Rational drug repurposing for alzheimer's treatment using in-silico ligand and structure-based approaches

Abstract Alzheimer's disease is a devastating neurodegenerative disorder characterized by memory loss and cognitive decline. New AD treatments are essential, and drug repositioning is a promising approach. In this study, we combined ligand-based and structure-based approaches to identify potential candidates among FDA-approved drugs for AD treatment. We used the human acetylcholinesterase receptor structure (PDB ID: 4EY7) and applied Rapid Overlay of Chemical Structures and Swiss Similarity for ligand-based screening.Computational shape-based screening revealed 20 out of 760 FDA approved drugs with promising structural similarity to Donepezil, an AD treatment AChE inhibitor and query molecule. The screened hits were further analyzed using docking analysis with Autodock Vina and Schrodinger glide. Predicted binding affinities of hits to AChE receptor guided prioritization of potential drug candidates. Doxazosin, Oxypertine, Cyclopenthiazide, Mestranol, and Terazosin exhibited favorable properties in shape similarity, docking energy, and molecular dynamics stability.Molecular dynamics simulations confirmed the stability of the complexes over 100 ns. Binding free energy analysis using MM-GBSA indicated favourable binding energies for the selected drugs. ADME, formulation studies offered insights into therapeutic applications and predicted toxicity.This comprehensive computational approach identified potential FDA-approved drugs (especially Doxazosin) as candidates for repurposing in AD treatment, warranting further investigation and clinical assessment.

Effect of the percentage of Bos taurus inheritance on the fertility of Holstein×Zebu and Brown Swiss×Zebu cows in the Mexican tropics

Background: No dairy breed or crossbreed has superior overall performance in all environments; therefore, it is necessary to determine which crossbreed is the most suitable for the Mexican tropic and what proportion of European breed is optimum for reproduction. Objective: To assess the effect of the proportion of Bos taurus (Bt) genes on reproductive performance of Holstein×Zebu (HZ) and Brown Swiss×Zebu (BZ) cows, and compare reproductive performance of these genotypes in a dual- purpose production system. Methods: Cows were maintained in a rotational grazing system on African star grass (Cynodon plectostachyus) in Veracruz, Mexico. Cows were milked twice daily. Calves were kept tied to the side of their dams while the cows were milked. Results: The percentage of Bt genes did not affect (p>0.05) fertility traits (age at first calving, days to first service after calving, services per conception, conception rate at first service, days open until conception, gestation length, and calving interval) of BZ cows. In contrast, HZ cows with less than 75% Holstein (H) genes were 0.3 years younger (p<0.05) at first calving and had 39.8 fewer days open (p<0.05) than HZ cows with 75% H genes or more. In addition, the calving interval of HZ cows with less than 75% H genes was 44.8 days shorter (p<0.05) than that of HZ cows with 75% H genes or more. The HZ cows had five fewer days pregnant and were 22.8 kg heavier at calving (p<0.05) than BZ cows. Conclusions: The effect of the percentage of Bt genes on cow fertility depends on the dairy breed used. In general, BZ and HZ cows present similar reproductive performance.

Antecedentes: Ninguna raza lechera o cruce tiene un desempeño general superior en todos los ambientes; por lo tanto, es necesario determinar cuál cruce lechero es más apropiado en el trópico mexicano y qué proporción de raza europea es óptima para la reproducción. Objetivo: Evaluar el efecto de la proporción de genes Bos taurus (Bt) en el desempeño reproductivo de vacas cruzadas Holstein×Cebú (HC) y Pardo Suizo×Cebú (PC), y comparar el desempeño reproductivo de estos dos genotipos en un sistema de producción doble propósito. Métodos: Las vacas se mantuvieron en un sistema de pastoreo rotacional en zacate Estrella de África (Cynodon plectostachyus) en Veracruz, México. Las vacas se ordeñaron dos veces al día. Los becerros se mantuvieron atados, a un costado de sus madres mientras éstas se ordeñaron. Resultados: El porcentaje de genes Bt no afectó (p>0,05) ninguna característica de fertilidad (edad a primer parto, días a primer servicio después del parto, servicios por concepción, tasa de preñez a primer servicio, días abiertos a la concepción, duración de la gestación, e intervalo entre partos) de las vacas PC. En contraste, las vacas HC con menos de 75% de genes Holstein (H) fueron 0,3 años más jóvenes (p<0,05) al primer parto y tuvieron 39,8 días abiertos menos (p<0,05) que las vacas HC con 75% de genes H o más. Además, el intervalo entre partos de las vacas HC con menos de 75% de genes H fue 44,8 días más corto (p<0,05) que el de las vacas HC con 75% de genes H o más. Las vacas HC tuvieron cinco días de gestación menos y fueron 22,8 kg más pesadas al parto (p<0,05) que las PC. Conclusiones: El efecto del porcentaje de genes Bt sobre la fertilidad de la vaca depende de la raza lechera usada. En general, las vacas PC y HC tienen similar desempeño reproductivo.

