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Biomedical subjects

N Hernández

Publications and source records attributed to N Hernández.

At least 19 recordsLinked to original sources

[Changes in exercise tolerance, health related quality of life, and peripheral muscle characteristics of chronic obstructive pulmonary disease patients after 6 weeks' training].

OBJECTIVE: This study was designed to assess changes in skeletal muscle characteristics after 6 weeks' high-intensity physical training of patients with moderate to severe chronic obstructive pulmonary disease (COPD) and to determine how the changes were related to improvements in exercise tolerance and health related quality of life (HRQL). PATIENTS AND METHODS: Ten patients with a mean (SD) age of 60 (10) years and a forced expiratory volume in 1 second of 32% (9%) were enrolled. The effect of training on the 6-minute walk test, HRQL questionnaires, and skeletal muscles was examined for the 8 patients who completed the program. The structural and chemical characteristics of skeletal muscles before and after training were studied in vastus lateralis muscle biopsies. RESULTS: Training significantly modified the 6-minute walk test (P<.01), HRQL (P<.05), and citrate synthetase activity (P<.05). Changes in distances walked during the 6-minute walk test were significantly related to changes in the mean area of fibers (r=0.81). CONCLUSIONS: The results of this study indicate that 6 weeks of high-intensity physical training of COPD patients produces moderate changes in skeletal muscles which could partly explain improvements observed in exercise tolerance after respiratory rehabilitation.

Aged↗

Genotoxic and cytotoxic studies of beta-sitosterol and pteropodine in mouse.

Beta-sitosterol (BS) and pteropodine (PT) are constituents of various plants with pharmacological activities potentially useful to man. The chemicals themselves possess biomedical properties related to the modulation of the immune and the nervous systems, as well as to the inflammatory process. Therefore, safety evaluation of the compounds is necessary in regard to their probable beneficial use in human health. The present study evaluates their genotoxic and cytotoxic potential by determining the capacity of the compounds to induce sister chromatid exchanges (SCE), or to alter cellular proliferation kinetics (CPK) and the mitotic index (MI) in mouse bone marrow cells. Besides, it also determines their capacity to increase the rate of micronucleated polychromatic erythrocytes (MNPE) in peripheral mouse blood, and the relationship polychromatic erythrocytes/normochromatic erythrocytes (PE/NE) as an index of cytotoxicity. For the first assay, four doses of each compound were tested: 200, 400, 600, and 1000 mg/kg in case of BS, and 100, 200, 300, and 600 mg/kg for PT. The results in regard to both agents showed no SCE increase induced by any of the tested doses, as well as no alteration in the CPK, or in the MI. With respect to the second assay, the results obtained with the two agents were also negative for both the MNPE and the PE/NE index along the daily evaluation made for four days. In the present study, the highest tested dose corresponded to 80% of the LD(50) obtained for BS and to 78% in the case of PT. The results obtained establish that the studied agents have neither genotoxic nor cytotoxic effect on the model used, and therefore they encourage studies on their pharmacological properties.

Journal Article↗

Skeletal muscle inflammation and nitric oxide in patients with COPD.

In chronic obstructive pulmonary disease (COPD) the presence of systemic inflammation has been associated with peripheral muscle abnormalities and weight loss. To study whether inflammatory factors are important in these processes, the present study compared the skeletal muscle levels of nitrite, nitrate, nitrotyrosine, neuronal, endothelial and inducible nitric oxide synthases (nNOS, eNOS, and iNOS, respectively), and inflammatory markers (tumour necrosis factor (TNF)-alpha, CD154 and CD163) in 15 patients (forced expiratory volume in one second 43+/-11%) and 14 controls. All these markers were also compared between patients with normal and low body weight. Nitrite (12.5+/-2.6 versus 17.0+/-3.4 micromol.mg(-1) protein), nitrate (20.7+/-2.4 versus 24.4+/-4.5 micromol.mg(-1) protein) and eNOS (31.9+/-4.6 versus 43.6+/-7.5 ng.mg(-1) protein) were lower in COPD patients than in controls. Nitrotyrosine (25.6+/-5.4 versus 6.6+/-3.3 ng.mg(-1) protein), iNOS expression (32+/-9.5 versus 7.16+/-2.7 ng.mg(-1) protein), TNF-alpha (257+/-160 versus 48.3+/-4.4 pg.mg(-1) protein) and CD163 (6.4+/-2.1 versus 0.8+/-0.4 ng.mg(-1) protein) were higher in COPD patients than in controls. CD154 levels were 15.7+/-7.0 ng.mg(-1) protein in COPD patients and undetectable in controls. Similar levels of all these markers were observed in COPD patients with normal and low body weight. In conclusion, these findings suggest the presence of an inflammatory process in the muscle tissue of chronic obstructive pulmonary disease patients, and argue in favour of its participation in the pathogenesis of skeletal muscle abnormalities.

