Nicotine e-cigarette vapor inhalation effects on nicotine & cotinine plasma levels and somatic withdrawal signs in adult male Wistar rats.

RATIONALE: Non-contingent chronic nicotine exposure procedures have evolved rapidly in recent years, culminating in electronic nicotine delivery systems (ENDS or e-cigarettes) to deliver vaporized drugs to rodents in standard housing chambers. OBJECTIVES: The aim of the current work was to use ENDS to test concentration-dependent effects of nicotine e-cigarette vapor inhalation on blood-nicotine concentrations, blood-cotinine concentrations, and somatic withdrawal signs over time in rats. METHODS: Male Wistar rats were exposed to vapor containing various concentrations of nicotine (20, 40, 80 mg/mL) for 11 days through ENDS, and blood concentrations of nicotine and cotinine, the major proximate metabolite of nicotine, as well as spontaneous and precipitated somatic withdrawal signs, were measured over time (across days of exposure and over hours after termination of vapor exposure). RESULTS: Exposing male Wistar rats to non-contingent nicotine vapor inhalation through ENDS produces somatic withdrawal symptoms and measurable blood-nicotine and blood-cotinine levels that change according to (1) concentration of nicotine in vape solution, (2) number of days of nicotine vapor exposure, (3) time since termination of nicotine vapor exposure, and (4) relative to the withdrawal signs, whether withdrawal was spontaneous or precipitated (by mecamylamine). CONCLUSIONS: The data presented here provide parameters that can be used as a reasonable starting point for future work that employs ENDS to deliver non-contingent nicotine vapor in rats, although many parameters can and should be altered to match the specific goals of future work.

Lowering barometric pressure induces neuronal activation in the superior vestibular nucleus in mice.

Weather changes accompanied by decreases in barometric pressure are suggested to trigger meteoropathy, i.e., weather-related pain. We previously reported that neuropathic pain-related behavior in rats is aggravated by lowering barometric pressure, and that this effect is abolished by inner ear lesions. These results suggest that mechanisms that increase vestibular neuronal activity may parallel those that contribute to meteoropathy generation. However, it remains unknown whether changes in barometric pressure activate vestibular neuronal activity. To address this issue, we used expression of c-Fos protein as a marker for neural activation. Male and female mice were placed in a climatic chamber, and the barometric pressure was lowered by 40 hPa, from 1013 hPa, for 50 min (LP stimulation). The total number of c-Fos-positive cells in the vestibular nuclei was counted bilaterally after LP stimulation. We also video-recorded mouse behaviors and calculated the total activity score during the LP stimulation. LP stimulation resulted in significant c-Fos expression in the superior vestibular nucleus (SuVe) of male and female mice. There was no effect of LP stimulation on the total activity score. These data show that distinct neurons in the SuVe respond to LP stimulation. Similar mechanisms may contribute to the generation of meteoropathy in humans.

Análisis de los efectos de la hipoxia en 236 pilotos durante el entrenamiento fisiológico en cámara hipobárica / Analysis of the effects of hypoxy in 236 pilots during physiological training in hyperbaric chamber

