Biomedical subjects

Douglas W Theriaque

Publications and source records attributed to Douglas W Theriaque.

At least 19 recordsLinked to original sources

PubMed2006

Therapeutic potential of dichloroacetate for pyruvate dehydrogenase complex deficiency.

We reviewed the use of oral dichloroacetate (DCA) in the treatment of children with congenital lactic acidosis caused by mutations in the pyruvate dehydrogenase complex (PDC). The case histories of 46 subjects were analyzed with regard to diagnosis, clinical presentation and response to DCA. DCA decreased blood and cerebrospinal fluid lactate concentrations, and was generally well tolerated. DCA may be particularly effective in children with PDC deficiency by stimulating residual enzyme activity and, consequently, cellular energy metabolism. A controlled trial is needed to determine the definitive role of DCA in the management of this devastating disease.

Acidosis, Lactic↗

PubMed2006

Short-term atorvastatin treatment enhances specific antibody production following tetanus toxoid vaccination in healthy volunteers.

Statins possess anti-inflammatory and immunomodulatory properties beyond their cholesterol-lowering effects. To determine whether short-term atorvastatin treatment affects the acute phase and humoral immune responses to tetanus toxoid (TT) in normal healthy volunteers, we conducted a randomized, double blind, placebo-controlled trial. Twenty healthy volunteers were assigned a 10-day treatment with atorvastatin (40 mg) or placebo. All volunteers received a TT booster on the fifth day. Subjects in the atorvastatin group had a significant reduction in total and low-density lipoprotein cholesterol (both p<0.001). Unexpectedly, the production of anti-TT antibodies (predominately IgG1) was three-fold higher in the atorvastatin group 15 days post-vaccination (2306 +/- 468 versus 713+/-21 units, p = 0.008). Atorvastatin also suppressed the post-vaccination rise in platelet and lymphocyte counts (both p<0.05). Acute phase parameters did not change significantly in either group. This study illustrates a novel immunomodulatory effect of atorvastatin raising the possibility of using HMG-CoA reductase inhibitors to enhance humoral responses to vaccination.

Acute-Phase Proteins↗

PubMed2006

Neurocognitive findings in Prader-Willi syndrome and early-onset morbid obesity.

OBJECTIVES: To examine whether early-onset morbid obesity is associated with cognitive impairment, neuropathologic changes, and behavioral problems. STUDY DESIGN: This case-control study compared head MRI scans and cognitive, achievement, and behavioral evaluations of subjects with Prader-Willi syndrome (PWS), early-onset morbid obesity (EMO), and normal-weight sibling control subjects from both groups. Head MRI was done on 17 PWS, 18 EMO, and 21 siblings, and cognitive, achievement, and behavioral evaluations were done on 19 PWS, 17 EMO, and 24 siblings. RESULTS: The mean General Intellectual Ability score of the EMO group was 77.4 +/- 17.8; PWS, 63.3 +/- 14.2; and control subjects, 106.4 +/- 13.0. Achievement scores for the three groups were EMO, 78.7 +/- 18.8; PWS, 71.2 +/- 17.0; and control subjects, 104.8 +/- 17.0. Significant negative behaviors and poor adaptive skills were found in the EMO group. White matter lesions were noted on brain MRI in 6 subjects with PWS and 5 with EMO. None of the normal-weight control subjects had these findings. CONCLUSIONS: Individuals with EMO have significantly lower cognitive function and more behavioral problems than control subjects with no history of childhood obesity. Both EMO and PWS subjects have white matter lesions on brain MRI that have not previously been described.

Achievement↗

PubMed2006

Peripheral neuropathy in genetic mitochondrial diseases.

