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1.
Int. j. morphol ; 38(5): 1250-1257, oct. 2020. tab, graf
Article in English | LILACS | ID: biblio-1134433

ABSTRACT

SUMMARY: Residential heating with wood is an important source of ambient air pollution. Evidence links air pollution to serious health effects such as respiratory and cardiovascular mortality and morbidity. We hypothesized that prenatal exposure to wood smoke pollution causes morphological changes in the development of the rat lung, leading to altered lung structure and function during later life. We presumed that analysis of the fetal lung stereology provides novel insights into the underlying processes mediating particulate matter associated developmental changes and damage. The objective of the study was to investigate the effects of exposure during gestational period to wood smoke pollution on lung fetal morphology. To test this, pregnant rats were exposed during pregestational and gestational periods to wood smoke pollution. Complete lungs samples were obtained from 24 fetus from healthy female G3 rats subjected to cesarean at 19 days post-fecundation. The lungs were prepared for histological and stereological analysis. The volume fraction of terminal bronchioles VV [tb, lung] and volume fraction of parenchyma VV [par, lung], surface density of terminal bronchioles SV [tb, lung] as well as numerical density of bronchiolar exocrinocytes NA [ec,lung] were calculated by light microscopy. Statistical analysis detected significant differences between groups in volume density VV [tb, lung; %] (p=0.0012) and surface density SV [tb, lung; mm2/mm3] (p<0.0001) of the terminal bronchioles. However, it did not show differences between groups in the stereological parameter volume density VV [par, lung; %] (p=0.0838) and numerical density of bronchiolar exocrinocytes NA [ec,lung; nº/mm2] (p=0.0705). The analysis of the evidence obtained indicates that exposure to environmental pollution was affects lung maturation, and particularly the proportion and area of terminal bronchioles in the fetal lung. In conclusion, maternal exposure to wood smoke pollution during pregnancy was associated with a decrease in the lower conducting airways of lungs, which, according to urban pollution studies, could be related to early childhood lower respiratory illness. The public health implications of this study are that reducing or avoiding exposure to wood smoke is important before and during pregnancy.


RESUMEN: La calefacción residencial con leña es una fuente importante de contaminación ambiental. La evidencia vincula la contaminación del aire con graves efectos sobre la salud, como la mortalidad y la morbilidad respiratoria y cardiovascular. Hipotetizamos que la exposición prenatal a la contaminación por humo de leña causa cambios en el desarrollo del pulmón de rata, lo que conduce a una morfo-función pulmonar alteradas durante la vida posterior, creemos que el análisis de la estereología pulmonar fetal proporcionará nuevos conocimientos sobre los procesos subyacentes que median esos cambios. El objetivo del estudio fue investigar los efectos de la exposición prenatal a la contaminación ambiental por humo de leña sobre la morfología pulmonar fetal. Ratas preñadas fueron expuestas durante los períodos pregestacional y gestacional a la contaminación por humo de leña. En fetos de 19 días post-fecundación fue obtenido el pulmón para análisis histológico y estereológico. Fue determinado la fracción de volumen de bronquiolos terminales VV [tb, pulmón], fracción de volumen del parénquima VV [par, pulmón], densidad superficial de los bronquiolos terminales SV [tb, pulmón] así como la densidad numérica de exocrinocitos NA [ec, pulmón]. El análisis estadístico detectó diferencias significativas entre grupos en la densidad de volumen V [tb, pulmón; %] (p=0,0012) y densidad superficial SV [tb, pulmón; mm2/mm3] (p<0,0001) de los bronquiolos terminales. Sin embargo, no demostró diferencias entre grupos en la densidad de volumen VV [par, pulmón; %] (p=0,0838) y numérica de exocrinocitos bronquiolares NA [ec, pulmón; nº / mm ] (p=0,0705). El análisis de la evidencia obtenida indica que la exposición a la contaminación ambiental afectó la maduración pulmonar, y particularmente la proporción y área de bronquiolos terminales en el pulmón fetal. En conclusión, la exposición materna a la contaminación por humo de leña durante la gestación se asoció a una disminución de las vías respiratorias conductoras de aire en pulmón, lo que, según estudios de contaminación urbana, podría estar relacionado con enfermedades de las vías respiratorias inferiores en la primera infancia. Las implicaciones para la salud pública de este estudio son que reducir o evitar la exposición al humo de leña es importante previo y durante la gestación. Por otro lado, la contaminación por humo de leña tiene un gran impacto en la salud pública que, en teoría, es posible prevenir.


Subject(s)
Animals , Female , Pregnancy , Rats , Air Pollutants/toxicity , Air Pollution/adverse effects , Lung/drug effects , Smoke/adverse effects , Wood , Analysis of Variance , Maternal Exposure/adverse effects , Disease Models, Animal , Environmental Exposure , Particulate Matter/toxicity , Fetus/drug effects , Heating , Lung/pathology
2.
Int. j. morphol ; 38(5): 1356-1364, oct. 2020. tab, graf
Article in English | LILACS | ID: biblio-1134448

ABSTRACT

SUMMARY: Studies in humans showed that prenatal exposure to urban air pollution (AP) influences fetal development, and increases the incidence of adverse pregnancy outcomes and some diseases in postnatal life. However, most of these were performed in environments where the main source of environmental particulate matters (PM) emission is diesel combustion by motor vehicles and industries, thereby ignoring the effects produced by wood smoke pollution. We hypothesized that morphological changes in the placenta could contribute to the reduction in fetal size associated with different periods of exposure to AP produced by wood smoke pollution prior to and during pregnancy. The objective of the study was to investigate the quantitative effects of long-term exposure to environmental levels of wood smoke pollution on the macroscopic and microscopic morphology of the placenta in rats. To test this, pregnant rats were exposed during pregestational and gestational periods to wood smoke pollution in indoor and outdoor environments. At 19 days of gestation, the placentas were obtained by caesarean and were prepared for histological, planimetric and stereological analysis. The volume and proportions of the placental compartments were estimated. In addition, stereological estimators in fetal capillaries were calculated in the labyrinth region. Crown rump length, fetus weight and litter weight were influenced by pregestational and gestational exposure periods. Exposure to wood smoke pollution during pregestational period has significant effect on the volume of the placenta, and consequently on fetal height. In conclusion, this study demonstrated that long-term outdoor exposure to wood smoke pollution from residential heating affects fetal health, decreasing the absolute volume of the entire placenta and the placental interface between the mother and fetus, decreasing the total volume of blood vessels present in the labyrinth region ofthe placenta and affecting the size of the fetus.


RESUMEN: Estudios en humanos demostraron que la exposición prenatal a la polución del aire urbano influye en el desarrollo fetal y aumenta la incidencia de resultados adversos de la gestación y algunas enfermedades postnatales. Sin embargo, la mayoría de ellos fueron realizados en entornos donde la principal fuente de emisión de material particulado, fue la combustión de petróleo por vehículos a motor e industrias, ignorando los efectos producidos por el humo de leña producido por la calefacción intradomiciliaria. Hipotetizamos respecto a que los cambios de la placenta contribuirían a la disminución del tamaño fetal relacionado a los períodos de exposición al humo de leña durante los periodos pregestacional y gestacional. El objetivo del estudio fue investigar los efectos cuantitativos de la exposición al humo de leña sobre la morfología macroscópica y microscópica en placenta de ratas. Para probar esto, ratas preñadas fueron expuestas durante los períodos pregestacional y gestacional a la contaminación por humo de leña en ambientes interiores y exteriores. A los 19 días de gestación, las placentas fueron obtenidas por cesárea y fueron preparadas para un análisis histológico, planimétrico y estereológico. Fue estimado el volumen absoluto y las proporciones de los compartimentos placentarios. Además, fueron calculados estimadores estereológicos en capilares fetales del laberinto y trofoblasto. La longitud, el peso del feto y el peso de la camada fueron influenciados por los períodos de exposición pregestacional y gestacional. La exposición a la contaminación por humo de leñá durante el período pregestacional tuvo un efecto significativo en el volumen de la placenta y, en consecuencia, en la altura del feto. En conclusión, este estudio demostró que la exposición a largo plazo al humo de leña afecta la salud del feto, disminuyendo el volumen absoluto de la placenta, además, afecta la interfaz placentaria entre la madre y feto, disminuyendo el volumen total de vasos sanguíneos presentes en la región del laberinto placentario y por consecuente afectando el tamaño del feto.


