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Biomedical subjects

R Rajan

Publications and source records attributed to R Rajan.

At least 91 records · Page 5Linked to original sources
PubMed1984

Effects of catechol estrogen methyl ethers on lipid metabolism in prepubertal rats.

Thirty-five day old ovariectomised rats were given daily subcutaneous injections (0.05-5.0 micrograms/100 gm body weight) of estradiol (E2) 2-methoxyestradiol (2-ME2) or 4-methoxyestradiol (4-ME2) for six days. At the end of the last injection, the animals were sacrificed and serum lipoproteins were analysed. It was observed that cholesterol decreased significantly in normal fed animals who received E2 and 4-ME2, while no effect was seen in cholesterol fed animals. In the E2 treated group there was a decrease in esterified and free cholesterol, while in the 4-ME2 group only esterified cholesterol decreased. High density lipoproteins were significantly elevated in the E2 treated group. However, there was an increase in very low density lipoproteins and a decrease in low density lipoproteins in 2-ME2 and 4-ME2 treated groups. These results suggest that catechol estrogens may play an important role in the lipoprotein metabolism and atherosclerotic diseases, and the mechanism of action may differ from that of estradiol.

2-Methoxyestradiol↗
PubMed1984

Effect of pregnancy plasma, neuraminidase and sialic acid on phytohemagglutinin-induced human lymphocyte response.

The effect of human pregnancy plasma on phytohemagglutinin-(PHA-)induced blastogenesis of lymphocytes from unrelated donors was studied in relation to the sialic acid (N-acetyl-neuraminic acid) content of the plasma. The total sialic acid levels in plasma were found to be elevated during pregnancy as compared with plasma from non-pregnant, normally menstruating control groups (p less than 0.001) and to increase with advancing gestation, reaching peak values in the post-partum period (1-14 days). On the other hand, pregnancy plasma at a concentration of 15% caused a significant suppression of lymphocyte proliferation (p less than 0.05 to p less than 0.001, depending on the stage of gestation). The maximum effect was observed with plasma obtained during the third trimester of pregnancy. The immunosuppressive activity was not detectable after parturition. It was further observed that desialation of both pregnancy and control plasma with neuraminidase diminished lymphocyte response to PHA (p less than 0.05). Addition of free sialic acid (0.1-1.0 mumol/ml) or treatment of the cells with neuraminidase (0.06-1.0 IU/ml) had no effect on lymphocyte transformation under assay conditions. These findings support the hypothesis that an immunosuppressive environment provided by pregnancy plasma could be one of the mechanisms protecting the antigenically alien fetus from maternal immunologic attack. The sialic acid content of maternal plasma did not appear to play a role in the immunosuppressive property of maternal plasma. On the contrary, the presence of plasma-bound sialic acid in the culture medium was found to be necessary for normal lymphocyte reactivity.

Blood Physiological Phenomena↗
PubMed1983

Sialic acid, sialyltransferase and neuraminidase levels in maternal plasma, urine and lymphocytes during pregnancy and post-partum period--a longitudinal study in women.

The total sialic (N-acetylneuraminic acid) levels were serially determined in maternal plasma, urine and lymphocytes during human pregnancy and post-partum period. The enzymes, sialyltransferase and neuraminidase, were also examined in the plasma samples. The sialic acid content of plasma and urine (expressed in terms of the creatinine content in urine) was elevated during pregnancy and increased with advancing gestation (P less than 0.001). A few days (0-6) prior to parturition there was a significant (P less than 0.01) fall in the plasma sialic acid levels, which subsequently increased again in the post-partum period (1-14 days), reaching values even greater than that observed during pregnancy. On the other hand, there was no decrease in the urinary sialic acid levels before delivery, and the post-partum values in urine, though higher than the values obtained in non-pregnant women, were not significantly greater than the levels observed during pregnancy. The sialic acid levels in lymphocytes were not altered during pregnancy. There was also no statistically significant change in serum sialyltransferase activity at any stage of pregnancy or post-partum period, while neuraminidase was not detectable in any of the plasma samples. The results are discussed with reference to the role of circulating sialic acid during pregnancy.

