Search results for: drug affordability

Authors: John Hang Leung, Shyh-Yau Wang, Hei-Tung Yip, Fion, Ho Tsung-chin, Agnes LF Chan

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Objectives: Platinum-resistant ovarian cancer has a short overall survival of 9–12 months and limited treatment options. The combination of immunotherapy and targeted therapy appears to be a promising treatment option for patients with ovarian cancer, particularly to patients with platinum-resistant recurrent ovarian cancer (PRrOC). However, there are no direct head-to-head clinical trials comparing their efficacy and toxicity. We, therefore, used a network to directly and indirectly compare seven newer immunotherapies or targeted therapies combined with chemotherapy in platinum-resistant relapsed ovarian cancer, including antibody-drug conjugates, PD-1 (Programmed death-1) and PD-L1 (Programmed death-ligand 1), PARP (Poly ADP-ribose polymerase) inhibitors, TKIs (Tyrosine kinase inhibitors), and antiangiogenic agents. Methods: We searched PubMed (Public/Publisher MEDLINE), EMBASE (Excerpta Medica Database), and the Cochrane Library electronic databases for phase II and III trials involving PRrOC patients treated with immunotherapy or targeted therapy plus chemotherapy. The quality of included trials was assessed using the GRADE method. The primary outcomes compared were progression-free survival, the secondary outcomes were overall survival and safety. Results: Seven randomized controlled trials involving a total of 2058 PRrOC patients were included in this analysis. Bevacizumab plus chemotherapy showed statistically significant differences in PFS (Progression-free survival) but not OS (Overall survival) for all interested targets and immunotherapy regimens; however, according to the heatmap analysis, bevacizumab plus chemotherapy had a statistically significant risk of ≥grade 3 SAEs (Severe adverse effects), particularly hematological severe adverse events (neutropenia, anemia, leukopenia, and thrombocytopenia). Conclusions: Bevacizumab plus chemotherapy resulted in better PFS as compared with all interested regimens for the treatment of PRrOC. However, statistical differences in SAEs as bevacizumab plus chemotherapy is associated with a greater risk for hematological SAE.

Keywords: platinum-resistant recurrent ovarian cancer, network meta-analysis, immune checkpoint inhibitors, target therapy, antiangiogenic agents

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Authors: Apoorva D. R.

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INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a severe, potentially fatal syndrome in which there is excessive immune activation. The disease is seen in children and people of all ages, but infants from birth to 18 months are most frequently affected. HLH is a sporadic or familial condition that can be triggered by various events that disturb immunological homeostasis. In cases with a genetic predisposition and sporadic occurrences, infection is a frequent trigger. Because of the rarity of this disease, the diverse clinical presentation, and the lack of specificity in the clinical and laboratory results, prompt treatment is essential, but the biggest obstacle to a favorable outcome is frequently a delay in identification. CASE REPORT: Here we report a case of a 6-month-old male infant who presented to the dermatology outpatient with disseminated skin lesions present over the face, abdomen, scalp, and bilateral upper and lower limbs for the past month. The lesions were insidious in onset, initially started over the abdomen, and gradually progressed to involve other body parts. The patient also had a history of fever which was moderate in grade, on and off in nature for 1 month. There were no significant complaints in the past, family, or drug history. There was no history of feeding difficulties in the baby. Parents gave a history of developmental milestones appropriate for age. Examination findings include multiple well-defined monomorphic erythematous papules with a central crater present over bilateral cheeks. Few lichenoid shiny papules present over bilateral arms, legs, and abdomen. Ultrasound of the abdomen and pelvis showed mild degree hepatosplenomegaly, intraabdominal lymphadenopathy, and bilateral inguinal lymphadenopathy. Routine blood investigations showed anemia and lymphopenia. Multiple X-rays of the skull, chest, and bilateral upper and lower limbs were done and were normal. Histopathology features were suggestive of non-Langerhans cell cutaneous histiocytosis. CONCLUSION: HLH is a fatal and rare disease. A high level of suspicion and an interdisciplinary approach among experienced clinicians, pathologists, and microbiologists to define the diagnosis and causative disease are key to diagnosing this case. Early detection and treatment can reduce patient morbidity and mortality.

Keywords: histiocytosis, non langerhans cell, case report, fatal, rare

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Authors: S. Somerset, D. J. Hoare

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Participation in sport is linked to better mental and physical health in children and adults. Studies have shown children who participate in sports benefit from improved social skills, self-confidence, communication skills and a better quality of life. Children who participate in sports from a young age are also more likely to continue to have active lifestyles during adulthood. This is an important consideration with a nation where physical activity levels are declining and the incidences of obesity are rising. Getting children active and keeping them active can provide long term health benefits to the individual but also a potential reduction in health costs in the future. This systematic review aims to identify the barriers to participation in sport for children aged up to 18 years and encompasses both qualitative and quantitative studies. The bibliographic databases, EMBASE, Medline, CINAHL and SportDiscus were searched. Additional hand searches were carried out on review articles found in the searches to identify any studies that may have been missed. Studies involving children up to 18 years without additional needs focusing on barriers to participation in sport were included. Randomised control trials, policy guidelines, studies with sport as an intervention, studies focusing on the female athlete triad, tobacco abuse, alcohol abuse, drug abuse, pre exercise testing, and cardiovascular disease were excluded. Abstract review, full paper review and quality appraisal were conducted by two researchers. A consensus meeting took place to resolve any differences at the abstract, full text and data extraction / quality appraisal stages. The CASP qualitative studies appraisal tool and the CASP cohort studies tool (excluding question 3 and 4 which refer to interventions) were used for quality appraisal in this review. The review identified several salient barriers to participation in sport for children. These barriers ranged from the uniform worn during school physical education lessons to the weather during participation in sport. The most commonly identified barriers in the review include parental support, time allocation, location of the activity and the cost of the activity. Therefore, it would be beneficial for a greater provision to be made within the school environment for children to participate sport. This can reduce the cost and time commitment required from parents to encourage participation. This would help to increase activity levels of children, which ultimately can only be a good thing.

Keywords: barrier, children, participation, sport

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Authors: A. Y. Tsidulko, T. M. Pankova, E. V. Grigorieva

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High-grade gliomas are the most frequent and most aggressive brain tumors which are characterized by active invasion of tumor cells into the surrounding brain tissue, where the extracellular matrix (ECM) plays a crucial role. Disruption of ECM can be involved in anticancer drugs effectiveness, side-effects and also in tumor relapses. The anti-inflammatory agent dexamethasone is a common drug used during high-grade glioma treatment for alleviating cerebral edema. Although dexamethasone is widely used in the clinic, its effects on normal brain tissue ECM remain poorly investigated. It is known that proteoglycans (PGs) are a major component of the extracellular matrix in the central nervous system. In our work, we studied the effects of dexamethasone on the ECM proteoglycans (syndecan-1, glypican-1, perlecan, versican, brevican, NG2, decorin, biglican, lumican) using RT-PCR in the experimental animal model. It was shown that proteoglycans in rat brain have age-specific expression patterns. In early post-natal rat brain (8 days old rat pups) overall PGs expression was quite high and mainly expressed PGs were biglycan, decorin, and syndecan-1. The overall transcriptional activity of PGs in adult rat brain is 1.5-fold decreased compared to post-natal brain. The expression pattern was changed as well with biglycan, decorin, syndecan-1, glypican-1 and brevican becoming almost equally expressed. PGs expression patterns create a specific tissue microenvironment that differs in developing and adult brain. Dexamethasone regimen close to the one used in the clinic during high-grade glioma treatment significantly affects proteoglycans expression. It was shown that overall PGs transcription activity is 1.5-2-folds increased after dexamethasone treatment. The most up-regulated PGs were biglycan, decorin, and lumican. The PGs expression pattern in adult brain changed after treatment becoming quite close to the expression pattern in developing brain. It is known that microenvironment in developing tissues promotes cells proliferation while in adult tissues proliferation is usually suppressed. The changes occurring in the adult brain after dexamethasone treatment may lead to re-activation of cell proliferation due to signals from changed microenvironment. Taken together obtained data show that dexamethasone treatment significantly affects the normal brain ECM, creating the appropriate microenvironment for tumor cells proliferation and thus can reduce the effectiveness of anticancer treatment and promote tumor relapses. This work has been supported by a Russian Science Foundation (RSF Grant 16-15-10243)

