Proceedings of the Western Pharmacology Society最新文献

Teachers and researchers are valuable resources of universities. A healthy life style includes appropriate utilization of medicines. In this work we explore health status and medicine consumption among a sample of academic employees over 40 years of age at a Mexican university. We analyzed answers to an on line survey in a random sample of academic employees, 40 years and older who work at the National University of Mexico. The 179 item survey was answered from November 2009 to October 2010, by 240 randomly selected academic employees. A section of the questionnaire was oriented toward health issues. We analyzed reported illness, self-perception of health status and medicine consumption. The bodies systems involved most often among those who report any kind of disease were: circulatory and endocrine and/or metabolic, followed by osteomuscular and digestive. Medicinal agents were consumed in the last two weeks by 52% of respondents. Among these, vitamins were consumed by 28%, drugs for pain by 17%, drugs for high blood pressure by 14%, drugs for high cholesterol by 13%, antibiotics by 8%, drugs for diabetes by 5%, cold medicines by 4%. It is suggested that medicinal drugs may not be consumed in situations in which they are indicated, such as in hypercholesterolemia and possibly in hypertension and diabetes. Others, such as vitamins are frequently utilized. Research and interventions should be directed toward better utilization of medicinal drugs.

The aim of this review is to briefly describe some colorimetric methods that are commonly used to evaluate a new chemical entity (NCE) on cell cultures in non-clinical oncology discovery research. These methods have the distinct advantage over other techniques in that they can be applied and used in a cell monolayer or a suspension culture. Both protein assay determination and cell viability assays may be conducted using these culture systems. The viability of cell cultures is routinely assessed by utilizing the metabolic capacity of cells which biochemically convert chemicals (usually color dyes) which can then be conveniently measured at specific wavelengths using a multi-well plate reader. Resazurin (Alamar Blue) is an example of one of these metabolically active compounds. Resazurin is a nontoxic dye that can also be used to measure migration and cellular invasion without resorting to sacrifice of the cells during the test procedure. Another is 5-bromo-2-deoxyuridine (bromodeoxyuridine or BrdU) which is a thymidine analog that incorporates into the DNA of dividing cells during the S-phase of the cell cycle. We will also discuss the colorimetric version of the traditional 3H-thymidine incorporation and immunoenzymatic assay used to measure DNA synthesis and its application to discovery research.

The renin-angiotensin system (RAS) is one of the most important systems in blood pressure homeostasis and pathogenesis of cardiovascular-renal diseases. When blood volume goes down, juxtaglomerular cells in the kidneys secrete renin. Renin stimulates the production of angiotensin I (Ang I), which is then converted to angiotensin II (Ang II). Angiotensin II causes blood vessels to constrict, resulting in increased blood pressure. If the renin angiotensin system is over active, blood pressure will be too high. Most hypotensive drugs are designed to block this system at different points in the pathway. In this study, we developed a mathematical model of the renin-angiotensin system to emulate the response of the renin-angiotensin system in humans. This model consists of a set of differential equations. Special attention is paid to the estimation of all the model parameters from reported experimental data. These equations allow us to model hypertensive and normotensive patients and pharmacotherapeutic approaches to treatment. We show dose-response curves of blood pressure and biochemical components of the renin-angiotensin system. Our results reproduce clinical outcomes. We conclude that mathematical modeling of RAS is a useful approach for gaining insight into the complexities of homeostatic control of arterial pressure and pharmacotherapeutics.

Bee products (BP) have been used for centuries as a diet complement with claimed curative properties. The aim of this study was to determine whether oral administration of BP prevented behavioral, histological, and biochemical alterations, caused by pentylenetetrazole (PTZ)-induced kindling in rats. Male Wistar rats were employed to evaluate seizure latency, number and duration, performance in the open field test, histological alterations and mortality following BP administration. Oral administration of BP at two doses, 30 and 60 mg/kg/day, significantly lengthened latency of both clonic and tonic PTZ-induced seizures, decreased the duration and frequency of seizures and reduced mortality. In the Open Field test, BP treated groups showed increases in the number of crossed squares and rearing counts, and on optimal dose, decreases in fecal boli. Histological analysis showed in PTZ (50 and 80 mg/kg) kindling rats, lungs with inflammatory peribronchiolar, and perialveolar infiltrates. In the liver, mild losses of trabeculae, multi-vesiculated hepatocytes (steatosis) and inflammatory infiltrates in hepatic parenchyma were observed. Interestingly, in the heart, fibers were markedly separated. In testis, stratified epithelium of seminal tubules lost its normal structure, tubules had epithelium loss, spermatids were absent, and spermatogonia and Leydig cells diminished. In PTZ kindling rats treated with BP, the lungs had no inflammatory infiltrates, although the heart showed some inflammatory infiltrates. Remaining structures had normal characteristics. These results, suggest that BP can protect rats from effects of PTZ-induced kindling.

