Culprit vessel only versus complete revascularization following thrombolysis in patients with ST elevation myocardial infraction and multivessel coronary artery disease - A prospective study.

OBJECTIVE: The present study compares the treatment outcomes of only culprit vessel PCI and complete revascularization in patients with STEMI and multivessel disease (MVD) following thrombolysis. METHODS: This was a single-center, prospective randomized study including a total of 108 patients presenting at a tertiary care center within 3-24 h post-thrombolysis and undergoing pharmacoinvasive PCI, and randomized into two groups: complete revascularization PCI group and culprit only PCI group. The primary outcomes were evaluated by cardiac mortality, repeat myocardial infarction (MI)/acute coronary syndrome (ACS) and refractory angina. The secondary outcomes include repeat revascularization and safety outcomes namely contrast induced nephropathy (CIN), cerebrovascular accident (CVA) and major bleeding were compared among both the groups at one year follow-up. RESULTS: Complete revascularization PCI group and culprit only PCI group had 54 patients in each group. Left ventricular ejection fraction did not show significant difference at discharge (p = 1) but was significantly improved in complete revascularization PCI group (p = 0.001) at one year follow-up. Reduced number of outcomes with a significant difference in both the groups were seen for primary outcomes such as cardiac mortality (p = 0.01), repeat MI/ACS (p = 0.01) and refractory angina (p = 0.038) along with repeat revascularization (p = 0.001) at one year follow-up. Complete revascularization did not show any statistically significant difference for CIN (p = 0.567), CVA (p = 0.153) and major bleeding (p = 0.322) then culprit only revascularization group. CONCLUSION: In patients with STEMI and MVD, complete revascularization was found more favourable in terms of primary and secondary outcomes compared to culprit only revascularization.

Elucidation of dominant energy metabolic pathways of methane, sulphur and nitrogen in respect to mangrove-degradation for climate change mitigation.

Mangroves play a key role in ecosystem balancing and climate change mitigation. It acts as a source and sink of methane (CH4), a major greenhouse gas responsible for climate change. Energy metabolic pathways of methane production (methanogenesis) and oxidation (methanotrophy) are directly driven by sulphur (S) and nitrogen (N) metabolism and salinity in coastal wetlands. To investigate, how mangrove-degradations, affect the source-sink behaviour of CH4; the pathways of CH4, S and N were studied through whole-genome metagenomic approach. Soil samples were collected from degraded and undisturbed mangrove systems in Sundarban, India. Structural and functional microbial diversities (KEGG pathways) of CH4, S and N metabolism were analysed and correlated with labile carbon pools and physico-chemical properties of soil. Overall, the acetoclastic pathway of methanogenesis was dominant. However, the relative proportion of conversion of CO2 to CH4 was more in degraded mangroves. Methane oxidation was higher in undisturbed mangroves and the serine pathway was dominant. After serine, the ribulose monophosphate pathway of CH4 oxidation was dominant in degraded mangrove, while the xylulose monophosphate pathway was dominant in undisturbed site as it is more tolerant to salinity and higher pH. The assimilatory pathway (AMP) of S-metabolism was dominant in both systems. But in AMP pathway, adenosine triphosphate sulfurylase enzyme reads were higher in degraded mangrove, while NADPH-sulfite reductase abundance was higher in undisturbed mangrove due to higher salinity, and pH. In N-metabolism, the denitrification pathway was predominant in degraded sites, whereas the dissimilatory nitrate reduction pathway was dominant in undisturbed mangroves. The relative ratios of sulphur reducing bacteria (SRB): methanogens were higher in degraded mangrove; however, methanotrophs:methanogens was higher in undisturbed mangrove indicated lower source and greater sink capacity of CH4 in the system. Microbial manipulation in mangrove-rhizosphere for regulating major energy metabolic pathways of methane could open-up a new window of climate change mitigation in coastal wetlands.

Pulsatile flow in descending aorta: Can coarctation of aorta be ruled out by transesophageal echocardiography?

A 5-year-old child with L posed great arteries, large subpulmonic ventricular septal defect (VSD), atrial septal defect (ASD), and a large patent ductus arteriosus (PDA) with mild isthmic narrowing was scheduled for surgical correction. Intraoperatively, it was a case of anatomically corrected malposition of great arteries. Due to abnormal positioning of great vessels, the isthmus was ligated instead of the large PDA. The postoperative transesophageal echocardiography showed pulsatile flow in descending aorta as it was being filled by large PDA, and thus iatrogenic coarctation (CoA) was missed. It was detected in the intensive care unit due to the onset of acidosis on blood gas analysis and the presence of gradient between radial and femoral arterial line pressures. The patient was taken for redo surgery, the PDA was then ligated, resection of the isthmic narrowing and repair by end-to-end anastomosis was done.

