硫酸长春新碱在0.9%氯化钠注射液中的稳定性研究

本文用紫外分光光度法对硫酸长春新碱在０．９％氯化钠注射液中的稳定性，按经典恒温加速试验法进行了动力学实验研究，结果表明，硫酸长春新碱的降解为一级反应。２５℃，３２℃时硫酸长春新碱的有效期ｔ０．９分别为１２．５１ｈ，８．８６ｈ。为临床合理用药提供了确切的数据。     

Hyaluronidase as an antidote to extravasation ofVinca alkaloids: Clinical results

Skin necrosis is a recognized potential consequence of an inadvertent extravasation ofVinca alkaloids in the surrounding tissues during i.v. administration. Experimental studies suggest that hyaluronidase, an enzyme that degrades hyaluronic acid and improves the absorption of locally injected drugs, can reduce the risk of progressing to skin necrosis. On this basis, we used this enzyme as a local treatment after extravasations ofVinca alkaloids in seven patients. No patient suffered from subsequent skin necrosis. To the best of our knowledge, this is the first clinical report confirming the positive findings of experimental studies on the effectiveness of this antidote.     

Studies on the intracerebral injection of vincristine free and entrapped within liposomes in the rat

The cerebral tissue response and behaviour of rats injected with vincristine of increasing concentration, free and entrapped within liposomes was studied. In separate experiments, blood, urine and brain levels of vincristine were measured after intracerebral injection of free and liposome-entrapped vincristine. When entrapped within liposomes, vincristine clearance from the brain was significantly reduced and the amount of tissue damage was directly related to the amount of drug given, being slightly greater at the same dose when entrapped. These results indicate a potential application for drugs entrapped within liposomes acting as a depot preparation in the treatment of cerebral gliomas.     

Immunotherapy Maintenance in Acute Non-Lymphocytic Leukaemia

Abstract: Between January 1975 and December 1977, 264 adult patients with acute non-lymphocytic leukaemia entered the Australian National Leukaemia Trial. Of 251 evaluable patients, three induction regimens achieved similar complete response (CR) rates. CROP (cytosine arabinoside, daunorubicin, vincristine, prednisolone) produced CR in 41% of patients, 7 and 3 (cytosine arabinoside, daunorubicin) in 42% and 7 and 3 plus hydroxyurea in 52%. Remission duration and survival were similar when induction regimens were compared. Fortyfive patients reaching maintenance therapy were randomised to either chemo-immunotherapy (BCG plus intradermal leukaemic blast cells) or chemotherapy alone. The duration of CR in these two groups was almost identical, though patients receiving chemotherapy alone had prolonged survival (median 161 weeks) when compared to the chemo-immunotherapy group (84 weeks, p = 0.07). Institutions with less developed supportive facilities reported lower CR rates (p =0.04). Leucocytosis, (> 100 × 10⁹/I) and older age (> 50 years) were associated with shortened survival. The Trial has failed to show any advantage for this form of immunotherapy.     

Platelet size distribution in mice following immunothrombopenia and vincristine administration

Summary In the present study platelet size distribution was investigated after induction of immunothrombocytopenia by rabbit-anti-mouse-platelet-serum (RAMPS) and after vincristine-induced thrombocytopenia.The platelet size distribution after a single dose of RAMPS showed a shift to larger volumes at day 1 and 2, and a decrease to slightly smaller volumes than normal at day 8. These differences, however, were not statistically significant.After vincristine administration, a dose-dependent increase of the platelet size distribution was demonstrated, which lasted from day 1–7.It is suggested that in immune-induced thrombocytopenia the young platelets released from bone marrow megakaryocytes are not exclusively large platelets. On the other hand the early appearance of large platelets after vincristine administration points to a toxic or segregating effect of vincristine on circulating platelets. Therefore, in our experiments, the platelet size is not suitable for the differentiation of young and old platelets.This study was supported by the Deutsche Forschungsgemeinschaft. Qu 33/1     

Leukemias induced by ethylnitrosourea in Wistar rats: incidence and chemotherapy.

After application of 15 mg/kg ethylnitrosourea (ENU) weekly for 15 weeks to 200 male Wistar rats, 76 developed acute leukemias, 15 developed chronic myeloid leukemias and 39 had malignomas in other organs. The weekly application of 75 mg/kg ENU to another group of 200 male Wistar rats for 3 weeks caused 57 acute leukemias, 6 chronic myeloid leukemias and 47 malignomas in other organs. From 112 “autochthonous” acute leukemias which were treated with a combination of vincristine, adriamycin and cytosine arabinoside (ADOA), 67 (60%) achieved a complete remission with a median survival time of 64 days (range 25–173). The survival time of this group was significantly increased compared to untreated controls (α = 0.01). Forty-five rats (40%) with acute leukemia died during the first week after start of therapy, or therapy had to be discontinued. The failure of treatment in this group was attributed to the poor general condition of the animals whose platelet counts and hemoglobin values were low, due to late diagnosis.The “autochthonous” acute leukemias demonstrated some parallels with human acute leukemia. Their use in experimental chemotherapy is discussed.     

