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PubMed1991

Responses by lactating cows in commercial dairy herds to recombinant bovine somatotropin.

Cows (890) in 15 US herds were assigned randomly in equal numbers to control or bST injections (500 mg in a prolonged-release form every 14 d for 12 wk) within three stages of lactation (57 to 100, 101 to 140, and 141 to 189 d postpartum) and two parity groups (primiparous and multiparous). Yield and milk composition were monitored 1 d/wk for 16 wk including 2 wk pretreatment and 2 wk posttreatment. Increases in milk and FCM due to bST injections were less at 57 to 100 d than at 101 to 189 d postpartum (milk 3.6 vs. 5.5; FCM 3.9 vs. 6.1 kg/d per cow), and increases in milk and FCM were more for multiparous than for primiparous cows (milk 5.5 vs. 4.2; FCM 6.0 vs. 4.7 kg/d cow). Temporarily, concentration of milk fat increased and protein decreased; later, concentrations for control and injected cows were similar. Postinjection milk fat concentration decreased, but milk protein concentration increased temporarily. The net increase in milk (and FCM) varied significantly among herds from 2.9 to 7.6 kg/d per cow (mean, 4.9 kg). Responses in FCM were similar over a wide range of pretreatment yields. A great variety of feed ingredients were fed as total mixed rations, and nutrient concentrations varied greatly. The SCC were similar before, during, and after treatment, but increase in FCM of injected cows exhibited a negative correlation with pretreatment SCC. Changes in body condition score of sometribove-injected cows varied among herds (.25 to -.45) and averaged -.02 compared with .07 for controls. There was no pattern in incidence of mastitis during sometribove injections.

Animal Feed↗

PubMed1988

Blood glutathione oxidation during human exercise.

To examine the effects of increased O2 utilization on the glutathione antioxidant system in blood, eight moderately trained male volunteers were exercised to peak O2 consumption (VO2peak) and for 90 min at 65% of VO2peak on a cycle ergometer. Blood samples were taken during exercise, and for up to 4 days of recovery from submaximal exercise. During exercise to VO2peak, blood reduced glutathione (GSH) and total glutathione [GSH + oxidized glutathione (GSSG)] did not change significantly. Lactate (L), pyruvate (P), and L/P increased significantly from rest values (P less than 0.01). During prolonged submaximal exercise, GSH decreased 60% from control, and GSSG increased 100%. Total glutathione, glucose, pyruvate, and lactate concentrations and L/P did not change significantly during sustained exercise. During recovery, GSH and GSH/GSSG increased from exercise levels and significantly overshot preexercise levels, reaching maximum values after 3 days. Oxidation of GSH during submaximal exercise and its reduction in recovery suggest increased formation of active O2-. species in blood during physical exercise in moderately trained males.

Adult↗

PubMed1976

Low apparent creatine kinase activity and prolonged lag phases in serum of patients with metastatic disease: elimination by treatment of sera with sulfhydryl agents.

We find lag phases exceeding 20 min in measuring creatine kinase activity, by using the kinetic creatin phosphate leads to creatine assay, in sera of some patients with carcinoma metastatic to the liver. Such long lag phases are accompanied by a decreased apparent enzyme activity. These problems are eliminated by adding sulfhydryl agents to the serum before assay, but not by adding more of such agents to the assay reagent. beta-Mercaptoethanol is supperior to Cleland's reagents, glutathione, and cysteine. The long lag phases could not be explained by inadequate activity of the coupling enzymes, interference with the coupling steps, high proportions of cardiacisoenzymes activity, simple oxidation of the enzyme, low concentrations of albumin, or increased concentrations of glutathione reductase, lactate dehydrogenase, or uric acid. We conclude that the prolonged lag phases reflect inadequate reactivation of the enzyme by sulfhydryl agents under the usual assay conditions. Reactivation before assay can prevent potentially serious negative errors in the assay of creatine kinase.

Adenosine Triphosphate↗

PubMed1976

Myocardial protection during bypass and arrest. A possible hazard with lactate-containing infusates.

