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Biomedical subjects

S Y Hsu

Publications and source records attributed to S Y Hsu.

At least 55 records · Page 3Linked to original sources
PubMed1997

Interference of BAD (Bcl-xL/Bcl-2-associated death promoter)-induced apoptosis in mammalian cells by 14-3-3 isoforms and P11.

Apoptosis and survival of diverse cell types are under hormonal control, but intracellular mechanisms regulating cell death are unclear. The Bcl-2/Ced-9 family of proteins contains conserved Bcl-2 homology regions that mediate the formation of homo- or heterodimers important for enhancing or suppressing apoptosis. Unlike most other members of the Bcl-2 family, BAD (Bcl-xL/Bcl-2 associated death promoter), a death enhancer, has no C-terminal transmembrane domain for targeting to the outer mitochondrial membrane and nuclear envelope. We hypothesized that BAD, in addition to binding Bcl-xL and Bcl-2, may interact with proteins outside the Bcl-2 family. Using the yeast two-hybrid system to search for BAD-binding proteins in an ovarian fusion cDNA library, we identified multiple cDNA clones encoding different isoforms of 14-3-3, a group of evolutionally conserved proteins essential for signal transduction and cell cycle progression. Point mutation of BAD in one (S137A), but not the other (S113A), putative binding site found in diverse 14-3-3 interacting proteins abolished the interaction between BAD and 14-3-3 without affecting interactions between BAD and Bcl-2. Because the S137A BAD mutant presumably resembles an underphosphorylated form of BAD, we used this mutant to screen for additional BAD-interacting proteins in the yeast two-hybrid system. P11, a nerve growth factor-induced neurite extension factor and member of the calcium-binding S-100 protein family, interacted strongly with the mutant BAD but less effectively with the wild type protein. In Chinese hamster ovary (CHO) cells, transient expression of wild type BAD or its mutants increased apoptotic cell death, which was blocked by cotransfection with the baculovirus-derived cysteine protease inhibitor, P35. Cotransfection with 14-3-3 suppressed apoptosis induced by wild type or the S113A mutant BAD but not by the S137A mutant incapable of binding 14-3-3. Furthermore, cotransfection with P11 attenuated the proapoptotic effect of both wild type BAD and the S137A mutant. For both 14-3-3 and P11, direct binding to BAD was also demonstrated in vitro. These results suggest that both 14-3-3 and P11 may function as BAD-binding proteins to dampen its apoptotic activity. Because the 14-3-3 family of proteins could interact with key signaling proteins including Raf-1 kinase, protein kinase C, and phosphatidyl inositol 3 kinase, whereas P11 is an early response gene induced by the neuronal survival factor, nerve growth factor, the present findings suggest that BAD plays an important role in mediating communication between different signal transduction pathways regulated by hormonal signals and the apoptotic mechanism controlled by Bcl-2 family members.

14-3-3 Proteins↗
PubMed1996

Targeted overexpression of Bcl-2 in ovaries of transgenic mice leads to decreased follicle apoptosis, enhanced folliculogenesis, and increased germ cell tumorigenesis.

