Evaluation of anxiolytic effect of combination of tramadol with gabapentin and pregabalin in Wistar rats

Background: Anxiety is a widespread disorder that approximately 18% of the population experience at some stage in their lives. Pain is a common stimulus that induces anxiety in both animals and human beings. Combination of drugs with good anti-anxiety and analgesic effect can be used for the treatment of chronic pain induced anxiety, post-operative, and procedure-related pain-induced anxiety. Aims and Objectives: The study was conducted to evaluate the anxiolytic activity of combination of gabapentin with tramadol, pregabalin with tramadol compared to standard fluoxetine, in elevated plus maze (EPM) and light-dark arena (LDA) models of anxiety in Wistar albino rats. Materials and Methods: Twenty-four male or female albino Wistar rats from Central Animal House, MRMC, Kalaburagi, were utilized. Fluoxetine 10 mg/kg, gabapentin 30 mg/kg, tramadol 30 mg/kg, and pregabalin 30 mg/kg were used. Eddy’s hot plate method used for inducing anxiety. EPM and LDA models were used to study the effect of drugs in reducing the pain and anxiety. Results: The present study showed that the exposure to hot plate induces pain, creates anxiety, and reduces locomotor and explorative activity among the rats when exposed to hot plate. There was reduction in anxiety after drug administration, in fluoxetine and gabapentin with tramadol groups with >75% increase in entry into the light chamber or open arm at least once or more during the time period of 5 min when compared to hot plate post-exposure readings. Whereas in pregabalin and tramadol group, it was observed that 25% increase in entry of rats into open arm at least once during the time period of 5 min and 25% decrease in entry of rats into light chamber as compared to those rats after exposure to hot plate. Conclusion: Our study has demonstrated that tramadol, pregabalin, and gabapentin have got analgesic as well as anti-anxiety effects in rats when given in combination. All these experimental data, together with the previous experimental studies and the results reported in this work, suggest that combination of these drugs could be more effective in treating anxiety-related disorders such as chronic pain, pain-induced anxiety, post-operative, and procedure-related pain-induced anxiety with minimal side effects. Further dose ranging studies and models might be necessary to better understand the effects of these drugs in combination.

Astragaloside IV for Heart Failure: Preclinical Evidence and Possible Mechanisms, A Systematic Review and Meta-Analysis / 中国结合医学杂志

OBJECTIVE@#To explore the cardioprotective effects of astragaloside IV (AS-IV) in heart failure (HF).@*METHODS@#PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, Web of Science, Wanfang Database, Chinese Bio-medical Literature and Retrieval System (SinoMed), China Science and Technology Journal Database (VIP), and China National Knowledge Infrastructure (CNKI) were searched from inception to November 1, 2021 for animal experiments to explore AS-IV in treating HF in rats or mice. The left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular weight-to-body weight (LVW/BW) and B-type brain natriuretic peptide (BNP) were recorded. The qualities of included studies were assessed by the risk of bias according to the Cochrane handbook. Meta-analysis was performed using Stata 13.0.@*RESULTS@#Twenty-one articles involving 558 animals were considered. Compared with the control group, AS-IV improved cardiac function, specifically by increasing LVEF (mean difference (MD)=6.97, 95% confidence interval (CI)=5.92 to 8.03, P<0.05; fixed effects model) and LVFS (MD=7.01, 95% CI=5.84 to 8.81, P<0.05; fixed effects model), and decreasing LVEDD (MD=-4.24, 95% CI=-4.74 to -3.76, P<0.05; random effects model) and LVESD (MD=-4.18, 95% CI=-5.26 to -3.10, P<0.05; fixed effects model). In addition, the BNP and LVW/BW levels were decreased in the AS-IV treatment group (MD=-9.18, 95% CI=-14.13 to -4.22, P<0.05; random effects model; MD=-1.91, 95% CI=-2.42 to -1.39, P<0.05; random effects model).@*CONCLUSIONS@#AS-IV is a promising therapeutic agent for HF. However, this conclusion needs to be clinically validated in the future.

Effect of "Teddy Bear Simulation Hospital" in cultivating the humanistic care ability for pre-clinical medical students / 中华医学教育探索杂志

The cultivation of medical students' humanistic care ability is one of the most important tasks of medical education. In this study, "Teddy Bear Simulation Hospital" was launched to cultivate humanistic care ability for pre-clinical medical students in the early stage. Firstly, pre-clinical students were organized to visit clinical functional zoning and diagnosis and treatment processes, listen to pediatrician lectures, and understand the diagnosis and treatment process of pediatric patients. Then, students were organized to build a simulated hospital for kids in the kindergarten with reference to the actual situation and carry out simulated diagnosis and treatment. In the process of implementation, students divide the labor, make the plan and take the action independently. After the simulation scenario was created, the kids played the role of parents of the sick children, and their favorite plush toy was pretended to be the sick baby; the medical students played the various roles of the medical staffs in the simulated hospital to carry out various diagnosis and treatment activities in an orderly manner. The results showed that the activity has provided a safe and friendly simulation diagnosis and treatment platform for pre-clinical students. In the interaction with children, the humanistic care ability of the students was significantly improved.