Severe myocardial tissue damage may results from the use of prolonged ischemic arrest during cardiac surgery. A number of experimental and clinical studies have been reported in which various protective agents have been infused into the coronary vessels before the onset of ischemia in an attempt to reduce or delay this damage. Although these agents are undoubtedly able to protect the ischemic myocardium, their efficacy may be considerably reduced or enhanced by the composition of the medium in which these agents are dissolved. In experiments with a rat heart model of bypass and ischemic arrest, we found that lactate-based media are detrimental to optimal tissue protection.

Animals↗

PubMed1991

Augmentation of endotoxic lethality and glucose dyshomeostasis by phorbol ester.

To investigate the role of protein kinase C (PKC) activation in the pathogenesis of endotoxin (ETX) shock, the in vivo effects of phorbol 12-myristate 13-acetate (PMA) on ETX-induced lethality and glucose dyshomeostasis were determined. Fed rats (300-400 g) were treated intravenously with incremental doses of Salmonella enteritidis ETX and either the vehicle, 110 mg/kg ip dimethyl sulfoxide (DMSO), or 0.5 mg/kg ip PMA dissolved in DMSO. PMA significantly increased ETX-induced lethality to doses of 1.0-20 mg/kg. PMA augmented the initial hyperglycemia, late hypoglycemia, and hyperlactacidemia after 1 mg/kg iv ETX to rats anesthetized with pentobarbital sodium. In contrast, 4 alpha-phorbol, a phorbol derivative that does not activate PKC, had no effect on either lethality or the glucose and lactate responses. Hyperinsulinemia after 1 mg/kg iv ETX was prolonged by PMA but not by 4 alpha-phorbol. Insulin tolerance testing (0.5 U/kg iv) produced an exaggerated hypoglycemic response in PMA-treated endotoxic (0.33 mg/kg) rats. Glucose tolerance to 1.2 g/kg iv was increased by ETX and PMA attenuated the increased tolerance. Thus PKC activation may be involved in the pathogenesis of lethal endotoxicosis and associated glucose dyshomeostasis.

Animals↗

PubMed1985

Intestinal glucose metabolism during development. II. The role of glucocorticoids and weaning.

Prolonged suckling, until 25 postnatal days, delays the increase in jejunal oxidation of glucose both to lactate and to CO2 that occurs after artificial weaning at 20 days of age. The cortisone-mediated increase in intestinal sucrase activity which normally occurs by 20 days is not effected by prolonged suckling. Following precocious weaning at 16 days, the rate of jejunal glucose oxidation to lactate and to CO2 increases, over a 48-h period, to adult rates. Exogenous cortisone treatment at 10-13 postnatal days, before the endogenous steroid burst, does not change the rate of glucose oxidation in suckling animals. After weaning, both at 20 days of age and precociously at 16 days, the rate of glucose oxidation to lactate and to CO2 increases within 24 h in those animals who received early steroid treatment, in comparison to 48-72 h in untreated controls. After prolonged suckling until 25 days, there is no effect of early steroid treatment. We conclude that neither endogenous glucocorticoid secretion nor exogenous cortisone treatment alters the rate of glucose oxidation in jejunum of suckling animals despite the induction of jejunal sucrase activity. After early cortisone treatment, glucose oxidation increases within 24 h of normal of precocious weaning.

Age Factors↗

PubMed1976

Carbohydrate metabolism in fetal and neonatal rat brain during anoxia and recovery.

Systemic and cerebral metabolic responses to acute anoxia were studied in term-fetal and neonatal rats in order to account for the greater anoxic tolerance of fetuses. Measurements of blood acid-base balance were correlated with changes in the concentrations of adenine nucleotides, creatine, phosphocreatine, and glycogen in brain, and of glucose, pyruvate, and lactate in brain, blood, and cerebrospinal fluid during 1) exposure (20-40 min) to 100% nitrogen at 37 degrees C, and 2) subsequent recovery in air. Blood PCO2 was higher initially in fetuses and increased more rapidly during anoxia in fetuses than in neonates, exceeding 150 mmHg after 20 min. Brain glycogen, phosphocreatine, and total adenine nucleotides declined more slowly in fetuses than in neonates during anoxia, whereas brain glucose levels declined at similar rates in the two groups. From the changes in these preformed and potential energy stores, it was estimated that total cerebral energy consumption during anoxia was significantly lower in fetuses. The data suggest that the more severe hypercapnia superimposed on anoxia in fetuses decreased cerebral metabolic demands, and thus prolonged survival. An incidental finding was that L-lactate readily enters the immature brain from the blood during anoxia, and in the early recovery phase may constitute the preferred substrate for cerebral oxidative metabolism, sparing glucose.

