Biochemical studies in head and neck cancer.
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Adult↗
Biomedical subjects
H Lal
Publications and source records attributed to H Lal.
Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse.
This study was conducted in order to test the concept that oxidative damage is associated with aging and may be a factor in the modulation of life span in response to variations in caloric intake. Mice fed a diet that was 40% lower in calories (DR) than the ad libitum fed (AL) animals exhibited a 43% extension in average life span and a 61% prolongation in mortality rate doubling time. A comparison of AL and DR mice at 9, 17 and 23 months of age indicated that the protein carbonyl content in the brain, heart and kidney increased with age and was significantly greater in the AL than DR group in each organ at each of the three ages. Mitochondrial state 4 or resting respiratory rate increased with age in the AL, but not the DR group, and was also relatively higher in the former. The rates of mitochondrial superoxide and hydrogen peroxide generation increased with age and were higher in the AL than DR mice in all the three organs at each age. In contrast, there was no clear-cut overall pattern of age-related or dietary-related changes in antioxidant defenses provided by superoxide dismutase, catalase and glutathione peroxidase. Results suggest that mechanisms of aging and life span shortening by enhanced caloric intake are associated with oxidative damage arising from corresponding changes in mitochondrial oxidant production. Protein carbonyl content, and mitochondrial O2.- and H2O2 generation may act as indices of aging.
Aging↗
Serum leucine aminopeptidase in head and neck cancer.
Serum leucine aminopeptidase (LAP) activity was assayed in patients with head and neck cancer. The levels were found to be significantly higher than the controls. However, the rise in serum LAP was nearly the same in all patients studied, irrespective of the character or histopathology of the lesion but varied with respect to the site involved, i.e. from about 40 per cent in cancer of the hypopharynx to more than 100 per cent in cancer of the nasopharynx. Serum LAP activity was found to increase with the extent of the lymph node spread. After treatment the levels were found to be reduced.
Biomarkers, Tumor↗
Potential role of 5HT1C and/or 5HT2 receptors in the mianserin-induced prevention of anxiogenic behaviors occurring during ethanol withdrawal.
A single dose of mianserin (a 5HT1C/5HT2 antagonist), administered 1 hr, 48 hr, or 7 days before testing, was evaluated for its efficacy in alleviating or preventing the occurrence of anxiogenic behaviors observed during ethanol withdrawal. Other behavioral experiments using selected drug interactions were conducted to examine whether the effect of mianserin was related to a long-term modification of 5-hydroxy-tryptamine (5HT) receptor function. Rats were fed a liquid diet containing 4.5% ethanol for 4 days. They were tested on the elevated plus-maze (EPM) 12 hr (acute withdrawal) and 5 days (protracted withdrawal) after the last ethanol dose. Ethanol withdrawal induced a pattern of "anxiogenic" behavior that consisted of reduced activity (total entries) and a reduced proportion of open arm activity. Mianserin, injected as a single dose given either 1 hr (0.16-5 mg/kg, ip) before testing or given (20 mg/kg, ip) on the morning of the 3rd day of ethanol administration, i.e., 48 hr and 7 days before testing, dose-dependently prevented or reversed the ethanol withdrawal induced reduction in open-arm activity. In contrast, the 5HT1C/5HT2 receptor agonist (+/- )-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOl) did not affect behaviors in the EPM in ethanol-naive rats, nor in those undergoing ethanol withdrawal. However, although there was a marked tolerance to DOl-induced body shakes (a measure of 5HT2 function) during withdrawal, DOl reversed the action of mianserin in the EPM. The 5HT1 receptor agonist, 5HT2 receptor antagonist 1-naphthyl-piperazine (1-NP) reduced open-arm activity in ethanol-naive rats and this action was enhanced during withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)
Alcohol Withdrawal Delirium↗
Anxiogenic effect of disulfiram evaluated in an animal model.
The present experiment was designed to determine whether disulfiram produced an interoceptive discriminative stimulus (IDS) in rats similar to that exhibited by the anxiogenic drug pentylenetetrazol (PTZ). Rats were trained to discriminate PTZ (20 mg/kg IP) from saline, according to an FR10 schedule of food reinforcement. After training criteria had been met, discrimination testing revealed that disulfiram (100 mg/kg, IP) produced a PTZ-like IDS that fully substituted for PTZ 4 hours after injection, decaying to baseline values by the third day. The metabolite of disulfiram, diethyl dithiocarbamate (100 mg/kg, IP), followed much the same temporal pattern, but only showed partial substitution for PTZ. When ethanol (1 g/kg, gavage) or the monoamine oxidase inhibitor pargyline (50 mg/kg, IP) were administered in combination with disulfiram, no significant change of the PTZ-like stimulus was observed. Pargyline (100 mg/kg, IP) or acetaldehyde (200 mg/kg, IP), given alone, did not significantly substitute for PTZ. These data show that disulfiram produces an IDS in rats similar to that produced by other anxiogenic drugs. These data also suggest that the mechanism by which disulfiram produces its anxiogenic effect may not be entirely based upon the disulfiram metabolite diethyl dithiocarbamate, elevated acetaldehyde levels or stimulation of the catecholaminergic system.