Anxiolytic-like activity of Aloysia virgatavar. platyphylla leaves extract in mice / Actividad ansiolítica del extracto de hojas de Aloysia virgatavar. platyphylla en ratones

Background: Medicinal plants are part of traditional medicine and should be considered a therapeutic alternative for mental diseases. Several plants belonging to the Verbenaceae family have proved useful in treating general anxiety disorders, the most prevalent psychiatric disorders. Objective: This research aimed to verify the extract's safety, the effect on general behavior, and the effect on sleeping time, as well as to evaluate the anxiolytic-like effect of the methanol extract of Aloysia virgata var. platyphylla (Avp), in mice. Methodology: The toxicity test was done according to the OECD guide (mice groups n=5), and general behavior was observed during the assay. Sleeping time was assessed using the pentobarbital-induced hypnosis method (n=8). Male Swiss albino mice (n=6) were treated with 50 to 400 mg/kg of Avp extract and diazepam as a control. The anxiolytic-like effect was tested through the hole board and elevated plus-maze test. Results: The Avp extract has no side effects in tested doses, and no central nervous system depressant activity was noted. A. virgatavar. platyphyllaincreased exploration (number and time) in the hole board. In the elevated plus-maze, increased number and time into open arms were evidenced compared to the control group. Conclusion: With all these results, we concluded that the Avp extract is safe and has a potential anxiolytic-like activity in the animal model used

Antecedentes: Las plantas medicinales forman parte de la medicina tradicional y deben ser consideradas una alternativa terapéutica para las enfermedades mentales. Varias plantas pertenecientes a la familia Verbenaceae han demostrado su utilidad en el tratamiento de los trastornos de ansiedad, uno de los trastornos psiquiátricos más prevalentes. Objetivo: Esta investigación tuvo como objetivo verificar la seguridad del extracto, el efecto sobre el comportamiento general y el efecto sobre el tiempo de sueño, así como evaluar el efecto tipo ansiolítico del extracto metanólico de Aloysia virgata var. platyphylla(Avp), en ratones. Metodología: La prueba de toxicidad se realizó de acuerdo con la guía de la OCDE (grupos de ratones n=5), y se observó el comportamiento general durante el ensayo. El tiempo de sueño se evaluó mediante el método de hipnosis inducida por pentobarbital (n=8). Se trataron ratones albinos suizos macho (n=6) con 50 a 400 mg/kg de extracto de Avp y diazepam como control. El efecto ansiolítico se probó a través de la placa perforada y prueba del laberinto en cruz elevado. Resultados: El extracto de Avp no tiene efectos secundarios en las dosis probadas y no se observó actividad depresora del sistema nervioso central. A. virgata var. platyphylla aumentó la exploración (número y tiempo) en el tablero de agujeros. En el laberinto en cruz elevado, se evidenció un mayor número y tiempo en los brazos abiertos en comparación con el grupo de control. Conclusión: Con todos estos resultados, concluimos que el extracto de Avp es seguro y tiene una potencial actividad ansiolítica en el modelo animal utilizado

Feasibility study on developing clinical pediatrics curriculum for medical students engaged in long schooling system in the pre-clinical stage / 中华医学教育探索杂志

Objective:To analyze the feasibility of developing clinical pediatrics curriculum for pediatric students at the pre-clinical stage, and to provide a basis for the subsequent curriculum construction.Methods:A total of 90 pediatric medical students were enrolled, including pre-clinical group (G1, third semester of the second year, n=47) and the clinical clerkship group (G2, seventh semester of the fourth year, n=43). A questionnaire survey was conducted to compare the two groups from three aspects: clinical interest, learning methods and learning ability. And 24 and 20 students were randomly selected from the two groups to participate a clinical course respectively. Both of the formative evaluation and in-class test were carried out to compare the learning performance and learning effect between G1 and G2. SPSS 22.0 was used for data analysis. The counting data were described by case number and rate, and the frequency between groups was compared by chi-square test. When the chi-square test condition is not met, Fisher's exact test was performed. Normal distribution test was carried out for measurement data. Two independent sample t test was conducted for the comparison between groups of normal distribution data and Mann-Whitney U test for the comparison between groups of skewed distribution respectively. Results:There was no significant difference in clinical interest and pre-clinical interest between the two groups (Fisher's exact probability method, P=0.252, 1.000). There were partial differences in learning methods: G1 spent more time learning after class ( Z=-2.36, P=0.018), learned more in spare time ( Z=2.53, P=0.011), learned more on the homework ( P=0.020), and had a higher preview rate ( Z=-5.07, P < 0.001). There were also partial differences in learning ability: G2 had better literature retrieval ability ( χ2=10.57, P=0.001); G2 had higher scores on class and extended class performance ( t=-3.18, P=0.004; t=-10.14, P<0.001). In terms of learning effect, G2 scored higher scores on only one multiple choice question ( t=-2.46, P=0.022). Conclusion:The pediatrics students at the pre-clinical stage have certain interest and ability to receive clinical pediatrics courses. Sufficient pre-class preparation and appropriate curriculum design are helpful to the early cultivation of student's clinical thinking.

