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Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 1,261 records · Page 70Linked to original sources

Synthesis and biological activity of 3 beta-fluorovitamin D3: comparison of the biological activity of 3 beta-fluorovitamin D3 and 3-deoxyvitamin D3.

The alteration in the biologic activity of the vitamin D3 molecule resulting from the replacement of a hydrogen atom with a fluorine atom is a subject of fundamental interest. To investigate this problem we synthesized 3 beta-fluorovitamin D3 6 and its hydrogen analog, 3-deoxyvitamin D3 7, and tested the biologic activity of each by in vitro and in vivo methods. Contrary to previous reports which showed that 3 beta-fluorovitamin D3 was as active as vitamin D3 in vivo, we found that the fluoro-analog was less active than vitamin D3. With regard to stimulation of intestinal calcium transport and bone calcium mobilization in the D-deficient hypocalcemic rat, 3 beta-fluorovitamin D3 showed significantly greater biologic activity than its hydrogen analog, 3-deoxyvitamin D3. In the organ-cultured, embryonic chick duodenum, 3 beta-fluorovitamin D3 was approx 1/1000th as active as the native hormone, 1,25-dihydroxyvitamin D3, while 3-deoxyvitamin D3 was inactive even at microM concentrations, in the induction of the vitamin D-dependent, calcium-binding protein. With regard to in vitro activity in displacing radiolabeled 25-hydroxyvitamin D3 from vitamin D binding protein and radiolabelled 1,25-dihydroxyvitamin D3 from a chick intestinal cytosol receptor, 3 beta-fluorovitamin D3 and 3 beta-deoxyvitamin D3 both showed very poor binding efficiencies when compared with vitamin D3. Our results show that the substitution of a fluorine atom for a hydrogen atom at the C-3 position of the vitamin D3 molecule results in a fluorovitamin 6 with significantly more biological activity than its hydrogen analog, 3-deoxyvitamin D3 7.

Animals↗

Synthesis and biologic activity of 3 beta-thiovitamin D3.

We synthesized 3 beta-thiovitamin D3 from 7-dehydrocholesterol and tested its biological activity and protein binding properties. The thiovitamin was found to be a weak vitamin D agonist at high doses in vivo. It was poorly bound by both vitamin D-binding protein as well as by the intestinal cytosol receptor for 1,25-dihydroxyvitamin D. It did not increase the synthesis of calcium binding protein in the chick embryonic duodenum and did not block the activity of 1,25-dihydroxyvitamin D3 in this system. We conclude that 3 beta-thiovitamin D3 is a weak vitamin D agonist in vivo with no agonist activity or antagonist activity to 1,25-dihydroxyvitamin D3 in the chick embryonic duodenum.

Animals↗

Production of prostacyclin by different cell types of the goat ovary.

A sensitive platelet aggregation-inhibition assay was used to quantitate the production of prostacyclin by different cell types of the goat ovary. The assay could detect as low as 0.16 ng in the test sample. Different cell types i.e. granulosa, theca and corpus luteum or the total ovarian homogenate were incubated at 37 degrees C for 10 minutes with or without 0.2mM arachidonic acid. Rat aortic strips were incubated under similar conditions as a positive control. Under basal conditions the amount of prostacyclin produced by corpus luteum cells was higher compared to that by granulosa cells. When the precursor of prostaglandins (arachidonic acid) was provided the production markedly increased in corpus luteum, granulosa, and ovarian homogenate as well as in aortic strips. Theca cells did not produce detectable levels of prostacyclin even when the precursor was provided. Trapidil did not alter the basal but enhanced the arachidonic acid-stimulated prostacyclin production in homogenate and granulosa cells with no further increase in corpus luteum cells. U-51605 decreased basal as well as arachidonic acid-stimulated prostacyclin production in all the cell types. The prostacyclin production in ovaries is compartmentalized suggesting a possible role in ovarian physiology.

Animals↗

The physiology and pathophysiology of vitamin D.

