Interruption Of Lactation Research Articles

Peripartum Cardiomyopathy. Medical Support Strategy

Peripartum cardiomyopathy (PPCM) is an idiopathic myocardial insufficiency that occurs in the absence of any diagnosed heart disease during the last month of pregnancy or during the first 5 months after delivery.
 The aim. To improve immediate and long-term maternal outcomes in patients with PPCM by establishing an optimal strategy for its diagnosis, treatment, delivery and medical support during the postpartum period.
 Materials and methods. The article presents the experience of multidisciplinary medical care for 11 pregnant wo-men and postpartum women with dilated cardiomyopathy (DCM) on the basis of the National Amosov Institute of Cardio-vascular Surgery and the Institute of Pediatrics, Obstetrics and Gynecology named after acad. O. M. Lukianova of NAMS of Ukraine. After the differential diagnosis, 8 women were defined as patients with PPCM, and 3 women had family history of the disease (DCM in relatives). All the patients were examined according to the protocol using the history, examination, and instrumental and laboratory findings.
 Results. After in-hospital treatment there was an increase in the left ventricular ejection fraction (LVEF) in the group of patients with PPCM from 28.3 ± 9.3% to 37.6 ± 7.6% and a decrease in end-diastolic volume (EDV) from 196.7 ± 47.7 ml to 181.3 ± 59.7 ml, end-systolic volume (ESV) from 104.25 ± 33.3 ml to 94.2 ± 35.1 ml. In four cases, patients with severe left ventricular (LV) dysfunction underwent urgent preterm Cesarean section in the second trimester of pregnancy. There were no early maternal losses, there were two perinatal losses of extremely premature infants (16 and 27 weeks of gesta-tion). In the follow-up period (23.5 ± 11.6 months), LVEF further increased up to 42.9 ± 8.4% and EDV and ESV decreased up to 170.1 ± 49.5 and 82.7 ± 40.6 ml, respectively. In 7 (87.5%) patients with PPCM, a significant improvement in clini-cal condition and pumping function of the heart was registered at the time of discharge from the hospital, and there was further improvement in the indicators for another 12 months, but complete recovery of cardiac function was achieved only in 3 (37.5%) patients. In patients from the group of family type DCM, complete recovery of LV myocardial function was not observed in any of the 3 studied cases.
 The article discusses the timing of the occurrence and diagnosis of PPCM, the main clinical, instrumental and labora-tory signs of the pathology, methods of cardiological, cardiosurgical and obstetric support of such pregnant women.
 Conclusions. The terms of the onset of PPCM manifestations may be wider (earlier) according to our observations and should be the subject of further research. The strategy of medical care for pregnant women doesn’t particularly depend on the type of DCM. However, obstetric tactics aimed at early delivery of a patient with PPCM with severe myocardial insufficiency are feasible in combination with interruption of lactation and in most cases allow to achieve compensation of circulation and partial recovery of LV function. Prescription of bromocriptine for this purpose seems appropriate. The use of repeated courses of levosimendan in patients with PPCM is feasible and helps to improve the LV function in the early postpartum period.

Use of pyridoxine hydrochloride in the interruption of lactation in female dogs with pseudopregnancy.

The aim of this research was to evaluate the use of pyridoxine hydrochloride and its associated side effects in the treatment of pseudopregnancy in female dogs. A total of 40 female dogs, with no defined breed, in non-gestational diestrus, with clinical complaint of milk production were selected. The female dogs were divided into four experimental groups of 10 animals each, treated orally for 20 days with 10mg/kg/day (G1) and 50mg/kg/day (G2) of pyridoxine hydrochloride (vitamin B6), 5μg/kg/day of cabergoline (G3), and with a placebo, in the case of the control group (G4). The effects of the treatments on milk production were investigated, as well as possible systemic side effects, macroscopic uterine and ovarian alterations, and uterine histology. During the investigated period, G2 and G3 were equally efficient (P>0.05) in lactation suppression, differing (P>0.05) from the other groups. There were no systemic side effects or uterine changes associated with administration of the studied drug. Vitamin B6 (50mg/kg) has shown to be a safe and economically viable alternative for lactation interruption in female dogs with pseudopregnancy.

Mucosal Immunity and Liver Metabolism in the Complex Condition of Lactation Insufficiency.

