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Biomedical subjects

B Gallego

Publications and source records attributed to B Gallego.

15 recordsLinked to original sources

Renal fibrosis in diabetic and aortic-constricted hypertensive rats.

To assess if the renal damage observed in rats with diabetes and hypertension is due to hemodynamic or metabolic changes, a progressive aortic constriction between the two renal arteries has been done in streptozotocin-induced diabetic rats (constriction + diabetes group) and in nondiabetic rats (constriction group). This model allows us to study two kidneys subjected to different perfusion pressure (PP) in the same metabolic environment. One-month-old rats (100-120 g body wt) were subjected to the aortic constriction procedure. Three months after constriction, glomerular filtration rate and renal plasma flow were similar in both kidneys of the two groups. PP was greater in the kidney placed over the ligature [constriction high-pressure kidney (CH) or constriction + diabetic high-pressure kidney (DH)] than in the one placed below the ligature [constriction low pressure (CL) or constriction + diabetic low pressure (DL)]. Proteinuria was higher in the CH than in the CL kidneys (512 +/- 61 vs. 361 +/- 38 microg/30 min, respectively) and much higher in the DH kidney (770 +/- 106 microg/30 min). Renal fibrosis was measured in tissue sections stained with Syrius red using a computer-assisted image analysis system. DH and DL kidneys showed higher corpuscular cross-sectional and capillary tuft areas than the CH and CL ones. The DH kidney showed slight mesangial expansion and thickening of the capillary walls, which were more pronounced in the former. Most renal corpuscles from CH and DH groups were nearly normal in morphology appearance, and only in some instances a slight increment in mesangium was observed. Transforming growth factor-beta1 (TGF-beta1) immunostaining revealed that DH kidneys showed the highest glomerular expression. We concluded that 1) diabetic animals develop glomerular but not interstitial fibrosis to a greater extent than nondiabetic animals and that this lesion principally occurs in the hypertensive kidney (DH), and 2) increased TGF-beta expression is associated with diabetic renal damage.

Animals↗

Inspiratory capacity, dynamic hyperinflation, breathlessness, and exercise performance during the 6-minute-walk test in chronic obstructive pulmonary disease.

Patients with severe chronic obstructive pulmonary disease (COPD) develop dynamic lung hyperinflation (DH) during symptom-limited incremental and constant work exercise with cycle ergometer and treadmill. The increase in end-expiratory lung volume seems to be the best predictor of dyspnea. Quantification of DH is based on the relatively complex use of on-line measurement of inspiratory capacity (IC) from flow volume loops. We reasoned that DH could occur during daily activities such as walking, and that it could be simply measured using the spirometrically determined IC. We studied 72 men with COPD (FEV(1) = 45 +/- 13.3% predicted). IC was measured at rest and after a 6-min walk test. Exertional dyspnea was evaluated using the Borg scale and dyspnea during daily activities with the modified Medical Research Council (MRC) scale. IC decreased significantly from 28.9 +/- 6.7% TLC at rest to 24.1 +/- 6.8% TLC after exercise (p < 0.001). Exertional dyspnea correlated with DeltaIC (r = -0.49, p < 0.00001) and baseline MRC (r = 0.59, p < 0.00001). In many patients with COPD, walking leads to DH that can be easily determined with simple spirometric testing. DH helps explain exercise capacity limitation and breathlessness during simple daily activities.

Activities of Daily Living↗

Effect of chronic and progressive aortic constriction on renal function and structure in rats.

