Effect of process variables on particle size and viability of Bifidobacterium lactis Bb-12 in genipin-gelatin microspheres

Gelatin microspheres cross-linked with genipin were developed to encapsulate the probiotic Bifidobacterium lactis Bb-12 The effects of different gelatin concentrations (10-19% w/v), bloom strengths (175 and 300), surfactants, stirring rates during emulsion formation and genipin concentrations (0-10 mM) on the microsphere sizes and viability of bacterial cells were investigated. Principal Component Analysis revealed microsphere size distribution differed depending on the presence or absence of surfactants as well as a trend of increasing micropshere size with increasing gelatin concentration and bloom strength. Lower stirring rates resulted in larger microspheres with higher encapsulation yields of bifidobacteria Microsphere size and cell viability were not significantly (p < 0.05) influenced by increasing genipin concentrations up to 10 mM whereas microsphere stability in simulated gastric juice increased with increasing genipin concentration. The encapsulation yields were higher in 175 bloom strength gelatin microspheres than in 300. Cold-stage scanning electron microscopy showed encapsulated bacteria distributed throughout the genipin cross-linked gelatin matrix.     

Preclinical characterization of WAY-211612: a dual 5-HT uptake inhibitor and 5-HT1A receptor antagonist and potential novel antidepressant

Background and purpose

As a combination of 5-HT selective reuptake inhibitor (SSRI) with 5-HT_1A receptor antagonism may yield a rapidly acting antidepressant, WAY-211612, a compound with both SSRI and 5-HT_1A receptor antagonist activities, was evaluated in preclinical models.

Experimental approach

Occupancy studies confirmed the mechanism of action of WAY-211612, while its in vivo profile was characterized in microdialysis and behavioural models.

Key results

WAY-211612 inhibited 5-HT reuptake (K_i = 1.5 nmol·L⁻¹; K_B = 17.7 nmol·L⁻¹) and exhibited full 5-HT_1A receptor antagonist activity (K_i = 1.2 nmol·L⁻¹; K_B = 6.3 nmol·L⁻¹; I_max 100% in adenyl cyclase assays; K_B = 19.8 nmol·L⁻¹; I_max 100% in GTPγS). WAY-211612 (3 and 30 mg·kg⁻¹, po) occupied 5-HT reuptake sites in rat prefrontal cortex (56.6% and 73.6% respectively) and hippocampus (52.2% and 78.5%), and 5-HT_1A receptors in the prefrontal cortex (6.7% and 44.7%), hippocampus (8.3% and 48.6%) and dorsal raphe (15% and 83%). Acute or chronic treatment with WAY-211612 (3–30 mg·kg⁻¹, po) raised levels of cortical 5-HT approximately twofold, as also observed with a combination of an SSRI (fluoxetine; 30 mg·kg⁻¹, s.c.) and a 5-HT_1A antagonist (WAY-100635; 0.3 mg·kg⁻¹, s.c). WAY-211612 (3.3–30 mg·kg⁻¹, s.c.) decreased aggressive behaviour in the resident-intruder model, while increasing the number of punished crossings (3–30 mg·kg⁻¹, i.p. and 10–56 mg·kg⁻¹, po) in the mouse four-plate model and decreased adjunctive drinking behaviour (56 mg·kg⁻¹, i.p.) in the rat scheduled-induced polydipsia model.

Conclusions and implications

These findings suggest that WAY-211612 may represent a novel antidepressant.     

A cross-sectional study of latent tuberculosis infection,insurance coverage,and usual sources of health care among non-US-born persons in the United States

More than 70% of tuberculosis (TB) cases diagnosed in the United States (US) occur in non-US-born persons, and this population has experienced less than half the recent incidence rate declines of US-born persons (1.5% vs 4.2%, respectively). The great majority of TB cases in non-US-born persons are attributable to reactivation of latent tuberculosis infection (LTBI). Strategies to expand LTBI-focused TB prevention may depend on LTBI positive non-US-born persons’ access to, and ability to pay for, health care.To examine patterns of health insurance coverage and usual sources of health care among non-US-born persons with LTBI, and to estimate LTBI prevalence by insurance status and usual sources of health care.Self-reported health insurance and usual sources of care for non-US-born persons were analyzed in combination with markers for LTBI using 2011–2012 National Health and Nutrition Examination Survey (NHANES) data for 1793 sampled persons. A positive result on an interferon gamma release assay (IGRA), a blood test which measures immunological reactivity to Mycobacterium tuberculosis infection, was used as a proxy for LTBI. We calculated demographic category percentages by IGRA status, IGRA percentages by demographic category, and 95% confidence intervals for each percentage.Overall, 15.9% [95% confidence interval (CI) = 13.5, 18.7] of non-US-born persons were IGRA-positive. Of IGRA-positive non-US-born persons, 63.0% (95% CI = 55.4, 69.9) had insurance and 74.1% (95% CI = 69.2, 78.5) had a usual source of care. IGRA positivity was highest in persons with Medicare (29.1%; 95% CI: 20.9, 38.9).Our results suggest that targeted LTBI testing and treatment within the US private healthcare sector could reach a large majority of non-US-born individuals with LTBI. With non-US-born Medicare beneficiaries’ high prevalence of LTBI and the high proportion of LTBI-positive non-US-born persons with private insurance, future TB prevention initiatives focused on these payer types are warranted.     

