Cytostatic in vitro Effects of DTCM-Glutarimide on Bladder Carcinoma Cells

Bladder cancer is a common malignancy worldwide. Despite the increased use of cisplatin-based combination therapy, the outcomes for patients with advanced disease remain poor. Recently, altered activation of the PI3K/Akt/mTOR pathway has been associated with reduced patient survival and advanced stage of bladder cancer, making its upstream or downstream components attractive targets for therapeutic intervention. In the present study, we showed that treatment with DTCM-glutaramide, a piperidine that targets PDK1, results in reduced proliferation, diminished cell migration and G1 arrest in 5637 and T24 bladder carcinoma cells. Conversely, no apoptosis, necrosis or autophagy were detected after treatment, suggesting that reduced cell numbers in vitro are a result of diminished proliferation rather than cell death. Furthermore previous exposure to 10 mu g/ml DTCM-glutarimide sensitized both cell lines to ionizing radiation. Although more studies are needed to corroborate our findings, our results indicate that PDK1 may be useful as a therapeutic target to prevent progression and abnormal tissue dissemination of urothelial carcinomas.

LIFE QUALITY of PEOPLE INFECTED BY HIV WITH OR WITHOUT ANTIRETROVIRAL TREATMENT

The "HIV/Aids-Quality of Life" (HAT-Qol) is a specific multifunctional instrument used to measure the life quality of HIV infected persons. It is divided into nine domains: general activity, sexual activity, secrecy about HIV seropositivity, concern about health, financial concern, awareness about HIV, satisfaction with life, issues about medications and belief in the doctor. The current study analyzed the life quality of HIV infected individuals-who attended the DST/Aids Program in Maringa city, Parana state-regarding the use or not of antiretroviral therapy (TARV) and their demographic, epidemiological and clinical characteristics. Data were collected by retrospective analysis from 1,200 medical charts of patients registered in the program. The HAT-Qol instrument was applied before routine medical consultation. One hundred and sixty-nine patients, who had HIV infection confirmed, were divided into two groups, G1 with 118 individuals receiving antiretroviral therapy and G2 with 51 individuals who were not under this therapy.Result analysis, regarding social and demographic characteristics, revealed no difference among responses related to gender, educational degree and sexual option. Age influenced satisfaction with sexual activity and marital status. Regarding HIV awareness, the lowest response index or worst quality of life came from, respectively, men between 50 and 69 years old and patients who did not have regular partners compared with the ones who did. Additionally, it was observed that the time of diagnosis influenced general activities, HIV awareness, concern about health and financial issues, satisfaction with life and topics about medications. The variables were compared in both groups. There was no influence on the use or not of antiretroviral therapy regarding age, sexual activity, HIV diagnosis time and the domains that evaluated general activities, financial concern, awareness of HIV and satisfaction with life. In relation to time of diagnosis, there was an influence only in persons who had been diagnosed two or three years before, in which a lower quality of life was observed among individuals who were not under antiretroviral therapy. It was not possible to compare variables about medication use, HIV plasmatic viral rate ant time of diagnosis, because G2 individuals were not receiving the antiretroviral therapy. Furthermore, no comparison was made regarding marital status and HIV awareness, because there were no married individuals in G2. Thus, the analysis of the results showed that the use of antiretroviral treatment did not influence the life quality of HIV patients studied by the HAT-Qol scale.

Población folicular y concentraciones plasmáticas de progesterona (P4) en ovejas sometidas a diferentes protocolos de sincronización

Los efectos de la prostaglandina (PGF2α) vs CIDR y eCG (gonadotrofina coriónica equina) en la dinámica de la población folicular y su relación con las concentraciones plasmáticas de P4 fueron investigadas en ovejas cíclicas. Fueron utilizadas 14 hembras ovinas de la raza Bergamascia; el Grupo 1 (Gl) se sometió a dos aplicaciones de PGF2α, y, el Grupo 2 (G2) tratado con CIDR durante 14 días siendo que, en el momento de su retirada, se administraron 500 UI de eCG. La dinámica folicular ovárica fue monitoreada por medio de ecógrafo. Se monitorearon todos los folículos ≥ mm y se gráfico su posición diariamente, observándose el desarrollo individual folicular. Desde el día anterior a la aplicación de la segunda dosis de PGF2α, (Gl) y desde la administración de eCG (G2) hasta el décimo día del ciclo estral se colectaron muestras de sangre para el análisis de P4. Hubo diferencia significativa (P<0,001) en las concentraciones plasmáticas de P4 entre los tratamientos. La sincronización del estro y ovulación utilizando CIDR + 500 UI de eCG, incrementó la cantidad de folículos reclutados, además de aumentar el diámetro máximo y la tasa de crecimiento de los folículos grandes en la primera onda folicular. En consideración a los resultados se puede concluir que la sincronización del estro y de la ovulación en hembras ovinas, utilizando el CIDR y 500 UI de eCG, incrementa la cantidad de folículos reclutados, además de aumentar el diámetro máximo y la tasa de crecimiento de los folículos grandes. La asociación CIDR+500 UI de eCG provoca aumentos significativos en las concentraciones plasmáticas de progesterona (P4) al inicio de la fase luteal en hembras ovinas.

