Molecular docking and cytotoxicity interactions of naringenin and its nano-structured lipid carriers in ER? positive breast cancer

Phytoestrogens are known to have beneficial properties in various carcinomas. They exhibit its efficacy at cellular levels. Naringenin a flavonoidal phytoestrogen is been explored for its antioxidant, cardio protective and cytotoxic function. The low absorbtion and poor bioavailability of naringenin makes it less efficient in targeting tumours at cellular levels. Due to the structural similarity of naringenin with estradiol and considering the affinity of naringenin with estrogen receptor, this study explores the interactions of naringenin on important signaling proteins involved in ER positive breast cancer through molecular docking studies and the prepared naringenin solid lipid nano particles were characterized and studied for its preventive potential against breast cancer cell lines. The lipidoid form of phytoestrogen shows promising cytotoxic potential compared with naringenin.

Glycyrrhizin and Mannitol Nasal Therapy: Cytological and Clinical Outcomes in Chronic Rhinitis

Abstract Introduction Chronic rhinitis (CR) represents a widespread inflammation with a high incidence in the general population. Although it is generally considered a benign condition, CR has a relevant impact on quality of life and requires a specific treatment approach. Objective The aim of the present study was to investigate the efficacy of glycyrrhizin and mannitol intranasal treatment on chronic rhinitis using cytological analysis and subjective evaluation of symptoms. Methods A total of 55 patients suffering from chronic rhinitis were enrolled in the present study, 34 with allergic rhinitis (AR) and 21 with nonallergic rhinitis (NAR). The severity of four different nasal symptoms was determined by using a visual analogue scale (VAS). Specimens obtained by nasal scraping were collected for cytological analysis. Data were acquired before and after a 30-day treatment with glycyrrhizin and mannitol nasal spray. Statistical analyses were performed. Results The VAS scores for all four nasal symptoms considered in the present study, as well as for neutrophil cells, reduced significantly after therapy in both allergic and nonallergic patients. The number of eosinophils was not significantly lower in nonallergic patients. Conclusion A 30-day topical treatment with glycyrrhizin and mannitol may improve nasal symptoms and reduce inflammatory cells in the nasal mucosa in patients with chronic rhinitis without significant contraindications. Further studies could support our results and would better clarify all the aspects of this treatment.

Infrared spectral band screening based on partial least squares is used for the quantitative analysis of mannitol-calcium chloride cocrystal / 药学学报

Mannitol-calcium chloride metal organic framework (MOF) cocrystal significantly improved the tabletability of β-mannitol and could be developed as a new tablet filler. However, mannitol monomer was found in the product during the scale-up production of the excipient, which significantly affected the functional properties of the excipient. In this study, we intend to quantify the multi-component eutectic system of mannitol-calcium chloride. In this experiment, the MOF cocrystal excipient mannitol-calcium chloride cocrystal was used as the model compound, and infrared spectrum was collected. Based on partial least squares regression (PLSR) method, the abnormal bands were removed and the spectrum was preprocessed by normalization. The quantitative correction model of mannitol-calcium chloride MOF cocrystal content in cocrystal excipients was established and compared by two different variable screening methods, genetic algorithm (GA) and competitive adaptive reweighting algorithm (CARS). Two different variable screening methods, GA method and CARS method, were used to screen out 160 and 14 variables, respectively. The mannitol-calcium chloride cocrystal model established by CARS-PLSR method had the best performance, and the average relative error (MRE) and corrected root mean square error (RMSEC) of the model were 0.008 8 and 0.892 5, respectively, the determination coefficient (R2) of the model was increased from 0.978 3 to 0.994 4. The quantitative method of eutectic system established in this study has high prediction accuracy, fast detection speed and good stability, which is of great significance for optimizing the preparation process conditions and quality control methods of such eutectic excipients.

Actualización en el tratamiento del síndrome de hipertensión intracraneana / Update on the management of intracranial hypertension syndrome

Elevated intracranial pressure (ICP) is a devastating complication, with great impact on neurological status and high morbidity and mortality. Intracranial hypertension (ICH) has multiple etiologies. The natural history of this condition can lead to brain death. The successful management of patients with elevated ICP (> 20-25 mmHg) requires fast and timely recognition, judicious use of invasive monitoring and therapies aimed to reversing its underlying cause. Therefore, it must be managed as a neurological emergency. The objective of this review is to present in a friendly way the diagnostic approach and the management of ICH, focused on general practitioners.

