Spatial distribution of orofacial cleft birth defects and uranium-radium concentrations in tap water in Atascosa, Bee, Brooks, Calhoun, Duval, Goliad, Hidalgo, Jim Hogg, Jim Wells, Karnes, Kleberg, Live Oak, McMullen, Nueces, San Patricio, Refugio, Starr, Victoria, Webb, and Zavala Counties, Texas

Background Past and recent evidence shows that radionuclides in drinking water may be a public health concern. Developmental thresholds for birth defects with respect to chronic low level domestic radiation exposures, such as through drinking water, have not been definitely recognized, and there is a strong need to address this deficiency in information. In this study we examined the geographic distribution of orofacial cleft birth defects in and around uranium mining district Counties in South Texas (Atascosa, Bee, Brooks, Calhoun, Duval, Goliad, Hidalgo, Jim Hogg, Jim Wells, Karnes, Kleberg, Live Oak, McMullen, Nueces, San Patricio, Refugio, Starr, Victoria, Webb, and Zavala), from 1999 to 2007. The probable association of cleft birth defect rates by ZIP codes classified according to uranium and radium concentrations in drinking water supplies was evaluated. Similar associations between orofacial cleft birth defects and radium/radon in drinking water were reported earlier by Cech and co-investigators in another of the Gulf Coast region (Harris County, Texas).50, 55 Since substantial uranium mining activity existed and still exists in South Texas, contamination of drinking water sources with radiation and its relation to birth defects is a ground for concern. ^ Methods Residential addresses of orofacial cleft birth defect cases, as well as live births within the twenty Counties during 1999-2007 were geocoded and mapped. Prevalence rates were calculated by ZIP codes and were mapped accordingly. Locations of drinking water supplies were also geocoded and mapped. ZIP codes were stratified as having high combined uranium (≥30μg/L) vs. low combined uranium (<30μg/L). Likewise, ZIP codes having the uranium isotope, Ra-226 in drinking water, were also stratified as having elevated radium (≥3 pCi/L) vs. low radium (<3 pCi/L). A linear regression was performed using STATA® generalized linear model (GLM) program to evaluate the probable association between cleft birth defect rates by ZIP codes and concentration of uranium and radium via domestic water supply. These rates were further adjusted for potentially confounding variables such as maternal age, education, occupation, and ethnicity. ^ Results This study showed higher rates of cleft births in ZIP codes classified as having high combined uranium versus ZIP codes having low combined uranium. The model was further improved by adding radium stratified as explained above. Adjustment for maternal age and ethnicity did not substantially affect the statistical significance of uranium or radium concentrations in household water supplies. ^ Conclusion Although this study lacks individual exposure levels, the findings suggest a significant association between elevated uranium and radium concentrations in tap water and high orofacial birth defect rates by ZIP codes. Future case-control studies that can measure individual exposure levels and adjust for contending risk factors could result in a better understanding of the exposure-disease association.^

Drinking water quality perception along the U.S.-Mexico border

Drinking water-related exposures within populations living in the United States-Mexico border region, particularly among Hispanics, is an area that is largely unknown. Specifically, perceptions that may affect water source selection is an issue that has not been fully addressed. This study evaluates drinking water quality perceptions in a mostly Hispanic community living along the United States-Mexico border, a community also facing water scarcity issues. Using a survey that was administered during two seasons (winter and summer), data were collected from a total of 608 participants, of which 303 were living in the United States and 305 in Mexico. A (random) convenience sampling technique was used to select households and those interviewed were over 18 years of age. Statistically significant differences were observed involving country of residence (p=0.002). Specifically, those living in Mexico reported a higher use of bottled water than those living in the United States. Perception factors, especially taste, were cited as main reasons for not selecting unfiltered tap water as a primary drinking water source. Understanding what influences drinking water source preference can aid in the development of risk communication strategies regarding water quality. ^

A standard operation procedure and a pilot water testing for herbicides in northwest Harris County, Texas

Herbicides are used to control the growth of weeds along highways, power lines, and many other urban locations. Exposure to herbicides has been linked to adverse health outcomes. This study was initiated to pretest for the presence of herbicides in multiple water sources near intersections in a corridor in the Northwest Harris County (specifically in the Highway 6/FM 1960, North Freeway 45, US 290 and S 99 corridor). Roadside water and tap water samples were collected and analyzed for herbicides using the established Environmental Protection Agency (EPA) Method 515.4: "Determination of Chlorinated Acids in Drinking Water by Liquid-Liquid Micro-extraction, Derivatization, and Fast Gas Chromatography with Electron Capture Detection." A standard operating procedure (adapted from the US EPA Method 515.4) was developed for subsequent, larger studies of environmental fate of herbicides and non-occupational exposure risks. Preliminary testing of 16 water samples was performed to pretest the existence of trace herbicides; all concentrations that were greater than the minimum reporting limits of each analyte are reported with a 99 percent confidence. This study failed to find concentrations above the limits of detection of the method in any of the samples collected on June 15, 2008. However, this does not indicate that the waters around the NW Harris County are free of herbicides and metabolites. A larger and repeated sampling in the region would be necessary to make that claim. ^

