Functional mapping of the cardiorespiratory effects of dorsal and median raphe nuclei in the rat

The dorsal (DRN) and median (MRN) raphe nuclei are important sources of serotonergic innervation to the forebrain, projecting to sites involved in cardiovascular regulation. These nuclei have been mapped using electrical stimulation, which has the limitation of stimulating fibers of passage. The present study maps these areas with chemical stimulation, investigating their influence on cardiorespiratory parameters. Urethane-anesthetized (1.2 g/kg, iv) male Wistar rats (280-300 g) were instrumented for pulsatile and mean blood pressure (MBP), heart rate, renal nerve activity, and respiratory frequency recordings. Microinjections of L-glutamate (0.18 M, 50-100 nl with 1% Pontamine Sky Blue) were performed within the DRN or the MRN with glass micropipettes. At the end of the experiments the sites of microinjection were identified. The majority of sites within the MRN (86.1%) and DRN (85.4%) evoked pressor responses when stimulated (DRN: deltaMBP = +14.7 ± 1.2; MRN: deltaMBP = +13.6 ± 1.3 mmHg). The changes in renal nerve activity and respiratory rate caused by L-glutamate were +45 ± 11 and +42 ± 9% (DRN; P < 0.05%), +40 ± 10 and +29 ± 7% (MRN, P < 0.05), respectively. No significant changes were observed in saline-microinjected animals. This study shows that: a) the blood pressure increases previously observed by electrical stimulation within the raphe are due to activation of local neurons, b) this pressor effect is due to sympathoexcitation because the stimulation increased renal sympathetic activity but did not produce tachycardia, and c) the stimulation of cell bodies in these nuclei also increases the respiratory rate.

Frequency of CCR5delta32 in Brazilian populations

A sample of 103 randomly chosen healthy individuals from Alegrete, RS, Brazil, was tested for the CCR5delta32 allele, which is known to influence susceptibility to HIV-1 infection. The CCR5delta32 allele was identified by PCR amplification using specific primers flanking the region of deletion, followed by electrophoresis on a 3% agarose gel. The data obtained were compared to those reported for other populations and interpreted in terms of Brazilian history. The individuals studied came from a highly admixed population. Most of them were identified as white (N = 59), while blacks and browns (mulattoes) were N = 13 and N = 31, respectively. The observed frequencies, considering the white, black and brown samples (6.8, 3.8, and 6.4%, respectively), suggest an important European parental contribution, even in populations identified as black and brown. However, in Brazil as a whole, this allele shows gradients indicating a relatively good correlation with the classification based on skin color and other physical traits, used here to define major Brazilian population groups.

Mesopic radial frequency contrast sensitivity function for young and older adults

The objective of the present study was to determine contrast sensitivity curves of concentric circular patterns with radial frequencies of 0.25, 0.5, 1.0, 2.0, and 4.0 cycles per degree in young and older adult volunteers. These parameters were also compared with sensitivity contrasts for sine-wave gratings. All participants had normal acuity vision and were free of identifiable ocular illness. Contrast sensitivity was measured in 6 young adults aged 19 to 23 years and 6 older adults aged 60 to 69 years using the psychophysical forced-choice method. In this paradigm the volunteers had to decide which of two stimuli contained the above radial frequencies at low contrast levels. The other neutral stimulus was gray with homogeneous luminance. We detected a decline in contrast sensitivity for older adults at all radial frequencies compared to young adults. Also, contrast sensitivity for sine-wave gratings at all measured frequencies was better, as predicted, for all young adults. Maximum sensitivities in the radial frequency contrast sensitivity function and contrast sensitivity function occurred at 0.25 and 0.5 cycles per degree, respectively, for both young and older adults. These results suggest age-related changes in the contrast sensitivity function for concentric symmetrical stimuli.