Keywords: dexamthasone, extracellular matrix, glioma, proteoglycan

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Authors: Oluwafunmibi Omotayo Fasanya, Augustine Kena Adjei

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Diabetic nephropathy (DN) is a major complication of diabetes, with fibrosis and propionate metabolism playing critical roles in its progression. Identifying biomarkers linked to these pathways may provide novel insights into DN diagnosis and treatment. This study aims to identify biomarkers associated with fibrosis and propionate metabolism in DN. Analyze the biological pathways and regulatory mechanisms of these biomarkers. Develop a machine learning model to predict DN-related biomarkers and validate their functional roles. Publicly available transcriptome datasets related to DN (GSE96804 and GSE104948) were obtained from the GEO database (https://www.ncbi.nlm.nih.gov/gds), and 924 propionate metabolism-related genes (PMRGs) and 656 fibrosis-related genes (FRGs) were identified. The analysis began with the extraction of DN-differentially expressed genes (DN-DEGs) and propionate metabolism-related DEGs (PM-DEGs), followed by the intersection of these with fibrosis-related genes to identify key intersected genes. Instead of relying on traditional models, we employed a combination of deep neural networks (DNNs) and ensemble methods such as Gradient Boosting Machines (GBM) and XGBoost to enhance feature selection and biomarker discovery. Recursive feature elimination (RFE) was coupled with these advanced algorithms to refine the selection of the most critical biomarkers. Functional validation was conducted using convolutional neural networks (CNN) for gene set enrichment and immunoinfiltration analysis, revealing seven significant biomarkers—SLC37A4, ACOX2, GPD1, ACE2, SLC9A3, AGT, and PLG. These biomarkers are involved in critical biological processes such as fatty acid metabolism and glomerular development, providing a mechanistic link to DN progression. Furthermore, a TF–miRNA–mRNA regulatory network was constructed using natural language processing models to identify 8 transcription factors and 60 miRNAs that regulate these biomarkers, while a drug–gene interaction network revealed potential therapeutic targets such as UROKINASE–PLG and ATENOLOL–AGT. This integrative approach, leveraging deep learning and ensemble models, not only enhances the accuracy of biomarker discovery but also offers new perspectives on DN diagnosis and treatment, specifically targeting fibrosis and propionate metabolism pathways.

Keywords: diabetic nephropathy, deep neural networks, gradient boosting machines (GBM), XGBoost

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Authors: Zeynep Yazgan, Gökhan Aygün, Reyhan Çalışkan

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Objective: Invasive fungal infections are a serious threat in terms of morbidity and mortality, especially in immunocompromised patients. The most frequently isolated agents are Aspergillus genus fungi, and sensitivity to azoles, which are the first choice in treatment, decreases. In our study, we aimed to investigate the use of the agar plate screening method as a fast, easy, and practical method in determining azole resistance in Aspergillus spp. species. Methods: Our study was conducted with 125 Aspergillus spp. isolates produced from various clinical samples. Aspergillus spp. isolates were identified by conventional methods and azole resistance was determined by gradient test and agar plate screening method. Broth microdilution method was applied to resistant isolates, and CypA-L98H and CypA-M220 mutations in the cyp51A gene were investigated. Results: In our study, 55 A. fumigatus complex (44%), 42 A. flavus (33.6%), 6 A. terreus (5%), 4 A. niger (3%) and 18 Aspergillus spp. (14%) were identified. With the gradient test method, resistance to VOR and POS was detected in 1 (1.8%) of A.fumigatus isolates, and resistance to ITR was detected in 3 (5.45%). With the agar plate method, 1 of the A.fumigatus isolates (1.8%) had VOR, ITR, POS, 1 of the A.terreus isolates (16.7%) had VOR, 1 of the A.niger isolates (25%) had ITR. Resistance to VOR and POS was detected in 2 Aspergillus spp. isolates (11%), and resistance to ITR was detected in 1 (5.6%). Sensitivity and specificity were determined as 100% for VOR and POS in A. fumigatus species, 33.3% and 100% for ITR, respectively, 100% for ITR in A. flavus species, and 100% for ITR and POS in A. terreus species. By broth microdilution method in 7 isolates in which resistance was detected by gradient test and/or agar plate screening method; 1 A.fumigatus resistant to ITR, VOR, POS, 2 A.fumigatus resistant to ITR, 2 Aspergillus spp. ITR, VOR, POS MICs were determined as 2µg/ml and 8µg/ml, 8µg/ml and >32µg/ml, 0.5µg/ml and 4µg/ml, respectively. CypA-L98H mutations were detected in 5 of these isolates, CypA-M220 mutations were detected in 6, and no mutation was detected in 1. CypA-L98H and CypA-M220 mutations were detected in 1 isolate for which resistance was not detected. Conclusion: The need for rapid antifungal susceptibility screening tests is increasing in the treatment of aspergillosis. Although the sensitivity of the agar plate method was determined to be 33.3% for A.fumigatus ITR in our study, its sensitivity and specificity were determined to be 100% for ITR, VOR, and POS in other species. The low sensitivity value detected for A.fumigatus showed that agar plate drug concentrations should be updated in accordance with the latest regulations of EUCAST guidelines. The CypA-L98H and CypA-M220 mutations detected in our study suggested that the distribution of azole resistance-related mutations in different regions in our country should be investigated. In conclusion, it is thought that the agar plate method, which can be easily applied to detect azole resistance, is a fast and practical method in routine use and can contribute to both the determination of effective treatment strategies and the generation of epidemiological data.

Keywords: Aspergillus, agar plate, azole resistance, cyp51A, cypA-L98H, cypA-M220

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Authors: Bo Keun Lee, Doo Yeon Kwon, Ji Hoon Park, Gun Hee Lee, Ji Hye Baek, Heung Jae Chun, Young Joo Koh, Moon Suk Kim

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Thermo-responsive materials are viscoelastic materials that undergo a sol-to-gel phase transition at a specific temperature and many materials have been developed. MPEG-b-PCL (MPC) as a thermo-responsive material contained hydrophilic and hydrophobic segments and it formed an ordered crystalline structure of hydrophobic PCL segments in aqueous solutions. The ordered crystalline structure packed tightly or aggregated and finally induced an aggregated gel through intra- and inter-molecular interactions as a function of temperature. Thus, we introduced anionic and cationic groups into the end positions of the PCL chain to alter the hydrophobicity of the PCL segment. Introducing anionic and cationic groups into the PCL end position altered their solubility by changing the crystallinity and hydrophobicity of the PCL block domains. These results indicated that the properties of the end group in the hydrophobic PCL blockand the balance between hydrophobicity and hydrophilicity affect thermo-responsivebehavior of the copolymers in aqueous solutions. Thus, we concluded that determinant of the temperature-dependent thermo-responsive behavior of MPC depend on the ionic end group in the PCL block. So, we introduced zwitterionic end groups to investigate the thermo-responsive behavior of MPC. Methoxypoly(ethylene oxide) and ε-caprolactone (CL) were randomly copolymerized that introduced varying hydrophobic PCL lengths and an MPC featuring a zwitterionic sulfobetaine (MPC-ZW) at the chain end of the PCL segment. The MPC and MPC-ZW copolymers were obtained formed sol-state at room temperature when prepared as 20-wt% aqueous solutions. The solubility of MPC decreased when the PCL block was increased from molecular weight. The solubilization time of MPC-2.4k was around 20 min and MPC-2.8k, MPC-3.0k increased to 30 min and 1 h, respectively. MPC-3.6k was not solubilized. In case of MPC-ZW 3.6k, However, the zwitterion-modified MPC copolymers were solubilized in 3–5 min. This result indicates that the zwitterionic end group of the MPC-ZW diblock copolymer increased the aqueous solubility of the diblock copolymer even when the length of the hydrophobic PCL segment was increased. MPC and MPC-ZW diblock copolymers that featuring zwitterionic end groups were synthesized successfully. The sol-to-gel phase-transition was formed that specific temperature depend on the length of the PCL hydrophobic segments introduced and on the zwitterion groups attached to the MPC chain end. This result indicated that the zwitterionic end groups reduced the hydrophobicity in the PCL block and changed the solubilization. The MPC-ZW diblock copolymer can be utilized as a potential injectable drug and cell carrier.

