34 results on '"N. Millen"'
Search Results
2. A ready to drink, plant-based oral nutritional supplement is highly complied with, palatable and tolerated in community-based patients at risk of disease-related malnutrition
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C. Griffen, M. Delsoglio, R. Syed, T. Cookson, H. Saliba, A. Vowles, S. Davies, N. Willey, J. Thomas, N. Millen, N. Odeh, J. Longstaff, N. Westran, M. Philllips, L. Allan, H. Offer, C. Howell, M. Sanders, K. Gaffigan, K. Garrett, S. Foster, A. Salt, E. Carter, S. Moore, N. Bergin, J. Roper, J. Alvarez, C. Voss, T. Thrower, C. MacDonald, T. Connolly, D. Sills, J. Baxter, R. Manning, L. Gray, K. Voas, S. Richardson, A.-M. Hurren, D. Murphy, S. Blake, P. McArdle, S. Walsh, L. Booth, L. Albrich, S. Ashley-Maguire, J. Allison, J. McClorey, J. Candlish, S. Brook, R. Capener, G.P. Hubbard, and R.J. Stratton
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Nutrition and Dietetics ,Endocrinology, Diabetes and Metabolism - Published
- 2023
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3. Popliteal vein compression, obesity, and chronic venous disease
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Matthew P.T. Versteeg, Rebecca N. Millen, Andre M. van Rij, and Kate N. Thomas
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Adult ,Male ,medicine.medical_specialty ,Popliteal Vein ,Popliteal fossa ,Adipose tissue ,Constriction, Pathologic ,Popliteal vein ,Internal medicine ,Prevalence ,Medicine ,Humans ,Obesity ,Prospective Studies ,Vascular Diseases ,Risk factor ,Aged ,business.industry ,Ultrasound ,Middle Aged ,medicine.disease ,body regions ,medicine.anatomical_structure ,Chronic Disease ,Cardiology ,Surgery ,Female ,Cardiology and Cardiovascular Medicine ,business ,Lower limbs venous ultrasonography ,Body mass index - Abstract
Background Obesity is a known risk factor for the development of chronic venous disease (CVD). However, some obese patients with lower limb skin changes suggestive of venous disease do not demonstrate venous reflux or obstruction. Popliteal vein compression (PVC) caused by knee hyperextension during standing has been postulated by others to be more common in the obese due to the increased adipose content of the popliteal fossa. This compression may contribute to the development of venous disease. The objective was to examine the prevalence of PVC in obese and nonobese subjects, with and without venous disease. Methods Participants were recruited across the range of Clinical-Etiology-Anatomy-Pathophysiology (CEAP) clinical classifications and body mass. Those referred for venous studies had full venous ultrasound assessments. To assess for PVC, the popliteal vein was assessed via B-mode ultrasound whilst the subject stood and performed two maneuvers: knee hyperextension and a bilateral toe stand. Video clips of each maneuver were analyzed offline. Results There were 309 limbs (158 subjects), of which 131 were nonobese (body mass index [BMI]: 26 ± 3 kg/m2) and 178 obese (BMI: 43 ± 8 kg/m2). PVC with toe stand (PVC(toe stand)) was more common in obese limbs (89% vs 64%, P Conclusions PVC(toe stand) and PVC(lock) are both functional effects and more common in obese limbs. PVC(toe stand) is likely associated with normal functioning of the calf muscle pump. Although PVC(lock) may contribute to CVD in some obese limbs, the demonstration of PVC(lock) alone is insufficient evidence for direct intervention.
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- 2021
4. Improved cardiac outcomes with combined atenolol and diazepam intervention in seizure
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D. S. Kerr, Morgayn I. Read, Rebecca N. Millen, Ivan A. Sammut, Joanne C. Harrison, and Dominic Michael McCann
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Cardiomyopathy ,Status epilepticus ,030204 cardiovascular system & hematology ,QT interval ,Rats, Sprague-Dawley ,Electrocardiography ,03 medical and health sciences ,0302 clinical medicine ,Heart Rate ,Seizures ,Internal medicine ,Heart rate ,medicine ,Animals ,Telemetry ,cardiovascular diseases ,Saline ,Diazepam ,business.industry ,Electroencephalography ,medicine.disease ,Atenolol ,Rats ,Treatment Outcome ,Blood pressure ,Neurology ,Ventricular Fibrillation ,Cardiology ,Anticonvulsants ,Drug Therapy, Combination ,Neurology (clinical) ,medicine.symptom ,business ,Anti-Arrhythmia Agents ,030217 neurology & neurosurgery ,medicine.drug - Abstract
OBJECTIVE Altered autonomic activity has been implicated in the development of cardiac dysfunction during seizures. This study investigates whether intervening in seizure progression with diazepam will reduce seizure-induced cardiomyopathy. Second, this study examines the hypothesis that combining atenolol with diazepam, as an intervention after seizure onset, will combat cardiac injury during status epilepticus. METHODS Male Sprague-Dawley rats were implanted with electroencephalographic/electrocardiographic electrodes to allow simultaneous recordings during seizures induced by intrahippocampal (2 nmol, 1 μL) kainic acid (KA). Subcutaneous saline, atenolol (5 mg·kg-1 ), diazepam (5 mg·kg-1 ), or atenolol and diazepam (n = 12/group) were administered at 60 minutes post-KA and daily for 7 days, at which point echocardiography, susceptibility to aconitine-induced arrhythmias, and histology were evaluated. RESULTS Seizure activity was associated with immediately increased heart rate, QTc interval, and blood pressure (BP; 10%-30% across indices). Seven days postseizure, saline-treated animals were found to have reduced left ventricular function, increased fibrotic scarring, and an elevated risk of aconitine-induced arrhythmias. Diazepam treatment significantly reduced cumulative seizure behaviors by 79% compared to saline-treated animals but offered no cardiac protection. Diazepam significantly raised BP (35%) and increased the risk of bigeminal arrhythmias (36%) compared to saline-treated animals. Atenolol administration, either alone or with diazepam, reduced heart rate, QTc interval, and BP back to control levels. Atenolol also preserved cardiac morphology and reduced arrhythmia risk. SIGNIFICANCE Attenuation of seizure with diazepam offered no cardiac protection; however, coadministration of atenolol with diazepam prevented the development of seizure-induced cardiac dysfunction. This study demonstrates that atenolol intervention should be strongly considered as an adjunct clinical treatment to reduce cardiomyopathy during seizures.
