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Adhess for ctnms~akwtce: Prof. G. BudiNon, Dipartimento di Medicina Clinica e Sperimentele, Unita di Gastroenterologie, Universita degli Studi “Federico ll”, vie S. Pansini 5, 8013 1 Napoli, ltely. Fax: +39-081-7462751. E-mail: gabudill@unine. it The recent history of medicine has been characterized by an important change in the definition of peptic ulcer, a common pathology of the upper digestive tract. In 1983, the hypothesis that ulcer had a bacterial aetiopathogenesis aroused much scepticism: ulcer was believed to be caused by excess gastric acid, evidence to this was the effectiveness of antisecretory drugs such as cimetidine and ranitidine. In 1994, the National Institute of Health Conference supported the use of antibiotics for the treatment of ulcers, thus accepting the bacterial hypothesis and contradicting the medical orthodoxy of the time, even against the interests of pharmaceutical industries. According to Paul Thagard, a philosopher of science, the history of ulcer disproves that science is either related to pure logic or power ‘. He believes that this discipline is both a social and a logical process, where technology and instrumentation play a crucial role. Science proceeds through an adaptive reasoning vaguer than probabilistic deduction, because it accounts both for the positive links with the interpretation of empirical data, and for the negative links that disprove conflicting hypotheses, in agreement with consolidated beliefs of a given period and historical setting 2. According to Thagard, the bacterial hypothesis was eventually accepted because its coherence in explaining the aetiology of the disease exceeded the alternative hypothesis in the new network that emerged from the empirical data and knowledge of the 90’s. At present Helicobacter pylori has become the undisputed protagonist of gastric pathology, from ulcer, to gastritis, to cancer. The identification of its genome, its biology, the interactions between the bacterium and its host, and the immune response, have led to the incredible progress experienced in the last 5 years. The knowledge of functional dyspepsia is not expected to meet the same destiny as ulcer and the other gastric pathologies. The development of diagnostic criteria in the last 15 years has improved our understanding of functional gastrointestinal disorders through a better definition of their symptoms, following the guidelines emerging from the Rome I and Rome II Consensus Conferences 7. The difference between aerophagia, functional vomiting and functional dyspepsia whether ulcer-like, dysmotility-like or aspecific seems to be well consolidated. However, the usefulness of a distinction between organic and functional disorders is still debated4. What needs to be further defined is the network of pathogenic interpretation relating the symptoms to specific pathophysiological alterations. Abnormal motility, visceral hypersensitivity, mucosal inflammation, neuro-immunological and psychological interactions between the brain and the intestine all make up the network of possible pathogenic interrelations. The technological tools available have become extremely sophisticated, among which imaging techniques, such as nuclear magnetic resonance (NMR), positron emission tomography (PET), and electrogastrographic, manometric and barostat methodologies. These are aimed at identifying the possible relations between specific areas of the central nervous system and the gastroduodenal peripheral motor system. Nowadays, there is still no scientific hypothesis capable of putting together, with explicative coherence, all the clinical and instrumental data available. However, an infective aetiopathogenesis has been postulated also for motility disorders, accounting for some of the functional abnormalities as possible con

In order to disclose the source of ascitic fluid in liver cirrhosis, normal and cirrhotic rats were injected with fluorescein into the paracecal vein. The green fluorescence was then evaluated on the surface of the liver, the intestine and the peritoneum. Among healthy rats and in those with anascitic cirrhosis a very slight fluorescence was detected on the liver capsule whereas among rats with ascitic cirrhosis a distinct fluorescence was shown on the liver surface, the small intestine and the peritoneum. Therefore, the peritoneum is a source of ascitic fluid in cirrhosis of the rat.

Peptidase and arylamidase activities were assessed in purified brush borders from jejunum of rats with surgically created blind loops. The blind loop segment and the jejunum proximal and distal to the blind loop were studied. Comparable jejunal segments from control rats were also studied. The blind loop syndrome was documented by presence of macrocytic anemia. Enzyme activities were determined on purified brush borders. In rats with the blind loop syndromes enzymatic activities hydrolizing sucrose, L-Leucyl-beta-naphthylamide, L-lysyl-beta-naphthylamide, alpha-L-glutamyl-beta-naphthylamide, L-phenylalanyl-alanine and L-leucyl-glycine were significantly reduced as compared to controls (P less than 0.001). After a short course of antibiotic therapy enzymatic activities returned to normal. Our findings suggest a reversible intestinal mucosa damage in the rat with blind loop syndrome.

