Vanadium inhalation effects on the corneal ciliary neurotrophic factor (CNTF): study in a murine model.

PURPOSE: Air pollution is a public health problem caused by predatory human activities and the indiscriminate burning of fossil fuels that liberate particulate matter (PM) into the atmosphere. Vanadium (V) adheres to them and reaches the bloodstream and different organs such as the eye when inhaled. Another way to reach the eye is by direct contact, and the cornea is the first layer exposed. Ciliary neurotrophic factor (CNTF) is secreted by the corneal nerves and some of its functions include self-renewal maintenance and wound healing by the activation of STAT3. Previous reports from our group indicate the activation of STAT3 after the inhalation of V, adhered to PM. OBJECTIVE: To analyse the effect of V inhalation in the expression of CNTF. Method: CD-1 male mice were exposed for 4 and 8 weeks to V inhalation. The eyes were removed, and the corneas were processed for immunohistochemistry for CNTF and analysed by densitometry. The same slides were used to evaluate histological modifications and to measure the corneas' anterior epithelial and endothelial thickness. RESULTS: A decrease in CNTF expression in the anterior epithelium in the 8th week, as well as an increase in the endothelial and corneal thickness and disarray of all the layers of the anterior epithelium. CONCLUSION: V inhalation disturbs the architecture of the cornea and modifies the presence of CNTF which might modify the renewal of the corneas after exposure to PM air pollution.

Effects of Vanadium Inhalation and Sweetened Beverage Ingestion in Mice: Morphological and Biochemical Changes in the Liver.

The aim of this report was to evaluate the morphological and biochemical changes in the liver by the inhalation of vanadium and consumption of sweetened beverages in a subchronic murine model. Forty CD-1 male mice were randomly divided into four groups: control, vanadium (V), sucrose 30% (S), and vanadium-sucrose (V + S). V was inhaled (1.4 mg/m3) for 1h, twice/week; 30% sucrose solution was given orally ad libitum. Blood samples were obtained for AST, ALT, and LDH determination. Liver samples were processed for histological and oxidative stress immunohistochemical evaluation with 4-hydroxynonenal at weeks 4 and 8 of exposure. Regarding liver function tests, a statistically significant increase (P < 0.05) was observed in groups V, S, and V + S at weeks 4 and 8 compared to the control group. A greater number of hepatocytes with meganuclei and binuclei were observed in V and V + S at week 8 compared to the other groups. Steatosis and regenerative changes were more extensive in the eighth week V + S group. 4-Hydroxynonenal immunoreactivity increased in the V + S group at both exposure times compared to the other groups; however, the increment was more evident in the V + S group at week 4 compared to the V + S group at week 8. An increase in De Ritis ratio (>1) was noticed in experimental groups at weeks 4 and 8. Findings demonstrate that in the liver, V, S, and V + S induced oxidative stress and regenerative changes that increased with the length of exposure. Results support possible potentiation of liver damage in areas with high air pollution and high-sweetened beverage consumption.

Sex differences in vanadium inhalation effects in non-ciliated bronchiolar cells.

The non-ciliated bronchiolar cell (NCBC) is responsible for the defense of the lung and responds to negative stimuli such as exposure to toxic pro-oxidant substances, which triggers the hyperproduction and hypersecretion of mucins and CC16 protein. The literature demonstrates that physiological and pathological responses in the lung can be influenced by the organism's sex. The objective of this report was to evaluate response differences to vanadium (V) inhalation in male and female CD-1 mice. Mice were exposed to V for four weeks. Hyperplasia of bronchiolar epithelium, small inflammatory foci and sloughing of the NCBC were observed, without changes between sexes and throughout the exposure time. Mucosecretory metaplasia was found in both males and females, however it was more drastic in males. The expression of CC16 increased in both sexes. This study demonstrated a different susceptibility between male and female mice exposed to V inhalation regarding mucosecretory metaplasia.

