The management of osteoarthritis. Landing on the ground of reality

SIR, The EULAR 2003 recommendations for knee osteoarthritis(OA) include a table with an ‘evidence based final setof 10 recommendations’ [1]. Recommendation number 8 states:‘SYSADOA [symptomatic slow-acting drugs in osteoarthritis](glucosamine sulphate, chondroitin sulphate, ASU [avocado andsoya unsaponifiables], diacerein, and hyaluronic acid) havesymptomatic effects and may modify structure’. Concerningthe modifying effect of glucosamine sulphate (GS), the authorsrefer to just one study (supported by a pharmaceutical manufacturer),including 106 patients with     

Autonomic neuropathy and gastrointestinal motility disorders in children and adolescents with type 1 diabetes mellitus

INTRODUCTION: There is little information on the gastrointestinal motility abnormalities and autonomic neuropathy of children with gastrointestinal symptoms and type 1 diabetes mellitus (T1DM). METHODS: The authors studied 33 consecutive patients (mean age, 15.3 years; 13 males) with T1DM (median duration, 7.7 years) attending the outpatient clinic because of chronic dyspepsia (CD; n = 14), or chronic constipation (CC; n = 19), and 48 consecutive non-T1DM patients (mean age, 13.7 years; 18 males), who presented with similar symptoms (18 with CD; 30 with CC). Fasting serum motilin concentrations and cardiovascular autonomic function tests (CAFT) were assessed and compared with those of age- and gender-matched healthy control subjects. Gastric emptying half time (GE t1/2) of a solid meal and mouth-to-anus transit time (MATT) were measured in patients with CD and CC, respectively. RESULTS: CAFT was comparable between patients with T1DM and healthy control subjects. GE t1/2 and MATT were not different between T1DM patients and non-T1DM patients with CD and CC, respectively. However, a marginally significant positive correlation was found in the patients with T1DM between GE t1/2 and blood glucose concentrations (R = 0.54; P = 0.08). In addition, serum motilin concentrations were significantly lower in patients with T1DM compared with healthy control subjects (P < 0.0005), and in patients with T1DM and higher serum glucose concentrations compared with those with lower serum glucose concentrations (P = 0.03). CONCLUSION: Autonomic neuropathy is not an etiological factor of gastrointestinal symptoms in children and adolescents with diabetes. Mild or moderate hyperglycemia does not affect gastrointestinal motility.     

Fluorometric measurements of conformational changes in glutamate transporters

Glutamate transporters remove glutamate from the synaptic cleft to maintain efficient synaptic communication between neurons and to prevent extracellular glutamate concentrations from reaching neurotoxic levels (1). It is thought that glutamate transporters mediate glutamate transport through a reaction cycle with conformational changes between the two major access states that alternatively expose glutamate-binding sites to the extracellular or to the intracellular solution. However, there is no direct real-time evidence for the conformational changes predicted to occur during the transport cycle. In the present study, we used voltage-clamp fluorometry to measure conformational changes in the neuronal excitatory amino acid transporter (EAAT) 3 glutamate transporter covalently labeled with a fluorescent reporter group. Alterations in glutamate and cotransported ion concentrations or in the membrane voltage induced changes in the fluorescence that allowed detection of conformational rearrangements occurring during forward and reverse transport. In addition to the transition between the two major access states, our results show that there are significant Na(+)-dependent conformational changes preceding glutamate binding. We furthermore show that Na(+) and H(+) are cotransported with glutamate in the forward part of the transport cycle. The data further suggest that an increase in proton concentrations slows the reverse transport of glutamate, which may play a neuro-protective role during ischemia.     

Improved outcome of polyoma virus allograft nephropathy with early biopsy

Polyoma virus allograft nephropathy often results in accelerated graft loss despite reduction of immunosuppression and/or treatment with antiviral agents. Irreversible renal fibrosis due to late diagnosis is likely to be one of the important causes of treatment failure. Early biopsy in 14 patients resulted in stable graft function after a mean follow-up of 22 months.     

Prolongation of the Intestinal Viability Using Oxygenated Perfluorocarbon in an Experimental Model of Acute Intestinal Ischemia

OBJECTIVES: Liquid perfluorocarbons (PFCs) are well known for their capability to carry respiratory gases. The aim of this study was to evaluate the effectiveness of oxygenated F-Decalin on the intestinal viability, in an experimental model of acute intestinal ischemia. MATERIAL AND METHODS: Thirty-six rabbits were subjected to 8h intestinal ischemia by ligation of the superior mesenteric artery (subgroups 1), the mesenteric vein (subgroups 2) or both vessels (subgroups 3). The animals were divided into three groups: (a) Control (ischemia alone), (b) PFC-O2 (ischemia plus infusion of oxygenated F-Decalin) and (c) PFC (ischemia plus infusion of not-oxygenated F-Decalin). Intestinal biopsies from four different sites and blood samples for serum enzymes measurements were taken at 2, 4, 6 and 8 h. All tissue sections were examined blindly under light microscope. Sections from the specimens were taken at 4 and 8 h, and examined blindly under the electron microscope. Statistical analysis was performed by non-parametric Kruskal Wallis test. RESULTS: Using light microscope, the observed intestinal damages to the sections from Control and PFC groups were severe at 4 h and destructive after 8 h. On the contrary, minimal injuries were observed in the biopsies from PFC-O2 group at 4 and even after 8 h of ischemia. These findings were confirmed by the electron microscope study and correlated to the serum enzymes measurements. CONCLUSIONS: These results suggest that intestinal viability could be prolonged after acute ischemia using oxygenated perfluorocarbons and this could be a promising pretreatment modality for a variety of mesenteric ischemic forms.