Methylamine but not mafenide mimics insulin-like activity of the semicarbazide-sensitive amine oxidase-substrate benzylamine on glucose tolerance and on human adipocyte metabolism

It has been reported that benzylamine reduces blood glucose in rabbits, stimulates hexose uptake, and inhibits lipolysis in mouse, rabbit, and human adipocytes. In the presence of vanadate, benzylamine is also able to improve glucose disposal in normoglycaemic and diabetic rats. Such insulin-mimicking properties are the consequence of hydrogen peroxide production during benzylamine oxidation by semicarbazide-sensitive amine oxidase (SSAO). The aim of the study was to determine whether other SSAO-substrates could share such potential antidiabetic properties. Thus, mafenide, a synthetic antimicrobial sulfonamide structurally related to benzylamine, and which has been recently reported to interact with SSAO, was tested in the above mentioned models, in parallel with methylamine, a proposed endogenous SSAO-substrate. All tested amines stimulated glucose uptake and inhibited lipolysis in rat and mouse fat cells. Methylamine and benzylamine, but not mafenide, reduced the hyperglycaemic response during a glucose tolerance test in rabbits while the three amines tested were devoid of insulin-releasing activity under both in vivo and in vitro conditions. In human adipocytes, mafenide did not stimulate glucose transport since it was not a high-affinity substrate for SSAO and generated less hydrogen peroxide than benzylamine or methylamine. Therefore, mafenide could not be considered as an antidiabetic drug despite being oxidized and exhibiting insulin-mimicking effects in rat and mouse adipocytes. By contrast, the endogenous substrate methylamine improved glucose utilization in all in vitro and in vivo models, leading to consider novel SSAO substrates as drugs with potential anti-hyperglycaemic properties.     

Validation of the Italian Version of the SARC-F Questionnaire to Assess Sarcopenia in Older Adults

Background: SARC-F is a simple sarcopenia screening tool. This study aimed to examine the validity of the Italian version of SARC-F. Methods: A total of 97 elderly individuals (37/60 males/females, 65 years and older) who met the study’s selection criteria were included. SARC-F was translated into the Italian language in a culturally responsive manner. The total score was calculated by adding the scores on the five items. The participants were divided into two groups according to the total score (SARC-F < 4 vs. SARC-F ≥ 4), and their associations with various factors (handgrip test, chair stand test, and Skeletal Muscle Index assessed by DXA) have been examined by gender. In addition, the tool’s validity was analyzed by comparing it with different international working group diagnostic criteria for sarcopenia. Results: The total prevalence of sarcopenia according to the SARC-F was 14.2% and, specifically, 12.8% among men and 14.3% in women. The sensitivity of the SARC-F was (male (M): 11–50% and female (F): 22–36%) medium-low compared with the European, international, and Asian criteria of sarcopenia; however, SARC-F showed a high specificity (M: 77.3–100% and F: 79.5–100%) and a moderate Cronbach’s alpha coefficient of (0.669 (CI95%: 0.358–0.830). The participants in the SARC-F ≥ 4 group had poorer handgrip for EWGSOP2 (p < 0.001) and chair stand (p < 0.001) than the participants in the SARC-F < 4 group. Conclusions: The Italian language version of SARC-F showed high specificity, moderate reliability, and good associations with other predictive tests. The Italian version of SARC-F appears to be a useful screening tool for the diagnosis of sarcopenia in Italian elderly populations.     

Hepatitis C virus-associated hypobetalipoproteinemia is correlated with plasma viral load,steatosis, and liver fibrosis