IMMUNE MODULATION OF THE MYCOBACTERIUM TUBERCULOSIS GRANULOMATOUS RESPONSE

Tuberculosis (TB) remains a major public health burden. The immunocompetant host responds to Mycobacterium tuberculosis (MTB) infection by the formation of granulomas, which initially prevent uncontrolled bacterial proliferation and dissemination. However, increasing evidence suggests that granuloma formation promotes persistence of the organism by physically separating infected cells from effector lymphocytes and by inducing a state of non-replicating persistence in the bacilli, making them resistant to the action of antibiotics. Additionally, immune-mediated tissue destruction likely facilitates disease transmission. The granulomatous response is in part due to mycobacterial glycolipid antigens. Therefore, studies were first undertaken to determine the innate mechanisms of mycobacterial cord factor trehalose-6’6-dimycolate (TDM) on granuloma formation. Investigations using knock-out mice suggest that TNF-a is involved in the initiation of the granulomatous response, complement factor C5a generates granuloma cohesiveness, and IL-6 is necessary for maintenance of an established granulomatous responses. Studies were next performed to determine the ability of lactoferrin to modulate the immune response and pathology to mycobacterial cord factor. Lactoferrin is an iron-binding glycoprotein with immunomodulatory properties that decrease tissue damage and promote Th1 responses. Mice challenged with TDM and treated with lactoferrin had decreased size and numbers of granulomas at the peak of the granulomatous response, accompanied by increased IL-10 and TGF-b production. Finally, the ability of lactoferrin to serve as a novel therapeutic for the treatment of TB was performed by aerosol challenging mice with MTB and treating them with lactoferrin added to the drinking water. Mice given tap water had lung log10 CFUs of 7.5 ± 0.3 at week 3 post-infection. Lung CFUs were significantly decreased in mice given lactoferrin starting the day of infection (6.4 ± 0.7) and mice started therapeutically on lactoferrin at day 7 after established infection (6.5 ± 0.4). Total lung inflammation in lactoferrin treated mice was significantly decreased, with fewer areas of macrophages, increased total lymphocytes, and increased numbers of CD4+ and CD8+ cells. The lungs of lactoferrin treated mice had increased CD4+ IFN-g+ cells and IL-17 producing cells on ELISpot analysis. It is hypothesized that lactoferrin decreases bacterial burden during MTB infection by early induction of Th1 responses.

APPLICATION OF THE BRAINSTEM EVOKED RESPONSE (BER) TO NEUROTOXICITY EVALUATION OF THE AUDITORY SYSTEM: ASSESSMENT OF INORGANIC LEAD-INDUCED OTOTOXICITY

An experimental procedure was developed using the Brainstem Evoked Response (BER) electrophysiological technique to assess the effect of neurotoxic substances on the auditory system. The procedure utilizes Sprague-Dawley albino rats who have had dural electrodes implanted in their skulls, allowing neuroelectric evoked potentials to be recorded from their brainstems. Latency and amplitude parameters derived from the evoked potentials help assess the neuroanatomical integrity of the auditory pathway in the brainstem. Moreover, since frequency-specific auditory stimuli are used to evoke the neural responses, additional audiometric information is obtainable. An investigation on non-exposed control animals shows the BER threshold curve obtained by tests at various frequencies very closely approximates that obtained by behavioral audibility tests. Thus, the BER appears to be a valid measure of both functional and neuroanatomical integrity of the afferent auditory neural pathway.^ To determine the usefulness of the BER technique in neurobehavioral toxicology research, a known neurotoxic agent, Pb, was studied. Female Sprague-Dawley rats were dosed for 45 days with low levels of Pb acetate in their drinking water, after which BER recordings were obtained. The Pb dosages were determined from the findings of an earlier pilot study. One group of 6 rats received normal tap water, one group of 7 rats received a solution of 0.1% Pb, and another group of 7 rats received a solution of 0.2% Pb. After 45 days, the three groups exhibited blood Pb levels of 4.5 (+OR-) 0.43 (mu)g/100 ml, 37.8 (+OR-) 4.8 (mu)g/100 ml and 47.3 (+OR-) 2.7 (mu)g/100 ml, respectively.^ The results of the BER recording indicated evoked response waveform latency abnormalities in both the Pb-treated groups when midrange frequency (8 kHz to 32 kHz) stimuli were used. For the most part, waveform amplitudes did not vary significantly from control values. BER recordings obtained after a 30-day recovery period indicated the effects seen in the 0.1% Pb group had disappeared. However, those anomalies exhibited by the 0.2% Pb group either remained or increased in number. This outcome indicates a longer lasting or possibly irreversible effect on the auditory system from the higher dose of Pb. The auditory pathway effect appears to be in the periphery, at the level of the cochlea or the auditory (VIII) nerve. The results of this research indicate the BER technique is a valuable and sensitive indicator of low-level toxic effects on the auditory system.^