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1.
J Dairy Sci ; 107(5): 2916-2929, 2024 May.
Article in English | MEDLINE | ID: mdl-38101747

ABSTRACT

Dietary fat is fed to increase energy intake and provide fatty acids (FA) to support milk fat production. Oilseeds contain unsaturated FA that increase the risk for biohydrogenation-induced milk fat depression, but FA in whole cottonseed (WCS) are expected to be slowly released in the rumen and thus have a lower risk for biohydrogenation-induced milk fat depression. Our hypothesis was that increasing dietary WCS would increase milk fat yield by providing additional dietary FA without induction of milk fat depression. Four primiparous and 8 multiparous lactating Holstein cows, 136 ± 35 and 127 ± 4 DIM, respectively, were arranged in a replicated 4 × 4 Latin square design with 21-d periods. Treatments were WCS provided at 0%, 3.4%, 6.8%, and 9.9% of dietary dry matter, and WCS was substituted for cottonseed hulls and soybean meal to maintain dietary fiber and protein. Treatment did not change milk yield. There was a treatment-by-parity interaction for milk fat percent and yield with a quadratic decreased in primiparous cows but no effect of WCS in multiparous cows. Cottonseed linearly increased milk fat trans-10 18:1 in primiparous cows but not in multiparous cows. Increasing WCS increased milk preformed (18C) FA yield and partially overcame the trans-10 18:1 inhibition of de novo FA synthesis in the primiparous cows. Apparent transfer of 18C FA from feed to milk decreased in all cows as WCS increased, but the magnitude of the change was greater in primiparous cows. Increasing WCS decreased total-tract apparent dry matter, organic matter, and neutral detergent fiber digestibility. There was no change in total FA digestibility. However, 18C FA digestibility tended to be decreased in both parities and 16C FA digestibility was quadratically increased in multiparous cows but not changed in primiparous cows. Total fecal flow of intact WCS increased as WCS level increased, but fecal flow of intact seeds as a percentage consumed was similar across treatments. Fecal flow of intact seeds was greater in multiparous cows (4.3% vs. 1.1% of consumed). Plasma concentrations of glucose, nonesterified FA, triglycerides, and insulin were not changed. However, plasma urea-N increased with increasing WCS. Plasma gossypol increased with WCS (0.08-1.15 µg/mL) but was well below expected toxic levels. In conclusion, WCS maintained milk and milk component yield when fed at up to 9.9% of the diet to multiparous cows without concerns of gossypol toxicity, but primiparous cows were more susceptible to biohydrogenation-induced milk fat depression in the current trial. This highlights the interactions of parity with diet composition when feeding rumen-available unsaturated fat to dairy cows.


Subject(s)
Gossypol , Milk , Female , Cattle , Animals , Milk/metabolism , Fatty Acids/metabolism , Cottonseed Oil/metabolism , Lactation/physiology , Gossypol/metabolism , Gossypol/pharmacology , Digestion , Animal Feed/analysis , Diet/veterinary , Dietary Supplements/analysis , Rumen/metabolism
2.
J Intellect Disabil Res ; 64(7): 524-537, 2020 07.
Article in English | MEDLINE | ID: mdl-32329168

ABSTRACT

BACKGROUND: There is limited research quantifying the direct and indirect economic costs associated with intellectual disability (ID) in Australia. Costs incurred by families, governments and broader society include time spent providing care, absenteeism and increased healthcare utilisation. The purpose of this research is to quantify the costs associated with ID in childhood using a range of methods to collect cost data. METHODS: Costs included healthcare service utilisation, pharmaceutical use, caregiver productivity losses and time spent providing care because of the child's disability. The sample comprised caregivers with a child with ID aged between 2 and 10 years old recruited in Australia. Healthcare service utilisation and pharmaceutical use were obtained from routinely collected administrative claims data. Healthcare utilisation not captured in the routinely collected administrative data and absenteeism data were obtained from a retrospective recall-based questionnaire. Time spent providing care because of the child's disability was obtained using a time-use diary. RESULTS: The total cost of ID in Australia was estimated to be AUD 72 027 per year per child, and the total cost of ID in childhood was estimated to be AUD 12.5 billion per year. The cost to governments of ID in childhood was estimated to be AUD 6385 per child per year, resulting in a total cost to government of AUD 1.1 billion per year. CONCLUSIONS: This is the first study to estimate the direct and indirect costs associated with ID in childhood. The results of this research demonstrate the considerable economic impact of ID in childhood on families, governments and broader society in terms of both direct and indirect costs. An understanding of the cost implications of any intervention are critical in assisting policymakers in planning and prioritising of health services.


