Recently, a new formulation containing Mirabegron (MB) and Solifenacin succinate (SFS) has been approved for the management of over active bladder. However, only one analytical method has been reported for the simultaneous determination of both the analytes. Therefore, the current study was design to develop simple UV derivative spectroscopic and rapid RP-HPLC methods for simultaneous determination of MB and SFS. The chromatographic separation of MB and SFS was performed using Phenomenex Kinetex C18 (150mm × 4.5 mm × 5 µm) analytical column. A mixture of Water: Acetonitrile (20:80%v/v) was consider as mobile phase, at a flow rate of 1ml/min and at detector wavelength 225nm. A linear response was observe over the concentration range 2.5-12.5 µg/ml and 0.5-2.5 µg/ml respectively. The first order derivative method was develop by derivatisation of the zero absorption spectra for the first absorption spectra. The Zero crossing point of MB and SFS at 221 nm and 266 nm was obtain respectively. Beer’s law is obey in the concentration range of 7.5-20 µg/ml and 1.5-4 µg/ml for MB and SFS with correlation coefficient (R2) of 0.9984 and 0.9993 respectively. Both the methods were validated in accordance to guidelines for linearity, precision, repeatability, limit of detection (LOD), Limit of Quantification (LOQ), accuracy and robustness. Further, both the methods were validated and compared statistically using Student’s-t-test and employed for the concurrent estimation of MB and SFS in formulations. The proposed methods were simple, accurate, precise, and rapid. Therefore, they can be use for regular quality control of MB and SFS formulations and dissolution studies as well.

Gymnema sylvestre (GS) is a powerful antidiabetic plant that has been utilized in ayurvedic, folk and homeopathic medicine for centuries. In this research, we evaluated the antidiabetic potential of methanolic leaf extract of Gymnema sylvestre. Fractionation was carried out using column chromatography and a total of twenty-eight (28) sub-fractions were obtained which were further screened and pooled into three (3) fractions (A, B and C) by thin layer chromatography based on their retention factor (Rf) values. The fractions were subjected to in vitro a-amylase and a-glucosidase inhibition activity. Some of the compounds identified from LC-MS were subjected to in silico analysis between all the ligands and the receptors with the aid of a docking software. Ligands were imported for visual screening into PyRx software while Biovia Discovery Studio Visualizer was used for protein preparation. Analysis of the properties of drug likeliness of the ligands was done via SwissADME online server according to Lipinski s Rule of Five. Final docking analysis was done through AutoDockVina and Biovia Discovery Studio client 2020. Fraction C showed the best IC50 of 0.84µg/ml a-glucosidase inhibitory activity when compared with fraction A and B, 2.00µg/ml and 1.58µg/ml (a-glucosidase), fraction A produced the best a-amylase activity among the fractions with IC50 of 16.78µg/ml, fraction B with 23.17µg/ml and fraction C with 28.22µg/ml. Molecular docking analysis of the ligands Orcinol (-5.5 kcal/mol) showed strong binding interaction with a-amylase, followed by 3-hydroxy-3-methoxyflavone and Curcumin (-7.1 kcal/mol and -7.6 kcal/mol respectively) compared to acarbose (-8.0 kcal/mol) and Glyinflanin A (-8.4 kcal/mol) interactions. The binding affinity of Orcinol, 3-hydroxy-3-methoxyflavone, Curcumin and Glyinflanin A (-5.7 kcal/mol, -8.0 kcal/mol, -7.6 kcal/mol and -9.1 kcal/mol respectively) were lower compared to acarbose (-9.7 kcal/mol) interaction with a-glucosidase. Thus, compounds identified from Gymnema sylvestre were found to have antidiabetic potentials with Orcinol displaying the most effective binding affinity in potential for drug development.

