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P Rat

Publications and source records attributed to P Rat.

At least 37 records · Page 2Linked to original sources

[Intraperitoneal chemo-hyperthermia with "overflow" open abdomen].

The authors report an original procedure of open-abdomen intraperitoneal chemo-hyperthermia. The skin edges are watertightly stapled with a soft "abdominal cavity expander", supported by a Thompson self-retaining retractor positioned over the abdomen. So, the level of the liquid can be widely raised above the level of the skin edges. The anterior wall peritoneum, the wall edges are constantly exposed to the liquid. Large amplitude movements become possible: introduction into the abdomen of two forearms, even two arms, does not induce loss of any liquid. The small bowel, the stomach can be partially exteriorized. It becomes very easy to expose all the peritoneal spaces, to maintain an homogeneous hyperthermia within the abdomen, while using only one inflow drain, and one outflow drain.

Abdominal Neoplasms↗

[Radiation-induced cataract: physiopathologic, radiobiologic and clinical aspects].

Cataractogenesis is a widely reported late effect of irradiated crystalline lens. In this review the authors discussed the different aspects of radiation cataract pathogenesis, and the different mechanisms involved in the lens opacification, particularly the epithelium modifications such as epithelial cell death. The authors also reported the influence of radiation exposure on cataract formation following total body irradiation (TBI) and autologous or allogeneic bone marrow transplantation for hematologic malignancies. Moreover, the radiobiological parameters are not studied for the crystalline lens of human. We applied for the first time the linear-quadratic (LQ) and biological effective dose (BED) concept to TBI data. The calculated value of alpha/beta of 1 Gy is in the range of the values reported for the other late responding tissues. The other risk factors for cataract development after TBI such as age, gender, central nervous system boost, long-term steroid therapy and heparin administration are discussed. In terms of cataract or sicca syndrome prevention, numerous compounds have been successfully tested in experimental models or used for the prevention of radiation-induced xerostomia in patients treated for head and neck cancer. However, none of them has been clinically evaluated for ocular radiation late effects prevention. In this report the authors discussed some of the radioprotectors potentially interesting for radiation-induced cataract or sicca syndrome prevention.

Age Factors↗

Population-based study of factors influencing occurrence and prognosis of local recurrence after surgery for rectal cancer.

BACKGROUND: Few data are available from population-based statistics on the risk of local recurrence after surgery for rectal cancer. The aims of this study were to determine factors influencing local control and to analyse treatment and prognosis of recurrences in a well defined population. METHODS: Data were obtained from the cancer registry of the Côte d'Or (France). From 1976 to 1995, 682 patients resected for cure for a rectal carcinoma were included. Recurrence rates and survival rates were calculated using actuarial methods. A relative survival analysis and Cox multivariate analysis were performed. RESULTS: During the study 135 local recurrences were registered. The 5-year cumulative local recurrence rate was 22.7 per cent. In multivariate analysis the two variables significantly associated with local recurrence risk were stage at diagnosis and the macroscopic type of growth. There was a non-significant decrease in local recurrence rate in patients treated by preoperative radiotherapy compared with that in patients treated by surgery alone. The proportion of patients re-resected for cure was 25.2 per cent, and increased from 13.0 per cent in 1976-1985 to 37.9 per cent in 1986-1995 (P = 0.001). The 5-year relative survival rate was 13.6 per cent overall and 40.6 per cent after resection for cure (P < 0.001). CONCLUSION: Local recurrence of rectal cancer following resection remains a substantial problem. Improvement can be expected from better care and earlier diagnosis.

Adult↗

Pre-clinical study of the epinephrine-cisplatin association for the treatment of intraperitoneal carcinomatosis.

