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Results from molecular docking calculations and Grid mapping laid the foundations for a structure-based optimization approach to improve the biological properties of pyrazolo-pyrimidine derivatives in terms of inhibition of Abl enzymatic activity and antiproliferative properties toward human leukemia cells. Insertion of halogen substituents with various substitution patterns, suggested by simulations, led to a significant improvement of leukemia cell growth inhibition and to an increase up to 1 order of magnitude of the affinity toward Abl.

Heme oxygenase-I (HO-1) has emerged as one of the most protective enzymes and its pleiotropic activities have been demonstrated in a variety of human pathologies. Unpublished observations have shown that HO-1 is induced after the infusion of ozonated blood into the respective donors, and many other experimental observations have demonstrated the efficacy of oxidizing agents. It appeared worthwhile to evaluate whether we could better define the activity of potential inducers such as hydrogen peroxide and ozonated human plasma. Human vascular endothelial cells at confluence were challenged with different concentrations of these inducers and the simultaneous production of nitric oxide (NO); and HO-1 was measured by either measuring nitrite, or bilirubin formation, or/and the immune reactivity of the protein by Western blot using a rabbit antihuman HO-1 and Hsp-70. The results show that production of both NO and HO-1 is fairly dose dependent but is particularly elevated using human plasma after transient exposure to a medium ozone concentration. At this concentration, there is also induction of Hsp-70. The results clarify another positive effect achievable by the use of ozone therapy.

The Authors report two cases of ectopic gastric pancreas, one of them causing a massive upper gastrointestinal hemorrhage, representing an infrequent complication of the disease. A literature review on the subject was then performed, and the importance of a differential diagnosis of the ectopy versus gastric malignancies, with relevant prognostical and management implications was assessed.

Acute appendicitis is a very common disease in western countries, affecting the entire population with higher prevalence in younger people. The diagnosis of the disease is still basically performed through the clinical evaluation of the patient, while peripheral White Cell Count or imaging techniques such as ultrasonography are poorly helpful. Therefore, a great number of patients is operated without finding a severe involvement of the appendix at intraoperative observation. To evaluate the rate of false acute appendicitis and to correlate the histological involvement with the clinical behavior of the disease the Authors carried a prospective study during a period of 28 months on 124 patients with a diagnosis of acute appendicitis treated on emergency basis.

Primary choledocholithiasis represents a quite unusual sequela of biliary tract surgery. Primary stones originate in the common bile duct and are soft, smooth, with a yellowish or brown-reddish colour, reproducing the shape of the duct in which arise. The Authors report a review of the cases observed in the division of General and Vascular Surgery-Department of Surgery and Surgical Emergencies of the University of Perugia. From January 1988 to December 1993, 577 laparotomic biliary tract operations were performed, and in 8 cases a re-operation was needed. Among the latter, particularly interesting were 2 cases of primary choledocholithiasis occurred in two patients with bilio-digestive anastomosis previously performed, i.e. two side-to-side Roux-en-Y or Braun loop choledochojejunostomies, respectively. Therefore, primary lithiasis following a choledochojejunostomy occurred when the bilio-digestive anastomoses were performed with the indication of a curative re-operation on the biliary tract. On the contrary, most choledochojejunostomies are performed as a palliative procedure in patients presenting a low survival rate not allowing to develop a Sump Syndrome and a consequent choledocholithiasis, which are long-term complications.