Trimethoprim-Sulfamethoxazole-associated early neutropenia in Mexican adults living with HIV: A cohort study.

INTRODUCTION: Trimethoprim/sulfamethoxazole (TMP/SMX) is the antimicrobial of first choice in the treatment and prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients, particularly in people living with human immunodeficiency virus (HIV). TMP/SMX use entails different adverse effects, and its association with early neutropenia is minimally documented. This study aimed to identify the risk of early neutropenia associated with TMP/SMX use in adults living with HIV in Mexico. METHODS: A prospective cohort study was conducted in TMP/SMX-naïve adults living with HIV admitted to a third-level hospital between August 2019 and March 2020. Socio-demographic, clinical, and laboratory data were collected. According to patients' diagnostic, if they required treatment or prophylaxis against PCP, medical staff decided to prescribe TMP/SMX, as it is the first-line treatment. The risk of TMP/SMX induced early neutropenia, as well as associated factors were analyzed through a bivariate model and a multivariate Poisson regression model. The strength of association was measured by incidence rate ratio (IRR) with 95% confidence interval. RESULTS: 57 patients were enrolled in the study, of whom 40 patients were in the TMP/SMX treatment-group for treatment or prophylaxis of PCP (204.8 person-years of observation, median 26.5 days) and 17 patients were in the non-treatment group because they did not need the drug for treatment or prophylaxis of PCP (87.0 person-years of observation, median 21 days). The incidence rate of early neutropenia in the TMP/SMX-treatment group versus non-treatment group was 7.81 and 1.15 cases per 100 person-years, respectively. After adjusting for stage 3 of HIV infection and neutrophil count <1,500 cells/mm3 at hospital admission, the current use of TMP/SMX was not associated with an increase in the incidence rate ratio of early neutropenia (adjusted IRR: 3.46; 95% CI: 0.25-47.55; p = 0.352). CONCLUSIONS: The current use of TMP/SMX in Mexican adults living with HIV was not associated with an increase in the incidence rate ratio of early neutropenia.

Claudin-6, 7, or 9 overexpression in the human gastric adenocarcinoma cell line AGS increases its invasiveness, migration, and proliferation rate.

Altered claudin expression is related to metastatic potential, poor prognosis, or tumor recurrence. We analyzed if the overexpression of claudin-6, claudin-7, or claudin-9 in AGS cells altered cell motility, invasiveness, or proliferation rate. Claudin-7, claudin-9, and claudin-6 enhanced their invasive potential by 3.4-fold, 1.6-fold, and 2.0-fold, respectively. Claudin-6 and claudin-9 enhanced cell migration, while the proliferation rate of claudin-6-, claudin-7-, and claudin-9-transfected cells increased by 12.7%, 9.0%, and 13.3%, respectively. Claudin-7 and claudin-9 overexpression increased claudin-1 and zonula occludens-1 levels. In summary, individual increased expression of claudin-6, claudin-7, or claudin-9 is sufficient to enhance tumorigenic properties of a gastric adenocarcinoma cell line.

Morphological changes in the tongue as a consequence of manganese inhalation in a murine experimental model: light and scanning electron microscopic analysis.

Air pollution by suspended particles has become a worldwide health problem. The main sources of these particles are fossils and additives combustion. Mn enters the body through inhalation, but part of the particles accesses contact with tongue's posterior surface where lingual tonsils and lingual papillae are placed. We decided to explore in a mouse model, the impact that the deposit of inhaled Mn has on the tongue's surface. Atrophy of the lingual tonsil, filiform papillae, as well as the swelling of taste buds in fungiform papillae, were the predominant changes. Ferropenic anemia is associated with the changes described and could be related to the interference of Mn in iron metabolism and riboflavin absorption. More research should be done to explore the participation of suspended particles trapped in the oral cavity in toxicology of Mn or other inhaled pollutants.

Ultrastructural findings in murine seminiferous tubules as a consequence of subchronic vanadium pentoxide inhalation.

