The protective effect of berberine against lipopolysaccharide-induced abortion by modulation of inflammatory/immune responses.

OBJECTIVE: Berberine is an isoquinoline derivative alkaloid with anti-inflammatory activity. In this study, we investigated the protective effects of berberine in prevention of LPS-induced abortion. MATERIALS AND METHODS: On the gestation day (GD) 9.5, the pregnant mice were injected with low, medium, and high doses of berberine or with PBS. After 4 h, berberine or PBS-pretreated mice were injected with LPS. On GD 11.5, blood samples and uterine tissues were collected from treated mice and percentage of abortion and serum levels of NO, TNF-α, IL-10, and IL12p70 were measured by macroscopic examination and sandwich ELISA, respectively. RESULTS: Our findings show that mice injected with berberine were resistant to LPS-induced abortion. We also found that this treatment prevents the reduction of IL-10 and the enhancement of NO, TNF-α, and IL-12p70 in LPS-treated pregnant mice. CONCLUSIONS: Taken together, our results suggest that berberine as an anti-inflammatory agent has protective effects on LPS-induced abortion by modulation of inflammatory/immune responses.

Isolation of Salmonella typhi from high vaginal swab in a case of septic abortion.

Salmonella Typhi can be a significant cause of morbidity and mortality in pregnant females with adverse outcomes. Risk of infections increases manifold during pregnancy due to hormonal changes and immunological phenomena. S. Typhi has the ability to cross placenta (vertical transmission) resulting in miscarriage, stillbirth or premature labour. We report a case of a pregnant female who was admitted to emergency department with fever, missed abortion and hypovolaemic shock. Subsequently, S. Typhi was isolated from her high vaginal swab and blood cultures. Follow-up cultures were negative for S. Typhi, and the patient was discharged after 10 days. The possibility of salmonellosis should be considered if a pregnant woman residing in an endemic area presents with high-grade fever. Furthermore, it should be promptly treated to prevent foetal loss.

CCR5 Is Involved in Interruption of Pregnancy in Mice Infected with Toxoplasma gondii during Early Pregnancy.

Toxoplasmosis can cause abortion in pregnant humans and other animals; however, the mechanism of abortion remains unknown. C-C chemokine receptor type 5 (CCR5) is essential for host defense against Toxoplasma gondii infection. To investigate the relationship between CCR5 and abortion in toxoplasmosis, we inoculated wild-type and CCR5-deficient (CCR5-/-) mice with T. gondii tachyzoites intraperitoneally on day 3 of pregnancy (embryonic day 3 [E3]). The pregnancy rate decreased as pregnancy progressed in infected wild-type mice. Histopathologically, no inflammatory lesions were observed in the fetoplacental tissues. Although wild-type mice showed a higher parasite burden at the implantation sites than did CCR5-/- mice at E6 (3 days postinfection [dpi]), T. gondii antigen was detected only in the uterine tissue and not in the fetoplacental tissues. At E8 (5 dpi), the embryos in infected wild-type mice showed poor development compared with those of infected CCR5-/- mice, and apoptosis was observed in poorly developed embryos. Compared to uninfected mice, infected wild-type mice showed increased CCR5 expression at the implantation site at E6 and E8. Furthermore, analyses of mRNA expression in the uterus of nonpregnant and pregnant mice suggested that a lack of the CCR5 gene and the downregulation of tumor necrosis factor alpha (TNF-α) and CCL3 expression at E6 (3 dpi) are important factors for the maintenance of pregnancy following T. gondii infection. These results suggested that CCR5 signaling is involved in embryo loss in T. gondii infection during early pregnancy and that apoptosis is associated with embryo loss rather than direct damage to the fetoplacental tissues.

Cohort study of the incidence of spontaneous preterm birth and septic abortion referred by pathological examination in Gifu prefecture in Japan.

AIMS: To clarify the incidence of spontaneous preterm birth (PB) and septic abortion (sab) in Gifu prefecture in Japan. STUDY DESIGN: This prospective, population-based cohort study was approved by our hospital's Institutional Review Board. All 36 hospitals (100%) in Gifu prefecture offering obstetrical services participated in the study. Patient enrollment criteria were: sab and PB from 22 to <37weeks gestation (WG), excluding for maternal and fetal indications. Pathological examinations before 36 WG and associated factors for both PB and chorioamnionitis (CAM) stage 3 were analyzed by multiple logistic regression analysis judging from minimum daily clinical information in Gifu prefecture. RESULTS: The sab rate per all deliveries was 29/16871 (0.17%) at 16.9±2.9 WG. The total spontaneous PB rate was 615/16871 (3.65%) at 34.5±2.7 WG, with birth weight (BW) 2267±557g. There were 26 (0.15%) PBs from 22+0 to 27+6 WG (weeks+days) at 25.2±1.5 WG, with BW 745±199g. Among 214 pathological examinations, CAM was detected in 80% (sab) and 63% (PB<36 WG), respectively. Funisitis were 14% and 17% respectively. Episodes of serial genital bleeding and/or hematoma at <12 WG were more frequent in sab and earlier PB (<28 WG) associated with CAM stage 3 (odds 1.9, P<0.0001). Combined factors such as bleeding and past history of CAM correlated with earlier delivery at 23.4±5.9 WG (P=0.0032). CONCLUSION: In Gifu prefecture, the incidence of sab was 0.17% (per all deliveries) and 3.65% of spontaneous PB. The combined risk of past CAM history and bleeding was associated with earlier delivery among total preterm birth.