The purpose of this study was to evaluate the functional and structural renal damage observed in aortic-constricted hypertensive rats and to identify their possible relationship with transforming growth factor beta (TGF-beta) expression. Progressive renovascular hypertension was induced by progressive aortic constriction between the two renal arteries. Three months after constriction, the glomerular filtration rate (GFR), effective renal blood flow (ERBF), perfusion pressure (PP), urinary protein excretion (UPE) and urinary electrolyte excretion (U(Na)V and U(K)V) in the kidney above (right kidney, RK) and below the ligature (left kidney, LK) were measured. The cross-sectional corpuscular, capillary tuft and mesangial matrix area and tubulo-interstitial fibrosis were measured in tissue sections stained with Syrius Red using a computer-assisted image analysis system. TGF-beta was detected by immunohistochemistry. The functional parameters were similar in the two kidneys of aortic-constricted hypertensive rats (GFR-RK, 1.33+/-0.08 vs. LK, 1.18+/-0.08 mL/min; ERBF-RK, 9.23+/-1.32 vs. LK, 8.18+/-0.91 mL/min; RVR-RK, 28.3+/-3.9 vs. LK, 21.7+/-3.2 mmHg x min/mL). The RK was subject to a higher PP than the LK (176+/-7 vs. 128+/-5 mmHg, P < 0.05). UPE, U(Na)V, and U(K)V were greater in the RK than in the LK (UPE-RK, 512+/-61 vs. LK, 361+/-38 microg/30 min, P < 0.05; U(Na)V-RK, 0.056+/-0.012 vs. LK, 0.022+/-0.006 mEq/30 min, P < 0.05; UKV-RK, 0.042+/-0.006 vs. LK, 0.029+/-0.003 mEq/30 min, P < 0.05). Morphometric analysis revealed that the RK capillary tuft area and mesangial matrix area were higher than those in the LK. The LK had a higher degree of interstitial fibrosis than the RK. No significant differences in TGF-beta immunostaining were observed between the RK and the LK. In conclusion, the RK (subjected to hypertension) of aortic-constricted hypertensive animals developed glomerular fibrosis, only in the outer glomeruli whereas the LK developed mild interstitial fibrosis. Neither glomerular nor interstitial fibrosis seem to be responsible for the proteinuria observed in both kidneys.

Animals↗

Effect of chronic NG-nitro-L-arginine methyl ester (L-NAME) on blood pressure and renal function in conscious uninephrectomized spontaneously hypertensive rats.

We have studied during 30 days the effect of a low dose of NG-nitro-L-arginine methyl ester (1 mg.kg-1.day-1 in drinking water) in the presence of D- or L-arginine (1 mg.kg-1.day-1 in drinking water) in comparison with D- or L-arginine alone on blood pressure and renal function in conscious uninephrectomized female spontaneously hypertensive rats. At the end of the study, there was a significant increase in systolic blood pressure in the NG-nitro-L-arginine methyl ester + D-arginine group (307 +/- 6 mmHg (1 mmHg = 133.3 Pa), n = 14, p < 0.05) in comparison with NG-nitro-L-arginine methyl ester + L-arginine (281 +/- 6 mmHg, n = 14), L-arginine (262 +/- 5 mmHg, n = 13), and D-arginine (258 +/- 7 mmHg, n = 12) groups. There were no changes in diuresis, proteinuria, or sodium and potassium excretion between differently treated animals during this study. These results suggest that in uninephrectomized female spontaneously hypertensive rats, after 1 month blockade of NO synthesis with a low dose of NG-nitro-L-arginine methyl ester, vasculature is under tonic control by NO and it is not correlated with renal dysfunction.

Animals↗

Renal effects of antihypertensive therapy in uninephrectomized diabetic rats.

Diabetic nephropathy is a major cause of chronic renal failure. The evidence available indicates that renal hemodynamics are altered in clinical and experimental diabetes mellitus. In these circumstances, an increased glomerular filtration rate (GFR) is associated with albuminuria and eventually with glomerulosclerosis. We studied the renal and hemodynamic effects of long-term treatment (5 months) using an angiotensin-converting enzyme inhibitor (trandolapril, 0.7 mg/g b.w. per day) and a calcium antagonist (verapamil, 20 mg/g b.w. per day), and the combination of the two (veratran) at the same dose, on streptozotocin-diabetic uninephrectomized rats. A moderate degree of hyperglycemia (2-4 g/l) was maintained with daily insulin. Mean arterial pressure (MAP) was measured monthly using the tail-cuff method. Determinations were made of urinary protein excretion, creatinine clearance, urinary electrolyte excretion and, at the end of treatment, renal and cardiac hypertrophy. MAP was similar in control and untreated diabetic rats. Trandolapril and veratran reduced MAP whereas verapamil alone had no effect on these animals. All groups showed a slight proteinuria that increased with verapamil treatment. The GFR of diabetic animals was higher than in the control group (mainly the first 2 months), except for veratran group, in which it was similar to the control value. Urinary electrolyte excretion increased in all diabetic groups with no significant differences among them. Veratran induced a protective effect against cardiac hypertrophy. None of the treatments affected renal hypertrophy. It is concluded that in a murine model of diabetes without hypertension or proteinuria, a combination of verapamil and trandolapril prevents hyperfiltration whereas verapamil alone increases proteinuria.