Adenosine Triphosphate↗

PubMed1984

Suckling and serum prolactin and LH concentrations in lactating rats.

The frequency of pup sucking behaviour was related to serum concentrations of prolactin and LH in rats during various phases of lactation. Sucking frequency and prolactin levels decreased and LH levels increased as lactation progressed. There was no clear relationship between sucking frequency and either prolactin or LH levels. Serum prolactin concentrations were highest when the rats spent most of their time away from their pups and lowest when the rats spent most of their time with the pups attached to their nipples. Prolactin was secreted episodically during prolonged continuous nipple stimulation. Removal of the pups in late lactation and replacement with a newborn litter increased sucking frequency but did not affect serum LH levels and only marginally increased serum prolactin levels. Injection of the dopamine receptor antagonist domperidone produced a far more pronounced release of prolactin from the pituitary gland in early than in late lactation. A circadian control mechanism and an episodic pattern of release may contribute to the great variation in serum prolactin concentrations seen in early lactation; decreased pituitary sensitivity to dopamine receptor blockade may be related to the low concentration of serum prolactin found in late lactation.

Animals↗

PubMed1995

Exogenous lactate interferes with cell-cycle control in Balb/3T3 mouse fibroblasts.

PURPOSE: Previous studies have shown that exogenous lactate may influence proliferation rates, radiation sensitivity, and postirradiation repair capacity of mammalian cells. In the present study, we addressed the question of potential underlying mechanisms and, therefore, examined effects of exogenous lactate on proliferation rates and cell-cycle distribution in immortal but nontumorigenic mammalian cells. METHODS AND MATERIALS: Cells were grown at 37 degrees C in an incubator with 5% CO2 and 95% air, in a culture medium supplemented or not with lactate at a 10 mM concentration. Daily, we changed the culture medium and counted cells per dish. On selected days, cell-cycle distribution was determined by flow cytometry. Balb/3T3 mouse fibroblasts were used. RESULTS: During the exponential phase of cell proliferation, mean population doubling time was significantly increased from 17.7 to 19.9 h, due to selective prolongation of G2/M. However, in density-inhibited cultures, exogenous lactate stimulated entry into S and proliferation to a significantly higher saturation density. CONCLUSIONS: These findings indicate that exogenous lactate interferes with mechanisms of cell-cycle control at two different points in the cell-cycle, depending on cell density and the resulting absence or presence of inhibition of cell proliferation. Interference with cell-cycle control may underly the modification by exogenous lactate of radiosensitivity and postirradiation repair capacity in mammalian cells.

3T3 Cells↗

PubMed2001

Structure and sequence conservation of a putative hypoxia response element in the lactate dehydrogenase-B gene of Fundulus.

Many aquatic habitats are characterized by periodic or sustained episodes of low oxygen concentration, or hypoxia, and organisms that survive in these habitats do so by utilizing a suite of behavioral, physiological and biochemical adjustments to low oxygen (1-3). In the killifish Fundulus heteroclitus, one response to prolonged exposure to hypoxia is an increase in the activity of lactate dehydrogenase-B (LDH-B), the terminal enzyme of anaerobic glycolysis, in liver tissue (4). An increase in glycolytic enzyme activity also occurs in mammalian cells during hypoxia, a process due, in part, to increased rates of gene transcription mediated by the hypoxia-inducible transcription factor, HIF-1 (5). Given that a homolog of HIF-1 has been identified in fish (6), we hypothesized that HIF might be involved in the observed up-regulation of LDH-B in F. heteroclitus. Herein, we describe the presence of DNA elements in intron 2 of the Ldh-B gene from F. heteroclitus that resemble hypoxia response elements (HRE) describedfor mammalian genes (7-10). Specifically, over a region of approximately 50 base pairs we identified two consensus HIF-1 binding sites, as well as DNA elements that may bind other transcription factors (e.g., cyclic AMP response elements; CRE). We found that these sites were perfectly conserved among geographically diverse populations of F. heteroclitus, as well as being highly conserved among multiple species in the genus Fundulus. The spacing, orientation, and sequence conservation of these putative regulatory elements suggest that they may be functionally involved in the hypoxic regulation of Ldh-B in these fish.

