Lipid based nanocarriers: a translational perspective

Over the recent couple of decades, pharmaceutical field has embarked most phenomenal noteworthy achievements in the field of medications as well as drug delivery. The rise of Nanotechnology in this field has reformed the existing drug delivery for targeting, diagnostic, remedial applications and patient monitoring. The convincing usage of nanotechnology in the conveyance of medications that prompts an extension of novel lipid-based nanocarriers and non-liposomal systems has been discussed. Present review deals with the late advances and updates in lipidic nanocarriers, their formulation strategies, challenging aspects, stability profile, clinical applications alongside commercially available products and products under clinical trials. This exploration may give a complete idea viewing the lipid based nanocarriers as a promising choice for the formulation of pharmaceutical products, the challenges looked by the translational process of lipid-based nanocarriers and the combating methodologies to guarantee the headway of these nanocarriers from bench to bedside.     

Canagliflozin,a sodium glucose co-transporter 2 inhibitor,reduces post-meal glucose excursion in patients with type 2 diabetes by a non-renal mechanism: results of a randomized trial

Objective

Canagliflozin is a sodium glucose co-transporter 2 inhibitor approved for treating patients with type 2 diabetes. This study evaluated renal and non-renal effects of canagliflozin on postprandial plasma glucose (PG) excursion in patients with type 2 diabetes inadequately controlled with metformin.

Materials/Methods

Patients (N = 37) were randomized to a four-period crossover study with 3-day inpatient stays in each period and 2-week wash-outs between periods. Patients received Treatments (A) placebo/placebo, (B) canagliflozin 300 mg/placebo, (C) canagliflozin 300 mg/canagliflozin 300 mg, or (D) canagliflozin 300 mg/canagliflozin 150 mg on Day 2/Day 3 in one of four treatment sequences (similar urinary glucose excretion [UGE] expected for Treatments B–D). A mixed-meal tolerance test (MMTT) was given 20 minutes post-dose on Day 3 of each period.

Results

A single dose of canagliflozin 300 mg reduced both fasting and postprandial PG compared with placebo, with generally similar effects on fasting PG and UGE observed for Treatments B–D. An additional dose of canagliflozin 300 mg (Treatment C), but not 150 mg (Treatment D), prior to the MMTT on Day 3 provided greater postprandial PG reduction versus placebo (difference in incremental glucose AUC_0–2h, − 7.5% for B vs A; − 18.5% for C vs A; − 12.0% [P = 0.012] for C vs B), leading to modestly greater reductions in total glucose AUC_0–2h with Treatment C versus Treatment B or D. Canagliflozin was generally well tolerated.

Conclusions

These findings suggest that a non-renal mechanism (ie, beyond UGE) contributes to glucose lowering for canagliflozin 300 mg, but not 150 mg.     

血清胃蛋白酶原检测在慢性萎缩性胃炎筛查中的价值

目的探讨血清胃蛋白酶原Ⅰ(PGⅠ)、胃蛋白酶原Ⅰ/胃蛋白酶原Ⅱ(PGⅠ/PGⅡ)比值(PGR)与慢性萎缩性胃炎的关系,确定其在萎缩性胃炎中的变化规律。方法选择在我院消化科行胃镜检查符合入选研究标准的200例患者,根据组织病理学诊断结果分为慢性非萎缩性胃炎组(135例)和慢性萎缩性胃炎组(65例)。采用化学发光方法定量测定空腹血清PGⅠ、PGⅡ,并计算PGⅠ/PGⅡ比值(PGR)。结果慢性萎缩性胃炎组与非萎缩性胃炎组血清PGⅠ分别为(78.55±15.42)μg/L和(130.51±55.23)μg/L,有显著差异(P<0.05)。PGR分别为4.09±2.15和8.95±5.18,显著差异(P<0.05);以PGⅠ≤70μg/L且PGR≤3.0为界值来计算诊断慢性萎缩性胃炎的敏感性和特异性分别为72.3%和93.3%。结论检测血清PG及PGR可用于慢性萎缩性胃炎的筛查,如有异常,应进一步行胃镜检查以确诊并指导治疗。     

应用前列腺素E1治疗慢性肾功不全的临床观察

目的探讨前列腺素E1治疗慢性肾功能不全的疗效。方法将CRF患者随机分为治疗组和对照组,治疗组静点前列腺素E1(凯时)15d,其余治疗方法与对照组相同,测治疗前后血肌酐值及24h尿量进行统计学分析。结果治疗组患者经静脉滴注前列腺素E1(凯时)15d后,血肌酐水平下降,24h尿量增多。结论前列腺素E1能改善CRF患者的肾功能,保护残余肾功能。     

Plasma vaspin concentrations are decreased in acute coronary syndrome,but unchanged in patients without coronary lesions

Objective

Previous studies suggested that decreased serum vaspin levels were associated with coronary artery disease (CAD). The present study aimed to investigate the association between plasma vaspin levels and different states of CAD.

Design and methods

A total of 162 patients with coronary angiography (CAG) proved that CAD was enrolled. Additional 103 patients complained with “chest discomfort” with negative CAG, and 60 normal subjects were enrolled in this study. The levels of plasma vaspin, adiponectin, clinical parameters, lipid profile and C reactive protein (CRP) were measured.

