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Biomedical subjects

C Díaz

Publications and source records attributed to C Díaz.

At least 127 records · Page 7Linked to original sources

p-Bromophenacyl bromide modification of Bothrops asper myotoxin II, a lysine-49 phospholipase A2, affects its pharmacological activities.

Modification of Bothrops asper myotoxin II, a lysine-49 phospholipase A2 variant, was carried out with p-bromophenacyl bromide. Modified toxin did not show changes in its charge and immunological properties but two of its pharmacological activities were modified. Myotoxic activity, measured by histology and by increment of creatine kinase levels in plasma of mice, was significantly reduced after toxin modification. In addition, liposome disruption activity was also significantly lower with the modified toxin both at 3 and 24 hr of incubation with the alkylating reagent. Some of the implications of these results on the structure-function relationship of myotoxins are discussed.

Acetophenones↗

Morphometric analysis of the vestibular complex in the rat.

The characteristics of the four major vestibular nuclei and accessory cell groups in the rat have been studied in serially cut horizontal sections. Camera lucida drawings of the vestibular nuclei and their neurons were made in these sections and subjected to a computerized image analysis. The dimensions (volume and length) and the number of cells of each vestibular nucleus were obtained, as well as morphometric parameters of their neurons (cross-sectional area, maximum and minimum diameter, and shape). These parameters were statistically analyzed by comparing the cell population from different nuclei and different parts of each nucleus. Of the major nuclei, the medial, which is the largest, has the greatest number of cells, its neurons being the smallest of all the nuclei, with the size of cells decreasing in a rostrocaudal direction. In contrast, the lateral nucleus contains the fewest cells but also the largest ones. Neurons of the superior and descending nuclei are of an intermediate size and number, with a rostrocaudal decrease in the size of the descending nucleus cells. In addition, minor nuclei are identified and described in their relationship to the other structures in the brain stem. The relevant aspects of the anatomical information in regard to functional roles are reviewed.

Animals↗

[Guidelines for the management of women with HIV infection].

During the second decade of AIDS the spread of this disease has encompassed most areas of the world. In Puerto Rico the epidemic has been different than in the mainland USA. Our initial cases were mostly associated to intravenous drug use and subsequently heterosexual transmission. Sexual transmission of HIV is the principal cause of AIDS for women in Puerto Rico. AIDS is also the principal cause of death in young women in Puerto Rico (ages 25-40). Therefore the counselling to women has to include the universality of the risk. Data from seroprevalence studies show a high prenatal seroprevalence (1%) in the San Juan Metropolitan Health Region. In view of the high prenatal seroprevalence, universal offering of HIV counselling and testing is recommended. Gynecologic evaluation is essential in the follow-up of women with HIV infection and should include frequent evaluations to determine the frequent occurrence of premalignant lesions in the cervix that may be associated to immunosuppression.

Acquired Immunodeficiency Syndrome↗

Isolation and characterization of basic myotoxic phospholipases A2 from Bothrops godmani (Godman's pit viper) snake venom.

Two basic myotoxic phospholipases A2 were purified to homogeneity from the venom of Bothrops godmani from Costa Rica by ion-exchange chromatography on CM-Sephadex. They have molecular weights of 14,300 (myotoxin I) and 13,400 (myotoxin II) and isoelectric points of 8.2 (myotoxin I) and 8.9 (myotoxin II). They behave as amphiphilic proteins in charge-shift electrophoresis and have similar amino acid compositions. Both toxins induce drastic myotoxic effects when injected in the gastrocnemius muscle of mice and induce release of peroxidase trapped in negatively charged liposomes. In addition, myotoxin I has high phospholipase A2 activity and is anticoagulant at doses higher than 0.3 microgram/ml, whereas myotoxin II has a very low phospholipase A2 activity and exerts anticoagulant effect only at concentrations higher than 50 micrograms/ml. Immunochemical data indicate that both toxins are immunologically related to Bothrops asper myotoxins, although B. godmani myotoxin II gives a stronger cross-reactivity when tested with antisera raised against B. asper myotoxins I and II.

Amino Acids↗

Neutralization of myotoxic phospholipases A2 from the venom of the snake Bothrops asper by monoclonal antibodies.

The neutralization of two myotoxic phospholipases A2 from the venom of Bothrops asper, myotoxins I and II, by two murine monoclonal antibodies is reported. The monoclonal antibodies, MAb-3 and Mab-4, recognize different epitopes of the toxin. Both antibodies completely neutralized myotoxic activity of myotoxin I and crude venom. MAb-3 also completely neutralized myotoxic activity of myotoxin II, a lysine-49 phospholipase A2 isoform, whereas MAb-4 neutralized this toxin only partially. MAb-3 neutralized myotoxin II at a molar ratio of 1:1, showing a higher efficiency than affinity-purified polyclonal antibodies. A dissociation of myotoxic and enzymatic activities of myotoxin I was observed with both monoclonal antibodies.

