Neutralizing capacity of a new monovalent anti-Bothrops atrox antivenom: comparison with two commercial antivenoms

Three horse-derived antivenoms were tested for their ability to neutralize lethal, hemorrhagic, edema-forming, defibrinating and myotoxic activities induced by the venom of Bothrops atrox from Antioquia and Chocó (Colombia). The following antivenoms were used: a) polyvalent (crotaline) antivenom produced by Instituto Clodomiro Picado (Costa Rica), b) monovalent antibothropic antivenom produced by Instituto Nacional de Salud-INS (Bogotá), and c) a new monovalent anti-B. atrox antivenom produced with the venom of B. atrox from Antioquia and Chocó. The three antivenoms neutralized all toxic activities tested albeit with different potencies. The new monovalent anti-B. atrox antivenom showed the highest neutralizing ability against edema-forming and defibrinating effects of B. atrox venom (41 ± 2 and 100 ± 32 µl antivenom/mg venom, respectively), suggesting that it should be useful in the treatment of B. atrox envenomation in Antioquia and Chocó

Pulmonary emphysema induced by passive smoking: an experimental study in rats

We describe a short time model for inducing experimental emphysema in rats by chronic tobacco smoke inhalation. Three groups of male Wistar rats (6 months old) were studied: controls (N = 8), rats intoxicated for 45 days (s-45, N = 7) or for 90 days (s-90, N = 8). The exposed animals were intoxicated 3 times a day (10 cigarettes per exposure period), 5 days a week. Pulmonary damage was assessed by means of functional tests and quantitative pathological examination of the airways and lung parenchyma. The s-45 and s-90 animals were similar in terms of functional residual capacity (FRC) corrected for body weight (FRC/kg) but both groups of smoking rats exhibited significantly higher FRC/kg values than the controls (s-45 = 6.33; s-90 = 6.46; controls = 3.78; P<0.05). When the two groups of smoking rats were pooled together and compared to controls, they showed decreased lung elastance (1.6 vs 2.19; P = 0.046) and increased mean linear intercept (Lm) (85.14 vs 66.44; P = 0.025). The s-90 animals presented higher inflammation and muscular hypertrophy at the level of the axial bronchus than the controls (P<0.05). When smoking groups were pooled and compared to controls, they presented significantly higher inflammation at the lateral level (P = 0.028), as well as airway secretory hyperplasia (P = 0.024) and smooth muscle hypertrophy (P = 0.005) at the axial level. Due to its simplicity, low cost and short duration, this technique may be a useful model to obtain new information about airspace remodeling due to chronic tobacco consumption

Differences between remaining ability and loss of capacity in maximum aerobic impairment

In the evaluation of exercise intolerance of patients with respiratory diseases the American Medical Association (AMA) and the American Thoracic Society (ATS) have proposed similar classifications for rating aerobic impairment using maximum oxygen uptake (VO2max) normalized for total body weight (ml min-1 kg-1). However, subjects with the same VO2max weight-corrected values may have considerably different losses of aerobic performance (VO2max expressed as % predicted). We have proposed a new, specific method for rating loss of aerobic capacity (VO2max, % predicted) and we have compared the two classifications in a prospective study involving 75 silicotic claimants. Logistic regression analysis showed that the disagreement between rating systems (higher dysfunction by the AMA/ATS classification) was associated with age >50 years (P<0.005) and overweight (P = 0.04). Interestingly, clinical (dyspnea score) and spirometric (FEV1) normality were only associated with the VO2max, % predicted, normal values (P<0.01); therefore, in older and obese subjects the AMA/ATS classification tended to overestimate the aerobic dysfunction. We conclude that in the evaluation of aerobic impairment in patients with respiratory diseases, the loss of aerobic capacity (VO2max, % predicted) should be used instead of the traditional method (remaining aerobic ability, VO2max, in ml min-1 kg-1).

