Czy łagodny stan przedrzucawkowy powoduje sztywność tętnic i przebudowę komory serca poprzez zapalenie?

Background: A link between preeclampsia (PE) and excessive maternal morbidity and mortality is a commonly recognized fact. Moreover, it has been suggested that chronic inflammatory state connected with PE contributes to accelerated atherosclerosis. There is also an association between PE and maternal cardiac remodeling and biventricular diastolic dysfunction. The aim of the study was to investigate the presence of impaired myocardial performance and increased arterial stiffness in patients who experienced a mild case of PE five years previously. Methods: The study included forty PE patients (40 women; mean age 33.75±7.95) and 27 healthy volunteers (27 women; mean age 36.44±10.45)Transthoracic echocardiography, including Doppler echocardiography combined with tissue Doppler imaging (TDI), and aortic stiffness index (AoSI), aortic distensibility (AoD), and aortic elastic modulus (AoEM) values were measured in each study participant. Results: There was a statistically significant increase in hsCRP, aortic stiffness index, and aortic elastic modulus in PE patients as compared to controls (2.43±1.91 vs. 3.80±2.06, p=0.007; 3.09±2.41 vs. 7.32±6.89, p=0.001; 2.89±2.11 vs. 7.00± 6.83, p=0.001), while a significant decrease was observed in the aortic strain and distensibility (respectively, 22.35±15.99 vs. 12.24±9.22, p=0.005; 11.17±9.68 vs. 6.13±4.99, p=0.018). No differences between the two groups were observed with regard to the left ventricular myocardial performance index (MPI) (0.55±0.16 vs. 0.53± 0.19, p= 0.630). Conclusions: To the best of our knowledge, this has been the first study to demonstrate impaired aortic elasticity and unaffected myocardial performance index in patients with mild PE. Moreover, these effects turned out to be significantly correlated with inflammation.Wstęp: Istnieje powiązanie pomiędzy stanem przedrzucawkowym (PE) a nadmierną zachorowalnością i śmiertelnością. Ponadto, sugeruje się, że przewlekły stan zapalny udzielający się w PE przyczynia się do przyspieszenia miażdżycy. Istnieje również związek między PE przebudowy mięśnia sercowego ze strony matki i dwukomorową dysfunkcją rozkurczową. Zaplanowaliśmy ocenić w tym badaniu, czy nie została osłabiona wydolność mięśnia sercowego oraz zwiększenie sztywności tętnic u pacjentek, które pięć lat wcześniej miały łagodny przypadek PE. Metody: W badanie włączonych zostało czterdzieści pacjentek (40 kobiet; średnia wieku 33,75±7,95) oraz 27 zdrowych ochotniczek (27 kobiet: średnia wieku: 36,44±10,45). Każda z pacjentek została zbadana za pomocą echokardiografii przezklatkowej, w tym echokardiografii dopplerowskiej w połączeniu z tkankową echokardiografią dopplerowską (TDI). Zostały również zmierzone takie wartości, jak wskaźnik sztywności aorty (AoSI), rozciągliwość aorty, a także moduł sprężystości aorty (AoEM). Wyniki: Stwierdzono statystycznie istotny wzrost hsCRP, wskaźnika sztywności aorty i modułu sprężystości aorty u pacjentów z PE w porównaniu z grupą kontrolną (2,43±1,91vs. 3,80±2,06, p=0.007; 3,09±2,41 vs. 7,32±6,89, p=0,001; 2,89±2,11 vs. 7,00± 6,83, p=0,001), natomiast znaczne zmniejszenie zaobserwowano w odkształceniu aorty i jej rozciągliwości (odpowiednio 22,35±15,99 vs. 12,24±9,22, p= 0,005; 11,17±9,68 vs. 6,13±4,99, p=0.018). Nie wystąpiły różnice pomiędzy tymi dwoma grupami w odniesieniu do wskaźnika wydolności mięśnia sercowego lewej komory (0,55± 0,16 vs 0,53± 0,19, p=0,630). Wnioski: Stwierdziliśmy po raz pierwszy w tym badaniu, że wystąpiły osłabiona elastyczność aorty i niezmieniony wskaźnik wydolność mięśnia sercowego (MPI) u pacjentek z łagodnym PE, ponadto, efekty te były znacząco skorelowane ze stanem zapalnym

