Possible inhibition of hydroxy methyl glutaryl CoA reductase activity by nicotinic acid and ergosterol: as targeting for hypocholesterolemic action.

Objective: Coronary artery diseases including atherosclerosis is considered as commonest problem worldwide. Ergosterols are the main components of vegetable oils and nuts. The objective of this study was to evaluate the potential hypoplipidemic and hypocholesterolemic effects of ergosterol in combination with niacin in rats fed high fat diet (HFD). Methods: Eighty male albino rats were included in this study divided into two main groups: Group I: Normal rats fed standard diet treated with either niacin (8.5 mg /kg b.w) or ergosterol (100 mg/kg b.w) or both. Group II; rats fed HFD treated with either niacin (8.5 mg /kg b.w) or ergosterol (100 mg/kg b.w) or both The feeding and treatment lasted for 8 weeks. Results: A significant elevation in the levels of total cholesterol, triacylglycerol, VLDL-c, LDL-c and atherogenic factor (p<0.001) in rats fed on HFD compared with normal control while HDL-c was significantly reduced in HFD rats compared with control group. Supplementation of diet with niacin or ergosterol or combined exerts improvement in the studied parameters by lowering triacylglycerol, total cholesterol, LDL-c and atherogenic factor and elevate HDL-c near to the value of control. Niacin combined with ergosterol were effective in the reduction of hydroxy methyl glutaryl-CoA reducatase (HMGCoA) compared with control (p<0.001). The combined effect was more potent than individual alone. Conclusion: Utilization of niacin and ergosterol may prevent the hypercholesterolemia and incidence of coronary heart diseases. These functional foods act as nutriceutical as dyslipidemics.

Estudo da adesão de pinos endodônticos modificados superficialmente por plasma de oxigênio

The work presents the effect of plasma treatment when applied in fibers or carbon/glass posts in the adhesion fiber/resin and posts/cement. This has for objective the modification of the surface of the fibers, as well as the wettability of the posts, seeking the improvement of the adhesion and of the connection fiber/resin in the processing of polymeric composites reinforced with the same ones. 120 posts (Reforpost) were used and 30 meters of fibers of carbon and of glass (Fibrex), of the company Angelus. The samples were divided in three groups of 40 specimens: GROUP I - 20 posts of glass fiber and 20 of carbon without treatment to it shapes, GROUP II -20 posts of glass fiber and 20 of carbon treated to it shapes in the surface and GROUP III - 20 posts of glass fiber and 20 of carbon make with fibers in natura after plasma treatment. The plasma treatment was accomplished with oxygen and with temperature in the camera fixed at 200°C, for one hour of exhibition. The posts and the fibers were characterized before and after the treatment. The wettability was measure by pendent drop method, and interface fiber/resin and posts/cement were observed by optical and electronic microscopy. It was observed that both wettability and texture were increased with plasma treatment

Filogenia molecular do gênero Sicalis (passeriformes, aves) : enfoque na filogeografia do canário-da-terra (Sicalis flaveola)

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Biológicas, Departamento de Ciências Fisiológicas, Programa de Pós Graduação em Biologia Animal, 2015.

Reabsorción radicular externa apical en incisivos y caninos superiores e inferiores sometidos a tratamiento de Ortodoncia en etapa inicial

La Reabsorción radicular externa apical es un proceso inflamatorio común asociado con el tratamiento de ortodoncia. El objetivo de este estudio fue comparar la magnitud de la RREA de los incisivos y caninos superiores e inferiores en pacientes sometidos a la fase inicial del tratamiento de ortodoncia con tres diferentes tipos de brackets. La muestra consistió en 23 casos de pacientes con edades comprendidas entre 12 y 27 años, fueron divididos aleatoriamente en 3 grupos. Grupo I (n=9; 5 mujeres y 4 varones), utilizando brackets pasivos de autoligado Damon Q Grupo II (n= 8; 4 mujeres y 4 varones) utilizando brackets convencionales prescripción Roth y MBT. Grupo III (n=6; 4 mujeres y 2 varones) utilizando brackets Biofuncional QR. Se analizaron 264 dientes (caninos e incisivos superiores e inferiores) mediante el uso de tomografía computarizada de haz cónico (NewTom VGi Cone Beam 3D Imaging), con el escáner NNT Viewer (versión 4.6 NewTom). Los resultados obtenidos indican que la media de reabsorción se mostró distinta para los diferentes protocolos de tratamiento, así como diferente de acuerdo a la pieza analizada, sin embargo, la prueba de ANOVA no encontró diferencias estadísticamente significativas al comparar la media de reabsorción de cada pieza por tipo de brackets empleados o tratamiento realizado (p >0,05). Se concluye que la RREA se ha producido en todos los dientes evaluados, durante los 6 primeros meses de tratamiento y el diseño del bracket (autoligado pasivo, convencional o QR) no influye en el grado de reabsorción radicular.

