Hypercalcemia in association with a Leydig cell tumor in the rat: A model for tumor-induced hypercalcemia in man

The etiology of tumor-induced hypercalcemia was investigated in a transplantable Leydig cell tumor of the Fischer rat. In this model, serum calcium rose from a baseline of 10.4 ± 0.3 m mg/dl to 12.5 ± 0.4 mg/dl at day 10 and 16.4 ± 1.3 mg/dl (p<0.001) at day 13 post transplant. Urinary calcium also increased from 1.52 ± 0.17 mg/d to 3.52 ± 0.72 mg/d (Day 12, p<0.01). Serum phosphate decreased from a baseline of 7.5 ± 0.3 mg/dl to 5.5 ± 0.6 mg/dl at day 13 (p<0.05). At day 13 serum immunoreactive parathyroid hormone levels fell 76% from baseline (p<0.01). Calcitonin increased from 59 ± 2 pg/ml to 88 ± 9 pg/ml (p<0.01). The plasma prostaglandin E metabolite, 13, 14-dihydro-15-keto-PGE₂ increased from 407 ± 103 pg/dl to 647 ± 62 pg/ml (p<0.05) and the active Vit D compound 1, 25(OH)₂D increased from 94.8 ± 5.2 pg/ml to 162.3 ± 11.8 pg/ml (p<0.01). Urinary cyclic AMP did not decrease in parallel with the parathyroid hormone level and, in fact, increased from 146 ± 3 nmol/d to 172 ± 27 nmol/d (NS). Administration of the cyclooxygenase inhibitor indomethacin (20 mg/Kg/d) or hydrocortisone (50 mg/Kg/d) did not prevent the development of hypercalcemia. This model is similar to many patients with humoral hypercalcemia of malignancy who demonstrate suppression of parathyroid hormone with elevated urinary cyclic AMP excretion and may prove useful in the understanding of the responsible mechanisms.     

Effects of a nonperssor analogue of vasopressin on plasma renin activity and salt and water excretion in water-loaded,anesthetized dogs

The object of this study was to determine the importance of vasoconstrictor activity in the suppression of renin secretion by vasopressin. Arginine vasopressin (AVP) (0.05 and 0.1 ng/kg/min) and a nonpressor analogue of vasopressin, 1-deamino-[4-threonine, 8-D-arginine]-vasopressin (dTDAVP) (0.01 and 0.05 ng/kg/min), were infused intravenously in anesthetized hypophysectomized dogs. Neither dTDAVP nor AVP influenced arterial pressure or heart rate but both suppressed plasma renin activity. Infusion of dTDAVP at 0.01 and 0.05 ng/kg/min suppressed plasma renin activity to 86±4% (p<0.05) and 63±6% (p<0.01) of the control values respectively. Infusion of AVP at 0.05 and 0.1 ng/kg/min suppressed plasma renin activity to 60±8% (p<0.01) and 59±12% (p<0.05) of the central values respectively. dTDAVP and AVP both produced significant increases in sodium excretion. These data demonstrate that vasoconstrictor activity is not required for the effects of vasopressin on renin secretion and sodium excretion.     

Mechanism for the increase in plasma renin activity by pentobarbital anesthesia

The mechanism by which pentobarbital anesthesia causes increases in plasma renin activity (PRA) was examined in dogs infused with either propranolol or indomethacin, an inhibitor of prostaglandin synthetase. Infusion of propranolol at 1 mg/kg, (I.V.) followed by 0.6–0.7 mg/kg/hr decreased PRA from 6.98±2.49 ng/m1/hr during control periods to 1.58±0.79 ng/m1/hr 30 minutes after the injection of propranolol (P<0.025). Subsequent induction of anesthesia with sodium pentobarbital caused PRA to rise to 3.87±0.93 ng/m1/hr in 30 minutes. (P<0.01). Plasma potassium concentration decreased from 4.6±0.2 mEq/L to reach 4.0±0.1 mEq/L 30 minutes after induction of anesthesia (P<0.005). Infusion of indomethacin at 5 mg/kg, (I.V.) followed by 1.5 ? 3.1 mg/kg/hr into conscious dogs did not decrease PRA. In contrast to the report by Montgomery et al (Fed. Proc. 36: 989, 1977), we found that the increase in PRA after pentobarbital anesthesia could not be blocked by indomethacin. PRA was 5.3±1.2 ng/m1/hr(M ± SEM) during control periods and was 4.7±1.4 ng/m1/hr 30 minutes after the infusion of indomethacin (P<0.1). PRA increased to 10.9±2.3 ng/m1/hr, 9.2±2.2 ng/m1/hr, and 7.7±1.7 ng/m1/hr at 5, 15 and 30 minutes, respectively, after the administration of pentobarbital (P<0.005, P<0.025, P<0.05). PRA declined to 4.2±1.3 ng/m1/hr 60 minutes after pentobarbital anesthesia (P<0.1). It is concluded that the mechanism by which pentobarbital causes increases in PRA is independent of prostaglandins.     

