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Biomedical subjects

R Turk

Publications and source records attributed to R Turk.

At least 19 recordsLinked to original sources

Common pathological mechanisms in mouse models for muscular dystrophies.

Duchenne/Becker and limb-girdle muscular dystrophies share clinical symptoms like muscle weakness and wasting but differ in clinical presentation and severity. To get a closer view on the differentiating molecular events responsible for the muscular dystrophies, we have carried out a comparative gene expression profiling of hindlimb muscles of the following mouse models: dystrophin-deficient (mdx, mdx(3cv)), sarcoglycan-deficient (Sgca null, Sgcb null, Sgcg null, Sgcd null), dysferlin-deficient (Dysf null, SJL(Dysf)), sarcospan-deficient (Sspn null), and wild-type (C57Bl/6, C57Bl/10) mice. The expression profiles clearly discriminated between severely affected (dystrophinopathies and sarcoglycanopathies) and mildly or nonaffected models (dysferlinopathies, sarcospan-deficiency, wild-type). Dystrophin-deficient and sarcoglycan-deficient profiles were remarkably similar, sharing inflammatory and structural remodeling processes. These processes were also ongoing in dysferlin-deficient animals, albeit at lower levels, in agreement with the later age of onset of this muscular dystrophy. The inflammatory proteins Spp1 and S100a9 were up-regulated in all models, including sarcospan-deficient mice, which points, for the first time, at a subtle phenotype for Sspn null mice. In conclusion, we identified biomarker genes for which expression correlates with the severity of the disease, which can be used for monitoring disease progression. This comparative study is an integrating step toward the development of an expression profiling-based diagnostic approach for muscular dystrophies in humans.

Animals↗

Muscle regeneration in dystrophin-deficient mdx mice studied by gene expression profiling.

BACKGROUND: Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is lethal. In contrast, dystrophin-deficient mdx mice recover due to effective regeneration of affected muscle tissue. To characterize the molecular processes associated with regeneration, we compared gene expression levels in hindlimb muscle tissue of mdx and control mice at 9 timepoints, ranging from 1-20 weeks of age. RESULTS: Out of 7776 genes, 1735 were differentially expressed between mdx and control muscle at at least one timepoint (p < 0.05 after Bonferroni correction). We found that genes coding for components of the dystrophin-associated glycoprotein complex are generally downregulated in the mdx mouse. Based on functional characteristics such as membrane localization, signal transduction, and transcriptional activation, 166 differentially expressed genes with possible functions in regeneration were analyzed in more detail. The majority of these genes peak at the age of 8 weeks, where the regeneration activity is maximal. The following pathways are activated, as shown by upregulation of multiple members per signalling pathway: the Notch-Delta pathway that plays a role in the activation of satellite cells, and the Bmp15 and Neuregulin 3 signalling pathways that may regulate proliferation and differentiation of satellite cells. In DMD patients, only few of the identified regeneration-associated genes were found activated, indicating less efficient regeneration processes in humans. CONCLUSION: Based on the observed expression profiles, we describe a model for muscle regeneration in mdx mice, which may provide new leads for development of DMD therapies based on the improvement of muscle regeneration efficacy.

Adolescent↗

Serum paraoxonase activity in dairy cows during pregnancy.

Preparturient dairy cows are at high risk of metabolic and reproductive disorders and oxidative stress is considered to be involved in these events. We investigated the serum paraoxonase activity in dairy cows during pregnancy and alterations in lipid and lipoprotein patterns in this period. The relation between paraoxonase activity and HDL-cholesterol concentration was also compared. The study was carried out on 76 pregnant lactating and 26 pregnant dry Holstein dairy cows. The serum paraoxonase activity was determined by the method of hydrolysing of paraoxon, while triglyceride, cholesterol and HDL-cholesterol concentrations were measured by the enzymatic kit methods. A significantly higher serum triglyceride concentration (P<0.001) was observed in dry cows compared to lactating cows. The total cholesterol and HDL-cholesterol concentrations were significantly lower (P<0.001) in dry cows than in lactating ones. In dry cows, paraoxonase activity was significantly lower than in those lactating (P<0.001). There was no significant difference in paraoxonase/HDL-cholesterol ratio between the investigated groups. It seems that the lower HDL concentration could be one of the causes of reduced paraoxonase activity considering the role of HDL as a carrier of most paraoxonase molecules in the blood. A decreased serum paraoxonase activity could diminish the effectiveness and total capacity of the whole antioxidative system during prepartum period in dairy cattle.