From January 1989 to December 1992, in the Institute of Clinical Surgery of the University of Perugia, 102 patients were admitted for thoracic trauma. Two patients with an open thoracic trauma, both presenting multiple shot-wounds, underwent an explorative thoracotomy. One of them died on the operating-table from hemorrhage, while the other was saved by a wedge-resection. A 3rd explorative thoracotomy was successfully performed on a patient with internal thoracic trauma and severe hemothorax. Among the 100 patients with an internal thoracic trauma, mortality was 6%, but only one of the 6 deceased, had no lesions other than a fail chest. As a matter of fact 38 patients presented lesions in other parts of the body. Simple and complicated multiple costal fractures, found in 84 cases, were the most frequent lesions observed. Seventeen of the 38 patients with pneumothorax and/or pleural effusion had a chest tube applied. Three patients were operated for a diaphragmatic hernia with a positive outcome. Only 75 patients received medical treatment without surgery. Six of the patients with multiple costal fractures presented flail chest. One of them (mentioned above) died almost immediately after his admission and therefore received no more than the initial medical treatment. Four others, aged over 65, successfully underwent a costal osteosyntesis, while the 6th patient received medical therapy with a positive outcome. In the case of a critical flail chest with severe patho-physiological consequences, if the fractures are in technically favourable sites, the Authors believe it is better to immediately stabilize the thorax, since the operating trauma is minimum and in many cases the patient is already intubated and curarized.

Inferior caval vein invasion not infrequently complicates advanced neoplastic lesions. Primitive caval neoplasms (leiomyosarcomas) or other tumors such as renal carcinomas, pheochromocytoma, as well as liver, testis, and retroperitoneal tumors most likely cause caval invasion. In the past, caval invasion was a clear index of non operability, while today, a modern multidisciplinary approach allows to treat successfully even so advanced diseases. In the present report the Authors analyze the cases treated at the Dept. of Surgery of the University of Perugia, and review the most important international reports on this subject illustrating the new possibilities offered by IVC substitution with biological or artificial grafts.

The authors present their diagnostic approach to acute intestinal ischemia. They underline the need for early specific diagnosis because the therapeutic options vary widely in relation to different types of acute intestinal ischemia. Selective arteriography preceded by an aortogram is considered the diagnostic "gold standard". Although at present mesenteric ischemia is a serious, and often lethal, disease, an aggressive therapeutic approach can improve the outcome of this group of patients.

Colorectal cancer is the second most common malignancy of the adult population in the United States. It is exceeded only by lung cancer among males and breast cancer among females. Malignancies of the colon and rectum are responsible for approximately 12 per cent of all adult cancer deaths. These tumors appear as surgical urgency by intestinal obstruction for 15-20 per cent and by perforation for 3-8 per cent of all cases. It often occurs in elderly patients; in fact, urgent surgical operations are especially performed in patients older than seventy. The mortality rate for urgent surgical operation in elderly patients is about 32-54 per cent. This high mortality is even due to concurrent pathologies and particular locoregional and/or general alterations induced by tumor. The authors studied all patients older than 75 years affected by colorectal cancer and treated by choice or by urgency at Dept. of Surgery of the University of Perugia from January 1987 to February 1993 to individualize some clinical, anatomo-pathological and therapeutical significant characteristics about colorectal cancer in geriatric age.

A new immunomodifier, [omega-(hypoxanthin-9-yl) pentoxy-carbonyl-leucyl-methionine] (RM06), was synthesized and its effect was evaluated on the activity of Natural Killer (NK) cells. Results indicate that RM06 is able to boost the NK activity of normal mice as well as to augment the regeneration of NK activity of lethally irradiated mice transplanted with syngeneic bone marrow (BM). This later effect also correlated with a significant increase in anti-tumor activity as evaluated by the resistance to metastasis in mice injected with syngeneic melanoma cells. These data indicate that RM06 is able to modulate the NK cell activity as well as the antitumor resistance.

Definite proof has been found that S. mutans, and probably S. sobrinus and lactobacilli, are responsible for caries in man. The aciduria of S. mutans encourages the selection inside the plaque and is directly responsible for its cariogenicity. Other aciduric species, as S. sobrinus, cause caries on the smooth surface of the tooth, where the principal causes of the rampant caries reside. If during the eruption of the tooth the fissures become colonized in depth by S. mutans, the development of caries becomes a highly probable event. Instead, if the colonization of the tooth by S. mutans takes place after the fissure depth have been occupied by other microbic species not cariogenic, it is probable that the caries will not manifest or will appear in a less severe form. In conclusion, the knowledge already acquired on the ecology of S. mutans and the mechanism of cariogenesis clearly indicate that all factors that interfere with the colonization of the tooth by S. mutans can greatly reduce the incidence of caries in man.