The dynamic reduction of Cu(II) to Cu(I) and not Cu(I) availability is a sufficient trigger for low density lipoprotein oxidation.

Copper (II) is one of the most widely employed experimental models to induce in vitro low density lipoprotein (LDL) oxidation. It is generally assumed that Cu(I), generated from active reduction of Cu(II), is the real trigger for the peroxidation of polyunsaturated fatty acids in LDL. We have employed isolated human LDL challenged with Cu(II) and the Cu(I) chelator bathocuproine disulfonic acid (BC) to test the validity of this hypothesis. At lower Cu(II)/LDL molar ratios, BC completely inhibited copper-mediated LDL oxidation evaluated either as thiobarbituric acid reactive substances (TBARS) production or changes in apo B100 electrophoretic mobility. On the contrary, at higher Cu(II)/LDL molar ratios, BC did not prevent LDL oxidation but rather markedly stimulated both the generation of TBARS and the increase of apo B100 electronegativity. These oxidative modifications were completely prevented by the Cu(II) chelator EDTA. Furthermore, the BC-Cu(I) complex alone was neither redox active nor active inducer of TBARS generation. These findings indicate that, under these experimental conditions, [1] Cu(I) is not necessary to promote LDL oxidation, [2] the availability of Cu(II) is a prerequisite and [3] some of the reaction(s) involved in Cu(II) reduction may play an essential role in initiating LDL oxidation.

Protective effect of dehydroepiandrosterone against copper-induced lipid peroxidation in the rat.

This study investigates the effectiveness and multitargeted activity of dehydroepiandrosterone (DHEA) as antioxidant in vivo. A single dose of DHEA was given IP to male rats. Liver and brain microsomes, and plasma low density lipoprotein (LDL), were isolated from rats sacrificed 17 h later. Liver and brain microsomes were challenged with CuSO(4) and, as index of lipid peroxidation, the production of thiobarbituric acid reactive substances (TBARS) was measaured. Also, plasma low-density lipoprotein (LDL) were challenged with copper and the time course of lipid peroxidation was evaluated following the formation of conjugated dienes. The onset of TBARS generation induced by copper was marked delayed in both liver and brain microsomes from DHEA-treated animals. Also, the resistance of LDL to oxidation, expressed by the duration of the lag-phase of the kinetic curve, was significantly enhanced in DHEA-treated rats. Results indicate that in vivo DHEA supplementation makes subcellular fractions isolated from different tissues and plasma constituents (LDL) more resistant to lipid peroxidation triggered by copper. The antioxidant effect on plasma LDL might be of special relevance to the proposed antiatherogenic activity of DHEA. Moreover, multitargeted antioxidant activity of DHEA might protect tissues from oxygen radicals damage.

Different mechanisms are progressively recruited to promote Cu(II) reduction by isolated human low-density lipoprotein undergoing oxidation.

The kinetics of Cu(II) reduction and its relationship to the process of low density lipoprotein (LDL) oxidation were investigated in isolated human LDL incubated with CuSO4 by using the Cu(I) chelator and indicator dye bathocuproine disulfonate (BC). The inclusion of BC in the incubation medium containing isolated LDL and different concentrations of CuSO4 revealed a biphasic kinetics of Cu(II) reduction consisting of an early phase followed by a plateau phase and a subsequent extensive reduction phase. The amount of Cu(I) formed during the early phase, as well as the rate of its generation, were strictly dependent on both the level of Cu(II) available (saturation was observed at 20 and 50 microM CuSO4) and the concentration of alpha-tocopherol within native LDL particles. Artificial enrichment of LDL with different concentrations of alpha-tocopherol led to a parallel increase of both the amount of Cu(II) reduced and the rate of reduction. The late phase of Cu(II) reduction was strictly related to the availability of copper but was largely independent from alpha-tocopherol. Neither the amount of Cu(I) generated nor the rate of generation were saturated at concentrations of copper up to 100 microM. Comparable results were obtained by adding BC at different time-points to the LDL-copper mixture, in order to measure at the same time-points both the true rate of Cu(II) reduction and the generation of TBARS during the dynamic process of LDL oxidation. The rate of Cu(II) reduction was already high during the lag-phase of the LDL oxidation profile and progressively decreased as alpha-tocopherol concentration decreased. The subsequent increase in the rate of Cu(II) reduction paralleled the formation of TBARS during the extensive LDL oxidation phase. These results suggest that different mechanisms of Cu(II) reduction, namely alpha-tocopherol-dependent and independent (likely lipid peroxide-dependent), are progressively recruited during copper-promoted LDL oxidation.