Effects of polyol excipient stability during storage and use on the quality of biopharmaceutical formulations / 药物分析学报

Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability.However,some excipients are prone to degradation during repeated use and/or improper storage,and the impurities generated by their degradation are easily overlooked by end users and are usually not strictly monitored,affecting the stability of biopharmaceuticals.In this study,we evaluated the degra-dation profile of polyol excipient glycerol during repeated use and improper storage and identified an unprecedented cyclic ketal impurity using gas chromatography with mass spectrometry(GC-MS).The other polyol excipient,mannitol,was much more stable than glycerol.The effects of degraded glycerol and mannitol on the stability of the model biopharmaceutical pentapeptide,thymopentin,were also evaluated.The thymopentin content was only 66.4％in the thymopentin formulations with degraded glycerol,compared to 95.8％in other formulations after the stress test.Most glycerol impurities(i.e.,aldehydes and ketones)reacted with thymopentin,affecting the stability of thymopentin formulations.In conclusion,this work suggests that more attention should be paid to the quality changes of excipients during repeated use and storage.Additional testing of excipient stability under real or accelerated conditions by manufacturers would help avoid unexpected and painful results.

Comparative study between manitol and sodium picosulfate with magnesium oxide solutions in the preparation for colonoscopy / Estudo comparativo entre as soluções de manitol e picossulfato de sódio com óxido de magnésio no preparo de cólon para colonoscopia

ABSTRACT This prospective, randomized and double-blind study aims to compare two different protocols used for bowel preparation in patients scheduled for colonoscopy. The protocols were composed by solutions of Mannitol or sodium picosulfate combined with magnesium oxide. Patients from the proctology outpatient clinic of the General Surgery Unit of the Regional Hospital of Asa Norte (HRAN) comprised the sample of this study. Both the patients and the colonoscopist had no prior knowledge of the substance used to prepare bowel, which was randomly distributed among the participants. Both protocols demonstrated good and similar results regarding the efficiency of colon preparation, although the review of literature shows a difference in favor of preparation made with Mannitol solution regarding the colon neatness during the exam. In line with the literature, patients who used Mannitol solution had more side effects, highlighting the significant difference found for vomiting and sleep impairment. The preparation with Sodium Picosulfate with Magnesium Oxide was significantly superior in relation to the ease of ingestion perceived by the patients.

RESUMO Estudo prospectivo, randomizado e duplo-cego com o objetivo de comparar dois protocolos diferentes utilizados para o preparo de cólon em pacientes que realizaram colonoscopia: solução de Manitol; e solução de Picossulfato de Sódio combinado com Óxido de Magnésio. Para avaliar qual protocolo proporciona melhores resultados, 90 pacientes do ambulatório de proctologia da Unidade de Cirurgia Geral do Hospital Regional da Asa Norte (HRAN) compuseram a amostra deste estudo. Tanto os pacientes quanto o colonoscopista não tiveram prévio conhecimento da substância utilizada para o preparo do cólon, a qual foi distribuída randomicamente entre os participantes. Os dois protocolos demonstraram bons e semelhantes resultados acerca da eficiência do preparo do cólon, embora a literatura estudada tenha demonstrado diferença significativa em favor do preparo feito com solução de Manitol em relação a limpeza do cólon durante o exame. Em consonância com a literatura, os pacientes que utilizaram solução de Manitol apresentaram mais efeitos colaterais, destacando-se a diferença significativa encontrada para vômito e distúrbios do sono. O preparo com Picossulfato de Sódio com Óxido de Magnésio foi relevantemente superior em relação à facilidade de ingestão percebida pelos pacientes.

Effects of slow intravenous infusion of low-dose mannitol on hemodynamics in patients after cardiac surgery under cardiopulmonary bypass / 中华胸心血管外科杂志

Objective:To investigate the effect of slow intravenous infusion of low-dose mannitol on the hemodynamics of patients after cardiopulmonary bypass.Methods:Prospective, continuous inclusion of 62 patients after cardiac surgery under cardiopulmonary bypass. By random number method, they were divided into normal treatment group(group C) with 29 cases and mannitol treatment group(group M) with 33 cases. Group C was treated according to the postoperative routine treatment measures. On the basis of conventional treatment, group M received intravenous infusion of 20% mannitol injection 0.25 g/kg at 1、8、24 hours after operation, and the intravenous infusion time was 60 minutes each time. According to the hemodynamic changes during the two groups of treatment, the effect of slow intravenous infusion of low-dose mannitol on patients after cardiopulmonary bypass under cardiopulmonary bypass was analyzed.Results:In group M, CI and SVI were significantly increased after use of mannitol than before, with statistical significance( P<0.01). SVRI showed a downward trend, and the changes were statistically significant after use of mannitol( P<0.01). PAWP increased first and then decreased after operation, and the changes were statistically significant after mannitol use than before( P<0.05). RAP and MPAP had no significant changes after the first use of mannitol, but the changes after the latter two use mannitol were statistically significant than before( P<0.05). Repeated-measurement data analysis of variance was performed on the hemodynamic parameters of each group, and the results were all P<0.01. Conclusion:Postoperative slow intravenous infusion of low-dose mannitol optimizes hemodynamic status, increases stroke volume, reduces cardiac preload, improves systemic and pulmonary circulation resistance, and promotes recovery of postoperative cardiopulmonary function.

