Breast milk studies in the Bitterfeld district

Human milk samples were tested for pesticide residues (particularly chlorinated hydrocarbons) in 1996 in continuation of the environmental medical tests conducted in 1990 and 1993 in Bitterfeld county. Although the overall human milk contamination due to chlorinated hydrocarbons was reduced, there were still higher concentrations of DDT and beta-HCH detected compared to the concentrations found in what was formerly West Germany. The objective of this follow-up testing of 106 human milk samples was to observe overall trends as well as the specific effects of sanitary and environmental protection measures after three years. Sample preparation included fat extraction and chromatographic column studies. The extracts were analyzed by means of two different gas chromatography systems based on electron-catching detectors. Overall, the contamination was reduced compared to the years of 1990 and 1993. Contaminant concentrations did not exceed the "tolerable concentration" while using a safety factor of 10. However, few beta-HCH (2% of the samples), HCB (22%), total DDT (20%), and more than half of total PCB samples exceeded the "tolerable concentrations" while using a safety factor of 100. A major decrease in the average contamination was noticed for total PCB (63% decrease for 0.3 mg/kg of milk fat), beta-HCH (77% decrease for 0.056 mg/kg of milk fat), and HCB (57% decrease for 0.091 mg/kg of milk fat). The concentration of the heptachlorepoxide was even reduced to 1%. Whereas the DDT and DDD concentrations were also reduced compared to 1993 (83% decrease for 0.033 mg/kg of milk fat, and 84% decrease of 0.005 mg/kg of milk fat), the DDE concentration increased (32% increase for 0.755 mg/kg of milk fat). This can be explained by the decomposition of enzymes from DDT to DDE and the extremely high accumulation tendency of this metabolite. The results show that the contamination of women over time was influenced by two contrary factors. On one hand, the internal exposure increases with age; on the other hand lactation eliminates contaminants from the body of the mother. Comparison to other states' data shows that the results match the overall picture of the residue situation in Germany. Results of the environmental-medical investigations from 1996 demonstrate a predominant decrease of contamination with chlorinated hydrocarbons within the human body. This tendency was possibly influenced by two developments. The global usage of persistent chlorinated hydrocarbons was critically observed and regulated more strictly in recent years, which decreased their concentration tremendously. The other reason for the reduction of contamination by chlorinated hydrocarbons in the county of Bitterfeld could be the improving environmental situation in this region.     

Increased mucosal inflammatory cytokines in children with Helicobacter pylori-associated gastritis

The concentrations of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and IL-1-β in tissue homogenates of gastric mucosal biopsy specimens, and in gastric juice samples from Helicobacter pylori-positive and -negative children, were determined. The study population comprised 30 children with recurrent abdominal pain attending upper gastrointestinal endoscopy. Of these patients 18 were infected with H. pylori. Cytokine concentrations in gastric biopsy homogenate supernatants and in gastric juice were measured by enzyme-linked immunosorbent assay (ELISA). TNF-α levels in gastric juice and in gastric biopsy homogenate supernatants in patients with H. pylori-positive gastritis were found to be significantly higher than those in children without H. pylori infection. IL-6 levels were also higher in H. pylori -infected subjects, but the difference in IL-6 concentrations measured in gastric juice and biopsy homogenate supernatants did not reach statistical significance. IL-1-β concentrations in both specimens showed no significant difference between the two groups of children. It was suggested that increased levels of inflammatory cytokines, especially TNF-α and IL-6 generated locally within the gastric mucosa might be implicated in the pathogenesis of H. pylori-associated gastritis in childhood.     

Epidemiology of periodontal diseases in adults from Latin America

A decade has passed since we first reviewed the epidemiology of periodontal diseases in Latin America. At that time, lack of population‐based studies was the norm and our conclusions were based on very limited evidence. The aim of the present comprehensive review was to update and expand our previous work by providing a broad overview of Latin America and its current social, economic and demographic status and by focusing on the epidemiology of periodontal diseases in Latin American adults published in the last 15 years. The amount of periodontal epidemiological data available has increased but is still restricted to a few countries only. The scope of the literature available has also broadened to include oral health‐related quality of life and systemic interactions; however, most studies had methodological limitations that might have biased their results. In general, periodontitis was very prevalent, but severe periodontal destruction was localized. Besides being associated with well‐established risk factors, periodontitis was associated with demographics and socio‐economic factors in Latin American populations. To advance epidemiological knowledge, population‐based cross‐sectional and longitudinal studies, using appropriate methodologies, should be the future focus of the research agenda of researchers and public health planners in Latin American countries.     

Monoclonal antibodies reveal receptor specificity among G-protein-coupled receptor kinases.