Subjective sleep parameters in prodromal Alzheimer's disease: a case-control study

Objective: People with Alzheimer's disease (AD) dementia have impaired sleep. However, the characteristics of sleep in the early stages of AD are not well known, and studies with the aid of biomarkers are lacking. We assessed the subjective sleep characteristics of non-demented older adults and compared their amyloid profiles. Methods: We enrolled 30 participants aged ≥ 60 years, with no dementia or major clinical and psychiatric diseases. They underwent [11C]PiB-PET-CT, neuropsychological evaluations, and completed two standardized sleep assessments (Pittsburgh Sleep Quality Inventory and Epworth Sleep Scale). Results: Comparative analysis of subjective sleep parameters across the two groups showed longer times in bed (p = 0.024) and reduced sleep efficiency (p = 0.05) in individuals with positive amyloid. No differences in other subjective sleep parameters were observed. We also found that people with multiple-domain mild cognitive impairment (MCI) had shorter self-reported total sleep times (p = 0.034) and worse overall sleep quality (p = 0.027) compared to those with single-domain MCI. Conclusions: Older adults testing positive for amyloid had a longer time in bed and lower sleep efficiency, regardless of cognitive status. In parallel, individuals with multiple-domain MCI reported shorter sleep duration and lower overall sleep quality.

Combination Of Sgt (Small Group Teaching) And Pal (Peer Assisted Learning) Approach To Facilitate Learning Among Mbbs Students From A Private University In Malaysia During Pre-Clinical Years

@#Didactic lecture promotes passive learning and fails to motivate students. Small group learning has been widely recommended as it helps to refine understanding of complex issues, to solve the problems, develop critical thinking and apply knowledge to new situations. PALS – a “peer assisted learning” mode where in students discuss in groups and learn from each other. They get motivated and set a platform, which encourages them to communicate and do problem solving. The present study was aimed to evaluate the effectiveness of small group teaching (SGT) and peer assisted learning (PAL) approach among pre clinical medical students. Small groups of students were selected for this study out of the big batch of students pursuing 2nd year MBBS program at AIMST University who were undergoing “respiratory system” block. At the end of lecture-based sessions, a few topics were selected for SGT- PAL session. Students were asked to complete the pretest questions on the selected topics and they were then explained the topics selected for this session. Students had SGT PAL on those selected topics. Then they completed the post test questions on the same topic. Responses obtained for the pre- test and post-test questions were analyzed using SPSS using paired t test and the perceptions on their own understanding using marginal homogeneity test, both showed a significant improvement. SGT and PAL approach helped students to improve understanding of important concepts and can be adopted more widely as an alternative to lectures.

Universiti Sains Malaysia (USM) Pre-clinical Medical Students’ Guidance and Counselling Needs Questionnaire: A Confirmatory Factor Analysis

@#Introduction: The USM Pre-clinical medical students’ guidance and counselling needs questionnaire (USM-MSGCN-Q) is an English-language guidance and counselling needs questionnaire which was developed specifically for pre-clinical medical students. The aim of this study is to highlight the construct validity of USM-MSGCN-Q among pre-clinical medical students. Methods: In June 2017, a cross-sectional study on 208 pre-clinical medical students was conducted in Universiti Sains Malaysia (USM). This self-administered USM-MSGNC-Q consisted of four constructs and 20 items with a 5-point Likert scale within each item. A confirmatory factor analysis was employed to test the hypothesized measurement model. Results: The final measurement model fitted the data well. The four-factor model initially consisted of 20 items however, it was reduced to 18 items with the goodness of fit indices suggesting good model fit (RMSEA 0.89, GFI .915 and ChiSq/df 2.642). Internal consistency reliability (Cronbach’s alpha) was 0.879 for self-leadership skills, 0.929 for communication skills, 0.871 for learning skills, and 0.870 for psychological coping skills. The overall Cronbach’s value was 0.922. Respective composite reliability values were 0.879,0.952,0.879 and 0.835 while the Average Variance Extracted values were 0.729, 0.911, 0.595 and 0.630. Conclusion: This study has confirmed that self-leadership, communication, learning and psychological coping skills were the components of guidance and counselling needs which influences the effectiveness of guidance and counselling sessions with pre-clinical medical students.

