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PubMed2004

Abnormal blood lactate accumulation after exercise in patients with multiple mitochondrial DNA deletions and minor muscular symptoms.

STUDY OBJECTIVES: Muscle is one of the most commonly affected organs in mitochondrial disorders, and the symptoms are often exercise related. The cardiopulmonary exercise test with the determination of lactic acid formation could give supplementary information about the exercise-induced metabolic stress and compensatory mechanisms used in these disorders. The aim of this study was to evaluate the exercise capacity and lactate kinetics related to exercise in subjects with two genetically characterized mitochondrial disorders (multiple mitochondrial DNA deletions with PEO, MELAS) compared with lactate kinetics in subjects with metabolic myopathy (McArdle's disease) and in the healthy controls. DESIGN: The subjects were consecutive, co-operative patients of Department of Neurology of Helsinki University Hospital. Molecular genetic analyses were used for group classification of the mitochondrial myopathy. STUDY SUBJECTS: The study groups consisted of 11 patients with multiple deletions (PEO) and five patients with a point mutation in the mitochondrial DNA (MELAS), four patients with a muscle phosphorylase enzyme deficiency (McArdle's disease) and 13 healthy controls. The clinical disease of the patients was relatively mild. MEASUREMENTS AND RESULTS: A graded exercise test with ventilatory gas analyses and venous blood lactic acid analyses was performed. The main finding was the prolonged accumulation of blood lactate after the exercise in the PEO and MELAS groups compared with the controls. An overcompensation in ventilation was found in the MELAS and PEO group. CONCLUSIONS: The blood lactate accumulation after exercise occurs in patients with multiple mitochondrial DNA deletions or MELAS even in patients with only mild exercise intolerance. Cardiopulmonary exercise can be used in the diagnostic process of patients with mitochondrial myopathies.

Adult↗
PubMed1990

In vitro culture of cryopreserved bovine mammary cells on collagen gels: synthesis and secretion of casein and lactoferrin.

The preparation, cryopreservation, and culture on type I collagen gels of lactating bovine mammary cells with prolonged milk protein synthesis and secretion in vitro is described. Cryopreserved cells prepared as acinar fragments from either lactating or developing mammary glands attached to the collagen substratum within 24-48 hr after plating in serum and hormone supplemented medium. During continued culture in hormone-supplemented (insulin, cortisol, and prolactin) serum-free medium outgrowth of cells from the attached acinar fragments was observed beginning on day 2, with continued outgrowth to near confluence by day 6. Two morphologically distinct cell types were evident; initial outgrowth was by large polygonal cells that were subsequently overlain by spindle-shaped cells. Cells from both lactating and developing mammary glands sustained substantial milk protein secretion for at least 14 days in culture. Alpha S1-casein synthesis and secretion in cultures of lactating mammary cells was dependent on a critical minimum cell population density, below which alpha S1-casein was not secreted. In contrast, lactoferrin (LF) secretion into the medium increased linearly with the increase in cell population density. Cells cryopreserved up to 16 months secreted LF at levels comparable to fresh cultures of the same cells.

Animals↗
PubMed1990

Stability of brain intracellular lactate and 31P-metabolite levels at reduced intracellular pH during prolonged hypercapnia in rats.

The tolerance of low intracellular pH (pHi) was examined in vivo in rats by imposing severe, prolonged respiratory acidosis. Rats were intubated and ventilated for 10 min with 20% CO2, for 75 min with 50% CO2, and for 10 min with 20% CO2. The maximum PaCO2 was 320 mm Hg. Cerebral intracellular lactate, pHi, and high-energy phosphate metabolites were monitored in vivo with 31P and 1H nuclear magnetic resonance (NMR) spectroscopy, using a 4.7-T horizontal instrument. Within 6 min after the administration of 50% CO2, pHi fell by 0.57 +/- 0.03 unit, phosphocreatine decreased by approximately 20%, and Pi increased by approximately 100%. These values were stable throughout the remainder of the hypercapnic period. Cerebral intracellular lactate, visible with 1H NMR spectroscopy in the hyperoxic state, decreased during hypercapnia, suggesting either a favorable change in oxygen availability (decreased lactate production) or an increase in lactate clearance or both. All hypercapnic animals awakened and behaved normally after CO2 was discontinued. Histological examination of cortical and hippocampal areas, prepared using a hematoxylin and eosin stain, showed no areas of necrosis and no glial infiltrates. However, isolated, scattered, dark-staining, shrunken neurons were detected both in control animals (no exposure to hypercapnia) and in animals that had been hypercapnic. This subtle histological change could represent an artifact resulting from imperfect perfusion-fixation, or it could represent subtle neurologic injury during the hypercapnia protocol. In summary, extreme hypercapnia and low pHi (approximately 6.5) are well tolerated in rats for periods up to 75 min if adequate oxygenation is maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Respiratory↗
PubMed2006

Renal cortical necrosis related to paraneoplastic antiphospholipid syndrome.

