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Biomedical subjects

R A Valdez

Publications and source records attributed to R A Valdez.

At least 19 recordsLinked to original sources

Metabolism of steroid hormones by Taenia solium and Taenia crassiceps cysticerci.

Previous in vitro experiments showed that both, Taenia crassiceps and Taenia solium cysticerci have the ability to metabolize exogenous androstenedione to testosterone. Here we evaluate on the capacity of both cysticerci to synthesize several sex steroid hormones, using different hormonal precursors. Experiments using thin layer chromatography (TLC) showed that both cysticerci were able to produce (3)H-hydroxyprogesterone, (3)H-androstenedione and (3)H-testosterone when (3)H-progesterone was used as the precursor. They also synthesized (3)H-androstenediol and (3)H-testosterone when (3)H-dehydroepiandrosterone was the precursor. In addition, both cysticerci interconverted (3)H-estradiol and (3)H-estrone. These results, strongly suggest the presence and activity of the Delta4 and Delta5 steroid pathway enzymes, 3beta-hydroxysteroid dehydrogenase/Delta(5-4) isomerase-like enzyme (3beta-HSD), that converts androstenediol into testosterone; and the 17beta-hydroxysteroid dehydrogenase that interconverts estradiol and estrone, in both types of cysticerci.

Androgens↗

IL-4 and IL-10 inhibition of IFN-gamma- and TNF-alpha-dependent nitric oxide production from bovine mononuclear phagocytes exposed to Babesia bovis merozoites.

The requirement for IFN-gamma and/or TNF-alpha as co-stimulants with Babesia bovis merozoites for nitric oxide (NO) production was examined, as well as the regulatory role of IL-4 and IL-10. Purified B. bovis merozoites did not induce the production of NO in undifferentiated monocytes without addition of exogenous IFN-gamma and TNF-alpha unless the monocytes taken ex vivo were producing TNF-alpha endogenously. Under the latter condition, the NO production resulting from merozoite stimulation remained IFN-gamma-dependent. There was no evidence for endogenous synthesis of TNF-alpha in monocyte-derived macrophages (MDM), and merozoites alone were incapable of inducing TNF-alpha mRNA in MDM. However, while merozoites plus IFN-gamma induced TNF-alpha mRNA expression in MDM, NO was not produced. Both IL-4 and IL-10 inhibited expression of iNOS and production of NO in merozoite-stimulated monocytes.

Animals↗

Age-related innate immune response in calves to Babesia bovis involves IL-12 induction and IL-10 modulation.

There is a strong innate immunity in calves to infection with Babesia bovis. Interleukin (IL)-12 and IL-10 have been shown in vitro to be important immunoregulatory cytokines. Here we demonstrate in vivo that the protective innate response in young calves to infection with virulent B. bovis involves the early appearance of IL-12 and interferon-gamma (IFN-gamma) transcripts in the spleen. In contrast, IL-12 and IFN-gamma mRNA expression in the spleens of adult cattle that succumbed to the infection was delayed and depressed and occurred within the context of IL-10 expression. Also in contrast with calves, there was no detectable antibody response before death in adults. A vigorous CD8+ T-cell expansion occurred in the spleens of both calves and adults.

Age Factors↗

Long-term in vivo depletion of functional CD4+ T lymphocytes from calves requires both thymectomy and anti-CD4 monoclonal antibody treatment.

In vivo depletion of lymphocyte subsets is a direct approach used for dissection of the mechanisms of protective immunity. Long-term in vivo depletion of bovine T lymphocyte subpopulations with monoclonal antibody (mAb) treatment alone has been difficult to achieve. The objective of this study was to determine whether both thymectomy and anti-CD4 mAb treatment would optimize long-term in vivo depletion of functional bovine CD4+ T lymphocytes. Calves were thymectomized and treated with high doses of anti-CD4 mAb (approximately 5 mg/kg) over 4 days followed by subsequent lower doses (approximately 0.3 mg/kg) administered twice weekly for an additional 7 weeks. Depletion of CD4+ T lymphocytes from blood, spleen and peripheral lymph nodes was significantly improved in thymectomized calves compared to thymus-intact anti-CD4 mAb-treated calves. Significant differences in percentages of CD4+ T lymphocytes between thymectomized and thymus-intact calves were sustained for the duration of the 8-week study. Depletion of CD4+ T lymphocytes from thymectomized calves resulted in complete abrogation of lymphoproliferative responses to ovalbumin. In addition, thymectomized calves treated with anti-CD4 mAb had significantly reduced immunoglobulin G1 and no detectable immunoglobulin G2 ovalbumin-specific antibody responses compared to thymus-intact anti-CD4 mAb-treated calves. The results of this study demonstrate that both thymectomy and treatment with anti-CD4 mAb are required for long-term in vivo depletion of functional bovine CD4+ T lymphocytes.