Aged↗

Glutathione and glutamate levels in the diaphragm of patients with chronic obstructive pulmonary disease.

Recently, decreased glutamate (Glu) and reduced glutathione (GSH) levels were reported in the quadriceps femoris of patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate whether Glu and GSH levels are also modified in the diaphragm of these patients. Nine male COPD patients (forced expiratory volume in one second (FEV1) range 28-68% of the predicted value) and seven male patients with normal pulmonary function (mean +/- SD FEV1 86 +/- 3% pred) submitted to thoracotomy were included. Biopsy specimens were taken from the diaphragm (both groups) and the quadriceps femoris (COPD group alone) in order to assess fibre size, myosin heavy chain expression, GSH levels and amino acid profile. The COPD group was characterised by preserved fibre size, a higher proportion of type I fibres (mean +/- SEM 70 +/- 3 versus 26 +/- 4%), and higher Glu and GSH content in the diaphragm compared to the quadriceps muscle. However, Glu and GSH levels were similar in diaphragm from the COPD and control groups. Glu level correlated with GSH level in both muscles. No significant correlation was found between Glu or GSH level and fibre size or proportions. This study shows that glutamate and reduced glutathione levels are preserved in the diaphragm of chronic obstructive pulmonary disease patients. Alterations in glutamate and reduced glutathione metabolism are muscle-specific in chronic obstructive pulmonary disease, affecting the quadriceps femoris but not the diaphragm. Glutamate and reduced glutathione levels are strongly interrelated in both muscles, independent of fibre type distribution and fibre size.

Aged↗

Inflammation and nitric oxide production in skeletal muscle of type 2 diabetic patients.

An inflammatory process may be involved in nitric oxide production in skeletal muscle of type 2 diabetic patients. Nitric oxide generation in skeletal muscle was assessed in 14 non-complicated type 2 diabetic patients and in 12 healthy subjects. In samples of quadriceps femoris muscle, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), nitrite, nitrate and nitrotyrosine were determined. The macrophage-specific antigen CD163, the T-cell membrane factor CD154 and tumour necrosis factor-alpha (TNF-alpha) were also assayed. In six patients, ultrastructural analysis of muscle was performed. Nitrites and nitrates were increased in patients as compared to controls (22.7+/-4.5 and 32.7+/-7.0 vs 16.0+/-2.9 and 22.8+/-4.0 micromol/mg protein; P<0.001, Mann-Whitney U test). Endothelial NOS was similar in diabetic and control subjects (36.4+/-13.8 vs 36.3+/-6.8 ng/mg protein), contrasting with the significant increase of iNOS recorded in patients (34.3+/-13.0 vs 8.5+/-2.8 ng/mg protein, P<0.00002). Nitrotyrosine levels were higher in the patient than in the control group (42.1+/-24.4 vs 10.3+/-2.5 ng/mg protein, P<0.00002), as were CD163 (10-fold) and TNF-alpha (fourfold) levels. Furthermore, CD154 levels were detectable only in the patient samples (10.2+/-5.3 ng/mg protein). By multiple-regression analysis, changes in glycated haemoglobin values could predict 96% variation in nitrotyrosine. Macrophages were present in all muscle samples analysed by electromicroscopy. The increased levels of CD163, CD154 and TNF-alpha indicate that an inflammatory process occurs in skeletal muscle of type 2 diabetic patients. This may contribute to iNOS induction, muscle damage and insulin resistance.

Adult↗

Development and validation of an enzyme-linked immunosorbent assay (ELISA) for recombinant human gamma interferon.

