Las misiones médicas al Policlínico PAMS en Chincha: evolución del modelo de misión / The medical missions to the PAMS Polyclinic in Chincha: evolution of the mission's model

RESUMEN Presentamos la experiencia del Policlínico de la Peruvian American Medical Society (PAMS) en Chincha, en la ejecución de misiones médico-educativas en la región Chincha. El Policlínico PAMS presta atención médica general y especializada a la población de la zona, seis días a la semana. Además, recibe misiones médicas que vienen generalmente de los EE. UU. Desde 2011, se han recibido 43 misiones médicas. La composición y la naturaleza de las misiones han cambiado con el tiempo. Los primeros años se atraía a especialistas con el énfasis de traer equipos e insumos para mejorar la infraestructura del Policlínico. Ahora estamos limitados por la renuencia de voluntarios de venir al Perú en parte debido a que el gobierno americano considera que viajes al Perú son de alto riesgo. Esta limitación nos ha brindado la oportunidad de hacer misiones médicas juntamente con dos excelentes universidades peruanas. La experiencia ha sido positiva.

ABSTRACT We present the experience of the Polyclinic of the Peruvian American Medical Society (PAMS) in Chincha, in the execution of medical educational missions in the Chincha region. The PAMS Polyclinic provides general and specialized medical care to the population of the area, six days a week. In addition, the Polyclinic receives medical missions generally coming from the EE.UU. Since 2011, we have received 43 medical missions. The composition and nature of the missions have changed over time. The first years attracted specialists with the emphasis on bringing equipment and supplies to improve the infrastructure of the Polyclinic. We are now limited by the reluctance of volunteers to come to Peru in part because the U.S. government considers travel to Peru to be high-risk. This limitation has given us the opportunity to do medical missions together with two excellent Peruvian universities. This experience has been positive.

El impacto de la pandemia del COVID-19 en la educación médica: adaptabilidad y experiencia con enseñanza a distancia de la Sociedad Médica Peruano Americana

La pandemia del COVID-19 tuvo un impacto significativo en el cuidado y la educación médicos en el Perú. En respuesta, la Sociedad Médica Peruano Americana (PAMS), una organización médica benéfica con sede en los EE.UU., adoptó sus misiones médicas y educativas en Perú usando estrategias virtuales. Desarrollamos colaboración con varias facultades de medicina y la Asociación Peruana de Facultades de Medicina (ASPEFAM) y ofrecimos un panel de veinte y cuatro miembros para brindar conferencias y seminarios multidisciplinarios en español. Hicimos 19 seminarios, incluyendo temas relacionados y no relacionados al COVID-19, que en los últimos dos años atrajo a 14 489 participantes de 23 países. Ellas fueron la base de 20 publicaciones en revistas médicas peruanas. Nuestro concurso de investigaciones clínicas y nuestro proyecto piloto de mentoría de investigación fueron recibidos positivamente. La pandemia del COVID-19 tuvo un efecto positivo en la misión educativa de PAMS en Perú.

The COVID-19 pandemic had a significant impact on medical care and medical education in Peru. In response, the Peruvian American Medical Society (PAMS), a charitable medical organization based in the USA, pursued its medical and educational missions in Peru by adopting virtual learning technology. We developed closer collaborative relationships with several medical schools and the Peruvian Association of Medical Schools (ASPEFAM) while offering a faculty panel of twenty-four members to provide lectures and multidisciplinary webinars in Spanish. We conducted 19 webinars including COVID -19 and non-COVID-19 related topics that over the last two years attracted 14,489 participants from 23 countries. They were the foundation for twenty publications in Peruvian medical journals. Our clinical investigations competition was positively received as was our pilot project on research mentorship. The COVID -19 pandemic had a positive effect on the educational mission of PAMS in Peru.

Dental caries in the peruvian police population.

