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Biomedical subjects

U K Banik

Publications and source records attributed to U K Banik.

18 recordsLinked to original sources

Inhibition of proprotein convertases-1, -7 and furin by diterpines of Andrographis paniculata and their succinoyl esters.

Studies were performed to investigate the prohormone/proprotein convertase (PC)-inhibitory properties of chemical constituents of the medicinally active plant Andrographis paniculata (AP; from the family Acanthaceae), also known as 'King of Bitters'. Among the individual components tested against the clinically important convertases, furin and PC1, neoandrographolide (a C3 O-glucoside derivative of the major constituent andrographolide) exhibited the highest inhibitory action with an IC50 of 53.5 microM against furin. The data further revealed that although andrographolide, the major bitter principle of AP, exhibited a relatively small enzyme inhibition (IC50=1.0 mM and Ki=200 microM against furin), upon succinoylation, its inhibitory action against the above convertases was enhanced significantly with a Ki in the low micromolar range (<30 microM), suggesting that a specific structural modification of the andrographolide skeleton may be exploited to develop a new class of non-peptide inhibitors of PCs. When tested against PC7, these succinoylated derivatives of andrographolide also displayed strong inhibitory action, with Ki values again in the low micromolar range. This potentially interesting observation may be attributed to the reported anti-HIV property of 14-dehydroandrographolide succinic acid monoester (DASM). It is suggested here that DASM, by virtue of this protease inhibitory property, possibly acts by suppressing the proteolytic cleavage of envelope glycoprotein gp160 of HIV, which is known to be PC-mediated, particularly by furin and PC7.

Anti-HIV Agents↗

A simple and sensitive nonradioactive method for the detection of urinary human chorionic gonadotropin and diagnosis of early human pregnancy. I. Multiple-unit test.

A simple, sensitive, and reproducible method for the detection of urinary human chorionic gonadotropin (hCG) and diagnosis of early human pregnancy is reported. A 5-ml aliquot of filtered early-morning urine sample was concentrated in a microconcentrator (M) to 0.1 ml of retentate which was diluted with 0.4 ml of distilled water and tested in a hemagglutination inhibition test (M-HIT). Also, a 0.1-ml aliquot of filtered unconcentrated urine sample was diluted with 0.4 ml of distilled water and tested in the same hemagglutination inhibition test (HIT). Urine samples from women of reproductive age; from perimenopausal, menopausal, and proteinuric women; and from adult males were tested in the HIT and M-HIT. Some of these urine samples were also tested in the mouse ovulation bioassay (MOB). The M-HIT was significantly more reliable than the HIT for diagnosis of early pregnancy 25 to 55 days after menses. Correct negative results with the M-HIT were obtained in urine samples of most of the nonpregnant cycling, perimenopausal, and menopausal women, and adult males. Urine samples from subjects with severe proteinuria gave false-positive types of reactions in the M-HIT. Positive results were obtained in the MOB with a number of urine samples from pregnant, perimenopausal, and menopausal women. A properly conducted M-HIT should be very valuable in diagnosing pregnancy as early as the 26th day of the cycle in regularly menstruating women.

Chorionic Gonadotropin↗

A simple and sensitive nonradioactive method for the detection of urinary human chorionic gonadotropin and diagnosis of early human pregnancy. II. Single-unit test.