Diabetes mellitus is a metabolic disease affecting various body organs and systemscausing several complications such ascardiovascular diseases, stroke, nephropathy, retinopathy, neuropathy, erectile dysfunction and diabetic foot ulcer development. Diabetic patients are under oxidative stress and inflammation that play crucial role in complications development.Pomegranate, containingvarious phytochemicals with antioxidant, anti-inflammatory, antihyperglycemic, antihyperlipidemic, antihypertensive, antiatherogenic, antimicrobial, cardioprotective, neuroprotective, regenerative, wound healing andimmuno modulatory bioactivities, at the same time is sufficiently treating diabetesand its’ complications without any side effects as safety tests have shown. Pomegranate treatment improves antioxidant status of the patients, reduces inflammation, ameliorates diabetes improving insulin sensitivity, increasing insulin production and secretion,reducing blood glucose levels, inhibiting hemoglobin glycosylation, protecting pancreas and is contributing to pancreatic islets regeneration and stimulation. It also ameliorates cardiovascular complications decreasing total cholesterol, triglycerides, LDL, lipid peroxidation, atherosclerosis, increasing the beneficial HDL. Pomegranate alsoenhances wound healing byreducing bacterial count, inhibiting quorum sensing and biofilm formation, increasing collagen production, upregulating the EGF, VEGF and TGF-ß1 levelsand leading to excellent epithelialization and neovascularization. Besides, pomegranate treatment ameliorates nephropathy reducing serum creatinine, urine albumin, blood urea nitrogen, urine albumin to creatinine ratio,renal fibrosis, glomerular sclerosis, hypertrophyand interstitial hyperplasia. Pomegranate treatment is preventing or ameliorating neuropathy and alsoimproving erectile function by increasingintracavernosal blood flow and MICP/MAP percentage in patients with atherosclerosis. Moreover, pomegranate ameliorates retinopathy reducing the oxidative stress biomarker 8-OHdG, decreasing the levels of sialic acid, malondialdehyde, improving retina cell layers and delaying cataract onset. Is important to be mentioned that while in diabetic individuals the values of several biochemical parameters were significantly improved, at the same time there were not changes on thehealthy individuals’ biochemical parameters which were normal, indicatingexcept its’ excellent pharmaceutical properties alsoa regulatory role of pomegranate as it is acting only whenever it is needed for health achievement and maintenance.These results indicate that pomegranate can offer an alternative,safe, holistic treatment for diabetes and its’ complications, improving the general health and quality of life of the patient.

Background/Objectives: Musa paradisiaca (Plantain) is used as a traditional therapeutic medicinal plant employed in various diseases. This study was carried out to evaluate the nutraceutical potentials of the ripe and unripe peels of Musa paradisiaca. The phytochemical screening as well as antimicrobial activity of various extracts (methanol and ethanol) of ripe and unripe peels of Musa paradisiaca was also evaluated. Methods: Proximate and mineral analyses of the samples were performed as per the standard methods of the Association of Official Analytical Chemists. Preliminary phytochemical screening of methanol and ethanol extracts of the peels was also carried out in accordance with standard methods. The antimicrobial activities of methanol and ethanol extracts of M. paradisiaca peel were tested in-vitro against isolates of clinical origin by agar well diffusion method. Results: Phytochemical analysis of both peel extracts indicated the presence of flavonoids, terpenoids, starch, steroids, and reducing sugars. The mineral analysis indicated the presence of essential minerals such as iron, zinc, copper and manganese. The fat, protein, crude fibre and carbohydrate composition values of the unripe peel extract were found higher than the ripe samples. The ethanol and methanol extracts of both the ripe and unripe peels of M. paradisiaca used at various concentrations showed no antibacterial activities against the organisms. Conclusion: This study concludes that ripe and unripe plantain fruit peels thought to be of little or no significance could serve as nutraceuticals and a medicinally vital material in animal health and probably humans.