The vitamin D endocrine system plays an important role in the maintenance of normal calcium homeostasis. Abnormalities of this system occur in many conditions, such as rickets, osteomalacia, hypoparathyroidism, and hyperparathyroidism. The diagnosis and treatment of these disorders will be facilitated if the clinician understands the general mechanisms by which defects in vitamin D metabolism and action occur. We review this information and discuss the use and limitations of vitamin D metabolite assays for diagnosis of clinical disorders of mineral metabolism.

Calcifediol↗

A study of serum ferritin in beta thalassemia. Iron deficiency and overload.

Serum ferritin, serum iron, and unsaturated iron binding capacity were studied in 64 patients with beta homozygous thalassemia (BHT), 120 patients with beta heterozygous thalassemia, and 46 normal subjects. Incidence of iron overload seen in 32 BHT cases was similar in untransfused and transfused cases. Among heterozygotes, iron stores were depleted in 24 (20%), mostly females (70.8%). Only male heterozygotes but not normals were iron deficient. In 18 (75%) heterozygotes with depleted iron stores, transferrin saturation (TS) was normal. It was also normal in 8 (25%) BHT patients and 5 (100%) heterozygotes with iron overload. In 13 (35.1%) BHT patients, it was raised in the absence of iron overload. It was concluded that iron deficiency in heterozygotes is of greater magnitude, especially in females, than hitherto known in India. Transferrin saturation is not a good indicator of either iron depletion or overload. Iron supplementation is recommended in heterozygous beta thalassemia in infants, children, and expectant mothers in geographic areas with high incidence of iron deficiency.

Child↗

Vitamin B12, folate, and iron studies in homozygous beta thalassemia.

The efficacy of serum folate (SF), red blood cell folate (RCF), and serum B12 in diagnosing folate and B12 deficiency, and the effect of iron overload on hemoglobin, were studied in 157 cases of homozygous beta thalassemia (HBT). The patients had lower SF compared with normal subjects (NS) (P less than 0.001) and higher RCF than their parents (P less than 0.001) and NS (P less than 0.001). Forty percent of patients had both low SF (less than 3 ng/mL) and high RCF (greater than 600 ng/mL). Homozygous beta thalassemia patients are known to have folate deficiency. Yet, both folate and B12 deficiency status were similar in the authors' patients and NS. These deficiencies apparently were less in patients compared with their parents, who shared the same nutritional milieu (P less than 0.001). Mean hemoglobin in patients with iron overload (transferrin saturation, TS greater than 50%) was lower than in those without (P less than 0.005). The following is concluded: (1) diagnosis of folate and B12 deficiency based on SF, RCF and serum B12 is vitiated in HBT and needs a therapeutic trial; (2) iron overload of a magnitude indicated by TS greater than 50% can aggravate anemia in HBT.

Blood Transfusion↗

Clear cell chondrosarcoma.

The clinical, radiologic, and histopathologic features of three cases of clear cell chondrosarcoma are described. On radiographs, this rather benign-appearing tumor resembles a chondroblastoma when it occurs at the end of a long bone, and may occasionally show a calcified matrix. However, it has distinctive tumor cells with a centrally placed vesicular nucleus surrounded by clear cytoplasm. The lesion has a low-grade malignancy and is amenable to en bloc surgical resection, which results in a much better prognosis than that of conventional chondrosarcoma.

Adult↗

Puerperal mental illness, clinical features and classification: a study of 142 mother-and-baby admissions.

The case notes were studied of 142 mothers admitted to psychiatric hospitals in the south-east Thames region within 12 months of childbirth during the years 1979 and 1980. Only 6% of the sample were categorised as schizophrenics by RDC criteria, whereas affective disorders were found to predominate in 80%. Manic and schizo-affective illnesses almost always began within two weeks of parturition, as did psychotic depressions. A third of the patient sample had suffered relatively minor disorders, and given adequate resources, some might have been better managed in the community. A parallel investigation of diagnostic returns to the Department of Health revealed considerable uncertainty about how to classify puerperal mental illnesses in accordance with ICD-9. There is an urgent need to improve the system for categorising and registering mental illnesses related to childbirth. Until this is achieved, research into aetiology, outcome, and the provision of services will continue to be impeded.

