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Biomedical subjects

M Ray

Publications and source records attributed to M Ray.

At least 37 records · Page 2Linked to original sources

Antinociceptive activity of a neurosteroid tetrahydrodeoxycorticosterone (5alpha-pregnan-3alpha-21-diol-20-one) and its possible mechanism(s) of action.

The present study investigates the effects of a neurosteroid tetrahydrodeoxycorticosterone (5alpha-pregnan-3alpha-21-diol-20-one) in two experimental models of pain sensitivity in mice. Tetrahydrodeoxycorticosterone (2.5, 5 mg/kg, i.p.) dose dependently decreased the licking response in formalin test and increased the tail flick latency (TFL) in tail flick test. Bicuculline (2 mg/kg, i.p.), a GABA(A) receptor antagonist blocked the antinociceptive effect of tetrahydrodeoxycorticosterone in TFL test but failed to modulate licking response in formalin test. Naloxone (1 mg/kg, i.p.), an opioid antagonist effectively attenuated the analgesic effect of tetrahydrodeoxycorticosterone in both the models. Tetrahydrodeoxycorticosterone pretreatment potentiated the antinociceptive response of morphine, an opioid compound and nimodipine, a calcium channel blocker in formalin as well as TFL test. Thus, tetrahydrodeoxycorticosterone exerts an analgesic effect, which may be mediated by modulating GABA-ergic and/or opioid-ergic mechanisms and voltage-gated calcium channels.

Analgesics↗

Synthesis and characterization of pyridine amide cation radical complexes of iron: stabilization due to coordination with low-spin iron(III) center.

We reported the synthesis and characterization of peptide complexes of low-spin iron(III) [Fe(bpb)(py)2][ClO4] (1) and Na[Fe(bpb)(CN)2] (2) [H2bpb = 1,2-bis(pyridine-2-carboxamido)benzene; py = pyridine], where iron is coordinated to four nitrogen donors in the equatorial plane with two amide nitrogen anions and two pyridine nitrogen donors (Ray, M.; Mukherjee, R.; Richardson, J. F.; Buchanan, R. M. J. Chem. Soc., Dalton Trans. 1993, 2451). Chemical oxidation of 2 and a new low-spin iron(III) complex Na[Fe(Me6bpb)(CN)2].H2O (4) [synthesized from a new iron(III) complex [Fe(Me6bpb)(py)2][ClO4] (3) (S = 1/2)] [H2Me6bpb = 1,2-bis(3,5-dimethylpyridine2-carboxamido)-4,5-dimethylbenzene) by (NH4)2Ce(NO3)6 afforded isolation of two novel complexes [Fe(bpb)-(CN)2] (5) and [Fe(Me6bpb)(CN)2].H2O (6). All the complexes have been characterized by physicochemical techniques. While 1-4 are brown/green, 5 and 6 are violet/bluish violet. The collective evidence from infrared, electronic, Mössbauer, and 1H NMR spectroscopies, from temperature-dependent magnetic susceptibility data, and from cyclic voltammetric studies provides unambiguous evidence that 5 and 6 are low-spin iron(III) ligand cation radical complexes rather than iron(IV) complexes. Cyclic voltammetric studies on isolated oxidized complexes 5 and 6 display identical behavior (a metal-centered reduction and a ligand-centered oxidation) to that observed for complexes 2 and 4, respectively. The Mössbauer data for 6 are almost identical with those of the parent compound 4, providing compelling evidence that oxidation has occurred at the ligand in a site remote from the iron atom. Strong antiferromagnetic coupling (-2J > or = 450 cm(-1)) of the S = 1/2 iron atom with the S = 1/2 ligand pi-cation radical leads to an effectively S = 0 ground state of 5 and 6. The oxidized complexes display 1H NMR spectra (in CDCl3 solution), characteristic of diamagnetic species.

Journal Article↗

The hamster heart: a paradox in itself.

