Inflammatory process caused by intraperitoneal injection of polyester in the rat: chemotactic activity in lavage fluid from the cavity

Minced polyester threads introduced into peritoneal cavity of guinea pigs or rats cause a granulomatous inflammation with evidence of macrophage stimulation. Chemotactic agents play an important role in the inflammatory reaction; they may be exogenous and/or endogenous. These are released locally by the cells involved in inflammation. In this paper the chemotactic effects of the peritoneal fluids from rats bearing the polyester inflammatory process, have been studied on PMN cells "in vitro". The peritoneal cavity fluids were obtained by washing the cavity of untreated rats or rats intraperitoneally injected with polyester, 1, 3, 7, 14 days after the intraperitoneal injection. The chemotactic response was assayed by employing modified chemotaxis Boyden chambers (Blind Well Neuro Probe) and polymorphonuclear leukocytes from normal or treated rats. Quantification of the migration was calculated by chemotactic index (A/B) (B = random migration, A = chemotaxis). The results demonstrated that the peritoneal fluids taken 3 and 7 days after the intraperitoneal polyester injection, elicit an evident chemotaxis response greater than that showed by peritoneal fluids from control rats. It is suggested that chemotactic factors can be produced and released by mononuclear cells involved in the inflammatory process.     

Manganese Tetraphenylporphyrins Catalyzed Selective Oxidation of Purine Derivatives

Abstract

The oxidation of purine derivatives using porphyrins as catalysts and dimethyldioxirane (DMDO) as oxygen atom donor is reported. The regioselectivity of the oxidation was found to be dependent on the presence of a free OH moiety on the N(9)-side chain of the substrate and on the structure of the catalyst.     

Reduction in neuronal L-type calcium channel activity in a double knock-in mouse model of Alzheimer's disease

Increased function of neuronal L-type voltage-sensitive Ca^2 + channels (L-VSCCs) is strongly linked to impaired memory and altered hippocampal synaptic plasticity in aged rats. However, no studies have directly assessed L-VSCC function in any of the common mouse models of Alzheimer's disease where neurologic deficits are typically more robust. Here, we used cell-attached patch-clamp recording techniques to measure L-VSCC activity in CA1 pyramidal neurons of partially dissociated hippocampal “zipper” slices prepared from 14-month-old wild-type mice and memory-impaired APP/PS1 double knock-in mice. Surprisingly, the functional channel density of L-VSCCs was significantly reduced in the APP/PS1 group. No differences in voltage dependency and unitary conductance of L-VSCCs were observed. The results suggest that mechanisms for Ca^2 + dysregulation can differ substantially between animal models of normal aging and models of pathological aging.     

Melanoma and subcutaneous adipose tissue: Role of peritumoral adipokines in disease characterization and prognosis

In the last decades, the concept of adipose organ has emerged, giving adipose tissue an active endocrine and immunologic function through the secretion of multiple cytokines and chemokines that seem to be implicated in the development and progression of several cancer, including cutaneous melanoma. In this pilot experimental study, we analyzed the expression in the peritumor subcutaneous adipose tissue of the most significant adipokines involved in the processes of carcinogenesis and metastasis in a population of melanoma patients and in two control groups composed of melanocytic nevi and epidermoid cysts, respectively. We correlated the results obtained with the main disease prognostic factors observing a statistically significant increase in the expression of PAI1, LEP, CXCL1, NAMPT, and TNF-α at the level of the peritumor tissue of the melanoma samples compared to the control groups and a correlation of the same with the histopathological prognostic factor of melanoma. Our preliminary study shows that the overexpression of PAI1, LEP, CXCL1, NAMPT, and TNF-α may contribute to the growth and to the local aggressiveness of cutaneous melanoma. It opens the hypothesis of a direct oncogenic role of subcutaneous adipose tissue and adipokines in the tumorigenesis of melanoma.     

Inflammatory reaction to polyester material in the guinea pig. V. Semiautomatic determination of peritoneal cell volume

The volume of the peritoneal cells of guinea pigs treated with injections of 1) minced polyester threads (Mersilene), 2) saline, and of untreated animals, has been determined utilizing a Coulter Counter coupled with a pulse height analyzer. The volumetric test on the whole cell population has emphasized a distinctly bimodal distribution, due to the presence of two cellular types picked out as first peak (P 1 degrees) and second peak (P 2 degrees), while the non-adherent cells (CNA) have shown an unimodal distribution. Statistically significant difference in the mean volumes have been found between the P 1 degrees and P 2 degrees cells and between the CNA and P 1 degrees cells. The percentage of CNA in the whole cell population significantly decreases in "Mersilene"-treated guinea pigs.     