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- 2018
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5. Popliteal Vein Compression, Obesity, and Chronic Venous Insufficiency
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Rebecca N. Millen, Matthew P.T. Versteeg, Andre M. van Rij, Geraldine R Hill, and Kate N. Thomas
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medicine.medical_specialty ,business.industry ,Chronic venous insufficiency ,Popliteal vein ,Internal medicine ,Cardiology ,medicine ,Surgery ,Cardiology and Cardiovascular Medicine ,Compression (physics) ,business ,medicine.disease - Published
- 2020
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6. Progressive development of cardiomyopathy following altered autonomic activity in status epilepticus
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Ivan A. Sammut, Joanne C. Harrison, Morgayn I. Read, Dominic Michael McCann, D. Steven Kerr, and Rebecca N. Millen
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Cardiomyopathy, Dilated ,Male ,Sympathetic nervous system ,Sympathetic Nervous System ,Physiology ,Aconitine ,Cardiomyopathy ,Blood Pressure ,Status epilepticus ,Autonomic Nervous System ,Rats, Sprague-Dawley ,Norepinephrine ,Status Epilepticus ,Heart Rate ,Fibrosis ,Physiology (medical) ,Heart rate ,Excitatory Amino Acid Agonists ,medicine ,Animals ,Myocytes, Cardiac ,Kainic Acid ,business.industry ,Myocardium ,Arrhythmias, Cardiac ,Stroke Volume ,Stroke volume ,Voltage-Gated Sodium Channel Agonists ,medicine.disease ,Rats ,Autonomic nervous system ,Blood pressure ,medicine.anatomical_structure ,Anesthesia ,Vacuoles ,medicine.symptom ,Cardiomyopathies ,Cardiology and Cardiovascular Medicine ,business - Abstract
Seizures are associated with altered autonomic activity, which has been implicated in the development of cardiac dysfunction and structural damage. This study aimed to investigate the involvement of the autonomic nervous system in seizure-induced cardiomyopathy. Male Sprague-Dawley rats (320–350 g) were implanted with EEG/ECG electrodes to allow simultaneous telemetric recordings during seizures induced by intrahippocampal (2 nmol, 1 μl/min) kainic acid and monitored for 7 days. Seizure activity occurred in conjunction with increased heart rate (20%), blood pressure (25%), and QTc prolongation (15%). This increased sympathetic activity was confirmed by the presence of raised plasma noradrenaline levels at 3 h post-seizure induction. By 48 h post-seizure induction, sympathovagal balance was shifted in favor of sympathetic dominance, as indicated by both heart rate variability (LF/HF ratio of 3.5 ± 1.0) and pharmacological autonomic blockade. Functional cardiac deficits were evident at 7 and 28 days, as demonstrated by echocardiography showing a decreased ejection fraction (14% compared with control, P < 0.05) and dilated cardiomyopathy present at 28 days following seizure induction. Histological changes, including cardiomyocyte vacuolization, cardiac fibrosis, and inflammatory cell infiltration, were evident within 48 h of seizure induction and remained present for up to 28 days. These structural changes most probably contributed to an increased susceptibility to aconitine-induced arrhythmias. This study confirms that prolonged seizure activity results in acute and chronic alterations in cardiovascular control, leading to a deterioration in cardiac structure and function. This study further supports the need for modulation of sympathetic activity as a promising therapeutic approach in seizure-induced cardiomyopathy.
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- 2015
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7. Accuracy and repeatability of the Dopplex Ability
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Andre M. van Rij, J Krysa, Brigid G. Hill, Arunesh Majumder, Rebecca N. Millen, and Kate N. Thomas
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Adult ,Male ,Arterial disease ,Biomedical Engineering ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Peripheral Arterial Disease ,0302 clinical medicine ,Medicine ,Plethysmograph ,Humans ,Ankle Brachial Index ,cardiovascular diseases ,030212 general & internal medicine ,Pulse ,Aged ,Aged, 80 and over ,business.industry ,Pulse (signal processing) ,Pulse volume ,General Medicine ,Repeatability ,Middle Aged ,eye diseases ,Peripheral ,body regions ,Plethysmography ,cardiovascular system ,Surgery ,Female ,business ,Biomedical engineering - Abstract
Ankle-brachial index (ABI) and pulse volume recordings (PVR) are non-invasive tests used in diagnosis of peripheral arterial disease (PAD). The Dopplex Ability is an automated ABI/PVR device utilising air plethysmography, offering easy and rapid PAD diagnosis. The accuracy and repeatability of the Dopplex were assessed in comparison to the Doppler/air plethysmography-based Parks Flo-Lab system.Sixty-six patients (n = 129 lower limbs) were assessed with both Dopplex and Parks systems. For Dopplex ABI and PVR to be deemed accurate, it had to be within ±10% of the Parks ABI, and the PVR grade (1-4) had to be equal. The coefficient of variation (CV) was calculated from three repeat ABI/PVR readings to assess repeatability.The Dopplex and Parks devices correlated poorly for ABI (R2 = 0.17) with only 43% of ABIs and 69% of PVRs meeting the accuracy criteria compared to the Parks values. The specificity and sensitivity were 56% and 82%, respectively for ABI, and 91% and 89%, respectively for PVRs. The Dopplex showed a significantly higher CV for both ABIs and PVRs compared to the Parks.We found the Dopplex device to demonstrate suboptimal accuracy and repeatability in assessing ABI/PVR, and it was deemed unsuitable for use in our community.
- Published
- 2018
8. Recuperación Nutricional de Niños Menores de 6 Años en Barrios Periféricos de la Ciudad de Santa Fe
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M. A. González, Liliana E. Contini, M. C. Contini, E. Fernández de Carrera, S. Vaira, N. Millen, and S. T. Mahieu
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- 2006
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9. Función Renal y Eventos Oxidativos en Ratas Machos Adultas con Hepatectomía Parcial
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M. M. Elías, M. C. Contini, N. Millen, M. A. González, and S. Mahieu
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- 2005
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10. [Growth and metabolism of calcium in rats chronically poisoned with aluminium hydroxide]
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S, Mahieu, M L, Calvo, N, Millen, M, Gonzalez, and M C, Contini
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Male ,Parathyroid Glands ,Eating ,Body Weight ,Animals ,Aluminum Hydroxide ,Calcium ,Growth ,Rats, Wistar ,Bone and Bones ,Rats - Abstract
The effects of aluminum on growth have been studied in rats chronically poisoned with aluminum hydroxide (80 mg/kg b.w.-i.p.-three times a week, during 6 months) and in control rats, between 3 and 26 weeks of age. The growth data was evaluated according to Parks 'theory of feeding an growth. At the end of the poisoning period, the calcium metabolism was studied through a balance of calcium and the determination of bone Ca++ accretion and resorption rates with the aid of 45Ca++. The parathyroid glands function was studied using an indirect method. Treated rats showed a significant decrease in asymptotic weights and in the initial efficiency of food conversion into biomass regarding controls. No differences were observed in food intake between both group. Aluminum affected neither the peak growth rate nor the time necessary to attain maturity. The calcium balance in treated rats was significantly less than in the control group. This was accompanied by a significant increase in the calcium excreted by faces, caused perhaps by a less intestinal absorption. An important amount of aluminum on the surface of the trabecular bone and a reduction in the skeletal Ca++ mass, was observed in all treated rats. Nevertheless there are no differences in the latter when expressed for 100 g of body weight. The rate of skeletal Ca++ accretion was found to be significantly decreased in treated group with respect to controls, without any changes in the bone Ca resorption rate. The reduction in bone turnover revealed by the decrease of Vo+/Vo- was accompanied by less recovery velocity of calcemia in the aluminum treated group, being indirectly related to the parathyroid gland response to calcium depletion. In the model that we studied the decreased bone turnover could have been caused by deposits of aluminum in bone; however there could exist associated factors such as dysfunction in the secretion of PTH, or less affinity between its receptors at the bone level.
