Search results for: cancer drug

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

Abstract:

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

Procedia PDF Downloads 500

Authors: Raphael Udeh, Luis García De Guadiana Romualdo, Xenia Dolje-Gore

Abstract:

Background: Quite disturbing is the huge public health impact of COVID-19: As at today [25th March 2021, the COVID-19 global burden shows over 123 million cases and over 2.7 million deaths worldwide. Rationale: Recent evidence shows calprotectin’s potential as a therapeutic target, stating that tasquinimod, from the Quinoline-3-Carboxamide family is capable of blocking the interaction between calprotectin and TLR4. Hence preventing the cytokine release syndrome, that heralds the functional exhaustion in COVID-19. Early preclinical studies showed that tasquinimod inhibit tumor growth and prevent angiogenesis/cytokine storm. Phase I – III clinical studies in prostate cancer showed it has a good safety profile with good radiologic progression free survival but no effect on overall survival. Rationale/hypothesis: Strategic endeavors have been amplified globally to assess new therapeutic interventions for COVID-19 management – thus the clinical and antiviral efficacy of tasquinimod in COVID-19 remains to be explored. Hence the primary objective of this trial will be to evaluate the efficacy of tasquinimod in the treatment of adult patients with severe COVID-19 infections. Therefore, I hypothesise that among adults with COVID19 infection, tasquinimod will reduce the severe respiratory distress associated with COVID-19 compared to placebo, over a 28-day study period. Method: The setting is in Europe. Design – a randomized, placebo-controlled, phase II double-blinded trial. Trial lasts for 28 days from randomization, Tasquinimod capsule given as 0.5mg daily 1st fortnight, then 1mg daily 2nd fortnight. I0 outcome - assessed using six-point ordinal scale alongside eight 20 outcomes. 125 participants to be enrolled, data collection at baseline and subsequent data points, and safety reporting monitored via serological profile. Significance: This work could potentially establish tasquinimod as an effective and safe therapeutic agent for COVID-19 by reducing the severe respiratory distress, related time to recovery, time on oxygen/admission. It will also drive future research – as in larger multi-centre RCT.

Keywords: Calprotectin, COVID-19, Phase II Trial, Tasquinimod

Procedia PDF Downloads 171

Authors: Kseniia Zviagintseva, Brett Buttliere

Abstract:

Science is fundamentally a problem-solving enterprise, and scientists pay more attention to the negative things, that cause them dissonance and negative affective state of uncertainty or contradiction. While this is agreed upon by philosophers of science, there are few empirical demonstrations. Here we examine the keywords from those papers published by PLoS in 2014 and show with several sentiment analyzers that negative keywords are studied more than positive keywords. Our dataset is the 927,406 keywords of 32,870 scientific articles in all fields published in 2014 by the journal PLOS ONE (collected from Altmetric.com). Counting how often the 47,415 unique keywords are used, we can examine whether those negative topics are studied more than positive. In order to find the sentiment of the keywords, we utilized two sentiment analysis tools, Hu and Liu (2004) and SentiStrength (2014). The results below are for Hu and Liu as these are the less convincing results. The average keyword was utilized 19.56 times, with half of the keywords being utilized only 1 time and the maximum number of uses being 18,589 times. The keywords identified as negative were utilized 37.39 times, on average, with the positive keywords being utilized 14.72 times and the neutral keywords - 19.29, on average. This difference is only marginally significant, with an F value of 2.82, with a p of .05, but one must keep in mind that more than half of the keywords are utilized only 1 time, artificially increasing the variance and driving the effect size down. To examine more closely, we looked at those top 25 most utilized keywords that have a sentiment. Among the top 25, there are only two positive words, ‘care’ and ‘dynamics’, in position numbers 5 and 13 respectively, with all the rest being identified as negative. ‘Diseases’ is the most studied keyword with 8,790 uses, with ‘cancer’ and ‘infectious’ being the second and fourth most utilized sentiment-laden keywords. The sentiment analysis is not perfect though, as the words ‘diseases’ and ‘disease’ are split by taking 1st and 3rd positions. Combining them, they remain as the most common sentiment-laden keyword, being utilized 13,236 times. More than just splitting the words, the sentiment analyzer logs ‘regression’ and ‘rat’ as negative, and these should probably be considered false positives. Despite these potential problems, the effect is apparent, as even the positive keywords like ‘care’ could or should be considered negative, since this word is most commonly utilized as a part of ‘health care’, ‘critical care’ or ‘quality of care’ and generally associated with how to improve it. All in all, the results suggest that negative concepts are studied more, also providing support for the notion that science is most generally a problem-solving enterprise. The results also provide evidence that negativity and contradiction are related to greater productivity and positive outcomes.

