Fragile X mental retardation protein (FMRP) and metabotropic glutamate receptor subtype 5 (mGlu5) control stress granule formation in astrocytes.

Fragile X syndrome (FXS) is a common form of intellectual disability and autism caused by the lack of Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein involved in RNA transport and protein synthesis. Upon cellular stress, global protein synthesis is blocked and mRNAs are recruited into stress granules (SGs), together with RNA-binding proteins including FMRP. Activation of group-I metabotropic glutamate (mGlu) receptors stimulates FMRP-mediated mRNA transport and protein synthesis, but their role in SGs formation is unexplored. To this aim, we pre-treated wild type (WT) and Fmr1 knockout (KO) cultured astrocytes with the group-I-mGlu receptor agonist (S)-3,5-Dihydroxyphenylglycine (DHPG) and exposed them to sodium arsenite (NaAsO2), a widely used inducer of SGs formation. In WT cultures the activation of group-I mGlu receptors reduced SGs formation and recruitment of FMRP into SGs, and also attenuated phosphorylation of eIF2α, a key event crucially involved in SGs formation and inhibition of protein synthesis. In contrast, Fmr1 KO astrocytes, which exhibited a lower number of SGs than WT astrocytes, did not respond to agonist stimulation. Interestingly, the mGlu5 receptor negative allosteric modulator (NAM) 2-methyl-6-(phenylethynyl)pyridine (MPEP) antagonized DHPG-mediated SGs reduction in WT and reversed SGs formation in Fmr1 KO cultures. Our findings reveal a novel function of mGlu5 receptor as modulator of SGs formation and open new perspectives for understanding cellular response to stress in FXS pathophysiology.

Role of fragile X messenger ribonucleoprotein 1 in the pathophysiology of brain disorders: a glia perspective.

Fragile X messenger ribonucleoprotein 1 (FMRP) is a widely expressed RNA binding protein involved in several steps of mRNA metabolism. Mutations in the FMR1 gene encoding FMRP are responsible for fragile X syndrome (FXS), a leading genetic cause of intellectual disability and autism spectrum disorder, and fragile X-associated tremor-ataxia syndrome (FXTAS), a neurodegenerative disorder in aging men. Although FMRP is mainly expressed in neurons, it is also present in glial cells and its deficiency or altered expression can affect functions of glial cells with implications for the pathophysiology of brain disorders. The present review focuses on recent advances on the role of glial subtypes, astrocytes, oligodendrocytes and microglia, in the pathophysiology of FXS and FXTAS, and describes how the absence or reduced expression of FMRP in these cells can impact on glial and neuronal functions. We will also briefly address the role of FMRP in radial glial cells and its effects on neural development, and gliomas and will speculate on the role of glial FMRP in other brain disorders.

Nuck canal cyst involving right femoral vein: management and therapy of a rare clinical case.

We present a very rare case of a 49-year old woman suffering from Nuck canal cyst reaching and compressing femoral vein. Nuck canal cyst is very uncommon event because the pouch accompanying the gubernaculum during intrauterine descent of ovaries usually obliterates, whereas when it persists a cystic cavity containing citrine fluid develops. A gravid 0 para 0 49 old woman was admitted to Catania University Surgery Department owing to suspected lymphatic tumor compressing right femoral vein and causing groin pain with ipsilateral leg partial stasis. Patient believed right venous stasis was due to fibromatous uterus. Ultrasounds and computed tomography (CT) scan defined size (7.1 × 4.2 × 1.5 cm), structure (cystic) of mass and its relation with femoral vein, although they were not diriment for diagnosing its nature. Color Doppler detected circulatory function of compressed femoral vein. Surgery was challenging and Nuck cyst was removed after accurate separation from the right femoral venous walls. A case of Nuck cyst involving femoral vein has never been reported so far.

Endothelin-1 Induces Degeneration of Cultured Motor Neurons Through a Mechanism Mediated by Nitric Oxide and PI3K/Akt Pathway.

