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Biomedical subjects

R Fernández

Publications and source records attributed to R Fernández.

At least 19 recordsLinked to original sources
PubMed2000

A novel missense mutation (W797R) in the myophosphorylase gene in Spanish patients with McArdle disease.

OBJECTIVE: To investigate the degree of genetic heterogeneity of myophosphorylase deficiency (McArdle disease) in Spain through molecular studies of 10 new patients. DESIGN: The coding sequence of the entire myophosphorylase gene was sequenced in DNA extracted from muscle and blood. Restriction fragment length polymorphism analysis of polymerase chain reaction fragments was used to confirm and simplify detection of a novel mutation. SETTING: A collaborative study between 2 university laboratories in Spain and the United States. RESULTS: Five of the 10 patients harbored a novel missense mutation in exon 20, converting a tryptophan to an arginine (W797R). Three patients were homozygous for the "common" R49X mutation, and the remaining 2 patients were compound heterozygotes for R49X and a previously described missense mutation, G204S. CONCLUSIONS: The W797R missense mutation is the third novel mutation to be identified among Spanish patients. Its relative frequency suggests that it should be added to the R49X mutation in the molecular screening of McArdle disease in Spain.

Adult↗
PubMed2000

Identification of allergenic proteins in condoms by immunoenzymatic methods.

BACKGROUND: A large increase of allergy to latex proteins has been observed lately probably as a result of a great use of latex-containing goods. At present these untoward reactions have led to consideration of this problem as a health and occupational hazard. It is therefore, necessary to identify the allergens contained in latex-manufactured products and to develop effective diagnostic tools to detect sensitized individuals. OBJECTIVE: The objective of this study is to identify antigenic and allergenic components in latex condoms by using chemical, immunochemical, and immunoenzymatic methods. METHODS: The protein content of extracts obtained from several brands of condoms was determined and characterized by using a modified Lowry method, a quantitative ELISA assay and SDS-PAGE. The allergenic behavior of these proteins was studied by IgE immunoblotting, EAST and ELISA techniques, using sera from subjects allergic to latex products, particularly to latex condoms. RESULTS: Wide variations in the protein content (38 to 740 microg/g product) and composition were observed. The SDS-PAGE protein profiles showed components ranging from 7 to 94 kD of relative molecular weights; most of them were also detected in natural rubber latex. The most prominent bands were revealed in the 14 and 30 kD zones. A strong band of 69 kD in the SDS-PAGE profiles would correspond to a neoantigen, since it was not observed in natural latex. The immunoblotting analysis employing sera from 5 patients allergic to latex condoms showed the presence of 4 components with IgE binding capacity (14, 30, 69, and 94 kD). The EAST and ELISA methods showed the presence of allergens in all the condom brands studied. CONCLUSIONS: The presence of allergenic proteins in several condom brands was demonstrated by different immunoenzymatic methods.

Adolescent↗
PubMed2000

Effect of acute moderate changes in PaCO2 on global hemodynamics and gastric perfusion.

OBJECTIVE: To describe global hemodynamics and splanchnic perfusion changes in response to acute modifications in Paco2 in hemodynamically stable patients. DESIGN: Prospective, randomized crossover study. SETTING: Medical-surgical intensive care unit at a community hospital (400,000 inhabitants). PATIENTS: Ten critically ill patients who were sedated, paralyzed, and mechanically ventilated. INTERVENTIONS: Hypercapnia and hypocapnia were obtained by increasing and reducing instrumental deadspace in random order. After each intervention, patients returned to the basal condition. Each period lasted 80 min: 20 min to achieve stable Paco2 and 60 min for tonometer equilibration. In each period, global hemodynamic variables and tonometric data were collected. The periods were compared using analysis of variance. MEASUREMENTS AND MAIN RESULTS: Acute hypercapnia (Paco2 from 40+/-3 to 52+/-3 torr, p<.05) increased cardiac index (3.43+/-0.37 vs. 3.97+/-0.43 mL/min/m2, p<.05), heart rate (95+/-6 vs. 105+/-3 beats/min, p<.05), and mean pulmonary artery pressure (21+/-1 vs. 24+/-1 mm Hg, p<.05) and reduced systemic vascular resistance (992+/-98 vs. 813+/-93 dyne x sec/ cm5, p<.05) and oxygen extraction ratio (27+/-3% vs. 22+/-2%, p<.05). Standardized intramucosal Pco2 increased from 49+/-2 to 61+/-3 torr (p<.05) with an associated decrease in calculated intramucosal pH ([pHi] 7.35+/-0.03 vs. 7.25+/-0.02, p<.05), but the gastro-arterial Pco2 gradient (deltaPco2) did not change. Acute hypocapnia (Paco2 from 41+/-3 to 34+/-3 torr, p<.05; pH 7.41+/-0.01 to 7.47+/-0.02, p<.05) induced slight increments in systemic vascular resistance (995+/-117 vs. 1088 +/- 160 dyne x sec/cm5, p<.05) and oxygen extraction ratio (28+/-2% vs. 30+/-2%, p<.05). Standardized intramucosal Pco2 decreased (50+/-4 vs. 44+/-3 torr, p<.05), pHi increased (7.33+/-0.03 vs. 7.36+/-0.02; p<.05), but deltaPco2 did not change. CONCLUSIONS: In this small group of stable patients, moderate acute variations in Paco2 had a significant effect on global hemodynamics, but splanchnic perfusion, assessed by deltaPco2, did not change. In these conditions, the use of pHi to evaluate gastric perfusion appears unreliable.

