Host-defense peptides of the skin with therapeutic potential: From hagfish to human

It is now well established that peptides that were first identified on the basis of their ability to inhibit growth of bacteria and fungi are multifunctional and so are more informatively described as host-defense peptides. In some cases, their role in protecting the organism against pathogenic microorganisms, although of importance, may be secondary. A previous article in the journal (Peptides 2014; 57:67–77) assessed the potential of peptides present in the skin secretions of frogs for development into anticancer, antiviral, immunomodulatory and antidiabetic drugs. This review aims to extend the scope of this earlier article by focusing upon therapeutic applications of host-defense peptides present in skin secretions and/or skin extracts of species belonging to other vertebrate classes (Agnatha, Elasmobranchii, Teleostei, Reptilia, and Mammalia as represented by the human) that supplement their potential role as anti-infectives for use against multidrug-resistant microorganisms.     

A phylogenetic analysis of species in the Bufo crucifer group (Anura: Bufonidae), based on indolealkylamines and proteins from skin secretions

This research tested the utility of two classes of skin secretion compounds to the phylogeny of the Bufo crucifer group. Skin secretions from specimens of nine populations of B. crucifer group were obtained and submitted to qualitative analysis. We observed a clear difference in the composition of the skin secretion molecules obtained from the species of Bufo studied. Fifty-nine molecules, 16 indolealkylamines and 43 proteins, were used as characters, and 39 of these were parsimonious informative. The tree topology of the skin secretion combined data showed areas of congruence and conflict when compared to an mtDNA phylogeny of the B. crucifer group. We used the Templeton test to evaluate the heterogeneity between the skin secretion and mtDNA data. Although not recommended, we performed a combined analysis with the two partitions. The skin secretion characters from the species of Bufo studied have phylogenetic signal. These data are indicative, at least as a preliminary study, of the phylogenetic relationships among the B. crucifer group taxa.     

Histological and mechanical evaluation of antifreeze peptide (Afp1m) cryopreserved skin grafts post transplantation in a rat model

The objective of this study was to evaluate the use of Afp1m as a cryopreservative agent for skin by examining the transplanted skin histological architecture and mechanical properties following subzero cryopreservation. Thirty four (34) rats with an average weight of 208 ± 31 g (mean ± SD), were used. Twenty four (n = 24) rats were equally divided into four groups: (i) immediate non-cryopreserved skin autografts (onto same site), (ii) immediate non-cryopreserved skin autografts (onto different sites), (iii) skin autografts cryopreserved with glycerol for 72 h and (iv) skin autografts cryopreserved with Afp1m for 72 h at −4 °C. Rounded shaped full-thickness 1.5–2.5 cm in diameter skin was excised from backs of rats for the autograft transplantation. Non-cryopreserved or cryopreserved auto skin graft were positioned onto the wound defects and stitched. Non-transplanted cryopreserved and non-cryopreserved skin strips from other ten rats (n = 10) were allowed for comparative biomechanical test. All skin grafts were subjected to histological and mechanical examinations at the end of day 21. Histological results revealed that tissue architecture especially the epidermal integrity and dermal-epidermal junction of the Afp1m cryopreserved skin grafts exhibited better histological appearance, good preservation of tissue architecture and structural integrity than glycerolized skin. However, there was no significant difference among these groups in other histological criteria. There were no significant differences among the 4 groups in skin graft mechanical properties namely maximum load. In conclusion, Afp1m were found to be able to preserve the microstructure as well as the viability and function of the skin destined for skin transplantation when was kept at −4 °C for 72 h.     

Angiotensinogen promoter and angiotensinogen II receptor type 1 gene polymorphisms and incidence of ischemic stroke and neurologic phenotype in Fabry disease

Abstract

Context: Stroke and/or white matter lesions (WMLs) are significant in Fabry disease. Polymorphisms of angiotensinogen (AGT), AGT Promoter and angiotensinogen II receptor type 1 (AGTR1) are correlated with WMLs.

Objectives: We compared AGT. AGT Promoter and AGTR1 genotypes to stroke incidence, Fabry-specific [Mainz Severity Score Index (MSSI)] severity score, and neurologic sub-score (n-MSSI).

Methods: Sixty-three Fabry patients and 49 matched controls plus historic controls were genotyped. Institutional Review Board approval was received.

Results. C and/or CC alleles of AGT Promoter and AGTR1 were significantly correlated with stroke and n-MSSI.

Discussion/conclusion: Findings are suggestive of role of AGT Promoter and AGTR1 genotypes in Fabry phenotypes.     

Sodium-Dependent Proline Uptake in the Rat Hippocampal Formation: Association with Ipsilateral-Commissural Projections of CA3 Pyramidal

Na+-dependent uptake of L-[3H]proline was measured in a crude synaptosomal preparation from the entire rat hippocampal formation or from isolated hippocampal regions. Among hippocampal regions, Na+-dependent proline uptake was significantly greater in areas CA1 and CA2-CA3-CA4 than in the fascia dentata, whereas there was no marked regional difference in the distribution of Na+-dependent gamma-[14C]aminobutyric acid ([14C]GABA) uptake. A bilateral kainic acid lesion, which destroyed most of the CA3 hippocampal pyramidal cells, reduced Na+-dependent proline uptake by an average of 41% in area CA1 and 52% in area CA2-CA3-CA4, without affecting the Na+-dependent uptake of GABA. In the fascia dentata, neither proline nor GABA uptake was significantly altered. Kinetic studies suggested that hippocampal synaptosomes take up proline by both a high-affinity (KT = 6.7 microM) and a low-affinity (KT = 290 microM) Na+-dependent process, whereas L-[14C]glutamate is taken up predominantly by a high-affinity (KT = 6.1 microM) process. A bilateral kainic acid lesion reduced the Vmax of high-affinity proline uptake by an average of 72%, the Vmax of low-affinity proline uptake by 44%, and the Vmax of high affinity glutamate uptake by 43%, without significantly changing the affinity of the transport carriers for substrate. Ipsilateral-commissural projections of CA3 hippocampal pyramidal cells appear to possess nearly as great a capacity for taking up proline as for taking up glutamate, a probable transmitter of these pathways. Therefore proline may play an important role in transmission at synapses made by the CA3-derived Schaffer collateral, commissural, and ipsilateral associational fibers.     

