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1.
Mult Scler ; 27(12): 1894-1901, 2021 10.
Article in English | MEDLINE | ID: mdl-34197237

ABSTRACT

BACKGROUND: Vascular comorbidities (VCs) including hypertension (HTN) are associated with worse multiple sclerosis (MS) outcomes. HTN is common in Latinx, but the prevalence and relationship with disability are unknown in Latinx with MS. METHODS: Latinx (n = 451) from the Alliance for Research in Hispanic MS (ARHMS) seen between 2007 and 2019 were included. HTN, diabetes (DM), hyperlipidemia (HLD), ischemic events, and smoking were considered VC. Blood pressures (BPs) were classified using the American Heart Association (AHA) criteria. Logistic regression determined associations between VC and ambulatory disability accounting for age, sex, and disease duration. RESULTS: Medical comorbidities were found in 41.9% and VC in 24.2%. Smoking (13.6%) and HTN (7.3%) were the most common. HTN was the most common over the age of 40 (12.6%). The odds of having severe disability were three times higher for those with HTN (odds ratio [OR], 3.12; 95% confidence interval (CI), 1.37-7.12). Stage II HTN according to AHA also tripled the odds (OR, 2.89; 95%CI, 1.11-7.55). AHA BP confirmed HTN in 27.5% (compared to 7.3% with established diagnosis). CONCLUSION: HTN diagnosis and stage II HTN defined by AHA were independently associated with severe ambulatory disability in Latinx with MS. HTN was underdiagnosed. Future studies should assess whether HTN treatment control would prevent disability in MS.


Subject(s)
Hypertension , Multiple Sclerosis , Hispanic or Latino , Humans , Hypertension/epidemiology , Multiple Sclerosis/epidemiology , Odds Ratio , Prevalence
2.
Can J Physiol Pharmacol ; 90(5): 567-78, 2012 May.
Article in English | MEDLINE | ID: mdl-22471993

ABSTRACT

In this study, we hypothesized that athletes involved in 5-6 months of sprint-type training would display higher levels of proteins and processes involved in muscle energy supply and utilization. Tissue was sampled from the vastus lateralis of 13 elite ice hockey players (peak oxygen consumption = 51.8 ± 1.3 mL·kg(-1)·min(-1); mean ± standard error) at the end of a season (POST) and compared with samples from 8 controls (peak oxygen consumption = 45.5 ± 1.4 mL·kg(-1)·min(-1)) (CON). Compared with CON, higher activities were observed in POST (p < 0.05) only for succinic dehydrogenase (3.32 ± 0.16 mol·(mg protein)(-1)·min(-1) vs. 4.10 ± 0.11 mol·(mg protein)(-1)·min(-1)) and hexokinase (0.73 ± 0.05 mol·(mg protein)(-1)·min(-1) vs. 0.90 ± 0.05mol·(mg protein)(-1)·min(-1)) but not for phosphorylase, phosphofructokinase, and creatine phosphokinase. No differences were found in Na(+),K(+)-ATPase concentration (ß(max): 262 ± 36 pmol·(g wet weight)(-1) vs. 275 ± 27 pmol·(g wet weight)(-1)) and the maximal activity of the sarcoplasmic reticulum Ca(2+)-ATPase (98.1 ± 6.1 µmol·(g protein)(-1)·min(-1) vs. 102 ± 3.3 µmol·(g protein)(-1)·min(-1)). Cross-sectional area was lower (p < 0.05) in POST but only for the type IIA fibres (6312 ± 684 µm(2) vs. 5512 ± 335 µm(2)), while the number of capillary counts per fibre and the capillary to fibre area ratio were generally higher (p < 0.05). These findings suggest that elite trained ice hockey players display elevations only in support of glucose-based aerobic metabolism that occur in the absence of alterations in excitation-contraction processes.


