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Biomedical subjects

C Rodriguez

Publications and source records attributed to C Rodriguez.

At least 19 recordsLinked to original sources

Cytokine network regulating terminal maturation of human bone marrow B cells capable of spontaneous and high rate Ig secretion in vitro.

Human bone marrow (BM) B cells capable of spontaneous and high rate Ig secretion for 14 days in vitro have been described previously. We have shown recently that Ig secretion by these BM cells depends on stromal adherent BM cell-derived factors identified as IL-6 and fibronectin. Our report shows that the endogenous generation of IL-1 beta and TNF-alpha in serum-containing cultures of BM mononuclear cells (BMMC) is also involved in the control of Ig-secreting cells, because their blockade with specific antibodies markedly reduced Ig production. Further experiments revealed that IL-1 beta and TNF-alpha acted by regulating IL-6 production, as can be deduced from the following findings: 1) the inhibition of Ig secretion caused by either anti-IL-1 beta or anti-TNF-alpha antibodies could be reversed by exogenous IL-6; 2) the addition of either of these antibodies inhibited endogenous IL-6 production in BMMC cultures; 3) IL-1 beta plus TNF-alpha, but neither one alone, restored complete IL-6 and Ig production by BMMC in serum-free cultures. Moreover, adherent, but not nonadherent, BM cells were responsible for endogenous IL-1 beta and TNF-alpha secretion. Finally, IL-1 beta plus TNF-alpha induced the production of IL-6, but not of Ig, by adherent BM cells. Neither IL-6 nor Ig production was induced by adding this cytokine combination to nonadherent BM cell cultures, despite the fact that this fraction contained all the Ig-secreting cells. However, the addition of IL-6 restored Ig secretion in this cell fraction. These results suggest that IL-1 beta and TNF-alpha produced by adherent BM cells synergistically induce early IL-6 generation, which, in turn, drives BM B cell producers into the high rate Ig-secreting state.

Adult

Female Syrian hamster Harderian gland: development and effects of high environmental temperature and melatonin injections on histology and porphyrin deposits.

We have investigated the development of the Harderian glands of female Syrian hamsters from birth to 8 months of age. The effects of melatonin injections on Harderian gland histology and porphyrin deposits of female hamsters exposed to two different temperatures were also studied. The morphology of the Harderian glands from 30-day-old female hamsters resembled those of sexually mature adult animals. The intraluminal area occupied by porphyrins increased significantly between 20 to 30 days of age. However, the relative number of mast cells per mm2 rose between 30 to 90 days. Both porphyrins and mast cell numbers appeared clearly reduced in the 8-month-old group. Secretory cells characterized by large lipid droplets (type II cells) were not observed. Daily afternoon injections of 25 micrograms of melatonin to female hamsters exposed to 22 degrees C for 14 weeks resulted in the discontinuity of estrous cyclicity, a marked decrease in the intraluminal area occupied by porphyrins, a reduction of the number of mast cells per mm2, and in a marked augmentation of the number of type II cells per mm2. Although the administration of similar dosages of melatonin to hamsters exposed to an environmental temperature of 32 degrees C did not interrupt estrous cycles, a clear reduction of the area occupied by porphyrins was observed. However, the number of mast cells and type II cells per mm2 was unaffected in these animals. Our results suggest that hormones other than ovarian steroids are involved in the regulation of the female hamster Harderian glands. The possible role of melatonin on Harderian gland metabolism is discussed.

Animals

Age and food restriction alter the porphyrin concentration and mRNA levels for 5-aminolevulinate synthase in rat Harderian gland.

The effects of age and food restriction on the porphyrin concentration in Harderian glands were studied in male Fisher 344 rats. Harderian gland porphyrin concentrations increased with age; this was statistically significant in 20 month old animals compared with 3 month old animals. Food restriction (by 40%) prevented the age-associated rise in porphyrins; thus, in 20 month old food restricted rats had porphyrin concentrations similar to those found in young animals. In a second experiment, we correlated the age-associated rise in Harderian gland porphyrin concentrations with an increase in mRNA levels for 5-aminolevulinate synthase (ALV-S). Both the porphyrin concentration and ALV-S mRNA rose at 12 and 18 months of age, but decreased by 24 months of age. It is concluded that, a) porphyrin biosynthesis in the Harderian glands increases up to 20 months of age but decreases in rats that are 24 months old, and b) food restriction prevents the porphyrin rise associated with age in the Harderian gland of male Fisher 344 rats.

5-Aminolevulinate Synthetase

Behaviour modification in obese subjects with type 2 diabetes mellitus.

