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1.
Rev. bras. cir. cardiovasc ; 34(3): 290-296, Jun. 2019. tab, graf
Article in English | LILACS | ID: biblio-1013469

ABSTRACT

Abstract Objective: In this study, we aimed to examine the effects of amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts in coronary artery bypass graft surgeries. Methods: 59 patients (40 males and 19 females; mean age 65.1 years, distribution: 45-84 years) who had coronary artery bypass graft surgery between February 2014 and May 2016 were included in the study. After the saphenous vein grafts with intact and denuded endothelium were precontracted with 3×10-6M phenylephrine, amitriptyline, fluoxetine and tranylcypromine were cumulatively added to isolated organ baths in the range of 10-11-3x10-5M, while venlafaxine was added in the range of 10-9-3×10-5M. Then, the antidepressant-induced relaxation responses were recorded isometrically. Results: While the relaxation response of amitriptyline at -6.42 (Log M) was 74.6%, the response at -6.32 (Log M) was 75.5%. While the relaxation response at -6.46 (Log M) of fluoxetine was 68.02%, the response at -6.02 (Log M) was 72.12%. While the relaxation response of tranylcypromine at -7.53 (Log M) was 61.13%, the response at -7.23 (Log M) was 65.53%. While the relaxation response of venlafaxine at -6.21 (Log M) was 29.98%, the response at -5.90 (Log M) was 32.96%. Conclusion: The maximum relaxation at minimum and maximum therapeutic concentrations was obtained with amitriptyline, fluoxetine and tranylcypromine, and the minimum relaxation was obtained with venlafaxine. The relaxation responses were independent of the endothelium.


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Saphenous Vein/drug effects , Saphenous Vein/transplantation , Tranylcypromine/pharmacology , Fluoxetine/pharmacology , Amitriptyline/pharmacology , Antidepressive Agents/pharmacology , Reference Values , Vasodilation/drug effects , Endothelium, Vascular/drug effects , Coronary Artery Bypass/methods , Analysis of Variance , Transplants/drug effects , Venlafaxine Hydrochloride/pharmacology , Muscle, Smooth, Vascular/drug effects
2.
J. appl. oral sci ; 25(2): 159-167, Mar.-Apr. 2017. tab, graf
Article in English | LILACS, BBO | ID: biblio-841178

ABSTRACT

Abstract Reports have indicated that serotonin plays an important role in cell migration and differentiation during the organogenesis of several tissues, including the oral types. Administration of selective serotonin reuptake inhibitor (SSRI) drugs during pregnancy could affect the delivery of serotonin to embryonic tissues altering its development. Objective This study aimed to assess the effects of fluoxetine, a selective serotonin reuptake inhibitor, on the formation of the periodontal ligament during pregnancy and lactation in rat pups. Material and Methods Twelve pregnant rats of Wistar lineage were divided into four study groups. In the control group, 0.9% sodium chloride solution was administered orally, throughout the entire period of the 21 days of pregnancy (CG group) and in the CGL group, it was administrated during pregnancy and lactation (from day 1 of pregnancy to the 21st day after birth). Fluoxetine was administered orally at the dose of 20 mg/kg in a group treated during pregnancy only (FG group), and during pregnancy and lactation (FGL group). Histometrical, histochemical and immunohistochemical analysis of the maxillary first molar periodontium region of the 24 rat pups was made under light microscopy, and periodontal ligament collagen was qualitatively evaluated under a polarizing light microscope. Results The quantity of fibroblasts (p=0.006), osteoblasts (p=0.027) and cementoblasts (p=0.001) was reduced in pups from the rats that received fluoxetine during pregnancy and lactation. No alterations were seen in the collagen fibers. Conclusion These findings suggest that periodontal tissue may be sensitive to fluoxetine, and its interference in reducing periodontal cells depends on exposure time during lactation.


Subject(s)
Animals , Male , Female , Pregnancy , Osteogenesis/drug effects , Periodontal Ligament/drug effects , Fluoxetine/pharmacology , Serotonin Uptake Inhibitors/pharmacology , Periodontal Ligament/growth & development , Periodontal Ligament/embryology , Time Factors , Lactation , Immunohistochemistry , Random Allocation , Rats, Wistar , Maternal Exposure , Fibrillar Collagens/analysis , Alveolar Process/drug effects , Alveolar Process/embryology
3.
RELAMPA, Rev. Lat.-Am. Marcapasso Arritm ; 28(1): 27-30, jan.-mar.2015.
Article in Portuguese | LILACS | ID: lil-773029

ABSTRACT

A síndrome do QT longo induzida por fármacos é uma condição potencialmente fatal, capaz decausar morte súbita como primeira manifestação clínica. Relatamos o caso de paciente jovem que evoluiu comparada cardiorrespiratória em fibrilação ventricular durante internação hospitalar, 24 horas após nefrolitotripsiaextracorpórea. Durante a avaliação foi observado intervalo QT corrigido aumentado de 580 ms e uso de fórmulapara emagrecer que continha fluoxetina 30 mg. Após suspensão da medicação houve normalização do QT,optando-se pelo uso de cardiodesfibrilador implantável pelo alto risco de recorrência da fibrilação ventricular.A síndrome do QT longo pode se manifestar após o uso de fármacos para o tratamento de outras afecções,ressaltando a importância da anamnese rigorosa em busca de antecedentes de morte súbita, assim como darealização de eletrocardiografia antes da introdução de fármacos específicos, de forma a identificar possíveis casosassintomáticos de síndrome do QT longo.


Drug-induced long QT syndrome is a potentially fatal condition that can cause sudden death as a firstclinical manifestation. We report the case of a young patient evolved with cardiorespiratory arrest in ventricularfibrillation during hospitalization, 24 hours after extracorporeal nephrolithotripsy. The patient had an increasedcorrected QT interval of 580 ms and was on weight loss medication containing fluoxetine 30 mg. The QT intervalnormalized after withdrawal of the medication and we chose to use an implantable cardioverter defibrillator dueto the high risk of reoccurrence of ventricular fibrillation. Long QT syndrome may manifest after drug therapyfor other diseases, highlighting the importance of obtaining a through family history of sudden death as well asan ECG before using specific drugs, to identify possible asymptomatic cases of long QT syndrome.