Evaluation of electromyographic activity and heart rate responses to isometric exercise. The role played by muscular mass and type

The purpose of the present study was to examine the relationship between the electromyographic (EMG) activity and heart rate (HR) responses induced by isometric exercise performed by knee extension (KE) and flexion (KF) in men. Fifteen healthy male subjects, 21 ± 1.3 years (mean ± SD), were submitted to KE and KF isometric exercise tests at 100% of maximal voluntary contraction (MVC). The exercises were performed with one leg (right or left) and with two legs simultaneously, for 10 s in the sitting position with the hip and knee flexed at 90o. EMG activity (root mean square values) and HR (beats/min) were recorded simultaneously both at rest and throughout the sustained contraction. The HR responses to isometric exercise in KE and KF were similar when performed with one and two legs. However, the HR increase was always significantly higher in KE than KF (P<0.05), whereas the EMG activity was higher in KE than in KF (P<0.05), regardless of the muscle mass (one or two legs) involved in the effort. The correlation coefficients between HR response and the EMG activity during KE (r = 0.33, P>0.05) and KF (r = 0.15, P>0.05) contractions were not significant. These results suggest that the predominant mechanism responsible for the larger increase in HR response to KE as compared to KF in our study could be dependent on qualitative and quantitative differences in the fiber type composition found in each muscle group. This mechanism seems to demand a higher activation of motor units with a corresponding increase in central command to the cardiovascular centers that modulate HR control.

Reference values for lung function tests: III. Carbon monoxide diffusing capacity (transfer factor)

Carbon monoxide diffusing capacity (DLCO) or transfer factor (TLCO) is a particularly useful test of the appropriateness of gas exchange across the lung alveolocapillary membrane. With the purpose of establishing predictive equations for DLCO using a non-smoking sample of the adult Brazilian population, we prospectively evaluated 100 subjects (50 males and 50 females aged 20 to 80 years), randomly selected from more than 8,000 individuals. Gender-specific linear prediction equations were developed by multiple regression analysis with single breath (SB) absolute and volume-corrected (VA) DLCO values as dependent variables. In the prediction equations, age (years) and height (cm) had opposite effects on DLCOSB (ml min-1 mmHg-1), independent of gender (-0.13 (age) + 0.32 (height) - 13.07 in males and -0.075 (age) + 0.18 (height) + 0.20 in females). On the other hand, height had a positive effect on DLCOSB but a negative one on DLCOSB/VA (P<0.01). We found that the predictive values from the most cited studies using predominantly Caucasian samples were significantly different from the actually measured values (P<0.05). Furthermore, oxygen uptake at maximal exercise (VO2max) correlated highly to DLCOSB (R = 0.71, P<0.001); this variable, however, did not maintain an independent role to explain the VO2max variability in the multiple regression analysis (P>0.05). Our results therefore provide an original frame of reference for either DLCOSB or DLCOSB/VA in Brazilian males and females aged 20 to 80 years, obtained from the standardized single-breath technique.

Evaluation of radioinduced damage and repair capacity in blood lymphocytes of breast cancer patients

Genetic damage caused by ionizing radiation and repair capacity of blood lymphocytes from 3 breast cancer patients and 3 healthy donors were investigated using the comet assay. The comets were analyzed by two parameters: comet tail length and visual classification. Blood samples from the donors were irradiated in vitro with a 60Co source at a dose rate of 0.722 Gy/min, with a dose range of 0.2 to 4.0 Gy and analyzed immediately after the procedure and 3 and 24 h later. The basal level of damage and the radioinduced damage were higher in lymphocytes from breast cancer patients than in lymphocytes from healthy donors. The radioinduced damage showed that the two groups had a similar response when analyzed immediately after the irradiations. Therefore, while the healthy donors presented a considerable reduction of damage after 3 h, the patients had a higher residual damage even 24 h after exposure. The repair capacity of blood lymphocytes from the patients was slower than that of lymphocytes from healthy donors. The possible influence of age, disease stage and mutations in the BRCA1 and BRCA2 genes are discussed. Both parameters adopted proved to be sensitive and reproducible: the dose-response curves for DNA migration can be used not only for the analysis of cellular response but also for monitoring therapeutic interventions. Lymphocytes from the breast cancer patients presented an initial radiosensitivity similar to that of healthy subjects but a deficient repair mechanism made them more vulnerable to the genotoxic action of ionizing radiation. However, since lymphocytes from only 3 patients and 3 normal subjects were analyzed in the present paper, additional donors will be necessary for a more accurate evaluation.

