A blinded randomized controlled trial of motivational interviewing to improve adherence with osteoporosis medications: design of the OPTIMA trial.

UNLABELLED: We have designed an innovative randomized controlled trial for improving adherence with osteoporosis medications. Recruitment and randomization have been successful. Also, the counseling intervention has been well accepted by subjects randomized to this treatment arm. INTRODUCTION: While many effective treatments exist for osteoporosis, most people do not adhere to such treatments long term. No proven interventions exist to improve osteoporosis medication adherence. We report here on the design and initial enrollment in an innovative randomized controlled trial aimed at improving adherence to osteoporosis treatments. METHODS: The trial represents a collaboration between academic researchers and a state-run pharmacy benefits program for low-income older adults. Beneficiaries beginning treatment with a medication for osteoporosis are targeted for recruitment. We randomize consenting individuals to receive 12 months of mailed education (control arm) or an intervention consisting of one-on-one telephone-based counseling and the mailed education. Motivational interviewing forms the basis for the counseling program which is delivered by seven trained and supervised health counselors over ten telephone calls. The counseling sessions include scripted dialog and open-ended questions about medication adherence and its barriers, as well as structured questions. The primary end point of the trial is medication adherence measured over the 12-month intervention period. Secondary end points include fractures, nursing home admissions, health care resource utilization, and mortality. RESULTS: During the first 7 months of recruitment, we have screened 3,638 potentially eligible subjects. After an initial mailing, 1,115 (30.6%) opted out of telephone recruitment and 1,019 (28.0%) could not be successfully contacted. Of the remaining, 879 (24.2%) consented to participate and were randomized. Women comprise over 90% of all groups; mean ages range from 77 to 80 years old, and the majority in all groups was white. The distribution of osteoporosis medications was comparable across groups and the median number of different prescription drugs used in the prior year was eight to ten. CONCLUSIONS: We have developed a novel intervention for improving osteoporosis medication adherence. The intervention is currently being tested in a large-scale randomized controlled trial. If successful, the intervention may represent a useful model for improving adherence to other chronic treatments.

Interventions to improve adherence and persistence with osteoporosis medications: a systematic literature review.

SUMMARY: Adherence and persistence with osteoporosis medications are poor. We conducted a systematic literature review of interventions to improve adherence and persistence with osteoporosis medications. Seven studies met eligibility requirements and were included in the review. Few interventions were efficacious, and no clear trends regarding successful intervention techniques were identified. However, periodic follow-up interaction between patients and health professionals appeared to be beneficial. INTRODUCTION: Adherence and persistence with pharmacologic therapy for osteoporosis are suboptimal. Our goal was to examine the design and efficacy of published interventions to improve adherence and persistence. METHODS: We searched medical literature databases for English-language papers published between January 1990 and July 2008. We selected papers that described interventions and provided results for control and intervention subjects. We assessed the design and methods of each study, including randomization, blinding, and reporting of drop-outs. We summarized the results and calculated effect sizes for each trial. RESULTS: Seven studies met eligibility requirements and were included in the review. Five of the seven studies provided adherence data. Of those five studies, three showed a statistically significant (p < or = 0.05) improvement in adherence by the intervention group, with effect sizes from 0.17 to 0.58. Five of the seven studies provided persistence data. Of those five, one reported statistically significant improvement in persistence by the intervention group, with an effect size of 0.36. CONCLUSIONS: Few interventions were efficacious, and no clear trends regarding successful intervention techniques were identified in this small sample of studies. However, periodic follow-up interaction between patients and health professionals appeared to be beneficial.

Modelling the role of groundwater hydro-refugia in East African hominin evolution and dispersal.

Water is a fundamental resource, yet its spatiotemporal availability in East Africa is poorly understood. This is the area where most hominin first occurrences are located, and consequently the potential role of water in hominin evolution and dispersal remains unresolved. Here, we show that hundreds of springs currently distributed across East Africa could function as persistent groundwater hydro-refugia through orbital-scale climate cycles. Groundwater buffers climate variability according to spatially variable groundwater response times determined by geology and topography. Using an agent-based model, grounded on the present day landscape, we show that groundwater availability would have been critical to supporting isolated networks of hydro-refugia during dry periods when potable surface water was scarce. This may have facilitated unexpected variations in isolation and dispersal of hominin populations in the past. Our results therefore provide a new environmental framework in which to understand how patterns of taxonomic diversity in hominins may have developed.

