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Proton MR spectroscopy and MR imaging in acute and chronic multiple sclerosis--ringlike appearances in acute plaques.

PURPOSE: We wanted to compare the metabolite status of brain lesions in different clinical subtypes of multiple sclerosis (MS). Two acute MS lesions with ringlike appearances were also investigated. MATERIAL AND METHODS: Twenty-three clinically stable MS patients, 2 patients with acute relapses, and 15 healthy individuals were examined by MR imaging and localized proton MRS. RESULTS: No metabolite differences were seen in plaques of different subtypes. Decreased NAA/Cr and NAA/choline ratios as well as increased inositol/Cr ratios were observed in the plaques of the clinically stable or chronic active MS patients as compared with controls. The ring plaques had hyperintense cores with surrounding halos, separated from the cores by rings with low signal intensity in T2-weighted images. The core exhibited a prolonged T2 relaxation time. Proton spectra initially contained lactate. CONCLUSION: No differences between the metabolite status of nonacute plaques in different clinical subtypes could be detected. The ring plaques contained lactate signals indicating oedema, inflammation, and macrophage invasion, and may be transition forms between acute oedematous lesions and chronic demyelinated plaques.

Adult↗

Water intake and excretion, urinary solute excretion and some stress indicators in mink (Mustela vison): effect of ambient temperature and quantitative water supply to lactating females.

Lactation is a physiologically demanding period in mink production, during which kit and dam losses may occur. Ambient temperature and quantitative water supply are thought to affect animal performance and well-being, but conclusive data in the literature are sparse. Therefore, effects of ambient temperature (Ta; low, about 5 degrees; medium, about 15 degrees; high, average 20-25 degrees) and water supply (ad libitum (N), or 10% extra supplementation in the food (E)) were investigated regarding effects on quantitative water intake and excretion, urine osmolality and solute excretion, and urinary cortisol and catecholamines as stress indicators in an experiment with twelve lactating mink with litters of three to seven kits in three consecutive periods, lasting 3, 3 and 2 d respectively. Kit ages ranged from 15 to 20 d at the end of the experiment. Water requirement for milk production (factorial calculations) and water available for evaporation (balance component) were estimated. Period, and hence mainly Ta, had a significant influence on intake of metabolizable energy, quantitative water intake and excretion, but there was less effect of water supply. The total water intake and excretion were very high in relation to the weight of the animals as an effect of lactation. Water intake and excretion, and urinary Na excretion, seemed to be less accurately regulated compared with corresponding functions in non-lactating animals. Rectal temperature increased with increasing Ta, possibly as a means of decreasing evaporative water loss. Water output in milk was estimated to increase from 118 g/d at low Ta to 134 g/d at high Ta. The amounts of water available for evaporation were estimated to be 42, 58 and 69 g/kg0.75 at low, medium and high Ta. Cortisol data did not indicate that the animals experienced negative stress. It was concluded that prolonged periods of high Ta may be hazardous for lactating mink because of decreased intake of metabolizable energy resulting in energy deficit and excessive mobilization of body reserves simultaneously as the requirement for intake of water increases considerably.

Analysis of Variance↗

Reproductive experience and opioid regulation of luteinizing hormone release in female rats.

The objective of the present study was to determine whether reproductive experience that produces shifts in opioid regulation of prolactin secretion and behavioural functions also alters opioid regulation of LH during the oestrous cycle or lactation. In Expt 1 the effect of naloxone administration (i.v.) on LH was compared between age-matched, nulliparous and primiparous, catheterized female rats on dioestrus II. In Expt 2, the effects of multiple reproductive experiences on opiate control of LH were investigated using cyclic, nulliparous and multiparous (three litters) rats. In both experiments, no differences in naloxone-stimulated LH release were found between groups even though multiple reproductive experiences resulted in the prolongation of oestrous cyclicity. In Expt 3, day 8 lactating primiparous rats were administered 2, 5, 10 or 25 mg naloxone kg-1 i.v. The three lowest naloxone doses, but not the 25 mg kg-1 dose, significantly increased LH concentrations. The possible effects of prior reproductive experience on opioid control of LH during lactation were then investigated. Naloxone at 0.5 mg kg-1, but not at 2 mg kg-1 or 10 mg kg-1, stimulated a significantly greater rise in LH in multiparous (two litters) than in primiparous females. Overall, these data indicate that while modest differences were found in naloxone-induced LH responses between multiparous and primiparous animals during lactation, reproductive experience did not significantly alter opioid regulation of LH during subsequent oestrous cycles at the naloxone doses examined. Hence, the effects of reproductive experience on opioid regulation of LH are less pronounced than those previously found for opioid regulation of prolactin and behaviour.