- Published
- 1998
11. An Investigation into the Effect of Process Control Generated Information on Production Management Organization Structure
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Colin L. Moodie and Roger N. Millen
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Management information systems ,Engineering ,Process management ,Business process ,Production manager ,Process (engineering) ,business.industry ,Interface (computing) ,Control (management) ,Process control ,business ,Management process - Abstract
Two studies, concerned with the use of process control computer-generated information for production management decision making, are discussed. One study which has been completed, used data from a large primary steel products company to study and propose a process control/business control interface. The other study deals with the use of process generated information as a basis for automatic decision making at the lower levels of production management.
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- 1971
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12. An industrial dynamics simulation of the process control/business control interfaces of a large firm
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R. N. Millen
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Engineering ,Instrumentation and control engineering ,business.industry ,Artifact-centric business process model ,Strategy and Management ,Business process modeling ,Industrial engineering ,System model ,Business process management ,Process control ,Electrical and Electronic Engineering ,business ,Simulation ,Management control system ,Advanced process control - Abstract
Using data from a large primary steel products company, two industrial dynamics simulation models were constructed to study the effects of process control computer-generated information on management control systems. The first model represented the existing system, the other a proposed process control/business control interfaced system. The research provides an initial step in the solution of the problem of integrating process control and management control systems by investigating the relationship between process information and control decisions at the operating level of management. The proposed system model indicated much less fluctuation in inventory levels following changes in demand, lower backlog ratios, higher inventory ratios, lower delivery delay ratios, and higher levels of customer satisfaction. The proposed system was also fairly insensitive to changes in the time between transmissions from the process control system to the management control systems once the interface was effected.
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- 1972
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13. Applications Reviews
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Roger N. Millen, John R. Hall, and Vicki L. Sauter
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Management of Technology and Innovation ,Strategy and Management ,Management Science and Operations Research - Abstract
“Applications Reviews” is a guide to accomplished or partial MS/OR applications, cited in articles appearing in many of the major journals of the field. We cover only applications—except for the occasional brief mention of a survey article or special issue—and so do not claim to cover all the best articles in MS/OR. The abstracts are purposely kept short to emphasize breadth of coverage over depth; we try to tell you what modeling approach has been applied to what problem, and if possible the size and character of the improvements achieved as a result.
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- 1982
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14. Applications Reviews
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Roger N. Millen and John R. Hall
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Management of Technology and Innovation ,Strategy and Management ,Management Science and Operations Research - Abstract
An overview of latest results published elsewhere: —Decision Sciences (AIDS), Vol. 9, No. 4, October 1978; —Management Science (TIMS), Vol. 24, No. 11, July 1978; —Management Science, Vol. 24, No. 12, August 1978; —Management Science, Vol. 24, No. 13, September 1978; —MIS Quarterly (SMIS), Vol. 2, No. 3, September 1978; —Operations Research, Vol. 26, No. 5, September–October 1978; —Policy Analysis, Vol. 4, No. 4, Fall 1978.
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- 1980
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15. 'Acceptimization': A Problem of Translation for Management
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Roger N. Millen
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Graduate students ,Operations research ,Management of Technology and Innovation ,Strategy and Management ,Economics ,Production (economics) ,Machine shop ,Management Science and Operations Research ,Marketing - Abstract
A machine shop falls victim to the exacting analysis of an “operations researcher”; the results of the research indicate that the small company must drop several of the items currently being produced and sold. “There are more catalog items than constraints”, the O.R. type explains, “If you only had more constraints on your production!” The manager's response to the thought of seeking to identify more constraints than already existed is omitted in the interests of good taste. A manufacturer of injection-molded dinnerware allowed a group of graduate students in industrial engineering to do a study of their production-inventory system. One of the results was a series of recommendations relating to economic lot size production runs for the various items being produced.
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- 1976
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16. Applications Reviews
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John R. Hall, Roger N. Millen, Vicki L. Sauter, Russell S. Winer, and Charles Dale
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Information retrieval ,Character (mathematics) ,Computer science ,Management of Technology and Innovation ,Strategy and Management ,Cover (algebra) ,Management Science and Operations Research ,Field (geography) - Abstract
“Applications Reviews” is a guide to accomplished or partial MS/OR applications cited in articles appearing in many of the major journals of the field. We cover only applications—except for the occasional brief mention of a survey article or special issue—and so do not claim to cover all the best articles in MS/OR. The abstracts are purposely kept short to emphasize breadth of coverage over depth; we try to tell you what modeling approach has been applied to what problem, and if possible the size and character of the improvements achieved as a result. If an issue of one of our regularly covered journals contains no applications articles, we give the one-line citation for the issue with no articles shown under it. Readers who know of applications articles we may have missed or improperly slighted are invited to let us know. “Applications Reviews” is cosponsored by the TIMS College on Public Programs and Processes, the TIMS College on Marketing, and the ORSA Military Applications Section.
- Published
- 1985
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17. Management Science.
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Hall,Jr., John R., Roger N. Millen, Sauter, Vicki L., Winer, Russell S., and Dale, Charles
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MANAGEMENT science ,OPERATIONS research ,DISCRIMINANT analysis ,MULTIVARIATE analysis - Abstract
This article presents abstracts of articles on management science. The article "Introduction Strategy for New Products With Positive and Negative Word-of-Mouth," published in the journal "Management Science," presents a diffusion model that derives recommendations for advertising timing and forecasts sales in cases where word-of-mouth information may be negative or positive. The model has been tested in the real world on attendance for the film "Gandhi" in the Dallas area, but it has not yet been truly applied to a problem where some client wanted answers. Funding for the research came from Procter & Gamble, which may have had occasion to apply the method in view of their problems with recurring accusations of Satanism. According to the article "A Robust Credit Screening Model Using Categorical Data," published in the journal "Management Science," a decision theory framework is used to generate a mathematical programming approach for an AT&T application where the assumptions required by the standard classical linear discriminant analysis approach are not satisfied.
- Published
- 1985
18. Journal of the Operational Research Society.
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Hall,Jr., John R., Roger N. Millen, Sauter, Vicki L., Winer, Russell S., and Dale, Charles
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MANAGEMENT science ,OPERATIONS research ,DECISION theory ,DECISION support systems ,DECISION making - Abstract
This article presents an abstract of the article "An Operational Research Approach to Planned Maintenance: Modeling P.M. for a Vehicle Fleet," published in the "Journal of the Operational Research Society." The article presents a model for preventive maintenance for a fleet of tractor units operated by Hiram Walker Ltd. Authors of the article examine the type of data needed to answer questions about the omission of necessary items and inclusion of unnecessary items from the maintenance schedule.