Keywords: thermo-responsive material, zwitterionic, hydrophobic, crystallization, phase transition

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Authors: Eitedal Daoud, Reda M.Daoud, Khaled Abdel-Wahhab, Maha M.Saber, Lobna Saber

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Background: Cis-platin is a widely used chemotherapeutic drug to treat many malignant disorders including head and neck malignancies. Oto-nephrotxicity is an important and dose - limiting side effect of cis - platin therapy. Nowadays, more attention had been paid to oto-toxicity caused with cis-platin. Aim of the Work: This study was designed to investigate the potential protective effect of Whey protein (WP) against cis-platin induced ototoxicity compared to the effect of N-acetylcysteine (NAC) in rats. Methodology: Male albino rats were randomly divided into 6 groups: untreated rats (control), rats orally treated with whey protein (1g/kg b.w/day) for seven executive days, rats treated orally with N-acetylcysteine (500 mg/kgb.w /day) for seven executive days, rates intoxicated intraperitoneal (ip) with cis- platin (10 mg/kgb.w. once), rats treated with whey protein (1g/kgb.w./day) for seven executive days) followed by one injection (ip) of cis-platin(10 mg/kg b.w.) one hour after the last oral administration of whey protein, rats treated with N- acetylcysteine (for seven executive days followed by one injection (ip) of cis-platin (10 mg/kgb.w) one hour after the last oral administration of N-acetylcysteine. The organ of Corti, the stria vascularis and spiral ganglia were visualized by light microscopy at different magnifications. Results: Cis-platin intoxicated animals showed a significant decrease in serum level of total antioxidant capacity (TAC),with inhibition in the activity of serum glutathione-s transferase(GST) and paraoxonnase-1 (PON-1) in comparison with control. Group treated with either NAC or WP with cis-platin showed significant elevation in the activity of both GST & PON-1 with increased serum level of TAC when compared with cis-platin intoxicated rats. Animals treated with NAC or WP with cis-platin compared to those treated with cis-platin alone showed marked degree of improvement towards control rats as there was significant drop in the serum level of cortecosterone, nitric oxide (NO), and melandialdehyde (MDA).Histopathologic, in NAC pretreated group there was no changes in stria vascularis or spiral ganglia. In group pretreated with WP, there was no histopathologic alteration detected in the organ of Corti and Reissers membrane but oedema and haemorrhage were founded in the stria vascularis in small focal manner. Conclusion: Our finding showed that Whey protein is a natural dietary supplement product proved its ability of protection of anti-oxidant system and the cochlea against cis-platin induced ototoxicity.

Keywords: anti-oxidant, cis-platin, N-acetylcysteine, ototoxicity, whey protein

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Authors: Vasudha Govil, Prashant Kumar, Ishwar Singh, Kiranpreet Kaur

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Traumatic brain injury leads to elevated intracranial pressure. Intraocular pressure (IOP) may also be affected by intracranial pressure. Increased venous pressure in the cavernous sinus is transmitted to the episcleral veins, resulting in an increase in IOP. All drugs used in anesthesia induction can change IOP. Irritation of the gag reflex after usage of the endotracheal tube can also increase IOP; therefore, the administration of anesthetic drugs, which make the lowest change in IOP, is important, while cardiovascular depression must also be avoided. Thiopentone decreases IOP by 40%, whereas etomidate decreases IOP by 30-60% for up to 5 minutes. Hundred patients (age 18-55 years) who underwent emergency craniotomy for TBI are selected for the study. Patients are randomly assigned to two groups of 50 patients each accord¬ing to the drugs used for induction: group T was given thiopentone sodium (5mg kg-1) and group E was given etomi¬date (0.3mg kg-1). Preanaesthesia intraocular pressure (IOP) was measured using Schiotz tonometer. Induction of anesthesia was achieved with etomidate (0.3mg kg-1) or thiopentone (5mg kg-1) along with fentanyl (2 mcg kg-1). Intravenous rocuronium (0.9mg kg-1) was given to facilitate intubation. Intraocular pressure was measured after 1 minute of induction agent administration and 5 minutes after intubation. Maintainance of anesthesia was done with isoflurane in 50% nitrous oxide with fresh gas flow of 5 litres. At the end of the surgery, the residual neuromuscular block was reversed and the patient was shifted to ward/ICU. Patients in both groups were comparable in terms of demographic profile. There was no significant difference between the groups for the hemody¬namic and respiratory variables prior to thiopentone or etomidate administration. Intraocular pressure in thiopentone group in left eye and right eye before induction was 14.97±3.94 mmHg and 14.72±3.75 mmHg respectively and for etomidate group was 15.28±3.69 mmHg and 15.54±4.46 mmHg respectively. After induction IOP decreased significantly in both the eyes (p<0.001) in both the groups. After 5 min of intubation IOP was significantly less than the baseline in both the eyes but it was more than the IOP after induction with the drug. It was found that there was no statistically significant difference in IOP between the two groups at any point of time. Both the drugs caused a significant decrease in IOP after induction and after 5 minutes of endotracheal intubation. The mechanism of decrease in IOP by intravenous induction agents is debatable. Systemic hypotension after the induction of anaesthesia has been shown to cause a decrease in intra-ocular pressure. A decrease in the tone of the extra-ocular muscles can also result in a decrease in intra-ocular pressure. We observed that it is appropriate to use etomidate as an induction agent when elevation of intra-ocular pressure is undesirable owing to the cardiovascular stability it confers in the patients.

Keywords: etomidate, intraocular pressure, thiopentone, traumatic

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Authors: Wiesława Klimek-Piotrowska, Mateusz K. Hołda, Mateusz Koziej, Katarzyna Piątek, Jakub Hołda

