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A Molteni

Publications and source records attributed to A Molteni.

At least 55 records · Page 3Linked to original sources
PubMed1990

Captopril reduces collagen and mast cell accumulation in irradiated rat lung.

The angiotensin converting enzyme inhibitor captopril ameliorates radiation-induced pulmonary endothelial dysfunction in rats. The present study determined whether captopril also reduces collagen (hydroxyproline) accumulation in the lungs of rats sacrificed 2 months after a range of single doses (0-30 Gy) of 60Co gamma rays to the right hemithorax. Captopril was administered in the feed at a regimen of 0, 25, or 50 mg/kg/day continuously after irradiation. Mast cell counts also were obtained from lungs of all animals exposed to 30 Gy. In rats receiving no captopril, there was a radiation dose-dependent increase in right lung hydroxyproline (HP) content and in HP concentration per g wet weight. Captopril produced a drug dose-dependent suppression in this radiation-induced HP accumulation. At a dose of 50 mg/kg/d, captopril reduced the slope of the radiation dose response curve for lung HP content by a factor of 1.7, and completely prevented the increase in HP concentration. At an isoeffect level of 550 micrograms HP per right superior lobe, this dose of captopril exhibited a DRF of 1.7 +/- 0.2. In rats exposed to 30 Gy, moreover, the number of mast cells per mm2 of alveolar cross-sectional surface area decreased from 105 +/- 8 to 100 +/- 7 and 59 +/- 5 in the groups given 0, 25 or 50 mg/kg/d of captopril, respectively, (vs none in sham-irradiated rats). These data are the first to demonstrate that the ACE inhibitor captopril might provide a novel intervention in the pathogenesis of radiation fibrosis.

Animals↗
PubMed1990

Effect of angiotensin-converting enzyme inhibition on pituitary hormone responses to insulin-induced hypoglycemia in humans.

Renin, angiotensin-II, and angiotensin-converting enzyme (ACE) have been found in the hypothalamus and pituitary in rats, and renin, angiotensinogen, and ACE have been found in human pituitary lactotrophs. To determine the physiological relevance of the renin-angiotensin system in the pituitary hormone response to stress in humans, we created significant inhibition of ACE by administering a clinically used dose (10 mg) of enalapril (E) 4 h before measuring the stress hormone responses to insulin-induced hypoglycemia. Eight fasting lean healthy males (aged 20-35 yr) were given either placebo (P) or E (10 mg, orally) in two studies separated by at least 5 days in a blinded study design. Glucose, ACTH, cortisol, PRL, and GH levels were measured before E or P and at 20-min intervals beginning 20 min before insulin administration. ACE levels were similar at baseline (E, 21.6 +/- 2.7; P, 22.4 +/- 2.4 mU/mL/min), but were significantly lower at the time of insulin injection with E treatment (E, 2.9 +/- 0.5; P, 20.9 +/- 2.5 mU/mL/min; P less than 0.001). The mean of the total area under the curve of PRL secretion was significantly lower for the E group (E, 3767.2 +/- 710.7; P, 4554.9 +/- 650.1 micrograms/L.min; P less than 0.05). Although the mean peak PRL levels were lower for the E group, this did not reach statistical significance (E, 53.0 +/- 9.7; P, 64.4 +/- 9.4 micrograms/L; 0.05 less than P less than 0.10). These differences in PRL responses appeared to be due primarily to substantial decreases in PRL responses with E in three of the eight subjects. No significant differences were found with ACTH, cortisol, or GH for basal levels, peak levels, or areas under the curve.

Adrenocorticotropic Hormone↗
PubMed1990

The effect of Captopril on benign and malignant reactions in irradiated rat skin.

