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Biomedical subjects

A Russo

Publications and source records attributed to A Russo.

At least 487 records · Page 27Linked to original sources

Superoxide reaction with nitroxides.

Stable, free radical nitroxides are commonly used ESR spectroscopy tools. However, it has recently been found that ESR observable signal from 5-membered ring spin-adducts or stable label nitroxides is lost or diminished by reaction with superoxide. A similar radical-radical annihilation was not found for six membered ring nitroxide radicals. To discern why six-membered ring nitroxides are not reduced under superoxide flux generated by hypoxanthine/xanthine oxidase, spectrophoptmetric (Cyt CIII) and chemiluminescence (lucigenin) and ESR assays were used to follow the reactions. Spectrophotometry and chemiluminescence clearly demonstrated that the six-membered piperidine-1-oxyl compounds (TEMPO, TEMPOL, and TEMPAMIN) rapidly react with superoxide: rate constants at pH 7.8 ranging from 7 x 10(4) to 1.2 x 10(5) M-1 s-1. The absence of detectable ESR signal loss results from facile re-oxidation of the corresponding hydroxylamine by superoxide. To fully corroborate the efficiency of the 6-membered nitroxide superoxide dismutase activity, they were shown to protect fully mammalian cells from oxidative damage resulting from exposure to the superoxide and hydrogen peroxide generating system hypoxanthine/xanthine oxidase. Since six-membered cyclic nitroxides react with superoxide about 2 orders of magnitude faster than the corresponding 5-membered ring nitroxides, they may ultimately be more useful as superoxide oxide dismutase mimetic agents.

Animals↗

Response of black and white guinea pig skin to photodynamic treatment using 514-nm light and dihematoporphyrin ether.

Differences in skin pigmentation may significantly affect light penetration during photodynamic therapy. This study evaluated the effect of skin pigmentation on dermatotoxic reaction to photodynamic therapy utilizing the photosensitizer dihematoporphyrin ether. Black and white guinea pigs were given 10 mg/kg of dihematoporphyrin ether, depilated, and treated 48 hours after injection with 30 mW/cm2 of 514-nm light. Eschar formation was observed on white skin at an average light dose of 26 J/cm2, whereas black skin showed similar changes at 58 J/cm2. Microscopically, superficial necrosis corresponded to the gross changes noted. Our results agree with data describing the difficulty of treating pigmented lesions such as malignant melanoma with photodynamic therapy. This further suggests that higher light doses may be required to treat superficial lesions and produce skin photosensitivity in dark-skinned individuals.

Animals↗

Cardiovascular disease risk factor reduction and the occupational health nurse.

The occupational health nurse should be attuned to issues and research regarding prevention of CVD. Risk reduction programs in industry should adhere to the recommendations of groups such as the Adult Treatment Panel of the National Cholesterol Education Program, the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure, and the American Health Association. Despite significant reductions in CVD mortality, continued research is needed to further our knowledge of CVD risk factors among high risk populations.

Cardiovascular Diseases↗

Free radicals induced by adriamycin-sensitive and adriamycin-resistant cells: a spin-trapping study.

The radicals generated by adriamycin-sensitive (CHO-AB) and adriamycin-resistant (CHO-C5) Chinese hamster ovary cells as well as by adriamycin-sensitive and -resistant human breast cancer cells (MCF7-WT and MCF7-ADR) have been studied with spin-trapping and ESR spectroscopy. During anoxic exposure to adriamycin (ADR) both pairs of cell lines produced the broad ESR singlet characteristic of ADR semiquinone (AQ.). By use of tris(oxalato)chromate (CrOx) as an extracellular line-broadening agent, the distribution of AQ. between the intra- and extracellular compartments was studied. For cell densities of (1-3) X 10(7) cells/mL, CrOx eliminated most, though not all, of the ESR signal, indicating that the AQ. radicals freely diffuse and partition between the intra- and extracellular compartments proportionally to their respective volumes. Similar behavior was exhibited by all four cell lines studied. Upon introduction of oxygen to anoxic cells in the presence of the spin trap 5,5-dimethylpyrroline N-oxide (DMPO), the AQ. signal was replaced by that of the DMPO-OH spin adduct. Metal chelators such as desferrioxamine had no effect on DMPO-OH or AQ. formation. Superoxide dismutase, not catalase, totally eliminated the ESR signal, indicating that DMPO-OH produced by ADR-treated cells originates from superoxide rather than from .OH produced from H2O2. In the presence of CrOx, the DMPO-OH signal was not distinguishable from the background noise, thus excluding any contribution to the signal by intracellular spin adducts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Screening for liver metastases of colorectal carcinoma by the routine use of intraoperative echography].