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- 1985
19. Computers and Operations Research/European Journal of Operational Research/European Journal of Operational Research.
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Hall,Jr., John R., Roger N. Millen, Sauter, Vicki L., Winer, Russell S., and Dale, Charles
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MANAGEMENT science ,BLOOD banks ,OPERATIONS research ,DECISION theory ,MANAGEMENT ,PERIODICALS - Abstract
This article presents an abstract of the article "Analytical Evaluation of the Characteristic Curve of a Blood Bank and Its Usefulness in Blood Banking," published in the journal "Computers and Operations Research." According to the article blood that is not used fairly quickly becomes outdated and wasted, so it is important to know how much a blood bank should keep in inventory. The author analyzes data from a Scottish teaching hospital in this blood bank model, which consists of appropriately named renewal processes.
- Published
- 1985
20. A multi-center prospective study of plant-based nutritional support in adult community-based patients at risk of disease-related malnutrition.
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Delsoglio M, Griffen C, Syed R, Cookson T, Saliba H, Vowles A, Davies S, Willey N, Thomas J, Millen N, Odeh N, Longstaff J, Westran N, Allan L, Offer H, Howell C, Sanders M, Gaffigan K, Garrett K, Foster S, Salt A, Carter E, Moore S, Bergin N, Roper J, Alvarez J, Voss C, Connolly T, MacDonald C, Thrower T, Sills D, Baxter J, Manning R, Gray L, Voas K, Richardson S, Hurren AM, Murphy D, Blake S, McArdle P, Walsh S, Booth L, Albrich L, Ashley-Maguire S, Allison J, Brook S, Capener R, Hubbard GP, and Stratton RJ
- Abstract
Introduction: There is an emerging need for plant-based, vegan options for patients requiring nutritional support., Methods: Twenty-four adults at risk of malnutrition (age: 59 years (SD 18); Sex: 18 female, 6 male; BMI: 19.0 kg/m
2 (SD 3.3); multiple diagnoses) requiring plant-based nutritional support participated in a multi-center, prospective study of a (vegan suitable) multi-nutrient, ready-to-drink, oral nutritional supplement (ONS) [1.5 kcal/mL; 300 kcal, 12 g protein/200 mL bottle, mean prescription 275 mL/day (SD 115)] alongside dietary advice for 28 days. Compliance, anthropometry, malnutrition risk, dietary intake, appetite, acceptability, gastrointestinal (GI) tolerance, nutritional goal(s), and safety were assessed., Results: Patients required a plant-based ONS due to personal preference/variety (33%), religious/cultural reasons (28%), veganism/reduce animal-derived consumption (17%), environmental/sustainability reasons (17%), and health reasons (5%). Compliance was 94% (SD 16). High risk of malnutrition ('MUST' score ≥ 2) reduced from 20 to 16 patients ( p = 0.046). Body weight (+0.6 kg (SD 1.2), p = 0.02), BMI (+0.2 kg/m2 (SD 0.5), p = 0.03), total mean energy (+387 kcal/day (SD 416), p < 0.0001) and protein intake (+14 g/day (SD 39), p = 0.03), and the number of micronutrients meeting the UK reference nutrient intake (RNI) (7 vs. 14, p = 0.008) significantly increased. Appetite (Simplified Nutritional Appetite Questionnaire (SNAQ) score; p = 0.13) was maintained. Most GI symptoms were stable throughout the study ( p > 0.06) with no serious adverse events related., Discussion: This study highlights that plant-based nutrition support using a vegan-suitable plant-based ONS is highly complied with, improving the nutritional outcomes of patients at risk of malnutrition., Competing Interests: MD, CG, RC, GPH and RJS were employed by Nutricia Ltd. The authors declare that this study received funding from Nutricia Ltd. The funder had the following involvement in the study: study design, data analysis, preparation of the manuscript and decision to publish. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Delsoglio, Griffen, Syed, Cookson, Saliba, Vowles, Davies, Willey, Thomas, Millen, Odeh, Longstaff, Westran, Allan, Offer, Howell, Sanders, Gaffigan, Garrett, Foster, Salt, Carter, Moore, Bergin, Roper, Alvarez, Voss, Connolly, MacDonald, Thrower, Sills, Baxter, Manning, Gray, Voas, Richardson, Hurren, Murphy, Blake, McArdle, Walsh, Booth, Albrich, Ashley-Maguire, Allison, Brook, Capener, Hubbard and Stratton.)- Published
- 2023
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21. Differences in suppression of regrowth and resistance despite similar initial bacterial killing for meropenem and piperacillin/tazobactam against Pseudomonas aeruginosa and Escherichia coli.
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Bergen PJ, Bulitta JB, Sime FB, Lipman J, McGregor MJ, Millen N, Paterson DL, Kirkpatrick CMJ, Roberts JA, and Landersdorfer CB
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- Escherichia coli growth & development, Escherichia coli isolation & purification, Humans, Meropenem, Microbial Sensitivity Tests, Penicillanic Acid analogs & derivatives, Penicillanic Acid pharmacology, Piperacillin pharmacology, Piperacillin, Tazobactam Drug Combination, Pseudomonas aeruginosa growth & development, Pseudomonas aeruginosa isolation & purification, Thienamycins pharmacology, beta-Lactam Resistance, Anti-Bacterial Agents pharmacology, Escherichia coli drug effects, Escherichia coli Infections microbiology, Pseudomonas Infections microbiology, Pseudomonas aeruginosa drug effects, beta-Lactamase Inhibitors pharmacology
- Abstract
We described bacterial killing and resistance emergence at various fixed concentrations of meropenem and piperacillin/tazobactam against Pseudomonas aeruginosa and Escherichia coli. Time-kill studies were conducted utilizing nine isolates and a large range of concentrations. Within each strain and antibiotic, initial killing was similar, with concentrations ≥2×MIC. At many (strain-specific) concentrations causing substantial initial killing, regrowth occurred at 24-48h. For remaining concentrations, growth typically remained suppressed (<5-log
10 cfu/mL). The concentrations of meropenem required to suppress regrowth ranged from 2-8×MIC for P. aeruginosa and 2-64×MIC for E. coli. For piperacillin/tazobactam, the equivalent concentrations ranged from 8-16×MIC for P. aeruginosa and 4-16×MIC for E. coli. The number of less-susceptible bacteria increased with rising concentrations before decreasing at even higher concentrations. Suppression of regrowth and resistance was substantially improved with higher concentrations (typically ≥8×MIC), suggesting a benefit of higher β-lactam concentrations beyond those required for maximum initial killing., (Copyright © 2018. Published by Elsevier Inc.)- Published
- 2018
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22. Adverse effects in kidney function, antioxidant systems and histopathology in rats receiving monosodium glutamate diet.