Lactation insufficiency is variously defined and includes the inability to produce milk, not producing enough milk to exclusively meet infant growth requirements, and pathological interruption of lactation (e.g., mastitis). Of women with intent-to-breastfeed, lactation insufficiency has been estimated to affect 38%-44% of newly postpartum women, likely contributing to the nearly 60% of infants that are not breastfed according to the World Health Organization's guidelines. To date, research and clinical practice aimed at improving feeding outcomes have focused on hospital lactation support and education, with laudable results. However, researchers' reports of recent rodent studies concerning fundamental lactation biology have suggested that the underlying pathologies of lactation insufficiency may be more nuanced than is currently appreciated. In this article, we identify mucosal biology of the breast and lactation-specific liver biology as two under-researched aspects of lactation physiology. Specifically, we argue that further scientific inquiry into reproductive state-dependent regulation of immunity in the human breast will reveal insights into novel immune based requirements for healthy lactation. Additionally, our synthesis of the literature supports the hypothesis that the liver is an essential player in lactation-highlighting the potential that pathologies of the liver may also be associated with lactation insufficiency. More research into these biologic underpinnings of lactation is anticipated to provide new avenues to understand and treat lactation insufficiency.

Early weaning modulates eating behavior and promotes hypofunction of the serotonergic (5HT) system in juvenile male rats.

Early life stress (ELS) has been associated with developmental impairments. Early weaning (EW)is a postnatal stress model consisting of interruption of lactation and maternal care. The 5HT-system has been associated with neurobehavioral modulations promoted by ELS. Thus, the present work aims to investigate the effects of early weaning on feeding behavior and serotonergic system of juvenile male rats. For this, rats were submitted to early (PND15) or natural (PND30) weaning and had the body weight, food intake in circadian phases, and food intake in response to fenfluramine assessed. mRNA expression of serotoninergic receptors (5HT1A and 5HT2C) and transporter (SERT) was assessed in the hypothalamus and brainstem, as well as NPY and POMC mRNA expression in hypothalamus. The results show that early weaning promoted changes in the percentage of weight gain during lactation period and increase in body weight at PND40. It was also observed that EW promoted increase and decrease in food intake in light and dark phase, respectively, and leads to a decreased action of fenfluramine on inhibition of food intake. In addition, early weaning promoted increased NPY and SERT mRNA expression in the hypothalamus and 5HT2C in the brainstem. Together, the data indicate that the stress caused by early weaning impairs the eating behavior of juvenile male rats through hypofunction of the 5HT-system.

FACTORS OF INFLUENCE ON THE MORBIDITY BY MASTITIS OF COWS

Diseases of mastitis of dairy livestock cause significant economic losses, exceeding losses from all non-communicable diseases combined. It leads to a sharp decline in milk production or interruption of lactation, premature culling of milking premature culling of dairy herd, large material costs. In addition, the problem of mastitis is of social importance, because when eating milk containing pathogenic microorganisms or their toxins, people, especially children, also have serious illnesses.
 The aim of the research is to determine the factors affecting the level of cow damage with mastitis.
 The research was conducted in 2014–2016 on dairy farms in Donetsk region. Average milk yield per cow per year in the farms was at the level of 4000–5055 kg of milk. Before the beginning of the experiment, a structural analysis of the dairy herds was carried out on the farms, taking into account the age of the cows, the physiological state, the stage of lactation, productivity and pedigree composition.
 Diagnosis of subclinical mastitis in milk cows was carried out by mastidinovoy breakdown on control plates. The dependence of the number of hidden mastitis on such indicators as milk yield, lactation stage, elements of technology of keeping, age of animals and season of the year was taken into account.
 Research methods: experimental, supplemented by analytical studies, measurements, calculations and observations.
 It is showed that the structure of the herd of enterpriceses AgroPromservice, Bogoyavlinske, VostokAgro and Rossiya is approximately. It was found that with two-time milking their number was 20.5%, for two-time milking with milking it was 23.9%, and with three-time milking a day it was 17.6%.
 Influence of disinfection of the nipples of the mammary gland after milking with the drug "De Laval" "Dipal-concentrate" showed that with a double treatment the incidence of mastitis was 26.4%; When disinfectiont of the nipples of the breast after milking once a day, this indicator increases by 5.3%.
 Analysis of the disinfection of the teat with iodine and glycerin after each milking showed that the incidence of mammary gland hidden mastitis is reduced from 39.3% to 30.8%, that is, 8.5%.
 It was revealed that the incidence in the summer and winter periods ranged from 14.6 to 23.9%, in the spring and autumn periods from 19.5 to 36.9%.
 Studies have shown that the number of mammary gland diseases depends on the age of the animals, in particular, in primiparous animals it was less than in older cows.
 The most resistant to the disease are low-productive animals with a productivity of 3000 kg of milk and less for lactation (the number of diseases was 2.6–9.0%). With the increase in milk productivity from 4000–5500 kg of milk and more the number of diseases increases to 13.9–50.8%.
 Analysis of the presence of subclinical mastitis in farms, depending on the lactation stage of cows, indicates that the greatest number of hidden mastitis occurs in the second or fourth months of lactation, at 10–11 months of lactation and significantly decreases in the middle of lactation.
 Thus, the factors influencing the level of cow damage with mastitis were determined: milk productivity, lactation stage, milking and maintenance technology, animal age and season of year. The most influential factors are the productivity of animals and the technology of milking and keeping animals.