Subject(s)
Animals , Female , Pregnancy , Rats , Placenta/drug effects , Smoke/adverse effects , Air Pollutants/toxicity , Fetus/drug effects , Wood , Rats, Sprague-Dawley , Maternal Exposure/adverse effects , Combustion/adverse effects , Body Size , Fetal Development/drug effects , Environmental Pollution/adverse effects , Particulate Matter
3.
Hist. ciênc. saúde-Manguinhos ; 27(1): 15-32, jan.-mar. 2020.
Article in Portuguese | LILACS | ID: biblio-1090496

ABSTRACT

Resumo O artigo analisa como o periódico Jornal do Médico, editado na cidade do Porto, em Portugal, divulgou o desastre da talidomida. A pesquisa percorreu as páginas da fonte desde o início de 1960 até o final de 1962. Aqui, objetivam-se apontar e discutir duas questões interligadas: a morosidade em publicar matérias sobre os efeitos deletérios do medicamento, vendido no país sob a denominação Softenon®, e a construção discursiva da isenção da responsabilidade do médico no fenômeno da iatrogenia medicamentosa.


Abstract This article analyzes the way the Porto-based journal Jornal do Médico reported on the thalidomide disaster. The pages of the publication are researched from the beginning of 1960 to the end of 1962 with the aim of identifying and discussing two interconnected questions: the delay in publishing news on the harmful effects of the drug, which was sold in the country under the brand name Softenon®, and the discursive construction of a lack of accountability on the part of physicians for the phenomenon of medication iatrogenesis.


Subject(s)
Humans , Female , Pregnancy , Infant, Newborn , History, 20th Century , Periodicals as Topic/history , Teratogens/history , Thalidomide/history , Abnormalities, Drug-Induced/history , Advertising/history , Portugal/epidemiology , Thalidomide/adverse effects , Abnormalities, Drug-Induced/epidemiology , Editorial Policies , Drug and Narcotic Control/history , Stillbirth , Fetus/drug effects , Sleep Aids, Pharmaceutical/adverse effects , Sleep Aids, Pharmaceutical/history
4.
Rev. bras. anestesiol ; 69(1): 13-19, Jan.-Feb. 2019. tab, graf
Article in English | LILACS | ID: biblio-977430

ABSTRACT

Abstract Background and objectives: Hypothermia occurs in about 60% of patients under anesthesia and is generally not managed properly during short lasting surgical procedures. Hypothermia is associated with adverse clinical outcomes. The current study is designed to assess the effects of crystalloid warming on maternal and fetal outcomes in patients undergoing elective cesarean section with spinal anesthesia. Methods: In this prospective randomized controlled trial, sixty parturients scheduled for elective cesarean section with spinal anesthesia were randomly allocated to receive crystalloid at room temperature or warmed at 37 °C. Spinal anesthesia was performed at L3-L4 interspace with 10 mg of hyperbaric bupivacaine without adding opioids. Core temperature, shivering, and hemodynamic parameters were measured every minute until 10th minute and 5-min intervals until the end of operation. The primary outcome was maternal core temperature at the end of cesarean section. Results: There was no difference for baseline tympanic temperature measurements but the difference was significant at the end of the operation (p = 0.004). Core temperature was 36.8 ± 0.5 °C at baseline and decreased to 36.3 ± 0.5 °C for isothermic warmed crystalloid group and baseline tympanic core temperature was 36.9 ± 0.4 °C and decreased to 35.8 ± 0.7 °C for room temperature group at the end of the operation. Shivering was observed in 43.3% in the control group. Hemodynamic parameter changes and demographic data were not significant between groups. Conclusions: Isothermic warming crystalloid prevents the decrease in core temperature during cesarean section with spinal anesthesia in full-term parturients. Fetal Apgar scores at first and fifth minute are higher with isothermic warming.


Resumo Justificativa e objetivos: A hipotermia ocorre em cerca de 60% dos pacientes sob anestesia e geralmente não é tratada adequadamente durante procedimentos cirúrgicos de curta duração. A hipotermia está associada a desfechos clínicos adversos. O presente estudo teve como objetivo avaliar os efeitos do aquecimento de cristaloides nas condições maternas e fetais em pacientes submetidas à cesariana eletiva com raquianestesia. Métodos: Neste estudo prospectivo, randômico e controlado, 60 parturientes agendadas para cesárea eletiva com raquianestesia foram distribuídas aleatoriamente para receber cristaloides à temperatura ambiente ou aquecidos a 37 °C. A raquianestesia foi realizada no interespaço L3-L4 com 10 mg de bupivacaína hiperbárica sem adição de opioides. Temperatura central, tremores e parâmetros hemodinâmicos foram medidos a cada minuto até o décimo minuto e em intervalos de 5 min até o fim da operação. O desfecho primário foi a temperatura central materna ao final da cesárea. Resultados: Não houve diferença nas mensurações basais da temperatura timpânica, mas a diferença foi significativa no fim da operação (p = 0,004). A temperatura central foi de 36,8 ± 0,5 °C na fase basal e diminuiu para 36,3 ± 0,5 °C no grupo com aquecimento isotérmico de cristaloides e a temperatura basal timpânica foi de 36,9 ± 0,4 °C e diminuiu para 35,8 ± 0,7 °C no grupo sem aquecimento das soluções no fim da operação. Tremores foram observados em 43,3% no grupo controle. Alterações nos parâmetros hemodinâmicos e dados demográficos não foram significantes entre os grupos. Conclusões: O aquecimento isotérmico de cristaloides previne a redução da temperatura central durante a cesariana com raquianestesia em parturientes a termo. Os escores de Apgar para os fetos no primeiro e quinto minutos são maiores com o aquecimento isotérmico.


Subject(s)
Humans , Female , Pregnancy , Adolescent , Adult , Young Adult , Body Temperature/drug effects , Cesarean Section , Double-Blind Method , Fetus/drug effects , Crystalloid Solutions/therapeutic use , Hypothermia/therapy , Anesthesia, Obstetrical/adverse effects , Anesthesia, Spinal/adverse effects , Prospective Studies , Crystalloid Solutions/pharmacology , Hyperthermia, Induced/methods , Middle Aged
5.
Int. j. morphol ; 37(1): 87-92, 2019. tab, graf
Article in English | LILACS | ID: biblio-990010

ABSTRACT

SUMMARY: This study aimed to investigate the toxic effects of cigarette smoke exposure on lung and the protective role of Omega 3 and Vitamin D against these toxic effects biochemically and histologically. 28 pregnant Wistar Albino rats were divided into four groups. The first group was control group; the second group was exposed to smoke of 10 cigarette by puff device 2 hours/day after pregnancy; the third group was exposed to cigarette smoke together with Omega 3 (0.5 mg/kg/day) and the fourth group was exposed to cigarette smoke together with vitamin D (42 microgram/kg/day). Finally, lung tissue sections of the newborn rats were stained with Hemotoxilen eosine and Masson tricromite. Malondialdehyde (MDA) and Fluorescent Oxidation Products (FOU) levels were measured. Fetal weights and the number of fetuses were significantly lower in the group received only cigarette smoke (both p<0.001). Histopathologically, pulmonary volume, number of developed alveols and parenchyma elasticity decreased significantly, meanwhile interstitial tissue increased, elastin and collagen did not develop adequately. Histopathologic changes significantly decreased in the group given Omega 3 and Vitamin D. Statistically, MDA and FOU levels were found to be higher in the group exposed to cigarette smoke compared to the control group, and MDA and FOU levels were lower in the group given Omega 3 along with cigarette smoke (p<0.001). Cigarette smoke caused histologically significant damage to fetal lung tissue, oxidative stress and increased MDA and FOU levels. This damage was significantly reduced with Omega 3 and Vitamine D supplementation. Omega 3 is an important antioxidant; vitamin D has no significant antioxidant effect.