We have generated transgenic mice overexpressing Bcl-2, an apoptosis suppression protein, in ovarian cells using the inhibit-alpha gene promoter/enhancer. Ovarian apoptotic DNA fragmentation induced in immature animals by a low dose (2 IU) of PMSG was suppressed by greater than 55% in transgenic mice compared to their wild-type littermates. Morphological and in situ DNA end-labeling analyses showed that granulosa cells in large antral follicles of wild-type animals undergo apoptosis, but most follicles in transgenic animals are healthy. When the animals were treated with a high dose (4 IU) of PMSG to stimulate follicular growth, spontaneous ovulation was observed in 14 of 23 (61%) of the transgenic animals, but in only 3 of 18 (17%) of wild-type siblings. Furthermore, transgenic females had a larger litter size (9.07 +/- 0.25 pups/litter; n = 29) than wild-type controls (7.54 +/- 0.26 pups/litter; n = 28; P < 0.01). These data suggested that decreased ovarian apoptosis in transgenic animals could lead to enhanced folliculogenesis and ovulatory potential. Moreover, aging transgenic mice are susceptible to the development of benign cystic ovarian teratoma (4 in 20 transgenic animals and 0 in 26 wild-type controls). Some tumor tissues showed respiratory and intestinal cell types, whereas others showed the development of central nervous system-like structures. Because the bcl-2 transgene in these animals is overexpressed in somatic cells, but not oocytes, these findings suggest that enhanced survival of selected somatic cells in transgenic mice could lead to germ cell tumorigenesis. Thus, overexpression of Bcl-2 protein in the ovary leads to decreased ovarian somatic cell apoptosis, enhanced folliculogenesis, and increased susceptibility to ovarian germ cell tumorigenesis in transgenic animals. The present mouse model allows future studies on intracellular signal pathways regulating follicular atresia and on the potential role of ovarian somatic cell factors in germ cell tumorigenesis.

Aging↗
PubMed1996

Food-borne disease outbreaks in Taiwan, 1994.

In 1994, 102 outbreaks of food-borne disease involving 4,726 cases were reported to the Taiwan Department of Health. This is the highest number of outbreaks and cases in recent years in Taiwan. Of these outbreaks, 72.5% (74/102) were caused by bacterial pathogens, with Vibrio parahaemolyticus responsible for 56.7% (42/74), Staphylococcus aureus 20.3% (15/74), Bacillus cereus 14.9% (11/74) and Salmonella spp other than S. typhi and S. paratyphi 8.1% (6/74). V. parahaemolyticus has been a leading cause of problems in Taiwan for many years. Contamination of seafood with this organism has been reported frequently, particularly in the warmer months. In 1994, small outbreaks (fewer than 5 cases) and large outbreaks (more than 50 cases) represented 31.4% (32/102) and 12.7% (13/102), respectively, of the total. The median outbreak size was 10 cases. A high proportion (54%, 7/13) of the large outbreaks was associated with commercial lunch-boxes supplied to elementary and junior high schools. Health education to improve food sanitation and supervision of food sanitation practices need to be strengthened.

Bacillus cereus↗
PubMed1996

Gonadal cell apoptosis.

Apoptosis is an important cellular process by which superfluous or unwanted cells are deleted from an organism during tissue remodeling and differentiation. Recent studies have demonstrated the role of this programmed cell death or "controlled cell suicide" in the physiological function of an organism. Suppression of apoptosis increases the susceptibility of an individual to malignancy whereas uncontrolled cell death is associated with degenerative diseases. Normal development of both female and male gonads is characterized by massive cell death. More than 99% of ovarian follicles endowed at early life are destined to undergo apoptosis and the exhaustion of these follicles serves as a "clock" for female reproductive senescence. In the testis, up to 75% of male germ cells also undergo apoptosis, perhaps as a mechanism to delete superfluous or defective germ cells. Gonadal cell apoptosis provides valuable models to study hormonal regulation of apoptosis. In the ovary, gonadotropins, estrogens, growth hormone, growth factors (IGFI, EGF/TGF-alpha, basic FGF), cytokine (interleukin-1 beta) and nitric oxide act in concert to ensure the survival of preovulatory follicles. In contrast, androgens, interleukin-6 and gonadal GnRH-like peptide are apoptotic factors. Developmental studies further indicate that fractions of endowed follicles are recruited throughout the reproductive life whereas most of the primordial follicles are "arrested" at the initial stage of development for a prolonged time. Because a transcriptional factor WT1 is expressed in high levels in follicles at early stages of development and because WT1 over-expression represses the promoter activity of inhibin-alpha gene, this nuclear protein may be important in the maintenance of follicles at early stages of development. Once a cohort of follicles is recruited to grow, it is destined to undergo apoptosis unless rescued by survival factors. After puberty onset and under gonadotropin stimulation, some of the growing antral follicles are "selected" to continue their final maturation and secrete high levels of estrogens to trigger ovulation. Following repeated cycles of recruitment, atresia or ovulation, the follicle reserve is exhausted, thus signaling the onset of reproductive senescence. Although the somatic granulosa cell is the major cell type undergoing apoptosis in the ovary, the germ cells in the testis also exhibit signs of apoptotic cell demise. In the testis, gonadotropins and androgens act as survival factors whereas exposure to elevated temperature in cryptorchid testes increases apoptosis. In the seasonally breeding hamster model, photoperiod-entrained regression and recrudescence of testis tissue serves as a unique natural model of apoptosis. With recent advances in our understanding of the cellular mechanism of apoptosis, including the elucidation of the Ced9/bc12 and Ced3/ICE family of proteins, further investigation of gonadal apoptosis may lead to a better understanding of gonadal degenerative disorders (such as premature ovarian failure and oligospermia), reproductive senescence and tumorigenesis. The gonadal model should also be valuable in studying the regulation of intracellular apoptosis genes by external hormonal signals.

