Ebola Hemorrhagic Fever: Recent Update On Disease Status, Current Therapies And Advances In Treatment

Swiftly growing viruses are a major intimidation to human health. Such viruses are extremely pathogenic like Ebola virus, influenza virus, HIV virus, Zika virus etc . Ebola virus, a type of Filovirus, is an extremely infectious, single-stranded ribonucleic acid virus that infects both humans and apes, prompting acute fever with hemorrhagic syndrome. The high infectivity, severity and mortality of Ebola has plagued the world for the past fifty years with its first outbreak in 1976 in Marburg, Germany, and Frankfurt along with Belgrade and Serbia. The world has perceived about 28,000 cases and over 11,000 losses. The high lethality of Ebola makes it a candidate for use in bioterrorism thereby arising more concern. New guidelines have been framed for providing best possible care to the patients suffering from Ebola virus i.e Grading of Recommendation Assessment, Development And Evaluation (GRADE) methodology to develop evidence-based strategy for the treatment in future outbreak of Ebola virus. No drugs have been approved, while many potent drugs like rVSV-EBOV, Favipiravir, ZMapp are on clinical test for human safety. In this review we will discover and discuss perspective aspects that lead to the evolution of different Ebola variants as well as advances in various drugs and vaccines for treatment of the disease

Role of Protein Kinase C in Diabetic Complications

Diabetes is the most common and systemic disorder associated with hyperglycemia which is the significant factor in the development of micro- and macrovascular changes. Many mechanistic approaches i.e. activation of Protein kinase C, glycation end products production, hexosamine pathway and polyol pathway induce cellular damage and lead to the development of diabetic complications like nephropathy, neuropathy, retinopathy, and myopathy. One of the adverse effects of long-lasting hyperglycemia is activation of PKC (intracellular signaling enzyme) and has become a field of great research interest. Hence, in this review special emphasis is placed on microvascular complications which are due to activation of PKC. Clinical trials have also been conducted using selective PKC inhibitors and have shown positive results against hyperglycemia

Ranitidine Induced Hepatotoxicity: A Review

Background: Ranitidine (RAN) is one of the common drugs associated with idiosyncratic adverse drug reactions (IADRs) in humans. It was found to be associated with severe adverse drug reactions due to the presence of contaminants such as N-Nitrosodimethylamine (NDMA) which is claimed to be carcinogenic. As a consequence, on April 1, 2020, United States Food and Drug Administration (USFDA) had decided to call off all the RAN products from the market. The exact cause of RAN associated idiosyncratic hepatotoxicity is not clear yet. Purpose: To summarize and analyze the reason behind the withdrawal of RAN products from the market and whether ranitidine will be available again in future or will FDA withdraw approvals of ranitidine National Drug Authority (NDA) and an abbreviated new drug application (ANDA)? Methods: We performed a systematic PubMed/MEDLINE search of studies investigating the reason behind the withdrawal of RAN products and explored the possible mechanism associated with RAN induced hepatotoxicity.Conclusion: RAN induced liver injury is difficult to diagnose and study because of its relative rarity and unpredictive occurrence. Recent studies suggest that most of the RAN associated idiosyncratic reactions may lead to hepatocyte damage, followed by a series of events, such as activation of specific T- and B-cells, release of proinflammatory mediators like TNFα, interleukins, various cytokines and chemokines. The exact cause of RAN associated idiosyncratic hepatotoxicity is not clear yet. More studies must be carried out on this to know about the exact reason behind RAN associated hepatotoxicity

DEVELOPMENT AND CHARACTERIZATION OF ORO-DISPERSIBLE TABLETS OF METFORMIN HYDROCHLORIDE USING CAJANUS CAJAN STARCH AS A NATURAL SUPERDISINTEGRANT