The effect of the angiotensin converting enzyme inhibitor Captopril on the severity of radiation-induced epilation and moist desquamation and the incidence of skin tumours was determined for up to 52 weeks in male rats. The irradiation consisted of a range of single doses (0, 10, 20, 30 Gy) of 60Co gamma rays to a 3.5 cm2 right hemithorax port. Half of each radiation dose group consumed control powdered chow, and half consumed chow containing Captopril (50 mg/kg/day) continuously after irradiation. There were time- and radiation-dose-dependent increases in all three skin reactions. Rats exposed to 10 Gy exhibited a mild and transient epilation, but no moist desquamation or neoplasia in the radiation port. In animals exposed to 30 Gy, however, epilation began at 2 weeks after irradiation, reached a peak at approximately 7 weeks, then persisted essentially unchanged through 52 weeks. Captopril had no significant effect on the epilation reaction. Two waves of moist desquamation were observed after 30 Gy. The first appeared at 3 weeks after irradiation, reached a peak from 6-10 weeks, then subsided partially but significantly from 12-26 weeks. The second wave of moist desquamation began at 26-28 weeks, often was ulcerative, and occasionally was accompanied by the appearance of tumours in the irradiated volume. Captopril significantly (p less than 0.05) reduced the severity of both phases of the moist desquamation reaction after 30 Gy, and reduced the percentage of animals exhibiting the most severe desquamation score (involving 50% of the radiation port). Of particular interest was the observation that Captopril also reduced the incidence of tumours. Of the 14 tumours detected, all were malignant (fibrosarcomas, squamous cell carcinomas), and only three (p less than 0.05) occurred in rats receiving Captopril. Multiple tumours (three cases), tumours induced by 20 Gy (three cases), and tumours appearing before 6 months (one case) were observed only in rats consuming control diet, never in Captopril-treated animals. Animals which developed tumours in the second 6 months post-irradiation exhibited significantly more severe moist desquamation during the first 6 months than did the tumour-free members of their treatment group. Thus Captopril, known to ameliorate acute lung damage in irradiated rats, also reduces chronic benign and malignant skin reactions in the radiation treatment field.

Animals↗
PubMed1989

Monocrotaline-induced cardiopulmonary injury in rats. Modification by the neutrophil elastase inhibitor SC39026.

Rats were killed after 6 weeks of continuous ingestion of the pneumotoxic alkaloid monocrotaline (2.2 mg/kg/day), the neutrophil elastase inhibitor SC39026 (60 mg/kg/day), or both. Pulmonary reactions were evaluated by light and electron microscopy. Lung endothelial function was monitored by angiotensin converting enzyme (ACE) activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Lung hydroxyproline content was measured as an index of interstitial fibrosis. Cardiac right ventricular hypertrophy was determined by the right ventricle to the left ventricle plus septum weight ratio (RV/LV + S). Rats receiving SC39026 alone did not differ significantly from untreated control animals with respect to any of the quantitative endpoints, although rarefaction of Type I pneumocytes was observed in the electron micrographs of these animals. Monocrotaline-treated rats, in contrast, developed a significant increase in RV/LV + S, and exhibited pulmonary edema, inflammation, fibrosis, and muscularization and occlusive mural thickening of the pulmonary small arteries and arterioles. These monocrotaline-induced structural changes were accompanied by decreased lung ACE and PLA activities, and increased PGI2 and TXA2 production, and by an increase in lung hydroxyproline content. Cotreatment with SC39026 ameliorated the monocrotaline-induced pulmonary vascular wall thickening and the cardiac right ventricular hypertrophy. These data suggest that inappropriate neutrophil elastase activity contributes to monocrotaline pulmonary vasculopathy and hypertension. On the other hand, cotreatment with SC39026 had no significant effect on the severity of the monocrotaline-induced lung inflammatory reaction, the pulmonary endothelial dysfunction, or the increase in lung hydroxyproline content.

Animals↗
PubMed1989

Serum copper concentration as an index of clinical lung injury.

The purpose of this ongoing study is to determine whether thoracic radiotherapy for lung cancer produces an early increase in serum copper (Cu) concentration, an increase which might predict clinical outcome. Copper and iron concentrations were measured in serum obtained from nonsmall cell lung cancer patients at 0, 1, 2, 4, and 6 weeks after the start of radiotherapy. Control groups included patients irradiated for breast cancer (low dose of radiation to the lung), for endometrial, cervical or prostatic cancer (no dose to lung), and patients with congestive heart failure, pulmonary hypertension, chronic obstructive pulmonary disease (COPD), and cutaneous burns with or without smoke inhalation (no irradiation). Serum Cu concentration increased at least 10 micrograms/dl from the pretreatment level in approximately 75% of the adenocarcinoma and squamous cell lung cancer patients, but in only 1 of 4 undifferentiated lung cancer cases. In virtually all of these responders, serum Cu increased to a maximum at 2 weeks after the start of therapy, then plateaued or decreased slightly despite continuing irradiation. Within the subset of squamous cell lung cancers, there was a direct correlation between the degree of histologic differentiation and both baseline serum Cu concentration and the probability of an early increase therein. In contrast, only 33% of breast cancer patients and 15% of endometrial, cervical and prostate cancer patients exhibited an increase in serum Cu concentration at 2 weeks after the start of radiotherapy. Serum Cu concentration was within normal limits in virtually all patients with congestive heart failure, pulmonary hypertension, and COPD. Burn patients exhibited a significant reduction in serum Cu, although concomitant smoke inhalation increased serum Cu back to low-normal levels. Serum iron concentration did not change significantly in any category of patients. These data suggest that thoracic radiotherapy for well differentiated non-small cell lung cancer is accompanied by an early increase in serum Cu concentration. This increase is partly but not wholly related to lung dose in particular rather than tissue dose in general, and specifically reflects radiation-induced lung injury rather than pneumopathy in general. In lung cancer patients, the change in serum Cu concentration during the first 2 weeks of radiotherapy exhibits a sufficiently broad range (+60 to -13 micrograms/dl) to permit testing this parameter as a predictor of tumor response and pulmonary complications.

