Low-dose flutamide (125 mg/day) as maintenance therapy in the treatment of hirsutism

OBJECTIVE: To evaluate the safety and efficacy of a low dose of flutamide (125 mg/day) in maintaining the clinical results already obtained using a higher dose (250 mg/day), in women suffering from hirsutism. METHOD: Forty-three women suffering from hirsutism of varying origin received 250 mg/day of flutamide as an initial treatment for 12 months and, subsequently, 125 mg/day of flutamide for an additional 12 months as a maintenance treatment. Hirsutism was evaluated by the Ferriman-Gallwey score, and hair diameter and hair growth rate were determined by a special image analysis processor. Biochemical, clinical and hormonal parameters were evaluated in basal conditions and every 2-6 months. RESULTS: The significant decrease in the hirsutism score, hair diameter and hair growth rate during the initial treatment period was confirmed at the end of the maintenance treatment period. Androgen levels decreased up to the end of the initial treatment period and partially decreased during the maintenance treatment. During the initial treatment period, 4 subjects showed an increase of aspartate aminotransferase and alanine aminotransferase and dropped out. During the maintenance treatment period, no side effects or complications were observed. CONCLUSION: Satisfactory management of hirsutism with flutamide seems to be represented by an initial treatment period using 250 mg/day to achieve satisfactory results, followed by a long maintenance treatment period using 125 mg/day.     

Susceptibility profile of vaginal yeast isolates from Brazil

Vaginal specimens for culture were obtained from two hundred and five immunocompetent, non-hospitalized patients selected among all women attending the Gynecology and Obstetric Ambulatory Clinic of the University of Espírito Santo, Brazil, during a 2-year period (From 1998 to 1999). Patients were checked for signs and symptoms of vulvovaginitis and previous use of topical and systemic antifungal drugs. Yeast isolates were identified by classical methods and the antifungal susceptibility profile was determined according to NCCLS microbroth assay. The prevalence of vaginal yeast isolates from asymptomatic women was 25% (30/121) and 60% (50/84) among patients with symptoms of vulvovaginitis. Candida albicans was the most frequently isolated species in both groups (46% and 90%, respectively), followed by C. glabrata (13% and 6%, respectively). All isolates were susceptible to amphotericin B. Only ten isolates had dose dependent susceptibility (DDS) or resistance to azoles; and seven of these were non-albicans species. Based on our results we suggest that species identification and antifungal susceptibility testing need not be routinely performed in immunocompetent women, and may be reasonable only for the minority of patients with complicated vulvovaginal candidiasis that fail to respond to therapy.     

Multicenter evaluation of the phosphorylcholine-coated biodivYsio stent in short de novo coronary lesions: The SOPHOS study

AIMS: The BiodivYsio trade mark stent (Biocompatibles Ltd, Farnham, UK) is coated with a phosphorylcholine (PC)-containing copolymer to confer biocompatibility. The SOPHOS (Study Of PHosphorylcholine coating On Stents) study was designed to assess the safety and efficacy of this novel coronary stent and by indirect comparison to indicate equivalence with other formal stent studies. METHODS AND RESULTS: Patients with angina and a single short (#x2A7F;12 mm) de novo lesion in a native coronary artery of >/=2.75 mm diameter were included. A total of 425 patients were allocated in 24 centers. Clinical data were collected at one-, six- and nine-month follow-up. Angiography was performed before and after the stent implantation. In addition, in the first 200 patients (SOPHOS A) angiography was routinely performed at six months. The following 225 patients (SOPHOS B) were merely followed up clinically. The primary end-point of the study, the six-month MACE-rate (MACE = Major Adverse Cardiac Events) was 13.4% (two cardiac death; five Q-wave/nine non-Q-wave myocardial infarctions (MI); nine CABG and 32 target lesion revascularization (TLR), which is similar to the calculated 15% MACE-rate in comparable reference studies. Secondary end-points included among others restenosis at six months in the SOPHOS A population. The target vessel diameter was 2.98 +/- 0.48 mm. Minimal lumen diameter pre/post procedure and at follow-up was 1.00 +/- 0.32, 2.69 +/- 0.37, 1.91 +/- 0.71 mm, respectively. The binary restenosis rate (>/=50% diameter stenosis at follow-up) was 17.7%. CONCLUSION: The coronary BiodivYsio stent is safe and effective as a primary device for the treatment of native coronary artery lesions in patients with stable or unstable angina pectoris. Clinical and angiographic results are in the statistical range of equivalence with comparable studies with other current stents.     

Effect of drying methods on retention of moist sucralfate gel properties

The aim of this work was to find a drying procedure for moist sucralfate gel capable of producing dried sucralfate gel that retains the original gel properties of bioadhesion, rheology, and micromeritics. Spray-drying and microwave-drying procedures were employed. Mannitol was used as a gel-protective substance during the drying processes. The spray drying of moist sucralfate gel gave rise to a powder whose water suspensions showed significantly reduced viscosity. The bioadhesion of spray-dried sucralfate gel was strongly reduced by drying. When mannitol was used as a gel protector, the spray-dried sucralfate in part maintained the original bioadhesion of moist sucralfate gel. The preparation of a dried sucralfate gel retaining the bioadhesion characteristics, avoiding the use of mannitol, was made possible using the microwavedrying procedure. The microwave-dried product possesses a granular morphology suitable for direct compression because it is a free flowing and strongly coherent granular powder.     