Vanadium (V) is a transition metal emitted to the atmosphere during the combustion of fossil fuels. Its current status as an atmospheric pollutant increases the need for information about the effects that this element might have on the reproductive health of exposed populations. The present study investigated changes in testicular ultrastructure following inhalation exposure of male mice to V (as vanadium pentoxide). Tissue V level was constant during the 12-week time period. We observed necrosis of spermatogonium, spermatocytes and Sertoli cells, as well as pseudo-nuclear inclusion and disruption of cellular junctions. Our findings stressed the importance of the hemato-testicular barrier in supporting the function of Sertoli cells and suggest as a possible target of V, tight junction proteins. Further analysis is needed in order to identify the role that reactive oxidative species (ROS) might have on these cellular junctions, and if a specific protein is the target of its toxic effects. The relevance of this report concerns the impact that metal air pollution could have on male fertility in dense cities with vehicular traffic problems.

Sex differences in bronchiolar epithelium response after the inhalation of lead acetate (Pb).

In order to identify if there were sex differences in lead (Pb) lung concentrations and in bronchiolar response after its inhalation, a mice inhalation model was conducted. Sixty CD-1 adult mice from each sex inhaled separately, lead acetate 0.1 M for 1 h, thrice weekly during 15 days. Animals were evaluated for Pb-lung concentrations by atomic absorption spectrometry and for morphological evaluation by scanning electron microscopy (SEM). Higher Pb-lung concentrations were determined in females, however, more cell damage was found in males, finding that correlated with an increased loss of the nonciliated bronchiolar cells (NCBC) more sloughing and necrosis. Differences in particle clearance, oxidative stress handling, cytokines pathway activation and cytochrome P450 enzymes activity, all influenced by sex hormones, might be a possible explanation for our findings. The relevance of further studies in this field is stressed, as well as its relation to the different development expected for each sex in disease evolution, possible complications and treatment response.

Single-cell gel electrophoresis assay of nasal epithelium and leukocytes from asthmatic and nonasthmatic subjects in Mexico City.

The prevalence of asthma--a chronic inflammatory respiratory disease--is increasing worldwide. One hypothesis suggests that this trend is related to enhanced exposure to air pollutants. Chronic inflammation generates oxidative stress, and cells involved in an allergic reaction are capable of producing reactive oxygen species that may predispose asthmatics to increased deoxyribonucleic acid (DNA) damage. The authors estimated DNA strand breaks by use of single-cell gel electrophoresis assay on 2 different cell types (i.e., nasal epithelial cells and leukocytes) sampled from asthmatic and nonasthmatic medical students in Mexico City. The authors found that asthmatic subjects had more DNA breaks in their nasal epithelial cells than did their nonasthmatic counterparts. In contrast, asthmatic subjects had less damage in their leukocytes than did nonasthmatic individuals. These findings suggest that the hyperreactivity of the nasal epithelium prevents systemic effects from air pollutants, as reflected by less DNA injury to leukocytes of the asthmatic group. Asthmatic's nasal epithelial cells were more sensitive to DNA damage than were those of nonasthmatics--perhaps as a consequence of increased fragility induced either by air pollution or by a chronic inflammatory response.

Vanadium in ambient air: concentrations in lung tissue from autopsies of Mexico City residents in the 1960s and 1990s.

Vanadium concentrations in lung tissue were determined by atomic absorption spectrometry from autopsy specimens taken from residents of Mexico City during the 1960s and 1990s (20 males and 19 females, and 30 males and 18 females, respectively). Samples from the 1990s had significantly increased mean vanadium concentrations (mean +/- standard deviation: 1.36 +/- 0.08), compared with those from the 1960s (1.04 +/- 0.05). Concentrations were not correlated with gender, smoking habit, age, cause of death, or occupation. These findings suggest that vanadium in ambient air is increasing and it represents a potential health hazard for Mexico City residents. Air pollution monitoring efforts should include vanadium concentrations in suspended particles to follow-up the findings reported herein. Researchers need to acquire a better knowledge of the levels of airborne vanadium exposure at which risk to human health occurs.

