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There are several key points clinicians should consider when managing patients with overlapping thyroid and renal disease. Patients who are euthyroid and have chronic kidney disease (CKD) may physiologically have normal-high thyroid stimulating hormone (TSH), low free thyroxine (FT4), low free triiodothyronine (FT3) and normal-low reverse triiodothyronine (rT3). Untreated subclinical and primary hypothyroidism among patients with (CKD) is associated with reversible progression of renal failure. Supplementing these (CKD) patientswith levothyroxine can delay the progression of renal failure and prevent end stage renal disease (ESRD). Untreated hyperthyroidism increases the glomerular filtration rate (GFR) by 18 to 25%. Thus, the management of hyperthyroidism may unmask patients with undiagnosed CKD. There is no dosage adjustment required for methimazole among patients with CKD. However, methimazole may be eliminated during hemodialysis (HD) by around 30 to 40%. Patients with papillary thyroid cancer and ESRD may have higher rates of aggressive characteristics. Patients with CKD and ESRD undergoing radioiodine I-131 treatment for thyroid cancer are at increased risk of prolonged radiation transmission risk due to decreased iodine urinary excretion. Additionally, the optimal dosing and timing of radioiodine I-131 therapy amongst patients with ESRD and thyroid cancer requires further research. The use dosimetry studies and multidisciplinary coordination among nuclear medicine, nephrology and endocrinology is recommended for these patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Inc.)

Type 2 diabetes is a heterogeneous disease with multiple underlying pathophysiological processes. Several new antidiabetic agents are presently available for clinical use, yet very few clinical trials have been performed on the efficacy of combination pill therapy. Combination pill use is easily justified as a second-line therapy in which the advantages of added efficacy, enhanced adherence, and only modest increase in risk are recognized. In contrast, combination pill use as first-line therapy has some drawbacks, such as increased risk of hypoglycemia, difficulty in attribution of side effects to the constituents, and less than additive efficacy of the components of the pill. In general, combinations of drugs with synergistic mechanisms of action are preferable. However, the efficacy of currently available combination pills when used as first-line therapy is less than the sum of the efficacy of its components. The current guidelines recommend initiation of dual therapy in drug-naive individuals depending on baseline HbA1c at the time of diagnosis. When the HbA1c is above 8.5%-9%, the likelihood of achieving glycemic targets with a single agent diminishes sharply. These patients may be better candidates for treatment with a combination of antihyperglycemic agents as first-line therapy.

Pulmonary hernia is a protrusion of lung tissue through a defect in the chest wall. Its origin can be congenital or acquired; spontaneous presentation is the least frequent. We report a case of spontaneous intercostal pulmonary hernia with a brief description of the disease. In this case, the patient developed a hematoma in the left hemithorax associated to pain at the base of the left hemithorax after a Valsalva's maneuver. The images obtained by thoracic CT scan revealed the existence of a left intercostal hernia. After radiological diagnosis, surgical treatment of the defect was performed with good results.

Study Objective: To determine whether transversus abdominis plane (TAP) blocks administered in conjunction with intrathecal morphine provided superior analgesia to intrathecal morphine alone., Design: Randomized, double-blind, placebo-controlled study., Setting: Operating room of a university hospital., Patients: 51 women undergoing elective Cesarean delivery with a combined spinal-epidural technique that included intrathecal morphine., Interventions: Subjects were randomized to receive a bilateral TAP block with 0.5% ropivacaine or 0.9% saline. Postoperative analgesics were administered on request and selected based on pain severity., Measurements: Patients were evaluated at 2, 24, and 48 hours after the TAP blocks were performed. Verbal rating scale (VRS) pain scores at rest, with movement, and for colicky pain were recorded, as was analgesic consumption. Patients rated the severity of opioid side effects and their satisfaction with the procedure and analgesia., Main Results: 51 subjects received TAP blocks with ropivacaine (n = 26) or saline (n = 25). At two hours, the ropivacaine group reported less pain at rest and with movement (0.5 and 1.9 vs 2.8 and 4.9 in the saline group [VRS scale 0 - 10]; P < 0.001) and had no requests for analgesics; there were several requests for analgesia in the saline group. At 24 hours, there was no difference in pain scores or analgesic consumption. At 48 hours, the ropivacaine group received more analgesics for moderate pain (P = 0.04) and the saline group received more analgesics for severe pain (P = 0.01)., Conclusions: Transversus abdominis plane blocks in conjunction with intrathecal morphine provided superior early postcesarean analgesia to intrathecal morphine alone. By 24 hours there was no difference in pain scores or analgesic consumption., (© 2013 Elsevier Inc. All rights reserved.)