We have previously shown that intraperitoneal (i.p.) epinephrine enhances tumour penetration and anti-cancer activity of i.p.-administered cisplatin in rats with peritoneal carcinomatosis. Here, we show a direct correlation between the i.p. epinephrine concentration and cisplatin accumulation in rat peritoneal tumour nodules up to a concentration of 5 mg/l. This concentration leads to a maximal 3.7-fold increase of tumour platinum content and a maximal vasoconstriction of the peritoneal and tumour superficial microcirculation when registered by a laser doppler probe. Further, epinephrine half-life was 20.8+/-3.6 min in the peritoneal cavity of two laparotomized pigs. In these animals, epinephrine plasma concentration, heart rate and systolic blood pressure were dependent on the intraperitoneal dose of epinephrine, and life-threatening signs were not observed in either animal. In conclusion, a 5 mg/l concentration of epinephrine could be safely maintained in peritoneal fluid by regular replacement. This concentration is sufficient to maintain a constant vasoconstriction of the peritoneal and tumoral microvascular bed, and enhance the slow diffusion of cisplatin into peritoneal tumour nodules in the course of per-operative intraperitoneal chemotherapy.

Animals↗

Ocular surface changes induced by contact lens wear.

PURPOSE: To evaluate subclinical inflammation and mucus production of the conjunctiva in asymptomatic contact lens (CL) wearers, and to obtain an estimation of the chronologic variations in each group. METHODS: Eighteen eyes fitted with rigid CL (RCL) and 28 eyes with soft CL (SCL) worn daily were compared with 10 eyes from five healthy non-CL wearers. Impression cytology (IC) specimens were collected after clinical examination and were analyzed by flow cytometry using antibodies directed to HLA DR and intercellular adhesion molecule type 1 (ICAM-1) (CD 54), as inflammatory markers, and to the peptidic core of the conjunctival mucin (M1/MUC5AC) for mucus and goblet cell detection. The percentage of positive cells was calculated, and levels of fluorescence expression were quantified and compared between each group. RESULTS: A significant increase of HLA DR and ICAM-1 was observed in the SCL group in comparison with the control group. The two inflammatory markers were highly positively correlated with each other. Mucin detection with M1/MUC5AC did not find a significant difference between each group in terms of percentage of positive cells, but analyses of mean levels of fluorescence showed a significant decrease in the two CL groups. Evolution in time was different for each group, with a regular low level of inflammation in the RCL group in the first 10 years in comparison with the SCL group. In the SCL group, inflammation seemed to be higher before 2 years and after 10 years of wear. Mucin expression was variable in time, but without significant difference at any time. CONCLUSION: This study confirms difference in expression of subclinical conjunctival inflammation in asymptomatic CL wearers, with lower levels for RCL than SCL wearers with daily or extended wear. The mucin system is also modified by this low but chronic aggression of the ocular surface, with a tendency to decrease with time in the RCL and SCL groups.

Adult↗

Quaternary ammoniums and other preservatives' contribution in oxidative stress and apoptosis on Chang conjunctival cells.

PURPOSE: To investigate some of the toxicity mechanisms of 10 preservatives currently used in ophthalmic solutions in vitro. METHODS: A continuous human conjunctival cell line was treated with different concentrations of various preservatives for 15 minutes and for 15 minutes followed by 24 hours of cell recovery: three benzalkonium chlorides (BACs) with different hydrocarbon chain length, benzododecinium bromide (BOB), cetrimide (Cet), phenylmercuric nitrate (PM), thimerosal (thi), methyl parahydroxybenzoate (MPHB), chlorobutanol (clb), and EDTA. An inhibition study was then conducted using a 1-hour vitamin E pretreatment followed by a 15-minute BAC treatment. Membrane integrity was assessed using a neutral red test and chromatin condensation with a Hoechst 33342 test. Reactive oxygen species were measured using dichlorofluorescein diacetate test for H2O2 production and hydroethidine test for O2.- production. These tests were performed using microplate cold light cytofluorometry. Cell size and DNA content were also analyzed using flow cytometry. Confocal microscopy was used to explore morphologic changes. RESULTS: A significant decrease of membrane integrity with chromatin condensation was observed with all the quaternary ammoniums tested at concentrations of 0.005% and higher. The effect was amplified after 24 hours of cell recovery. The other preservatives tested did not decrease membrane integrity. H2O2 production was observed with all the preservatives, whereas O2.- production was significantly higher with the quaternary ammoniums at 0.005% and 0.01%, compared with the other preservatives. Flow cytometry results confirmed the cytotoxicity observed with cold light cytofluorometry. CONCLUSIONS: The quaternary ammoniums tested (BAC, BOB, and Cet) were the most cytotoxic preservatives in the current model. An apoptotic mechanism appeared to be present at low concentrations of quaternary ammoniums, whereas a necrotic process appeared at higher concentrations. Superoxide anions may play an important role in tissue damage induced by preservatives in ocular surface disorders.