Subject(s)
Athletic Injuries/metabolism , Athletic Injuries/pathology , Cumulative Trauma Disorders/metabolism , Cumulative Trauma Disorders/pathology , Hockey , Sarcoplasmic Reticulum/metabolism , Sarcoplasmic Reticulum/pathology , Adult , Creatine Kinase/metabolism , Energy Metabolism , Glucose/metabolism , Hexokinase/metabolism , Humans , Musculoskeletal Physiological Phenomena , Oxygen Consumption/physiology , Phosphofructokinases/metabolism , Phosphorylases/metabolism , Quadriceps Muscle/metabolism , Quadriceps Muscle/physiology , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism , Sodium-Potassium-Exchanging ATPase/metabolism , Succinate Dehydrogenase/metabolism , Teaching/methods , Young Adult
3.
Appl Physiol Nutr Metab ; 35(5): 657-70, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20962922

ABSTRACT

We hypothesized that a season of ice hockey would result in extensive remodeling of muscle. Tissue sampled from the vastus lateralis of 15 players (age = 20.6 ± 0.4 years; mean ± SE) prior to (PRE) and following (POST) a season was used to characterize specific adaptations. Measurement of representative metabolic pathway enzymes indicated higher maximal activities in POST than in PRE (p < 0.05) for succinic dehydrogenase (3.26 ± 0.31 vs. 3.91 ± 0.11 mol mg protein(-1) min(-1)), citrate synthase (7.26 ± 0.70 vs. 8.70 ± 0.55 mol mg protein(-1) min(-1)), and phosphofructokinase (12.8 ± 1.3 vs. 14.4 ± 0.96 mol mg protein(-1) min(-1)) only. The season resulted in an increase in Na+-K+-ATPase concentration (253 ± 6.3 vs. 265 ± 6.0 pmol g(-1) wet weight), a decrease (p < 0.05) in maximal activity of the sarcoplasmic reticulum Ca2+-ATPase (107 ± 4.2 micromol g protein(-1) min(-1) vs. 92.0 ± 4.6 micromol g protein(-1) min(-1)), and no change in the distribution (%) of fibre types. A smaller (p < 0.05) cross-sectional area (CSA) for both type I (-11.7%) and type IIA (-18.2%) fibres and a higher (p < 0.05) capillary count/CSA for type I (+17.9%) and type IIA (+17.2%) were also found over the season. No changes were found in peak oxygen consumption (51.4 ± 1.2 mL kg(-1) min(-1) vs. 52.3 ± 1.3 mL kg(-1) min(-1)). The results suggest, based on the alterations in oxidative and perfusion potentials and muscle mass, that the dominant adaptations are in support of oxidative metabolism, which occurs at the expense of fibre CSA and possibly force-generating potential.


Subject(s)
Adaptation, Physiological/physiology , Energy Metabolism/physiology , Hockey/physiology , Muscle, Skeletal/cytology , Muscle, Skeletal/physiology , Adult , Calcium-Transporting ATPases/metabolism , Citrate (si)-Synthase/metabolism , Exercise/physiology , Humans , Male , Muscle Fibers, Skeletal/enzymology , Muscle Proteins/metabolism , Oxygen Consumption/physiology , Phosphofructokinase-1, Muscle Type/metabolism , Sodium-Potassium-Exchanging ATPase/metabolism , Succinate Dehydrogenase/metabolism
4.
Int J Gen Med ; 2: 227-42, 2009 Dec 29.
Article in English | MEDLINE | ID: mdl-20360908

