Pancreatin enhanced erosion of and macromolecule release from 2,2-bis(2-oxazoline)-linked poly(epsilon-caprolactone).

The degradation and erosion of solvent cast films and injection molded bars prepared from poly(epsilon-caprolactone) (PCL) and 2,2'-bis(2-oxazoline) linked poly(epsilon-caprolactone) (PCL-O) were evaluated in simulated gastric fluid (SGF) (pH 1.2, pepsin present) and in simulated intestinal fluid (SIF) (pH 7.5, pancreatin present). After incubation of the polymer films (10 mg) and bars (70 mg) in the medium, the resulting decrease in molecular weight (degradation) was determined by size exclusion chromatography and the weight loss of the preparations was measured. In addition, the effect of pancreatin on FITC-dextran (MW 4400) release from PCL and PCL-O microparticles, prepared by w/o/w double emulsion technique, was studied. No degradation or weight loss was observed for either PCL or PCL-O films in SGF (12 h incubation, 37 degrees C). When compared to PBS pH 7.4, pancreatin hardly enhanced the weight loss of PCL films and bars. In contrast, pancreatin enhanced substantially erosion of PCL-O films and bars. Unlike PCL preparations, the PCL-O preparations showed surface erosion in SIF. Pancreatin increased considerably FITC-dextran release from both PCL and PCL-O microparticles. In conclusion, the present results demonstrate the enzyme sensitivity of the novel PCL-O polymer. In addition, the results show that pancreatin present in intestinal fluid may substantially affect drug release from PCL based preparations.     

Incidence of schizophrenia in a nationwide cohort of patients with type 1 diabetes mellitus

CONTEXT: Patients with schizophrenia have an increased risk of type 2 diabetes mellitus. However, very few studies have dealt with the association of type 1 diabetes and schizophrenia. Preliminary evidence points to a possible inverse association. OBJECTIVE: To investigate the incidence of schizophrenia in a nationwide cohort of patients with type 1 diabetes born in 1950 through 1959 in Finland. DESIGN: A cohort study of individuals born in 1950 through 1959 with a follow-up of 1969 through 1991. SETTING: Finland. PATIENTS: All individuals born in 1950 through 1959 with type 1 diabetes were identified through nationwide registers. The incidence of schizophrenia until 1992 among the total 1950-1959 cohort and in individuals with type 1 diabetes was calculated using information from 3 health care registers. MAIN OUTCOME MEASURE: Incidence of schizophrenia. RESULTS: The incidence of schizophrenia was 0.21 per 10 000 person-years in the group with type 1 diabetes and 0.56 per 10 000 person-years in the group without type 1 diabetes (P < .001). CONCLUSION: The incidence of schizophrenia is decreased in patients with type 1 diabetes.     

Lower limb motor restlessness in Asperger's disorder, measured using actometry

The movement disturbances and brain imaging findings in Asperger's disorder (AD) suggest a dopaminergic deficit in movement regulation. Movement disorders of different etiologies have been quantified and specified with actometry. We compared 10 AD patients with 10 healthy controls, measuring their rest-activities by actometry. The lower limb motor activity was significantly higher in the AD group. They also displayed a rhythmic, periodic movement pattern similar to akathisia. These findings suggest a hypothesis of idiopathic akathisia and a special sensitivity to adverse effects of neuroleptic drugs.     

Psychiatric drug trials and placebo

The placebo-controlled trial has been the standard method to demonstrate efficacy and safety of drugs. The trials are regulated by standards and principles that aim to safeguard patient safety and to ensure the faultless availability of reliable information about the object of the survey. The use of a placebo group in clinical drug trials is still as well founded as ever, and is especially important in conditions where the severity of the disorder is associated with variation in time, the possibility of a spontaneous recovery, or in conditions involving a significant proportion of subjective experience. In this systematic review, the present guidelines for developing new compounds for psychiatric disorders are discussed.     

Nephrin is specifically located at the slit diaphragm of glomerular podocytes

We describe here the size and location of nephrin, the first protein to be identified at the glomerular podocyte slit diaphragm. In Western blots, nephrin antibodies generated against the two terminal extracellular Ig domains of recombinant human nephrin recognized a 180-kDa protein in lysates of human glomeruli and a 150-kDa protein in transfected COS-7 cell lysates. In immunofluorescence, antibodies to this transmembrane protein revealed reactivity in the glomerular basement membrane region, whereas the podocyte cell bodies remained negative. In immunogold-stained thin sections, nephrin label was found at the slit between podocyte foot processes. The congenital nephrotic syndrome of the Finnish type (NPHS1), a disease in which the nephrin gene is mutated, is characterized by massive proteinuria already in utero and lack of slit diaphragm and foot processes. These features, together with the now demonstrated localization of nephrin to the slit diaphragm area, suggests an essential role for this protein in the normal glomerular filtration barrier. A zipper-like model for nephrin assembly in the slit diaphragm is discussed, based on the present and previous data.     

