Anti-HSV activity of nectin-1-derived peptides targeting HSV gD: an in-silico and in-vitro approach.

Herpes simplex virus (HSV) infections affect a wide range of the global population. The emergence of resistance to the existing anti-HSV therapy highlights the necessity for an innovative strategy. The interaction of HSV gD with its main host receptor nectin-1 is a potential target for new antiviral drugs. The aim of this study was to develop a peptide derived from nectin-1 targeting HSV gD using the in-silico method and evaluate them for anti-HSV activity. Residues 59-133 of the Nectin-1 V-domain constitute the interaction interface with HSV gD. Bioinformatic tools viz., PEP-FOLD3, ClusPro 2.0, HawkDock and Desmond were used to model the peptide and confirm its binding specificity with HSV gD protein. The peptides with potential interactions were custom synthesized and anti-HSV activity was evaluated in vitro against HSV-1 and HSV-2 by CPE inhibition assay. Five peptide sequences were identified as exhibiting good interaction with HSV-gD proteins. Among them, peptide N1 (residues 76-90) offered maximum protection against HSV-1 (66.57%) and HSV-2 (71.12%) infections. Modification of the identified peptide through peptidomimetic approaches may further enhance the activity and stability of the identified peptide.Communicated by Ramaswamy H. Sarma.

Revamped mini-αA-crystallin showed improved skin permeation and therapeutic activity against melittin-induced toxicity.

Melittin is honey bee venom's primary and most toxic pharmacologically active component. Melittin causes haemolysis, lymphocyte lysis, long-term pain, localised inflammation followed by rhabdomyolysis, and severe renal failure. Renal failure or cardiovascular complications could lead to the victim's death. Severe honey bee bites are treated with general medication involving antihistaminic, anti-inflammatory, and analgesic drugs, as a specific treatment option is unavailable. An earlier study showed the anti-hemolysis and anti-lymphocyte lysis activity of mini- αA-crystallin (MAC), a peptide derived from human eye lens alpha-crystallin. MAC's use has often been restricted despite its high therapeutic potential due to its poor skin permeability. This study compared the skin permeation, anti-inflammatory and analgesic activities of natural peptide MAC and its modified version (MAC-GRD) formed by attaching cell-penetrating peptide (CPP) and GRD amino residues into MAC. Gel formulations were prepared for MAC and MAC-GRD peptides using carbopol (1% w/w), Tween 80 (1%), and ethanol (10%). An ex-vivo skin permeation study was performed using a vertical-type Franz diffusion apparatus. Preclinical in-vivo experiments were conducted to compare the native and modified peptide formulations against melittin-induced toxicity in Wistar rats. MAC gel, MAC-GRD gel and 1% hydrocortisone cream significantly reduced the melittin-induced writhing (20.16 ± 0.792) response in rats with 15.16 ± 0.47, 11.16 ± 0.477 and 12.66 ± 0.66 wriths, respectively. There was a significant reduction in melittin-induced inflammation when MAC-GRD gel was applied immediately after melittin administration. At 0.5, 1, 3, and 5 h, the MAC-GRD-treated rat paws were 0.9 ± 0.043 mm, 0.750 ± 0.037 mm, 0.167 ± 0.0070 mm, and 0.133 ± 0.031 mm thick. Administration of melittin resulted in reduced GSH (antioxidant) levels (47.33 ± 0.760 µg/mg). However, treatment with MAC-GRD gel (71.167 ± 0.601 µg/mg), MAC gel (65.167 ± 1.138 µg/mg), and 1% hydrocortisone (68.33 ± 0.667 µg/mg) significantly increased the antioxidant enzyme levels. MAC-GRD gel significantly reduced the elevated MDA levels (6.933 ± 0.049 nmol/mg) compared to the melittin group (12.533 ± 0.126 nmol/mg), followed by the 1% hydrocortisone (7.367 ± 0.049 nmol/mg) and MAC gel (7.917 ± 0.048 nmol/mg). MAC-GRD demonstrated more skin permeability and superior anti-inflammatory, analgesic, and antioxidant activities when compared to MAC gel. When compared to standard 1% hydrocortisone cream, MAC-GRD had better anti-inflammatory, analgesic, antioxidant, and comparable action in anti-oxidant restoration against melittin. These findings suggest that the developed MAC-GRD gel formulation could help to treat severe cases of honey bee stings.

Treatment of H. pylori infection and gastric ulcer: Need for novel Pharmaceutical formulation.

