Dual-Use Vaccine for Diarrhoeal Diseases: Cross-Protective Immunogenicity of a Cold-Chain-Free, Live-Attenuated, Oral Cholera Vaccine against Enterotoxigenic Escherichia coli (ETEC) Challenge in BALB/c Mice.

In low- and middle-income countries, diarrhoeal diseases are the second most common cause of mortality in children, mainly caused by enterotoxin-producing bacteria, such as Shigella, Vibrio, Salmonella, and Escherichia coli. Cholera and traveller's diarrhoea are caused by Vibrio cholerae (O1 and O139 serogroups) and enterotoxigenic Escherichia coli (ETEC), respectively. The cholera toxin (CT) produced by V. cholerae and the heat-labile enterotoxin (LT) of ETEC are closely related by structure, function, and the immunological response to them. There is no exclusive vaccine for ETEC; however, cholera vaccines based on the CT-B component elicit a short-term cross-protection against ETEC infection. In this context, the cross-protective efficacy of MyCholTM, a prototype cold-chain-free, live-attenuated, oral cholera vaccine against V. cholerae O139 was evaluated in BALB/c mice. The 100% lethal dose (LD100) of 109 CFU/mL of the ETEC H10407 strain was used for the challenge studies. The mice immunised with MyChol™ survived the challenge by producing anti-CT antibodies, which cross-neutralised the LT toxin with no body weight loss and no sign of diarrhoea. Compared to unimmunised mice, the immunised mice elicited the neutralising antitoxin that markedly decreased ETEC colonisation and fluid accumulation caused by ETEC H10407 in the intestines. The immunised mice recorded higher antibody titres, including anti-CT IgG, anti-LT IgG, anti-CT-B IgG, and anti-LTB IgG. Only a two-fold rise in anti-CT/CT-B/LT/LT-B IgA was recorded in serum samples from immunised mice. No bactericidal antibodies against ETEC H10407 were detected. This investigation demonstrates the safety, immunogenicity, and cross-protective efficacy of MyCholTM against the ETEC H10407 challenge in BALB/c mice.

Caloric Vestibular Stimulation Induced Enhancement of Behavior and Neurotrophic Factors in Chronic Mild Stress Induced Rats.

Background: Caloric Vestibular Stimulation (CVS) is a non-invasive technique for stimulating the vestibular system. The vestibular system maintains equilibrium and acts as a moderator of mood, emotional control, and stress levels. Stress is a disruption of psychological, behavioral, and physiological homeostasis that affects people of all ages in today's world. Thus, modest therapeutic procedures like vestibular stimulation can be practiced to effectively reduce stress. Hence, the purpose of the study was to determine the effect of vestibular stimulation on improving behavioral alterations and neurotrophic factors in rats exposed to Chronic Mild Stress (CMS). Methodology: The study employed 24 healthy male Sprague Dawley rats divided into four groups (n = 6). CMS was induced for 28 days with a variety of stimuli. Bilateral CVS with hot water (temperature ≈40°C) was started on Day 14 of CMS and continued for 15 days. On days 1, 15, and 28, locomotor activity (LA), wire grip strength (WGS), fall off time (FT), and immobilization time (IT) were measured, and the data were analyzed statistically. Additionally, neurotrophic factors such as Brain Derived Neurotrophic Factor (BDNF) and Glial cell line-Derived Neurotrophic Factor (GDNF) were observed in rats' hippocampus. Results: On days 15 and 28, the CMS-induced group showed a significant reduction in LA, WGS, FT and IT in comparison to the control group. On day 28, the CVS-induced group demonstrated a significant increase in WGS, FT and IT when compared to the CMS group. Immunohistochemical analysis revealed that animals subjected to CMS had decreased BDNF and GDNF expression compared to the control group, indicating neuronal dysfunction in the hippocampus in response to stress. However, therapy with CVS increased BDNF and GDNF expression, thereby regenerating damaged hippocampus nerve terminals. Conclusion: The findings of the current study revealed that CVS is a safe and simple neuroprotective treatment against stress and a promising non-invasive technique for overcoming the motor symptoms associated with it. The findings may pave the way for future research and therapeutic applications of CVS for stress management.

Live, Genetically Attenuated, Cold-Chain-Free Cholera Vaccine-A Research and Development Journey: Light at the End of a Long Tunnel.

