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PubMed1980

Lactate dehydrogenase in tears.

Lactate dehydrogenase levels in tears were measured in normal subjects and in patients with retinoblastoma. When specimens were collected without trauma in normal subjects, there were usually no detectable levels of lactate dehydrogenase. When the eyelids were rubbed (probably liberating epithelial cells) lactate dehydrogenase levels were detectable and were five to ten times those of normal aqueous humor. When lactate dehydrogenase isoenzymes in such specimens were analyzed, the level of lactate dehydrogenase 5 was always higher than that of lactate dehydrogenase 1 (similar to normal aqueous humor). While occasional patients with retinoblastoma do have elevated levels of lactate dehydrogenase in tears, it is uncertain if this is due to epithelial destruction or retinoblastoma itself. Lactate dehydrogenase in tears does not appear to be a useful test for the diagnosis of retinoblastoma given present techniques for collection and analysis.

Child↗
PubMed2002

Resistin and RELM-alpha gene expression in white adipose tissue of lactating mice.

The adipose tissue-derived factor resistin has been suggested to induce insulin resistance in obesity and inhibit adipocyte differentiation. Lactation is associated with major metabolic adaptations, which cause a profound loss of adipose tissue to support milk production by the mammary gland. This study has examined the expression of the resistin and resistin-like molecule-alpha (RELM-alpha) genes in white adipose tissue of lactating mice. Lactation induced significant increases in food intake and body weight, whereas body fat was substantially decreased at peak lactation. Resistin and RELM-alpha mRNAs were both detectable in gonadal, subcutaneous, and mammary gland fat; mRNA level was highest in gonadal fat and lowest in mammary tissue. There was no difference in resistin mRNA level in gonadal fat of lactating mice compared with controls. However, RELM-alpha mRNA fell by approximately 40% in early lactation and there was a parallel fall in the leptin mRNA level proportional to the loss of fat mass. These results indicate that the substantial reduction of adiposity in lactation does not lead to any changes in resistin gene expression; however, the fall in RELM-alpha mRNA might indicate a role for RELM-alpha in the metabolic adaptations of lactation.

Adipose Tissue↗
PubMed1996

Region-specific reduction in stress-induced c-fos mRNA expression during pregnancy and lactation.

Hypothalamo-pituitary-adrenal (HPA) responses to stress are dramatically attenuated during lactation. To examine whether this is due to diminished stress-induced activation of specific areas of the brain involved in HPA responses, c-fos mRNA expression was employed as a marker of stress-induced neuronal activation. Regional levels of expression were quantified in female rats exposed to 30 min immobilisation stress during late pregnancy (days 19-21), early lactation (days 3-4) and mid-lactation (days 10-14), and compared with the levels in virgin females. Stress-induced levels of corticosterone were significantly lower in late pregnant and early lactating rats compared with the levels in virgin females, and this correlated with a marked attenuation of stress-induced c-fos mRNA expression in the parvocellular division of the PVN. This reduced activation suggests that neuroendocrine hyporesponsiveness during lactation may arise from an effect on afferent pathways to the PVN. Extrahypothalamic areas known to be important for HPA activation displayed three patterns of c-fos mRNA expression: (i) in the ventral tegmental area, dorsal vagal complex, pyriform cortex and all areas of the hippocampus (CA1, CA2, CA3, dentate gyrus), expression levels did not vary significantly with reproductive status; (ii) in the locus coeruleus (A6 catecholaminergic group), a peak of expression was detected in late pregnant animals; and (iii) in the medial amygdala, ventral part of the lateral septum and cingulate cortex expression was significantly reduced in pregnant and lactating animals, with a nadir in early lactation. The decreased expression of c-fos mRNA in these latter areas correlated with that in the parvocellular PVN, and suggests that their interaction may contribute to the reduced neuroendocrine responses of lactating rats.

Animals↗
PubMed1999

Redistribution of protein kinase C isoforms in rat pancreatic acini during lactation and weaning.