We have followed prospectively, 46 obese, type 2 diabetic patients for a 55-week period, in order to evaluate the efficiency of an educational programme based on behaviour modification to enhance weight loss and changes of other cardiovascular risk factors. No patient received pharmacological treatment during the study. At the end of the follow-up the patients obtained an average weight loss of 9.250 kg (range: 0.500-17.500 kg); the BMI was reduced from 34.2 +/- 0.8 kg/m2 to 30.6 +/- 1.1 kg/m2 (P less than 0.01); fasting serum glucose descended from 7.9 +/- 0.4 to 6.1 +/- 0.5 mM (P less than 0.05); SBP (systolic blood pressure) decreased from 145.7 +/- 3 to 126.4 +/- 5.1 mmHg (P less than 0.01); DBP (diastolic blood pressure) decreased from 83.5 +/- 2.5 to 65 +/- 2.6 mmHg (P less than 0.01); triglyceride levels were lowered from 164.5 +/- 12 to 109.7 +/- 10 mg/dl (P less than 0.01); HDL-cholesterol levels increased from 1.27 +/- 0.05 to 1.53 +/- 0.12 mM (P less than 0.01). Serum glucose 2 h after a 75 g glucose oral load decreased from 14.9 +/- 0.6 to 12.7 +/- 0.9 mM (P less than 0.05) on week 35 of follow-up. Twelve patients no longer presented a diabetic curve (8 normal oral glucose tolerance test (OGTT) curves, and 4 impaired glucose tolerance (IGT) curves). No significant changes in the parameters studied were obtained in the group of patients on conventional treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Behavior Therapy

The evolutionary history of Drosophila buzzatii. XXIV. Second chromosome inversions have different average effects on thorax length.

We demonstrate a genetic correlation between rearrangements of the second chromosome of D. buzzatii and thorax length, as a measure of body size. The results indicate that 2j and 2jz3 arrangements are correlated with large size, whereas 2st arrangement is correlated with small size. Some inversions (2st and 2jz3) show dominant effects and others (2j/jz3) exhibit overdominance. These results show that at least 25 per cent of body size variation may be accounted for by the studied karyotypes. The possible integration of the genotypic, phenotypic and fitness levels, and also the possible implications to life-history evolution theories, are discussed. These results suggest that, under moderate to high heritability values, some kinds of chromosomal endocyclic and/or balancing selection may be valuable mechanisms for maintenance of body size variation.

Animals

Recovery of mononuclear cell subsets after bone marrow transplantation: overabundance of CD4+CD8+ dual-positive T cells reminiscent of ontogeny.

Patients after bone marrow transplantation are immunodeficient for months to years. To understand better the pathogenesis of this immunodeficiency, we studied quantitative reconstitution of blood monocytes, natural killer (NK) cells, T cells, and B cells at 2-22 months post-transplant. The results indicate monocyte and NK counts generally recover within 2 months, followed by CD4-CD8+ T cell, B cell, and finally (after > 1 year) CD4+CD8- T cell numbers. Dual-positive CD4+CD8+ T cells (which were barely detectable in normal adults), CD4-CD8+ T cells and B cells transiently reached supranormal levels during recovery. Both CD4+CD8- and CD4-CD8+ T cells were larger than controls throughout the 2-year follow up. Comparison with neonatal and infant mononuclear cell subsets suggested the reconstitution of CD4+CD8+ T cells and B cells is similar to ontogeny. In contrast, the reconstitution of CD4+CD8- T cells did not resemble ontogeny.

B-Lymphocytes

Effects of human chorionic gonadotropin and progesterone administration on porphyrin biosynthesis and histology of the Harderian glands in male and female Syrian hamsters.

We investigated the influence of hCG and progesterone on the control of porphyrin biosynthesis and histology in the Syrian hamster Harderian glands. Castration of male hamsters caused a marked elevation in porphyrin biosynthesis as revealed by the concentrations of porphyrins and the mRNA levels of the porphyrin pathway rate-limiting enzyme, 5-aminolevulinate synthase (ALV-S). Injection of hCG into castrated male hamsters also resulted in a significant increase in both porphyrin concentrations and levels of ALV-S mRNA compared with those in saline-injected castrated hamsters. Type II cells, which are filled with large lipid vacuoles and are characteristic of male phenotype, disappeared after castration, but administration of hCG partially prevented this change. On the other hand, neither administration of hCG nor progesterone implants could increase the very high porphyrin concentrations and ALV-S mRNA levels characteristic of female Syrian hamsters. As in the case of castrated male hamsters, injections of 20 IU hCG to female Syrian hamsters increased the relative number of Type II cells per square millimeter, whereas progesterone administration did not modify the relative number of Type II cells. These results indicate that hCG can modify Harderian gland morphology in both male and female hamsters and can exert a positive control in the expression of ALV-S gene in castrated male hamsters.

