Occupational exposure to pesticides deregulates systemic cortisol levels in women with breast cancer and correlates with poor prognosis features.

Pesticides have been pointed out as hormone disruptors and may significantly affect the prognosis of hormone-dependent diseases such as breast cancer (BC). Here, we investigated the impact of occupational pesticide exposure on systemic cortisol levels in female rural workers diagnosed with BC. Occupational exposure was assessed by interviews with a standardized questionnaire. Plasma samples (112 from pesticide-exposed women and 77 from unexposed women) were collected in the afternoon, outside the physiological cortisol peak, and analyzed by a chemiluminescent paramagnetic immunoassay for the quantitative determination of cortisol levels in serum and plasma. The results from both groups were categorized according to patients' clinicopathological and exposure data. BC pesticide-exposed women presented higher levels of cortisol than the unexposed. Higher cortisol levels were also detected in the exposed group with more aggressive disease (triple-negative BC), with tumors over 2 cm, with lymph node metastases, and with high risk of disease recurrence and death. These findings demonstrated that there is an association between pesticide exposure and BC that affected cortisol levels and correlated to poor disease prognosis.

Occupational exposure to pesticides deregulates systemic cortisol levels in women with breast cancer and correlates with poor prognosis features

Pesticides have been pointed out as hormone disruptors and may significantly affect the prognosis of hormone-dependent diseases such as breast cancer (BC). Here, we investigated the impact of occupational pesticide exposure on systemic cortisol levels in female rural workers diagnosed with BC. Occupational exposure was assessed by interviews with a standardized questionnaire. Plasma samples (112 from pesticide-exposed women and 77 from unexposed women) were collected in the afternoon, outside the physiological cortisol peak, and analyzed by a chemiluminescent paramagnetic immunoassay for the quantitative determination of cortisol levels in serum and plasma. The results from both groups were categorized according to patients' clinicopathological and exposure data. BC pesticide-exposed women presented higher levels of cortisol than the unexposed. Higher cortisol levels were also detected in the exposed group with more aggressive disease (triple-negative BC), with tumors over 2 cm, with lymph node metastases, and with high risk of disease recurrence and death. These findings demonstrated that there is an association between pesticide exposure and BC that affected cortisol levels and correlated to poor disease prognosis.

Footwear designed to enhance energy return improves running economy compared to a minimalist footwear: does it matter for running performance?

The present study compared the effects of a footwear designed to enhance energy return (thermoplastic polyurethane, TPU) vs minimalist shoes on running economy (RE) and endurance performance. In this counterbalanced and crossover design study, 11 recreational male runners performed two submaximal constant-speed running tests and two 3-km time-trials with the two shoe models. Oxygen uptake was measured during submaximal constant-speed running tests in order to determine the RE at 12 km/h and oxygen cost of running (CTO2) at individual average speed sustained during the 3-km running time-trials wearing either of the two shoes. Our results revealed that RE was improved (2.4%) with TPU shoes compared with minimalist shoes (P=0.01). However, there was no significant difference for CTO2 (P=0.61) and running performance (P=0.52) comparing the TPU (710±60 s) and the minimalist (718±63 s) shoe models. These novel findings demonstrate that shoes with enhanced mechanical energy return (i.e. TPU) produced a lower energy cost of running at low (i.e., 12 km/h) but not at high speeds (i.e., average speed sustained during the 3-km running time-trial, ∼15 km/h), ultimately resulting in similar running performance compared to the minimalist shoe.

Footwear designed to enhance energy return improves running economy compared to a minimalist footwear: does it matter for running performance?

The present study compared the effects of a footwear designed to enhance energy return (thermoplastic polyurethane, TPU) vs minimalist shoes on running economy (RE) and endurance performance. In this counterbalanced and crossover design study, 11 recreational male runners performed two submaximal constant-speed running tests and two 3-km time-trials with the two shoe models. Oxygen uptake was measured during submaximal constant-speed running tests in order to determine the RE at 12 km/h and oxygen cost of running (CTO2) at individual average speed sustained during the 3-km running time-trials wearing either of the two shoes. Our results revealed that RE was improved (2.4%) with TPU shoes compared with minimalist shoes (P=0.01). However, there was no significant difference for CTO2 (P=0.61) and running performance (P=0.52) comparing the TPU (710±60 s) and the minimalist (718±63 s) shoe models. These novel findings demonstrate that shoes with enhanced mechanical energy return (i.e. TPU) produced a lower energy cost of running at low (i.e., 12 km/h) but not at high speeds (i.e., average speed sustained during the 3-km running time-trial, ∼15 km/h), ultimately resulting in similar running performance compared to the minimalist shoe.

