Central angiotensinergic mechanisms in female spontaneously hypertensive rats treated with estradiol.

Estrogens reduce 0.3 M NaCl intake and palatability in a widely used model of essential hypertension, the spontaneously hypertensive rats (SHRs). Here we investigated whether the inhibitory effects of ß-estradiol (E2, 10 µg/kg b.w. subcutaneously for 8 days) on water deprived partially-rehydrated (WD-PR) ovariectomized (OVX) adult female SHRs (fSHRs, n = 4-10/group) are related to interferences on brain angiotensin II AT1 receptors (AT1r). After WD-PR, E2 reduced 0.3 M NaCl intake (1.3 ± 0.6, vs. vehicle: 3.5 ± 1.2 ml/30 min), the number of hedonic responses to intraoral NaCl infusion (57 ± 11, vs. vehicle: 176 ± 32/min), and the relative angiotensin AT1r (Agtr1a) mRNA expression in the hypothalamus. Losartan (AT1r antagonist, 100 µg) intracerebroventricularly in OVX fSHRs treated with vehicle subcutaneously abolished 0.3 M NaCl intake (0.1 ± 0.1 ml/30 min) and only transiently reduced hedonic responses to intraoral NaCl. Losartan combined with E2 decreased the number of hedonic and increased the number of aversive responses to intraoral NaCl and abolished 0.3 M NaCl intake. E2 also reduced the pressor and dipsogenic responses to intracerebroventricular angiotensin II. The results suggest that AT1r activation increases palatability and induces NaCl intake in WD-PR fSHRs. E2 reduced hypothalamic Agtr1a mRNA expression, which may account for the effects of E2 on NaCl intake and palatability and intracerebroventricular angiotensin II-induced pressor and dipsogenic responses in OVX fSHRs. Future studies considering natural fluctuations in estrogen secretion might help to determine the degree of such interference in brain neuronal activity.

Sodium palatability in male spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHRs) ingest more NaCl than normotensive strains. Here we investigated NaCl intake and taste reactivity in adult male SHRs and normotensive Holtzman rats treated or not with AT1 receptor antagonist centrally in euhydrated condition and after fluid depletion. Taste reactivity was measured by the number of orofacial expressions to intra-oral infusions of 0.3 M NaCl. In euhydrated condition, intra-oral infusions of 0.3 M NaCl produced greater number of hedonic responses in SHRs than in normotensive rats, without differences in the number of aversive responses. Compared to euhydrated condition, the treatment with the diuretic furosemide + low dose of captopril (angiotensin converting enzyme blocker) increased the number of hedonic and reduced the number of aversive responses to intra-oral NaCl in normotensive rats, without changing the number of hedonic or aversive responses in SHRs. Losartan (AT1 receptor antagonist, 100 ng/1 µl) injected intracerebroventricularly in SHRs abolished 0.3 M NaCl intake induced by water deprivation + partial rehydration, whereas only transiently (first 30 min of the 60 min test) reduced hedonic responses, without changes in aversive responses to intra-oral NaCl. Losartan intracerebroventricularly also only transiently (first 30 min) reduced the number of hedonic responses to intra-oral NaCl in euhydrated SHRs. The results suggest that NaCl palatability is increased and independent from body fluid balance in SHRs. The results also suggest that central AT1 receptors are part of the mechanisms activated to increase NaCl intake and palatability in SHRs. A partial dissociation between NaCl intake and palatability in SHRs is also suggested.

Interference with the renin-angiotensin system reduces the palatability of 0.3 M NaCl in sodium-deplete rats.

