Plasma corticotropin releasing hormone during the feeling of induced emotions.

OBJECTIVES: Central neuropeptides modulate behaviour. Plasma levels of neuropeptides may reflect central levels due to specific brain-to-blood transport systems. We purposed to show the modulation of plasma corticotropin releasing hormone (CRH) levels in relation to induced emotions. DESIGN: Three groups were defined. For experimental groups A and B, an emotionally significant movie fragment was projected for 20 min, while no film projection occurred in group C. Peripheral venous blood samples were collected before, 10 and 60 min after the film or at 0 and 30 min for group C. Total CRH was measured in plasma. Personality was evaluated by the Minnesota Multiphasic Personality Inventory (MMPI). RESULTS: Plasma CRH levels did not change in the condition with no movie projection - group C - 346 + or - 198 vs. 327 + or - 143 pg/mL. Plasma CRH levels dramatically increased with the projection of a dramatic movie - group A - 394 + or - 147 vs. 791 + or - 636 vs. 803 + or - 771 pg/mL, p<0.05. Plasma CRH increased less markedly in the condition with the projection of a comic movie - group B - 364 + or - 138 vs. 486 + or - 260 vs. 483 + or - 228 pg/mL, p<0.05 for differences between samples 1 and 3. Baseline plasma CRH was significantly and independently related to the neurotic triad and psychotic dyad - partial r=0.328 and 0.267, respectively, p<0.05. CONCLUSIONS: We conclude that plasma CRH levels increase with experimental emotion induction and that baseline levels are significantly related to behavioural traits. Plasma levels of neuropeptides may reflect central levels and may be useful in clinical medicine and in the study of behavioural disorders.

[Medicine in ancient Mesopotamia - part 2]. / A medicina na Mesopotâmia antiga (2a parte).

The second part embraces exclusively the main characteristics of the medicine in Ancient Mesopotamia, in its main facets: concept of disease, healers and practice. The disease was considered a divine punishment or resultant from a malign influence. Insofar, the medicine began by being preventive, by the use of appropriate amulets or by offerings or sacrifices intending to pacify those malign forces. The treatment of the generality of the diseases privileged the expulsion of those spirits and malign influences from the patient body, purifying it, which was done by the specific intervention of a approximately shipu (clergymanexorcist); not having results, the treatment was continued by the asû (practical healer) that appealed to a group of physical manipulations, limited surgical acts and the administration or application of prescriptions, resultants of the mixture of organic and inorganic substances. In case of failing, the patients (as well as common healthy individuals or rule leaders) could fall back upon a priest diviner (bârû) that, by examination of the organs of an animal especially sacrificed for, would give a final decision about the disease or the future. Besides this more occult facet, nourished in religious faiths and in the magic, the medicine of Ancient Mesopotamia included rational knowledge, certainly as the result of systematic patients observation and semiotic interpretation. From those observations and knowledge referred to the Sumerian period, carefully logged, refined and transmitted to the following generations, it was built a valuable group of texts with the description of symptoms, signs, diagnosis and prognostic of the most common diseases, still identifiable in the present.

From the discovery of the circulation of the blood to the first steps in hemorheology: part 1.