Introducción: La hipoxia se define como un estado de deficiencia de oxígeno en el organismo. La reducción de la presión parcial de oxigeno como consecuencia de la reducción de la presión atmosférica con la altitud, establece la hipoxia hipobárica, cuyos síntomas pueden ser estudiados durante el entrenamiento fisiológico de altura. Dicha prueba es una herramienta fundamental, para entrenar a los pilotos mediante equipos en tierra que simulan fielmente las condiciones de un vuelo real, con el propósito de que aprendan a reconocer los síntomas y entrenen la forma de manejarlos cuando estén en vuelo. Ejemplo de este tipo de entrenamiento es el realizado en la cámara de altitud o hipobárica. Objetivos: Analizar los efectos de la hipoxia hipobárica en 236 pilotos de avión. Material y Método: Se tomaron los datos estadísticos de los archivos del departamento de investigación del INMAE de pilotos militares sometidos a la prueba de hipoxia en la cámara hipobárica. Se realizó un estudio retrospectivo, descriptivo, el criterio de inclusión fue de pilotos militares activos sometidos a prueba de hipoxia en cámara hipobárica a una altura de 27.500 que presentaron al menos un síntoma durante la prueba, la muestra final incluyó a 236 casos. Resultados: Se analizaron los datos de 236 pilotos de avión, todos ellos fueron hombres, las edades oscilaron entre 20 y 55 años, la edad media fue de 32 (31,76) años +/-6.8. Los síntomas más frecuentes fueron: calor en general (41.5%), describieron calor en todo el cuerpo y en zonas específicas de las cuales la más frecuente fue la cara (55% del total de calor)le siguieron las manos y las plantas de los pies, parestesias (11.8%), vértigo (9.7%), definida como la dificultad respiratoria con sensación de falta de aires la disnea se presentó en cuarto lugar (8.9%) y también se describieron alteraciones de la visión (7.2%) tales como visión nublada, visión en túnel y visión negra. En cuanto al TUC osciló entre 43 y 226 segundos, el promedio fue de 119 segundos. Conclusiones: Los síntomas más frecuentes fueron Calor sobre todo en la cara, manos y pies, parestesias, vértigo, disnea, alteraciones de la visión, palpitaciones, sudoración, temblor, cianosis, dolor de cabeza, alteraciones cognitivas. El TUC osciló entre 43 y 226 segundos, el promedio fue de 119 segundos. Al comparar el TUC con los grupos de edades establecidos (mayores y menores de 40 años), existe diferencia entre el promedio de los menores de 40 años (121 segundos) y mayores de esa edad (110 segundos) que habla a favor de una relación inversa entre ambas variables, es decir, a mayor edad menor TUC, estadísticamente obtuvimos, con una probabilidad entre 98 y 99 %, que después de los 40 años el tuc disminuye aproximadamente 10%.

Introduction: Hypoxia is defined as a state of oxygen deficiency in the body. The reduction of the oxygen partial pressure as a consequence of the reduction of the atmospheric pressure with the altitude, establishes the hypobaric hypoxia, whose symptoms can be studied during the physiological training of height. This test is a fundamental tool to train pilots using ground equipment that faithfully simulate the conditions of a real flight, so that they learn to recognize the symptoms and train how to handle them when they are in flight. An example of this type of training is that performed in the altitude or hypobaric chamber. Objectives: To analyze the effects of hypobaric hypoxia on 236 aircraft pilots. Material and method: Statistical data were taken from the files of the INMAE research department of military pilots subjected to hypoxia testing in the hypobaric chamber. A retrospective, descriptive study was performed. The inclusion criterion was that of active military pilots who underwent a hypoxia test in a hypobaric chamber at a height of 27,500 who presented at least one symptom during the test. The final sample included 236 cases. Results: We analyzed the data of 236 airplane pilots, all of them men, the ages ranged from 20 to 55 years, the average age was 32 years. The most frequent symptoms were: heat in general, described heat throughout the body and in specific areas of which the most frequent was the face followed by the hands and soles of the feet, paresthesias, vertigo, defined as respiratory difficulty with Sensation of shortness of breath, dyspnea presented in fourth place and also described alterations of vision such as cloudy vision, tunnel vision and black visión Useful time of consciousness (UTC) ranged from 43 to 226 seconds, averaging 119 seconds. Conclusions: The most frequent symptoms were: heat, the most frequent was the face followed by the hands and soles of the feet, paresthesias, vertigo, dyspnea, sweat, palpitations, tremors, cyanosis, headache, cognitive alterations. Useful time of consciousness (UTC) ranged from 43 to 226 seconds, averaging 119 seconds. When comparing UTC with established age groups (older and younger than 40 years), we obtained, with a probability of 98-99%, that after 40 years UTC decreased by approximately 10%.

Exacerbation of atopic dermatitis on grass pollen exposure in an environmental challenge chamber.