Biomass components and structure of massai grass fertilized with nitrogen and grazed by sheep / Componentes da biomassa e estrutura do capim-massai adubado com nitrogênio e pastejado por ovinos

To evaluate the biomass components of massai grass subjected to nitrogen (N) fertilization levels (control - 0; 400; 800 and 1200 kg ha-1 year-1 of N) and under rotational stocking with sheep, this study was undertaken using a completely randomized design with measurements repeated in time. A quadratic response was observed reaching maximum values as the levels of nitrogen fertilization increased for green forage biomass, green leaf biomass, green stem biomass (5,172.9; 4,146.3; 1,033.9 kg ha-1 cycle-1, respectively), forage total density (179.1 kg ha-1 cm-1), canopy height (36.8 cm) and live material/dead material ratio (4.0) at levels 896; 934; 797; 879.2; 751.4 and 1,161 kg ha-1 year-1 of N, respectively. For all variables, oscillation was observed between the grazing cycles studied. Nitrogen fertilization has a positive response on the biomass components and canopy structure of massai grass.(AU)

Objetivou-se avaliar os componentes da biomassa do capim-massai sob lotação rotativa com ovinos e adubado com doses de nitrogênio (controle - 0; 400; 800 e 1200 kg de N ha -1 ano -1 ), em delineamento inteiramente ao acaso, com medidas repetidas no tempo. Constatou-se resposta quadrática, alcançando valores máximos com o incremento das doses de nitrogênio para as produções de biomassa de forragem verde, de lâmina foliar verde, de colmo verde (5172,9; 4146,3; 1033,9 kg ha -1 ciclo -1 , respectivamente) e para a densidade total de forragem (179,1 kg ha -1 cm -1 ), altura do dossel (36,8 cm) e relação material vivo/material morto (4,0) nas doses 896; 934; 797; 879,2; 751,4 e 1161 kg ha -1 ano -1 de N, respectivamente. Para todas as variáveis, verificou-se oscilação entre os ciclos de pastejo estudados. A adubação nitrogenada exerce respostas positivas sobre os componentes da biomassa e a estrutura do dossel do capim-massai.(AU)

Evaluation of an environmentally sustainable UV-assisted water treatment system for the removal of Bacillus globigii spores in water.

Development of greener water treatment technologies is important for the production of safe drinking water and water security applications, such as decontamination. Chlorine assisted disinfection is common and economical, but can generate disinfection byproducts (DBPs) that may be of health concern. DBPs are formed due to the reaction of chlorine with naturally occurring organic and inorganic substances in water. Currently, various innovative technologies are being developed as alternative approaches for preventing DBPs during water treatment. In this study, we evaluated the effectiveness of a novel combination of high efficiency flow filtration and UV disinfection treatment system for the removal of Bacillus globigii (B. globigii) spores in water. The filtration system consists of a charged membrane filter (CMF) that not only helps to remove suspended particles but also reduces the impact of other impurities including bio organisms. In order to get most performance details, the CMF was evaluated at clean, half-life, and end of life (EOL) conditions along with 100% UV transmittance (UVT). In addition, the effectiveness of the UV system was evaluated as a stand alone system at 100% and 70% EOL intensity. The study was conducted at the US EPA's Test and Evaluation (T&E) Facility in Cincinnati, OH, using B. globigii, a surrogate for B. anthracis spores. This non-chemical environmentally-friendly CMF/UV combination system and the stand alone UV unit showed greater than 6.0 log removal of B. globigii during the tests.

A combination of nutrition and genetics is able to reduce age at puberty in Nelore heifers to below 18 months.

