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Arthur J McCullough

Publications and source records attributed to Arthur J McCullough.

At least 19 recordsLinked to original sources
PubMed2006

Altered expression of genes regulating skeletal muscle mass in the portacaval anastomosis rat.

We examined the temporal relationship between portacaval anastomosis (PCA), weight gain, changes in skeletal muscle mass and molecular markers of protein synthesis, protein breakdown, and satellite cell proliferation and differentiation. Male Sprague-Dawley rats with end to side PCA (n=24) were compared with sham-operated pair-fed rats (n=24). Whole body weight, lean body mass, and forelimb grip strength were determined at weekly intervals. The skeletal muscle expression of the ubiquitin proteasome system, myostatin, its receptor (the activin 2B receptor) and its signal, cyclin-dependent kinase inhibitor (CDKI) p21, insulin-like growth factor (IGF)-I and its receptor (IGF-I receptor-alpha), and markers of satellite cell proliferation and differentiation were quantified. PCA rats did not gain body weight and had lower lean body mass, forelimb grip strength, and gastrocnemius muscle weight. The skeletal muscle expression of the mRNA of ubiquitin proteasome components was higher in PCA rats in the first 2 wk followed by a lower expression in the subsequent 2 wk (P<0.01). The mRNA and protein of myostatin, activin 2B receptor, and CDKI p21 were higher, whereas IGF-I and its receptor as well as markers of satellite cell function (proliferating nuclear cell antigen, myoD, myf5, and myogenin) were lower at weeks 3 and 4 following PCA (P < 0.05). We conclude that PCA resulted in uninhibited proteolysis in the initial 2 wk. This was followed by an adaptive response in the later 2 wk consisting of an increased expression of myostatin that may have contributed to reduced muscle protein synthesis, impaired satellite cell function, and lower skeletal muscle mass.

Activin Receptors, Type II↗
PubMed2006

Inhibition of aromatase improves nutritional status following portacaval anastomosis in male rats.

BACKGROUND/AIMS: The portacaval anastamosis (PCA) rat is a model of the nutritional and endocrine consequences of liver cirrhosis. We hypothesized that failure to gain body weight in the PCA rat was the consequence of low testosterone levels and will be reversed by 4-hydroxyandrostenedione, a specific aromatase inhibitor. METHODS: Male Sprague-Dawley rats subjected to an end-to-side PCA or sham surgery were administered either 4-hydroxyandrostenedione or vehicle. Food intake, food efficiency, and body weight were measured, animals sacrificed 3 weeks after surgery, visceral organs harvested and plasma sex steroids measured. Hepatic RNA was extracted and dot blots done to quantify the expression of sex hormone dependent enzymes 16alpha hydroxylase and 15beta hydroxylase. RESULTS: Growth, food intake, food efficiency and plasma testosterone were lower and plasma estradiol higher in PCA than sham rats. Hepatic expression of testosterone driven 16alpha hydroxylase was lower and estradiol driven 15beta hydroxylase higher in PCA rats. These alterations were reversed by 4-hydroxyandrostenedione. CONCLUSIONS: These observations demonstrate that use of aromatase inhibitor reverses the nutritional and endocrine abnormalities in the PCA rat and suggest that this approach may be useful in cirrhotic patients.

Animals↗
PubMed2006

In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease.

In patients with nonalcoholic fatty liver disease (NAFLD), a liver biopsy remains the only reliable way to differentiate simple steatosis from nonalcoholic steatohepatitis (NASH). Noninvasive methods are urgently needed. Increasing evidence suggests hepatocyte apoptosis is a key mediator of liver injury in NAFLD. The aim of this study was to quantify hepatocyte apoptosis in plasma from patients with NAFLD and correlate it with histological severity. Plasma was obtained from 44 consecutive patients with suspected NAFLD at the time of liver biopsy. Histology was assessed blindly. Caspase-3-generated cytokeratin-18 fragments were measured in situ via immunohistochemistry and in vivo using a novel enzyme-linked immunosorbent assay. Plasma cytokeratin-18 fragments were markedly increased in patients with NASH compared with patients with simple steatosis or normal biopsies (median [interquartile range]: 765.7 U/L [479.6-991.1], 202.4 U/L [160.4-258.2], 215.5 U/L [150.2-296.2], respectively; P < .001). Cytokeratin-18 fragment levels independently predicted NASH (OR 1.95; 95% CI 1.18-3.22; P = .009 for every 50 U/L increase). A cutoff value of 395 U/L calculated using the receiver operating characteristic curve approach showed a specificity of 99.9%, a sensitivity of 85.7%, and positive and negative predictive values of 99.9% and 85.7%, respectively, for the diagnosis of NASH. In conclusion, these findings strongly suggest that determination of hepatocyte caspase activation in the blood is a strong and independent predictor of NASH in human subjects. These data highlight the potential usefulness of this test as a noninvasive diagnostic means of determining histological disease severity in patients with NAFLD.

