ABSTRACT
The aviation industry generates a significant amount of comingle waste. Nowadays, companies are making efforts to enhance waste management and reduce waste generation. In order to improve present practices and implement a proper waste management system, the quantities, materials, and typology of waste generated need to be studied. A total of 145 airplanes were analysed. We differentiated 5 strips of duration and identified 4 different generation sources within the cabin associated to the business and tourist passenger classes. We classified and characterized the waste into 20 different materials. Results provide a detailed, representative and adapted study of the catering waste generated in the aviation industry. The characterization, which allows distinguishing between manipulated and unmanipulated materials, aims at providing useful information to reduce the generation of waste. The analysis performed in the present study shows that the flying distance increases the waste generation, as more food is served. It also shows that organic matter, paper/cardboard and packaging are the dominant materials in the waste generated in flights. The results of the characterizations obtained allow making some recommendations. The use of bi-compartmentalized waste trolleys to separate on-board recyclable materials from the rest is desirable to obtain a clean recoverable waste stream. Supressing unpopular food from menus, identified analysing the leftovers, could also reduce the amount of waste generated. (This characterization study is part of the European project LIFEâ¯+â¯Zero Cabin Waste.). Changes in the CE 1069/2009 regulation would allow more waste to be recycled instead of landfilled. Ultimately, the information obtained from this study will be used to design a more sustainable waste management system.
Subject(s)
Waste Management , Aircraft , Food , Product Packaging , RecyclingABSTRACT
The melanocortin 1 receptor (MC1R) gene was investigated as a candidate for plumage variations in Chinese painted quail, Coturnix chinensis. Four silent and two missense nucleotide polymorphisms were identified. The correspondent amino acid changes, p.Glu92Lys and p.Pro292Leu, were found in Blue Face and Red Breasted animals respectively. Blue Face is a melanic phenotype similar to the co-dominant Extended Brown of Japanese quail, and both share the p.Glu92Lys mutation. The association of p.Pro292Leu with the recessive Red Breasted was confirmed in 23 animals from an experimental F2 cross.
Subject(s)
Avian Proteins/genetics , Coturnix/anatomy & histology , Coturnix/genetics , Mutation, Missense , Receptor, Melanocortin, Type 1/genetics , Silent Mutation , Animals , Coturnix/classification , Feathers/anatomy & histology , Female , Male , Pigmentation , Polymorphism, GeneticABSTRACT
PurposeTo develop and validate a Bayesian belief network algorithm for the differential diagnosis of anterior uveitis.Patients and methodsThe 11 most common etiologies were included (idiopathic, ankylosing spondylitis, psoriasic arthritis, reactive arthritis, inflammatory bowel diseases, sarcoidosis, tuberculosis, Behçet, Posner-Schlossman syndrome, juvenile idiopathic arthritis (JIA), and Fuchs' heterochromic cyclitis). Frequencies of association between factors and etiologies were retrieved from a systematic review of the literature. Prevalences were calculated using a random sample of 200 patients receiving a diagnosis of anterior uveitis in Moorfields Eye Hospital in 2012. The network was validated in a random sample of 200 patients receiving a diagnosis of anterior uveitis in the same hospital in 2013 plus 10 extra cases of the most rare etiologies (JIA, Behçet, and psoriasic arthritis).ResultsIn 63.8% of patients the most probable etiology by the algorithm matched the senior clinician diagnosis. In 80.5% of patients the clinician diagnosis matched the first or second most probable results by the algorithm. Taking into account only the most probable diagnosis by the algorithm, sensitivities for each etiology ranged from 100% (7 of 7 patients with reactive arthritis and 5 of 5 with Behçet correctly classified) to 46.7% (7 of 15 patients with tuberculosis-related uveitis). Specificities ranged from 88.8% for sarcoidosis to 99.5% in Posner.ConclusionsThis algorithm could help clinicians with the differential diagnosis of anterior uveitis. In addition, it could help with the selection of the diagnostic tests performed.
