CaNa2EDTA chelation attenuates cell damage in workers exposed to lead--a pilot study.

Lead induced oxidative cellular damage and long-term persistence of associated adverse effects increases risk of late-onset diseases. CaNa2EDTA chelation is known to remove contaminating metals and to reduce free radical production. The objective was to investigate the impact of chelation therapy on modulation of lead induced cellular damage, restoration of altered enzyme activities and lipid homeostasis in peripheral blood of workers exposed to lead, by comparing the selected biomarkers obtained prior and after five-day CaNa2EDTA chelation intervention. The group of smelting factory workers diagnosed with lead intoxication and current lead exposure 5.8 ± 1.2 years were administered five-day CaNa2EDTA chelation. Elevated baseline activity of antioxidant enzymes Cu, Zn-SOD and CAT as well as depleted thiols and increased protein degradation products-carbonyl groups and nitrites, pointing to Pb induced oxidative damage, were restored toward normal values following the treatment. Lead showed inhibitor potency on both RBC AChE and BChE in exposed workers, and chelation re-established the activity of BChE, while RBC AChE remained unaffected. Also, genotoxic effect of lead detected in peripheral blood lymphocytes was significantly decreased after therapy, exhibiting 18.9% DNA damage reduction. Administration of chelation reversed the depressed activity of serum PON 1 and significantly decreased lipid peroxidation detected by the post-chelation reduction of MDA levels. Lactate dehydrogenase LDH1-5 isoenzymes levels showed evident but no significant trend of restoring toward normal control values following chelation. CaNa2EDTA chelation ameliorates the alterations linked with Pb mediated oxidative stress, indicating possible benefits in reducing health risks associated with increased oxidative damage in lead exposed populations.

Cytogenetic effects of 8-Cl-cAMP on human and animal chromosomes.

PURPOSE: To assess the cytogenetic effects in vitro and in vivo of a non-cytotoxic antitumor agent with biomodulator activity, 8-chloro-3',5' cyclic adenosine monophosphate (8-ClcAMP). MATERIALS AND METHODS: Cytogenetic effects of 8-Cl-cAMP where evaluated using the in vitro chromosome cytogenetic assay (CA) on human peripheral blood lymphocytes of healthy individuals and by bone marrow micronucleus assay in adult BALB/c mice. RESULTS: In the in vitro chromosome CA, 8-Cl-cAMP (in all respective doses; 1.5 and 15 microm) induced mitotic inhibition and premature centromere separation (PCS) but no chromosomal damage in cultured human peripheral blood lymphocytes. In the in vivo test, single intraperitoneal (i.p.) injection of 8-Cl-cAMP in doses of 10, 80 and 150 mg/kg showed a dose-related effect on the frequency of micronuclei, detected in murine polychromatic erythrocytes (PCE). CONCLUSION: The results of the present study show that genotoxicity of 8-Cl-cAMP has a different matrix of response when comparing results in vitro and in vivo, suggesting that high metabolic activity in vivo is responsible for the clastogenic potential of 8-Cl-cAMP. These comparative results indicate a need of having an available battery of genotoxic tests in order to evaluate possible cytogenetic effects of novel antitumor agents.

Relation of matrix metalloproteinase-9 to different stages of tumors in the serum of gastric cancer.

The sera of 40 patients with gastric cancer and 11 patients as the control group were studied for the detection of matrix metalloproteinases. The malignant behavior of tumor cells mainly depends on the capability of invasion and the metastasis of cancer cells. After the components of the extracellular matrix (ECM) are degraded, tumor cells invade the surrounding tissue and the vascular or lymphatic vessels to form metastasis colonies at distant sites. Extracellular proteolytic enzymes implicate the invasion and metastasis of cancer. Proteolytic enzymes from tumors lead to the breakdown of basement membranes and the ECM, thereby, facilitating cancer cell invasion into the surrounding normal tissue. Proteinase activity is overexpressed in the serum of stage 3 and 4 tumors compared to stage 1 and 2 tumors. ProMMP-9 was detected in the serum of patients of gastric cancer by SDS polyacrylamide gel electrophoresis (SDS-PAGE) and SDS-PAGE zymography, with its molecular mass of 92 kDa. MMP-9 in serum plays an important role in the progression of gastric cancer.

A study on the genotoxic effects of 8-Cl-cAMP on human lymphocytes in vitro.

8-chloro-cyclic adenosine 3',5'-monophosphate (8-Cl-cAMP) is the most potent cAMP analogue that selectively inhibits a variety of cancer cell lines in vitro and tumors in vivo. Its action toward a variety of tumors, especially when coupled with other antitumor agents, have lead to phase I clinical investigations and recently phase II clinical investigations. Until today very little was done to evaluate its genotoxic potential. In order to evaluate its genotoxic potential we used the cytogenetic and cytokinesis block micronucleus assay in vitro on peripheral blood lymphocytes of healthy individuals. Using three concentrations (1 microM, 5 microM and 15 microM), 8-Cl-cAMP in normal human peripheral blood lymphocytes did not induce any cytogenetic aberrations of the structural type [chromatid breakage, isochromatid breakage and gaps], but did induce premature centromere separation (PCS) in all respective doses and increased the frequency of micronuclei (p <0.05) only in the highest dose (15 microM). Antiproliferative action of 8-Cl-cAMP was estimated by using the cytokinesis block nuclear division index (NDI). The results showed a decrease in the NDI of cells exposed to all doses of 8-Cl-cAMP when compared to control. Therefore, the overall results show a genotoxic potential of 8-Cl-cAMP in peripheral blood lymphocytes in vitro.

