The lung surfactant system (LSS) has a complex morphological and biochemical structure. LSS contains two components: cellular and non-cellular. The cellular component comprises three types of alveolar epithelium cells (type I, II, and II pneumocytes), alveolar macrophages (AM) and Clara bronchiolar cells. The non-cellular component consists of alveolar surfactant (AS), hypo(epi)phase and alveolar epithelium cell glycocalix. AS represents phospholipids, proteins and carbohydrates mono-molecular layer. AM lamellar bodies (LB) and tubular myelin (TM) are disposed in the hypophase. LB and TM represent the depot-forms of lung surfactant (LS). Lung surfactant (LS) has a complex biochemical structure and comprise the following components: phospholipids, neutral lipids, glycolipids, surfactant-specific proteins, plasmaproteins, enzymes, carbohydrates and aminoacids. LS is synthesized in type II pneumocytes and Clara cells. LS catabolism is mainly effected by AM. The LSS has a fundamental role in the physiological functions of lungs. Through its antiatelectatic and antioedematic functions, LSS sustains the basic physiological functions of lungs--alveolar ventilation and gas diffusion through the alveolar-capillary wall. Besides this, LSS performs several protecting functions--antioxidant defense, non-specific defense mechanisms, immunodulatory action, cytotoxicity agents metabolism and others. The injury of the structure and functions of LSS is an important pathogenic mechanism in the pathogenesis of different lung diseases. Practically, a pathological process in lungs, which is not related to changes in LSS structure and functions, does not exist. Recently developed surfactant replacement therapy with natural and synthetic surfactants has an important place in the therapy of several lung diseases.
The longitudinal study encloses 53 patients with PSS followed up for a period of 6 years. The most frequent changes in the parameters of pulmonary function are: diffusing capacity impairment--reduction in DICO (86.8% of the patients), restrictive lung disease pattern (50.9% of the patients) and arterial hypoxemia (43.4% of the patients). The duration of PSS and the follow up period do not cause significant changes in the pulmonary function parameters and the arterial blood-gas analysis in the group of patients studied.
An analytical review was made on the pathophysiological mechanisms suspected to be involved in dyspnea, accepting that the sensation of shortness of breathing, and the subjective signs (exertion, anxiety and fear) are essential for the diagnosis of this condition. Bearing in mind the anatomical relations in the central nervous system between the structures involved in the control and regulation of the respiration, and these involved in the emotions, a scheme was presented of the pathophysiological mechanisms, which determine the essential signs of the dyspnea. Three neuronal circuits were assumed for the explanation of the manifestations in dyspnea: subjective signs, symptoms of the thoraco-pulmonary and cardio-vascular systems, and these of the voluntary muscular system that accompanied dyspnea.
The chronic hypoxemia seems to play an important role in the pathogenesis of hemodynamic disorders in chronic obstructive pulmonary disease (COPD). The aim of the study was to follow-up the changes in pulmonary hemodynamics in COPD with mild respiratory failure. 78 COPD patients with Ist and IId degree of respiratory failure were investigated. The following investigations were carried out: two--dimensional echocardiography, spirometry, arterial blood gases and acid-base balance. In 18 of COPD patients a right heart catheterization was performed and the following indices were determined: mean pulmonary arterial (PA) pressure, pulmo-capillary resistance, teledyastolic right ventricular volume. The echocardiography showed significantly higher mean PA pressure values, an initial right ventricular dilatation and right ventricular wall hypertrophy. The indices of right heart catheterization were changed, too. The pulmo-capillary resistance was significantly increased. It was the most sensitive early parameter. The mean PA pressure was increased. There was no significant difference between the mean PA pressure determined by echocardiography and by right ventricular catheterization. A relationship between the degree of hypoxemia and the hemodynamic changes was found. The long development of COPD with mild respiratory failure leads to disorders in lung microcirculation and early changes in pulmonary hemodynamics. This process worsens the prognosis of COPD and the early prevention in the complex therapy of the disease is necessary.
