Effects of chronic exposure to cadmium on prostate lipids and morphology

Cadmium is an environmental toxic metal implicated in human prostate carcinogenesis. The mechanism of its toxicity is not fully understood. Previously, we showed that cadmium exposure induces oxidative stress, especially lipid peroxidation. This study evaluates the effect of chronic exposure to 0.886 mM of cadmium (Cd) per liter in the drinking water on prostate lipid content and metabolism in Wistar rats. We determined the lipid profile and measured the expression of lipogenic enzymes: FAS, GPAT, LPL, DGAT-1, DGAT-2, ACO, CPT-1 and CT, and of certain factors involved in lipid regulation and fatty acid transporters: FAT/CD36, E-FABP, SREBP-2, PPAR-γ and PPAR-α by RT-PCR. Ultrastructure was analyzed by electron microscopy and, as prostate is an androgen controlled gland, AR expression was measured by RT-PCR and Western blot. Cd altered the prostatic lipid profile. Triglycerides (TG) and esterified cholesterol (EC) decreased, free cholesterol (FC) and phospholipids (PL) increased and total cholesterol (TC) did not change. FAS, MDH and IDH activities did not vary but G6PDH decreased significantly in Cd group. Regarding TG synthesis, DGAT-1 decreased while GPAT increased and FAS, LPL and DGAT-2 remained unchanged. Regarding beta oxidation, CPT-1 increased while ACO expression decreased in Cd group. In the PL pathway, CT expression was increased. All these results would justify the decrease of TG in Cd group when compared to control. In the cholesterol metabolic pathway, HMGCoAR and SREBP-2 increased. PPAR-α increased but PPAR-γ did not change. Regarding fatty acid transporters, FAT/CD36 decreased, while E-FABP increased. AR mRNA and protein expression decreased. Ultrastructural analysis showed a decrease in lipid droplets and signs of cellular damage in the Cd group. Cadmium exposure induces important changes in prostatic lipid profile and metabolism, confirmed by the morphology analyses, which also showed signs of cellular damage. These results could be important to further understanding the complex mechanism of cadmium toxicity in prostate and in the development of better treatments for people and animals exposed to the heavy metal. Fellowship from the National Council of Scientific and Technical Investigations (CONICET) – Argentina. Career Scientific Investigator. National Council of Scientific and Technical Investigations (CONICET) – Argentina.     

Biomarkers of air pollution exposure--a study of policemen in Prague

The effect of exposure to organic compounds adsorbed onto respirable air particles (<2.5microm) on DNA adducts in lymphocytes was studied in a group of non-smoking policemen (N=109, aged 35+/-0.9 years) working in the downtown area of Prague and spending >8h daily outdoors. Personal exposure to carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) adsorbed on respirable particles was monitored in each subject for 48h before biological sampling. DNA adducts were analyzed by a (32)P-postlabelling assay, and total DNA adduct levels and B[a]P-like spots were determined. Further biomarkers included cotinine levels in urine to control for exposure to tobacco smoke, plasma levels of vitamins A, E and C and polymorphisms of metabolic genotypes (GSTM1, GSTP1, GSTT1, CYP 1A1-Msp I and Ile/Val, MTHFR, MS), DNA repair genotypes (XRCC1, hOGG1 and XPD exons 6 and 23) and the p53 gene (p53 Msp I and BstU I). All the biomarkers of exposure and effect were analyzed repeatedly during a period of one year at 2-3 month intervals (January, March, June, September 2004) to cover periods with high (winter) and low (summer) levels of air pollution. The highest personal exposure to c-PAHs was found in January (8.1+/-8.8ng/m(3)), while the other three sampling periods exhibited 3-4-fold lower c-PAH exposure. The total DNA adducts were only slightly elevated in January (2.08+/-1.60) compared to March (1.66+/-0.65), June (1.96+/-1.73) and September (1.77+/-1.77). B[a]P-like DNA adducts, however, were significantly higher in January than in the March and June sampling periods (0.26+/-0.14 vs. 0.19+/-0.12 and 0.22+/-0.13, respectively; p<0.0001 and p=0.017) indicating that c-PAH exposure probably plays a crucial role in DNA adduct formation in lymphocytes. No effect of individual metabololic or DNA repair genotypes on DNA adduct levels was observed. However, the combination of two genotypes encoding enzymes metabolizing c-PAHs - CYP 1A1 and GSTM1 - was associated with the levels of total and B[a]P-like DNA adducts under conditions of increased exposure to c-PAHs. Our study suggests that DNA adducts in the lymphocytes of subjects exposed to increased c-PAH levels are an appropriate biomarker of a biologically effective dose, directly indicating whether or not the extent of exposure to these compounds is related to an increased mutagenic and carcinogenic risk.     

