Nocturnal increase in plasma cGMP levels in humans.

The circadian dynamics of responses to cyclic guanosine 3',5'-monophosphate (cGMP) in in vitro experiments and the stimulating effects of the pineal hormone melatonin on cGMP levels both in vitro and in vivo provoked an investigation into the diurnal pattern of occurrence of this second messenger in human plasma and its correlation with plasma melatonin levels. Plasma cGMP levels were measured in 9 normal human subjects who were over 50 years of age. Samples were obtained hourly through a 20-h period (11 a.m. to 7 a.m.) that included the subjects' habitual hours of nocturnal sleep; physical activity was kept to a minimum during the daylight hours. The area under the time-plasma cGMP concentration curve showed a significant increase during the period of nocturnal sleep compared to that observed during the period of daytime wakefulness. The individual temporal pattern of the nocturnal rise in plasma cGMP differed among the subjects; however, the initial increase typically was observed soon after bedtime. No significant correlation was observed between individual nocturnal plasma melatonin levels and cGMP levels.     

Detection of transient capacitance increase associated with channel formation in lipid bilayers.

The insertion of alpha- and beta-latrotoxins and sea anemone (Radianthus macrodactilus) toxin into bilayer lipid membranes (BLMs) was investigated using the method of simultaneous conductance/capacitance measurement. All the toxins investigated induced capacitance changes which preceded toxin-induced conductance increases. The processes that may underlie the observed effect are discussed.     

Human genetic affinities for Y-chromosome P49a,f/TaqI haplotypes show strong correspondence with linguistics.

Numerous population samples from around the world have been tested for Y chromosome-specific p49a,f/TaqI restriction polymorphisms. Here we review the literature as well as unpublished data on Y-chromosome p49a,f/TaqI haplotypes and provide a new nomenclature unifying the notations used by different laboratories. We use this large data set to study worldwide genetic variability of human populations for this paternally transmitted chromosome segment. We observe, for the Y chromosome, an important level of population genetics structure among human populations (FST = .230, P < .001), mainly due to genetic differences among distinct linguistic groups of populations (FCT = .246, P < .001). A multivariate analysis based on genetic distances between populations shows that human population structure inferred from the Y chromosome corresponds broadly to language families (r = .567, P < .001), in agreement with autosomal and mitochondrial data. Times of divergence of linguistic families, estimated from their internal level of genetic differentiation, are fairly concordant with current archaeological and linguistic hypotheses. Variability of the p49a,f/TaqI polymorphic marker is also significantly correlated with the geographic location of the populations (r = .613, P < .001), reflecting the fact that distinct linguistic groups generally also occupy distinct geographic areas. Comparison of Y-chromosome and mtDNA RFLPs in a restricted set of populations shows a globally high level of congruence, but it also allows identification of unequal maternal and paternal contributions to the gene pool of several populations.     

Angptl3-null mice show low plasma lipid concentrations by enhanced lipoprotein lipase activity.

Angiopoietin-like 3 (ANGPTL3) is a secreted protein with both angiogenesis and lipid metabolism functions. We generated knockout mice that failed to express the Angptl3 gene, and analyzed the lipid metabolism. Angptl3-null mice, fed a normal diet or a high-fat, high-calorie (HFC) diet, revealed markedly low plasma lipid concentrations, especially plasma triglyceride concentration, although the body weight and liver weight were not different between Angptl3-null mice and wild-type mice. Angptl3-null mice fed an HFC diet also revealed a significantly reduced epididymal adipose tissue weight despite there being no difference in adipocyte size between them and wild-type mice. A triglyceride clearance study indicated that the lower plasma triglyceride concentration in Angptl3-null mice was caused by an accelerated clearance of triglyceride. In fact, lipoprotein lipase and hepatic lipase activities in the post-heparin plasma of Angptl3-null mice were 1.57 times and 1.42 times higher than those of wild-type mice, respectively. These results suggest that ANGPTL3 may have an effect not only on lipid metabolism but also on adipose formation.     

Mechanism for the posture-specific plasma volume increase after a single intense exercise protocol.