Chemical characterization and toxicological assessment of hydroethanolic extract of Mandevilla velame xylopodium

Abstract The present study was aimed to characterize the chemical profile and evaluate the cytotoxicity and sub-chronic toxicity of the hydroethanolic extract of the xylopodium Mandevilla velame (A.St.-Hil.) Pichon, Apocynaceae. Chemical profile was analyzed by high performance liquid chromatography. Cytotoxic potential of hydroethanolic extract of the xylopodium M. velame was evaluated using Chinese hamster ovary cells. The sub-chronic assessment was done on rats with hydroethanolic extract of the xylopodium M. velame (50, 200 and 800 mg/kg) was orally administered daily for 30 consecutive days. High performance liquid chromatography analysis confirmed the presence of gallic acid, ellagic acid, catechin, epigallocatechin gallate, naringin, myricetin, quercetin and naringenin. hydroethanolic extract of the xylopodium M. velame tested concentrations did not alter the viability of Chinese hamster ovary cells. In the sub-chronic test, 50 and 200 mg/kg were safe, but there were significant changes in relation to weight gain and water consumption by animals that received 800 mg/kg of hydroethanolic extract of the xylopodium M. velame. Among the haematological and biochemical parameters evaluated, only the number of neutrophils, lymphocytes, and creatinine concentration were changed at 800 mg/kg. Phytochemical profile of hydroethanolic extract of the xylopodium M. velame revealed the presence of phenolics and flavonoid compounds. The in vitro cytotoxicity assay result demonstrated that hydroethanolic extract of the xylopodium M. velame had no cytotoxic effects in Chinese hamster ovary cells. In the in vivo models, hydroethanolic extract of the xylopodium M. velame was shown to be relatively safe after sub-acute administration in rats which is relation to that the population daily takes a total dose of the plant xylopodium decoction or infusion about 23.29 times lower than the no-observed-adverse effect level dose in rats.

Dr. Enrique Suárez Hernández, egregio profesor del Instituto de Ciencias Básicas y Preclínicas "Victoria de Girón"

El Dr. Enrique Alberto Suárez Hernández matriculó en la Universidad de La Habana la carrera de Medicina en 1938 y se graduó en 1945. Ejerció como médico Municipal en Oriente, como médico forense en Banes, médico en Guanabacoa y profesor de Anatomía en la Escuela de Medicina de la Universidad de La Habana. En los años de la clandestinidad, colaboró con combatientes y campesinos que iban a verlo por problemas de salud. Al triunfo revolucionario se incorporó a las Milicias Nacionales Revolucionarias, fue fundador de los Comités de Defensa de la Revolución y miembro de la Central de trabajadores de Cuba. Participó en movilizaciones y trabajos voluntarios. Fundador del Instituto de Ciencias Básicas y Preclínicas "Victoria de Girón", Profesor Titular de Anatomía.

Dr. Enrique Alberto Suárez Hernández enrolled in the medical studies at the University of Havana in 1938 and graduated in 1945. He worked as Municipal Doctor in the East of Cuba, forensic doctor in the region of Banes, doctor in Guanabacoa, and Professor of Anatomy in the Medical School of the University of Havana. During the years of the clandestineness, he collaborated with combatants and farmers that went to see him with health problems. After the triumph of the Cuban Revolution, he became member of the National Revolutionary Militia. Dr. Enrique was one of the founders of the "Comités de Defensa de la Revolución" (CDR) and a member of the "Central de Trabajadores de Cuba" (CTC). He participated in mobilizations and voluntary works. Dr. Enrique Suárez Hernández was one of founders of the Institute of Basic and Pre-Clinical Sciences "Victoria de Girón"; full professor of Anatomy.