Subject(s)
Algorithms , Bayes Theorem , Uveitis, Anterior/diagnosis , Diagnosis, Differential , Humans , Prevalence , Sensitivity and SpecificityABSTRACT
BACKGROUND: Maternal nutrition is the main source of Poly-Unsaturated Fatty Acids (PUFA) for the fetus. PUFA may influence the accumulation of fat in early life. OBJECTIVES & METHODS: In 33 breastfed infants born appropriate-for-gestational-age, we studied whether body composition (judged by absorptiometry at 2 wk and 4 mo) relates to PUFA levels (assessed by gas chromatography) in the maternal or fetal circulation at birth. RESULTS: Abdominal fat at 2 wk associated negatively to umbilical-cord levels of separate PUFA (linoleic, arachidonic, eicosapentanoic and docosahexaenoic acid; all P between 0.001 and 0.015). Collectively, the assessed n-6â PUFA on one hand and the n-3â PUFA on the other hand associated negatively to the absolute amount of abdominal fat (in grams; P = 0.001 and P = 0.002, respectively) and to the relative amount of abdominal fat (fraction of total fat; P = 0.001 and P = 0.006, respectively). No other significant associations were observed. CONCLUSION: In conclusion, newborns with lower levels of circulating PUFA were found to be abdominally more adipose. The mechanisms underpinning these associations remain to be determined.
Subject(s)
Adiposity , Fatty Acids, Unsaturated/metabolism , Mothers , Obesity, Abdominal/blood , Prenatal Exposure Delayed Effects/blood , Adult , Body Composition , Breast Feeding , Dietary Supplements , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Maternal Nutritional Physiological Phenomena , Pregnancy , Prenatal Nutritional Physiological PhenomenaABSTRACT
We have characterized a deletion in the MC1R gene causing the loss of one amino acid (p.Phe256del), which is perfectly associated with melanism in guinea fowl (Numida meleagris). Co-segregation of the p.Phe256del with melanism was confirmed in 25 offspring born from a cross of two heterozygote birds; therefore we suggest that this mutation is responsible for the black phenotype. Interestingly, this is the first case of recessive melanism linked to MC1R.
Subject(s)
Amino Acid Sequence/genetics , Melanosis/genetics , Phenylalanine/genetics , Receptor, Melanocortin, Type 1/genetics , Sequence Deletion/genetics , Animals , DNA/genetics , DNA/isolation & purification , DNA Primers , Feathers/chemistry , Galliformes/genetics , Genotype , Mutation , Phenotype , Species SpecificityABSTRACT
BACKGROUND: The Directive 2001/20/EC was an important first step towards consistency in the requirements and processes for clinical trials across Europe. However, by applying the same rules to all types of drug trials and transposing the Directive's principles into pre-existing national legislations, the Directive somewhat failed to meet its facilitation and harmonization targets. In the field of ethics, the Directive 2001/20/EC conditioned the way of understanding and transposing the "single opinion" process in each country. This led to a situation in which two models of research ethics committees organisation systems exist, being the model in which the "single opinion" is considered to be the decision made by a single ethics committee more effective and simpler in terms of administrative and logistic workload. METHOD: A survey was conducted in 10 European countries. Members of the European Clinical Research Infrastructures Network working party number 1, with expertise in the field of ethics, responded. RESULTS: There is a major heterogeneity in the composition of ethics committees among the surveyed countries based on the number of members, proportion of experts versus lay members and expertise of the scientific members. A harmonized education of the ethics committees' membership based in common curricula is recommended by the majority of countries. CONCLUSIONS: Despite the efforts for harmonization of the European Clinical Trial Directive, from an ethical point of view, there remains a plurality of ethics committees' systems in Europe. It is important to comprehend the individual national systems to understand the problems they are facing.
Subject(s)
Ethics Committees, Research/organization & administration , Guideline Adherence/ethics , Quality Assurance, Health Care/organization & administration , Clinical Trials as Topic , Conflict of Interest , Ethics Committees, Research/ethics , European Union , Humans , International Cooperation , Quality Assurance, Health Care/ethicsABSTRACT
Low severity of GVHD, substantial graft vs tumor (GVT) and slow development of protective immunity are well-documented features of cord blood transplants (CBT). We have evaluated the immune reconstitution of adult recipients of single-unit CBT supported by the coinfusion of third party donor (TPD) mobilized hematopoietic stem cells (MHSC), a procedure-'dual CB/TPD-MHSC transplant'-that results in early recovery of circulating granulocytes, high rates of CB engraftment and full chimerism. Cumulative recovery of natural killer and B cells at or above the median values of normal controls were 1.0 and 0.76 by the sixth and ninth months. Recovery of T cells was much slower, naive cells lagging behind those of memory and effector (committed) immunophenotypes. Serial analyses of signal joint TCR excision circles showed a general pattern of very low levels by the third month after CBT, followed by recovery to levels persistently similar or higher than those observed before transplantation and in normal controls. Our results are consistent with the clinical observations of substantial GVT effect together with low incidence of serious GVHD and slow development of protective immunity and suggest that thymic function contributes substantially to the recovery of T-cell populations in adults receiving dual CB/TPD-MHSC transplants.