Dyslipidemia is one of the key risk factors for cardiovascular disease (CVD) in diabetes mellitus. Despite the mounting clinical trial data, the management of dyslipidemia other than lowering the low density lipoprotein cholesterol (LDL-c) continues to be controversial. The characteristic features of diabetic dyslipidemia are high plasma triglyceride concentration, reduced high density lipoprotein cholesterol (HDL-c) concentration, and increased concentration of small dense LDL particles. These changes are caused by increased free fatty acid flux secondary to insulin resistance and aggravated by increased inflammatory adipokines. The availability of several lipid-lowering drugs and nutritional supplements offers novel and effective options for achieving target lipid levels in people with diabetes. While initiation of drug therapy based on differences in the lipid profile is an option, most practice guidelines recommend statins as first-line therapy. Although the evidence for clinical utility of combination of statins with fibrates or nicotinic acid in reducing cardiovascular events remains inconclusive, the preponderance of evidence suggests that a subgroup who have high triglycerides and low HDL-c levels may benefit from combination therapy of statins and fibrates. The goal of therapy is to achieve at least 30-40 % reduction in LDL-c levels. Preferably the LDL-c should be less than 100 mg/dL in low-risk people and less than 70 mg/dL in those at high risk, including people with established CVD.

Objective: Diabetic dyslipidemia is an important risk factor for the development of macrovascular complications. Recent clinical trials suggest that diabetics treated with glucagon-like peptide-1 (GLP-1) have normalized lipid levels, including an increase in plasma high-density lipoprotein cholesterol (HDLc) levels., Methods: To determine if GLP-1 (7-36 amide) and the GLP-1-like insulinotropic peptide exendin-4 regulate expression of apolipoprotein A-I (apo A-I), the primary anti-atherogenic component of high-density lipoprotein (HDL), HepG2 hepatocytes and Caco-2 intestinal cells, representative of tissues that express the majority of apo A-I, were treated with increasing amounts of each peptide and apo A-I gene expression was measured in the conditioned medium., Results: Apo A-I secretion increased in both GLP-1 and exendin-4-treated HepG2, but not Caco-2 cells, and this was accompanied by similar changes in apo A-I mRNA levels and apo A-I promoter activity. Induction of apo A-I promoter activity by GLP-1 and exendin-4 required an SP1-responsive element. Hepatic ATP binding cassette protein A1 (ABCA1) expression, but not scavenger receptor class B type1 receptor expression was also induced by GLP-1 and exendin-4., Conclusions: These results suggest that GLP-1- and exendin-4-mediated changes in HDLc are likely due to changes in hepatic expression of apo A-I and ABCA1., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The prevalence of diabetes mellitus increases with age and causes significant morbidity and poor quality of life in older adults. To review the current literature on the diagnosis and management of diabetes in the elderly, the relevant manuscripts were identified through a MEDLINE (2000-September 1, 2010) search of the English literature. The key phrase used was diabetes in older adults or diabetes in the elderly. The literature search was limited to core clinical journals that have accessible full texts. A total of 480 manuscripts were reviewed. Managing diabetes in older adults is a challenging task. Some features of the disease are unique to the older patient. Several new antidiabetic agents are now available for clinical use, and yet very few clinical trials have been carried out in this age group. For many older adults, maintaining independence is more important than adherence to published guidelines to prevent diabetes complications. The goals of diabetes care in older adults are to enhance quality of life without subjecting the residents to inappropriate interventions.