Objective: The aim of the research work was to explore the use of Cajanus cajan (Pigeon pea) polysaccharide as a superdisintegrant. The novel superdisintegrant has been evaluated for its action by incorporating it into orodispersible tablets of Metformin Hydrochloride. Methods: Cajanus cajan starch was extracted from its seeds and superdisintegrant was developed by microwave modification of the extract. Various characterization tests such as gelatinization temperature, water absorption index, pH, and viscosity were used to identify the microwave-modified polysaccharide. The orodispersible tablets were made using a direct compression process employing varying concentrations of modified Cajanus cajan starch. Prepared tablets were tested for several pre and post-compression parameters and compared with a well-established synthetic superdisintegrant, sodium starch glycolate. The stability studies were conducted on an optimized formulation. Results: Fourier transform infrared spectroscopy study showed that the drug had no interactions with the microwave-modified Cajanus cajan starch. SEM confirmed that Cajanus cajan starch granules exhibited intact granular structure in oval shapes and smooth surfaces. After microwave modification, the Cajanus cajan starch component lost its granular structure, which further led to the generation of surface pores and internal channels, causing overall swelling responsible for superdisintegrant activity. The optimized formulation (ODF5) containing 15 % modified Cajanus cajan starch performed better in terms of wetting time (22.21 s), disintegration time (53.3 s), and in vitro drug release (92%), as compared to formulation prepared by synthetic superdisintegrant (ODF1). Conclusion: The present investigation concluded that modified Cajanus cajan starch has good potential as a superdisintegrant for formulating oro-dispersible tablets. Furthermore, modified Cajanus cajan starch is inexpensive, non-toxic and compatible in comparison with available synthetic superdisintegrants

Histone Deacetylase Inhibitors As Potential Therapeutic Agents For Various Disorders

Epigenetic modification acetylation or deacetylation of histone considered as an important element in various disorders. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) are the enzymes which catalyse the acetylation and deacetylation of histone respectively. It helps in regulating the condensation of chromatin and transcription of genes. Lysine acetylation and deacetylation present on the nucleosomal array of histone is the key factor for gene expression and regulation in a normal working living cell. Modification in histone protein will lead to the development of cancer and can cause various neurodegenerative disorders. To safeguard the cells or histone proteins from these diseases histone deacetylase inhibitors are used. In this review, the main focus is upon the role of histone deacetylases inhibitors in various diseases

Improved antibacterial activity of topical gel-based on nanosponge carrier of cinnamon oil

Introduction: Cinnamon essential oil (CEO) is a volatile oil, obtained from Cinnamomum zeylanicum has become one of the most important natural oil due to its antimicrobial activity. CEO suffers from various limitations such as instability and skin irritation. This problem has been overcome by formulating CEO-loaded nanosponges incorporated in carbopol gel with increased antimicrobial property and reduced skin irritation. Methods: The nanosponges were fabricated by solvent emulsion diffusion method and evaluated for Fourier transform infrared spectroscopy (FTIR) studies, particle size, field emission scanning electron microscopy studies (FE-SEM), in vitro dissolution studies, in vitro antibacterial studies, using agar diffusion method, in vivo antibacterial activity and skin irritation studies and stability studies. Results: Nanosponge NS1 batch was found to be in the nanosize range. FTIR studies confirmed the absence of drug-polymer interaction. NS1 confirmed a porous structure with a uniform spherical shape using FE-SEM studies. In vitro dissolution studies of optimized NS1 revealed 80% drug release in 5 h whereas, incorporating the formulation into carbopol gel showed 100% release in 5h from G1 formulation. In vitro antibacterial study of the nanosponge (NS1 and NS3) showed remarkable antibacterial activity as seen from the zone of inhibition and gel formulation G1 also showed the highest zone of inhibition with 50±1.2 mm. NS1 and G1 were stable for 2 months under accelerated conditions and 3 months under room temperature conditions. Furthermore, the in vivo and skin irritation studies were performed with selected formulation against Staphylococcus aureus, where the results confirmed the significant antimicrobial activity with no skin irritation. Conclusion: Nanosponge carriers can be more therapeutically effective for essential oils which can further be incorporated into topical gels for convenient application

Phytochemical investigations, in-vitro antioxidant, antimicrobial potential, and in-silico computational docking analysis of Euphorbia milii Des Moul

Euphorbia milii Des Moul is a deciduous bush indigenous to Madagascar. The present study aims to investigate the presence of the phytochemical, in-vitro antioxidant and antimicrobial potency, and in-silico computational analysis of ethanolic and aqueous preparations of E. milii leaves and flowers. The ethanolic and aqueous extracts were tested for in-vitro antioxidant activity by DPPH, H2O2, TAC, and FRAP assay. In addition, antimicrobial potentials were assayed by agar well diffusion technique against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, and Candida albicans for various clinical isolates. The qualitative phytochemical analysis results confirmed the existence of alkaloids, flavonoids, phenolics, and tannins. The quantitative analysis elicits the availability of a magnificent number of alkaloids, flavonoids, phenolics, flavonols, and tannins. Among all the extracts, aqueous extracts of leaves exhibited potent antioxidant activity in DPPH, FRAP, and H2O2 assay with the IC50 value of 30.70, 60.05, and 82.92µg/mL, respectively. In agar well diffusion assay, all extracts displayed zone of inhibition varies from 2-24mm at different concentrations ranging from 10-320 mg/mL, whereas no activity was observed against Candida albicans. Furthermore, docking-based computational analysis has revealed that beta-sitosterol and taraxerol are the plant's active constituents responsible for their antimicrobial and antioxidant activities. Research findings suggest that the E. milii plant has an excellent prospect for further study for its extended antioxidative and antimicrobial potential. It could be a natural source of various ailments and can be utilized to develop new drugs

