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Biomedical subjects

F Santolaria-Fernández

Publications and source records attributed to F Santolaria-Fernández.

At least 19 recordsLinked to original sources

Alcoholic myopathy: lack of effect of zinc supplementation.

A chronic form of myopathy has been described in alcoholics, characterized by atrophy of type II fibers, due both to reduced protein synthesis and increased protein breakdown. Increased production of reactive oxygen species could probably play a role in increased protein breakdown. In addition, treatment with zinc might be beneficial, since it acts as a cofactor of several enzymes involved in the synthesis of proteins and antioxidants as copper-zinc-superoxidedismutase (SOD) and selenium dependent glutathione peroxidase (GPX). Based on these facts, we analyze the relative and combined effects of ethanol, protein malnutrition and treatment with zinc, 227 mg/l in form of zinc sulphate, on muscle changes in 8 groups of adult Sprague-Dawley rats fed following the Lieber-de Carli model during 5 weeks. We also study the association between muscle histological changes and the activity of GPX, SOD and lipid peroxidation products (MDA), with hormones such as IGF-1, and with trace elements involved in antioxidant systems and/or in lipid peroxidation, such as selenium, copper, zinc, and iron. We found type IIa and IIb fiber atrophy in the alcoholic animals, especially in the low-protein fed ones. This effect was mainly due to protein deficiency. Zinc played no role at all. Muscle iron increased in ethanol, low protein fed rats, either with or without zinc, and was directly related with muscle MDA levels, which in turn were related with muscle atrophy, as was also found for serum IGF-1 levels. Ethanol was the main responsible for all these changes, although protein undernutrition also played an independent role in MDA levels. A positive interaction between ethanol and protein deficiency on serum IGF-1 was also detected. These results suggest that both protein deficiency and ethanol contribute to muscle atrophy observed in alcoholized rats; this atrophy is associated with increased lipid peroxidation and muscle iron overload. Treatment with zinc sulphate confers no benefit.

Animals↗

Effect of zinc supplementation on ethanol-mediated bone alterations.

Ethanol consumption leads to bone alterations, mainly osteoporosis. Ethanol itself may directly alter bone synthesis, but other factors, such as accompanying protein malnutrition--frequently observed in alcoholics, chronic alcoholic myopathy with muscle atrophy, alcohol induced hypogonadism or hypercortisolism, or liver damage, may all contribute to altered bone metabolism. Some data suggest that zinc may exert beneficial effects on bone growth. Based on these facts, we analyzed the relative and combined effects of ethanol, protein malnutrition and treatment with zinc, 227 mg/l in the form of zinc sulphate, on bone histology, biochemical markers of bone formation (osteocalcin) and resorption (urinary hydroxyproline excretion), and hormones involved in bone homeostasis (insulin growth factor 1 (IGF-1), vitamin D, parathormone (PTH), free testosterone and corticosterone), as well as the association between these parameters and muscle fiber area and liver fibrosis, in eight groups of adult Sprague Dawley rats fed following the Lieber de Carli model during 5 weeks. Ethanol showed an independent effect on TBV (F=14.5, p<0.001), causing it to decrease, whereas a low protein diet caused a reduction in osteoid area (F=8.9, p<0.001). Treatment with zinc increased osteoid area (F=11.2, p<0.001) and serum vitamin D levels (F=3.74, p=0.057). Both ethanol (F=45, p<0.001) and low protein diet (F=46.8, p<0.01) decreased serum osteocalcin levels. Ethanol was the only factor independently related with serum IGF-1 (F=130.24, p<0.001), and also showed a synergistic interaction with protein deficiency (p=0.027). In contrast, no change was observed in hydroxyproline excretion and serum PTH levels. No correlation was found between TBM and muscle atrophy, liver fibrosis, corticosterone, or free testosterone levels, but a significant relationship was observed between type II-b muscle fiber area and osteoid area (rho=0.34, p<0.01). Osteoporosis is, therefore, present in alcohol treated rats. Both alcohol and protein deficiency lead to reduced bone formation. Muscle atrophy is related to osteoid area, suggesting a role for chronic alcoholic myopathy in decreased bone mass. Treatment with zinc increases osteoid area, but has no effect on TBV.

Animals↗

Bone cadmium and lead in the ancient population from El Hierro, Canary Islands.

