Background/Aims: Cyclosporine A (CsA) is a commonly used immunosuppressive agent. In some patients treatment with CsA has to be continued during pregnancy. The aim of the study was to assess in an experimental model whether the exposure to CsA during fetal life influences the number and volume of glomeruli, kidney function and blood pressure in the offspring. Methods: Eight pregnant female Sprague-Dawley rats were allocated to 2 treatment regimens: with CsA or solvent. Blood pressure was measured in the offspring at 7 and 11 weeks of age and albuminuria was determined at 11 weeks of age. In the kidney the number and mean volume of glomeruli was assessed using stereological methods. Results: In the offspring of pregnant rats treated with CsA the number of glomeruli was significantly lower and the mean volume of glomeruli was higher when compared to the offspring of pregnant rats receiving solvent. Systolic and diastolic blood pressures as well as albuminuria were significantly higher in the offspring of mothers treated with CsA during gestation compared to the offspring from the control group. Conclusions: Exposure of rats to CsA during fetal life impairs kidney development, thus potentially predisposing to chronic kidney disease and hypertension in the adult life.

The aim of this study was to verify whether L-lactide/DL-lactide copolymer 80/20 (PLDLLA) and platelet-rich plasma (PRP) trigger bone formation within critical-sized calvarial defects in adult sheep (n = 6). Two craniectomies, each ca. 3 cm in diameter, were created in each animal. The first craniectomy was protected with an inner polylactide membrane, filled with PRP-polylactide granules, and covered with outer polylactide membrane. The second control craniectomy was left untreated. The animals were euthanized at 6, 7, 17, 19, 33, and 34 weeks after surgery, and the quality and the rate of reossification were assessed histomorphometrically and microtomographically. The study demonstrated that application of implants made of PLDLLA 80/20 combined with an osteopromotive substance (e.g., PRP) may promote bone healing in large calvarial defect in sheep. These promising proof-of-concept studies need to be verified in the future on a larger cohort of animals and over a longer period of time in order to draw definitive conclusions.

Purpose. Synthetic meshes are now widely used for a repair of various tissue defects. Polypropylene meshes (PPMs), the type most frequently used for repair of abdominal wall defects, have some disadvantages, therefore the development of new mesh materials for reconstructive surgery is an important topic. A TiNibased alloy superelastic mesh implant has been compared with a PPM in the Wistar rat model. Experimental. A midline resection abdominal wall defect (2 cm×3 cm) was treated with a mesh implant (2.5 cm×3.5 cm). Three groups of 20 animals were assessed: (1) a TiNi-based alloy mesh (TNM) group with the defect managed by a TiNi-based wire woven implant; (2) a PPM group with the defect repaired by Optomesh®; and (3) a no-mesh (NM) group treated without the use of any prosthetic material for systemic reaction to implant control. Evaluation of both mesh implantations was carried out on days 14, 28, 56 and 90 after surgery. The following data were compared: general condition of the animals, macroscopic evaluation of the implant area and microscopic evaluation of the tissue surrounding the mesh with the use of scanning electron and light optical microscopy. Results. All the animals from NM group developed hernias. The PPM group showed satisfactory results, although some complications like implant dislocation (6/20) and hernia recurrence (5/20) were noted. In the TNM group neither shrinkage nor implant dislocation were observed. Compared with the PPM group, the TNM group was characterized by no inflammation reaction and better integration with tissues. Conclusions. Suppression of inflammation response together with a more physiological wall remodeling process than with PPM makes TNM an attractive concept for abdominal wall defect reconstruction. Since there was neither shrinkage nor dislocation of the TNM itself it may be suitable for intraperitoneal management. The essence of enhanced biocompatibility is due to stress-strain mechanical behavior of TNM and its surface oxycarbonitride layer, which facilitate its incorporation. Summarizing, TNM was found to be a very promising material for the repair of abdominal wall defects in clinical practice. Ideally TNM would be applied in circumstances when there are indications for the management of large hernias by PPM.

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Background and Aims: Experimental models using carbon tetrachloride (CCl4) and D-galactosamine (D-GalN) can be used in preclinical assessment of acute liver failure (ALF) therapies. Unfortunately, these models are characterized by different dynamics of liver injury depending on the animal strain, administered hepatotoxin, and its dose. The aim of this study was to compare known rat and mouse models of ALF with a view to their future introduction into preclinical cell therapy experiments. In particular, based on histopathological and molecular changes, we suggested experimental time cut-off points for an effective stem cell therapeutic intervention. Methods: ALF was induced by a single intraperitoneal injection of CCl4 in mice (50 µL/100 g b.w.) and rats (200 µL/100 g b.w.) and D-GalN in mice (150 mg/100 g b.w.) and rats (50 mg/100 g b.w.). Blood and liver samples were collected 12 h, 24 h, 48 h and 7 days after intoxication. Blood morphology, liver function blood tests, histopathological changes, proliferation activity, apoptosis, fibrosis, and gene expression were analysed to assess liver damage. Results: At 12 h, 24 h, and 48 h after CCl4 injection, mouse livers showed moderate inflammatory infiltration and massive pericentral necrosis. In rats treated with CCl4, minor lymphocytic infiltration in the liver parenchyma was seen at 12 h, followed by necrosis that appeared around central veins at 24 h and persisted to 48 h. In D-GalN-injected mice, the first histopathological signs of liver injury appeared at 48 h. In the livers of D-GalN-treated rats, moderate pericentral inflammatory infiltration occurred after 12 h, 24 h, and 48 h, accompanied by increased proliferation and apoptosis. All histological changes were accompanied by decreasing expression of certain genes. In most experimental groups of rats and mice, both histological and molecular parameters returned to the baseline values between 48 h and 7 days after intoxication. Conclusions: In mice and rats with CCl4-induced ALF, signs of liver failure can be seen as early as 12 h and develop to 48 h. In the D-GalN-induced model, mice are more resistant to the hepatotoxic effect than rats (after 12 h), and the early hepatitis phase can be observed much later, after 48 h. These cut-off points seem to be optimal for suppressing inflammation and applying effective stem cell therapy for acute liver injury.