Acetaldehyde↗
Conflicting evidence regarding the efficacy of ondansetron in benzodiazepine withdrawal.
These experiments tested the efficacy of the 5-hydroxytryptamine3 antagonist ondansetron (OND) in reversing various aspects of benzodiazepine withdrawal in rats. Three tests were used in which the benzodiazepine antagonist flumazenil was administered to rats receiving chronic administration of chlordiazepoxide. In one test, the elevated plus-maze, flumazenil produced a reduction in time spent in the open arms of the maze; OND completely reversed this effect of flumazenil in a dose-related fashion. However, OND failed to block the effects of the anxiogenic drug pentylenetetrazole (PTZ) in the elevated plus-maze. In a second test, rats were trained to discriminate PTZ. After chlordiazepoxide, flumazenil substituted for PTZ; OND failed to block flumazenil. In a third test, rats maintained on a chronic base line of chlordiazepoxide were trained to discriminate flumazenil from vehicle. In this discrimination, PTZ substituted for flumazenil, and pentobarbital blocked the flumazenil stimulus; OND, however, failed to block the flumazenil stimulus. In a separate set of experiments, OND also failed to reverse the suppression of responding produced in a conditioned emotional response paradigm. Thus, some data from the elevated plus-maze are consistent with the hypothesis that benzodiazepine withdrawal shares common effects with other stimuli known to be anxiogenic, and that OND blocks this aspect of withdrawal. However, all other data are inconsistent with the hypotheses that OND is anxiolytic or has efficacy in reversing benzodiazepine withdrawal. We suggest that ondansetron is likely to have minimal efficacy in humans for the treatment of sedative-hypnotic withdrawal.
Animals↗
Evaluation of anxiolytic action of ondansetron in rats during withdrawal from chronic chlordiazepoxide.
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Animals↗
Learning and memory-enhancing effects of Ro 15-4513: a comparison with flumazenil.
Synthetic benzodiazepines produce an anterograde amnesia, which can be reversed by selective benzodiazepine antagonists or inverse agonists. It has therefore been suggested that the memory-enhancing effects of the antagonists are due to antagonism of an endogenous "benzodiazepine-like" endocoid. If the memory-enhancing effects of the benzodiazepine antagonists are determined predominantly by the antagonism of such endogenous benzodiazepine-ligands, then it could be hypothesized that administration of an inverse agonist, which produces effects functionally opposite to those of benzodiazepine agonists, may also mimic the effects of benzodiazepine antagonists but not produce effects greater than those of the pure antagonists. The purpose of the present study was therefore to investigate the memory-enhancing effects of the benzodiazepine inverse agonist, ethyl-8-amido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5a] [1,4] benzodiazepine-3-carboxylate (Ro 15-4513) in young HSD:(ICR)BR mice and to compare these effects with those of the benzodiazepine antagonist, flumazenil. Pretraining injections of flumazenil and Ro 15-4513 (2.5 and 10.0 mg/kg) enhanced equally, both the acquisition and the retention of a task for 1 week requiring mice to discriminate the correct arm of a T-maze, to avoid a mild electric shock. Pretreatment with Ro 15-4513 also dose-dependently protected the animals from experimental amnesia, induced by the cholinergic receptor antagonist, scopolamine in a second model of memory, in which mice were required to passively avoid a dark chamber after shock. In contrast, Ro 15-4513, injected prior to daily active avoidance sessions, failed to significantly improve either the acquisition or retention performance.(ABSTRACT TRUNCATED AT 250 WORDS)
Amnesia↗
Serum immunoglobulin E levels in children with chronic tonsillitis.
Serum immunoglobulin E (IgE) levels were estimated by ELISA in 50 children with chronic tonsillitis before and after tonsillectomy. When compared with the control group, mean serum IgE concentration was found to be significantly higher in children with chronic tonsillitis (P less than 0.001). After tonsillectomy the levels returned to normal.
Adolescent↗
Effect of adenosine and inosine on carbon tetrachloride-induced liver damage in rats.
Liver damage induced in rats by carbon tetrachloride (CCL4) was obvious macroscopically as well as microscopically in stained sections. Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transpeptidase (gamma-GT) were also significantly raised. Adenosine and inosine effectively countered the damage when these were given before and during the period during which CCl4 produces the typical damage. The beneficial effect was seen in biochemical as well as pathological studies.
Adenosine↗
Protracted withdrawal: sensitization of the anxiogenic response to cocaine in rats concurrently treated with ethanol.