Subject(s)
Humans , Male , Female , Child , Adolescent , Adult , Stress, Psychological/therapy , Long QT Syndrome/diagnosis , Tachycardia, Ventricular/complications , Electrocardiography, Ambulatory/nursing , Fluoxetine/adverse effects , Fluoxetine/pharmacology , Lidocaine/administration & dosage , Magnesium Sulfate/administration & dosage
4.
Int. j. morphol ; 32(3): 751-755, Sept. 2014. ilus
Article in English | LILACS | ID: lil-728261

ABSTRACT

The pharmacological manipulation with selective inhibitor of serotonin reuptake (SSRIs) can modify the operation of the serotonergic system and may facilitate or inhibit the action of this system, inducing changes in the morphology of the skeletal muscle of rats. The objective of this study was to evaluate the action of the treatment with fluoxetine during the critical period of the animal´s life on development of the soleus and lateral gastrocnemius muscles, under the aspects of weight, the number of nuclei of myocyte cells and cross-sectional area of muscle fibers. Twenty four (30 and 90-day-old) male Wistar rats were used. They were treated with saline solution (NaCl 0.9%; 1 ml/100 g of body weight) or fluoxetine (10 mg; 1 ml/100g of body weight). The animals were divided in Saline Group (GS-30 and GS-90) and Fluoxetine Group (GF-30 and GF-90). The fluoxetine group showed a reduction on weight (g) of soleus (p=0.046) and lateral gastrocnemius (p=0.02) muscles in rats with 90 days. A lesser number of myonuclei was observed in fluoxetine group than saline group of 30 days (soleus, p<0.001; lateral gastrocnemius, p0.007) and 90 days (soleus, p=0.002; lateral gastrocnemius, p0.038). The cross section area of fluoxetine groups is also smaller than the saline groups with 30 days (soleus, p=0.03; lateral gastrocnemius, p=0.041) and 90 days (soleus, p=0.042; lateral gastrocnemius, p=0.012). The treatment of fluoxetine during the critical period of development of the nervous system of rats, causes early changes in the structure of muscle fibers that seem to be related to reducing the weight of the soleus and gastrocnemius muscles only in late stage of the animal's life. Thus, the dosage used ISRS, suggests an inhibitory effect of 5-HT in relation to variables on the development of the skeletal muscle tissue of rats.


La manipulación farmacológica con inhibidores selectivos de la recaptación de la serotonina (ISRS) pueden cambiar el funcionamento del sistema serotoninérgico y facilitar o inhibir la acción de este sistema, induciendo cambios en la morfología del músculo esquelético de ratones. El objetivo fue analizar los efectos de la manipulación farmacológica neonatal con fluoxetina en el desarrollo de la masa muscular, número de núcleos y área de la sección transversa de las fibras de los músculos sóleo y gastrocnemio lateral. Se utilizaron 24 ratones Wistar machos, de 30 y 90 días de edad, tratados con solución salina (NaCl 0,9%, 1m/100 g de peso corporal) y fluoxetina (1 mg; 1 ml/100 g de peso corporal). Los animales fueron divididos en grupos con solución salina (GS-30 y GS-90) y fluoxetina (GF-30 y GF-90). El grupo tratado con fluoxetina mostró una reducción de peso (g) de los músculos sóleo (p=0,0046) y gastrocnemio lateral (p=0,02) en 90 días. Además, se observó en este mismo grupo una reducción de núcleos en 30 días (M. sóleo, p<0,001; M. gastrocnemio lateral, p0,007) así como en el período de 90 días (M. sóleo, p=0,002; M. gastrocnemio lateral, p0,038). También se observó reducción del área de la sección transversal en los animales tratados con fluoxetina durante el período de 30 días (M. sóleo, p=0,03; M. gastrocnemio lateral, p= 0,041;) y 90 días (M. sóleo, p=0,042; M. gastrocnemio lateral, p=0,012). El tratamiento con fluoxetina durante el período crítico del desarrollo del sistema nervioso de ratones, induce cambios prematuros en la estructura de la fibra muscular, los que parecen estar relacionados con la reducción de peso de los músculos sóleo y gastrocnemio en una fase tardía de vida del animal. En consecuencia, la dosis utilizada de ISRS, sugiere un efecto inhibidor de la 5-HT, en relación a las variables estudiadas sobre el desarrollo del tejido muscular esquelético de ratones.


Subject(s)
Animals , Male , Rats , Fluoxetine/pharmacology , Serotonin Uptake Inhibitors/pharmacology , Muscle, Skeletal/drug effects , Organ Size/drug effects , Rats, Wistar , Muscle Fibers, Skeletal/drug effects , Muscle Cells/drug effects
5.
Braz. j. med. biol. res ; 47(7): 554-559, 07/2014. tab, graf
Article in English | LILACS | ID: lil-712973

ABSTRACT

Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33±4.7 and -31±5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35±5.4 and -31±5.5%, respectively, with an increase in blood pressure +26.3±2.5; 3 mg/kg sertraline reduced RSNA by -59.4±8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central.