Acute bilateral renal cortical necrosis is a very rare cause of acute renal failure. We report here for the first time a case related to antiphospholipid syndrome, paraneoplastic of a lung neoplasia. A 46-year-old male smoker without medical history was admitted for acute dyspnea and anuria. Biological examination showed acute renal failure associated with hyperkalemia, high serum lactate dehydrogenase level, and prolonged activated thrombin time (ratio 1.29). Chest radiograph showed a right laterotracheal round lesion. A percutaneous left renal biopsy showed cortical necrosis, and renal arteriography confirmed bilateral cortical necrosis. Blood examination showed antiphospholipid antibodies type anticardiolipin. Chest computed tomographic scan confirmed the presence of a lung tumor. Two years after tumor surgery, the patient was still anuric and on long-term hemodialysis therapy, but antiphospholipid antibody results were negative. This case describes the first association of antiphospholipid syndrome to epidermoid lung cancer, shown by cortical bilateral necrosis. It also emphasizes the utility of renal biopsy in case of an unusual acute renal failure.

Acute Kidney Injury↗
PubMed1995

Possible modulation of adipose tissue responsiveness to catecholamines by available dietary protein in dairy cows during early lactation.

Early lactation is characterised by a number of metabolic adaptations which divert nutrients from the peripheral tissues in favour of the mammary gland. One such adaptation is the increased responsiveness of adipose tissue to lipolytic stimuli. The effects of the condition score at calving and the level of undegradable protein in the diet on the responsiveness of adipose tissue to adrenergic stimulation were studied in dairy cows during early lactation. They were subjected to exogenous epinephrine challenges on weeks 3 and 8 of lactation. The responsiveness to epinephrine increased with high levels of rumen undegradable protein in the diet and a high condition score at calving, with no interaction between the 2 factors. The responsiveness to epinephrine was increased by the dietary treatment, especially on the 8th week of lactation, which suggests that the availability of protein might prolong the metabolic adaptations characteristic of early lactation.

Adipose Tissue↗
PubMed1991

Contraceptive use and breast-feeding duration in rural Bangladesh.

The association between contraceptive use and breast-feeding duration was investigated in 2380 women in rural Bangladesh where women usually stop breast-feeding once pregnant. Life table analysis showed that women receiving regular injections of depo medroxy progesterone acetate (DMPA) and those using non-hormonal contraception breast-fed significantly longer than women using no contraception. In contrast, women using oral contraceptives (combination of 0.5 mg norgestrel and 0.05 mg ethinyl oestradiol) did not breast-feed longer than women using no contraception. It is suspected that prolongation of breast-feeding obtained by delaying the next pregnancy with this oral contraceptive was offset by the depressing effect of oestradiol on lactation. Thus, in communities where prolonged breast-feeding is associated with improved child survival, non-hormonal contraceptive methods, or injectable DMPA, should be preferred for lactating women to oestrogen-containing oral contraceptives.

Bangladesh↗
PubMed2002

Impact of lactational performance on bone mineral density in marginally-nourished Bangladeshi women.

This cross-sectional study, carried out during July 1997-June 1998, evaluated the effects of prolonged breast-feeding and lactational amenorrhoea on bone mineral density (BMD) in 400 marginally-nourished Bangladeshi women aged 20-81 years. A bone densitometer was used for measuring BMD in the distal and ultra-distal end of radius and ulna. The results showed that the women who breastfed for 60 months or less had a higher mean BMD compared to those who breastfed for 61-120 months and for over 120 months. There was a significantly higher BMD in the women who had a shorter duration of lactational amenorrhoea compared to those having a longer duration of lactational amenorrhoea. BMD was significantly and negatively correlated with total duration of lactational amenorrhoea (slope -0.024, p<0.05) after controlling for parity, physical workload, and total duration of breast-feeding. The study concluded that there was a negative correlation between longer duration of breast-feeding and BMD, but it was not found when other factors were controlled in multivariate analysis. The duration of lactational amenorrhoea, which is a proxy indicator of breast-feeding, showed a negative correlation with BMD. It is recommended that all lactating women be given diet with adequate calcium to support breast-feeding for maintaining good nutrition of their bones.