Cholera, a diarrheal disease caused by Vibrio cholerae (V. cholerae) O139 and O1 strains, remains a public health problem. The existing World Health Organization (WHO)-licenced, killed, multiple-dose oral cholera vaccines demand 'cold-chain supply' at 2 °C-8 °C. Therefore, a live, single-dose, cold-chain-free vaccine would relieve significant bottlenecks and costs of cholera vaccination campaigns. Our cholera vaccine development journey started in 2000 at Universiti Sains Malaysia with isolation of the hemA gene from V. cholerae, followed by development of a gene mutant vaccine candidate VCUSM2 against V. cholerae O139 in 2006. In 2010, VCUSM2 reactogenicity was reduced by replacing its two wild-type ctxA gene copies with mutated ctxA to produce strain VCUSM14. Introducing the hemA gene into VCUSM14 created VCUSM14P, a strain with the 5-aminolaevulinic acid (ALA) prototrophic trait and excellent colonisation and immunological properties (100% protection to wild-type challenged rabbits). It was further refined in Asian Institute of Medicine, Science and Technology (AIMST University), with completion of single- and repeated-dose toxicity evaluations in 2019 in Sprague Dawley (SD) rats, followed by development of a novel cold-chain-free VCUSM14P formulation in 2020. VCUSM14P is unique for its intact cholera toxin B, a known mucosal adjuvant. The built-in adjuvant makes VCUSM14P an ideal vaccine delivery platform for emerging diseases (e.g. severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] and tuberculosis). Our vaccine formulation mimics natural infection, remains non-reactogenic and immunogenic in vivo, and protects against infection and disease. It will also cost less and be less cumbersome to distribute due to its stability at room temperature. These features could revolutionise the outreach of this and other vaccines to meet global immunisation programmes, particularly in low-resourced areas. The next stage of our journey will be meeting the requisite regulatory requirements to produce the vaccine for rollout to countries where it is most needed.

Antidiabetic and Antihyperlipidemic Effects of Methanolic Extract of Leaves of Spondias mombin in Streptozotocin-Induced Diabetic Rats.

Objective: Spondias mombin is a plant that reported to have anticonvulsant, antimicrobial, antioxidant, antiulcer, antiasthmatic, and wound healing activities. Diabetes dyslipidemic effect of Spondias mombin leaves is not clear. Hence, current study planned to evaluate the antidiabetic and antihyperlipidemic effects of methanolic extract of leaves of Spondias mombin (MESM) in streptozotocin (STZ) induced diabetic rats. Methods: Phytochemicals were determined by standard method and antioxidant activity was determined by DPPH free radical scavenging and FRAP assay. Diabetes was induced by injecting a single dose of STZ (55 mg/kg) into female sprague dawley rats. After 3 days of induction of diabetes, the diabetic animals were treated for 28 days with MESM (125, 250, and 500 mg/kg) and glibenclamide (20 mg/kg) orally. The body weight of rats and blood glucose levels were monitored at regular intervals during the experiment. At the end of study, blood sample was collected from all the animals and subjected to biochemical, lipid profile, and they were sacrificed and their organs such as pancreas, liver and kidney were used for histopathological analysis. Results: Quantitative analysis of MESM showed the presence of anthraquinone, tannins, saponins, steroid, phenols, flavonoids, alkaloids, and reducing sugars. Reduction in body weight and elevated blood glucose were observed in diabetic rats. Treatment with MESM in a concentration of 125, 250, and 500 mg/kg significantly reversed the elevated levels of blood glucose, reduced aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, urea, creatinine, total serum cholesterol (TC), serum triglyceride (TG), low-density lipoprotein (LDL), Very low-density lipoprotein (VLDL), and increased plasma insulin, total protein, albumin, globulin, A/G ratio, and high-density lipoprotein (HDL). Conclusion: MESM exhibited a significant antidiabetic and antihyperlipidemic activities against STZ-induced diabetes in rats.

Exploring Antimicrobials from the Flora and Fauna of Marine: Opportunities and Limitations.