High frequency of mutation G377S in Brazilian type 3 Gaucher disease patients

Gaucher disease (GD), the most prevalent lysosome storage disorder, presents an autosomal recessive mode of inheritance. It is a paradigm for therapeutic intervention in medical genetics due to the existence of effective enzyme replacement therapy. We report here the analysis of GD in 262 unrelated Brazilian patients, carried out in order to establish the frequency of the most common mutations and to provide prognostic information based on genotype-phenotype correlations. Among 247 type 1 GD patients, mutation N370S was detected in 47% of all the alleles, but N370S/N370S homozygosity was found in only 10% of the patients, a much lower frequency than expected, suggesting that most individuals presenting this genotype may not receive medical attention. Recombinant alleles were detected at a high frequency: 44% of the chromosomes bearing mutation L444P had other mutations derived from the pseudogene sequence, present in 25% of patients. Three neuronopathic type 2 patients were homozygous for L444P, all presenting additional mutations (E326K or recombinant alleles) that probably lead to the more severe phenotypes. Six children, classified as type 1 GD patients, had a L444P/L444P genotype, showing that neuronopathic symptoms may only manifest later in life. This would indicate the need for a higher treatment dose during enzyme replacement therapy. Finally, mutation G377S was present in 4 homozygous type 1 patients and also in compound heterozygosity in 5 (42%) type 3 patients. These findings indicate that G377S cannot be unambiguously classified as mild and suggest an allele-dose effect for this mutation.

Relative frequency, clinical, neuroimaging, and postsurgical features of pediatric temporal lobe epilepsy

We describe the relative frequency, clinical features, neuroimaging and pathological results, and outcome after pharmacological or surgical intervention for a series of pediatric patients with temporal lobe epilepsy (TLE) from an epilepsy center in Brazil. The medical records of children younger than 12 years with features strongly suggestive of TLE were reviewed from January 1999 to June 1999. Selected children were evaluated regarding clinical, EEG, and magnetic resonance imaging (MRI) investigation and divided into three groups according to MRI: group 1 (G1, N = 9), patients with hippocampal atrophy; group 2 (G2, N = 10), patients with normal MRI, and group 3 (G3, N = 12), patients with other specific temporal lesions. A review of 1732 records of children with epilepsy revealed 31 cases with TLE (relative frequency of 1.79%). However, when the investigation was narrowed to cases with intractable seizures that needed video-EEG monitoring (N = 68) or epilepsy surgery (N = 32), the relative frequency of TLE increased to 19.11 (13/68) and 31.25% (10/32), respectively. At the beginning of the study, 25 of 31 patients had a high seizure frequency (80.6%), which declined to 11 of 31 (35.5%) at the conclusion of the study, as a consequence of pharmacological and/or surgical therapy. This improvement in seizure control was significant in G1 (P < 0.05) and G3 (P < 0.01) mainly due to good postsurgical outcome, and was not significant in G2 (P > 0.1, McNemar's test). These results indicate that the relative frequency of TLE in children was low, but increased considerably among cases with pharmacoresistant seizures. Patients with specific lesions were likely to undergo surgery, with good postoperative outcomes.

The effect of an aerobic training program on the electrical remodeling of the heart: high-frequency components of the signal-averaged electrocardiogram are predictors of the maximal aerobic power

Increased heart rate variability (HRV) and high-frequency content of the terminal region of the ventricular activation of signal-averaged ECG (SAECG) have been reported in athletes. The present study investigates HRV and SAECG parameters as predictors of maximal aerobic power (VO2max) in athletes. HRV, SAECG and VO2max were determined in 18 high-performance long-distance (25 ± 6 years; 17 males) runners 24 h after a training session. Clinical visits, ECG and VO2max determination were scheduled for all athletes during thew training period. A group of 18 untrained healthy volunteers matched for age, gender, and body surface area was included as controls. SAECG was acquired in the resting supine position for 15 min and processed to extract average RR interval (Mean-RR) and root mean squared standard deviation (RMSSD) of the difference of two consecutive normal RR intervals. SAECG variables analyzed in the vector magnitude with 40-250 Hz band-pass bi-directional filtering were: total and 40-µV terminal (LAS40) duration of ventricular activation, RMS voltage of total (RMST) and of the 40-ms terminal region of ventricular activation. Linear and multivariate stepwise logistic regressions oriented by inter-group comparisons were adjusted in significant variables in order to predict VO2max, with a P < 0.05 considered to be significant. VO2max correlated significantly (P < 0.05) with RMST (r = 0.77), Mean-RR (r = 0.62), RMSSD (r = 0.47), and LAS40 (r = -0.39). RMST was the independent predictor of VO2max. In athletes, HRV and high-frequency components of the SAECG correlate with VO2max and the high-frequency content of SAECG is an independent predictor of VO2max.