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Introduction: The coronary sinus venous system (CSVS), which has always been overshadowed by the coronary arterial tree, has recently begun to attract more attention. Since it is a target for clinicians the knowledge of its anatomy is essential. Cardiac resynchronization therapy, catheter ablation of cardiac arrhythmias, defibrillation, perfusion therapy, mitral valve annuloplasty, targeted drug delivery, and retrograde cardioplegia administration are commonly used therapeutic methods involving the CSVS. The great variability in the course of coronary veins and tributaries makes the diagnostic and therapeutic processes difficult. Our aim was to investigate detailed anatomy of most common clinically used CSVS`s structures: the coronary sinus with its ostium, great cardiac vein, posterior vein of the left ventricle, middle cardiac vein and oblique vein of the left atrium. Methodology: This is a prospective study of 70 randomly selected autopsied hearts dissected from adult humans (Caucasian) aged 50.1±17.6 years old (24.3% females) with BMI=27.6±6.7 kg/m2. The morphology of the CSVS was assessed as well as its precise measurements were performed. Results: The coronary sinus (CS) with its ostium was present in all hearts. The mean CS ostium diameter was 9.9±2.5mm. Considered ostium was covered by its valve in 87.1% with mean valve height amounted 5.1±3.1mm. The mean percentage coverage of the CS ostium by the valve was 56%. The Vieussens valve was present in 71.4% and was unicuspid in 70%, bicuspid in 26% and tricuspid in 4% of hearts. The great cardiac vein was present in all cases. The oblique vein of the left atrium was observed in 84.3% of hearts with mean length amounted 20.2±9.3mm and mean ostium diameter 1.4±0.9mm. The average length of the CS (from the CS ostium to the Vieussens valve) was 31.1±9.5mm or (from the CS ostium to the ostium of the oblique vein of the left atrium) 28.9±10.1mm and both were correlated with the heart weight (r=0.47; p=0.00 and r=0.38; p=0.006 respectively). In 90.5% the ostium of the oblique vein of the left atrium was located proximally to the Vieussens valve, in remaining cases was distally. The middle cardiac vein was present in all hearts and its valve was noticed in more than half of all the cases (52.9%). The posterior vein of the left ventricle was observed in 91.4% of cases. Conclusions: The CSVS is vastly variable and none of basic hearts parameters is a good predictor of its morphology. The Vieussens valve could be a significant obstacle during CS cannulation. Caution should be exercised in this area to avoid coronary sinus perforation. Because of the higher incidence of the presence of the oblique vein of the left atrium than the Vieussens valve, the vein orifice is more useful in determining the CS length.

Keywords: cardiac resynchronization therapy, coronary sinus, Thebesian valve, Vieussens valve

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Authors: M. M. Essa, S. Subash, M. Akbar, S. Al-Adawi, A. Al-Asmi, G. J. Guillemein

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Transgenic (tg) mice which contain an amyloid precursor protein (APP) gene mutation, develop extracellular amyloid beta (Aβ) deposition in the brain, and severe memory and behavioral deficits with age. These mice serve as an important animal model for testing the efficacy of novel drug candidates for the treatment and management of symptoms of Alzheimer's disease (AD). Several reports have suggested that oxidative stress is the underlying cause of Aβ neurotoxicity in AD. Date palm fruits contain very high levels of antioxidants and several medicinal properties that may be useful for improving the quality of life in AD patients. In this study, we investigated the effect of dietary supplementation of Omani date palm fruits on the memory, anxiety and learning skills along with inflammation in an AD mouse model containing the double Swedish APP mutation (APPsw/Tg2576). The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 2% and 4% Date palm fruits. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4-5 months and 18-19 months using the Morris water maze test, rota rod test, elevated plus maze test, and open field test. Further, inflammatory parameters also analyzed. APPsw/Tg2576 mice that were fed a standard chow diet without dates showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination along with increased inflammation compared to the wild type mice on the same diet, at the age of 18-19 months In contrast, PPsw/Tg2576 mice that were fed a diet containing 2% and 4% dates showed a significant improvements in memory, learning, locomotor function, and anxiety with reduced inflammatory markers compared to APPsw/Tg2576 mice fed the standard chow diet. Our results suggest that dietary supplementation with dates may slow the progression of cognitive and behavioral impairments in AD. The exact mechanism is still unclear and further extensive research needed.

Keywords: Alzheimer's disease, date palm fruits, Oman, cognitive decline, memory loss, anxiety, inflammation

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Authors: Sanjay Singh, Parameswara Rao Vuddanda

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The aim of the present study is study the factual benefit of nano size and surface coating of p-gp efflux inhibitor on enhancement of bioavailability of Berberine chloride (BBR); a p-gp substrate. In addition, 28 days sub acute oral toxicity study was also conducted to assess the toxicity of the formulation on chronic administration. BBR loaded polymeric nanoparticles (BBR-NP) were prepared by nanoprecipitation method. BBR NP were surface coated (BBR-SCNP) with the 1 % w/v of vitamin E TPGS. For bioavailability study, total five groups (n=6) of rat were treated as follows first; pure BBR, second; physical mixture of BBR, carrier and vitamin E TPGS, third; BBR-NP, fourth; BBR-SCNP and fifth; BBR and verapamil (widely used p-gp inhibitor). Blood was withdrawn at pre-set timing points in 24 hrs study and drug was quantified by HPLC method. In oral chronic toxicity study, total four groups (n=6) were treated as follows first (control); water, second; pure BBR, third; BBR surface coated nanoparticles and fourth; placebo BBR surface coated nanoparticles. Biochemical levels of liver (AST, ALP and ALT) and kidney (serum urea and creatinine) along with their histopathological studies were also examined (0-28 days). The AUC of BBR-SCNP was significantly 3.5 folds higher compared to all other groups. The AUC of BBR-NP was 3.23 and 1.52 folds higher compared to BBR solution and BBR with verapamil group, respectively. The physical mixture treated group showed slightly higher AUC than BBR solution treated group but significantly low compared to other groups. It indicates that encapsulation of BBR in nanosize form can circumvent P-gp efflux effect. BBR-NP showed pharmacokinetic parameters (Cmax and AUC) which are near to BBR-SCNP. However, the difference in values of T1/2 and clearance indicate that surface coating with vitamin E TPGS not only avoids the P-gp efflux at its absorption site (intestine) but also at organs which are responsible for metabolism and excretion (kidney and liver). It may be the reason for observed decrease in clearance of BBR-SCNP. No toxicity signs were observed either in biochemical or histopathological examination of liver and kidney during toxicity studies. The results indicate that administration of BBR in surface coated nanoformulation would be beneficial for enhancement of its bioavailability and longer retention in systemic circulation. Further, sub acute oral dose toxicity studies for 28 days such as evaluation of intestine, liver and kidney histopathology and biochemical estimations indicated that BBR-SCNP developed were safe for long use.

Keywords: bioavailability, berberine nanoparticles, p-gp efflux inhibitor, nanoprecipitation method

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Authors: A. H. Taghdisi, M. Mirmohammadi, S. Kamali

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Evening primrose (Oenothera biennis L.) is a biennial and herbaceous and one of the most important species of medicinal plants in the world. due to the production of unsaturated fatty acids such as linoleic acid, alpha-linolenic acid, etc. in its seeds and roots, and compounds such as kaempferol in its leaves, Evening primrose has important medicinal efficiency such as reducing premenstrual problems, acceleration of wound healing, inhibiting platelet aggregation, sedation of cardiovascular diseases, and treatment of viral infections. The sap of the plant is used to treat warts, and the plant itself is used as a charm against mental and spiritual diseases and poisonous animals. Its leaves have significant antibacterial activity against yellow staphylococci. It is also used in the treatment of poisoning, especially the toxication caused by the consumption of alcoholic beverages, in the treatment of arteriosclerosis and diseases caused by liver cell insufficiency. Low germination and production speed are the problems of evening primrose growth and propagation. In the present study, extracts were obtained from four components (flowers, stems, seeds, leaves) of the evening primrose plant using the Soxhlet apparatus. To measure the antibacterial properties against MDR bacteria, microbial methods, including dilution, cultivation on a plate containing nutrient agar culture medium, and disc diffusion in agar, were performed using Staphylococcus aureus and Escherichia coli bacteria on all four extracts. The maximum antibacterial activity related to the dilution method was obtained in all extracts. In the plate culture method, antibacterial activity was obtained for all extracts in the nutrient agar medium. The maximum diameter of the non-growth halo was obtained in the disc diffusion method in agar in the leaf extract. The statistical analysis of the microbial part was done by one-way ANOVA test (SPSS). By comparing the amount of omega-3 in extracts of Iranian and foreign oils available in the market and the extracts extracted from evening primrose plant samples with gas chromatography, it is shown that the stem extract had the most omega-3 (oleic acid) and compared to the extract of the mentioned oils, it had the highest amount of omega-3 overall. Also, the amount of omega-3 in the extract of Iranian oils was much higher than in the extract of foreign oils. It should be noted that the extract of foreign oils had a more complete composition of omega-3 than the extract of Iranian oils.