Peripheral neuropathy is an underrecognized but common occurrence in genetic mitochondrial disorders. To gain insight into the frequency and clinical presentation of this complication, nerve conduction studies were performed on 43 subjects with congenital lactic acidosis enrolled in a controlled clinical trial of oral dichloroacetate. Median and peroneal motor conduction studies and median and sural sensory conduction studies were performed on each patient. The mean amplitude of the peroneal motor nerve (P < 0.001) and the conduction velocities of the median (P < 0.001) and peroneal (P < 0.001) motor nerves were uniformly lower in our subjects than in healthy literature control subjects. There were no significant differences in sensory nerve conduction studies. A generalized reduction in motor nerve conduction velocity was the dominant electrophysiological abnormality in the patients in this study and was independent of age, sex, or congenital mitochondrial disorder. We postulate that cellular energy failure is the most likely common cause of peripheral neuropathy in patients with genetic mitochondrial diseases, owing to the high demand for adenosine triphosphate via aerobic carbohydrate metabolism by nerve tissue.

Acidosis, Lactic↗

PubMed2006

Assessing the relationship between preterm delivery and various microorganisms recovered from the lower genital tract.

OBJECTIVE: To determine if the likelihood of preterm delivery is more dependent on the specific organisms present in the vagina than on the presence of bacterial vaginosis. METHODS: We evaluated the vaginal fluid of a prospective cohort of women at 23-32 weeks of gestation with signs and symptoms of preterm labor and intact membranes. Forward stepwise logistic regression models were used to evaluate the relationship between preterm delivery and the presence of anaerobic bacteria, Gardnerella, ureaplasmas and mycoplasmas, and sialidase. RESULTS: The cohort included 137 women, and complete delivery information was available for 134 of them. The rate of preterm delivery was 28% (37 of 134). Mycoplasma genitalium independently was associated with spontaneous preterm delivery (OR 3.48; 95% CI 1.41, 8.57). After controlling for this factor, none of the other variables were significantly prognostic for spontaneous preterm delivery (residual overall p = 0.19). CONCLUSION: The presence of Mycoplasma genitalium in the vagina of pregnant women is an independent risk factor for spontaneous preterm delivery.

Adult↗

PubMed2006

Ambulatory continuous interscalene nerve blocks decrease the time to discharge readiness after total shoulder arthroplasty: a randomized, triple-masked, placebo-controlled study.

BACKGROUND: A continuous interscalene nerve block (CISB) may be used to provide analgesia after shoulder arthroplasty. Therefore, inpatient stays may be shortened if CISB (1) provides adequate analgesia without intravenous opioids and (2) improves shoulder mobilization. This study investigated the relationship between ambulatory CISB and the time to reach three discharge criteria after shoulder arthroplasty. METHODS: Preoperatively, patients received a CISB. All patients received a perineural 0.2% ropivacaine infusion from surgery until 06:00 the following morning, at which time they were randomly assigned either to continue perineural ropivacaine or to switch to normal saline. The primary endpoint was the time from the end of surgery until three discharge criteria were attained (adequate analgesia, independence from intravenous analgesics, and tolerance to 50% of shoulder motion targets). Patients were discharged home as early as the afternoon after surgery with their CISB using a portable infusion pump. RESULTS: Patients receiving perineural ropivacaine (n = 16) attained all three discharge criteria in a median (10th-90th percentiles) of 21 (16-41) h, compared with 51 (37-90) h for those receiving perineural normal saline (n = 13, P < 0.001). Unlike patients receiving perineural ropivacaine, patients receiving perineural normal saline often required intravenous morphine, but still experienced a higher degree of pain and tolerated less external rotation. CONCLUSIONS: An ambulatory CISB considerably decreases the time until readiness for discharge after shoulder arthroplasty, primarily by providing potent analgesia that permits greater passive shoulder movement and the avoidance of intravenous opioids. Additional research is required to define the appropriate subset of patients and assess the incidence of complications associated with earlier discharge.

Aged↗

PubMed2006

Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children.