To test the hypothesis that exercise-induced hypervolemia is a posture-dependent process, we measured plasma volume, plasma albumin content, and renal function in seven healthy subjects for 22 h after single upright (Up) or supine (Sup) intense (85% peak oxygen consumption rate) exercise. This posture was maintained for 5 h after exercise. Plasma volume decreased during exercise but returned to control levels by 5 h of recovery in both postures. By 22 h of recovery, plasma volume increased 2.4 +/- 0.8 ml/kg in Up but decreased 2.1 +/- 0.8 ml/kg in Sup. The plasma volume expansion in Up was accompanied by an increase in plasma albumin content (0.11 +/- 0.04 g/kg; P < 0.05). Plasma albumin content was unchanged in Sup. Urine volume and sodium clearance were lower in Up than Sup (P < 0.05) by 5 h of recovery. These data suggest that increased plasma albumin content contributes to the acute phase of exercise-induced hypervolemia. More importantly, the mechanism by which exercise influences the distribution of albumin between extra- and intravascular stores after exercise is altered by posture and is unknown. We speculate that factors associated with postural changes (e.g., central venous pressure) modify the increase in plasma albumin content and the plasma volume expansion after exercise.     

Post-exercise increase of lipid oxidation after a moderate exercise bout in untrained healthy obese men.

The aim of the study was to examine whether a moderate exercise increases the utilization of fatty acids during the recovery period in obese men. Six healthy obese participated in a randomized crossover investigation, one with exercise and one without exercise. At 8 a. m., the subjects had a standardized breakfast and they rested in a sitting position for 3 hours. The subjects were maintained in the sitting position for 4 additional hours in one session. In a second session, they exercised for 60 min at 50 % of their VO(2) max and then returned to the sitting position for 3 hours. Respiratory exchange ratio (RER) values were calculated by indirect calorimetry. During the resting session, plasma non-esterified fatty acids (NEFA) and glycerol concentrations rose progressively, whereas RER progressively decreased. During the exercise, plasma catecholamines, NEFA, glycerol, growth hormone and cortisol levels and RER increased while insulin decreased. During the recovery, plasma NEFA increased and glycerol decreased. During the first hour of recovery, RER values were lower and fatty acid utilization higher than during the same period of the resting session. The study shows that exercise induces modifications in hormonal factors promoting lipid mobilization and suggests that exercise provide substantial amounts of NEFA for muscle oxidation during recovery from an exercise bout in obese subjects.     

Human bronchial artery blood flow after lung Tx with direct bronchial artery revascularization.

The inaccuracy of measuring human bronchial artery blood flow has previously been considerable. En bloc double-lung transplantation with bronchial artery revascularization (BAR) using a single conduit offers the unique opportunity of direct measurement of the total bronchial artery blood flow. In eight en bloc double-lung-transplanted patients with complete BAR, the basal blood flow was measured by using a 0.014-in. Doppler guide wire and arteriography. The average peak velocity in the conduit was 12-73 cm/s [+/-2.1 (SD) cm/s], and the conduit diameter was 1.7-3.1 mm [+/-0.10 (SD) mm], giving individual basal flow values between 19 and 67 ml/min [+/-5 (SD) ml/min], or 0.2-1.9% of estimated cardiac output. In three patients basal measurements were followed by injection of nitroglycerin and verapamil into the conduit. This increased the bronchial artery flow to 121-262% of basal values (31-89 ml/min). The measured values appear more physiologically plausible than previous bronchial artery blood flow measurements in humans.     

Effect of plasma lipid levels and obesity on tissue stores of alpha-tocopherol.

Experiments were designed to determine how varying levels of plasma lipids affect tissue deposition of alpha-tocopherol (vitamin E). Hypolipemia was induced by feeding orotic acid, and hyperlipemia was obtained using genetically obese rats. With equal dietary intakes of alpha-tocopherol, hypolipemic rats had lower plasma and tissue concentrations than rats with normal plasma lipids. An exception was liver, which due to fatty enlargement from orotic acid had more alpha-tocopherol. Hyperlipemic obese rats had plasma total lipids and alpha-tocopherol three times those of normal rats with the same intake of alpha-tocopherol. Tissue concentrations of the vitamin, however, were considerably lower in obese rats. Due to their large adipose mass, obese rats had considerably more total body alpha-tocopherol than normal rats. It was concluded that both plasma lipid levels and degree of adiposity are important factors in determining tissue deposition of alpha-tocopherol.     

The control of cholesterol metabolism and plasma lipid levels in infant rats.

Infant rats received an i.p. injection of insulin, anti-insulin serum, streptozotocin, antiglucagon serum or dexamethasone. All substances except the antiinsulin serum, raised the plasma triglyceride level. Both antisera decreased plasma cholesterol levels, while streptozotocin, insulin and dexamethasone caused an increase. The activity of 3-hydroxy-3-glutaryl CoA reductase in liver and brown adipose tissue changed inversely to the cholesterol level. However, small intestinal enzyme activity was increased by insulin administration inspite of the rise in plasma cholesterol.     

