Influence of hydration and airflow on thermoregulatory control in the heat

Exercise-heat exposure results in significant sweat losses due to large biophysical requirements for evaporative heat loss. Progressive body water losses will increase plasma tonicity and decrease blood volume (hypertonic–hypovolemia). The result is reduced dry and evaporative heat exchange through alterations in the core temperature threshold for initiation of skin blood flow and sweating as well as changes in the sensitivity of these thermo-effectors. Regulation of reduced sweating conserves body water, which reduces heat loss and increases exercise hyperthermia, but the magnitude of this effect is modified by environmental heat transfer capabilities. The focus of this paper is to (1) examine the major mechanisms by which hypohydration alters thermoregulatory responses in the heat, and (2) illustrate how important differences in environmental airflow characteristics between laboratory and field settings may modify these effects.     

Chronic unpredictable stress (CUS) enhances the carcinogenic potential of 7,12-dimethylbenz(a)anthracene (DMBA) and accelerates the onset of tumor development in Swiss albino mice

Social stressors evolving from individual and population interactions produce stress reactions in many organisms (including humans), influencing homeostasis, altering the activity of the immunological system, and thus leading to various pathological states including cancer and their progression. The present study sought to validate the effectiveness of chronic unpredictable stress (CUS) in cancer promotion and to assess oxidative stress outcomes in terms of various in vivo biochemical parameters, oxidative stress markers, DNA damage, and the development of skin tumors in Swiss albino mice. Animals were randomized into different groups based on their exposure to CUS alone, 7,12-dimethylbenz(a)anthracene (DMBA) alone (topical), and DMBA-12-O-tetradecanoylphorbol-13-acetate (TPA) (topical) and exposure to CUS prior to DMBA or DMBA-TPA treatments and sacrificed after 16 weeks of treatment. Prior exposure to CUS significantly increased the pro-oxidant effect of carcinogen, depicted by compromised levels of antioxidants in the circulation and skin, accompanied by enhanced lipid peroxidation, plasma corticosterone, and marker enzymes as compared to DMBA-alone or DMBA-TPA treatments. DNA damage results corroborated the above biochemical outcomes. Also, the development of skin tumors (in terms of their incidence, tumor yield, and tumor burden) in mice in the presence and absence of stress further strongly supported our above biochemical measurements. CUS may work as a promoter of carcinogenesis by enhancing the pro-oxidant potential of carcinogens. Further studies may be aimed at the development of interventions for disease prevention by identifying the relations between psychological factors and DNA damage.     

An open-loop model for investigating mammalian thermosensitivity

We have developed, and herein describe, a simple, open-loop model in the rat, in which both skin and hypothalamic temperatures can be modified and clamped. A water-perfused thermode was positioned in the abdomen to drive hypothalamic temperature, and a water-perfused jacket was used to clamp skin temperature. These permitted the independent control of hypothalamic and skin temperatures. The former could be altered between 35 and 41 °C whilst achieving an isothermal skin temperature clamp. Similarly, skin temperature could be modified between 22 and 42 °C whilst hypothalamic temperature was clamped. Maximal hypothalamic heating and cooling rates were: 0.75 and −2.04 °C h⁻¹ 100 g⁻¹. We are currently using this animal model to investigate how central thermosensitivity is affected via manipulations of hypothalamic cooling rates.     

Differences in pigment-containing organelles between color forms of the red-backed salamander,Plethodon cinereus

Summary Chromatophores of two color forms of the salamander, Plethodon cinereus were studied by electron microscopy. Erythrophores found in the red-backed form possess pterinosomes, some with regions of high electron density. In addition, a few melanosome-like organelles are present. On the other hand, the lead-backed form displays no visible erythrophores but instead melanophores with melanosomes being the most prevalent organelle and a few pterinosomes. The possibility that this represents a kind of hybrid chromatophore with intermediate stages in melanosome-pterinosome interconversion is discussed.This study was supported in part by GB-8347 from the National Science Foundation.Contribution No. 255, Department of Biology, Wayne State University.     