Minimum quality threshold in preclinical sepsis studies (MQTiPSS): quality threshold for fluid resuscitation and antimicrobial therapy endpoints / 中华危重病急救医学

As outlined in the International Guidelines for Management of Sepsis and Septic Shock: 2016, initial fluid resuscitation and administration of antibiotics are key steps in the early management of sepsis and septic shock. However, such clear guidelines do not exist for preclinical sepsis models. To address these shortcomings, the Wiggers-Bernard conference on preclinical sepsis models was held in Vienna in May 2017. The participants reviewed 260 of the most highly cited papers between 2003 and 2012 that used sepsis models. The review demonstrated that over 70% of experiments either did not use or failed to report resuscitation and/or antibiotic treatment. This information served as the basis to create a series of recommendations and considerations for preclinical sepsis models; this Part Ⅲ report details the recommendations for fluid resuscitation and antibiotic treatment that should be addressed in sepsis models. Similar to human sepsis, fluid resuscitation is recommended in the experimental setting unless part of the study. Iso-osmolar crystalloid solutions are preferred. The administration route and its timing should be adjusted to the specific requirements of the model with preference given to dynamic rather than static hemodynamic monitoring. Predefined endpoints for fluid resuscitation and avoidance of fluid overload should be considered. Preclinical sepsis studies display serious inconsistencies in the use of antimicrobial protocols. To remedy this, antimicrobials are recommended for preclinical studies, with choice and dose adjusted to the specific sepsis model and pathogen(s). Ideally, the administration of antimicrobials should closely mimic clinical practice, taking into account the drug's pharmacokinetic profile, alterations in absorption, distribution and clearance, and host factors such as age, weight, and comorbidities. These recommendations and considerations are proposed as "best practices" for animal models of sepsis that should be implemented.

Minimum quality threshold in preclinical sepsis studies (MQTiPSS): quality threshold for fluid resuscitation and antimicrobial therapy endpoints / 中华危重病急救医学

As outlined in the International Guidelines for Management of Sepsis and Septic Shock: 2016, initial fluid resuscitation and administration of antibiotics are key steps in the early management of sepsis and septic shock. However, such clear guidelines do not exist for preclinical sepsis models. To address these shortcomings, the Wiggers-Bernard conference on preclinical sepsis models was held in Vienna in May 2017. The participants reviewed 260 of the most highly cited papers between 2003 and 2012 that used sepsis models. The review demonstrated that over 70% of experiments either did not use or failed to report resuscitation and/or antibiotic treatment. This information served as the basis to create a series of recommendations and considerations for preclinical sepsis models; this Part Ⅲ report details the recommendations for fluid resuscitation and antibiotic treatment that should be addressed in sepsis models. Similar to human sepsis, fluid resuscitation is recommended in the experimental setting unless part of the study. Iso-osmolar crystalloid solutions are preferred. The administration route and its timing should be adjusted to the specific requirements of the model with preference given to dynamic rather than static hemodynamic monitoring. Predefined endpoints for fluid resuscitation and avoidance of fluid overload should be considered. Preclinical sepsis studies display serious inconsistencies in the use of antimicrobial protocols. To remedy this, antimicrobials are recommended for preclinical studies, with choice and dose adjusted to the specific sepsis model and pathogen(s). Ideally, the administration of antimicrobials should closely mimic clinical practice, taking into account the drug's pharmacokinetic profile, alterations in absorption, distribution and clearance, and host factors such as age, weight, and comorbidities. These recommendations and considerations are proposed as "best practices" for animal models of sepsis that should be implemented.

Evaluation of undergraduate dental students in typodont preparation for all-ceramic crowns

Background: All-ceramic crown (ACC) preparations are widely used in day-to-day dentalclinical practice. Objectives: This study aimed to evaluate all-ceramic crown preparationsperformed by pre-clinical dental students at the College of Dentistry, Jazan University inSaudi Arabia and to compare the quality of the preparations between male and female groups.Materials and Methods: A total of 95 ivory teeth were prepared by fourth-year dentalstudents (44 males, 51 females). The students prepared a maxillary right central incisor forACC after mounting in the Frasaco typodont arches. Two silicone putty indexes for maxillaryanterior were obtained that extended to cover one or two teeth on either side. The facial indexwas used to provide information about the facial reduction mesio-distally. Another index wasprepared by cutting the silicone in half along the faciolingual midline of the prepared tooth,providing us with incisal, buccal, palatal, and axial reductions, in addition to biplanereduction. The data were encoded into a Statistical Package for Social Sciences program andanalyzed accordingly using Chi-square test. Results: The preparations of ACC for maxillaryanterior teeth were acceptable, ranging within 60%-85% in all criteria, which includedstructural durability, retention, and resistance. The male group was more excellent in incisalreduction (41.0%), whereas the female group was more excellent in axial taper preparations(59.1%), resulting in significant differences between genders in this preparation criteria. Allgender groups showed acceptable tooth preparations in shoulder reductions and location offinish lines, ranging within 57%-89%. Conclusion: The preparations for ACC achieved bythese dental students were considered clinically acceptable. The students clearly understoodthe principles of crown preparation. However, they still require more practice in order tomaster the art of crown preparation.