Comparative performance evaluation of the HIV-1 LiPA protease and reverse transcriptase resistance assay on clinical isolates.

BACKGROUND: Assays that provide information regarding HIV-1 resistance to antiretroviral drugs are widely used to help manage antiretroviral treatment. The most commonly used HIV genotypic resistance assays are based on DNA sequencing (TRUGENE, ViroSeq, and home-brew) or reverse hybridization (LiPA). OBJECTIVES: This study compares the results from clinical specimens using two assay methods: the LiPA HIV-1 protease (PR) and reverse transcriptase (RT) resistance assay and DNA sequencing. STUDY DESIGN: Operators at each of three sites tested 10-20 randomly selected clinical specimens using LiPA (three strips total with probes for PR codons 30, 46, 48, 50, 54, 82, 84, and 90, and RT codons 41, 69, 70, 74, 75, 103, 106, 151, 181, 184, and 215) and DNA sequencing (TRUGENE) HIV-1 Genotyping Assay or home-brew methodology). Results from the two methods were categorized for each codon as follows: (i) concordant (LiPA and sequencing having the same result for wild-type (WT), mutant, and mixture); (ii) partially concordant (mixture by one method and not by the other); (iii) indeterminate (no result by LiPA); and (iv) discordant (LiPA and sequencing detecting different amino acids). RESULTS: A total of 50 clinical specimens were tested using the LiPA PR strip; 40 of these were also tested using the LiPA RT strip. For PR, 91.3% of the codon results were concordant, 3.0% were partially concordant, 4.5% were indeterminate by LiPA, and 1.3% were discordant. For RT, 88.0% of the codon results were concordant, 5.9% were partially concordant, 5.2% were indeterminate, and 0.9% were discordant. LiPA detected 3.0% (PR) and 6.4% (RT) WT/mutant mixtures, compared to 0.5% (PR) and 3.2% (RT) mixtures by sequencing. CONCLUSIONS: More WT/mutant mixtures were detected using LiPA, possibly indicating increased sensitivity. Relatively high concordance and low discordance rates were observed between LiPA and DNA sequencing. The indeterminate rate for LiPA was moderately high and may limit the clinical utility of this assay.

Influence of endurance training on the age-related decline in hepatic glyconeogenesis.

Hepatic gluconeogenic and glyconeogenic capabilities were investigated in Fischer 344 rat livers (ages 7, 15 and 25 months; n = 66) to determine if endurance training affected age related decrements in these hepatic functions. Animals were trained 1 h/day, 5 days/week for 10 weeks at treadmill speeds of 75% of age-specific maximal capacity. After training, rats were injected (300 mg/kg) with a known gluconeogenic inhibitor, 3-mercaptopicolinic acid (MPA). Two endurance tests were performed to help assess the contribution of gluconeogenesis to exercise performance, an initial test 4 days prior to injection and a final test immediately post-injection. MPA significantly (P < 0.05) reduced running times in all trained groups compared to their control test: 89%, 81%, and 51% in the young, middle-aged, and old, respectively. MPA reduced running times in the untrained animals 19%, 11%, and 8%, respectively. Three days after the last exercise bout, the animals were anesthetized and liver sections were sliced and incubated in [14C]lactic acid or [14C]fructose. An age-related decline was found in [14C]lactate incorporation (middle-aged decreases 66%, old decreases 54%) and in [14C]fructose incorporation (middle-aged decreases 51%, old decreases 48%) into glycogen. Differences existed in lactate incorporation in trained compared to untrained animals for the young, middle-aged, and old groups: 150.1 +/- 11.3 vs. 102.1 +/- 10.0; 75.3 +/- 6.2 vs. 34.9 +/- 6.4; and 69.3 +/- 14.9 vs. 47.0 +/- 4.7 nmol/g/h, respectively. No differences were found with training in any of the age groups for fructose. Phosphoenolpyruvate carboxykinase (PEPCK) activity and messenger RNA (mRNA) were significantly reduced in the old compared to the young rats (decreases 64% and decreases 58%, respectively). No training effects were found for either PEPCK activity or mRNA for any age group. These results suggest that hepatic gluconeogenic and glyconeogenic capabilities declined with age. Training had an effect in attenuating the glyconeogenic decline but had a minimal effect in offsetting the age-related decline in PEPCK.

