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PubMed2003

Whale (Balaenoptera physalus) haemoglobin: primary structure, functional characterisation and computer modelling studies.

The functional properties of haemoglobin from the Mediterranean whale Balaenoptera physalus have been studied as functions of heterotropic effector concentration and temperature. Particular attention has been given to the effect of carbon dioxide and lactate since the animal is specialised for prolonged dives often in cold water. The molecular basis of the functional behaviour and in particular of the weak interaction with 2,3-diphosphoglycerate is discussed in the light of the primary structure and of computer modelling. On these bases, it is suggested that the A2 (Pro-->Ala) substitution observed in the beta chains of whale haemoglobin may be responsible for the displacement of the A helix known to be a key structural feature in haemoglobins that display an altered interaction with 2,3-diphosphoglycerate as compared with human haemoglobin. The functional and structural results, discussed in the light of a previous study on the haemoglobin from the Arctic whale Balaenoptera acutorostrata, give further insights into the regulatory mechanisms of the interactive effects of temperature, carbon dioxide and lactate.

Amino Acid Sequence↗

PubMed1996

Dynamic uncoupling and recoupling of perfusion and oxidative metabolism during focal brain activation in man.

Changes in glucose consumption, lactate production, and blood oxygenation were measured during prolonged neuronal activation (4-6 min) in human primary visual cortex using dynamic magnetic resonance spectroscopy and imaging. A decrease of steady-state glucose by 40% because of enhanced use by 21% was accompanied by a transient accumulation of lactate with a peak value of 170% 2.5 min after stimulation onset. Rapid blood hyperoxygenation indicating "uncoupling" of blood flow and oxidative metabolism was followed by a return to basal levels over 3 min. Thus, initial nonoxidative glucose consumption during functional activation is gradually complemented by a slower adjustment of oxidative phosphorylation that "recouples" perfusion and oxygen consumption at a new equilibrium.

Adult↗

PubMed1994

Immature renal tubules are resistant to prolonged anoxia.

Very few data are available regarding the decreased susceptibility of the developing kidney to anoxia. Therefore, the purpose of this study was to develop an experimental system that would allow comparison of an anoxic insult in immature and mature proximal tubule segments and to investigate the hypothesis that the developing kidney is resistant to anoxia as compared with the mature kidney. Suspensions of proximal tubules from immature (age 8-10 d) and mature (8-10 wk) rats were obtained. The purity of the tubule suspension from the immature rats was documented by villin staining. A common buffer solution was developed to compare results from the immature and mature tubules. To study the response of the tubules to anoxia, we subjected the tubule suspension from both the immature and mature rats to 15, 30, 45, and 60 min of anoxia. Lactate dehydrogenase release was measured to assess plasma membrane damage, and ATP levels were determined as an index of cellular energy. After a short anoxic insult (15 or 30 min), the percentage of lactate dehydrogenase release was not significantly different from mature tubules. After prolonged anoxia (45 and 60 min) lactate dehydrogenase release continued to increase, whereas membrane integrity stabilized in the immature tubules. ATP levels decreased in both immature and mature tubules after anoxia, but the decline of ATP was greater in the mature tubules, with a plateau at 20% of basal ATP levels as compared with 40% in the immature tubules. Therefore, the developing kidney is resistant to prolonged anoxia.

Adenosine Triphosphate↗

PubMed1993

Phenotypes associated with malignant hyperthermia susceptibility in swine genotyped as homozygous or heterozygous for the ryanodine receptor mutation.