Animals↗

PubMed1991

[Lactation behavior and delivery care in a group of women from a Mexican rural community].

This article presents a brief discussion on the role that "medical practice" plays, related to the type of infant lactation after delivery, and breast-feeding practice during the first months of life. Data on hospital routines and how these predispose artificial feeding practices are seen from a critical angle. The information presented in this paper corresponds to a project carried out in a rural community of the state of México, called Malinalco, where the lactation behavior of 65 women after birth of the child, was followed as of their last period of pregnancy. The main objectives of the study were to determine the relationship between the place of delivery (hospital or home delivery) and the type of lactation practiced by the mothers, as well as to determine the infants nutritional status during their first year of life. Results showed that the greater part of women from the sample were young others (less than 30 years old) with one or two children. As to the place where delivery took place, 72% of the sample were attended by midwives at their own homes, and at last 65% practiced breast feeding exclusively during the first three months. No significant correlation between these two indicators (place of delivery and type of lactation) was found, although a tendency to a more prolonged breast-feeding practice was observed in those women who delivered at home. Problems related to weaning practices were detected, since they start this only with bean broth after five months of life. Finally, information on nutritional status during the first 12 months of life, shows serious nutritional problem after the child's third month of life, since the normality percentage starts decreasing while there occurs a significant increase of 1st an 2nd degree malnutrition.

Age Factors↗

PubMed1993

Bromocriptine treatment of periparturient goats: long-term suppression of prolactin and lack of effect on lactation.

British Saanen dairy goats (n = 10) were treated with bromocriptine or vehicle from day 147 of pregnancy to day 4 post partum, a treatment duration of 8.8 +/- 1.7 d (mean +/- SEM). The periparturient prolactin surge was abolished by this treatment, but there were no significant effects on plasma growth hormone or insulin concentrations. Lactogenesis was delayed in the bromocriptine-treated goats, milk yields being significantly depressed (P < 0.01) for the first week of lactation. Yields had recovered to control values by day 10 when prolactin concentrations were still significantly depressed. Mammary gland biopsies were taken on day 4 post partum from five animals in each group. Using this tissue, no significant differences could be shown in mammary morphology or DNA synthesis, but the RNA:DNA ratio was significantly reduced (P < 0.05). After week 1, there were no significant differences between bromocriptine-treated and control goats in milk yield, milk composition, udder volume, time of peak yield or persistence. The goats given short-term bromocriptine treatment at parturition showed prolonged effects on prolactin secretion, their seasonal prolactin rise being severely blunted (P < 0.001). A normal lactation is therefore not prevented in goats by a delay in lactogenesis, suppression of prolactin at parturition or the resulting prolonged depression of circulating prolactin. Goats in established lactation given bromocriptine for 8 d showed, by contrast, a rapid recovery of plasma prolactin concentrations within 5 d post treatment. Milk yield declined significantly (P < 0.03) compared with pretreatment values during and for 1 week after bromocriptine but then began to recover, with no significant change in vehicle-treated goats.

Animals↗

PubMed1974

Hepatic ketogenesis and gluconeogenesis in humans.

