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Biomedical subjects

A K Paul

Publications and source records attributed to A K Paul.

At least 19 recordsLinked to original sources

Synthesis, characterization, cytotoxicity and DNA binding studies of diamminediethyldithiocarbamato-platinum(II) nitrate.

A new complex [Pt(NH3)2(ddtc)]NO3.2H2O as a 1:1 electrolyte has been prepared. This was characterized by spectroscopic methods. The electronic absorption spectrum of this complex in water suggests that it has a square planar geometry. The infrared, 1H NMR and x-ray photoelectron spectroscopic studies suggest the bonding of ammonia molecules and diethyldithiocarbamate as bidentate ligand to platinum(II) in this complex. The 50% inhibition value of this complex against P388 lymphocytic leukemia cells is comparable with cisplatin. This complex interacts with calf thymus DNA by coordinate covalent bond.

Animals

Clinical experiences with vecuronium in children.

The neuromuscular blocking effects of vecuronium have been investigated clinically in children regarding its efficacy and safety. The drug is given either of the two doses--0.08 mg/kg body weight or 0.1 mg/kg body weight in 40 children as a single intravenous bolus injection for endotracheal intubation. Vecuronium in doses of 0.1 mg/kg body weight provided satisfactory clinical relaxation for ideal intubating conditions in all children in reference to the ease of intubation, intermediate duration of action, spontaneous or easy reversal of the neuromuscular block, cardiovascular stability and absence of serious side-effects. Thus vecuronium may be regarded as a useful muscle relaxant in paediatric anaesthesia.

Anesthesia, Intravenous

Platelet-activating factor stimulation of tyrosine kinase and its relationship to phospholipase C in rabbit platelets: studies with genistein and monoclonal antibody to phosphotyrosine.

Platelet-activating factor (PAF) is a proinflammatory lipid that has platelet-stimulating property. PAF receptor-coupled activation of phosphoinositide-specific phospholipase C (PLC) and phosphorylation of several proteins has already been established in our laboratory. To investigate further the molecular mechanism and relationship between activation of PLC and protein phosphorylation, we have used Genistein (a putative inhibitor of tyrosine-specific protein kinases), phosphotyrosine antibody, and phosphoamino acid analysis to probe the involvement of tyrosine kinase in this process. Washed rabbit platelets were loaded with myo-[2-3H]inositol and challenged with PAF (100 nM) after pretreatment with Genistein. PLC-mediated production of radioactive inositol monophosphate, inositol diphosphate, and inositol triphosphate was monitored. PAF alone caused stimulation of PLC activity [( 3H]inositol triphosphate production), whereas pretreatment with Genistein (0.5 mM) diminished PAF-stimulated PLC activity to basal level. Genistein also blocked PAF-stimulated platelet aggregation at this dose. In contrast to Genistein, staurosporine which inhibits protein kinase C, potentiated PAF-stimulated [3H]inositol triphosphate production. Genistein substantially inhibited the combined effects of staurosporine and PAF on inositol triphosphate production. Genistein also reduced PAF-induced phosphorylation of Mr 20,000 and 50,000 proteins. Phorbol 12-myristate 13-acetate-induced Mr 40,000 protein phosphorylation was also affected by Genistein. The above results suggested that Genistein inhibited tyrosine kinase at an early stage of signal transduction by inhibiting PLC. This, in turn, decreased the activation of protein kinase C and, therefore, caused a reduction in Mr 40,000 protein phosphorylation. The inhibition of PLC by Genistein raised the possibility of involvement of tyrosine kinase in PAF receptor-coupled PLC activation. Western blot analysis using monoclonal antibody to phosphotyrosine demonstrated that PAF stimulated the tyrosine phosphorylation of two major proteins of 50,000 and 60,000 molecular weight. When platelets were challenged with PAF after treatment with either Genistein or CV-6209 (a PAF receptor antagonist), the reactivity of these proteins to monoclonal antibody was inhibited. Phosphoamino acid analysis of Mr 50,000 and 60,000 proteins confirmed that PAF increased the phosphorylation of tyrosine residues in both Mr 50,000 and 60,000 proteins and that this was inhibited by Genistein. Thus, PAF caused a receptor-dependent phosphorylation of tyrosine residues on Mr 50,000 and 60,000 proteins. Based on these observations, it is concluded that tyrosine kinase is involved in the PAF receptor-coupled PLC activation and signal transduction mechanism.

Animals

Trimeprazine as oral premedication in children.

The effect of oral trimeprazine alone or in combination with either atropine or glycopyrrolate or pethidine as oral premedication in children was studied. The effects of different drug combinations were evaluated in respect of pre-operative sedation, salivary secretion, induction characteristic, postoperative sedation and postoperative vomiting. The study concludes that trimeprazine in combination with either atropine or glycopyrrolate is mostly effective, safe and satisfactory as oral premedication in children. Trimeprazine along with pethidine can be recommended for all purpose oral medication both in pre- and post-operative period.

Administration, Oral

Effects of metoclopramide and ranitidine on gastric fluid volume and its acidity.

The effects of metoclopramide 10 mg and ranitidine 150 mg on gastric fluid volume and its pH are studied when given orally either alone or in combination, 3 hours before induction of anaesthesia in adult surgical patients. The study shows that metoclopramide causes reduction of gastric fluid volume but does not elevate its pH. Ranitidine elevates the pH of gastric fluid satisfactorily in all cases, but reduces the gastric volume below the critical level only in 50% cases. A combination of the said two drugs offered most satisfactory protection against acid aspiration syndrome almost in all cases. This regime seems to be superior to either ranitidine or metoclopramide alone in order to reduce the risk factors for aspiration of gastric contents.