Keywords: antibacterial activity, MDR bacteria, evening primrose, omega-3

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Authors: Maneesha Pahlani, Najmin Sultana

Abstract:

A hospital is one of the most suitable places for acquiring an infection because it harbors a high population of virulent strains of microorganisms that may be resistant to antibiotics, especially the prevalence of Methicillin-Resistant Staphylococcus Aureus (MRSA) infections. The hospital-acquired infection has become a global challenge. In developed countries, healthcare-associated infections occur in 5-15% of hospitalized clients, affecting 9-37% of those admitted to intensive care units (ICU). A non-experimental descriptive study was conducted among 50 nursing officers working in a selected hospital in Bangalore to assess the nursing officers’ level of knowledge regarding the prevention and management of MRSA infections and to associate the pre-test knowledge mean scores of nursing officers with selected socio-demographic variables. Data was collected using a structured questionnaire consisting of socio-demographic data and a structured questionnaire on knowledge regarding the prevention and management of MRSA infections. The data was analyzed in terms of frequencies and percentages for the analysis of demographic variables and computing chi-square to determine the association between knowledge means scores and selected demographic variables. The study findings revealed that the nursing officer had an overall good level of knowledge (63.05%) regarding the prevention and management of MRSA infections, and there is no significant association found between the level of knowledge mean scores for prevention and management of MRSA infection with the selected socio-demographic variables. However, the categorization of knowledge items showed that the nursing officer must thoroughly receive education on correct guidance and information regarding MRSA infection control policy, including measures and practices on hygiene precautions and information regarding antibiotic resistance for effective nursing care to patients with MRSA infections. The conclusions drawn from the study findings showed that it is necessary that the nursing officer thoroughly receive education on correct guidance and information regarding MRSA infection control policy, including measures and practices on hygiene precautions and information regarding antibiotic resistance to provide effective nursing care to patients with MRSA infection as they constantly care for the patient who can be at risk for multi-drug resistance organisms to reduce the risk of MRSA infection in hospital care settings as well community settings.

Keywords: MRSA, nursing officers, knowledge, preventive and management

Procedia PDF Downloads 67

Authors: Ana Carolina Kogawa, Selma Gutierrez Antonio, Hérida Regina Nunes Salgado

Abstract:

Rifaximin is an oral antimicrobial, gut - selective and not systemic with adverse effects compared to placebo. It is used for the treatment of hepatic encephalopathy, travelers diarrhea, irritable bowel syndrome, Clostridium difficile, ulcerative colitis and acute diarrhea. The crystalline form present in the rifaximin with minimal systemic absorption is α, being the amorphous form significantly different. Regulators are increasingly attention to polymorphisms. Polymorphs can change the form by altering the drug characteristics compromising the effectiveness and safety of the finished product. International Conference on Harmonization issued the ICH Guidance Q6A, which aim to improve the control of polymorphism in new and existing pharmaceuticals. The objective of this study was to obtain polymorphic forms of rifaximin employing recrystallization processes and characterize them by thermal analysis (thermogravimetry - TG and differential scanning calorimetry - DSC), X-ray diffraction, scanning electron microscopy and solubility test. Six polymorphic forms of rifaximin, designated I to VI were obtained by the crystallization process by evaporation of the solvent. The profiles of the TG curves obtained from polymorphic forms of rifaximin are similar to rifaximin and each other, however, the DTG are different, indicating different thermal behaviors. Melting temperature values of all the polymorphic forms were greater to that shown by the rifaximin, indicating the higher thermal stability of the obtained forms. The comparison of the diffractograms of the polymorphic forms of rifaximin with rifaximin α, β and γ constant in patent indicate that forms III, V and VI are formed by mixing polymorph β and α and form III is formed by polymorph β. The polymorphic form I is formed by polymorph β, but with a significant amount of amorphous material. Already, the polymorphic form II consists of polymorph γ, amorphous. In scanning electron microscope is possible to observe the heterogeneity of morphological characteristics of crystals of polymorphic forms among themselves and with rifaximin. The solubility of forms I and II was greater than the solubility of rifaximin, already, forms III, IV and V presented lower solubility than of rifaximin. Similarly, the bioavailability of the amorphous form of rifaximin is considered significantly higher than the form α, the polymorphic forms obtained in this work can not guarantee the excellent tolerability of the reference medicine. Therefore, studies like these are extremely important and they point to the need for greater requirements by the regulatory agencies competent about polymorphs analysis of the raw materials used in the manufacture of medicines marketed globally. These analyzes are not required in the majority of official compendia. Partnerships between industries, research centers and universities would be a viable way to consolidate researches in this area and contribute to improving the quality of solid drugs.

Keywords: electronic microscopy, polymorphism, rifaximin, solubility, X-ray diffraction

Procedia PDF Downloads 662

Authors: Hayley Lawrence, Nabi Shah, Sarah Dyer

Abstract:

Aims: Lumbar punctures are a common bedside procedure performed in acute medicine. Published guidance exists on the standardised documentation of invasive procedures in order to reduce the risk of complications. The audit aim was to assess current standards of documentation in accordance with both the GMC and the National Standards for Invasive Procedures guidelines. A second cycle was conducted after introducing a standardised sticker created using current guidelines. This would assess whether the sticker improved documentation, aiming for 100% standard in each step of the procedure. Methods: An initial prospective audit of current practice was conducted over a 3-month period. Patients were identified by their presenting complaints and by colleagues assessing acute medical patients. Initial findings were presented locally, and a further prospective audit was conducted following the implementation of a standardised sticker. Results: 19 lumbar punctures were included in the first cycle and 13 procedures in the second. Pre-procedure documentation was collected for each cycle, whereby documentation of ‘Indication’ improved from 5.3% to 84.6%, ‘Consent’ from 84.2% to 100%, ‘Coagulopathy’ from 0% to 61.5%, ‘Drug Chart checked’ from 0% to 100%, ‘Position of patient’ from 26.3% to 100% and use of ‘Aseptic Technique’ from 83.3% to 100% from the first to the second cycle respectively. ‘Level of Doctor’ and ‘Supervision’ decreased from 53% to 31% and 53% to 46%, respectively, in the second cycle. Documentation of the procedure itself also demonstrated improvements, with ‘Level of Insertion’ 15.8% to 100%, ‘Name of Antiseptic Used’ 11.1% to 69.2%, ‘Local Anaesthetic Used’ 26.3% to 53.8%, ‘Needle Gauge’ 42.1% to 76.9%, ‘Number of Attempts’ 78.9% to 100% and ‘Traumatic/Atraumatic’ procedure 26.3% to 92.3%, respectively. A similar number of opening pressures were documented in each cycle at 57.9% and 53.8%, respectively, but its documentation was deemed ‘Not Applicable’ in a higher number of patients in the second cycle. Post-procedure documentation improved, with ‘Number of Samples obtained’ increasing from 52.6% to 92.3% and documentation of ‘Immediate Complications’ increasing from 78.9% to 100%. ‘Dressing Applied’ was poorly documented in the first cycle at 16.7%. This was not included on the standardised sticker, resulting in 0% documentation in the second cycle. Documentation of Clinicians’ Name and Bleep reduced from 63.2% to 15.4%, but when the name only was analysed, this increased to 84.6%. Conclusions: Standardised stickers for lumbar punctures do improve documentation and hence should result in improved patient safety. There is still room for improvement to reach 100% standard in each area, especially with respect to the clinician’s name and contact details being documented. Final adjustments will be made to the sticker before being included in a lumbar puncture kit, which will be made readily available in the acute medical wards. Future audits could be extended to include other common bedside procedures performed in acute medicine to ensure documentation of all these procedures reaches 100% standard.

