Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain

New insights into the biological properties of cyclooxygenase-2 (COX-2) and its response pathway challenge the hypothesis that COX-2 is simply pro-inflammatory and inhibition of COX-2 solely prevents the development of inflammation and ameliorates inflammatory pain. The present study performed a comprehensive analysis of gene/protein expression induced by a selective inhibitor of COX-2, rofecoxib, compared with a non-selective COX inhibitor, ibuprofen, and placebo in a clinical model of acute inflammatory pain (the surgical extraction of impacted third molars) using microarray analysis followed by quantitative RT-PCR verification and Western blotting. Inhibition of COX-2 modulated gene expression related to inflammation and pain, the arachidonic acid pathway, apoptosis/angiogenesis, cell adhesion and signal transduction. Compared to placebo, rofecoxib treatment increased the gene expression of ANXA3 (annexin 3), SOD2 (superoxide dismutase 2), SOCS3 (suppressor of cytokine signaling 3) and IL1RN (IL1 receptor antagonist) which are associated with inhibition of phospholipase A(2) and suppression of cytokine signaling cascades, respectively. Both rofecoxib and ibuprofen treatment increased the gene expression of the pro-inflammatory mediators, IL6 and CCL2 (chemokine C-C motif ligand 2), following tissue injury compared to the placebo treatment. These results indicate a complex role for COX-2 in the inflammatory cascade in addition to the well-characterized COX-dependent pathway, as multiple pathways are also involved in rofecoxib-induced anti-inflammatory and analgesic effects at the gene expression level. These findings may also suggest an alternative hypothesis for the adverse effects attributed to selective inhibition of COX-2.     

Aneurysma spurium mit sekundärer AV-Fistel nach Nierenteilresektion

The increasing number of partial nephrectomies is accompanied by a higher incidence of rare iatrogenic vascular malformation. In the present case, an aneurysm with secondary arteriovenous (AV) fistula that developed after partial nephrectomy with a complicated course is described. The fistula was diagnosed during the sonographic follow-up in an asymptomatic patient. Due to the high flow rate of the shunt, the aneurysm was treated using open surgery.     

3-Tesla-MRT von seltenen zystisch imponierenden Prostatakarzinomen

Magnetic resonance imaging of rare cystic prostate cancers using multiparametric MRI (mp-MRI, 3 Tesla) shows, especially in solid tumor masses, the criteria of ESUR-MR classification with a PI-RADS >3 (“probably malignant”). In association with additional morphological evidence of intracystic hemorrhage and evidence of villous tumor nodules and irregular septa on the cyst wall, further malignancy criteria are met. MRI complementary to TRUS may be useful for targeted biopsy in solid tumor areas.     

Evaluation of the policy of secondary prevention against rheumatic fever among Egyptian children

Objective

We evaluated the effectiveness of long acting penicillin (LAP) as a 2-weekly regimen in winter and a 3-weekly regimen in summer for prevention of streptococcal colonization and also studied the common complaints of patients during the period of compliance for LAP administration. We also attempted to determine the incidence of relapses or recurrence of rheumatic fever (RF) after the onset of first episode of RF.

Patients & methods

210 rheumatic patients with good compliance to LAP (for at least one year) were included in the study. Demographic, clinical information, patients'' complaints and echocardiographic data of rheumatic patients were collected both retrospectively and prospectively. Anti-streptolysin O titre (ASOT) and throat swab culture were done at the end of the study (on Day 14 in the 2-weekly regimen and on Day 21 in the 3-weekly regimen).

Results

The age of onset of rheumatic fever was mostly between 5 and 15 years and the youngest patient was 2 years old. Subclinical carditis (SCC) was present in 79 (37%) of all the patients in the study population. Only 7 patients (3.3%) had a relapse within 2 years of the acute episode of RF. At the end of the study, ASOT was found to be high only in 11 patients (5.2%) and throat swab cultures were found negative in all patients

Conclusion

LAP regimen is fairly effective in eradicating streptococcal colonization. The incidence of relapse of RF within 2 years of the acute episode of RF is relatively low.     

