Effects of crude hydroalcoholic extract of Syzygium cumini (L.) Skeels leaves and continuous aerobic training in rats with diabetes induced by a high-fat diet and low doses of streptozotocin.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Syzygium cumini (L.) or Skeels (Myrtaceae) are widely used in Brazilian folk medicine to treat diabetes. AIM OF THE STUDY: The present study evaluated the functional capacity, biochemical parameters, oxidative stress and DNA damage from eight weeks of intervention with a crude hydroalcoholic extract of S. cumini leaves (EBH) and continuous aerobic training (TAC) in diabetic (D) rats. MATERIALS AND METHODS: A hydroalcoholic (50%) extract was prepared by ultrasound and phytochemical parameters (total phenols, total tannins and myricetin content) were analyzed. Thirty-seven male Wistar rats were divided into five groups: normoglycemic controls (CONT), diabetic controls (D-CONT), diabetics treated with extract (D+EBH), trained diabetic (D+TAC) and diabetics treated with extract and trained (D+EBH+TAC). Functional capacity was assessed with a maximum exercise capacity test; biochemical parameters with enzymatic kits; oxidative stress by superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive substances (TBARS) and oxidized dichlorofluorescein (DCF), and the DNA damage by the comet assay. RESULTS: The D+TAC and D+EBH+TAC groups showed better functional capacity at the end of interventions. The D+EBH group showed glucose and triglyceride reduction, lowest DNA damage index in the blood, liver, kidney, heart, lung and gastrocnemius muscle, improved SOD levels in the liver, kidney and lung, improved CAT levels in the kidney and lower lipid peroxidation in all tissues studied, compared to the D-CONT group. The exercise (D+TAC) was effective in reducing triglycerides, improving SOD levels in the lung, reducing lipid peroxidation in all tissues studied and reducing the DCF oxidation in the kidney, in addition to protecting against DNA damage in the blood and heart. However, the additive effect of the intervention protocols when combined (EBH+TAC) was observed only in improving the gastrocnemius SOD levels. The phytochemical analyses showed a high content of phenols and the presence of myricetin glycosides. CONCLUSION: The findings in this study suggest a crude hydroalcoholic extract of S. cumini leaves has potential hypoglycemic, hypolipidemic and protective properties acting against oxidative stress and against DNA damage, probably due to its phenols and myricetin glycoside content and the antioxidant properties of these constituents. Moreover, exercise was suggested to have beneficial effects on diabetes, improving functional capacity, ameliorating blood triglyceride control and decreasing lipid peroxidation, but with no effects on ameliorating blood glucose levels. The association of intervention protocols presented an additive effect on the antioxidant SOD activity in the muscle cells of diabetic rats.

Association between metabolic syndrome and periodontal disease.

BACKGROUND: Metabolic syndrome has been suggested as a potential risk factor for periodontal disease. Data based on NHANES III, with 7431 subjects aged 20 years or older, were analysed to confirm the association between metabolic syndrome and periodontal disease, and identify which components of metabolic syndrome might play a role in this association. METHODS: Clinical criteria for metabolic syndrome included: (1) abdominal obesity; (2) increased triglycerides; (3) decreased HDL cholesterol; (4) hypertension or current use of hypertension medication; and (5) high fasting plasma glucose. Periodontal disease was evaluated by probing pocket depth (PPD) and was defined as mean PPD≥2.5 mm. RESULTS: Women with two or more metabolic components had significantly increased odds of having periodontal disease as compared to those with no component [(two components, OR=5.6 (95% CI: 2.2-14.4); three or more, OR=4.7 (2.0-11.2)]. Using the definition of metabolic syndrome as having three to five metabolic components (reference group with <3 components), the adjusted odds ratios were 1.0 (0.7-1.6) for men and 2.1 (1.2-3.7) for women. Abdominal obesity was the largest contributory factor in both genders. CONCLUSIONS: While the association between metabolic syndrome and periodontal disease was particularly significant for women, abdominal obesity appeared to be the contributing metabolic factor for both genders.

Overview of risk factors for periodontal disease and implications for diabetes and cardiovascular disease.

Recent studies have shown that there is a definite relationship between diseases of the oral cavity, especially periodontal infections, and systematic diseases. Periodontal disease may also produce systemic effects in the body, including an association with cardiovascular disease. This article discusses the risk factors for periodontal disease, the pathogenesis and risk factors for cardiovascular disease, the relationship between periodontal infection and cardiovascular disease, and the need for future studies to further define the relationship between periodontal disease and cardiovascular disease.

