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Biomedical subjects

S Datta

Publications and source records attributed to S Datta.

At least 127 records · Page 7Linked to original sources

Hepatoprotective effect of a protein isolated from Cajanus indicus (Spreng) on carbon tetrachloride induced hepatotoxicity in mice.

Treatment with hepatotoxin namely carbon tetrachloride (CCl4) (0.1 ml/100 g of body weight; twice a week) induced acute hepatic necrosis in Swiss albino mice (male; body weight 30 g +/- 2), with significant alteration in the activities of glutamic oxaloacetic transaminase (GOT); glutamic pyruvic transaminase (GPT); alkaline phosphatase (AP) and serum bilirubin. Administration of a protein fraction isolated from the leaves of C. indicus counteracted the action of CCl4 on transaminase, phosphatase showing hepatoprotection. Daily treatment with a purified protein fraction 'X' from the above plant (0.5 mouse ml i.p; 50-60 micrograms/ml) for a period of 7, 14, 21 days respectively showed decreased activities of serum transaminases alkaline phosphatase and decreased levels of serum bilirubin. These findings were further confirmed by histopathological study of liver.

Animals↗

Visual evoked response in different types of amblyopia before and after occlusion therapy.

Visual evoked response (VER) was analysed in control eyes and in different types of amblyopias. A general trend of a non-linear decrease in latency with an improvement of visual acuity has been noted. Individual correlation co-efficients between visual acuity and VER parameters in different types of amblyopias as compared to whole population showed no significant changes. The correlation co-efficient between post-treatment visual acuity and latency reflects a general trend of a non-linear decrease in latency with an improvement of visual acuity.

Amblyopia↗

Endogenous and exogenous nitric oxide in the pedunculopontine tegmentum induces sleep.

Mesopontine cholinergic cells in the pedunculopontine tegmental (PPT) nuclei modulate the control of the wake-sleep cycle by releasing acetylcholine to their target structures. These cells also synthesize nitric oxide (NO) which diffuses into the extracellular space and acts as a neuronal messenger. The present study is based on the hypothesis that NO synthesis and its presence in the extracellular space in the PPT play a functional role in regulating the behavioral states of waking and sleep. This hypothesis was tested by microinjecting a control vehicle, NO donor, S-Nitroso-N-acetylpenicillamine (SNAP) and a competitive inhibitor of NO synthase enzyme (NOS), N(G)-Nitro-L-arginine methylester hydrochloride (L-NAME) into the PPT while quantifying the effects on wakefulness and sleep. Six cats were implanted with bilateral guide tubes for PPT microinjection and with standard electrodes to measure waking, slow-wave sleep (SWS), and rapid eye movement (REM) sleep. Five-hour free-moving polygraphic recordings were made following each microinjection (0.25 microl) of control saline, SNAP or L-NAME. Following microinjection of SNAP into the cholinergic cell compartments of the PPT, SWS and REM sleep were increased by 41.65% and 72.10% respectively, compared to the control microinjection. Microinjection of L-NAME reduced SWS and REM sleep by 40.33% and 62.05%, respectively, compared to controls. The present results demonstrate that endogenous NO synthesized within the PPT cholinergic cells functions as a paracrine signal in the control of waking and sleep by modulating local cholinergic cells.

Animals↗

Superiority of multi-orifice over single-orifice epidural catheters for labor analgesia and cesarean delivery.

STUDY OBJECTIVE: To investigate whether a change from a single-orifice to multi-orifice catheter could reduce the incidence of inadequate epidural blocks requiring replacement of the epidural catheter in obstetric patients. STUDY DESIGN: Prospective before-after cohort study. SETTING: Obstetric unit at a university hospital. PATIENTS: 872 patients requesting epidural analgesia for vaginal delivery or cesarean section. INTERVENTIONS: Patients received epidural analgesia via single-orifice (n = 433) or multi-orifice (n = 439) epidural catheters, depending on the month of the trial. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, obstetric procedure, anesthesiologist characteristics, and details of epidural placement did not differ significantly between the groups. The overall replacement rate was 14.3% in the single-orifice group versus 9.3% in the multi-orifice group (p = 0.032). There were no difference in the frequency of replacement for subarachnoid placement or migration, immediate intravascular placement, vascular migration, or absence of any block. Significantly fewer catheters were replaced in the multi-orifice group for inadequate analgesia, defined as unblocked segments or unilateral block (6.4% vs. 2.8%, p = 0.018). Paresthesias were less common in the multi-orifice group (22.4% vs. 31.5%, p = 0.003). There were no unrecognized subarachnoid or vascular catheter placements in either group. CONCLUSIONS: The multi-orifice design offers significant advantages over the single-orifice type for obstetricepidural analgesia.