ABSTRACT

The objective of this paper is to provide an overview of the recent developments in muscle physiology and biochemistry in general, and with respect to chronic obstructive pulmonary disease (COPD) specifically. As a way of illustration, we have presented data on the remodeling that occurs in vastus lateralis in two patients with COPD (COPD #1, forced expiratory volume in one second/forced vital capacity [FEV(1)/FVC] = 63%; COPD #2, FEV(1)/FVC = 41%) exhibiting differences in muscle wasting as compared to healthy controls (CON; FEV(1)/FVC = 111 +/- 2.2%, n = 4). Type I fibers percentages were lower in both COPD #1 (16.7) and COPD #2 (24.9) compared to CON (57.3 +/- 5.2). Cross sectional area of the type I fibers of the patients ranged between 65%-68% of CON and for the type II subtypes (IIA, IIAX, IIX) between 74% and 89% (COPD #1) and 17%-32% (COPD #2). A lower number of capillary contacts were observed for all fiber types in COPD #1 but not COPD #2. Lower concentrations of adenosine triphosphate (ATP) (24%-26%) and phosphocreatine (18%-20%), but not lactate occurred in COPD. In contrast to COPD #1, who displayed normal glucose transporter content, GLUT1 and GLUT4 were only 71% and 54%, respectively of CON in COPD #2. Lower monocarboxylate contents were found for MCT1 in both COPD #1 (63%) and COPD #2 (41%) and for MCT4 (78%) in COPD #1. Maximal oxidative enzyme activities (V(max)) for COPD #2 ranged between 37% (succinic dehydrogenase) and 70% (cytochrome C oxidase) of CON. For the cytosolic enzymes, V(max) ranged between 89% (hexokinase) to 31% (pyruvate kinase) of CON. Depressions were also observed in V(max) of the Na(+)-K(+)-ATPase for COPD #1 (66% of CON) but not COPD #2 (92% of CON) while V(max) of the Ca(2+)-ATPase was near normal in COPD #1 (84% CON). It is concluded that disturbances can occur in muscle to a wide range of excitation, contraction and metabolic processes in COPD.

5.
Neurosurg Focus ; 23(4): E3, 2007.
Article in English | MEDLINE | ID: mdl-17961040

ABSTRACT

The histological appearance of a meningioma is an important predictor of tumor behavior and is frequently a factor in decisions concerning therapy. The relationship between histological features and prognosis is formalized in grading schemes such as those published by the World Health Organization (WHO), most recently in 2007. Although the latest edition is an improvement over previous grading schemes, the WHO scheme still fails to fully address a variety of important issues regarding the relationship between meningioma histological characteristics and behavior. In particular, routine histological examination fails to identify the subset of Grade I tumors that behave aggressively. Because of this, many additional prognostic markers that require immunohistochemical, cytogenetic, or molecular techniques to evaluate are under investigation. Only one, immunohistochemistry for the proliferation marker, Ki 67 (MIB-1), is used routinely and it has only limited utility. It is hoped that an understanding of the genetic changes that underlie tumor progression will improve healthcare professionals' ability to predict the behavior of meningiomas.


Subject(s)
Meningeal Neoplasms/pathology , Meningioma/pathology , Anaplasia/pathology , Antibodies, Antinuclear/metabolism , Antibodies, Monoclonal/metabolism , Humans , Meningeal Neoplasms/genetics , Meningeal Neoplasms/metabolism , Meningioma/genetics , Meningioma/metabolism , Neoplasm Invasiveness
6.
J Neurosci Res ; 84(6): 1225-34, 2006 Nov 01.
Article in English | MEDLINE | ID: mdl-16955483

ABSTRACT

Agonists of liver X receptors (LXR), members of the nuclear hormone receptor superfamily, alter secretion of proinflammatory cytokines, suggesting potential antiinflammatory effects. A synthetic LXR agonist inhibited T-cell proliferation and cytokine release in a dose-dependent manner. Treatment of mice during induction of experimental autoimmune encephalomyelitis reduced clinical symptoms, central nervous system cellular inflammation, and major histocompatibility class II expression on microglia, as well as demyelination. In contrast to in vitro analysis, no reductions in peripheral neuroantigen specific T-cell responses were detected in comparing ligand and vehicle treated mice. These data suggest that LXR agonists play an important protective role in the regulation of T-cell-mediated inflammatory disease of the central nervous system.