Fatores predisponentes do volume residual gástrico após preparo expresso com manitol / Gastric residual volume factors after bowel preparation with mannitol express

ABSTRACT BACKGROUND: Bowel preparation with mannitol is a well-established method in Brazil. However, factors that interfere with the gastric emptying time period are yet to be known. Knowing these factors may favor the examination scheduling logistics and the individualized orientation for each patient. OBJECTIVE: Know the factors that can contribute to the gastric emptying time after intestinal preparation with express mannitol. METHODS: This is a prospective observational study to know factors that may contribute on the gastric emptying timing: predominant type of diet, comorbidities, medication usage, previous surgeries, number of evacuation per week, bearer of bowel obstipation, fecal type, diet type, number of evacuations after the home usage of bisacodyl before the ingestion of mannitol and number of evacuations after the ingestion of mannitol until reaching a proper bowel preparation. Before starting the colonoscopy exam, an upper digestive endoscopy exam was made to aspirate the gastric content. RESULTS: Sample was composed of 103 patients, 55 (53.4%) women, medium age 61 (±12.1) years, medium weight 75.3 (±14.1) kg, medium height 1.7 (±10) m and medium BMI of 26.6 (±3.9) kg/m2. Average gastric residual volume was 120.9 (0-900) mL. Gastric residual volume (GRV) below 100 mL (GRV ≤100 mL) occurred in 45 (43.6%) patients, 24 (53.3%) women, medium age of 61.0 years and medium BMI of 26.7 kg/m2. Gastric residual volume above 100 mL (GRV >100 mL) occurred on 58 (56.3%) patients, 29 (50%) women, medium age of 61.0 years and medium BMI of 26.2 kg/m2. Comparing both groups, average fasting time period after the ingestion of mannitol was significantly higher on the group with GRV ≤100 mL than group with GRV >100 mL, 123.1 (60-246) vs 95.3 (55-195) minutes, respectively. There was also statistical significance concerning the usage of ezetimibe 6 (13.7%) in the group with GRV ≤100 mL and statistical significance in the group with GRV >100 mL concerning the usage of paroxetine 3 (6.7%) and tadalafil 3 (6.7%) and surgical history of prostatectomy 3 (6.7%) and bridle withdrawal 3 (6.7%). CONCLUSION: We may conclude in this study that the usage of ezetimibe and fasting above 2 hours after the ingestion of mannitol decrease significantly the incidence of a GRV >100 mL. The usage of paroxetine, tadalafil and surgical history of prostatectomy or bridle withdrawal may contribute to increase de incidence of a GRV >100 mL.

RESUMO CONTEXTO: O preparo intestinal com manitol é um método bem estabelecido no Brasil. No entanto, os fatores que interferem no tempo de esvaziamento gástrico ainda não são conhecidos. O conhecimento desses fatores pode favorecer a logística de agendamento do exame e a orientação individualizada para cada paciente. OBJETIVO: Estudar os fatores que podem contribuir para o tempo de esvaziamento gástrico após o preparo intestinal com manitol expresso. MÉTODOS: Trata-se de um estudo observacional prospectivo com o objetivo de conhecer os seguintes fatores que podem contribuir no tempo de esvaziamento gástrico: tipo de dieta predominante, comorbidades, uso de medicamentos, cirurgias anteriores, número de evacuações por semana, portador de obstipação intestinal, tipo fecal, tipo de dieta, número de evacuações após o uso domiciliar de bisacodil antes da ingestão de manitol e número de evacuações após a ingestão de manitol até atingir o preparo intestinal adequado. Antes de iniciar o preparo intestinal, os pacientes responderam a um questionário clínico. O endoscópio foi introduzido para aspirar o conteúdo gástrico, antes de iniciar a colonoscopia. RESULTADOS: A amostra foi composta por 103 pacientes, sendo 55 mulheres, com média de idade de 61 anos, peso médio de 75,3 kg, altura média de 1,7 m e IMC médio de 26,6 kg/m2. O volume residual gástrico médio medido foi 120,9 (0-900) mL. Volume residual gástrico inferior a 100 mL (VRG ≤100 mL) foi encontrado em 45 (43,6%) pacientes, sendo 24 (53,3%) mulheres, com média de idade de 61,0 anos e IMC médio de 26,7 kg/m2. Volume residual gástrico acima de 100 mL (VRG >100 mL) ocorreu em 58 (56,3%) pacientes, sendo 29 (50%) mulheres, com idade média de 61,0 anos e IMC médio de 26,2 kg/m2. Comparando os dois grupos, notou-se que o tempo médio de jejum após a ingestão de manitol foi significativamente maior no grupo com VRG ≤100 mL do que no grupo com VRG> 100 mL, 123,1 (60-246) vs 95,3 (55-195) minutos, respectivamente. Também houve significância estatística em relação ao uso de ezetimiba 6 (13,7%), sendo maior no grupo com VRG ≤100 mL. Além disso, houve significância estatística no grupo com VRG >100 mL quanto ao uso de paroxetina 3 (6,7%) e tadalafil 3 (6,7%) e história cirúrgica de prostatectomia 3 (6,7%) e retirada de bridas 3 (6,7%). CONCLUSÃO: Podemos concluir neste estudo que o uso de ezetimiba e o jejum acima de 2 horas após a ingestão de manitol diminuem significativamente a incidência de um VRG> 100 mL. O uso de paroxetina, tadalafil e história cirúrgica de prostatectomia ou retirada de bridas podem contribuir para o aumento da incidência de um VRG >100 mL.