BACKGROUND: It has frequently been speculated that pruritus and skin lesions develop after topical exposure to aeroallergens in sensitized patients with atopic dermatitis (AD). OBJECTIVE: We sought to study cutaneous reactions to grass pollen in adult patients with AD with accompanying clear IgE sensitization to grass allergen in an environmental challenge chamber using a monocenter, double-blind, placebo-controlled study design. METHODS: Subjects were challenged on 2 consecutive days with either 4000 pollen grains/m(3) of Dactylis glomerata pollen or clean air. The severity of AD was assessed at each study visit up to 5 days after challenge by (objective) scoring of AD (SCORAD). Additionally, air-exposed and non-air-exposed skin areas were each scored using local SCORAD scoring and investigator global assessments. Levels of a series of serum cytokines and chemokines were determined by using a Luminex-based immunoassay. The primary end point of the study was the change in objective SCORAD scores between prechallenge and postchallenge values. RESULTS: Exposure to grass pollen induced a significant worsening of AD. A pronounced eczema flare-up of air-exposed rather than covered skin areas occurred. In grass pollen-exposed subjects a significantly higher increase in CCL17, CCL22, and IL-4 serum levels was observed. CONCLUSIONS: This study demonstrates that controlled exposure to airborne allergens of patients with a so-called extrinsic IgE-mediated form of AD induced a worsening of cutaneous symptoms.

Decompression sickness following altitude-chamber training.

Decompression sickness (DCS) is one of several dysbarisms (medical conditions resulting from a change in atmospheric pressure) that can be encountered by the Special Operations Forces (SOF) medical provider. DCS can present with several different manifestations. The authors present the case of a 23-year-old Airman who presented with vague neurologic symptoms following altitude-chamber training. They discuss the care of casualties with DCS and its implications for SOF.

Ontogeny and adolescent alcohol exposure in Wistar rats: open field conflict, light/dark box and forced swim test.

Epidemiological studies have demonstrated that heavy drinking and alcohol abuse and dependence peak during the transition between late adolescence and early adulthood. Studies in animal models have demonstrated that alcohol exposure during adolescence can cause a modification in some aspects of behavioral development, causing the "adolescent phenotype" to be retained into adulthood. However, the "adolescent phenotype" has not been studied for a number of behavioral tests. The objective of the present study was to investigate the ontogeny of behaviors over adolescence/young adulthood in the light/dark box, open field conflict and forced swim test in male Wistar rats. These data were compared to previously published data from rats that received intermittent alcohol vapor exposure during adolescence (AIE) to test whether they retained the "adolescent phenotype" in these behavioral tests. Three age groups of rats were tested (post-natal day (PD) 34-42; PD55-63; PD69-77). In the light/dark box test, younger rats escaped the light box faster than older adults, whereas AIE rats returned to the light box faster and exhibited more rears in the light than controls. In the open field conflict test, both younger and AIE rats had shorter times to first enter the center, spent more time in the center of the field, were closer to the food, and consumed more food than controls. In the forced swim test no clear developmental pattern emerged. The results of the light/dark box and the forced swim test do not support the hypothesis that adolescent ethanol vapor exposure can "lock-in" all adolescent phenotypes. However, data from the open field conflict test suggest that the adolescent and the AIE rats both engaged in more "disinhibited" and food motivated behaviors. These data suggest that, in some behavioral tests, AIE may result in a similar form of behavioral disinhibition to what is seen in adolescence.

Central retinal vein occlusion following hypobaric chamber exposure.

BACKGROUND: Mountain climbers who ascend to a high altitude could suffer high altitude retinopathy, which varies from tortuous retinal vessels and hemorrhages to retinal vascular obstruction. As hypobaric chamber training could imitate a fast ascent and could lead to decompression sickness, a simulated flight could also lead to a high altitude retinopathy. CASE REPORT: This paper will present a case of central retinal vein occlusion that occurred after exposure to a hypobaric chamber and Valsalva maneuver. Although the patient was treated with an intravitreal bevacizumab injection, his macular edema was aggravated after a helicopter flight, which involved re-exposure to high altitudes and a Valsalva maneuver. DISCUSSION: Systemic evaluation including blood coagulation and carotid Doppler studies did not reveal any lesion. Notably, central retinal vein occlusion can occur in young, healthy individuals after hypobaric chamber exposure.

Ozone exposure during the early postnatal period alters the timing and pattern of alveolar growth and development in nonhuman primates.

