Does Senna Extract Promote Growth of Aberrant Crypt Foci and Malignant Tumors in Rat Colon?

Current evidence suggests that aberrant cryptfoci (ACF) can be used to evaluate agents for theirpotential colon carcinogenic activity. The aim of thepresent study was to determine whether senna pod extract (SE) itself induces ACF and tumors in the ratcolon or increases the development of ACF and tumorsinduced by azoxymethane (AOM). A daily administration ofSE 10 mg/kg by mouth for 13-28 weeks produced a weak laxative effect but did not itself causethe appearance of ACF or tumors. The numbers of ACF andtumors induced by AOM were, however, increased by a doseof SE (100 mg/kg) able to induce chronic diarrhea over three months. These resultssuggest that SE does not cause the appearance of ACF ortumors in the rat colon nor does it have a promotingeffect when given to rats at a dose that produceslaxation (10 mg/kg), whereas a diarrhogenic dose (100mg/kg) increases the appearance of tumors induced byAOM.     

Inhibition of the liver expression of arylalkylamine N-acetyltransferase increases the expression of angiogenic factors in cholangiocytes

Background and aims

Reduction of biliary serotonin N-acetyltransferase (AANAT) expression and melatonin administration/secretion in cholangiocytes increases biliary proliferation and the expression of SR, CFTR and Cl^–/HCO₃^– AE2. The balance between biliary proliferation/damage is regulated by several autocrine neuroendocrine factors including vascular endothelial growth factor-A/C (VEGF-A/C). VEGFs are secreted by several epithelia, where they modulate cell growth by autocrine and paracrine mechanisms. No data exists regarding the effect of AANAT modulation on the expressions of VEGFs by cholangiocytes.

Methods

In this study, we evaluated the effect of local modulation of biliary AANAT expression on the cholangiocytes synthesis of VEGF-A/C.

Results

The decrease in AANAT expression and subsequent lower melatonin secretion by cholangiocytes was associated with increased expression of VEGF-A/C. Overexpression of AANAT in cholangiocyte lines decreased the expression of VEGF-A/C.

Conclusions

Modulation of melatonin synthesis may affect the expression of VEGF-A/C by cholangiocytes and may modulate the hepatic microvascularization through the regulation of VEGF-A/C expression regulating biliary functions.     

Rasch analysis of clinical outcome measures in spinal muscular atrophy

Introduction: Trial design for SMA depends on meaningful rating scales to assess outcomes. In this study Rasch methodology was applied to 9 motor scales in spinal muscular atrophy (SMA). Methods: Data from all 3 SMA types were provided by research groups for 9 commonly used scales. Rasch methodology assessed the ordering of response option thresholds, tests of fit, spread of item locations, residual correlations, and person separation index. Results: Each scale had good reliability. However, several issues impacting scale validity were identified, including the extent that items defined clinically meaningful constructs and how well each scale measured performance across the SMA spectrum. Conclusions: The sensitivity and potential utility of each SMA scale as outcome measures for trials could be improved by establishing clear definitions of what is measured, reconsidering items that misfit and items whose response categories have reversed thresholds, and adding new items at the extremes of scale ranges. Muscle Nerve 49 :422–430, 2014     

Neither too much,nor too little. The dilemma of identifying personality disorders in adolescents patients with self-reports

The study aimed to compare methods of identification of Personality Disorders (PD) in adolescent patients with psychiatric disorders. A sample of 120 Spanish adolescents with clinical disorders was assessed using the International Personality Disorder Examination (IPDE) interview, its Screening Questionnaires (IPDE-SQ) comprising the ICD-10 and DSM-IV modules, and also the Temperament Character Inventory (TCI) to identify risk of PD. The IPDE-SQ identified a risk of PD around 92–97% of the sample; 61.7% when adjusting the stricter cut-off points. The TCI showed a PD risk of 20%, whereas the prevalence of PD identified by the IPDE clinical interview was around 36–38%. The differences between the IPDE, IPDE-SQ and TCI were significant, and a low agreement among instruments was obtained. Large discrepancy between self-report instruments in identifying PD with regard to the clinical interview raises several questions concerning the use of these instruments in clinical settings on adolescents with psychiatric disorders.