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Biomedical subjects

C Nath

Publications and source records attributed to C Nath.

At least 19 recordsLinked to original sources
PubMed2005

Interpretation of alpha-fetoprotein concentrations in cerebrospinal fluid of infants.

BACKGROUND: There are no published reference intervals for concentrations of alpha-fetoprotein (AFP) in the cerebrospinal fluid (CSF) of normal infants. The presence of abnormal concentrations of AFP in plasma or CSF may indicate the presence of a teratoma or a germ cell tumour with yolk sac elements. We measured CSF AFP in infants who did not have malignancy in order to determine its reference intervals. METHODS: AFP was measured in the CSF and/or plasma in 128 infants. Of these, 91 infants had CSF AFP measurements, 94 infants had plasma AFP measurements and in 60 infants AFP concentrations were determined in paired CSF and plasma samples. The patients ranged in age from 1 to 110 days. Both CSF and plasma AFP concentrations were measured by a microparticle enzyme immunoassay using an AxSYM analyser. RESULTS: Using ages corrected for prematurity, the median CSF AFP concentration for babies -69 to 31 days old was 61 kIU/L (5th-95th centile: 2-889 kIU/L), while the median CSF AFP concentration for infants 32 to 110 days was 1.2 kIU/L (5th-95th centile: 0.1-12.5 kIU/L). By age 6 weeks, the concentrations were close to those found in adult plasma and all CSF AFP concentrations from infants with a corrected age over 2 months were <3 kIU/L. CONCLUSION: We have defined reference intervals for CSF AFP concentrations in infants. These results may assist in the diagnosis of CNS tumours, particularly congenital CNS tumours containing yolk sac elements.

Enzyme-Linked Immunosorbent Assay↗
PubMed2004

Busulphan given as four single daily doses of 150 mg/m2 is safe and effective in children of all ages.

We examined the effects of busulphan (BU) dose and patient age on toxicity and outcome in 63 children with acute leukaemia given BUCY prior to allogeneic or autologous BMT. BU was administered as four single daily oral doses, based either on weight (4 x 4 mg/kg) or surface area (4 x 150 mg/m2). BU pharmacokinetic analysis was not used to dose adjust. The average daily (mg/kg) BU dose was 43% higher for the group given 150 mg/m2 compared to the 4 mg/kg dose group. This produced a median BU AUC 61% higher than with the 4 mg/kg dose. Only one child did not achieve full allogeneic donor engraftment. Regimen-related toxicity was low. Although younger children had faster BU clearance, the 4 x 150 mg/m2 dose ensured equivalent systemic exposure to BU, and resulted in a high frequency of engraftment without a significant increase in serious toxicity. BU, given as four single daily doses of 150 mg/m2, is appropriate and safe in all age groups of children. Given the reliable pharmacokinetics, low toxicity and high rate of allogeneic engraftment, there is no need for routine pharmacokinetic monitoring or dose modifications. This dosage regimen may be applicable for use with i.v. BU.

Bone Marrow Transplantation↗
PubMed2001

Profile of acetylcholinesterase in brain areas of male and female rats of adult and old age.

Inhibition of acetylcholinesterase (AChE)-metabolizing enzyme of acetylcholine, is presently the most important therapeutic target for development of cognitive enhancers. However, AChE activity in brain has not been properly evaluated on the basis of age and sex. In the present study, AChE activity was investigated in different brain areas in male and female Sprague-Dawley rats of adult (3 months) and old (18-22 months) age. AChE was assayed spectrophotometrically by modified Ellman's method. Specific activity (micromoles/min/mg of protein) of AChE was assayed in salt soluble (SS) and detergent soluble (DS) fractions of various brain areas, which consists of predominantly G1 and G4 molecular isoforms of AChE respectively. The old male rats showed a decrease (40-55%) in AChE activity in frontal cortex, striatum, hypothalamus and pons in DS fraction and there was no change in SS fraction in comparison to adult rats. In the old female rats the activity was decreased (25-40%) in frontal cortex, cerebral cortex, striatum, thalamus, cerebellum and medulla in DS fraction whereas in SS fraction the activity was decreased only in hypothalamus as compared to adult. On comparing with old male rats, old female rats showed increase in AChE activity in cerebral cortex, hippocampus and hypothalamus of DS fraction and decrease in hypothalamus of SS fraction. There was a significant increase in AChE activity in DS fraction of cerebral cortex, hippocampus, hypothalamus, thalamus and cerebellum in female as compared to male adult rats. However, no significant change in AChE activity was found in the SS fraction, except hypothalamus between these groups. Thus it appears that age alters AChE activity in different brain regions predominantly in DS fraction (G4 isoform) that may vary in male and female. These observations have significant relevance to age related cognitive deficits and its pharmacotherapy.

