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Biomedical subjects

R Sinha

Publications and source records attributed to R Sinha.

At least 73 records · Page 4Linked to original sources
PubMed2000

Comparing odds ratios for nested subsets of dietary components.

BACKGROUND: In nutritional epidemiology, it is often of interest to disentangle the risk of disease associated with related foods or nutrients, where the food items are in a nested arrangement within a larger group. To compare odds ratios (OR) derived from a standard quantile-based analysis can be misleading since the amounts consumed may differ substantially for different dietary components. METHODS: The authors applied different logistic regression models on a case-control study concerning the risk of colorectal adenomas due to meat and its different subsets such as white meat, red meat and well-done red meat. RESULTS: By calculating OR for a fixed amount of intake, the authors suggest a method for partitioning the risk of one dietary item into that associated with increasingly detailed sub-components. A graph is presented for illustrating such partitions in terms of both addition and substitution effects. CONCLUSIONS: Odds ratios based on upper versus lower quantiles or percentiles are useful as they compare the risk between the upper and lower ends of the consumption range. A complimentary set of OR are those based on fixed amounts of consumption. These allow for direct comparisons between nested subgroups of dietary components, in order to disentangle the risk linked to specific groups of foods or nutrients.

Adenoma↗
PubMed2000

Effects of alcohol on baseline startle and prepulse inhibition in young men at risk for alcoholism and/or anxiety disorders.

OBJECTIVE: This study examined the hypothesis that a decreased reaction to alcohol and a deficit in prepulse inhibition (PPI) of the startle reflex are characteristics of male offspring of alcoholics without comorbid anxiety disorder. METHOD: Male offspring (N = 51) with a parental history of (1) alcoholism only, (2) anxiety disorder only, (3) alcoholism and anxiety disorder, and (4) no psychiatric disorder participated in an experiment examining the effects of alcohol on the acoustic startle reflex and on PPI. The experiment was carried out in two sessions in which subjects received an alcoholic beverage and placebo beverage on alternate days. RESULTS: The magnitude of startle was reduced by alcohol in each group. However, the degree of reduction was less in the offspring of alcoholics only compared to the other groups. In addition, PPI was reduced in the offspring of alcoholics only compared to the offspring of parents with no psychiatric disorder. CONCLUSIONS: A reduced reactivity to the effect of alcohol and a deficit in PPI might constitute vulnerability markers for alcoholism, but only in offspring of alcoholics without comorbid anxiety disorder.

Adult↗
PubMed2000

Alcohol and eating disorders: implications for alcohol treatment and health services research.

BACKGROUND: This paper focuses on the co-occurrence of alcoholism and eating disorders and the clinical implications for treating this comorbidity in women with alcohol use disorders. There is substantial literature that supports higher than expected rates of co-occurrence of these two disorders. In addition, there is evidence that the co-occurrence of alcoholism and eating disorders is more likely to occur in the presence of other psychiatric disorders. A critical analysis of the studies on the comorbidity of these disorders is conducted along with a review of the possible etiologic association between the two disorders. Crucial questions related to pharmacological and behavioral treatments for this subgroup of alcoholic women with eating disorders are raised from a health services research perspective. CONCLUSIONS: There is substantial evidence that alcoholism and eating disorders co-occur at high rates. However, as this review points out, several important research questions remain regarding both the clinical manifestations of each problem in women who are comorbid for both disorders and the treatment implications.

Alcoholism↗
PubMed1999

Effects of methylselenocysteine on PKC activity, cdk2 phosphorylation and gadd gene expression in synchronized mouse mammary epithelial tumor cells.

