Biomedical subjects
Publications and source records attributed to H Lal.
Serum adenosine deaminase (ADA) levels were estimated in a group of 40 patients with head and neck cancer. The mean value was significantly higher in patients compared to controls. The increase was higher in cases of ulcerative growths than of proliferative growths, and activity was increased with advancement in the stage of the cancer. After radiotherapy, a gradual and significant decrease in serum ADA activity was observed.
Gamma glutamyl transpeptidase (GGTP), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) were measured serially in the serum and cerebrospinal fluid (CSF) of 22 patients with fresh stroke and an equal number of age- and sex-matched healthy control subjects. It was observed that levels of these enzymes in the CSF of control subjects were very low but were significantly elevated (p less than 0.001) in both serum and CSF in patients with stroke. The elevation was greater in the CSF than in the serum and was maximum during the first four days of stroke. Thereafter, the enzymatic activity declined. Of all these enzymes, GGTP in CSF correlated best with the clinical picture. It was possible to differentiate between the ischemic and hemorrhagic type of stroke on the basis of CSF levels of GGTP (greater than 60.0 units in hemorrhagic stroke). There was no correlation between GGTP levels in CSF and serum or among GOT, GPT, and GGTP in CSF. It can be concluded, therefore, that estimation of GGTP in CSF is helpful not only in predicting the degree of cerebral damage and functional outcome of the patient following stroke but also in differentiating the type of stroke.
The extent to which immune processes contribute to senescence-related neurological/behavioral impairment was examined using an adoptive transfer procedure. C57BL/6 mice aged 22 to 24 months showed impaired ability for acquisition of an active avoidance response when compared with younger mice aged 3 months. An immunofluorescence assay of the sera of these mice indicated that only sera from the senescent mice reacted with brain antigen. When tested three months following irradiation and receipt of bone marrow/spleen cell suspensions from senescent mice, young mice showed senescence-like serum-brain reactivity and declines in their abilities to acquire learning. Young control mice receiving cell suspensions from age-matched donors showed no evidence of serum-brain reactivity or learning deficits, suggesting that impaired learning was related to acquisition of aged immunity and not a nonspecific effect of the transfer procedure. These findings indicate that immune processes may be involved in the etiology of senescence-related neurological/behavioral dysfunctions.
Separate age groups of C57BL/6 and autoimmune New Zealand Black (NZB) mice were compared for diazepam-induced ataxia and barbiturate-induced loss of righting reflex. Between 1 and 3 months of age, both strains showed a similar age-related decrease in ED50 for diazepam-induced ataxia. However, between 3 and 12 months the decrease in ED50 was markedly greater in NZB mice. In contrast, age-related increases in the durations of loss of righting reflex following hexobarbital or barbital were similar in both strains. The results suggest that NZB mice show relatively accelerated age-related increases in sensitivity to benzodiazepine, but not to barbiturates.
Rats were trained on an FR10 schedule of food reinforcement to press one lever after pentylenetetrazol (PTZ), 20 mg/kg, IP, and an alternate lever after saline. After acute nicotine, 0.64 mg/kg, SC, 35% of the rats pressed the PTZ-lever. Diazepam, 5 mg/kg, IP, blocked the stimulus produced by PTZ, and mecamylamine, 5 mg/kg, IP, blocked the stimulus produced by nicotine. Training was then suspended and rats were treated with nicotine, at 8-h intervals, 0.64 mg/kg on the 1st day, and 1.25 mg/kg on subsequent days, for 21 days. To determine whether nicotine withdrawal substitutes for the stimulus produced by PTZ, rats were tested with saline at various times after chronic nicotine injections. Data from this part of the study were replicated in another group given nicotine for 15 days. Saline at 8 h after nicotine (five determinations each group) produced a small but stable degree of PTZ lever selection (35 +/- 4%). At 48 h after termination of nicotine treatment, the percentage of rats selecting the PTZ lever (50%) was greater than that in a control group tested after an equivalent period without training. The PTZ-like stimulus detected after chronic nicotine was not altered by mecamylamine, was additive with PTZ, and was blocked by diazepam. These data suggest that withdrawal from chronic nicotine produces a weak PTZ-like stimulus, which can be antagonized by an anxiolytic drug.