A one-site ELISA for the quantification of recombinant human gamma interferon (rh-IFN-gamma) was developed and validated. A single monoclonal antibody (Mab) was used as a "catching" antibody and as a horseradish peroxidase (HRP)-labeled conjugate. Detection limit and quantification limit of this assay were estimated to be 1.26 and 15 ng/mL, respectively, and the coefficient of variation was below 15%. The ELISA was specific for rh-IFN-gamma, showing no cross reactivity to other related molecules in the range of the concentrations studied. The results correlated well with those obtained by a bioassay method. By using this assay, it was demonstrated that 0.01-1% (v/v) Tween 80 protected rh-IFN-gamma during freezing and thawing.

Antibodies, Monoclonal↗

[Basic structure of respiratory and peripheral muscles in the beagle dog].

BACKGROUND: The dog is one of the most widely used animals in studies of respiratory physiopathology, mainly because of its physiological characteristics. However, ethical and legal constraints are placed on the use of some species in our context. OBJECTIVE: We studied the underlying structural features of respiratory and peripheral muscles in the beagle dog in order to suggest reference values for future studies. METHOD: Fourteen young beagles were selected. Samples were taken from the costal diaphragm (DFG), external intercostal (EI) and vastus medialis (VM) muscles. We analyzed fiber percentages and sizes (immunohistochemistry, using myosin heavy chain [MyHC (monoclonal antibodies), percentages and absolute number of MyHC isoforms (electrophoresis and ELISA), and level of membrane damage (immunohistochemistry, using anti-fibronectin monoclonal antibodies). RESULTS: In the EI muscle, type I fibers were larger (by 20%) than type II fibers. Fibers resistant to fatigue (type I) predominated greatly over fast contraction fibers (type II) in all three muscles analyzed (DFG 57% 11% vs. 45% 12%; EI 58% 5% vs. 43% 5%; and VM 70% 8% vs. 34% 7 %). Few hybrid fibers (co-expression of fast and slow MyHC) were found and their percentages were similar in all three muscles. The absolute expression of MyHC was greater in the VM than in the respiratory muscles, with a relative predominance of the MyHC I isoform in the DFG and VM muscles and a similar tendency in the EI muscle. Membrane damage was very slight in all three muscles. CONCLUSIONS: The phenotype characteristics of respiratory and peripheral muscles in the beagle correspond to what we would expect functionally for a breed initially selected for hunting, with minimal lesions under normal circumstances, a predominance of fibers and proteins that are resistant to fatigue, and larger fibers in the EI, a muscle that plays a role in respiration in dogs.

Animals↗

Antinociception induced by PAG-microinjected dipyrone (metamizol) in rats: involvement of spinal endogenous opioids.

Dipyrone microinjection into the periaqueductal gray matter (PAG) elicits antinociception in rats by activating endogenous opioidergic circuits in PAG and the rostral ventromedial medulla. We have now found that endogenous opioids in the spinal cord are also involved. Responses of dorsal spinal neurons to noxious stimulation of a hindpaw were diminished (to 38-44%) by dipyrone microinjection (100 microg/0.5 microl) into the PAG. This was abolished by application of naloxone (50 microg/50 microl) to the spinal cord. The fact that dipyrone, a non-opioid analgesic, activates opioidergic circuits may be clinically important.

Afferent Pathways↗

Muscle fiber composition and capillarization in relation to metabolic alterations in hypertensive men.

The aim of this study was to determine if there is a relationship among skeletal muscle fiber composition, capillarization, blood pressure (BP) and/or the components of the metabolic syndrome. Two groups were compared: 8 recently diagnosed, untreated, hypertensive men (BP > or = 140/90) and 7 normotensive men as controls. Muscle biopsies were taken from the vastus lateralis part of quadriceps femoris muscle in order to assess: fiber type proportion, capillarization, hexokinase, citrate synthase, beta-hydroxyacyl CoA dehydrogenase activities; lipoprotein lipase mass and activity, free fatty acids and triglycerides. Serum levels of insulin, glucose, cholesterol, uric acid and triglycerides were also assayed. Hypertensive patients had higher insulin levels and insulin resistance [homeostasis model assessment (HOMA)], a decreased hexokinase activity and an increase of muscle lipoprotein lipase mass as compared to controls. Interestingly, correlations among values differ in each group. The percentage of type IIB fibers was related to diastolic BP (blood pressure) in control and to mean BP in hypertensive subjects. Serum cholesterol and glucose were inversely related to the percentage of type I fibers in the control subjects. Negative correlations between capillarization and glucose, cholesterol and uric acid levels were found in control subjects. In all subjects, a strong correlation was found between SBP (systolic BP) and DBP (diastolic BP), and insulin resistance (IR) and uric acid levels. Muscle fiber type proportion and capillarization were related to blood pressure and components of the metabolic syndrome.