The renin-angiotensin system (RAS) controls hypertonic NaCl intake driven by sodium appetite. Here we investigated whether the antagonism of RAS interferes with hedonic and aversive orofacial motor responses, or palatability, to intraoral infusion of 0.3 M NaCl (hNaCl). Adult rats were depleted of sodium by combined sc injection of furosemide and 24 h removal of ambient sodium. In experiment 1, losartan (AT1 angiotensin II receptor antagonist, intracerebroventricular, 200 µg/µl), produced a three-fold increase in aversive orofacial motor responses to hNaCl. Losartan also suppressed hNaCl intake recorded immediately thereafter. In experiment 2, each animal had repeated recordings of hNaCl intake and orofacial responses to hNaCl distributed for 180 min. Paired recordings of intake and orofacial responses occurred within five successive blocks after the recordings of only orofacial responses when the animals were still sodium deplete (block zero). Captopril (angiotensin converting enzyme blocker, intraperitoneal, 30 mg/kg) inhibited by 75% the hedonic orofacial responses to hNaCl in blocks zero and 1. The hedonic responses to captopril remained the same throughout blocks, but became similar to vehicle from blocks 2 to 5. There was no difference in aversive responses to 0.3 M NaCl between captopril and vehicle. Captopril produced a 70-100% inhibition of hNaCl intake in blocks 1 to 5. The results suggest that angiotensin II acts in the brain increasing the palatability of hypertonic sodium during the consummatory phase of sodium appetite.

Estradiol modulates the palatability of 0.3 M NaCl in female rats during sodium appetite.

Excessive salt intake has been associated with the development or worsening of chronic diseases such as hypertension and spontaneously hypertensive rats (SHR) have a typical increased sodium preference. Estrogens reduce sodium appetite, but we do not know whether such effect relates to alterations in sodium palatability. Here we evaluated the influence of ovarian hormones on orofacial motor responses, an index of palatability, to intra-oral infusion of 0.3 M NaCl (IONaCl). Adult female SHR and normotensive Holtzman rats (HTZ) were used. Sodium appetite was produced by water deprivation followed immediately by partial rehydration by drinking water to satiation (WD-PR protocol). Immediately at the end of WD-PR, animals received an IO-NaCl for videotape recording of orofacial motor responses. At the end of IO-NaCl, they had access to two bottles containing 0.3 M NaCl and water to ingest (sodium appetite test). Bilateral ovariectomy (OVX) enhanced 0.3 M NaCl intake during the sodium appetite test and increased the frequency of orofacial hedonic responses to IO-NaCl in both strains. It had no effect on aversive responses. Estradiol treatment in SHR-OVX decreased hedonic responses and increased aversive responses to IO-NaCl. It also reduced 0.3 M NaCl intake during the sodium appetite test, but had no effect on baseline mean arterial pressure and heart rate. The results suggest that ovarian hormones restrain WD-PR-induced sodium appetite by reducing the hedonic properties of sodium taste. The results also suggest that estrogens mediate such reduction, particularly in SHR.

Blockade of ERK1/2 activation with U0126 or PEP7 reduces sodium appetite and angiotensin II-induced pressor responses in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHRs) have increased daily or induced sodium intake compared to normotensive rats. In normotensive rats, angiotensin II (ANG II)-induced sodium intake is blocked by the inactivation of p42/44 mitogen-activated protein kinase, also known as extracellular signal-regulated protein kinase1/2 (ERK1/2). Here we investigated if inhibition of ERK1/2 pathway centrally would change sodium appetite and intracerebroventricular (icv) ANG II-induced pressor response in SHRs. SHRs (280-330 g, n = 07-14/group) with stainless steel cannulas implanted in the lateral ventricle (LV) were used. Water and 0.3 M NaCl intake was induced by the treatment with the diuretic furosemide + captopril (angiotensin converting enzyme blocker) subcutaneously or 24 h of water deprivation (WD) followed by 2 h of partial rehydration with only water (PR). The blockade of ERK1/2 activation with icv injections of U0126 (MEK1/2 inhibitor, 2 mM; 2 µl) reduced 0.3 M NaCl intake induced by furosemide + captopril (5.0 ± 1.0, vs. vehicle: 7.3 ± 0.7 mL/120 min) or WD-PR (4.6 ± 1.3, vs. vehicle: 10.3 ± 1.4 mL/120 min). PEP7 (selective inhibitor of AT1 receptor-mediated ERK1/2 activation, 2 nmol/2 µL) icv also reduced WD-PR-induced 0.3 M NaCl (2.8 ± 0.7, vs. vehicle: 6.8 ± 1.4 mL/120 min). WD-PR-induced water intake was also reduced by U0126 or PEP7. In addition, U0126 or PEP7 icv reduced the pressor response to icv ANG II. Therefore, the present results suggest that central AT1 receptor-mediated ERK1/2 activation is part of the mechanisms involved in sodium appetite and ANG II-induced pressor response in SHRs.

