Intact Mycobacterium leprae Isolated from Placenta of a Pregnant Woman, China.

Whether Mycobacterium leprae transmits from placenta to fetus remains unknown. We describe the case of a pregnant woman with untreated histoid leproma. Although her newborn was healthy, laboratory examination revealed intact M. leprae present in the placenta, suggesting that the placental barrier might prevent vertical dissemination of M. leprae.

Leptin and its Receptors in Human Placenta of Small, Adequate, and Large for Gestational Age Newborns.

Alterations in birth weight impact postnatal outcome and adult metabolic health. Therefore, fetal growth regulation is crucial for preventing chronic metabolic diseases. Leptin has been suggested to play an important role in placental and fetal growth, albeit its specific mechanisms of action have not been elucidated. The aim of this study was to analyze leptin concentrations in placenta, cord blood, and maternal blood of SGA, AGA, and LGA (small, adequate and large for gestational age, respectively) newborns, as well as placental leptin receptor (LEPRa and LEPRb) protein expression. We performed a cross-sectional comparative study in 3 groups of healthy mothers and their term newborns at delivery (SGA, AGA, and LGA, n=20 per group). Placental, maternal blood, and cord blood leptin content were measured by ELISA. Placental LEPRa and LEPRb protein expression were determined by Western Blot. Maternal leptin concentrations correlated positively with maternal weight before and at the end of gestation, without differences between groups. Cord leptin is higher in LGA and lower in SGA, whereas placental leptin is higher in SGA. Placental leptin was inversely correlated with placental weight, independently from maternal weight and gestational age. Both LEPRa and LEPRb expression are lower in SGA, while LEPRa positively correlated with placental weight and birthweight. The current findings indicate that placental leptin and its receptors are differentially expressed in SGA, AGA, and LGA newborns. We suggest that placental leptin and LEPR protein expression may influence placental growth and thus, birth weight.

Reduced Perinatal Leptin Availability May Contribute to Adverse Metabolic Programming in a Rat Model of Uteroplacental Insufficiency.

Leptin availability in perinatal life critically affects metabolic programming. We tested the hypothesis that uteroplacental insufficiency and intrauterine stress affect perinatal leptin availability in rat offspring. Pregnant rats underwent bilateral uterine vessel ligation (LIG; n = 14), sham operation (SOP; n = 12), or no operation (controls, n = 14). Fetal livers (n = 180), placentas (n = 180), and maternal blood were obtained 4 hours (gestational day [E] 19), 24 hours (E20), and 72 hours (E22) after surgery. In the offspring, we took blood samples on E22 (n = 44), postnatal day (P) 1 (n = 29), P2 (n = 16), P7 (n = 30), and P12 (n = 30). Circulating leptin (ELISA) was significantly reduced in LIG (E22, P1, P2) and SOP offspring (E22). Postnatal leptin surge was delayed in LIG but was accelerated in SOP offspring. Placental leptin gene expression (quantitative RT-PCR) was reduced in LIG (E19, E20, E22) and SOP (E20, E22). Hepatic leptin receptor (Lepr-a, mediating leptin degradation) gene expression was increased in LIG fetuses (E20, E22) only. Surprisingly, hypoxia-inducible factors (Hif; Western blot) were unaltered in placentas and were reduced in the livers of LIG (Hif1a, E20; Hif2a, E19, E22) and SOP (Hif2a, E19) fetuses. Gene expression of prolyl hydroxylase 3, a factor expressed under hypoxic conditions contributing to Hif degradation, was increased in livers of LIG (E19, E20, E22) and SOP (E19) fetuses and in placentas of LIG and SOP (E19). In summary, reduced placental leptin production, increased fetal leptin degradation, and persistent perinatal hypoleptinemia are present in intrauterine growth restriction offspring, especially after uteroplacental insufficiency, and may contribute to perinatal programming of leptin resistance and adiposity in later life.

[Global lessons of Minamata disease--a man's worth].

Minamata disease (MD) was first recognized in May 1956. Its first recognized victims were 3 and 5 years old children. Environmental contamination most rapidly and seriously affected the physiologically and socially weak among the residents. Methylmercury (MeHg) had accumulated in fishes and shellfishes and those who ate them had been poisoning with it. MD is an indirect poisoning by MeHg through the food chain as a result of environmental contamination, and is the first known disease to cause abnormalities in the fetus due to a toxic substances passing through the placenta. In 1962 MeHg poisoning through the placenta was found for the first time in the world. It used to be considered that poisoning was caused by direct exposure to a toxic substance, and that toxic substances did not pass the placenta. MD had implications in various fields. Namely it also stirred up legal, ethical, and eugenic arguments concerning fetal protection. Also man thought about a man's worth.