About 95% of earth living space lies deep below the ocean's surface and it harbors extraordinary diversity of marine organisms. Marine biodiversity is an exceptional reservoir of natural products, bioactive compounds, nutraceuticals and other potential compounds of commercial value. Timeline for the development of the drug from a plant, synthetic and other alternative sources is too lengthy. Exploration of the marine environment for potential bioactive compounds has gained focus and huge opportunity lies ahead for the exploration of such vast resources in the ocean. Further, the evolution of superbugs with increasing resistance to the currently available drugs is alarming and it needs coordinated efforts to resolve them. World Health Organization recommends the need and necessity to develop effective bioactive compounds to combat problems associated with antimicrobial resistance. Based on these factors, it is imperative to shift the focus towards the marine environment for potential bioactive compounds that could be utilized to tackle antimicrobial resistance. Current research trends also indicate the huge strides in research involving marine environment for drug discovery. The objective of this review article is to provide an overview of marine resources, recently reported research from marine resources, challenges, future research prospects in the marine environment.

Repeated dose toxicity evaluation of a cold chain-free, live, attenuated oral cholera vaccine in Sprague Dawley rats.

The repeated dose toxicity of a prototype cold chain-free, live, attenuated oral cholera vaccine containing 5 × 106 CFU/mL of the VCUSM14P strain was evaluated in Sprague Dawley (SD) rats (single dose administered daily for 30 days) to ascertain its safety for clinical use. Repeated dose toxicity studies for cholera vaccines in the literature have administered 2 or 3 fixed doses at 7, 14, 21 or 69 day intervals. The present study reports an evaluation of 30 repeated doses of cholera vaccine administered at three different concentrations (Group II (1.25 × 106 CFU), Group III (2.5 × 106 CFU) and Group IV (5 × 106 CFU)) in SD rats. The liquid vaccine was administered orally to the rats with the respective dose every day, and normal saline was administered to the control group (Group I). No significant difference (P > 0.05) was observed in the body weights and biochemical parameters of the rats after 15 and 30 repeated doses compared to those of the control group. However, compared to those of Group I, a significant increase (P < 0.05) in the organ to body weight ratios of the lungs, ureter, liver, kidney, heart and spleen was found in G-II, G-III and G-IV. In the haematological analysis, a significant increase in the WBC was observed in G-II and G-IV compared to that in G-I. The histopathological findings indicated mild to moderate degeneration in the liver, kidney, heart and spleen in the treated rats. Mild to moderate lymphocytic infiltration in the lungs was observed in the G-II and G-III rats, and severe infiltration was observed in the G-IV rats. These histopathological findings may be attributed to the 30 doses of vaccine given in daily succession without an interval. In the acute toxicity study, a single dose of vaccine up to 10 × 106 CFU did not cause any adverse effects and lethality in SD rats.

Smartphone usage and increased risk of mobile phone addiction: A concurrent study.

OBJECTIVE: This study aimed to study the mobile phone addiction behavior and awareness on electromagnetic radiation (EMR) among a sample of Malaysian population. METHODS: This online study was conducted between December 2015 and 2016. The study instrument comprised eight segments, namely, informed consent form, demographic details, habituation, mobile phone fact and EMR details, mobile phone awareness education, psychomotor (anxious behavior) analysis, and health issues. Frequency of the data was calculated and summarized in the results. RESULTS: Totally, 409 respondents participated in the study. The mean age of the study participants was 22.88 (standard error = 0.24) years. Most of the study participants developed dependency with smartphone usage and had awareness (level 6) on EMR. No significant changes were found on mobile phone addiction behavior between the participants having accommodation on home and hostel. CONCLUSION: The study participants were aware about mobile phone/radiation hazards and many of them were extremely dependent on smartphones. One-fourth of the study population were found having feeling of wrist and hand pain because of smartphone use which may lead to further physiological and physiological complication.

Ameliorative Effect of Curcumin on Olanzapine-induced Obesity in Sprague-Dawley Rats.