BACKGROUND: Dental caries is a multifactorial disease that affects the general population. After reviewing the scientific literature, no studies were found on the index of decayed, missing and filled teeth (DMFT) in the Peruvian police population. The objective was to evaluate the DMFT index and severity level of the disease in police personnel of the Ancash region, Peru. MATERIAL AND METHODS: Cross-sectional prevalence study. The medical records of the police personnel in activity were reviewed and each subject was examined from May 2012 to May 2013. The study was authorized by the Director of the PNP-Huaraz Ancash Polyclinic as part of the activities of the civil SERUMS personnel in the area of odontology. The sample was census with 925 subjects. The data was systematized following the methodology recommended by the World Health Organization (WHO). The statistics were analyzed by Chi square test with significance p<0.05, Pearson test and ANOVA. RESULTS: The prevalence of caries in the police population was 73.4%. The DMFT index was 10.63 ± 4.96 (p<0.01). The severity of the disease in relation to age was 0.77 ± 0.41 with a high risk in this population. The DMFT index in females 128/925 and males 797/925 was 10.43 and 10.67 respectively. There is an inversely proportional relationship in the number of teeth filled with dental amalgam in policemen older than 35 years versus the number of teeth sealed with material other than dental amalgam in policemen under 35 years. Only 0.8% 7/925 had dental prostheses and 58.6% (542/925) of the subjects needed oral rehabilitation. CONCLUSIONS: The severity of dental caries is high, strategies are required to improve intervention in this sector, developing effective programs in oral health in the short, medium and long term. Key words:Dental caries severity, oral health, dental caries prevalence, peruvian police.

Low HIV/AIDS Knowledge among Hispanic Adolescents.

INTRODUCTION: Hispanic adolescents domiciling in Florida rank second in the U.S. with respect to HIV/AIDS incidence and prevalence. Extending studies showing that risky sexual behavior is associated with limited access to information, this project surveyed knowledge about HIV etiology, prevention and treatment. METHODS: The sample consisted of 400 Hispanic youth between 11-18 years of age living in Miami, Florida. The sample is enrolled in an ongoing project Role of Brain Derived Neurotrophic Factor in Decision Making (ROBIM). The HIV Knowledge Questionnaire (HIV-KQ-18), an 18 item self-administered questionnaire was used to measure HIV knowledge, particularly transmission and prevention. RESULTS: Less than 10% of the sample had comprehensive knowledge about HIV/AIDS. Approximately 25% incorrectly answered all of the questions. Questions pertaining to transmission were incorrectly answered by more than half of the sample. The most frequent topics reflecting absence of knowledge are related to high-risk sexual behaviors (sex during the menses) and infection prevention methods (e.g. condoms). A majority of youth believed incorrectly that HIV could be cured (61%), an effective vaccine is available (61%), and antibiotics protect against HIV infection (76%). School (28%) and parents (26%) were the most frequent sources of knowledge about HIV/AIDS. However, youth receiving information from parents had significantly higher knowledge scores than peers receiving education in school (7.4 ± 4.15 vs. 6.1 ± 4.5 scores, p = 0.037). Yet, 68% of the sample had never discussed condom use with their parents. CONCLUSIONS: These findings indicate Hispanic youths, although at very high risk, are poorly informed about prevention of HIV/AIDS. Moreover, the most frequent source of information, namely schools, inculcates less knowledge than parents. Lastly, youths who discuss sex with parents do not typically dialog about condoms, the most readily available protection from HIV/AIDS. These findings identify gaps that need to be addressed for lowering the high rate of HIV infection in Hispanic youths.

Inhibition of NANOG/NANOGP8 downregulates MCL-1 in colorectal cancer cells and enhances the therapeutic efficacy of BH3 mimetics.

