Interaction effects of MTHFR C677T and A1298C polymorphisms with maternal glycated haemoglobin levels on adverse birth outcomes.

AIMS: The role of maternal genetic factors in the association between high glycated haemoglobin (HbA1c) levels and adverse birth outcomes remains unclear. MATERIALS AND METHODS: In this study, the maternal HbA1c levels of 5108 normoglycemic pregnant women in China were measured, and A1298C and C677T polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene were genotyped. RESULTS: Elevated HbA1c levels during the second trimester were associated with increased risks of macrosomia, large-for-gestational age (LGA), preterm birth (PTB), and reduced gestational age (p < 0.05). Pregnant women with MTHFR A1298C AA or C677T CT + TT genotypes were susceptible to adverse pregnancy outcomes related to HbA1c levels. Among pregnant women with the A1298C AA genotype, each standard deviation (SD) increase in HbA1c levels increased the risk of PTB by 1.32-times and reduced the gestational age by 0.11 weeks (p < 0.05). For MTHFR C677T CC + TT genotype carriers, higher HbA1c levels were associated with 1.49-, 1.24-, and 1.23-times increased risks of macrosomia, LGA, and PTB, respectively (p < 0.05). A U-shaped curve for PTB risk in relation to HbA1c levels was observed among the C677T CC + TT participants, with a cut-off value of 4.58%. Among subjects with the A1298C AA genotype combined with the C677T CT + TT genotype, each SD increase in HbA1c levels was associated with 1.40 and 1.37-times increased risks of LGA and PTB, respectively. CONCLUSIONS: Our findings highlight the importance of glycaemic control during pregnancy and the potential impact of genetic factors on birth outcomes. However, further large-scale studies are required to confirm these findings.

Blood-cerebrospinal fluid barrier permeability of metals/metalloids and its determinants in pediatric patients.

Concerns regarding adverse effects of metal/metalloids exposure on brain development and neurological disorders among children are increasing. However, the transport patterns of metals/metalloids across the blood-cerebrospinal fluid barrier (BCSFB) need to be clarified in children. A total of 99 Chinese pediatric patients were enrolled from February 2020 to August 2021, with a median age of 6.76 months. We detected 16 metal/metalloid levels in matched serum and cerebrospinal fluid (CSF) samples using inductively coupled plasma mass spectrometry. The BCSFB permeability of metals/metalloids were estimated and the potential effects of biomedical parameters were explored. Most metals/metalloids were detectable among > 80.0% of CSF samples. Significant correlations were observed between strontium (Sr, r = 0.46), molybdenum (Mo, r = 0.50), and cadmium (Cd, r = 0.24) concentrations in serum and CSF (P < 0.05). Ratios of metal/metalloid levels in CSF to serum (Rmetal) ranged from 0.02 to 0.74, and hazardous metals/metalloids including arsenic (As), Cd, lead (Pb), thallium (Tl), and manganese (Mn) showed high transfer efficiencies across the BCSFB (Rmetals > 0.5). With the adjustment of age and sex, albumin, ß2-microglobulin, and total protein levels in CSF were positively associated with copper (Cu) permeability (FDR-adjusted P < 0.05), while glucose in CSF was negatively correlated with calcium (Ca), Cu, Sr, and Mo BCSFB permeability (FDR-adjusted P < 0.05). Q-Alb promoted Cu permeability across the BCSFB (FDR-adjusted P < 0.001), while C-reactive protein levels in serum were positively associated with selenium (Se) permeability (FDR-adjusted P = 0.046). For the first time, our findings provided data for the BCSFB permeability of 16 metals/metalloids in children, and indicated that some biomedical parameters could influence the transformation of metals/metalloids from serum to CSF. Metals/metalloids with strong BCSFB permeability warrant attention for their potential neurotoxicity.

Maternal pre-pregnancy BMI, MTHFR polymorphisms, and the risk of adverse pregnancy outcomes in pregnant women from South China: a retrospective cohort study.