The objective was to test the effect of nicotinic acid on apolipoprotein A-I (apo A-I) gene expression in hepatic (HepG2) and intestinal (Caco-2) cell lines. HepG2 and Caco-2 cells were treated with 0.1, 0.3, 1.0, 3.0, and 10 mmol/L of nicotinic acid; and apo A-I concentrations in conditioned media were measured with Western blots. Relative apo A-I messenger RNA (mRNA) levels, normalized to glyceraldehyde-3-phosphate dehydrogenase mRNA, were measured with quantitative real-time polymerase chain reaction method. The nicotinic acid response element in the apo A-I promoter was identified using a series of apo A-I reporter plasmids containing deletion constructs of the promoter. In other experiments, HepG2 cells were also transfected with the apo A-I reporter plasmid and the hepatocyte nuclear factors 3α and β expression plasmids. The apo A-I levels in conditioned media from HepG2 cells, apo A-I mRNA levels, and apo A-I promoter activity increased significantly following treatment with 1.0, 3.0, and 10 mmol/L nicotinic acid. Nicotinic acid-induced promoter activity required a region of the apo A-I gene located between -170 and -186 base pairs. Exogenous overexpression of the hepatocyte nuclear factors 3α and β had no additive effect on apo A-I promoter. Apolipoprotein A-I concentrations in conditioned media and the apo A-I promoter activity were also significantly increased in Caco-2 intestinal cells. Nicotinic acid may increase apo A-I protein synthesis in the liver and small intestine. Induction of apo A-I gene by nicotinic acid requires a nicotinic acid responsive element in the apo A-I promoter.

Background: The intercristal line is known to most frequently cross the L4 spinous process or L4-5 interspace; however, it is speculated to be positioned higher during pregnancy because of the exaggerated lumbar lordosis. Clinical estimation of vertebral levels relying on the use of the intercristal line has been shown to often be inaccurate. We hypothesized that the vertebral level of the intercristal line determined by palpation would be higher than the level determined by ultrasound in pregnant women., Methods: Fifty-one term pregnant patients were recruited. Two experienced anesthesiologists performed estimates of the position of the intercristal line by palpation. Using ultrasound, another anesthesiologist who was blinded to the clinical estimates, determined the position of the superior border of the iliac crest in the transverse and longitudinal planes and then identified the lumbar vertebral levels. The vertebral level at which the clinical estimates of the intercristal line crossed the spine was recorded and compared with the ultrasound-determined level of the superior border of the iliac crest., Results: The clinical estimates of the spinal level of the intercristal line agreed with the ultrasound measurement 14% of the time (14 of 101; 95% confidence interval [CI]: 8%, 22%). The clinical estimates were 1 level higher than the ultrasound measurement 23% of the time (23 of 101; 95% CI: 16%, 32%) and >1 level higher 25% of the time (25 of 101; 1-tailed 95% CI: >18%). The distribution of the clinical estimates found clinicians locating the intercristal line at L3 or L3-4 54% of the time (54 of 101; 95% CI: 44%, 63%) and at L2-3 or higher 27% of the time (27 of 101; 1-tailed 95% CI: >20%)., Conclusion: The anatomical position of the intercristal line was at L3 or higher in at least 6% of term pregnant patients using ultrasound. Clinical estimates were found to be ≥1 vertebral level higher than the anatomical position determined by ultrasound at least 40% of the time. This disparity may contribute to misidentification of lumbar interspaces and increased risk of neurologic injury during neuraxial anesthesia.

