A fertilização in vitro tem sido associada com um aumento na incidência das hipospádias, e alguns hormônios esteróides usados em seus protocolos têm sido implicados neste processo. Para testar essas hipóteses em um modelo animal, descrevemos neste trabalho as alterações morfológicas ocorridas no tubérculo genital de camundongos, expostos à progesterona durante a vida intrauterina. Foi administrado acetato de medroxiprogesterona por via subcutânea no período pré-natal em animais normais e animais desprovidos de receptores androgênicos (Tfm). A progesterona induziu a formação de hipospádia nos animais do sexo masculino, virilização nos do sexo feminino e não causou alterações nos animais Tfm / In vitro fertilization (IVF) has been associated with an increase incidence of hypospadias. IVF protocols require the maternal use of progesterone which may be a factor in causing hypospadias. To test these hypotheses in an animal model, we describe the effects of maternal progesterone exposure on genital development in mice. Medroxyprogesterone acetate (MPA) was administered by subcutaneous injection during the pre-natal period to wild type mice and animals knockout to androgen receptors (Tfm mice). Progesterone caused hypospadias in male mice fetuses, a virilizing effect in the female mice genitalia and didn't have any effect in Tfm animals

A minoria dos pacientes em processo de remodelamento pulmonar por bronquiolite obliterante (BO) responde a corticosteróides. Nos propusemos assim, a avaliar a importância da tolerância gerada pela imunização via nasal pelo colágeno tipo V (ctV) como uma opção no tratamento da BO. Através da análise morfométrica, mensuramos as dimensões, a densidade de colágeno e infiltrado celular no eixo pré-acinar visando o entendimento na patogênese da BO. Aplicamos essa metodologia a três protocolos: primeiro, o estabelecimento do modelo da BO em camundongos BALB/c. Segundo, a tolerância preventiva a BO. Terceiro, comparar os tratamentos prednisona vs tolerância após a BO já estabelecida. Oito semanas após uma única instilação de HNO3-nasal, as mudanças pulmonares foram caracterizadas pela distorção do lúmen, perda da barreira epitelial, redução ou total obliteração do lúmen do bronquíolo terminal e aumento do espessamento da parede. Modelo da BO: A densidade do infiltrado celular total mostrou valores significantes quando comparados os pulmões BO vs salina e controle (P = 0,001 para ambos), com maior evidência a densidade macrófagos nos pulmões controle vs BO e salina (P = 0,01 e P = 0,04, respectivamente). Tolerância preventiva: A densidade de CD3+ mostrou diminuição significante quando comparado ao estágio intermediário da doença nos pulmões BO vs BO+ctV e controle (P = 0,001 e P = 0,002, respectivamente). Houve também diminuição estatística da densidade de células CD20+ quando comparados os pulmões BO vs ctv+BO, BO+ctV, e controle (P = 0,008, P = 0,004 e P = 0,001). Prednisona vs tolerância: A densidade total de células diminuiu drasticamente quando comparados os pulmões BO vs BO+ctV e controle (P = 0,003 e P = 0,001, respectivamente). As células CD3+ mostraram diminuição quando comparados os pulmões BO vs BO+pr, BO+ctV e controle (P = 0,03, P = 0,03 e P = 0,05, respectivamente). Houve também diminuição das células CD20+ e CD4+ quando comparados os pulmões BO vs BO+ctV e controle (P = 0, 006 e P = 0,004, respectivamente) e (P = 0,001 para ambos). A histoarquitetura e a densidade de células dos pulmões BO+ctV se assemelharam ao pulmões controle. A tolerância pelo ctV comparada com o prednisona, mostrou marcante diminuição da deposição de colágeno e infiltrado celular no eixo pré-acinar. Nossos resultados indicam que o ctV pode atuar como um supressor da resposta imune. Concluímos, portanto, que a morfometria foi um método apropriado para relatar o espectro de mudanças histológicas no modelo de BO proposto. / A minority of patients with remodeling process of lungs following bronquiolite