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Biomedical subjects

N Nayak

Publications and source records attributed to N Nayak.

At least 19 recordsLinked to original sources
PubMed2006

Decidual stromal cell response to paracrine signals from the trophoblast: amplification of immune and angiogenic modulators.

During the invasive phase of implantation, trophoblasts and maternal decidual stromal cells secrete products that regulate trophoblast differentiation and migration into the maternal endometrium. Paracrine interactions between the extravillous trophoblast and the maternal decidua are important for successful embryonic implantation, including establishing the placental vasculature, anchoring the placenta to the uterine wall, and promoting the immunoacceptance of the fetal allograph. To our knowledge, global crosstalk between the trophoblast and the decidua has not been elucidated to date, and the present study used a functional genomics approach to investigate these paracrine interactions. Human endometrial stromal cells were decidualized with progesterone and further treated with conditioned media from human trophoblasts (TCM) or, as a control, with control conditioned media (CCM) from nondecidualized stromal cells for 0, 3, and 12 h. Total RNA was isolated and processed for analysis on whole-genome, high-density oligonucleotide arrays containing 54,600 genes. We found that 1374 genes were significantly upregulated and that 3443 genes were significantly downregulated after 12 h of coincubation of stromal cells with TCM, compared to CCM. Among the most upregulated genes were the chemokines CXCL1 (GRO1) and IL8,CXCR4, and other genes involved in the immune response (CCL8 [SCYA8], pentraxin 3 (PTX3), IL6, and interferon-regulated and -related genes) as well as TNFAIP6 (tumor necrosis factor alpha-induced protein 6) and metalloproteinases (MMP1, MMP10, and MMP14). Among the downregulated genes were growth factors, e.g., IGF1, FGF1, TGFB1, and angiopoietin-1, and genes involved in Wnt signaling (WNT4 and FZD). Real-time RT-PCR and ELISAs, as well as immunohistochemical analysis of human placental bed specimens, confirmed these data for representative genes of both up- and downregulated groups. The data demonstrate a significant induction of proinflammatory cytokines and chemokines, as well as angiogenic/static factors in decidualized endometrial stromal cells in response to trophoblast-secreted products. The data suggest that the trophoblast acts to alter the local immune environment of the decidua to facilitate the process of implantation and ensure an enriched cytokine/chemokine environment while limiting the mitotic activity of the stromal cells during the invasive phase of implantation.

Angiogenic Proteins↗
PubMed2006

Serotype distribution of Streptococcus pneumoniae isolates from ophthalmic and systemic infections and of commensal origin.

BACKGROUND AND OBJECTIVES: Information regarding serotype distributions of Streptococcus pneumoniae causing ophthalmic infections is scanty. This study was therefore undertaken to determine the antimicrobial susceptibility status and serotypes of S. pneumoniae isolated from various ophthalmic infections and to compare with those isolated from systemic infections and commensal nasopharyngeal flora. METHODS: Thirty eight of S. pneumoniae isolates from ophthalmic infections, 9 from systemic infections and 14 from the nasopharynx of apparently healthy school children were biochemically characterized and tested for in vitro antimicrobial susceptibility to various antibiotics. Serotyping of these 61 isolates was done by a rapid co-agglutination method. RESULTS: All the 61 isolates were sensitive to oxacillin (penicillin) and susceptibility against other antimicrobials was variable. No multidrug resistance was observed. The 38 ophthalmic isolates were distributed in 15 different serotypes. Most prevalent serotypes were 14, followed by 8 and 19F. The 9 systemic and 14 commensal. isolates of S. pneumoniae were distributed in 7 and 11 serotypes respectively. Three of the systemic and six of the commensal serotypes were observed in ophthalmic infections whereas four of the commensal serotypes were observed in systemic infections. INTERPRETATION AND CONCLUSION: Resistance to penicillin was not observed. In ophthalmic infections, a wide range of serotypes of S. pneumoniae were observed. More than half of the commensal serotypes obtained in the study as well as majority of the systemic serotypes were observed in ophthalmic infections.