Subject(s)
DNA-Binding Proteins/agonists , Encephalomyelitis, Autoimmune, Experimental/pathology , Encephalomyelitis, Autoimmune, Experimental/prevention & control , Receptors, Cytoplasmic and Nuclear/agonists , Animals , CD4 Antigens/metabolism , Dose-Response Relationship, Drug , Female , Flow Cytometry , Gene Expression/drug effects , Genes, MHC Class II/genetics , Hydrocarbons, Fluorinated , Ligands , Liver X Receptors , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Orphan Nuclear Receptors , Ovalbumin/immunology , Ovalbumin/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sulfonamides/pharmacology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology
7.
Ann Neurol ; 60(1): 56-64, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16685699

ABSTRACT

OBJECTIVE: To address the inconsistency in the reported concordance of multiple sclerosis (MS) among twins by zygosity, sex, and latitude. METHODS: Four hundred eighteen medically documented monozygotic (MZ) and 380 same-sex dizygotic (DZ) pairs were ascertained from 1980 to 1992 and followed. The study population was representative of twins with multiple sclerosis. Twins from Canada and adjacent US states (at or above 41-42 degrees N) were considered "northern," and ancestry was dichotomized from descent from high-risk populations. Diagnosis before median age 29.3 years was considered "early." RESULTS: The MZ/DZ concordance ratio was 2.9 (95% confidence interval [CI], 1.0-8.9) among men and 2.6 (95% CI, 1.5-4.5) among women. The average age at northern diagnosis was independent of ancestry and 2 years earlier for both MZ (p < 0.02) and DZ (p < 0.01) patients. Among DZ twins, concordance was independent of all characteristics. Among MZ twins, concordance was 1.9 times (95% CI, 1.2-3.2) greater among northern twins, 1.9 (95% CI, 1.1-3.6) times greater among twins with high-risk ancestry, and 2.1 (95% CI, 1.2-3.6) times greater if diagnosis was early. Ancestry and early diagnosis made independent significant contributions to the differential concordance by latitude. INTERPRETATION: Multiple sclerosis is similarly heritable by sex, and the apparent variation in MZ concordance by latitude is influenced by environmental and genetic factors.


Subject(s)
Multiple Sclerosis/ethnology , Multiple Sclerosis/genetics , Adult , Age of Onset , Canada/epidemiology , Diagnostic Errors , Female , Humans , Male , Multiple Sclerosis/diagnosis , Risk Factors , Sex Distribution , Twins, Dizygotic , Twins, Monozygotic , United States/epidemiology
8.
J Neuroimmunol ; 155(1-2): 161-71, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15342208

ABSTRACT

Multiple Sclerosis (MS) is a chronic inflammatory disease of the CNS which is characterized by large mononuclear cell infiltration and significant demyelination. CXCL8 is a chemo-attractant for both neutrophils and monocytes and triggers their firm adhesion to endothelium. In this study, we demonstrate that serum CXCL8 and CXCL8 secretion from PBMCs are significantly higher in untreated MS patients compared to controls and are significantly reduced in MS patients receiving interferon-beta1a therapy. We suggest that CXCL8 may serve as a marker of monocyte activity in MS and may play a role in monocyte recruitment to the CNS.


Subject(s)
Chemokines, CXC/blood , Chemokines, CXC/immunology , Chemotaxis, Leukocyte/immunology , Intercellular Signaling Peptides and Proteins/blood , Intercellular Signaling Peptides and Proteins/immunology , Monocytes/immunology , Multiple Sclerosis/blood , Multiple Sclerosis/immunology , Adult , Aged , Biomarkers/blood , Central Nervous System/immunology , Central Nervous System/physiopathology , Chemokines, CXC/metabolism , Chemotaxis, Leukocyte/drug effects , Female , Humans , Intercellular Signaling Peptides and Proteins/metabolism , Interferon beta-1a , Interferon-beta/pharmacology , Interferon-beta/therapeutic use , Male , Middle Aged , Monocytes/drug effects , Multiple Sclerosis/drug therapy , Neutrophils/drug effects , Neutrophils/immunology , Predictive Value of Tests , Up-Regulation/drug effects , Up-Regulation/immunology
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