obliterante (BO) responds to corticosteroids. So, we sought to validate the importance of type V collagen (tVc) tolerance from immunization as option in BO model treatment. Througt of morphometric analyses, we have mensured for the dimensions, the collagen and cell infiltration density on pre-acinar axis, target the understand of BO pathogenesis. We applied for tree protocols: First, the establishment of BO model on BALB/c mice. Second, preventive tolerance to BO. Third, prednisone treatment vs tolerance, after BO established. Eight weeks after a single HNO3- nasal instillation, lung changes were characterized by lumen distortion, epithelial layer folding, reduction or total obliteration of terminal bronchiole lumen, and wall thickness increase. The morphological changes coincide with the measurement difference in the study for the tree protocols established. BO model: The total density of immune cells showed stasticaly significance when was compared BO vs saline and control lungs (P = 0.001 for both), more evidence to macrophage on control vs BO and saline lungs (P = 0.01 and P = 0.04, respectevely). Preventive tolerance: The CD3+ density showed a decreased statiscaly significance in lower BO vs BO+tVC and control lungs (P = 0.001 and P = 0.002, respectevely). Also the CD20+ density was decreased when was compared BO vs tVc+BO, BO+tVc and control (P = 0.008, P = 0.004 and P = 0.001). Prednisone vs tolerance: The total density of immune cells was decreased drastically when was compared BO vs BO+tVc and control lungs (P = 0.003 and P = 0.001, respetevely). These cells were CD3+ when was compared BO vs BO+pr, BO+tVc and control lungs (P = 0.03, P = 0.03 and P = 0.05, respectevely); Also CD20+ cells and CD4+ were decreased when was compared BO vs BO+tVc and conmtrol lungs (P = 0.006 and P = 0.004, respectevely) and (P = 0.001, for both). The histoarchiteture from BO+tVc and immune cells as simmilar to control lungs. The tolerance with tVc when was compared to prednisona, showed us a decreased of collagen and immune cell density in pre-acinar axis. Our results indicating that tVc may acts as a supressor in inflammatory process in bronchiolar remodeling. We conclued that method morphometric was effective for related us the spectrum of histologic changes in BO model propose. Ours results indicating that induction of tVc acts in suppression of the immune response. We conclude that morphometric analise was a aproprieated for related the spectrum of histologic changes for propose BO model.

Camundongos Balb/c receberam instilação intranasal de 50 l de papaína (20 mg/ml) ou solução salina. A instilação de papaína resultou em uma diminuição significativa de Ers (p=<0,001), Gtis (p=0,030) e Htis (p=0,012). Houve um aumento de k, uma constante medida na curva PV. Não observamos diferença estatística nos parâmetros R e E na mecânica do parênquima pulmonar quando comparamos os diferentes grupos. Os camundongos instilados com papaína apresentaram valores aumentados do diâmetro alveolar médio no tecido pulmonar e aumento na proporção de fibras de colágeno, comparados aos que receberam salina (p<0,001 e p=0,004, respectivamente). As medidas in vivo detectaram alterações pulmonares em camundongos enfisematosos. Entretanto, as medidas in vitro, na mecânica do parênquima pulmonar, não foram capazes de detectar essas alterações. / Male Balb/c mice received a nasal drop of 50 l of papain (20 mg/ml) or normal saline. After 28 days of instillation, lungs from papain-treated mice showed a significant decrease in mean values of Ers (P=<0,001),Gtis (P=0.030) and Htis (P=0.012). There was an increase in mean values of k, a constant measured in P-V curve. We did not observe a significant difference between the groups in R and E in lung tissue strips. Papain instillation presented greater values of mean linear intercept and increase in the density of collagen fibers in alveolar septa in pulmonary tissue than saline-treated mice (P<0.001 and P=0.004, respectively). We conclude that in vivo measurements of pulmonary mechanics detected pulmonary emphysematous changes in mice. In contrast, in vitro measurements in lung strips with oscillatory mechanics did not detect these changes

