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PubMed1992

Control of predialytic hyperphosphatemia by oral calcium acetate and calcium carbonate. Comparable efficacy for half the dose of elemental calcium given as acetate without lower incidence of hypercalcemia.

Since Mai et al. found, with the intestinal lavage technique, that the same dose of elemental calcium given as acetate (Ca Ac) complexed in the gut of uremic patients twice as much phosphate as calcium carbonate (CaCO3) while inducing a rather low calcium absorption, we wanted to see if half the dose of elemental calcium given as Ca Ac could control, on medium term, the predialysis plasma phosphate as well as CaCO3 while inducing less frequent hypercalcemia. This was evaluated in a cross-over study of 3 periods of 10 weeks according to the sequence Ca Ac, CaCO3 and Ca Ac, in 12 compliant patients on chronic dialysis previously treated by CaCO3. Because of poor tolerance of Ca Ac during the first period, 4 patients were excluded and the results were assessed only on the 8 patients who completed the study. For half the doses of elemental calcium (620 +/- 250 mg versus 1,310 +/- 560 mg versus 710 +/- 200 mg/day), Ca Ac allowed the same control of predialytic hyperphosphatemia (1.67 +/- 0.34; 1.74 +/- 0.32; 1.75 +/- 0.38) with paradoxically comparable normal mean plasma calcium concentration (2.61 +/- 0.14; 2.56 +/- 0.13; 2.55 +/- 0.14 mmol/l). Plasma alkaline phosphatases and intact PTH concentrations remained also stable during the 3 periods. The frequency of hypercalcemia greater than 2.75 mmol/l (12; 9; 20%) and of hyperphosphatemia greater than 2 mmol/l (17; 22; 27%) were comparable with the 2 treatments. In conclusion, Ca Ac controls predialytic hyperphosphatemia as efficiently as CaCO3 for half the dose of elemental calcium without, however, decreasing the frequency of hypercalcemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

PubMed2000

[Comparative study between estradiol valerate combined with cyproterone acetate, and conjugated equine estrogens combined with medroxyprogesterone acetate as hormone replacement therapy in climacteric].

OBJECTIVE: To compare the effectiveness in the control of climacteric symptoms, the tolerability and the uterine bleeding pattern between two types of hormone replacement therapy. MATERIAL AND METHODS: 81 postmenopausal women between 40 and 60 years age with vasomotor symptoms were studied. Randomly it was administered: I. Conjugated equine estrogens (CEE)-Medroxyprogesterone acetate (MPA): 21 tablets with 0.625 mg of CEE and 10 tablets with 5 mg of MPA which were taken with the last ten tablets of CEE in each cycle (n = 3 7). II. E2V-CPA: 11 tablets with 2 mg of E2V and 10 tablets with 2 mg of E2V and 1 mg of CPA (n = 44). Each cycle comprised 28 days. The treatments were compared with squared Chi and Mann-Whitney U test. RESULTS: The hot flushes presence was significantly greater in the group with CEE-MPA (p < 0.03). Severe throbs at the end of the study had a trend to be more frequent in the group with EC-MPA (p < 0.06). At the end of the study there was a greater frequency of breast tenderness in the group with CEE-MPA (P = 0.009). CONCLUSIONS: Both treatments have good effectiveness, tolerability and same bleeding pattern. Only the frequency of hot flushes, the presence of severe throbs and breast tenderness were lower in the group with E2V-CPA, that makes this preparation an option that can have a better acceptance by the women.

Adult↗

PubMed1981

Cyproterone acetate, testosterone, LH, FSH, and prolactin levels in plasma after intramuscular application of cyproterone acetate in patients with prostatic cancer.

Five patients with prostatic carcinoma (stages T3N0M0) were injected intramuscularly with 300 mg of cyproterone acetate (CPA) (Androcur-Depot) at weekly intervals. The concentrations of CPA, testosterone, LH, FSH, and prolactin in plasma after the first, third, and fifth injection were measured by specific radioimmunoassays. After five injections of Androcur-Depot, CPA levels were slightly higher than in previous determinations, suggesting that a balance between active substance release from the depot and excretion could be achieved after eight to twelve injections, with only slightly higher levels of active substance attained. Testosterone levels clearly were reduced after the first injection of CPA, but the lowest values were registered only after three injections. Plasma concentrations of FSH and LH were slightly diminished, whereas the prolactin level increased after CPA therapy.