Work zone noise levels at Aarti steel plant, Orissa and its attenuation in far field.

The outdoor noise levels from the various work places of the integrated steel plant were measured. The average noise level (L(eqst)) at the outdoor was found between 59-84 dBA. The combined noise level (L(eq)) of the plant was 90 dBA and 92 dBA on 1.12.2006 and 1612.2006, respectively. The noise levels in the far fields were found between 43-70 dBA for daytime and meet the noise quality for industrial (75 dBA) area and residential (55 dBA) areas. Maximum attenuation of 47-49 dBA of noise level was found at worker's colony and may be attributed mainly to the ground absorption. As the air quality standards of the area in respect of noise in the ambient is tending to increase, engineering control measures suggested to the noisiest equipments for better economically viable and higher payback period.

Budd-Chiari syndrome, ascites and shunt malfunction due to hyperosmolar hypernatremia in operated pediatric craniopharyngiomas: a red herring.

INTRODUCTION: Postoperative management of sellar and suprasellar lesions in children involves regular evaluation of fluid, electrolyte, and neuroendocrine parameters. On discharge, maintenance of water homeostasis is difficult especially among those with access to only basic primary health care. Complications of a chronic hypernatremic state can lead to severe morbidity and mortality. CASES: The authors present two cases of craniopharyngioma who developed inferior vena cava thrombosis, Budd-Chiari syndrome, and shunt malfunction postoperatively. Factors which predispose to a hypercoagulable state are evaluated along with measures undertaken to identify and treat the cause of ascites and shunt malfunction. DISCUSSION: The role of hypernatremia, serum hyperosmolality, and Vasopressin analogs in the pathology are discussed along with imaging and treatment.

Development and evaluation of SYBR Green I-based one-step real-time RT-PCR assay for detection and quantification of Chikungunya virus.

The development of a one-step SYBR Green I-based real-time RT-PCR assay is reported for detection and quantification of Chikungunya virus (CHIKV) in acute-phase patient serum samples by targeting the E1 structural gene. A linear relationship was obtained between the virus concentration and cycle threshold (C(t)) value over a range of 10(7)-0.1PFU/ml. The reported assay was found to be 10-fold more sensitive compared to conventional RT-PCR with a detection limit of 0.1PFU/ml. The feasibility of this reported assay system for clinical diagnosis was validated with 51 suspected acute-phase serum samples of the recent CHIKV epidemic in southern India, 2006. The comparative evaluation with acute-phase patient serum samples revealed the higher sensitivity of real-time RT-PCR assay by picking up six additional samples with low copy number of template. None of the healthy serum samples analyzed in this study showed amplification. The quantification of the viral load in the acute-phase serum samples was also determined employing the standard curve, which varies from 0.1 to 10(7)PFU/ml. These findings demonstrated that the reported assay has the potential usefulness for clinical diagnosis due to simultaneous detection and quantification of Chikungunya virus in acute-phase patient serum samples.

Fusogenic peptide as diagnostic marker for detection of flaviviruses.

BACKGROUND: Dengue, Japanese encephalitis, West Nile encephalitis, yellow fever are the common flaviviral diseases associated with high morbidity and mortality. The initial symptoms of most of the flaviviral infections are similar to each other as well as to some other viral diseases. Making clinical diagnosis, therefore, becomes a challenging task for the clinician. Several studies have been reported on using detection of serum antibodies against flavivirus for the diagnosis of specific flaviviral disease; no field-based pan-flavi virus detection system is available, which can be used in low-endemicity areas for differentiation of flaviviral disease from other viral diseases. AIM: To identify a conserved amino acid sequence among all flaviviruses and evaluate the antibody formed against the conserved peptide to develop pan-flavivirus detection system. MATERIALS AND METHODS: In the present study we have compared amino acid sequences of several flaviviruses and identified a conserved amino acid sequence lying in domain II of envelope protein. RESULTS: A peptide having the conserved amino acid sequence was used to generate polyclonal antibodies and these antibodies were used to detect several flaviviruses. Anti-peptide polyclonal antibodies selectively recognized flaviviruses and did not detect non-flaviviruses. Anti-peptide antibodies detected presence of virus in serum spiked with pure virus preparations. CONCLUSION: The study offers a rationale for development of pan-flavivirus capture assay suitable for low endemic areas.

Mechanism of ricin-induced apoptosis in human cervical cancer cells.