The detection and distribution of liver metastases from colorectal carcinoma is an important problem for the therapeutic approach and prognosis. In this study we evaluated the diagnostic accuracy and technical utility of intraoperative ultrasonography (I.O.U.) in the treatment for liver metastases from colorectal carcinoma. I.O.U. has been routine performed in 70 patients. 13 metastatic lesions have been diagnosed in 10/70 patients with colorectal carcinoma (14.3%). Only 6 of 13 lesions (sensitivity of 46.1%) have been diagnosed preoperatively and/or by surgical exploration. Instead 7 small intrahepatic metastatic lesions (53.9%) have been diagnosed exclusively by I.O.U. It has not been possible to detect this lesions by surgical exploration; the size of these metastatic tumor ranged from 0.4 x 0.6 to 1.2 x 1.6 cm. I.O.U. has been useful for its high sensitivity, for the study of anatomic relation between metastatic lesions and vascular and biliary hepatic structure (good guidance for surgical hepatic resection) and for the possibility of performing deep ultrasound guided biopsies of hepatic lesions.

Carcinoma↗

Branching projections from subcoeruleus area neurons to medial preoptic area and cervical spinal cord revealed by double retrograde neuronal labeling.

In this study we utilized a double retrograde axonal tracing technique to investigate the possible existence of collateralized axonal projections of subcoeruleus area neurons to both 'medial preoptic area (MPA) and cervical (C1-C3) spinal cord'. Following microinjections of fluorescent tracers (Fast blue (FB) and Diamidino yellow (DY) within MPA and C1-C3, substantial numbers of FB and DY single-labeled neurons as well as FB-DY double-labeled branched neurons have been found within subcoeruleus area.

Amidines↗

Inferences on the inheritance of congenital anomalies from temporal and spatial patterns of occurrence.

Most congenital anomalies are believed to result from interactions between genetic and environmental determinants, whose relative importance is not generally established. Temporal and spatial patterns allow inferences on the underlying transmission processes; in particular, it is possible to discriminate between sporadic and nonsporadic genetic factors, and to find evidence for the effects of environmental heterogeneity in time and space. We studied the occurrence of 14 anomalies in 14 registries of Western Europe. Four basic patterns have been identified: (1) Chromosomal abnormalities have uniform incidences and do not show significant geographical variation, in agreement with the expected consequences of randomly scattered nondisjunction events. (2) The homogeneous spatial distributions of three severe malformations (renal agenesis, oesophageal atresia, ano-rectal atresia) are consistent with both the effects of fresh mutation and segregation of detrimental alleles. (3) A decrease of similarity of incidences with distance has been observed for neural tube defects, and this is the expected consequence of isolation by distance on genetically determined traits. (4) For facial clefts, polydactyly, and hypospadias, all postulated processes poorly account for the observed temporal and spatial patterns.

Adult↗

Role of intraoperative ultrasound in the screening of liver metastases from colorectal carcinoma: initial experiences.

The aim of this study was to assess the utility of intraoperative ultrasound (IOUS) in the diagnosis and management of liver metastases from colorectal carcinoma. IOUS was performed on a consecutive series of 70 patients undergoing surgery for colorectal carcinoma, with follow-up ranging from 6 to 24 months. In ten cases (14.3%), 13 metastatic tumours were diagnosed; only six of these had been found by preoperative workup and/or surgical inspection. Seven (53.9%) small metastatic liver lesions were identified only by IOUS. None of the lesions diagnosed by IOUS was palpable, and they were all extremely small--ranging from 4 x 6 to 12 x 16 mm. Seventy-three locations were examined in order to compare the results of IOUS with those of other methods. The sensitivity of the former proved to be higher (P less than .05) than that of conventional pre- and intraoperative screening.

Carcinoma↗

Cis-diamminodichloroplatinum plus a 5-day continuous infusion of 5-fluorouracil in the treatment of locally recurrent and metastatic head and neck cancer patients.