Methylselenocysteine (MSC), an organic selenium compound is an effective chemopreventive agent against mammary cell growth both in vivo and in vitro but its mechanism of action is still not understood. We have previously demonstrated that MSC is able to inhibit growth in a synchronized TM6 mouse mammary epithelial tumor cell line at 16 h time point followed by apoptosis at 48 h. The decrease in cdk2 kinase activity was coincident with prolonged arrest of cells in S-phase. The present set of experiments showed that cdk2 phosphorylation was reduced by 72% in the MSC-treated cells at 16 h time point. Expression for gadd34, 45 and 153 was elevated 2.5 to 7 fold following MSC treatment only after 16 h time point. In order to investigate a possible upstream target for MSC, we analyzed protein kinase C (PKC) in this model. Total PKC activity was reduced in TM6 cells by MSC (50 microM) within 30 min of treatment, both in cytosolic (55.4 and 77.6%) and membrane (35.2 and 34.1%) fractions for calcium-dependent and independent PKCs, respectively. PMA significantly elevated the PKC activity in membrane fraction (P < 0.01) and MSC inhibited this activation by more than 57%. The effect of MSC was selenium specific as selenomethionine and sulfurmethyl-L-cysteine (SMC) did not alter PKC activity either in cytosolic or membrane fraction. Immunoblot analysis showed that PKC-alpha was translocated to the membrane by PMA and MSC did not alter this translocation. PKC-delta was faintly detectable in membrane fractions of control and MSC-treated cells. MSC treatment slightly reduced levels of PKC-e (in cytosolic and membrane fractions) and PKC-zeta (cytosolic fractions). The data presented herein suggest that PKC is a potential upstream target for MSC that may trigger one or all of the downstream effects; i.e. the decrease of cdk2 kinase activity, decreased DNA synthesis, elevation of gadd gene expression and finally apoptosis.

Animals↗
PubMed1999

N-oxidative metabolism of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in humans: excretion of the N2-glucuronide conjugate of 2-hydroxyamino-MeIQx in urine.

2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), a major heterocyclic aromatic amine (HAA) formed in cooked meats, is metabolically transformed to mutagenic/carcinogenic intermediates. Cytochrome P4501A2 (CYP1A2)-mediated N-hydroxylation followed by phase II O-esterification by N-acetyltransferase (NAT2) are generally regarded as activation processes in which MeIQx and other HAAs are converted to genotoxic species. In this study, we determined the relationship between the activities of these two enzymes and the urinary excretion level of the N2-glucuronide conjugate of 2-hydroxyamino-MeIQx--N2-(beta-1-glucosiduronyl)-2-hydroxyam ino-3,8-dimethylimidazo[4,5-f]quinoxaline (N-OH-MeIQx-N2-glucuronide)--among healthy subjects fed a uniform diet containing high-temperature cooked meat. The individuals (n = 66) in the study ate meat containing known amounts of MeIQx, and urine was collected from 0 to 12 h after the meal. After addition of the deuterium-labeled internal standard to urine, N-OH-MeIQx-N2-glucuronide was isolated using solid-phase extraction and immunoaffinity separation. The isolated conjugate was converted to the deaminated product 2-hydroxy-3,8-dimethylimidazo[4,5-f]quinoxaline (2-OH-MeIQx) by heating with acetic acid. 2-OH-MeIQx and its deuterated analogue were derivatized to form the corresponding 3,5-bis(trifluoromethyl)benzyl ether derivatives and analyzed by capillary gas chromatography-negative ion chemical ionization mass spectrometry using selected ion monitoring procedures. The subjects in the study excreted an average of 9.4 +/- 3.0% (+/-SD) of an ingested dose of MeIQx as N-OH-MeIQx-N2-glucuronide in urine; the range varied from 2.2 to 17.1%. A significant correlation was found between the level of N-OH-MeIQx-N2-glucuronide in urine and the amount of MeIQx ingested (r(s) = 0.44; P = 0.0002). The excretion level of N-OH-MeIQx-N2-glucuronide in urine was not associated with the enzyme activities of NAT2 or CYP1A2. This is expected with the latter enzyme because the metabolism of MeIQx is first order and very rapid at the amounts ingested. The amount of N-OH-MeIQx-N2-glucuronide in urine was not correlated with the age or sex of the individuals. Our results indicate that biotransformation of MeIQx via CYP1A2 oxidation to form the N-hydroxylamine followed by N2-glucuronidation is a general pathway of MeIQx metabolism in humans; the variability in the excreted levels of N-OH-MeIQx-N2-glucuronide is probably due to interindividual differences in UDP-glucuronosyltransferase activity and/or excretion pathways.