BACKGROUND: Increasing evidence suggests an association between maternal pre-pregnancy body mass index (pre-BMI) and adverse pregnancy outcomes. However, the effects of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on these relationships require further investigation. This study aimed to investigate whether the relationship between pre-BMI and the risk of adverse pregnancy outcomes was influenced by MTHFR gene polymorphisms. METHODS: A total of 5614 mother-fetus pairs were included in the study. The odds ratios (OR) of adverse pregnancy complications, including gestational diabetes mellitus (GDM), gestational hypertension (GHT), cesarean delivery (CS), and premature rupture of membranes (PROM), were estimated using adjusted logistic regression models and subgroup analysis. RESULTS: Pregnant women with higher pre-BMI values were positively related to the risk of GDM, GHT, and CS. In the subgroup analysis, underweight BMI was associated with a decreased risk of CS and GDM in pregnant women with the MTHFR A1298C AA or C677T CC genotype, while overweight/obese BMI was associated with an increased risk of GDM and CS in different MTHFR variants. Moreover, pregnant women with MTHFR A1298C AC + CC or C667T CC were found to have an increased risk of GHT in the MTHFR A1298C AA or C667T CT + TT genotype. A remarkable association was observed between the obesity group with MTHFR A1298C AC + CC (OR = 6.49, CI: 2.67-15.79) and the overweight group with the C667T CC genotype (OR = 4.72, CI: 2.13-10.45). CONCLUSIONS: MTHFR gene polymorphisms exert a modifying effect on the association between maternal pre-BMI and the risk of GHT, CS, and GDM. Pregnant women with a high pre-BMI with specific MTHFR genotypes should be considered for GHT development.

Polymorphisms in gene MTHFR modify the association between gestational weight gain and adverse birth outcomes.

Evidence suggests a potential relationship between gestational weight gain (GWG) and adverse birth outcomes. However, the role of maternal genetic polymorphisms remains unclear. This study was conducted to investigate whether the relationship of GWG with risk of adverse birth outcomes was modified by methylenetetrahydrofolate reductase (MTHFR) polymorphisms. A total of 2,967 Chinese pregnant women were included and divided into insufficient, sufficient, and excessive groups based on the Institute of Medicine (IOM) criteria. Polymorphisms of C677T and A1298C in gene MTHFR were genotyped. Multivariable logistic regression models were introduced after controlling major confounders. Excessive GWG was found to increase the odds ratio (OR) for macrosomia [OR = 3.47, 95% confidence interval (CI): 1.86-6.48] and large-for-gestational age (LGA, OR = 3.25, 95% CI: 2.23-4.74), and decreased the OR for small-for-gestational age (SGA, OR = 0.60, 95% CI: 0.45-0.79). Pregnant women with insufficient GWG had a higher frequency of SGA (OR = 1.68, 95% CI: 1.32-2.13) and a lower rate of LGA (OR = 0.51, 95% CI: 0.27-0.96). Interestingly, significant associations of GWG categories in relation to low birth weight (LBW), macrosomia, and SGA were only suggested among pregnant women with MTHFR A1298C AA genotype. Among pregnant women with insufficient GWG group, an increased risk of 3.96 (95% CI: 1.57-10.01) for LBW was observed among subjects with the A1298C AA genotype, compared to the AC+CC genotype group. GWG categories are closely related to LBW, macrosomia, SGA and LGA, and the associations were modified by the polymorphism of MTHFR A1298C.

Maternal essential metals, thyroid hormones, and fetal growth: Association and mediation analyses in Chinese pregnant women.

