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Biomedical subjects

M Martinez

Publications and source records attributed to M Martinez.

At least 289 records · Page 16Linked to original sources

Lipids of the developing human retina: I. Total fatty acids, plasmalogens, and fatty acid composition of ethanolamine and choline phosphoglycerides.

The total fatty acid composition of the human retina was studied during early normal development and compared to that found in infancy and in adulthood. The retina of an infant undernourished prenatally and of two malnourished postnatally were also studied and compared to the normal values for the age. The fatty acid patterns of ethanolamine phosphoglycerides (EPG) and choline phosphoglycerides (CPG) were also studied. Total and ethanolamine plasmalogens (EP) were estimated by the aldehyde dimethyl acetal (DMA) content of total lipids and of EPG, respectively. After acid methanolysis, analyses of fatty acid methyl esters (FAME) and of DMA were effected by capillary GLC on a single 30 m long, SP-2330, capillary column. The main developmental fatty acid changes were an increase in 22:6 omega 3, 22:5 omega 3 and 20:3 omega 6 and a decrease in 20:4 omega 6. The 22:6 omega 3/20:4 omega 6 ratio increased in a very significant, parabolical way throughout development. In contrast to the brain, the proportion of ethanolamine plasmalogens decreased with maturation, whereas the ratio 18DMA/16DMA increased. The two postnatally malnourished infants had a very significant increase in retinal 22:5 omega 6, but only the child that had been fed on a very unbalanced omega 3/omega 6 diet since 25 weeks of gestation showed an important decrease in retinal 22:6 omega 3.

Aging↗

In vitro study of the aromatic hydroxylation of 1-methyltetrahydro-beta-carboline (methtryptoline) in rat.

The incubation of 1-methyltetrahydro-beta-carboline (1-MeTHBC) with hepatocytes isolated from 3-methylcholanthrene-treated rats led to formation of the 5-, 6- and 7-hydroxylated products. The hydroxylating activity was associated with the microsomal fraction as indicated by testing different subcellular fractions. The highest activity for hydroxylating 1-MeTHBC was found in liver which was about ten times as active as lung. Only a trace amount of hydroxylating activity was present in brain and kidney tissue. Analysis using chiral gas chromatography revealed an unequal abundance of enantiomers in all three products. The formation of the 5-, 6- and 7-hydroxylated products was confirmed in vivo by analysis of 24 h urine samples after intraperitoneal administration of 1-MeTHBC to 3-methylcholanthrene-treated rats.

Animals↗

Benzo[a]pyrene metabolism and induction of enzyme-altered foci in regenerating rat liver.

The metabolism of benzo[a]pyrene (BP) in regenerating rat liver and the induction of enzyme-altered foci (EAF) in the liver of partially hepatectomized rats, treated with BP and promoted with 2-acetylaminofluorene (2-AAF)/CCl4 was investigated. The aim was to examine factors that might be of importance for the tumorigenicity of BP in the regenerating rat liver, such as cytochrome P-450 activity and glutathione levels. In regenerating rat liver, obtained 18 h after partial hepatectomy (PH), the amount of microsomal cytochrome P-450 was reduced by 20% whereas the level of glutathione was elevated by 15% and the cytosolic glutathione transferase activity towards chlorodinitrobenzene and (+/-)-7 beta,8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydro-BP (BPDE) was unaffected. Microsomes from these animals had a reduced capacity to activate (-)-trans-7,8-dihydroxy-7,8-dihydro-BP (BPD) to DNA-binding products but the pattern of BP metabolites was similar to that observed with control rat liver microsomes. Treatment of rats with 3-methylcholanthrene (MC, 50 mg/kg body wt.) increased cytochrome P-450 levels and glutathione transferase activity towards both substrates. Regenerating livers from these animals retained their cytochrome P-450 level and enzymatic activity towards BP and BPD. Regenerating rat liver microsomes from MC-treated animals were about 35 times more efficient in activating BPD than microsomes from uninduced, partially hepatectomized animals. Intraperitoneal administration of BP (50 mg/kg body wt.) 18 h after PH induced EAF in rats subsequently promoted with 2-AAF/CCl4. Pretreatment of rats with MC 66 h before PH and 84 h before BP administration, increased the number of EAF. In accordance with results by Tsuda et al. (Cancer Res., 40 (1980) 1157-1164), these studies demonstrate that BP is tumorigenic in regenerating rat liver, despite a reduced ability of the liver to activate this compound. Furthermore, MC, an inducer of certain cytochrome P-450 species ("aryl hydrocarbon hydroxylase"), potentiates the effect of BP.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

Composition and synthesis of polyunsaturated fatty acyl groups in the embryonic brain of the trisomy-16 mouse.

