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1.
BMC Microbiol ; 20(1): 64, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32209050

RESUMO

BACKGROUND: Biofilm is a fundamental bacterial survival mode which proceeds through three main generalized phases: adhesion, maturation, and dispersion. Lactobacilli spp. (LB) are critical components of gut and reproductive health and are widely used probiotics. Evaluation of time-dependent mechanisms of biofilm formation is important for understanding of host-microbial interaction and development of therapeutic interventions. Time-dependent LB biofilm growth was studied in two systems: large biofilm output in continuous flow system (microfermenter (M), Institute Pasteur, France) and electrical impedance-based real time label-free cell analyzer (C) (xCELLigence, ACEA Bioscience Inc., San Diego, CA). L. plantarum biofilm growth in M system was video-recorded, followed by analyses using IMARIS software (Bitplane, Oxford Instrument Company, Concord, MA, USA). Additionally, whole genome expression and analyses of attached (A) and dispersed (D) biofilm phases at 24 and 48 h were performed. RESULTS: The dynamic of biofilm growth of L. plantarum was similar in both systems except for D phases. Comparison of the transcriptome of A and D phases revealed, that 121 transcripts differ between two phases at 24 h. and 35 transcripts - at 48 h. of M growth. The main pathways, down-regulated in A compared to D phases after 24 h. were transcriptional regulation, purine nucleotide biosynthesis, and L-aspartate biosynthesis, and the upregulated pathways were fatty acid and phospholipid metabolism as well as ABC transporters and purine nucleotide biosynthesis. Four LB species differed in the duration and amplitude of attachment phases, while growth phases were similar. CONCLUSION: LB spp. biofilm growth and propagation area dynamic, time-dependent processes with species-specific and time specific characteristics. The dynamic of LB biofilm growth agrees with published pathophysiological data and points out that real time evaluation is an important tool in understanding growth of microbial communities.


Assuntos
Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Perfilação da Expressão Gênica/métodos , Lactobacillus/fisiologia , Impedância Elétrica , Regulação Bacteriana da Expressão Gênica , Lactobacillus/genética , Análise de Sequência de RNA , Especificidade da Espécie , Fatores de Tempo , Gravação em Vídeo , Sequenciamento do Exoma
2.
Placenta ; 93: 1-7, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32090963

RESUMO

INTRODUCTION: Placental dysfunction is an underlying cause of many major obstetric diseases and treatment options for complications like fetal growth restriction (FGR) are limited .We previously demonstrated nanoparticle delivery of the human insulin-like growth factor 1 (hIGF1) transgene under control of the trophoblast-specific PLAC1 promoter maintains normal fetal growth in a surgically-induced FGR mouse model. However, uptake by human placental syncytiotrophoblast has yet to be determined. METHODS: An ex vivo human placenta perfusion model, term placenta villous fragments, and other in vitro syncytiotrophoblast models were used to determine nanoparticle uptake, transgene expression, and functional responses under oxidative stress conditions. RESULTS: In the ex vivo perfusion, fluorescence from a Texas-Red conjugated nanoparticle increased in maternal perfusate upon nanoparticle addition and declined by the conclusion of the experiment (P < 0.001. Fluorescent histology confirmed localization in the syncytiotrophoblasts. No Texas-Red fluorescence was detected in the fetal perfusate. Transgene expression of hIGF1 in differentiated BeWo cells, isolated primary trophoblasts and fragments was increased compared to untreated (55,000-fold, P = 0.0003; 95-fold, P = 0.003; 400-fold, P < 0.001, respectively). Functionally, increased hIGF1 expression in villous fragments resulted in translocation of glucose transporter 1 to the syncytiotrophoblast cell membrane and under conditions of oxidative stress in BeWo cells, protected against increased cell death (P < 0.01) and decreased mitochondrial activity (P < 0.01). CONCLUSION: The current study confirms that our nanoparticle is capable of uptake in human placental syncytium which results in enhanced transgene expression, functional changes to cellular activity and protection against increased oxidative stress.


