Evaluating the inhibitory potential of Withania somnifera on platelet aggregation and inflammation enzymes: An in vitro and in silico study

Context Withania somnifera (L.) Dunal is traditionally used for treating various ailments, but lacks scientific evaluation.

Objective This study evaluates Withania somnifera (WS) for its effect on platelet activity and inflammatory enzymes.

Materials and methods Aqueous and ethanolic (1:1) leaf extracts were subjected to in vitro indirect haemolytic activity using Naja naja venom, human platelet aggregation was quantified for lipid peroxidation using arachidonic acid (AA) as agonist and 5-lipoxygenase (5-LOX) levels were determined using standard spectrometric assays. Further, molecular docking was performed by the ligand fit method using molegro software package (Molegro ApS, Aarhus, Denmark).

Results The study found that aqueous and ethanol extracts have very negligible effect (15%) with an IC₅₀ value of 13.8?mg/mL on PLA₂ from Naja naja venom. Further, extracts of WS also had very little effect (18%) with an IC₅₀ value of 16.6?mg/mL on malondialdehyde (MDA) formation. However, a 65% inhibition of 5-LOX with an IC₅₀ value of 0.92?mg/mL was observed in 1:1 ethanol extracts. The same was evident from SAR model with the active ingredient withaferin A binding predominantly on Phe 77, Tyr 98, Arg 99, Asp 164, Leu 168, Ser 382, Arg 395, Tyr 396 and Tyr 614 with an atomic contact energy value of??128.96 compared to standard phenidone (?103.61). Thus, the current study validates the application of WS for inflammatory diseases.

Conclusion This study reveals the inhibitory potential of W. somnifera on inflammatory enzymes and platelet aggregation. Thus, WS can serve as a newer, safer and affordable medicine for inflammatory diseases.     

Autoimmune hepatitis: a study of 50 patients.

INTRODUCTION: Autoimmune hepatitis (AIH) is a well-defined entity in the West but there are sparse Indian data on this disease. AIM: To study the clinical profile and response to treatment of Indian patients with AIH. METHODS: This is a part retrospective and part prospective study of 50 patients (median age 48 years, range 11-82; 43 women) seen between 1995 to 2001, diagnosed to have AIH as per the revised scoring system. Clinical and laboratory profile, response to treatment, and complications of treatment were analyzed. RESULTS: AIH accounted for 6% of all patients with liver disease seen during the period. The presenting symptoms were gastrointestinal in 43 and non-gastrointestinal in 7, with median symptom duration of 6 months (range 2 weeks to 40 years). Forty patients (80%) had chronic liver disease. Associated illnesses were present in 28 patients. Twenty-six patients were classified as definite and the rest as probable AIH. Forty-nine patients had Type 1 AIH. Five patients had overlap syndrome. Forty-five patients (90%) received immunosuppressive therapy. Twelve of 18 patients receiving only prednisolone and 21 of 27 patients receiving prednisolone and azathioprine combination responded. Thirteen (26%) patients had therapy-related complications (infectious 5, non infectious 8) with two treatment-related deaths. CONCLUSION: Type 1 AIH was the predominant type of AIH. The majority of patients with AIH presented with chronic liver disease. There was good response to immunosuppressive therapy. Therapy-related complications occurred in one-fourth of patients.     

Isolation and analysis of partial cDNA sequence coding for superoxide dismutase in Wuchereria bancrofti.

Molecular characterization of Wuchereria bancrofti is essential to develop suitable anti-filarial drugs and vaccines. We describe here isolation, sequence analysis and cloning of a partial cDNA of an enzyme superoxide dismutase from this parasite. The immunoscreening of a lambda zap W. bancrofti microfilarial (Mf) cDNA library with microfilaremic sera had resulted in the isolation of several seroreactive clones including, WbSOD. This clone contained a 309 bp insert and showed significant nucleotide and deduced amino acid sequence homologies to the superoxide dismutases of other nematode parasites. The antioxidant property of this enzyme may have important contribution in the defense mechanism of the parasite against host immune response.     

Localization of arboviral antigen in brain tissues from patients with encephalitis

Brain tissues from 38 patients with a clinical suspicion of encephalitis or encephalopathy were examined by two immunoenzymatic techniques for the detection of arboviral antigen. Group B arboviral antigen was identified in 23 of these tissues. This simple method could be used for the diagnosis of the causal agent of encephalitis.     