Comparison of half-molar sodium lactate and mannitol to treat brain edema in severe traumatic brain injury: A systematic review / 中华创伤杂志(英文版)

PURPOSE@#Hypertonic fluids such as mannitol and half-molar sodium lactate are given to treat intracranial hypertension in patients with severe traumatic brain injury (TBI). In this study, sodium lactate was compared to mannitol in patients with TBI to investigate the efficacy in reducing intracranial pressure (ICP).@*METHODS@#This study was a systematic review with literature research on articles published in any year in the databases of PubMed, ScienceDirect, Asian Journal of Neurosurgery, and Cochrane Central Register of Controlled Trials. The keywords were "half-molar sodium lactate", "mannitol", "cerebral edema or brain swelling", and "severe traumatic brain injury". The inclusion criteria were (1) studies published in English, (2) randomized control trials or retrospective/prospective studies on TBI patients, and (3) therapies including half-molar sodium lactate and mannitol and (4) sufficient data such as mean difference (MD) and risk ratio (RR). Data analysis was conducted using Review Manager 5.3.@*RESULTS@#From 1499 studies, a total of 8 studies were eligible. Mannitol group reduced ICP of 0.65 times (MD 0.65; p = 0.64) and improved cerebral perfusion pressure of 0.61 times (MD 0.61; p = 0.88), better than the half-molar group of sodium lactate. But the half-molar group of sodium lactate maintained the mean arterial pressure level of 0.86 times, better than the mannitol group (MD 0.86; p = 0.09).@*CONCLUSION@#Half-molar sodium lactate is as effective as mannitol in reducing ICP in the early phase of brain injury, superior over mannitol in an extended period. It is able to prevent intracranial hypertension and give better brain tissue perfusion as well as more stable hemodynamics. Blood osmolarity is a concern as it increases serum sodium.

Intravenous Mannitol reduces intracompartmental pressure following tibia fractures: A randomized controlled trial / 中华创伤杂志(英文版)

PURPOSE@#Impending compartment syndrome is a common event following closed tibia fractures, which can progress to sinister compartment syndrome. Fasciotomy is the only definitive treatment available, though it has its own drawbacks and complications. Medical management at present consists of limb elevation and adequate hydration. This study aims at determining whether intravenous administration of Mannitol reduced the intracompartmental pressure in patients with closed tibial fractures.@*METHODS@#This is a double blinded, randomized control trial done in a single tertiary care center in India. Forty-five patients were recruited between February 2012 and October 2012. Forty patients who presented to the emergency department with isolated, closed, high velocity, and proximal 2/3 tibia fractures were included in this study. Patients with contraindication to Mannitol were excluded. They were allocated into 2 groups by the investigator using computer generated randomization. The pressure in the anterior compartment of the leg was measured with a handheld Stryker pressure monitor. Then either 20% Mannitol or 0.9% normal saline as given intravenously in a blinded manner, based on the randomization. The intracompartmental pressure was measured at 0, 1 and 3 h after the infusion. The participant, investigator and statistician were masked to the group assessment.@*RESULTS@#There was no difference in intracompartmental pressures at 1 or 3 h, between the groups. However, in patients with the baseline of compartmental pressures ≥30 mmHg, Mannitol showed a marked reduction in pressure of 8.5 mmHg at 1 h compared to almost no change in pressure in the saline group. There were no adverse events with the use of Mannitol.@*CONCLUSIONS@#This preliminary study appears to show that Mannitol is useful in the management of the increased compartment pressure. The limitations of this study were that it only involved a small group of patients and the baseline pressures in both the groups were not comparable. More studies are required before the use of Mannitol as a standard of care in the management of compartment syndrome can be established.