RESUMEN: Este estudio tuvo como objetivo investigar los efectos tóxicos de la exposición al humo de cigarrillo en el pulmón, y el papel protector de Omega 3 y la Vitamina D contra esos efectos. 28 ratas Wistar albino preñadas fueron separadas en cuatro grupos. El primer grupo grupo control; el segundo grupo estuvo expuesto al humo de 10 cigarrillos por dispositivo de inhalación 2 horas / día después de la preñez; el tercer grupo se expuso al humo del cigarrillo junto con Omega 3 (0,5 mg / kg / día) y el cuarto grupo se expuso al humo del cigarrillo junto con vitamina D (42 microgramos / kg / día). Secciones de tejido pulmonar de las ratas recién nacidas se tiñeron con Hematoxilina Eosina y tricrómico de Masson. Se midieron los niveles de malondialdehído (MDA) y productos de oxidación fluorescente (POF). Los pesos fetales y el número de fetos fueron significativamente más bajos en el grupo que recibió solamente humo de cigarrillo (ambos p <0,001). Histopatológicamente, el volumen pulmonar, el número de alveolos desarrollados y la elasticidad del parénquima disminuyeron significativamente; mientras que el tejido intersticial aumentó y la elastina y el colágeno no se desarrollaron adecuadamente. Los cambios histopatológicos disminuyeron significativamente en el grupo que recibió Omega 3 y Vitamina D. Estadísticamente, se encontró que los niveles de MDA y POF eran más altos en el grupo expuesto al humo de cigarrillo en comparación con el grupo control, además los niveles de MDA y POF fueron más bajos en el grupo que recibió Omega 3 junto con el humo del cigarrillo (p <0,001). El humo del cigarrillo causó daños histológicamente significativos en el tejido pulmonar fetal, el estrés oxidativo y el aumento de los niveles de MDA y FOU. Este daño se redujo significativamente con los suplementos de Omega 3 y Vitamina D. El omega 3 es un importante antioxidante; la vitamina D no tiene ningún efecto antioxidante significativo.


Subject(s)
Animals , Female , Pregnancy , Rats , Vitamin D/administration & dosage , Fatty Acids, Omega-3/administration & dosage , Maternal Exposure/adverse effects , Lung Injury/prevention & control , Nicotine/toxicity , Smoke/adverse effects , Analysis of Variance , Rats, Wistar , Oxidative Stress , Lung Injury/chemically induced , Lung Injury/pathology , Fetus/drug effects , Fluorescence , Animals, Newborn , Malondialdehyde/analysis
6.
Rev. bras. ginecol. obstet ; 39(6): 258-264, June 2017. tab
Article in English | LILACS | ID: biblio-898867

ABSTRACT

Abstract Introduction In the pregnancy-puerperal cycle, women may develop complications that require admission to the Intensive Care Unit (ICU). Thus, special attention to pharmacotherapy is necessary, particularly to potential drug interactions (PDIs) and to the effect of the drugs on the fetus and newborn. Objective The aim of this study was to determine the profile of PDIs and the potential risk of drugs used during pregnancy and breastfeeding among patients admitted to the ICU. Methods We conducted an observational, cross-sectional and prospective study, including pregnant and breastfeeding women admitted to the ICU at the Women's Hospital of a university in the city of Campinas, Brazil, for one year. Online databases were used to identify and classify the PDIs and the potential risk of the drugs used during pregnancy and breastfeeding. Results We evaluated 305 prescriptions of 58 women, 31 pregnant and 27 breastfeeding, and 284 (91%) prescriptions presented PDIs. A total of 175 different combinations of PDIs were identified in the prescriptions, and adverse effects caused by the simultaneous use of drugs were not actually observed in the clinical practice. A total of 26 (1.4%) PDIs were classified as contraindicated. We identified 15 (13.8%) drugs prescribed with risk D, and 2 (1.8%) with risk X for pregnant women, as well as 4 (4.9%) drugs prescribed with high risk for breastfeeding women. Conclusions This study demonstrates that there is a high incidence of PDIs in prescriptions. Most drugs used by pregnant and breastfeeding women at the ICU did not present serious risks to their fetus and newborns, but sometimes drugs with risk D or X are necessary in the course of the treatment.


Resumo Introdução No ciclo gravídico-puerperal, as mulheres podem desenvolver complicações que necessitam de internação na Unidade de Terapia Intensiva (UTI). Assim, é necessária uma atenção especial à farmacoterapia, particularmente às interações medicamentosas potenciais (IMPs) e ao risco dos medicamentos para o feto e o recémnascido. Objetivo Determinar o perfil das IMPs e o risco potencial dos medicamentos utilizados durante a gravidez e a amamentação entre as mulheres internadas em UTI. Métodos Foi realizado um corte transversal e prospectivo, observacional, incluindo mulheres grávidas e lactantes internadas na UTI do Hospital da Mulher de uma universidade de Campinas durante um ano. Bases de dados online foram usadas para identificar e classificar as IMPs e o potencial risco de uso de medicamentos durante a gravidez e a amamentação. Resultados Foram avaliadas 305 prescrições de 58 mulheres, 31 grávidas e 27 lactantes, e 284 (91%) prescrições apresentaram IMPs, sendo que 175 combinações diferentes de IMPs foram identificadas nas prescrições, e não foram observados efeitos nocivos pelo uso concomitante dos medicamentos na prática clínica. Um total de 26 (1,4%) IMPs foram classificadas como contraindicadas. Foram identificados 15 (13,8%) medicamentos prescritos com risco D, e 2 (1,8%) com risco X para mulheres grávidas, e foram identificados 4 (4,9%) medicamentos prescritos como de alto risco para as mulheres que estavam amamentando. Conclusões Este estudo demonstra que há uma alta incidência de IMPs nas prescrições. A maioria dos medicamentos utilizados por mulheres grávidas e lactantes em UTI não apresentou sérios riscos para o feto e o recém-nascido, mas às vezes são necessários medicamentos categorizados como risco D ou X.


Subject(s)
Humans , Female , Pregnancy , Adult , Young Adult , Breast Feeding , Drug Interactions , Fetus/drug effects , Cross-Sectional Studies , Prospective Studies , Postpartum Period , Intensive Care Units , Middle Aged
7.
Int. j. morphol ; 35(2): 500-505, June 2017. ilus
Article in English | LILACS | ID: biblio-893011

ABSTRACT

Halphabarol, the active principle of Proximol, is the most potent of the four antispasmodics present in the national desert weed Cymbopogon proximus or ''Halfa Bar''. Halphabarol is of great value for the management of renal colic and in the expulsion of ureteric calculi as it causes dilation of the ureter below the site of calculus while active propulsion is maintained. Evaluation the congenital malformation of proximol in pregnant albino rats during gestation period. The virgin female rats were mated with male rats and the pregnant rats were orally administered a human equivalent dose (0.05 mg/kg) of Proximol from 5th-20th gestation day. At day 20 of pregnancy, all rats were anesthetized to obtained maternal and fetal data. The treatment group displayed some disorders, which can be summarized as growth retardation, external anomalies, embryonic resorption, and skeletal malformation. We concluded that the oral administration of Proximol resulted in embryonic abnormalities and skeletal malformations.