Apoptosis↗

[Antioxidant effects of mast cell inhibitors in a human conjunctival cell line].

PURPOSE: The aim of this study was to evaluate in vitro antioxidant effects of two mast cells inhibitors. METHODS: Cytotoxicity tests were done on a continuous human conjunctival cell line using microplate cold light cytofluorimetry. Membrane integrity (neutral red test), DNA condensation (Hoechst 33342 test), and reactive oxygen species (ROS) production (dichlorofluoresceine diacetate and hydroethidine tests) were evaluated on living cells treated with sodium cromoglycate and N-acetyl-aspartyl glutamic acid (NAAGA) preserved (benzalkonium chloride: BAC at 0.01%) and unpreserved after 60 minutes of treatment or 60 minutes and 24 hours of cell recovery. They were tested pure and at a 1/10 dilution. ROS production was also evaluated after a 60 minute pretreatment with antiallergic drugs and a 15-minute treatment with BAC, according to previous experiments performed on BAC showing its ROS production properties. RESULTS: No cytotoxicity was observed with the unpreserved formulations of antiallergic drugs. An apoptotic phenomenom was suggested with preserved drugs after a 1-hour treatment, whereas a necrotic mechanism appeared after a 24-hour cell recovery period. A ROS production decrease was observed with the two preserved and unpreserved drugs tested (p<0.001 compared to BAC) even if it was significantly higher with cromoglycate formulations. A ROS production decrease also was detected after a pretreatment with antiallergic drugs and treatment with BAC (p<0.001 compared to BAC alone). CONCLUSION: In vitro, no cytotoxicity was found with the two unpreserved mast cell inhibitors tested. An antioxidant effect also was observed with these two molecules; sodium cromoglycate appeared to be the best free radical scavenger.

Anti-Allergic Agents↗

Mitochondrial activity and glutathione injury in apoptosis induced by unpreserved and preserved beta-blockers on Chang conjunctival cells.

PURPOSE: Quaternary ammonium ions have been demonstrated to induce apoptosis correlated with superoxide anion production in vitro. The purpose of this study was to further investigate the mechanisms of benzalkonium chloride (BAC), unpreserved and preserved beta-blocker eye-drops-induced programmed cell death, with special attention to the roles of mitochondrial transmembrane potential and intracellular reduced glutathione. METHODS: Chang conjunctival cells were incubated with different concentrations of unpreserved or preserved timolol (0.1%, 0.25%, and 0.4%), or carteolol (1% and 2%), or BAC (0.0001% to 0.01%) for 15 minutes, or for 15 minutes with a 24-hour recovery period in normal medium. Cellular viability (neutral red test), mitochondrial activity (rhodamine 123 test), intracellular reduced glutathione (monochlorobimane test), DNA condensation (Hoechst 33342 test), and reactive oxygen species (ROS) production (dichlorofluorescein diacetate and hydroethidine tests) were evaluated using microplate cold-light cytofluorometry. RESULTS: A significant, concentration-dependent decrease in cellular viability was found with preserved beta-blockers and with BAC alone, whereas unpreserved preparations did not show any toxicity. Only preserved beta-blockers induced chromatin condensation associated with an alteration of mitochondrial activity and a decrease of glutathione, suggesting an apoptotic phenomenon. BAC increased glutathione after 15 minutes, whereas a decrease was observed after a recovery period. ROS production was found with preserved formulations at significantly higher levels than those observed with unpreserved drugs. CONCLUSIONS: This in vitro study demonstrates that oxidative stress, evidenced by enhanced ROS production and mitochondrial injury rather than by cellular glutathione depletion, is a mechanism involved in apoptosis induced by preservative-containing eye-drops.