Animals↗
PubMed1995

Genetic heterogeneity of constitutively activating mutations of the human luteinizing hormone receptor in familial male-limited precocious puberty.

Genomic DNA from 32 unrelated families with male-limited precocious puberty was examined for the previously described Asp-578-->Gly, Met-571-->Ile, and Thr-577-->Ile mutations in transmembrane helix 6 of the human luteinizing hormone receptor (hLHR). Twenty-eight families had the inherited form of the disorder, and of these, 24 were found to have the Asp-578-->Gly mutation. Four additional mutations were found among the remaining four families with the inherited form and in four sporadic cases of the disorder: an A-->C transversion resulting in substitution of leucine for Ile-542 in the fifth transmembrane helix, an A-->G transition resulting in substitution of glycine for Asp-564 in the third cytoplasmic loop, a G-->T transversion resulting in substitution of tyrosine for Asp-578 in the sixth transmembrane helix, and a T-->C transition resulting in substitution of arginine for Cys-581 in the sixth transmembrane helix. Human embryonic kidney cells transfected with cDNAs for each of the mutant hLHRs, created by PCR-based mutagenesis of the wild-type hLHR cDNA, exhibited increased levels of basal cAMP production in the absence of agonist, indicating constitutive activation of the mutation hLHRs. Three of the additional mutations had specific features: Ile-542-->Leu and Cys-581-->Arg appeared ligand-unresponsive, whereas Asp-578-->Tyr appeared to correlate genotype with phenotype. We conclude that the region spanning nt 1624-1741 of exon 11 is a hotspot for heterogeneous point mutations that constitutively activate the hLHR and cause male-limited precocious puberty.

Amino Acid Sequence↗
PubMed1995

Calcium supplementation and bone mineral density in postmenopausal women using estrogen replacement therapy.

Both estrogen and calcium have been shown to be of benefit in reducing the incidence of osteoporosis in postmenopausal women. It has been suggested that estrogen promotes the intestinal absorption of calcium, and this effect may especially benefit postmenopausal women with a low dietary intake of calcium. The purpose of this study was to examine the effect of calcium supplementation on the bone mineral density (BMD) of postmenopausal women using estrogen replacement therapy. BMD measurements were made over 12 months in two groups of postmenopausal women, one having treatment with estrogen alone, and the second having estrogen and 1000 mg of supplemental calcium each day. There was no significant reduction in BMD between the two groups over the 12-month study period. Those in the group having supplemental calcium had a significant increase in BMD at the femoral neck (p = 0.023), but not in other areas of the femur nor in the lumbar spine. The results of this study suggest that the addition of supplemental calcium may improve the bone mass of postmenopausal women using estrogen who have a low dietary calcium intake. This benefit appears to be more pronounced in corticocancellous than in trabecular bone, and may therefore have a greater effect on the femoral neck than the lumbar spine.