OBJECTIVE: Open-label studies indicate that oral dichloroacetate (DCA) may be effective in treating patients with congenital lactic acidosis. We tested this hypothesis by conducting the first double-blind, randomized, control trial of DCA in this disease. METHODS: Forty-three patients who ranged in age from 0.9 to 19 years were enrolled. All patients had persistent or intermittent hyperlactatemia, and most had severe psychomotor delay. Eleven patients had pyruvate dehydrogenase deficiency, 25 patients had 1 or more defects in enzymes of the respiratory chain, and 7 patients had a mutation in mitochondrial DNA. Patients were preconditioned on placebo for 6 months and then were randomly assigned to receive an additional 6 months of placebo or DCA, at a dose of 12.5 mg/kg every 12 hours. The primary outcome results were (1) a Global Assessment of Treatment Efficacy, which incorporated tests of neuromuscular and behavioral function and quality of life; (2) linear growth; (3) blood lactate concentration in the fasted state and after a carbohydrate meal; (4) frequency and severity of intercurrent illnesses and hospitalizations; and (5) safety, including tests of liver and peripheral nerve function. OUTCOME: There were no significant differences in Global Assessment of Treatment Efficacy scores, linear growth, or the frequency or severity of intercurrent illnesses. DCA significantly decreased the rise in blood lactate caused by carbohydrate feeding. Chronic DCA administration was associated with a fall in plasma clearance of the drug and with a rise in the urinary excretion of the tyrosine catabolite maleylacetone and the heme precursor delta-aminolevulinate. CONCLUSIONS: In this highly heterogeneous population of children with congenital lactic acidosis, oral DCA for 6 months was well tolerated and blunted the postprandial increase in circulating lactate. However, it did not improve neurologic or other measures of clinical outcome.

Acidosis, Lactic↗

PubMed2006

Cystic fibrosis transmembrane conductance regulator deficiency exacerbates islet cell dysfunction after beta-cell injury.

The cause of cystic fibrosis-related diabetes (CFRD) remains unknown, but cystic fibrosis transmembrane conductance regulator (CFTR) mutations contribute directly to multiple aspects of the cystic fibrosis phenotype. We hypothesized that susceptibility to islet dysfunction in cystic fibrosis is determined by the lack of functional CFTR. To address this, glycemia was assessed in CFTR null (CFTR(-/-)), C57BL/6J, and FVB/NJ mice after streptozotocin (STZ)-induced beta-cell injury. Fasting blood glucose levels were similar among age-matched non-STZ-administered animals, but they were significantly higher in CFTR(-/-) mice 4 weeks after STZ administration (288.4 +/- 97.4, 168.4 +/- 35.9, and 188.0 +/- 42.3 mg/dl for CFTR(-/-), C57BL/6J, and FVB/NJ, respectively; P < 0.05). After intraperitoneal glucose administration, elevated blood glucose levels were also observed in STZ-administered CFTR(-/-) mice. STZ reduced islets among all strains; however, only CFTR(-/-) mice demonstrated a negative correlation between islet number and fasting blood glucose (P = 0.02). To determine whether a second alteration associated with cystic fibrosis (i.e., airway inflammation) could impact glucose control, animals were challenged with Aspergillus fumigatus. The A. fumigatus-sensitized CFTR(-/-) mice demonstrated similar fasting and stimulated glucose responses in comparison to nonsensitized animals. These studies suggest metabolic derangements in CFRD originate from an islet dysfunction inherent to the CFTR(-/-) state.

Animals↗

PubMed2005

Transcobalamin 776C->G polymorphism negatively affects vitamin B-12 metabolism.

