Age-related endothelium-dependent vascular relaxation in rat thoracic aorta in response to colforsin

BACKGROUND: Colforsin, a novel water-soluble forskolin derivative, increases intracellular cyclic AMP by direct stimulation of adenylate cyclase and has strong positive inotropic and vasodilative effects. However, it is not known whether colforsin causes nitric oxide (NO) release and enhances endothelium-dependent vascular relaxation. METHODS: We studied NO production and relaxation on exposure to colforsin in thoracic aorta from rats aged 4, 12 and 60 weeks. RESULTS: When a low concentration of colforsin was added to a solution bathing ring segments of aorta from 12-week-old rats, relaxation was greater in the ring segments with intact endothelium than in those from which the endothelium had been removed. A high concentration of colforsin induced the same degree of relaxation of ring segments with or without endothelium, probably by a direct effect on vascular smooth muscle cells. Production of NO in response to colforsin by cultured endothelial cells from 12-week-old rat aorta was demonstrated by the electron paramagnetic resonance spin trapping method. A low concentration of colforsin relaxed aortic segments with intact endothelium from 4-week-old rats more than those from 12-week-old or 60-week-old rats. Reversal of relaxation by NG-nitro L-arginine, an NO synthesis inhibitor, was most significant in arteries from 4-week-old rats. Production of NO after exposure to colforsin was greater in aortic segments from 4-week-old rats than older rats, as detected by an NO-selective electrode. CONCLUSIONS: Colforsin induces vasodilation in part by releasing NO from the endothelium in rat thoracic aorta. In addition to a direct vasodilative effect on the vascular smooth muscle cells, an endothelium-dependent vasodilative effect is also important in younger arteries.     

Defective response to thrombopoietin and impaired expression of c-mpl mRNA of bone marrow cells in congenital amegakaryocytic thrombocytopenia

Congenital amegakaryocytic thrombocytopenia (CAMT) is an uncommon disorder in newborns and infants, characterized by isolated thrombocytopenia and megakaryocytopenia in the first year without physical anomalies. The defect of thrombopoiesis is not well understood. Recently, thrombopoietin (TPO), the ligand for the c-mpl receptor, was cloned. Accumulating evidence from in vitro and in vivo studies indicate that TPO plays a key role in the regulation of megakaryocytopoiesis. In this study we examined the effect of TPO on megakaryocyte colony formation from a patient with CAMT using a plasma-containing methylcellulose clonal culture. The in vitro results demonstrated a defective response to TPO in megakaryocyte colony formation from bone marrow mononuclear cells (MNC) of the patient, although interleukin-3 (IL-3) but not stem cell factor (SCF) induced only a small number of megakaryocyte colonies. These findings indicated that thrombocytopenia in CAMT could not be corrected by administration of TPO in vitro. Additionally, clonal cultures containing SCF, IL-3, IL-6 and erythropoietin showed decreased numbers of erythroid and myelocytic progenitors in the bone marrow of the patient. The serum TPO level measured by enzyme-linked immunosorbent assay was significantly higher than that in healthy controls. By PCR, marrow MNC from healthy children and from a patient with essential thrombocytosis expressed c-mpl mRNA, whereas no c-mpl mRNA was detected in marrow MNC from the patient with CAMT. There was no difference in the CD34 expression and c-kit mRNA between the CAMT patient and healthy children. The results of this study suggest that the pathophysiology in CAMT may be a defective response to TPO in haemopoietic cells through impaired expression of c-mpl mRNA.     

Effects of reduced muscle temperature on the oxygen uptake kinetics at the start of exercise

SHIOJIRI, T., SHIBASAKI, M., AOKI, K., KONDO, N. & KOGA, S. 1997. Effects of reduced muscle temperature on the oxygen uptake kinetics at the start of exercise. Acta Physiol Scand 159 , 327–333. Received 25 September 1995, accepted 5 November 1996. ISSN 0001–6772. Laboratory of Exercise and Sports Science, Yokohama City University; Division of Intelligence Science, Graduate School and Technology, Division of Education, Graduate School, Faculty of Human Development, Kobe University; and Applied Physiology Laboratory, Kobe Design University, Japan. The purpose of this study was to examine the effects of reduced muscle temperature (T_m ) on gas exchange kinetics and haemodynamics at the start of exercise. Six male subjects performed moderate cycle exercise under reduced (C) and normal (N) T_m conditions. T_m and rectal temperature were significantly reduced by immersion in cold water (by 6.6 °C and 1.8 °C, respectively). The increases in oxygen uptake (V˙o ₂) and oxygen pulse (V˙o ₂/HR) during phase 1 (abrupt increase after the start of exercise) were significantly lower under C than under N. The time constant for O₂ under C (36.0 ± 7.7 (SD) s) was significantly greater than under N (27.5 ± 4.4 s); however, the time constants of cardiac output under C (38.3 ± 16.6 s) and N (33.7 ± 18.5 s) were similar. These results suggest that the slower V˙o ₂ on-response under reduced T_m conditions is caused by decreased O₂ extraction in working muscle and/or by impairment of oxidative reactions by reduced muscle temperature.     