The mechanism of ricin-induced apoptosis in human cervical cancer cell line HeLa was studied. The present study demonstrated that ricin induces apoptosis of human cervical cancer cells (HeLa) in a time dependent manner with an IC(50) for cell viability of 1 microg/ml. Ricin treatment resulted in a time dependent increase in LDH leakage, DNA fragmentation, percent apoptotic cells, generation of reactive oxygen species and depletion of intracellular glutathione levels. DNA agarose gel electrophoresis showed typical oligonucleosomal length DNA fragmentation. Additionally, DNA diffusion assay was performed to confirm DNA damage and apoptosis. Ricin activated caspase-3 as evidenced by both proteolytic cleavage of procaspase-3 into 20 and 18 kDa subunits, and increased protease activity. Caspase activity was maximum at 4h and led to the cleavage of 116 kDa poly(ADP-ribose) polymerase (PARP), resulting in the 85 kDa cleavage product. Ricin-induced caspase-3 activation also resulted in cleavage of DNA fragmentation factor-45 (DFF45/ICAD) and DFF40 or caspase-activated DNase in HeLa cells. Activation of caspase-3, cleavage of PARP and DNA fragmentation was blocked by pre-treatment with caspase-3 specific inhibitor Ac-DEVD-CHO (100 microM) and broad-spectrum caspase inhibitor Z-VAD-FMK (40 microM). Ricin-induced DNA fragmentation was inhibited by pre-treatment with PARP inhibitors 3-aminobenzamide (100 microM) and DPQ (10 microM). Our results indicate that ricin-induced cell death was mediated by generation of reactive oxygen species and subsequent activation of caspase-3 cascade followed by down stream events leading to apoptotic mode of cell death.

Performance in long-term memory tasks is augmented by a phosphorylated growth factor receptor fragment.

To elucidate the role of enhanced phosphoinositide-3-kinase (PI3-kinase) activity in memory, a synthetic phosphopeptide (TAT-YPMDM) containing the p85 regulatory subunit receptor-binding motif (YXXM) coupled to the cell transduction domain of HIV-TAT protein was employed. This phosphopeptide bound the p85 subunit of PI3-kinase, and was internalized by both granule and pyramidal neurons when injected into the hippocampus. Increased lipid kinase activity and enhanced phosphorylation of the PI3-kinase substrates Akt (protein kinase B) and ribosomal S6 kinase were associated with TAT-YPMDM administration. Bilateral infusion of the phosphopeptide into the dorsal hippocampus after training improved performance in three hippocampus-dependent memory tasks: contextual fear conditioning, trace fear conditioning, and the Morris water maze. Both the biochemical and behavioral effects of the TAT-YPMDM phosphopeptide could be blocked by wortmannin. No effect was observed when a nonphosphorylated peptide (TAT-YMDM), or a second, unrelated phosphopeptide (TAT-YPLDL) was utilized. In addition, infusion of the TAT-YPMDM phosphopeptide did not interfere with memory acquisition or 4 hr memory. In addition, pretesting administration did not affect the ability to recall a previously established long-term memory. These findings suggest that stimulation of PI3-kinase activity by phosphorylated receptor fragments containing the YMDM motif augments long-term memory.

Myxoma of maxilla.

A case of Myxoma involving left Maxilla, presenting as swelling of left side of face and Oral cavity with bilateral nasal obstruction is reported.

Use of radiofrequency ablation in the modified maze procedure.

Atrial fibrillation secondary to long-standing mitral valve disease is very common. The maze procedure carried out along with mitral valve surgery reverts many of these patients back to sinus rhythm. Using radiofrequency ablation to carry out the maze procedure during mitral valve surgery gives results comparable to those from the Cox surgical maze procedure. We present our experience with 3 patients of rheumatic mitral valvular disease in whom radiofrequency ablation was used for the maze procedure.

Atrial fibrillation in patients with pure isolated severe rheumatic mitral regurgitation.

OBJECTIVE: This study examines the significance of the parameters that identify patients with mitral regurgitation (MR) and atrial fibrillation (AF) and discusses the indications for surgery in such patients. METHODS: Patients with MR and chronic AF (group I, n=64) and those without AF (group II, n=138) were studied by clinical and echocardiographic methods. Stepwise regression analysis identified factors associated with the presence of atrial fibrillation. RESULTS: Group I patients were older and more symptomatic. They had larger left ventricular (LV) end systolic dimension (4.6+/-1.1 cm vs 3.8+/-0.8 cm, p=0.03), left atrial (LA) dimension (5.4+/-2.0 cm vs 4.1+/-1.3 cm, p=0.02), LA area (55.9+/-27.1 cm2 vs 35.9+/-17.5 cm, p=0.003) and lower LV ejection fraction (58.8+/-8.0% vs 72.4+/-7.4%, p=0.0003). Right ventricular systolic pressure was higher (57.6+/-18.1 mm Hg vs 33.6+/-12.1 mm Hg, p=0.02). By stepwise regression analysis, factors that predicted the presence of AF were age (p < 0.03) and LA dimension (p < 0.01). A higher LV end systolic dimension and lower LV ejection fraction than the recommended value for good operative outcome were present in them. Emerging indications for surgery and predictors of poor outcome were seen. CONCLUSIONS: Atrial fibrillation in MR indicates a more chronic and severe disease process with worsening of left as well as right sided haemodynamics in spite of digoxin. Drifting towards decompensation, these patients are likely candidates for early surgery.