Adrenergic beta-Antagonists↗

Evidence of prooxidant and antioxidant action of melatonin on human liver cell line HepG2.

The aim of this study was to evaluate melatonin cytotoxicity by measuring its effects on various cellular targets. Cell viability, intracellular reduced glutathione (GSH) level, and reactive oxygen species (ROS) production were assessed in the human liver cell line (HepG2), after incubation with increasing melatonin concentrations (0.1-10,000 microM). The incubation times tested were 24, 72, and 96 h for cell viability and intracellular GSH level, and 15 and 45 minutes for ROS production. Cellular target evaluations were possible in living cells by means of a new microplate cytofluorimeter. This technology was suitable for the assessment of cell viability, GSH level, and ROS overproduction with, respectively, neutral red, monochlorobimane (mBCl), and 2',7'-dichlorofluorescin diacetate (DCFH-DA) fluorescent probes. At the lowest melatonin concentrations (0.1-10 microM) and for a relatively short incubation time (24 h), the antioxidant effect of melatonin was revealed by an increased intracellular GSH level, associated to cell viability improvement. In contrast, after longer incubation (96 h), cell viability significantly decreased with these lowest melatonin concentrations (0.1-10 microM). Moreover, high melatonin concentrations (1,000-10,000 microM) induced GSH depletion. This oxidative stress is associated with ROS overproduction from 10 microM after only 15 minutes of incubation. This dual effect is strong evidence that, in vitro, melatonin can be both antioxidant and prooxidant on the human liver cell line, depending on the concentration and incubation time.

Antioxidants↗

Ionizing radiation-induced death in bovine lens epithelial cells: mechanisms and influence of irradiation dose rate.

We recently reported, in a series of patients receiving total body irradiation before transplant, an influence of dose rate (DR) on cataract formation. The aim of our present in vitro study was to investigate the influence of DR and the mechanisms of lens cell death in a bovine model. After a single fraction of 10 Gy, delivered using low (0.05 Gy/min) or high (2 Gy/min) DR (LDR and HDR, respectively), cells were incubated in media supplemented with two different fetal calf serum (FCS) concentrations (1% and 10%). Cell proliferation was evaluated using Hoechst 33342 (HO) probe and cell viability, with neutral red probe. These fluorimetric assays used a cold light cytofluorimeter. After HO assay, stained cells were examined with fluorescence microscopy to evaluate the nuclear changes related to apoptosis. Global comparison of the mean HO fluorescent values observed with LDR/controls (c) vs. HDR/c revealed a significant difference only after 96 hr (P = 0.036). In 1% FCS conditions, the difference between HDR/c and LDR/c was also statistically significant at 96 hr (P = 0.04). Pairwise multiple comparison using values observed in 1% FCS conditions after 96 hr incubation showed significant difference between HDR vs. c (P = 0.001) and HDR vs. LDR (P = 0.007). This difference, in terms of fluorescence, was correlated to the proportion of cells with nuclear apoptotic morphology. In contrast, cell viability was not influenced by DR whatever the FCS concentration used, from 24 to 96 hr after irradiation. We conclude that our fluorimetric methodology is adapted to evaluate intracellular DNA modifications and cell viability after x-ray irradiation. We observed that a single fraction of 10 Gy induces in vitro lens epithelial cell apoptosis, which is influenced by DR. In humans, HDR is considered more cataractogenic than LDR. Thus, we speculate that lens cell apoptosis could be one of the major mechanisms of radiation-induced cataract. Further investigations are necessary to study the other possible mechanisms of cataractogenesis. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 138-144 (2000).

Animals↗

Improvement of operative mortality after curative resection for gastric cancer: population-based study.