BACKGROUND: Essential metals play critical roles in fetal growth and development, but results from human studies are inconsistent. Additionally, whether maternal thyroid hormone (TH) levels mediate the associations between essential metals and fetal growth remains unknown. METHODS: Data for analysis were extracted from the Information System of Guangdong Women and Children Hospital between January 2017 and December 2019. Maternal levels of essential metals [copper (Cu), zinc (Zn), magnesium (Mg), and iron (Fe)] and THs were measured at the second trimester. Multivariate linear models were introduced to evaluate the potential associations between maternal essential metals, thyroid functions, and fetal growth, and the possible mediation effects of thyroid functions were explored in the median analyses. RESULTS: A total of 4186 mother-infant pairs were included in the present study. Maternal Fe levels were found to significantly increase birth weight in 272.91 g (95 % CI: 15.59, 530.22) among anemia group. Maternal Cu levels were positively associated with increased free triiodothyronine/free thyroxine ratio (FT3/FT4). Negative associations of Fe and Mg levels with thyroid-stimulating hormone (TSH) concentrations were observed, accompanied with the positive associations in relation to FT3, FT4 and FT3/FT4 ratio. Mediation analyses suggested that 72.01 % of the associations between Fe levels and birth length might be mediated by FT3 levels. Additionally, 25.85 % of the Cu-birth length association and 44.53 % of the Fe-birth length association could be explained by FT3/FT4 ratio. CONCLUSION: Our findings suggest that maternal Cu, Mg, and Fe levels can alter TH concentrations, and maternal FT3 and FT3/FT4 ratio might be potential mediators on the developmental effects of Cu and Fe levels.

Lab-on-Membrane Platform Coupled with Paper Spray Ionization for Analysis of Prostate-Specific Antigen in Clinical Settings.

The analysis of protein antigens as biomarkers in clinical samples is particularly helpful for the early diagnosis of diseases. However, this is difficult to accomplish owing to the presence of the antigens in trace amounts as well as the complexity of the matrixes in clinical samples. In this study, a lab-on-membrane platform that can be combined with paper spray ionization mass spectrometry was developed for the in situ high-throughput sensitive detection of the prostate-specific antigen (PSA). The sensitivity of the proposed platform was enhanced via two strategies: (1) the synthesis of a biotin-streptavidin scaffold caused an increase in the capturing efficiency of PSA by a factor of 5 and (2) the immobilization of a large number of mass tag molecules on the gold nanoparticles allowed for the amplification of the mass spectrometry signals. The limit of detection was approximately 3.0 pg mL-1. The selectivity to PSA was guaranteed by using an antibody-aptamer pairing sandwich immunoassay, and PSA detection was unaffected even when other protein antigens (carcinoembryonic antigen and carbohydrate antigen 125) were present. The modified membranes maintained their performance for at least 30 days when stored at 4 °C. Finally, analysis of human serum samples confirmed that the PSA concentration as determined using the proposed platform was consistent with that determined with a conventional chemiluminescent immunoassay. Thus, this PSA analyzing platform is suitable for prostate cancer diagnosis in clinical settings.

Rapid visual detection of dengue virus by combining reverse transcription recombinase-aided amplification with lateral-flow dipstick assay.

OBJECTIVES: Dengue caused by infection with the dengue virus (DENV) is endemic in the tropical and subtropical regions of the world and of greatest public health concern. With more large outbreaks in rural areas, the purpose of this study was to develop a point-of-care test using recombinase-aided amplification and lateral-flow dipsticks for rapidly detecting DENV in low-resource settings. METHODS: The primers for the recombinase-aided amplification (RAA) assay were designed based on 3' UTR of the DENV genome and screened. The RAA temperature, time and the concentration of primers were then optimized, as well as the lateral-flow dipstick assay (LFD) time. Finally, the diagnostic performance of the reverse transcription (RT)-RAA-LFD assay was evaluated using blood samples from 247 patients who were clinically suspected to be infected with DENV. RESULTS: The RAA primer pair F1/R2 was the optimal combination for detecting DENV. The RT-RAA was performed in an incubator block at 37°C for 20minutes, and the amplicons were visible in the flow dipsticks from a naked eye within 3minutes. The detection limit of the developed RT-RAA-LFD assay was 10 copies/µL with high specificity for DENV. Compared with commercial reverse transcription quantitative PCR assay, the kappa value of RT-RAA-LFD in the 247 clinical samples was 0.957. CONCLUSIONS: In this study, a rapid and visual point-of-care test based on RT-RAA and LFD assay was developed. It was found to be suitable for reliable detection of DENV in low-resource settings with limited laboratory capabilities and optimal storage conditions.