Serum phosphohexose isomerase (PHI) levels were estimated in 28 patients with head and neck cancer. The mean value was significantly higher when compared to the controls. There was no difference in mean PHI value with respect to the character of the lesion or with the histopathological type of growth. The activity was increased with the advancement of the stage of cancer. With radiotherapy, a gradual and significant decrease in serum PHI activity was observed.
The possibility that autoimmunological disorders involving neuronal constituents as autoantigens can result in measurable behavioral impairments prompted the behavioral analysis of the New Zealand black (NZB) mouse strain, known to have high levels of brain-reactive antibodies. Sensorimotor competence and performance in tasks requiring learning and memory were assessed in 7-10-month-old NZB and contrasted with those of CFW mice. The NZB mice showed pronounced deficits in performance of passive and active shock avoidance responses. These deficits could not be accounted for by the slight sensorimotor disadvantage of NZB mice relative to CFW mice. No difference between the two mouse strains was seen in passive avoidance behavior at 1.5 months of age. It is concluded that NZB mice display a behavioral deficit related to cognitive dysfunction and that autoimmune mechanisms may be involved in the etiology of this deficit. Such behavioral disturbances produced by an autoimmune mechanism may have relevance for the neurological declines observed in aging, since the incidence of autoimmune disorders increases markedly in old age.
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Treatments which increase gamma-aminobutyric acid (GABA) neurotransmission or those which cause stimulation of benzodiazepine receptors, produce anxiolytic effects; but the converse (anxiogenic) effects have not been reported after suppression of either system alone. We report here that simultaneous inhibition of these two systems produces anxiogenic effects. After partial depletion of GABA by isoniazid, the benzodiazepine antagonists, RO 15-1788 and CGS8216, produced pentobarbital reversible anxiogenic effects in the pentylenetetrazol discrimination assay. These results support the hypothesis that GABA and endogenous anxiolytics mutually facilitate modulation of anxiety. They also indicate that there may exist endogenous anxiogenics which act at non-benzodiazepine recognition sites.
Rats were trained to discriminate the stimulus properties of either cocaine or clonidine using a food reinforced two-lever choice paradigm. After training, cocaine was generalized to the cocaine lever in a dose-dependent manner, and clonidine was generalized to the clonidine lever in a dose-dependent manner. Yohimbine, an alpha-2 antagonist, blocked the clonidine stimulus but not the cocaine stimulus. Cocaine was not generalized to the clonidine stimulus; however, clonidine was generalized to the cocaine stimulus, and this generalization was blocked by yohimbine. The one-way generalization of clonidine to cocaine suggests that clonidine has at least two discrete stimulus components: a major component that is not cocaine-like, and a minor component that can be detected by cocaine-trained subjects. In addition, the yohimbine blockade data suggest that both components of the clonidine stimulus are mediated via alpha-2 receptors.
Fish fingerlings (Cirrhina mrigala) exposed to 0.005 ppm (25% of LC50) concentration to detergents (linear alkyl benzene sulfonate) showed marked behavioral changes and distorted appearance of primary and secondary lamellae along with damage to gill epithelium under scanning electron microscopy at various magnifications. Mucosal cells of gills were found to secrete mucus showing primary reactions for membrane damage leading to dysfunction in respiration and osmoregulation.