Peptic ulcer disease (PUD) is one of the most prevalent gastro intestinal disorder which often leads to painful sores in the stomach lining and intestinal bleeding. Untreated Helicobacter pylori (H. pylori) infection is one of the major reasons for chronic PUD which, if left untreated, may also result in gastric cancer. Treatment of H. pylori is always a challenge to the treating doctor because of the poor bioavailability of the drug at the inner layers of gastric mucosa where the bacteria resides. This results in ineffective therapy and antibiotic resistance. Current treatment regimens available for gastric ulcer and H. pylori infection uses a combination of multiple antimicrobial agents, proton pump inhibitors (PPIs), H2-receptor antagonists, dual therapy, triple therapy, quadruple therapy and sequential therapy. This polypharmacy approach leads to patient noncompliance during long term therapy. Management of H. pylori induced gastric ulcer is a burning issue that necessitates alternative treatment options. Novel formulation strategies such as extended-release gastro retentive drug delivery systems (GRDDS) and nanoformulations have the potential to overcome the current bioavailability challenges. This review discusses the current status of H. pylori treatment, their limitations and the formulation strategies to overcome these shortcomings. Authors propose here an innovative strategy to improve the H. pylori eradication efficiency.

Small extracellular vesicle-loaded bevacizumab reduces the frequency of intravitreal injection required for diabetic retinopathy.

Diabetic retinopathy (DR) is associated with retinal neovascularization, hard exudates, inflammation, oxidative stress and cell death, leading to vision loss. Anti-vascular endothelial growth factor (Anti-VEGF) therapy through repeated intravitreal injections is an established treatment for reducing VEGF levels in the retina for inhibiting neovascularization and leakage of hard exudates to prevent vision loss. Although anti-VEGF therapy has several clinical benefits, its monthly injection potentially causes devastating ocular complications, including trauma, intraocular hemorrhage, retinal detachment, endophthalmitis, etc. Methods: As mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) demonstrated safety in clinical studies, we have tested the efficacy of MSC-derived small EVs (MSC-sEVs) loaded anti-VEGF drug bevacizumab in a rat model of DR. Results: The study identified a clinically significant finding that sEV loaded with bevacizumab reduces the frequency of intravitreal injection required for treating diabetic retinopathy. The sustained effect is observed from the reduced levels of VEGF, exudates and leukostasis for more than two months following intravitreal injection of sEV loaded with bevacizumab, while bevacizumab alone could maintain reduced levels for about one month. Furthermore, retinal cell death was consistently lower in this period than only bevacizumab. Conclusion: This study provided significant evidence for the prolonged benefits of sEVs as a drug delivery system. Also, EV-mediated drug delivery systems could be considered for clinical application of retinal diseases as they maintain vitreous clarity in the light path due to their composition being similar to cells.

Femoral Artery Injuries in Closed Femur Shaft Fractures: Case Report.

Case 1 and 2 Two young male patients, sustained injury to the superficial femoral artery (SFA) following a closed femur shaft fracture. The arterial injuries were confirmed by computed tomography angiography and both underwent fracture fixation and on SFA exploration; a thrombosed arterial segment was noted at the fracture site, addressed with arteriotomy and thrombectomy to restore the vascularity. At 1-year follow-up, both patients had good union at the fracture site and a well-perfused limb. Conclusion Thorough clinical examination and appropriate diagnostic studies can diagnose these rare vascular injuries in closed fractures and with early vascular repair potentially limb-threatening complications can be prevented.

Phytotherapeutics against Alzheimer's Disease: Mechanism, Molecular Targets and Challenges for Drug Development.

Alzheimer's disease is inflating worldwide and is combatted by only a few approved drugs. At best, these drugs treat symptomatic conditions by targeting cholinesterase and N-methyl- D-aspartate receptors. Most of the clinical trials in progress are focused on developing disease-modifying agents that aim at single targets. The 'one drug-one target' approach is failing in the case of Alzheimer's disease due to its labyrinth etiopathogenesis. Traditional medicinal systems like Ayurveda use a holistic approach encompassing the legion of medicinal plants exhibiting multimodal activity. Recent advances in high-throughput technologies have catapulted the research in the arena of Ayurveda, specifically in identifying plants with potent anti-Alzheimer's disease properties and their phytochemical characterization. Nonetheless, clinical trials of very few herbal medicines are in progress. This review is a compendium of Indian plants and ayurvedic medicines against Alzheimer's disease and their paraphernalia. A record of 230 plants that are found in India with anti-Alzheimer's disease potential and about 500 phytochemicals from medicinal plants have been solicited with the hope of exploring the unexplored. Further, the molecular targets of phytochemicals isolated from commonly used medicinal plants, such as Acorus calamus, Bacopa monnieri, Convolvulus pluricaulis, Tinospora cordifolia and Withania somnifera, have been reviewed with respect to their multidimensional property, such as antioxidant, anti-inflammation, anti-aggregation, synaptic plasticity modulation, cognition, and memory-enhancing activity. In addition, the strengths and challenges in ayurvedic medicine that limit its use as mainstream therapy are discussed, and a framework for the development of herbal medicine has been proposed.

