Cellulose acetate phthalate microparticles containing Vibrio cholerae: steps toward an oral cholera vaccine

Abstract

Oral cholera vaccine (OCV) has been recommended in some endemic areas and epidemic situations since 1999. Although safe and effective vaccines are currently on the market, the burden of transport and storage remains an issue. Herein, we report an approach to develop an alternative OCV in the form of a gastro-resistant powder. Heat-killed Vibrio cholerae (VC) was encapsulated with a spray-drying technique at different temperatures. Cellulose acetate phthalate (Aquacoat® CPD) was chosen as the core polymer and the addition of alginate was studied. The microparticles (MPs) produced were characterized by surface morphology, particle size, drug loading, antigenicity and gastro resistance. The MPs obtained were 6?µm in size and had appropriate drug content, ranging from 8.16 to 8.64%. Furthermore, antigenicity was maintained, never dropping below 85%, and enteric properties were achieved for all the formulations. Next, an in vivo study was carried out with Aquacoat® CPD MP prepared at 80?°C with and without alginate. Two different doses were assayed, 30 and 60?mg, and compared to the VC suspension. The evoked immune responses showed that alginate containing MPs, especially at the 30?mg dose, displayed values that were very similar to those of VC. In conclusion, spray-dried alginate VC MPs seem to be a promising step toward a powder-form cholera vaccination.     

Pulmonary hypertension in hemodialysis patients without arteriovenous fistula: the effect of dialyzer composition

Pulmonary hypertension (PHT) increases mortality rate in hemodialysis (HD) patients. Numerous clinical, hemodynamic, and metabolic abnormalities have been suggested to be associated with the development of PHT in HD patients. We aimed to investigate the acute effects of two different dialyzer membranes on pulmonary arterial pressure (PAP) throughout a HD session in maintenance HD patients. Seventy-four HD patients dialyzed through permanent tunneled jugular central venous catheter were enrolled. A first-use cellulose acetate and high-flux polysulfone dialysis membrane were tested using a crossover design. For each membrane, pre- and post-dialysis pulmonary artery pressures were measured echocardiographically. Elevated pulmonary artery pressure was observed in 68.8% of patients (n = 51), whereas mild PHT was observed in 28.3% of patients (n = 21) and moderate PHT in 40.5% (n = 30). Decrease in pulmonary artery pressure following HD procedure performed using high-flux polysulfone membrane was significantly higher than the decrease observed following HD procedure performed using cellulose acetate membrane (p < 0.05). Significant decrease in pulmonary artery pressures was observed only after HD procedures performed using high-flux polysulfone membrane (p < 0.05). Ultrafiltered volume was only significantly correlated with the decrease in pulmonary artery pressure observed after HD procedure performed through high-flux polysulfone membrane (β = 0.411, p < 0.05). PHT seems to be prevalent among HD patients even in the absence of AV fistula and abnormal cardiac functions. Membrane composition seems to be important, which may overwhelm the improving effects of ultrafiltration.     

RP-HPLC鉴别三七粉中的醋酸地塞米松

 目的 检测三七粉中掺入的醋酸地塞米松。方法 采用反相高效液相色谱法,C₁₈柱,流动相为甲醇-水梯度洗脱或乙腈-四氢呋喃-水(25:18:57)等度洗脱，检测波长240 nm。结果 在两种液相条件下，供试品溶液中均检出醋酸地塞米松，且样品中的醋酸地塞米松与其他杂质峰能有效分离，通过比较供试品和对照品色谱保留时间和其紫外光谱信息，以及样品中峰纯度检查，供试品中含有醋酸地塞米松。结论 本测定方法简便、灵敏、专属性强。     

Factors Affecting the Clinical Course of Follicular Lymphoma: A Multistate Survival Analysis Using Individual Patient Data from Eight Multicenter Randomized Clinical Trials