Pre Clinical- Basic Sciences Teaching Curriculum Of A Medical School in A Developing Country -Are We Doing It Right.

Background: Preclinical teaching of basic sciences provides the basis for the development of clinical reasoning skills and the ability to make management decisions. However, many senior undergraduates, pre-interns and doctors indicate that basic sciences knowledge is poorly recalled and has little relevance to their clinical practice. Objectives: To explore the perceptions of medical students in their clinical years, and pre-interns about the basic sciences courses taught to them in the preclinical years, and to assess how each group rates the applicability of these courses to current clinical training. Methods: A descriptive cross-sectional study was conducted among 118 pre-interns and 146 undergraduate medical students using a self-administered questionnaire, regarding their perceptions on preclinical basic sciences teaching. For statistical analysis chi square test was applied. Results: More than 75% both pre-interns and undergraduates agreed that preclinical teaching was useful and relevant for future clinical work. 50-75% frequently revisited preclinical subjects despite unapparent clinical significance. 55% couldn’t remember most of preclinical content. Physiology was the most retained (76%) and most clinically relevant subject (80%). Majority of (>60%) both the groups suggested more teaching time and >75% suggested concurrent clinical exposure for preclinical teaching. Undergraduates and preinterns differed in that 56% of undergraduates and 37% of pre-interns had studied pre clinical subjects just to pass examinations (p<0.01).Conclusions: Majority of undergraduates and pre-interns felt that preclinical teaching is interesting and relevant for future clinical practice, though recall and clinical significance were suboptimal. Revising teaching methods with interdisciplinary integration, early clinical exposure showing relevance of basic sciences and allocating more teaching time utilizing clinicians should be considered.

Ensaio pré-clínico com desfibrilador externo / Pre-clinical trial with external defibrillator

OBJETIVOS: Avaliar a eficácia da desfibrilação em resposta à fibrilação ventricular induzida e descrever as mudanças macroscópicas ocorridas nos corações de suínos após choque de descarga capacitiva exponencial truncada aplicado por protótipo de desfibrilador produzido no Brasil e por um desfibrilador de referência, líder de mercado internacional.MÉTODOS: Dezesseis suínos foram agrupados em quatro grupos de quatro animais, para verificar a eficácia da desfibrilação em resposta à fibrilação ventricular induzida, aplicando cargas de 50 J e 100 J, assim como avaliar a segurança dos desfibriladores usados, através de análises macroscópicas da pele e do coração. Foram avaliados eritema, edema, bolhas, líquido na cavidade pericárdica, queimaduras e tecido carbonizado pós-choque.RESULTADOS: Todos os suínos, após um minuto da indução à fibrilação ventricular, desenvolveram taquicardia que progrediu à fibrilação ventricular. Quando utilizada baixa energia, o equipamento protótipo obteve 25% de sucesso com um suíno revertido, enquanto o equipamento referência obteve 50% de sucesso, com duas reversões. Entretanto, com energia a 100 J, o equipamento protótipo reestabeleceu o ritmo sinusal em três suínos (75%) e o equipamento referência realizou somente uma desfibrilação eficaz (25%). A aplicação de energia 100 J associou-se com queimadura cutânea de Grau II em apenas um suíno com o desfibrilador protótipo e em quatro suínos com o equipamento referência. As lesões do tecido cardíaco ocorreram em igual número com ambos os desfibriladores.CONCLUSÕES: O desfibrilador protótipo, quando aplicado com energia 100 J, demonstrou maior eficácia na reversão da fibrilação ventricular e apresentou menor injúria que o desfibrilador de referência com a mesma energia. Este estudo ajudará a elevar o padrão tecnológico e a ampliar a oferta qualificada de equipamentos para a saúde produzidos no Brasil, substituindo e/ou diminuindo importações e oferecendo um dispositivo seguro de última geração.

AIMS: To evaluate the efficacy of defibrillation in response to induced ventricular fibrillation and to describe the macroscopic changes in porcine hearts after truncated exponential capacitive discharge shock applied by a prototype defibrillator produced in Brazil and a reference, international market leader defibrillator.METHODS: Sixteen pigs were divided into four groups of four animals each, to verify the effectiveness of the defibrillator in response to induced ventricular fibrillation by applying loads of 50 J to 100 J, and assess the safety of the defibrillator by macroscopic analysis of the skin and heart. Erythema, edema, blistering, fluid in the pericardial cavity, burns, and post-shock charred tissue were evaluated.RESULTS: All pigs, after one minute of inducing ventricular fibrillation, developed tachycardia and progressed to ventricular fibrillation. When used low energy, the prototype equipment obtained 25% of success, with one reversed pig, while the reference equipment has obtained a success rate of 50%, with two reversals. However, with energy 100 J, the prototype equipment reestablished sinus rhythm in three pigs (75%) and the reference product only made effective defibrillation in one (25%). The application of 100 J energy was associated with skin burns Grade II in only one pig with the prototype defibrillator and four pigs with the reference equipment. The heart tissue injuries occurred in equal numbers with both defibrillators.CONCLUSIONS: The prototype defibrillator, when applied with 100 J energy, was more effective in reversing ventricular fibrillation and showed less injury than the reference defibrillator with the same energy. This study may help to raise the technological standard and to increase the supply of qualified health equipment produced in Brazil, replacing and/or decreasing imports and providing a secure next-generation device.