Adipocytokine expression in placentas from pre-eclamptic and chronic hypertensive patients.

OBJECTIVE: Growing evidence suggests that concentration of the adipocytokines leptin and adiponectin may be affected by risk of hypertension during pregnancy. Leptin and leptin receptor gene expression has been studied in placentas obtained from pre-eclamptic patients, but not in those with chronic high blood pressure (CHBP). Adiponectin receptors remain unstudied in placentas obtained from hypertensive patients. METHODS: Therefore, we investigated relative mRNA expression of selected adipocytokine genes (leptin, leptin receptors (LEPRA, LEPRB, LEPRC, LEPRD) and adiponectin receptors (ADIPOR1, ADIPOR2)) in placental tissues from women with pre-eclampsia (n = 6) or CHBP (n = 8). Placentas from 28 normotensive patients were analyzed as controls. mRNA extracted from biopsies taken from the maternal and fetal sides of the placenta was investigated using real-time polymerase chain reaction. RESULTS: Compared with controls, significant increases in leptin mRNA expression were seen in placentas from pre-eclamptic patients on the maternal (p = 0.01) and fetal (p = 0.02) sides, and in placentas from CHBP mothers on the fetal side (p = 0.001). Maternal-side tissue from CHBP patients was not significantly different from that of controls (p = 0.08), but this might be due to the small sample size. No significant differences were seen in mRNA expression for most of the adipocytokine receptors tested for hypertensive cases compared with controls. However, there was a decrease in LEPRC (pre-eclamptic, maternal side, p = 0.03) and LEPRD (pre-eclamptic, maternal side, p = 0.01; CHBP, fetal side, p = 0.009) in case-control analysis. CONCLUSIONS: This pilot study shows that increases seen in leptin expression in placentas from hypertensive mothers might be a consequence of defects in placentation associated with this disease, and motivates further region-specific adipocytokine gene expression analysis across this organ.

Arf and RhoA regulate both the cytosolic and the membrane-bound phospholipase D from human placenta.

In this paper we demonstrate for the first time that human placenta contains a cytosolic phospholipase D (PLD) activity. This activity had a pH optimum of 7.0 and was stimulated by PIP2 and inhibited by oleate. Furthermore, cytosolic PLD was stimulated by 30 microM GTP gamma S (6-14-fold) and by the small G proteins 1 microM mArf3 (2-fold) and 0.37 nM RhoA (2-fold). This is the first report to show RhoA activation of a cytosolic PLD. The activation by mArf3 was maintained after partial purification on DEAE Sepharose of the enzyme. We have previously reported the existence of a membrane-bound PLD from human placenta, which is stimulated by PIP2, but not by oleate (Vinggaard, A. M. & Hansen, H. S. (1995) Biochim. Biophys. Acta 1258, 169-176). Here we show that oleic acid and alpha-linolenic acid both dose-dependently inhibited solubilized membrane PLD (65% inhibition at 4 mM), whereas stearic acid (4 mM) had no effect. Thus, the presence of double bonds in the fatty acid is important for the inhibitory effect. Furthermore, placental membrane PLD was activated by 30 microM GTP gamma S (4-fold) and by mArf3 (1 microM) and RhoA (0.37 nM) by a factor of 3 and 2, respectively. The solubilized membrane phospholipase D was partially purified to a basal specific activity of 25-37 nmol/min/mg. This preparation was devoid of endogenous RhoA and Arf and could not be stimulated by GTP gamma S. However, mArf3 (1 microM) still activated this partially purified membrane PLD, whereas RhoA (0.37 nM) was not able to activate this PLD fraction. In conclusion, our results suggest that the human placenta contains a PLD that is located both in the cytosol and the membranes, and that is activated by PIP2, mArf3 and RhoA but inhibited by oleate.

[Initial manifestation of tuberculoid leprosy in pregnancy. Guidelines for diagnosis and therapy]. / Erstmanifestation einer tuberkuloiden Lepra in der Schwangerschaft. Leitlinien zur Diagnostik und Therapie.