Genotoxicity assessment of three reference chemicals in rat hepatocytes by alkaline comet assay / 上海预防医学

Objective:To establish a comet test method for detection of genotoxicity of three reference chemicals in rat liver cells. Methods:6-10 week old Sprague Dawley rats were randomly divided into 4 groups， with normal saline （0.9% NaCl solution） as negative control group. Animals in three test groups were treated， respectively， with ethyl methanesulfonate （EMS） 200 mg/kg， N-methyl-N-nitrosourea （MNU） 50 mg/kg， and D-mannitol 2 000 mg/kg. There were 10 animals in each group， 5 males and 5 females. The animals received two times （21 h interval） of test compounds through intragastric administration， and their clinical symptoms and body weight changes were recorded during the experiment. The rats were sacrificed 3 h after the last exposure. The liver was weighed， then used to prepare single-cell suspensions for the alkaline comet test which determines the average tail DNA content percentage （DNA%） of hepatocytes and other comet indicators. Results:（1） D-mannitol， EMS and MNU did not show significant toxicity in the whole animal. （2） The mean values of tail DNA content percentage （DNA%） of rat hepatocytes in EMS ［（60.07±24.69）%］ and MNU ［（41.66±22.35）%］ groups were higher than that in the negative control group ［（2.32±1.39）%］ and the difference was statistically significant （P<0.05）. The difference between D-mannitol group ［（3.06±3.30）%］ and the negative control group was not significant （P>0.05）. Conclusion:This laboratory has established a comet test method using hepatocytes from treated rats. Among three testing chemicals， EMS and MNU have displayed genotoxicity by this assay， but no genotoxicity was observed in D-mannitol treated animals.

Assessment of tolerance and acceptability between mannitol solution and polyethylene glycol as bowel preparation for colonoscopy: a three-center study / Evaluación de tolerancia y aceptabilidad entre la solución de manitol y el polietilenglicol como preparación intestinal para la colonoscopía: un estudio de tres centros

ABSTRACT Introduction: Adequate bowel preparation is one of the most important factors related to the yield of colonoscopy. Low quality bowel preparation has been associated with lower adenoma detection rates and increased healthcare expenses. Bowel preparation is a major impediment to undergo colonoscopy since it is perceived as an unpleasant experience by patients. Objective: This study was aimed to assess tolerance and acceptability of the bowel preparation using either polyethylene glycol (PEG) or mannitol solution. Materials and methods: We enrolled 140 patients with indications of screening for colorectal cancer or with suspected large bowel diseases. They received either mannitol solution or PEG as bowel preparation. Patients were asked to fill a questionnaire about the bowel preparation experience. Results: Patients perceived more burdensome the preparation with PEG than mannitol for the variables nausea overall experience, post-procedure discomfort, disagreeable flavor, volume ingested and cost (p<0.05). A similar tolerance was reported for abdominal pain, bloating and anal irritation (p>0.05). The acceptability was 82.9% and 71.4% in the Mannitol group and in the PEG group, respectively (p=0.10). Conclusion: Acceptance of the bowel preparation between mannitol solution and PEG was comparable. However, mannitol was better tolerated by the patients in regard to most of the evaluated items.

RESUMEN Introducción: La preparación intestinal adecuada es uno de los factores más importantes relacionados con el rendimiento de la colonoscopía. La preparación intestinal de baja calidad se ha asociado con tasas de detección de adenoma más bajas y mayores gastos de atención sanitaria. La preparación intestinal es un impedimento importante para someterse a una colonoscopía, ya que los pacientes la perciben como una experiencia desagradable. Objetivo: Este estudio tuvo como objetivo evaluar la tolerancia y la aceptabilidad de la preparación intestinal utilizando polietilenglicol (PEG) o solución de manitol. Materiales y métodos: Fueron incluidos 140 pacientes con indicación de pesquisa de cáncer colorrectal o con sospecha de enfermedades del intestino grueso. Los pacientes recibieron solución de manitol o PEG como preparación intestinal. Se pidió a los pacientes que completaran un cuestionario sobre la experiencia de preparación intestinal. Resultados: Los pacientes percibieron más agobiante la preparación con PEG que el manitol para las variables náuseas, experiencia general, molestias posteriores al procedimiento, sabor desagradable, volumen ingerido y costo (p<0,05). Se informó una tolerancia similar para el dolor abdominal, distensión abdominal e irritación anal (p>0,05). La aceptabilidad fue de 82,9% y 71,4% en el grupo de manitol y en el grupo de PEG, respectivamente (p=0,10). Conclusión: La aceptación de la preparación intestinal entre la solución de manitol y el PEG fue comparable. Sin embargo, el manitol fue mejor tolerado por los pacientes con respecto a la mayoría de las variables evaluadas.