Rats were trained to respond on one lever following an injection of saline and the alternate lever after the anxiogenic drug pentylenetetrazol (PTZ 20 mg/kg), according to a fixed ratio (FR10) schedule of food reinforcement. The trained animals were then administered dependence-producing regimens of either cocaine (20 mg/kg, [IP], three times daily for 7 days) or ethanol (mixed 4.5% w/v with sweetened liquid diet given for 5 days). Separate groups of trained rats were given either subthreshold regimens of cocaine (20 mg/kg, IP, three times daily for 5 days), ethanol (2.25% w/v of the diet given for 5 days), or both. Additional groups were matched for control groups. After discontinuation of these regimens, rats were administered test injections of either saline or cocaine, and tested for elicitation of the PTZ-stimulus at selected intervals of withdrawal. After a saline injection, maximum elicitation of the PTZ-stimulus was observed 12 hours following chronic treatment with the higher dose of ethanol, and 120 hours following longer treatment with cocaine. During those periods of withdrawal when a saline injection failed to produce a PTZ-like stimulus, a test injection of cocaine (10 mg/kg) elicited the PTZ-stimulus in the ethanol withdrawn rats, although only partially eliciting the PTZ-stimulus in the cocaine withdrawn group. In the pair-fed controls, or rats withdrawn from the smaller dosage of either ethanol or cocaine, the test dose of saline or cocaine did not elicit the PTZ-stimulus; only 30% of rats selected the PTZ-appropriate level at the highest dose of cocaine tested (10 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
Alcoholism↗
Nutritional requirements in infancy.
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Humans↗
Detection of Chlamydia trachomatis antigen by enzyme immunoassay in patients with pelvic inflammatory disease.
In 27 out of the 60 women clinically suspected to have pelvic inflammatory disease (PID) studied, the C. trachomatis antigen titre was found to be higher than the cut-off value. Since the presence of C. trachomatis antigen was detected in 45 per cent of women, it is suggested that all the PID patients may be investigated by ELISA to confirm the role of C. trachomatis as the etiological agent.
Adult↗
Serum gamma glutamyl transpeptidase in head and neck cancer.
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Female↗
Modulation of benzodiazepine agonist and inverse-agonist receptor binding by GABA during ethanol withdrawal.
1. The present study examined the capacity of GABA to modulate flunitrazepam and Ro15-4513 binding to putative GABAA receptors. Binding was measured in distinct brain regions both before and during selected periods of withdrawal from ethanol. 2. Rats were fed a nutritionally complete liquid ethanol (4.5% w/v) diet for 4 days and at various times after the last dose of ethanol (0, 12, 24, & 72 hr), rats were sacrificed and extensively washed brain membrane fractions were prepared. 3. Competitive inhibition of 3H-flunitrazepam binding by either flunitrazepam or Ro15-4513 (10(-10)M to 10(-7)M) was performed in the absence and presence of GABA (10(-5)M). In the presence of GABA, the apparent affinity for flunitrazepam was increased approximately 1.7 fold and the apparent affinity for Ro15-4513 was decreased by 1.7 fold. 4. No alteration in the capacity of GABA to modulate flunitrazepam or Ro15-4513 affinity (e.g. GABA-shift) was observed in cortical membrane preparations either 12 or 72 hr following ethanol cessation. 5. Further, no changes in GABA-modulation of flunitrazepam binding was evident 0, 12, 24, or 72 hr after the last ethanol dose in membranes prepared from cortex, hippocampus or cerebellum. 6. Therefore, results from the present study indicate that the capacity of GABA to modulate receptor affinity for benzodiazepine agonists and inverse-agonists in rat cortex, hippocampus or cerebellum is not altered during withdrawal from chronic ethanol.
Animals↗
Plasma prolactin and insulin changes on feeding leucine supplemented diet in rats.
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Animals↗
Tear lysozyme levels in bacterial, fungal and viral corneal ulcers.
Low levels of tear lysozyme were observed in patients with infective corneal ulcers, when compared with controls. Lowest levels were seen in patients with bacterial corneal ulcers. The levels of tear lysozyme showed a corresponding decrease with the increase in Schirmer test values; meaning thereby, that in ocular conditions associated with increased rate of tear flow, the lysozyme content in tears tends to be low.
Adult↗
Effect of vitamin D supplementation in lactating rats on the neonatal growth.
In lactating rats consuming a commercial diet adequate in calcium, phosphorus and vitamin D, the effect of supplementation of 3000 IU and 7,500 IU of vitamin D3 on the lactational performance of the dams and soft tissue and skeletal growth in the pups has been investigated. On 28th day of age, the pups in the supplemented groups were significantly heavier than in the control group. Study of the indices of cellular growth in the liver and gastrocnemius muscle revealed that the increase in the soft tissue weight was due to a significant increase in protein, RNA and DNA contents (cellular hyperplasia) without any change in protein/DNA ratio (cell size). In the tibia, compared to controls, the dry bone weight and ash weight were more in the supplemented groups, but ash weight/dry bone weight ratio was not altered. The improvement in the neonatal growth was most probably due to the greater milk yield observed in the dams in supplemented groups and not due to any anabolic effect in the pups since direct administration of 500 IU or 1,000 IU of vitamin D3 in 10 day old pups did not increase their body weight.
Animals↗