The trisomy-16 (T-16) mouse is considered to be a promising model for human trisomy-21 (T-21) (Down's syndrome, DS). Therefore, the fatty acyl (PUFA) compositions of phosphoglycerides in embryonic brains (days E-17 and E-18) of T-16 mice have been compared with those of balanced heterozygotic embryos from the same litters, in order to determine whether similar abnormalities are present as have been found in foetal DS brain (Brooksbank et al., 1985, J. Neurochem. 44, 869-874). The analyses revealed that the ratio of (n-3) to (n-6) PUFA was significantly increased in ethanolamine (EPG) and in choline phosphoglycerides, as it is in EPG in the foetal T-21 brain. However, the abnormality was not so marked in the murine as in the human trisomy, and the (n-3)/(n-6) ratio in EPG was primarily elevated on account of decreased proportions of 20:4(n-6) and 22:4(n-6), there being no significant increase in (n-3) PUFA. The PUFA composition of the phosphoglycerides of the corresponding trisomic and balanced placentae was also determined, but no relevant differences could be discerned between the genetically different tissues. As 6-desaturase, the rate-limiting enzyme system in PUFA synthesis, reacts more readily with (n-3) than with (n-6) substrates, the shift in (n-3)/(n-6) ratio of PUFA might be related to an alteration in 6-desaturase activity in trisomy. Comparison of the specific activity of 6-desaturase in fresh brain homogenates of T-16 embryos with those from balanced litter-mates revealed, however, no differences.

Animals↗

Undergraduate teaching of oncology in Argentina.

Cancer is a public health problem in Argentina, and the role of the country's physicians in the fight against this disease is very important. Whether they are general physicians or specialists, including clinical oncologists, they must have basic knowledge and permanent updating in oncology. Unfortunately, the teaching of oncology is deficient in this country, the deficiencies being already noticeable at the undergraduate level where the teaching is incomplete and dispersed. In order to ascertain the level of oncologic information which medical students about to graduate had acquired, 15-hour courses were organized in 1983 to 1984 for students of the Universities of Buenos Aires, La Plata, and Del Salvador. The participants had to fill in a questionnaire of 50 questions of increasing complexity before and after the course. The comparison of both inquiries clearly showed the usefulness of the course, particularly regarding cancer control, early diagnosis, treatment, and curability. The overall error decreased by 50% after the course. However, some erroneous ideas still existed and it became evident that certain of the subjects must be studied in greater depth.

Argentina↗

Reactogenicity and antigenicity of rhesus rotavirus vaccine (MMU-18006) in newborn infants in Venezuela.

The reactogenicity and antigenicity of the rhesus rotavirus vaccine, strain MMU18006, developed at the Laboratory of Infectious Diseases (National Institute of Allergy and Infectious Diseases, National Institutes of Health) were examined in a double blind, placebo-controlled study of 40 newborn infants in Caracas, Venezuela. The children were observed for the first few days after birth in the hospital nursery and by home visits for 10 days after vaccination to detect any adverse reactions. No reactions could be attributed to the vaccine. Serologic responses to the vaccine were evaluated in paired sera obtained at birth (cord blood) and 4 weeks after vaccination. Serologic responses to the vaccine were not observed by complement fixation, neutralization or a rhesus rotavirus VP7 epitope-specific competition assay. However, such responses were found in 9 of 14 tested infants by an immunoglobulin A-specific enzyme-linked immunosorbent assay. Seventeen of the 20 vaccinees also shed rhesus rotavirus vaccine in stool during the postvaccination period.

