Severe hyponatremia in a neonate - an unusual association.
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Benzothiadiazines↗
Biomedical subjects
K Srinivasan
Publications and source records attributed to K Srinivasan.
Liquid chromatography--tandem mass spectrometry analysis of cocaine and its metabolites from blood, amniotic fluid, placental and fetal tissues: study of the metabolism and distribution of cocaine in pregnant rats.
The ability to simultaneously quantitate cocaine and its 12 metabolites from pregnant rat blood, amniotic fluid, placental and fetal tissue homogenates aids in elucidating the metabolism and distribution of cocaine. An efficient extraction method was developed to simultaneously recover these 13 components using underivatized silica solid-phase extraction (SPE) cartridges. The overall recoveries for cocaine and its metabolites were studied from pregnant rat blood (47-100%), amniotic fluid (61-100%), placental homogenate (31-83%), and fetal homogenate (39-87%). Extraction of the samples using silica is not classical SPE, but rather allows for the concentration of the sample into a small volume prior to injection and the removal of the proteins due to their strong interaction with the active silica surface. A positive ion mode electrospray ionization liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was used and validated to simultaneously quantitate cocaine and 12 metabolites from these four biological matrices. A gradient elution method with a Zorbax XDB C8 reversed-phase column was used to separate the components. Multiple reaction monitoring (MRM) of a product ion arising from the corresponding precursor ion was used in order to enhance the selectivity and sensitivity of the method. Low background noise was observed from the complex biological matrices due to efficient SPE and the selectivity of the MRM mode. Linear calibration curves were generated from 0.01 to 2.50 ppm. The method also showed high intra-day (n =3) and inter-day (n=9) precision (% RSD) and accuracy (% error) for all components. The limits of detection (LODs) for the method ranged from 0.15 to 10 ppb. The LODs of cocaine and its major metabolites were less than 1 ppb from all four biological matrices. This method was applied to the study of the metabolism and distribution of cocaine in pregnant rats following intravenous infusion to a steady state plasma drug concentration. The following results were observed in the pregnant rat study: (1) the observations correlated strongly with the previous literature data on cocaine metabolism and distribution, (2) cocaine and norcocaine accumulated in the placenta, (3) arylhydroxylation of cocaine was a major metabolic pathway, (4) para-arylhydroxylation of cocaine was favored over meta-arylhydroxylation in rats and (5) accumulation of cocaine and its major metabolites was observed in the amniotic fluid.
Amniotic Fluid↗
Increased QT variability in patients with panic disorder and depression.
This study investigated beat-to-beat QT variability in patients with panic disorder and depression, and normal control subjects using an automated algorithm to compute QT intervals. An increase in QT variability appears to be associated with symptomatic patients with dilated cardiomyopathy and also with an increased risk for sudden death. QT(vm) (QT variability normalized for mean QT interval) and QT(vi) (a log ratio of QT variance normalized for mean QT over heart rate variability normalized for mean heart rate) were significantly higher in patients with panic disorder and depression in supine as well as standing postures (P=0.002 and 0.0001 for QT(vm) and QT(vi), respectively). In another analysis, QT(vi) was significantly higher in patients with panic disorder compared to control subjects in supine as well as standing postures during spontaneous breathing as well as 12, 15 and 20 per minute breathing (P=0.005). These findings are important especially in view of the recent reports of increased risk for cardiovascular mortality and sudden death in patients with anxiety and depression and the utility of QT(vi) as a noninvasive measure of temporal repolarization lability.
Adult↗
Ion chromatographic determination of acidity.
The practice of determining acid concentrations by titrations has remained unchanged for more than a century. We introduce a new approach to the determination of acid concentrations based on cation exchange chromatography. We demonstrate the ability of sulfonated styrene-divinylbenzene based stationary phases to separate the hydrogen ion from other monovalent cations. The eluent is a dilute solution of a neutral salt, sometimes containing a small concentration of the corresponding acid, e.g., sodium ethanesulfonate, pH adjusted with ethanesulfonic acid. The high equivalent conductance (approximately 350 S.cm2/equiv) of H+ and relatively low eluent concentration allows sensitive conductometric detection of H+, down to the 50 microM level under favorable conditions. The conductometric response to H+ can be linear over a wide range of H+ concentrations, from sub-millimolar to several molar concentrations. The system allows the rapid quantitation of strong acids; weak acids can also be determined depending on pKa and injected concentration. The determinations of several strong and weak acids are presented along with factors that govern their chromatographic analysis.
