Effect of Withania somnifera (L.) Dunal aqueous root extract on reinstatement using conditioned place preference and brain GABA and dopamine levels in alcohol dependent animals.

ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera (L.) Dunal (WS), a known'Rasayana' (rejuvenating agent) as per Ayurveda is prescribed to promote health, to increase longevity and to hasten recovery in disease convalescent stages. WS has demonstrated protective effect on alcohol dependence and withdrawal anxiety in previous experimental studies. AIM OF THE STUDY: To evaluate effect of WS on conditioned place behavioral paradigm (model of relapse) and on GABA and dopamine levels in critical brain areas in alcohol dependent animals. METHODOLOGY: Following Animal Ethics Committee permission, the mice (n = 24) were divided into the following study groups for experiment 1: 1 -distilled water (vehicle control), 2 -WS and 3 -Naltrexone. They were conditioned on conditioned place preference (CPP) using alcohol (2 gm/kg)/saline (1 ml) administered intraperitoneally for 8 days. WS and Naltrexone were administered during the period of extinction (6-8 days). Effect of WS (650 mg/kg) on reinstating behaviour of mice (time spent in alcohol paired compartment) primed with alcohol injection was noted. In experiment 2, effect of WS (450 mg/kg/) on GABA and dopamine levels in the midbrain, striatum and cortex (ng/gm) were measured in alcohol dependent rats (n = 24) following the first phase of standardisation assay (n = 36). The rats were made alcohol dependent for 15 days (intermittent access model) and WS was administered concurrently. GABA and dopamine levels were measured on Day 16. RESULTS: WS group showed decrease in time spent in alcohol paired compartment alike Naltrexone and it differed significantly compared to the distilled water control group (p < 0.05) Alcohol-dependent rats showed significant decrease in GABA and increase in dopamine levels vs distilled water in the midbrain, striatum and cortex. WS and Naltrexone administration showed rise in GABA and fall in dopamine in all the isolated brain parts in the respective groups (p < 0.05 vs alcohol treated group). CONCLUSION: Withania somnifera protected animals from relapse and showed beneficial effects on the brain neurotransmitters involved in alcohol dependence. The study provides substantial evidence for its potential application in alcohol use disorder.

Genome-wide gene expression pattern underlying differential host response to high or low pathogenic H5N1 avian influenza virus in ducks.

The differences in the influenza viral pathogenesis observed between different pathogenic strains are associated with distinct properties of virus strains and the host immune responses. In order to determine the differences in the duck immune response against two different pathogenic strains, we studied genome-wide host immune gene response of ducks infected with A/duck/India/02CA10/2011 and A/duck/Tripura/103597/2008 H5N1 viruses using custom-designed microarray. A/duck/India/02CA10/2011 is highly pathogenic virus (HP) to ducks, whereas A/duck/Tripura/103597/2008 is a low pathogenic (LP) virus strain. Comparative lung tissue transcriptome analysis of differentially expressed genes revealed that 686 genes were commonly expressed, 880 and 1556 genes are expressed uniquely to infection with HP and LP virus, respectively. The up-regulation of chemokines (CCL4 and CXCR4) and IFN-stimulated genes (IFITM2, STAT3, TGFB1 and TGFB3) was observed in the lung tissues of ducks infected with HP virus. The up-regulation of other immune genes (IL17, OAS, SOCS3, MHC I and MHC II) was observed in both infection conditions. The expression of important antiviral immune genes MX, IFIT5, IFITM5, ISG12, ß-defensins, RSAD2, EIF2AK2, TRIM23 and SLC16A3 was observed in LP virus infection, but not in HP virus infection. Several immune-related gene ontology terms and pathways activated by both the viruses were qualitatively similar but quantitatively different. Based on these findings, the differences in the host immune response might explain a part of the difference observed in the viral pathogenesis of high and low pathogenic influenza strains in ducks.

IPS-1 differentially induces TRAIL, BCL2, BIRC3 and PRKCE in type I interferons-dependent and -independent anticancer activity.

