RESUMO
Arteriovenous malformation (AVM) is an anomaly of blood vessel formation. Numerous models have been established to understand the nature of AVM. These models have limitations in terms of the diameter of the vessels used and the impact on the circulatory system. Our goal was to establish an AVM model that does not cause prompt and significant hemodynamic and cardiac alterations but is feasible for follow-up of the AVM's progression. Sixteen female rats were randomly divided into sham-operated and AVM groups. In the AVM group, the saphenous vein and artery were interconnected using microsurgical techniques. The animals were followed up for 12 weeks. Anastomosis patency and the structural and hemodynamic changes of the heart were monitored. The hearts and vessels were histologically analyzed. During the follow-up period, shunts remained unobstructed. Systolic, diastolic, mean arterial pressure, and heart rate values slightly and non-significantly decreased in the AVM group. Echocardiogram results indicated minor systolic function impact, with slight and insignificant changes in aortic pressure and blood velocity, and minimal left ventricular wall enlargement. The small-caliber saphenous AVM model does not cause acute hemodynamic changes. Moderate but progressive alterations and venous dilatation confirmed AVM-like features. The model seems to be suitable for studying further the progression, enlargement, or destabilization of AVM.
RESUMO
Endometriosis is a chronic gynecological disease that causes numerous severe symptoms in affected women. Revealing alterations of the molecular processes in ectopic endometrial tissue is the current policy for understanding the pathomechanisms and discovering potential novel therapeutic targets. Examining molecular processes of eutopic endometrium is likely to be a convenient method to compare it with the molecular alterations observed in ectopic tissues. The aim of the present study was to determine what proportion of the surgically resected eutopic endometrial samples is suitable for further experiments so that these can be comparable with endometriosis. Final hospital reports and histopathology reports of a 3-year-long period (1162 cases) were analysed. The application of a retrospective screening method promoted the categorization of these cases, and quantification of the categorized cases was accomplished. In addition, results obtained from cultured endometrium samples were also detailed. Only a small number of the harvested endometrial samples was suitable for further molecular analysis, while preoperative screening protocol could enlarge this fraction. Applying clinical and histopathological selection and exclusion criteria for tissue screening and histopathological examination of samples could ensure the comparability of healthy endometrium with endometriosis. The present study could be useful for researchers who intend to perform molecular experiments to compare endometriosis with the physiological processes of the endometrium.
RESUMO
DNA replication is fundamental for cell proliferation in all organisms. Nonetheless, components of the replisome have been implicated in human disease, and here we report PRIM1 encoding the catalytic subunit of DNA primase as a novel disease gene. Using a variant classification agnostic approach, biallelic mutations in PRIM1 were identified in five individuals. PRIM1 protein levels were markedly reduced in patient cells, accompanied by replication fork asymmetry, increased interorigin distances, replication stress, and prolonged S-phase duration. Consequently, cell proliferation was markedly impaired, explaining the patients' extreme growth failure. Notably, phenotypic features distinct from those previously reported with DNA polymerase genes were evident, highlighting differing developmental requirements for this core replisome component that warrant future investigation.
