Severe case and literature review of primary erythromelalgia: novel SCN9A gene mutation

Erythromelalgia is a rare clinical syndrome characterized by intermittent heat, redness, swelling and pain more commonly affecting the lower extremities. Symptoms are mostly aggravated by warmth and are eased by a cold temperature. In some cases, symptoms can be very severe and disabling. Erythromelalgia can be classified as either familial or sporadic, with the familial form inherited in an autosomal dominant manner. Recently, there has been a lot of progress in studying Na(v)1.7 sodium channels (expressed mostly in the sympathetic and nociceptive small-diameter sensory neurons of the dorsal root ganglion) and different mutations affecting the encoding SCN9A gene that leads to channelopathies responsible for some disorders, including primary erythromelalgia. We present a severe case of progressive primary erythromelalgia caused by a new de novo heterozygous missense mutation (c.2623C>G) of the SCN9A gene which substitutes glutamine 875 by glutamic acid (p.Q875E). To our knowledge, this mutation has not been previously reported in the literature. We also provided a short literature review about erythromelalgia and Na(v) sodium channelopathies.     

Effect of glutamate receptor antagonists on migrating neural progenitor cells

Neurotransmitters such as glutamate are potential regulators of neurogenesis. Interference with defined glutamate receptor subtypes affects proliferation, migration and differentiation of neural progenitor cells. The cellular targets for the actions of different glutamate receptor ligands are less well known. In this study we have combined calcium imaging, measurement of membrane potential, time‐lapse imaging and immunocytochemistry to obtain a spatial overview of migrating mouse embryonic neural progenitor cell‐derived cells responding to glutamate receptor agonists and antagonists. Responses via metabotropic glutamate receptor 5 correlated with radial glial cells and dominated in the inner migration zones close to the neurosphere. Block of metabotropic glutamate receptor 5 resulted in shorter radial glial processes, a transient increase in neuron‐like cells emerging from the neurosphere and increased motility of neuron‐like cells. α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)/kainate receptors are present on the majority of migrating neuronal cells, which with time accumulate at the outer edge of the migration zone. Blocking these receptors leads to an enhanced extension of radial glial processes and a reduced motility of neuron‐like cells. Our results indicate that functional glutamate receptors have profound effects on the motility of neural progenitor cells. The main target for metabotropic glutamate receptor 5 appears to be radial glial cells while AMPA/kainate receptors are mainly expressed in newborn neuronal cells and regulate the migratory progress of these cells. The results suggest that both metabotropic glutamate receptor 5 and AMPA/kainate receptors are of importance for the guidance of migrating embryonic progenitor cells.     

小儿脑瘫的推拿治疗

目的:观察推拿手法治疗小儿脑瘫的疗效.方法:选取背腰部穴区、头颈部穴区、四肢部穴区进行手法治疗;益气健脑、理筋整复.及早发现,及早诊断、及早治疗,达最佳治疗效果.结果:推拿手法可益气通经,健脑补肾,改善头部血液循环,促进血栓吸收,达到治病效果.结论:推拿手法治疗小儿脑瘫可以起到较好的效果,值得推广.     

Ultraviolet B radiation regulates cysteine‐rich protein 1 in human keratinocytes

Background: Cysteine‐rich protein 1 (CRP1) is a growth‐inhibitory cytoskeletal protein that is induced by ultraviolet (UV) C radiation radiation in fibroblasts. Our aim was to investigate the effects of UV radiation on CRP1 in keratinocytes, the main cell type subjected to UV radiation in the human body. Methods: The effects of physiologically relevant doses of UVB radiation on CRP1 protein levels were studied in cultured primary keratinocytes and transformed cell lines (HaCaT, A‐431) by immunoblotting. UVB‐induced keratinocyte apoptosis was assessed by flow cytometry and monitoring caspase activity. Expression of CRP1 in human skin in vivo was studied by immunohistochemistry in samples of normal skin, actinic keratosis (AK) representing UV‐damaged skin and squamous cell carcinoma (SCC), a UV‐induced skin cancer. Results: CRP1 expression increased by UVB radiation in primary but not in immortalized keratinocytes. Upon high, apoptosis‐inducing doses of UV radiation, CRP1 was cleaved in a caspase‐dependent manner. In normal skin, CRP1 was expressed in smooth muscle cells, vasculature, sweat glands, sebaceous glands and hair root sheath, but very little CRP1 was present in keratinocytes. CRP1 expression was elevated in basal cells in AK but not in SCC. Conclusion: CRP1 expression is regulated by UVB in human keratinocytes, suggesting a role for CRP1 in the phototoxic responses of human skin.     