Introduction/BackgroundLeveraging the Follicular Lymphoma Analysis of Surrogacy Hypothesis database of individual patient data from first-line clinical trials, we studied the clinical course of follicular lymphoma (FL) and investigated clinical factors associated with FL outcomes.Patients and MethodsWe examined 2428 patients from 8 randomized trials using multistate survival models with 4 states: induction treatment, progression, death from FL, and death from other causes. We utilized Aalen-Johansen estimator and Cox models to assess the likelihood of FL outcomes and quantify predictors’ effects.ResultsTwo-year progression, FL-related death, and death from other causes estimates were 26.5%, 3.4% and 1.4%, respectively. FL-associated deaths were the primary cause of mortality within 10 years of follow-up. Male sex (hazard ratio: 1.25; 95% confidence interval: 1.05-1.47), > 4 involved nodal areas (1.51; 1.23-1.86), elevated LDH (1.20; 1.01-1.43), low hemoglobin (1.44; 1.15-1.81), and elevated β-2 levels (1.23; 1.02-1.47) increased risk of progression. CD20-targeting agents reduced risks for progression (0.29; 0.22-0.39), death from FL (0.05; 0.01-0.20), and death from other causes without progression (0.13; 0.05-0.33) and following progression (0.52; 0.30-0.92). Estimated 2-year progression rates were 22.3% and 43.5% with or without CD20-targeting agents, respectively. Two-year FL-associated mortality rate was 8.3% among patients without CD20-targeting agents, 5.4% with B-symptoms, 4.9% with elevated LDH, and 9.1% with low hemoglobin.ConclusionThis study identified independent contributions of baseline clinical factors to distinct outcomes for patients with FL following first-line therapy on a clinical trial. Similar analytical approaches are needed to increase understanding of factors that influence FL outcomes in other settings.     

醋酸曲普瑞林注射液联合炔雌醇环丙孕酮片治疗PCOS不孕症的效果及对相关激素水平的影响

目的探讨醋酸曲普瑞林注射液联合炔雌醇环丙孕酮片治疗多囊卵巢综合征(PCOS)不孕症的效果及对血清睾酮、促甲状腺素水平的影响。方法选取2015年3月至2017年3月湖北省武汉市中西医结合医院诊治的多囊卵巢综合征不孕症患者110例作为研究对象。按随机数字表法分为观察组和对照组,各55例。对照组予醋酸曲普瑞林注射液治疗,观察组予炔雌醇环丙孕酮片与醋酸曲普瑞林联合治疗,比较两组患者的治疗效果及雌激素、睾酮、促甲状腺激素等的水平及超氧化物歧化酶活性。结果观察组的总有效率为96.4%,对照组为80.0%,观察组高于对照组,差异具有统计学意义(P<0.05);在本研究中治疗前两组患者的睾酮、促卵泡激素、黄体生成素、超氧化物歧化酶、促甲状腺素的水平差异无统计学意义(P>0.05),治疗后促卵泡激素水平、超氧化物歧化酶活性均升高,且观察组升高较对照组更多,睾酮、黄体生成素、促甲状腺素水平均下降,且观察组下降更多,差异均具有统计学意义(P<0.05);观察组的累积排卵率为87.27%,累积妊娠率为72.73%,对照组分别为76.27%、45.45%,观察组高于对照组,差异具有统计学意义(P<0.05);观察组的痤疮、月经稀发、多毛症状少于对照组,差异具有统计学意义(P<0.05),两组患者在治疗过程中均未发生不良反应。结论醋酸曲普瑞林注射液联合炔雌醇环丙孕酮片治疗多囊卵巢综合征不孕症的效果较好,可有效提高排卵率、妊娠率,有效调节血性激素、促甲状腺素等激素的水平,增加超氧化物歧化酶活性,在临床上可广泛使用。     

Steroid-resistant nephrotic syndrome: pharmacogenetics and epigenetic points and views

ABSTRACT

Introduction: Glucocorticoids (GCs) are the first-line therapy for patients with nephrotic syndrome (NS), a common glomerular disease, that cause complete remission in most of the cases. In response to the treatment, NS patients are divided into glucocorticoid-sensitive and -resistant. This variation is due to the differences in pharmacokinetics and pharmacodynamics of GCs in each patient that affect the response to the treatment modality. Since the genetic variations in drug-metabolizing enzymes and transporter proteins significantly impact the pharmacokinetics, efficacy and safety of the applied medications, this review highlights the basic mechanisms of genetic variations involved in GCs metabolism in drug-resistant NS patients.