5-Aminolevulinate Synthetase

Beta-adrenergic and peptide N-terminal histidine and C-terminal isoleucine stimulation of N-acetyl-transferase activity and melatonin production in the cultured rat pineal gland.

The purpose of this investigation was to compare the effect of peptide N-terminal histidine and C-terminal isoleucine (PHI) with that of the beta-adrenergic agonist isoproterenol (ISO) on N-acetyltransferase (NAT) activity and melatonin production in the cultured rat pineal gland. Pineal glands were removed and placed in organ culture containing PHI, ISO, or PHI plus ISO at different dosages, and subsequent changes in NAT activity and melatonin levels were measured. PHI stimulated these parameters in both a time- and dose-dependent manner. Combined treatment with PHI (10(-6) M) and high doses of ISO (either 10(-7) or 10(-8) M) did not potentiate the effect of the peptide in terms of either NAT activity or melatonin levels in the pineal gland. However, at a lower concentration, ISO (10(-9) M) had additive effects to those of PHI in both cultured pineals and medium. The results suggest that PHI modulates melatonin synthesis in the rat pineal gland. Furthermore, stimulation of the pineal with both PHI and ISO demonstrates an additive effect rather than a synergistic action of these compounds. It is presumed that ISO and PHI stimulate pineal melatonin production via separate receptors, but they probably use the same intracellular second messenger, cAMP, to do so. This is the first study showing an effect of the peptide PHI on pineal melatonin production in any vertebrate.

Acetyltransferases

Porphyrin metabolism in the harderian glands of Syrian hamsters: in vivo regulation by testicular hormones, lighting conditions, pineal gland, and pituitary hormones.

The porphyrin concentration in the harderian glands of male hamsters subjected to several endocrine manipulations was studied. Prolonged bilateral gonadectomy resulted in a marked increase in harderian porphyrin concentration. This change was not prevented by either pinealectomy or by constant white light exposure. Castrated hamsters exposed to constant red light showed higher porphyrin concentrations than castrated hamsters kept under white light. Among several hormones studied, serum luteinizing hormone and thyroid-stimulating hormone levels were unexpectedly higher in the constant red light exposed group than in the other groups. In order to test whether luteinizing hormone was involved in the postcastrational rise in harderian porphyrins, we administered a potent luteinizing hormone-releasing hormone (LHRH) agonist. The chronic administration of the LHRH agonist resulted in a decrease in serum luteinizing hormone (because it desensitized the LHRH receptors on the gonadotropes) and, consequently, in serum testosterone levels. However, no rise in harderian porphyrin was observed. It is concluded that the absence of testicular hormones might not be the triggering factor involved in harderian porphyrogenesis.

Animals

Effect of the infusion of p-Glu-His-Ala-OH, analog of the anorexigenic peptide, on the insulin response induced by intravenous glucose. Preliminary results with obese subjects.

The effect of the intravenous infusion of peptide p-Glu-His-Ala-OH, analog of the postulated anorexigenic peptide, on the insulinaemic response to an intravenous bolus of 20 g glucose was studied in 6 obese patients (body mass index 43.12 +/- 5.77 kg/m2). The infusion of the peptide reduced the insulinaemic response (p < 0.05) without modifying either the C-peptide or the glucose response. This decreased insulinaemic response is associated with a greater hepatic extraction of insulin (86.45 +/- 1.1% vs 82.1 +/- 1.2%; p 0.05), determined in terms of the molar ratio of the C-peptide to insulin) but not with a smaller pancreatic secretion (determined as C-peptide levels). Our results confirm that the infusion of the peptide increases the hepatic insulin extraction without its effect being mediated by any intestinal factor. Its therapeutic application remains to be determined.

Adult

Acute limited normovolemic hemodilution can be safely used in a malnourished model.

