Flow cytometric S-phase fraction as an independent prognostic indicator in colorectal liver metastases.
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Antigens, Nuclear↗
Biomedical subjects
A Russo
Publications and source records attributed to A Russo.
Afferent and efferent branching axons from the rat lumbo-sacral spinal cord project both to the urinary bladder and the urethra as demonstrated by double retrograde neuronal labeling.
A double retrograde axonal tracing technique has been used to ascertain the localization of neuronal cell bodies which give rise to branching axons innervating both the urinary bladder and the urethra in male rat. Application of fluorescent tracers Fast blue (FB) and Diamidino yellow (DY) to postganglionic fibers to the urinary bladder and to the urethra (penile nerve), respectively, produced the double-labeling of neurons located in the dorsal root ganglia and in the 'intermediolateral nucleus'.
Afferent Pathways↗
Stimulation by nitroxides of catalase-like activity of hemeproteins. Kinetics and mechanism.
The ability of stable nitroxide radicals to detoxify hypervalent heme proteins such as ferrylmyoglobin (MbFeIV) produced in the reaction of metmyoglobin (MbFeIII) and H2O2 was evaluated by monitoring O2 evolution, H2O2 depletion, and redox changes of the heme prosthetic group. The rate of H2O2 depletion and O2 evolution catalyzed by MbFeIII was enhanced by stable nitroxides such as 4-OH-2,2,6,6-tetramethyl-piperidinoxyl (TPL) in a catalytic fashion. The reduction of MbFeIV to MbFeIII was the rate-limiting step. Excess TPL over MbFeIII enhanced catalase-like activity more than 4-fold. During dismutation of H2O2, [TPL] and [MbFeIV] remained constant. NADH caused: (a) inhibition of H2O2 decay; (b) progressive reduction of TPL to its respective hydroxylamine TPL-H; and (c) arrest/inhibition of oxygen evolution or elicit consumption of O2. Following depletion of NADH the evolution of O2 resumed, and the initial concentration of TPL was restored. Kinetic analysis showed that two distinct forms of MbFeIV might be involved in the process. In summary, by shuttling between two oxidation states, namely nitroxide and oxoammonium cation, stable nitroxides enhance the catalase mimic activity of MbFeIII, thus facilitating H2O2 dismutation accompanied by O2 evolution and providing protection against hypervalent heme proteins.
Animals↗
Do nitroxide antioxidants act as scavengers of O2-. or as SOD mimics?
Stable nitroxide radicals were reported to act as SOD mimics and catalyze the dismutation of O2-. through two different catalytic pathways including reductive and oxidative reaction mechanisms (Samuni, A., Krishna, C. M., Riesz, P., Finkelstein, E. & Russo, A. (1988) J. Biol Chem. 263, 17921-17924). Recent studies directly monitoring O2-. and employing kinetics analysis did not reveal SOD activity of nitroxides (Weiss, R. H., Flickinger, A. G., Rivers, W. J., Hardy, M. M., Aston, K. W., Ryan, U. S. & Riley, D. P. (1993) J. Biol. Chem. 268, 23049-23054). Such discrepancy may result in cases where distinction of stoichiometric scavengers from catalytic detoxifiers of O2-. is not readily feasible. Nitroxides are effective antioxidants that protect against oxidative injury in various pathological processes. The distinction of their SOD mimic activity from O2-. scavenging was established by examining the validity of direct and indirect methods employed to assay SOD-like catalytic activity. Kinetics analysis along with direct EPR monitoring were used to study the mechanism underlying nitroxide reactions with O2-.. The nitroxide EPR signal decayed in the presence of NADH but otherwise did not decrease with time, thus substantiating its catalytic role in O2-. dismutation. The catalytic rate constants for O2-., dismutation, determined for the nitroxides tested, were found to increase with [H+], indicating that .OOH rather than O2-. is oxidizing the nitroxide. The results demonstrate the limitations associated with direct kinetics analysis in evaluating SOD mimic activity, underscoring the need for independent assays for valid discrimination of SOD mimics from stoichiometric scavengers of O2-..
Antioxidants↗
Nuclear DNA strand breaks during ethanol-induced oxidative stress in rat brain.