Areas covered: This review explains the pharmacogenetic variations that influence the profile of GCs responses and their pharmacokinetics in NS patients. Moreover, the epigenetic variations including histone modifications and miRNA gene regulation that have an influence on GCs responses will review. A comprehensive literature search was performed using different keywords to the reviewed topics.

Expert opinion: The accumulative data suggest the importance of pharmacogenetic studies to develop personalized therapies and increase the GCs responsiveness in these patients. It is imperative to know that genetic testing does not give absolute answers to all existing questions in steroid resistance.     

Effects of 1.2 μM lead in the laboratory mouse: Developmental and behavioural consequences of chronic treatment

Lead acetate, as a 0.025% (1.2 μM) solution in the drinking fluid, did not adversely affect the reproductive success in breeding mice, weights of pups at birth or cause delays in development. At 21 days, the treated offspring showed reduced weights but these returned to normal values in adulthood. Offspring of treated mice were given 1.2 μM lead acetate as drinking fluid after weaning. The mean daily intake of lead amounted to 2.4 and 2.6 mg/100 g body wt in females and males respectively and caused significant increases in the concentrations of lead in bone and brain. Sequestration of bone was greater in females than males.

The behaviour of the offspring was examined by ethological analysis of social encounters between pairs of unfamiliar mice of similar treatment groups in a neutral cage. Evidence of enhanced reactivity to the test situation was seen in treated males at age 3–4 weeks by increased social investigation during the first 3 min of the 20 min encounter, at 7–8 weeks by decreased immobility in the final 5 min of the test and at 18–19 weeks by an increased duration of exploratory behaviour. However, when encountering females at 30–31 weeks, the treated males showed more immobility than did the controls. Treated females at 3–4 weeks, in the first 3 min of the test, showed a decreased frequency of exploratory behaviour and increased immobility, but at 7–8 and 18–19 weeks they showed enhancement of social and sexual investigation. Behaviour was unaltered at 30–31 weeks in encounters with unfamiliar males. The major effect of lead at this small concentration appeared as changed reactivity to the test environment. Behavioural effects were sex-dependent and altered with increase in age.     

Premature decline in morris water maze performance of aging micrencephalic rats

The rat with methylazoxymethanol-induced micrencephaly is a useful animal model of congenital brain defects and associated cognitive impairment. Born with profound morphological and neurochemical alterations in the forebrain, it shows impaired ability to learn mazes. In order to determine how an animal with such a developmentally damaged brain would function in old age, Long-Evans rats 6, 15, and 24 months of age were tested for their ability to learn to locate a hidden platform in the Morris water maze. The performance of micrencephalic rats of all ages was impaired on acquisition, retention, and transfer trials. Moreover, the magnitude of their acquisition deficit increased with age. It remains to be determined whether the premature decline of the micrencephalic rat in learning the task simply reflects a greater impact on an already compromised brain by neuron loss characteristic of aging brains or whether the prenatal insult alters some basic processes resulting in premature aging.     

{beta}2-Microglobulin Kinetics During Haemofiltration

To study the kinetics of ß₂-microglobulin during haemofiltration,seven patients with end-stage renal failure were treated withthe AN 69 (acrylonitrile), Duo-Flux (cellulose acetate) andF 60 (polysulphone) haemofilter. Low ß₂-microglobulinsieving coefficients and a highly negative filter mass balanceerror were observed during the initial phase of treatment withAN 69 but not with Duo-Flux or F 60, indicating a high degreeof ß₂-microglobulin adsorption by AN 69. Total removalof ß₂-microglobulin was calculated by addition ofthe total amount adsorbed by the membrane and the total amountrecovered in the collected ultrafiltrate. With AN 69 and F 60,total removal of ß₂-microglobulin amounted to 393±135(SD) and 316±35mg per treatment, while total removalwith Duo-Flux was 242±79 mg per treatment. Thus, highlypermeable membranes such as AN 69 or F 60 used in a haemofiltrationmode may nearly balance the presumed generation of ß₂-microglobulinin uraemic patients. During treatment, an increase of the calculatedß₂-microglobulin distribution volume occurred withall three membranes, probably representing extra-to-intracellularwater shifts. The water shifts occurring during haemofiltrationreduce the value of precision of ß₂-microglobulinkinetics and limit the value of the plasma level decrease asan index of ß₂-microglobulin removal.