Self-Emulsifying Drug Delivery System for Enhanced Oral Delivery of Tenofovir: Formulation, Physicochemical Characterization, and Bioavailability Assessment.

Tenofovir (TNF) is a common component of many antiretroviral therapy regimens, but it is associated with poor membrane permeability and low oral bioavailability. To improve its oral bioavailability and membrane permeability, a self-emulsifying drug delivery system (SEDDS) was developed and characterized, and its relative bioavailability was compared to the marketed tablets (Tenof). Based on solubility and ternary phase diagram analysis, eucalyptus oil was selected as an oil phase, Kolliphor EL, and Kollisolv MCT 70 were chosen as surfactant and cosurfactant, respectively, while glycerol was used as cosolvent in surfactant mixture. Optimized SEDDS formulation F6 showed an oil droplet size of 98.82 nm and zeta potential of -13.03 mV, indicating the high stability of oil droplets. Differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy characterization studies were also carried out to assess the amorphous and morphological states of the drug in the prepared SEDDS formulation. The in vitro dissolution profile of SEDDS shows the rapid release of the drug. SEDDS F6 demonstrates a higher drug permeability than the plain TNF and TNF-marketed tablets (Tenof). A pharmacokinetic study in rats revealed that SEDDS F6 showed significantly higher Cmax and AUC0-t than the marketed tablets and pure drug suspension. In addition, the relative bioavailability of SEDDS formulation dramatically improved by 21.53-fold compared to marketed tablets and 66.27-fold compared to pure drugs. These findings show that SEDDS composed of eucalyptus oil, glycerol, Kolliphor EL, and Kollisolv MCT 70 could be a useful tool for enhancing physiochemical properties and oral TNF absorption. Therefore, SEDDS has shown promise in improving the oral bioavailability of poorly water-soluble drugs.

Ganoderma lucidum: Insight into antimicrobial and antioxidant properties with development of secondary metabolites.

Ganoderma lucidum is a versatile mushroom. Polysaccharides and triterpenoids are the major bioactive compounds and have been used as traditional medicinal mushrooms since ancient times. They are currently used as nutraceuticals and functional foods. G. lucidum extracts and their bioactive compounds have been used as an alternative to antioxidants and antimicrobial agents. Secondary metabolites with many medicinal properties make it a possible substitute that could be applied as immunomodulatory, anticancer, antimicrobial, anti-oxidant, anti-inflammatory, and anti-diabetic. The miraculous properties of secondary metabolites fascinate researchers for their development and production. Recent studies have paid close attention to the different physical, genetic, biochemical, and nutritional parameters that potentiate the production of secondary metabolites. This review is an effort to collect biologically active constituents from G. lucidum that reveal potential actions against diseases with the latest improvement in a novel technique to get maximum production of secondary metabolites. Studies are going ahead to determine the efficacy of numerous compounds and assess the valuable properties achieved by G. lucidum in favor of antimicrobial and antioxidant outcomes.

Current understanding of structural and molecular changes in diabetic cardiomyopathy.

Diabetic Mellitus has been characterized as the most prevalent disease throughout the globe associated with the serious morbidity and mortality of vital organs. Cardiomyopathy is the major leading complication of diabetes and within this, myocardial dysfunction or failure is the leading cause of the emergency hospital admission. The review is aimed to comprehend the perspectives associated with diabetes-induced cardiovascular complications. The data was collected from several electronic databases such as Google Scholar, Science Direct, ACS publication, PubMed, Springer, etc. using the keywords such as diabetes and its associated complication, the prevalence of diabetes, the anatomical and physiological mechanism of diabetes-induced cardiomyopathy, the molecular mechanism of diabetes-induced cardiomyopathy, oxidative stress, and inflammatory stress, etc. The collected scientific data was screened by different experts based on the inclusion and exclusion criteria of the study. This review findings revealed that diabetes is associated with inefficient substrate utilization, inability to increase glucose metabolism and advanced glycation end products within the diabetic heart resulting in mitochondrial uncoupling, glucotoxicity, lipotoxicity, and initially subclinical cardiac dysfunction and finally in overt heart failure. Furthermore, several factors such as hypertension, overexpression of renin angiotensin system, hypertrophic obesity, etc. have been seen as majorly associated with cardiomyopathy. The molecular examination showed biochemical disability and generation of the varieties of free radicals and inflammatory cytokines and becomes are the substantial causes of cardiomyopathy. This review provides a better understanding of the involved pathophysiology and offers an open platform for discussing and targeting therapy in alleviating diabetes-induced early heart failure or cardiomyopathy.