Assuntos
Técnicas de Transferência de Genes , Células Gigantes/metabolismo , Fator de Crescimento Insulin-Like I/genética , Nanopartículas , Placenta/metabolismo , Trofoblastos/metabolismo , Adulto , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Células Cultivadas , Portadores de Fármacos/farmacologia , Feminino , Expressão Gênica/efeitos dos fármacos , Células Gigantes/efeitos dos fármacos , Humanos , Recém-Nascido , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Nanopartículas/química , Placenta/citologia , Placenta/efeitos dos fármacos , Gravidez , Transfecção/métodos , Trofoblastos/efeitos dos fármacos , Trofoblastos/fisiologia
3.
Physiol Rep ; 7(6): e14024, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30912236

RESUMO

Poor nutrition during pregnancy is a worldwide public health problem. Maternal nutrient reduction (MNR) is associated with maternal and fetal stress and a sex-dependent decrease in nonhuman primate (NHP) cognitive performance. Early life stress potentiates epileptogenesis in a sex-specific manner, and temporal lobe (TL) epilepsy is associated with neurocognitive disorders. The endogenous cannabinoid system (ECS) demonstrates remarkable developmental changes and plays a key role in aging-related diseases (e.g., dementia). Baboons have been studied as a natural model of epilepsy and express all ECS system components. We therefore evaluated baboon fetal temporal cortex ECS ontogenic and MNR-dependent changes. At 120 days gestational age (dGA) (term 185 days), maternal, fetal, and placental morphometry were similar between control and MNR pregnancies. MNR maternal weight gain was decreased compared with controls at 165 dGA independent of fetal sex. In male fetuses, expression of ECS synthesizing and degrading enzymes was gestational age-dependent, with the exception of fatty acid amide hydrolase (FAAH). MNR had a sex-specific effect on the protein expression of CB1R during development: CB1R protein expression was decreased in fetal temporal cortex of male fetuses at 120 and 140 dGA. Our data reveal that the MNR has sex-specific effects on temporal cortical expression of the ECS in baboon offspring and shows vulnerability of ECS in male fetuses during gestation.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Restrição Calórica , Endocanabinoides/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Lobo Temporal/metabolismo , Amidoidrolases/genética , Amidoidrolases/metabolismo , Animais , Endocanabinoides/genética , Feminino , Desenvolvimento Fetal , Regulação da Expressão Gênica no Desenvolvimento , Regulação Enzimológica da Expressão Gênica , Idade Gestacional , Masculino , Papio , Gravidez , Receptor CB1 de Canabinoide/genética , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/genética , Receptor CB2 de Canabinoide/metabolismo , Fatores Sexuais , Transdução de Sinais , Lobo Temporal/crescimento & desenvolvimento
4.
Acta Diabetol ; 56(2): 227-236, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30673859

RESUMO

AIMS: Ectopic fat is a recognized contributor to insulin resistance and metabolic dysfunction, while the role of fat deposition inside intestinal wall tissue remains understudied. We undertook this study to directly quantify and localize intramural fat deposition in duodenal tissue and determine its association with adiposity. METHODS: Duodenal tissues were collected from aged (21.2 ± 1.3 years, 19.5 ± 3.1 kg, n = 39) female baboons (Papio sp.). Fasted blood was collected for metabolic profiling and abdominal circumference (AC) measurements were taken. Primary tissue samples were collected at the major duodenal papilla at necropsy: one full cross section was processed for hematoxylin and eosin staining and evaluated; a second full cross section was processed for direct chemical lipid analysis on which percentage duodenal fat content was calculated. RESULTS: Duodenal fat content obtained by direct tissue quantification showed considerable variability (11.95 ± 6.93%) and was correlated with AC (r = 0.60, p < 0.001), weight (r = 0.38, p = 0.02), leptin (r = 0.63, p < 0.001), adiponectin (r = - 0.32, p < 0.05), and triglyceride (r = 0.41, p = 0.01). The relationship between duodenal fat content and leptin remained after adjusting for body weight and abdominal circumference. Intramural adipocytes were found in duodenal sections from all animals and were localized to the submucosa. Consistent with the variation in tissue fat content, the submucosal adipocytes were non-uniformly distributed in clusters of varying size. Duodenal adipocytes were larger in obese vs. lean animals (106.9 vs. 66.7 µm2, p = 0.02). CONCLUSIONS: Fat accumulation inside the duodenal wall is strongly associated with adiposity and adiposity related circulating biomarkers in baboons. Duodenal tissue fat represents a novel and potentially metabolically active site of ectopic fat deposition.