It is not well known if the improvement in operative mortality after surgery for gastric cancer reported in hospital series can be extrapolated to the whole population. The aim of this study was to determine trends in operative mortality over a 20-year period in a nonselected community-based series of patients. A database of 648 patients with gastric cancer resected with curative intent between 1976 and 1995 in a region with a half-million population was divided into two periods: 1976-1983 and 1984-1995. Nonconditional logistic regression was performed to estimate the independent effects of the studied factors. Operative mortality was higher during the 1976-1983 period than during the 1984-1995 period (17.1% vs. 7.1%; p < 0.0001). When comparing the two study periods, operative mortality decreased dramatically from 26.2% to 10.0% in patients over age 70, from 31.8% to 7.9% after total gastrectomy, and from 30.7% to 6.3% after proximal esophagogastrectomy. Operative mortality after total gastrectomy was nearly the same as that after distal gastrectomy (7.9% vs 5.9%) during the second study period. During the first study period, operative mortality was independently associated with age at diagnosis, type of gastrectomy, and to a lesser degree stage at diagnosis; during the second study period, only age and stage at diagnosis were associated with the risk of operative mortality. This study indicates that in this well defined population operative mortality after curative resection for gastric cancer has decreased during the last 20 years. The results should encourage aggressive management of patients with gastric cancer, even in patients over 70 years of age.

Aged↗

Tubular duplication of the esophagus. Contribution of magnetic resonance imaging in anatomical analysis before surgery.

The authors report a tubular duplication of the thoracic esophagus in a 17-year-old male. This anomaly, rare in the adult, can be explained either by a failure of esotracheal compartmentalisation, or a notochordodysraphy or more probably by an error during vacuolisation of the esophagus. The anatomical characteristics of the duplication were clearly seen on MRI. This investigation showed the intramural duplication, with only a thin barrier without muscle, between the esophageal lumen and the duplication channel: two communications were present between the esophageal lumen and the duplication. The esophagus was accessed by right thoracotomy. The close contact between the duplication and the esophagus did not allow them to be separated. A subtotal esophagectomy was necessary, with digestive continuity being restored by coloplasty after a left cervicotomy and a laparotomy. The anatomy seen on the MRI should have predicted that an esophagectomy was necessary and that a thoracotomy could have been avoided by performing the procedure with a closed thorax.

Adolescent↗

Prognostic factors after curative resection for gastric cancer. A population-based study.

The aim of this study was to document patterns of survival after resection for cure for gastric cancer in a well-defined population. A population-based series of 649 gastric cancers resected for cure between 1976 and 1995 in a 494000 population, was used. Resection for cure was performed in 44.4% of the diagnosed cases. This proportion increased from 36.8% (1976-1979) to 45.0% (1992-1995) (P=0.03) whilst operative mortality decreased from 18.3 to 12.7% (P=0.003). The overall crude 5-year survival rate (excluding operative mortality) was 32.6% (95% confidence interval (CI) 28.7-36. 5) and the corresponding relative survival rate was 40.9%. Prognosis did not improve during the study period. Stage at diagnosis was the most important prognostic factor, the 5-year relative survival rate being 81.2% (+/-5.9) in TNM stage IA, 76.9% (+/-8.0) in stage IB, 50. 4% (+/-4.6) in stage II, 24.4% (+/-3.7) in stage IIIA, 5.6% (+/-3.2) in stage IIIB and 5.2% (+/- 2.2) in stage IV. Stage at diagnosis, age, subsite and macroscopic type of growth were independent prognostic factors, in a multivariate relative survival model. Earlier detection or development of an effective adjuvant therapy could contribute to improvement in prognosis.

Adolescent↗

Toxicity of preserved and unpreserved antiglaucoma topical drugs in an in vitro model of conjunctival cells.