Adult↗

Metabolic changes in DOCA-salt hypertensive rats.

In a previous report, we observed an altered proportion of fiber types and a reduction of capillary per fiber ratio in extensor digitorus longus (EDL) and soleus (SOL) muscles of deoxicorticosterone acetate (DOCA)-salt hypertensive rats when compared with controls. The aim of the present study was to ascertain various carbohydrate and lipid enzyme activities and substrates that may be involved in the morphological changes reported. In the SOL muscle of hypertensive rats, glucose, glycogen and triglycerides (TG) levels were increased, citrate synthase (CS) and beta-hydroxy-acyl-CoA dehydrogenase (HAD) activities were reduced, while hexokinase (HK) and lipoprotein lipase (LPL), LPL mass, lactate and free fatty acids (FFA) levels were unchanged. In EDL muscles of hypertensive rats, glycogen levels and LPL mass were higher than in controls, while CS, HAD, HK, and LPL activities and glucose, lactate, FFA and TG levels were unmodified. Serum levels of insulin, TG, cholesterol and FFA were increased while glucose levels were decreased and high-density lipoprotein-cholesterol levels were similar in hypertensive rats when compared with controls. In conclusion, hypertensive rats showed increased glycogen in both EDL and SOL muscles, with hyperinsulinemia and reduced glycemia. Hyperinsulinemia might have been a compensatory response to insulin resistance. The oxidative capacity of SOL muscle was reduced indicating that glucose uptake was conduced via non-oxidative metabolism. TG, FFA and cholesterol were increased in serum and TG in SOL muscle.

3-Hydroxyacyl CoA Dehydrogenases↗

Capillary changes in skeletal muscle of patients with essential hypertension.

Arterial hypertension produces changes along the vascular tree. However, there are few reports on its effect on human muscle capillaries. This study demonstrates the effects of essential hypertension on the capillaries of human quadriceps muscle. Muscle biopsy was taken from quadriceps femoris in eight men with recent diagnosis of essential hypertension, without treatment. Biopsies were also taken from eight normotensive men and were used as controls. Fiber types were classified by ATPase reaction, capillaries counted in alpha-amylase-PAS stained sections and ultrastructure studied by conventional methods of transmission electron microscopy. No changes were found in capillaries or muscle fiber types by histochemical methods. However, electron microscopy revealed abnormal capillaries with endothelial cells infoldings into the lumen, as well as occluded or degenerated capillaries. In some cases the endothelial cell area covered by pericytes was increased. Basement membrane of capillaries was frequently increased in width, sometimes irregularly, and in other instances it was reduplicated. In transversely sectioned capillaries lumen diameter was reduced and wall thickness was increased, although total diameter was unchanged. In hypertensive patients the finding of some degenerated capillaries adjacent to muscle fibers could be interpreted as the beginning of a process of rarefaction. Some capillaries showed morphological changes, and the ratio wall thickness/lumen was increased.

Adenosine Triphosphatases↗

Malignant rhabdoid tumor beside benign skin mesenchymal neoplasm with myofibromatous features.

Only a few reports of primary cutaneous rhabdoid tumors have been published. We describe the case of a 3-month-old female patient who developed a rhabdoid type cutaneous sarcomatoid neoplasm in her upper back, close to a benign myofibromatous proliferation of infancy. The lesion was studied both by light microscopy and immunohistochemically. Flow cytometry was performed showing a DNA diploid profile of the malignant tumor. The pathological findings suggest a mesenchymal origin (hemangiopericytic or myofibroblastic type) for both tumors. The patient was surgically treated, but she died nine months later.

Biomarkers, Tumor↗

[Effectiveness educational programs for school dental health. Experimental trial].