Impact of Clinical Pharmacist Running Anticoagulation Clinic in Saudi Arabia.

Despite the effectiveness of warfarin in extended anticoagulation, its narrow therapeutic index requires frequent dose adjustments and careful patient monitoring. Thus, we aimed to evaluate the outcomes of clinical pharmacists' intervention in warfarin therapy management in terms of International Normalized Ratio (INR) control, reduction of bleeding, and hospitalization in a tertiary care hospital. An observational retrospective cohort study was conducted on 96 patients taking warfarin therapy in a clinical pharmacist-led anticoagulation clinic. We observed that 39.6% of patients required dose adjustments at their first and second visits. However, dose adjustments during the third, fourth, and fifth weeks were required at 31.1%, 20.8%, and 4.2%, respectively, to achieve INR levels. We also observed that 36.46% of the patients attained the target INR at baseline, which was increased over the first week to the fifth week to 57.29%, 61.46%, 61.46%, 68.75%, and 85.42%, respectively. No one reported the ADR between the third and fifth weeks. Based on our findings, the study strongly suggests that pharmacists' interventions can improve the health-related quality of life of patients undergoing warfarin therapy. Thus, competent pharmacy personnel must be a priority in both usual patient care and critical care among primary care networks.

Beneficial effects of Naringin against lopinavir/ ritonavir-induced hyperlipidemia and reproductive toxicity in male albino rats.

OBJECTIVE: This research work was planned to determine whether Naringin (NG) had any protective effects against lopinavir/ritonavir (LR)-induced alterations in blood lipid levels, hepatotoxicity, and testicular toxicity. MATERIALS AND METHODS: Four groups of six rats each were used for the study: Control (1% ethanol), naringin (80 mg/kg), lopinavir (80 mg/kg)/ritonavir (20 mg/kg), and lopinavir (80 mg/kg)/ritonavir (20 mg/kg) + naringin (80 mg/kg). The drug treatment was continued for 30 days. On the last day, the serum lipid fractions, liver biochemical parameters, testicular antioxidants (enzymatic and non-enzymatic), and the histopathology of the liver and testis tissue were assessed for all rats. RESULTS: Treatment with NG decreased significantly (p<0.05), the baseline serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C), and increased high-density lipoprotein cholesterol (HDL-C). But these parameters were significantly (p<0.05) increased in LR-treated animals. Naringin, co-administered with LR, restored the liver and testicular biochemical, morphological, and histological balance. CONCLUSIONS: This study shows that NG can be used as a treatment for LR-induced biochemical and histological changes in the liver and testes and changes in serum lipid levels.

Levosimendan: mechanistic insight and its diverse future aspects in cardiac care.

Inotropic agents are generally recommended to use in patients with acute decompensated heart failure (HF) with reduced ejection fraction (HFrEF) concurrent to end-organ dysfunction. However, due to certain pharmacological limitations like developing life threatening arrhythmia and tolerance, cannot be employed as much as needed. Meanwhile, Calcium ion (Ca2+) sensitisers exhibits their inotropic action by increasing the sensitivity of the cardiomyocyte to intracellular Ca2+ ion and have been reported as emerging therapeutic alternative in HF cases. Levosimendan (LEVO) is an inodilator and with its unique pharmacology justifying its use in a wide range of cardiac alterations in HF particularly in undergoing cardiac surgery. It is also reported to be better than classical inotropes in maintaining cardiac mechanical efficacy and reducing congestion in acute HF with hypotension. This review paper was designed to compile various evidence about basic pharmacology and potential clinical aspects of LEVO in cardiac surgery and other HF associated alterations. This will benefit directly to the researcher in initiating research and to fill the gaps in the area of thrust.