The Arctic Alzheimer mutation facilitates early intraneuronal Abeta aggregation and senile plaque formation in transgenic mice

The Arctic mutation (APP E693G) is unique, since it is located within the amyloid-beta (Abeta) sequence and leads to Alzheimer's disease (AD). Arctic Abeta peptides more easily form Abeta protofibrils in vitro, but little is known about the pathogenic mechanism of the Arctic mutation in vivo. Here, we analyzed APP transgenic mice with both the Swedish and Arctic mutations (tg-APPArcSwe) and transgenic mice with the Swedish mutation alone (tg-APPSwe). Intense intraneuronal Abeta-immunoreactive staining was present in young tg-APPArcSwe mice, but not in tg-APPSwe mice. Intracellular Abeta aggregates in tg-APPArcSwe were strongly stained by antibodies recognizing the N-terminus of Abeta, while those recognizing the C-terminus of Abeta stained weakly. The Abeta aggregates inside neurons increased with age and predated extracellular Abeta deposition in both tg-APPArcSwe and tg-APPSwe mice. Senile plaque deposition was markedly accelerated in tg-APPArcSwe mice, as compared to tg-APPSwe mice. We conclude that the Arctic mutation causes AD by facilitating amyloidosis through early accumulation of intracellular Abeta aggregates in association with a rapid onset of senile plaque deposition.     

Dream emotions: a comparison of home dream reports with laboratory early and late REM dream reports

The aim of this study was to compare the emotional content of dream reports collected at home upon morning awakenings with those collected in the laboratory upon early and late rapid eye movement (REM) sleep awakenings. Eighteen adults (11 women, seven men; mean age = 25.89 ± 4.85) wrote down their home dreams every morning immediately upon awakening during a 7‐day period. Participants also spent two non‐consecutive nights in the sleep laboratory where they were awoken 5 min into each continuous REM sleep stage, upon which they gave a verbal dream report. The content of a total of 151 home and 120 laboratory dream reports was analysed by two blind judges using the modified Differential Emotions Scale. It was found that: (1) home dream reports were more emotional than laboratory early REM dream reports, but not more emotional than laboratory late REM dream reports; (2) home dream reports contained a higher density of emotions than laboratory (early or late REM) dream reports; and (3) home dream reports were more negative than laboratory dream reports, but differences between home and early REM reports were larger than those between home and late REM reports. The results suggest that differences between home and laboratory dream reports in overall emotionality may be due to the time of night effect. Whether differences in the density of emotions and negative emotionality are due to sleep environment or due to different reporting procedures and time spent in a sleep stage, respectively, remains to be determined in future studies.     

Screening for cardiovascular risk factors and self-rated health in a community setting: a cross-sectional study in Finland

Background

Self-rated health is an independent predictor of mortality. However, general health checks in populations unselected for disease or risk factors have not been shown to reduce mortality or morbidity.

Aim

To describe new comorbidities and cardiovascular risk factors in apparently healthy people and to relate this to their self-rated health.

Design and setting

A targeted screening programme identified 462 middle-aged people with cardiovascular risk factors without previously diagnosed chronic disease in a Finnish community in 2005–2006.

Method

Home blood pressure monitoring, oral glucose tolerance test, estimated glomerular filtration rate, and ankle brachial index were used to detect previously undiagnosed conditions. The Short-Form Health Survey and Beck’s Depression Inventory were completed by participants before the diagnostic tests were performed.

Results

The prevalence of previously undiagnosed disease was: hypertension 113/462 (24% [95% confidence interval {CI} = 21% to 29%]), diabetes 19/462 (4% [95% CI = 2% to 6%]), renal insufficiency 23/462 (5% [95% CI = 3% to 7%]), and peripheral arterial disease 17/462 (4% [95% CI = 2% to 5%]). Of the 139 participants who regarded their health as ‘fair–poor’, 60 (43%) had a previously undetected condition affecting their vasculature.

Conclusion

Out of the screen-detected apparently healthy cardiovascular risk subjects, one in three had undiagnosed hypertension, diabetes, peripheral arterial disease, or renal insufficiency. Those individuals experiencing ill health tended to be at high risk of cardiovascular problems.     

Secular trend in candidemia and the use of fluconazole in Finland, 2004-2007

Background  

In a previous study we observed an increasing trend in candidemia in Finland in the 1990s. Our aim was now to investigate further population-based secular trends, as well as outcome, and evaluate the association of fluconazole consumption and prophylaxis policy with the observed findings.