Consequences of the 118A>G polymorphism in the OPRMI gene: Translation from bench to bedside?

The 118A>G single nucleotide polymorphism (SNP) in the μ-opioid receptor (OPRM1) gene has been the most described variant in pharmacogenetic studies regarding opioid drugs. Despite evidence for an altered biological function encoded by this variant, this knowledge is not yet utilized clinically. The aim of the present review was to collect and discuss the available information on the 118A>G SNP in the OPRM1 gene, at the molecular level and in its clinical manifestations. In vitro biochemical and molecular assays have shown that the variant receptor has higher binding affinity for β-endorphins, that it has altered signal transduction cascade, and that it has a lower expression compared with wild-type OPRM1. Studies using animal models for 118A>G have revealed a double effect of the variant receptor, with an apparent gain of function with respect to the response to endogenous opioids but a loss of function with exogenous administered opioid drugs. Although patients with this variant have shown a lower pain threshold and a higher drug consumption in order to achieve the analgesic effect, clinical experiences have demonstrated that patients carrying the variant allele are not affected by the increased opioid consumption in terms of side effects

Mitochondrial DNA Backgrounds Might Modulate Diabetes Complications Rather than T2DM as a Whole

Mitochondrial dysfunction has been implicated in rare and common forms of type 2 diabetes (T2DM). Additionally, rare mitochondrial DNA (mtDNA) mutations have been shown to be causal for T2DM pathogenesis. So far, many studies have investigated the possibility that mtDNA variation might affect the risk of T2DM, however, when found, haplogroup association has been rarely replicated, even in related populations, possibly due to an inadequate level of haplogroup resolution. Effects of mtDNA variation on diabetes complications have also been proposed. However, additional studies evaluating the mitochondrial role on both T2DM and related complications are badly needed. To test the hypothesis of a mitochondrial genome effect on diabetes and its complications, we genotyped the mtDNAs of 466 T2DM patients and 438 controls from a regional population of central Italy (Marche). Based on the most updated mtDNA phylogeny, all 904 samples were classified into 57 different mitochondrial sub-haplogroups, thus reaching an unprecedented level of resolution. We then evaluated whether the susceptibility of developing T2DM or its complications differed among the identified haplogroups, considering also the potential effects of phenotypical and clinical variables. MtDNA backgrounds, even when based on a refined haplogroup classification, do not appear to play a role in developing T2DM despite a possible protective effect for the common European haplogroup H1, which harbors the G3010A transition in the MTRNR2 gene. In contrast, our data indicate that different mitochondrial haplogroups are significantly associated with an increased risk of specific diabetes complications: H (the most frequent European haplogroup) with retinopathy, H3 with neuropathy, U3 with nephropathy, and V with renal failure

The incidence of craniomandibular disorders in patients with cervical dysfunctions. A clinico-statistical assessment

The aim of this research was to measure the incidence of craniomandibular disorders in a group of patients with functional-type cervical alterations. The group consisted of 50 patients undergoing treatment for disorders of the cervical sectors of the spine. Each patient was subjected to a medical examination to investigate the presence of CMD signs or symptoms. From the data statistical analysis a higher percentage of cases with muscular and joint pain, limited mouth opening, deviation and deflection, were found in comparison with the percentage found among the general population. This demonstrates an overloading of the entire masticatory apparatus. Joint noise was less frequent, probably due to its exclusion from our sample of patients with arthrosis-type degenerative pathology

A method to improve passive fit of frameworks on implant-supported prostheses: an in vivo study

A die stone jig was evaluated as to its ability to clinically verify the position of the abutment on the master cast. The jig detected misfits in clinical trials, according to the parameters defined in the literatur