Absorption, bioavailability, and partner transfer of estradiol from a topical emulsion.

STUDY OBJECTIVE: To investigate the systemic absorption of estradiol in partners of postmenopausal women after making skin-to-skin contact with the application sites of estradiol topical emulsion. DESIGN: Open-label, nonrandomized clinical study. SETTING: Clinical study unit. SUBJECTS: Fourteen postmenopausal women and their male partners (mean +/- SD age 57.6+/-8.7 and 49.1+/-13.3 yrs, respectively). INTERVENTION: Women applied 1.74 g/day of estradiol topical emulsion (containing 2.5 mg estradiol/g) to each leg on 2 consecutive days. Their male partners were exposed to the application sites by mean of vigorous skin-to-skin contact at 2 and 8 hours after application. MEASUREMENTS AND MAIN RESULTS: Serum concentrations of estradiol, estrone, and estrone sulfate were measured in the female subjects and their male partners. The mean +/- SD estradiol level in the women at baseline was 2.9+/-1.5 pg/ml. Their average concentration (C(average)) increased from 15.3+/-14.8 pg/ml on the first day of treatment to 27.6+/-22.7 pg/ml on the second day. Among male partners, C(average) for serum estradiol increased from 17.0+/-4.3 pg/ml at baseline to 21.0+/-4.4 pg/ml on the second exposure day. Their geometric mean fold ratio for the area under the serum concentration-time curve from 0-24 hours was 1.25 (baseline vs after second exposure, p<0.0001). CONCLUSIONS: Estradiol was transferred to male partners by means of vigorous skin-to-skin contact at application sites. Although the increase in postexposure levels of estradiol was statistically significant, all levels were still below the upper limit of the normal range for men (45 pg/ml).

Effect of raloxifene on quality of life: a prospective study using the Utian Quality of Life (UQOL) Scale.

OBJECTIVE: The Utian Quality of Life Scale (UQOL) is a new questionnaire used to quantify patient perception of quality of life in postmenopausal women. The current study is the first to use the UQOL in ascertaining treatment effects on quality of life in postmenopausal women. DESIGN: This was a randomized, double-blind, placebo-controlled study of healthy postmenopausal women. Participants were randomized to raloxifene 60 mg/day or placebo. Participants completed the UQOL at baseline, at 3 months, and at the 6-month study endpoint. RESULTS: A total of 74 women (mean age, 55.6 years) were randomized. In the overall population, there were no significant changes from baseline to 6 months within or between treatment groups in any of the domains or total score, although raloxifene was associated with positive changes from baseline in the occupational (P = 0.093) and health (P = 0.055) domains. In women who completed the study, raloxifene was associated with a significant improvement from baseline in the occupational (P = 0.041) and health (P = 0.025) domains and in the total score (P = 0.044), whereas placebo had no effect. There were no statistically significant differences between raloxifene and placebo in any of the domains or total score. CONCLUSION: Although there were no treatment group differences, raloxifene was associated with an improvement from baseline in the occupational and health domains and in the overall score of the UQOL. Larger studies are needed using the UQOL as a primary endpoint to determine whether the positive effects of raloxifene on quality of life observed in this trial are real or a chance finding.

Modified quantitative association of official analytical chemists sporicidal test for liquid chemical germicides.

The Association of Official Analytical Chemists (AOAC) test for sporicidal activity of disinfectants (966.04) is used in the United States as the legal criteria for classifying a liquid as a chemical sterilant and also as the indicator of the highest level of disinfectant. This qualitative test contains procedures that may cause inaccurate results. A modified, quantitative version of the AOAC sporicidal test has been developed that uses a specified minimum number of spores (2.0 x 10(sup5)) of Bacillus subtilis or Clostridium sporogenes dried onto porcelain penicylinders. This modified test was validated with three commercial sterilant chemicals tested on three separate groups of spore-labeled cylinders.

Rapamycin (sirolimus, rapamune).

Rapamycin is a novel immunosuppressive agent that is undergoing clinical trials for use in allograft rejection therapy. This paper reviews its in-vitro biological properties, the current state of knowledge concerning its mechanism of action, and its therapeutic applications.

Identification of possible artifacts in the association of official analytical chemists sporicidal test.

Two laboratories tested four different brands of alkaline 2% glutaraldehyde sterilants by the Association of Official Analytical Chemists sporicidal test. Each laboratory found survival of Clostridium sporogenes spores on spore-labeled unglazed porcelain penicylinders (cylinders) to vary from test to test, and survival did not always correlate with increasing sterilant exposure time. These results were consistent with a theory that there may be random conditions within the test that prevent the sterilant from contacting all spores. Further studies indicated that the prior history of the unglazed porcelain cylinders and whether the C. sporogenes culture grown in egg-meat media had been processed (homogenized) to eliminate visible pieces of egg-meat media were important factors affecting the results and repeatability of this test.