Different substances and dry-needling injections in patients with myofascial pain and headaches

Trigger point injections with different solutions have been studied mainly with regard to the management of myofascial pain (MFP) patient management. However, few studies have analyzed their effect in a chronic headache population with associated MFP. The purpose of this study was to assess if trigger point injections using lidocaine associated with corticoid would be better than lidocaine alone, as in comparison with dry-needling in for the management of local pain and associated headache management. Forty-five (45) myofascial pain patients with headaches that could be reproduced by activating at least one trigger point, were randomly assigned into one of the three groups: G1, dry-needling, G2, 0.25% lidocaine, at 0.25% and G3, 0.25% lidocaine at 0.25% associated with corticoid, and were assessed during a 12 week period. Levels of pain intensity, frequency and duration, local post-injection sensitivity, obtainment time and duration of relief, and the use of rescue medication were evaluated. Statistically, all three groups showed favorable results for the evaluated requisites (p <= 0.05), but only for post-injection sensitivity did the association of lidocaine with corticoid present the best results and ingestion of rescue medication.

TEGDMA-induced oxidative DNA damage and activation of ATM and MAP kinases

The development of strategies for the protection of oral tissues against the adverse effects of resin monomers is primarily based on the elucidation of underlying molecular mechanisms. The generation of reactive oxygen species beyond the capacity of a balanced redox regulation in cells is probably a cause of cell damage. This study was designed to investigate oxidative DNA damage, the activation of ATM, a reporter of DNA damage, and redox-sensitive signal transduction through mitogen-activated protein kinases (MAPKs) by the monomer triethylene glycol dimethacrylate (TEGDMA). TEGDMA concentrations as high as 3-5 mm decreased THP-1 cell viability after a 24 h and 48 h exposure, and levels of 8-oxoguanine (8-oxoG) increased about 3- to 5-fold. The cells were partially protected from toxicity in the presence of N-acetylcysteine (NAC). TEGDMA also induced a delay in the cell cycle. The number of THP-1 cells increased about 2-fold in G1 phase and 5-fold in G2 phase in cultures treated with 3-5 mm TEGDMA. ATM was activated in THP-1 cells by TEGDMA. Likewise, the amounts of phospho-p38 were increased about 3-fold by 3 mm TEGDMA compared to untreated controls after a 24 h and 48 h exposure period, and phospho-ERK1/2 was induced in a very similar way. The activation of both MAPKs was inhibited by NAC. Our findings suggest that the activation of various signal transduction pathways is related to oxidative stress caused by a resin monomer. Signaling through ATM indicates oxidative DNA damage and the activation of MAPK pathways indicates oxidative stress-induced regulation of cell survival and apoptosis. (C) 2008 Elsevier Ltd. All rights reserved.

Evaluation of Sperm DNA Peroxidation in Fertile and Subfertile Dogs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Histology and morphometry of the testes of adult domestic cats (Felis catus)

Testicles of 30 mongrel cats were analyzed histologically and morphometrically, divided into three groups: G1 (1-2 years old), G2 (over 2 and up to 4 years old) and G3 (over 4 and up to 6 years old). After orchiectomy and histopathology, the morphometric parameters studied were: thickness of the tunica albuginea (72 mu m) and seminiferous epithelium (77.19 mu m), perimeter (53.81; 90.57 mu m), (54.80; 101.07 mu m); area (174.23; 494.55 mu m(2)), (176.68; 629.70 mu m(2)); maximum diameter (14.94; 28.02 mu m), (14.76; 31.66 mu m); minimum diameter (13.25; 21.92 mu m), (13.30; 24.52 mu m); and shape factor (index for regularity of the format) (1.36; 1.36), (1.39; 1.35) of the nucleus and cytoplasm of spermatogonia and Leydig cells, respectively. The results can be used for comparative studies and contribute knowledge concerning the height of the seminiferous epithelium, thickness of the tunica albuginea and size of spermatogonia and Leydig cells.

