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Biomedical subjects

A K Dutta

Publications and source records attributed to A K Dutta.

At least 19 recordsLinked to original sources
PubMed1992

Lipophilic amino alcohols with calcium channel blocking activity.

A series of novel lipophilic amino alcohols, analogs of the anticholinergic drug vesamicol, were evaluated for Ca2+ channel blocking activity. The effects of these drugs on depolarization-induced intracellular free Ca2+ concentration ([Ca2+]i) transients were examined in single NG108-15 cells and dorsal root ganglion (DRG) neurons in culture. [Ca2+] was recorded with the Ca2+ indicator Indo-1 and a dual emission microfluorimeter. Structure-activity studies indicated that features required for Ca2+ channel blocking activity were distinct from those required for anticholinergic activity. In particular, the Ca2+ channel blocking activity was insensitive to the configuration at the chiral center, whereas the anticholinergic activity was clearly enantioselective. One of the most active compounds, 3-(3-bromophenyl)-2-hydroxy-1-[1-(4-phenylpiperidinyl)]propane (2b), was characterized in more detail. This compound inhibited the dihydropyridine-sensitive Ca2+ channel response in NG108-15 cells, evoked by depolarization with 50 mM K+, with an IC50 of 5 microM. Field potential stimulation of DRG neurons elicited [Ca2+]i transients mediated by at least three Ca2+ channel subtypes; compound 2b inhibited the entire Ca2+ channel response with an IC50 of 1 microM. A key element required for Ca2+ channel blocking activity was the presence of an electron withdrawing substituent on the pendant phenyl ring. Modification of the amino alcohol structure may lead to more potent compounds with broad spectrum Ca2+ channel blocking activity. These structures provide a new chemical starting point for the development of Ca2+ antagonists.

Amino Alcohols↗
PubMed1992

Radioiodinated 2-hydroxy-3-(4-iodophenyl)-1-(4-phenylpiperidinyl)propane: potential radiotracer for mapping central cholinergic innervation in vitro.

Radioiodinated 2-hydroxy-3-(4-iodophenyl)-1-(4-phenylpiperidinyl)propane, 5 (4-HIPP), was synthesized and evaluated as a simple vesamicol-like radiotracer for mapping cholinergic pathways in the brain. Both enantiomers of 5 exhibit significant accumulation (approx. 2% of injected dose) and prolonged retention (t1/2 greater than 3 h) within the rat brain. The accumulation of radioiodinated 5 in the rat brain was reduced by up to 70% in the presence of vesamicol and its analogs. The levorotary isomer (-)-4-[123I]HIPP exhibits significant accumulation in the monkey brain, with a half-life of about 9 h. Radioiodinated 5 may therefore be a useful tool for studying cholinergic pathways in the brain.

Animals↗
PubMed1992

Enhancement by nickel(II) and L-histidine of 2'-deoxyguanosine oxidation with hydrogen peroxide.

Conversion of the 2'-deoxyguanosine (dG) residues in calf thymus DNA to 8-hydroxy-2'-deoxyguanosine (8-OH-dG) was achieved at physiological pH by treating the DNA with hydrogen peroxide (H2O2) in the presence of nickel(II) chloride (NiCl2). The effectiveness of this reaction was enhanced by L-histidine (His) which forms the Ni(II)-His2 complex. Similar effects of NiCl2 and His were observed on hydroxylation of pure dG with H2O2. The rate of pure dG conversion to 8-OH-dG at 37 degrees C (100 mM phosphate buffer) depended on combination and concentration of the reagents and on pH. Following 24 h incubation at pH 7.4 of 0.75 mM dG with 30 mM H2O2 and 1 mM NiCl2, dG was converted into 8-OH-dG to the extent of 0.05% in the absence of His and 0.45% in the presence of 2 mM His. After 24 h incubation at pH 7.4 of 0.5 mg/ml DNA with 7.5 mM H2O2 and 0.1 mM NiCl2, 0.18% of the dG moiety was converted into 8-OH-dG in the absence of His and 0.42% in the presence of 0.2 mM His. Interestingly, a mixture of H2O2 with His was also capable of oxidizing dG to 8-OH-dG even in the absence of NiCl2, albeit less effectively than in the presence of NiCl2. This effect was not suppressed after treatment of dG, His and the buffer with Chelex to remove divalent metal contaminants, if any. The exact chemistry of the observed phenomena remains to be determined. Since the Ni(II)-His2 complex is the major low mol. wt nickel carrier in mammalian organisms, the observed redox properties of this complex, reported here for the first time, may be crucial for the toxicity and carcinogenicity of nickel.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1992

Immunogenicity of enhanced potency inactivated polio vaccine.