Protein oxidation,UVA and human DNA repair

Solar UVB is carcinogenic. Nucleotide excision repair (NER) counteracts the carcinogenicity of UVB by excising potentially mutagenic UVB-induced DNA lesions. Despite this capacity for DNA repair, non-melanoma skin cancers and apparently normal sun-exposed skin contain huge numbers of mutations that are mostly attributable to unrepaired UVB-induced DNA lesions. UVA is about 20-times more abundant than UVB in incident sunlight. It does cause some DNA damage but this does not fully account for its biological impact. The effects of solar UVA are mediated by its interactions with cellular photosensitizers that generate reactive oxygen species (ROS) and induce oxidative stress. The proteome is a significant target for damage by UVA-induced ROS. In cultured human cells, UVA-induced oxidation of DNA repair proteins inhibits DNA repair. This article addresses the possible role of oxidative stress and protein oxidation in determining DNA repair efficiency – with particular reference to NER and skin cancer risk.     

New insight into phase behavior and permeability of skin lipid models based on sphingosine and phytosphingosine ceramides

The intercellular lipid matrix of the stratum corneum (SC), which consist mainly of ceramides (CERs), free fatty acids and cholesterol, is fundamental to the skin barrier function. These lipids assemble into two lamellar phases, known as the long and short periodicity phases (LPP and SPP respectively). The LPP is unique in the SC and is considered important for the skin barrier function. Alterations in CER composition, as well as impaired skin barrier function, are commonly observed in diseased skin, yet the understanding of this relationship remains insufficient. In this study, we have investigated the influence of non-hydroxy and α-hydroxy sphingosine-based CERs and their phytosphingosine counterparts on the permeability and lipid organization of model membranes, which were adjusted in composition to enhance formation of the LPP. The permeability was compared by diffusion studies using ethyl-p-aminobenzoate as a model drug, and the lipid organization was characterized by X-ray diffraction and infrared spectroscopy. Both the sphingosine- and phytosphingosine-based CER models formed the LPP, while the latter exhibited a longer LPP repeat distance. The ethyl-p-aminobenzoate flux across the sphingosine-based CER models was higher when compared to the phytosphingosine counterparts, contrary to the fact that the α-hydroxy phytosphingosine-based CER model had the lowest chain packing density. The unanticipated low permeability of the α-hydroxy phytosphingosine-based model is probably associated with a stronger headgroup hydrogen bonding network. Our findings indicate that the increased level of sphingosine-based CERs at the expense of phytosphingosine-based CERs, as observed in the diseased skin, may contribute to the barrier function impairment.     

Organization of DNA damage,excision repair,and mutagenesis in chromatin: A genomic perspective

Genomic DNA is constantly assaulted by both endogenous and exogenous damaging agents. The resulting DNA damage, if left unrepaired, can interfere with DNA replication and be converted into mutations. Genomic DNA is packaged into a highly compact yet dynamic chromatin structure, in order to fit into the limited space available in the nucleus of eukaryotic cells. This hierarchical chromatin organization serves as both the target of DNA damaging agents and the context for DNA repair enzymes. Biochemical studies have suggested that both the formation and repair of DNA damage are significantly modulated by chromatin. Our understanding of the impact of chromatin on damage and repair has been significantly enhanced by recent studies. We focus on the nucleosome, the primary building block of chromatin, and discuss how the intrinsic structural properties of nucleosomes, and their associated epigenetic modifications, affect damage formation and DNA repair, as well as subsequent mutagenesis in cancer.     

Effects of benfluorex-vitamin C supplementation on cutaneous capillaries of diabetic rats

The ultrastructural changes on capillaries of the dermis in diabetic and benfluorex-vitamin C treated diabetic rats have been investigated. Three groups of 21 Wistar albino rats were used in the examination: control, diabetes, and benfluorex-vitamin C treated diabetic rats. Diabetes was induced by injection of streptozotocin. The streptozotocin-induced group was treated for 21 days with vitamin C and benfluorex, of which antidiabetic and antihyperlipidemic effects were experimentally proved. Samples taken from the skin of rats' legs were examined under transmission electron microscopy. Swollen endothelial cells, narrowed capillary lumens, a thickened basement membrane, and fusion of mitochondrial cristae in the capillaries of diabetic rat dermis were seen. In the benfluorex-vitamin C treated group, contrary to the diabetic group, neither signs of degeneration in endothelial cells nor a significant difference with the control group with regard to capillary structure were observed. Amelioration in capillaries appears to be due to benfluorex and vitamin C treatment in diabetes.