Drug-induced nephrotoxicity is increasingly recognized as a significant contributor to acute kidney injury and chronic kidney disease. Acute kidney injury is a very common diagnosis, present in up to 60% of critical patients, and its third main cause is drug toxicity. Systematic and quantitative studies of nephrotoxicity have become increasingly important due to rising concerns of drug induced nephrotoxicity. Drugs frequently interact with more than one target, with hundreds of these targets linked to the side effects of clinically used therapeutics. This is based on the hypothesize that drugs with same side effects are likely to have similar targets (Zhang et al., 2017). Developing a computational model to predict drug induced nephrotoxicity will provide a screening tool for nephrotoxicity thereby minimizing the number of nephrotoxic drugs released to the market. The study was aimed at exploring the various molecular and structural mechanisms for drug induced nephrotoxicity using computer simulation techniques; pharmacophore studies, PASSONLINE target identification and molecular docking simulation techniques. Hydrogen bond donor and hydrogen bond acceptor were the features common to nephrotoxic drugs, kidney injury molecule 1, neutrophil gelatinase associated lipocalin and type IV collagen were the common nephrotoxic targets. The nephrotoxic drugs demonstrated excellent binding affinities against the common targets and superimpose with each other and the co-crystalized ligand in the active pocket of each of the targets. These findings imply that nephrotoxic drugs potentiate the effects of these targets and might be molecular mechanism responsible for the nephrotoxicity associated with drugs.

The prevalence of periodontitis is still quite high, which is about 74.1%. Periodontitis therapy is currently a combination of root debridement and antibiotica is still not satisfactory, especially for severe periodontitis and systemic diseases. Golden sea cucumber is a natural ingredient of marine life containing proteins and active ingredients that function as antibacterial, anti-inflammatory and antioxidant. The goal in this study was to test the formulation and physical stability of the gold sea cucumber extract gel preparation (Sticopus Hermanii) as an anti-periodontitis using variations in gel base concentrations. Gold sea cucumber extract gel with HPMC is tested formulation, stability, pH and viscosity. Stability test at weeks 0, 2, 4, 6, 8 checked for changes in consistency, color, odor stability testing using climatic chamber pH test using pH meter. Viscosity test is performed in Week 1. Measurements by using LVDV-E type Brookfiled viscometers with spindles The best stability test is obtained on formulas with HPMC 5%, the highest pH obtained on formulas with a CMC base of 3% and obtained at the measurement of the 8th week is 8. The results of the optimasi test resulted in a concentration of 5% HPMC that met organoleptic, pH, stability and viscosity tests.

Background: Spasticity has been proven to affect the quality of life and functional rehabilitation in patients post-stroke. Several studies aimed to investigate ways to reduce muscle tonicity in this population. Peripheral joint mobilization (PJM) as well as cryotherapy can be used effectively to reduce spasticity and enhance the range of motion. Objectives: This study aimed to investigate the direct effect of cryotherapy, and that of peripheral joint mobilization, on spasticity as a primary outcome and range of motion as a secondary outcome in stroke patients. Methods: Eighteen participants met the inclusion criteria. Patients with ankle plantarflexor spasticity (n=14), patients with biceps brachii spasticity (n=13), and patients with triceps brachii spasticity (n=10) underwent our interventions on two distinct visits. On the first session, Kaltenborn’s PJM was performed, while on the second session ice-massaging technique was applied on the biceps brachii, triceps brachii, and gastrocnemius muscles over the duration of five continuous minutes. The assessment tools used were Modified ashworth scale (MAS) to assess spasticity level and goniometer to evaluate the range of motion (ROM). Statistical tests were performed using SPSS software, Version 23.0. Results: Cryotherapy and peripheral joint mobilization showed a significant reduction in spasticity of the biceps brachii and triceps brachii muscles (p < 0.05), while only cryotherapy had a significant change on gastrocnemius muscle. For ROM, only PJM showed a significant positive change on both active and passive ranges. Conclusion: Both modalities showed effectiveness in direct reduction of spasticity, hence contributing to a more manageable and practical functional rehabilitation of stroke patients

Liver is a vital organ in the body and works to filter blood from the digestive tract before passing it on to the rest of the body. Liver diseases are varied and may be assessed by liver function tests including ALT. The main objectives of this study were to use neural network analysis to predict liver disease, and to identify the relative contribution of liver disease predictors. A dataset of Indian liver patients posted on Kaggle was used to be analyzed for liver disease prediction. The dataset included 583 subjects among whom 71.4% had liver disease. Study predictors included age, gender, ALT, AST, bilirubin, albumin, total protein, albumin globulin ratio, and alkaline phosphatase. The prediction model was effective in 79.6% predicting the liver disease. The most important predictor was ALT, and the least important predictor was alkaline phosphatase. Taken together, using neural network analysis is effective in predicting liver disease from one side and from another side, it can be improved to give more accurate results.