This study investigates the effects of acute limited normovolemic hemodilution (ALNH) on intestinal healing in a malnourished animal model. Twenty rabbits were randomized into three Groups: Group 1 = control; Group 2 = ALNH (removal 35% blood volume and maintenance of normovolemia with 3:1 crystalloid infusion) followed by retransfusion (RT) after small bowel anastomosis (ANA). Group 3 had a restricted diet for 3 weeks preoperatively to cause a 15 percent to 20 percent weight loss. A six cm segment of small bowel (SB) was resected and anastomosed (ANA) in all animals. Blood pressure (BP), transserosal oxygen tension (TsPao2), hematocrit (Hct), colloid oncotic pressure (COP), wet-to-dry weight ratios (WW/DW), hydroxyproline (OH-Pro) content, and tensile strength (TS) of the ANA and a segment of adjacent SB were determined. BP did not change from baseline (BL) in Group 2 during ALNH; however, it rose significantly after RT (P less than 0.05). BP decreased significantly during ALNH in Group 3 (P less than 0.05) and did not rise above baseline after RT. There was no significant change in TsPao2 from BL within groups during the experiment. The Hct and COP decreased significantly after ALNH in Groups 2 and 3 after ALNH compared to BL (P less than 0.05). After RT the Hct and COP increased and by Day 8 the Hct had risen to BL values in Group 3 but not in Group 2 (P less than 0.05), whereas COP values were not significantly different from BL in either group. There was no difference in WW/DW or TS between or among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical

Pericardiotomy improves left ventricular compliance during sepsis-induced pulmonary artery hypertension.

Sepsis-induced pulmonary artery hypertension (SIPAH) causes an increase in right ventricular (RV) afterload, dilatation of the RV, leftward shift of the interventricular septum (IVS), and therefore decreases left ventricular compliance (LVC). This study was designed to evaluate the role of pericardiotomy during SIPAH as an alternative to vasodilators (which cause a detrimental increase in shunt fraction) to improve LVC. Systemic and pulmonary hemodynamics, pulmonary function, RV, and LVC were acquired at baseline (BL), during SIPAH with closed pericardium (PAHCP) and after opening the pericardium (PAHOP). Systemic hemodynamics and pulmonary function did not change significantly during the experiment. The infusion of live bacteria induced a significant rise in mean pulmonary artery pressure from 16 +/- 5.3 at BL to 36.8 +/- 3.3 and 35.0 +/- 6.4 mm Hg during PAHCP and PAHOP, respectively, (P less than 0.05). Pulmonary vascular resistance index and right ventricular stroke work index (RVSWI) displayed a similar rise in response to SIPAH (P less than 0.05 vs BL). Pericardiotomy did not affect pulmonary hemodynamics or RVSWI. Right ventricular contractility did not increase following pulmonary hypertension while the pericardium was closed (440 +/- 78 vs 410 +/- 125, P less than 0.05); however, it rose, although not significantly, to 615 +/- 326 after pericardiotomy. RV time tension index displayed a rise during SIPAH with the pericardium intact and returned to baseline values after pericardiotomy; however, these changes were not significant. RVC did not change significantly throughout the experiment. In contrast, LVC decreased significantly after SIPAH and significantly improved after pericardiotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Lindane may enhance nocturnal pineal N-acetyltransferase activity via beta-adrenergic receptors.

Lindane, a chlorinated hydrocarbon pesticide, was previously shown to enhance the nighttime rise in pineal N-acetyltransferase (NAT) activity and melatonin as well as serum melatonin levels. The purpose of the present study was to test whether lindane acts on the pineal gland by means of a beta-adrenergic receptor mechanism. Whereas lindane (total dose 17.8 mg/kg b.wt. over 6 days) by itself significantly augmented the nocturnal levels of pineal NAT activity in otherwise untreated rats, the pesticide was ineffective in reference to this enzyme when it was given in conjunction with the beta-adrenergic receptor antagonist propranolol (20 mg/kg b.wt., one hour before lights off). The augmentation of NAT activity by lindane also caused significant reductions in pineal serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA); again, both these responses were blocked by propranolol treatment. Neither pineal 5-hydroxytryptophan nor pineal or serum melatonin levels were significantly changed as a result of either lindane or propranolol treatment. The results are consistent with the idea that lindane influences pineal 5-HT metabolism either at the level of the beta-adrenergic receptor or via the sympathetic innervation to the pineal gland.

Animals

Harderian gland porphyrin, lysosomal and type II 5'-deiodinase rhythms in Sprague-Dawley and Fischer-344 rats kept under chronic long- or short-photoperiod conditions.