Keywords: invasive procedure, lumbar puncture, medical record keeping, procedure checklist, procedure documentation, standardised documentation

Procedia PDF Downloads 101

Authors: Najmin Sultana, Maneesha Pahlani

Abstract:

A hospital is one of the most suitable places for acquiring an infection because it harbors a high population of virulent strains of microorganisms that may be resistant to antibiotics, especially the prevalence of Methicillin-Resistant Staphylococcus Aureus (MRSA) infections. The hospital-acquired infection has become a global challenge. In developed countries, healthcare-associated infections occur in 5-15% of hospitalized clients, affecting 9-37% of those admitted to intensive care units (ICU). A non-experimental descriptive study was conducted among 50 nursing officers working in a selected hospital in bengaluru to assess the nursing officers’ level of knowledge regarding the prevention and management of MRSA infections and to associate the pre-test knowledge mean scores of nursing officers with selected socio-demographic variables. Data was collected using a structured questionnaire consisting of socio-demographic data and a structured questionnaire on knowledge regarding the prevention and management of MRSA infections. The data was analyzed in terms of frequencies and percentages for the analysis of demographic variables and computing chi-square to determine the association between knowledge means scores and selected demographic variables. The study findings revealed that the nursing officer had an overall good level of knowledge (63.05%) regarding the prevention and management of MRSA infections, and there is no significant association found between the level of knowledge mean scores for prevention and management of MRSA infection with the selected socio-demographic variables. However, the categorization of knowledge items showed that the nursing officer must thoroughly receive education on correct guidance and information regarding MRSA infection control policy, including measures and practices on hygiene precautions and information regarding antibiotic resistance for effective nursing care to patients with MRSA infections. The conclusions drawn from the study findings showed that it is necessary that the nursing officer thoroughly receive education on correct guidance and information regarding MRSA infection control policy, including measures and practices on hygiene precautions and information regarding antibiotic resistance to provide effective nursing care to patients with MRSA infection as they constantly care for the patient who can be at risk for multi-drug resistance organisms to reduce the risk of MRSA infection in hospital care settings as well community settings.

Keywords: MRSA, knowledge, nursing officers', prevention and management

Procedia PDF Downloads 58

Authors: H. Pegram, R. Stevens, L. De Girolamo

Abstract:

Aligned electrospun nanofibres act as effective neuronal and glial cell scaffolds that can be layered to contain multiple sheets harboring different cell populations. This allows personalised biofunctional prostheses to be manufactured with both acellular and cellularised layers for the treatment of spinal cord injury. Additionally, the manufacturing route may be configured to produce in-vitro 3D cell based model of spinal cord injury to aid drug development and enhance prosthesis performance. The goal of this investigation was to optimise the multi-layer scaffold design parameters for prosthesis manufacture, to enable the development of multi-layer patient specific implant therapies. The work has also focused on the fabricating aligned nanofibre scaffolds that promote in-vitro neuronal and glial cell population growth, cell-to-cell interaction and long-term survival following trauma to mimic an in-vivo spinal cord lesion. The approach has established reproducible lesions and has identified markers of trauma and regeneration marked by effective neuronal migration across the lesion with glial support. The investigation has advanced the development of an in-vitro model of traumatic spinal cord injury and has identified a route to manufacture prostheses which target the repair spinal cord injury. Evidence collated to investigate the multi-layer concept suggests that physical cues provided by nanofibres provide both a natural extra-cellular matrix (ECM) like environment and controls cell proliferation and migration. Specifically, aligned nanofibre layers act as a guidance system for migrating and elongating neurons. On a larger scale, material type in multi-layer systems also has an influence in inter-layer migration as cell types favour different material types. Results have shown that layering nanofibre membranes create a multi-level scaffold system which can enhance or prohibit cell migration between layers. It is hypothesised that modifying nanofibre layer material permits control over neuronal/glial cell migration. Using this concept, layering of neuronal and glial cells has become possible, in the context of tissue engineering and also modelling in-vitro induced lesions.

Keywords: electrospinning, layering, lesion, modeling, nanofibre

Procedia PDF Downloads 136

Authors: J. Yan, B. Pieper, B. Bucsky, H. H. Sievers, B. Nasseri, S. A. Mohamed

Abstract:

In order to optimize the efficacy of medications, the regular follow-up with long-term continuous monitoring of heart rhythmic patterns has been facilitated since clinical introduction of cardiac implantable electronic monitoring devices (CIMD). Extensive analysis of rhythmic circadian properties is capable to disclose the distributions of arrhythmic events, which may support appropriate medication according rate-/rhythm-control strategy and minimize consequent afflictions. 348 patients (69 ± 0.5ys, male 61.8%) with predisposed atrial fibrillation (AF), undergoing primary ablating therapies combined to coronary or valve operations and secondary implantation of CIMDs, were involved and divided into 3 groups such as PAAF (paroxysmal AF) (n=99, male 68.7%), PEAF (persistent AF) (n=94, male 62.8%), and LSPEAF (long-standing persistent AF) (n=155, male 56.8%). All patients participated in three-year ambulant follow-up (3, 6, 9, 12, 18, 24, 30 and 36 months). Burdens of atrial fibrillation recurrence were assessed using cardiac monitor devices, whereby attacks frequencies and their circadian patterns were systemically analyzed. Anticoagulants and regular anti-arrhythmic medications were evaluated and the last were listed in terms of anti-rate and anti-rhythm regimens. Patients in the PEAF-group showed the least AF-burden after surgical ablating procedures compared to both of the other subtypes (p < 0.05). The AF-recurrences predominantly performed such attacks’ property as shorter than one hour, namely within 10 minutes (p < 0.05), regardless of AF-subtypes. Concerning circadian distribution of the recurrence attacks, frequent AF-attacks were mostly recorded in the morning in the PAAF-group (p < 0.05), while the patients with predisposed PEAF complained less attack-induced discomforts in the latter half of the night and the ones with LSPEAF only if they were not physically active after primary surgical ablations. Different AF-subtypes presented distinct therapeutic efficacies after appropriate surgical ablating procedures and recurrence properties in sense of circadian distribution. An optimization of medical regimen and drug dosages to maintain the therapeutic success needs more attention to detailed assessment of the long-term follow-up. Rate-control strategy plays a much more important role than rhythm-control in the ongoing follow-up examinations.

Keywords: atrial fibrillation, CIMD, MAZE, rate-control, rhythm-control, rhythm patterns

Procedia PDF Downloads 156

Authors: Kanika Gupta, Ashok Kumar

Abstract:

Biofilms are dense, highly hydrated cell clusters that are irreversibly attached to a substratum, to an interface or to each other, and are embedded in a self-produced gelatinous matrix composed of extracellular polymeric substances. Research in biofilm field has become very significant, as biofilm has shown high mechanical resilience and resistance to antibiotic treatment and constituted as a significant problem in both healthcare and other industry related to microorganisms. The massive information both stated and hidden in the biofilm literature are growing exponentially therefore it is not possible for researchers and practitioners to automatically extract and relate information from different written resources. So, the current work proposes and discusses the use of text mining techniques for the extraction of information from biofilm literature corpora containing 34306 documents. It is very difficult and expensive to obtain annotated material for biomedical literature as the literature is unstructured i.e. free-text. Therefore, we considered unsupervised approach, where no annotated training is necessary and using this approach we developed a system that will classify the text on the basis of growth and development, drug effects, radiation effects, classification and physiology of biofilms. For this, a two-step structure was used where the first step is to extract keywords from the biofilm literature using a metathesaurus and standard natural language processing tools like Rapid Miner_v5.3 and the second step is to discover relations between the genes extracted from the whole set of biofilm literature using pubmed.mineR_v1.0.11. We used unsupervised approach, which is the machine learning task of inferring a function to describe hidden structure from 'unlabeled' data, in the above-extracted datasets to develop classifiers using WinPython-64 bit_v3.5.4.0Qt5 and R studio_v0.99.467 packages which will automatically classify the text by using the mentioned sets. The developed classifiers were tested on a large data set of biofilm literature which showed that the unsupervised approach proposed is promising as well as suited for a semi-automatic labeling of the extracted relations. The entire information was stored in the relational database which was hosted locally on the server. The generated biofilm vocabulary and genes relations will be significant for researchers dealing with biofilm research, making their search easy and efficient as the keywords and genes could be directly mapped with the documents used for database development.