Halphabarol, el principio activo de Proximol, es el más potente de los cuatro antiespasmódicos presentes en la maleza desértica nacional "Cymbopogon proximus" o "Halfa Bar". Halphabarol es de gran utilidad para el manejo de cólicos renales y para la expulsión de cálculos ureterales, ya que causa la dilatación del uréter por debajo del sitio de cálculo mientras se mantiene el mecanismo de propulsión activa. Se realizó una evaluación de la malformación congénita por Proximol en ratas albinas gestantes durante el período de gestación. Las ratas fueron apareadas y a las ratas gestantes se les administró oralmente, del 5 al 20 día de gestación, una dosis de Proximol (0,05 mg / kg), equivalente a la dosis humana. Al día 20 de gestación, todas las ratas fueron anestesiadas para obtener datos maternos y fetales. El grupo de tratamiento mostró algunos trastornos, que pueden resumirse como retraso del crecimiento, anomalías externas, resorción embrionaria y malformación esquelética. Concluimos que la administración oral de Proximol resultó en anomalías embrionarias y malformaciones esqueléticas.


Subject(s)
Animals , Female , Pregnancy , Rats , Congenital Abnormalities/pathology , Cymbopogon , Parasympatholytics/toxicity , Plants, Medicinal/toxicity , Congenital Abnormalities/etiology , Fetus/drug effects , Fetus/pathology , Pregnancy, Animal/drug effects
8.
An. acad. bras. ciênc ; 89(2): 1073-1084, Apr.-June 2017. tab, graf
Article in English | LILACS | ID: biblio-886689

ABSTRACT

ABSTRACT This study aimed to evaluate the teratogenic and hepatotoxic potential of the usnic acid encapsulated into PLGA-microspheres. In total, 12 female Wistar rats in pregnancy were randomly distributed in the control group (n= 6) that received 1.0 mL of physiological solution and treatment group (n= 6) that received 25 mg/kg of encapsulated usnic acid by oral administration. All females were euthanized at day 20 of pregnancy and their fetuses were removed and analyzed. During the pregnancy was observed a reduction in weight gain. There was no difference in serum transaminases levels analyzed as well as any difference in liver weight in both groups. The histomorphometric analysis of the liver from the treatment group revealed an increase in number of hepatocytes and a decrease in nuclear area of these cells. Moreover, no alteration was observed in cell area of hepatocytes or number of Kupffer cells. The fetuses had an increase in total number of hepatocytes and a reduction in the amount of megakaryocytes. These results show the hepatotoxic potential of usnic acid during pregnancy. However, its toxicity can be minimized by encapsulation in microspheres.


Subject(s)
Animals , Female , Pregnancy , Polyglycolic Acid/toxicity , Ascomycota/chemistry , Benzofurans/toxicity , Lactic Acid/toxicity , Fetus/drug effects , Lichens/chemistry , Liver/drug effects , Polyglycolic Acid/chemistry , Reference Values , Abnormalities, Drug-Induced , Benzofurans/chemistry , Random Allocation , Rats, Wistar , Maternal Exposure , Lactic Acid/chemistry , Fetal Weight/drug effects , Hepatocytes/drug effects , Polylactic Acid-Polyglycolic Acid Copolymer , Liver/pathology
9.
Egyptian Journal of Hospital Medicine [The]. 2017; 67 (1): 322-329
in English | IMEMR | ID: emr-189183

ABSTRACT

Introduction: The present study was carried out to evaluate the effect of the beta-lactam antibiotic amoxicillin on the fetuses of albino mice from the morphological and skeletal points of view


Material and methods: Twenty four adult pregnant mice were used in the present study. They were allocated into 3 groups [8 mice each]. The first group served as a control and were injected intraperitoneally [i.p.] with the solvent of the drug and the second and third groups were treated with 205 and 820 mg/kg body weight of amoxicillin for 8 days [gestation days 7-14], respectively


Results: The morphological examination of the fetuses of treated groups showed growth retardation of mice fetuses as represented by the conspicuous decrease in the average body weight and body length in the two treated groups. No external malformations were recorded among fetuses maternally treated with the low dose of the drug. On the other hand, the fetuses maternally treated with the high dose showed mild external morphological malformations. In addition, the skeleton of the two treated groups exhibited incomplete ossification in most skeletal elements


Conclusion: The beta-lactam antibiotic amoxicillin had exerted mild morphological malformations and skeletal abnormalities in mice fetuses maternally treated during organogenesis period of gestation


Subject(s)
Animals, Laboratory , Fetus/drug effects , Monobactams , Mice , Skeleton/drug effects , Pregnancy, Animal
10.
Egyptian Journal of Hospital Medicine [The]. 2017; 67 (1): 366-376
in English | IMEMR | ID: emr-189189

ABSTRACT

Introduction: B-Lactam antibiotics are widely used because of their lack of toxicity in humans. However, during pregnancy, exposure of the fetus is likely to occur due to b-lactam antibiotics cross the placenta. The potential adverse effects of amoxicillin were examined in stomach of mice fetuses


Material and Methods: This study was aimed to evaluate the possible side effects produced by amoxicillin prenatal administration on the stomach of fetuses. Twenty pregnant mice were used in this study; and were divided into two groups: the first group served as a control group and injected by saline solution [the drug solvent]; the second group treated with amoxicillin dose of 205 mg/kg body weight. The treatment was daily administered interperitoneally, from the 7[th] day of gestation till the 14[th] day of gestation [GDs 7-14]. The developing 19-days old fetuses were examined histologically and ultrastructurally to determine any disorders in the stomach


Results: This study illustrated marked deleterious consequences in the gastric wall of 19 day old fetus, following the treatment with amoxicillin, ranging from marked vacuolations and erosions in the epithelial and glandular cells of the gastric mucosa to conspicuous necrosis of glandular [parietal and zymogenic] cells. The electron microscopical examination of the gastric mucosal cells of fetuses maternally treated with amoxicillin, revealed conspicuous alterations, in the cytoplasmic organelles of gastric mucosal cells [surface epithelial, peptic and parietal cells]. The cisternae of RER were dilated and fragmented. The mitochondria displayed gradual devastations


Conclusions: Therefore, the destructive impacts of amoxicillin on the stomach of mice fetuses indicated that it should be used under restricted precautions in the medical fields to protect the pregnant women from its hazardous impact


Subject(s)
Animals, Laboratory , Stomach/drug effects , Fetus/drug effects , Mice , Monobactams , Stomach/anatomy & histology , Stomach/ultrastructure
11.
Rev. bras. psiquiatr ; 37(4): 334-342, Oct.-Dec. 2015. tab
Article in English | LILACS | ID: lil-770002

ABSTRACT

Obsessive-compulsive disorder (OCD) is a relatively common psychiatric disorder in the perinatal period. However, specific pharmacological treatment approaches for patients with OCD during pregnancy have not been satisfactorily discussed in the literature. In addition, there are no randomized controlled studies on the treatment of this disorder during pregnancy. The present paper discusses the pharmacological treatment of OCD in the light of data on the safety of antipsychotics and serotonergic antidepressants during pregnancy and their efficacy in the non-perinatal period. Treatment decisions should be individualized because the risk-benefit profile of pharmacotherapy is an important issue in the treatment of pregnant women with any psychiatric diagnosis.