Nelore heifers usually begin their reproductive life at ⩾24 months of age mainly due to suboptimal nutritional conditions and genetics. This study aimed to determine the effect of expected progeny difference (EPD) for age at first calving and average daily gain (ADG) on puberty in Nelore (Bos taurus indicus) heifers. A total of 58 weaned heifers (initial BW=174±6 kg; age=9±1 months) were allocated into 28 feedlot pens. Heifers were born from four sires, of which two had low EPD for age at first calving (L; n=33) and two had high EPD for age at first calving (H; n=25). Then, heifers of each EPD were randomly assigned to high ADG (HG; 0.7 kg) or low ADG (LG; 0.3 kg), resulting in four treatments: heifers from L sires were submitted to either HG (LHG; n=17) or LG (LLG; n=16), and heifers from H sires were submitted to either HG (HHG; n=12), or LG (HLG; n=13). The HG heifers were fed a 75% grain diet, whereas the LG heifers received 93% of forage in their diet. Blood samples were collected at 9, 14, 18, 24 and 28 months of age for IGF1 and leptin determination. There was a treatment effect (P<0.01) on the proportion of heifers that attained puberty by 18 (62%, 0%, 0% and 0%), 24 (100%, 6%, 54% and 0%) or 36 (100%, 100%, 100% and 38%) months of age for LHG, LLG, HHG and HLG treatments, respectively. In addition, mean age at puberty was different across treatments (P<0.01). Heifers from the LHG achieved puberty at the earliest age when compared with cohorts from other treatments (18.1, 28.9, 23.9 and 34.5 months for LHG, LLG, HHG and HLG, respectively). Serum IGF1 concentrations were higher for L heifers compared with H cohorts at 9, 14, 18, 24 and 28 months of age (P<0.01; treatment×age interaction), whereas circulating leptin concentrations were higher (P<0.01; age effect) as heifers became older, regardless of the treatments. In conclusion, only Nelore heifers with favorable genetic merit for age at first calving were able to attain puberty by 18 months of age. In heifers with unfavorable genetic merit for age at first calving, supplementary feeding to achieve high ADG was unable to shift the age at puberty below 24 months.

Could formaldehyde induce mutagenic and cytotoxic effects in buccal epithelial cells during anatomy classes?

BACKGROUND: Due to increased formaldehyde exposure, carcinogenic to humans, several researches have been studying the potential toxicity and the safe levels for human beings. The aim of this study was to investigate mutagenicity and cytotoxicity in buccal epithelial exfoliated cells (BEC) of students subjected to formaldehyde (FA) during anatomy classes. MATERIAL AND METHODS: BEC were collected periodically from 17 volunteers of undergraduate programs, who had participated in practical anatomy classes, before and after FA exposure. Cells were stained according to Feulgen method and then micronucleus test was applied. A total of 1,500 cells were assessed per individual in this study for the micronucleus frequency and other parameters of cytotoxicity. RESULTS: There was statistically significant increase in number of micronucleated BEC after FA exposure (after 1 month p=.034 and after 3.5 months p=.017). However, FA exposure caused no significant increase in other nuclear alterations closely related to cytotoxicity (p≥.05). CONCLUSIONS: FA induced mutagenicity during anatomy classes. Cell death increased, but it was not statistically significant. Efforts have to be made to improve air quality and reduce exposures during anatomy classes.

HydroCalc Proteome: a tool to identify distinct characteristics of effector proteins.

Bacterial pathogenicity is associated with secretion of effector proteins into intra- and extracellular spaces. These proteins interfere with cellular processes such as inhibition of phagosome-lysosome fusion, induction of apoptosis and autophagy, activation and suppression of kinases, regulation of receptor activity, and modulation of transcription factors. Knowledge regarding the characteristics of these proteins would assist in pathogenicity studies, and help to identify possible and novel targets for antibacterial drugs. Amino acid hydropathy is a property that can affect behavior patterns in effector proteins. The HydroCalc Proteome tool analyzes total hydropathy, average hydropathy, C-terminal hydropathy, C-terminal load, and basic polar amino acids at the C-terminus. These five properties could contribute to the identification of proteins with an effector potential. HydroCalc Proteome is a web tool that provides a simple interface for the analysis of hydropathy properties in proteins. This tool permits the analysis of a single protein or even the complete proteome, which cannot be achieved by using other hydropathy tools. The tool displays the result of five properties related to effector proteins in a single table. The HydroCalc Proteome (www.gmb.bio.br/hydrocalc) is a powerful tool for protein analysis, and can contribute to the study of effector proteins.

Hidden prevalence of chronic kidney disease in hypertensive patients: the strategic role of primary health care.

