Biomedical subjects

R Ochoa

Publications and source records attributed to R Ochoa.

At least 37 records · Page 2Linked to original sources

PubMed1996

[Changes in molecular forms of sex hormone binding globulin during menstrual cycle and menopause].

Sex hormone binding globulin (SHBG) is a glycoprotein that transports mainly androgens and estrogens regulating the amount of free and bound hormone which in turn plays a role in the metabolic balance. It is also known that estrogens increase the hepatic production of SHBG which circulates in various molecular forms containing different amounts of sialic acid as the main component of carbohydrates. In the present work we studied physiological variations of molecular forms of SHBG during the normal menstrual cycle and the menopause. During the follicular phase the form 54 KD was the predominant variant, in the periovulatory period was isomers 90 KD, and during the luteal phase corresponded to both 54 and 90 KD. In the menopause dimeric form of 90 KD corresponded to the major proportion and was present a higher molecular forms of 115-135 KD. Following estrogen therapy the chromatographic profile changed as to that observed during the menstrual cycle. Important changes in the proportion of sialic acid were observed in each of the phases of menstrual cycle and following estrogen replacement. And increase in the amount of sialic acid corresponded to higher estrogen concentrations. It is concluded that SHBG concentrations varies during the menstrual cycle according the estrogen levels which in addition regulates the proportion of molecular forms and sialic acid containt.

Adult↗

PubMed1996

[Validation of a ultramicroELISA for detecting antibodies against hepatitis B surface antigen].

The results of a validation study of the ultramicroanalitical assay for the detection of antibodies against the hepatitis B surface antigen (UMELISA anti-HBsAg), which was carried out by comparing the results obtained with the Hepanostika anti-HBsAg, commercial diagnosis kit are presented. For this purpose, sera from the clinical assays of the Cuban recombinant vaccine against hepatitis B were used. With the first sera group (n = 30) it was obtained, 93.1% of sensitivity, 98.5% of specificity and a concordance of 94.3%. The correlation coefficient showed a similar trend of the results (p < 0.01) and no significant differences were found in the average geometrical titre (TPG) between both assays (p > 0.05). With the second group (n = 100), whose assays were carried out at the "Pedro Kouri" Institute of Tropical Medicine (PKI) and at the Immunoassay Center (IAC) simultaneously, it was observed a sensitivity of 96.25% in both centers, a specificity of 75% at the PKI and of 90% at the IAC, and a coincidence of 92% and 95%, respectively. The correlation coefficient presented similar values and there were no significant differences between the TPG obtained by the two methods (p > 0.05). The results attained show in general the validity of the new assay and the feasibility to put it into practice either for following up the infection, or for carrying out clinical assays of vaccine evaluations.

Enzyme-Linked Immunosorbent Assay↗

PubMed1995

Tirilazad mesylate--effects of the 21-aminosteroid on the lymphoid system of laboratory animals: a comparison with the glucocorticoid methylprednisolone.

Four-week toxicity studies with the 21-aminosteroid tirilazad mesylate were conducted in Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys to support development of the drug for use in various clinical syndromes of injury to the central nervous system of humans. As the immune system is involved in many of the obvious side effects of glucocorticoids used currently for this indication, particular attention was directed to the lymphoid system; results were contrasted with similar data from studies with methylprednisolone, a classical glucocorticoid. Administration of tirilazad mesylate to rats, dogs and monkeys for 4 weeks had no effects at the highest doses tested on parameters assessed, including absolute peripheral blood lymphocyte counts, thymus or adrenal weights, circulating levels of cortisol, or lymphocyte proliferation response to phytohemagglutinin-P. Germinal centers in lymphoid tissues from dogs given high doses of tirilazad contained small numbers of macrophages with vacuolated cytoplasm but no other changes; lymphoid tissues in rats and monkeys given tirilazad were morphologically normal. Administration of methylprednisolone for a similar duration in rats and dogs at high dose levels was associated with increased death rates due to bacterial infections, markedly decreased peripheral blood lymphocyte counts and weights of thymus and adrenal glands, and prominent lymphoid atrophy as well as decreased circulating levels of cortisol. Female dogs infused for 10 days with a high dose of methylprednisolone had depression of the in vitro proliferation response of peripheral blood lymphocytes to phytohemagglutinin-P.