Carboxylic Acids↗
Comparison of cyclodextrin-barbiturate noncovalent complexes using electrospray ionization mass spectrometry and capillary electrophoresis.
Various noncovalent complexes between native and derivatized cyclodextrins (CDs) and barbiturates were studied using capillary electrophoresis (CE) and electrospray ionization mass spectrometry (ESI-MS). This paper involves the study of four aspects of CD-barbiturate noncovalent inclusion complexes. The first study focused on determining the formation of CD-barbiturate inclusion complexes in ESI-MS. This determination was accomplished by the comparison of migration data from CE with ESI-MS inclusion complex peak abundances, which were found to be complementary. The second study found the possibility of predicting native beta-CD mediated CE elution orders for barbiturates using data from ESI-MS. A third study focused on the formation of barbiturate inclusion complexes with derivatized beta-CD and gamma-CD. As part of this study, the effect of the extent of side chain substitution on native CD complexation behavior was investigated. The results indicated that the number of side chains on the CD does not affect the formation of barbiturate complexes with the hydrophobic CD cavity. Finally, a comparison of the hydroxypropyl-beta-CD-barbiturate and hydroxypropyl-gamma-CD-barbiturate complexes in CE and ESI-MS was made to study the relationship between strength of drug-CD binding and enantioresolution. The results from the above studies indicated that the gas phase and the solution state complexes showed comparable behavior indicating that similar interactions played a role in stabilizing these complexes. While it was possible to use the ESI-MS data to determine drug binding to the CDs, it was not possible to predict whether a separation of the enantiomers of a chiral barbiturate would occur. However, the ESI-MS data could be used to eliminate certain CDs from consideration as chiral selectors.
Barbiturates↗
Influence of dietary spices and their active principles on pancreatic digestive enzymes in albino rats.
A few common spices or their active principles were examined for their possible influence on digestive enzymes of pancreas in experimental rat. Groups of animals were maintained for 8 weeks on the following spice diets: curcumin (0.5%), capsaicin (15 mg%), piperine (20 mg%), ginger (50 mg%), cumin (1.25%), fenugreek (2%), mustard (250 mg%) and asafoetida (250 mg%). Dietary curcumin, capsaicin, piperine, ginger, fenugreek and asafoetida prominently enhanced pancreatic lipase activity. Curcumin, capsaicin, piperine, ginger, cumin and asafoetida also stimulated pancreatic amylase. Trypsin was significantly stimulated by curcumin, capsaicin, piperine, ginger and cumin, while chymotrypsin was stimulated by all the spices tested except mustard. This stimulatory influence of test spices on the pancreatic digestive enzymes was however not observed when their intake was restricted to a single oral dose. The positive influences on the pancreatic digestive enzymes exerted by a good number of spices consumed in diet could be a factor contributing to the well recognised digestive stimulant action of spices.
Amylases↗
Complementation of physiological and behavioral defects by a slowpoke Ca(2+) -activated K(+) channel transgene.
The Drosophila slowpoke gene encodes a large conductance calcium-activated potassium channel used in neurons, muscle, and some epithelial cells. Tissue-specific transcriptional promoters and alternative mRNA splicing generate a large array of transcripts. These distinct transcripts are thought to tailor the properties of the channel to the requirements of the cell. Presumably, a single splice variant cannot satisfy the specific needs of all cell types. To test this, we examined whether a single slowpoke splice variant was capable of complementing all slowpoke behavioral phenotypes. Null mutations in slowpoke cause animals to be semiflightless and to manifest an inducible "sticky-feet" phenotype. The well-characterized slowpoke transcriptional control region was used to direct the expression of a single slowpoke splice variant (cDNA H13) in transgenic flies. The endogenous gene in these flies had been inactivated by the slo(4) mutation. Action-potential recordings and voltage-clamp recordings demonstrated the production of functional channels from the transgene. The transgene completely complemented the flight defect, but not the sticky-feet phenotype. We conclude that distinct slowpoke channel isoforms, produced by alternative splicing, are not interchangeable and are required for proper function of different cell types.