Assuntos
Adiposidade , Duodeno/patologia , Gordura Intra-Abdominal/patologia , Obesidade/patologia , Adiponectina/sangue , Animais , Feminino , Gordura Intra-Abdominal/metabolismo , Leptina/sangue , Papio , Triglicerídeos/sangue
5.
J Med Primatol ; 48(1): 68-73, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30246873

RESUMO

We present a case of hepatocellular carcinoma (HCC) in the placenta of healthy baboon (Papio spp.). Grossly, the fetal, maternal, and placental tissues were unremarkable. Histologically, the placenta contained an unencapsulated, poorly demarcated, infiltrative, solidly cellular neoplasm composed of cells that resembled hepatocytes. The neoplastic cells were diffusely positive for vimentin and focally positive for Ae1/Ae3, Arginase -1, glutamine synthetase, and CD10, and negative for ER, vascular markers (CD31 and D240), S100, glypican, C-reactive protein, FABP, desmin, and beta-catenin; INI1 positivity was similar to non-neoplastic tissues. The case likely represents a unique subtype of HCC.


Assuntos
Carcinoma Hepatocelular/veterinária , Doenças dos Macacos/patologia , Papio , Placenta/patologia , Animais , Animais de Zoológico , Carcinoma Hepatocelular/classificação , Carcinoma Hepatocelular/patologia , Feminino , Doenças dos Macacos/classificação , Gravidez
6.
Medicine (Baltimore) ; 97(39): e12392, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30278515

RESUMO

Imaging of placental tissues is a difficult task, because of specific for this organ complex multicellular and 3D tissue structure. The tissue clearing systems (X-CLARITY) system is a valuable tool for the examining the expression of molecular pathways in whole tissues and organs, originally developed for brain imaging.In the present report, we utilized this technology for the examination of placental vasculature and protein expression in perfused human placental tissue.The placental tissue was sufficiently cleared with preservation of endothelial staining and fluorescent markers, allowing visualization using confocal microscopy. The CLARITY method and X-CLARITY system is a valuable tool in placental imaging.


Assuntos
Imunofluorescência/métodos , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Placenta/diagnóstico por imagem , Feminino , Humanos , Microscopia Confocal/métodos , Placenta/irrigação sanguínea , Placenta/metabolismo , Gravidez
7.
J Med Primatol ; 47(6): 393-401, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30039863

RESUMO

INTRODUCTION: Gut microbial communities are critical players in the pathogenesis of obesity. Pregnancy is associated with increased bacterial load and changes in gut bacterial diversity. Sparse data exist regarding composition of gut microbial communities in obesity combined with pregnancy. MATERIAL AND METHODS: Banked tissues were collected under sterile conditions during necropsy, from three non-obese (nOb) and four obese (Ob) near-term pregnant baboons. Sequences were assigned taxonomy using the Ribosomal Database Project classifier. Microbiome abundance and its difference between distinct groups were assessed by a nonparametric test. RESULTS: Three families predominated in both the nOb and Ob colonic microbiome: Prevotellaceae (25.98% and 32.71% respectively), Ruminococcaceae (12.96% and 7.48%), and Lachnospiraceae (8.78% and 11.74%). Seven families of the colon microbiome displayed differences between Ob and nOb groups. CONCLUSION: Changes in gut microbiome in pregnant obese animals open the venue for dietary manipulation in pregnancy.


Assuntos
Bactérias/isolamento & purificação , Microbioma Gastrointestinal , Doenças dos Macacos/microbiologia , Obesidade/microbiologia , Papio/microbiologia , Animais , Bactérias/classificação , Feminino , Gravidez
8.
J Med Primatol ; 47(3): 192-197, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29504143

RESUMO

Disorders of sexual development are rare in non-human primates. We report a case of true hermaphroditism in a 19-year-old, nulliparous, female baboon (Papio spp.). At necropsy, the animal was obese with adequate muscle mass and hydration. Reproductive organs appeared normal with the exception of 2 firm nodular structures in the myometrium (1-1.5 cm diameter) and a thickened, dark endocervical mucosa. Histologically, both gonads were ovotestes and contained discrete areas of ovarian and testicular tissue. There were follicles in various stages of development surrounded by ovarian stroma. Other areas contained hypoplastic seminiferous tubules lined by Sertoli cells, but lacked germ cells and spermatozoa. The uterine lesions were consistent with adenomyosis and cystic endometrial hyperplasia. Cervical lesions were consistent with atypical glandular hyperplasia and squamous metaplasia with dysplasia. We report the first case of ovotesticular disorder of sexual development (OT-DSD), or true hermaphroditism in a baboon.


