The αvβ6 integrin plays a role in compromised epidermal wound healing

The alphavbeta6 integrin is an exclusively epithelial integrin that is highly expressed during fetal development. In adult tissue, alphavbeta6 integrin is expressed during inflammation, carcinogenesis, and in wound healing. We previously reported that alphavbeta6 integrin is highly expressed in poorly healing human wounds and its over-expression is associated with chronic wounds in a mouse model. The objective of this study was to investigate the role of alphavbeta6 integrin in compromised wound healing induced by hydrocortisone treatment or aging by using young and old mice deficient in or overexpressing the beta6 integrin subunit in the epidermis. Untreated aged beta6 integrin-deficient (beta6-/-) animals showed a significant delay in wound healing when compared to their age-matched controls or younger beta6-/- mice. The most significant delay was observed at the stages where granulation tissue deposition was occurring. Hydrocortisone treatment significantly delayed wound healing in wild-type and beta6 integrin-deficient mice in comparison with the untreated controls. However, hydrocortisone treatment in beta6 integrin overexpressing animals did not cause a significant delay in wound healing. The results of this study suggest that alphavbeta6 integrin plays an important role in wound healing in animals compromised by either age or stress mimicked by hydrocortisone.     

Does CA1 dopaminergic system play a role in cholestasis induced hypothermia?

ObjectiveThere is some of evidence describing that cholestasis induces hypothermia. Meanwhile, there is paucity of comprehensive data on the mechanism(s) governing this phenomenon. The present study was undertaken to determine the effect of CA1 dopaminergica system on cholestasis induced hypothermia.MethodsMale NMRI mice weighing 25–30 g, were used. Bilateral cannulae were implanted in dorsal hippocampi (CA1) for drug microinjection. Animals were randomly divided into non-operated control, sham-operated and bile duct-ligated (BDL) groups. Cholestasis was induced by means of main bile duct ligation. Body temperatures were measured before, two and four days after BDL.ResultsData indicated that, two and four days post BDL, the body temperature decreases as compared to the sham-operated animals, which indicates hypothermia. Intra-CA1 injection of different doses of sulpiride (SUL; 0.25, 0.5 and 0.75 μg/mouse), SCH23390 (SCH; 0.125, 025 and 0.5 μg/mouse), SKF38393 (SKF; 0.25, 0.5 and 1 μg/mouse) and quinpirole (QUI; 0.25, 05 and 0.75 μg/mouse) exerted no effect on body temperature in non-operated and sham operated mice, by themselves. Moreover, intra-CA1 injection of SUL, QUI or SKF blocked, whereas, SCH tended to increase BDL induced hypothermia.ConclusionsThe present data revealed that the CA1 dopaminergic system is possibly involved in the BDL induced impairment of thermoregulation.     

Protective effects of Scutellaria lindbergii root extract against oxidative-induced cell and DNA damage in mouse fibroblast-like cells

Context: Scutellaria lindbergii Rech. f. (Lamiaceae) is an Iranian species of Scutellaria which has been shown to exert antimicrobial, antioxidant and cytotoxic effects. Objective: The protective properties of total methanol extract (TME) of S. lindbergii and its fractions (defatted and CH₂Cl₂) were investigated against cytotoxic and genotoxic effects of H₂O₂ in NIH 3T3 cell line as non-malignant cells. Materials and methods: The cells were incubated with different concentrations of S. lindbergii root extracts [TME (15–250?μg ml^?1), defatted fraction (15–500?μg ml^?1) and CH₂Cl₂ fraction (5–40?μg ml^?1)] and toxic concentration of H₂O₂ (200?µM) at 37?°C for 2?h concurrently and Cell viability was quantitated by MTT assay. The antigenotoxic effect of extracts was investigated using comet assay. The cells were incubated with extracts [TME (25–250?μg ml^?1), defatted fraction (25–500?μg ml^?1) and CH₂Cl₂ fraction (5–40?μg ml^?1)] and H₂O₂ (25?µM) at 4?°C for 20?min, then the comet assay was performed. DNA damage was expressed as percentage tail DNA. Results: Total methanol extract of S. lindbergii and its fractions had a significant inhibitory effect on DNA damage. The IC₅₀ values of TME, defatted fraction and CH₂Cl₂ fraction against DNA damage were determined as 48, 138 and 8?μg ml^?1, respectively. Conclusion: S. lindbergii extracts can prevent oxidative DNA damage, which is likely due to its flavonoids and phenolic compounds as antioxidant constituents.     