Subject(s)
Cost of Illness , Facilities and Services Utilization/economics , Health Care Costs/statistics & numerical data , Intellectual Disability/economics , Australia , Child , Child, Preschool , Female , Humans , Male , Retrospective Studies
3.
J Intellect Disabil Res ; 64(2): 103-116, 2020 02.
Article in English | MEDLINE | ID: mdl-31840365

ABSTRACT

BACKGROUND: Children with intellectual disability (ID) frequently have significant educational, social and health care needs, resulting in caregivers often experiencing a wide range of negative effects. This paper aims to determine the impact of childhood ID on caregivers' health-related quality of life (HRQoL) across co-morbid diagnostic groups. The second aim of this study is to determine the risk factors associated with lower HRQoL in this population. METHODS: Caregivers of a child with ID aged between 2 and 12 years old completed an online survey to determine their HRQoL using the EQ-5D-5L measure. They were also asked demographic questions and about their dependent child's level of behavioural and emotional difficulties. RESULTS: Of the total sample of 634 caregivers, 604 caregivers completed all five questions of the EQ-5D-5L. The mean age of caregivers was 39.1 years and 91% were women. Caregivers spent on average 66.6 h per week caring for their child related to their child's disability. The mean EQ-5D-5L score of caregivers was 0.80 (95% confidence interval: 0.79, 0.82), which is below the estimated Australian population norms (mean utility score of 0.92) for the age-equivalent population. Caregivers of children with autism spectrum disorders reported the lowest HRQoL (0.77, 95% confidence interval: 0.74, 0.79) of the five included co-morbid diagnostic groups. Caregivers with a lower income, a perceived low level of social support and children with higher degree of behavioural and emotional problems were likely to have a statistically lower HRQoL. CONCLUSIONS: This is the first study to produce utility values for caregivers of children with ID. The utility values can be used to compare health states and can be used to inform comparative cost-effectiveness analyses. Demonstrating that caregivers of children with ID have reduced HRQoL and that this is associated with the degree of behavioural and emotional problems has important policy implications, highlighting the potential for policy interventions that target behavioural and emotional problems to improve outcomes for caregivers.


Subject(s)
Autism Spectrum Disorder/nursing , Behavioral Symptoms/nursing , Caregivers/psychology , Disabled Children , Intellectual Disability/nursing , Parents/psychology , Quality of Life/psychology , Adult , Affective Symptoms/etiology , Affective Symptoms/nursing , Aged , Australia , Autism Spectrum Disorder/complications , Behavioral Symptoms/etiology , Child , Child, Preschool , Female , Grandparents/psychology , Humans , Intellectual Disability/complications , Male , Middle Aged , Young Adult
4.
Scand J Med Sci Sports ; 27(1): 35-44, 2017 Jan.
Article in English | MEDLINE | ID: mdl-26639349

ABSTRACT

Post-activation potentiation (PAP) is the increased involuntary muscle twitch response to stimulation following strong contraction. The enhancement to whole-body explosive muscular performance (PE) after heavy-resistance exercise is often attributed to modulations in neuromuscular function that are proposed to reflect PAP, but the evidence to support this is equivocal. We assessed the neuromuscular basis of PE using transcranial magnetic stimulation (TMS) of the primary motor cortex, and electrical stimulation of the femoral nerve. Eleven male athletes performed heavy-resistance exercise with measures of countermovement jump (CMJ) pre- and 8 min post-exercise. Pre-exercise and after the final CMJ, single- and paired-pulse TMS were delivered during submaximal isometric knee-extensor contractions to measure corticospinal excitability, short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF), with motor evoked potentials recorded from rectus femoris. Twitch responses to motor nerve stimulation during and post maximum-knee-extensor contractions were studied to quantify voluntary activation (VA) and potentiated twitch (Qtw,pot ). The experimental protocol successfully induced PE (+4 ± 1% change in CMJ, P = 0.01), but no changes were observed for maximum voluntary force, VA, corticospinal excitability, SICI or ICF (all P > 0.05), and Qtw,pot declined (P < 0.001). An enhancement of muscular performance after heavy-resistance exercise was not accompanied by PAP, or changes in measures of neuromuscular function.


