The atmospheric environment—an introduction

The atmosphere is part of the environment with which the human organism is permanently confronted. Epidemiological research investigates the occurrence of effects on morbidity and mortality due to heat, cold, air pollution and changes in the weather. Concentrating on aspects of the environment relevant for medical questions, three major complexes of effects can be discriminated: the complex conditions of heat exchange, the direct biological effects of solar radiation, and air pollution. Biometeorological knowledge can serve to assess the atmospheric environment, and can also be of help in the field of preventive planning, to conserve and develop the climate as a natural resource with regard to man's health, well-being and performance.     

Stress and putative endogenous ligands for benzodiazepine receptors: the importance of characteristics of the aversive situation and of differential emotionality in experimental animals.

The relationships between anxiety/stress, possible endogenous ligands for benzodiazepine receptors and the behavioral modification by drugs are discussed in this short review, including the specific characteristics of elements involved in those interactions, e.g. ones concerning the aversiveness of the stressful situation and the nature of the organism under investigation. These are important factors when considering aversive tasks, insofar as they may involve stressful conditions which differ in intensity and in the degree of control afforded the subject. These characteristics may well lead to differing functional effects on GABA-gated chloride channels or, in other words, to an incongruous balance between endogenous benzodiazepine receptor agonist and inverse agonist activity. This is not surprising, as it is well known that different forms of stressors often actually produce divergent behavioral, physiological and biochemical effects. This review also illustrates the necessity of taking into account the variable effects of stressors and/or drugs on animals differing in reactivity or emotionality, even in the case of 'non-selected' stocks. The implication is made that, by genetic and/or environmental manipulation of the emotional state of the animals used, it will be possible to obtain more clearly definable results in neuropharmacological and psychopharmacological studies.     

Melatonin and circadian control in mammals

Summary Although pinealectomy has little influence on the circadian locomotor rhythms of laboratory rats, administration of the pineal hormone melatonin has profound effects. Evidence for this comes from studies in which pharmacological doses of melatonin are administered under conditions of external desynchronization, internal desynchronization, steady state light-dark conditions, and phase shifts of the zeitgeber. Taken together with recent findings on melatonin receptor concentration in the rat hypothalamus, particularly at the level of the suprachiasmatic nuclei, these results suggest that melatonin is a potent synchronizer of rat circadian rhythms and has a direct action on the circadian pacemaker. It is possible, therefore, that the natural role of endogenous melatonin is to act as an internal zeitgeber for the total circadian structure of mammals at the level of cell, tissue, organ, whole organism and interaction of that organism with environmental photoperiod changes.     

Melatonin and circadian control in mammals

Although pinealectomy has little influence on the circadian locomotor rhythms of laboratory rats, administration of the pineal hormone melatonin has profound effects. Evidence for this comes from studies in which pharmacological doses of melatonin are administered under conditions of external desynchronization, internal desynchronization, steady state light-dark conditions, and phase shifts of the zeitgeber. Taken together with recent findings on melatonin receptor concentration in the rat hypothalamus, particularly at the level of the suprachiasmatic nuclei, these results suggest that melatonin is a potent synchronizer of rat circadian rhythms and has a direct action on the circadian pacemaker. It is possible, therefore, that the natural role of endogenous melatonin is to act as an internal zeitgeber for the total circadian structure of mammals at the level of cell, tissue, organ, whole organism and interaction of that organism with environmental photoperiod changes.     

Stress and putative endogenous ligands for benzodiazepine receptors: The importance of characteristics of the aversive situation and of differential emotionality in experimental animals

The relationships between anxiety/stress, possible endogenous ligands for benzodiazepine receptors and the behavioral modification by drugs are discussed in this short review, including the specific characteristics of elements involved in those interactions, e.g. ones concerning the aversiveness of the stressful situation and the nature of the organism under investigation. These are important factors when considering aversive tasks, insofar as they may involve stressful conditions which differ in intensity and in the degree of control afforded the subject. These characteristics may well lead to differing functional effects on GABA-gated chloride channels or, in other words, to an incongruous balance between endogenous benzodiazepine receptor agonist and inverse agonist activity. This is not surprising, as it is well known that different forms of stressors often actually produce divergent behavioral, physiological and biochemical effects. This review also illustrates the necessity of taking into account the variable effects of stressors and/or drugs on animals differing in reactivity or emotionality, even in the case of non-selected stocks. The implication is made that, by genetic and/or environmental manipulation of the emotional state of the animals used, it will be possible to obtain more clearly definable results in neuropharmacological and psychopharmacological studies.     

Biological responses inCaenorhabditis elegans to high magnetic fields

Here we describe a device for testing possible influences of high magnetic fields on biological processes, by which alternating-current magnetic stimuli as high as 1.7 T can be administered. Experiments with a simple multicellular organism, the nematodeCaenorhabditis elegans, revealed that intermittent exposure to the magnetic fields modestly inhibited the animal's reproduction as well as its post-embryonic development, and caused a marked but transient derangement in its locomotory behavior. Available evidence indicates that alternating high magnetic fields can elicit both chronic and acute biological effects, but that the effects may be well tolerated or compensated for by the living organism.     