Antecedentes: Nenhuma raça ou cruza leiteira tem desempenho geral superior em todos os ambientes; portanto, é necessário determinar qual cruza leiteira é mais apropriada no trópico mexicano e qual proporção da raça europeia é ideal para a reprodução das vacas. Objetivo: Avaliar o efeito da proporção de genes Bos taurus (Bt) no desempenho reprodutivo de vacas Holandês×Zebu (HZ) e Pardo Suíço×Zebu (PZ), e comparar o desempenho reprodutivo desses dois genótipos em sistema de produção de dupla aptidão. Métodos: As vacas foram mantidas em sistema de pastoreio rotacional em capim Estrela de África (Cynodon plectostachyus) em Veracruz, México. As vacas foram ordenhadas duas vezes por dia. Os bezerros foram mantidos ao lado de suas mães enquanto eram ordenhadas. Resultados: A porcentagem dos genes Bt não afetou (p>0,05) nenhuma característica de fertilidade (idade ao primeiro parto, número de dias para o primeiro serviço pós-parto, serviços por concepção, taxa de prenhes no primeiro serviço, dias abertos, período de gestação e intervalo entre partos) das vacas PZ. Em contraste, vacas HC com menos de 75% dos genes Holandês (H) eram 0,3 anos mais jovens (p<0,05) no primeiro parto e tiveram 39,8 dias abertos a menos (p<0,05) do que as vacas HZ com 75% ou mais dos genes H. Além disso, o intervalo de parto das vacas HZ com menos de 75% dos genes H foram 44,8 dias mais curtos (p<0,05) do que as vacas HZ com 75% ou mais de genes H. As vacas HZ tiveram cinco dias de gestação a menos e foram 22,8 kg mais pesadas no parto (p<0,05) do que as PZ. Conclusões: O efeito da porcentagem de genes Bt na fertilidade da vaca dependeu da raça leiteira utilizada. Em geral, as vacas PZ e HZ tiveram desempenho reprodutivo semelhante.

Reverse Swiss Roll technique for diabetic vitreous membranes

Background: Diabetic membranes are always a challenge for a surgeon because of sticky nature and chances of iatrogenic break while removing. Purpose: To demonstrate a safe reverse swiss roll technique to dissect diabetic vitreous membranes. Synposis: Approaches and techniques for membrane dissection are segmentation, delamination and en-bloc dissection using various types of instruments and illumination. With vitreous cutte, picks and scissors, surgical steps are traditionallu performed by using classic lift and shave technique. After identifying the plane, tissue is lifted and then cut, which puts the retina at risk of break because of traction and active suction. Such a threat can be reduced by placing the cutter above the membrane thereby having the membrane itseld acting as a protective cushion to the retina. Port here, unlike lift and shave technique, doesn抰 face the edge of membrane but is exactly 180 degree opposite and membrane curls into port because of suction. Also, hemostasis is maintained by continuous aspiration and cutting as the instrument is moved side to side, retracting from the edge. Highlights: Reverse swiss roll technique is safer compared to lift and shave because of the safety cushion of the membrane between the port and the retina. There is inherently less chances of retinal break because the active suction from the port is directed away from the retina. The technique also minimises traction and localised pull on the atrophic macula

Overview of protein posttranslational modifications in Arthropoda venoms

Accidents with venomous animals are a public health issue worldwide. Among the species involved in these accidents are scorpions, spiders, bees, wasps, and other members of the phylum Arthropoda. The knowledge of the function of proteins present in these venoms is important to guide diagnosis, therapeutics, besides being a source of a large variety of biotechnological active molecules. Although our understanding about the characteristics and function of arthropod venoms has been evolving in the last decades, a major aspect crucial for the function of these proteins remains poorly studied, the posttranslational modifications (PTMs). Comprehension of such modifications can contribute to better understanding the basis of envenomation, leading to improvements in the specificities of potential therapeutic toxins. Therefore, in this review, we bring to light protein/toxin PTMs in arthropod venoms by accessing the information present in the UniProtKB/Swiss-Prot database, including experimental and putative inferences. Then, we concentrate our discussion on the current knowledge on protein phosphorylation and glycosylation, highlighting the potential functionality of these modifications in arthropod venom. We also briefly describe general approaches to study "PTM-functional-venomics", herein referred to the integration of PTM-venomics with a functional investigation of PTM impact on venom biology. Furthermore, we discuss the bottlenecks in toxinology studies covering PTM investigation. In conclusion, through the mining of PTMs in arthropod venoms, we observed a large gap in this field that limits our understanding on the biology of these venoms, affecting the diagnosis and therapeutics development. Hence, we encourage community efforts to draw attention to a better understanding of PTM in arthropod venom toxins.(AU)