PURPOSE: High levels of BCL-2 family members in colorectal carcinoma cause resistance to treatment. Inhibition of NANOG or its paralog NANOGP8 reduces the proliferation, stemness, and tumorigenicity of colorectal carcinoma cells. Our hypothesis was that inhibition of NANOG/NANOGP8 enhances the cytotoxic effect of BH3 mimetics targeting BCL-2 family members in colorectal carcinoma cells through reducing expression of MCL-1, a prosurvival BCL-2 protein. EXPERIMENTAL DESIGN: Lentiviral vector (LV) shRNA to NANOG (shNG-1) or NANOGP8 (shNp8-1) transduced colorectal carcinoma cells that were also exposed to the BH3 mimetics ABT-737 or ABT-199 in vivo in colorectal carcinoma xenografts and in vitro where proliferation, protein and gene expression, and apoptosis were measured. RESULTS: Clone A and CX-1 were sensitive to ABT-737 and ABT-199 at IC50s of 2 to 9 µmol/L but LS174T was resistant with IC50s of 18 to 30 µmol/L. Resistance was associated with high MCL-1 expression in LS174T. LVshNG-1 or LVshNp8-1 decreased MCL-1 expression, increased apoptosis, and decreased replating efficiency in colorectal carcinoma cells treated with either ABT-737 or ABT-199 compared with the effects of either BH3 mimetic alone. Inhibition or overexpression of MCL-1 alone replicated the effects of LVshNG-1 or LVshNp8-1 in increasing or decreasing the apoptosis caused with the BH3 mimetic. The combination therapy inhibited the growth of LS174T xenografts in vivo compared with untreated controls or treatment with only LV shRNA or ABT-737. CONCLUSIONS: Inhibition of NANOGP8 or NANOG enhances the cytotoxicity of BH3 mimetics that target BCL-2 family members. Gene therapy targeting the NANOGs may increase the efficacy of BH3 mimetics in colorectal carcinoma.

Dynamic analysis of global copper flows. Global stocks, postconsumer material flows, recycling indicators, and uncertainty evaluation.

We present a dynamic model of global copper stocks and flows which allows a detailed analysis of recycling efficiencies, copper stocks in use, and dissipated and landfilled copper. The model is based on historical mining and refined copper production data (1910-2010) enhanced by a unique data set of recent global semifinished goods production and copper end-use sectors provided by the copper industry. To enable the consistency of the simulated copper life cycle in terms of a closed mass balance, particularly the matching of recycled metal flows to reported historical annual production data, a method was developed to estimate the yearly global collection rates of end-of-life (postconsumer) scrap. Based on this method, we provide estimates of 8 different recycling indicators over time. The main indicator for the efficiency of global copper recycling from end-of-life (EoL) scrap--the EoL recycling rate--was estimated to be 45% on average, ± 5% (one standard deviation) due to uncertainty and variability over time in the period 2000-2010. As uncertainties of specific input data--mainly concerning assumptions on end-use lifetimes and their distribution--are high, a sensitivity analysis with regard to the effect of uncertainties in the input data on the calculated recycling indicators was performed. The sensitivity analysis included a stochastic (Monte Carlo) uncertainty evaluation with 10(5) simulation runs.

Effect of selected metal ions on the photocatalytic degradation of bog lake water natural organic matter.

Herein we report the photocatalytic degradation of natural organic matter from a bog lake (Lake Hohloh, Black Forest, Germany) in the presence of 0, 5, and 10 µmol L(-1) of added Cu(2+), Mn(2+), Zn(2+) and Fe(3+). The reactions were followed by size exclusion chromatography with organic carbon detection (SEC-DOC) and by measurements of low molecular weight organic acids. Addition of Cu(2+) had the largest effect of all four studied metals, leading to a retardation in the molecular size changes in NOM: degradation of the larger molecular weight fraction was inhibited leading to reduced production of smaller molecular weight metabolites. Similarly, addition of Cu(2+) reduced the production of formic and oxalic acids, and reduced the bioavailability of the partially degraded NOM.

Phenoxodiol inhibits growth of metastatic prostate cancer cells.