Effects of some indoor environmental factors on respiratory symptoms and lung function in a sample of young non smokers in North Italy

Summary We evaluated the effects of some indoor environmental factors in a non smoking subsample (n=381, age 8–19 years) of the general population living in the Po River Delta. Each subject completed an interviewer-administered standardized questionnaire on respiratory symptoms and risk factors. Acceptable maneuvers of forced vital capacity and slope of alveolar plateau of nitrogen were obtained in 96% and 59% of the subjects, respectively. In the houses there were more frequently natural gas for cooking (86%) than bottled gas (14%) and central heating (82%) than stove (18%). As regards passive smoking exposure, 18% of subjects had both parents smoking, 50% had one parent smoking. Significantly higher prevalence rates of wheeze, dyspnea, diagnosis of asthma were found in subjects of both sexes using bottled gas for cooking in comparison to those using natural gas, when also exposed to passive smoking. An insignificant trend towards higher symptom rates was shown by those using stove, instead of central heating. Lung function was affected only in females: those with both parents smoking had reduced forced expirograms, those with bottled gas for cooking or stove for heating had a decreased peak expiratory flow. Interactions of stove and passive smoking on peak expiratory flow and on slope of alveolar plateau were statistically significant. These findings confirm the mild adverse respiratory effects of certain home environment factors shown by other epidemiologic surveys in North Europe and in the USA. They have been a basis for the implementation, under the auspices of National Research Council and Electric Energy Authority, of future specific studies in which continuous monitoring of indoor pollutants and repeated recording of symptoms and lung function in North and Central Italy will be performed.     

Genetic structure of the human population in the Po delta

The genetic structure of the population of Ferrara Province in the Po delta in Italy was investigated using chi 2 analysis, kinship analysis, analysis of correspondences, and geographical mapping of principal components of gene frequencies. chi 2 Analysis tests for Hardy-Weinberg equilibrium and for heterogeneity of gene and phenotype frequencies; kinship analysis tests for association between indicators of genetic and geographic proximity; analysis of correspondences relates localities and genetic systems in an eigenvectorial space; and geographic mapping displays the principal components of gene frequencies in the real space. In 1,364 adults in 26 residential units, seven presumably neutral isoenzyme systems were typed; ACP1 ESD, GLO I, GPT, PGD, PGM1 and PGP. It was found that average kinship for these neutral systems is correlated with geographic distance in this small area, but not as strongly as kinship for beta-thalassemia. A north-south gradient was observed for ESD. Analysis of correspondences indicated GPT, PGM1, and GLO I as the systems contributing most to differentiation within the province. The maps obtained from principal components of gene frequencies were consistent with the migrational history of the area.     

Distinct modulation of voltage-gated and ligand-gated Ca2+ currents by PPAR-γ agonists in cultured hippocampal neurons

Type 2 diabetes mellitus is a metabolic disorder characterized by hyperglycemia and is especially prevalent in the elderly. Because aging is a risk factor for type 2 diabetes mellitus, and insulin resistance may contribute to the pathogenesis of Alzheimer's disease (AD), anti-diabetic agents (thiazolidinediones-TZDs) are being studied for the treatment of cognitive decline associated with AD. These agents normalize insulin sensitivity in the periphery and can improve cognition and verbal memory in AD patients. Based on evidence that Ca²⁺ dysregulation is a pathogenic factor of brain aging/AD, we tested the hypothesis that TZDs could impact Ca²⁺ signaling/homeostasis in neurons. We assessed the effects of pioglitazone and rosiglitazone (TZDs) on two major sources of Ca²⁺ influx in primary hippocampal cultured neurons, voltage-gated Ca²⁺ channel (VGCC) and the NMDA receptor (NMDAR). VGCC- and NMDAR-mediated Ca²⁺ currents were recorded using patch-clamp techniques, and Ca²⁺ intracellular levels were monitored with Ca²⁺ imaging techniques. Rosiglitazone, but not pioglitazone reduced VGCC currents. In contrast, NMDAR-mediated currents were significantly reduced by pioglitazone but not rosiglitazone. These results show that TZDs modulate Ca²⁺-dependent pathways in the brain and have different inhibitory profiles on two major Ca²⁺ sources, potentially conferring neuroprotection to an area of the brain that is particularly vulnerable to the effects of aging and/or AD.