Arylamine N-Acetyltransferase↗
PubMed1999

Role of well-done, grilled red meat, heterocyclic amines (HCAs) in the etiology of human cancer.

High-temperature cooking techniques and doneness level of red meat are linked to cancer of various sites, particularly colorectal cancer. In a colorectal adenoma study, we found an elevated risk for red meat consumption that was mainly due to an association with well-done/very well-done red meat. High-temperature cooking methods (i.e. grilling) were also associated with increased risk. We are currently using an HCA database linked to this questionnaire to estimate MeIQx, DiMeIQx and PhIP consumption and determine their association with risk of colorectal adenoma. Similar results on red meat doneness and fried meat were found in a case-control study of lung cancer. Thus, initial positive findings are stimulating the development of a more refined questionnaire instrument and its validation using food diaries, 24-h recalls, biomarkers of internal dose and direct food measurements. Furthermore, the use of these exposure assessment approaches are being used in large prospective studies world wide and should help clarify the role of doneness, cooking practices and pyrolysis products in the etiology of human cancer.

Carcinogens↗
PubMed1999

Quantification of the co-mutagenic beta-carbolines, norharman and harman, in cigarette smoke condensates and cooked foods.

Co-mutagenic beta-carbolines, such as norharman and harman, were quantified in mainstream and sidestream smoke condensates of six Japanese brands of cigarettes, and also in 13 kinds of cooked foods, using a combination of blue cotton treatment and HPLC. Norharman and harman were detected in all the cigarette smoke condensate samples. Their levels in the mainstream smoke case were 900-4240 ng per cigarette for norharman, and 360-2240 ng for harman, and in sidestream smoke, 4130-8990 ng for norharman and 2100-3000 ng for harman. These beta-carbolines were also found to be present in all the cooked food samples, at levels of 2.39-795 ng for norharman and 0.62-377 ng for harman per gram of cooked food. The observed concentrations are much higher than those found for mutagenic and carcinogenic heterocyclic amines (HCAs), suggesting that humans are exposed to norharman and harman in daily life to a larger extent than to HCAs.

Carbolines↗
PubMed1999

Biomonitoring of heterocyclic aromatic amine metabolites in human urine.

Human exposure to heterocyclic aromatic amines such as MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline) may be monitored by measuring the levels of the heterocyclic aromatic amine in urine. In order to investigate the contribution of N-oxidation to the metabolism of MeIQx in vivo, we developed a biomonitoring procedure for the analysis and quantification of the N2-glucuronide conjugate of 2-hydroxyamino-3,8-dimethylimidazo[4,5-f]quinoxaline in human urine. Subjects (n = 66) in the dietary study ingested a uniform diet of cooked meat containing known amounts of MeIQx, and urine was collected after consumption of the test meal. A method based on solid-phase extraction and immunoaffinity separation was used to isolate N2-(beta-1-glucosiduronyl)-2-hydroxyamino-3,8-dimethylimidazo++ +[4,5-f]quinoxaline and its stable isotope-labeled internal standard from urine. The isolated conjugate was converted to the deaminated product 2-hydroxy-3,8-dimethylimidazo[4,5-f]quinoxaline by treatment with acetic acid under moderate heating. 2-Hydroxy-3,8-dimethylimidazo[4,5-f]quinoxaline and the [2H3]methyl analog were derivatized to form the corresponding 3,5-bis(trifluoromethyl)benzyl ether derivatives and quantified by capillary gas chromatography-negative ion chemical ionization mass spectrometry employing selected ion monitoring procedures. The amounts of N2-(beta-1-glucosiduronyl)-2-hydroxyamino-3,8-dimethylimidazo++ +[4,5-f]quinoxaline recovered in urine collected 0-12 h after the test meal accounted for 2.2-17.1% of the ingested dose, with a median value of 9.5%. The variability in the proportion of the dose excreted among the subjects may be reflective of several factors, including interindividual variation in the enzymic activity of CYP1A2 and/or conjugation reactions of the N-hydroxylamine metabolite with N-glucuronosyltransferase(s).