There is ample empiric evidence to indicate that oxidative stress contributes to the pathogenesis of coronary artery disease and has a key role in the onset and progression of diabetes and its complications. Diabetes leads to depletion of the cellular antioxidant defense system and is associated with an increase in the production of free radicals. Oxidative stress can be the result of multiple pathways. Some of these are related to substrate-driven overproduction of mitochondrial reactive oxygen species, advanced glycation end product formation, glucose autoxidation, and depletion of micronutrients and cellular elements with antioxidative properties. There are numerous observational studies in the literature showing a beneficial outcome of the consumption of antioxidant vitamins. However, the interventional trials portray a different picture. The divide between the robust experimental evidence of the pathogenetic role of increased oxidative load in diabetes and the overwhelming failure of antioxidants to show any health benefits in clinical trials may well be characterized as the "antioxidant paradox."

Background: The importance of optimising blood glucose (BG) control in hospitalised patients is widely accepted. To determine whether focused education of physicians and nurses would result in measurable changes in glycaemic control, the effect of a diabetes-focused educational programme on point of care (POC) BG measures was monitored., Methods: This programme included 2 h symposium and 2 h interactive session. The POC BG measures were determined at 2-month period prior to implementing the programme and the ensuing 7 months after. Outcome parameters included the mean BG values, the incidence of hyperglycaemia (BG > 180 mg/dl) and hypoglycaemia (BG < 60 mg/dl). The outcome parameters were analysed by comparing the Internal Medicine (target service) to other such as Neurology and Surgical Trauma where no programme was offered., Results: On Internal Medicine, the mean BG decreased soon after implementing the programme and stayed lower than the baseline values over 7 months. The changes were significant at the third, fourth, seventh and the ninth month of the study. Hyperglycaemia decreased significantly (p < 0.05) on the third, fourth, seventh and eighth month, while hypoglycaemia increased following the education programmes. On Neurology and Surgical Trauma, the mean BG values were significantly higher, and hypoglycaemia was significantly lower during the same time frame., Conclusions: Implementing an educational programme for healthcare providers had significant effects on the lowering of mean BG values and the incidence of hyperglycaemia, but increased the risk of hypoglycaemia. The merits of such programmes need to be tested before their widespread implementation.

Study Objective: To investigate the efficacy of preoxygenation by eight deep breaths in 60 seconds with the Mapleson A (Magill) system, the circle anesthesia system, or the Mapleson D system at an oxygen flow of 5 L/min or 10 L/min., Design: Randomized, clinical study., Setting: Operating room of a university hospital., Subjects: 10 healthy volunteers., Interventions: Volunteers underwent 6 preoxygenation trials consisting of 8 deep breaths in 60 seconds using the Mapleson A, Mapleson D, and the circle anesthesia systems at an oxygen flow of 5 L/min and 10 L/min., Measurements: Fractional end-tidal oxygen concentration (F(ET)O(2)) was measured at 15-second intervals during preoxygenation., Results: At an oxygen flow of 10 L/min, mean F(ET)O(2) values at 60 seconds of preoxygenation were comparable among the Mapleson A, Mapleson D, and the circle anesthesia systems (87 +/- 2.1%, 87 +/- 1.6%, 87 +/- 1.6%, respectively). Using an oxygen flow of 5 L/min, mean F(ET)O(2) values at 60 seconds were similar among the Mapleson A, Mapleson D, and circle anesthesia systems (74 +/- 4.1%, 75 +/- 2.6%, 74 +/- 4.4%, respectively); however, they were significantly lower than the corresponding values achieved at an oxygen flow of 10 L/min., Conclusions: The 8-deep-breaths in 60 seconds technique at an oxygen flow of 10 L/min can achieve adequate preoxygenation with the Mapleson A (Magill), Mapleson D, and circle anesthesia systems. Suboptimal preoxygenation is obtained with the three systems when the oxygen flow used is 5 L/min.