Trend of recognizing depression symptoms and antidepressants use in newly diagnosed Parkinson's disease: Population-based study.

OBJECTIVES: Although depression symptoms are common among patients with Parkinson's disease (PD), the medical literature still reports underrecognition of depression in patients with PD. Our main objective is to examine the trend of depression recognition during the first year of PD diagnosis using large population data. METHODS: We conducted a population-based study of residents in Wales, using the Secure Anonymized Information Linkage (SAIL) Databank. We included newly diagnosed patients with PD aged 40 years or older with a first PD diagnosis between 2000 and 2015. Depression and antidepressants related data were extracted from SAIL. A series of multilevel logistic regressions were run to determine the factors affecting depression recognition. The results were presented using odds ratios (ORs) with 95% confidence intervals (CI). RESULTS: The study included 6596 patients with PD. About 38% of patients had a recorded code of antidepressants, depression diagnosis, or both within the first year of PD diagnosis. There was a significant association of depression diagnosis, antidepressant use, or both with the year of PD diagnosis (OR 0.972, 95% CI 0.962-0.983). We also found that patients who used monoamine oxidase inhibitors (MAO-B inhibitors) were associated with a lower depression diagnosis, use antidepressants, or both, compared to those who did not use MAO-B inhibitors (OR 0.769, 95% CI 0.627-0.943). CONCLUSION: There is a slight decrease in depression recognition in PD patients between 2000 and 2015, which could be due to an increase in depression recognition during the prodromal phase of PD.

Evaluation of Antibiotic Prescribing Practices and Antimicrobial Sensitivity Patterns in Urinary Tract Related Infectious Diseases in Pediatric Patients.

Complications of urinary tract infections (UTIs) like kidney failure and septicaemia develop once infections spread from the upper urinary tract to other parts of the body by haematogenous dissemination and they pose great health and economic burden to the countries. This retrospective study was conducted among 132 patients with bacterial UTIs in the inpatient department of tertiary care hospital in Abha, Saudi Arabia. During the study period, Escherichia coli (E. coli) and Klebsiella pneumonia (K. pneumonia) along with other 15 different bacteria were isolated. A significant difference (P < 0.05) was observed between the male and female children population in different age groups. We observed fever (84.09%) as a major symptom (P < 0.05), and seizure (9%) was reported as a major concomitant condition among UTI cases. Around 31.82% of E. coli was found to be the most common uropathogens in pediatric cases followed by 25% in K. pneumoniae. E. coli was observed to be more susceptible (92.86%) to amikacin, ceftriaxone, levofloxacin, ertapenem, gentamycin, meropenem, piperacillin-tazobactam, tigecycline, and ceftazidime. However, meropenem, tigecycline, and amikacin were observed to be effective in 100% of cases of K. pneumoniae. Meanwhile, cephalosporins were the most commonly prescribed drug category among different classes of drugs. Almost 99% of pediatric cases, based on their age, were admitted to the ward, and drugs were administered intravenously. We concluded that microbiology laboratory evidence on the causative organisms and choice of treatment together allows tailoring appropriate treatment regimens in conjunction with clinical experiences.

Isolation and characterization of pathogenic Vibrio alginolyticus from sea cage cultured cobia (Rachycentron canadum (Linnaeus 1766)) in India.

Mass mortalities of cobia, Rachycentron canadum, sub-adults occurred during August 2013 in cage culture in the Gulf of Mannar, Mandapam Tamil Nadu, India. The epizootic of disease was started with typical classical clinical signs followed by acute mortality. Grossly, severe haemorrhage and congestion were observed in the gastric mucosa. The abdomen was distended with peritoneal fluid. The heart revealed haemopericardium and fibrinous pericardium. Histologically, the gastric mucosa showed severe erosion and necrosis. Haemorrhagic pericarditis and an increased size of the melano macrophage centre (MMC) in the tail kidney were other histopathological changes. Vibrio sp. was isolated from the gastric lesions and heart blood swab of moribund fishes and it was found to be virulent to the cobia fingerlings. After the challenge, the same bacterium could be re-isolated from moribund fingerlings. The 16S ribosomal RNA of the isolate was amplified and blast analysis of the sequence confirmed that the pathogen was Vibrio alginolyticus. The confirmation was also correlated with its cultural, biochemical and pathomorphological changes. This is the second report and the first incidence of epizootics with severe pathological lesions in cultured cobia in India. The study throws light on the pathology of vibriosis. By practising cage farm management measures, occurrences of infection may be prevented. SIGNIFICANCE AND IMPACT OF THE STUDY: The epizootics of vibriosis caused serious economic losses to farmers. Natural blooms of the pathogen can be prevented by sea cage management measures such as, changing the inner net of the cages, changing the location of the cages to relatively clean water (about 50 m apart) from the affected site and providing shade over the cages while the water temperature rises. Supplementation of the feed with immunostimulants and mineral mixture may be practised to improve the immune response against infection. Early diagnosis and sea cage management measures may prevent occurrences of the infection.