Subject(s)
Cord Blood Stem Cell Transplantation/methods , Hematologic Neoplasms/surgery , Hematopoietic Stem Cell Transplantation/methods , Adult , Disease-Free Survival , Female , Graft Survival/immunology , Graft vs Host Disease/immunology , Hematologic Neoplasms/immunology , Hematopoietic Stem Cell Mobilization , Histocompatibility Testing , Humans , Kaplan-Meier Estimate , Living Donors , Lymphocyte Activation/immunology , Male , Middle Aged , Transplantation Conditioning , Transplantation Immunology , Young AdultABSTRACT
Pulsed infrared light therapy (PILT) has been shown to increase peripheral sensation in diabetic patients with diabetic peripheral neuropathy (DPN). However, most studies last for very short periods, with the subjects receiving only 6-20 treatments. The purpose of this study was to evaluate the effectiveness of an eight-week course of PILT in reversing long-standing, profound DPN in patients with type 1 and type 2 diabetes. Twenty-two subjects with a diagnosis of type 1 (n=2) or type 2 (n=20) diabetes participated in the study. PILT was administered to one foot chosen at random with the other foot serving as a within-subject control (no treatment). Patients underwent 24 treatments (3 times/week, for eight weeks) for 30 min per treatment. Changes in peripheral protective sensation (PPS) were measured using Semmes-Weinstein monofilaments (SWM) ranging from 3.7 to 6.48. PILT improved PPS even in patients with long-standing chronic neuropathies whose initial pre-study sensation was not measurable with a 200-g SWM. PILT significantly improves PPS. While the exact mechanism of action is not understood, infrared light may improve peripheral neuropathies by improving foot perfusion by stimulating nitric oxide production.
Subject(s)
Diabetes Mellitus, Type 1/radiotherapy , Diabetes Mellitus, Type 2/radiotherapy , Diabetic Neuropathies/radiotherapy , Infrared Rays/therapeutic use , Body Mass Index , Body Temperature , Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Glycated Hemoglobin/analysis , Humans , Patient Selection , Peripheral Nervous System Diseases/radiotherapy , Skin Temperature , Spain , WalkingABSTRACT
PURPOSE: To study the clinical signs, treatment and prognosis of strabismus after sub-Tenon's anesthesia for cataract surgery. METHODS: Eight patients without previous strabismus developed incomitant diplopia immediately after cataract surgery; the left eye was affected in five patients and the right eye in three. Restrictive strabismus was diagnosed with the cover test, prisms, and active and passive ductions in all cases. In seven cases the deviation was vertical and in one patient it was horizontal. The average deviation was 17.5 S.D. 9.84 (range 5-35) prismatic dioptres in primary position. The deviation increased looking upward in seven cases, and looking sideways to the left in the other. It was considered to be a good result if the diplopia disappeared after treatment. RESULTS: Botulinum toxin was the first treatment applied in four patients, but only one showed a good response and required no further therapy. Strabismus surgery was required in four cases, and prisms were adapted in three. Three patients required two strabismus operations. A good result was achieved in all cases, with the average time interval being 10.12 (SD 5.5) months. CONCLUSIONS: Sub-Tenon's anesthesia may result in restrictive strabismus and incomitant diplopia which does not resolve spontaneously. The inferior rectus is the most commonly affected muscle. Strabismus surgery is required to resolve the diplopia in half of the cases. Good results have been achieved in all patients.