Assuntos
Doenças dos Macacos/patologia , Transtornos Ovotesticulares do Desenvolvimento Sexual/patologia , Papio , Animais , Feminino
9.
Subst Abus ; 39(1): 9-13, 2018 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-28723278

RESUMO

BACKGROUND: The condition termed cannabinoid hyperemesis syndrome (CHS) was characterized a decade ago by Allen et al. and includes cyclic episodes of nausea and vomiting and the learned behavior of hot bathing in individuals with chronic cannabis abuse. During pregnancy, the differential diagnosis of this syndrome is challenging, since it can be masked by typical symptoms of early pregnancy or by hyperemesis gravidarum, a complication of early pregnancy associated with excessive nausea and vomiting. CASE DESCRIPTION: The authors herein describe the case of a 21-year-old primigravida patient diagnosed with hyperemesis gravidarum at 6 weeks of gestation and with preeclampsia at 35 weeks. At 30 weeks of gestation, a drug screen was performed that was positive for cannabis; therefore, a diagnosis of CHS was made. After labor induction, the patient delivered an infant who developed normally and had a negative drug test of the umbilical cord blood. Esophagogastroduodenoscopy was performed 9 days post delivery, with biopsies taken of the duodenal, gastric, and esophageal tissues. Moderate chronic gastritis with lymphoid aggregates and slight acute inflammation were noticed, whereas no malignancy, dysplasia, or goblet cell metaplasia was detected. A number of Helicobacter-like organisms were identified by H. pylori immunostaining. CONCLUSION: Presented here is the first case reporting an association of chronic cannabis use with H. pylori colonization and preeclampsia in pregnancy, which brings to light the possible involvement of a cannabinoid-related pathway in the link between pregnancy-specific complications and bacterial colonization.


Assuntos
Canabinoides/efeitos adversos , Infecções por Helicobacter/induzido quimicamente , Hiperêmese Gravídica/induzido quimicamente , Pré-Eclâmpsia/induzido quimicamente , Feminino , Infecções por Helicobacter/complicações , Helicobacter pylori/isolamento & purificação , Humanos , Hiperêmese Gravídica/complicações , Gravidez , Síndrome , Adulto Jovem
10.
J Perinat Med ; 46(5): 465-488, 2018 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-28710882

RESUMO

Mid-trimester preterm premature rupture of membranes (PPROM), defined as rupture of fetal membranes prior to 28 weeks of gestation, complicates approximately 0.4%-0.7% of all pregnancies. This condition is associated with a very high neonatal mortality rate as well as an increased risk of long- and short-term severe neonatal morbidity. The causes of the mid-trimester PPROM are multifactorial. Altered membrane morphology including marked swelling and disruption of the collagen network which is seen with PPROM can be triggered by bacterial products or/and pro-inflammatory cytokines. Activation of matrix metalloproteinases (MMP) have been implicated in the mechanism of PPROM. The propagation of bacteria is an important contributing factor not only in PPROM, but also in adverse neonatal and maternal outcomes after PPROM. Inflammatory mediators likely play a causative role in both disruption of fetal membrane integrity and activation of uterine contraction. The "classic PPROM" with oligo/an-hydramnion is associated with a short latency period and worse neonatal outcome compared to similar gestational aged neonates delivered without antecedent PPROM. The "high PPROM" syndrome is defined as a defect of the chorio-amniotic membranes, which is not located over the internal cervical os. It may be associated with either a normal or reduced amount of amniotic fluid. It may explain why sensitive biochemical tests such as the Amniosure (PAMG-1) or IGFBP-1/alpha fetoprotein test can have a positive result without other signs of overt ROM such as fluid leakage with Valsalva. The membrane defect following fetoscopy also fulfils the criteria for "high PPROM" syndrome. In some cases, the rupture of only one membrane - either the chorionic or amniotic membrane, resulting in "pre-PPROM" could precede "classic PPROM" or "high PPROM". The diagnosis of PPROM is classically established by identification of nitrazine positive, fern positive watery leakage from the cervical canal observed during in specula investigation. Other more recent diagnostic tests include the vaginal swab assay for placental alpha macroglobulin-1 test or AFP and IGFBP1. In some rare cases amniocentesis and infusion of indigo carmine has been used to confirm the diagnosis of PPROM. The management of the PPROM requires balancing the potential neonatal benefits from prolongation of the pregnancy with the risk of intra-amniotic infection and its consequences for the mother and infant. Close monitoring for signs of chorioamnionitis (e.g. body temperature, CTG, CRP, leucocytes, IL-6, procalcitonine, amniotic fluid examinations) is necessary to minimize the risk of neonatal and maternal complications. In addition to delayed delivery, broad spectrum antibiotics of penicillin or cephalosporin group and/or macrolide and corticosteroids have been show to improve neonatal outcome [reducing risk of chorioamnionitis (average risk ratio (RR)=0.66), neonatal infections (RR=0.67) and abnormal ultrasound scan of neonatal brain (RR=0.67)]. The positive effect of continuous amnioinfusion through the subcutaneously implanted perinatal port system with amniotic fluid like hypo-osmotic solution in "classic PPROM" less than 28/0 weeks' gestation shows promise but must be proved in future prospective randomized studies. Systemic antibiotics administration in "pre-PPROM" without infection and hospitalization are also of questionable benefit and needs to be further evaluated in well-designed randomized prospective studies to evaluate if it is associated with any neonatal benefit as well as the relationship to possible adverse effect of antibiotics on to fetal development and neurological outcome.


