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Biomedical subjects

H Lal

Publications and source records attributed to H Lal.

At least 73 records · Page 4Linked to original sources

Effects of feeding low protein diet with and without leucine supplementation on protein status of lactating females and their pups.

Female rats were fed low protein diet (10% casein) either as such or supplemented with 3% leucine during pregnancy and lactation. Changes in litter size and the survival rate, growth and protein status of the pups were noted. The milk yield and hepatic and mammary gland protein status of the mothers were also studied. Feeding low protein diet reduced litter size, increased their mortality and resulted in poor growth of the pups. It also resulted in poor hepatic and mammary gland protein status of the mothers, as well as reduced their milk yield. On adding 3% leucine to 10% casein in the diet, the changes observed in the low protein group, did not alter in any manner.

Animals↗

Mianserin in the treatment of ethanol withdrawal in the rat: prevention of behaviors indicative of anxiety.

The present investigation was a pilot study to determine whether a single dose of mianserin, which produces long-term down-regulation of serotonin1C (5-HT1c) and 5-HT2 receptors, would prevent anxiogenic behaviors occurring during ethanol withdrawal as evaluated in the elevated plus maze. Male Long-Evans hooded rats were fed a liquid diet containing 4.5 percent ethanol for 4 days. Mianserin (20 mg/kg, i.p.) was injected on the morning of the third day of ethanol administration, or 48 hrs and 7 days prior to testing. When animals were tested either 12 hrs (acute withdrawal) or 5 days (protracted withdrawal) after the last dose of ethanol, anxiogenic behaviors were observed as a significant reduction in both percentage of open-arm entries and time spent on the open arms. In contrast, these anxiogenic behaviors were prevented by pre-injection with mianserin 48 hrs or 7 days prior to testing. Attenuation of this important symptom of ethanol withdrawal is of particular importance because, in addition to the nonaddicting properties of mianserin relative to current anxiolytics, the beneficial effects appear to be long lasting and can be achieved with a single dose.

Animals↗

Immunoglobulins IgG, IgM and IgA levels in preterm and small for date newborns.

Forty preterm [14 small for gestational age (SGA), 26 average for gestational age (AGA)] and 40 term (10 SGA and 30 AGA) babies were tested for immunoglobulins (Ig), G, M and A levels. IgG levels increased with gestational age from 922.00 +/- 14.00 mg/dl at 34 weeks to 1827.33 +/- 184.09 mg/dl at 40 weeks. Mean immunoglobulins were lower in SGA babies. IgG was 1029.59 +/- 122.80 mg/dl in SGA preterm babies and increased to 1262.00 +/- 200.0 mg/dl in 2 kg babies. IgM and IgA although increased with higher birth weight but rise was not statistically significant. More care to avoid infections in preterm and SGA babies, with lower immunoglobulin levels and less resistance, is recommended.

Birth Weight↗

Neurobehavioral biomarkers of aging: influence of genotype and dietary restriction.

Because of the importance of central nervous system (CNS) functions to productive capacity and quality of life, biomarkers of these functions will play a key role in evaluating the success of interventions targeting aging processes. The CNS biomarkers may also be useful for predicting aging in other systems and in the organism as a whole. Age-related behavioral changes, the products of CNS aging, have content and predictive validity with respect to human functional capacities and may, therefore, represent important "neurobehavioral" markers of functional aging. This article presents a discussion of some behavioral paradigms which are currently being considered as neurobehavioral biomarkers of aging in mice and the experimental approaches being employed in the assessment of their validity. Studies conducted in the authors' laboratory using dietary restriction and genetic comparisons to evaluate the validity of neurobehavioral biomarkers have revealed several methodological concerns, and hypothetical and empirical examples of these pitfalls are described and discussed. In spite of those concerns, it is concluded that approaches to validity using genetic comparisons and dietary restriction can be successfully implemented and should ultimately lead to identification of valid and useful neurobehavioral biomarkers of aging.

Aging↗

Animal models of drug withdrawal symptoms.