BACKGROUND: Phenoxodiol, a synthetic analog of Genistein, is being assessed in several clinical studies against a range of cancer types and was shown to have a good efficacy and safety profile. In this study we tested the effects of Phenoxodiol against prostate cancer cell lines. METHODS: Cell-cycle analysis, plasmatic membrane damage, clonogenic assay, comet assay, and Western blot methodologies were employed to assess the effects of Phenoxodiol on prostate cancer cell lines. An in vivo model confirmed the potential therapeutic efficacy of Phenoxodiol when administered orally to tumor bearing mice. RESULTS: Phenoxodiol treatment promoted a marked inhibition of proliferation and loss of colony formation in LNCaP cells in a dose- and time-dependent manner. Similar effects were also observed in the metastatic prostate cell lines PC3 and DU145. Activation of poly(ADP ribose) polymerase 1 (PARP-1) clearly indicates the induction of DNA damage by Phenoxodiol. Oral administration of Phenoxodiol induced a considerable growth inhibition of malignant tumors generated by inoculation of LNCaP cells into Balb/c nu/nu athymic mice. CONCLUSIONS: These data demonstrated that Phenoxodiol promotes apoptosis, as determined by PARP-1 degradation, via mitochondrial depolarization and G1/S cell-cycle arrest thereby confirming that it is active against androgen-dependent and independent prostate cancer cells. Although a precise target for Phenoxodiol has not been identified, these data contribute to our understanding of the mechanism by which this drug promotes cell death in prostate cancer cells, and warrants the continued clinical development of Phenoxodiol as a therapeutic for the treatment of metastatic prostate cancer.

Pharmacokinetic evaluation of rifabutin in combination with lopinavir-ritonavir in patients with HIV infection and active tuberculosis.

BACKGROUND: Human immunodeficiency virus (HIV)-associated tuberculosis is difficult to treat, given the propensity for drug interactions between the rifamycins and the antiretroviral drugs. We examined the pharmacokinetics of rifabutin before and after the addition of lopinavir-ritonavir. METHODS: We analyzed 10 patients with HIV infection and active tuberculosis in a state tuberculosis hospital. Plasma was collected for measurement of rifabutin, the microbiologically active 25-desacetyl-rifabutin, and lopinavir by validated high-performance liquid chromatography assays. Samples were collected 2-4 weeks after starting rifabutin at 300 mg thrice weekly without lopinavir-ritonavir, 2 weeks after the addition of lopinavir-ritonavir at 400 and 100 mg, respectively, twice daily to rifabutin at 150 mg thrice weekly, and (if rifabutin plasma concentrations were below the normal range) 2 weeks after an increase in rifabutin to 300 mg thrice weekly with lopinavir-ritonavir. Noncompartmental and population pharmacokinetic analyses (2-compartment open model) were performed. RESULTS: Rifabutin at 300 mg without lopinavir-ritonavir produced a low maximum plasma concentration (C(max)) in 5 of 10 patients. After the addition of lopinavir-ritonavir to rifabutin at 150 mg, 9 of 10 had low C(max) values. Eight patients had dose increases to 300 mg of rifabutin with lopinavir-ritonavir. Most free rifabutin (unbound to plasma protein) C(max) values were below the tuberculosis minimal inhibitory concentration. For most patients, values for the area under the plasma concentration-time curve were as low or lower than those associated with treatment failure or relapse and with acquired rifamycin resistance in Tuberculosis Trials Consortium/US Public Health Service Study 23. One of the 10 patients experienced relapse with acquired rifamycin resistance. CONCLUSION: The recommended rifabutin doses for use with lopinavir-ritonavir may be inadequate in many patients. Monitoring of plasma concentrations is recommended.

Formation of bromoform in irradiated titanium dioxide suspensions with varying photocatalyst, dissolved organic carbon and bromide concentrations.

We report the formation of bromoform in TiO(2) suspensions (P25) under simulated solar UV irradiation at different concentrations of photocatalyst (0.5-1.5 g L(-1)) as well as initial concentrations of bromide ions (1-3mg L(-1)) and 2,4-dihydroxybenzoic acid (2-10mg L(-1)). The extent of bromoform formation (3-17microg L(-1)) was most strongly affected by the amount of photocatalyst present and by the initial bromide concentration, increasing either of which leads to increased bromoform formation. Important interaction effects were observed when simultaneously increasing the concentrations of TiO(2) and bromide as well as of bromide and DHBA. The time it takes for bromoform to appear in measurable concentrations in the irradiated TiO(2) suspensions was between 10 and 90 min and most strongly depended on the initial concentration of dissolved organic carbon present in the suspensions, along with the amount of photocatalyst, also in interaction with the initial bromide concentration.