Acute Disease↗
PubMed2000

[Valve replacement in severe aortic regurgitation following valve sparing operation with David's technique].

The aortic valve sparing operation is of great interest in the treatment of severe aortic insufficiency caused by annulus enlargement in aortic annuloectasia. If valve leaflets are normal, and we want to prevent complications derived from valve prosthesis and chronic anticoagulation, techniques like David s for valve preserving surgery will be performed. Although long-term results of these techniques are usually good, in some cases, like in the one we are dealing with here fibrosis is produced in the native valve, which evolves into a severe aortic insufficiency needing reoperation. We hereby describe the time related events of aortic valve deterioration, when the reintervention was indicated, and how the surgery was performed.

Adult↗
PubMed1999

Epidemiological features of rotavirus infection in Caracas, Venezuela: implications for rotavirus immunization programs.

The epidemiological features of rotavirus infection may be quite relevant for evaluation of the performance of a rotavirus vaccine in different settings, as well as for monitoring its impact during vaccination under routine conditions. This article describes some important issues regarding rotavirus epidemiology in Venezuela, where major field trials of rotavirus vaccine have been carried out. Rotaviruses was significantly more frequently observed in inpatient (43%) than in outpatient (21%) consultations for diarrhea in infants and young children. There was a high prevalence of rotavirus illness, regardless of socioeconomic conditions, but the risk of dehydration was greater among the lower socioeconomic groups. Rotavirus disease occurs year-round, with a slight seasonal pattern. Eighty-five percent of rotavirus-positive diarrheal episodes, as well as 86% of cases of dehydration due to rotavirus, occurred during the first year of life. However, rotavirus illnesses occur less commonly during the first months of life (0-2 months), which may be a result of protection by transplacental antibodies. The pattern of acquisition of rotavirus antibody was consistent with this age distribution of disease and with optimal age for vaccination. Thus, regional epidemiological characteristics of rotavirus infection may affect optimal performance of rotavirus vaccine.

Age Distribution↗
PubMed1999

Activation of the autophagy, c-FOS and ubiquitin expression, and nucleolar alterations in Schwann cells precede demyelination in tellurium-induced neuropathy.

We have used an experimental model of tellurium (Te)-induced demyelinating neuropathy in the rat to study cellular mechanisms involved in the early response of myelinating Schwann cells (SCs) to injury, prior to demyelination. Starting at postnatal day 21, weaned rats were fed a diet containing 1.1% elemental Te. The animals were killed daily within the 1st week of Te diet and the sciatic nerves were processed for the ultrastructural and immunocytochemical studies. Immunohistochemistry revealed that Te induces an increased nuclear expression of c-Fos in SCs. By electron microscopy analysis, the early cytoplasmic alteration was a dramatic disorganization of the rough endoplasmic reticulum (ER) with cisternal dilations and redistribution and loss of membrane-bound ribosomes. This was followed by a prominent activation of the macroautophagy in SCs. This process involved the formation of autophagosomes containing well-preserved cell organelles, autolysosomes with cellular remnants in various phases of degeneration and lysosomes. Te treatment also induced the expression of free ubiquitin in the perikaryal region of the SC cytoplasm. Immunogold electron microscopy showed the subcellular distribution of ubiquitin in the cytosol, around of dilated ER cisterns and in the matrix of autolysosomes and residual bodies. At the nucleolar level, fibrillarin immunofluorescence revealed nucleolar segregation in SCs exposed to Te. The ultrastructural study confirmed the segregation of the nucleolar components with a peripheral distribution of the dense fibrillar component. These results support the hypothesis that the depletion of cholesterol induced by Te treatment triggers a stress response in myelinating SCs mediated by immediate early genes of the fos family. The cellular response includes a severe disruption of the protein synthesis machinery, namely the rough ER and nucleolus, with the subsequent activation of both ubiquitin and autophagic pathways of proteins and cell organelle degradation. This cytoplasmic remodeling may represent a cytoprotective mechanism in the response of SCs to a neurotoxic stress. Furthermore, it must be a prerequisite for the induction of phenotypic changes and cell repair mechanisms in SCs.

