KIR diversity in three ethnic populations of Assam state, Northeast India.

Killer immunoglobulin-like receptors (KIR) exhibit extensive diversity and it has been observed that populations with different ethno-history, linguistic, geographic and genetic backgrounds can differ in KIR profile. In this context, we have investigated the KIR complex in three ethnic populations-Kachari (n = 108), Ahom (n = 104) and Adivasi (n = 101) of Assam, Northeast India. The three populations had 145 distinct KIR genotypes in 313 individuals typed. The two Mongoloid populations--Kachari and Ahom had close genetic affinities with their parental East Asian groups where the Kachari clustered with Chinese populations and the Ahom in another clade clustered with Thailand Bangkok and Polynesian populations. The Adivasi differed markedly from these Mongoloid populations in having higher KIR 2DL2, 2DS2, 2DS3 and 2DS5, but lower 2DL3 (P value <0.0001). Like the other native Indian populations, the Adivasi had higher share of Bx-haplogroup and C4Tx genotype (37/101). However, unlike other Indian populations, KIR 3DS1 gene frequency was lower in Adivasi (21%) and was comparable to the African populations. The neighbor-joining dendogram generated on the basis of KIR gene frequencies of our study populations with 43 world populations also placed the Adivasi with African populations. Interestingly, the three populations in the dendogram are consistent with their migration histories. In summary, our data suggest that KIR profile of the three ethnic populations displayed ethnic diversity and was consistent with their migration history thereby supporting the concept that KIR diversity may be used to understand genetic affinity and migration history of populations.

Contribution of medical colleges to tuberculosis control in India under the Revised National Tuberculosis Control Programme (RNTCP): lessons learnt & challenges ahead.

Medical college faculty, who are academicians are seldom directly involved in the implementation of national public health programmes. More than a decade ago for the first time in the global history of tuberculosis (TB) control, medical colleges of India were involved in the Revised National TB Control Programme (RNTCP) of Government of India (GOI). This report documents the unique and extraordinary course of events that led to the involvement of medical colleges in the RNTCP of GOI. It also reports the contributions made by the medical colleges to TB control in India. For more than a decade, medical colleges have been providing diagnostic services (Designated Microscopy Centres), treatment [Directly Observed Treatment (DOT) Centres] referral for treatment, recording and reporting data, carrying out advocacy for RNTCP and conducting operational research relevant to RNTCP. Medical colleges are contributing to diagnosis and treatment of human immunodeficiency virus (HIV)-TB co-infection and development of laboratory infrastructure for early diagnosis of multidrug-resistant and/or extensively drug-resistant TB (M/XDR-TB) and DOTS-Plus sites for treatment of MDR-TB cases. Overall, at a national level, medical colleges have contributed to 25 per cent of TB suspects referred for diagnosis; 23 per cent of 'new smear-positives' diagnosed; 7 per cent of DOT provision within medical college; and 86 per cent treatment success rate among new smear-positive patients. As the Programme widens its scope, future challenges include sustenance of this contribution and facilitating universal access to quality TB care; greater involvement in operational research relevant to the Programme needs; and better co-ordination mechanisms between district, state, zonal and national level to encourage their involvement.

An innovative surgical technique for treating penile incarceration injury caused by heavy metallic ring.

Penile incarceration injury by heavy metallic ring is a rare genital injury. A man may place metal object for erotic or autoerotic purposes, for masturbation or increasing erection, and due to psychiatric disturbances are some of the reasons for a penile incarceration injury. The incarcerating injury results in reduced blood flow distal to the injury, leading to edema, ischemia, and sometimes gangrene. These injuries are divided into five grades and their treatment options are divided into four groups. Surgical techniques are reserved for the advanced grades (Grades IV and V). We describe an innovative surgical technique, which can be adopted in Grades II and III injuries.

Identification of a novel cluster of PCV2 isolates from Meghalaya, India indicates possible recombination along with changes in capsid protein.

Documentation of the emergence of Porcine circovirus 2 (PCV2) infection and economic losses incurred due to high mortality has been reported worldwide. The prevalence and genetic diversity of the virus has been reported in Northeast India including the possible chances of Classical swine fever virus (CSFV) vaccine failure in pig population in this region resulting in major disease outbreak. Irrespective of the genetic variability, the emergence of a novel cluster (based on the ORF2 phylogeny) was reported last year. The present study describes a state-wide (Meghalaya, India) molecular epidemiological investigation of PCV2 strains in pig population by amplification, sequencing and undertaking phylogenetic analyses. The results indicate the identification of a novel cluster of PCV2 originating from the inter-genotypic recombination between PCV2c and PCV2d. Multiple sequence alignment of amino acids indicates possible substitution in the A, B and C domains of the capsid protein. Molecular structural modelling of the capsid protein of PCV2 indicated possible motif variations in the secondary structure including presence of a tunnel, encountered at the interface region on each chain facilitating in transportation of molecules and acting as an active site for attachment and penetration. The baseline data strengthens the existing control programme of PCV2 and is possibly helpful in the planning of active surveillance strategy in this region.