A simple simulation of the degradation of natural organic matter in homogeneous and heterogeneous advanced oxidation processes.

The degradation of natural organic matter (NOM) in homogeneous and heterogeneous advanced oxidation processes (AOP) was simulated using a simple underlying physical model. By treating the NOM molecules as linear chains and allowing them to be cleaved at any point selected at random, it is possible to reproduce well the results for homogeneous AOP experiments. To simulate a heterogeneous process, a bias was introduced (in the form of different weights for different chain lengths) according to literature data on the adsorption of NOM onto TiO(2) nanoparticle agglomerates. After introduction of the (adsorption) bias, the simulation closely followed the degradation sequence observed in heterogeneous photocatalysis with TiO(2) suspensions. Thus, the experimental results for homogeneous AOP may well be explained by a random breakdown of the NOM molecules; that is, we find no evidence for a selective degradation of the large molecular size material. However, a selectivity is present in the heterogeneous system due to the differential adsorption of NOM onto the reactive surface.

Formation of brominated products in irradiated titanium dioxide suspensions containing bromide and dissolved organic carbon.

We report the irradiation of TiO(2) suspensions containing Br(-) and dissolved organic carbon (DOC). In the absence of DOC, we found no evidence for the formation of BrO(3)(-) upon irradiation of 1gL(-1) P25 suspensions with UV light for initial Br(-) concentrations up to 10mgL(-1). In the presence of DOC (Lake Hohloh, Germany and salicylic acid), we found no evidence for the formation of either BrO(3)(-) or trihalomethanes (THMs). However, small amounts of adsorbable organic halogen (AOX) were formed at high bromide concentrations (3mgL(-1)). When irradiating P25 suspensions containing bromide and 2,4-dihydroxybenzoic acid (DHBA, high bromoform formation potential), we observed the formation of significant amounts of bromoform (up to 10microgL(-1)). Bromoform appeared only after the DHBA had been degraded.

An unusual cause of mastoiditis that evolved into multiple ring-enhancing intracerebral lesions in a person with HIV infection.

Acute mastoiditis, an infectious inflammatory process in the temporal bone, is an uncommon complication of otitis media. Here we describe a fatal case of mastoiditis complicated by thrombosis of the sigmoid sinus and intracerebral abscess caused by an unusual pathogen (Nocardia asteroides) in a person with HIV infection. Sulfonamides have remained the first-line agents for the management of Nocardia infections, but mortality remains high in patients with intracerebral infection.

The effect of nitrate, Fe(III) and bicarbonate on the degradation of bisphenol A by simulated solar UV-irradiation.

The photoinitiated degradation of bisphenol A (BPA, 520 micromol/L) was investigated using a solar simulator in the absence/presence of NO(3)(-), Fe(III), and HCO(3)(-). The concentrations of NO(3)(-), Fe(III), and HCO(3)(-) were 0-160, 0-10, and 0-820 micromol/L, respectively, and were chosen to simulate a natural aquatic environment. The experimental region was explored using a Box-Behnken design for three factors, extended to experimentally include all eight possible combinations of presence/absence of the factors studied. The results show that, after 7h of irradiation, photolysis occurs only to a minimal degree (2%) in the absence of NO(3)(-) and HCO(3)(-). Increasing the concentration of NO(3)(-) and HCO(3)(-) gives rise to up to 24% degradation after 7h of irradiation. The concentration of Fe(III) was found to play no active role under the conditions studied. A simple linear model is given that very well describes the results obtained.

Prolonged poly(ADP-ribose) polymerase-1 activity regulates JP-8-induced sustained cytokine expression in alveolar macrophages.