Adult↗
PubMed1990

Physiological responses during prolonged exercise at the power output corresponding to the blood lactate threshold.

Heart rate (HR) and oxygen uptake (VO2) at the mechanical power (W) corresponding to the capillary blood lactate ([la]cap) of 4 mmol.l-1 (Wlt) were measured in 34 healthy male subjects during incremental exercise (Winc). On the basis of these measurements, the subjects were asked to cycle at Wlt for 60 min (steady-state exercise, Wss). Twenty subjects could not reach the target time (mean exhaustion time, te, 38.2 min, SD 5.3), while 6 of the 14 remaining subjects declared themselves exhausted at the end of exercise. The final [la]cap if the two groups of exhausted subjects were 5.3 mmol.l-1, SD 2.3 and 4.3 mmol.l-1, SD 1.1, respectively. At the end of Wss, [la]cap and HR were significantly lower in the 8 unexhausted subjects than in the other subjects. This group also had a lower HR at Wlt during Winc. The HR and VO2 appeared to be higher during Wss than during Winc. When all subjects were ranked according to their te during Wss, Wlt (expressed per kilogram of body mass) was found to be negatively related to te. In conclusion, during Winc, measurements of physiological variables at fixed [la]cap give a poor prediction of their trends during Wss and of the relative te; at the same work load [la]cap can be quite different in the two experimental conditions. Furthermore, resistance to exercise fatigue at Wlt seems lower in the fitter subjects.

Adult↗
PubMed1996

Pattern of organ failure following severe trauma.

Multiple organ failure (MOF) is considered to be the leading cause of death after severe trauma. Although there is extensive literature on MOF, little is known about the pattern, sequence, and onset of this clinical syndrome. The first goal of this clinical study was to define MOF; the second was to assess the typical onset, sequence, and pattern of MOF; and the third was to define certain risk factors for the development of MOF in 342 multiple trauma patients. Patients with an Injury Severity Score (ISS): > 20 (mean 35.7) were included. Three well established MOF scoring methods were used to give strict definitions of MOF: 11.4% of the total patient population developed MOF, and 88.6% did not. Respiratory failure was most frequent in patients developing MOF (74.4%), and these patients had the highest mortality rate (65.5%) compared to patients with failure of other organ systems (liver, cardiovascular system). Generally, the lung is the first organ to fail after injury (failure after 3.7 +/- 2.8 days). Significant renal failure and the need for dialysis decreased to < 5%; other signs of organ dysfunction (gastric, central nervous system) are difficult to verify. Typical risk factors for the development of MOF after severe trauma are the severity, type, and distribution of injury as well as the indicators of prolonged hemorrhagic shock (elevated lactate levels). The main therapeutic efforts, therefore, should be the effective treatment of traumatic hemorrhagic shock during the initial phase, adequate resuscitation, optimal oxygenation, and early surgical treatment.

Adolescent↗
PubMed2006

Skeletal muscle expression of LDH and monocarboxylate transporters in growing rats submitted to protein malnutrition.

BACKGROUND: In different circumstances such as infant malnutrition, old age or chronic disease, decline of muscular strength, particularly anaerobic power, is shown. In this context, our laboratory, has demonstrated a decrease in anaerobic glycolytic power in pre-pubertal Bolivian children living at low and high altitude and suffering from marginal protein malnutrition. AIM OF THE STUDY: To bring molecular support to the relationship between protein malnutrition and anaerobic glycolytic metabolism, we studied the impact of prolonged protein malnutrition on lactate metabolism in different muscles of growing rats. Lactate dehydrogenase (LDH), monocarboxylate transporters (MCT1, MCT4) and membrane protein CD147 were chosen as specific markers of anaerobic glycolytic metabolism. METHODS: Two groups of 10 weaning male rats were fed for 10 weeks either ad libitum with a well-balanced diet containing 18% protein or an isocaloric-diet containing 8% protein. LDH activity and mRNA amounts of LDH isoforms, MCT, CD147 were measured. RESULTS: Protein deprivation during rat growth induced a decrease of LDH specific activity in skeletal muscles (mean value of -41%), accompanied by isoform distribution modifications in soleus, but not in glycolytic muscles (extensor digitorum longus (EDL) or plantaris). A reduction in mRNA amounts encoding the LDH A and B subunits was observed in EDL. A decrease in LDH B mRNA amounts was monitored in plantaris, whereas no modification in both LDH isoform mRNA quantities was observed in soleus. MCT1 mRNA quantities were decreased in EDL but MCT4 mRNA quantities remained stable. CD147 mRNA amounts were unchanged except for EDL with a 42% increase. CONCLUSIONS: The global decreases of LDH activity, LDH and MCT gene expressions in growing rat skeletal muscles support the observed alterations of lactate metabolism associated with lowered muscular anaerobic performances in protein malnutrition.