A rapid increase in lipoprotein (a) levels after ethanol withdrawal in alcoholic men.

Plasma concentrations of lipoprotein (a) (Lp(a)) were studied in 11 male alcoholics at the end of a drinking period and monitored during subsequent abstinence. Lp(a) levels showed a daily increase for four consecutive days after the beginning of abstinence, the values for the third and the fourth day being significantly higher than those of the first day (p less than 0.05 and p less than 0.01, respectively). The changes in Lp(a) showed no association with the changes in low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol levels. In one alcoholic subject with a heterozygous form of familial hypercholesterolemia who was monitored for 11 days, the Lp(a) levels rose up to the fourth day and remained at a high level thereafter. These results suggest that ethanol ingestion may be associated with a lowering of Lp(a) levels, which may contribute to the delayed progression of atherosclerosis observed in alcohol drinkers. Ethanol intake may be added to the short list of factors that affect the quite stable, genetically determined Lp(a) concentrations in the plasma.     

Time-course changes of plasma lipid levels and lipoprotein pattern after feeding in cultured sea bass, Dicentrarchus labrax L.

Results of a study of plasma lipids levels and lipoprotein pattern modification during digestion in sea bass indicate that, after feeding, non-esterified fatty acids are rapidly delivered in plasma, while triglycerides reach a maximum concentration only 24 h later. The time-course change of the lipoprotein pattern shows a relationship between their concentration and the lipid class carried.     

Effects of a 50 Hz electric field on plasma lipid peroxide level and antioxidant activity in rats

The effects of exposure to extremely low frequency electric fields (ELF EFs) on plasma lipid peroxide levels and antioxidant activity (AOA) in Sprague-Dawley rats were studied. The test was based on comparisons among rats treated with a combination of the oxidizing agent, 2,2'-azobis(2-aminopropane) dihydrochloride (AAPH) and 50 Hz EF of 17.5 kV/m intensity for 15 min per day for 7 days, AAPH alone, EF alone or no treatment. EF significantly decreased the plasma peroxide level in rats treated with AAPH, similar to treatment by ascorbic acid or the superoxide dismutase. Ascorbic acid increased AOA; however, EF and superoxide dismutase did not change AOA compared with sham exposure in stressed rats. No influence on the lipid peroxide level and AOA in unstressed rats was observed with EF exposure alone. Although the administration of AAPH decreased AOA, this decrease did not change when EF was added. These data indicate that the ELF EF used in this study influenced the lipid peroxide level in an oxidatively stressed rat.     

European hamsters (Cricetus cricetus) show a transient phase of insensitivity to long photoperiods after gonadal regression

Annual rhythms of body weight and reproduction in the European hamster (Cricetus cricetus) are the result of an interaction between seasonal changes in day length (photoperiod) and seasonal changes in the responsiveness of animals to these photoperiods. The present study demonstrates that under natural conditions European hamsters are not able to perceive long photoperiods (i.e., a 16L:8D cycle) before mid-November. This is an important difference to other hamster species, in which regrowth of the gonads can be stimulated by exposure to long photoperiods at any stage of gonadal regression. The experiments also demonstrate the existence of an annual phase of sensitivity to long photoperiods that starts around mid-November and extends until March/April. During this phase of sensitivity, exposure to a long photoperiod (16L:8D) induced gonadal regrowth within 3 wk. Additional experiments with an accelerated photoperiodic lighting regimen indicated that a photoperiod of approximately 13 h is necessary to stimulate gonadal regrowth. Under natural light conditions in Stuttgart (48.46 degrees N), a photoperiod of 13 h is reached by the beginning of April, which fits well with the finding that the majority of animals kept under a natural light:dark cycle had well-developed gonads by the end of April. Nevertheless, these animals showed a rather variable timing of gonadal regrowth, ranging from early January to late April. This is most likely the result of two processes: first, an endogenous mechanism (photorefractoriness) that induces gonadal recrudescence without any photoperiodic information while the animals are still in their hibernation burrows, and second, a direct stimulatory effect of long photoperiods.     

Lipid peroxidation causes an increase of lipid order and a decrease of 5'-nucleotidase activity in the liver plasma membrane.