Scintigraphic head-to-head comparison between 99mTc-WBCs and 99mTc-LeukoScan in the evaluation of inflammatory bowel disease: a pilot study

Scintigraphy with technetium-99m labelled white blood cells (WBCs) is routinely used in our hospital for the assessment of inflammatory bowel disease (IBD). The main disadvantages of this diagnostic tool are its time-consuming nature and the handling of blood itself. 99mTc-LeukoScan is a relatively new, easily prepared agent that is used for the detection of osteomyelitis. To assess its value in IBD, a scintigraphic head-to-head comparison was performed between 99mTc-LeukoScan and 99mTc-WBCs. 99mTc-LeukoScan scintigraphy was performed in six patients with clinically active IBD and increased uptake on 99mTc-WBC images. The interval between the scintigraphic studies ranged from 2 to 7 days, and endoscopy was subsequently performed to confirm active IBD. In three out of six patients with increased uptake on the 99mTc-WBC scans, 99mTc-LeukoScan images showed very discreet activity in the bowel, but the sites did not correspond with the inflammation sites seen on 99mTc-WBC scintigraphy and found at endoscopy. In the other three patients, 99mTc-LeukoScan scintigraphy revealed a physiological distribution but no abnormalities. In conclusion, 99mTc-LeukoScan is not an alternative agent for the assessment of IBD. A prospective study is not justified owing to the false-negative results.     

Decreased S100-beta protein in schizophrenia: preliminary evidence

The S100 proteins are a family of calcium-binding proteins found in the central and peripheral nervous systems of vertebrates. S100beta, the most abundant member of this family in the CNS, mediates calcium signal transduction, and shows neurotrophic, gliotrophic and mitogenic actions that influence the development and maintenance of the nervous system. Another member of the S100 family (S100A10) was found to modulate phospholipid turnover by inhibiting the activity of enzyme phospholipase A2 (PLA2). We determined the concentration of S100beta protein in the plasma of 23 medicated schizophrenic patients and 23 healthy controls. S100beta protein accounts for 96% of the total S100 in the brain. Schizophrenic patients showed reduced S100beta concentrations (p=0.003), and this finding was not related to clinical variables or to intake of antipsychotic medication. Decreased S100beta could be related to the findings of increased PLA2 activity and to brain maldevelopment in schizophrenia. These results are discussed further with respect to the role of adenosine in S100beta release.     

Vulvar carcinoma presenting during pregnancy,associated with recurrent bone marrow hypoplasia: a case report and literature review

BACKGROUND: Carcinoma of the vulva has predominantly been a disease of the elderly. Although occasionally it occurs in women under the age of 40 years, carcinoma of the vulva has been rarely diagnosed in pregnancy. Bone marrow hypoplasia can occur as a transient, pregnancy-related event; however, the recurrence of this pathology in future pregnancies is quite rare in the literature. CASE: A 29-year-old woman in her second pregnancy that was complicated by bone marrow hypoplasia had developed a squamous vulvar carcinoma. Each of these two conditions are quite rare in pregnancy, they may have occurred by chance, but there is a hypothetical possibility that bone marrow hypoplasia is an autoimmune disorder, with vulvar carcinoma occurring as a further complication in this immunoimpaired individual. CONCLUSION: This case also emphasizes the need to consider malignancy as a differential diagnosis in vulvar ulcers occurring in young women.     

Mitochondrial aminoacyl-tRNA synthetases in human disease

Mitochondrial aminoacyl-tRNA synthetases (mtARSs) are essential in the process of transferring genetic information from mitochondrial DNA to the complexes of the oxidative phosphorylation system. These synthetases perform an integral step in the initiation of mitochondrial protein synthesis by charging tRNAs with their cognate amino acids. All mtARSs are encoded by nuclear genes, nine of which have recently been described as disease genes for mitochondrial disorders. Unexpectedly, the clinical presentations of these diseases are highly specific to the affected synthetase. Encephalopathy is the most common manifestation but again with gene-specific outcomes. Other clinical presentations include myopathy with anemia, cardiomyopathy, tubulopathy and hearing loss with female ovarian dysgenesis. Here we review the described mutation types and the associated patient phenotypes. The identified mutation spectrum suggests that only mutation types that allow some residual tRNA-charging activity can result in the described mtARS diseases but the molecular mechanisms behind the selective tissue involvement are not currently understood.