Erythropoietin modulates the neural control of hypoxic ventilation

Numerous factors involved in general homeostasis are able to modulate ventilation. Classically, this comprises several kind of molecules, including neurotransmitters and steroids that are necessary for fine tuning ventilation under different conditions such as sleep, exercise, and acclimatization to high altitude. Recently, however, we have found that erythropoietin (Epo), the main regulator of red blood cell production, influences both central (brainstem) and peripheral (carotid bodies) respiratory centers when the organism is exposed to hypoxic conditions. Here, we summarize the effect of Epo on the respiratory control in mammals and highlight the potential implication of Epo in the ventilatory acclimatization to high altitude, as well as in the several respiratory sickness and syndromes occurring at low and high altitude. (Part of a multi-author review.)     

Effects of isoxazolyl-naphthoquinoneimines on growth and oxygen radical production in Trypanosoma cruzi and Crithidia fasciculata

Several 4-(aminomethylisoxazolyl)-1,2-naphthoquinones inhibited growth and DNA synthesis in Trypanosoma cruzi and stimulated O2 uptake and O2-. generation by the parasite epimastigotes and their mitochondrial and microsomal membranes; these results support the idea that oxygen radicals play a role in quinone toxicity. Maximal effects on respiration and O2-. generation were observed with antimycin-inhibited cells. Similar results as well as stimulation of H2O2 production were obtained with Crithidia fasciculata despite the presence of catalase in this organism.     

Retroelements and their impact on genome evolution and functioning

Retroelements comprise a considerable fraction of eukaryotic genomes. Since their initial discovery by Barbara McClintock in maize DNA, retroelements have been found in genomes of almost all organisms. First considered as a “junk DNA” or genomic parasites, they were shown to influence genome functioning and to promote genetic innovations. For this reason, they were suggested as an important creative force in the genome evolution and adaptation of an organism to altered environmental conditions. In this review, we summarize the up-to-date knowledge of different ways of retroelement involvement in structural and functional evolution of genes and genomes, as well as the mechanisms generated by cells to control their retrotransposition.     

The Gaia hypothesis: A fruitful fallacy?

Summary In 1968, Lovelock proposed that the Earth's biosphere, atmosphere, oceans, and soils form a single living organism, which he called Gaia after the Greek Earth goddess. This entity constitutes a feedback system which supposedly seeks an optimal physical and chemical environment for life on Earth. Most scientists accept a weaker version of the hypothesis, that life has had a tremendous impact on the physical environment. They reject the strong version on the basis that planetary self-regulation would need foresight and planning by living organisms, which is incompatible with natural selection. Lovelock subsequently proposed a simple computer model, called Daisyworld, which shows that, under certain conditions, feedback systems without foresight can stabilize external inputs. The main value of the Gaia hypothesis lies in its holistic perspective, which is needed to avoid environmentally undesirable, cumulative effects of small decisions.     

Failure of coffee to inhibit the pharmacodynamic activity of morphine in vivo

High doses of caffeine-containing as well as decaffeinated instant coffee neither inhibited morphine-induced analgesia in mice nor the morphine-induced fall of blood pressure, heart rate and respiratory rate in rats. On the contrary, caffeine-containing coffee even enhanced the analgesic effects of morphine in mice. Coffee thus does not exhibit opiate-antagonizing activity in the whole organism in vivo. The very weak morphine-antagonistic efficacy of coffee powder in the myenteric plexus-longitudinal muscle preparation from the guinea pig ileum is of no practical importance.     

Failure of coffee to inhibit the pharmacodynamic activity of morphine in vivo

Summary High doses of caffeine-containing as well as decaffeinated instant coffee neither inhibited morphine-induced analgesia in mice nor the morphine-induced fall of blood pressure, heart rate and respiratory rate in rats. On the contrary, caffeine-containing coffee even enhanced the analgesic effects of morphine in mice. Coffee thus does not exhibit opiate-antagonizing activity in the whole organism in vivo. The very weak morphine-antagonistic efficacy of coffee powder in the myenteric plexus-longitudinal muscle preparation from the guinea pig ileum is of no practical importance.     

Fibroblast growth factor 21: an overview from a clinical perspective

Fibroblast growth factor 21 (FGF21) has been proposed as a novel putative therapeutic agent in type 2 diabetes. A large amount of data, predominantly obtained from murine models but also from non-human primates, suggest that FGF21 ameliorates obesity-associated hyperglycemia and hyperlipidemia primarily via effects on adipose tissue and the pancreas. In addition, FGF21 has been reported to play a pivotal regulatory role in starvation and ketosis. However, while it is clear that FGF21 has potent effects in vivo in several animal models, the exact mechanisms remain elusive. Moreover, very recent results from different human cohort studies have shown a paradoxical regulation of plasma FGF21 in obesity and type 2 diabetes as well as other important qualitative differences in the effects and regulation of FGF21 between rodents and humans. This review focuses on the most recently published data on FGF21 with emphasis on results obtained in humans.     

