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Biomedical subjects

R C Arora

Publications and source records attributed to R C Arora.

At least 19 recordsLinked to original sources

Serotonergic measures in suicide brain: the concentration of 5-HIAA, HVA, and tryptophan in frontal cortex of suicide victims.

Concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and tryptophan (TRP) were determined in the frontal cortex of individuals who died by suicide, homicide, accident, or the result of physical diseases. Females had significantly higher tryptophan concentrations than males. There was a significant correlation HVA and the interval between death to refrigeration of the body. Mean HVA levels were higher from noon to 5 PM. Suicide and homicide victims had significantly higher cortical HVA concentrations than those who died of physical disease but not accident victims. This was not accounted for by gender, age, postmortem interval from death to refrigeration of the body or to autopsy, specimen storage time, or drug effects. The ratio of HVA/5-HIAA was also significantly higher in suicides compared with those who died of physical disease. No differences in cortical 5-HIAA or tryptophan concentrations between the four groups were found. There were no differences in the levels of the three substances in violent and nonviolent suicides. There were no significant correlations between 5-HIAA, HVA and TRP concentrations in all subjects or any of the four subgroups. The implications of these findings for the role of serotonin and dopamine in suicide and violence are discussed.

Accidents

Platelet imipramine binding in depressed children and adolescents.

Kinetic constants of platelet imipramine binding were determined in youths with major depression, and a contrast group. Subjects actively depressed (N = 10) had significantly fewer imipramine binding sites (Bmax) (877 +/- 148 fmol/mg protein) than recovering depressives (N = 12) (1220 +/- 428 fmol/mg protein) and contrasts (N = 10) (1270 +/- 230 fmol/mg protein). Affinity constants (Kd) (1.14 +/- 0.36 nM, 0.97 +/- 0.31 nM, and 1.17 +/- 0.39 nM, respectively) were similar among the groups. Actively depressed males but not females had fewer imipramine binding sites than both their sex-matched comparison groups. Although actively depressed females' Bmax was significantly lower than recovering depressed and nondepressed males, neither age, Tannner stage, nor circannual rhythms influenced Bmax, but suicidality may be associated with low Bmax. A decrease in Bmax may be a state-specific marker of major depression in boys or associated with a depressive disorder with a suicidal history.

Adolescent

Serotonin uptake and imipramine binding in the blood platelets of obsessive-compulsive disorder patients.

14C-Serotonin (5-HT) uptake and 3H-imipramine binding (IB) were studied in the blood platelets of 20 obsessive-compulsive disorder (OCD) patients, 53 normal controls (5-HT uptake) and 32 normal controls (IB binding). The maximum number of binding sites (Bmax) was significantly decreased in OCD patients compared to normal controls, but there was no difference in the affinity for 3H-imipramine (Kd). The affinity for 5-HT uptake (Km) was also decreased in the OCD patients but the maximum velocity of 5-HT uptake sites (Vmax) was not significantly different in OCD patients and normal volunteers. There were trends for the Slowness Subscale of the Maudsley Obsessional-Compulsive Inventory (MOCI) to be positively correlated with the Km of 5-HT uptake (p = 0.094), whereas the Global Scale, Checking Subscale, and Doubting Conscientiousness Subscale of MOCI were negatively correlated with the Kd of IB (p = 0.066, p = 0.08, and p = 0.062, respectively). The results provide further evidence for the dysfunction of the serotonergic system in OCD.

Adult

Laterality and 3H-imipramine binding: studies in the frontal cortex of normal controls and suicide victims.

Serotonin [5-hydroxytryptamine (5-HT)]-sensitive imipramine binding (IB) was determined in the left and right hemisphere of frontal cortex of suicide victims and nonpsychiatric controls who died due to myocardial infarction or accident. The Kd (an inverse measure of affinity of 3H-imipramine to its binding sites) was significantly higher in left hemisphere than right hemisphere in normal controls. There were no differences in Bmax and Kd or Bmax between left hemisphere and right hemisphere in normals and suicides, respectively. These results do not support the finding of hemispheric asymmetry of 5-HT uptake as measured by IB (Bmax) in postmortem tissue from controls and suicide victims.

