组成型αB晶体蛋白在热休克蛋白核转录因子1敲除小鼠心肌中的表达

目的:了解热休克蛋白核转录因子1(HSF1)对小鼠心肌组成型αB晶体蛋白(αB-Crystallin,αBC)表达的影响.方法:用western blot和免疫组织化学的方法,测定组成型αBC在HSF1基因野生型(hsf1+/+)和HSF1基因敲除型(hsf1-/-)小鼠心肌中的表达.结果:αBC在hsf1-/-和hsf1+/+小鼠心肌表达量分别为68.42±4.16和100.00±7.58(心肌可溶性组分,P＜0.05),20.35±1.01和37.55±1.91(心肌不可溶性组分,P＜0.05);免疫组化显示αBC在hsf1-/-心肌细胞内的表达信号较hsf1+/+明显减弱.结论:HSF1基因是介导组成型αBC基因表达重要的、但不是惟一的因子.     

Effects of somatostatin on ethanol-induced gastric erosions in the rat: role of mast cells

Somatostatin (S) inhibits hemorrhagic gastric erosions produced by ethanol. In this study we compared the dose-dependent effects of linear (reduced) and cyclic (oxidized) S with respect to mast cell degranulation. The gastric mucosal injuries were more inhibited by linear S than by cyclic S. But linear S aggravated injury at a certain dose (10(-7) mol/rat). Mucosal mast cell degranulation correlated significantly with the area of hemorrhagic mucosal lesions (r = 0.91). Both cytoprotection as well as aggravation potency of S may be connected to gastric mucosal mast cell activity in the rat.     

Effect of bacterial wax esters in sensitized (A) and non-sensitized (NA) human blood cell incubates

Inflammation Research -     

Toxicokinetics of the phytoestrogen daidzein in female DA/Han rats

Female DA/Han rats were given the phytoestrogen daidzein, either intravenously (10 mg/kg b.w.) or orally by gavage (10 or 100 mg/kg b.w.). The plasma concentration-time curve determined after i.v. administration of daidzein was fitted to a triexponential model, resulting in a final half-life (gamma-phase) of approximately 4 h. The oral bioavailability of 10 mg daidzein/kg was 9.7%, while that of 100 mg/kg was 2.2%; the higher dose (100 mg/kg) was apparently absorbed to a four- to fivefold lower extent than the smaller dose. The plasma concentration time curves after oral administration of daidzein to female DA/Han rats revealed pronounced interindividual differences and multiple peaks, pointing to extensive enterohepatic circulation and/or protracted absorption from the gastrointestinal tract. As shown in a separate experiment with bile duct-cannulated rats, daidzein (i.p. 10 mg/kg b.w.) is efficiently excreted with bile: glucuronide/sulfate metabolites amounting to approximately 30% of the dose in 8 h. Conjugates were also the main circulating metabolites upon i.v. or gavage administration of daidzein, indicating efficient phase II metabolism in female DA/Han rats. Since only few data have been published on tissue levels of isoflavones, their concentrations were measured in various organs and compared to plasma levels determined at the time the animals were killed, with one exception 32 or 48 h after rats had received a single dose of daidzein (i.v. or per os). As expected, the daidzein concentrations depended upon dose and administration route. Despite notable differences in the absolute amounts of total daidzein (free plus hydrolyzed conjugates), the levels were usually three- to fivefold higher in liver and kidney than in plasma; in most samples of uteri, the concentrations were similar, or up to twofold higher, than the respective plasma levels. These data point to an uptake and storage of isoflavones and metabolites in tissues. Experimental toxicokinetics appear to be a relevant subject that should be integrated into assessments of toxicological data for endocrine modulators.     

Chronic childhood idiopathic thrombocytopenia purpura: long-term follow-up

An understanding of the natural history of childhood chronic idiopathic thrombocytopenia purpura (ITP) could contribute to a rational therapeutic approach to its treatment, which remains controversial. In our retrospective study of 92 children with ITP, 22 had a chronic course and were followed for 3–14 years (median 8.6 years). Treatment, when indicated, was individualized: 4 patients (18.2%) did not receive any treatment, 14 (63.6%) received steroids only, while 4 (18.2%) were treated with steroids and one of the following: high-dose gamma globulin (4 patients), splenectomy (2 patients) or immunosuppressive therapy (2 patients). During follow-up, 14 patients (63.6%) achieved complete remission, 5 (22.7%) partial remission and only 3 (13.5%) remained severely thrombocytopenic, with minimal bleeding tendency. Eleven patients (50%) responded to the initial prednisone course (1–5mg/kg/day), but showed a marked decrease in platelet count when steroids were tapered off. In view of the high rates of complete and partial remission and the mild course of the few non-responding patients, it is suggested that with adequate supportive therapy, follow-up problems and fatalities can be kept to a minimum. We believe that aggressive therapy, such as splenectomy, should be reserved for the rare symptomatic and severely thrombocytopenic patient.     