OBJECTIVE: To evaluate the effect of curcumin on olanzapine-induced obesity in rats. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were used for experiments. The animals were divided into six groups, namely, normal control, olanzapine control, betahistine (10 mg/kg), and curcumin 50, 100, and 200 mg/kg treated groups. Except the normal control group, all other animals were administered with olanzapine 4 mg/kg intraperitoneally to induce obesity. The drugs were administered once daily, per oral for 28 days. During the experiment, body weight changes and behavior alterations were monitored at regular intervals. At the end of the experiment, blood sample was collected from all the experimental animals for biochemical analysis. Part of the liver and kidney tissues was harvested from the sacrificed animals and preserved in neutral formalin for histopathological studies. RESULTS: Curcumin showed a significant reduction in olanzapine-induced body weight gain on the rats and improved the locomotor effects. The effect of curcumin on olanzapine-induced body weight gain is not comparable with that of betahistine. CONCLUSION: This study has shown metabolic alteration effect of curcumin on olanzapine, an antipsychotic drug, treated SD rats. SUMMARY: Olanzapine is an atypical antipsychotic drug used for the treatment of schizophrenia and bipolar disorder. Obesity is an adverse effect of olanzapine, and the present study was made an attempt to study the effect of curcumin on olanzapine-induced obesity in rats. In this present study, curcumin significantly reduced olanzapine-induced body weight gain in rats. Abbreviations Used: 5HT: 5-hydroxytryptamine, ALP: Alkaline phosphatase, ALT: Alanine transaminase, ANOVA: Analysis of variance, AST: Aspartate transaminase, CMC: Carboxymethyl cellulose, D: Dopamine, H and E: Hematoxylin and Eosin stain, H: Histamine, HDL-C: Highdensity lipoprotein cholesterol, IP: Intraperitoneal, MAO: Monoamine oxidase, NaOH: Sodium hydroxide, SD rats: Sprague Dawley rats, TCs: Total cholesterols, TG: Triglyceride.

Curcumin: the spicy modulator of breast carcinogenesis.

Worldwide breast cancer is the most common cancer in women. For many years clinicians and the researchers are examining and exploring various therapeutic modalities for breast cancer. Yet the disease has remained unconquered and the quest for cure is still going on. Present-day strategy of breast cancer therapy and prevention is either combination of a number of drugs or a drug that modulates multiple targets. In this regard natural products are now becoming significant options. Curcumin exemplifies a promising natural anticancer agent for this purpose. This review primarily underscores the modulatory effect of curcumin on the cancer hallmarks. The focus is its anticancer effect in the complex pathways of breast carcinogenesis. Curcumin modulates breast carcinogenesis through its effect on cell cycle and proliferation, apoptosis, senescence, cancer spread and angiogenesis. Largely the NFkB, PI3K/Akt/mTOR, MAPK and JAK/STAT are the key signaling pathways involved. The review also highlights the curcumin mediated modulation of tumor microenvironment, cancer immunity, breast cancer stem cells and cancer related miRNAs. Using curcumin as a therapeutic and preventive agent in breast cancer is perplexed by its diverse biological activity, much of which remains inexplicable. The information reviewed here should point toward potential scope of future curcumin research in breast cancer.

Acute and subchronic toxicity studies of methanol extract of Polygonum minus leaves in Sprague Dawley rats.

Medicinal plant preparations may contain high levels of toxic chemical constituents to potentially cause serious harm to animals and/or humans. Thus, toxicity studies are important to assess the toxic effects of plant derived products. Polygonum minus is used traditionally for different ailments in Southeast Asia. This study was conducted to establish the acute and subchronic toxicity profile of the methanol extract of P. minus leaves. The acute toxicity study showed that the methanol extract of P. minus is safe even at the highest dose tested of 2000 mg/kg in female Sprague Dawley rats. There were no behavioural or physiological changes and gross pathological abnormalities observed. The subchronic toxicity study of methanol extract of P. minus at 250, 500, 1000 and 2000 mg/kg were conducted in both sexes of Sprague Dawley rats. There were no changes observed in the extract treated animal's body weight, food and water intake, motor coordination, behaviour and mental alertness. The values of haematological and biochemical parameters were not different between the treated and control animals. The relative organ weights of extract-treated animals did not differ with that of control animals. Based on the present findings, the methanol extract of P. minus leaves could be considered safe up to the dose of 2000 mg/kg.

Acyclovir-Polyethylene Glycol 6000 Binary Dispersions: Mechanistic Insights.

The dissolution and subsequent oral bioavailability of acyclovir (ACY) is limited by its poor aqueous solubility. An attempt has been made in this work to provide mechanistic insights into the solubility enhancement and dissolution of ACY by using the water-soluble carrier polyethylene glycol 6000 (PEG6000). Solid dispersions with varying ratios of the drug (ACY) and carrier (PEG6000) were prepared and evaluated by phase solubility, in vitro release studies, kinetic analysis, in situ perfusion, and in vitro permeation studies. Solid state characterization was done by powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) analysis, and surface morphology was assessed by polarizing microscopic image analysis, scanning electron microscopy, atomic force microscopy, and nuclear magnetic resonance analysis. Thermodynamic parameters indicated the solubilization effect of the carrier. The aqueous solubility and dissolution of ACY was found to be higher in all samples. The findings of XRD, DSC, FTIR and NMR analysis confirmed the formation of solid solution, crystallinity reduction, and the absence of interaction between the drug and carrier. SEM and AFM analysis reports ratified the particle size reduction and change in the surface morphology in samples. The permeation coefficient and amount of ACY diffused were higher in samples in comparison to pure ACY. Stability was found to be higher in dispersions. The results suggest that the study findings provided clear mechanical insights into the solubility and dissolution enhancement of ACY in PEG6000, and such findings could lay the platform for resolving the poor aqueous solubility issues in formulation development.