Analysis of Variance↗

Factors influencing fertility of Holstein dairy cows: a multivariate description.

Eighty-two multiparous cows of high and low genetic merit were fed one of two isonitrogenous (19.3% crude protein), isoenergetic (11.3 MJ of metabolizable energy) diets that differed in ratio of rumen-undegradable protein to rumen-degradable protein. Factors that influenced reproductive performance were investigated using logistic regression and survival analysis. Significant associations were identified between reproductive performance and indicators associated with nutrient balance. Cows with higher dry matter intake were more likely to show signs of estrus at first ovulation and to become pregnant by d 150 of lactation. Increased ratio of plasma glucose to 3-hydroxybutyrate was associated with a greater probability of estrous expression at first ovulation. Concentrations of plasma cholesterol were positively associated with expression of estrus at first ovulation, interval from calving to conception, and likelihood of conception and pregnancy. Greater concentrations of nonesterified fatty acids in plasma were associated with a lower probability of conception by d 150 of lactation. Increased yield of fat-corrected milk during early lactation was negatively associated with expression of estrus at first ovulation and probability of pregnancy by d 150 of lactation. Cows of high genetic merit were less likely to show signs of estrus at first ovulation. Cows fed the high rumen-degradable-protein diet that also lost more body weight during early lactation were less likely to conceive at first service and to have a prolonged interval from calving to conception. Continued selection for increased production of milk and a more negative nutrient balance during early lactation may reduce reproductive performance particularly for cows fed high concentrations of rumen-degradable protein.

3-Hydroxybutyric Acid↗

Safety and efficacy of ginkgo (Ginkgo biloba) during pregnancy and lactation.

BACKGROUND: There is a lack of basic knowledge on the part of both clinicians and patients as to the indications for use and safety of herbal medicines used in pregnancy and lactation. This is one article in a series that systematically reviews the evidence for commonly used herbs during pregnancy and lactation. OBJECTIVES: To systematically review the literature for evidence on the use, safety, and pharmacology of ginkgo focusing on issues pertaining to pregnancy and lactation. METHODS: We searched 7 electronic databases and compiled data according to the grade of evidence found. RESULTS: There is some very weak scientific evidence from animal and in vitro studies that ginkgo leaf has antiplatelet activity, which may be of concern during labour as ginkgo use could prolong bleeding time. Low-level evidence based on expert opinion shows that ginkgo leaf may be an emmenagogue and have hormonal properties. The safety of ginkgo leaf during lactation is unknown. Patients and clinicians should be aware of past reports of ginkgo products being adulterated with colchicine. CONCLUSIONS: Ginkgo should be used with caution during pregnancy, particularly around labour where its anti-platelet properties could prolong bleeding time. During lactation the safety of ginkgo leaf is unknown and should be avoided until high quality human studies are conducted to prove its safety.

Animals↗

Colonic lactate metabolism and D-lactic acidosis.