The pattern and concentration of free amino acids in the plasma and liver tissue of phenobarbital-treated rats was investigated. In phenobarbital-treated rats, there was a significant plasma increase of the total concentration of free amino acids. No significant change in liver free amino acid concentration was observed because of the contemporaneous and general increase in liver size which does not allow observation of any percentual variation in amino acid concentration.

In human liver it is clearly evident that the levels of histidase and urocanase activities are considerably lower than those encountered in mouse liver. Both in the mouse and in the man urocanase presents levels of activity much higher than histidase. The apparent Km of histidine for the mouse histidase was 2.71 · 10−4M, whereas the Km for the human histidase was 4.83 · 10−4M; the apparent Km value of urocanase was 2.18· 10−6M for man, and 3.19sd 10−3M for the mouse. In mouse hepatitis there is a decrease of both enzyme activities in the liver and at the same time their passage in blood is observed. In human viral hepatitis the levels of both enzymes in blood plasma increase in an inconstant manner and no relationship can be observed with the extent of the hepatocellular damage.

The effects of oral phenobarbital (PB) administration on MHV-3 viral hepatitis in the mouse were studied. PB was effective in increasing liver cytochrome P-450 level in infected animals at 72 h after virus inoculation, but did not affect the disease process of the liver viral infection as judged by changes in mortality rate, serum GOT, GPT and MDH levels and liver virus content.

Variations in glutamic dehydrogenase and isocitric dehydrogenase levels have been studied in mitochondria, soluble phase of cytoplasm and blood plasma in mouse hepatitis by MHV-3 virus. In an early stage of the disease a partial alteration of mitochondria was observed as shown by increased solubilization of isocitric dehydrogenase following freezing and thawing as well as aging of mitochondria. In later stages of the disease, mitochondrial enzymes were released from mitochondria into the soluble phase of cytoplasm and from this to the blood stream. The data indicate that the glutamic dehydrogenase is less easily released into the blood stream, as shown by its increase in the soluble phase of cytoplasm in advanced stages of liver cell lesion.

Sono state studiate le variazioni di alcuni enzimi microsomiali del fegato di topi trattati con fenobarbital in varie fasi della epatite da MHV-3. E stato osservato che anche in fasi di avanzata citonecrosi epatica il trattamento con fenobarbital determina netti incrementi del citocromo P-450, della NADPH ossidasi e della anilina idrossilasi microsomiali. Nelle stesse condizioni invece la glucosio-6-fosfatasi mostra un decremento sia nei topi controllo che negli infetti.

Background/Aims: The synthesis of pyridine nucleotides from nicotinamide requires adenosine triphosphate. In man when exogenous nicotinamide is poorly utilized in this synthesis, the excess follows a dissipative metabolic pathway and is excreted in urine as N-methylnicotinamide. In human cirrhosis N-methylnicotinamide serum levels are higher than normal, in basal condition and after nicotinamide oral load, The aim of this study was to verify N-methylnicotinamide production in relation to hepatic content of adenosine triphosphate during in vitro perfusion of rat liver, in normal conditions and after adenosine triphosphate depletion by metabolic stress. Methods: ''Stress'' was obtained by pre-washing with saline for 15 min before the perfusion with nutritive medium. Results: The adenosine triphosphate decrease in the stressed liver was 38% after pre-washing with saline and 80% at the end of nutritive perfusion, In control liver the corresponding decreases were 1% after pre-washing with nutritive medium and 65% at the end of perfusion with the same medium, The total nicotinamide adenine dinucleotide decreases were 44% and 56% in the stressed liver, and 19% and 52% in the control liver, The output levels of N-methylnicotinamide at 90 min of rat liver nutritive perfusion were 31.50+/-4.72 nmol/g for normal liver and 66.40+/-13.17 for stressed liver (p