Carrier Proteins

Effect of 3,4-methylenedioxymethamphetamine on [3H]paroxetine binding in the frontal cortex and blood platelets of rats.

The effects of single or repeated administration of the racemic mixture of 3,4-methylenedioxymethamphetamine (MDMA; 20 mg/kg, s.c.) on the number (Bmax) of serotonin (5-HT) uptake sites as determined by [3H]paroxetine binding and the concentration of 5-HT and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were measured in the frontal cortex and blood platelets of rats 1 and 7 days following its administration. A single injection of MDMA significantly (P less than 0.05) decreased the number of [3H]paroxetine binding sites as well as the concentrations of 5-HT and 5-HIAA in the frontal cortex but not in platelets 7 days following administration. Repeated injections of MDMA (twice daily for 4 days) significantly (P less than 0.05) decreased the number of 5-HT uptake sites and the concentration of 5-HT and 5-HIAA in the frontal cortex but not in platelets 7 days following administration. Pretreatment with the 5-HT2/5-HT1C antagonist, ketanserin, inhibited the MDMA-induced decrease in 5-HT and 5-HIAA concentrations and the number of [3H]paroxetine binding sites in the frontal cortex 7 days following a single administration. These data are suggestive that blood platelets are less sensitive than brain tissue to the 5-HT-depleting effects of MDMA. The ability of ketanserin pretreatment to block MDMA-induced decreases in [3H]paroxetine binding sites in the frontal cortex is suggestive that 5-HT2/5-HT1C receptors may be involved in the neurotoxic effects of MDMA.

3,4-Methylenedioxyamphetamine

Serotonin2 (5-HT2) receptor binding in the frontal cortex of schizophrenic patients.

Serotonin2 (5-HT2) receptor binding was studied, using 3H-spiperone as the ligand, in post-mortem brain specimens obtained from schizophrenic patients (N = 11) and non-psychiatric controls (N = 11). The maximum number of binding sites (Bmax) was significantly decreased in schizophrenic patients as compared to normal controls. This difference did not appear to be due to neuroleptic treatment. No difference in Kd (an inverse measure of the affinity of 3H-spiperone to its binding sites) was observed between the two groups. However, studies with unmedicated schizophrenic patients are needed to draw any definite conclusion. The role of serotonergic processes in the psychobiology of schizophrenia is discussed.

Adult

Serotonergic measures in suicide brain: 5-HT1A binding sites in frontal cortex of suicide victims.

The density of 5-HT1A binding using 3H-8-hydroxy-2-(di-n-propyl-amino) tetralin (8-OH-DPAT) as binding ligand, was studied in human frontal cortex of suicide victims and normal controls who died due to medical disease or accidentally. There was no difference in the maximum number of binding site (Bmax) or Kd (an inverse measure of affinity) of 5-HT1A receptor binding sites between normal controls and the entire group of suicide victims. However, nonviolent suicides had significantly higher Bmax (22-25%) compared to both controls and violent suicides. A negative correlation between age and Bmax of 5-HT1A binding sites was found in male controls but not in female controls or suicide victims. This relationship was less apparent among the male controls over age 60.

8-Hydroxy-2-(di-n-propylamino)tetralin

Serotonin uptake in the blood platelets of Alzheimer's disease patients.

We determined serotonin (5-HT) uptake in the blood platelets of Alzheimer's disease (AD) patients and comparable age-matched normal controls. The maximum number of 5-HT uptake sites (Vmax) was significantly increased in mild and moderate AD patients, and a trend toward decreased V max was observed in severe AD patients as compared with normal controls. The Km of 5-HT uptake was negatively correlated with the Face-Hand Test (FHT) score of severely ill AD patients, whereas Vmax was correlated with the FHT score and the Mental Status Questionnaire score in the entire AD sample.

Aged

Dietary cholesterol induced changes in lipid profile in patients with nephrotic syndrome and chronic renal failure.

