Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study analyses the manner in which trophoblast cells adhere to uterine epithelium and the subsequent interactions that contribute to the establishment of epitheliochorial placentation in the alpaca Lama pacos. Specimens at the luteal and follicular phases and at 22, 26, 30 and 45 days of pregnancy (op) were processed for morphological studies. On day 15 op, the blastocysts are completely free within the uterine lumen, with implantation starting around day 20. On days 22 and 26 of gestation, the trophoblast is apposed to the epithelial surface of the uterus, with areas of contact and adhesion by means of complex interdigitation. Implantation sites occur prevalently in the left uterine horn, but an expanded trophoblast also occupies large extensions of the right horn, where the maternofetal interaction shows peculiar areas of apposition. As development continues, attachment areas become more extensive. On days 30 and 45, many secretory granules can be seen in the uterine epithelium, while giant multinucleate cells appear interposed between the remaining trophoblast cells, showing intense alkaline phosphatase activity, deposits containing iron and PAS-positive granules. Placental lactogen hormone is not present within the cytoplasm of the binucleate or multinucleate trophoblast cells. By day 30 of gestation, the trophoblast layer is lined by an extraembryonic connective tissue that by day 45 is well vascularized, thus indicating the starting point of placental formation. Fetal and maternal capillaries indent the epithelium and the trophoblast, narrowing the specialized areas of exchange, which occur along the entire maternofetal interface, characterizing the diffuse nature of this placenta.
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PMID:Developmental changes at the materno-embryonic interface in early pregnancy of the alpaca, Lamos pacos. 1457 54

Automated system of image analysis Allegro-MC is described, including its scheme and concise characteristic. System is used for automated macro- and micromorphometric studies. As the examples for the demonstration of system operation the following micropreparations were used: capillaries of rat uterus, demonstrated by Gomori alkaline phosphatase reaction, cerebral neurons, visualized using NADPH-diaphorase Hope and Vincent method, capillaries as demonstrated by electron microscopy. As a sample of macropreparation, carotid angiogram taken in direct projection, was used. The demonstration is supplemented by vital microscopic study of microvascular reaction in rat small intestinal mesenterium to irradiation with heliumneon laser.
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PMID:[Application of automated image analysis system Allegro-MC for morphometric research]. 1462 65

This research aims to test a new drug candidate based on a traditional medicinal herb, F1, an herbal extract obtained from Astragalus membranaceus and its main ingredient, 1-monolinolein that may have fewer side effects and less uterine hypertrophy. In vitro experiments, human osteoblast-like cell lines, MG-63 and Saos-2, were analyzed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and an alkaline phosphatase (ALP) assays. Mouse osteoclasts were induced through a calcium-deficient diet and inhibition effects were measured. In vivo experiments were done using ovariectomized (OVX) rats for 9 weeks. At necropsy, uterus weights were measured, trabecular bone area (TBA) of tibia and lumbar vertebra were measured bone histomorphology. In results, cell proliferation and ALP activity in Saos-2 by ether F1 or 1-monolinolein did not increased significantly compared to the control. The F1 inhibited osteoclast development (IC25 = 3.37 x 10(-5) mg/mL) less than 17beta-estradiol. The OVX rats administered F1 (2 mg/kg/day and 10 mg/kg/day) showed an increase in TBA of the tibia significantly (136.3 +/- 4.2% and 138.5 +/- 10.3% of control). In conclusions, the herbal extract, F1 inhibited tibia and lumbar bone loss and did not cause uterine hypertrophy. However, 1-monolinolein, the main ingredient of the herbal extract, did not inhibit bone loss.
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PMID:Herbal extract prevents bone loss in ovariectomized rats. 1466 57