Animals↗

PubMed1995

Elevation of activity of creatine phosphokinase (CK) and its isoenzymes in the newborn is associated with fetal asphyxia and risk at birth.

OBJECTIVE: To investigate the relationship of creatine phosphokinase and its isoenzymes with fetal asphyxia and risk at birth. METHODS: Thirty-five pregnant women with high-risk pregnancy were studied. RESULTS: In 21 patients, fetal distress was diagnosed by interpretation of the fetal heart rate tracing (FHR). The remaining 14 women, having normal fetal cardiotocography, were considered as the control group. Total CK and its isoenzymes activity was measured in cord sera and 24 h after birth in peripheral blood. Abnormal FHR patterns correlate well with elevated enzyme activities. Total CK and its isoenzymes (CK-MM, CK-MB, and CK-BB) exhibited higher values in asphyxiated infants as compared to normal neonates. Electrocardiographic ischemia occurred in seven newborns who had elevated CK-MB and CK-BB levels, both at birth and within 24 h postpartum. Chromatographic study showed in normal neonates that the predominant isoenzyme was CK-MM, whereas CK-BB activity was negligible. In the newborns with abnormal FHR, CK-MB and CK-BB were increased with predominance of CK-MB. CONCLUSIONS: Antepartum fetal distress is associated with release of CK-BB, and particularly CK-MB; therefore, these biochemical markers may indicate either brain or myocardial damage.

Asphyxia Neonatorum↗

PubMed1995

The magnitude of growth hormone elevation is related with the proportion of monomeric form in acromegaly.

In acromegalic patients monomeric GH form constitutes the larger proportion of circulating GH; however, no data are available concerning the relation between total GH elevation and the predominance of GH forms. Therefore, we studied the relationship between the degree of GH elevation and the proportion of GH isoforms. Sera from 11 patients with active acromegaly were subjected to gel chromatography on Sephadex G-100 column and fractions were collected for RIA to measure GH. The monomeric form of GH was predominant and exhibited a lineal correlation (r = 0.76, p < 0.01) with the circulating GH, thus the higher elevation of GH, the major proportion of monomeric GH. IGF-1 changes correlate with changes in monomeric GH but no better than for total GH. There was a correlation observed (r = 0.65) between the proportion of low GH forms and the presence of hyperglycemia, although the physiological role of the lower molecular GH forms is still unknown. In conclusion, it was demonstrated that the relative proportion of GH molecular forms changes according to the magnitude of the elevation of total GH.

Acromegaly↗

PubMed1994

Changes in the prolactin serum isoforms secreted by a pituitary adenoma associated with therapy.

Variations in serum molecular forms of prolactin (PRL) from an adolescent woman presenting amenorrhea-galactorrhea are reported. Persistent hyperprolactinemia and hypoestrogenism were demonstrated as well as the presence of a pituitary tumor with suprasellar extension. Bromocriptine was given at progressive doses up to 37 mg daily, decreasing the hyperprolactinemia and galactorrhea. After 2 years of treatment the patient noticed symptoms of gastric intolerance, bromocriptine was discontinued and a rebound of hyperprolactinemia was observed. Lisuride was administered instead resulting in a new decrease in PRL serum levels, disappearance of galactorrhea and beginning of regular menses. Serum gel chromatographic analysis was carried out before and during lisuride treatment. The first chromatographic analysis showed a predominance of high molecular weight (approximately 66 KD) PRL, accounting for more than 90% of the immunoreactive PRL. The second chromatography showed the major peak of immunoreactive PRL displaced to the right (molecular weight of 22 KD), which was eluted near the PRL standard. With these chromatographic patterns it is concluded that the pituitary macroprolactinoma secreted different molecular forms of PRL and treatment with lisuride appeared to exert some effect on the PRL molecular size secreted by the pituitary.