Endothelin-1 (ET-1) is a vasoactive peptide produced by activated astrocytes and microglia and is implicated in initiating and sustaining reactive gliosis in neurodegenerative diseases. We have previously suggested that ET-1 can play a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). Indeed, we reported that this peptide is abundantly expressed in reactive astrocytes in the spinal cord of SOD1-G93A mice and ALS patients and exerts a toxic effect on motor neurons (MNs) in an in vitro model of mixed spinal cord cultures enriched with reactive astrocytes. Here, we explored the possible mechanisms underlying the toxic effect of ET-1 on cultured MNs. We show that ET-1 toxicity is not directly caused by oxidative stress or activation of cyclooxygenase-2 but requires the synthesis of nitric oxide and is mediated by a reduced activation of the phosphoinositide 3-kinase pathway. Furthermore, we observed that ET-1 is also toxic for microglia, although its effect on MNs is independent of the presence of this type of glial cells. Our study confirms that ET-1 may contribute to MN death and corroborates the view that the modulation of ET-1 signaling might be a therapeutic strategy to slow down MN degeneration in ALS.

Pathological evaluation in colorectal polyps endoscopic treatment.

This retrospective study shows that endoscopic polypectomy is the technique of choice to remove the majority of polyps; follow-up and pathologic examinations shed light on the carcinogenesis of colorectal lesions. From January 1990 to December 2001, 1302 adenomatous polyps were removed, 1175 endoscopically, 127 with surgical procedures. The anatomical and morphologic conditions of the colon and some characteristics of the polyps represent limits to the feasibility and to the efficacy of polypectomy, and the most important variables for the correct management of the patients affected by colorectal adenomatous polyps.

Fragile X mental retardation protein (FMRP) interacting proteins exhibit different expression patterns during development.

Fragile X syndrome is caused by the lack of expression of fragile X mental retardation protein (FMRP), an RNA-binding protein involved in mRNA transport and translation. FMRP is a component of mRNA ribonucleoprotein complexes and it can interact with a range of proteins either directly or indirectly, as demonstrated by two-hybrid selection and co-immunoprecipitation, respectively. Most of FMRP-interacting proteins are RNA-binding proteins such as FXR1P, FXR2P and 82-FIP. Interestingly, FMRP can also interact directly with the cytoplasmic proteins CYFIP1 and CYFIP2, which do not bind RNA and link FMRP to the RhoGTPase pathway. The interaction with these different proteins may modulate the functions of FMRP by influencing its affinity to RNA and by affecting the FMRP ability of cytoskeleton remodeling through Rho/Rac GTPases. To better define the relationship of FMRP with its interacting proteins during brain development, we have analyzed the expression pattern of FMRP and its interacting proteins in the cortex, striatum, hippocampus and cerebellum at different ages in wild type (WT) mice. FMRP and FXR2P were strongly expressed during the first week and gradually decreased thereafter, more rapidly in the cerebellum than in the cortex. FXR1P was also expressed early and showed a reduction at later stages of development with a similar developmental pattern in these two regions. CYFIP1 was expressed at all ages and peaked in the third post-natal week. In contrast, CYFIP2 and 82-FIP (only in forebrain regions) were moderately expressed at P3 and gradually increased after P7. In general, the expression pattern of each protein was similar in the regions examined, except for 82-FIP, which exhibited a strong expression at P3 and low levels at later developmental stages in the cerebellum. Our data indicate that FMRP and its interacting proteins have distinct developmental patterns of expression and suggest that FMRP may be preferentially associated to certain proteins in early and late developmental periods. In particular, the RNA-binding and cytoskeleton remodeling functions of FMRP may be differently modulated during development.

[Recurrence after hernioplasty according to Lichtenstein: analysis of the cause]. / Le recidive dopo ernioplastica secondo Lichtenstein: analisi delle cause.

The performance of surgical interventions of tension-free hernia repair has certainly reduced the recurrence rate in comparison with the previous techniques; notwithstanding this it is not uncommon to observe some recurrences also after a Lichtenstein hernia repair. The aim of this study is that to analyse the causes. In the last 2 years, 42 patients (mean age of 68 years) with recurrent hernia have been operated by Lichtenstein technique; 11 of the 42 patients had been treated before with an useful mesh hernia repair. In 8 of these patients the recurrence was produced by an insufficient medial extension of the mesh; in the other 3 patients the cause was the presence of an unrecognized indirect hernia in patients operated for a direct inguinal hernia. All the patients treated have been submitted to a 18 months time of follow-up.

[Gastric lymphomas: surgical indications]. / I linfomi gastrici: indicazioni all'intervento chirurgico.

