Specific downregulation and mistargeting of the lipid raft-associated protein MAL in a glycolipid storage disorder

Metachromatic leukodystrophy (MLD) is a lysosomal lipid storage disease caused by arylsulfatase A deficiency. In MLD patients the sphingolipid sulfatide increasingly accumulates leading to progressive demyelination. We have analysed arylsulfatase A-deficient mice, a MLD mouse model, and we show that accumulation of sulfatide is not restricted to the lysosomal compartment but also occurs in myelin itself. Although, this sulfatide storage did not affect the overall composition of most myelin proteins, it specifically caused a severe reduction of MAL. This demonstrates a regulatory link between sulfatide accumulation and MAL expression and indicates the existence of regulatory mechanisms between lipid and myelin protein synthesis in oligodendrocytes. In addition, in cultured renal epithelial cells, sulfatide accumulation diverts MAL to the late endosomal/lysosomal compartment and thus also affects the intracellular distribution of MAL. The specific reduction and mistargeting of MAL protein as a reaction to sulfatide overload may contribute to the pathogenic mechanisms in metachromatic leukodystrophy.     

Prevalence and distribution of peste des petits ruminants virus infection in small ruminants in India

Peste des petits ruminants (PPR) is an acute febrile viral disease of goats and sheep characterised by mucopurulent nasal and ocular discharges, necrotising and erosive stomatitis, enteritis and pneumonia. The disease is endemic in India and causes large economic losses each year due to the high rates of mortality and morbidity in infected sheep and goats. The present study reports observations from 58 laboratory confirmed outbreaks of PPR and provides details of the prevalence of antibodies to PPR virus (PPRV) in 4,407 serum samples of small ruminants. Most of the clinical specimens used for the study originated from the northern and central parts of India. Serum samples used for the detection of antibodies to PPRV were derived from a greater number of regions within the country, however, these samples may not be a true representation of the target population (unvaccinated sheep and goats over 3 months old). Indigenously developed monoclonal antibody-based diagnostic kits were used for the detection of PPRV antigen (sandwich enzyme-linked immunosorbent assay [ELISA]) and antibody (competitive ELISA). Findings suggested that the disease outbreaks were more severe in goats than sheep and that the frequency of disease outbreaks was greater between the months of March and June (51.7%) as compared to other periods of the year. Based on the screening of the 4,407 sera samples, the antibody prevalence of PPRV in small ruminants in India was 33% (95% confidence interval: 32.3% to 33.7%). The prevalence of antibodies to PPRV was noted to differ between species (i.e. sheep versus goats), age groups and geographical regions. A greater proportion of the sheep (36.3%) versus the goat (32.4%) population was infected with PPRV. The distribution and prevalence of antibodies to PPRV among various age groups of animals indicated that goats were exposed at an earlier age than the sheep, suggesting that goats may be more susceptible to infection with PPRV. A greater number of positive cases were observed in the southern and southwestern part of the country (30%-60%) as compared to northern India (10%-30%). These findings may be correlated with variations in the sheep and goat husbandry practices within different geographic regions, the topography of different states and the socio-economic status of individual Indian farmers.     

Internet application to tele-audiology--"nothin' but net"

The Telehealth program at East Carolina University has developed a system for real-time assessment of auditory thresholds using computer driven control of a remote audiometer via the Internet. The present study used 45 adult participants in a double-blind study of 2 different systems: a conventional audiometer and an audiometer operated remotely via the Internet. The audiometric thresholds assessed by these 2 systems varied by no more than 1.3 dB for air conduction and 1.2 dB for bone conduction. The results demonstrated the feasibility of this new "telehearing" audiometric system. With the rapid development of Internet-based applications, telehealth has the potential to provide important healthcare coverage for rural areas where specialized audiological services are lacking.     

Spinal compression caused by multiple arachnoidal cyst

A 14-year-old boy presented with subacute onset of paraparesis. The spinal compression was due to multiple giant sized spinal arachnoid cysts. Postoperatively the patient recovered completely.     

Antiinflammatory, Analgesic and Antipyretic Activity of Certain Thiazolidinones

The thiazolidin-4-one derivatives and the corresponding spiro compounds were synthesized from sulphanilamide and were evaluated for anti-inflammatory and analgesic activity in acute and sub acute models. Compounds were also evaluated for antipyretic and cyclooxygenase enzyme inhibitory activity. All the compounds showed significant antiinflammatory, analgesic and antipyretic activity at 100 mg/kg in all the models. The compounds B1, B2, B5, B6, and B8 showed maximum inhibition of COX-2 activity without inhibiting the COX-1 activity. The nimesulide was used as standard drug for comparison. The substitution at R, R₁ and R₂ with the functional groups Cl, OCH₃, NO₂ and OH in the aromatic ring resulted in increased activity as compared to unsubstituted thiazolidin-4-ones. However the substitution at R₃ with spiro group did not improve the activity. The study suggests that COX-2 binding site may not be a rigid structure but might adopt to various related molecules.     

