The role of quinone reductase (NQO1) and quinone chemistry in quercetin cytotoxicity.

The effects of quercetin on viability and proliferation of Chinese Hamster Ovary (CHO) cells and CHO cells overexpressing human quinone reductase (CHO+NQO1) were studied to investigate the involvement of the pro-oxidant quinone chemistry of quercetin. The toxicity of menadione was significantly reduced in CHO+NQO1 cells compared to wild-type CHO cells, validating the NQO1-overexpression in the CHO+NQO1 transfectant. Quercetin inhibited the proliferation of wild-type CHO and CHO+NQO1 cells to a similar extent without affecting cell viability, indicating that NQO1 enrichment of CHO cells did not provide increased protection. On the other hand, inhibition of NQO1 in both types of cells by dicoumarol significantly potentiated the inhibitory effect of quercetin on cell proliferation, revealing the role of NQO1 in cellular protection against quercetin. Altogether, these results can be explained by the hypothesis that both wild-type CHO and CHO+NQO1 cells contain sufficient NQO1 activity for optimal protection against the pro-oxidant effect of quercetin on cell proliferation. The results also point at a cellular NQO1 threshold for optimal protection against quercetin. This NQO1 threshold seems to be in the range of NQO1 activities already present in various tissues.     

Role of aminophylline and allopurinol in the reformation of peritoneal adhesions

The role of aminophylline in the re-formation of peritoneal adhesions was considered in 23 rats. Since the adhesions were obtained, the animals were subsequently divided into three groups, the first one containing seven units, the others containing eight animals each. During the four days prior the surgery, allopurinol at the dose of 50 mg/kg/die was added to the regular ground laboratory chow in the animals of the second group; aminophylline at the dose of 40 mg/kg/die was administered four hours and immediately prior the surgery, to the animals of the third group. The adhesions that we observed, were graded and evaluated assigning them a score. At the moment of the lysis of adhesions, we observed the score of 2.71 +/- 1.11 in the first group, 3.12 +/- 1.13 in the second group, and 2.75 +/- 1.03 in the third one. Matching each group one another no statistically significant difference was found. At the end the experiment, we observed a score of 3.71 +/- 0.49 for the adhesions in the first group, 2 +/- 0.75 in the second group, and 3.87 +/- 0.35 in the third one. Matching these scores with those observed at the moment of their lysis, they appeared significantly higher in the animals of the first group (p less than 0.02) and of the third group (p less than 0.05), but they were lower in the second group (p less than 0.05). Such results indicate that the re-formation of peritoneal adhesions following their lysis is constant, that allopurinol decreases the intensity of the process, while aminophylline increases it.     

Tubular epithelium culture from nephronophthisis-affected kidneys: a new approach to molecular disorders of tubular cells

Abnormalities of tubular membrane structure and composition have been proposed as the primary defect in nephronophthisis (NEF). In order to characterize the protein composition of tubular cells in NEF, in vitro methods were developed to culture and propagate tubular cells obtained from biopsy fragments. Accordingly, microdissected cortical slices (1 x 3 mm) were first digested with collagenase and DNAse and then grown in RPMI medium supplemented with 10% NU serum and conditioned serum deriving from 3T3 cultures. At confluence, cultured cells from NEF showed characteristics which were typical of normal tubules, i.e. presence of cytokeratin and positivity for succinic dehydrogenase and alkaline phosphatase stainings, and presented no morphological alterations compared to cultured cells from normal tubular epithelium. Moreover, no difference was observed for fibronectin, collagen IV and laminin stains. Analysis by two-dimensional electrophoresis of cellular extracts revealed several changes in protein composition of NEF, the main one being the decrease in NEF cells of a polypeptide with a molecular weight of 120 kD and a pI of 4.8; this polypeptide was a constant finding in normal kidneys. These observations demonstrated that human tubular epithelial cells can be successfully cultured from very small biopsy fragments, which represents a new approach to the study of molecular disorders involving tubular cells in inherited disease. Cultured cells from NEF maintain the same morphological, immunological and cytochemical characteristics as normal tubular cells, but present a few alterations in polypeptide composition which may have pathogenetic relevance. A more careful analysis of these alterations is needed to define the molecular disorder(s) involving the tubule in NEF.     

A Case of Hypopigmented Mycosis Fungoides in a Young Caucasian Boy

Abstract: Hypopigmented mycosis fungoides is a variant of mycosis fungoides characterized by the presence of hypopigmented patches as the sole manifestation of the disease. It has been described aimost always in young black or dark-skinned patients. The only white patient described was a 64-year-oid woman who not oniy had hypopigmented lesions, but also nodular lesions with lymphadenopathy. We describe hypopigmented lesions arising in a white boy 12 years of age, born in northern Italy, without any foreign ancestors. The microscopic alterations, with epidermotropism, the immunoiogic markers, the negativity of T-cell receptor gene rearrangement, and the good response to PUVA therapy correspond to the main findings in black patients with this disease. Long-term follow-up of these patients is important to obtain better knowledge of the natural history of the disorder, Hypopigmented mycosis fungoides must now be included in the differential diagnosis of hypopigmented macular lesions not only in black or dark-skinned patients but also in white patients.     

Cystic fibrosis presenting with bilateral facial palsy.

A 15-week old male infant presented with bilateral lower motor neuron facial palsy of unknown cause. Subsequently his growth deteriorated and he developed progressively worsening cough and wheeze. A diagnosis of cystic fibrosis was confirmed and hypovitaminosis A detected. Improvement of the facial palsy was noted following standard management of cystic fibrosis including vitamin A supplementation.     

Antiepileptic drug toxicity: Definition and mechanism of action

A detailed review of the adverse reactions of anticonvulsants is given, focusing on the definitions of drug toxicity, sources of information, patterns of durg utilization, pharmacokinetic variables and different mechanisms of action. The information available in the literature provides a wide spectrum of drug toxicity with no attempt at a practical definition of the reported events. This favors uncertainty among practising physicians, who are led to use the individual items with different attitudes. Suggestions are given for the evaluation, prevention and treatment of anticonvulsant drug toxicity.

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Sommario La presente è una revisione critica dei diversi aspetti della tossicità dei farmaci antiepilettici. L'analisi della letteratura è condotta con particolare riferimento alle diverse fonti di informazione, ai pattern di utilizzo dei singoli principi attivi, ai dati farmacocinetici ed ai meccanismi di azione farmacologica sottostanti. L'ampio panorama che ne deriva non consente una definizione pratica degli effetti indesiderati degli anticonvulsivanti. Ciò determina incertezza e confusione nella pratica medica, con conseguente diversità di comportamenti. La rassegna si conclude con la presentazione di alcuni suggerimenti pratici per la valutazione, la prevenzione ed il trattamento della tossicità da anticonvulsivanti.

     

Synthesis and Ca-antagonist activity of some benzhydryl derivatives

The preparation of a series of benzhydryl derivatives is described. Their activities as Calcium-antagonists were evaluated on the taenia coli of the guinea-pig. These new compounds show lower activities as Ca-antagonists than Cinnarizine.