Freshly enzymatically isolated pancreatic acini from lactating and weaning Wistar rats were used to investigate the role of protein kinase C (PKC) isoforms during these physiologically relevant pancreatic secretory and growth processes. The combination of immunoblot and immunohistochemical analysis shows that the PKC isoforms alpha, delta, and epsilon are present in pancreatic acini from control, lactating and weaning rats. A vesicular distribution of PKC-alpha, -delta, and -epsilon was detected by immunohistochemical analysis in the pancreatic acini from all the experimental groups. PKC-delta showed the strongest PKC immunoreactivity (PKC-IR). In this vesicular distribution, PKC-IR was located at the apical region of the acinar cells. No differences were observed between control, lactating and weaning rats. However, the immunoblot analysis of pancreatic PKC isoforms during lactation and weaning showed a significant translocation of PKC-delta from the cytosol to the membrane fraction when compared with control animals. Translocation of PKC isoforms (alpha, delta and epsilon) in response to 12-O-tetradecanoyl phorbol 13-acetate (TPA) 1 microM (15 min, 37 degrees C) was comparable in pancreatic acini from control, lactating and weaning rats. In the control group, a significant translocation of all the isoforms (alpha, delta and epsilon) from the cytosol to the membrane was observed. The PKC isoform most translocated by TPA was PKC-delta. In contrast, no statistically significant increase in PKC-delta translocation was detected in pancreatic acini isolated from lactating or weaning rats. These results suggest that the PKC isoforms are already translocated to the surface of the acinar cells from lactating or weaning rats. In addition, they suggest that isoform specific spatial PKC distribution and translocation occur in association with the growth response previously described in the rat exocrine pancreas during lactation and weaning.

Animals↗
PubMed1982

Decreased bone mineral status in lactating adolescent mothers.

To determine the calcium and bone mineral status of lactating adolescents, we compared 12 lactating adolescents with 11 nonlactating adolescents, 11 lactating adults, and 11 nulliparous adolescent control subjects. At two and 16 weeks, there were no differences in maternal serum concentrations of calcium, phosphorus, alkaline phosphatase, or calcidiol (25-hydroxyvitamin D). The bone mineral content at two weeks among the four groups was not different, but at 16 weeks the lactating adolescents' bone mineral content was lower than that in the other groups. The lactating adolescents' bone mineral content was decreased between two and 16 weeks (1.049 +/- 0.088 vs 0.887 +/- 0.054 gm/cm; P less than 0.02). Dietary intakes were similar among the groups for calories, protein, vitamin D, calcium, and phosphorus. However, only three of ten lactating adolescents met the recommended dietary allowance for calcium or phosphorus (1,600 mg/day), whereas eight of ten nonlactating adolescents, six of seven lactating adults, and seven of ten adolescents control subjects met the recommended dietary allowance for calcium or phosphorus (P less than 0.05). Our data suggest that during 16 weeks of lactation, the adolescent mother may be at risk for bone demineralization because of low dietary intakes of calcium or phosphorus.

25-Hydroxyvitamin D 2↗
PubMed1994

Plasma lactate concentration as a predictor of death in neonates with severe hypoxemia requiring extracorporeal membrane oxygenation.

Plasma lactate concentrations have been used as an indicator of tissue hypoxia and as a predictor of the outcome of critical illness in adults. We evaluated the value of plasma lactate levels in predicting death in neonates with severe hypoxemia requiring extracorporeal membrane oxygenation (ECMO). We retrospectively reviewed the medical records in regard to plasma lactate levels and other clinical and biochemical measurements in 28 consecutive neonates requiring ECMO from July 1992 to December 1993. Seven infants died (mortality rate, 25%); 21 infants were short-term survivors and 20 infants were discharged from the unit. The plasma lactate values for survivors and nonsurvivors, respectively, were 10.0 +/- 6.35 mmol/L vs 24.9 +/- 9.90 mmol/L on admission, and 13.7 +/- 6.32 mmol/L vs 38.4 +/- 9.20 mmol/L at peak (both p < 0.00001). The survivors had a significant decrease in plasma lactate levels 12 hours after the start of ECMO: the nonsurvivors had persistent, severe hyperlactatemia. Apart from being less acidotic, the survivors did not differ from the nonsurvivors in other clinical and biochemical measurements. An admission plasma lactate concentration of < 25 mmol/L predicted survival with a sensitivity 100%, a specificity 71.4%, and positive and negative predictive values of 91.3% and 100%, respectively. We conclude that plasma lactate levels could be useful in predicting death in neonates with severe hypoxemia requiring ECMO. Further prospective evaluations of the predictive value of plasma lactate levels in sick neonates are required to confirm these initial observations.