Animals↗
PubMed2001

Prolonged stage duration during incremental cycle exercise: effects on the lactate threshold and onset of blood lactate accumulation.

The aim of this study was to investigate whether increasing the duration of workloads from 3 min to 8 min during incremental exercise would influence workload (W), oxygen consumption (VO2) and heart rate (HR) at the lactate threshold (LT) and the onset of blood lactate accumulation (OBLA). Two groups of six male cyclists were assigned to a well-trained (WT) and recreational (REC) group on the basis of their performance in a maximal incremental ramp test. Each subject then performed two incremental lactate tests (EXT) consisting of six workloads of either 3 min (EXT3-min) or 8 min (EXT8-min) duration. At the completion of each workload whole capillary blood samples were obtained for the determination of blood lactate (BLa) concentration (mM). Power output (Watts, W), HR and VO2 were averaged in the final minute of each workload as well as in the third minute of the EXT8-min. The workload, HR and VO2 at the LT and OBLA were subsequently determined from the data of EXT3-min and EXT8-min. The results demonstrate that workload and VO2, but not HR, at the LT and OBLA were higher in the WT cyclists. At the same time, the workload at the LT obtained from the results of the EXT3-min was significantly (P < 0.05) higher then the value obtained in the EXT8-min in the WT subjects but not the REC subjects. However, the workload, VO2 and HR at the OBLA, together with the VO2 and HR at the LT were not significantly different when calculated from data obtained from EXT3-min or EXT8-min. The data obtained in this study suggest that incremental exercise protocols using workloads of duration longer than 3 min have the effect of increasing the workload at the LT in well-trained cyclists. However, the OBLA determined in exercise tests using stage increments of either 3 min or 8 min is similar in cyclists of different training status.

Adaptation, Physiological↗
PubMed1975

Nippostrongylus brasiliensis: further properties of antibody-damaged worms and induction of comparable damage by maintaining worms in vitro.

When adult Nippostrongylus brasiliensis were maintained in vitro they became damaged. Using the criteria of ultrastructural morphology, acetylcholinesterase isoenzyme pattern and the behaviour of the worms after transfer to a normal rat, this damage appeared to be similar to that produced by the in vivo action of antibodies. Antibodies were shown to be responsible for the anterior migration of adult worms which occurs during primary infections in mature rats and in the prolonged infections seen in lactating and immature rats. Antibody damaged worms and worms unaffected by antibodies were equally able to stimulate the immune response required for worm expulsion. Apparently antibody damage is not required for the initiation of the second immune component necessary for expulsion of this parasite.

Acetylcholinesterase↗
PubMed2003

The impact of tick control on the productivity of indigenous cattle under ranch conditions in Uganda.

The impact of tick control on the productivity of indigenous cattle was investigated in three herds of East African shorthorn Zebu and Zebu x Ankole (Nganda) breeds, maintained under three tick management systems practised under ranch conditions: twice-a-week dipping, once-a-month dipping, and no tick control. The milk production and the growth rates of pre-weaned and post-weaned calves were monitored once a month over a period of 34 months. Milk offtake was 23% higher during the heavy rainy seasons than in the long dry seasons. Twice-a-week dipping increased the milk offtake by 21% in the second year of study and prolonged the duration of lactation in cows. Similarly, twice-a-week dipping increased the pre-weaning growth rate by 39% in the second year of study, but had no significant effect on the post-weaning growth rate. Generally, the growth rate of calves were greatest during the heavy rainy seasons and least during the long dry seasons. These results provide a basis for assessing the losses under different tick management systems in the various production systems.

Administration, Topical↗
PubMed1987

High dose intravenous gammaglobulin in Coombs positive hemolytic anemia.