Views and experimental data on the role of interleukins in the regulation of the endocrine functions of hypothalamus, pituitary gland, thyroid gland, suprarenal gland and pancreas are presented. The role of interleukin-1 and interleukin-6 in the regulation of normal and pathological processes is examined. Data on cellular and molecular operation mechanisms of some interleukins on functions of the endocrine glands are included in the survey. The clarification of these mechanisms leads to new pharmacotherapeutical approaches to endocrine diseases treatment.
Patients with metabolic syndrome show augmented cardio-vascular risk, at least in part mediated through disequilibrium between mechanisms generating free radicals, and antioxidant defense. Carbohydrate and lipid disturbances in metabolic syndrome induce oxidative stress via several non fully understood mechanisms. Glucose overload in oral glucose tolerance test (OGTT) can also induce oxidative stress. The aim of our study was to evaluate changes in superoxide dismutase and glutathione peroxidase activity, as well as total antioxidant status in OGTT in patients with metabolic syndrome and in healthy subjects. OGTT was performed in 36 healthy volunteers and in patients with metabolic syndrome. Glucose, Insulin, and triglycerides were evaluated at 0th, 30th, 60th, 120th, and 180th min. Superoxide dismutase and glutathione peroxidase were measured at 0th, 60th, and 120th min. Total antioxidant status was measured at 0th, and 120th min. At 0th min total, HDL and LDL cholesterol were evaluated. A statistically significant decrease (p < 0.05) in superoxide dismutase activity at 120th as compared with 60th min were observed. Glutathione peroxidase activity decreased significantly (p < 0.05) even though at 60th as compared with 0th min and remained decreased at 120th min. Total antioxidant status was found to be increased (p < 0.05) at 120th as compared with 0th min. The observed dynamic in patients did not differed (p > 0.05) from control group. The study shows a decrease in antioxidant enzyme activity and a compensatory increase in total antioxidant status, indicating a surcharge of antioxidant homeostasis. In context of carbohydrate and lipid disturbances in metabolic syndrome, this is to suggest an existing of complementary pathogenic mechanisms, able to aggravate cardiovascular risk in these patients. Correction of metabolic disturbances may be an efficacious tool for influencing on prooxidant-antioxidant homeostasis too.
In the present experiment, we have investigated the impact of the acute copper deficiency on the pathogenesis of stress ulcers' formation in rats during cold-restraint stress. A powdered milk diet, lasting for 5 days, causes a significantly decrease of stomach copper content in rat, comparing to content in rats receiving standard laboratory diet. The severity of mucosal disturbances, expressed as total number and area of stress ulcers, is most prominent in animals receiving hypocupric diet. Their treatment with Ranitidine extends the morphological disturbances in the stomach mucosa and produces highest level of lipid peroxidation and lowest activity of superoxide dismutase in the stomach compared to the other groups. In conclusion, the appropriate copper balance plays an essential role for the natural resistance of the stomach mucosa and Ranitidine, in conditions of acute copper deficiency, makes deeper the disturbances produced by stress.
Adult respiratory distress syndrome (ARDS) is not a specific lung disease. It represents an acute respiratory insufficiency syndrome in patients with non-injured lung as a result of severe multiple lung lesions of different etiology and pathogenesis. ARDS is provoked by a great number of etiologic factors of two main groups: 1) etiologic factors directly injuring the alveolo-capillary wall and 2) etiologic factors indirectly injuring the alveolo-capillary wall. ARDS develops in three phases: phase of exudation, phase of injury of the alveolocapillary wall and phase of proliferation (chronic phase).