Statistical optimisation of polyhydroxyalkanoate production in Bacillus endophyticus using sucrose as sole source of carbon.

Microorganisms have been contemplated as a promising source for the inexhaustible synthesis of many novel materials utilizing renewable sources. Among many of such products, polyhydroxyalkanoate (PHA) remains as an essential biodegradable polymer with functions similar to conventional plastics. Bacillus endophyticus is capable of accumulating biopolymer PHA in nutrient limiting conditions with excess of carbon source. Screening and optimizing the parameters for increased PHA production was done statistically. The optimized medium gave a maximum yield of 46.57% which was in well agreement with the given predicted value provided by response surface methodology model yield of 47.02%. Optimal media conditions when extrapolated in bioreactor gave an even higher production percentage of 49.9. This is the first report highlighting 49% of polyhydroxybutyrate statistically using sucrose as a source. The main highlight of the study was the use of wild type strain for producing high quality PHA using simple carbon source which can be a starting platform for using this strain for large scale PHA production industrially. FTIR and 1HNMR analysis confirmed the polymer produced.

Statistical Optimization for Coproduction of Chitinase and Beta 1, 4-Endoglucanase by Chitinolytic Paenibacillus elgii PB1 Having Antifungal Activity.

A bacterial strain PB1 with antagonistic activity against pathogenic fungi was isolated from marine soil and was identified as Paenibacillus elgii based on phenotypic and genotypic characterization. The isolate showed good antifungal activity against "Aspergillus niger (MTCC 282), Trichophyton rubrum (MTCC 791), Microsporum gypseum (MTCC 2819), Candida albicans (MTCC 227), and Saccharomyces cerevisiae (MTCC 170)". Chitinase and beta 1, 4-endoglucanase are known for their capability to degrade fungal cell wall, thus we analyzed its productivity in PB1 strain using Plackett-Burman and Central Composite Design. The factors that affect the productivity of chitinase and beta 1, 4-endoglucanase were identified and optimized. A 7.77-fold increase (3.157 to 24.53 ± 1.33 U/mL) in chitinase and 7.422-fold increase (6.476 to 48.066 ± 0.676 U/mL) in beta 1, 4-endoglucanase versus basal medium was achieved. Chitinase and beta 1, 4-endoglucanase produced by Paenibacillus elgii strain PB1 represents the new source for biotechnological, medical, and agricultural applications.

Prolonged reaction to mental arithmetic stress in first-degree relatives of schizophrenia patients.

OBJECTIVE: Several studies have reported abnormal heart rate variability (HRV) in schizophrenia patients, suggesting a pathophysiological link between central autonomic dysfunction and symptoms of schizophrenia and that these could be heritable. This study aimed at evaluating cardiac autonomic response to mental arithmetic stress in first-degree relatives of schizophrenia patients (FDRS) employing HRV analysis. METHODS: HRV measures were computed for 25 healthy FDRS and 25 age- and gender-matched controls during rest, mental arithmetic stress task and recovery period. Subtracting serial sevens from 700 for five minutes formed the stress task. Recovery period lasted five minutes starting from the termination of the stress task. RESULTS: Both groups showed similar alterations during the stress task. After stress termination, recovery to the basal values was observed in controls but not in patients' relatives, maintaining a pattern similar to that during the stress task. CONCLUSIONS: Poor recovery from cardiac autonomic functions (CAF) alterations induced by arithmetic stress may be a heritable trait marker of schizophrenia. Our report supports endophenotypic potential of HRV in schizophrenia research.

Psychiatric morbidity among patients with oral submucous fibrosis: a controlled study.

AIM: The study aimed to evaluate the association between oral submucous fibrosis (OSF) and psychiatric morbidity in a controlled manner. METHODS: Matched patients were divided into three groups: Those with areca nut chewing habits with OSF (Group 1; n=50); those with areca nut chewing habits without OSF (Group 2; n=50); those without areca habits and with dental problems other than OSF (Group 3; n=50). The Mini International Neuropsychiatric Interview was used to assess psychiatric morbidity. Dependence to areca products was also assessed. RESULTS: Sixteen (32%) Group 1 patients had psychiatric morbidity compared to one (2%) in Group 2 and two (4%) in Group 3 (P<0.001). Further, psychiatric morbidity was significantly higher among patients with advanced stages of OSF. In Groups 1 and 2, 49 (98%) and 47 (94%) patients, respectively, had dependence on areca products. CONCLUSION: This study has suggested the association of substantial psychiatric morbidity among patients with OSF. In addition to mandatory psychiatric management of these patients, future research should be targeted at a prospective evaluation of a cause and effect relationship as well as at psychiatric interventions.