Exposure to oxidant air pollutants in early childhood, with ozone as the key oxidant, has been linked to significant decrements in pulmonary function in young adults and exacerbation of airway remodeling in asthma. Development of lung parenchyma in rhesus monkeys is rapid during the first 2 years of life (comparable to the first 6 years in humans). Our hypothesis is that ozone inhalation during infancy alters alveolar morphogenesis. We exposed infant rhesus monkeys biweekly to 5, 8 hr/day, cycles of 0.5 ppm ozone with or without house dust mite allergen from 1 to 3 or 1 to 6 months of age. Monkeys were necropsied at 3 and 6 months of age. A morphometric approach was used to quantify changes in alveolar volume and number, the distribution of alveolar size, and capillary surface density per alveolar septa. Quantitative real time PCR was used to measure the relative difference in gene expression over time. Monkeys exposed to ozone alone or ozone combined with allergen had statistically larger alveoli that were less in number at 3 months of age. Alveolar capillary surface density was also decreased in the ozone exposed groups at 3 months of age. At 6 months of age, the alveolar number was similar between treatment groups and was associated with a significant rise in alveolar number from 3 to 6 months of age in the ozone exposed groups. This increase in alveolar number was not associated with any significant increase in microvascular growth as measured by morphometry or changes in angiogenic gene expression. Inhalation of ozone during infancy alters the appearance and timing of alveolar growth and maturation. Understanding the mechanism involved with this altered alveolar growth may provide insight into the parenchymal injury and repair process that is involved with chronic lung diseases such as severe asthma and COPD.

Enriched environment prevents hypobaric hypoxia induced neurodegeneration and is independent of antioxidant signaling.

Hypobaric hypoxia (HH) induced neurodegeneration has been attributed to several factors including increased oxidative stress, glutamate excitotoxicity, decreased growth factors, apoptosis, etc. Though enriched environment (EE) has been known to have beneficial effects in various neurological disorders, its effect on HH mediated neurodegeneration remains to be studied. Therefore, the present study was conducted to explore the effect of EE on HH induced neurodegeneration. Male Sprague-Dawley rats were placed in enriched and standard conditions during exposure to HH (7 days) equivalent to an altitude of 25,000 ft. The effect of EE on oxidative stress markers, apoptosis, and corticosterone level in hippocampus was investigated. EE during exposure to HH was found to decrease neurodegeneration as evident from decreased caspase 3 expression and LDH leakage. However, no significant changes were observed in ROS, MDA, and antioxidant status of hippocampus. HH elevates corticosterone level and affected the diurnal corticoid rhythm which may contribute to neurodegeneration, whereas EE ameliorate this effect. Because of the association of neurotrophins and stress and/or corticosterone the BDNF and NGF levels were also examined and it was found that HH decreases their level but concurrent exposure to EE maintains their level. Moreover, inhibition of Tyrosine kinase receptor (Trk) with K252a nullifies the protective effect of EE, whereas Trk activation with agonist, amitriptyline showed protective effect similar to EE. Taken together, we conclude that EE has a potential to ameliorate HH mediated neuronal degeneration which may act through antioxidant independent pathway by modulation of neurotrophins.

Effect of controlled adverse chamber environment exposure on tear functions in silicon hydrogel and hydrogel soft contact lens wearers.

PURPOSE: To prospectively evaluate the effect of controlled adverse chamber environment (CACE) exposure on tear function, including tear osmolarity, in subjects wearing narafilcon A versus those wearing etafilcon A soft contact lens (SCL). METHODS: Thirty-one healthy subjects with no history of contact lens wear (13 women, 18 men; average age, 30.5 ± 6.5 years) were randomly divided into age- and sex-matched groups (15 subjects wearing narafilcon A SCL; 16 subjects wearing etafilcon A SCL) and entered a CACE for 20 minutes. All subjects underwent tear osmolarity, tear evaporation rate, strip meniscometry, tear film breakup time, fluorescein vital staining, and functional visual acuity measurement before and after exposure to the controlled adverse chamber. RESULTS: The mean blink rate increased with significant deteriorations in the mean symptom VAS scores, mean tear osmolarity, tear evaporation rate, strip meniscometry score, and tear stability with CACE exposure along with a decrease in visual maintenance ratio in functional visual acuity testing in etafilcon A wearers. The mean symptom VAS scores, mean tear evaporation rate, tear stability, blink rates, and visual maintenance ratios did not change significantly in narafilcon A wearers after CACE exposure. CONCLUSIONS: This study suggested marked tear instability, higher tear osmolarity, and increased tear evaporation with marked dry eye and visual symptomatology in nonadapted hydrogel SCL wearers, suggesting that silicone hydrogel SCLs may be suitable for persons who live and work in cool, low-humidity, and windy environments, as tested in this study.