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Contini MDC, Fabro A, Millen N, Benmelej A, and Mahieu S
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- Animals, Male, Rats, Rats, Wistar, Flavoring Agents toxicity, Kidney drug effects, Oxidative Stress drug effects, Sodium Glutamate toxicity
- Abstract
We investigated the effects of adding of monosodium glutamate (MSG) to a standard diet on oxidative stress in kidney, nitric oxide excretion, renal ions handling and blood pressure. We examined the association of these changes with the effects on renal histology. The study was performed on male Wistar rats (5 weeks old) divided into 3 groups: 1) MSG group were fed a diet supplemented with 3g of MSG/kg b.w./day, five days a week, and spontaneous ingestion of a 1% MSG solution during 16 weeks; 2) NaCl group were fed a diet with NaCl (1g/kg b.w./day) and 0.35% NaCl solution permanently alone at the same frequency and time; 3) control group were fed the normal chow and tap water. Sodium, potassium, calcium, phosphorus, creatinine, protein and nitric oxide excretion were analyzed in urine. We utilized clearance techniques to examine glomerular filtration rate and cortical renal plasma flow. We determined the oxidative state and the histopathological changes of renal tissue. Following MSG treatment, absolute and fractional sodium and potassium excretion decreased although there was hyperfiltration. The MSG group showed similar increase in blood pressure than the NaCl group, but nitric oxide excretion was significantly reduced. Although no increase in lipid peroxidation was verified, its observed alteration in the reduced glutathione/oxidized cycle and their enzymes GPx and GR. These changes were accompanied by alterations histological both glomerular as well as tubular level and by interstitial fibrosis with mononuclear cells accumulation. These results indicate that the addition of MSG in the diet decreases the excretion of Na, K and water with hyperfiltration. NaCl retention that leads to hypertension was accompanied by renal pathologic changes, intrarenal oxidative stress and reduction of nitric oxide excretion., (Copyright © 2017 Elsevier GmbH. All rights reserved.)
- Published
- 2017
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23. Orchiectomy attenuates oxidative stress induced by aluminum in rats.
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Contini MD, Millen N, González M, Benmelej A, Fabro A, and Mahieu S
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- Aluminum administration & dosage, Animals, Drug Resistance, Environmental Pollutants administration & dosage, Glutathione metabolism, Hormone Replacement Therapy adverse effects, Injections, Intraperitoneal, Kidney metabolism, Kidney pathology, Kidney physiopathology, Lipid Peroxidation drug effects, Male, Metals, Heavy blood, Metals, Heavy metabolism, Orchiectomy adverse effects, Oxidation-Reduction, Oxidoreductases metabolism, Poisoning blood, Poisoning metabolism, Poisoning pathology, Random Allocation, Rats, Wistar, Renal Insufficiency etiology, Renal Insufficiency prevention & control, Testis drug effects, Testis physiopathology, Testosterone adverse effects, Testosterone blood, Testosterone therapeutic use, Aluminum toxicity, Environmental Pollutants toxicity, Heavy Metal Poisoning, Kidney drug effects, Oxidative Stress drug effects, Poisoning physiopathology, Testis metabolism, Testosterone metabolism
- Abstract
The aim of this work was to study whether the increase in antioxidant defenses associated with orchiectomy may account for the reduced susceptibility to aluminum (Al) in male kidney and also to examine whether the reduced antioxidant defenses are associated with androgen levels in orchiectomized (ORX) rats treated with testosterone propionate (TP). Rats were divided into nine groups, namely, intact males (without treatment, treated with sodium lactate, and treated with Al), sham males, ORX males (without treatment, treated with sodium lactate, treated with TP, treated with Al, and treated with TP and Al). Al groups were chronically treated with aluminum lactate for 12 weeks (0.575 mg Al/100 g of body weight, intraperitoneally, three times per week). We reported that ORX rats treated with Al had significantly less lipid peroxidation and an increased level of reduced glutathione (GSH) and GSH/oxidized glutathione ratio in the kidney when compared with intact and TP-treated ORX rats. The activity of superoxide dismutase, catalase, and glutathione peroxidase in ORX rats was much greater than in intact or TP-administered ORX rats. Castration reduced the glomerular alterations caused by Al as well as the number of necrotic tubular cells and nuclear abnormalities. However, we observed a slight alteration in brush border, dilation of proximal tubules, mononuclear infiltrates, and interstitial fibrosis. Castrated males treated with TP showed that this intervention cancels the protective effect of the ORX. This finding suggests that androgens contribute to the development of renal alterations and proteinuria in rats treated with Al. Our results showed that ORX rats are protected against the induction of oxidative stress by Al, but the morphological damage to the kidney tissue induced by the cation was only reduced. Male intact rats treated with Al had more severe glomerulosclerosis, tubular damage, and proteinuria than ORX rats., (© The Author(s) 2015.)
- Published
- 2016
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- View/download PDF
24. Monosodium glutamate intake affect the function of the kidney through NMDA receptor.
- Author
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Mahieu S, Klug M, Millen N, Fabro A, Benmelej A, and Contini Mdel C
- Subjects
- Animals, Dizocilpine Maleate pharmacology, Glomerular Filtration Rate drug effects, Glomerular Filtration Rate physiology, Kidney chemistry, Male, Rats, Rats, Wistar, Receptors, N-Methyl-D-Aspartate antagonists & inhibitors, Kidney drug effects, Kidney physiology, Receptors, N-Methyl-D-Aspartate analysis, Receptors, N-Methyl-D-Aspartate biosynthesis, Sodium Glutamate administration & dosage
- Abstract
Aims: We investigated whether the chronic intake of monosodium glutamate (MSG) with food affects kidney function, and renal response to glycine. We also established if the NMDA receptors are involved in the changes observed., Main Methods: Male Wistar rats (5weeks old) were fed a diet supplemented with MSG (3g/kg b.w./day), five days a week, and spontaneous ingestion of a 1% MSG solution during 16weeks. NaCl rats were fed a diet with NaCl (1g/kg b.w./day) and 0.35% NaCl solution at the same frequency and time. Control group was fed with normal chow and tap water. We utilized clearance techniques to examine glomerular filtration rate (GFR) and cortical renal plasma flow (CRPF) response to glycine and glycine+MK-801 (antagonist NMDA-R), and we determined NMDA-R1 in kidney by immunohistochemistry., Key Findings: The addition of MSG in the diet of rats increased both GFR and CRPF with an increase of absolute sodium reabsorption. However, hyperfiltration was accompanied with a normal response to glycine infusion. Immunostain of kidney demonstrate that the NMDA receptor is upregulated in rats fed with MSG diet. NMDA-R antagonist MK-801 significantly reduced both the GFR and CRPF; however the percentage of reduction was significantly higher in the group MSG. MK-801 also reduces fractional excretion of water, sodium and potassium in the three groups., Significance: Renal NMDAR may be conditioned by the addition of MSG in the diet, favoring the hyperfiltration and simultaneously Na retention in the body., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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25. Role of melatonin in the oxidative damage prevention at different times of hepatic regeneration.