Effect of the aerobic capacity on the validity of the anaerobic threshold for determination of the maximal lactate steady state in cycling

The maximal lactate steady state (MLSS) is the highest blood lactate concentration that can be identified as maintaining a steady state during a prolonged submaximal constant workload. The objective of the present study was to analyze the influence of the aerobic capacity on the validity of anaerobic threshold (AT) to estimate the exercise intensity at MLSS (MLSS intensity) during cycling. Ten untrained males (UC) and 9 male endurance cyclists (EC) matched for age, weight and height performed one incremental maximal load test to determine AT and two to four 30-min constant submaximal load tests on a mechanically braked cycle ergometer to determine MLSS and MLSS intensity. AT was determined as the intensity corresponding to 3.5 mM blood lactate. MLSS intensity was defined as the highest workload at which blood lactate concentration did not increase by more than 1 mM between minutes 10 and 30 of the constant workload. MLSS intensity (EC = 282.1 ± 23.8 W; UC = 180.2 ± 24.5 W) and AT (EC = 274.8 ± 24.9 W; UC = 187.2 ± 28.0 W) were significantly higher in trained group. However, there was no significant difference in MLSS between EC (5.0 ± 1.2 mM) and UC (4.9 ± 1.7 mM). The MLSS intensity and AT were not different and significantly correlated in both groups (EC: r = 0.77; UC: r = 0.81). We conclude that MLSS and the validity of AT to estimate MLSS intensity during cycling, analyzed in a cross-sectional design (trained x sedentary), do not depend on the aerobic capacity.

Muscular function and functional mobility of faller and non-faller elderly women with osteoarthritis of the knee

Falls are a major concern in the elderly population with chronic joint disease. To compare muscular function and functional mobility among older women with knee osteoarthritis with and without a history of falls, 15 elderly women with a history of falls (74.20 ± 4.46 years) and 15 without a history of falls (71.73 ± 4.73 years) were studied. Muscular function, at the angular speed of 60, 120, and 180º/s, was evaluated using the Biodex Isokinetic Dynamometer. The sit-to-stand task was performed using the Balance Master System and the Timed Up and Go test was used to determine functional mobility. After collection of these data, the history of falls was investigated. A statistically significant difference was detected in the time taken to transfer the center of gravity during the sit-to-stand test (means ± SD; non-fallers: 0.35 ± 0.16 s; fallers: 0.55 ± 0.32 s; P = 0.049, Student t-test) and in the Timed Up and Go test (medians; non-fallers: 10.08 s; fallers: 11.59 s; P = 0.038, Mann-Whitney U-test). The results indicated that elderly osteoarthritic women with a history of falls presented altered functional mobility and needed more time to transfer the center of gravity in the sit-to-stand test. It is important to implement strategies to guarantee a better functional performance of elderly patients to reduce fall risks.

Breathing pattern, thoracoabdominal motion and muscular activity during three breathing exercises

The objective of the present study was to evaluate breathing pattern, thoracoabdominal motion and muscular activity during three breathing exercises: diaphragmatic breathing (DB), flow-oriented (Triflo II) incentive spirometry and volume-oriented (Voldyne) incentive spirometry. Seventeen healthy subjects (12 females, 5 males) aged 23 ± 5 years (mean ± SD) were studied. Calibrated respiratory inductive plethysmography was used to measure the following variables during rest (baseline) and breathing exercises: tidal volume (Vt), respiratory frequency (f), rib cage contribution to Vt (RC/Vt), inspiratory duty cycle (Ti/Ttot), and phase angle (PhAng). Sternocleidomastoid muscle activity was assessed by surface electromyography. Statistical analysis was performed by ANOVA and Tukey or Friedman and Wilcoxon tests, with the level of significance set at P < 0.05. Comparisons between baseline and breathing exercise periods showed a significant increase of Vt and PhAng during all exercises, a significant decrease of f during DB and Voldyne, a significant increase of Ti/Ttot during Voldyne, and no significant difference in RC/Vt. Comparisons among exercises revealed higher f and sternocleidomastoid activity during Triflo II (P < 0.05) with respect to DB and Voldyne, without a significant difference in Vt, Ti/Ttot, PhAng, or RC/Vt. Exercises changed the breathing pattern and increased PhAng, a variable of thoracoabdominal asynchrony, compared to baseline. The only difference between DB and Voldyne was a significant increase of Ti/Ttot compared to baseline. Triflo II was associated with higher f values and electromyographic activity of the sternocleidomastoid. In conclusion, DB and Voldyne showed similar results while Triflo II showed disadvantages compared to the other breathing exercises.