D-Lactic acidosis is seen in patients with intestinal bypass or short bowels in whom colonic produced D-lactate accumulates. An intestinal bypassed patient with D-lactic acidosis had higher fecal D-lactate (122.4 mmol/liter) and L-lactate (90.1 mmol/liter) than described before in humans. D-Lactate fluctuated between 0.5 and 3.1 mmol/liter in plasma (normal < 0.1 mmol/liter) and between 1.1 and 52.8 mmol/liter in urine (normal < 0.7 mmol/liter) within a few hours, indicating that the human organism do metabolize and excrete D-lactate. The patient with D-lactic acidosis had a 10-fold increased DL-lactate production from glucose in fecal homogenates compared to 14 healthy controls and a patient with intestinal bypass, who did not have D-lactic acidosis. A 67% carbohydrate (starch)-enriched diet resulted in a minor elevation of fecal and plasma lactate, whereas 50 + 100 + 150 g of ingested lactose increased D-lactate in feces (84.0 mmol/liter) and plasma (2.3 mmol/liter) considerably in the patient with D-lactic acidosis. Intestinal prolongation (22 cm ileum) had a temporary effect on fecal and plasma D-lactate, but intestinal continuity was reestablished 26 months later because D-lactic acidosis recurred (plasma 8.6 mmol/liter, urine 101.3 mmol/liter). Large amounts of lactulose (160 g/day) to 12 normal individuals increased D-lactate to 13.6 +/- 3.5 mmol/liter in feces, but never increased D-lactate in plasma or urine. The in vitro fermentation of glucose in fecal homogenates increased DL-lactate, which disappeared after complete metabolization of the glucose. L-Lactate was converted to D-lactate and vice versa, and both were degraded to the short-chain fatty acids acetate, propionate, and butyrate. An infrequent, but elevated ability of the colonic flora to produce lactate may be a prerequisite for D-lactic acidosis to occur and may explain why the syndrome is so seldom seen even in patients with intestinal bypass or short bowels. The suggestion that D-lactate is not metabolized and hence accumulates is probably not valid.

Acidosis, Lactic↗

Effects of hyperglycemia on gasping and autoresuscitation in newborn rats.

The aim of this study was to test the effects of glucose on the gasping ability and survival in a rat pup model during acute anoxia. Newborn rat pups of both 1 and 8 days of age were given glucose (30 and 60 mg/animal) or saline intraperitoneally and subsequently subjected to anoxia (100% N2). Glucose supplement induced hyperglycemia. Respiration was recorded by barometric plethysmography. The rat pups responded to acute anoxia with a robust sequence of respiratory pattern: hyperpnea, primary apnea, hypoxic gasping and secondary apnea. During anoxia the 1-day-old rats gasped much longer than the 8-day-old rats (23.4 +/- 1.0 vs. 6.1 +/- 0.5 min, p < 0.001). No difference was found in gasping duration between the saline control and the glucose-supplemented 1-day-old rat pups. The 8-day-old supplemented rats gasped much longer (9.3 +/- 0.5 min) than the control rats (6.1 +/- 0.5 min, p < 0.01). The animals autoresuscitated when they received oxygen (100%) during the gasping period. When oxygen was given after the gasping period, the survival rate was 33.3% in control and 0% in supplemented 1-day-old rats, and 100% in control and 50% in glucose-supplemented 8-day-old rats (p < 0.02). Further controlled experiments for a fixed period of anoxia to 13.5 min resulted in survival rates of 50.0% for controls and 28.6% for supplemented animals, respectively. The overall survival rate was then 85.2% in control and 52.9% in supplemented 8-day-old rats (p < 0.05). Lactate concentration in blood rapidly increased in the first 6 min of anoxia and thereafter gradually increased to 22.1 mmol/l around the last gasp in the 1-day-old rats. Hyperglycemia did not cause further accumulation of lactate despite a transient elevation over the control rats at 6 min of anoxia. In the 8-day-old supplemented animals the lactate level was only modestly increased, probably due to the prolonged gasping period. In conclusion, we found that gasping performance was well preserved in the 8-day-old glucose-supplemented rats, whereas the autoresuscitation mechanism after the last gasp might be altered due to hyperglycemia. In addition, the accumulation of lactate in the blood did not affect the gasping performance and the mechanisms of autoresuscitation.

Animals↗

Prolonged adenine nucleotide resynthesis and reperfusion injury in postischemic skeletal muscle.

Skeletal muscle ischemia results in energy depletion and intracellular acidosis. Reperfusion is associated with impaired adenine nucleotide resynthesis, edema formation, and myocyte necrosis. The purpose of these studies was to define the time course of cellular injury and adenine nucleotide depletion and resynthesis in postischemic skeletal muscle during prolonged reperfusion in vivo. The isolated canine gracilis muscle model was used. After 5 h of ischemia, muscles were reperfused for either 1 or 48 h. Lactate and creatine phosphokinase (CPK) release during reperfusion was calculated from arteriovenous differences and blood flow. Adenine nucleotides, nucleosides, bases, and creatine phosphate were quantified by high-performance liquid chromatography, and muscle necrosis was assessed by nitroblue tetrazolium staining. Reperfusion resulted in a rapid release of lactate, which paralleled the increase in blood flow, and a delayed but prolonged release of CPK. Edema formation and muscle necrosis increased between 1 and 48 h of reperfusion (P less than 0.05). Recovery of energy stores during reperfusion was related to the extent of postischemic necrosis, which correlated with the extent of nucleotide dephosphorylation during ischemia (r = 0.88, P less than 0.001). These results suggest that both adenine nucleotide resynthesis and myocyte necrosis, which are protracted processes in reperfusing skeletal muscle, are related to the extent of nucleotide dephosphorylation during ischemia.

