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The nucleotide sequences of the phosphoprotein (P) gone of peste des petits ruminants (PPRV) vaccine virus (PPRV Sungri/96) belongs to Asian lineage have been determined and the deduced amino acid sequences were compared with another vaccine strain PPRV/Nigeria75/l and with those of the other morbilliviruses. The 1652 nucleotides of the P gone encode a phosphoprotein of 509 amino acid residues (from nucleotide numbers 60 to 1587), which is 91% identical to that of PPRV/Nigeria75/l. The C protein consists of 177 amino acid residues and is 91% identical with that of PPRV/Nigeria75/l. The conserved mRNA editing site (5′TTAAAAGGGCACAG) was present at positions 742-756 in the P gone, which is conserved in all other morbilliviruses, The CTT trinucleotide sequence is present at the N/P and P/M intergenic region, which is totally conserved in morbilliviruses. This will be the third sequence for the P gone of PPRV since that of the vaccine strain and a wild-type Turkish isolate has been published already. [ABSTRACT FROM AUTHOR]

Polyphenols can exert both, antioxidant and pro-oxidant properties, depending on cell types as well as their concentrations. Hence, it was of interest to examine if the naturally occurring resveratrol analog, trans-4,4'-dihydroxystilbene (DHS) also exert both these activities in a biphasic or cell-specific manner. In this study, we established the cytoprotective action of DHS against hydrogen peroxide (H2O2)-induced apoptotic death of the PC12 cells. DHS reduced mitochondrial membrane permeabilization and deactivated reactive oxygen species (ROS)-mediated caspase-3 activation in the H2O2-treated PC12 cells. However, it induced apoptosis in the human neuroblastoma SHSY-5Y cell line by destabilizing mitochondrial membrane, augmenting ROS and activating caspapse-3. DHS showed better activity than resveratrol in both the chosen models.

Oxidative stress occurs due to delicate imbalance between pro-oxidant and anti oxidant forces in our system. It has been found to be associated with many morbidities but its association with obesity and insulin resistance is still controversial. Here in our study we examined 167 patients of recent onset type 2 diabetes mellitus and 60 age sex matched non-diabetic control. Body Mass Index (BMI), abdominal circumference, fasting blood glucose, serum insulin and plasma Malondealdehyde (MDA, marker for oxidative stress) were measured in them. On the basis of BMI, subjects were divided into obese (BMI≥25) and non obese (BMI<25) groups. Insulin resistance scores were calculated by Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) method. Physical parameters (BMI, abdominal circumference) as well as levels of insulin and MDA were found to be significantly higher in subjects with diabetes than their non diabetic controls. The said parameters also showed significant difference in obese and non-obese sub groups. Insulin resistance score showed positive correlation with BMI, abdominal circumference, and plasma MDA, strength of association being highest with abdominal circumference. Plasma MDA was found to have positive correlation with physical parameters. Study concludes that, obesity mainly central type may predispose to insulin resistance and oxidative stress may be a crucial factor in its pathogenesis. Thus, oxidative stress may be the connecting link between obesity and type 2 diabetes mellitus, two on going global epidemics.

Peste des petits ruminants, a viral disease of small ruminants, the control of which is important for poverty alleviation and to ensure livelihood security in Asia, Middle East and Africa. In recognition of these issues, we developed and applied vaccine and diagnostics to demonstrate effective control of PPR during preceding 6 years in a sub-population of small ruminants in India. Two south Indian states, namely Andhra Pradesh and Karnataka, strongly indicated possibility of PPR control with more than 90 % reduction in number of reported outbreaks of PPR, mostly through mass vaccination. Similarly, the situation at the national level also demonstrated a decline of more than 75 % in the number of reported outbreaks. Sharing these experiences may motivate other countries for similar initiatives leading to progressive control of PPR, which is in line with the initiatives of the organizations like FAO/OIE and the recent platforms on global PPR research alliance.