This study was performed to determine the levels of lead (Pb) and cadmium (Cd) in 63 bone samples of the prehispanic population of the island El Hierro, comparing them with the values obtained on 98 prehispanic samples from Tenerife, Fuerteventura, Gran Canaria, and La Palma, all of them in the Canary Islands, and with eight modern samples who served as controls. Prehispanic individuals from El Hierro showed the lowest bone Pb values of all the archipelago (0.72+/-1.01 mg/kg), significantly different (F=6.9, p<0.001) from the values obtained for the population of other islands such as Tenerife (4.87+/-5.36 mg/kg) or Fuerteventura (4.45+/-7.85 mg/kg) and also from those of the modern population (30.53+/-14.62 mg/kg). On the other hand, bone Cd, although slightly lower in the ancient population groups, was not significantly different when compared with the modern one. In addition, no differences were observed in bone Cd among the ancient population of the different islands. Bone lead but not cadmium kept an inverse significant relationship with the distance of the burial site both to south Spain (r=-0.31) and Atlantic Morocco (r=-0.28, p<0.001 in both cases).

Adult↗

Noninvasive estimation of bone mass in ancient vertebrae.

Histomorphometry is useful in the assessment of trabecular bone mass (TBM), and thus, in the estimation of the prevalence and intensity of osteopenia in ancient population groups. However, it is a destructive method. It is therefore necessary to explore the accuracy of nondestructive approaches, such as radiography, bone mineral density (BMD) assessed by double-energy X-ray absorptiometry (DEXA), bone density (BD), or optical density (OD) in the diagnosis of osteopenia. We selected 51 vertebrae out of a total sample composed of 333 T12, L1, and L2 vertebrae belonging to adult pre-Hispanic inhabitants from El Hierro. These vertebrae underwent histomorphometrical analysis, a fine-grained film radiography with assessment of trabecular pattern following standard methods, OD, DEXA-assessed BMD, and BD. The presence of biconcave vertebrae and wedge-shaped vertebrae was also assessed by measuring anterior height (a), posterior height (p), and height at the middle point of the vertebral body (m), and further calculating the indices 2m/(a + p) ("spine score") and a/p. Significant correlations were observed between TBM and BMD (r=0.43), TBM and BD (r=0.49), TBM and OD (r=0.52), BMD and OD (r=0.51), and BMD and BD (r=0.36), but not between TBM and the indices 2m/(a + p) and a/p. In the stepwise multiple correlation analysis between TBM and BMD, BD, and OD, OD entered into first place and BD into second place, whereas BMD became displaced; the multiple correlation coefficient was 0.63, with a standard error of 3.78. A BMD greater than 0.60 g/cm2, or a bone density greater than 0.60 g/cm3, excluded osteopenia (TBM <15%) with a specificity greater than 90%, whereas a BMD value less than 0.35 g/cm2, a BD less than 0.35 g/cm3, or optical density >1.6 excluded a normal bone mass (TBM >20%) with a specificity greater than 90%. Based on radiographic criteria on the total sample, we also conclude that the overall prevalence of vertebral fractures in the adult pre-Hispanic population of El Hierro of any age is 7.5%.

Absorptiometry, Photon↗

Bone cadmium and lead in prehistoric inhabitants and domestic animals from Gran Canaria.

Both lead and cadmium exposures derive from natural sources and also from industrialisation and certain habits, such as cigarette smoking in the case of cadmium. Some of these sources only affect human beings. The aim of this study was to determine the levels of lead and cadmium in bone samples of 16 prehispanic inhabitants of Gran Canaria, 24 prehispanic domestic animals (sheep, goat and pigs) from this island, 8 modern individuals, and 13 modern domestic animals. We found that modern individuals showed higher bone Cd values (mean=516.7+/-352.49 microg/kg, range=167.20-1125 microg/kg) than prehistoric ones (mean=85.13+/-128.96 microcg/kg, range=2.97-433 microg/kg). Values of prehistoric individuals did not differ from those of the prehistoric animals (mean=70.54+/-46.86 microg/kg, range=11.06-216.50 microg/kg), but were higher than those of the modern animals (mean=7.31+/-10.35 microg/kg, range=0-35.62 microg/kg). In the same way, modern individuals and modern animals showed approximately 7-fold higher bone Pb than ancient individuals and ancient animals, respectively. Ancient animals showed significantly lower Pb values than all the other groups, whereas modern animals showed Pb values comparable to those of the ancient individuals. A significant correlation was observed between bone Pb and Cd (r=0.61, P<0.001). Since bone cadmium accumulation leads to osteoporosis, we have also tested the relationship between histomorphometrically assessed trabecular bone mass and bone cadmium both in modern and ancient individuals. No significant relationship was found between these two parameters.