Chronic clonidine treatment and its withdrawal: effects on blood pressure and catecholamine synthesizing enzymes in brain-stem nuclei.

We have studied the effects of withdrawal from chronic clonidine treatment in the adult male spontaneously hypertensive rat (SHR). SHR received clonidine, 0.1 mg X kg-1 X day-1 i.v. for 10 days. Clonidine was delivered via osmotic minipumps. After 7 days of treatment there was a 16.5 +/- 2.5 mm Hg fall in mean arterial pressure. This was accompanied by a decrease in the dopamine-beta-hydroxylase and phenylethanolamine-N-methyl transferase activities of the A1/C1 region. Withdrawal from clonidine was characterized by tachycardia and an increase in mean arterial pressure and heart rate lability. Phenylethanolamine-N-methyl transferase of the the dopamine-beta-hydroxylase activity remained diminished. The dopamine-beta-hydroxylase activity of the A2/C2 region was also diminished during withdrawal. We suggest that the blood pressure lowering effect of clonidine is accompanied by a decreased capacity to synthesize adrenaline in the A1/C1 region where adrenaline could mediate a pressor effect. Increased blood pressure lability during withdrawal is accompanied by a restoration of synthesis of adrenaline in the A1/C1 region. There is also a decrease in the capacity of synthesis of noradrenaline in the A2/C2 region where adrenaline may mediate a vasodepressor effect.

Total anorectal reconstruction supported by electrostimulation gracilis neosphincter.

PURPOSE: To review and to update the results of Total Anorectal Reconstruction with Electrostimulated Graciloplasty (ES-TAR) at the same time as or following abdominoperineal resection (APR). SETTING: A university hospital in Italy. METHODS: Retrospective study. POPULATION: A series of 98 consecutive anorectal cancer patients who had undergone ES-TAR (in 88 cases at the same time as APR; in 10 cases following APR), 61 of whom are still evaluable in respect of continence (median follow-up period 55 months). RESULTS: There was no mortality. Thirty-seven percent of patients had postoperative complications with no impact on survival or functional outcome. The 5-year survival rate in 50 patients was 61% and the 5-year estimated cumulative probability of survival in 81 patients was 65%. Local recurrence rate was 16%. Continence was achieved in 87% of patients with a chronically stimulated TAR, and in 69% of patients with short-term stimulation. CONCLUSION: ES-TAR is a safe and effective method for both curing anorectal cancer and restoring continence. It may be considered a reliable alternative to sphincter-saving procedures in lower rectal cancer patients.

Tyrosine hydroxylase activity in the locus coeruleus of conscious rats: differences with the anesthetized rats.

Microdialysis was used to estimate in vivo tyrosine hydroxylase (TH) activity in locus coeruleus (LC) of conscious rats. An aromatic amino acid decarboxylase inhibitor, difluoromethyl-DOPA (DFMD), was perfused through the dialysis probe and the DOPA accumulating in dialysates was measured. A 3 h perfusion of a 6 x 10(-4) mol/l DFMD solution was needed to obtain measurable levels of DOPA in LC dialysates: a linear increase in DOPA concentrations was first observed and, then, a steady state. DOPA disappeared completely after inhibition of TH by alpha-methyl-p-tyrosine, showing that it reflects TH activity. The DFMD perfusion needed in this study was six times higher in concentration and three times longer in duration than the one required in a previous study we performed in LC of anesthetized rats. Furthermore, TH activity was found lower than the one we previously reported. We conclude that these differences could be explained by the effects of halothane anesthesia on DFMD and DOPA degradation and/or on LC neurons TH activity itself.