Experimental challenge of pregnant cattle with the putative abortifacient Waddlia chondrophila.

Waddlia chondrophila is a Gram-negative intracellular bacterial organism that is related to classical chlamydial species and has been implicated as a cause of abortion in cattle. Despite an increasing number of observational studies linking W. chondrophila infection to cattle abortion, little direct experimental evidence exists. Given this paucity of direct evidence the current study was carried out to investigate whether experimental challenge of pregnant cattle with W. chondrophila would result in infection and abortion. Nine pregnant Friesian-Holstein heifers received 2 × 108 inclusion forming units (IFU) W. chondrophila intravenously on day 105-110 of pregnancy, while four negative-control animals underwent mock challenge. Only one of the challenged animals showed pathogen-associated lesions, with the organism being detected in the diseased placenta. Importantly, the organism was re-isolated and its identity confirmed by whole genome sequencing, confirming Koch's third and fourth postulates. However, while infection of the placenta was observed, the experimental challenge in this study did not confirm the abortifacient potential of the organism.

Insights into potential pathogenesis mechanisms associated with Campylobacter jejuni-induced abortion in ewes.

BACKGROUND: Campylobacter jejuni is commonly found in the gastrointestinal tract of many food-animals including sheep without causing visible clinical symptoms of disease. However, C. jejuni has been implicated in ovine abortion cases worldwide. Specifically, in the USA, the C. jejuni sheep abortion (SA) clone has been increasingly associated with sheep abortion. In vivo studies in sheep (the natural host) are needed to better characterize the virulence potential and pathogenesis of this clone. RESULTS: Pregnant ewes intravenously (IV) or orally inoculated with ovine or bovine abortion-associated C. jejuni SA clones exhibited partial or complete uterine prolapse with retained placenta, and abortion or stillbirth, whereas delivery of healthy lambs occurred in pregnant ewes inoculated with C. jejuni 81-176 or in the uninfected group. In sheep inoculated with the SA clone, histopathological lesions including suppurative necrotizing placentitis and/or endometritis coincided with: 1) increased apoptotic death of trophoblasts, 2) increased expression of the host genes (e.g. genes encoding interleukin IL-6 and IL-15) related to cellular necrosis and pro-inflammatory responses in uterus, and 3) decreased expression of the genes encoding GATA binding protein 6, chordin, and insulin-like 3 (INSL3) that account for embryonic development in uterus. Immunohistochemistry revealed localization of bacterial antigens in trophoblasts lining the chorioallantoic membrane of ewes inoculated with the C. jejuni SA clone. CONCLUSIONS: The results showed that C. jejuni SA clones are capable of causing abortion or stillbirth in experimentally infected sheep. Furthermore, down- or up-regulation of specific genes in the uterus of infected pregnant ewes might implicate host genes in facilitating the disease progression. Since the C. jejuni SA strains share genotypic similarities with clones that have been isolated from human clinical cases of gastroenteritis, these strains might represent a potential public health risk.

Disseminated cryptococcosis in an HIV-negative pregnancy: a case of cryptococcal septic abortion complicating an immunocompetent pregnancy.

Cryptococcus neoformans, a well-known pathogen of the immunocompromised host, is rarely reported as a cause of disseminated infection in the immunocompetent pregnant woman. Reported herein is the case of a young gravid woman, who initially presented with vague systemic symptoms that evolved into a disseminated cryptococcosis, which was resistant to standard parenteral antifungal therapy and resulted in abortion. Experience from this case suggests that cryptococcal infection should be considered in the differential diagnosis of pregnant women presenting with vague systemic symptoms such as fever, abdominal pain, and generalized lymphadenopathy.

Utero-adnexal damage in septic abortion. Histopathological study on 91 cases.

Septic abortion represents the main causes of abortion-induced maternal death. Hysterectomy may represent a beneficial therapeutic solution for septic abortion, nevertheless with irreversible effects on a woman's reproductive condition. The study analyzes the anatomopathological damage found in ninety-one patients hospitalized for septic abortion. The patients were admitted to the "Dr. D. Popescu" Clinical Hospital, Timisoara, between 1980-1989 and 1999-2008; hysterectomy was performed in all the cases to eliminate uterine sepsis responsible for the emerging complications.