Exercise capacity impairment in COPD patients with comorbidities.

BACKGROUND: Comorbidities are common in COPD and have been associated with reduced health status, increased health care utilization, all-cause hospitalization, and mortality. There is a scarcity of data on the relationship between comorbidities and functional capacity. OBJECTIVE: to evaluate the impact of comorbidities on functional capacity of COPD patients. METHODS: a cross-sectional study was conducted at two teaching hospitals in Fortaleza, Brazil. The functional capacity was assessed by spirometry and the 6-min walking test (6MWT). The health status was assessed by the St. George's respiratory questionnaire (SGRQ) and the COPD assessment test (CAT). The sample was stratified as having "none", "one" and "two or three" comorbidities groups. One-way ANOVA was used to compare means of the three groups and a multiple linear regression was run to predict the impact of comorbidities on 6MWT. RESULTS: Comorbidities (hypertension, coronary disease and diabetes) were found in 54% of the studied patients. The mean age of the 79 patients was 67±8 years and 55% were male. CAT scores increased from "no comorbidity" (17.9±7.7) to "one comorbidity" (22.8±6.8) and "two or three comorbidities" groups (24.2±10.2). A post hoc test showed a significant difference in the "no comorbidity" compared to the "two or three comorbidities" groups (p=0.01). The distance walked by the patients decreased from "no comorbidity" (386.1±83.2m) to "one comorbidity" (350±98m) and "two or three comorbidities" groups (312.6±91m). A post hoc test showed significant difference in the "no comorbidity" compared to "two or three comorbidities" groups (p=0.007). Numbers of comorbidities were independently associated with the 6MWT adjusting for age, severity of COPD and CAT scores. CONCLUSION: in the studied sample, the presence of comorbidities contributed to impair exercise capacity in patients with COPD.

[Effects of environmental tobacco smoke on lower respiratory system of children under 5 years of age]. / Efeitos do fumo ambiental no trato respiratório inferior de crianças com até 5 anos de idade.

OBJECTIVE: To determine the effects of second-hand smoke in the respiratory system of children under 5 years old. METHODS: A cross sectional study of a total of 1,104 children under 5 years old. Information about respiratory symptoms and illness, family history of respiratory diseases, smoking habits of household members and housing conditions were assessed by home interviews with the children's parents. RESULTS: We studied 546 boys and 558 girls. Among 611 children exposed to second-hand smoke, 82% had respiratory problems (odds ratio = 1.64; 95% confidence interval: 1.21-2.20). Children whose parents were smokers at the time of the survey were more likely to experience wheezing than children of nonsmoking parents (odds ratio = 1.66; 95% confidence interval: 1.21-2.27), shortness of breath (odds ratio = 1.91; 95% confidence interval: 1. 36-2.67), morning and day time or night coughs (odds ratio = 1.58; 95% confidence interval: 1.09-2.28). The odds ratio for asthma, bronchitis and pneumonia was greater for children exposed to second-hand smoke (odds ratio = 1.60; 95% confidence interval: 1. 11-2.31). CONCLUSIONS: Maternal smoking, paternal smoking, family history of respiratory diseases, and housing conditions are considered risk factors for respiratory diseases in children.

Prospective assessment of the risk of postoperative pulmonary complications in patients submitted to upper abdominal surgery.

OBJECTIVE: To investigate associations between preoperative variables and postoperative pulmonary complications (PPC) in elective upper abdominal surgery. DESIGN: Prospective clinical trial. SETTING: A tertiary university hospital. PATIENTS: 408 patients were prospectively analyzed during the preoperative period and followed up postoperatively for pulmonary complications. MEASUREMENTS: Patient characteristics, with clinical and physical evaluation, related diseases, smoking habits, and duration of surgery. Preoperative pulmonary function tests (PFT) were performed on 247 patients. RESULTS: The postoperative pulmonary complication rate was 14 percent. The significant predictors in univariate analyses of postoperative pulmonary complications were: age >50, smoking habits, presence of chronic pulmonary disease or respiratory symptoms at the time of evaluation, duration of surgery >210 minutes and comorbidity (p <0.04). In a logistic regression analysis, the statistically significant predictors were: presence of chronic pulmonary disease, surgery lasting >210 and comorbidity (p <0.009). CONCLUSIONS: There were three major clinical risk factors for pulmonary complications following upper abdominal surgery: chronic pulmonary disease, comorbidity, and surgery lasting more than 210 minutes. Those patients with three risk factors were three times more likely to develop a PPC compared to patients without any of these risk factors (p <0.001). PFT is indicated when there are uncertainties regarding the patient's pulmonary status.