Subject(s)
Athletic Performance/physiology , Evoked Potentials, Motor/physiology , Femoral Nerve/physiology , Motor Cortex/physiology , Neural Conduction/physiology , Quadriceps Muscle/physiology , Resistance Training , Action Potentials , Adult , Athletes , Electric Stimulation , Electromyography , Exercise/physiology , Humans , Isometric Contraction/physiology , Male , Neural Inhibition/physiology , Pyramidal Tracts/physiology , Transcranial Magnetic Stimulation , Young Adult
5.
Scand J Med Sci Sports ; 25 Suppl 1: 164-72, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25943667

ABSTRACT

The development of central fatigue is prominent following exercise-induced hyperthermia, but the contribution of supraspinal fatigue is not well understood. Seven endurance-trained cyclists (mean ± SD peak O2 uptake, 62.0 ± 5.6 mL/kg/min) completed two high-intensity constant-load cycling trials (296 ± 34 W) to the limit of tolerance in a hot (34 °C, 20% relative humidity) and, on a separate occasion, for the same duration, a control condition (18 °C, 20% relative humidity). Core body temperature (Tc ) was measured throughout. Before and immediately after each trial, twitch responses to supramaximal femoral nerve and transcranial magnetic stimulation were obtained from the knee extensors to assess neuromuscular and corticospinal function, respectively. Exercise time was 11.4 ± 2.6 min. Peak Tc was higher in the hot compared with control (38.36 ± 0.43 °C vs 37.86 ± 0.36 °C; P = 0.035). Post-exercise reductions in maximal voluntary contraction force (13 ± 9% vs 9 ± 5%), potentiated twitch force (16 ± 12% vs 21 ± 13%) and voluntary activation (9 ± 7% vs 7 ± 7%) were similar in hot and control trials, respectively. However, cortical voluntary activation declined more in the hot compared with the control (8 ± 3% vs 3 ± 2%; P = 0.001). Exercise-induced hyperthermia elicits significant central fatigue of which a large portion can be attributed to supraspinal fatigue. These data indicate that performance decrements in the heat might initially originate in the brain.


Subject(s)
Bicycling/physiology , Fatigue/physiopathology , Fever/physiopathology , Hot Temperature/adverse effects , Muscle Fatigue/physiology , Adult , Electric Stimulation , Electromyography , Exercise Test , Fatigue/etiology , Femoral Nerve/physiology , Fever/etiology , Humans , Male , Transcranial Magnetic Stimulation , Weight-Bearing
6.
Exp Physiol ; 94(9): 995-1004, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19561142

ABSTRACT

The aim of this study was to determine the applicability and reliability of a transcranial magnetic stimulation twitch interpolation technique for measuring voluntary activation of a lower limb muscle group. Cortical voluntary activation of the knee extensors was determined in nine healthy men on two separate visits by measuring superimposed twitch torques evoked by transcranial magnetic stimulation during isometric knee extensions of varying intensity. Superimposed twitch amplitude decreased linearly with increasing voluntary torque between 50 and 100% of mean maximal torque, allowing estimation of resting twitch amplitude and subsequent calculation of voluntary activation. There were no systematic differences for maximal voluntary activation within day (mean +/- s.d. 90.9 +/- 6.2 versus 90.7 +/- 5.9%; P = 0.98) or between days (90.8 +/- 6.0 versus 91.2 +/- 5.7%; P = 0.92). Systematic bias and random error components of the 95% limits of agreement were 0.23 and 9.3% within day versus 0.38 and 7.5% between days. Voluntary activation was also determined immediately after a 2 min maximal voluntary isometric contraction; in four of these subjects, voluntary activation was determined 30 min after the sustained contraction. Immediately after the sustained isometric contraction, maximal voluntary activation was reduced from 91.2 +/- 5.7 to 74.2 +/- 12.0% (P < 0.001), indicating supraspinal fatigue. After 30 min, voluntary activation had recovered to 85.4 +/- 8.8% (P = 0.39 versus baseline). These results demonstrate that transcranial magnetic stimulation enables reliable measurement of maximal voluntary activation and assessment of supraspinal fatigue of the knee extensors.


