Leucine-glycine and carnosine dipeptides prevent diabetes induced by multiple low-dose streptozotocin in experimental model of adult mice

Aims/Introduction Peptides are considered as quasi‐hormones and effective molecules for regulation of the cells function and metabolic disorders prevention. Di‐ and tripeptides with the ability to gastrointestinal absorption have been proposed to prevent diabetes progression. Materials and Methods Small peptides with different sequences of specific amino acids were synthesized based on a solid phase peptide synthesis (SPPS) protocol as well as carnosine (A) and glutathione (B) were examined for the prevention of diabetes induced by multiple low‐dose of streptozotocin (MLDS) in mice. Results The peptides A, Leu‐Gly (D) and Pro‐Pro (F) exhibited a preventive effects on blood glucose elevation and impairment of the signaling and performance of beta cells. The beta cells function assessed by immunofluorescence and blood glucose level in mice exposed to diabetes treated by the peptides A and D was similar to the normal mice. The peptide D prevented from body weight loss caused by diabetes induction. The use of D and A peptides dramatically prevents the incidence of disruption in beta cells signaling by maintaining the natural balance of intracellular Akt‐2 and cAMP. Conclusions The results proved that peptide D (Leu‐Gly) named Hannaneh inhibits the body weight loss caused by diabetes induction. The Hannaneh and carnosine dipeptides with preservation of normal beta cell signalling and anti DPP‐4 activity were prevented from increasing the blood glucose in mice at risk of diabetes. These dipeptides may be regarded as the pharmaceutical agents for the prevention of diabetes

First results of the diagnostic evaluation studies and the clinical efficacy evaluation in the Dutch PACS project

The objective of the studies was to evaluate the diagnostic performance of the image digitizing distribution and display equipment of the installed PACS (Philips) in the Utrecht University Hospital (see also procee-dings SPIE 914, 1988). The diagnostic accuracy was evaluated by means of observer performance studies, using ROC analysis. Three series of films were used: chest phantom radiographs, clinical mammographic films, and clinical head CT's. We compared: original films versus images digitized with a video scanner, and/or original films versus images digitized with a laser scanner. Both scanners have 1024x1024x8 bits output resolution. Four radiologists scored the presence on a 5-point scale. The results of the mammographic and head CT series will be presented in this paper. The results of the diagnostic accuracy studies of the chest radiographs and their specific methodology will be presented in a companion SPIE paper. Goal of the clinical efficacy study is to see if the use of a PACS multimodality viewing station at an internal ward has clinical advantages as compared to the conventional situation. Using PACS integrated with a HIS (including a RIS) more easier and faster information is accessible to the clinicians. In this paper we will describe: the procedures which are needed to evaluate the use of the workstation installed at the internal ward, the development of the user interface with four layers of the Image Management System, and the methodology of evaluation the clinical advantages

Intrinsic carnosine metabolism in the human kidney

Pathophysiology, epidemiology and therapy of agein

First results of the diagnostic evaluation studies and the clinical efficacy evaluation in the Dutch PACS project

The objective of the studies was to evaluate the diagnostic performance of the image digitizing distribution and display equipment of the installed PACS (Philips) in the Utrecht University Hospital (see also procee-dings SPIE 914, 1988). The diagnostic accuracy was evaluated by means of observer performance studies, using ROC analysis. Three series of films were used: chest phantom radiographs, clinical mammographic films, and clinical head CT's. We compared: original films versus images digitized with a video scanner, and/or original films versus images digitized with a laser scanner. Both scanners have 1024x1024x8 bits output resolution. Four radiologists scored the presence on a 5-point scale. The results of the mammographic and head CT series will be presented in this paper. The results of the diagnostic accuracy studies of the chest radiographs and their specific methodology will be presented in a companion SPIE paper. Goal of the clinical efficacy study is to see if the use of a PACS multimodality viewing station at an internal ward has clinical advantages as compared to the conventional situation. Using PACS integrated with a HIS (including a RIS) more easier and faster information is accessible to the clinicians. In this paper we will describe: the procedures which are needed to evaluate the use of the workstation installed at the internal ward, the development of the user interface with four layers of the Image Management System, and the methodology of evaluation the clinical advantages