Protective and restorative role of AS101 in combination with chemotherapy.

The immunomodulator AS101 has been found previously by us to stimulate the secretion of high levels of interleukin 1 and colony stimulating factor (CSF) in vitro, as well as the production of CSF in vivo in mice models. These cytokines are known to induce proliferation and differentiation of hematopoietic progenitor cells from the spleen and bone marrow (BM) and to protect mice from DNA-damaging agents. The present studies were designed to evaluate the effects of prolonged treatment with AS101 on myelopoiesis, BM cellularity, and CSF secretion in mice treated with a sublethal dose of cyclophosphamide (CYP) and on the survival of mice undergoing treatment with lethal doses of this compound. In this model, the hematopoietic progenitors were suppressed during the overbound phase of myelopoiesis resulting from the cytotoxic effects of CYP. This allowed the detection of a significant proliferative effect of AS101 in vivo on BM colony-forming units granulocyte-macrophage progenitor cells, BM cellularity, and the secretion of CSF. Moreover, AS101 protected these animals from the lethal effects of high doses of CYP. These protective effects were demonstrable only when AS101 was administered to mice prior to CYP treatment. The only exception was CSF secretion by spleen cells that had been reconstituted when AS101 was administered both prior to and following CYP treatment. AS101 was found to have a synergistic effect with CYP in the treatment of tumor-bearing mice, suggesting that the combination of these two modalities provides a more effective treatment of their tumors. These results strongly suggest an immunoregulatory role for AS101 in counteracting the chemotherapy-induced hematopoietic suppression as well as usefulness as adjunct treatment of cancer when used in combination with CYP.

Monocyte-derived macrophage and alveolar macrophage fibronectin production and cathepsin D activity.

Alveolar macrophages are thought to play an important role in ongoing tissue breakdown and repair processes in the normal lung. The secretion and regulation of cathepsin D (important for the final breakdown of collagen) and fibronectin (involved in the healing process) in human peripheral blood monocytes (PBM) and pulmonary alveolar macrophages (PAM) were investigated. Cathepsin D enzyme activity was measured by quantitating the TCA-soluble fragments of [3H]hemoglobin. Freshly isolated PBM contained less cell-associated cathepsin D activity than did freshly isolated PAM (314 +/- 35 micrograms/10(6) cells vs 381 +/- 35 micrograms/10(6) cells, respectively). After 7-10 days in culture, cell-associated enzyme levels in both PBM and PAM were significantly increased (P less than 0.001 for PBM; P less than 0.0001 for PAM). In addition, freshly isolated PAM secreted more cathepsin D than did freshly isolated PBM (5.8 +/- 3.2 micrograms/10(6) cells vs 0.83 +/- 0.83 micrograms/10(6) cells, P less than 0.02). In the presence of LPS (10 micrograms/ml), cell-associated cathepsin D was inhibited in both PBM and PAM. With the addition of gamma-IFN (500 U/ml), both cell-associated and secreted enzyme were increased in freshly isolated and 10-day-cultured PBM and PAM. In parallel studies, fibronectin secretion (by ELISA assay) in both PBM and PAM increased over time in culture. LPS had no effect on PBM or PAM secretion of human fibronectin while gamma-IFN increased PBM and PAM fibronectin levels. Thus, both macrophage cathepsin D activity and fibronectin secretion are increased by gamma-interferon while macrophage cathepsin D activity, but not fibronectin secretion, is decreased by LPS. These studies demonstrate that human macrophage cathepsin D activity is actively modulated by inflammatory mediators and that macrophage mediators of tissue breakdown and repair are not modulated synchronously.

[Prevention and repression in the control of food]. / Prevenzione e repressione nel controllo degli alimenti.

Prevention takes roots as in the medical culture as in the juridical tradition (with a significant reflex in the Italian Constitution). In the present study, these common purposes are considered for the solution of many problems with regard the quality and the hygiene of food. First of all, to avoid the risk caused by dangerous food and to reduce the repressive interventions, giving more space to the preventive action, a change of the general beginning of some laws is requested. Indeed, the modern penal doctrine rate the penalty as an effective means of "general prevention" only if the people think that the ethical foundation of the law is just, the technical basis of the matter is clear and the precepts are feasible. In the food matter the legislative clearness is hindered by a confused and incoherent stratification of the rules. On the other hand, the legitimacy of the laws can be contested when the rule opposes some general principles of justice and/or a balanced hierarchy of the values which should be ranged and defended by means of the law is missing. In those events the value of the penalty is disproportional to the real weight of the crime. In the requirements of foods the hierarchy of values is founded mainly on the nutritive quality, hygienic safety and market quotation. The combination of these parameters constitutes the so-called "pre-legislative scale of protected goods" which need to be inserted in the penal system.(ABSTRACT TRUNCATED AT 250 WORDS)