Postexercise thermoregulatory behavior and recovery from exercise in desert iguanas.

Desert iguanas (Dipsosaurus dorsalis) undergo respiratory recovery more rapidly and incur lower energetic costs when they recover from 40 degrees C burst activity at 20 degrees C than when they recover at 40 degrees C. However, a body temperature of 20 degrees C falls well outside the preferred activity temperature range of this species, and imposes several physiological and behavioral liabilities. To determine if exhausted animals would favor a thermal regimen that allows for rapid and inexpensive respiratory recovery, we exercised lizards to exhaustion and allowed them to recover in a laboratory thermal gradient for 180 min. Recovering animals allowed their body temperatures to cool significantly to a mean temperature of 33.5 degrees C during the first 60 min of recovery, and subsequently rewarmed themselves to an average temperature of 38 degrees C for the remainder of their recovery period. Control animals maintained a constant body temperature of 37.7 degrees C throughout the 180-min recovery period. We then exercised animals to exhaustion at 40 degrees C and allowed them to recover for 180 min under a thermal regimen that mimicked that selected by exhausted animals in the previous experiment. Animals recovering under this thermal regimen returned to rates of O2 consumption, removed exercise-generated blood lactate, and incurred energetic costs that were more similar to data previously collected for animals recovering from exercise at a constant 40 degrees C than to data from animals recovering at 20 degrees C. These results suggested that the energetic benefits associated with recovery at 20 degrees C are not of sufficient biological importance to cause a major shift in thermoregulatory behavior.

Maximal sprint speeds and muscle fiber composition of wild and laboratory house mice.

We compared males from four groups of house mice (Mus domesticus), all bred and raised under common conditions in the laboratory: randombred Hsd:ICR; a wild population from Wisconsin; hybrids from lab dams; hybrids from wild dams. Wild mice were much faster sprinters (maximal forced sprint speeds over 1.0 m ranged from 2.38 to 3.34 m/s) than were lab mice (range = 0.89-1.68 m/s). Hybrids exhibited intermediate speeds (range = 1.54-2.70 m/s) and body masses, indicating largely additive inheritance. Type-specific mean muscle fiber cross-sectional areas of the gastrocnemius muscle did not differ significantly among groups. Percentage cross-sectional areas occupied by each of the three identified fiber types also did not differ significantly among groups, nor did they covary with body mass. For their body mass, however, lab mice had smaller gastrocnemius muscles than did wild and hybrid mice, which had muscles of similar size. Although we cannot rule out the possibility that smaller gastrocnemius muscles or slight differences in fiber composition account for the lower sprint speeds of the lab mice, we suggest that differences in unmeasured physiological, behavioral or motivational factors are probably the primary cause. This interpretation is supported by a lack of correlation between individual differences in sprint speed and either relative gastrocnemius muscle mass or muscle fiber type composition.

Comparative analysis of fiber-type composition in the iliofibularis muscle of phrynosomatid lizards (Squamata).

The lizard family Phrynosomatidae comprises three subclades: the closely related sand and horned lizards, and their relatives the Sceloporus group. This family exhibits great variation in ecology, behavior, and general body plan. Previous studies also show that this family exhibits great diversity in locomotor performance abilities; as measured on a high-speed treadmill, sand lizards are exceptionally fast sprinters, members of the Sceloporus group are intermediate, and horned lizards are slowest. These differences are paralleled by differences in relative hindlimb span. To determine if muscle fiber-type composition also varies among the three subclades, we examined the iliofibularis (IF), a hindlimb muscle used in lizard locomotion, in 11 species of phrynosomatid lizards. Using histochemical assays for myosin ATPase, an indicator of fast-twitch capacity, and succinic dehydrogenase, denoting oxidative capacity, we classified fiber types into three categories based on existing nomenclature: fast-twitch glycolytic (FG), fast-twitch oxidative-glycolytic (FOG), and slow-twitch oxidative (SO). Sand lizards have a high proportion of FG fibers (64-70%) and a low proportion of FOG fibers (25-33%), horned lizards are the converse (FG fibers 25-31%, FOG fibers 56-66%), and members of the Sceloporus group are intermediate for both FG (41-48%) and FOG (42-45%) content. Hence, across all 11 species %FOG and %FG are strongly negatively correlated. Analysis with phylogenetically independent contrasts indicate that this negative relationship is entirely attributable to the divergence between sand and horned lizards. The %SO also varies among the three subclades. Results from conventional nested ANCOVA (with log body mass as a covariate) indicate that the log mean cross-sectional area of individual muscle fibers differs among species and is positively correlated with body mass across species, but does not differ significantly among subclades. The log cross-sectional area of the IF varies among species, but does not vary among subclades. Conversely, the total thigh muscle cross-sectional area does not vary among species, but does vary among subclades; horned lizards have slimmer thighs. Muscle fiber-type composition appears to form part of a coadapted suite of traits, along with relative limb and muscle sizes, that affect the locomotor abilities of phrynosomatid lizards.

