Warfarin-related Nephropathy.

Warfarin-related nephropathy also referred to as anticoagulant-related nephropathy (ACRN) is a type of acute kidney injury (AKI) that may be caused by excessive anticoagulation with warfarin and other anticoagulants. Despite the well-described histological entity, the clinical course and approach to ACRN in patients requiring life-long anticoagulation are however not well described in the literature. We report a 50-year-old Indian woman who was on prolonged anticoagulant therapy post-mitral valve replacement. She presented with AKI, and renal biopsy was suggestive of ACRN. Steroids were given and her creatinine levels reached within the normal range in 2 weeks. A presumptive diagnosis of ACRN should be made if a severe warfarin coagulopathy is present and if other causes of AKI have been excluded, in patients with chronic anticoagulant therapy. Renal function should be monitored regularly in patients who are on anticoagulant therapy.

NPHS2 mutation analysis and primary nephrotic syndrome in southern Indians.

AIM: Nephrotic syndrome is one of the most commonly diagnosed primary kidney diseases and its progressive forms can lead to chronic kidney disease and or end-stage renal disease. Steroid-resistant nephrotic syndrome is defined by resistance to standard steroid therapy and it remains one of the most intractable causes of kidney failure. Mutations in NPHS2, which encodes for podocin, an integral membrane protein of the glomerular epithelial cells (podocytes), represent a frequent cause of steroid-resistant nephrotic syndrome worldwide. This study was aimed at screening for known NPHS2 mutations in Indians with nephrotic syndrome. METHODS: We screened a cohort of 484 subjects from the southern Indian population for the presence of four missense mutations G92C, P118L, R138Q and D160G within the NPHS2 gene using tetra primer ARMS PCR. RESULTS: Our results revealed that these mutations were seen only among the patients (14.02%) and were absent in the controls, suggesting their disease-causing nature. Further categorization revealed that these mutations were together responsible for 18.5% of steroid-resistant cases in our study group. Conversely, the studied mutations were not found in the controls as well as in the patients with steroid-sensitive nephrotic syndrome. CONCLUSION: This is the first such report from India. More studies are warranted to establish the frequency of NPHS2 mutations in the Asian-Indian population and such analysis may help in developing mutation(s)-specific therapeutic interventions in the future.

Prevalence of Peste-des-petits-ruminant virus antibodies in cattle, buffaloes, sheep and goats in India.

The present study describes the prevalence of Peste-des-petits-ruminant virus (PPRV) antibodies in cattle, buffaloes, sheep and goats carried out during the period 2011 using the serum samples randomly collected from different villages of five states of India. A total of 1,498 serum samples [n = 605 (cattle); n = 432 (buffaloes); n = 173 (sheep); n = 288 (goats)] were collected from 52 districts in five states (Andhra Pradesh, Gujarat, Jammu and Kashmir, Maharashtra and Rajasthan) of India and were screened for PPRV-specific antibodies by using PPR monoclonal antibody-based competitive ELISA kit. Analysis of 1,498 samples indicates that an overall seroprevalence of 21.83 % with 11.07 % in cattle, 16.20 % in buffaloes, 45.66 % in sheep and 38.54 % in goats. This report presents the results of PPRV-specific antibodies in situations where the subclinical, inapparent or nonlethal or recovery of infection was suspected in cattle, buffaloes, sheep and goats. The presence of PPRV antibodies demonstrate that bovines are exposed to PPRV infection and it implies the importance of cattle and buffaloes as subclinical hosts for the virus besides widespread presence of the disease in sheep and goats. Further, the study showed that the prevalence of PPRV antibodies in apparently healthy livestock under natural situation, 21.83 % of the animals were protected from PPRV re-infection. This inturn help in the implementation of disease control strategies such as vaccination in that particular geographical area.

Structural characterization and mutational assessment of podocin - a novel drug target to nephrotic syndrome - an in silico approach.

Non-synonymous single nucleotide changes (nSNC) are coding variants that introduce amino acid changes in their corresponding proteins. They can affect protein function; they are believed to have the largest impact on human health compared with SNCs in other regions of the genome. Such a sequence alteration directly affects their structural stability through conformational changes. Presence of these conformational changes near catalytic site or active site may alter protein function and as a consequence receptor-ligand complex interactions. The present investigation includes assessment of human podocin mutations (G92C, P118L, R138Q, and D160G) on its structure. Podocin is an important glomerular integral membrane protein thought to play a key role in steroid resistant nephrotic syndrome. Podocin has a hairpin like structure with 383 amino acids, it is an integral protein homologous to stomatin, and acts as a molecular link in a stretch-sensitive system. We modeled 3D structure of podocin by means of Modeller and validated via PROCHECK to get a Ramachandran plot (88.5% in most favored region), main chain, side chain, bad contacts, gauche and pooled standard deviation. Further, a protein engineering tool Triton was used to induce mutagenesis corresponding to four variants G92C, P118L, R138Q and D160G in the wild type. Perusal of energies of wild and mutated type of podocin structures confirmed that mutated structures were thermodynamically more stable than wild type and therefore biological events favored synthesis of mutated forms of podocin than wild type. As a conclusive part, two mutations G92C (-8179.272 kJ/mol) and P118L (-8136.685 kJ/mol) are more stable and probable to take place in podocin structure over wild podocin structure (-8105.622 kJ/mol). Though there is lesser difference in mutated and wild type (approximately, 74 and 35 kJ/mol), it may play a crucial role in deciding why mutations are favored and occur at the genetic level.