Estrogen receptor beta and CXCR4/CXCL12 expression: differences by sex and hormonal status in lung adenocarcinoma.

BACKGROUND AND AIMS: Studies have reported differences in lung cancer behavior between sex and hormonal status that suggest a role of estrogens and estrogen receptor beta (ERß) in lung carcinogenesis. In some types of hormone-dependent cancer, estrogens may regulate CXCL12/CXCR4 expression through ERß signaling. High expression of CXCL12/CXCR4 is associated with poor prognosis in lung cancer because it promotes tumor growth and metastasis. Therefore, in this study we investigated whether lung adenocarcinoma tissues from pre- and postmenopausal women and from men exhibit different ERß, CXCR4/CXCL12 expression and whether this expression is associated with clinicopathological features. METHODS: Sixty primary tumor samples of lung adenocarcinoma from pre- and postmenopausal women and from men were collected for this study. Thirty samples of healthy lung tissue adjacent to the tumor site were used as controls. ERß and CXCL12/CXCR4 expression was analyzed by immunohistochemistry. Expression of these proteins was measured by digital image software and compared between sex and hormonal status. RESULTS: Lung adenocarcinomas overexpressed ERß, CXCR4 and CXCL12 compared to normal lung. Moreover, lung adenocarcinomas from premenopausal women exhibited higher signals for ERß, CXCL12 and CXCR4 compared to postmenopausal women and to men, who showed lower signals for these proteins. A multivariate analysis revealed a strong association between the immunoreactivity level of ERß, CXCL12/CXCR4 and both sex and hormonal status, but not with tumor stage and smoking. CONCLUSION: These results demonstrated that ERß and CXCL12/CXCR4 expression in lung adenocarcinoma depends on sex and hormonal status, which may partly explain the sex and hormonal differences in lung cancer behavior.

The effect of vanadium on platelet function.

Vanadium pentoxide (V(2)O(5)) inhalation effect on platelet function in mice was explored, as well as the in vitro effect on human platelets. Mouse blood samples were collected and processed for aggregometry and flow cytometry to assess the presence of P-selectin and monocyte-platelet conjugates. Simultaneously, human platelets were processed for aggregometry(.) The mouse results showed platelet aggregation inhibition in platelet-rich-plasma (PRP) at four-week exposure time, and normality returned at eight weeks of exposure, remaining unchanged after the exposure was discontinued after four weeks. This platelet aggregation inhibition effect was reinforced with the in vitro assay. In addition, P-selectin preserved their values during the exposure, until the exposure was discontinued during four weeks, when this activation marker increased. We conclude that vanadium affects platelet function, but further studies are required to evaluate its effect on other components of the hemostatic system.

Estrógenos y su influencia en el cáncer pulmonar / The influence of estrogens in lung cancer

Resumen Actualmente, el cáncer pulmonar es un problema de salud importante a nivel mundial porque presenta una alta incidencia y mortalidad tanto en hombres como en mujeres. Su forma más común es el adenocarcinoma (ADC), que es una entidad patológica interesante ya que de todas las formas de cáncer pulmonar, es la que se asocia menos con el tabaquismo y un porcentaje importante de pacientes con adenocarcinoma son no fumadores. De modo que otros factores como la exposición al humo de leña, a los contaminantes del aire, la historia familiar de cáncer, entre otros, son importantes para el desarrollo del ADC pulmonar. Actualmente el ADC pulmonar es la principal forma de cáncer pulmonar en las mujeres y se ha reportado que las mujeres premenopáusicas presentan peor pronóstico y los tumores son más agresivos cuando se comparan con los hombres y las mujeres posmenopáusicas. Estos datos han sugerido el papel de los estrógenos en el cáncer pulmonar, principalmente en el ADC. Aunque existe vasta evidencia epidemiológica que demuestra esta relación, hay controversia en cuanto al papel de los estrógenos en esta patología. De igual manera no hay una opinión generalizada sobre los mecanismos por los cuales los estrógenos podrían favorecer la carcinogénesis. Sin embargo, cada vez es más clara la importancia de éstas hormonas en la carcinogénesis pulmonar. En esta revisión se muestran estos datos y se discute la relevancia de los estrógenos en el cáncer pulmonar, una patología cuya dependencia hormonal es cada vez más clara.