Evaluation of pH and residual gastric volume after colon preparation with mannitol: prospective randomized study comparing procedure performed after 3 hours versus 6 hours

OBJECTIVES: Our goal was to compare the hydrogen potential (pH) and residual gastric volume (RGV) of patients undergoing colonoscopy after 3 and 6 hours of colon preparation with mannitol. METHODS: We described a prospective randomized trial with a 50:50 allocation rate of two distinct times of colonoscopy after colon preparation with 10% mannitol. We included outpatients aged over 18 years, with no history of gastric surgeries and an American Society of Anesthesiologists (ASA)-rated anesthetic risk below III. Colonoscopy was performed after upper digestive endoscopy at two different times: 3 versus 6-hour after mannitol ingestion. During upper gastrointestinal endoscopy, we measured RGV and evaluated pH with a digital pH meter. Clinical trials.gov: 71123317.9.3001.0065 RESULTS: We randomized a total of 100 participants to the 3 and 6-hour groups, with the patients in the 6-hour group being younger and presenting a higher body mass index (BMI). The intervention did not result in any statistically significant differences between the two groups, neither for the RGV (p=0.98) or the pH (p=0.732). However, the subgroup of patients with diabetes mellitus showed statistically significant higher RGV values in the 3-hour group. CONCLUSION There was no difference between RGV and pH values at 3 versus 6-hour after bowel preparation with mannitol, except for RGV in diabetic patients at 3 hours. As prolonged fasting protocols may result in adverse events such as dehydration and electrolyte imbalance, we can infer that colonic preparation with mannitol in shorter fasting periods, such as 3 hours, can be adopted safely and routinely.

Alanyl-glutamine protects the intestinal barrier function in trained rats against the impact of acute exhaustive exercise

Strenuous exercise triggers deleterious effects on the intestinal epithelium, but their mechanisms are still uncertain. Here, we investigated whether a prolonged training and an additional exhaustive training protocol alter intestinal permeability and the putative effect of alanyl-glutamine (AG) pretreatment in this condition. Rats were allocated into 5 different groups: 1) sedentary; 2 and 3) trained (50 min per day, 5 days per week for 12 weeks) with or without 6 weeks oral (1.5 g/kg) AG supplementation; 4 and 5) trained and subjected to an additional exhaustive test protocol with or without oral AG supplementation. Venous blood samples were collected to determine gasometrical indices at the end of the 12-week protocol or after exhaustive test. Lactate and glucose levels were determined before, during, and after the exhaustive test. Ileum tissue collected after all experimental procedures was used for gene expression analysis of Zonula occludens 1 (ZO-1), occludin, claudin-2, and oligopeptide transporter 1 (PepT-1). Intestinal permeability was assessed by urinary lactulose/mannitol test collected after the 12-week protocol or the exhaustive test. The exhaustive test decreased pH and base excess and increased pCO2. Training sessions delayed exhaustion time and reduced the changes in blood glucose and lactate levels. Trained rats exhibited upregulation of PEPT-1, ZO-1, and occludin mRNA, which were partially protected by AG. Exhaustive exercise induced intestinal paracellular leakage associated with the upregulation of claudin-2, a phenomenon protected by AG treatment. Thus, AG partially prevented intestinal training adaptations but also blocked paracellular leakage during exhaustive exercise involving claudin-2 and occludin gene expression.

Water deficit on germination and vigour in seeds of the Jambu / Déficit hídrico na germinação e vigor de sementes d e jambu

Water availability influences plant metabolism during the various stages of development, especially in the period between germination and seedling emergence. The aim of this study was to evaluate the effect of water deficit during the germination process on seeds of A. oleracea. The experiment was carried out in a completely randomised design, with four replications of 50 seeds. The treatments were arranged in a 5 x 2 factorial scheme, with the first factor consisting of the osmotic potentials (-0.2, -0.4, -0.6, -0.8 and distilled water for the potential 0.0 MPa) and the second factor consisting of two lots of seed. The germination test was carried out on substrates moistened with solutions of mannitol and polyethylene glycol (PEG 6000) at the various potentials, in a Biochemical Oxygen Demand (BOD) germinator at a temperature of 30°C and under constant light. The test was evaluated daily for 14 days, considering the seeds that had a root length equal to or greater than two millimetres as having germinated. The variables under analysis were germination, germination speed index, seedling length and seedling dry weight. The germination process of A. oleracea is compromised at water potentials of -0.2 MPa and -0.4 MPa when submitted to PEG and mannitol respectively. Seeds from Lot 1 were more tolerant to the water deficit than were those from Lot 2.