We have examined the phenotypic expression of several parameters associated with malignant hyperthermia (MH) susceptibility in three groups (homozygous normal, homozygous abnormal and heterozygous) of Yorkshire/Duroc swine genotyped by a mutation in the ryanodine receptor. Subgroups of homozygous abnormals were classified further by the appearance or absence of muscle rigidity on prolonged in vivo challenge with halothane and suxamethonium. Four swine heterozygous for the proposed MH mutation were indistinguishable from five homozygous normal swine in temperature, heart rate, lactate concentrations, base excess and pH determined during the prolonged halothane and suxamethonium challenge. Resting creatine kinase concentrations, the in vivo barnyard challenge, the in vitro contracture response of skeletal muscle to 3% halothane and the threshold for Ca(2+)-induced Ca2+ release were also similar for subgroups of homozygous normals and heterozygotes. Therefore, inheritance of only one allele carrying the defect in the ryanodine receptor does not significantly alter phenotypes associated with MH susceptibility in this strain of swine. As four swine homozygous for the proposed MH defect did not exhibit rigidity and three of these had no other signs of MH on prolonged halothane and suxamethonium challenge, we conclude that the reported mutation in the ryanodine receptor may be necessary, but is not sufficient, for consistently eliciting the malignant hyperthermia syndrome. These findings suggest that a modulator of the syndrome may explain variability within individuals in human MH.

Animals↗

PubMed1987

Effect of vitamin A supplementation on plasma and breast milk vitamin A levels in poorly nourished Gambian women.

Plasma and breast milk vitamin A and plasma carotenoids were measured in groups of pregnant and lactating women in two neighbouring rural Gambian villages. One of the groups (Keneba) received a 650 micrograms daily vitamin A supplement. During pregnancy, plasma retinol values were significantly (19 per cent) higher in the supplemented group. During lactation, breast milk values were significantly (23 per cent) higher in the supplemented group. Changes in plasma and breast milk vitamin A levels during the cycle of pregnancy and lactation and with season are also described, and the value of a combined index of plasma retinol and plasma carotenoids is illustrated. The significant effect of a prolonged low level vitamin A supplement to pregnant and lactating women has important implications for nutrition intervention programmes.

Adult↗

PubMed1975

[Histochemical studies of the myometrium in the prolonged pregnancy].

There are several reports on the weak contractile activity of uterus in the prolonged pregnancy. Some investigations showed that the weak contractile activity is associated with the low contents of RNA, proteins and glycogen in the myometrial cell. The material was obtained from caesarean sections in 27 patients with prolonged pregnancy and 30 patients with normal pregnancy. It was found a diminished contents of glycogen and lipids in the myometrial cell, and a decreased activity of phosphorylase and alkaline phosphatase but an increased activity of acid phosphatase. The lower content of energetic material and changes in the activity of the enzymes shows that the metabolism of the myometrial cell is impaired in prolonged pregnancy. One can suppose that the lowered level of estrogens is responsible for the described changes. The lower level of estrogens probably causes the decrease of 3'5' AMP in the myometrial cell with the impaired cell metabolism as a consequence. This may be one of the causes of a weak uterine contractile activity in the prolonged pregnancy.

Acid Phosphatase↗

PubMed1975

Factors affecting the release of haemoglobin and enzymes from human erythrocytes.

The efflux of lactate dehydrogenase and haemoglobin from human erythrocytes during prolonged incubation at 37 degrees was significantly reduced by ATP, ADP, AMP, UTP, creatine phosphate, or phosphoenolpyruvate and to a lesser extent by fructose, glucose 6-phosphate or fructose 6-phosphate, but not by glucose. Iodoacetate, however, markedly increased the loss of haemoglobin and slightly increased that of lactate dehydrogenase. Phospholipase C greatly accelerated the relase of haemoglobin, lactate dehydrogenase, pyruvate kinase, hexokinase, glucose 6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase from human erythrocytes, but this effect was also reduced in the presence of ATP or ADP. The loss of lactate dehydrogenase, malate dehydrogenase, and pyruvate kinase from the cells treated with phospholipase C increased as their ATP content fell. In a series of experiments in which the action of phospholipase C was stopped by the subsequent addition of trypsin, ATP and ADP (1 mmol/l) significantly reduced the efflux of haemoglobin, but AMP had no such effect. The results are consistent with the conclusion from our previous work that enzyme leakage is related to diminution in the energy content of the cells. The protective action of AMP on cells not treated with phospholipase C, however, differs from earlier findings with rat lymphocytes and it is suggested that in red cells it might be converted into ATP or that it has a direct effect on the permeability of the cell membrane.