Primary gastric lymphoma (PGL) are lymphomas with an exclusive gastric localization. Histologically they are B-like non-Hodgkin lymphomas. Aim of Authors' study is to define the role of surgery in the treatment of PGL, on the basis of their series casistics and a review of the more recent literature data. The Authors observed 41 patients (23 F and 18 M) in a period of 10 years: 35 patients underwent to surgical operation associated in 18 of them to chemotherapic treatment; in 6 cases medical eradication of Helicobacter Pylori (H.P.) was performed as unique treatment. Antibiothic treatment allows the eradication of H.P. in 97% of the patients and a histologic decreasing of MALT lymphoma in 70% of the patients in about 6 months. That represents the first therapeutic choice for the low grade of malignancy MALT PGL at I and II stages. In the cases of partial decreasing or progression of PGL, the Authors consider opportune surgical operation. In the majority of the cases the surgical option represents, according to our advise, the best choice for the high percentage of definitive recoveries, allowing a 10 or more years of surviving of the 90%, if it is done in the first stages of the disease. The results of the association with neoadjuvant or aduvant chemotherapy are still controversial. On the basis of their experience total gastrectomy can be considered the elective choice operation, with IID level lymphadenectomy and possible splenectomy.

[Day-hospital treatment of inguinal hernia]. / Il trattamento delle ernie inguinali in regime di day-hospital.

Aim of the Authors' research was to evaluate advantages of day-surgery treatment for inguinal hernias. The study has been performed on a series of 138 patients, operated because of unrelapsed and uncomplicated monolateral inguinal hernia. Up-to-date therapeutic behaviour relating to hernia is the result of brilliant intuitions: technical order (tension-free repair), technological progresses (using new prosthetic materials), and refinement of anaesthesiological procedures (local and loco-regional anaesthesia). As regards surgical and anaesthesiological methods, general principles have been accepted by now from the most of the Authors. The new frontier of hernias' treatment is the possibility of operate in a day-hospital way: that means real advantages, both as regards patients' compliance and, in consideration of the high incidence of such pathology, as regards the high economic savings and more reasonable management of hospital stays. The significative increase of day-hospital hernioplastic operations in last years is due to standardization of restrictiveless criteria of choice for patients who can be treated with such modality.

[Varicose disease of lower limbs: our actual orientation]. / La malattia varicosa degli arti inferiori: nostro attuale orientamento.

A retrospective analysis of a series of patients treated during 5 years was made evaluating, on the basis of the clinical and ultrasonographic examination, the results obtained in the treatment of the varicose disease of the lower limbs for each one of three surgical methodic employed (crossectomy, long or short stripping) as well as patients compliance. All the patients previously underwent ultrasonographic examination to evaluate the reflux rank of the internal saphena and to point out every insufficient veins. On the basis of specific indications, from routinary pre-operative and anaesthesiologic examinations, all the patients were operated. Totally, 784 operations were performed. Thanks to the follow-up, carried out through an objective evaluation (echocolor-Doppler) and subjective one (degree of satisfaction fullfilled through some tests), it is concluded that the most favourable method, among those used, is that of short stripping with wrapping up a silk thread, in accordance to Van der Stricht.

[Retroperitoneal leiomyosarcoma: a case report]. / Il leiomiosarcoma del retroperitoneo: descrizione di un caso clinico.

The Authors report a rare case of retroperitoneal leiomyosarcoma in a 80 years woman with respiratory symptoms and right abdominal pain. A large neoplasm occupied the right abdomen, looking asymmetric. Upper abdominal CT showed a retroperitoneal neoplasm close to right kidney, liver, aponeurosis of right oblique muscles, producing a left-side dislocation of the intraabdominal organs. A surgical "en bloc" resection of the neoplasm was performed; neoplasm was plurilobed and capsulated. The histologic examination confirmed the diagnosis of leiomyosarcoma. The best treatment of these neoplasms is surgery, that in the last years has drawn advantage from more sensible and specific diagnostic procedures, which show a more radical surgical option. Though metastases are occasional, local recurrences can be taken into consideration and, after a careful tumoral re-staging, they can be resected once more. Therefore, a careful follow-up is necessary on the basis of neoplastic grading, extension and involvement of the closer structures.