Animals↗

Serum paraoxonase activity and lipid parameters in the early postpartum period of dairy cows.

The effect of early lactation on serum paraoxonase activity was studied on 21 postpartum dairy cows and 19 non-pregnant late lactating dairy cows. A significant decrease of the paraoxonase activity was found in the early postpartum period compared to the late non-pregnant lactation. The serum triglyceride, cholesterol and LDL-cholesterol concentration were also markedly reduced during the postpartum period, while the serum HDL-cholesterol concentration showed no significant change. The results indicate that lower serum paraoxonase activity is associated with lipid metabolic disorders in the early postpartum period. A decreased serum paraoxonase activity may lead to the reduction of the antioxidative capacity and antioxidative protection during the early postpartum period.

Animals↗

Study of some immunological parameters in workers occupationally exposed to benzene.

OBJECTIVE: The aim of the study was to investigate the immunotoxicity of benzene exposure, to establish the correlation between the exposure biomarkers and some immunological parameters, and to assess the possible influence of confounding factors on the results of immunological assay applicable in routine medical surveillance of benzene-exposed workers. METHODS: Forty-nine female workers in the shoemaking industry who were exposed to solvent mixtures and 27 nonexposed controls were examined. Workers were exposed to benzene concentrations of up to 15 ppm, and to toluene of up to 50 ppm. RESULTS: Significant differences in the levels of benzene and toluene in blood and phenols in post-shift urine between the exposed and the control group confirmed solvent exposure. The number of B-lymphocytes (P = 0.01) was lower in the shoe workers than in the controls. Significant correlation was found between the level of immunoglobulin G and benzene in the work atmosphere, while confounding factors had no impact on immunological values. CONCLUSION: According to these results, exposure to benzene concentration lower than 15 ppm can induce depression of the circulating B-lymphocyte level and therefore this fact could be used to develop a promising method for health surveillance of benzene-exposed workers. However, considerably more effort in the research on benzene immunotoxicity, especially in the search for suitable health surveillance methods, is still required.

Adult↗

Occupational histamine poisoning by fish flour: a case report.

Histamine poisoning due to inhalation and skin contact with fish products is rarely described in the literature. This study presents a case of occupational histamine poisoning by spoiled fish flour via inhalation, skin and eye contact. Shipments of fish flour transported in black or blue bags, depending on the source, were handled by 20 harbour workers. Ten workers handling blue bags developed allergy-like skin, eye, gastrointestinal, respiratory and cardiac symptoms within 30 min. Workers handling black bags were symptom-free, except for minimal eye irritation. After consultation with the Poison Control Centre histamine poisoning was suspected. The histamine content, as determined by thin-layer chromatography, was 10-fold higher in samples from the blue than from the black bags (510 mg/100 g flour compared with 50 mg/100 g flour, respectively). Part of the shipment was labelled as hazardous for human health with permission for further usage only under specific personal protective measures. It is suggested that the highest permissible levels of histamine in fish flour and similar products should be set and legally adopted.

Adult↗

The changing pattern of poisoning with psychoactive drugs in Croatia.

The aim of this study was to analyse the frequency of poisoning with psychoactive drugs (benzodiazepines, antidepressants and neuroleptics) over the last 15 years in Croatia. The analysis was based on poisoning incidents reported over the phone (hot line) to the Zagreb Poison Control Center and included two periods: 1985-1991 (period I) and 1992-1999 (period II). The data were analysed separately for children and adults. Each phone call was counted as one poisoning incident. Child poisoning with neuroleptics was significantly higher in period II than in period I and so was the adult poisoning with antidepressants, amytriptyline, and combined psychoactive drugs. The frequency of total psychoactive drug poisoning was significantly higher in adults than in children in both periods. From 1992, the frequency of adult poisoning with antidepressants considerably increased as one of the many consequences of war-related stress. The results indicate a need for careful psychiatric evaluation and more critical use of antidepressants in affected individuals.

Adult↗

Household chemicals--common cause of unintentional poisoning.

Of 4736 poisoning incidents registered in the Poison Control Centre in Zagreb from 1985 to 1999, household chemicals caused 23%. In the group of cleaning products, 11% of poisoning incidents were caused by corrosives, 9% by liquid detergents and 4% by hypochlorite. Organic solvents caused 18% of household chemical poisonings; among them gasoline and thinners were the most frequent. Cosmetics were responsible for 7% of poisoning incidents; the most frequent were hair shampoo, hydrogen peroxide, and acetone. In the group of other chemicals, the most common were ingestion of thermometer mercury and of silica gel, while poisonings with highly toxic antifreeze, mothballs, or liquid fertilisers were rare. Ingestion or other exposure to household chemicals often caused excessive concern and therapeutic measures. It is therefore advisable to consult a Poison Control Centre in order to get proper information about the composition of a chemical and toxicity of a product.