Apoptosis↗
PubMed2006

Smoking and increased severity of hepatic fibrosis in primary biliary cirrhosis: A cross validated retrospective assessment.

An epidemiological association between cigarette smoking and primary biliary cirrhosis (PBC) has been demonstrated. Our aim was to determine the relationship between smoking and severity of liver fibrosis at presentation in patients with PBC. All patients with PBC seen at the three major teaching hospitals of Case Western Reserve University between October 1998 and December 2005 were identified. Data obtained at the time of the first evaluation leading to the PBC diagnosis on 97 patients were collected. The cumulative number of cigarette packs smoked per year (pack-years) was calculated. Advanced histological disease was defined as Ludwig stages 3 or 4. Analyses were performed to determine associations between advanced histological disease, smoking and other variables related to liver fibrosis. Smoking history was more common (P = .0008) in patients with advanced histological disease at presentation compared to those with early disease. Among smokers, mean lifetime tobacco consumption was higher (P = .04) in cases with advanced histological disease at presentation (30 pack-years) compared to cases with early disease (17 pack-years). Logistic regression demonstrated a significant association between a lifetime tobacco consumption of > or =10 pack-years and advanced histological disease at presentation (OR = 13.3). The association remained significant after adjusting for age, gender, and alcohol intake. The validity of these results was corroborated by cross-validation in an independent confirmatory set of 172 patients with PBC. In conclusion, smoking may accelerate the progression of PBC. This could be induced by exposure to chemicals in cigarette smoke.

Alcohol Drinking↗
PubMed2006

Improving compliance with postpolypectomy surveillance guidelines: an interventional study using a continuous quality improvement initiative.

BACKGROUND: Despite guidelines, physicians tend to perform postpolypectomy surveillance colonoscopies too frequently. OBJECTIVE: The objective of the study was to determine the baseline compliance rate with postpolypectomy guidelines in our unit and to determine the influence of a continuous quality improvement (CQI) intervention on improving the compliance rate and on decreasing the potential additional costs because of the scheduling of postpolypectomy surveillance colonoscopies earlier than indicated. DESIGN: This was a single-arm, pretest-posttest design. SETTING: This study took place at a tertiary care, academic medical center. PATIENTS: The medical records of all patients who underwent colonoscopy with polypectomy in our unit retrospectively during 6 months preceding (baseline period) and prospectively for 6 months after an intervention (postintervention period) were reviewed for patient demographics, colonoscopy findings, and scheduling of repeat colonoscopies. INTERVENTION: We used 3 components: (1) distribution of a wallet-size card with a summary of postpolypectomy guidelines to all endoscopists, (2) placement of guideline charts near computers used for typing endoscopy reports, and (3) distribution and reinforcement of the guidelines in a monthly continuous quality improvement meeting. MAIN OUTCOME MEASURES: The main outcome measures were compliance rates, mean times to repeat colonoscopy, and additional costs from surveillance colonoscopies being scheduled earlier than indicated were compared between the two periods. RESULTS: There were 278 patients in the baseline period and 242 in the postintervention period, with similar patient and polyp characteristics. After the intervention, the compliance rate with guidelines improved from 57.2% to 81% (p < 0.001). The mean time to a repeat colonoscopy increased from 4.5 to 5.2 years (p = 0.003) (i.e., a 14% reduction in the number of postpolypectomy surveillance colonoscopies performed per year). This would result in a reduction of a total of 73 surveillance colonoscopies per year in our unit, with a projected cost savings of 171,331 dollars per year (cost of a colonoscopy assumed at 2347 dollars). LIMITATIONS: The limitation of the study was possible enhanced performance secondary to being observed (Hawthorne effect). Because more than 1 intervention was used, we do not know which one is more effective. CONCLUSIONS: Relatively simple and easy-to-implement quality improvement initiatives can significantly enhance compliance with postpolypectomy guidelines and result in cost savings because of a reduction in the number of postpolypectomy surveillance colonoscopies being scheduled earlier than recommended guidelines.