Influence of Extracting Solvent on Pharmacological Activity and Cytotoxicity of Polygonum minus, a Commonly Consumed Herb in Southeast Asia.

OBJECTIVE: To investigate the antihyperlipidemic, antioxidant, and cytotoxic effect of aqueous and methanol extract of leaves of Polygonum minus. MATERIALS AND METHODS: Acute antihyperlipidemic effect was studied on chemically induced hyperlipidemic rat model. Treated groups received aqueous and methanol extract of leaves of P. minus respectively (1000 mg/kg; oral) whereas standard treated group received atorvastatin (60 mg/kg; oral) for 3 consecutive days. Blood samples were collected at fixed intervals for lipid profile analysis. Antioxidant effects were studied using 1,1-diphenyl-2-picrylhydrazyl, 2,2-azinobis 3-ethylbenzothiazoline 6-sulfonate, and ferric reducing antioxidant power assays. The total flavonoids content and total phenolic contents were also estimated. Cytotoxicity of both extracts was studied on one normal and three cancer cell lines using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay method. RESULTS: The methanol extract showed significant reduction in total cholesterol (P < 0.001), triglycerides (P < 0.01), LDL (P < 0.05), VLDL (P < 0.01), atherogenic index (P < 0.001), and elevation of HDL (P < 0.05) levels than the aqueous extract. Similarly, the antioxidant investigations also demonstrated that the methanol extract had higher antioxidant capacity than aqueous extract. Both extracts were not toxic to normal (EA.hy926) as well as to cancer (HCT116, HT29, and HeLa) cells. Significant correlation was demonstrated between total phenolic and total flavonoids contents with the antioxidant activity but not with the antihyperlipidemic effect, suggesting other groups of chemical constituents may be mainly responsible for the antihyperlipidemic effect of this plant. CONCLUSION: The study demonstrated that the presence and extent of bioactivities are influenced by solvents used for extraction. This study confirmed the antihyperlipidemic effect of leaves of P. minus in acute hyperlipidemic rat model. SUMMARY: Polygonum minus is an herbaceous flowering plant.This plant possess high amount of phenolics and flavonoidsThis study focused on the antioxidant, cytotoxicity and antihyperlipidemic effect of aqueous and methanol extracts of leaves of P. minusThe extracts possess significant antioxidant activity and antihyperlipidemic activity but they are not toxic to normal and cancer cells tested.The antioxidant activity is well correlated with phenolic and flavonoids contents but the antihyperlipidemic activity is not correlated with antioxidant effect. Abbreviations used: CVDs: Cardiovascular diseases, LDL: Low-density lipoprotein, DDPH: 1,1-Diphenyl-2-picrylhydrazyl radical, TPTZ: 2,4,6,-tris(1-pyridyl)-5-triazine, ABTS: 2,2'-Azino-di-[3-ethylbenzthiazoline Sulfonate], HDL: High-density lipoprotein, VLDL: Very low-density lipoprotein, TC: Total cholesterol, TG: Triglycerides, EC50: Half maximal effective concentration, LD50: Median lethal dose.

Evaluation of in vivo antitumor activity of cleistanthin B in Swiss albino mice.

