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.     

Educational level as a modulator of cognitive performance and neuropsychyatric features in Parkinson disease.

OBJECTIVES: To test a possible association between the educational level (EL), cognitive performance, and neuropsychiatric features in Parkinson disease (PD). BACKGROUND: An inverse association has been reported between EL and cognitive dysfunction in patients with senile dementia of Alzheimer type but it is yet unsettled whether education has a similar effect on cognition in PD. METHODS: Seventy-two PD patients (45 males, mean age 68.7+/-11.6 y) underwent a detailed neurologic examination, a battery of neuropsychologic tests, and questionnaires for the evaluation of psychosis, sleep disturbances, and depression. According to the number of educational years, patients were divided into 3 groups: low EL (0 to 8 y), (15 patients), intermediate EL (9 to 12 y) (28 patients), and high EL (>/=13 y) (29 patients). RESULTS: Patients with a higher EL had a better cognitive function and an association was found between the patients' EL and their scores in various neuropsychologic tests mainly those sensitive to frontal lobe dysfunction. Low education was associated with an increased risk for hallucinations and a trend for more depression, delusions, and sleep disturbances. CONCLUSIONS: The association between high educational attainment and the lower risk of cognitive dysfunction suggest that education might modulate cognitive performance in PD.     

Progressive myoclonic ataxia with intrathecal immune activation in six patients

In six patients with slowly progressive sporadic cerebellar ataxia and cortical multifocal action myoclonus, cerebrospinal fluid (CSF) IgG index was persistently very high (1.2–6.7) and numerous oligoclonal bands were detected. Progressive cognitive impairment and MRI cerebellar and cerebral atrophy were observed. No serum antibodies were found. Various degenerative, metabolic, inflammatory and systemic diseases were excluded. The cerebellum may be the main target of a degenerative or immune process and releases antigens that, enhancing a compartmentalised (auto)immune response, as suggested by the persistent intrathecal activation, could lead to further cerebellar damage. As the frequency of CSF oligoclonal banding in myoclonic ataxia is unknown, our patients’ disease might represent a hitherto unreported entity or a subset of progressive myoclonic ataxia.

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Sommario Descriviamo sei pazienti con atassia cerebellare sporadica e mioclono corticale d’azione multifocale, nel cui liquor i valori dell’indice IgG si mantenevano persistentemente elevati ed erano presenti numerose bande oligoclonali. I pazienti manifestavano un progressivo declino cognitivo e la RM mostrava atrofia cerebellare e cerebrale. In assenza di anticorpi identificabili non era possibile formulare una diagnosi di malattia nota. Suggeriamo che il cervelletto possa essere il principale bersaglio di un processo degenerativo o immuno-mediato e che gli antigeni liberati inducano la produzione di anticorpi che ulteriormente provocano danno cerebrale. Poiché non è nota la frequenza delle bande oligoclonali nel liquor di pazienti con atassia mioclonica, non sappiamo se la malattia qui descritta sia una entità nuova o un sottogruppo delle atassie miocloniche.

     

National audit of incontinence surgery in the United Kingdom.

The aim of the study was to describe the experience, current trends and management of incontinence surgery for urodynamic stress incontinence (USI) in the United Kingdom. The study was a postal questionnaire survey that was sent to a cohort of surgeons known to be performing continence surgery. The subjects addressed included the considered role of the surgeon, the total number and type of operations performed in the last year, urodynamics and physiotherapy prior to incontinence surgery, operative complications, postoperative advice and follow-up (lengths and methods). The response rate was 54%. Large variations were found in all areas. The survey provides evidence of the number of incontinence operations performed, potentially important trends and differences in the practice and management of incontinence in the United Kingdom. This survey may be helpful in making guidelines and standards for audit at regional, local and individual levels as well as recommendations for strategies to enhance professional expertise in urogynaecology in the United Kingdom.     

The R7 subfamily of RGS proteins assists tachyphylaxis and acute tolerance at mu-opioid receptors.

Members of the R7 subfamily of regulators of G-protein signaling (RGS) proteins (RGS6, RGS7, RGS9-2, and RGS11) are found in the mouse CNS. The expression of these proteins was effectively reduced in different neural structures by blocking their mRNA with antisense oligodeoxynucleotides (ODNs). This was achieved without noticeable changes in the binding characteristics of labeled beta-endorphin to opioid receptors. Knockdown of R7 proteins enhanced the potency of antinociception promoted by morphine and [D-Ala(2), N-MePhe(4), Gly-ol(5)]-enkephalin (DAMGO)-both agonists at mu-opioid receptors. The duration of morphine analgesia was greatly increased in RGS9-2 and in RGS11 knockdown mice. The impairment of R7 proteins brought about different changes in the analgesic activity of selective delta agonists. Knockdown of RGS11 reduced [D-Ala(2)]deltorphin II analgesic effects. Those of RGS6 and RGS9-2 proteins caused [D-Ala(2)]deltorphin II to produce a smoothened time-course curve-the peak effect blunted and analgesia extended during the declining phase. RGS9-2 impairment also promoted a similar pattern of change for [D-Pen(2,5)]-enkephalin (DPDPE). RGS7-deficient mice showed an increased response to both [D-Ala(2)]deltorphin II and DPDPE analgesic effects. A single intracerebroventricular (i.c.v.) ED(80) analgesic dose of morphine gave rise to acute tolerance in control mice, but did not promote tolerance in RGS6, RGS7, RGS9-2, or RGS11 knockdown animals. Thus, R7 proteins play a critical role in agonist tachyphylaxis and acute tolerance at mu-opioid receptors, and show differences in their modulation of delta-opioid receptors.