POTASSIUM ACCELERATES URINARY SODIUM EXCRETION DURING SALT LOADING WITHOUT STIMULATING ATRIAL NATRIURETIC POLYPEPTIDE SECRETION

1. Effects of potassium (K) supplementation (100 mEq/day) on urinary sodium (Na) excretion and on the secretion of atrial natriuretic polypeptide (ANP) during salt loading (350 mEq/day) were studied in 12 healthy salt-resistant normotensives under strictly controlled metabolic ward conditions. 2. Urinary volume and Na excretion on the first day of the high salt period (HSP) were significantly greater in the K-supplemented group (KG) than in the control group (CG). 3. There was a significant gain in bodyweight after salt loading in both groups, with a significantly greater gain in CG on the second day of HSP. Haematocrit decreased significantly during salt loading in both groups, the degree of which was significantly greater in CG. 4. Plasma norepinephrine decreased significantly during salt loading in both groups, the degree of which was significantly less in KG than in CG. A significant increase in plasma ANP was observed in CG on and after the second day of HSP, while a significant increase in plasma ANP was observed on the fifth day of HSP in KG. 5. These findings indicate that K supplementation accelerates diuresis and natriuresis, resulting in moderate suppression of volume expansion induced by salt loading and that this accelerated diuresis and natriuresis is not a result of the action of ANP.     

Physiological significance of plasma free and conjugated dopamine in healthy volunteers--with special reference to sympathetic nerve activity

In order to elucidate the physiological significance of plasma dopamine, blood pressure, pulse rate (PR), plasma concentrations of free or conjugated dopamine (free or conjugated pDA), noradrenaline (pNA) and adrenaline (pAd) were measured in 9 healthy volunteers. Blood sampling for the measurements was performed at a basal condition maintaining a supine position for 60 minutes, after twenty minutes 60 degrees head-up tilt (tilt) and an intravenous infusion of 1000 ml 0.9% saline for 2 hours. Following tilt, mean values in diastolic and mean blood pressure, PR, pNA and pAd were significantly increased, while free, conjugated and total pDA were decreased. On the other hand, saline infusion yielded significant decreases in hematocrit, pNA, free, conjugated and total pDA, but blood pressure, PR and pAd remained at the same level. Free/conjugated pDA ratio did not change during tilt or saline infusion. The basal value of free, conjugated or total pDA did not significantly correlate with blood pressure, PR, pNA or pAd, respectively. Furthermore, no significant correlations between the changes in pDAs and hemodynamic parameters, pNA or pAd by tilt or saline infusion were observed. From these results, it was suggested that plasma free or conjugated dopamine in physiological conditions may not be released from sympathetic nerve endings or adrenomedullary glands. Further investigations are needed to clarify the physiological significance of plasma dopamine in humans.     

Mechanisms underlying the enhanced elevation of IL-1beta and TNF-alpha mRNA levels following endotoxin challenge in rat alveolar macrophages cultured with low-Mg2+ medium.

We have previously shown that interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha mRNA levels in rat alveolar macrophages are increased in by endotoxin (lipopolysaccharide; LPS)- stimulation and further enhanced by culturing with low-Mg2+ medium. We have now investigated the mechanisms of underlying this enhancement by using some specific signal transduction inhibitors. The enhanced elevation of both mRNAs levels was suppressed by pretreatment with TMB-8 (which inhibits calcium release from the endoplasmic reticulum) or dexamethasone (which inhibits nuclear factor [NF]-kappaB and activator protein [AP]-1), but not with verapamil or nifedipine (which inhibits calcium channels). The enhancment of IL-1beta, but not TNF-alpha mRNA levels, was suppressed by pretreatment with W-7 (which inhibits calmodulin), whereas the enhancement of TNF-alpha mRNA levels was suppressed by pretreatment with U73122 (which inhibits phospholipase C). Curcumin (an inhibitor of AP-1), suppressed the increases in both mRNAs induced by low-Mg2+ medium alone, but had no suppressive effect on the levels of either mRNA after LPS-stimulation in low-Mg2+ medium. Pyrrolidine dithiocarbamate (an inhibitor of NF-kappaB) prevented the elevation of TNF-alpha mRNA levels induced by low-Mg2+ medium without LPS-stimulation, but had no suppressive effect on IL-1beta mRNA levels. From these results, we conclude that the enhanced elevation of IL-1beta and TNF-alpha mRNA levels seen in LPS-stimulated alveolar macrophages in low-Mg2+ medium occurs partly via the same, and partly via different, signaling pathways.     

Promoter methylation and protein expression of the E-cadherin gene in the clinicopathologic assessment of adenoid cystic carcinoma.

Adenoid cystic carcinoma, a relatively uncommon tumor of salivary glands, is characterized by a prolonged clinical course and a fatal outcome. The molecular events underlying their progression are unknown. In this study, we examined the methylation status of E-cadherin gene and its protein expression in 23 cases of adenoid cystic carcinoma and correlated the results with the clinicopathologic factors to determine its role in these tumors. We also analyzed the effect of 5-azacytidine on the re-expression in a methylated cell line of adenoid cystic carcinoma for this gene. In our study, E-cadherin immunoreactivity, although heterogeneous, showed a progressive reduction with high histological grade and in metastatic and recurrent lesions. Promoter methylation was detected in 16 of 23 cases (70%), but there was no correlation with the histological grade or patient prognosis. Microdissection of immuno-negative cells in heterogeneous tumors showed positive methlyation. In the cell line from salivary adenoid cystic carcinoma with methylated E-cadherin, 5-azacytidine restored the E-cadherin expression. Our results indicate that: (1) E-cadherin gene promoter is frequently methylated in adenoid cystic carcinoma, leading to reduced E-cadherin expression, (2) variable E-cadherin expression might result from the intratumoral heterogeneity, and (3) increased extent of methylated areas may be associated with progression and advancement of the disease.     