A group of 23 consecutive patients with biopsy-proven advanced or metastatic head and neck cancer were treated with cisplatinum, 100 mg/m2 i.v., on day 1 plus 5-fluorouracil, 1000 mg/m2, in continuous infusion for 5 days. Most patients (87%) had recurrent or metastatic cancer and were previously treated (78%). Out of 21 evaluable patients we obtained a 42% overall response rate (complete + partial responses) with a mean duration of more than 8 months and a 14% minimal response rate. A stabilization of disease was achieved in 28% of cases, while 14% of patients progressed. This response rate, as well as the duration of response, seems to be similar to those obtained in other series comprising previously treated patients with advanced or metastatic head and neck carcinoma. The toxicity was generally acceptable, with few cases of grade 3 (WHO criteria) toxicity. However most patients required hospitalization because of the length of treatment. In conclusion the response rate and the duration of responses obtained with cisplatinum plus a 5-day infusion of 5-FU in advanced or metastatic pretreated patients is, at present, unsatisfactory, even if the impact on survival is still not entirely clear.

Adult↗

Bronchoscopic phototherapy at comparable dose rates: early results.

Photodynamic therapy is a recently introduced treatment for surface malignancies. Since January 1987, 10 patients with endobronchial neoplasms have had bronchoscopic photodynamic therapy at similar dose rates (400 mW/cm) for total atelectasis (2), carinal narrowing with respiratory insufficiency (2), or partial obstruction without collapse (4). Two patients underwent photodynamic therapy as a preliminary to immunotherapy. Histologies included endobronchial metastases (colon, ovary, melanoma, and sarcoma, 1 each; and renal cell, 3) and primary lung cancer (3). The 2 patients with total atelectasis had complete reexpansion after photodynamic therapy, which permitted eventual sleeve lobectomy in 1. Carinal narrowing was ameliorated in the 2 patients seen with inspiratory stridor, thereby permitting hospital discharge. Endoscopically resected fragments after photodynamic therapy exhibited avascular necrosis. These data support further controlled studies of photodynamic therapy by thoracic surgical oncologists to define its limitations as well as to improve and expand its efficacy as a palliative or surgical adjuvant.

Adult↗

In vitro photodynamic therapy of human lung cancer.

Photodynamic therapy (PDT) using a dihematoporphyrin ether (DHE) sensitizes malignant cells to damage by 630-nm light. This study investigated in vitro PDT sensitivity of human lung cancer cells (A549) and those factors which influence cell survival as determined by the colony formation assay. After incubation for 2, 4, or 6 hr with [DHE] of 2.5, 25, or 50 micrograms/ml, A549 received red light at dose rates of 0.27 or 0.09 mW/cm2 and energies of 0-250 mJ/cm2. Neither 630-nm light alone nor DHE alone affected cell survival. A dose rate of 0.27 mW/cm2 required less energy than 0.09 mW/cm2 for 90% cytotoxicity (180 mJ/cm2 vs 250 mJ/cm2, P less than 0.05). The energy required for 90% cytotoxicity with 25 micrograms/ml [DHE] was dependent on DHE incubation time (2 hr, 90% cytotoxicity not reached; 4 hr, 116 mJ/cm2; 6 hr, 69 mJ/cm2; P less than 0.05). In contrast, cellular [DHE] as measured by fluorescence, plateaued after 2 hr of incubation. Fluorescence microscopy revealed a time-dependent redistribution of fluorescence from the cell membrane to perinuclear and intracytoplasmic organelles. A 99% cytotoxicity required significantly less energy as [DHE] was increased (2.5 micrograms/ml, no cytotoxicity; 25 micrograms/ml, 243 mJ/cm2; 50 micrograms/ml, 111 mJ/cm2; P less than 0.05). Intracellular [DHE] was directly dependent on the incubating media [DHE] (2.5 micrograms/ml, 0.09 +/- 0.01 micrograms/10(6) cells; 25 micrograms/ml, 0.80 +/- 0.07 micrograms/10(6) cells; 50 micrograms/ml, 1.31 +/- 0.11 micrograms/10(6) cells; P less than 0.05). PDT cytotoxicity was inversely proportional to concentration of serum in the DHE media. These data illustrate that lung cancer in vitro is sensitive to PDT and is influenced by dose rate, energy input, and DHE environmental manipulations. These factors may be important in increasing the efficiency of PDT of thoracic malignancies in vivo.

Carcinoma↗

Potentiation of phototherapy cytotoxicity with light scattering media.