Animals↗

Protein deficiency and muscle damage in carbon tetrachloride induced liver cirrhosis.

Protein undernutrition, alterations of hormones such as IGF-1, testosterone and cortisol, and increased lipid peroxidation-which may be related with deranged metabolism of some elements such as iron (Fe), zinc (Zn), manganese (Mn), selenium (Se) or copper (Cu)-may contribute to muscle damage in non alcoholic cirrhosis. Here, we analyse the effect of protein deficiency on muscle Cu, Fe, Zn, Mn and Se in carbon-tetrachloride (CCl(4)) induced liver cirrhosis. We also study the association between protein undernutrition and these trace elements with the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and lipid peroxidation products, and how all these are related with muscle morphological changes in 40 male adult Sprague-Dawley rats. Liver cirrhosis was induced by intraperitoneal injection of CCl(4) to 10 rats fed a 2% protein diet, and to another 10 fed a 18% protein control diet. Two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. After sacrifice (6 weeks later), we found type IIa fibre atrophy in the cirrhotic animals, especially in the low-protein fed ones and this was due to protein deficiency. Muscle Fe increased in low protein fed cirrhotic rats. No relationship was found between muscle changes and any of the hormones, enzymes and trace elements analysed, or with liver fibrosis. These results suggest that muscle atrophy observed in CCl(4)-induced cirrhosis is related with protein deficiency, but not with cirrhosis itself.

Adenosine Triphosphatases↗

Case report. Pulmonary involvement in an adult male affected by type B Niemann-Pick disease.

We report the case of a 39-year-old male patient affected by type B Niemann-Pick disease, in whom pulmonary involvement became evident 15 years after the initial diagnosis. Pulmonary involvement was discovered incidentally during the evaluation of a dry cough and exertional dyspnoea which occurred in the context of an acute febrile, self-limiting illness. In this case, the pulmonary involvement is clinically mild, with minimal alteration of the diffusing capacity for carbon monoxide (DL(CO)), despite moderate fibrosis and widespread infiltration of both alveoli and interstitium by sea blue histiocytes.

Adult↗

Effects of protein deficiency on liver trace elements and antioxidant activity in carbon tetrachloride-induced liver cirrhosis.

In liver cirrhosis, liver tissue becomes progressively substituted by fibrosis, ultimately leading to architectural distortion, liver circulatory changes, and liver failure. Some data support the hypothesis that protein undernutrition may play a role in the development and progression of nonalcoholic liver cirrhosis and that this progression is at least partially mediated by changes in glutathione peroxidase (GPX), superoxide dismutase (SOD), and other antioxidative systems, leading to an increase in lipid peroxidation. We analyzed the effects of protein deficiency on liver Cu, Fe, Zn, Mn, and Se in carbon tetrachloride (CCl4)-induced liver cirrhosis, the relation of protein undernutrition and these trace elements with the activity of some hepatic antioxidative enzymatic mechanisms, and the relation of all of them with morphological and biochemical changes in 40 male adult Sprague-Dawley rats divided in four groups. Liver cirrhosis was induced by intraperitoneal injection of CCl4 to 10 rats fed a 2% protein diet and another 10 fed a 18% protein control diet; two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. The study period lasted 6 wk. GPX, SOD, and lipid peroxidation products as well as Zn, Cu, Mn, Se, and Fe were determined in liver samples. We found that liver GPX and Se were reduced in the cirrhotic animals, especially in the low-protein-fed ones, protein deficiency, but not cirrhosis, exerting the main effects. A close correlation was found between liver GPX and serum albumin and weight loss and an inverse one among GPX and hepatocyte ballooning, liver fibrosis, and fat, histomorphometrically determined. These results suggest a pathogenetic role of decreased GPX in the progression of liver disease, which may become enhanced by concomitant protein undernutrition. In addition to iron, the levels of which were increased in the malnourished rats, no differences were found regarding the other trace elements, SOD activity, and lipid peroxidation products.

Animals↗

Double-energy X-ray absorptiometry in the diagnosis of osteopenia in ancient skeletal remains.

