The endogenous cannabinoid anandamide inhibits cromakalim-activated K+ currents in follicle-enclosed Xenopus oocytes

The effect of the endogenous cannabinoid anandamide on K(+) currents activated by the ATP-sensitive potassium (K(ATP)) channel opener cromakalim was investigated in follicle-enclosed Xenopus oocytes using the two-electrode voltage-clamp technique. Anandamide (1-90 microM) reversibly inhibited cromakalim-induced K(+) currents, with an IC(50) value of 8.1 +/- 2 microM. Inhibition was noncompetitive and independent of membrane potential. Coapplication of anandamide with the cannabinoid type 1 (CB(1)) receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR 141716A) (1 microM), the CB(2) receptor antagonist N-[(1S)endo-1,3,3-trimethyl bicyclo heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528) (1 microM), or pertussis toxin (5 microg/ml) did not alter the inhibitory effect of anandamide, suggesting that known cannabinoid receptors are not involved in anandamide inhibition of K(+) currents. Similarly, neither the amidohydrolase inhibitor phenylmethylsulfonyl fluoride (0.2 mM) nor the cyclooxygenase inhibitor indomethacin (5 microM) affected anandamide inhibition of K(+) currents, suggesting that the effects of anandamide are not mediated by its metabolic products. In radioligand binding studies, anandamide inhibited the specific binding of the K(ATP) ligand [(3)H]glibenclamide in the oocyte microsomal fractions, with an IC(50) value of 6.3 +/- 0.4 microM. Gonadotropin-induced oocyte maturation and the cromakalim-acceleration of progesterone-induced oocyte maturation were significantly inhibited in the presence of 10 microM anandamide. Collectively, these results indicate that cromakalim-activated K(+) currents in follicular cells of Xenopus oocytes are modulated by anandamide via a cannabinoid receptor-independent mechanism and that the inhibition of these channels by anandamide alters the responsiveness of oocytes to gonadotropin and progesterone.     

Congenital lobar emphysema: evaluation and long-term follow-up of thirty cases at a single center

Congenital lobar emphysema (CLE) is characterized by overdistension and air-trapping in the affected lobe, and is one of the causes of infantile respiratory distress. In this report, we review our 27 years of experience with 30 CLE patients. Patients' medical records were evaluated with regard to age, clinical presentation, diagnostic methods, associated diseases, treatment, histopathologic findings, and final clinical and laboratory findings at the end of a long-term period. The mean age of 30 patients (18 male) at diagnosis was 4.9 +/- 6.7 months (range, 2 days-2.5 years). Tachypnea, dyspnea, cough, cyanosis, wheezing, hoarseness, and decreased breath sounds on the affected side were the main symptoms and clinical findings. On chest X-rays, emphysema was seen in all patients; shift/herniation to the opposite lung, atelectasis, and pneumothorax were observed in 16, 5, and 2 cases, respectively. Computerized tomography of the thorax was performed in 16 cases and revealed emphysema at affected lobe/lobes in all, a shift/herniation to the opposite side in 12 cases, and atelectasis of neighbor lobe/lobes in 7 cases. All 8 patients who had perfusion scintigraphy showed reduced perfusion in the affected lobe. Narrowed and flaccid bronchi were detected in one patient by using flexible bronchoscopy. Blood gas analysis was performed in 11 patients, and hypoxia and hypercarbia were revealed in 9 and 7 of these patients, respectively. The most common affected lobe was the left upper lobe (57%), followed by the right upper lobe (30%) and right middle lobe (27%). Two lobes were involved in 4 patients. Associated abnormalities were observed in 5 patients. Twenty-one patients underwent lobectomy; 9 were followed conservatively. Ages at diagnosis were significantly younger in surgically treated patients. Emphysema was detected in all pathological specimens, with an additional bronchial cartilage deficiency in 2 patients. In the surgically treated group, 2 patients died and 2 patients were lost to follow-up. In the conservatively treated group, one patient was lost to follow-up. Mean follow-up duration of all patients was 63.2 +/- 56.2 months (range, 1-209 months). At follow-up visits, all patients were doing well. In surgically treated patients, chest X-rays were normal (9 cases), or showed hyperlucency on the operated side (6 cases) or chronic changes in the operation area (2 cases). Hyperexpansion in the affected lobe was found to be reduced in all cases in the conservatively treated group.     

Decreased osteocalcin levels in patients with chronic obstructive pulmonary disease using long-term inhaled beclomethasone dipropionate.