Objective of the study is to investigate the hypotheses regarding the correlation of serum levels and urinary excretion of electrolytes with arterial hypertension. 211 subjects aged 50-54 from Bulgarian Army were studied. Evaluated were following parameters: SBP, DBP, BMI, Na+, K+ in blood serum; Na+, K+, NaCl, KCL, Na/K ratio, Ca++, Mg++ in 24-h urine excretion. Statistical analysis of variance, dispersion and correlation analysis (using 6D program from statistical pack BMDP) were applied. In the blood, no correlation was found between Na+ and both SBP and DBP. A significant positive correlation between SBP and K+ was found only in non-obese hypertensive females (R = 0.59, p < 0.05). Correlation between K+ and DBP was negative in separate groups with normal BMI (R = -0.84, R = -0.65, p < 0.05). In the 24-h urine excretion, no correlation was found between K+, NaCl, KCL and SBP, as well as between Na+ and SBP and DBP. Significant positive correlation was found between K+ and DBP in obese hypertensive subjects (R = 0.56, p < 0.05) and between NaCl and DBP (R = 0.47 up to R = 0.66 in separate groups, p < 0.05). Significant positive correlation between Ca++ and DBR (R = 0.47) was found in obese hypertensives. Mg++ correlates positively with DBP (R = 0.62 in some groups). Urine levels of Ca++ and Mg++ were significantly higher in normatensives. Electrolytes in blood and urine were closely related to DPB rather than to SBP. K+ levels in blood affect only DBP. Our data do not confirm the hypothesis for the positive correlation between urinary Na(+)-excretion and BP (except in obese subjects). The hypothesis about the inverse relation of K(+)-intake to BP, especially to DBP is confirmed by our data. The data regarding the Ca++ and Mg++ urinary excretion and their correlation with DBP and SBP are very discordant and do not give an opportunity to make definite conclusions. Our data confirmed the hypothesis about the natriuretic effect of Mg++, which possibly is of a protective value for development of AH in some obese persons.
In a previous paper (Balanova, Surcheva and Ichev, 2001) we have proposed a scheme about pathophysiological mechanisms involved in dyspnea. Some of the clinical problems in dyspnea were discussed in this paper on the base of that scheme, as well as clinical observations on the patients with dyspnea. Two groups of symptoms were considered--subjective and objective, and their significance for the diagnosis of the dyspnea and of the disease that provokes dyspnea were evaluated. A critical analysis of the different forms of dyspnea has been made, and suggestions about the treatment of the subjective symptoms in dyspnea were proposed.
The congestive heart failure (CHF) has become one of the most common syndromes afflicting the population. The long-term prognosis of these patients is bad. The CHF shows a tendency toward fast progressive development. The aim of our study was a retrospective investigation on CHF patients, a determination of CHF functional class by NYHA and its type, a determination of the most important diseases leading to heart decompensation and of the reasons for dead in these patients. For a 6-year period we investigated 6428 patients. 1095 (17.03%) of them were with a different degree of CFH. More of them were with II and III functional class of CHF by NYHA. In the age decade from 61 to 70 years the frequency of CHF increased significantly. The most important diseases leading to CHF syndrome were chronic ischemic disease, arterial hypertension, COPD with chronic cor pulmonale and valve diseases. The average age of deceased CHF patients was 67.8 +/- 7.4 years. After the manifestation of the first group of symptoms the mean life duration of CHF patients was 13.2 +/- 4.1 years.
In this research there were studied the changes in the concentrations of pyruvate, lactic acid, maleate, beta-oxybutyric acid oxyacetyc acid, blood fats, triglycerides, cholesterol blood lipoproteins in patients in different stages of compensation of diabetes mellitus. Studied were 44 patients during ablatio retinae during latentive diabetes, 16 patients with decompensated, 12 with subcompensated, and 8 with compensated diabetes. The average age of the studied patients was 54 years. The control group of 35 healthy people was of average age 52 years. All the groups show decreasing of the blood maleat. In the group of decompensated diabetes decreasing of keto-bodies, piruvat acid and lipid fractions was present. These factors were normalized, when diabetes was compensated. In this study, the diagnostic value of the investigation metabolites for compensation of diabetes mellitus is discussed.