The pathobiology of blast injuries and blast-induced neurotrauma as identified using a new experimental model of injury in mice.

Current experimental models of blast injuries used to study blast-induced neurotrauma (BINT) vary widely, which makes the comparison of the experimental results extremely challenging. Most of the blast injury models replicate the ideal Friedländer type of blast wave, without the capability to generate blast signatures with multiple shock fronts and refraction waves as seen in real-life conditions; this significantly reduces their clinical and military relevance. Here, we describe the pathophysiological consequences of graded blast injuries and BINT generated by a newly developed, highly controlled, and reproducible model using a modular, multi-chamber shock tube capable of tailoring pressure wave signatures and reproducing complex shock wave signatures seen in theater. While functional deficits due to blast exposure represent the principal health problem for today's warfighters, the majority of available blast models induces tissue destruction rather than mimic functional deficits. Thus, the main goal of our model is to reliably reproduce long-term neurological impairments caused by blast. Physiological parameters, functional (motor, cognitive, and behavioral) outcomes, and underlying molecular mechanisms involved in inflammation measured in the brain over the 30 day post-blast period showed this model is capable of reproducing major neurological changes of clinical BINT.

Evaluation of precision and accuracy of the Borgwaldt RM20S(®) smoking machine designed for in vitro exposure.

The Borgwaldt RM20S(®) smoking machine enables the generation, dilution, and transfer of fresh cigarette smoke to cell exposure chambers, for in vitro analyses. We present a study confirming the precision (repeatability r, reproducibility R) and accuracy of smoke dose generated by the Borgwaldt RM20S(®) system and delivery to exposure chambers. Due to the aerosol nature of cigarette smoke, the repeatability of the dilution of the vapor phase in air was assessed by quantifying two reference standard gases: methane (CH(4), r between 29.0 and 37.0 and RSD between 2.2% and 4.5%) and carbon monoxide (CO, r between 166.8 and 235.8 and RSD between 0.7% and 3.7%). The accuracy of dilution (percent error) for CH(4) and CO was between 6.4% and 19.5% and between 5.8% and 6.4%, respectively, over a 10-1000-fold dilution range. To corroborate our findings, a small inter-laboratory study was carried out for CH(4) measurements. The combined dilution repeatability had an r between 21.3 and 46.4, R between 52.9 and 88.4, RSD between 6.3% and 17.3%, and error between 4.3% and 13.1%. Based on the particulate component of cigarette smoke (3R4F), the repeatability (RSD = 12%) of the undiluted smoke generated by the Borgwaldt RM20S(®) was assessed by quantifying solanesol using high-performance liquid chromatography with ultraviolet detection (HPLC/UV). Finally, the repeatability (r between 0.98 and 4.53 and RSD between 8.8% and 12%) of the dilution of generated smoke particulate phase was assessed by quantifying solanesol following various dilutions of cigarette smoke. The findings in this study suggest the Borgwaldt RM20S(®) smoking machine is a reliable tool to generate and deliver repeatable and reproducible doses of whole smoke to in vitro cultures.

Isradipine antagonizes hypobaric hypoxia induced CA1 damage and memory impairment: Complementary roles of L-type calcium channel and NMDA receptors.