Subject(s)
Knee Joint/physiology , Muscle, Skeletal/physiology , Transcranial Magnetic Stimulation/methods , Adolescent , Adult , Electromyography , Evoked Potentials, Motor/physiology , Femoral Nerve/physiology , Humans , Isometric Contraction/physiology , Knee Joint/innervation , Male , Motor Cortex/physiology , Muscle, Skeletal/innervation , Young Adult
8.
Eur J Appl Physiol ; 105(4): 615-21, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19034491

ABSTRACT

The aim of this investigation was to elucidate the effects of cold water immersions (CWIs) following damaging exercise on the repeated bout effect (RBE). Sixteen males performed two bouts of drop jump exercise separated by 14-21 days. Participants were equally, but randomly assigned to either a CWI (12-min CWI at 15 degrees C) or control group (12-min seated rest). Treatments were given immediately after the first exercise bout, 24, 48 and 72 h post-exercise. No interventions were given following the second bout. Maximum voluntary contraction (MIVC), soreness (DOMS), creatine kinase (CK), thigh girth and range of motion (ROM) were recorded before and for 96 h following the initial and repeated bouts of damaging exercise. All variables, except ROM, showed a significant time effect (P < 0.01) indicating the presence of muscle damage following the initial bout; there were no differences between the CWI and control groups after the initial bout. Following the repeated bout of exercise there was a significant attenuation in the reduction of MIVC (P = 0.002) and a reduction in DOMS (P < 0.001), which is indicative of the RBE. There were no significant differences between groups following the repeated bout of damaging exercise. These data show that CWI had no effect following damaging exercise and did not inhibit the RBE. Despite CWI being used routinely, its efficacy remains unclear and there is a need to elucidate the benefits of this intervention on recovery and adaptation to provide practitioners with evidence based practice.


Subject(s)
Adaptation, Physiological/physiology , Cryotherapy , Exercise/physiology , Muscle, Skeletal/injuries , Adult , Cold Temperature , Creatine Kinase/metabolism , Electromyography , Humans , Male , Muscle Contraction/physiology , Muscle Relaxation/physiology , Muscle, Skeletal/physiology , Range of Motion, Articular/physiology
9.
Curr Oncol ; 26(3): e410-e413, 2019 06.
Article in English | MEDLINE | ID: mdl-31285686

ABSTRACT

Two guidelines about opioid use in chronic pain management were published in 2017: the Canadian Guideline for Opioids for Chronic Non-Cancer Pain and the European Pain Federation position paper on appropriate opioid use in chronic pain management. Though the target populations for the guidelines are the same, their recommendations differ depending on their purpose. The intent of the Canadian guideline is to reduce the incidence of serious adverse effects. Its goal was therefore to set limits on the use of opioids. In contrast, the European Pain Federation position paper is meant to promote safe and appropriate opioid use for chronic pain. The content of the two guidelines could have unintentional consequences on other populations that receive opioid therapy for symptom management, such as patients with cancer. In this article, we present expert opinion about those chronic pain management guidelines and their impact on patients with cancer diagnoses, especially those with histories of substance use disorder and psychiatric conditions. Though some principles of chronic pain management can be extrapolated, we recommend that guidelines for cancer pain management should be developed using empirical data primarily from patients with cancer who are receiving opioid therapy.


Subject(s)
Analgesics, Opioid/therapeutic use , Cancer Pain/drug therapy , Chronic Pain/drug therapy , Opioid-Related Disorders/prevention & control , Practice Guidelines as Topic , Analgesics, Opioid/adverse effects , Canada , Europe , Humans , Pain Management
10.
J Dairy Sci ; 91(1): 1-10, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18096919