Parechovirus Genotype 3 Outbreak among Infants,New South Wales,Australia, 2013–2014

From October 2013 through February 2014, human parechovirus genotype 3 infection was identified in 183 infants in New South Wales, Australia. Of those infants, 57% were male and 95% required hospitalization. Common signs and symptoms were fever >38°C (86%), irritability (80%), tachycardia (68%), and rash (62%). Compared with affected infants in the Northern Hemisphere, infants in New South Wales were slightly older, both sexes were affected more equally, and rash occurred with considerably higher frequency. The New South Wales syndromic surveillance system, which uses near real-time emergency department and ambulance data, was useful for monitoring the outbreak. An alert distributed to clinicians reduced unnecessary hospitalization for patients with suspected sepsis.     

Absence of alphavbeta6 integrin is linked to initiation and progression of periodontal disease

Integrin alphavbeta6 is generally not expressed in adult epithelia but is induced in wound healing, cancer, and certain fibrotic disorders. Despite this generalized absence, we observed that alphavbeta6 integrin is constitutively expressed in the healthy junctional epithelium linking the gingiva to tooth enamel. Moreover, expression of alphavbeta6 integrin was down-regulated in human periodontal disease, a common medical condition causing tooth loss and also contributing to the development of cardiovascular diseases by increasing the total systemic inflammatory burden. Remarkably, integrin beta6 knockout mice developed classic signs of spontaneous, chronic periodontal disease with characteristic inflammation, epithelial down-growth, pocket formation, and bone loss around the teeth. Integrin alphavbeta6 acts as a major activator of transforming growth factor-beta1 (TGF-beta1), a key anti-inflammatory regulator in the immune system. Co-expression of TGF-beta1 and alphavbeta6 integrin was observed in the healthy junctional epithelium. Moreover, an antibody that blocks alphavbeta6 integrin-mediated activation of TGF-beta1 initiated inflammatory periodontal disease in a rat model of gingival inflammation. Thus, alphavbeta6 integrin is constitutively expressed in the epithelium sealing the gingiva to the tooth and plays a central role in protection against inflammatory periodontal disease through activation of TGF-beta1.     

GABA(A) receptors of hippocampal CA1 regions are involved in the acquisition and expression of morphine-induced place preference.

In the present study, the effects of bilateral intra-hippocampal CA1 (intra-CA1) injections of GABA(A) receptor agonist and/or antagonist on the acquisition and expression of morphine-induced place preference in male Wistar rats have been investigated. The conditioning treatments with subcutaneous (s.c.) injections of different doses of morphine (0.5-7.5 mg/kg) induced a conditioned place preference (CPP) for the drug-associated place in a dose-dependent manner. Intra-CA1 administration of the GABA(A) receptor agonist, muscimol (0.25, 0.5 and 1 microg/rat) significantly inhibited the morphine (5 mg/kg, s.c.)-induced CPP. Intra-CA1 injections of different doses of the GABA(A) receptor antagonist, bicuculline (0.25, 0.5 and 1 microg/rat), in combination with an ineffective dose of morphine (0.5 mg/kg, s.c.) elicited a significant CPP. However, muscimol or bicuculline by themselves did not elicit any effect on place conditioning. Furthermore, the muscimol-induced inhibition of morphine response was reversed by bicuculline (1 microg/rat, intra-CA1) administration. On the other hand, the bilateral intra-CA1 injections of muscimol (0.25, 0.5 and 1 microg/rat) or bicuculline (0.5, 1 and 2 microg/rat) significantly decreased the expression of morphine-induced CPP. Intra-CA1 administration of different doses of muscimol or bicuculline had no effect on locomotor activity in the testing phase. Our data indicated that the GABA(A) receptors of the hippocampal CA1 regions may play an important role in the acquisition and expression of morphine-induced place preference.     