Plasma D-lactate Levels in Necrotizing Enterocolitis in Premature Infants

Background: D-Lactate is normally present in the blood of humans at nanomolar concentrations due to methylglyoxal metabolism; millimolar D-lactate concentrations can arise due to excess gastrointestinal microbial production. Objectives: To examine the levels of plasma D-lactate in the necrotizing enterocolitis in premature infants. Patients and Methods: 128 premature infants were divided into control (group I, n = 69), feeding intolerance (group II, n = 42) and NEC (group III, n = 27) groups. Plasma D-lactate levels were measured at the onset of feeding intolerance or NEC and at weeks 2-3 in control infants (group I) by ELISA. Data were analyzed using descriptive statistics, non-parametric tests and Student’s t-test. Results: In groups I, II, III, median birth weights were 1845.7 ± 267.5 g, 1913.1 ± 306.5 g, and 1898.4 ± 285.3 g, median gestational ages were 34.3 ± 1.7 weeks, 33.9 ± 2.2 weeks and 35.1 ± 2.6 weeks, ages of sampling were 12.3 ± 2.9 days, 14.6 ± 3.7 days and 15.1 ± 1.8 days, respectively. The differences of median birth weights, median gestational ages and ages of sampling were not statistically significant (P > 0.05). The plasma D-lactate levels in groups I, II, III were 3.6 ± 1.9 μg/mL, 12.7 ± 8.3 μg/mL, and 35.4 ± 29.1 μg/mL, respectively, group III had higher plasma D-lactate level than groups I, II, and the difference among these groups was significant (x2 = 21.6, P < 0.01). Conclusions: Plasma D-lactate significantly increased early in NEC. Plasma D-lactate levels were associated with extensive disease in NEC infants. Therefore, it could be used as a diagnosis indicator in the early stage of NEC.

Antibiotic Therapy for Very Low BirthWeigh Newborns in NICU

Background: Prolonged empiric antibiotics therapy in neonates results in several adverse consequences including widespread antibiotic resistance, late onset sepsis (LOS), necrotizing enterocolitis (NEC), prolonged hospital course (HC) and increase in mortality rates. Objectives: To assess the risk factors and the outcome of prolonged empiric antibiotic therapy in very low birth weight (VLBW) newborns. Materials and Methods: Prospective study in VLBW neonates admitted to NICU and survived > 2 W, from July 2011 - June 2012. All relevant perinatal and postnatal data including duration of antibiotics therapy (Group I < 2W vs Group II > 2W) and outcome up to the time of discharge or death were documented and compared. Results: Out of 145 newborns included in the study, 62 were in group I, and 83 in Group II. Average duration of antibiotic therapy was 14 days (range 3 - 62 days); duration in Group I and Group II was 102.3 vs 25.510.5 days. Hospital stay was 22.311.5 vs 44.3 14.7 days, respectively. Multiple regression analysis revealed following risk factors as significant for prolonged empiric antibiotic therapy: VLBW especially < 1000 g, (P < 0.001), maternal Illness (P = 0.003), chorioamnionitis (P = 0.048), multiple pregnancy (P = 0.03), non-invasive ventilation (P < 0.001) and mechanical ventilation (P < 0.001). Seventy (48.3%) infants developed LOS; 5 with NEC > stage II, 12 (8.3%) newborns died. Infant mortality alone and with LOS/NEC was higher in group II as compared to group I (P < 0.002 and < 0.001 respectively). Conclusions: Prolonged empiric antibiotic therapy caused increasing rates of LOS, NEC, HC and infant mortality

