Links Between Hypertension and Osteoporosis: Benidipine Ameliorates Osteoporosis in Ovariectomized Hypertensive Rats Through Promotion of Osteoblast Proliferation and Inhibition of Osteoclast Differentiation

Recent studies have demonstrated that some antihypertensive drugs reduced the risk of bone fracture. Although calcium channel blockers (CCB) are used as first-line agents, there is no evidence that they prevent osteoporosis. In this study, we investigated the effects of 2 types of CCB, benidipine (L-/T-type CCB) and amlodipine (L-type CCB), on bone metabolism. In ovariectomized SHR, administration of benidipine resulted in a significant increase in the ratio of ALP to TRAP and a decrease in the number of osteoclasts in the tibia. Moreover, bone mineral density was significantly higher in the benidipine group compared with the amlodipine group, associated with a significant decrease in urinary deoxypyridinoline. In an in vitro study, benidipine promoted ALP expression and decreased receptor activator of NF-kB (RANK) ligand expression of human osteoblasts, indicating suppression of osteoclast differentiation. These pleiotropic effects of antihypertensive drugs such as benidipine might provide additional benefits in treating hypertensive postmenopausal women.     

Alanine aminotransferase (ALT) levels in a normal population and interferon therapy in chronic hepatitis C patients with normal ALT

BACKGROUND/AIMS: The aims of this study were to determine the distribution of serum alanine aminotransferase levels in a normal population and to clarify whether interferon treatment is justified in HCV-infected patients with persistently normal alanine aminotransferase levels. METHODOLOGY: The distribution of alanine aminotransferase levels was examined among 949 normal subjects who were negative for hepatitis viruses, denied regular alcohol use. Nineteen patients with chronic hepatitis C and persistently normal alanine aminotransferase levels were treated with alpha interferon (six or ten million units thrice weekly for six months). RESULTS: Peaks of alanine aminotransferase distribution among the normal subjects were seen at 16-20 IU/L and 11-15 IU/L in males and females, respectively. Fourteen of the 19 patients who received interferon treatment had favorable factors of response to interferon (eight with low pretreatment virus load, four with HCV genotype 2 and two with both). A sustained virological response was achieved in eight (57%) of 14, and alanine aminotransferase levels decreased significantly to within the normal range after interferon treatment in six of eight. CONCLUSIONS: Patients with chronic hepatitis C and persistently normal alanine aminotransferase levels should be treated with high doses of interferon if they have favorable factors of response to interferon treatment.     

A patient with primary biliary cirrhosis associated with autoimmune hemolytic anemia

Primary biliary cirrhosis is often associated with autoimmune conditions, such as thyroid disease, sicca complex, and rheumatoid arthritis. However, an association with autoimmune hemolytic anemia has rarely been reported. We present a case of primary biliary cirrhosis associated with warm type autoimmune hemolytic anemia, and we review prior reports. Received: December 7, 1998 / Accepted: June 25, 1999     

Plasma levels of atrial natriuretic peptide in patients with liver cirrhosis and its relation to ascites and renal function

Plasma immunoreactive a-human atrial natriuretic polypeptide (Ir-α-hANP) was measured by radioimmunoassay in 21 cirrhotics and 10 normal subjects. Average of Ir-α-hANP level in cirrhotics was significantly higher than in normal subjects (125.8 ± 79.6 versus 28.7 ± 12.2 pg/ml, P< 0.001). In cirrhotics without ascites, Ir-α-hANP levels were positively correlated with creatinine clearance (Ccr) and urinary sodium excretion, suggesting that α-hANP was closely related to renal circulation and sodium homeostasis. One the contrary, in cirrhotics with ascites Ir-α-hANP levels were negatively correlated with Ccr. Urinary sodium excretion in cirrhotics with ascites and Ccr more than 50 ml/min was positively correlated with Ir-α-hANP levels. However, cirrhotics with ascites and Ccr less than 50 ml/min excreted little sodium in spite of high Ir-α-hANP levels. On the basis of the Ir-α-hANP before and after treatment of ascites, cirrhotics with ascites were subdivided into 2 groups. In group I Ir-α-hANP decreased from high values and in group II it was further elevated from slightly high values by treatment. The difference in renal function and plasma volume may account for the difference in Ir-α-hANP changes in the 2 groups. This study was presented in part in the 22nd meeting of the Japanese Association for the Study of the Liver, June 6,1986, Tokyo, Japan and in 22nd meeting of the European Association for the Study of the Liver, September 5, 1987, Torino, Italy.     

Effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy—echocardiographical follow-up

To evaluate the effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy (DCM), two groups (Group I: 18 patients, Group II: 17 patients) with DCM divided by the order at the entry were followed echocardiographically for 16.9 +/- 3.0 months in Group I and 21.4 +/- 3.9 months in Group II. Metoprolol (final dose: 60 mg/day) was administered in Group I, but not in Group II (the control), although the conventional treatment for heart failure was continued. The left ventricular end-systolic dimension and ejection fraction assessed by echocardiography improved significantly after 6 months in Group I, but not in Group II, even after 48 months, although there were no significant differences in baseline data between the two groups. The end-diastolic dimension decreased significantly after 12 months in Group I only. It was estimated, using the point count method on a left ventricular endomyocardial biopsy specimen taken at entry, that the improvement (delta EF) of the ejection fraction 12 months after metoprolol administration inversely correlated (r = -0.677, p less than 0.01) with percent fibrosis, indicating that the more myocardium remains, the more improvement is expected. These findings suggested a favorable effect of beta blockade in DCM, especially in cases with less fibrosis, showing that the endomyocardial biopsy could be of clinical use in selecting candidates for chronic beta-blocker therapy in DCM.     