Colonoscopy↗
PubMed2006

Pathophysiology of nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) affects approximately 30% of adults and 20% of children in the United States. Nonalcoholic steatohepatitis (NASH) is its most severe histologic form and progresses to cirrhosis in 20% of these patients. Once developed, 30% to 40% of patients with NASH cirrhosis will experience a liver-related death. Consequently, it has become extremely important to understand the pathophysiology of NASH to develop sound therapeutic interventions. It is now recognized that nonhepatic mechanisms are largely responsible for the development of insulin resistance, which causes hepatic steatosis. Once developed, oxidative stress and diminished antioxidants within the liver initiate the progression from steatosis alone to NASH and ultimately to cirrhosis. However, not all patients progress to cirrhosis. As is the case for other common complex metabolic diseases, it is the interaction between the environment and genetics that will determine the phenotypic expression of NAFLD and NASH in each individual patient. Which of the pathophysiologic factors (which are discussed in this review), either alone or in combination, will eventually provide the basis for the most effective therapy has yet to be determined.

Animals↗
PubMed2006

Afternoon colonoscopies have higher failure rates than morning colonoscopies.

BACKGROUND: There are several known predictors of an incomplete colonoscopy or difficult colonoscopy. In addition, inadequate bowel preparation has been reported in procedures scheduled later in the day. Operator fatigue, which tends to be higher as the day passes on, may also impact colonoscopy completion rate. AIMS: To determine the influence of performing outpatient colonoscopies in the afternoon versus morning on the completion rates of colonoscopy and adequacy of bowel preparation. METHODS: Retrospective chart review of all outpatient colonoscopies performed between November 2003 and October 2004 in the Division of Gastroenterology at MetroHealth Medical Center in Cleveland, Ohio. Patient demographics, indications for procedure, and colonoscopic findings were reviewed. Patients received polyethylene glycol electrolyte-based bowel preparation in the evening prior to the day of the scheduled colonoscopy. RESULTS: A total of 2,087 colonoscopies was performed, of which 1,084 were in the morning and 999 were in the afternoon. Patients in the morning and afternoon were similar in regards to the known risk factors predictive of an incomplete colonoscopy. The incompletion rate was significantly higher in the afternoon compared to the morning (6.5% vs 4.1%, P= 0.013, OR for incompletion was 1.64, CI 1.11-2.44). Inadequate bowel preparation was found in 167 out of 1,084 (15.4%) colonoscopies in the morning and 197 out of 999 (19.7%) colonoscopies in the afternoon (P= 0.011). Even after excluding incomplete colonoscopies due to poor bowel preparation precluding examination, the incompletion rate was still higher in the afternoon (5% vs 3.2%, P= 0.043, OR 1.60, CI 1.03-2.51). CONCLUSIONS: Scheduling of colonoscopies in the afternoon compared to the morning may be an independent predictor of an incomplete colonoscopy and inadequate bowel preparation. According to our study findings, scheduling of all outpatient colonoscopies preferentially in the morning would avoid suboptimal procedures in 5% of patients and the need for unnecessary repeat colonoscopy or an alternative imaging study in 2.4% of patients.

Aged↗
PubMed2005

Design and validation of a histological scoring system for nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of a history of significant alcohol use or other known liver disease. Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD. The Pathology Committee of the NASH Clinical Research Network designed and validated a histological feature scoring system that addresses the full spectrum of lesions of NAFLD and proposed a NAFLD activity score (NAS) for use in clinical trials. The scoring system comprised 14 histological features, 4 of which were evaluated semi-quantitatively: steatosis (0-3), lobular inflammation (0-2), hepatocellular ballooning (0-2), and fibrosis (0-4). Another nine features were recorded as present or absent. An anonymized study set of 50 cases (32 from adult hepatology services, 18 from pediatric hepatology services) was assembled, coded, and circulated. For the validation study, agreement on scoring and a diagnostic categorization ("NASH," "borderline," or "not NASH") were evaluated by using weighted kappa statistics. Inter-rater agreement on adult cases was: 0.84 for fibrosis, 0.79 for steatosis, 0.56 for injury, and 0.45 for lobular inflammation. Agreement on diagnostic category was 0.61. Using multiple logistic regression, five features were independently associated with the diagnosis of NASH in adult biopsies: steatosis (P = .009), hepatocellular ballooning (P = .0001), lobular inflammation (P = .0001), fibrosis (P = .0001), and the absence of lipogranulomas (P = .001). The proposed NAS is the unweighted sum of steatosis, lobular inflammation, and hepatocellular ballooning scores. In conclusion, we present a strong scoring system and NAS for NAFLD and NASH with reasonable inter-rater reproducibility that should be useful for studies of both adults and children with any degree of NAFLD. NAS of > or =5 correlated with a diagnosis of NASH, and biopsies with scores of less than 3 were diagnosed as "not NASH."