Adult↗
PubMed1983

Efferent effects elicited by electrical stimulation at the round window of the guinea pig.

We report a technique for activating the efferent nerve fibres to the cochlea by electrical stimulation at the round window. Such electrical stimulation caused a reduction in the amplitude of the gross nerve response (N1) to a click presented after the electrical stimulus but did not alter the latency of the response. The reduction increased with increasing current strength above 200 microA and increasing rate of electrical pulses above 50 Hz. The effect was also dependent on the duration of the shock train and the pulse width. The reduction in N1 was most pronounced at low click intensities. Recovery of the N1 was almost complete about 80 ms after the end of the electrical stimulus. The effect of electrical stimulation in reducing the N1 amplitude could almost always be blocked by intraperitoneal injections of strychnine. Recovery from the strychnine block was observed when animals were maintained for periods of more than 60 min after the administration of strychnine. The ease of this technique allows it to be used to examine the effects of efferent stimulation on various aspects of cochlear function in the guinea pig.

Animals↗
PubMed1983

Crossed cochlear influences on monaural temporary threshold shifts.

Temporary threshold shifts (TTS) of the cochlear action potential in one (ipsilateral) ear, caused by a brief intense pure tone, were reduced either by (1) contralateral acoustic stimulation at the same frequency, or (2) destruction of the contralateral cochlea. The effect of contralateral cochlear destruction persisted, though slightly reduced in effect, after a delay of one hour between the destruction and the ipsilateral exposure. Contralateral acoustic stimulation had no effect after a delay of 10 min. The effect of contralateral cochlear destruction could be blocked by strychnine, a known antagonist of auditory efferent activity. However, contralateral cochlear destruction resulted in none of the effects upon normal ipsilateral thresholds or input-output curves for the action potential classically seen when the efferent pathways are stimulated. The results suggest that the crossed effects reported here are due to a complex interaction between the activity in both cochleas, possibly resulting in a reduction in a central inhibitory influence on an efferent feedback pathway that is then expressed during the ipsilateral exposure.

Acoustic Stimulation↗
PubMed1983

Residual effects in monaural temporary threshold shifts to pure tones.

Temporary threshold shifts (TTS), of the cochlear action potential in the guinea pig, caused by a high frequency exposure tone could be reduced by a prior exposure at the same frequency but lower intensity. The TTS caused by the initial, low intensity exposure tone was allowed to recover to levels where the thresholds were not significantly different from normal thresholds. Re-exposure at the high intensity now resulted in less TTS being recorded, both at the half-octave point and across the range of frequencies affected by the pure tone, when compared to exposure to the high intensity tone without such priming. This protective effect of prior exposure was not affected by intraperitoneal injections of strychnine, distinguishing it from recent reports of protective mechanisms operative during TTS.

Acoustic Stimulation↗
PubMed1982

Estrogen effects on NADH oxidase and superoxide dismutase i prepubertal female rats.

Thirty-four day old, ovariectomised rats were treated with increasing doses of estradiol, 2-hydroxyestradiol 2,3-dimethyl ether (23E2), 4-hydroxyestradiol 3,4-dimethyl ether (34E2) and 4-methoxyestradiol (4ME2) for five days by subcutaneous injection. Superoxide dismutase, phenol activated NADH oxidase and uterine dry weights were determined. Only estradiol was found to be uterotrophic and increased NADH oxidase activity in these experiments. Both 23E2 and 34E2 treatment reduced the enzyme activity significantly. Though 4ME2 showed a decrease in NADH oxidase at 0.05 micrograms/100 gm body weight there was no further decrease at higher dose (5 micrograms/100 gm). The superoxide dismutase (SOD) in uterus and liver was unaffected by estradiol, while 23E2, 34E2, and 4ME2 significantly reduced SOD in both liver and uterus. These results indicate that 23E2, 34E2 and 4ME2, in spite of their nonuterotrophic property property, affect uterine metabolism. Furthermore, in view of the reports indicating the importance of SOD levels in various tumors and since catecholestrogens are observed to reduce SOD levels in liver and uterus, it is suggestive that catecholestrogens may play an important role in the pathophysiology of certain tumors.

