4－氨基吡啶诱发组胺释放及某些药物的拮抗作用

４－氨基吡啶（４－ＡＰ）有组胺释放作用。小鼠ｉｐ４－ＡＰ５ｍｇ·ｋｇ－１后，肺中组胺含量明显减低，血中组胺含量显著增高。钙拮抗剂硝苯啶、ＴＭＢ－８及钾通道开放剂米诺地尔均能明显抑制４－ＡＰ诱发的小鼠ＰＭＣ释放组胺。结果提示，ＭＣ可能存在钾通道，４－ＡＰ诱发ＭＣ释放组胺可能与它阻滞钾通道，从而使钙通道开放，增加Ｃａ２＋内流有关。     

刺蒺藜果中一种新桂皮酰胺类成分的分离和鉴定

从刺蒺藜(Tribulus terrestris L)果实中分得两个化合物,经理化常数测定和光谱(UV,IR,¹HNMR,¹³CNMR,¹H-¹³CCOSY和MS)解析。化合物I鉴定为N-对羟基苯乙酮基-3-甲氧基-4-羟基取代桂皮酰胺,为一新化合物,命名为蒺藜酰胺(terrestriamide)。化合物II为8-甲基氢化茚酮-1,首次从该植物中获得。     

柴胡皂甙q及其甙元的结构鉴定

从小叶黑柴胡(Bupleurum smithii Wolffvar;parvifolium ShanetY.Li)的根中得到3个化合物,柴胡皂甙元A和Q及柴胡皂甙q。柴胡皂甙元Q和柴胡皂甙q为新化合物,根据理化性质和波谱分析,确定其结构分别为齐墩果烷-11,13(18)-二烯-3β,16β,23,28,30-五醇和3β,16β,23,28,3O-五羟基齐墩果烷-11,13(18)-二烯-3-O-β-D-吡喃葡萄糖基(1→6)-[α-L-吡喃鼠李糖基(1→4)]-β-D-吡喃葡萄糖甙。     

Treatment of progressive Hodgkin's disease with intensive chemoradiotherapy and autologous bone marrow transplantation

Twenty-six patients with progressive Hodgkin's disease after conventional chemotherapy received intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT); 19 also received additional involved-field radiotherapy. Twenty-one patients [81%, 95% confidence intervals (CI) 61% to 94%] attained complete (n = 18) or partial responses. Ten patients (38%, 95% CI 20% to 59%) are disease- free a median of 4.5 years later (range 3.5 to 7.0 years), including seven patients with continuous complete responses. The likelihood of overall response was not significantly influenced by any clinical or treatment variable examined. However, there was a trend favoring patients with higher Karnofsky scores, and higher scores were associated with attainment of complete responses (P = .06 and P = .02, respectively, Mann-Whitney U test). Both higher Karnofsky scores and shorter durations of disease before transplantation were associated with improved survival in a stepwise Cox multivariate analysis. The chief cause of failure was progression at sites previously involved with Hodgkin's disease. No patient relapsed in the marrow, and two of three patients with a history of marrow involvement with Hodgkin's disease achieved durable complete responses after transplantation. These data suggest that inadequate pretransplant conditioning, and not the reinoculation of occult tumor cells in the autologous marrow, caused most relapses. Fatal treatment-related toxicity occurred in six patients. Three patients died of idiopathic interstitial pneumonitis; each had previously received local mediastinal irradiation before intensive chemoradiotherapy. Intensive chemoradiotherapy and ABMT produces durable responses in some patients with Hodgkin's disease incurable with conventional therapy. Use of such therapies at the first sign of failure with conventional chemotherapy and development of more effective conditioning regimens should further improve results.     

The effect of local anesthetic and corticosteroid combinations on chondrocyte viability

Purpose

Local anesthetic and corticosteroid combination injections are often used in clinical practice, however research investigating the chondrotoxic properties of these combinations is minimal. The goal of this study was to evaluate the effect of single injection doses of 1% lidocaine or 0.25% bupivacaine in combination with single injection doses of dexamethasone sodium phosphate (Decadron^?), methylprednisolone acetate (Depo-Medrol^?), betamethasone sodium phosphate and betamethasone acetate (Celestone^? Soluspan^?), or triamcinolone acetonide (Kenalog^?) on human chondrocyte viability.

Methods

All treatment conditions were delivered to human chondrocytes in vitro for the medication’s respective average duration of action using a bioreactor containing a continuous infusion pump constructed to mimic joint fluid metabolism. A two-color fluorescence assay was used to evaluate cell viability. A mixed-effects regression model was used to evaluate the mean differences in cell viability between treatment groups.

Results

At 14?days, a single injection dose of 1% lidocaine or 0.25% bupivacaine in combination with betamethasone sodium phosphate and betamethasone acetate solution illustrated significant chondrotoxicity when compared with the local anesthetics alone (P?P?=?0.013; P?=?0.016, respectively) when used in combination with 1% lidocaine compared with lidocaine alone, but showed no significant chondrotoxicity in combination with 0.25% bupivacaine (P’s?=?n.s.).

Conclusions

Clinicians should use caution when injecting 1% lidocaine or 0.25% bupivacaine in conjunction with betamethasone sodium phosphate and betamethasone acetate solution due to its pronounced chondrotoxic effect in this study. 1% lidocaine used in combination with methylprednisolone acetate or triamcinolone acetonide also led to significant chondrotoxicity.     

Engraftment of bone marrow cells into normal unprepared hosts: effects of 5-fluorouracil and cell cycle status

Bone marrow from animals treated with 5-fluorouracil (5FU) competes equally with normal marrow when assessed in vivo in an irradiated mouse, but shows markedly defective engraftment when transplanted into noncytoablated hosts. Using Southern Blot analysis and a Y-chromosome specific probe, we determined the level of engraftment of male donor cells in the bone marrow, spleen, and thymus of unprepared female hosts. We have confirmed the defective engraftment of marrow harvested 6 days after 5FU (FU-6) and transplanted into unprepared hosts and shown that this defect is transient; by 35 days after 5FU (FU-35), engraftment has returned to levels seen with normal marrow. FU-6 marrow represents an actively cycling population of stem cells, and we hypothesize that the cycle status of the stem cell may relate to its capacity to engraft in the nonirradiated host. Accordingly, we have evaluated the cycle status of engrafting normal and FU-6 marrow into normal hosts using an in vivo hydroxyurea technique. We have shown that those cells engrafting from normal marrow and over 70% of the cells engrafting from FU-6 marrow were quiescent, demonstrating no killing with hydroxyurea. We have also used fluorescent in situ hybridization (FISH) analysis with a Y-chromosome probe and demonstrated that normal and post-5FU engraftment patterns in peripheral blood were similar to those seen in bone marrow, spleen, and thymus. Altogether these data indicate that cells engrafting in normal, unprepared hosts are dormant, and the defect that occurs after 5FU is concomitant with the induction of these cells to transit the cell cycle.