Calcium signals in cell lines derived from the cerebral cortex of normal and trisomy 16 mice.

We established two immortalized cell lines from cerebral cortex of normal (CNh) and trisomy 16 (CTb) mouse fetuses, an animal model of human trisomy 21. Those cells loaded with the fluorescent Ca2+ dyes, Indo-1 and Fluo-3, exhibited increments of intracellular Ca2+ ([Ca2+]i) in response to external glutamate, NMDA, AMPA and kainate. CTb cells exhibited higher basal Ca2+ concentrations and had higher amplitude and slower time-dependent kinetics in the decay than CNh cells, suggesting an impaired Ca2+ buffering capacity in the trisomy 16-derived cell line. Nicotine also induced increments of [Ca2+]i. The CTb cell line could represent a model for studying cellular alterations related to Down syndrome.

Osteopoikilosis and chondrocalcinosis.

Osteopoikilosis is a benign and rare disorder characterized by abnormal calcium phosphate deposition in the articular cartilage. It usually is an incidental radiologic finding. Chondrocalcinosis is characterized by calcium pyrophosphate deposition in the articular cartilage. Both diseases can be asymptomatic. We describe some radiographic features that distinguish osteopoikilosis from other similar conditions and report a young female patient with osteopoikilosis associated with chondrocalcinosis. To the best of our knowledge, this is the first time these processes have been found in the same patient.

Proteinase inhibition of fish muscle enzymes using legume seed extracts.

Seed extracts from indigenous and introduced legumes were prepared and used to search for inhibitors of fish muscle proteinases. Fish flesh extracts were prepared from samples of Merluccius productus (Pacific whiting or merluza) obtained off the Oregon coast and in the Gulf of California, respectively. The proteinase activity in the fish muscle for the Pacific whiting was the highest, followed by parasitized merluza. The lowest proteinase activity was for the nonparasitized merluza. Six out of 12 seed extracts reduced the proteinase activity from the fish flesh by more than 50%. The reduction of enzyme activity was higher for samples of fish flesh extracts from the Gulf of California than for the Oregon samples. Seed extracts also reduced the proteinase activity of commercial serine and cysteine proteinases such as trypsin, chymotrypsin, and papain. This inhibitory capacity was maintained even after heating the seed extracts to 90 degrees C for 15 min. Several seed extracts show promise for use as proteinase inhibitors during production of surimi, the intended commercial product of massive fisheries such as Pacific whiting or merluza.

New 4-alkyl-1,4-dihydropyridines: evaluation of photostability and phototoxic potential.

The photostability and phototoxic potential of two new 4-alkyl-1,4-dihydropyridines (PCA-4230 and PCA-4248) were investigated. When these 4-alkyl-1,4-dihydropyridines were irradiated with a multilamp photoreactor (band centred at 350 nm), both exhibited a slow photodegradation showing first-order kinetics. The photodegradation rate constants were 0.37 h-1 for PCA-4248 and 0.39 h-1 for PCA-4230 in oxygenated conditions. The photodecomposition was slower for both drugs in the absence of oxygen. In order to evaluate the phototoxicity induced by these drugs, red blood cells and Hep-2 (human laringo carcinoma cell line) were irradiated using a minisolarium, which emits UVA radiation (350-390 nm). The results showed that PCA-4248 and PCA-4230 did not exhibit a phototoxic effect in the two models tested.

Lipid peroxidation and loss of potassium from red blood cells produced by phototoxic quinolones.

Alterations of the cationic permeability of red blood cell membranes induced by the photosensitiser nalidixic acid were demonstrated by evaluating the potassium loss from intact erythrocytes. The results show that an increase in intracellular potassium efflux, precedes the photohemolysis induced by nalidixic acid. The addition of a nonpermeable osmotic solute, such as sucrose, inhibited photohemolysis but not the potassium loss, indicating a colloid osmotic lysis. Lipid peroxidation induced by nalidixic acid and other photosensitiser quinolones (oxolinic acid and rosoxacin) was time irradiation-dependent. Although rosoxacin was the most photoperoxidative, none of the three quinolones studied produced significant lipid peroxidation. However, of the three quinolones studied, only rosoxacin considerably diminished the percentage of the cholesterol extracted from red blood cell membranes. It is postulated that the increased cation permeability induced by nalidixic and oxolinic acids cannot be attributed to cholesterol oxidation nor to lipid peroxidation; a more probable mechanism is photo-oxidation of amino acid residues of the membrane proteins. However, the lysis induced by rosoxacin is caused by photo-oxidation of cholesterol, not excluding other cellular targets.

Phototoxicity induced by nalidixic and oxolinic acids: decrease in cell survival of chick embryo fibroblasts and Hep-2 cells.

The phototoxic effects of nalidixic and oxolinic acids were evaluated in two types of cultured cells: chick embryo fibroblast and Hep-2 (human laryngo carcinoma cell line). In order to evaluate the phototoxicity induced by nalidixic and oxolinic acids, both cell types were irradiated for 5 min in the presence of each drug. The results showed an inverse relationship between cell survival and the concentration of the drug added to the culture medium. The concentrations of nalidixic and oxolinic acids necessary to induce a phototoxic effect were in the range of therapeutic blood levels. Both chick embryo fibroblasts and Hep-2 cells were more sensitive to the phototoxic effect induced by nalidixic acid than oxolinic acid.