A randomized trial comparing the efficacy of four treatment regimens for uncomplicated falciparum malaria in Assam state, India.

A four-arm drug sensitivity study compared chloroquine, sulfadoxine-pyrimethamine (SP), mefloquine and mefloquine-artesunate in Sonitpur and Karbi Anglong districts in Assam state, India. Two criteria were used to ascertain outcome: success of clinical treatment and parasitologic cure. In Sonitpur, at 14 days, there were 36/56 early and late treatment failures plus late parasitologic failures to chloroquine and 16/56 for SP. In Karbi Anglong, combined treatment failure at 14 days was 16/56 to chloroquine and 8/60 to SP. Mefloquine and mefloquine-artesunate demonstrated 93.9% and 93.6% sustained responses respectively at 42 days. High failure rates to both chloroquine and SP preclude the use of these drugs as first-line treatment for uncomplicated falciparum malaria in this region. A mefloquine-artesunate combination presents an effective alternative utilizing the currently recommended higher dose of mefloquine.

Neuroleptic effects on serine and glycine metabolism.

The concentrations of serine and glycine and the activity of serine hydroxymethyltransferase (SHMT) are abnormal in plasma and brains of schizophrenics. To further elucidate the possible role of neuroleptics on the metabolism of serine and glycine and the activity of SHMT, we studied the plasma of controls and schizophrenics on and off medications, the brains of rats treated with haloperidol, and the activity of purified SHMT in the presence or absence of haloperidol and fluphenazine. Plasmas of neuroleptic-treated schizophrenics had nonsignificantly lower concentrations of serine and glycine. Brains of haloperidol-treated rats had significantly lower concentrations of serine and glycine. At therapeutic levels haloperidol and fluphenazine did not inhibit the activity of purified SHMT. The serine-glycine lowering effects of haloperidol and neuroleptics are discussed in the context of a possible neuroprotective potential of neuroleptics in schizophrenia.

Deficient NMDA-mediated glutamate release from synaptosomes of schizophrenics.

Previous studies from our laboratory indicated that the veratridine-induced release of glutamate and GABA from synaptosomes derived from brains of schizophrenics was decreased. In the present study, synaptosomes were prepared from frozen brain samples from schizophrenics and from controls. Stimulation by 10 mumol/L 2-amino-3-hydroxy-5-methoxylisoxazole-4-propionic acid (AMPA) produced equal glutamate release from both groups. Release induced by either 10 mumol/L kainic acid (KA) or n-methyl-d-asparate (NMDA) was reduced significantly in the preparations derived from schizophrenics. Similarly, the amount of GABA released by 50 mumol/L glutamate was also reduced in the schizophrenic-derived synaptosomes. However, in membranes derived from the crude synaptosomal pellet, no differences between the controls and schizophrenics were observed in measures of total glutamate binding or its displacement by NMDA. The data demonstrate a deficiency in NMDA (and possibly KA) receptor functioning schizophrenics and support the "second-generation" theories of schizophrenia as a glutamatergic deficiency disorder.

Tardive dyskinesia exacerbated after ingestion of phenylalanine by schizophrenic patients.

Despite continued research, the influences that promote or exacerbate tardive dyskinesia (TD) symptoms remain incompletely understood. Recent findings (Gardos et al. 1992; Richardson et al. 1989) suggest that ingestion of the dietary constituent, phenylalanine, might exacerbate TD symptoms, but a double-blind, placebo-controlled challenge had not previously been conducted in schizophrenic patients. On two different mornings, in counterbalanced order, 18 male schizophrenic patients with TD were challenged with either 100 mg/kg phenylalanine or placebo. Effects on abnormal involuntary movements, recall memory, and plasma phenylalanine were measured 90 minutes post-challenge. The results supported the hypothesis in that involuntary movements increased to a statistically and clinically meaningful degree after the phenylalanine challenge, but not after placebo. No effects on memory were detected. Significant order effects characterized the plasma findings but not the behavioral data. Results indicate that a dietary constituent, the amino acid phenylalanine, can potentially exacerbate tardive dyskinesia symptoms in schizophrenic patients. The influence of phenylalanine and other ingested substances on clinical symptomatology warrants further investigation.

A hyperglycinergic rat model for the pathogenesis of schizophrenia: preliminary findings.