Subject(s)
Female , Humans , Antidepressive Agents/therapeutic use , Antipsychotic Agents/therapeutic use , Obsessive-Compulsive Disorder/drug therapy , Pregnancy Complications/drug therapy , Pregnancy/drug effects , Serotonin Uptake Inhibitors/therapeutic use , Abnormalities, Drug-Induced , Fetus/drug effects , Meta-Analysis as Topic , Pregnancy Complications/psychology , Risk Assessment , Treatment Outcome
13.
Acta cir. bras ; 29(7): 410-416, 07/2014. tab, graf
Article in English | LILACS | ID: lil-714571

ABSTRACT

PURPOSE: To evaluate the effects of exposure of enoxaparin and unfractionated heparin (UFH) in prophylactic and therapeutic doses on the fertility rates of pregnant healthy Wistar rats. METHODS: Enoxaparin and UFH were administered in prophylactic doses 1 mg/Kg/day 72 UI/Kg/day, and in therapeutic doses at 2 mg/kg/day 400UI/Kg/day. The rats were divided into five groups. The number of live and dead foetuses was quantified. The uterine horns were dissected and the presence of early and late reabsorptions (abortions) was determined. A p<0.05 was considered statistically significant. RESULTS: We did not observe statistically significant differences between groups when comparing the average weight of the foetuses and placentas, rate of female VS males, rates of pre-implantation loss (RPL), rates of efficiency implantation (REI), rates of post-implantation loss (RPIL) and rates of foetal viability (RFV). CONCLUSIONS: There was no significant effect on fertility with the use of anticoagulant drugs in pregnant healthy Wistar rats. .


Subject(s)
Animals , Female , Male , Pregnancy , Anticoagulants/administration & dosage , Enoxaparin/administration & dosage , Fertility/drug effects , Heparin/administration & dosage , Anticoagulants/adverse effects , Enoxaparin/adverse effects , Fetus/drug effects , Hemorrhage/chemically induced , Heparin/adverse effects , Placenta/drug effects , Random Allocation , Rats, Wistar , Reference Values , Time Factors , Thromboembolism/drug therapy
14.
Int. j. morphol ; 32(2): 426-431, jun. 2014. ilus
Article in English | LILACS | ID: lil-714286

ABSTRACT

Diazepam (DZ) is a benzodiazepine that belongs to the group of minor tranquilizers with myo-relaxing and anticonvulsant properties. DZ and its metabolites cross the placental barrier in human, monkey, hamster, and mouse, and accumulate in the placenta. Our aim was to investigate, through histological techniques, and semifine sections if DZ induces morphological changes in the placenta. Twenty female mice of the ICR strain were distributed randomly in two groups. One group (DZ) was treated from days 6 to 17 of gestation with a single daily subcutaneous (sc) dose of DZ of 2.7 mg/kg/ (bw); the second, control group (C) was treated with saline solution. All females (10 DZ and 10 C) were killed by decapitation. Placentas were extracted and fixed in phosphates-buffered 10% formaldehyde, pH 7.3, dehydrated, and embedded in paraffin to obtain 3 µm thick sections or fixed in 2.5% glutaraldehyde, post-fixed in 1% OsO4, embedded in epoxy resin. Histological sections were stained with hematoxylin-eosin or Weigert´s iron hematoxylin. Semifine sections were stained with toluidine blue. All sections were observed under comparative light microscopy. The DZ-group showed thinned placental barrier with multiple vacuoles. Nuclei of trophoblast cells (TCs) and trophoblast giant cells (TGCs) presented heterochromatin in coarse granules, atypically distributed in the karyolymph and conspicuous nucleoli. The cytoplasm of the TGCs was vacuolated and chromatin had a similar appearance to that observed in TCs. The total area of the placental barrier was measured in µm2/µm2; the area in the DZ group was reduced as compared with the C group (P<0.001). Alterations of TGCs could be due to an interaction of DZ with peripheral type benzodiazepine receptors involved in progesterone biosynthesis. Administration of DZ in mice alters the placental barrier and TGCs which could affect their physiology and causes teratogenic effects on the ovary and testis involved in steroid hormones biosynthesis.


El diazepam (DZ) es una benzodiazepina que forma parte de los tranquilizantes menores con propiedades miorrelajantes y anticonvulsivantes. El DZ y sus metabolitos atraviesan la barrera placentaria en el humano, mono, hámster y ratón, y se acumula en ésta. Nuestro propósito fue investigar a través de técnicas histológicas y en cortes semifinos si el DZ induce cambios morfológicos en la placenta de ratón. Hembras de ratón de la cepa ICR se distribuyeron al azar en dos grupos. Un grupo (DZ) fue tratado del día 6 al 17 de la gestación con dosis únicas diarias subcutáneas (sc) de DZ de 2.7 mg/kg (pc); el segundo grupo control (C) se trató con solución salina. Todas las hembras (10 DZ y 10 C), se sacrificaron por decapitación. Se extrajeron las placentas y se fijaron en formaldehido al 10% amortiguado con fosfatos pH 7.3, se deshidrataron y se incluyeron en parafina para obtener cortes de 3 µm, o se fijaron en glutaraldehido al 2.5%, se posfijaron en OsO4 al 1% y se embebieron en resina epóxica. Los cortes histológicos se tiñeron con hematoxilina-eosina o con hematoxilina férrica de Weigert. Los cortes semifinos se tiñeron con azul de toluidina. Todos los cortes se observaron en un microscopio óptico de comparación. El grupo DZ presentó en la barrera placentaria múltiples vacuolas. Los núcleos de las células del trofoblasto y las células trofoblásticas gigantes (TGCs) presentaron heterocromatina en grumos gruesos, distribuidos atípicamente en la cariolinfa y nucléolos conspicuos. El citoplasma de las TGCs estaba vacuolizado y la cromatina tenía una apariencia similar a la observada en las células trofoblásticas. El área total de la barrera placentaria se midió en µm2/mm2; el área en el grupo DZ era reducida en comparación del grupo C (P<0.001). Las alteraciones de las células trofoblásticas y de las TGCs podrían deberse a la interacción del DZ con los receptores benzodiazepínicos de tipo periférico involucrados en la biosíntesis de progesterona. La administración de DZ en el ratón altera la barrera placentaria y las TGCs que podrían afectar su fisiología y causar efectos teratogénicos en el ovario y el testículo involucrados en la biosíntesis de las hormonas esteroides.


Subject(s)
Animals , Male , Female , Pregnancy , Mice , Placenta/drug effects , Diazepam/toxicity , Fetus/drug effects , Muscle Relaxants, Central/toxicity , Placenta/pathology , Trophoblasts/drug effects , Mice, Inbred ICR
15.
Rev. bras. anestesiol ; 64(1): 16-21, Jan-Feb/2014. tab, graf
Article in Portuguese | LILACS | ID: lil-704244

ABSTRACT

Como todos os pacientes cirúrgicos, pacientes obstétricas também sentem estresse e ansieda de operatórios. Isso pode ser prevenido se forem passadas à paciente informações detalhadas sobre sua operação e se forem administrados medicamentos farmacológicos pré-operatórios. Devido aos efeitos depressivos dos sedativos nos neonatos, os medicamentos farmacológicos são omitidos, especialmente em pacientes obstétricas. A literatura contém poucos estudos concernentes ao uso de midazolam no pré-operatório em pacientes de secção cesariana (C/S). Nosso objetivo nesse estudo foi ajudar nossas pacientes passando por cirurgia C/S. Um grupo agendado para C/S eletiva recebeu midazolam 0,025 mg kg−1 por via intraveno sa; o outro grupo recebeu salina. A ansiedade materna foi avaliada com o uso dos escores da Amsterdam Preoperative Anxiety and Information Scale (APAIS) (Escala de Ansiedade e Informação Pré-operatória de Amsterdam), e os neonatos foram avaliados por Apgar e pelo instrumento Neonatal Neurologic and Adaptive Capacity Score (NACS) (Escore Neurológico e de Capacidade Adaptativa do Neonato). Em conclusão, os pacientes pré-medicados com midazolam 0,025 mg kg−1 medicação tiveram escores de ansiedade significativamente baixos, sem qualquer efeito adverso nos neonatos. Portanto, midazolam pode, com segurança, ser utilizado como agente de pré-medicação na cirurgia C/S.


