Enhanced expression of Ang-(1-7) during pregnancy

Pregnancy is a physiological condition characterized by a progressive increase of the different components of the renin-angiotensin system (RAS). The physiological consequences of the stimulated RAS in normal pregnancy are incompletely understood, and even less understood is the question of how this system may be altered and contribute to the hypertensive disorders of pregnancy. Findings from our group have provided novel insights into how the RAS may contribute to the physiological condition of pregnancy by showing that pregnancy increases the expression of both the vasodilator heptapeptide of the RAS, angiotensin-(1-7) [Ang-(1-7)], and of a newly cloned angiotensin converting enzyme (ACE) homolog, ACE2, that shows high catalytic efficiency for Ang II metabolism to Ang-(1-7). The discovery of ACE2 adds a new dimension to the complexity of the RAS by providing a new arm that may counter-regulate the activity of the vasoconstrictor component, while amplifying the vasodilator component. The studies reviewed in this article demonstrate that Ang-(1-7) increases in plasma and urine of normal pregnant women. In preeclamptic subjects we showed that plasma Ang-(1-7) was suppressed as compared to the levels found in normal pregnancy. In addition, kidney and urinary levels of Ang-(1-7) were increased in pregnant rats coinciding with the enhanced detection and expression of ACE2. These findings support the concept that in normal pregnancy enhanced ACE2 may counteract the elevation in tissue and circulating Ang II by increasing the rate of conversion to Ang-(1-7). These findings provide a basis for the physiological role of Ang-(1-7) and ACE2 during pregnancy.

Relationship between the prevalence of anti-glutamic acid decarboxylase autoantibodies and duration of type 1 diabetes mellitus in Brazilian patients

The objective of the present study was to determine whether the duration of disease has any influence on the prevalence of glutamic acid decarboxylase autoantibodies (GADA) in Brazilian patients with type 1 diabetes (T1D) and variable disease duration. We evaluated 83 patients with T1D. All participants were interviewed and blood was obtained for GADA measurement by a commercial radioimmunoassay (RSR Limited, Cardiff, UK). Four groups of patients were established according to disease duration: A) 1-5 years of disease (N = 24), B) 6-10 years of disease (N = 19), C) 11-15 years of disease (N = 25), and D) >15 years of disease (N = 15). GADA prevalence and its titers were determined in each group. GADA was positive in 38 patients (45.8%) and its frequency did not differ between the groups. The prevalence was 11/24 (45.8%), 8/19 (42.1%), 13/25 (52%), and 6/15 (40%) in groups A, B, C, and D, respectively (P = 0.874). Mean GADA titer was 12.54 ± 11.33 U/ml for the sample as a whole and 11.95 ± 11.8, 12.85 ± 12.07, 10.57 ± 8.35, and 17.45 ± 16.1 U/ml for groups A, B, C, and D, respectively (P = 0.686). Sex, age at diagnosis or ethnic background had no significant effect on GADA (+) frequency. In conclusion, in this transversal study, duration of disease did not affect significantly the prevalence of GADA or its titers in patients with T1D after one year of diagnosis. This was the first study to report this finding in the Brazilian population.

The reliability of the Brazilian version of the Composite International Diagnostic Interview (CIDI 2.1)

The objective of the present study was to determine the reliability of the Brazilian version of the Composite International Diagnostic Interview 2.1 (CIDI 2.1) in clinical psychiatry. The CIDI 2.1 was translated into Portuguese using WHO guidelines and reliability was studied using the inter-rater reliability method. The study sample consisted of 186 subjects from psychiatric hospitals and clinics, primary care centers and community services. The interviewers consisted of a group of 13 lay and three non-lay interviewers submitted to the CIDI training. The average interview time was 2 h and 30 min. General reliability ranged from kappa 0.50 to 1. For lifetime diagnoses the reliability ranged from kappa 0.77 (Bipolar Affective Disorder) to 1 (Substance-Related Disorder, Alcohol-Related Disorder, Eating Disorders). Previous year reliability ranged from kappa 0.66 (Obsessive-Compulsive Disorder) to 1 (Dissociative Disorders, Maniac Disorders, Eating Disorders). The poorest reliability rate was found for Mild Depressive Episode (kappa = 0.50) during the previous year. Training proved to be a fundamental factor for maintaining good reliability. Technical knowledge of the questionnaire compensated for the lack of psychiatric knowledge of the lay personnel. Inter-rater reliability was good to excellent for persons in psychiatric practice.