Guanine nucleotide-binding regulatory protein (G protein)-coupled receptor kinases (GRKs) constitute a family of serine/threonine kinases that play a major role in the agonist-induced phosphorylation and desensitization of G-protein-coupled receptors. Herein we describe the generation of monoclonal antibodies (mAbs) that specifically react with GRK2 and GRK3 or with GRK4, GRK5, and GRK6. They are used in several different receptor systems to identify the kinases that are responsible for receptor phosphorylation and desensitization. The ability of these reagents to inhibit GRK- mediated receptor phosphorylation is demonstrated in permeabilized 293 cells that overexpress individual GRKs and the type 1A angiotensin II receptor. We also use this approach to identify the endogenous GRKs that are responsible for the agonist-induced phosphorylation of epitope-tagged beta2- adrenergic receptors (beta2ARs) overexpressed in rabbit ventricular myocytes that are infected with a recombinant adenovirus. In these myocytes, anti-GRK2/3 mAbs inhibit isoproterenol-induced receptor phosphorylation by 77%, while GRK4-6-specific mAbs have no effect. Consistent with the operation of a betaAR kinase-mediated mechanism, GRK2 is identified by immunoblot analysis as well as in a functional assay as the predominant GRK expressed in these cells. Microinjection of GRK2/3-specific mAbs into chicken sensory neurons, which have been shown to express a GRK3-like protein, abolishes desensitization of the alpha2AR-mediated calcium current inhibition. The intracellular inhibition of endogenous GRKs by mAbs represents a novel approach to the study of receptor specificities among GRKs that should be widely applicable to many G-protein-coupled receptors.     

Glatiramer acetate attenuates the pro‐migratory profile of adhesion molecules on various immune cell subsets in multiple sclerosis

An altered expression pattern of adhesion molecules (AM) on the surface of immune cells is a premise for their extravasation into the central nervous system (CNS) and the formation of acute brain lesions in multiple sclerosis (MS). We evaluated the impact of glatiramer acetate (GA) on cell‐bound and soluble AM in the peripheral blood of patients with relapsing–remitting MS (RRMS). Fifteen patients treated de novo with GA were studied on four occasions over a period of 12 months. Surface levels of intracellular cell adhesion molecule (ICAM)‐1, ICAM‐3, lymphocyte function‐associated antigen (LFA)‐1 and very late activation antigen (VLA)‐4 were assessed in T cells (CD3⁺CD8⁺, CD3⁺CD4⁺), B cells, natural killer (NK) cells, natural killer T cells (NK T) and monocytes by five‐colour flow cytometry. Soluble E‐selectin, ICAM‐1, ICAM‐3, platelet endothelial cell adhesion molecule (PECAM)‐1, P‐selectin and vascular cell adhesion molecule (VCAM)‐1 were determined with a fluorescent bead‐based immunoassay. The pro‐migratory pattern in RRMS was verified by comparison with healthy controls and was characterized by up‐regulation of LFA‐1 (CD3⁺CD4⁺ T cells, B cells), VLA‐4 (CD3⁺CD8⁺ T cells, NK cells), ICAM‐1 (B cells) and ICAM‐3 (NK cells). Effects of GA treatment were most pronounced after 6 months and included attenuated levels of LFA‐1 (CD3⁺CD4⁺) and VLA‐4 (CD3⁺CD4⁺, CD3⁺CD8⁺, NK, NK T, monocytes). Further effects included lowering of ICAM‐1 and ICAM‐3 levels in almost all immune cell subsets. Soluble AM levels in RRMS did not differ from healthy controls and remained unaltered after GA treatment. The deregulated pro‐migratory expression profile of cell‐bound AM is altered by GA treatment. While this alteration may contribute to the beneficial action of the drug, the protracted development and unselective changes indicate more secondary immune regulatory phenomena related to these effects.     

Effect of nonsurgical periodontal therapy on serum and gingival crevicular fluid cytokine levels during pregnancy and postpartum

Background and Objective: A low‐grade systemic inflammatory status originating from periodontal infection has been proposed to explain the association between periodontal disease and systemic conditions, including adverse obstetric outcomes. The aim of this study was to evaluate the effect of periodontal therapy during pregnancy on the gingival crevicular fluid and serum levels of six cytokines associated with periodontal disease and preterm birth. Material and Methods: A subsample of 60 women (18–35 years of age) up to 20 gestational weeks, previously enrolled in a larger randomized clinical trial, was recruited for the present study. Participants were randomly allocated to receive either comprehensive nonsurgical periodontal therapy before 24 gestational weeks (n = 30, test group) or only one appointment for supragingival calculus removal (n = 30, control group). Clinical data, and samples of blood and gingival crevicular fluid, were collected at baseline, at 26–28 gestational weeks and 30 d after delivery. The levels of interleukin (IL)‐1β, IL‐6, IL‐8, IL‐10, IL‐12p70 and tumor necrosis factor‐α were analyzed by flow cytometry. Results: After treatment, a major reduction in periodontal inflammation was observed in the test group, with bleeding on probing decreasing from 49.62% of sites to 11.66% of sites (p < 0.001). Periodontal therapy significantly reduced the levels of IL‐1β and IL‐8 in gingival crevicular fluid (p < 0.001). However, no significant effect of therapy was observed on serum cytokine levels. After delivery, the levels of IL‐1β in the gingival crevicular fluid of the test group were significantly lower than were those in the control group (p < 0.001), but there were no significant differences between test and control groups regarding serum cytokine levels. Conclusion: Although periodontal therapy during pregnancy successfully reduced periodontal inflammation and gingival crevicular fluid cytokine levels, it did not have a significant impact on serum biomarkers.