Acetylcholinesterase↗
PubMed2001

Behavioural and anti-psychotic effects of Ca2+ channel blockers in rhesus monkey.

The potential utility of Ca2+ channel blockers in the treatment of various psychiatric disorders has been recently suggested. In the present study, the behavioural and anti-psychotic effects of Ca2+ channel blockers were investigated in unrestrained rhesus monkeys (Macaca mulatta) living together in a colony. The different behaviours categorised as social, solitary and abnormal were video recorded and analysed. Graded doses of verapamil (5-20 mg/kg, i.m.) and nimodipine (7.5-30 mg/kg, p.o.) produced a mild decrease in social and solitary behaviour without producing any cataleptic posture in the tested monkeys. In order to determine potential antipsychotic effects, Ca2+ channel blockers were studied in the model of amphetamine-induced psychosis. Amphetamine, at the dose of 2 mg/kg, i.m., induced suppression of approach, contact, grooming, and feeding, whilst vigilance (checking), stereotyped behaviour and oral hyperkinesia were increased in the monkeys. Pre-treatment with verapamil (10 and 20 mg/kg, i.m.) significantly suppressed amphetamine-induced hypervigilance, stereotypy, oral hyperkinesia and tachypnoea but was unable to reverse other amphetamine-induced behavioural effects. Nimodipine showed insignificant anti-psychotic effects at both 15 and 30 mg/kg doses. These results suggest that verapamil has a definite antipsychotic effect without any extrapyramidal side effects and thus may be of clinical significance in the treatment of psychosis.

Amphetamine↗
PubMed2001

Role of central histaminergic system in lorazepam withdrawal syndrome in rats.

Effects of histaminergic agonists and antagonists were investigated on withdrawal signs in lorazepam-dependent rats. Physical dependence was developed by giving lorazepam admixed with the food in the following dose schedule (in mg/kg given daily x days): 10 x 4, 20 x 4, 40 x 4, 80 x 4, and 120 x 7. The parameters observed during the periods of administration of lorazepam and after its withdrawal were spontaneous locomotor activity (SLA), reaction time to pain, foot shock aggression (FSA), and audiogenic seizures. During the withdrawal period, the rats were divided into groups of 10 each. Control-withdrawal group did not receive any drug. The drugs (in mg/kg administered intramuscularly)--L-histidine (50), histamine-N-methyl (2), promethazine (10), pheniramine (10), astemizole (10), and thioperamide (1)--were given separately in other groups daily during the withdrawal period. The withdrawal signs in control group were hyperkinesia, hyperaggression, and audiogenic seizures. L-Histidine, precursor of histamine, and thioperamide, antagonist of H3 receptor, potentiated hyperkinesia, hyperaggression, and audiogenic seizures. Histamine-N-methyl, agonist of H3 receptor, and H1 receptor antagonists, promethazine and pheniramine, blocked all the withdrawal signs. Astemizole, a peripheral antagonist of H1 receptor, could not affect any withdrawal sign. It may be concluded that histamine H1 receptors are facilitatory and H3 receptors are inhibitory for benzodiazepine (BZD) withdrawal syndrome.

Acoustic Stimulation↗
PubMed2001

Managing insulin therapy.

Diabetic patients present a special challenge to your employees: Blood glucose levels require monitoring, medications must be administered appropriately, and all complications demand rapid assessment. The latest developments in insulin therapy will help to better manage this unique inpatient population.