Abstract Lung cancer is currently a worldwide health issue because of the mortality and high incidence of this pathology in both men and women. The most common form of lung cancer is adenocarcinoma (ADC); It is an interesting disease entity because among every type of lung cancer it has the lower association with smoking and a significant percentage of patients with adenocarcinoma are not smokers. Hence other factors such as exposure to wood-smoke, air pollutants, family history of cancer, among others, are important in the development of lung ADC. Nowadays, lung ADC is the main form of lung cancer in women and reports show that premenopausal women have the worse prognosis and have more aggressive tumors compared to men and postmenopausal women. These data suggests that estrogens have a particular role in lung cancer physiopathology mainly in ADC. Although there is sufficient epidemiological evidence that indicates a relationship between sexual hormones and lung cancer, the role of estrogens in this pathology is still controversial. Furthermore there is no general consent regarding the known mechanisms by which these hormones could promote carcinogenesis and because the scarce information about the implication of these hormones in lung carcinogenesis more studies are needed. In this review we discuss the role and relevance of estrogens in lung cancer, a pathology whose hormonal dependency is becoming clearer.

Lead blood concentrations and renal function evaluation: study in an exposed Mexican population.

The relation of blood Pb concentrations and renal dysfunction has been reported in association with interstitial fibrosis, tubular atrophy, and decreased glomerular filtration. In this report information about blood Pb concentrations and renal function tests in a population from Oaxaca, Mexico is analyzed. The main changes found were that males had higher blood Pb concentrations than females (P<0.0012); the leading variables associated with this were occupation (glazed pottery workers, P=0.0001) and the use of glazed pottery for preparing meals (P=0.0000). Variables that better explain uric acid variability were blood Pb concentrations, sex, weight, and height (r2=0.23). Hyperuricemia was associated with blood Pb concentrations above 40 microg/dL (OR=1.74, 95% CI, 1.12-2.61). SCr was associated with sex, age, and blood Pb, with coefficient r2=0.12. Our findings might be related to inadequate control of oven emissions, a situation that will require further analysis and the implementation of preventive measurements for the nonoccupational exposed population.

Nasal cytology and genotoxic damage in nasal epithelium and leukocytes: asthmatics versus nonasthmatics.

BACKGROUND: The best example of a chronic inflammatory respiratory disease is asthma, a disease which has an increasing prevalence worldwide. This chronic inflammation is also related to the generation of oxidative stress since the cells involved in the allergic reaction are capable of producing reactive oxygen species (ROS), and this might predispose asthmatics to increased genotoxic damage. METHODS: A respiratory symptomatology questionnaire was self-applied by asthmatic and nonasthmatic students. A single cell gel electrophoresis assay in two different cell types (nasal epithelial cells and leukocytes) was performed, and the cytology of the nasal smears stained with HE was evaluated. RESULTS: Both groups reported having a runny nose. Asthmatics had greater DNA damage in the nasal epithelial cells in contrast to nonasthmatics. In leukocytes no statistical significance in DNA damage was identified. Metaplasia was evident in asthmatics that also showed eosinophils and neutrophils as well as goblet cells and mucus at a higher frequency compared with nonasthmatics. CONCLUSIONS: Nasal symptoms did not correlate with genotoxic damage, since they were reported in both groups. Nasal epithelial cells of asthmatics are more sensitive to genotoxic damage, and chronic inflammatory response. Also the activity of eosinophils might mediate the DNA damage through the generation of ROS.