Angiotensin-Converting Enzyme Inhibitors↗

Role of atrial natriuretic factor, hemodynamic changes and renal nerves in the renal effects of intraperitoneal morphine in conscious rats.

The aim of the present study was to investigate the role of renal nerves and atrial natriuretic factor (ANF) in the mechanisms responsible for the diuresis and antinatriuresis induced by morphine in rats in a normal state of hydration. Male Wistar rats weighing 350-400 g were divided into two groups: one group was subjected to bilateral renal denervation, whereas the other consisted of sham-operated controls. The animals were placed in individual metabolic cages, and morphine (1.25, 2.5, 5.0 or 10.0 mg/kg body weight) or vehicle (0.5 ml isotonic saline) was injected intraperitoneally. Urine was collected hourly for 1 h before and 3 h after morphine injection. The lower doses of morphine (1.25 and 2.5 mg/kg body weight) induced a transient increase in urine output (from 1.17+/-0.12 to 2.49+/-0.34 and from 0.78+/-0.08 to 1.71+/-0.18 microl/min, respectively). The diuretic response to these doses was similar in bilaterally denervated rats. Higher doses (5.0 and 10.0 mg/kg body weight) induced a marked but transient reduction in the urinary flow rate during the first hour (from 0.90+/-0.11 to 0.48+/-0.05 and from 1.37+/-0.17 to 0.45+/-0.08 microl/min, respectively), followed by a delayed diuretic effect. The antidiuretic action of morphine was not observed in bilaterally denervated rats. In control rats, morphine induced a dose-dependent decrease in sodium excretion 1 h after administration, an effect that was blunted in the denervated group. The lower morphine doses (1.25 and 2.5 mg/kg body weight) elicited a transient increase in the glomerular filtration rate (GFR) in both control (from 1.23+/-0.12 to 1.67+/-0.17 and from 1.28+/-0.14 to 2.41+/-0.18 ml/min) and bilaterally denervated rats (from 1.29+/-0.14 to 1.66+/-0.17 and from 1.18+/-0.22 to 1.72+/-0.19 ml/min), whereas the higher doses (5.0 and 10.0 mg/kg body weight) produced a marked, transient GFR decrease in the controls (from 1.25+/-0.11 to 0.43+/-0.05 and from 1.13+/-0.17 to 0.47+/-0.08 ml/min) and bilaterally denervated animals (from 1.48+/-0.16 to 0.74+/-0.09 and from 1.22+/-0.15 to 0.73+/-0.06 ml/min), although the reduction was less pronounced with renal denervation. Morphine induced a transient, dose-dependent reduction in blood pressure (from 114+/-1 to 71+/-6 mm Hg at 10.0 mg/kg body weight) and a dose-dependent elevation of plasma ANF. No differences in plasma ANF were observed between control and denervated animals under basal conditions (60+/-7 vs. 42+/-6 pg/ml) or after injection of 2.5 or 5.0 mg/kg of morphine (155+/-11 vs. 167+/-9 and 360+/-9 vs. 401+/-9 pg/ml, respectively). Our data suggest that the renal responses to intraperitoneal morphine administration derive from the integration of several different actions: (1) increased ANF release; (2) decreased arterial pressure; (3) subsequent activation of renal sympathetic activity, and (4) the direct effect of morphine on tubular function.