Alpha melanocyte stimulating hormone inhibits prolactin secretion in fetal and infant lambs

The intravenous administration of αMSH (25 μg/kg) to 11 lambs (3 to 29 days of age) suppressed plasma PRL by 15 minutes. The mean basal concentration was 15.3 ± 2.9 ng/ml and the mean nadir was 4.9 ± 0.8 ng/ml (p<0.01). In chronically catheterized fetuses (128–140 days), intravenous administration of αMSH (25 μg/kg) decreased basal PRL levels (89.6 ± 12.4 ng/ml) significantly at 15–30 minutes to levels of 74.3 ± 11.4 ng/ml (p<.01). The degree of suppression of basal PRL levels was less in fetusus (76.9 ± 4.1%) than that induced in the neonates (40.5 ± 7.1%). In younger fetuses <120 days in whom basal PRL levels are low (3.0 ± 2.1 ng/ml), administration of αMSH was without effect. Plasma GH concentrations were not altered by administration of αMSH. The suppression of PRL secretion by αMSH administration could result from increased release of hypothalamic dopamine or be a direct effect on secretion of prolactin by the pituitary.     

Parathyroid hormone related protein (PTHrP) in patients with pancreatic carcinoma and overt signs of disease progression and host tissue wasting

BackgroundCancer-cachexia is a complex syndrome secondary to physiological mechanisms related to classical hormone and immune alterations, where contributions of neuro-endocrine involvement have been less evaluated. Therefore, the aim of our study was to explore relationships between PTHrP and whole body metabolism in patients with progressive pancreatic carcinoma; relevant to “fat tissue browning”.MethodsPatient serum samples and clinical information were retrieved from earlier translational projects (1995-2005), at Sahlgrenska University Hospital in Gothenburg. Blood PTHrP levels were determined at Harvard medical School (2014). Patient data included: medical history, clinical laboratory tests, food diaries, resting metabolic expenditure, body composition, exercise capacity, Health-Related Quality of Life (SF-36) and mental disorders (HAD-scales).ResultsSerum PTHrP was detectable in 17 % of all samples without significance to tumor stage. PTHrP-negativity at inclusion remained during follow-up. Mean PTHrP concentration was 262±274 pg/ml, without sex difference and elevation over time.PTHrP-positive and negative patients experienced similar body weight loss (%) at inclusion, with a trend to deviate at follow ups (16.8±8.2% vs. 13.1±8.2%, p<0.06), where PTHrP concentrations showed correlations to weight loss, handgrip strength and Karnofsky performance, without difference in exercise capacity.PTHrP-positivity was related to increased whole body fat oxidation (p<0.006-0.01) and reduced carbohydrate oxidation (p<0.01-0.03), independently of peripheral lipolysis. Metabolic alterations in PTHrP-positive patients were related to reduced Health Related Quality of life (SF: p<0.08, MH: p<0.02), and increased anxiety and depression (HAD 1-7: p<0.004; HAD 8-14: p<0.008).ConclusionSerum PTHrP positivity in patients with pancreatic carcinoma was related to altered whole body oxidative metabolism; perhaps induced by “browning” of fat cells?     