Association between phthalate exposure and asthma risk: A meta-analysis of observational studies.

BACKGROUND: Phthalates are ubiquitously found in numerous environments and have been related to a variety of adverse health effects. Previous studies have suggested that phthalate exposure is associated with asthma risk in humans; however, such findings are inconsistent. METHODS: The aim of the present meta-analysis was to clarify the association between phthalate exposure and asthma risk. A literature search was conducted using PubMed, EMBASE and Web of Science for relevant studies published up to January 5, 2020. Fixed-effects or random-effects models were applied to combine the results, and several subgroup analyses were used to explore the sources of heterogeneity. RESULTS: A total of 14 studies containing more than 14,000 participants were included in the present study. A positive, significant association between mono-benzyl phthalate (MBzP) levels and asthma risk was found, and the overall odds ratio (OR) was 1.17 (95% confidence interval [CI]: 1.06-1.28, P-value for overall effect [Pz] = 0.001), with a low heterogeneity (P-value for heterogeneity [Phet] = 0.193, I2 = 23.6%). The pooled ORs for mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) concentrations were 1.13 (95% CI: 1.03-1.24, Pz = 0.011) and 1.20 (95% CI: 1.00-1.42, Pz = 0.045), respectively. Children with high levels of MBzP or mono-(carboxynonyl) phthalate (MCNP) were suggested to have increased odds of asthma compared to older populations. In the subgroup analysis by study location, an increased risk for asthma in relation to levels of the sum of di-2-ethylhexyl phthalate (ΣDEHP) was observed in European studies (OR = 1.16, 95% CI: 1.00-1.34, Pz = 0.048) compared to Asia and North America. CONCLUSIONS: Urinary levels of MBzP, MEHHP, MECPP, MCNP, and DEHP were positively related to asthma risk. No significant association was observed for the other phthalate metabolites in relation to asthma risk. Further research is needed to verify these findings and shed light on the molecular mechanism by which phthalates are associated with asthma.

Pulmonary hypofunction due to calcium carbonate nanomaterial exposure in occupational workers: a cross-sectional study.

Calcium carbonate nanomaterials (nano-CaCO3) are widely used in both manufacturing and consumer products, but their potential health hazards remain unclear. The objective of this study was to survey workplace exposure levels and health effects of workers exposed to nano-CaCO3. Personal and area sampling, as well as real-time and dust monitoring, were performed to characterize mass exposure, particle size distribution, and particle number exposure. A total of 56 workers (28 exposed workers and 28 unexposed controls) were studied in a cross-sectional study. They completed physical examinations, spirometry, and digital radiography. The results showed that the gravimetric nano-CaCO3 concentration was 5.264 ± 6.987 mg/m3 (0.037-22.192 mg/m3) at the workplace, and 3.577 ± 2.065 mg/m3 (2.042-8.161 mg/m3) in the breathing zone of the exposed workers. The particle number concentrations ranged from 8193 to 39 621 particles/cm3 with a size range of 30-150 nm. The process of packing had the highest gravimetric and particle number concentrations. The particle number concentration positively correlated with gravimetric concentrations of nano-CaCO3. The levels of hemoglobin, creatine phosphokinase (CK), lactate dehydrogenase, and high-density lipoprotein cholesterol (HDL-C) in the nano-CaCO3 exposure group increased significantly, but the white blood cell count (WBC), Complement 3 (C3), total protein (TP), uric acid, and creatinine (CREA) all decreased significantly. The prevalence rate of pulmonary hypofunction was significantly higher (p = 0.037), and the levels of vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC, peak expiratory flow and forced expiratory flow 25% (FEF 25%), FEF 25-75% were negatively correlated with gravimetric concentrations of nano-CaCO3 (p < 0.05). Logistic analysis showed that nano-CaCO3 exposure level was associated with pulmonary hypofunction (p = 0.005). Meanwhile, a dose-effect relationship was found between the accumulated gravimetric concentrations of nano-CaCO3 and the prevalence rate of pulmonary hypofunction (p = 0.048). In conclusion, long-term and high-level nano-CaCO3 exposure can induce pulmonary hypofunction in workers. Thus, lung function examination is suggested for occupational populations with nano-CaCO3 exposure. Furthermore, future health protection efforts should focus on senior workers with accumulation effects of nano-CaCO3 exposure.

