In vivo potentiation of cis-diamminedichloroplatinum (II) antitumor activity by pretreatment with sparsomycin

The influence of protein synthesis inhibition by sparsomycin (Sm) on in vivo cisplatin activity has been studied on BALBc X DBA2: F1 mice bearing L1210 leukemia i.p. Sm alone at the dose range from 0.5 to 3.0 mg/kg did not significantly improve animal survival. Sm potentiated cisplatin activity only when given 3 or 6 h prior to cisplatin (P less than 0.001). Sm 0.5-1.5 mg/kg 3 h prior to cisplatin resulted in a significant prolongation of animal survival (P less than 0.001) and 66% cures in each group versus 0% due to cisplatin alone. Sm pretreatment decreased weight loss due to cisplatin suggesting that it probably is able to decrease cisplatin toxicity.     

In vitro proliferation of primary human head and neck squamous cell carcinomas evaluated by flow cytometry

In vitro proliferation of primary human head and neck squamous cell carcinomas was investigated using single cell suspensions and tissue explants of primary specimens and xenografts from 20 tumor specimens. The evaluations of the cells emerging in culture were performed with flow cytometry. Epithelial-like cells proliferated in serum-free medium, while no fibroblast-like cells were observed in culture. The epithelial-like cells could be subcultured several passages before senescence occurred. Conditioned medium or serum supplementation was necessary for a sustained outgrowth of malignant squamous cells as documented by flow cytometry. From a tumor line established in nude mice slowly proliferating tumor cells emerged. After 4-5 months in culture tumor cells seemed to be adapted to the culture conditions used. This resulted in a more consistent tumor cell proliferation. Early passage cultures from primary human head and neck squamous cell carcinomas are clearly difficult to obtain either from primary human specimens or from tumor lines established in nude mice.     

Histopathological effects of different therapy strategies in experimental sinus thrombosis

The optimal treatment for cerebral venous thrombosis is still under debate. The histological consequences of different treatments have not been systematically studied and may be of value in this debate. Thrombosis of the superior sagittal sinus was induced in rats by topical application of ferric chloride. Animals were treated 6 h after operation with subcutaneous injection of 450 IU/kg enoxaparin twice daily (n = 10), with 10 mg recombinant tissue plasminogen activator (rt-PA)/kg (n = 12), and with 6 mg abciximab/kg (n = 10). Eleven animals were treated with saline (controls), and four animals were sham-operated without thrombosis induction. Animals were killed on day 7. Coronal brain slices were stained with hematoxylin–eosin (HE) and against glial fibrillary acidic protein (GFAP), and factor VIII. Histology was quantified in parasagittal and temporal regions of interest. Compared with controls, counts of pyknotic neurons on HE stain were significantly lower in the enoxaparin group. Counts for GFAP-expressing astrocytes were highest in the enoxaparin (p < 0.001) and rt-PA (p < 0.05)-treated groups. Angiogenesis defined as factor VIII-expressing vessels was significantly (p < 0.01) higher in the enoxaparin and significantly lower (p < 0.01) in the rt-PA group compared with controls. In this animal model, we found histological differences related to the different treatments, which cannot be explained by recanalization and its speed alone.     

Modulation of placental alkaline phosphatase activity and cytokeratins in human HN-1 cells by butyrate, retinoic acid, catecholamines and histamine

The effects of butyrate and retinoic acid in combination with catecholamines or histamine on the HN-1 human head and neck squamous carcinoma cell line were investigated analysing cell proliferation, placental alkaline phosphatase (PLAP) activity, and relative cytokeratin content. Butyrate inhibited cell proliferation in agar, whereas retinoic acid induced a small inhibitory effect. Butyrate enhanced PLAP activity in a time related manner in contrast to retinoic acid, which had no significant effect. However, retinoic acid inhibited the efficacy of butyrate to induce PLAP activity. A synergistic enhancement of PLAP activity was demonstrated after treatment of butyrate pretreated cells with catecholamines or histamine. The beta-adrenergic antagonist propranolol partly inhibited the aforementioned enhancement of PLAP activity, whereas the alpha-adrenergic antagonist phentolamine further enhanced PLAP activity. Indirect labeling of keratins with a polyclonal antibody showed that cytokeratin content was enhanced by butyrate but not by retinoic acid. Further analysis of cytokeratin content using four monoclonal antibodies showed that labeling of cytokeratins (5 + 8) was increased by butyrate. PLAP activity could be modulated by a concerted action of either butyrate plus retinoic acid or butyrate plus catecholamines or histamine, indicating a possible role for PLAP in tumour cell proliferation.     