Assuntos
Ruptura Prematura de Membranas Fetais/etiologia , Ruptura Prematura de Membranas Fetais/terapia , Feminino , Ruptura Prematura de Membranas Fetais/classificação , Ruptura Prematura de Membranas Fetais/diagnóstico , Humanos , Gravidez , Segundo Trimestre da Gravidez
11.
Am J Physiol Endocrinol Metab ; 314(4): E322-E333, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29138223

RESUMO

Maternal obesity in pregnancy has been linked to a spectrum of adverse developmental changes. Involvement of eCBs in obesity is well characterized. However, information regarding eCB physiology in obesity associated with pregnancy is sparse. This study evaluated fetomaternal hepatic, systemic, and placental eCB molecular changes in response to maternal consumption of a HFD. From ≥9 mo before conception, nonpregnant baboons ( Papio spp.) were fed a diet of either 45 (HFD; n = 11) or 12% fat or a control diet (CTR; n = 11), and dietary intervention continued through pregnancy. Maternal and fetal venous plasma samples were evaluated using liquid chromatography-mass spectrometry to quantify AEA and 2-AG. Placental, maternal and fetal hepatic tissues were analyzed using RT-PCR, Western blot, and immunohistochemistry. mRNA and protein expression of endocannabinoid receptors (CB1R and CB2R), FAAH, DAGL, MAGL, and COX-2 were determined. Statistical analyses were performed with the nonparametric Scheirer-Ray-Hare extension of the Kruskal-Wallis test to analyze the effects of diet (HFD vs. CTR), fetal sex (male vs. female), and the diet × sex interaction. Fetal weight was influenced by fetal sex but not by maternal diet. The increase in maternal weight in animals fed the HFD vs. the CTR diet approached significance ( P = 0.055). Maternal circulating 2-AG concentrations increased, and fetal circulating concentrations decreased in the HFD group, independently of fetal sex. CB1R receptor expression was detected in syncytiotrophoblasts (HFD) and the fetal endothelium (CTR and HFD). Placental CB2R protein expression was higher in males and lower in female fetuses in the HFD group. Fetal hepatic CB2R, FAAH, COX-2 (for both fetal sexes), and DAGLα (in male fetuses) protein expression decreased in the HFD group compared with the CTR group. We conclude that consumption of a HFD during pregnancy results in fetal systemic 2-AG and hepatic eCB deficiency.


Assuntos
Dieta Hiperlipídica , Gorduras na Dieta/farmacologia , Endocanabinoides/metabolismo , Fígado/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Materna , Placenta/efeitos dos fármacos , Animais , Dieta Hiperlipídica/efeitos adversos , Feminino , Fígado/metabolismo , Masculino , Fenômenos Fisiológicos da Nutrição Materna/efeitos dos fármacos , Troca Materno-Fetal/efeitos dos fármacos , Papio , Placenta/metabolismo , Gravidez , Receptor CB1 de Canabinoide/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
Med Hypotheses ; 96: 35-38, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27959272