ABSTRACT

Synthetic microporous membranes with functional groups covalently attached were used to selectively separate beta-lactoglobulin, BSA, and alpha-lactalbumin from rennet whey. The selectivity and membrane performance of strong (quaternary ammonium) and weak (diethylamine) ion-exchange membranes were studied using breakthrough curves, measurement of binding capacity, and protein composition of the elution fraction to determine the binding behavior of each membrane. When the weak and strong anion exchange membranes were saturated with whey, they were both selective primarily for beta-lactoglobulin with less than 1% of the eluate consisting of alpha-lactalbumin or BSA. The binding capacity of a pure beta-lactoglobulin solution was in excess of 1.5 mg/cm2 of membrane. This binding capacity was reduced to approximately 1.2 mg/cm2 when using a rennet whey solution (pH 6.4). This reduction in protein binding capacity can be explained by both the competitive effects of other whey proteins and the effect of ions present in whey. Using binary solution breakthrough curves and rennet whey breakthrough curves, it was shown that alpha-lactalbumin and BSA were displaced from the strong and weak anion exchange membranes by beta-lactoglobulin. Finally, the effect of ionic strength on the binding capacity of individual proteins for each membrane was determined by comparing model protein solutions in milk permeate (pH 6.4) and a 10 mM sodium phosphate buffer (pH 6.4). Binding capacities of beta-lactoglobulin, alpha-lactalbumin, and BSA in milk permeate were reduced by as much as 50%. This reduction in capacity coupled with the low binding capacity of current ion exchange membranes are 2 serious considerations for selectively separating complex and concentrated protein solutions.


Subject(s)
Lactalbumin/isolation & purification , Lactoglobulins/isolation & purification , Milk Proteins/chemistry , Serum Albumin, Bovine/isolation & purification , Animals , Anions , Cattle , Chromatography, Ion Exchange/methods , Food Technology , Ion Exchange , Whey Proteins
11.
Acta Physiol (Oxf) ; 220(4): 486-500, 2017 08.
Article in English | MEDLINE | ID: mdl-27981782

ABSTRACT

INTRODUCTION: An initial bout of eccentric exercise is known to protect against muscle damage following a repeated bout of the same exercise; however, the neuromuscular adaptations owing to this phenomenon are unknown. AIM: To determine whether neuromuscular disturbances are modulated following a repeated bout of eccentric exercise. METHODS: Following eccentric exercise performed with the elbow flexors, we measured maximal voluntary force, resting twitch force, muscle soreness, creatine kinase (CK) and voluntary activation (VA) using motor point and motor cortex stimulation at baseline, immediately post-exercise and at 1, 2, 3, 4 and 7 days post-exercise on two occasions, separated by 3 weeks. RESULTS: Significant muscle damage and fatigue were evident following the first exercise bout; maximal voluntary contraction (MVC) was reduced immediately by 35% and remained depressed at 7 days post-exercise. Soreness and CK release peaked at 3 and 4 days post-exercise respectively. Resting twitch force remained significantly reduced at 7 days (-48%), whilst VA measured with motor point and motor cortex stimulation was reduced until 2 and 3 days respectively. A repeated bout effect (RBE) was observed with attenuated soreness and CK release and a quicker recovery of MVC and resting twitch force. A similar decrement in VA was observed following both bouts; however, following the repeated bout there was a significantly smaller reduction in, and a faster recovery of, VA measured using motor cortical stimulation. CONCLUSION: Our data suggest that the RBE may be explained, partly, by a modification in motor corticospinal drive.


Subject(s)
Adaptation, Physiological/physiology , Exercise/physiology , Muscle, Skeletal/physiology , Electromyography , Humans , Male , Muscle Contraction/physiology , Myalgia , Young Adult
12.
Sci Rep ; 6: 19002, 2016 Jan 07.
Article in English | MEDLINE | ID: mdl-26740072

ABSTRACT

We study transverse electron momentum distribution in strong field atomic ionization driven by laser pulses with varying ellipticity. We show, both experimentally and theoretically, that the transverse electron momentum distribution in the tunneling and over the barrier ionization regimes evolves in a qualitatively different way when the ellipticity parameter describing polarization state of the driving laser pulse increases.