Pre-clinical toxicity & immunobiological evaluation of DNA rabies vaccine & combination rabies vaccine in rhesus monkeys (Macaca mulatta).

Background & objectives: Pre-clinical toxicology evaluation of biotechnology products is a challenge to the toxicologist. The present investigation is an attempt to evaluate the safety profile of the first indigenously developed recombinant DNA anti-rabies vaccine [DRV (100 μg)] and combination rabies vaccine [CRV (100 μg DRV and 1.25 IU of cell culture-derived inactivated rabies virus vaccine)], which are intended for clinical use by intramuscular route in Rhesus monkeys. Methods: As per the regulatory requirements, the study was designed for acute (single dose - 14 days), sub-chronic (repeat dose - 28 days) and chronic (intended clinical dose - 120 days) toxicity tests using three dose levels, viz. therapeutic, average (2x therapeutic dose) and highest dose (10 x therapeutic dose) exposure in monkeys. The selection of the model i.e. monkey was based on affinity and rapid higher antibody response during the efficacy studies. An attempt was made to evaluate all parameters which included physical, physiological, clinical, haematological and histopathological profiles of all target organs, as well as Tiers I, II, III immunotoxicity parameters. Results: In acute toxicity there was no mortality in spite of exposing the monkeys to 10XDRV. In sub chronic and chronic toxicity studies there were no abnormalities in physical, physiological, neurological, clinical parameters, after administration of test compound in intended and 10 times of clinical dosage schedule of DRV and CRV under the experimental conditions. Clinical chemistry, haematology, organ weights and histopathology studies were essentially unremarkable except the presence of residual DNA in femtogram level at site of injection in animal which received 10X DRV in chronic toxicity study. No Observational Adverse Effects Level (NOAEL) of DRV is 1000 ug/dose (10 times of therapeutic dose) if administered on 0, 4, 7, 14, 28th day. Interpretation & conclusions: The information generated by this study not only draws attention to the need for national and international regulatory agencies in formulating guidelines for pre-clinical safety evaluation of biotech products but also facilitates the development of biopharmaceuticals as safe potential therapeutic agents.

Attitude Survey of Pharmacy Students before and after Long-term Practical Training, and the Evaluation of Pre-clinical Training / 社会薬学

We conducted a questionnaire survey involving 270 interns in the year 2011 at the pharmaceutical department of Teikyo University, in order to clarify pre- to post-practical training changes in: 1) the degree of pre-clinical training’s usefulness, 2) desired workplace in the future, 3) degree of satisfaction, 4) confidence degree of practical training, etc. The degree of pre-clinical training’s usefulness exceeded 80% in all training periods. Regarding the desired workplace in the future, a large proportion of students answered that they want to become a pharmacist in a pharmacy or hospital, both before and after their practical training in all training periods. Also, it was estimated that students decide their career with reference to their practical training experience. In terms of the degree of satisfaction with practical training, the proportions of those who answered “Satisfied” or “Somewhat satisfied” were: 95.1% in the 1st, 95.6% in the 2nd, and 86.1% in the 3rd periods. The confidence degree significantly increased after practical training in all periods. Because the confidence degree showed a tendency to be higher before the 3rd period of training compared to the other two periods, it was considered that students’ experience of practical training led to increased confidence degree. Regarding communication abilities, the degrees of before-after confidence degree and pre-clinical training’s usefulness were low, and, hence, it was suggested that pre-clinical training needs to be further improved regarding these areas.

