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In chemical plant workers producing pesticides chronic bronchitis and disturbed pulmonary ventilation are frequent. The aim of the examination of the staff (sewage-treatment plant, waste combustion plant, waste storage, industrial water pumping station)--16 males aged 21-53 years--was to assess: 1. Connective tissue metabolism--serum concentration of type I and III procollagen propeptides, collagen I telopeptide, hydroxyproline, alpha1-AP and alpha2-M antiproteases, interstitial collagenase (MMP-1) activity, as well as urine hydroxyproline and desmosine. 2. Free radical damage--serum malonic dialdehyde (TBARS) and ceruloplasmin concentration, erythrocyte antioxidant enzymes activity (SOD, catalase, GPx, GR), and neutrophils myeloperoxidase reaction. 3. Humoral (serum IgG, A and M, C3 complement component and the circulating immune complexes) and cellular (percentage of CD3, CD4 and CD8 lymphocytes) immunity rates. As compared to controls the following changes were found: 1. decreased MMP-1 activity and increased alpha2-M serum concentration; 2. increased erythrocyte SOD and GPx activities; 3. decreased percentage of T lymphocytes (CD3), increased serum concentration of the C3 complement component and the circulating immune complexes. The results were compared with those in workers of the departments producing liquid pesticides, dust pesticides and chlorfenvinphose, the changes of the investigated parameters were found to be less expressed.

The biology of pathogen-associated molecular patterns (PAMPs) stimulating APCs to differentiate into a Th1-promoting phenotype has been well characterized. Conversely, not a single pathogen product that promotes a Th2 phenotype has been rigorously identified. Strong Th2 responses and dendritic cell 2 maturation are driven by helminth extracts, and carbohydrates have been shown to be responsible for much of this activity. In this study, we show that a helminth carbohydrate, lacto-N-fucopentaose III (LNFPIII) functions as an innate Th2 promoter via its action on murine dendritic cells, with the alpha1-3-linked fucose required for this activity. In contrast to Th1-type PAMPs, which activate extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinases, the Th2 PAMP LNFPIII preferentially activates extracellular signal-regulated kinase. Furthermore, the ability of LNFPIII to drive DC2 maturation is dependent on signaling via Toll-like receptor 4. These data support a new understanding of how APCs integrate signaling pathways to produce a Th1- or Th2-promoting phenotype.

The aim of this study was to evaluate the RBC deformability and oxidative stress parameters during acute pancreatitis. Healthy volunteers and patients with mild or severe acute pancreatitis were evaluated. There were no changes in erythrocyte's deformability in patients with mild acute pancreatitis. In severe acute pancreatitis loss of deformability of erythrocytes was observed. Serum lipofuscin level increased both in mild and severe form of the disease. The superoxide dismutase (SOD) activity was increased in erythrocytes from mild and severe form without systemic complications and was positively correlated with erythrocyte's deformability in a severe form of acute pancreatitis. Significant positive correlation between serum total antioxidant status and deformability of erythrocytes in healthy humans and negative correlation in mild pancreatitis were found.

Immunomodulatory oligosaccharides found on helminths also are found in human milk, and both helminths and milk have been shown to be immunosuppressive. We have been examining the immunomodulatory capabilities of two oligosaccharides expressed in milk and on helminth parasites, lacto-N-fucopentaose III and lacto-N-neotetraose (LNnT). In an attempt to dissect mechanisms that lead to Th2 polarization and immune suppression, we examined the early response in mice to the glycoconjugate LNnT-Dextran (LNnT-Dex). We found that injection of LNnT-Dex expanded a cell population, phenotypically defined as Gr1(+)/CD11b(+)/F4/80(+), as early as 2 h after injection. Examination of spontaneous cytokine production showed that this Gr1(+)/F4/80(+) population of cells spontaneously produced low levels of proinflammatory cytokines, but higher levels of IL-10 and TGF-beta ex vivo, compared to peritoneal cells from mice injected with Dex. Gr1(+) cells adoptively suppressed naive CD4(+) T cell proliferation in vitro in response to anti-CD3/CD28 Ab stimulation. Suppression of naive CD4(+) cells involved cell contact and was dependent on IFN-gamma and NO, with a discrete role played by IL-10. Coculture of naive CD4(+)T cells with Gr1(+) suppressor cells did not lead to CD4(+) T cell apoptosis, although it did imprint on naive CD4(+) T cells a response characterized by lower levels of IFN-gamma, coincident with increased IL-13 production. Our results suggest that both human milk and helminth parasites may share a ligand-specific mechanism involved in the generation of anti-inflammatory mediators that suppress Th1-type and inflammatory responses.

