ABSTRACT
Background Cortical multiple sclerosis lesions are clinically relevant but inconspicuous at conventional clinical MRI. Double inversion recovery (DIR) and phase-sensitive inversion recovery (PSIR) are more sensitive but often unavailable. In the past 2 years, artificial intelligence (AI) was used to generate DIR and PSIR from standard clinical sequences (eg, T1-weighted, T2-weighted, and fluid-attenuated inversion-recovery sequences), but multicenter validation is crucial for further implementation. Purpose To evaluate cortical and juxtacortical multiple sclerosis lesion detection for diagnostic and disease monitoring purposes on AI-generated DIR and PSIR images compared with MRI-acquired DIR and PSIR images in a multicenter setting. Materials and Methods Generative adversarial networks were used to generate AI-based DIR (n = 50) and PSIR (n = 43) images. The number of detected lesions between AI-generated images and MRI-acquired (reference) images was compared by randomized blinded scoring by seven readers (all with >10 years of experience in lesion assessment). Reliability was expressed as the intraclass correlation coefficient (ICC). Differences in lesion subtype were determined using Wilcoxon signed-rank tests. Results MRI scans of 202 patients with multiple sclerosis (mean age, 46 years ± 11 [SD]; 127 women) were retrospectively collected from seven centers (February 2020 to January 2021). In total, 1154 lesions were detected on AI-generated DIR images versus 855 on MRI-acquired DIR images (mean difference per reader, 35.0% ± 22.8; P < .001). On AI-generated PSIR images, 803 lesions were detected versus 814 on MRI-acquired PSIR images (98.9% ± 19.4; P = .87). Reliability was good for both DIR (ICC, 0.81) and PSIR (ICC, 0.75) across centers. Regionally, more juxtacortical lesions were detected on AI-generated DIR images than on MRI-acquired DIR images (495 [42.9%] vs 338 [39.5%]; P < .001). On AI-generated PSIR images, fewer juxtacortical lesions were detected than on MRI-acquired PSIR images (232 [28.9%] vs 282 [34.6%]; P = .02). Conclusion Artificial intelligence-generated double inversion-recovery and phase-sensitive inversion-recovery images performed well compared with their MRI-acquired counterparts and can be considered reliable in a multicenter setting, with good between-reader and between-center interpretative agreement. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Zivadinov and Dwyer in this issue.
Subject(s)
Multiple Sclerosis , Humans , Female , Middle Aged , Multiple Sclerosis/diagnostic imaging , Multiple Sclerosis/pathology , Artificial Intelligence , Retrospective Studies , Reproducibility of Results , Magnetic Resonance Imaging/methodsABSTRACT
OBJECTIVE: verification of a hypothesis assuming that 5-HT3 receptor blockade by intravenous administration of ondansetron reduces the incidence of hypotension and bradycardia in patients undergoing spinal anaesthesia for Caesarean section. MATERIAL AND METHODS: The study design was approved by the Bioethics Committee and included 72 patients undergoing elective Caesarean section, randomly assigned to ondansetron group (group 0) or placebo group (group P). Finally group 0 encompassed 35 patients administered ondansetron 8 mg i.v. dissolved in 10 ml 0.9% NaCl whereas group P consisted of 34 patients receiving 0.9% NaCl 10 mg. Systolic and diastolic pressures were measured every 2 minutes since the onset of anaesthesia. Heart rate (HR) was monitored continuously The criterion of hypotension requiring ephedrine was a decrease in systolic pressure by 20% compared to its baseline value or a decrease in systolic pressure below 90 mm Hg. The criterion of bradycardia was a decrease in HR below 60/min. RESULTS: Hypotension was observed in 14 group 0 patients (39%) and in 15 group P patients (44%); the difference was not statistically significant. Bradycardia was noted in 1 group 0 patient (3%) and in 2 group P patients (6%); the difference was not statistically significant. CONCLUSION: A hypothesis assuming a reduction in pressure following subarachnoid anaesthesia for Caesarean section after the administration of 8 mg of ondansetron was not confirmed.