In this article (the first of two on the subject) a brief historical review is presented of the prevailing ideas on the nature of the blood and its circulation from antiquity to the 16th century, when the problem was solved by William Harvey. On the basis of vivisection of various types of animals, Harvey constructed a general and logical model for the whole systemic circulation, which contradicted previous concepts, mainly those that had been put forward by Galen fourteen centuries before. The influence that Galen still exercised on virtually all areas of medicine justified Harvey's hesitations and scruples, forcing him to delay publishing his conclusions for thirteen years. It also explains the controversy with fellow physicians on the subject, which continued until his death. However, through careful observation and painstaking investigation, Harvey demonstrated clearly that the heart was the central organ of the circulatory system, on which depended the propulsion of the blood to the arteries and its subsequent return by different vessels, the veins, to its starting point. The blood coming from the heart was different from that which returned to the organ, the difference (in color and fluidity) being attributed to the presence of constituents which nourished the organism it irrigated. Harvey characterized blood pulsation as the result of the arteries filling with arterial blood during each heart contraction. He demonstrated that the arterial blood left the heart by contraction of the left ventricle, which happened simultaneously with contraction of the right ventricle and, in both, after the contraction of the atria. He confirmed that blood passed through the lung circulation from the right ventricle to the left atrium and from there to the left ventricle. By calculating the volume of blood pumped daily by the heart, Harvey reasoned that the blood could not be consumed by the body and would have to circulate continually through the heart and vascular network. Although Harvey did not confirm the continuity of the circulatory network, he went so far as to hypothesize the existence of minuscule imperceptible passages between arteries and veins, which was later confirmed by Marcello Malpighi, in the form of networks of capillaries. The one-way direction of blood flow was ensured by valves in the heart and veins. The model established by Harvey for blood circulation in animals and extrapolated to humans was confirmed in the following centuries. Malpighi and van Leeuwenhoek, in particular, helped clarify the composition and characteristics of blood and their importance for its perfusion of the different vessels of the circulatory network.

From the discovery of the circulation of the blood to the first steps in hemorheology: part 2.

In the second and last part of this article, the contributions of two more brilliant figures are described in two sections, A and B, respectively Marcello Malpighi and Antonie van Leeuwenhoek. Through the originality of their work, both confirmed the pioneer William Harvey's observations and went on to add important details. Malpighi applied the optical microscope, until then used almost exclusively as a mere curiosity, to the in vitro study of the body tissues of various species. Outstanding among these pioneering observations was the visualization, for the first time, of capillary structures and blood corpuscles, on the basis of which he defined the composition of blood and, also for the first time, the concept of its fluidity. Furthermore, Malpighi confirmed the structural and functional continuity of the systemic circulation, which Harvey had been unable to demonstrate. Although van Leeuwenhoek lacked an academic education, he was able to see, through lenses he built himself, the microscopic details of the organic and inorganic world around him. Among numerous detailed observations of all types of substances, particularly important were the insights that he obtained into the nature of blood and red blood cells, to which he attributed the color of arterial and venous blood. He calculated the size of erythrocytes with striking accuracy. He was able to distinguish arterial from venous blood, confirmed the heart's function as the force behind the propulsion of the blood through the arteries and of the rhythmic nature of the pulse, and elucidated the return of the blood to the heart by different vessels, the veins. He visualized the bifurcation of the arteries into increasingly narrow vessels until they gave way to capillary networks, which in turn became successively wider venous channels. Van Leeuwenhoek demonstrated the existence of arterial-venous anastomoses. He discovered erythrocyte sedimentation and deformability (their shape varying from the original discoid or oval form, observed in larger vascular segments, to flat forms, adapted to the diameter of narrower vessels). In the process he defined the characteristics of red cell circulation and the alterations that follow blood coagulation, and was thus a perceptive pioneer of the concepts of hemorheology applied to medicine.

[Medicine in ancient Mesopotamia--part 1]. / A medicina na Mesopotâmia antiga (1 feminine parte).