This paper is a limited-scope experimental study to evaluate the effectiveness of the Dental Health Educational Programs implemented in Venezuelan schools by the Dentistry Division of the Ministry of Health and Social Welfare. Two hundred and ninety-six six-to-twelve year olds were randomly selected from two schools, one private, the other public, located in the Municipality of Maracaibo, State of Zulia, Venezuela. The children assigned to each school were randomly distributed among the experimental and control groups. A general hypothesis was set up, stating that reinforcement and motivation generate changes in the gingival health of the children under study, but with different results for each, depending on their psycho-social characteristics. Two approaches were used: instruction/supervision and instruction/supervision/reinforcement/stimulation. These two approaches were then measured against a "psycho-social profile" which is based on material conditions and the developmental stages of the children. Instructions were given to the experimental group on how to brush their teeth. They were supervised, reinforced and stimulated for a period of six months, with a post-test assessment. The control group was only given instructions on how to brush their teeth and supervised. A scale based on Massler's classification was used to determine the developmental stages. Standardized indices were used to evaluate the dependent variable: Plaque Index and Gingival Index. The results showed that: the material living conditions and developmental stage of the child are elements that influence the assimilation of pre-established behavior, the basis of preventive programs.

Child↗

Inactivity changed fiber type proportion and capillary supply in cat muscle.

The effect of different levels of activity on fiber types, capillaries and enzymes of gastrocnemius and soleus muscles was studied in two groups of cats. The first group was successfully kept in a large room, exercised on a treadmill 15 min daily 5 days per week and kept in individual small cages. Each period lasted 6 weeks. A muscle biopsy was taken after each period. The second group was formed by cats that were caged for over 20 months. In the group caged for over 20 months, gastrocnemius muscle showed higher IIB and lower I fiber type proportion. Fiber cross-sectional area was not different in any condition. All capillary measurements were significantly lower in gastrocnemius muscle of long-term caged cats, and capillaries per mm2 were lower in soleus muscle of these cats. Exercise increased capillary/fiber in soleus muscle but subsequent caging did not reduced it. In soleus muscle, beta-hydroxy-acyl-CoA dehydrogenase levels decreased after the cage period and hexokinase levels increased after the exercise and decreased after the cage period. In conclusion, different levels of activity for short time produced enzyme changes in soleus muscle, whereas long-term inactivity changed fiber type proportion in gastrocnemius muscle and reduced capillary supply.

3-Hydroxyacyl CoA Dehydrogenases↗

[Cardiac failure secondary to hypoparathyroidism. An unusual presentation].

The case of a 37 year old woman with hypoparathyroid congestive heart failure (CHF) is reported. Thyroidectomy had been performed eight years earlier and she had experienced symptoms of hypocalcemia postoperatively. CHF improved rapidly and completely with the treatment of hypocalcemia. Good prognosis is emphasized but it is necessary to think about this cause of ventricular dysfunction in a patient with CHF and a history of neck surgery in order to make an early diagnosis. Pathogenic mechanisms and differential diagnosis are discussed.

Adult↗

Capillary and muscle fiber type changes in DOCA-salt hypertensive rats.

BACKGROUND: Discrepancies concerning the effect of hypertension on capillaries and muscle fiber types in skeletal muscle have been reported. This study demonstrates the effects of hypertension produced by deoxicorticosterone acetate (DOCA) and salt load on the extensor digitorum longus (EDL) and soleus muscles of the rat. METHODS: Hypertension was produced by subcutaneous injections of DOCA and supplemented with drinking 1% NaCl solution. One group was treated for 7 weeks and another for 14 weeks. Fiber types were classified by ATPase reaction at pH 4.35, capillaries were counted in alpha-amylase-PAS-stained sections, and ultrastructure was studied by conventional methods of transmission electron microscopy. RESULTS: In the 7-week group, a decrease in the percentage of IIA, with an increase in IIB and I fiber types, was found in the EDL muscle. Capillary density was not reduced, but endothelial cells showed surface infoldings into the lumen. Altered mitochondria and an infiltrate of macrophages was present in pericytes. In the 14-week group, a decrease in capillary to fiber index was found in both soleus and EDL muscles. EDL fiber type changes were the same as at 7 weeks. The soleus muscle showed an increased percentage of type I fibers. Some capillaries were degenerated, and others showed an increase in the endothelial cell area covered with pericytes, which resembled smooth muscle cells. CONCLUSION: Hypertensive rats showed changes in the percentage of fiber types in the soleus and EDL muscles. Capillaries adjacent to muscle fibers were reduced and showed morphological changes that resembled arterioles.

Adenosine Triphosphatases↗