Adenosine Diphosphate↗

PubMed1996

Epidemiologic study of decubital ulcers in sows.

OBJECTIVE: To determine prevalence and risk factors for decubital ulcers of the shoulder in sows. DESIGN: Descriptive cross-sectional study. SAMPLE POPULATION: All females of breeding age in a large confinement swine facility. PROCEDURE: 1,916 females were examined for lesions of the skin over the tuber of the spine of the scapula and for body condition scoring. Observational data were combined with sow data (parity, date of farrowing, litter size) contained in computerized records. RESULTS: Decubital ulcers were observed in 8.3% of females, predominantly lactating sows. Ulcer prevalence was strongly associated with time after farrowing. Lesions apparently healed rapidly after weaning. Ulcer prevalence was associated with low body condition scores, but was not associated with parity. IMPLICATIONS: Decubital ulcers are a multifactorial condition. Housing on concrete floors per se did not result in ulcers. Prolonged recumbency during parturition, reduced activity in early lactation, periparturient illness, thin body condition, moist skin, and floor type are potential risk factors.

Animal Nutritional Physiological Phenomena↗

PubMed1982

Breast-feeding and family planning: a review of the relationships between breast-feeding and family planning.

A number of interrelated factors must be considered when breast-feeding is introduced as a concern for family planning programs: the number of pregnancies and births experienced, age at each pregnancy and birth, duration of the intervals between conceptions, lactation including duration and type, health and nutritional services available to meet the demands of pregnancy, delivery, and postpartum care. The dietary intake of the mother and her health and disease status have an effect on the duration of breast-feeding, and lactation has an effect on her ovulation and birth spacing. Those at particularly high risk include adolescent girls, older grand-multipara women, and families living in poverty. An historical relationship between the reduction in infant and childhood mortality and the falling off of births can be documented. The straightforward benefits on nutritional status of breast-fed infants, the conjunction with the antibody protection afforded by breast milk, served to reduce infant mortality and indirectly served to reduce birth rates. In addition, the prolongation of postpartum anovulatory cycles in breast-feeding women, coupled with sexual mores that postpone sexual relations while a women is breast-feeding in certain groups, will serve to prolong the interbirth intervals. Populations where breast-feeding is customary have been shown to have fewer births than populations where the women do not breast-fed and where infants are artificially fed.

Age Factors↗

PubMed1999

Influence of equine chorionic gonadotropin on weaning-to-estrus interval and estrus duration in early-weaned, primiparous, female swine.

The weaning-to-estrus interval (WEI) influences the total nonproductive days (NPD) accumulated by the breeding herd and affects herd productivity. Short lactation lengths (LL) are commonly followed by prolonged WEI, which are also associated with short estrus duration (ED). Equine chorionic gonadotropin treatment is a tool that has been used to reduce WEI, especially for low-parity females. The objectives for this study were to evaluate the effect of LL on the association between WEI and ED and to estimate the effects of postweaning eCG administration on WEI and ED for early-weaned females. Two treatments (TREAT) consisting of 750 IU of eCG (n = 96) or control (n = 77) were applied 1 d after weaning to first-parity, weaned females. The study was conducted on a commercial farm having a target LL of 18 d. Estrus detection was conducted three times daily, and estrus duration was determined as the interval between the first and the last positive response to back pressure. Analyses of variance were conducted to estimate the effects of LL and TREAT on WEI and the effects of TREAT and WEI on estrus duration. Mean LL was 17.9+/-1.7 d, mean WEI was 106.6+/-29.2 h, and mean estrus duration was 55.9+/-15.5 h. Even though the frequency of short WEI tended to increase with longer LL, mean WEI was shortest for females weaned after 18 d and longest for those weaned after 20 d (P<.05). The WEI for females receiving eCG (98.7+/-2.7 h) was shorter (P = .0001) than that for control females (121.5+/-3.3 h). The WEI was also affected by a LL x TREAT interaction (P = .0014), indicating that the interval was longer (P<.05) for control females weaned after 17 and 20+ d than for other females. The LL and TREAT did not affect estrus duration (P = .20 and P = .157, respectively). However, estrus duration was reduced as the WEI increased (P = .0001), and it was also influenced by a WEI x TREAT interaction (P = .024). A linear regression model estimated that the association between WEI and estrus duration was stronger in the eCG group than in the control group (R2 = .51 and .15, respectively; both P<.001). In conclusion, the use of eCG postweaning was associated with more precise prediction of estrus duration as a function of the WEI and allows optimization of breeding management in early-weaned, primiparous females.