Analgesics, Opioid↗

Tobacco smoke and age as risk factors in emphysema. Morphometrical study on the rat.

During ageing, a progressive deterioration in the pulmonary function, which can be accelerated by exposure to tobacco smoke, takes place. The hypothesis that the initial age of exposure to tobacco smoke is a factor of utmost importance in the development of emphysema is proposed. Eighty-six rats, aged nineteen months at the time of sacrifice, were used and were ordered into three groups: the first group consisted of unmanipulated animals; the second, of animals which had been exposed to tobacco smoke from the age of twelve months to the age of nineteen months; and the third, of animals which had been exposed to tobacco smoke from the age of nine months to the age of twelve months. The lungs of the animals were histologically processed for light microscopy and were studied morphometrically by computer. Eleven quantitative variables were quantified and ordered into three groups: variables related with alveolar enlargement; variables related with tissue loss; and variables related with the elastic fibre. The number of animals in which alveolar enlargement and tissue destruction concurred was counted, thus enabling the attributable and relative risks of developing emphysema to be calculated in the two groups of manipulated animals. From the results it is clear that, when compared with the unmanipulated group, the two groups which had been exposed to tobacco smoke displayed an increase in the variables which quantified alveolar enlargement and a decrease in those which measured tissue loss; these results were more significant in the third group (p < 0.001) than in the second (p < 0.05); significant differences were also found between these two groups of animals. The relative risk and attributable risks of developing emphysema were 2.41 and 28.15 respectively in the second group and 3.48 and 34.48 in the third group. Our results lead us to propose that the risk of developing emphysema exists in inverse proportion to the initial age of exposure to tobacco smoke.

Aging↗

Age and experimental obstructive emphysema. A morphometrical study on the rat.

Age, as a risk factor in the development of experimental obstructive emphysema, is proposed as the hypothesis of this study. Ninety-two Wistar rats were organized into two age groups: adult (16 weeks) and middle-aged (56 weeks). Each age group was subdivided into three groups: a control group, consisting of unmanipulated animals; a "cannula" group consisting of animals into whose trachea a cannula was implanted; and a "valve" group, consisting of animals into whose trachea a valve had been implanted. The survival was one month. A histomorphometric study was performed on the lungs and the results were compared statistically. Throughout the experiment the amount of food consumed by each animal and the variations in weight were monitored. After sacrifice, the lungs were processed for light microscopy. Thirteen histomorphometric variables were quantified and subsequently systematized into three groups: those which quantified the size of the distal airspace ("area of the alveolar section", "alveolar chord" and "mean linear intercept"): those which quantified the tissue ("wall thickness", "tissue density", "internal perimeter of each alveolar section", "internal alveolar perimeter per field" and "alveolar section/section perimeter"); and those which quantified the elastic fibre ("elastic fibre area", "elastic fibre perimeter", "elastic fibre area/elastic fibre perimeter", "elastic fibre density" and "elastic fibre density per tissue density"). The results were compared statistically and the sensitivity, specificity and misclassification indices were calculated, as well as the attributable and relative risk. From the results, it was observed that, in general, the animals of the valve and cannula groups in both age groups displayed a decrease in food intake and a body weight loss. The middle-aged animals were the only group which displayed significant differences in all the morphometric variables except wall thickness, when the cannula and valve groups were compared with the control group. In both the cannula and valve groups, the values of the variables which quantified the distal airspace increased, while the values of the variables which quantified the lung tissue and the elastic fibre decreased. In the manipulated middle-aged group, the attributable risk of developing emphysema was 56.66% and the relative risk 5.55; in the group of manipulated adult animals, the attributable risk was 23.55% and the relative risk 1.66. The results of this study lead us to propose that the middle-aged rats with experimental airflow obstruction displayed a greater risk of developing emphysema than the adult rats which were subjected to the same procedure.

Aging↗

Changes occurring with increasing age in the rat lung: morphometrical study.