Adolescent↗

PubMed1993

Distribution of growth hormone isoforms in sera from women with normal ovarian function, galactorrhea, and normoprolactinemia.

OBJECTIVE: To demonstrate if GH concentrations and molecular heterogeneity of GH correlates with the presence of galactorrhea in normoprolactinemic women with normal ovarian function. DESIGN: Aliquots of sera from women with normal ovarian function and normoprolactinemic galactorrhea were subjected to gel filtration chromatography, and the fractions were assayed for GH by the use of radioimmunoassay. Molecular weight of isoforms was calculated on a calibration curve obtained with molecular markers. The molecular variants were characterized on the basis of elution volume, molecular weight (MW), and partition coefficient. RESULTS: Basal serum GH levels were moderately elevated in all six normoprolactinemic women exhibiting galactorrhea. Chromatographic study of sera from these normoprolactinemic women showed the predominance of 40 to 50 kd molecular forms of GH as well as some very low MW GH isoforms. This pattern was different from that obtained in sera from normal women without galactorrhea who presented a predominance of heavier (> 60 kd) isoforms eluted before the GH labeled standard. The monomeric forms were present in less proportion but there was no significant difference as compared with galactorrheic group. CONCLUSIONS: Our investigation demonstrated elevated GH basal serum levels is normoprolactinemic women with galactorrhea, and chromatography in gel showed a low proportion of the large MW GH variants associated with a higher proportion of the dimeric forms and very low MW forms of GH. This is different from normal women without galactorrhea who had a predominance of heavier MW GH variants and lesser proportion of < 16 kd isoforms. It is concluded that an increased GH secretion may be responsible for abnormal lactation despite normal PRL levels in some women with normal ovarian function.

Adult↗

PubMed1993

[Determination of gastrin levels in maternal and neonatal serum as well as in amniotic fluid in acute fetal distress].

The objective was to measure gastrin (G) levels in maternal and neonatal sera as well as in amniotic fluid in patients with fetal distress and a control group. Twenty-five patients with term pregnancies were assigned to the following two groups: fifteen with acute fetal distress and ten with previous cesarean section. Maternal and neonatal blood and amniotic fluid samples were taken at the time of delivery. Differences between groups were calculated with non-parametric Mann Whitneys' U test. A significant difference (p < 0.001) between G levels in amniotic fluid of fetal distress and those of the control group was found. In conclusion, serum G levels can be used as another predictor of fetal distress, although further studies must be performed before it can be used as a clinical tool.

Acute Disease↗

PubMed1992

Antioxidant-dependent inhibition of diquat-induced toxicity in vivo.

The abilities of two experimental antioxidants (U-74006F and U-78517G), as well as the model antioxidant, diphenyl-p-phenylenediamine (DPPD), to protect against diquat-induced toxicity in male Fischer-344 rats were examined. Both experimental compounds afforded near complete protection against diquat-induced hepatotoxicity, as measured by clinical chemistry and histopathological indices. When observed, diquat-induced nephrotoxicity was also inhibited. Minimal protection was afforded by the model compound, DPPD. In follow-up studies with U-78517G, no effect on diquat-induced biliary excretion of oxidized glutathione was observed, suggesting that a shift in the thiol:disulfide ratio is not responsible for diquat-induced hepatotoxicity. These data are consistent with those from previous in vitro studies in our laboratory and are in agreement with studies by others which suggest that lipid peroxidation is an important event in diquat-induced hepatotoxicity in vivo. The antioxidant effects were largely route-independent as either oral pre-treatment alone (200 mg/kg, 24 h before diquat), intravenous pre-treatment alone (6 mg/kg, 5 min before diquat) or the combination of both treatments produced a similar degree of protection. While pre-treatment with antioxidants was quite effective, no significant U-78517G-dependent inhibition of toxicity was observed when administration was delayed by as little as 10 min post diquat. These latter data suggest that initiation of diquat-induced hepatotoxicity is rapid and that these compounds would therefore be unlikely to have clinical utility in the treatment of diquat intoxication.