Adult↗

Cellular basis of pontine ponto-geniculo-occipital wave generation and modulation.

1. Pontogeniculooccipital (PGO) waves are recorded during rapid eye movement (REM) sleep from the pontine reticular formation. 2. PGO wave-like field potentials can also be recorded in many other parts of the brain in addition to the pontine reticular formation, but their distribution is different in different species. Species differences are due to variation in species-specific postsynaptic target sites of the pontine PGO generator. 3. The triggering neurons of the pontine PGO wave generator are located within the caudolateral peribrachial and the locus subceruleus areas. 4. The transferring neurons of the pontine PGO generator are located within the cholinergic neurons of the laterodorsal tegmentum and the pedunculopontine tegmentum. 5. The triggering and transferring neurons of the pontine PGO wave generator are modulated by aminergic, cholinergic, nitroxergic, GABA-ergic, and glycinergic cells of the brainstem. The PGO system is also modulated by suprachiasmatic, amygdaloid, vestibular, and brainstem auditory cell groups.

Eye Movements↗

Involvement of a 70-kb plasmid of the epidemic Shigella dysenteriae type 1 (Dt66) strain in drug-resistance, lipopolysaccharide synthesis, and virulence.

The present work characterizes a 70 kb plasmid of the Indian epidemic isolate Shigella dysenteriae type 1 strain Dt66 in relation to virulence and drug-resistance characters. Curing of the plasmids of Dt66 strain by acriflavine (AF) yielded seven groups of AF-cured derivatives. One group of derivatives containing 5 plasmids (70-2.5 kb) as against 6 (120-2.5 kb) in the wild type showed resistance to chloramphenicol, pivmecillinam, streptomycin, and tetracycline (CmrPivrSmrTcr) but sensitivity for ampicillin and nalidixic acid (AmsNals). This derivative when used as donor in conjugation experiments with a plasmidless E. coli KL318 strain (AmsCmsPivsSmrTcsNalr) as recipient, transferred only its 70 kb plasmid into the recipient with concomitant transfer of the CmrPivr phenotype. Both the donor and the transconjugant exhibited a diffuse pattern of adherence and produced keratoconjunctivitis in guinea pigs. Transconjugants contained a 42 kDa lipopolysaccharide band which was absent in recipient. Moreover, both donor and transconjugants showed Congo red binding ability. The results suggest that the 70 kb plasmid of S. dysenteriae Dt66 strain encodes not only Cmr,Pivr character but also is associated with virulence-related characters such as Congo red binding, LPS-biosynthesis, HeLa cell adherence, and keratoconjunctivitis related to virulence.

Animals↗

Estrogen-induced changes in protein binding of bupivacaine during in vitro fertilization.

BACKGROUND: Patients having in vitro fertilization (IVF) procedures that use gonadotropin-releasing hormone agonist down-regulation undergo hormonal manipulation of estrogen concentrations to induce oocyte maturation. After achieving minimal estrogen concentrations (baseline), stimulation increases estrogen concentrations to supraphysiologic levels, leading to egg retrieval. The isolated effect of estrogen on protein binding has not previously been reported. This study was conducted to measure the effect of estrogen concentrations on protein binding of two concentrations of bupivacaine, 1 microg/ml and 5 microg/ml, corresponding, respectively, to systemic concentrations expected after administration of epidural anesthesia and associated with bupivacaine toxicity. Serum proteins were measured to address the mechanism. METHODS: Twenty-nine healthy women undergoing IVF procedures were enrolled and venous samples were drawn at times of minimal and maximal estrogen concentrations. The percentage of free bupivacaine was determined at fixed concentrations of 1 and 5 microg/ml. Serum albumin and alpha1-acid glycoprotein concentrations were measured at baseline and at retrieval in a group of 24 women. RESULTS: The percentage of free bupivacaine increased between times of minimal and maximal serum estrogen concentrations, corresponding to decreased protein binding. Concentrations of serum albumin and alpha1-acid glycoprotein decreased between baseline and retrieval times. CONCLUSIONS: Patients undergoing IVF procedures demonstrate a decrease in protein binding of bupivacaine from baseline concentrations. These changes may be explained by a decrease in albumin and alpha1-acid glycoprotein. During anesthesia for egg retrieval, clinicians should consider the implications of increased free fraction of drug, especially for highly protein-bound agents.

Anesthetics, Local↗

Hydrogen bonding in peptide helices. Analysis of two independent helices in the crystal structure of a peptide Boc-Val-Ala-Leu-Aib-Val-Ala-Phe-OMe.

