[Predictors of success in smoking cessation among participants of spirometric screening for COPD]. / Czynniki okreslajace sukces w porzucaniu palenia u osób uczestniczacych w srodowiskowych badaniach spirometrycznych.

The aim of the study was to evaluate factors that could predict smoking cessation after a minimal antismoking counseling during spirometric screening for COPD. Every subject filled-in a simple questionnaire on clinical signs of COPD and tobacco habit, had a spirometry performed according to ATS standards and received a short antitobacco counseling together with a booklet on how to quit smoking. Out of 800 smokers over 40 years of age, smoking history of more than 10 packyears, screened for COPD in 1999, four hundred were invited a year later for a follow-up spirometry and evaluation of anti-smoking intervention. Of 383 patients, who responded to the invitation (208 M and 175 F, mean age 56.6 +/- 10.7 yrs), 52 (13.6%) quit smoking for one year and another 48 (12.5%) quit smoking temporarily and than resumed smoking. Smokers who permanently succeeded in quitting smoking were older (60.5 vs 55.9 years p < 0.01), started smoking later (age at starting smoking 22 vs 19.5 years p < 0.001), had a shorter tobacco exposition (28.8 vs 34.3 packyears p < 0.05), had lower lung function (FEV1%pred 80.5 vs 89.2% p < 0.05) and were less nicotine dependent (FTQ score 1 vs 4.8 p < 0.00001).

Calponin inhibits actin-activated MgATPase of myosin subfragment 1 (S1) without displacing S1 from its binding site on actin.

Calponin is a smooth-muscle thin-filament protein implicated in the regulation of contraction. Its binding to actin is a prerequisite for inhibition of actin-activated myosin MgATPase. Investigating the molecular mechanism of this inhibition, it was found that titration of acto-myosin subfragment 1 with calponin in the presence of either ADP or ATP does not displace weakly or strongly bound myosin subfragment 1 (S1) from actin. S1.ADP, however, is able to release about two-thirds of the calponin from saturated (equimolar) complexes of actin-calponin. The remaining calponin is sufficient for almost full inhibition of acto-S1 MgATPase activity. Bunding of actin filaments by calponin takes place at a higher ratio calponin/actin (above 1:3) and, therefore, is not responsible for inhibition of the ATPase. Bundle formation is inhibited by S1.ADP. These results suggest the existence of two calponin-binding sites on actin; one, that is insensitive to S1, which is responsible for inhibition of the ATPase, the other, from which calponin is readily displaced by S1.

Interaction of calponin with actin and its functional implications.

Titration of F-actin with calponin causes the formation of two types of complexes. One, at saturation, contains a lower ratio of calponin to actin (0.5:1) and is insoluble at physiological ionic strength. The another is soluble, with a higher ratio of calponin to actin (1:1). Electron microscopy revealed that the former complex consists of paracrystalline bundles of actin filaments, whereas the latter consists of separate filaments. Ca(2+)-calmodulin causes dissociation of bundles with simultaneous increase in the number of separate calponin-containing filaments. Further increase in the calmodulin concentration results in full release of calponin from actin filaments. In motility assays, calponin, when added together with ATP to actin filaments complexed with immobilized myosin, evoked a decrease in both the number and velocity of moving actin filaments. Addition of calponin to actin filaments before their binding to myosin resulted in a formation of actin filament bundles which were dissociated by ATP.

Lys-373 of actin is involved in binding to caldesmon.

Limited proteolysis of actin with trypsin removes its two or three C-terminal amino acid residues [Proc. Natl. Acad. Sci. USA 81 (1984) 3680-3684]. Carboxypeptidase B-treatment of G- and F-actin previously digested with trypsin revealed that in the first case preferential release of three and in the second two C-terminal amino acid residues takes place. Tryptic removal of three but not two C-terminal amino acid residues of actin causes weakening of its interaction with caldesmon and lowering of the caldesmon-induced inhibitory effect on actomyosin ATPase activity. Therefore, it is concluded that the third amino acid residue from the C terminus of actin, Lys-373, is important for the interaction with caldesmon.

The importance of C-terminal amino acid residues of actin to the inhibition of actomyosin ATPase activity by caldesmon and troponin I.