Cyproterone↗

PubMed1988

Hormonotherapy of meningiomas with medroxyprogesterone acetate. Immunohistochemical demonstration of the effect of medroxyprogesterone acetate on growth fractions of meningioma cells using the monoclonal antibody Ki-67.

The effect of medroxyprogesterone acetate (MPA) on growth fractions of ex vivo meningiomas is demonstrated in using the Ki-67 monoclonal antibody in three cases of meningiomas operated on in two stages and in meningioma specimens from a group of eight patients operated on in one single stage after MPA therapy. Growth fractions in samples from five meningioma patients not treated with MPA were determined for comparison. In the three cases of two-stage operation of the tumors, the percentage of Ki-67-positive cells in meningioma tissue was lower by a factor of 6, 5, and 3, respectively, after MPA therapy. In meningioma specimens from patients receiving no MPA therapy, Ki-67-positive cells were present in 1.02 +/- 0.48%; in samples from MPA-treated tumors the percentage of Ki-67-positive cells was 0.41 +/- 0.40 (different at p less than 0.02 [Wilcoxon's test]). In comparison to our previously published data on untreated meningiomas analyzed for progesterone receptors (PR), MPA significantly reduced the PR activity. There was no obvious correlation between PR activity and potential suppression of the tumor growth fraction. It is concluded that MPA is attractive because it reduces the growth fractions of most meningiomas and might be suitable for adjuvant hormonotherapy.

Antibodies, Monoclonal↗

PubMed1988

Angiogenic activity of rat mammary carcinomas induced by 7,12-dimethylbenz[a]anthracene and its inhibition by medroxyprogesterone acetate: possible involvement of antiangiogenic action of medroxyprogesterone acetate in its tumor growth inhibition.

The significant inhibitory activity of medroxyprogesterone acetate (MPA) against mammary tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) was confirmed in female Sprague-Dawley (SD) rats, and was found to be independent of the estrogen receptor (ER) level. To facilitate elucidation of the mechanism underlying the antitumor activity of MPA against the rat mammary tumors (RMTs) regardless of ER status, the present study was conducted to determine whether or not a DMBA-induced RMT had the capacity to elicit angiogenic activity on tissue implantation into a rabbit cornea, and, if so, to determine whether or not the angiogenic activity of the RMT was inhibited by MPA. The RMTs obtained were classified into two groups based on the ER level; ER-positive and -negative groups. Both groups exhibited relatively strong angiogenic activity, the activity of the ER-negative group being significantly higher than that of the ER-positive one. The angiogenesis produced by both groups of RMTs was significantly inhibited by MPA, as judged from the results of the rabbit cornea assay. Similarly, MPA almost entirely suppressed not only the angiogenesis but also the growth of rabbit VX2 tumors without ER, included as a positive control as to the induction of angiogenic activity. In vitro experiments using neoplastic epithelioid RMT-1 and -2 cells cloned from DMBA-induced RMTs demonstrated that MPA had little or no suppressive effect on the growth of these epithelial cells. These results suggest that the inhibitory action of MPA toward the angiogenic activity of RMTs, at least in part, involves its antitumor activity toward the RMTs.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2006

Glatiramer acetate-specific human CD8(+) T cells: increased IL-4 production in multiple sclerosis is reduced by glatiramer acetate treatment.

Glatiramer acetate (GA) is an approved drug for therapy of relapsing remitting MS that acts as a T cell antigen. Here, we report the cloning of HLA restricted, GA-specific human CD8(+) T cells. In addition, we analyzed the cytokine profile of GA-reactive CD8(+) T cell lines. Unexpectedly, IL-4 was increased in untreated MS patients as compared to healthy individuals (p<0.001). In GA-treated patients, however, IL-4 (p<0.001), IL-10 (p<0.001) and TNF-alpha (p<0.001) were decreased. Thus, while GA is known to induce a TH2 bias in CD4(+) T cells, we detected a distinct pattern in GA-reactive CD8(+) T cells.

