RAMP2 and RAMP3 mRNA levels are increased in failing rat cardiomyocytes and associated with increased responsiveness to adrenomedullin

Adrenomedullin (AM) is a potent vasorelaxing peptide with natriuretic and diuretic actions. Recent data indicate that AM may function as an endogenous regulator of cardiac function. We investigated to what extent AM, the AM receptor subtypes, and AM receptor-associated proteins were regulated in cardiomyocytes and non-cardiomyocytes of rats with congestive heart failure (CHF), and whether such regulation was paralleled by corresponding alterations of functional responses to AM. Cardiomyocytes and non-cardiomyocytes were isolated from myocardial tissue of rats 7 days after induction of myocardial infarction or sham operation. AM immunoreactivity was found in cardiomyocytes, endothelial cells, and fibroblasts. Robust increase of AM mRNA levels was observed both in the cardiomyocytes and in the non-cardiomyocytes of CHF rats compared to that of sham-operated rats (2.7-fold and 3.7-fold, respectively, P <0.05). Fairly high mRNA levels and immunoreactivity against the AM receptor chaperone receptor activity-modifying protein-2 (RAMP2) were also detected in the cardiomyocytes and non-cardiomyocytes. However, induction of RAMP2 mRNA expression was restricted to cardiomyocytes (1.8-fold increase in cardiomyocytes from CHF rats vs. sham rats; P <0.05). In contrast, very low levels of RAMP3 mRNA were observed. RAMP3 mRNA levels, however, were elevated in both cardiomyocytes and non-cardiomyocytes from CHF rats (6.5-fold and 2.4-fold increase vs. sham rats, respectively; P <0.05). Parallel increases of specific AM receptor binding sites and of AM-stimulated adenylyl cyclase activities were observed in failing cardiomyocytes compared to cardiomyocytes from sham rats (fivefold and sixfold increase, respectively; P <0.05). Thus, this study demonstrates that AM mRNA levels, AM receptor binding sites, and AM-stimulated adenylyl cyclase activities are increased in cardiomyocytes from failing rat hearts. Furthermore, our data suggest that induction of RAMP2 and RAMP3 contributes to the increased responsiveness to AM in failing cardiomyocytes.     

Varus Femoral Osteotomy Improves Sphericity of the Femoral Head in Older Children With Severe Form of Legg-Calvé-Perthes Disease

Background  

In the Norwegian prospective study on Legg-Calvé-Perthes disease (LCPD), we found varus femoral osteotomy gave better femoral head sphericity at a mean of 5 years postoperative than physiotherapy in children older than 6.0 years at diagnosis with femoral head necrosis of more than 50%. That study did not include separate analyses for hips with 100% necrosis and those with a percentage of necrosis between 50% and 100%.     

Epidemiology of perforated peptic ulcer:Age-and gender-adjusted analysis of incidence and mortality

AIM:To investigate the epidemiological trends in inci-dence and mortality of perforated peptic ulcer(PPU)in a well-defined Norwegian population. METHODS:A retrospective,population-based,single-center,consecutive cohort study of all patients diag-nosed with benign perforated peptic ulcer.Included were both gastric and duodenal ulcer patients admitted to Stavanger University Hospital between January 2001 and December 2010.Ulcers with a malignant neoplasia diagnosis,verified by histology after biopsy or resection,were excluded.Patients were identified from the hospitals administrative electronic database using pertinent ICD-9 and ICD-10 codes(K25.1,K25.2,K25.5, K25.6,K26.1,K26.2,K26.5,K26.6).Additional searches using appropriate codes for relevant laparoscopic and open surgical procedures(e.g.,JDA 60,JDA 61,JDH 70 and JDH 71)were performed to enable a complete identification of all patients.Patient demographics,presentation patterns and clinical data were retrieved from hospital records and surgical notes.Crude and adjusted incidence and mortality rates were estimated by using national population demographics data. RESULTS:In the study period,a total of 172 patients with PPU were identified.The adjusted incidence rate for the overall 10-year period was 6.5 per 100 000 per year(95%CI:5.6-7.6)and the adjusted mortality rate for the overall 10-year period was 1.1 per 100 000 per year(95%CI:0.7-1.6).A non-significant decline in ad-justed incidence rate from 9.7 to 5.6 occurred during the decade.The standardized mortality ratio for the whole study period was 5.7(95%CI:3.9-8.2),while the total 30-d mortality was 16.3%.No difference in in-cidence or mortality was found between genders.However,for patients≥60 years,the incidence increased over 10-fold,and mortality more than 50-fold,compared to younger ages.The admission rates outside office hours were high with almost two out of three(63%) admissions seen at evening/night time shifts and/or during weekends.The observed seasonal variations in admissions were not statisti     

Elevated hepatocyte growth factor in sera from patients with insulin-dependent diabetes mellitus