Mobilization and removing of cadmium from kidney by GMDTC utilizing renal glucose reabsorption pathway.

Chronic exposure to cadmium compounds (Cd(2+)) is one of the major public health problems facing humans in the 21st century. Cd(2+) in the human body accumulates primarily in the kidneys which leads to renal dysfunction and other adverse health effects. Efforts to find a safe and effective drug for removing Cd(2+) from the kidneys have largely failed. We developed and synthesized a new chemical, sodium (S)-2-(dithiocarboxylato((2S,3R,4R,5R)-2,3,4,5,6 pentahydroxyhexyl)amino)-4-(methylthio) butanoate (GMDTC). Here we report that GMDTC has a very low toxicity with an acute lethal dose (LD50) of more than 10,000mg/kg or 5000mg/kg body weight, respectively, via oral or intraperitoneal injection in mice and rats. In in vivo settings, up to 94% of Cd(2+) deposited in the kidneys of Cd(2+)-laden rabbits was removed and excreted via urine following a safe dose of GMDTC treatment for four weeks, and renal Cd(2+) level was reduced from 12.9µg/g to 1.3µg/g kidney weight. We observed similar results in the mouse and rat studies. Further, we demonstrated both in in vitro and in animal studies that the mechanism of transporting GMDTC and GMDTC-Cd complex into and out of renal tubular cells is likely assisted by two glucose transporters, sodium glucose cotransporter 2 (SGLT2) and glucose transporter 2 (GLUT2). Collectively, our study reports that GMDTC is safe and highly efficient in removing deposited Cd(2+) from kidneys assisted by renal glucose reabsorption system, suggesting that GMDTC may be the long-pursued agent used for preventive and therapeutic purposes for both acute and chronic Cd(2+) exposure.

Chronic trimethyltin chloride exposure and the development of kidney stones in rats.

We recently reported that occupational exposure to trimethyltin (TMT) is a risk factor for developing kidney stones. To further examine the association between TMT exposure and the formation of kidney stones, we conducted a 180-day animal study and exposed the randomly grouped Sprague-Dawley (SD) rats to TMT in the drinking water at doses of 0, 8.2, 32.8 and 131.3 µg kg(-1) day(-1). Transient behavioral changes were observed in the high-dose group during the first 2 weeks of exposure. TMT exposure led to a significant dose-dependent inhibition of renal H(+)/K(+)-ATPase and an increase in urinary pH. In comparison to no kidney stones being identified in the control and the lowest dose group, 1 rat in the 32.8 µg kg(-1) day(-1) dose group and 3 out of 9 rats in the 131.3 µg kg(-1) day(-1) dose group were found to have stones in the kidney/urinary tract. Pathological analysis showed that more wide spread calcium disposition was observed in kidneys of rats with TMT exposure compared with the rats in the control group. However, X-ray diffraction (XRD) analysis found that the kidney stones were mainly composed of struvite with the formula: NH4MgPO4 6H2O, while calcium-containing components were also detected. Together, this study further demonstrates through animal studies that chronic exposure to a relatively low level of TMT induces nephrotoxicity and increases the risk for developing kidney stones.

[Study on the solid sorbent tube for capturing mercury in the workplace air and determination by cold vapor atomic absorption spectrometry].