Hereditary motor and autonomic neuronopathy 1 maps to chromosome 20q13.2-13.3

The spinal muscular atrophies (SMA) or hereditary motor neuronopathies result from the continuous degeneration and death of spinal cord lower motor neurons, leading to progressive muscular weakness and atrophy. We describe a large Brazilian family exhibiting an extremely rare, late-onset, dominant, proximal, and progressive SMA accompanied by very unusual manifestations, such as an abnormal sweating pattern, and gastrointestinal and sexual dysfunctions, suggesting concomitant involvement of the autonomic nervous system. We propose a new disease category for this disorder, `hereditary motor and autonomic neuronopathy', and attribute the term, `survival of motor and autonomic neurons 1' (SMAN1) to the respective locus that was mapped to a 14.5 cM region on chromosome 20q13.2-13.3 by genetic linkage analysis and haplotype studies using microsatellite polymorphic markers. This locus lies between markers D20S120 and D20S173 showing a maximum LOD score of 4.6 at D20S171, defining a region with 33 known genes, including several potential candidates. Identifying the SMAN1 gene should not only improve our understanding of the molecular mechanisms underlying lower motor neuron diseases but also help to clarify the relationship between motor and autonomic neurons.

Effects of chronic ethanol treatment on monoamine levels in rat hippocampus and striatum

We studied the effects of ethanol on concentrations of noradrenaline (NE), dopamine (DA) and serotonin (5-HT) and their metabolites in rat hippocampus and striatum. Ethanol (2 or 4 g/kg, po, from a 20% aqueous solution) was administered daily to male Wistar rats (4-13 per group) for 30 days and animals were sacrificed 30 min or 48 h after the last administration. Monoamines were measured by HPLC and considered significant at P < 0.05. A 47% increase in 5-HT levels was observed in the hippocampus with 4 g/kg ethanol in the 30-min protocol. Ethanol (2 and 4 g/kg) decreased DA (2114.5 ± 126.4 and 1785.1 ± 234.2 ng/g wet tissue, respectively) and 3,4-dihydroxyphenylacetic acid (DOPAC, 1477.6 ± 132.1 and 1218.8 ± 271.7 ng/g wet tissue, respectively) levels, while the higher dose also decreased NE (159.8 ± 13.5), 5-HT (228.0 ± 46.8) and 5-hydroxy-3-indoleacetic acid (5-HIAA, 304.4 ± 37.2 ng/g wet tissue), in the striatum after a 48-h withdrawal as compared to controls (DA: 3063.9 ± 321.3; DOPAC: 2379.6 ± 256.0; NE: 292.8 ± 50.2; 5-HT: 412.4 ± 36.2; 5-HIAA: 703.9 ± 61.4 ng/g wet tissue). In the 30-min protocol, ethanol (2 or 4 g/kg) decreased striatal NE (66 and 70%) and DA (50 and 36%) levels. On the other hand, increases were seen in 5-HIAA (146 and 153%) and 5-HT (59 and 86%) levels. Ethanol (2 g/kg, po) increased the homovanillic acid (HVA)/DA ratio (129%) in the striatum in the 30-min protocol, while at the higher dose it increased the HVA/DA ratio in the 48-h protocol (61%). These results indicate alterations in monoamines, mainly in the striatum, after chronic ethanol, which are influenced by dose and by the length of time after the last drug administration.

A cost-effective melting temperature assay for the detection of single-nucleotide polymorphism in the MBL2 gene of HIV-1-infected children

We report a fast (less than 3 h) and cost-effective melting temperature assay method for the detection of single-nucleotide polymorphisms in the MBL2 gene. The protocol, which is based on the Corbett Rotor Gene real time PCR platform and SYBR Green I chemistry, yielded, in the cohorts studied, sensitive (100%) and specific (100%) PCR amplification without the use of costly fluorophore-labeled probes or post-PCR manipulation. At the end of the PCR, the dissociation protocol included a slow heating from 60º to 95ºC in 0.2ºC steps, with an 8-s interval between steps. Melting curve profiles were obtained using the dissociation software of the Rotor Gene-3000 apparatus. Samples were analyzed in duplicate and in different PCR runs to test the reproducibility of this technique. No supplementary data handling is required to determine the MBL2 genotype. MBL2 genotyping performed on a cohort of 164 HIV-1-positive Brazilian children and 150 healthy controls, matched for age and sex and ethnic origin, yielded reproducible results confirmed by direct sequencing of the amplicon performed in blind. The three MBL2 variants (Arg52Cys, Gly54Asp, Gly57Glu) were grouped together and called allele 0, while the combination of three wild-type alleles was called allele A. The frequency of the A/A homozygotes was significantly higher among healthy controls (0.68) than in HIV-infected children (0.55; P = 0.0234) and the frequency of MBL2 0/0 homozygotes was higher among HIV-1-infected children than healthy controls (P = 0.0296). The 0 allele was significantly more frequent among the 164 HIV-1-infected children (0.29) than among the 150 healthy controls (0.18; P = 0.0032). Our data confirm the association between the presence of the mutated MBL2 allele (allele 0) and HIV-1 infection in perinatally exposed children. Our results are in agreement with the literature data which indicate that the presence of the allele 0 confers a relative risk of 1.37 for HIV-1 infection through vertical transmission.