Subject(s)
Antiemetics/administration & dosage , Cesarean Section/adverse effects , Hemodynamics/drug effects , Hypotension/prevention & control , Ondansetron/administration & dosage , Blood Pressure/drug effects , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Hypotension/etiology , Infant, Newborn , Injections, Intravenous , Pregnancy , Treatment OutcomeABSTRACT
The aim of this study was to determine residual polychlorinated biphenyls (PCBs) and organochlorine pesticides in the adipose tissue of wild terrestrial mammals coming from the same area in northwest Poland and to compare the organochlorine content and profile between species. The study was performed on five mammalian species, including omnivores (badger, wild boar, raccoon dog) and herbivores (roe deer, red deer). The obtained results show that the levels of residues of most of the analyzed compounds were greater in omnivorous mammals than herbivorous mammals. We found differences in the pattern of accumulation of organochlorines. In the raccoon dog organochlorines accumulated in the following descending order: DDTs > PCBs > HCHs > endrin > dieldrin; in the badger, wild boar, and roe deer, the order was as follows: DDTs > HCHs > PCBs > endrin > dieldrin; and in red deer, the order was as follows: HCHs > DDTs > PCBs > endrin > dieldrin. PCB 153 was dominant in herbivores and in the wild boar, whereas in the raccoon dog it was lower than PCB 138 and in badger lower than PCB 180. These differences in the tested species may reflect differences in metabolic capacity and/or feeding habits and an uneven distribution of organochlorines in the area where the animals lived. Maximum residue levels (MRLs) were exceeded in single samples from animals whose meat and fat can be consumed by humans. The greatest number of cases where MRLs were exceeded was observed in the adipose tissue of the badger (HCHs, DDTs, endrin, non-dioxin-like PCBs) and the fewest in the adipose tissue of roe deer (only lindane).
Subject(s)
Environmental Monitoring , Environmental Pollutants/metabolism , Hydrocarbons, Chlorinated/metabolism , Mammals/metabolism , Adipose Tissue/metabolism , Animals , PolandABSTRACT
The aim of this study was to detect the presence and determine the residue levels of DDT, lindane, endrin and polychlorinated biphenyls (PCBs) in the liver of wild boars from the area of West Pomerania, NW Poland; to determine the activity of glutathione S-transferase (GST) as a biomarker of biological response and to assess the toxicological risk for consumers of the wild boar offal. The presence of pesticide residues and PCBs was found in all examined liver samples. The highest concentration was observed for endrin, and then, the descending order was PCBs >DDTs >lindane >dl-PCBs. The mean hepatic concentrations of endrin, PCBs, DDTs and lindane were 117.28, 78.59, 67.95 and 7.24 ng/g lipid weight, respectively. Among the dioxin-like PCB congeners, 118 and 156 were dominant in liver samples. The mean toxic equivalent (TEQ) level calculated for dl-PCBs was 2.10 ± 1.11 pg WHO-PCB-TEQ/g. There was a statistically significant (p < 0.05) negative correlation between the concentration of lindane, DDTs and PCBs (as a sum of indicator congeners) in the liver and in the activity of GST. However, GST activities showed no significant correlation with any of the dl-PCBs. In five boar liver samples, the levels of certain organochlorine compounds exceeded the maximum residue levels (MRLs). In one sample, the MRLs were exceeded simultaneously for PCBs, endrin and DDTs and in another one-for endrin and DDTs. In the remaining three samples, only PCB levels were exceeded.
Subject(s)
Environmental Monitoring/methods , Hydrocarbons, Chlorinated/metabolism , Sus scrofa/metabolism , Animals , Biomarkers/metabolism , Female , Glutathione Transferase/metabolism , Male , Poland , Polychlorinated Biphenyls/metabolism , SwineABSTRACT
The Hildebrand solubility parameters have been calculated for eight ionic liquids. Retention data from the inverse gas chromatography measurements of the activity coefficients at infinite dilution were used for the calculation. From the solubility parameters, the enthalpies of vaporization of ionic liquids were estimated. Results are compared with solubility parameters estimated by different methods.