Proteolytic elimination of three C-terminal amino acid residues from actin weakens its interaction with caldesmon and troponin I and, in consequence, lowers the inhibitory effects of both proteins on actomyosin ATPase activity. These results prove the importance of C-terminal extremity of actin to the overall interaction of this protein with caldesmon and troponin I.

Neurotoxic effects of the combined exposure to carbon disulphide and ethanol in rats.

Neurotoxic effects of the combined exposure of rats to carbon disulphide (CS2) and ethanol (EtOH) were studied. Biochemical and ultrastructural evaluation of the central nervous system (CNS) and peripheral nervous system (PNS) was performed. Male Wistar rats were exposed to CS2 vapour (0.8 mg/l air) and to 10% alcohol in the drinking water for 8 months. EtOH elevated the increase in beta-glucuronidase activity caused by CS2 in the hippocampus and in the cerebral cortex. No effect on the high-affinity synaptosomal uptake of L-glutamate and GABA was observed and no marked ultrastructural changes in the tested brain regions were found. In the peripheral nerves CS2 alone evoked axonal degeneration whereas CS2 combined with EtOH caused disturbances in myelin. Ultrastructural changes preceded biochemical alterations in the PNS and the biochemical indicators of peripheral neuropathy such as beta-glucuronidase activity and cholesterol ester content were not significantly affected. It is suggested that CS2 and EtOH combined affect both PNS and CNS to a higher extent than each of these substances alone.

[Experimental studies of acute and chronic toxic effects of vinyl acetate]. / Badania doswiadczalne nad ostrym i przewleklym dzialaniem toksycznym octanu winylu.

In view of divergent opinions concerning MAC value for vinyl acetate, a study on acute and chronic inhalatory toxic effect of this compound on animals was carried out. The scope of the study included determination of CL50 value after Litchfield and Wilcoxon and 10-month exposure of animals to vinyl acetate at concentrations 10, 100 and 500 mg/m3, 5 days weekly, 5 hours daily. During 10-month experiment the animals were observed and body weight controlled. In addition, periodically some hematological examinations and biochemical of blood serum as well as histopathological examinations of inner organs were carried on. Post-mortally the weight of inner organs was determined. CL50 value determined on rats has amounted to 4100 ppm. In the study on chronic effect, the prevalence and the degree of intensity of the changes of the used by us indicators was the least in the group of animals exposed to vinyl acetate at concentration of 10 mg/m3. These changes were transient not involved reticulopenia and animals' body weight decrease. Histopathological examinations revealed some inflammatory changes in respiratory system both in control and exposed animals. Only planoepithelial metaplasia of bronchi was found exclusively in animals exposed to vinyl acetate at all concentrations used. The changes within liver were found only in animals exposed to vinyl acetate at concentration of 100 and 500 mg/m3. These changes involved fatty degeneration of hepatic parenchyma, proliferation and extension of smooth endoplasmatic reticulum and the changes within the biliary canaliculi. Taking the above results into account it seems that the lowest of the recommended in the world MAC value--10 mg/m3 may be accepted as the upper limit of the maximum admissible concentration for vinyl acetate.

Comparative studies of fibrogenic properties of wollastonite, chrysotile and crocidolite.

Fibrogenous effects of wollastonite, chrysotile and crocidolite have been investigated in experiments on animals. (Wollastonite is a calcium silicate of fibrous structure, occasionally applied as asbestos substitute). The experimental animals were intratracheally administered single doses of 50 mg of the test material suspended in 0.6 ml of physiological NaCl solution. The animals were decapitated 3, 6 and 9 months after the experiment. Fibrogenic properties were evaluated basing on the weight of wet lungs, content of lipids and hydroxyproline in lungs, as well as histopathological tests of lungs, mediastinal lymph nodes and spleen. Histopathological preparations were evaluated using an optical, microscope or transmission electron microscope. The findings of biochemical, pathomorphological, and ultrastructural studies demonstrated slight fibrogenic effects of wollastonite, as compared to chrysotile and crocidolite.

Effect of alcohol intake on some disturbances induced by chronic exposure to carbon disulphide in rats. II. Biochemical and ultrastructural alterations in the peripheral nerves.