Animals↗
PubMed1999

Improving ultrasonographic diagnosis of prostate cancer with neural networks.

To improve ultrasonographic diagnosis of prostate cancer, the authors evaluated the performance of an optimized backpropagation artificial neural network (ANN) in predicting an outcome (cancer-not cancer) from recorded information on patients admitted for transrectal ultrasonography (TRUS) performed in our Center. A total of 442 cases with complete information were selected for the study. After preselecting 17 variables (age, PSA, previous clinical diagnosis, and 14 ultrasonographic ones) through univariate analysis, a randomly selected subset of data (50%) was used to train ANNs, and the other subset (50%) was used to test the different models. The ANN achieved up to 81.82% of positive predictive value and up to 96.95% of negative predictive value vs. 67.18% and 90.97%, respectively, when compared with those obtained with logistic regression. Results and possible future practical applications are further discussed.

Biopsy↗
PubMed1999

Adult glycogenosis II with paracrystalline mitochondrial inclusions and Hirano bodies in skeletal muscle.

Hirano bodies constitute eosinophilic intracytoplasmic inclusions, typically seen in the central nervous system, where they are related to senility and certain dementias such as Alzheimer's disease or the Parkinson-dementia complex. They have been found in different tissues of experimental animals and, on rare occasions, in extraocular muscles of elderly individuals. However, to our knowledge they have not been described in skeletal muscle in locations other than extraocular muscles or associated with muscle pathology. Glycogenosis II or Pompe's disease, is a metabolic disorder caused by acid maltase deficiency and is characterized by glycogen accumulation in lysosomes in various tissues, including skeletal muscle. There are three clinical forms depending on age at onset, the most frequent being the childhood form. We present the histopathological and ultrastructural findings of a muscle biopsy performed in a case of the adult form of glycogenosis II which showed, in addition to characteristic lysosomal glycogen storage, paracrystalline mitochondrial inclusions and, as an exceptional finding, intracytoplasmic Hirano bodies in some muscle fibres.

Female↗
PubMed1999

Antifungal metabolites from the marine sponge Pachastrissa sp.: new bengamide and bengazole derivatives.

This paper reports the studies of components of an undescribed sponge in the genus Pachastrissa sp., collected along the Djibouti coast. The extract showed activity against Candida albicans. Six new bengazoles (1-6) and a new bengamide, named bengamide L (16), in addition to the known bengazoles (7-11), bengamides A (12), B (13), E (14), and F (15), and a lactone (17) are described in this paper. All structures were determined on the basis of spectroscopic studies.

Animals↗
PubMed1999

The impact of different echocardiographic diagnostic criteria on the prevalence of left ventricular hypertrophy in essential hypertension: the VITAE study. Ventriculo Izquierdo Tension Arterial España.

BACKGROUND: The prevalence of echocardiographic left ventricular hypertrophy in essential hypertension ranges from 12 to 96% depending on the threshold values used to define it, and on the selection bias. OBJECTIVE: To estimate the prevalence of echocardiographic left ventricular hypertrophy by different criteria in essential hypertensives seen in primary care centres. METHODS: Cross-sectional study in a population-based sample of 946 essential hypertensives randomly selected in 39 primary care centres across Spain. Echocardiographic studies were performed in reference hospitals by trained observers (concordance Cohen kappa index > 0.7) and analysed by a single observer. RESULTS: Prevalence of left ventricular hypertrophy ranged from 59.2% [95% confidence interval (CI) 56.1 -62.3] by Framingham criteria to 72.7% (95% CI 69.9-75.6) using the criteria of De Simone et al. (J Am Coll Cardiol 1995; 25: 1056-1062). Prevalence was higher in males by the Cornell-Penn criteria, but higher in females when using Framingham or De Simone et al. criteria. Eccentric hypertrophy was more frequent (51.3-54.1%) independently of the criteria used, particularly when adjusting wall-thickness-ratio for age (56.2-58.9%). Concentric remodelling was present in 6.5-11.4% and only 20.8-29.7% of patients had no evidence of left ventricular structural alterations. Factors independently associated with left ventricular hypertrophy in the logistic regression analysis were age, gender, systolic blood pressure, pulse pressure and body mass index. CONCLUSION: Prevalence of echo left ventricular structural alterations among essential hypertensives seen in primary care centres in Spain ranged from 70.3 to 79.2% depending on the threshold values used. Left ventricular hypertrophy ranged from 59.2 to 72.7% and age-adjusted concentric remodelling ranged from 6.5 to 11.4% depending on the criteria used. Only one-quarter of hypertensive patients were free from morphological alterations.

