A model of hemorrhagic cystitis induced with acrolein in mice

Acrolein is a urinary metabolite of cyclophosphamide and ifosfamide, which has been reported to be the causative agent of hemorrhagic cystitis induced by these compounds. A direct cytotoxic effect of acrolein, however, has not yet been demonstrated. In the present study, the effects of intravesical injection of acrolein and mesna, the classical acrolein chemical inhibitor, were evaluated. Male Swiss mice weighing 25 to 35 g (N = 6 per group) received saline or acrolein (25, 75, 225 µg) intravesically 3, 6, 12, and 24 h before sacrifice for evaluation of bladder wet weight, macroscopic and histopathological changes by Gray's criteria, and 3 and 24 h for assessment of increase in vascular permeability. In other animals, mesna was administered intravesically (2 mg) or systemically (80 mg/kg) 1 h before acrolein. Intravesical administration of acrolein induced a dose- and time-dependent increase in vascular permeability and bladder wet weight (within 3 h: 2.2- and 21-fold increases in bladder wet weight and Evans blue dye exuded, respectively, at doses of 75 µg/bladder), as confirmed by Gray's criteria. Pretreatment with mesna (2-mercaptoethanesulfonic acid), which interacts with acrolein resulting in an inactive compound, inhibited all changes induced by acrolein. Our results are the first demonstration that intravesical administration of acrolein induces hemorrhagic cystitis. This model of acrolein-induced hemorrhagic cystitis in mice may be an important tool for the evaluation of the mechanism by which acrolein induces bladder lesion, as well as for investigation of new uroprotective drugs.

Proteomic inventory of myocardial proteins from patients with chronic Chagas' cardiomyopathy

Chronic Chagas' disease cardiomyopathy (CCC) is an often fatal outcome of Trypanosoma cruzi infection, with a poorer prognosis than other cardiomyopathies. CCC is refractory to heart failure treatments, and is the major indication of heart transplantation in Latin America. A diffuse myocarditis, plus intense myocardial hypertrophy, damage and fibrosis, in the presence of very few T. cruzi forms, are the histopathological hallmarks of CCC. To gain a better understanding of the pathophysiology of CCC, we analyzed the protein profile in the affected CCC myocardium. Homogenates from left ventricular myocardial samples of end-stage CCC hearts explanted during heart transplantation were subjected to two-dimensional electrophoresis with Coomassie blue staining; protein identification was performed by MALDI-ToF mass spectrometry and peptide mass fingerprinting. The identification of selected proteins was confirmed by immunoblotting. We demonstrated that 246 proteins matched in gels from two CCC patients. They corresponded to 112 distinct proteins. Along with structural/contractile and metabolism proteins, we also identified proteins involved in apoptosis (caspase 8, caspase 2), immune system (T cell receptor ß chain, granzyme A, HLA class I) and stress processes (heat shock proteins, superoxide dismutases, and other oxidative stress proteins). Proteins involved in cell signaling and transcriptional factors were also identified. The identification of caspases and oxidative stress proteins suggests the occurrence of active apoptosis and significant oxidative stress in CCC myocardium. These results generated an inventory of myocardial proteins in CCC that should contribute to the generation of hypothesis-driven experiments designed on the basis of the classes of proteins identified here.

Antibody response to pneumococcal capsular polysaccharide vaccine in Down syndrome patients

The majority of children with Down syndrome (DS) tend to have frequent bacterial infections including recurrent respiratory infections. Our objective was to evaluate the production of antibodies to pneumococcal polysaccharide antigens after active immunization in DS subjects. IgG antibodies to pneumococcal serotypes (1, 3, 6B, 9V, and 14) were measured before and 6 weeks after immunization with a 23-valent pneumococcal vaccine (Pneumo23®, Pasteur-Merrieux) in 6- to 13-year-old DS children (N = 17) and in aged-matched normal controls (N = 30). An adequate response was defined as a 4-fold increase over baseline or a post-immunization level of specific pneumococcal serotype antibody > or = 1.3 µg/mL. After immunization, all DS children had an increase in post-immunization levels against all serotypes analyzed. A 4-fold or more increase was observed in all DS children concerning serotypes 1 and 14, in 90% of subjects for serotypes 3 and 9V, and in 65% for serotype 6B. Regarding this increase, 8 of the 17 DS children had an adequate response to all serotypes analyzed, 8/17 patients to 4 serotypes and 1/17 to 3 serotypes. However, when we compared post-immunization levels between DS children and controls, we observed lower levels in the former group (P < 0.05) for all serotypes except serotype 3. We conclude that pneumococcal polysaccharide immunization could be beneficial for these DS children.