Subject(s)
Ionic Liquids/chemistry , Solubility , Thermodynamics , Viscosity , VolatilizationABSTRACT
BACKGROUND AND PURPOSE: Leptomeningeal metastases (LMs) carry a poor prognosis. Existing LM scoring systems show limited reproducibility. We assessed the contribution of education level on the reproducibility of LM scoring using structured planning and implementation of new experiments (SPINE), a novel web-based platform. METHODS: Stringent radiological definitions of LM and a customized interactive scoring system were implemented in SPINE. Five patients with brain LM and 3 patients with spine, but no brain LM, were selected. Each patient's baseline post-contrast T1-weighted brain MRI was analyzed by three attending neuroradiologists, two neuroradiology fellows, and two radiology residents. Raters identified and characterized all LMs based on: (1) location (cerebrum, cerebellum, brainstem, ventricle, and/or cranial nerves); (2) shape (nodular and/or linear/curvilinear); (3) size (≥ or <5mm in two orthogonal diameters); (4) spatial extension (focal or diffuse). Inter-rater agreement and association of LM with patient survival were investigated. RESULTS: On average, 6.5 LMs per case were detected. Forty-nine percent of LMs were cerebral, 77.7% were nodular, 86.6% were focal, and 66% were <5 × 5 mm. Agreement on the total number of LMs and the above-mentioned common LM characteristics was higher between attendings (intra-class correlation [ICC] = 0.8-0.94) than fellows (ICC = 0.6-0.82) or residents (ICC = 0.43-0.73). Agreement on ventricular, cranial nerve, and nodular + linear LM was low even between attendings. The number of brainstem LMs showed significant correlation with survival. CONCLUSION: Structured education using SPINE may improve consistency in LM reporting. Future work should address the impact of the presented approach on the reproducibility of longitudinal analyses directly relevant to the assessment of treatment-response.
Subject(s)
Internet , Meningeal Neoplasms/diagnosis , Meningeal Neoplasms/secondary , Adult , Humans , Intersectoral Collaboration , Magnetic Resonance Imaging , Male , Neuroimaging , Reproducibility of ResultsABSTRACT
The Hildebrand's solubility parameters have been calculated for 18 ionic liquids from the inverse gas chromatography measurements of the activity coefficients at infinite dilution. Retention data were used for the calculation. The solubility parameters are helpful for the prediction of the solubility in the binary solvent mixtures. From the solubility parameters, the standard enthalpies of vaporization of ionic liquids were estimated.
Subject(s)
Ionic Liquids/chemistry , Models, ChemicalABSTRACT
The activity coefficients at infinite dilution, gamma 13 (infinity) for 32 solutes: alkanes, alkenes, alkynes, cycloalkanes, aromatic hydrocarbons, alcohols, thiophene, tetrahydrofurane, tert-butyl methyl ether, and water in the ionic liquid 1-butyl-3-methylimidazolium trifluoromethanesulfonate [BMIM][CF3SO3] were determined by gas-liquid chromatography at the temperatures from 298.15 to 368.15 K. The partial molar excess enthalpies at infinite dilution values Delta H 1 (E,infinity) were calculated from the experimental gamma 13 (infinity) values obtained over the temperature range. The selectivities for the hexane/benzene, cyclohexane/benzene, n-hexane/thiophene, n-decane/thiophene, cyclohexane/thiophene, toluene/thiophene, and oct-1-ene/thiophene separation problems were calculated from the gamma 13 (infinity). Obtained values were compared to the literature values for the other ionic liquids, NMP, and sulfolane.