Psychiatric morbidity among patients with oral sub-mucous fibrosis: a preliminary study.

BACKGROUND: Oral submucous fibrosis (OSF) is a chronic oral mucosal condition with pre-malignant potential. The association between psychiatric morbidity and OSF has been sparsely studied. METHODS: This cross-sectional study included 33 consecutive subjects clinically diagnosed with OSF who attended an academic tertiary care dental centre. General Health Questionnaire-28 was administered to assess the psychological morbidity. Dependence to areca products was assessed using the ICD-10 criteria. Patient group was compared with an age and gender matched control group (n=33) from the same hospital that comprised patients who had dental diseases other than OSF and had no areca/tobacco habit. RESULTS: Total mean scores (SD) of GHQ-28 for study group and control group respectively were 48.2 (18.1) vs. 24.2 (6.5) (P<0.001). Among the patient group, the mean total GHQ scores were significantly higher in those with functional stage C (those with worst functional staging) of OSF 63.4 (15.2) when compared with those with stage B 54 (14.2) and stage A 38.7 (17) (d.f.=2; P=0.005). 22 (66.7%) of patients met ICD-10 criteria for dependence to areca products. CONCLUSIONS: OSF may be associated with considerable psychological morbidity. This morbidity may be significantly more in patients with worst functional staging. It is difficult to determine whether this is the cause or effect of the disease. Further systematic studies are urgently needed to address this issue.

Psychiatric rehabilitation.

Psychiatric rehabilitation is an important component in the management of the mentally ill. This article presents a selective review of the publications in this journal. Questions addressed in this review range from assessment of rehabilitation needs to different rehabilitative approaches. Although the number of publications providing the answers is meager, there are innovative initiatives. There is a need for mental health professionals to publish the models they follow across the country.

Disabilities research in India.

The objective of this paper is to review all articles related to psychiatric disability that have been published in the Indian Journal of Psychiatry since its inception till date. We have also added up some more relevant literature in the area of mental disability of Indian psychiatric patients. Finally the article ends up with discussion related to challenges associated with mental disability, persons with Disability Act and future directions in the area of psychiatric disability.

T2 relaxometry of ring lesions of the brain.

AIM: To differentiate two common aetiologies of "ring lesions," tuberculomas and cysticercal cysts, using T2 relaxometry. MATERIALS AND METHODS: Fifty-five ring-enhancing lesions of the brain (32 cysticercal cysts; 23 tuberculomas) in 27 patients with focal seizures were studied for T2 relaxation times. RESULTS: The mean T2 relaxation times of cysticercal cysts was 617 ms (range 305-1365 ms; SD 272.2) and that of tuberculomas 161 ms (range 83-290 ms; SD 60.3; 95% confidence). CONCLUSION: T2 relaxometry is a simple, reliable and valuable non-invasive magnetic resonance imaging (MRI) technique to differentiate between intracranial cysticercal cysts and tuberculomas, and may be incorporated in routine diagnostic protocols.

Restricted diffusion in Canavan disease.

INTRODUCTION: Canavan disease is a megalencephalic leukodystrophy due to deficiency of the enzyme aspartoacylase. Proton MR spectroscopy finding of elevated N-acetyl-L: -aspartate is considered diagnostic of Canavan disease. CASE REPORT: We report a case of Canavan disease, which showed restricted diffusion in diffusion-weighted imaging and discuss the cause of it.

Middle meningeal arteriovenous fistula and its spontaneous closure. A case report and review of the literature.

SUMMARY: Middle meningeal artery pseudo-aneurysms and arteriovenous fistulas are usually post-traumatic, although occasional iatrogenic cases have been reported. The treatment has been obliteration of the fistula by surgical or endovascular means. Spontaneous closure of fistula is uncommon. We report a case of non-traumatic middle meningeal arteriovenous fistula in a patient with alcoholism, which resolved spontaneously without treatment.

Unilateral Moyamoya Phenomenon Due to MCA Occlusion in a Child Presenting with Intracerebral Hemorrhage.

SUMMARY: Spontaneous middle cerebral artery (MCA) occlusion leading to moyamoya phenomenon is different from classical moyamoya disease. Previous studies have reported such phenomena in adults with ischemic lesions, except for a solitary case in a child.We report a case of a ten-year old girl who presented with a deep intracerebral hematoma and a normal ipsilateral middle cerebral artery on initial evaluation by CT. Subsequently, on follow-up angiography, the ipsilateral MCA was occluded with evidence of unilateral basal lenticulostriate and transdural collateral supply causing a 'moyamoya' phenomenon. This report discusses a rare and interesting disease from the perspective of 'moyamoya' phenomenon and angiogenesis.