Animals↗

In vitro HRP-labeling of the fasciculus retroflexus in the lizard Gallotia galloti.

In order to test the usefulness of the in vitro HRP-labeling technique in the brains of small lizards, the fasciculus retroflexus was labeled in isolated brains of young specimens of the lizard Gallotia galloti by means of HRP applied with the tip of a micropipette located approximately midway along the descending course of the tract. Cells in the medial and lateral habenular nuclei were labeled retrogradely. Anterograde transport showed the course of the fasciculus retroflexus, first dorsoventrally into the paramedian prerubral tegmentum and then longitudinally into the isthmic nucleus interpeduncularis. Some fibers spread dorsally into the mesencephalic and isthmic tegmental fields. A substantial bundle continues caudally into nucleus raphe parvocellularis. Other fibers diverge rostral-wards from the point of inflexion of the fasciculus, coursing longitudinally in the medial forebrain bundle into the basal telencephalon. Some fibers course rostrally from the nucleus habenularis lateralis in the stria medullaris and could be followed to the dorsal septum.

Animals↗

Afferent connections of the habenular complex in the lizard Gallotia galloti.

Afferents to the habenular complex were studied by means of in vitro horseradish peroxidase retrograde labeling and anterograde control experiments in the lizard Gallotia galloti. The medial habenular nucleus was found to receive abundant afferent fibers from the nucleus of the posterior pallial commissure and the nucleus septalis impar. More restricted input comes from the nucleus eminentiae thalami and the nucleus of the stria medullaris. The lateral habenular nucleus is innervated by various fiber groups originating from the bed nucleus of the anterior commissure, the diagonal band nucleus, the lateral preoptic area, the anterior entopeduncular nucleus, the lateral hypothalamic and mammillary areas, the nucleus of the stria medullaris, the area tegmentalis ventralis and a scattered neuronal subpopulation in the large-celled dorsolateral nucleus of the dorsal thalamus. Habenulopetal fibers generally follow the stria medullaris, but hypothalamic, entopeduncular and dorsal thalamic afferents course through the dorsal peduncle of the lateral forebrain bundle in a transthalamic route. Mesencephalic ventral tegmental afferents ascend through the tractus retroflexus.

Afferent Pathways↗

[The palliative treatment of pancreatic cancer: percutaneous drainage versus surgical diversion].

In a retrospective study, the outcome of 56 patients with unresectable carcinoma of the exocrine pancreas undergoing two palliative operations (bypass surgery vs percutaneous transhepatic biliary drainage with endoprosthesis) for the management of biliary obstruction was evaluated. Morbidity and mortality were similar in the two groups. Postop hospital stay was 8 days for the intubated, and 15 days for operated patients (p less than 0.01). Although the symptom-free period was similar in both groups, intubated patients had a shorter period of poor-quality life.

Biliary Tract↗

[Changes in diastolic function in heart rejection: role of Doppler echocardiography].

In acute cardiac rejection, left ventricular diastolic function is altered. To study these abnormalities and their utility in cardiac allograft rejection, we studied 56 cardiac transplant recipients. All patients were assessed with endomyocardial biopsy and Doppler echocardiography done in the same day. A total of 163 Doppler studies were recollected. Cardiac transplant recipients were excluded during the early 6 weeks postoperative period. Totally, 100 biopsies were normal, 48 positive for mild rejection (Billingham Gde I-II) and 15 positive for moderate or severe rejection (Billingham Gde III-IV). Compared to negative biopsies, during acute rejection left ventricular wald thickness significantly increased (p < 0.05); isovolumic relaxation period and pressure half-time significantly decreased (p < 0.05, p < 0.001 respectively). Nevertheless, increase in peak early mitral flow velocity was only significantly associated with severe rejection (p < 0.001). Correlating only progressive shortening of isovolumic relaxation period parameter in the diagnosis of graft rejection, we forward a high sensibility (85%) and low specificity (57%). Thus, Doppler echocardiographic evaluation of left ventricular diastolic function provides a non-invasive tool for early detection of acute rejection monitoring after the early postoperative period.

Adult↗

Erythroid abnormalities in rheumatoid arthritis: the role of erythropoietin.

Erythroid alterations were studied in 136 patients with rheumatoid arthritis (RA). Anemia was present in 75 cases. A definite diagnosis was determined in 65. The most frequent anemia was that of chronic disease (ACD) (43 cases); 14 patients with ACD presented with moderate to severe anemia. Prevalence of deficiencies were also high (15 cases had iron deficiency anemia, IDA). Serum erythropoietin levels were different in patients with RA compared with a healthy control group (p < 0.00001). Serum erythropoietin was increased in ACD (49 +/- 28.8 U/l) with respect to both RA (38.6 +/- 12.7 U/l, p = 0.0036) and controls (18.2 +/- 7.6 U/l, p < 0.00001). Although hemoglobin (Hb) was similar in ACD and IDA, serum erythropoietin in ACD was lower than in IDA (p = 0.01). There was a negative relationship between Hb and serum erythropoietin in ACD (r = -0.42, p = 0.005). In conclusion, almost 50% of patients with RA have anemia and ACD is the most frequent. As serum erythropoietin in ACD is blunted, patients with moderate to severe ACD are possible candidates for erythropoietin treatment.

