Mucoadhesive Polymers in Peroral Peptide Drug Delivery. VI. Carbomer and Chitosan Improve the Intestinal Absorption of the Peptide Drug Buserelin In Vivo

Purpose. To evaluate the effect of the crosslinked poly(acrylate) carbomer 934P (C934P) and its freeze-dried neutralized sodium salt (FNaC934P) as well as chitosan hydrochloride on the intestinal absorption of the peptide drug buserelin. Methods. Buserelin was applied intraduodenally in control buffer, 0.5% (w/v) C934P, 0.5% (w/v) FNaC934P, 1.5% (w/v) chitosan hydrochloride or FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture in rats. Results. All polymer preparation showed a statistically significant improvement of buserelin absorption compared to the control solution. The absolute bioavailabilities for the different polymer preparations were: control, 0.1%; 0.5% FNaC934P, 0.6%; 0.5% C934P, 2.0%; chitosan hydrochloride, 5.1% and FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture, 1.0%. The higher bioavailability with chitosan hydrochloride compared to C934P and FNaC934P indicates that for buserelin the intestinal transmucosal transport enhancing effect of the polymer plays a more dominant role than the protection against proteases such as -chymotrypsin. Conclusions. The mucoadhesive polymers carbomer 934P and chitosan hydrochloride are able to enhance the intestinal absorption of buserelin in vivo in rats, and may therefore be promising excipients in peroral delivery systems for peptide drugs.     

Complications of Penile Lengthening and Augmentation Seen at 1 Referral Center

Purpose

Complications of the recent cosmetic technique of penile lengthening and girth enhancement are reviewed.

Materials and Methods

During a 16-month period 12 men presented with complications of penile augmentation performed elsewhere. All 12 patients had undergone release of the suspensory ligament and 10 had received autologous fat injection.

Results

the chief complaint was poor cosmetic appearance (irregular residual fat nodules in 7 men, skin deformity and scarring in 4 and scrotalization in 4). Reoperation was necessary in 6 patients, wound complications occurred in 6 and sexual dysfunction was reported by 4. Only 1 patient reported a subjective increase in penile length.

Conclusions

Although a verifiable complication rate may never by available, the morbidity of elective penile lengthening and girth enhancement is noteworthy. These cosmetic techniques should be regarded as experimental.     

CT and MRI Findings in a Child with Constrictive Pericarditis

Constrictive pericarditis is rare in children. We report computed tomography (CT) and magnetic resonance imaging (MRI) findings in a 3-year-old girl. She had a swollen abdomen that increased in two months. CT and MRI showed a thickened pericardium (5.2 mm) without calcification. Both atria were enlarged and ventricles were relatively small. The engorged inferior vena cava had 2.8× the diameter of the descending aorta at the same level. Symptoms were dramatically improved after pericardiectomy. The histopathological features confirmed chronic pericarditis.     

Psychological,endocrine and neural responses to social evaluation in subclinical depression

This study aimed to identify vulnerability patterns in psychological, physiological and neural responses to mild psychosocial challenge in a population that is at a direct risk of developing depression, but who has not as yet succumbed to the full clinical syndrome. A group of healthy and a group of subclinically depressed participants underwent a modified Montreal Imaging Stress task (MIST), a mild neuroimaging psychosocial task and completed state self-esteem and mood measures. Cortisol levels were assessed throughout the session. All participants showed a decrease in performance self-esteem levels following the MIST. Yet, the decline in performance self-esteem levels was associated with increased levels of anxiety and confusion in the healthy group, but increased levels of depression in the subclinical group, following the MIST. The subclinical group showed overall lower cortisol levels compared with the healthy group. The degree of change in activity in the subgenual anterior cingulate cortex in response to negative evaluation was associated with increased levels of depression in the whole sample. Findings suggest that even in response to a mild psychosocial challenge, those individuals vulnerable to depression already show important maladaptive response patterns at psychological and neural levels. The findings point to important targets for future interventions.     

艾灸对动脉粥样硬化小鼠炎性反应因子及MMP-9的实验研究

目的:观察艾灸对Apo E~(-/-)小鼠主动脉内肿瘤坏死因子(TNF-α)、白细胞介素-10(IL-10)及基质金属蛋白酶9(MMP-9)的影响,并从抑制炎性反应,稳定动脉粥样硬化斑块等角度探讨艾灸在防治动脉粥样硬化中的机制。方法:将48只采用高脂饮食喂养的载脂蛋白E基因敲除小鼠(Apo E~(-/-)小鼠)作为动脉粥样硬化模型,并随机分为3组:艾灸组,模型组,药物对照组。并将16只同龄相同遗传背景的C57BL/6小鼠作为空白对照组。空白组、模型组小鼠每天常规抓取、固定,并放置假艾灸装置。艾灸组小鼠每天抓取固定,并艾灸膻中穴。药物组小鼠每天采用辛伐他汀0.28 mg/100 g灌胃,所有干预20 min/d,6 d/周,干预14周后牺牲,取材检测。Elisa法测定主动脉内TNF-α、IL-10、MMP-9的含量。油红"O"染色观察胸主动脉病理改变。结果:1)与模型组相比,艾灸组,药物组小鼠主动脉内TNF-α、MMP-9含量明显降低(P0.05),艾灸组,药物组之间无明显差异;与模型组相比,药物组IL-10水平明显升高有统计学意义(P0.05),艾灸组小鼠主动脉内IL-10呈升高趋势,但无统计学意义。2)胸主动脉病理改变:与空白组相比,模型组胸主动脉可见明显的AS斑块,内膜破坏,中膜增厚,平滑肌细胞破坏变性,管腔变狭窄。相比于模型组,艾灸组及药物组主动脉病变明显减轻。结论:1)艾灸可以有效缓解动脉粥样硬化病变,抑制动脉粥样硬化斑块生长;2)艾灸可以抑制体内炎性反应,并具有稳定斑块的作用     

Receptor for advanced glycation endproduct modulators: a new therapeutic target in Alzheimer’s disease

Introduction: Reduction in the deposition of amyloid β (Aβ) has been the primary target for Alzheimer’s disease (AD) therapeutics recently, but in clinical trials this approach has generally been unsuccessful. A common feature of AD pathology is a complex inflammatory component that could be a target for treatment. One feature of this inflammation has been the involvement of the receptor for advanced glycation endproducts (RAGE), whose ligands include advanced glycation-endproduct-modified proteins as well as lipids and Aβ, which are found at elevated levels in AD brains.