An exercise-based cardiac rehabilitation programme for AF patients in the NHS: a feasibility study

There is increasing evidence for the role of exercise-based cardiac rehabilitation in the management of patients with atrial fibrillation (AF). However, this intervention has not yet been widely adopted within the National Health Service (NHS).We performed a feasibility study on the utilisation of an established NHS cardiac rehabilitation programme in the management of AF, and examined the effects of this intervention on exercise capacity, weight, and psychological health. We then identified factors that might prevent patients from enrolling on our programme.Patients with symptomatic AF were invited to participate in an established six-week exercise-based cardiac rehabilitation programme, composed of physical activity and education sessions. At the start of the programme, patients were weighed and measured, performed the six-minute walk test (6MWT), completed the Generalised Anxiety Disorder Questionnaire (GAD-7), and the Patient Health Questionnaire (PHQ-9). Measurements were repeated on completion of the programme.Over two years, 77 patients were invited to join the programme. Twenty-two patients (28.5%) declined participation prior to initial assessment and 22 (28.5%) accepted and attended the initial assessment, but subsequently withdrew from the programme. In total, 33 patients completed the entire programme (63.9 ± 1.7 years, 58% female). On completion, patients covered longer distances during the 6MWT, had lower GAD-7 scores, and lower PHQ-9 scores, compared with their baseline results. Compared with patients that completed the entire programme, those who withdrew from the study had, at baseline, a significantly higher body mass index (BMI), covered a shorter distance during the 6MWT, and had higher PHQ-9 and GAD-7 scores.In conclusion, enrolling patients with AF into an NHS cardiac rehabilitation programme is feasible, with nearly half of those invited completing the programme. In this feasibility study, cardiac rehabilitation resulted in an improved 6MWT, and reduced anxiety and depression levels, in the short term. Severe obesity, higher anxiety and depression levels, and lower initial exercise capacity appear to be barriers to completing exercise-based cardiac rehabilitation. These results warrant further investigation in larger cohorts.Key words: atrial fibrillation, cardiac rehabilitation, National Health Service     

Comparative characteristics of endothelial-like cells derived from human adipose mesenchymal stem cells and umbilical cord blood-derived endothelial cells

Adult peripheral blood contains a limited number of endothelial progenitor cells that can be isolated for treatment of ischemic diseases. The adipose tissue became an interesting source of stem cells for regenerative medicine. This study aimed to investigate the phenotype of cells obtained by culturing adipose-derived mesenchymal stem cells (ad-MSCs) in the presence of endothelial growth supplements compared to endothelial cells obtained from umbilical cord blood (UCB). Passage 3 ad-MSCs and mononuclear layer from UCB were cultured in presence of endothelial growth media for 3 weeks followed by their characterization by flow cytometry and polymerase chain reaction. After culture in endothelial inductive media, ad-MSCs expressed endothelial genes and some endothelial marker proteins as CD31 and CD34, respectively. Adipose tissue could be a reliable source for easy obtaining, expanding and differentiating MSCs into endothelial-like cells for autologous cell-based therapy.     

Unraveling the microstructural and optoelectronic properties of solution-processed Pr-doped SrSnO3 perovskite oxide thin films

The inorganic stannous-based perovskite oxide SrSnO₃ has been utilized in various optoelectronic applications. Facilitating the synthesis process and engineering its properties, however, are still considered challenging due to several aspects. This paper reports on a thorough investigation of the influence of rare-earth (praseodymium) doping on the microstructural and optoelectronic properties of pure and Pr-doped SrSnO₃ perovskite oxide thin films synthesized by a two-step simple chemical solution deposition route. Structural analysis indicated the high quality of the obtained phase and the alteration generated from the insertion of impurities. Surface scanning illustrated the formation of homogenous and crack-free SrSnO₃ thin films with a nanorod morphology, with an augmentation in size as the dopant ratios increased. Optical properties analysis showed an enhancement in the samples optical absorption with wide-range bandgap tuning. First-principles calculations revealed the exchange interactions between the 3d–4f states and their impact on the electronic properties of the pristine material. Hall-effect measurements revealed an immense decrement in the resistivity of the films upon increment of doping ratios, passing from 7.3 × 10⁻² Ω cm for the undoped sample to 4.8 × 10⁻² Ω cm for 7% Pr content, while a reverse trend was observed on the carrier mobility, rising from 2.5 to 7.6 cm² V⁻¹ s⁻¹ for 7% Pr content. The results emphasized the efficiency of the simple synthesis route to produce high-quality samples. The current findings will contribute to paving the way towards expanding the utilization of simple and cost-effective chemical solution deposition methods for the fast and large area growth of stannous-based perovskite oxides for optoelectronic applications.

Unraveling the optical, electronic and electrical properties of high-quality nanorod morphology spray-coated Pr-doped SrSnO₃ perovskite oxide thin films.