Adult↗
PubMed2005

Insulin resistance: a metabolic pathway to chronic liver disease.

Insulin resistance (IR) is the pathophysiological hallmark of nonalcoholic fatty liver disease (NAFLD), one of the most common causes of chronic liver disease in Western countries. We review the definition of IR, the methods for the quantitative assessment of insulin action, the pathophysiology of IR, and the role of IR in the pathogenesis of chronic liver disease. Increased free fatty acid flux from adipose tissue to nonadipose organs, a result of abnormal fat metabolism, leads to hepatic triglyceride accumulation and contributes to impaired glucose metabolism and insulin sensitivity in muscle and in the liver. Several factors secreted or expressed in the adipocyte contribute to the onset of a proinflammatory state, which may be limited to the liver or more extensively expressed throughout the body. IR is the common characteristic of the metabolic syndrome and its related features. It is a systemic disease affecting the nervous system, muscles, pancreas, kidney, heart, and immune system, in addition to the liver. A complex interaction between genes and the environment favors or enhances IR and the phenotypic expression of NAFLD in individual patients. Advanced fibrotic liver disease is associated with multiple features of the metabolic syndrome, and the risk of progressive liver disease should not be underestimated in individuals with metabolic disorders. Finally, the ability of insulin-sensitizing, pharmacological agents to treat NAFLD by reducing IR in the liver (metformin) and in the periphery (thiazolidinediones) are discussed.

Chronic Disease↗
PubMed2005

Treatment of alcoholic hepatitis.

Cirrhosis and its sequelae are responsible for close to 2% of all causes of death in the United States. Some studies have suggested that the costs of liver disease may account for as much as 1% of all health care spending, with alcohol-related liver disease (ALD) representing a major portion. It accounts for between 40% to 50% of all deaths due to cirrhosis, with an accompanying rate of progression of up to 60% in patients with pure alcoholic fatty liver over 10 years, and a 5-year survival rate as low as 35% if patients continue to drink. A subset of patients with ALD will develop an acute, virulent form of injury, acute alcoholic hepatitis, which has a substantially worse prognosis. Despite enormous progress in understanding the physiology of this disease, much remains unknown, and therefore, a consensus regarding effective therapy for ALD is lacking. Conventional therapy is still based largely on abstinence from alcohol, as well as general supportive and symptomatic care. Unfortunately, hepatocellular damage may progress despite these measures. Multiple treatment interventions for both the short- and long-term morbidity and mortality of this disease have been proposed, but strong disagreement exists among experts regarding the value of any of the proposed specific therapeutic interventions.

Adrenal Cortex Hormones↗
PubMed2004

Skeletal muscle atrophy is associated with an increased expression of myostatin and impaired satellite cell function in the portacaval anastamosis rat.

Proliferation and differentiation of satellite cells are critical in the regeneration of atrophied muscle following immobilization and aging. We hypothesized that impaired satellite cell function is responsible for the atrophy of skeletal muscle also seen in cirrhosis. Myostatin and insulin-like growth factor 1 (IGF1) have been identified to be positive and negative regulators, respectively, of satellite cell function. Using a rat model of cirrhosis [portacaval anastamosis (PCA)] and sham-operated controls, we examined the expression of myostatin, its receptor activinR2b, and its downstream messenger cyclin-dependent kinase inhibitor p21 (CDKI p21) as well as IGF1 and its receptor in the gastrocnemius muscle. Expression of PCNA, a marker of proliferation, and myogenic regulatory factors (myoD, myf5, and myogenin), markers of differentiation of satellite cells, were also measured. Real- time PCR for mRNA and Western blot assay for protein quantification were performed. PCA rats had lower body weight and gastrocnemius weight compared with sham animals (P < 0.05). PCNA and myogenic regulatory factors were lower in PCA rats (P < 0.05). Myostatin, activinR2b, and CDKI p21 were higher in the PCA animals (P < 0.05). The expression of IGF1 and its receptor was lower in liver and skeletal muscle of PCA animals (P < 0.05). These data suggest that skeletal muscle atrophy seen in the portacaval shunted rats is a consequence of impaired satellite cell proliferation and differentiation mediated, in part, by higher myostatin and lower IGF1 expression.