Adenocarcinoma↗
PubMed1989

Serum copper concentration as an index of experimental lung injury.

Serum copper (Cu) concentration was evaluated as an index of lung injury in two rat models of pneumotoxicity: hemithoracic irradiation and monocrotaline ingestion. In both models there was a dose- and time-dependent increase in serum Cu concentration. This hypercupremia paralleled the development of pulmonary endothelial dysfunction (decreased lung plasminogen activator activity and increased prostacyclin production) and pulmonary fibrosis (hydroxyproline accumulation). In the radiation model, lung injury and hypercupremia persisted for at least 6 months, and were spared similarly when the total dose was delivered in multiple daily fractions as compared to single doses. In irradiated rats, the elevated serum Cu concentration was accompanied by increases in plasma ceruloplasmin, lung Cu concentration, and lung Cu/Zn superoxide dismutase (SOD) activity. In monocrotaline-treated rats, lung damage and hypercupremia also were accompanied by a reduction in liver Cu concentration, and by a direct correlation between the concentrations of Cu and SGOT in the serum. In both models, some but not all modifiers of lung damage (penicillamine, angiotensin converting enzyme inhibitors, pentoxifylline) also partially prevented the insult-induced hypercupremia. In contrast, serum iron concentration was largely independent of treatment in all experiments. These data suggest that elevated serum copper concentration is an accurate and minimally invasive index of lung injury in irradiated and monocrotaline-treated rats.

Alanine Transaminase↗
PubMed1989

Monocrotaline pneumotoxicity in mice.

Lung injury induced in rats by the pyrrolizidine alkaloid monocrotaline is a well-documented model of pulmonary hypertension. To our knowledge, however, monocrotaline-induced cardiopulmonary injury has rarely been described and has never been quantitated in mice. In the present study, adult male mice received 2.4, 4.8, or 24.0 mg monocrotaline/kg body weight/day in the drinking water continuously for 6 weeks. These doses represent 1, 2, and 10 times the severely pneumotoxic regimen in rats. Pulmonary endothelial function was monitored by right lung angiotensin converting enzyme (ACE) activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Light and electron microscopy were performed on the left lungs. Cardiac right ventricular hypertrophy was evaluated by the right ventricle to left ventricle plus septum weight ratio (RV/LV + S). Monocrotaline-treated mice exhibited a dose-dependent decrease in lung ACE and PLA activities and an increase in PGI2 and TXA2 production, indicative of endothelial dysfunction. However, these responses were significant only after the highest monocrotaline dose. Light and electron microscopy revealed dose-dependent pulmonary inflammatory and exudative reactions. Unlike previous studies in rats, however, monocrotaline-treated mice developed relatively little lung fibrosis, cardiomegaly, or right ventricular hypertrophy, and no occlusive medial thickening of the pulmonary arteries, even at the highest dose level. These and previous data indicate that there are quantitative biochemical and qualitative morphological differences between mice and rats with respect to monocrotaline pneumotoxicity. Furthermore, in monocrotaline-treated mice (but not in rats) there appears to be a dissociation between lung endothelial dysfunction and inflammation on the one hand, and pulmonary hypertension and fibrosis on the other.

Animals↗
PubMed1989

Structure-function analysis of angiotensin-converting enzyme inhibitors as modifiers of radiation-induced pulmonary endothelial dysfunction in rats.