Early and late effects of Ibuprofen on mouse sperm parameters, chromatin condensation, and DNA integrity in mice

Background: There are few studies indicating the detrimental effects of ibuprofen on sperm fertility potential and DNA integrity. Objective: To determine the effects of Ibuprofen on sperm parameters, chromatin condensation and DNA integrity of mice. Materials and Methods: In this experimental study, 36 adult male mice with average weight 37 gr were divided into three groups, including control (group I, n=12), normal dosage of ibuprofen (group II, n=12) and high dosage (group III, n=12). Ibuprofen with different doses was dissolved in daily water of animals. After 35, 70 and 105 days, the cauda epididymis of mice were cut and incubated in Ham’s F10 media. Sperm samples were analyzed for parameters (motility, morphology and count), DNA integrity (SCD test) and chromatin condensation (chromomycin A3 and Aniline blue staining). Results: After 35 days, in addition to above mentioned sperm parameters, all of the treated mice showed statistically significant increase in spermatozoa with immature chromatin (P<0.05). However, after 70 days, the rate of sperm DNA fragmentation assessed by SCD was increased in group II (66.5±0.7) and the percentage of immature spermatozoa (AB+ and CMA3+) was higher in group III (77.5±0.7 and 49.5±6.3 respectively) than other groups. After 105 days, the AB+ spermatozoa were increased in both normal dose and high dose groups. Conclusion: Ibuprofen may cause a significant reduction in sperm parameters and sperm chromatin/DNA integrity in mice. It should be noted that these deleterious effects are dose-dependent and can be seen in early and late stage of drug treatments.

Development of metabotropic glutamate receptors from trigeminal nuclei to barrel cortex in postnatal mouse

Expression patterns of group I (mGluR1α and mGluR5)and group II (mGluR2/3) metabotropic glutamate receptor subtypes were examined immunocytochemically in the trigeminal system of mice during the first 3 weeks of postnatal development, when somatotopic whisker representations are sequentially established from brainstem through thalamus to cerebral cortex. Immunostaining for all three epitopes formed whisker-related patterns in the trigeminal nuclei from postnatal day (P) 0, in the ventral posterior thalamic nucleus from P2, and in the posteromedial barrel subfield of somatosensory cortex (SI) from P4. The appearance of whisker-related patterns was preceded by increased levels of immunostaining of the neuropil, which subsequently declined from the trigeminal nuclei upward. In SI, mGluR1α-positive neurons were observed in all cortical layers from P2. mGluR5 was localized in neurons, glial cells, and neuropil from P2. mGluR2/3 immunostaining was distributed only in the neuropil at all ages. The three receptor subtypes showed moderate to high expression in deep layer V throughout development. Transient expression peaked in the hollows of layer IV barrels from P4 to P9, and then fell off as expression increased in supragranular layers from P14 to P21. The deep aspect of the cortical subplate (layer VIb) showed dense mGluR5 and less dense mGluR1α immunostaining throughout development. Up-regulation of expression of group I and II mGluRs is correlated with the growth and refinement of connectivity and the establishment of somatotopic patterns in the three main relay stations of the trigeminal system. This finding suggests roles for mGluRs in the early processing of sensory information and in developmental plasticity.

Molecular simulations and modeling of pharmaceutically relevant RNA-processing enzymes

The two-metal-ion architecture is a structural feature found in a variety of RNA processing metalloenzymes or ribozymes (RNA-based enzymes), which control the biogenesis and the metabolism of vital RNAs, including non-coding RNAs (ncRNAs). Notably, such ncRNAs are emerging as key players for the regulation of cellular homeostasis, and their altered expression has been often linked to the development of severe human pathologies, from cancer to mental disorders. Accordingly, understanding the biological processing of ncRNAs is foundational for the development of novel therapeutic strategies and tools. Here, we use state-of the-art molecular simulations, complemented with X-ray crystallography and biochemical experiments, to characterize the RNA processing cycle as catalyzed by two two-metal-ion enzymes: the group II intron ribozymes and the RNase H1. We show that multiple and diverse cations are strategically recruited at and timely released from the enzymes’ active site during catalysis. Such a controlled cations’ trafficking leads to the recursive formation and disruption of an extended two-metal ion architecture that is functional for RNA-hydrolysis – from substrate recruitment to product release. Importantly, we found that these cations’ binding sites are conserved among other RNA-processing machineries, including the human spliceosome and CRISPR-Cas systems, suggesting that an evolutionarily-converged catalytic strategy is adopted by these enzymes to process RNA molecules. Thus, our findings corroborate and sensibly extend the current knowledge of two-metal-ion enzymes, and support the design of novel drugs targeting RNA-processing metalloenzymes or ribozymes as well as the rational engineering of novel programmable gene-therapy tools.

