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.

[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.

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.

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.

A study of 3H-PK 11,195 binding to "peripheral-type" benzodiazepine receptors on human lymphocytes. Evidence of decreased binding in hepatic encephalopathy.

In an attempt to assess the involvement of the "peripheral-type" benzodiazepine receptors (pBDZR) in hepatic encephalopathy (HE), we examined the binding of the isoquinoline carboxamide derivative 3H-PK 11,195 to lymphocyte membranes from a group of patients with liver cirrhosis with or without clinical signs of HE and normal controls. Lymphocyte 3H-PK 11,195 binding is saturable, with high affinity and presents the pharmacological specificity corresponding to pBDZR. A significant 40% decrease in the number of 3H-PK 11,195 binding sites, without a concomitant change in the apparent affinity, is observed in the group with HE as compared to the controls, but not in that with liver diseases without HE. The decrease in binding capacity correlates significantly with the clinical grading of HE, but not with age, sex, aetiology of cirrhosis or presence of surgical shunt. In contrast to the reduction of pBDZR, 3H-N-methylscopolamine binding to lymphocyte muscarinic receptors is not affected in HE. These findings are consistent with a role for pBDZR in HE and may stimulate studies of endogenous modulators and pharmacological agents for these receptors in the disease.

Estrogen receptors in colorectal adenocarcinomas and in other large bowel diseases.

Seventy-two patients with tumor and ten with non-neoplastic colon disease were studied for the presence of estrogen receptors (ER) by three different methods. Only seven specimens (six primary adenocarcinomas and one recurrent cancer) had an ER concentration above 3 fm/mg of cytosolic protein, with no sex, age and tumor stage correlation. Our results suggest that the large bowel does not contain a cytosolic receptor for estradiol.

Imipenem-cilastatin in the treatment of hospital infections.

Imipenem was tested on 65 gram-negative bacterial strains consecutively isolated in patients affected by hospital infection and used as empiric therapy in 52 patients presenting a hospital infection suspected of gram-negative origin. More than 96% of the tested strains resulted sensitive to imipenem. This antibiotic showed a good clinical result in more than 80% of the cases when used as therapy. Therefore imipenem could be considered the drug of first choice in patients with a severe prognosis and a nosocomial infection suspected to be due to a gram-negative microorganism.

A modified technique of orthotopic transplant of the kidney in rabbits.

In this study kidneys were harvested from bred-for-research cats weighing 4 to 5 kg. General principles of donor bilateral nephrectomy en bloc with aorta, vena cava, renal vessels, and ureters were followed. After the harvest the grafts were placed in lactated Ringer slush. A cuff was prepared on the renal vein over a 10 French plastic tube. The aorta was divided and left in connection with the renal artery at each side. Twenty female checkered Flemish giant rabbits weighing 4.0-6.0 kg served as recipients. After premedication with 40 mg/kg of ketamine, anesthesia was maintained with repeated doses (every 10-15 min) of a 0.1-mL mixture of 5 parts ketamine and 1 part acepromazine diluted 50% in a normal saline. Arterial pressure, CVP, blood gases, and temperature were monitored. Through a limited midline incision a native left nephrectomy was performed. The venous anastomosis was performed with a cuff technique without clamping the vena cava (which causes severe hemodynamic instability); the anastomotic time was 2-3 min. The arterial anastomosis was performed with an end-to-side aorta-to-aorta anastomosis; the anastomotic time was 5 to 7 min. There were no episodes of venous or arterial thrombosis. The donor procedure took approximately 40 min, and the backtable preparation of the graft an additional 45 to 60 min. Preparation of the recipient for the anastomosis took 15 min and the anastomotic time (warm ischemia) was 13 +/- 5 min. In this model suitable for xenograft research the duration of the surgery in the recipient has been greatly reduced because of (1) the previous backtable preparation of the graft, and (2) the cuff technique used for venous anastomosis. The present anesthesia regimen and careful hemodynamic monitoring were also important in the success of this model.

[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).

[Frequency of in vitro sensitivity to netilmicin and ceftizoxime on selected highly resistant flora in surgical intensive therapy]. / Studio delle frequenze di sensibilità "in vitro" a netilmicina e ceftizoxima su una flora altamente resistente selezionata in terapia intensiva chirurgica.

The in vitro sensitivity of 132 gram positive and gram negative bacterial strains to Netilmycin and Ceftizoxime was assessed in order to update the statistics on the a priori efficacy of the antibacterial drugs. The flora studied were carefully selected as an extreme case of resistance to the standard antibiotics. Netilmycin was found to be effective against Staphylococci, Pseudomonas and Enterobacter, Ceftizoxime against Serratia, Acinetobacter, Proteus and Klebsiella. Both drugs were equally effective against E. coli and Citrobacter.

[Colorectal tumors and hormonal receptors. A critical review of the literature]. / Tumori del colon retto e recettori ormonali. Una revisione critica della letteratura.

The importance of sexual hormones in the development of cancers of the large bowel is strongly supported experimentally and epidemiologically. The clinical search for the presence of hormonal receptors in the cells of patients operated for tumours of the colon and rectum has been common since 1975. This investigation ought to have opened up new diagnostic and therapeutic prospects for these tumours which have given such a little curative satisfaction. The present review considered reported data. Unfortunately the emerging picture is irregular in cases and results. It is personally considered that these studies are not for the moment likely to produce important novelties for the treatment of tumours of the large bowel tract.

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.

[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.

[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.

[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.

[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.

[Pancreatic pseudocyst as a complication of duodenocephalopancreatectomy. Description of a case]. / Pseudocisti pancreatica come complicanza di duodenocefalopancreatectomia. Descrizione di un caso.

Pancreatitis with the formation of a large pseudocyst on the pancreatic stump is a relatively rare complication of duodenopancreatectomy. An observed case is reported with an examination of its clinical and diagnostic aspects.

[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.