ABSTRACT
Novel quaternary ammonium ionic liquid, ethyl(2-hydroxyethyl)dimethylammonium bis(trifluomethylsulfonyl)imide (C2NTf2), has been prepared from N,N-dimethylethanolamine as a substrate. The paper includes a specific basic characterization of the synthesized compound by NMR and the basic thermophysical properties: the melting point, enthalpy of fusion, enthalpy of solid-solid phase transition, glass transition determined by the differential scanning calorimetry (DSC), temperature of decomposition, and water content. The density of the new compound was measured. The solid-liquid or liquid-liquid phase equilibria of binary mixtures containing {C2NTf2+water or an alcohol (propan-1-ol, butan-1-ol, hexan-1-ol, octan-1-ol, decan-1-ol), aromatic hydrocarbons (benzene, toluene), aliphatic hydrocarbons (n-hexane, n-octane), dimethylsulfoxide (DMSO), or tetrahydrofuran (THF)} have been measured by a dynamic method in a wide range of temperatures from 230 to 430 K. These data were correlated by means of the nonrandom two-liquid (NRTL) equation utilizing temperature-dependent parameters derived from the solid-liquid or liquid-liquid equilibrium. From the solubility results, the negative value of the partition coefficient of ionic liquid in binary system octan-1-ol/water (log P) at 298.15 K has been calculated.
ABSTRACT
The activity coefficients at infinite dilution, gamma13(infinity) for 29 solutes, alkanes, alkenes, alkynes, cycloalkanes, aromatic hydrocarbons, alcohols and water in the ionic liquid 1-ethyl-3-methylimidazolium trifluoroacetate ([EMIM][TFA]), were determined by gas-liquid chromatography at temperatures from 298.15-368.15 K. The partial molar excess enthalpies at infinite dilution DeltaH1(E,infinity) values were calculated from the experimental gamma13(infinity) values obtained over the temperature range. The selectivities for the hexane/benzene and cyclohexane/benzene separation were calculated from gamma13(infinity) and compared to the literature values for other ionic liquids, NMP and sulfolane.
ABSTRACT
The objective of this work was to evaluate the relationship between chemical reactivity of 3-substituted pyridinium salts and their cytotoxic properties against murine leukemia L1210. Chemical reactivity of pyridinium salts towards NADH oxidation following one-step hydride transfer depends strongly on their redox properties. The investigated reaction may reflect the ability of the salts to deplete NADH level in cells and to affect their metabolic functions. On the other hand, the cytotoxic activity against murine leukemia cells, expressed as ED50 values, varied strongly depending upon the compound used. The investigated salts showed also a diverse antileukemic effect in in vivo experiments as measured by the increase in the survival time of L1210 leukemia-bearing mice. These biological effects were correlated with equilibrium constants found for the reaction of pyridinium salts with NADH.
Subject(s)
Antineoplastic Agents/pharmacology , Leukemia L1210/drug therapy , Pyridines/pharmacology , Animals , Hydrogen-Ion Concentration , Leukemia L1210/pathology , Mice , NAD/chemistry , Oxidation-Reduction , Pyridines/chemistry , Structure-Activity RelationshipABSTRACT
We examined the mechanism through which leptin increases Na(+), K(+)-ATPase activity in the rat kidney. Leptin was infused under anaesthesia into the abdominal aorta proximally to the renal arteries and then Na(+), K(+)-ATPase activity was measured in the renal cortex and medulla. Leptin (1mug/kgmin) increased Na(+), K(+)-ATPase activity after 3h of infusion, which was accompanied by the increase in urinary H(2)O(2) excretion and phosphorylation level of extracellular signal regulated kinase (ERK). The effect of leptin on ERK and Na(+), K(+)-ATPase was abolished by catalase, specific inhibitors of epidermal growth factor (EGF) receptor, AG1478 and PD158780, as well as by ERK inhibitor, PD98059, and was mimicked by both exogenous H(2)O(2) and EGF. The effect of leptin was also prevented by the inhibitor of Src tyrosine kinase, PP2. Leptin and H(2)O(2) increased Src phosphorylation at Tyr(418). We conclude that leptin-induced stimulation of renal Na(+), K(+)-ATPase involves H(2)O(2) generation, Src kinase, transactivation of the EGF receptor, and stimulation of ERK.