A case of mixed connective tissue disease successfully treated for hemophagocytic syndrome with intermittent intravenous injection of cyclophosphamide]

A 52 year-old woman noticed general fatigue, polyarthralgia, and muscle weakness of lower extremities in October 2001. In December, she felt difficulty in walking due to muscle weakness. In January 2002, she admitted another hospital because of dyspnea on exertion and edema of lower extremities. Laboratory test revealed leukocytopenia, the elevation of creatine kinase and positive anti-U1-RNP antibodies. Her chest computed tomography (CT) showed severe interstitial pneumonia. Cardiac echogram revealed that she had pericardial effusion and pulmonary hypertension. Then she was transferred to Keio University Hospital and she was diagnosed as having mixed connective tissue disease (MCTD) manifestating myositis, interstitial pneumonia, pulmonary hypertension and pericarditis. Prednisolone (PSL) 60mg daily following to methylprednisolone (mPSL) pulse therapy was begun and her symptoms were gradually improved. In middle of February, she complained of high fever over 39.0 degrees C. Bacterial culture tests were negative and laboratory data indicated pancytopenia and a high level of serum ferritin. Bone marrow aspiration revealed hemophagocytosis in bone marrow specimens and she was diagnosed as having hemophagocytic syndrome associated with MCTD. mPSL pulse therapy was not effective and intermittent cyclophosphamide pulse therapy (IV-CY) was performed resulting in improvement of the symptoms. This case suggested the effectiveness of IV-CY therapy in patients with corticosteroid-resistant HPS associated with connective tissue diseases.     

Effect of intermittent parathyroid hormone (1-34) treatment on the bone response after placement of titanium implants into the tibia of ovariectomized rats.

PURPOSE: This study investigated the effect of parathyroid hormone (1-34) [PTH(1-34)] on bone reactions after tibial placement of titanium screw implants into ovariectomized rats. MATERIALS AND METHODS: Twelve-week-old female Wistar rats were divided into 3 groups of 24. The first group (Sham group) was sham-operated; the second group (OVX group) was ovariectomized only; and the third group (PTH group) was subcutaneously administered 30 microg/kg PTH in the dorsal region 3 days per week starting the fourth week after ovariectomy until the end of the experiment. Titanium screw implants were placed in the proximal metaphysis of the tibia of all 3 groups at 168 days after surgery. The animals were killed 7, 14, 28, and 56 days after implantation. Undecalcified sections were prepared and evaluated by light microscopy. Histomorphometric measurements were obtained using a computer-based image analyzer to quantify the unit bone mass around the implant and the rate of implant-bone contact. RESULTS: When PTH administration was started 21 days after ovariectomy, the volume density of bone around implants in the PTH group was almost the same as that of the Sham group throughout the entire observation period. This finding suggests that not only can intermittent human PTH(1-34) administration prevent resorption of newly generated trabeculae around an implant but also it can aid in the recovery of bone volume lost due to ovariectomy. CONCLUSION: When dental implants are applied to jaw bone showing trabecular bone loss, it may be possible to increase bone density around an implant by intermittent human PTH(1-34) administration and thereby improve clinical results.     

A case of autoimmune pancreatitis complicated with immune thrombocytopenia]

A 80-year old man was referred to our hospital because of an elevation of serum amylase level. Diffuse enlargement of the pancreas was detected by abdominal computed tomography, and also diffuse narrowing of the main pancreatic duct was revealed using endoscopic retrograde cholangiopancreatography. The serum level of IgG was elevated to 3450mg/dl. Besides, on the 10th hospital day, petechia developed and the platelet level decreased to 1.5 x 10(4)/microl. The platelet-associated IgG, antiplatelet antibody and antinuclear antibody in serum were positive. The levels of serum complements were low. From all these findings the patient was diagnosed as autoimmune pancreatitis complicated with immune thrombocytopenia. The treatment with prednisolone was started, which was effective on each disease. The medication was suspended a year ago, and so far there is no data suggesting the recurrence of autoimmune pancreatitis or immune thrombocytopenia.     

Preoperative therapeutic embolization for massive hemoptysis from bronchial collaterals in tetralogy of Fallot--a case report successfully treated by total correction

Hemoptysis from bronchial collateral arteries in cyanotic heart diseases is a troublesome complication. We report a case of Tetralogy of Fallot presented with massive hemoptysis which was successfully treated with transcatheter therapeutic embolization prior to the radical operation. A 28-years old man was admitted to our hospital because of hemoptysis and dyspnea. On the day of admission, he had a massive hemoptysis and became asphyxic. Diagnostic cardiac catheterization performed next day revealed Tetralogy of Fallot. Bronchial arteriogram demonstrated large bronchial collateral arteries with heavy staining around the right lower lobe bronchus. Therapeutic embolization with Gelfoam was performed and the hemostasis was obtained. The radical operation was performed 4 months later. Before cardiopulmonary bypass, the right bronchial artery was ligated. He was weaned from the extracorporeal circulation under the stable circulatory condition, and respirator on the first post operative day without any complications, and he was discharged on the 57th day after the operation. We emphasize the efficacy of therapeutic embolization of the well developed bronchial collateral arteries as a pretreatment of hemoptysis in the cyanotic heart disease.