Protection of chicks against Salmonella infection with a mixture of pure cultures of intestinal bacteria.

A mixture of 28 pure cultures was prepared from the organisms isolated from native gut microflora (fecal and cecal contents) of adult Salmonella-free birds. This mixture was orally administered to 1-day-old chicks and examined for its efficacy against challenge with 10(5) colony-forming units of nalidixic-acid-resistant Salmonella typhimurium in six consecutive trials during a 20-month period. The efficacy of the mixture, which was prepared for each trial from stored isolates, progressively decreased, while that from stored fecal content remained unimpaired. Twenty-three cultures in the mixture were tentatively identified as belonging to seven different genera; the genus of the five other cultures remained unknown.

High resolution computed tomography and magnetic resonance imaging in the pre-operative assessment of cochlear implant patients.

Optimal imaging protocols for cochlear implantation have yet to be determined. Pre-operative computed tomography (CT) and magnetic resonance image (MRI) scans are used to assess cochlear anatomy and patency, to delineate surgical access, and to aid in choice of side for implantation. However, opinion still differs as to which modality provides more information in pre-operative assessment, or if, indeed, a combination of the two is superior. The first 88 patients on the Irish National Cochlear Implant Programme (NCIP) were retrospectively studied to determine the accuracy of pre-operative CT and MRI in predicting abnormalities at the time of surgery. Correlation with surgical findings was determined in three separate groups of patients (those who had CT only, those who had MRI only, and those who had both CT and MRI performed). Of the 24 patients that had both CT and MRI performed, both modalities had a 79 per cent correlation with surgical findings. CT and MRI reports concurred in 75 per cent of cases. Specificity and negative predictive value were high (86 per cent and 90 per cent, respectively). CT alone (47 cases) correlated with surgery in 39 cases (83 per cent); MRI alone (17 cases) correlated in 15 cases (88 per cent). The findings of this study suggest that CT and MRI are effective at predicting normal inner ear anatomy, and thus at predicting the patient and the cochlea most suitable for implantation. Both modalities are useful in determining the side of implantation, thus avoiding potential surgical difficulties in cases of unilateral abnormalities. There was no significant difference between the ability of MRI and CT to detect abnormalities at the time of surgery. In this series the combination of CT and MRI has not been shown to be superior to either modality used alone, although anecdotal evidence to the contrary was noted.

Skeletal muscle substrate utilization is altered by acute and acclimatory temperature in the American bullfrog (Lithobates catesbeiana).

We investigated the effect of acute and acclimatory temperature on the relative contribution of g9lucose and lactate to metabolism in resting sartorius muscle of the American bullfrog (Lithobates catesbeiana). We examined the fate of these metabolites in vitro by supplying radiolabeled [(14)C]glucose, [(14)C]lactate and [(14)C]palmitate to isolated muscle bundles from frogs (1) acutely exposed to incubation conditions of 5, 15 or 25 degrees C, (2) acclimated for 2-6 weeks to 5 or 25 degrees C or (3) acclimated for 2-6 weeks to 5 or 25 degrees C and the muscles incubated at 15 degrees C. Under all three temperature conditions tested, net rate of lactate metabolism exceeded that of glucose. Acute exposure to 5 degrees C reduced net rate of glucose metabolism by 15x and net lactate metabolism by 10x as compared with 25 degrees C-exposed tissues. Acclimation to 5 degrees C favored glucose storage as glycogen and increased the proportion of lactate oxidized (versus stored or converted to glucose) when compared with 25 degrees C-acclimated tissues. Net rates of storage of lactate as glycogen (glyconeogenesis) were significantly higher in muscles from 5 degrees C-acclimated frogs during incubation at a common temperature of 15 degrees C. These data suggest that lactate is the predominant fuel for resting skeletal muscle over this temperature range, and particularly so under cold conditions. Ready use of lactate as a substrate, and enhancement of glyconeogenic pathways in response to cold acclimation, could play a role in the tolerance of this species to seasonal temperature changes by promoting sequestration and storage of available substrate under cold conditions.