OBJECTIVE: To identify the hidden prevalence of chronic kidney disease (CKD) in hypertensive patients. STUDY DESIGN: Cross-sectional study of individuals with systemic arterial hypertension (SAH) who were registered for primary health care (PHC). METHODS: In total, 293 individuals participated. Data were collected through interviews, as well as biochemical and anthropometric assessments. The CKD-EPI formula was used to identify the occurrence of CKD. Pearson's chi-squared test or Fisher's exact test were used to compare proportions. Prevalence ratios were estimated with a confidence interval of 95% for associations between the explanatory variables and CKD. RESULTS: Most of the individuals assessed were female (74%), elderly (69%), with a low income (90%), low education levels (84%) and overweight (66.9%). A CKD prevalence of 38.6% (95% CI: 33.0-44.2) was found and approximately 14% were at an advanced stage of the disease. Upon comparison of the variables in the different stages of CKD, statistically significant association could be suggested between CKD and age, education, alcohol intake, overweight individuals, cardiovascular risk, abnormal creatinine and abnormal microalbuminuria. When the prevalence ratio was assessed, association could be suggested between CKD and age, and CKD and creatinine. CONCLUSION: The high hidden prevalence of CKD confirms the need to train health professionals involved in the treatment of SAH through PHC, enabling the prevention and diagnosis of CKD in its early stages.

Helicobacter pylori infection is high in paediatric nonulcer dyspepsia but not associated with specific gastrointestinal symptoms.

AIM: The association between Helicobacter pylori infection and gastrointestinal symptoms is debatable in childhood. We examined the potential relationship between H. pylori infection and gastrointestinal symptoms in Brazilian children with nonulcer dyspepsia. METHODS: This prospective observational study analysed 240 Brazilian children and adolescents (68.7% girls) with chronic nonulcer dyspepsia, who underwent upper gastrointestinal endoscopy and biopsy. Their mean age was 9.8 years (range 4-17). Upper gastrointestinal symptoms, including abdominal pain, nausea, burning, early satiety, belching and weigh loss, were evaluated by a questionnaire and H. pylori infection was determined by histopathology of gastric biopsies. RESULTS: H. pylori infection was identified in 123/240 patients (52%). There was no significant association between the H. pylori infection and gastrointestinal symptoms and no relationship between the infection and abdominal pain or pain characteristics. However, nausea was significantly associated with the H. pylori infection, with an odds ratio of 1.76 and 95% confidence interval of 1.1-2.94 p < 0.03. Symptoms lasting longer than 12 months were significantly more frequent in children with pangastritis than in those with antral gastritis (p < 0.05). CONCLUSION: The prevalence of H. pylori infection was high in Brazilian children with nonulcer dyspepsia, but was not associated with specific signs and symptoms, except for nausea.

Purine nucleoside phosphorylase activity and expression are upregulated in sites affected by periodontal disease.

BACKGROUND AND OBJECTIVE: Purine nucleoside phosphorylase (PNP) is an enzyme that catalyzes the reversible phosphorolysis of purine nucleosides, playing a key role in the purine salvage pathway. Activated T cells seem to rely heavily on PNP to remain functionally active and are particularly sensitive to PNP deficiency. The role of PNP in periodontal tissues has not been characterized thus far. The aim of this study therefore was to assess the activity and expression of PNP in the gingival tissues of periodontitis patients. MATERIAL AND METHODS: Ten patients consecutively admitted for treatment had their periodontal clinical variables recorded and their gingival crevicular fluid collected. After periodontal treatment the patients were seen once a month for plaque and bleeding control, and had their periodontal variables recorded and gingival crevicular fluid collected at 90 and 180 d. Purine nucleoside phosphorylase-specific activity was assessed using a spectrophotometer through the addition of the PNP substrate analog 2-amino-6mercapto-7-methyl purine riboside to the gingival crevicular fluid. In parallel, PNP expression was assessed by immunohistochemistry and real-time PCR in gingival biopsies and cell culture. RESULTS: Purine nucleoside phosphorylase activity was higher in the gingival crevicular fluid of periodontally diseased sites, which was positively correlated with improvements of the clinical variables. Treatment of periodontal disease induced a striking decrease of PNP activity in periodontally diseased sites. Expression of PNP was more pronounced in mononuclear cells and endothelial cells of the gingiva, and the mRNA levels were 5.7-fold higher in inflamed tissues compared with control samples. CONCLUSION: Purine nucleoside phosphorylase activity and expression are upregulated in periodontally diseased sites and can be detected in the gingival crevicular fluid.