Adolescent↗
PubMed2005

Lead in paint and soil in Karnataka and Gujarat, India.

Blood lead surveys in several areas of India have found very high percentages of children with elevated blood lead levels. Fifty-three percent of children under 12 years of age in a seven-city screening had blood lead levels equal to or greater than 10 microg/dL, the level currently considered elevated by the U.S. Centers for Disease Control and Prevention (CDC). A number of these surveys focused on populations near lead smelters or in areas with high lead levels from combustion of lead-containing gasoline. There is little information available, however, on the levels of lead in paint in India and in soil. Field portable X-ray fluorescence analyzers were used to determine environmental lead levels in paint, dust, air, soil, and other bulk samples near several lead-using industries and in the residential environments of children with very high blood lead levels, at least four times as high as the CDC limit. Soils near industrial operations, such as secondary lead smelters, and battery dismantling units contained levels up to 100,000 ppm of lead. Four of 29 currently available paints from five manufacturers measured 1.0 mg/cm2 or above--the current U.S. definition of lead-based paint in housing-after the application of a single coat; four others measured at least 1.0 after three coats, and three others likely reached this level after the application of an additional one or two coats. In 5 of 10 homes of the elevated blood lead children, three or more locations in or around the home were found to have lead paint levels of 1.0 mg/cm2 or higher. Soil exceeding the U.S. standard for residential areas (400 ppm) was found at only one of the houses. Other sources of lead exposure, including traditional ayurvedic medicine tablets, were also observed. Similar surveys would be useful elsewhere in India and in other developing countries.

Data Collection↗
PubMed2004

Portable lead analyzer to locate source of lead.

OBJECTIVE: To investigate the sources of lead in the environment in children with elevated blood, with the help of a Field Portable X-Ray Fluorescence Analyzer. METHODS: One hundred and seven school children were chosen for this study on a random basis, from Mangalore and Karnataka. Their blood lead was analyzed. Of the cases analyzed, 10 students whose blood lead level was more than 40 microg/dl were investigated using a field portable X-Ray Fluorescence Analyzer. This is the first time such a device has been available for this purpose in India. RESULTS: The 'likely' source of lead exposure could be determined in eight cases which was from the immediate environment of the children like 'lead-based' paint on surfaces in the house, on playground and other exterior equipment; lead storage batteries, contaminated dust and soil and other lead-containing substances. CONCLUSION: The use of an X-Ray Fluorescence Analyser appeared to be useful in determining the source of lead.

Child↗
PubMed2001

Retinyl ester secretion by intestinal cells: a specific and regulated process dependent on assembly and secretion of chylomicrons.

Retinyl esters (RE) have been used extensively as markers to study chylomicron (CM) catabolism because they are secreted in the postprandial state with CM and do not exchange with other lipoproteins in the plasma. To understand the mechanism of secretion of RE by the intestine under the fasting and postprandial states, differentiated Caco-2 cells were supplemented with radiolabeled retinol under conditions that support or do not support CM secretion. We observed that these cells assimilate vitamin A by a rapid uptake mechanism. After uptake, cells store retinol in both esterified and unesterified forms. Under fasting conditions, cells do not secrete RE but secrete free retinol unassociated with lipoproteins. Under postprandial conditions, cells secrete significant amounts of RE only with CM. The secretion of RE with CM was independent of the rate of uptake of retinol and intracellular free and esterified retinol levels, and was absolutely dependent on the assembly and secretion of CM. The secretion of RE was correlated with the secretion of CM and not with the secretion of total apolipoprotein B. Inhibition of CM secretion by Pluronic L81 decreased the secretion of RE and did not result in their increased secretion with smaller lipoproteins. These data strongly suggest that RE secretion by the intestinal cells is a specific and regulated process that occurs in the postprandial state and is dependent on the assembly and secretion of CM. We propose that RE are added to CM during final stages of lipoprotein assembly and may serve as signposts for these steps.

Caco-2 Cells↗
PubMed2001

A simple alternative method for rapid detection of slime produced by Staphylococcus epidermidis isolates in bacterial keratitis.