RESUMO

The theory of a fetal origin of adult diseases links many pathological conditions to very early life events and is known as a "developmental programming" phenomenon. The mechanisms of this phenomenon are not quite understood and have been explained by inflammation, stress, etc. In particular the epidemic of obesity, with more than 64% of women being overweight or obese, has been associated with conditions in later life such as mental disorders, diabetes, asthma, and irritable bowel syndrome. Interestingly, these diseases were classified a decade ago as Clinical Syndrome of Endocannabinoid Deficiency (CECD), which was first described by Russo in 2004. Cannabinoids have been used for the treatment of chronic pain for millenniums and act through the mechanism of "kick-starting" the components of the endogenous cannabinoid system (ECS). ECS is a pharmacological target for the treatment of obesity, inflammation, cardiovascular and neuronal damage, and pain. We hypothesize that the deteriorating effect of maternal obesity on offspring health is explained by the mechanism of Fetal Syndrome of Endocannabinoid Deficiency (FSECD), which accompanies maternal obesity. Here we provide support for this hypothesis.


Assuntos
Endocanabinoides/deficiência , Obesidade/complicações , Complicações na Gravidez , Adulto , Animais , Ácidos Araquidônicos/sangue , Asma/complicações , Transtorno do Espectro Autista/complicações , Canabinoides/efeitos adversos , Endocanabinoides/sangue , Feminino , Transtornos da Nutrição Fetal , Glicerídeos/sangue , Humanos , Resistência à Insulina , Síndrome do Intestino Irritável/complicações , Modelos Teóricos , Fenótipo , Alcamidas Poli-Insaturadas/sangue , Gravidez , Síndrome , Adulto Jovem
15.
Neurotoxicol Teratol ; 58: 23-30, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27327781

RESUMO

INTRODUCTION: The consumption of marijuana (exogenous cannabinoid) almost doubled in adults during last decade. Consumption of exogenous cannabinoids interferes with the endogenous cannabinoid (or "endocannabinoid" (eCB)) system (ECS), which comprises N-arachidonylethanolamide (anandamide, AEA), 2-arachidonoyl glycerol (2-AG), endocannabinoid receptors (cannabinoid receptors 1 and 2 (CB1R and CB2R), encoded by CNR1 and CNR2, respectively), and synthesizing/degrading enzymes (FAAH, fatty-acid amide hydrolase; MAGL, monoacylglycerol lipase; DAGL-α, diacylglycerol lipase-alpha). Reports regarding the toxic and therapeutic effects of pharmacological compounds targeting the ECS are sometimes contradictory. This may be caused by the fact that structure of the eCBs varies in the species studied. OBJECTIVES: First: to clone and characterize the cDNAs of selected members of ECS in a non-human primate (baboon, Papio spp.), and second: to compare those cDNA sequences to known human structural variants (single nucleotide polymorphisms and haplotypes). MATERIALS AND METHODS: Polymerase chain reaction-amplified gene products from baboon tissues were transformed into Escherichia coli. Amplicon-positive clones were sequenced, and the obtained sequences were conceptually translated into amino-acid sequences using the genetic code. RESULTS: Among the ECS members, CNR1 was the best conserved gene between humans and baboons. The phenotypes associated with mutations in the untranslated regions of this gene in humans have not been described in baboons. One difference in the structure of CNR2 between humans and baboons was detected in the region with the only known clinically relevant polymorphism in a human receptor. All of the differences in the amino-acid structure of DAGL-α between humans and baboons were located in the hydroxylase domain, close to phosphorylation sites. None of the differences in the amino-acid structure of MAGL observed between baboons and humans were located in the area critical for enzyme function. CONCLUSION: The evaluation of the data, obtained in non-human primate model of cannabis-related developmental exposure should take into consideration possible evolutionary-determined species-specific differences in the CB1R expression, CB2R transduction pathway, and FAAH and DAGLα substrate-enzyme interactions.