[Respiratory morbidity in patients with and without pulmonary obstructive syndrome after upper abdominal surgery]. / Morbidade respiratória nos pacientes com e sem síndrome pulmonar obstrutiva submetidos a cirurgia abdominal alta.

BACKGROUND: We wanted to determine the postoperative pulmonary complication after upper abdominal surgery in patients with pulmonary obstrutive syndrome. METHODS: We have studied 196 patients prospectively analyzed in preoperative period with spirometry and followed for observation of PPC. The patients were divided in four groups: COPD - those with chronic bronchitis or emphysema and VEF1/CVF< 70% (27 patients). ASMA - patients with obstruction of the airway in response to provoking stimuli (44 patients). CHRONIC BRONCHITIS-EMPHYSEMA - those with the clinical diagnoses of the respective diseases but VEF1/CVF > 70% (23 patients). NORMAL - patients without pulmonary disease and normal spirometry (102 patients). RESULTS: Postoperative pulmonary complication was recognized when the patient presented atelectasis with clinical or gasometric alterations; bronchospasm that needed bronchodilator therapy; respiratory failure; mechanical ventilation or orotracheal intubation more than 48 hours in postsurgery period; tracheobronchitis characterized by the presence of purulent sputum with normal x-ray; pneumonia. Patients with pulmonary obstruction had experienced higher rates of pulmonary complications (32% vs 6%, p<0.05). The presence of obstructive lung disease was associated with an increased number of ventilator days, but was not associated with longer intensive care unit or hospital stay. CONCLUSIONS: The incidence of postoperative pulmonary complications was strongly associated with the presence of pulmonary obstructive syndrome.

Effect of melatonin administration on subjective sleep quality in chronic obstructive pulmonary disease.

Disturbed sleep is common in chronic obstructive pulmonary disease (COPD). Conventional hypnotics worsen nocturnal hypoxemia and, in severe cases, can lead to respiratory failure. Exogenous melatonin has somnogenic properties in normal subjects and can improve sleep in several clinical conditions. This randomized, double-blind, placebo-controlled study was carried out to determine the effects of melatonin on sleep in COPD. Thirty consecutive patients with moderate to very severe COPD were initially recruited for the study. None of the participants had a history of disease exacerbation 4 weeks prior to the study, obstructive sleep apnea, mental disorders, current use of oral steroids, methylxanthines or hypnotic-sedative medication, nocturnal oxygen therapy, and shift work. Patients received 3 mg melatonin (N = 12) or placebo (N = 13), orally in a single dose, 1 h before bedtime for 21 consecutive days. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and daytime sleepiness was measured by the Epworth Sleepiness Scale. Pulmonary function and functional exercise level were assessed by spirometry and the 6-min walk test, respectively. Twenty-five patients completed the study protocol and were included in the final analysis. Melatonin treatment significantly improved global PSQI scores (P = 0.012), particularly sleep latency (P = 0.008) and sleep duration (P = 0.046). No differences in daytime sleepiness, lung function and functional exercise level were observed. We conclude that melatonin can improve sleep in COPD. Further long-term studies involving larger number of patients are needed before melatonin can be safely recommended for the management of sleep disturbances in these patients.

[Acute myeloid leukemia after treatment of Hodgkin's disease]. / Leucemia mielóide aguda após tratamento da doença de Hodgkin.

The development of acute leukemia, particularly acute myeloid leukemia, represents a serious complication in patients treated with radio and/or chemotherapy for Hodgkin's disease. It has been reported with increasing frequency in the last years. Two such cases, that occurred in 87 patients treated for Hodgkin's disease, are reported. Complete autopsy was performed in both. The patients were less than 30 years old, received combined therapy during a prolonged time (more than 12 months), with an interval superior to 44 months between the diagnosis of Hodgkin's disease and the appearance of acute myeloid leukemia. The survival time was less than 12 months. Residual Hodgkin's disease was not observed.

