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V M Kumar

Publications and source records attributed to V M Kumar.

At least 19 recordsLinked to original sources

Tonic activity of alpha1 adrenergic receptors of the medial preoptic area contributes towards increased sleep in rats.

Several studies have suggested that noradrenergic afferents to the medial preoptic area might be involved in hypnogenesis and in lowering the body temperature, and that the alpha1 adrenergic receptors might be mediating these responses. This study was undertaken to find out the changes in sleep-wakefulness and body temperature in rats, when these adrenergic receptors of the medial preoptic area are blocked by alpha1 selective antagonist, prazosin. Adult male Wistar rats were chronically implanted with electrooculogram, electroencephalogram and electromyogram electrodes for sleep-wakefulness assessment, and a bilateral guide cannula for microinjection of prazosin at the medial preoptic area. A radio-transmitter was implanted in the abdomen for telemetric measurement of body temperature in four groups of rats. Sleep-wakefulness was also assessed telemetrically in four other groups of rats. Sleep-wakefulness recordings from these rats were done in a specialized chamber, where they could move about freely and select the ambient temperature which they prefer. Prazosin induced a dose dependent increase in wake period and in body temperature, when microinjected into the medial preoptic area. Results suggest that preoptic alpha1 adrenergic receptors mediate hypnogenic and hypothermic responses. It is proposed that the noradrenergic afferents to the medial preoptic area, by tonic activation of alpha1 adrenergic receptors, contribute towards increase in sleep especially during the daytime.

Adrenergic alpha-Antagonists↗

Differences in the effects of medial and lateral preoptic lesions on thermoregulation and sleep in rats.

The effects of the destruction of the medial preoptic area and the lateral preoptic area with N-methyl-d-aspartic acid on sleep-wakefulness, brain temperature and thermoregulation were studied in two groups of male Wistar rats. Electroencephalogram, electrooculogram and electromyogram, along with brain temperature, were recorded for 3 days, prior to the destruction of the medial preoptic area and the lateral preoptic area, and on the 7th and 21st days after the destruction of these areas. The thermoregulatory capacity of the rats was assessed by recording their brain temperature when they were exposed to severe cold (5+/-1 degrees C) and heat (37+/-1 degrees C) before and after the lesion. Though sleep was decreased after the destruction of both the medial preoptic area and the lateral preoptic area, paradoxical sleep was reduced only by the destruction of the medial preoptic area. Decrease in sleep after the medial preoptic area lesion was brought about by a decrease in the duration of the slow wave sleep episodes and the frequency of paradoxical sleep episodes. Decrease in sleep after the lateral preoptic area lesion was brought about by a decrease in the frequency of slow wave sleep episodes. There was a significant increase in brain temperature after the medial preoptic area lesion but not after the lateral preoptic area lesion. The rats with lesion in the medial preoptic area showed deficits in thermoregulation on exposure to cold, while those with the lateral preoptic area lesion showed deficits in heat defense ability. The present findings suggest that the medial preoptic area and the lateral preoptic area regulate sleep by different modalities and that there is an anatomical segregation of heat and cold defense functions within the basal forebrain.

Animals↗

Atenolol or butoxamine injection at the lateral septum doesn't inhibit male sexual behavior in rats.

To investigate the role of specific adrenoreceptors subtypes on sexual behavior, atenolol, butoxamine, a mixture of atenolol and butoxamine, and saline (vehicle) were injected into the lateral septum in four different groups of sexually active male rats. Application of a mixture of atenolol and butoxamine produced inhibition of copulatory activity. On the other hand, application of either atenolol or butoxamine alone did not inhibit copulatory activity. But it produced stimulation of some of the components of male sexual behavior. Inability of either atenolol or butoxamine to inhibit the male sexual behavior, and inhibition of the same by the mixture of atenolol and butoxamine, indicate that both beta-adrenoreceptors at the lateral septum are involved in the elaboration of male sexual behavior. Stimulation of some components of sexual behavior on application of atenolol or butoxamine could be attributed to an unbalanced activity of beta-adrenoreceptors.

Animals↗

Orexin A (hypocretin-1) application at the medial preoptic area potentiates male sexual behavior in rats.

