Biomedical subjects

M Christine Rodriguez

Publications and source records attributed to M Christine Rodriguez.

5 recordsLinked to original sources

PubMed2007

Beneficial effects of creatine, CoQ10, and lipoic acid in mitochondrial disorders.

Mitochondrial disorders share common cellular consequences: (1) decreased ATP production; (2) increased reliance on alternative anaerobic energy sources; and (3) increased production of reactive oxygen species. The purpose of the present study was to determine the effect of a combination therapy (creatine monohydrate, coenzyme Q(10), and lipoic acid to target the above-mentioned cellular consequences) on several outcome variables using a randomized, double-blind, placebo-controlled, crossover study design in patients with mitochondrial cytopathies. Three patients had mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), four had mitochondrial DNA deletions (three patients with chronic progressive external ophthalmoplegia and one with Kearns-Sayre syndrome), and nine had a variety of other mitochondrial diseases not falling into the two former groups. The combination therapy resulted in lower resting plasma lactate and urinary 8-isoprostanes, as well as attenuation of the decline in peak ankle dorsiflexion strength in all patient groups, whereas higher fat-free mass was observed only in the MELAS group. Together, these results suggest that combination therapies targeting multiple final common pathways of mitochondrial dysfunction favorably influence surrogate markers of cellular energy dysfunction. Future studies with larger sample sizes in relatively homogeneous groups will be required to determine whether such combination therapies influence function and quality of life.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2006

Nutritional therapy improves function and complements corticosteroid intervention in mdx mice.

Corticosteroid therapy for Duchenne muscular dystrophy is effective but associated with long-term side effects. To determine the potential therapeutic benefit from four nutritional compounds (creatine monohydrate, conjugated linoleic acid, alpha-lipoic acid, and beta-hydroxy-beta-methylbutyrate) alone, in combination, and with corticosteroids (prednisolone), we evaluated the effects on several variables in exercising mdx mice. Outcome measures included grip strength, rotarod performance, serum creatine kinase levels, muscle metabolites, internalized myonuclei, and retroperitoneal fat pad weight. In isolation, each nutritional treatment showed some benefit, with the combination therapy showing the most consistent benefits. Prednisolone and the combination therapy together provided the most consistent evidence of efficacy; increased peak grip strength (P < 0.05), decreased grip strength fatigue (P < 0.05), decreased number of internalized myonuclei (P < 0.01), and smaller retroperitoneal fat pad stores (P < 0.001). This study provided evidence for therapeutic benefit from a four-compound combination therapy alone, and in conjunction with corticosteroids in the mdx model of DMD.

Animals↗

PubMed2005

Caloric restriction transiently improves motor performance but hastens clinical onset of disease in the Cu/Zn-superoxide dismutase mutant G93A mouse.

Caloric restriction (CR) prolongs lifespan in insects, rodents, and nonhuman primates, a process attributed to a reduction in oxidative stress. Transgenic mice that overexpress the mutant human Cu/Zn-superoxide dismutase (SOD1) gene (G93A mice) are an animal model of amyotrophic lateral sclerosis showing progressively lower motor neuron weakness and increased oxidative stress. We investigated the effect of CR on motor performance, clinical onset, disease progression, and lifespan in G93A mice. Starting at 40 days of age, 14 separately caged G93A mice were randomly divided into two groups: ad libitum (AL; n = 6) and calorie-restricted (CR; n = 8) with a diet equal to 60% of AL. The CR mice (mean +/- SEM: 14.0 +/- 0.7 g) weighed 31% less than the AL mice (20.3 +/- 1.0 g) (P = 0.0002). From 74 to 93 days of age, the CR mice performed better on the rotarod than the AL mice: fall time, P = 0.039; fall speed, P = 0.009. The CR mice had a faster rate of reaching clinical onset than the AL mice (hazard ratio = 4.3, P = 0.0006). The CR and AL mice reached clinical onset of disease at age 99 +/- 1 and 110 +/- 2 days, respectively (P = 0.0003), with no significant difference in disease progression. The CR mice tended to reach endpoint sooner than the AL mice (age-specific death: 125 +/- 3 vs. 133 +/- 3 days, respectively, P = 0.09). We conclude that CR diet transiently improves motor performance but hastens clinical onset of disease in G93A mice. These results suggest that CR diet is not a protective strategy for patients with amyotrophic lateral sclerosis (ALS) and hence is contraindicated.

Amyotrophic Lateral Sclerosis↗

PubMed2003

Patients with dystrophinopathy show evidence of increased oxidative stress.

Duchenne muscular dystrophy (DMD) is associated with an increase in oxidative stress. We measured 24 h 8-hydroxy-2'-deoxyguanosine (8-OHdG) excretion in 24 patients with MD (DMD + Becker's MD), 23 with myotonic dystrophy, and 34 healthy controls. The 8-OHdG/creatinine ratio was higher in patients with dystrophinopathy ( upward arrow 48%, p <.01) but not myotonic dystrophy, as compared to healthy controls. These results indicate that 8-OHdG excretion can be used as a marker of oxidative stress in clinical trials with dystrophinopathy.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2003

Plasma malondialdehyde increases transiently after ischemic forearm exercise.

UNLABELLED: Exercise and ischemia-reperfusion (I-R) have previously been shown to induce oxidative stress in skeletal muscle. Previous studies have demonstrated conflicting results when exercise-induced oxidative stress has been measured using plasma carbonyls, specifically malondialdehyde (MDA). These conflicting results likely stem from the timing and method utilized to measure plasma carbonyls. PURPOSE: To determine the concentration and timing of aldehyde and ketone generation after ischemic forearm exercise utilizing HPLC analysis. METHODS: Plasma carbonyls, including MDA, 17-beta-estradiol, and lactate, were measured after a forearm ischemic exercise test (FIT) in males and females (in both phases of their menstrual cycle). Blood flow was occluded to the forearm, and six cycles of maximal isometric handgrip exercise were executed using a 9:1, duty:rest cycle, for 60 s. Blood samples were collected pre, immediately post, and 1, 3, and 10 min post-FIT. RESULTS: Plasma MDA increased similarly for both males and females immediately post and 1 min post-FIT (P<0.05) and returned to baseline levels by 3 min post-FIT. Ischemic exercise did not alter plasma concentrations of other measured carbonyls, and gender and menstrual cycle did not influence any measured variable (P>0.05), except for lactate concentrations, which increased more for males (P<0.05). Force was higher for males at all time points (P<0.05); however, there was no effect of gender on percent fatigue. CONCLUSIONS: Future studies must consider sampling times after metabolic stress in order to quantify changes in MDA concentration.

Adult↗