Modeling and validation of L-asparaginase enzyme, an anticancer agent using the tools of computational biology

Background: The L-Asparaginase is a medically important drug. The L-Asparaginase enzyme, an anticancer agent produced by microorganisms is used for the treatment of patients suffering from lymphoma and leukemia. The L-Asparaginase is economical and its administration is easy when compared to other commercial drugs available in market. Many microbes have been reported to produce the L-Asparaginase.Methods: In the present work the sequence of L-Asparaginase enzyme protein was obtained from the Universal Protein Resource (UNIPROT) server. The sequence of L-Asparaginase was used to generate 3-D model of L-Asparaginase in SWISS MODEL server. The constructed L-Asparaginase model was verified using Ramachandran Plot in PROCHECK server.Results: The FASTA format of L-Asparaginase enzyme of Bacillus subtilis strain 168 was retrieved from UNIPROT server. The FASTA format of L-Asparaginase was submitted to SWISS MODEL and its three-dimensional structural model was developed based on relevant template model. The model structure of L-Asparaginase was validated in PROCHECK server using Ramachandran Plot. The Ramachandran Plot of L-Asparaginase model inferred the reliability of L-Asparaginase structure model developed in SWISS MODEL server.  Conclusions: In the present study computational tools were exploited to develop and validate a potent anticancer drug, L-Asparaginase. Further the modeled L-Asparaginase enzyme protein can be improved using advanced bioinformatics tools and the same improved enzyme can be produced by improving the L-Asparaginase producing microbial strains by site-directed mutagenesis in the corresponding gene.

Biomechanical characteristics on ball games for male youth with different body mass index based on anybody simulation and electromyogram test / 中国组织工程研究

BACKGROUND: Anybody’s musculoskeletal modeling system simulates the relationship between human skeleton, muscle and environment by using mathematical modeling technology. It can study the reverse dynamics of human body and obtain the maximum muscle strength of three lower limb joints. OBJECTIVE: To study the lower extremity muscle strength values of 24 male college students with different body mass indexes in one cycle of sitting Swiss ball, and to compare the mean root-mean-square of the subjects in sitting Swiss ball and bench. METHODS: Twenty-four male college students were divided into normal group, overweight group and obesity group according to body mass index. BTS 3D infrared motion capture system, Kistler 3D dynamometer and BTS surface electromyography system were used to record the dynamic and electromyographic parameters simultaneously. The differences in muscle force and electromyographic parameters between different groups were qualitatively compared by one-way analysis of variance, and the mean differences were compared by quantitative difference analysis. RESULTS AND CONCLUSION:(1) In terms of muscle strength, from sitting to standing, compared with the obese group, the normal group showed significant differences in rectus femoris, semimememial muscle, biceps femoris longhead, popliteal muscle, soleus muscle and tibial anterior muscle (P < 0.05, 0.47 ≤ QD < 0.80), and the quadratus femoris muscle and pectineus muscle showed significant differences (P < 0.01, QD ≥ 0.80). There was a significant difference in muscle strength of quadratus femoris between the obese group and the overweight group (P < 0.05, 0.47 ≤ QD < 0.80). From standing to sitting, there were significant differences in muscle strength of sartorus, extensor pollicis, and gastrocneum between the normal group and the obese group (P< 0.05, 0.47 ≤ QD < 0.80). (2) In terms of root-mean-square electromyogram value, from sitting to standing, the biceps femoris and gastrocnastus muscles in the normal group were significantly different from those in the obese group (P < 0.05, 0.47 ≤  QD < 0.80); from standing to sitting, rectus femoris muscles in the normal group were significantly different from those in the obese group (P < 0.05,  0.47 ≤ QD < 0.80). In the Swiss ball sitting state, from sitting to standing, the tibial anterior muscle and biceps femoris were significantly different between the normal group and the obese group (P < 0.05, 0.47 ≤ QD < 0.80). From standing to sitting, the electromyogram values of gastrocnemius muscle and right erector spine muscle were significantly different between the normal group and the obese group (P < 0.05, 0.47 ≤ QD < 0.80). These findings indicated that (1) In each group of BMI, the dominant muscle generation from sitting to sitting was gluteus medius muscle, vastus lateralis muscle, biceps longus muscle, rectus femoris muscle, gastrocnemius muscle, tibia anterior muscle and soleus muscle; and from standing to sitting, gluteus medius muscle, vastus lateralis muscle, biceps longus muscle, gastrocnemius muscle, tibia anterior muscle and soleus muscle. (2) Compared with the sitting stool, the subjects had higher root-mean-square of tibial anterior muscle, rectus femoris muscle, biceps femoris muscle and gastrocnemius muscle when sitting Swiss ball.