The oral motor capacity and feeding performance of preterm newborns at the time of transition to oral feeding

The objective of the present study was to determine the oral motor capacity and the feeding performance of preterm newborn infants when they were permitted to start oral feeding. This was an observational and prospective study conducted on 43 preterm newborns admitted to the Neonatal Intensive Care Unit of UFSM, RS, Brazil. Exclusion criteria were the presence of head and neck malformations, genetic disease, neonatal asphyxia, intracranial hemorrhage, and kernicterus. When the infants were permitted to start oral feeding, non-nutritive sucking was evaluated by a speech therapist regarding force (strong vs weak), rhythm (rapid vs slow), presence of adaptive oral reflexes (searching, sucking and swallowing) and coordination between sucking, swallowing and respiration. Feeding performance was evaluated on the basis of competence (defined by rate of milk intake, mL/min) and overall transfer (percent ingested volume/total volume ordered). The speech therapist's evaluation showed that 33% of the newborns presented weak sucking, 23% slow rhythm, 30% absence of at least one adaptive oral reflex, and 14% with no coordination between sucking, swallowing and respiration. Mean feeding competence was greater in infants with strong sucking fast rhythm. The presence of sucking-swallowing-respiration coordination decreased the days for an overall transfer of 100%. Evaluation by a speech therapist proved to be a useful tool for the safe indication of the beginning of oral feeding for premature infants.

Muscle strength but not functional capacity is associated with plasma interleukin-6 levels of community-dwelling elderly women

The association of plasma interleukin-6 (IL-6) levels, muscle strength and functional capacity was investigated in a cross-sectional study of community-dwelling elderly women from Belo Horizonte, Brazil. Elderly people who present controlled chronic diseases with no negative impact on physical, psychosocial and mental functionality are considered to be community-dwelling. Psychological and social stress due to unsuccessfully aging can represent a risk for immune system disfunctions. IL-6 levels, isokinetic muscle strength of knee flexion/extension, and functional tests to determine time required to rise from a chair and gait velocity were measured in 57 participants (71.21 ± 7.38 years). Serum levels of IL-6 were measured in duplicate and were performed within one single assay (mouse monoclonal antibody against IL-6; High-Sensitivity, Quantikine®, R & D Systems, USA; intra-assay coefficient of variance = 6.9-7.4%; interassay coefficient of variance = 9.6-6.5%; sensitivity = 0.016-0.110 pg/mL; mean = 0.039 pg/mL). Muscle strength was assessed with the isokinetic dynamometer Biodex System 3 Pro®. After the Shapiro-Wilk normality test was applied, correlations were investigated using Spearman and Kruskal-Wallis tests. Post hoc analysis was performed using the Dunn test. A significant negative correlation was observed between plasma IL-6 levels (1.95 ± 1.77 pg/mL) and muscle strength for knee flexion (70.70 ± 21.14%; r = -0.265; P = 0.047) and extension (271.84 ± 67.85%; r = -0.315; P = 0.017). No significant correlation was observed between IL-6 levels and the functional tests (time to rise from a chair = 14.65 ± 2.82 s and gait velocity = 0.95 ± 0.14 m/s). These results suggest that IL-6 is associated with reduced muscle strength.

Synaptic vesicle pool size, release probability and synaptic depression are sensitive to Ca2+ buffering capacity in the developing rat calyx of Held