Animals↗
PubMed2004

The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease in the United States. The histologic spectrum of NAFLD ranges from steatosis liver alone to nonalcoholic steatohepatitis (NASH), which is the most serious form of NAFLD. NASH is a progressive fibrotic disease, in which cirrhosis and liver-related death occur in up to 20% and 12%, respectively, over a 10-year period. NASH-associated cirrhosis also can develop into subacute liver failure, progress to hepatocellular carcinoma, and reoccur post-transplantation. In contrast, steatosis alone has a more benign clinical course, although progression to cirrhosis has occurred in 3% of these patients. The major risk factors for fibrosis include diabetes or obesity, an aspartate aminotransferase/alanine aminotransferase ratio of greater than 1, age older than 50, and hepatic histology.

Adult↗
PubMed2004

Pathologic features associated with fibrosis in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of clinicopatholologic conditions ranging from steatosis alone to nonalcoholic steatohepatitis (NASH), with varying risks for progression to cirrhosis. Although steatosis alone seems to be nonprogressive, some patients with NASH can progress. This study focuses on the clinical and pathological characteristics of patients with NAFLD associated with the development of histological fibrosis. Patients with an established diagnosis of nonalcoholic fatty liver were identified through our NAFLD database containing extensive clinical, demographic, and laboratory data. Liver biopsy specimens were read blindly by one hepatopathologist using a 19-item pathological protocol and by another hepatopathologist using a second pathological protocol. Clinical and pathological data were matched to the presence of different types of histological fibrosis. Univariate and multivariate analyses helped determine all of the variables independently associated with histological fibrosis. Of 132 NAFLD patients, 21.2% had advanced fibrosis (septal/bridging fibrosis or well-established cirrhosis). Sinusoidal fibrosis was present in 20.3% of patients, whereas perivenular fibrosis was seen in 17.2%. Ballooning degeneration and Mallory bodies were independently associated with both sinusoidal fibrosis and perivenular fibrosis. Aspartate aminotransferase/alanine aminotransferase ratio and ballooning degeneration were also independently associated with periportal-portal fibrosis. We conclude that the presence of hepatocyte injury in NAFLD is associated with fibrosis. These pathological features can be used to establish the pathological criteria for diagnosis of the progressive form of NAFLD or NASH.

Adult↗
PubMed2004

Nonalcoholic fatty liver disease in patients with type 2 diabetes.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is reported commonly in patients with type 2 diabetes mellitus (DM), which has been suggested as a risk factor for the progressive form of NAFLD, or nonalcoholic steatohepatitis. The aim of this study was to assess the outcome of patients with NAFLD and DM. METHODS: A cohort of patients with NAFLD was identified, and patients with other causes of liver disease (alcohol, medication, etc.) were excluded. Clinical, pathological, and mortality data were available for this cohort. Patients were categorized and compared according to the presence or absence of DM. RESULTS: Of 132 patients with NAFLD, 44 patients (33%) had an established diagnosis of DM. Patients with DM were older and had greater serum glucose and triglyceride levels and a greater aspartate aminotransferase-alanine aminotransferase ratio. Liver biopsy specimens from patients with DM showed more vacuolated nuclei and acidophilic bodies. Cirrhosis (histological or clinical) occurred in 25% of patients with DM (11 of 44 patients) and NAFLD compared with only 10.2% (9 of 88 patients) of patients without DM with NAFLD (P = 0.04). After adjusting for potential confounders (age, body mass index, and the presence of cirrhosis), both overall mortality (risk ratio [RR], 3.30; 95% confidence interval [CI], 1.76-6.18; P = 0.002) and mortality related to liver disease (RR, 22.83; 95% CI, 2.97-175.03; P = 0.003) were greater in diabetic patients with NAFLD. Markers of hepatic dysfunction (low albumin level, high total bilirubin level, and prolonged prothrombin time) were the only independent predictors of increased mortality. CONCLUSIONS: Patients with NAFLD and DM are at risk for the development of an aggressive outcome, such as cirrhosis and mortality. This study supports the potential role of insulin resistance in the development of poor clinical outcomes in patients with NAFLD.