Effects of inhibition of prostaglandin-synthesis on renal electrolyte excretion and concentrating ability in healthy man

In five healthy subjects inhibition of prostaglandin (PG)-synthesis with indomethacin did not significantly alter glomerular filtration, urinary flow rate or sodium and potassium excretion during control urine collection periods or i.v. hypertonic saline infusion. Saline administration was accompanied by a fall in urinary PGE₂-excretion from 0.58±0.14 to 0.26±0.09 ng/min (p < 0.05). While indomethacin had no effect on basal urinary osmolality (I_osm),renal concentrating ability following hypertonic saline or i.v. administration of 100 mU lysine-vasopressin significantly increased in the presence of indomethacin with U_osm rising from 805±25 to 970±53 mosm/L (p < 0.01)and from 839±47 to 996±62 mosm/L (p < 0.01),resp. Since this was not accompanied by respective changes in urinary excretion of cyclic adenosine monophosphate (cAMP) mechanisms other than PG-antagonism of vasopressin, such as decreased medullary washout of solute, may contribute to enhanced renal concentrating ability following inhibition of PG-synthesis with indomethacin.     

Evidence from a dual action of converting enzyme inhibitor on blood pressure in normal man

We studied the effect of a converting enzyme inhibitor (CEI), Captopril SQ 14,225 50 mg p.o. in eight supine normal subjects under a high sodium (150 meq/d) and low sodium (25 mEq/d) diet. On high sodium, plasma renin (PRA) and aldosterone were basal and Saralasin did not lower mean blood pressure. However, CEI induced an 11.4±3.2 mm fall in blood pressure (p<0.02) and either indomethacin 50 mg or ibuprofen 800 mg (PI), when given simultaneously on another day, abolished the blood pressure response (2.5±0.9 mm Hg, p>0.5). In contrast, on a low salt diet where renin was increased, CEI induced a drop in blood pressure which was not significantly altered by PI (12.8±1.1 vs. 10.0±3.1 mm Hg, p>0.5). CEI increased plasma renin on both diets (1.7±0.5 to 3.5±0.8 and 2.8±0.6 to 12.5±3.1 ng/ml/hr respectively both p<0.05). Aldosterone did not change (high Na⁺) or fell (low Na⁺). Inhibition of prostaglandin synthesis did not significantly block the renin rise from CEI suggesting that the direct angiotensin II negative feedback is relatively independent of acute prostaglandin release. Our studies suggest that CEI has a dual hypotensive action. In a low renin state, the hypotensive action appears to be mediated through vascular prostaglandins.     

Salt-induced hypertension in chronic renal failure: Evidence for a neurogenic mechanism

We investigated the possibility that blood pressure elevation induced by salt excess may be secondary to a neurogenic mechanism. The compound SK&F 64139 (50 mg/kg) known to inhibit central and peripheral phenylethanolamine N-methytransferase (PNMT) the enzyme necessary for the conversion of norepinephrine to epinephrine, was given by oral gavage to two groups of subtotally nephrectomized rats maintained for five days on either a high salt (HS) or low salt (LS) diet respectively. Blood urea nitrogen (BUN) and hematocrit were not different between the two groups, while body weight and serum Na were significantly higher in the HS animals. Baseline mean blood pressure (BP) was higher in the HS animals (HS 154 ± 4.7 vs LS 121 ± 3.7 mmHg, p<0.001) and decreased by 39 ± 6.9 mmHg one and one half hour post SK&F 64139 to normotensive levels in the HS as opposed to a decrease of 10 ± 1.8 mmHg in the LS group. Baseline heart rate (HR) was higher in the LS group (474 ± 17 beats/min) vs the HS group (408 ± 17, p<0.05), and decreased significantly after SK&F 64139 in both groups to the same extent (by 17.6% in the HS vs 13.3% in the LS). A third group of subtotally nephrectomized rats maintained for five days on a HS diet were given by oral gavage the compount SK&F 29661 (100 mg/kg), a PNMT inhibitor which does not cross the blood-brain barrier. Following SK&F 29661, there was no significant decrease in mean BP (153 ± 5 to 149 ± 4 mmHg) and a less than 2% decrease in HR. Baseline plasma norepinephrine (NE) was higher in the HS as compared to the LS group (1.50 ± 0.16 vs 0.904±0.15 ng/ml, respectively, p<0.05) and a significant correlation was found between plasma NE level and decrease in BP following SK&F 64139 (r=0.65, p<0.01). Not withstanding possible effects of some ancillary properties of SK&F 64139, these data support the hypothesis that a neurogenic component, possibly mediated via central epinephrine containing neurons, contributes to the BP elevation induced by salt excess.     

