Environmental training is beneficial to clinical symptoms and cortical presynaptic defects in mice suffering from experimental autoimmune encephalomyelitis.

The effect of "prophylactic" environmental stimulation on clinical symptoms and presynaptic defects in mice suffering from the experimental autoimmune encephalomyelitis (EAE) at the acute stage of disease (21 ±â€¯1 days post immunization, d.p.i.) was investigated. In EAE mice raised in an enriched environment (EE), the clinical score was reduced when compared to EAE mice raised in standard environment (SE).Concomitantly, gain of weight and increased spontaneous motor activity and curiosity were observed, suggesting increased well-being in mice. Impaired glutamate exocytosis and cyclic adenosine monophosphate (cAMP) production in cortical terminals of SE-EAE mice were evident at 21 ±â€¯1 d.p.i.. Differently, the 12 mM KCl-evoked glutamate exocytosis from cortical synaptosomes of EE-EAE mice was comparable to that observed in SE and EE-control mice, but significantly higher than that in SE-EAE mice. Similarly, the 12 mM KCl-evoked cAMP production in EE-EAE mice cortical synaptosomes recovered to the level observed in SE and EE-control mice. MUNC-18 and SNAP25 contents, but not Syntaxin-1a and Synaptotagmin 1 levels, were increased in cortical synaptosomes from EE-EAE mice when compared to SE-EAE mice. Circulating IL-1ß was increased in the spinal cord, but not in the cortex, of SE-EAE mice, and it did not recover in EE-EAE mice. Inflammatory infiltrates were reduced in the cortex but not in the spinal cord of EE-EAE mice. Demyelination was observed in the spinal cord; EE significantly diminished it. We conclude that "prophylactic" EE is beneficial to synaptic derangements and preserves glutamate transmission in the cortex of EAE mice. This article is part of the Special Issue entitled "Neurobiology of Environmental Enrichment".

The reduction in glutamate release is predictive of cognitive and emotional alterations that are corrected by the positive modulator of AMPA receptors S 47445 in perinatal stressed rats.

S 47445 is a positive modulator of glutamate AMPA-type receptors, possessing neurotrophic and enhancing synaptic plasticity effects as well as pro-cognitive and anti-stress properties. Here, the drug was assessed in the perinatal stress (PRS) rat model, known to have a high predictive validity with monoaminergic antidepressants. The effects of a chronic treatment (i.p.) with S 47445 were investigated on risk-taking, motivational and cognitive behavior. S 47445 (1 and 10 mg/kg) increased the exploration of the elevated-plus maze and light/dark box as well as the time spent grooming in the splash test, and improved social memory in PRS rats. Also, the effects of S 47445 were examined on the synaptic neurotransmission. The reduced depolarization-evoked glutamate release induced by PRS was corrected with S 47445 (10 mg/kg). Remarkably, the reduction in glutamate release induced by PRS and corrected by S 47445 chronic treatment was correlated with all the behavioral changes. S 47445 at 10 mg/kg also normalized the lower levels of synaptic vesicle-associated proteins in ventral hippocampus in PRS rats. Finally, S 47445 reversed the decrease of mGlu5 receptors, GR and OXTR induced by PRS. Collectively, in an animal model of stress-related disorders, S 47445 corrected the imbalance between excitatory and inhibitory neurotransmission by regulating glutamate-evoked release that is predictive of PRS behavioral alterations, and also normalized the reduction of trafficking of synaptic vesicles induced by PRS. These results support the interest of glutamatergic-based therapeutic strategies to alleviate stress-related disorders.

Oral glucose tolerance test unravels circulating miRNAs associated with insulin resistance in obese preschoolers.

BACKGROUND: Circulating microRNAs (miRNAs) may act as biomarkers of metabolic disturbances. OBJECTIVE: The aim of this study was to identify serum miRNAs signature of early insulin resistance in obese preschoolers. METHODS: Twelve obese children, aged 2-6 years, six insulin resistant (IR) and six controls were selected being age-matched, sex-matched and body mass index-matched. Profiling of 179 circulating miRNAs, known to be widely expressed in the bloodstream, was investigated by quantitative polymerase chain reaction at fasting and 120 min following a standard oral glucose tolerance test (OGTT). RESULTS: Twenty-one miRNAs were differentially regulated in IR obese preschoolers. miR-200c-3p, miR-190a and miR-95 were differently regulated both at fasting and 120 min after the OGTT. In controls, the fold changes of some miRNAs were correlated with Δglucose0-120 (miR-660, miR-26b-5p and miR-22-3p: p = 0.005 for all) and Δinsulin0-120 (miR-660 and miR-22-3p: p = 0.02 for both and miR-423-5p: p = 0.042). In IR patients, miR-1 fold changes were correlated with Δglucose0-120( r = -0.786; p = 0.036) and Δinsulin0-120( r = -0.821; p = 0.023). CONCLUSIONS: Our study identifies circulating miR-200c-3p, miR-190a and miR-95 as biomarkers of insulin resistance in obese preschoolers, being differentially regulated in IR patients both in fasting condition and after the OGTT. Expression of some circulating miRNAs seems reflecting glucose and insulin excursion following the OGTT differently in controls and IR obese preschoolers.

