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Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 1,279 records · Page 71Linked to original sources

Synthesis and biologic activity of a C-ring analogue of vitamin D3: biologic and protein binding properties of 11 alpha-hydroxyvitamin D3.

The influence of C-ring substituents on the biologic activity and protein binding properties of vitamin D3 has not been systematically investigated. To this end, we dehydrogenated cholesta-5,7-dien-3 beta-ol (1) to the 5,7,9(11)-triene. After protection of the 5,7-diene with a 4-phenyl-1,2,4- triazoline -3,5-dione Diels -Alder adduct, oxidation of the unprotected 9(11)-olefin gave epoxide 5. Reverse Diels -Alder and reductive ring opening of epoxide 5 gave cholesta-5,7-diene-3 beta, 11 alpha-diol (6). Photolysis of 6 to the previtamin followed by thermal rearrangement resulted in 11 alpha-hydroxyvitamin D3 (8). We found that vitamin 8 increased calcium transport at a dose of 500 pmol/rat but failed to increase bone calcium mobilization at a dose as high as 50 000 pmol/rat. Under the same conditions, corresponding doses of vitamin D3 and 25-hydroxyvitamin D3 increased bone calcium mobilization and intestinal calcium transport. The new vitamin analogue, 8, was slightly less efficient (B-50 = 6.8 X 10(-8) M) than 25-hydroxyvitamin D3, 24(R),25-dihydroxyvitamin D3, and 25-(S), 26-dihydroxyvitamin D3 (7.1 X 10(-9) M, 7.7 X 10(-9) M, and 7.9 X 10(-9) M, respectively) in displacing radiolabeled 25-hydroxyvitamin D3 from rat plasma vitamin D binding protein. On the other hand, vitamin analogue 8 showed significantly greater binding efficiency than 1 alpha-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, and vitamin D3 (B-50 = 2.5 X 10(-6) M, 9.84 X 10(-8) M, and 5.46 X 10(-7) M, respectively), under these same conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of nicotine and d-amphetamine on intracranial self-stimulation in a shuttle box test in rats.

Rats were permitted to turn on and off electrical stimulation of the medial forebrain bundle, by alternating between two photobeams running along opposite walls of a shuttle box. Entry into one beam (the "ON" beam) triggered the delivery of a succession of short, regularly occurring (1 Hz) pulse trains, which could be terminated by breaking the other ("OFF" beam). The two beams were frequently reversed. When this occurred, the rat was given a free period of 10 s in which to reorient, and brain stimulation reward was then assessed by the amount of time spent receiving brain stimulation (SST) within a fixed interval of time. SST increased with increasing current intensity. After training, subjects were tested for 10 consecutive days, alternately with saline and nicotine bitartrate (0.4 mg/kg SC base), and received a constant daily dose of the drug (0.4 mg/kg). Initially, nicotine visibly impaired motor performance for several minutes after injection, which may at least partly explain the observed reduction of SST; both effects waned across successive nicotine tests. Later in each 78 min session, nicotine consistently increased SST over a range of current, and drugged subjects entered the photobeams more frequently even when electrical stimulation was unavailable. d-Amphetamine sulphate (0.25, 0.75 mg/kg SC salt), given 15 min before testing, also increased SST and stimulated responding. The possible effects of motor impairment or activation on SST are discussed, and it is concluded that nicotine and d-amphetamine may have enhanced the rewarding properties of medial forebrain bundle stimulation.

Animals↗

Role of training dose in discrimination of nicotine and related compounds by rats.

Rats were trained to discriminate nicotine from saline in a two-bar operant conditioning procedure with food reinforcement. There was partial generalization to the nicotine analogues anabasine and cytisine in rats trained to discriminate either 0.2 or 0.4 mg/kg nicotine from saline. However, generalization was complete in rats trained to discriminate 0.1 mg/kg nicotine and, in a novel procedure, any one of three doses of nicotine (0.1, 0.2, or 0.4 mg/kg). There was no generalization to the muscarinic-cholinergic agonist oxotremorine (0.0025-0.04 mg/kg). Additional experiments were carried to further characterize the response of rats trained with nicotine (0.1 mg/kg). These animals failed to generalize to compounds from a range of pharmacological classes (i.e., apomorphine, cocaine, chlordiazepoxide, picrotoxin, and quipazine), but there was partial generalization to amphetamine. Mecamylamine (0.5 mg/kg) but not hexamethonium (5.0 mg/kg) blocked the discrimination of nicotine and the generalization to cytisine. Anabasine (1.0-4.0 mg/kg) did not block the response to nicotine. The results support the view that the nicotine cue is mediated mainly through central cholinergic mechanisms. The dose of nicotine used for training has a very significant influence on the characteristics of the cue and 0.1 mg/kg of nicotine may be more suitable than 0.4 mg/kg as a training dose in future work.

