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Biomedical subjects

M Saric

Publications and source records attributed to M Saric.

18 recordsLinked to original sources
PubMed2000

Unusual eustachian valve function.

The eustachian valve directs oxygen-rich blood from the inferior vena cava toward the foramen ovale and away from the tricuspid valve during fetal development. Ordinarily, it does not prevent reflux of right atrial blood back into the inferior vena cava because it does not function as a true valve. Here we describe an unusual adult patient with severe tricuspid valve regurgitation in whom the eustachian valve did function as a true, albeit regurgitant, valve.

Aged↗
PubMed2000

Effect of a bis-benzyl polyamine analogue on Pneumocystis carinii.

Pneumocystis carinii is the causative agent of P. carinii pneumonia (PCP), an opportunistic infection associated with AIDS and other immunosuppressed conditions. Although polyamine metabolism of this fungus has been shown to be a chemotherapeutic target, this metabolism has not been thoroughly investigated. Reported here is the effect of one polyamine analogue, N, N'-bis[3-[(phenylmethyl)amino]propyl]-1,7-diaminoheptane (BBS), on P. carinii. BBS inhibits the growth of P. carinii in culture, but at concentrations higher than those required to inhibit the growth of other pathogens. However, BBS is at least as active in an animal model of PCP as in other models of diseases studied. BBS causes some reduction in P. carinii polyamine content and polyamine biosynthetic enzyme activities, but the effect is less than that observed with other pathogens and very much less than the effect of the polyamine biosynthesis inhibitor DL-alpha-difluoromethylornithine. BBS enters P. carinii cells via a polyamine transporter, unlike all other cells that have been studied. P. carinii cells do not remove the benzyl groups of BBS, as is reported for mammalian cells. The most likely mode of action is displacement of natural polyamines. Overall, the activity of BBS provides further evidence that polyamines and polyamine metabolism are rational targets for the development of drugs to treat PCP. Because the details of BBS-P. carinii interaction differ from those of other cells studied, polyamine analogues may provide a highly specific treatment for PCP.

AIDS-Related Opportunistic Infections↗
PubMed1997

Fibrosis in the subacromial bursa and outcome after acromioplasty.

BACKGROUND AND AIMS: The subacromial bursa tends to undergo proliferative or degenerative changes in patients with impingement syndrome. The aim of the study was to quantify the degree of fibrosis in the subacromial bursa in context with the outcome after acromioplasty. MATERIAL AND METHODS: Twenty-one patients with impingement syndrome underwent acromioplasty, and in each case biopsies from the subacromial bursa were taken. Fibrosis in the subacromial bursa was assessed histologically with van Gieson staining technique, and a three-graded scale was used. Five normal shoulders from an autopsy series served as controls. RESULTS AND CONCLUSIONS: Ten patients had severe fibrosis, eight had moderate fibrosis and one patient had no fibrosis at all. All normal controls had no fibrosis. The postoperative outcome seemed to be more favourable in patients with severe fibrosis (7 out of 10) contrary to patients with moderate fibrosis of whom only three out of eight were graded as a success. The outcome of acromioplasty in patients with impingement was clearly dependent on the degree of fibrosis in the subacromial bursa.

Acromioclavicular Joint↗
PubMed1994

Combination chemotherapy of drug-resistant Trypanosoma brucei rhodesiense infections in mice using DL-alpha-difluoromethylornithine and standard trypanocides.

Combinations of DL-alpha-difluoromethylornithine (DFMO; eflornithine; Ornidyl) with either suramin or melarsen oxide were found to be effective against acute laboratory model infections with Trypanosoma brucei rhodesiense. We used clinical isolates known to be resistant to these drugs when used singly. An infection with a melarsen oxide-refractory isolate was cured by a combination of low-dose DFMO (0.5% in the drinking water) plus low-dose suramin (1 mg/kg of body weight given intraperitoneally). Another strain, moderately resistant to arsenical drugs, was cured with combinations of 4% DFMO with 5 mg of melarsen oxide per kg. Furthermore, a combination of DFMO (2% in the drinking water) and suramin (20 mg/kg) provided a 100% cure rate in a central nervous system model, although the same doses of these drugs used singly were completely ineffective. The synergism of DFMO and suramin against an acute infection was improved when suramin was given at the end of the DFMO administration. No adverse interactions were observed when high doses of DFMO combined with high doses of suramin were administered to uninfected mice. These results suggest that combinations of DFMO and suramin should be examined clinically for activity in arsenical-drug-refractory cases of East African sleeping sickness.