Metaanalyse zur prognostischen bedeutung des tumorzellnachweises im knochenmark oder: “Auf der suche nach dem unabhÄngigen prognosefaktor”

Hintergrund

In einer Metaanalyse wurde der Frage nachgegangen, ob in den bisherigen klinischen Studien zum Tumorzellnachweis im Knochenmark die prognostische Bedeutung des Tests bei verschiedenen Tumorentitäten unabhÄngig ist. UnabhÄngigkeit im statistischen Sinne hei\t, da\ durch den Tumorzellnachweis noch weitere relevante prognostische Informationen, zusätzlich zu denen anderer etablierter Faktoren, gewonnen werden können. In den letzten Jahren (1980 bis 1997) sind zum Tumorzellnachweis im Knochenmark zahlreiche Studien erschienen, die in ihrer prognostischen Aussagekraft erheblich differieren. Da der Tumorzellnachweis 1997 optional in die TNM-Klassifikation als M1(i) aufgenommen wurde, wollten Funke et al. [4] durch eine Metaanalyse der wichtigsten Arbeiten zum Thema die Berechtigung einer solchen Empfehlung überprüfen. Insbesondere sollte der Frage nachgegangen werden, ob der Tumorzellnachweis tatsÄchlich ein sinnvoller und unabhÄngiger Prognosefaktor ist.

Methoden

Grundlage der Auswertung waren 112 Arbeiten, die die Autoren aus Medline und Current Contents entnahmen und die dort unter den Stichwörtern “micrometastasis, bone marrow” u. Ä. abrufbar waren. Nach VernachlÄssigung von sehr kleinen Studien (n < 20), mehrfach untersuchten Kollektiven bzw. unklaren prognostischen Aussagen blieben 20 prospektive Arbeiten mit 2 494 Patientinnen übrig. Diese Studien waren bei Patienten mit Mammakarzinomen (11), gastrointestinalen Tumoren (6), Lungentumoren (2) und Kopf-Hals-Tumoren (1) durchgeführt worden. Die statistischen Methoden entsprachen dem Routinehandwerkszeug klinischer Onkologen.

Ergebnisse

UnabhÄngig vom Tumortyp war die Detektionsrate in einem Bereich um 35% (median). In 13 von 20 Studien fand sich eine Korrelation zu anerkannt ungünstigen Prognosefaktoren. 14 Studien zeigten in der univariaten Analyse eine Korrelation von positivem Tumorzellnachweis und reduziertem krankheitsfreien überleben. Aber nur in fünf Studien konnte der Prognosefaktor “Tumorzellen im Knochenmark” als unabhÄngiger Faktor errechnet werden. Für das Gesamtüberleben waren es univariat fünf von zwölf Studien und multivariat zwei von sechs Studien. Das relative Risiko wurde für die Studien beim Mammakarzinom mit 1.34 (1.27 bis 1.42) berechnet.

Schlu\folgerungen

Die Autoren folgern aus ihren Ergebnissen, da\ der Beweis der unabhÄngigen prognostischen Wertigkeit des positiven Tumorzellnachweises bisher noch nicht erbracht werden konnte. Sie fordern vor der Aufnahme ins TNM-System grö\ere prospektive Studien mit standardisiertem Vorgehen.     

Bisphosphonates in the adjuvant treatment of cancer: experimental evidence and first clinical results. International Bone and Cancer Study Group (IBCG)

Several animal models, as well as a number of cell culture experiments, indicate a prophylactic effect of bisphosphonates in respect of subsequent bone metastasis. Moreover, in preliminary clinical trials involving patients with advanced breast cancer and local or remote metastases, biophosphonates produced a reduction in new skeletal metastases. This overview summarizes and discusses the results of the latest investigations. It opens with a section on the pathophysiology of bone metastasis, which is followed by a report on animal models and first studies of bisphosphonate treatment as a new approach in systemic adjuvant therapy.     

Intravenous ibandronate does not affect time to renal function deterioration in patients with skeletal metastases from breast cancer: phase III trial results

As patients with metastatic bone disease typically receive long-term treatment with bisphosphonates, and often antineoplastic compounds, drug-related safety is of considerable importance. Clinical trial data for intravenous (i.v.) ibandronate suggest that its nephrotoxic potential is comparable with placebo. We conducted a post hoc Kaplan-Meier analysis of time to serum creatinine increase with i.v. ibandronate throughout 2 years of treatment. After 96 weeks, 12% of patients in the placebo group and 6% in the ibandronate 6 mg group (ns, P = 0.22) had defined serum creatinine increases. After 12 treatment months (48 weeks), 4% of patients receiving placebo and 2% of patients receiving ibandronate 6 mg showed increased serum creatinine. These results suggest that there is no clinically relevant change in serum creatinine levels with i.v. ibandronate 6 mg infused every 3-4 weeks for 2 years. Comparative trials to examine the renal safety of ibandronate and other i.v. bisphosphonates are warranted.