The specific pharmacological profile of the 19-norprogestin nomegestrol acetate (NOMAC) is, at least in part, defined by its pattern of binding affinities to the different steroid hormone receptors. In the present study, its affinity to the progesterone receptor (PgR), the androgen receptor (AR) and the estrogen receptor (ER) was re-evaluated and compared to those obtained for progesterone (P) and several progestins. The characteristics of binding to the PgR in rat uterus were determined and Ki were found to be roughly similar with 22.8 and 34.3 nM for NOMAC and P, respectively. The binding characteristics of 3H-NOMAC were also determined and compared to that of 3H-ORG2058 with Kd of 5 and 0.6 nM, respectively for rat uterus and 4 and 3 nM, respectively for human T47-D cells. Structure-affinity and -activity relationships were studied on a variety of compounds related to NOMAC in order to assess its specificity as a progestin. The effects of NOMAC on the binding of androgen to the AR were investigated, using rat ventral prostate as target model. Contrary to what was observed for MPA, the RBA of NOMAC was found to decline with time, showing anti-androgenic rather than androgenic potential, a result that was confirmed in vivo. Regarding the ER, since none of the progestins were able to compete with estrogen for binding in rat uterus as well as in Ishikawa cells, the induction of alkaline phosphatase activity (APase) was used as an estrogen-specific response. It confirmed the intrinsic estrogenicity of progestins derived from 19-nor-testosterone (19NT), norethisterone acetate (NETA), levonorgestrel (LNG) or norgestimate (NGM) and others. In contrast, all P and 19-norP derivatives remained inactive. Finally, to complete this overview of NOMAC at the sex steroid receptor levels, the lack of estrogenic or estrogenic-like activity was checked out in different in vitro models. Data from this study have demonstrated that NOMAC is a progestin that has greater steroid receptor selectivity compared to MPA or some other synthetic progestins. It may provide a better pharmacological profile than those progestins currently in use in HRT and OC.
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PMID:An overview of nomegestrol acetate selective receptor binding and lack of estrogenic action on hormone-dependent cancer cells. 1467 31

Antiresorptive therapy is usually given in a fixed dose, and we hypothesized that some patients receiving standard doses of hormone replacement therapy (HRT) might benefit from a higher dose, particularly if their bone turnover decreases after increasing the dose of HRT. Eighty-eight women who had been receiving standard-dose (0.625 mg/day) conjugated equine estrogens (CEE) for at least one year were randomized to take either standard-dose (0.625 mg/day, n = 36) or high-dose (1.25 mg/day, n = 52) therapy. Subjects with a uterus were allowed to take either 10 mg of medroxyprogesterone cyclically or 5 mg daily, according to personal preference. Bone Mineral Density (BMD) and biochemical markers of bone turnover were followed for 2 years. Mean bone turnover decreased significantly (-4.1% to -19.1%) after 6 months of high-dose CEE. Decreases in serum BSAP (bone-specific alkaline phosphatase) and serum or urine NTX ( N-terminal telopeptide crosslink of type I collagen) on high-dose therapy were not predictive of an improvement in BMD, but a decrease in serum CrossLaps did predict an improvement in BMD. Mean change in BMD in subjects with a significant decrease in serum CrossLaps at the anteroposterior spine was 3.1% +/- 3.9% versus 1.2% +/- 2.9% for subjects with no significant change in CrossLaps, P < 0.02. There was, however, a wide range of changes in BMD in patients with or without a significant change in CTX on high-dose HRT, making it impossible to predict an improvement in BMD based on an individual's changes in turnover. Measuring of bone density and bone turnover with better precision might be more successful in guiding individual dosing of antiresorptive therapy.
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PMID:Evaluation of ability of biochemical markers of bone turnover to predict a response to increased doses of HRT. 1496 Dec 15

Bone morphogenetic proteins (BMPs) play critical roles in cellular proliferation, differentiation, and programmed cell death in multiple tissues. An increasing body of recent evidence has suggested that classes of molecules collectively termed BMP antagonists play important roles for the local regulation of BMP actions by binding BMPs and neutralizing their activities. Uterine sensitization-associated gene-1 (USAG-1) was previously reported as a gene of unknown function, preferentially expressed in sensitized endometrium of the rat uterus. Here, we show that USAG-1 is abundantly expressed in the kidney and functions as a BMP antagonist. Recombinant USAG-1 binds directly to BMPs and antagonizes the BMP-mediated induction of alkaline phosphatase in C2C12 cells. USAG-1 also induces formation of secondary axis and/or hyperdorsalization when its mRNA is injected to Xenopus embryos. In the early stage of mouse embryogenesis, USAG-1 is expressed in the first and second branchial arches and in metanephros, while in later stages the expression is confined to renal tubules and ameloblasts of teeth. Postnatally, the expression is further restricted to distal tubules of kidney, in a pattern similar to the localization of BMP-7, which has been shown to be important in the development of kidney and preservation of adult renal functions under pathological stresses. Collectively, we suggest that USAG-1 is a BMP antagonist that interacts with BMP-7 in the developing and adult kidney.
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PMID:USAG-1: a bone morphogenetic protein antagonist abundantly expressed in the kidney. 1502 Feb 44

