Effect of AT2 receptor on expression of AT1 and TGF-beta receptors in VSMCs from SHR

We recently reported that overexpression of the angiotensin II type 2 (AT2) receptor downregulates the AT1a receptor through the bradykinin/NO pathway in a ligand-independent manner in vascular smooth muscle cells (VSMCs). In the present study, we investigated the effect of AT2 receptor overexpression on the expression of the AT1a receptor and transforming growth factor-beta (TGF-beta) receptor subtypes in VSMCs from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Transfection of the AT2 receptor gene downregulated expression of the AT1a receptor in VSMCs from WKY, but did not affect expression of the AT1a receptor in VSMCs from SHR. Transfection of the AT2 receptor abolished DNA synthesis in response to angiotensin II in VSMCs from WKY; in VSMCs from SHR, basal DNA synthesis was suppressed, but DNA synthesis in response to Ang II was not altered. The NO substrate L-arginine augmented downregulation of the AT1a receptor in VSMCs from WKY, whereas it did not affect expression of the AT1a receptor in VSMCs from SHR. In response to AT2 receptor transfection, expression of TGF-beta type I receptor mRNA was suppressed significantly in VSMCs from WKY, whereas expression of TGF-beta type I receptor was not altered in VSMCs from SHR. These results suggest that the AT2 receptor downregulates AT1a and TGF-beta type I receptors in normal VSMCs, but not in SHR-derived VSMCs. The lack of downregulation of the AT1a receptor may contribute, in part, to the exaggerated growth of VSMCs from SHR.     

A case of bronchial gland cell-type adenocarcinoma with relapsed pneumonia and hemoptysis]

We report a case of bronchial gland cell-type adenocarcinoma with recurrent pneumonia and hemoptysis. After persistent hemoptysis since the summer of 1999, a 26-year-old female patient was admitted to our hospital because of bacterial pneumonia of the left lower lobe in March 2000. Treatments with antibiotics resulted in only a transient improvement of the pneumonia, and so she was re-admitted for an investigation of the recurrent pneumonia accompanied with hemoptysis. Bronchofiberscopy revealed a polypoid lesion at the orifice on the left B10 bronchus. Although the microscopic examination of the biopsied specimens showed only non-specific inflammatory changes, a left lower lobectomy was performed. The pathological examination of the resected lung confirmed that the polypoid region was bronchial gland cell type adenocarcinoma at the stage of pT1N0M0.     

Association between activating mutations of calcium-sensing receptor and Bartter's syndrome

Bartter's syndrome is a heterogeneous disorder characterised by deficient renal reabsorption of sodium and chloride, and hypokalaemic metabolic alkalosis with hyper-reninaemia and hyperaldosteronaemia. Mutations in several ion transporters and channels have been associated with the pathogenesis of Bartter's syndrome. We describe two hypocalcaemic patients with deficient parathyroid hormone secretion who also showed characteristics of Bartter's syndrome. We found activating mutations of the gene for the calcium-sensing receptor (CASR) in both patients. Activation of this calcium-sensing receptor inhibits the activity of a renal outer-medullary potassium channel that is mutated in type 2 Bartter's syndrome. We therefore suggest that some activating mutations of CASR could provide new mechanisms for the development of Bartter's syndrome.     

Evidence for the expression of alcohol dehydrogenase class I gene in rat uterus and its up-regulation by progesterone

The endometrium is one of the target tissues of the ovarian steroid hormones, estrogen and progesterone. In order to elucidate the mechanism of gene regulation in the endometrium, suppressive subtraction hybridization was performed to isolate the candidate genes controlled by progesterone in rat uterus. Alcohol dehydrogenase (ADH) class I gene was one of the candidate genes. Here we investigated the expression and regulation of ADH class I gene in rat uterus. The mRNA of ADH class I was detected in uterus by RT-PCR using specific primers. Using specific probe for ADH class I, in situ hybridization was performed to investigate localization in rat uterus. Positive signals were detected in the endometrial stromal cells of rat uterus by in situ hybridization and were not detected in endometrial epithelial cells and myometrium in rat uterus. Ovariectomized rats were treated with 17-beta estradiol and progesterone and the uteri of these rats were used for Northern blot analysis and assay of the ADH activity. Northern blot analysis revealed that the expression of ADH class I mRNA in rat uteri was up-regulated approximately two-fold after progesterone treatment, but not estrogen. Likewise, ADH activity was approximately two-fold higher in progesterone-treated rat uteri compared with controls. This study demonstrated that ADH class I gene is progesterone-responsive in the uterus. This implies that progesterone might be involved with retinoic acid synthesis in the uterus, since ADH is the key enzyme for retinoic acid synthesis.     