Diabetes Mellitus, Type 1↗
PubMed2000

Immobilization stress-induced changes in brain acetylcholinesterase activity and cognitive function in mice.

In the present study, the effect of acute and chronic immobilization stress on brain acetylcholinesterase (AChE) enzyme activity and cognitive function in mice was investigated. Mice were immobilized by strapping for 150 min. One group of mice were only immobilized once (acute stress) while in another group mice were immobilized (150 min) daily for 5 consecutive days (chronic stress). Specific AChE enzyme activity (micromol min(-1)mg(-1)) was estimated by a spectrophotometric method in the whole brain of mice subjected to acute and chronic stress. In the acute stress group, AChE activity (0.24922 +/- 0.011) in the detergent-soluble fraction was found to be significantly decreased in comparison to the control group (0.33561 +/- 0.022). Chronic stress did not cause any significant change in AChE activity in the detergent-soluble fraction. In the salt-soluble fraction, AChE activity was significantly decreased only in the chronic stress group (0.08791 +/- 0.011) as compared to the control group (0.12051 +/- 0.011). A passive avoidance test was used to assess cognitive function. The transfer latency time (TLT) from a light to dark chamber was recorded in the control and acute stress groups (30 min after immobilization is over) on day 1 (Trial I) and the following day (Trial II). The acute stress group showed an increase (178%) in TLT from Trial I to Trial II, which was significantly higher than that of the non-stress control group (75%). In the chronic stress group, Trial I was undertaken 30 min after the last immobilization, i.e. on day 5 and 24 hr later, Trial II. However, the chronically stressed mice showed an increase (70%) in TLT similar to the control group. Thus this study shows that acute immobilization stress may enhance cognitive function in mice which may be attributed to a decrease in AChE activity leading to an increase in cholinergic activity in the brain.

Acetylcholinesterase↗
PubMed2000

The differential effects of calcium channel blockers in the behavioural despair test in mice.

Various studies have shown that calcium channel blockers (CCB) affect the release of central neurotransmitters including noradrenaline (NA) and 5-hydroxytryptamine (5-HT), which are involved in depression. The behavioural despair test was used to investigate the effect of CCB on depression. The mice were treated acutely with CCB. Verapamil (5, 10, 20, and 40 mgkg(-1), i.p.) and diltiazem (10, 20, and 40 mgkg(-1), i.p.) produced a dose-dependent increase in immobility time, indicating the facilitation of depression, while nifedipine (12.5, 25, and 50 mgkg(-1), i.p.) significantly decreased the immobility time, indicating an antidepressant activity. Verapamil ( 40 mgkg(-1), i.p.) and diltiazem ( 40 mgkg(-1), i.p.) blocked the antidepressant effect of desipramine, clomipramine, mianserin, and tranylcypromine, indicating the involvement of various mechanisms in the facilitatory effect of verapamil and diltiazem on depression. The antidepressant effect of nifedipine may be attributed to the blockade of presynaptic alpha -2-receptors (autoreceptors), as nifedipine blocked the clonidine-induced facilitation of depression.

Animals↗
PubMed2000

Effect of dopamine agonists and antagonists on the lorazepam withdrawal syndrome in rats.

