Učinci prenatalne i postnatalne izloženosti perfluorooktanskoj kiselini na ekspresiju glavnih gena povezanih s reprodukcijom u mišjem hipotalamusu i spolnim žlijezdama

Perfluorooctanoic acid (PFOA), a ubiquitous environmental pollutant reported to be an endocrine disruptor, is used in many industrial and consumer products. Although the adverse effects of PFOA on the reproductive health of animals and humans have been widely reported, most studies have focused on assessing the anatomical features and conventional histology of adult gonads. Therefore, the molecular mechanisms activated in the hypothalamus and gonads following PFOA exposure during the pre- and postnatal periods are not clear. This study used a mouse model to evaluate the effects of PFOA exposure on the alteration of molecular mechanisms in the hypothalamus and gonads during the prenatal and postpartum periods. Changes in gene and protein expression following PFOA exposure were evaluated by quantitative polymerase chain reaction and Western blotting, respectively. Kisspeptin 1 and gonadotropin-releasing hormone expression in the hypothalamus of female and male mouse pups was significantly decreased. Additionally, Cyp17a1 expression was upregulated in male offspring testes, while Cyp17a1 and Cyp19a1 expression was downregulated in female offspring ovaries. Changes at the molecular level due to PFOA exposure in the early stages of development did not show sex-related differences in the hypothalamus; however, such differences were confirmed in the gonads. These results could be used as basic data to study the molecular mechanisms underlying the reproductive dysfunction caused by PFOA exposure in the early stages of embryonic development.Perfluorooktanska kiselina (PFOA) sveprisutna je onečišćujuća tvar za okoliš, za koju je zabilježeno da uzrokuje i endokrinopatije, a upotrebljava se u mnogim industrijskim proizvodima. Bez obzira na poznate i zabilježene nuspojave PFOA-e na reproduktivno zdravlje životinja i ljudi, većina se istraživanja usredotočuje na procjenu anatomskih histoloških značajki u spolnim žlijezdama odraslih jedinki. Molekularni mehanizmi koji se aktiviraju u hipotalamusu i spolnim žlijezdama nakon izlaganja PFOA-i stoga nisu razjašnjeni. U ovom je istraživanju upotrijebljen mišji model za procjenu učinaka izlaganja PFOA-i na promjenu molekularnih mehanizama u hipotalamusu i spolnim žlijezdama za vrijeme prijeporođajnog i poslijeporođajnog razdoblja. Promjene u ekspresiji gena i proteina nakon izloženosti PFOA-i analizirane su kvantitativnom PCR metodom i metodom Western blotting. Ekspresija kispeptina 1 i hormona koji oslobađa gonadotropin u hipotalamusu ženske i muške mladunčadi bila je znakovito smanjena. Osim toga ekpresija Cyp17a1 bila je pojačana u testisima muških potomaka, dok je ekspresija Cyp17a1 i Cyp19a1 u jajnicima ženskih potomaka bila smanjena. Kod promjena na molekularnoj razini u hipotalamusu u ranim razvojnim stadijima nije bilo razlike među spolovima, dok je kod promjena u spolnim žlijezdama povrđena razlika među spolovima. Rezultati ovog istraživanja mogli bi biti korisni kao osnovni podaci u proučavanju molekularnih mehanizama podležeće reproduktivne disfunkcije uzrokovane izloženošću PFOA-i u ranim stadijima embrionalnog razvoja

Epigenetic toxicity and cytotoxicity of perfluorooctanoic acid and its effects on gene expression in embryonic mouse hypothalamus cells

Premda je perfluorooktanska kiselina (PFOA) dobro znana kao endokrini disruptor, i dalje se malo zna o mehanizmima u pozadini njezina djelovanja na stanice i njezine toksičnosti u kritičnoj fazi razvoja hipotalamusa. Stoga smo istražili njezino djelovanje u staničnoj liniji N46 hipotalamusa mišjeg embrija (mHypoE-N46) da bismo saznali o mehanizmima kroz koje ih PFOA oštećuje. S tom smo svrhom analizirali vijabilnost stanica, globalnu metilaciju DNA i gensku ekspresiju izloženih stanica. Porastom koncentracija PFOA padala je stanična vijabilnost, a globalna DNA metilacija rasla. Usto je PFOA značajno utjecala na ekspresiju gena povezanih s apoptozom i staničnim ciklusom, neurotrofnih gena te Tet, Dnmt i Mecp2 gena. Naše istraživanje ukazuje na to da izloženost PFOA utječe na preživljenje stanica hipotalamusa mišjeg embrija reprogramiranjem obrazaca metilacije DNA te promjenama u genima zaduženim za održavanje homeostaze. Metilacija DNA i promjene u ekspresiji Mecp2 gena izazvane djelovanjem PFOA također imaju široki spektar implikacija, budući da utječu na promjene u genima zaduženim za druge važne mehanizme u embrijskom hipotalamusu. Stoga naše istraživanje može poslužiti kao dobra polazna točka za daljnje istraživanje mehanizama djelovanja PFOA na razvoj hipotalamusa.Even though the endocrine-disrupting potential of perfluorooctanoic acid (PFOA) is well known, the mechanisms underlying its cellular and epigenetic toxicity at the critical stage of hypothalamic development are poorly understood. This is why we studied its effects on the embryonic mouse hypothalamic cell line N46 (mHypoE-N46) with a hope to shed more light on the mechanisms through which PFOA causes embryonic hypothalamic cell damage. To do that, we studied cell viability, global DNA methylation, and gene expression in cells exposed to PFOA. As the PFOA dose increased, cell viability decreased, while global DNA methylation increased. PFOA also significantly altered the expression of genes related to the apoptosis and cell cycle, neurotrophic genes, and the Tet, Dnmt, and Mecp2 genes. Our findings suggest that exposure to PFOA affects cell survival through the reprogramming of embryonic hypothalamic DNA methylation patterns and altering cell homeostasis genes. DNA methylation and changes in the Mecp2 gene expression induced by PFOA also imply wider ramifications, as they alter genes of other major mechanisms of the embryonic hypothalamus. Our study may therefore serve as a good starting point for further research into the mechanisms of PFOA effect of hypothalamic development