Animals↗

PubMed1983

Phosphoglycerate kinase deficiency: another cause of recurrent myoglobinuria.

A 14-year-old boy had myoglobinuria and renal failure after intense exercise; a year earlier he had experienced a milder episode. There was no consanguinity and no family history of neuromuscular diseases or hemolytic anemia. Strength was normal. Forearm ischemic exercise caused prolonged contracture with no rise of venous lactate. Muscle morphology showed only a mild increase of lipid droplets. Glycogen concentration was normal. Muscle phosphoglycerate kinase (PGK) activity was 5% of the normal mean, and all other glycolytic enzymes were normal. The residual PGK activity of muscle was heat stable but showed slower than normal electrophoretic mobility and decreased Michaelis constants for 3-phosphoglycerate and adenosine triphosphate. The enzyme defect was also expressed in erythrocytes and in fibroblast and muscle cultures. PGK activity was decreased in tissues from the patient's mother but normal in the father. PGK deficiency is an X-linked recessive trait usually associated with hemolytic anemia, mental retardation, and seizures; myopathy had not been recognized previously. Muscle PGK deficiency is now added to two other newly recognized glycolytic defects, phosphoglycerate mutase and lactate dehydrogenase deficiencies, as a cause of recurrent myoglobinuria.

Acute Kidney Injury↗

PubMed1991

Reflex control of magnocellular vasopressin and oxytocin secretion.

Reflex control of magnocellular vasopressin and oxytocin secretion has captured the curiosity and investigative imagination of neuroendocrinologists for nearly 50 years. While it may seem obvious that brisk elevations in circulating levels of vasopressin in response to hemorrhage, or of oxytocin in response to suckling, must of necessity arise from magnocellular neurosecretory neurons in the hypothalamus, the central pathways mediating these reflexes have, until quite recently, remained elusive. In this brief review, ongoing attempts to delineate these pathways are summarized. Evidence for plasticity and local modulation of magnocellular reflexes in response to prolonged stimulation, such as chronic dehydration and lactation, is also presented.

Animals↗

PubMed2004

Clinical picture, diagnosis, treatment and outcome of severe acute respiratory syndrome (SARS) in children.

Children are susceptible to infection by SARS-associated coronavirus (SARS-CoV) but the clinical picture of SARS is milder than in adults. Teenagers resemble adults in presentation and disease progression and may develop severe illness requiring intensive care and assisted ventilation. Fever, malaise, cough, coryza, chills or rigor, sputum production, headache, myalgia, leucopaenia, lymphopaenia, thrombocytopaenia, mildly prolonged activated partial thromboplastin times and elevated lactate dehydrogenase levels are common presenting features. Radiographic findings are non-specific but high-resolution computed tomography of the thorax in clinically suspected cases may be an early diagnostic aid when initial chest radiographs appear normal. The improved reverse transcription-polymerase chain reaction (RT-PCR) assays are critical in the early diagnosis of SARS, with sensitivity approaching 80% in the first 3 days of illness when performed on nasopharyngeal aspirates, the preferred specimens. Absence of seroconversion to SARS-CoV beyond 28 days from disease onset generally excludes the diagnosis. The best treatment strategy for SARS among children remains to be determined. No case fatality has been reported in children and the short- to medium-term outcome appears to be good. The importance of continued monitoring for any long-term complications due to the disease or its empiric treatment, cannot be overemphasised.