Deregulated sequential motion of centromeres induced by antitumor agents may lead to genome instability in human peripheral blood lymphocytes.

PURPOSE: Segregation of chromosomes in anaphase is preceded by a sequential order of centromere separation. Alteration of the sequence of centromere separation or premature centromere division (PCD) has been found to be significantly higher in populations exposed to various xenobiotics. The purpose of this study was to investigate if PCD induced by various cytostatics can alter the stability of chromosomes and lead to aneuploidy. MATERIALS AND METHODS: Peripheral blood lymphocytes of 10 healthy, non smoking subjects were exposed to 8-Cl-cAMP at a dose of 1, 5 and 15 microM, paclitaxel at a dose of 0.01, 0.05 and 0.2 microM, and cycloheximide (CX) at a dose of 5, 10 and 25 microg/ml. By using the cytohalasin B (CB)-micronucleus (MN) test in vitro, in combination with fluorescent in situ hybridization (FISH), the presence of MN was analyzed in 1000 binuclear cells for each experimental and negative control group. For analysis of MN content we used the alpha-centromeric probe for chromosome 18. RESULTS: 8-Cl-cAMP and paclitaxel induced an increase in the frequency of MN in peripheral blood lymphocytes. 8-Cl-cAMP and paclitaxel proved clastogenic, i.e. they increased the frequency of MN and induced PCD in all respective doses. CX proved not clastogenic in the respected doses when using the CB-MN test in vitro, although CX is a specific PCD inducer. No correlation of PCD and aneuploidy of chromosome 18 was found in cells exposed to 8-Cl-cAMP and paclitaxel by using FISH. In cells exposed to CX we found PCD of chromosome 18 in binuclear cells and single signals in scarce MN. These findings were not statistically significant compared to the negative control group. CONCLUSION: Our results show that the properties of the investigated antitumor agents to induce PCD in peripheral blood lymphocytes and, therefore, aneuploidy and genome instability, is highly based on the nature of the alteration of centromere function, i.e. the temporal order of centromere kinetics are more regulated through the sequence of centromere separation than by the segregation processes. We suggest that PCD induced by novel antitumor agents could be included in preclinical and clinical genetic risk assessment analysis.

Microstructural characteristics of calcium hydroxyapatite/poly-L-lactide based composites.

Besides its high osteoinductive properties, hydroxyapatite (HAp) exhibits a relatively low mechanical strength. In order to improve the mechanical properties and reliability of HAp based composites, the addition of selected polymers is highly recommended. The main objective of this work is to study the microstructural characteristics of HAp/poly-L-lactide (PLLA) composites obtained by cold or hot processing. The composites were prepared from a mixture of a chloroform solution of poly-L-lactide with granulated HAp. After elimination of chloroform by vacuum evaporation, dense compacts were obtained by cold or hot pressing. The pressing pressure ranged from 98.10 to 294.3 MPa for both cold and hot pressing. The hot pressing was performed in the temperature region 293-457 K for a time period of 15-60 min. Depending on the PLLA amount and the pressing procedure it is possible to obtain highly porous or nearly fully dense composites. The scanning electron microscopy examination of fracture as well as of free surfaces revealed that the final porosity and wetting are affected to a great extent by the synthesis conditions and amount of polymer added. An increase in temperature to 457 K for a longer period of time results in fully dense compacts. The formation of a nearly continuous polymer network that leads to the hardening of HAp has also been observed. However, it should be pointed out that some layers of HAp may be free of polymer film since PLLA penetrates more deeply into the porous HAp.

[Psychological impact of presence of an implantable catheter in patients with serious illnesses]. / Retentissement psychologique de la présence d'une chambre implantable chez un patient atteint de maladie grave.

Implantation of an infusion device propels the patient into the world of serious disease, uncertainty, and burdensome treatments. A repository for anxiety and fear, the device will remain a foreign body perceived as beneficial at some times and threatening at others, and as a source of distress. Although it provides greater comfort, self-sufficiency, and freedom from treatment-related constraints, it modifies or even disrupts the relationship with health care providers, causing the patient to feel ensnared in the meshes of submission to and dependency on disease and the medical profession. To find some measure of relief from anxiety and to cushion the blow of this new reality, the patient uses coping mechanisms that are often surprisingly complex. The physicians and other health care professionals who provide support to their patients, remaining close to their psychological reality, are faced with the difficult task of reconciling the psychological effects of perfusion device implantation with imperative therapeutic needs.