Biomarkers↗
PubMed1999

Bone mineral changes during and after lactation.

OBJECTIVE: To investigate variations in bone mineral density during lactation and throughout the 12 months after scheduled cessation of lactation in relation to the resumption of ovarian function. METHODS: Three hundred eight mothers who decided to lactate were scheduled to fully breast-feed for 6 months, followed by a 1-month weaning period, and then suppress lactation with cabergoline. Their bone mineral density variations were compared with those of a control group of nonlactating mothers during the first 18 months postpartum. Half the lactating women were given daily oral calcium supplements of 1 g in an open design. RESULTS: There was a significant progressive decrease in bone mineral density in lactating women over the first 6 months, followed by recovery of bone mass up to levels that at 18 months were higher than baseline. In nonlactating women, bone mineral density increased progressively after delivery, and at 18 months postpartum had increased by 1.1-1.9% compared with baseline. Compared with lactating women who resumed menstruation within 5 months of delivery, breast-feeding mothers with longer amenorrhea initially lost more bone, but they also gained significantly more bone after resumption of menses, so there were no differences at 18 months postpartum. Oral calcium supplementation decreased bone loss, but had only a transient effect. CONCLUSION: A scheduled lactation period of 6 months, followed by a 1-month weaning period, allowed bone mineral density to reach higher values compared with early postpartum, regardless of calcium supplementation and duration of postpartum amenorrhea.

Adult↗
PubMed2003

Lactation and weaning effects on physiological and behavioral response to stressors.

Two experiments tested the effects of lactation and weaning on heart rate (HR), corticosterone, and behavioral responses to stress in Wistar rats. In Experiment 1, HRs in lactating, weaning, and control animals were recorded for 10-min periods before, during, and after immobilization stress. Compared with control animals, lactating and weaning animals showed a diminished initial HR response. In addition, HRs of weaning animals failed to habituate and showed a delayed decline after stress termination. In Experiment 2, behaviors, HRs, and corticosterone levels in the elevated plus maze (EPM) were compared among lactating, weaning, and control animals. Compared with control animals, weaning animals exhibited more anxiety behaviors. Contrary to expectation, compared to the other two groups, lactating animals exhibited more closed-arm entries, although they may have been motivated by maternal behavior, rather than anxiety. Initial HR responses to the plus maze were attenuated in lactating animals. Corticosterone levels after the plus maze were lowest in the lactating dams and highest in the control animals. The results from these two experiments are consistent with effects of breast-feeding and weaning observed in humans. In general, lactation is associated with an attenuated initial HR response to stress, while weaning is associated with exacerbated response to stressors.

Animals↗
PubMed2003

Evidence for involvement of neuropeptide Y and melanocortin systems in the hyperphagia of lactation in rats.

Hypothalamic neuropeptide Y (NPY) systems are upregulated during lactation in rats. Because NPY is central to the hypothalamic control of energy balance, the present studies tested the hypothesis that NPY contributes to the marked hyperphagia during lactation. A 4-day infusion of [D-tyr (27,36), D-thr (32)] NPY (27-36) (D-NPY(27-36)), a peptide analogue of NPY that antagonizes NPY-induced feeding, into the third ventricle at 1 microg/h transiently inhibited nocturnal feeding in nonlactating female rats. However, this antagonist had no effect on nocturnal feeding, but did transiently reduce food intake during the light hours, when infused into the third ventricle at the same dose in lactating females. An essentially similar pattern of results was obtained with chronic infusion into the third ventricle of the anorexigenic peptide alpha-melanocyte-stimulating hormone (alpha-MSH, 1 microg/h), in nonlactating and lactating rats. Both D-NPY(27-36) and alpha-MSH transiently reduced nocturnal food intake in lactating rats by approximately 10% when infused at the higher dose of 5 microg/h, and a marked inhibition of approximately 40% of both nocturnal and diurnal feeding was produced by a combined infusion of both at 5 microg/h. These results provide the first pharmacological evidence implicating specific neuromessengers in mediating the hyperphagia of lactation, and suggest that, while an action of NPY may contribute to the increased food intake seen in lactating animals, other systems are also involved. In particular, a reduction in melanocortin signaling during lactation may allow for an increased orexigenic influence of the agouti-related protein (AgRP), which is co-expressed with NPY.

