Great scientific discoveries rarely originate from small and poor countries. However, the lives and achievements of three Yugoslav scientists who were active in the biomedical sciences, Laza K. Lazarević (1851-1891), Ivan Djaja (1884-1957), and Pavao Stern (1913-1976), serve as an example of success in this environment. These scientists, as well as the majority of other successful investigators in small and poor countries, were trained in foreign and developed countries and, upon return, were given the freedom to start a selfdependent research program. They overcame many obstacles, including wars and civil unrests, to contribute significantly to certain medical fields. It is interesting that although a Jew, Stern was allowed to work during the World War II in Zagreb, which became capital of the so-called Independent State of Croatia, a puppet state under German control. Perhaps his good name among pharmacologists helped him to keep position during this tough period. Nowadays, new technologies requiring for biomedical research are rather expensive, and poor countries cannot afford to finance many scientists. Thus, selection of the most productive researchers is the challenge for those who finance scientific work.

Using spectrophotometric assay, we have studied the distribution of α-D-mannosidase, β-D-galactosidase, and N-acetyl-β-D-glucosaminidase in hog serum, the aqueous humor, optic nerve, retina, and uvea (iris, ciliary body, choroid). N-acetyl-β-D-glucosaminidase was the most active gycosidase in all tissues that we studied. The highest activity of α-D-mannosidase was found in the extracts prepared from the iris, while β-D-galactosidase and N-acetyl-β-D-glucosaminidase were the most active in the extracts of the choroid and ciliary body, respectively. The aqueous humor and serum had several times lower specific activity of glycosidases than did the extracts of ocular tissues or optic nerve. There was no significant difference between the activity of these enzymes in the aqueous humor and serum. High activity of glycosidases in the optic nerve suggests their role for intrinsic axonal repair. Retinal extracts had the smallest glycosidase activity of all ocular extracts prepared. The physiological role of these findings is discussed.

This review summarizes some basic properties and distribution of angiotensin I converting enzyme (ACE). ACE is one of several biologically important ectoproteins that exists in both membrane-bound and soluble forms. Localized on the surface of various cells, ACE is inserted at the cell membrane via its carboxyl terminus. Human plasma ACE originates from endothelial cells while other body fluids may contain ACE that originates from epithelial, endothelial or germinal cells. The two isoforms of ACE, the two-domain somatic form and the single domain germinal form, convert angiotensin I to angiotensin II, and metabolize kinins and many other biologically active peptides, including substance P, chemotactic peptide and opioid peptides. The broad spectrum of substrates for ACE and its wide distribution throughout the body indicates that this enzyme, in addition to an important role in cardiovascular homeostasis, may be involved in additional physiologic processes such as neovascularization, fertilization, atherosclerosis, kidney and lung fibrosis, myocardial hypertrophy, inflammation and wound healing. Future research should explore the possible functions of tissue ACE and its systemic role as a pressor agent. ACE inhibitors have achieved widespread use in the treatment of hypertension and the protection of end-organ damage in cardiovascular and renal diseases. Potential problems related to side effects and compliance of such therapy need to be addressed. A safer way of producing therapeutic effects is promised by the delivery of the ACE antisense sequences by a vector producing a permanent inhibition of ACE and long-term control of blood pressure in hypertensive patients.

This review summarizes physiology of circulating and local renin-angiotensin system (RAS), enzymatic properties and mechanism of action of angiotensin I converting enzyme inhibitors (ACEIs) on RAS, and implications of ACEIs in anesthetic management of patients treated with these drugs. ACEIs, through their effect on RAS, may improve cardiovascular functions, pulmonary dynamics, and body fluid homeostasis. Thus, ACEIs have become an integral part of management of patients with hypertension, congestive heart failure (CHF) and chronic renal disease. ACEIs, due to differences in their chemical structure, exert different pharmacological actions and can have protective or occasional damaging effects on different organs. The anesthesiologists are commonly involved in the management of patients treated with ACEIs. Thus, the role of ACEIs and their possible interaction with anesthetic agents must be an integral part of clinical decision-making during anesthesia Hemodynamic variation during anesthesia is mainly related to specific effects of anesthetic agents on sympathetic nervous system. Those with preoperative fasting, volume depletion and extended sympathetic blockade can have reduced vascular capacitance resulting in decreased venous return, reduced cardiac output and severe arterial hypotension. Angiotensin II (ANG2) a potent vasoconstrictor may counterbalance such hypotensive effect. During ACE inhibition ANG2 cannot counterbalance this hypotension. Thus, induction of anesthesia may cause severe hypotension in hypovolemic patients specifically in those receiving diuretics as a complement to ACEIs. Recent advances in RAS and the pharmacology of ACEIs have identified some predisposing factors and risks associated with anesthesia in patients treated with ACEIs. Practitioners should be vigilant, and readily have vasopressors, necessary fluids and other resuscitative measures for treatment of unexpected hemodynamic instability during anesthesia and surgery.