The present work summarizes the more elucidating aspects on the foundations and the practice of the medicine in Antique Mesopotamia, since the invention of the writing, more than 5000 thousand years ago, and the beginning of our era. The first part of the article includes a brief perspective about the political and social evolution that characterized those archaic civilizations, as well as the inventions and knowledge further used by the following Humanity's generations. Most of what is known on the subject, as well as the history and political-social events that occurred in the region during that remote epoch, resulted of the laborious decoding of about half a million small clay plates or fragments with text engravings in cuneiform characters that were discovered since the middle of the XIX century in the ruins of the main cities of the Babylonian and Assyrian empires. The second part embraces exclusively the main characteristics of the medicine in Ancient Mesopotamia, in its main facets: concept of disease, healers and practice. The disease was considered a divine punishment or resultant from a malign influence. In that base, the medicine began by being preventive, by the use of appropriate amulets, or by offerings or sacrifices intending to pacify those malign forces. The treatment of the generality of the diseases privileged the expulsion of those spirits and malign influences from the patient body, purifying it, which was done by the specific intervention of an ãshipu (clergyman-exorcist); not having results, the treatment was continued by the asû (practical healer) that appealed to a group of physical manipulations, limited surgical acts and the administration or application of prescriptions, resultants of the mixture of organic and inorganic substances. In case of failing, the patients (as well as individuals or rein leaders) could fall back upon a priest diviner (bârû) who, by examination of the organs of an animal especially sacrificed for the effect, would give a final decision about the disease or the future. Separated this more occult facet, nourished in religious faiths and in the magic, the medicine of Ancient Mesopotamia included rational knowledge, certainly as the result of a systematic patients observation and semiotic interpretation. From those observations and knowledge referred to the Sumerian period, carefully logged, refined and transmitted to the following generations, a valuable collection of texts was built with the description of symptoms, signs, diagnosis and prognostic of the most common diseases, still identifiable in the present.

Leonardo da Vinci and the first hemodynamic observations.

Leonardo da Vinci was a genius whose accomplishments and ideas come down to us today, five centuries later, with the freshness of innovation and the fascination of discovery. This brief review begins with a summary of Leonardo's life and a description of the most important works of art that he bequeathed us, and then concentrates on his last great challenge. There was a point at which Leonardo's passion for art gave way to the study of human anatomy, not only to improve his drawing but to go beyond what had been simply a representation of form to understand the underlying functioning. Among his many interests, we focus on his study of the heart and blood vessels, which he observed carefully in animals and human autopsies, and reproduced in drawings of great quality with annotations of astonishing acuteness. The experience that he had acquired from observing the flow of water in currents and around obstacles, and the conclusions that he drew concerning hydrodynamics, were central to his interpretation of the mechanisms of the heart and of blood flow, to which he devoted much of his time between 1508 and 1513. From these studies, immortalized in drawings of great clarity, come what are acknowledged to be the first hemodynamic records, in which Leonardo demonstrates the characteristics of blood flow in the aorta and great vessels and the importance of blood reflux and the formation of eddies in the sinus in aortic valve his assiduous and careful observations, and his subsequent deductions, Leonardo put forward detailed findings on hemodynamic questions that advanced technology has only recently enabled us to confirm.

[Brief history of rickets and of the discovery of vitamin D]. / Breve história do raquitismo e da descoberta da vitamina D.

Almost eighteen centuries mediated between the first cases of rickets, reported by Soranus and Galeno, and the clarification of the disease aetiology. Due to the outbreak of rickets verified in the 17th century in England, the situation was known as the 'English disease', being its first detailed description presented by Francis Glisson. The growing incidence of rickets with the Industrial Revolution raised speculations about its origin and treatment. The characterization of solar light and luminous spectrum led to the identification of the biological effects of ultraviolet radiation, and to the discovery of phototherapy as an alternative therapeutic process to the solar irradiation. The experimental rickets achieved by Mellanby and McCollum gave support to the concept that this situation could have an origin in a dietary defect. It was also referred an inverse relationship between sun exposure and the incidence of rickets. The identification of the chemical nature of an essential dietary factor with anti-rickets effect (ergocalciferol or vitamin D2), together with another factor with identical properties, but more potent, produced in the skin exposed to sunlight (cholecalciferol or vitamin D3), was essential to the elucidation, prevention and therapy of the disease. The present revision summarizes the history of rickets, the characterization and anti-rickets properties of the light and dietary supplements of lipid nature, and the identification of the major biological forms of vitamin D.

Diet, atherosclerosis and atherothrombotic events.