During apnoea following induction of anaesthesia, morbidly obese patients may suffer a rapid decrease in oxygen saturation. This study compares pre-oxygenation alone with pre-oxygenation followed by nasopharyngeal oxygen insufflation on the onset of desaturation occurring during the subsequent apnoea. A randomised controlled trial was performed in 34 morbidly obese patients undergoing gastric bypass or gastric band surgery. Seventeen patients received nasopharyngeal oxygen supplementation following pre-oxygenation (Study group, body mass index = 41.8 (6.9) kg.m(-2)), and the other 17 patients received pre-oxygenation alone (Control group, body mass index = 42.7 (5.4) kg.m(-2)). Time from the onset of apnoea until S(p)o(2) fell to 95% was compared between the two groups with a cut-off of 4 min. In the control group, the S(p)o(2) fell from 100% to 95% during the subsequent apnoea in 145 (27) s, with a significantly negative correlation (r(2) = 0.66, p < 0.05) between the time to desaturation to 95% and the body mass index. In the study group, the S(p)o(2) was maintained in 16 of 17 patients at 100% for 4 min when apnoea was terminated. In conclusion, nasopharyngeal oxygen insufflation following pre-oxygenation in morbidly obese patients delays the onset of oxyhaemoglobin desaturation during the subsequent apnoea.

Purpose: This study investigates the efficacy of preoxygenation with Mapleson A and Mapleson D breathing systems vs the circle system with CO2 absorber., Methods: Thirteen healthy volunteers underwent tidal volume breathing for three minutes via facemask using Mapleson A, Mapleson D breathing systems or the circle system with CO2 absorber while breathing 100% O2 at flow rates of 5 L.min-1 and 10 L.min-1. Each volunteer acted as his/her own control by going through each of six preoxygenation protocols in random order. Fractional end-tidal O2 concentration (FETO2) was measured at 30-sec intervals. The results were compared among the three anesthesia systems at the two fresh gas flow rates., Results: At a fresh gas flow rate of 5 L.min-1, the Mapleson A and circle systems achieved F(ETO2) values of 90.8+/-1.4% and 90.0+/-1.1%, respectively, compared with the lower F(ETO2) (81.5+/-6.3%, P<0.05), achieved with the Mapleson D system. When breathing O2 at 10 L.min-1, the F(ETO2) values after three minutes were similar with the Mapleson A, circle, and Mapleson D breathing systems (91.8+/-2.3%, 91.2+/-1.7%, 90.6+/-2.7%, respectively)., Conclusion: When using the Mapleson A and the circle systems for preoxygenation, an oxygen flow rate of 5 L.min-1 can adequately preoxygenate the patient within three minutes, while an oxygen flow of 10 L.min-1 is required to achieve a similar fractional end-tidal O2 concentration with the Mapleson D system.

The endothelial or epithelial tight junctions create a rate-limiting barrier to diffusion of solutes. A major determinant of the barrier function is the density of tight junction proteins. Since aging is associated with significant alterations in the blood-brain barrier (BBB) it is possible that specific tight junction proteins may be altered in the cerebrum of aging rats. To test this hypothesis, Western and Northern blot analysis were carried out to measure the steady-state level of occludin and zonula occludens-one (ZO-1) proteins and their mRNA in cerebral tissue of 3-, 12- and 24-month-old rats. The cerebral occludin content in 24-month-old rats (732.5+/-99.9 arbitrary units) was significantly reduced compared to 12-month-old rats (1043.4+/-131.8) or 3-month-old rats (1021.4+/-62.8), P<0.01. The cerebral ZO-1 protein content in 24-month-old rats (161.7+/-8.1 arbitrary units) and 12-month-old rats (144.3+/-35.9) were not significantly reduced compared to 4-month-old rats (189.0+/-27.2). The occludin mRNA content relative to G3PDH mRNA was 1.11+/-0.05, 1.11+/-0.07 and 1.00+/-0.05 in 3-, 12- and 24-month-old rats, respectively. The differences did not achieve statistical significance. The ZO-1 mRNA content of cerebral tissue relative to G3PDH mRNA was significantly increased in 24-month-old rats compared to 3-month-old rats (1.280+/-0.030 vs. 0.956+/-0.038), P<0.001. It is concluded that aging in rats may alter the molecular anatomy of the BBB by altering the content of select structural proteins of tight junctions.