Subject(s)
Anesthesia, Local/adverse effects , Cataract Extraction/adverse effects , Diplopia/etiology , Strabismus/etiology , Aged , Aged, 80 and over , Anesthesia, Local/methods , Botulinum Toxins, Type A/administration & dosage , Cataract Extraction/methods , Diplopia/drug therapy , Female , Humans , Male , Neuromuscular Agents/administration & dosage , Postoperative Complications , Strabismus/drug therapy , Treatment Outcome , Visual AcuityABSTRACT
UNLABELLED: The incidence of empyema thoracis in children seems to be increasing. The objective [corrected] of this study is to propose a rational initial treatment of parapneumonic effusions in order to reduce hospital stay and late-stage empyema complications. Medical records of 33 children presenting parapneumonic effusions who required any surgical therapy between 1997 and 2002 were reviewed. They were grouped as (I) successful management with chest tube, (II) successful management with intrapleural instillation of urokinase and (III) successful surgical treatment: (IIIa) thoracoscopy or (IIIb) thoracotomy. CONCLUSION: Early sonographic evaluation of parapneumonic effusions is usefull to evaluate the severity of disease and the need for surgical intervention. Thoracoscopic-assisted surgery is an effective treatment for pediatric early-stage empyema. Thoracotomy is indicated for most children with established empyema.
Subject(s)
Pleural Effusion/complications , Pneumonia/complications , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Pleural Effusion/diagnostic imaging , Pneumonia/diagnostic imaging , Radiography, Thoracic , UltrasonographyABSTRACT
AIM: To compare the anatomical and functional success of primary scleral buckling, performed either alone or in combination with vitrectomy, for primary retinal detachment (RD) in phakic eyes and in eyes had undergone uneventful phacoemulsification and had received posterior chamber lens implantations. METHODS: A total of 243 consecutive patients were included in this retrospective, nonrandomized comparative study. In all, 165 phakic and 78 pseudophakic individuals with primary RD underwent scleral buckling alone or in combination with vitrectomy and were followed up for 6 months. Pre-, intra- and postoperative findings including anatomical success, best-corrected visual acuity (BCVA), complications, and the development of proliferative vitreoretinopathy (PVR), macular pucker, or secondary cataracts were recorded. Cases requiring more than one surgical intervention were defined having failed, although further surgical intervention might have led to success. RESULTS: At 6 months after scleral buckling alone, the anatomical success was similar in phakic (88.98%) and pseudophakic (87.65%) eyes (log rank=0.310). The corresponding results after scleral buckling with vitrectomy were 82.13 and 77.63% for phakic and pseudophakic eyes, respectively (log rank=0.799). At 6 months after scleral buckling alone, BCVA was similar in phakic and pseudophakic eyes (0.62+/-0.30 vs 0.70+/-0.29; P=0.227). Likewise, after scleral buckling with vitrectomy, BCVA did not differ significantly (P=0.322) between phakic (0.34+/-0.32) and pseudophakic eyes (0.50+/-0.27). CONCLUSION: The anatomical and functional outcome of primary retinal reattachment surgery, involving scleral buckling alone or in combination with vitrectomy, is similar in phakic and pseudophakic eyes.
Subject(s)
Aphakia, Postcataract/complications , Pseudophakia/complications , Retinal Detachment/surgery , Scleral Buckling , Vitrectomy , Adult , Aged , Female , Humans , Male , Middle Aged , Retinal Detachment/complications , Retinal Detachment/pathology , Retrospective Studies , Scleral Buckling/adverse effects , Treatment Outcome , Visual Acuity , Vitrectomy/adverse effectsABSTRACT
Hemodynamic care during postoperative management of myocardial revascularization should include vasorelaxing drugs to insure adequate graft and coronary flow, and stimulation of stroke volume to maintain vascular perfusion pressure. We tested the cardiac (inotropic and lusitropic) and vascular (relaxant) effects of diltiazem (0.1 nM to 0.1 mM), dobutamine (10 microM to 10 mM) and amrinone (10 microM to 1 mM) on isolated rat atria and thoracic aorta, and also on isolated human saphenous vein (HSV) and human mammary artery (HMA). Dobutamine produced a maximal positive inotropic effect (+dF/dt max = 29 +/- 7%) at its ED50 for aortic relaxation (88 +/- 7 microM). Conversely, at their ED50 for aortic relaxation diltiazem depressed myocardial contractility and amrinone did not exhibit myocardial effects. In HSV and HMA contracted with 80 mM potassium, diltiazem and dobutamine (but not amrinone) had a vasorelaxant activity similar to that in rat aorta. Norepinephrine-contracted human vessels were significantly more sensitive than potassium-contracted vessels to the relaxant effect of amrinone (ED50 HMA = 15 +/- 5 microM, ED50 HSV = 72 +/- 31 microM, P < 0.05). We conclude that at concentrations still devoid of myocardial effects dobutamine and amrinone are effective dilators in graft segment vessels and rat aorta contracted by membrane depolarization. If the difference between aortic and myocardial tissue still holds in human tissues, at the appropriate concentrations these drugs should be expected to improve cardiac performance while still contributing to the maintenance of graft patency.