Anxiolytic and antidepressive effects of the homeopathic complex Homeo-pax® (pre-clinical study) / Anxiolytic and antidepressive effects of the homeopathic complex Homeo-pax® (pre-clinical study)

The homeopathic complex Homeo-Pax® has been used as an antidepressant and anxiolytic homeopathic medicine available in Brazil. It is a complex mixture prepared with Aconitum nap.6cH, Aurum met. 6cH, Phosphorus 6cH, Argentum nitricum 6cH, Arsenicum alb. 6cH, and Valeriana officinalis 3cH. This study had evaluated the behavior in rats after treatment with Homeo-Pax® in pre-clinical models of depression and anxiety. Elevated Plus Maze Test (EPM), Forced Swimming Test (FST), Open Field Test (OFT) and the Rota Rod Test (RRT) behavior assays were used to confirm its activity. In the EPM, the animals treated with Homeo-pax® on the 1st day and until the 20th day of treatment remained longer in the open arms of the maze than on 30th day. This result was statistically significant compared with the control group (p < 0.05). In the FST, the treatment with Homeo-pax® (0.5 ml, p.o) increased the swimming time, compared to the control group. This effect was dependent on treatment time, resulting in a similar effect to that presented by amfepramone (10 mg/kg, p.o). In the OFT, crossing by the animals was significantly increased by the treatment with amfepramone (10mg/kg, p.o), and also with the 30- day treatment with Homeo-pax® . In the RRT, the 30-day treatment with Homeo-pax® (0.5 ml, p.o) did not affect the animals? motor coordination, compared with the control group, which presented the same behavior. Based on the results obtained, it can be suggested that the homeopathic complex Homeo-pax® has anxiolytic and antidepressant properties without affecting motor coordination capacity.

O complexo homeopático Homeo-Pax® tem sido usado no Brasil como um medicamento homeopático de ação antidepressiva e ansiolítica. O Homeo-Pax® é um complexo preparado com Aconitum nap. 6cH, Aurum met. 6cH, Phosphorus 6cH, Argentum nitricum 6cH, Arsenicum alb. 6cH e Valeriana officinalis 3cH. Este estudo avaliou o comportamento de ratos após o tratamento com Homeo-Pax® em modelos pré-clínicos de depressão e ansiedade. Testes de labirinto em cruz elevado (EPM), nado forçado (FST), campo aberto (OFT) e Rotarod (RRT) foram usados para avaliar a atividade dos animais. No EPM, os animais tratados com Homeo-pax® permaneceram mais tempo nos braços abertos do labirinto, durante do 20 primeiros dias de tratamento, em relação ao 30º dia. Este resultado foi estatisticamente significativo quando comparado com o grupo controle (p < 0.05). No FST, o tratamento com Homeo-pax® (0.5 ml, p.o) aumentou o tempo de nado, comparado ao grupo controle. Este efeito foi dependente o tempo de tratamento, resultando similar ao efeito da amfepramona (10 mg/kg, p.o). No OFT, o movimento dos animais foi significativamente aumentado pelo tratamento com amfepramona (10mg/kg, p.o) e também no 30º dia de tratamento com Homeo-pax® . No RRT, o tratamento por 30 dias com Homeo-pax® (0.5 ml, p.o) não afetou a coordenação motora dos animais, em relação ao grupo controle. Baseado nesses resultados, pode ser sugerido que o complexo homoepático Homeo-pax® tem propriedades ansiolíticas e antidepressivas sem afetar a coordenação motora.

El complejo homeopático Homeo-pax® viene siendo usado en Brasil como un medicamento homeopático de acción antidepresiva y ansiolítica. El Homeo-pax® es un complejo preparado con Aconitum nap 6cH, Aurum Met 6cH, Phosphorus 6cH, Argentum Nitricum 6cH, Arsenicum Alb 6cH y Valeriana officinalis 3cH. Este estudio evaluó el comportamiento de camondongos después del tratamiento con Homeo-pax® en modelos preclinicos de depresión y ansiedad. Testes de laberinto en cruz elevado (EPM) nado forzado (FST), campo abierto (OFT) y Rotarod (RRT) fueron usados para evaluar la actividad de los animales. En el EPM los animales tratados com Homeo-pax® permanecieron mas tiempo en los brazos abiertos del laberinto durante los 20 primeros dias de tratamiento en relación al 30º dia. Este resultado fue estadísticamente significativo si comparado con el grupo control (p<0.05). En el FST, el tratamiento con Homeo-pax® (0.5 ml,p.o) aumentó el tiempo de nado, comparado al grupo control. Este efecto fue dependiente del tiempo de tratamiento, resultando similar al efecto de la anfepramona (10 mg/kg, p.o). En el OFT, el movimiento de los animales fue significativamente aumentado por el tratamiento con anfepramona (10mg/kg, p.o) y tambien en el 30º dia de tratamiento con Homeo-pax® . En el RRT el tratamiento por 30 dias con Homeo-pax® (0.5 ml, p.o) no afectó la coodinación motora de los animales, en relación al grupo control. Basado en esos resultados puede ser sugerido que el complejo homeopático Homeo-pax® tiene propiedades ansiolíticas y antidepresivas sin afectar la coordinación motora.