Ultrastructural Analysis of an Enterolith Composed of Deoxycholic Acid

A 67-year-old Japanese man underwent enterotomy because of enterolith ileus. Component analysis by infrared spectroscopy revealed that the enterolith was composed of a high concentration of deoxycholic acid. We further analyzed and compared the ultrastructure of the enterolith and a commercially available powdered form of deoxycholic acid by means of scanning electron microscopy and energy dispersive X-ray spectroscopy. Energy dispersive X-ray spectroscopy analysis revealed that the ratios of carbon and oxygen in the enterolith were equal to those in the deoxycholic acid powder. Scanning electron microscopy analysis showed rectangular prism-shaped particles on the surface of the enterolith. This structure was similar to that of the deoxycholic acid powder. The surgically removed enterolith had a twisted and coiled appearance. Possible mechanisms underlying the formation of this unique form are discussed

Advantage of Insulin Glulisine Over Regular Insulin in Patients With Type 2 Diabetes and Severe Renal Insufficiency

ObjectivesTo compare the efficacy and safety of insulin glulisine over regular insulin in patients with type 2 diabetes and severe renal insufficiency.SubjectsOur study included 18 patients with type 2 diabetes and a mean (range) estimated glomerular filtration rate of 13.2 mL/minute/1.73 m2 (5.8-27.6), which corresponds to stage 4-5 chronic kidney disease.DesignAfter titration of doses, regular insulin was administered thrice daily on Day 1, along with continuous glucose monitoring for 24 h starting at 7 am. Exactly equal doses of insulin glulisine were administered on Day 2. Area under the curve (AUC) for blood glucose level variation after breakfast (AUC-B 0-4), lunch (AUC-L 0-6), and dinner (AUC-D 0-6) were evaluated.ResultsAUC-B 0-4 and AUC-D 0-6 were significantly lower with insulin glulisine than with regular insulin (AUC-B 0-4: 3.3 ± 4.7 vs. 6.2 ± 5.4 × 102 mmol/L·minute, respectively, P = .028; AUC-D 0-6: 1.8 ± 7.3 vs. 6.5 ± 6.2 × 102 mmol/L·minute, respectively, P = .023). In contrast, AUC-L 0-6 was higher with insulin glulisine than with regular insulin (AUC-L 0-6: 7.6 ± 6.4 vs. 4.2 ± 8.7 × 102 mmol/L·minute, respectively, P = .099), suggesting a prolonged hypoglycemic action of regular insulin after lunch.ConclusionsInsulin glulisine effectively suppressed postprandial hyperglycemia, whereas regular insulin caused a prolonged hypoglycemic action. These findings support the effectiveness and safety of insulin glulisine in patients with type 2 diabetes and severe renal insufficiency

Pathological involvement of chymase-dependent angiotensin II formation in the development of cardiovascular disease

Chymase is a potent and specific angiotensin II (Ang II)-forming enzyme in vitro. There is also strong evidence to suggest its importance in vivo. Recent clinical studies have suggested that high serum cholesterol levels are associated with increased vascular chymase activity and this may assist in the development of atherosclerosis. This clinical finding has been reproduced in hamster models. Studies with transgenic mice overexpressing the human chymase gene suggest a direct association between vascular chymase upregulation and atherogenesis. There is also increased chymase activity following various cardiac diseases such as myocardial ischaemia, volume overload cardiac failure, cardiomyopathy and viral myocarditis, suggesting that increased cardiac chymase activity appears to be involved in cardiac remodelling

Positive correlation between blood pressure or heart rate and chymase-dependent angiotensin II-forming activity in circulating mononuclear leukocytes measured by new ELISA

The aim of the present study was to establish a convenient clinically applicable assay method for chymase-dependent angiotensin II forming activity of circulating mononuclear leukocytes (CML), which was potentially a marker of tissue chymase activity. Using this method, association between CML chymase activity and clinical parameters was determined. Cardiovascular outpatients (n = 170) without taking antihypertensive medication were recruited. An ELISA for chymase-dependent angiotensin II-forming activity in CML was established using Nma /Dnp-modified angiotensin I. Logistic regression analysis revealed that age and male gender were significant independent determinants of the increased CML chymase activity. After adjustment by age and gender, the CML chymase activity was positively correlated with systolic blood pressure, pulse rate, and the brain natriuretic peptide level. The relation between blood pressure and CML chymase activity suggests that it might reflect that increased tissue chymase activity contributes to systemic high blood pressure and heart rate because plasma chymase is inactive due to inhibitory plasma inhibitors

Prospective single-arm observational study of human chymase inhibitor Polygonum hydropiper L in subjects with hypertension

Background and Purpose: Human chymase (h-chymase) is a serine protease that forms local angiotensin II and has been proven to be related to onset of hypertension, arteriosclerosis, and post myocardial infarction cardiac remodeling. Since no chymase inhibitor was clinically available, an extensive screening for inhibition of h-chymase in three different extracts (water, hot water,  and ethanol) of approximately 800 food ingredients had been performed and we identified Polygonum hydropiper L (Polygonum). Using a dried and powdered Polygonum, we conducted a prospective, single-arm, pilot study to investigate its safety and antihypertensive effect in subjects with normal high blood pressure to moderate hypertension. Methods: First, a single oral dose of Polygonum powder (4000 mg) was administered to assess acute toxicity. Then, a pilot study was conducted in 11 subjects using the sequence of placebo and Polygonum for 2 weeks each. The dose of Polygonum was increased sequentially (200–2000 mg/day). Home blood pressure and pulse rate were monitored. Results: Oral administration of Polygonum (4000 mg) did not cause any adverse events. In the dose-escalation phase, evening systolic blood pressure was significantly decreased at 800 mg, 2000 mg doses post-treatment (p < 0.05, and p < 0.05, respectively). Depressor responders to Polygonum intake had significantly higher salt intake in spot urine (p < 0.05). No adverse events or reactions occurred. Conclusion: This was the first investigation that an h-chymase inhibitory Polygonum intake for safety and tolerability was proven and, in addition, chymase inhibitory Polygonum appeared to have depressor effect especially in a hypertensive subject with excessive salt intake

