Biomedical subjects
Publications and source records attributed to A K Sinha.
Phytochemical investigation of the leaves of Bidens pilosa lead to the isolation and characterization of a new disubstituted acetylacetone (1) named as 3-Propyl-3-(2,4,5-trimethoxy)benzyloxy-pentan-2,4-dione.
Microwave assisted condensation of asaronaldehyde (2) with malonic acid in piperidine-AcOH provides 2,4,5-trimethoxycinnamic acid (3) in 87% yield within 4 min, which upon further reduction with PdCl2- HCOOH-aq. NaOH gives 3-(2,4,5-trimethoxy)phenyl propionic acid (4) in 88% yield within 3 min. Esterification of 4 with MeOH-H+ gives methyl 2,4,5-trimethoxyphenylpropionate (1), a metabolite of Cordia alliodora, in 94% yield within 3 min (overall 69% yield).
Extracellular invertase is the key enzyme of an apoplasmic phloem unloading pathway and catalyses the hydrolytic cleavage of the transport sugar sucrose released into the apoplast. This mechanism contributes to long-distance assimilate transport, provides the substrate to sustain heterotrophic growth and generates metabolic signals known to effect various processes of primary metabolism and defence responses. The essential function of extracellular invertase for supplying carbohydrates to sink organs was demonstrated by the finding that antisense repression of an anther-specific isoenzyme provides an efficient method for metabolic engineering of male sterility. The regulation of extracellular invertase by all classes of phytohormones indicates an essential link between the molecular mechanism of phytohormone action and primary metabolism. The up-regulation of extracellular invertase appears to be a common response to various biotic and abiotic stress-related stimuli such as pathogen infection and salt stress, in addition to specific stress-related reactions. Based on the observed co-ordinated regulation of source/sink relations and defence responses by sugars and stress-related stimuli, the identified activation of distinct subsets of MAP kinases provides a mechanism for signal integration and distribution within such complex networks. Sucrose derivatives not synthesized by higher plants, such as turanose, were shown to elicit responses distinctly different from metabolizable sugars and are rather perceived as stress-related stimuli.
AIMS: To assess whether microvascular decompression (MVD) is a safe and efficacious treatment for patients with trigeminal neuralgia (TGN) and multiple sclerosis (MS). METHODS: Case records were reviewed of all patients with TGN and MS who underwent posterior fossa exploration with a view to MVD between 1993 and 2001. In all patients, magnetic resonance tomoangiography (MRTA) demonstrated vascular compression. RESULTS: Nine patients were included in the study. Seven patients underwent MVD alone; in 2 patients a partial sensory rhizotomy of the trigeminal nerve was added to the decompression. All patients had excellent initial pain relief. Recurrence of neuralgia was noted in 5 patients after MVD and in 1 of the 2 patients after partial sensory rhizotomy. Long-term pain relief was obtained in 1 patient who underwent a redo MVD after postoperative MRTA scans demonstrated recurrent vascular compression of the root entry zone (REZ). Thus only 4 out of 9 patients maintained pain relief. In addition, 3 patients experienced transient worsening of their MS. CONCLUSIONS: Although MVD provides good initial pain relief, the recurrence rate is much higher than that obtained in 'idiopathic' TGN. Although all procedures for the treatment of TGN are worse than those for idiopathic TGN, it is concluded that because of the high recurrence rate together with the morbidity associated with the procedure MVD should not be offered to patients with TGN and MS.