Factors influencing the recruitment of lactating women in a clinical trial involving direct oral anticoagulants: a qualitative study

Background Robust human data on medication use during lactation is scarce. With increasing medication use in postpartum women, it is important to conduct clinical lactation studies measuring the excretion of drugs in human milk and generate evidence. We plan to conduct a clinical lactation study, involving the direct oral anticoagulants (DOACs). Objective This study aimed to identify factors influencing lactating women’s clinical trial participation and to improve the design of a proposed DOACs clinical lactation study. Setting Lactating women in London, UK. Methods Three focus groups were conducted in lactating women with differing experiences of being prescribed anticoagulants during puerperium. Main outcome measures Thematic framework approach was used to analyse and identify key themes, using NVivo version 11. Results Eight breastfeeding mothers participated. Women’s decision-making on clinical trial participation was largely influenced by the lactation stage and previous breastfeeding experience. The concern of harm to their infant caused by the test medication or interruption of lactation were the predominant barriers to potential participation. Around 6 months following the birth of their infant and second-time mothers appeared to be more amenable to clinical trial participation. The provision of home visits for the execution of the study was highly recommended. Conclusion Our findings suggest that lactating women would participate in a clinical trial during the breastfeeding period, if the timing is right and if the woman is an experienced mother. Home visits will be provided in our proposed DOACs clinical lactation study.

ACOG Committee Opinion No. 756: Optimizing Support for Breastfeeding as Part of Obstetric Practice.

As reproductive health experts and advocates for women's health who work in conjunction with other obstetric and pediatric health care providers, obstetrician-gynecologists are uniquely positioned to enable women to achieve their infant feeding goals. Maternity care policies and practices that support breastfeeding are improving nationally; however, more work is needed to ensure all women receive optimal breastfeeding support during prenatal care, during their maternity stay, and after the birth occurs. Enabling women to breastfeed is a public health priority because, on a population level, interruption of lactation is associated with adverse health outcomes for the woman and her child, including higher maternal risks of breast cancer, ovarian cancer, diabetes, hypertension, and heart disease, and greater infant risks of infectious disease, sudden infant death syndrome, and metabolic disease. Contraindications to breastfeeding are few. Most medications and vaccinations are safe for use during breastfeeding, with few exceptions. Breastfeeding confers medical, economic, societal, and environmental advantages; however, each woman is uniquely qualified to make an informed decision surrounding infant feeding. Obstetrician-gynecologists and other obstetric care providers should discuss the medical and nonmedical benefits of breastfeeding with women and families. Because lactation is an integral part of reproductive physiology, all obstetrician-gynecologists and other obstetric care providers should develop and maintain skills in anticipatory guidance, support for normal breastfeeding physiology, and management of common complications of lactation. Obstetrician-gynecologists and other obstetric care providers should support women and encourage policies that enable women to integrate breastfeeding into their daily lives and in the workplace. This Committee Opinion has been revised to include additional guidance for obstetrician-gynecologists and other obstetric care providers to better enable women in unique circumstances to achieve their breastfeeding goals.