Hypobaric hypoxia leads to cognitive dysfunctions due to increase in intracellular calcium through ion channels. The purpose of this study was to examine the temporal contribution of L-type calcium channels and N-methyl-D-aspartate receptors (NMDARs) in mediating neuronal death in male Sprague Dawley rats exposed to hypobaric hypoxia simulating an altitude of 25,000 ft for different durations. Decreasing exogenous calcium loads by blocking voltage-gated calcium influx with isradipine (2.5 mg kg(-1)), and its efficacy in providing neuroprotection and preventing memory impairment following hypoxic exposure was also investigated. Effect of isradipine on calcium-dependent enzymes mediating oxidative stress and apoptotic cell death was also studied. Blocking of L-type calcium channels with isradipine reduced hypoxia-induced activation of calcium dependent xanthine oxidases, monoamine oxidases, cytosolic phospholipase A(2) and cycloxygenases (COX-2) along with concomitant decrease in free radical generation and cytochrome c release. Increased expression of calpain and caspase 3 was also observed following exposure to hypobaric hypoxia along with augmented neurodegeneration and memory impairment which was adequately prevented by isradipine administration. Administration of isradipine during hypoxic exposure protected the hippocampal neurons following 3 and 7 days of exposure to hypobaric hypoxia along with improvement in spatial memory.

Generation and characterization of gasoline engine exhaust inhalation exposure atmospheres.

Exposure atmospheres for a rodent inhalation toxicology study were generated from the exhaust of a 4.3-L gasoline engine coupled to a dynamometer and operated on an adapted California Unified Driving Cycle. Exposure levels were maintained at three different dilution rates. One chamber at the lowest dilution had particles removed by filtration. Each exposure atmosphere was characterized for particle mass, particle number, particle size distribution, and detailed chemical speciation. The majority of the mass in the exposure atmospheres was gaseous carbon monoxide, nitrogen oxides, and volatile organics, with small amounts of particle-bound carbon/ions and metals. The atmospheres varied according to the cycle, with the largest spikes in volatile organic and inorganic species shown during the "cold start" portion of the cycle. Ammonia present from the exhaust and rodents interacted with the gasoline exhaust to form secondary inorganic particles, and an increase in exhaust resulted in higher proportions of secondary inorganics as a portion of the total particle mass. Particle size had a median of 10-20 nm by number and approximately 150 nm by mass. Volatile organics matched the composition of the fuel, with large proportions of aliphatic and aromatic hydrocarbons coupled to low amounts of oxygenated organics. A new measurement technique revealed organics reacting with nitrogen oxides have likely resulted in measurement bias in previous studies of combustion emissions. Identified and measured particle organic species accounted for about 10% of total organic particle mass and were mostly aliphatic acids and polycyclic aromatic hydrocarbons.

Ear pain and its treatment in hypobaric chamber training in the Japan Air Self-Defense Force.

BACKGROUND: We have documented that ear pain is the most prevalent physiologic incident during hypobaric chamber training in the Japan Air Self-Defense Force. Ear pain may increase also in flight in the future because it is closely related to allergic rhinitis. Therefore, it is very important to know the characteristic of ear pain and the efficacy of its treatment. METHODS: The incidence of ear pain was calculated in each training profile from 1990 to 1998. Type III chamber flight records were further analyzed for the characteristics of ear pain: relationship with a trainee occupational category, time of occurrence of ear pain, and efficacy of treatment. RESULTS: Of 17,935 exposures, 740 trainees (4.1%) had ear pain. Of 7,047 trainees, 429 (6.1%) complained of ear pain especially in Type III, totaling 625 times. Fighter pilots and cargo pilots complained of ear pain one twelfth and one third the number of times, respectively, compared with passengers. Of the 625 episodes, 616 (98.6%) occurred during descent. Three kinds of treatment were administered until the pain was relieved in the following order: Valsalva maneuver, Politzer bag, and decompression. The efficacy rates were 35.8, 92.3, and 83.9%, respectively. Only 5 trainees (0.07%) could not complete training due to ear pain despite treatment. CONCLUSION: The combination treatment of Valsalva maneuver, Politzer bag, and decompression is very effective for relieving ear pain encountered during hypobaric chamber training. A health specialist needs to understand ear pain and its treatment in hypobaric environment such as aircraft.

Prohibition of artificial hypoxic environments in sports: health risks rather than ethics.

There is actual debate on a recent position of the World Anti-Doping Agency (WADA), which has cautiously refrained from banning hypoxic tents and intends to monitor their health risk. Regardless of teleological and deontological concepts, we highlight that the health risks inherent to the widespread use of these artificial performance-enhancing devices would make them as unsafe as other forms of blood doping.