Connective tissue influences on the expression of epithelial cell-surface antigens

Summary Adult mice were found to show regional variation in the epithelial expression of some molecules of the blood-group antigen series. To investigate connective tissue influences on such differences, heterotypic recombinants of epithelia and connective tissues from various regions were prepared and examined using monoclonal antibodies directed against bloodgroup antigens H and Le^y. The results indicate that epithelia may maintain a preexisting regionally specific pattern following recombination but that, in some recombinant matches, the connective tissue is capable of signalling redirection of the pattern of expression towards that typical of the epithelium with which it is normally associated.This work was supported by NIH-NIDR RO1-DEO-5190     

Immunofluorescent localization of collagen types I,III and IV,fibronectin, laminin,and basement membrane proteoglycan in developing mouse skin

Summary The distribution of various extracellular matrix components was studied in frozen sections of embryonic (14–18 days) and early postnatal (birth and 4 days post parturn) dorsal mouse skin using monospecific antibodies and indirect immunofluorescence. Basement membrane zone components — type IV collagen, laminin and heparan sulphate proteoglycan — were found to be uniformly and unchangingly distributed along the dermal-epidermal junction. In contrast, the distribution of interstitial matrix components — types I and III collagen, and fibronectin — was heterogeneous and varied with the stages of hair development. Collagens became sparse and were eventually completely removed from the prospective dermal papilla and from a one-cell-thick sheath of dermal cells around hair buds. They remained absent from the dermal papilla throughout hair organogenesis. Fibronectin was always present around dermal papilla cells and was particularly abundant along the dermal-epidermal junction of hair rudiments, as well as underneath hair buds. In contrast, in interfollicular skin, collagens accumulated in increasing density, while fibronectin became progressively sparser. It thus appears that interstitial collagens and fibronectin are distributed in a manner which is related to hair morphogenesis. In morphogenetically active regions, collagen density is low, while that of fibronectin is high. Conversely, in histologically stabilized zones, collagen is abundant and fibronectin is sparse. This microheterogeneous distribution of interstitial collagens and of fibronectin might thus constitute part of the morphogenetic message that the dermis is known to transmit to the epidermis during the development of skin and of cutaneous appendages.     

Effects of wearing two different types of clothing on body temperatures during and after exercise

The experiment was conducted to investigate the human thermoregulatory responses during rest, exercise and recovery atT _a 20°C and 60% R.H. under the conditions of wearing two different types of clothing. Six healthy men wore two types of clothing: one covering the whole body area except the head (Type A, weight 1656 g), and the other covering only the trunk, upper arms and thighs (Type B, weight 996 g). The level of rectal temperature was kept significantly higher in Type B than in Type A during rest and recovery. The increased and decreased rates of rectal temperature during exercise and recovery were significantly greater in Type A than in Type B, respectively. These findings are discussed from the viewpoint of the differences of skin temperatures of the extremities between Type A and Type B.     

Biological activities caused by far-infrared radiation

Contrary to previous presumption, accumulated evidence indicates that far-infrared rays are biologically active. A small ceramic disk that emist far-infrared rays (4–16 m) has commonly been applied to a local spot or a whole part of the body for exposure. Pioneering attempts to experimentally analyze an effect of acute and chronic radiation of far-infrared rays on living organisms have detected a growth-promoting effect in growing rats, a sleep-modulatory effect in freely behaving rats and an insomiac patient, and a blood circulation-enhancing effect in human skin. Question-paires to 542 users of far-infrared radiator disks embedded in bedelothes revealed that the majority of the users subjectively evaluated an improvement of their health. These effects on living organisms appear to be non-specifically triggered by an exposure to far-infrared rays, which eventually induce an increase in temperature of the body tissues or, more basically, an elevated motility of body fluids due to decrease in size of water clusters.     

Desipramine Binding: Relationship to Central and Sympathetic Noradrenergic Activity

We examined the effects of treatments affecting norepinephrine release on the number of norepinephrine reuptake recognition sites as reflected by desipramine binding. To do this, we used manipulations having similar presynaptic but contrasting postsynaptic effects. Presynaptic inhibition by 6-hydroxydopamine lesion or by clonidine, and postsynaptic receptor stimulation by isoproterenol, reduced desipramine binding. Presynaptic stimulation by d-amphetamine and postsynaptic receptor blockade by prazosin increased desipramine binding. Similar effects and binding properties were seen in cerebral cortex, heart, and soleus muscle. After unilateral noradrenergic lesions, reduction in desipramine binding correlated with reduction in norepinephrine uptake. These results show that norepinephrine reuptake appears to be regulated by transmitter release regardless of effects on postsynaptic transmission, and that this regulation is analogous in the central and sympathetic nervous systems.