Effects of 174 G/C polymorphism in the promoter region of the interleukin-6 gene on plasma IL-6 levels and muscle strength in elderly women

We investigated the effect of -174 G/C single-nucleotide polymorphism in the promoter region of the IL6 gene on plasma IL-6 levels and muscle strength, and the relationship between IL-6 levels and muscle strength in elderly women. The sample consisted of 199 elderly residents (73.0 ± 7.8 years old) from rest homes and the community in Belo Horizonte, MG, Brazil. -174 G/C polymorphism was determined by direct sequencing of the product by PCR, and plasma IL-6 concentrations were measured by ELISA. Muscle strength in the knee joint was evaluated using a Biodex System 3 Pro® isokinetic dynamometer. ANCOVA was used to determine the effect of polymorphism on IL-6 levels and muscle strength, and the Pearson correlation coefficient to assess the relationship between IL-6 levels and muscle strength. -174 G/C polymorphism was associated with the plasma IL-6 levels of elderly women (P < 0.01) since homozygotes for the G allele showed high IL-6 levels (GG 3.85 pg/mL, GC + CC 2.13 pg/mL). There was no association of polymorphism on muscle strength (P > 0.05). No association was found between IL-6 levels and knee extensor muscle (r = 0.087, P = 0.306) or flexor (r = -0.011, P = 0.894) strength. An interaction between -174 G/C polymorphism and housing conditions of the sample of elderly women was identified, with the effect of genotype on IL-6 levels being higher in the institutionalized elderly. These results support the evidence that -174 G/C polymorphism of the IL6 gene associates with individual variability of plasma IL-6 levels in elderly women.

Demographic and metabolic characteristics of individuals with progressive glucose tolerance

We evaluated changes in glucose tolerance of 17 progressors and 62 non-progressors for 9 years to improve our understanding of the pathogenesis of type 2 diabetes mellitus. Changes in anthropometric measurements and responses to an oral glucose tolerance test (OGTT) were analyzed. We identified 14 pairs of individuals, one from each group, who were initially normal glucose tolerant and were matched for gender, age, weight, and girth. We compared initial plasma glucose and insulin curves (from OGTT), insulin secretion (first and second phases) and insulin sensitivity indices (from hyperglycemic clamp assay) for both groups. In the normal glucose tolerant phase, progressors presented: 1) a higher OGTT blood glucose response with hyperglycemia in the second hour and a similar insulin response vs non-progressors; 2) a reduced first-phase insulin secretion (2.0 ± 0.3 vs 2.3 ± 0.3 pmol/L; P < 0.02) with a similar insulin sensitivity index and a lower disposition index (3.9 ± 0.2 vs 4.1 ± 0.2 µmol·kg-1·min-1 ; P < 0.05) vs non-progressors. After 9 years, both groups presented similar increases in weight and fasting blood glucose levels and progressors had an increased glycemic response at 120 min (P < 0.05) and reduced early insulin response to OGTT (progressors, 1st: 2.10 ± 0.34 vs 2nd: 1.87 ± 0.25 pmol/mmol; non-progressors, 1st: 2.15 ± 0.28 vs 2nd: 2.03 ± 0.39 pmol/mmol; P < 0.05). Theses data suggest that β-cell dysfunction might be a risk factor for type 2 diabetes mellitus.

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 percent; interassay coefficient of variance = 9.6-6.5 percent; 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 percent; r = -0.265; P = 0.047) and extension (271.84 ± 67.85 percent; 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.

Detection of genetic polymorphism among and within Echinococcus granulosus strains by heteroduplex analysis of a microsatellite from the U1 snRNA genes

Polymerase chain reaction of a pentanucleotide microsatellite in the U1 snRNA gene complex generated a multiple band pattern due to the priming of paralogous sequences. Denaturation and slow renaturation of polymerase chain reaction products allow the formation of heteroduplex DNA that can be detected by its differential mobility in polyacrylamide gel electrophoresis. Heteroduplex analysis was used to determine if the U1 snRNA microsatellite could be a useful genetic marker in Echinococcus granulosus. A U1 snRNA microsatellite fragment from E. granulosus was isolated and characterized by Southern blot and sequencing. Four E. granulosus strains were analyzed: sheep, Tasmanian sheep, cattle, and camel strains. The former two showed polymorphism and shared three of the six patterns found for sheep strain. The cattle strain displayed two patterns, and the camel strain was monomorphic. The electrophoretic profiles were used for statistical analysis in order to determine genetic distance and the relationship among strains. Heteroduplex analysis can be helpful in genotyping E. granulosus strains and is useful in detecting polymorphism within strains.