Lacto-N-fucopentaose III (LNFPIII) is found in human milk and on the Th2 driving helminth parasite Schistosoma mansoni. This pentasaccharide drives Th2-type responses in vivo and in vitro when conjugated to a carrier. In an attempt to further understand early events in Th1 to Th2 switching, we examined phenotypic and functional changes in peritoneal cell populations in BALB/c and SCID mice following LNFPIII-dextran injection. We found that i.p. injection with LNFPIII-dextran resulted in rapid (<20 h) expansion of the Gr1(+) subpopulation of F4/80(+)/CD11b(+) peritoneal cells, comprising up to 75% of F4/80(+)/CD11b(+) peritoneal cells compared with 18% in uninjected or dextran-injected mice. Functionally, these cells suppressed anti-CD3- and anti-CD28-induced proliferation of naive CD4(+) T cells. LNFPIII-dextran also expanded functional Gr1(+) suppressor macrophages in SCID mice, demonstrating that expansion and function of suppressor cells did not require T cells. Suppression in both BALB/c and SCID mice was NO and IFN-gamma dependent, as addition of inhibitors of inducible NO synthase (N(G)-monomethyl-L-arginine), as well as anti-IFN-gamma Abs, restored the ability of CD4(+) T cells to proliferate in vitro. Depletion of the F4/80(+) subset of Gr1(+) cells eliminated the suppressive activity of peritoneal exudate cells showing that these cells were macrophages. Thus, LNFPIII-dextran rapidly expands the Gr1(+) suppressor macrophage population in the peritoneal cavities of otherwise naive mice. These Gr1(+) cells suppress proliferation of naive CD4(+) T cells in an NO-dependent mechanism, and may play a regulatory role in the switching of Th1- to Th2-type responses.

Background: Water immersion stress (WIS) in rats causes decrease in deformability of red blood cells (RBC). We hypothesize that this phenomenon is mediated by reactive oxygen species. Since tirilazad mesylate (U74006F) is a potent scavenger of free oxygen radicals, the aim of this study was to investigate possible influence of this drug on WIS induced decrease in RBC deformability in rats., Material and Methods: The rats were injected i.p. with tirilazad mesylate in a dose of 10 mg per kg body weight or vehiculum at the beginning of the experiment and immersed in water at 23 degrees C to the depth of xyphoid for 5 h. Control rats were kept in normal environment. After 6 h blood samples were collected for examination. An elongation index of RBC measured by Rheodyn SSD (Myrenne GmbH, Germany) was used as a parameter of deformability. Lipid peroxidation products have been assayed in RBC by BIOXYTECH LPO-586 kit., Results: Tirilazad mesylate prevents a decrease in RBC deformability, but does not prevent an increase in concentration of lipid peroxidation products in erythrocytes during WIS., Conclusion: Positive effect of tirilazad on stress induced decrease in RBC deformability is not related to inhibition of lipid peroxidation within the erythrocytes.