Subject(s)
Animals , Male , Fluoxetine/administration & dosage , Kidney/drug effects , Paroxetine/administration & dosage , Serotonin Uptake Inhibitors/administration & dosage , Sertraline/administration & dosage , Sympathetic Nervous System/drug effects , Antidepressive Agents/administration & dosage , Antidepressive Agents/pharmacology , Arterial Pressure/drug effects , Baroreflex/drug effects , Cardiovascular Physiological Phenomena/drug effects , Fluoxetine/pharmacology , Heart Rate/drug effects , Kidney/innervation , Kidney/surgery , Paroxetine/pharmacology , Rats, Wistar , Respiratory Rate/drug effects , Serotonin Uptake Inhibitors/pharmacology , Sertraline/pharmacology , Vital Signs/drug effects
6.
Int. braz. j. urol ; 40(1): 100-108, Jan-Feb/2014. tab, graf
Article in English | LILACS | ID: lil-704169

ABSTRACT

Introduction: The aim of this study was to evaluate the effect of selective serotonin reuptake inhibitors (SSRIs) on testicular tissue and serum malondialdehyde (MDA) levels in rats. Materials and methods: A total of 40 male Wistar albino rats, 5.5-6 months old, were equally divided at random into five groups: group 1 was the control group, group 2 received sertraline 10mg/kg (p.o), group 3 was administered fluoxetine 10mg/kg (p.o), group 4 received escitalopram 10mg/kg (p.o), and group 5 (n = 8) was administered paroxetine 20mg/kg. Each dose was administered orally for two months. Johnsen’s criteria were used to categorize spermatogenesis. Johnsen’s method assigns a score of 1 to 10 to each tubule cross-section examined. In this system, a Johnsen score of 9 and 10 indicates normal histology. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were evaluated. Serum MDA levels were also measured. Results: The mean Johnsen scores were 9.36 ± 0.33, 9.29 ± 0.32, 8.86 ± 0.48, 9.10 ± 0.56, and 8.33 ± 0.90 in control group, sertraline group, fluoxetine group, escitalopram group, and paroxetine group, respectively. The Johnsen score was significantly lower for paroxetine group compared with the control group (p < 0.05). The mean FSH level increased only in the sertraline group. With the exception of the fluoxetine group, the testosterone levels were lower in all groups compared with the control group. The total testosterone level was significantly lower in the sertraline group compared with the control group [40.87 (22.37-46.8) vs. 15.87 (13.53-19.88), p < 0.01]. There were no significant differences between the groups with respect to the MDA and LH levels (p = 0.090 and p = 0.092). Conclusion: These data suggest that SSRIs have a negative effect on testicular tissues. This negative impact is markedly greater in the paroxetine group. To determine the exact ...


Subject(s)
Animals , Male , Rats , Malondialdehyde/blood , Oxidative Stress/drug effects , Serotonin Uptake Inhibitors/pharmacology , Testis/drug effects , Citalopram/pharmacology , Fluoxetine/pharmacology , Follicle Stimulating Hormone/blood , Luteinizing Hormone/blood , Paroxetine/pharmacology , Random Allocation , Rats, Wistar , Sertraline/pharmacology , Spermatogenesis/drug effects , Testosterone/blood
7.
Indian J Exp Biol ; 2013 Jun; 51(6): 435-443
Article in English | IMSEAR | ID: sea-147611

ABSTRACT

The compound 6o (at 0.5, 1 and 2 mg/kg, ip) with optimum log P and pA2 value, was subjected to forced swim test (FST) and tail suspension test (TST). The compound 6o significantly reduced the duration of immobility in mice without affecting the base line locomotion in actophotometer. Moreover, 6o (2 mg/kg, ip), potentiated the 5-hydroxytryptophan (5-HTP)-induced head twitch responses in mice and at 1 and 2 mg/kg, ip antagonized the reserpine-induced hypothermia (RIH) in rats. In interaction studies with various standard drugs/ligands using FST, 6o (1 and 2 mg/kg, ip) potentiated the anti-depressant effect fluoxetine (5 mg/kg, ip) and reversed the depressant effect of parthenolide (1 mg/kg, ip) by reducing the duration of immobility. Furthermore, 6o (1 and 2 mg/kg, ip) potentiated the effect of bupropion (10 mg/kg, ip) in TST. The behavioural anomalies of the olfactory bulbectomised (OBX) rats were augmented by chronic 6o (1 and 2 mg/kg) treatment as observed from the modified open field test (parameters: ambulation, rearing, fecal pellet). The results suggest that compound 6o exhibited anti-depressant like effect in rodent models of depression.


Subject(s)
Animals , Antidepressive Agents/pharmacology , Anxiety/drug therapy , Behavior, Animal/drug effects , Depression/drug therapy , Fluoxetine/pharmacology , Guinea Pigs , Mice , Motor Activity/drug effects , Olfactory Bulb/drug effects , Paroxetine/pharmacology , Quinoxalines/pharmacology , Rats , Rats, Wistar , Serotonin 5-HT3 Receptor Antagonists/pharmacology , Swimming
8.
New Iraqi Journal of Medicine [The]. 2013; 9 (2): 7-11
in English | IMEMR | ID: emr-127366

ABSTRACT

Atherosclerosis is a progressive inflammatory disorder of the arterial wall that is characterized by focal lipid rich deposits of atheroma with possible correlation with sedative hypnotics in decreasing atherogenesis. This study was performed in Al-Kadhimiya teaching hospital from February 2009 to June 2009 on sixty healthy males who were allocated to six groups. Each group was given one of the following agents: Magnesium sulfate [MgSo4], acetic acid, Meprobamate, Fluoxetine in addition to Simvastatin and water. Clinical manifestations like [arterial blood pressure, radial pulsation], lipid profiles [serum cholesterol, triglycerides, HDL, LDL and VLDL] total free radicals and platelets function tests are the parameters used in this study. All the tested agents reduce both the serum cholesterol concentration and total blood free radicals significantly; also they decrease both platelet count and adhesion test significantly. Both MgSo4 and Meprobamate lowered blood pressure and serum triglyceride concentration significantly, at the same time HDL concentration significantly changed by Fluoxetine when these parameters measured before and after treatment for 15 days. MgSo4, acetic acid, Meprobamate and Fluoxetine were found to have anti-arthrogenic activity and the possibility to be used clinically in atherosclerosis


Subject(s)
Humans , Male , Atherosclerosis/prevention & control , Fluoxetine/pharmacology , Magnesium Sulfate/pharmacology , Acetic Acid/pharmacology , Meprobamate/pharmacology
9.
Braz. j. med. biol. res ; 45(10): 948-954, Oct. 2012. ilus, tab
Article in English | LILACS | ID: lil-647747

ABSTRACT

Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT4 receptor and the serotonin transporter (SERT) as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times) between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT4 receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05) and increased 5-HT4 receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05). Treatment with fluoxetine (10 mg·kg-1·day-1, days 36-42), tegaserod (1 mg·kg-1·day-1, day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT4 receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01) but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654). These results indicate that both the 5-HT4 receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT level.