A Rare Form of Retinal Dystrophy Caused by Hypomorphic Nonsense Mutations in CEP290

Purpose: To identify the gene defect and to study the clinical characteristics and natural course of disease in a family originally diagnosed with oligocone trichromacy (OT), a rare congenital cone dysfunction syndrome. Methods: Extensive clinical and ophthalmologic assessment was performed on two siblings with OT and long-term follow up data were analyzed. Subsequently, whole exome sequencing (WES) and Sanger sequence analysis of CEP290 was performed in the two siblings. Additionally, the identified CEP290 mutations were analyzed in persons with achromatopsia (ACHM) (n = 23) and autosomal recessive or isolated cone dystrophy (CD; n = 145). Results: In the first decade of life, the siblings were diagnosed with OT based on low visual acuity, photophobia, nystagmus, and absent cone response on electroretinography , but with normal color discrimination. Over time, the phenotype of OT evolved to a progressive degenerative disease without any CEP290-associated non-ocular features. In both siblings, two nonsense mutations (c.451C>T; p.(Arg151*) and c.4723A>T; p.(Lys1575*)) in CEP290 were found. Previously, p.(Arg151*) was demonstrated to induce nonsense-mediated alternative splicing events leading to intact open reading frames of the resulting mRNA products (p.(Leu148_Glu165del) and p.(Leu148_Lys172del)). mRNA analysis for p.(Lys1575*) confirmed a suspected hypomorphic character, as exon 36 skipping was observed in a small fraction of CEP290 mRNA, resulting in a 36 aa in-frame deletion (p.(Glu1569_Trp1604del)). No additional cases carrying these variants were identified in the ACHM and CD cohorts. Conclusions: Compound heterozygous hypomorphic mutations in CEP290 may lead to a rare form of cone-dominated retinal dystrophy, a novel phenotype belonging to the CEP290-associated spectrum of ciliopathies. These findings provide insight into the effect of CEP290 mutations on the clinical phenotype

Metabolic imaging of fatty kidney in diabesity : Validation and dietary intervention

Background Obesity and type 2 diabetes have not only been linked to fatty liver, but also to fatty kidney and chronic kidney disease. Since non-invasive tools are lacking to study fatty kidney in clinical studies, we explored agreement between proton magnetic resonance spectroscopy (1 H-MRS) and enzymatic assessment of renal triglyceride content (without and with dietary intervention). We further studied the correlation between fatty kidney and fatty liver. Methods Triglyceride content in the renal cortex was measured by 1 H-MRS on a 7-Tesla scanner in 27 pigs, among which 15 minipigs had been randomized to a 7-month control diet, cafeteria diet (CAF) or CAF with low-dose streptozocin (CAF-S) to induce insulin-independent diabetes. Renal biopsies were taken from corresponding MRS-voxel locations. Additionally, liver biopsies were taken and triglyceride content in all biopsies was measured by enzymatic assay. Results Renal triglyceride content measured by 1 H-MRS and enzymatic assay correlated positively (r = 0.86, P < 0.0001). Compared with control diet-fed minipigs, renal triglyceride content was higher in CAF-S-fed minipigs (137 ± 51 nmol/mg protein, mean ± standard error of the mean, P < 0.05), but not in CAF-fed minipigs (60 ± 10 nmol/mg protein) compared with controls (40 ± 6 nmol/mg protein). Triglyceride contents in liver and kidney biopsies were strongly correlated (r = 0.97, P < 0.001). Conclusions Non-invasive measurement of renal triglyceride content by 1 H-MRS closely predicts triglyceride content as measured enzymatically in biopsies, and fatty kidney appears to develop parallel to fatty liver. 1 H-MRS may be a valuable tool to explore the role of fatty kidney in obesity and type 2 diabetic nephropathy in humans in vivo