Intussusception in adults: a retrospective study.

OBJECTIVE: Intestinal intussusception in adult patients is rare. In contrast with paediatric patients, it is usually secondary to a definable lesion, often malignant. The purpose of this study was to determine the causes and the management of intussusception in adult patients. METHOD: A retrospective review was performed looking at patients over 18 years with intestinal intussusception who were admitted to a tertiary university hospital from 1997 to 2007. RESULT: There were 16 patients (out of whom 10 were female subjects) of mean age 49 years (range 19-76). All presented with abdominal pain and in seven (46.6%) patients, this was acute. The diagnosis of intussusception was correctly made preoperatively in eight (50%) patients. Six (37.5%) patients had the lead point for the intussusception at the ileocaecal valve, five (31.25%) in the small bowel and five (31.25%) had a colonic lead point. An anatomical cause was found in 14 (87.5%). In two (12.5%), the intussusception occurred in the postoperative period without any definable lesion. Half the patients had a malignant neoplasm. All patients underwent surgery. In 14 (87.5%) patients, this was by resection and in two (12.5%), a reduction with no resection was carried out. CONCLUSION: The features of intussusception may be nonspecific and the diagnosis is often made only during laparotomy. An identifiable organic lesion is present in most cases. En bloc resection is recommended for ileocaecal and colocolic intussusception.

Desempenho de ovinos em capim-tanzânia sob lotação rotativa com quatro proporções de suplementação concentrada / Performance of sheep raised on Tanzania grass under intermittent stocking with four proportions of concentrate supplementation

Avaliou-se o desempenho de ovinos em capim-tanzânia sob lotação rotativa com quatro proporções de suplementação concentrada 0 por cento, 0,6 por cento, 1,2 por cento e 1,8 por cento do peso vivo (PV), e oito repetições, em delineamento inteiramente ao acaso, com período de ocupação de três dias e descanso de 21 dias. Foram avaliados o ganho médio diário (GMD), o ganho de peso total (GPT), o número de dias para alcançar 12kg (D12), a taxa de lotação em ovinos/ha (TLO) e em UA/ha (TLUA), o rendimento de peso vivo (RPV) e a conversão alimentar do concentrado (CAC). Observou-se efeito quadrático da proporção de suplementação sobre o GMD que foi estimado em 65,87 e 113,15g/dia para os animais não suplementados e suplementados com 1,8 por cento do PV. O suplemento também teve efeito quadrático sobre o GPT. O D12 estimado para os ovinos não suplementados foi de 204 dias, reduzindo-se para 113 dias para os animais suplementados com 1,8 por cento do PV. Quanto à TLO e TLUA, observou-se efeito quadrático da proporção de suplementação. Observou-se efeito linear negativo da proporção de suplementação sobre RPV. A CAC foi melhor entre os animais suplementados com 0,6 por cento do PV. A utilização da suplementação até 1,2 por cento PV melhorou o desempenho dos ovinos em pastejo.

This study evaluated the performance of sheep raised on Tanzania grass under intermittent stocking with four supplementation proportions 0; 0.6; 1.2, and 1.8 percent of live weight (LW) and eight replicates, in a completely randomized design with tree grazing periods, and 21 rest periods. The average daily gain (GMD), the total weight gain (GPT), the days to reach 12kg (D12), the stocking rate (sheep/ha - TLO and animal unit/ha - TLUA), the live weight yield (RPV), and the concentrate: gain ratio (CAC) was evaluated. It was observed a square effect of supplementation proportions on GMD, estimated in 65.87 and 113.15g/day for male sheep that was not supplemented and received 1.8 percent LW supplement. It was observed a square effect of supplementation level on GPT. The D12 to 0 percent LW level was estimated in 204 days, decreasing to 113 days when the sheep received 1.8 percent LW supplement. It was observed square effects of supplementation proportions on TLO and TLUA. It was observed a negative linear effect of supplementation proportions on RPV. The CAC presented the best response for sheep that received 0.6 percent LW supplementation proportion. It can be concluded that sheep supplementation until 1.2 percent LW level provided improvement on performance of grazing sheep.