Analysis of antigenic structure and human immune response to outer membrane protein CD of Moraxella catarrhalis.

Moraxella catarrhalis is an important cause of otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). Outer membrane protein CD (OMP CD) is a 45-kDa protein which is a potential vaccine antigen to prevent infections caused by M. catarrhalis. Eight monoclonal antibodies were used to study the antigenic structure of the OMP CD molecule by assaying recombinant peptides corresponding to the sequence of the protein. This approach identified two surface-exposed epitopes, including one near the amino terminus (amino acids 25 to 44) and one in the central region of the molecule (amino acids 261 to 331). Assays with serum and sputum supernatants of adults with COPD revealed variable levels of antibodies to OMP CD among individuals. To determine which portions of the OMP CD molecule were recognized by human antibodies, three human serum samples were studied with six recombinant peptides which span the sequence of OMP CD. All three sera contained immunoglobulin G antibodies which recognized exclusively the peptide corresponding to amino acids 203 to 260 by immunoblot assay. Adsorption experiments with whole bacteria established that some of the human antibodies are directed at surface-exposed epitopes on OMP CD. We conclude that OMP CD is a highly conserved molecule which contains at least two separate epitopes which are exposed on the bacterial surface. While individual adults with COPD show variability in the immune response to OMP CD, a specific region of the OMP CD molecule (amino acids 203 to 260) is important as a target of the human immune response.

Flow cytometric analysis of in vitro proinflammatory cytokine secretion in peripheral blood from multiple sclerosis patients.

The cytokines, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-2 (IL-2) are important endogenous proinflammatory proteins and have been linked to disease activity in multiple sclerosis. In this study, we use flow cytometric methodology to compare the secretion of IFN-gamma, IL-2, and TNF-alpha from peripheral blood-derived T cells of multiple sclerosis patients to the secretion in healthy controls. The percentages of IFN-gamma, IL-2, and TNF-alpha secreting cells are not significantly different between multiple sclerosis patients and controls. However, the TNF-alpha secreting CD3 cell percentage is correlated with the IFN-gamma and IL-2 secreting CD3 cell percentages in multiple sclerosis patients. In the controls, only the TNF-alpha secreting CD3 cell percentage is correlated with IFN-gamma. These findings show that correlated secretion of cytokines occurs in multiple sclerosis and suggest that concerted intercytokine interactions may play an important role in the disease.

Influence of the level of dietary lipid intake and maximal exercise on the immune status in runners.

Chronic exercise and high fat diets are associated with immune suppression. This study compares cellular immune responses at rest and after maximal exercise in runners after eating diets comprised of 17% low fat (LF), 32% medium fat (MF), and 41% high fat (HF) (4 wk each). VO2max increased significantly from the 17% to 41% fat diet. The leukocyte cell counts were significantly increased after exercise. In men, significantly higher proliferative response to phytohemagglutinin (PHA) (P < 0.004) was observed with MF diet, while response to pokeweed mitogen (PWM) was significantly decreased by MF and HF diets. The number of CD8+ (suppressor) T cells was significantly higher in men and exercise increased it significantly, while CD4+ (helper) T cells were not affected. Natural killer cells number was significantly increased 2.5 fold by exercise and with increase in dietary fat. The production of IL-2 by peripheral blood mononuclear cells was significantly higher in men (P < 0.0001) and increasing dietary fat significantly increased IL-2 production (P < 0.001). In men, exercise decreased the level of the proinflammatory cytokines (IL-1, IL-6 and TNF-alpha), whereas in women, with the exception of MF diet for IL-6, exercise had no effect. This study indicates that short, intense bouts of exercise in runners training 40 miles.wk-1 have mixed effects on the immune system. A high percentage of fat intake (41%) did not have any deleterious effects on the immune system of the well-trained runners.

Murine NK cell allospecificity-1 is defined by inhibitory ligands.