Treatment of multiple myeloma: a randomized study of three different regimens

The results of an Italian multicentric trial for treatment of symptomatic Multiple Myeloma (MM) are reported. One hundred and thirty-three previously untreated patients were singled out at random for three different chemotherapy schedules: Melphalan plus Prednisone (M.P.) X 6 monthly cycles; Vincristine plus Melphalan plus Cyclophosphamide plus Prednisone (VMCP) X 6 monthly cycles; Peptichemio, Cyclophosphamide, BCNU. Drugs in this latter schedule were administered sequentially, for a period of six months. Criteria for response, progression and relapse were those of the Southwestern Oncology Group. Fifteen patients in MP chemotherapy (35%) and 20 patients in VCMP chemotherapy (46%) achieved an objective response (decrease of at least 50% in the synthesis index of Monoclonal Component (M.C.], while only 3 out of the other 21 patients assigned to the third schedule responded to treatment. No significant differences were noted in the survival curves in either of the three treatment groups. The 38 responding patients did not receive maintenance therapy; no significant difference was found in remission duration between patients in MP and VCMP arms, with a median duration of 16 months for the whole group. No statistical difference was observed between survival and remission curves of patients with a 'response' (M. spike reduction greater than 75%) and those with 'improvement' (M. spike reduction between 75 and 50%). The authors conclude that the inclusion of Vintristine in a combination chemotherapy does not produce clear survival benefits; a longer induction period (12 cycles) could allow a better differentiation between MP and VMCP regimens.     

Ameliorative potential of ferulic acid in vincristine-induced painful neuropathy in rats: An evidence of behavioral and biochemical examination

The present study was designed to investigate the effect of ferulic acid (FA) in vincristine-induced neuropathic pain in rats. Vincristine (50 µg/kg, i.p. for 10 consecutive days) was administered to induce painful neuropathy in rats. Various pain sensitive tests, viz., pinprick, hot plate, paint-brush, and acetone test were performed on different days (1, 6, 14, and 21) to assess the degree of mechanical hyperalgesia, heat hyperalgesia, mechanical dynamic allodynia, and cold allodynia, respectively. The electrophysiological and histopathological evaluations were also investigated. The tissue thiobarbituric acid reactive species (TBARS), reduced glutathione (GSH), myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10), and total calcium were measured as the markers of inflammation and oxidative stress. FA (50 and 100 mg/kg, i.p.) and gabapentin (10 mg/kg, p.o.) were administered for 11 days. Administration of FA attenuated the vincristine-induced behavioral alteration along with electrophysiological and histopathological changes significantly (P < 0.05). FA also attenuated the vincristine-induced oxidative stress (TBARS, GSH, and total calcium levels) and inflammation (MPO, TNF-alpha, IL-6, and IL-10). It may be concluded that FA has ameliorative potential in mitigation of the painful states associated with vincristine-induced painful neuropathy that may further be attributed to anti-inflammatory actions with subsequent reduction in oxidative stress.     

Antinociceptive and anti-allodynic effects of oral PL37, a complete inhibitor of enkephalin-catabolizing enzymes, in a rat model of peripheral neuropathic pain induced by vincristine

Vincristine is a common anti-cancer therapy administered for the treatment of many types of tumors. Its dose-limiting side effect is the production of peripheral neuropathy, resulting in chronic neuropathic pain in many patients. An animal model of vincristine-induced sensory neuropathy was developed after repeated intraperitoneal injection in male rats and used in the present work to study the effects of PL37, an orally active complete dual inhibitor of enkephalin-catabolizing enzymes, on mechanical hypersensitivity and allodynia and on cold allodynia. We used the Electronic Von Frey filament (mechanical static allodynia), acetone test (cold allodynia), and a new behavioural test we first describe in this study, the “paint-brush test” which evaluates dynamic mechanical allodynia and dynamic mechanical hypersensitivity. We used a smooth paint brush leading to an innocuous stimulus, and a rough-one leading to an intense mechanical stimulus. Mechanical hypersensitivity and allodynia due to vincristine-induced neuropathy, but not cold allodynia, are strongly reduced by oral or i.p. injected PL37, the dose-dependent effects being reversed by naloxone-methiodide supporting the peripheral action of the dual inhibitor. These results show that enkephalins protected from degradation by PL37 could bind to peripheral opioid receptors expressed only on C- and Aδ-mechanonociceptors but not on cold thermonociceptors. The fact that PL37 is also active on small intensity mechanical stimulus could reveal an expression of opioid receptors on low threshold mechanoreceptors in the vincrisitine-evoked pathological conditions. Thus the increase in endogenous enkephalin levels induced by PL37 offers a new way to reduced neuropathic pain without the possible side effects of opiates.