Absorptiometry, Photon↗
PubMed1995

Different 5'-flanking regions of the inhibin-alpha gene target transgenes to the gonad and adrenal in an age-dependent manner in transgenic mice.

The inhibin-alpha gene is expressed in a tissue-specific manner, and its protein product dimerizes with one of two beta-subunits to form bioactive heterodimers. To characterize the cis-acting elements involved in directing gonad- and adrenal-specific expression of inhibin-alpha, transgenic mice were generated that carried 2.5 or 6 kilobases (kb) of the 5'-flanking region of the mouse inhibin-alpha gene driving the human bcl-2 complementary DNA. Using an antibody specific for human Bcl-2, Western blotting and immunocytochemical analyses showed that both enhancer/promoter fragments direct transgene expression to the ovary, testis, and adrenal gland. The 6-kb fragment targeted the ovarian transgene expression in interstitial cells and young corpora lutea as well as granulosa and thecal cells of secondary, antral, and preovulatory follicles. In ovaries of animals with the 2.5-kb fragment, transgene expression was also detected in interstitial cells and young corpora lutea, but only in granulosa and thecal cells from antral and preovulatory follicles. The ovarian transgene expression in animals carrying the 6-kb inhibin-alpha promoter/bcl-2 construct was stimulated by gonadotropin treatment, with greater than 10-fold increases observed 2 days after PMSG stimulation. In the testes of both types of transgenic animals, immunoreactive Bcl-2 was predominantly detected in Sertoli cells of seminiferous tubules. Sporadic expression was also observed in some interstitial cells. In the adrenal gland, reporter protein was detected in the zona fasciculata of both types of transgenic animals during adult life; however, transgene expression was detected in zona fasciculata of young (21-day-old) animals with the 6-kb, but not the 2.5-kb, promoter construct. Thus, the 2.5-kb inhibin-alpha 5'-proximal DNA sequence directs transgene expression in mature ovarian follicles and testicular Sertoli cells. In contrast, enhancer elements in the 6-kb fragment are required for expression in preantral follicles and in the adrenal of immature animals. The inhibin-alpha promoter/enhancer used here represents unique DNA sequences for ovarian-specific transgene expression and is useful for future analysis of gonadal and adrenal cell functions.

Adrenal Glands↗
PubMed1995

Wilms' tumor protein WT1 as an ovarian transcription factor: decreases in expression during follicle development and repression of inhibin-alpha gene promoter.

WT1, a gene deleted in some Wilms' tumors, encodes a transcription factor with zinc fingers and shares homology with proteins in the early growth response gene family. Although defects in the WT1 gene are associated with nephroblastoma and genitourinary malformation, the specific function of WT1 in the gonads remains unclear. We investigated the expression of WT1 transcripts in rat ovary during follicle development by Northern blotting, RNase protection assay, and in situ hybridization. Abundant WT1 transcripts were found in the ovary, testis, uterus, and kidney, with lower levels in the heart and pancreas. Treatment with estrogen or gonadotropins did not affect the concentration of ovarian WT1 mRNA. In situ hybridization analysis indicated that ovarian WT1 mRNA is expressed exclusively in the surface epithelium and granulosa cells of primordial, primary, and secondary follicles, and its levels decrease during follicle growth. Although RNase protection assay suggested the presence of four alternatively spliced forms of WT1 mRNA, the ratio of these transcripts remains constant during ovarian growth. Developmental changes in the expression of two granulosa cell differentiation marker genes, inhibin-alpha and FSH receptor, were found to be inversely correlated with WT1 levels. Because potential WT1-binding sites were found in the promoter of inhibin-alpha gene, we further tested whether WT1 might regulate the expression of this gene. Cotransfection of a WT1 expression vector with a promoter reporter plasmid of inhibin-alpha resulted in the repression of promoter activities in CHO cells in a dose-dependent manner. These results suggest that WT1 is expressed in high levels in granulosa cells of primordial, primary, and secondary follicles but decreases with follicle development. This transcription factor might be a repressor of ovarian differentiation genes in the granulosa cells and play a role in arresting the differentiation of immature follicles.