There have been few attempts to model subjective symptoms of drug withdrawal using animals as subjects. Two approaches for developing such models are reviewed. First, using drug discrimination methodology, it may be possible to train animals to detect the effects of withdrawal. This method has two difficulties: 1) the only discriminations trained to date involve precipitated withdrawal, and 2) the stimulus controlling behavior is difficult to specify. Second, withdrawal from many drugs of abuse produces the symptom of anxiety, and it seems likely that animal models of anxiety could be useful for studying drug withdrawal. This hypothesis has been explored most fully using subjects trained to detect the discriminative stimulus properties of the putative anxiogenic drug pentylenetetrazole (PTZ). Withdrawal from benzodiazepines or ethanol substitutes fully for PTZ, and withdrawal from cocaine, morphine, and nicotine substitutes partially for PTZ. Emerging data suggest that other animal models of anxiety may also be useful for detecting drug withdrawal. The final portion of this review examines a behavioral test that is very sensitive for detecting physical signs of withdrawal in animals. In subjects maintained on an operant baseline using food as a reinforcer, withdrawal from a drug of dependence frequently is associated with disruption of that operant behavior. For example, tetrahydrocannabinol and cocaine, drugs that are not traditionally seen as having significant withdrawal signs, produce disruption of operant responding when high-dose administration is terminated, and their readministration reverses this behavioral disruption. Based on the observation that withdrawal is associated with anxiogenic stimuli, we suggest a method to determine if disruption of operant behavior may be related to these stimuli.

Animals↗

The effects of 5-HT1B characterizing agents in the mouse elevated plus-maze.

Although the serotonergic system has been implicated in the modulation of anxiety states, the specific receptor subtypes that mediate these states require clarification. The effects of drugs that act preferentially at 5-HT1B receptors were evaluated on the behavior elicited in the elevated plus-maze, an animal model of anxiety. Variations in the intensity of light affected mouse behavior in the plus-maze; lower light intensity increased the entries to and time spent on the open arm in a manner similar to that seen with stress-attenuating circumstances. Opposite effects were observed in high light-intensity, similar to effects seen under elevated stress conditions. Chlordiazepoxide produced increased entries and time spent on the open arm, whereas pentylenetetrazol (PTZ) produced opposite effects. The preferential 5-HT1B agents TFMPP and mCPP exhibited a profile similar to PTZ. The effects of TFMPP in the plus-maze were reversed by chlordiazepoxide, but not by the benzodiazepine receptor antagonist flumazenil, which suggests that this effect is not directly mediated by benzodiazepine receptors. The decreased entries and time spent on the open arm of the maze following TFMPP or mCPP administration was possibly mediated by an antagonistic action at 5-HT1B receptors, since this effect was reversed by the selective 5-HT1B agonist CGS 12066B. The present study further demonstrates the utility of mouse behavior in the elevated plus-maze as a model for identifying anxio-modulatory substances.

Animals↗

Flumazenil improves active avoidance performance in aging NZB/BlNJ and C57BL/6NNia mice.

C57BL/6NNia and autoimmune NZB/BlNJ mice aged 12-14 months were tested for acquisition and retention of an active avoidance response following vehicle or flumazenil (40 mg/kg), a benzodiazepine antagonist. Acquisition and retention performance was improved in flumazenil-treated mice when compared with vehicle-treated mice, although the degree of improvement varied with the level of performance in vehicle-treated mice of each strain. The NZB/BlNJ mice, which generally performed more poorly than the C57BL/6NNia mice, showed the greater improvements following flumazenil. These results suggest that antagonism of benzodiazepine receptors leads to improved learning and/or memory performance in mice with spontaneous age-associated deficits.

Aging↗

Animal models of age-related dementia: neurobehavioral dysfunctions in autoimmune mice.

The development of strategies for treatment of Alzheimer's disease and other age-associated dementias is an important goal of research in the neurosciences. It is suggested that advances in understanding of the etiology of those disorders would provide the most obvious avenues to development of preventative treatments. Research findings from both clinical investigations and studies of animal models are presented which suggest a neuroimmunologic component in age-associated dementia. Clinical studies suggest an association between dementia and brain-reactive autoantibodies in subsets of patients with Alzheimer's disease. Studies of mice suggest that: 1) when compared with normal genotypes, mutant mice with accelerated autoimmunity show learning and memory impairments at earlier chronological ages; 2) the learning and memory deficits of autoimmune and normal mice are qualitatively similar; 3) the behavioral deficits of normal aged and autoimmune mice are sensitive to similar pharmacologic interventions. Overall, these findings suggest that intervention strategies targeting the immune system might be useful in the treatment or prevention of aging-associated dementia. Autoimmune mice would be useful as models for the development and testing of such immune-based interventions.

