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PubMed1979

[Local corticoid therapy in pediatrics].

During 1978 I carried out a clinical trial in my pediatric practice with the new corticoid dermaticum Alfason, which contains the active substance hydrocortisone-17 abutyrate--an ester of hydrocortisone not previously used therapeutically. To begin with Alfason was given in an open trial to 100 children and later, because of the favourable results obtained, it was employed in another group of 100 children in a double-blind trial against a fluorinated corticoid, a substance which up to then I had most often prescribed. The results showed a good to very good effect in over 90% of the cases treated with either drug, there was no substance related statistical difference. According to the literature the ratio of success regarding side effects is particularly favourable for Alfason so that its use in the treatment of corticoid-requiring dermatoses in childhood can be recommended.

Administration, Topical↗
PubMed1981

A comparison of the effects of tixocortol pivalate (JO 1016), hydrocortisone acetate and beclomethasone dipropionate on collagen synthesis and degradation.

The effects of a corticosteroid substitute pregn-4-ene-3,20-dione-11 beta,17 alpha-dihydroxy-21-pivalate (tixocortol, JO 1016, Pivalone), hydrocortisone acetate and beclomethasone dipropionate on collagen metabolism in mouse calvariae were compared by histological and biochemical determination of collagen content, and by radio-assays of collagenase and collagenase inhibitor. Hydroxyproline assay revealed dose-related increases in collagen content/wet wt. tissue. These were greatest in explants treated with beclomethasone dipropionate, tixocortol pivalate being effective only at much higher concentrations than the other 2 drugs. Hydrocortisone acetate and beclomethasone dipropionate stimulated collagenase production at the lowest levels tested whereas tixocortol pivalate was only slightly stimulatory at the highest treatment level. These results suggest that in clinical use tixocortol pivalate would be much less likely than hydrocortisone acetate or beclomethasone dipropionate to cause degenerative changes in connective tissue.

Administration, Topical↗
PubMed1981

Pharmacological study of a new anti-inflammatory steroid, tixocortol pivalate (JO 1016).

Some pharmacological activities of pregn-4-ene-3,20-dione-21-thiol-11 beta,17 alpha-dihydroxy-21-pivalate (tixocortol pivalate, JO 1016 Pivalone), a new steroidal anti-inflammatory compound, are described. The anti-inflammatory activity of tixocortol pivalate has been clearly demonstrated in various tests using adrenalectomised and intact animals. Of particular interest is the dissociation of its local and systemic activities. Comparison with hydrocortisone acetate indicates a similar or greater anti-inflammatory activity, by either the local or topical routes, but tixocortol pivalate is between 60 and 300 times less active than hydrocortisone acetate after oral or subcutaneous administration. Glucocorticoid activity was only detected at very high oral doses of tixocortol pivalate and the highest tested subcutaneous dose (300 mg/kg) failed to induce significant activity. Hydrocortisone acetate exerted glucocorticoid effects at much lower doses. It is possible therefore the local or topical use of tixocortol pivalate in therapy may not cause the unwanted side effects of many of the corticosteroids in current use.

Administration, Oral↗
PubMed1981

A comparison of the effects of tixocortol pivalate (JO 1016), beclomethasone dipropionate and hydrocortisone acetate on the activation of lymphocytes.

A comparative study was made of the effects of hydrocortisone acetate, beclomethasone dipropionate and a corticosteroid substitute (pregn-4-ene-3,20-dione-21-thiol-11 beta,17 alpha-dihydroxy-21-pivalate, tixocortol pivalate, JO 1016, Pivalone) on lymphocyte activation. The response measured in vivo was the production of heamagglutinating antibody by mice in response to immunization with sheep erythrocytes. The in vitro response tested was the blastocytic transformation of T cells in mixed lymphocyte culture. All three compounds suppressed T cell activation in vitro. Tixocortol pivalate however, was non-toxic and non-immunosuppressive when administered to mice, in contrast to hydrocortisone acetate and beclomethasone dipropionate, which were toxic and immuno-suppressive at the highest dose levels tested. These results indicated that tixocortol pivalate would, by virtue of its low toxicity and absence of general immunosuppression, have potential advantages over both hydrocortisone acetate and beclomethasone dipropionate in the topical treatment of allergic conditions of mucous membranes.

Administration, Topical↗
PubMed1981

A comparison of the effects of tixocortol pivalate (JO 1016), hydrocortisone acetate and beclomethasone dipropionate on the phagocytosis and lysis of microorganisms by alveolar macrophages.

A comparison was made of the ability of guinea pig alveolar macrophages, which had been pretreated with hydrocortisone acetate, beclomethasone dipropionate or a corticosteroid substitute pregn-4-ene-3,20-dione-21-thiol-11 beta,17 alpha-dihydroxy-21-pivalate (tixocortol pivalate, JO 1016, Pivalone), to phagocytose and lyse Staphylococcus aureus or Candida albicans. The three drugs had different patterns of effect on phagocytosis and lysis. Hydrocortisone acetate had little effect on the phagocytosis of Staph. aureus at any dose level tested, but the two higher concentrations slightly inhibited intracellular lysis; phagocytosis of C. albicans was inhibited initially but increased at 5 h. Both beclomethasone dipropionate and tixocortol pivalate caused an initial stimulation of phagocytosis and lysis of Staph. aureus. Ingestion of C. albicans was increased in macrophages pretreated with beclomethasone dipropionate, but their fungicidal activity was unchanged. Pretreatment with tixocortol pivalate stimulated the initial phagocytosis of C. albicans but continued uptake on prolonged incubation was inhibited. Lysis of the ingested organisms was not markedly affected. Since the production of any effect on the phagocytic and lytic activity of alveolar macrophages required much higher levels of tixocortol pivalate than of either of the other two drugs, it is suggested that in clinical use correspondingly higher doses of tixocortol pivalate could be given without danger of affecting either phagocytic activity or the immune response.