Adenine Nucleotides↗

Physiological adjustments of facial cooling during exercise.

Physiological and metabolic output responses to facial cooling during a graded maximal exercise and a prolonged submaximal exercise lasting 30 min at 65% VO2 max were investigated in five male subjects. Pedalling on a cycle ergometer was performed both with and without facial cooling (10 degrees C, 4.6 M.S-1). Facial cooling at the end of greated maximal exercise apparently had no effect on plasma lactate (LA), maximal oxygen consumption (VO2 max), maximal heart rate (HR max), rectal temperature (Tre), work load, lactate threshold (LT), ventilatory threshold (VT) and onset of blood lactate accumulation (OBLA). However, the response to facial cooling after prolonged submaximal exercise is significantly different for heart rate and work load. The results suggest that facial wind stimulation during maximal exercise does not produce a stress high enough to alter the metabolic and physiological responses.

Adaptation, Physiological↗

Lactate threshold does not influence metabolic responses during exercise in cyclists.

The purpose of this study was to compare plasma markers of metabolic stress and other physiological parameters during prolonged endurance exercise of different intensity in trained subjects possessing a "high" or "low" lactate threshold (LT) expressed as a percentage (%) of peak power output (PPO). Fifteen trained male cyclists completed an incremental exercise test for determination of PPO and the LT (% PPO). Each subject then completed a 90-min and 20-min exercise trial at an intensity representing 75 and 85 % of PPO, respectively. Blood lactate (La), as well as plasma hypoxanthine (Hx) and uric acid (UA) were measured during each exercise trial. The responses in two groups, one (n = 8) with a LT approximately 65 % PPO (LT (low)), the other group (n = 7) with a LT approximately 75 % (LT (high)) (p < 0.01), were then compared. With the exception of UA, La and Hx increased significantly (p < 0.01) throughout each exercise trial compared to rest. However, there were no significant differences in each trial between the two groups of cyclists. There were also no significant differences in the other physiological parameters in each exercise trial between the subjects in LT (low) and LT (high). This study demonstrates that in trained cyclists homogeneous in terms of PPO, plasma markers of metabolic demand during prolonged exercise are not influenced by the LT when measured in an incremental exercise test.

Adult↗

Acetone metabolism in mice: increased activity in mice heterozygous for obesity genes.

Mice were found to convert acetone to lactate at appreciable rates. The conversion of acetone to gluconeogenic precursors could provide additional glycolytic intermediates that would allow the more complete utilization of lipid stores and increase survival time during starvation. In mice that were starved for 3 days or were provided with acetone in the drinking water the acetone-metabolizing pathway was induced to levels severalfold normal. Mice heterozygous for obesity-producing mutations, either obese (ob/+) or diabetes (db/+), showed induction of the activity of this pathway to a significantly higher degree than did homozygous normal (+/+) mice of the same strain. This more effective conversion of acetone to lactate exhibited by heterozygous mice could account for their prolonged survival on a starvation regimen compared to that of normal homozygotes. The rate-limiting step in the pathway appears to be the conversion of acetone to a hydroxylated derivative. The enzyme system effecting this conversion is an NADPH-requiring microsomal oxygenase found in the liver.

Acetone↗

Mechanism for glycogenolysis in nonexercising human muscle during and after exercise.