There is evidence of high glycine concentrations in the brains and periphery of schizophrenics. In the forebrain, glycine plays a major role as a co-agonist with glutamate at the excitatory N-methyl-D-aspartate (NMDA) receptors. This activity of glycine is involved in the normal functioning of the brain in adulthood and during neurodevelopment, and it may also cause neurotoxicity and brain abnormalities when its concentrations are high. To test the hypothesis that the high glycine concentrations observed in schizophrenics play an etiologic role in schizophrenia, an animal model was tested where rats were made hyperglycinic from life in utero to adulthood. The hyperglycinic rats showed abnormalities in sensory gating mechanisms, enlarged cerebral ventricles and diminished hippocampal dimensions. All of these abnormalities closely parallel observations reported in patients with schizophrenic psychoses. These results from a rat model suggest an etiologic role for high glycine concentration in the behavior and brain abnormalities of schizophrenic patients.

Abnormal serine-glycine metabolism in the brains of schizophrenics.

The metabolism of serine and glycine as studied in the plasma is abnormal in schizophrenics and psychotics. There is a concomitant abnormality of the enzyme serine hydroxymethyl transferase (SHMT). To study the status of serine-glycine metabolism in brains of schizophrenics and controls, frozen autopsied brain tissues were obtained from medial and lateral temporal lobes. The results show that the apparent Km of SHMT and the concentrations of serine and glycine are significantly higher only in the medial temporal lobe areas of schizophrenics when compared to controls. These findings are discussed in the context of the role of glycine and serine as enhancers of glutamatergic excitotoxicity and consequent development of morphological abnormalities in the brains of schizophrenics.

Long-term consequences of prenatal cocaine exposure on biogenic amines in the brains of mice: the role of sex.

Prenatal cocaine exposure leads to multiple abnormalities in the mature offspring. We explored the effects of gestational exposure to cocaine on neurotransmitter systems of adult mice. The subjects were the mature offspring of mice (a) prenatally fed cocaine between gestational day (G) 8 and G19, (b) pair-fed chow and water, or fed chow and water ad libitum. The forebrains of the mature offspring were assayed for monoamines and amino acids. Cocaine exposure particularly affected the dopaminergic system and in a sex-specific manner. In males dopamine concentrations were decreased and dopamine turnover was increased, whereas in females dopamine concentrations were increased and turnover was decreased. Neither norepinephrine, the serotonergic system, nor neuroactive amino acids (or their precursors) were affected by cocaine. Thus, in utero exposure to cocaine produces long-lasting, specific defects in the dopaminergic system.

Abnormal serine hydroxymethyl transferase activity in the temporal lobes of schizophrenics.

We studied the kinetics of the enzyme serine hydroxymethyl transferase (SHMT) and the concentration of its metabolic substrates serine and glycine, in the postmortem brains of controls and schizophrenics. The Km of SHMT, and the concentration of serine and glycine were all significantly higher in the temporal lobes of brain tissues from schizophrenics than in those from controls. These differences were not observed in the frontal lobe specimens. Neuroleptics, age, sex and autolysis time did not contribute to these differences. The role of SHMT deficiency in schizophrenia is discussed in relation to the production of glycine and 1-carbon units from which purines and thereby adenosine is produced. Both glycine and adenosine are potent neuromodulatory substances for the release of dopamine and glutamate, neurotransmitters which have been implicated in the pathophysiology of schizophrenia.

Evidence of glutamatergic deficiency in schizophrenia.

Studies of amino acid release were carried out using frozen sections from brains of schizophrenics and controls. Synaptosomes were prepared via differential centrifugation in Ficoll allowing the veratridine-induced release of aspartate, glutamate, glycine, and GABA to be measured. The release of glutamate and gamma-aminobutyric acid (GABA) was reduced in the synaptosomes from schizophrenics. This decrease could be reversed partially by pre-incubation of the synaptosomes with haloperidol. Additionally, the activity of glutamate decarboxylase was decreased and partially restored by haloperidol pre-incubation. These data are consistent with the hypothesis of a glutamatergic/GABAergic deficit in schizophrenia.

Plasma serine in schizophrenics and controls measured by gas chromatography-mass spectrometry.

In several previous studies, we reported significantly higher plasma serine concentrations in psychotic (and schizophrenic) subjects compared with nonpsychotic and control subjects. In those studies, we used a gas chromatography technique to assay the amino acids. Perry and Hanson (1985), using cation-exchange chromatography to assay plasma amino acids, found no differences in the plasma serine concentrations of controls compared with schizophrenic patients. They criticized our work on technical grounds and suggested that some other substance was co-eluting with the gas chromatographic serine peaks in our assays. We have now examined the plasma of schizophrenic and control subjects with gas chromatography-mass spectrometry (GC-MS), where accurate amino acid quantitation relative to a known internal standard can be achieved. The results show that the plasma serine concentrations of schizophrenic patients are significantly higher than those of controls. Also, plasma glycine concentrations are significantly higher in schizophrenic patients compared with controls.