A 20-year-old woman presented with multiple painless nodular swellings on the skin of the extremities and face, without any systemic symptoms. Biopsy with immunohistochemistry revealed a diagnosis of precursor B-cell lymphoblastic lymphoma. There was no extracutaneous site of involvement. The patient denied chemotherapy and was subsequently lost to follow-up. She presented with symptomatic disseminated disease 18 months later and rapidly succumbed to her illness.

This communication reports about heat shock protein response after arsenic exposure in broiler chickens in vivo and in vitro both. Splenocytes harvested in presence of sodium arsenite expressed Heat shock protein 70 (HSP 70) which could be identified on the basis of relative migration pattern and western blot analysis. Serum levels of HSP 70 in broiler chicken also increased after continuous feeding of sodium arsenite in drinking water. This particular observation may be attributed towards systematic inflammation, oxidative stress and hepatocellular injury. In vitro relative quantification of transcription level of HSP 70 revealed that splenocytes harvested in presence of sodium arsenite expressed (final concentration 3 and 7 μM/ml) more HSP 70 in comparison to cells harvested without sodium arsenite and the values were statistically significant (P < 0.001) when compared to untreated control. Collectively this result indicated that, HSP 70 level increased both in vivo and in vitro trials and may be used as potential molecular and toxicological biomarker.

Mitochondrial diseases are extremely heterogeneous multisystem disorders predominantly affecting tissues or organs with high oxygen consumption like skeletal muscles, brain, endocrine glands, myocardium, eyes, ears, intestines, liver, kidneys, and bone marrow. Although various clinical syndromes have been described, they frequently overlap and there is no diagnostic gold standard to identify all. It is difficult to chart the future of an affected individual as also to predict the response to treatment which is mostly supportive and symptomatic. The rapidly increasing understanding of the pathophysiologic background of mitochondrial disorders may facilitate diagnostic approach and open perspectives to curative therapies. With the coming of age for mitochondrial medicine, it is now appropriate that physicians keep themselves well-acquainted with the recent developments in this expanding field of biomedical research.

A family with hereditary (familial) hypoparathyroidism is reported where three of the total four siblings were affected and each presented with different manifestation-one brother with refractory epilepsy since early childhood, another brother with unilateral extrapyramidal features in adult life, and their only sister having recurrent attacks of tingling and numbness due to hypocalcemia since 12 years of age.

The role of the ariginine-metabolism in the healing action of the methanol extract of Myristica malabarica (rampatri) (RM) and omeprazole (Omez) against indomethacin-induced stomach ulceration in mouse was investigated. Indomethacin (18 mg/kg) was found to induce maximum stomach ulceration in Swiss albino mice on the 3rd day of its administration, which was associated with reduced arginase activity (38.5%, p < 0.05), eNOS expression, along with increased iNOS expression, total NOS activity (5.37 fold, p < 0.001), NO generation (55.1%, p < 0.01), and ratio of pro-/anti-inflammatory cytokines. Besides providing comparable healing as Omez (3 mg/kg × 3 d), RM (40 mg/kg × 3 d, p.o.) shifted the iNOS/NO axis to the arginase/polyamine axis as revealed from the increased arginase activity (59.5%, p < 0.01), eNOS expression, and reduced iNOS expression, total NOS activity (73%, p < 0.001), and NO level (49.8%, p < 0.01). These could be attributed to a favourable anti/pro inflammatory cytokines ratio, generated by RM. The healing by Omez was however, not significantly associated with those parameters.

Arteriovenous malformations of the lung are relatively uncommon lesions with varied clinical presentation. Nearly half of these are associated with Osler-Rendu-Weber disease. Magnetic resonance angiography is an accurate and non-invasive diagnostic modality. We report a case of a 56-year-old male who had massive haemothorax due to rupture of a pulmonary arteriovenous malformation arising from the right interlobar artery.