In a country with a high cardiovascular mortality rate, lipid profiles were studied in 929 adolescents (440 from affected and 489 from non-affected families for cardiovascular disease and hypercholesterolaemia). In 334 children with elevated or borderline total cholesterol level, lipid profiles were re-measured after a 1-y period. In boys from affected families, in contrast to boys from non-affected families, significantly higher total cholesterol levels (4.36 +/- 0.81 vs 4.19 +/- 0.78 mmol/L, p < 0.05) and LDL-C level (2.1 +/- 0.72 vs 1.89 +/- 0.79 mmol/L, p < 0.05) and significantly lower HDL-cholesterol levels (1.81 +/- 0.34 vs 1.93 +/- 0.38 mmol/L, p < 0.05) were found. The odds ratio for being in the most unfavourable decile for LDL-cholesterol was significantly higher for girls from affected families (2.17, p = 0.02). A relatively high HDL-C level as well as a favourable TC/HDL-C ratio was demonstrated in all groups, being lowest in boys from affected families. A significant correlation was found between baseline lipids and their values re-measured after 1 y. It is concluded that (1) adolescents with a positive family history are at increased risk for unfavourable lipid profile, (2) adolescents with elevated total cholesterol and LDL-cholesterol levels remain hypercholesterolaemic after a 1-y period and are therefore candidates for further biochemical and clinical monitoring, and (3) children with elevated total cholesterol may not be at high risk for cardiovascular disease owing to the favourable TC/HDL-C ratio. The study results do not indicate that general cholesterol screening in Polish adolescents is necessary, as the proportion of children with elevated LDL-cholesterol is relatively low.

The glyoxalase system catalyses the conversion of methylglyoxal to D-lactate via intermediate S-D-lactoylgutathione. This system consists of two enzymes, glyoxalase I and glyoxalase II. A link between the development of diabetic complications and the glyoxalase system has been suggested at the genetic and metabolic level. Insulin-dependent diabetic patients without complications (retinopathy, neuropathy) had a significantly higher frequency of the glyoxalase phenotype GLO 1-1 than patients with complications. Periodic hyperglycaemia may contribute to the development of diabetic complication through methylglyoxal-mediated changes in protein solubility and aggregation characteristics.

The formation of methylglyoxal is increased during hyperglycemia associated with diabetes mellitus. Enhanced methylglyoxal concentration in biological systems is associated with increased reversible and irreversible modification of protein. The chronic exposure to high methylglyoxal concentrations appears to be linked to the development of diabetic complications. Intervention with aldose reductase inhibitors or aminoguanidine, which is an efficient scavenger of methylglyoxal, in diabetes mellitus may prevent increased methylglyoxal concentration.

The glyoxalase system catalyses the conversion of methylglyoxal (and other 2-ketoaldehydes) to D-lactic acid via the intermediate S-D-lactoylglutathione. It comprises two enzymes, glyoxalases I and glyoxalases II, and catalytic amount to reduced glutathione. Methylglyoxal inhibits cell growth, while the glyoxalase system by breaking down methylglyoxal may act as a promoter of cell growth. Inhibitors of glyoxalases may serve as possible therapeutic agents against cancer by virtue of their ability to elevate the level of methylglyoxal in the body.

Yohimbine, an alpha 2-receptor antagonist, was examined for its suitability in the treatment of obesity. Twenty female obese outpatients were subjected to a 3-week low-energy diet (1,000 kcal/day), after which they were randomly allocated according to a double-blind study protocol to two treatments: 10 subjects received 5 mg yohimbine per os 4 times a day and 10 received a placebo for 3 weeks, in addition to a low-energy diet of 1,000 kcal/day. Before inclusion in the study, as well as the end of each of the 3-week treatment periods, thermogenesis (resting and exercise energy expenditure) was assessed by indirect calorimetry; serum noradrenaline concentration was taken as an index of sympathetic system activity and serum glycerol level as an index of lipolysis. Yohimbine significantly increased the mean weight loss in patients on a low-energy diet: 3.55 +/- 0.24 kg (yohimbine) vs. 2.21 +/- 0.37 kg (placebo), P less than 0.005. With yohimbine, a steady level of effort-induced energy expenditure and sympathetic system activity was maintained. No significant effect of yohimbine on lipolysis was observed under the experimental conditions of this study. In another group of 15 obese inpatients (11 women and 4 men) the influence of 15 mg yohimbine per os vs. placebo on gastric emptying of a radiolabelled solid meal was examined in a double-blind manner with the use of a gamma camera. No significant effect of yohimbine on gastric emptying was revealed--the mean gastric transit time was 42.0 +/- 0.4 min after placebo and 41.8 +/- 0.5 min after yohimbine. The results obtained warrant further research on the applicability of alpha 2-receptor inhibitory drugs as a supplementary management in the treatment of obesity.