- Author
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González MA, Contini Mdel C, Millen N, and Mahieu ST
- Subjects
- Algorithms, Animals, Antioxidants pharmacology, Area Under Curve, Biliary Tract drug effects, Biliary Tract metabolism, Biliary Tract physiology, Catalase metabolism, Coloring Agents pharmacokinetics, Glutathione Peroxidase metabolism, Hepatectomy methods, Humans, Lipid Peroxidation drug effects, Liver physiopathology, Liver surgery, Male, Metabolic Clearance Rate, Rats, Rats, Wistar, Sodium-Potassium-Exchanging ATPase metabolism, Sulfobromophthalein pharmacokinetics, Time Factors, Liver drug effects, Liver Regeneration drug effects, Melatonin pharmacology, Oxidative Stress drug effects
- Abstract
The process of regenerating liver is the result of a balance between stimulating factors and inhibitors of hepatocyte proliferation. Melatonin and its metabolites have been found to protect tissues against oxidative damage generated by a variety of toxic agents and metabolic processes. Furthermore, studies in liver of rats showed a decrease in the liver mitochondrial hydroxylation of drugs returning to the normal state after the administration of antioxidants. This study was designed to determine, in experimental animals, whether the administration of an antioxidant agent such as melatonin could prevent cells events leading to tissue injury and hepatic dysfunction after partial hepatectomy (PH). Biliary flow (BF), oxidative stress in hepatic tissue and Na⁺/K⁺ ATPase activities in whole plasma membrane were determined. PH decreased the Na⁺/K⁺ ATPase activity. PH significantly reduced the BF (36%) and promoted oxidative stress with an increase of lipoperoxidation and decrease of glutathione peroxidase and catalase activities. Treatment with melatonin prevented the decrease of BF in rats with hepatectomy and normalized the Na⁺/K⁺ ATPase activity. Moreover, melatonin markedly attenuated oxidative stress produced by PH. This may be the results of the higher efficacy of melatonin in scavenging various free radicals and also because of its ability in stimulating the antioxidant enzymes. We suggest that oxidative stress before and during liver regeneration has a crucial role in cholestasis, apoptotic/necrotic hepatocellular damage and the impairment in liver transport function induced by PH and that melatonin could modulate the degree of oxidative stress and through it prevent the alterations in liver function carrier., (Copyright © 2012 John Wiley & Sons, Ltd.)
- Published
- 2012
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26. Melatonin prevents oxidative stress in ovariectomized rats treated with aluminium.
- Author
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Contini Mdel C, Millen N, González M, and Mahieu S
- Subjects
- Aldosterone blood, Aluminum Compounds pharmacology, Animals, Body Weight drug effects, Female, Guanosine Triphosphate metabolism, Kidney drug effects, Kidney metabolism, Kidney Concentrating Ability drug effects, Lactates pharmacology, Liver drug effects, Liver metabolism, Organ Size drug effects, Osmolar Concentration, Photometry, Rats, Rats, Wistar, Sodium-Potassium-Exchanging ATPase metabolism, Urodynamics drug effects, Uterus drug effects, Water metabolism, Aluminum antagonists & inhibitors, Aluminum toxicity, Antioxidants pharmacology, Melatonin pharmacology, Ovariectomy, Oxidative Stress drug effects
- Abstract
This study is designed to determine the simultaneous effect of aluminium (Al) and melatonin (Mel) treatment in intact and ovariectomized (Ovx) female rats on oxidative stress and their inter-organ relationship in the kidney and liver. Al-treated rats received an intra-peritoneal injection of solution of aluminium lactate (0.575 mg Al/100 g of body weight, three times a week), during 12 weeks. Mel groups received intra-peritoneal injections of melatonin at a dose of 10 mg/kg/day, 5 days/week, during 12 weeks. The results of this study showed that Al treatment in female rats modifies homeostasis of glutathione and the antioxidant capacity of the rat liver and kidney. The alteration of glutathione homeostasis and oxidative status was not associated with an increased lipid peroxidation in both organs with the exception of the increase observed in the liver of Ovx rats. Al also induced modifications in the activity of some enzymes related to the glutathione cycle: GSH-Px in the liver and kidney and glutathione reductase only in the kidney. Al exposure decreased CAT activity in both the kidney and liver of intact and Ovx groups. The administration of Mel in the intact and castrated females treated with Al seems to reduce oxidative changes in the liver and kidney of intact and Ovx rats.
- Published
- 2011
- Full Text
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27. Melatonin reduces oxidative damage induced by aluminium in rat kidney.
- Author
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Mahieu S, Contini Mdel C, González M, and Millen N
- Subjects
- Aluminum blood, Aluminum pharmacokinetics, Animals, Antioxidants therapeutic use, Cell Membrane drug effects, Cell Membrane enzymology, Cell Membrane metabolism, Cyclic AMP metabolism, Kidney enzymology, Kidney metabolism, Kidney Function Tests, Lipid Peroxides metabolism, Male, Melatonin therapeutic use, Rats, Rats, Wistar, Renal Insufficiency metabolism, Renal Insufficiency prevention & control, Sodium-Potassium-Exchanging ATPase metabolism, Urinalysis, Aluminum toxicity, Antioxidants pharmacology, Kidney drug effects, Melatonin pharmacology, Oxidative Stress drug effects
- Abstract
We evaluated the effect of melatonin (Mel), in male Wistar rats which received aluminium (Al) lactate for 12 weeks (0.57 mg Al/100g body weight (b.w.), i.p. three times per week). Moreover rats received Mel (10 mg/kg b.w. i.p. 5 days/weeks) for 12 weeks. At the end of the treatment water and sodium balances were studied, and nephrogenic cyclic adenosine monophosphate (cAMP) was also measured. Urinary osmolality was measured after the administration of desmopressin (vasopressin agonist) to assess concentrating capacity. Oxidative stress in renal tissue and Na(+)-K(+)ATPase and gamma-glutamyl transferase (GGT) activities in whole plasma membrane were determined. Sodium and water balances were impaired by Al. We found decreased urinary concentrating ability and nephrogenic cAMP excretion. Al increased the Na(+)-K(+)ATPase activity, and serum aldosterone concentration. Mel normalized serum aldosterone level, the Na(+)-K(+)ATPase activity and potassium urinary without improving water and sodium excretion. Mel treatment did not improve the impaired urinary concentrating ability. Al reduced the GGT activity, an effect that persists in Al(+) Mel. Al exposure promoted oxidative stress with an increase in lipid peroxidation (LPO), and a decrease in glutathione (GSH) and glutathione peroxidase (GSH-Px) and catalase (CAT) activities. Mel markedly attenuated oxidative stress produced by Al. This may result from the higher efficacy of melatonin in scavenging various free radicals and also because of its ability in stimulating the antioxidant enzymes. However, it only reduced some alterations in the renal functions particularly related to the water and sodium excretion, which would be independent of the increased production of reactive oxygen substances.
- Published
- 2009
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28. Urinary concentrating mechanism and Aquaporin-2 abundance in rats chronically treated with aluminum lactate.