Os modelos experimentais de falência do ventrículo direito (VD) descritos são de difícil execução, por envolverem procedimentos cirúrgicos complexos e dispendiosos, com alta mortalidade e baixa reprodutividade. Também são raros aqueles que promovem falência ventricular exclusiva do ventrículo direito. Com o objetivo de simular a situação clínica de falência ventricular exclusiva do VD, desenvolvemos um modelo experimental de falência crônica isolada do VD, feito através da injeção de etanol intramiocárdico. A disfunção do VD foi induzida em treze cães adultos, através de múltiplas injeções de etanol a 96% (dose total 1ml/kg), na via de entrada e na porção trabecular do VD. Foram analisados parâmetros hemodinâmicos, metabólicos e ecocardiográficos, em condições basais e após indução da falência. Os animais foram mantidos vivos por um período de 14 dias, após o qual foram reoperados e mortos para análise morfológica dos corações. As pressões foram aferidas na artéria femoral, átrio esquerdo (AE), átrio direito (AD), tronco pulmonar (TP) e VD. O fluxo sanguíneo foi medido na aorta e no tronco pulmonar. Na primeira operação, os dados hemodinâmicos foram registrados antes e imediatamente após a indução da falência do VD. Estes parâmetros também foram coletados na reoperação (14 dias pós-indução da falência). Amostras de sangue arterial e venoso foram colhidas simultaneamente ao registro dos parâmetros hemodinâmicos para avaliação dos gases sanguíneos e dosagem de lactato. Foram feitas avaliações ecocardiográficas no pré-operatório, no sexto e no 130 dia pós-operatório (PO). Houve uma mortalidade de 15,4% (2/13). Observou-se uma queda significativa no débito cardíaco pulmonar após a indução da falência e na reoperação (14º PO), quando comparado aos valores medidos no momento basal (p=0,002). Esta queda do desempenho ventricular direito ocasionou um aumento nos valores do lactato venoso, quando comparados os valores basais contra aqueles do pós infusão de etanol (p=0,0001) e com os da reoperação (p=0,0003). Os dados ecocardiográficos revelaram um aumento no volume diastólico do VD, quando comparados os dados basais com aqueles da primeira semana de seguimento (p=0,0001) e com aqueles medidos duas semanas após a indução da falência (p=0,0084). Houve uma queda significativa da fração de ejeção do VD na primeira e segunda semanas em comparação aos valores basais (p=0,0001). A avaliação microscópica feita a partir de amostras retiradas do VD revelou infartos transmurais, com características histológicas compatíveis com infarto de duas semanas de evolução. A injeção de etanol intramiocárdio permitiu a criação de um modelo simples, econômico e reprodutível de falência crônica isolada do VD. A avaliação dos dados hemodinâmicos, ecocardiográficos e bioquímicos medidos nos diferentes momentos do experimento é compatível com a indução de falência grave do VD. Este modelo pode ser útil no estudo da fisiopatologia da falência isolada do VD, bem como na avaliação de assistência ventricular. / Isolated chronic right ventricle (RV) dysfunction is difficult to achieve in experimental models, and sometimes very expensive. Some models require complex surgical procedures, with a high mortality rate and low reproducibility. In order to simulate the clinical status of RV failure, we have developed an experimental model of chronic RV failure by injecting local intramyocardial ethanol 96%. A severe RV dysfunction was induced in 13 mongrel dogs by means of multiple intramyocardial injections of ethanol 96% (total dose of 1ml/kg), in the inlet and trabecular portions of the RV. The hemodynamics, metabolic and ecocardiografic parameters were evaluated at baseline condition and after RV failure. The animals