Accuracy of whole-body low-dose multidetector CT (WBLDCT) versus skeletal survey in the detection of myelomatous lesions, and correlation of disease distribution with whole-body MRI (WBMRI).

AIM: The aim of the study is to assess the feasibility of whole-body low-dose computed tomography (WBLDCT) in the diagnosis and staging of multiple myeloma and compare to skeletal survey (SS), using bone marrow biopsy and whole-body magnetic resonance imaging (WBMRI; where available) as gold standard. MATERIALS AND METHODS: Patients referred over an 18-month period for investigation of suspected multiple myeloma or restaging of myeloma were randomized to undergo one of two WBLDCT protocols using high kVp, low mAs technique (140 kVp, 14 mAs; or 140 kVp, 25 mAs). Recent WBMRI scans were reviewed in 23 cases. Each imaging modality was assessed by two radiologists in consensus and scored from 0-3 (0 = normal, 1 = 1-4 lesions, 2 = 5-20 lesions, 3 >or= 20 lesions/diffuse disease) in ten anatomical areas. Overall stage of disease, image quality score, and the degree of confidence of diagnosis were recorded. Diagnostic accuracy of skeletal survey and WBLDCT were determined using a gold standard of bone marrow biopsy and distribution of disease was compared to WBMRI. RESULTS: Thirty-nine patients were evaluated. WBLDCT identified more osteolytic lesions than skeletal survey with a greater degree of diagnostic confidence and led to restaging in 18 instances (16 upstaged, two downstaged). In those with recent WBMRI, distribution of disease on WBLDCT showed superior correlation with WBMRI when compared with SS. Overall reader impression of stage on WBLDCT showed significant correlation with WBMRI (kappa = 0.454, p < 0.05). WBLDCT provided complementary information to WBMRI in nine patients with normal marrow signal following treatment response, but which were shown to have diffuse residual cortical abnormalities on CT. CONCLUSION: WBLDCT at effective doses lower than previously reported, is superior to SS at detecting osteolytic lesions and at determining overall stage of multiple myeloma, and provides complementary information to WBMRI.

Scaling the duration of activity relative to body mass results in similar locomotor performance and metabolic costs in lizards.

This study examines the physiological response to locomotion in lizards following bouts of activity scaled to body mass. We evaluate this method as a way to compare locomotor energetics among animals of varying body mass. Because most of the costs of brief activity in reptiles are repaid during recovery we focus on the magnitude and duration of the excess post-exercise oxygen consumption (EPOC). Lizards ranging from 3 g to 2400 g were run on a treadmill for durations determined by scaling the run time of each animal to the 1/4 power of body mass and allowing each animal to run at its maximum speed for that duration. This protocol resulted in each species traveling the same number of body lengths and incurring similar factorial increases in V(O(2)). Following activity, EPOC volume (ml O(2)) and the cost of activity per body length traveled (ml O(2) per body length) scaled linearly with body mass. This study shows that the mass-specific costs of activity over an equivalent number of body lengths are similar across a broad range of body mass and does not show the typical patterns of allometric scaling seen when cost of locomotion are expressed on a per meter basis. Under field conditions larger animals are likely to travel greater absolute distances in a given bout of activity than smaller animals but may travel a similar number of body lengths. This study suggests that if locomotor costs are measured on a relative scale (ml O(2) per body length traveled), which reflects these differences in daily movement distances, that locomotor efficiency is similar across a wide range of body mass.

Characterization of circannual patterns of metabolic recovery from activity in Rana catesbeiana at 15 degrees C.