PURPOSE: To compare the toxicity of a short-time application of timolol with benzalkonium chloride (timolol-BAC+) and unpreserved timolol (timolol-BAC-) in a human conjunctival cell line. METHODS: Chang's conjunctival cell line (ATCC CCL 20.2) was treated for 15min. with 0.1%, 0.25% or 0.4% timolol-BAC(+) or BAC(-) and then examined immediately or 24h later. Cell viability, chromatin condensation and free radicals production were studied by microplate cold light cytometry. Moreover, relative cell number was evaluated by crystal violet colorimetric test. The comparison was done with an oxidative stress model of cells treated with 0.001-0.000001% hydrogen peroxide (H(2)O(2)). In addition, cell size and the expression of an apoptotic marker Apo2.7 were evaluated by flow cytometry. RESULTS: Timolol-BAC(+) induced a rapid decrease in cell viability ranging from 40% immediately after treatment to 85% 24h later. A small initial decrease in cell viability was also observed with all tested concentrations of timolol-BAC(-) but, 24h later, cell viability either tended to remain constant or cells completely recovered. Cell viability fell down after 24h exposure to 0.001% H(2)O( 2) whereas it was not modified at lower concentrations. 24h after treatment with 0.25% timolol-BAC(+), the relative cell number was reduced by 55% whereas it did not vary after 0.25% timolol-BAC(-) treatment. Only timolol-BAC(+) induced chromatin condensation and cell size reduction. Moreover, cells treated with timolol-BAC(+) overexpressed the apoptotic marker Apo2.7. Both timolol-BAC(+) and BAC(-) induced reactive oxygen species (ROS) production which was significantly more important when 0.25% or 0.4% timolol-BAC(+) were applied. Only 0.001% and 0.0001% H(2)O(2) generated a significant free radicals production. CONCLUSION: In our model of conjunctival cells in vitro timolol-BAC(+) induced irreversible cytotoxic damage with some characteristics of apoptosis. The active compound of timolol-BAC(-) could be responsible for reactive oxygen species production and for cell viability variations. The role of oxidative stress in timolol-BAC(+)-induced toxicity seems not to be predominant. in vitro toxic effects of antiglaucoma drugs could, in part, explain some ocular surface disorders in long-term treated patients.

Adrenergic beta-Antagonists↗

[Toxicity of preserved and unpreserved beta-blocker eyedrops in an in vitro model of human conjunctival cells].

PURPOSE: To compare the toxicity of a short-time application of timolol with benzalkonium chloride (timolol-BAC+) and unpreserved timolol (timolol-BAC-) in an in vitro model of human conjunctival cells. METHODS: Chang's conjunctival cell line (ATCC CCL 20.2) was treated for 15min. with 0.1%, 0.25% or 0.4% timolol-BAC(+) or BAC(-) and then examined immediately or 24h later. Cell viability, chromatin condensation, mitochondrial mass and activity, free radicals production were studied by microplate cold light cytometry. Moreover, relative cell number was evaluated by crystal violet colorimetric test. In addition, cell size and the expression of an apoptotic marker Apo2.7 were studied by flow cytometry. RESULTS: Timolol-BAC(+) induced a rapid decrease in cell viability ranging from 40% immediately after treatment to 85% 24h later. A small, significantly less important decrease in cell viability was also observed with all tested concentrations of timolol-BAC(-). 24h after treatment with 0.25% timolol-BAC(+), the relative cell number was reduced by 55% whereas it did not vary after 0.25% timolol -BAC(-) treatment. Only timolol-BAC(+) induced chromatin condensation, decrease in mitochondrial membrane potential and cell size reduction. Moreover, cells treated with timolol-BAC(+) overexpressed the apoptotic marker Apo2.7. Also reactive oxygen species (ROS) production was significantly more important after cell exposure to timolol-BAC(+). CONCLUSION: In our model of conjunctival cells in vitro, timolol-BAC(+) induced irreversible cytotoxic damage with some characteristics of apoptosis. The active compound of timolol-BAC(-) could be responsible for ROS production and for cell viability variations. Oxidative stress could also play a role in timolol-BAC(+)-induced toxicity. In vitro toxic effects of antiglaucoma drugs could, in part, explain some ocular surface disorders in long-term treated patients.