Action Potentials↗
Effects of nortriptyline and paroxetine on QT variability in patients with panic disorder.
This study investigated beat-to-beat QT variability in patients with panic disorder before and after treatment with nortriptyline (n = 13) and paroxetine (n = 16), using an automated algorithm to compute QT intervals. An increase in QT variability appears to be associated with symptomatic patients with dilated cardiomyopathy and also with an increased risk for sudden cardiac death. QTvi (QT variability index: a log ratio of QT variance normalized for mean QT over heart rate variability normalized for mean heart rate) was significantly higher in supine posture in patients with panic disorder treated with nortriptyline (P = 0.006) but not paroxetine. Thus paroxetine may be a better drug of choice especially in patients with coexisting cardiac disease. These findings are important especially in view of the recent reports of increased risk for cardiovascular mortality and sudden death in patients with anxiety and depression. QTvi can be a valuable noninvasive measure of temporal repolarization lability, especially to study the side effects of medications which affect cardiac autonomic function.
Adult↗
Renal lesions in streptozotocin-induced diabetic rats maintained on onion and capsaicin containing diets.
Onion (Allium cepa) powder and capsaicin, the pungent principle of red pepper (Capsicum annum) were added in the amounts of 3 g% and 15 mg%, respectively, to the diet of streptozotocin-induced diabetic Wistar rats for 8 weeks. The presence of renal lesions was assessed by the extent and quality of proteinuria and by the leaching of renal tubular enzymes into the urine. Renal integrity was assessed by measuring the activities in the kidney tissue of several key enzymes of carbohydrate metabolism and of polyol pathway, transaminases, and ATPases. Data on enzymuria and proteinuria, activities of kidney ATPases present in diabetic patients, suggested that dietary onion caused significant beneficial modulation of the progression of renal lesions in the diabetic rats. These findings were also corroborated by histologic examination of kidney sections. Dietary capsaicin did not have any favorable influence on renal pathology in diabetes. It is inferred that this beneficial ameliorating influence of dietary onion on diabetic nephropathy may be mediated through onion's ability to lower blood cholesterol levels and to reduce lipid peroxidation.
Journal Article↗
Country profile: India.
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Education, Medical↗
Supercritical fluid extraction and negative ion electrospray liquid chromatography tandem mass spectrometry analysis of phenobarbital, butalbital, pentobarbital and thiopental in human serum.
Four commonly used barbiturates (phenobarbital, butalbital, pentobarbital and thiopental) were analyzed in human serum using supercritical fluid extraction (SFE) and negative ionization LC/ESI-MS/MS. Barbital was used as the internal standard. Carbon dioxide SFE was performed at 40 degrees C and 500 atm, with a total extraction time of 35 min. The analytes were collected off-line in a liquid trap containing absolute methanol. Samples were then concentrated by vacuum centrifugation. The high performance liquid chromatography separation utilized gradient elution with a total analysis time of 21 min. The precursor and major product ions for the four barbiturates were monitored on a triple quadrupole mass spectrometer with negative ion electrospray ionization (ESI) in the multiple reaction monitoring mode as follows: (1) thiopental (m/z 241.20-->58.00), (2) phenobarbital (m/z 231.10-->188.0), (3) pentobarbital (m/z 225.10-->181.90) and (4) butalbital (m/z 222.80-->179.90). In the case of phenobarbital, pentobarbital and butalbital, the most abundant product ion arises from the loss of 43 u (HCNO loss). However, in the case of thiopental, the most abundant product ion was observed at m/z 58.0 (the [M-183]-ion, or NCS-). Mechanisms for the formation of the collision induced dissociation reaction products of these barbiturates are proposed.
Barbiturates↗
Amelioration of renal lesions associated with diabetes by dietary curcumin in streptozotocin diabetic rats.