Prevalence of peste des petits ruminants in goats in North-East India.

The present study describes prevalence of peste des petits ruminants (PPR) virus infection in goats in various parts of North-East (NE) India by screening of suspected serum samples collected during outbreak investigation and random samples during 2013-2014 survey. A total of 391 serum samples (318 random and 73 outbreak/suspected) were collected from 28 districts in 7 states (Meghalaya, Assam, Manipur, Nagaland, Arunachal Pradesh, Tripura and Mizoram) of NE India. Serum samples were screened for PPRV-specific antibodies by using PPR monoclonal-antibody based competitive ELISA. Analysis of 391 serum samples indicates that an overall seroprevalence of 17.90 % [CI 95 % 14.40-22.00] in goats {45.2 % in suspected [CI 95 % 34.32-56.58] and 11.63 % in random [CI 95 % 8.56-15.63] samples} in NE India. As expected prevalence was high in outbreaks vis-à-vis random samples. The random survey results (11.63 %) has specific implication in epidemiological perspectives, since it highlights the exact PPR prevalence under natural situations, where the subclinical, in apparent or nonlethal or recovery of infection was suspected in goats, as samples were collected from unvaccinated animals. It also warrants appropriate control measures against PPR in NE region to prevent spread of infection besides widespread presence of the disease in rest of India.

Foothold of NPHS2 mutations in primary nephrotic syndrome.

Glomerular podocytes are highly specialized cells with a complex cytoarchitecture. Their most prominent features are interdigitated foot processes with filtration slits in between. These are bridged by the slit diaphragm, which plays a major role in establishing the selective permeability of the glomerular filtration barrier. We searched Medline and Pubmed using the combination of keywords "NPHS2", "podocin", "steroid-resistant nephrotic syndrome," and "genetics" to identify studies describing an association between NPHS2 gene and renal disease. The highly dynamic foot processes contain an actin-based contractile apparatus comparable to that of smooth muscle cells. Mutations affecting several podocyte proteins lead to rearrangement of the cytoskeleton, disruption of the filtration barrier, and subsequent renal disease. The fact that the dynamic regulation of the podocyte cytoskeleton is vital to kidney function has led to podocytes emerging as an excellent model system for studying actin cytoskeleton dynamics in a physiological context. Injury to podocytes leads to proteinuria, a hallmark of most glomerular diseases. Recent studies have led to a considerable increase in our understanding of podocyte biology including composition and arrangement of the cytoskeleton involved in the control of ultrafiltration. Moreover, disturbances of podocyte architecture resulting in the retraction of foot processes and proteinuria appear to be a common theme in the progression of an acquired glomerular disease. In hereditary nephrotic syndromes identified over the last few years, all mutated gene products were localized in podocytes. This review integrates our recent physiological and molecular understanding of the role of podocytes during the maintenance and failure of the glomerular filtration barrier.

Effects of the d 2 dwarfing gene in pearl millet.

Dwarf varieties have had virtually no impact on the production of pearl millet, in contrast to the case of wheat, rice, and sorghum. This research compared tall and dwarf near-isogenic F1 hybrids to attempt to determine if there were deleterious effects of the d 2 dwarfing gene that might account for the lack of release/cultivation of dwarf pearl millet cultivars. Dwarf isohybrids on average yielded less than the tails, because of a smaller average seed size combined with a similar grain number per unit area. There was, however, a larger contribution of background genetic variation (pollinator, male-sterile, and interaction effects) to hybrid variation for nearly all characters measured, including seed size, than there was of the dwarfing gene. Selection of dwarf parents capable of producing hybrids with equal seed size and yield to that of tall parents should not be difficult.

Transient gene expression in electroporated Picea glauca protoplasts.

The reporter gene for chloramphenicol acetyltransferase (CAT) was introduced into white spruce (Picea glauca (Moench) Voss.) protoplasts by electroporation. CAT transient gene expression was increased by increasing the concentration of pCaMVCN plasmid and was affected by the level of the applied voltage. Highest CAT activities were obtained after electroporation with a pulse of 350V.cm(-1) having an exponential decay constant of approximately 105ms. Linearized plasmid constructs gave much higher levels of CAT activity than circular plasmid. Attempts to use the Escherichia coli ß-glucuronidase gene (ß-GUS) as a marker gene revealed very high levels of ß-GUS-like activity in electroporated protoplasts. This activity was mainly due to a small molecule and may mask successful transformation since ß-GUS-like activity increased when plasmid DNA was present during electroporation.