Low occurrence of occult hepatitis B virus infection and high frequency of hepatitis C virus genotype 3 in hepatocellular carcinoma in Brazil

Occult hepatitis B virus (HBV) infection has been reported among patients with hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC). Our aim was to evaluate the presence of occult HBV infection in patients with HCV-related liver cirrhosis (LC) with or without HCC in São Paulo, Brazil. Serum and liver tissue samples from 50 hepatitis B surface antigen-negative patients with HCV-related LC who underwent liver transplantation at the University of São Paulo School of Medicine Hospital from 1993 to 2004 were divided into groups with LC only (N = 33) and with LC plus HCC (N = 17). HBV DNA was assayed for serum and paraffin-embedded liver tissue (tumoral and non-tumoral) using real time PCR and only 1 case with HCC had HBV DNA-positive serum. All liver samples were negative. HCV genotype 3 was detected in 17/39 (43.7%) cases. In conclusion, using a sensitive real time PCR directed to detect HBV variants circulating in Brazil, occult hepatitis B infection was not found among HCV-positive cirrhotic patients and was rarely found among HCV-positive HCC patients. These results are probably related to the low prevalence of HBV infection in our population. Furthermore, we have also shown that HCV genotype 3 is frequently found in Brazilian cirrhotic patients, particularly when they also have HCC. More studies involving a large number of cases should be carried out to confirm these data and to further characterize Brazilian HCV genotype isolates to elucidate genetic features that might be related to its carcinogenic potential.

Comparison of the Polar S810i monitor and the ECG for the analysis of heart rate variability in the time and frequency domains

The aim of the present study was to compare heart rate variability (HRV) at rest and during exercise using a temporal series obtained with the Polar S810i monitor and a signal from a LYNX® signal conditioner (BIO EMG 1000 model) with a channel configured for the acquisition of ECG signals. Fifteen healthy subjects aged 20.9 ± 1.4 years were analyzed. The subjects remained at rest for 20 min and performed exercise for another 20 min with the workload selected to achieve 60% of submaximal heart rate. RR series were obtained for each individual with a Polar S810i instrument and with an ECG analyzed with a biological signal conditioner. The HRV indices (rMSSD, pNN50, LFnu, HFnu, and LF/HF) were calculated after signal processing and analysis. The unpaired Student t-test and intraclass correlation coefficient were used for data analysis. No statistically significant differences were observed when comparing the values analyzed by means of the two devices for HRV at rest and during exercise. The intraclass correlation coefficient demonstrated satisfactory correlation between the values obtained by the devices at rest (pNN50 = 0.994; rMSSD = 0.995; LFnu = 0.978; HFnu = 0.978; LF/HF = 0.982) and during exercise (pNN50 = 0.869; rMSSD = 0.929; LFnu = 0.973; HFnu = 0.973; LF/HF = 0.942). The calculation of HRV values by means of temporal series obtained from the Polar S810i instrument appears to be as reliable as those obtained by processing the ECG signal captured with a signal conditioner.

Breathing pattern and thoracoabdominal motion during exercise in chronic obstructive pulmonary disease

Subjects with chronic obstructive pulmonary disease (COPD) present breathing pattern and thoracoabdominal motion abnormalities that may contribute to exercise limitation. Twenty-two men with stable COPD (FEV1 = 42.6 ± 13.5% predicted; age 68 ± 8 years; mean ± SD) on usual medication and with at least 5 years of diagnosis were evaluated at rest and during an incremental cycle exercise test (10 watts/2 min). Changes in respiratory frequency, tidal volume, rib cage and abdominal motion contribution to tidal volume and the phase angle that measures the asynchrony were analyzed by inductive respiratory plethysmography at rest and during three levels of exercise (30-50, 70-80, and 100% maximal work load). Repeated measures ANOVA followed by pre-planned contrasts and Bonferroni corrections were used for analyses. As expected, the greater the exercise intensity the higher the tidal volume and respiratory frequency. Abdominal motion contributed to the tidal volume increase (rest: 49.82 ± 11.19% vs exercise: 64.15 ± 9.7%, 63.41 ± 10%, and 65.56 ± 10.2%, respectively, P < 0.001) as well as the asynchrony [phase angle: 11.95 ± 7.24° at rest vs 22.2 ± 15° (P = 0.002), 22.6 ± 9° (P < 0.001), and 22.7 ± 8° (P < 0.001), respectively, at the three levels of exercise]. In conclusion, the increase in ventilation during exercise in COPD patients was associated with the major motion of the abdominal compartment and with an increase in the asynchrony independent of exercise intensity. It suggests that cycling exercise is an effective way of enhancing ventilation in COPD patients.