The effect of chronic ethanol (EtOH) administration on CS2-induced peripheral neuropathy in rats was studied. Rats were exposed to 0.8 mg/l CS2 for 12-15 months and to 10% EtOH as only drink during the last 4 months of the experiment. Some biochemical correlates of Wallerian degeneration of the peripheral nerve were estimated and ultrastructural examinations of the peripheral nerves were performed. It was shown that EtOH augmented the alterations in lipid content provoked by CS2 in the peripheral nerves, i.e. an increase in cholesterol esters and in the ratio of cholesterol esters to free cholesterol (E/F ratio) and a decrease in phospholipid content. The magnitude of ultrastructural changes induced by CS2 in the nerves was increased by EtOH.

Stimulation of lipid peroxidation and heme oxygenase activity with inhibition of cytochrome P-450 monooxygenase in the liver of rats repeatedly exposed to cadmium.

Exposure of rats to 0.1 and 0.5 mg Cd/kg subcutaneously (s.c.) thrice weekly for 5 weeks resulted in an accumulation of cadmium in the liver in concentrations of 40 and 95 micrograms/g tissue, respectively, and a microsomal burden of Cd amounting to approx. 2-3% of the retained cadmium. The cytoplasm contained about 80% of the cadmium. At an exposure dose of 0.1 mg Cd/kg, stimulation of lipid peroxidation by 22% and inhibition of ALA synthetase by 16% in the liver were observed. The higher exposure of 0.5 mg Cd/kg caused an inhibition of microsomal monooxygenase with depression of cytochrome P-450 and cytochrome b5 by 20% (over 2-fold prolongation of hexobarbital sleeping time and statistically significant decrease of activity of aniline p-hydroxylase). The loss of cytochrome P-450 probably was due to an intensified lipid peroxidation and induction of heme oxygenase (30% and 60% over control, respectively). Sequestration of cadmium by cytoplasm (metallothionein) does not protect microsomes against cadmium accumulation and specific biochemical disturbances.

Effect of long-term inhalation exposure to cadmium oxide fumes on cardiac muscle ultrastructure in rats.

The ultrastructure of the cardiac muscle of rats exposed 5 h daily, 5 days a week to cadmium oxide (CdO) fumes at a concentration of 0.16 mg Cd/m3 for 3 and 6 months and at a concentration of 1 mg Cd/m3 for 3 and 4 months has been evaluated. The structure of muscle cells, arterioles and capillaries remained unchanged. There were distinct alterations of the intercalated disc structure dependent upon the level and time of exposure. The damage to intercalated discs varied from the enlargement of the fissure between membranes (within unspecialized segments) to disruption of the complex junctions.

Effect of different conditions of acute exposure to carbon monoxide on the cerebral high-energy phosphates and ultrastructure of brain mitochondria in rats.

Rats were exposed to carbon monoxide (CO) in different conditions: 4 min at 1.3% CO, 40 min at 0.5% CO or 12 h at 0.13--0.15% CO. After 4 min exposure to 1.3% CO the brain content of ATP and PC was substantially reduced; after 40 min exposure to 0.5% CO the cerebral ATP level was slightly increased, whereas the content of both ATP and PC in the brain of rats exposed to CO for 12 h was significantly higher than in the controls. The decrease in the brain level of ATP and PC after 4 min exposure to 1.3% CO was accompanied by ultrastructural changes of mitochondria. No evident differences in the level of cerebral high-energy phosphates were found between rats intoxicated with CO and rats subjected to experimental hypoxemia.

The content of high-energy phosphates and ultrastructure of mitochondria in the brain of rats exposed to carbon disulphide.

Rats were exposed to carbon disulphide (CS2) continuously for 12 h or for 10 months, at concentrations of 2.4 mg/l air and 0.8 mg/l air, respectively. No changes in the brain content of ATP, ADP and AMP were found in rats after chronic exposure, whereas the content of ATP in the brain of rats acutely poisoned with CS2 was significantly higher (21%) accompanied by decrease in the content of ADP (10%) and AMP (45%). The biochemical changes were accompanied by ultrastructural changes of mitochondria, particularly those in the cerebellar perikaryons.

Experimental studies on the chronic toxic effects of vinyl chloride in rats.