Psychosis and vulnerability to ECT-induced seizures.

Medical records of patients with major depressive disorders who had received electroconvulsive therapy (ECT) for the first time were studied to test the hypothesis that psychotic patients are more vulnerable to seizures than nonpsychotic patients. This hypothesis was based on studies suggesting a putative purinergic deficiency in psychosis. Results showed that the duration of ECT-induced seizures as a measure of seizure vulnerability was significantly longer in psychotic than in nonpsychotic depressive patients. The association applied for the first ECT as well as for the course of eight ECTs. These findings were still present when covariates such as age, electrical energy applied, dosage of methohexital and succinylcholine, and psychotropic medications such as neuroleptics, benzodiazepines, and tricyclics were included in the statistical analysis. The results are discussed in the context of the role of neurotransmitters such as glutamate, gamma-aminobutyric acid, adenosine, and dopamine on seizure vulnerability and psychosis.

Growth-associated production of poly-3-hydroxybutyrate by Bacillus mycoides.

Bacillus mycoides strain RIJ B-017, a growth-associated poly-3-hydroxybutyrate (PHB) producer was grown on sucrose-containing media. PHB accumulated in cells up to 72% of dry cell mass. The overall maximum value of PHB yield (Yp/s) and productivities (Qp and qp) 250 mgp/gs, 120 mgp L-1 h-1 and 30 mgp gx-1 h-1, respectively, were obtained at 15 g/L sucrose. Differential scanning calorimeter heating curve showed two peaks, one at 95.9 degrees C and another at 165.4 degrees C with a shoulder around 154.6 degrees C. The viscosity-average molar mass in chloroform at 27 degrees C was 505 kDa. The carbon content of PHB was 55.4% of the mass.

Seasonal prevalence of Aedes aegypti in urban and industrial areas of Dibrugarh district, Assam.

In Dibrugarh district, one of the most populous districts of Assam, there is a potential risk of dengue virus transmission by the mosquito Aedes aegypti during the autumn, in the urban and industrial areas of the district. The seasonal patterns of oviposition activity and abundance of breeding sites of this vector were studied in two areas of the district. From January 2010 to December 2010, we examined a total of 767 ovitraps and 6562 water filled containers. Both study areas showed high percentages of positive ovitraps (urban: 18.2% and industrial: 45.08%) and positive breeding sites (urban: 22.8% and industrial: 53.5%) for Aedes aegypti with higher abundance in the post monsoon season. In industrial areas, percentages of breeding sites and positive ovitraps were high as compared to the percentages in the urban areas. The percentages of breeding sites and the positive ovitraps are high in autumn when compared to the percentages of the other seasons. In both the areas and with both the methodologies the highest infestation levels were registered in October (ovitraps: 29.3% and 65.1%, breeding sites: 27.5% and 65.2%). This highest abundance took place after heavy rainfall. A sharp decline in oviposition activity was observed when monthly room temperature decreased to16ºC with low rainfall (38 mm).

Role of primary chemotherapy in management of large tumors of undescended testis: Our experience.

OBJECTIVE: This study aimed to share our experience with tumors of undescended testis (UDT) and to assess the impact of primary cisplatin-based chemotherapy on such tumors. MATERIALS AND METHODS: This study included the cases of tumor in UDT from February 2005 to December 2011. Evaluation of the cases was done with proper clinical examination and laboratory investigations along with tumor markers (alfa-feto protein, beta-human chorionic gonadotropin, lactate dehydrogenase) and contrast-enhanced computed tomography abdomen. Fine needle aspiration cytologywas done in all cases. Primary chemotherapy with three cycles of bleomycin, etoposide, and cisplatin regimen at three weekly intervals started in all cases. Response to treatment was seen after four weeks of the third cycle. RESULTS: Fourteen cases (12.5%) of germ cell tumor in UDT out of 112 cases of germ cell tumor of the testis were included. The age ranged from 16-60 years. Histological diagnosis was pure seminoma in all cases. After three cycles of BEP regime, complete response was seen in 11 cases and partial response in three cases where the residual tumor was excised along with retroperitoneal lymph node dissection RPLND. Of the 14 cases, 13 were in regular follow-up and one was lost to follow-up. All on follow-up were doing well without recurrence till now. CONCLUSION: Surgical removal of the primary tumor in UDT with or without bulky metastasis is complicated. Primary chemotherapy with cisplatin-based regimen is a good option in such cases.