Subject(s)
ErbB Receptors/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Hydrogen Peroxide/metabolism , Kidney/enzymology , Leptin/physiology , Sodium-Potassium-Exchanging ATPase/metabolism , src-Family Kinases/physiology , Animals , Rats , Rats, WistarABSTRACT
BACKGROUND: Abnormal neurohormonal regulation of renal sodium handling plays an important role in obesity-associated hypertension. We investigated the effect of experimental obesity on renal response to atrial natriuretic peptide (ANP). METHODS: The effect of ANP was studied in three groups of rats: (1) lean controls, (2) animals made obese by a highly palatable diet, (3) rats treated with adipose tissue hormone, leptin, for 7 days to reproduce hyperleptinemia observed in obesity. RESULTS: ANP administered at a dose of 50 pmol/kg min(-1) induced about a 3-fold lower increase in Na+ and cGMP excretion in obese and leptin-treated rats than in the control group. ANP decreased Na+,K+-ATPase activity in the renal medulla only in the control group. Natriuretic effect of exogenous cGMP was also impaired in obese and leptin-treated rats. In contrast, hydrolysis-resistant cGMP derivative, 8-bromo-cGMP exerted comparable natriuretic effects in all groups. Neutral endopeptidase inhibitor, phosphoramidon, and ANP clearance receptor antagonist, C-ANP, increased urinary ANP excretion in all groups to a similar level, but their natriuretic effect was impaired in obese and leptin-treated groups. A specific inhibitor of cGMP-degrading phosphodiesterase, zaprinast, had comparable natriuretic and Na+,K+-ATPase-lowering effects in all groups and restored normal sensitivity to ANP. CONCLUSIONS: (1) Dietary-induced obesity is accompanied by impaired natriuretic effect of ANP, (2) ANP resistance in obesity may be accounted for by increased leptin level, (3) accelerated degradation of cGMP may contribute to ANP resistance associated with obesity and hyperleptinemia, suggesting that inhibiting cGMP-specific phosphodiesterases may be useful in the treatment of obesity-associated hypertension.
Subject(s)
Atrial Natriuretic Factor/pharmacology , Drug Resistance/drug effects , Hyperlipidemias/physiopathology , Kidney/drug effects , Kidney/metabolism , Obesity/physiopathology , Phosphodiesterase Inhibitors/pharmacology , Phosphoric Diester Hydrolases/metabolism , 3',5'-Cyclic-GMP Phosphodiesterases , Animals , Atrial Natriuretic Factor/urine , Cyclic GMP/urine , Cyclic Nucleotide Phosphodiesterases, Type 5 , Hyperlipidemias/chemically induced , Hyperlipidemias/complications , Male , Obesity/complications , Rats , Rats, Wistar , Sodium/metabolismABSTRACT
AIM: To analyze the major complications after exenteration of gynecological and rectal malignancies. METHODS: Twenty-two patients with gynecological malignancy and 6 with rectal malignancy underwent pelvic exenteration (PE) between 1996 and 2005. PE was performed for primary malignancy in 71.4% of cases (vulvar cancer in 13, cancer rectal in 5, cervical cancer in 1 and Bartholin's gland cancer in 1 cases respectively and recurrent malignancy in 28.6% of cases (cervical cancer in 5, ovarian cancer in 1, uterine sarcoma in 1 and rectal cancer in 1 cases respectively). Posterior PE, total PE and anterior PE were most often performed. RESULTS: Major complications in the operative field involving the urinary tract infection or the wound dehiscence occurred in 12 patients (42.9%). Early complications included massive bleeding from the sacral plexus, adult respiratory distress syndrome (ARDS), thrombophlebitis, acute renal failure, urinary bladder dysfunction, ureter damage, re-operation and pulmonary embolus. Urinary incontinence was observed in 2 women as a late complication. In 1 patient a nephrostomy was performed in 1 patient due to extensive hydronephrosis and 1 patient had complications connected with the gastrointestinal tract. The mortality rate was 7%, of which inter-operative mortality accounted for 3.5%. Major complications often occurred in advanced primary vulvar cancer affecting those with recurrent malignancies. CONCLUSION: PE is more beneficial to patients with primary vulvar and rectal cancer than to those with recurrent cancer. Knowledge of the inherent complications and morbidity of PE is essential.
