In vitro undetectable PT and Fibrinogen (and in vivo?)

A 81 aged woman came to E.R. of Trieste University Hospital with a traumatic head injury. Blood cells count, liver enzymes and other parameters were normal, but with a photometric clot detection method PT and PT-derived Fibrinogen were undetectable, Fibrinogen-Clauss gave different results (157 to 357 mg/dL) and aPTT-Ratio was normal (0.96). When the instrument detection performance was improved, PT was normal and PT-derived Fibrinogen detectable, but Fibrinogen-Clauss was still very unsteady (352/294/558 mg/dL). When a mixing test was performed with normal pool plasma, PT was corrected, PT-derived Fibrinogen was very low (80 mg/dL) and Fibrinogen-Clauss resulted 360 mg/dL. Fibrinogen-Antigen was 368 mg/dL by a nephelometric immunoassay. In another Lab with a different optical analyzer, PT and aPTT yielded the same results, Fibrinogen-Clauss was 557 mg/dL with 35 IU/ml Thrombin reagent (and a very steep clot formation curve), but 113 mg/dL with 15 IU/ml Thrombin reagent (and a normal curve). With an electromechanical clot detection method, PT-INR and aPTT-Ratio were normal (0.88 and 0.96 respectively), Fibrinogen-Clauss was normal (400 mg/dL) but unsteady. However in a few days our patient healed up perfectly; she declared that her sister had the same performance when she was referred to another Hospital for a check-up, nonetheless they never had any severe bleeding in their life. Samples from our patient\u2019s son and daughter were taken and resulted completely normal for coagulation tests. We hypothetized: 1) a too fast Thrombin formation and/or Fibrinogen consumption, as shown by steep coagulation curves without a stable plateau; 2) an excessive thrombin formation, (in preliminary studies, however, G20210A mutation was absent and F1+2 were normal); 3) a dysfibrinogenemia, (to be studied). Further studies for Endogenous Thrombin Potential about thrombin ipothesis and for genetical pattern about fibrinogen molecule are needed to clarify this case

Giant omphaloceles with a small abdominal defect: Prenatal diagnosis and neonatal management

A giant omphalocele is a liver-containing protrusion through an abdominal defect wider than 5 cm in diameter. The giant form with a small abdominal wall defect is a rare condition which, to our knowledge, has not been described previously. We describe three cases with the typical features of elongated vascular liver pedicle and angiomatosis of the hepatic portal system. The abnormal liver organogenesis, due to extra-abdominal development, represented a significant risk factor for hepatic thrombosis after visceral reduction and liver rotation. All the neonates underwent surgery on the first day of postnatal life. One died because of a postoperative liver infarction, and the survivors needed prolonged respiratory support. Prenatal sonographic features, timing, delivery, type of surgical repair, and postnatal outcome are reviewed. A prenatal sonographic diagnosis could be useful to evaluate the abdominal ring and serial ultrasound examinations are recommended to detect promptly ominous signs of hepatic and bowel damage. Color Doppler may be useful to assess the anatomy of the abdominal vessels and their relationships with the herniated organs, although it was not used in any of the cases reported here. This congenital malformation might be considered as a pathological entity separate from giant omphalocele with large abdominal defect, with a severe prognosis due possibly to its different embryological development

Serum Response Factor depletion affects the proliferation of the hepatocellular carcinoma cells HepG2 and JHH6

For hepatocellular carcinoma (HCC), a leading cause of cancer death world-wide, there is no effective therapy especially for the advanced stage of the disease. Thus, we started the investigations about a novel anti HCC approach based on the depletion of the transcription factor serum response factor (SRF) in HCC cell lines; SRF choice was based on its recently proposed contribution to HCC tissue development and on its important role in cell proliferation. SRF depletion, obtained by a siRNA (siSRF797), was studied in two HCC cell lines, i.e. HepG2 and JHH6 assigned to high and lowhepatocytic differentiation grade on the base of the capacity to synthesize albumin. In the HCC cell lines examined, siSRF797 reduced both the mRNA and protein levels of SRF without inducing unspecific interferon response or cytotoxicity. Moreover, SRF depletion induced the reduction of S-phase cells and a decrease in cell number and vitality. Particularly in HepG2, cell growth impairment was paralleled by the decrease of the levels of the transcription factor E2F1 together with some of its regulated genes. In HepG2 but not in JHH6, SRF depletion was associated with apoptosis. Finally, in both HepG2 and JHH6, the combined administration of siSRF797 and bortezomib, a proteasome inhibitor whose therapeutic potential for HCC is considered attractive, further reduced cell viability compared to either siSRF797 or bortezomib treatment alone. In conclusion, SRF depletion affects the expansion of the high and low differentiation grade HCC cells HepG2 and JHH6. These results can pave the way to understand the role of SRF in HCC development and possibly to identify novel anti HCC therapeutic strategies

GIANT OMPHALOCELES WITH A SMALL ABDOMINAL DEFECT: PRENATAL DIAGNOSIS AND NEONATAL MENAGEMENT.

8nonenonePELIZZO G; MASO G; DELL'OSTE C; D'OTTAVIO G; BUSSANI R.; UXA F; CONOSCENTI G; SCHLEEF J.GIANTPelizzo, G; Maso, G; Dell'Oste, C; D'Ottavio, G; Bussani, Rossana; Uxa, F; Conoscenti, G; SCHLEEF J., Gian

Inhibitory effects of fenofibrate on apoptosis and cell proliferation in human endothelial cells in high glucose

Fenofibrate has beneficial effects on the progression and clinical emergence of atherosclerosis in normoglycemic and in diabetic patients. Given the involvement of endothelium in these processes, we speculated that fenofibrate may influence endothelial cell apoptosis and proliferation, regulators of endothelium integrity. Fenofibrate effects on apoptosis and proliferation were studied in human umbilical vein endothelial cells under normal (5.5 mmol/l, NG) and high (22 mmol/l, HG) glucose with or without fenofibrate (50 micromol/l). Apoptosis was evaluated by annexin V, by poly(ADP-ribose) polymerase protein cleavage, and cyclooxygenase-2 (COX-2), Bax/Bcl-2, and p53 protein levels; proliferation was assessed by determining cell cycle phase distribution and the amounts of the cell cycle regulators E2F1, cyclin D1, E1, and A and the levels of the hyper-phosphorylated form of the retinoblastoma protein (ppRb). HG resulted in increased (p<0.05) apoptosis rate associated with COX-2 protein overexpression, without modification of Bax/Bcl2 ratio and p53 levels. Fenofibrate decreased apoptosis and normalized increased COX-2 expression in HG (p<0.05). Both in HG and NG, fenofibrate dramatically reduced cell proliferation (p<0.05) through a G1/G0 block mediated by the reduction in ppRb and the decrease in E2F1, cyclin E1, A, and D1 protein expression, with a mechanism that, for cyclin E1, occurred at the posttranscriptional level. In conclusion, our data show that fenofibrate reduces apoptosis caused by HG but severely interferes with endothelial cell proliferation both in NG and HG. The resulting effect may influence endothelium integrity in vivo and may impact the outcome of acute complications of atherosclerosis in diabete