- Author
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Mahieu S, Millen N, Contini Mdel C, Gonzalez M, Molinas SM, and Elías MM
- Subjects
- Animals, Deamino Arginine Vasopressin pharmacology, Drinking Behavior, Kidney Tubules metabolism, Kidney Tubules physiopathology, Male, Protein Transport, Rats, Rats, Wistar, Saline Solution, Hypertonic, Time Factors, Urinalysis, Aluminum Compounds toxicity, Aquaporin 2 metabolism, Kidney Concentrating Ability drug effects, Kidney Tubules drug effects, Lactates toxicity
- Abstract
The aim of this work was to study the effects of chronic administration of aluminum (Al) on the urinary concentrating and diluting mechanisms in the distal tubules and collecting ducts. Male Wistar rats were chronically treated with aluminum lactate for 12 weeks (0.575 mg Al/100g of body weight, i.p., three times per week). After 12 weeks, renal function of control and Al-treated rats was evaluated by clearance techniques. To study urinary concentrating mechanisms, renal function was also measured in control and Al-treated rats deprived of water, after the administration of desmopressin (vasopressin agonist) and after the infusion of hypertonic saline at increasing infusion rates. Sodium and water balance were impaired. We found decreased urinary concentrating ability in situations in which endogenous (thirst or infusion of hypertonic saline) or exogenous plasma antidiuretic hormone was increased. Solute-free water formation, measured during the infusion of hypotonic saline showed normal transport in the thick ascending limb. Aquaporin-2 (AQP2) expression was measured by Western blot to evaluate water permeability in collecting ducts. We found that Al produced downregulation of AQP2 in plasma membranes and intracellular vesicles, that could account for the impaired water handling. Administration of desmopressin increased AQP2 in plasma membranes, suggesting that Al did not impair trafficking of this protein, but could interfere with AQP2 synthesis.
- Published
- 2006
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29. Alterations of the renal function and oxidative stress in renal tissue from rats chronically treated with aluminium during the initial phase of hepatic regeneration.
- Author
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Mahieu S, Millen N, González M, Contini Mdel C, and Elías MM
- Subjects
- Animals, Hepatectomy, Kidney Cortex enzymology, Kidney Cortex metabolism, Kidney Cortex physiopathology, Male, Rats, Rats, Wistar, Sodium-Potassium-Exchanging ATPase metabolism, Kidney Cortex drug effects, Kidney Function Tests, Liver Regeneration drug effects, Oxidative Stress
- Abstract
Various indices of renal functions during the early stage of hepatic injury were studied in rats chronically treated with aluminum (Al) lactate. Tubular and hemodynamic parameters were analyzed four days after producing a 65% partial hepatectomy (PH). Water and sodium balances were also studied. Oxidative stress and the activity of Na-K-ATPase were determined in renal tissue. The rats were distributed in four groups: control, Al, PH, Al+PH. Al did not modify the hemodynamic renal functions and the PH-group reduced the glomerular filtrate rate (GFR). The Al + PH group presented a decrease in the renal blood flow and accentuated the GFR fall as compared with PH. The fractional excretion (FE) of water and sodium increased in the PH group. The rats chronically treated with Al and then submitted to the PH protocol developed a further increase in FE of water but a reduction in FE of sodium. Both PH and Al promoted an increase in the aldosterone. PH and Al induced a similar increase of the lipoperoxidation status with reduction of glutathione (GSH) and the activity of glutathione peroxidase (GSH-Px). The data indicated that Al is an inhibitor of catalase. The GSH and GSH-Px activity in the Al + PH group demonstrated a synergic effect of Al and PH. This work demonstrates that rats treated chronically with Al and submitted to another injury (such as hepatic damage) can aggravate renal functions, probably by increasing the oxidative state, at least in kidneys.
- Published
- 2005
- Full Text
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30. Cytidine deaminase in polymyalgia rheumatica and elderly onset rheumatoid arthritis.
- Author
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Paira S, Roverano S, Rillo O, Barrionuevo A, Mahieu S, and Millen N
- Subjects
- Aged, Arthritis, Rheumatoid enzymology, Biomarkers blood, Clinical Enzyme Tests, Female, Humans, Male, Middle Aged, Polymyalgia Rheumatica enzymology, Arthritis, Rheumatoid diagnosis, Cytidine Deaminase blood, Polymyalgia Rheumatica diagnosis
- Abstract
Serum cytidine deaminase (CD) as a marker of inflammatory disease was assessed in 44 patients and 47 controls to differentiate polymyalgia rheumatica (PMR) from elderly onset rheumatoid arthritis (EORA). The patients were divided into four groups: PMR with and without synovitis and seropositive and seronegative EORA. No statistically significant differences were found when serum CD levels of seropositive EORA patients were compared with serum CD of PMR patients without synovitis, neither when serum CD levels of all PMR patients were compared with a seronegative EORA group, nor when serum CD levels of PMR patients with synovitis were compared with those with EORA. Nevertheless, statistically significant differences were detected between EORA's serum CD levels and the control group (p=0.023). This difference was 10% when comparing CD levels of PMR patients with the control group (p=0.070). We did not demonstrate that serum CD levels could be a useful tool to differentiate PMR from EORA, but these findings could nevertheless reflect the presence of an inflammatory disease.
- Published
- 2005
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31. Effects of aluminum on phosphate metabolism in rats: a possible interaction with vitamin D3 renal production.
- Author
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Mahieu ST, Navoni J, Millen N, del Carmen Contini M, Gonzalez M, and Elías MM
- Subjects
- Animals, Calcitriol pharmacology, Calcium metabolism, Feces chemistry, Femur drug effects, Femur metabolism, Injections, Intraperitoneal, Intestinal Absorption drug effects, Jejunum drug effects, Jejunum metabolism, Male, Phosphorus urine, Phosphorus Radioisotopes, Rats, Rats, Wistar, Tibia drug effects, Tibia metabolism, Aluminum Compounds toxicity, Calcitriol metabolism, Kidney metabolism, Lactates toxicity, Phosphorus metabolism
- Abstract
The effect of chronic aluminum (Al) administration on the phosphorous (Pi) metabolism of different target tissues was studied. Male Wistar rats received aluminum lactate for 3 months (5.75 mg/kg bodyweight of Al, i.p., three times per week). The animals were studied at the end of the 1st, 2nd and 3rd month of treatment. They were housed individually in metabolic cages for 4 days to study Pi and calcium (Ca) balance. Daily food and water intakes were recorded for all animals and urine and feces were collected for Pi and calcium assays. After 3 months the Pi intestinal absorption and the Pi deposition in bone were studied using 32Pi. Another group of rats was treated daily for 7 days with calcitriol (0.08 microg/kg body weight in sesame oil, i.p.) and the Pi balance was studied for the last 4 days. The results indicated that chronic administration of Al affected simultaneously the Pi and calcium balance, with a significant diminution of calcium and increased Pi accretion in bones, together with a diminution in the intestinal absorption of Pi. The treatment of the rats with calcitriol promoted a normalized Pi balance in Al treated rats. These findings suggest that Al could modify the Pi metabolism acting directly on intestine, kidney and bone, or indirectly through possible changes in the levels of vitamin D3.
- Published
- 2004
- Full Text
- View/download PDF
32. Effect of chronic accumulation of aluminum on renal function, cortical renal oxidative stress and cortical renal organic anion transport in rats.