1. The effects of dopaminergic agonists and antagonists were investigated on withdrawal signs in lorazepam-dependent rats. Physical dependence was developed by giving lorazepam admixed with food in the following dose schedules: 10 x 4, 20 x 4, 40 x 4, 80 x 4 and 120 x 7 mg/kg, daily for x days. 2. The parameters observed during the periods of administration of lorazepam and after its withdrawal were spontaneous locomotor activity (SLA), reaction time to pain, foot shock aggression (FSA) and audiogenic seizures. 3. During the withdrawal period, rats were divided into groups of 10 rats each. One group did not receive any drug and served as the control withdrawal groups. Three other groups received, separately, one of the following dopamimetic drugs: (i) 200 mg/kg per day, i.m., L-dihydroxyphenylalanine (DOPA; +50 mg/kg per day, i.m., carbidopa); (ii) 2 mg/kg per day, i.m., amphetamine; or (iii) 1 mg/kg per day, i.m., apomorphine. The remaining groups received one of the following dopamine antagonists: (i) 0.1 mg/kg per day, i.m., SCH 23390; (ii) 0.5 mg/kg per day, i.m., haloperidol; (iii) 0.5 mg/kg per day, i.m., centbutindol; and (iv) either 1 or 20 mg/kg per day, i.m., clozapine. 4. The withdrawal signs observed in the control group were hyperkinesia, hyperaggression and audiogenic seizures. 5. L-Dihydroxyphenylalanine (+ carbidopa), amphetamine and apomorphine potentiated hyperaggression and audiogenic seizures. The dopamine D2 receptor antagonists haloperidol, centbutindol and clozapine (at 20 mg/kg, i.m.) blocked all withdrawal signs. The D1 receptor antagonist SCH 23390 inhibited hyperkinesia and hyperaggression. The D4 receptor antagonist clozapine (at 1 mg/kg, i.m.) had no effect on any of the withdrawal signs. 6. It may be concluded that dopamine D2 receptors exert a dominant facilitatory influence, with partial contribution of D1 receptors, on the benzodiazepine withdrawal syndrome.

Acoustic Stimulation↗
PubMed1998

Role of cytokines in healing chronic skin wounds.

In the chronic wound, the normal cascade of inflammation, granulation and reconstruction phases of healing is interrupted. Cytokines are now known to orchestrate different biochemical mediators resulting in the restoration of the healing phases. Growth factors may play a significant role in stimulating wound repair by stimulating growth and proliferation. Since growth factors stimulate a variety of functions depending on cell type and wound stage and since wound-healing defects may occur at any phase of healing, a mixed combination of growth factors would be predicted to be more effective than a single factor. Factors that may modulate the action of growth factors include electrical stimulation, weight bearing, debriding and ischemia.

Animals↗
PubMed1998

U-shape relationship between change in dietary cholesterol absorption and plasma lipoprotein responsiveness and evidence for extreme interindividual variation in dietary cholesterol absorption in humans.

A possible relationship between change in dietary cholesterol absorption and plasma lipoprotein responsiveness was examined in 18 normal subjects fed low fat low cholesterol, high fat low cholesterol, and high fat high cholesterol diets. For the group, neither dietary cholesterol nor dietary fat affected the percentage dietary cholesterol absorption, whereas dietary cholesterol intake raised total and LDL-C and dietary fat raised total, LDL, and HDL-C. On a fixed diet there was approximately a 2-fold variation among subjects in percentage dietary cholesterol absorption. Subjects also varied in response to dietary cholesterol and fat with regard to dietary cholesterol absorption and plasma lipoprotein responsiveness. There was a U-shaped parabolic relationship between dietary cholesterol-induced percent change in LDL-C and the change in percentage dietary cholesterol absorption (R2 = 0.62, P = 0.005). A similar but weaker relationship characterized the responsiveness of HDL-C (R2 = 0.38, P = 0.05). For the group, increased cholesterol intake raised dietary cholesterol mass absorption from 1.6 to 4.6 mg/kg per day, but the range of increase was from 1 to 4.7 mg/kg per day. Increased fat intake also affected dietary cholesterol mass absorption with most subjects displaying a strong inverse relationship between fat intake and mass absorption (r = -0.77, P < 0.003). In summary: i) the percentage change in dietary cholesterol absorption in response to dietary cholesterol does appear to regulate diet responsiveness of LDL and HDL-C, and ii) the large variability in percent absorption and changes in percentage and mass absorption in response to dietary cholesterol suggest the presence of genetically determined differences among individuals in the regulation of dietary cholesterol absorption.

Adult↗
PubMed1997

Oligomycin sensitivity conferring protein (OSCP) of bovine heart mitochondrial ATP synthase: high-affinity OSCP-Fo interactions require a local alpha-helix at the C-terminal end of the subunit.