Laparoscopic treatment of pancreatic insulinoma.

Laparoscopy and laparoscopic ultrasonography (LUS) have been proposed for the diagnosis and treatment of pancreatic insulinoma. We present for cases of pancreatic insulinoma approached by laparoscopy guided by LUS. In three cases, insulinomas were in the pancreatic body and in one case in the pancreatic head. All lesions were detected preoperatively by abdominal US and confirmed by computed tomography. Laparoscopy was performed under general anesthesia. LUS was performed using a 10-mm flexible probe. In two cases the adenoma was enucleated using scissors and electrocoagulation, major vessels were controlled using clips, and enucleation was completed using a 30-mm endo-GIA. In one case a laparoscopic distal pancreatectomy with spleen preservation was performed. In one case the adenoma was deep in the pancreatic head; minilaparotomy was performed and the adenoma enucleated. Patients were discharged in good health 5-7 days after surgery. The postoperative course was complicated in one case of enucleation by peripancreatic fluid collection that was treated percutaneously. Our experience confirms that accurate localization followed by excision of tumors via the laparoscopic approach constitute a significant advance in the management of insulinoma.

Eosinophilic gastroenteritis: possible role of sonography in diagnosis and follow-up.

Eosinophilic gastroenteritis (EGE) is a rare disease of unknown etiology. The clinical and radiological diagnoses have to be confirmed by histological examination of biopsy specimens. The authors now present a case of a 19-year-old man with recurrent epigastric pain and vomiting, whose sonographic features and eosinophilia suggested the diagnosis of EGE, which was subsequently confirmed by histology. Sonographic follow-up permitted an effective evaluation of the evolution of the disease under steroid therapy.

Laparoscopic treatment of appendico-cecal intussusception.

Laparoscopy is a therapeutic possibility in pediatric surgery. A case of appendiceal intussusception treated laparoscopically in a 27-month-old girl is presented. The postoperative course was normal.

Anti-ulcer drugs and hypergastrinism: utilization in surgery.

The peptic ulcer disease associated with hypergastrinemia is very often a challenging problem of diagnosis and therapy. In absolute surgical emergency (haemorrhagic and perforative complications), the utilization of the most recently discovered anti-ulcer drugs appears to be extremely helpful; the prevention of incumbent complications can be accomplished, in fact, during the post-operative treatment and the "free time" so obtained can be used for an adequate differential diagnosis (gastrinoma-induced Zollinger-Ellison syndrome: antrum retained, G cells of the antrum hyperplastic, apud-tumours with hypersecretion). The "anti-H2 and anti-muscarinic" drugs (often in association) give the surgeon the possibility of an accurate diagnosis and the choice of the best surgical procedure (tumorectomy, DCP, gastrectomy). Even in elective surgery the prevention with anti-H2 drugs permits greater "safety margins" and an optimal follow-up study. The results of the surgical experience in the General Surgical Clinic of Pisa (18 cases of Z.E.'s) confirm the validity of the associated anti-ulcer therapy.

[A 1st experience with radical surgery of cancer of the rectum. Critical analysis of the literature and case reports, with special reference to methods "of security" and to technical guidelines for reducing complications and mortality]. / Una prima esperienza di chirurgia radicale per cancro del retto. Analisi critica della letteratura e della casistica, con particolare riferimento alla metodologia "di sicurezza" e alla impostazione tecnica per ridurre complicanze e mortalità.