[Pediatric non-alcoholic fatty liver disease: recent advances and challenges]. / Steatosi epatica non alcolica nel bambino: progressi recenti e nuove prospettive.

Non-alcoholic fatty liver disease (NAFLD) encompasses a range of liver histology severity and outcomes in the absence of chronic alcohol use. The mildest form is simple steatosis in which triglycerides accumulate within hepatocytes. A more advanced form of NAFLD, non-alcoholic steatohepatitis (NASH), includes inflammation and liver cell injury, progressive to cryptogenic cirrhosis. Although prevalence in children is very difficult to establish, NAFLD is probably the most common cause of liver disease in preadolescent and adolescent groups. Over the last two decades the rise in the prevalence rates of overweight and obesity likely explains the NAFLD epidemic worldwide. NAFLD is strongly associated with abdominal obesity, type 2 diabetes, and dyslipidemia, and most patients have evidence of insulin resistance. Thus, NAFLD shares many features of the metabolic syndrome, a highly atherogenic condition, and its presence could signify a substantial cardiovascular risk. Accurate diagnosis and staging of NAFLD requires liver biopsy. The development of non-invasive surrogate markers and the advancement in imaging technology will aid in the screening of large populations at risk for NAFLD. While the optimal treatment has yet to be determined, lifestyle modification through diet and exercise should be attempted in children diagnosed with NAFLD. This review outlines current understanding, recent advances and challenges on pediatric NAFLD for both clinicians and researchers. Key words: Fatty liver.

[The ATLS Courses in Italy. Twelve years experience]. / I Corsi ATLS (Advanced Trauma Life Support) in Italia. Dodici anni di attività.

ATLS Courses were introduced in the USA in 1980 and have been taught in Italy since 1994. Through theoretical lessons and practical sessions, their scope is to provide proper training for doctors with every kind of speciality who work in Emergency Departments, in order to prepare them to rapidly and effectively intervene on a patient who has suffered a serious trauma. Universities, in fact, do not prepare doctors adequately on this topic, while the application of the ATLS method in the first hours after trauma can effectively improve the prognosis of the patient. This study collects the data of the Italian experience in ATLS training, which has been carried out under the aegis of the Italian Chapter of the American College of Surgeons. The ATLS Courses have become widespread throughout our Country, which today is the fourth in the world for number of courses held every year.

Absence of gene mutations in a case of concomitant presence of carcinoid of the ampulla of vater pheochromocytoma and Von Recklinghausen disease.

The rare association between Von Recklin-ghausen's disease (VRD) and tumours other than in central nervous system is well recognized. However, the concomitance of VRD, a carcinoid of the ampulla of Vater, and a pheochromocytoma has been described very rarely in literature. Furthermore, the possible role of the genes usually involved in multiple endocrine neoplasia (MEN) syndromes, in this association, is unclear. We report the case of a patient affected by VRD and extra-adrenal pheochromocytoma, operated on in the past for a carcinoid of the ampulla of Vater. To determine if genes involved in MEN syndromes might play a role in this particular triad, we investigated the presence of somatic or germline mutations in the RET proto-oncogene and menin gene by non isotopic polymerase chain reaction single stranded conformation polymorphism (PCR-SSCP) and heteroduplex gel electro-phoresis. The results demonstrated that no somatic or germline mutations in the MEN-1 and MEN-2 genes were involved in the pathogenesis of these tumours.

[The role of apoptosis in hepatic graft rejection]. / Il ruolo dell'apoptosi nel rigetto del trapianto epatico.