Subject(s)
Animals , Male , Rats , Hypersensitivity/metabolism , Irritable Bowel Syndrome/metabolism , /metabolism , Serotonin Plasma Membrane Transport Proteins/metabolism , Viscera/metabolism , Animals, Newborn , Blotting, Western , Chronic Disease , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Fluoxetine/pharmacology , Hypersensitivity/drug therapy , Immunohistochemistry , Irritable Bowel Syndrome/chemically induced , Irritable Bowel Syndrome/drug therapy , Rats, Sprague-Dawley , Severity of Illness Index , Serotonin Uptake Inhibitors/pharmacology
10.
Rev. bras. educ. fís. esp ; 26(3): 375-381, jul.-set. 2012. ilus
Article in Portuguese | LILACS | ID: lil-649615

ABSTRACT

Trabalhos de diferentes autores constataram que, um aumento na concentração de serotonina (5-HT) no cérebro, durante exercício físico intenso e prolongado, está diretamente relacionado a um prejuízo na função do Sistema Nervoso Central (SNC), com correspondente desenvolvimento da fadiga e consequente diminuição do desempenho. No presente trabalho, 10 ratos Wistar foram submetidos a sessões de corrida até o esgotamento físico em esteira rolante. Os protocolos experimentais foram divididos em quatro fases: Fase 1 - avaliação do tempo médio de corrida dos animais até o esgotamento físico; Fase 2 - avaliação do tempo médio de corrida dos animais até o esgotamento físico, sob tratamento com fluoxetina; Fase 3 - "washout" de sete dias; Fase 4 - "washout" de 14 dias. Este estudo sugere que a administração crônica de fluoxetina aumenta substancialmente o tempo médio de corrida até o esgotamento físico em ratos submetidos a exercício em esteira rolante.


Works of different authors have been shown that an increase in the concentration of serotonin (5-HT) in the brain during intense and long-term physical exercise, is directly associated with a harm in the function of the Central Nervous System (CNS), with corresponding development of the fatigue and consequence decrease of the performance. In the present work, 10 rats Wistar were submitted to run-sessions until the exhaustion in treadmill. The experimental protocols were splited in 4 phases: Phase 1: evaluation of the range run-time of the animals until the physical exhaustion. Phase 2: evaluation of the range run-time of the animals until the physical exhaustion on treatment with fluoxetine. Phase 3: washout seven days. Phase 4 washout 14 days. The present study suggest that chronic administration of fluoxetine increase substantially the run-time until the physical exhaustion in rats submitted to exercises in treadmill.


Las obras de diferentes autores encontraron que un aumento en la concentración de la serotonina (5-HT) en el cerebro durante el ejercicio intenso y prolongado está directamente relacionado con deterioro de la función del Sistema Nervioso Central (SNC), con el correspondiente desarrollo de la fatiga y su consecuente reducción en el rendimiento. En este estudio, 10 ratas Wistar fueron sometidas a la ejecución de sesiones en una cinta hasta el agotamiento físico. Los protocolos experimentales fueron divididos en cuatro fases: Fase 1 - Evaluación de la carrera media de los animales al agotamiento físico, la Fase 2 - Evaluación de la carrera media de los animales al agotamiento físico, están en tratamiento con fluoxetina, la Fase 3 - "lavado "de siete días; Fase 4 -" lavado "de 14 días. Este estudio sugiere que la administración crónica de fluoxetina incrementa sustancialmente la tarifa media del agotamiento físico en ratas sometidas a ejercicio en una caminadora.


Subject(s)
Animals , Rats , Fatigue , Fluoxetine/pharmacology , Physical Conditioning, Animal , Running , Serotonin/physiology , Rats, Wistar
11.
Einstein (Säo Paulo) ; 10(1): 110-115, jan.-mar. 2012. graf, ilus
Article in English, Portuguese | LILACS | ID: lil-621521

ABSTRACT

Oral anticoagulants are among the drugs with the greatest number of drug interactions. The concomitant use of several medications is a common practice in patients with cardiovascular problems, who often also present with depression; therefore, the probability of an interaction occurring between warfarin and the antidepressants is high, and may result in increased or decreased anticoagulant activity. Since the possible interactions between these two classes of drugs have been poorly explored in literature, with a risk to the patients who use them, we reviewed the pharmacology of warfarin and its possible interactions with antidepressants. Of the antidepressants analyzed, those that showed relevant effects on the interaction with warfarin were, in decreasing order: paroxetine, venlafaxine, fluoxetine, and duloxetine.


Os anticoagulantes orais estão entre as drogas com maior número de interações medicamentosas. O uso concomitante de vários medicamentos é uma prática comum em pacientes com problemas cardiovasculares, os quais frequentemente também apresentam depressão; assim, a probabilidade de ocorrer alguma interação entre a varfarina e os antidepressivos é bem expressiva, podendo resultar em um aumento ou uma diminuição da atividade anticoagulante. Como as possíveis interações entre essas duas classes de medicamentos se mostraram pouco exploradas na literatura, com risco aos pacientes que fazem uso delas, revisamos a farmacologia da varfarina e suas possíveis interações com antidepressivos. Dos antidepressivos analisados, os que apresentaram efeitos relevantes na interação com a varfarina foram, em ordem decrescente: paroxetina, venlafaxina, fluoxetina e duloxetina.


