Changes in the production of monokines and prostaglandin E2 by the peripheral blood monocytes in patients with different clinico-immunological variants of rheumatoid arthritis]

As many as 39 patients aged 16-70 years with rheumatoid arthritis (RA) lasting 3 months to 20 years were examined. The diagnostic titers of rheumatoid factor were discovered in 23 patients. The control group was made up of 26 healthy subjects (donors). The activity of IL-1 in supernatants of peripheral blood monocytes (PBM) was measured by bioassay resting on co-stimulation of mouse thymocytes; quantitative determination of tumor necrosis factor-alpha (TNF-alpha) was made by ELISA, PGE2 was determined by RIA. As compared to the controls, the RA patients manifested an increase of the production of IL-1 beta, TNF-alpha and PGE2 of PBM, which rose with the disease activity. The RA patients demonstrated direct correlations between the level of IL-1 beta, TNF-alpha and PGE2 in supernatants of PBM, whereas the donors showed up a negative correlation between IL-1 beta activity and PGE2.     

The effects of exercise training associated with low-level laser therapy on biomarkers of adipose tissue transdifferentiation in obese women

Investigations suggest the benefits of low-level laser therapy (LLLT) to improve noninvasive body contouring treatments, inflammation, insulin resistance and to reduce body fat. However, the mechanism for such potential effects in association with exercise training (ET) and possible implications in browning adiposity processes remains unclear. Forty-nine obese women were involved, aged between 20 and 40 years with a body mass index (BMI) of 30–40 kg/m². The volunteers were divided into Phototherapy (808 nm) and SHAM groups. Interventions consisted of exercise training and phototherapy applications post exercise for 4 months, with three sessions/week. Body composition, lipid profile, insulin resistance, atrial natriuretic peptide (ANP), WNT5 signaling, interleukin-6 (IL-6), and fibroblast growth factor-21 (FGF-21) were measured. Improvements in body mass, BMI, body fat mass, lean mass, visceral fat, waist circumference, insulin, HOMA-IR, total cholesterol, LDL-cholesterol, triglycerides, and ANP in both groups were demonstrated. Only the Phototherapy group showed a reduction in interleukin-6 and an increase in WNT5 signaling. In addition, it was possible to observe a higher magnitude change for the fat mass, insulin, HOMA-IR, and FGF-21 variables in the Phototherapy group. In the present investigation, it was demonstrated that exercise training associated with LLLT promotes an improvement in body composition and inflammatory processes as previously demonstrated. The Phototherapy group especially presented positive modifications of WNT5 signaling, FGF-21, and ANP, possible biomarkers associated with browning adiposity processes. This suggests that this kind of intervention promotes results applicable in clinical practice to control obesity and related comorbidities.     

Molecular genetic analysis of BAX and cyclin D1 genes in patients with malignant glioma

INTRODUCTION AND OBJECTIVES: Brain tumorigenesis is a complex process involving multiple genetic alterations. Cyclin D1 and BAX genes are two of the most important regulators in controlling the normal proliferation and apoptosis of cells, respectively. In this study, we analysed the possibilities of involvement of cyclin D1 and BAX genes in the gliomagenesis. METHODS AND RESULTS: In determining gene alterations of exon 4 of cyclin D1 gene and exon 6 of BAX gene, all samples were amplified by polymerase chain reaction (PCR) and subsequently by direct sequencing. Our results showed a frameshift mutation (G base deletion) at nucleotide 82 of codon 28 in exon 4 of the cyclin D1 gene and another frameshift mutation with a deletion of C base at nucleotide 153 of exon 6 of the BAX gene in two separate cases of a glioblastoma multiform (WHO Grade IV) sample. CONCLUSION: These findings suggest that both cyclin D1 and BAX genes alteration are rarely found in brain tumors. However, the alteration might cause a significant effect of the normal protein production and this might contribute to the development of brain tumorigenesis in Malaysian patients.     

Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling

Although patients with advanced refractory solid tumors have poor prognosis, the clinical development of targeted protein kinase inhibitors offers hope for the future treatment of many cancers. In vivo and in vitro studies have shown that the oral multikinase inhibitor, sorafenib, inhibits tumor growth and disrupts tumor microvasculature through antiproliferative, antiangiogenic, and/or proapoptotic effects. Sorafenib has shown antitumor activity in phase II/III trials involving patients with advanced renal cell carcinoma and hepatocellular carcinoma. The multiple molecular targets of sorafenib (the serine/threonine kinase Raf and receptor tyrosine kinases) may explain its broad preclinical and clinical activity. This review highlights the antitumor activity of sorafenib across a variety of tumor types, including renal cell, hepatocellular, breast, and colorectal carcinomas in the preclinical setting. In particular, preclinical evidence that supports the different mechanisms of action of sorafenib is discussed.     

Vasopressin and epinephrine in the treatment of cardiac arrest: an experimental study

Background

Epinephrine remains the drug of choice for cardiopulmonary resuscitation. The aim of the present study is to assess whether the combination of vasopressin and epinephrine, given their different mechanisms of action, provides better results than epinephrine alone in cardiopulmonary resuscitation.

Methods

Ventricular fibrillation was induced in 22 Landrace/Large-White piglets, which were left untreated for 8 minutes before attempted resuscitation with precordial compression, mechanical ventilation and electrical defibrillation. Animals were randomized into 2 groups during cardiopulmonary resuscitation: 11 animals who received saline as placebo (20 ml dilution, bolus) + epinephrine (0.02 mg/kg) (Epi group); and 11 animals who received vasopressin (0.4 IU/kg/20 ml dilution, bolus) + epinephrine (0.02 mg/kg) (Vaso-Epi group). Electrical defibrillation was attempted after 10 minutes of ventricular fibrillation.

Results

Ten of 11 animals in the Vaso-Epi group restored spontaneous circulation in comparison to only 4 of 11 in the Epi group (p = 0.02). Aortic diastolic pressure, as well as, coronary perfusion pressure were significantly increased (p < 0.05) during cardiopulmonary resuscitation in the Vaso-Epi group.

Conclusion

The administration of vasopressin in combination with epinephrine during cardiopulmonary resuscitation results in a drastic improvement in the hemodynamic parameters necessary for the return of spontaneous circulation.     

Atenolol in combination with epinephrine improves the initial outcome of cardiopulmonary resuscitation in a swine model of ventricular fibrillation

Study Objectives

The aim of the present study was to assess whether a β-adrenergic blocking agent such as atenolol, administered during cardiopulmonary resuscitation, would improve initial resuscitation success.

Methods

Ventricular fibrillation was induced in 20 Landrace/Large White piglets, which were left untreated for 8 minutes before attempted resuscitation with precordial compression, mechanical ventilation, and electrical defibrillation. Animals were randomized into 2 groups (10 animals each) to receive saline as placebo (20 mL dilution, bolus) + epinephrine (0.02 mg/kg) (group A) or atenolol (0.05 mg/kg per 20 mL dilution, bolus) + epinephrine (0.02 mg/kg) (group B) during cardiopulmonary resuscitation. Electrical defibrillation was attempted after 10 minutes of ventricular fibrillation.

Results

Nine animals in group B restored spontaneous circulation in comparison to only 4 in group A. Aortic systolic and diastolic pressures as well as coronary perfusion pressure were significantly increased during cardiopulmonary resuscitation in group B. Furthermore, postresuscitation heart rate of the atenolol-treated group was significantly decreased.

Conclusions

A β-adrenergic blocking agent, when administered during cardiopulmonary resuscitation, significantly improves initial resuscitation success and increases blood and coronary perfusion pressures during cardiopulmonary resuscitation.