Adrenergic beta-Antagonists↗

[Evaluation of free radical production by conjunctival impression cytology of patients treated with long-term antiglaucoma drugs or of contact lens wearers].

PURPOSE: To investigate free radical production in impression cytology specimens using microplate cold light cytofluorimetry. METHODS: 60 impression cytology specimens (IC) were harvested in 30 patients aged from 20 to 90 years. IC were taken in 10 healthy subjects, 10 glaucoma patients receiving longterm treatment for glaucoma and 10 contact lens wearers for more than five years. A complete ophthalmologic examination (BUT, corneal staining) was performed. Evaluation of free radical production was done using a dichlorofluoresceine diacetate (DCFHDA) test for H(2)O(2) evaluation and a hydroethidine test for O(2)(.)- measurement. RESULTS: The BUT values in the two pathological groups were significantly lower than those of controls (p<0.001). A free radical production was found in both contact lens wearers (p<0.001 compared to control values) and glaucoma patients (p<0.001 compared to control values). Both hydrogen peroxyde and superoxide anion productions were significantly correlated to the decrease of BUT values and the increase of superficial punctuate keratitis. CONCLUSION: The results of this preliminary study confirm that conjunctival epithelial cells may abnormally produce oxygen free radicals in chronic ocular surface disorders. This may participate to the cellular alterations observed in inflammatory diseases of ocular surface.

Adult↗

[Cytotoxicity evaluation of three tear substitutes used in the treatment of dry eye syndromes].

PURPOSE: To investigate cell tolerance of three tear substitutes used in the treatment of dry eye syndromes. METHODS: Cytotoxicity tests were done on a continuous human conjunctival cell line using microplate cold light cytofluorimetry. Membrane integrity, DNA condensation and reactive oxygen species (ROS) production (hydrogen peroxyde and superoxide anion) were evaluated after 15 minutes of treatment or 15 minutes and 24 hours of cell recovery. Hyaluronic acid, hydroxypropyl methylcellulose associated with sodium perborate (HPMC) and carbomer 934P were tested at their commercial concentrations (respectively 0.18%, 0.3% and 0.3%) and after a 1/10 dilution. RESULTS: Cell viability and chromatin condensation were not altered by hyaluronic acid for all concentrations and times tested. A decrease in membrane integrity was observed with 0.3% carbomer 934P after 24 hours of cell recovery and with 0.3% HPMC after 15 minutes. This decrease was amplified after 24 hours and associated with an apoptotic phenomenon. A H(2)O(2) production was observed with HPMC associated with sodium perborate and an O(2) production was found with hyaluronic acid diluted at 1/10. CONCLUSION: Hyaluronic acid, carbomer and HPMC are in vitro well-tolerated even if HPMC induces a more important decrease of cell viability compared to the other drugs. Hyaluronic acid, with its rheologic properties, with no in vitro toxicity, seems to be efficient for dry eye patients.

Borates↗

[The effect of intra-abdominal temperature on the tissue and tumor diffusion of intraperitoneal cisplatin in a model of peritoneal carcinomatosis in rats].

OBJECTIVE: To evaluate the effects of hyperthermia and hypothermia on the peritoneal and on tumor penetration by intraperitoneal cisplatin. MATERIAL AND METHODS: Twenty day old peritoneal carcinomatosis was obtained after intraperitoneal injection of 1 x 10(6) DHD/K12/PROb cells into BD IX rats. Animals were treated by intraperitoneal infusion of cisplatin (25 micrograms/mL) using hyperthermic (16.6 degrees C), normothermic (37.6 degrees C) or hyperthermic (41.8 degrees C) intraperitoneal chemotherapy. RESULTS: Hyperthermia increased cisplatin concentration in tumoral and diaphragmatic tissues compared to normothermic treatment, while renal concentrations were lower. Hypothermia produced lower cisplatin concentrations in both cancer and peritoneal tissues compared to normothermic treatment. CONCLUSION: These experiments confirmed the pharmacological advantage produced by hyperthermia in cisplatin intraperitoneal chemotherapy.

Abdomen↗