Alkaloids↗

Adult Wilms' tumor: clinical and radiographic features.

The clinical and radiographic features of Wilms' tumor in 4 adult patients are described. Wilms' tumors in adults are usually bulky and contain numerous areas of necrosis and hemorrhage, imparting a complex appearance to the lesion on sonography and computed tomography. Angiography reveals the tumor to be hypovascular with some neovascularity. No specific features of the lesion differentiate it from hypernephroma. In contrast to the childhood variety, Wilms' tumors in adults have ill-defined margins and frequently extend into the retroperitoneum. Their treatment is the subject of debate and prognosis is poor.

Adult↗

Development of a self-administered questionnaire to measure maternal adjustment and maternal attitudes during pregnancy and after delivery.

Having a baby entails very great changes in maternal intrapsychic and interpersonal adjustment, and childbearing is associated with an increased risk of psychiatric disorder. It may be possible, as pregnancy progresses, to find clues to such disturbances among the changes that occur in maternal attitudes and self-perceptions, This report describes the development and validation of a 60-item, self-administered questionnaire which aims to measure a mother's perceptions of her body, of somatic symptoms, the marital relationship, attitudes to sex and attitudes to the pregnancy and the baby. A pilot study of 99 women in late pregnancy was followed by repeated measures taken from 119 first-time mothers who were subjects in a longitudinal survey of mental health in a routine obstetric service setting. The questionnaire was acceptable to the mothers, it was reliable (test-retest and split-half) and comparisons with independently gathered interview data showed that it had criterion-related validity. The questionnaire is appended to this report (Appendix I).

Attitude↗

1,25-Dihydroxyvitamin D3 rapidly alters the morphology of the duodenal mucosa of rachitic chicks: evidence for novel effects of 1,25-dihydroxyvitamin D3.

When rachitic chicks are given 1,25-dihydroxyvitamin D3 in amounts as low as 50 ng/bird, the appearance of the duodenal mucosa is altered within 2 h of the administration of the hormone. The changes are most readily apparent on scanning electron microscopy and include: a more plump appearance of villi with loss of furrows and pits on their surfaces, elongation of villi and a smoother, more uniform microvillus surface. These changes occur within 2 h of the administration of the hormone and persist for as long as 24 h. The morphological change precedes the increase in calcium absorption induced by 1,25-dihydroxyvitamin D3 in the intestine. These observations suggest that 1,25-dihydroxyvitamin D3 may play an important part in maintenance of the structure of the duodenal mucosa.

Animals↗

Blood lead, behaviour and intelligence test performance in preschool children.

A variety of measures of behaviour and cognitive performance were taken on a group of preschool children together with a sample of venous blood. The relationship between blood lead and intelligence was small and statistically non-significant after controlling for other factors influencing cognitive performance.

Behavior↗

Secondary haemorrhage following tonsillectomy/adenoidectomy.

A series of 24 cases of secondary haemorrhage following tonsillectomy/adenoidectomy was investigated for bacterial causes of bleeding. Streptococcus pyogenes was isolated in one, streptococcus haemolyticus in another, the remainder being non-pathogens.

Adenoidectomy↗

Some effects of nicotine on food and water intake in undeprived rats.

Undeprived rats were tested in their home cages for intake of water and powered food, starting 15 min after subcutaneous (s.c.) injection of (-)-nicotine bitartrate or 0.9% w/v NaCl solution (saline). In the first 2 h, nicotine (0-0.4 mg kg-1 base) markedly reduced water intake in a dose-related way, leaving food intake unchanged. Food and water intake up to 24 h after injection was unaffected. Rats (n = 6 per group) were then injected daily with nicotine (0.4 mg kg-1 base, s.c.) or saline for one month. Intermittent tests with saline (in place of nicotine) during this period did not reveal any signs of abstinence. A dose-response study similar to the first was then carried out, and little or no tolerance was found to the hypodipsic action of nicotine. Nicotine also reduced food intake, irrespective of chronic treatment. Subsequently, daily injections were discontinued, and spontaneous intake did not differ in rats previously maintained on nicotine, relative to control animals. Mecamylamine (0.3, 1.5 mg kg-1, s.c.) prevented nicotine-induced hypodipsia, whereas chlorisondamine (0.02, 0.1 mg kg-1 s.c.) was ineffective. Both ganglion blockers reduced food intake. Nicotine did not reduce drinking in rats preloaded with a hypertonic saline solution. It is suggested that nicotine reduces water intake in undeprived rats, probably by acting centrally. Since this action changes little with repeated testing, it may provide a useful index of one or more central actions of the drug.

