Acute rapamycin rescues the hyperexcitable phenotype of accumbal medium spiny neurons in the valproic acid rat model of autism spectrum disorder.

We previously demonstrated that prenatal exposure to valproic acid (VPA), an environmental model of autism spectrum disorder (ASD), leads to a hyperexcitable phenotype associated with downregulation of inward-rectifying potassium currents in nucleus accumbens (NAc) medium spiny neurons (MSNs) of adolescent rats. Aberrant mTOR pathway function has been associated with autistic-like phenotypes in multiple animal models, including gestational exposure to VPA. The purpose of this work was to probe the involvement of the mTOR pathway in VPA-induced alterations of striatal excitability. Adolescent male Wistar rats prenatally exposed to VPA were treated acutely with the mTOR inhibitor rapamycin and used for behavioral tests, ex vivo brain slice electrophysiology, single-neuron morphometric analysis, synaptic protein quantification and gene expression analysis in the NAc. We report that postnatal rapamycin ameliorates the social deficit and reverts the abnormal excitability, but not the inward-rectifying potassium current defect, of accumbal MSNs. Synaptic transmission and neuronal morphology were largely unaffected by prenatal VPA exposure or postnatal rapamycin treatment. Transcriptome analysis revealed extensive deregulation of genes implied in neurodevelopmental disorders and ionic mechanisms exerted by prenatal VPA, which was partially reverted by postnatal rapamycin. The results of this work support the existence of antagonistic interaction between mTOR and VPA-induced pathways on social behavior, neurophysiological phenotype and gene expression profile, thus prompting further investigation of the mTOR pathway in the quest for specific therapeutic targets in ASD.

Moderate ethanol drinking is sufficient to alter Ventral Tegmental Area dopamine neurons activity via functional and structural remodeling of GABAergic transmission.

Earlier studies have shown a major involvement of Ventral Tegmental Area (VTA) dopamine (DA) neurons in mediating the rewarding effects of ethanol (EtOH). Much less is known on the role of this system in mediating the transition from moderate to excessive drinking and abuse. Here we sought to explore the hypothesis that early stage drinking in rodents, resembling recreational EtOH use in humans, is sufficient to dysregulate VTA DA transmission thus increasing the propensity to use over time. To this purpose, midbrain slice recordings in mice previously exposed to an escalating (3, 6 and 12%) 18-day voluntary EtOH drinking paradigm was used. By recording from DA and γ-aminobutyric acid (GABA) VTA neurons in midbrain slices, we found that moderate EtOH drinking leads to a significant suppression of the spontaneous activity of VTA DA neurons, while increasing their response to acute EtOH application. We also found that chronic EtOH leads to the enhancement of GABA input frequency onto a subset of DA neurons. Structurally, chronic EtOH induced a significant increase in the number of GABA axonal boutons contacting DA neurons, suggesting deep rewiring of the GABA network. This scenario is consistent with a downmodulation of the reward DA system induced by moderate EtOH drinking, a neurochemical state defined as "hypodopaminergic" and previously associated with advanced stages of drug use in humans. In this context, increased sensitivity of DA neurons towards acute EtOH may represent the neurophysiological correlate of increased unitary rewarding value, possibly driving progression to addiction.

The SRA protein UHRF1 promotes epigenetic crosstalks and is involved in prostate cancer progression.

Epigenetic silencing of tumour suppressor genes is an important mechanism involved in cell transformation and tumour progression. The Set and RING-finger-associated domain-containing protein UHRF1 might be an important link between different epigenetic pathways. Here, we report that UHRF1 is frequently overexpressed in human prostate tumours and has an important role in prostate cancer pathogenesis and progression. Analysis of human prostate cancer samples by microarrays and immunohistochemistry showed increased expression of UHRF1 in about half of the cases. Moreover, UHRF1 expression was associated with reduced overall survival after prostatectomy in patients with organ-confined prostate tumours (P < 0.0001). UHRF1 expression was negatively correlated with several tumour suppressor genes and positively with the histone methyltransferase (HMT) EZH2 both in prostate tumours and cell lines. UHRF1 knockdown reduced proliferation, clonogenic capability and anchorage-independent growth of prostate cancer cells. Depletion of UHRF1 resulted in reactivation of several tumour suppressor genes. Gene reactivation upon UHRF1 depletion was associated with changes in histone H3K9 methylation, acetylation and DNA methylation, and impaired binding of the H3K9 HMT Suv39H1 to the promoter of silenced genes. Co-immunoprecipitation experiments showed direct interaction between UHRF1 and Suv39H1. Our data support the notion that UHRF1, along with Suv39H1 and DNA methyltransferases, contributes to epigenetic gene silencing in prostate tumours. This could represent a parallel and convergent pathway to the H3K27 methylation catalyzed by EZH2 to synergistically promote inactivation of tumour suppressor genes. Deregulated expression of UHRF1 is involved in the prostate cancer pathogenesis and might represent a useful marker to distinguish indolent cancer from those at high risk of lethal progression.