Special Issue Dedicated to Dr. Héctor S. Barra

Dedication

Special Issue Dedicated to Dr. Héctor S. Barra     

Fish Communities in Central Amazonian White- and Blackwater Floodplains

In Amazonian floodplains, the flood cycle of the river is becoming the dominant seasonal factor, and fish communities are found to fluctuate greatly over the year. During inundation, fish migrate into floodplain forests to feed on fruits and seeds, in an area more than 300000km² in size. To document patterns of species diversity, distribution, abundance and temporal dynamics and in order to describe the ecological importance of the inundated forest, floodplain fish were captured using variously sized gill nets in white and black water areas inside and outside the floodplain forests during low, rising, high and falling water level in 1990 and 1991. Dominance varies to some extent in white water between floodplain forest (0.06) and open water (0.11) while it is unchanged in black water (0.04). Black water fish communities were more diverse. Most abundant among white water fish were Liposarcus pardalis, Pygocentrus nattereri, and Pellona flavipinnis, for example, or Plagioscion squamsissimus, Serrasalmus rhombeus, and Serrasalmus manueli in black water. Among the most abundant white water fish, Colossoma macropomum, Mylossoma duriventre and Osteoglossum bicirrhosum occurred almost exclusively in inundated forests. Of the black water species there were a large number of species which were captured only in inundated forest, such as Geophagus cf. altifrons, Hoplias malabaricus, Osteoglossum bicirrhosum and Uaru amphiacanthoides. Catches varied with sample site, water level and direction of water level change. The average CPUE in white and black water was 190 and 41g fishm^–2 and day, respectively, with maximum yields at low water and minimum yields at high water. Comparing rising and falling water levels, a significantly higher quantity of fishes was captured at falling water level. In black water, fish catches from the floodplain forest exceeded the open water catch by 183 to 550%, depending on season. Differences in respect of white water are smaller (106–281%). Fish communities in the area under investigation seem to be stochastically assembled, with significant differences between white and black water only. Many fishes move into the floodplain forest not only to feed but probably also for other reasons – to seek shelter, for example.     

Multiple AGAMOUS homologs from cucumber and petunia differ in their ability to induce reproductive organ fate.

The C function in Arabidopsis, which specifies stamen and carpel identity, is represented by a single gene called AGAMOUS (AG). From both petunia and cucumber, two MADS box genes have been isolated. Both share a high degree of amino acid sequence identity with the Arabidopsis AG protein. Their roles in specifying stamen and carpel identity have been studied by ectopic expression in petunia, resulting in plants with different floral phenotypes. Cucumber MADS box gene 1 (CUM1) induced severe homeotic transformations of sepals into carpelloid structures and petals into stamens, which is similar to ectopic AG expression in Arabidopsis plants. Overexpression of the other cucumber AG homolog, CUM10, resulted in plants with partial transformations of the petals into antheroid structures, indicating that CUM10 is also able to promote floral organ identity. From the two petunia AG homologs pMADS3 and Floral Binding Protein gene 6 (FBP6), only pMADS3 was able to induce homeotic transformations of sepals and petals. Ectopic expression of both pMADS3 and FBP6, as occurrs in the petunia homeotic mutant blind, phenocopies the pMADS3 single overexpresser plants, indicating that there is no additive effect of concerted expression. This study demonstrates that in petunia and cucumber, multiple AG homologs exist, although they differ in their ability to induce reproductive organ fate.     

Involvement of distinct G-proteins, Gpa2 and Ras, in glucose- and intracellular acidification-induced cAMP signalling in the yeast Saccharomyces cerevisiae.

Adenylate cyclase activity in Saccharomyces cerevisiae is dependent on Ras proteins. Both addition of glucose to glucose-deprived (derepressed) cells and intracellular acidification trigger an increase in the cAMP level in vivo. We show that intracellular acidification, but not glucose, causes an increase in the GTP/GDP ratio on the Ras proteins independent of Cdc25 and Sdc25. Deletion of the GTPase-activating proteins Ira1 and Ira2, or expression of the RAS2(val19) allele, causes an enhanced GTP/GDP basal ratio and abolishes the intracellular acidification-induced increase. In the ira1Delta ira2Delta strain, intracellular acidification still triggers a cAMP increase. Glucose also did not cause an increase in the GTP/GDP ratio in a strain with reduced feedback inhibition of cAMP synthesis. Further investigation indicated that feedback inhibition by cAPK on cAMP synthesis acts independently of changes in the GTP/GDP ratio on Ras. Stimulation by glucose was dependent on the Galpha-protein Gpa2, whose deletion confers the typical phenotype associated with a reduced cAMP level: higher heat resistance, a higher level of trehalose and glycogen and elevated expression of STRE-controlled genes. However, the typical fluctuation in these characteristics during diauxic growth on glucose was still present. Overexpression of Ras2(val19) inhibited both the acidification- and glucose-induced cAMP increase even in a protein kinase A-attenuated strain. Our results suggest that intracellular acidification stimulates cAMP synthesis in vivo at least through activation of the Ras proteins, while glucose acts through the Gpa2 protein. Interaction of Ras2(val19) with adenylate cyclase apparently prevents its activation by both agonists.