Multiple endocrine neoplasia type II (MEN-II) syndrome is an autosomal dominant condition characterized by medullary carcinoma of the thyroid, pheochromocytoma, and parathyroid adenoma. A cytogenetic ...investigation was conducted on 13 MEN-II syndrome patients from four unrelated kindreds and 13 age-matched control subjects for chromosome instability and the chromosome 20 deletion reported in MEN-II syndrome. A significant increase (p less than 0.05) was found in the total number of chromatid and chromosome aberrations in MEN-II cells (12.3%) compared with control cells (6.9%) grown at 96 hours in mitomycin C (20 ng/ml, final concentration). The major difference between the two groups was in chromatid, and not chromosome, aberrations. There was no difference between MEN-II and control individuals in fragile site expression, the number of sister chromatid exchanges or cell kinetics. A blind analysis of high-resolution G-banded chromosomes was performed on blood specimens from 13 MEN-II and seven control individuals. Twelve of 13 MEN-II patients and one of seven control subjects were scored as having a 20p12.2 deletion (chi 2 = 12.6; p less than 0.001). Additional research is needed to determine if this cytogenetic finding is due to a chromosome deletion, inversion, or polymorphism.
Dual-mobility constructs have gained popularity to mitigate dislocations after high-risk primary and revision total hip arthroplasties. Contemporary data have indicated that malseating of modular ...dual-mobility liners occurs in up to 6% of cases. The purpose of this cadaveric-based radiographic study was to determine the ability to accurately determine if modular dual-mobility liners were seated.
There were 10 hips (5 cadaveric pelvic specimens) used to implant modular dual-mobility liners of 2 designs. One had a liner that seated flush and the other had an extended rim. There were 20 constructs that were well-seated and 20 constructs were intentionally malseated. A comprehensive series of radiographs was reviewed by 2 blinded surgeons. Statistical analyses included Chi-squared testing, logistic regressions, and kappa statistics.
Radiographic assessment of liner malseating was not accurate with an elevated rim design with misdiagnosis in 40% (16 of 40). The flush design had diagnostic errors in 5% (2 of 40; P = .0002). Logistic regressions demonstrated a significantly higher risk of misdiagnosing a malseated liner in the elevated rim group (odds ratio 13). There were 12 of 16 misdiagnoses in the elevated rim group failing to recognize a malseated liner. Each surgeon had almost perfect agreement for intraobserver reliability for flush designs (k 0.90) and fair agreement in the elevated rim design (k 0.35).
A comprehensive series of plain radiographs can reliably detect a malseated modular dual-mobility liner with a flush rim design in 95% of cases. However, elevated rim designs are more difficult to accurately identify malseating on plain radiographs.
Emphysema in chronic obstructive pulmonary disease (COPD) can be characterized by high-resolution chest computed tomography (HRCT); however, the repeated use of HRCT is limited because of concerns ...regarding radiation exposure and cost.
To evaluate biomarkers associated with emphysema and COPD-related clinical characteristics, and to assess the relationships of soluble receptor for advanced glycation endproducts (sRAGE), a candidate systemic biomarker identified in this study, with single-nucleotide polymorphisms (SNPs) in the gene coding for RAGE (AGER locus) and with clinical characteristics.
Circulating levels of 111 biomarkers were analyzed for association with clinical characteristics in 410 patients with COPD enrolled in the TESRA study. sRAGE was also measured in the ECLIPSE cohort in 1,847 patients with COPD, 298 smokers and 204 nonsmokers. The association between 21 SNPs in the AGER locus with sRAGE levels and clinical characteristics was also investigated.
sRAGE was identified as a biomarker of diffusing capacity of carbon monoxide and lung density in the TESRA cohort. In the ECLIPSE cohort, lower sRAGE levels were associated with increased emphysema, increased Global Initiative for Chronic Obstructive Lung Disease stage, and COPD disease status. The associations with emphysema in both cohorts remained significant after covariate adjustment (P < 0.0001). One SNP in the AGER locus, rs2070600, was associated with circulating sRAGE levels both in TESRA (P = 0.0014) and ECLIPSE (7.07 × 10(-16)), which exceeded genome-wide significance threshold. Another SNP (rs2071288) was also associated with sRAGE levels (P = 0.01) and diffusing capacity of carbon monoxide (P = 0.01) in the TESRA study.
Lower circulating sRAGE levels are associated with emphysema severity and genetic polymorphisms in the AGER locus are associated with systemic sRAGE levels. Clinical trial registered with www.clinicaltrials.gov (NCT 00413205 and NCT 00292552).
