F2-isoprostanes stimulate collagen synthesis in activated hepatic stellate cells: a link with liver fibrosis?

Carbon tetrachloride (CCl4)-induced hepatic fibrosis has been considered to be linked to oxidative stress and mediated by aldehydic lipid peroxidation products. In the present study, we investigated whether collagen synthesis is induced by F2-isoprostanes, the most proximal products of lipid peroxidation and known mediators of important biological effects. By contrast with aldehydes, F2-isoprostanes act through receptors able to elicit definite signal transduction pathways. In a rat model of CCl4-induced hepatic fibrosis, plasma F2-isoprostanes were markedly elevated for the entire experimental period; hepatic collagen content also increased. When hepatic stellate cells (HSCs) from normal liver were cultured with F2-isoprostanes in the concentration range found in the in vivo studies (10(-9)-10(-8) M), a striking increase in DNA synthesis (reversed by the thromboxane A2 antagonist SQ 29 548), in cell proliferation and in collagen synthesis was observed. Total collagen content was similarly increased. Moreover, F2-isoprostanes markedly increased the production of transforming growth factor-beta1 by U937 cells, considered a model of liver macrophages. The data provide evidence for the possibility that F2-isoprostanes generated by lipid peroxidation in hepatocytes mediate HSC proliferation and collagen production seen in hepatic fibrosis.     

Early detachment of titanium particles from various different surfaces of endosseous dental implants

Titanium (Ti) endosseous dental screws with different surfaces (smooth titanium--STi, titanium plasma-sprayed-TPS, alumina oxide sandblasted and acid-etched--Al-SLA, zirconium oxide sandblasted and acid etched--Zr-SLA) were implanted in femura and tibiae of sheep to investigate the biological evolution of the peri-implant tissues and detachment of Ti debris from the implant surfaces in early healing. Implants were not loaded. Sections of the screws and the peri-implant tissues obtained by sawing and grinding were analysed by light microscopy immediately after implantation (time 0) and after 14 days. All samples showed new bone trabeculae and vascularised medullary spaces in those areas where gaps between the implants and host bone were visible. In contrast, no osteogenesis was induced in the areas where the implants were initially positioned in close contact with the host bone. Chips of the pre-existing bone inducing new peri-implant neo-osteogenesis were surrounded by new bone trabeculae. The threads of some screws appeared to be deformed where the host bone showed fractures. Ti granules of 3-60 microm were detectable only in the peri-implant tissues of TPS implants both immediately after surgery and after 14 days, thus suggesting that this phenomenon may be related to the friction of the TPS coating during surgical insertion.     

Recovery of response to adriamycin and cyclophosphamide by lonidamine in previously treated metastatic breast-cancer patients

Thirty-one patients with metastatic breast cancer not responding or progressing after initial response to adriamycin + cyclophosphamide (AC) treatment entered a phase 11 study with oral lonidamine in association to AC. Objective clinical responses were observed in 10 patients (32%) and consisted of 1 complete + 9 partial remissions. Disease stability and progression were observed in 8 and 13 cases, respectively. These results were obtained with a marginal toxicity in addition to that already reported for AC therapy, the main additional side effect being myalgia, which was easily manageable in most cases.     

Primary lymphoma of the liver - a case-report and a review of the literature

A case of primary lymphoma of the liver in a 72-year-old man is reported. The patient showed a three to four month history of abdominal ache, low grade fever, and weight loss. The presence of a large mass occupying the V and VT hepatic segments was demonstrated; no other organs were involved and no evidence of lymphoadenopathy was found. Laboratory tests showed a remarkable increase in ESR, LDH and alkaline phosphatase while CEA and alpha-1 fetoprotein were within the normal values. Two ultrasound-guided needle biopsies on the hepatic lesion did not produce any significant tissue for diagnosis. Therefore the V and VI hepatic segments were excised; a hard, greyish mass with the largest diameter of 6.5 cm, was found at laparatomy. Histology of the surgical specimen showed the presence of a malignant non-Hodgking's B-cell lymphoma, centroblastic-centrocytic, diffuse type (working formulation: G) of intermediate grade of malignancy. Staging was completed with lymphography, and bone marrow biopsy; both proved normal. After the operation adjuvant chemotherapy was commenced (COP for six cycles). Follow-up has so far shown no signs of recurrence after 24 months. In conclusion, the diagnosis of primary lymphoma of the liver is very difficult and is often reached only after histologic evaluation of the surgical specimen. Moreover, this disease has a much more favourable prognosis than the hepatocellular carcinoma and other primary or secondary liver cancers; therefore accurate investigations are important to reach the correct diagnosis.     

The use of recombinant activated factor VII in obstetric and gynaecological haemorrhage

Recombinant activated factor VII (rFVIIa) was originally developed for the treatment of bleeding in patients with haemophilia A or B and inhibitors. Over the past ten years, it has been successfully used to prevent or control bleeding in several other nonhaemophilic bleeding conditions. Among the newer 'off-label' clinical applications of rFVIIa, there is increasing evidence of its effectiveness in treating obstetric and gynaecological bleeding unresponsive to conventional therapy. The existing literature on the use of rFVIIa in obstetrics and gynaecology is summarised in this review. Although supported by few and uncontrolled studies, on the whole, the published data suggest a potential role of rFVIIa in the management of obstetric and gynaecological intractable bleeding. However, further evidence is needed to improve the assessment of its optimal dose, effectiveness and safety in such conditions.