Wide range of F cell levels in healthy Thai adults: Influence of Swiss-type hereditary persistence of foetal haemoglobin & ?-haemoglobinopathy

Background & objectives: Swiss-type hereditary persistence of foetal haemoglobin (HPFH) has been shown to be responsible for the wide range of F cell levels in healthy Thai adults. However, a survey for F cells in healthy Thai adults has not been performed. This study was conducted to determine the F cell distribution in adult Thai blood donors and to assess the possible involvement of ?-thalassaemia and haemoglobin E (HbE) carriers in increased HbF levels. Methods: Thai blood donors (n=375, 205 males and 170 females) were included in the study. Blood samples were collected for measuring haemoglobin (Hb) concentration and haematocrit (Hct) and F cell levels. Hb and Hct levels were determined by automated blood counter, while F cells were quantified by flow cytometric analysis of F cells stained by fluorescein isothiocyanate-conjugated anti ?-globin monoclonal antibody. Finally, F cell levels were compared between blood samples having mean corpuscular volume (MCV ) <80 fl and ?80 fl as well as between ?-haemoglobinopathies (HbE and ?-thalassaemia carriers) and normal adults. Results: F cell levels varied markedly spanning 0.80-39.2 per cent with a positively skewed distribution. Thirty two per cent of these individuals had F cell levels more than the 4.5 per cent cut-off point. F cell levels in females were significantly higher than those in males (P<0.05). F cell levels in individuals having MCV <80 fl were significantly higher than those having MCV ?80 fl (P<0.05). ?-haemoglobinopathy (HbE and ?-thalassaemia carriers) had significantly higher F cell levels than normal individuals (P<0.05). Interpretation & conclusions: The present results showed that besides Swiss-type HPFH, the ?-haemoglobinopathy was expected to be involved in increased F cell levels in adult Thais. Thus, influence of ?-haemoglobinopathy must be considered in interpreting F cell levels in area endemic of this globin disorder.

Phytochemical Analysis and Antiplasmodial (curative) Activities of Methanolic Leaf Extract of Morinda lucida (Ewe Oruwo) in Male Swiss Mice Infected with Plasmodium berghei NK65

Aim:Medicinal plants have been used for the treatment of many infections and diseases including malaria. The study was conducted to determine the effect of in vivoanti-plasmodialand antioxidant properties of the methanolic leaf extract of Morinda lucidain male Swiss albino mice infected with Plasmodium Berghei NK65. Study Design and Methodology:Phytochemical, GC-MS and AAS analyses were determined in the plant. Swiss albino mice were inoculated intraperitoneally with Plasmodium bergheiNK65. Thirty-five (35) mice were grouped into seven groups, five per group. Group A were not infected with P.bergheiNK65.Group B, C and D served as the negative and positive control groups while Group E, F and G mice were treated with 400, 600 and 800 mg/kg body weight of methanolic leaf extract of M. lucida. Haematological parameters were determined in the whole blood using BC-3200 Auto Hematology Analyzer. TP, MDA, CAT, SOD % inhibition, SOD unit and vitamin A were all determined in the liver homogenateusing standard procedures.Results:The GC-MS result of the M. lucidashows the presence of five bioactive compounds. It was also observed that the plant contains the following minerals: iron, magnesium, potassium, phosphorus and copper. Acute toxicity shows that the LD50>000mg/Kg b.wt. The extract caused 30.96%, 32.93% and 67.23% reduction in parasitemia at 400, 600 and 800 mg/kg body weight respectively while chloroquine exerted 96.53% and artesunate exerted 92.03% reduction at 10 mg/kg body weight respectively. The Haematological parameters showed that the plant extractis nothaematotoxic since it significantly (P<0.05) reduced WBC count, and increase RBC, HGB, and HCT values in the treated mice compared to the infected untreated mice. This study shows that the mean lipid peroxidation (MDA) level was significantly decreased in the malaria treated mice (group C, D, E, F and G) compared to the untreated mice (group B). There was also a significant increase in the total protein, catalase, SOD % inhibition, SOD unit and Vitamin A levels in the liver homogenate of animals treated with chloroquine, artesunate and extract of M. lucidacompared to the untreated mice. Conclusions: The study shows that Morinda lucidapossess antiplasmodial activity in male Swiss mice infected with Plasmodium berghei NK 65.

