Effects of ω-conotoxin MVIIC on veratridine-induced cytotoxicity and cytosolic Ca oscillations

External Ca²⁺ entry through various Ca t+-channel subtypes is responsible for the large oscillations of the cytosolic Ca²⁺ concentrations, [Ca²⁺]_i, and cell death induced by veratridine in primary cultures of bovine chromaffin cells. Blockade by ω-conotoxin GVIA (GVIA) of N-type Ca²⁺ channels, by ω-agatoxin GIVA (IVA) of P-type Ca²⁺ channels, or by furnidipine of L-type Ca²⁺ channels did not afford cytoprotection. However, ω-conotoxin MVIIC (MVIIC), a wide-spectrum blocker of N-, P- and Q-type Ca²⁺ channels greatly protected the cells against the cytotoxic effects of veratridine. Furnidipine further enhanced the cytoprotecting effects of MVIIC. MVIIC but not fumidipine, markedly reduced the oscillations of [Ca²⁺]_i induced by veratridine in single fura-2-loaded chromaffin cells. The results suggest that Ca²⁺ entry through any of the different Ca²⁺ channel subtypes present in bovine chromaffin cells might be cytotoxic. They also support two ideas: (i) that wide-spectrum neuronal Ca²⁺ channel blockers (i.e. MVIIC) might be better cytoprotecting agents than more specific neuronal Ca²⁺ channel blockers (i.e., GVIA, IVA, furnidipine); and (ii) that combined Ca²⁺ channel blockers may provide greater cytoprotection than single compounds.     

2nd Congress of the International Society for Quality of Life Research Author Index

2nd Congress of the International Society for Quality of Life Research Author Index     

Stereochemistry of the major rodent liver microsomal metabolites of thecarcinogen dibenz[a,j]acridine

The major metabolites of the carcinogen dibenz[a,j]acridine formed in rodent liver microsomal preparations were trans-3,4-dihydroxy-3,4-dihydrodibenz[a,j]acridine (DBAJAC-3,4-DHD) and dibenz[a,j]acridine 5,6-oxide (DBAJAC 5,6-oxide) [Gill et al. (1987) Carcinogenesis 8, 425-431]. The enantiomers of DBAJAC-3,4-DHD were prepared from the separable diastereoisomeric esters with (+)-endo-1,4,5,6,7,7-hexachlorobicyclo[2.2.1]hept-5-ene-2-carboxyl ic acid (HCA). The absolute configuration of trans-3(R),4(R)-dihydroxy-1,2,3,4-tetrahydrodibenz[a,j]acridine was assigned by conversion to the bis[p-(dimethylamino)benzoate] and examination of the exciton coupling in its circular dichroic (CD) spectrum. The 3(R),4(R)-tetrahydrodiol was converted to DBAJAC-3(R),4(R)-DHD. The enantiomers of DBAJAC 5,6-oxide were partially resolved by chiral stationary-phase chromatography, and subsequent methoxide attack afforded two enantiomerically enriched isomeric ethers from each fraction. The structures of the two ethers from each enantiomer were determined, and from their 1H NMR spin-spin coupling between the H5 and H6 signals and the CD spectra of the ethers, the absolute configuration of the ethers, and hence the 5,6-oxides, was determined. The enantiomeric composition of the 3,4-dihydrodiol and 5,6-oxide formed as microsomal metabolites of rat liver preparations was 69% 3R,4R and 81% 5R,6S, respectively. When rats were pretreated with 3-methylcholanthrene (MC), these percentages were 70% and 5%, indicating a reversed stereochemical preference for oxide formation in the MC-induced preparation. Results are also presented for phenobarbitone-induced rat liver and mouse liver preparations.     