镉的环境激素效应研究进展

镉属于环境内分泌干扰物,具有激素效应,可以模拟体内正常的激素水平。根据近年来关于镉的激素效应的研究报道,从镉的激素作用机理及其诱导肿瘤等方面综述了镉的激素效应。     

Effects of environmental conditions on the nitrifying population dynamics in a pilot wastewater treatment plant

The effect of environmental conditions, especially ammonium concentration, on community composition and nitrification activity of nitrifying bacterial biofilms in a pilot wastewater treatment plant was examined. A decreasing ammonium gradient was created when four aerated tanks with suspended carrier material were serially fed with wastewater. Community composition was analysed using fluorescence in situ hybridization (FISH) probes as well as partial 16S rRNA and amoA gene analysis using polymerase chain reaction-denaturating gradient gel electrophoresis (PCR-DGGE) and sequencing. Fluorescence in situ hybridization probes identified at least five ammonia-oxidizing bacterial (AOB) and two nitrite-oxidizing bacterial (NOB) populations. A change in nitrifying community was detected in the tanks, indicating that ammonium was an important structuring factor. Further, we found support for different autoecology within the Nitrosomonas oligotropha lineage, as at least one population within this lineage increased in relative abundance with ammonium concentration while another population decreased. Absolute numbers of AOB and NOB growing in biofilms on the carriers were determined and the cell specific nitrification rates calculated seemed strongly correlated to ammonium concentration. Oxygen could also be limiting in the biofilms of the first tank with high ammonium concentrations. The response of the nitrifying community to increased ammonium concentrations differed between the tanks, indicating that activity correlates with community structure.     

The distribution of cadmium within the human prostate

Five normal prostates from autopsies of humans aged 61-76 yr were divided into 2 x 24 topographically well-defined pairs of slices that were analyzed for cadmium (Cd) and examined histologically. The corresponding kidney cortex concentrations were also determined. The concentrations in ng Cd/g wet wt were in the range of 50-500 in the prostates and 8,000-39,000 in the kidneys with good mutual correlation. Large variations in Cd concentrations within the prostates were found. The concentrations were highest at the base (near the bladder) and lowest at the apex of the gland. Furthermore, large variations within horizontal layers were found, and this variation was not correlated to the histological amount of stroma or glands.     

Effects on long-term cadmium exposure on the seminal vesicles of mice.

Male CBA-mice were exposed to cadmium by subcutaneous injection of 2-2 mumol CdCl2/kg body weight for 5 days/week for 6 months. A decrease in normal (testosterone-dependent) proteinuria was shown, and morphological examination of the seminal vesicles revealed a smaller weight and size as well as histological indication of lower secretory activity of the epithelium compared to controls. The findings are consistent with a theory implying a decreased testosterone activity in cadmium-treated animals.     

Effects of cadmium on polyribosome sedimentation pattern in mouse liver.

Cadmium injected to mice provokes an acute disaggregation of hepatic polyribosomes. The effect appears within 15 min, it is maximal after 1 h and then gradually disappears. The reaggregation of polyribosomes takes place 6--12 h after injection. The disaggregation of polyribosomes is linear with log doses in a range of 7.25--20 mumol/kg CdCl2. Cycloheximide pretreatment prevents the disaggregation of polyribosomes in the livers of cadmium-treated mice.     