Subject(s)
Humans , Anticoagulants/pharmacology , Antidepressive Agents/pharmacology , Warfarin/pharmacology , Administration, Oral , Anticoagulants/adverse effects , Anticoagulants/pharmacokinetics , Anticoagulants/therapeutic use , Biotransformation/drug effects , Cyclohexanols/pharmacology , /metabolism , Drug Interactions , Fluoxetine/pharmacology , Hemorrhage/chemically induced , Paroxetine/pharmacology , Thiophenes/pharmacology , Thrombophilia/drug therapy , Vitamin K/antagonists & inhibitors , Warfarin/adverse effects , Warfarin/pharmacokinetics , Warfarin/therapeutic use
12.
Yonsei Medical Journal ; : 842-848, 2012.
Article in English | WPRIM | ID: wpr-93569

ABSTRACT

PURPOSE: Pulmonary Kv channels are thought to play a crucial role in the regulation of cell proliferation and apoptosis. Previous studies have shown that fluoxetine upregulated the expression of Kv1.5 and prevented pulmonary arterial hypertension in monocrotaline-induced or hypoxia-induced rats and mice. The current study was designed to test how fluoxetine regulates Kv1.5 channels, subsequently promoting apoptosis in human PASMCs cultured in vitro. MATERIALS AND METHODS: Human PASMCs were incubated with low-serum DMEM, ET-1, and fluoxetine with and without ET-1 separately for 72 h. Then the proliferation, apoptosis, and expression of TRPC1 and Kv1.5 were detected. RESULTS: In the ET-1 induced group, the upregulation of TRPC1 and down regulation of Kv1.5 enhanced proliferation and anti-apoptosis, which was reversed when treated with fluoxetine. The decreased expression of TRPC1 increased the expression of Kv1.5, subsequently inhibiting proliferation while promoting apoptosis. CONCLUSION: The results from the present study suggested that fluoxetine protects against big endothelin-1 induced anti-apoptosis and rescues Kv1.5 channels in human pulmonary arterial smooth muscle cells, potentially by decreasing intracellular concentrations of Ca2+.


Subject(s)
Apoptosis/drug effects , Blotting, Western , Cell Proliferation/drug effects , Cells, Cultured , Endothelin-1/pharmacology , Flow Cytometry , Fluoxetine/pharmacology , Humans , /genetics , Muscle, Smooth, Vascular/cytology , Pulmonary Artery/cytology , Reverse Transcriptase Polymerase Chain Reaction
13.
Clinics ; 66(9): 1605-1610, 2011. ilus, tab
Article in English | LILACS | ID: lil-604301

ABSTRACT

OBJECTIVES: To evaluate the effects of antidepressants and pilocarpine on the quantity of myoepithelial cells and on the proliferation index of the epithelial cells of rat parotid glands. INTRODUCTION: Hyposalivation, xerostomia, and alterations in saliva composition are important clinical side effects related to the use of antidepressants. METHODS: Ninety male Wistar rats were allocated to nine groups. The control groups received saline for 30 (group C30) or 60 days (group C60) or pilocarpine for 60 days (group Pilo). The experimental groups were administered fluoxetine (group F30) or venlafaxine for 30 days (group V30); fluoxetine (group FS60) or venlafaxine (group VS60) with saline for 60 days; or fluoxetine (group FP60) or venlafaxine (group VP60) with pilocarpine for 60 days. Parotid gland specimens were processed, and the immunohistochemical expression of calponin and proliferating cell nuclear anti-antigen on the myoepithelial and parenchymal cells, respectively, was evaluated. Analysis of variance (ANOVA), Tukey HSD and Games-Howell tests were applied to detect differences among groups (p<0.05). RESULTS: Compared with the controls, chronic exposure to antidepressants was associated with an increase in the number of positively stained cells for calponin. In addition, venlafaxine administration for 30 days was associated with an increase in the number of positively stained cells for proliferating cell nuclear anti-antigen. Fluoxetine and pilocarpine (group FP60) induced a significant decrease in the number of positively stained cells for calponin compared with all other groups. CONCLUSIONS: The number of positively stained cells for calponin increased after chronic administration of antidepressants. The proliferation index of the epithelial cells of rat parotid glands was not altered by the use of antidepressants for 60 days.


Subject(s)
Animals , Male , Rats , Antidepressive Agents/pharmacology , Calcium-Binding Proteins/metabolism , Epithelial Cells/drug effects , Microfilament Proteins/metabolism , Parotid Gland/drug effects , Pilocarpine/pharmacology , Proliferating Cell Nuclear Antigen/metabolism , Analysis of Variance , Cell Proliferation/drug effects , Cyclohexanols/pharmacology , Epithelial Cells/metabolism , Epithelial Cells/pathology , Fluoxetine/pharmacology , Muscarinic Agonists/pharmacology , Parotid Gland/cytology , Parotid Gland/metabolism , Random Allocation , Rats, Wistar , Time Factors
14.
Rev. bras. psiquiatr ; 32(2): 152-158, jun. 2010. tab
Article in English | LILACS | ID: lil-554008

ABSTRACT

OBJECTIVE: To evaluate morphological alterations in rat fetuses treated with fluoxetine and imipramine during the "critical" period of gestation. METHOD: Fifteen female rats were separated into three groups (n = 5) and treated with 10 mg/kg/day of test substances on the ninth, tenth and eleventh day of pregnancy: G1, fluoxetine; G2, imipramine hydrochloride; G3 (control), saline. On day 21, cesarean sections were performed to release the fetuses, whose bodies were weighed and macroscopically analyzed. The placenta was also weighed. The fetuses were then fixed and their encephala removed and weighed. Sections of the frontal lobe were taken for histological neuron counting. RESULTS: G1 and G2 showed the highest fetal body weight. Placental weight showed statistical differences (p < 0.01): G1 weighed more than G2 and G3. Otherwise, G2 exhibited the highest encephalon weight, statistically differing from G3 (control) and fluoxetine-treated G1 (p < 0.01). However, G1 did not statistically (p > 0.01) differ from the control group. G3 showed the highest number of neurons per area when compared to G1 and G2 (p < 0.01). CONCLUSION: The use of antidepressants in rats caused an increase in fetal weight and a decrease in the number of fetal frontal lobe neurons, thus suggesting that the use of antidepressants by pregnant women can induce depression in fetuses due to alterations in their neural development.