Anti-Group A Streptococcal Vaccine Epitope STRUCTURE, STABILITY, AND ITS ABILITY TO INTERACT WITH HLA CLASS II MOLECULES

Streptococcus pyogenes infections remain a health problem in several countries due to poststreptococcal sequelae. We developed a vaccine epitope (StreptInCor) composed of 55 amino acids residues of the C-terminal portion of the M protein that encompasses both T and B cell protective epitopes. The nuclear magnetic resonance (NMR) structure of the StreptInCor peptide showed that the structure was composed of two microdomains linked by an 18-residue alpha-helix. A chemical stability study of the StreptInCor folding/unfolding process using far-UV circular dichroism showed that the structure was chemically stable with respect to pH and the concentration of urea. The T cell epitope is located in the first microdomain and encompasses 11 out of the 18 alpha-helix residues, whereas the B cell epitope is in the second microdomain and showed no alpha-helical structure. The prediction of StreptInCor epitope binding to different HLA class II molecules was evaluated based on an analysis of the 55 residues and the theoretical possibilities for the processed peptides to fit into the P1, P4, P6, and P9 pockets in the groove of several HLA class II molecules. We observed 7 potential sites along the amino acid sequence of StreptInCor that were capable of recognizing HLA class II molecules (DRB1*, DRB3*, DRB4*, and DRB5*). StreptInCoroverlapping peptides induced cellular and humoral immune responses of individuals bearing different HLA class II molecules and could be considered as a universal vaccine epitope.

Early toxicity from preoperative radiotherapy with continuous infusion 5-fluorouracil for resectable adenocarcinoma of the rectum: A phase II trial for the Trans-Tasman Radiation Oncology Group

Purpose: To assess the toxicity and the efficacy of preoperative radiotherapy with continuous infusion 5-fluorouracil (5-FU) for locally advanced adenocarcinoma of the rectum. Methods and Materials: Eligible patients had newly diagnosed localized adenocarcinoma of the rectum within 12 cm of the anal verge, Stage T3-4, and were suitable for curative resection. Eighty-two patients were treated with radiotherapy-50.4 Gy in 28 fractions in 5.6 weeks, given concurrently with continuous infusion 5-FU, using either 96-h/week infusion at 300 mg/m(2)/day or 7-days/week infusion at 225 mg/m(2)/day. Results: The median age was 59 years (range, 27-87), and 67% of patients were male. Pretreatment stages of the rectal cancer were T3, 89% and resectable T4, 11%, with endorectal ultrasound confirmation in 67% of patients. Grade 3 acute toxicity occurred in 5 of 82 patients (6%; 95% confidence interval [CI], 2-14%). Types of surgical resection were anterior resection, 61%; abdominoperineal resection, 35%; and other procedures, 4%. There was no operative mortality. Anastomotic leakage after low anterior resection occurred in 3 of 50 patients (6%; 95% CI, 1-17%). The pathologic complete response rate was 16% (95% CI, 9-26%). Pathologic Stages T2 or less occurred in 51%. Conclusion: Preoperative radiotherapy with continuous infusion 5-FU for locally advanced rectal cancer is a safe regimen, with a significant downstaging effect. It does not seem to lead to a significant increase in serious surgical complications. (C) 2001 Elsevier Science Inc.