In 1965, Kerr described a type of death, apoptosis, with different characteristics from necrosis. Apoptosis has an important role in the development and cell homeostasis. Excessive or insufficient apoptosis contributes to the pathogenesis of pathology like ischemia, neurodegeneration, autoimmunity, viral infection, and tumor growth or regression. Apoptosis is subdivided into four sequential phases: order of death; death of cell; phagocytosis of apoptotic bodies and degradation of apoptotic bodies. Death programs converge on sequential activation of a proteases family, caspases. Some aspects of graft rejection can be interpreted as failure of apoptosis in host immunity cells; sometimes rejection involves induction of apoptosis. Apoptotic-type lesions were found in early vascular occlusions, one of the cause of graft failure. Then, an augmented apoptosis in hepatic graft biopsy can be used like a signal of early vascular occlusion. In hepatic transplantation, apoptosis is followed by a proteolytic cascade, which causes sequential activation of caspases. Synthetic inhibitor of caspases can be used, then, in the prevention and/or treatment of pathologies with implication of apoptosis due to ischemia-reperfusion. These inhibitors are not enough for prevention of hepatic lesions, even if caspases inhibitor can be a strategy for treatment of hepatic graft rejection.

[Hereditary non polyposis colorectal cancer (HNPCC). A clinical and genetic entity]. / Il cancro ereditario non poliposico del colon-retto (HNPCC). Un'entità clinica e genetica.

The first description of hereditary non polyposis colorectal cancer goes back to Warthin's study in 1895. In 1966 two families with autosomal dominant predisposition to colon and endometrial cancer were found. This condition was defined initially as familial neoplasm syndrome, then Lynch syndrome, and at last hereditary non polyposis colorectal cancer (HNPCC). HNPCC is classically subdivided into Lynch syndrome I (characterized by predisposition to colorectal cancer with early age of onset, to cancer of the proximal colon, and excess of synchronous and metachronous cancer), and Lynch syndrome II (characterized by similar colic phenotype with augmented risk of extracolonic neoplasm). If all clinical characteristics are present, it is possible to suspect HNPCC: however, diagnosis is difficult. Histological and genetic features of colon cancer confirm the diagnosis of HNPCC. Surgical therapy of colic neoplasm is total colectomy. A careful screening of HNPCC family members is one of the cardinal point in prevention. Follow-up of these surgical patients is the same as for sporadic neoplasms.

[Cancer immunotherapy. A future therapeutical choice?]. / Immunoterapia dei tumori. Una futura scelta terapeutica?

The idea that there might be an immune response to cancer has been around for many years. Immunotherapy has a long history, but is only rarely considered as the treatment of choice. Immunotherapy has encountered a number of intrinsic difficulties in cancer, such as the antigenic resemblance between the tumour and normal cells, the rapid kinetic proliferation of tumour cells and their reduced immunogenicity. There are various types of immunotherapy. Aspecific immunotherapy augments the body s immune response without targeting specific tumoral antigens. In adoptive immunotherapy, cells are administered with antitumoral reactivity to mediate neoplasm regression. Specific active immunotherapy is based on the principle that neoplasm cells contain immunogenic sites against which an antitumoral immune response can be induced in an attempt to stimulate the immune system to target specific tumoral antigens. Vaccines against cancer cells are based on a more precise identification of the tumoral antigen components. Passive immunotherapy was limited by the difficulty of obtaining high titering and specificity in early attempts using polyclonal antisera; monoclonal antibodies are currently used alone or in association with radioactive substances and cytotoxic agents. Enormous progress has been made this century in the use of immunotherapy for cancer treatment. It seems likely that the next century will see its increased afficacy, making it one of the possible therapeutic options.

[Treatment of pain in the oncologic patient]. / Il trattamento del dolore nel paziente oncologico.

Around 65-85% of cancer patients suffer from pain at advanced stages. Pain is often inadequately treated, although it can be controlled simply in the majority of cases. It is important to try and achieve a number of targets, including pain control at night, resting pain and pain during movement. Pain can be divided into somatic pain caused by the stimulation of traditional nociceptors, visceral pain and neuropathic pain caused by damaged nervous fibres. All three types may exist in the same patient. Drugs are the main method used to control oncological pain. The three main classes of drugs (FANS, opioid analgesics and adjuvant analgesics) are used individually or in combination. Given that the collateral effects of opioid analgesics may limit their value, they must be monitored to ensure careful treatment. The appropriate use of invasive treatment in patients with advanced disease who do not respond to oral therapy may alleviate cancer pain in 10-30% of cases. These adjuvant procedures are classified as blockades of autonomous nervous tissue, peripheral nerves and neuraxis. In conclusion, the ability to give an overall evaluation of a patient with pain, to ensure the component administration of analgesic drugs and to inform the patient and the family forms the basis of the treatment of pain in cancer.