Lung cancer cells are susceptible to photodynamic therapy (PDT) using 630 nm light and dihematoporphyrin ether (DHE). A light scattering media, intralipid (IL), was compared to balanced salt solution (PBS) for PDT of A549 human lung cancer cells. Differences in cellular DHE content after IL or PBS exposure were determined. Cells were incubated in 25 micrograms/ml DHE for 2 hr and then incubated in various concentrations of IL or PBS at room temperature for 2.5 to 10.0 min. Significant amounts of DHE were lost from IL-incubated cells compared to cells incubated in PBS. After 5 min in 1% IL, cellular DHE content was 0.32 +/- 0.04 microgram DHE/10(6) cells compared to 0.56 +/- 0.11 microgram DHE/10(6) cells in PBS-incubated cells (P less than 0.05). Despite this, superior PDT cytotoxicity was noted when cells were treated in IL with energy densities greater than or equal to 105 mJ/cm2. At an energy density of 210 mJ/cm2, the survival fraction (SF) of cells treated in 1% IL was 0.004 +/- 0.001 compared to 0.071 +/- 0.022 in PBS-treated cells (P less than 0.05). SF was dependent upon the IL concentration with the greatest cell killing noted with 1% IL. An apparent loss of cellular DHE ("DHE washout") was confirmed by demonstration of a higher SF of cells incubated in IL, rinsed, and subsequently PDT-treated in PBS with 157.5 mJ/cm2 (SF = 0.85 +/- 0.11) compared to cells incubated and treated in PBS (SF = 0.50 +/- 0.03, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Survival↗

Lack of induction of somatic aneuploidy in the mouse by nitrilotriacetic acid (NTA).

Nitrilotriacetic acid (NTA) was tested for the induction of aneuploidy in mouse bone marrow cells. Doses of 138 or 275 mg/kg of body weight were intraperitoneally injected 24 h after implantation of a bromodeoxyuridine tablet. Cell-replication kinetics was assessed by comparing the relative percentages of first, second and third metaphases in control and treated samples. The hyperploidy incidence was estimated in second metaphases only, together with the SCE/cell level. Mice injected with 1.8 mg/kg vinblastine (VBL) were used as positive controls. A slight delay of cell cycle was induced by NTA, as shown by regression analysis applied to average generation time values. No increase over the control level was observed for hyperploidy or SCE induction in NTA-treated mice. VBL induced both cell-cycle alteration and a highly significant (P less than 0.001) increase of the hyperploid cell frequency. On the basis of these and previous (Costa et al., 1988) observations it seems that the non-disjunctional activity of NTA in the mouse is confined to meiotic processes.

Acetates↗

Glutathione modulation in cancer treatment: will it work?

Glutathione (GSH) assumes a pivotal role in numerous cellular functions including bioreductive reactions, maintenance of enzyme activity, amino acid transport, protection from harmful oxidative species, and detoxification of xenobiotics. The importance of GSH in modifying the cellular response to several anti-cancer treatment modalities has become better appreciated with the introduction of agents which can either decrease or elevate GSH levels in cells and tissues. In general, GSH depletion has been demonstrated to further enhance the cytotoxicity of several chemotherapy drugs and nitroimidazole hypoxic cell radiosensitizers. Conversely, GSH elevation affords varying degrees of protection. Whether or not GSH modulating agents will be useful as an adjuvant to selected cancer treatment modalities will depend on whether differential levels of GSH can be achieved in tumor versus normal tissues. Accurate GSH measurements in tumor and normal tissues will be required to adequately use and interpret the results of clinical studies where GSH modulating agents are employed. Precise tumor GSH measurements pose a considerable challenge due to the complicated cellular makeup of tumors.

Antineoplastic Agents↗

Use of monochlorobimane for glutathione measurements in hamster and human tumor cell lines.

The use of monochlorobimane (MCIB) as a fluorescence label for glutathione (GSH) quantitation was investigated in human tumor cell lines. When MCIB was used with a hamster fibroblast cell line under conditions where GSH was either depleted or elevated, an excellent correlation between bimane-GSH fluorescence and the standard cyclic GSH reductase assay (Tietze's) was accomplished. When the MCIB technique was applied to a human lung adenocarcinoma cell line, little or no GSH labeling was noted even at MCIB levels 10X higher than that used for the hamster line. HPLC analysis suggested that the source of the problem may be the affinity for MCIB to glutathione S-transferase. By using higher dye concentrations and longer staining times, adequate staining was possible. While the MCIB technique may have problems quantitating GSH levels between cell types, the possibility of examining GSH heterogeneity in solid tumor biopsies remains feasible.

Animals↗