Vasorelaxant effect of the Lippia alba essential oil and its major constituent, citral, on the contractility of isolated rat aorta.

The Lippia alba (Mill.) N.E. Brown (Verbenaceae) species popularly known as lemon balm has sedative, analgesic and spasmolytic properties. This study aimed to evaluate the vasorelaxant effect of the L. alba essential oil (EOLa) and its major constituent, citral, rat on aorta. Isometric muscle contraction were induced by potassium (K 60 mM) or phenylephrine (PHE, 0.1 µM) in isolated aortic rings. EOLa and citral promoted a smooth muscle relaxant action, which was potentiated by the presence of the endothelium; PHE-induced contractions (0.1 µM) in aorta with endothelium, had EC50 values of 352.73 ± 19.39 µg/mL and 99.34 ± 7.2 µg/mL for EOLa and citral, respectively. In the presence of a nitric oxide synthase inhibitor, L-NAME, the EC50 values were 654.19 ± 10.46 µg/mL and 601.66 ± 10.922 µg/mL for EOLa and citral, respectively. EOLa and citral dose-dependently relaxed contractions induced by BAY-K 8644, a calcium channel agonist, and by Phorbol 12,13-dibutyrate an activator of protein kinase C. EOLa and citral produced a vasorelaxant effect in isolated aorta which was potentiated by the presence of endothelium. In summary, EOLa and citral, probably using several mechanisms of action, relaxed aortic smooth muscle with maximal pharmacologic efficacy.

Reduced bone mass and preserved marrow adipose tissue in patients with inflammatory bowel diseases in long-term remission.

Bone marrow adipose tissue has not been studied in patients with inactive inflammatory bowel disease. We found that these patients have preserved marrow adiposity even with low bone mass. Factors involved in bone loss in active disease may have long-lasting effects but do not seem to affect bone marrow adiposity. INTRODUCTION: Reduced bone mass is known to occur at varying prevalence in patients with inflammatory bowel diseases (IBD) because of inflammation, malnutrition, and steroid therapy. Osteoporosis may develop in these patients as the result of an imbalanced relationship between osteoblasts and adipocytes in bone marrow. This study aimed to evaluate for the first time bone mass and bone marrow adipose tissue (BMAT) in a particular subgroup of IBD patients characterized by long-term, steroid-free remission. METHODS: Patients with Crohn's disease (CD; N = 21) and ulcerative colitis (UC; N = 15) and controls (C; N = 65) underwent dual X-ray energy absorptiometry and nuclear magnetic resonance spectroscopy of the L3 lumbar vertebra for BMAT assessment. RESULTS: Both the CD and UC subgroups showed significantly higher proportions of patients than controls with Z-score ≤-2.0 at L1-L4 (C 1.54%; CD 19.05%; UC 20%; p = 0.02), but not at other sites. The proportions of CD patients with a T-score ˂-1.0 at the femoral neck (C 18.46%; CD 47.62%; p = 0.02) and total hip (C 16.92%; CD 42.86%; p = 0.03) were significantly higher than among controls. There were no statistically significant differences between IBD patients and controls regarding BMAT at L3 (C 28.62 ± 8.15%; CD 29.81 ± 6.90%; UC 27.35 ± 9.80%; p = 0.67). CONCLUSIONS: IBD patients in long-term, steroid-free remission may have a low bone mass in spite of preserved BMAT. These findings confirm the heterogeneity of bone disorders in IBD and may indicate that factors involved in bone loss in active disease may have long-lasting effects on these patients.

Probing the SERCA1a sarcoplasmic reticulum Ca2+-ATPase phosphorylation-site mutant D351E with inorganic phosphate