The endothelial or epithelial tight junctions create a barrier to diffusion of solutes. Since experimental diabetes mellitus is associated with considerable alterations in the blood-brain barrier (BBB), it is possible that specific tight junction proteins may be altered in diabetes. To test this hypothesis, Western and Northern blot analysis were carried out to measure the steady-state level of occludin and zonula occludens-one (ZO-1) proteins and mRNA levels in cerebral tissue of streptozotocin-induced diabetic rats and the results were compared to insulin treated diabetic rats and vehicle injected control rats. The cerebral occludin content in diabetic rats (115.4 +/- 18.6 arbitrary units) was significantly reduced compared to insulin-treated diabetic rats (649.1 +/- 141.2) or control rats (552.9 +/- 82.9), p < 0.001. The ZO-1 content of cerebral tissue from diabetic rats (1,240.6 +/- 199.7 arbitrary units) was not significantly altered compared to controls (1,310.8 +/- 256.9). The cerebral occludin mRNA content relative to G3PDH mRNA was 1.35 +/- 0.07 and 1.34 +/- 0.19 in control and diabetic rats respectively. The cerebral ZO-1 mRNA content relative to G3PDH mRNA in diabetic and control rats was 1.135 +/- 0.123 and 0.956 +/- 0.038 respectively. These differences did not achieve statistical significance. It is concluded that diabetes alters the molecular anatomy of the tight junctions in cerebral tissue by altering the content of select structural proteins.

Objective: To determine the role of repeated fine-needle aspiration (FNA) biopsy in the evaluation of thyroid nodules initially classified as benign., Methods: We retrospectively reviewed data on 235 patients with clinically palpable thyroid nodules who underwent a repeated FNA biopsy after an initially benign diagnosis. All the nodules were evaluated and biopsies were obtained by the same endocrinologist. Cytodiagnoses were divided into four major categories: inadequate, benign, suspicious, or malignant., Results: The study cohort consisted of 211 female and 24 male patients with a mean age of 47.1 years. The repeated FNA cytodiagnoses were as follows: 204 (86.8%) remained benign and 19 (8.1%), 11 (4.7%), and 1 (0.4%) became inadequate, suspicious, and malignant, respectively. All patients with benign or inadequate cytologic results on repeated FNA who underwent thyroid surgical resection had benign histologic findings (N = 23). The mean follow-up period between the initial and the last benign FNA cytodiagnosis in the 186 patients without surgical intervention was 1,078 days (2.95 years). Nine of 11 patients with suspicious cytologic results underwent a thyroid surgical procedure, which revealed a benign lesion in 7 and malignant disease in 2 (18%). The other two patients with suspicious cytologic findings had a 13-year clinical follow-up without any clinical evidence of a thyroid malignant lesion. The only patient with malignant cytologic findings on repeated FNA (a 76-year-old woman) refused surgical treatment and was lost to follow-up., Conclusion: Although the yield of finding a malignant lesion on repeated FNA biopsy in the follow-up of a presumably benign thyroid nodule may be low, rebiopsy reduces the rate of false-negative diagnosis from an average of 5.2% to <1.3%.

