Diminished degradation of myelin basic protein by anti-sulfatide antibody and interferon-gamma in myelin from glia maturation factor-deficient mice

In this study we show the effect of anti-sulfatide (RmAb) antibodies and inflammatory cytokines, TNF-alpha and IFN-gamma in inducing myelin basic protein (MBP) degradation in myelin isolated from control wild type (WT) and glia maturation factor (GMF)-deficient (GMF-KO) mice. GMF was not detected in isolated myelin from WT and GMF-KO mice although it is present in brains of WT mice. Our results show that calcium-dependent neutral protease activity caused significantly elevated degradation of 18.5 and/or 17.5kDa isoforms of MBP in WT myelin treated with RmAb or IFN-gamma. In contrast, MBP degradation in isolated myelin from GMF-KO mice remained unaffected following treatment with RmAb, IFN-gamma, or GM-CSF. Neither the 14kDa isoform of MBP nor proteolipid protein (PLP) showed an elevated degradation compared to controls. A virtual absence of GM-CSF, TNF-alpha and IFN-gamma in GMF-KO brain compared to WT was also evident when the animals were challenged with MOG 35-55. Additionally, the myelin from GMF-KO mice showed difference in distribution of myelin oligodendrocyte glycoprotein (MOG) and beta-tubulin in a sucrose density gradient myelin-axolemmal fractions compared to WT. Taken together, our data suggests a role for GMF in the biochemical organization of myelin and thereby its effect on MBP degradation induced by RmAb and IFN-gamma.     

Conjugation to Ascorbic Acid Enhances Brain Availability of Losartan Carboxylic Acid and Protects Against Parkinsonism in Rats

Identification of renin-angiotensin system in the interplay of hypertension and neurodegeneration has paved the way for the repurposing of antihypertensive drugs against Parkinsonism. Losartan carboxylic acid (LCA), the potent AT1 blocker metabolite of losartan, suffers from poor bioavailability and brain access. Since ascorbate transporters have earlier shown enough flexibility as carriers, we have conjugated losartan carboxylic acid to ascorbic acid with the aim of achieving higher oral/brain availability. Ester of LCA and ascorbic acid (FED) was developed keeping in view the substrate specificity of ascorbate transporters. Oral/brain bioavailability was assessed using in vivo pharmacokinetic model. Effect on central nervous system (CNS) and protection against Parkinsonism was evaluated using in vivo models. FED enhanced bioavailability of LCA. The higher brain availability of LCA enabled CNS protection as evident from the increase in locomotor activity, improved motor coordination, and protection against drug-induced catatonia. In conclusion, FED offers an approach to repurpose LCA against Parkinsonism. This can encourage further investigation to simultaneously address hypertension and neurodegeneration.     

Finger pulp reconstruction with thenar flap: Aesthetic and functional outcome

Purpose: Fingertip injuries are common in industrial production activities as well as in domestic work. Loss of pulp hampers daily life activities. Functional and aesthetic aspects are important in fingertip reconstruction. The bone is usually exposed along with soft tissue loss. Therefore to reconstruct the pulp flap with adequate bulk is required. Methods: We reported a case series of 12 patients with the injury over the volar aspect of distal phalanx of the index or middle finger. In all cases, laterally based thenar flap was chosen. The flap donor site was closed primarily in most of cases, while 4 patients required skin graft. The flap was detached between 2-3 weeks. Functional assessment was done using static and dynamic 2-point discrimination and range of motion at each joint. The aesthetic outcome was assessed through questionnaire. The results were analyzed using the unpaired t-test (SPSS version 21). Results: Partial necrosis occurred in 2 cases while rest of flaps survived successfully. Static 2-point discrimination ranged from 6e10 mm, mean 8.6 mm; and dynamic 2-point discrimination ranged from 8-10 mm, mean 8.9 mm. The mean satisfaction score was (4.0 ± 0.55). Conclusion: Thenar flap is a good choice for reconstruction of the finger pulp as it provides the bulk with good functional and aesthetic outcome.     

Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction,apoptosis and inflammation in rats: Possible mechanism of nephroprotection

Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100 mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in the kidney.     

Development and validation of a questionnaire to assess socio-behavioural impact of COVID-19 on the general population

Background and aimThe aim of the study is to develop a valid and reliable tool to assess sociobehavioural changes due to COVID among the general population.MethodsThis mixed method study has two phases. Phase I for questionnaire development (literature review, focus group discussion, expert evaluation and pilot testing). Phase II for establishing construct validity via factor analysis and internal consistency via Cronbach’s ɑ by administering the questionnaire on 179 participants.ResultsA questionnaire comprising 33 questions and five domains was developed having Cronbach’s α of 0·82.ConclusionThe developed questionnaire is a concise, easy to administer and valid tool to assess socio-behavioural changes.     

Improved tuberculosis case detection through public-private partnership and laboratory-based surveillance, Kannur District, Kerala, India, 2001-2002.

BACKGROUND: Efforts to intensify global tuberculosis (TB) control are limited by difficulties in coordinating with private doctors. More than half of Indian TB patients may initially consult a private provider, but many are neither diagnosed accurately nor treated effectively. We established and evaluated a public-private partnership based on surveillance of TB detected in private laboratories and use of standardised directly observed treatment regimens. METHODS: In one district, the governmental TB control programme offered training in microscopy to all large private sector laboratories, and educated private physicians on the importance of microscopy for TB diagnosis. We reviewed records from participating private laboratories and all publicly diagnosed patients. RESULTS: Of 2328 pulmonary TB patients registered from July 2001 to December 2002, 404 (17%) were detected in the private sector. The annual new AFB-positive case notification rate increased by 21%, from 27.8/100,000 in 2000 to 33.5/100,000 in 2002. Surveillance at private laboratories found an additional 260 nonregistered AFB-positive patients. CONCLUSIONS: This public-private partnership substantially increased TB case detection and established a sustainable framework for private sector involvement in TB control. In the setting of a strong public sector programme, the combination of active surveillance of private laboratories along with physician sensitisation is a promising approach to improve TB case detection.     

Detection of abnormal proliferation in histologically 'normal' colonic biopsies using FTIR-microspectroscopy

BACKGROUND: Abnormal crypt proliferation and development in the colon has been associated with premalignant stages of colon cancer. Conventionally, molecular markers are used to detect abnormal crypt proliferation. METHODS: In the present work, feasibility studies of FTIR-MSP to distinguish between normal and abnormal crypts from colon biopsies that show normal histopathological features have been undertaken. RESULTS: The results indicate that abnormal crypts show deviations in the pattern of absorbance in the Mid IR region along the crypt height when compared with the normal crypts. The crypts could be empirically classified into three groups such as crypts having a normal absorbance pattern for all biochemical components, crypts with abnormal absorbance pattern for some biochemical components and crypts with completely abnormal absorbance pattern along the height for all or most biochemical components studied by FTIR. The utilization of FTIR-MSP is proposed for diagnosis of abnormal metabolism at the molecular level of histologically completely normal-looking crypts, especially from those biopsies that are taken from sites far away from cancer. CONCLUSIONS: This method could give rise to a reduction in false-negative results during examination of biopsies using the conventional histopathological methods. The present method may be complementary to existing methods for precise demarcation of the zone of colostomy prior to colon cancer surgery.