ACOG Committee Opinion No. 756 Summary: Optimizing Support for Breastfeeding as Part of Obstetric Practice.

As reproductive health experts and advocates for women's health who work in conjunction with other obstetric and pediatric health care providers, obstetrician-gynecologists are uniquely positioned to enable women to achieve their infant feeding goals. Maternity care policies and practices that support breastfeeding are improving nationally; however, more work is needed to ensure all women receive optimal breastfeeding support during prenatal care, during their maternity stay, and after the birth occurs. Enabling women to breastfeed is a public health priority because, on a population level, interruption of lactation is associated with adverse health outcomes for the woman and her child, including higher maternal risks of breast cancer, ovarian cancer, diabetes, hypertension, and heart disease, and greater infant risks of infectious disease, sudden infant death syndrome, and metabolic disease. Contraindications to breastfeeding are few. Most medications and vaccinations are safe for use during breastfeeding, with few exceptions. Breastfeeding confers medical, economic, societal, and environmental advantages; however, each woman is uniquely qualified to make an informed decision surrounding infant feeding. Obstetrician-gynecologists and other obstetric care providers should discuss the medical and nonmedical benefits of breastfeeding with women and families. Because lactation is an integral part of reproductive physiology, all obstetrician-gynecologists and other obstetric care providers should develop and maintain skills in anticipatory guidance, support for normal breastfeeding physiology, and management of common complications of lactation. Obstetrician-gynecologists and other obstetric care providers should support women and encourage policies that enable women to integrate breastfeeding into their daily lives and in the workplace. This Committee Opinion has been revised to include additional guidance for obstetrician-gynecologists and other obstetric care providers to better enable women in unique circumstances to achieve their breastfeeding goals.

EFFECTS OF FLOUR OR FLAXSEED OIL UPON INTRA-ABDOMINAL ADIPOSITY IN MALE RATS SUBJECTED TO EARLY WEANING

The present study was designed to evaluate intra-abdominal adiposity in rats subjected to early weaning and subsequently treated with diet containing flour or flaxseed oil until young life. Pups were weaned for separation from mothers at 14 days (early weaning, EW), and 21 days (control, C). After 21 days, control (C60) was fed with control diet. EW was divided into control (EWC60); flaxseed flour (EWFF60); flaxseed oil (EWFO60) diets until 60 days. At 21-60 day, intra-abdominal fat mass were evaluated. At 60 days, retroperitoneal adipocyte area was determined. At 21 days, EW group displayed lower (P<0.05) intra-abdominal fat mass. At 60 days, EWC60 group displayed lower (P<0.05) intra-abdominal fat mass. Adipocytes area were lower (P<0.05) in experimental groups. EWC60 displayed lower (P < 0.05) adipocytes area (vs. EWFF60 and EWFO60). Flour and flaxseed oil diets contribute to recovery of intra-abdominal adiposity after precocious interruption of lactation.

The Difficulties in Antihypertensive Drug Prescription During Lactation: Is the Information Consistent?

The lack of consistent official information on the use of medications during lactation is probably one of the main reasons leading to an excess of prudence, based on presumption of risk rather than on evidence. The objective of this study was to compare the level of agreement between different official sources available to doctors and women on the use of medications during lactation. Sources of information included governmental regulatory agencies (RAs) and scientific sources (SS). The package leaflets (PLs) and summaries of product characteristics (SPCs) were retrieved from online databases of the European Union and U.S. RAs. Among the SS, the latest edition of the book Medications and Mothers' Milk by Hale and Rowe and the LactMed database were selected. Information about the use of 11 antihypertensive medications during breastfeeding was analyzed. The PLs and SPCs report a higher risk profile than the one expressed by SS, and they often suggest the interruption of lactation even for compatible medications. Health professionals should be supported by official, accurate, comprehensive, and consistent information about maternally ingested medication and breastfeeding management to facilitate proper decision-making.

Brain development in male rats subjected to early weaning and treated with diet containing flour or flaxseed oil after 21 days until 60 days.