The Effects Of Lumbar Stabilization Exercises On A Swiss Ball In Patients With Mechanical Low Back Pain

Background: Mechanical low back pain is one of the most common causes of discomfort amongst people all over. There are various exercises to reduce low back pain. Swiss ball exercises are one of the dynamic exercises which increase muscle strength, endurance, balance, and flexibility of the trunk while the individual leans on a swiss ball. Therefore the purpose of this study was to check the effects of lumbar stabilization exercises on a swiss ball in patients with mechanical low back pain. Methods: Forty participants out of which 30 were females and 10 were males who were suffering from mechanical low back pain between the age group of 20 to 60 years were included. They were divided into two groups, with each group having 20 subjects. One group was taught floor exercises, and the other was taught swiss ball exercises for two weeks thrice a week,i.e., six days. The pain and disability were checked with the Numeric Rating Scale, and Roland Morris Questionnaire scores respectively pre and post-intervention. Results: On comparison of the difference between both the groups the mean difference in the NRS and RMQ scores for floor group was one ± 1 and 0.75 ± 1.6(p<0.05). The mean difference in the NRS and RMQ scores for swiss ball group was 2.6 ± 0.5 and 3.7 ± 1.26(p<0.05). Conclusion: We can conclude that lumbar stabilization exercises on a swiss ball are effective in reducing mechanical low back pain compared to exercises done on the static surface.

Preclinical evaluation of antidepressant activity of aqueous extract of Piper betle leaves in Swiss albino mice

Background: There is a growing demand for alternative medicines derived from indigenous plants having natural antioxidants and neuroprotective actions for the treatment of many behavioural disorders such as anxiety and depression. This study was designed to screen antidepressant activity of aqueous extract of Piper betle L. leaf (betel leaf) in Swiss albino mice.Methods: Swiss albino mice of both sexes weighing 25-30grams were used in the present study. Piper betle leaves aqueous extract (PBAE) was administered to the animals at a dose of 100, 200mg/kg body weight orally for 14 days. On the 14th day, after 1 hour of PBAE administration, experiments on force swim test (FST) and tail suspension (TST) were carried out for studying the level of depression. In FST and TST, time of immobility was noted for a period of 5 minutes.Results: Data was analyzed by one-way ANOVA followed by Tukey Kramer’s multiple comparison test at P = 0.05. The results were represented as Mean±SE. PBAE at a dose of 100mg/kg has shown significant antidepressant activity, as evidenced by decrease in the immobility time in both the screening tests of depression.Conclusions: Present results demonstrated that PBAE possess potent antidepressant property. The exact mechanism(s) related to the active compound(s) in Piper betle leaf extract have to be elucidated in future studies.

In vivo antiplasmodial potential of three herbal methanolic extracts in mice infected with Plasmodium berghei NK65 / 中草药·英文版

Objective: The present study deals with the investigation of antiplasmodial potential of leaf methanolic extract of Aegle marmelos, Aristolochia indica and Cassia auriculata against Plasmodium berghei (NK65) infected mice. Methods: The chloroquine-sensitive parasites P. berghei (1 × 106) were inoculated into Swiss albino mice intraperitoneally. The methanol extracts of three herbal plants were orally administered in P. berghei infected mice which were further assessed using the four-day suppressive test at different doses of 150, 300 and 600 mg/kg per day. Chloroquine (CQ) was used as the standard drug with of 1.25, 2.5 and 5 mg/kg concentrations and was orally administered. Results: The leaves of A. marmelos, A. indica, and C. auriculata were found to suppress P. berghei parasitaemia in Swiss albino mice by (67.0 ± 4.02)%, (72.0 ± 8.44)% and (52.7 ± 2.06)% at 600 mg/kg/d with ED50 values of 284.73, 233.77 and 562.48 mg/kg, respectively. These herbal plants increased the mean survival time of infected mice and prevented body weight loss. GC-MS analysis revealed the presence of hentriacontan-16-one (C31H62O) in A. indica extract. The histopathology study showed non-toxic to kidney and liver at 600 mg/kg/body weight. Conclusions: Overall results revealed that herbal plants may be active in the development of novel and cheap antimalarial compounds.