Earlier studies on oligomycin sensitivity conferring protein (OSCP) of bovine mitochondrial ATP synthase (F1Fo) indicated that a deletion mutant form (CD-10), lacking the last 10 amino acid residues (K181-L190), was unable to bind to the Fo segment, or reconstitute energy-linked reactions in OSCP-depleted F1Fo complexes [Joshi et al. (1996) Biochemistry 35, 12094-12103]. So far as known, the K181-L190 region of all mammalian species of OSCP harbors four charged residues at positions 181, 184, 187, and 188, while secondary structure predictions suggest that the K178-M186 region has a high propensity to form a helix [Ovchinnikov et al. (1984) FEBS Lett. 166, 19-22; Higuti et al. (1993) Biochim. Biophys. Acta 1172, 311-314; Grinkevich et al. ( 1994) Biol. Membr. 11, 310-323; Engelbrecht et al. (1991) Z. Naturforsch., C: Biochem., Biophys., Biol.,Virol. 46, 759-764]. Present studies were undertaken to clarify the role of individual amino acids in the K181-L190 region in OSCP-stimulated energy coupling. Our data show that simultaneous replacements of all four charged residues by uncharged but polar glutamines, or of K181-R184 by apolar alanines, had no significant influence either on the total alpha-helix content of the mutant forms or on the ability of mutant OSCPs to couple energy-linked reactions. However, a substitution of the K181-M186 region by six proline residues led to complete loss in the coupling activity of the resultant mutant. A detailed analysis of the 6-proline mutant form revealed that the variant was indistinguishable from WT OSCP with respect to expression characteristics, affinity for S-Sepharose, and ability to interact with F1, but was unable to complex with the Fo segment. These studies suggest that the global protein structure was not destabilized. The helix potential prediction analyses showed that the 6-proline OSCP displayed a marked decrease in the helix-forming propensity in the region corresponding to residues 175-190. Quantitative CD analyses to measure helical content demonstrated that both of the mutant forms 6-proline-OSCP and CD-10 had a somewhat lower alpha-helical content compared to WT protein, while synthetic peptides corresponding in sequence to the K178-L190 region displayed a high propensity to form a helix. Taken together, these results suggest that the C-terminal end of OSCP encompasses an alpha-helix which is crucial for high-affinity interactions of the C-terminal end of this subunit with Fo in the F1Fo enzyme.

Adenosine Triphosphatases↗
PubMed1997

Evidence for antiaggressive property of some calcium channel blockers.

The effect of calcium channel blockers on foot shock induced (aggression (FSA) were studied in mice. Verapamil, (10, 20 and 40 mg kg-1 i.p.) diltiazem (20 and 40 mg kg-1 i.p.) and nifedipine (25 and 50 mg kg-1 i.p.) significantly reduced fighting episodes. Diltiazem and nifedipine blocked the amphetamine induced facilitation of FSA, while verapamil blocked both amphetamine as well as physostigmine induced facilitation of FSA. These findings suggest that calcium channel blockers possess antiaggressive activity, which may be attributed to decrease in central dopaminergic and/or cholinergic mechanism.

Aggression↗
PubMed1997

Evaluation of inhibitory effect of diphenhydramine on benzodiazepine dependence in rats.

Effect of diphenhydramine was investigated on withdrawal signs in lorazepam dependent rats. Physical dependence was produced by giving lorazepam admixed with the food in the following dose schedule: 10 x 4, 20 x 4, 40 x 4, 80 x 4 and 120 x 7 (mg/kg, daily x days). The parameters observed during the periods of administration of lorazepam and after its withdrawal were spontaneous locomotor activity (SLA), body temperature, reaction time to pain, foot shock aggression (FSA) and audiogenic seizures. Diphenhydramine was administered orally in the dose schedules of once daily (10, 20 and 40 mg/kg) and twice daily (5, 10 and 20 mg/kg) in separate groups during the withdrawal period. The withdrawal signs observed in control group (without diphenhydramine) were hyperkinesia, hyperthermia, hyperaggression and audiogenic seizures. Hyperkinesia and hyperthermia were blocked in all the groups of diphenhydramine-treated rats. FSA was inhibited only by diphenhydramine (10 and 20 mg/kg) given twice daily. Audiogenic seizures were completely blocked by once daily (20 and 40 mg/kg) as well as twice daily (20 mg/kg) doses of diphenhydramine. It may be concluded that diphenhydramine exerts a protective effects on benzodiazepine withdrawal syndrome.