Patient Medication Adherence and Physician Prescribing among Congestive Heart Failure Patients of Yemen.

Congestive heart failure has been associated with high morbidity and mortality requiring hospitalisation and is further complicated by noncompliance and under prescriptions. We aim to determine medication adherence and percentage deviation among Asians population in general and Yemenis in particular. A cross-sectional, prospective observational study with purposive sampling was conducted at two cardiac outpatient centers in 70 congestive heart failure patients for a period of 3 months. An Arabic translated Morisky 4 item scale assessed the adherence of patients. Deviation in prescribing was determined by chart review. All 70 patients had mean age of 56.6±16 years. Morisky 4 item scale predicted low adherence (n=33; 47.1%) and overall nonadherencerate (n=38; 54.2%) was slightly higher than adherence. Percentage nonadherence versus adherence was high with diuretics (53 vs. 46%) and, digoxin (40 vs. 29%). The adherence percentage of angiotensin receptor blockers (9%) and beta blockers (8%) was low. Diuretics were the most prescribed drugs (n=69; 99%), followed by angiotensin converting enzyme inhibitors (n=51; 73%), cardiac glycoside (n=48; 69%), few patients were on angiotensin receptor blockers (n=8; 11%) and (n=9; 13%) beta blockers. The maximum prescribing rate deviation was seen with angiotensin receptor blockers (-89%) and beta blockers (-87%) followed by nitrates (-77%). Digoxin (-31%) and angiotensin converting enzymes (-27%) deviated comparatively less. Prescribing as well as utilisation rates generally were low resulting in nonachievement of therapeutic goals which could be resolved using multimodel approach.

Prevalence and control of cardiovascular risk factors among type 2 diabetes mellitus patients in southern region of Saudi Arabia.

BACKGROUND/AIM: Dyslipidemia is a significant predictor of cardiovascular events and mortality in diabetes patients. The aim of this study is to estimate the prevalence rates, characteristics of dyslipidemia and their control in outpatient population in a Diabetic Centre. METHODS: A cross sectional prospective study design was used to collect data from 255 patients which included patient characteristics, past medical history of CVD, medications and parameters related to DM and cardiovascular risk factor control. Blood pressure and laboratory measurements for glycosylated hemoglobin and lipoprotein panel were recorded. RESULTS: Body mass index (BMI) of the dyslipidemic diabetic patients was significantly higher for females. In terms of age, duration of diabetes, family history, diabetes treatment offered did not differed significantly among genders. Clinical characteristics of HDL values were significantly higher for female in comparison to men (P = 0.02) whereas glycosylated hemoglobin and blood pressure appeared not to differ significantly. Among the three factors studied BMI, duration of diabetes mellitus and drug therapy on lipoprotein levels of diabetes patients, except for the influence of drug therapy which influenced significantly the total cholesterol level (P = 0.02). Number of females with normolipid were more than males (P = 0.009) and number of males with abnormal cholesterol and triglyceride patients were significantly more than females (0.0002). CONCLUSION: Dyslipidemia among males were higher than females which could be a significant risk factor for causing low glycemic control culminating in cardiovascular events. Control of hyperglycaemia and other CVD risk factor appears to be suboptimal in Saudi Arabia. Addressing health system components such as providing medical staff training, incentive to health professionals and better patient education may improve quality of DM care.