Renal prostaglandins and sodium balance in normal man

We investigated the relationship between urinary prostaglandin E (PGE) excretion and sodium and water balance. PGE excretion was measured in thirteen healthy male volunteers on the metabolic ward during conditions of high sodium (200 mmols/day) and low sodium diets (40 mmols/day) and during intravenous administration of saline and of dextrose and water, using each subject as his own control. PGE excretion was higher on the high sodium than on the low sodium diet (191±37 SE versus 98±41 ng/6h, p<0.01). Saline and dextrose and water infusions significantly increased PGE excretion while subjects were on low sodium diets (to 314±74 and 443±152 ng/6h, respectively, p<0.01). while on high sodium diets the increase in PGE excretion during infusions was not significant. To further evaluate the role of prostaglandins in sodium excretion the study was repeated with simultaneous administration of indomethacin or ibuprofen to inhibit prostaglandin synthesis. Sodium excretion from saline and dextrose and water infusions were unaltered. The data suggest that dietary content of sodium may alter PGE excretion, but that acute changes in PGE excretion during saline administration reflect water balance rather than sodium load.     

Effect of orlistat on the total ghrelin and leptin levels in obese patients

Obesity, characterized by hyperleptinemia and hypoghrelinemia, has become a major health problem all over the world and is associated with an increased risk of complications including insulin resistance, hypertension, dyslipidemia, diabetes mellitus and atherosclerosis. The use of the pancreatic lipase inhibitor Orlistat can help seriously overweight people to achieve and maintain weight loss. The aim of our study was to compare the serum leptin and ghrelin levels in obese subjects who take orlistat with those receiving only dietary treatment. Twenty-one obese patients and 10 control subjects participated. The obese patients were divided into two groups; one group (n=11) took orlistat (120 mg, 3 times daily) and received dietary treatment and the other (n=10) only received the dietary treatment. The study lasted twelve weeks. The concentrations of serum ghrelin, leptin, insulin and C-peptide, and routine biochemical parameters, were measured in both groups. The serum ghrelin level was higher in control (183±62 fmol/ml) than obese (59±30 fmol/ml) subjects while the plasma leptin level was lower in control (8.7±12 μg/L) than obese (36.7±19 μg/L) subjects (all p<0.001). BMI and the total blood cholesterol, LDL and triglyceride levels fell significantly after both orlistat and dietary treatment in the obese subjects (all p<0.01), and the plasma ghrelin level rose (p<0.01). The leptin level demonstrated the opposite trend in both groups but only the patients taking orlistat showed a significant change (p<0.05).Taken together, these results show that orlistat has no effect on body weight in obese subjects additional to that conferred by a non-pharmacological life-style intervention. We therefore conclude that weight lost rather than type of treatment might be more valuable in obesity.     

The concentration of 6-keto-PGF1α and TXB2 in plasma samples from patients with benign and malignant tumours of the breast

Peripheral plasma concentrations of 6-keto-PGF_1α and TXB₂ were measured in patients with benign and malignant tumours of the breast, in patients with nongynecological disease,a nd in healthy female controls. The values were significantly higher in female patients with maligants tumours of the breast than in healthy controls (146 ± 28 vs 13 ± 2.5 pg/ml for 6-keto-PGF_1α p<0.01 and 78 ± 17 vs 11 ± 2 pg/ml for TXB₂, p<0.01). Benign tumours of the breast were also associated with significantly raised plasma levels of 6-keto-PGF_1α and TXB₂ compared to normal controls (52 ± 5 vs 13 ± 2.5 pg/ml for 6-keto-PGF_1α, p < 0.01 and 26 ± 5 vs 11 ± 2 pg/ml for TXB₂, p < 0.05). The high levels of 6-keto-PGF_1α and TXB₂ were not found to be correlated with clinical and histopathological data. The surgical removal of the primary tumour has apparently no effect on the plasma concentration of 6-keto-PGF_1α and TXB₂ over a follow-up period of 9 days after operation. The lack of alterations in the ratio of TXB₂: 6-keto-PGF_1α in the cancer patients and other subjects studied before and after surgery is indicative of the regulatory power of metabolic systems to preserve the homeostatic balance.     