BACKGROUND: A common genetic polymorphism [transcobalamin (TC) 776C-->G] may affect the function of transcobalamin, the protein required for vitamin B-12 cellular uptake and metabolism. Remethylation of homocysteine is dependent on the production of 5-methyltetrahydrofolate and adequate vitamin B-12 for the methionine synthase reaction. OBJECTIVES: The objectives were to assess the influence of the TC 776C--> G polymorphism on concentrations of the transcobalamin-vitamin B-12 complex (holo-TC) and to determine the combined effects of the TC 776C-->G and methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphisms and vitamin B-12 status on homocysteine concentrations. DESIGN: Healthy, nonpregnant women (n = 359; aged 20-30 y) were screened to determine plasma vitamin B-12, serum holo-TC, and plasma homocysteine concentrations and TC 776C-->G and MTHFR 677C-->T genotypes. RESULTS: The serum holo-TC concentration for women with the variant TC 776 GG genotype was significantly different (P = 0.0213) from that for subjects with the CC genotype (74 +/- 37 and 87 +/- 33 pmol/L, respectively). An inverse relation was observed between plasma homocysteine concentrations and both serum holo-TC (P </= 0.0001) and plasma vitamin B-12 (P </= 0.0001) concentrations, regardless of genotype. CONCLUSIONS: These data suggest that the TC 776C-->G polymorphism negatively affects the serum holo-TC concentration and provide additional evidence that vitamin B-12 status modulates the homocysteine concentration in this population.

Adult↗

PubMed2005

The effect of propofol on thermal pain perception.

We studied the effect of propofol, a widely used sedative-hypnotic drug, on pain perception. Eighteen subjects received propofol in two sedative concentrations that were balanced and randomized in order. Painful (45 degrees C, 47 degrees C, and 49 degrees C) stimulation temperatures were presented in random order, and nonpainful 31 degrees C stimuli were presented on alternate trials. We used a target-controlled infusion and chose effect site concentrations of 0.5 mug/mL for mild sedation and 1.0 mug/mL for moderate sedation. Using a visual analog scale, subjects rated both pain intensity and unpleasantness higher when sedated with propofol. The average pain intensity was 28/100 for placebo, 35/100 for mild, and 40/100 for moderate sedation. Pain unpleasantness was 23/100 for placebo, 29/100 for mild, and 33/100 for moderate sedation. This effect was unexpected and may be explained by a difference of subjective pain experience by a patient and the perceived level of analgesia by a health care provider in sedated patients. This finding calls further attention to the need for adequate analgesia in patients sedated with propofol.

Adult↗

PubMed2004

Methylenetetrahydrofolate reductase 677C-->T polymorphism affects DNA methylation in response to controlled folate intake in young women.

DNA methylation is critical for normal genomic structure and function and is dependent on adequate folate status. A polymorphism (677C-->T) in a key folate enzyme, methylenetetrahydrofolate reductase (MTHFR), may impair DNA methylation when folate intake is inadequate and may increase the risk of reproductive abnormalities. The present study was designed to evaluate the effect of the MTHFR 677C-->T polymorphism on changes in global DNA methylation in young women consuming a low folate diet followed by repletion with the current Recommended Dietary Allowance (RDA). Women (age 20-30 years) with the TT (variant; n = 19) or CC (n = 22) genotype for the MTHFR 677C-->T polymorphism participated in a folate depletion-repletion study (7 weeks, 115 microg DFE/day; 7 weeks, 400 microg DFE/day). DNA methylation was measured at baseline, week 7, and week 14 using a [3H]methyl acceptance assay and a novel liquid chromatography tandem mass spectrometry assay of the DNA bases methylcytosine and cytosine. [3H]Methyl group acceptance tended to increase (P = 0.08) during depletion in all subjects, indicative of a decrease in global DNA methylation. During repletion, the raw change and the percent change in the methylcytosine/total cytosine ratio increased (P = 0.03 and P = 0.04, respectively) only in the subjects with the TT genotype. Moderate folate depletion in young women may cause a decrease in overall DNA methylation. The response to folate repletion suggests that following folate depletion women with the MTHFR 677 TT genotype have a greater increase in DNA methylation with folate repletion than women with the CC genotype.