Environmental pollutants inducing oxidative stress stimulate chronic inflammatory responses in the lung leading to pulmonary tissue dysfunction. In response to oxidative stress, alveolar macrophages produce both reactive oxygen species and reactive nitrogen species, which induce the expression of a wide variety of immune-response genes. We found that a prolonged exposure of alveolar macrophages to a nonlethal dose (8 microg/ml) of JP-8, the kerosene-based hydrocarbon jet fuel, induced the persistent expression of IL-1, iNOS, and COX-2, as well as cell adhesion molecules (ICAM-1 and VCAM-1). Because poly(ADP-ribose) polymerase (PARP-1), a coactivator of NF-kappaB, regulates inflammatory responses and associated disorders in the airways, we determined whether JP-8 induces the poly(ADP-ribosyl)ation automodification of PARP-1 in alveolar macrophages. We observed that PARP-1 is activated in a time-dependent manner, which was temporally coincident with the prolonged activation of NF-kappaB and with the augmented expression of the proinflammatory factors described above. The 4 microg/ml dilution of JP-8 also increased the activity of PARP-1 as well as the expression of iNOS and COX-2, indicating that lower doses of JP-8 also affect the regulation of proinflammatory factors in pulmonary macrophages. Together, these results demonstrate that an extensive induction of PARP-1 might coordinate the persistent expression of proinflammatory mediators in alveolar macrophages activated by aromatic hydrocarbons that can result in lung injury from occupational exposure.

Using nonuniform electric fields to accelerate the transport of viruses to surfaces from media of physiological ionic strength.

Nonuniform ac (alternating current) electric fields created by microelectrodes are investigated for their influence on the transport of the vesicular stomatitis virus (VSV) from aqueous suspensions of physiological ionic strength to surfaces on which the VSV is captured. Whereas passive diffusion did not lead to detectable levels of virus captured on a surface when using titers of VSV as high as 107 PFU/mL, nonuniform electric field-mediated transport led to the detection of 105 PFU/mL of virus in 2 min. An order-of-magnitude analysis of the time scales associated with virus transport to the microelectrodes inside media of physiological relevance indicates that electrothermal fluid flow (and the resulting viscous drag forces on the virus) rather than dielectrophoresis likely constitutes the major mechanism for virus transport far from the electrodes. The influence of dielectrophoresis was calculated to be confined to a region within a few micrometers of the electrodes and to lead to collection patterns of both virus and fluorescently labeled particles near the electrodes that were found to be in qualitative agreement with experiments. These observations and conclusions are discussed within a theoretical framework presented in the paper. The results presented in this work, when combined, suggest that ac electrokinetic phenomena can be used to expeditiously transport and capture viruses onto surfaces from solutions of high ionic strength, thus providing a potentially useful approach to addressing a bottleneck in the development of devices that allow for rapid sampling and detection of infectious biological agents.

Protein kinase D 3 is localized in vesicular structures and interacts with vesicle-associated membrane protein 2.

Protein kinase D localizes in the Golgi and regulates protein transport from the Golgi to the plasma membrane. In the present study, we found that PKD3, a novel member of the PKD family, and its fluorescent protein fusions localized in the Golgi and in the vesicular structures that are in part marked by endosome markers. Fluorescent recovery after photobleaching (FRAP) showed that the PKD3-associated vesicular structures were constantly forming and dissolving, reflecting active subcellular structures. FRAP on plasma membrane-located PKD3 indicated a slower recovery of PKD3 fluorescent signal compared to those of PKC isoforms, implying a different targeting mechanism at the plasma membrane. VAMP2, the vesicle-localized v-SNARE, was later identified as a novel binding partner of PKD3 through yeast two-hybrid screening. PKD3 directly interacted with VAMP2 in vitro and in vivo, and colocalized in part with VAMP2 vesicles in cells. PKD3 did not phosphorylate VAMP-GFP and the purified GST-VAMP2 protein in in vitro phosphorylation assays. Rather, PKD3 was found to promote the recruitment of VAMP2 vesicles to the plasma membrane in response to PMA, while the kinase dead PKD3 abolished this effect. Thus, the kinase activity of PKD3 was required for PMA-induced plasma membrane trafficking of VAMP2. In summary, our findings suggest that PKD3 localizes to vesicular structures that are part of the endocytic compartment. The vesicular distribution may be attributed in part to the direct interaction between PKD3 and vesicle-associated membrane protein VAMP2, through which PKD3 may regulate VAMP2 vesicle trafficking by facilitating its recruitment to the target membrane.

