Potential risks in drug prescriptions to elderly: a cross-sectional study in the public primary health care system of Ourinhos Micro-region, Brazil

This research aimed to assess the occurrence of potential risks in drug prescriptions to elderly at the Brazilian public primary health care. A cross-sectional, multicenter research was carried out at the pharmacies of public primary health care in five cities of the Ourinhos Micro-region, Sao Paulo, Brazil. Potential drug-drug interactions (DDIs) (according to three DDIs investigation software programs), drugs that act on cytochrome P450 system (CYP450) and potentially inappropriate medications (PIM) for elderly people (according to the Beers criteria (2003)) were selected as indicators of potential risks. A total of 2,627 prescriptions were collected and evaluated. Major DDIs were found in 2.6 % to 3.4 % of the prescriptions, depending on the software used. The prevalence of prescriptions containing drugs that acted on CYP450 was 50.9 %. PIM were found in 26.9 % prescriptions. These data indicate high prevalence of potential risks in drugs prescriptions to elderly at Ourinhos Micro-region public primary health care.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Selectivity of the antimetastatic and cytotoxic effects of 1-p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (+/-)-1,2-di(3,5-dioxopiperazin-1-yl)propane, and cyclophosphamide in mice bearing Lewis lung carcinoma.

The effects of two selective antimetastatic agents, 1-p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK), and (+/-)-1,2-di(3,5-dioxopiperazin-1-yl)propane, have been examined in comparison with those of a cytotoxic agent, cyclophosphamide, in mice bearing Lewis carcinoma. Cyclophosphamide at the two highest dosages causes a strictly related and pronounced inhibition (to less than 10\%) of the weight of the s.c. tumor, spontaneous metastases, and lung colonies formed after i.v. injection of tumor cells (artificial metastases); this behavior is consistent with a purely cytotoxic mechanism. At the three dosages used, (+/-)-1,2-di(3,5-dioxopiperazin-1-yl)propane reduces the weight of spontaneous metastases to less than 3\%. A dose-dependent reduction of artificial metastasis weight is also observed. At the highest dose, artificial metastasis weight is reduced to about 5\%, and s.c. tumor mass is significantly lowered to 40\%. These effects are consistent with the combined occurrence of cytotoxic and selective antimetastatic action, although the latter appears to be predominant. At the three dosages used, DM-COOK markedly depresses the weight and number of spontaneous metastases to about 10\%, leaving the formation of artificial metastases unaffected and causing no significant effect on primary tumor growth. The effects of these agents on the fractional incorporation of [3H]thymidine in tumor cells further indicate that only DM-COOK is devoid of cytotoxic effects for pulmonary and s.c. tumors. In hosts pretreated with DM-COOK, no reduction in the formation either of spontaneous or of artificial metastases is observed. These data indicate that DM-COOK acts directly on tumor cells and that it presumably inhibits their release from the primary tumor into the bloodstream

From Middle Jurassic heating to Neogene cooling: the thermochronological evolution of the southern Alps

The Dolomite region is located in the Southern Alps which were affected by a Mesozoic extensional tectonics and by consequent thermal perturbations. In this work, vitrinite reflectance and apatite fission-track analysis are used to estimate the thermal evolution. These methodologies have been applied to the Permo-Mesozoic succession which crops out along the TRANSALP seismic profile. The regional distribution of the organic matter maturity seems to be mainly controlled by different burial reached during the Norian-Liassic extensional phase, in connection with high heat flow values. The best solutions obtained from thermal modelling of both vitrinite and fission-track data suggest that peak of high heat flow occurred during Bajocian-Bathonian ages, when western Tethys was characterized by intrusions of gabbros and plagiogranites and extrusion of tholeiite basalts. This time coincides with the onset of the drifting phase and related thermal subsidence. Following thermal relaxation occurred during continous sedimentation and, therefore, maximum burial does not coincide with peak temperatures. Cooling history has been then carefully analyzed through apatite fission-track data on samples collected close to the Valsugana overthrust which document an important exhumation event at about 10 Ma. The related erosion has been analyzed through the combined use of arenite petrography and fission-track analysis on detrital samples of the Veneto foredeep succession, which represents the storage of detritus during Tertiary. These data confirm that after Serravalian the Southalpine domain and related covers were affected by subaerial erosion

