The Oregon depo-Provera Prograxm: A Five-Year Follow-Up

In 1999, the Oregon State Legislature, concerned about the risk certain sexual offenders might pose to their communities upon release from prison, enacted House Bill 2500. This bill required selected offenders to be evaluated prior to their release to determine whether medical treatment with medroxyprogesterone acetate (MPA), also known by its trade name of depo-Provera, was indicated to reduce their risk. The present study reviewed the first 275 men to be evaluated under this program from the years 2000 through 2004. Data were collected on diagnoses and outcome on three groups: men judged to need MPA who eventually went on to actually receive it; men recommended to receive MPA who, for a variety of reasons, did not receive the medication; and men deemed not to need MPA. Outcome measures included recidivism data, including reoffenses, parole violations, and reincarcerations, and whether these were sexual in nature. Data were also collected on employment and whether supervising officers believed the men in each group were doing well. Significant differences emerged among these three groups, with men actually receiving depo-Provera committing no new sexual offenses and also committing fewer overall offenses and violations compared to the other two groups. In addition, almost one third of men judged to need medication but who did not receive it committed a new offense and almost 60% of these were sexual in nature. While generalizations from these types of retrospective and partially subjective findings are inherently limited, the present study lends credence to the belief that, in selected offenders, anti-androgenic medication can be a valuable, if time-limited, addition to a cognitive and behavioral treatment program. Suggestions for more practical and far-reaching implementation of this adjunctive approach are offered.     

Therapeutic treatment of experimental colitis with regulatory dendritic cells generated with vasoactive intestinal peptide

BACKGROUND & AIMS: Crohn's disease is a chronic debilitating disease characterized by severe T helper cell (Th)1-driven inflammation of the colon partially caused by a loss of immune tolerance against mucosal antigens. The use of regulatory dendritic cells (DCs) with the capacity to induce regulatory T cells has been proposed recently for the treatment of Crohn's disease in a strategy to restore immune tolerance. Vasoactive intestinal peptide is an immunomodulatory neuropeptide that induces regulatory DCs. The aim of this study was to investigate the therapeutic effect of vasoactive intestinal peptide-induced regulatory DCs (DC(VIP)) in a murine model of colitis. METHODS: We examined the therapeutic action of DC(VIP) in the colitis induced by intracolonic administration of trinitrobenzene sulfonic acid, evaluating diverse clinical signs of the disease including weight loss, diarrhea, colitis, and histopathology. We also investigated the mechanisms involved in the potential therapeutic effect of DC(VIP), such as inflammatory cytokines and chemokines, Th1-type response, and the generation of regulatory T cells. RESULTS: DC(VIP) injection significantly ameliorated the clinical and histopathologic severity of colitis, abrogating body weight loss, diarrhea, and inflammation, and increasing survival. The therapeutic effect was associated with down-regulation of both inflammatory and Th1-driven autoimmune response, by regulating a wide spectrum of inflammatory mediators directly through activated macrophages, and by generating interleukin-10-secreting regulatory T cells with suppressive capacity on autoreactive T cells. CONCLUSIONS: The possibility to generate/expand ex vivo regulatory DC(VIP) opens new therapeutic perspectives for the treatment of Crohn's disease in human beings, and may minimize the dependence on nonspecific immunosuppressive drugs used currently for autoimmune disorders.     

Acetate produced in the mitochondrion is the essential precursor for lipid biosynthesis in procyclic trypanosomes