The precocious interruption of lactation is a prime factor for developmental plasticity. Here we analyzed whether flour or flaxseed oil treatment contributes to body and brain mass in male rats subjected to early weaning. Pups were weaned for separation from their mother at 14 (early weaning, EW) and 21 days (control, C). At 21 days, some of the pups were evaluated (C21 v. EW21). After 21 days, control pups (C60) were fed a control diet. EW pups were divided into those fed a control diet (EWC60), those given flaxseed flour (EWFF60), and those given flaxseed oil (EWFO60) until 60 days. EW21 showed lower body and absolute brain mass and higher relative brain mass. At 60 days, EWC60 and EWFO60 had lower body mass. With regard to relative brain mass, EWC60 was heavier; EWFO60 had lower values compared with EWC60 and higher values compared with C60 and EWFF60. These results indicated that flaxseed flour, in comparison with flaxseed oil, contributes to brain development after EW.

Effect of lactation on maternal postpartum cardiac function and adiposity: a murine model

Lactation is associated with reduction in maternal metabolic disease and hypertension later in life; however, findings in humans may be confounded by socioeconomic factors. We sought to determine the independent contribution of lactation on cardiovascular parameters and adiposity in a murine model. Following delivery, CD-1 female mice were randomly divided into 2 groups: lactated (L; nursed pups for 3 weeks, n = 10), and nonlactated (NL; pups were removed after birth, n = 12). Blood pressure (BP) was assessed prepregnancy and at 1 and 2 months' postpartum. Visceral and subcutaneous adipose tissue determined by computed tomography and left ventricular ejection fraction, cardiac output, and the E/A ratio determined by microultrasound were evaluated at 1 and 2 months' postpartum. The results were analyzed using a Student t test (significance at P < .05). We observed a significantly different maternal BP at 2 months' postpartum with relatively greater BP in NL (systolic BP: NL, 122.2 ± 7.2 vs L, 96.8 ± 9.8 mm Hg; P = .04; diastolic BP: NL, 87.0 ± 6.8 vs L, 65.9 ± 6.2 mm Hg; P = .04). Visceral adipose tissue was significantly increased in NL mice at 1 (22.0 ± 4.1% vs 10.7 ± 1.8%, P = .04) and 2 months' postpartum (22.9 ± 3.5% vs 11.2 ± 2.2%, P = .02), whereas subcutaneous adipose tissue did not differ between the groups. At 2 months' postpartum, ejection fraction (51.8 ± 1.5% vs 60.5 ± 3.8%; P = .04), cardiac output (14.2 ± 1.0 vs 18.0 ± 1.3 mL/min; P = .02) and mitral valve E/A ratio (1.38 ± 0.06 vs 1.82 ± 0.13; P = .04) were significantly lower in NL mice than L mice. Our data provide evidence that interruption of lactation adversely affects postpartum maternal cardiovascular function and adiposity.

Growth of Exclusively Breastfed and Self-Weaned Children of Greece Aged 0–36 Months

Breastfeeding is recognized as an important public health issue with substantial social and economic implications. Moreover, the growth of exclusively breastfed babies differs from that of their formula-fed counterparts. The purpose of this study was to evaluate the physical growth of exclusively breastfed and self-weaned boys and girls of Greece 0-36 months of age. The physical growth of children was monitored from birth up to 36 months of age. Body weight, length/height, and head circumference were recorded. The study population included 101 boys and 105 girls who were recruited consecutively from a private breastfeeding clinic in the second largest city of Greece and through La Leche League groups throughout the country during 2000 to 2005. All infants were exclusively breastfed for ≥ 6 months. Anthro software ( www.who.int/childgrowth/software/en/index.html ) was used to compare the data of our study population and the World Health Organization standards for weight, length/height, and head circumference for age. Male and female infants at 12 months had almost tripled their weight (192% and 190% increase, respectively) and had increased their length (height) by 48% and 47%, respectively, and head circumference had increased by 35% and 33%, respectively. In both sexes the relative length/height and the head circumference-for-age increase rates were higher from the first to the second month of life than at any other period. Long-term exclusively breastfed infants grow normally. Hence, no recommendations for the interruption of lactation and/or supplementation with formula are justified.