Humans↗
PubMed1999

Well-done, grilled red meat increases the risk of colorectal adenomas.

Red meat or meat-cooking methods such as frying and doneness level have been associated with an increased risk of colorectal and other cancers. It is unclear whether it is red meat intake or the way it is cooked that is involved in the etiology of colorectal cancer. To address this issue, we developed an extensive food frequency questionnaire module that collects information on meat-cooking techniques as well as the level of doneness for individual meat items and used it in a study of colorectal adenomas, known precursors of colorectal cancer. A case-control study of colorectal adenomas was conducted at the National Naval Medical Center (Bethesda, MD) between April 1994 and September 1996. All cases (n = 146) were diagnosed with colorectal adenomas at sigmoidoscopy or colonoscopy and histologically confirmed. Controls (n = 228) were screened with sigmoidoscopy and found not to have colorectal adenomas. The subjects completed a food frequency questionnaire and answered detailed questions on meat-cooking practices. We used frequency and portion size to estimate grams of meat consumed per day for total meat as well as for meat subgroups defined by cooking methods and doneness levels. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression, adjusted for age, gender, total caloric intake, reason for screening (routine or other), and several established risk factors for colorectal adenomas or cancer, including the use of nonsteroidal anti-inflammatory drugs, physical activity, and pack-years of cigarette smoking. There was an increased risk of 11% per 10 g/day (or 2.5 oz/week) of reported red meat consumption (OR, 1.11; CI, 1.03-1.19). The increased risk was mainly associated with well-done/very well-done red meat, with an excess risk of 29% per 10 g/day (OR, 1.29; CI, 1.08-1.54) versus an excess of 10% per 10 g/day (OR, 1.10; CI, 0.96-1.26) for consumption of rare/medium red meat. High-temperature cooking methods were also associated with increased risk; 26% per 10 g/day (OR, 1.26; CI, 1.06-1.50) of grilled red meat and 15% per 10 g/day (OR, 1.15; CI, 0.97-1.36) of pan-fried red meat consumption. There was an increased risk of colorectal adenomas associated with higher intake of red meat, most of which was due to the subgroup of red meat that was cooked until well done/very well done and/or by high-temperature cooking techniques, such as grilling. These results are consistent with the hypothesis that carcinogenic compounds formed by high-temperature cooking techniques, such as heterocyclic amines and polycyclic aromatic hydrocarbons, may contribute to the risk of developing colorectal tumors.

Adenoma↗
PubMed1999

Stress-induced craving and stress response in cocaine dependent individuals.

Two laboratory studies were conducted to examine the effects of acute psychological stress on craving and stress reactivity in cocaine abusers. In the first preliminary study, we examined the effects of a speech stressor task and a personalized stress imagery task on self-reported craving and emotional state in ten cocaine abusers. Both stressors led to significant decreases in neutral and joy states, and significant increases in fear ratings as compared to baseline ratings. In addition, the stress imagery condition led to significant increases in cocaine craving and sadness and anger ratings, as compared to baseline. Thus, the personalized stress imagery task appeared to be more effective than the speech stress task in inducing craving in the laboratory. The second study examined the effects of stress imagery as compared to neutral imagery on cocaine craving, subjective anxiety and physiological responses in a second group of ten cocaine abusers. The stress imagery task once again produced significant increases in cocaine craving along with increases in heart rate, salivary cortisol and subjective anxiety ratings. These data are the first to document that acute psychological stress consistently increases craving for cocaine in cocaine abusers. The studies also provide a promising method for examining the association between stress and drug craving in the laboratory.