OBJETIVO: Avaliar as possíveis alterações ocorridas em nível macroscópico e microscópico de fetos de ratas submetidas ao tratamento com fluoxetina e imipramina durante o período "crítico" da gestação. MÉTODO: Quinze ratas, posteriormente ao acasalamento, foram divididas em três grupos experimentais (n = 5): G1, tratadas com 10mg/kg/dia de fluoxetina; G2, tratadas com 10mg/kg/dia de cloridrato de imipramina, e G3 (controle), tratadas com 10mg/kg/dia de solução fisiológica a 0,9 por cento, no 9º, 10º e 11º dias de prenhez das ratas. Posteriormente à cesária, no 21º dia de prenhez, analisou-se macroscopicamente o peso fetal e placentário. Os fetos foram fixados e houve a remoção do encéfalo para pesagem e preparação das lâminas do tecido neuronal para contagem de neurônios do lobo frontal. RESULTADOS: O G1 e G2 apresentaram maior peso fetal. O G1 apresentou maior peso placentário, diferindo do G2 e G3 (p < 0,01). De forma diferente, o G2 possuiu maior peso encefálico, diferindo do G3 e G1 (p < 0,01). G1 não diferiu estatisticamente do grupo controle (p > 0,01). O G3 exibiu maior número de neurônios, por área, do lobo frontal em relação a G1 e G2 (p < 0,01). CONCLUSÃO: A adoção dos antidepressivos causou, nos fetos, aumento de peso e redução da contagem de neurônios do lobo frontal, sugerindo que a indicação de antidepressivos às gestantes pode induzir a depressão nos fetos por alterações em seu neurodesenvolvimento.


Subject(s)
Animals , Female , Pregnancy , Rats , Antidepressive Agents/pharmacology , Brain/drug effects , Dopamine Uptake Inhibitors/pharmacology , Fetus/drug effects , Fluoxetine/pharmacology , Imipramine/pharmacology , Antidepressive Agents/therapeutic use , Brain/embryology , Fetal Weight/drug effects , Fetus/anatomy & histology , Placenta/drug effects , Rats, Wistar
15.
Rev. chil. neurocir ; 34: 11-15, jun. 2010. tab, graf
Article in Spanish | LILACS | ID: lil-600348

ABSTRACT

El síndrome doloroso miofascial (SDM) es la causa más frecuente de dolor músculo esquelético persistente presentándose con lumbalgia, cefalea, cervicalgia y dolor escapular. Con una mayor incidencia en mujeres 3:1, siendo su etiología y fisiopatología aún desconocidas. La fluoxetina, un inhibidor selectivo de la recaptación de serotonina, ha demostrado tener efecto analgésico y mejor tolerancia en el dolor tipo crónico. En esta serie de casos prospectiva y multicéntrica, se evaluó la eficacia de la fluoxetina en el tratamiento del SDM. Los pacientes recibieron fluoxetina 20 mg diarios como coadyuvante a su terapia analgésica habitual. El grado de respuesta fue del 97 por ciento en una muestra de 37 pacientes, asociándose a mejoría clínica evidente con reducción del número de analgésicos empleados e intensidad del dolor (p<0.001), evidenciando su efecto analgésico a las 1.5 semanas y antidepresivo a las 2-3 semanas. En conclusión, la fluoxetina es activa en pacientes con SDM, sin efectos adversos y buena tolerancia.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Antidepressive Agents/therapeutic use , Facial Pain/diagnosis , Facial Pain/etiology , Facial Pain/physiopathology , Facial Pain/therapy , Fluoxetine/adverse effects , Fluoxetine/pharmacology , Musculoskeletal System/pathology
16.
Int. j. morphol ; 27(3): 899-903, sept. 2009. ilus
Article in English | LILACS | ID: lil-598954

ABSTRACT

The TMJ has been to the Dental community a key point in the search of knowledge, being it part of the temporomandibular joint complex and of the estomatognathic system which are in charge of the mastication, speech, swallowing, as well as participation in breathing and taste perception. For the majority of the women in serious state of depression, which do not respond psychotherapeutic treatment, pharmacological treatment it's applied. The antidepressants serotonin selective reuptake inhibitors (SSRIs) are the most recommended in these cases. The teratogenic effect of the SSRIs is considered controversial, studies done with women who used these drugs during the pregnancy showed that the respiratory and central nervous systems are the most affected, was also recorded a deficit of body growth and the decrease of the encephalon and skull measures. In the present study, our goal was to assess whether the administration of Fluoxetine during the pregnancy modified the embryology and morphology of the TMJ of rats. For that, 16 Wistar female rats from the Nutrition Department of the UFPE vivarium were selected; 8 for the control group, which received daily 0.9 percent of saline in subcutaneous dose of 10ml/g, with schedules previously established after daily weighing and 8 for the experimental one that were treated with fluoxetine hydrochloride with the dose of 10mg/Kg in a volume 10ml/g of weight, were injected subcutaneously with the same standards established for the control group. It was observed, with this dose that the embryological development of the TMJ, especially of the mandibular condyle, does not present any difference between the degree of maturation of the tissue that forms the TMJ, especially of the condyle between the treated and control groups.