Inhaled corticosteroids have been used in the treatment of chronic obstructive pulmonary disease (COPD) for many years. However the adverse effects of corticosteroids on bone formation may require special consideration in these patients. This study was undertaken to investigate the effects of long-term inhaled beclomethasone dipropionate treatment on the biochemical markers of bone formation. For this purpose, serum osteocalcin, alkaline phosphatase, free calcium, and inorganic phosphate levels were measured in 65 male COPD patients. Patients in the control group (n = 30) had not taken oral or inhaled corticosteroids for at least 1 year. Only those patients using beclomethasone with metered-dose inhalers were included in the treatment group (n = 35). The mean age of the control group was 61.63 +/- 1.84 (mean +/- SEM). In the treatment group, the mean age was 59.10 +/- 2.29 and patients in this group had taken beclomethasone for an average time of 23.94 +/- 2.72 months (for at least 12 months) at an average concentration of 1,142.0 +/- 79.64 microg/d. The mean serum osteocalcin levels in the control group and treatment group were 7.03 +/- 0.19 ng/mL and 3.74 +/- 0.12 ng/mL, respectively. Comparison of values between groups indicates that serum osteocalcin levels in patients using beclomethasone were significantly lower than that of patients in the control group. Serum alkaline phosphatase levels were 167.96 +/- 1.49 U/L and 168.17 +/- 1.60 U/L for the control and treatment groups, respectively. There was no statistically significant difference among these values (Student's t test; P >.05). The mean values of total serum calcium and inorganic phosphate were not statistically different between the groups (P >.05). These results indicate that long-term inhaled beclomethasone treatment in COPD patients may induce significant changes in osteocalcin levels and require close monitoring for osteoporotic changes.     

Idiopathic chronic eosinophilic pneumonia: a case report

Idiopathic chronic eosinophilic pneumonia (ICEP) is a rare cause of chronic lung disease in children and adolescents. We described four-years old boy presenting with recurrent pneumonia and symptoms of bronchial asthma. Because of peripheral eosinophilia and bilateral pulmonary infiltrates patient investigated comprehensive and chronic eosinophilic pneumonia determined histopathologically. Other conditions causing eosinophilic pneumonia were ruled out. He showed a dramatic response to oral corticosteroid therapy. This report emphasizes that ICEP should be considered in pediatric age group on a cause for chronic hypoxemi or intractable symptoms of respiratory system.     

Failure to express the P-selectin gene or P-selectin blockade confers early pulmonary protection after lung ischemia or transplantation

Endothelial P-selectin expression contributes to the first wave of neutrophil (polymorphonuclear leukocyte; PMN) influx in several inflammatory conditions. Although remote tissue ischemia, such as a crush injury to the hindlimb, may result in P-selectin-mediated pulmonary leukosequestration, it is not known whether the lungs exhibit a similar response after hypothermic preservation or when subjected to a direct ischemic insult. To determine if P-selectin may mediate early primary graft failure, left lungs harvested from male Lewis rats were preserved for 6 hr at 4°C and transplanted orthotopically into isogeneic recipients. Recipients immunodepleted of PMNs before transplantation demonstrated improved graft function; pulmonary vascular resistance was reduced ≈6-fold, arterial oxygenation was increased ≈3-fold, and recipient survival was increased ≈4-fold (P < 0.05, 0.05, and 0.005, respectively). Administration of a blocking anti-P-selectin IgG 10 min before reperfusion diminished graft PMN infiltration and resulted in improved graft function and recipient survival compared with controls. To establish the role of P-selectin in normothermic pulmonary ischemia, mice were subjected to temporary left pulmonary artery ligation. After functional removal of the nonischemic right lung, mice deletionally mutant for the P-selectin gene (P-selectin −/−) exhibited reduced PMN infiltration (≈2-fold), improved arterial oxygenation (≈2-fold), and improved survival (≈3-fold) compared with P-selectin +/+ control mice (P < 0.05, 0.01, and 0.05, respectively). These studies isolate and identify the central role of a single gene product (P-selectin) in early PMN recruitment and tissue injury after frank pulmonary ischemia and in the setting of lung transplantation after hypothermic preservation.     

Comparison of human amniotic membrane and hyaluronate/carboxymethylcellulose membrane for prevention of adhesion formation in rats

Objectives To investigate the effectiveness of human amniotic membrane (HAM) in the prevention of postoperative adhesion formation and to compare it with the efficacy of hyaluronate/carboxymethylcellulose (HA/CMC) membrane in a rat model. Methods Following pilot studies and computer-generated randomization, 23 female Wistar albino rats were operated on in the full study. One of the uterine horns with standard lesions was treated with either HAM (n = 13) or HA/CMC (n = 10) and the other uterine horn served as the control. Second look laparotomies were performed 2 weeks after the operations. Main outcome measures were extent, severity, degree, total adhesion scores and histopathologic characteristics of adhesions. Results Uterine horns treated with HAM had significantly lower total adhesion scores than the controls (5.15 ± 2.67 vs. 7.92 ± 1.50, P < 0.05). Total adhesion scores of uterine horns treated with HA/CMC membrane were significantly lower than those of the controls (4.30 ± 1.95 vs. 7.50 ± 1.84, P < 0.01). There were no significant differences between the HAM and HA/CMC groups regarding any adhesion scores. Conclusions HAM and HA/CMC membrane are both effective for prevention of adhesion formation in a rat uterine horn model; however, one does not seem to be more effective than the other.