Animals↗

The age-related immunity in cattle to Babesia bovis infection involves the rapid induction of interleukin-12, interferon-gamma and inducible nitric oxide synthase mRNA expression in the spleen.

Young calves possess a strong innate immunity against Babesia bovis infection that lasts for approximately 6 months after birth and is abrogated with the removal of the spleen. This immunity is characterized as cellular involving a soluble mediator. Nitric oxide has been implicated by virtue of its babesiacidal affects in vitro, but questioned to be as effective in vivo, due to its ability to downregulate type-1 immunity. Spleen cells were obtained from 4-month-old calves and adult steers and processed for monitoring cytokine and inducible nitric oxide synthase (iNOS) mRNA expression during the response to initial B. bovis infection. The data provided evidence of a transient role for nitric oxide in innate immunity, characterized by brief iNOS induction in the spleen of calves that was not detectable in the spleens of adults. The iNOS message followed the early induction of interleukin (IL)-12 and interferon (IFN)-gamma message in calves. The induction of IL-12 and IFN-gamma message in adults was delayed until IL-10 message was induced. Transformation growth factor-beta mRNA expression levels were greater in spleen cells from adults early in infection and then declined, whereas expression levels increased in spleen cells from calves later in the infection process. Together, the data support the concept of 'first come, first serve' cytokine influence over cellular activities, the importance of a type-1 response in the control of an initial infection and the need for tight regulation in order to prevent pathology associated with over production of nitric oxide and inflammatory cytokines.

Age Factors↗

Sex steroids and parasitism: Taenia crassiceps cisticercus metabolizes exogenous androstenedione to testosterone in vitro.

Sex hormones are known to modulate immune responses and may be implicated in sex associated susceptibilities to infections. Taenia crassiceps cysticerci grow to larger numbers in female mice than in males. Gonadectomy alters the course of this infection and hormone replacement with 17beta-estradiol increases the parasite numbers. However, in chronic Taenia crassiceps cysticercosis the sex-hormone profile of males becomes more like that of the females' and progressively loose their sexual behavior. To have further insight in these outstanding endocrinological effects induced by the parasite upon the host, we investigated the parasite's capacity to produce sex steroids. In vitro experiments showed that Taenia crassiceps cysticerci transform 3H-Androstenedione to 3(H)-Testosterone, but not 3H-Pregnenolone. The production of 3H-Testosterone increased when the parasite numbers doubled. A recrystallisation procedure demonstrated that the metabolite identified by TLC was in fact testosterone. Thus, the cysticercus has the ability to use 3H-Androstenedione to make Testosterone possibly by a 17beta-Hydroxysteroid deshidrogenase-like activity in the parasite. In vivo, the parasite could use steroid precursors from the host to produce sex hormones, either accidentally or as needed for its own development, and thus alters the host's normal environment with sexual and immunological repercussions.

Androstenedione↗

An in vivo model to investigate lymphocyte-mediated immunity during acute hemoparasitic infections. Use of a monoclonal antibody to selectively deplete CD4+ T lymphocytes from thymectomized calves.

Thymectomized calves were selectively depleted of CD4+ T lymphocytes with a monoclonal antibody (mAb) specific for the bovine CD4 monomer (ILA-11). Calves were treated with high loading doses of ILA-11 during the first week of the study then treated with subsequent lower maintenance doses. Depletion of CD4+ T lymphocytes was assessed weekly by flow cytometric analysis of PBMC and mononuclear cells from lymph node and spleen biopsies. Treatment with high doses of ILA-11 resulted in rapid and marked depletion of CD4+ T lymphocytes from the peripheral blood, peripheral lymph nodes, and spleen. Although CD4+ T lymphocytes slowly returned to the peripheral blood, peripheral lymph nodes, and spleen by day 21 post-treatment, the numbers of CD4+ T lymphocytes in depleted calves remained below pre-depletion levels for the duration of the study. CD4+ T lymphocytes failed to be effectively depleted from a non-thymectomized calf treated with the mAb ILA-11. Development of a T lymphocyte depletion model in thymectomized calves will permit testing of the hypothesis that CD4+ T lymphocytes and IFN-gamma are required in cattle for control of acute anaplasmosis. In subsequent planned studies, thymectomized calves depleted of CD4+ T lymphocytes will be experimentally infected with A. marginale and parameters of disease compared between depleted and non-depleted calves.

