Non-invasive fetal sex determination using real-time PCR.

OBJECTIVE: The aim of this study was to evaluate the specificity and sensitivity of the real-time quantitative PCR method for fetal gender determination in early pregnancy. METHODS: Blood samples were collected from 46 pregnant women prior to amniocentesis. DNA was extracted from maternal plasma using a QIAmp DNA Blood Mini Kit. DNA samples were subjected to real-time quantitative PCR amplification of SRY (as a fetus-specific marker) and beta-globin (as a marker for total plasma DNA) genes. RESULTS: The beta-globin gene sequence was detected in all samples. The SRY gene was detected in 25 of 28 plasma samples from women with male fetuses and in none of the 18 samples from women with female fetuses (sensitivity 89.2% and specificity 100%). The fetal gender was correctly determined in 43 (93.5%) of 46 maternal plasma samples. The concentration of the beta-globin gene ranged from 161 to 25,568 genome-equivalents (GE)/mL (median 1051.1), while the concentration of the SRY gene ranged from 5 to 166 GE/mL (median 27.4). The percentage of free fetal DNA ranged from 0.1% to 46.1% (median 2.0%). CONCLUSION: Amplification of fetal DNA from maternal plasma by real-time quantitative PCR is a promising method for fetal sex determination in early pregnancy. However, further studies are necessary before this procedure can be included into a clinical routine.     

Advances in stem cell therapy for amyotrophic lateral sclerosis

Introduction: Amyotrophic Lateral Sclerosis (ALS) is a progressive, incurable neurodegenerative disease that targets motoneurons. Cell-based therapies have generated widespread interest as a potential therapeutic approach but no conclusive results have yet been reported either from pre-clinical or clinical studies.

Areas covered: This is an integrated review of pre-clinical and clinical studies focused on the development of cell-based therapies for ALS. We analyze the biology of stem cell treatments and results obtained from pre-clinical models of ALS and examine the methods and the results obtained to date from clinical trials. We discuss scientific, clinical, and ethical issues and propose some directions for future studies.

Expert opinion: While data from individual studies are encouraging, stem-cell-based therapies do not yet represent a satisfactory, reliable clinical option. The field will critically benefit from the introduction of well-designed, randomized and reproducible, powered clinical trials. Comparative studies addressing key issues such as the nature, properties, and number of donor cells, the delivery mode and the selection of proper patient populations that may benefit the most from cell-based therapies are now of the essence. Multidisciplinary networks of experts should be established to empower effective translation of research into the clinic.     

Effectiveness of Delayed-release Dimethyl Fumarate on Clinical and Patient-reported Outcomes in Patients With Relapsing Multiple Sclerosis Switching From Glatiramer Acetate: RESPOND,a Prospective Observational Study

Purpose

The goal of this study was to evaluate clinical outcomes and patient-reported outcomes (PROs) over 12 months in patients with relapsing multiple sclerosis (RMS) who switched from glatiramer acetate (GA) to delayed-release dimethyl fumarate (DMF) 240 mg BID after suboptimal response to GA in real-world clinical practice.

Specifics of Helicobacter pylori infection/NSAID effects in the elderly

The prevalence of Helicobacter pylori (HP) infection increases with age worldwide. Unlike in younger patients, the presentation of peptic disease in the elderly population is subtle and atypical, and thus leads to a delay of diagnosis. Due to comorbidities and advanced age, it results in increased complications, morbidity and mortality. Bleeding and perforation are frequent complications and therefore peptic ulcer in adult patients represents a serious disease. The relationship between the infection caused by HP and the use of non-steroidal anti-inflammatory drugs (NSAID) in the pathogenesis of peptic ulcer disease is still controversial. However these two factors, independently or in synergy, represent the principal cause of peptic ulcer development in the adult population. In patients diagnosed with peptic ulcer caused by HP, more than half take medications containing aminosalicylic acid. Helicobacter pylori infection in elderly NSAID users is associated with an increased ulcer incidence, but not with an increased prevalence of upper digestive tract bleeding. Helicobacter pylori and NSAID consumption are independent and unrelated risk factors for upper gastrointestinal tract bleeding. Eradication of HP is recommended before the initiation of a long-term aspirin administration in elderly patients. Low aspirin dosages are associated with a high risk of ulcer bleeding. The risk of upper gastrointestinal bleeding in elderly patients is significantly higher in the cases of acute abuse of NSAIDs relative to its chronic use. The simultaneous use of NSAID or aspirin and selective serotonin reuptake inhibitors--antidepressants, increases the risk of upper gastrointestinal bleeding. Peptic ulcer disease in the adult population, if combined with old age, presence of serious and/or life- threatening diseases, as well as repeated ulcer bleedings, shows a high mortality rate.     

Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling

Interaction between autoreactive immune cells and astroglia is an important part of the pathologic processes that fuel neurodegeneration in multiple sclerosis. In this inflammatory disease, immune cells enter into the central nervous system (CNS) and they spread through CNS parenchyma, but the impact of these autoreactive immune cells on the activity pattern of astrocytes has not been defined. By exploiting naïve astrocytes in culture and CNS-infiltrated immune cells (CNS IICs) isolated from rat with experimental autoimmune encephalomyelitis (EAE), here we demonstrate previously unrecognized properties of immune cell–astrocyte interaction. We show that CNS IICs but not the peripheral immune cell application, evokes a rapid and vigorous intracellular Ca²⁺ increase in astrocytes by promoting glial release of ATP. ATP propagated Ca²⁺ elevation through glial purinergic P2X7 receptor activation by the hemichannel-dependent nucleotide release mechanism. Astrocyte Ca²⁺ increase is specifically triggered by the autoreactive CD4⁺ T-cell application and these two cell types exhibit close spatial interaction in EAE. Therefore, Ca²⁺ signals may mediate a rapid astroglial response to the autoreactive immune cells in their local environment. This property of immune cell–astrocyte interaction may be important to consider in studies interrogating CNS autoimmune disease.     

Right ventricular metastatic choriocarcinoma obstructing inflow and outflow tract

We operated on a 34-year-old man with a metastatic tumor that extended from the tricuspid valve to the pulmonary valve and obstructed the right ventricle inflow and outflow tracts. The tumor was removed with preservation of the tricuspid valve. Additional chemotherapy was carried out according to the BEPO (etoposid, eisplatin, bleomycin, vincritin) scheme. Histology revealed metastasis of a choriocarcinoma originating from the right testis. Computed tomography performed after 6 months detected no metastases in the lungs. Magnetic resonance imaging showed a thickened right ventricle free wall and apex. The patient is doing well 18 months postoperatively.     

Oncostatin-M induction of vascular endothelial growth factor expression in astroglioma cells

Oncostatin-M (OSM), a hematopoietic cytokine, and vascular endothelial growth factor (VEGF), a quintessential angiogenic signal, are coexpressed in development, cancer and inflammation. Here, we report that OSM treatment of human astroglioma cell lines increases VEGF levels by approximately threefold. Interleukin-1beta (IL-1beta), in combination with OSM, induces up to sevenfold higher VEGF expression, without significantly inducing VEGF on its own. Specifically examining the OSM contribution to VEGF expression, neutralizing antibodies to OSM receptor subunits gp130 and OSMRbeta, but not LIFRbeta, inhibited OSM induction of VEGF, indicating that the OSM-specific receptor OSMRbeta/gp130 transduces the OSM signal for VEGF synthesis. OSM induction of VEGF promoter activity maps to the (-1171, -786) region of the VEGF promoter, which contains a STAT-3-binding site. STAT-3 is indeed essential for this response, since overexpression of a dominant-negative STAT-3 blocks OSM induction of VEGF promoter activity, as well as endogenous VEGF expression. Finally, we demonstrate that OSM is expressed in glioblastoma multiforme tumor biopsies, a particularly malignant form of brain tumor. This novel mechanism of VEGF regulation in astroglioma cells may be active in pathophysiological states where both OSM and IL-1beta are present.