Keywords: biofilms literature, classifiers development, text mining, unsupervised learning approach, unstructured data, relational database

Procedia PDF Downloads 169

Authors: Jae-Hyeon Kim, Michael Lee

Abstract:

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 323

Authors: Paresh Patel, Priya Patel, Vaidehi Sorathiya, Navin Sheth

Abstract:

The aim of present work was to fabricate Salmeterol Xinafoate (SX) metered dose inhaler (MDI) for asthma and to evaluate the SX loaded solid lipid nanoparticles (SLNs) for pulmonary delivery. Solid lipid nanoparticles can be used to deliver particles to the lungs via MDI. A modified solvent emulsification diffusion technique was used to prepare Salmeterol Xinafoate loaded solid lipid nanoparticles by using compritol 888 ATO as lipid, tween 80 as surfactant, D-mannitol as cryoprotecting agent and L-leucine was used to improve aerosolization behaviour. Box-Behnken design was applied with 17 runs. 3-D surface response plots and contour plots were drawn and optimized formulation was selected based on minimum particle size and maximum % EE. % yield, in vitro diffusion study, scanning electron microscopy, X-ray diffraction, DSC, FTIR also characterized. Particle size, zeta potential analyzed by Zetatrac particle size analyzer and aerodynamic properties was carried out by cascade impactor. Pre convulsion time was examined for control group, treatment group and compare with marketed group. MDI was evaluated for leakage test, flammability test, spray test and content per puff. By experimental design, particle size and % EE found to be in range between 119-337 nm and 62.04-76.77% by solvent emulsification diffusion technique. Morphologically, particles have spherical shape and uniform distribution. DSC & FTIR study showed that no interaction between drug and excipients. Zeta potential shows good stability of SLNs. % respirable fraction found to be 52.78% indicating reach to the deep part of lung such as alveoli. Animal study showed that fabricated MDI protect the lungs against histamine induced bronchospasm in guinea pigs. MDI showed sphericity of particle in spray pattern, 96.34% content per puff and non-flammable. SLNs prepared by Solvent emulsification diffusion technique provide desirable size for deposition into the alveoli. This delivery platform opens up a wide range of treatment application of pulmonary disease like asthma via solid lipid nanoparticles.

Keywords: salmeterol xinafoate, solid lipid nanoparticles, box-behnken design, solvent emulsification diffusion technique, pulmonary delivery

Procedia PDF Downloads 450

Authors: S. G. Vasantharaju, Viswanath Guptha, Raghavendra Shetty

Abstract:

Introduction: Aminophylline is a methylxanthine derivative belonging to the class bronchodilator. From the literature survey, reported methods reveals the solid phase extraction and liquid liquid extraction which is highly variable, time consuming, costly and laborious analysis. Present work aims to develop a simple, highly sensitive, precise and accurate high-performance liquid chromatography method for the quantification of Aminophylline in rat plasma samples which can be utilized for preclinical studies. Method: Reverse Phase high-performance liquid chromatography method. Results: Selectivity: Aminophylline and the internal standard were well separated from the co-eluted components and there was no interference from the endogenous material at the retention time of analyte and the internal standard. The LLOQ measurable with acceptable accuracy and precision for the analyte was 0.5 µg/mL. Linearity: The developed and validated method is linear over the range of 0.5-40.0 µg/mL. The coefficient of determination was found to be greater than 0.9967, indicating the linearity of this method. Accuracy and precision: The accuracy and precision values for intra and inter day studies at low, medium and high quality control samples concentrations of aminophylline in the plasma were within the acceptable limits Extraction recovery: The method produced consistent extraction recovery at all 3 QC levels. The mean extraction recovery of aminophylline was 93.57 ± 1.28% while that of internal standard was 90.70 ± 1.30%. Stability: The results show that aminophylline is stable in rat plasma under the studied stability conditions and that it is also stable for about 30 days when stored at -80˚C. Pharmacokinetic studies: The method was successfully applied to the quantitative estimation of aminophylline rat plasma following its oral administration to rats. Discussion: Preclinical studies require a rapid and sensitive method for estimating the drug concentration in the rat plasma. The method described in our article includes a simple protein precipitation extraction technique with ultraviolet detection for quantification. The present method is simple and robust for fast high-throughput sample analysis with less analysis cost for analyzing aminophylline in biological samples. In this proposed method, no interfering peaks were observed at the elution times of aminophylline and the internal standard. The method also had sufficient selectivity, specificity, precision and accuracy over the concentration range of 0.5 - 40.0 µg/mL. An isocratic separation technique was used underlining the simplicity of the presented method.

Keywords: Aminophyllin, preclinical pharmacokinetics, rat plasma, RPHPLC

Procedia PDF Downloads 220

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

Procedia PDF Downloads 103

Authors: Manohar Salla, Mark S. Butler, Ruby Pelingon, Geraldine Kaeslin, Daniel E. Croker, Janet C. Reid, Jong Min Baek, Paul V. Bernhardt, Elizabeth M. J. Gillam, Matthew A. Cooper, Avril A. B. Robertson

Abstract:

MCC950 is a potent and selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome that shows early promise for treatment of inflammatory diseases. The identification of major metabolites of lead molecule is an important step during drug development process. It provides an information about the metabolically labile sites in the molecule and thereby helping medicinal chemists to design metabolically stable molecules. To identify major metabolites of MCC950, the compound was incubated with human liver microsomes and subsequent analysis by (+)- and (−)-QTOF-ESI-MS/MS revealed a major metabolite formed due to hydroxylation on 1,2,3,5,6,7-hexahydro-s-indacene moiety of MCC950. This major metabolite can lose two water molecules and three possible regioisomers were synthesized. Co-elution of major metabolite with each of the synthesized compounds using HPLC-ESI-SRM-MS/MS revealed the structure of the metabolite (±) N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. Subsequent synthesis of individual enantiomers and coelution in HPLC-ESI-SRM-MS/MS using a chiral column revealed the metabolite was R-(+)- N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. To study the possible cytochrome P450 enzyme(s) responsible for the formation of major metabolite, MCC950 was incubated with a panel of cytochrome P450 enzymes. The result indicated that CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2J2 and CYP3A4 are most likely responsible for the formation of the major metabolite. The biological activity of the major metabolite and the other synthesized regioisomers was also investigated by screening for for NLRP3 inflammasome inhibitory activity and cytotoxicity. The major metabolite had 170-fold less inhibitory activity (IC50-1238 nM) than MCC950 (IC50-7.5 nM). Interestingly, one regioisomer had shown nanomolar inhibitory activity (IC50-232 nM). However, no evidence of cytotoxicity was observed with any of these synthesized compounds when tested in human embryonic kidney 293 cells (HEK293) and human liver hepatocellular carcinoma G2 cells (HepG2). These key findings give an insight into the SAR of the hexahydroindacene moiety of MCC950 and reveal a metabolic soft spot which could be blocked by chemical modification.