Aged↗
PubMed1999

Prospective comparison of therapeutical attitudes in hypertensive type 2 diabetic patients uncontrolled on monotherapy. A randomized trial: the EDICTA study.

OBJECTIVE: To compare the anti-hypertensive effect of combination therapy versus a single drug regimen schedule (dose-titration or switching to a different drug class) in type 2 diabetic hypertensive patients with inadequate blood pressure (BP) control on monotherapy. DESIGN: Prospective, randomized, open-fashion, parallel study of two therapeutic strategies during an 8-week period. SETTING: Primary care centers in Spain. PARTICIPANTS: A total of 898 men and women with type 2 diabetes mellitus and hypertension, receiving antihypertensive treatment with one single drug and whose BP was > 140 and/or 90 mmHg. INTERVENTION: Patients were randomized to a fixed combination therapy (verapamil 180 mg plus trandolapril 2 mg; Knoll AG, Ludwigshafen, Germany) or continued on a single drug regimen, either increasing the dose of the current drug or switching to a different drug class. MAIN OUTCOME MEASURE: Absolute BP reduction in the two groups of treatment, and the percentage of normalized patients (< 140/90 mmHg) in each group. RESULTS: The diastolic BP (DBP) decrease (5.6 mmHg) was significantly greater in patients treated with combination therapy, compared to patients on monotherapy (2.9 mmHg). The decrease in systolic BP (SBP) was not significantly different (11.1 versus 10.0 mmHg). In addition, a significantly higher number of patients treated with combination therapy (82% versus 74%) reached diastolic BP normalization (< 90 mmHg). CONCLUSIONS: In type 2 hypertensive patients with uncontrolled BP despite anti-hypertensive monotherapy, the change to combination therapy was more effective in attaining DBP control than any monotherapy schedule (either increasing the dose or switching to another different drug class).

Aged↗
PubMed1999

Influence of anterodorsal thalamic nuclei on the hypophyseal-adrenal axis and cardiac beta receptors in rats submitted to variable chronic stress.

The limbic structures play an important role in the control of the neuroendocrine and sympathical adrenal function in basal and stress conditions. This work was undertaken to evaluate plasma ACTH, adrenocortical activity, cardiac adrenoceptors density and affinity response to variable chronic stress (VCS) in anterodorsal thalamic nuclei (ADTN) lesioned rats. Thirty days after lesion, shamlesioned stressed animals increased plasma ACTH and corticosterone as compared to sham-lesioned unstressed animals (p < 0.05); lesioned rats increased ACTH levels after VCS (p < 0.05) as compared to unstressed-lesioned rats. Whereas in sham-lesion plasma corticosterone (C) increased after stress, in lesioned animals(C) remained unchanged as compared to unstressed-lesioned animals. In the stressed groups, adrenal C contents were below those found in unstressed rats. beta-receptors affinity, in all the experimental groups, was similar, but VCS sham-lesioned animals underwent a significant increase in cardiac D-adrenergic receptors density when compared with basal and lesioned groups (P < 0.001). Our findings would demonstrate that the increment in cardiac beta adrenoceptors density appears as a consequence of the increase in ACTH, plasma corticosterone and sympathetic response provoked by chronic stress situations. ADTN lesion attenuated this hipophisoadrenal system response to chronic stress as well as the above mentioned cardiac beta adrenoceptors density increment.

Adrenocorticotropic Hormone↗
PubMed1998

Influence of melatonin on invasive and metastatic properties of MCF-7 human breast cancer cells.