The crystal structure determination of the heptapeptide Boc-Val-Ala-Leu-Aib-Val-Ala-Phe-OMe reveals two peptide helices in the asymmetric unit. Crystal parameters are: space group P2(1), a = 10.356(2) A, b = 19.488(5) A, c = 23.756(6) A, beta = 102.25(2) degrees, V = 4685.4 A3, Z = 4 and R = 5.7% for 7615 reflections [I > 3 sigma (I)]. Both molecules adopt largely alpha-helical conformations with variations at the C-terminus. Helix type is determined by analysing both 4-->1 and 5-->1 hydrogen-bond interactions and comparison with the results of analysis of protein structures. The presence of two 4-->1 hydrogen-bond interactions, besides four 5-->1 interactions in both the conformations provides an opportunity to characterize bifurcated hydrogen bonds at high resolution. Comparison of the two helical conformations with related peptide structures suggests that distortions at the C-terminus are more facile than at the N-terminus.

Amino Acid Sequence↗

Excitation of the brain stem pedunculopontine tegmentum cholinergic cells induces wakefulness and REM sleep.

Considerable evidence suggests that brain stem pedunculopontine tegmentum (PPT) cholinergic cells are critically involved in the normal regulation of wakefulness and rapid eye movement (REM) sleep. However, much of this evidence comes from indirect studies. Thus, although involvement of PPT cholinergic neurons has been suggested by numerous investigations, the excitation of PPT cholinergic neurons causal to the behavioral state of wakefulness and REM sleep has never been directly demonstrated. In the present study we examined the effects of three different levels of activation of PPT cholinergic cells in wakefulness and sleep behavior. The effects of glutamate on the activity of PPT cholinergic cells were studied by microinjection of one of the three different doses of L-glutamate (0.3, 1.0, and 3.0 microg) or saline (vehicle control) into the PPT cholinergic cell compartment while quantifying the effects on wakefulness and sleep in free moving chronically instrumented cats. All microinjections were made during wakefulness and were followed by 4 h of recording. Polygraphic records were scored for wakefulness, slow-wave sleep states 1 and 2, slow-wave sleep with pontogeniculooccipital waves, and REM sleep. Dependent variables quantified after each microinjection included the percentage of recording time spent in each state, the latency to onset of REM sleep, the number of episodes per hour for REM sleep, and the duration of each REM sleep episode. A total of 48 microinjections was made into 12 PPT sites in six cats. Microinjection of 0.3- and 1.0-microg doses of L-glutamate into the cholinergic cell compartment of the PPT increased the total amount of REM sleep in a dose-dependent manner. Both doses of L-glutamate increased REM sleep at the expense of slow-wave sleep but not wakefulness. Microinjection of 3.0 microg L-glutamate kept animals awake for 2-3 h by eliminating slow-wave and REM sleep. The results show that the microinjection of the excitatory amino acid L-glutamate into the PPT cholinergic cell compartments can increase wakefulness and/or REM sleep depending on the L-glutamate dosage. These findings unambiguously confirm the hypothesis that the excitation of the PPT cholinergic cells is causal to the generation of wakefulness and REM sleep.

Animals↗

Sucralfate impedes intestinal epithelial sheet migration in a Caco-2 cell culture model.

Sucralfate, which binds to the matrix of the ulcer bed, is theoretically advantageous for duodenal ulcer therapy, but has not fulfilled its promise clinically. We examined the effects of sucralfate and related compounds in a human intestinal epithelial (Caco-2) cell culture model of restitution on sheet migration across and adhesion to collagen I. Migration was quantitated across a collagen I matrix treated with sucralfate or related compounds and correlated with cell adhesion. Caco-2 motility was significantly and dose-responsively inhibited by sucralfate at therapeutic luminal concentrations. Sucrose octaacetate, the sucralfate backbone, and lactose octaacetate exhibited similar effects while the beta-bonded disaccharide maltose octaacetate had little effect. Sucrose itself slightly stimulated motility. Adhesion effects paralleled motility. Thus, sucralfate may inhibit intestinal epithelial motility by sterically interfering with adhesion to collagen I. A sucralfate analog with a lactose octaacetate backbone might retain growth factor binding without inhibiting enterocyte motility, perhaps improving its clinical efficacy.

Anti-Ulcer Agents↗

Mutation of the central nervous system neuroblast proliferation repressor ana leads to defects in larval olfactory behavior.