RIG-I-like receptors are the key cytosolic sensors for RNA viruses and induce the production of type I interferons (IFN) and pro-inflammatory cytokines through a sole adaptor IFN-ß promoter stimulator-1 (IPS-1) (also known as Cardif, MAVS and VISA) in antiviral innate immunity. These sensors also have a pivotal role in anticancer activity through induction of apoptosis. However, the mechanism for their anticancer activity is poorly understood. Here, we show that anticancer vaccine adjuvant, PolyIC (primarily sensed by MDA5) and the oncolytic virus, Newcastle disease virus (NDV) (sensed by RIG-I), induce anticancer activity. The ectopic expression of IPS-1 into type I IFN-responsive and non-responsive cancer cells induces anticancer activity. PolyIC transfection and NDV infection upregulate pro-apoptotic gene TRAIL and downregulate the anti-apoptotic genes BCL2, BIRC3 and PRKCE. Furthermore, stable knockdown of IPS-1, IRF3 or IRF7 in IFN-non-responsive cancer cells show reduced anticancer activity by suppressing apoptosis via TRAIL and anti-apoptotic genes. Collectively, our study shows that IPS-1 induces anticancer activity through upregulation of pro-apoptotic gene TRAIL and downregulation of the anti-apoptotic genes BCL2, BIRC3 and PRKCE via IRF3 and IRF7 in type I IFN-dependent and -independent manners.

Small interfering RNAs inhibit infectious bursal disease virus replication in Vero cells.

Small interfering RNA (siRNA) molecules are considered to be a promising antiviral therapeutics. This study was performed to analyze the application of siRNA against infectious bursal disease virus (IBDV) replication. Two siRNAs were designed to target common coding sequences of four IBDV proteins. Corresponding vectors were constructed to express anti-IBDV short hairpin RNAs (shRNA) that were tested for their antiviral effect in Vero cells. The results showed that expressed shRNA inhibited the virus replication to a significant extent (92%) as determined by the virus titration in cell culture. This outcome demonstrated the effectiveness of RNA interference (RNAi) based mechanism against the IBDV in vitro.

Inhibition of Bovine herpesvirus multiplication in MDBK cells by small interfering RNAs.

Small interfering RNA (siRNA) mediated gene silencing is a promising approach in antiviral therapy. To investigate the antiviral effects of siRNAs on Bovine herpesvirus 1 (BoHV-1) multiplication, we designed and in vitro synthesized two siRNAs (siRNA-1 and siRNA-2) targeting the UL25 gene that is essential for BHV-1 multiplication. siRNA-1 and siRNA-2 inhibited the BoHV-1 multiplication in MDBK cells to a different extent, namely by 11% and 40%, respectively, as demonstrated by virus titers (TCID(50)/ml) determined in cell culture. This indicates that, in general, siRNAs can inhibit BHV-1 multiplication in vitro and could be used also against a BHV-1 infection in vivo following optimization of their application.

Paradoxical cerebral arterial gas embolism: Computed tomography findings.

Computed tomography scan findings are described in cerebral arterial gas embolism in two patients with right to left intracardiac shunts by accidental injection of air during intravenous therapy. Although imaging may not be necessary to diagnose the condition, the patient may be referred to CT scan as a case of stroke. Cerebral arterial gas embolism should be considered in the differential diagnosis of stroke, particularly in case of right-to-left shunts. CT findings described are classical and diagnostic of the condition.

The CT appearances of gallbladder perforation.

Perforation of the gallbladder is an uncommon complication of acute cholecystitis that is associated with relatively high mortality. Symptoms and clinical signs can be indistinguishable from those of uncomplicated acute cholecystitis, leading to delayed diagnosis. We reviewed the clinical and imaging findings in 17 patients with gallbladder perforation confirmed at surgery.

Blood-fluid levels in the brain.