Cardiovascular risk factors in children and adolescents in Fuenlabrada: objectives, features of the population, design, participation, equipment, laboratory technics, and quality control

Fuenlabrada is at the present time the most industrialized town placed at the south are of Madrid. This population has some peculiar attractive characteristics from the epidemiologic point of view. Perhaps the most important is that the majority of its inhabitants are immigrant from other depressed rural areas of the country, with a low socio-economic and cultural level. The new conditions of life could have changed the life expectation and the causes of morbidity and mortality of this population. Between 1981 and 1984 we have studied the prevalence of cardiovascular risk factors in children and adolescents of its population, the relationships with cardiovascular risk factors and cardiovascular disease of the family and type of lactancy of the newborn. The variables studied were: height, weight, skin fold, blood pressure, lipids, lipoproteins, glycemia, uric acid and tobacco habit. The laboratory technics were standardized with serums of reference. The index of participation in the study of the required population was approximately of 80%.     

Bilateral massive osseous metaplasia in ovaries: “ovarian stones”

We report a case of bilateral ovarian ossifications with images that mimic stone formations. A 65-year-old woman presented with a 2-year history of pelvic pain. Computed tomographic scan and pelvic ultrasound identified an enlarged uterus with two calcified lesions interpreted as leiomyomas. Surgical exploration revealed two ovaries with a cystic appearance and stony hard areas. The cyst contents consisted of chocolate-colored material. The pathologic findings were compatible with benign bilateral ovarian endometriotic cysts with extensive ossification. The pelvic pain resolved completely after the surgery. Though the cause of this rare case remains unknown, recognition of cysts with a content of chocolate-colored material and pigment-laden histiocytes allowed us to make the diagnosis of bilateral ovarian endometriotic cysts with extensive ossification. Complete excision was the treatment of choice.     

Activity of human volunteer sera to candidate Plasmodium falciparum circumsporozoite protein vaccines in the inhibition of sporozoite invasion assay of human hepatoma cells and hepatocytes

Sera from human volunteers immunized with either synthetic peptide (NANP)3-TT or recombinant protein R32tet32 Plasmodium falciparum CS vaccines were tested in the inhibition of sporozoite invasion (ISI) assays using human hepatoma (HepG2-A16) cells or primary human hepatocytes. Sera or purified immunoglobulin (Ig) from volunteers who were completely protected against P. falciparum sporozoite challenge had higher ISI activity than sera from non-protected volunteers, or the highest titre endemic serum. However, Ig from protected and non-protected volunteers did not block sporozoite invasion of human hepatocytes, suggesting that P. falciparum sporozoites invade hepatocytes by mechanisms which differ from those concerned with invasion of HepG2-A16 cells.     

α-interferon potentiates epidermal growth factor receptor-mediated effects on human epidermoid carcinoma KB cells

The molecular mechanisms underlying the growth inhibition of human tumor cells induced by recombinant interferon-α (IFNα) are mostly unknown. It has been proposed that this effect could be related to down-regulation and/or impaired function of peptide growth factor receptors (PGF-Rs) in tumor cells exposed to IFNα. However, we have previously described that IFNα-induced growth inhibition of human epidermoid carcinoma cells is paralleled by up-regulation of epidermal growth factor receptor (EGF-R). Here we report that an increase in EGF-R synthesis is detectable after 3 hr of exposure to cytostatic concentration of IFNα in epidermoid KB tumor cells. In these experimental conditions IFNα does not depress and even potentiates EGF-R function. IFNα-treated KB cells retain sensitivity to the cytotoxic activity of the anti-EGF-R 225 monoclonal antibody (MAb), which acts through receptor blockade, and are sensitized to the growth-promoting effect of EGF. EGF-induced tyrosine (tyr) phosphorylation both of total cellular protein extracts and of the immunoprecipitated EGF-R is increased in IFNα-treated cells. We conclude that a cross-talk between IFNα and EGF occurs in KB cells since IFNα, at cytostatic concentration, potentiates the effects mediated by the EGF-R. © 1995 Wiley-Liss, Inc.     

A Late 'Migraine': The Only Symptom of an Intrasellar Aneurysm

The history of a 62-year-old woman affected by an intrasellar aneurysm is described. A migrainelike headache was, for many years, her only complaint.