Epidemiologic studies and clinical trials have shown that diet and, in particular, the consumption of fats, influence the body's metabolism and can affect the development of atherosclerosis and resulting cardiovascular repercussions. A Western-type diet (high in saturated fats, simple sugars and salt, and low in fish, vegetables and fiber) has been associated with proinflammatory, pro-oxidative and prothrombotic tendencies and consequently higher cardiovascular risk. By contrast, a Mediterranean-type diet (with less meat and more fish, fiber, fruit, vegetables, olive oil and wine) appears to explain the lower tendency for cardiovascular disease (and cancer) in those who consume it. Between these two are population groups who prefer diets rich in polyunsaturated fatty acids. The lack of randomized and rigorously controlled population and clinical trials relating types of diet to primary or secondary cardiovascular events may explain some of the disagreements surrounding this subject. It would also explain the lack of results that shed light on diet-dependent mechanisms that may affect the development of atherosclerosis. In general, it is accepted that the morphologic and functional characteristics of vascular endothelium are influenced by the components absorbed from the diet. Prolonged exposure to certain harmful components in the diet may increase the risk of endothelial dysfunction, as shown by a decrease in antithrombotic, antioxidative, antiinflammatory and peripheral vasodilatory modulators, which represents the first step towards the onset of atherosclerosis. Among the main mechanisms involved in endothelial dysfunction are the proinflammatory and prooxidative effects of excess cholesterol, in contrast with the apparent benefit of monounsaturated fatty acids and the less consistent results obtained with polyunsaturated fatty acids.

Cardiovascular risk factors: hemorheologic and hemostatic components.

The original objectives of the Framingham Project are presented along with the concept of cardiovascular risk factors. The traditional risk factors (dyslipidemia, hypertension, smoking, diabetes/glucose intolerance, age, male gender, family history, and obesity) are discussed together with other predisposing factors and biomarkers of cardiovascular disease (circulating in the blood, physical, morphologic and genomic). Of these, certain hemorheologic and hemostatic factors are highlighted as predictors and/or markers of atherosclerosis and subsequent cardiovascular events. The difficulties encountered in defining cardiovascular risks are the result of different abnormalities being given the same name, different methodologies being used for the same problem, and the different effects that a given condition may have on different vascular sectors. Additionally, some risk factors or biomarkers represent single problems, whereas others identify aggregations of indicators, pathophysiologic pathways or etiologies. In the future, genomic and/or proteomic identification of cardiovascular disease mechanisms may help to clarify the situation.

Effects of velnacrine maleate in the leukocyte-endothelial cell interactions in rat cremaster microcirculatory network.

The expression of acetylcholinesterase in proinflammatory cells has supported the hypothesis that this protein plays a role in intercellular adhesion. Previous results of our group show that velnacrine, an acetylcholinesterase inhibitor, increases the number of adherent leukocytes in post-capillary venules of Wistar rats' mesentery muscle. This works intends to evaluate the local application of velnacrine and acetylcholine in the inflammatory response at the microcirculatory network by studying the leukocytes/endothelium interactions in post-capillary venules of Wistar rats' cremaster muscle. The number and the speed of the rolling leukocytes, the number of adherent leukocytes and hemodynamic parameters were determined and also the plasma levels of IL-1beta. The results have shown that in the presence of velnacrine there is a significant increase of the rolling leukocytes (1.28+/-0.39 vs 1.93+/-0.20), as well as an increase of the adherent ones (0.86+/-0.72 vs 1.02+/-0.83). When acetylcholine is adding with velnacrine the number of rolling and adherent leukocytes decreases without changing the IL-1beta plasma circulation induced by velnacrine. Our results suggest an anti-inflammatory role induced by ACh without full efficiency because the rolling leukocytes velocity was reduced without changes in the plasma level of IL-1beta.

Ischemic myocardial disease as an example of a thrombotic event. A historical note.