Anaplasmosis↗

Secular increases in relative weight and adiposity among children over two decades: the Bogalusa Heart Study.

OBJECTIVE: To examine trends in relative weight and obesity among 5- to 24-year-olds between 1973 and 1994. DESIGN: A panel design consisting of seven cross-sectional surveys of schoolchildren and three surveys of post-high-school subjects. Anthropometric measurements included height, weight, and subscapular and triceps skinfolds. STUDY POPULATION: All schoolchildren residing in Ward 4 of Washington Parish, Louisiana, a biracial community, were considered eligible; participation rates were >80%. Young adults were eligible if they had participated previously as schoolchildren. A total of 26,371 examinations were performed on 11,564 persons. RESULTS: During the study period, substantial increases in mean levels of weight (0.2 kg/y) and skinfold thickness (0.15 mm/y) were observed; these changes were independent of height, age, and other covariates. The prevalence of overweight, defined by the 85th percentile of weight-for-height in 1973 to 1974, increased approximately twofold by 1994. Although secular increases were seen both among boys and girls and among blacks and whites, the largest increases were seen among 19- to 24-year-olds. Furthermore, the yearly increases in relative weight and obesity during the latter part of the study period (1983 through 1994) were approximately 50% greater than those between 1973 and 1982. CONCLUSIONS: The increasing prevalence of obesity in early life indicates a need for primary prevention. Additional study is needed to determine whether these trends are continuing to accelerate and to examine possible explanations, such as diet and physical activity, for these changes.

Adolescent↗

ECG of the month.

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Anesthetics, Inhalation↗

Migration status, socioeconomic status, and mortality rates in Mexican Americans and non-Hispanic whites: the San Antonio Heart Study.

It has been claimed that Mexican Americans have a favorable mortality experience despite their low socioeconomic status (SES). The present study compared all-cause mortality of non-Hispanic whites with that of United States-born and foreign-born (i.e., born in Mexico) Mexican Americans. Subjects were 3735 residents of San Antonio, TX, who were followed-up for 7-8 years. The sex-age adjusted death rates per 1000 person-years were higher for United States-born Mexican Americans (5.7) than for non-Hispanic whites (3.8) or for foreign-born Mexican Americans (3.6). Foreign-born Mexican Americans had the lowest socioeconomic status (SES), and non-Hispanic whites had the highest SES. After adjustment for SES, the mortality ratio for United States-born Mexican Americans compared with foreign-born Mexican Americans was 1.9 (95% confidence interval, 1.0-3.5), while the ratio for United States-born Mexican Americans compared with non-Hispanic whites was 1.0 (95% confidence interval, 0.7-1.6). Stratified analysis revealed that those in the lowest SES tertiles had threefold greater risk of death than those in the highest tertiles among both United States-born Mexican Americans and non-Hispanic whites (test for trend, P < 0.001). These data suggest that lower SES is strongly associated with increased mortality. After adjustment for SES, mortality rates were similar for United States-born Mexican Americans and non-Hispanic whites. Foreign-born Mexican Americans had the lowest mortality rates of the three groups.

Adult↗

Use of corticosteroids and aurothioglucose in a pygmy goat with pemphigus foliaceus.

Pemphigus foliaceus was diagnosed in a 20-month-old female pygmy goat. The goat had a 3-month history of chronic exfoliative dermatitis and was examined after developing alopecia and severe, asymmetric, diffuse flakes of dry, nonadherent skin scales. Pemphigus foliaceus was diagnosed on the basis of dermatohistologic findings and was confirmed by analysis of results of direct immunofluorescence testing of perilesional specimens obtained by use of a punch biopsy. The goat was successfully treated with prednisolone (immunosuppressive induction dosage; 1 mg/kg of body weight, IM, q 12 h). Remission was achieved in 1 week and was maintained by use of prednisolone (immunosuppressive maintenance dosage; 1 mg/kg, IM, q 48 h). Treatment with aurothioglucose (1 mg/kg, IM, q 7 d) that was initiated during administration of prednisolone and was continued after discontinuation of corticosteroid administration failed to prevent redevelopment of pemphigus foliaceus.

Alopecia↗

Endogenous sex hormones: impact on lipids, lipoproteins, and insulin.