Like all surgical patients, obstetric patients also feel operative stress and anxiety. This can be prevented by giving patients detailed information about their operation and with preoperative pharmacological medications. Because of depressive effects of sedatives on newborns, pharmacological medications are omitted, especially in obstetric patients. The literature contains few studies concerning preoperative midazolam use in Caesarian section (C/S) patients. Our aim in this study was to help patients undergoing C/S surgery. One group scheduled for elective C/S received midazolam 0.025 mg kg-1 intravenously, the other received saline. Maternal anxiety was evaluated using Amsterdam Preoperative Anxiety and Information Scale (APAIS) scores, and newborns were evaluated using Apgar and the Neonatal Neurologic and Adaptive Capacity Score (NACS). In conclusion, patients receiving midazolam 0.025 mg kg-1 as premedication had significantly low anxiety scores, without any adverse effects on the newborns. Midazolam can therefore safely be used as a premedicative agent in C/S surgery.


Como todos los pacientes quirúrgicos, las pacientes obstétricas también sienten estrés y ansiedad operatorios. Eso puede prevenirse si se le transmiten a la paciente informaciones detalladas sobre su operación y si se administran medicamentos farmacológicos preoperatorios. Debido a los efectos depresivos de los sedativos de los neonatos, los medicamentos farmacológicos se omiten, especialmente en pacientes obstétricas. La literatura contiene pocos estudios concernientes al uso de midazolam en el preoperatorio en pacientes de sección de cesárea (C/S). Nuestro objetivo en ese estudio, fue ayudar a nuestras pacientes pasando por una cirugía C/S. Un grupo con cita para C/S electiva recibió midazolam 0,025 mg.kg-1 por vía intravenosa; el otro grupo recibió salina. La ansiedad materna se evaluó con el uso de las puntuaciones de la Amsterdam Preoperative Anxiety and Information Scale (APAIS) (Escala de Ansiedad e Información Preoperatoria de Ámsterdam), y los neonatos se evaluaron por APGAR y porel instrumento Neonatal Neurologic and Adaptive Capacity Score (NACS) (Puntuación Neurológica y de Capacidad Adaptativa del Neonato). Como colofón, podemos decir que los pacientes premedicados con midazolam con 0,025 mg.kg-1 de medicación, alcanzaron puntuaciones de ansiedad significativamente bajas, sin ningún efecto adverso en los neonatos. Por tanto, el midazolam puede ser utilizado con seguridad como un agente de premedicación en la cirugía C/S.


Subject(s)
Adult , Female , Humans , Infant, Newborn , Pregnancy , Anti-Anxiety Agents/adverse effects , Fetus/drug effects , Midazolam/adverse effects , Premedication , Cesarean Section
17.
Acta cir. bras ; 27(3): 244-250, Mar. 2012. ilus, graf
Article in English | LILACS | ID: lil-617964

ABSTRACT

PURPOSE: The pathophysiology of abnormalities associated with myenteric plexus lesions remains imperfectly understood. Such abnormalities have been correlated with subocclusive intestinal conditions in children with Hirschsprung's disease, cases of chronic constipation and, postoperatively, in cases of anorectal anomalies. This study evaluated abnormalities of the myenteric plexus in fetus from female rats that received ethylenethiourea. METHODS: Female rats were exposed to ethylenethiourea on the 11th day of pregnancy (experimental group) or to 0.9 percent physiological solution (control group). Abnormalities were only found in the experimental group. The digestive tract muscle layer was analyzed morphometrically and changes to the frequencies of nerve plexus cells and interstitial cells of Cajal were evaluated, using hematoxylin-eosin, S-100 protein, neuron-specific enolase and C-Kit, respectively. RESULTS: Muscle and skeletal abnormalities were observed in 100 percent, anorectal anomalies in 86 percent, absent tail in 71 percent, short tail in 29 percent, duodenal atresia in 5 percent, esophageal atresia in 5 percent and persistent omphalomesenteric duct in 5 percent. Histopathological analysis showed a thinner muscle layer associated with lower frequencies of ganglion cells and interstitial cells of Cajal, in all gastrointestinal tract. CONCLUSION: Severe nerve plexus abnormalities associated with muscle layer atrophy were observed throughout the gastrointestinal tract in newborn rats exposed to ethylenethiourea.


OBJETIVO: As anomalias associadas a lesões dos plexos mioentéricos permanecem sem plena compreensão da sua fisiopatologia. Alterações nos plexos nervosos têm sido correlacionadas com quadros suboclusivos intestinais em crianças portadoras de doença de Hirschsprung, em constipação crônica e no pós-operatório de anomalias anorretais. Este estudo avaliou as anomalias do plexo mioentérico em fetos de ratos fêmea que ingeriram etilenotioureia (ETU). MÉTODOS: Ratos fêmea foram expostos no 11º dia de gestação a ETU 1 por cento no Grupo Experimento e a solução fisiológica 0,9 por cento no Grupo Controle. Foram observadas anomalias apenas no Grupo experimento, sendo realizada morfometria da camada muscular e avaliadas alterações da frequência celular nos gânglios do plexo mioentérico e nas células intersticiais de Cajal (CIC) utilizando hematoxilina-eosina, P S-100, Enolase Neurônio Específica e C-KIT. RESULTADOS: Foram observadas anomalias musculoesqueléticas (100 por cento), anorretais (86 por cento), ausência de cauda (71 por cento), cauda curta (29 por cento), atresia duodenal (5 por cento), atresia esofágica (5 por cento) e conduto onfalomesentérico persistente (5 por cento). A análise histopatológica mostrou adelgaçamento da camada muscular associada às alterações da frequência das células ganglionares e das CIC em todos os segmentos do trato gastrointestinal. CONCLUSÃO: Foram observadas alterações graves nos plexos nervosos associadas ao adelgaçamento da camada muscular de todo o trato gastrointestinal nos fetos expostos a ETU.