[Spontaneus abortion caused by Listeria monocytogenes--report of three cases]. / Listeria monocytogenes jako prícina spontánního abortu--popis trí prípadu.

This paper describes three cases of spontaneous abortion caused by Listeria monocytogenes which were diagnosed during the outbreak of listeriosis in late 2006. Both clinical and morphological features were highly consistent. The abortion between 19 and 20 weeks of gestation was preceded by high maternal fever. The fetal disease was miliary widespread with involvement of adrenals, liver and lungs in particular. There was always present a pustular rash. Histological examination of the placentas revealed acute chorioamnionitis with massive growth of gram-positive rods in the amnion in all cases. Acute villitis and intervillous microabscesses were additionally noted in one case. The diagnosis in all reported cases was not established until fetal autopsy. The final diagnosis was confirmed by microbiological examination using samples submitted during the autopsy examination.

A 'minimum dose' of lipopolysaccharide required for implantation failure: assessment of its effect on the maternal reproductive organs and interleukin-1alpha expression in the mouse.

Genital tract infections caused by gram-negative bacteria induce abortion and are one of the most common complications of human pregnancy. This study was carried out to decipher the mechanism of gram-negative bacterial lipopolysaccharide (LPS)-induced pregnancy loss, using a mouse (Park strain) model. Since many of the biological effects of LPS are mediated by interleukin (IL)-1alpha, the role of IL-1alpha in LPS-induced pregnancy loss was studied. Pregnant female animals were injected intra-peritoneally (i.p.) with different doses (1 to 50 microg) of LPS from Salmonella minnesota Re-595, on day 0.5 of pregnancy. We found that 250 microg/kg body weight (i.e. 5 microg/female mouse) of LPS when given on day 0.5 of pregnancy was the 'minimum dose' (MD) required to completely inhibit the implantation of the blastocyst in the mouse. The effect of this dose on the pathophysiology of the various reproductive organs (i.e. uterus, ectoplacental cones, developing fetus, ovaries etc.) was assessed on day 14 of pregnancy. The effects of this dose on the level and pattern of expression of the proinflammatory cytokine IL-1alpha in the maternal uterine horns and preimplantation stage embryos were studied by RT-PCR. A single dose (100 ng/mouse) of recombinant mouse IL-1alpha was given i.p. to pregnant females on day 1 of pregnancy to study its effect on implantation. Our results show that treatment of the pregnant animals with LPS may alter cell proliferation and induce leukocyte infiltration, degeneration of luminal glandular epithelium, and hyperplasia in the various reproductive organs, and may also alter both embryonic and uterine IL-1alpha expression. IL-1alpha administration also caused implantation failure similar to that of LPS. The observations suggest that the determined MD of LPS may alter the expression of developmentally important proinflammatory cytokines such as IL-1alpha, which could, in turn, inhibit the normal processes of blastocyst implantation. Therefore, it is proposed that the LPS-induced histopathological alterations in the various reproductive organs of pregnant animals could be mediated by IL-1alpha and this may be one of the causes of failure of blastocyst implantation in the mouse.

Clostridium welchii infection following amniocentesis: a case report and review of the literature.

We report a case of severe Clostridium welchii infection following amniocentesis with septicaemia, haemolysis, DIC, pulmonary oedema and renal failure. Full recovery occurred following aggressive conservative management using antibiotics, endometrial curettage and intensive monitoring. The patient retained her uterus and had a successful pregnancy two years later although caesarean section for uterine rupture was required. Conservative management with conservation of the uterus and ovaries may be a safe and effective option in the management of severe Clostridium infections, using antibiotics, endometrial curettage and multidisciplinary team input.

Aborto séptico, Hospital "Dr. Adolfo Prince Lara" 1985-1996 / Septic abortion Hospital \"Dr. Adolfo Prince Lara\" 1985-1996

Conocer la incidencia del aborto séptico y características de la embarazada por la íntima dependencia entre los factores sépticos y morbimortalidad materna. Hospital "Dr. Adolfo Prince Lara", Puerto Cabello, Estado Carabobo, Venezuela. Estudio retrospectivo, descriptivo de 10157 abortos de los cuales 427 fueron sépticos en el período 1985-1996. El aborto tuvo una incidencia global de 16,17 por ciento; el aborto séptico 4,2 por ciento con rangos de 12,37 por ciento (1988) y 1,85 por ciento (1994), hay tendencia a cifras menores en los últimos 5 años. Predominaron pacientes residentes en barrios (56,67 por ciento), concubinas (67,45 por ciento), menores de 30 años (68,86 por ciento), con gestaciones entre II-V (63,7 por ciento), edad gestacional menor de 13 semanas (57,61 por ciento), antecedentes de maniobra abortiva (1,87 por ciento). El diagnóstico fue principalmente por clínica y laboratorio (69,09 por ciento), grado séptico I (92,51 por ciento), tratadas con antibióticos y curetaje (75,37 por ciento), Hospitalizadas de dos a tres días (57,85 por ciento), la mayor morbilidad fue anemia (5,85 por ciento). Hubo dos muertes maternas (1989-1990). Uno de cuatro abortos fue séptico revelándose factores sociales. Todo obliga a programas de apoyo y orientación familiar, adecuada atención médica para evitar secuelas de morbimortalidad materna