Keywords: Cytochrome P450, inflammasome, MCC950, metabolite, microsome, NLRP3

Procedia PDF Downloads 250

Authors: Abeer Y. Ibrahim, Faten M. Ibrahim, Samah A. El-Newary, Saber F. Hendawy

Abstract:

Objective: Appreciation of in-vitro anti-inflammatory and antioxidant characters of Vitex agnus-castus berries alcoholic extract and fractions, as well as in-vivo antitumor ability of alcoholic extract and chloroform fraction against Ehrlich ascites carcinoma is the aim of this study. Material and methods: Antioxidant properties of crude alcoholic extract of vitex berries as well as petroleum ether, chloroform, ethyl acetate and butanol fractions were evaluated, in-vitro assessments, as compared with standard materials, l-ascorbic acid (vitamin C) and butylated hydroxyl toluene(BHT). The anti-inflammatory activity was investigated in cyclooxygenase (COX)-1 and COX-2 inhibition assays. Moreover, in-vivo antitumor effect of vitex berries alcoholic and chloroform extracts were evaluated using Ehrlich ascites carcinoma model. Data were presented as mean±SE, and data were analyzed by one-way analysis of variance test. Results and conclusion: Berries crude extract showed potent antioxidant activity followed with its fractions ethyl acetate and chloroform as compared with standard (V.C and BHT). Ethyl acetate fraction showed good reduction capability, metal ion chelation, hydrogen peroxide scavenging, nitric oxide scavenging and superoxide anion scavenging. Meanwhile, chloroform fraction produced the highest free radical scavenging activity and total antioxidant capacity. In respectable of lipid peroxidation inhibition, crude alcoholic extract and its fractions cleared weak inhibition in comparing with standard materials. Anti-inflammatory activity of V. agnus-castus berries chloroform fraction of vitex was best COX-2 inhibitor (IC₅₀, 135.41 µg/ ml) as compared to vitex alcoholic extract or ethyl acetate fraction with weak inhibitory effect on COX-1 (IC50, 778.432 µg/ ml), where the lowest effect on COX-1 was recorded with alcoholic extract. Alcoholic extract and its fractions showed weak COX-1 inhibition activity, whereas COX-2 was inhibited (100%), compared with celecoxib drug (72% at 1000ppm). The crude alcoholic and chloroform extracts of V. agnus-castus barries significantly reduced the viable Ehrlich cell count and increased nonviable count with amelioration of all hematological parameters. This amelioration was reflected on increasing median survival time and significant increase (P < 0.05) in lifespan.

Keywords: anti-inflammatory, antioxidants, ehrlich ascites carcinoma, Vitex agnus-castus

Procedia PDF Downloads 144

Authors: K. Graniczkowska, N. Beloglazova, S. De Saeger

Abstract:

The threat of synthetic drugs is one of the most significant current drug problems worldwide. The use of drugs of abuse has increased dramatically during the past three decades. Among others, Amphetamine-Type Stimulants (ATS) are globally the second most widely used drugs after cannabis, exceeding the use of cocaine and heroin. ATS are potent central nervous system (CNS) stimulants, capable of inducing euphoric static similar to cocaine. Recreational use of ATS is widespread, even though warnings of irreversible damage of the CNS were reported. ATS pose a big problem and their production contributes to the pollution of the environment by discharging big volumes of liquid waste to sewage system. Therefore, there is a demand to develop robust and sensitive sensors that can detect ATS and their intermediates in environmental water samples. A rapid and simple test is required. Analysis of environmental water samples (which sometimes can be a harsh environment) using antibody-based tests cannot be applied. Therefore, molecular imprinted polymers (MIPs), which are known as synthetic antibodies, have been chosen for that approach. MIPs are characterized with a high mechanical and thermal stability, show chemical resistance in a broad pH range and various organic or aqueous solvents. These properties make them the preferred type of receptors for application in the harsh conditions imposed by environmental samples. To the best of our knowledge, there are no existing MIPs-based sensors toward amphetamine and its intermediates. Also not many commercial MIPs for this application are available. Therefore, the aim of this study was to compare different techniques to obtain MIPs with high specificity towards ATS and characterize them for following use in a sensing unit. MIPs against amphetamine and its intermediates were synthesized using a few different techniques, such as electro-, thermo- and UV-initiated polymerization. Different monomers, cross linkers and initiators, in various ratios, were tested to obtain the best sensitivity and polymers properties. Subsequently, specificity and selectivity were compared with commercially available MIPs against amphetamine. Different linkers, such as lipoic acid, 3-mercaptopioponic acid and tyramine were examined, in combination with several immobilization techniques, to select the best procedure for attaching particles on sensor surface. Performed experiments allowed choosing an optimal method for the intended sensor application. Stability of MIPs in extreme conditions, such as highly acidic or basic was determined. Obtained results led to the conclusion about MIPs based sensor applicability in sewage system testing.

Keywords: amphetamine type stimulants, environment, molecular imprinted polymers, MIPs, sensor

Procedia PDF Downloads 249

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

Abstract:

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

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Authors: Emma Plante, Charles Ekwunwa, Diego Illanes

Abstract:

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

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Authors: Victoria Eugenia Garnacho-Garnacho, Elena Sonsoles Rodriguez-Lopez, Raquel Delgado-Delgado, Alvaro Otero-Campos, Jesus Guodemar-Perez, Angelo Michelle Vagali, Juan Pablo Hervas-Perez

Abstract:

Asthma is a heterogeneous disease which has always had a drug treatment. Osteopathic treatment that we propose is aimed, seen through a dorsal manipulation (Dog Technic D1-D4) and a technique for diaphragm (Longitudinal Stroke) forced expiratory flow in spirometry changes there are in particular that there is an increase in the volumes of the Peak Flow and Post intervention and effort and that the application of these two techniques together is more powerful if we applied only a Longitudinal (Stroke). Also rating if this type of treatment will have repercussions on breathlessness, a very common symptom in asthma. And finally to investigate if provided vertebra pain decreased after a manipulation. Methods—Participants were recruited between students and professors of the University, aged 18-65, patients (n = 18) were assigned randomly to one of the two groups, group 1 (longitudinal Stroke and manipulation dorsal Dog Technic) and group 2 (diaphragmatic technique, Longitudinal Stroke). The statistical analysis is characterized by the comparison of the main indicator of obstruction of via area PEF (peak expiratory flow) in various situations through the peak flow meter Datospir Peak-10. The measurements were carried out in four phases: at rest, after the stress test, after the treatment, after treatment and the stress test. After each stress test was evaluated, through the Borg scale, the level of Dyspnea on each patient, regardless of the group. In Group 1 in addition to these parameters was calculated using an algometer spinous pain before and after the manipulation. All data were taken at the minute. Results—12 Group 1 (Dog Technic and Longitudinal Stroke) patients responded positively to treatment, there was an increase of 5.1% and 6.1% of the post-treatment PEF and post-treatment, and effort. The results of the scale of Borg by which we measure the level of Dyspnea were positive, a 54.95%, patients noted an improvement in breathing. In addition was confirmed through the means of both groups group 1 in which two techniques were applied was 34.05% more effective than group 2 in which applied only a. After handling pain fell by 38% of the cases. Conclusions—The impact of the technique of Dog-Technic for D1-D4 and the Longitudinal Stroke technique for diaphragm in the volumes of peak expiratory flow (PEF) in asthmatic patients were positive, there was a change of the PEF Post intervention and post-treatment, and effort and showed the most effective group in which only a technique was applied. Furthermore this type of treatment decreased facilitated vertebrae pain and was efficient in the improvement of Dyspnea and the general well-being of the patient.

Keywords: ANS, asthma, manipulation, manual therapy, osteopathic

Procedia PDF Downloads 286