The aim of this study was to evaluate the pharmacological effect of FL-6, a new immunomodulatory drug, in chronic hepatitis immunologically induced in rats via porcine-serum (PS) administration. Thirty-two male Wistar rats (150 g) were divided into 4 experimental groups: (1) Control (PBS 0.5 ml 3-times per week for 8-week); (2) FL-6 (50 ng/kg 3-times per week for 4-week); (3) Hepatitis (PS 373 mg/kg twice per week for 8-week); and (4) Hepatitis + FL-6 (doses as above). Rats were sacrificed at the end of treatment. ALT, AST, ALP and gamma-GT activities, as well as IL-6 and IL-10 levels, were evaluated in serum samples. Glutathione and malondialdehyde were also analyzed. A morphological analysis of liver tissue was carried out. The hepatitis group showed an increase in ALT (1.44-fold), AST (1.28-fold), ALP (1.83-fold), gamma-GT (3.91-fold), IL-6 (2.6-fold) and IL-10 (7.1-fold) levels when compared with controls (p < 0.05). Histopathological analysis revealed an inflammatory response characterized by inflammatory infiltrates and liver damage, which was accompanied by a reduction of 74.8% in glutathione levels (p < 0.05). However, animals with hepatitis treated with FL-6 had a reduction of ALT activity (17.74%), as well as a reduction in IL-6 (24.21%) and IL-10 (30.91%) levels (p < 0.05). These animals showed a reduction in inflammatory response characterized by a decrease in inflammatory infiltrate at the hepatic parenchyma and portal structures; livers showed less damage and a reduction of necrotic and apoptotic hepatocytes. In conclusion, the treatment with FL-6 improved liver function and reduced the inflammatory marker in rats with chronic hepatitis induced by PS-administration.

Ganoderma lucidum, a traditional Chinese medicine, has been shown to target the Central Nervous System. In this work we analyze whether G. lucidum, collected in Mexico, has a protective effect in the hippocampus of rats treated with kainic acid, a neurotoxin that causes seizures and neuronal loss. The aqueous extract of G. lucidum (10 mg/Kg, i.p.) was administered to rats 30 min before kainic acid injection (5 mg/Kg, i.p.). Animals that had received prior treatment with G. lucidum showed no tonic-clonic seizure activity. Histopathological analysis showed a significant decrease in neuronal loss and cellular alterations in the hippocampal CA3 region. Immunohistochemical analysis shows that when using G. lucidum in rats, there is less immunoreactivity for GFAP as well as TNF-alpha and IL-1beta in the CA3 region when compared with rats treated with kainic acid. Our results demonstrate that G. lucidum protects against kainic acid-induced alterations of hippocampal cells and expression of immunological markers in this model of excitotoxicity.

Blindness is a pervasive sensory condition that imposes diverse difficulties to carry on with activities of daily living. In blind individuals, the brain is subjected to a large scale reorganization characterized by expanded cortical territories associated with somatosensory and auditory functions and the recruitment of the former visual areas to perform bimodal somatosensory and auditory integration. This poses obstacles to efforts aimed at reassigning visual functions to the recruited visual cortex in the blind, especially after the end of the ontogentic sensitive period. Devising pharmacological measures to modulate the magnitude of brain plasticity could improve our chances of recovering visual functions in the blind. Here, by using the primary somatosensory cortex (S1) in the rat as a working model, we showed that valproic acid administered through the mother's milk prevents cortical reorganization in blinded rats by delaying neuronal histone de-acetylation. These results suggest that in the future, we might be able to devise epigenetic pharmacological measures that could improve our chances of reassigning visual functions to the once deprived former visual cortex in the blind, by modulating the magnitude of brain plasticity during critical times of development.