Characterization and biological properties of Pouteria torta extracts: a preliminary study

Hexane, ethanol and aqueous extracts and fractions from leaves of Pouteria torta (Mart.) Radlk (Sapotaceae), a perennial tree, widespread in the Brazilian Cerrado, were tested for cytotoxicity with the Artemia salina toxicity model. Only the aqueous crude extract and the MeCN:CHCl3 fraction of the ethanol extract presented toxicity (0.28 mg/mL and 0.27mg/mL, respectively). Lupeol acetate was isolated from the hexane extract. It is the first report of lupeol acetate from the genus Pouteria.

Insulin secretion, insulin sensitivity, and hepatic insulin extraction in first-degree relatives of type 2 diabetic patients

To identify early metabolic abnormalities in type 2 diabetes mellitus, we measured insulin secretion, sensitivity to insulin, and hepatic insulin extraction in 48 healthy normal glucose-tolerant Brazilians, first-degree relatives of type 2 diabetic patients (FH+). Each individual was matched for sex, age, weight, and body fat distribution with a person without history of type 2 diabetes (FH-). Both groups were submitted to a hyperglycemic clamp procedure (180 mg/dl). Insulin release was evaluated in its two phases. The first was calculated as the sum of plasma insulin at 2.5, 5.0, 7.5, and 10.0 min after the beginning of glucose infusion, and the second as the mean plasma insulin level in the third hour of the clamp procedure. Insulin sensitivity index (ISI) was the mean glucose infusion rate in the third hour of the clamp experiment divided by the mean plasma insulin concentration during the same period of time. Hepatic insulin extraction was determined under fasting conditions and in the third hour of the clamp procedure as the ratio between C-peptide and plasma insulin levels. FH+ individuals did not differ from FH- individuals in terms of the following parameters [median (range)]: a) first-phase insulin secretion, 174 (116-221) vs 207 (108-277) æU/ml, b) second-phase insulin secretion, 64 (41-86) vs 53 (37-83) æU/ml, and c) ISI, 14.8 (9.0-20.8) vs 16.8 (9.0-27.0) mg kg-1 min-1/æU ml-1. Hepatic insulin extraction in FH+ subjects was similar to that of FH- ones at basal conditions (median, 0.27 vs 0.27 ng/æU) and during glucose infusion (0.15 vs 0.15 ng/æU). Normal glucose-tolerant Brazilian FH+ individuals well-matched with FH- ones did not show defects of insulin secretion, insulin sensitivity, or hepatic insulin extraction as tested by hyperglycemic clamp procedures

Ventilation with high tidal volume induces inflammatory lung injury

Mechanical ventilation with high tidal volumes (V T) has been shown to induce lung injury. We examined the hypothesis that this procedure induces lung injury with inflammatory features. Anesthetized male Wistar rats were randomized into three groups: group 1 (N = 12): V T = 7 ml/kg, respiratory rate (RR) = 50 breaths/min; group 2 (N = 10): V T = 21 ml/kg, RR = 16 breaths/min; group 3 (N = 11): V T = 42 ml/kg, RR = 8 breaths/min. The animals were ventilated with fraction of inspired oxygen of 1 and positive end-expiratory pressure of 2 cmH2O. After 4 h of ventilation, group 3, compared to groups 1 and 2, had lower PaO2 [280 (range 73-458) vs 517 (range 307-596), and 547 mmHg (range 330-662), respectively, P<0.05], higher wet lung weight [3.62 ± 0.91 vs 1.69 ± 0.48 and 1.44 ± 0.20 g, respectively, P<0.05], and higher wet lung weight/dry lung weight ratio [18.14 (range 11.55-26.31) vs 7.80 (range 4.79-12.18), and 6.34 (range 5.92-7.04), respectively, P<0.05]. Total cell and neutrophil counts were higher in group 3 compared to groups 1 and 2 (P<0.05), as were baseline TNF-alpha concentrations [134 (range <10-386) vs 16 (range <10-24), and 17 pg/ml (range <10-23), respectively, P<0.05]. Serum TNF-alpha concentrations reached a higher level in group 3, but without statistical significance. These results suggest that mechanical ventilation with high V T induces lung injury with inflammatory characteristics. This ventilatory strategy can affect the release of TNF-alpha in the lungs and can reach the systemic circulation, a finding that may have relevance for the development of a systemic inflammatory response