We have previously demonstrated that thiol-containing collagen antagonists (penicillamine) and angiotensin-converting enzyme (ACE) inhibitors (Captopril and CL242817) ameliorate endothelial dysfunction in irradiated rat lung. The purpose of the present study was to determine whether the non-thiol ACE inhibitor CGS13945 also modifies radiation-induced pulmonary endothelial dysfunction in rats sacrificed 2 months after a single dose (0-30 Gy) of 60 Co gamma rays to the right hemithorax. The CGS13945 was administered in the feed continuously after irradiation at a regimen of 30 mg (kg body weight)-1 day-1. Four markers of lung endothelial function were monitored: ACE activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Right lung ACE and PLA activities decreased with increasing radiation dose, and CGS13945 significantly ameliorated both responses. Dose-reduction factors (DRF) for the inhibitor were 1.80 for ACE activity and 1.41 for PLA activity (p less than 0.05). In contrast, lung PGI2 and TXA2 production increased with increasing radiation dose, and CGS13945 did not influence either response significantly. Thus the ACE inhibitor CGS13945 modifies radiation-induced pulmonary endothelial dysfunction in rats, indicating that the presence of a thiol group is not essential for therapeutic efficacy in this class of compounds. On the other hand, CGS13945 exhibits a differential sparing of radiation-induced pulmonary endothelial dysfunction, as does penicillamine. A structure-function analysis of the present and previous data indicates that all of the ACE inhibitors tested (Captopril, CL242817 and CGS13945) spare the radiation-induced suppression in lung ACE and PLA activity; all of the thiol compounds tested (penicillamine, Captopril and CL242817) spare the radiation-induced elevation in lung PGI2 and TXA2 production; and the thiol ACE inhibitors (Captopril and CL242817) spare all four endothelial responses. These data confirm a novel and potentially important application for ACE inhibitors as modifiers of radiation-induced lung injury, and suggest that there are at least two components to their mechanism of therapeutic action in this model.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Radiation-induced endothelial dysfunction and fibrosis in rat lung: modification by the angiotensin converting enzyme inhibitor CL242817.

The purpose of this study was to evaluate the angiotensin converting enzyme (ACE) inhibitor CL242817 as a modifier of radiation-induced pulmonary endothelial dysfunction and pulmonary fibrosis in rats sacrificed 2 months after a single dose of 60Co gamma rays (0-30 Gy) to the right hemithorax. CL242817 was administered in the feed continuously after irradiation at a regimen of 60 mg/kg/day. Pulmonary endothelial function was monitored by lung ACE activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Pulmonary fibrosis was evaluated by lung hydroxyproline (HP) content. Lung ACE and PLA activities decreased with increasing radiation dose, and cotreatment with CL242817 significantly ameliorated both responses. CL242817 dose-reduction factors (DRF) were 1.3-1.5 for ACE and PLA activity. Lung PGI2 and TXA2 production increased with increasing radiation dose, and CL242817 almost completely prevented both radiation responses. The slope of the radiation dose-response curves in the CL242817-treated rats was essentially zero, precluding calculation of DRF values for PGI2 and TXA2 production. Lung HP content also increased with increasing radiation dose, and CL242817 significantly attenuated this response (DRF = 1.5). These data suggest that the ability of ACE inhibitors to ameliorate radiation-induced pulmonary endothelial dysfunction is not unique to captopril [Ward et al., Int. J. Radiat. Oncol. Biol. Phys. 15, 135-140 (1988)], rather it is a therapeutic action shared by other members of this class of compounds. These data also provide the first evidence that ACE inhibitors exhibit antifibrotic activity in irradiated rat lung.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Radiation-induced pulmonary endothelial dysfunction in rats: modification by an inhibitor of angiotensin converting enzyme.

The ability of the angiotensin converting enzyme (ACE) inhibitor Captopril to modify radiation-induced pulmonary endothelial dysfunction was determined in male rats sacrificed 2 months after a single dose of 10-30 Gy of 60Co gamma rays to the right hemithorax. Half of each dose group consumed feed containing 0.12% w/w Captopril (60 mg/kg/day) continuously after irradiation, and half consumed control feed. Four markers of endothelial function were monitored: ACE activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. All data were plotted as dose-response curves, and subjected to linear regression analysis. The Captopril modifying effect was expressed as the ratio of isoeffective doses at a common intermediate response (DRF), or as the ratio of the response curve slopes. Right lung ACE and PLA activity decreased linearly, and PGI2 and TXA2 production increased linearly with increasing radiation dose. Captopril exhibited DRF values of 1.4-2.1, and slope ratios of 1.4-5.1 for all four functional markers (p less than 0.05). Thus, the ACE inhibitor Captopril ameliorates radiation-induced pulmonary endothelial dysfunction in rats sacrificed 2 months postirradiation. Although the mechanism of Captopril action is not clear at present, these data suggest a novel application for this class of compounds as injury-modifying agents in irradiated lung.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Effect of high salt intake on sodium, potassium-dependent adenosine triphosphatase activity in the erythrocytes of normotensive men.

