Search PubMed⌕ Search

Biomedical subjects

C M Gonzalez

Publications and source records attributed to C M Gonzalez.

25 records · Page 2Linked to original sources
PubMed1996

(S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16, 21-dimetheno-1H, 13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H)-d ione (LY333531) and related analogues: isozyme selective inhibitors of protein kinase C beta.

Protein kinase C (PKC) is a family of closely related serine and threonine kinases. Overactivation of some PKC isozymes has been postulated to occur in several diseases states, including diabetic complications. Selective inhibition of overactivated PKC isozymes may offer a unique therapeutic approach to disease states such as diabetic retinopathy. A novel series of 14-membered macrocycles containing a N-N'-bridged bisindolylmaleimide moiety is described. A panel of eight cloned human PKC isozymes (alpha, beta I, beta II, gamma, delta, epsilon, sigma, eta) was used to identify the series and optimize the structure and associated activity relationship. The dimethylamine analogue LY333531 (1), (S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16, 21-dimetheno-1H, 13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene++ +-1,3(2H)-dione, inhibits the PKC beta I (IC50 = 4.7 nM) and PKC beta II (IC50 = 5.9 nM) isozymes and was 76- and 61-fold selective for inhibition of PKC beta I and PKC beta II in comparison to PKC alpha, respectively. The additional analogues described in the series are also selective inhibitors of PKC beta. LY333531 (1) exhibits ATP dependent competitive inhibition of PKC beta I and is selective for PKC in comparison to other ATP dependent kinases (protein kinase A, calcium calmodulin, caesin kinase, src tyrosine kinase). The cellular activity of the series was assessed using bovine retinal capillary endothelial cells. Retinal endothelial cell dysfunction has been implicated in the development of diabetic retinopathy. Plasminogen activator activity stimulated by a phorbol ester (4 beta-phorbol 12,13-dibutyrate) in endothelial cells was inhibited by the compounds in the series with ED50 values ranging from 7.5 to 0.21 microM. A comparison of the PKC isozyme and related ATP dependent kinase inhibition profiles is provided for the series and compared to the profile for staurosporine, a nonselective PKC inhibitor. The cellular activity of the series is compared with that of the kinase inhibitor staurosporine.

Amino Acid Sequence↗
PubMed1981

Effect of prostaglandin F2 alpha on the bovine fetal ruminal wall in vitro.

Strips of rumen wall from bovine fetuses were incubated in an organ bath with prostaglandin F2 alpha (0.13 to 33.76 microgram/ml). The highest reactivity with a submaximal dose (17.03 microgram/ml) was observed in the period between 3.0 and 7.9 months of fetal age. A smaller response, but higher than in 1.0 to 2.9 months old fetuses, was observed in the 8.0 to 8.9 months fetuses. The period of the highest reactivity to prostaglandin F2 alpha coincides with the age of onset of papillary morphogenesis and the period of highest reactivity to autonomic and putative transmitter drugs.

Animals↗
PubMedDate not supplied

Toxicity to topical dimethyl sulfoxide in a pediatric patient with anthracycline extravasation.

Accidental extravasation of vesicant chemotherapy may cause important tissue injuries. Nowadays, the majority of authors propose topical dimethyl sulfoxide (DMSO), with or without local cooling, as the treatment of choise efor anthracyclines extravasation. No significant toxicity has been reported when DMSO is used as topical treatment. This report describes a case of local toxicity consisting of severe pain after its use in a pediatric patient. An illustration shows the extravasation area.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

Protein and gene expression of nitric oxide synthase isoforms I and III in the rat penile shaft.

Nitric oxide synthase (NOS) plays a key role in penile smooth muscle relaxation through the regulation of nitric oxide (NO). NO is a major neurotransmitter in the autonomic nervous system, and alteration of its activity has been implicated in erectile dysfunction. The objectives of this study were twofold: 1) to demonstrate and localize the NOS protein isoforms I and III in the normal rat penis, and 2) to identify and quantitate NOS I and III gene expression in the normal rat penis. The gene and protein product of NOS isoforms I and III are expressed in rat penile tissue. Protein expression of NOS I was confined primarily to neuronal tissue, while NOS III protein expression was identified primarily in both cavernosal smooth muscle and endothelium. The presence of both NOS I and III was confirmed in the penile shaft by Western blot. Quantitation of NOS I and III gene expression by reverse transcription-polymerase chain reaction revealed NOS III to be more highly expressed than that of NOS I in the rat penile shaft. NOS I and III protein and gene products are both expressed in normal rat penile tissue. Protein expression is localized primarily to neuronal tissue for NOS I, whereas NOS III is localized primarily to cavernosal smooth muscle and endothelium. NOS III gene expression is greater than that of NOS I in the normal rat penile shaft. These findings support the possibility that penile erection is regulated by different NOS isoforms released from neural, endothelial, and smooth muscle sources.

Animals↗