Child↗

Service utilization and cost of community care for discharged state hospital patients: a 3-year follow-up study.

OBJECTIVE: This study examined the mental health service utilization and costs of 321 discharged state hospital patients during a 3-year follow-up period compared with costs if the patients had remained in the hospital. METHOD: The study subjects were long-stay patients discharged from Philadelphia State Hospital after 1988. A longitudinal integrated database on all mental health and medical services reimbursed by Medicaid and Medicare as well as state- and county-funded services was used to construct service utilization and unit cost measures. RESULTS: During the 3-year period after discharge, 20%-30% of the patients required rehospitalization an average of 76-91 days per year. The percentage of rehospitalized patients decreased over time, but the number of hospital days increased. All of the discharged patients received case management services, and a majority also received outpatient mental health care (66%-70%) and residential services (75%) throughout the follow-up period. The total treatment cost per person was approximately $60,000 a year after controlling for inflation, with costs rising slightly over the 3-year period. The estimated cost of state hospitalization, with the use of 1992 estimates, would have been $130,000 per year if the patients had remained institutionalized. CONCLUSIONS: This analysis suggests that most former long-stay patients are able to live in residential settings while receiving community outpatient treatment and intensive case management services at a reduced cost. There is no indication of cost shifting from the psychiatric to the health care sector; however, some cost shifting from the state mental health agency to the Medicaid program has occurred, since most psychiatric hospital care now takes place in community hospitals.

Adult↗

Quantitative assessment of color vision impairment in workers exposed to toluene.

Color vision was examined by the Lanthony-D-15 desaturated test in two groups of workers occupationally exposed to toluene and in a control group. Biological parameters of toluene exposure were analyzed: toluene in air and in venous blood, orthocresol, and hippuric acid in urine after workshift. The first exposed group, Group E1, comprised 41 workers (toluene exposure ranged from 11.30 to 49.30 ppm), and the second exposed group, Group E2, comprised 32 workers (toluene exposure ranged from 66.00 to 250.00 ppm). The nonexposed group, Group NE, comprised 83 subjects. Each group was divided into two subgroups; alcohol consumers and nonconsumers. Color vision loss was expressed as a color confusion index (CCI) and as age and alcohol intake-adjusted color confusion index (AACCI). Significantly higher values of CCI and AACCI (both P < 0.0001) in Group E2 in comparison to Group NE, and significantly higher CCI (P < 0.0001) and AACCI (P < 0.05) values in Group E2 in comparison to Group E1 were established. The significant difference in CCI value between alcohol consumers and nonconsumers was established only in Group NE (P < 0.05). In Group NE significant correlation was found between CCI value as a dependent and age and alcohol intake as independent cofactors (R2 = 0.45; P = 0.0000). In Group E2 significant correlation was established between CCI as a dependent factor and age, toluene in air, and alcohol intake (R2 = 0.72; P = 0.0001), or between CCI as dependent and age, toluene in blood and alcohol intake as independent cofactors (R2 = 0.68; P = 0.0002). In Group E1 significant correlation was established only between CCI and age (P <0.005). In Group E2, AACCI value significantly correlated with toluene in air (P < 0.0001), toluene in blood (r < 0.0005), orthocresol (P < 0.005) and hippuric acid (P < 0.005) in urine after workshift. There were no differences between smokers and nonsmokers in CCI values in the examined groups. Results of this study indicate that toluene in exposed workers can impair color vision. The role of alcohol intake and age influence on color vision loss cannot be ignored in such workers.

Adult↗

Qualitative color vision impairment in toluene-exposed workers.