Erectile dysfunction in hemodialysis patients with diabetes mellitus: Association with age and hemoglobin A1c levels

Abstract Aim: Erectile dysfunction (ED) is common in patients with diabetes mellitus (DM) as well as those undergoing hemodialysis (HD). The purpose of this study is to investigate the frequency and severity of ED in HD patients with DM and those without DM. In addition, we examined the relationship between erectile function and several risk factors, including presence of DM and hemoglobin A1c levels in HD patients. Methods: This study involved 180 patients on HD, including 66 HD patients with DM (DM‐HD) and 114 patients without DM (non‐DM‐HD). We evaluated erectile function using an abridged five‐item version of the international index of erectile function (IIEF‐5). Logistic regression analysis was used to investigate the relationship between presence of ED and several risk factors. Results: The total score of IIEF‐5 in DM‐HD patients (9.5 ± 4.2) was significantly lower than in non‐DM‐HD patients (13.5 ± 5.7). The prevalence of severe ED was 42.4% and 18.4% in DM‐HD patients and non‐DM‐HD patients, respectively. Age, cardiovascular disease history, and DM were identified as independent risk factors for the presence of ED. Furthermore, age and elevated hemoglobin A1c levels were identified as independent risk factors for the presence of severe ED. Conclusion: DM‐HD patients are more likely to have ED, and particularly severe forms of ED, than non‐DM‐HD patients. DM and elevated hemoglobin A1c levels were associated with the presence of ED or severe ED, respectively. Aging was identified as an independent factor in both ED and severe ED.     

Spontaneous peripelvic extravasation of urine due to an inflammatory aneurysm of the abdominal aorta

A 71-year-old man presented complaining of severe left flank pain. A computed tomography scan of the abdomen disclosed a left peripelvic extravasation of urine and a 4.0-cm abdominal aortic aneurysm with a significant amount of perianeurysmal thickening and prominent left hydroureter. The patient was diagnosed as having an inflammatory aneurysm of the abdominal aorta (IAAA) with peripelvic extravasations of urine. We report the results of a patient with IAAA with ureteral obstruction successfully treated with steroid therapy and a ureteral stent.     

Plasma abnormal prothrombin (PIVKA-π): A new and reliable marker for the detection of hepatocellular carcinoma

We evaluated the clinical usefulness of a protein induced by vitamin K absence, antagonist-prothrombin (PIVKA-II), in detecting hepatocellular carcinoma (HCC) specifically in patients with liver cirrhosis, and the possible correlation between levels of PIVKA-II and pathological features of HCC. Plasma levels of PIVKA-II and alpha-fetoprotein (AFP) were measured in 628 patients with various diseases, including 253 with liver cirrhosis and 116 with HCC. PIVKA-II was detected (greater than or equal to 0.1 arbitrary unit/mL) in 54.3% of HCC and the concentration showed a positive correlation with the tumour size. As a screening test for the detection of HCC, PIVKA-II produced values comparable with those of AFP with a sensitivity, specificity and validity of 52.8, 98.8 and 51.6% respectively. Sixteen of 45 patients (37%) with HCC who had low AFP (less than 100 ng/mL) levels were positive for PIVKA-II. No apparent relationship, however, could be found between the levels of PIVKA-II and the aetiology or pathological findings of HCC. These results suggest that PIVKA-II can be a reliable marker for detecting HCC in patients with liver cirrhosis.     

A New Assessment of Esophageal Varices by Endoscopic Ultrasonography Using a 15/20-Megahertz Ultrasonic Probe

Abstract: We examined esophageal varices using the new technique of endoscopic ultrasonography (EUS) that employed a high-resolution 15/20 MHz ultrasonic probe. EUS employing the direct contact method, in which the forceps-channel probe was in direct contact with the lumen, was used in patients with esophageal varices (58 cases) and in control patients without varices (32 cases). Findings were also compared with additional EUS employing the conventional balloon method which was performed on 21 of the patients with esophageal varices. The direct contact method visualized all the varices (endoscopic Grade 1 varices; 2.0 ± 0.7 mm in diameter (mean ± SD) and 11.9 ± 3.1 cm in length, endoscopic Grade 2 or 3 varices; 5.8 ± 3.2 mm in diameter and 16.3 ± 3.0 cm in length). In the 21 patients who underwent EUS by the two different methods, varices were displayed by both methods in 9 cases (7 endoscopic Grade 2 varices, and 2 Grade 3 varices). In the other 12 cases (8 endoscopic Grade 1 varices, and 4 Grade 2 varices) varices were displayed only by the direct contact method, and not by the balloon method. The direct contact method can be regarded as a useful technique for the evaluation of esophageal varices.     

Adverse drug reactions of intravesical bacillus Calmette–Guérin instillation and risk factors of the development of adverse drug reactions in superficial cancer and carcinoma in situ of the bladder

BACKGROUND: We examined the incidence and severity of adverse drug reactions following intravesical bacillus Calmette-Guerin (BCG) instillation for superficial bladder cancer including carcinoma in situ. We investigated the relationship between adverse drug reactions and patient background to clarify risk factors for the development of adverse drug reactions. METHODS: A total of 123 patients who underwent intravesical BCG instillation for treatment and prophylaxis between April 1997 and June 2000 were included in this study. Adverse drug reactions were divided into local and systemic categories and the severity of reactions was classified according to the presence or absence of postponement or discontinuation of instillation, with or without treatment for the reaction itself. RESULTS: Of 123 patients, 95.9% showed adverse drug effects and 50.4% needed some sort of treatment. Discontinuation of instillation due to adverse drug reactions was observed in nine patients. Regarding the necessity of treatment for adverse drug effects, the purpose of instillation and BCG dose were independent significant factors on multivariate analysis. CONCLUSION: Although there was a high rate of adverse drug reactions after intravesical BCG instillation, the rate of discontinuation of instillation was not high and serious adverse reactions were rare. The scale of the present study was small, but these results suggest that BCG instillation was well tolerated. When instillation is being performed for the purpose of treatment, and the BCG dose is 80 mg, greater attention might be needed to monitor for the development of adverse drug effects.