The definition of myocardial ischemia as a clinical entity of thrombotic etiology was established in 1912 by James Herrick. His proposal was based on the work of William Heberden, who in 1772 defined the clinical profile of angina pectoris, and the observations of Edward Jenner about a century later on intracoronary thrombosis in patients who had died with such symptoms. On the basis of these results, Jenner and Caleb Parry proposed that the main cause of angina were alterations in the coronary arteries, while Marshall Hall, in 1842, attributed sudden death in these patients to interruption of the coronary circulation. The discovery of a common cause for angina pectoris and myocardial infarction, inducing a reduction or interruption of oxygen supply to myocardial tissue, the atherosclerotic etiology of intracoronary lesions, and the importance of plaque fissuring in the sudden formation of intracoronary thrombi, were successive milestones in our understanding in the 20th century, the culmination of the process of meticulous observation begun many years before.

Arterial endothelium and atherothrombogenesis. I--Intact endothelium in vascular and blood homeostasis.

Normal endothelium constitutes a physical and biological barrier between the blood and the vascular wall, and also acts as a sensor and transducer of various endogenous and exogenous factors that modulate the blood circulation. Endothelial activity in a given individual at any particular moment reflects the balance between cardiovascular risk factors, genetic predisposition and vascular protection mechanisms. The availability and activity of endothelium-derived nitric oxide (NO) is a major factor in these mechanisms. Further, vasoactive substances synthesized by the vascular wall and/or by blood cells may affect the behavior of the blood-endothelium interface. Vasomotricity is dependent on the balance between vasodilator substances (particularly prostacylin) and vasoconstrictor products (mainly endothelin-1 and angiotensin II). The coagulation-anticoagulation or fibrinolysis balance is also affected by various different proteins. The mechanisms of these factors, on which blood fluidity depends under normal conditions and with intact endothelium, are discussed, along with mention of potential abnormalities, which will be examined in the second part of this review.

Personality, manual preference and neuroendocrine reactivity in hirsute subjects.

Behavioral and neuroendocrine differences may be postulated in hirsute subjects since central effects of gonadal steroids are well established. We conducted a controlled clinical study with 25 consecutive young hirsute participants compared with 20 consecutive controls. Neuropsychological evaluation included the Minnesota Multiphasic Personality Inventory (MMPI) and the Edinburgh Inventory of Manual Preference (EIMP). Neuroendocrine reactivity was assessed by the adrenocorticotropic hormone (ACTH) and cortisol responses to corticotropin releasing hormone (CRH). Hirsute participants presented a flattened personality profile with lower neurotic triad scores--146 +/- 20 versus 166 +/- 28. Left-hand preference was more common in hirsute participants--4/21 versus 0/20. Decreased ACTH [area under the curve (AUC)--36 +/-2 8 vs. 72 +/- 63 pg/ml h] and cortisol (AUC--18 +/- 4 vs. 25 +/- 10 microg/dl h) responses to CRH were found in the hirsute group. In the hirsute group, higher manual preference scores were associated with lower ACTH responses to CRH, while the opposite association was found in the control group. In the hirsute group, the hyporeactive hypothalamic-pituitary-adrenal (HPA) axis was associated with lower behavior-deviant scores, while in the control group, the hyporeactive HPA axis was associated with more psychopathology. We conclude that personality and HPA axis reactivity are different in hirsute female participants when compared with controls, with a trend for differences regarding handedness. Personality and handedness are differently associated with HPA reactivity. Distinctive features in hirsute participants are probably established very early during ontogenic development.

An in vitro study of adrenaline effect on human erythrocyte properties in both gender.