were followed for a 14-day period. After that, they were reoperated for pressure measurements, taken from femoral artery, left atrium (LA), right atrium (RA), RV and main pulmonary artery (PA). Blood flow was measured in the aorta (AO) and PA. Metabolic parameters were assessed simultaneously to pressure measurements, with arterial and venous blood samples withdrawn for gas and lactate analysis, and then, they were killed for morphological evaluation of the heart. All the animals were submitted to echocardiographic evaluation before the first operation, on sixth and on de 13th postoperative day. The mortality rate was 15,4% (2/13). There was a significant decrease in the pulmonary blood flow after RV failure induction (p=0,0018), as well as in the reoperation (p=0,002), as compared to baseline. This decrease in RV performance caused an increase in the venous lactate level, when baseline values are compared with pos infarction values (p=0,001) and reoperation (p=0003). The echocardiografic findings revealed an increased RV diastolic volume on the 6th (p=0,0001) and 13th postoperative day (p=0,0084), as compared to baseline values. Conversely, there was a significant decrease in the RV ejection fraction on the 6th and 13th postoperative day, when compared with baseline values (p=0,0001). Microscopic evaluation of RV samples showed transmural infarctions with histological characteristics aged of two weeks. Intra myocardial ethanol injection has allowed the creation of a simple, inexpensive and reproducible model of chronic RV failure. The hemodynamic, metabolic and echocardiographic parameters assessed in different moments of the protocol are compatible with severe RV failure. It may be useful for RV physiology studies of isolated right sided heart failure, as well as in the assessment of ventricular assist devices.

No description available.

The relative risk of major gastrointestinal bleeding (GIB) among different direct oral anticoagulants (DOACs) is debatable. Randomized controlled trials (RCTs) comparing DOACs with each other are lacking. We performed network meta-analysis to assess whether the risk of major GIB differs based on type and dose of DOAC. Literature search of PubMed, EMBASE and Cochrane databases from inception to August 2019, limited to English publications, was conducted to identify RCTs comparing DOACs with warfarin or enoxaparin for any indication. Primary outcome of interest was major GIB risk. We used frequentist network meta-analysis through the random-effects model to compare DOACs with each other and DOACs by dose to isolate the impact on major GIB. Twenty-eight RCTs, including 139 587 patients receiving six anticoagulants, were selected. The risk of major GIB for DOACs was equal to warfarin. Comparison of DOACs with each other did not show risk differences. After accounting for dose, rivaroxaban 20 mg, dabigatran 300 mg and edoxaban 60 mg daily had 47, 40 and 22% higher rates of major GIB versus warfarin, respectively. Apixaban 5 mg twice daily had lower major GIB compared to dabigatran 300 mg (OR, 0.63; 95% CI, 0.44-0.88) and rivaroxaban 20 mg (OR, 0.60; 95% CI, 0.43-0.83) daily. Heterogeneity was low, and the model was consistent without publication bias (Egger's test: P = 0.079). All RCTs were high-quality with low risk of bias. DOACs at standard dose, except apixaban, had a higher risk of major GIB compared to warfarin. Apixaban had a lower rate of major GIB compared to dabigatran and rivaroxaban.

Discussion of the hematologic complications of vaccination for severe acute respiratory syndrome coronavirus-2 (COVID-19) has primarily focused on the development of vaccine-associated immune thrombosis with thrombocytopenia (VITT). Other hematologic complications are uncommon. We report the case of a patient who developed immunoglobulin G (IgG)-mediated autoimmune hemolytic anemia (AIHA) after the Moderna COVID-19 messenger ribonucleic acid (mRNA) vaccine.

No description available.