Background: Patients with chronic hepatitis have impaired glucose metabolism with hyperinsulinemia and insulin resistance, this hyperinsulinemia has been shown to be due to decreased insulin catabolism rather than increased pancreatic insulin secretion. We aimed to evaluate insulin resistance in non-diabetic patients with chronic hepatitis C virus infection. Subjects and methods: The study was a case-control study conducted in Tropical Medicine and Gastroenterology Department King Abdullah University Hospital. 60 patients and 30 healthy controls were included in the study. The patients were classified into two groups: Group A: 30 patients with chronic hepatitis C infection were selected with positive HCV RNA in serum for at least 6 months; Patients were not receiving anti-viral therapy at the time of sampling. They showed no evidence of cirrhosis. Group B: 30 patients with HCV related liver cirrhosis. They were divided according to Child Pugh score; twenty patients with HCV related compensated liver cirrhosis (Child A). Ten patients with HCV related decompensated liver cirrhosis (Child B and C). Group C: The control group: included 30 healthy individuals. All patients and controls were subjected to the following: Liver function tests: Alanine transaminase (ALT), Aspartate transaminase (AST), total and direct bilirubin, total protein, serum albumin. Prothrombin time (PT) & international normalization ratio (INR). Renal function tests: Blood urea nitrogen (BUN), Na, K. Complete blood count. Alpha fetoprotein (aFP). Diagnosis of chronic hepatitis C infection was based on positive HCV by PCR, persistent elevation of liver enzymes more than 6 months and liver biopsy for some of the patients. Anti-hepatitis C virus antibody (HCV Ab) using third generation enzyme linked immune sorbant assay (ELISA) test., Hepatitis B virus (HBV): HBVsAg., Overnight fasting and two hours postprandial blood glucose level. Fasting serum insulin of everyone. Insulin resistance was determined via the Homeostasis Model assessment (HOMA-IR) by the following equation: - Insulin resistance: Fasting insulin (µu/ml) x Fasting glucose (mmol/L) 22.5 An index value of > 2.5 was defined as IR. This cutoff value was chosen because studies suggested that a HOMA-IR of 2.4-3.0 is probably suitable to define IR in CHC patients. Blood samples were collected after 12 hours of overnight fasting. Results: We found that out of 30 CHC and 30 LC (20 compensated LC, 10 de compensated LC) 8 (26.7%); 8 (40%) patients and 5(50%) respectively had HOMA-IR levels greater than 2.5, which is consistent with IR diagnosis. Decompensated cirrhotic patients showed higher frequency of IR compared to CHC and compensated cirrhotic patients. Conclusion: In chronic hepatitis C patients, HOMA-IR, fasting serum insulin and fasting blood glucose were significantly higher than healthy controls (p <0.0001).

Liver is a vital organ in the body that perform very important functions to keep health hemostasis. Liver function tests are a group of tests that determine the liver health in physiological and pathological conditions. The main objectives of the present study were to assess liver function using a panel of liver function tests among a sample of liver patients and to compare their levels with a sample of subjects who had no liver disease. To achieve the study objectives, we analyzed a dataset posted on Kaggle. The dataset described Indian liver patients and included 583 subjects among which 414 patients with liver disease and 167 subjects without liver disease. The results showed that demographic variables including age and gender were predictors of liver disease. On the other hand, liver function tests including bilirubin, ALT, AST, albumin, albumin globulin ratio, alkaline phosphatase were significantly associated with liver disease. The level of total proteins was not significantly associated with liver disease. Taken together, liver function tests can be used to assess liver disease. The interpretation of total proteins and AST should be considered with cautious