Adult↗
PubMed1999

Grayscale and pulsed Doppler characteristics of non-cirrhotic portal fibrosis: a preliminary report.

AIM: Non-cirrhotic portal fibrosis is a common cause of portal hypertension in India. Inspite of this there is no published data delineating the imaging findings in patients with this disease. The aim of this study was to evaluate Grayscale and pulsed Doppler findings of the portal venous system in non-cirrhotic portal fibrosis. MATERIALS AND METHODS: Grayscale and Doppler sonography was performed on 19 patients with clinically and histologically proven non-cirrhotic portal fibrosis. Portal venous flow was determined along with the portal venous diameter, congestive index of the portal vein, and the splenic index. Twenty normal control subjects were also studied. RESULTS: Doppler analysis revealed features of portal hypertension. These included increased portal venous flow, and congestive index (1062.1 +/- 199.7 vs 724.4 +/- 181.2; and 0.140 +/- 0.070 vs 0.049 +/- 0.011 respectively) when compared with the control group. Increased splenic index and dilatation of the portal venous diameter was also present (116.4 +/- 29.8 vs 45.8 +/- 7.0; and 14.3 +/- 1.5 vs 10.3 +/- 1.1 respectively). Grayscale findings demonstrated echogenic and thickened intrahepatic portal venous branches in 10 cases. Subcapsular atrophy of the liver was seen in three cases. Varices were identified in 15 cases. CONCLUSION: Patients with non-cirrhotic portal fibrosis have features of portal hypertension at the time of presentation. Ultrasonic findings that include echogenic, thickened portal venous tracts and subcapsular liver atrophy were frequently observed in such cases and were not seen in the control group.

Adult↗
PubMed1999

Diet, genetic susceptibility and human cancer etiology.

There is evidence that high penetrance hereditary genes cause a number of relatively uncommon tumors in the familial setting, whereas common cancers are influenced by multiple loci that alter susceptibility to cancer and other conditions. The latter category of genes are involved in the metabolism of carcinogens (activation, detoxification) as well as those that interact with dietary exposure. This paper will consider some of the basic principles in studying susceptibility genes and provide a few examples in which they interact with dietary components.

Alcohol Dehydrogenase↗
PubMed1999

False-positive radiographic diagnosis of breast implant rupture because of breast abscess.

A case of a periprosthetic abscess simulating breast implant rupture is presented. Both clinical findings and film-screen mammography suggested extravasation of a radiodense material adjacent to an implant. Ultrasonography was thought to confirm the extraluminal silicone. However, at surgery the mass was found to be a breast abscess that had herniated through the capsule. The double-lumen implant outer saline-filled chamber had deflated, but the silicone-containing inner chamber was intact. Magnetic resonance imaging would have distinguished between abscess and silicone.

Abscess↗
PubMed1999

Human cytochrome P4501A2.