13.
Circulation ; 104(3): 304-9, 2001 Jul 17.
Article in English | MEDLINE | ID: mdl-11457749

ABSTRACT

BACKGROUND: Patients with abdominal aortic aneurysms (AAAs) exhibit arterial dilation and altered matrix composition throughout the vasculature. Matrix metalloproteinase-2 (MMP-2) is the dominant elastase in small AAAs, and overexpression of MMP-2 in vascular smooth muscle cells (SMCs) may be a primary etiological event in aneurysm genesis. The aim of this study was to investigate MMP-2 production in vascular tissue remote from the abdominal aorta. METHODS AND RESULTS: Inferior mesenteric vein (IMV) was harvested from patients undergoing aneurysm repair (n=21) or colectomy for diverticular disease (n=13, control). Matrix composition of the vessels was determined by stereological techniques. MMPs were extracted from tissue homogenates and quantified by gelatin zymography and ELISA. MMP-2, membrane type-1 MMP (MT1-MMP), and tissue inhibitor of metalloproteinases type 2 (TIMP-2) expression were determined by Northern analysis. SMCs were isolated from IMV, and the production and expression of MMP-2 and TIMP-2 in the SMC lines were quantified. Tissue homogenates and isolated inferior mesenteric SMCs from patients with aneurysms demonstrated significantly elevated MMP-2 levels, with no difference in TIMP-2 or MT1-MMP. These differences were a result of increased MMP-2 expression. Histological examination revealed fragmentation of elastin fibers within venous tissue obtained from patients with AAA and a significant depletion of the elastin within the media. In situ zymography localized elastolysis to medial SMCs. CONCLUSIONS: Patients with AAA have elevated MMP-2 levels in the vasculature remote from the aorta. This finding is due to increased MMP-2 expression from SMCs, a characteristic maintained in tissue culture. These data support both the systemic nature of aneurysmal disease and a primary role of MMP-2 in aneurysm formation.


Subject(s)
Aortic Aneurysm, Abdominal/enzymology , Matrix Metalloproteinase 2/metabolism , Mesenteric Veins/enzymology , Muscle, Smooth, Vascular/enzymology , Aged , Aged, 80 and over , Aortic Aneurysm, Abdominal/pathology , Aortic Aneurysm, Abdominal/surgery , Blotting, Northern , Cells, Cultured , Elastin/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunohistochemistry , Male , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinases, Membrane-Associated , Mesenteric Veins/cytology , Metalloendopeptidases/genetics , Metalloendopeptidases/metabolism , Middle Aged , Muscle, Smooth, Vascular/cytology , RNA, Messenger/analysis , Tissue Inhibitor of Metalloproteinase-2/genetics , Tissue Inhibitor of Metalloproteinase-2/metabolism
14.
Genetics ; 143(3): 1321-37, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8807304

ABSTRACT

The Scalloped wings (Scl) gene of the Australian sheep blowfly, Lucilia cuprina, is shown to be the homologue of the Drosophila melanogaster Notch gene by comparison at the DNA sequence and genetic levels. A L. cuprina genomic fragment, which shows strong identity with the Notch (N) gene at the molecular level, hybridizes to the location of the Scl gene on polytene chromosomes. The two genes are functionally homologous; the dominant and recessive Notch-like phenotypes produced by mutations in the Scl gene allow these alleles to be classed as N-like or Abruptex-like. The Scl gene is under investigation as a candidate for the fitness and asymmetry Modifier (M) of diazinon resistance. We show that M affects the penetrance of wing and bristle phenotypes associated with two Scl alleles in a manner consistent with the M being an allele of Scl. In addition, we report a phenotypic interaction between the diazinon-resistance mutation, Rop-1, and the same alleles of Scl. We propose that the product of Rop-1, an esterase, may be involved in cell adhesion in developmental processes involving the Scl gene product.


Subject(s)
Diazinon , Diptera/genetics , Drosophila Proteins , Insect Hormones/genetics , Insecticide Resistance/genetics , Insecticides , Membrane Proteins/genetics , Transcription Factors/genetics , Alleles , Amino Acid Sequence , Animals , Drosophila melanogaster/genetics , Homozygote , Molecular Sequence Data , Mutation , Phenotype , Receptors, Notch
15.
J Cereb Blood Flow Metab ; 18(9): 998-1007, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9740103

ABSTRACT

When a cerebral infarction occurs, surrounding the core of dying tissue there usually is an ischemic penumbra of nonfunctional but still viable tissue. One current but controversial hypothesis is that this penumbra tissue often eventually dies because of the metabolic stress imposed by multiple cortical spreading depression (CSD) waves, that is, by ischemic depolarizations. We describe here a computational model of CSD developed to study the implications of this hypothesis. After simulated infarction, the model displays the linear relation between final infarct size and the number of CSD waves traversing the penumbra that has been reported experimentally, although damage with each individual wave progresses nonlinearly with time. It successfully reproduces the experimental dependency of final infarct size on midpenumbra cerebral blood flow and potassium reuptake rates, and predicts a critical penumbra blood flow rate beyond which damage does not occur. The model reproduces the dependency of CSD wave propagation on N-methyl-D-aspartate activation. It also makes testable predictions about the number, velocity, and duration of ischemic CSD waves and predicts a positive correlation between the duration of elevated potassium in the infarct core and the number of CSD waves. These findings support the hypothesis that CSD waves play an important causal role in the death of ischemic penumbra tissue.