The medial preoptic area plays an important role in the regulation of male sexual behavior in rats, and this area receives orexinergic inputs. The role of orexinergic inputs in the medial preoptic area in sexual behavior has not been studied, though they have been shown to play a role in some other physiological functions. In this study, the changes in male sexual behavior in rats were studied after local injection of orexin A (Hypocretin-1) at the medial preoptic area. The results of the study showed that orexin A application at the medial preoptic area increased sexual arousal as well as the copulatory performance. Sexual arousal is one of the physiological stimuli, which influences wakefulness. It is possible that the earlier reports showing increased wakefulness, on application of orexin A at the medial preoptic area/basal forebrain, has a contribution from sexual arousal.

Animals↗

Role of the medial preoptic area in thermal preference of rats.

This study was conducted to find out whether the medial preoptic area (mPOA) plays a role in the selection of ambient temperature by rats. Adult male Wistar rats were kept in an environmental chamber having three interconnected compartments, maintained at three different temperatures (18 degrees, 24 degrees and 30 degrees C) in which the animals could move freely from one compartment to the other. Normal rats preferred to stay at the chamber maintained at 24 degrees C for most of the time, during day and night. The temperature preference shifted to 30 degrees C after the mPOA of these rats had been lesioned by local administration of 5 micrograms of N-methyl D-aspartic acid (NMDA) in 0.2 microliter distilled water. The results of the study suggest that the mPOA acts as a fine tuning center for homeostatic regulation of thermal balance, including selection of appropriate thermal environment. It is proposed that after the mPOA lesion, the animal cannot assess properly the energy status of the body and thereby prefers a higher ambient temperature.

Animals↗

Micropropagation of Paulownia fortuneii through in vitro axillary shoot proliferation.

Primary cultures were established with nodal segments from juvenile shoots of two- year-old Paulownia fortuneii trees from a clonal plantation in Andhra Pradesh. A medium containing half-strength MS salts + RAP (1 mg/L) + sucrose (2%) produced optimum bud break in nodal explants. The same basal medium with reduced hormone level (0.5 mg/L) supported maximum multiplication of secondary cultures of P. fortuneii (1:6 in 6 weeks). Specific treatments were tested to enhance this rate of multiplication. In one approach, five to six week old in vitro grown shoots were ratooned (cutting the main shoot at the bottom leaving one node). The stumps (ratooned basal node) produced 2 to 3 axillary shoots, which grew into 4 to 5 nodes by 3 weeks; thus, providing additional shoots from the same explant. This provided 30% additional shoots in 4 cycles. Secondly, reducing the light intensity to 1200 lux resulted in higher shoot elongation, i.e, formation of 8 nodes in 5 weeks with healthier shoots than the normal intensity of 3000 lux under which only 6 nodes were produced in 6 weeks. In vitro-grown shoots could be successfully rooted ex vitro in vermiculite + cocopeat mixture (1:1 v/v) under 90% humidity, transferred to soil in polybags for hardening in the green house for 2 weeks and shifted to shade net for further hardening. After one month, the plants could be successfully transplanted to field with 95% survival. Micropropagated plants showed an excellent growth in the field attaining a height of 1.5 m and a collar diameter of 2.8 cm in 3 months.

Lamiaceae↗

Effect of ambient temperature on sleep-wakefulness in normal and medial preoptic area lesioned rats.

The changes in sleep-wakefulness were studied in rats during their exposure to different ambient temperatures of 18 degrees C, 24 degrees C and 30 degrees C, before and after the destruction of the medial preoptic area neurons by N-Methyl D-aspartic acid. In normal rats, there was an increase in paradoxical sleep and slow wave sleep and a decrease in wakefulness at higher ambient temperatures. The increase in sleep was primarily due to an increase in the duration of sleep episodes. Destruction of the medial preoptic area neurons produced a decrease in sleep at all three different ambient temperatures. But, there was a linear increase in sleep with higher temperatures in the lesioned rats that was qualitatively different from that in the normal animals, as the increase in sleep was associated with an increase in the number of short duration slow wave sleep episodes. The findings indicate that the medial preoptic area is essential for sleep maintenance and improving the quality of sleep with higher ambient temperatures. It is possible that the medial preoptic area serves as a fine-tuning mechanism to regulate sleep for energy homeostasis, including thermoregulation.

Analysis of Variance↗

Effects of long-term treatment with testosterone enanthate in rhesus monkeys: I. Pharmacokinetics of testosterone, testicular volume and liver metabolism of testosterone.