1. We measured ouabain-insensitive adenosine triphosphatase (ATPase), sodium, potassium-dependent adenosine triphosphatase (Na+,K+-ATPase) and intracellular Na+ and K+ in the erythrocytes of 19 healthy volunteers, before and after supplementation of their normal diet was 6.0-8.9 g of salt (102-137 mmol of NaCl) per day, for 5 days. 2. The subjects had a small but significant gain in weight. Mean plasma renin activity decreased from 1.57 to 0.73 pmol of angiotensin 1 h-1 ml-1 and plasma aldosterone from 0.46 to 0.24 nmol/l. 3. Total ATPase activity fell from 197.9 nmol of inorganic phosphate h-1 mg-1 during the control period to 173.5 during the high-salt period (P less than 0.0125). Na+, K+-ATPase activity fell from 162.2 to 141.4 nmol of inorganic phosphate h-1 mg-1 (P less than 0.05). Intracellular Na+ and intracellular K+ did not change. 4. These results are consistent with the hypothesis that salt-induced volume expansion causes the release of a factor inhibitory to the Na+ pump.

Adult↗
PubMed1988

Coffee consumption and serum cholesterol in the hypertension detection and follow-up program.

The relation between coffee consumption and serum cholesterol level was investigated in a group of 9,043 hypertensive adults who were in the Hypertension Detection and Follow-up Program. In this study, men and women aged 30-69 years at baseline (1973-1974) had their serum cholesterol level measured at the two-year examination (1975-1976). Information about coffee, tea, and cola consumption was also obtained at that time from a food frequency questionnaire. The relation of coffee consumption and serum cholesterol level with potentially confounding variables including age, race, sex, diuretic status, diastolic blood pressure, cigarette smoking, relative weight, physical activity, stress, and education level was examined. When these variables were entered into a multiple regression equation, a positive association with coffee consumption and serum cholesterol level (p less than 0.05) was present. There was no significant relation between serum cholesterol level and consumption of tea, cola, or decaffeinated coffee--the other major contributors of caffeine to the diet--or total caffeine intake. This study indicates a significant positive relation between coffee consumption and serum cholesterol level.

Adult↗
PubMed1988

Split-dose sparing of gamma-ray-induced pulmonary endothelial dysfunction in rats.

The purpose of this study was to determine whether radiation-induced pulmonary endothelial dysfunction exhibits split-dose sparing. Rats were sacrificed 2 months after a range of 60Co gamma-ray doses (0-40 Gy) delivered to the right hemithorax in either a single fraction or in two equal fractions separated by 24 h. Pulmonary angiotensin converting enzyme (ACE) activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production served as indices of lung endothelial function. There were dose-dependent decreases in ACE and PLA activity and increases in PGI2 and TXA2 production after both single and split-dose exposures. The D2-D1 values determined from the two-fraction minus single-fraction isoeffective doses were 3.9 Gy for ACE activity, 7.2 Gy for PLA activity, 4.8 Gy for PGI2 production, and 4.7 Gy for TXA2 production. Thus these data demonstrate that over the present range of radiation doses approximately 4-7 Gy is repairable as subeffective endothelial damage during the 24-h interval between fractions. These values agree with previously published estimates of split-dose sparing in mouse lung based on lethality and breathing rate assays.

Animals↗
PubMed1988

Serum copper concentration as an index of lung injury in rats exposed to hemithorax irradiation.

Serum copper concentration was evaluated as an index of lung injury (monitored by lung prostacyclin production) with respect to the effects of time, dose, dose fractionation, and penicillamine dose modification in rats irradiated to the right hemithorax. Both lung PGI2 production and serum Cu concentration increased with increasing 60Co gamma-ray dose in animals sacrificed 2 or 6 months postirradiation, and the highest values for both responses were observed at the latter autopsy time. At 2 months postirradiation, the elevations in lung PGI2 production and serum Cu concentration also were spared similarly when total radiation doses were delivered in five equal daily fractions as compared to single doses. Finally, the ability of D-penicillamine to ameliorate the radiation-induced hyperproduction of PGI2 by rat lung was accompanied by an attenuation of the dose-dependent increase in serum Cu concentration at 2 months postirradiation in the drug-treated rats. In contrast, serum iron concentration was independent of time, dose, and penicillamine. At 2 months after irradiation, there also was a dose-dependent increase in lung hydroxyproline (collagen) content, the magnitude of which correlated closely with serum copper concentration in individual animals. Thus serum copper concentration is an accurate and minimally invasive index of lung injury in rats irradiated to the hemithorax and can predict lung hydroxyproline (collagen) content in individual irradiated rats.