Free radical-mediated oxidative damage has been implicated in the pathophysiological mechanisms of apoptosis. In this study we report that statistically significant strand breaks were induced primarily in the hippocampus and cerebellum during chronic, and not acute, ethanol treatment. Damage to DNA observed in hippocampus and cerebellum was also correlated with significant modification in the activities of mitochondrial respiratory complexes I and IV and with a significant increase in lipid peroxidation products. This finding lends support to the fact that hippocampus and cerebellum are brain areas particularly vulnerable to redox changes induced by alcohol intoxication, suggesting lower threshold levels of ethanol tolerance.
Animals↗
A retrospective study of the effects of pelvic irradiation for gynecological cancer on anorectal function.
PURPOSE: To evaluate the prevalence of anorectal dysfunction following therapeutic pelvic irradiation. METHODS AND MATERIALS: Anorectal function was evaluated in 15 randomly selected patients (aged 47-84 years) who had received pelvic irradiation for treatment of carcinoma of the uterine body and cervix 5 and 10 years earlier. The following parameters were assessed in each patient: (a) anorectal symptoms (questionnaire), (b) anorectal pressures at rest and in response to rectal distension, voluntary squeeze, and increases in intraabdominal pressure (multiport anorectal manometry with concurrent electromyography of the anal sphincters), (c) rectal sensation (rectal balloon distension) and, (d) anal sphincteric morphology (ultrasound). Results were compared with those obtained in nine female control subjects. RESULTS: Ten of the 15 patients had urgency of defecation and 4 also suffered fecal incontinence. Basal anorectal pressures measured just proximal to the anal canal (p = 0.05) and anorectal pressures generated in response to voluntary squeeze measured at the anal canal were less (p < 0.01) in the patients. The fall in anal pressures in response to rectal distension was greater in the patients (p < 0.05) and the desire to defecate occurred at lower rectal volumes (p < 0.05). The slope of the pressure/volume relationship in response to rectal distension was greater (p < 0.05) in the patients, suggestive of a reduction in rectal compliance. In 14 of the 15 patients at least one parameter of anorectal motor function was outside the control range. There was no difference in the thickness of the anal sphincters between the two groups. CONCLUSION: Abnormal anorectal function occurs frequently following pelvic irradiation for gynecological malignant diseases and is characterized by multiple dysfunctions including weakness of the external anal sphincter, stiffness of the rectal wall, and a consequent increase in rectal sensitivity.
Adult↗
Phase II trial of 5-fluorouracil, leucovorin, interferon-alpha-2a, and cisplatin as neoadjuvant chemotherapy for locally advanced esophageal carcinoma.
BACKGROUND: Most patients with esophageal carcinoma present with locally advanced disease and a poor prognosis. Surgery or radiation provides palliation for locally advanced esophageal carcinoma. The role of neoadjuvant therapy remains to be defined. We administered neoadjuvant chemotherapy consisting of 5-fluorouracil (5-FU), leucovorin, interferon-alpha, and cisplatin to 11 patients with locally advanced disease. METHODS: Eleven patients with squamous cell or adenocarcinoma of the esophagus were treated peroperatively with two to three cycles of combination chemotherapy. Nine patients underwent resection with curative intent. RESULTS: Six patients received three cycles of chemotherapy, and five received two. Dose reduction was necessary for two patients. One patient achieved a pathologic complete response, histologically confirmed. Of the eleven patients, two did not undergo surgery because of progressive disease during chemotherapy. Seven of the 9 patients relapsed after surgery and 2 have been disease free for 27 months. CONCLUSIONS: The combination 5-FU leucovorin, interferon-alpha-2a, and cisplatin administered in a neoadjuvant setting resulted in a median survival of 11.8 months with a median time to relapse of 7 months.
Adult↗
Synthesis report of the step project detection of germ cell mutagens.