Adult

Coexistence of guanylate cyclase and atrial natriuretic factor receptor in a 180-kD protein.

Atrial natriuretic factor (ANF) is a peptide hormone that is released from atria and regulates a number of physiological processes, including steroidogenesis in adrenal cortex and testes. The parallel stimulation of membrane guanylate cyclase and corticosterone production in isolated fasciculata cells of rat adrenal cortex has supported the hypothesis of a mediatory role for cyclic guanosine monophosphate (cyclic GMP) in signal transduction. A novel particulate guanylate cyclase tightly coupled with ANF receptor was purified approximately 273,000-fold by two-step affinity chromatography. The enzyme had a molecular size of 180 kilodaltons and was acidic in nature with a pI of 4.7. Its specific activity was 1800 nanomoles of cyclic GMP formed per minute per milligram of protein. The purified enzyme bound ANF with a specific binding activity of 4.01 nanomoles per milligram of protein, a value that is close to the theoretical binding activity of 5.55 nanomoles per milligram of protein for 1 mole of the ligand binding 1 mole of the receptor protein. These results indicate that the guanylate cyclase-coupled ANF receptor exists in a 180-kilodalton protein of rat adrenocortical carcinoma and represent a step toward the elucidation of the basic mechanism of cyclic GMP-mediated transmembrane signal transduction in response to a hormone.

Adrenal Cortex

Heterogeneity of fibroblast response in host-tumor cell-cell interactions in metastatic tumors.

The spread and invasion of tumor cells into host tissues are associated with the release of elevated levels of collagenolytic activity of both host and tumor cell origins. However, the mechanisms of regulation of the enzyme activity is still unresolved. Histological examination of human and animal tumors revealed morphological changes in stromal fibroblasts and mast cells at the tumor periphery. Numerous mast cells appeared at microfoci along the tumor: host tissue junction and mast cell degranulation were associated with collagenolysis. In vitro studies, using rat mammary adenocarcinoma and human lung adenocarcinoma cells, showed that both tumor cells and host fibroblasts participate in matrix degradation. Tumor-associated stromal fibroblasts released higher levels of enzyme activity than normal fibroblasts and were more responsive to stimulation by tumor-conditioned media and soluble mast cell products. Host fibroblasts appear to be heterogeneous populations of responsive and nonresponsive subpopulations based on their response to tumor- or mast-cell-mediated stimulation of collagenase release. Fibroblast subpopulations were obtained by density fractionation of serum-deprived, synchronized confluent fibroblasts on discontinuous Percoll gradient. Density-fractionated fibroblast subpopulations differed in their response to stimulation by mast cell products and tumor-cell-conditioned media. The stimulatory activity of tumor-cell-conditioned media also varied as a function of the metastatic potential of the tumor cells. The data suggest that cellular interactions between tumor cells and select subpopulations of host fibroblasts at the tumor periphery play a key role in host tissue degradation. However, heterogeneity of stromal fibroblasts may determine the site and extent of the tissue damage at foci of tumor invasion.

Animals

Atrial natriuretic factor regulation of cyclic GMP levels and steroidogenesis in isolated fasciculata cells of rat adrenal cortex.

Isolated fasciculata cells of rat adrenal cortex, when incubated with atrial natriuretic factor (ANF), stimulated the levels of cyclic GMP and corticosterone production in a concentration-dependent manner without a rise in the levels of cyclic AMP. The ANF-dependent elevation of cyclic GMP was rapid, with a detectable increment in 30 s. ANF also stimulated the particulate guanylate cyclase. These results not only indicate the coupling of cyclic GMP and corticosterone production with ANF signal, but also demonstrate that, like the ACTH signal, cyclic AMP is not the mediator of ANF-induced adrenocortical steroidogenesis.

Adrenal Cortex

Thyroxine-induced changes of hepatic glucose-6-phosphatase activity and glycogen, protein, RNA and DNA contents in the rat.

Thyroxine (T4) in a dose of 0.1 microgram per g body weight caused in the rat a significant increase in hepatic glucose-6-phosphatase activity, while a reduction of this enzyme activity was observed after 1 microgram of T4 per g. The hepatic glycogen content was found to be depleted and a marked elevation in protein, RNA and DNA contents were observed after both doses of T4.

Animals

Effect of thyroxine on hepatic glucose-6-phosphatase activity and glycogen content of toad (Bufo melanostictus) and Lata fish (Ophicephalus punctatus) at different stages of life.

The effects of thyroxine (T4) on hepatic glucose-6-phosphatase activity and glycogen content in toad (Bufo melanostictus) and Lata fish (Ophicephalus punctatus) were studied in order to show the difference, if any in the enzyme activity and glycogen metabolism in their liver. Thyroxine injections (1 microgram/g) for five consecutive days caused a reduction in hepatic glucose-6-phosphatase activity and glycogen content in toads of immature, juvenile and adult stages. In contrast, Lata fish of different stages showed an enhancement of hepatic glucose-6-phosphatase activity after T4 treatment (1 microgram/g, 5 injections). The liver glycogen content in Lata fish of different age groups was found to be reduced after T4 injections, but not so much as in the toad.

Animals