Maternal hypothyroidism impairs fetal growth in the rat, but the mechanisms by which this occurs are unknown. Since the fetus derives its glucose supply from the mother, and maternal thyroidectomy may disturb maternal and placental glucose metabolism, we postulated that maternal and/or placental glucose metabolic compromise may contribute to fetal growth retardation in hypothyroid dams. Feto-placental growth, tissue glycogen stores and glucose levels in sera and amniotic fluid were determined in rat dams partially thyroidectomized (TX) before pregnancy and in euthyroid controls. Fetal body weight at 16, 19 and 21 days gestation (d.g.) was related to pre-mating maternal serum total thyroxine (TT(4)) levels; permanent fetal growth retardation occurred in severely (TX(s); pre-mating maternal serum TT(4)<or=16.19 nM) - but not in moderately (TX(m)) - hypothyroid dams. In TX(s) dams, glycogen concentration was elevated in maternal liver and in the fetal side of the placenta at 16 and 19 d.g., and in the maternal side of the placenta at 19 and 21 d.g., despite maternal euglycemia. In contrast, fetal liver glycogen concentration was deficient in TX(m) dams at 19 d.g. and in TX(s) dams at 19 and 21 d.g., and fetal hypoglycemia occurred in TX(s) dams at 21 d.g. Multiple regression analyses indicate that these fetal deficits are strongly associated with the retardation in fetal growth, while the elevated maternal liver and placental glycogen concentrations have no impact on fetal growth near term. The mechanisms by which severe maternal hypothyroidism permanently retards rat fetal growth remain to be determined.
Gold nanoparticles supported on highly hydrophobic ethane bridged Ti incorporated mesoporous organosilica are reported for enhanced vapor phase epoxidation of propene using H2 and O2.
Photodynamic therapy using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) may be applied to the treatment of neoplasms in a variety of organs. In order to enhance existing regimens of photodynamic therapy, we investigated the effects of adding differentiation therapy to photodynamic therapy in human prostate cancer cells in vitro. The objective of differentiation therapy per se is to reverse the lack of differentiation in cancer cells using pharmacological agents. The motivation for this study was to exploit the differentiation-dependent expression of some heme enzymes to enhance tumour cell toxicity of ALA-photodynamic therapy. A short course of differentiation therapy was applied to increase PpIX formation during subsequent ALA exposure. Using the synthetic androgen R1881, isomers of retinoic acid, and analogues of vitamin D for 3 to 4 days, exogenous ALA-dependent PpIX formation in LNCaP cells was increased, along with markers for growth arrest and for differentiation. As a consequence of higher PpIX levels, cytotoxic effects of visible light exposure were also enhanced. Short-term differentiation therapy increased not only the overall PpIX production but also reduced that fraction of cells that contained low PpIX levels as demonstrated by flow cytometry and fluorescence microscopy. This study suggests that it will be feasible to develop protocols combining short-term differentiation therapy with photodynamic therapy for enhanced photosensitisation.
BACKGROUND: Peripheral intravenous (PIV) catheters are widely used in modern medical practice. However, mechanical or infectious complications often necessitate their removal and/or replacement. Heparin has been shown to be effective in prolonging the patency of peripheral arterial catheters and central venous catheters, but may result in life threatening complications, especially in preterm neonates. OBJECTIVES: The primary objective was to determine the effectiveness of heparin versus placebo or no treatment on duration of PIV catheter patency, defined as number of hours of catheter use. The secondary objectives were to assess the effects of heparin on catheter blockage, phlebitis or thrombophlebitis, catheter related sepsis, and complications including abnormality of coagulation profile, allergic reactions to heparin, heparin induced thrombocytopenia, intraventricular/intracranial hemorrhage and mortality. SEARCH STRATEGY: A literature search was performed using the following databases: MEDLINE (1966-December 2001), EMBASE (1980-December 2001), CINAHL (1982-December 2001), Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 2001), and abstracts from the annual meetings of the Society for Pediatric Research, American Pediatric Society and Pediatric Academic Societies published in Pediatric Research (1991-2001). No language restrictions were applied. SELECTION CRITERIA: Randomized or quasi-randomized trials of heparin administered as flush or infusion versus placebo or no treatment were included. Studies which included a neonatal population and reported on at least one of the outcomes were included. DATA COLLECTION