Comparison of serum hormone levels of captive and free-living maned wolves Chrysocyon brachyurus

Serum hormone levels were compared between captive and free-living maned wolves and seasonal variations of sex hormones were studied. Blood samples were collected from 16 male and 26 female adult animals from Brazilian zoos, and from 30 male and 24 female free-living adults to determine serum progesterone and testosterone by radioimmunoassay. Serum testosterone concentrations varied (P < 0.05) across seasons for 16 captive males, being higher in autumn (2184.7 ± 355.1 pg/mL) than in summer (1080.7 ± 205.4 pg/mL), winter (1270.1 ± 276.6 pg/mL) and spring (963.9 ± 248.1 pg/mL), although they did not differ between summer, winter and spring. Testosterone concentration of 30 free-living males differed (P < 0.05) between autumn (824.1 ± 512.2 pg/mL), winter (14.4 ± 8.0 pg/mL) and spring (151.9 ± 90.5 pg/mL). Comparison between captive and free-living animals showed no difference in autumn (P > 0.05). Sixteen captive males showed higher testosterone concentration during winter and spring compared with 30 free-living animals (P < 0.05). Progesterone concentration varied among seasons in 26 captive females (P < 0.05), being higher in autumn (15.3 ± 3.1 ng/mL) than in summer (6.6 ± 1.5 ng/mL), winter (5.3 ± 3.1 ng/mL) and spring (4.3 ± 0.7 ng/mL). Progesterone concentration of 24 free-living females varied between autumn (17.1 ± 6.0 ng/mL) and winter (1.7 ± 0.3 ng/mL) (P < 0.05), but we could not obtain data for spring or summer. No difference in progesterone levels was observed between captive and free-living females in autumn and winter.

Diabetic retinopathy is associated with early autonomic dysfunction assessed by exercise-related heart rate changes

Diabetic retinopathy has been associated with cardiac autonomic dysfunction in both type 1 and type 2 diabetes mellitus (DM) patients. Heart rate (HR) changes during exercise testing indicate early alterations in autonomous tonus. The aim of the present study was to investigate the association of diabetic retinopathy with exercise-related HR changes. A cross-sectional study was performed on 72 type 2 and 40 type 1 DM patients. Autonomic dysfunction was assessed by exercise-related HR changes (Bruce protocol). The maximum HR increase, defined as the difference between the peak exercise rate and the resting rate at baseline, and HR recovery, defined as the reduction in HR from the peak exercise to the HR at 1, 2, and 4 min after the cessation of the exercise, were determined. In type 2 DM patients, lower maximum HR increase (OR = 1.62, 95%CI = 1.03-2.54; P = 0.036), lower HR recovery at 2 (OR = 2.04, 95%CI = 1.16-3.57; P = 0.012) and 4 min (OR = 2.67, 95%CI = 1.37-5.20; P = 0.004) were associated with diabetic retinopathy, adjusted for confounding factors. In type 1 DM, the absence of an increase in HR at intervals of 10 bpm each during exercise added 100% to the odds for diabetic retinopathy (OR = 2.01, 95%CI = 1.1-3.69; P = 0.02) when adjusted for DM duration, A1c test and diastolic blood pressure. In conclusion, early autonomic dysfunction was associated with diabetic retinopathy. The recognition of HR changes during exercise can be used to identify a high-risk group for diabetic retinopathy.