Keywords: bibliometrics, keywords analysis, negativity bias, positive and negative words, scientific papers, scientometrics

Procedia PDF Downloads 164

Authors: Siti Aisya Gany, Swee Ching Tan, Sook Yee Gan

Abstract:

Diminished antioxidant defense or increased production of reactive oxygen species in the biological system can result in oxidative stress which may lead to various neurodegenerative diseases including Alzheimer’s disease (AD). Microglial activation also contributes to the progression of AD by producing several pro-inflammatory cytokines, nitric oxide (NO), and prostaglandin E2 (PGE2). Oxidative stress and inflammation have been reported to be possible pathophysiological mechanisms underlying AD. In addition, the cholinergic hypothesis postulates that memory impairment in patient with AD is also associated with the deficit of cholinergic function in the brain. Although a number of drugs have been approved for the treatment of AD, most of these synthetic drugs have diverse side effects and yield relatively modest benefits. Marine algae have great potential in pharmaceutical and biomedical applications as they are valuable sources of bioactive properties such as anti-coagulation, anti-microbial, anti-oxidative, anti-cancer and anti-inflammatory. Hence, this study aimed to provide an overview of the properties of Malaysian seaweeds (Padina australis, Sargassum polycystum and Caulerpa racemosa) in inhibiting oxidative stress, neuroinflammation and cholinesterase enzymes. All tested samples significantly exhibit potent DPPH and moderate Superoxide anion radical scavenging ability (P<0.05). Hexane and methanol extracts of S. polycystum exhibited the most potent radical scavenging ability with IC50 values of 0.1572 ± 0.004 mg/ml and 0.8493 ± 0.02 for DPPH and ABTS assays, respectively. Hexane extract of C. racemosa gave the strongest superoxide radical inhibitory effect (IC50 of 0.3862± 0.01 mg/ml). Most seaweed extracts significantly inhibited the production of cytokine (IL-6, IL-1 β, TNFα) and NO in a concentration-dependent manner without causing significant cytotoxicity to the lipopolysaccharide (LPS)-stimulated microglia cells (P<0.05). All extracts suppressed cytokine and NO level by more than 80% at the concentration of 0.4mg/ml. In addition, C. racemosa and S. polycystum also showed anti-acetylcholinesterase activities with the IC50 values ranging from 0.086-0.115 mg/ml. Moreover, C. racemosa and P. australis were also found to be active against butyrylcholinesterase with IC50 values ranging from 0.118-0.287 mg/ml.

Keywords: anti-cholinesterase, anti-oxidative, neuroinflammation, seaweeds

Procedia PDF Downloads 642

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

Abstract:

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

Procedia PDF Downloads 106

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

Abstract:

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

Procedia PDF Downloads 272

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

Abstract:

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

Procedia PDF Downloads 402

Authors: Sarai Guerrero, Lijia Liu

Abstract:

Zinc gallogermanate (ZGGO) is a persistent phosphor that can emit in the near infrared (NIR) range once dopped with Cr³⁺ enabling its use for in-vivo deep-tissue bio-imaging. Such a property also allows for its application in cancer diagnosis and therapy. Given this, work into developing a synthetic procedure that can be done using common laboratory instruments and equipment as well as understanding ZGGO overall, is in demand. However, the ZGGO nanoparticles must have a size compatible for cell intake to occur while still maintaining sufficient photoluminescence. The nanoparticle must also be made biocompatible by functionalizing the surface for hydrophilic solubility and for high particle uniformity in the final product. Additionally, most research is completed on doped ZGGO, leaving a gap in understanding the base form of ZGGO. It also leaves a gap in understanding how doping affects the synthesis of ZGGO. In this work, the first step of optimizing the particle size via the crystalline size of ZGGO was done with undoped ZGGO using the organic acid, oleic acid (OA) for organic ligand-assisted biphasic hydrothermal synthesis. The effects of this synthesis procedure on ZGGO’s crystallinity were evaluated using Powder X-Ray Diffraction (PXRD). OA was selected as the capping ligand as experiments have shown it beneficial in synthesizing sub-10 nm zinc gallate (ZGO) nanoparticles as well as palladium nanocrystals and magnetite (Fe₃O₄) nanoparticles. Later it is possible to substitute OA with a different ligand allowing for hydrophilic solubility. Attenuated Total Reflection Fourier-Transform Infrared (ATR-FTIR) was used to investigate the surface of the nanoparticle to investigate and verify that OA had capped the nanoparticle. PXRD results showed that using this procedure led to improved crystallinity, comparable to the high-purity reagents used on the ZGGO nanoparticles. There was also a change in the crystalline size of the ZGGO nanoparticles. ATR-FTIR showed that once capped ZGGO cannot be annealed as doing so will affect the OA. These results point to this new procedure positively affecting the crystallinity of ZGGO nanoparticles. There are also repeatable implying the procedure is a reliable source of highly crystalline ZGGO nanoparticles. With this completed, the next step will be working on substituting the OA with a hydrophilic ligand. As these ligands effect the solubility of the nanoparticle as well as the pH that the nanoparticles can dissolve in, further research is needed to verify which ligand is best suited for preparing ZGGO for bio-imaging.

Keywords: biphasic hydrothermal synthesis, crystallinity, oleic acid, zinc gallogermanate

Procedia PDF Downloads 104

Authors: Sanjay Singh, Parameswara Rao Vuddanda

Abstract:

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

Procedia PDF Downloads 363

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

Abstract:

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

Procedia PDF Downloads 68

Authors: Diea Gamal Abo El-Hassan, Salwa Ahmed Aly, Abdelrahman Mahmoud Abdelgwad

Abstract:

The major conjugated linoleic acid (CLA) isomers have anticancer effect, especially breast cancer cells, inhibits cell growth and induces cell death. Also, CLA has several health benefits in vivo, including antiatherogenesis, antiobesity, and modulation of immune function. The present study aimed to assess the safety and anticancer effects of milk fat CLA against in vivo Ehrlich ascites carcinoma (EAC) in female Swiss albino mice. This was based on acute toxicity study, detection of the tumor growth, life span of EAC bearing hosts, and simultaneous alterations in the hematological, biochemical, and histopathological profiles. Materials and Methods: One hundred and fifty adult female mice were equally divided into five groups. Groups (1-2) were normal controls, and Groups (3-5) were tumor transplanted mice (TTM) inoculated intraperitoneally with EAC cells (2×106 /0.2 mL). Group (3) was (TTM positive control). Group (4) TTM fed orally on balanced diet supplemented with milk fat CLA (40 mg CLA/kg body weight). Group (5) TTM fed orally on balanced diet supplemented with the same level of CLA 28 days before tumor cells inoculation. Blood samples and specimens from liver and kidney were collected from each group. The effect of milk fat CLA on the growth of tumor, life span of TTM, and simultaneous alterations in the hematological, biochemical, and histopathological profiles were examined. Results: For CLA treated TTM, significant decrease in tumor weight, ascetic volume, viable Ehrlich cells accompanied with increase in life span were observed. Hematological and biochemical profiles reverted to more or less normal levels and histopathology showed minimal effects. Conclusion: The present study proved the safety and anticancer efficiency of milk fat CLA and provides a scientific basis for its medicinal use as anticancer attributable to the additive or synergistic effects of its isomers.

Keywords: anticancer activity, conjugated linoleic acid, Ehrlich ascites carcinoma, % increase in life span, mean survival time, tumor transplanted mice.