Unilateral congenital elongation of the cervical part of the internal carotid artery with kinking and looping: two case reports and review of the literature

Unilateral and bilateral variation in the course and elongation of the cervical (extracranial) part of the internal carotid artery (ICA) leading to its tortuosity, kinking and coiling or looping is not a rare condition, which could be caused by both embryological and acquired factors. Patients with such variations may be asymptomatic in some cases; in others, they can develop cerebrovascular symptoms due to carotid stenosis affecting cerebral circulation. The risk of transient ischemic attacks in patients with carotid stenosis is high and its surgical correction is indicated for the prevention of ischemic stroke. Detection of developmental variations of the ICA and evaluation of its stenotic areas is very important for surgical interventions and involves specific diagnostic imaging techniques for vascular lesions including contrast arteriography, duplex ultrasonography and magnetic resonance angiography. Examination of obtained images in cases of unusual and complicated variations of vascular pattern of the ICA may lead to confusion in interpretation of data. Awareness about details and topographic anatomy of variations of the ICA may serve as a useful guide for both radiologists and vascular surgeons. It may help to prevent diagnostic errors, influence surgical tactics and interventional procedures and avoid complications during the head and neck surgery. Our present study was conducted with a purpose of updating data about developmental variations of the ICA. Dissections of the main neurovascular bundle of the head and neck were performed on a total 14 human adult cadavers (10 – Africans: 7 males & 3 females and 4 – East Indians: all males). Two cases of unilateral congenital elongation of the cervical part of the ICA with kinking and looping and carotid stenoses were found only in African males. Here we present their detailed case reports with review of the literature.     

Role of delayed enhancement MRI in patients with acute coronary syndrome and unobstructed coronary arteries: reply

We thank Coceani and L'Abbate for their comments on our paper.We concur that ‘pathophysiology cannot be inferred fromcoronary lumenography alone’, and this was one of thekey motivations in conducting the present study.     

Trigeminal autonomic cephalalgias. Part 3: short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing.

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a syndrome characterized by severe, strictly unilateral short-lasting (between 5 and 240 seconds) pain localized to orbital, supraorbital, and temporal areas, accompanied by ipsilateral conjunctival injection and lacrimation. It represents 1 of 3 primary headaches classified as trigeminal autonomic cephalalgias (TACs). Although its prevalence is extremely small, SUNCT patients may present at dental offices seeking relief for their pain. It is important for oral health care providers to recognize SUNCT and render an accurate diagnosis. This will avoid the pitfall of implementing unnecessary and inappropriate traditional dental treatments in hopes of alleviating this neurovascular pain. The following article is part 3 of a review on TACs and focuses on SUNCT. Aspects of SUNCT, including epidemiology, genetics, pathophysiology, clinical presentation, classification and variants, diagnosis, medical management, and dental considerations are discussed.     

Lecithin vesicles for topical delivery of diclofenac.

Skin penetration of topically applied diclofenac is important for the treatment of rheumatic diseases and actinic keratoses. We have studied the permeation of diclofenac across human cadaver epidermis in-vitro from four lecithin vesicle formulations and a few marketed semi-solid preparations. The lecithin vesicle formulations were prepared by dissolving the lipid contents (lecithin and sodium cholate) in a 1:1 mixture of methanol-chloroform, evaporating the solvents under vacuum, and hydrating the lipid layer with the drug solution in water or 10% ethanol. The vesicles were sonicated for 5 min to reduce the vesicle size and their size and Zeta potential were characterized. The cumulative amount and maximum flux of diclofenac was 69.7+/-40.3 micrograms and 4.77+/-3.16 micrograms/hcm(2) from lecithin vesicles containing sodium cholate and 10% ethanol, and is the highest of all formulations studied. The cumulative amount and mean maximum flux obtained from other formulations were in the range of 2.46+/-1.98-29.9+/-10.1 micrograms and 0.53+/-0.46-3.61+/-0.86 micrograms/hcm(2). Based on the results, lecithin vesicles of diclofenac appear to be advantageous for the topical delivery of diclofenac.