The antipsychotic activity of alcoholic extract of Withania coagulans fruits in Swiss albino mice

Background: Schizophrenia is one of the most distressing central nervous system (CNS) disorders. It is described by positive, negative and cognitive symptoms. These symptoms can be controlled by the antipsychotic medicines. The numerous antipsychotic medications used today are not lacking the adverse drug reactions. The Withania coagulans a susceptible species, is not explored much for its CNS effects except in late seventies. Therefore, it was thought worthwhile to investigate anti-psychotic activities of alcoholic extract of Withania coagulans fruits. The objective of the present study was to assess the antipsychotic activity of alcoholic extract of Withania coagulans fruits in Swiss albino mice by Cook’s Pole Climb Apparatus for conditioned avoidance response (CAR)Methods: Cook’s Pole Climb Apparatus for conditioned avoidance response was used for assessing the antipsychotic activity of the alcoholic extract of 200mg/kg, 500mg/kg and 1000mg/kg doses of Withania coagulans fruits.Results: There was statistically (p-value >0.05) no significant association between any of the 200mg/kg, 500mg/kg and 1000mg/kg doses of the alcoholic extracts of Withania coagulans fruits with antipsychotic activity in Swiss albino mice.Conclusions: Withania coagulans fruits alcoholic extract did not demonstrate antipsychotic activity in Swiss albino mice under standard conditions.

Standardization of ethanol addiction model in Swiss albino Mice

Background: Addiction is compulsive need for use of a habit-forming substance. World Health Organization (WHO) reported that worldwide 3.3 million people died due to alcohol addiction in 2012-13 and 11% of the population in India indulged in heavy drinking in 2014. Addiction is a prime socio-economical problem of society. Studying alcohol dependence in humans involved many ethical issues and experimental difficulties. Hence nonhuman animal experimental model has been used for a research on the topic of alcohol intoxication and dependence. Ethanol dependence has been preferred to develop in genetically modified strain of mice, C-57 which has a natural inclination to consume and develop addiction. But studying addiction in this special strain requires top end experimental facilities and financial aids. Authors reported the animal model to study ethanol dependence in Swiss albino mice. Aim of the study was to develop ‘Ethanol Dependence in Swiss albino mice animal model’ by intermitted access of 20% ethanol.Methods: Dependence was developed in Swiss albino mice by intermitted access of 20% ethanol in two groups having six animals in each group. Dependence was confirmed by presence of the withdrawal symptoms like anxiety, muscular incoordination and behavioral changes of animals on abstinence of ethanol.Results: Significant difference was noted on withdrawal symptoms, i.e. anxiety, muscular coordination, muscle spasm and other behavior related to withdrawal.Conclusions: Ethanol dependence can be successfully developed in Swiss albino mice in 14 days.

Swiss ball exercises improve muscle strength and walking performance in ankylosing spondylitis: a randomized controlled trial / Exercícios na bola suíça melhoram a força muscular e o desempenho na caminhada na espondilite anquilosante: estudo clínico, controlado e randomizado

ABSTRACT Objective: The purpose was to evaluate the effectiveness of a progressive muscle strengthening program using a Swiss ball for AS patients. Methods: Sixty patients with AS were randomized into the intervention group (IG) or the control group (CG). Eight exercises were performed by the IG patients with free weights on a Swiss ball two times per week for 16 weeks. The evaluations were performed by a blinded evaluator at baseline and after 4, 8, 12 and 16 weeks using the following instruments: the one-repetition maximum test (1 RM), BASMI, BASFI, HAQ-S, SF-36, 6-minute walk test, time up and go test, BASDAI, ASDAS, ESR and CRP dosage and Likert scale. Results: There was a statistical difference between groups for: strength (1 RM capacity) in the following exercises: abdominal, rowing, squat, triceps and reverse fly (p < 0.005); 6-minute walk test (p < 0.001); timed up and go test (p = 0.025) and Likert scale (p < 0.001), all of them with better results for the IG. No differences were observed between the groups with respect to the functional capacity evaluation using the BASFI, HAQ-S, BASMI, SF-36, TUG, ASDAS, ESR and CPR dosage. Conclusions: Progressive muscle strengthening using a Swiss ball is effective for improving muscle strength and walking performance in patients with AS.

RESUMO Objetivo: Avaliar a efetividade de um programa de fortalecimento muscular progressivo com o uso de uma bola suíça em pacientes com espondilite anquilosante (EA). Métodos: Sessenta pacientes com EA foram randomizados em grupo intervenção (GI) ou grupo controle (GC). Os pacientes com EA fizeram oito exercícios com pesos livres em uma bola suíça duas vezes por semana durante 16 semanas. As avaliações foram feitas por um avaliador cego no início do estudo e após quatro, oito, 12 e 16 semanas com os seguintes instrumentos: teste de uma repetição máxima (1 RM), Basmi, Basfi, HAQ-S, SF-36, teste de caminhada de seis minutos, Timed up and go test, Basdai, Asdas, dosagem de VHS e PCR e escala de Likert. Resultados: Houve uma diferença estatisticamente significativa entre os grupos em relação à força (capacidade no teste de 1 RM) nos seguintes exercícios: abdominal, remada, agachamento, tríceps e crucifixo invertido (p < 0,005); teste de caminhada de seis minutos (p < 0,001); Timed up and go test (p = 0,025); e escala de Likert (p < 0,001), todos com melhores resultados no GI. Não foram observadas diferenças entre os grupos em relação à avaliação da capacidade funcional com Basfi, HAQ-S, Basmi, SF-36, TUG, Asdas, VHS e dosagem de PCR. Conclusões: O fortalecimento muscular progressivo com uma bola suíça é efetivo em melhorar a força muscular e o desempenho na caminhada em pacientes com EA.

