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A Molteni

Publications and source records attributed to A Molteni.

117 records · Page 7Linked to original sources
PubMedDate not supplied

Effect of acute smoke inhalation on angiotensin converting enzyme, plasminogen activator, and angiotensin-II in the dog.

Smoke inhalation injuries in humans are associated with many uncontrolled variables which impact on the lung and make the cause of the pulmonary response difficult to assess. In this report, an established model of smoke inhalation injury in the dog was used to study the early responses of tissue and serum angiotensin-converting enzyme (ACE), tissue plasminogen activator (PLA), and plasma angiotensin II. Animals were exposed to smoke from burning sawdust and kerosene for five minutes. The hemodynamic and pulmonary mechanical responses were typical with a rise in pulmonary artery pressure, pulmonary vascular resistance, and venous admixture (shunt fraction) while dynamic compliance fell. Within five minutes of smoke exposure, lung ACE declined without any change in serum ACE. Lung PLA dropped one hour after injury. Plasma angiotensin II increased within 30 minutes without evidence for systemic hypertension. These early enzymatic changes substantiate the presence of pulmonary endothelial damage known to occur in this form of chemical injury. These changes may condition the lung's physiologic response to the injury and to additional stresses which are multiple when smoke inhalation occurs in conjunction with a cutaneous burn.

Angiotensin II↗
PubMedDate not supplied

Monocrotaline-induced cardiopulmonary injury in rats: modification by the nonthiol ACE inhibitors CGS13945 and CGS16617.

Thiol angiotensin converting enzyme (ACE) inhibitors (Captopril, CL242817) and collagen antagonists (D-penicillamine) partially prevent pulmonary hypertension in monocrotaline-treated rats. The purpose of the present study was to determine whether the nonsulfhydryl ACE inhibitors CGS13945 and CGS16617 also ameliorate monocrotaline-induced cardiopulmonary damage in rats consuming the drugs continuously for 6 weeks. D-penicillamine was tested concomitantly as a positive control. Monocrotaline-treated animals developed severe pulmonary histopathology occlusive wall thickening of the pulmonary arteries, adrenomegaly, cardiomegaly, and right heart enlargement. Concomitant administration of CGS13945, CGS16617, or penicillamine ameliorated most of these monocrotaline reactions. Monocrotaline-induced histopathologic changes in the lung were accompanied by pulmonary endothelial dysfunction, including suppressed ACE and plasminogen activator activity and increased prostacyclin and thromboxane production. None of the modifying agents influenced these functional abnormalities in monocrotaline-treated lung endothelium. Thus, the ACE inhibitors CGS13945 and CGS16617 ameliorate monocrotaline-induced cardiopulmonary damage in rats, indicating that the presence of a thiol group is not essential for this class of compounds to exhibit therapeutic activity against monocrotaline lung injury. The present data do not identify the mechanism of action of CGS13945 and CGS16617, but appear to rule out lung ACE inhibition and lung endothelial cell sparing as major therapeutic factors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Serum copper concentration as an index of cardiopulmonary injury in monocrotaline-treated rats.

The pyrrolizidine alkaloid monocrotaline produces pulmonary inflammation, hemorrhage, fibrosis, and hypertension. In rats, monocrotaline pneumotoxicity can be ameliorated by cotreatment with inhibitors of angiotensin converting enzyme (ACE), such as CL242817. In the present study, serum and urine copper (Cu) concentrations were evaluated as indices of cardiopulmonary injury in rats sacrificed after six weeks of continuous administration of monocrotaline (0 to 3.6 mg per kg per day, in the drinking water) or CL242817 (60 mg per kg per day, in the feed), or both. Monocrotaline-treated rats exhibited dose-dependent increases in (1) pulmonary histopathology, (2) pulmonary endothelial dysfunction (decreased lung plasminogen activator activity, and increased prostacyclin and thromboxane production), (3) pulmonary hydroxyproline (collagen) content, and (4) cardiac right ventricular hypertrophy (an anatomic correlate of pulmonary hypertension). The severity of cardiopulmonary damage was accompanied by a dose-dependent elevation in serum Cu concentration. Serum iron concentration, in contrast, did not change. Urinary Cu concentration correlated roughly with that of serum, but the variability within groups was high. Cotreatment with the ACE inhibitor CL242817 not only ameliorated monocrotaline-induced right heart enlargement and lung hydroxyproline accumulation but also reduced the hypercupremia in monocrotaline-treated rats. Thus, serum copper concentration appears to be an accurate and minimally invasive index of monocrotaline pneumotoxicity in this model of pulmonary hypertension.

Animals↗
PubMedDate not supplied

Estradiol receptor assays in normal and neoplastic tissues. A possible diagnostic acid for tumor differentiation.

Estradiol (E2) binding activity was studied in several normal tissues and neoplasias of humans and experimental animals. Positive E2 binding was seen in 37 percent of breast primary malignancies, 50 percent of breast cancer metastasis to other organs, and 55 percent of breast cancer metastasis to lymph nodes. Two other tumors, renal cell carcinomas and thyroid adenocarcinomas, also had a high percent of E2 binding activity. No difference was evident histologically between the tumors which were positive and those which were negative. Elevated E2 binding activity was seen in normal liver and pancreas of rats and mice as well as in an experimentally induced acinar pancreatic carcinoma of the rats. These preliminary results indicate that the measurement of estradiol receptors should be extended to other neoplasias than breast cancer, and it may give some indication about the evolution and the hormonal controls of the tumors themselves.