Subject(s)
Genital Neoplasms, Female/surgery , Pelvic Exenteration/adverse effects , Pelvic Neoplasms/surgery , Postoperative Complications/etiology , Rectal Neoplasms/surgery , Surgical Wound Dehiscence/etiology , Acute Kidney Injury/etiology , Adult , Aged , Aged, 80 and over , Female , Humans , Longitudinal Studies , Middle Aged , Neoplasm Recurrence, Local/etiology , Pelvic Exenteration/methods , Pelvic Exenteration/mortality , Postoperative Hemorrhage/etiology , Respiratory Distress Syndrome/etiology , Retrospective Studies , Time Factors , Treatment Outcome , Urinary Tract Infections/etiologyABSTRACT
This is a report of two cases of haemorrhage after pelvic exenteration in patients with vulvar cancer and cervical cancer treated by temporary pelvic packing at the Department of Gynaecology of the Medical University in Gdansk. The packing was successful and the sponges were removed after 24 and 48 hours. There were no major postoperative complications in both cases and one wound dehiscence. Both patients recovered after surgery. In cases with severe intraoperative haemorrhage, intraabdominal packing can be effective mode of treatment, especially in bleeding which originates from the sacral venous plexus.
Subject(s)
Blood Loss, Surgical/prevention & control , Pelvic Exenteration/methods , Uterine Cervical Neoplasms/surgery , Vulvar Neoplasms/surgery , Female , Humans , Intraoperative Complications/prevention & control , Middle Aged , Surgical Sponges , Treatment Outcome , Uterine Cervical Neoplasms/pathology , Vulvar Neoplasms/pathologyABSTRACT
To date, it remains unclear whether mild form of acute pancreatitis (AP) may cause myocardial damage which may be asymptomatic for a long time. Pathogenesis of AP-related cardiac injury may be attributed in part to ROS/RNS overproduction. The aim of the present study was to evaluate the oxidative stress changes in both the pancreas and the heart and to estimate the protective effects of 1-oxyl-2,2,6,6-tetramethyl-4-hydroxypiperidine (tempol) at the early phase of AP. Cerulein-induced AP led to the development of acute edematous pancreatitis with a significant decrease in the level of sulfhydryl (-SH) groups (oxidation marker) both in heart and in pancreatic tissues as well as a substantial increase in plasma creatine kinase isoenzyme (CK-MB) activity (marker of the heart muscle lesion) which confirmed the role of oxidative stress in the pathogenesis of cardiac damage. The tempol treatment significantly reduced the intensity of inflammation and oxidative damage and decreased the morphological evidence of pancreas injury at early AP stages. Moreover, it markedly attenuated AP-induced cardiac damage revealed by normalization of the -SH group levels and CK-MB activity. On the basis of these studies, it is possible to conclude that tempol has a profound protective effect against cardiac and pancreatic damage induced by AP.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Cardiotonic Agents/therapeutic use , Cell Membrane Permeability/drug effects , Cyclic N-Oxides/therapeutic use , Free Radical Scavengers/therapeutic use , Pancreatitis/chemically induced , Pancreatitis/drug therapy , Amylases/blood , Animals , Anti-Inflammatory Agents/pharmacology , Antioxidants/metabolism , Cardiotonic Agents/pharmacology , Ceruletide , Creatine Kinase, MB Form/blood , Cyclic N-Oxides/administration & dosage , Cyclic N-Oxides/pharmacology , Disease Models, Animal , Free Radical Scavengers/pharmacology , Male , Oxidative Stress/drug effects , Pancreas/drug effects , Pancreas/pathology , Pancreatitis/blood , Pancreatitis/enzymology , Rats, Wistar , Spin Labels , Water/metabolismABSTRACT