Alanine Transaminase↗

PubMed1991

Variations in the molecular forms of prolactin during the menstrual cycle, pregnancy and lactation.

Size heterogeneity of immunoreactive prolactin (PRL) was studied in serum samples obtained from eight normoprolactinemic women during the menstrual cycle and five additional patients at pregnancy and lactation. Gel filtration of sera from women with normal ovarian function tested at day 10-12th of their menstrual cycle showed two predominant PRL forms, approximately 22K and 26K mol wt. In addition two polymeric variants, 50K ("big" PRL) and 100K ("big-big" PRL) were found in less proportion, accounting for approximately 34% of the total PRL immunoreactivity detected in the sera. It was also noted a low mol wt form eluting around the region of 16K mol wt. In pregnant women the major PRL form was the 22K and its proportion showed a gradual increase as progression of gestation. The polymeric PRL forms were found in substantially less amount as gestation progressed. After parturition, in nursing mothers the 22K form remained prominent and in greater concentrations than the 26K monomeric variant. Large and low mol wt PRL forms were constantly detected in sera from women during the lactation period. From these data we confirmed that PRL circulates at various molecular forms and the relative proportion of these molecular variants exhibit changes according to the physiological state. In our study the predominant form was the 22K PRL (nonglycosylated) and it was of interest to discover the presence of a low mol wt PRL which elutes in the 16K area. The significance of this latter finding is not clear at the present.

Adult↗

PubMed1990

Inhibition of carbon tetrachloride-induced lipid peroxidation by novel antioxidants in rat hepatic microsomes: dissociation from hepatoprotective effects in vivo.

The ability of two novel antioxidants, U-74,006F and U-78,517G, as well as the known antioxidant N,N'-diphenyl-p-phenylenediamine to inhibit lipid peroxidation induced by carbon tetrachloride (CCl4) was investigated in Aroclor 1254-induced rat hepatic microsomes. All three compounds completely inhibited lipid peroxidation in microsomes as measured by the formation of thiobarbituric acid reactive substances (TBARS). Inhibition of lipid peroxidation was not a function of decreased bioactivation of CCl4, as the compounds did not substantially inhibit benzphetamine N-demethylase activity or covalent binding of [14-C]CCl4 to lipid or protein. Parallel studies examined the hepatoprotective effects of the compounds in vivo. Rats were pretreated with antioxidant or vehicle prior to administration of CCl4 (300 or 600 microL/kg i.p.). Sera were collected 24 h postadministration of CCl4 and analyzed for alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities and total bilirubin. Administration of CCl4 produced elevations in ALT, moderate changes in bilirubin, and no change in ALP activities. Histological examination of CCl4-treated livers revealed lipidosis and centrilobular necrosis. The antioxidants partially improved the clinical chemistry parameters, but had minimal effects on the histological lesion. In contrast to the complete inhibition of lipid peroxidation observed in the in vitro studies, none of the antioxidants markedly protected against CCl4-induced toxicity in vivo.

Alanine Transaminase↗

PubMed1990

Adrenal cortical response in clinically normal dogs before and after adaptation to a housing environment.

58 dogs (29 males and 29 females) selected as healthy on clinical and biochemical evaluations were subjected to an ACTH adrenal function test 2 days after their admission to a veterinary hospital (t + 0). Basal female serum cortisol concentrations were significantly higher than concentrations in males (77 nmol/l versus 43 nmol/l; P less than 0.01). Concentrations post stimulation were not statistically different (P greater than 0.05) between males and females: 306 (+/- 69) nmol/l versus 291 (+/- 73) nmol/l, respectively. Twelve dogs (6 males and 6 females), randomly selected from the 58, were subjected to the same test 5 weeks later (t + 5) and 12 weeks later (t + 12). Basal cortisol concentrations were lower at t + 5 or at t + 12 than at t + 0. Post stimulation mean cortisol concentrations were lower in males than in females at t + 5 (162 versus 232 nmol/l; P less than 0.05) but not at t + 0 (262 versus 320 nmol/l; P greater than 0.05) and t + 12 (188 versus 233 nmol/l; P greater than 0.05). These findings are indicating an increased susceptibility of bitches to environmental stress.