Procedia PDF Downloads 65

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 43

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 632

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 64

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 36

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 105

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 131

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 144

Authors: Noury Bakrim

Abstract:

From the point of view of language morphodynamics, interpretative Readability of the text-result (the stasis) is not the external hermeneutics of its various potential reading events but the paradigmatic, semantic immanence of its dynamics. In other words, interpretative Readability articulates the potential tension between projection (intentionality of the discursive event) and the result (Readability within the syntagmatic stasis). We then consider that translation represents much more a metalinguistic conversion of neurocognitive bilingual sub-routines and modular relations than a semantic equivalence. Furthermore, the actualizing Readability (the process of rewriting a target text within a target language/genre) builds upon the descriptive level between the generative syntax/semantic from and its paradigmatic potential translatability. Translation corpora reveal the evidence of a certain focusing on the positivist stasis of the source text at the expense of its interpretative Readability. For instance, Fluchere's brilliant translation of Miller's Tropic of cancer into French realizes unconsciously an inversion of the hierarchical relations between Life Thought and Fable: From Life Thought (fable) into Fable (Life Thought). We could regard the translation of Bernard Kreiss basing on Canetti's work die englischen Jahre (les annees anglaises) as another inversion of the historical scale from individual history into Hegelian history. In order to describe and test both translation process and result, we focus on the pedagogical practice which enables various principles grounding in interpretative/actualizing Readability. Henceforth, establishing the analytical uttering dynamics of the source text could be widened by other practices. The reversibility test (target - source text) or the comparison with a second translation in a third language (tertium comparationis A/B and A/C) point out the evidence of an impossible event. Therefore, it doesn't imply an uttering idealistic/absolute source but the irreducible/non-reproducible intentionality of its production event within the experience of world/discourse. The aim of this paper is to conceptualize translation as the tension between interpretative and actualizing Readability in a new approach grounding in morphodynamics of language and Translatability (mainly into French) within literary and non-literary texts articulating theoretical and described pedagogical corpora.

Keywords: readability, translation as deverbalization, translation as conversion, Tertium Comparationis, uttering actualization, translation pedagogy

Procedia PDF Downloads 144

Authors: Malika Turganova, Aigul Abduldayeva

Abstract:

Modern conditions require nursing innovations at the primary ambulatory stage in the health system of Kazakhstan. There is a growing need for nurses involved in before-doctor attendance for preventive interview with a female population about reproductive health. We conducted questionnaire survey of the population of Astana in 2015. Questionnaires were drawn up according to the criteria of sexual health of World Health Organization. 3593 respondents out of 8000 questionnaires agreed to answer the questions anonymously, mM=±2,1. The average age of women comprised 37,4±11,2, Ме=31,7 years of age. Analysis of awareness about marriage hygiene revealed that 72,7% of respondents did not receive information about marriage hygiene and 89,1% respondents consider it more advisable before marriage. 45,9% of respondents specified the internet as a source of information on marriage hygiene issues, 24,5% of respondents pointed out friends, and 21,5% specified doctor. Comparing female age groups under and after 40 years old we see that proportion of cases when parents provide information about marriage hygiene issues comprises 4.3% (χ2 =9.8, p<0.05). The most important factor of preservation of women reproductive health is handling a problem of unwanted pregnancy. The responsibility lies equally in men and women. Data analysis of contraceptive methods by ranking showed three most frequently used methods: contraception sheath – 29.3%, then coitus interruptus – 18.7% and hormonal preparations – 16.9%. The most important factor of women's reproductive health preservation is a solving of the problem of unwanted pregnancy, and in this respect, the responsibility lies equally in men and women. Analyzing obtained data on contraceptive methods by ranking three of the most frequently used methods are condoms – 29,3%, then coitus interruptus – 18,7% and hormonal preparations – 16,9%. Additional oral survey of the population showed a low level of informational support of female population by family physicians, health care professionals of educational organizations (schools, universities, and colleges) about hormonal contraceptive. Females of both age groups used to think that hormonal contraceptives cause collateral damage such as blastoma, cancer, increased body weight, varix dilatation of lower limbs. Satisfaction with the frequency of sexual relations of the respondents comprised 57,6%. At that, women under 40 years of age are the most satisfied women among age groups (χ2 =5,8, p<0,05).