Effect of SARS-CoV-2 infection on the liver

There have been numerous concerns about the disease and how it affects the human body since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic began in December 2019. The impact of SARS-CoV-2 on the liver is being carefully investigated due to an increase in individuals with hepatitis and other liver illnesses, such as alcoholic liver disease. Additionally, the liver is involved in the metabolism of numerous drugs used to treat comorbidities and coronavirus disease 2019 (COVID-19). Determining how SARS-CoV-2 affects the liver and what factors place individuals with COVID-19 at a higher risk of developing liver problems are the two main objectives of this study. This evaluation of the literature included research from three major scientific databases. To provide an update on the current impact of COVID-19 on the liver, data was collected and relevant information was incorporated into the review. With more knowledge about the effect of the disease on the liver, better management and therapeutics can be developed, and education can ultimately save lives and reduce the long-term impact of the pandemic on our population.     

髓核摘除Dynesys动态内固定系统固定治疗青壮年单节段腰椎间盘突出症的中长期疗效分析

【摘要】 目的：观察髓核摘除Dynesys动态内固定系统固定治疗青壮年单节段腰椎间盘突出症（lumbar disc heniation，LDH）的中长期疗效。方法：回顾性分析2010年12月～2014年8月于我院骨科手术治疗且资料完整的62例青壮年单节段LDH病患者的临床资料，其中31例采用髓核摘除Dynesys动态内固定系统固定术治疗（Dynesys组），31例采用单纯髓核摘除术治疗（对照组），两组患者的年龄、性别比、体重指数、病程、合并基础病、吸烟史、手术节段等基线数据无显著性差异。收集两组患者手术相关资料及并发症，比较两组术前及末次随访时的疼痛视觉模拟评分（visual analogue scale，VAS）、Oswestry功能障碍指数（Oswestry disability index，ODI）、手术节段和近端邻近节段的椎间盘高度（disc height，DH）、椎间活动度（range of motion，ROM）和椎间盘改良Pfirrmann分级。结果：对照组手术时间和术后住院时间更短、术中出血更少（P<0.05）。Dynesys组3例、对照组1例术中发现硬膜撕裂，予以仔细缝合修补，术后均未发生脑脊液漏；Dynesys组和对照组各有1例患者住院期间因发热使用抗生素治疗，均排除手术部位感染。对照组1例患者术后1个月因切口渗液、愈合不良再入院行清创术。Dynesys组随访72～109个月（91.8±11.1个月）；对照组随访72～116个月（93.7±12.7个月）。末次随访时两组患者腰痛和腿痛VAS评分、ODI均较术前显著性改善（P<0.05），两组同时间点比较无显著性差异（P>0.05）；两组手术节段DH均较术前显著性下降（P<0.05），对照组下降比Dynesys组更显著（P<0.05）；两组近端邻近节段DH较术前均无显著性变化。Dynesys组手术节段ROM在末次随访时得到部分保留（2.7°±2.1°），但较术前显著性降低（P<0.05）；近端邻近节段ROM均较术前显著性增加（P<0.05），但与对照组比较无显著性差异。末次随访时两组手术节段和近端邻近节段的椎间盘改良Pfirrmann分级均较术前进展（P<0.05），对照组手术节段退变进展较Dynesys组更明显（P<0.05）。随访期间Dynesys组所有患者手术节段椎间盘突出均无复发，均未发现内固定断裂及松动并发症，无再手术病例，5例手术节段术前合并不稳患者均采用Dynesys动态固定系统固定，术后未再发节段不稳定；对照组3例患者因椎间盘突出复发且保守治疗无效行椎间融合术，1例患者因术后再发腰痛伴手术节段不稳，行椎间融合术。两组患者均未出现症状性邻近节段退变，总体并发症发生率无显著性差异（P>0.05）。结论：髓核摘除Dynesys动态固定系统固定治疗青壮年单节段腰椎间盘突出症安全有效，可减少复发并保留手术节段一定的活动度。