Low-frequency fatigue at maximal and submaximal muscle contractions

Skeletal muscle force production following repetitive contractions is preferentially reduced when muscle is evaluated with low-frequency stimulation. This selective impairment in force generation is called low-frequency fatigue (LFF) and could be dependent on the contraction type. The purpose of this study was to compare LFF after concentric and eccentric maximal and submaximal contractions of knee extensor muscles. Ten healthy male subjects (age: 23.6 ± 4.2 years; weight: 73.8 ± 7.7 kg; height: 1.79 ± 0.05 m) executed maximal voluntary contractions that were measured before a fatigue test (pre-exercise), immediately after (after-exercise) and after 1 h of recovery (after-recovery). The fatigue test consisted of 60 maximal (100%) or submaximal (40%) dynamic concentric or eccentric knee extensions at an angular velocity of 60°/s. The isometric torque produced by low- (20 Hz) and high- (100 Hz) frequency stimulation was also measured at these times and the 20:100 Hz ratio was calculated to assess LFF. One-way ANOVA for repeated measures followed by the Newman-Keuls post hoc test was used to determine significant (P < 0.05) differences. LFF was evident after-recovery in all trials except following submaximal eccentric contractions. LFF was not evident after-exercise, regardless of exercise intensity or contraction type. Our results suggest that low-frequency fatigue was evident after submaximal concentric but not submaximal eccentric contractions and was more pronounced after 1-h of recovery.

Estimation procedures affect the center of pressure frequency analysis

Even though frequency analysis of body sway is widely applied in clinical studies, the lack of standardized procedures concerning power spectrum estimation may provide unreliable descriptors. Stabilometric tests were applied to 35 subjects (20-51 years, 54-95 kg, 1.6-1.9 m) and the power spectral density function was estimated for the anterior-posterior center of pressure time series. The median frequency was compared between power spectra estimated according to signal partitioning, sampling rate, test duration, and detrending methods. The median frequency reliability for different test durations was assessed using the intraclass correlation coefficient. When increasing number of segments, shortening test duration or applying linear detrending, the median frequency values increased significantly up to 137%. Even the shortest test duration provided reliable estimates as observed with the intraclass coefficient (0.74-0.89 confidence interval for a single 20-s test). Clinical assessment of balance may benefit from a standardized protocol for center of pressure spectral analysis that provides an adequate relationship between resolution and variance. An algorithm to estimate center of pressure power density spectrum is also proposed.

Effect of frequency of static stretching on flexibility, hamstring tightness and electromyographic activity

We compared the effect of the number of weekly repetitions of a static stretching program on the flexibility, hamstring tightness and electromyographic activity of the hamstring and of the triceps surae muscles. Thirty-one healthy subjects with hamstring tightness, defined as the inability to perform total knee extension, and shortened triceps surae, defined by a tibiotarsal angle wider than 90° during trunk flexion, were divided into three groups: G1 performed the stretching exercises once a week; G2, three times a week, and G3, five times a week. The parameters were determined before and after the stretching program. Flexibility improved in all groups after intervention, from 7.65 ± 10.38 to 3.67 ± 12.08 in G1, from 10.73 ± 12.07 to 0.77 ± 10.45 in G2, and from 14.20 ± 10.75 to 6.85 ± 12.19 cm in G3 (P < 0.05 for all comparisons). The increase in flexibility was higher in G2 than in G1 (P = 0.018), while G2 and G3 showed no significant difference (G1: 4 ± 2.17, G2: 10 ± 5.27; G3: 7.5 ± 4.77 cm). Hamstring tightness improved in all groups, from 37.90 ± 6.44 to 29 ± 11.65 in G1, from 39.82 ± 9.63 to 21.91 ± 8.40 in G2, and from 37.20 ± 6.63 to 26.10 ± 5.72° in G3 (P < 0.05 for all comparisons). During stretching, a statistically significant difference was observed in electromyographic activity of biceps femoris muscle between G1 and G3 (P = 0.048) and G2 and G3 (P = 0.0009). No significant differences were found in electromyographic activity during maximal isometric contraction. Stretching exercises performed three times a week were sufficient to improve flexibility and range of motion compared to subjects exercising once a week, with results similar to those of subjects who exercised five times a week.