In the developing nervous system, interactions between glia and immature neurons or neuroblasts regulate axon pathfinding, migration, and cell division, and therefore affect structure and function. Glial control of neuroblast cell division has been documented by studies of the anachronism (ana) gene of Drosophila melanogaster. ana encodes a glycoprotein which, in the developing larval central nervous system, is secreted by glia that neighbor regulated neuroblasts. Mutations in ana lead to premature neuroblast proliferation in the larval brain. Examination of lacZ expression from an ana enhancer trap line as well as detection of the ana protein show that ana is also expressed in the larval antennal-maxillary complex (AMC) at all larval stages. As previously reported for the central nervous system, ana expression in the AMC appears to be confined to glial cells. Larval olfactory system function in ana mutants was assayed in a behavioral paradigm. When tested with the three different chemoattractants, third instar ana9 mutant larvae showed diminished olfactory response compared to controls. Examination of a second ana allele revealed aberrant olfactory response to ethyl acetate, demonstrating that more than one mutation in ana can give rise to abnormal larval olfactory behavior. Assays of early first instar ana9 mutant larvae revealed defective olfactory behavior, implying that the olfactory phenotype stems from early larval AMC and/or embryonic origins. This is consistent with proliferation analysis in the early larval AMC region which uncovered a significantly higher number of S-phase cells in ana9 mutants.

Alleles↗

Postoperative pain management.

Postoperative pain management is essential and must be approached as an integral part of the perioperative care. It should be systematic and based on sound physiologic and pharmacologic principles. The intra-operative management of pain is crucial, as there is perhaps an important role for preemptive analgesia. Because of its unique nature, pain is difficult to assess, but for good results adequate and repeated assessment are vital. The literature also points to the detrimental effects of inadequate pain control. There are a variety of methods available for pain management. In choosing a method, various factors need to be considered including physician skill, knowledge of analgesics and routes of administration, patient-related and clinical circumstances, the availability of an environment supportive of effective pain management, and the knowledge and skill of staff to assess and monitor patients. These need to be considered along with the risks and benefits and cost-benefit of the various drugs and techniques. The cornerstone of therapy is opioids, which can be administered by a variety of routes. The use of TEA with opioids and local anesthetics is highly beneficial, especially in high-risk patients. The aim should be to provide all patients a balanced analgesic regimen based on the identification of multiple mechanisms involved in postoperative pain.

Aged↗

Measuring vaccine efficacy for both susceptibility to infection and reduction in infectiousness for prophylactic HIV-1 vaccines.

Current Phase III trials are designed to assess only a vaccine candidate's ability to reduce susceptibility to infection or disease, that is, vaccine efficacy for susceptibility (VES). Human immunodeficiency virus (HIV) vaccination, however, may reduce the level of infectiousness of vaccinees who become infected, producing an important indirect reduction in HIV transmission even if the vaccine confers only modest protection against infection. We propose two approaches for augmenting the information of a classic trial for estimating protective efficacy that enable the additional estimation of the vaccine's effect on infectiousness, that is, vaccine efficacy for infectiousness (VEI). In the first augmentation, steady sexual partners of trial participants are recruited but not randomized to vaccine or placebo. Their infection status is monitored throughout the trial. In the second augmentation, the sexual partners are randomized. Through computer simulations and analytic methods, we investigate the feasibility and statistical properties of the augmented designs. Phase III prophylactic HIV-1 vaccines trials are currently being planned. Employment of the augmented designs described in this paper would not only provide estimation of VEI but also increase the precision of the VES estimator and the power to reject the null hypothesis of no vaccine effect.

AIDS Vaccines↗

Alternative forms of the human thioredoxin mRNA: identification and characterization.

Thioredoxin (TRX) is an ubiquitous and relatively conserved oxidoreductant enzyme which is involved in a multitude of redox reactions through the formation of reversible disulfide bonds. A recent report indicates the presence of novel isoforms of TRX proteins isolated from MP6 cell lines [Rosén et al., Int. Immunol. 7 (1995) 625-633]. In these isoforms, as evidenced from amino acid sequencing, several Lys residues of the wild-type sequence were replaced by Arg. Although the human genome contains several (isoformic) copies of the TRX gene, only one appears to be transcriptionally active [Kaghad et al., Gene, 140 (1994) 273-278]. As we characterized the isoforms of TRX mRNAs, we found that several MP6 TRX cDNA clones were devoid of the characteristic poly(A) tail. In order to increase the efficiency of isolating mRNAs without the poly(A) tail, we developed a novel procedure for exclusive capturing of a specific mRNA by magnetic beads coated with biotinylated antisense oligodeoxyribonucleotide. Using this method on MP6 cell total RNA, we isolated an additional truncated version of the TRX mRNA. This latter form does not produce any variant TRX enzyme, as an inframe stop codon truncates the product. This isoform was also present in mRNAs isolated from human placenta, leucocyte cells and Molt4 cells, the latter two being the progenitors of MP6 cells. From a thorough analysis of the sequence of the truncated TRX mRNA, we conclude that this variant originated from an event of altered splicing, as consensus splice sites were present in the normal TRX cDNA at precise positions.

Alternative Splicing↗