An analysis of the most recent approaches to oncological surgery of the rectum, with particular reference to methods combining the greatest radicality with the lowest incidence of early and late complications, is followed by the presentation of work carried out over a period of four years at a subsidiary university department. A series of 77 radical operations (50 anterior and 27 abdominoperineal resections) is examined in function of the pre-, intra-, and postoperative measures making up the treatment protocol. The results are in line with the currently growing preference for anterior resection, and underscore the effectiveness of excluding right colostomy as a protective measure in low colorectal anastomosis. An absence of p.o. mortality a low incidence of complications significant with regard to short and long survival, and the data obtained from a short follow-up show that the methods are sound and in line with the more extensive university series, as well as the data in the literature

[Arterio-venous popliteal fistula: a rare late complication of a civilian trauma. A clinical case and review of the literature]. / Fistola artero-venosa poplitea: rara complicanza tardiva di un trauma civile. Caso clinico e revisione della letteratura.

In spite of the relatively high frequency of popliteal injuries following war and civilian traumas, a late development of an arteriovenous fistula can be considered an uncommon complication. We report a case of a chronic arterio-venous popliteal fistula in a young boy, caused five years previously by a blunt trauma, while playing. The tardive onset of symptomatology and the conspicuous enlargement of the vein underline the unusuality of the case. A review of the literature and the technique for fistula repair, using adsorbable suture, are examined.

[Use of defibrotide in the treatment of acute superficial thrombophlebitis of the legs]. / Impiego del defibrotide nel trattamento delle tromboflebiti acute superficiali degli arti.

The efficacy of defibrotide in the treatment of acute thrombophlebitis of the legs has been investigated in 140 patients, randomized into two groups. All patients received defibrotide either alone or as an addition to conventional therapies. Two different schemes of administration were selected and carried out in each group, according to the time of onset of thrombophlebitis. Defibrotide demonstrated a good clinical efficacy in both groups, with a highly significant reduction in those patients receiving defibrotide and conventional therapies. The clinical result were outstanding in two subgroups: extensive thrombophlebitis and brachioaxillary phlebitis.

[The prevention of postoperative deep venous thrombosis with heparan sulfate per os. A controlled clinical study vs. heparin calcium]. / Prevenzione della trombosi venosa profonda postoperatoria con eparansolfato per os. Studio clinico controllato vs eparina calcica.

The paper reports the results of a randomised study carried out on a pool of 100 patients undergoing surgery in order to assess the efficacy and tolerability of orally administered heparan sulfate versus heparin calcium in the prevention of postoperative deep-vein thrombosis. Despite the limits of oral administration, heparan sulfate is indicated in the pharmacological prevention of postoperative deep-vein thrombosis.

Quality of life after total anorectal reconstruction: long-term results.

The aim of the study was to assess the long-term quality of life (minimum 8 years after surgery) of patients undergoing total anorectal reconstruction for low rectal cancer. The quality of life of 27 patients undergoing total anorectal reconstruction (mean age: 73.07 years) and 27 healthy subjects (mean age: 73.50 years) randomly chosen from the population was analysed and compared using general standardized questionnaires and specific fecal continence scales. Twenty-one out of 27 patients were clinically evaluated and personally interviewed by the same surgeon who had performed the reconstruction some years before. Quality of life analysis yielded good global results, also in the light of the mean age of the patients. Fecal continence was obtained in 81% of patients. All of them report a good physical, psychological and social situation. There was no statistically significant difference (P = ns) in quality of life between these 27 total anorectal reconstruction patients and the control population. In adequately selected patients, total anorectal reconstruction is proposed as a technique capable of guaranteeing good quality of life as well as being a safe technique for the treatment of low rectal cancer.

[Risk factors and etiopathogenesis of cancer of the gallbladder]. / Fattori di rischio ed eziopatogenesi del cancro della colecisti.