[Septic abortion in Campylobacter jejuni infection]. / Septischer Abort bei Campylobacter-jejuni-Infektion.

Case report of a 24 year old woman II G/I P with enterocolitis and septicaemia caused by Campylobacter jejuni (C.) in the following time abortion at 16 weeks of gestation. Diagnostics, therapy, review of literature.

A retrospective study of bovine abortions associated with Bacillus licheniformis.

A retrospective study of bovine abortions associated with Bacillus licheniformis is described. The material consisted of 2445 bovine abortions submitted for diagnostics from 1986 through 1993. Initially, B. licheniformis had been isolated from 81 cases. Sections of these cases were re-examined microscopically and immunohistochemically by a PAP technique using a primary antibody against B. licheniformis. Of these abortions, 47 were most likely associated with B. licheniformis as tissue lesions with immunostained bacteria were present in these. In the remaining cases the diagnosis may not have been established due to the lack of sufficient materials, or the isolation of the bacterium was considered to be a result of contamination. In four cases concomitant infections with B. licheniformis and bovine virus diarrhoea virus were present. Abortions caused by B. licheniformis were predominantly seen during the winter months and in late pregnancy. The most common lesions were necrotizing placentitis followed by fetal multifocal suppurative bronchopneumonia. Immunohistochemically, B. licheniformis was demonstrated in association with tissue lesions and intracellularly in trophoblasts. The pattern of bacterial isolations, especially from the placenta, lungs, and abomasal contents, combined with the histological findings points to B. licheniformis abortions as being of haematogenous origin with subsequent transplacental spread to the fetus.

[Septic cervical pregnancy. A case report]. / Embarazo séptico cervical. Informe de un caso.

One clinical case of cervical pregnancy studied at the General Hospital of Acapulco, Guerrero, México, is presented clinically it was manifested as septic abortion and diagnosed by ultrasonography. In the past 12 years of establishment, 30,000 deliveries have been recorded and during this period, only four well documented cases were found and two of the previously reported by one us. Only two cervical pregnancy presenting as abortion, a relationship not emphasized in literature, was made in 1975.

Fiebre tifoidea durante la gestación: curso clínico, tratamiento y repercusión perinatal / Typhoid fever guring gestion: clinical sourse, treatment an perinatal repercussion

La prevalencia de fiebre tifoidea (FT) en nuestro país es alta, afectando principalmente a niños y adultos jóvenes. El número de informes en la literatura acerca de la asociación de FT y embarazo son escasos, no obstante, la mayoría de autores coinciden que la gestación no modifica la presentación clínica ni las alteraciones de laboratorio de las pacientes con FT. Por otra parte, se ha demostrado que la FT influye desfavorablemente en el curso del embarazo, asociándose a abortos y a partos pretémino. En el presente artículo se informa cinco casos de pacientes embarazadas complicadas con FT; una de ellas abortó, una presentó un parto pretérmino con la muerte neonatal de su producto y las tres restantes tuvieron un curso normal del embarazo, sin anormalidades en sus recién nacidos. La morbi-mortalidad tanto martena como fetal se encuentra en estrecha relación al tratamiento adecuado de esta infección. Durante la gestación está contraindicado el uso de cloranfenicol, pero tanto la ampicilina como ceftriaxona son opciones terapéuticas adecuadas para el tratamiento de la FT en esta etapa

Fetal listeriosis during the second trimester of gestation.

Listeriosis is common and is implicated in about 3% of second-term abortions examined in our laboratory. Maternal fever was followed rapidly in all instances by the expulsion of a nonmacerated fetus. Chorioamnionitis was always present and was associated with placental microabscesses. Leukocytic infiltrates were frequent in fetal tissues, being present in adrenal, lung, and skin. Listeria monocytogenes was isolated from 8 of the 205 abortions that had microbiological cultures (3.9%). The clinical features and morphological lesions were so characteristic that the diagnosis of listeriosis could be made in 5 of the 217 fixed abortuses received during the same period, but without culture. In contrast to the third trimester of pregnancy, there were no inflammatory lesions in the central nervous system in our small series.