Subject(s)
Amrinone/pharmacology , Cardiotonic Agents/pharmacology , Diltiazem/pharmacology , Dobutamine/pharmacology , Myocardial Revascularization , Vasodilator Agents/pharmacology , Animals , Aorta/drug effects , Aorta/physiology , Female , Heart Atria/drug effects , Humans , Male , Mammary Arteries/drug effects , Mammary Arteries/physiology , Rats , Rats, Sprague-Dawley , Saphenous Vein/drug effects , Saphenous Vein/physiologyABSTRACT
Hemodynamic care during postoperative management of myocardial revascularization should include vasorelaxing drugs to insure adequate graft and coronary flow, and stimulation of stroke volume to maintain vascular perfusion pressure. We tested the cardiac (inotropic and lusitropic) and vascular (relaxant) effects of diltiazem (0.1 nM to 0.1 mM), dobutamine (10 æM to 10 mM) and amrinone (10 æM to 1 mM) on isolated rat atria and thoracic aorta, and also on isolated human saphenous vein (HSV) and human mammary artery (HMA). Dobutamine produced a maximal positive inotropic effect (+dF/dt max = 29 ñ 7 percent) at its ED50 for aortic relaxation (88 ñ 7 æM). Conversely, at their ED50 for aortic relaxation diltiazem depressed myocardial contractility and amrinone did not exhibit myocardial effects. In HSV and HMA contracted with 80 mM potassium, diltiazem and dobutamine (but not amrinone) had a vasorelaxant activity similar to that in rat aorta. Norepinephrine-contracted human vessels were significantly more sensitive than potassium-contracted vessels to the relaxant effect of amrinone (ED50 HMA = 15 ñ 5 æM, ED50 HSV = 72 ñ 31 æM, P < 0.05). We conclude that at concentrations still devoid of myocardial effects dobutamine and amrinone are effective dilators in graft segment vessels and rat aorta contracted by membrane depolarization. If the difference between aortic and myocardial tissue still holds in human tissues, at the appropriate concentrations these drugs should be expected to improve cardiac performance while still contributing to the maintenance of graft patency.
Subject(s)
Animals , Male , Female , Rats , Aorta , Cardiotonic Agents , Heart Atria , Myocardial Revascularization , Vasodilator Agents , Amrinone , Diltiazem , Dobutamine , Rats, Sprague-DawleyABSTRACT
The annealing behavior of twice-folded crystals of the long-chain alkane C294H590 is examined in situ, in real time, by atomic force microscopy (AFM). AFM is capable of following processes in real time provided that the time scale is sufficiently long for several images to be collected during the process. In this paper, we focus on the temperature dependence and the thickened morphology. We are able to investigate where the thickening starts and how this depends on temperature and how melting is influenced by morphology. By following the motion of holes within the crystal, a lower limit for the rate of diffusion of crystalline polyethylene is estimated. We also focus on the substrate effect on the crystal morphology and thickening, using mica, glass, and graphite.
ABSTRACT
BACKGROUND/PURPOSE: Significant oesophageal eosinophilia is associated with oesophagitis and gastroesophageal reflux (GER). Eosinophilic oesophagitis is a rare disease that causes thickening of the oesophageal wall, narrowing of the oesophageal lumen, and severe motor disturbance. METHODS AND RESULTS: Two 12 yr-old patients with eosinophilic oesophagitis were studied prospectively. Clinical and investigation details are presented. Elemental formula was administered until complete remission of disease. Final outcome was assessed after 3 months on regular diet with exclusion of specific allergic components. Both patients responded to the dietary manipulation. CONCLUSIONS: Eosinophilic oesophagitis must be included in the differential diagnosis when dealing with oesophageal strictures of unknown or unclear aetiology. Elimination diet therapy plays a crucial role in ameliorating the course of the illness. Blood eosinophilia correlates with therapeutic response and with improvement of the disease.