Efficacy and safety of a combination antihypertensive drug (olmesartan plus azelnidipine): “Issues with hypertension studies in real-world practice”

Background: This study investigated whether a combination drug containing an angiotensin II receptor blocker (ARB) and a calcium channel blocker (CCB) could provide effective antihypertensive therapy. Methods: A multicenter, prospective, open-label study was conducted at the clinics of Clinical Research Network. The subjects had uncontrolled blood pressure (BP) despite ARB or CCB monotherapy. The effect on both office and home BP was examined after patients switched to a combination drug (REZ: containing 20 mg of olmesartan [OL] and 16 mg of azelnidipine [AZ]). Results: A total of 78 patients were enrolled. After switching to REZ, a significant and sustained reduction of office BP was observed. The proportion of patients who achieved the target for both office and home BP was an increase from 0% to 55%. Switching from amlodipine to REZ resulted in a significant and sustained decrease of office and home BP. There was also a significant decrease of home pulse rate (PR), but office PR was unchanged. To determine the accuracy of the BP and PR values reported by patients, the frequency of each number as the first digit was determined. The frequency of “0” was extremely high for both office and home BP values, and the same was noted for home PR values. Conclusion: The results of this study suggested that switching from a single drug to combination therapy with REZ could achieve a stronger antihypertensive effect. However, concern was raised regarding the methods of BP and PR measurement and recording in this clinical trial involving general practitioners

Add-on aliskiren treatment can decrease blood pressure but requires attention to risks of renal impairment and hyperkalemia Chikushi Anti-Hypertension Trial-Rasilez® (CHAT-Ras)

Background Renin is the starting point of the renin angiotensin (RA) system cycle. Aliskiren (AL), which is a direct renin inhibitor, suppressed the entire RA cycle. In the present study, the efficacy of add-on of AL treatment in patients with essential hypertension (HT) was investigated. Methods This study was a multi-center, open-label, prospective, observational study. Study subjects were patients with essential HT and poor blood pressure (BP) control, who had received calcium channel blocker monotherapy or angiotensin II receptor blocker monotherapy or had not received any BP lowering drugs. Following add-on of AL for 12 months, BP and additional laboratory findings were analyzed. Results A total of 150 subjects were enrolled. There were 50 dropout subjects including discontinuation. Dropouts were the highest in the ARB combination therapy group at 9 subjects due to adverse events, and 3 of them were due to hyperkalemia. A significantly higher number of patients with chronic kidney disease (CKD) dropped out compared to patients without CKD (φ = 0.166, p < .05). BP before add-on of AL was 155/88 mmHg. After add-on of AL, BP was significantly improved and this lowering was sustained for 3 months (136/78 mmHg, p < .001), 6 months (136/77 mmHg, p < .001) and 12 months (134/78 mmHg, p < .001). In contrast, add-on of AL increased the potassium level and decreased the estimated glomerular filtration rate. Conclusion While add-on AL treatment achieved a favorable and sustained decrease of BP in this study, caution is necessary with regard to elevation of potassium levels and renal impairment

Prospective direct comparison of antihypertensive effect and safety between high-dose amlodipine or indapamide in hypertensive patients uncontrolled by standard doses of angiotensin receptor blockers and amlodipine

Objective: When hypertension is uncontrolled by routine treatment with an angiotensin II receptor blocker (ARB) and the calcium channel blocker amlodipine (5 mg), the dose of amlodipine can be increased or a diuretic can be added. We investigated the more effective option in a prospective multicenter open-label study. Methods: Hypertensive patients were recruited if the target blood pressure (BP) in The Japanese Society of Hypertension 2009 guideline could not be achieved with standard-dose ARB therapy and amlodipine (5 mg). Patients: Patients were divided into three groups. Group-1 was switched to a combination of irbesartan (100 mg) and amlodipine (10 mg). Group‐2A was changed to a combination of irbesartan (100 mg), amlodipine (5 mg), and indapamide, while Group-2B received a standard-dose ARB and amlodipine (5 mg) plus indapamide. Patients were assigned by their attending physicians and were followed for 6 months. The primary endpoint was the antihypertensive effect of each regimen. Results: Group‐1 contained 85 patients, Group‐2A had 49 patients, and Group‐2B had 4 patients. We only analyzed Group‐1 and Group‐2A due to the small size of Group‐2B. In both groups, systolic BP and diastolic BP were significantly decreased up to 6 months (all p < 0.001). Reduction of systolic BP was greater in Group-1 than Group‐2A after 1 month and 6 months (both p < 0.05). Uric acid was increased in Group‐2A after 3 months, but not at 6 months. Conclusion: Although both regimens were effective for reducing BP, increasing amlodipine to 10 mg daily controlled hypertension without elevation of serum uric acid