Keywords: nurse, public health service of Kazakhstan, reproductive and sexual health, trust of population

Procedia PDF Downloads 247

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 296

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 423

Authors: Daniela E. Marin, Cornelia Braicu, Gina C. Pistol, Roxana Cojocneanu-Petric, Ioana Berindan Neagoe, Mihail A. Gras, Ionelia Taranu

Abstract:

Aristolochic acid (AA) is a carcinogenic, mutagenic, and nephrotoxic compound commonly found in the Aristolochiaceae family of plants. AA is frequently associated with urothelial carcinoma of the upper urinary tract in human and animals and is considered as being responsible for Balkan Endemic Nephropathy. The pig provides a good animal model because the porcine urological system is very similar to that of humans, both in aspects of physiology and anatomy. MicroRNA (miRNA) are small non-coding RNAs that have an impact on a wide range of biological processes by regulating gene expression at post-transcriptional level. The objective of this study was to analyze the miRNA profiling in the kidneys of AA intoxicated swine. For this purpose, ten TOPIGS-40 crossbred weaned piglets, 4-week-old, male and females with an initial average body weight of 9.83 ± 0.5 kg were studied for 28 days. They were given ad libitum access to water and feed and randomly allotted to one of the following groups: control group (C) or aristolochic acid group (AA). They were fed a maize-soybean-meal-based diet contaminated or not with 0.25mgAA/kg. To profile miRNA in the kidneys of pigs, microarrays and bioinformatics approaches were applied to analyze the miRNA in the kidney of control and AA intoxicated pigs. After normalization, our results have shown that a total of 5 known miRNAs and 4 novel miRNAs had different profiling in the kidney of intoxicated animals versus control ones. Expression of miR-32-5p, miR-497-5p, miR-423-3p, miR-218-5p, miR-128-3p were up-regulated by 0.25mgAA/kg feed, while the expression of miR-9793-5p, miR-9835-3p, miR-9840-3p, miR-4334-5p was down-regulated. The microRNA profiling in kidney of intoxicated animals was associated with modified expression of target genes as: RICTOR, LASP1, SFRP2, DKK2, BMI1, RAF1, IGF1R, MAP2K1, WEE1, HDGF, BCL2, EIF4E etc, involved in cell division cycle, apoptosis, cell differentiation and cell migration, cell signaling, cancer etc. In conclusion, this study provides new data concerning the microRNA profiling in kidney after aristolochic acid intoxications with important implications for human and animal health.

Keywords: aristolochic acid, kidney, microRNA, swine

Procedia PDF Downloads 257

Authors: Amean A. Yasir, Zainab Kh. A. Al-Mahdi Al-Amean

Abstract:

In both developed and developing countries, obesity among women is increasing, but in different patterns and at very different speeds. It may have a negative effect on health, leading to reduced life expectancy and/or increased health problems. This research studied the age distribution among obese women, the types of overweight and obesity, and the extent of the problem of overweight/obesity and the obesity etiological factors among women in Hillah city in central Iraq. A total of 322 overweight and obese women were included in the study, those women were randomly selected. The Body Mass Index was used as indicator for overweight/ obesity. The incidence of overweight/obesity among age groups were estimated, the etiology factors included genetic, environmental, genetic/environmental and endocrine disease. The overweight and obese women were screened for incidence of infection and/or diseases. The study found that the prevalence of 322 overweight and obese women in Hillah city in central Iraq was 19.25% and 80.78%, respectively. The obese women types were recorded based on BMI and WHO classification as class-1 obesity (29.81%), class-2 obesity (24.22%) and class-3 obesity (26.70%), the result was discrepancy non-significant, P value < 0.05. The incidence of overweight in women was high among those aged 20-29 years (90.32%), 6.45% aged 30-39 years old and 3.22% among ≥ 60 years old, while the incidence of obesity was 20.38% for those in the age group 20-29 years, 17.30% were 30-39 years, 23.84% were 40-49 years, 16.92% were 50-59 years group and 21.53% were ≥ 60 years age group. These results confirm that the age can be considered as a significant factor for obesity types (P value < 0.0001). The result also showed that the both genetic factors and environmental factors were responsible for incidents of overweight or obesity (84.78%) p value < 0.0001. The results also recorded cases of different repeated infections (skin infection, recurrent UTI and influenza), cancer, gallstones, high blood pressure, type 2 diabetes, and infertility. Weight stigma and bias generally refers to negative attitudes; Obesity can affect quality of life, and the results of this study recorded depression among overweight or obese women. This can lead to sexual problems, shame and guilt, social isolation and reduced work performance. Overweight and Obesity are real problems among women of all age groups and is associated with the risk of diseases and infection and negatively affects quality of life. This result warrants further studies into the prevalence of obesity among women in Hillah City in central Iraq and the immune response of obese women.