Early weaning is associated with higher neuropeptide Y (NPY) and lower cocaine- and amphetamine-regulated transcript (CART) expressions in the paraventricular nucleus (PVN) in adulthood

The interruption of lactation for a short period, without the use of pharmacological substances or maternal separation, causes offspring malnutrition and hypoleptinaemia and programmes for metabolic disorders such as higher body weight and adiposity, hyperphagia, hyperleptinaemia and central leptin resistance in adulthood. Here, in order to clarify the mechanisms underlying the phenotype observed in adult early-weaned (EW) rats, we studied the expression of neuropeptide Y (NPY), agouti-related peptide (AgRP), pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) in different hypothalamic nuclei by immunohistochemistry and Western blot. In the EW group, the teats of lactating rats were blocked with a bandage to interrupt lactation during the last 3d, while control pups had free access to milk throughout the entire lactation period. At age 180d, EW offspring showed higher NPY staining in the paraventricular nucleus (PVN), as well as NPY protein content (+68%) in total hypothalamus than control ones. AgRP showed no changes in staining or Western blot. POMC content was not affected; however, its distribution pattern was altered. CART-positive cells of EW offspring had lower immunoreactivity associated with reduced cell number in the PVN and lower protein content (-38%) in total hypothalamus. The present data indicate that precocious weaning can imprint the neuronal circuitry, especially in the PVN, and cause a long-term effect on the expression of specific orexigenic and anorexigenic neuropeptides, such as NPY and CART, that can be caused by leptin resistance and are coherent with the hyperphagia observed in these animals.

Paucity of CD4 + CCR5 + T Cells May Prevent Transmission of Simian Immunodeficiency Virus in Natural Nonhuman Primate Hosts by Breast-Feeding

Simian immunodeficiency virus (SIV) persistence in wild populations of African nonhuman primates (NHPs) may occur through horizontal and vertical transmission. However, the mechanism(s) and timing of the latter type of transmission have not been investigated to date. Here we present the first study of SIV transmissibility by breast-feeding in an African NHP host. Six mandrill dames were infected with plasma containing 300 50% tissue culture infective doses of SIVmnd-1 on the day after delivery. All female mandrills became infected, as demonstrated by both plasma viral loads (VLs) and anti-SIVmnd-1 seroconversion. Neither fever nor lymphadenopathy was observed. At the peak of SIVmnd-1 viral replication (days 7 to 10 postinoculation), plasma VLs were high (8 x 10(6) to 8 x 10(8) RNA copies/ml) and paralleled the high VLs in milk (4.7 x 10(4) to 5.6 x 10(5) RNA/ml). However, at the end of the breast-feeding period, after 6 months of follow-up, no sign of infection was observed for the offspring. Later on, during a 4-year follow-up examination, two of the offspring showed virological evidence of SIVmnd-1 infection. Both animals seroconverted at least 6 months after the interruption of lactation. In conclusion, despite extensive viral replication in mandrill mothers and high levels of free virus in milk, no SIVmnd-1 transmission was detectable at the time of breast-feeding or during the following months. Since we observed a markedly lower expression of CCR5 on the CD4(+) T cells of young mandrills and African green monkeys than on those of adults, we propose that low levels of this viral coreceptor on CD4(+) T cells may be involved in the lack of breast-feeding transmission in natural hosts of SIVs.

Reversible transdifferentiation of secretory epithelial cells into adipocytes in the mammary gland

Mammalian breast adipose tissue is replaced by a milk-secreting gland during pregnancy; the reverse process takes place upon interruption of lactation. Morphological and bromodeoxyuridine studies provide indirect evidence that mouse mammary adipocytes transform into secretory epithelial cells during pregnancy and revert to adipocytes after lactation. By using the Cre-loxP recombination system we show that the mammary gland of whey acidic protein (WAP)-Cre/R26R mice, in which secretory epithelial cells express the lacZ gene during pregnancy, contains labeled adipocytes during involution. Conversely, adipocyte P2-Cre/R26R mice, in which adipocytes are labeled before pregnancy, contain labeled secretory epithelial cells during pregnancy. We conclude that reversible adipocyte-to-epithelium and epithelium-to-adipocyte transdifferentiation occurs in the mammary gland of adult mice during pregnancy and lactation.

Sexual dimorphism of apoptosis in lactotrophs induced by bromocryptine.