BACKGROUND & OBJECTIVES: Slime is a known virulence factor of Staphylococcus epidermidis. The conventional Christensen's method for detection of slime in the laboratory takes at least 48 h. We, therefore, tried to evaluate the efficacy of the Congo red agar method as a routine procedure for detecting slime among isolates from corneal ulcers. METHODS: A total of 244 isolates from corneal ulcers were identified as S. epidermidis by the standard procedures. Slime was detected both by the conventional Christensen's method as well as by the Congo red agar method. RESULTS: Ninety two (37.7%) isolates were positive and 86 (35.2%) were negative for slime by both the techniques. Fifty four (22.1%) isolates were positive in Congo red agar, but negative by Christensen's method; whereas only 12 (4.9%) were negative by Congo red but positive by Christensen's method. Detection of slime by Congo red agar method was rapid i.e., all the 146 strains were positive within 24 h of incubation. On the other hand, Christensen's method had a delayed response; 42.3 per cent (44/104) strains being negative during the first 24 h of incubation. INTERPRETATION & CONCLUSION: Our results suggested that culture on Congo red agar was a sensitive and rapid test for detecting slime. This might help in the quick identification in a routine laboratory of slime positive isolates in bacterial keratitis.

Bacteriological Techniques↗
PubMed2000

Anti-restenotic effect of copper-62 liquid-filled balloon in porcine coronary arteries: novel use of a short half-life positron emitter.

PURPOSE: To determine the efficacy of the use of copper-62, a positron emitter with a half-life of 9.7 minutes, as an intracoronary brachytherapy (IRBT) source in the prevention of neointima formation (NF) following overstretch balloon injury (BI) in the porcine model. METHODS AND MATERIALS: Sixteen swine were treated after BI to their left anterior descending (LAD), left circumflex (LCX), and/or right coronary artery (RCA). Twelve of the injured arteries received placebo and 10 received 25 Gy, delivered to 0.5 mm from the surface of the treatment balloon filled with liquid (62)Cu. Dosimetry was based on Monte Carlo calculations. Two weeks after treatment, the animals were sacrificed, and the treated coronaries were perfusion-fixed and stained. Intimal area (IA) and medial fracture length (FL) were analyzed by computer-aided histomorphometry. RESULTS: The ((62)Zn/(62)Cu) generator, together with a rapid concentration process, was successful in delivering the short-lived (62)Cu at the high concentration required for intravascular brachytherapy (IVBT). The fracture length in the two groups was similar (2.10 +/- 0.57; 2.02 +/- 0.77; p = NS). Arteries studied showed significant reduction in NF (IA: 0.23 +/- 0.47 mm(2) vs. 1.08 +/- 0.57 mm(2); p < 0.01. IA/FL = 0.09 +/- 0.17 mm vs. 0.51 +/- 0.21 mm; p < 0.01). CONCLUSIONS: This study demonstrated that use of liquid (62)Cu as an IVBT source is safe and feasible. All 16 swine tolerated the treatment well with no radiation-induced side effects or symptoms throughout the 2-week period. The isotope delivered the dose necessary to inhibit NF in the porcine coronary BI model.

Animals↗
PubMed2000

Decreased secretion of ApoB follows inhibition of ApoB-MTP binding by a novel antagonist.