Melatonin, the principal pineal gland hormone, exerts a direct antiproliferative effect on estrogen-responsive MCF-7 cells in culture. The purpose of the current study was to investigate the effects of melatonin on the invasion capacity of MCF-7 cells. In vitro, melatonin at physiological doses (1 nM) reduced (P < 0.001) the invasiveness of tumoral cells measured in Falcon invasion chambers. Subphysiological (0.1 pM) and pharmacological concentrations (10 microM) of melatonin failed to inhibit cell invasion. Melatonin was also able to block 17beta-estradiol-induced invasion (P < 0.001). Pretreatment of MCF-7 cells with 1 nM melatonin increased the response of tumoral cells to the anti-invasive effects of this indolamine. To explore possible mechanisms by which melatonin reduces invasiveness, we measured the attachment of MCF-7 cells to a basement membrane, the chemotactic response of the cells, and their type IV collagenolytic activity. The presence of melatonin (1 nM) in the culture medium significantly reduced the ability of MCF-7 cells to attach to the basement membrane; this effect was enhanced by pretreating the cells with the same indolamine (P < 0.001). Melatonin also counteracts the stimulatory effects of 17beta-estradiol on cell adhesion (P < 0.001). The chemotactic response of MCF-7 cells also decreased in the presence of 1 nM melatonin, and this melatonin-induced reduction of cell migration was more effective on cells that were previously incubated for 5 days with melatonin than it was on nonpretreated cells (P < 0.001). The simultaneous addition of 17beta-estradiol and melatonin resulted in a significantly lower chemotactic response than that of 17beta-estradiol-treated cells (P < 0.001). However, type IV collagenolytic activity was not influenced by melatonin. Our results demonstrate that melatonin reduces the invasiveness of MCF-7 cells, causing a decrease in cell attachment and cell motility, probably by interacting with the estrogen-mediated mechanisms of MCF-7 cell invasiveness. In addition, we also studied the influence of melatonin on the expression of two cell surface adhesion molecules (E-cadherin and beta1 integrin) and an intermediate filament protein (vimentin), the expression of which has been correlated with the relative invasive capacity of human breast cancer cells. The culture of tumor cells in the presence of melatonin (1 nM) increased the membrane staining for E-cadherin and beta1 integrin as well as the number of E-cadherin and beta1 integrin immunoreactive cells (P < 0.01). Neither control MCF-7 cells nor those treated with melatonin stained for vimentin. Preliminary in vivo experiments carried out on ovariectomized athymic nude mice implanted with 17beta-estradiol pellets and inoculated with 5 x 10(6) MCF-7 cells in the inguinal mammary fat pad suggest that melatonin could decrease the tumorigenicity of these tumor cells. However, these results need further confirmation. Taken together, our results suggest that melatonin shifts MCF-7 human breast cancer cells to a lower invasive status by increasing the beta1 integrin subunit and E-cadherin expression and promoting the differentiation of tumor cells. Finally, our study points out the existence of the anti-invasive actions of melatonin as a part of the oncostatic action of melatonin.

Adipose Tissue↗
PubMed1998

H+ ATPase and Cl- interaction in regulation of MDCK cell pH.

MDCK cells display several acid-base transport systems found in intercalated cells, such as Na+-H+ exchange, H+-K+ ATPase and Cl-/HCO-3 exchange. In this work we studied the functional activity of a vacuolar H+-ATPase in MDCK cells and its chloride dependence. We measured intracellular pH (pHi) in monolayers grown on glass cover slips utilizing the pH sensitive probe BCECF. To analyze the functional activity of the H+ transporters we observed the intracellular alkalinization in response to an acute acid load due to a 20 mm NH+4 pulse, and calculated the initial rate of pHi recovery (dpHi/dt). The cells have a basal pHi of 7.17 +/- 0.01 (n = 23) and control dpHi/dt of 0.121 +/- 0.006 (n = 23) pHi units/min. This pHi recovery rate is markedly decreased when Na+ was removed, to 0.069 +/- 0.004 (n = 16). It was further reduced to 0.042 +/- 0. 005 (n = 12) when concanamycin 4.6 x 10(-8) m (a specific inhibitor of the vacuolar H+-ATPase) was added to the zero Na+ solution. When using a solution with zero Na+, low K+ (0.5 mm) plus concanamycin, pHi recovery fell again, significantly, to 0.023 +/- 0.006 (n = 14) as expected in the presence of a H+-K+-ATPase. This result was confirmed by the use of 5 x 10(-5) m Schering 28080. The Na+ independent pHi recovery was significantly reduced from 0.069 +/- 0.004 to 0.042 +/- 0.004 (n = 12) when NPPB 10(-5) m (a specific blocker of Cl- channels in renal tubules) was utilized. When the cells were preincubated in 0 Cl-/normal Na+ solution for 8 min. before the ammonium pulse, the pHi recovery fell from 0.069 +/- 0.004 to 0.041 +/- 0.007 (n = 12) in a Na+ and Cl- free solution. From these results we conclude that: (i) MDCK cells have two Na+-independent mechanisms of pHi recovery, a concanamycin sensitive H+-ATPase and a K+ dependent, Schering 28080 sensitive H+-K+ ATPase; and, (ii) pHi recovery in Na+-free medium depends on the presence of a chloride current which can be blocked by NPPB and impaired by preincubation in Cl--free medium. This finding supports a role for chloride in the function of the H+ ATPase, which might be electrical shunting or a biochemical interaction.