Fifty two children were immunized with two doses of enhanced potency inactivated polio vaccine in order to determine its efficacy. The vaccine was very efficacious with 92.3, 92.3 and 88.3% of the children seroconverting to the three poliovirus types, respectively. The vaccine was equally efficacious whether the two doses were given at 4-week or 8-week intervals or when immunization was started at 6-7 weeks of age or later. The presence of maternal antibodies did not interfere significantly with the seroresponse to two doses of IPV-E. The study recommends that two doses of IPV-E give satisfactory seroconversion rates. Immunization can be started as early as 6 weeks age and the two doses can be given at 4 weeks interval to complete primary immunization against poliomyelitis.

Antibodies, Viral↗
PubMed1992

Reliability of capillary blood gas estimation in neonates.

In order to compare the reliability of capillary blood gases to the arterial blood gases, we studied fifty one neonates with moderate birth asphyxia. A significant difference (p less than 0.05) was found between the capillary and the arterial blood gas values with respect to blood pH, PCO2 PO2 and oxygen saturation. However, the levels of blood bicarbonate as assessed by the 2 samples were comparable. Capillary blood gas values are unsatisfactory indicators of the arterial blood gas values and may result in inappropriate management.

Asphyxia Neonatorum↗
PubMed1991

Acyclic analogues of 2-(4-phenylpiperidino)cyclohexanol (vesamicol): conformationally mobile inhibitors of vesicular acetylcholine transport.

Several 1,3-disubstituted propan-2-ols and one alpha,beta-disubstituted ethanol (11i) were synthesized and evaluated as potential acyclic mimics of the vesicular acetylcholine transport inhibitor 2-(4-phenylpiperidinyl)cyclohexanol (1, vesamicol, AH5183). Analogues containing the 4-phenylpiperidyl fragment (11a, 11b) were more potent than those containing the 4-phenylpiperazyl moiety (11e, 11f). Substitution at the second terminal carbon of the propyl (or ethyl) fragment with simple lipophilic aryl substituents yielded potent inhibitors of vesicular acetylcholine storage, including (-)-11a and d-11i, which are equipotent with vesamicol. However, the activity of analogues containing bicyclic aryl groups was susceptible to aryl substitution patterns (11g vs 11h), indicating a definite receptor site topography. In addition, the inhibitory activity of these acyclic analogues was enantioselective, exhibiting a preference, similar to the parent vesamicol, for the levorotatory isomer [(-)-11a vs (+)-11a]. Therefore, the simple lipophilic acyclic vicinal amino alcohols may successfully mimic the biological activity of vesamicol.

Acetylcholine↗
PubMed1991

Neonatal mortality patterns in an urban hospital.

Neonatal mortality rate is perhaps the most reliable indicator of the perinatal outcome. An assessment of perinatal outcome can be made through knowledge of causes of death. This study was carried out to evaluate the neonatal deaths in our hospital. Live births (n = 7309) and deaths (n = 328) during a 6 months period were retrospectively analyzed. These were grouped into non-preventable and potentially preventable causes of death. The single most important factor contributing to the mortality was respiratory distress (29.3%) followed by sepsis (24.4%) and birth asphyxia (16.2%). The non-preventable causes of mortality (e.g., lethal congenital malformations, extremely low birth weight) accounted for 10.4% of the total mortality. The idealized neonatal mortality rate was 4.6/1000 live births, while the salvageable death rate was 40.2/1000 live births. The mortality increased significantly if the birth weight fell below 2 kg. The salvageable deaths could perhaps be prevented through better antenatal and intranatal care, ventilatory support and prevention of sepsis.

Cause of Death↗
PubMed1991

Stress associated gastric bleeding in newborn--role of ranitidine.

Stress associated gastric bleeding in sick neonates is an ominous sign and frequently heralds mortality. This study was aimed at evaluating the H2 receptor antagonist drug-ranitidine in the treatment of this bleeding. Thirty eight neonates with gastric hemorrhage were included in the study. Twenty neonates were given ranitidine while 18 acted as controls. Both groups were well matched with respect to various parameters. Gastric bleeding was controlled earlier in the ranitidine group in contrast to the control group. No untoward side effects were observed with the use of ranitidine. The use of this drug in stress associated gastric bleeding in neonates is recommended.

Humans↗
PubMed1991

Acute renal failure in asphyxiated newborns.

The study was undertaken to evaluate the occurrence of renal failure following perinatal asphyxia in the newborns. Thirty newborns with severe birth asphyxia were included in the study along with 30 normal newborns who comprised the control group. Any neonate presenting with oliguria or blood urea more than 40 mg/dl or creatinine more than 1 mg/dl was subjected to a fluid and diuretic challenge. If oliguria or renal dysfunction persisted then the child was labelled as renal failure and these subjects were further investigated. It was observed that 43% of asphyxiated babies developed acute renal failure (ARF); 69.2% babies had oliguric renal failure. While no significant correlation could be seen between Apgar scores at 5 and 10 min and development of ARF, a significant relationship was seen between hypoxic-ischemic encephalopathy and ARF. Patients with oliguric ARF carried a poorer prognosis as compared to non-oliguric ARF.