Comparison of high MRI T1 signals with manganese concentration in brains of cynomolgus monkeys after 8 months of stainless steel welding-fume exposure.

Several pharmacokinetic studies on inhalation exposure to manganese (Mn) have already demonstrated that Mn readily accumulates in the olfactory and brain regions. However, a shortening of the magnetic resonance imaging (MRI) T1 relaxation time or high T1 signal intensity in specific sites of the brain, including the globus pallidus and subcortical frontal white matter, as indicative of tissue manganese accumulation has not yet been clearly established for certain durations of known doses of welding-fume exposure in experimental animals. Accordingly, to investigate the movement of manganese after welding-fume exposure, six cynomolgus monkeys were acclimated and assigned to three dose groups: unexposed, low dose (31 mg/m(3) total suspended particulate [TSP], 0.9 mg/m(3) of Mn), and high dose (62 mg/m(3) TSP, 1.95 mg/m(3) of Mn) of total suspended particulate. The primates were exposed to manual metal arc stainless steel (MMA-SS) welding fumes for 2 h per day in an inhalation chamber system equipped with an automatic fume generator. Magnetic resonance imaging (MRI) studies were conducted before the initiation of exposure and thereafter every month. The tissue Mn concentrations were then measured after a plateau was reached regarding the shortening of the MRI T1 relaxation time. A dose-dependent increase in the Mn concentration was found in the lungs, while noticeable increases in the Mn concentrations were found in certain tissues, such as the liver, kidneys, and testes. Slight increases in the Mn concentrations were found in the caudate, putamen, frontal lobe, and substantia nigra, while a dose-dependent noticeable increase was only found in the globus pallidus. Therefore, the present results indicated that a shortening of the MRI T1 relaxation time corresponded well with the Mn concentration in the globus pallidus after prolonged welding-fume exposure.

The controlled-environment chamber: a new mouse model of dry eye.

PURPOSE: To develop a controlled-environment chamber (CEC) for mice and verify the effects of a low-humidity setting on ocular surface signs in normal mice. METHODS: Eight- to 12-week-old BALB/c mice were used in a controlled-environment chamber (CEC) where relative humidity (RH), temperature (T), and airflow (AF) are regulated and monitored. Mice were placed into the CEC and exposed to specific environmentally controlled conditions (RH = 18.5% +/- 5.1%, AF = 15 L/min, T = 21-23 degrees C) for 3, 7, 14, and 28 days. Control mice were kept in a normal environment (RH = 50%-80%, no AF, T = 21-23 degrees C) for the same duration. Aqueous tear production by means of the cotton thread test, corneal fluorescein staining (score, 0-15), and goblet cell density in the superior and inferior conjunctiva were measured by a masked observer. RESULTS: No statistically significant differences between the groups were found at baseline. Decreased tear secretion and increased corneal fluorescein staining were significantly present on day 3, 7, 14, and 28 in animals kept in the CEC. Goblet cell density was significantly decreased in the superior conjunctiva on day 7, and on day 3, 7, and 14 in the inferior conjunctiva in the CEC-kept mice compared with control animals. CONCLUSIONS: This study indicates that exposure of normal mice to a low-humidity environment in a CEC can lead to significant alterations in tear secretion, goblet cell density, and acquisition of dry eye-related ocular surface signs.

Platelet-activating factor receptor-deficient mice are protected from experimental sleep apnea-induced learning deficits.

Intermittent hypoxia (IH) during sleep, a hallmark of sleep apnea, is associated with neurobehavioral impairments, regional neurodegeneration and increased oxidative stress and inflammation in rodents. Platelet-activating factor (PAF) is an important mediator of both normal neural plasticity and brain injury. We report that mice deficient in the cell surface receptor for PAF (PAFR-/-), a bioactive mediator of oxidative stress and inflammation, are protected from the spatial reference learning deficits associated with IH. Furthermore, PAFR-/- exhibit attenuated elevations in inflammatory signaling (cyclo-oxygenase-2 and inducible nitric oxide synthase activities), degradation of the ubiquitin-proteasome pathway and apoptosis observed in wild-type littermates (PAFR+/+) exposed to IH. Collectively, these findings indicate that inflammatory signaling and neurobehavioral impairments induced by IH are mediated through PAF receptors.