Use of specular microscopy to determine corneal endothelial cell morphology and morphometry in enucleated cat eyes

The purpose of this study was to investigate the effect of age on endothelial morphology and morphometry in cats. The corneal endothelium was studied using a contact specular microscope. A total of 18 cats (Felis catus Linnaeus, 1758) were evaluated in this study. The subjects were divided into three groups of six cats each in function of age: G1 (1 to 3 months old), G2 (5 to 12 months old), and G3 (24 to 40 months old). The examination presented data as endothelial cell density (ECD), average cell area, corneal thickness, polymegathism, and pleomorphism. Results revealed ECD decrease in corneas of normal cats with age, as well as a corresponding increase in endothelial cell area and pleomorphism. The present work suggests that the endothelial parameters evaluated change with advancing age.

Expression and Function of Fibroblast Growth Factor 18 in the Ovarian Follicle in Cattle

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effects of Passiflora edulis on the Metabolic Profile of Diabetic Wistar Rat Offspring

Dry extract of the genus Passiflora has been shown to help control glycemia and lipid levels. The objective of this study was to evaluate the effects of passion fruit (P. edulis) on the biochemical profile of offspring from diabetic rats. Diabetes was induced by streptozotocin. The diabetes group consisted of 10 rats with glucose levels greater than 200 mg/dL; the nondiabetic (control) group consisted of 10 rats with glucose levels less than 120 mg/dL. After the diagnosis of diabetes, the mating phase was started. By day 21 of pregnancy, the offspring were born; the dams were kept in individual cages with their offspring until the weaning period. The offspring were then divided into 4 groups (n = 15 each): G1 were offspring from control dams, G2 were offspring from treated nondiabetic dams, G3 were offspring from diabetic dams, and G4 were offspring from treated diabetic dams. For 30 consecutive days, G1 and G3 offspring were treated with vehicle (oral gavage) and G2 and G4 offspring were treated with passion fruit juice (oral gavage). After 30-day treatment, the animals were anesthetized and killed, and blood was drawn immediately for analysis of the biochemical profile (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and glucose). The G2 and G4 rats showed significantly reduced total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels and an increased high-density lipoprotein cholesterol level. The use of passion fruit juice improved lipid profiles, suggesting that this plant may have beneficial effects in the prevention and treatment of dyslipidemias and hyperglycemia.

Efeitos de baixas doses de cloprostenol via intramuscular ou submucosavulvar na indução do estro e taxas de prenhez em vacas Nelore

The present study aims to compare the effects of lower doses of cloprostenol intramuscular (IM) or into vulvar submucosa (IVS) on estrus induction and pregnancy rate in Nelore cows. A total of 100 cycling Nelore cows with body condition score (BCS 3.5) 1 to 5 scale (Radostitis; Blood, 1986) and 170 +/- 11 days postpartum. Females were randomly divided in 5 groups (N=20) G1 to G5 and treated with cloprostenol (Ciosin (R)) on day 0 (D0) and on day 11 (D11) if not detected in estrus. Cows were injected with 500 mu g IM (G1), 250 mu g IM (G2), 125 mu g IM (G3), 250 mu g IVS (G4) and 125 mu g IVS (G5). Estrus was observed twice a day and the females artificially inseminated 12 hours after heat detection. There was no statistical difference (P>0.80) between groups in the estrus induction (first injection to estrus interval): 16/20-96.00 hours (G1), 13/20-90.42 hours (G2), 10/20-84.45 hours (G3), 15/20-87.86 hours (G4), 12/20-81.25 hours (G5) and second injection (P>0.10): 4/20-67.50 hours (G1), 7/20-85.50 hours (G2), 10/20-57.00 hours (G3), 5/20-70.60 hours (G4), 8/20-60.00 hours (G5). There was no statistical difference (0.65(ns)) between groups in the pregnancy rates: 40% (G1), 45% (G2), 50% (G3), 40% (G4), 40% (G5). The results demonstrate that the treatments with lower doses of cloprostenol intramuscular or into vulvar submucosa may be used to induce heat with similar pregnancy rates in cycling Nelore cows with good body condition.

Ultrastructural analysis of bovine oocytes from ovarian follicles with different diameters

In vitro embryo production is an important technique for facilitating the reproduction of animals with high genetic merit. The greatest challenge for the reproducibility of this technique is the quality of the oocyte that is submitted for in vitro maturation. The aim of this work was to evaluate the ultrastructural characteristics of oocytes from follicles of different diameters using transmission electron microscopy. The animals were divided into 2 groups and were given a single i.m. injection of 250 IU FSH (Pluset, Serono, Italy). To synchronize the follicular growth, all follicles > 2 mm were aspirated during the estrous cycle, which was considered day zero (D0). Group 1 (G1; n = 4) received FSH on day 1 (D1), and the 2- to 5-mm follicles were aspirated on day 2 (D2). The animals in group 2 (G2; n = 5) received FSH on day 2 (D2), and their 10- to 15-mm follicles were aspirated on day 5 (D5). After aspiration, the oocytes from both groups were fixed and prepared for ultrastructural analysis. The oocytes analyzed from both groups had similar ultrastructural characteristics. The presence and distribution of organelles in the cytoplasm of the oocytes did not differ between groups, suggesting that, in relation to the ultrastructural characteristics, oocytes from 2 to 5 mm and 10 to 15 mm follicles are similar.