Gentamicin-induced preconditioning of proximal tubular LLC-PK1 cells stimulates nitric oxide production but not the synthesis of heat shock protein

Nephrotoxicity is the main side effect of antibiotics such as gentamicin. Preconditioning has been reported to protect against injuries as ischemia/reperfusion. The objective of the present study was to determine the effect of preconditioning with gentamicin on LLC-PK1 cells. Preconditioning was induced in LLC-PK1 cells by 24-h exposure to 2.0 mM gentamicin (G/IU). After 4 or 15 days of preconditioning, cells were again exposed to gentamicin (2.0 mM) and compared to untreated control or G/IU cells. Necrosis and apoptosis were assessed by acridine orange and HOESCHT 33346. Nitric oxide (NO) and endothelin-1 were assessed by the Griess method and available kit. Heat shock proteins were analyzed by Western blotting. After 15 days of preconditioning, LLC-PK1 cells exhibited a significant decrease in necrosis (23.5 ± 4.3 to 6.5 ± 0.3%) and apoptosis (23.5 ± 4.3 to 6.5 ± 2.1%) and an increase in cell proliferation compared to G/IU. NO (0.177 ± 0.05 to 0.368 ± 0.073 ìg/mg protein) and endothelin-1 (1.88 ± 0.47 to 2.75 ± 0.53 pg/mL) production significantly increased after 15 days of preconditioning compared toG/IU. No difference in inducible HSP 70, constitutive HSC 70 or HSP 90 synthesis in tubular cells was observed afterpreconditioning with gentamicin. The present data suggest that preconditioning with gentamicin has protective effects on proximal tubular cells, that involved NO synthesis but not reduction of endothelin-1 or production of HSP 70, HSC 70, or HSP 90. We conclude that preconditioning could be a useful tool to prevent the nephrotoxicity induced by gentamicin.

Gentamicin-induced preconditioning of proximal tubular LLC-PK1 cells stimulates nitric oxide production but not the synthesis of heat shock protein.

Nephrotoxicity is the main side effect of antibiotics such as gentamicin. Preconditioning has been reported to protect against injuries as ischemia/reperfusion. The objective of the present study was to determine the effect of preconditioning with gentamicin on LLC-PK1 cells. Preconditioning was induced in LLC-PK1 cells by 24-h exposure to 2.0 mM gentamicin (G/IU). After 4 or 15 days of preconditioning, cells were again exposed to gentamicin (2.0 mM) and compared to untreated control or G/IU cells. Necrosis and apoptosis were assessed by acridine orange and HOESCHT 33346. Nitric oxide (NO) and endothelin-1 were assessed by the Griess method and available kit. Heat shock proteins were analyzed by Western blotting. After 15 days of preconditioning, LLC-PK1 cells exhibited a significant decrease in necrosis (23.5 +/- 4.3 to 6.5 +/- 0.3%) and apoptosis (23.5 +/- 4.3 to 6.5 +/- 2.1%) and an increase in cell proliferation compared to G/IU. NO (0.177 +/- 0.05 to 0.368 +/- 0.073 microg/mg protein) and endothelin-1 (1.88 +/- 0.47 to 2.75 +/- 0.53 pg/mL) production significantly increased after 15 days of preconditioning compared to G/IU. No difference in inducible HSP 70, constitutive HSC 70 or HSP 90 synthesis in tubular cells was observed after preconditioning with gentamicin. The present data suggest that preconditioning with gentamicin has protective effects on proximal tubular cells, that involved NO synthesis but not reduction of endothelin-1 or production of HSP 70, HSC 70, or HSP 90. We conclude that preconditioning could be a useful tool to prevent the nephrotoxicity induced by gentamicin.

Canal transportation and centring ability of RaCe rotary instruments.

AIM: Evaluate, through computerized tomography, canal transportation and centring ability of RaCe rotary instruments after preparation of mesiobuccal root canals in maxillary molar teeth. METHODOLOGY: Twenty-seven teeth were submitted to three cone beam tomographic analyses, one preoperatively, and two after preparation with file size 35, .02 taper and size 50, .02 taper. Canal transportation and centring ability were measured with reference to the distance between the noninstrumented portion of the root canals and the mesial and distal periphery of the root, compared with images obtained after the preparation with size 35 and 50 instruments. RESULTS: Canal transportation after preparation with the size 35 file was 0.030 +/- 0.253 mm and after the size 50 file was 0.057 +/- 0.317 mm. The centring ratio values after preparation with the size 35 file was 0.42 +/- 0.32 and after the size 50 file was 0.54 +/- 0.29, with no significant statistical difference between the groups. CONCLUSIONS: RaCe instruments allowed the preparation of curved root canals with preparation diameters larger than those normally used with minimal canal transportation and adequate centring ability.