Assuntos
Endocanabinoides/genética , Modelos Animais , Pesquisa Translacional Biomédica , Amidoidrolases/genética , Animais , Humanos , Lipase Lipoproteica/genética , Fígado/metabolismo , Monoacilglicerol Lipases/genética , Papio , Receptor CB1 de Canabinoide/genética , Receptor CB2 de Canabinoide/genética , Especificidade da Espécie
16.
Sci Rep ; 6: 26817, 2016 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-27226349

RESUMO

Evolutionary approaches are powerful tools for understanding human disorders. The composition of vaginal microbiome is important for reproductive success and has not yet been characterized in the contexts of social structure and vaginal pathology in non-human primates (NHPs). We investigated vaginal size, vulvovaginal pathology and the presence of the main human subtypes of Lactobacillus spp./ BV-related species in the vaginal microflora of baboons (Papio spp.). We performed morphometric measurements of external and internal genitalia (group I, n = 47), analyzed pathology records of animals from 1999-2015 (group II, n = 64 from a total of 12,776), and evaluated vaginal swabs using polymerase chain reaction (PCR) (group III, n = 14). A total of 68 lesions were identified in 64 baboons. Lactobacillus iners, Gardnerella vaginalis, Atopobium vaginae, Megasphaera I, and Megasphaera II were not detected. L. jensenii, L. crispatus, and L. gasseri were detected in 2/14 (14.2%), 1/14 (7.1%), and 1/14 (7.1%) samples, respectively. BVAB2 was detected in 5/14 (35.7%) samples. The differences in the vaginal milieu between NHP and humans might be the factor associated with human-specific pattern of placental development and should be taken in consideration in NHP models of human pharmacology and microbiology.


Assuntos
Evolução Biológica , Disbiose/microbiologia , Disbiose/veterinária , Lactobacillus/isolamento & purificação , Microbiota , Papio/microbiologia , Doenças dos Primatas/microbiologia , Vagina/microbiologia , Doenças Vaginais/veterinária , Doenças da Vulva/veterinária , Animais , Feminino , Lactobacillus/fisiologia , Tamanho do Órgão , Doenças dos Primatas/patologia , Doenças dos Primatas/virologia , Simplexvirus/isolamento & purificação , Especificidade da Espécie , Vagina/anatomia & histologia , Doenças Vaginais/microbiologia , Doenças Vaginais/patologia , Doenças Vaginais/virologia , Vulva/anatomia & histologia , Vulva/microbiologia , Doenças da Vulva/microbiologia , Doenças da Vulva/patologia , Doenças da Vulva/virologia
17.
Comp Med ; 66(2): 137-42, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27053568

RESUMO

Obesity is associated with vitamin D deficiency, which can lead to serious problems during pregnancy. However, the mechanisms of the deficiency and guidelines for vitamin D supplementation during pregnancy are not established yet, and variations in environmental exposures combined with the difficulties of performing research in pregnant women are obstacles in the evaluation of vitamin D metabolism. Baboons (Papio spp.) are an excellent, well-established model for reproductive research and represent a unique opportunity to study vitamin D metabolism in a controlled environment. This study used secondary data and specimen analysis as well as a novel experimental design to evaluate pregnant and nonpregnant baboons that were or were not exposed to sunlight while they were obese and after weight reduction. Daily D3 intake was 71% higher in nonpregnant obese baboons than in their nonobese counterparts, but serum vitamin D concentrations did not differ between these populations. In addition, serum 25-hydroxyvitamin D concentrations correlated negatively with the obesity index. This report is the first to show the effect of obesity and pregnancy on vitamin D concentrations in a NHP population. These data underline the importance of adequate vitamin D supplementation in obese animals.


Assuntos
Obesidade/sangue , Papio , Prenhez/sangue , Deficiência de Vitamina D , Vitamina D/análogos & derivados , Vitaminas/sangue , Animais , Feminino , Abrigo para Animais , Humanos , Modelos Animais , Gravidez , Vitamina D/sangue , Vitamina D/uso terapêutico , Deficiência de Vitamina D/sangue , Vitaminas/uso terapêutico
18.
Case Rep Womens Health ; 12: 5-10, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29629302