Subject(s)
Computer Simulation , Cortical Spreading Depression/physiology , Ischemic Attack, Transient/physiopathology , Models, Neurological , Cerebral Infarction/physiopathology , Linear Models
16.
Gene ; 289(1-2): 141-9, 2002 May 01.
Article in English | MEDLINE | ID: mdl-12036592

ABSTRACT

Three single copy ATP-binding cassette (ABC) transporter encoding genes, designated MgAtr3, MgAtr4, and MgAtr5, were cloned and sequenced from the plant pathogenic fungus Mycosphaerella graminicola. The encoded ABC proteins all exhibit the [NBD-TMS(6)](2) configuration and can be classified as novel members of the pleiotropic drug resistance (PDR) class of ABC transporters. The three proteins are highly homologous to other fungal and yeast, ABC proteins involved in multidrug resistance or plant pathogenesis. MgAtr4 and MgAtr5 possess a conserved ABC motif at both the N- and C-terminal domain of the protein. In contrast, the Walker A motif in the N-terminal and the ABC signature in the C-terminal domain of MgAtr3, deviate significantly from the consensus sequence found in other members of the PDR class of ABC transporters. Expression of MgAtr3 could not be detected under any of the conditions tested. However, MgAtr4 and MgAtr5 displayed distinct expression profiles when treated with a range of compounds known to be either substrates or inducers of ABC transporters. These included synthetic fungitoxic compounds, such as imazalil and cyproconazole, natural toxic compounds, such as the plant defence compounds eugenol and psoralen, and the antibiotics cycloheximide and neomycin. The expression pattern of the genes was also dependent on the morphological state of the fungus. The findings suggest a role for MgAtr4 and MgAtr5 during plant pathogenesis and in protection against toxic compounds.


Subject(s)
ATP-Binding Cassette Transporters/genetics , Ascomycota/genetics , Amino Acid Sequence , Ascomycota/drug effects , Cloning, Molecular , DNA, Fungal/chemistry , DNA, Fungal/genetics , Gene Expression Regulation, Fungal/drug effects , Molecular Sequence Data , Phylogeny , Protein Isoforms/genetics , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Triticum/microbiology , Xenobiotics/pharmacology
17.
Neuroreport ; 12(8): 1609-14, 2001 Jun 13.
Article in English | MEDLINE | ID: mdl-11409726

ABSTRACT

There is long-standing disagreement among experimentalists about whether transcallosal interhemispheric influences are primarily excitatory or inhibitory. Past computational models exploring this issue have encountered a similar dilemma: inhibitory callosal influences best explain hemispheric functional asymmetries, but excitatory callosal influences best explain transcallosal diaschisis. We recently hypothesized that this dilemma might be resolved by assuming excitatory callosal influences and a subcortical mechanism for cross-midline inhibition. Here we explore the feasibility of this hypothesis by examining a model of map formation in corresponding left and right cortical regions. The results show for the first time that both map asymmetries and diaschisis-like changes can be produced in a single model, suggesting that subcortical inhibitory processes may contribute more to asymmetric cortical functionality than is generally recognized.


Subject(s)
Cerebral Cortex/physiology , Corpus Callosum/physiology , Dominance, Cerebral/physiology , Models, Neurological , Brain Diseases/physiopathology , Brain Mapping , Cerebral Cortex/physiopathology , Corpus Callosum/physiopathology , Feasibility Studies , Humans , Neural Inhibition/physiology
18.
Neurol Res ; 23(5): 465-71, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11474802

ABSTRACT

It is often suggested that a major factor in diaschisis is the loss of transcallosal excitation to the intact hemisphere from the lesioned one. However, there is long-standing disagreement in the broader experimental literature about whether transcallosal interhemispheric influences in the human brain are primarily excitatory or inhibitory. Some experimental data are apparently better explained by assuming inhibitory callosal influences. Past neural network models attempting to explore this issue have encountered the same dilemma: in intact models, inhibitory callosal influences best explain strong cerebral lateralization like that occurring with language, but in lesioned models, excitatory callosal influences best explain experimentally observed hemispheric activation patterns following brain damage. We have now developed a single neural network model that can account for both types of data, i.e., both diaschisis and strong hemisphere specialization in the normal brain, by combining excitatory callosal influences with subcortical cross-midline inhibitory interactions. The results suggest that subcortical competitive processes may be a more important factor in cerebral specialization than is generally recognized.