Causas más frecuentes de incontinencia fecal en nuestro medio / Most frequent causes of fecal incontinence in our environment

The objective of this piece of work was to assess the most frequent causes of fecal incontinence in our environment. 204 patients undergoing fecal incontinence of various types of severity were evaluated and later referred to "motilidad digestiva" department of Gastroenterology floor of Hospital de Clinicas Jose de San Martin, in an eight year span of time, 58 male (28.43 per cent) and 146 female (71.56 per cent) of an average age of 56 years. Every patient underwent a serious anamnesis, a proctologic examination, anoscopy, a rectosigmoid study, an anorectal manometry, and, a preventive electromyography was performed to those patients with a possible neurologic damage. The most frequent cause of incontinence was idiopathic 37.7 per cent, followed by post surgery (19.6 per cent) and rectal prolapse (13.7 per cent), post menopause (11.2 per cent), post delivery (9.8 per cent), Neurogenic Incontinence (4.9 per cent) and Traumatic Incontinence (2.9 per cent). Doctor's performance may prevent some of the causes of incontinence.

Causas más frecuentes de incontinencia fecal en nuestro medio / Most frequent causes of fecal incontinence in our environment

The objective of this piece of work was to assess the most frequent causes of fecal incontinence in our environment. 204 patients undergoing fecal incontinence of various types of severity were evaluated and later referred to "motilidad digestiva" department of Gastroenterology floor of Hospital de Clinicas Jose de San Martin, in an eight year span of time, 58 male (28.43 per cent) and 146 female (71.56 per cent) of an average age of 56 years. Every patient underwent a serious anamnesis, a proctologic examination, anoscopy, a rectosigmoid study, an anorectal manometry, and, a preventive electromyography was performed to those patients with a possible neurologic damage. The most frequent cause of incontinence was idiopathic 37.7 per cent, followed by post surgery (19.6 per cent) and rectal prolapse (13.7 per cent), post menopause (11.2 per cent), post delivery (9.8 per cent), Neurogenic Incontinence (4.9 per cent) and Traumatic Incontinence (2.9 per cent). Doctors performance may prevent some of the causes of incontinence. (Au)

Potential and limitations of magnetic resonance imaging for real-time monitoring of interstitial laser phototherapy.

RATIONALE AND OBJECTIVES: Magnetic resonance (MR) imaging has been suggested as a method to monitor interstitial laser phototherapy (ILP) in deep tissues. Unfortunately, a reliable relation between temperature and MR parameters has not yet been demonstrated. In this study, we examined whether such a relation exists and whether MR imaging can measure absolute temperature or temperature changes. METHODS: We evaluated, in the range of 21 degrees C to 80 degrees C, the temperature dependence of the MR imaging signal and T1 in samples of liver, water, CuSO4, and oil. Spin-echo and fast low-angle shot (FLASH) sequences were used. RESULTS: The MR imaging signal of liver, CuSO4, and water continuously decreased when the temperature was increased from 21 degrees C to 80 degrees C. By contrast, the MR imaging signal of the oil increased with increasing temperature up to 40-50 degrees C and then decreased at higher temperatures. We observed a reliable linear relation only between T1 and temperature in a range' of 30-60 degrees C for oil and CuSO4. CONCLUSION: MR imaging has the potential to measure thermal variations with an uncertainty of approximately +/- 10 degrees C. However, the use of MR imaging to monitor the real-time thermal effect induced in biologic tissues during laser irradiation requires further investigation before it can be applied clinically.