In vivo study of pomegranate (Punica granatum) peel extract efficacy against Giardia lamblia in infected experimental mice

Objective: To investigate the efficacy of pomegranate (Punica granatum) peel extract as an alternative treatment on the white laboratory mice against giardiasis. Methods: Experimental animals were divided into five groups, including Group A:control (infected untreated), Group B: infected and fed with pectin 7 days before infection, Group C: infected and fed with pectin starting from 7th day of infection, Group D:infected and fed with pomegranate peel extract 7 days before infection, and Group E: infected and fed with pomegranate peel extract starting from 7th day of infection. Results: Results from this study revealed that the prevention rate in the experimental groups reached approximately 50%by the 10th day of using pomegranate peel extract. Moreover, stool cyst counts of groups showed a significant reduction in the shedding of cysts approximately 75.6%by day 20 post-infection. ELISA test showed a reduction in Giardia antigen in the stools of the experimental groups which received pomegranate peel extract. The cure rate of these groups was approximately 97.4% by 28th day of infection. Conclusions: Our present findings indicated that the pomegranate peel extract proved to be valuable in prevention and treatment of Giardia lamblia infection. Further studies are required to determine the effective dose of pomegranate peel extract against Giardia lamblia infection.

Faciliated primary culture and amplification of breast cancer cells and their biological properties / 基础医学与临床

Objective To efficiently builds up and expand breast cancer cells from cancer tissue and to identify their biological properties , provide abundant materials for research and personalized medicine .Methods Feeder cell layer and ROCK inhibitor Y-27632 were employed to faciliate the breast cancer cells;CCK-8 was used to determine the proliferation of the breast cancer cells; Cell cycle distribution was analyzed by flow cytometry; Histochemistry ( FH) assay to show the expression level of CK .The mRNA expression of HER-2, ER, PR and the breast cancer stem cell associated molecules (such as CD44, CD24, etc.) were detected by RT-PCR;STR assay was used for identifying verification of the cells .Results The use of feeder cells and Y-27632 facilitates rapid expand of the original breast cancer cells , and the cells have kept the original features of the tumor .Conclusions To use the method could obtain a large number of cells within a short time , which can promptly be used for the research of per-sonalized medicine .

Development status of traditional Chinese medicine today in Switzerland / 国际中医中药杂志

Global market shows gaint needs of traditional Chinese medicine (TCM) today. Switzerland is the pioneer and has a wide TCM market. The paper anaylses the local diseases, TCM therapies, the difficulties of MediQi TCM clinic and certificates of TCM clinics in Switzerland, in order to get a general image of TCM situation of Swtierzland today. It coucluds that TCM is well accepted in Switzerland and has marketing needs and the better way to push TCM service trade is to respect local economic regulation and cultural capability.

In vivo study of pomegranate (Punica granatum) peel extract efficacy against Giardia lamblia in infected experimental mice

Objective To investigate the efficacy of pomegranate (Punica granatum) peel extract as an alternative treatment on the white laboratory mice against giardiasis. Methods Experimental animals were divided into five groups, including Group A: control (infected untreated), Group B: infected and fed with pectin 7 days before infection, Group C: infected and fed with pectin starting from 7th day of infection, Group D: infected and fed with pomegranate peel extract 7 days before infection, and Group E: infected and fed with pomegranate peel extract starting from 7th day of infection. Results Results from this study revealed that the prevention rate in the experimental groups reached approximately 50% by the 10th day of using pomegranate peel extract. Moreover, stool cyst counts of groups showed a significant reduction in the shedding of cysts approximately 75.6% by day 20 post-infection. ELISA test showed a reduction in Giardia antigen in the stools of the experimental groups which received pomegranate peel extract. The cure rate of these groups was approximately 97.4% by 28th day of infection. Conclusions Our present findings indicated that the pomegranate peel extract proved to be valuable in prevention and treatment of Giardia lamblia infection. Further studies are required to determine the effective dose of pomegranate peel extract against Giardia lamblia infection.