Animals↗
PubMed1993

N-n-alkyl-3,4-dihydroxybenzamides as inhibitors of the trypanosome alternative oxidase: activity in vitro and in vivo.

On the basis of our previous demonstration of the high inhibitory activity of a series of p-n-alkyloxybenzhydroxamic acids and n-alkyl esters of 3,4-dihydroxybenzoic acid against the trypanosome alternative oxidase in a cell-free mitochondrial preparation of Trypanosoma brucei brucei, we synthesized a series of N-n-alkyl-3,4-dihydroxybenzamides for evaluation as inhibitors of this enzyme. This class of compounds was selected with the expectation of their having similar inhibitory activity to but greater solubility than the esters and hydroxamic acids noted above and greater resistance to serum hydrolases in vivo. We predicted that such properties would allow an inhibitor of the trypanosome alternative oxidase to be coadministered with glycerol as a means of providing treatment for infections by African trypanosomes. As expected, such benzamides were both more soluble and more stable, some being more active against the target enzyme than the corresponding ester. One, N-n-butyl-3,4-dihydroxybenzamide, was selected for evaluation in vivo against T. brucei brucei. When combined with glycerol, this benzamide was found to be curative. A regimen wherein 450 mg of N-n-butyl-3,4-dihydroxybenzamide per kg and 15 g of glycerol per kg were given hourly in three divided doses cured 17 of 19 mice with established T. brucei brucei infections. This combination is more active in vivo than any other designed to block simultaneously both the unique respiratory electron transport system and the anaerobic glycolytic pathways of these pathogenic protozoa.

Animals↗
PubMed1993

The once and future health system in the former Yugoslavia: myths and realities.

This paper debunks three widely believed myths about the former Yugoslavia's health care system: that it was characterized by: (1) social ownership of "self-managing" provider organizations; (2) a commitment to primary health care; and (3) a faith in what might be called the "march of progress"--the health system's continuous expansion and improvement. In contrast to this picture, we present an alternative view and conclude with a word of caution for American consultants and health care reformers in Eastern European countries and newly independent states: If universal health coverage is to be maintained, beware of reforms that do no more than substitute private for public organizational forms.

Civil Disorders↗
PubMed1991

Mitochondrial development in Trypanosoma brucei brucei transitional bloodstream forms.

Intermediate and short stumpy bloodstream forms of Trypanosoma brucei brucei are transitional stages in the differentiation of mammal-infective long slender bloodstream forms into the procyclic forms found in the midgut of the tsetse vector. Although the mitochondria of the proliferative long slender forms do not accumulate rhodamine 123, the mitochondria of the transitional forms attain this ability thus revealing the development of an electromotive force (EMF) across the inner mitochondrial membrane. The EMF is inhibited by 2,4-dinitrophenol, rotenone and salicylhydroxamic acid but not by antimycin A or cyanide. Consequently, NADH dehydrogenase, site I of oxidative phosphorylation, is the source of the EMF and the plant-like trypanosome alternative oxidase (TAO) supports the electron flow serving as the terminal oxidase of the chain. Although the TAO is present in the long slender forms as well, it serves only as the terminal oxidase for electrons from glycerol-3-phosphate dehydrogenase. The data presented here, combined with older data, lead to the conclusion that the mitochondria of transitional intermediate and short stumpy forms likely produce ATP. This putative production is either by F1F0 ATPase driven by the complex I proton pump or by mitochondrial substrate level phosphorylation, or most likely by both. These conclusions contrast with the previously held dogma that all bloodstream form mitochondria are incapable of ATP production.

2,4-Dinitrophenol↗
PubMed1991

Early detection of interstitial lung disease in asbestos exposed non-smoking workers by mid-expiratory flow rate and high resolution computed tomography.