Dynamic alteration of plasma levels of betatrophin in younger female onset obesity post acute moderate-intensity exercise training

Obesity is a global metabolic disease anchored by a lack of physical activity lipid disturbances. Hitherto, betatrophin is a potential liver-derived hormone that regulates lipid metabolism. A total of 26 selected onset obese individuals (BMI range ± 28–31) were enrolled in this study and given moderate-intensity exercise. Importantly, our data show that acute moderate-intensity interval exercise (MIIE) and acute moderate-intensity continue to exercise (MICE) for 40 min significantly decrease the plasma level of full-length betatrophin respectively (174.18 ± 48.19 ng/mL; 182.31 ± 52.69 ng/mL), compared to the placebo (283.97 ± 32.23 ng/mL) post 10 min and 6 h exercise treatment (p ≤ 0.05). The plasma level of betatrophin was significantly and negatively correlated with BMI (r = ? 0.412, p = 0.037), fasting blood glucose (r = ? 0.390, p = 0.049), and positively correlated with VO_2max (r = 0.456, p = 0.019). In addition, the linear and ordinal logistic regression analysis shows that betatrophin, is a potential predictor for BMI [estimate value = 0.995, p = 0.037 and OR (95 % CI) = 0.992 (0.0984–1.00), p = 0,048]. In summary, our data demonstrate that the circulating levels of betatrophin were decreased after acute moderate-intensity exercise training.     

Forearm electromyographic activity during the deadlift exercise is affected by grip type and sex

Muscle activation, peak velocity (PV) and perceived technical difficulty while using three grip variations and three loads during a deadlift exercise (DL) were examined. Twenty-nine resistance-trained athletes (15 males, age: 22.2 ± 2.7 years; 14 females, age: 24.8 ± 7.0 years) performed the DL with 50%, 70% and 90% of their one repetition maximum (1RM) using hook grip (HG), mixed grip (MG) and double overhand (DOH) grip. Surface electromyography (EMG) of the brachialis (BS), brachioradialis (BR) and flexor carpi ulnaris (FCU) was recorded. PV and perceived technical difficulty of each grip were also measured. Regardless of load and grip, females exhibited greater BS activation compared to males (p < 0.05; ES = 0.69) while males displayed greater BR activation, significant at 90% load (p < 0.01; ES = 1.01). MG elicited the least BR and FCU activation regardless of load and sex (p < 0.01; ES = 0.64–0.68) and was consistently ranked as the easiest grip for any load. Males achieved significantly greater PV than females at 50% and 70% (p < 0.01; ES = 1.72–1.92). Hand orientation did not significantly impact PV. A MG may be beneficial in reducing the overall perceived technical difficulty when performing a maximal DL. Athletes aiming to maximise muscle activation and potentially develop their grip strength should utilise a DOH grip or HG.     

Redistribution of intrarenal blood flow following adh administration: Lack of inhibition by blockade of prostaglandin cyclooxygenase

The effect of prostaglandin synthesis inhibition on the redistribution of renal cortical blood flow in response to antidiuretic hormone (ADH) was examined using radioactive microspheres in water loaded, thiopental-anesthetized dogs. Microsphere injections were made during a control and an ADH infusion period (0.35 mU/kg/min following a 20 mU/kg bolus) both before and after indomethacin pretreatment (8 mg/kg intravenously). Urinary prostaglandin E₂ (PGE₂) excretion in each period was measured by gas chromatography-mass spectrometry. ADH caused a marked redistribution of flow toward inner cortical zones from 19±1 to 25±2 ml/min (mean^± SE, p < 0.01). Fractional flow to inner zones was also significantly increased. Indomethacin pretreatment had no effect on the ADH-induced redistribution (17±2 vs. 24±2 ml/min, p < 0.01), although urinary PGE₂ excretion was suppressed by indomethacin by 60%. It is concluded that prostaglandins do not mediate the redistribution of intrarenal blood flow accompanying ADH administration.     