Splanchnic arterio-hepatic venous differences for a variety of substrates associated with carbohydrate and lipid metabolism were determined simultaneously with hepatic blood flow in five patients after 3 days of starvation. Despite the relative predominance of circulating beta-hydroxybutyrate, the splanchnic productions of both beta-hydroxybutyrate and acetoacetate were approximately equal, totaling 115 g/24 h. This rate of hepatic ketogenesis was as great as that noted previously after 5-6 wk of starvation. Since the degree of hyperketonemia was about threefold greater after 5-6 wk of starvation, it seems likely that the rate of ketone-body removal by peripheral tissues is as important in the development of the increased ketone-body concentrations observed after prolonged starvation as increased hepatic ketone-body production rate. Splanchnic glucose release in this study was 123 g/24 h, which was less than that noted previously after an overnight fast, but was considerably more than that noted during prolonged starvation. Hepatic gluconeogenesis was estimated to be 99 g/24 h, calculated as the sum of lactate, pyruvate, glycerol, and amino acid uptake. This was greater than that observed either after an overnight fast or after prolonged starvation. In addition, a direct relationship between the processes of hepatic ketogenesis and gluconeogenesis was observed.

Acetoacetates↗

PubMed1978

Estimation of correlation of lactate dehydrogenase subunits mole quota based on differences in substrate inhibition.

A kinetic method of estimating the mole quota ratios of the human lactate dehydrogenase (LDH) H and M subunits based on differences in substrate inhibition of LDH isoenzymes by lactate is porposed. Stability of kinetic constants for a prolonged period of time is demonstrated. The dependence of the activity ratios on the contribution of the mole quota of the M-subunit of LDH is studied under conditions of low and high substrate concentrations. The experimental and theoretical values show the following correlation: r = 0.998; p less than 0.001. A comparison of the method proposed with the electrophoretic method of LDH subunit estimation is made, the values obtained being in good agreement. No effect of the components of human diploid cell homogenate and only an insignificant effect of the blood serum components on the kinetic constants of LDH isoenzymes are shown. The applicability of the method to the estimation of the quantitative content of both LDH subunits in natural samples is demonstrated. The informational value of the method is compared to that of other standard methods of LDH isoenzyme estimation.

Electrophoresis↗

PubMed1990

Plasma biochemical variables in response to 42-km kayak and canoe races.

Some plasma biochemical parameters were examined one day prior, immediately after and 18 h after 42-km canoe and kayak races. The increases in plasma glycerol, lactate, ammonia and uric acid as well as the elevation in plasma CK, LDH and transaminase activities confirm the changes induced by different prolonged efforts. However some differences between canoeists and kayakers were indicated for ammonia and urea plasma concentration after the race, lactate elimination and increase in CK and transaminase activities. The influence of body posture and the impact of the static component during effort are discussed as a reason for observed disparity in response to prolonged races.

Adult↗

PubMed1991

Energy metabolism in human slow and fast twitch fibres during prolonged cycle exercise.

1. The effects of prolonged exercise on energy metabolism in type I and type II muscle fibres in the vastus lateralis muscle were investigated in six male subjects (20.0 +/- 0.5 years, mean +/- S.E.M.) who performed one-legged cycling at 61% of maximum O2 consumption (VO2,max; determined with one leg) until fatigue or for a maximum of 2 h. 2. Analysis of pools of freeze-dried fibres obtained by needle biopsy and separated into specific types by the myofibrillar ATPase histochemical procedure indicated higher (P less than 0.05) lactate concentrations in type II fibres compared to type I fibres at 15 min (43.9 +/- 9.7 and 51.2 +/- 9.8 mmol (kg dry wt)-1) and at 60 min (18.2 +/- 4.7 and 25.9 +/- 6.5 mmol (kg dry wt)-1). No differences existed in lactate concentration between fibre types for pre-exercise (10.0 +/- 1.6 and 13.3 +/- 2.8 mmol (kg dry wt)-1) or post-exercise. 3. Glycogen degradation was most pronounced in type I fibres. By the end of exercise, glycogen concentration was 82.4 +/- 45 mmol glucosyl units (kg dry wt)-1 in type I fibres and 175 +/- 62 mmol glucosyl units (kg dry wt)-1 in type II fibres. 4. No significant changes in ATP and creatine phosphate (CrP) were found in either fibre type with exercise. 5. It is concluded that, at least for lactate and glycogen, fibre-specific differences are evident in prolonged submaximal exercise. The cause of the difference probably relates both to the unique energy metabolic characteristics of each fibre type and to the manner in which they are utilized during the exercise. 6. The failure to find a reduction in ATP concentration in either fibre type during prolonged exercise in the face of a progressive increase in the number of fibres showing little or no glycogen concentration suggests that protective mechanisms exist that prevent an energy crisis. The nature of these protective mechanisms remains to be elucidated.