Animals↗

Cholinergic modulation of aged-like retention deficits in young autoimmune mice.

Separate age groups of autoimmune NZB/BINJ and non-autoimmune C57BL/BNNia mice were compared for habituation of locomotor activity and its retention over four separate testing sessions spaced at 24-hr intervals. A decline in locomotion (distance in cm) or in the time spent in the center zone as a function of sessions was taken to indicate retention for habituation to stimuli within the test apparatus. The time spent in the center zone decreased as a function of sessions in young and mature C57BL/6NNia mice but failed to show reliable between-session decreases in old (24-26-months) C57BL/6NNia mice. When compared with the old C57BL/6NNia mice, young NZB/BINJ mice showed similar impairments. Habituation of locomotion was present in all age groups of C57BL/6NNia mice, but absent in NZB/BINJ mice regardless of age. The retention impairments of 2-4 month old NZB/BINJ mice were attenuated when i.p. injections of 0.04-0.16 mg physostigmine/kg were given just following each habituation session. The effectiveness of physostigmine was substantially reduced when injections were delayed by 20 min or longer following each habituation session. The time-dependent reversal of the aged-like retention deficits by the cholinesterase inhibitor, physostigmine, suggests that cholinergic modulation of memory storage processes may be impaired in NZB/BINJ mice.

Aging↗

Serum and tear immunoglobulins in bacterial, fungal and viral corneal ulcers.

Serum and tear IgA, IgG and IgM levels were studied in patients with bacterial, fungal and viral corneal ulcers. In patients with viral corneal ulcers serum IgA and IgG levels were found to be significantly raised, while IgM concentration remained unaltered. In bacterial and mycotic ulcerations, serum IgA, IgG and IgM levels remained unaltered. All three immunoglobulins were found to be raised in tears of patients with viral corneal ulcers, while only IgA levels were found to be increased in bacterial and mycotic ulcerations.

Adult↗

Sensitivity of pentylenetetrazol discrimination increased by a stimulus fading technique.

The interoceptive stimulus produced by pentylenetetrazol (PTZ) is pharmacologically similar to anxiety and is used in a behavioral assay for anxiety-related stimuli (the PTZ model of anxiety). The stimulus fading technique was tested as a method to increase the sensitivity of this assay. Rats were trained with food-reward to press one lever after injection of PTZ and an alternate lever after saline. Rats initially learned the discrimination at a PTZ dose of 20 mg/kg. They were then trained with sequentially lower doses until they reliably discriminated a PTZ dose of 10 mg/kg. Substitution tests with other doses and drugs showed that, after the fading procedure, dose-response curves were shifted to lower doses for PTZ, Ro 5-3663, and nicotine Similarly, the dose of diazepam required to block the low dose of PTZ was lower than that required to block the higher dose of PTZ. These results indicated that the sensitivity of the discrimination was enhanced in rats trained to discriminate a lower dose of PTZ. Doses of nikethamide, cocaine, and yohimbine that did not substitute for the higher dose of PTZ also did not substitute for the lower dose. These data suggest that rats can be trained to discriminate a low dose of PTZ by the stimulus fading technique. Moreover, they suggest that this training method does not compromise the specificity of the discrimination.

Animals↗

The pentylenetetrazol-like interoceptive stimulus produced by ethanol withdrawal is potentiated by bicuculline and picrotoxinin.