Effects of inhaled cadmium on breathing in the mouse

Effects of intranasally administered cadmium (3.67 micrograms Cd approximately 36.7 mg per mouse) on breathing were investigated in mice under pentobarbital anesthesia. Cd levels found in the respiratory tract were dependent on the amount administered. Cd mainly caused degeneration and desquamation of the bronchial epithelium and pulmonary congestion, while the carrier solvent had no effects. On the other hand, the carrier solvent decreased respiratory frequency and enhanced its amplitude. These effects were absent 24 h later. However, Cd strongly affected respiration; frequency and amplitude were decreased and recovery at 24 h was not complete at the higher concentrations. These effects by Cd on respiration were dependent on the concentration of administered Cd and the Cd level in lung. Therefore, these results suggest that intranasally administered Cd has inhibitory effects on mouse respiration, perhaps owing to its acute toxicity to pulmonary tissues.     

Epidemiology of prostate cancer in the mediterranean population of Croatia--a thirty-three year retrospective study

Prostate cancer is a major public health problem of the male population in all the developed countries. This non-skin cancer is the foremost one facing man today. Prostate cancer has become the second leading cause of cancer death2. In this study we investigated changes in the prostate carcinoma incidence and manifestation during a thirty-three years period. The study included 1226 cases of prostate cancer diagnosed from 1972 to 2005 in the Primorsko-Goranska County, Croatia. The age-adjusted incidence of prostate cancer increased from 1.69 per 100,000 men annually in 1972 to 137.58 per 100,000 men annually in 2005, which is an 81.4-fold increase. The percentage ofpatients with bone metastases on the first medical examination decreased from 1972 (75%) to 2005 (15%). The most of the patients with bone metastases at the first medical examination were between 30 and 50 years old. Early detection measures, such as prostate specific antigen testing and transrectal ultrasound guided prostate biopsy combined with the raised public awareness of the disease, most probably resulted in an increase of incidence.     

Factors associated with prelacteal feeding in the rural population of northwest Ethiopia: a community cross-sectional study

Background

Prelacteal feeding has continued as a deep-rooted nutritional malpractice in developing countries. Prelacteal feeding is a barrier for implementation of optimal breastfeeding practices, and increases the risk of neonatal illness and mortality. However, its determinants are not well studied, which are essential to design intervention. This study aimed to assess the prevalence and determinants of prelacteal feeding among mothers with children aged 6–24 months in the rural population of northwest Ethiopia.

Methods

A community based cross-sectional study was conducted in Dabat Health and Demographic Surveillance System site, Dabat district, northwest Ethiopia from May 01 to June 29, 2015. Eight hundred and twenty-two mother-child pairs were included in the study. A pretested and structured questionnaire was used to collect data. Multivariable logistic regression analysis was carried out to identify the determinants of prelacteal feeding.

Results

In this community, about 26.8 % of children were given prelacteal feeds. The odds of prelacteal feeding was higher among mothers with a poor knowledge of Infant and Young Child Feeding (IYCF) (Adjusted Odds Ratio [AOR]?=?3.82; 95 % Confidence Interval [CI] 2.42, 6.04), who gave birth at home (AOR?=?3.74; 95 % CI 2.12, 6.60), and who were in the lowest wealth status (AOR?=?2.11; 95 % CI 1.35, 3.31).

Conclusions

Prelacteal feeding was common in the study area, and significantly associated with a poor household wealth status, poor maternal knowledge of IYCF, and giving birth at home. Thus, emphasis should be given to improve mothers IYCF knowledge and utilization of institutional delivery. Moreover, special attention should be given to mothers with poor socio-economic status to reduce the practice of prelacteal feeding.

     

Effects of estradiol on prostate epithelial cells in the castrated rat.

There is evidence that estrogens can modulate the activity of prostate epithelial cells. To determine whether estradiol can have a direct influence on rat prostate, this study examined the effects of estradiol-17beta (E(2)) administered alone or in combination with dihydrotestosterone (DHT) to castrated rats for 3 weeks on prostate binding protein (PBP) C1 mRNA expression and androgen receptor (AR) localization. PBP C1 mRNA levels were measured by semi-quantitative in situ hybridization using a (35)S-labeled cDNA probe. In intact animals, strong hybridization signal could be observed in prostate sections after 12 hr of exposure to Kodak X-Omat films. In castrated rats, no PBP C1 mRNA could be detected even with longer exposure times, an effect that was prevented by administration of DHT. E(2) administered alone induced a detectable hybridization signal, and the concomitant administration of E(2) and DHT induced an increase in PBP C1 mRNA that significantly exceeded that obtained in animals that received only DHT. In prostate epithelial cells of intact animals, AR immunostaining was restricted to the nucleus. In castrated animals the alveoli were decreased in size and the epithelial cells were atrophied. AR staining was weak and was detected in both cytoplasm and nucleus. DHT administration completely obviated the effect of castration on epithelial cell histology and on AR immunostaining distribution and intensity. Interestingly, E(2) administration alone induced moderate hypertrophy of epithelial cells compared to the histological appearance of cells in untreated castrated rats. Moreover, in E(2)-treated animals the nuclear staining was much stronger than that detected in untreated castrated rats, whereas the cytoplasmic staining was not modified by the treatment. In animals that received both DHT and E(2), the staining was similar to that seen in DHT-treated rats. These results suggest that E(2) can influence the activity of rat prostate epithelial cells by mechanisms that remain to be fully clarified.     