Photodynamic Therapy for Subretinal New Vessels

Photodynamic therapy (PDT) involves the induction of endothelial cell death or occlusion of blood vessels. On the basis of this mechanism of action, PDT is used in the treatment of predominant classic choroidal neovascularization (CNV), if the classic component is over 50%, and in myopic CNV. This study describes 2 cases of distinctive, abnormal, large, subretinal new vessels that are thought to have originated from the choroids. Diminishment of the new vessels was observed following treatment with PDT

Adenoma of the nonpigmented ciliary epithelium presenting with recurrent iridocyclitis: unique expression of glial fibrillary acidic protein

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Effects of Chromium Methionine Supplementation on Blood Metabolites and Fatty Acid Profile of Beef during Late Fattening Period in Holstein Steers

The objective of this study was to determine the effects of chromium methionine (Cr-Met) chelate supplementation on blood metabolites and fatty acid profile of beef from Holstein steers during late fattening period. Fifteen Holstein steers were allotted randomly into two groups including the control (non Cr-Met feeding, NCM, ave. body weight [BW] = 483±25.7 kg) and the treatment (Cr-Met feeding for 4 months, 4CM, ave. BW = 486±27.5 kg) group. The feeding amount of Cr-Met to animals was limited to 400 ppb/cow/d and was supplemented to total mixed ration. No difference in blood albumin, alkaline phosphatase, urea-nitrogen, calcium, creatine, glucose, total protein, triglyceride, and cholesterol were observed between the treatment groups (p>0.05). The level of high density lipoprotein was higher in the 4CM group than the NCM group, whereas low density lipoprotein was lower in the 4CM group (p0.05). The arachidonic acid level tended to be higher in the 4CM than the NCM group (p = 0.07). Cr-Met had no influence (p>0.05) on the ratio of saturated, unsaturated, unsaturated/saturated, monounsaturated/saturated and polyunsaturated/saturated fatty acids whereas the ratio of polyunsaturated fatty acids (PUFA) in the 4CM group was comparatively higher than the NCM group (p<0.05). This study concluded that feeding Cr-Met supplementation in 400 ppb/d to Holstein steers for 4 months during late fattening period can improve some blood metabolites and beef quality by increasing PUFA and gamma-linoleate compositions of beef

Benign Metastasizing Leiomyoma with Multiple Lymph Node Metastasis: A Case Report

This is a case report about benign metastasizing leiomyoma with multiple lymph node metastasis. A 34-year-old woman received an abdominal myomectomy for a suspicious leiomyoma. On the pathology report, atypical leiomyoma was suspected. Due to the suspicion of multiple lymph node metastasis on pelvis computed tomography (CT) 1 year after the operation, she was transferred to the Samsung Medical Center on October, 2009 for further work up. According to original slide review, it was determined to be a benign leiomyoma with a mitotic count <5/10 high-power fields, little cytological atypia and no tumor cell necrosis. Additional immunostaining was done. Multiple lymph node metastasis and a small lung nodule were identified on positron emission tomogarphy-CT and chest CT. Extensive debulking surgery and diagnostic video-assisted thoracoscopic surgery (VATS) wedge resection were subsequently done. Metastatic lesions were reported to have a histology similar to that of the original mass. VATS right upper lobectomy with mediastinal lymph node dissection was performed because of the pathology result of VATS (adenocarcinoma). She started taking an aromatase inhibitor (Letrozole®) and there was no evidence of recurrence of disease on an imaging study and no post-operative complications until recently

Successful Hemostasis with Recombinant Activated Factor VII in a Patient with Massive Hepatic Subcapsular Hematoma

Recombinant activated coagulation factor VII (rFVIIa) is known to be effective in the management of acquired deficiencies of factor VII and platelet function defects. But recently, rFVIIa has been successfully used to treat ongoing bleeding in disseminated intravascular coagulopathy (DIC) condition. The patient reported here was suspected to be suffering from toxic hepatitis on admission. After percutaneous liver biopsy, bleeding occurred and did not stop even after right hepatic artery embolization. The patient developed a severe hemorrhage that resulted in hypovolemic shock, hemoperitoneum, and a massive subcapsular hematoma. The patient then developed DIC due to massive transfusion, as well as acute liver necrosis. The patient was given 400 μg/kg of rFVIIa. Recombinant factor VIIa was administered in an attempt to control the bleeding. This stabilized the hemoglobin levels of the patient. The patient gradually recovered in 4 months. In conclusion, this case suggests that rFVIIa can be successfully used for the hemostasis of uncontrolled bleeding in DIC