Ten years of lung function and radiological findings in six non-smoking asbestos exposed subjects who had increased mid-expiratory flow rate (FEF 25-75%) as the only functional abnormality were prospectively analysed. A biphasic change in FEF25-75% was noted. It initially increased up to the fifth year, and then a decrease was seen. In the final three years of the study, FEF25-75% reduction correlated well with a decrease in pulmonary capacity for CO (DLCO). During that time high resolution computed tomography (HRCT) probability scores correlated inversely with FEF25-75% and with DLCO, whereas chest radiography was unchanged (International Labour Organisation (ILO) profusion below 1/1). For five of the six subjects HRCT probability of asbestosis was intermediate. An increase in FEF25-75% in some asbestos exposed non-smoking workers may be one of the earliest functional signs indicative of future development of parenchymal asbestosis. Early asbestos related parenchymal abnormalities are seen more frequently on HRCT than on chest radiography.

Adult↗
PubMed1990

Differential susceptibility to DL-alpha-difluoromethylornithine in clinical isolates of Trypanosoma brucei rhodesiense.

DL-alpha-Difluoromethylornithine is an enzyme-activated inhibitor of ornithine decarboxylase and an antagonist of polyamine metabolism that has been successful in clinical trials against West African sleeping sickness caused by Trypanosoma brucei gambiense. Its potential for use against the more virulent East African form of the disease, caused by T. brucei rhodesiense, is not certain. We examined 14 East African clinical isolates from the Kenya Trypanosomiasis Research Institute strain bank plus 2 established isolates for susceptibility to DL-alpha-difluoromethylornithine and to standard trypanocides. Seven of 16 strains were partially or totally refractory to DL-alpha-difluoromethylornithine in our test system. Four strains were also refractory to arsenical drugs, and five were refractory to diamidines. The results indicate that other novel agents or combinations of established agents may be needed for chemotherapy of East African disease.

Animals↗
PubMed1979

Airway responsiveness in workers processing polyester resins.

In 22 employees of a button-manufacturing plant, exposure to polyester resins over an eight-hour work shift resulted in an acute reduction of flow rates on maximum expiratory flow volume (MEFV) curves at MEF50% and MEF25%. In the workers studied, preshift administration of 80 mg of propranolol potentiated, while 1 mg of subcutaneously injected atropine significantly inhibited, the bronchoconstricting effect of the resins, indicating that the autonomic nervous system plays an important role in determining airway smooth muscle response to polyester resins. Although a high prevalence of acute symptoms (cough, shortness of breath, throat and eye irritation) over the work shift was recorded in exposed workers, no high prevalence of chronic respiratory symptoms was found. No definite evidence of chronic airway obstruction was recorded in exposed workers.

Adult↗
PubMed1976

Follow-up of ventilatory lung function in a group of cement workers.

In a group of 160 active cement workers and 80 control workers selected on the basis of having or not having symptoms of chronic bronchitis, forced vital capacity (FVC) and one second expiratory volume (FEV 1-0), both corrected for age and height, and ratio of one second forced expiratory volume to forced vital capacity (FEV 1-0/FVC (%)) were measured on two occasions with an interval of four and eight years respectively.

Adult↗
PubMed1976

Malignant tumors of the liver and lungs in an area with a PVC industry.

The incidence of malignant tumors of the lung and bronchus and of cytologically confirmed primary malignant tumor of the liver was analyzed for a 4-yr period in a city with several factories, including a PVC industry. Prior to the study two cases of angio-sarcoma of the liver were diagnosed in workers employed in PVC production. The total incidence of analyzed tumors was only slightly higher than predicted. The tumors of the liver recorded did not show any dependence on place of work or residence. During the period of observation, malignant tumors of the bronchus (lung) were not recorded in the PVC industry. Their rate in the area in which the PVC industry is situated was approximately the same as that for the entire city area. The study does not indicate that the occurrence of malignant tumors other than angiosarcoma is associated with exposure to vinyl chloride.

Adult↗
PubMedDate not supplied

Occupational and environmental exposures and nonspecific lung disease--a review of selected studies.

Selected studies show that nonspecific lung diseases are a major occupational and environmental health hazard. Exposure to mineral dusts (such as cement and brown coal) and organic dusts (cotton, hemp and flour) as well as manganese and gaseous irritants causes significant upper respiratory tract injury. Possible additive effects of mixed exposures, combined exposure to dusts and gaseous irritants of the upper respiratory tract, individual susceptibility, and mechanisms of nonspecific respiratory effects of exposures are considered. Interpretation of the results is difficult due to uncontrolled confounding. Measures for preventing lung impairments include exposure reduction and preemployment examination of workers.

Animals↗