The possibility that erythrocytes may function as a reservoir for noradrenaline and adrenaline and as a modulator of circulating catecholamine concentrations had been suggested. The aim of this work was to study the adrenaline effect on erythrocyte membrane fluidity, acetylcholinesterase (AChE) enzyme activity, P(50) and erythrocyte deformability and also to verify if the role of adrenaline on erythrocyte properties is sex-dependent. Blood samples from 42 healthy donors were obtained, and its aliquots incubated 30 min without (control) and with 10(-5) M concentrations of adrenaline alone (A(1)) and adrenaline with an alpha and an beta-blocker (A(2)). Results demonstrate that initial AChE values in female are higher (p

Nitric oxide effects on human erythrocytes structural and functional properties--an in vitro study.

NO is present in the blood at 10(-7) M under physiological conditions, but at concentrations higher than 10(-6) M during inflammatory disease states. The aim of this study was to characterize what are the effects of these different NO concentrations on erythrocyte structural and functional properties. Blood was collected from eleven healthy men and incubated with SpermineNONOate in order to expose it during incubation time to NO concentrations between 10(-7) M and 10(-3) M. We measured erythrocyte aggregation and deformability, membrane lipid peroxidation and fluidity, p50, hemoglobin, oxyhemoglobin, methemoglobin concentrations and plasma pH, pO(2), pCO(2), Na(+), K(+) and Ca(2+). When blood was exposed to NO 10(-7) M erythrocyte deformability increase and p50 decrease. In presence of NO 10(-5) M lipid fluidity and p50 decrease. When blood was exposed to NO 10(-3) M methemoglobin concentration increase and erythrocyte deformability and p50 decrease but membrane fluidity and lipid peroxidation were similar to control. In conclusion, dependent of NO concentrations there is different effects on erythrocytes structural and functional properties.

Long-term prognostic value of the hemorheological profile in transmural myocardial infarction survivors: 60-month clinical follow-up.

UNLABELLED: Previous reports have shown several hemorheological and hemostatic abnormalities in acute coronary syndrome survivors. Some of these abnormalities were related to cardiovascular events during a 24-month follow-up. The aim of the present work is to evaluate, in transmural myocardial infarction survivors, the long-term (60 months) prognostic value of the biohemorheological profile determined at hospital discharge. Sixty-four patients (59 men), mean age of 58 +/- 12.0 years, transmural myocardial infarction survivors, were prospectively studied for 60 months (32.0 +/- 17 months, median 33 months). The following cardiovascular events (CVE) were analyzed: death, non-fatal infarction, unstable angina, and stroke. Twenty-nine patients had a CVE (nine died). The following parameters were determined at hospital discharge: plasma viscosity, whole blood viscosity, erythrocyte membrane fluidity, erythrocyte aggregation, protein C, plasminogen inhibitor type I (PAI-1), leukocyte count and elastase. The quartiles were determined for each parameter, grouping patients according to these values. STATISTICS: Group-t-test, Kaplan-Meier survival curve (with log rank test), and Cox logistic regression. RESULTS: 1) Leukocyte count (p < 0.01), protein C activity (p < 0.05) and erythrocyte membrane fluidity (p < 0.05) were predictors of the CVE curve; 2) The higher the value of the leukocyte count quartile, the higher the risk for a CVE (p < 0.05). Patients with a leukocyte count above the median had 4 times more risk for a CVE; 3) The lower the protein C activity, the higher the risk for a CVE. Those with protein C activity lower than the lowest quartile had double the risk; 4) The higher the membrane polarization value (membrane rigidity), the higher the risk of a CVE; 5) By multivariate analysis the 3 parameters were independent predictors of a CVE. CONCLUSION: In the present group of transmural myocardial infarction survivors a close relationship was established between hemorheologic, hemostatic and inflammatory factors and the cardiovascular events curve during long-term follow-up.

Beta-estradiol effect on erythrocyte aggregation--a controlled in vitro study.