Adult↗

PubMed1978

(Acylaryloxy)acetic acid diuretics. 2. (2-Alkyl-2-aryl-1-oxo-5-indanyloxy)acetic acids.

The introduction of an aryl group at the 2 position of the uricosuric diuretics, (1-oxo-2-alkyl-5-indanyloxy)acetic acids, provided compounds with markedly increased potency over their monosubstituted precursors. These compounds were synthesized either by arylation of the corresponding 2-alkyl-5-methoxy-1-indanones with diaryliodonium salts or by alkylation of the 2-aryl-5-methoxy-1-indanones which were cleaved to the corresponding phenols and then converted to the desired oxyacetic acids. Systematic structural variation of the 2-arylindanyloxyacetic acids provided aryl-substituted compounds with varying degrees of uricosuric and diuretic activity.

Acetates↗

PubMed1976

(Vinylaryloxy)acetic acids. A new class of diuretic agents. 4. Various ((2-substituted and 2,2-disubstituted vinyl)aryloxy)acetic acids.

A variety of [(2-substituted and 2,2-disubstituted vinyl)aryloxy]acetic acids was synthesized in which the substituents were primarily electron-withdrawing groups. These compounds were tested in dogs for their saluretic and diuretic properties. Many of the compounds exhibited significant activity; however, they were generally less potent than those reported in the three earlier papers in this series.

Acetates↗

PubMed2006

4,6-O-[1-cyano-2-(2-iodophenyl)ethylidene] acetals. improved second-generation acetals for the stereoselective formation of beta-D-mannopyranosides and regioselective reductive radical fragmentation to beta-D-rhamnopyranosides. scope and limitations.

The [1-cyano-2-(2-iodophenyl)]ethylidene group is introduced as an acetal-protecting group for carbohydrate thioglycoside donors. The group is easily introduced under mild conditions, over short reaction times, and in the presence of a wide variety of other protecting groups by the reaction of the 4,6-diol with triethyl (2-iodophenyl)orthoacetate and camphorsulfonic acid, followed by trimethylsilyl cyanide and boron trifluoride etherate. The new protecting group conveys strong beta-selectivity with thiomannoside donors and undergoes a tin-mediated radical fragmentation to provide high yields of the synthetically challenging beta-rhamnopyranosides. The method is also applicable to the glucopyranosides when high alpha-selectivity is observed in the coupling reaction and alpha-quinovosides are formed selectively in the radical fragmentation step. In the galactopyranoside series, beta-glycosides are formed selectively on coupling to donors protected by the new system, but the radical fragmentation is unselective and gives mixtures of the 4- and 6-deoxy products. Variable-temperature NMR studies for the glycosylation step, which helped define an optimal protocol, are described.

Acetals↗

PubMed1986

Synergistic potentiation of 5-hydroxytryptamine secretion by platelet agonists and phorbol myristate acetate despite inhibition of agonist-induced arachidonate/thromboxane and beta-thromboglobulin release and Ca2+ mobilization by phorbol myristate acetate.

Previous studies have demonstrated an inhibition of agonist-induced inositol phospholipid breakdown and intracellular Ca2+ ([Ca2+]i) mobilization by phorbol esters in platelets. In this study, we have examined the effect of phorbol 12-myristate 13-acetate (PMA) on agonist-induced granule secretion and correlated it with agonist-induced [Ca2+]i mobilization, arachidonate and thromboxane (Tx) release in human platelets. With increasing times of incubation with PMA (10 s-5 min), the rise in [Ca2+]i induced by thrombin and the TxA2 mimetic, U46619, was increasingly inhibited (90-100% with 5 min incubation) and, correlating with this, thrombin-induced [3H]arachidonate, TxB2 and beta-thromboglobulin (beta TG) release were also inhibited. In addition, the conversion of exogenously added arachidonate to TxB2 was inhibited (50-80%) by a 10 s-5 min pretreatment with PMA. However, secretion of 5-hydroxy[14C]tryptamine (5HT) induced by thrombin or U46619 was not inhibited by 10 s-2 min incubations with PMA and, on the contrary, with low agonist concentrations, was potentiated by PMA in the absence of a significant rise in [Ca2+]i or endogenous Tx formation, to levels significantly greater than or equal to the sum of that obtained when agonist and PMA were added separately. With longer times of incubation with PMA (5 min), these synergistic effects became less pronounced as inhibitory effects of PMA on agonist-induced [14C]5HT secretion became apparent. The results indicate that, while PMA may cause an inhibition of agonist-induced [Ca2+]i mobilization resulting in an inhibition of agonist-induced arachidonate, TxB2 and beta TG release, its effects on agonist-induced 5HT secretion may be complicated by [Ca2+]i-independent synergistic effects of agonist and PMA.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed2003