The effect of oral appliance therapy on blood pressure in patients with obstructive sleep apnea

The objective of the study was to investigate the effects of oral appliance (OA) therapy on ambulatory blood pressure in patients with obstructive sleep apnea (OSA). Eleven OSA patients who received OA therapy were prospectively investigated. Ambulatory blood pressure was measured for 20 h from 4:00 p.m. to 12:00 noon the next day using an ambulatory blood pressure monitor. The Respiratory Disturbance Index (RDI) was measured in the pretreatment and posttitration periods. The OA was titrated to reach a therapeutic jaw position over 2 to 8 months, and posttitration measurements were repeated. At posttitration, the RDI was significantly decreased from a mean (SD) of 24.7 (20.1) to 6.1 (4.5). Significant reductions in diastolic blood pressure (DBP) and mean arterial pressure (MAP) were found for the 20-h periods, and systolic blood pressure (SBP), DBP, and MAP while asleep. The mean values were 79.5 (5.5) to 74.6 (6.0) for DBP and 95.9 (5.4) to 91.2 (5.9) for MAP, for over a 20-h period, and 118.4 (10.0) to 113.7 (9.1) for SBP, 71.6 (8.0) to 67.2 (7.9) for DBP, and 88.4 (8.0) to 83.9 (7.5) for MAP, while asleep. This study suggests that successful OSA treatment with an OA may also be beneficial to lower blood pressure in OSA patients, as previously suggested for nasal continuous positive airway pressure therapy. This study was conducted in the Division of Orthodontics, The University of British Columbia, Canada     

Replacement therapy for iron deficiency improves exercise capacity and quality of life in patients with cyanotic congenital heart disease and/or the Eisenmenger syndrome

Introduction

Iron deficiency is common in cyanotic congenital heart disease (CHD) and results in reduced exercise tolerance. Currently, iron replacement is advocated with limited evidence in cyanotic CHD. We investigated the safety and efficacy of iron replacement therapy in this population.

Methods

Twenty-five iron-deficient cyanotic CHD patients were prospectively studied between August 2008 and January 2009. Oral ferrous fumarate was titrated to a maximum dose of 200 mg thrice-daily. The CAMPHOR QoL questionnaire, 6 minute walk test (6MWT) and cardiopulmonary exercise testing were conducted at baseline and after 3 months of treatment.

Results

Mean age was 39.9 ± 10.9 years, 80% females. Fourteen had Eisenmenger syndrome, 6 complex cyanotic disease and 5 Fontan circulation. There were no adverse effects necessitating termination of treatment. After 3 months of treatment, hemoglobin (19.0 ± 2.9 g/dL to 20.4 ± 2.7 g/dL, p < 0.001), ferritin (13.3 ± 4.7 μg/L to 54.1 ± 24.2 μg/L, p < 0.001) and transferrin saturation (17.8 ± 9.6% to 34.8 ± 23.4%, p < 0.001) significantly increased. Significant improvements were also detected in the total CAMPHOR score (20.7 ± 10.9 to 16.2 ± 10.4, p = 0.001) and 6MWT distance (371.7 ± 84.7 m to 402.8.0 ± 74.9 m, p = 0.001). Peak VO₂ remained unchanged (40.7 ± 9.2% to 43.8 ± 12.4% of predicted, p = 0.15).

Conclusion

Three months of iron replacement therapy in iron-deficient cyanotic CHD patients was safe and resulted in significant improvement in exercise tolerance and quality of life. Identification of iron deficiency and appropriate replacement should be advocated in these patients.     

A case of unilocular serous cystic neoplasm mimicking mucinous cystic neoplasm

A 40's woman had a cystic lesion in the tail of the pancreas that had grown over a 1.5-year period. Endoscopic ultrasound revealed a partition structure and "cyst-in-cyst" like lesion, and a diagnosis of mucinous cystic neoplasm was made. The patient underwent distal pancreatectomy with splenectomy. Following histological examination, our final diagnosis was revised to unilocular serous cystic neoplasm since the increase in cysts was due to hemorrhage and the partition structure was in fact granulation tissue. We here discuss this rare case with reference to previous published reports.     

Clinical features of healthcare-associated pneumonia (HCAP) in a Japanese community hospital: comparisons among nursing home-acquired pneumonia (NHAP), HCAP other than NHAP, and community-acquired pneumonia

Background and objective: More than 100 000 Japanese die of pneumonia every year. The number of people residing in nursing homes is increasing with the ageing of the population. In 2005, the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) published important guidelines for the management of healthcare‐associated pneumonia (HCAP). In Japan, however, the optimum strategy for management of HCAP is still unclear. The purpose of this study was to clarify the clinical features of patients with HCAP. Methods: Patients (n = 202) who were consecutively admitted with a diagnosis of acute pneumonia between October 2007 and September 2009 were retrospectively evaluated. Using the ATS/IDSA guidelines, patients were divided into three groups: a community‐acquired pneumonia (CAP) group (n = 123), a nursing home‐acquired pneumonia (NHAP) group (n = 46) and a HCAP other than NHAP (O‐HCAP) group (n = 33). These groups were then compared with respect to laboratory data, microbiological findings and mortality. Results: Thirty‐day mortality in the NHAP group (10.9%) tended to be higher than that in the CAP group (3.3%) or the O‐HCAP group (0%). The pathogens most frequently identified were Streptococcus pneumoniae and Haemophilus influenzae in the CAP group, methicillin‐resistant Staphylococcus aureus and Klebsiella pneumoniae in the NHAP group, and S. pneumoniae and K. pneumoniae in the O‐HCAP group. Conclusions: The NHAP group was clinically different from the O‐HCAP group, based on bacteriological examination and mortality rates. In order to accurately diagnose, and formulate optimum treatment strategies for Japanese patients, the categories of HCAP, as specified in the ATS/IDSA guidelines, should not be applied directly either to patients with NHAP or those with O‐HCAP.