BACKGROUND: It was hypothesized that the evolution towards the senile lung is progressive, being initiated in the adult stage; and for this reason changes similar to those described in the senile lung can be detected in the lungs of middle-aged rats. To test the hypothesis, the following design was used. The lungs of two groups of rats, adult (mean age of 16 weeks) and middle-aged (mean age of 56 weeks) were morphometrically compared. METHODS: Thirty-one Wistar rats were used for the study; their lungs were processed histologically. The microscopic fields were analysed in a computer, and 20 variables were quantified. These were grouped into a) variables which describe the shape and size of the distal airspace, b) variables which describe the distal lung tissue, and c) variables which describe elastic fibers. The results were statistically compared: correlation tests were carried out, and the specificity, sensitivity, and misclassification indices were calculated. RESULTS: All the results of the variables which define the size of the airspaces were found to be significantly higher (P < 0.0001) in the middle-aged animals; the results obtained when the lung tissue was quantified directly from the histological section suggested a loss of tissue in the middle-aged animals. However, when these data were converted into absolute values, no loss was indicated in the total lung tissue. The values of the variables which describe the elastic fiber were found to have increased significantly (P < 0.0001) in the middle-aged animals. The misclassification index was found to be lower than 10% in six variables and between 10% and 20% in four. CONCLUSION: The low misclassification indices found lead us to consider that our morphometric method is ideal for distinguishing the lungs of the two groups of animals used. The results of the quantification of the variables show that the middle-aged animals exhibit simple enlargement of the distal airspaces, without tissue loss, which coincides with the current definition of the senile lung.

Aging↗

Pulmonary response to bovine albumin. A morphometric study in rats.

The following hypothesis is proposed: that hypersensitivity pneumonitis (HP), experimentally induced in rats, is the cause of a thickening in the alveolar wall, a decrease in the size of the alveole, hyperplasia in the bronchus-associated lymphoid tissue (BALT) and hypertrophy in the goblet cells. Wistar rats were classified into two different groups, namely, non-treated animals and animals exposed to bovine albumin (BA). A morphometric study was carried out and the following variables were quantified: a) percentage of lymphocytes, neutrophils and alveolar macrophages of the bronchio-alveolar lavage (BAL); b) the interstice of the alveole, the alveolar chord length, the alveolar wall thickness and the number of alveolar macrophages with hemosiderin within its cytoplasm; c) the size of lymphatic area (LA) in BALT, the length of the lymphatic epithelium (LEp) in BALT and the percentage of goblet cells in the bronchial epithelium. The following results were obtained from the animals exposed to BA: 1) a significant increase in both lymphocytes and neutrophils of BAL, and of alveolar macrophages with hemosiderin in its cytoplasm; 2) a significant thickening of the alveolar walls and the BALT elements, which confirms the above mentioned hypothesis; 3) a significant increase in the alveolar chord and a significant decrease in the number of goblet cells of the bronchus, which contradicts the above mentioned hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolitis, Extrinsic Allergic↗

[The hepatotoxicity of tuberculosis treatment].

BACKGROUND: The hepatic toxicity of antituberculous drugs used for the therapy of initial cases was evaluated, assessing the incidence and severity and its relation with each drug, age, other associated hepatic risks and the chronological time of therapy. METHODS: 1235 patients with tuberculosis were prospectively assessed with a protocol including periodical clinical and laboratory controls. RESULTS: Hepatic toxicity was found in overall 16.5%, with 3.5% of severe forms and need for a definitive change in therapy in 1.5%. Differences in toxicity between the 6-month and the 9-month schedules were not found. The most commonly incriminated drugs was isoniazid followed by pyrazinamide. All severe forms presented with symptoms, although some were nonspecific and insidious. Other associated hepatic risks implied an increased frequency of iatrogenic reactions. Age did not have a determining influence in severe forms, which predominantly developed within the first two months of therapy. CONCLUSIONS: Moderate, transient and asymptomatic increase in transaminase activity not requiring a change a therapy is common. Severe and dangerous forms are uncommon and predominate at the beginning of therapy and in persons with associated hepatic risk factors. Therefore, although the clinical controls should be maintained throughout treatment, laboratory controls should only be carried out during the first two months, except when symptoms are present or in patients with associated hepatic risk factors, where they should be more frequent and carried out throughout treatment.