Development of a novel HPTLC fingerprint method for simultaneous estimation of berberine and rutin in medicinal plants and their pharmaceutical preparations followed by its application in antioxidant assay

The present study was designed to develop and validate a high-performance thin-layer chromatography (HPTLC) system for the simultaneous quantitative determination of berberine and rutin in Tinospora cordifolia extract and their pharmaceutical preparations. Chromatographic development was done using a blend of n-hexane, ethyl acetate, glacial acetic acid and methanol (10:1.1:1.1:2.5, v/v) as the mobile phase. Detection was completed densitometrically at 254 nm. The RF estimation of berberine and rutin was observed to be 0.67 ± 0.02 and 0.47 ± 0.02, respectively. The developed HPTLC method was validated according to ICH guidelines; the method was specific, linear and accurate and can be used to determine berberine and rutin in marketed herbal preparations. The Tinospora cordifolia plant extract was further evaluated for antioxidant activity using HPTLC, and berberine was found to be more active than rutin during DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging activity. The method was found simple, rapid, accurate, specific and robust for the analysis of berberine and rutin in crude drug using the same method

Hypoxia-inducible factor (HIF): fuel for cancer progression

Hypoxia is an integral part of the tumor microenvironment, caused primarily due to rapidly multiplying tumor cells and a lack of proper blood supply. Among the major hypoxic pathways, HIF-1 transcription factor activation is one of the widely investigated pathways in the hypoxic tumor microenvironment (TME). HIF-1 is known to activate several adaptive reactions in response to oxygen deficiency in tumor cells. HIF-1 has two subunits, HIF-1β (constitutive) and HIF-1α (inducible). The HIF-1α expression is largely regulated via various cytokines (through PI3K-ACT-mTOR signals), which involves the cascading of several growth factors and oncogenic cascades. These events lead to the loss of cellular tumor suppressant activity through changes in the level of oxygen via oxygen-dependent and oxygenindependent pathways. The significant and crucial role of HIF in cancer progression and its underlying mechanisms have gained much attention lately among the translational researchers in the fields of cancer and biological sciences, which have enabled them to correlate these mechanisms with various other disease modalities. In the present review, we have summarized the key findings related to the role of HIF in the progression of tumors

Effects of Resveratrol Postconditioning on Cerebral Ischemia in mice: Role of the Sirtuin-1 (SIRT1) Pathway

Evidence has demonstrated that resveratrol preconditioning exhibits neuroprotection against cerebral IR injury. The current investigation aimed to explore whether pharmacological postconditioning, by administering resveratrol, after a sustained ischemia prior to prolonged reperfusion abrogates cerebral IR injury. Cerebral ischemia-reperfusion-induced injury mice model was employed in this study to evaluate the neuroprotective effects of pharmacological postconditioning (pPoCo) with resveratrol (30 mg/kg; i.p.) administered 5 mins before reperfusion. We administered Sirtinol, a SIRT1/2 selective inhibitor (10 mg/kg; i.p.) 10 min before ischemia (17 min) and reperfusion (24 h), to elucidate whether the neuroprotection with resveratrol postconditioning depends on SIRT1 activation. Various biochemical, behavioral parameters and histopathological changes were assessed to examine the effect of pPoCo. Infarct size is estimated using TTC staining. It was established that resveratrol postconditioning abrogated the deleterious effects of IR injury expressed with regard to biochemical parameters of oxidative stress (TBARS, SOD, GSH), acetylcholinestrase activity, behavioual parameters (memory, motor coordination), infarct size and histopathological changes. Sirtinol significantly reversed the effect of resveratrol PoCo. We conclude that induced neuroprotective benefits of resveratrol postconditiong may be the consequence of SIRT1 activation and resveratrol can be considered, for further studies, as potential agent inducing pharmacological postconditioning in clinical situations.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author