The purpose of this study was to examine whether whole aqueous black tea extract (BTE) prevents bone loss induced by ovarian hormone deficiency. Eighteen 95-100 days old female albino rats were randomly assigned to three treatment groups [sham -operated control (sham); bilaterally ovariectomized (ovx) and ovx + aqueous black tea extract (BTE) ] and sacrificed after 28 days. All animals were fed a standard laboratory diet with free access to deionized water except on days of urinary parameter studies when animals were given only calcium free deionized water during the entire 24 h period of urine collection. Body weight study revealed that rats in the ovx group had significantly higher final body weight than rats in the sham group. This higher final body weight was not observed in animals receiving BTE. The ovx group also had significantly higher abdominal fat mass and liver weight and significantly lower uterus, right kidney and left kidney weights than in other two groups. All these organ weight changes in ovx group also were not observed in animals receiving BTE. Results of urinary studies revealed that rats in the ovx group had significantly higher urinary excretion of calcium (Ca), phosphate, creatinine (Cr), calcium to creatinine (Ca:Cr) ratio (P< 0.001) and hydroxyproline (HPr) (P< 0.01) than rats in the sham group. Significant recovery of all these parameters were observed in animals receiving BTE. The ovx group also had significantly higher (P< 0.001) serum alkaline phosphatase (AP) and tartrate-resistant acid phosphatase (TRAP) activity than rats in the other two groups. These changes could not be seen in animals receiving BTE. Also, identical changes were seen in bone density experiments. Rats in the ovx group had significantly lower densities of the right femur (P<0.001), eighth thoracic rib (P< 0.001), eighth thoracic vertebra (P< 0.05), and fourth lumbar vertebra (P< 0.01) than rats in the sham group; and significant improvement in densities of these bones were seen in animals supplemented with BTE. Animals of ovx group also showed significant decrease in calcium and phosphate level in all these bones which could be regained significantly when these animals were supplemented with BTE. Our findings suggest that aqueous BTE may be effective in preventing bone loss due to ovarian hormone deficiency. Because serum activity of AP, TRAP and urinary loss of bone minerals (Ca and Phosphate) and also the organic components of bone (Cr and HPr) were significantly greater in the ovx group, compared to sham animals and ovx + BTE group. This confirms that ovariectomy enhances and BTE suppresses the rate of bone turnover. The density results of ovx + BTE group are significantly greater than rats in the ovx group, suggesting further that formation exceeded resorption. Detailed studies are underway to clarify the mechanism of this protective effect of BTE on hypogonadal bone loss.
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PMID:Evidence for a prospective anti-osteoporosis effect of black tea (Camellia Sinensis) extract in a bilaterally ovariectomized rat model. 1522 90

Efforts have been made to minimize the toxic effect caused by beryllium. Adult cyclic rats of Sprague Dawley strain were administered a bolus dose of 50mg/kg beryllium nitrate intramuscularly. The chelation therapy with glutathione (GSH), dimercapto propane sulfonic acid (DMPS)+ selenium (Se) and D-Penicillamine (DPA) + Se was given for 3 days followed by a rest of 1,3 and 7 days respectively. The results revealed a significant fall in the blood sugar level, serum alkaline phosphatase activity, serum proteins. A significant rise in the transaminases i.e. aspartate aminotranferase and alanine aminotranferase pattern is indicative of leakage of enzymes from liver resulting in alterations in the cell permeability. A rise in the hepatic lipid peroxidation activity is a direct indication of oxidative damage resulting in free radical generation. Results of the distribution studies by atomic absorption spectrophotometry reveal an increased concentration of beryllium in liver and kidney followed by lung and uterus. The relative ability of 3 chelating agents to act as antagonists for acute beryllium poisoning have been examined in liver, kidney, lungs and uterus. The appreciable change in the beryllium concentration in various organs is duration-dependent during the entire period being highly significant after 7 days rest. From the biochemical assays, and distribution studies it can be assumed that DPA+Se was the most effective therapeutic agent followed by DMPS+Se and GSH. Thus it can be concluded that DPA+Se is a better therapeutic agent as compared to DMPS+Se and GSH.
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PMID:Analysis of time-dependent recovery from beryllium toxicity following chelation therapy and antioxidant supplementation. 1557 30