The calyx of Held, a specialized synaptic terminal in the medial nucleus of the trapezoid body, undergoes a series of changes during postnatal development that prepares this synapse for reliable high frequency firing. These changes reduce short-term synaptic depression during tetanic stimulation and thereby prevent action potential failures during a stimulus train. We measured presynaptic membrane capacitance changes in calyces from young postnatal day 5-7 (p5-7) or older (p10-12) rat pups to examine the effect of calcium buffer capacity on vesicle pool size and the efficiency of exocytosis. Vesicle pool size was sensitive to the choice and concentration of exogenous Ca2+ buffer, and this sensitivity was much stronger in younger animals. Pool size and exocytosis efficiency in p5-7 calyces were depressed by 0.2 mM EGTA to a greater extent than with 0.05 mM BAPTA, even though BAPTA is a 100-fold faster Ca2+ buffer. However, this was not the case for p10-12 calyces. With 5 mM EGTA, exocytosis efficiency was reduced to a much larger extent in young calyces compared to older calyces. Depression of exocytosis using pairs of 10-ms depolarizations was reduced by 0.2 mM EGTA compared to 0.05 mM BAPTA to a similar extent in both age groups. These results indicate a developmentally regulated heterogeneity in the sensitivity of different vesicle pools to Ca2+ buffer capacity. We propose that, during development, a population of vesicles that are tightly coupled to Ca2+ channels expands at the expense of vesicles more distant from Ca2+ channels.

Liver lipid peroxidation and antioxidant capacity in cerulein-induced acute pancreatitis

The aim of this study was to evaluate the role of oxidative damage in pancreatitis-induced hepatic injury. Thirty-five rats were divided into five groups (each of 7 rats): control, cerulein (100 µg/kg body weight), cerulein and pentoxifylline (12 mg/kg body weight), cerulein plus L-NAME (10 mg/kg body weight) and cerulein plus L-arginine (160 mg/kg body weight). The degree of hepatic cell degeneration differed significantly between groups. Mean malondialdehyde levels were 7.00 ± 2.29, 20.89 ± 10.13, 11.52 ± 4.60, 18.69 ± 8.56, and 8.58 ± 3.68 nmol/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively. Mean catalase activity was 3.20 ± 0.83, 1.09 ± 0.35, 2.05 ± 0.91, 1.70 ± 0.60, and 2.85 ± 0.47 U/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively, and mean glutathione peroxidase activity was 0.72 ± 0.25, 0.33 ± 0.09, 0.37 ± 0.04, 0.34 ± 0.07 and 0.42 ± 0.1 U/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively. Cerulein-induced liver damage was accompanied by a significant increase in tissue malondialdehyde levels (P < 0.05) and a significant decrease in catalase (P < 0.05) and GPx activities (P < 0.05). L-arginine and pentoxifylline, but not L-NAME, protected against this damage. Oxidative injury plays an important role not only in the pathogenesis of AP but also in pancreatitis-induced hepatic damage.

Effects of different general anesthetics on serum hemolysis and hepatic and muscular glycogenolysis in rats

Anesthetics can affect the structure and biological function of tissues and systems differentially. The aim of the present study was to compare three injectable anesthetics generally used in experiments with animals in terms of the degree of hemolysis and glycogenolysis occurring after profound anesthesia. Twenty-four male Wistar rats (330-440 g) were divided into three groups (N = 8): chloral hydrate (CH), ketamine + xylazine (KX), Zoletil 50® (zolazepam and tiletamine) + xylazine (ZTX). After deep anesthesia, total blood was collected. The liver and white (WG) and red gastrocnemius (RG) muscles were also immediately removed. The degree of serum hemolysis was quantified on the basis of hemoglobin concentration (g/L). Hepatic and muscular glycogen concentrations (mmol/kg wet tissue) were quantified by the phenol-sulfuric method. The CH and KX groups exhibited serum hemolysis (4.0 ± 2.2 and 1.9 ± 0.9 g/L, respectively; P < 0.05) compared to the ZTX group, which presented none. Only KX induced elevated glycogenolysis (mmol/kg wet tissue) in the liver (86.9 ± 63.2) and in WG (18.7 ± 9.0) and RG (15.2 ± 7.2; P < 0.05). The CH and ZTX groups exhibited no glycogenolysis in the liver (164.4 ± 41.1 and 176.8 ± 54.4, respectively), WG (28.8 ± 4.4, 32.0 ± 6.5, respectively) or RG (29.0 ± 4.9; 25.3 ± 8.6, respectively). Our data indicate that ZTX seems to be an appropriate general anesthetic for studies that seek to simultaneously quantify the concentration of glycogen and serum biochemical markers without interferences. ZTX is reasonably priced, found easily at veterinary markets, quickly induces deep anesthesia, and presents a low mortality rate.