Keywords: obesity, overweight, Iraq, body mass index

Procedia PDF Downloads 364

Authors: Kirill M. Dubovikov, Ekaterina S. Marchenko, Gulsharat A. Baigonakova

Abstract:

NiTi alloys are widely used as implants in medicine due to their unique properties such as superelasticity, shape memory effect and biocompatibility. However, despite these properties, one of the major problems is the release of nickel after prolonged use in the human body under dynamic stress. This occurs due to oxidation and cracking of NiTi implants, which provokes nickel segregation from the matrix to the surface and release into living tissues. As we know, nickel is a toxic element and can cause cancer, allergies, etc. One of the most popular ways to solve this problem is to create a corrosion resistant coating on NiTi. There are many coatings of this type, but not all of them have good biocompatibility, which is very important for medical implants. Coatings based on calcium phosphate phases have excellent biocompatibility because Ca and P are the main constituents of the mineral part of human bone. This fact suggests that a Ca-P coating on NiTi can enhance osteogenesis and accelerate the healing process. Therefore, the aim of this study is to investigate the structure of Ca-P coating on NiTi substrate. Plasma assisted radio frequency (RF) sputtering was used to obtain this film. This method was chosen because it allows the crystallinity and morphology of the Ca-P coating to be controlled by the sputtering parameters. It allows us to obtain three different NiTi samples with Ca-P coating. XRD, AFM, SEM and EDS were used to study the composition, structure and morphology of the coating phase. Scratch tests were carried out to evaluate the adhesion of the coating to the substrate. Wettability tests were used to investigate the hydrophilicity of the different coatings and to suggest which of them had better biocompatibility. XRD showed that the coatings of all samples were hydroxyapatite, but the matrix was represented by TiNi intermetallic compounds such as B2, Ti2Ni and Ni3Ti. The SEM shows that the densest and defect-free coating has only one sample after three hours of sputtering. Wettability tests show that the sample with the densest coating has the lowest contact angle of 40.2° and the largest free surface area of 57.17 mJ/m2, which is mostly disperse. A scratch test was carried out to investigate the adhesion of the coating to the surface and it was shown that all coatings were removed by a cohesive mechanism. However, at a load of 30N, the indenter reached the substrate in two out of three samples, except for the sample with the densest coating. It was concluded that the most promising sputtering mode was the third, which consisted of three hours of deposition. This mode produced a defect-free Ca-P coating with good wettability and adhesion.

Keywords: biocompatibility, calcium phosphate coating, NiTi alloy, radio frequency sputtering.