Adaptation, Psychological↗

PubMed1989

Hepatic protection by 16, 16-dimethyl prostaglandin E2 (DMPG) against acute aflatoxin B1-induced injury in the rat.

Studies were conducted to assess the possible protective action of 16,16-dimethyl prostaglandin E2 (DMPG) against acute aflatoxin B1 (AFB1) induced hepatic injury in the rat. Evaluation of liver damage by histopathologic techniques and clinical chemistry indicated that hepatic necrosis was ameliorated by treatment with DMPG even though binding of radiolabeled (3H)-AFB1 to hepatic DNA was unaffected by this prostaglandin. However, DMPG did not protect rats against AFB1-induced mortality. These data suggest that hepatic protection by DMPG was due to mechanisms other than an interference with the activation or hepatic binding of AFB1.

16,16-Dimethylprostaglandin E2↗

PubMed1987

Renal microthrombosis following endotoxin infusion may be mediated by lipoxygenase products.

Renal microvascular thrombosis following endotoxin infusion was assessed by measuring accumulation of 125I-labeled fibrinogen and transmission electron microscopy. Endotoxin shock was induced in unanesthetized Sprague-Dawley rats using 14 mg/kg Escherichia coli endotoxin (Difco) infused intravenously over a 5-hour period. Fifteen minutes after infusion of endotoxin was started, intravenous treatment was initiated. Two-thirds of the treatment was given over a period of 20 minutes followed by the remaining dose over the next 2 hours. Five rats received methyl prednisolone sodium succinate (Solu-Medrol) (U-9,088) (39.5 mg/kg). Six rats received a Solu-Medrol analog (methyl prednisolone 21(N-Methyltaurosuberate), sodium salt) (U-67,590A) (61.08 mg/kg). Six rats received a 5-lipoxygenase inhibitor (1-naphthalenol,2,3,diethyl-4-methoxy-acetate) (U-66,855) (20 mg/kg). Six rats received a prostacyclin analog (pentanoic acid, 5- less than hexahydro-5-hydroxy-6-(3-hydroxy-1-octenyl)-3a-methyl-2(1H)- pentalenylidene greater than -calcium salt, hydrate) (U-61,431F) (0.04 mg/kg). Six rats received a thromboxane synthase inhibitor (2-benzofurancarboxylic acid, 5-(3-pyridinylmethyl), sodium salt monohydrate) (U-63,557A) (18 mg/kg). Eight endotoxin-infused rats received only normal saline. Six control rats received no endotoxin infusion, only saline. Composition and location of thrombi were assessed by transmission electron microscopy. Glomerular thrombosis was quantitated by determination of whole blood equivalents of 125I fibrin/g of tissue. Electron microscopy and radioactive quantitation demonstrated microthrombosis in the nontreated endotoxin group. The thrombi contained fibrin, platelets, erythrocytes, and leukocytes. The extent of thrombosis was significantly elevated compared to saline-treated controls. Three treated groups (U-9,088, U-67,590A, and U-66,855) all had significantly less thrombosis than the nontreated endotoxin rats. Two treated groups (U-63,557A and U-61,431F) developed glomerular thrombosis similar to untreated endotoxin rats. The results suggest that endotoxin stimulation of procoagulant activity and microthrombosis may be mediated by production of arachidonic acid metabolites via the lipoxygenase pathway.

Animals↗

PubMed1984

Timoprazole is a unique cytoprotective agent in the rat.