We investigated whether the interoceptive discriminative stimulus (IDS) arising from ethanol withdrawal was related to decreased activity of the gamma-aminobutyric acid (GABA) system by determining whether the sensitivity of rats to the GABA antagonists was altered by chronic treatment with ethanol. Rats were trained to obtain food reward by responding on one lever following pentylenetetrazol (PTZ) and the other lever following saline. Whereas all of the trained rats selected the PTZ-appropriate lever after PTZ, no more than 50% of them selected this lever following an optimum dose of bicuculline or picrotoxinin. After either saline or diazepam (5 mg/kg), all of the rats selected the saline-appropriate lever. Ethanol (0.24 mol/kg/day) was then administered to the rats for 4 days via a nutritionally balanced liquid diet. Between 48 and 96 hours postethanol, 30% of the rats selected the PTZ-appropriate lever following saline, whereas selection of this lever was increased to 80% following either bicuculline or picrotoxinin. Thus, further antagonism of GABAergic activity increased the subjective effect of ethanol withdrawal. These data support the hypothesis that the PTZ-like IDS produced during withdrawal from ethanol is related to an ethanol-induced deficit in the activity of the GABA-benzodiazepine receptor-coupled chloride channel.

Animals↗

Serum enzymes in head and neck cancer. IV: 5-nucleotidase.

Serum 5-nucleotidase levels have been estimated in a group of 50 patients with head and neck cancer. The mean value was significantly higher in patients compared to the controls. In patients with non-malignant growths, the activity was comparable with the controls. The increase was higher in patients with proliferative lesions than those with ulcerative growths. Enzyme activity was found to be increased with the advancement in the stage of cancer. The rise was comparatively higher in patients with cervical metastasis. After radiotherapy, a gradual and significant reduction of serum 5-nucleotidase activity was observed.

5'-Nucleotidase↗

Effect of vitamin D administration during pregnancy on neonatal growth in the rat.

Groups of rats on commercial diet were injected 3,000 IU (group 2) and 7,500 IU (group 3) of vitamin D3 on the 10th day of pregnancy. Compared to control pups (group 1), the pups in group 2 and 3 weighed significantly more on the 10th, 20th and 28th day of age. At 28th day of age, study of the gastrocnemius muscle revealed significantly greater organ weight, protein, DNA and RNA contents, protein/DNA and RNA/DNA ratios in group 2 and 3 pups than in controls. In the liver, whereas all these indices were significantly increased in group 3 pups, only protein/DNA and RNA/DNA ratios were significantly increased in group 2 pups. Brain weight, its RNA content and RNA/DNA ratio were significantly greater in group 2 and 3 pups than in controls. The results suggest that vitamin D administration in pregnancy promotes soft tissue growth in the pups by enhancing cellular proliferation and hypertrophy.

Animals↗

Effect of aspartate and glutamate on experimental myocardial infarction in rats.

Cardiac necrosis was produced in rats by administering isoproterenol sulphate (85 mg/kg, sc for 4 days). The myocardial damage was proved by observing the elevated levels of serum aspartate amino-transferase, lactate dehydrogenase and creatine phosphokinase and the changes were confirmed by histopathology of the tissue. Both aspartate and glutamate (100 mg/kg, ip) significantly reduced the elevated levels of these enzymes. The average degree of cardiac necrosis produced in these rats when observed macroscopically and histologically was also found to be significantly reduced on pretreatment with aspartate and glutamate.

Animals↗

Serum magnesium levels in patients with head and neck cancer.

Serum magnesium levels have been estimated in 25 patients with head and neck cancer. The results have been compared with a group of 25 healthy controls. In cancer patients the mean value was significantly reduced when compared with the control group. A progressive, and significant, increase in serum magnesium concentration was observed following radiotherapy.

Adolescent↗

CGS 8216, a benzodiazepine receptor antagonist, enhances learning and memory in mice.

Mice pretreated with the benzodiazepine antagonist, CGS 8216 (2.5, 10, or 40 mg/kg, i.p.) learned a T-maze discrimination to a fixed performance criterion more rapidly than vehicle-treated mice. In retention tests conducted one week later, the drug-treated groups had better first-trial recall and greater difficulty reversing the previously trained maze habit when compared with controls, suggesting improved memory for the previously trained maze habit. The enhanced acquisition and retention following CGS 8216 was similar to that observed previously with another benzodiazepine antagonist, flumazenil (Ro 15-1788). It is postulated that CGS 8216 and flumazenil could act at benzodiazepine receptors to antagonize a tonic inhibitory influence of endogenous, diazepam-like, benzodiazepine receptor ligands on memory processes.

Animals↗