Prostate-specific antigen (PSA) is a serine protease with chymotrypsin-like enzymatic activity. In males PSA is produced by the prostatic gland and it is present in prostatic tissue, seminal plasma and male serum. Initially, PSA was believed to be absent from all female tissues and fluids. However PSA has been detected recently in some female tissues (including breast, ovarian and endometrial tissues) and body fluids (serum, milk, amniotic fluid). The presence of PSA in these female tissues seems to be closely associated with steroid hormone regulation, especially androgens and progestins. Estrogen by itself seems to have no effect on PSA regulation, but it can impair androgen induced PSA production. In the tissues and fluids examined PSA is found in two molecular forms: free PSA is the enzymatically active form and in a complexed form bound to protease inhibitors. The data presented suggest that PSA can no longer be regarded as a specific prostatic marker, but as a protein that could be produced by cells bearing steroid hormone receptors under conditions of steroid hormone stimulation. Its biological role is not fully clarified, but PSA may be a candidate growth factor in normal tissues, pregnancy and tumors. At this point, PSA shows promise of being routinely used as a favorable prognostic indicator in female breast cancer.
Members of macrolides are Erythromycin, Oleandomycin, Spiramycin, Roxithromycin, Josamycin, Midecamycin, Clarithromycin, Azithromycin and Dirithromycin. This review present mechanism of action, pharmacokinetic, adverse drug reactions and main clinical uses of the macrolides.
Adult respiratory distress syndrome (ARDS) represents an excessively dangerous acute respiratory failure, as result of diffuse damage of alveolocapillary membranes in stiff noncompliant lungs. ARDS is a widely disseminated syndrome caused by severe etiologic factors. ARDS usually appears within 12 to 72 hours of an identifiable clinical event and progresses through three phases: 1. exudative phase; 2. alveolar membrane damage and pulmonary surfactant systems; and 3. proliferative phase. Nearly all of the deaths occur within 30 days of the onset of the syndrome. The mortality rate varies according to the causes and the age. ARDS progresses through three clinical phases: 1. basis respiratory failure; 2. progressive respiratory failure; and 3. total respiratory failure. The therapy of ARDS is complex. It consists of: 1. background general therapy of ARDS; 2. background supportive therapy of ARDS; 3. definitive therapy to interrupt mechanisms of inflammation and pulmonary injury; 4. new pharmacologic supportive therapy.
Ceftibuten is an orally active third generation new cephalosporin. Its antibacterial activity in vitro was tested to many clinical isolates and was compared to the activity of ceftazidime, cefuroxime and ampicillin, by twofold serial dilution method in Müller-Hinton agar--detection of minimum inhibitory concentrations (MIC) and by the disc-diffusion method of Kirby-Bauer. The new cephalosporin demonstrated great activity against the different clinical important strains. Many resistant strains to ampicillin were high susceptible to ceftibuten. The majority of Gram-negative organisms, including Enterobacteriaceae, the respiratory pathogens M.(B.) catarrhalis and H. influenzae are highly susceptible to Ceftibuten, however Pseudomonas, Acinetobacter are resistant. The majority of methicillin-susceptible strains of Staphylococcus are resistant too. New cephallosporin was also active against S. pyogenes (Streptococcus gr. A) and penicillin-susceptible pneumococci, but was inactive against S. agalactiae (Streptococcus gr. B), S. pneumoniae penicillin-resistant strains and enterococci, similar to the other cephalosporins. The activity of ceftibuten was higher than that of ampicillin and cefuroxime against beta-lactamases positive strains of H. influenzae and M.(B) catarrhalis, also against tested strains of Enterobacteriaceae. The major priority of the new antibacterial agent over other cephalosporins and ampicillin is its stability to hydrolysis by the main broad-spectrum beta-lactamases producing E. coli and K. pneumoniae sp.