The purpose of this in vitro study was to assess the effect of 17beta-estradiol on hemorheologic parameters, namely on erythrocyte aggregation and deformability and membrane fluidity. Blood samples from 65 women (aged 57 +/- 4 years) undergoing postmenopausal hormone replacement therapy were obtained and were incubated for 5 min in absence and presence of 17beta-estradiol 10(-5) M. The measured parameters were the erythrocyte aggregation (EAI) and deformability (EI), the acetylcholinesterase activity (AChE), the plasma pH and osmolality and the erythrocyte membrane fluidity assessed by fluorescence polarization with two probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and (1-(4-(trimethylamino)-phenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH). Data analysis was performed using t-Student and Pearson correlation analysis. A statistically significant decrease of the EAI (15.8 +/- 3.02 vs 13.45 +/- 2.3; p<0.001) and an increase of the EI (51.39 +/- 5.64 vs 52.06 +/- 5.36; p<0.01) at shear stress of 30 Pa in presence of 17beta-estradiol 10(-5) M was obtained. There was a decrease in membrane fluidity in 45 blood samples (DPH) and in the other 20 an increase, when beta-estradiol 10(-5) M was present. In vitro beta-estradiol 10(-5) M decreased erythrocyte aggregation in blood samples of postmenopausal women undergoing hormone therapy, which could prevent high blood viscosity and, consequently, cardiovascular events.

Ethanol and erythrocyte membrane interaction: a hemorheologic perspective.

Previous studies have documented structural and functional changes induced by ethanol-erythrocyte membrane interaction. In order to perform an in vitro study on the effect of different ethanol concentrations on erythrocyte hemorheologic properties, blood samples were collected from 21 male donors at the Hospital of Santa Maria. Whole blood aliquots were incubated with ethanol solutions of rising concentrations. The following parameters were measured: erythrocyte aggregation, haemoglobin, carboxyhaemoglobin and methaemoglobin concentrations, hematocrit, plasma osmolality and erythrocyte membrane fluidity (fluorescence polarisation probes TMA-DPH and DPH). With ethanol blood concentrations of 45 mM a rise in plasma osmolality (0.352 Osm/kg H2O vs 0.310 Osm/kg H2O; p < 0.001) was verified. With 67 mM concentration a decrease of erythrocyte aggregation (11.03 vs 12.81; p < 0.05) and an increase in plasma osmolality (0.380 Osm/kg H2O vs 0.310 Osm/kg H2O; p < 0.001) were obtained. In conclusion, ethanol only changes erythrocyte aggregation for a concentration of 67 mM. These data could lead to future changes in therapeutic approaches to situations such as alcoholic coma.

Red blood cell membrane integrity in primary open angle glaucoma: ex vivo and in vitro studies.

PURPOSE: There is increasing evidence that abnormal perfusion of the optic nerve head is an important factor involved in the pathophysiology of glaucoma. Transport and distribution of oxygen to the tissues takes place through the erythrocyte membrane. Red blood cell (RBC) acetylcholinesterase (AChE) is a marker of RBC membrane integrity. The aim of this study was to find out whether RBC membrane integrity is preserved in primary open angle glaucoma (POAG), and whether it is modified by the use of topical timolol maleate and pilocarpine. METHOD: RBC AChE activity was determined ex vivo by Kaplan's spectrophotometric method in 19 POAG patients undergoing topical treatment for glaucoma with timolol, pilocarpine or a combination of the two drugs, and compared with that in 20 controls. To assess the effect of antiglaucomatous therapy in our findings, we carried out an in vitro study in 26 non-glaucomatous patients in which we measured RBC AChE activity after incubation of blood with either timolol maleate, pilocarpine or a combination of the two drugs, using the same spectrophotometric method. RESULTS: There was a significant increase in RBC AChE enzyme activity in POAG patients compared with the control group (p < 0.002). However, timolol and pilocarpine, individually or in combination, have the opposite effect, significantly decreasing RBC AChE activity (p < 0.05). CONCLUSION: This change in RBC AChE enzyme activity could suggest alterations in RBC membrane integrity in primary open angle glaucoma. Whether or not this finding has implications regarding the microcirculation at the optic nerve head needs to be investigated further.