Neuropeptide and Small Transmitter Coexistence: Fundamental Studies and Relevance to Mental Illness.

Neuropeptides are auxiliary messenger molecules that always co-exist in nerve cells with one or more small molecule (classic) neurotransmitters. Neuropeptides act both as transmitters and trophic factors, and play a role particularly when the nervous system is challenged, as by injury, pain or stress. Here neuropeptides and coexistence in mammals are reviewed, but with special focus on the 29/30 amino acid galanin and its three receptors GalR1, -R2 and -R3. In particular, galanin's role as a co-transmitter in both rodent and human noradrenergic locus coeruleus (LC) neurons is addressed. Extensive experimental animal data strongly suggest a role for the galanin system in depression-like behavior. The translational potential of these results was tested by studying the galanin system in postmortem human brains, first in normal brains, and then in a comparison of five regions of brains obtained from depressed people who committed suicide, and from matched controls. The distribution of galanin and the four galanin system transcripts in the normal human brain was determined, and selective and parallel changes in levels of transcripts and DNA methylation for galanin and its three receptors were assessed in depressed patients who committed suicide: upregulation of transcripts, e.g., for galanin and GalR3 in LC, paralleled by a decrease in DNA methylation, suggesting involvement of epigenetic mechanisms. It is hypothesized that, when exposed to severe stress, the noradrenergic LC neurons fire in bursts and release galanin from their soma/dendrites. Galanin then acts on somato-dendritic, inhibitory galanin autoreceptors, opening potassium channels and inhibiting firing. The purpose of these autoreceptors is to act as a 'brake' to prevent overexcitation, a brake that is also part of resilience to stress that protects against depression. Depression then arises when the inhibition is too strong and long lasting - a maladaption, allostatic load, leading to depletion of NA levels in the forebrain. It is suggested that disinhibition by a galanin antagonist may have antidepressant activity by restoring forebrain NA levels. A role of galanin in depression is also supported by a recent candidate gene study, showing that variants in genes for galanin and its three receptors confer increased risk of depression and anxiety in people who experienced childhood adversity or recent negative life events. In summary, galanin, a neuropeptide coexisting in LC neurons, may participate in the mechanism underlying resilience against a serious and common disorder, MDD. Existing and further results may lead to an increased understanding of how this illness develops, which in turn could provide a basis for its treatment.

Investigation of an outbreak of cercarial dermatitis.

We present the investigation of an outbreak of cercarial dermatitis that occurred in a recreational-tourist lake in the Quebec City region (Canada) in the summer of 1999. A case-reporting form was sent to 450 families likely to have activities that would bring them in contact with the lake's water. The snails were characterized and the prevalence of their infestation by schistosomes was investigated. In total, 63 episodes consistent with cercarial dermatitis were reported. Sixty-nine percent of the cases occurred from swimming at the same beach. This location was the one where the only population of snails in the lake was identified. Shoreline residents were informed that they should not feed waterfowl, and a clean-up of the snail population was done at the start of the following summer. There were no cases of cercarial dermatitis at this site the following summer.

Wood-burning appliances and indoor air quality.

Wood heating represents an interesting economic alternative to electrical or heating oil and gas systems. However, many people are concerned about poor indoor air quality in homes equipped with wood-burning appliances. We conducted a study in the Quebec City region (Canada) to verify the extent of indoor air contamination, and to examine the frequency of respiratory symptoms and illnesses among occupants of wood-heated homes. One child attending primary school (median = 8 years old; range = 5-14 years old) and an adult (median = 37 years old; range = 23-52 years old) were recruited in each eligible house. Eligible houses were without known sources of combustion products (smokers, attached garage, oil or gas furnace, gas stove, etc.) except for wood-burning appliance. Out of the 89 houses included in the study, 59 had wood-burning appliances. Formaldehyde, nitrogen dioxide, respirable particles (PM10) and carbon monoxide were measured in a sub-set of 49 houses (41 with a wood-burning appliance and 8 without). The frequency of respiratory symptoms and diseases among participants were documented using a daily symptom diary. Concentrations of contaminants were low in most houses, both with or without a wood-burning appliance. Globally, there was no consistent relationship between the presence of a wood-burning appliance and respiratory morbidity in residents. Nevertheless, residents who mentioned being exposed to fumes emitted by such an appliance reported more respiratory illnesses and symptoms. The presence of animals or molds, and keeping windows closed most of the time in winter were other factors associated with respiratory problems. We conclude that wood burning appears to be a respiratory health risk for occupants if the appliance is not maintained and used properly.

Air quality monitoring during indoor Monster Truck and car demolition shows.

This article describes the results of air quality monitoring in an indoor ice skating rink during three Monster Truck and car demolition exhibitions, and the public health study that was carried out. The exposure of the people present to carbon monoxide and nitrogen dioxide was continuously monitored in order to determine the time-weighted average concentrations and the maximum peaks. Nitrogen dioxide concentrations were generally under the limit of detection of the device (0.5 ppm). However, carbon monoxide levels exceeded standards for workers. Maximum time-weighted average concentrations during the exhibitions were 100 parts per million with several peaks exceeding 200 parts per million (maximum value: 1600 parts per million). Recommendations were made and during a subsequent event, the carbon monoxide concentrations were reduced to protect health. Indoor exhibitions of motorized vehicles generate significant amounts of combustion gases, which can be a health hazard. There must be sufficient ventilation and the carbon monoxide and nitrogen dioxide concentrations must be monitored. In addition, the motors of the most polluting vehicles should be adjusted before the events in order to limit the emission of combustion products. If these steps are not met, the events should be held outdoors.

An unusual case of carbon monoxide poisoning.

Carbon monoxide, a gas originating from incomplete combustion of carbon-based fuels, is an important cause of human deaths. In this paper, we describe an unusual carbon monoxide poisoning in a dwelling without obvious sources of combustion gases, for which two adults had to be treated in a hyperbaric chamber. Carbon monoxide readings were taken in the house and in the neighboring homes. Methane gas and nitrogen oxide levels were also monitored in the house air. Soil samples were collected around the house and tested for hydrocarbon residues. The investigation revealed the presence of a pocket of carbon monoxide under the foundation of the house. The first readings revealed carbon monoxide levels of 500 ppm in the basement. The contamination lasted for a week. The investigation indicated that the probable source of contamination was the use of explosives at a nearby rain sewer construction site. The use of explosives in a residential area can constitute a major source of carbon monoxide for the neighboring populations. This must be investigated, and public health authorities, primary-care physicians, governmental authorities, and users and manufacturers of explosives must be made aware of this problem.

Molecular confirmation of hepatitis A virus from well water: epidemiology and public health implications.

An outbreak of hepatitis A in a rural river-island community was found to be associated with consumption of contaminated well water. Specimens from case-patients, the implicated well, and a cesspool suspected to be the source of contamination were all positive for hepatitis A virus (HAV) RNA by immunocapture reverse-transcription polymerase chain reaction. All isolates were identical over about 400 bases from two capsid-encoding regions of the genome, identifying the chain of transmission. Other wells up to 60 m from the cesspool also contained HAV RNA. In addition, HAV RNA was detected in the contamination source well 6 months after the initial contamination, when fecal coliform bacteria were no longer present. These findings demonstrate the utility of viral detection techniques to evaluate contaminated ground water.