La ATM ha sido para la comunidad odontológica un punto clave en la búsqueda del conocimiento, dado que forma parte del complejo articular temporomandibular y del sistema estomatognático, los cuales se encargan de la masticación, fonación y deglución, así como la participación en la respiración y de la percepción gustativa. Para la mayoría de las mujeres con cuadros graves de depresión, que no responden al tratamiento psicoterapéutico, el tratamiento farmacológico es aplicado. Los antidepresivos del grupo de los Inhibidores Selectivos de Recaptación de Serotonina (ISRSs) son los más comúnmente recomendados en estos casos. El efecto teratogénico de los ISRSs es considerado controversial. Estudios realizados en mujeres que utilizaron estas drogas durante la gestación mostraron que los sistemas respiratorios y nervioso central son los más afectados, también fue constatado un déficit de crecimiento corporal, encefálico y disminución de las medidas craneales. En el presente estudio, nuestro objetivo fue evaluar si la administración de fluoxetina durante la gestación modifica la embriología y la morfología de la ATM de ratas de laboratorio. Para este fin, 16 ratas Wistar del bioterio de nutrición de la UFPE fueron seleccionadas: 8 para el grupo de control, las cuales recibieron diariamente solución fisiológica a 0,9 por ciento en aplicaciones subcutáneas en la dosis de 10ml/g, en horarios previamente establecidos después de pesaje diario y 8 para el experimental, las que fueron tratadas con clorhidrato de fluoxetina en la dosis de 10mg/kg, en un volumen de 10ml/g, inyectados por vía subcutánea en los mismos estándares establecidos para el grupo de control. Se observó, que con esta dosis el desarrollo embriológico de la ATM, especialmente del cóndilo mandibular, no presentó ninguna diferencia entre el grado de maduración de los tejidos que forman la ATM, especialmente del cóndilo, entre los grupos tratado y grupo control.


Subject(s)
Animals , Male , Female , Pregnancy , Infant, Newborn , Infant , Temporomandibular Joint , Temporomandibular Joint/metabolism , Embryonic Development , Serotonin Uptake Inhibitors/metabolism , Serotonin Uptake Inhibitors/therapeutic use , Depression/metabolism , Depression/drug therapy , Fluoxetine/adverse effects , Fluoxetine/pharmacology , Fluoxetine/therapeutic use , Rats, Wistar/embryology
17.
Rev. bras. cir. cardiovasc ; 24(2): 173-179, abr.-jun. 2009. ilus, tab
Article in English | LILACS | ID: lil-525565

ABSTRACT

OBJECTIVE: To assess fluoxetine effects on mitochondrial structure of the right ventricle in rats exposed to cold stress. METHODS: The experimental study procedures were performed in 250-300g male EPM-Wistar rats. Rats (n=40) were divided into four groups: 1) Control group (CON); 2) Fluoxetine (FLU); 3) Induced hypothermia (IH) and; 4) Induced hypothermia treated with fluoxetine (IHF). Animals of FLU group were treated by the administration of gavages containing 0.75 mg/kg/day fluoxetine during 40 days. The induced hypothermia was obtained by maintaining the groups 3 and 4 in a freezer at -8ºC for 4 hours. The animals were sacrificed and fragments of the right ventricle (RV) were removed and processed prior to performing electron microscopic analysis. RESULTS: The ultrastructural changes in cardiomyocytes were quantified through the number of mitochondrial cristae pattern (cristolysis). The CON (3.85 percent), FLU (4.47 percent) and IHF (8.4 percent) groups showed a normal cellular structure aspect with preserved cardiomyocytes cytoarchitecture and continuous sarcoplasmic membrane integrity. On the other hand, the IH (34.4 percent) group showed mitochondrial edema and lysis in cristae. CONCLUSION: The ultrastructural analysis revealed that fluoxetine strongly prevents mitochondrial cristolysis in rat heart, suggesting a protector effect under cold stress condition.


OBJETIVO: Analisar os efeitos da fluoxetina sobre a estrutura mitocondrial do ventrículo direito de ratos expostos ao estresse pelo frio. MÉTODOS: Os procedimentos do estudo foram realizados em ratos Wistar-EPM (250-300g) machos. Os ratos (n=40) foram divididos em quatro grupos: 1) Controle (CON); 2) Fluoxetina (FLU); 3) Induzidos à hipotermia (IH) e; 4) Induzidos à hipotermia tratados com fluoxetina (IHF). O grupo FLU foi tratado com gavagem contendo 0,75 mg/kg/dia de fluoxetina durante 40 dias. O estresse induzido pelo frio foi realizado mantendo os grupos 3 e 4 em um freezer (-8ºC) por quatro horas. Os animais foram sacrificados e fragmentos do ventrículo direito (VD) foram removidos e processados antes de serem conduzidos para a microscopia eletrônica. RESULTADOS: As alterações ultraestruturais dos cardiomiócitos foram quantificadas pelo número padrão de cristas mitocondriais (cristólises). Os grupos CON (3,85 por cento), FLU (4,47 por cento) e IHF (8,4 por cento) mostraram aspecto normal de suas estruturas celulares com a citoarquitetura dos cardiomiócitos preservada com integridade sarcoplasmática contínua. Por outro lado, o grupo IH (34,4 por cento) apresentou edema mitocondrial e lise nas cristas. CONCLUSÃO: A análise ultraestrutural revelou que a fluoxetina previne fortemente cristólises mitocondriais em miocárdio de ratos, sugerindo possível efeito protetor na condição de estresse induzido pelo frio.


Subject(s)
Animals , Male , Rats , Fluoxetine/pharmacology , Hypothermia, Induced , Mitochondria, Heart/drug effects , Myocytes, Cardiac/drug effects , Protective Agents/pharmacology , Cold Temperature , Heart Ventricles/drug effects , Heart Ventricles/ultrastructure , Models, Animal , Mitochondria, Heart/ultrastructure , Myocytes, Cardiac/ultrastructure , Rats, Wistar
18.
Arq. neuropsiquiatr ; 66(4): 844-847, dez. 2008. graf
Article in English | LILACS | ID: lil-500566

ABSTRACT

The objective of this study was evaluate the anxiety and locomotor activity (LA) in 52 Wistar adult male rats, being 26 treated with fluoxetine (10 mg/Kg - sc) in the neonatal period. These same rats received foot shock (FS) (1.6-mA - 2-s) in the 90th day. The anxiety and LA were appraised by plus-maze. The time spent in the open arms was used as anxiety index and the LA was measured by number of entries in closed arms (NECA) and the total of entries (TE). T-test was used with p<0.05 and expresses data in mean±SEM. There were reductions with the fluoxetine group in the NECA (2.35±0.33) and in the TE (3.96±0.61) compared to the controls (4.65±0.52) and (6.96±0.94). The neonatal administration of fluoxetine did not alter the anxiety, but reduced the LA in the animals that received FS.