Results

The levels of plasma vaspin were significantly lower in the CAD group (0.47 ± 0.63 μg/L) than those in the healthy group and CAG (−) group (all p < 0.001). In CAD group, the pos hoc analysis showed that serum vaspin concentration in acute myocardial infarction group (0.21 ± 0.19 μg/L) was significantly lower than that in the unstable angina pectoris group (0.40 ± 0.37 μg/L) (p = 0.012), and serum vaspin concentration in unstable angina pectoris was significantly lower than that in stable angina pectoris group (0.92 ± 0.94 μg/L) (p = 0.013). The plasma vaspin concentration was also negatively correlated with the severity of CAD (1-vessel: 0.86 ± 0.90 μg/L; 2-vessel: 0.36 ± 0.39 μg/L; 3-vessel: 0.21 ± 0.16 μg/L). The plasma vaspin concentration in CAG (−) group with “chest discomfort” (1.93 ± 2.57 μg/L) was similar to the healthy control group (2.18 ± 3.49 μg/L).

Conclusions

The plasma vaspin concentration correlated to the severity of CAD. Furthermore, plasma vaspin has a value of avoiding patients without CAD from unnecessary CAG.     

Anti-inflammatory effects of hydroalcoholic extract and two biflavonoids from Garcinia gardneriana leaves in mouse paw oedema

Garcinia gardneriana (Planch. & Triana) Zappi (Clusiaceae) is widely distributed in Brazil and used in folk medicine to treat inflammation, pain, and urinary tract and other infections. However, very few studies have analyzed these therapeutic effects. In this study, the anti-inflammatory effects of the hydroalcoholic extracts from Garcinia gardneriana (HEGG) and some of its isolated biflavonoids were evaluated. The results showed that HEGG from the leaves, bark and seeds reduced carrageenan-induced mouse paw inflammation, in addition to diminishing the myeloperoxidase activity in the stimulated tissues. The reduction of neutrophil infiltration by treatment with the HEGG from leaves was confirmed by histology. The leaf extract also reduced the paw oedema evoked by bradykinin, histamine, prostaglandin E2 and 12-O-tetradecanoylphorbol acetate. However, it partially decreased substance P and compound 48/80-caused paw oedema, without any influence on the arachidonic acid-induced oedema. Both of the isolated compounds, fukugetin and GB-2a, prevented the carrageenan-induced paw oedema. In conclusion, this study showed important anti-inflammatory effects of HEGG through its interaction with different intracellular signaling pathways, without interfering with the formation of arachidonic acid (AA) metabolites. These characteristics, in addition to the wide distribution and culturing ease of the plant, confirm its popular use and highlight its promise in the development of new anti-inflammatory drugs.     

阴道放置米索前列醇及卡孕栓在早期人工流产术前的应用

目的:评价米索前列醇(简称米索)及卡孕栓在早期妊娠人工流产术前阴道用药的宫颈扩张作用。方法:400μg米索或1mg卡孕栓被术前2～5小时分别放置妊娠5～10周妇女阴道后穹窿内,记录每例患者宫颈的扩张程度及腹痛、出血等副作用。结果:当药物作用3.5小时以内时,两组宫颈扩张作用的差异尚不明显。3.5小时后卡孕栓扩张宫颈的作用则明显优于米索。阴道内术前用药超过3.5小时无论米索组或卡孕栓组与其自身比较,宫颈扩张的作用均较用药3.5小时以内的作用明显提高。卡孕栓组较米索组腹痛等胃肠道副反应的发生率高。结论:米索及卡孕栓在早期妊娠人工流产术前阴道用药有较强的宫颈扩张作用。米索副作用相对较少,适于人工流产前的宫颈扩张的常规用药。妊娠天数较长,胚胎较大,人流手术相对困难者使用卡孕栓较为合理。上述药物术前阴道使用推荐时间为至少3.5小时。     

米非司酮和PG联用终止早孕的宫内超声图象及临床处理

本文通过对６８例年龄２２～３５岁，停经８４～５４天，应用米非司酮和ＰＧ终止妊娠的妇女，因用药后未见妊娠囊排出或因出血较多而作的子宫Ｂ超检查，概括并描述了药流后继续妊娠、妊娠囊及蜕膜组织官腔内滞留的超声图象，并提出了相应的处理原则。我们认为，在米非司酮和ＰＧ联合终止早孕的临床中应用Ｂ超监护，对减少并发症具有重要意义。     

Systematically applied chemicals that damage lung tissue

A large, and increasing number of drugs and chemicals have been found which are toxic to lung following systemic administration. These agents damage lung tissue specifically, or in addition to damage to other tissues. Mechanisms explaining the pulmonary damage produced by some lung toxins have been uncovered. These include concentration of the agent within lung, the absence of adequate pulmonary detoxication systems, and bioactivation to a toxic species within specific lung cells or at distant sites followed by transport to the lung. The basic biochemical lesions underlying lung damage, responses of individual lung cells and pulmonary repair processes to the toxic agent, and species and age differences in susceptibility to lung damage have not, however, been well defined for most lung toxins. This review describes the information available on pulmonary biochemical and pathological changes associated with some of these lung-toxic agents. In addition, mechanisms proposed to explain the lung damage are discussed. The agents covered include: paraquat, the thioureas, butylated hydroxytoluene, the trialkylphosphorothioates, various lung-toxic furans and antineoplastic agents, the pyrrolizidine alkaloids, metals and organometallic compounds, amphiphilic agents, hydrocarbons, oleic acid, 3-methylindole, and diabetogenic agents. Detailed reviews on the overall toxicity of many of these agents have been published elsewhere. This review concentrates on their pulmonary toxicity. Information is presented as an overview to illustrate both the extensive literature that is available and the important questions that remain to be answered about systemic chemicals that damage lung tissue.