OBJECTIVE: The aim of this study was to evaluate whether toluene, like many other organic solvents and solvent mixtures, could impair color vision. SUBJECTS AND METHODS: We investigated color vision impairment in three groups of workers, two groups occupationally exposed to toluene and a nonexposed group. The first exposed group, group E1, comprised 41 workers (median value of toluene in air 35.00 ppm, range 11.3-49.3 ppm) and the second exposed group, group E2, comprised 32 subjects (median value of toluene in air 156.00 ppm, range 66.0-250.0 ppm). The nonexposed group, group NE, comprised 83 subjects. Color vision was evaluated by the Lanthony D-15 desaturated test according to Verriest's classification: type I, loss in the red-green range; type II, loss in the blue-yellow and red-green ranges, and type III, loss in the blue-yellow range. Subjects were classified as dyschromates if specific acquired loss was determined in at least one eye. In both exposed groups, exposure was evaluated by measurement of the concentration of toluene in the ambient air and in the blood. In group E2, level of hippuric acid and orthocresol in urine after the work shift were also determined. The Mann-Whitney U-test, t-test, chi 2-test, and Spearman's rank correlation and multiple regression analysis were used for statistical analysis. RESULTS: Type III dyschromatopsia was detected in all groups examined: 26.6% of the workers in group NE, 31.7% of those in group E1, and 50% of those in group E2. As many as 15.6% of the workers in group E2, 4.8% of those in group E1, and only 1.2% of those in group NE had type II dyschromatopsia. A statistically significant difference in the prevalence of total dyschromatopsia (type III + type II) was established among the three examined groups together (chi 2 = 14.13; df = 2; P < 0.01), between group E2 and group E1 (chi 2 = 4.96; P < 0.05), and between group E2 and group NE (chi 2 = 12.50; P < 0.005), whereas no significant difference was found between groups E1 and NE. Type III dyschromatopsia was significantly correlated with age in group NE (P < 0.01) and in group E1 (P < 0.005). In group E2, both type II (P < 0.05) and type III dyschromatopsia correlated with toluene in ambient air and with the duration of exposure to toluene (both P < 0.005). In group E2, total dyschromatopsia correlated significantly with toluene in ambient air and in blood (both P < 0.05) as well as with hippuric acid in urine after the work shift (P < 0.001). CONCLUSION: This study suggests that toluene can impair color vision.

Adult↗

Assessment of colour vision impairment in male workers exposed to toluene generally above occupational exposure limits.

We investigated colour vision impairment in 45 male workers occupationally exposed to toluene (mean value of toluene concentration in ambient air = 119.96 ppm) and in 53 controls. Colour vision was evaluated by Lanthony-D-15 desaturated test and expressed as Age and Alcohol Intake Adjusted Colour Confusion Score (AACDS) or types of dyschromatopsia. Exposure was evaluated by measurement of toluene concentration in ambient air and blood, and hippuric acid and orthocresol determined in urine after the workshift. A statistically significant higher AACDS value was established in the exposed subjects compared to the controls (p < 0.0001). There was no significant difference between AACDS values on Wednesday morning compared to Monday morning. In the exposed group AACDS significantly correlated with the concentration of toluene in ambient air, concentration of toluene in blood and the concentration of hippuric acid in urine after the workshift (all p < 0.0001). Dyschromatopsias were detected in both groups, although no significant difference between groups was established. In the exposed group concentration of toluene in ambient air, alcohol intake and age explained 35.1%, concentration of toluene in blood, age and alcohol intake explained 19.9%, and concentration of hippuric acid in urine and age explained 19.2% of the variation in type III dyschromatopsia. Concentration of toluene in ambient air and age explained 28.3% of the variation in total dyschromatopsia, and concentration of hippuric acid and age explained 13.8%. In the control group, age and alcohol intake explained 19.6% of the variation in type III dyschromatopsia. In exposed workers a significant difference was found in the AACDS value compared to controls. However, no significant difference was found in the prevalence of colour vision loss in the yellow-blue and/or red-green axis. Based on the results of this study the authors conclude that the effect of toluene on colour vision can be chronic and that the possible reparation period in colour vision impairment is longer than 64 hours.

Adult↗

Secreted, glycosylated arginase from Xanthoria parietina thallus induces loss of cytoplasmic material from Xanthoria photobionts.

A secreted, glycosylated arginase (lectin) from Xanthoria parietina thallus binds to the cell wall of Xanthoria photobiont when cell wall urease has previously been induced. The uptake of this secreted arginase by the algal cell without cell wall ligand for the lectin increases the concentration of algal putrescine and it is followed by an apparent loss of chlorophyll. However, neither chlorophyllase activity has been detected nor chlorophyllide concentration increases after loading the cells with putrescine. The loss of chlorophyll can be explained by the loss of algal protoplast resulting from the action of a putrescine-activated glucanase and the split of their membrane in an hypoosmotic medium. The loss and split of protoplasts have been shown by light and transmission electron microscopy.

Arginase↗

Meso-2,3-dimercaptosuccinic acid in the treatment of occupationally exposed lead workers.