The effect of peroxidation on 5'-nucleotidase activity as well as on membrane microviscosity has been investigated in liver plasma membranes from Wistar rats. The peroxidation was performed with 100 microM H2O2 and 200 microM FeSO4 and/or with 5 mM t-butylhydroperoxide. Treatment of the membranes with these oxidizing agents resulted in an elevation of the transition temperatures of the polarization of the lipid fluorescent probes 1,6 diphenyl-1,3,5 hexatriene (DPH), 3-p-(6-phenyl) 1,3,5 hexatriene phenylpropionic acid (PA-DPH) as well as of the fluorescent thiol reagent N-(1-pyrene) maleimide (1-PM). The peroxidation resulted in a decrease of the activity of 5'nucleotidase. Our data support that the increase of membrane microviscosity of the lipid domain regulates the activity of 5'-nucleotidase.     

Transient increase of plasma ghrelin after laparoscopic adjustable gastric banding in morbid obesity.

Ghrelin is a peptide hormone with orexigenic properties that is produced by the stomach. Ghrelin and leptin are thought to be the main regulators of appetite and body weight. The present study was aimed at evaluating the effect of weight reduction after laparoscopic adjustable gastric banding (LAGB) on metabolic parameters and energy balance regulatory peptides. Patients were evaluated before and 6, 12, 24 or 36 months after the procedure, and a blood sample was obtained. Ghrelin rose 6 and 12 months after LABG, and then returned to near-baseline levels. In our study, the correlation between ghrelin and BMI was weak, but a strong significant correlation was maintained between leptin and BMI. We conclude that ghrelin is mainly stimulated by the negative caloric balance, and hypothesize that ghrelin is involved in maintaining a stable body weight, while leptin signals the body energy store; both hormones together are part of a more complex feedback mechanism.     

Rapid increase in plasma growth hormone after low-intensity resistance exercise with vascular occlusion.

Hormonal and inflammatory responses to low-intensity resistance exercise with vascular occlusion were studied. Subjects (n = 6) performed bilateral leg extension exercise in the seated position, with the proximal end of their thigh compressed at 214 +/- 7.7 (SE) mmHg throughout the session of exercise by means of a pressure tourniquet. Mean intensity and quantity of the exercise were 20% of 1 repetition maximum and 14 repetitions x 5 sets, respectively. In each set, the subjects repeated the movement until exhaustion. Plasma concentrations of growth hormone (GH), norepinephrine (NE), lacate (La), lipid peroxide (LP), interleukin-6 (IL-6), and activity of creatine phosphokinase (CPK) were measured before and after the exercise was finished and the tourniquet was released. Concentrations of GH, NE, and La consistently showed marked, transient increases after the exercise with occlusion, whereas they did not change a great deal after the exercise without occlusion (control) done at the same intensity and quantity. Notably, concentration of GH reached a level approximately 290 times as high as that of the resting level 15 min after the exercise. IL-6 concentration showed a much more gradual increase and was maintained at a slightly higher level than in the control even 24 h after exercise. Concentrations of LP and CPK showed no significant change. The results suggest that extremely light resistance exercise combined with occlusion greatly stimulates the secretion of GH through regional accumulation of metabolites without considerable tissue damage.     

A role for the transient increase of cytoplasmic free calcium in cell rescue after photodynamic treatment.

Chinese hamster ovary (CHO) cells and T24 human bladder transitional carcinoma cells were treated with the photosensitizers aluminum phthalocyanine (AlPc) and hematoporphyrin derivative (HPD), respectively. Exposure of both sensitized cell lines to red light caused an immediate increase of cytoplasmic free calcium, [Ca2+]i, reaching a peak within 5-15 min after exposure and then returning to basal level (approximately 200 nM). The level of the peak [Ca2+]i depended on the light fluence, reaching a maximum of 800-1000 nM at light doses that kill about 90% of the cells. Loading the cells with the intracellular calcium chelators quin2 or BAPTA prior to light exposure enhanced cell killing. This indicates that increased [Ca2+]i after photodynamic therapy (PDT) contributed to survivability of the treated cells by triggering a cellular rescue response. The results of experiments with calcium-free buffer and calcium chelators indicate that both in CHO cells treated with AlPc and with HPD-PDT of T24 cells extracellular Ca2+ influx is mainly responsible for elevated [Ca2+]i. PDT is unique in triggering a cell rescue process via elevated [Ca2+]i. Other cytotoxic agents, e.g., H2O2, produce sustained increase of [Ca2+]i that is involved in the pathological processes leading to cell death.