17 cases reviewed prospectively over a period of 4 months highlight the varied appearance of blood-fluid levels in intracranial cystic lesions of different aetiologies; a finding which has not featured significantly in the medical literature. Four types of intracranial cysts demonstrating blood-fluid levels have been categorised according to the nature of the pathology, i.e. primary neoplasms of the brain, metastatic deposits to the brain in cases of extraneural malignancies, lesions of vascular aetiology and intraparenchymal bleeds secondary to trauma. The group of four primary intracranial neoplasms lists an oligodendroglioma, a recurrent tumour in a case of Von Hippel-Lindau syndrome, a Grade 3 astrocytoma and an acoustic schwannoma. Four cases of metastatic deposits to the brain were each secondary to primary malignant neoplasms of the breast, liver, ovary and lung. Of seven cases of a vascular aetiology, three resulted from arterial infarction, two from hypertension and one each from venous infarction and following anticoagulant therapy. Intracranial cysts within tumours have been postulated to occur secondary to a breakdown of the blood-brain barrier (BBB) rather than as a result of tumoural degeneration, as was thought probable earlier.

Giant renal capsular leiomyoma: study of two cases.

Leiomyomas of the renal parenchyma and of the capsule are rare. These tumours are normally small asymptomatic and often detected incidentally. Large renal leiomyomas can present with pain or as an abdominal mass, but they are rare. The imaging features of these tumours have been poorly described in the literature. A radiological distinction from other renal neoplasms is often difficult to make owing to the similarity of imaging findings. We report two patients with renal leiomyomas who presented with pain and an abdominal mass. Both patients underwent nephrectomy and histological evaluation confirmed the diagnosis of leiomyoma.

Echinococcosis of the rib with epidural extension: a rare cause of paraplegia.

Skeletal echinococcosis is a relatively rare entity and that of the rib is exceptional. Less than 50 cases of costal echinococcosis have been reported in the literature so far. Accurate pre-operative diagnosis aids in appropriate management and helps to eradicate the disease. This also prevents the dissemination of parasite and further complications. We report a case of echinococcosis of the rib with epidural extension in a young adult who presented with paraparesis and back pain. His laboratory investigations were within normal limits. Plain radiographs of the dorsal spine, CT scan of thorax and MRI of dorsal spine were performed. The imaging features were suggestive of echinococcosis involving the rib with epidural extension. The cyst was completely resected. Histopathology of the resected specimen confirmed the diagnosis of echinococcosis.

Imaging features and guided drainage in emphysematous pyelonephritis: a study of 11 cases.

AIM: The purpose of the present study is to evaluate the role of image-guided drainage in emphysematous pyelonephritis (EPN). MATERIALS AND METHODS: We reviewed 11 patients with EPN treated either by ultrasonography (three patients) or computed tomography (CT)-guided drainage (eight patients). There were eight male and three female patients in our study with ages ranging from 24 to 75 years, mean 56.3 years. All the patients underwent plain radiography, ultrasonography and plain CT of the abdomen. Contrast-enhanced CT was performed in seven patients. RESULTS: Seven of 11 patients, were successfully treated with per cutaneous drainage. One patient died within 24 h (case 2), due to septicaemia. Three patients subsequently required nephrectomy. Replacement of the drainage catheter was required in one patient. The catheter was kept in situ, for an average of 17 days. The catheter drained pus and gas in all patients. The quantity of pus ranged from 300 to 2000 cm(3). All 10 patients improved symptomatically within 24 h of drainage, with improved urine output and serum creatinine levels within 48 h. CONCLUSION: CT-guided drainage of EPN has established itself as a safe, quick and life-saving palliative treatment of choice as opposed to conventional emergency nephrectomy. Excluding the patient who died, the success rate of our study was 70%.

Anti-rheumatic formulations from ayurveda.

Rheumatic disorders like Amavata, Sandhivata and Vatarakta are elaborately described in ayurvedic literature. Preliminary survey of literature shows that about 247 formulations are recommended for these rheumatic disorders. These formulations generally include guggulu compounds, compounds of plant powders, decoctions, medicated ghees, oils, electuaries etc. Therapeutic potential of ayurvedic concepts and a brief review of Ayurvedic formulations are also discussed.