Estrogen use has been reported to decrease triglyceride and low-density lipoprotein cholesterol (LDL-C) and increase high-density lipoprotein cholesterol (HDL-C). Estrogen use increases the secretion of large, very low-density lipoprotein cholesterol (VLDL-C) and also stimulates the uptake of VLDL-C by the liver and increases the catabolism of LDL-C in the liver. Sex hormones may affect several enzymes involved in the metabolism of HDL-C and triglyceride and may also affect lipolysis. In both pre- and postmenopausal women, several studies have shown that increased glucose and insulin concentrations are associated with increased free testosterone and decreased sex hormone binding globulin. The temporal direction of this relationship in premenopausal women is not clear, however. In contrast to women, increased androgen concentrations in men do not seem to be associated with increased cardiovascular risk factors, although testosterone concentrations are associated with increased HDL-C and decreased insulin concentrations. Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) appear to be associated with improved cardiovascular risk factors in men, but this connection in women is less clear.

Androgens↗

Controlled efficacy study of the bioequivalence of Strongid C and generic pyrantel tartrate in horses.

The bioequivalence of Strongid C and generic pyrantel tartrate was determined in a controlled study using 30 horses with naturally acquired endoparasitic infections. Three horses were randomly allocated to each of ten replicates based on quantitative nematode and ascarid egg counts and fecal larvae culture results. Horses within each replicate were randomly assigned to one of three treatment groups. Horses in Treatment Group 1 received only oats; horses in Treatment Group 2 received generic pyrantel tartrate pellets (2.65 mg pyrantel tartrate kg-1) mixed with oats; horses in Treatment Group 3 were fed Strongid C pellets (2.65 mg pyrantel tartrate kg-1) mixed with oats. Horses were treated daily for a 30 day continuous treatment period. At the termination of the study the horses were necropsied and endoparasites recovered, identified, and enumerated. In all instances, no significant difference (P > 0.05) in mean numbers of parasites recovered existed between horses treated with generic pyrantel tartrate and Strongid C. Numbers of gastrointestinal parasites recovered from horses treated with generic pyrantel tartrate or Strongid C were shown to be significantly different (P < 0.05) from numbers of gastrointestinal parasites recovered from non-treated controls for the large strongyles (Strongylus vulgaris, S. edentatus, and Triodontophorus spp.), small strongyles (Cyathostomum spp., Cylicocyclus spp., and Cylicostephanus spp.) and fourth-stage Parascaris equorum. Numbers of adult P. equorum recovered from horses treated with Strongid C were also significantly different (P < 0.05) from those from non-treated controls. Numbers of adult P. equorum recovered from horses treated with generic pyrantel tartrate were not significantly different (P = 0.0761) from those from non-treated controls. The determination of bioequivalence was based upon the 95% confidence interval of the difference between the mean number of parasites recovered from horses treated with generic pyrantel tartrate and the mean number of parasites recovered from horses treated with Strongid C. For all instances in which the numbers of parasites recovered from horses treated with either Strongid C or generic pyrantel tartrate were significantly different from the numbers of parasites recovered from non-treated controls, bioequivalence was demonstrated.

Animal Husbandry↗

Eosinophilic keratoconjunctivitis in a horse.

An 11-year-old Quarter Horse gelding was evaluated because of a persistent, raised band of 1- to 2-mm subepithelial plaques of the left cornea. Cytologic examination of corneal scrapings revealed numerous eosinophils and segmented neutrophils, with few mast cells, plasma cells, and lymphocytes. Bacteriologic culture yielded sparse growth of alpha-hemolytic Streptococcus and Staphylococcus spp. Histologically, the plaques consisted of subepithelial foci of fragmented and degenerated collagen fibers infiltrated by eosinophils and neutrophils, with few lymphocytes, plasma cells, and macrophages. Plaques were surrounded by a layer of brightly eosinophilic, acellular, granular material. Distribution of inflammatory cells in the conjunctiva was similar to cells in the cornea. After reepithelialization of the cornea, corticosteroid ointment was administered topically. Twenty-eight days after treatment with corticosteroids, the plaques had completely resolved. Histologic and cytologic diagnoses in this horse were similar to reports of eosinophilic keratitis in cats.

Animals↗

Decreased testosterone and dehydroepiandrosterone sulfate concentrations are associated with increased insulin and glucose concentrations in nondiabetic men.

Although many studies indicate that increased androgenicity is associated with insulin resistance and hyperinsulinemia in both premenopausal and postmenopausal women, relatively few data are available on this relationship in men. We examined the association of sex hormone-binding globulin (SHBG), total and free testosterone, dehydroepiandrosterone sulfate (DHEA-SO4), and estradiol to glucose and insulin concentrations before and during an oral glucose tolerance test in 178 men from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Total and free testosterone and DHEA-SO4 were significantly inversely associated with insulin concentrations. Free testosterone and DHEA-SO4 were also significantly inversely correlated with glucose concentrations. SHBG was weakly positively associated with glucose concentrations. Estradiol was not related to glucose or insulin concentrations. After adjustment for age, obesity, and body fat distribution, insulin concentrations remained significantly inversely correlated with free testosterone (r = -.23), total testosterone (r = -.21), and DHEA-SO4 (r = -.21; all P < .01). In conclusion, we observed that increased testosterone and DHEA-SO4 are associated with lower insulin concentrations in men. This is in striking contrast to women, where increased androgenicity is associated with insulin resistance and hyperinsulinemia.