The effects of long-term administration of testosterone enanthate on the pharmacokinetics and bioavailability of testosterone were studied in adult male rhesus monkeys (n = 9), injected with 50 mg of testosterone enanthate (TE) once every 14 days for a total of 32 months. Control animals were injected with 0.2 mL olive oil. Serum testosterone levels increased sharply within 24 h of the first injection of TE and reached a peak on day 3 followed by a sharp decline, but baseline values were not reached even by day 14. Subsequent injections of TE caused a similar pharmacokinetic profile until the 55th injection; testosterone levels on day 3 declined from the 56 to 58th injection and remained in a lower range until the last injection. Repeated injections of TE increased the bioavailability of testosterone as shown by the Area Under the Curve. The nocturnal (22.00 h) surge in testosterone levels during the pretreatment phase was abolished by TE injections. TE injections altered the metabolism of testosterone by the liver, as studied in vitro; while liver from control animals converted testosterone to androstenedione as the major metabolite, androsterone was the major metabolite in chronically TE-treated animals. Spermatogenesis and the associated increase in testicular volume observed in control animals in winter were suppressed in TE-treated animals. The results indicate that repeated TE injections elevate serum testosterone to supra-physiological levels with marked fluctuations in circulating testosterone levels after each injection. Possibly in response to these elevated levels, there was a change in the metabolism of testosterone by the liver as observed in vitro.

Animals↗

Neural regulation of glucose homeostasis.

The regulation of blood glucose is generally stated to be under the control of the endocrine system. But the endocrine secretion is itself regulated by the central nervous system, especially the hypothalamus. The brain can sense the energy status of the body by using neural afferent signals and metabolic cues such as glucose. A variety of experimental evidences have been put forth to support the postulate that there are "glucoreceptors", sensitive to blood glucose and glucose utilization, in the hypothalamus. Gastrointestinal afferents, which carry information about the energy intake, reach the hypothalamic regions and interact with the glucose sensitive mechanisms. Available evidence suggests that obesity and decreased body weight, resulting from lesions of the hypothalamic 'satiety' and 'feeding' centres respectively, are not only due to altered food intake, but also to derangement in glucose homeostasis. The medial preoptic area does the fine tuning of energy balance (regulation of food intake) in response to alterations in the temperature, locomotor activity and sleep wakefulness. Thus the hypothalamus regulates energy balance through its control of energy intake on the one hand, and its expenditure and storage on the other. Neuroendocrine system and autonomic nervous system deal with storage and expenditure of energy.

Animals↗

Alterations in monoamine neurotransmitters and dendritic spine densities at the medial preoptic area after sleep deprivation.

The experiments were conducted on 24 adult male Wistar rats to find out the alterations in the levels of monoamines and dendritic spine densities in the medial preoptic area and cortex after total sleep deprivation. Noradrenaline was reduced in the medial preoptic area, though there was no significant change in the cortex. Dopamine and serotonin were decreased both in the medial preoptic area and in the cortex. Dendritic spine counts in the medial preoptic area and the motor cortex were increased after total sleep deprivation. Enhanced release of the monoamines and their subsequent breakdown during sleep deprivation could be responsible for the decreased levels of the transmitters. An increase in synaptic activity, resulting in the enhanced release of the transmitters, might be responsible for the increased spine density after total sleep deprivation. Localized changes in noradrenaline levels at the medial preoptic area suggest its involvement in sleep genesis and maintenance, though its possible contribution to other functions like thermoregulation and reproduction cannot be ruled out. As the available literature does not indicate a role for serotonin and dopamine at the medial preoptic area in sleep regulation, these changes may represent their participation in non-sleep functions.

3,4-Dihydroxyphenylacetic Acid↗

Effect of NMDA lesion of the medial preoptic neurons on sleep and other functions.

This study was undertaken to determine the effects of the destruction of the medial preoptic area (mPOA) neurons by N-methyl D-aspartic acid (NMDA), on sleep-wakefulness (S-W), locomotor activity, body weight, rectal temperature, and food and water intake in rats. The NMDA lesion of the mPOA produced long-lasting insomnia with marked reduction in the deeper stages of sleep, including paradoxical sleep. The reduction in the duration of sleep episodes in the lesioned rats indicated their inability to maintain sleep. The insomnia resulting from a decreased sleep pressure did not alter the sleep-initiating ability. Though the day-night distribution of sleep remained largely unaffected, there was an increase in locomotor activity during the light period. There was no increase in food intake to compensate for the high energy expenditure resulting not only from hyperactivity but also from hyperthermia in the mPOA-lesioned rats. Thus, body weights of the rats were reduced even without any change in food and water intake. However, the changes in body temperature and locomotor activity after the mPOA neuronal loss may not have exerted a major influence on S-W, as the alterations in all these parameters had different time courses.

