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PubMed2004

Interferon plus ribavirin and interferon alone in preventing hepatocellular carcinoma: a prospective study on patients with HCV related cirrhosis.

AIM: To determine the role of interferon (IFN) with or without ribavirin in preventing or delaying hepatocellular carcinoma (HCC) development in patients with hepatitis C virus (HCV) related cirrhosis. Data on the preventive effect of IFN plus ribavirin treatment are lacking. METHODS: A total of 101 patients (62 males and 39 females, mean age 55.1+/-1.4 years) with histologically proven HCV related liver cirrhosis plus compatible biochemistry and ultrasonography were enrolled in the study. Biochemistry and ultrasonography were performed every 6 mo. Ultrasound guided liver biopsy was performed on all detected focal lesions. Follow-up lasted for 5 years. Cellular proliferation, evaluated by measuring Ag-NOR proteins in hepatocytes nuclei, was expressed as AgNOR-Proliferative index (AgNOR-PI) (cut-off = 2.5). Forty-one patients (27 males, 14 females) were only followed up after the end of an yearly treatment with IFN-alpha2b (old treatment control group = OTCG). Sixty naive patients were stratified according to sex and AgNOR-PI and then randomized in two groups: 30 were treated with IFN-alpha2b + ribavirin (treatment group = TG), the remaining were not treated (control group = CG). Nonresponders (NR) or relapsers in the TG received further IFN/ribavirin treatments after a 6 mo of withdrawal. RESULTS: AgNOR-PI was significantly lowered by IFN (P<0.001). HCC incidence was higher in patients with AgNOR-PI>2.5 (26% vs 3%, P<0.01). Two NR in the OTCG, none in the TG and 9 patients in the CG developed HCC during follow-up. The Kaplan-Mayer survival curves showed statistically significant differences both between OTCG and CG (P<0.004) and between TG and CG (P<0.003). CONCLUSION: IFN/ribavirin treatment associated with re-treatment courses of NR seems to produce the best results in terms of HCC prevention. AgNOR-PI is a useful marker of possible HCC development.

Antineoplastic Agents↗

PubMed1979

The role of the reactive disulfide bond in the interaction of cholera-toxin functional regions.

The chemical reactivity of disulfide bonds towards reducing agents, in the absence of denaturing conditions, in cholera toxin has been studied. Treatment of the toxin with dithiothreitol or other mercaptans gave selective reduction of one of the six disulfide bonds of the protein. This reactive disulfide links two distinct functional regions of the toxin, fragment alpha, which activates adenylate cyclase, and fragment gammabeta5, which recognizes the cell surface receptors. Upon reduction, the two fragments remain bound together and the secondary structure of the protein is retained. The two functional regions have been separated and purified only by methods based on charge differences. When mixed together, purified alpha and purified gammabeta5 fragments spontaneously and rapidly re-form the disulfide bond. However, reduction of the disulfide bond is an absolute requirement for freeing the catalytic site of the alpha functional region. Thus, while other non-covalent binding regions are involved in maintaining cholera toxin molecular structure, the reactive disulfide bond may play a role in the mechanism of cell intoxication.

Binding Sites↗

PubMed2004

[Retrospective study of patients who undergo pacemaker implantation in short-stay ambulatory surgery. Long-term follow-up and cost analysis].

INTRODUCTION AND OBJECTIVES: The aim of this study was to analyze data concerning mortality, morbidity, the number of re-admissions, complications, and cost per patient after pacemaker implantation, in groups of patients with different postoperative follow-up regimens. PATIENTS AND METHOD: Data from 2108 patients with definitive pacemakers implanted between January, 1991 and December, 2001 were analyzed retrospectively. We took into account the length of hospital stay and pacemaker dependence: group I, non-pacemaker dependent ambulatory patients with no hospital admission (NPMD) (n=710); group II, pacemaker-dependent patients with a short hospital stay of up to 48 hours (PMD) (n=779); group III, non-pacemaker-dependent patients with routine hospitalization for more than 48 hours (NPMD) (n=289); and group IV, pacemaker-dependent patients with routine hospitalization for more than 48 hours (PMD) (n=330). RESULTS: Total mortality was 3.9% (n=83), and no deaths were directly related to surgery. The cause of death was cardiac in 1.4% (n=30), non-cardiac in 2.3% (n=49), and unknown in 0.2% (n=4) of the patients. Mortality was premature (<30 days) in 38 patients (1.8%) and non-premature (>30 days) in 45 patients (2.1%). Total mortality was the same in Groups I and II (0.2%), and morbidity was 0.75%, and 0.9%, respectively. There were no premature deaths in these first 2 groups. In groups III and IV, mortality rose to 1.5% and 2% and morbidity to 0.9% and 1%. The total number of re-admissions (premature and non-premature) was higher in Groups III (6 re-admissions) and IV (9 re-admissions). The average total cost per patient, considering the sum of the average unit costs of the activities in each one of the medical processes which were studied (i.e., hospitalization, home visits, surgical activity, re-admissions, and second operations) was 117 euros in group I (ambulatory surgery) and 280 euros in group II (short stay). In both groups III and IV (hospitalization) the average total cost rose to 917.80 euros. CONCLUSIONS: Major ambulatory surgery may be an economical and efficient procedure for the health care system if it is used in carefully screened patients with cardiac stimulation.

Aged↗

PubMed2003

Histological evaluation of the effects of angiotensin peptides on wound repair in diabetic mice.