Fifteen patients with nephrotic syndrome (9 aged below 30 years), 6 patients with chronic renal failure and 26 healthy males (14 below 30 years) were studied. After estimating the basal serum levels of total cholesterol (STC), triglycerides (STG), high density lipoprotein (HDL) and low density lipoprotein (LDL), the patients were given a high cholesterol and high fat breakfast (containing 32 g fat and 527 mg cholesterol) for 7 days. Lipoprotein levels were again estimated on days 8 and 16. In the basal state, all patients with nephrotic syndrome had markedly elevated levels of STC and LDL. In patients aged below 30 years, STG and VLDL levels were also elevated, while HDL levels were similar in both the groups in comparison to their respective age group controls. In patients with renal failure, basal levels of all lipoproteins were similar to levels in controls. After the high cholesterol fat diet, there was an insignificant rise in all lipoprotein values in patients with nephrotic syndrome and renal failure. However, HDL levels rose significantly in patients with nephrotic syndrome aged below 30 years. Patients with nephrotic syndrome and chronic renal failure can safely be given high cholesterol and high fat diet despite abnormalities in lipid lipoprotein metabolism.

Adolescent

High density lipoprotein.

High density lipoprotein (HDL) is a discoidal particle comprising phospholipid, cholesteryl esters and several apolipoproteins. It serves in transporting cholesterol from the periphery to the liver by the process of "reverse cholesterol transport". Compatible with this is the finding that the mass of the tissue cholesterol pools is inversely related to plasma HDL concentration. The plasma levels of components of HDL are determined by various physiological and pathological factors. The serum HDL levels are lower with advancing age, male sex, and in genetically predisposed, obese, sedentary persons. The effect of diet on serum HDL levels is not established; mild to moderate alcohol intake is associated with high serum HDL level. The main diseases affecting serum HDL levels are uncontrolled diabetes mellitus, uraemia and hyperthyroidism. Anabolic steroids, sex hormones, oral contraceptives, hypocholesterolaemics and beta blockers have been shown to affect serum HDL level variably. There is increasing epidemiological evidence to show that high levels of HDL are protective against coronary heart disease (CHD). A low serum HDL cholesterol concentration (less than 35 mg/dl) is associated with a significant increase in coronary risk in both men and women. Guidelines published by the National Cholesterol Education Programme do not recommend routine measurement of HDL cholesterol and adaptation of therapeutic modalities aiming to raise the low HDL levels. They recommend hygienic means (i.e. smoking cessation, aerobic exercises and weight loss) to raise the HDL cholesterol levels.

Female

3H-imipramine binding in the blood platelets of normal twins.

3H-Imipramine binding (IB) was studied in the blood platelets of 13 pairs of monozygotic (MZ) and dizygotic (DZ) twins, and 15 pairs of unrelated normal volunteers, to determine if IB is under genetic control. The intrapair variance of Bmax (the maximum number of 3H-IB sites) was significantly smaller in MZ twins and unrelated control pairs than in DZ twins. The intraclass correlations (ICC) of Bmax were significant for all the pairs with no difference between these correlations. The ICC of the Kd (inversely related to the affinity for 3H-imipramine) of IB was significant only for the normal control pairs and the DZ twins. These results suggest that the kinetic constants of IB in blood platelets are not under genetic control and that interassay variance significantly affects the absolute values for Kd and Bmax of 3H-IB. The environmental and assay factors that influence 3H-IB may account for the numerous discrepancies in platelet 3H-IB between various research reports.

Adult

A study of dietary cholesterol induced changes in serum lipid lipoproteins in healthy male children, adolescents and middle aged volunteers.