Peste des petits ruminants (PPR) is a highly contagious and economically important viral disease of goats and sheep. A homologous Vero cell-based attenuated PPR vaccine developed in our laboratory and used extensively throughout the country, is available for control of PPR. The presently used quality control test, titration in Vero cells for PPR virus titre in vaccine batches, takes at least 6-8days to determine the quality and dose of vaccine. In this study, 74 freeze-dried PPR vaccine batches were tested simultaneously by both virus titration and PPR sandwich ELISA (S-ELISA) to correlate the titre of the vaccine virus with reactivity in S-ELISA. It was found that the vaccine batches with titre more than 10(3)TCID(50)/ml gave positive results in S-ELISA and correlated well with the virus titre of the freeze-dried vaccines. The correlation coefficient between the virus titration and S-ELISA reactivity was estimated as 0.96, indicating a high correlation between the two parameters based on 74 batches of freeze-dried PPR vaccine. The vaccine batches with titres of 3.0, 4.3, 4.5, 5.0, 6.5 and 7.0 had shown a positive reaction when tested in two-fold dilutions in S-ELISA at 1, 5, 6, 7, 8 and 9log2 titres, respectively. The test vaccine batches were found to be negative in S-ELISA when the titre of the vaccine was less than 10(3)TCID50/ml, suggesting that the vaccine could not be passed for field use. It is concluded that S-ELISA could be a preliminary tool useful for the quality control of PPR vaccine as it is rapid and easy to perform when compared to virus titration.

Aim: To evaluate the protective activity of allylpyrocatechol (APC), the major antioxidant constituent of Piper betel, against the indomethacin-induced stomach ulceration in the rat model and correlates with its antioxidative and mucin protecting properties., Methods: Male Sprague-Dawley rats were divided into five groups. Normal control rats (group I) were given the vehicle oral dose of gum acacia in distilled water (1 mL per rat); ulcerated control and treated rats (groups II-V) were given a single dose of indomethacin (30 mg/kg body wt.); group II rats were sacrificed 4 h after indomethacin administration; groups III-V rats were given the vehicle (1 mL per rat) or APC (2 mg/kg body wt.) or misoprostol (1.43 mug/kg body wt.) once daily by oral intubation for 7 d starting from 4 h after the indomethacin administration. After 7 d, the stomach tissues were excised for histological examination and biochemical analysis., Results: Treatment with APC (2 mg/kg body wt per day) and misoprostol (1.43 mug/kg body wt per day) for 7 d could effectively heal the stomach ulceration as revealed from the ulcer index and histopathological studies. Compared to the zero day ulcerated group, treatment with APC and misoprostol reduced the ulcer index by 93.4% and 85.4% respectively (P < 0.05). Both APC and misoprostol accelerated ulcer healing observed in natural recovery (P < 0.05), their respective healing capacities not being significantly different. The healing capacities of APC and misoprostol could be attributed to their antioxidant activity as well as the ability to enhance the mucin content of the gastric tissues. Compared to the ulcerated untreated rats, those treated with APC and misoprostol showed near normal MDA levels, while the protein levels were 86% and 78% of the normal value respectively (P < 0.05). Likewise, both APC and misoprostol increased the SOD, catalase, and mucin levels significantly (P < 0.05), the effect of APC being better., Conclusion: APC can protect indomethacin-induced gastric ulceration due to its antioxidative and mucin protecting properties.

Primary lymphoma of the duodenum presenting with obstructive jaundice is a rare entity. We report a case of primary non-Hodgkin's lymphoma of the duodenum producing obstructive jaundice in a middle aged lady, where the concentric thickening of the duodenal wall also gave rise to symptomatic partial high small bowel obstruction in due course. Guided aspiration and flowcytometry established a diagnosis of diffuse large B-cell lymphoma.

The complete nucleotide sequence of the nucleocapsid (N) protein of the peste-des-petits ruminants vaccine virus (PPRV Sungri/96) belonging to the Asian lineage was determined. The gene was 1692 nucleotides in length and encoded a polypeptide of 525 amino acids. The PPRV Sungri/96 N gene has a nucleotide homology of 92% for PPRV Nigeria 75/1 to 55.5% for canine distemper virus. At amino acid level the homology was 94.1% with PPRV Nigeria 75/1, while with other morbilliviruses, PPRV Sungri/96 had only 71.4-64.9% amino acid identity. The phosphorylation prediction reveals eight conserved sites across morbilliviruses, whereas in the C-terminal portion of the protein the sites are not conserved. Phylogenetic analysis of different N proteins of morbilliviruses revealed five well-defined clusters as observed previously. To the best of our knowledge this is the first report describing the nucleocapsid gene sequence of PPRV Indian isolate.