Leptin, secreted by adipose tissue, is involved in the pathogenesis of arterial hypertension, however, the mechanisms through which leptin increases blood pressure are incompletely elucidated. We investigated the effect of leptin, administered for different time periods, on renal Na(+),K(+)-ATPase activity in the rat. Leptin was infused under anesthesia into the abdominal aorta proximally to the renal arteries for 0.5-3 h. Leptin administered at doses of 1 and 10 microg/min per kg for 30 min decreased the Na(+),K(+)-ATPase activity in the renal medulla. This effect disappeared when the hormone was infused for > or =1 h. Leptin infused for 3 h increased the Na(+),K(+)-ATPase activity in the renal cortex and medulla. The stimulatory effect was abolished by a specific inhibitor of Janus kinases (JAKs), tyrphostin AG490, as well as by an NAD(P)H oxidase inhibitor, apocynin. Leptin increased urinary excretion of hydrogen peroxide (H(2)O(2)) between 2 and 3 h of infusion. The effect of leptin on renal Na(+),K(+)-ATPase and urinary H(2)O(2) was augmented by a superoxide dismutase mimetic, tempol, and was abolished by catalase. In addition, infusion of H(2)O(2) for 30 min increased the Na(+),K(+)-ATPase activity. Inhibitors of extracellular signal regulated kinases (ERKs), PD98059 or U0126, prevented Na(+),K(+)-ATPase stimulation by leptin and H(2)O(2). These data indicate that leptin, by acting directly within the kidney, has a delayed stimulatory effect on Na(+),K(+)-ATPase, mediated by JAKs, H(2)O(2) and ERKs. This mechanism may contribute to the abnormal renal Na(+) handling in diseases associated with chronic hyperleptinemia such as diabetes and obesity.
Subject(s)
Kidney Cortex/enzymology , Kidney/enzymology , Leptin/pharmacology , Sodium-Potassium-Exchanging ATPase/metabolism , Animals , Iron/metabolism , Kinetics , Oxidation-Reduction , Protein-Tyrosine Kinases/metabolism , Rats , Rats, Wistar , Sodium-Potassium-Exchanging ATPase/drug effectsABSTRACT
Recent studies suggest that adipose tissue hormone, leptin, is involved in the pathogenesis of arterial hypertension. However, the mechanism of hypertensive effect of leptin is incompletely understood. We investigated whether antioxidant treatment could prevent leptin-induced hypertension. Hyperleptinemia was induced in male Wistar rats by administration of exogenous leptin (0.25 mg/kg twice daily s.c. for 7 days) and separate groups were simultaneously treated with superoxide scavenger, tempol, or NAD(P)H oxidase inhibitor, apocynin (2 mM in the drinking water). After 7 days, systolic blood pressure was 20.6% higher in leptin-treated than in control animals. Both tempol and apocynin prevented leptin-induced increase in blood pressure. Plasma concentration and urinary excretion of 8-isoprostanes increased in leptin-treated rats by 66.9% and 67.7%, respectively. The level of lipid peroxidation products, malonyldialdehyde + 4-hydroxyalkenals (MDA+4-HNE), was 60.3% higher in the renal cortex and 48.1% higher in the renal medulla of leptin-treated animals. Aconitase activity decreased in these regions of the kidney following leptin administration by 44.8% and 45.1%, respectively. Leptin increased nitrotyrosine concentration in plasma and renal tissue. Urinary excretion of nitric oxide metabolites (NO(x)) was 57.4% lower and cyclic GMP excretion was 32.0% lower in leptin-treated than in control group. Leptin decreased absolute and fractional sodium excretion by 44.5% and 44.7%, respectively. Co-treatment with either tempol or apocynin normalized 8-isoprostanes, MDA+4-HNE, aconitase activity, nitrotyrosine, as well as urinary excretion of NO(x), cGMP and sodium in rats receiving leptin. These results indicate that oxidative stress-induced NO deficiency is involved in the pathogenesis of leptin-induced hypertension.