Fenotypowe podgrupy zespołu policystycznych jajników mają różne objawy wewnątrznerkowej oporności

Objective: The polycystic ovary syndrome (PCOS) is known to be related with increased metabolic and cardiovascular risks. Various phenotypic subgroups of PCOS have been proven to have metabolic and endocrine disorders with varying degrees of severity. However, intra-renal vascular resistance, which is an indirect indication ofatherosclerosis, remains unknown in PCOS subgroups. In this study we examined whether PCOS subgroups have different intra-renal resistance symptoms. Material and Methods: 98 PCOS patients (diagnosed according to the Rotterdam criteria) 30 controls were ncluded in the study. The diagnosis of PCOS was established in the presence of at least two of the following criteria: 1- oligo and/or amenorrhea (OM); 2- clinic and/or biochemical signs of hyperandrogenism (HA); 3- polycystic ovarian morphology (PCO) detected by transvaginal ultrasonography. 37 patients (Group 1) met all three criteria (HA+OM+PCO), 29 patients (Group 2) met two of the criteria including hyperandrogenism (HA+OM or HA+PCO) and the remaining 32 patients (Group 3) had no hyperandrogenism but fulfilled the other two criteria; PCO+OM. Renal Doppler ultrasonography and hormonal/ biochemical analyses were carried out. The first outcome measure was designated as the differences in the renal resistive index (RRI) values of the groups, and the second outcome measure was designated as the relation of RRI with the insulin resistance and lipid profile. Results: In Group 1, the RRI and the homeostasis model assessment of insulin resistance (HOMA-IR) values were significantly higher than in Group 3 and controls (P < 0.031, P < 0.001, respectively, after adjusting for age and BMI). The RRI and HOMA-IR values in Group 3 were similar to those of the control group. It was determined that RRI has a positive correlation with HOMA-IR (r=0.784, PCel pracy: Zespół policystycznych jajników jest związany ze zwiększonym ryzykiem metabolicznym i sercowonaczyniowym. Fenotypowe podgrupy w obrębie zespołu PCO charakteryzują się zaburzeniami metabolicznymi i endokrynnymi o rożnym stopniu nasilenia. Jednak wewnątrznerkowa oporność naczyniowa, która jest pośrednim wykładnikiem miażdżycy, pozostaje nieznana w podgrupach zespołu PCO. W badaniu ocenialiśmy czy podgrupy zespołu PCO mają rożne objawy wewnątrznerkowej oporności. Materiał i metoda: do badania włączono 98 pacjentek z zespołem PCO (zdiagnozowanym według kryterium z Rotterdamu) oraz 30 pacjentek kontrolnych. Rozpoznanie zespołu PCO postawiono na podstawie obecności przynajmniej dwóch z poniżej wymienionych kryteriów: 1-oligo i/lub amenorrhea (OM); 2-kliniczne lub biochemiczne objawy hiperandrogenizmu (HA); 3-policystyczny obraz jajnikow (PCO) w przez pochwowym badaniu ultrasonograficznym. Grupę 1 stanowiło 37 pacjentek, które spełniły wszystkie kryteria diagnostyczne (HA+OM+PCO), grupa 2 to 29 pacjentek z dwoma kryteriami, w tym kryterium hiperandrogenizmu (HA+OM lub HA+PCO), pozostałe 32 pacjentki to grupa 3 – bez hiperandrogenizmu ale z dwoma pozostałymi kryteriami; PCO+OM. Przeprowadzono badanie dopplerowskie nerek i hormonalno-biochemiczną ocenę. Jako pierwszą zmierzono różnicę pomiędzy grupami w indeksie oporu nerkowego (RRI), następnie oceniono związek pomiędzy RRI a insulinoopornością i profilem lipidowym. Wyniki: W grupie 1, RRI i wskaźnik oceny insulinooporności (HOMA-IR) były istotnie wyższe niż w grupie 3 oraz kontrolnej (

Measurement of choroid thickness in pregnant women using enhanced depth imaging optical coherence tomography