Animals↗
PubMed1999

Reduced progesterone metabolites are not critical for plus-maze performance of lactating female rats.

Lactation has been associated with anxiolysis in several tests of anxiety. These observations, considered together with observations that progesterone and its 5alpha-reduced metabolites are anxiolytic in cycling, nonlactating females, raised the question of whether the changes in anxiety-related behaviors that accompany lactation are driven by reduced progesterone metabolites. Lactating female rats were tested on the plus-maze on postpartum days 2 or 7, and demonstrated enhanced open-arm performance relative to cycling, nonlactating females. Hormonal analysis indicated that while serum levels of both progesterone and its 3alpha,5alpha-reduced metabolite were increased in lactating females, the turnover of progesterone to the metabolite was markedly reduced during lactation. Furthermore, treatment with a 5alpha-reductase inhibitor for 3 days prior to testing potentiated the open-arm performance in lactating females, implying that enhanced open-arm performance was not mediated by the reduction of progesterone or other steroids. Additionally, analysis of GABA(A) receptor function indicated that parturition and lactation did not alter the sensitivity of the receptor to GABA or to modulation by reduced steroids. The mechanisms driving enhanced plus-maze behavior in lactating females appear to differ from mechanisms identified in nonlactating females.

5-alpha Reductase Inhibitors↗
PubMed1998

Comparison of the expression of two immediate early gene proteins, FosB and Fos in the rat preoptic area, hypothalamus and brainstem during pregnancy, parturition and lactation.

Medial preoptic area (MPA), supraoptic nucleus (SON), magnocellular (MaPVN) and parvocellular (PaPVN) paraventricular hypothalamic nuclei, and mesencephalic lateral tegmentum (MLT) are involved in maternal behavior, parturition and lactation. This study investigated the FosB and Fos immunoreactivity in these regions of virgin, pregnant, parturient, lactating, and lactating-arrested rats. The patterns of FosB and Fos expression were compared between the sections taken from the same animals. Quantitative immunohistochemistry revealed a significant increase in the numbers of FosB-positive neurons in the MPA, SON, MaPVN, and MLT of parturient and lactating females as compared with pregnant or virgin animals. In lactating rats, the numbers of FosB-positive neurons in the MPA, PaPVN, and MLT were increased, but the numbers in the SON and MaPVN were decreased as compared with parturient females. Many Fos-positive neurons were also seen in parturient and lactating rats, and the patterns of Fos expression in each region were quite similar to those of FosB. Moreover, double-labeling immunohistochemistry revealed that: (1) many FosB-positive nuclei were observed in oxytocin and vasopressin neurons of the SON and PVN in parturient rats; (2) within FosB-positive neurons, 89.5% in the MPA, 86.8% in the MLT of parturient rats, and 92% in the MPA and 90.8% in the MLT of lactating animals were also Fos-positive. Only a small number of FosB and Fos-positive neurons were seen in females that were killed in the early stage of parturition. Removal of the litters immediately after parturition completely eliminated FosB and Fos expression in each region in the dams. Taken together, the present results suggest that FosB expression is co-involved with Fos in the neural activation during parturition and lactation in rats.

Animals↗
PubMed1997

Mammary Stat5 abundance and activity are not altered with lactation state in cows.

Stat5 is a key intracellular mediator of prolactin signalling and can activate transcription of milk proteins in response to prolactin. Therefore, in animals such as mice where lactation is dependent on prolactin, Stat5 is likely to play an important role in establishing or maintaining lactation in the mammary gland. However, little is known about its role in lactation in the dairy cow. In order to address this, the levels of Stat5a and Stat5b protein, mRNA and Stat5 DNA-binding activity were measured in mammary tissue from mice and cows at different lactational states. In the cow, Stat5a and Stat5b protein and mRNA levels, as well as Stat5 DNA-binding activity were unaltered between pregnancy and established lactation. In contrast, in the mouse Stat5a and Stat5b protein, as well as Stat5 DNA-binding activity were clearly increased during lactation whereas Stat5a and Stat5b mRNA levels were highest during pregnancy as has been previously described. In both species only a minority of the epithelial cell nuclei were Stat5 positive during established lactation. These results suggest that there are significant differences in the biological role of Stat5 in controlling lactation between ruminants and rodents.