Trunk exercise using the Swiss ball improves the functional balance and walking of stroke patients in the early stages of recovery / 中华物理医学与康复杂志

Objective To examine the effects of trunk exercises performed using a Swiss ball on functional balance and walking in the early stage of recovering from a stroke.Metbods Sixty hemiplegic stroke patients were randomly assigned to a control group or an experimental group,each of 30.Both groups were treated with routine physical training.Those in the control group did conventional trunk exercises,while the patients in the experimental group were given trunk exercises performed using a Swiss ball.The trunk control test (TCT) and the Berg Balance Scale (BBS) were used to assess the patients' trunk and balance function.Gait and balance function training and assessment apparatus (model AL-080) was used to measure and compare the scope of movement of the patient's center of pressure in static sitting over 30 seconds (LOM),the limits of stability (LOS),velocities and a gait asymmetry index (GAI).Results Significant improvements in TCT,BBS,LOM and LOS were observed in both groups after the training,but all of the measures improved significantly more in the experimental group than in the control group.Conclusions Swiss ball trunk exercise can obviously improve the trunk control,functional balance and walking of stroke patients in the early stages of recovery.

Estudo da alteração do esvaziamento gástrico em roedores

Fatores que alteram os níveis plasmáticos de substâncias químicas e, por conseguinte, modificam a sua cinética, como por exemplo, a gravidez, podem ter impactos sobre a segurança e eficácia de medicamentos. Em estudo recente, realizado por Carmo (2015), no Laboratório de Toxicologia Ambiental do Departamento de Biologia da Escola Nacional de Saúde Pública da Fundação Oswaldo Cruz (ENSP/FIOCRUZ), foi observado que a concentração plasmática do antimalárico difosfato de primaquina em camundongos fêmeas grávidas DBA/2 era menor do que a concentração do fármaco registrada em igual intervalo de tempo pós-adminstração em camundongos fêmeas não grávidas. Vários estudos sugerem que a diminuição da concentração plasmática de fármacos na gestante pode se dever a um retardo no esvaziamento gástrico e/ou um aumento no volume de distribuição. Alterações do trânsito no trato gastrintestinal podem influenciar diretamente a absorção de fármacos, resultando em absorção mais rápida ou mais lenta. O fármaco analgésico e antipirético paracetamol é absorvido quase que exclusivamente no intestino. Assim a velocidade da sua absorção depende do tempo de esvaziamento gástrico. Fatores tais como alimentação, idade, gravidez e/ou o uso de fármacos que promovem aceleração (metoclopramida) ou o retardo (morfina) da motilidade gastrointestinal, podem influenciar em sua absorção. O objetivo desse trabalho foi desenvolver e padronizar uma metodologia de análise do paracetamol que permitisse investigar o efeito da gravidez sobre o esvaziamento gástrico sobre a cinética de fármacos administrados em pequenos roedores. O método empregado para determinar as concentrações plasmáticas de paracetamol foi a cromatografia em fase líquida de alta eficiência com detector por arranjo de diodos e visualização no ultravioleta (CLAE-DAD-UV), em equipamento Shimadzu Class-VP...

Factors that affect plasma levels of chemicals, and consequently their kinetics, such as pregnancy, can impact on the safety and efficacy of medicines. In a recent study, conducted by Carmo (2015) at the laboratory of Environmental Toxicology (Department of Biological Sciences, National School Public Health, Oswaldo Cruz Foundation -ENSP / FIOCRUZ), it was shown that plasma concentrations of the anti-malarial drug primaquine diphosphate in pregnant female DBA/2 mice were lower than levels found in non pregnant female mice. During pregnancy a delayed gastric emptying and/or an increased volume of distribution may result in lower drug plasma concentrations. Pregnancy-produced changes in the gastrointestinal transit may influence drug absorption. Depending on whether gastric emptying is accelerated or slowed and on the place where drug absorption takes place (stomach or intestines) absorption can be accelerated or slowed. Paracetamol, an analgesic and antipyretic drug, is absorbed almost exclusively in the intestines and is used to investigate the effects of treatment on the gastric emptying rate. Factors such as diet, age, pregnancy or the administration of drugs which accelerate (metoclopramide) or delay (morphine) gastric emptying influence the absorption of paracetamol. The aim of this study was to develop and standardize a methodology to investigate the effect of gastric emptying on the kinetics of drugs administered in small rodents. The methodology used in the analysis of plasma concentrations of paracetamol was High Performance Liquid Chromatography coupled to diode-array detector and visualization on ultraviolet range (HPLC-DAD-UV), using a Shimadzu Class-VP equipment...