Age Factors↗

[Replacement therapy of emphysema caused by alpha 1-antitrypsin deficiency].

The most common feature of alpha1-antitrypsin (alpha 1 AT) deficiency is pulmonary emphysema, which becomes manifest in the third to fifth life decades in most subjects with PiZZ phenotype. In recent years, replacement therapy with alpha 1 AT from the plasma of blood donors has been developed. We report the protocol of treatment which has begun to be used in our center, now including two patients. We discuss inclusion criteria, the treatment schedules, the adverse side-effects and the future outlook for this type of therapy.

Aged↗

[A morphometric model of hypersensitivity pneumonitis in the aging rat].

Our objective was to develop an experimental model of hypersensitivity pneumonitis in the aging rat. The following hypothesis was proposed: hypersensitivity pneumonitis in the aging rat will be evident in alterations in cells harvested by bronchoalveolar lavage (BAL) and in an increase in alveolar interstitial tissue. Sixty animals with a mean age of 18 months were divided into 2 groups. Group 1 contained healthy, untreated animals and group 2 contained unhealthy animals that had been exposed to bovine seralbumin (BS). BAL and morphometric analysis of the lung was performed. The percentage of lymphocytes, polymorphonuclear, leukocytes and alveolar macrophages were determined in BAL. The morphometric variables studied were mean linear intersection (Lm), length of alveolar cord, wall thickness, tissue density and number of measurements of alveolar cord. The results show that the unhealthy animals had higher (p < 0.001) percentages of lymphocytes in BAL, lower Lm, diminished alveolar cord and thinner walls, as well as greater tissue density and a higher number of measurements. All differences were statistically significant (p < 0.001). These results lead to the conclusion that exposure of the aging rat to BS produces an increase in lymphocytes in BAL and an increase in interstitial alveolar content, findings that are related to alveolar-interstitial inflammation.

Aging↗

Beneficial effect of the long-term treatment with the combination of an ACE inhibitor and a calcium channel blocker on renal injury in rats with 5/6 nephrectomy.

The effects of the addition of a calcium channel blocker, verapamil (20 mg/kg/day) to an ACE inhibitor, trandolapril (0.7 mg/kg/day) in a 6-month treatment on renal insufficiency development in rats with 5/6th nephrectomy, were studied. Every month we measured heart rate and arterial pressure by the tail-cuff method. Renal function studies were performed in metabolic cages. At the end of the study, renal tissue was prepared for light microscope analysis. Renal lesions were assessed by semiquantitative scores in a blind fashion. Corpuscular section area, intraglomerular and tubulointerstitial fibrosis were determined by digital image analysis with a specific software (Fibrosis HR) on syrium red-stained renal sections. Trandolapril markedly increased the survival ratio that after 6 months reached 87% in comparison with 61% in untreated rats. No mortality was observed in rats treated with the combination of verapamil and trandolapril. Trandolapril treatment prevented the development of hypertension. The combination verapamil-trandolapril did not induce further reduction on blood pressure. The untreated group showed a marked proteinuria, that in the trandolapril group showed an important reduction. The verapamil + trandolapril group showed a proteinuria significantly smaller than that of all the other groups. Light microscopy semiquantitative studies of the renal injury showed that the trandolapril and verapamil + trandolapril groups had a marked reduction in glomerular and tubulointerstitial alterations, compared with untreated animals. Quantitative determinations of glomerular and interstitial fibrosis performed on syrium red-stained renal sections demonstrated that fibrosis was reduced when rats when treated with trandolapril and even more with verapamil + trandolapril when they were compared to untreated animals' values. In conclusion, long-term treatment with verapamil given in addition to trandolapril produces additional protection against progressive renal injury associated to subtotal nephrectomy.

Angiotensin-Converting Enzyme Inhibitors↗