Thyroid autoantibodies.

Although assays to detect thyroid autoantibodies have been available for more than 40 years, their place in the clinical management of thyroid disease has remained controversial; however, novel automated detection techniques using recombinant antigens are increasing the sensitivity and specificity of the assays, particularly for antibodies to the TSH receptor. In addition, new antigenic targets have been defined including the sodium-iodide symporter and four eye muscle proteins targeted in Graves' ophthalmopathy. This article summarizes the immunobiology, assay methodology and prevalence in thyroid diseases of each of the major thyroid autoantibodies before discussing the clinical indications for their use in thyroid diseases.     

Therapeutic effect of <Emphasis Type="Italic">Saraca asoca</Emphasis> (Roxb.) Wilde on lysosomal enzymes and collagen metabolism in adjuvant induced arthritis

Rheumatoid arthritis is a chronic, progressive and systemic inflammatory disorder mainly affecting the synovial joints. In the present study, we evaluated the anti-arthritic effect of the methanol extract of Saraca asoca (Roxb.) Wilde., (Fabaceae) on adjuvant induced arthritis by assessing paw swelling, body weight, the levels of lysosomal enzymes, protein bound carbohydrates, serum cytokines, urinary collagen and histopathology of joints. It was found that S. asoca methanol extract at doses of 50, 100 and 200 mg/kg reduced the paw thickness and elevated the mean body weight of arthritic rats. The treatment of S. asoca showed a significant reduction in the levels of both plasma and liver lysosomal enzymes. The protein bound carbohydrates and urinary collagen contents were also decreased at a significant level by the treatment of S. asoca methanol extract. The histopathological study of the joints showed the anti-arthritic property of S. asoca which nearly normalized the histological architecture of the joints. Further, we established the anti-arthritic activity of S. asoca methanol extract by measuring the levels of cytokines in both arthritic and treated rats. The treatment of S. asoca reduced the levels of pro-inflammatory cytokines. In conclusion, S. asoca methanol extract was capable of ameliorating the conditions of arthritis in adjuvant induced arthritic rats.     

Characterization of human immunodeficiency virus (HIV1C) variants in peripheral blood mononuclear cells and spermatozoa

The presence of distinct viral variants in different cells and secretions of the same person influences the transmission of HIV as well as the response to the host defense and to therapy. Sperm-associated virus is also a risk factor for sexual transmission of HIV. Characterization of the C2-V3 region of HIV1C env gene by the Heteroduplex Mobility Assay (HMA) and sequencing demonstrated the presence of distinct variants in the peripheral blood mononuclear cells (PBMCs) and the sperm of the same individual (n = 6). The translated amino acid sequences of HIV variants in the PBMCs of all the study participants (n = 12) and spermatozoa of the six participants characterized showed the presence of distinct variants with different numbers of N-linked glycosylation (NLG) sites. Infectivity of PBMCs of these persons by co-culture with PBMCs from healthy individuals as detected by the p24 levels in the culture supernatant did not show a correlation with the blood plasma viral load. Interestingly, the infectivity of the sperm samples from four of the five individuals showed positive correlation with the viral load in seminal plasma. The study suggests the presence of distinct viral variants in the sperm and PBMCs of the same person with differential infectivity, and the NLG sites may be associated with the affinity of HIV to receptor/co-receptor usages as well as affinity toward neutralizing antibodies which may influence the risk of sperm associated virus in sexual transmission of HIV and transmit the virus further to distal cells.     

Limb conservation in extremity soft tissue sarcomas with vascular involvement

Background:

The major neurovascular involvement and large primary tumors are indication of amputation. The present study is an attempt to explore the feasibility of a limb salvage surgery in extremity sarcoma cases with major vessel involvement. Oncological outcomes and surgery-related morbidities are compared with those reported in literature.

Materials and Methods:

A retrospective review of all limb salvage surgeries done in our department between 2005 and 2008 was done and four cases of extremity sarcoma of lower limb involving femoral vessels analyzed. Interpretation of data from these cases, along with review of literature, is done.

Results:

In all these cases a wide monobloc excision was done adhering to oncological principles. This required resection of superficial femoral artery alone in two cases, resection of superficial femoral artery along with common femoral vein and femoral nerve in another, and of common femoral vein alone in yet another. Reconstruction was done in all these cases with reversed long saphenous vein graft. Histopathology of resected margins was free of tumor in all the four patients. One patient developed local recurrence and one developed distant metastsis. Two were disease free for one year with good functional limb, one has been disease-free for three years and another was disease-free at two years, after which he defaulted further follow-up. One patient developed arterial blowout which required ligation of common femoral artery which resulted in gangrene of the limb. He underwent amputation.

Conclusion:

Major neurovascular involvement in extremity sarcoma is not considered a contraindication for limb salvage surgery. Review of literature also supports our view. Post-operative wound related complications are more in this group of patients. However, long term functional outcome is good. Literature suggests a good long term local control after vascular resection and reconstruction.