O objetivo deste estudo foi avaliar a ansiedade e a atividade locomotora (AL) em 52 ratos Wistar adultos machos, sendo 26 tratados no período neonatal com fluoxetina (10 mg/Kg - sc) e no 90º dia, receberam estímulos elétricos nas patas (1,6-mA-2-s). A ansiedade e a AL foram avaliadas por meio do labirinto elevado em cruz. O tempo de permanência dos animais nos braços abertos (BA) foi utilizado como índice de ansiedade e a AL medida pelo número de entradas nos braços fechados (NEBF) e pelo total de entradas (TE) nos BA e BF. O teste t foi utilizado, com (p<0,05) e os dados apresentados em média±erro padrão. Os animais tratados reduziram o NEBF (2,35±0,33) e o TE (3,96±0,61) comparados a seus controles (4,65±0,52) e (6,96±0,94). A administração neonatal de fluoxetina não alterou a ansiedade, mas diminuiu a AL dos animais que receberam EE.


Subject(s)
Animals , Male , Rats , Anxiety/drug therapy , Fluoxetine/pharmacology , Maze Learning/drug effects , Motor Activity/drug effects , Serotonin Uptake Inhibitors/pharmacology , Animals, Newborn , Rats, Wistar
19.
Int. j. morphol ; 26(1): 51-62, 2008. ilus, tab
Article in English | LILACS | ID: lil-558592

ABSTRACT

The aim of the present study was to test the hypothesis that the application of fluoxetine a highly selective serotonin reuptake inhibitor (SSRI) ¡ in rats during the suckling period induces changes in testicular development. Groups of newborn male rats were randomly assigned with different doses of fluoxetine 24 hours after birth. Each litter stayed with its respective mother during 21 days. Body weight (BW) was measured daily from the 1st -21st day to calculate daily doses of fluoxetine. 5 mg (T1), 10 mg (T2) 20 mg (T3) or deionized water, were injected intraperitoneally. On the 21st day, animals were heparinized, anesthetized and blood was collected by cardiac puncture to determine by radioimmunoassay the follicle stimulating hormone (FSH) levels. Testis were removed, weighed, and processed for morphometric analysis. Fluoxetine groups presented decreased body and testicular weight when compared with the control group on the 21st day. Our findings show that the manipulation of the serotoninergic system with fluoxetine during the critical period of testicular development alters the Sertoli cell population and all testicular parameters related to this cell.


El propósito del presente estudio fue probar la hipótesis que el uso de fluoxetina - un inhibidor altamente selectivo de la serotonina (SSRI) - induce cambios en el desarrollo testicular de ratas durante el período de amamantamiento. Los grupos de ratas macho recién nacidas fueron asignados aleatoriamente con diversas dosis del fluoxetina, 24 horas después del nacimiento. Cada cría permanecía con su madre respectiva durante 21 días. El peso corporal (BW) fue medido diariamente desde el 21día 1 al 21, para calcular las dosis diarias del fluoxetina. 5 mg (T1), 10 mg (T2) y 20 (T3) o agua desionizada fueron inyectados intraperitonealmente. En el día 21, los animales fueron tratados con heparina, anestesiados y la sangre fue recogida por punción cardiaca para determinar por radioinmunoanálisis los niveles de la hormona folículo-estimulante (FSH). Los testículos fueron retirados, pesados y procesados para el análisis morfométrico. Los grupos tratados con fluoxetina presentaron disminución del tamaño y peso testiculares, en comparación con el grupo control día 21. Los resultados demuestran que la manipulación del sistema serotoninérgico con fluoxetina durante el período crítico del desarrollo testicular, altera la población de células de Sertoli y todos los parámetros testiculares relacionados con este tipo celular.


Subject(s)
Animals , Male , Rats , Sertoli Cells , Fluoxetine/pharmacology , Serotonin Uptake Inhibitors/pharmacology , Testis , Breast Feeding , Fluoxetine/administration & dosage , Serotonin Uptake Inhibitors/administration & dosage , Rats, Wistar , Time Factors , Testis/growth & development
20.
Rio de Janeiro; s.n; 2008. [102] p. tab.
Thesis in Portuguese | LILACS | ID: lil-505581

ABSTRACT

Neste trabalho enfocaremos o consumo de antidepressivos, buscando questionar a posição mais comumente aceita para explicar o alto consumo dessas substâncias, que geralmente responsabiliza os ardilosos estratagemas das indústrias farmacêuticas ou a hegemonia da psiquiatria biológica na medicina. Acreditamos que as respostas devem ser buscadas em análises mais profundas, e não simplesmente na demonização desse ou daquele ator social considerado isoladamente, pois admitimos que no consumo se constrói parte da racionalidade integrativa e comunicativa de uma sociedade, logo, pensar o consumo implica em um enfoque dos sujeitos enquanto consumidores, indivíduos e cidadãos. Partindo dessas considerações, analisaremos o consumo de antidepressivos pela ótica dos usuários através da análise do conteúdo de um site de relacionamentos muito popular na internet brasileira, conhecido como Orkut.


Subject(s)
Humans , Antidepressive Agents/adverse effects , Antidepressive Agents/pharmacology , Antidepressive Agents/metabolism , Self Medication/adverse effects , Self Medication/trends , Fluoxetine/pharmacology , Fluoxetine/therapeutic use , Anthropology , Anti-Anxiety Agents/blood , Anti-Anxiety Agents/therapeutic use , Discussion Forums , Drug Industry/ethics , Drug Industry/trends , Internet , Psychotropic Drugs/blood , Psychotropic Drugs/therapeutic use , Sertraline/therapeutic use , Drug Utilization/ethics , Drug Utilization/trends
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