We characterized carbohydrate metabolism following activity in the American bullfrog, Rana catesbeiana, and compared whole body metabolic profiles between two seasons. Forty-eight adult male Rana catesbeiana were chronically cannulated and injected with [U-(14)C]L-lactic acid sodium salt in either summer (June) or winter (January) after acclimation for 2 weeks at 15 degrees C with a 12 h:12 h L:D photoperiod. Following injection with [(14)C]lactate, frogs were either allowed to rest for 240 min (REST), hopped for 2 min on a treadmill and immediately sacrificed (PE), or hopped for 2 min on a treadmill and allowed to recover for 240 min (REC 4). Exercise caused a significant increase in blood lactate level from 2.7+/-0.1 mmol l(-1) at rest to 17.0+/-2.1 mmol l(-1) immediately following exercise. This increase persisted throughout the recovery period, with average blood lactate level only reduced to 13.7+/-1.1 mmol l(-1) after 240 min of recovery, despite complete recovery of intramuscular lactate levels. Lactate levels were not significantly different between seasons in any treatment (REST, PE, REC4), in either gastrocnemius muscle or blood. The vast majority of [(14)C]lactate was recovered in the muscle, in both winter (86.3%) and summer (87.5%). Season had no effect on total amount of (14)C label recovered. [(14)C]Lactate was measured in the forms of lactate, glucose and glycogen, in the liver and the muscle sampled. The most robust difference found in seasonal metabolism was that both the liver and the gastrocnemius contained significantly higher levels of intracellular free glucose under all treatments in winter. These data suggest that, overall, bullfrogs accumulate and slowly clear lactate in a manner quite similar to findings in fish, other amphibians and lizards. Additionally, our findings indicate that lactate metabolism is not highly influenced by season alone, but that intracellular glucose levels may be sensitive to annual patterns.

A comparison of whole-body MRI and CT for the staging of lymphoma.

OBJECTIVE: Our objective was to compare whole-body MRI and CT for the staging of lymphoma. CONCLUSION: Whole-body MRI represents an alternative to CT in the staging of lymphoma, with an ability to stage disease, identify lymph nodes greater than 1.2 cm, and the additional ability to evaluate for the presence or absence of disease spread to bone marrow. CT allows detection of more nodes (< 1.2 cm) than MRI but this does not alter tumor stage.

Metabolic recovery from exhaustive activity by a large lizard.

Gas exchange (VO2 and VCO2) and blood lactate concentration were measured in the lizard Amblyrhynchus cristatus at 25 and 35 degrees C during resting, running, and recovery after exhaustion (less than or equal to 180 min) to analyze the temperature dependency of metabolic recovery in this lizard. Amblyrhynchus exhausted twice as fast (4.2 vs. 8.8 min) at 25 degrees C than when running at the same speed at 35 degrees C. At both temperatures, VO2 and VCO2 increased rapidly during activity and declined toward resting levels during recovery in a manner similar to other vertebrates. Respiratory quotients (R, where R = VCO2/VO2) exceeded 2.0 after exhaustion at both temperatures. Extensive lactate production occurred during activity; blood lactate concentrations ranged from 1.0 to 1.7 mg lactate/ml blood after activity. Net lactate removal exhibited a temperature dependence. Blood lactate concentrations remained elevated hours after VO2 returned to normal. Endurance was reduced in lizards that had recovered aerobically but still possessed high lactate concentrations. The temporal separation of the excess oxygen consumption and lactate removal suggests that the concept of the lactacid oxygen debt is not applicable to this animal. The temperature dependence of total metabolic recovery suggests a benefit for Amblyrhynchus that select warm basking temperatures following strenuous activity.

Post-exercise lactate metabolism: a comparative review of sites, pathways, and regulation.

Most vertebrates utilize supplemental lactate production to support the energetic demands of vigorous, brief exercise. Despite similar patterns of accumulation, there appears to be a trichotomy with regards to lactate processing post-exercise. Most fish retain most of their lactate intramuscularly, using it for in situ glycogen replenishment. Recent evaluation of fish muscle concludes that pyruvate kinase reversal is a probable gluconeogenic pathway. Amphibians and reptiles also utilize lactate as a muscle glyconeogenic substrate, but lactate is not sequestered post-exercise. None of these groups utilize hepatic gluconeogenesis to any significant extent post-exercise, and muscle glucose uptake is limited. Lactate oxidation plays a major role post-exercise in mammals, with hepatic and muscular gluco- and glyconeogenesis contributing to a lesser extent. Glucocorticoids may regulate lactate release from fish muscle, although catecholamines may influence glyconeogenesis in reptile muscle. Insulin affects lactate metabolism indirectly through its effects on muscle glucose metabolism.