Teratoma masquerading as catamenial pleural effusion.

Pleural effusion is a common clinical entity in medical practice. We report a case wherein extensive investigations failed to yield a diagnosis and medical management including repeated thoracocentesis left the effusion refractory. The patient, a 26 years lady, gave a definite history of catamenial dry cough and wheeze. The mystery was unraveled following exploratory thoracotomy when a giant mediastinal teratomatous cyst with luteinized ovarian tissue was discovered and removed, leading to eventual cure for the patient.

Caspase activity plays an essential role in long-term memory.

Activation of intracellular second messenger cascades has been linked to learning and memory in various organisms. Identification of down-stream targets of these second messengers that play a role in learning and memory is an active area of research. Recently, it has been reported that increases in intracellular calcium can activate a cysteine-dependent aspartate-directed protease (caspase) cascade in mice. Using an antibody that selectively recognizes activated caspase-3, we detected the presence of this enzyme in hippocampal neurons. Inhibition of caspase activity in the hippocampus blocked long-term, but not short-term, spatial memory. These results suggest that a caspase-mediated cellular event(s) in hippocampal neurons is critical for long-term spatial memory storage.

Requirement for DARPP-32 in progesterone-facilitated sexual receptivity in female rats and mice.

DARPP-32, a dopamine- and adenosine 3',5'-monophosphate (cAMP)-regulated phosphoprotein (32 kilodaltons in size), is an obligate intermediate in progesterone (P)-facilitated sexual receptivity in female rats and mice. The facilitative effect of P on sexual receptivity in female rats was blocked by antisense oligonucleotides to DARPP-32. Homozygous mice carrying a null mutation for the DARPP-32 gene exhibited minimal levels of P-facilitated sexual receptivity when compared to their wild-type littermates. P significantly increased hypothalamic cAMP levels and cAMP-dependent protein kinase activity. These increases were not inhibited by a D1 subclass dopamine receptor antagonist. P also enhanced phosphorylation of DARPP-32 on threonine 34 in the hypothalamus of mice. DARPP-32 activation is thus an obligatory step in progestin receptor regulation of sexual receptivity in rats and mice.

Sphingosine-1-phosphate induces apoptosis of cultured hippocampal neurons that requires protein phosphatases and activator protein-1 complexes.

In this study, we report that mobilization of internal Ca2+ by sphingosine-1-phosphate, a metabolite of ceramide, induces apoptosis in cultured hippocampal neurons. This sphingosine-1-phosphate-induced apoptosis is dependent upon the activation of protein phosphatases, possibly calcineurin and phosphatase 2A (or a related phosphatase). In addition, pretreatment of neurons with double-stranded oligonucleotides containing the metallothionein phorbol-12-myristate-13-acetate response element sequence as transcription factor decoys suppressed apoptosis. In contrast, double-stranded oligonucleotides containing either the c-jun or SV40 phorbol-12-myristate-13-acetate response element sequences were ineffective. Electrophoretic mobility shift assays and supershift assays revealed that c-Fos-containing activator protein- complexes preferentially bound the metallothionein phorbol-12-myristate-13-acetate response element sequence-containing oligonucleotides. Furthermore, antisense oligonucleotides to c-fos and c-jun were also protective. The apoptotic death of hippocampal neurons has been hypothesized to contribute to the cognitive impairments observed following insults to the brain. While increases in intracellular calcium are thought to be key mediators of neuronal apoptosis, the biochemical cascade(s) activated as a result of increased Ca2+ which mediates apoptosis of hippocampal neurons is (are) not well understood. The findings presented in this study suggest that mobilization of internal calcium via prolonged exposure of sphingosine-1-phosphate induces apoptosis of hippocampal neurons in culture. Sustained increases in intracellular calcium activate a phosphatase cascade that includes calcineurin and a phosphatase 2A-like phosphatase, and leads to the expression of genes containing metallothionein phorbol-12-myristate-13-acetate response element (TGAGTCA)-type enhancer sequences. The expression of genes containing TGAGTCA-type enhancer sequences appears to be essential for sphingosine-1-phosphate-induced apoptosis of hippocampal neurons.