The objective of this paper is to present cigarette smoking as the largest risk factor for premature death, the nature of smoking dependence, the methods for its cessation, tobacco intervention training at the medical schools, and importance of the leadership of health care providers in smoking prevention. Effective dependence treatment strategies exist at the level of the practicing physician, at the level of the health care system and at the societal or community level. The key elements of smoking intervention counseling include providing reinforcement through repeated and consistent advice from a team of practitioners to stop smoking, setting a specific quitting date, and scheduling follow-up visits. Unfortunately majority of medical schools teach tobacco intervention skills inadequately. Traditional didactic approaches that include lectures and assigned readings should be reduced in favor of the patientoriented methods. Because smoking as a risk factor is preventable, it is necessary to conduct rigorous preventive measures, including educational programs and various legal actions, such as restrictions on the purchase of tobacco products to teenagers and creation of smoke-free areas. Reduction in the prevalence of smoking among physicians and other health care professionals also significantly influences willingness of society to recognize the health consequences of smoking and perhaps lead to the decline of the smoking epidemic. Therefore, a special attempt should be made to reduce smoking among health professionals, including medical students. The medical students of Yugoslavia made an effort to promote prevention of smoking by introducing A Day Without a Cigarette which is observed on January 31st. The best way to discourage smoking is by approaching children and adolescents since most people start smoking in their teenage years. This age group must recognize the harmful effects of smoking. Banning advertising and other promotional activities of tobacco producers, as well as smoking in hospitals, work places, restaurants, and public transportation is a very strong weapon against smoking.

We investigated the degradation of angiotensin I (Ang I) by guinea pig aqueous humor at physiological pH (pH 7.4) and assessed the activity of responsible enzymes using various enzyme inhibitors. The aqueous humor was incubated with Ang I in the presence or absence of an enzyme inhibitor at 37 degrees C for the appropriate time period. The resulting peptides were analyzed by a Beckman HPLC system with a Waters microBondapak C18 analytical column using a 30-min increasing linear gradient of 10 to 40% acetonitrile containing 0.05% trifluoroacetic acid (TFA) and H2O containing 0.05% TFA at a flow rate of 1 mL/min. Detection was done by absorbance at 214 nm. Angiotensin II (Ang II) was a major product (39.3+/-4.10 nmol x h(-1) mL(-1), n = 5) of Ang I hydrolysis. Traces of angiotensin 1-9, angiotensin IV, and angiotensin 1-7 were also produced. Chymostatin (0.05 mmol/L), EDTA (1 mmol/L), enalaprilat (0.1 mmol/L), and ebelacton B (0.01 mmol/L) inhibited generation of Ang II from Ang I by guinea pig aqueous humor by 89+/-4.6, 56+/-7.6, 33+/-5.1, 20+/-6.5%, respectively. Our findings indicate that guinea pig aqueous humor contains several enzymes that can form Ang II. The chymostatin-sensitive type of enzyme was the most active one found in guinea pig aqueous humor. Angiotensin I converting enzyme, carboxypeptidase A, and deamidase may also contribute to angiotensin II formation in guinea pig ocular fluid.

The objective of this paper is to present cigarette smoking as the greatest risk factor for premature death, the nature of smoking dependence, the methods for its cessation, and to establish the importance of the leadership of health care providers in smoking prevention. Because smoking as a risk factor is preventable, it is necessary to conduct rigorous preventive measures, including educational programs and various legal actions, such as restrictions on the purchase of tobacco products to teenagers and creation of smoke-free areas. Reduction in the prevalence of smoking among physicians and other health care professionals also significantly influences willingness of society to recognize the health consequences of smoking and perhaps lead to the decline of the smoking epidemic. Therefore, a special attempt should be made to reduce smoking among health professionals, including medical students. An effort of medical students in Yugoslavia to promote prevention of smoking in the public by introducing "January 31st--A Day Without a Cigarette" is described. The best way to discourage smoking is by approaching children and adolescents since most people start smoking in their teenage years. This age group must recognize the harmful effects of smoking. Banning advertising and other promotional activities of tobacco producers, as well as smoking in hospitals, workplaces, restaurants, and public transportation is a very strong weapon against smoking.