Four patients with warm type autoimmune hemolytic anemia who failed to respond to steroid therapy received high dose intravenous gammaglobulin (0.2-0.4 g/kg daily) for five days. In one patient hemolysis occurred in association with non-Hodgkin's lymphoma and in the others the cause of the hemolysis was not established; two patients had prior splenectomy. A response to gammaglobulin therapy, demonstrable by a rise in or stabilisation of hemoglobin levels, a decrease in elevated serum bilirubin and lactate dehydrogenase levels, or prolongation of a shortened red cell (51Cr) survival, was observed in three patients. In two of these patients the effect of gammaglobulin therapy was temporary but allowed for splenectomy to proceed in one patient, without blood transfusion. The third patient continued to improve after cessation of gammaglobulin treatment. These findings suggest that high dose intravenous gammaglobulin may temporarily ameliorate hemolysis in some individuals with warm type immune hemolytic anemia, and may be a useful adjunct to steroids immediately before splenectomy.

Adult↗
PubMed1999

An analysis of breastfeeding patterns and menses returning in Chengdu, China.

OBJECTIVE: To study the relationship between infant feeding practices and the duration of lactational amenorrhea, WHO conducted a multi-centered prospective study in 7 countries from 1989. This paper reports the preliminary results based on the data collected in Chengdu center in China. METHODS: A detailed follow-up survey was conducted among 541 pairs of mothers and infants from delivery to the returning of menses of mothers at the interval of every 2 weeks. RESULTS: The results showed that the mean number of breastfeeding episodes and mean duration of breastfeeds had little correlation with the time since delivery. Within 6 months since delivery, the percentage of infants' feeds consisting of breastmilk was over 90%, and this percentage dropped to 70% at 1 year's age of infants. The time to the start of regular supplementation was 153 days postpartum. The proportion of women in exclusive breastfeeding at 2 weeks postpartum was 73.4%, and these figures at 3 and 6 months postpartum were about 60% and 40%, respectively. Until 18 months postpartum, nearly 80% mothers were partial breastfeeding their infants. The cumulative probabilities of menses returning were 0.0150, 0.0395, 0.2345 and 0.6820 at 61, 89, 187 and 369 days postpartum respectively. The median duration of lactational amenorrhea was 282 days. CONCLUSION: These results indicated that the duration of lactational amenorrhea would be prolonged if the time of exclusive/predominant breastfeed was extended and the supplementary food was introduced later. The paper concluded that the first menses returning was the signal for initiating contraceptive methods for women.

Adult↗
PubMed1976

Gastric H+ secretion in presence of substrates: absolute dependence on secretagogues.

Spontaneously secreting gastric mucosae of the bullfrog (Rana catesbeiana) were brought to resting states in the absence of both the exogenous secretagogue and energy-yielding substrate, either by treatment with burimamide or by the classical method of prolonged preincubation. Glucose, pyruvate, lactate, and tricarboxylic acid cycle intermediates were compared with short- and long-chain fatty acids as potential substrates on these resting mucosae to determine if the latter could initiate and sustain H+ secretion in the absence of added secretagogues. The experimental data indicate that fatty acids cannot stimulate acid secretion from the resting state by preempting the requirement for secretagogues. Although fatty acids may serve as preferred substrates in comparison with glucose, glycolytic intermediates, and tricarboxylic acid cycle intermediates, acid secretion is obligatorily dependent on the presence of endogenous or added secretagogues. The implications of this finding with respect to one of the recently proposed hypothesis for secretagogue regulation of gastric hydrochloric acid secretion are discussed.

Animals↗
PubMed1985

Dopamine blockade reverses the inhibition of prolactin which results from intrahypothalamic pituitary grafts.

When mated with fertile bucks, rats with anterior pituitary (AP) tissue grafted into the hypothalamus did not exhibit prolongation of the diestrous cycle. Treatment of these rats with alpha-methyl-p-tyrosine, reserpine, or haloperidol for 1 or 2 days after mating increased the interestrous interval by a few days in all rats and to more than 8 days (leading to pseudopregnancy or pregnancy) in 20% of the cases. The same treatment in unmated normals resulted in 80% becoming pseudopregnant. To get more than 70% of rats with hypothalamic AP grafts pregnant or pseudopregnant required dopamine-blocking drugs for 3 or 4 consecutive days. Pregnancy was prolonged in 50% and lactation was impaired in 78% of the grafted rats which littered. Both impairments, like the original failure of the luteotrophic response, are attributed to the effects of PRL autofeedback from the hypothalamic AP grafts. These experiments provide further evidence that the mechanism whereby PRL in the hypothalamus inhibits PRL secretion involves elevation of dopamine.

Animals↗