Die Ausscheidung des ß-Phenylisopropylamins bei Menschen

Zusammenfassung Wir haben bei vier Versuchspersonen die Ausscheidung in den Harn von -Phenylisopropylamin nach peroraler Eingabe untersucht.15–60% der eingegebenen Menge wurde im Harn unverändert wiedergefunden.Die Ausscheidung kann bis 3 Tage nach der Eingabe nachgewiesen werden.Bei größerer Diurese wird verhältnismäßig mehr des eingegebenen Amins unverändert ausgeschieden.Der Prozentteil des ausgeschiedenen Amins scheint von der Größe der eingegebenen Dosis (5–20 mg) unabhängig zu sein.Tägliche Verabreichung von 5 mg während eines Monats zeigt keine Kumulationswirkung.Nach parenteraler Eingabe kann man ß-Phenylisopropylamin im Magen nachweisen.Aus den Versuchen kann mit Sicherheit geschlossen werden, daß jedenfalls ein Teil des ß-Phenylisopropylamins im Menschenorganismus abgebaut oder umgebildet wird, obwohl dies viel langsamer als im Kaninchenorganismus vor sich geht.     

No evidence of association between mutant alleles of the CYP27B1 gene and multiple sclerosis

An association has previously been reported between susceptibility to multiple sclerosis and the rare mutant alleles of the CYP27B1 gene responsible for autosomal recessive vitamin D–dependent rickets type 1 (VDDR1). In an attempt to replicate this finding, we screened 495 multiplex families and 2,092 single affected families, together with 4,594 cases and 3,583 controls (a total of 17,073 individuals) but were unable to find any evidence supporting this putative association. Our data do not indicate that mutations responsible for VDDR1 influence the risk of developing multiple sclerosis. ANN NEUROL 2013;73:430–432     

Effect of a dietary fiber (beet fiber) on Dimethylhydrazine‐induced colon cancer in wistar rats

The modifying effect of a dietary fiber, Fibeta (beet fiber), on experimentally induced colorectal cancer was studied in Wistar rats. The rats were fed a powdered semisynthetic casein‐based diet in which the carbohydrate pool was substituted with Fibeta as the sole source of fiber. Dimethylhydrazine dihydrochloride (DMH‐2HCI) was used as initiator in a dose of 20 mg/kg body wt and given by gavage once a week for 10 weeks. Throughout the experiment the rats were offered the diets with different levels of fiber in a preinitiation period of 8 weeks, during the initiation, or in a 30‐week postinitiation period. The study was terminated after one year.

A protective effect of the fiber was not found at any stage of the colorectal carcinogenic process. Even though differences (not statistically significant) in tumor incidences were seen, these did not reflect any effect of the high or low fiber intake during the study.

Analysis for volatile fatty acids in cecal content showed that continuous feeding with a fiber‐rich diet resulted in significant increase in most of the volatile fatty acids. The relative change was highest for butyric acid. These findings do not support the hypothesis that butyric acid has a protective effect on colorectal cancer. The tumor yield in the present study was low compared with that reported in the literature, and possible causes for this are discussed.     

Inter-observer reliability of the “Assessment of Motor Repertoire — 3 to 5 Months” based on video recordings of infants

Objective

A detailed analysis of infant motor behaviour can show up indicators for later neurological impairment. The “Assessment of Motor Repertoire — 3 to 5 Months”, which is part of Prechtl's general movement assessment, could potentially be used for this purpose. The aim of the present study was to investigate inter-observer reliability in this instrument.

Method

Video recordings of 24 infants (corrected ages 3 to 5 months, gestational ages 24 to 42 weeks) were analysed by four observers. Kappa and ICC statistics were applied in the reliability analysis.

Results

High to very high inter-observer reliability was found in the assessment of “Fidgety Movements” (kappa 0.75-0.91). Agreement on the “Movement Character” was also high (kappa 0.54-0.84), while the assessment of the “Posture” showed the lowest inter-observer reliability (kappa 0.39-0.56). Moderate to high inter-observer reliability (kappa 0.51-0.84) was achieved in the field “Quality of Other Movements”, and moderate in “Repertoire of Co-Existent Other Movements” (kappa 0.51-0.69).Inter-observer reliability in the assessment of the total “Motor Optimality Score” was very high between all four observers as intraclass correlation coefficient (2,1) was 0.87, and ICCs for the pairwise analyses ranged between 0.80 and 0.94.

Conclusion

Inter-observer reliability in the “Assessment of Motor Repertoire — 3 to 5 Months” was satisfactory in respect of the subcategories and in case of high and low total optimality scores in pairwise assessments. In the total optimality scores, however, there was some inconsistency in the middle range of the scale.     

A well-developed endolysosomal system reflects protein reabsorption in segment 1 and 2 of rat proximal tubules

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A qualitative study of new fathers’ experiences of care in relation to complicated childbirth

ObjectivesThe objective of the study was to describe new fathers’ experiences with care related to complicated childbirth.MethodsA qualitative approach consisting of individual interviews using a semi-structured interview guide with open-ended questions was applied. A purposive sample of eight fathers participated. The interview text was subjected to qualitative thematic content analysis.ResultsAnalysis revealed the following three categories: (1) feeling scared and uncared for during acute situations; (2) appreciating the opportunity to participate in care and becoming a family; and (3) needing continued care. Based on these three categories, a recurring theme was identified: struggling to be recognized by care staff as a partner in the family was revealed.ConclusionAlthough fathers lack support and understanding from care staff, they strive to fulfill their roles as fathers by guarding their families and keeping them together. Caregivers involved in the childbirth process should realize that by acknowledging and encouraging fathers in these roles, they in turn support the entire family unit. Interventions developed for fathers and family care requires further development. Additional research concerning how midwives and critical care nurses (CCNs) view the presence of fathers in the emergency situations that may accompany childbirth is also needed.     

Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies

Mutations of the gene encoding four-and-a-half LIM domain 1 (FHL1) are the causative factor of several X-linked hereditary myopathies that are collectively termed FHL1-related myopathies. These disorders are characterized by severe muscle dysfunction and damage. Here, we have shown that patients with idiopathic inflammatory myopathies (IIMs) develop autoimmunity to FHL1, which is a muscle-specific protein. Anti-FHL1 autoantibodies were detected in 25% of IIM patients, while patients with other autoimmune diseases or muscular dystrophies were largely anti-FHL1 negative. Anti-FHL1 reactivity was predictive for muscle atrophy, dysphagia, pronounced muscle fiber damage, and vasculitis. FHL1 showed an altered expression pattern, with focal accumulation in the muscle fibers of autoantibody-positive patients compared with a homogeneous expression in anti-FHL1–negative patients and healthy controls. We determined that FHL1 is a target of the cytotoxic protease granzyme B, indicating that the generation of FHL1 fragments may initiate FHL1 autoimmunity. Moreover, immunization of myositis-prone mice with FHL1 aggravated muscle weakness and increased mortality, suggesting a direct link between anti-FHL1 responses and muscle damage. Together, our findings provide evidence that FHL1 may be involved in the pathogenesis not only of genetic FHL1-related myopathies but also of autoimmune IIM. Importantly, these results indicate that anti-FHL1 autoantibodies in peripheral blood have promising potential as a biomarker to identify a subset of severe IIM.