Adenosine Triphosphate↗

PubMed2002

Alanine metabolism in acute falciparum malaria.

We investigated the integrity of the gluconeogenic pathway in severe malaria using alanine metabolism as a measure. Alanine disposition and liver blood flow, assessed by indocyanine green (ICG) clearance, were measured simultaneously in 10 patients with falciparum malaria (six severe and four moderately severe malaria). After intravenous infusion of alanine (0.3 g/kg), glucose increments (AUC0-55 min) were lower in patients with severe malaria than in those with moderately severe malaria (median = 508 vs. 808 mmol/min/l; P = 0.055). There were no significant differences in the other metabolite increments (alanine, lactate and pyruvate; P >/= 0.27). The two fatal cases had markedly delayed alanine removal (larger AUC0-55 min), prolonged T(1/2) and slower clearance (P </= 0.007). Overall the increments in blood alanine correlated directly with lactate increments (rs = 0.84; P = 0.002) and inversely with glucose (rs = -0.70; P = 0.025). Between acute and convalescent studies, the increments (AUC0-55 min) of alanine and glucose were not significantly different (P >/= 0.07) but the increments of lactate and pyruvate were lower in convalescence. Thus, the ratio of the increments of alanine to those of lactate and pyruvate were significantly higher in the convalescent study (P </= 0.017). The mean (SD) ICG clearance during acute malaria was not significantly different to that in convalescence (21.6 +/- 9.3 vs. 34.1 +/- 15.5 ml/min/kg; P = 0.25). During the acute study, there was a significant inverse correlation between ICG clearance and the post-infusion increments of lactate (rs = -0.63, P = 0.049) and pyruvate (rs = -0.74, P = 0.014). These data indicate that alanine clearance is impaired in acute falciparum malaria in proportion to the severity of illness and suggest an important role for anaerobic glycolysis in the pathogenesis of hypoglycaemia in severe malaria.

Acute Disease↗

PubMed1983

[Effect of adenosine triphosphate-magnesium chloride administration for post-ischemic acute renal failure (I)].

Models of post-ischemic acute renal failure were prepared in rats. The effects of adenosine triphosphate-magnesium chloride (ATP-MgCl2) administration following renal ischemia on possible changes in renal function and renal cellular metabolism following ischemia were studied using the model. The results obtained revealed the following: 1) Over 40 minute-renal ischemia led to significant lowerings of renal cellular ATP level and energy charge (EC) by as much as 45 to 57% and 4.1 to 7.4% of the control, respectively, at 90 min following re-establishment of renal blood flow. Significant increases in Na+ in renal tissues were observed, but no changes in K+. Further, lactate level in renal tissues tended to increase with prolonged ischemic time by as much as 27 to 31% of the control, with a renal cellular anaerobic metabolism observed. On the other hand, at 24 hr following recirculation of the kidney, plasma creatinine (P-Cr), blood urea nitrogen (BUN) and fraction excretion of sodium (FENa) increased significantly, and creatinine clearance (C-Cr) and urine osmotic pressure decreased significantly, as compared with the control, indicating ischemic acute renal failure. 2) Intravenous injection of ATP-MgCl2 at a dose of 25 mumole/kg and a rate of 1.0 mumol/min after 40 min of renal ischemia led to significant lowerings of P-Cr, BUN and FENa to 36, 35 and 35% of the control (injected with physiological saline solution), respectively, and to significant elevation of C-Cr and urine osmotic pressure by as much as 41 to 31% of the control respectively, at 24 hr after reperfusion. The above results suggested that the ischemic acute renal failure was caused by the decreases in renal cellular ATP and EC with ischemia, resulting in renal cellular metabolic disturbances. It was further suggested that ATP-MgCl2 administered for such a pathological condition could make significant improvements in renal function.

Acute Kidney Injury↗