The project 'Detection of Germ Cell Mutagens' was designed with three major goals: (1) Detection and characterization of germ-cell mutagens; (2) standardization and validation of new germ-cell tests; and (3) development of a data base on germ-cell mutagenicity. All three goals were achieved. The classical germ-cell tests were applied to characterize the genetic effects of acrylamide (AA), 1,3-butadiene (BD), trophosphamide (TP) and urethane (UR). All but UR were found to cause heritable genetic damage. The experimental data obtained for AA and BD were the basis for genetic risk evaluations during the EC/US Workshop on Risk Assessment 'Human Genetic Risk from Exposure to Chemicals, Focusing on the Feasibility of the Parallelogram Approach'. Nine chemicals were employed to validate the spermatid micronucleus assay with mice and rats: AA, BD and its metabolites 1,2-epoxybutene-3 and 1,2:3,4-diepoxybutane, chlorambucil, mitomycin C, methylnitrosourea, TP and UR. The spermatid micronucleus test was combined with micronucleus tests in somatic cells such as bone marrow or peripheral blood erythrocytes, and splenocytes which allowed a comparison of effects in somatic and germinal cells. Improvements of the spermatid micronucleus test included BrdU-labelling of premeiotic S-phase for the determination of stage sensitivity and fluorescence in situ hybridization with pancentromeric DNA-probes to distinguish between clastogenic and aneugenic events. The results indicate that the spermatid micronucleus test with its improvements is an adequate procedure to detect germ-cell clastogenicity and to compare the activity of chemicals in different tissues and between species, i.e., rats and mice. Other germ cell methods under study were the flow cytometric measurement of testicular sperm DNA and the cytogenetic analysis of preimplantation embryos for chromosomal aberrations and micronuclei. The collection of a reliable germ-cell data base was accomplished through a critical evaluation of the literature and with the data obtained in the present project. Remarkable concordance between responses of germ cell tests to chemical mutagens was the most striking conclusion to be drawn from the present data base.
Acrylamide↗
Intake of macronutrients and risk of breast cancer.
BACKGROUND: The association between risk of breast cancer and dietary fat and intakes of other energy sources remains controversial. The Italian population offers special opportunities to assess the influence of high intakes of unsaturated fat and starch and, because the population has low awareness of diet and cancer issues, there is less scope for recall bias. We have assessed the relations of various macronutrient intakes with risk of breast cancer. METHODS: In this case-control study, 2569 women with incident breast cancer (median age 55 years) and 2588 control women (median age 56 years) in hospital with acute, non-neoplastic diseases, were interviewed in six different areas of Italy between 1991 and 1994. A validated food-frequency questionnaire was used. It included questions on 78 foods and recipes grouped into six sections, as well as specific questions on individual fat intake pattern. FINDINGS: The risk of breast cancer decreased with increasing total fat intake (trend p 0.01) whereas the risk increased with increasing intake of available carbohydrates (trend p = 0.002). The odds ratios for women in the highest compared with the lowest quintile of energy-adjusted intake were 0.81 for total fat and 1.30 for available carbohydrates. Starch was the chief contributor to the positive association with available carbohydrates. High intakes of polyunsaturated and unsaturated fatty acids (i.e., polyunsaturated fatty acids plus oleic acid) were associated with a decreased risk of breast cancer (odds ratios for highest vs lowest quintile 0.70 and 0.74, respectively). Conversely, the intakes of saturated fatty acids, protein, and fibre were not significantly associated with breast-cancer risk. INTERPRETATION: This case-controls study shows that unsaturated fatty acids protect against breast cancer, possibly because intake of these nutrients is closely correlated with a high intake of raw vegetables. The findings also suggest a possible risk in southern European populations, of reliance on a diet largely based on starch.
Adult↗
Tobacco and diet as determinants of survival in male laryngeal cancer patients.
In a series of 213 incident cases of laryngeal cancer, interviewed 10 years ago in the framework of a population-based case-control study, survival has been evaluated in relation to tobacco, alcohol consumption and dietary habits. The occurrence of other primaries and stage at diagnosis were taken into account as possible confounding factors. Heavy tobacco smoking appeared to worsen the prognosis in a dose-dependent manner. No effect was apparent for alcohol. The consumption of vegetables, citrus fruit, olive oil and orange juice was associated with a better prognosis; an opposite association was found for butter and milk. A tentative differentiation between dietary patterns showed a 36% advantage in survival for those whose dietary habits corresponded to the "Mediterranean diet". Our results support the hypothesis that diet may interfere with the mechanisms of cancer progression, and suggest that dietary intervention could be a means of improving survival in laryngeal cancer patients.
Case-Control Studies↗
Effects of the lipidosterolic extract of Serenoa repens (Permixon) on human prostatic cell lines.
BACKGROUND: Permixon is a drug used in the treatment of benign prostatic hyperplasia. We studied its androgenic and antiandrogenic effects in the prostatic cell lines LNCaP and PC3, respectively responsive and unresponsive to androgen stimulation. METHODS: We performed FACScan analysis to investigate toxicity, 3H thymidine and 35S methionine incorporation to determine antiproliferative and metabolic effects, electron microscopy to study ultrastructural changes and cotransfection experiments to elucidate the role of wild type androgen receptor. RESULTS: In LNCaP cell line, Permixon induced a double proliferative/differentiative effect, not observed in PC3 cells. In PC3 cells cotransfected with wild-type androgen receptors and CAT reporter genes under the control of a androgen responsive element, the drug inhibited androgen-induced CAT transcription. CONCLUSIONS: Our data indicate a role of the androgen receptor in mediating the effects of Permixon in LNCaP cells. Cotransfection experiments in PC3 cells support a clear antiandrogenic action of the drug.