Sequential transarterial chemoembolization and percutaneous acetic acid injection therapy versus repeated percutaneous acetic acid injection for unresectable hepatocellular carcinoma: a prospective study.

BACKGROUND: Transarterial chemoembolization (TACE) and percutaneous acetic acid injection (PAI) are effective treatments for hepatocellular carcinoma (HCC). We have conducted a prospective study to compare the efficacy of sequential TACE and PAI (TACE-PAI) versus repeated PAI therapy for HCC. PATIENTS AND METHODS: A total of 108 HCC patients with tumor size </=5 cm were enrolled. Fifty-three patients were treated with TACE-PAI and 55 patients were treated with PAI alone. RESULTS: Objective responses were achieved in 72 of 80 nodules (90%) in the TACE-PAI group compared with 51 of 62 nodules (82%) in the PAI group (P = 0.217) during 24 +/- 10 months of follow-up. Patients in the TACE-PAI group had a significantly lower cumulative tumor recurrence rate from the treated nodule (P = 0.004) or newly developed tumor elsewhere in liver (P = 0.010). Complete tumor necrosis in large (3-5 cm) HCCs was more frequently encountered in the TACE-PAI group (64% versus 37%; P = 0.034). There was no significant survival difference between the two groups with small (</=3 cm) HCC (P = 0.569), whereas PAI therapy was an independent poor prognostic predictor [relative risk 3.0 (95% confidence interval 1.2-7.6); P = 0.017] in the large HCC group. CONCLUSIONS: Sequential therapy with TACE and PAI is superior to repeated PAI alone for patients with large HCC.

Acetic Acid↗

PubMed2005

Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain.

BACKGROUND: A clinical study compared efficacy and safety of depot medroxyprogesterone acetate (DMPA) with leuprolide for endometriosis-associated pain. METHODS: This multicentre, 18 month, evaluator-blinded, comparator-controlled trial randomized 300 women with laparoscopically diagnosed endometriosis to 6 month treatment with subcutaneous injection of 104 mg/0.65 ml DMPA (DMPA-SC 104) every 3 months or leuprolide (3.75 mg monthly or 11.25 mg every 3 months), with 12 months post-treatment follow-up. Endpoints included patient response to treatment in five signs/symptoms (dysmenorrhoea, dyspareunia, pelvic pain, pelvic tenderness, induration) and changes in bone mineral density (BMD) and productivity at 6 and 18 months. RESULTS: DMPA-SC 104 and leuprolide produced equivalent (P < 0.02) reductions in at least four pain categories and significant (P < 0.001) improvements in composite score at months 6 and 18. At month 6, reductions in total hip and lumbar spine BMD were significantly less (P < 0.001) with DMPA-SC 104 versus leuprolide. BMD returned to pre-treatment levels 12 months post-treatment in the DMPA-SC 104 but not the leuprolide group. Total productivity also significantly (P < or = 0.05) improved in both groups at 6 and 18 months. CONCLUSIONS: DMPA-SC 104 reduces endometriosis-associated pain as effectively as leuprolide and improves productivity with significantly less BMD decline.

Administration, Cutaneous↗

PubMedDate not supplied

Cyproterone acetate: I. Microquantity releasing device of cyproterone acetate and its failure in inducing functional sterility in male rats.