The expression of sarcoplasmic reticulum SERCA1a Ca2+-ATPase wild-type and D351E mutants was optimized in yeast under the control of a galactose promoter. Fully active wild-type enzyme was recovered in yeast microsomal membrane fractions in sufficient amounts to permit a rapid and practical assay of ATP hydrolysis and phosphoenzyme formation from ATP or Pi. Mutant and wild-type Ca2+-ATPase were assayed for phosphorylation by Pi under conditions that are known to facilitate this reaction in the wild-type enzyme, including pH 6.0 or 7.0 at 25°C in the presence of dimethylsulfoxide. Although glutamyl (E) and aspartyl (D) residue side chains differ by only one methylene group, no phosphoenzyme could be detected in the D351E mutant, even upon the addition of 40 percent dimethylsulfoxide and 1 mM 32Pi in the presence of 10 mM EGTA and 5 mM MgCl2. These results show that in the D351E mutant, increasing hydrophobicity of the site with inorganic solvent was not a sufficient factor for the required abstraction of water in the reaction of E351 with Pi to form a glutamylphosphate (P-E351) phosphoenzyme moiety. Mutation D351E may disrupt the proposed alignment of the reactive water molecule with the aspartylphosphate (P-D351) moiety in the phosphorylation site, which may be an essential alignment both in the forward reaction (hydrolysis of aspartylphosphate) and in the reverse reaction (abstraction of water upon formation of an aspartylphosphate intermediate).

Probing the SERCA1a sarcoplasmic reticulum Ca2+-ATPase phosphorylation-site mutant D351E with inorganic phosphate.

The expression of sarcoplasmic reticulum SERCA1a Ca2+-ATPase wild-type and D351E mutants was optimized in yeast under the control of a galactose promoter. Fully active wild-type enzyme was recovered in yeast microsomal membrane fractions in sufficient amounts to permit a rapid and practical assay of ATP hydrolysis and phosphoenzyme formation from ATP or Pi. Mutant and wild-type Ca2+-ATPase were assayed for phosphorylation by Pi under conditions that are known to facilitate this reaction in the wild-type enzyme, including pH 6.0 or 7.0 at 25 degrees C in the presence of dimethylsulfoxide. Although glutamyl (E) and aspartyl (D) residue side chains differ by only one methylene group, no phosphoenzyme could be detected in the D351E mutant, even upon the addition of 40% dimethylsulfoxide and 1 mM 32Pi in the presence of 10 mM EGTA and 5 mM MgCl2. These results show that in the D351E mutant, increasing hydrophobicity of the site with inorganic solvent was not a sufficient factor for the required abstraction of water in the reaction of E351 with Pi to form a glutamylphosphate (P-E351) phosphoenzyme moiety. Mutation D351E may disrupt the proposed alignment of the reactive water molecule with the aspartylphosphate (P-D351) moiety in the phosphorylation site, which may be an essential alignment both in the forward reaction (hydrolysis of aspartylphosphate) and in the reverse reaction (abstraction of water upon formation of an aspartylphosphate intermediate).

Phenotype analysis of lymphocytes of workers with chronic benzene poisoning.

Lifetime exposure to benzene is associated to a variety of blood disorders, and except for the risk of cancer, almost nothing is known concerning health impairment in individuals who are no longer exposed. In Brazil, this exposure is one of the serious problems in workplaces, and many workers have been laid off their jobs due to this intoxication, particularly in the State of Bahia, the largest producer of benzene in Latin America, which is the area of this study. From a larger study to describe health effects and genetic polymorphisms among workers with chronic benzene poisoning (CBP), this previous specific investigation analyzes the association between CBP and the pattern of sub-populations of lymphocytes. The study was performed with a CBP group (n=24) and a control group with other occupational diseases (n=24); both were selected at the Workers Health Study Center in the State of Bahia, Brazil. Clinical and epidemiologic variables were collected from medical records and from a detailed questionnaire. The average age was similar in the two groups (51.1 and 50.7, respectively). Analyzing the mean proportions of the sub-populations of lymphocytes, statistically significant differences were found for T cytotoxic cells (TCD8) (27.9; 19.4; p=0.002) and T helper memory cell (CD4CD45RO) (31.2; 37.0; p=0.015), respectively, for the CBP group and control group. These results should be viewed with caution because of the small sample size, but they strengthen a previous impression that workers exposed to benzene have their immune system impaired, even in the long term, which may contribute to some disorders and carcinogenesis process. These workers must be strictly followed up in a medical surveillance program. Although this problem has been known for a long time, this is the first attempt to study these specific effects in Brazil.

In vitro immunomodulatory activity of ruthenium complexes.