Acute Kidney Injury↗
PubMed1991

Renal dysfunction in septicemic newborns.

The study was undertaken to assess the association and incidence of acute renal failure (ARF) in septicemic neonates. Thirty neonates with septicemia formed the subject matter. Neonates with renal dysfunction were labelled as ARF patients after non responsiveness to a fluid and a diuretic challenge. Renal function tests were also evaluated. Nearly 15% neonates with septicemia developed ARF which was predominantly oliguric in type. The mortality rate in the septicemic neonates with ARF was significantly high. Further the mortality in neonates with oliguric ARF was significantly higher than those with non-oliguric ARF.

Acute Kidney Injury↗
PubMed1991

Maternal participation in the care of the high risk infant: follow-up evaluation.

Fifty mothers of high risk infants admitted to the Neonatal Special Care Unit were followed up to the postnatal age of 2.5 mo +/- 15 days. Twenty five mothers (Group I) had stayed in the nursery with the infant for a period of 4.8 +/- 4.6 days until the discharge of the infant, providing expressed milk and participating in the non-specialised care of the infant. The other 25 mothers (Group II) remained separate from their babies for the duration of the latter's stay in the hospital although some of the mothers did come off and on to give expressed human milk and at times handle their infants. Family features such as parental age, educational and occupational status, and presence of residential elder women, were similar in the two groups. Infant characteristics too, such as sex, birth weight, and early neonatal morbidity were also comparable. Operative deliveries and maternal problems were as expected more in the separated group. The duration of the infants' hospital stay was also more in the latter (9.5 +/- 3.5 vs 6.3 +/- 3.9 days; p greater than 0.05). Subsequent to their discharge, mothers who had stayed with the infant identified the following benefits of their stay--acquiring of knowledge relevant to infant care especially hygiene (19) and their personal involvement in the care of their infant (12), both of which they said increased their self confidence in looking after the babies after discharge, and provision of breast milk round the clock (17).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Flexible N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogues: synthesis and monoamine oxidase catalyzed bioactivation.

Eighteen analogues of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were synthesized and evaluated as substrates of monoamine oxidase. In general, the flexible analogues, characterized by the presence of a methylene (or ethylene) bridge between the aryl/heteroaryl and tetrahydropyridyl moieties, were better substrates of the enzyme than the conformationally restricted MPTP. It is suggested that the increased oxidative activity of these flexible analogues reflects enhanced binding due to the ability of the C-4-aryl/heteroaryl substituent to gain access to a hydrophobic pocket within the substrate binding site.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1990

Liver dysfunction in severe birth asphyxia.

A total of 46 full term, appropriate for gestational age neonates were included in this study. Out of this, 31 infants had suffered severe birth asphyxia, while 15 normal babies formed the control group. The liver function tests of the asphyxiated group was deranged in 64.52% babies. There was 60% mortality in asphyxiated babies with deranged liver function. The serum levels of transaminases (SGOT, SGPT) and alkaline phosphatase in non-survivors were significantly higher than those of survivors.

Asphyxia Neonatorum↗
PubMed1990

Delayed cesarean section: neonatal outcome.

One hundred and twenty one consecutive cesarean sections producing single term, appropriate for gestational age neonates, out of which 85% were emergency cesareans, were included in this study. Fetal distress, nonprogress of labour, and cephalopelvic disproportion were major indications for surgery. The waiting period varied from less than 30 minutes to greater than 4 hours. More than 50% of neonates studied suffered from some problem. The morbidity increased significantly if cesarean section was delayed for more than two hours.

Cesarean Section↗
PubMed1990

Role of cimetidine in prevention and treatment of stress induced gastric bleeding in neonates.

Gastric bleeding from stress ulcers in acutely sick infants frequently signals impending mortality. This study was carried out to evaluate the efficacy of cimetidine in preventing and treating stress ulcers in such neonates. One hundred babies were included in this study. Out of this, 32 babies were given prophylactic cimetidine and 68 neonates acted as controls. It was observed that the babies on prophylactic cimetidine fared better than controls. In the second part of study, 77 neonates with clinical evidence of hemorrhage were included, 43 were put on cimetidine and 34 acted as controls. It was observed that babies on cimetidine therapy showed a better response. The gastric bleeding stopped earlier, and more babies responded favourably to this therapy. Use of cimetidine in stress induced bleeding in high risk neonates is recommended.

Cimetidine↗