Pregnancy has long been associated with the first presentation of clinical leprosy or aggravation of the existing disease. In Germany leprosy has been diagnosed in 107 patients since 1980. A 27-year-old Singhalese female, gravida 2 at 14 weeks' gestation was admitted with well defined, elevated, erythematous lesions on her cheeks and nose. Clinical examination revealed central anaesthesia in the lesions. No further signs of leprosy in the skin, the mucosae and the peripheral nerves were found. Fite-Faraco staining of the skin biopsy showed sporadic acid-fast bacilli and confirmed an active subpolar tuberculoid leprosy (TTs). Outpatient treatment was immediately initiated with oral rifampin 600 mg monthly and dapsone 100 mg daily. During the 4-month treatment cycle the skin lesions vanished completely. Additional leprosy reactions did not occur and the medication was well tolerated. However, in the 32nd gestational week the patient was readmitted with premature labour and 3 weeks later Caesarean section was performed because of cardiotocographic pathology. Polymerase chain reaction (PCR) for M. leprae of placental tissue was negative. Antibodies against phenolic glycolipid 1 (PGL 1) of M. leprae (IgM-Elisa and Dot-Elisa) from cord blood, maternal and newborn blood were not found. On the fifth postpartal day the healthy mother and her baby were discharged. In conclusion, leprosy in pregnancy can be treated safely and successfully by combined drug therapy.

Estudo da placenta na hanseníase / Study of placenta in leprosy

Foram estudadas 15 placentas procedentes de três grupos de grávidas. Sete eram de hansenianas, acompanhadas durante toda a gestação e o parto realizou-se no Hospital Universitário Antonio Pedro...O estudo imunohistoquímico do afluxo inflamatório, nas vilosites da Doença de Hansen, foi semelhante ao detectado nas de outras etiologias. O achado do agente etiológico assume papel relevante, a vasculite foi caracterizada por endotélio huperplasiado, edema endotelial, sub endotelial, da camada média média e adventícia. As alterações foram generalizadas e semelhantes, no setor arterial e venoso, houve predomínio do achado da Mycobacterium leprae nas formas bacilíferas e a visualização das bactérias foi facilitada pela técnica utilizada, os níveis de anticorpos IgM anti PGL1 foram elevados em gestantes bacilíferas. Não houve correlação entre os níveis de anticorpos maternos e dos seus respectivos recém-nascidos.

Lepromatous placentitis and intrauterine fetal infection in lepromatous nine-banded armadillos (Dasypus novemcinctus).

Three pregnant lepromatous armadillos along with the three sets of four fetuses and their placentae were studied histopathologically. Mycobacterium leprae were present in the decidual tissue, trophoblastic cells which line the chorionic villi, and in the cells that form the internal structure of the villi. Acid-fast organisms were also seen in the spleens of three fetuses. Congenital infection is clearly possible in leprosy in the armadillo and may also occur in humans.

The placenta in leprosy.

Eighty-one placentae from women with leprosy and 17 placentae from healthy controls were subjected to a detailed macroscopic, light microscopic, ultrastructural, immunopathological, microbiological and biochemical study. The placental morphology and immunohistology were normal, and there was no morphological evidence of infection of the placenta due to M. leprae. No acid-fast bacilli or acid-fast bacillary granules were seen on light microscopy of any of the placentae from leprous women, although homogenates from two out of seven placentae from women with very active lepromatous leprosy contained acid-fast bacilli in very small numbers. The small placental size of women with leprosy, most marked in those with lepromatous leprosy, appears to be due to a decrease in placental cell size, rather than to a reduced number of cells in the placenta. It is postulated that the small placenta and reduced fetal birth weight observed in lepromatous leprosy are a consequence of depressed maternal immune reactivity.

Estrogen excretion in pregnant women with leprosy: evidence of diminished fetoplacental function.

Estrogen excretion was assayed in 64 women with leprosy and 15 healthy control women. The mean estrogen excretion was lower in women with leprosy than in controls and the incidence of subnormal estrogen values was higher in the leprosy patients than in the controls. There was an association between infant birth weight and frequency of subnormal estrogen excretion. These features were most marked in women with lepromatous leprosy and are further evidence of diminished fetoplacental function in women with leprosy.

Babies of mothers with leprosy have small placentae, low birth weights and grow slowly.

One hundred and sixteen women with leprosy and 31 healthy controls were studied throughout 155 pregnancies, and their babies were observed for a period of up to two years. Babies of mothers with leprosy weighed less than those of healthy mothers; the placental weights and coefficients followed the same trend. The babies of the mothers with leprosy grew more slowly than those of the healthy mothers and these findings were most marked in the babies of mothers with lepromatous leprosy. The cause of the reduced feto-placental weight is thought to be related to the immune status of the mother.

Cultivation of the Douglas strain of Mycobacterium lepraemurium in continuous culture.

Cultivation of Mycobacterium lepraemurium in cell-free media has not yet been successful, perhaps because of deterioration of the nutritional quality of the medium with prolonged incubation at 37 degrees C. Trials with a continuous culture technique, involving regular change of a simple liquid medium prepared from human placenta, demonstrated active fission of the Myco. lepraemurium cells. Abundant growth in the form by macroscopically visible colonies has not been achieved even after prolonged incubation up to 8 months.