Clinical characteristics and outcome of pregnancy in women with gestational hyperglycaemia with and without antibodies to beta-cell antigens.

AIMS: To evaluate the prevalence of beta-cell autoantibodies in women with gestational diabetes and impaired glucose tolerance, and identify clinical characteristics differentiating hyperglycaemic patients with and without autoantibodies. METHODS: One hundred and twenty-three pregnant patients with gestational diabetes, 84 with impaired glucose tolerance and 290 with normoglycaemia were evaluated for anti-islet cell antibodies, glutamic acid decarboxylase (GAD) autoantibodies, and the components of the metabolic syndrome. RESULTS: Autoantibody positivity was 8.9%, 17.9% and 0.3% in patients with diabetes, impaired tolerance and normoglycaemia, respectively. Hyperglycaemic patients with autoantibodies had lower body mass index, waist, weight gain at the time of the screening test and a lower percentage of previous pregnancies than those without autoantibodies. In addition, their fasting insulin values were significantly lower and inversely related to the presence of autoantibodies (odds ratio (OR) = 0.64; 95% confidence interval (CI) 0.42-0.96), the lowest values being found in anti-GAD+ patients. Autoantibody-positive women with diabetes were more frequently treated with insulin than negative patients (OR = 7.21; 95% CI 1.85-28.08). CONCLUSIONS: Autoantibody-positive women with gestational hyperglycaemia displayed fewer features of insulin resistance and required more frequent insulin therapy than negative women and presumably had presymptomatic Type 1 diabetes. If this conclusion is corroborated by the follow-up of larger series, clinical and immunological distinction of types of gestational hyperglycaemia would be useful.     

The neck of caveolae is a distinct plasma membrane subdomain that concentrates insulin receptors in 3T3-L1 adipocytes

Insulin receptors (IRs) segregate on plasma membrane microvilli, but in cells devoid of microvilli, such as adipocytes, the localization of IRs is a matter of controversy. In the present study, we examined the distribution of IRs in the plasma membrane of 3T3-L1 adipocytes. Quantitative electron microscopy indicates that IRs are predominantly associated with the neck, but not the bulb, of caveolae. Caveola necks represent distinct microdomains of the plasma membrane. Indeed, as shown by freeze-fracture analysis, intramembrane particles are concentrated as necklaces around the craters of caveolae. In addition, subcellular fractionation suggests that the neck and the bulb of caveolae present a different resistance to detergent solubility. Finally, cytoskeletal components, including actin, are highly enriched in the membrane area underlying the neck part of caveolae. IRs coimmunoprecipitate with cytoskeletal components, and disruption of the actin cytoskeleton alters IRs expression, localization, and signaling, thus supporting the notion that caveola necks are involved in intracellular signaling by IRs. Together, these results suggest that cytoskeletal proteins anchor IRs to microdomains in the caveola necks of 3T3-L1 adipocytes. By homology with IR localization in other cell types, we suggest that the necks of caveolae may represent the counterpart of microvillar domains in cells poor in microvilli such as adipocytes and that they play an important role as signaling platforms.     

Dexamethasone-containing PLGA superparamagnetic microparticles as carriers for the local treatment of arthritis

Superparamagnetic iron oxide nanoparticles (SPIONs) are attractive materials that have been widely used in medicine for diagnostic imaging and therapeutic applications. In our study, SPIONs and the corticosteroid dexamethasone acetate (DXM) are co-encapsulated into PLGA microparticles for the aim of locally treating inflammatory conditions such as arthritis. The magnetic properties conferred by the SPIONs could help to maintain the microparticles in the joint with an external magnet. The aim of this study was to investigate the interaction between magnetic microparticles and human synovial fibroblasts in terms of microparticle uptake (FACS, confocal and optical microscopy), internalization mechanism (Prussian Blue staining, TEM, immunofluorescence), cell toxicity (MTT) and tissue reaction after intra-articular injection (histology). The results show that the microparticles have an excellent biocompatibility with synoviocytes and that they are internalized through a phagocytic process, as demonstrated by fluorescence-activated cell sorting and morphological analyses of cells exposed to microparticles. Histological analysis showed that the prepared microparticles did not induce any inflammatory reaction in the joint. This type of carrier could represent a suitable magnetically retainable intra-articular drug delivery system for treating joint diseases such as arthritis or osteoarthritis.     

Daytime vigilance and quality of life in epileptic patients treated with vagus nerve stimulation

OBJECTIVES: The goal of this study was to determine if vagus nerve stimulation (VNS) has any effect on daytime vigilance and perceived sense of well-being. METHODS: Multiple Sleep Latency Tests (MSLTs) were performed and visual reaction times (VRTs) obtained in eight epileptic patients before and during treatment with VNS. Prior to VNS initiation patients' baseline MSLT and VRT scores were recorded. Six months after VNS was initiated, treatment MSLT and VRT scores were obtained. A group of 12 age-matched healthy subjects served as controls. In addition, there was a global evaluation of well-being at baseline and during a follow-up of 6 months. RESULTS: As expected, patients evaluated both at baseline and during VNS showed more sleepiness than controls. In this group, baseline sleep latencies on the MSLT were significantly shorter, while VRT latencies were significantly longer than those of controls. After 6 months of VNS, MSLT scores in the eight patients did not change significantly with respect to baseline. However, if the single patient treated with relatively high stimulus intensities (1.75 mA) was excluded from the group and only the seven patients treated with low stimulus intensities (相似文献   

Progressive external ophthalmoplegia and vision and hearing loss in a patient with mutations in POLG2 and OPA1

OBJECTIVE: To describe the clinical features, muscle pathological characteristics, and molecular studies of a patient with a mutation in the gene encoding the accessory subunit (p55) of polymerase gamma (POLG2) and a mutation in the OPA1 gene. DESIGN: Clinical examination and morphological, biochemical, and molecular analyses. SETTING: Tertiary care university hospitals and molecular genetics and scientific computing laboratory. PATIENT: A 42-year-old man experienced hearing loss, progressive external ophthalmoplegia (PEO), loss of central vision, macrocytic anemia, and hypogonadism. His family history was negative for neurological disease, and his serum lactate level was normal. RESULTS: A muscle biopsy specimen showed scattered intensely succinate dehydrogenase-positive and cytochrome-c oxidase-negative fibers. Southern blot of muscle mitochondrial DNA showed multiple deletions. The results of screening for mutations in the nuclear genes associated with PEO and multiple mitochondrial DNA deletions, including those in POLG (polymerase gamma gene), ANT1 (gene encoding adenine nucleotide translocator 1), and PEO1, were negative, but sequencing of POLG2 revealed a G1247C mutation in exon 7, resulting in the substitution of a highly conserved glycine with an alanine at codon 416 (G416A). Because biochemical analysis of the mutant protein showed no alteration in chromatographic properties and normal ability to protect the catalytic subunit from N-ethylmaleimide, we also sequenced the OPA1 gene and identified a novel heterozygous mutation (Y582C). CONCLUSION: Although we initially focused on the mutation in POLG2, the mutation in OPA1 is more likely to explain the late-onset PEO and multisystem disorder in this patient.