BIN1 in the Pursuit of Ousting the Alzheimer's Reign: Impact on Amyloid and Tau Neuropathology.

Alzheimer's disease contributes to 60-70% of all dementia cases in the general population. Belonging to the BIN1/amphiphysin/RVS167 (BAR) superfamily, the bridging integrator (BIN1) has been identified to impact two major pathological hallmarks in Alzheimer's disease (AD), i.e., amyloid beta (Aß) and tau accumulation. Aß accumulation is found to increase by BIN1 knockdown in cortical neurons in late-onset AD, due to BACE1 accumulation at enlarged early endosomes. Two BIN1 mutants, KR and PL, were identified to exhibit Aß accumulation. Furthermore, BIN1 deficiency by BIN1-related polymorphisms impairs the interaction with tau, thus elevating tau phosphorylation, altering synapse structure and tau function. Even though the precise role of BIN1 in the neuronal tissue needs further investigation, the authors aim to throw light on the potential of BIN1 and unfold its implications on tau and Aß pathology, to aid AD researchers across the globe to examine BIN1, as an appropriate target gene for disease management.

Unusual manifestations of extra-pulmonary tuberculosis: a pictorial essay.

Purpose: Tuberculosis is quite common in India. About 40% of all Indians are infected with mycobacterium tuberculosis, with 2.5 million active tuberculosis cases. Tuberculosis primarily affects the lungs, but it can affect any organ. Extra-pulmonary involvement occurs 15-20% of cases in immune-competent patients and in more than 50% in HIV patients. The most common extra-pulmonary sites are lymph nodes, pleura, abdomen, genitourinary tract, skin, joints and bones, or meninges. Case reports: In this pictorial review article we present 8 atypical cases of tuberculosis and describe their imaging features and histopathology. Conclusions: Extra-pulmonary tuberculosis can affect virtually any organ and can mimic various inflammatory and neoplastic disorders apart from other infective conditions. A strong index of suspicion is required particularly in those countries endemic to tuberculosis.

Evaluation of the Protective Effect of NMDA/Non-NMDA Receptor Antagonists Against Ethambutol Induced Retinal Toxicity Using ERG in Wistar Rats.

To study the protective effect of NMDA and non-NMDA receptor antagonists against ethambutol (EMB) induced retinal toxicity in Wistar rats using flash electroretinogram (ERG). Rats were randomized into four groups: Group-1 received vehicle. Group-2 received oral EMB (200 mg/kg/day). Group-3 and 4 were fed with oral EMB along with memantine (MEM) (1 mg/kg, ip) and trimetazidine (TMZ) (3mg/kg, ip) respectively. All treatments were continued up to 28 days. ERG was recorded at 0 and 21st day using green and white lights. Ethambutol and 2, 2' ethylene diimino dibutyric acid (EDBA) levels were quantified in rat body fluids and tissues using LC-MS/MS. A higher rate of rat mortality was observed between 21st and 28th day, 21st day considered for ERG recording among groups. Ethambutol did not cause any significant change in 'a'-wave amplitude of rat ERG but caused a predictable decrease in 'b'-wave amplitude of the rat ERG on the 21st day. Memantine treatment showed a significant (P=0.029) protection against the fall of 'b'-wave amplitude on 21st day. Interestingly, we found that plasma levels of EMB in memantine treated rats were significantly reduced when compared to the positive control group. Memantine reversed the effects of EMB on 'b'-wave of rat ERG suggests its protective role. We suggest MEM may be considered as a possible preventive treatment modality for EMB induced vision toxicity warranting further clinical investigations.

Utility of the trough plasma imatinib level monitoring at two time points in patients with the chronic myeloid leukemia-chronic phase.

INTRODUCTION: Plasma imatinib levels vary widely in patients with the chronic myeloid leukemia-chronic phase, and studies have shown improved hematological, cytogenetic, and molecular responses in patients with the higher trough imatinib levels. MATERIALS AND METHODS: We analyzed 50 consecutive patients with the chronic myeloid leukemia-chronic phase and performed plasma imatinib levels at 1 month and 12 months and correlated them with complete hematological response at 3 months and molecular response at 12 months, respectively. RESULTS: Trough plasma imatinib levels at 1 month correlated well with complete hematological response at 3 months (P = 0.007) and levels at 12 months correlated with molecular response at 12 months (P = 0.04). Compliance to imatinib also significantly correlated with imatinib levels at 1 month (P = 0.0008) and imatinib levels at 12 months (P = 0.0002). CONCLUSION: Plasma imatinib levels may be of benefit in patients not achieving desired response at defined time intervals. The plasma level monitoring also helps in the assessment of drug compliance.