Reduction of linezolid-associated thrombocytopenia by the dose adjustment based on the risk factors such as basal platelet count and body weight

The aim of the present study was to evaluate the efficacy of dose modification based on the risk factor for linezolid-induced thrombocytopenia. A multivariate logistic regression analysis performed in the observational study showed that low body weight of <55 kg (odds ratio [OR]: 33.2, 95% confidence interval [CI]: 2.16–510.1, P = 0.012) and the baseline platelet count of <200 × 10³/mm³ (OR: 24.9, 95% CI: 1.53–404.7, P = 0.024) were found to be risk factors for linezolid-induced thrombocytopenia. In the subsequent intervention study, in which daily dose of linezolid was set to 20 mg/kg in patients with either one of the risk factors or 1200 mg in those without any risk factor, the onset of thrombocytopenia was significantly prolonged in the intervention study group (P = 0.043), without reducing clinical efficacy. These findings suggest that dose adjustment of linezolid is effective in preventing thrombocytopenia without reducing its clinical efficacy in patients having risk factors.     

diagnostic ultrasonography and mammography for invasive and noninvasive breast cancer in women aged 30 to 39 years

PURPOSE: To confirm which modality, ultrasonography (US) or mammography (MMG), is useful to detect breast cancer in women aged 30 to 39 years, and to compare the sensitivity and findings of these two modalities for invasive carcinoma and ductal carcinoma in situ (DCIS) in the diagnostic setting. METHODS: We retrospectively evaluated the sensitivity and findings of these two modalities in 165 patients aged 30 to 39 years, who underwent surgery at the Cancer Institute Hospital between 2001 and 2003. US or MMG were performed after obtaining information on the other modalities previously used and physical examination. The abnormal findings of US were defined as mass lesions and focal hypoechoic areas due to breast cancer. The abnormal findings of MMG were defined as category 3 to 5 (Japanese Mammography Guidelines) masses, calcifications, and other findings due to cancer. RESULTS: Of 165 patients, 147 patients (89%) mammographically showed dense breasts. Histologically, 146 (88%) were invasive carcinomas and 19 (12%) were DCIS. In all carcinomas, the sensitivity of US (95%) was higher than that of MMG (85%). The sensitivity of US for invasive carcinoma (99%) was higher than that of MMG (85%). On the other hand, the sensitivity of MMG for DCIS (89%) was much higher than that of US (68%). CONCLUSIONS: US is more sensitive to detect breast cancers than MMG in this age range, especially for invasive carcinoma. On the other hand, MMG is useful for detecting DCIS, especially when it manifests with microcalcifications.     

NLRP3 Inflammasome Inhibitor OLT1177 Suppresses Onset of Inflammation in Mice with Dextran Sulfate Sodium-Induced Colitis

Digestive Diseases and Sciences - NLRP3 inflammasomes have been reported to have a key role in the initiation and perpetuation of inflammatory bowel diseases (IBD). Here we investigated the effects...     

Preparation of Collagen/Hydroxyapatite Composites Using the Alternate Immersion Method and Evaluation of the Cranial Bone-Forming Capability of Composites Complexed with Acidic Gelatin and b-FGF

Bone-substitute materials are essential in dental implantology. We prepared collagen (Col)/hydroxyapatite (Hap)/acidic gelatin (AG)/basic fibroblast growth factor (b-FGF) constructs with enhanced bone-forming capability. The Col/Hap apatite composites were prepared by immersing Col sponges alternately in calcium and phosphate ion solutions five times, for 20 and 60 min, respectively. Then, the sponges were heated to 56 °C for 48 h. Scanning electron microscopy/energy-dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction analyses showed that the Col/Hap composites contained poorly crystalline Hap precipitates on the Col matrix. Col/Hap composite granules were infiltrated by AG, freeze-dried, and immersed in b-FGF solution. The wet quaternary constructs were implanted in rat cranial bone defects for 8 weeks, followed by soft X-ray measurements and histological analysis. Animal studies have shown that the constructs moderately increase bone formation in cranial bone defects. We found that an alternate immersion time of 20 min led to the greatest bone formation (p < 0.05). Constructs placed inside defects slightly extend the preexisting bone from the defect edges and lead to the formation of small island-like bones inside the defect, followed by disappearance of the constructs. The combined use of Col, Hap, AG, and b-FGF might bring about novel bone-forming biomaterials.     

Spontaneous regression of malignant pleural mesothelioma

We describe the spontaneous regression of a malignant pleural mesothelioma with left pleural effusion, chest pain, and a high fever (38° to 39°C) in a 37-year-old man. The patient was referred to us because multiple nodules were seen on his chest radiograph after he was successfully treated with thoracocentesis and conventional antibiotic therapy for pleural effusion. Our diagnosis was malignant pleural mesothelioma, based on histologic findings in a biopsy specimen obtained during thoracoscopy. Interestingly, the tumors markedly regressed without treatment, and the patient was doing well more than 5 months after the cancer was diagnosed. The spontaneous regression of malignant pleural mesothelioma is rare, and this may represent the first case report.