Antiviral Agents↗

PubMed2002

Epidemiology of the American Indians' burden and its likely genetic origins.

It was not known until recently whether the endemic of cholesterol gallstones among certain southwestern American Indian tribes was unique among this ethnic group. With use of ultrasonography of the gallbladder and standard diagnostic criteria, gallstones are now found in epidemic proportions in 13 diverse American Indian tribes and communities living in Arizona, Oklahoma, and the Dakotas. We speculate that this predisposition is polygenic involving "thrifty" genes that conferred survival advantages when Paleo-Indians migrated from present-day Siberia to the Americas during the last Great Ice Age approximately 50,000 to 10,000 years ago. A reasonable hypothesis is that functioning of these genes promoted more efficient calorie utilization and storage in the form of adipose tissue. Beneficial results would have been operative during the isolation of Paleo-Indians in the Bering Strait land bridge (Beringia) when thrifty genes would have ensured sufficient fat reserves for survival of prolonged winters, successful pregnancy outcomes, and extended lactation periods. The authors' conjoint work on genetics of experimental cholesterol cholelithiasis in inbred mice promises help in pinpointing orthologous genetic loci (LITH genes) in the human genome. Moreover, the shared environments and homogeneity of American Indian tribes and communities should facilitate discovery of the ensembles of their common and rarer cholesterol gallstone genes. It is anticipated that knowledge of expression, polymorphisms, and functionality of LITH genes will help resolve the molecular mechanisms of this complex heterogeneous trait and thereby provide targets for novel therapies to prevent cholesterol cholelithiasis worldwide.

Cholelithiasis↗

PubMed2002

Prolonged mild hypothermia after experimental hypothermic circulatory arrest in a chronic porcine model.

OBJECTIVES: We sought to evaluate the potential efficacy of prolonged mild hypothermia after hypothermic circulatory arrest. METHODS: Twenty pigs, after a 75-minute period of hypothermic circulatory arrest, were randomly assigned to be rewarmed to 37 degrees C (normothermia group) or to 32 degrees C and kept at that temperature for 14 hours from the start of rewarming (hypothermia group). RESULTS: The 7-day survival was 30% in the hypothermia group and 70% in the normothermia group (P =.08). The hypothermia group had poorer postoperative behavioral scores than the normothermia group. Prolonged hypothermia was associated with lower oxygen extraction and consumption rates and higher mixed venous oxygen saturation levels during the first hours after hypothermic circulatory arrest. Decreased cardiac index, lower pH, and higher partial pressure of carbon dioxide were observed in the hypothermia group. There was a trend for beneficial effect of prolonged hypothermia in terms of lower brain lactate levels until the 4-hour interval and of intracranial pressure until the 10-hour interval. Postoperatively, total leukocyte and neutrophil counts were lower, and creatine kinase BB was significantly increased in the hypothermia group. At extubation, the hypothermia group had higher oxygen extraction rates and lower brain tissue oxygen tension. CONCLUSIONS: A 14-hour period of mild hypothermia after 75-minute hypothermic circulatory arrest seems to be associated with poor outcome. However, the results of this study suggest that mild hypothermia may preserve its efficacy when it is used for no longer than 4 hours, but the potentials of a shorter period of postoperative mild hypothermia still require further investigation.

Animals↗

PubMed2000

Opening of the mitochondrial permeability transition pore causes depletion of mitochondrial and cytosolic NAD+ and is a causative event in the death of myocytes in postischemic reperfusion of the heart.

