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Biomedical subjects

A Samara

Publications and source records attributed to A Samara.

5 recordsLinked to original sources
PubMed2005

Factors involved in the migration of neuroendocrine hypothalamic neurons.

Neuroendocrine control of physiological functions needs a complex developmental organisation of the hypothalamic parvicellular neurons, which synthesise and release hypophysiotropic hormones. Among the hypothalamic neuroendocrine cells, Gonadotropin-releasing hormone (GnRH) neurons represent a unique class; they are generated in the olfactory placode and, during embryonic life, migrate to the septo/hypothalamic region along terminal and vomeronasal nerves. At this level GnRH neurons undergo terminal differentiation and start to release GnRH to modulate the secretion of pituitary gonadotropins. All these steps are under the strict control of several developmental cues and their defect might represent a cause of clinical disorders. A number of factors have been proposed to be involved in the migration of GnRH neurons, but their role is still unclear. By using gene knockout techniques it has been found that mice carrying a targeted deletion of Ebf2 gene, a component of Olf/Ebf bHLH transcription factors, show a defective migration of GnRH neurons, providing the first evidence of a mouse model of such defect. Since the investigation of GnRH neurons is hindered by their peculiar anatomical distribution, other studies has been forwarded by the availability of immortalized GnRH-expressing neurons (GN11 cells) that retain a strong chemomigratory response "in vitro". Among the factors analysed, we found that hepatocyte growth factor/scatter factor (HGF/SF) and vascular endothelial growth factor (VEGF) induce specific chemotaxis of GN 11 neurons, suggesting that migratory signals can arise from nasal mesenchyme and from the concomitant vasculogenesis. Finally, anosmin-1 (the product of the gene responsible of the X-linked form of Kallmann's disease) was found to induce a significant chemotactic response of GN11 cells, confirming a permissive/instructive role of KAL1 gene product in the migratory behaviour of GnRH neurons. In conclusion, the migration of the GnRH neurons appears to be a complex process, which involves the interplay of multiple molecular cues. These studies may provide new insights on the etiopathogenesis of the large proportion of reproductive dysfunctions that affect humans and could provide novel insights on common biochemical events controlling neuronal development and migration.

Animals↗
PubMed1987

Induction of differentiation in human myeloid leukemic cells by T-2 toxin and other trichothecenes.

Trichothecenes are sesquiterpen mycotoxins characterized by the tetracyclic 12,13-epoxytrichothec-9-ene skeleton. We determined the effect of these mycotoxins on the growth and differentiation of the human acute promyelocytic leukemia (HL-60) cell line. Sixteen natural and semisynthetic trichothecenes were tested at concentrations of 0.2-60,000 ng/ml. The cytotoxicity exerted by these compounds varied: e.g., roridin A was found to be toxic at 1 ng/ml, whereas T-2 palmitate was not toxic even at 1 microgram/ml. These compounds varied also in their potential to induce differentiation: 9,10-epoxy T-2 toxin and T-2 toxin induced differentiation at concentrations of 2-5 ng/ml, while 9,10-dihydro T-2 toxin was effective only at 100 ng/ml. Other trichothecenes (e.g., verrucarin A and verrucarol) did not induce differentiation at either subtoxic or toxic concentrations. Cell differentiation was always associated with cytotoxicity; optimal concentrations for induction of differentiation were usually 30-60% of the toxic concentrations. The HL-60 cell population was found to be heterogenous with respect to the ability to differentiate in response to trichothecenes, while in some clones up to 70% of the cells underwent differentiation, and other clones were completely resistant. The latter clones could, however, be induced to differentiate by other agents such as retinoic acid, dimethyl sulfoxide and 12-O-tetradecanoylphorbol-13-acetate. Some of the inducible clones differentiated into neutrophilic granulocytes while others into mature macrophages. Thus, a single trichothecene could induce differentiation into either cell types, depending on the clone used. This study presents a new group of differentiation inducers. Further investigation is required to evaluate their possible therapeutic application.

Cell Differentiation↗
PubMed1986

Efficacy of auranofin as demonstrated by improvement in clinical parameters and decrease in anti-inflammatory usage: a long-term, multicenter study.

An open, noncomparative study at 8 rheumatology centers in Brazil assessed the efficacy and safety of auranofin (AF) when given for up to 24 months. The study enrolled 80 patients with classic or definite rheumatoid arthritis (RA); disease was severe in 20 (25%), moderate in 55 (69%), and mild in 5 (6%). Patients received auranofin, 3 mg twice daily, and varying doses of anti-inflammatory drugs (aspirin, nonsteroidal anti-inflammatory drugs, and corticosteroids). Sixty patients (75%) completed the full 24 months of therapy. No patients were withdrawn from therapy because of insufficient therapeutic effect. There was statistically significant improvement (p less than 0.001) in 9 clinical parameters of disease activity, evident as early as 3 months after beginning AF therapy, increasing steadily over 12 months, and remaining at improved levels for another 12 months. Improvements in some parameters were particularly striking. By 24 months, assessment of well-being had increased by 150%, intensity of pain had decreased by 66%, and duration of morning stiffness had decreased by 78%. The average daily dose of anti-inflammatory drugs also decreased over time. The safety profile of AF was similar to that found in comparable trials. Ten patients (12.5%) were withdrawn because of adverse events: 6 for diarrhea (7.5%), 2 for proteinuria (2.5%), and 1 each for pruritus and anemia (1.25%). Adverse events occurred in 24 of 80 patients; some reported more than one adverse event. The most common adverse events were loose stools (20 patients) or diarrhea (11 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Rofecoxib, a new cyclooxygenase 2 inhibitor, shows sustained efficacy, comparable with other nonsteroidal anti-inflammatory drugs: a 6-week and a 1-year trial in patients with osteoarthritis. Osteoarthritis Studies Group.

INTRODUCTION: Rofecoxib, a cyclooxygenase 2 inhibitor (sometimes known as a specific cyclooxygenase 2 inhibitor or Coxib), is used in osteoarthritis (OA). Published information indicates rofecoxib's improved gastrointestinal safety profile over nonselective nonsteroidal anti-inflammatory agents (NSAIDs). OBJECTIVE: To evaluate the efficacy and safety of rofecoxib in treating OA in 2 studies. METHODS: Two randomized, double-blind, parallel-group studies in patients with OA of the knee or hip were conducted using identical entry criteria and end points. A 6-week placebo-controlled trial in 736 patients compared 12.5 and 25 mg of rofecoxib once daily with 800 mg of ibuprofen 3 times daily, and a 1-year study compared 12.5 and 25 mg of rofecoxib once daily with 50 mg of diclofenac 3 times daily in 693 patients. RESULTS: Rofecoxib, at 12.5 and 25 mg, demonstrated efficacy clinically comparable with ibuprofen, assessed by 3 primary end points according to predefined comparability criteria. Both rofecoxib doses and ibuprofen provided significantly greater efficacy than placebo on all primary end points at 6 weeks. Both rofecoxib doses and diclofenac showed similar efficacy over 1 year. All treatments were well tolerated. CONCLUSIONS: Rofecoxib is effective in treating OA with once-daily dosing for 6 weeks and 1 year. Rofecoxib was generally safe and well-tolerated in OA patients for 6 weeks and 1 year. Arch Fam Med. 2000;9:1124-1134

Adult↗