AND ANALYSIS: The methodological quality of the studies was assessed using criteria for blinding of randomization, blinding of intervention, completeness of follow-up and blinding of outcome assessment. Data on relevant outcomes were extracted and the effect size was estimated by calculating WMD (weighted mean difference, 95%CI), RR (relative risk, 95% CI) and RD (risk difference, 95% CI). MAIN RESULTS: Eight eligible studies were identified. Heparin was administered either as a flush solution or as an additive to the total parenteral nutrition solution. Five studies reported data on the duration of use of the first catheter. Two of these studies found no statistically significant effect of heparin; two studies showed a statistically significant increase and one study showed a statistically significant decrease in the duration of PIV catheter use in the heparin group. The results were not combined for meta-analysis due to significant heterogeneity of the treatment effect (p<0.01). In addition, there were marked differences between the studies in terms of the methodological quality, the dose, the timing, the route of administration of heparin and the outcomes reported. From a limited number of studies, there were no significant differences between the heparin and the placebo/no treatment groups in the risks of infiltration, phlebitis and intracranial hemorrhage. REVIEWER'S CONCLUSIONS IMPLICATIONS FOR PRACTICE: The effect of heparin on the duration of peripheral intravenous catheter use varied across the studies. Because of clinical heterogeneity and heterogeneity in treatment effect, recommendations for heparin use in neonates with PIV catheters cannot be made. IMPLICATIONS FOR RESEARCH: There are insufficient data concerning the effect of heparin for prolonging PIV catheter use in neonates. Further research on the effectiveness, the optimal dose, and the safety of heparin is required.
OBJECTIVE: Involvement of vertebral column is common in tuberculosis but intramedullary tuberculomas are rare. We report a series of ten cases of intramedullary tuberculomas, which, to the best of our knowledge, is the largest series of biopsy proven intramedullary tuberculomas in English literature. METHODS: During a period of 16 years (1985-2000), ten cases of intramedullary tuberculomas were diagnosed in our department. Of these, eight cases were histologically proven intramedullary tuberculomas. The clinical profile, radiological data and histological slides were reviewed. RESULTS: Age ranged from 18 to 45 years (mean 29.7 years) and there was slight male preponderance (six men, four women). Duration of symptom varied from 3 to 20 months (mean 11.5 months). All of them presented with motor weakness and sensory impairment. Most common site of involvement was dorsal cord followed by cervical, cervicodorsal and dorsolumbar regions. Three patients had associated involvement of lungs, cervical lymphnodes, and brain, and one patient had past history of tuberculous meningitis. Two patients were treated conservatively but surgical excision was done in eight cases followed by medical treatment. CONCLUSION: Radiologically, intramedullary tuberculomas should be differentiated from other space occupying lesions (SOL) to avoid unnecessary surgery especially in those patients with tuberculosis of the other organs. The incidence of intramedullary tuberculomas is likely to increase with a rise in the incidence of AIDS.
PURPOSE: Hippophae rhamnoides L. has been well documented to have anti-oxidative, immunostimulative and regenerative properties and therefore a herbal preparation of H. rhamnoides coded as RH-3 was investigated for its radioprotective action. MATERIALS AND METHODS: RH-3 was administered intraperitonially (i.p.) to mice 30 minutes before whole body irradiation and whole body survival, spleen Colony forming units (CFU) and haematological parameters were studied. To investigate free radical scavenging and antioxidant potential, Fenton reaction, radiation mediated OH radical scavenging and chemically generated superoxide anions scavenging were studied in vitro while inhibition of lipid peroxidation was studied in liver homogenate of mice. RESULTS: A dose of 30 mg/kg body weight of RH-3 rendered 82% survival as compared to no survival in irradiated control. The endogenous CFU counts in mouse spleen on 10th post-irradiation day with and without RH-3 demonstrated radioprotective effect. Various hematological parameters also corroborated the radioprotective effect of RH-3. In a dose dependent manner, RH-3 inhibited Fenton reaction and radiation mediated generation of hydroxyl radicals in vitro, superoxide anion mediated Nitroblue tetrazolium (NBT) reduction and FeSO4 mediated lipid peroxidation in liver. CONCLUSION: Free radical scavenging, acceleration of stem cell proliferation and immunostimulation are the radioprotective attributes, which require further investigations.
