Photodynamic therapy of tumours: value of quantum chemical procedures for characterization of new drugs. Prediction of the electronic structure of zinc(II) phthalocyanine with special emphasis on triplet state excitation energies

Zinc(II) phthalocyanine is the active component of the liposomal formulation CGP 55847 which showed a high activity in photodynamic therapy in a variety of animal tumours. The photophysical properties of zinc(II) phthalocyanine have been studied in detail and compared to those of Photofrin, the only sensitizing agent approved so far for phase III/IV clinical trials. Since the efficacy of photodynamic therapy intrinsically depends on the spectroscopic features of the sensitizer, quantum chemical methods have proven to be an efficient means for optimizing chemical structures. As will be shown, a simple modification of the time-honoured INDO model of Pople allows a prediction of the singlet and triplet state properties of molecules of the size of zinc(II) phthalocyanine with an rms error of ≤ 1000 cm⁻¹.     

Nafenopin, a hypolipidemic and non-genotoxic hepatocarcinogen increases intracellular calcium and transiently decreases intracellular pH in hepatocytes without generation of inositol phosphates

Addition of nafenopin (30-300 microM to 45Ca2+ preloaded cultured hepatocytes caused a rapid and concentration-dependent increase in 45Ca2+ efflux in a manner similar to vasopressin, as evidenced by the loss of radioactivity from the cells. In contrast to vasopressin, addition of nafenopin to [3H]inositol prelabelled hepatocytes in culture did not increase [3H]inositol phosphate production. When added simultaneously with vasopressin, nafenopin inhibited the vasopressin-stimulated [3H]inositol phosphate production. In hepatocyte suspensions isolated from rats treated for 1 week with a carcinogenic dose of nafenopin (1000 ppm in their daily food) the incorporation of [3H]inositol into the phosphoinositide fraction, particularly phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate, was much less than that in hepatocytes isolated from untreated rats. The vasopressin-stimulated [3H]inositol phosphate production was also decreased. Experiments with hepatocyte suspensions preloaded with Ca2+ or pH sensitive fluorescent indicators demonstrated that addition of nafenopin caused an increase in intracellular free Ca2+ and transient acidification of the cells. The increase in [Ca2+]i was decreased by only about 25% when extracellular calcium was removed indicating that nafenopin mainly mobilizes Ca2+ from intracellular stores. The recovery to basal pH was amiloride-sensitive indicating the importance of Na+/H+ exchange in pH recovery after intracellular acidification. Amiloride also inhibited DNA synthesis induced by nafenopin and by epidermal growth factor in cultured hepatocytes; but this effect occurred concomitantly with inhibition of basal DNA synthesis. We suggest that hepatic Ca2+ mobilization induced by nafenopin may play an important role in the mechanism by which nafenopin exerts its physiological as well as its tumour promotive activity upon chronic treatment with carcinogenic doses.     

Retrohepatic vena cava reconstruction with polytetrafluoroethylene graft

The case of an 18-month-old male who underwent a right hepatic lobectomy for hepatoblastoma with extensive involvement of the retrohepatic vena cava is presented. The retrohepatic vena cava was replaced with an expanded polytetrafluoroethylene graft. This graft was proved patent by ultrasonography 2 years after operation. The child has no evidence of recurrent hepatoblastoma. The results of grafting the retrohepatic vena cava have been notoriously poor. It is widely believed that a prosthetic vena cava graft cannot be expected to remain patent. Our experience with polytetrafluoroethylene and previous reports using Dacron and polytetrafluoroethylene have shown that long-term patency of retrohepatic vena cava replacement with synthetic graft can be successful.     

Qualitative radiographic diagnosis of osteo-arthritis of the knee joint in the C57BL mouse

Experiments were performed to assess the diagnostic value of radiography in osteo-arthritis (OA) of the knee joint in C57Bl mice. Comparative histological and radiographic examination of knee joints from 96 animals showed that if the classical diagnostic criteria (narrowing of the joint space, sclerosis of the subchondral bone, deformation of the joint epiphyses) are applied, OA is not readily detectable by radiography. If these criteria are extended to include radiographic changes in the menisci (enlargement, deformation, increased and/or heterogeneous density), the frequency of detection is much improved. However, except in the severest forms of OA, radiography does not afford a satisfactory means of distinguishing between various degrees of severity. The qualitatively evaluated data nevertheless do suggest that quantitative radiographic diagnosis of OA of the murine knee joint may be useful, both for improving the detection rate and for discriminating various degrees of OA.     

Nosology of osteochondrosis dissecans of the trochlea of the talus

The histories of 56 patients with the diagnosis "osteochondrosis dissecans tali" were retrospectively analyzed with regard to etiology, localization, therapy, course, and prognosis. Some of the patients were reexamined. In 33 patients it is highly probable that the osteochondrosis dissecans was not associated with the sequelae of osteochondral fractures. The typical X-ray image is that of a medial, deep osteolysis on the trochlea of the talus, close to the margin, with one or more roundish dissections. There are usually no degenerative or posttraumatic changes. The history and frequent bilateralism tend to rule out trauma as the cause. In the authors' opinion, therefore, the term "osteochondrosis dissecans" should not be used for osteochondral fractures and their sequelae. A number of borderline cases are critically discussed.     

四氯偶氮苯在大鼠胆汁中的分泌和代谢

四氯偶氮苯（３,３’,４,４’ｔｅｔｒａｃｈｌｏｒｏａｚｏｂｅｎｚｅｎｅ,ＴＣＡＢ）和四氯氧化偶氮苯（３,３’,４,４’ｔｅｔｒａｃｈｌｏｒｏａｚｏｘｙｂｅｎｚｅｎｅ,ＴＣＡＯＢ）是在合成氯代或二氯代苯胺类除草剂时生成的污染废弃物。此类除草剂经...     

Prognosis and complications of open fractures]

This paper reviews records of Liestal Country hospital, AO Catalogue files and National Swiss Insurance Industry actuarials regarding open fractures. Specific regards are tended toward prognosis forecasting, complications and outcome assessments with respect to industrial "down time" resulting from bone infections and/or pseudarthroses. Evaluation of injuries is contingent upon the Gustilo Classification (1987) which bases prognosis on soft tissue preservation in open fracture injuries. We adhere to well accepted protocols which provide for adequate local primary débridement and stabilization of structural osseous components by means of appropriate fracture fixation. In addition, we have implemented protocols for the preservation of bony vascular elements along with sequential provisions for cancellous bone and soft tissue grafting. Outcome assessments on the range of cases reviewed confirm a traditional perspective that open fractures demonstrate considerably greater morbidity than closed fractures. However, by comparison with previous studies, the results of this series show positive progress toward optimal wound healing. While this more aggressive approach tends initially to be quite expensive, we believe initial costs to the carrier are justified by improved outcome, prognosis and industrial down time.     

Epithelioma cunicalutum developing in a neuropathic ulcer of leprous etiology

Summary Epithelioma cuniculatum is a distinctive tumor of the sole of the foot with characteristics of a low-grade carcinoma. A case is presented, the pertinent literature reviewed and its possibly frequent development in leprous patients discussed.

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Zusammenfassung Das Epithelioma cuniculatum stellt eine klar abgegrenzte Form eines low grade-Carcinoma dar. Ein Fall wird beschrieben, die Literatur zusammengefaßt und das möglicherweise gehäufte Auftreten bei Leprakranken diskutiert.

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Dedicated Professor Dr. E. Uehlinger on his 80th birthday