Perfusion of all mammalian heart muscle except hamster with Ca(2+)-free Tyrode and thereafter reperfusion with normal Tyrode causes irreversible damage, the calcium paradox. Our study aims at deciphering the role of creatine kinase, high energy phosphates and Ca(2+)influx in the genesis of myocardial injury in the rat and comparing it with the hamster. Isolated hearts from hamster and rats were perfused in the Langendorff mode at 37 degrees C for 30 min with normal Tyrode, for 15 min with Ca(2+)-free Tyrode and thereafter for 30 min of reperfusion with normal Tyrode. The 'high energy phosphate compound' levels were monitored by(31)P-NMR, creatine kinase (CK) release was measured in the perfusate.(45)Ca influx was estimated in the papillary muscle. We observed that in the rat heart: (a) high energy phosphate levels declined significantly within 1 min of Ca(2+)reperfusion; (b) a massive release of CK occurred upon Ca(2+)reperfusion; (c) there was a significant increase of Ca(2+)influx. In the hamster heart, there was preservation of high energy phosphates, CK release was prevented completely and no rise in(45)Ca influx was observed upon Ca(2+)reperfusion. These results suggest that the hamster heart has a remarkable capacity for Ca(2+)homeostasis which protects the heart from Ca(2+)overload.

Adenosine Diphosphate↗

The hamster heart is resistant to calcium paradox.

Reintroduction of Ca(2+)or modification of internal Ca(2+)stores by caffeine results in widespread irreversible injury. The adult golden hamster, however, is immune to such insult and the present report investigates the phenomenon. Isolated Langendorff perfused hamster and rat heart were subjected to 15 min Ca(2+)-free perfusion followed by 30 min of Ca(2+)perfusion at 37 degrees C. Caffeine was introduced during Ca(2+)-free perfusion in a number of experiments. Papillary muscles were processed for the ultra-structural study. The hamster heart did not exhibit the calcium paradox state whereas rat heart did. Hamster heart treated with caffeine either throughout or 5 min after starting Ca(2+)-free perfusion showed 70%+/-8 or 65%+/-8. 42 recovery, respectively, when Ca(2+)reperfusion was performed. Ultrastructure of muscle from both groups showed relaxed myocytes with slight disorientation of the sarcomere register. This disorientation was not seen in hamster hearts undergoing the conventional calcium paradox protocol. The hamster cardiac muscle is remarkably tolerant to [Ca(2+)]()i loading either induced by Ca(2+)reperfusion or caffeine-induced sarcoplasmic reticulum Ca(2+)release. Structural and functional characterization of Ca(2+)depletion and repletion in the hamster heart have been discussed.

Animals↗

Granulocyte macrophage-colony stimulating factor (GM-CSF) in neonatal neutropenia.

Neutropenia in neonates is often associated with sepsis, prematurity and maternal hypertension with increased risk of mortality. We describe two neonates with neutropenia treated with granulocyte macrophage colony stimulating factor. The total and absolute neutrophil counts showed a marked response and led to a favourable outcome. Human granulocyte macrophage colony stimulating factor may be used as an adjuvant therapy for neonatal neutropenia of different aetiologies.

Granulocyte-Macrophage Colony-Stimulating Factor↗

Inhibition of interferon-gamma signaling by Leishmania donovani.

Leishmania infection causes marked down-regulation of interferon (IFN)-gamma-induced gene activity in macrophages, but the mechanism of the blockade has not been fully defined. The IFN-gamma signal transduction pathway was analyzed in Leishmania donovani-infected phorbol-differentiated U937 human promonocytic cells. IFN-gamma stimulation induced marked phosphorylation of its own receptor (IFN-gammaR)-alpha chain. Phosphorylation of the receptor subunit was significantly inhibited after 24 h of infection with the parasite, apparently because of decreased amounts of the receptor subunit. Formation of the IFN-gammaR complex, as assessed by tyrosine phosphorylation and association of Jak2, was strongly inhibited in cells infected for 24 h. Inhibition of the IFN-gammaR complex formation correlated with inhibition of STAT1alpha binding to the IFN-gamma response region. Pretreatment with purified parasite lipophosphoglycan before IFN-gamma stimulation had no effect on tyrosine phosphorylation. Thus, inhibition of tyrosine phosphorylation of the IFN-gammaR-alpha chain and subsequent signal transduction are most likely due to the decreased amount of IFN-gammaR-alpha protein after infection.

Animals↗

High-affinity maltose binding and transport by the thermophilic anaerobe Thermoanaerobacter ethanolicus 39E.