Adult↗

Evaluation of two insulin assays in insulin resistance syndrome (syndrome X).

Recent data suggest that proinsulin is associated with cardiovascular risk factors in nondiabetic and diabetic subjects. Since most conventional insulin assays cross-react with proinsulin, it has been suggested that the associations of insulin concentrations with dyslipidemia and hypertension could actually reflect associations with proinsulin. We examined these associations by using both a conventional immunoreactive insulin assay and a specific Linco insulin assay that does not cross-react with proinsulin in 623 nondiabetic and in 180 non-insulin-dependent diabetic subjects who participated in the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Both the immunoreactive insulin assay and the specific Linco insulin assay were equally correlated with cardiovascular risk factors in nondiabetic subjects. Insulin concentrations were moderately correlated with high triglyceride and low high-density lipoprotein cholesterol levels and were weakly correlated with increased blood pressure. In diabetic subjects there were only weak associations between insulin and cardiovascular risk factors using either assay. We conclude that the association of insulin concentrations with cardiovascular risk factors is not a function of using insulin assays that cross-react with proinsulin and that for epidemiological studies of cardiovascular risk factors, conventional immunoreactive insulin assays are as good as the newer specific insulin assays.

Adult↗

Disproportionately increased proinsulin levels are associated with the insulin resistance syndrome.

Recent data suggest that proinsulin may be associated with increased cardiovascular risk factors in both diabetic and nondiabetic subjects. We examined the relation of insulin, proinsulin, and the fasting proinsulin/insulin ratio to a number of metabolic disorders believed to be related to the insulin resistance syndrome (low high density lipoprotein cholesterol and high triglyceride levels, hypertension, and impaired glucose tolerance). Proinsulin was measured by a RIA, and insulin was measured by a Linco RIA that does not cross-react with proinsulin. The increased fasting proinsulin/insulin ratio was significantly associated with hypertension, low high density lipoprotein cholesterol and high triglyceride levels, and impaired glucose tolerance in 423 nondiabetic subjects. The fasting proinsulin/insulin ratio increased significantly with the number of metabolic disorders (zero, 0.060; one, 0.086; two, 0.098; three, 0.177; four, 0.182; P < 0.001). The increased proinsulin/insulin ratio was also associated with a greater number of metabolic disorders in diabetic subjects. Our results show that particularly nondiabetic individuals with the insulin resistance syndrome not only have hyperinsulinemia as a marker of insulin resistance, but also show an increase in proinsulin relative to insulin, which may reflect relative beta-cell failure or malfunction.

Anthropometry↗

Proinsulin and specific insulin concentration in high- and low-risk populations for NIDDM.

Hyperinsulinemia and insulin resistance have been implicated as risk factors for the development of non-insulin-dependent diabetes mellitus (NIDDM). Recent data suggest that proinsulin may comprise a large proportion of immunoreactive insulin in subjects with NIDDM and possibly in those with impaired glucose tolerance (IGT) as well. Increased proinsulin concentrations are thought to be an early indicator of a failing pancreas. We examined proinsulin, insulin (using an assay that does not display appreciable cross-reactivity with proinsulin), and the fasting proinsulin:insulin ratio in 206 nondiabetic Mexican-American (a high-risk population for NIDDM) and 123 nondiabetic non-Hispanic white (a low-risk population for NIDDM) participants in the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Mexican-Americans had significantly higher fasting and 2-h proinsulin and insulin levels but similar fasting proinsulin:insulin ratios compared with non-Hispanic whites. After statistical adjustment for age, body mass index, waist-to-hip ratio, and glucose tolerance status, Mexican-Americans continued to have higher fasting and 2-h insulin and fasting and 2-h proinsulin concentrations but similar proinsulin:insulin ratios compared with non-Hispanic whites. The fasting proinsulin:insulin ratio was higher in 85 subjects with NIDDM compared with subjects with IGT or normal glucose tolerance (0.31, 0.09, and 0.07, respectively). Thus, nondiabetic subjects from a high-risk population for NIDDM are hyperinsulinemic (using an assay that does not cross-react with proinsulin) and, further, do not secrete more proinsulin relative to insulin itself than do nondiabetic subjects from a low-risk population.

Diabetes Mellitus, Type 2↗