Antibodies, Viral↗

The potential of antiestrogens as centrally-acting antihostility agents: recent animal data.

Recent studies suggest that motivations for certain forms of masculine behavior including social aggression are mediated by central estrogen receptors. Two studies using antiestrogens in rodent species were performed. Intact male LH rats were given Tamoxifen or vehicle for 4 or 8 days. The three possible pairings were videotaped for 60 min. Intact male OF1 mice were given CI-680 or vehicle over 25 days. Similar pairings were carried out but some CI-680 or vehicle animals were paired with anosmic opponents. Encounters were videotaped for 10 min. In both experiments evidence was obtained that the antiestrogen markedly reduced time allocated to offense. Any variations in defense were a consequence of the level of attack to which animals were subjected. Neither compound greatly influenced the androgen-dependent sex accessory glands. Antiestrogens consequently have potential as antihostility agents in some forms of attack.

Aggression↗

Studies on the effects of the antiandrogen cyproterone acetate on social encounters between pairs of male mice.

An attempt was made in two experiments to reinvestigate the effects of the antiandrogen cyproterone acetate (CA) on mouse social behavior in a variety of ethologically-assessed paired encounters. The data confirm that CA reduces offense (threat and attack) in animals when both subjects receive the material but that CA has no such action in other pairings. This suggests that CA's major suppressive effect on "hostility" is expressed in mice via a reduction in "attack-promoting" pheromone production. Indeed, there was evidence in the more chronic study that CA, could augment (via a central mechanism?) offense in subjects paired with docile anosmic opponents. Changes in defense were largely responses to variations in the degree of attack to which animals were subjected. The antihormone also had actions on other aspects of behavior including sexual activity, social investigation and immobility in such tests. CA had a potent suppressive action on the weights of sex accessory glands. The data do not suggest that CA can be used as a specific antihostility agent.

Androgen Antagonists↗

Increased stability of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene through interaction with subcellular fractions of rat liver.

The rate of hydrolysis of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene (BPDE) to tetrahydroxy derivatives (tetrols) in the presence of various subcellular fractions of rat liver was investigated. Microsomes and nuclei increased the half-life of BPDE in a concentration-dependent manner whereas cytosol had no such effect. The presence of 1 mg microsomal protein/ml increased the half-life of BPDE from 4 to 60 min at 22 degrees C and from 1.5 to 20 min at 37 degrees C. Nuclei equivalent of 500 micrograms DNA/ml increased the half-life from 1.9 to 3.6 min at 37 degrees C. Liposomes prepared from microsomal lipids mimicked the effect of microsomes indicating that BPDE is stabilized primarily by interacting with lipids. The significance of these interactions for the stability of BPDE in an intact cell system was evaluated by using isolated hepatocytes. In these cells the half-life of BPDE was substantially shorter (1 min at 5 X 10(6) cells/ml) than in buffer (3 min). However, hydrolysis of BPDE to tetrols was a minor reaction (less than or equal to 3% of added BPDE at a cell density greater than or equal to 5 X 10(6) cells/ml) and the main route of elimination (greater than or equal to 75%) was through conjugation with glutathione.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

Hemoglobin C in association with hereditary persistence of fetal hemoglobin.

Hemoglobin C and hereditary persistence of fetal hemoglobin (HPFH) are an uncommon combination of hemoglobinopathies. Several tests are needed to verify this condition, among them hemoglobin electrophoresis and Kleihauer-Betke staining of a peripheral blood smear. Family studies are useful in delineating the genetics of the hemoglobinopathy but could not be performed in our case. In more confusing cases or with an unusual subtype, more extensive testing may be required. HPFH, by itself, is without clinical manifestations. It may be confused with other conditions; therefore, its presence in patients with hematologic symptoms requires more precise definition of the hemoglobin abnormality.

Adult↗

Myelin in the developing human cerebrum.