Meditationes sancti evangelii 37

Invokaatio: Deo duce.

Meditationes sanctarum epistolarum 37

Invokaatio: Deo duce.

Fish oil ingestion reduces the number of aberrant crypt foci and adenoma in 1,2-dimethylhydrazine-induced colon cancer in rats

We determined the effect of fish oil (FO) ingestion on colonic carcinogenesis in rats. Male Wistar rats received 4 subcutaneous injections (40 mg/kg body weight each) of 1,2-dimethylhydrazine (DMH) at 3-day intervals and were fed a diet containing 18% by weight FO (N = 10) or soybean oil (SO, N = 10) for 36 weeks. At sacrifice, the colon was removed, aberrant crypt foci were counted and the fatty acid profile was determined. Intestinal tumors were removed and classified as adenoma or carcinoma. Liver and feces were collected and analyzed for fatty acid profile. FO reduced the mean (± SEM) number of aberrant crypt foci compared to SO (113.55 ± 6.97 vs 214.60 ± 18.61; P < 0.05) and the incidence of adenoma (FO: 20% vs SO: 100%), but carcinoma occurred equally in FO and SO rats (2 animals per group). The polyunsaturated fatty acid (PUFA) profile of the colon was affected by diet (P < 0.05): total ω-3 (FO: 8.18 ± 0.97 vs SO: 1.71 ± 0.54%) and total ω-6 (FO: 3.83 ± 0.59 vs SO: 10.43 ± 1.28%). The same occurred in the liver (P < 0.05): total ω-3 (FO: 34.41 ± 2.6 vs SO: 6.46 ± 0.59%) and total ω-6 (FO: 8.73 ± 1.37 vs SO: 42.12 ± 2.33%). The PUFA profile of the feces and liver polyamine levels did not differ between groups (P > 0.05). In conclusion, our findings indicate that chronic FO ingestion protected against the DMH-induced preneoplastic colon lesions and adenoma development, but not against carcinoma in rats.

Glomerular damage as a predictor of renal allograft loss

Interstitial fibrosis and tubular atrophy (IF/TA) are the most common cause of renal graft failure. Chronic transplant glomerulopathy (CTG) is present in approximately 1.5-3.0% of all renal grafts. We retrospectively studied the contribution of CTG and recurrent post-transplant glomerulopathies (RGN) to graft loss. We analyzed 123 patients with chronic renal allograft dysfunction and divided them into three groups: CTG (N = 37), RGN (N = 21), and IF/TA (N = 65). Demographic data were analyzed and the variables related to graft function identified by statistical methods. CTG had a significantly lower allograft survival than IF/TA. In a multivariate analysis, protective factors for allograft outcomes were: use of angiotensin-converting enzyme inhibitor (ACEI; hazard ratio (HR) = 0.12, P = 0.001), mycophenolate mofetil (MMF; HR = 0.17, P = 0.026), hepatitis C virus (HR = 7.29, P = 0.003), delayed graft function (HR = 5.32, P = 0.016), serum creatinine ≥1.5 mg/dL at the 1st year post-transplant (HR = 0.20, P = 0.011), and proteinuria ≥0.5 g/24 h at the 1st year post-transplant (HR = 0.14, P = 0.004). The presence of glomerular damage is a risk factor for allograft loss (HR = 4.55, P = 0.015). The presence of some degree of chronic glomerular damage in addition to the diagnosis of IF/TA was the most important risk factor associated with allograft loss since it could indicate chronic active antibody-mediated rejection. ACEI and MMF were associated with better outcomes, indicating that they might improve graft survival.

In titulos libri 37-40 Corporis juris civilis Romani

Variantti A.

Chronicon episcoporum Finlandensium 37

Arkit: 1 arkintunnukseton lehti, 4D-4E4.

In titulos libri 37-40 Corporis juris civilis Romani

Variantti B.