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Spontaneously hypertensive rats were food deprived and trained to lever press on a fixed-ratio 10 schedule of food reinforcement in a paradigm in which responding was reinforced on one lever after an injection of clonidine (0.02 mg/kg) and on an alternate lever after an injection of saline. The spontaneously hypertensive rats learned the clonidine-saline discrimination to a criterion of correct lever selection on 10 consecutive days in an average of 39 training sessions. In subsequent tests, emission of clonidine discrimination responses was found to be both time dependent and dose dependent (ED50, 0.009 mg/kg). The antihypertensive drugs lofexidine (ED50, 0.03 mg/kg), guanabenz (ED50, 0.019 mg/kg), p-aminoclonidine (ED50, 0.23 mg/kg), methyldopa (ED50, 21.8 mg/kg), hydralazine (ED50, 0.98 mg/kg), prazosin (ED50, 0.72 mg/kg), minoxidil (ED50, 12.4 mg/kg) and pergolide (ED50, 0.021 mg/kg) were generalized to clonidine in a dose-dependent manner. Yohimbine antagonized both the antihypertensive action and the discriminative stimulus properties of clonidine in parallel without antagonizing those actions of hydralazine. Similarly, the discriminative stimulus properties and antihypertensive action of pergolide were antagonized by sulpiride in parallel without antagonizing any of those effects when produced by clonidine or hydralazine. Although the stimulus properties and response-suppressive actions of the antihypertensive or other drugs were not related, the ED50 values for generalization of the drugs to the clonidine stimulus and for their antihypertensive action were highly correlated (r = 0.99). These data suggest that clonidine produces an interoceptive discriminative stimulus that is based upon its antihypertensive action in spontaneously hypertensive rats.
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Rats were trained concurrently on sweetened-milk drinking and bar-press-responding behavior, which alternated on a daily basis. Dose-response functions for d-amphetamine were determined before and after conditions of chronic treatment. When given before chronic treatment, d-amphetamine decreased both milk consumption and reinforcement received for lever-pressing in a dose-dependent manner. Subsequently, three conditions of chronic injection were established in which one group received saline, prior to both tasks, another group received d-amphetamine prior to drinking milk and saline prior to lever-pressing and the third group received d-amphetamine prior to lever-pressing and saline before drinking milk. The rats became tolerant to d-amphetamine in the task in which the drug had been administered chronically; however, the same rats showed no tolerance in the other task in which saline had been administered chronically. Tolerance to d-amphetamine was thus shown to be behaviorally specific.
Rats were trained to discriminate the stimulus properties of cocaine using a two-lever choice paradigm, in which food reinforcement was delivered for responses on the correct lever: one lever was always correct after a 5 mg/kg injection of cocaine, and the other lever was always correct after an injection of saline. After training, administration of cocaine and methamphetamine were generalized to the cocaine lever in a dose-dependent fashion, but administration of phenylethylamine was only partially generalized. Training was then suspended, and cocaine (20 mg/kg) was injected every 8 hr. Tolerance developed progressively to the discriminative stimulus properties of cocaine. After six days of chronic administration, redetermination of dose-effect data showed the presence of tolerance and cross-tolerance to the stimulus properties of cocaine and methamphetamine, respectively, with no evidence for cross-tolerance to phenylethylamine. No tolerance or sensitization developed to the suppressant effects of cocaine on operant responding. After termination of the chronic administration of cocaine, the tolerance was lost at the same rate at which it was acquired. These data demonstrate that tolerance occurs to the stimulus properties of cocaine and suggests that a common mechanism mediates the stimulus properties of cocaine and methamphetamine.
Rats trained to discriminate pentylenetetrazol (PTZ) from saline in a two-lever food-reinforced operant task were given a three-day course of morphine, 15 to 45 mg/kg tid, ip. On the third day naloxone produced dose-dependent generalization to the PTZ stimulus, with 66% of subjects selecting the PTZ lever after the highest dose (0.32 mg/kg). Following termination of morphine injections, generalization of spontaneous withdrawal was tested. Approximately 50% of subjects selected the PTZ lever at 24 and 48 hrs after the last morphine, and by 96 hrs the percentage of subjects selecting the PTZ lever had dropped to 11%. Rats that chose the PTZ lever at 48 hrs were given diazepam, 5.0 mg/kg, which blocked the PTZ-like stimulus. These data demonstrate that morphine withdrawal produces a stimulus with PTZ-like characteristics which can be blocked by an anxiolytic, and they suggest that the PTZ discrimination may have general utility for investigating drug dependence and withdrawal in animals.
A biostatic assay method involving 45Ca uptake into shells and tissues of snails (Lymnaea vulgaris) in 72 hr was developed to follow the effect of detergent-polluted water on ecosystems. There was a marked decrease in the 45Ca uptake by shells and tissues of linear alkyl benzene sulfonate-exposed animals as compared to controls. No change in 45Ca uptake was observed in dead shells, thereby excluding the possibility of passive exchange.