Sporadic bilateral synchronous multicentric papillary renal cell carcinoma masquerading as bilateral multifocal pyelonephritis.

Pyelonephritis is defined as an inflammation of the kidney and renal pelvis. The diagnosis is usually clinical. Acute multifocal bacterial nephritis is a rare form of pyelonephritis that is more severe and sepsis is more common. We report a patient who presented with fever and right-sided abdominal pain associated with right flank tenderness, suggesting right acute pyelonephritis. Bilateral multifocal pyelonephritis was diagnosed on ultrasonography, radionuclide renal scintigraphy and computed tomography. However, owing to non-resolution of symptoms, a biopsy was performed, which showed bilateral papillary renal cell carcinoma (PRCC). PRCC is known to exhibit multicentricity. To our knowledge, a case of bilateral multicentric PRCC masquerading as bilateral multifocal pyelonephritis has not been reported in the English literature. This case highlights the need to be vigilant while treating patients with focal lesions of the kidney as an inflammatory condition lest a malignancy should be missed.

Evaluation of calcium dobesilate for its anti-cataract potential in experimental animal models.

The present study evaluated the protective action of calcium dobesilate (CDO) in various experimental models of cataract. CDO was studied in hydrocortisone-induced cataract in developing chick embryos and selenite-induced cataract in pups. CDO anti-cataract activity was also evaluated after oral and topical application as eye drops in galactose (30%) fed rats. This study was further extended to evaluate the intraocular penetration of a single dose of 1% CDO (50 microL) in rabbits. CDO exhibited significant protection against cataract in experimental models and considerable penetration after single topical application. Anti-cataract activity may be due to its antioxidant as well as aldose reductase inhibitor properties. Further studies are in progress to evaluate its clinical efficacy in diabetic cataract.

Acute aortic dissection--De Bakey Type I and Stanford A.

We report a rare case of aortic dissection which fits into De Bakey Type I and Stanford A, presented with severe tearing chest pain, paraplegia, stupor, hypotension, and syncope. Echocardiography showed dissection involving aortic root. MRI showed aortic dissection involving ascending, arch and descending aorta. Patient was managed conservatively and he died within 12 hours after the admission.

Rapid alcohol determination in plasma and urine by column liquid chromatography with biosensor detection.

An enzyme based amperometric biosensor used as a selective and sensitive detection unit in column liquid chromatography for the determination of ethanol and methanol in biological fluids such as plasma and urine is described. The reagentless enzyme electrode is based on the co-immobilisation of alcohol oxidase and horseradish peroxidase in carbon paste. The selectivity of the biosensor was found to vary when four various alcohol oxidase enzyme preparations from Candida boidinii, Pichia pastoris, and Hansenula polymorpha were used in the biosensors described. High sensitivity could be obtained for a number of alcohols, organic acids, and aldehydes. Optimisation regarding the sensitivity and selectivity of the four alcohol oxidase co-immobilised biosensors are outlined. A fast and reliable liquid chromatographic separation system with a PLRP-S polymer based separation column used with a phosphate buffer as the mobile phase was optimised using the best biosensor which was based on alcohol oxidase from P. pastoris and which showed the highest turnover rate for alcohols, as the detector for the determination of ethanol and methanol in human urine and plasma samples. The selectivity and stability of the biosensor were retained by working at an applied potential of -50 mV versus Ag/AgCl, the optimal operational potential, and by the casting of a protective membrane on the electrode surface. High selectivity of the enzyme electrode was also found towards other easily oxidisable interfering species normally present in biological fluids. It was found that stable and reliable determinations of ethanol and methanol in plasma and urine could be performed with only a simple dilution and centrifugation step prior to injection into the liquid chromatographic system. An analysis time of 4 min was required for the assay, with a sample throughput of 13 samples h(-1).