Acetyl-CoA produced in mitochondria from carbohydrate or amino acid catabolism needs to reach the cytosol to initiate de novo synthesis of fatty acids. All eukaryotes analyzed so far use a citrate/malate shuttle to transfer acetyl group equivalents from the mitochondrial matrix to the cytosol. Here we investigate how this acetyl group transfer occurs in the procyclic life cycle stage of Trypanosoma brucei, a protozoan parasite responsible of human sleeping sickness and economically important livestock diseases. Deletion of the potential citrate lyase gene, a critical cytosolic enzyme of the citrate/malate shuttle, has no effect on de novo biosynthesis of fatty acids from ¹⁴C-labeled glucose, indicating that another route is used for acetyl group transfer. Because acetate is produced from acetyl-CoA in the mitochondrion of this parasite, we considered genes encoding cytosolic enzymes producing acetyl-CoA from acetate. We identified an acetyl-CoA synthetase gene encoding a cytosolic enzyme (AceCS), which is essential for cell viability. Repression of AceCS by inducible RNAi results in a 20-fold reduction of ¹⁴C-incorporation from radiolabeled glucose or acetate into de novo synthesized fatty acids. Thus, we demonstrate that the essential cytosolic enzyme AceCS of T. brucei is responsible for activation of acetate into acetyl-CoA to feed de novo biosynthesis of lipids. To date, Trypanosoma is the only known eukaryotic organism that uses acetate instead of citrate to transfer acetyl groups over the mitochondrial membrane for cytosolic lipid synthesis.     

Méningiomes intracrâniens et utilisation prolongée d’acétate de cyprotérone à dose conventionnelle chez la femme : à propos de deux cas de régression tumorale après arrêt du traitement

The action of synthetic progestogens, prescribed at a conventional dose in women, for a meningioma, is still poorly understood, and could be related to progesterone receptors. We report two cases illustrating multiple meningiomas with stabilization or tumor reduction after withdrawal of cyproterone acetate originally prescribed for a long term period. We also review the influence of synthetic progestogens on meningiomas, particularly the impact of treatment withdrawal.     

Purification and characterization of a highly thermostable esterase from the actinobacterium Geodermatophilus obscurus strain G20

Intracellular thermostable esterase produced by the extremophilic Geodermatophilus obscurus G20 was purified to homogeneity by a heat treatment, followed by an anion‐exchange chromatography, and then characterized. The molecular weight of the purified enzyme determined by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) was shown to be approximatively 55 kDa. The enzyme showed an optimal activity between pH 8.0 and 9.0 and was stable in the pH range 7.0–10.0. Moreover, it is highly thermostable, with a residual activity greater than 90% after incubation at 80 °C for more than 10 h. The enzyme showed preference for esters of p ‐nitrophenol with short chain fatty acid. When the p ‐nitrophenyl acetate (C2) was used as substrate, the Michaelis–Menten constant (K_m) and maximum velocity for the reaction (V_max) of esterase were 400 μM and 2500 U/mg protein, respectively. The effect of phenylmethanesulphonyl fluoride (PMSF), a serine‐specific inhibitor, on the enzyme activity suggested that the thermostable esterase belong to the serine hydrolase group. Because of its high thermostability, activity at alkaline pH, tolerance to methanol and various metal ions and specificity for short chain fatty acids, this enzyme showed high potential for use in biocatalysis. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Ulipristal acetate: a new emergency contraceptive

Ulipristal acetate (UPA) is a newly developed emergency contraceptive currently available in the USA and Europe. It is approved as a 30 mg one-time dose taken within 120 h (5 days) of unprotected intercourse or failed contraception. This selective progesterone receptor modulator appears to be more effective than the levonorgestrel-containing emergency contraceptive, which must be taken within 72 h of unprotected intercourse. According to pharmacodynamic trials, UPA delays follicular maturation and ovulation. In addition, UPA may modulate the endometrium. Both Phase III clinical trials found that UPA does not lose efficacy within the 120-h dosing interval. Throughout all phases of clinical studies, UPA was shown to be well tolerated with only minimal adverse drug reactions, all of which are similar to competitor therapies.     

Ulipristal acetate and its role in emergency contraception: a comment

The use of selective progesterone modulators (SRMs) has been investigated extensively over the last few years. Ulipristal acetate (UPA) is an selective progesterone receptor modulator (SPRM) which has been in use since 2010 as an effective alternative emergency contraception (EC) regimen to Levonorgestrel (LNG). It acts by inhibiting ovulation and delaying implantation. Its effectiveness is active up to 120 h after sexual intercourse. UPA is safe and has a good tolerability profile. Health care practitioners should inform women of all reproductive ages that UPA is an effective alternative agent for those who are dissatisfied with other means of EC, and its activity of up to 120 h after sexual intercourse should also be highlighted.