Peripheral arterial occlusive disease is described as vascular disorders associated with ischemia and may be the result of an obstructive vascular process or a lost revascularization response. We have shown that gait locomotion analysis by video filming represents an integrative model for the evaluation of mechanisms involved in the process of ischemia-induced revascularization. However, analysis by this method can be subjective and perception errors may be occurring. We present the optimization of a quantifiable, noninvasive, reproducible method that analyzes ankle kinematics in rats using a two-dimensional digital video system. Gait dynamics were filmed in hindlimb ischemic rats with a high speed digital video camera. Images were collected and analyzed at 125 frames per second. An algorithm using interactive data language (IDL) was devised to assess different parameters. In ischemic rats, stride time and knee joint angle remained altered 10 days post-surgery compared with sham animals. Gait kinematics were outlined in a highly reliable way by this computational analysis and corroborated the notion of hindlimb movement recovery associated with the revascularization process.

Low brain serotonin levels and high circulating levels of corticosterone are features of migraine. The 5-HT7 receptor was shown to mediate dilator responses to the 5-HT1B/1D and 5-HT7 receptor agonist, 5-carboxamidotryptamine in the middle meningeal artery of rats. Here we analyzed the effect of serotonin depletion and chronic corticosterone treatment on 5-HT7 receptor-mediated dilatation induced by 5-carboxamidotryptamine in the middle meningeal artery of anesthetized rats. Two weeks before experiments, male Wistar rats received i.c.v. injections of vehicle or the neurotoxin, 5,7-dihydroxytryptamine; upon recovery, animals received a chronic s.c. treatment (2 weeks) with vehicle (1 ml/kg/day) or corticosterone (20 mg/kg/day). At the end of treatments, animals were anesthetized and prepared for recording of blood pressure and blood flow in the middle meningeal artery, and i.v. drug administration. All animals received the 5-HT1B/1D receptor antagonist GR-127935 (1 mg/kg, i.v.) alone or combined with the 5-HT7 receptor antagonist, SB-269970 (1 mg/kg, i.v.). Topical 5-carboxamidotryptamine (0.01-1000 microM) to the exposed dura mater encephala produced decreases in diastolic blood pressure, variable changes in meningeal blood flow and increases in conductance (i.e. dilatation) in the middle meningeal artery. Meningeal dilator responses to 5-carboxamidotryptamine did not differ among treatment groups. In all cases, the combined treatment with GR-127935 + SB-269970 inhibited hypotensive and meningeal dilator responses to 5- carboxamidotryptamine. Together, these data do not support the notion that 5-HT7 receptors mediating dilatation in the middle meningeal artery are regulated by low brain serotonin levels and/or chronically high circulating levels of corticosterone. Further studies are required to elucidate the potential impact of these conditions and the role of 5-HT7 receptors in migraine.

Measuring hepatic metabolic function is critical for detection and treatment of liver failure. Several tests have been widely used to characterize the integrity of liver; however, they do not evaluate the metabolic function of the organ, most requiring multiple blood draws. The purpose of this study was to establish if the ratio of the lidocaine metabolite monoethylglycinexylidide (MEGX) divided by lidocaine concentration at 30 min post intravenous lidocaine administration is a good marker of metabolic activity of the liver. Nine healthy and two partially hepatectomized and auto-transplanted dogs were included in the study. A single 1.5 mg/kg intravenous dose of lidocaine and serum samples were obtained at selected times for 150 minutes. Serum concentrations of lidocaine and MEGX were determined by a validated high-performance liquid chromatographic method. Pharmacokinetic parameters were obtained by non-compartmental methods and ratio of AUC of MEGX divided by AUC of lidocaine was determined for each dog. This ratio was correlated with the ratio of the concentration of the compounds obtained 30 minutes after drug administration. A good concordance was obtained, suggesting that ratio obtained with a single sample may be useful to predict the hepatic metabolism function. To validate the test, dogs hepatectomized and auto-transplanted were plotted and the results obtained were within the values obtained in healthy dogs. These results suggest that ratio of MEGX/lidocaine obtained 30 min after administration could be a good marker of hepatic metabolic function.