The primary objective of drug therapy in portal hypertension is the prevention of variceal bleeding. The use of nonselective -blockers that reduce portal pressure by lowering splanchnic blood inflow 1 has proved effective in this indication. Treatment with propranolol or nadolol reduces the risk of first hemorrhage 2 as well as that of further bleeding episodes in patients with a history of variceal bleeding. 3 However, the average reduction in portal pressure by 15% achieved with -blockers is moderate, 4 and no relevant decrease is observed in more than 30% of patients despite adequate dosage. 5 To enhance the pressure-lowering effect on portal hypertension, -blockers are combined with isosorbide-5 mononitrate, 6 an agent that reduces portal pressure in cirrhosis because of its vasodilator properties. 7 One study demonstrated a mean reduction in portal pressure of 19% during therapy with the combination of propranolol and isosorbide-5 mononitrate. 6 In patients with sodium retention and ascites, however, serious deterioration of renal function was observed with the combination of -blockers and nitrates. 8 The limited effect on portal pressure, the incidence of adverse effects-15% for nonselective -blockers alone, 9 16% for nadolol plus isosorbide-5 mononitrate 10 -and the timeconsuming dose-finding are a stimulant for the search for new antihypertensive substances.Angiotensin II is considered a potential mediator of intrahepatic portal hypertension, because its plasma level is elevated in cirrhosis 11 and its administration induces a rise in portal pressure. 12 Enhancement of the adrenergic vasoconstrictor influence on the portal systems, 13 direct contractile influence on stellate cells, 14 which serve as regulators of the sinusoidal blood flow, 15,16 and sodium and fluid retention induced by the stimulation of aldosterone secretion 17 may be mechanisms that contribute to the portal hypertensive effect of angiotensin II. Losartan is an angiotensin II receptor antagonist with dilatory effects on arteries and veins. 18 The substance has recently been approved for the treatment of arterial hypertension. As yet, its influence on portal hypertension has not been investigated. The aim of this study was to determine the antihypertensive effects of losartan on portal pressure with particular attention paid to potential side effects. PATIENTS AND METHODSPatients. In patients with cirrhosis and esophageal varices, portal hypertension was evaluated by the determination of hepatic venous pressure gradient (HVPG). Thirty consecutive patients with HVPG Ն 20 mm Hg (severe portal hypertension) were assigned to losartan treatment according to the below-mentioned protocol. In accordance with Armonis et al., 19 our preliminary investigations had shown a variability of Ϯ 1 mm Hg in the measurement of HVPG independent from the height of the values. Therefore, this initial selection of patients with high HVPG values was performed to reduce the influence of variability on the percentage change in HVPG caused by losartan. Later,...
Eighteen weeks' treatment of omalizumab in combination with SIT in patients with SAR and comorbid SAA reduced the symptom load during the treatment period but showed no prolonged effect during treatment with SIT only. A slight increase in lung function (FEV1) in patients formerly treated with the omalizumab/SIT combination therapy should encourage further evaluation of long-term effects of omalizumab.
Isolated jaw periosteum-derived cells (JPCs) comprise a morphologically heterogeneous population. There are no known specific surface markers that are able to distinguish between progenitors and cells of other tissue types. The aim of our study was to identify differentiation markers as predictors of JPC mineralization capacity. JPCs underwent osteogenic differentiation after cultivation in osteogenic medium containing known activators. By FACS analysis, we found the low affinity nerve growth factor receptor (LNGFR–CD271) to be induced during the first five days of osteogenesis and that it was expressed at higher levels in mineralizing JPCs (mJPCs) in comparison to non-mineralizing JPCs (nmJPCs). Similar results were obtained by semi-quantitative immunohistochemical stainings and western blot analyses. Quantitative real-time PCR results showed significantly higher LNGFR and alkaline phosphatase transcript levels in mJPCs compared to nmJPCs. LNGFR is a differentiation marker that distinguishes between mineralizing JPCs and non-mineralizing JPCs during the first phase of osteogenesis and can therefore be considered an early surface marker of osteogenic capacity in vitro.
The goal of our research work is to establish mesenchymal osteoprogenitors derived from human jaw periosteum for tissue engineering applications in oral and maxillofacial surgery. For future autologous and/or allogeneic transplantations, some issues must be addressed. On the one hand, animal-free culture conditions have yet to be established. On the other hand, attempts should be undertaken to shorten the in vitro culturing process efficiently. The aim of the present study is to compare and analyze the phenotype of osteoprogenitors from the jaw periosteum under normal FCS-containing and animal-free culture conditions. Therefore, we analyzed the proliferation rates of MesenCult-XF medium (MC-) in comparison to DMEM-cultured JPCs. Whereas jaw periosteal cells (JPCs) show relatively slow proliferation rates and a fibroblastoid shape under DMEM culture conditions, MC-cultured JPCs diminished their cell size significantly and proliferated rapidly. By live-monitoring measurements of adhesion and proliferation, we made an interesting observation: whereas the proliferation of the MSCA-1+ subpopulation and the unseparated cell fraction were favored by the animal-free culture medium, the proliferation of the MSCA-1- subpopulation seemed to be repressed under these conditions. The alkaline phosphatase expression pattern showed similar results under both culture conditions. Comparison of the mineralization capacity revealed an earlier formation of calcium-phosphate precipitates under MC culture conditions; however, the mineralization capacity of the DMEM-cultured cells seemed to be higher. We conclude that the tested animal-free medium is suitable for the in vitro expansion and even for the specific selection of osteoprogenitor cells derived from the jaw periosteum.
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