Apolipoprotein B (apoB) and microsomal triglyceride transfer protein (MTP) are essential for the efficient assembly of triglyceride-rich lipoproteins. Evidence has been presented for physical interactions between these proteins. To study the importance of apoB-MTP binding in apoB secretion, we have identified a compound, AGI-S17, that inhibited (60-70% at 40 microM) the binding of various apoB peptides to MTP but not to an anti-apoB monoclonal antibody, 1D1, whose epitope overlaps with an MTP binding site in apoB. AGI-S17 had no significant effect on the lipid transfer activity of the purified MTP. In contrast, another antagonist, BMS-200150, did not affect apoB-MTP binding but inhibited MTP's lipid transfer activity. The differential effects of these inhibitors suggest two functionally independent, apoB binding and lipid transfer, domains in MTP. AGI-S17 was then used to study its effect on the lipid transfer and apoB binding activities of MTP in HepG2 cells. AGI-S17 had no effect on cellular lipid transfer activities, but it inhibited coimmunoprecipitation of apoB with MTP. These studies indicate that AGI-S17 inhibits apoB-MTP binding but has no effect on MTP's lipid transfer activity. Experiments were then performed to study the effect of inhibition of apoB-MTP binding on apoB secretion in HepG2 cells. AGI-S17 (40 microM) did not affect cell protein levels but decreased the total mass of apoB secreted by 70-85%. Similarly, AGI-S17 inhibited the secretion of nascent apoB by 60-80%, but did not affect albumin secretion. These studies indicate that AGI-S17 decreases apoB secretion most likely by inhibiting apoB-MTP interactions. Thus, the binding of MTP to apoB may be important for the assembly and secretion of apoB-containing lipoproteins and can be a potential target for the development of lipid-lowering drugs. It is proposed that the apoB binding may represent MTP's chaperone activity that assists in the transfer from the membrane to the lumen of the endoplasmic reticulum and in the net lipidation of nascent apoB, and may be essential for lipoprotein assembly and secretion.

Albumins↗
PubMed2000

Performance of a 62Zn/62Cu generator in clinical trials of PET perfusion agent 62Cu-PTSM.

UNLABELLED: The 62Zn/62Cu PET generator can be inexpensively produced and distributed from a single production site operating under typical good manufacturing practice guidelines. It therefore has the potential to greatly facilitate development of clinically practical PET. We report generator performance in a study in which 62Cu-pyruvaldehyde-bis(n4-methylthiosemicarbazone (PTSM) myocardial perfusion imaging is compared with 99mTc-sestamibi in the diagnosis of coronary artery disease. The 62Zn/62Cu generator is an improved version of a previously reported system that employs automated synthesis of 62Cu-PTSM. With this approach, the cumbersome step of 18C purification has been eliminated. METHODS: The 62Zn (9.3 h half-life) parent isotope is prepared by proton bombardment of natural copper at 33 MeV. A typical target irradiated with 37.5 microA/h is delivered by 12:00 PM on the day it is to be processed. Purified 62Zn obtained from the target is loaded onto the generator column in 2 mol/L HCl. The generator is eluted using an internal three-channel peristaltic pump, which delivers 2.25 mL eluant (1.8 mol/L NaCl, 0.2 mol/L HCl) through the generator column to elute the 62Cu in 40 s. The same pump simultaneously pumps an equal volume of buffer (0.4 mol/L NaOAc) and 1 mL ligand solution (2 ppm PTSM, 2% EtOH) passing it through a septum into a 35-cc syringe preloaded with 28 mL sterile water. This solution is thoroughly mixed by agitation of the syringe and injected as a bolus through a 0.2 microm filter. The generator is eluted twice before shipping, providing quality assurance samples, and shipped to the clinical site by overnight delivery. Complete quality assurance testing is performed the evening before the generator reaches the clinical site. RESULTS: A total of 34 generators have been produced and shipped to 2 clinical sites for a phase III Food and Drug Administration study. The load activity on the generators at 8:00 AM the day of clinical use was 1.7+/-0.2 GBq (46.7+/-5.6 mCi), and yield was 72%+/-16%. Breakthrough of 62Zn was undetectable by high-purity germanium spectroscopy for all units. Radiochemical purity was 95.4%+/-2.4%. Volume delivered, pH, sterility, and bacterial endotoxin tests yielded passing results on all generators. The entire process of generator production, from target receipt to generator shipment, took less than 6 h and cost approximately $1000, including shipping charges and cyclotron cost. A total of 68 patients were injected with 2 62Cu-PTSM doses, with a mean injected activity of 0.8+/-0.2 GBq (20.5+/-5.3 mCi) with no adverse side effects. CONCLUSION: Results of this work confirm that the 62Zn/62Cu generator is an easily produced, transportable, and inexpensive source of PET radiopharmaceuticals, which can expand the field of clinical PET imaging by providing radiopharmaceuticals to sites not associated with cyclotrons.