Animals↗
PubMed1981

Synthesis of catechol estrogens by human uterus and leiomyoma.

Homogenates of human endometrial, myometrial and leiomyoma tissues were incubated with (2,4,6,7-3H)-estradiol and tritiated catechol estrogens were isolated and identified. Though 2- and 4-hydroxylations were about the same in endometrium, 4-hydroxylation was two to four fold higher than 2-hydroxylation in myometrium and leiomyoma. However, endometrium showed greater capacity to form both 2- and 4-hydroxyestrogens than the other two tissues. Both 2- and 4-hydroxylations were significantly less than in myometrium. In view of the reports indicating that inhibitors of catechol 0-methyl transferase (COMT) might act as antineoplastic agents due to their interference with t-RNA methylases and since catechol estrogens inhibit COMT, the present results suggest that endogenous synthesis of catechol estrogens may play an important role in the pathophysiology of uterine leiomyoma.

Aryl Hydrocarbon Hydroxylases↗
PubMed1981

Oestrogen metabolism in adult rat's brain.

In vitro incubation of pituitary, hypothalamus and cerebral cortex with [3H]oestrogens revealed that the oestrogens are actively metabolized by these tissues. The covalent binding of oestrone and oestradiol to acid precipitable proteins was observed. Pituitary from male rats exhibited higher covalent binding of oestrogens than females. The 2-hydroxylation was found to be greater than 16-hydroxylation. Furthermore, male pituitary exhibited higher 2-hydroxylation of oestrogens than females. No such sexual dimorphism was observed in 16-hydroxylation. C17-reduction was found to be greater than oxidation in these tissues. Furthermore, the C17-reduction in pituitary and hypothalamus from females was greater than males, which is in contradistinction to protein binding and 2-hydroxylation of oestrogens. In both male and female animals the pituitary was metabolically more active than hypothalamus and cortex. In addition, oestradiol was hydroxylated more than oestrone either at 2- or 16-positions. These results indicate that in central nervous system and pituitary the oestrogens are metabolized preferentially by 2-hydroxylation pathway and it is suggested that the in situ metabolism of oestrogens in neuroendocrine tissues may be important in the control of oestrogen effects on neuroendocrine function and sex behaviour.

Age Factors↗
PubMed1980

Estrogen metabolism in neural tissues of six-day-old rats.

In vitro incubation of pituitary, hypothalamus and cerebral cortex from 6-day-old rats with [6,7-3H]estradiol revealed that estradiol is actively metabolized in these tissues. Pituitary was found to be more active than hypothalamus and cerebral cortex in metabolizing estradiol in these animals. Covalent binding of estradiol to acid-precipitable proteins was observed in all these tissues from both sexes. While there was no significant sex difference in protein binding of estradiol in any of the tissues tested, treatment with progesterone or estradiol valerate increased protein binding. 2- and 16-hydroxylation and 17 beta-oxidation were demonstrated in all the tissues tested. While there were no significant sex differences observed in 2,16-hydroxylation, 17 beta-oxidation appeared to be more in males. Progesterone treatment of males increased 2-hydroxylation of estradiol 4-fold in pituitary and doubled the levels in hypothalamus. 16-Hydroxylation and 17-oxidation were also elevated significantly in pituitary and hypothalamus by progesterone treatment. Estradiol valerate treatment, however, decreased 2-hydroxylation and 16-hydroxylation in pituitary and hypothalamus; 17-oxidation was increased in pituitary. These results suggest that the estradiol metabolism, and especially 2-hydroxyestradiol formation, can be increased by progesterone and thereby mediate antagonistic effect of progesterone on estrogen-mediated brain sexual differentiation.

Animals↗