In order to ascertain the true composition of human myelin at the earliest stages of development and to shed some light on the controversial results published to date, the lipid and protein composition of myelin from unfrozen cerebrum of very young infants was compared to the values obtained later in development and to those obtained by other investigators using frozen human brain. The effect of 3 different procedures of myelin isolation, as well as varying periods of storing the brain in frozen state, were tested on the final composition of myelin. All myelin preparations were of a very high degree of purity, and the lipid composition changed very little either with age or by varying the method or the time of storage of the brain. Protein composition, on the other hand, changed drastically after freezing the brain for increasing periods, and the percentage of myelin basic protein (MBP) decreased to one-third of its original value after about a year of brain storage. However, when myelin was isolated from unfrozen brain immediately after autopsy, very high values of MBP were obtained, even in newborn cerebral myelin, which was quite mature from a morphological as well as from a biochemical point of view. These data reveal that the developmental changes of human myelin are much more subtle than has previously been thought.

Cell Fractionation↗

Studies on the further activation of benzo[a]pyrene diol epoxides by rat liver microsomes and nuclei.

The syn- and anti-diastereoisomers of trans-7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) were further metabolized by rat liver microsomes obtained from 3-methylcholanthrene(MC)-pretreated rats and NADPH to reactive intermediates, presumably 1,7,8- and 3,7,8-trihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrenes (triol-epoxides), that bound to macromolecules or decomposed to products consistent with pentahydroxy derivatives of benzo[a]pyrene (BP-pentols). Three major metabolites of syn-BPDE and four major metabolites of anti-BPDE were isolated by high performance liquid chromatography and characterized by spectroscopic techniques. When fluorescence spectroscopy was employed all metabolites exhibited very similar spectral properties and showed substantial shifts in excitation and emission maxima to longer wavelengths when measured under alkaline conditions, consistent with the presence of a phenolic hydroxyl group. Furthermore, the spectral properties of the metabolites from syn- and anti-BPDE were similar to those of 1-hydroxypyrene. Previous data from this laboratory together with the data presented in this study thus strongly suggest that further metabolism of BPDE involves hydroxylation at the 1- and 3-positions to yield the corresponding triol-epoxides and various BP-pentols. The pentols could also be formed by incubating tetrols derived from syn- and anti-BPDE with microsomes and NADPH. However, the rate of formation of pentols from the BP-tetrols was much slower than the rate of further metabolism of BPDE. Accordingly, the major route of BP-pentol formation is likely to be via the intermediate formation of triol-epoxides. Isolated liver nuclei from MC-pretreated rats were also found to catalyze the activation of anti-BPDE in presence of NADPH to reactive intermediates. This resulted in a substantial increase in binding to histone and non-histone proteins, with a concomitant decrease in binding to DNA. No qualitative change in the distribution of DNA-bound products of anti-BPDE could be demonstrated as a result of the further metabolism of anti-BPDE.

Animals↗

[Curietherapy of palpebral epithelioma with iridium-192. Method and results apropos of 192 cases treated at the Claudius-Regaud Center].

Authors report a series of 192 eyelid epithelial tumors (187 patients) treated by curietherapy (192 iridium) at the Centre Claudius-Regaud, from January 1977 to December 1982. Curietherapy is an interstitial radiotherapy technique which inserts radio-active lines directly in the epithelial area. The first part of treatment consisted in using disposable vascular catheters as after loading procedure. In 90% of the cases, lesions were either on the lower lid or on the inner canthus. Tumors were mainly of basal cell type (77%). One thousand forty one tumors occurred in untreated patients: treatment was made for local recurrences in 51 cases. The control rate was 97% (186/192). Six recurrences were all observed in basal cell carcinoma. Four of them were cured by a second curietherapy, the two others needed a large surgical enucleation followed in one case by external radiotherapy. Late side effects essentially were functional and ocular. Functional side effects (19% of the series) consisted in eyelid hole reduction (5%), epiphora stenosis (6%), ectropion (4%) and loss of substance (4%). Ocular complications (3% of the series), were ulcerated cornea (one case) hypertrophic conjunctivitis (one case), iatrogenic cataract (two cases) and enucleation for recurrence (two cases). Iridium 192 curietherapy allowed a high local control rate. The best results were seen in untreated patients. Iatrogenic cataract eventually would be avoided by the use of lead contact lenses (recent utilisation not included in this series).

Adult↗