Purine nucleoside phosphorylase: a potential target for the development of drugs to treat T-cell- and apicomplexan parasite-mediated diseases.

Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of nucleosides and deoxynucleosides, generating ribose 1-phosphate and the purine base, which is an important step of purine catabolism pathway. The lack of such an activity in humans, owing to a genetic disorder, causes T-cell impairment, and thus drugs that inhibit human PNP activity have the potential of being utilized as modulators of the immunological system to treat leukemia, autoimmune diseases, and rejection in organ transplantation. Besides, the purine salvage pathway is the only possible way for apicomplexan parasites to obtain the building blocks for RNA and DNA synthesis, which makes PNP from these parasites an attractive target for drug development against diseases such as malaria. Hence, a number of research groups have made efforts to elucidate the mechanism of action of PNP based on structural and kinetic studies. It is conceivable that the mechanism may be different for PNPs from diverse sources, and influenced by the oligomeric state of the enzyme in solution. Furthermore, distinct transition state structures can make possible the rational design of specific inhibitors for human and apicomplexan enzymes. Here, we review the current status of these research efforts to elucidate the mechanism of PNP-catalyzed chemical reaction, focusing on the mammalian and Plamodium falciparum enzymes, targets for drug development against, respectively, T-Cell- and Apicomplexan parasites-mediated diseases.

Enrofloxacin assay validation and pharmacokinetics following a single oral dose in chickens.

The pharmacokinetics of enrofloxacin (ENRO), a fluoroquinolone antimicrobial agent, was studied in male broiler chickens (Cobb) after single oral administration of 10 mg of ENRO/kg b.w. A high-performance liquid chromatography-photodiode array detector (DAD) (HPLC-DAD) method was developed and validated and used for quantitation of ENRO and its major metabolite ciprofloxacin in plasma. The HPLC analyses were carried out using a cationic-octadecyl mixed column and 0.05 mol/L phosphate buffer (pH 2.5)/acetonitrile as mobile phase. The sample preparation of plasma consisted of the precipitation of proteins followed by solid phase extraction on cationic-octadecyl mixed cartridges. The method was validated considering linear range, linearity, selectivity, sensitivity, limit of detection (LOD), limit of quantitation (LOQ), intra- and inter-day precisions and accuracy. The LOD and LOQ for both fluoroquinolones were 60 and 200 ng/mL for plasma. The plasma concentration vs. time graph was characteristic of a two-compartment open model. The maximal plasma concentration of 1.5 +/- 0.2 mg/mL was achieved at 9 +/- 2 h. The elimination half-life and the mean residence time of ENRO were 1.5 +/- 0.2 and 15.64 h, respectively. The area under the concentration-time curve was calculated as 35 +/- 4 mgxh/mL.

Pseudomyxoma peritonei arising from colonic polyps.

AIMS: Pseudomyxoma peritonei may have as its primary site a mucinous gastrointestinal adenoma or carcinoma that gains access to the peritoneal cavity. This manuscript describes this disease arising from a benign or malignant colonic polyp. METHODS: From a database of over 1000 pseudomyxoma peritonei patients and colorectal carcinomatosis patients, three cases were identified in which the primary tumor site was a colonic polyp. The clinical history and course of these patients were studied. RESULTS: In a review of the clinical management of these patients, all three had an event whereby neoplastic cells from the surface of the colonic polyp could have gained access to the free peritoneal cavity. The patients developed the characteristic pseudomyxoma peritonei syndrome. All three patients were treated with cytoreductive surgery plus perioperative hyperthermic intraperitoneal chemotherapy. CONCLUSIONS: Colonic polyps can serve as a source of dysplastic cells whereby pseudomyxoma peritonei can result. Caution to prevent seeding to the free peritoneal cavity during surgery for colonic polyps should be observed. If pseudomyxoma peritonei develops, cytoreductive surgery and perioperative intraperitoneal chemotherapy should be considered for treatment.