[Hemolysis and multiple trauma. A clinical case report]. / Emolisi e politrauma. Descrizione di un caso clinico.

A patient is described who presented hemolysis after a chest and head trauma. We checked out every possible cause of anemia and our conclusion is that trauma itself was the cause of hemolysis. As an explanation, we suggest that red blood cells were broken in lung capillaries because of endothelial damage due to pulmonary injury.

Rupture of thoracic aorta resulting from blunt trauma.

BACKGROUND: Traumatic rupture of thoracic aorta caused by blunt trauma has been observed more frequently in recent years. The aim of this study was to evaluate the state of the art of diagnostic methods used to identify this injury and the surgical techniques used to repair it. METHODS: The study was performed in 29 patients undergoing surgery for traumatic rupture of thoracic aorta from November 1979 to July 1995. RESULTS: All patients presented multiple blunt traumatic injuries. The suspicion of traumatic aortic rupture always arose when evidence of an enlarged mediastinal shadow was found on the chest X-ray, subsequently confirmed in 27 cases using aortography. During the period 1993-1995 11 patients underwent CT scan before aortography, which resulted false negative in 3 cases (27.2%). The decision to perform surgery was based on well defined priorities: abdominal injuries took priority over the aortic injury, and in stable patients with intracerebral injuries, head CT scan and neurosurgery were performed first. Eight patients died (overall mortality was 27.5%). CONCLUSIONS: CT scan should not be used for the diagnosis of aortic traumatic rupture because it is a waste of time (all patients have to undergo aortography before surgery) and the false negative rate is too high.

[Treatment of esophageal reflux by insertion of Angelchik prosthesis: analysis of the follow-up in 26 patients]. / Trattamento del reflusso esofageo mediante posizionamento di protesi di Angelchik: analisi del follow-up in 26 pazienti.

The authors report a retrospective analysis of the immediate and long-term results of treatment of gastroesophageal reflux refractory to medical therapy using the insertion of Angelchik's prosthesis in a group of 26 patients operated at the Institute of Emergency Surgery of Turin University from January 1980 to December 1993. All patients underwent pre- and postoperative endoscopy and were then controlled using esophagogastric X-ray, esophagogastroscopy, esophageal manometry and pH-metry in the event of disorders of esophageal motility. Operative mortality was nil and no major surgical complications were reported. Postoperative endoscopy showed the resolution of esophagitis in 23 patients (88.4%); symptoms of slight esophagitis persisted in 2 cases, and moderate esophagitis in another. Eighteen patients were monitored over time with a minimum follow-up of more than 2 years: persistent dysphagia appeared in 3 cases (16.6%), and in one patient this led to the need for endoscopic dilatations. Two patients (11.1%) presented "gas bloat syndrome" which gradually improved. It was never necessary to remove the device. No cases were observed of erosion, migration or destruction of the prosthesis. Follow-up exceeded 10 years in 7 patients, at present asymptomatic. Angelchik's prosthesis proved to be efficacious, rapid and simple to insert, and characterised by a lower morbidity rate and shorter postoperative course. The incidence of postoperative dysphagia makes only it is use indicated only in patients with a high operative risk, obese subjects and in case of recidivation of reflux after fundoplication.

[Treatment of traumatic injuries of the spleen. Retrospective analysis of 164 cases]. / Trattamento delle lesioni traumatiche della milza. Analisi retrospettiva su 164 casi.

Increased awareness of the spleen's immunologic function and the risk of overwhelming post-splenectomy sepsis has aroused interest in methods of splenic preservation in patients with abdominal trauma. During an 8-year period, 164 patients with documented blunt splenic injuries were treated in accordance with an evolving therapeutic program. Definitive treatment included nonoperative management in 19 patients (group I, 11.6%), repair in 50 (group II, 30.5%) and splenectomy in 95 (group III, 57.9%). Mortality and morbidity were higher in group III (6.3% and 34.3% respectively) according to the Injury Severity Score (ISS 33.3 +/- 13). In group II one patient died from severe head injuries. Only one patient failed nonoperative management and required laparotomy with resultant splenectomy on hospital day 10. Observation without surgery has proved to be safe and effective in children (failure incidence less than 10%); success rates in adults would not parallel the experience reported in children because of differences in anatomy and mechanism of injury. Selective criteria, including hemodynamic stability after initial fluid challenge, normal level of consciousness, lack of peritoneal signs, transfusion requirements of less than 4 units of blood, CT demonstration of minor splenic lesion and exclusion of associated abdominal injuries requiring surgery, make eligible for nonoperative management 12 to 18% of adults with anticipated success in over 75%. Operative repair or partial splenectomy can be employed in many patients, both adults and children, with a 1% incidence of rebleeding necessitating reoperation.