Bone mineral density (BMD) assessed by double-energy X-ray absorptiometry (DEXA) accurately estimates the bone mass in living individuals, and is thus the method usually employed in the diagnosis and follow-up of osteopenia. It is preferred, in clinical settings, to the more invasive and destructive histomorphometrical assessment of trabecular bone mass in undecalcified bone samples. This study was performed in order to examine the value of DEXA-assessed BMD at the proximal end of the right tibia, either alone or in combination with the cortico-medullary index at the midshaft point of the right tibia (CMI), in the diagnosis of osteopenia in a prehistoric sample composed of 95 pre-Hispanic individuals from Gran Canaria. Age at death could be estimated in 34 cases. Diagnosis of osteopenia was performed by histomorphometrical assessment of trabecular bone mass (TBM) in an undecalcified bone section of a small portion of the proximal epiphysis of the right tibia. A high prevalence of osteopenia was found among the population of Gran Canaria. Both TBM and BMD were significantly lower in the older individuals than in younger ones, and BMD was also significantly lower in female individuals. BMD was moderately correlated with TBM (r = +0.51); the correlation was higher if CMI was included (multiple r = +0.615). BMD values lower than 0.7 g/cm2 showed a high specificity (>93%) at excluding normal TBM values. These methods were prospectively applied in a further sample of 21 right tibiae from Gran Canaria, Tenerife, and El Hierro. The results were similar to those obtained in the larger sample. Thus, DEXA-assessed BMD combined with CMI (noninvasive procedures) may be useful in detecting osteopenia in ancient populations.

Absorptiometry, Photon↗

Hair zinc and copper in chronic alcoholics.

Chronic alcoholics frequently show associated malnutrition. Both ethanol and malnutrition exert profound changes on zinc and copper metabolism. In this study, we found higher hair zinc and copper values in 43 male alcoholics than in 39 controls. Hair copper was significantly related to the amount of ethanol consumed, whereas hair zinc was higher in consumers of distilled beverages. No relation was observed between hair zinc and copper and nutritional status, kind of diet consumed, style of life, and liver cirrhosis. Consequently, hair zinc and copper levels are related only with alcohol intake.

Adult↗

Paleonutritional analysis of the pre-Hispanic population from Fuerteventura (Canary Islands).

In this study, from histological and chemical perspectives, we analyse the human remains belonging to the pre-Hispanic inhabitants from Fuerteventura (one of the Canary Islands) and compare the results with those obtained on a sample of pre-Hispanic inhabitants from Gran Canaria (Canary Islands). We observe that trabecular bone mass was normal in the samples from Fuerteventura except for an elderly woman; this result is in sharp contrast with the decreased bone mass observed in the population from Gran Canaria. The pre-Hispanic population from Fuerteventura showed lower bone strontium, Sr/Ca ratio, and bone barium, but slightly higher bone copper, than that from Gran Canaria. All these data indicate a greater consumption of marine products by the population of Fuerteventura. The high prevalence of osteoporosis observed in the population from Gran Canaria may be interpreted as a consequence of protein-calorie malnutrition, a condition which seemed to be not so prevalent in the population of Fuerteventura.

Africa↗

Auricular exostoses among the prehistoric population of different islands of the Canary archipelago.

It is generally believed that auricular exostoses are due to prolonged exposure to cold water, so their existence in ancient remains may inform us about economic activities in the past. This study was performed to analyze the prevalence of auricular exostoses among 150 pre-Hispanic individuals of different islands of the Canary archipelago. Individuals from Gran Canaria (6/26), Fuerteventura (1/15), and Tenerife (2/64), but not from El Hierro (0/45), showed auricular exostoses, thus supporting the hypothesis of a greater reliance on fishing and shellfishing in the former 3 islands.

Adult↗

Sex determination by discriminant function analysis of the right tibia in the prehispanic population of the Canary Islands.

This study has been performed in order to define standards usable to determine the sex of prehispanic individuals from the Canary Islands from their skeletal remains. Osteometric information at the right tibia was obtained from 59 complete skeletons from Gran Canaria, housed in the Museo Canario (Las Palmas), 45 males and 14 females (this constitutes the totality of complete prehispanic skeletons known from Gran Canaria). The parameters measured were: tibial length, proximal and distal epiphyseal breadth, transverse and anteroposterior diameter, perimeter at the nutrition foramen levels and minimum shaft perimeter. These parameters were subjected to different SPSS discriminant function analysis, combining all of them, or only the proximal or distal ones, without tibial length, etc., in order to obtain functions usable even if only bone fragments are available. Transverse diameter, proximal epiphyseal breadth and minimum shaft perimeter showed the highest discriminant power. The functions obtained showed high average accuracies, ranging from 94.9 to 98.3%, with female accuracies of 100%. The functions obtained were further applied to a test prehispanic population (ten males and ten females) from El Hierro. Overall accuracies of the functions when applied to this population ranged from 65 to 94.7%, with female accuracies ranging 80% to 100%.