Animals↗
PubMed1999

Lactation-dependent down regulation of leptin production in mouse mammary gland.

Lactation-dependent regulation of leptin expression in mouse mammary gland and parametrial adipose tissue was estimated by RT-PCR analysis for virgin, pregnant, lactating and post-lactating mice, and the serum and milk leptin levels of these mice were also determined by ELISA. Leptin gene expression in mammary gland as well as in adipose tissue was obviously detected before pregnancy, markedly decreased to 30-50% after parturition and kept at the low level during lactation period, and restored to the original level after weaning. The leptin concentration of milk collected just before weaning was about two-fold higher than that of the milk collected at mid-lactating stages. The serum leptin levels of the mid- and late-lactating mice were not significantly higher than those of non-pregnant mice. These results suggested that the lactation-induced down regulation of leptin was associated with autocrine/paracrine action of leptin in mammary and adipose tissues, and that the milk leptin, especially at the latter stages of lactation, was not only ascribed to diffusive transport from maternal blood stream, but also regional production and secretion by mammary epithelial cells. This possible production of leptin by mammary epithelial cells was further supported by the fact that leptin was expressed by cultured cells of mammary epithelial cell line, COMMA-1D, in a manner negatively dependent on the lactogenic hormones.

Adipose Tissue↗
PubMed1997

The concentrations of some gut polypeptides are elevated during lactation in ruminants.

Circulating concentrations of both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1(7-36)amide (GLP-1) were determined in dry and lactating sheep. Both polypeptides were significantly higher in lactating animals compared with dry. The half-life of both in plasma was determined by intravenous injection of GIP or GLP-1 in both dry and lactating animals, but neither peptide showed a significantly different value during lactation. Thus, the increased circulating concentrations during lactation must result from increased secretion, probably resulting from the increased feed intake during lactation. Serum insulin concentrations were significantly lower during lactation, which poses the question of how lactating animals maintain lower circulating insulin levels in the presence of higher levels of insulinotropic agents.

Animals↗
PubMed2001

Effects of a four-day hyperinsulinemic-euglycemic clamp in early and mid-lactation dairy cows on plasma concentrations of metabolites, hormones, and binding proteins.

The effects of insulin, using a 4 d hyperinsulinemic-euglycemic clamp, on plasma concentrations of hormone, metabolites, and binding proteins were evaluated in four Holstein dairy cows during wk 4 and 17 of lactation. Insulin was infused at 1 microg/kg/hr for 96 hr during the clamp period. Compared with the pre-clamp period, plasma insulin concentrations increased 7-fold and 4-fold during the clamp periods in early and mid-lactation, respectively. The total amount of glucose infused was higher (P < 0.05) during the clamp in early lactation. The clamp decreased plasma concentrations of non-esterified fatty acids (P < 0.001) during early lactation while differences in mid-lactation were minor. The clamp also decreased plasma concentration of beta-hydroxybutyrate (P < 0.001), plasma urea nitrogen (P < 0.001), and true protein (P < 0.01) although the patterns of decline differed between early and mid-lactation. Growth hormone (GH) concentrations decreased (P < 0.001) and insulin-like growth factor-1 (IGF-1) increased (P < 0.01) during the clamp period suggesting a direct effect of insulin on the un-coupling of the GH/IGF-1 axis. Levels of IGF binding protein-2 (IGFBP-2) decreased (P < 0.01) during the clamp period. The relative proportion of IGFBP-2 decreased (P < 0.001) and that of IGFBP-3 increased (P < 0.001) during the clamp period. There were no interactions between the clamp period and stage of lactation on GH, IGF-1, or IGFBPs. Overall, most plasma variables measured were affected in the same way during the two clamps, but the pattern of change often varied with stage of lactation.

3-Hydroxybutyric Acid↗
PubMed2002

Respiratory responses to intravenous infusion of sodium lactate in male and female Wistar rats.