Thermoanaerobacter ethanolicus is a gram-positive thermophile that produces considerable amounts of ethanol from soluble sugars and polymeric substrates, including starch. Growth on maltose, a product of starch hydrolysis, was associated with the production of a prominent membrane-associated protein that had an apparent molecular weight of 43,800 and was not detected in cells grown on xylose or glucose. Filter-binding assays revealed that cell membranes bound maltose with high affinity. Metabolic labeling of T. ethanolicus maltose-grown cells with [(14)C]palmitic acid showed that this protein was posttranslationally acylated. A maltose-binding protein was purified by using an amylose resin affinity column, and the binding constant was 270 nM. Since maltase activity was found only in the cytosol of fractionated cells and unlabeled glucose did not compete with radiolabeled maltose for uptake in whole cells, it appeared that maltose was transported intact. In whole-cell transport assays, the affinity for maltose was approximately 40 nM. Maltotriose and alpha-trehalose competitively inhibited maltose uptake in transport assays, whereas glucose, cellobiose, and a range of disaccharides had little effect. Based on these results, it appears that T. ethanolicus possesses a high-affinity, ABC type transport system that is specific for maltose, maltotriose, and alpha-trehalose.

Amino Acid Sequence↗

Clinical spectrum of 500 children with neurocysticercosis and response to albendazole therapy.

Neurocysticercosis is a major cause of neurologic illness worldwide. Its manifestations are variable, and somewhat different when it occurs in children. Controversy exists regarding anticysticercal therapy. The clinical, laboratory, and radiographic features of 500 consecutive children with neurocysticercosis were studied; the children were then followed prospectively and their response to albendazole therapy was analyzed. Diagnosis of neurocysticercosis was based primarily on neuroimaging. Computed tomographic (CT) scans, neurocysticercosis serology, chest radiographs, and Mantoux tests were done in all children, and magnetic resonance imaging scans in 10%. All children with multiple lesions, and some randomly allocated children with single, small, enhancing CT lesions received albendazole. CT scans were repeated after 3 to 6 months. There were 272 boys and 228 girls, age range 1 6/12 to 12 6/12 years. Seizures were present in 94.8% of cases; 83.7% had focal seizures. Features of raised intracranial pressure were seen in 30% of patients and focal neurodeficit in 4%. Single lesions were seen in 76% of the children, with perilesional edema in 57.4%. Thirty-four children who had multiple cysts and received albendazole underwent serial CT evaluation. Four showed disappearance of lesions and 22 had reductions in the size or number, to give an overall improvement rate of 76%. Serial CT studies were available on 176 children with single lesions, 90 of whom received albendazole. Improvement (disappearance or reduction in the size of lesions) was observed in 91% (82 of 90) of albendazole-treated children versus 85% (73 of 86) of untreated children. This difference was not significant. No significant side-effects of albendazole were reported. These data indicate that partial seizures and single parenchymal cysts are the most frequent clinical and neuroradiographic manifestations of neurocysticercosis in children. Although albendazole therapy should be considered, especially in children with multiple lesions, many children with isolated neurocysticercosis will improve without antiparasitic therapy.

Albendazole↗

Scoring of skin rejection in a swine composite tissue allograft model.

BACKGROUND: For the first time, we define and correlate visual and histologic grading systems of composite tissue allograft (CTA) skin rejection in a large-animal model and determine the utility of these grading systems for early diagnosis and monitoring of rejection. MATERIALS AND METHODS: Sixteen pairs of outbred swine underwent transplant of a forelimb osteomyocutaneous free flap. Group I (n = 6) did not receive immunosuppressive therapy. Group II (n = 10) received oral cyclosporin A, mycophenolate mofetil, and prednisone. The flap was visually inspected and protocol skin biopsies were taken at frequent intervals over a 90-day period. Visual Grades 0 (no rejection) to 4 (severe rejection) were assigned based on skin color, bleeding from biopsy site, and blister formation. Histologic Grades 0 to 4 were assigned based on the degree of vasculitis, folliculitis, dermal inflammation, and epidermal degeneration present. RESULTS: All Group I animals progressively rejected their graft by Day 7. Group II grafts survived from 19 and 90 days; 93% of 115 biopsy specimens were read to be within +/-1 histologic score of their assigned flap visual grade. Visual assessment carried an 8% false positive and 39% false negative rate with regard to biopsy-proven rejection. However, 81% of missed rejection specimens were histologic Grade 1. Biopsy, when visually indicated, would detect all rejection episodes when histologically Grade 1 or 2 and still potentially reversible. CONCLUSIONS: Visual scoring of CTA skin serves as a useful tool for initially detecting rejection, but repeated histologic evaluation is necessary for monitoring the subsequent course of the graft.