A total of 18 foot-and-mouth disease virus (FMDV) serotype Asia1 field isolates belonging to two different lineages (including the divergent group) as delineated earlier in VP1-based phylogeny were sequenced in the non-structural 3A and 3C protein-coding regions. The phylogenetic trees representing the regions coding for the non-structural proteins were very similar to that of the structural VP1 protein-coding region. Phylogenetic comparison at 3C region revealed clustering of Asia1 viruses with the isolates of serotypes O, A and C in the previously identified clade. Comparison of amino acid sequences identified lineage-specific signature residues in both the non-structural proteins. Overall analysis of the amino acid substitutions revealed that the 3A coding region was more prone to amino acid alterations than 3C region.

A single-tube one-step multiplex RT-PCR was standardized to amplify both 337 bp and 191 bp fragments of N and M genes of peste des petits ruminants virus (PPRV), respectively, and only a 337 bp fragment of N gene of Rinderpest virus (RPV). The RT-PCR using purified viral RNA was easily adopted for direct detection of PPRV in clinical field samples and its differentiation from RPV. The amplified N and M gene products were confirmed to be PPRV- and RPV-specific by their size in 1.5% agarose gel and restriction analysis. In the assay, the Qiagen one-step RT-PCR kit containing the Ominiscript and Sensiscript reverse transcriptases and Hot star Taq DNA polymerase was utilized. The sensitivity of the assay was found to be 100 fg of PPRV RNA. Compared with a two-step assay, the one-step assay is easier and time-saving as it requires just a single buffer for both reactions, reverse transcription (RT) and PCR. In experimentally infected goats, PPRV was detectable by the one-step RT-PCR in nasal and ocular swabs 7-17 days post infection (p.i.). and in oral swabs 7-15 days p.i. Out of 32 clinical field samples tested, 18 were positive by sandwich ELISA (S-ELISA), while 22 were positive by the one-step RT-PCR.

Metastasis to the thyroid gland is rare despite its rich vascular supply. Among the pulmonary malignancies metastasising to the thyroid, adenocarcinomas are the commonest. The appearance of metastatic disease in lung carcinoma indicates a poor prognosis and the average survival is two months. We report a 62-year-old woman with squamous cell carcinoma of lung metastatic to the thyroid that produced massive enlargement of the gland. The appearance of the secondary preceded the diagnosis of the primary malignancy by a few months. Ultimately, the patient succumbed to her disease.

Comparison of nucleotide sequences at the VP1 coding region of foot-and-mouth disease serotype Asia1 viruses from India has revealed two genetic lineages with emergence of a genetically divergent group in recent years. In this study a simple, fast, relatively costeffective multi-primer RT-PCR assay to differentiate genetic lineages of type Asia1 viruses was developed. Efforts were made in the design of novel lineage-specific primers and in optimization of the multi-primer assay protocol in conjunction with the use of the serotype specific primer for confirmation of serotype Asia1 virus. This assay promises to be an effective tool in molecular epidemiological investigation of FMD in the country.

The M gene nucleotide sequence of an Indian peste-des-petits ruminants (PPRV) vaccine virus ("PPRV Sungri/96") belonging to Asian lineage was determined. The gene is 1476 nucleotides long with a single open reading frame (ORF). The nucleotide and predicted amino acid sequence was compared with the homologous region of the African Lineage Vaccine virus "PPRV/Nigeria/75/1". The nucleotide sequence of the "PPRV Sungri/96" was 86% identical to that of "PPRV/Nigeria/75/1", while a homology of 93% and 95% could be observed in the ORF and amino acids level, respectively. The M gene encodes a protein of 335 amino acids, with a predicted molecular weight (MW) of 37.8 kDa. The ORF is flanked by a 3' untranslated region of 436 nucleotides and a high level of sequence divergence (approximately 30%) could be observed in this region between the vaccine viruses of Asian and African lineages. A high degree of conservation of several amino acids of this protein observed previously was also confirmed in this study.