Animals↗
PubMed1987

Is thiazide-produced uric acid elevation harmful? Analysis of data from the Hypertension Detection and Follow-up Program.

Interaction of thiazide diuretics and the serum uric acid and creatinine levels was studied in 3693 stepped care participants in the Hypertension Detection and Follow-up Program not receiving treatment at baseline. Among men grouped into quartiles by their level of uric acid at baseline, the upper quartile (average uric acid, 7.7 mg/dL [458 mumol/L]) had an average serum creatinine level of 1.2 mg/dL (106 mumol/L) and the lowest quartile (uric acid, 4.9 mg/dL [291 mumol/L]) had an average serum creatinine level of 1.1 mg/dL (97 mumol/L). Similar findings were present in women. Therapy with chlorthalidone or other thiazide-type diuretics tended to increase levels of uric acid and creatinine, but the increase in both was less in the upper quartile than in the lower quartile. Among individuals who were prescribed uric acid-lowering drugs, the level of serum creatinine increased just as much as in those whose uric acid level was not pharmacologically lowered. Baseline uric acid level was a weak predictor of mortality in men; the introduction of an interaction term for creatinine suggested that this effect was primarily restricted to those with elevated levels of both uric acid and creatinine at baseline. Change in uric acid level at one year after therapy was inversely correlated with mortality in men. There were few episodes of gout (only 15 recorded in five years among 3693 participants at risk). These results suggest that neither the baseline uric acid level nor the change in uric acid level produced by therapy injures the kidney. These results suggest no reason to lower uric acid levels pharmacologically in the treated hypertensive patient who is not gouty. They leave unanswered whether there is a predictive value to baseline uric acid level not explainable by other correlated cardiovascular risk factors.

Adult↗
PubMed1987

Brain surface exposure to CO2 and NdYag laser application: effect on pulmonary endothelium response in the rat.

Pulmonary endothelial cells and the renin-angiotensin-aldosterone (RAA) system respond to different types of injury (direct or indirect) with variations in their functions. These variations influence the regulatory mechanisms of pulmonary and systemic blood pressure, electrolyte balance and fibrinolysis. Concentration changes of some components of the RAA system and lung plasminogen activator were observed following NdYag laser application to the brain surface in rats. These changes were similar to those observed in cutaneous burn and haemorrhagic hypotension. CO2 laser application did not cause the same changes.

Aluminum Silicates↗
PubMed1987

Functional responses of the pulmonary endothelium to thoracic irradiation in rats: differential modification by D-penicillamine.

Male rats were sacrificed 2 or 6 months after a range of single doses of gamma rays (0-30 Gy) to the right hemithorax. Half of each dose group consumed control feed continuously after irradiation, and half consumed feed containing the collagen antagonist D-penicillamine (10 mg/rat/day). Four markers of pulmonary endothelial function were monitored: angiotensin converting enzyme (ACE) activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Bronchoalveolar lavage (BAL) fluid also was obtained from the right lung, and was analyzed for macrophage number, and PGI2 and TXA2 concentration. Right lung ACE and PLA activities decreased linearly with increasing dose at both 2 and 6 months postirradiation, and penicillamine had no significant effect on either response. In contrast, PGI2 and TXA2 production by the right lung increased linearly with increasing radiation dose at both autopsy times. Penicillamine significantly ameliorated the increase in PGI2 production at 2 months, and the increase in TXA2 production at both 2 and 6 months postirradiation. Penicillamine dose-reduction factors (DRF) for PGI2 and TXA2 production were 1.3-1.4, and the response curve slope ratios were 1.7-2.5 (p less than 0.05). Penicillamine also ameliorated the dose-dependent increase in TXA2 concentration in the BAL fluid at 2 months. These data indicate that the four "markers" of radiation-induced pulmonary endothelial dysfunction do not respond identically to penicillamine dose-modification. Of the four markers, TXA2 production exhibits the most significant and widespread penicillamine sparing. TXA2 is a potent vasoconstrictor, promoter of platelet aggregation, and mediator of inflammation, and partial prevention of the radiation-induced hyperproduction of this eicosanoid may account in part for penicillamine's therapeutic action in this model.

Animals↗