Complications in pregnant women with autoimmune diseases

BACKGROUND: Autoimmune diseases complicate pregnancy in several manners. This study aimed at describing the most common complications in pregnant women with autoimmune diseases. METHODS: This was a descriptive and retrospective study. Two groups of pregnant women with autoimmune diseases were included: 1) Those who since the beginning of gestation received obstetrical care at a tertiary-level hospital and 2) Women who were treated first in a medical unit not specialized in rheumatological diseases. Odds ratio, logistic regression and multinomial logistic regression were used to determine risk of complicated pregnancy. RESULTS: The distribution of autoimmune diseases in our sample is as follows: systemic lupus erythematosus (SLE): 6, rheumatoid arthritis (RA): 4, primary anti-phospholipid syndrome (APS): 4, systemic sclerosis (SS): 2, mixed connective tissue disease (MCTD): 1. Eight patients were seen throughout their gestation at a tertiary-level hospital and nine were referred from other non-specialized hospitals. Patients in the first group had four complications, and those of the second group, 28. The Odds Ratio (OR) of having a complication in the hospitals of reference compared to the "Mónica Pretelini Sáenz" Maternal-Perinatal Hospital (HMPMPS) was of 29.8 (95% CI: 1.29-692.46; Z statistic 2.11, p = 0.03). In relation to the logistic regression, this test was not significant neither for the group nor the treatment scheme for the presence of at least one complication. The multinomial logistic regression did not show significant predictive probabilities of the different possible outcomes for the group and drug treatment scheme. CONCLUSION: Pregnant women with autoimmune diseases can have an OR up to 29.8 to develop complications when they are not cared for by specialized personnel

Risk assessment of Soulatrolide and Mammea (A/BA+A/BB) coumarins from Calophyllum brasiliense by a toxicogenomic and toxicological approach.

Calophyllum brasiliense (Calophyllaceae) is a tropical rain forest tree distributed in Central and South America. It is an important source of tetracyclic dipyrano coumarins (Soulatrolide) and Mammea type coumarins. Soulatrolide is a potent inhibitor of HIV-1 reverse transcriptase and displays activity against Mycobacterium tuberculosis. Meanwhile, Mammea A/BA and A/BB, pure or as a mixture, are highly active against several human leukemia cell lines, Trypanosoma cruzi and Leishmania amazonensis. Nevertheless, there are few studies evaluating their safety profile. In the present work we performed toxicogenomic and toxicological analysis for both type of compounds. Soulatrolide, and the Mammea A/BA + A/BB mixture (2.1) were slightly toxic accordingly to Lorke assay classification (DL50 > 3000 mg/kg). After a short-term administration (100 mg/kg/daily, orally, 1 week) liver toxicogenomic analysis revealed 46 up and 72 downregulated genes for Mammea coumarins, and 665 up and 1077 downregulated genes for Soulatrolide. Gene enrichment analysis identified transcripts involved in drug metabolism for both compounds. In addition, network analysis through protein-protein interactions, tissue evaluation by TUNEL assay, and histological examination revealed no tissue damage on liver, kidney and spleen after treatments. Our results indicate that both type of coumarins displayed a safety profile, supporting their use in further preclinical studies to determine its therapeutic potential.

Toxicogenomic analysis of pharmacological active coumarins isolated from Calophyllum brasiliense.

Calophyllum brasiliense (Calophyllaceae) is a tropical rain forest tree, mainly distributed in South and Central America. It is an important source of bioactive natural products like, for instance soulatrolide, and mammea type coumarins. Soulatrolide is a tetracyclic dipyranocoumarins and a potent inhibitor of HIV-1 reverse transcriptase and Mycobacterium tuberculosis. Mammea A/BA and A/BB coumarins, pure or as a mixture, are highly active against several leukemia cell lines, Trypanosoma cruzi and Leishmania amazonensis. In the present work, a toxicogenomic analysis of Soulatrolide and Mammea A/BA + A/BB (3:1) mixture was performed in order to validate the toxicological potential of this type of compounds. Soulatrolide or mixture of mammea A/BA + A/BB (3:1) was administered orally to male mice (CD-1) at dose of 100 mg/kg/daily, for 1 week. After this time, mice were sacrificed, and RNA extracted from the liver of treated animals. Transcriptomic analysis was performed using Affymetrix Mouse Gene 1.0 ST Array. Robust microarray analysis (RMA) and two way ANOVA test revealed for mammea mixture treatment 46 genes upregulated and 72 downregulated genes; meanwhile, for soulatrolide 665 were upregulated and 1077 downregulated genes. Enrichment analysis for such genes revealed that in both type of treatments genetic expression were mainly involved in drug metabolism. Overall results indicate a safety profile. The microarray data complies with MIAME guidelines and are deposited in GEO under accession number GSE72755.

Trends in the chemical and pharmacological research on the tropical trees Calophyllum brasiliense and Calophyllum inophyllum, a global context.

Tropical trees of Calophyllum genus (Calophyllaceae) have chemical and biological importance as potential source of secondary active metabolites which can lead to the development of new drugs. Research on this species has been rising since 1992 due to the discovering of anti-HIV properties of Calanolide A found in Calophyllum inophyllum leaves. This compound is the most important natural product for potential development of new anti-HIV drugs and phytomedicines. The scientometric analysis (1953-2014) here performed revealed that the most studied species of Calophyllum genus are: C. inophyllum and C. brasiliense, distributed in the Asian, and American continents, respectively. Current research on these species is carried out mainly in India and Brazil, respectively, where these species grow. Research on C. brasiliense is focused mainly on ecological, antiparasitic, cytotoxic properties, and isolation of new compounds. Chemical studies and biodiesel development are the main topics in the case of C. inophyllum. Text mining analysis revealed that coumarins, and xanthones are the main secondary active metabolites responsible for most of the reported pharmacological properties, and are potential compounds for the treatment of leukemia and against intracellular parasites causing American Trypanosomiasis and Leshmaniasis. On the other hand, C. inophyllum represents an important source for the development of 2nd generation biodiesel. Medicinal and industrial applications of these species may impulse sustainable forest plantations. To our knowledge this is the first scientometric and text mining analysis of chemical and biomedical research on Calophyllum genus, C. brasiliense and C. inophyllum.