Age Distribution↗
PubMed2004

Obesity and non-alcoholic fatty liver disease in chronic hepatitis C.

BACKGROUND: Superimposed non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) may affect HCV-related fibrosis. We performed a study to determine the relationship between NAFLD and chronic hepatitis C. METHODS: One hundred and twenty patients with chronic hepatitis C and available liver biopsies were included. Baseline liver biopsies were read by 1 hepatopathologist using Metavir, as well as a fatty liver pathology protocol. Patients' baseline clinical, demographic, and virologic data were associated with the extent of steatosis (>33% vs. < or =33%), the type of fatty liver (no steatosis vs. steatosis only vs. NASH), and the stage of fibrosis seen on the liver biopsy. RESULTS: Seventy percent of patients were men and 80% were white. The mean age was 47.48+/-5.70 years, mean BMI was 29.01 +/-5.01 kg/m, and mean waist to hip ratio (W/H) was 0.90+/-0.08. Patients with higher grade of steatosis had higher BMI (32.83+/-6.26 vs. 28.49+/-4.62, P = 0.034), more likely to have genotype 3 (21.4% vs. 5.7%, P = 0.037) and advanced fibrosis (92.9% vs. 62.3%, P = 0.033) than those with lower grade of steatosis. Of these, only HCV-genotype 3 remained independently associated with higher grade of steatosis. When patients with superimposed NASH (n = 22) were compared with those with only steatosis (n = 49) and those without steatosis (n = 49), patients with superimposed NASH had more evidence of obesity (BMI: 30.64+/-5.23 vs. 29.90+/-5.35 vs. 27.33+/-4.07, P = 0.008; W/H: 0.97+/-0.06 vs. 0.91+/-0.08 vs. 0.87+/-0.07, P < 0.001), more commonly infected with HCV genotype 3 (14% vs. 12% vs. 0%, P = 0.036) and had more advanced fibrosis (95.5% vs. 75.5% vs. 42.9%, P < 0.001). Race, gender, and age did not affect extent of steatosis or presence of superimposed NASH. CONCLUSION: In conclusion, markers of obesity (BMI and W/H) and HCV genotype 3 are associated with the extent of steatosis and type of fatty liver. Higher grade of steatosis and presence of superimposed NASH are both associated with advanced hepatic fibrosis.

Fatty Liver↗
PubMed2003

Gender differences in the regulation of amino acid metabolism.

Exercising men, compared with women, have a greater increase in leucine oxidation but not lysine rate of appearance. The cause for this sexual dimorphism is unknown; however, an inhibition of beta-adrenoreceptor activity has previously been shown to mediate amino acid metabolism (Lamont LS, McCullough AJ, and Kalhan SC. Am J Physiol Endocrinol Metab 268: E910-E916, 1995; Lamont LS, Patel DG, and Kalhan SC. J Appl Physiol 67: 221-225, 1989). This study was a gender comparison of leucine and lysine kinetics during a beta-adrenoreceptor blockade (beta1,beta2-blockade) and a placebo control by using a double-blind crossover protocol. Subjects exercised at 50% of their trial-specific maximal O2 consumption (1 h) after 7 days of dietary control. During exercise with beta-blockade, men had an increased nonprotein respiratory exchange ratio (P < 0.001), whereas women had an increased circulation of free fatty acids (P < 0.001). The genders also displayed distinct differences in exercise amino acid kinetics. The men, but not the women, increased leucine oxidation (P < 0.005) and lysine rate of appearance (P < 0.009) when exercising during beta-adrenergic blockade. This study indicates that during beta-blockade, exercising men increase their need for amino acids (and carbohydrate) to fuel energy needs, whereas women increase their mobilization of fat, thereby requiring less alternative fuels such as carbohydrate and amino acids. Gender-specific fuel preferences during exercise are regulated by beta-adrenergic-receptor activity. Substrate availability during exercise appears to modulate the amino acid oxidation differences between genders.

Adrenergic beta-Antagonists↗