Maternal hypothyroidism during pregnancy impairs brain function in human and rat offspring, but little is known regarding the influence of maternal hyperthyroidism on neurodevelopment. We have previously shown that the expression of neuronal and glial differentiation markers in fetal brain is compromised in hypothyroid rat dam pregnancies and have now therefore extended this investigation to hyperthyroid rat dams. Study groups comprised partially thyroidectomised dams, implanted with osmotic pumps infusing either vehicle (TX dams) or a supraphysiological dose of thyroxine (T4) (HYPER dams), and euthyroid dams infused with vehicle (N dams). Cytoskeletal protein abundance was determined in fetal brain at 21 days of gestation by immunoblot analysis. Relative to N dams, circulating total T4 levels were reduced to around one-third in TX dams but were doubled in HYPER dams. Fetal brain weight was increased in HYPER dams, whereas litter size and fetal body weight were reduced in TX dams. Glial fibrillary acidic protein expression was similar in HYPER and TX dams, being reduced in both cases relative to N dams. alpha-Internexin (INX) abundance was reduced in HYPER dams and increased in TX dams, whereas neurofilament 68 (NF68) exhibited increased abundance in HYPER dams. Furthermore, INX was inversely related to - and NF68 directly related to - maternal serum total T4 levels, independently of fetal brain weight. In conclusion, maternal hyperthyroidism compromises the expression of neuronal cytoskeletal proteins in late fetal brain, suggestive of a pattern of accelerated neuronal differentiation.
Gill, liver, kidney, intestine and muscle of some of the common edible fishes captured from Kharkai river were analysed for their iron, zinc, nickel, lead, copper, manganese, chromium and cobalt contents. Kharkai river is one of the principal tributaries of river Subarnarekha and is considered as one of the most polluted rivers in the Chotanagpur plateau. The data generated underline the extent of this pollution and call for immediate redressal.
The expression of c- erbAalpha and -beta encoded thyroid hormone receptors (TR) was investigated in rat placenta between 16 and 21 days of gestation (dg), and in fetal liver and brain at 16 dg, using semi-quantitative RT-PCR and nuclear 3,5,3'-triiodothyronine (T(3)) binding. TRalpha1, TRbeta1, c- erbAalpha 2 and c- erbAalpha 3 mRNA abundance was unchanged in placenta between 16 and 21 dg, as was the dissociation constant (K(d)) of T(3) binding. The maximal T(3) binding capacity (B(max)) in placenta doubled over this period, suggesting placental TR binding activity is post-transcriptionally regulated. Transcript abundance in tissues at 16 dg can be summarized: TRalpha1, placenta=fetal liver fetal brain; c- erbAalpha 2 and alpha3, placenta=fetal liver<fetal brain; TRbeta2; none detected. T(3)binding in fetal liver and brain exhibited equivalent K(d) and B(max), the K(d) being less than 50 per cent of that in placenta, though B(max) was unchanged. The higher K(d)in placenta may reflect tissue-specific patterns of TR modification. In conclusion, rat placenta expresses significant levels of c- erbAalpha and -beta transcripts and protein, providing a possible mechanism of action for T(3) of maternal and fetal origin in this tissue.