Reevaluation of circulating prostacyclin and thromboxane in diabetes

Although several investigators have attempted to measure the plasma levels of prostacyclin (PGI₂) and thromboxane A₂ (TXA₂) in diabetes and normal subjects, their results have been controversial. In this study, we measured plasma PGI₂ and TXA₂ levels in diabetic patients and normal subjects. The plasma PGI₂ and TXA₂ were determined by RIA as 6-keto-PGF_1a and TXB₂, respectively. The plasma levels of 6-keto-PGF_1a were significantly reduced in diabetics with microangiopathy (52.5 ± 18.9 pg/ml, mean ± SE, p<0.05) compared with those of normal subjects. Diabetics as a whole also showed lower levels of 6-keto-PGF_1a than normal subjects (57.8 ± 26.1 vs. 70.2 ± 20.7 pg/ml), though this was not significant statistically. The plasma 6-keto-PGF_1a levels did not significantly correlate with either age of the patients or duration of diabetes in diabetics. Interestingly, however, hemoglobin Alc significantly correlated inversely with 6-keto-PGF_1a levels in diabetics without microangiopathy (r=−0.60, p<0.05). The plasma levels of TXB₂ in diabetics were significantly higher than those of normal subjects (155.2 ± 69.5 vs. 108.0 ± 30.0 pg/ml, p<0.05). These data suggest that an imbalance of circulating PGI₂ and TXA₂ may contribute to the development of diabetic microangiopathy.     

Serum Leptin Levels in Obese Males During Over‐ and Underfeeding

Leptin levels in lean adults vary in response to short‐term alterations in energy balance. We tested whether leptin responded to short‐term changes in energy balance in obese males in a similar manner to lean individuals. We enrolled eight obese, healthy males in a 12‐day study composed of four consecutive dietary treatment periods of 3 days each: baseline eucaloric feeding followed by randomized crossover periods of overfeeding (130% of total energy expenditure (TEE)) or underfeeding (70% of TEE), separated by a eucaloric (100% of TEE) washout period. We measured TEE with doubly labeled water prior to baseline. Leptin levels were measured throughout the third day of each treatment and 24‐h weighted averaged were calculated. Subjects' ad libitum intake during a breakfast buffet following each treatment period was recorded. During underfeeding, leptin levels decreased by 21 ± 6% (P < 0.01) from the previous eucaloric period. During overfeeding, leptin levels increased by 25 ± 11% (P < 0.01) when subjects were underfed first, but did not increase (5 ± 8%, nonsignificant (n.s.)) when subjects were overfed first. Changes in ad libitum intake from baseline were calculated for each subject after over‐, under‐, and eucaloric feeding and did not to correlate with the changes in mesor leptin levels from baseline (R² = 0.006, n.s). Leptin levels in obese males were acutely responsive to negative energy balance, but not to positive energy balance unless subjects were previously underfed. Consequently, leptin levels in obese males do not respond to changes in energy intake in a manner that would protect against weight gain.     

The relationship between plasma potassium concentration and muscle torque during recovery following intense exercise

The present study investigated the relationship between plasma potassium ion concentration ([K⁺]) and skeletal muscle torque during three different 15-min recovery periods after fatigue induced by four 30-s sprints. Four males and one female completed the multiple sprint exercise on three separate days; recovery was passive, i.e. no cycling exercise (PRec), active cycling at 30% peak oxygen consumption O_2peak (30% Rec) and active cycling at 60% O_2peak (60% Rec). Plasma [K⁺] was measured from blood sampled from an antecubital vein of subjects at rest and at 0, 3, 5, 10 and 15 min into each recovery. Isokinetic leg strength was measured at rest and at 1, 6, 11 and 16 min during each recovery. Following the exhaustive sprints, [K⁺] increased significantly from an average mean (SEM) resting value of 3.81 (0.07) mmol · l⁻¹ to 4.48 (0.19) mmol · l⁻¹ (P < 0.01). In all recovery conditions, plasma [K⁺] returned to resting levels within 3 min following the fourth sprint. However, in the two active recovery conditions plasma [K⁺] increased over the remainder of the recovery periods to 4.36 (0.12) mmol · l⁻¹ in the 30% Rec condition and 4.62 (0.12) mmol · l⁻¹ in the 60% Rec condition, the latter being significantly higher than the former (P < 0.01). The maximum torque measured following the sprints decreased significantly, on average, to 61.1 (8.36)% of peak levels (P < 0.01). After 15 min of recovery, maximum torque was highest in the 30% Rec condition at 92.13 (3.06)% of peak levels (P < 0.01), compared to 85.23 (3.64)% and 85.71 (0.82)% for the PRec and 60% Rec conditions, respectively. In contrast to the significant differences in plasma [K⁺] across all three recovery conditions, muscle torque recovery was significantly different in only the 30% Rec condition. In summary, recovery of peak levels of muscle torque following fatiguing exercise does not appear to follow changes in plasma [K⁺]. Accepted: 18 October 1996     

Gender Differences in the Response of Plasma Leptin Concentrations to Weight Loss in Obese Older Individuals