Objetivo: Investigar a espessura da coroide em gestantes saudáveis durante os diferentes trimestres utilizando tomografia de coerência óptica com profundidade de imagem aprimorada (EDI-OCT). Métodos: Este estudo prospectivo incluiu 90 gestantes saudáveis nos primeiro, segundo e terceiro trimestres da gravidez (grupos 1, 2 e 3, respectivamente) e 30 mulheres saudáveis não-gestantes (grupo 4) com faixa etária de 18-40 anos de idade. Foi realizada tomografia de coerência óptica espectral para estimar a espessura média da coroide. A espessura da coroide foi medida manualmente da borda externa do epitélio pigmentar da retina até o limite interno da esclera nas regiões subfoveal, 3 mm temporal e 3 mm nasal à fóvea utilizando EDI-OCT. As diferenças entre os grupos foram analisadas com o teste ANOVA unicaudal. Resultados: Houve diferença estatística significativa na espessura média da coroide entre os grupos 2 e 4 nas regiões subfoveal, temporal e nasal à fóvea (p=0,007; p<0,001; p=0,026, respectivamente). A espessura média da coroide no grupo 2 foi: 395 ± 80 µm, 338 ± 77 µm e 233 ± 61 µm nas regiões subfoveal, temporal e nasal à fóvea, respectivamente. Em comparação, a espessura média da coroide no grupo 4 foi de: 335 ± 86 µm, 275 ± 54 µm e 200 ± 53 µm, nas regiões subfoveal, temporal e nasal à fóvea, respectivamente. Não foi encontrada diferença estatística significativa entre os grupos 1-4 (p=0,214, p=0,177, p=0,094, respectivamente) e os grupos 3-4 (p=0,105, p=0,261, p=0,695 respectivamente), para todas as medidas. Conclusão: Nossos resultados sugerem que há espessamento da coroide nas regiões subfoveal, temporal e nasal à fóvea no segundo trimestre gestacional

Evaluation of peripapillary choroidal and retinal nerve fiber layer thickness in eyes with tilted optic disc

Purpose: This study was performed to evaluate the retinal nerve fiber layer (RNFL) and peripapillary choroidal thickness in eyes with tilted optic disc in order to identify characteristic RNFL and peripapillary choroid patterns verified by optical coherence tomography (OCT). Methods: Twenty-nine eyes of 29 patients with tilted optic discs were studied with spectral-domain (SD)-OCT and compared with age and sex-matched control subjects in a prospective design. The imaging of RNFL was performed using circular scans of a diameter of 3.4 mm around the optic disc using OCT. For measurements of peripapillary choroidal thickness, the standar d protocol for RNFL assessment was performed. Results: SD-OCT indicated significantly lower superotemporal (p<0.001), superonasal (p=0.001), and global (p=0.005) RNFL thicknesses in the tilted disc group than those of the control group. Peripapillary choroid was significantly thicker at the site of the elevated rim of eyes with tilted disc (p<0.001). Conclusion: This study demonstrated a clinical characterization of the main tilted disc morphologies that may be helpful in differentiating a tilted disc from other altered disc morphologies. Further studies are recommended to study the comparison between glaucoma and tilted disc groups

Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling

Organoid technologies have become a powerful emerging tool to model liver diseases, for drug screening, and for personalized treatments. These applications are, however, limited in their capacity to generate functional hepatocytes in a reproducible and efficient manner. Here, we generated and characterized the hepatic organoid (eHEPO) culture system using human induced pluripotent stem cell (iPSC)-derived EpCAM-positive endodermal cells as an intermediate. eHEPOs can be produced within 2 weeks and expanded long term (>16 months) without any loss of differentiation capacity to mature hepatocytes. Starting from patient-specific iPSCs, we modeled citrullinemia type 1, a urea cycle disorder caused by mutations in the argininosuccinate synthetase (ASS1) enzyme. The disease-related ammonia accumulation phenotype in eHEPOs could be reversed by the overexpression of the wild-type ASS1 gene, which also indicated that this model is amenable to genetic manipulation. Thus, eHEPOs are excellent unlimited cell sources to generate functional hepatic organoids in a fast and efficient manner

Pharmacokinetic aspects of retinal drug delivery

Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review article provides a critical discussion of retinal drug delivery, particularly from the pharmacokinetic point of view. This article does not include an extensive review of drug delivery technologies, because they have already been reviewed several times recently. Instead, we aim to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment. This review is based on the literature and unpublished data from the authors' laboratory.Peer reviewe