Pressure evaluation of the antireflux ability of the rat ureterovesical junction

The bladder pressure necessary to cause vesicoureteral reflux (VUR) was measured in 16 female rats. Under general anesthesia, the ureters were exposed via an abdominal incission and a pressure catheter was placed near the uterovesical junction. Values of bladder distension and bladder pressure increase to cause VUR were obtained by injecting isotonic saline in one ureter until VUR in the opposite ureter was detected as a sudden pressure increase. After 5 min the same procedure was done on the contralateral side. This procedure was repeated eight times in each rat with a 15-min intermission. The bladder pressure at which VUR occurred was measured through a uretral catheter. Two groups were studied: G1, control, and G2, administration of intravenous metoclopramide (0.007 mg/100 g body weight) four times.

Expression of beta-human chorionic gonadotropin (beta-hCG) in non-trophoblastic elements of transitional cell carcinoma of the bladder: possible relationship with the prognosis.

Transitional cell carcinoma (TCC) of the bladder is a neoplasm with variability in its clinical behavior. Although there are several studies correlating stage and ABO isoantigen expression with invasiveness, there is no single predictor factor to assess the potential invasiveness, especially in the low grade, non-invasive TCC. In the present study we evaluated the correlation of histological grade plus stage and the expression of beta human chorionic gonadotropin (beta-hCG), in 100 cases of TCC, with the clinical behavior. These features were correlated with tumor progression in patients with at least two years of follow up. We observed more aggressiveness in G4 group (high grade and invasive) (93% had tumor progression) when compared to G1 group (low grade and superficial) (11% had tumor progression). However in 25.5% of the TCC cases (groups G2: low grade and invasive and G3: high grade and superficial) the clinical behavior was intermediate, showing some limitation in using grading and staging only, as a predictive factor. There was an expression of beta-hCG in 21.4% of the cases in up to 25% of the tumor cells without any trophoblastic morphology. These beta-hCG producing TCC had a strong correlation with aggressiveness: 39.1% and 12.8% of the TCC expressed beta-hCG with and without tumor progression, respectively.

EFEITOS DA INFUSAO CONTINUA DO PROPOFOL SOBRE A FUNCAO RENAL DO CAO. ESTUDO COMPARATIVO COM O PENTOBARBITAL SODICO

Little research has been done with propofol in relation to renal function. The aim of this study was to evaluate the effects of the continuous infusion of propofol on renal function in dogs. Sixteen dogs, previously anesthetized with pentobarbital sodium (30 mg.kg-1) for surgical preparation, catheterism and monitoring, were studied. The dogs were mechanically ventilated with air and received alcuronium (0.2 mg.kg-1 in bolus and 0.06 mg.kg-1 - maintenance). The following parameters were studied: heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), aortic blood flow (A(o)BF - by electromagnetic flowmeter installed in the ascending aortic), aortic vascular resistance index (A(o)VRI), renal plasma flow (ERPF - by para-aminohipurate clearance), glomerular filtration rate (GFR - by creatinine clearance), effective renal blood flow (ERBF = ERPF/1 - hematocrit), urinary volume (UV), renal vascular resistance (RVR = MAP.80/ERBF.10-3), urinary sodium excretion (UE(Na)), fractionated sodium excretion (FE(Na)), osmolar clearance (C(osm)) and free water clearance (C(H2O)). These parameters were studied at 15 (M1), 30 (M2), 45 (M3) and 60 (M4) min after beginning pentobarbital sodium infusion (5 mg.kg-1.h-1). The dogs were allocated into two groups of eight animals each: G1 (control-pentobarbital sodium) and G2 (propofol). In G1, pentobarbital was given at the four times studied. G2 dogs received the same treatment as G1 dogs at M1 and M2; infusion of pentobarbital was substituted by propofol (3 mg.kg-1 bolus, followed by 12 mg.kg-1.h-1 continuous infusion) at M3 and M4. Profile Analysis was used to analyze the results statistically. In G1 (pentobarbital), there was a significant increase in RVR (M1 < M4) and a decrease in ERPF and ERBF (M1 > M4). In G2 (propofol) there was only a significant increase in A(o)BF (M1 < M2 = M3). In comparison among groups, these was a significant alteration of FE(Na) at M3 (pentobarbital > propofol). It was observed that the continuous infusion of propofol in dogs, at the given doses, did not alter the basic variables of renal function and hemodynamics studied. We concluded that propofol can be one of the drugs of choice to provide base anesthesia in studies of renal function in dogs.