1. Harderian gland porphyrin concentrations were 1.5-fold higher in Fischer-344 male rats than in Sprague-Dawley male rats and there were no differences due to exposure to LD 14:10 (LP) or LD 10:14 (SP) lighting conditions for 8 weeks in either strain. 2. 24-hr periodic regression analyses of porphyrin concentration detected a significant rhythm in both lighting conditions in both strains, with no differences in acrophase due to lighting conditions. 3. In both strains, porphyrin levels were highest in the late phase-early dark period and fell during the early part of the dark period. 4. Acid phosphatase activity did not vary with time (circadian rhythm), strain or photoperiodic lighting condition. 5. Circadian rhythms in beta-glucuronidase, alpha-mannosidase and hexosaminidase activity were present in some instances, but, probably due to the low amplitude to these rhythms, a consistent effect of strain or housing condition was not found. When 24-hr rhythms were observed in either strain, the acrophase occurred during the afternoon-early evening daylight period. 6. A significant effect of strain on mean values of type II 5'-deiodinase activity was noted in Fischer-344 rats. 7. Significant rhythms in type II 5'-deiodinase activity were found in both strains exposed to LD 10:14.

Analysis of Variance

5-aminolevulinate synthase mRNA levels in the Harderian gland of Syrian hamsters: correlation with porphyrin concentrations and regulation by androgens and melatonin.

The levels of 5-aminolevulinate synthase mRNA were investigated in the Harderian glands of male and female Syrian hamsters by using a cDNA clone from rat liver. Female hamsters showed higher levels of mRNA than those in males, while the administration of testosterone to female hamsters led to a reduction in mRNA levels. Castration of male hamsters caused a marked elevation of mRNA levels, whereas both the exposure to constant darkness or melatonin injections to castrated males partially prevented the effects of castration. Porphyrin concentration of Harderian glands showed a strong correlation with the mRNA levels of 5-aminolevulinate synthase in all the animals studied. These results lead to the conclusion that in this system, porphyrin metabolism is controlled through hormonal regulation of 5-aminolevulinate synthase gene expression.

5-Aminolevulinate Synthetase

Indole and porphyrin content of the Syrian hamster harderian glands during the proestrous and estrous phases of the estrous cycle.

Porphyrin and indole metabolism was studied in the Harderian glands of Syrian hamsters during the proestrous and estrous stages of the estrous cycle. Porphyrins remained unaltered during these stages, but levels of different indoles (5-hydroxytryptophan, 5-hydroxytryptamine, N-acetyl-5-hydroxytryptamine, and 5-hydroxyindole acetic acid) exhibited pronounced changes during the dark:light period in both proestrous and estrous. There was a strong parallelism between 5-hydroxytryptamine, N-acetyl-5-hydroxytryptamine and 5-hydroxyindole acetic acid levels. Hydroxytryptophan rhythms appeared slightly shifted from those of the other indoles. Immunoreactive melatonin present in the Harderian glands did not show a significant day-night change during the stages studied.

5-Hydroxytryptophan

Low peptic ulcer and high gastric cancer prevalence in a developing country with a high prevalence of infection by Helicobacter pylori.

We compared the prevalence rates of peptic ulcer (duodenal and gastric) and gastric cancer in 1,796 dyspeptic Peruvian patients with those reported in 2,883 similar patients from developed countries. The prevalence of total peptic ulcer was significantly lower, and that of gastric cancer significantly higher, in the Peruvian patients. The prevalence of gastric ulcer was lower but not significantly so. We deduced that the significantly lower prevalence of total peptic ulcer was directly related to the low prevalence rate of duodenal ulcer. We hypothesize that the reason for these differences was probably a higher prevalence of Helicobacter pylori-associated chronic atrophic gastritis with hypochlorhydria in the Peruvian patients. Hypochlorhydria decreases the predisposition to peptic ulcer (especially duodenal ulcer), and chronic atrophic gastritis may predispose an individual to gastric cancer.

Adult

Chronic administration of melatonin induces changes in porphyrins and in the histology of male and female hamster harderian gland: interrelation with the gonadal status.

In this paper, we have investigated the influence of melatonin on the histology and porphyrin content of the Syrian hamster Harderian glands. Daily afternoon injections of 25 micrograms of melatonin to female hamsters for 12 weeks resulted in the discontinuity of estrous cyclicity, a marked decrease in the Harderian gland intraluminal area occupied by porphyrins, and in a significant rise in the number of Type II cells. A similar decrease in porphyrins was observed after 8 weeks of ovariectomy. However, if the melatonin injections were given for only 8 weeks (without inducing gonadal atrophy), no changes were observed in the area occupied by intraluminal porphyrins, suggesting that the effects of melatonin in female Syrian hamsters might be associated with the subsequent gonadal atrophy. Castration of male hamsters induced a significant increase in porphyrins and a clear drop in the number of Type II cells. These changes were totally prevented when melatonin was administered daily from the day of castration. Our results suggest that melatonin, at least in male Syrian hamsters, plays a role in Harderian metabolism, acting directly on the Harderian secretory cells or indirectly through pituitary hormones.

Animals