Acoustic Stimulation↗
PubMed1996

Oligomycin sensitivity conferring protein of mitochondrial ATP synthase: deletions in the N-terminal end cause defects in interactions with F1, while deletions in the C-terminal end cause defects in interactions with F0.

The structure/function relationships of oligomycin sensitivity conferring protein (OSCP) of bovine mitochondrial ATP synthase were studied by nested deletion mutagenesis, followed by analyses of the resultant OSCPs for their ability to restore partial reactions of ATP synthesis in OSCP-depleted F1-F0 complexes. Our results indicate that, from the N-terminus of OSCP, up to 13 amino acid residues could be deleted without any effect on OSCP coupling activity. However, deletion of 16 or more residues led to a slow decline in the ability of resultant mutant forms to restore ATP synthesis. Compared to the wild-type form of OSCP, deletion mutant ND-28 (deletion of residues 1-28) is 50% as active in its ability to reconstitute ATP-Pi exchange activity. Detailed analyses of mutant ND-28 revealed that it was able to bind to the membrane segment (F0) of ATP synthase and restore oligomycin-sensitive ATPase activity in OSCP-depleted F1-F0 complexes. However, it did not bind to soluble segment F1, nor did it confer cold stability to either soluble F1 or reconstituted F1-F0 complex. On the other hand, studies on nested deletions on the C-terminal end indicate that three residues could be deleted without compromising the energy-coupling activity of OSCP. However, truncations of five or more residues caused an impairment in the ability of resultant mutant forms to restore ATP-Pi exchange activity in OSCP-depleted complexes. Mutant CD-10 (deletion of amino acids 181-190) was completely ineffective as a coupling factor. Detailed analyses of this mutant revealed that the subunit was able to bind to soluble F1 segment and confer cold stability to the enzyme but was neither able to associate with the membrane segment (F0) nor able to reconstitute high oligomycin sensitivity in depleted F1-F0 complexes. We take these data to suggest that the N-terminal end of OSCP corresponding to residues G16-N28 is essential for binding of the coupling factor to soluble F1 but not for coupling the energy of proton translocation to the synthesis of ATP; on the other hand, the carboxyl-terminal end of OSCP containing amino acids K181-M186 is important for F0-OSCP interactions as well as for the coupling of the energy of delta microH+ during the synthesis of ATP. These results suggest a model for OSCP in which the N-terminus is associated with the F1 segment and the C-terminus is associated with the F0 segment, while the central part of the polypeptide forms three or more helices constituting the stalk in the intact F1F0 enzyme.

Adenosine Triphosphatases↗
PubMed1996

Effect of calcium channel blockers on withdrawal syndrome of lorazepam in rats.

Effects of calcium channel blockers were investigated on withdrawal signs in lorazepam dependent rats. Physical dependence was produced by giving lorazepam admixed with the food in the following dose schedule: 10 x 4, 20 x 4, 40 x 4, 80 x 4 and 120 x 7 (mg/kg daily x days). Parameters such as body weight, food intake, spontaneous locomotor activity (SLA), body temperature, reaction time to pain, foot shock-aggression (FSA) and audiogenic seizures were observed during the period of administration of lorazepam and after its withdrawal. Calcium channel blockers viz. verapamil, nifedipine and nimodipine in different doses were administered orally twice daily in separate groups during the withdrawal period. The withdrawal signs observed in control group (without calcium channel blockers) were hyperkinesia, hyperthermia, hyper-aggression and audiogenic seizures. The administration of verapamil (5-20 mg/kg), nifedipine (1.75-7 mg/kg) and nimodipine (5-20 mg/kg) during the withdrawal period of lorazepam showed dose dependent significant blockade of all the withdrawal signs. Audiogenic seizures were completely blocked by 20 mg/kg dose of verapamil and nimodipine while nifedipine was partially effective. It may be concluded that calcium channel blockers exert protective effects on benzodiazepine withdrawal syndrome.

Acoustic Stimulation↗