Relationship of purpose in life to grief experiences in response to the death of a signifcant other

This study examined the relationship of purpose in life to grief experiences in response to the death of a significant other. Forty undergraduates who had sustained the death of a loved one completed an information sheet, the Purpose in Life Test, and the Grief Experience Inventory. Bereaved persons who reported low purpose in life appeared to experience more anger than individuals with high purpose. This preliminary finding is linked to literature demonstrating an association between low purpose in life and emotion-focused coping; the finding is discussed in terms of working with bereaved clients.     

Uterine artery embolization for symptomatic fibroids.

OBJECTIVES: The aim of this study was to introduce uterine artery embolization (UAE) as an effective and safe treatment option in patients with symptomatic fibroids. METHODS: Sixty-one patients underwent UAE with a 3- and 12-month follow-up. RESULTS: The procedure was well tolerated in all patients with the following symptoms improving: heavy bleeding [90% (95% CI 80.21%; 95.4%)]; dysmenorrhea [median -4 (95% CI -5; -4)]; feeling of a mass [74% (95% CI 57.9%; 85.8%)]; abdomino-pelvic discomfort [88% (95% CI 75.5%; 94.9%)]; and deep dyspareunia [90% (95% CI 71.1%; 97.3%)]. Uterine volume decreased by a median difference of 188 cm(3) (95% CI 146.5; 236), which related to a median % reduction of 37.7% (95% CI 32.4%; 45%) at 12-month follow-up. Most (91%) patients were satisfied with the procedure and only minor complications occurred. CONCLUSIONS: Uterine artery embolization can be performed effectively and safely at centers with the necessary expertise and can be used with success in Africa.     

Photocatalytic degradation of cyanobacterial microcystin toxins in water

The microcystins are hepatotoxins produced by a number of cyanobacterial species (blue–green algae) in fresh water systems. The increasing eutrophication of natural waters has led to an increase in the incidence of algal blooms and the consequent increased risk of microcystin contamination of water resources. The removal of microcystins LR, YR and YA from contaminated water was investigated using an experimental laboratory-scale photocatalytic ‘falling film' reactor in which an oxygen purge, UV radiation and semiconductor titanium dioxide (TiO₂) catalyst were used to oxidatively decompose the microcystin pollutants. Preliminary studies, using algal extracts spiked into distilled water, indicated that the microcystins were rapidly decomposed in this reactor. The decomposition followed first order reaction kinetics with half-lives of less than 5 min with the reactor operating in a closed-loop mode. Reaction rates were strongly dependent on the amount of TiO₂ catalyst (0–5 g/l), but only marginally influenced by a change in gas purge from oxygen to compressed air. The use of lake water, rather than distilled water, showed that this process is feasible in natural waters, although increased levels of catalyst (up to 5 g/l) were required to achieve comparable decomposition rates.     

Pharmacology of 1-(3,4-dichlorobenzyl)-3,4,5,6-tetrahydro-2(1H)-pyrimidone, a novel antidepressant compound with antianxiety activity

1-(3,4-dichlorobenzyl)-3,4,5,6-tetrahydro-2(1H)-pyrimidone (I) was evaluated in selected pharmacological tests, and its activity was compared to that of some clinically useful psychotropic drugs. Based on the results, it is evident that I has a unique profile of antidepressant and antianxiety activities that are evident in the same dose range. The mechanism of its antidepressant activity is proposed to be similar to the tricyclic antidepressants, that is, inhibition of norepinephrine uptake. Neither I nor the tricyclic antidepressants possess monoamine oxidase-inhibiting activity. However, unlike the tricyclic antidepressants, I is devoid of any significant anticholinergic activity and presumably is free of anticholinergic side effects.