Subject(s)
Cerebral Cortex/metabolism , Corpus Callosum/physiology , Functional Laterality/physiology , Neural Inhibition/physiology , Neural Networks, Computer , Neural Pathways/physiology , Neurons/physiology , Brain Injuries/metabolism , Brain Injuries/physiopathology , Cerebral Cortex/anatomy & histology , Cerebrovascular Circulation/physiology , Cortical Spreading Depression/physiology , Humans , Learning/physiology , Membrane Potentials/physiology , Synaptic Transmission/physiology , Verbal Behavior/physiology
19.
Blood Coagul Fibrinolysis ; 4(1): 159-64, 1993 Feb.
Article in English | MEDLINE | ID: mdl-8457646

ABSTRACT

Automated assays for the measurement of cross-linked fibrin derivatives in plasma (XL-FbDP) have been developed utilizing latex beads coated with anti-D dimer monoclonal antibody (DD-3B6/22) for both the Cobas Fara Chemistry Centrifugal and the Cobas Mira analysers (Roche, Basle, Switzerland). The analysers were programmed to mix plasma and latex reagent simultaneously and analyse absorbance changes over a 10-15 min period. Results were interpolated by the analyser from a standard curve derived from a polymer of D-dimer. Both assays had high precision (< 5% CV) for values between 100 and 1000 ng/ml and provided clear discrimination between normal samples and samples from patients suffering from the thrombotic diseases, DVT/PE and DIC. The results obtained for XL-FbDP determination with both methods compared well with established methods: a high correlation was obtained with a semi-quantitative manual latex method for both the Fara (r = 0.92) and Mira (r = 0.83) and correlations (r) of 0.81 (Fara) and 0.84 (Mira) were obtained with an enzyme immunoassay (EIA). Correlation between the two automated procedures was high (r = 0.96). The automated method will enable laboratories to provide a rapid and accurate quantitation of XL-FbDP.


Subject(s)
Fibrin Fibrinogen Degradation Products/analysis , Antibodies, Monoclonal , Automation , Blood Chemical Analysis/instrumentation , Blood Chemical Analysis/methods , Humans , Latex , Microspheres , Robotics
20.
Curr Eye Res ; 23(1): 51-9, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11821986

ABSTRACT

PURPOSE: To investigate the ex vivo wettability of Etafilcon A contact lenses over an eight hour period of wear and observe the influence of surfactant pre-treatment. METHODS: Etafilcon A hydrogel lenses, comprising poly[2-hydroxyethyl methacrylate-co-methacrylic acid] and 58% water, were soaked for 12 hours in either 0.9% saline (control) or a 1% aqueous solution of poloxamine 1107 (treated). The advancing and receding contact angles were subsequently determined ex vivo after various periods of wear in six adapted contact lens wearers using a single-blind, randomised protocol. Contact angles were measured with a dynamic contact angle tensiometer, using the Wilhelmy plate technique. Patient comfort scores were recorded and the static surface tensions of the probe fluids assessed. RESULTS: Control lenses exhibited no change in wetting angles over time, indicating a lack of surface modification by components within the tear film. Treated lenses exhibited a significantly reduced advancing angle (p < 0.001) and hysteresis angle (p < 0.001) when compared with control lenses. In addition, treated lenses were consistently rated as being more comfortable than control lenses (p = 0.04). CONCLUSIONS: This study has shown clearly that new Etafilcon A lenses do not exhibit significant changes in wettability during the initial four hour wearing period. Pre-treatment of such lenses with a polymeric surfactant results in wetting of the lenses due to the adsorption of surfactant. The surfactant is retained by the lens for at least eight hours of wear, resulting in significant improvements in subjective comfort, especially over the first 30 minutes of wear.


Subject(s)
Contact Lenses, Hydrophilic , Wettability , Adolescent , Adult , Ethylenediamines/pharmacology , Female , Humans , Male , Methacrylates , Middle Aged , Polyhydroxyethyl Methacrylate , Prosthesis Fitting , Sodium Chloride/pharmacology , Surface Tension
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