OBJECTIVES: A relationship between chronic hepatitis C virus (HCV) infection and lipid metabolism has recently been suggested. The aim of this study was to determine the correlation between lipid profile and virology, histologic lesions, and response to alpha interferon therapy in noncirrhotic, nondiabetic patients with hepatitis C. METHODS: A total of 109 consecutive untreated chronic hepatitis C patients were studied to assess the following: 1) the effects of HCV genotype, viral load, steatosis, hepatic fibrosis, and body mass index (BMI) on lipid profile; and 2) whether lipid parameters could predict response to antiviral therapy. RESULTS: The control group showed a significantly higher apolipoprotein B (apoB) concentration compared with patients with chronic hepatitis C. Hypobetalipoproteinemia (apo B <0.7 g/L) was found in 27 (24.7%) chronic HCV patients and in five (5.3%) control subjects (p = 0.0002). Levels of apo B were negatively correlated with steatosis and HCV viral load (r = -0.22; p = 0.03). This last correlation was strong for non-1 genotype and genotype 3 (r = -0.48; p = 0.0005, and r = -0.47; p = 0.007, respectively) but was not found in genotype 1. In multivariate analysis, low apo B concentration was significantly associated with fibrosis grade 2 or 3 versus grade 0 or 1 (p < 0.001), steatosis >5% (p < 0.001), low body mass index (p < 0.001), and high HCV viral load (p < 0.014). No correlation was found in the 76 treated patients between apo B and response to interferon therapy. CONCLUSIONS: In chronic HCV patients, hypobetalipoproteinemia occurs already in the early stages of HCV infection before the development of liver cirrhosis. The correlation between apo B levels and HCV viral load seems to confirm the interaction between hepatitis C infection and beta-lipoprotein metabolism.     

Visceral larva migrans mimicking lymphoma

We report a case of visceral larva migrans in an adult with fever, night sweats, weight loss, hilar and mediastinal lymphadenopathy, bilateral pleural effusion, and eosinophilia-mimicking lymphoma. Visceral larva migrans was diagnosed subsequently because of negative findings for malignancy and positive serologic test result for Toxocara canis. Progressive improvement was observed with albendazole therapy.     

Potential efficacy of enzyme replacement and substrate reduction therapy in three siblings with Gaucher disease type III

Summary  We report three siblings with Gaucher disease type III, born between 1992 and 2004. During this period, new developments resulted in different potential therapies, changing clinical practice. The two eldest siblings received enzyme replacement therapy (ERT) from the age of 24 and 5 months respectively, later followed by an increase in dosage. ERT was combined with substrate reduction therapy (SRT) from the ages of 12 and 8 years, respectively. In the youngest sibling the combination of high-dose ERT and SRT was given from the age of 5 months. The two eldest siblings showed significant neurological impairment from the age of 1.5 years, starting with a convergent strabismus and partial oculomotor apraxia, followed by cognitive decline and an abnormal EEG and BAER. In contrast, the neurological development in the youngest sibling is almost completely normal. At the age of 3 years, cognitive development, EEG and BAER are all normal. Disturbed saccadic eye movements, which were already present at the start of therapy, remained stable. In addition to the clinical efficacy, we report on the biochemical response to therapy. Based on our results, the combination of high-dose ERT and SRT should be considered as a possible therapeutic approach for GD III, especially if started at a young age. Further follow-up studies are necessary to explore the long-term therapeutic effects. Competing interests: F.A. Wijburg provides consultancy services for Genzyme Corporation. References to electronic databases: Glucocerebrosidase, EC 3.2.1.45. Gaucher disease type I, OMIM #230800. Gaucher disease type II, OMIM #230900. Gaucher disease type III, OMIM #231000.     

Brain structure in asymptomatic FMR1 premutation carriers at risk for fragile X-associated tremor/ataxia syndrome

Fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset movement disorder affecting FMR1 premutation carriers, is associated with cerebral and cerebellar lesions. The aim of this study was to test whether computational anatomy can detect similar patterns in asymptomatic FMR1 premutation carriers (mean age 46.7 years) with qualitatively normal -appearing grey and white matter on brain MRI. We used a multimodal imaging protocol to characterize brain anatomy by automated assessment of gray matter volume and white matter properties. Structural changes in the hippocampus and in the cerebellar motor network with decreased gray matter volume in lobule VI and white matter alterations of the corresponding afferent projections through the middle cerebellar peduncles are demonstrated. Diffuse subcortical white matter changes in both hemispheres, without corresponding gray matter alterations, are only identified through age × group interactions. We interpret the hippocampal fimbria and cerebellar changes as early alterations with a possible neurodevelopmental origin. In contrast, progression of the diffuse cerebral hemispheric white matter changes suggests a neurodegenerative process, leading to late-onset lesions, which may mark the imminent onset of FXTAS.