Organism's good tolerance toward Ranitidin and Famotidin makes possible an application of doses higher than the ones put into everyday practice. This is a very favorable circumstance considering the fact that according to some authors the decreasing of acidity in oesophagus apparently depends on the applied dose of the medicine. Thus the treatment with famotidin 2 x 40 mg allows an additional decreasing of acidity in lower oesophagus. We investigate the effect of intravenous application of famotidin (quamatel) in dose 2 x 20 mg and 2 x 40 mg as monotherapy in cases of reflux-oesophagitis and erosive gastritis as well as organism's tolerance toward it. There are 23 patients studied--17 men and 6 women, between 18 and 70 years old. The diagnoses are: reflux-oesophagitis--23, chronic erosive gastritis and reflux-oesophagitis--8. The patients are selected according to clinical criteria--scalding and/or pain in the oesophagus accompanied with acidity in the mouth cavity. The diagnoses are put gastoscopically. The results of the intravenous applying of quamatel are accounted in reference to the clinical complaints (scalding and/or pain in the oesophagus, acidity in mouth cavity) as well as to the endoscopic and histologic changes in the oesophagus and stomach mucosa. In patients with chronic erosive oesophagitis the efficiency of treatment was confirmed with complete epithelization of the erosions in 22 of 23. The short-period use of large doses 2 x 40 mg quickly improves the clinic symptoms and decreases the period of epithelization twice. The clinic experience shows that the intravenous form of quamatel remains the most effective in cases of short-term and intensive therapy of erosive gastritis with accomplicated hard and emergency clinical cases when the aim is to be avoided the peroral application of anti-ulcer means. An important advantage of the intravenous treatment with quamatel is its low price.
The andropause (andropaenia) or PADAM-syndrome represents a combination of clinical and laboratory symptoms, developed during aging. The most frequently reported clinical feature is erectile dysfunction. From the laboratory parameters the most typical finding is low normal or reduced serum testosterone levels. Very useful questionnaires have been developed helping in diagnosing the PADAM syndrome. Nowadays the hormonal replacement therapy with testosterone derivatives is considered to be the "gold standard". It has positive impact on the cardiovascular risk profile and its different components. This therapy is being prescribed on clear indications and according to strict rules. Available preparations in our country are the injectable and oral ones. Replacement therapy with other hormones is still not a part of clinical practice.
The knowledge that an oxidizing of LDL is necessary for the foam cell formation is in the basis of the so called oxidative hypothesis of atherosclerosis. The role of LDL-oxidation for the atherosclerotic plaque formation, as well as its association with inflammatory processes in the vascular wall, are well established. The important conclusion of this hypothesis is the possible role of the antioxidants attenuating atherosclerotic mechanisms. The advances in studying the principal antioxidant vitamins E, C and beta-carotene effects, revealed a great part of their molecular mechanisms, which are not necessarily antioxidative. The important aspects of the cooperative antioxidant action are revealed too, including the so called tocopherol-mediated peroxidation, suggesting the need of the co-antioxidants for effective antioxidant defense. In the recent years many vitamin antioxidant supplementations are used. The epidemiological results of such supplementation do not always reveal the same beneficial effects as expected theoretically or based on the observations made with diet rich in fruits and vegetables. The present paper generalizes the thought concerning the impact of oxidized LDL in atherosclerosis, as well as mechanisms of action and pharmacokinetics of the most widely used antioxidant vitamins--E, C and beta-carotene, and the perspectives of their usage in cardio-vascular prophylaxy based upon the recent experience in antioxidant vitamin supplementation.
The faith that an oxidizing of LDL is necessary for he foam cell formation is basically for the so called oxidative hypothesis of atherosclerosis. The role of LDL-oxidation for the atherosclerotic plaque formation, as well as its association with inflammatory processes in the vascular wall, are well established. The important conclusion of this hypothesis is the possible role of the antioxidants attenuating atherosclerotic mechanisms. The advances in studying the principal antioxidant vitamins E, C and beta-carotene effects, revealed a great part of their molecular mechanisms, which are not necessarily antioxidative. The important aspects of the cooperative antioxidant action are revealed too, including the so called tocopherol-mediated peroxidation, suggesting the need for the co-antioxidants for effective antioxidant defense. In the recent years many vitamin antioxidant supplementations are used. The epidemiological results of such supplementation do not always reveal the same beneficial effects as expected theoretically or based on the observations made with a diet rich in fruits and vegetables. The present paper generalizes the thought concerning the impact of oxidized LDL in atherosclerosis, as well as mechanisms of action and pharmacokinetiks of the most widely used antioxidant vitamins--E, C and beta-carotene, and the perspectives of their usage in cardiovascular prophylaxy bazed upon the recent experience in antioxidant vitamin supplementation.