Prasad and his coworkers emphasized that microquantities of cyproterone acetate (CPA) when continuously available developed functional sterility in male rats by interfering the epididymal physiology. In our experimental rats either 2 or 3 capsules containing CPA as per the specification of Prasad were implanted subcutaneously and left for 300 and 250 days, respectively. Fertility test was made every month and it was observed that all the experimental animals were able to impregnate female rats throughout the experiment. Excepting the epididymis the weight of testes and other accessory glands did not differ from the controls in the animals which had 2 CPA capsules for 300 days; On the other hand, the animals which received 3 CPA capsules for 250 days showed significant reduction in weight of all the acessory glands including the testes.

Animals↗

PubMed1986

Synovial fluid and plasma kinetics of methylprednisolone and methylprednisolone acetate in horses following intra-articular administration of methylprednisolone acetate.

Synovial fluid and plasma kinetics of methylprednisolone acetate (MPA) and methylprednisolone (MP) after a single intra-articular administration of MPA at a therapeutic dose (111 mg in toto) was measured in five horses. MPA was detected in synovial fluid for two to six days post injection and MP, which results from synovial MPA hydrolysis, was present in pharmacologically significant concentrations for 4.8 to 39 days, depending on the horse. MPA synovial concentration was maximal (289 +/- 284 micrograms/ml) at the first sampling time (2 h after administration) and MP synovial concentration was maximal (from 58.9 to 379.5 micrograms/ml) at the first or second sampling time (2 to 10 h after administration). Thereafter, both MP and MPA declined rapidly. From time of administration to about five days later, MP synovial fluid concentration fell progressively with a half-time of 9.95 h. Subsequently, the MP synovial fluid concentration decreased more slowly with an apparent half-time of 115 h. During the first 24 h following MPA administration, trace amounts of MP (less than 5 ng/ml) were detected in plasma. Plasma hydrocortisone levels were depressed for three to four days after administration but adrenal responsiveness to adrenocorticotrophic hormone tests remained unaffected.

Adrenal Glands↗

PubMed2001

Characterization of acetic acid bacteria in traditional acetic acid fermentation of rice vinegar (komesu) and unpolished rice vinegar (kurosu) produced in Japan.

Bacterial strains were isolated from samples of Japanese rice vinegar (komesu) and unpolished rice vinegar (kurosu) fermented by the traditional static method. Fermentations have never been inoculated with a pure culture since they were started in 1907. A total of 178 isolates were divided into groups A and B on the basis of enterobacterial repetitive intergenic consensus-PCR and random amplified polymorphic DNA fingerprinting analyses. The 16S ribosomal DNA sequences of strains belonging to each group showed similarities of more than 99% with Acetobacter pasteurianus. Group A strains overwhelmingly dominated all stages of fermentation of both types of vinegar. Our results indicate that appropriate strains of acetic acid bacteria have spontaneously established almost pure cultures during nearly a century of komesu and kurosu fermentation.

Acetic Acid↗

PubMed1992

Skeletal muscle protein metabolism and serum growth hormone, insulin, and cortisol concentrations in growing steers implanted with estradiol-17 beta, trenbolone acetate, or estradiol-17 beta plus trenbolone acetate.