Curcumin, the coloring principle of the commonly used spice turmeric (Curcuma longa) was fed at 0.5% in the diet to streptozotocin-induced diabetic Wistar rats for 8 weeks. Renal damage was assessed by the amount of proteins excreted in the urine and the extent of leaching of renal tubular enzymes: NAG, LDH, AsAT, AlAT, alkaline and acid phosphatases. The integrity of kidney was assessed by measuring the activities of several key enzymes of the renal tissue: glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, and LDH (Carbohydrate metabolism), aldose reductase and sorbitol dehydrogenase (polyol pathway), transaminases, ATPases and membrane PUFA/SFA ratio (membrane integrity). Data on enzymuria, albuminuria, activity of kidney ATPases and fatty acid composition of renal membranes in diabetic condition suggested that dietary curcumin brought about significant beneficial modulation of the progression of renal lesions in diabetes. These findings were also corroborated by histological examination of kidney sections. It is inferred that this beneficial ameliorating influence of dietary curcumin on diabetic nephropathy is possibly mediated through its ability to lower blood cholesterol levels.
Animals↗
Rapid simultaneous capillary electrophoretic determination of (R)- and (S)-secobarbital from serum and prediction of hydroxypropyl-gamma-cyclodextrin-secobarbital stereoselective interaction using molecular mechanics simulation.
Secobarbital is a hypnotic sedative that is used in the treatment of preoperative anxiety and to manage elevated intracranial pressures and cerebral ischemia due to neurosurgical procedures. Stereoselective resolution is first predicted using hydroxypropyl-gamma-cyclodextrin (HPGCD)-(R)- and (S)-secobarbital transient complex energy calculations using SYBYL 6.01 molecular modeling software. Separation is accomplished as predicted using 40 mM HPGCD in 50 mM phosphate buffer (pH 9.0), resulting in a rapid, sensitive method for the determination of (S)- and (R)-enantiomers of secobarbital from serum using solid-phase extraction, capillary electrophoresis (CE), and ultraviolet detection. The method involves extraction of both enantiomers and the internal standard, aprobarbital, from serum using C18 Bond-Elut solid-phase cartridges. The CE system consists of fused-silica capillary (52 cm x 75-microns i.d.) maintained at a run voltage of 15 kV with detection performed at a wavelength of 254 nm. The detection and quantitation limits from serum for (S)- and (R)-secobarbital are 1 microgram/mL. Linear calibration curves from 1 to 60 micrograms of both (S)- and (R)-secobarbital show a coefficient of determination of more than 0.999. The precision and accuracy of the method, calculated as relative standard deviation (%) and percent error, are 0.35-4.48% and 0.71-8.67%, respectively, for (R)-secobarbital and 0.39-4.08% and 2.16-3.70%, respectively, for (S)-secobarbital.
Circadian Rhythm↗
Capillary electrophoresis stereoselective determination of R-(+)- and S-(-)-pentobarbital from serum using hydroxypropyl-gamma-cyclodextrin, solid-phase extraction and ultraviolet detection.
Pentobarbital is a sedative hypnotic which is used in the treatment of people suffering from anxiety related conditions and to manage elevated intracranial pressures and cerebral ischemia due to neurosurgical procedures. This paper develops and validates a rapid and sensitive method for the determination of S-(-)- and R-(+)-enantiomers in serum using capillary electrophoresis (CE) and UV detection. Stereoselective resolution was accomplished using 40 mM hydroxypropyl-gamma-cyclodextrin contained in 50 mM phosphate buffer pH 9.0. The method involves a solid-phase extraction of both the enantiomers and the internal standard, aprobarbital, from serum using C18 Bond-Elut cartridges. The CE system consists of a 52 cmX75 microm I.D. fused-silica capillary maintained at a run voltage of 15 kV with sample detection performed at 254 nm. The detection and quantitation limits for S-(-)- and R-(+)-pentobarbital are 1 microg/ml from serum. Linear calibration curves from 1 to 60 microg of both S-(-)- and R-(+)-enantiomers show a coefficient of determination of more than 0.999. The precision and accuracy of the method calculated as R.S.D. and error are 0.20-2.20% and 0.00-4.40%, respectively for R-(+)-pentobarbital and 0.30-2.19% and 0.30-6.40%, respectively for S-(-)-pentobarbital.
Barbiturates↗
Plant foods in the management of diabetes mellitus: vegetables as potential hypoglycaemic agents.