Several new pharmacological agents have recently been developed to optimise the management of type 2 (non-insulin-dependent) diabetes mellitus. The aim of this article is to briefly review the various therapeutic agents available for management of patients with type 2 diabetes mellitus and to suggest a potential approach to drug selection. There are three general therapeutic modalities relevant to diabetes care. The first modality is lifestyle adjustments aimed at improving endogenous insulin sensitivity or insulin effect. This can be achieved by increased physical activity and bodyweight reduction with diet and behavioural modification, and the use of pharmacological agents or surgery. This first modality is not discussed in depth in this article. The second modality involves increasing insulin availability by the administration of exogenous insulin, insulin analogues, sulphonylureas and the new insulin secretagogue, repaglinide. The most frequently encountered adverse effect of these agents is hypoglycaemia. Bodyweight gain can also be a concern, especially in patients who are obese. The association between hyperinsulinaemia and premature atherosclerosis is still a debatable question. The third modality consists of agents such as biguanides and thiazolidinediones which enhance insulin sensitivity, or agents that decrease insulin requirements like the alpha-glucosidase inhibitors. Type 2 diabetes mellitus is a heterogeneous disease with multiple underlying pathophysiological processes. Therapy should be individualised based on the degree of hyperglycaemia, hyperinsulinaemia or insulin deficiency. In addition, several factors have to be considered when prescribing a specific therapeutic agent. These factors include efficacy, safety, affordability and ease of administration.

To determine if aging is associated with altered serum leptin response to diet-induced changes in endogenous hyperinsulinemia, male Fisher 344 (F344) rats at different age groups were studied while on regular rat chow and following 10 days of experimental diets consisting of 60% of the weight as fructose or glucose. The serum leptin concentration (ng/ml) gradually increased from basal levels of 2.5+/-0.1 at age of 4 months to 3.7+/-0.1, 6.9+/-0.9, 9. 4+/-0.3 and 8.9+/-1.1 at 6, 12, 18 and 24 months of age, respectively (P<0.001). Hyperinsulinemia associated with 60% fructose diet was associated with increased serum leptin levels in 4, 12, and 24 month old rats to 5.1+/-0.8, 6.7+/-1.2, and 8.6+/-1.1, respectively (P<0.001). Feeding 60% glucose diet also was associated with increased serum leptin levels in 4, 12 and 24 month old rats to 7.6+/-0.6, 7.2+/-0.7, and 9.1+/-1.1, respectively (P<0.001). Restricting dietary intake to 60% of the calories consumed by control rats for 10 days resulted in a decrease in serum leptin to 1.0+/-0.02 in 4 month old rats and 2.5+/-0.4 in 24 month old rats (P<0.01). It is concluded that aging in F344 rats is associated with increased serum leptin concentrations. However, diet-related hyperinsulinemic effect on leptin is blunted in aging rats although leptin response to caloric restriction is maintained. The inability of aging rats to mount hyperleptinemic response to dietary changes may contribute to the age-related increase in adiposity.

To determine the age-related changes in thyroid hormone (TH) effects on cardiac glucose transporter one (GLUT-1) and four (GLUT-4) isoforms, male Fischer 344 rats at 4, 12, and 25 months of age were studied at euthyroid, hyperthyroid and hypothyroid conditions. Hyperthyroidism was induced with daily intraperitoneal injections of triiodothyronine (15 microg/100 gm) for 10 days. Hypothyroidism was achieved with 0.025% methimazole in the drinking water for 4 weeks. Immunoblot analysis indicated that at euthyroid basal conditions GLUT-1 protein was not significantly altered with age while GLUT-4 protein was significantly reduced in 25 month old rats (82.0 +/- 28.8% of a 4 month old rat p <0.01). In 4 months old rats, GLUT-1 was increased in both hypothyroidism (432.5 +/- 208.7% of age-matched euthyroid control) and to a lesser extent in hyperthyroidism (242.0 +/- 93.3% of control) p<0.01. In 25 month old rats, hyperthyroidism was also associated with increased GLUT-1 mass (190.8 +/- 117.6% of age-matched euthyroid control) p<0.01. Hypothyroidism in this age group was not associated with significant change in GLUT-1 protein. The cardiac GLUT-4 protein was increased during both hypothyroidism and hyperthyroidism. The changes of GLUT-4 in aged rats were similar to those found in young rats. It is concluded that TH effect on GLUT-1 expression in the heart is altered with age while TH effects on GLUT-4 are age independent.