Association of overtime work and hypertension in a Japanese working population: A cross-sectional study

Long working hours have been associated with an increased risk of cardiovascular disease, but its relationship with hypertension remains unclear. The objective of this study is to examine the relationship between overtime and presence of hypertension using data from a large-scale multi-company study in Japan. Participants were 52?365 workers of four companies that provided both health-checkup data and self-reported data on overtime worked. Hypertension was defined as systolic blood pressure ≥140?mmHg, diastolic blood pressure ≥90?mmHg, and/or the use of antihypertensive drug. Logistic regression analysis was performed to determine the odds ratio for hypertension for each category of overtime work (<45, 45–79, 80–99 or ≥100?h/month) with adjustments for age, sex, company, smoking status and body mass index. The prevalence of hypertension tended to decrease with increasing overtime work: 17.5, 12.0, 11.1 and 9.1% for the shortest (<45?h/month) through the longest overtime category (≥100?h/month). The age-, sex- and company-adjusted odds ratios (95% confidence interval) were 1.00 (reference), 0.81 (0.75–0.86), 0.73 (0.62–0.86), 0.58 (0.44–0.76), respectively (p for linear trend <0.001). In a sub-cohort, the inverse association remained statistically significant after an additional adjustment for other potential confounders. Results of the present large-scale study among Japanese workers suggest an inverse association between overtime work and presence of hypertension.     

Effects of soil cadmium on Pinus sylvestris L. seedlings

The effects of Cd on the growth and distribution of Cd and mineral nutrients within plant tissues were investigated for Pinus sylvestris L. seedlings grown in mineral forest soil with increasing levels of Cd addition (0–100 mg kg^–1). Approximately 20% of added Cd was found to be extractable from sandy loam forest soil. Root growth was less affected by Cd than shoot growth, which showed a significant reduction in the 100 mg Cd kg^–1 treatment. Cadmium accumulated in roots up to 325 mg kg^–1. Decreased concentrations of K in needles and Ca in stems with increasing Cd levels suggest a disturbance of mineral nutrition as a result of Cd addition.     

The effect of testosterone and cadmium on the rat lateral prostate in organ culture

Organ culture of rat lateral prostate was performed in the presence of testosterone and cadmium. Maintenance of epithelial cells did not occur even in the presence of the androgen, but basal cells were stimulated and replaced original epithelium. Testosterone alone caused a partial differentiation of these basal cells. Cadmium alone was found to enter the epithelial and basal cells and subsequently cause necrosis. The metal was subcellularly located in the nucleus and within cytoplasmic organelles. Cadmium appears to compete with zinc in cultured lateral prostate and affects the differentiation and maintenance of the epithelial growth.     

Effects of cadmium on lymphocyte activation

The effects of cadmium (Cd) on phytohemoagglutinin or phorbol myristate acetate-induced lymphocyte activation were investigated and a dose-dependent inhibition of cell proliferation was found. Kinetic studies revealed that the Cd-sensitive step is an early event of T cell stimulation. Failure of IL2 secretion and reduction of IL2 receptor expression in the Cd-treated cells are also reported. Regardless of which mechanism is responsible for Cd effects, our studies show that the inhibition of lymphocyte activation is associated with reduced [3H]phorbol dibutyrate binding to Ca2+-phospholipid-dependent protein kinase and altered breakdown of phosphatidylinositols. Thus, Cd interferes with two biochemical events which play a critical role in lymphocyte signal transduction and activation.