Animals↗

Recovery of sleep after fetal preoptic transplantation in medial preoptic area-lesioned rats.

Changes in sleep after fetal preoptic (POA) tissue transplantation were studied in rats which had been made insomniac by a medial preoptic area (mPOA) lesion. Two days after the N-methyl D-aspartic acid (NMDA) lesion of the mPOA, fetal POA tissues (obtained from 14- to 17-day-old fetuses) were transplanted into the lesioned mPOA. Insomnia was less marked in these animals, as compared to nontransplanted lesioned rats, even on the 4th day after transplantation. The quantum of sleep nearly attained the prelesion level by the 20th day. Body weight also showed recovery after transplantation. Rectal temperature, which was increased by the lesion of the mPOA, remained unaltered even after the transplantation. These results suggest that the recovery of sleep and rectal temperature may follow different time courses. Surviving transplanted neurons were seen at the site of lesion on postmortem examination. Humoral interaction between the host and the transplant may be responsible for the early recovery of sleep, though the establishment of neural connections between the host and transplant might have contributed to the later recovery. This is the first study to show the recovery of sleep function in insomniac animals after fetal preoptic tissue transplantation. However, the specificity of the POA fetal tissue, in comparison with other neural tissues to promote sleep recovery, remains to be established.

Animals↗

The role of alpha-2 receptors in the medial preoptic area in the regulation of sleep-wakefulness and body temperature.

The study was conducted on 48 free-moving male rats to find out the role of the medial preoptic alpha2 receptors in the regulation of sleep and body temperature. Recording electrodes for assessment of sleep-wakefulness, and injector cannulae for injection of drugs in the medial preoptic area were chronically fixed on the skulls of the animals. The noradrenergic fibres projecting to the medial preoptic area were destroyed in 24 rats by administration of 6-hydroxydopamine at the ventral noradrenergic bundle. Though arousal was produced in normal rats by the injection of the alpha2 adrenergic agonist, clonidine, at the medial preoptic area, it induced sedation in rats with noradrenergic fibre lesion. Clonidine did not alter the rectal temperature in normal rats but it induced hypothermia in lesioned rats. Injection of alpha2 antagonist, yohimbine, at the medial preoptic area induced sleep in rats with intact noradrenergic fibres. However, the sleep inducing effect of this drug was very much attenuated in the lesioned animals. There was no significant change in body temperature, in both these groups of animals, after yohimbine administration. The study indicates the role of presynaptic alpha2 adrenergic receptors in arousal response and indirectly supports the contention that the alpha1 postsynaptic receptors at the medial preoptic area are involved in hypnogenesis. It also suggests that the thermal changes induced by adrenergic system are mediated through alpha1 postsynaptic receptors. But the thermal changes do not contribute towards the induced alterations in sleep-wakefulness. It is proposed that there should be separate sets of noradrenergic terminals for regulation of sleep and body temperature.

Administration, Topical↗

Changes in magnetic resonance imaging and sex behavior after 6-OHDA injection in the medial preoptic area.

Magnetic resonance imaging (MRI) of the brains of male rats was done before and after destroying the catecholamine (CA) fibers by local application of 6-hydroxydopamine (6-OHDA) in the medial preoptic area (mPOA). The male sexual behavior was also assessed before and after injection of this toxic drug. The administration of 6-OHDA (8 microg) resulted in highly variable lesions, as shown by MRI and confirmed by histological examination. A hyperintense area was visible either on one or on both sides, about 1-3 h after the administration of the drug. Postmortem histofluorescence showed destruction of CA fibers in the mPOA on those sides that showed hyperintense areas in the MRI. No CA fiber destruction was seen in those rats that had shown no change in MRI after 6-OHDA injection. There was a transient reduction in sex drive score in all the 6-OHDA-treated rats. The present findings point out a correlation between the MRI changes and CA fiber destruction, whereas the transient reduction in the sexual behavior was not related to these changes. It is suggested that some biochemical events related to 6-OHDA destruction of CA fibers may have been responsible for the hyperintensity seen in the MRI.

Animals↗

Toxic effect of systemic administration of low doses of the plasticizer di-(2-ethyl hexyl) phthalate [DEHP] in rats.