Animals↗

Focal seizures with single small ring-enhancing lesion.

An 8-year-old girl presented with simple partial seizures. The differential diagnosis and evaluation point out the fact that in most of the world, conditions considered rare in the United States are important diagnostic considerations.

Acute Disease↗

Glyceraldehyde-3-phosphate dehydrogenase from Ehrlich ascites carcinoma cells its possible role in the high glycolysis of malignant cells.

Glyceraldehyde-3-phosphate dehydrogenase has been purified to apparent homogeneity from Ehrlich ascites carcinoma (EAC) cells. The enzyme is quite active over a pH range of 7.5-9.0 with an optimum pH of 8.4-8.7. The specific activity of the enzyme is much higher than that from other normal sources. In contrast to enzyme obtained from rabbit muscle, the EAC cell enzyme is not significantly inhibited by physiological concentrations of ATP at physiological pH. Kinetic studies using different substrates and inhibitors indicate that the properties of the EAC cell enzyme are significantly different from those of glyceraldehyde-3-phosphate dehydrogenase obtained from other normal sources. The striking dissimilarity of the malignant cell glyceraldehyde-3-phosphate dehydrogenase compared with this enzyme from other normal sources, particularly in respect to the interaction with ATP, may in part explain the high glycolysis of malignant cells.

Adenosine Triphosphate↗

Deep lamellar keratoplasty versus penetrating keratoplasty for corneal lesions.

PURPOSE: To compare the effectiveness of deep lamellar keratoplasty (DLK) with that of penetrating keratoplasty (PKP) in cases of corneal lesions not involving the endothelium. METHODS: Forty-eight eyes with leukomatous corneal opacity (n = 33), keratoconus with apical scarring (n = 6), granular corneal dystrophy (n = 5), lattice corneal dystrophy (n = 2), and multiple corneal foreign bodies (n = 2) in an age group varying from 16 to 53 years underwent DLK (n = 24) and PKP (n = 24) by utilizing B and (B+ and A) grade M-K preserved donor tissue, respectively. The patients were followed up closely, and the graft clarity, visual achievement, astigmatism and endothelial cell count were evaluated at repeated occasions up to 1 year. RESULTS: Astigmatism of <3 diopters (D) and > or = 5D was obtained in 19 eyes and one eye, respectively, after DLK at 6 months, whereas six eyes of the PKP group had astigmatism <3D, and 12 eyes had > or = 5D at the end of 6 months. The same at 1 year was observed in 20 and one eye in the DLK and eight and five eyes of the PKP group. Astigmatism of > or = 5D at the end of 6 months in both the groups showed highly significant changes (p < 0.001). Best corrected visual acuity of 6/18 or more was achieved in 18 and 12 eyes at 6 months after DLK and PKP, respectively, which were statistically highly significant (p < 0.001), whereas at 1 year, it was seen in 17 and 15 eyes of the DLK and PKP groups, respectively, which was nonsignificant. The mean endothelial cell count was 2,233.3+/-64.453 cells/mm2 and 2,219.6+/-102.48 cells/mm2 at 6 months and I year, respectively, after DLK, which was nonsignificant. The mean cell count of the donor eyes used for PKP was 2,191+/-52.164 cells/mm2, 1,902.8+/-70.346 cells/mm2 at 6 months, and 1,579.0+/-80.24 cells/mm2 at 1 year. All the values showed highly significant changes (p < 0.001). Further, the graft clarity of > or = 3+ was achieved in 20 and 18 eyes at 6 months postoperatively in the DLK and PKP groups, whereas the same was observed in 19 and 13 eyes of both the groups, respectively, at 1-year follow-up. CONCLUSION: DLK is a promising procedure and should be practiced more frequently for corneal pathology not involving the endothelium.

Adolescent↗

Second laryngeal cancers in previously treated larynges.