[Reliability of clinical parameters in the diagnosis of pulmonary thromboembolism at an emergency department]. / Affidabilità dei parametri clinici nella diagnosi di tromboembolia polmonare in Pronto Soccorso.

BACKGROUND: Pulmonary thromboembolism (PTE) mortality rate is four times greater among non-diagnosed than among diagnosed and hence suitably treated patients. Diagnosis, however, may be difficult due to the aspecific and polymorphic clinical picture of the disease. OBJECTIVE: We made a comparison between two groups of patients with PTE. In the first group the diagnosis was immediately suspected, in the second group it was delayed. The aim of our work was to identify any clinical or laboratory feature which may be helpful (singularly or jointly considered) to immediately recognize PTE in the Emergency Department. MATERIALS AND METHODS: 62 patients with PTE were studied retrospectively in 5 consecutive years. They came to E.D. because of symptoms and signs of cardiorespiratory failure. Pulmonary embolism was demonstrated in 60 cases by high probability pulmonary scan; in 2 cases (who suddenly died after the first visit) by autopsy. They were divided in two groups according to the first provisional diagnosis made after the first visit: group A (n 33 = 53.2%) with assumed pulmonary embolism; group B (n 29 = 46.8%) with other diagnosis. History, clinical findings, ECG, chest X-ray, blood gas analysis and routine laboratory tests were then compared between group A and group B patients. RESULTS: No differences were observed between diagnosed and non-diagnosed patients, except for a significantly higher rate of clinically overt deep venous thrombosis in group A. Three main clinical pictures were detected among our patients: 1-circulatory collapse syndrome: n = 20 (32.3%), of whom 8 in group A and 12 in group B (p = n.s.); 2-pulmonary infarction syndrome: n = 12 (19.4%), of whom 5 in group A and 7 in group B (p = n.s.); 3-uncomplicated embolism syndrome: n = 30 (48.4%), of whom 20 in group A and 10 in group B (p = n.s.). CONCLUSIONS: In our study, history and signs of deep vein thrombosis were the only clues significantly more represented in early diagnosed cases. The possibility of thromboembolic accident should never be dismissed, even despite lack of a proven emboligenous cause in patients with unexplained chest pain or cardiorespiratory failure.

[Orbital cellulitis in pediatric age. Report of a case and review of the literature]. / Cellulite orbitaria in età pediatrica. Descrizione di un caso e rassegna della letteratura.

The authors report about 2-year-old female affected by orbital cellulitis. The most recent advances about physiopathology, diagnosis and therapy of orbital cellulitis are described.

Full-blown hypothyroidism associated with vitiligo and acropachy. Report of one case.

During the first two years after the onset of hypothyroidism, a patient with spontaneous primary myxedema developed thyroid acropachy. Fifteen years before the diagnosis of thyroid disease, he had patchy vitiligo of the face. There were high serum levels of antibodies against thyroglobulin (anti-Tg) and microsomal antigen (anti-M) were present, while the serum levels of antibodies against the second antigen of the colloid and the cell-surface antigen fell within the normal range. Moreover, antibodies to gastric parietal cells, adrenocortical cells or pancreatic islets in the serum were not present. Concerning the immuno-genetic pattern of our patient, his HLA system did not appear to confirm the well documented prevalence in whites with autoimmune disorders of an antigen specificity positive for the locus DR3.

[Surgical correction of the pectus excavatum and carinatum in the adult. Report of an unusual case of combination of the straight back and pectus excavatum]. / Considerazioni sulla correzione chirurgica del "pectus excavatum" e "carinatum" nell'adulto. Descrizione di un raro caso di associazione pectus excavatum e straight back

Surgical correction of pectus excavatum et carinatum in a series of adult patients is described. The relationship between deformity of the anterior chest wall and cardiac, respiratory and digestive disturbances is assessed. The indications for surgical management are explained. Reference is also made to the satisfactory morphological and respiratory function results observed on follow-up. An unusual cases of pectus excavatum associated with straight back is separately described. Here again, successful surgical management was achieved, coupled with disappearance of functional disturbances and improvement of the heart picture.