Plasma leptin concentration is directly related to the degree of obesity and is higher in women than in men of the same body mass index (BMI). We hypothesized that fasting plasma leptin concentrations and the response of leptin to weight loss would differ in older men and women of a similar fat mass. Plasma leptin concentrations (radioimmunoassay) and fat mass (DXA) were measured in 47 older, obese (BMI=30 ± 4 kg/m²) women and 23 older, obese (BMI=31 ± 3 kg/m²) men after a 2 to 4 week period of weight and dietary stabilization, and then in 22 of the women and 18 of the men after a 6-month weight loss intervention (250–350 kcal/d deficit). Leptin correlated with fat mass in men and women (r=0.75 and r=0.77, respectively; p values<0.0001), but women had 3-fold higher leptin levels for a given fat mass than men (p=0.01). In response to the 6-month hypocaloric diet, men and women lost a similar percentage of fat mass (?13% and ?16%, respectively), but the relative decline in circulating leptin was greater in women than men (-45% and ?21%, respectively; p<0.0001). In addition, when leptin was normalized for fat mass using the ratio method, the decrease in leptin per kilogram of fat mass was greater in women than men (-0.37 ± 0.34 vs. ?0.04 ± 0.06 ng/mL/kg; p<0.01). After weight loss, the change in leptin concentrations correlated positively with the change in fat mass in men (r=0.60; p<0.01), but not in women (r=0.31; p=0.17). Furthermore, the loss in fat mass correlated negatively with baseline leptin levels in women (r=-0.47; p<0.05), but not in men (r=0.03, p=NS). These results indicate that the decline in leptin concentration with weight loss correlates with the loss in fat mass in men; but, in women, other factors affect the decrease in leptin concentration. This suggests that the role of leptin in the regulation of obesity is gender-specific and may account for gender differences in response to hypocaloric treatment and maintenance of lost weight.     

Comparison of the natriuresis and chlorures is associated with glomerular hyperfiltration induced by atrial natriuretic factor or glucagon

The impact on renal sodium chloride reabsorption of an acute increase in glomerular filtration rate (GFR) induced by atrial natriuretic factor (ANF) or glucagon was examined in the conscious rat. These hormones have no direct effect on proximal solute transport and have opposite effects on distal transport. ANF and glucagon increased GFR to a comparable extent (2.0 ± 0.2 to 3.5 ± 0.4 ml/min, p<0.01, and 1.9 ± 0.1 to 3.3 ± 0.1 ml/min, p<0.001, respectively). While most (95–97%) of the increment in filtered sodium chloride was reabsorbed, a small portion (3–5%) escaped tubular reabsorption. Absolute sodium and chloride urinary excretion rates increased similarly in response to each hormone, by two- to three-fold. Slightly imperfect load-dependent sodium chloride reabsorptive response by the nephron, despite opposite direct effects on distal nephron transport, may account for the observed natriuresis and chloruresis associated with the acute glomerular hyperfiltration induced by ANF or glucagon administration.     

Left ventricular assist device: a functional comparison with heart transplantation

Background A growing number of patients with end-stage heart failure undergo implantation of ventricular assist devices as a bridge to heart transplantation. Objectives In this study we investigated whether functional and haemodynamic recovery after implantation is sufficient to warrant the use of them as long-term alternative to heart transplantation. Methods We compared peak VO₂ of a group of patients three months after implantation of a ventricular assist device and three months after heart transplantation. Furthermore, we analysed the degree of haemodynamic recovery, by comparing plasma levels of BNP and creatinine before and after implantation of the device. Results After implantation of a ventricular assist device, exercise capacity improved considerably; three months after implantation peak VO₂ was 20.0±4.9 ml/kg/min (52% of predicted for age and gender). After heart transplantation exercise capacity improved even further; 24.0±3.9 ml/ kg/min (62% of predicted for age and gender) (p<0.001). In the three months after implantation, BNP plasma levels decreased from 570±307 pmol/l to 31±25 pmol/l and creatinine levels decreased from 191±82 μmol/l to 82±25 μmol/l, indicating significant unloading of the ventricles and haemodynamic recovery. Conclusion With regard to functional and haemodynamic recovery, the effect of implantation of a ventricular assist device is sufficient to justify its use as an alternative to heart transplantation. (Neth Heart J 2008;16:41-6.)