Adult↗

The effect of myotoxins isolated from Bothrops snake venoms on multilamellar liposomes: relationship to phospholipase A2, anticoagulant and myotoxic activities.

The effect of four myotoxins isolated from Bothrops snake venoms on the release of peroxidase trapped in large multilamellar liposomes was studied and correlated to their phospholipase A2, myotoxic and anticoagulant activities. The four myotoxins affected negatively-charged liposomes in a dose-dependent way, having no effect on positively-charged liposomes. Conditions that inhibited phospholipase A2 activity, i.e., substitution of calcium by EDTA, reduced liposome-disrupting activity of Bothrops asper myotoxin I and Bothrops atrox myotoxin, both of which have high phospholipase A2 activity, but did not affect the action of B. asper myotoxin II and Bothrops moojeni myotoxin II, which have extremely low phospholipase A2 activity. However, all myotoxins disrupted to some extent negatively-charged liposomes under conditions where phospholipase A2 activity was abolished. Since these toxins behave as amphiphilic proteins in charge-shift electrophoresis, it is suggested that membrane-disorganization is at least partially due to a non-enzymatic penetration and alteration of bilayers. There was no strict correlation between liposome-disrupting activity and myotoxicity in vivo. Thus, although both effects probably depend on the toxins' ability to disturb membranes, it is likely that variation in complexity between skeletal muscle plasma membrane and liposome bilayers are the basis for this difference. The anticoagulant effect seems to depend on the ability of the toxins to enzymatically degrade phospholipids, since only B. asper myotoxin I and B. atrox myotoxin prolonged the plasma recalcification time.

Animals↗

Skeletal muscle degeneration and regeneration after injection of bothropstoxin-II, a phospholipase A2 isolated from the venom of the snake Bothrops jararacussu.

A myotoxic phospholipase A2, named bothropstoxin II (BthTX-II), was isolated from the venom of the South American snake Bothrops jararacussu and the pathogenesis of myonecrosis induced by this toxin was studied in mice. BthTX-II induced a rapid increase in plasma creatine kinase levels. Histological and ultrastructural observations demonstrate that this toxin affects muscle fibers by first disrupting the integrity of plasma membrane, as "delta lesions" were the earliest morphological alteration and since the plasma membrane was interrupted or absent in many portions. In agreement with this hypothesis, BthTX-II released peroxidase entrapped in negatively charged multilamellar liposomes and behaved as an amphiphilic protein in charge shift electrophoresis, an indication that its mechanism of action might be based on the interaction and disorganization of plasma membrane phospholipids. Membrane damage was followed by a complex series of morphological alterations in intracellular structures, most of which are probably related to an increase in cytosolic calcium levels. Myofilaments became hypercontracted into dense clumps which alternated with cellular spaces devoid of myofibrillar material. Later on, myofilaments changed to a hyaline appearance with a more uniform distribution. Mitochondria were drastically affected, showing high amplitude swelling, vesiculation of cristae, formation of flocculent densities, and membrane disruption. By 24 hr, abundant polymorphonuclear leucocytes and macrophages were observed in the interstitial space as well as inside necrotic fibers. Muscle regeneration proceeded normally, as abundant myotubes and regenerating myofibers were observed 7 days after BthTX-II injection. By 28 days regenerating fibers had a diameter similar to that of adult muscle fibers, although they presented two distinctive features: central location of nuclei and some fiber splitting. This good regenerative response may be explained by the observation that BthTX-II does not affect blood vessels, nerves, or basal laminae.

Actin Cytoskeleton↗

Ultrastructural study of lamellar and nucleolus-like bodies in the harderian gland during postnatal development of the hamster (Mesocricetus auratus).

Membranous structures identified as lamellar bodies (LBs) and dense intracytoplasmic bodies referred to as nucleolus-like bodies (NLBs) have been found in the hamster Harderian gland during neonatal stages. Both structures appear between 8 and 12 postnatal days, coinciding with the beginning of secretory activity. LBs in males and NLBs in both sexes gradually decrease in number with further differentiation of the glandular cells. The morphological features of these cytoplasmic structures are described, and their origin as well as their possible functional significance are discussed.

Animals↗

Circadian changes in synaptic ribbons and spherules in pinealocytes of the Syrian hamster (Mesocricetus auratus).

In the present study, "synaptic" ribbons were studied morphologically and quantitatively in hamster pineal gland. The number of ribbons and spherules of hamster pinealocytes was counted over a 24-h period. The 24-h variations in the quantity of "synaptic" ribbons were found to parallel fluctuations in pineal melatonin concentrations. No significant circadian changes were observed for "synaptic" spherules, indicating different roles for these two structures.

Animals↗