The opening of the mitochondrial permeability transition pore (PTP) has been suggested to play a key role in various forms of cell death, but direct evidence in intact tissues is still lacking. We found that in the rat heart, 92% of NAD(+) glycohydrolase activity is associated with mitochondria. This activity was not modified by the addition of Triton X-100, although it was abolished by mild treatment with the protease Nagarse, a condition that did not affect the energy-linked properties of mitochondria. The addition of Ca(2+) to isolated rat heart mitochondria resulted in a profound decrease in their NAD(+) content, which followed mitochondrial swelling. Cyclosporin A(CsA), a PTP inhibitor, completely prevented NAD(+) depletion but had no effect on the glycohydrolase activity. Thus, in isolated mitochondria PTP opening makes NAD(+) available for its enzymatic hydrolysis. Perfused rat hearts subjected to global ischemia for 30 min displayed a 30% decrease in tissue NAD(+) content, which was not modified by extending the duration of ischemia. Reperfusion resulted in a more severe reduction of both total and mitochondrial contents of NAD(+), which could be measured in the coronary effluent together with lactate dehydrogenase. The addition of 0.2 microm CsA or of its analogue MeVal-4-Cs (which does not inhibit calcineurin) maintained higher NAD(+) contents, especially in mitochondria, and significantly protected the heart from reperfusion damage, as shown by the reduction in lactate dehydrogenase release. Thus, upon reperfusion after prolonged ischemia, PTP opening in the heart can be documented as a CsA-sensitive release of NAD(+), which is then partly degraded by glycohydrolase and partly released when sarcolemmal integrity is compromised. These results demonstrate that PTP opening is a causative event in reperfusion damage of the heart.

Animals↗

PubMed1977

Hormonal and metabolic responses to glucagon in diabetes mellitus.

The metabolic and hormonal responses to glucagon (1 mg, subcutaneous) were studied in twelve diabetic and twelve non-diabetic subjects. Diabetics showed a GH response, which although commencing slightly earlier, did not otherwise differ from that of the controls. There was the expected diminished insulin response to glucagon among the patients on oral agents. The GH response to glucagon in the diabetics began before there was any significant fall in blood glucose (BG). The hyperglycaemic response in the diabetics peaked later, was greater in amplitude and was more prolonged. In this group both pyruvate and lactate changes were delayed and diminished in amplitude. The diabetics showed a biphasic response of both acetoacetate and 3-hydroxybutyrate to glucagon; a small transient significant rise in the first 2 h followed by a second rise after 3h. In contrast the controls showed a significant fall in these metabolites during the initial 2 h, before a rise after 3 h. The significance of these hormonal and metabolic responses is discussed.

Acetoacetates↗

PubMed2003

Comparison of autologous and allogeneic hematopoietic stem cell transplantation for follicular lymphoma.

In this article, we report on 904 patients undergoing transplantation for follicular lymphoma. A total of 176 (19%) received allogeneic, 131 (14%) received purged autologous, and 597 (67%) received unpurged autologous transplants. Five-year treatment-related mortality (TRM) rates were 30%, 14%, and 8% and 5-year recurrence rates were 21%, 43%, and 58% after allotransplantation, purged autotransplantation, and unpurged autotransplantation, respectively. In multivariate analyses, allotransplantation had higher TRM and lower disease recurrence. Purged autotransplantation had a 26% lower recurrence risk than unpurged autotransplantation. Five-year probabilities of survival were 51%, 62%, and 55% after allogeneic, purged autotransplantation, and unpurged autotransplantation, respectively. Advanced age, prolonged interval from diagnosis to transplantation, high lactate dehydrogenase (LDH), refractory disease, bone marrow involvement, low performance scores, and transplantation between 1990 and 1993 were associated with adverse outcomes. Total body irradiation was associated with higher TRM but lower recurrence. There was no association between acute or chronic graft-versus-host disease and recurrence after allotransplantation. We conclude that both allogeneic and autologous transplantation can induce durable remissions. There may be a benefit to graft purging in autologous transplantation. The decreased recurrence after allotransplantation is offset by increased TRM. We did not detect a correlation between graft-versus-host disease (GVHD) and recurrence. Finally, outcomes of transplantation for follicular lymphoma show improvement over the past decade.

Adult↗