To evaluate the in vivo antitumor activity of cleistanthin B in Ehrlich's ascites carcinoma (EAC) and Dalton's ascites lymphoma (DAL) cell lines induced malignant ascites mouse models and DAL cell line induced solid tumor mouse model. All animals were injected with 2 × 106 EAC/DAL cells i.p./s.c. to induce malignant ascites and solid tumor and treated with 5-fluorouracil (5-FU) 20 mg/kg or cleistanthin B for 10 days. Cleistanthin B was given at three doses viz. 25, 50 and 100 mg/kg. The percentage increase in life span and the overall survival in malignant ascites animals and the tumor volume in solid tumor animals were measured. The haematological parameters were assessed in all animals before and 2 weeks after the treatment. Cleistanthin B 50 mg/kg and 5-FU significantly prolonged the life span (>25%) of malignant ascites tumor bearing animals. The overall survival was significantly improved by both. Only cleistanthin B 50 mg/kg significantly reduced the elevated WBC counts in EAC tumor bearing animals. Both 5-FU and cleistanthin B 50 mg/kg reversed the malignancy induced increase in neutrophils and platelet counts and decrease in lymphocyte counts but not to the normal range. Only 5-FU significantly reduced the solid tumor volume. None of the three doses of cleistanthin B was effective against the solid tumor. Cleistanthin B has antitumor activity against EAC and DAL tumor mice but it is not as effective as 5-FU. At 50 mg/kg dose cleistanthin B exerts significant antitumor activity compared to 25 and 100 mg/kg dose. Its effect on WBC count is higher and advantageous when compared to 5-FU. But cleistanthin B in the doses used is not effective against solid tumor.

Overviews of Biological Importance of Quercetin: A Bioactive Flavonoid.

Antioxidants are substances that may protect cells from the damage caused by unstable molecules such as free radicals. Flavonoids are phenolic substances widely found in fruits and vegetables. The previous studies showed that the ingestion of flavonoids reduces the risk of cardiovascular diseases, metabolic disorders, and certain types of cancer. These effects are due to the physiological activity of flavonoids in the reduction of oxidative stress, inhibiting low-density lipoproteins oxidation and platelet aggregation, and acting as vasodilators in blood vessels. Free radicals are constantly generated resulting in extensive damage to tissues leading to various disease conditions such as cancer, Alzheimer's, renal diseases, cardiac abnormalities, etc., Medicinal plants with antioxidant properties play a vital functions in exhibiting beneficial effects and employed as an alternative source of medicine to mitigate the disease associated with oxidative stress. Flavonoids have existed over one billion years and possess wide spectrum of biological activities that might be able to influence processes which are dysregulated in a disease. Quercetin, a plant pigment is a potent antioxidant flavonoid and more specifically a flavonol, found mostly in onions, grapes, berries, cherries, broccoli, and citrus fruits. It is a versatile antioxidant known to possess protective abilities against tissue injury induced by various drug toxicities.

Hypertension influences the exponential progression of inflammation and oxidative stress in streptozotocin-induced diabetic kidney.

OBJECTIVE: To investigate the association of hypertension coexisting with diabetes mellitus with oxidative stress and inflammation in the kidneys of streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: Male Wistar rats were used for the experiments. Blood glucose (BG), urea, blood pressure (BP), and heart rate (HR) were analyzed before and 48 h after STZ injection. Further, these parameters were monitored up to 3 months of diabetes induction. Subsequently, the inflammatory markers (C-reactive protein, tumor necrosis factor-alpha, and nitrate) and oxidative stress markers were estimated after 3 months of diabetes induction in the kidney homogenate. Histological analysis of renal tissue was also carried out. RESULTS: Linear elevation of BG, urea, mean arterial pressure (MAP), and HR was observed up to 3 months of diabetes induction. In the same manner, inflammatory and oxidative stress markers were also found to be significantly increased. Notably, the histological analysis revealed the signs of nephropathy such as increased mesangial cell number, thickness of basement membrane, and renal artery. Inflammatory and oxidative stress markers positively correlated with elevated BP and BG, but the correlation was better with BP rather than BG. CONCLUSION: Hypertension has a strong implication in the increased oxidative stress and inflammation of diabetic kidney at the very early stage of diabetes mellitus.

Mechanistic insights into acyclovir-polyethylene glycol 20000 binary dispersions.

OBJECTIVE: The objective of this study is to provide a mechanistic insight into solubility enhancement and dissolution of acyclovir (ACY) by polyethylene glycol20000 (PEG20000). MATERIALS AND METHODS: Solid dispersions with differing ratios of drug (ACY) and carrier (PEG20000) were prepared and evaluated by phase solubility, in vitro release studies, kinetic analysis, in situ perfusion, and in vitro permeation studies. Solid state characterization was also done by Powder X-Ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared spectroscopy (FT-IR) analysis and surface morphology was assessed by Polarizing Microscopic Image (PMI) analysis, Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), and Nuclear Magnetic Resonance (NMR) analysis. RESULTS: Thermodynamic parameters proved the solubilization effect of carrier. The aqueous solubility and dissolution of ACY were increased in all samples. Formation of solid solution, crystallinity reduction, and absence of interaction between drug and carrier was proved by XRD, DSC, and FTIR analysis. The particle size reduction and change in surface morphology were confirmed by SEM and AFM and analysis. The permeation coefficient and amount of drug diffused was higher in samples as compared to ACY. The stability was high in dispersions, and it was proved by NMR analysis. CONCLUSION: The mechanical insights into the enhancement of solubility and dissolution could be used as a platform to improve the aqueous solubility for other poor water soluble drugs.