Inverse ratio ventilation in adult respiratory distress syndrome: an experimental study in dogs regarding gasometric and hemodynamic aspects

Cardiorespiratory values were measured in 14 mongrel dogs with adult respiratory distress syndrome (ARDS), before and following the pressure controlled inverse ratio ventilation (IRV) at an inspiratory to expiratory ratio of 2:1. After the administration of oleic acid, the dogs developed metabolic acidosis, arterial hypoxemia, decreased compliance and cardiac index. There were no significant changes in any hemodynamic or arterial blood gases with the institution of inverse ratio ventilation. We concluded that the IRV with I:E of 2:1 and respiratory ratio of 12 bpm did not improve the arterial blood gases in ARDS. We speculate that to get better oxygenation in this model of mechanical ventilation we'll need increase the respiratory ratio to decrease the expiratory time and provoke the intrinsic positive end expiration pressure (PEEP).

Correlation between arterial oxygen and carbon dioxide levels and response to almitrine bismesylate in normal dogs

The objectives of this study were: 1) to test the action of small doses of almitrine bismesylate (0.004 mg/Kg body weight/min) on the arterial blood gases and on pulmonary and systemic circulation during hypoventilation under controlled mechanical ventilation; and 2) to investigate possible correlations between arterial blood. O2 and CO3 levels and the response to the drug. Twenty one dogs divided into two groups were studied under controlled ventilation in a double-blind fashion: hypoventilation + placebo (HP) (seven dogs); hypoventilation + almitrine (HA) (fourteen dogs). The results showed no significant variations of the gas ex-change and hemodynamic varibles in the HP group. In the HP group, during almitrine bismesylate infusion, despite the lack of variation in the pulmonary ventilation, the PaO2 increased from 46.1 torr to 51.7 torr, the PaCO2 decreased from 61.9 torr to 57.7 torr. There were no significant variations of hemodynamic variables in the HA group. Thus we conclude that the drug improved arterial blood gases (PaO2 increased) with small increase in alveolar ventilation (PaCO2 decreased) despite the lack of changes in pulmonary ventilation, and that the drug has action on the arterial PO2 potentiated by hypoxemia and hypercapnia

Mechanisms of hypercapnia in patients with chronic obstructive pulmonary disease (COPD)

A higher ventilatory drive evaluated by the inspiratory occlusion pressure (Poc) and a respiratory pattern characterized by smaller tidal volume (VT) and higher breathing frequency (f) was detected in patients with chronic obstructive pulmonary disease (COPD), in relation to normals. The purpose of this study was to identify the possible mechanisms involved in the development of hypercapnia in those patients, at rest and during exercise. We have studied 11 normocapnic (PaCO2 ( 45 mmHg) and 9 hypercapnic (PaCO2 > 45 mmHg) COPD patients. As expected, no difference in the ventilatory response and neural drive was detected between the two groups. However, the hypercapnic patients have higher values of serum HCO-3 and lower values of PaO2 at rest and values of the ratio dead volume to tidal volume (VD/VT) significantly higher at rest (0.67 vs. 0.55) and during exercise (0.54 vs. 0.38) in relation to normocapnic individuals. There was also a significant positive correlation at rest (r = 0.66*) and during exercise (r = 0.65*; *p < 0.05), between PaCO2 and VD/VT, identifying a decreased alveolar ventilatory efficiency, important in the development of hypercapnia in those patients. when the COPD patients were divided into two distinct groups (PaCO2 ( 40 and ( 50 mmHg), a respiratory pattern characterized by higher f and smaller VT was detected in the hypercapnic group during exercise. In conclusion, a higher VD/VT linked to alterations of the respiratory pattern (lower VT) and to inequalities of ventilation/perfusion (high V/Q areas), seems to explain the hypercapnia of our COPD patients, since the ventilatory response and neural drive were similar in normo and hypercapnic patients.