Animals↗

Reliability of clinical assessment of blunted affect.

The affect of 20 chronic schizophrenic in-patients was assessed by two psychiatrists using two rating scales. The interview recordings were reviewed three times--firstly with the auditory information only (the "audio review"), secondly with the visual information only (the "visual review") and thirdly with both (the "audio-visual review"). The "blunted affect score" correlated strongly with the total score of the verbal items of scales, but did not when a single mode of information was given. Since the absolute values of the "blunted affect score" were lower in the "visual review" than in the live interview and in the "audio-visual review", it was speculated that speech tended to bias the assessment of affect.

Adult↗

Metabolism of 1,25-dihydroxyvitamin D3.

Synthesis of 1,25(OH)2D3 is controlled by numerous factors. The major ones, however, are the circulating amounts of parathyroid hormone (the secretion of which is stimulated by low serum calcium), serum or extracellular fluid phosphorus concentrations, circulating levels of 1,25(OH)2D3 itself, and perhaps serum calcium directly. Many of the other factors noted have effects in vitro only or effects that are observed inconsistently or in one species only. Thus, in low-calcium states, 1,25(OH)2D3 synthesis increases because of increased parathyroid hormone activity. Parathyroid hormone may stimulate 1,25(OH)2D3 synthesis directly or via alterations (a decrease) in serum phosphorus or both. Low serum phosphorus will stimulate 1,25(OH)2D3 synthesis independent of parathyroid hormone levels. Low serum calcium may directly stimulate 25(OH)D3 1 alpha-hydroxylase activity independently of parathyroid hormone. In general terms the vitamin D-endocrine system tends to correct abnormalities in calcium and phosphorus homeostasis. The further metabolism of 1,25(OH)2D3 to other metabolites appears to be mainly a degradative or excretory process. Currently there is no evidence that 1,25(OH)2D3 must itself be altered to other metabolites prior to inducing intestinal calcium transport or bone mobilization. The processes involved in the excretion of 1,25(OH)2D3, such as side-chain oxidation and biliary excretion, are not regulated by serum calcium, phosphorus, or 1,25(OH)2D3 levels. The biliary excretion pathway is also unsaturable over a very wide range and not regulated by calcium, phosphorus, or vitamin D3. Therefore these processes, which account for a large part of the metabolism of 1,25(OH)2D3, are largely unregulated by factors that control the synthesis of 1,25(OH)2D3 and regulate the formation of other calcium-controlling hormones. Other processes involved in the metabolism of 1,25(OH)2D3, such as 24-hydroxylation and 26-hydroxylation, occur in normocalcemic and normophosphatemic states. 24-Hydroxylation is also induced by 1,25(OH)2D3, which benefits the organism, because excessive 1,25(OH)2D3 in various tissues can be altered to a less active metabolite, 1,24,25(OH)3D3. Although there is still no evidence concerning the regulation of C-24 oxidation by dietary calcium and phosphorus levels, the fact that this process is induced by 1,25(OH)2D3 suggests that the metabolic pathway functions in much the same manner as the 24-hydroxylation pathway. The formation of 1,25(OH)2D3-26,23-lactone occurs in normocalcemic states and in situations in which 1,25(OH)2D3 has been administered.

Animals↗

Protein phosphotransferases from liver of ageing rats.

Cyclic AMP-dependent and -independent protein kinase have been isolated from livers of rats at 3, 9, 18 and 30 months of age. A preliminary characterization reported here reveals that in addition to a decrease in their activities due to ageing and a likely shift to cyclic AMP-independent casein kinase activity at 30 months of age, the enzymes show modest changes in some of their kinetic properties. In the case of cyclic AMP-dependent enzymes, decreases in Vmax for ATP and Km for cyclic AMP as well as histones were observed. On the contrary, casein kinases displayed increases in Km values for casein, GTP and ATP. Molecular weights of 143,000 daltons for casein kinases from 3-, 9- and 18-month-old rats and 211,000 daltons for that from 30-month-old rats were obtained. Slight differences were also noticed in the inhibitor sensitivity (NaF and 2,3-diphosphoglyceric acid) of casein kinases isolated from rats of different ages.

2,3-Diphosphoglycerate↗

Controlled study on time reproduction of depressive patients.

23 depressive inpatients and the same number of matched nonpsychiatric controls were examined three times: following admission, and 14 and 28 days thereafter. Hamilton's Rating Scale for Depression and the Time Reproduction Test were administered. Time reproduction was found not to be different between patients and normal controls and within patients. Nor was a significant correlation found with any clinical symptoms.

Adult↗