OBJECTIVE AND DESIGN: We have explored the in vitro immunomodulatory effects of pure ruthenium red and a series of pyridine and imidazole substituted ruthenium complexes (RCs). MATERIAL: Human peripheral blood lymphocytes and purified T cells were used in these studies along with various cell lines. METHODS: Cells were treated with dilutions of RCs and assessed in various assays of immune function, cytotoxicity and cell cycle progression. RESULTS: RCs efficiently blocked T cell receptor (TCR)-mediated stimulation (IC(50)'s in the low nM range) of human peripheral blood lymphocytes (hPBL) by various agents, including tetanus toxoid, alloantigens, superantigens, and receptor-specific antibodies. RCs are not cytotoxic to T cells. Antiproliferative activity was also observed for B cells. Some non-lymphoid cell lines or primary cultures showed sensitivity to the RCs, but only at higher concentrations. The inhibitory effect on human T cells was assessed and demonstrated at the level of proliferation (DNA synthesis), IL-2 secretion, and IL-2 receptor (CD25) upregulation. RCs also inhibited IL-2-mediated proliferation of antigen-induced T-cell blasts and the IL-2-dependent T cell line Kit-225. Cell cycle analysis indicates that RCs inhibit the progression of activated T cells from G(0)/G(1) to S phase. CONCLUSIONS: Since the mechanism of T cell inhibition by RCs appears to be different than that of rapamycin (RAP) or cyclosporin A (CsA), they may provide a new tool to investigate intracellular signaling in T cells, and may present novel opportunities for immunosuppression

Synthesis and immunosuppressive activity of ruthenium complexes.

The syntheses and immunosuppressive activity of ruthenium complexes are described. One of the complexes (1a) was shown to be a potent inhibitor of human T-lymphocyte proliferation with an IC50 of 5 nM. The activity of these complexes compares favorably to the well known immunosuppressants Cyclosporin A and Rapamycin.

1H NMR, EPR, UV-Vis, and Electrochemical Studies of Imidazole Complexes of Ru(III). Crystal Structures of cis-[(Im)(2)(NH(3))(4)Ru(III)]Br(3) and [(1MeIm)(6)Ru(II)]Cl(2).2H(2)O.

Comparisons of the spectroscopic properties of a number of Ru(III) complexes of imidazole ligands provide methods of distinguishing between various types of bonding that can occur in proteins and nucleic acids. In particular, EPR and (1)H NMR parameters arising from the paramagnetism of Ru(III) should aid in determining binding sites of Ru(III) drugs in macromolecules. Electrochemical studies on several imidazole complexes of ruthenium suggest that imidazole may serve as a significant pi-acceptor ligand in the presence of anionic ligands. Crystal structures are reported on two active immunosuppressant complexes. cis-[(Im)(2)(NH(3))(4)Ru(III)]Br(3) crystallizes in the triclinic space group P&onemacr; (No. 2) with the cell parameters a = 8.961(2) Å, b = 12.677(3) Å, c = 7.630(2) Å, alpha = 98.03(2) degrees, beta = 100.68(2) degrees, gamma = 81.59(2) degrees, and Z = 2 (R = 0.044). [(1MeIm)(6)Ru(II)]Cl(2).2H(2)O crystallizes in the monoclinic space group P2(1)/n (No. 14) with the cell parameters a = 7.994(2) Å, b = 13.173(4) Å, c = 14.904(2) Å, beta = 97.89(1) degrees, and Z = 2 (R = 0.052). The average Ru(II)-N bond distance is 2.106(8) Å.

Aneurisma da arteria esplenica. / Aneurysm of splenic artery

Apresentam os autores a experiencia de dois casos de aneurismas de arteria esplenica agudos no servico de cirurgia do HECC. Fazem revisao da literatura enfatizando o exame fisico e radiologico simples do abdomen dados fundamentais para o diagnostico em que o sinal do "anel de sinete" devera ser sempre pesquisado. Referem ainda os magnificos resultados obtidos com a aneurismectomia e esplenectomia

Parametros hematologicos normais em Fortaleza, Ceara. 1. Serie vermelha. / Normal hematological parameters in Fortaleza, Ceara. 1. Red blood cells

Determina os parametros hematologicos: hemacias, hemoglobulina, hematocrito, indices hematimetricos, reticulocitos e hemossedimentacao, em 200 individuos adultos normais, residentes em Fortaleza, Ceara.Os valores encontrados foram submetidos a analise estatisca e os resultados comparados com os da literatura