Timoprazole, a substituted benzimidazole, is an antisecretory agent that inhibits gastric acid secretion by interference with (H+-K+)-ATPase. In the studies reported herein, timoprazole given orally was found to be cytoprotective for the stomach when given 30 min prior to a challenge to boiling water, ethanol, or 0.6 N HCl. Timoprazole also prevented necrosis of the mucosa and acute ulcerations induced by alcohol in the rat fundus, as evaluated by histopathology. The ED50 for cytoprotection was between 1 and 3 mg/kg of timoprazole depending on the challenge, whereas the antisecretory ED50 was approximately 12 mg/kg. Timoprazole was an active antisecretory agent when given subcutaneously (ED50 10 mg/kg), but was not cytoprotective when given by this route. Indomethacin pretreatment (5 mg/kg orally) blocked the cytoprotective activity of oral timoprazole at doses of 1 or 3 mg/kg given 30 min later. However, at higher doses of timoprazole (5 mg/kg), indomethacin did not inhibit the cytoprotective activity. The ability of high doses of timoprazole to overcome the indomethacin blocks is different than the cytoprotective activity of mild irritants, which is always blocked by indomethacin. However, when tested in vitro, timoprazole exhibited only mild inhibitory activity on both prostaglandin cyclooxygenase and 15-hydroxyl-dehydrogenase and only at high doses, suggestive of nonspecific activity.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1984

Clinical and laboratory characterization of Basenjis with immunoproliferative small intestinal disease.

Eleven adult Basenji dogs with immunoproliferative small intestinal disease (IPSID) were studied. Two items of history related to the digestive tract were characteristic: (i) chronic intractable diarrhea in most dogs, and (ii) progressive emaciation. Anorexia was intermittent in only a few dogs. In addition, skin lesions of various degrees of severity were observed, including alopecia of pinnae and ventrum, hyperpigmentation and hyperkeratosis of pinnae, and necrosis and ulcerations of margins of pinnae. The cause of the skin lesions was not determined; however, hypothyroidism did not appear to contribute to the skin changes. Standard hematologic and serum chemical values were not consistently abnormal. However, a poorly regenerative anemia, mild neutrophilia, and increased aspartate aminotransferase and alanine aminotransferase activities were generally observed in severely affected dogs. The Pelger-Huet anomaly was identified in dog 3. Maldigestion and malabsorption as determined by the N-benzoyl-L-tyrosyl-p-aminobenzoic acid and d-xylose test was documented to varying degrees in dogs with IPSID. Maldigestion was correlated with functional pancreatic exocrine insufficiency. Severe malabsorption was documented in only 3 dogs. Serum gastrin values were evaluated in these dogs because of a prior observation of parietal cell hyperplasia and gastric ulceration. Hypergastrinemia was documented in 3 dogs. Additional studies will be necessary to determine whether an acid hypersecretory state contributes to the pathogenesis of IPSID in Basenjis.

4-Aminobenzoic Acid↗

PubMed1984

Immunoproliferative small intestinal disease in Basenji dogs: morphologic observations.

Eleven Basenjis with chronic diarrhea were evaluated for pathologic changes. Light microscopic and ultrastructural changes were characterized by lymphoplasmacytic infiltration of the lamina propria of the intestine and stomach and by evidence of degranulation of mast cells in close association with immunocytes. Other changes included hyperplasia of the thyroid parafollicular cells, thyroid follicular atrophy, epidermal atrophy, and ulceration of the pinna. Similarities of the condition in Basenjis and immunoproliferative small intestinal disease and Menetrier's disease in persons are presented.

Animals↗

PubMed1983

Multiple endocrine abnormalities in Basenji dogs with renal tubular dysfunction.

Three Basenji dogs with renal tubular dysfunction were studied. Hyposthenuria and diminished urine concentrating ability, indicative of nephrogenic diabetes insipidus, were documented. Metabolic acidosis, hyperchloremia, and reduction in glomerular filtration rate also were detected in all dogs. In addition, an exaggerated response to the adrenocorticotropin test and hyperaldosteronism, believed to be secondary to decreased effective circulating blood volume, were detected in all 3 dogs. Thyroxine values were decreased in all dogs and could be correlated with histopathologic changes of the thyroid gland in 2 dogs. Gastropathy and hypergastrinemia were identified in 2 dogs. Diffuse lymphocytic-plasmacytic enteritis was evident in 2 dogs. It was concluded that a urine concentrating defect that may be secondary to hypercortisolism exists in Basenji dogs with renal tubular dysfunction.

Animals↗