In patients with panic disorder or premenstrual dysphoria, anxiety attacks can be triggered by intravenous administration of sodium lactate. Since respiratory symptoms, such as hyperventilation and shortness of breath, are characteristic features of spontaneous as well as lactate-induced panic, an involvement of central or peripheral chemoreceptors in this reaction has been suggested. In the present study, we examined to what extent intravenous infusion of sodium lactate influences respiratory parameters in freely moving male and female Wistar rats. Prompted by clinical reports suggesting that the susceptibility to spontaneous and lactate-induced anxiety may be influenced by the menstrual cycle, we also investigated if the effect of lactate on respiration in female rats is estrus cycle-dependent. Male and ovariectomized female rats exposed to sodium lactate displayed a larger increase in respiratory rate than rats given an infusion of saline. In intact female rats, the response to lactate infusion was significantly more pronounced in the diestrus phase than in the proestrus/estrus phase of the cycle. It is concluded that sodium lactate is a respiratory stimulant in rat, and that this effect is influenced by female sex steroids.

Analysis of Variance↗
PubMed2000

Glucose metabolism in crossbred Holstein cattle feeding on two types of roughage at different stages of lactation.

An experiment was performed to study the glucose kinetics of crossbred Holstein cattle feeding on either hay or 5% urea-treated rice straw during early lactation (30 days post partum), mid-lactation (120 days post partum) and late lactation (210 days post partum). Two breeds: Holstein FriesianxRed Sindhi (50:50 = 50% HF) and Holstein FriesianxRed Sindhi (87.5:12.5 = 87.5% HF) were used. In early lactating 87.5% HF animals feeding on either hay or urea-treated rice straw, the high milk yields and lactose secretion were related to glucose uptake by the udder and udder blood flow as compared with those of 50% HF animals. Marked decreases in udder blood flow, glucose uptake, lactose secretion and milk yield were apparent in mid- and late lactation of both groups of 87.5% HF animals. In contrast, both groups of 50% HF animals showed no significant changes in udder blood flow, udder glucose uptake, lactose secretion and milk yields throughout the course of lactation. Total glucose entry rate using 3-[3H] glucose infusion, recycling of glucose carbon and plasma glucose clearance significantly increased during late lactation for 50 and 87.5% HF animals feeding on urea-treated rice straw. The utilization rates of glucose using [U-(14)C] glucose infusion were not significantly different among groups of animals and periods of lactation. It can be concluded that 87.5% HF animals have the genetic potential for a higher milk yield, but a shorter peak yield and poorer persistence in comparison with 50% HF animals. Changes in the utilization of glucose by the mammary gland for milk production in both groups of crossbred animals during feeding on either hay or urea-treated rice straw would be dependent on intramammary changes.

Animal Feed↗
PubMed1982

Effects of fasting during mid pregnancy or early lactation on mammary development and milk yield in mice.

Mice were fasted during pregnancy or early lactation and the effects on mammary development and milk yield studied on d 13 and d 18 of pregnancy and on d 7 of lactation. Fasting during pregnancy reduced body weight and mammary weight on d 13 of pregnancy but not on d 18. Mammary concentrations and total contents of DNA and RNA ([DNA], [RNA], DNAt, RNAt) were increased or unchanged on d 13 but significantly decreased on d 18. Fasting had no effect on fetal number or weight at either stage of pregnancy. Fasting on d 1 of lactation reduced mammary weight, DNAt and RNAt (but not [DNA] or [RNA]) and the incorporation of tritiated thymidine into DNA or d 2 of lactation. Mammary gland weight and composition on d 7 of lactation were not significantly affected by fasting for 24 h on d 1 of lactation or for 40 h on d 11-13 of pregnancy, except that DNAt was decreased slightly by the latter treatment. Milk yield (litter weight gain) was depressed markedly during fasting on d 1 of lactation, but thereafter recovered so that it was the same as controls between d 3 and 13 of lactation; after d 13 it fell once more. A 40 h fast on d 11-13 of pregnancy had no effect on milk yield. Thus, although normal mammary development was inhibited by starvation, the gland was subsequently able to compensate so that milk yield was not reduced.

Animals↗