Primary cancer of the gallbladder is uncommon but not rare, being in Italy the fourth cause of death for gastrointestinal cancer in females over 65 years old. Two centuries after the first description, this tumor remains characterized by an unfavorable prognosis due to the silent progression of the clinical course and the frequent unresectability at the time of surgery. Early diagnosis, aggressive surgical approach and chemotherapy are the basis for longer post-operative survival rates; in fact, despite the advances in ultrasonography and computer-assisted imaging devices, the prevention of gallbladder cancer remains a problem. In the statistical terms, the risks of an indiscriminate surgical prophylaxis would outweigh the advantages of cancer prevention; in this optic, a recognition of the patients "at major risk" appears to be essential. With this aim we have undertaken a review of current knowledge of the "risk factors" involved in the epidemiology and etiology of gallbladder cancer, deduced from Literature and our surgical experience. It is reasonable to assume that the etiology of this cancer is based on the correlationship between factors with a wide and different penetration in racial-ethnic areas: genetic, systemic and local risk-factors. A genetic influence can be highly suspected in the familiar cases, in the non-carcinoma tumors and in the geographic predominance of the tumor. None of the systemic factors suggested as risk factors (age, sex, obesity, occupational and chemical carcinogens, drugs, etc.) appear to be directly involved; moreover, the main factors, such as female sex and age, are probably mediated through cholelithiasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical evaluation of hepatic lesions: guidelines for diagnostic protocols and injury severity scores.

The standardisation of diagnostic procedures according to an adequate sequence is a mandatory in determining the therapeutic strategy in liver traumas. In a series of 26 consecutive cases of trauma of the liver, 3 of them penetrating, we adopted a diagnostic algorithm based on the extensive use of sonography and "Injury Severity Scores" in addition to the standard clinical procedures. The treatment of the lesions was surgical in 21 cases (81%) and conservative in 5 (19%); post operative mortality was 14% and overall mortality 11.5%. None of the cases treated by conservative approach had to be submitted to surgery during the follow-up period. Sonography, carried out by surgical staff within 30' from observation and at definitive intervals, allowed a correct surgical approach in all cases; a similar sensitivity was obtained by sonography also in the cases treated conservatively and submitted to C.T. evaluation. The absolute correlation between Revised Trauma Score, Injury Severity Scale, classes of severity of the lesions and subsequent surgical survey suggest that this scoring system could be adopted in the first triage of traumatic lesions of the liver. Sonography could be preferred to diagnostic peritoneal lavage in the screening of cases with circulatory instability; furthermore, it could be a valid alternative to C.T. in hemodynamically stable patients.

Is elastography actually useful in the presurgical selection of thyroid nodules with indeterminate cytology?

BACKGROUND: Although fine-needle aspiration cytology remains the mainstay of the preoperative workup of thyroid nodules, those with follicular proliferation still represent a diagnostic challenge. Real-time elastography (RTE) estimates the stiffness/elasticity of lesions and is regarded as a promising technique for the presurgical selection of thyroid nodules (including those with indeterminate cytology). AIM: Our aim was to verify the potential role of RTE in the presurgical diagnosis of cancer in a large cohort of consecutive patients with follicular thyroid nodules. PATIENTS AND METHODS: One hundred two patients were submitted to conventional ultrasonography and RTE evaluation before being operated on for thyroid nodule with indeterminate cytology (54% single nodules). Tissue stiffness on RTE was scored from 1 (greatest elasticity) to 4 (no elasticity). RESULTS: At conventional ultrasonography examination, the nodules (median diameter 2.2 cm) were solid (cystic areas < 10%); microcalcifications were detected in 56% of them and a hypoechoic pattern in 64%. Elasticity was high in eight cases only (score 1-2) although low in 94 (score 3-4). Cancer was diagnosed in 36 nodules (35%), being associated with microcalcifications (P < 0.0001) and inversely related to nodule diameter (P < 0.01). Malignancy was detected in 50% of the nodules with RTE score 1-2 and in 34% of those with score 3-4. Therefore, either the positive (34%) or the negative predictive value (50%) was clinically negligible. CONCLUSIONS: The current study does not confirm the recently reported usefulness of RTE in presurgical selection of nodules with indeterminate cytology and suggest the need for quantitative analytical assessment of nodule stiffness to improve RTE efficacy.