RESUMO

BACKGROUND: Coccidioidomycosis is an endemic fungal infection found most commonly in the Southwestern United States, Northwestern Mexico, and parts of Central and South America. Although infection is relatively uncommon during pregnancy, it is imperative to have an index of suspicion in order to diagnose and begin timely treatment to prevent dissemination and dire consequences. CASE REPORT: A 33-year-old Hispanic female was evaluated after she was involved in an automobile accident. Radiographic evaluation showed a 3.2 × 3.2 cm cavitary thick-walled lesion. A biopsy was negative for malignancy. Evaluation was positive for coccidioidomycosis by complement fixation reaction. Four months later, the patient presented 7 weeks into a pregnancy with massive hemoptysis. Bronchoscopy revealed bleeding from the right upper lobe and emergency embolization was performed. The patient had a spontaneous abortion 9 days after admission. The right upper and middle lobes of the lung were resected due to continuous bleeding. A subsequent pregnancy was un-eventful. Coccidioidomycosis titers remained negative throughout the second pregnancy. DISCUSSION: This case demonstrates the potential for severe pulmonary coccidioidomycosis and vascular strain of pregnancy-associated vascular expansion in the first trimester of pregnancy and the possibility of a favorable pregnancy outcome in subsequent pregnancies after appropriate treatment. The route of feto-maternal transmission and placental lesions in coccidioidomycosis are discussed.

19.
Placenta ; 36(12): 1450-4, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26565601

RESUMO

INTRODUCTION: To assess the effects of selective reduced uterine perfusion pressure (SRUPP) in pregnant rats. METHODS: 20 pregnant Sprague-Dawley rats were allocated either to an intervention group, exposed to SRUPP (n = 10) or a control group, exposed to sham surgery (n = 10). Such procedures were performed on gestational day (GD) 14. The Mean arterial pressure (MAP) was measured on GD14 (before surgery) and GD20. We measured 18 h proteinuria on GD20. On GD21, mean fetal (MFW) and placental (MPW) weights were obtained. Oxidative stress and angiogenic markers were measured in placental tissue and urine. Mann Whitney U or Independent samples T test were used when appropriate. A two-sided P < 0.05 indicated statistical significance. RESULTS: MAP on GD20 was higher in the intervention group (109 ± 1.7 mmHg) when compared with the control group (83 ± 1.5 mmHg) (P = 0.002). There was no significant difference in urinary protein excretion (117 ± 3.1 mg/24 h versus 136 mg ± 2.8/24 h, P = 0.18), MFW (4.14 ± 0.05 versus 4.39 ± 0.04 g, P = 0.19) or MPW (0.43 ± 0.008 versus 0.44 ± 0.006 g, P = 0.73) between the intervention and the control groups, respectively. The oxidative stress was increased; whereas, the sFLT1 expression was not increased when the SRUPP group was compared with controls. DISCUSSION: SRUPP is associated with an increase in maternal MAP and oxidative stress and therefore it may become a useful tool in the study of pregnancy-related hypertensive disorders.


Assuntos
Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Proteinúria/metabolismo , Útero/metabolismo , Animais , Biomarcadores/metabolismo , Pressão Sanguínea , Modelos Animais de Doenças , Feminino , Estresse Oxidativo/fisiologia , Perfusão , Placenta/fisiopatologia , Pré-Eclâmpsia/fisiopatologia , Gravidez , Proteinúria/fisiopatologia , Ratos Sprague-Dawley , Útero/fisiopatologia
20.
Biol Res ; 48: 31, 2015 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-26063455

RESUMO

BACKGROUND: Chemerin, encoded by the retinoic acid receptor responder 2 (RARRES2) gene is an adipocytesecreted protein with autocrine/paracrine functions in adipose tissue, metabolism and inflammation with a recently described function in vascular tone regulation, liver, steatosis, etc. This molecule is believed to represent a critical endocrine signal linking obesity to diabetes. There are no data available regarding evolution of RARRES2 in non-human primates and great apes. Expression profile and orthology in RARRES2 genes are unknown aspects in the biology of this multigene family in primates. Thus; we attempt to describe expression profile and phylogenetic relationship as complementary knowledge in the function of this gene in primates. To do that, we performed A RT-PCR from different tissues obtained during necropsies. Also we tested the hypotheses of positive evolution, purifying selection, and neutrality. And finally a phylogenetic analysis was made between primates RARRES2 protein. RESULTS: RARRES2 transcripts were present in liver, lung, adipose tissue, ovary, pancreas, heart, hypothalamus and pituitary tissues. Expression in kidney and leukocytes were not detectable in either species. It was determined that the studied genes are orthologous. CONCLUSIONS: RARRES2 evolution fits the hypothesis of purifying selection. Expression profiles of the RARRES2 gene are similar in baboons and chimpanzees and are also phylogenetically related.


Assuntos
Evolução Molecular , Pan troglodytes/genética , Papio/genética , Receptores do Ácido Retinoico/genética , Animais , Sequência de Bases , Feminino , Masculino , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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