[Lesions of the spleen caused by blunt trauma. Proposal of a classification based on CT and correlation with prognosis and treatment]. / Lesioni della milza da trauma chiuso. Proposta di una classificazione basata sulla TAC e correlazione con prognosi e trattamento.

The use of CT scan has had a profound influence on the evaluation and treatment of closed abdominal injuries, enabling a progressive reduction to be achieved in the total number of emergency laparotomies. The authors review CT performed over the past two years in adult hemodynamically stable patients with traumatic splenic lesions. In 19 cases it was possible to commence non-surgical treatment which was successful in 18/19 cases. A simple and precise scoring system was elaborated on the basis of data obtained from CT by evaluating 4 parameters: extent of free intraperitoneal effusion, concomitant lesions to other abdominal organs, severity and site of splenic lesion. This classification gives a high degree of prognostic accuracy and provides a useful guideline in the choice of the most appropriate treatment.

[A double-blind study of neostigmine versus placebo in paralytic ileus as a result of surgical interventions]. / Studio in doppia cecità tra neostigmina en versus placebo nell'ileo paralitico conseguente ad interventi chirurgici.

A fully randomized double-blind study, stratified according to diagnosis, was carried out in order to assess the effect of endonasal neostigmine in the treatment of post-laparotic paralytic ileus. A total of 40 patients (16 M, 24 F), aged between 22 and 76 years old, were admitted to the study; of these 20 were cholecystectomized and 20 had undergone emergency surgery. According to a special randomization list, 10 patients from each pathological group were treated with 6% neostigmine en (1 puff = 5.4 mg) and the other ten were treated with placebo. Both treatments were administered at a dose of 2 puffs, one per nostril, at the end of surgery and then repeated every 4 hours up to a maximum of 6 puffs/day. Treatment was continued for 4 days or until canalization of feces and gas was achieved. The mean daily dose of endonasal neostigmine found to be efficacious was 4 puffs/day, equivalent to 24.7 mg in cholecystectomized patients and 23.5 mg in patients undergoing emergency surgery. In over-all terms the canalization of gas and feces was observed in 74% of patients treated with neostigmine and in 45% of those receiving placebo and the difference was statistically significant.

[Artificial nutrition in the injured patient]. / La nutrizione artificiale nel paziente traumatizzato.

Current knowledge of physiopathology allows better understanding of the metabolic and immunological alterations that occur after trauma, thus allowing more adequate treatment. Nutritional support is recognized as an important therapeutic intervention to promote wound healing, reduce the risk of infection and improve survival. The patient with severe trauma needs nutritional support from the beginning of treatment. The early administration of enteral nutrition is an important factor in the reduction of gut bacterial translocation and thus of septic complications. In the early phase, the parenteral route is capable of providing a sufficient calorific and protein support, whilst awaiting the recovery of the enteral route.

[Indications for the surgical treatment of esophageal varices hemorrhage]. / Indicazioni al trattamento chirurgico dell'emorragia da varici esofagee.

The authors present their experience in the treatment of acute bleeding from oesophageal varices. From 1983 to 1991, 596 patients underwent sclerotherapy during diagnostic endoscopy; a stop to bleeding was achieved in 512 cases (86%). Twenty-seven surgical emergency decompressive shunts were performed, 14 total portal-systemic and 13 selective; operative mortality was 64% and 54% respectively. One patient was submitted to oesophageal-gastric devascularization. Hundred-sixty elective shunts were performed, 99 total portal-systemic and 61 selective; operative mortality was 8% and 11% respectively. Since 1990 3 patients received liver transplantation. The 5-year survival rate of patients submitted to selective shunts was 46%; the 5-year survival rate of nonalcoholic cirrhotics submitted to shunt SRD was 73%.

[Cholelithiasis. Ultrasonography and other diagnostic methods. Usefulness, indications, and limitations]. / La calcolosi colecistica. L'ecografia ed altri mezzi diagnostici. Utilità, indicazioni e limiti.

It is reported that 12.5% of the Italian population suffer from cholecystopathy. The Authors carried out a retrospective analysis of the cases observed over an 18-month period. It was found that ultrasonography was the most appropriate screening method to reveal cholecystic pathologies and diseases of the biliary tract since it is specific and sensitive and also enables adjacent organs to be examined (liver, kidneys, aorta, pancreas, spleen).