Animals↗
PubMed1998

Effects of verapamil on indexes of heart rate variability after acute myocardial infarction.

In patients with previous myocardial infarction (MI), depressed heart rate variability (HRV) may reflect a reduction in vagal activity and lead to cardiac electrical instability. Interventions designed to increase HRV may be of clinical interest. Data on the effects of calcium antagonists on HRV in post-MI patients are very limited. The aim of our study was to assess the effects of verapamil on HRV and on the sympathovagal balance after MI. Fifty consecutive patients with a first MI, stable sinus rhythm, and left ventricular ejection fraction >0.40 were studied. Each patient underwent two 24-hour Holter recordings, 1 at baseline and another after 4 days of treatment with verapamil retard (180 mg 2 times daily). Time and frequency domain parameters of HRV were analyzed. All time domain measurements increased significantly after verapamil: the standard deviation of all NN intervals (SDNN) from 87.1 +/- 31.4 to 98.1 +/- 30.3 ms (p <0.05) and the log-transformed percentage of pairs of adjacent NN intervals that differ >50 ms (pNN50) from 0.57 +/- 0.42 to 0.76 +/- 0.45 (p <0.01). The standard deviation of the averages of RR interevals (SDANN) (75.9 +/- 30.1 vs 86.3 +/- 29.4 ms, p <0.05), root-mean-square of successive differences between RR intervals (rMSSD) (23.0 +/- 11.7 and 28.1 +/- 13.1 ms, p <0.01), and the triangular HRV index (28.3 +/- 9.6 vs 23.4 +/- 8.6, p <0.001) also increased. A significant inverse correlation was found between improvement in HRV indexes induced by verapamil and baseline values. Spectral analysis showed a significant increase in high-frequency power of 58.5% without changes in low and very low components. With normalized units, significant reductions in low-frequency power and low- to high-frequency ratio were observed. Diabetic patients did not show any significant changes in HRV on administration of verapamil. These findings indicate that verapamil, administered during the subacute phase of MI, improves both global and short-period indexes of HRV and induces a shift in the sympathetic-parasympathetic interaction toward vagal predominance. This effect may contribute to an explanation of the beneficial effects of verapamil that have been reported in post-MI patients.

Adult↗
PubMed1998

Chronic hypervitaminosis D3 determines a decrease in C-cell numbers and calcitonin levels in rats.

Many papers have reported that chronic hypercalcemia induced either by large doses of vitamin D or by the administration of calcium or parathormone, produces hypertrophy and hyperplasia of C cells. However, more recent studies suggest that the effect of elevated calcium or 1.25(OH)2D3 concentration on the production of calcitonin may be more complex than previously suspected. To assess the validity of such a response an experimental model, where hypercalcemia was induced with vitamin D3 overdose, was designed. Male Wistar rats were administered vitamin D3 chronically (50,000 IU per 100 ml of drinking water with or without CaCl2). Serum calcium and calcitonin levels were determined. C cells were stained by immunohistochemistry using calcitonin and neuronal specific enolase (NSE) antibodies and their percentage was calculated by a morphometric analysis. We also investigated the ultrastructural characteristic of the C cells under experimental conditions. C cells did not have a proliferative response rather a decrease in their number was observed after 1 month of treatment with 25,000 IU of vitamin D3 (1.55 vs 2.43% in control animals) and 3 months with vitamin plus CaCl2 (2.27% vs 3.62% in control animals). In addition, no significant changes in serum calcitonin levels were observed during the experimental period. We conclude that rat C cells do not respond with hypertrophic and hyperplastic changes in a hypercalcemic state due to an intoxication with vitamin D3.

Animals↗