Animals↗
PubMed1994

High-performance liquid chromatographic determination of rutaecarpine in rat plasma: application to a pharmacokinetic study.

A simple and sensitive high-performance liquid chromatographic method for determination and identification of rutaecarpine in rat plasma has been developed. Up to 0.1 ml of plasma containing rutaecarpine was deproteinized by acetonitrile, which contained an internal standard (paeonol). The supernatant was injected onto a reversed-phase column using a acetonitrile-water-orthophosphoric acid (85%) (60:40:0.1, v/v/v, pH 2.5-2.8) as the mobile phase and ultraviolet detection at 344 nm. It was applied to the pharmacokinetic study of rutaecarpine in rat after a 2 mg/kg intravenous administration. A biphasic process with a rapid distribution followed by a slower elimination phase was observed from the plasma concentration-time curve. Compartmental analysis yielded a two-compartment model.

Acetophenones↗
PubMed1993

A longitudinal study of the determinants of bone mass in Chinese women aged 21 to 40. I. Baseline association of anthropometric measurements with bone mineral density.

The bone mineral density of the lumbar spine (L2 to L4) and neck of the femur of 293 Chinese women aged 21 to 40 years was measured using a dual x-ray densitometer. The participants were recruited from subjects registered with the University Family Medicine Clinic in Hong Kong. Our cross-sectional data showed that maximal bone mass occurs in the early 30s. Both the spine and hip bone masses were observed to decline at a rate of around 1% per annum from the early 30s onward. Body weight, lean body mass, and body fatness were significantly associated with the mineral density of the spinal and femoral bones after or around the attainment of peak bone mass, while no correlation of these data was observed in the younger age group (20 to 28 years). Other factors may play a more important role than body mass in influencing bone mineral density before attainment of peak bone mass.

Absorptiometry, Photon↗
PubMed1993

Cellular mechanisms for orthovanadate-, phorbol ester-, and calcium ionophore-stimulated prostaglandin production in brook trout (Salvelinus fontinalis) follicles.

Previous studies have shown that prostaglandin (PG) production in brook trout (Salvelinus fontinalis) follicles can be stimulated by sodium orthovanadate, phorbol-12 myristate 13-acetate ester (PMA), and the calcium ionophore, A23187. In the present study, the mechanisms by which these activators stimulate PG production in follicles were specifically investigated by examination of their effects on the release of 3H-labeled arachidonic acid (AA) from prelabeled follicles (AA release) and on the capacity to convert exogenous 3H-AA into prostanoids (AA conversion) by follicle walls. The release of AA from follicles was significantly stimulated by orthovanadate and A23187 after 4 h of incubation. Although AA release was not stimulated by PMA alone, levels of AA release in incubations with both PMA and A23187 were greater than in those with A23187 alone. In contrast, AA conversion in follicle walls was significantly increased by PMA and orthovanadate but not by A23187 alone. The results showed that 1) the calcium ionophore A23187 stimulated ovarian PG production mainly through its effects on the release of AA from follicles; 2) PMA enhanced follicular PG production through an increase in AA conversion in the follicle walls; and 3) orthovanadate mediated PG production by increasing both AA release and AA conversion. In addition, PMA-, A23187-, and orthovanadate-stimulated increases in AA release or conversion were significantly reduced by the translational inhibitor, cycloheximide, and the transcriptional inhibitor, actinomycin. These results indicate that PMA-, A23187-, and orthovanadate-stimulated AA release and AA conversion require protein synthesis and pretranslational activation in the follicles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The Johnson antishear device and standard shin pad in the isokinetic assessment of the knee.