A membrane bound form of nitric oxide synthase of human erythrocytes that could be activated by insulin was purified to homogeneity by detergent solubilization of the purified membrane preparation of these cells. The purified enzyme (M(r) 230 KD) was found to be composed of one heavy chain (M(r) 135 KD) and one light chain (Mr 95 KD) held together by disulphide bond(s). Scatchard plot analysis of insulin binding to the purified enzyme showed the presence of 2 different populations of the binding sites and the activation were directly related to the hormone binding to the protein. Line weaver Burk plot of the purified enzyme showed that the stimulation of the enzymic activity by insulin was related to the decrease of K(m) with simultaneous increase of V(max). Treatment of the purified enzyme with anti insulin receptor antibody inhibited the activation of the enzyme and the binding of the hormone to the protein. Furthermore NO itself, at low concentration (<0.4 microM) activated the enzyme, but at higher concentration (>0.8 microM) had no effect on the activation. Incubation of the purified enzyme with insulin simultaneously stimulated the tyrosine kinase and nitric oxide synthase activities of the preparations, that could be inhibited by genistein (an inhibitor of tyrosine kinase). These results indicated that the insulin activated nitric oxide synthase could be the insulin receptor itself.
1-(2,4,5-Trimethoxyphenyl)-1,2-dihydroxypropane (2), a natural phenylpropanoid occurring in Piper clusii, has been synthesized for the first time from toxic beta-asarone (1) of Acorus calamus with osmium tetroxide, while 1 with osmium tetroxide (catalytic amount) in presence of sodium metaperiodate furnished the asaronaldehyde (3) in high yield.
Heat stroke occurs in the desert area of Saudi Arabia quite frequently and manifest in different patterns including coagulopathy. Frequently encountered complications include renal or hepatic failure, rhabdomyolysis, acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), and seizure. Not all of these complications usually occur in the same patient, in case it occurs the mortality reported is significantly high. We describe a case of heat stroke that had nearly all the known complications of heat stroke but recovered from all, except minor neurological deficit in the form of dysarthria and exaggerated deep reflexes.
Non-neoplastic, non-inflammatory cysts of the central nervous system may cause symptoms because of pressure, rupture or secondary inflammation. A total of 145 cases of cysts were reviewed during a study period of 12 years. The clinical details and histological features were noted in all cases. During this period 53 epidermoid cysts, 16 dermoid cysts, 38 colloid cysts, 23 arachnoid cysts, 5 neurenteric cysts, 5 ependymal and glial cysts, 2 Rathke's cleft cysts and 3 unclassified cysts were encountered. The possible histogenesis is also discussed.
We describe three mutations of the red-cell anion exchangerband 3 (AE1, SLC4A1) gene associated with distalrenal tubular acidosis (dRTA) in families from Malaysia and Papua NewGuinea: Gly(701)-->Asp (G701D), Ala(858)-->Asp(A858D) and deletion of Val(850) (DeltaV850). The mutationsA858D and DeltaV850 are novel; all three mutations seem to berestricted to South-East Asian populations. South-East Asianovalocytosis (SAO), resulting from the band 3 deletion of residues400-408, occurred in many of the families but did not itselfresult in dRTA. Compound heterozygotes of each of the dRTA mutationswith SAO all had dRTA, evidence of haemolytic anaemia and abnormal red-cell properties. The A858D mutation showed dominant inheritance and therecessive DeltaV850 and G701D mutations showed a pseudo-dominantphenotype when the transport-inactive SAO allele was also present. Red-cell and Xenopus oocyte expression studies showed that theDeltaV850 and A858D mutant proteins have greatly decreased aniontransport when present as compound heterozygotes (DeltaV850/A858D,DeltaV850/SAO or A858D/SAO). Red cells with A858D/SAO had only 3% ofthe SO(4)(2-) efflux of normal cells, thelowest anion transport activity so far reported for human red cells. The results suggest dRTA might arise by a different mechanism for eachmutation. We confirm that the G701D mutant protein has an absoluterequirement for glycophorin A for movement to the cell surface. Wesuggest that the dominant A858D mutant protein is possibly mis-targetedto an inappropriate plasma membrane domain in the renal tubular cell,and that the recessive DeltaV850 mutation might give dRTA because ofits decreased anion transport activity.