<p>U eksperimantalnom postupku disertacije mi&scaron;evi NMRI soja su tretirani infuzom biljke Aristolochia clematitis. Sasu&scaron;eni listovi, grane i plodovi biljke potopljeni su u ključalu vodu i ostavljeni 3-5 sati da stoje, a potom su profiltrirani kroz filter papir. Pravljen je rastvor biljke/vode od 10g/ 1000ml (1%), 20g/ 1000ml (2%) i 40g/ 1000ml (4%). Različite koncentracije infuza su date mi&scaron;evima da piju u neograničenoj količini u periodu od 7 nedelja. Tako su formirane tri ispitne grupe, prva koja je primala 1% infuz, druga 2% infuz i treća 4% infuz i kontrolna grupa koja je dobijala samo vodu da pije. U svakoj grupi je bilo 20 životinja. Tako je razvijen animalni model hronične toksičnosti. Na kraju eksperimenta je urađena patohistolo&scaron;ka analiza bubrega, makroskopski pregled organa i merenje diureze tokom trajanja eksperimenta. Urađena je kompletna analiza urina koja podrazumeva utvrđivanje: boje, izgleda, pH, specifične težine, proteina i sedimenta urina. Analize urina ponavljane su na svakih 7 dana u toku 7 nedelja istraživanja. Na kraju eksperimenta urađena je analiza biohemijskih parametara (glukoza, urea, kreatinin, mokraćna kiselina, ukupni bilirubin, direktni bilirubin, ukupni tj. totalni proteini, natrijum i kalijum) i analiza kompletne krvne slike. Utvrđeno je da je Aristolochia clematitis izrazito nefrotoksična biljka. Utvrđene su patohistolo&scaron;ke promene tubula i intersitcijuma NMRI mi&scaron;a, koje su bile najveće u ispitnoj grupi koja je primala najaču dozu. Ustanovljene&nbsp; patohistolo&scaron;ke promene su slične opisanim patohistolo&scaron;kim promenama tubulointersticijuma bolesnika obolelih od Balkanske endemske nefropatije. Nije ustanovljeno postojanja karcinoma gornjeg urotrakta. Makroskopskim pregledom prilikom obdukcije eksperimentalnih životinja nisu ustanovljene značajnije promene bubrega. Do&scaron;lo je prvo do izrazitog porasta diureze u prvoj, odnosno drugoj nedelji praćenja, kod druge i treće eksperimentalne grupe, da bi nakon 7 nedelja istaživanja diureza u svim ispitnim grupama bila manja od kontrolne grupe. Postoji porast ureje na kraju istraživanja, koji je dvostruko veći u trećoj eksperimentalnoj grupi u odnosu na kontrolnu. Postoji izrazit pad mokraćne kiseline na kraju istraživanja kod eksperimentalne grupe 3. Postoji izrazit pad granulocita u leukocitarnoj formuli u svim ispitnim grupama, a najveći je u trećoj ispitnoj grupi. Kako je do&scaron;lo do pada relativnih vrednosti granulocita, tako je do&scaron;lo do porasta relativnih vrednosti limfocita u prvoj i drugoj ispitnoj grupi. U trećoj ispitnoj grupi je pad granulocita praćen izrazito velikim povećanjem relativnog broja bazofilnih granulocita. Postoji značajan pad specifične težine urina na kraju istraživanja u drugoj i trećoj eksperimentalnoj grupi. Proteinurija je bila čest nalaz svim eksperimentalnim grupama, dok je bila odsutna ili samo u tragu u kontrolnoj grupi. Na kraju eksperimenta je utvrđen znatni porast broja kristala fosfata u eksperimentalnim grupama. Cilindri su se pojavljivali samo u nalazu urina u trećoj ispitnoj grupi. Najveći broj promena urina je utvrđen u trećoj eksperimentlanoj grupi.</p> / <p>In the experimental procedure of dissertation, NMRI strain mice were treated with infusion of plants Aristolochia clematitis. Dried leaves, branches and fruit plants are submerged in boiling water and left to stand for 3-5 hours, and then filtered through filter paper. It was made a solution of the plant / water of 10g / 1000ml (1%), 20g / 1000ml (2%) and 40g / 1000ml (4%). Different concentrations of infusions were given to mice to drink an unlimited amount for a period of 7 weeks. So we formed the three test groups, the first who received 1% infusion, the second received 2% infusion and third received 4% infusion and a control group that received only water to drink. In each group there were 20 animals. Thus, developed an animal model of chronic toxicity. At the end of the experiment was performed histopathological analysis of kidneys, macroscopic examination of organs and measuring urine output during