A simple, sensitive, and reliable single-unit nonradioactive method for the detection of human chorionic gonadotropin (hCG) in concentrated urine and the diagnosis of early pregnancy is reported. This unit, presently termed the Ayerst pregnancy test kit (APTK), consists of four components: a sampler-filter paper cone, an ultrafilter-concentrator to which a vial holder is attached, a support stand with a mirror, and an immunologic reagent vial. In the APTK, 5 to 6 ml of urine were sampled, filtered, and concentrated, and the hCG in the retentate was detected by Ayerst immunologic reagents [APTK(AY)] and by the Pregnosticon "All In" [APTK(P)]. Some of the unconcentrated urine samples (0.1 ml) were also tested in hemagglutination inhibition tests (HIT) using Ayerst [HIG(AY)] and Pregnosticon "All In" [HIT(P)] reagents. Urine samples from pregnant, nonpregnant (ovulating and nonovulating), perimenopausal, and menopausal women were tested. It was found that the APTK(AY) and APTK(P) were significantly more sensitive and reliable than the HIT(AY) and HIT(P) in detecting low levels of urinary hCG for early diagnosis of pregnancy. The sensitivity and specificity of the APTK(AY) were better than those of the APTK(P). The APTK(AY) give significantly more correct positive and negative results than the other tests performed simultaneously. The APTK(AY) is simpler and safer than the serum radioimmunoassays and radioreceptor assay presently used to detect low levels of hCG for the early diagnosis of pregnancy and other hCG-producing states.

Chorionic Gonadotropin↗

Effects of a luteinizing hormone-releasing hormone analog on mating and fertility in rats.

A rhythmic antifertility effect of a luteinizing hormone-releasing hormone (LH-RH) analog, [D-Ala6-des-Gly-NH210]-LH-RH-ethylamide (AY-25,205), administered intramuscularly every 3rd day staring in the afternoon of diestrus, was demonstrated in 4-day cyclic rats. The antifertility effect was achieved for a period of approximately four cycles when the females were allowed constant cohabitation with fertile males except for 24 hours following treatment. Unrestricted cohabitation resulted in some matings and pregnancies in the group treated every 3rd day and also in some of the groups treated every 4th day with restricted cohabitation. The antifertility effect of AY-25,205, with unrestricted cohabitation, disappeared when the second treatment was given 4 days after the first. It is presumed that the antifertility effect of AY-25,205 was achieved through its capacity to induce ovulation at a physiologically "wrong time" (i.e., 1 day before the expected day of proestrus) and through its effect on mating behavior. The present experimental models suggest that AY-25,205 or similar analogs could be potentially useful for a more reliable rhythm method of birth control in humans, by timing ovulation and narrowing the fertile period of the cycle.

Animals↗

Pregnancy-terminating effect of human chorionic gonadotrophin in rats.

A single intramuscular dose of HGC(50) i.u. or more per rat) was able to induce fetal resorption and eventual termination of pregnancy when injected on Day 4 or between days 7 and 11 of pregnancy. This dose was inactive when administered on Day 12 of pregnancy. A single large dose (500 i.u./rat) induced fetal resorption when administered even on Day 12 of pregnancy. In intact rats treated with HCG, daily doses of progesterone were unable to maintain normal implantation; in ovariectomized rats treated with HCG, daily preges. Terone did succeed in maintaining pregnancy in many of the animals. It is suggested that fetal resorption and the eventual pregnancy-terminating effects of HCG in rats are mediated through the alteration of normal ovarian steroidogenesis.

Animals↗

Ovulation induction and antifertility effects of an LH-RH analogue (AY 25,205) in cyclic rats.

Pro-oestrous rats, treated with fluphenazine dihydrochloride to block ovulation, were used to compare the ovulation-inducing activity of synthetic LH-RH with one of its analogues, [D-Ala-6, des-Gly-NH2-10]-LH-RH ethylamide (AY-25,205). The lowest dose of LH-RH which produced a significant response was 125 ng compared with 2.9 ng AY-25,205. Statistical analysis of the data showed that AY-25,205 was approximately thirty-six times more potent than LH-RH. Treatment with AY-25,205 also induced partial ovulation in metoestrous rats (80 or 160 ng/rat) and apparently normal ovulation in dioestrous rats (10 to 160 ng/rat). The compound (160 ng) failed to induce further ovulation in oestrous rats which ovulated during the previous night. Advancement of premature ovulation in dioestrous rats with AY-25,205 prevented mating behaviour and pregnancy during the treatment cycle. The antifertility effect of the compound disappeared during the following cycle.

Animals↗