A mitogen-activated protein kinase cascade in the CA1/CA2 subfield of the dorsal hippocampus is essential for long-term spatial memory.

Behavioral, biophysical, and pharmacological studies have implicated the hippocampus in the formation and storage of spatial memory. However, the molecular mechanisms underlying long-term spatial memory are poorly understood. In this study, we show that mitogen-activated protein kinase (MAPK, also called ERK) is activated in the dorsal, but not the ventral, hippocampus of rats after training in a spatial memory task, the Morris water maze. The activation was expressed as enhanced phosphorylation of MAPK in the pyramidal neurons of the CA1/CA2 subfield. In contrast, no increase in the percentage of phospho-MAPK-positive cells was detected in either the CA3 subfield or the dentate gyrus. The enhanced phosphorylation was observed only after multiple training trials but not after a single trial or after multiple trials in which the location of the target platform was randomly changed between each trial. Inhibition of the MAPK/ERK cascade in dorsal hippocampi did not impair acquisition, but blocked the formation of long-term spatial memory. In contrast, intrahippocampal infusion of SB203580, a specific inhibitor of the stress-activated MAPK (p38 MAPK), did not interfere with memory storage. These results demonstrate a MAPK-mediated cellular event in the CA1/CA2 subfields of the dorsal hippocampus that is critical for long-term spatial memory.

Sequestration of cAMP response element-binding proteins by transcription factor decoys causes collateral elaboration of regenerating Aplysia motor neuron axons.

Axonal injury increases intracellular Ca2+ and cAMP and has been shown to induce gene expression, which is thought to be a key event for regeneration. Increases in intracellular Ca2+ and/or cAMP can alter gene expression via activation of a family of transcription factors that bind to and modulate the expression of CRE (Ca2+/cAMP response element) sequence-containing genes. We have used Aplysia motor neurons to examine the role of CRE-binding proteins in axonal regeneration after injury. We report that axonal injury increases the binding of proteins to a CRE sequence-containing probe. In addition, Western blot analysis revealed that the level of ApCREB2, a CRE sequence-binding repressor, was enhanced as a result of axonal injury. The sequestration of CRE-binding proteins by microinjection of CRE sequence-containing plasmids enhanced axon collateral formation (both number and length) as compared with control plasmid injections. These findings show that Ca2+/cAMP-mediated gene expression via CRE-binding transcription factors participates in the regeneration of motor neuron axons.

Extracellular ATP induces formation of AP-1 complexes in astrocytes via P2 purinoceptors.

The transcription activator protein-1 (AP-1) complex is a heterodimer consisting of Fos and Jun family members. We found that extracellular ATP stimulated AP-1 DNA binding activity in cerebral cortical astrocyte cultures. This activity was maximal at 1 h and persisted for at least 3 h post-treatment. Shift-Western blotting indicated the presence of c-Fos in the AP-1 complexes. Stimulation of AP-1 binding by ATP was due to activation of P2 rather than P1 purinoceptors. The protein kinase C (PKC) inhibitor Ro 31-8220 markedly reduced P2 purinoceptor-mediated AP-1 induction. The induction of AP-1 complexes by ATP may contribute to changes in gene expression which underlie the trophic effects of extracellular ATP on astrocytes.

Characterization and phosphorylation of CREB-like proteins in Aplysia central nervous system.

Studies in Aplysia californica indicate that cAMP-mediated gene expression is necessary for long-term facilitation, a correlate of long-term memory. It has been shown that blocking the expression of cAMP-inducible genes in sensory neurons impedes long-term facilitation without any effect on short-term facilitation. Specifically, blocking the binding of CREB-like proteins or inhibiting the expression of a cAMP-inducible gene, C[symbon: see text]EBP, impairs long-term facilitation. In this report, we show the presence of a family of CREB-like proteins in Aplysia CNS that specifically bind to the CRE sequence and cross-react with rat CREB antibodies. Similar to mammalian CREB proteins, Aplysia homologues interact with each other via leucine zipper domains. This interaction can be disrupted by peptides containing the CREB leucine zipper sequence. We demonstrate that a 43 kDa CREB-like protein present in CNS extracts can be phosphorylated in vitro by cAMP-dependent protein kinase A. Moreover, exposure of ganglia to serotonin (5-HT), a transmitter involved in long-term facilitation, increases the phosphorylation of this protein. This biochemical data further supports the involvement of CREB-like proteins in memory storage.