A disponibilidade de água influencia o metabolismo vegetal nas diversas etapas do desenvolvimento, especialmente no período entre a germinação e a emergência das plântulas. Diante disso, objetivou-se avaliar o efeito do déficit hídrico durante o processo de germinação de sementes de A. oleracea. O experimento foi conduzido em delineamento experimental inteiramente casualizado, com quatro repetições de 50 sementes. Os tratamentos foram arranjados em esquema fatorial 5 x 2, com o primeiro fator constituído pelos potenciais osmóticos (-0,2; -0,4; -0,6; -0,8 e água destilada para o potencial 0,0 MPa) e o segundo dois lotes de sementes. Para isso, o teste de germinação foi realizado em substratos umedecidos com soluções de manitol e polietilenoglicol (PEG 6000) nos diversos potenciais, em germinador do tipo Biochemical Oxigen Demand (B.O.D.) sob a temperatura de 30 °C e luz constante. O teste foi avaliado diariamente durante 14 dias, sendo considerado como germinadas, as sementes que apresentavam extensão radicular igual ou superior a dois milímetros. As variáveis analisadas foram germinação, índice de velocidade de germinação, comprimento de plântulas e massa seca de plântulas. O processo germinativo de sementes de A. oleracea é comprometido a partir de potenciais hídricos de -0,2 MPa e -0,4 MPa, quando submetidas ao PEG e manitol respectivamente. As sementes provenientes do lote 1 mostraram-se mais tolerantes ao déficit hídrico que as do lote 2.

Double blinded randomized clinical trial to assess the effectiveness of several preparations for colonoscopy / Ensaio clínico randomizado duplo cego para avaliar a eficácia de várias preparações para colonoscopia

ABSTRACT Introduction: Colonoscopy is the screening gold standard to investigate several conditions in the colon. The excellence of preparation is a determining factor for a quality colonoscopy. Objective: Compare the quality of colon preparations for colonoscopy with different kinds of laxative medications in a public hospital of Belo Horizonte, Brazil. Method: A prospective double blind randomized clinical trial was conducted from June 2016 to March 2017. A total of 117 Patients were randomised in four groups to receive a type of preparation (Sodium picosulfate, Mannitol, Lactitol, Lactulose). The patients answered a questionnaire and peripheral blood samples were collected before and after the preparation.The quality of the cleansing was accessed according to the Boston Bowel Preparation Scale. Results: 99.1% of patients have taken the recommended dose and 79.5% reported a good tolerability. Endoscopists performed complete colonoscopy in 89.7%, with an polipectomy rate of 47%. The total effectiveness rate of the solutions were 88%. There were no statistically significant differences between groups (p = 0.271). Regarding the laboratory parameters, differences were seen in the pre- and post-test values of sodium, chlorine and creatinine but without exceeding reference values. Conclusion: The four preparations were effective for colon cleansing, with good acceptance, differing only as for costs.

RESUMO Introdução: a colonoscopia é o padrão ouro de triagem para pesquisa de várias doenças colônicas. A excelência de preparação é um fator determinante para uma colonoscopia de qualidade. Objetivo: Comparar a qualidade das preparações do cólon para colonoscopia com diferentes tipos de medicamentos laxantes em um hospital público de Belo Horizonte, Brasil. Método: Foi realizado um ensaio clínico randomizado duplo cego prospectivo de junho de 2016 a março de 2017. Um total de 117 pacientes foi randomizado em quatro grupos para receber um tipo de preparação (picossulfato sódico, manitol, lacticol, lactulose). Os pacientes responderam a um questionário e amostras de sangue periférico foram coletadas antes e depois da preparação. A qualidade da limpeza foi acessada de acordo com a Boston Bowel Preparation Scale. Resultados: 99,1% dos pacientes tomaram a dose recomendada e 79,5% relataram boa tolerabilidade. Os endoscopistas realizaram colonoscopia completa em 89,7%, com taxa de polipectomia de 47%. A taxa de eficácia total das soluções foi de 88%. Não houve diferenças estatisticamente significantes entre os grupos (p = 0,271). Em relação aos parâmetros laboratoriais, foram observadas diferenças nos valores pré e pós-teste de sódio, cloro e creatinina, mas sem exceder os valores de referência. Conclusão: As quatro preparações foram eficazes para limpeza do cólon, com boa aceitação, diferindo apenas quanto aos custos.

Intestinal preparations for colonoscopy. Comparative study: mannitol, picosulphate and macrogol / Preparos intestinais para colonoscopia. Estudo comparativo: manitol, picossulfato e macrogol

ABSTRACT Bowel preparation is mandatory prior to elective colonoscopy and their effectiveness is closely related to the quality of the examination. There are many preparations on the market and there is no consensus on which is best. This study aimed to compare three solutions for colon preparation in patients undergoing colonoscopy. We conducted a prospective study with 61 patients divided randomly into three groups: one that received a standard dose of macrogol, another received a standard dose of 10% mannitol and another received a standard dose of sodium picosulphate. Patients and examining endoscopists responded to questionnaires for compiling data. In the results we noticed that 10% mannitol, despite being less tolerated by the patient when compared to sodium picosulphate, presents better results in colonic cleaning, being therefore superior in this regard. Macrogol was considered as an intermediate in relation to the other two preparations. As for tolerability, preference is given to sodium picosulphate as best tolerated, followed by mannitol and by macrogol, which is poorly tolerated by the patient. We conclude that as the main objective of bowel preparation in colonoscopy is the quality of colonic cleaning, 10% mannitol was superior to the other preparations studied.