Urban bioclimatology

This article deals with the part of urban climatology which is of particular relevance to human beings. Presented first is a summary of all human biometeorologically effective complexes, as well as other factors which are relevant to urban planning and which depend on atmospheric conditions in urban structures in a direct or indirect manner. Later, methods for human biometeorologically significant assessment of thermal and air pollution components of the urban climate are discussed in detail, because these components can be strongly influenced by urban planning. The application of these methods is illustrated by some results of appropriate investigations in urban areas.     

Cellular senescence: a view throughout organismal life

Cellular senescence is the final fate of most cells in response to specific stimuli, but is not the end. Indeed, it is the beginning of a singular life, with multiple side roads leading to diverse effects on the organism. Many studies have been done in the last few years to elucidate the intriguing role of senescent cells in the organism, demonstrating them as the cause of several age-related diseases. However, these cells are also positively implicated in other important pathways, such as embryogenesis and wound healing. It appears that the multiple effects are time-dependent: long-term senescence is mostly implicated in chronic inflammation and disease, whereas in the short term, senescent cells seem to be beneficial, being rapidly targeted by the innate immune system. The influence of senescent cells on their neighbors by paracrine factors, differential activity depending on developmental stage, and duration of the effects make the cellular senescent program a unique spatial–temporal mechanism. During pathological conditions such as progeroid syndromes, this mechanism is deregulated, leading to accelerated onset of some aging-related diseases and a shorter lifespan, among other physiological defects. Here, we review the three primary cell senescence programs described so far (replicative, stress-induced, and developmentally programmed senescence), their onset during development, and their potential roles in diseases with premature aging. Finally, we discuss the role of immune cells in keeping senescence burden below the threshold of disease.     

VEGF ligands and receptors: implications in neurodevelopment and neurodegeneration

Intensive research in the last decade shows that the prototypic angiogenic factor vascular endothelial growth factor (VEGF) can have direct effects in neurons and modulate processes such as neuronal migration, axon outgrowth, axon guidance and neuronal survival. Depending on the neuronal cell type and the process, VEGF seems to exert these effects by signaling via different receptors. It is also becoming clear that other VEGF ligands such as VEGF-B, -C and -D can act in various neuronal cell types as well. Moreover, apart from playing a role in physiological conditions, VEGF and VEGF-B have been related to different neurological disorders. We give an update on how VEGF controls different processes during neurodevelopment as well as on its role in several neurodegenerative disorders. We also discuss recent findings demonstrating that other VEGF ligands influence processes such as neurogenesis and dendrite arborization and participate in neurodegeneration.     

Severe weather event attribution: Why values won't go away

We start by reviewing the complicated situation in methods of scientific attribution of climate change to extreme weather events. We emphasize the social values involved in using both so-called ″storyline″ and ordinary probabilistic or ″risk-based″ methods, noting that one important virtue claimed by the storyline approach is that it features a reduction in false negative results, which has much social and ethical merit, according to its advocates. This merit is critiqued by the probabilistic, risk-based, opponents, who claim the high ground; the usual probabilistic approach is claimed to be more objective and more ″scientific″, under the grounds that it reduces false positive error. We examine this mostly-implicit debate about error, which apparently mirrors the old Jeffrey-Rudner debate. We also argue that there is an overlooked component to the role of values in science: that of second-order inductive risk, and that it makes the relative role of values in the two methods different from what it first appears to be. In fact, neither method helps us to escape social values, and be more scientifically ″objective″ in the sense of being removed or detached from human values and interests. The probabilistic approach does not succeed in doing so, contrary to the claims of its proponents. This is important to understand, because neither method is, fundamentally, a successful strategy for climate scientists to avoid making value judgments.     

Molecular mechanisms of melatonin’s inhibitory actions on breast cancers

Melatonin is involved in many physiological functions and it plays an important role in many pathological processes as well. Melatonin has been shown to reduce the incidence of experimentally induced cancers and can significantly inhibit the growth of some human tumors, namely hormone-dependent cancers. The anticancer effects of melatonin have been observed in breast cancer, both in in vivo with models of chemically induced rat mammary tumors, and in vitro studies on human breast cancer cell lines. Melatonin acts at different physiological levels and its antitumoral properties are supported by a set of complex, different mechanisms of action, involving apoptosis activation, inhibition of proliferation, and cell differentiation.     

Die teratogene Wirkung von Äthylharnstoff und Nitrit bei Ratten

Summary Simultaneous peroral application of ethylurea and sodium nitrite to pregnant Sprague-Dawley rats, on the 9th and 10th days of gestation, causes embryotoxic and/or teratogenic effects. Each substance alone does not afflict the fetuses, whereas the combined addition to the food permits the formation of ethyl nitroso-urea in the digestive tract. The latter readily passes the placenta and develops the teratogenic effect. It is to be considered that teratogenic substances can occur from food constituents in the human organism also.