Isokinetic training and assessment of the knee joint has been the mainstay of rehabilitation, especially in patients with anterior cruciate ligament deficiency. Besides the original shin pad used, the antishear device was introduced by Johnson in 1982. This device has been shown biomechanically to prevent excessive anterior translation of force on the tibia during training. However, there is a need to compare the antishear device and the standard shin pad in the isokinetic assessment. Hence, the major objective of this study is to define, if any, the difference in patient assessment between the new double pad device and the old single shin pad. Ten subjects with no previous history of injury on either knee were tested with the Cybex Isokinetic Dynamometer. There were four men and six women and the mean age was 25.2 years. They were randomized into different test sequences with different shin pads at different speeds. Correlation and paired t tests (P) were performed to find out the correlation and difference between the two devices. There was significant difference in performance assessment between the two devices in knee extension (P < 0.05) but no significant difference in knee flexion (P > 0.05). There was also a high correlation (r > 0.75) between the two devices. It is concluded that because of the significant difference of data generated between the two devices, it is important to select one single device with each patient during a series of testings.

Adult↗
PubMed1992

The effects of E and F prostaglandins on ovarian cAMP production and follicular contraction in the brook trout (Salvelinus fontinalis).

The effects of PGE1, PGE2, PGF2 alpha (2 micrograms/ml), and forskolin (10 microM) on follicle contraction of brook trout (salvelinus fontinalis) were studied by measuring the weight loss of punctured follicles during in vitro incubation. PGE1, PGE2, and forskolin significantly inhibited spontaneous contraction of follicles. In contrast, PGF2 alpha significantly increased the weight loss of punctured follicles. The results indicate that PGs could influence ovulation through their effects on follicle wall contraction. The effects of PGs and forskolin on cAMP production in follicles were also investigated by incubating intact follicles (without extrafollicular tissue), follicle walls, and denuded oocytes at pregerminal vesicle breakdown (preGVBD) and preovulatory (preOV) stages in vitro with PGE1, PGE2, PGF2 alpha (0.2 and 2 micrograms/ml), or forskolin (10 microM). At the end of incubation, cAMP content in incubation medium and follicular tissue was assayed by a specific protein-binding assay. Intact follicles in control groups contained high amounts of cAMP at both stages, but released significantly more cAMP into the medium at the preGVBD stage (P < 0.05). Forskolin stimulated significantly higher levels of cAMP in incubation medium at either stage. At the preGVBD stage, significantly higher cAMP levels were measured in the medium with higher dose of PGE1 at 1 and 4 hr and with higher dose of PGE2 at 1, 2, and 4 hr. Significantly higher cAMP levels were also measured in incubates with high dose of PGE1 at 2 and 4 hr and with high doses of PGE2 at 2, 4, and 16 hr at the preOV stage. However, follicular cAMP levels were significantly elevated only by forskolin at both stages. Experiments incubating only follicle walls or denuded oocytes demonstrated that most of the medium cAMP measured in preGVBD intact follicle incubates was derived from denuded oocytes, and that the stage difference in cAMP release within intact follicle incubates was due to a stage difference in cAMP release from denuded oocytes. In addition, follicle walls appeared to be more sensitive to forskolin and PG stimulations than denuded oocytes. The stimulation of cAMP accumulation in the medium by PGEs may be significant since both forskolin and PGEs have been shown to inhibit brook trout ovulation in vitro (F. W. Goetz, D. C. Smith, and S. P. Krickle (1982). Gen. Comp. Endocrinol. 48, 154-160) and follicle contraction in the present study.

Animals↗
PubMed1992

Inhibition of angiotensin-I-converting enzyme by tetrahydroxyxanthones isolated from Tripterospermum lanceolatum.

Five tetrahydroxyxanthones, 3,4,6,7-tetrahydroxyxanthone [1], 1,3,5,6-tetrahydroxyxanthone [2], 3,4,5,6-tetrahydroxyxanthone [3], 1,3,6,7-tetrahydroxyxanthone [4], and 2,3,6,7-tetrahydroxyxanthone [5] isolated from Tripterospermum lanceolatum inhibited angiotensin-I-converting-enzyme activity in a dose-dependent manner. The mode of inhibition of the tetrahydroxyxanthones (THXs) was found to be competitive inhibition. When the tetrahydroxy groups of THXs were blocked with acetyl groups, the angiotensin-I-converting-enzyme inhibitory activity was abolished, suggesting that the tetrahydroxy groups are indispensible for the inhibitory activity.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Haemodynamic effects of dicentrine, a novel alpha 1-adrenoceptor antagonist: comparison with prazosin in spontaneously hypertensive and normotensive Wistar-Kyoto rats.