the experiment. We performed a complete analysis of urine, which is the determination of: color, appearance, pH, specific gravity, protein and urine sediment. Urinalysis were repeated every 7 days during the 7 weeks of the study. At the end of the experiment were analyzed for biochemical parameters (glucose, urea, creatinine, uric acid, total bilirubin, direct bilirubin, total proteins, sodium and potassium) and analysis of the complete blood count. It has been found that Aristolochia clematitis is extremely nephrotoxic plant. Identified histopathological changes of tubules and interstitium of NMRI mouse, which were the biggest in the test group receiving biggest dose. Established histopathological changes are similar to those described by pathological changes of tubulointerstitial injury of patients with Balkan endemic nephropathy. Not established the existence of cancer of the upper urinary tract. Macroscopic examination at autopsy of experimental animals, did not determine significant changes in the kidneys. There is first an enormous increase in diuresis in the first and second week of follow-up, in the second and third experimental groups retrospectively, that after 7 weeks of research, diuresis in all test groups was lower than the control group. There is an increase of urea at the end of the research, which is twice higher in the third experimental group compared to the control. There is a marked decrease in uric acid at the end of the research in the experimental group 3. There is a marked decrease in granulocytes in the leukocyte formula in all test groups, and the highest in the third test group. As the decline in the relative values of granulocytes, so there has been a rise in the relative values of lymphocite in the first and second test group. In the third test group, granulocyte drop was accompanied by a extremely large increase in the relative number of basophils. There is a significant drop in specific gravity of urine at the end of the research in the second and third experimental group. Proteinuria is a common finding to all experimental groups, while it was absent or only in traces in the control group. At the end of the experiment was determined to increase significantly the number of phosphate crystals in the experimental groups. The cylinders have appeared only in the urine in the third test group. The greatest number of changes in the urine is determined in the third experimental group.</p>

A síndrome de hiperestímulo ovariano (SHO) pode ocorrer de forma espontânea na gestação ou durante indução da ovulação para fertilização in vitro. Com o objetivo de identificar fatores clínicos e hormonais de risco para a SHO iatrogênica e analisar o papel das variantes alélicas do FSHR na sua etiologia, estudamos 29 pacientes com SHO iatrogênica moderada e grave. Idade < 33,5 anos, FSH basal < 5,2 UI/L e resposta de estradiol > 1757 pg/mL durante a estimulação ovariana atuaram como preditores independentes do risco de desenvolvimento da SHO iatrogênica, sendo a associação dos três fatores capaz de predizer a síndrome com acurácia de 78%. Não foram encontradas mutações nas 29 pacientes com SHO iatrogênica. Entretanto, o alelo Asn680 do polimorfismo Ser680Asn se associou às formas mais graves da SHO iatrogênica / Ovarian hyperstimulation syndrome (OHSS) can occur spontaneously during early pregnancy or as an iatrogenic complication in assisted reproductive medicine. The aim of this study was to identify clinical and hormonal risk factors for iatrogenic OHHS and to evaluate the role of allelic variants of the FSHR in the etiology of this syndrome. We studied 29 patients with moderate and severe iatrogenic OHHS. Age < 33.5 y, basal FSH < 5.2 U/L and estradiol response during ovarian stimulation > 1757 pg/mL were independent risk factors for iatrogenic OHSS and these three factors in association were able to predict the syndrome with accuracy of 78%. We did not find mutations in any patient studied. However, there was a predominance of the Asn680 allele of Ser680Asn polymorphism in patients with the most severe forms of the syndrome