Clinical Trials, Phase III as Topic↗
PubMed2000

Slime production as a virulence factor in Staphylococcus epidermidis isolated from bacterial keratitis.

A total of 126 coagulase negative staphylococci (CONS) isolated from corneal scrapings of patients of bacterial keratitis and 50 isolates from healthy eyes (controls) were tested for slime production. Eighty eight (69.84%) of 126 isolates from patients and 11 (22%) of 50 isolates from controls were slime producing (P < 0.001). Of these 88 isolates, 42 were Staphylococcus epidermidis biotype II, 30 were S. epidermidis biotype I, 8 were S. epidermidis biotype III and the rest belonged to CONS other than S. epidermidis. Amongst the corneal ulcer isolates, multidrug resistance (resistance to 3 or more antibiotics) was observed in 82.9 per cent (73/88) slime producing organisms as against only 18.4 per cent (7/38) nonslime producing organisms (P < 0.001). Similarly, of the total 99 slime positive and 77 slime negative isolates, 79 (79.8%) and 22 (28.6%) respectively were multidrug resistant (P < 0.001). Although, slime production is known to be one of the major virulence factors of CONS in extraocular systemic staphylococcal infections, the present study detected slime in isolates from ocular infections. It was found that S. epidermidis I and II were the common biotypes associated with bacterial keratitis and, slime production and multidrug resistance were the two important virulence factors. These observations have clinical and therapeutic significance.

Eye Infections, Bacterial↗
PubMed1999

A convenient microscale colorimetric method for terminal galactose on immunoglobulins.

A new approach for quantitative determination of terminal galactose (Gal) residues of immunoglobulins was developed by combining exoglycosidase digestion with the classical colorimetric estimation of reducing sugars. The ferricyanide colorimetric method was modified to increase the stability of the chromophore (Prussian blue) and adapted to determine the amount of terminal Gal residues present in immunoglobulins. The method involves the release of covalently bound Gal from immunoglobulins by Diplococcus pneumoniae beta-D-galactosidase (specific for beta(1,4) linked galactose), removal of the glycoprotein and enzyme from the reaction mixture by heat denaturation or ethanol precipitation, followed by colorimetric measurement of the released sugar using the ferricyanide assay. The ferricyanide method was modified to enhance the solubility and stability of the chromophore by increasing the concentration of aqueous sulfuric acid and sodium dodecyl sulfate (SDS). The linear range of the modified method was from approximately 11 to 111 microM Gal. Typical variation in assay results was on the order of 5%. Using the modified method, the terminal Gal content of a recombinant chimeric monoclonal antibody (anti-CD20, rIgG) expressed in Chinese hamster ovary (CHO) cells was determined and evaluated for batch-to-batch consistency. The method was used to optimize pH, time, temperature, and enzyme concentration for beta-galactosidase digestion for maximal release of terminal Gal residues from rIgG.

Animals↗
PubMed1999

Automated exchange transfusion for life-threatening plasmodium falciparum malaria--lessons relating to prophylaxis and treatment.

We report a case of traveller to Kenya who contracted severe plasmodium falciparum malaria complicated by disseminated intravascular coagulation and acute renal failure. She had taken no antimalarial prophylaxis in view of concerns in the media regarding the adverse effects of mefloquine. There was a protracted delay before the diagnosis of malaria was made. Clinical recovery occurred following treatment with intravenous quinine, haemofiltration and manual/automated red-cell exchange transfusions. Automated red-cell exchange transfusion resulted in a marked decrease in the parasitaemia, before a response to quinine therapy would have been anticipated, leading to a successful outcome thereafter. In conjunction with other groups we therefore feel that exchange transfusions should be considered in seriously ill patients with falciparum malaria, multiorgan complications and parasitaemias greater than 10%.

Adult↗