Vegetables are among the numerous plant adjuncts tried for the treatment of diabetes mellitus. A few vegetables that are commonly consumed in India have been claimed to possess antidiabetic potency. In recent years, there has been a renewed interest to screen such plant food materials, for a possible beneficial use. Considerable amount of work has been carried out in this regard with bitter gourd (Momordica charantia) and ivy gourd (Coccinia indica) both in experimental animals and human diabetic subjects. Majority of these studies have documented the beneficial effect of the fruit of bitter gourd and leaf of ivy gourd when administered orally as a single dose. The hypoglycaemic influence is claimed to be mediated through an insulin secretagogue effect or through an influence on enzymes involved in glucose metabolism. The limited number of studies on other vegetables such as cabbage (Brassica oleracia), green leafy vegetables, beans and tubers have shown the beneficial hypoglycaemic influence in both experimental animals and humans. There is scope for more extensive research in this area, especially to examine the long term beneficial effect of dietary vegetables, to identify the active principle, and to understand the mechanism of action, which is at present unclear. Since diet forms the mainstay in the management of diabetes mellitus, there is scope for exploiting the antidiabetic potency of vegetables to the maximum extent. Such plant food adjuncts possessing hypoglycaemic activity appear to hold promise as potential antidiabetic agents.
Animals↗
Hypolipidemic action of curcumin, the active principle of turmeric (Curcuma longa) in streptozotocin induced diabetic rats.
Streptozotocin-induced diabetic rats were maintained on 0.5% curcumin containing diet for 8 weeks. Blood cholesterol was lowered significantly by dietary curcumin in these diabetic animals. Cholesterol decrease was exclusively from LDL-VLDL fraction. Significant decrease in blood triglyceride and phospholipids was also brought about by dietary curcumin in diabetic rats. In a parallel study, wherein diabetic animals were maintained on a high cholesterol diet, the extents of hypercholesterolemia and phospholipidemia were still higher compared to those maintained on control diet. Curcumin exhibited lowering of cholesterol and phospholipid in these animals also. Liver cholesterol, triglyceride and phospholipid contents were elevated under diabetic conditions. Dietary curcumin showed a distinct tendency to counter these changes in lipid fractions of liver. This effect of curcumin was also seen in diabetic animals maintained on high cholesterol diet. Dietary curcumin also showed significant countering of renal cholesterol and triglycerides elevated in diabetic rats. In order to understand the mechanism of hypocholesterolemic action of dietary curcumin, activities of hepatic cholesterol-7a-hydroxylase and HMG CoA reductase were measured. Hepatic cholesterol-7a-hydroxylase activity was markedly higher in curcumin fed diabetic animals suggesting a higher rate of cholesterol catabolism.
Animals↗
Influence of dietary capsaicin and onion on the metabolic abnormalities associated with streptozotocin induced diabetes mellitus.
Effect of feeding 15 mg% capsaicin diet or 3% freeze dried onion powder containing diet were examined in albino rats rendered diabetic with streptozotocin injection. Diabetic rats maintained on onion diet for 8 weeks excreted comparatively less amounts of albumin, urea, creatinine and inorganic phosphorus. Dietary onion also partially reversed the abnormalities in plasma albumin, urea, creatinine and inorganic phosphorus in diabetic animals. Onion also produced a significant reduction in hyperglycemic status of diabetic animals. Diabetic rats maintained on onion diet had a lowered relative liver weight at the end of the study compared to diabetic control group. Diabetic rats fed onion diet also exhibited lowered lipid peroxides in circulation and in urine when compared to diabetic control group. Blood cholesterol was lowered significantly by dietary onion in diabetic animals. Cholesterol decrease was exclusively from LDL-VLDL fraction. Significant decrease in blood phospholipids and triglycerides also brought about by dietary onion. Hepatic cholesterol, triglycerides, phospholipids which were elevated under diabetic condition were countered significantly by dietary onion. Dietary capsaicin did not have any significant influence on any of the parameters tested in diabetic rats. Thus, the study reveals that onion feeding improves the metabolic status in diabetic condition, probably because of its hypoglycemic as well as hypocholesterolemic effect.
Animals↗
Birth-based approach to family planning: an empirical justification.
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Asia↗