Interruption of lactation provokes a massive degeneration of surplus lactotrophs in the rat pituitary gland. This process was determined to be non-apoptotic in nature, and this observation raised many questions as cell death by apoptosis has been described in several tissues after withdrawal of trophic hormones. In this study we explored various experimental conditions and gathered new information leading to a comprehensive interpretation of the factors involved in the induction of apoptosis in lactotrophs. With this aim, we investigated the apoptogenic role of bromocryptine on lactotrophs in several experimental models involving male and female rats. Even though bromocryptine increased the expression of P53 in all experimental models, apoptosis was only triggered in male and ovariectomised females. In both conditions the oestrogen stimulation is low or nil, and the occurrence of apoptosis can be correlated with the appearance of atypical lactotrophs and the level of P53 expression. The existence of apoptosis was validated with the observation of DNA laddering in electrophoresis. By contrast, in intact females the majority of lactotrophs present signs of an increased prolactin secretion and no DNA fragmentation was found. Endogenous oestrogens probably prevent the deep inhibitory effect of a dopamine agonist and thus block apoptosis. Besides, the morphological analysis of regressing pituitary revealed the coexistence of lactotrophs to be an important factor responsible for tissue remodelling in functional pituitary glands undergoing apoptotic and non-apoptotic cell deaths. The non-apoptotic cell death appeared to be an important factor responsible for tissue remodelling in functional pituitary glands. The present results suggest that the occurrence of apoptosis in regressing lactotrophs caused by bromocryptine is sexually dimorphic and probably associated with the survival effect of endogenous oestrogens in intact females.

Apoptotic and non-apoptotic cell death in hormone-dependent glands.

The proliferation of cells and cell death are involved in the maintenance of appropriate tissue homeostasis. In the present study, two different mechanisms of cell death were identified in the prostate and pituitary glands when morphological data, fragmentation of DNA, and TUNEL labelling of apoptotic nuclei were compared. Typical cell death by apoptosis was identified by morphological and molecular approaches in the prostate after orchidectomy. By contrast, neither DNA fragmentation nor TUNEL labelling were found in dead cells occurring in the pituitary gland after interruption of lactation. Regressing lactotrophs were characterised by condensation and disruption of the cytoplasmic matrix, but preserved intact nuclei until advanced stages of regression. Degenerating "dark" cells comparable to those described in the pituitary were also seen coexisting with typical apoptosis in the prostate epithelial lining of orchidectomised rats. Both forms of cell death could be clearly differentiated, because dark cells suffer severe alterations of cytoplasmic organelles while maintaining the integrity of the nucleus. In contrast, apoptotic cells present well-preserved cytoplasmic organelles, but grossly disrupted nuclei with fragmentation and condensation of chromatin.

An alternative pathway for clearance of dead lactotropes from rat pituitary gland

In the pituitary glands of lactating rats there is a striking proliferation of lactotropes during pregnancy and lactation. After the cessation of lactation, the population of lactotropes experiences an extensive programmed cell death of redundant cells until it reaches prepregnancy levels. The regressive changes occurring in lactotropes are autolytic in nature and usually these cells are engulfed by stellate cells. Other involuting lactotropes are mobilized toward the blood capillaries and some go into the capillary lumen for final disposal, presumably in the mononuclear phagocyte system. In this study we report a sequence of events occurring in regressing lactotropes, investigated by a systematic electron microscope analysis of the rat pituitary gland at different periods after interruption of lactation. Direct disposal of degenerating lactotropes and their cell remnants appears to be an alternative pathway for the clearance of the regressing cells that occur extensively among surplus lactotropes following ablactation.

当院で経験した妊娠後骨粗しょう症の１例

Post-pregnancy osteoporosis, which was reported for the first time by Nordin in 1955 originates from back pain and vertebral compression fracture during pregnancy or delivery. This disease is so rare that only a few reports are available in the literature. According to these reports, subjects as young as 20-30 years at the onset are predominant and about 80% of them develop the osteoporosis following their first experience of pregnancy. There is a strong correlation with lactation, which is, however, not always responsible for the present disease. The disease is self-limiting, and interruption of lactation and conservative treatment lead to remission within several months with a favorable prognosis.Recently, we experienced a 32-year-old woman who developed back pain 2 months after delivery of her second child and had a lumbar compression fracture, which, however, was relieved by conservative treatment. We would like to report the present case with particular emphasis on the change in bone mineral density, as measured using Dual energy X-ray Absorptiometry and a review of the relevant literature.