral suppression

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Authors: Hsiang-Ru Lin

Abstract:

Cholesterol plays an essential role in the regulation of the progression of numerous important diseases including atherosclerosis and Alzheimer disease so the generation of suitable cholesterol-lowering reagents is urgent to develop. Liver X receptor (LXR) is a ligand-activated transcription factor whose natural ligands are cholesterols, oxysterols and glucose. Once being activated, LXR can transactivate the transcription action of various genes including CYP7A1, ABCA1, and SREBP1c, involved in the lipid metabolism, glucose metabolism and inflammatory pathway. Essentially, the upregulation of ABCA1 facilitates cholesterol efflux from the cells and attenuates the production of beta-amyloid (ABeta) 42 in brain so LXR is a promising target to develop the cholesterol-lowering reagents and preventative treatment of Alzheimer disease. Engelhardia roxburghiana is a deciduous tree growing in India, China, and Taiwan. However, its chemical composition is only reported to exhibit antitubercular and anti-inflammatory effects. In this study, four compounds, engelheptanoxides A, C, engelhardiol A, and B isolated from the root of Engelhardia roxburghiana were evaluated for their agonistic activity against LXR by the transient transfection reporter assays in the HepG2 cells. Furthermore, their interactive modes with LXR ligand binding pocket were generated by molecular modeling programs. By using the cell-based biological assays, engelheptanoxides A, C, engelhardiol A, and B showing no cytotoxic effect against the proliferation of HepG2 cells, exerted obvious LXR agonistic effects with similar activity as T0901317, a novel synthetic LXR agonist. Further modeling studies including docking and SAR (structure-activity relationship) showed that these compounds can locate in LXR ligand binding pocket in the similar manner as T0901317. Thus, LXR is one of nuclear receptors targeted by pharmaceutical industry for developing treatments of Alzheimer and atherosclerosis diseases. Importantly, the cell-based assays, together with molecular modeling studies suggesting a plausible binding mode, demonstrate that engelheptanoxides A, C, engelhardiol A, and B function as LXR agonists. This is the first report to demonstrate that the extract of Engelhardia roxburghiana contains LXR agonists. As such, these active components of Engelhardia roxburghiana or subsequent analogs may show important therapeutic effects through selective modulation of the LXR pathway.

Keywords: Liver X receptor (LXR), Engelhardia roxburghiana, CYP7A1, ABCA1, SREBP1c, HepG2 cells

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Authors: Milijana N. Miljkovic, Viktorija M. Dragojevic-Simic, Nemanja K. Rancic, Vesna M. Jacevic, Snezana B. Djordjevic, Momir M. Mikov, Aleksandra M. Kovacevic

Abstract:

Itraconazole (ITZ) is a weak base and extremely lipophilic compound, with water solubility as a rate-limiting step in its absorption from the gastrointestinal tract. Its absolute bioavailability, about 55%, is maximal when its oral formulation, capsules, are taken immediately after a full meal. Peak plasma concentrations (Cmax) are reached within 2 to 5 hrs after their administration. ITZ undergoes extensive hepatic metabolism by human CYP3A4 isoenzyme and more than 30 different metabolites have been identified. One of the main ones is hydroxyitraconazole (HITZ), in which plasma concentrations are almost twice higher than those of ITZ. Gender differences in drug PK (Pharmacokinetics) have already been recognized, but variations in metabolism are believed to be their major cause. The aim of the study was to investigate the influence of gender on ITZ PK parameters after administration of oral capsule formulation, following 100 mg single dosing in healthy adult volunteers under fed conditions. The single-center, open-label PK study was performed. PK analyses included PK parameters obtained after a single 100 mg dose administration of itraconazole capsules to 48 females and 66 males. Blood samples were collected at pre-dose and up to 72.0 h after administration (1.0, 2.0, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0, 9.0, 12.0, 24.0, 36.0 and 72.0 hrs). The calculated pharmacokinetic parameters, based on the plasma concentrations of itraconazole and hydroxyitraconazole, were Cmax, AUClast, and AUCtot. Plasma concentrations of ITZ and HITZ were determined using a validated liquid chromatographic method with mass spectrometric detection, while pharmacokinetic parameters were estimated using non-compartmental methods. The pharmacokinetic analyses were performed using Kinetica software version 5.0. The mean value of ITZ Cmaxmen was 74.79 ng/ml, and Cmaxwomen was 51.291 ng/ml (independent samples test; p = 0.005). Hydroxyitraconazole had a mean value of Cmaxmen 106.37 ng/ml, and the mean value Cmaxwomen was 70.05 ng/ml. Women had, on average, lower AUClast and Cmax than men. AUClastmen for ITZ was 736.02 ng/mL*h and AUClastwomen was 566.62 ng/mL*h, while AUClastmen for HITZ was 1154.80 was ng/mL*h and AUClastwomen for HITZ was 708.12 ng/mL*h (independent samples test; p = 0.033). The mean values of ITZ AUCtotmen were 884.73 ng/mL*h and AUCtotwomen was 685.10 ng/mL*h. AUCtotmen for HITZ was 1290.41 ng/mL*h, while AUCtotwomen for HIZT was 788.60 ng/mL*h (p < 0.001). The results could point out to lower oral bioavailability of ITZ in women, since values of Cmax, AUClast, and AUCtot of both ITZ and HITZ were significantly lower in women than in men, respectively. The reason may be higher expression and activity of CYP3A4 in women than in men, but there also may be differences in other PK parameters. High variability of both ITZ and HITZ concentrations in both genders confirmed that ITZ is a highly variable drug. Further examinations of its PK are needed to justify strategies for therapeutic drug monitoring in patients treated by this antifungal agent.

Keywords: itraconazole, gender, hydroxyitraconazole, pharmacokinetics

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