Evaluation of Antidiabetic and Antihyperlipidemic Effects of Hydroalcoholic Extract of Leaves of Ocimum tenuiflorum (Lamiaceae) and Prediction of Biological Activity of its Phytoconstituents.

OBJECTIVE: The aim was to evaluate the anti-diabetic and anti-hyperlipidemic effects of hydroalcoholic extract of leaves of Ocimum tenuiflorum (Lamiaceae) and prediction of biological activities of its phytoconstituents using in vivo anti-diabetic model and in silico analysis respectively. MATERIALS AND METHODS: The leaves of O. tenuiflorum were extracted with 60% ethanol, and the extract was used for further pharmacological screening. The acute toxicity of the extract was evaluated as per the guidelines set by the Organization for Economic Co-operation and Development, revised draft guidelines 423. The oral anti-diabetic activity of the hydroalcoholic extract of O. tenuiflorum (125, 250 and 500 mg/kg) was studied against streptozotocin (STZ) (50 mg/kg; i.p.) + nicotinamide (120 mg/kg; i.p.) induced diabetes mellitus. The animals were treated with the investigational plant extract and standard drug (glibenclamide) for 21 consecutive days and the effect of hydroalcoholic extract of O. tenuiflorum on blood glucose levels was measured at regular intervals. At the end of the study, blood samples were collected from all the animals for biochemical estimation, then the animals were sacrificed and the liver and kidney were collected for organ weight analysis. Prediction for pharmacological and toxicological properties of phytoconstituents of O. tenuiflorum was carried out using online web tools such as online pass prediction and lazar toxicity prediction. RESULTS: The hydroalcoholic extract of O. tenuiflorum showed significant anti-diabetic and anti-hyperlipidemic activity at 250 and 500 mg/kg, and this effect was comparable with that of glibenclamide. Predicted biological activities of phytoconstituents of O. tenuiflorum showed presence of various pharmacological actions, which includes anti-diabetic and anti-hyperlipidemic activities. Prediction of toxicological properties of phytoconstituents of O. tenuiflorum did not show any major toxic effects. CONCLUSION: The hydroalcoholic extract of O. tenuiflorum showed significant anti-diabetic and anti-hyperlipidemic activity against STZ + nicotinamide induced diabetes mellitus in rats. Further studies are required to confirm the anti-diabetic and anti-hyperlipidemic activities of individual phytoconstituents of O. tenuiflorum.

A retrospective study on the incidences of adverse drug events and analysis of the contributing trigger factors.

OBJECTIVES: To retrospectively determine the extent and types of adverse drug events (ADEs) from the patient cases sheets and identify the contributing factors of medication errors. To assess causality and severity using the World Health Organization (WHO) probability scale and Hartwig's scale, respectively. METHODS: Hundred patient case sheets were randomly selected, modified version of the Institute for Healthcare Improvement (IHI) Global Trigger Tool was utilized to identify the ADEs; causality and severity were calculated utilizing the WHO probability scale and Hartwig's severity assessment scale, respectively. RESULTS: In total, 153 adverse events (AEs) were identified using the IHI Global Trigger Tool. Majority of the AEs are due to medication errors (46.41%) followed by 60 adverse drug reactions (ADRs), 15 therapeutic failure incidents, and 7 over-dose cases. Out of the 153 AEs, 60 are due to ADRs such as rashes, nausea, and vomiting. Therapeutic failure contributes 9.80% of the AEs, while overdose contributes to 4.58% of the total 153 AEs. Using the trigger tools, we were able to detect 45 positive triggers in 36 patient records. Among it, 19 AEs were identified in 15 patient records. The percentage of AE/100 patients is 17%. The average ADEs/1000 doses is 2.03% (calculated). CONCLUSION: The IHI Global Trigger Tool is an effective method to aid provisionally-registered pharmacists to identify ADEs quicker.