Effect of melatonin administration on subjective sleep quality in chronic obstructive pulmonary disease

Disturbed sleep is common in chronic obstructive pulmonary disease (COPD). Conventional hypnotics worsen nocturnal hypoxemia and, in severe cases, can lead to respiratory failure. Exogenous melatonin has somnogenic properties in normal subjects and can improve sleep in several clinical conditions. This randomized, double-blind, placebo-controlled study was carried out to determine the effects of melatonin on sleep in COPD. Thirty consecutive patients with moderate to very severe COPD were initially recruited for the study. None of the participants had a history of disease exacerbation 4 weeks prior to the study, obstructive sleep apnea, mental disorders, current use of oral steroids, methylxanthines or hypnotic-sedative medication, nocturnal oxygen therapy, and shift work. Patients received 3 mg melatonin (N = 12) or placebo (N = 13), orally in a single dose, 1 h before bedtime for 21 consecutive days. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and daytime sleepiness was measured by the Epworth Sleepiness Scale. Pulmonary function and functional exercise level were assessed by spirometry and the 6-min walk test, respectively. Twenty-five patients completed the study protocol and were included in the final analysis. Melatonin treatment significantly improved global PSQI scores (P = 0.012), particularly sleep latency (P = 0.008) and sleep duration (P = 0.046). No differences in daytime sleepiness, lung function and functional exercise level were observed. We conclude that melatonin can improve sleep in COPD. Further long-term studies involving larger number of patients are needed before melatonin can be safely recommended for the management of sleep disturbances in these patients.

Morbidade respiratória nos pacientes com e sem síndrome pulmonar obstrutiva submetidos a cirurgia abdominal alta / Respiratory morbidity in patients with and without pulmonary obstructive syndrome after upper abdominal surgery

OBJETIVO: Estudar a morbidade respiratória nos pacientes com síndrome pulmonar obstrutiva submetidos a cirurgia abdominal alta. CASUÍSTICA E MÉTODO: Durante o pré-operatório, 196 pacientes candidatos à cirurgia abdominal alta eletiva responderam a um questionário padronizado e logo em seguida realizaram espirometria. Houve acompanhamento no pós-operatório até a alta hospitalar ou óbito. Os pacientes foram divididos em quatro grupos: 27 pacientes com DPOC (diagnóstico de bronquite crônica ou enfisema e VEF1/CVF < 70 por cento), 44 pacientes com diagnóstico de asma (obstrução das vias aéreas desencadeada por estímulos provocatívos) com ou sem alteração da espirometria. Outros 23 pacientes apresentavam o complexo bronquite crônica-enfisema, (quadro clínico sugestivo de bronquite ou enfisema porém com VEF1/CVF maior que 70 por cento). O grupo de 102 pacientes apresentou normalidade do ponto de vista clínico e espirométrico. Considerou-se como CPP: atelectasia com repercussão clínica e ou gasométrica, broncoespasmo que necessitou de tratamento, insuficiência respiratória aguda, ventilação mecânica e/ou entubação orotraqueal prolongada, infecção traqueobronquica e pneumonia. RESULTADOS: A incidência de complicações foi maior no grupo de pacientes com limitação do fluxo aéreo (32 por cento) em relação aos normais(6 por cento). Ao estudarmos os quatro grupos separadamente, foi observado que os pacientes com DPOC, apesar de apresentaram maior morbidade no pós-operatório, não diferiram dos demais pneumopatas. Complicaram, respectivamente, (DPOC 37 por cento, BE 34 por cento, asma 29 por cento, normal 6 por cento). Os obstrutivos triplicaram seu tempo de permanência no ventilador (média 3,1 e 1,1; respectivamente, com p<0,05). No entanto, não houve diferença em relação ao tempo de permanência na UTI e no tempo total de dias no pós-operatório. CONCLUSÃO: Os pacientes com limitação do fluxo aéreo apresentaram maior morbidade no pós-operatório de cirurgia abdominal alta. A magnitude deste fator de risco se reflete num risco relativo quase que cinco vezes maior em relação aos pneumopatas com os pacientes normais.