Expression of JP-8-induced inflammatory genes in AEII cells is mediated by NF-kappaB and PARP-1.

Lung epithelial cells are critical in the regulation of airway inflammation in response to environmental pollutants. Altered activation of NF-kappaB is associated with expression of several proinflammatory factors in respiratory epithelial cells in response to an insult. Here we show that a low threshold dose (8 microg/ml) of the jet fuel JP-8 induces in a rat alveolar epithelial cell line (RLE-6TN) a prolonged activation of NF-kappaB as well as the increased expression of the proinflammatory cytokines TNF-alpha and IL-8, which are regulated by NF-kappaB. The up-regulation of IL-6 mRNA in cells exposed to JP-8 appears to be a reaction of RLE-6TN cells to reduce the enhancement of proinflammatory mediators in response to the fuel. Moreover, lung tissues from rats exposed to occupational levels of JP-8 by nasal aerosol also showed dysregulated expression of TNF-alpha, IL-8, and IL-6, confirming the in vitro data. The poly(ADP-ribosyl)ation of PARP-1, a coactivator of NF-kappaB, was coincident with the prolonged activation of NF-kappaB during JP-8 treatment. These results evidenced that a persistent exposure of the airway epithelium to aromatic hydrocarbons may have deleterious effects on pulmonary function.

Altered expression of gamma-synuclein and detoxification-related genes in lungs of rats exposed to JP-8.

Many military personnel are at risk of lung damage or systemic toxicity as a result of exposure to the jet fuel JP-8. We have now used microarray analysis to characterize changes in the gene expression profile of lung tissue induced by exposure of rats to JP-8 at a concentration of 171 or 352 mg/m(3) for 1 h/d for 7 d, with the higher dose estimated to mimic the level of occupational exposure in humans. The expression of 56 genes was significantly affected by a factor of /= 1.5 by JP-8 at the low dose. Eighty-six percent of these genes were downregulated by JP-8. The expression of 66 genes was similarly affected by JP-8 at the higher dose, with the expression of 42% of these genes being upregulated. Prominent among the latter genes was that for the centrosome-associated protein gamma-synuclein, whose expression was consistently increased. The expression of various genes related to antioxidant responses and detoxification, including those for glutathione S-transferases and cytochrome P450 proteins, were also upregulated. The microarray data were confirmed by quantitative RT-PCR analysis. Our extensive data set may thus provide important insight into the pulmonary response to occupational exposure to JP-8 in humans.

Evaluation of gene expression profile of keratinocytes in response to JP-8 jet fuel.

The skin is the principal barrier against any environmental insult. Therefore, there is a high risk for a large number of military and civilian personnel exposed to jet fuel JP-8 to suffer percutaneous absorption of this fuel. This paper reports the use of cDNA microarray to identify the gene expression profile in normal human epidermal keratinocytes exposed to JP-8 for 24-h and 7-day periods. The effects of JP-8 exposure on keratinocytes at these two different periods induced a set of genes with altered expression in response to this type of insult. Microarray data were visualized using a novel algorithm based on simple statistical analyses to reduce data dimensionality and identify subsets of discriminant genes. Predictive neural networks were built using a multiplayer perceptron to carry out a proper classification task in microarray data in the untreated versus JP-8-treated samples. The pattern of expressions in response to JP-8 provides evidences that detoxificant-related and cell growth regulator genes with the most variability in the level of expression may be useful genetic markers in adverse health effects of personnel exposed to JP-8. The approaches in our analysis provide a simple, safe, novel, and effective method that is reliable in identifying and analyzing gene expression in samples treated with JP-8 or over potential toxic agents. Gene expression data from these studies can be used to build accurate predictive models that separate different molecular profiles. The data establish the use and effectiveness of these approaches for future prospective studies.