Antibody levels to the class I and II epitopes of the M protein and myosin are related to group A streptococcal exposure in endemic populations

Rheumatic fever (RF)/rheumatic heart disease (RHD) and post-streptococcal glomerulonephritis are thought to be autoimmune diseases, and follow group A streptococcal (GAS) infection. Different GAS M types have been associated with rheumatogenicity or nephritogenicity and categorized into either of two distinct classes (I or II) based on amino acid sequences present within the repeat region ('C' repeats) of the M protein. Sera from ARF patients have previously been shown to contain elevated levels of antibodies to the class I-specific epitope and myosin with the class I-specific antibodies also being cross-reactive to myosin, suggesting a disease association. This study shows that immunoreactivity of the class I-specific peptide and myosin does not differ between controls and acute RF (ARF)/RHD in populations that are highly endemic for GAS, raising the possibility that the association is related to GAS exposure, not the presence of ARF/RHD. Peptide inhibition studies suggest that the class I epitope may be conformational and residue 10 of the peptide is critical for antibody binding. We demonstrate that correlation of antibody levels between the class I and II epitope is due to class II-specific antibodies recognizing a common epitope with class I which is contained within the sequence RDL-ASRE. Our results suggest that antibody prevalence to class I and II epitopes and myosin is associated with GAS exposure, and that antibodies to these epitopes are not an indicator of disease nor a pathogenic factor in endemic populations.

Revision of the genus Macrostomus Wiedemann (Diptera: Empididae: Empidinae): II. The pictipennis species-group

All species of Macrostomus Wiedemann allied with Macrostomus pictipennis (Bezzi), are treated in the pictipennis species-group. Three currently recognized species and four new species are included, namely M. cervicicauda Smith, M. cysticercus Smith, M. manauara, sp. nov. from Brazil (Amazonas and Pará states), M. pacaraima, sp. nov. from Brazil (Roraima, Amazonas and Pará states), M. pictipennis (Bezzi), M. smithi, sp. nov. from Guyana and Brazil (Roraima State) and M. utinga, sp. nov. from Brazil (Pará State). All primary types were examined and a key to species is presented.

Clinical benefit of fulvestrant in postmenopausal women with advanced breast cancer and primary or acquired resistance to aromatase inhibitors: final results of phase II Swiss Group for Clinical Cancer Research Trial (SAKK 21/00).

BACKGROUND: The aim of this study was to evaluate the efficacy and tolerability of fulvestrant, an estrogen receptor antagonist, in postmenopausal women with hormone-responsive tumors progressing after aromatase inhibitor (AI) treatment. PATIENTS AND METHODS: This is a phase II, open, multicenter, noncomparative study. Two patient groups were prospectively considered: group A (n=70) with AI-responsive disease and group B (n=20) with AI-resistant disease. Fulvestrant 250 mg was administered as intramuscular injection every 28 (+/-3) days. RESULTS: All patients were pretreated with AI and 84% also with tamoxifen or toremifene; 67% had bone metastases and 45% liver metastases. Fulvestrant administration was well tolerated and yielded a clinical benefit (CB; defined as objective response or stable disease [SD] for >or=24 weeks) in 28% (90% confidence interval [CI] 19% to 39%) of patients in group A and 37% (90% CI 19% to 58%) of patients in group B. Median time to progression (TTP) was 3.6 (95% CI 3.0 to 4.8) months in group A and 3.4 (95% CI 2.5 to 6.7) months in group B. CONCLUSIONS: Overall, 30% of patients who had progressed following prior AI treatment gained CB with fulvestrant, thereby delaying indication to start chemotherapy. Prior response to an AI did not appear to be predictive for benefit with fulvestrant.

MMP-9 as predictive factor for response and progression free survival in breast cancer patients treated with bevacizumab and pegylated liposomal doxorubicin. A multicenter, single-arm phase II trial (SAKK24/06). On behalf of the Swiss Group for Clinical Cancer Research (SAKK).

The benefit of bevacizumab (Bv) has been shown in different tumors including colorectal cancer, renal cancer, pulmonary non-small cell cancer and also breast cancer. However to date, there is no established test evaluating the angiogenic status of a patient and monitoring the effects of anti-angiogenic treatments. Tumor angiogenesis is the result of a balance between multiple pro- and anti¬angiogenic molecules. There is very little published clinical data exploring the impact of the anti-angiogenic therapy on the different angiogenesis-related molecules and the potential role of these molecules as prognostic or predictive factors.