The present study comprised of 16 healthy male subjects of 8-12 years (Group A), 18 adolescent males (13-19 years) (Group B) and 20 middle aged volunteers (45-55 years) (Group C), who were fed a high cholesterol high fat diet (HCFD) consecutively for seven days. The serum lipid changes were noted. The diet was then withdrawn. Seven days later the lipid changes were again recorded. At basal stage, serum total cholesterol (STC), high density lipoprotein (HDL) and low density lipoprotein (LDL) were significantly higher in group C in comparison to Group A. LDL/HDL ratio was significantly lower in Group C than that of Group A. Seven days after feeding of HCFD significant elevations occurred in all the lipid subfractions of Groups AB. The rise in STC was mainly because of predominant rise in HDL leading to a significant fall in LDL/HDL ratio. In Group C, elevations occurred in all the lipid fractions except HDL that showed an insignificant rise. LDL/HDL ratio was insignificantly affected. After withdrawal of HCFD, all the lipid levels returned to normal except in Group A, where STC and LDL remained elevated. The LDL/HDL ratio again increased significantly. In conclusion, the serum lipid lipoprotein behaviour in response to HCFD is qualitatively different in young persons as compared to middle aged persons.

Adolescent

Oral versus axillary temperatures in human volunteers.

We measured the oral and axillary temperatures of 100 individuals (including 40 females) in the medical wards. Twenty six had fever ranging from 37.3 degrees C to 40.5 degrees C while the rest had normal temperature. Although the oral temperature was higher than axillary temperature in all the cases, there was no correlation between the two; in one case the difference was as high as 1 degrees C. We conclude that while recording temperature the site must be clearly stated, and no attempt must be made to extrapolate the axillary to the oral temperature.

Adolescent

Post heparin lipoprotein lipase activity in patients of ischaemic heart disease and in controls.

A single high fat meal diet (66 gm fat) was given to 30 healthy males and 20 male patients of ischaemic heart disease (IHD). Ten minutes prior to the 4th postprandial hour, 500 units of heparin--a lipoprotein lipase (LPL) activator--was given, and its effect seen on serum triglyceride (STG) levels observed. Besides higher fasting STG levels, the decline in 4 hour post-prandial STG level was significantly lower in patients of IHD. One explanation for higher fasting STG values and prolonged postprandial lipaemia in these subjects could be deficient LPL activity.

Adult

Increased serotonin2 (5-HT2) receptor binding as measured by 3H-lysergic acid diethylamide (3H-LSD) in the blood platelets of depressed patients.

3H-Lysergic acid diethylamide (3H-LSD) binding, a putative measure of 5-HT2 receptor binding, was studied in the blood platelets of 29 depressed patients and 24 normal controls. The Bmax (maximum number of 3H-LSD binding sites) in the blood platelets of depressed patients was significantly greater than that of normal volunteers. This increase in Bmax was due to an increase in female depressed patients only. Bmax was significantly lower in female compared to male normal controls but there was no difference between male and female depressed patients. There was also no difference in Kd (an inverse measure of affinity of 3H-LSD binding to its sites) between normal controls and depressed patients. The correlations between Bmax of 3H-LSD binding and the Bmax of the 3H-imipramine binding site or the Vmax of 5-HT uptake sites were not significant. The role of serotonergic processes in the psychobiology of depression is discussed.

Adult

3H-imipramine binding in the frontal cortex of suicides.

Imipramine binding (desipramine- and serotonin-sensitive) was determined in the frontal cortex of suicide victims and nonpsychiatric controls who died due to medical disease or accidents. There were no differences in Kd or Bmax of imipramine binding between controls and suicides. The Kd and Bmax values of serotonin-sensitive imipramine binding were significantly lower than desipramine-sensitive imipramine binding, both in controls and suicides. There were significant correlations between Kd and Bmax of serotonin-sensitive imipramine binding and desipramine-sensitive imipramine binding in suicides but not in controls.

Adolescent

Serotonergic measures in the brains of suicide victims: 5-HT2 binding sites in the frontal cortex of suicide victims and control subjects.

The authors determined serotonin2 (5-HT2) binding in the frontal cortex of 32 suicide victims and 37 subjects who died from nonpsychiatric causes. The maximum number of binding sites (Bmax) and the affinity (Kd) were significantly higher in subjects who had committed suicide than in control subjects. However, there was no difference in Kd between these two groups after the influence of age, race, sex, and postmortem delay was covaried. The Bmax of subjects who had committed violent suicide was significantly greater than that of control subjects.

Adult