Anxiety Disorders↗

Biologic activity of 3beta-D-glucopyranosides of vitamin D compounds.

Polar glycosidic conjugates of vitamin D compounds occur in the vegetable and possibly in the animal kingdom. The biologic activity of these conjugates has not been examined systematically. To obtain more information on the biological role of such sterol conjugates, we examined the biological activity of the 3beta-D-glucopyranosyl conjugates of vitamin D3 5, 25-hydroxyvitamin D3 6, 1alpha-hydroxyvitamin D3 7 and 1alpha,25-dihydroxyvitamin D3 8. When these compounds were administered i.v. we found that a dose of between 50 and 500 pmol/rat of the four glucopyranosides tested increased active intestinal calcium transport and increased bone calcium mobilization in vitamin D-deficient rats fed a low calcium diet. Under the same conditions, corresponding doses of the parent vitamin D3 compounds elicited comparable increases in both intestinal calcium transport and bone calcium mobilization. When these compounds were administered p.o. 3beta-D-glucopyranosyl vitamin D3 5 exhibited no biological activity at doses of up to 5000 pmole/rat, whereas the corresponding glycosides of 25-hydroxyvitamin D3 6, 1alpha-hydroxyvitamin D3 7 and 1,25-dihydroxyvitamin D3 8 were active at doses of 500 to 1000 pmol/rat in the intestinal calcium transport system. When the glucopyranosyl conjugates were administered i.v. to vitamin D-deficient rats, 25-hydroxyvitamin D3 and 1alpha,-25-dihydroxyvitamin D3 were detected in the serum at levels less than or equal to those noted in animals dosed with the respective free sterols.

Animals↗

Mast cells in histoid lepromatous lesions.

Ten patients with histoid lesions among the lepromatous leprosy cases, of both sexes in the age group of 35-65 years, were included in this study. Skin biopsy from the nodule with surrounding healthy skin of histoid lesion was taken. The biopsies were fixed in Susa solution and processed for light microscopy. 5-7 mu thick sections were cut and stained with haematoxylin and eosin, Toluidine blue and Fite Faraco. Observations were made on the dermis to locate the mast cells and bacilli. Proliferation of mast cells and their degranulation were seen in the histoid nodule as compared to surrounding normal healthy skin where the cells were mainly intact. The study further investigates the role of mast cells in the histopathogenesis of the disease.

Adult↗

Efficacy of three mycobacterial antigens in the serodiagnosis of tuberculosis.

Three different antigens were tested for detection of mycobacterial antibodies. The 3 antigens were mycobacterial saline extract (MSE), mycobacterial sonicate (MSO) and PPD. For detection, both the soluble antigen fluorescent antibody (SAFA) and the enzyme-linked immunosorbent assay (ELISA) tests were used. We used 88 serum samples (50 from clinically, radiologically and/or bacteriologically proven cases of tuberculosis, 8 from proven cases of leprosy and 30 from healthy controls). With MSE antigen, both the tests were found to be highly sensitive and specific. MSO antigen was found to give better results in ELISA than in SAFA. The sensitivity and specificity of ELISA as well as SAFA test was reduced when PPD was used as an antigen. However, both ELISA and SAFA tests revealed that the mean antibody level in the patients with active tuberculosis was significantly higher than that in the healthy controls, irrespective of the antigen used.

Antibodies, Bacterial↗

Anterograde amnesia with oral lorazepam.

Twelve healthy volunteers were enrolled in a double-blind placebo-controlled study to evaluate the amnestic effects of orally administered lorazepam. The subjects were tested for immediate and delayed recall, using a word recall memory task. The subjects taking lorazepam did not differ from subjects receiving placebo on immediate recall. However, the delayed recall scores of lorazepam subjects were significantly lower compared to the placebo group (p less than .01).

Administration, Oral↗