Hepatocyte growth factor (HGF) is a pleiotropic cytokine known to be involved in tissue regeneration and repair. We measured serum levels of HGF in patients with insulin-dependent diabetes mellitus (type 1). The patients were divided into four groups: (1) 10 patients at clinical presentation before insulin treatment; (2) 19 patients with newly diagnosed type 1 diabetes (diabetes duration 1/2–3 years); (3) 14 patients with long-standing type 1 diabetes without renal involvement (diabetes duration >10 years, and urinary albumin excretion (UAER) <20 μg/ min); and (4) 20 patients with long-standing type 1 diabetes with renal involvement (diabetes duration >10 years and UAER 20–500 μg/min). Sera from 24 age- and sex-matched healthy blood donors constituted a control group. The HGF levels of the four groups were (mean±SD); group 1, 0.74±0.14; group 2, 0.78±0.40; group 3, 0.86±0.42; group 4, 0.79±0.27 ng/ml, compared to 0.43±0.24 ng/ml in the control group (P<0.0008). HGF levels were not significantly different between the four patient groups. The elevated serum HGF levels did not correlate with complications related to type 1 diabetes, such as UAER, retinopathy and macrovascular complications, suggesting that HGF levels were not associated with the type 1 diabetes complications. In conclusion, our results show that type 1 diabetic patients have increased serum HGF levels compared with controls and that HGF is elevated to the same extent in newly diagnosed as well as in long-standing type 1 diabetes. Received: 29 November 1997 / Accepted in revised form: 11 March 1998     

Similar mechanisms of action of defined polysaccharides and lipopolysaccharides: characterization of binding and tumor necrosis factor alpha induction.

Little has been reported about the effects of different polysaccharides on cytokine production from human monocytes. In this study, we show that several well-defined polysaccharides, including polymers with different sizes of beta 1-4-linked D-mannuronic acid (poly-M, high-M alginate, and M-blocks) and cellulose oxidized in the C-6 position, induced human monocytes to produce tumor necrosis factor alpha (TNF-alpha). Poly-M was the most efficient polysaccharide tested and, on a weight basis, was approximately as efficient as lipopolysaccharide (LPS) from Escherichia coli. TNF-alpha production was shown to depend strongly on the molecular weights of poly-M and high-M alginate, with maximal TNF-alpha production occurring at molecular weights above 50,000 and 200,000, respectively. G-blocks, alpha 1-4-linked L-guluronic acid polymers that did not induce cytokine production from monocytes, reduced the cytokine production induced by the beta 1-4-linked polyuronic acids and LPS. Furthermore, both G-blocks and LPS were found to inhibit the binding of poly-M to monocytes, as measured by flow cytometry. In addition, we found that the binding of LPS to monocytes was inhibited by G-blocks, M-blocks, and poly-M. Our results indicate that beta 1-4-linked polyuronic acids and LPS may stimulate monocytes to produce TNF-alpha by similar mechanisms and may bind to a common receptor.     

Effect of trituration on dimensional changes of dental amalgam.

The dimensional changes of dental amalgams during setting was evaluated using different methods of specimen production, and measurement procedures. Amalgam specimens were prepared from 10 commercially available dental amalgam alloys by mechanical condensation. Dimensional change was measured on microcators with a measuring load of 1 g. The variation in dimensional change with trituration was substantial, and similar to the difference between various brands of alloys at the same trituration time. Porosity seems to vary between 0.1 and 0.6% independent of severity of trituration except for two alloys in which increased trituration time seemed to reduce porosity. It was therefore pointed out that even though trituration in most cases can be altered to make an amalgam expand, such procedures should not be followed since optimal values of other clinically significant properties may not be maintained.     

Correlation between strength and hardness of dental casting gold alloys.

The yield strength, tensile strength, and hardness of Type IV dental casting gold alloys were measured. Regression lines and prediction intervals for the estimation of yield strength and tensile strength from hardness measurements were then determined. The 95% prediction intervals for the yield strength and tensile strength were found to be +/- 45 MN/m2 and +/- 105 MN/m2, respectively.     

Plate fixation of tibial fractures in the rabbit: Correlation of bone strength with duration of fixation

Bone healing after metal plate fixation of rabbit tibial osteotomies was studied in order to gain information as to the optimum time for plate removal. The fracture had regained almost normal biomechanical properties after 6 weeks. Significantly greater strength and stiffness of the healing tibiae were obtained at 12 weeks when the plate was removed after 4, 6 or 9 weeks and no further fixation was subsequently applied, compared to those plated for 12 weeks. The results indicate that a metal plate should be removed as soon as the fracture has regained normal biomechanical properties; i.e. before the stress-protecting effect has secondarily weakened the bone.

The findings suggest that metal plates should be removed at an earlier stage of the healing period than is usual in clinical practice.     

Low doses of methylphenidate (Ritalin) may alter the delay-of-reinforcement gradient

The present study investigated effects of methylphenidate on spatio-temporal distributions of responses generated by a fixed interval 60-s schedule of reinforcement. A response panel with 20 different response locations (holes) made it possible to distinguish effects of the drug on the procedurally-correct response (correct according to the contingencies) and effects on other topographically similar responses acting as functionally-adequate responses. Detailed flow charts show how the dynamics of responding changed with dose and segment of the fixed interval. The number of holes visited was increased after low and medium doses, but decreased after high doses. The spatial differences between responses in the initial and the final parts of the fixed interval gradually disappeared after 6 mg/kg or higher doses as the functionally-adequate responses moved to earlier segments of the fixed interval. Few results could, however, be described as response rate dependent. Distributions of responses around the correct hole illustrated differences between procedurally-correct and functionally-adequate classes. The number of holes included in the latter class changed by dose in an inverted U-shaped fashion. Perseverations and stereotyped responding increased with increasing dose. Most of the effects may be described as motor stimulatory. One way of explaining the stimulatory effect is in terms of a lengthened delay-of-reinforcement gradient. The rate-dependent effect of methylphenidate on the procedurally-correct class after some doses may have been due to the combined effects of a lengthened delay gradient increasing the response rates early in the interval and interference from perseverations having their most detrimental effects on the high rates late in the interval. Offprint request to: T. Sagvolden