OBJECTIVES: To review the management and outcome of patients with new second primary cases of laryngeal cancer occurring more than 3 years after the initial cancer was treated. STUDY DESIGN: Retrospective review of 855 patients with newly diagnosed and treated laryngeal cancers. METHODS: Charts were reviewed and tabulated for occurrence of second primary laryngeal tumors, method of treatment for the index and second primary laryngeal tumors, and effect of smoking status or cessation of smoking. RESULTS: Of the 855 patients, 532 patients retained their larynx; of these 377 lived more than 3 years and thus were at risk for a second new primary cancer. Of these 377 patients at risk, 19 or 5.1% developed second primary tumors. The rate of second primary disease was lower in patients whose index laryngeal cancer was treated by irradiation (4.3%) compared with those treated surgically (9.2%). However, surgical treatment of second primary laryngeal tumors resulted in far higher rates of laryngeal voicing (82%) compared with irradiation (33%). CONCLUSION: When possible, management of the index primary tumor by endoscopic resection has resulted in the highest future retention of laryngeal speech, leaving all treatment options available should a second laryngeal cancer occur. Lifelong follow-up of patients with laryngeal cancer for secondary primary tumors is important. Second primary tumors were equally distributed between patients who continued to smoke and ceased to smoke after their index primary lesion was diagnosed.

Carcinoma, Squamous Cell↗

Long-term survival of an extremity composite tissue allograft with FK506-mycophenolate mofetil therapy.

BACKGROUND: High-dose tacrolimus (FK506) monotherapy has significantly prolonged rat hindlimb allograft survival. With an eye toward direct clinical application, we used a large-animal extremity composite tissue allograft model to assess the antirejection efficacy and systemic toxicity of combination FK506-mycophenolate mofetil (MMF) treatment. METHODS: Radial forelimb osteomyocutaneous flap transplants were performed between size-matched outbred pigs assigned to one of two groups: 5 control pigs received no immunosuppression and 9 animals received a once-daily oral FK506-MMF-prednisone regimen. Rejection was assessed by visual inspection of flap skin and was correlated with serial histopathologic examination of skin biopsy specimens. RESULTS: In all control pigs the flap was completely rejected on day 7. Of the 9 pigs receiving treatment, 3 died from pneumonia on days 29, 30, and 83 without signs of rejection and another died from gastric rupture on day 42 with persistent mild rejection. The remaining 5 animals were free of rejection at the end of the 90-day follow-up period (P < 0.005 vs controls). Overall, 5 pigs had pneumonia, 4 septic arthritis, 3 toe abscesses, and 5 diarrhea and decreased weight gain. CONCLUSIONS: Combination oral FK506-MMF treatment provided a superior antirejection effect but more produced more toxicity than that previously demonstrated with cyclosporin A-MMF therapy in our model. Our results suggest that reduction of FK506 or MMF doses might decrease both infectious and drug-specific side effects while still providing adequate prophylaxis against rejection.

Animals↗

Risk factors for pediatric presumed microbial keratitis: a case-control study.

PURPOSE: To evaluate risk factors for pediatric presumed microbial keratitis and to describe the clinical picture, microbiologic spectrum, treatment modalities, posttreatment sequelae, and visual outcome in cases of pediatric presumed microbial keratitis. METHODS: A case-control study design was used to identify the risk factors associated with pediatric presumed microbial keratitis. Fifty cases of fresh corneal ulceration aged 12 years or younger were compared with 50 controls. The study variables included were age, gender, immunization status, nutritional status (weight for height), and socioeconomic status. The clinical presentation of the cases with corneal ulceration, microbiologic spectrum, and treatment modalities also were evaluated. All the cases were followed up for a minimum of 3 months, and the posttreatment sequelae and visual outcome were analyzed. RESULTS: The mean (+/- standard deviation) age of children with corneal ulceration and controls was 4.8 (+/-3.8) years and 5.1 (+/-2.8) years, respectively. Incomplete immunization status (AOR [95% confidence interval (CI)], 1.34 [0.62-2.9]) and poor nutritional status [AOR (95% CI) 1.06 (0.68-1.6)] were not found to be the predictors of corneal ulceration. Lower socioeconomic status was significantly associated with the occurrence of corneal ulceration [AOR (95% CI) 1.52 (1.1-2.3)]. Corneal trauma (38%) and systemic illness (24%) were the most often associated predisposing factors. Seventy percent of the cases were culture positive. Staphylococcus (70%) species was the most frequently isolated, followed by Pseudomonas aeruginosa (10%). Fungi were isolated in five eyes. Postresolution visual acuity at 3 months could be recorded only in 31 eyes and a visual acuity of 6/18 or better was achieved in 22% of these cases. CONCLUSION: Corneal ulceration in pediatric age group in India is associated with poverty.

Body Height↗