The aim of this study was to evaluate the efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) treatment in workers with increased lead absorption and no overt symptoms of lead poisoning. Seven occupationally lead exposed male workers with blood lead concentrations (PbB) exceeding 50 micrograms/100 ml and a positive calcium disodium ethylenediaminetetraacetate (EDTA) lead mobilization test were treated with DMSA for 19 days. Individual doses were 700 mg DMSA, three times a day from day one to five, and twice a day from day six to 19. The treatment intensified urinary lead excretion, most rapidly during the first five days. The increased elimination was followed by a decline of mean PbB to 15% of the pretreatment values. However, 15 days after the treatment, the PbB concentrations rebounded, yet kept below the baseline values and did not exceed 40 micrograms/100 ml. After repeated EDTA lead mobilization test, urine lead was 23-68% of that before DMSA treatment. It can be concluded that DMSA can effectively reduce chelatable lead in occupationally exposed workers.

Adult↗

Community Treatment Teams: an alternative to state hospital.

This article describes the implementation of Community Treatment Teams as a strategy to provide services to patients discharged from a state psychiatric hospital. The closing of Philadelphia State Hospital was the impetus for the development of an alternative long term care treatment system for the seriously mentally ill which was based on a variation of the community treatment team model. This article provides a description of the teams, their functioning, structure, and the impact they have had on the service system.

Adult↗

Genotoxic effects in workers exposed to benzene: with special reference to exposure biomarkers and confounding factors.

The aim of the study was to establish a correlation between biomarkers of exposure and cytogenetic test results in workers occupationally exposed to benzene and toluene, with special reference to confounding factors influencing the outcome of the cytogenetic test. The incidence of structural chromosome aberrations and sister chromatid exchanges was studied in the peripheral blood lymphocytes cell genome of 49 female shoe-makers, mean age 38 years, mean length of occupational exposure 17 years and in a group of 27 well-matched controls. Workers were exposed to concentrations of benzene up to 15 ppm and of toluene up to 50 ppm. The presence of benzene and toluene in the workers' blood samples, and the presence of phenol in pre- and post-shift urine were considered proof of occupational exposure. Chromosomal aberration analysis revealed a significant increase in dicentric incidence in the exposed group compared to the controls (P = 0.004). However, significant correlation between cytogenetic test results and the exposure biomarkers was not established. On the contrary, correlation between the cytogenetic test results and data on confounding factors (e.g. age and alcohol consumption), was marked. The major point raised by this study is the influence of confounding factors on the cytogenetic test outcome. This imposes the need for caution in the interpretation of cytogenetic test results, and ultimately in the estimation of individual genotoxicity risk related to low level benzene exposure.

Adult↗

Contribution of lead poisoning to renal impairment.

The late effects of lead on kidney function and blood pressure were studied in 38 persons occupationally poisoned in the past and in 23 workers exposed to lead. Parameters evaluated in all subjects were: creatinine clearance, hippuran renal flow, blood lead, erythrocyte protoporphyrin, aminolevulinic acid dehydratase, and blood pressure. Out of 11 combined variables, four significant factors were identified by factor analysis. The results showed the presence of the delayed adverse effect of previous occupational lead poisoning on kidney function and blood pressure. This phenomenon is a complex interplay of lead poisoning in the past, overall duration of lead exposure, and age as a major confounding variable related to aging process of the kidneys.

Adult↗

A randomized, placebo-controlled study on the effect of cyclic intermittent etidronate therapy on the bone mineral density changes associated with six months of gonadotropin-releasing hormone agonist treatment.

OBJECTIVE: Our purpose was to determine whether intermittent cyclic etidronate therapy blocks the decline in bone density associated with gonadotropin-releasing hormone agonist therapy. STUDY DESIGN: Thirty-one premenopausal subjects who needed treatment with leuprolide (Lupron) 3.75 mg monthly for 6 months were randomized to etidronate or placebo. Bone turnover was assessed by measurement of serum calcium, phosphorus, alkaline phosphatase, and fasting urinary calcium/creatinine ratios. Bone density was measured by dual energy x-ray absorptiometry. RESULTS: Gonadotropin-releasing hormone treatment produced a significant decrease (4% to 10%) in bone density at the anteroposterior and lateral spine in placebo-treated patients (11). No significant change was demonstrated in etidronate-treated patients (15). Significant increases in serum calcium, phosphorus, alkaline phosphatase, and urinary calcium/creatinine ratios were noted in the placebo group. No significant change in these parameters were evident in the etidronate group. CONCLUSION: Etidronate blocks bone mineral density changes associated with gonadotropin-releasing hormone agonist therapy and normalizes serum and urine indicators of bone turnover.

Adult↗