Subject(s)
Animals , Female , Rats , Abnormalities, Drug-Induced/pathology , Digestive System Abnormalities/chemically induced , Ethylenethiourea/toxicity , Muscular Atrophy/chemically induced , Myenteric Plexus/abnormalities , Pregnancy/drug effects , Prenatal Exposure Delayed Effects/chemically induced , Animals, Newborn , Abdominal Muscles/innervation , Disease Models, Animal , Digestive System Abnormalities/classification , Digestive System Abnormalities/pathology , Fetus/drug effects , Ganglia/cytology , Interstitial Cells of Cajal/cytology , Muscular Atrophy/pathology , Prenatal Exposure Delayed Effects/pathology , Random Allocation , Rats, Wistar , Statistics, Nonparametric , Staining and Labeling/methods
18.
Rev. bras. ginecol. obstet ; 34(1): 22-27, jan. 2012. tab
Article in Portuguese | LILACS | ID: lil-614795

ABSTRACT

OBJETIVO: Avaliar os efeitos da ipriflavona durante a fetogênese, já que não foram encontrados estudos visando avaliar seu efeito durante este período. MÉTODOS: Foram utilizadas 60 ratas prenhes, distribuídas aleatoriamente em quatro grupos (n=15). G-controle (1 mL de água destilada) e três grupos tratados com ipriflavona, via intragástrica, do 16º ao 20º dia pós-coito (PC): G-300 (300 mg/kg), G-1500 (1.500 mg/kg) e G-3000 (3.000 mg/kg). Os animais foram pesados e sacrificados no 21º dia por exsanguinação total sob anestesia (xilazina (10 mg/kg) e quetamina (90 mg/kg) via intraperitoneal. Foi realizado hemograma completo e dosagens séricas de colesterol, triglicérides, AST, ALT, ureia, creatinina e glicose das ratas prenhes. Após laparotomia foram removidos e pesados fígado, rim, suprarrenais, baço e ovários; os fetos e placentas foram pesados obtendo-se o peso médio das ninhadas. Quatro fetos (dois machos e duas fêmeas) por mãe foram aleatoriamente designados para obter-se o comprimento e peso de cérebro, fígado, rins e pulmões. Para a análise estatística utilizou-se o teste ANOVA seguido do teste de Dunnet; para dados não homocedásticos e sem distribuição normal, foi usado o teste de Kruskal-Wallis, seguido de Mann-Whitney; as proporções foram analisadas pelo teste do χ² (p<0,05) RESULTADOS: Níveis de triglicérides (mg/dL): G-Controle (138,8±21,8); G-300 (211,2±63,9); G-1500 (251,5±65,2); G-3000 (217,7±49,6); p<0.05. Peso corporal dos fetos (g): G-Controle (machos 3,3±0,3; fêmeas 3,1±0,3); G-300 (machos 3,4±0,2; fêmeas 3,1±0,4); G-1500 (machos 3,5±0,3; fêmeas 3,2±0,3); G-3000 (machos 3,4±0,5; fêmeas 3,1±0,4). CONCLUSÃO: A ipriflavona não causou toxicidade materna, mas elevou níveis de triglicérides e reduziu o hematócrito em doses elevadas, o tamanho, peso corporal e de órgãos fetais não foram alterados. Não foram observadas malformações externas nem mortes fetais.


PURPOSE: Evaluate the effects of ipriflavone during fetogenesis, since no studies have been conducted to assess its effect during this period. METHODS: 60 pregnant rats were divided randomly into four groups (n=15). G-control (1 mL of distilled water) and three groups treated intragastrically with ipriflavone from the 16th to the 20th post coitus (PC) day: G-300 (300 mg/kg), G-1,500 (1,500 mg/kg) and G-3,000 (3,000 mg/kg). The animals were weighed, anaesthetized intraperitoneally with xylazine and ketamine at doses of 180 mg/kg and 10 mg/kg, respectively, and sacrificed by total exsanguination on the 21st day. A complete blood count was performed and serum cholesterol, triglycerides, AST, ALT, urea, creatinine, and glucose were determined in pregnant rats. After laparotomy, the liver, kidneys, adrenals, spleen and ovaries were removed and weighed; fetuses and placentas were also weighed to obtain the average weight of the litters. Four fetuses (two males and two females) were chosen at random for the determination of the length and weight of brain, liver, kidneys and lungs. Statistical analysis: ANOVA followed by Dunnett's test. For raw data without normal distribution and homoscedasticity, we used the Kruskal-Wallis test followed by the Mann-Whitney test. Proportions were analyzed by the χ² test (p<0.05). RESULTS: Triglyceride levels (mg/dL) were: Control-G (138.8±21.8), G-300 (211.2±63.9) G-1,500 (251.5±65.2) G-3,000 (217.7±49.6); p<0.05. The body weight of fetuses (g) was: G-Control (male 3.3±0.3; female 3.1±0.3), G-300 (male 3.4±0.2; female 3.1±0.4), G-1,500 (male 3.5±0.3; female 3.2±0.3), G-3,000 (male 3.4±0.5; female 3.1±0.4). CONCLUSION: Ipriflavone did not cause maternal toxicity, but increased triglyceride levels and reduced hematocrit at higher doses. The body and organ weights of the fetuses did not change with dam treatment. There were no external malformations or fetal deaths.


Subject(s)
Animals , Female , Male , Pregnancy , Rats , Fetus/drug effects , Isoflavones/pharmacology , Rats, Wistar
19.
Rev. bras. ginecol. obstet ; 32(11): 556-562, nov. 2010. ilus, tab
Article in Portuguese | LILACS | ID: lil-572642

ABSTRACT

OBJETIVO: avaliar os efeitos da administração da associação zidovudina-lamivudina-ritonavir nos fígados e rins de ratas prenhes e seus conceptos do ponto de vista morfológico e fisiológico. MÉTODOS: 40 ratas albinas prenhes foram aleatoriamente divididas em 4 grupos: 1 controle (Ctrl: controle de veículo) e 3 experimentais (Exp1x, Exp3x e Exp9x). Estes últimos foram tratados por solução oral de zidovudina/lamivudina/ritonavir (Exp1x: 10/5/20 mg/kg; Exp3x: 30/15/60 mg/kg; Exp9x: 90/45/180 mg/kg). As drogas e o veículo foram administrados por gavagem, desde o 1º até o 20º dia de prenhez. No último dia do experimento, todos os animais foram anestesiados e sangue foi retirado da cavidade cardíaca para avaliação sérica das enzimas aspartato aminotransferase (AST) e alanina aminotransferase (ALT), por método calorimétrico, bem como da ureia, determinada por método cinético-enzimático, e creatinina, por método cinético-colorimétrico. Em seguida, fragmentos dos fígados e rins maternos e fetais foram coletados, fixados em formol a 10 por cento e processados segundo os métodos histológicos para inclusão em parafina. Cortes com 5 µm de espessura foram corados pela hematoxilina-eosina (HE) e analisados por microscopia de luz. Na leitura das lâminas, considerou-se o padrão de normalidade para fígado e rins, tais como: hepatócitos, espaço porta íntegros e veias hepáticas bem definidas. Nos rins, a presença de corpúsculos renais, túbulos contorcidos e alças de Henle típicos. Nos fígados fetais considerou-se, ainda, a morfologia das células da linhagem eritrocitária nas diferentes fases do desenvolvimento, bem como os megacariócitos. Quando houve alteração da coloração padrão estabelecida para as estruturas hepáticas e renais, alteração na morfologia de núcleos, rompimento de limites de alguma organela citoplasmática, presença de congestão vascular, tudo isso foi entendido como provavelmente provocado pelas drogas em sua(s) dose(s) de aplicação. A avaliação estatística foi realizada por análise de variância (ANOVA), completada pelo teste de Tukey-Kramer (p<0,05). RESULTADOS: os fígados maternos dos grupos Ctrl, Exp1x e Exp3x mostraram hepatócitos típicos, espaço porta íntegros e veias hepáticas com aspecto normal. No fígado materno do grupo Exp9x, foram encontrados hepatócitos com sinais de atrofia e apoptose (eosinofilia citoplasmática e núcleos picnóticos). Além disso, identificou-se vasodilatação dos capilares sinusoides (congestão). Os rins maternos dos grupos Ctrl e Exp1x apresentaram-se normais, com corpúsculos renais, túbulos contorcidos e alças de Henle típicos. Já nos grupos Exp3x e Exp9x, foram encontrados congestão vascular, glomérulos pequenos ricos em células contendo núcleos hipercromáticos, sendo mais intensos no Exp9x. Com relação aos fígados e rins fetais, não foram observadas alterações morfológicas ou fisiológicas nos grupos estudados. Encontrou-se aumento significante nos níveis da AST (305,70±55,80; p<0,05) e da creatinina (0,50±0,09; p<0,05) no grupo Exp9x. CONCLUSÕES: nossos resultados evidenciam que a administração da associação zidovudina/lamivudina/ritonavir a ratas prenhes em altas doses causa alterações morfológicas e funcionais nos fígados e rins maternos. Não houve alterações nem morfológicas nem fisiológicas nos fígados e rins fetais.