Atlantic Islands↗

Lack of relationship between plasma thrombomodulin and portal hypertension in alcoholic liver disease.

The present study was performed to analyze the relationship between portal hypertension and alterations of the endothelium-derived proteins thrombomodulin, plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1), which were determined in plasma samples of 28 alcoholic cirrhotic patients and 46 controls. Although cirrhotics showed lower levels of PAI-1, but higher thrombomodulin and t-PA levels than controls, no relationship was observed between thrombomodulin, t-PA or PAI-1 and portal pressure. Therefore, the hypothesis that splachnic endothelial damage secondary to portal hypertension leads to altered thrombomodulin, t-PA and PAI-1 levels in alcoholic cirrhosis is not supported by the results of this study.

Adult↗

Bone histology of prehistoric inhabitants of the Canary Islands: comparison between El Hierro and Gran Canaria.

The trabecular bone mass (TBM) of the proximal epiphyses of right tibiae belonging to 273 prehispanic inhabitants of Gran Canaria (60. 81% males and 35.53% females) were assessed by histomorphometrical analysis of undecalcified samples and compared with that of 41 samples from El Hierro (52.63% males and 47.37% females). Among the prehispanic population of Gran Canaria 19.05% showed TBM values below 13.5% and 30.40% below 15%, although individual variability was high (range 6.71-35.4%). In sharp contrast with these results, only one case (2.44%) from El Hierro showed a TBM value below 15%, whereas mean TBM (23.50;+/- 5.60%) was significantly higher than that of the population of Gran Canaria (17.88 +/- 5.20%). The high prevalence of osteoporosis on Gran Canaria may reflect protein-calorie malnutrition. Prehistorically Gran Canaria exhibited a relatively high population density (30-40/km(2)) and a strong reliance on agriculture, in contrast with a lower population density (4/km(2)) on the island El Hierro, where the population consumed mainly marine products.

Adolescent↗

Coagulation inhibitors in alcoholic liver cirrhosis.

In the present study we have analyzed the relationship between coagulation inhibitors (antithrombin III, protein C and S, thrombomodulin), liver function impairment, and plasma activity of the endothelium-derived proteins plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) in 27 alcoholic cirrhotic patients and 25 controls. Cirrhotics showed decreased values of all the mentioned parameters except for thrombomodulin, PAI-1, and t-PA. Thrombomodulin and t-PA levels were higher in cirrhotics. No relationship was observed between thrombomodulin and t-PA or PAI-1. Protein C and antithrombin III levels were significantly lower in Child's C patients, whereas no correlation was found between t-PA and thrombomodulin and hepatic function derangement. PAI-1 activity was normal in our patients.

Adult↗

Relative and combined effects of propylthiouracil, ethanol and protein deficiency on muscle.

A hypermetabolic state with increased oxygen consumption has been described in alcoholic hepatitis, playing a major role in ethanol-induced liver damage. Based on its ability to decrease oxygen consumption, propylthiouracil (PTU) has been proposed as a therapeutic agent in this context. On the other hand, several muscle changes have been described in hypothyroidism, including both atrophy and hypertrophy of muscle fibres. The aim of this experimental study was to analyse the effects of PTU on the alcohol-induced changes in muscle fibre size and proportion, also taking into account the presence or absence of protein deficiency. The study was performed on 64 male Wistar rats divided into eight groups, fed with: (1) Lieber-DeCarli control diet: (2) an isocaloric 36% ethanol-containing diet: (3) an isocaloric 2% protein-containing diet: (4) an isocaloric 36% ethanol 2% protein-containing diet, without and with PTU, respectively. Right gastrocnemius muscle was removed 2 months later and histochemical and morphometric studies were performed. Type IIb fibre atrophy was observed both in the alcoholic and protein-deficient animals, but not in the PTU-treated animals. The combination of protein deficiency and ethanol led to a more marked type IIb atrophy, with PTU reversing this effect. Malnutrition led to a decrease in type I fibre diameter: ethanol and PTU caused an increase in its size and PTU reversed the effect of protein deficiency. Proportion of type IIb fibres decreased in the three experimental groups without PTU with respect to the control, especially in the alcoholic protein-deficient animals. PTU-treated animals, especially those fed a low-protein diet, showed a more marked reduction in type IIb fibre proportion than that presented by the groups without PTU. However, an increase in type I fibre proportion was observed in the PTU-treated animals, especially marked in those fed a low-protein diet. Thus, PTU seems to ameliorate ethanol-induced changes on type IIb muscle fibres.

Animals↗