- Author
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Mahieu ST, Gionotti M, Millen N, and Elías MM
- Subjects
- Aluminum pharmacokinetics, Animals, Body Weight drug effects, Glutathione metabolism, Glutathione Transferase metabolism, In Vitro Techniques, Kidney cytology, Kidney Function Tests, Male, Mercuric Chloride toxicity, Organ Size drug effects, Osmolar Concentration, Rats, Rats, Wistar, Water-Electrolyte Balance drug effects, p-Aminohippuric Acid metabolism, Aluminum toxicity, Kidney drug effects, Kidney Cortex metabolism, Organic Anion Transporters metabolism, Oxidative Stress drug effects
- Abstract
The aim of the present work was to study the nephrotoxicity of aluminum lactate administered for 3 months (0.57 mg/100 g bodyweight aluminum, i.p., three times per week) to male Wistar rats. Renal function was studied after 6 weeks of treatment (urine was obtained from rats in metabolic cages) and at the end of the treatment using clearance techniques. Another group of rats was used as kidneys donors at the end of treatment. The renal cortex was separated and homogenized to determine glutathione (GSH) level, glutathione S-transferase (GST) activity and lipid peroxidation (LPO) level. Renal cortex slices were also used to study the p-aminohippuric acid (PAH) accumulation during steady-state conditions and the kinetics of uptake process. Clearance results, at the end of the treatment, indicated that renal functions in treated-rats were not different from those measured in control rats, although the renal concentration parameters differ when they were measured in treated rats after 24 h of food and water deprivation. Balances of water and sodium were also modified at both 1.5 and 3 months of treatment. The activity of alkaline phosphatase (AP) relative to inulin excreted in urine was significantly impaired: controls 2.2+/-0.6 IUI/mg, Al-treated 5.1+/-0.5 IU/mg, P<0.05. These data indicated that proximal tubular cells were loosing apical brush border membranes. Data obtained in cortex homogenates indicated that both GSH and GST activity were significantly decreased, and a significant increase of LPO was noted simultaneously in Al-treated rats. Renal accumulation of PAH, estimated as slice-to-medium ratio, decreased significantly in the Al-treated rats: control rats 3.06+/-0.02 ( n=12), Al-treated rats 2.26+/-0.04 ( n=12), P<0.0001. The maximal rate of uptake was also diminished in treated rats, while the apparent affinity remained unchanged. All these results indicate that aluminum accumulation in renal tissue affects cellular metabolism, promotes oxidative stress and induces alterations in renal tubular PAH transport, together with an impairment in sodium and water balance only detected under conditions of water deprivation, without other evident changes in glomerular filtration rate or other global functions measured by clearance techniques at least at this time of chronic toxicity.
- Published
- 2003
- Full Text
- View/download PDF
33. Aluminum toxicity. Hematological effects.
- Author
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Mahieu S, del Carmen Contini M, Gonzalez M, Millen N, and Elias MM
- Subjects
- Aluminum Hydroxide blood, Animals, Diet, Erythrocyte Count drug effects, Erythrocyte Indices drug effects, Hematocrit, Hemoglobins metabolism, Injections, Intraperitoneal, Iron blood, Iron metabolism, Kidney drug effects, Kidney Function Tests, Male, Rats, Rats, Wistar, Aluminum Hydroxide toxicity, Blood drug effects
- Abstract
Sequential effects of intoxication with aluminum hydroxide (Al) (80 mg/Kg body weight, i.p., three times a week), were studied on rats from weaning and up to 28 weeks. The study was carried out on hematological and iron metabolism-related parameters on peripheral blood, at the end of the 1st, 2nd, 3rd, 4th, 5th and 6th months of exposure. As it was described that hematotoxic effects of Al are mainly seen together with high levels of uremia, renal function was measured at the same periods. The animals treated developed a microcytosis and was accompanied by a decrease in mean corpuscular hemoglobin (MCH). Significantly lower red blood cell counts (RBC million/microl) were found in rats treated during the 1st month. These values matched those obtained for control rats during the 2nd month. From the 3rd month onwards, a significant increase was observed as compared to control groups, and the following values were obtained by the 6th month: (T) 10.0 +/- 0.3 versus (C) 8.7 +/- 0.2 (million/microl). Both MCH and mean corpuscular volume (MCV) were found to be significantly lower in groups treated from the 2nd month. At the end of the 6th month the following values were found: MCH (T) 13.3 +/- 0.1 versus (C) 16.9 +/- 0.3 (pg); MCV (T) 42.1 +/- 0.7 versus (C) 51.8 +/- 0.9 (fl). Al was found responsible for lower serum iron concentration levels and in the percentage of transferrin saturation. Thus, although microcytic anemia constitutes an evidence of chronic aluminum exposure, prolonged exposure could lead to a recovery of hematocrit and hemoglobin concentration values with an increase in red cell number. Nevertheless, both microcytosis and the decrease of MCH would persist. These modifications took place without changes being observed in the renal function during the observation period.
- Published
- 2000
- Full Text
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34. [Growth and metabolism of calcium in rats chronically poisoned with aluminium hydroxide].
- Author
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Mahieu S, Calvo ML, Millen N, Gonzalez M, and Contini MC
- Subjects
- Animals, Body Weight drug effects, Bone and Bones drug effects, Eating drug effects, Growth physiology, Male, Parathyroid Glands drug effects, Rats, Rats, Wistar, Aluminum Hydroxide poisoning, Calcium metabolism, Growth drug effects
- Abstract
The effects of aluminum on growth have been studied in rats chronically poisoned with aluminum hydroxide (80 mg/kg b.w.-i.p.-three times a week, during 6 months) and in control rats, between 3 and 26 weeks of age. The growth data was evaluated according to Parks 'theory of feeding an growth. At the end of the poisoning period, the calcium metabolism was studied through a balance of calcium and the determination of bone Ca++ accretion and resorption rates with the aid of 45Ca++. The parathyroid glands function was studied using an indirect method. Treated rats showed a significant decrease in asymptotic weights and in the initial efficiency of food conversion into biomass regarding controls. No differences were observed in food intake between both group. Aluminum affected neither the peak growth rate nor the time necessary to attain maturity. The calcium balance in treated rats was significantly less than in the control group. This was accompanied by a significant increase in the calcium excreted by faces, caused perhaps by a less intestinal absorption. An important amount of aluminum on the surface of the trabecular bone and a reduction in the skeletal Ca++ mass, was observed in all treated rats. Nevertheless there are no differences in the latter when expressed for 100 g of body weight. The rate of skeletal Ca++ accretion was found to be significantly decreased in treated group with respect to controls, without any changes in the bone Ca resorption rate. The reduction in bone turnover revealed by the decrease of Vo+/Vo- was accompanied by less recovery velocity of calcemia in the aluminum treated group, being indirectly related to the parathyroid gland response to calcium depletion. In the model that we studied the decreased bone turnover could have been caused by deposits of aluminum in bone; however there could exist associated factors such as dysfunction in the secretion of PTH, or less affinity between its receptors at the bone level.
- Published
- 1998
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