Androgen Antagonists↗
A prospective, randomized trial comparing lymphoblastoid to recombinant interferon alfa 2a as therapy for chronic hepatitis C.
To compare the long-term effectiveness and tolerability of lymphoblastoid interferon (IFN-alphaN1) and recombinant interferon alfa 2a (IFN-alpha2a) in patients with chronic hepatitis caused by hepatitis C virus (HCV), 234 consecutive patients with HCV-related chronic hepatitis were randomized prospectively to receive titrated doses (starting dose = 6 million units [MU]) of IFN-alpha2a (n = 118) or IFN-alphaN1 (n = 116) for 12 months. HCV RNA was detected by reverse-transcription polymerase chain reaction (RT-PCR), quantified by branched-DNA (bDNA) assay, and genotyped by reverse hybridization assay. Thirty-one patients in the IFN-alpha2a group and 28 in the IFN-alphaN1 group (total, 59 [25%] had normal transaminases and undetectable HCV RNA by RT-PCR after 12 months of therapy, but only 19 in the first group and 20 in the second group (total, 39 [17%]) had biochemical and virological responses 12 months after treatment was discontinued. The two treatment groups differed in terms of prevalence of major drug-related adverse reactions (23% vs. 37%, P = .025). The mean total dose per patient was similar for the two groups, i.e., 502 MU IFN-alpha2a vs. 496 MU IFN-alphaN1, and the cost of each sustained response was $31,800 and $32,440, respectively. By multivariate analysis, pretreatment viremia higher than 0.2 MEq/mL and infection with genotype 1 were independently associated to treatment failure. The outcome of treatment in chronic hepatitis C patients was not improved by the administration of high cumulative doses of lymphoblastoid IFN.
Female↗
Improved delivery of biocontrol Pseudomonas and their antifungal metabolites using alginate polymers.
Alginate polymer was evaluated as a carrier for seed inoculation with a genetically modified strain Pseudomonas fluorescens F113LacZY, which protects sugar-beet against Pythium-mediated damping-off. F113LacZY survived in alginate beads at 5 log10 CFU/bead or higher counts for 8 weeks of storage, regardless of the conditions of incubation. In plant inoculation experiments, colonisation of the growing area of the root by F113LacZY, derived from alginate beads placed in the soil next to the seed or from an alginate coating around the seeds, was improved compared with application of just free cells of the strain. F113LacZY trapped in alginate beads was an effective producer of antifungal phloroglucinols as indicated by direct HPLC quantification of phloroglucinols and in vitro inhibition of both the indicator bacterium Bacillus subtilis A1 and the pathogenic fungus Pythium ultimum. Alginate polymer represents a promising carrier for the delivery of biocontrol inoculants for root colonisation and production of antifungal metabolites.
Alginates↗
Anatomical relationship between position of the sigmoid sinus and regional mastoid pneumatization.
In order to examine the relationship between the location of the sigmoid sinus (SS) and mastoid pneumatization, 25 adult temporal bones were dissected. Pneumatization was evaluated according to findings during dissections of three separate regions of the mastoid: i.e., the sinodural angle (SDA) area, inter-sinofacial area and mastoid apex. In addition, the SDA and distance between the SS and vertical portion of the facial nerve, were measured at the second genu (G) of the facial nerve, the junction (J) of the nerve and digastric ridge and the midpoint between G and J.A good correlation was observed between pneumatization of the cells surrounding the SDA and the distance between the SS and facial nerve at the mid-point of its vertical segment. However, pneumatization of the inter-sinofacial air cell tract could not be correlated with this distance. A significant decrease in the values of the SDA was found when the air cells surrounding the SDA were poorly pneumatized. This study indicated a correlation between the position of the SS and pneumatization of the mastoid in the area of the SDA.
Adult↗
The effect of acute hyperglycaemia on small intestinal motility in normal subjects.