Administration, Topical↗
PubMedDate not supplied

Subclinical changes in luteal function in cynomolgus monkeys with moderate blood lead levels.

The objective of the present study was to investigate luteal function in cynomolgus monkeys (n = 32), aged 15-20 years with blood lead levels (BLLs) in the range of < 3.0 micrograms dl-1 (control, n = 20), 10-15 micrograms dl-1 (low, n = 7) and 25-30 micrograms dl-1 (moderate, n = 5). Sampling was performed daily beginning with day 10 of the menstrual cycle and concluding on the first day of the subsequent menstrual cycle. Circulating levels of oestradiol (E2), progesterone (P4) and 20 alpha-hydroxyprogesterone (20-OHP) were normalized to the day of the ovulatory E2 surge. The area under the concentration curve (AUC) for P4 was significantly lower in monkeys with moderate BLLs compared to the control group (P = 0.04). The number of days for which circulating levels of P4 were greater than 1.0 ng ml-1 were also significantly fewer (P = 0.03) in monkeys with moderate BLLs compared to controls. There was no statistical evidence of a lead effect on circulating levels of E2, 20-OHP or menstrual cycle characteristics. These data suggest that chronic lead exposure suppresses corpora luteal production of P4 in the monkey at circulating BLLs lower than previously reported and relevant to humans with occupational exposure to lead.

Algestone↗
PubMed2005

Combination injectable contraceptives for contraception.

BACKGROUND: Combination injectable contraceptives provide a highly effective, reversible method of preventing pregnancy, and they do not require daily administration or use at the time of coitus. Although they are used in many countries, their acceptability could be limited by method characteristics, such as the need to obtain a monthly injection or bleeding pattern changes. OBJECTIVES: To assess the contraceptive efficacy, bleeding patterns, discontinuation, user preferences, and side effects of combination injectable contraceptives. SEARCH STRATEGY: We searched computerized databases for randomized controlled trials of combination injectable contraceptives. SELECTION CRITERIA: Randomized controlled trials reported in any language were eligible if they compared a combination injectable with any other contraceptive method (e.g., a second combination injectable contraceptive, progestin-only injectable contraceptive, other hormonal contraceptive or barrier method) or placebo. We limited the review to currently marketed combination injectable contraceptives. DATA COLLECTION AND ANALYSIS: The primary reviewer evaluated all titles and abstracts from the literature searches to determine their eligibility. Two reviewers independently extracted data from the eligible trials. Data on contraceptive efficacy, bleeding patterns, continuation, and side effects were entered and analyzed with RevMan 4.2. MAIN RESULTS: Combination injectable contraceptives include depot medroxyprogesterone acetate (DMPA) 25 mg plus estradiol cypionate (E(2)C) 5 mg, as well as norethisterone enanthate (NET-EN) 50 mg plus estradiol valerate (E(2)V) 5 mg. These combination injectable contraceptives resulted in lower rates of early study discontinuation due to amenorrhea or other bleeding problems, but had higher rates of discontinuation due to other reasons than the progestin-only comparison contraceptives. Studies comparing two combination injectable contraceptives found that NET-EN 50 mg plus E(2)V 5 mg resulted in less overall early discontinuation and less discontinuation due to amenorrhea or prolonged bleeding than DMPA 25 mg plus E(2)C 5 mg. However, these differences were not detected in all trials making this comparison. The NET-EN plus E(2)V group also had more cyclical (regular) bleeding and fewer prolonged bleeding reference periods than the DMPA plus E(2)C group. The groups did not differ in their amenorrhea rates. AUTHORS' CONCLUSIONS: While discontinuation rates can be viewed as a measure of method acceptability, the findings should be interpreted with caution since discontinuation rates are dependent on many other factors. Future research should be directed toward interventions to improve the acceptability of combination injectable contraceptives, such as providing injections in settings more convenient than clinical sites, methods for women to administer their own injections, and counseling about possible bleeding pattern changes.

Algestone↗
PubMed1993

Plasma membrane cholesterol is utilized as steroidogenic substrate in Y-1 mouse adrenal tumor cells and normal sheep adrenal cells.

Previous studies from this laboratory indicate that plasma membrane cholesterol acts as an important source of steroidogenic substrate for MA-10 Leydig tumor cells. The present studies were designed to generalize these findings to other steroidogenic cells and to another species. Studies were performed using the Y-1 murine adrenal tumor cell line and primary cultures of sheep adrenocortical cells. Treating Y-1 cells with the acyl coenzyme A:cholesterol acyltransferase inhibitor, 58-035, caused cellular cholesteryl ester depletion and rendered more apparent the effect of dibutyryl-cAMP to cause cellular free cholesterol depletion. Radioactive 20 alpha-dihydroprogesterone was synthesized by Y-1 cells that had been plasma membrane-labeled with [3H]-cholesterol. Primary sheep adrenal cultures that had been cholesteryl ester-depleted also demonstrated cellular free cholesterol depletion after stimulation with dibutyryl cAMP. Plasma membrane label was converted to steroid hormones in these cells as well. Taken together, these data indicate that the use of plasma cholesterol is not restricted to the MA-10 cells. The present data indicate that both neoplastic mouse adrenal tumor cells and normal sheep adrenal cells utilize plasma membrane cholesterol.

Adrenal Gland Neoplasms↗