Extracorporeal shock wave therapy (ESWT) has been shown to induce different biological effects on a variety of cells, including regulation and stimulation of their function and metabolism. ESWT can ...promote different biological responses such as proliferation, migration, and regenerations of cells. Recent studies have shown that mesenchymal stromal cells (MSCs) secrete factors that enhance the regeneration of tissues, stimulate proliferation and differentiation of cells, and decrease inflammatory and immune reactions. Clinically, the combination of these two therapies has been used as a treatment for tendon and ligament lesions in horses; however, there is no scientific evidence supporting this combination of therapies
. Therefore, the objectives of the study were to evaluate the effects of ESWT on equine umbilical cord blood mesenchymal stromal cells (CB-MSCs) proliferative, metabolic, migrative, differentiation, and immunomodulatory properties
equine CB-MSC cultures from independent donors were treated using an electrohydraulic shock wave generator attached to a water bath. All experiments were performed as triplicates. Proliferation, viability, migration and immunomodulatory properties of the cells were evaluated. Equine CB-MSCs were induced to evaluate their trilineage differentiation potential. ESWT treated cells had increased metabolic activity, showed positive adipogenic, osteogenic, and chondrogenic differentiation, and showed higher potential for differentiation toward the adipogenic and osteogenic cell fates. ESWT treated cells showed similar immunomodulatory properties to none-ESWT treated cells. Equine CB-MSCs are responsive to ESWT treatment and showed increased metabolic, adipogenic and osteogenic activity, but unaltered immunosuppressive properties.
studies are warranted to determine if synergistic effects occur in the treatment of musculoskeletal injuries if ESWT and equine CB-MSC therapies are combined.
Background Previous research has shown that smokers have reduced brain and platelet monoamine oxidase B (MAOB) activity. This is probably due to some components of tobacco smoke. When smokers quit, ...MAOB activity returns to normal. Reduced MAO activity may increase nicotine's addictive potential.
Aims To assess whether lazabemide, a reversible selective MAOB inhibitor, promotes smoking cessation.
Study design Double‐blind, randomized, placebo‐controlled, multicenter phase II study. Placebo, lazabemide 100 mg/day and 200 mg/day were administered for 8 weeks. This was a dose finding, proof‐of‐concept, exploratory study.
Setting General practices and anti‐smoking clinics in France and Belgium.
Participants Smokers smoking ≥15 cigarettes per day and motivated to quit.
Main outcome measure Sustained abstinence during the last 4 weeks of the study.
Findings The study was discontinued prematurely by the sponsor before randomization of the planned 420 smokers because of liver toxicity observed in other indications. Data of 330 randomized subjects could be analysed. Sustained abstinence during the last 4 weeks of treatment was 9%, 11% and 17% in the intent‐to‐treat population P for trend: 0.036 (one‐sided); 11%, 14% and 21% in the intent‐to‐treat population of smokers without those excluded because of discontinuation of the study n = 262, P for trend: 0.02 (one‐sided), and 19%, 27% and 35% in completers P for trend: 0.03 (one‐sided), in the placebo, lazabemide 100 mg/day and lazabemide 200 mg/day groups, respectively. Point prevalence abstinence (intent‐to‐treat population) at the end of treatment (week 8) was 17%, 19% and 30% in the placebo, lazabemide 100 mg/day and lazabemide 200 mg/day groups, respectively (placebo vs. lazabemide 200 mg/day: P = 0.01, one‐sided). No treatment emergent major adverse event occurred. More nausea and insomnia were reported with lazabemide than with placebo.
Conclusions MAOB inhibitors are promising treatments as an aid in smoking cessation. There may be an interest to develop MAOB inhibitors with an acceptable toxicity profile. Further studies may associate MAOB inhibitors with nicotine replacement therapies to increase therapeutic efficacy.
The aim of this study is to compare the effects of traditional nonsteroidal anti-inflammatory drugs with nonsteroidal anti-inflammatory drugs that are selective cyclooxygenase-2 (COX-2) inhibitors in ...the process of bone regeneration in a rat model.
Forty-four Wistar strain rats were subjected to osteotomy of the right femur and randomly divided into 3 groups according to the drug to be given (diclofenac, rofecoxib, or placebo). Each group was divided into 2 subgroups according to the time to euthanasia after the surgery. The animals of Subgroup 1 were submitted to euthanasia 2 weeks after surgery, and those of Subgroup 2, underwent euthanasia 4 weeks after surgery. Radiographic examinations and bone callus histomorphometry were analyzed.
No intergroup statistical difference was found in the bone callus area or in bone formation area 2 and 4 weeks after surgery. Intra-group analysis concerning the bone neoformation area inside the callus showed a significant difference within the diclofenac group, which presented less tissue.
Fracture consolidation in Wistar rats occurs within less than 2 weeks, and the use of nonsteroidal anti-inflammatory drugs does not significantly influence this process.
Comparar os efeitos do uso de antiinflamatórios não-esteróides tradicionais (AINES) e AINES que são inibidores seletivos da ciclooxigenase-2 (COX-2), no processo de regeneração óssea em ratos.
Quarenta e quatro ratos da linhagem Wistar submetidos a osteotomia do femur direito e divididos em três grupos, conforme o medicamento que receberam (diclofenaco, rofecoxib e placebo). Cada grupo foi dividido em dois subgrupos, conforme o tempo até o sacrifício, após a cirurgia. Os animais do subgrupo 1 foram sacrificados duas semanas após a cirurgia e os do subgrupo 2, quatro semanas após a cirurgia. Foram analisados exames radiográficos e a histomorfometria do calo ósseo.
Não foram encontradas diferenças estatísticas na área do calo ósseo 2 e 4 semanas após a cirurgia. No que se refere à área de neoformação óssea dentro do calo, observou-se diferença estatisticamente significante apenas dentro do grupo do diclofenaco, que apresentou menos tecido.
A consolidação da fratura em ratos Wistar ocorre dentro de 2 semanas e o uso de antiinflamatórios não-esteróides não influi de forma significante neste processo.
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