Hemopoietic allografts of normal and neoplastic origin are subject to NK cell-mediated resistance in mice. Susceptibility to this resistance is controlled by MHC-linked genes in a recessive manner. Several distinct specificities could be postulated to explain the strain-dependent pattern of resistance. These presumptive specificities for recognition are H-2 haplotype dependent, but the correspondence is not one-to-one. For example, resistance of H-2d or H-2b/d host to H-2 b graft operationally defines specificity-1, establishing its link with haplotype H-2b. To examine the molecular basis of specificity-1, spontaneous Dd-loss mutant clones were isolated from H-2b/d and H-2d hemopoietic cell lines, i.e., 416B of (C57BL/6 x DBA/2)F1 (B6D2F1) origin and L1210 of DBA/2 origin, both of which lack specificity-1. The expression of specificity-1 in the mutant clones was examined in vivo and in vitro. The results indicate that Dd-loss clones of 416B and L1210 lines express specificity-1. These data suggest that murine NK cell allospecificity-1 is defined primarily by the absence of the Dd molecule or other class I molecules sharing the protective motifs; no H-2b-associated genes play a relevant role. This conclusion is consistent with the missing self hypothesis of NK cell reactivity, and is in agreement with the observation that lysis of B6 targets by B6D2F1 NK cells is mediated mostly by cells that express Ly-49A and/or Ly-49G2.

Allospecificities of B6D2F1 hybrid NK cell subsets defined by Ly-49A expression.

More than 90% of IL-2-activated plastic-adherent murine splenocytes (A-LAK4 cells) are NK1.1+ NK cells and both H-2b/b homozygous C57BL/6- and H-2b/d heterozygous (C57BL/6 x DBA/2)F1 (B6D2F1)-derived populations of such cells contain an Ly-49A+ subset. In B6D2F1 A-LAK cells, as well as in freshly isolated spleen cells of the same mice, Ly-49A+ cells represent approximately 10% of NK1.1+ cells. However, the level of Ly-49A expression in B6D2F1 NK cells is lower than in C57BL/6 (B6). The cytolytic activity of B6- and B6D2F1-derived A-LAK cells against normal target cells is specific, and is in agreement with the known patterns of natural resistance in vivo against Hh-1-mismatched bone marrow allografts. H-2b lymphoma cells transfected with the Dd gene, but not the Ld gene, no longer express the Hh-1b phenotype that is recognized by B6D2F1 A-LAK cells, raising the possibility that this selective effect of the Dd gene on Hh-1b phenotype is related to the known inability of Ly-49A+ A-LAK cells to kill Dd-expressing tumor target cells. Depletion of Ly-49A+ A-LAK cells by Ab and complement reduces the lytic capacity of B6D2F1 A-LAK cells against normal B6 target cells of the Hh-1b phenotype to one-third of the original level. Conversely, positively selected Ly-49A+ A-LAK cells are enriched for the same activity. The results, therefore, favor the view that the Hh-1 phenotype of the target cells may be defined largely by the effector cell's recognition of class I Ags on the target cell surface.

Antibodies directed to the chemotactic factor receptor detect differences between chemotactically normal and defective neutrophils from LJP patients.

Localized juvenile periodontitis (LJP) is a progressively destructive infection of the supporting tissues of the teeth, primarily affecting adolescents. In this disease, patients' polymorphonuclear leukocytes (PMN) exhibit decreased chemotaxis (CTX) and decreased binding of the chemotactic peptide N-formyl-l-methionyl-l-leucyl-l-phenyl-alanine (FMLP) to specific receptors on the PMN surface. Since the FMLP receptor is involved in the activation of the PMN, and its subsequent response to chemotactic stimuli, a decrease in the chemotactic peptide receptor, as seen in LJP patients, is suspected to be a predisposing factor for this disease. To define differences in the FMLP receptor between CTX defective LJP patients and CTX normal donors, a battery of monoclonal antibodies reactive against the FMLP receptor was prepared. The FMLP receptor was affinity-purified, and was found to be comprised of two components, one of 68 kDa, and the other of 94 kDa. Only the 68 kDa component specifically bound a radioiodinated FMLP analogue in a photoaffinity experiment. Seven monoclonal antibodies were selected on the basis of their reactivity with the 68 kDa receptor component, and of these, 5 showed reduced binding against PMN from CTX defective LJP donors when compared to their reactivity against PMN from CTX normal subjects. Two of the 7 anti-68 kDa antibodies reacted with PMN from both sets of subjects at a comparable extent. Furthermore, the presence of 20 nmol of FMLP inhibited the binding of 5 of the anti-receptor antibodies to whole PMN, including one that showed no difference in binding between CTX normal and defective PMN, and 4 of the 5 that did show such difference.(ABSTRACT TRUNCATED AT 250 WORDS)