Adult↗

PubMed2004

Methionine synthase reductase 66A->G polymorphism is associated with increased plasma homocysteine concentration when combined with the homozygous methylenetetrahydrofolate reductase 677C->T variant.

Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) are important for homocysteine remethylation. This study was designed to determine the influence of genetic variants (MTHFR 677C-->T, MTHFR 1298A-->C, and MTRR 66A-->G), folate, and vitamin B-12 status on plasma homocysteine in women (20-30 y; n = 362). Plasma homocysteine was inversely (P < 0.0001) associated with serum folate and plasma vitamin B-12 regardless of genotype. Plasma homocysteine was higher (P < 0.05) for women with the MTHFR 677 TT/1298 AA genotype combination compared with the CC/AA, CC/AC, and CT/AA genotypes. Women with the MTHFR 677 TT/MTRR 66 AG genotype had higher (P < 0.05) plasma homocysteine than all other genotype combinations except the TT/AA and TT/GG genotypes. There were 5.4-, 4.3-, and 3.8-fold increases (P < 0.001) in risk for plasma homocysteine in the top 5, 10, and 20%, respectively, of the homocysteine distribution for subjects with the MTHFR 677 TT compared with the CC and CT genotypes. Predicted plasma homocysteine was inversely associated with serum folate (P = 0.003) and plasma vitamin B-12 (P = 0.002), with the degree of correlation dependent on MTHFR 677C-->T genotype. These data suggest that coexistence of the MTHFR 677 TT genotype with the MTRR 66A-->G polymorphism may exacerbate the effect of the MTHFR variant alone. The potential negative effect of combined polymorphisms of the MTHFR and MTRR genes on plasma homocysteine in at-risk population groups with low folate and/or vitamin B-12 status, such as women of reproductive potential, deserves further investigation.

Adult↗

PubMed2004

Methylphenidate does not improve cognitive function in healthy sleep-deprived young adults.

BACKGROUND: Abuse of methylphenidate, a treatment of attention-deficit/hyperactivity disorder, is reported to be increasing among students for the purpose of improving cognition. METHODS: A single capsule, containing methylphenidate (20 mg) or placebo, was administered to healthy young adults orally following 24 hours of sleep deprivation. Measurements included percent change in score from sleep-deprived baseline on four standardized tests of cognitive function: Hopkins Verbal Learning, Digit Span, Modified Stroop, and Trail Making tests. Measurements also included percent changes in blood pressure and heart rate from sleep-deprived baseline and plasma methylphenidate concentration. RESULTS: Differences in cognitive test performance were not observed between intervention groups. In subjects receiving methylphenidate, mean percent changes from baseline for systolic blood pressure and heart rate were increased relative to placebo between 90 and 210 minutes following capsule administration (maximum increases of 9.45% and 11.03%, respectively). The timing of peak differences in physiologic measures did not correlate with peak serum methylphenidate concentrations. Exit questionnaire ratings of "capsule effect" and perceived performance on the postcapsule administration of the most challenging cognitive test were both higher (p = .044 and p = .009, respectively) for the methylphenidate group than for the placebo group. CONCLUSIONS: Cognitive improvement among sleep-deprived young adults was not observed following methylphenidate administration. Benefits perceived by abusers may relate to increased confidence and sense of well-being, as well as to sympathetic nervous system stimulation. Moreover, methylphenidate administration results in physiologic effects that could be harmful to certain individuals.

Adult↗

PubMed2004

Differential metabolic effects of saturated versus polyunsaturated fats in ketogenic diets.