Male rats were exposed to vinyl chloride at the concentrations of 50, 500, and 20 000 ppm, 5 hours daily, 5 days a week for 10 months. Morphological lesions in the liver and the testes detected by light and electron microscope and depression in body weight increase intensified with the duration of exposure. Increased relative weights of some organs and slight hematological and biochemical changes in blood during the course of the experiment were also observed. Some toxic effects including morphological liver injuries arose at the smallest exposure level, i. e., 50 ppm. Assuming 50 ppm as the threshold concentration for rats, the 5 ppm level has been estimated as the safe exposure limit in industry in relation to systemic effects of vinyl chloride.

[Lipid changes in the blood serum and arterial wall in rabbits chronically exposed to CS2]. / Zmiany lipidowe w surowicy i scianie tetnicy u królików narazonych na przewlekle dzialanie CS2.

In the studies carried out lipids content in blood serum and aorta wall as well as morphological changes in coronary vessels of CS2 exposed rats have been evaluated. The 10-month-exposure to CS2 at a concentration of 0,8--0,9 mg/l has been found to result in: (1) increased concentration of total and free cholesterol, cholesterol esters, triglycerides and phospholipids in blood serum; (2) increase in total cholesterol and significant rise in the level of cholesterol esters in the aorta wall; (3) a relative increase in serum VLDL, LDL and decrease in HDL fraction. Histological estimation has demonstrated in serial sections of hearts of the CS2 exposed animals thickened walls of left coronary artery branches with no lipid deposits. In two animals focal steatosis of aortic bulb wall and aortic valves and lipids droplets in endothelium of ascending aorta and coronary vessels have been found.

Monooxygenase activity and ultrastructural changes of liver in the course of chronic exposure of rats to vinyl chloride.

The activity of microsomal cytochrome P-450 monooxygenase and ultrastructure of the liver have been studied in rats exposed dynamically to 50, 500, and 20,000 ppm of vinyl chloride (VC) over 10 months. After 1 and 3 months of exposure to 500 and 20,000 ppm of VC, the level of cytochrome P-450 was slightly lower than in the control animals and upon continuation of exposure it was restored to the original level accompanied by slight increase of activity of aniline p-hydroxylase. Liver enlargement, developed in the course of the exposure, was accompanied by ultrastructural alterations beginning in the 3rd month of exposure to all concentrations of VC. Development of hepatic alterations (hypertrophy of smooth and rough endoplasmic reticulum, swelling of mitochondria, accumulation of lipid droplets, focal cytoplasmic degradation) is discussed with regard to the activity of microsomal monooxygenase system in metabolizing VC to toxic metabolites.

[Experimental silicosis. I. Fibrogenic effect of synthetic amorphous silica]. / Doswiadczalna pylica krzemowa. I. Dziallanie zwlokniajace syntetycznych krzemionek bezpostaciowych.

Fibrogenic properties of two dusts of synthetic hydrated amorphous silicas, Ze-O-Sil (French production) and Arsil (Polish production) were studied. Experimental silicosis was induced by intratracheal administration to rats of a single dust dose (50 mg in 0.6 ml NaCl). Fibrogenic properties were tested 3, 6, 9 months after administration of the dust. X-ray diffraction and chemical tests did not reveal any form of crystalline. Si02 in the composition of the investigated dusts. The dusts tested as compared with quartz, were characterized by a great solubility up to 211 mg/l, which made the dust excretion from the lungs easy; after 6 month-experiment approximately 1.2 mg of Arsil dust and about 28 mg of quartz dust residue was found. Fibrogenic properties of Arsil dust, represented by wet lungs weight increase and hydroxyproline content in lungs, were more pronounced than those of Ze-O-Sil. Hydroxyproline content 3 months after administration of Arsil, Ze-O-Sil, TiO2 and weak quartz amounted to 7.3 mg, 5.1 mg, 3.8 mg and 6.0 mg, respectively. Histological and ultrastructural investigations demonstrated that disseminated, multifocal granulomas were the basic reaction to both dusts; no clear histological signs of cytolytic action on the cells of dust granulomas were found. In the lungs no silicotic nodules or degeneration of changes were revealed. Neither biochemical tests nor histological examinations revealed a progressive development of fibrous connective tissue. In result of the studies the authors suggest 2 mg/m3 as a MAC value for Arsil dust instead of 10 mg/m3--the value which has been hitherto used.