Morphine state-dependent learning: sensitization and interactions with dopamine receptors

In the present study, the effects of morphine sensitization on impairment of memory formation and the state-dependent learning by morphine have been investigated in mice. Pretraining administration of morphine (0.5, 2.5 and 5 mg/kg) dose dependently decreased the learning of a one-trial passive avoidance task. Pretest administration of morphine (0.5, 2.5 and 5 mg/kg) induced state-dependent retrieval of the memory acquired under pretraining morphine influence. Pretraining or pretest administration of naloxone (0.25, 0.5 and 1 mg/kg) reversed both responses to morphine (5 mg/kg). Amnesia induced by pretraining morphine was significantly reversed in morphine-sensitized mice which had previously received once daily injections of morphine [20 and 30 mg/kg, subcutaneously (s.c.)] for 3 days. Morphine sensitization tended to reverse but did not significantly affect morphine state-dependent memory. The inhibition of morphine-induced amnesia in morphine-sensitized mice was decreased by once daily administration of naloxone (0.5, 1 and 2 mg/kg) 30 min prior to injection of morphine (20 mg/kg/day x 3 days). Three-days administration of 1-phenyl-7,8-dihydroxy-2,3,4,5-tetrahydro-1H-3-benzazepine HCL (SKF 38393; 8, 16 and 32 mg/kg) or SCH 23390; R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine HCL (0.01, 0.05 and 0.1 mg/kg) before morphine (for 3 days) and during morphine-sensitization, decreased and increased, the amnesia induced by pretraining morphine, respectively. Similar administration of quinpirole (0.5, 1 and 2 mg/kg) or sulpiride (25, 50 and 100 mg/kg) before morphine also decreased and increased the amnesia induced by pretraining morphine, respectively. The results suggest that morphine sensitization affects the impairment of memory formation, but not the facilitation of retrieval induced by morphine and thus it is postulated that dopamine receptors may play an important role in this effect.     

Localization of small leucine‐rich proteoglycans and transforming growth factor‐β in human oral mucosal wound healing

Wound healing in oral mucosa is fast and results in little scar formation as compared with skin. The biological mechanisms underlying this property are poorly understood but may provide valuable information about the factors that promote wound regeneration. Small leucine‐rich proteoglycans (SLRPs) decorin, biglycan, fibromodulin and lumican are extracellular matrix molecules that regulate collagen fibrillogenesis, inhibit transforming growth factor‐β (TGF‐β) activity and reduce scarring. In the present study, we analyzed accumulation of SLRPs and TGF‐β during non‐scarring human oral mucosal wound healing. Biopsies were collected from healthy volunteers from unwounded tissue and from standardized experimental wounds 3–60 days postwounding. Localization of SLRPs, TGF‐β1 and TGF‐β3 was analyzed by immunohistochemical staining and quantitated by image analysis. Double immunostaining was used to study localization of SLRPs or active TGF‐β in distinct cells. Decorin, biglycan, fibromodulin, and TGF‐β isoforms showed significantly increased accumulation in the wound extracellular matrix and distinct wound cells while the abundance of lumican in the extracellular matrix was strongly reduced during wound healing. Localization and abundance of fibromodulin, lumican, and TGF‐β isoforms was also spatiotemporally regulated in the wound epithelium. The findings suggest that SLRPs regulate wound reepithelialization and connective tissue regeneration during oral mucosal wound healing.