Frequency of 8 CFTR gene mutations in cystic fibrosis patients in Minas Gerais, Brazil, diagnosed by neonatal screening

The nature and frequency of cystic fibrosis mutations in Brazil is not uniform due to the highly varied ethnic composition of the population. The average frequency of the F508del mutation has been reported to be 48.6%. Other common mutations in Brazil are G542X, R1162X, and N1303K. The aim of this study was to analyze the frequency of 8 mutations (F508del, G542X, R1162X, N1303K, W1282X, G85E, 3120+1G>A, and 711+1G>T) in a sample of 111 newborn patients with cystic fibrosis diagnosed by the Cystic Fibrosis Neonatal Screening Program of Minas Gerais State. The mutations were tested by allele-specific oligonucleotide PCR with specially designed primers. An allele frequency of 48.2% was observed for the F508del mutation, and allele frequencies of 5.41, 4.50, 4.05, and 3.60% were found for the R1162X, G542X, 3120+1G>A, and G85E mutations, respectively. The genotypes obtained were in Hardy-Weinberg equilibrium. These data demonstrate that the 8-mutation panel studied here has extensive coverage (68%) for the cystic fibrosis mutations in Minas Gerais. These data improve our knowledge of cystic fibrosis in Brazil, particularly in this region. In addition, this investigation contributed to the establishment of a sensitive and population-specific mutation panel, which can be helpful for molecular diagnosis of cystic fibrosis.

Acute kidney injury in AIDS: frequency, RIFLE classification and outcome

The objective of the present study was to evaluate the characteristics of acute kidney injury (AKI) in AIDS patients and the value of RIFLE classification for predicting outcome. The study was conducted on AIDS patients admitted to an infectious diseases hospital inBrazil. The patients with AKI were classified according to the RIFLE classification: R (risk), I (injury), F (failure), L (loss), and E (end-stage renal disease). Univariate and multivariate analyses were used to evaluate the factors associated with AKI. A total of 532 patients with a mean age of 35 ± 8.5 years were included in this study. AKI was observed in 37% of the cases. Patients were classified as "R" (18%), "I" (7.7%) and "F" (11%). Independent risk factors for AKI were thrombocytopenia (OR = 2.9, 95%CI = 1.5-5.6, P < 0.001) and elevation of aspartate aminotransferase (AST) (OR = 3.5, 95%CI = 1.8-6.6, P < 0.001). General mortality was 25.7% and was higher among patients with AKI (40.2 vs17%, P < 0.001). AKI was associated with death and mortality increased according to RIFLE classification - "R" (OR 2.4), "I" (OR 3.0) and "F" (OR 5.1), P < 0.001. AKI is a frequent complication in AIDS patients, which is associated with increased mortality. RIFLE classification is an important indicator of poor outcome for AIDS patients.

Frequency of primary glomerular disease in northeastern China

Most frequently reported Chinese renal biopsy data have originated from southeastern China. The present study analyzed the renal biopsy data from northeastern China. The records of 1550 consecutive native patients who were diagnosed with primary glomerular diseases (PGD) after renal biopsy at our hospital during 2005-2009 were used. These patients were divided into four age groups for stratified analysis: <15, 15-44, 45-59, and ≥60 years old. Among PGD, minimal change disease (MCD) was the most common histologically diagnosed disease (30.7%), followed by IgA nephropathy (IgAN), mesangial proliferative glomerulonephritis (MsPGN), membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), focal segmental glomerulosclerosis (FSGS), and endocapillary proliferative glomerulonephritis (EnPGN). MCD was the disease most frequently observed (43.7%) in the <15-year-old group. MsPGN was the most common disease in the elderly group (38.1%). MsPGN was more prevalent in females (27.8%), whereas MCD was more prevalent in males (35.3%). Primary glomerular diseases constituted the most commonly encountered group of diseases with a high prevalence of MCD, which predominantly affected males and young adults. The prevalence of MCD was high in northeastern China. Further study is necessary to expand the epidemiologic data available for renal disease in China.