1. The haemodynamic effects of dicentrine, an aporphine derivative isolated from the plant Lindera megaphylla, were investigated and compared with prazosin in rats. 2. In anaesthetized normotensive Wistar-Kyoto (WKY) rats, i.v. administration of dicentrine (0.1, 0.5, 1.0 mg kg-1) and prazosin (0.01, 0.05, 0.1 mg kg-1) induced a dose-related reduction of mean arterial pressure (MAP) which reached a maximal effect 5-10 min after injection and persisted for 2 h. 3. In anaesthetized WKY rats, a higher dose of dicentrine (1.0 mg kg-1, i.v.) did not cause any significant changes in heart rate (HR), cardiac output (CO) and stroke volume (SV) but markedly increased tail blood flow. In contrast, a higher dose of prazosin (0.1 mg kg-1, i.v.) produced a decrease in HR which paralleled the time course of the hypotensive response. 4. The hypotensive activity of dicentrine was completely abolished by alpha-adrenoceptor blockade. Both dicentrine and prazosin significantly attenuated pressor responses to noradrenaline but failed, even at maximal hypotensive doses, to impair the pressor effects of angiotensin II or vasopressin. These observations suggest that dicentrine appears to exert its hypotensive action through alpha 1-adrenoceptor blockade. 5. In conscious normotensive and spontaneously hypertensive (SH) rats, dicentrine (0.5-2.0 mg kg-1, i.v.) and prazosin (0.05-0.2 mg kg-1, i.v.) also evoked dose-related decreases in MAP which were of greater magnitude in SH rats. Oral administration of dicentrine (5 and 8 mg kg-1) to conscious SH rats caused a hypotensive effect which persisted for over 15 h.6. These results suggest that dicentrine may have therapeutic potential as an oral antihypertensive drug via alpha-adrenoceptor blockade.

Adrenergic alpha-Antagonists↗
PubMed1992

Oxoanions stimulate in vitro ovulation and signal transduction pathways in goldfish (Carassius auratus) follicles.

The present study investigated the effects of a number of oxoanion compounds on in vitro ovulation of goldfish follicles and ovarian second messenger activities. Significant levels of ovulation were induced by 0.1 mM sodium chromate, 0.1 mM sodium metavanadate, 10 mM sodium molybdate, 0.1 mM sodium orthovanadate, 5 mM sodium selenate, 0.5 mM sodium tungstate, and 0.1 mM vanadyl sulfate. At levels that significantly stimulated ovulation, metavanadate, molybdate, orthovanadate, tungstate, and vanadyl sulfate also stimulated follicular phosphatidylinositol cycling and inhibited ovarian alkaline phosphatase activity. Moreover, the ovulation induced by these oxoanions was not inhibited by indomethacin (10 micrograms/ml), while ovulation induced by selenate and chromate was. In contrast, only vanadium-containing compounds significantly stimulated prostaglandin (PG) synthesis, and, in fact, selenate significantly inhibited PG production. Finally, only sodium molybdate- and vanadium-containing compounds appeared to increase follicular adenosine 3',5'-cyclic monophosphate content. While all oxoanions stimulated in vitro ovulation, they had differential effects on certain signal transduction pathways when tested at concentrations that stimulated in vitro ovulation. From the results, two basic groups could be delineated, one containing tungstate-, molybdate-, and vanadium-containing compounds and the other selenate and chromate. Thus the mechanism by which ovulation is induced by chromate and selenate may be different from that of vanadium-containing compounds, molybdate, and tungstate.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