Arterial-deep venous differences for glucose and lactate across the nonexercising forearm were determined in healthy subjects during 3 h of leg exercise at 50% of maximum oxygen uptake and during 20-min recovery. At 160 min of exercise 0.5 mg propranolol was infused into the brachial artery. The results were compared with a control group that did not receive propranolol during exercise. Exercise stimulated to increased forearm lactate release which was higher than that which could be accounted for by the simultaneous blood glucose uptake. After propranolol forearm lactate production decreased during and after exercise while the controls still showed increasing lactate release. In contrast to the control values the lactate production by the blocked forearm could be accounted for by the glucose uptake. It is concluded that the stimulating effect of prolonged exercise on nonexercising muscle that persists during recovery is characterized by increased lactate release derived from beta-adrenergically stimulated glycogenolysis.

Adult↗

Effects of environmental and other stressors on blood hormone patterns in lactating animals.

Recent data on various environmental stressors and blood hormone patterns are presented for lactating cattle. Known stressor effects of such factors as environmental temperature, air pollution, and noise on the plasma thyroxine, growth hormone, cortisol, prolactin, progesterone, luteinzing hormone, epinephrine, and norepinephrine of lactating cattle are discussed. Information on stressor effects is lacking on glucagon, insulin, vasopressin, calcitonin, oxytocin, thyrotrophic hormone, follicle stimulating hormone, melatonin, parathyroid hormone, and estrogens in the lactating cow. The importance of evaluating both the effect of environmental stressor and of production or lactation intensity is emphasized in the overall interpretation of changes in hormone of plasma. The short and long term environmental heat effects on thyroxine, cortisol, and growth hormone are clear with initial increased due to acute stressors and a decline of amounts in plasma after prolonged exposure to stressors. The relationship of amounts in plasma of these hormones to milk production appears to be related directly for cortisol, growth hormone, and prolactin with an inverse relationship with thyroxine. Epinephrine and norepinephrine seem to be elevated with prolonged environmental heat stress. However, the influence of intensity of lactation has not been measured. Hormones in plasma as they relate to stressor effects and milk production are important as potential indicators of the physiological state of a cow and reflect the physiological compensations a cow undergoes at various lactation intensities and/or stress exposure.

Adrenal Cortex Hormones↗

Enzymes and factors controlling vitamin D metabolism and action in normal and milk fever cows.

In milk fever (parturient paresis), calcium homeostatic mechanisms, regulated by parathyroid hormone and 1,25-dihydroxyvitamin D, fail to maintain normal blood calcium concentrations, resulting in severe hypocalcemia. The precise nature of the endocrine defect is unknown. Secretion of parathyroid hormone and production of 1,25-dihydroxyvitamin D is similar in most cows with milk fever or without. However, there are some cows that fail to produce adequate 1,25-dihydroxyvitamin D at the onset of lactation. These tend to be cows that will suffer prolonged hypocalcemia and relapse after treatment. Assuming that most cows produce adequate amounts of both hormones, the next logical cause of milk fever might be a failure of tissues to respond to calcium-regulating hormones. Older cows are more likely to develop milk fever than younger ones. We have found that tissue 1,25-dihydroxyvitamin D receptor concentrations decline with age, leaving the tissues less able to respond to 1,25-dihydroxyvitamin D. We also have found that tissue 1,25-dihydroxyvitamin D receptor concentrations increase during pregnancy and lactation in the cow. Intestinal 1,25-dihydroxyvitamin D receptor concentration does not appear to be different in cows with or without milk fever in cows of similar ages. However, intestinal 1,25-dihydroxyvitamin D receptor numbers decrease precipitously at parturition, which may in part be responsible for the development of hypocalcemia in dairy cattle.

Absorption↗

Effects of selective cooling of the facial area on physiological and metabolic output during graded maximal or prolonged submaximal exercise.

Physiological and metabolic output responses to facial cooling during a graded maximal exercise and a prolonged submaximal exercise lasting 30 min at 65% VO2 max were investigated in five male subjects. Pedalling on a cycle ergometer was performed both with and without facial cooling (10 degrees C, 4.6 m s-1). Facial cooling at the end of graded maximal exercise apparently had no effect on plasma lactate (LA), maximal oxygen consumption (VO2 max), maximal heart rate (HR max), rectal temperature (Tre), work-load, lactate threshold (LT), ventilatory threshold (VT) and onset of blood lactate accumulation (OBLA). However, the response to facial cooling after prolonged submaximal exercise is significantly different for heart rate and work-load. The results suggest that facial wind stimulation during maximal exercise does not produce a stress high enough to alter the metabolic and physiological responses.

Adult↗