Thermocronologial evolution of the Southern Alps alont the Transalp profile

none6noneM. ZATTIN; A. CUMAN; R. FANTONI; S. MARTIN; P. SCOTTI; C. STEFANIZattin, Massimiliano; Cuman, A.; Fantoni, R.; Martin, Silvana; Scotti, P.; Stefani, C

Invasive trophoblast promote stromal fibroblast decidualization via Profilin 1 and ALOX5

During the establishment of pregnancy, extravillous trophoblast (EVT) must invade into the uterine decidua to facilitate decidual artery remodelling to create the placental blood supply. The local decidual environment is thought to regulate trophoblast invasion, however these interactions are poorly defined in humans. Recent evidence in women suggests impaired decidualization is associated with miscarriage and preeclampsia. Primary human endometrial stromal cells (HESC) and first trimester extravillous trophoblast (EVTs) were used to assess the effect of EVT-secreted factors on HESC decidualization, adhesion, proliferation and migration. We determined the role of profilin (PFN)1, an EVT-secreted factor, on HESC function and identified a downstream target of PFN1. EVT-secreted factors induced HESC decidualization and enhanced decidualized HESC adhesion, proliferation and migration. Recombinant PFN1 enhanced methoxyprogesterone acetate-induced HESC decidualization and proliferation. PFN1 down-regulated the expression of lipoxygenase arachidonate 5-lipoxygenase (ALOX5) in HESC and THP-1 macrophages. ALOX5 localised to decidual cells and CD68+macrophages in 1st trimester decidua. This study demonstrated that EVT secretions, including PFN1, enhanced HESC decidualization and motility. This study has identified a new pathway that facilitates appropriate decidualization during the establishment of pregnancy

Galectin-7 acts as an adhesion molecule during implantation and increased expression is associated with miscarriage

The fulltext of this publication will be made publicly available after relevant embargo periods have lapsed and associated copyright clearances obtained.INTRODUCTION: Galectins are expressed at the fetal-maternal interface and have multiple roles including during blastocyst implantation. The expression of galectin-7 however has not been investigated in the uterus. We aimed to localise galectin-7 to the endometrium of women with normal fertility and with a history of miscarriage and prospectively determine whether serum levels are altered in women who subsequently miscarry. We also investigated the role of galectin-7 on trophoblast-endometrial epithelial cell adhesion. METHODS: Immunohistochemistry localised galectin-7 to endometrium throughout the menstrual cycle in women (normal fertility or with history of miscarriage) and in first trimester implantation sites. Galectin-7 serum levels were determined by ELISA. We used both endometrial epithelial-trophoblast cell lines and primary cells for cell-cell adhesion experiments. RESULTS: Galectin-7 immunolocalized to endometrial luminal and glandular epithelium in normally fertile women and was upregulated in epithelium and stroma of women with a history of miscarriage. Similarly, galectin-7 serum levels were elevated at 6 weeks gestation in women who subsequently miscarried compared to gestation matched controls. Exogenous galectin-7 reduced endometrial epithelial-trophoblast adhesion in cell-line and primary cell assays. However, when endometrial epithelial cells were isolated from women with endometrial disorders, galectin-7 increased epithelial-trophoblast adhesion. CONCLUSIONS: Galectin-7 is produced by endometrial epithelium and is abnormally elevated in the endometrium of women with a history of miscarriage. Serum levels may be useful as a predictive biomarker of miscarriage. Our data suggests that galectin-7 facilitates adhesion of the embryo to the endometrium and elevated galectin-7 may result in abnormal adhesion