Ketogenic diets (KDs) are used for treatment of refractory epilepsy and metabolic disorders. The classic saturated fatty acid-enriched (SAT) KD has a fat:carbohydrate plus protein ratio of 4:1, in which the predominant fats are saturated. We hypothesized that a polyunsaturated fat-enriched (POLY) KD would induce a similar degree of ketosis with less detrimental effects on carbohydrate and lipid metabolism. Twenty healthy adults were randomized to two different weight-maintaining KDs for 5 d. Diets were 70% fat, 15% carbohydrate, and 15% protein. The fat contents were 60 or 15% saturated, 15 or 60% polyunsaturated, and 25% monounsaturated for SAT and POLY, respectively. Changes in serum beta-hydroxybutyrate, insulin sensitivity (S(I)), and lipid profiles were measured. Mean circulating beta-hydroxybutyrate levels increased 8.4 mg/dl in the POLY group (P = 0.0004), compared with 3.1 mg/dl in the SAT group (P = 0.07). S(I) increased significantly in the POLY group (P = 0.02), whereas total and low-density lipoprotein cholesterol increased significantly in the SAT group (both P = 0.002). These data demonstrate that a short-term POLY KD induces a greater level of ketosis and improves S(I), without adversely affecting total and low-density lipoprotein cholesterol, compared with a traditional SAT KD. Thus, a POLY KD may be superior to a classical SAT KD for chronic administration.

3-Hydroxybutyric Acid↗

PubMed2003

Folate catabolite excretion is responsive to changes in dietary folate intake in elderly women.

BACKGROUND: The major route of folate turnover is by catabolic cleavage of the C9-N10 bond producing p-aminobenzoylglutamate (pABG) and its primary excretory form, p-acetamidobenzoylglutamate (ApABG). We hypothesize that total pABG (ApABG + pABG) excretion parallels both the mass of body folate pools from which these catabolites originate and the folate-status indicators. OBJECTIVE: The objective was to determine whether urinary folate catabolite excretion reflects body pool size and parallels the static and functional measures of folate status. DESIGN: Urinary folate catabolite excretion was measured in women (aged 60-85 y) consuming controlled amounts of folate for 14 wk. A low-folate diet (120 microg/d) was consumed (n = 33) for 7 wk, and then subjects were randomly assigned to consume either 200 (n = 14) or 400 (n = 16) microg folate/d. Urinary pABG and ApABG concentrations were measured by HPLC at 0, 7, and 14 wk. RESULTS: Urinary excretion of total pABG was significantly lower (P = 0.001) after depletion (73.9 +/- 4.7 nmol/d) than at baseline (115 +/- 12.7 nmol/d). This rate of decline (approximately 0.7% per day) is consistent with the kinetically measured rate of turnover of total body folate at moderate folate intakes. The average percentage increase in total pABG in response to folate repletion with 400 microg/d (75%) was significant (P = 0.02). Folate catabolite excretion was significantly (P = 0.0001) associated with serum and red blood cell folate, plasma homocysteine, and DNA hypomethylation after depletion and with serum folate (P = 0.001) and plasma homocysteine (P = 0.0002) after repletion with 400 microg folate/d. CONCLUSIONS: Total urinary pABG excretion reflects total body folate pool size and is a long-term indicator that parallels functional measures of folate status.

4-Aminobenzoic Acid↗

PubMed2003

Folate status response to controlled folate intake is affected by the methylenetetrahydrofolate reductase 677C-->T polymorphism in young women.

This study was designed to evaluate the effect of the methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism on folate and homocysteine response in non-Hispanic women consuming a low folate diet followed by a diet providing the Recommended Dietary Allowance (RDA) for folate. Women (aged 20-30 y old) with either the TT (n = 19) or CC (n = 22) MTHFR 677C-->T genotype participated in a folate depletion-repletion study (7 wk, 115 microg dietary folate equivalents (DFE)/d; 7 wk, 400 microg DFE/d). Overall serum folate decreased (P < 0.0001) during depletion and increased (P < 0.0001) during repletion with lower (P = 0.03) postdepletion serum folate in women with the TT versus CC genotype. Folate status was low (serum folate < 13.6 nmol/L) in more women with the TT (59%) compared with the CC genotype (15%) postdepletion. Red blood cell folate for all subjects decreased during depletion (P < 0.0001) and repletion (P = 0.02) with lower (P = 0.04) red blood cell folate in women with the TT compared with the CC genotype postrepletion. Homocysteine increased (P < 0.0001) for both genotype groups postdepletion and decreased (P = 0.02) postrepletion for the CC genotype group only. Homocysteine concentrations tended to be higher (P = 0.09) in the TT versus CC genotype group postdepletion and postrepletion. These data suggest that the MTHFR 677C-->T polymorphism negatively affects the folate and homocysteine response in women consuming low folate diets followed by repletion with the RDA. These results may be important when evaluating the impact of the MTHFR 677C-->T polymorphism in countries in which low folate diets are chronically consumed.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗

PubMed2003

Exercise training, without weight loss, increases insulin sensitivity and postheparin plasma lipase activity in previously sedentary adults.

OBJECTIVE: To determine the effects of exercise, without weight loss, on insulin sensitivity (S(I)), postheparin plasma lipase activity (PHPL), intravenous fat clearance rate (K(2)), and fasting lipids in sedentary adults. RESEARCH DESIGN AND METHODS: At baseline and after 6 months of walk training (intensity 45-55 or 65-75% heart rate reserve, frequency 3-4 or 5-7 days/week, duration 30 min/session), anthropometric indexes, S(I), PHPL, K(2), and fasting lipids were measured in 18 sedentary adults (12 women, 6 men; 51.9 +/- 5.8 years of age, BMI 28.9 +/- 4.6 kg/m(2)). RESULTS: Exercise increased S(I) (2.54 +/- 2.74 vs. 4.41 +/- 3.30 microU ml(-1) x min(-1), P < 0.005) and both lipoprotein lipase (LPL) (1890 +/- 1380 vs. 4926 +/- 1858 nEq free fatty acid [FFA]. ml(-1). h(-1)) and hepatic lipase (HL) activities (3326 +/- 1605 vs. 4636 +/- 1636 nEq FFA. ml(-1) x h(-1)) (both P < 0.001), without altering BMI, waist circumference, K(2), or fasting lipids. Correlations between changes in LPL and the total:HDL cholesterol ratio (r = -0.54) and changes in the LPL:HL ratio and waist circumference (r = -0.50) were significant (P < 0.05). CONCLUSIONS: Exercise, without weight loss, increases S(I) and PHPL activity in previously sedentary adults, without changing K(2) or fasting lipid levels. Furthermore, increased LPL is associated with a decreased total:HDL ratio, and an increased LPL:HL ratio is associated with a decreased waist circumference. Therefore, even modest amounts of exercise in the absence of weight loss positively affect markers of glucose and fat metabolism in previously sedentary, middle-aged adults.

Biomarkers↗

PubMed2002

Renal manifestations of congenital lactic acidosis.

Congenital lactic acidoses (CLAs) constitute a group of rare inborn errors of mitochondrial metabolism in which cellular energy failure is the defining biochemical abnormality. We report the principal manifestations of renal dysfunction in 35 children with CLA caused by defects in either the pyruvate dehydrogenase multienzyme complex or one or more components of the respiratory chain. The most prominent renal abnormalities included bicarbonaturia, phosphaturia, hypercalciuria, complete Fanconi's syndrome, proteinuria, and decreased glomerular filtration rate. These data were compared with those from 79 previously published cases. Clinical manifestations of renal dysfunction in CLA are common and may be the first presenting sign of the disease. The glomerulus and proximal renal tubule appear to be the anatomic sites most vulnerable to abnormal mitochondrial energy transduction. We propose that the primary defect in mitochondrial energy metabolism, together with the consequent intracellular accumulation of lactate and hydrogen ions, precipitates a state of tissue injury that, unless interrupted, becomes self-perpetuating and ultimately leads to renal cell death.

Acidosis, Lactic↗