DEHP [di-(2 ethyl hexyl) phthalate], a widely used plasticizer in blood storage bags, leaches out in appreciable amounts into blood (about 10 mg/100 ml) resulting in exposure of recipients of blood transfusion to this compound. Various reports indicate the toxicity of DEHP, particularly in liver and reproductive organs but all these studies used large doses (up to 2 g or more/Kg body weight) and oral route of administration which are not relevant to the intravenous administration during blood transfusion or the low amounts present in blood. We have studied changes in the activity of some important enzymes-gamma-GT, ALT, CPK, LDH, alkaline phosphatase, acid phosphatase, beta-glucuronidase and few other parameters like vitamin E, glutathione, serum albumin etc in rats administered low doses of DEHP (corresponding to transfusion of 2, 4, 6 and 10 units of blood). Histopathology of the organs has also been carried out. The results obtained indicate no serious toxic effects for DEHP at the level present in blood stored in DEHP plasticized blood bags as evidenced by the lack of any significant alteration in most of the biochemical parameters studied. Even in those cases where there was alteration (for e.g., decrease in the level of vitamin E) 24 hr after administration of DEHP, it returned to near normal level with in 72 hr to 7 days. No histopathological changes were observed in any of the organs at these levels of DEHP. It is concluded that DEHP did not cause any serious toxic effect even at doses corresponding to transfusion of several units of blood in a recipient.

Animals↗

Stroke recurrence in diabetics. Does control of blood glucose reduce risk?

BACKGROUND AND PURPOSE: Patients with diabetes are at increased risk of stroke. Risk might be reduced if blood glucose level were controlled. METHODS: In a population-based study, we enrolled 621 patients within a month of an initial ischemic stroke and followed them regularly twice annually; 198 were diabetic. We monitored blood glucose level in 142 (72%) using glycosylated hemoglobin (HbAlc). Recurrent stroke frequency was determined by history, examination, and medical records. Cox proportional hazards models were used to examine the relationship between risk of recurrent stroke and HbAlc level. The models included interaction with time-dependent HbAlc level and history of diabetes, selected medical comorbidities, age, and sex. HbAlc level was analyzed as both a continuous and a dichotomous variable (ie, controlled versus uncontrolled); "controlled" was defined with different cut points. RESULTS: All but 17 patients (12%) whose blood glucose was monitored were well controlled (HbAlc < 8%). HbAlc level was not associated with increased risk of stroke recurrence (hazard ratio [HR], 0.87 per 1% increment in HbAlc; 95% confidence interval [CI], 0.623 to 1.219), nor was there a trend toward increased risk of recurrent stroke as the cut point defining "controlled" increased: with HbAlc at < 6%, the HR for the uncontrolled group was 0.51 (95% CI, 0.176 to 1.503); at < 7%, it was 0.43 (95% CI, 0.089 to 1.923); and at < 8%, it was also 0.43 (95% CI, 0.057 to 3.317). CONCLUSIONS: Among diabetic patients with an initial stroke, no association between HbAlc level over time and risk of stroke recurrence was found. However, most patients in this cohort were well controlled, and any adverse effect of poor control could not be adequately tested.

Aged↗

Male sexual behaviour not abolished after medial preoptic lesion in adult rats.

N-methyl-D-aspartic acid (NMDA) was injected into the medial preoptic area (mPOA) of 10 rats to destroy the neurones in this region. Male sexual behaviour was scored before, and on days 2, 6, 10, 17, 24 and 31 after the administration of NMDA. The neurones in the injection site were destroyed in all the rats, but male sexual behaviour was only transiently reduced in the animals with lesions largely restricted to the mPOA. These findings are in contrast to the earlier reports of permanent suppression of sexual behaviour after electrolytic lesion, with damage to the neurones and fibres of passage. The present study shows that the mating behaviour could be expressed even after the destruction of the neurones in the mPOA.

Animals↗

beta-adrenergic modulation of male sexual behavior elicited from the medial preoptic area in rats.

This study was aimed at investigating the role of the adrenergic mechanism in the medial preoptic area (mPOA) in sexual arousal and copulatory performance. Saline, norepinephrine (NE), phenoxybenzamine (PBZ) and propranolol (PROP) were injected into the mPOA in different groups of rats. NE application (3 micrograms) facilitated the male sexual behavior by increasing sexual arousal and copulatory performance. On the other hand, application of PROP and PBZ produced inhibition of male sexual behavior. Effects produced by low doses of PROP were more significant than PBZ. The results, viewed in the light of other available reports, suggest that the mPOA beta-adrenergic mechanism is important in the elaboration of male sexual behavior.

Adrenergic alpha-Agonists↗