Gas exchange during differential mechanical ventilation after unilateral lung injury induced by hydrochloric acid: experimental study in dogs

In order to test gas exchange in lungs with unilateral injury, when mechanical ventilation is needed, three groups (G-I, G-II, G-III) of seven dogs each were studied. Injury was induced in the left lung by injecting 0,lN, 1.0 ml per kg of body weight of hydrochloric acid, pH = 2.00. For groups I and II a conventional volumetric artificial ventilator was used. G-I was the control group. In group II a bilateral positive end-expiratory pressure (PEEP) was introduced during the last phase (phase 3) of the experiment, and in group III, a prototype of a volume cycled ventilator, with separated bellows, was used delivering tidal volumes separately to each lung through a Carlens' tube. In G-III, PEEP was introduced only to the injured lung in the last phase of the experiment. Phase l (Fl), basal phase, was similar in the three groups; phase 2 (F2) was the period after instillation of hydrochloric acid and phase 3 was the period after a 5 cmH2O bilateral PEEP was used in G-II, and a selective PEEP to the left lung was used in G-III. In each phase of the experiment, hemodynamic and gas exchange variables were obtained. Our results allowed the following conclusions: the differential lung ventilation technique maintained the alveolar ventilation of the dogs and the differential lung ventilation with unilateral PEEP was better for gas exchange (phase 3) than the conventional ventilation with bilateral PEEP (CPPB).

Trocas gasosas durante ventilaçäo com alta frequência em jatos(VAFJ) em cäes normais / Gas exchange during high frequency jet ventilation in normal dogs

A ventilaçäo de alta freqüência em jatos (VAFJ) é uma técnica de suporte ventilatório recentemente introduzida na prática médica, tendo-se-lhe atribuído vantagens em relaçäo aos sistemas convencionais de ventilaçäo artificial (p. ex., ventilaçäo com pressäo positiva intermitente - VPPI). decidimos, entäo, testar um modelo de ventilador de alta freqüência em jatos nacional (Takaoka M 995) em comparaçäo a um sistema clássico de ventilador ciclado a pressäo (BIRD Mark 7) em 24 cäes pulmöes normais, quanto as trocas gasosas pulmonares. Utilizamos os dois sistemas de ventilaçäo artificial nos animais anestesiados e curarizados, a VPPI com volume corrente entre 10 e 20 ml.kg**-1 e freqüência ventilatória de 16 ipm e a VAFJ em freqüências 250, 450, e 650, jatos. min**-1 (reais de 197, 273, e 374 respectivamente) ajustando-se a ventilaçäo pela PaCO2. Foram analisados em cada período gasometrias arterial e venosa central em ar e O2 a 100%, hematócrito, hemoglobina, temperatura do animal, débito cardíaco (Q), diferença alvéolo-arterial de pressöes parciais de O2 (P(A-a)O2), diferença de conteúdo artério-venoso de O2 (C(a-v)O2) e curto-circuito fisiológico (Qsfis/Q). Os resultados mostraram que as trocas gasosas em VAFJ foram mantidas semelhantes a VPPI até freqüências reais de 273 (equivalentes a 450) jatos. min**-1. Em freqüências superiores ocorreu decréscimo de PaO2, aumento de PaCO2 e desenvolvimento de acidose respiratória, caracterizando-se quadro de hipoventilaçäo alveolar. Tanto a P (A - a)O2 como o Qsfis/Q näo sofreram variaçöes significativas. Assim, os autores concluem que à medida que se aumenta a freqüência no nosso sistema de VAFJ ocorre hipoventilaçäo alveolar e prejuízo das trocas gasosas pulmonares com conseqüênte hipoxemia

Propedeutica dos derrames pleurais nao tuberculosos. / Propaedeutics of non-tuberculous pleural effusions

Os autores estudaram 84 casos de derrame pleural nao tuberculoso, sendo que as etiologias mais frequentes foram: empiema, parapneumonico, metastatico e insuficiencia cardiaca. As alteracoes mais acentuadas das variaveis bioquimicas e citologicas estudadas ocorreram nos casos de empiema, com as seguintes medias: proteinas 5,2g%; glicose 13,1mg%; DHL 2.668,5mU/ml; pH6,80; PCO2 96,3mmHg; contagem de globulos brancos 63.567/ml. A contagem de globulos vermelhos foi mais alta nos casos de derrame metastatico com media de 106.123/ ml. Os autores concluem que as alteracoes acima encontradas nao sao patognomonicas das etiologias citadas e enfatizam a necessidade de se interpretar os resultados com os dados clinicos, radiologicos e com outros exames de laboratorio

Ateracoes estruturais pulmonares secundarias ao trombembolismo. Estudo experimental em caes. / Pulmonary structural changes secondary to thromboembolism. Experimental study in dogs

Foram estudadas, em caes, as modificacoes estruturais pulmonares secundarias a injecao de coagulos autologos produzidos in vitro. O estudo anatomopatologico dos pulmoes, fixados em expansao, foi precedido por arteriografia post-mortem. Os autores salientam a utilidade desta metodologia e descrevem as alteracoes radiologicas, macro e microscopicas, encontradas