Skeletal muscle protein degradation, measured by urinary N tau-methylhistidine excretion, and circulating concentrations of growth hormone (GH), insulin (INS), and cortisol (CT) were monitored in steers before and after implantation with estradiol-17 beta (E2; 24 mg) and trenbolone acetate (TBA; 300 mg). Yearling crossbred steers (n = 43) were randomly assigned to four treatment groups in a 2 x 2 factorial arrangement: nonimplanted controls (C); TBA; E2; and TBA plus E2 (TBA+E2). A subgroup (Block 1) of 16 steers was bled on d -12, 31, and 72 after implanting. Deposition of skeletal muscle protein was markedly increased (P less than .001) by E2 and TBA+E2 treatment. This response occurred mainly within the first 40 d after implantation and declined (P less than .001) in concert with decreasing (P less than .01) concentration of serum E2. Anabolic steroid treatment did not affect the rate of skeletal muscle protein breakdown. There was no apparent relationship between reduced serum CT concentration (linear effect; P less than .01) in TBA-treated steers and skeletal muscle protein degradation rate. Blood concentration and pulse activity of INS were not affected by anabolic steroid administration. Both TBA- and TBA+E2-implanted steers displayed a linear decrease (P less than .05) in serum GH concentration over time, which was similar to C. Lowered mean GH concentration resulted from a reduction (TBA main effect; P less than .05) in pulse amplitude of GH. Unlike TBA, TBA+E2, and C, only E2 maintained serum GH concentrations over time. Although increased muscle protein deposition was evident in TBA+E2-treated steers, an obvious causal relationship between this response and circulating GH, INS, and CT was not revealed. These results do not support the concept that combined androgenic agent and estrogen administration effectively reduce bovine muscle protein degradation by static modulation of circulating endogenous anabolic and antianabolic hormones.

Anabolic Agents↗

PubMed1988

[The medroxyprogesterone acetate serum level following various medroxyprogesterone acetate dose schedules in gynecologic oncology].

Medroxyprogesterone acetate (MPA) is used as an adjuvant hormonal medication in patients with different kinds of carcinomas. Since adequate serum levels are thought to be essential we determined the individual, postoperative MPA levels in 36 patients with endometrial carcinoma over a period of 12 weeks. The patients received either an oral dose of 3 X 100 mg MPA or a weekly changing scheme with 2 X 10 mg Tamoxifen and 3 X 100 mg MPA. An additional small group of 4 patients with ovarian carcinoma was enrolled receiving an oral dose of 1000 mg MPA daily. The peripheral serum levels of MPA exhibit enormous inter- and intraindividuell variations and only the high dosage schemes yield levels above 90 ng/ml which are claimed necessary by some authors. The cortisol concentration measured at the same time were within the normal range and did not correlate with the MPA values.

Antineoplastic Agents↗

PubMed1987

Isolation of 12-O-tetradecanoylphorbol-13-acetate-resistant mutants of a macrophage-like cell line: evidence for induction by 12-O-tetradecanoylphorbol-13-acetate of a non-colony-stimulating growth factor.

There has been much recent interest in the role of a calcium-dependent, phospholipid-dependent protein kinase (PKC) in regulation of macrophage function and growth. In order to better define the role of PKC in these processes we have developed mutants of the RAW264 macrophage-like cell line that are resistant to the growth-inhibiting effects of 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent stimulator of PKC activity. Concentrations of TPA of 10(-7) M or greater resulted in more than 90% inhibition of growth of RAW264 cells and were used to select for TPA-response mutants. Ultraviolet mutagenesis of 10(6) cells and growth selection under inhibitory TPA concentrations yielded 12 colonies. Two isolated lines (M11 and M12) were studied in detail. Neither cell line was deficient in, nor appeared to have an altered PKC, based on enzymatic activity in response to TPA or diacylglycerol. Both cell lines could grow in the presence of 10(-6) M TPA. After removal of TPA, mutant M11 continued to grow while M12 died. Growth of M12 cells was TPA concentration dependent. Flow cytometric analysis of the DNA content of M12 cells in the absence of TPA indicated that cell growth was arrested in G0 or G1. This was interpreted as indicating that TPA acted as a growth factor inducing cells to enter the cell cycle. M12 cells could also grow in L-cell-conditioned medium containing colony-stimulating factor-1 (CSF-1), the normal growth factor for cells of the macrophage lineage. After subcloning M12 cells, it was found that several subclones of M12 did not grow in response to TPA but did grow well in L-cell medium. These cells would grow in medium conditioned by the exposure of TPA-responsive subclones to TPA. Bone marrow culture cells also grew in the conditioned medium. The growth factors produced by the TPA responsive subclones were not neutralized by anti-CSF-1 antiserum. These results suggest that TPA may not directly induce the growth of M12 cells or the formation of colonies of bone marrow cells, but instead may act through the induction of a non-CSF-1 growth factor. These mutants can be used as tools for future studies on the role of PKC in the regulation of macrophage growth.

Animals↗