Subject(s)
Eosinophilia/diet therapy , Esophageal Stenosis/diet therapy , Esophagitis/diet therapy , Food, Formulated , Barium Sulfate , Child , Diagnosis, Differential , Eosinophilia/diagnosis , Eosinophilia/pathology , Esophageal Stenosis/diagnosis , Esophageal Stenosis/diagnostic imaging , Esophagitis/diagnostic imaging , Esophagitis/pathology , Esophagus/diagnostic imaging , Esophagus/pathology , Esophagus/physiology , Humans , Male , Prospective Studies , Radiography , Treatment OutcomeABSTRACT
The human saphenous vein (HSV) is currently used as a graft in coronary revascularization as well as in some other vascular beds, namely those of the inferior limbs. Since a significant proportion of HSV grafts develop stenosis, many studies have focused on the factors that could promote graft failure. This article reviews the results on structural and functional features that might be concurrent in the production of saphenous vein graft stenosis. The reactivity of HSV to several physiological agonists is analyzed, including those derived from the endothelium with contractile or relaxing properties, since these are relevant inducers of graft spasm and/or modifiers of the expression of graft factors involved in either tissue growth or thrombotic-atherosclerotic processes. Mechanisms that regulate vascular smooth muscle contractile state, in particular the activity of K+ channels of the plasma membrane, are described.
Subject(s)
Coronary Artery Bypass/methods , Saphenous Vein/transplantation , Humans , Muscle Contraction/physiology , Muscle, Smooth, Vascular/physiology , Potassium Channels/physiology , Saphenous Vein/anatomy & histology , Saphenous Vein/physiologyABSTRACT
BACKGROUND: In 1998, arsenic concentrations of more than 50 micrograms/l were detected in some drinking water supplies from underground sources in the Autonomous Community of Madrid, which is the maximum permissible concentration for drinking water in Spain. These two facts have meant the getting under way of a specific plan for monitoring arsenic in the drinking water in the Autonomous Community of Madrid. METHODS: The results of the first two sampling processes conducted in the arsenic level monitoring plan set out are presented. In the initial phase, water samples from 353 water supplies comprised within the census of the Public Health Administration of the Autonomous Community of Madrid were analyzed. A water supply risk classification was made based on these initial results. In a second phase, six months later, the analyses were repeated on those 35 water supplies which were considered to possibly pose a risk to public health. RESULTS: Seventy-four percent (74%) of the water supplies studied in the initial phase were revealed to have an arsenic concentration of less than 10 micrograms/l, 22.6% containing levels of 10 micrograms/l-50 micrograms/l, and 3.7% over 50 micrograms/l. Most of the water supplies showing arsenic levels of more than 10 micrograms/l are located in the same geographical area. In the second sampling process (six months later), the 35 water supplies classified as posing a risk were included. Twenty-six (26) of these supplies were revealed to have the same arsenic level ((10-50 micrograms/l), and nine changed category, six of which had less than 10 micrograms/l and three more than 50 micrograms/l. CONCLUSIONS: In the Autonomous Community of Madrid, less than 2% of the population drinks water coming from supplies which are from underground sources. The regular water quality monitoring conducted by the Public Health Administration has led to detecting the presence of more than 50 micrograms/l of arsenic in sixteen drinking water supplies from underground sources, which is the maximum permissible level under the laws currently in force in Spain. Measures have been taken to prevent water from being used from these water supplies. Around 20% of the water supplies studies must take measures in the near future to lower the arsenic concentration to below 10 micrograms/l when the water directive which is currently in the process of being written into Spanish law enters into effect.