Melnick-Needles syndrome or osteodysplasty, a monogenic heritable bone dysplasia, is characterized by a typical facies and characteristic radiological findings. Less than 70 well-documented cases have been reported in literature; most of them were sporadic. We report the first case from Eastern India in an adolescent male, who had cranio-vertebral junction anomalies and presented with spastic quadriparesis at the age of 13 years.

The amino acid composition of the two surface proteins of peste-des-petits ruminants vaccine virus belonging to lineage four from India were deduced from the nucleotide sequence. The fusion (F) protein gene of PPRV Sungri/96 is 2405 nucleotides long and in relation to the length, it is 80 nucleotides longer than that of PPRV Nigeria/75/1 which are found to be present at the 5'UTR of this virus. The complete F gene alignment with other morbillivirus reveals a homology of 89% with PPRV/Nigeria/75/1 and 48-51% with other morbilliviruses. The F protein of PPRV Sungri/96 exhibited characteristics similarity to those of other morbillivirus F proteins. The overall amino acid similarity with its counterpart PPRV Nigeria/75/1 was 96%; with other morbilliviruses it is 65-74%. The PPRV Sungri/96 haemagglutinin (H) protein gene is 1954 nucleotides long and showed a sequence homology of 90.7% with PPRV/Nigeria/75/1 and with other morbilliviruses it ranged from 33% to 45%. At amino acids level, PPRV Sungri/96 showed a homology of 92.3% with PPRV/Nigeria/75/1 and 34-49% with other morbilliviruses. The phylogenetic tree constructed for F and H gene reveals four separate groups which is very similar to that found in other genes. To the best of our knowledge this is the first report describing the F and H genes of an Indian isolate.

Nucleocapsid (N), matrix (M) and hemagglutinin (H) genes-based simplex PCRs and an N and M genes-based multiplex PCR were developed for detection of Peste-des-petits-ruminants virus (PPRV). The M gene PCR was the most sensitive, followed by N, H and an already described fusion (F) gene PCRs, as they could detect the virus in samples with titers of 101, 102, 104and 105 TCID50/ml, respectively. The multiplex PCR was as sensitive as the M gene PCR, but it had the advantage of differentiating PPRV from Rinderpest virus (RPV).

The complete nucleotide sequence of the large polymerase (L) protein of the peste-des-petits ruminants (PPR) vaccine virus (PPRV Sungri/96) belonging to the Asian lineage was determined. The gene was 6643 nucleotides in length from the gene-start to the gene-end and encoded a polypeptide of 2183 amino acids. The PPRV Sungri/96 has a nucleotide homology of 94.1% for PPRV Nigeria 75/1 to 64.4% for Canine distemper virus. At amino acid level PPRV Sungri/96 has an amino acid identity of 96.2% with PPRV Nigeria 75/1 and 70.4% to 74.8% with other morbilliviruses. All the established domains in L protein characteristic of paramyxoviruses were also found to be present in PPRV Sungri/96. Phylogenetic analysis of different L proteins of morbilliviruses revealed five well-defined clusters as observed previously. The 3' trailer sequence of PPRV Sungri/96 is of 37 nucleotides long which is very similar to that of other morbilliviruses. To the best of our knowledge this is the first report describing the polymerase gene sequence of PPRV Indian isolate.

Foot-and-mouth disease (FMD), the most economically important disease of cloven-hoofed animals, is endemic in India. Sequence analysis revealed that phylogenetic grouping of type Asia1 field isolates on the basis of the large fragment of the 5'untranslated region (5'LF-UTR) was quite similar to that based on the sequences of the capsid-coding (VP1) region of the same viruses. The existence of two distinct lineages of type Asia1 suggested by the study on the VP1 region was further supported by the detection of a difference in length and predicted secondary structure of the 5'LF-UTR between the two lineages. Sequence variability between the isolates of the two lineages was also observed within the different domains of the internal ribosome entry site (IRES) around conserved motifs like the GNRA,- RAAA,- and the polypyrimidine tract. Certain group and lineage-specific signature nucleotides pertaining to FMDV type Asia1 in the 5'LF-UTR have been identified. The present study shows that the 5'LF-UTR of FMDV serotype Asia1 field isolates are variable in relation to the length and probable secondary structure of the IRES.