Procedia PDF Downloads 48

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 197

Authors: Amrit Vasdev, Edwin Rho, Gurinder Vasdev

Abstract:

Robotic surgery has enabled a new spectrum of minimally invasive breast reconstruction by improving visualization, surgeon posturing, and improved patient outcomes.1 The DaVinci robot system can be utilized in nipple sparing mastectomies and reconstructions. The process involves the insufflation of the subglandular space and a dissection of the mammary gland with a combination of cautery and blunt dissection. This case outlines a 35-year-old woman who has a long-standing family history of breast cancer and a diagnosis of a deleterious BRCA2 genetic mutation. She has decided to proceed with bilateral nipple sparing mastectomies with implants. Her perioperative mammogram and MRI were negative for masses, however, her left internal mammary lymph node was enlarged. She has taken oral contraceptive pills for 3-5 years and denies DES exposure, radiation therapy, human replacement therapy, or prior breast surgery. She does not smoke and rarely consumes alcohol. During the procedure, the patient received a standardized anesthetic for out-patient surgery of propofol infusion, succinylcholine, sevoflurane, and fentanyl. Aprepitant was given as an antiemetic and preoperative Tylenol and gabapentin for pain management. Concerns for the patient during the procedure included CO2 insufflation into the subcutaneous space. With CO2 insufflation, there is a potential for rapid uptake leading to severe acidosis, embolism, and subcutaneous emphysema.2To mitigate this, it is important to hyperventilate the patient and reduce both the insufflation pressure and the CO2 flow rate to the minimal acceptable by the surgeon. For intraoperative monitoring during this 6-9 hour long procedure, it has been suggested to utilize an Arterial-Line for end-tidal CO2 monitoring. However, in this case, it was not necessary as the patient had excellent cardiovascular reserve, and end-tidal CO2 was within normal limits for the duration of the procedure. A BIS monitor was also utilized to reduce anesthesia burden and to facilitate a prompt discharge from the PACU. Minimal Invasive Robotic Surgery will continue to evolve, and anesthesiologists need to be prepared for the new challenges ahead. Based on our limit number of patients, robotic mastectomy appears to be a safe alternative to open surgery with the promise of clearer tissue demarcation and better cosmetic results.

Keywords: anesthesia, mastectomies, robotic, hypercarbia

Procedia PDF Downloads 74

Authors: Isalira Peroba Ramos, Cherley Borba Vieira de Andrade, Grazielle Suhett, Camila Salata, Paulo Cesar Canary, Guilherme Visconde Brasil, Antonio Carlos Campos de Carvalho, Regina Coeli dos Santos Goldenberg

Abstract:

Background: The therapeutic options for patients with cancer now include increasingly complex combinations of medications, radiation therapy (RT), and surgical intervention. Many of these treatments have important potential adverse cardiac effects and are likely to have significant effects on patient outcomes. Cell therapy appears to be promising for the treatment of chronic and degenerative diseases, including cardiomyopathy induced by RT, as the current therapeutic options are insufficient. Aims: To evaluate the potential of bone marrow mesenchymal cells (BMMCs) in radioinduced cardiac damage Methods: Female Wistar rats, 3 months old (Ethics Committee 054/14), were divided into 2 groups, non-treated irradiated group (IR n=15) and irradiated and BMMC treated (IRT n=10). Echocardiography was performed to evaluate heart function. After euthanasia, 3 months post treatment; the left ventricle was removed and prepared for RT-qPCR (VEGF and Pro Collagen I) and histological (picrosirius) analysis. Results: In both groups, 45 days after irradiation, ejection fraction (EF) was in the normal range for these animals (> 70%). However, the BMMC treated group had EF (83.1%±2.6) while the non-treated IR group showed a significant reduction (76.1%±2.6) in relation to the treated group. In addition, we observed an increase in VEGF gene expression and a decrease in Pro Collagen I in IRT when compared to IR group. We also observed by histology that the collagen deposition was reduced in IRT (10.26%±0.83) when compared to IR group (25.29%±0.96). Conclusions: Treatment with BMMCs was able to prevent ejection fraction reduction and collagen deposition in irradiated animals. The increase of VEGF and the decrease of pro collagen I gene expression might explain, at least in part, the cell therapy benefits. All authors disclose no financial or personal relationships with individuals or organizations that could be perceived to bias their work. Sources of funding: FAPERJ, CAPES, CNPq, MCT.

Keywords: mesenchymal cells, radioation, cardiotoxicity, bone marrow

Procedia PDF Downloads 231

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

Abstract:

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 77

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 225