Subject(s)
Arsenic/analysis , Water Pollutants, Chemical/analysis , Water Supply , Spain , Urban HealthABSTRACT
Effects of the antineoplastic agent paclitaxel (Taxol) were studied on contractions of isolated human saphenous vein (HSV) and mammary artery (HMA). Peak force developed by vascular segments with cumulative concentrations of physiologic agonists was enhanced by paclitaxel, producing a shift to the left of dose-response curves. Paclitaxel 1 microM decreased ED50 (in microM) for norepinephrine from 1.01 +/- 0.24 to 0.20 +/- 0.06 (n = 16, p < 0.05) in HSV and from 1.30 +/- 0.30 to 0.51 +/- 0.21 (n = 15, p < 0.05) in HMA and for 5-hydroxytriptamine from 0.64 +/- 0.19 to 0.21 +/- 0.07 (n = 20, p < 0.05) in HSV. Paclitaxel 1 microM also significantly increased the peak force of contractions elicited by endothelin-1 0.01 microM in HSV. In contrast, it did not affect contractions evoked by KCl 80 mM. These results show that paclitaxel produces a hyperreactivity in human vessels challenged by physiologic agonists, which suggests that administration of paclitaxel to patients could augment peripheral resistance and increase blood pressure.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Mammary Arteries/drug effects , Muscle Contraction/physiology , Muscle, Smooth, Vascular/physiology , Paclitaxel/pharmacology , Saphenous Vein/drug effects , Dose-Response Relationship, Drug , Endothelin-1/pharmacology , Female , Humans , Mammary Arteries/physiology , Norepinephrine/pharmacology , Saphenous Vein/physiology , Serotonin/pharmacology , Vascular Resistance/physiologyABSTRACT
The in vitro effect of cyclosporine A (CsA) was studied in reference to the production of reactive oxygen species (peroxides and superoxide anion) and to cell enzyme-mediated antioxidant defence in hepatocytes isolated from rats aged 2 and 12 months. Primary cultures of hepatocytes were incubated in the presence of concentrations of cyclosporine in the range of 0 to 50 microM for 24 hr, and the release of lactate dehydrogenase into the culture medium was evaluated as a parameter of cytotoxicity and membrane lysis. Peroxides were quantified by using 2',7'-dichlorodihydrofluorescein diacetate, and superoxide anion levels were evaluated by the fluorescence of dihydroethidium. Enzyme activity and gene expression of catalase and Mn- and Cu,Zn-superoxide dismutase were also assayed. CsA cytotoxicity was significantly higher in hepatocytes from rats aged 12 months when compared to those aged 2 months. Intracellular peroxide content resulted in a dose-dependent increase, while the anion superoxide intracellular level slightly decreased as CsA increased from 0-50 microM. The progressive increase in intracellular peroxides in cell cultures in the range from 0-50 microM CsA was associated with the loss of cell viability and accompanied by significantly higher levels of Mn- and Cu, Zn-superoxide dismutase enzyme activities and mRNAs, and slight increases in catalase activity and mRNA. We conclude that, in primary hepatocyte cultures, the cytotoxicity of CsA was dose-dependent in both age groups and significantly higher in cultures from 12-month-old rats when compared to those from 2-month-old animals. The non-coordinated regulation of the gene expression of antioxidant enzyme systems, i.e. catalase and Mn- and Cu,Zn-superoxide dismutases, evidenced to a greater extent in hepatocytes from the older group of rats, could be one of the mechanisms involved in CsA toxicity.
Subject(s)
Cyclosporine/pharmacology , Liver/drug effects , Oxidoreductases/metabolism , Age Factors , Analysis of Variance , Animals , Catalase/genetics , Catalase/metabolism , Liver/cytology , Male , Oxidoreductases/genetics , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolismABSTRACT
Two new one-dimensional compounds, trans-[Mn(4-bzpy)2(N(CN)2)2]n (1) and cis-[Mn(bpy)(N(CN)2)2]n (2), have been synthesized and studied from a magnetic point of view (4-bzpy = 4-benzoylpyridine; bpy = 2,2'-bipyridyl). The crystal structures of 1 and 2 have been solved. Compound 1 crystallizes in the monoclinic system, P2(1)/n group, a = 6.374(2) A, b = 7.584(2) A, c = 26.766(5) A, beta = 91.87 degrees, and Z = 2, whereas compound 2 crystallizes in the monoclinic system, C2/c group, a = 6.707(2) A, b = 17.188(5) A, c = 13.096(5) A, beta = 90.54 degrees, and Z = 4. The two compounds consist of chains with double mu 1,5-dicyanamide bridges between neighboring manganese(II) atoms. The weak antiferromagnetic coupling found for the two compounds (J = -0.3 cm-1 for 1 and -0.4 cm-1 for 2) has been studied by MO analysis, and the superexchange pathway through the mu 1,5-(NCNCN-) bridge has been compared with the shorter mu 1,3-(NNN-).