PURPOSE: to evaluate the effect of administration of three different doses of the zidovudine/lamivudine/ritonavir combination on the liver and kidneys of pregnant rats and their concepts from a morphological and physiological standpoint. METHODS: 40 pregnant EPM-1 Wistar rats were randomly divided into 4 groups: 1 control (Ctrl: drug vehicle control, n=10) and 3 experimental groups: Exp1x, Exp3x and Exp9x. An oral solution of the zidovudine/lamivudine/ritonavir combination was administered to the experimental groups from the day 0 to day 20 of pregnancy: Exp1x=10/5/20 mg/kg; Exp3x=30/15/60 mg/kg; Exp9x=90/45/180 mg/kg. On the 20th pregnancy day the rats were anesthetized and blood was taken directly from the ventricular chambers for further biochemical determinations: aspartate-(AST) and alanine-(ALT) aminotransferases (Calorimetric method), urea nitrogen (BUN) by an enzymatic-kinetic method, and creatinine by a kinetic-calorimetric method. Maternal and fetal liver and kidney samples were taken, fixed in 10 percent formaldehyde and processed histologically for paraffin embedding. Five µm-thick fragments of maternal and fetal livers and kidneys were stained with hematoxilyn-eosin, being analyzed by light microscopy. To interpret the results, the well-known pattern of normality for livers and kidneys was considered on the basis of the following structures: hepatocytes, portal structure, hepatic veins, renal corpuscles, renal tubules and loop of Henle. Regarding the fetal livers, we also considered the erythrocytes in their different stages of development as well as the megacariocytes. If there was a change in the established staining pattern for liver and kidney structures, changes in nuclear morphology, rupture of some cytoplasmic organelles, and presence of vascular congestion, this was considered to be due to the drug doses. Results were submitted to analysis of variance (ANOVA) and to the Tukey-Kramer multiple comparisons test (p<0.05). RESULTS: no morphological changes were observed in the maternal livers of the Ctrl, Exp1x and Exp3x groups. In the maternal liver of the Exp9x group, hepatocytes showed signs of atrophy and apoptosis (eosinophilic cytoplasm and pycnotic nuclei) and marked sinusoid capillary vasodilation (congestion) was observed. The maternal kidneys of the Ctrl and Exp1x groups were normal, with renal corpuscles, convoluted tubules and typical loops of Henle. In contrast, the Exp3x and Exp9x groups showed vascular congestion and small glomeruli rich in cells containing hyperchromatic nuclei which were more intense in Exp9x. Regarding the fetal organs, no morphological or physiological changes were observed. A significant increase of AST (305.70±55.80, p<0.05) and creatinine (0.50±0.09, p<0.05) was observed in group Exp9x. CONCLUSIONS: our results show that the administration of the zidovudine, lamivudine and ritonavir combination to pregnant rats at high doses caused morphological and physiological changes in the maternal liver and kidneys. On the other hand, there were no changes in fetal organs.


Subject(s)
Animals , Female , Pregnancy , Rats , Anti-HIV Agents/pharmacology , Fetus/anatomy & histology , Fetus/drug effects , Kidney/anatomy & histology , Kidney/drug effects , Lamivudine/pharmacology , Liver/anatomy & histology , Liver/drug effects , Ritonavir/pharmacology , Zidovudine/pharmacology , Fetus/pathology , Fetus/physiology , Fetus/physiopathology , Kidney/pathology , Kidney/physiology , Kidney/physiopathology , Liver/pathology , Liver/physiology , Liver/physiopathology , Rats, Wistar
20.
Rev. bras. psiquiatr ; 32(2): 152-158, jun. 2010. tab
Article in English | LILACS | ID: lil-554008

ABSTRACT

OBJECTIVE: To evaluate morphological alterations in rat fetuses treated with fluoxetine and imipramine during the "critical" period of gestation. METHOD: Fifteen female rats were separated into three groups (n = 5) and treated with 10 mg/kg/day of test substances on the ninth, tenth and eleventh day of pregnancy: G1, fluoxetine; G2, imipramine hydrochloride; G3 (control), saline. On day 21, cesarean sections were performed to release the fetuses, whose bodies were weighed and macroscopically analyzed. The placenta was also weighed. The fetuses were then fixed and their encephala removed and weighed. Sections of the frontal lobe were taken for histological neuron counting. RESULTS: G1 and G2 showed the highest fetal body weight. Placental weight showed statistical differences (p < 0.01): G1 weighed more than G2 and G3. Otherwise, G2 exhibited the highest encephalon weight, statistically differing from G3 (control) and fluoxetine-treated G1 (p < 0.01). However, G1 did not statistically (p > 0.01) differ from the control group. G3 showed the highest number of neurons per area when compared to G1 and G2 (p < 0.01). CONCLUSION: The use of antidepressants in rats caused an increase in fetal weight and a decrease in the number of fetal frontal lobe neurons, thus suggesting that the use of antidepressants by pregnant women can induce depression in fetuses due to alterations in their neural development.


OBJETIVO: Avaliar as possíveis alterações ocorridas em nível macroscópico e microscópico de fetos de ratas submetidas ao tratamento com fluoxetina e imipramina durante o período "crítico" da gestação. MÉTODO: Quinze ratas, posteriormente ao acasalamento, foram divididas em três grupos experimentais (n = 5): G1, tratadas com 10mg/kg/dia de fluoxetina; G2, tratadas com 10mg/kg/dia de cloridrato de imipramina, e G3 (controle), tratadas com 10mg/kg/dia de solução fisiológica a 0,9 por cento, no 9º, 10º e 11º dias de prenhez das ratas. Posteriormente à cesária, no 21º dia de prenhez, analisou-se macroscopicamente o peso fetal e placentário. Os fetos foram fixados e houve a remoção do encéfalo para pesagem e preparação das lâminas do tecido neuronal para contagem de neurônios do lobo frontal. RESULTADOS: O G1 e G2 apresentaram maior peso fetal. O G1 apresentou maior peso placentário, diferindo do G2 e G3 (p < 0,01). De forma diferente, o G2 possuiu maior peso encefálico, diferindo do G3 e G1 (p < 0,01). G1 não diferiu estatisticamente do grupo controle (p > 0,01). O G3 exibiu maior número de neurônios, por área, do lobo frontal em relação a G1 e G2 (p < 0,01). CONCLUSÃO: A adoção dos antidepressivos causou, nos fetos, aumento de peso e redução da contagem de neurônios do lobo frontal, sugerindo que a indicação de antidepressivos às gestantes pode induzir a depressão nos fetos por alterações em seu neurodesenvolvimento.


Subject(s)
Animals , Female , Pregnancy , Rats , Antidepressive Agents/pharmacology , Brain/drug effects , Dopamine Uptake Inhibitors/pharmacology , Fetus/drug effects , Fluoxetine/pharmacology , Imipramine/pharmacology , Antidepressive Agents/therapeutic use , Brain/embryology , Fetal Weight/drug effects , Fetus/anatomy & histology , Placenta/drug effects , Rats, Wistar
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