The prevalence of chronic diabetic complications and metabolic syndrome is not associated with maternal type 2 diabetes

The maternal history of type 2 diabetes mellitus (DM) has been reported more frequently in patients with type 2 DM than paternal history. The aim of the present study was to determine if there was an association between maternal history of DM and the presence of chronic complications or metabolic syndrome (MetS) in patients with type 2 DM. A cross-sectional study was conducted with 1455 patients with type 2 DM. All outpatients with type 2 diabetes attending the endocrine clinics who fulfilled the eligibility criteria were included. Familial history of DM was determined with a questionnaire. Diabetic complications were assessed using standard procedures. The definition of MetS used was that of the World Health Organization and the National Cholesterol Education Program's Adult Treatment Panel III report criteria. Maternal history of DM was present in 469 (32.3%), absent in 713 (49.1%) and unknown in 273 patients (18.7%). Paternal history of DM was positive in 255 (17.6%), negative in 927 (63.8%) and unknown in 235 patients (16.1%). The frequency of microvascular chronic complications in patients with and without a positive maternal history of DM was similar: diabetic nephropathy (51.5 vs 52.5%), diabetic retinopathy (46.0 vs 41.7%), and diabetic sensory neuropathy (31.0 vs 37.1%). The prevalence of macrovascular chronic complications and MetS was also similar. Patients with type 2 DM were more likely to have a maternal than a paternal history of DM, although maternal history of DM was not associated with an increased prevalence of chronic complications or MetS.

Effect of metabolic syndrome and of its individual components on renal function of patients with type 2 diabetes mellitus

The objective of this study was to evaluate the effect of metabolic syndrome (MetS) and its individual components on the renal function of patients with type 2 diabetes mellitus (DM). A cross-sectional study was performed in 842 type 2 DM patients. A clinical and laboratory evaluation, including estimated glomerular filtration rate (eGFR) calculated by the modification of diet in renal disease formula, was performed. MetS was defined according to National Cholesterol Education Program - Adult Treatment Panel III criteria. Mean patient age was 57.9 ± 10.1 years and 313 (37.2%) patients were males. MetS was detected in 662 (78.6%) patients. A progressive reduction in eGFR was observed as the number of individual MetS components increased (one: 98.2 ± 30.8; two: 92.9 ± 28.1; three: 84.0 ± 25.1; four: 83.8 ± 28.5, and five: 79.0 ± 23.0; P < 0.001). MetS increased the risk for low eGFR (<60 mL·min-1·1.73 (m²)-1) 2.82-fold (95%CI = 1.55-5.12, P < 0.001). Hypertension (OR = 2.2, 95%CI = 1.39-3.49, P = 0.001) and hypertriglyceridemia (OR = 1.62, 95%CI = 1.19-2.20, P = 0.002) were the individual components with the strongest associations with low eGFR. In conclusion, there is an association between MetS and the reduction of eGFR in patients with type 2 DM, with hypertension and hypertriglyceridemia being the most important contributors in this sample. Interventional studies should be conducted to determine if treatment of MetS can prevent renal failure in type 2 DM patients.

Maternal serum progesterone, estradiol and estriol levels in successful dinoprostone-induced labor

Hormone-mediated quiescence involves the maintenance of a decreased inflammatory responsiveness. However, no study has investigated whether labor induction with prostanoids is associated with changes in the levels of maternal serum hormones. The objective of this study was to determine whether labor induction with dinoprostone is associated with changes in maternal serum progesterone, estradiol, and estriol levels. Blood samples were obtained from 81 pregnant women at term. Sixteen patients had vaginal birth after spontaneous labor, 12 required cesarean section after spontaneous labor and 16 underwent elective cesarean. Thirty-seven patients had labor induction with dinoprostone. Eligible patients received a vaginal insert of dinoprostone (10 mg) and were followed until delivery. Serum progesterone (P4), estradiol (E2) and estriol (E3) levels and changes in P4/E2, P4/E3 and E3/E2 ratios were monitored from admission to immediately before birth, and the association of these measures with the resulting clinical classification outcome (route of delivery and induction responsiveness) was assessed. Progesterone levels decreased from admission to birth in patients who underwent successful labor induction with dinoprostone [vaginal and cesarean birth after induced labor: 23% (P < 0.001) and 18% (P < 0.025) decrease, respectively], but not in those whose induction failed (6.4% decrease, P > 0.05). Estriol and estradiol levels, P4/E2, P4/E3 and E3/E2 ratios did not differ between groups. Successful dinoprostone-induced labor was associated with reduced maternal progesterone levels from induction to birth. While a causal relationship between progesterone decrease and effective dinoprostone-induced labor cannot be established, it is tempting to propose that dinoprostone may contribute to progesterone withdrawal and favor labor induction in humans.