Subject(s)
Antioxidants/pharmacology , Blood Pressure/drug effects , Kidney/metabolism , Leptin/blood , Natriuresis/drug effects , Nitric Oxide/metabolism , Acetophenones/pharmacology , Aconitate Hydratase/metabolism , Aldehydes/metabolism , Animals , Body Weight/drug effects , Creatine/metabolism , Cyclic GMP/blood , Cyclic GMP/urine , Cyclic N-Oxides/pharmacology , Drinking/drug effects , Eating/drug effects , Hypertension/blood , Hypertension/physiopathology , Isoprostanes/blood , Isoprostanes/urine , Kidney/drug effects , Male , Malondialdehyde/metabolism , Rats , Rats, Wistar , Reactive Nitrogen Species/blood , Reactive Nitrogen Species/urine , Sodium/metabolism , Sodium/urine , Spin Labels , Tyrosine/analogs & derivatives , Tyrosine/blood , Tyrosine/metabolismABSTRACT
Hyperleptinemia may be involved in the pathogenesis of obesity-associated hypertension, however, the mechanism of hypertensive effect of leptin is incompletely elucidated. Previously, we have demonstrated that chronic hyperleptinemia causes up-regulation of renal Na+,K+-ATPase and decreases urinary Na+ excretion. Herein, we investigated whether antioxidant treatment could correct these abnormalities. The study was performed on male Wistar rats. Leptin administered for 7 days (0.25 mg/kg twice daily sc) increased systolic blood pressure by 20.6%. Leptin had no effect on urine output and creatinine clearance but reduced sodium excretion by 40.1%. Na+,K+-ATPase activity in the renal cortex and medulla was higher in leptin-treated rats by 24.3% and 80.6%, respectively. In addition, hyperleptinemia was associated with an increase in plasma and urinary 8-isoprostanes and reduced urinary excretion of nitric oxide (NO) metabolites and cGMP. Co-treatment with a superoxide dismutase mimetic, tempol, or an NAD(P)H oxidase inhibitor, apocynin (2 mM in the drinking water), prevented leptin-induced blood pressure elevation, normalized plasma and urinary 8-isoprostanes, urinary excretion of sodium, NO metabolites and cGMP, as well as prevented up-regulation of renal Na+,K+-ATPase activity. These data suggest that hyperleptinemia increases renal Na+,K+-ATPase activity and reduces natriuresis by inducing oxidative stress-dependent NO deficiency. Antioxidant treatment is effective in leptin-induced hypertension and should be considered in controlling blood pressure in hyperleptinemic obese individuals.
Subject(s)
Antioxidants/pharmacology , Kidney/drug effects , Leptin/blood , Sodium-Potassium-Exchanging ATPase/metabolism , Animals , Blood Pressure/drug effects , Creatinine/blood , Creatinine/urine , Kidney/enzymology , Kidney Function Tests , Leptin/pharmacology , Male , Nitric Oxide/metabolism , Rats , Rats, WistarABSTRACT
OBJECTIVES: The pelvic exenteration is a method of treatment in cases of recurrence or locally advanced gynecological tumors without distance metastases. The total pelvic exenteration has been used as salvage therapy especially for advanced gynecological malignancy. DESIGN: The aim of study was to analyse the group of women who underwent pelvic exenteration. MATERIAL AND METHODS: A series of 13 patients who underwent pelvic exenteration for advanced vulvar cancer at the Department of Gynecology, Medical University of Gdansk Poland between 1996-2003 was retrospectively reviewed. RESULTS: The more often performed exenteration in patients with vulvar cancer was posterior pelvic exenteration in 11 cases, total pelvic exenteration in 2 cases. The mean age at diagnosis was 56 years. The estimated blood transfusion due to operation ranged from 300 ml to 3580 ml with a mean of 1200 ml. The operating time ranged from 4 hours to 7 hours 30 minutes with a mean of 6 hours and 5 minutes. Patients stayed in hospital from 14 to 54 days after operation with a mean 33 days. The overall complication rate after pelvic exenteration was 61.5% with 8 of the 13 patients. Three times it was infection, six times wound dehiscence, in 1 case it was: ARDS, thrombophlebitis, ureter damage. There was no late complication. CONCLUSION: Pelvic exenteration offers the last chance for some women with gynecological malignancy.