Hepatocyte mitochondrion functions as a cause and as a target of liver injury. Since the mitochondria are under dual control of nuclear DNA and mitochondrial DNA (mtDNA), mutations in genes of both classes have been associated with inherited mitochondrial hepatopathies. Point mutations, deletions, insertions, rearrangements, DNA depletion--all have been identified. Many factors influence the prevalence of mitochondrial disorders, including the mutations rate, inheritance pattern, population structure, and the genetic background. In primary disorders, mitochondrial defect is the primary cause of liver disease often producing fatal hepatic failure in infancy or childhood. In secondary disorders, insult to mitochondria is caused by either a gene defect that affects non-mitochondrial proteins or by an exogenous injury to mitochondria. Diagnosis should be suspected in cases of liver disease with neuromuscular symptoms, multisystem involvement that cannot be explained by a single pathology or rapidly progressive liver failure in early childhood. Laboratory findings in the blood and urine show an altered redox status. Various antioxidants, vitamins, cofactors, and electron acceptors have been for proposed but none is effective. Presence of neuromuscular or extraintestinal involvement in primary disorder precludes the use of liver transplantation.

Chorea, hemichorea, hemiballismus and other parkinsonian movement disorders have been described in type 1 diabetic patient with uncontrolled hyperglycemia. In comparison, abnormal movements in diabetic ketoacidosis are rare though ketosis due to other causes can cause parkinsonism-like movement disorders. We report two cases of diabetic ketoacidosis where hemifacial spasm was the predominant clinical manifestation for which no organic cause could be detected with relevant investigations. The symptoms subsided with conventional therapy for diabetic ketoacidosis and never recurred.

Effect of virulent and attenuated peste des petits ruminants (PPR) virus on the immune response to nonspecific antigen (ovalbumin) was investigated. Clinical and serological responses were monitored in goats administered with ovalbumin concurrently with either PPR vaccine or virulent virus. Study showed that PPR virulent virus causes marked immunosuppression as evidenced by leukopenia, lymphopenia, and reduced early antibody response to both specific and nonspecific antigen. These observations were predominant particularly during acute phase of disease (4-10 days post-infection). On the other hand, the vaccine virus induced only a transient lymphopenia without significantly affecting the immune response to nonspecific antigen or to itself during this period. Further, the antibody levels to ovalbumin in the group administered with virulent PPRV increased significantly between days 28 and 35 post-infection in comparison to the titers in other two groups given with either ovalbumin alone or in combination with vaccine.

The capsid-coding (P1) and 3A regions of foot-and-mouth disease virus (FMDV) type A field isolates including two vaccine strains collected during 1977-2000 were analyzed. In the phylogenies, the isolates were distributed into two previously identified genotypes VI and VII, with multiple sub-genotypes that are temporally clustered. Comparison of the antigenic relationships of field isolates with the two vaccine strains (IND 17/77 and IND 490/97) and the reference strains of the genotypes VI (IND 233/99) and VII (IND 40/00) indicated two broad antigenic groups that correlate with the phylogenetic groupings (genotypes VI and VII), and are highly divergent from the vaccine strains. The maximum likelihood method of selection analysis identified a number of amino acid sites within the P1 region to be under weak positive selection. Some of the positively selected sites were mapped at/near the antigenically critical amino acid sites of the P1 region, indicating host immune pressure as one of the important driving force behind the observed genetic and antigenic diversity in FMDV. A small number of selected sites are located in the heparan sulphate-binding pocket of the virus, suggesting a fitness advantage for cell entry of the virus. No positive selection was detected in the 3A dataset.