A new KMnO4-MnO2 solid multisorbent tube for capturing mercury in workplace air was developed. Experimental conditions for solid multisorbent tube, efficiency of sampling, desorption efficiency and stability were studied. Mercury and its compounds in air were captured by solid KMnO4-MnO2 sorbent filled tube and desorbed with 0. 90 mol L-1 sulfuric acid solution. Mercury and its compounds were quantitatively analyzed according to the method of GBZ/T 160. 14-2004 cold vapor atomic absorption spectrometry. The linear range of the proposed method was 0. 000 2-0. 015 0 mg L-1 with r=0. 999 1, the average efficiency of sampling was 99. 9%-100. 0% in the concentration range of 0. 001-2. 820 mg m-3 , and the breakthrough capacity was more than 505.4 microg for 300 mg KMnO4-MnO2 solid multisorbent, the average recovery rate was 96. 4% approximately103. 8%, the intra-day and inter-day precision was 3. 0% approximately 3. 3% and 3. 5% approximately 5. 2% respectively, the limit of detection was 0. 0013 mg m-3 (7. 5 L of air ) and 0. 000 6 mg m-3 (96 L of air), after sampling, and the solid multisorbent tube could be kept at least 30 d at room temperature without significant loss. The present method was simple and suitable for capturing mercury and its compounds in the workplace air and ambient air. The solid multisorbent tube was useful for personal sampling and time weighted average sampling.

Magnetic single-walled carbon nanotubes-dispersive solid-phase extraction method combined with liquid chromatography-tandem mass spectrometry for the determination of paraquat in urine.

In this study, magnetic single-walled carbon nanotubes (MSWCNTs) were prepared by impregnating magnetic Fe3O4 nanoparticles onto the surfaces of carboxylic single-walled carbon nanotubes based on electrostatic interactions. The prepared MSWCNTs were used as the adsorbent for the dispersive solid-phase extraction (DSPE) of paraquat from human urine. After adsorption, the paraquat was quantitatively desorbed with 5%TFA in acetonitrile and determined by HPLC-MS. Extraction parameters such as the type of CNT adsorbent, extraction time, sample volume, wash solvent, and the type and volume of desorption solvent were optimized to obtain high DSPE recoveries and extraction efficiencies. Under the optimized conditions, the calibration curve was linear in the range 3.75-375.0 µg/L with a correlation coefficient of 0.999 45. The LOD (S/N=3) and LOQ (S/N=10) were 0.94 and 2.82 µg/L, respectively. The recoveries ranged from 92.89 to 108.9% for spiked real urine samples with RSDs below 3.21%. Finally, the new method was successfully used to determine paraquat in urine samples of suspected paraquat poisoning patients. The MSWCNTs exhibited suitable properties and a high adsorption capacity for the extraction of paraquat.

Occupational exposure to formaldehyde and alterations in lymphocyte subsets.

BACKGROUND: Formaldehyde is used in many occupational settings, most notably in manufacturing, health care, and embalming. Formaldehyde has been classified as a human carcinogen, but its mechanism of action remains uncertain. METHODS: We carried out a cross-sectional study of 43 formaldehyde-exposed workers and 51 unexposed age and sex-matched controls in Guangdong, China to study formaldehyde's early biologic effects. To follow up our previous report that the total lymphocyte count was decreased in formaldehyde-exposed workers compared with controls, we evaluated each major lymphocyte subset (i.e., CD4(+) T cells, CD8(+) T cells, natural killer [NK] cells, and B cells) and T cell lymphocyte subset (CD4(+) naïve and memory T cells, CD8(+) naïve and memory T cells, and regulatory T cells). Linear regression of each subset was used to test for differences between exposed workers and controls, adjusting for potential confounders. RESULTS: Total NK cell and T cell counts were about 24% (P = 0.037) and 16% (P = 0.0042) lower, respectively, among exposed workers. Among certain T cell subsets, decreased counts among exposed workers were observed for CD8(+) T cells (P = 0.026), CD8(+) effector memory T cells (P = 0.018), and regulatory T cells (CD4(+) FoxP3(+) : P = 0.04; CD25(+) FoxP3(+) : P = 0.008). CONCLUSIONS: Formaldehyde-exposed workers experienced decreased counts of NK cells, regulatory T cells, and CD8(+) effector memory T cells; however, due to the small sample size; these findings need to be confirmed in larger studies.