CYP1A2, a member of the cytochrome P450 superfamily (CYPs), is involved in the metabolic activation of several carcinogens, among them aromatic and heterocyclic amines, nitroaromatic compounds, mycotoxins and estrogens. Several drugs are also metabolized by CYP1A2. Individual differences in CYP1A2 activity may thus influence individual susceptibility to cancer risk and the therapeutic efficacy of some drugs. In humans, CYP1A2 has been detected only in the liver, where it seems to be regulated by at least two mechanisms, one controlling constitutive levels of expression and another regulating inducibility. Wide interindividual differences in CYP1A2 activity have been described. They may be due to factors such as gender, race, genetic polymorphisms, and exposure to inducers. Higher activity has been shown in men than in women. Wide variation across racial/ethnic groups has been reported. Overall, slow and intermediate CYP1A2 metabolizers represent about 50% of Caucasians, while their frequency in Japanese subjects seems to be much lower. No nucleotide differences that could explain the phenotypic variability of the CYP1A2 gene have been found in any exons, exon-intron junctions, or 5'-flanking regions of the gene. However, two genetic variants have been identified which seem to be associated with CYP1A2 inducibility only. Induction of CYP1A2 activity has been reported as a consequence of cigarette smoking, dietary factors, several drugs, chronic hepatitis, and exposure to polybrominated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin. Several epidemiological studies have been conducted into the relationship between CYP1A2 activity, alone or in combination with other CYPs, and cancer risk. In the absence of a genotypic assay, only the CYP1A2 phenotype can be assessed at present. Many compounds have been tested as in vitro probes to assess CYP1A2 activity in humans. Currently, caffeine has the best potential for use in epidemiological studies: metabolites of caffeine after coffee consumption are measured as an index of CYP1A2 activity. Variable results have been obtained with caffeine-based methods, the use of some caffeine metabolite ratios having given bimodal or trimodal distributions while others have suggested normal or unimodal distributions. Although the epidemiological studies are limited because only phenotyping data are available, there is a suggestion of increased risk of colon cancer and bladder cancer in subjects with rapid CYP1A2 activity. A higher level of 4-aminobiphenyl-haemoglobin adducts has also been found in moderate smokers with rapid CYP1A2 phenotype than in subjects with slow activity.

Biotransformation↗
PubMed1999

Substance abuse and criminality.

Substance abuse issues and the law have become intricately linked over the years. This article reviews the current research underlying the association between substance abuse and crime, and provides an overview of the pertinent issues in conducting a substance abuse evaluation in the forensic context. The epidemiology of substance abuse and crime is reviewed, exploring the association between crime and specific psychoactive substances. Clinical considerations underlying the association are discussed, with specific attention paid to the pharmacological effects of psychoactive substances and to the role of substance use in individuals with serious associated psychopathology. Diagnostic and etiological issues that are important in differentiating substance abuse from criminality are considered in the context of conducting forensic evaluations. Finally, key components of a forensic substance abuse evaluation are presented.

Antisocial Personality Disorder↗
PubMed1999

Neuronal responses of periaqueductal gray to peripheral noxious stimulation.

Central pathways transmit pain from peripheral regions to one of the most important area of the descending pain modulatory system, the Periaqueductal gray (PAG). Independent discoveries in the past suggest that the PAG contains afferent input, output neurons and intrinsic interneurons. An attempt was made in the present study to find out the effects of more than one kind of noxious stimulus on the PAG neuronal activity. Experiments were conducted in rhesus monkeys and the effects of noxious mechanical, thermal and tooth-pulp stimulation on the activity of 14 neurons were studied. The neurons responded to more than one kind of noxious stimuli by increasing or decreasing its firing rate. No limb specificity could be identified and homogeneous distribution of the excitatory and inhibitory neurons was found.

Animals↗
PubMed1999

Hypothalamo-limbic involvement in modulation of tooth-pump stimulation evoked nociceptive response in rats.

The hypothalamo-limbic system has been implicated in recognizing the affective significance of pain and elicitation of related emotional responses. Several evidences from different studies support a role of these areas in endogenous analgesic mechanisms for pain modulation as elucidated by different pain tests in more than one animal model. In the above context, the aim of this study was to investigate the relative effectiveness of the pain modulatory action of hypothalamic and limbic structures in rat using similar stimulation parameters, and studying the effect on tooth pulp stimulation evoked jaw opening reflex (TP-JOR). To achieve the objective, unilateral stimulation of hypothalamic (lateral = LH; ventromedial = VMN; anterior = AH) and limbic areas (amygdala = AMYG; hippocampus = HIPP) was done on the TP-JOR test. A significant reduction in the amplitude of EMG recorded from the digastric muscle (dEMG) as a result of tooth-pulp stimulation was observed on stimulation of LH, VMN, AMYG and HIPP but not from AH. Also, the magnitude of this effect was almost similar from these areas. The results suggest that these areas (except AH) have an antinociceptive role in tooth-pulp stimulation evoked pain response.

Amygdala↗