The effects of hyperglycaemia on postprandial small intestinal motor activity are unclear. Duodenal and jejunal pressures and duodeno-caecal transit were measured in eight healthy male volunteers during euglycaemia (blood glucose 4-6 mmol/l) and hyperglycaemia (blood glucose 12-15 mmol/l). Duodenal and jejunal pressures were recorded with a manometric assembly during intraduodenal infusion of 100 ml nutrient liquid comprising 14% protein, 31.5% fat and 54.5% carbohydrate together with 15 glactulose. Duodeno-caecal transit was determined by a breath hydrogen technique. The number of duodenal (p < 0.05) and jejunal (p < 0.01) pressure waves, excluding phase III episodes was reduced during hyperglycaemia compared to euglycaemia Hyperglycaemia was associated with earlier onset of phase III activity (30 +/- 12 vs 132 +/- 20 min; p < 0.05) Duodeno-caecal transit was slower during hyperglycaemia when compared to euglycaemia (114 +/- 17 vs 49 +/- 6 min, p < 0.01). We conclude that induced hyperglycaemia has major effects on postprandial small intestinal motility. The reduction in duodenal and jejunal motor activity is likely to explain the retardation of small intestinal transit during hyperglycaemia.
Acute Disease↗
Stress proteins and SH-groups in oxidant-induced cell damage after acute ethanol administration in rat.
It is generally accepted that lipid peroxides play an important role in the pathogenesis of ethanol-induced cellular injury and that free sulfhydryl groups are vital in cellular defense against endogenous or exogenous oxidants. It has been observed that oxidative stress induces the synthesis of the 70-kDa family of heat-shock proteins (HSPs). Furthermore, induction of HSPs represents an essential and highly conserved cellular response to a variety of stressful stimuli. In the present study, we measured the intracellular levels of HSP 70 proteins after administration of mild intoxicating and grossly intoxicating doses of ethanol to rats. Our results demonstrate that elevated doses of ethanol induce HSP in various brain areas, namely, cerebellum, hippocampus, and to a lesser extent, striatum or liver. Induction of HSP 70 protein was correlated with a marked depletion of intracellular bound thiols and a decrease in lipid peroxidation measured as MDA formation. These studies support the hypothesis that a redox mechanism may be involved in the heat-shock signal pathway.
Alanine Transaminase↗
Regional wall motion analysis by dobutamine stess echocardiography to distinguish between ischemic and nonischemic dilated cardiomyopathy.
To distinguish between ischemic and nonischemic dilated cardiomyopathy (DCM), we studied 43 patients with left ventricular dysfunction (15 ischemic and 28 nonischemic detected by coronary angiography) by dobutamine stress echocardiography. At rest, there were more normal segments (p<0.001) and a trend toward more akinetic segments (p, not significant) per ischemic than per nonischemic DCM patient. However, either at rest or with low-dose dobutamine, individual data largely overlapped. At peak dose, in ischemic DCM, regional contraction worsened in many normal or dys-synergic regions at rest (in the latter case after improvement with low-dose dobutamine); in contrast, in nonischemic DCM, further mild improvement was observed in a variable number of left ventricular areas. Thus with peak-dose dobutamine, more akinetic and less normal segments were present per ischemic than per nonischemic DCM patient (both, p<0.001). A value of six or more akinetic segments was 80% sensitive and 96% specific for ischemic DCM. Our data show that analysis of regional contraction by dobutamine stress echocardiography can distinguish between ischemic and nonischemic DCM.
Aged↗
Increased circulating intercellular adhesion molecule-1 levels in type II diabetic patients: the possible role of metabolic control and oxidative stress.
Blood levels of the circulating form of the integrin intercellular adhesion molecule-1 (ICAM-1), malondialdehyde (MDA), and hemoglobin A1c (HbA1c) were studied at baseline and 3 months after improved metabolic control in 25 type II diabetic patients without signs of macroangiopathy, and were compared with those in 15 matched healthy normal controls. Circulating ICAM-1 and MDA levels were increased in diabetic patients, both at baseline and 3 months later. However, with improving metabolic control HbA1c, circulating ICAM-1, and MDA significantly decreased. A significant correlation between circulating ICAM-1, HbA1c, and MDA was found in diabetic patients at each time. Multiple regression analysis considering circulating ICAM-1 as the dependent variable and HbA1c and MDA as independent variables, showed a significant correlation between the three variable at each time. Similar correlations were found in control subjects. These data show increased levels of circulating ICAM-1 in type II diabetic patients, independent of the presence of macroangiopathy. Moreover, these results suggest that oxidative stress and metabolic control might participate in determining increased circulating ICAM-1 levels in both type II diabetic patients and normal subjects.
Diabetes Mellitus, Type 2↗