Synthesis and characterization of Gd@C82-PVK and C60-PVK--a kind of fullerene-grafted polymer.

Different fullerene-grafted poly(N-vinylcarbazole) was synthesized by free radical polymerization and the influence of the amount of initiator, the reaction time and the reaction temperature on the polymerization was studied. Metallofullerene-grafted polymer (Gd@C82-PVK) was firstly synthesized and characterized by GPC, UV-vis, FTIR, DSC, XPS. The results demonstrated that the fullerenes had chemically combined with PVK. Fluorescence spectra suggested that the grafted fullerenes had certain influence on the fluorescence properties of the polymer. This is due to the better electron-attractive ability of fullerenes, which contributed a lot to form the electron donor-acceptor systems in fullerene-grafted poly(N-vinylcarbazole). Potential applications of this kind of materials in optical and memory devices were expected.

Mechanism underlying hypokalemia induced by trimethyltin chloride: Inhibition of H+/K+-ATPase in renal intercalated cells.

Trimethyltin chloride (TMT), a byproduct of plastic stabilizers, has caused 67 poisoning accidents in the world; more than 98% (1814/1849) of the affected patients since 1998 have been in China. As a long-established toxic chemical, TMT severely affects the limbic system and the cerebellum; however, its relationship with hypokalemia, a condition observed in the majority of the cases in the last decade, remains elusive. To understand the mechanism underlying hypokalemia induced by TMT, Sprague-Dawley (SD) rats were administered TMT to determine the relationship between H(+)/K(+)-ATPase activity and the blood and urine K(+) concentration and pH, respectively. H(+)/K(+)-ATPase protein and mRNA were observed too. In vitro changes to intracellular pH, K(+) channels in renal cells were measured. The results showed that TMT increased potassium leakage from the kidney, raised urine pH, and inhibited H(+)/K(+)-ATPase activity both in vitro and in vivo. In the tested animals, H(+)/K(+)-ATPase activity was positively correlated with the decrease of plasma K(+) and blood pH but was negatively correlated with the increase of urine K(+) and urine pH (P<0.01), while TMT did not change the expression of H(+)/K(+)-ATPase protein and mRNA. TMT decreased intracellular pH and opened K(+) channels in renal intercalated cells. Our findings suggest TMT can directly inhibit the activity of H(+)/K(+)-ATPases in renal intercalated cells, reducing urine K(+) reabsorption and inducing hypokalemia.

Occupational exposure to formaldehyde, hematotoxicity, and leukemia-specific chromosome changes in cultured myeloid progenitor cells.

There are concerns about the health effects of formaldehyde exposure, including carcinogenicity, in light of elevated indoor air levels in new homes and occupational exposures experienced by workers in health care, embalming, manufacturing, and other industries. Epidemiologic studies suggest that formaldehyde exposure is associated with an increased risk of leukemia. However, the biological plausibility of these findings has been questioned because limited information is available on the ability of formaldehyde to disrupt hematopoietic function. Our objective was to determine if formaldehyde exposure disrupts hematopoietic function and produces leukemia-related chromosome changes in exposed humans. We examined the ability of formaldehyde to disrupt hematopoiesis in a study of 94 workers in China (43 exposed to formaldehyde and 51 frequency-matched controls) by measuring complete blood counts and peripheral stem/progenitor cell colony formation. Further, myeloid progenitor cells, the target for leukemogenesis, were cultured from the workers to quantify the level of leukemia-specific chromosome changes, including monosomy 7 and trisomy 8, in metaphase spreads of these cells. Among exposed workers, peripheral blood cell counts were significantly lowered in a manner consistent with toxic effects on the bone marrow and leukemia-specific chromosome changes were significantly elevated in myeloid blood progenitor cells. These findings suggest that formaldehyde exposure can have an adverse effect on the hematopoietic system and that leukemia induction by formaldehyde is biologically plausible, which heightens concerns about its leukemogenic potential from occupational and environmental exposures.