RESUMO O preparo intestinal é mandatório antes da realização das colonoscopias eletivas e sua eficácia está intrinsecamente relacionada à qualidade do exame. Existem diversos preparos no mercado e não há consenso sobre qual é melhor. Este estudo teve como objetivo comparar três soluções para preparo de cólon em pacientes submetidos à colonoscopia. Foi realizado um estudo prospectivo com 61 pacientes distribuídos de forma randomizada em três grupos: um recebeu macrogol, outro manitol a 10% e outro picossulfato de sódio em doses padrão. Os pacientes e os endoscopistas examinadores responderam a questionários para compilação de dados. Nos resultados notamos que o manitol a 10%, apesar de ser menos tolerado pelo paciente quando comparado ao picossulfato de sódio, apresenta melhores resultados na limpeza colônica, sendo, portanto, superior neste quesito. O macrogol foi considerado como intermediário em relação aos outros dois preparos. Quanto à tolerabilidade, a preferência recai sobre o picosulfato de sódio como o mais bem tolerado, seguido pelo Manitol; macrogol foi o menos tolerado pelo paciente. Concluímos que, como o principal objetivo do preparo intestinal na colonoscopia é a qualidade da limpeza colônica, o manitol a 10% mostrou-se superior aos demais preparos estudados.

Activators and Inhibitors of α-glucosidase from Penicillium chrysogenum

α-glucosidase (EC: 3.2.1.20) from Penicillium chrysogenum Thom ATCC 10106 was induced by GSH at the lower concentrations. H2O2 was inhibitor at all tested concentrations and the IC50 was 92.2%v/v. AMP, ADP and ATP enhanced the activity revealing that α-glucosidase is endothermic enzyme. The chelating agents are ethylenediaminetetraacetate (EDTA), α-α-dipyridyl and o-phenanthroline inhibited the enzyme. IC50 for these three compounds were 7.1, 10.2 and 10.9 mM, respectively. The highest activity of α-glucosidase was recorded at 150 mM phosphate buffer. Mannitol as polyol protected the enzyme against heat inactivation. The five sugars trehalose, lactose, raffinose, glucose and sucrose protected α-glucosidase against thermo-inactivation at 60ºC. Also, sarcosine as a product of glycine provided α-glucosidase with appreciable thermostability at 60ºC.

The KAAACI Standardization Committee Report on the procedure and application of the bronchial provocation tests

Bronchial provocation tests are of value in the evaluation of airway hyperresponsiveness. Nonspecific bronchial challenge (methacholine, mannitol, exercise, etc.) is used when the symptoms, physical examination, and measurements of pulmonary function are unremarkable in the diagnosis of asthma, when a patient is suspected of having occupational asthma or exercise-induced bronchoconstriction (EIB), and when a screening test for asthma or EIB is required for some occupational groups in whom bronchospasm would pose an unacceptable hazard. Methacholine inhalation challenge is most widely used pharmacologic challenge and highly sensitive. For appropriate interpretation of the results of methacholine provocation, it is important to perform the test with the standardized protocol and to recognize that inhalation methods significantly influence the sensitivity of the procedure. Indirect challenges (e.g., mannitol and exercise) correlate with airway inflammation and are more specific but less sensitive for asthma. Indirect provocation tests are used to confirm asthma, to differentiate asthma from other airway diseases, and to evaluate EIB.

Comparison of different bowel preparation methods for capsule endoscopy / 中国内镜杂志

Objective To explore the optimal bowel preparation for capsule endoscopy (CE). Methods 102 patients were recruited for CE and randomly divided into 3 groups. The group A (n = 40) : patients received polyethylene glycol electrolyte powder (PEG) 137.12 g dissolved in 2 000 ml water at 21:00 one day prior to CE, and taken PEG 68.56 g dissolved in 1 000 ml of water four hours before the procedure. Group B (n = 32): patients received PEG 205.68 g dissolved in 3 000 ml of water four hours prior to CE. Group C (n = 30): patients used a 500 ml 20% mannitol and 2 500 ml water bowel preparation four hours prior to CE. All patients were treated with 120 mg simethicone immediately after swallowing CE. The incidences of adverse events, small-bowel preparation quality and transit time were analyzed. Results The adverse effects rate in each group was similar (15.00%, 15.63% vs 16.67%, P > 0.05). The small-bowel preparation quality was better in both B and C groups than A group (P < 0.05). In the C Group, small-bowel preparation quality was slightly better than the B group, but the difference was not statistically significant (P > 0.05). In comparison with patients in both B and C groups, those in A group had a longer small-bowel transit time (P < 0.05), whereas there was no significant difference between B and C group (P > 0.05). Conclusion Bowel cleansing effect was better in single dose regimen than split dose protocol. The single dose regimen of 500 ml 20% Mannitol for bowel preparation is suitable prior to CE.