Adrenal Gland Neoplasms↗
PubMedDate not supplied

Circadian rhythms of serum aldosterone, cortisol and plasma renin activity in burn injuries.

Circadian rhythm of serum aldosterone and cortisol concentrations and of plasma renin activity (PRA) were measured by radioimmunoassay in 10 adults with thermal injuries. The determinations were begun 6 to 48 hours after the injury and continued for five consecutive days four times a day. In all patients, the normal pattern of the circadian rhythm for all three hormones disappeared and values remained quite high at any time of the day or the night. Four patients developed an hypertensive crisis with quite elevated levels of aldosterone, cortisol and plasma renin activity. The same hormones were also found very elevated in two hypotensive patients with 80 percent or more of injured body surface who were in agonal conditions and succumbed to the injury.

Adult↗
PubMedDate not supplied

Effect of wood combustion smoke inhalation on angiotensin-1-converting enzyme in the dog.

One lung of each dog was exposed to smoke from burning pine wood, while the other was subjected to acute hypoxia. Angiotensin-1-converting enzyme (ACE) activity in biopsied tissue of the smoke-exposed lung was markedly increased immediately after the injury and even higher 30 minutes later. No change in ACE activity was observed in the hypoxic contralateral lung. Serum ACE activity did not change significantly following anesthesia and before smoke inhalation. Serum aldosterone and cortisol levels increased at this juncture. Smoke inhalation caused intra-alveolar hemorrhages and edema. Pulmonary and systolic, diastolic and mean pressures, pulmonary capillary, wedge pressure, cardiac output and systemic and pulmonary arteriolar resistances remained unchanged throughout the experiment. The changes of ACE activity are presumably a direct effect of smoke inhalation. They are seen as an early response of the lung endothelial cells to many types of injury (chronic hypoxia, bleomycin or monocrotaline administration) and may represent an important step in the development of the organ's response to the injury.

Aldosterone↗
PubMedDate not supplied

Considerations of the renin-angiotensin aldosterone system in the pathogenesis of hypertension in infancy.

Studies with school aged children of several communities of the United States have indicated that between one and two percent of them should be considered hypertensive. These findings contradict previous statements of a very rare incidence of hypertension in childhood. Some studies show that children of Black and Hispanic American ancestry, especially females, have a higher incidence of hypertension. The highest incidence of hypertensive children was related to a history of familial hypertension and obesity. In children less than three years of age and in infants, hypertension is less frequent. A disease of the urinary apparatus (nephropathy) or of the cardiovascular system (aorta coarctation) can often be identified as the primary cause of the hypertension. Less frequent is hypertension sustained by adrenal cortical dysfunction or a neoplasm of the adrenal medulla. Hypertensive crisis also frequently develops in children after thermal injury or renal transplant. In children, the use of antihypertensive drugs should be reserved for cases where the disease is very severe. Effective regulation of dietary and hygienic habits should be recommended, particularly for those cases of "mild" or "borderline" essential hypertension.

Adrenocortical Hyperfunction↗
PubMedDate not supplied

Early markers of ventilator-induced lung injury in rats.

Positive pressure ventilation with hyperdistention of the lungs (PPVHDL) causes microscopic lung injury in rats and in mice. This study compared lung lavage and serum levels of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatinine phosphokinase (CPK), lung lavage and plasma endothelin-1 (ET-1) concentration, lung tissue ET-1 mRNA expression, angiotensin converting enzyme (ACE) activity of lung homogenates, and histology of the lung structure in control and PPVHDL rats. Rats were anesthetized with pentobarbital. While control rats were breathing spontaneously, the PPVHDL rats were ventilated with a rodent ventilator delivering 30 percent oxygen, a tidal volume of 18.6 +/- 4.5 ml/kg, and a respiratory rate of 55 to 60 per minute. End-tidal CO2 was maintained at 38-40 mm Hg. After seven hours, rats were killed and the lungs were lavaged. Red blood cells were present in the sediment of lavage fluid in PPVHDL rats and their lung structure showed severe congestion, alveolar septa filled with red cells, and extravasation of red blood cells and inflammatory cells into the alveolar space. Lung lavage fluid AST and LDH were significantly higher in the PPVHDL compared with the control group (P < 0.03 and P < 0.001, respectively). Electrophoresis of the lung lavage LDH showed increased peak-5 in the PPVHDL group. Serum LDH, CPK, AST, and potassium concentrations [K]+ were significantly higher in the PPVHDL rats whereas their serum total protein level was significantly lower than the control group (P < 0.001). Electrophoretic patterns of serum and lung lavage protein were similar in both groups indicating a transmural passage of serum protein from the intravascular to the intra-alveolar space. No significant difference was found in lung tissue ET-1 mRNA expression and lung protein concentration between the two groups. Lung ACE activity, in contrast, was significantly lower in PPVHDL rats. This study demonstrated that moderate alveolar hyperdistention caused significant structural lung damage accompanied by decreased ACE activity after seven hours of mechanical ventilation and that elevated lung lavage and serum LDH and AST levels in lung lavage and in serum might be early markers of ventilator-induced lung injury in this rat model.

Animals↗