Caryocar brasiliense camb protects against genomic and oxidative damage in urethane-induced lung carcinogenesis

The antioxidant effects of Caryocar brasiliense Camb, commonly known as the pequi fruit, have not been evaluated to determine their protective effects against oxidative damage in lung carcinogenesis. In the present study, we evaluated the role of pequi fruit against urethane-induced DNA damage and oxidative stress in forty 8-12 week old male BALB/C mice. An in vivo comet assay was performed to assess DNA damage in lung tissues and changes in lipid peroxidation and redox cycle antioxidants were monitored for oxidative stress. Prior supplementation with pequi oil or its extract (15 µL, 60 days) significantly reduced urethane-induced oxidative stress. A protective effect against DNA damage was associated with the modulation of lipid peroxidation and low protein and gene expression of nitric oxide synthase. These findings suggest that the intake of pequi fruit might protect against in vivo genotoxicity and oxidative stress.

Optical coherence tomography imaging of the basal ganglia: feasibility and brief review

Optical coherence tomography (OCT) is a promising medical imaging technique that uses light to capture real-time cross-sectional images from biological tissues in micrometer resolution. Commercially available optical coherence tomography systems are employed in diverse applications, including art conservation and diagnostic medicine, notably in cardiology and ophthalmology. Application of this technology in the brain may enable distinction between white matter and gray matter, and obtainment of detailed images from within the encephalon. We present, herein, the in vivo implementation of OCT imaging in the rat brain striatum. For this, two male 60-day-old rats (Rattus norvegicus, Albinus variation, Wistar) were stereotactically implanted with guide cannulas into the striatum to guide a 2.7-French diameter high-definition OCT imaging catheter (Dragonfly™, St. Jude Medical, USA). Obtained images were compared with corresponding histologically stained sections to collect imaging samples. A brief analysis of OCT technology and its current applications is also reported, as well as intra-cerebral OCT feasibility on brain mapping during neurosurgical procedures.

Avaliação das propriedades físicas, químicas e sensorial de preferência de goiabas em calda industrializadas

Quatro marcas de goiabas em calda foram submetidas a análises físico-químicas, de cor e textura instrumentais e teste sensorial de preferência, a fim de avaliar as diferenças entre os produtos comerciais. As mesmas análises foram efetuadas em uma goiaba in natura madura, a fim de avaliar os possíveis efeitos do processamento na qualidade do produto. De maneira geral, observou-se grandes diferenças entre os produtos das diferentes marcas, e muitas vezes entre os frutos de um mesmo fabricante. As análises químicas mostraram que o teor de açúcares da maior parte dos produtos está entre 22 e 30%, com exceção de uma amostra que mostrou um valor bem mais elevado (ao redor de 40%). A análise sensorial mostrou que esta amostra com maior teor de açúcares foi a mais preferida em relação à doçura. Na análise de cor foram observados menores valores de a* em relação à fruta in natura, possivelmente devido à degradação dos carotenóides da goiaba. A luminosidade das goiabas em calda também é maior que da fruta in natura, devido à presença dos açúcares. Esta entrada de açúcares na fruta junto com o processamento térmico utilizado pode ter causado possível gelificação da pectina, aumentando a dureza, firmeza e elasticidade de algumas amostras processadas, quando comparadas à fruta fresca. No entanto, em alguns casos foi visível o efeito de processamentos mais drásticos, que levaram à perda da estrutura celular, observada pelos baixos valores das propriedades mecânicas. Em relação à textura e aparência, a amostra mais dura foi a preferida.