Alteration in biochemical markers of bone turnover and bone mineral density (BMD) of whole body and isolated femur and tibia in relation to age, estrous cycle, pregnancy and lactation and suitability of use of rat as model for studies on pathophysiology of bone and therapeutic measures for its management were investigated. Immature rats (1, 1.5 and 2 month of age; weighing, respectively, 39.3+/-1.0, 67.8+/-2.4 and 87.2+/-5.2 g) exhibited high rate of bone turnover, as evidenced by high serum osteocalcin and alkaline phosphatase and urine calcium/creatinine ratio. However, their BMD (whole body or of isolated long bones) was below measurable levels. Marked increase in body weight at 3 months (185.5+/-5.2 g) was associated with low serum osteocalcin and alkaline phosphatase and urine calcium/creatinine ratio. Biochemical markers and BMD attained at puberty at 3 months were maintained until 36 month of age. No significant change in serum calcium was observed with increasing age or on any of the biomarkers during estrous cycle, and BMD of femur and tibia isolated during proestrus and diestrus stages was almost similar. Onset of pregnancy was associated with significant increase in serum total alkaline phosphatase and osteocalcin levels, but serum calcium, urine calcium/creatinine ratio or BMD of whole body or isolated long bones were not significantly different from that at proestrus stage. No marked change, except increase in body weight (P<0.05), was also evident in these parameters between days 5 and 19 of pregnancy, irrespective of number of implantations in the uterus. A significant decrease in BMD of isolated femur (neck and mid-shaft regions) was observed on days 5 and 21 of lactation as compared to that during pregnancy or diestrus/proestrus stages of estrous cycle; the decrease being almost similar in females lactating two or six young ones. BMD of isolated tibia (global and region proximal to tibio-fibular separation point), though generally lower than that during cycle and pregnancy, was statistically non-significant. However, clear evidence of occurrence of osteoporosis during lactation, with decrease in BMD of >2.5 x S.D. in isolated femur (global, neck and mid-shaft) as well as tibia (global) was observed only when BMD data was analysed on T-/Z-score basis. Serum biochemical markers of bone turnover, too, were significantly increased in comparison to cyclic rats. Findings demonstrate marked increase in body weight and bone turnover during first 3 months of age, direct correlation between peak bone mass and onset of puberty at 3 months of age and increase in bone resorption rate during lactation. Finding of the study while might suggests possible use of rat as useful model for studies on bone turnover rate during lactation and post-weaning periods and extrapolation of the result to the human situation, but not in relation to ageing.
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PMID:Attainment of peak bone mass and bone turnover rate in relation to estrous cycle, pregnancy and lactation in colony-bred Sprague-Dawley rats: suitability for studies on pathophysiology of bone and therapeutic measures for its management. 1587 7

Herbal Sambucus williamsii HANCE (SWH) is a folk medicine with a long history of safe use for treatment of bone fractures and joint diseases in China. The present study was designed to investigate if SWH extract could be used for treatment of postmenopausal osteoporosis. SWH extracts (30 or 60 mg/100 g body weight/d) were orally administrated to four-months-old ovariectomized (OVX) rats for 3 months. SWH extracts did not alter weight gain and uterus weight in OVX rats. SWH extracts significantly increased serum Ca levels (p<0.05, vs. OVX control group) as well as decreased urinary Ca excretion (p<0.01, vs. OVX control group) in OVX rats. The upregulation of serum alkaline phosphatase, serum osteocalcin as well as urinary deoxypyridinoline levels by OVX was suppressed by treatment with SWH extracts in rats (p<0.05, vs. OVX control group). SWH extract increased the stiffness of femur at both dosage (p<0.05, vs. OVX control group) and increased tibial bone mineral density at 60 mg/100 g body weight/d (p<0.05, vs. OVX control group) in OVX rats. Our results indicate that orally administrated SWH extracts can decrease urinary calcium excretion and bone turnover rate in OVX rats, resulting in positive effects on biomechanical strength of bone and bone mineral density. This study is the first to report that SWH could be considered as a potential candidate for management of postmenopausal osteoporosis. Then in vitro experiments were performed to determine the potential molecular mechanism of the anti-osteoporotic effect of SWH. Results suggested that chloroform fraction and ethyl acetate fraction of SWH can inhibit osteoclastogenesis osteoclast by modulating the expression of osteoprotegrin (OPG) and receptor activator of NF-kappaB ligand (RANKL) mRNA in osteoblastic UMR 106 cells. Both of them increased OPG mRNA and decreased RANKL mRNA expression, resulting in a dose-dependent increase in OPG/RANKL mRNA ratio (p<0.01, vs. vehicle-treated). Taken together, SWH treatment can effectively suppress the OVX-induced increase in bone turnover and its effects might be mediated by a decrease in osteoclastogenesis.
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PMID:Increase in bone mass and bone strength by Sambucus williamsii HANCE in ovariectomized rats. 1620 39


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