Recent studies have shown that angiotensin peptides accelerate dermal repair. Histological observation of samples taken at the termination of studies showed that the wounds treated with peptides were mature and organized by day 25 after full thickness excision in diabetic mice. However, the mechanisms by which this acceleration occurs has not been determined. In the experiments described here, the effect of angiotensin peptides (AII, A(1-7) and NorLeu (3)-A(1-7) on the quality of the healing wound was evaluated histologically. Administration of the peptides accelerated collagen deposition, re-epithelialization and new blood vessels formation. By day 4, the percentage of the wound with collagen increased two- to six-fold depending upon the peptide. The increase by angiotensin peptides continued throughout the experimental period. On days 4 and 7 9 (only) after injury, exposure to angiotensin peptides increased the number of blood vessels at wound site two-to three-fold. Finally, the percentage of the wound site covered with new epithelium increased after administration of angiotensin peptides. Re-epithelialization was observed as early as day 4 in wounds treated ith angiotensin peptides. The increase was greater at later time points (up to 8-fold ar day 14 with NorLeu(3)-A(1-7) had an increase in neutrophils and macrophages on day 4 after wounding. Overall, administration of these peptides resulted in a healing site that was more mature, including reorganization of the collagen into a basket-weave appearance. Further, these studies confirm the superiority of NorLeu(3)-A(1-7) to AII and A(1-7) in wound healing evaluated at a microscopic level.

Angiotensins↗

PubMed2004

[Aortic root homograft in the surgical treatment of aortic valve disease with dilated ascending aorta].

INTRODUCTION AND OBJECTIVES: Patients with aortic valve disease and a dilated ascending aorta are usually treated with a composite graft comprising a valve and conduit. We review here the results of treatment with an aortic root homograft as a valid alternative. PATIENTS AND METHOD: Twenty-two consecutive patients with a mean age of 64.8 (8.8) years were studied. Mean ascending aorta dilation was 54.55 mm, aortic valve insufficiency was present in 16 patients, and a combined lesion was present in 6. In all cases a cryopreserved aortic root homograft was used to replace the aortic valve and ascending aorta. In 9 cases a Dacron conduit was used beyond the sinotubular junction to restore continuity between the homograft and the native aorta. RESULTS: All patients survived surgery. One patient had postoperative systemic inflammatory response syndrome and one patient was re-explored for excessive bleeding. Mean duration of follow-up was 12.1 months (range 2-36 months). No patient was given anticoagulants, and one had an early transient cerebrovascular accident followed by complete recovery. At one month postsurgery the left ventricular systolic (P<.001) and diastolic (P<.009) diameters had decreased significantly on echocardiography, and these decreases persisted throughout follow-up. The caliber of the ascending aorta was normal in all patients (< or =30 mm) except one. CONCLUSIONS: Aortic root homografts are a valid alternative in the treatment of aortic valve disease with ascending aorta dilation. The main advantages of this therapy are that permanent anticoagulation is not needed, and that left ventricular dimensions recover rapidly.

Adult↗

PubMed1989

Coupled reactions for the determination of analytes and enzymes based on the use of luminescence.

Immobilized enzymes are widely used in the clinical laboratory in the assay of several analytes and enzymes. The use of immobilized enzymes makes these reagents recoverable and re-usable, and in most cases increases their stability and catalytic activity. In conjunction with bioluminescent enzymes (firefly and bacterial luciferases) and chemiluminescent catalyst (peroxidase) we set up high-sensitive flow methods based on the use of nylon tube coil or epoxy methacrylate column as solid support. All the NAD(P)/NAD(P)H-dependent dehydrogenases (bacterial luciferase), ATP-dependent enzymes (firefly luciferase) and oxidases producing H2O2 (peroxidase) can be immobilized and a large variety of analytes have been sensitively measured. As an alternative format we also reported a dry chemistry method in which all the enzymes, substrates and cofactors are ready to use, supported on dry cellulose disks. Methodological problems such as flow conditions, stability, pH, ionic strength and analytical performances are also reported.

Animals↗

PubMed1998

Glutamate, glutamine, and GABA as substrates for the neuronal and glial compartments after focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: Even though the utilization of substrates alternative to glucose may play an important role in the survival of brain cells under ischemic conditions, evidence on changes in substrate selection by the adult brain in vivo during ischemic episodes remains very limited. This study investigates the utilization of glutamate, glutamine, and GABA as fuel by the neuronal and glial tricarboxylic acid cycles of both cerebral hemispheres after partially reversible focal cerebral ischemia (FCI). METHODS: Right hemisphere infarct was induced in adult Long-Evans rats by permanent occlusion of the right middle cerebral artery and transitory occlusion of both common carotid arteries. (1,2-13C2) acetate was infused for 60 minutes in the right carotid artery immediately after carotid recirculation had been re-established (1-hour group) or 23 hours later (24-hour group). Extracts from both cerebral hemispheres were prepared and analyzed separately by 13C nuclear magnetic resonance and computer-assisted metabolic modeling. RESULTS: FCI decreased the oxidative metabolism of glucose in the brain in a time-dependent manner. Reduced glucose oxidation was compensated for by increased oxidations of (13C) glutamate and (13C) GABA in the astrocytes of the ipsilateral hemispheres of both groups. Increased oxidative metabolism of (13C) glutamine in the neurons was favored by increased activity of the neuronal pyruvate recycling system in the 24-hour group. CONCLUSIONS: Data were obtained consistent with time-dependent changes in the utilization of glutamate and GABA or glutamine as metabolic substrates for the glial or neuronal compartments of rat brain after FCI.

Acetates↗