Areas covered: In this article, the authors describe the key features of RAGE and how it could have a role in AD pathogenesis. They also summarize experimental animal and clinical data that demonstrate the therapeutic effect of RAGE inhibition and consider what these findings mean for human disease.

Expert opinion: RAGE has multiple ligands, including Aβ, that are increased in AD brains. Inhibiting RAGE-ligand interactions without activating receptor signaling can reduce multiple pathological pathways relevant for AD. Several RAGE inhibitors and modulators are now being tested as therapeutics for AD. Recent Phase II studies have established the good safety and tolerability of TTP448 with some evidence of positive benefit at lower dose. This suggests that further studies are required.     

Pasteurella multocida Septicemia and Peritonitis in a Patient with Cirrhosis: Case Report and Review of the Literature

A case of Pasteurella multocida septicemia and peritonitis in a patient with cirrhosis is reported and the literature reviewed. Patients with cirrhosis and exposure to domestic animals are at risk for this infection. Initial empiric therapy of spontaneous bacterial peritonitis in such patients should include a penicillin to which this organism is usually susceptible.     

高重力加速度及其模拟条件下脑电变化研究综述

高重力加速度及其模拟条件下脑电变化的相关研究在航空医学领域具有重要意义。本文综合介绍了飞行中＋Gz和离心机＋Gz作用、下体负压作用、不同程度缺氧、短暂意识丧失下的脑电变化特点及其相互之间的关系。国内外学者围绕＋Gz及其模拟条件下的脑电变化规律已取得一定研究成果,但在脑电的定量分析,以及利用脑电对＋Gz加速度引起的短暂意识丧失进行前驱预警等方面的研究尚待深入。本文为高重力加速度环境下的脑电变化特征研究提供重要参考依据,对探寻利用脑电预警高重力加速度引起的意识丧失具有现实意义。     

A new method of measuring the stiffness of corpus cavernosum penis with ShearWave? Elastography

Objective:

To evaluate the feasibility of measuring the stiffness of corpus cavernosum penis (CCP) with ShearWave™ Elastography (SWE; SuperSonic Imagine, Aix-en-Provence, France).

Methods:

40 healthy volunteers with ages ranging from 19 to 81 years (mean, 36 years; standard deviation, 17 years) were selected in this study. The ultrafast ultrasound device Aixplorer^® (SuperSonic Imagine) was used for the research and the probe selected was SuperLinear™ SL15-4 (SuperSonic Imagine). The shear wave stiffness (SWS) of CCP was measured using SWE images. The measurement indexes of SWS included (1) SWS of CCP measured in the transverse section (SWS-T), (2) SWS of CCP measured in the longitudinal section (SWS-L) and (3) mean of SWS-T and SWS-L (SWS-M). The interval between hormone test and SWE examination of each subject was less than 7 days. The paired t-test was used to analyse the differences between SWS-T and SWS-L. The Pearson correlation was used to analyse the correlation of SWS of CCP with age as well as with sex hormone levels.

Results:

There was no significant difference between SWS-T and SWS-L (p > 0.05). SWS (SWS-T, SWS-L, SWS-M) was negatively correlated with age and oestradiol value, and SWS (SWS-T, SWS-L, SWS-M) was positively correlated with testosterone value.

Conclusion:

SWE could serve as a new non-invasive method of evaluating the stiffness of CCP.

Advances in knowledge:

It is the first time that we have discussed the feasibility of measuring the stiffness of CCP with SWE and analysed the correlation of SWS of CCP with age as well as with sex hormone levels.ShearWave™ Elastography (SWE; SuperSonic Imagine, Aix-en-Provence, France) is a new ultrasound technology that could be used to assess tissue stiffness in clinic and is currently the only elastography technology certified by the US Food and Drug Administration. This technology makes it possible to quantify the tissue stiffness accurately. Unlike early elastography methods, which rely on manual compression and measuring tissue displacement, SWE requires no manual compression, and it uses ultrasonic pulse to make the tissue generate shear waves. A real-time SWE map is produced by detection of shear wave velocity and colour coding. Since the propagation speed of the shear wave is determined by the stiffness of tissue, the real-time SWE map could be used to measure the overall and local stiffness of tissue exactly. Studies have shown that this technology could be used to evaluate the stiffness of intravital tissue accurately.^1–3Furthermore, SWE is a safe, non-ionizing and non-invasive technique that has the same thermal and mechanical energy as conventional Doppler imaging. It is applicable to the examination of human reproductive organs. The tissue structure of corpus cavernosum penis (CCP) has important impact on the stiffness of CCP. Therefore, the stiffness of CCP could be used as an index for assessing the tissue structure of CCP. At the same time, the tissue structure of CCP has important impact on the erectile function. So, it is of great clinical significance to measure the stiffness of CCP.The stiffness of CCP is closely associated with age.⁴ Previous pathological studies have indicated that, with increase in age, sinusoids in CCP gradually decrease, occlusion and fibrosis occur, the smooth muscle cells also atrophy and decrease gradually. These changes in tissue structure and composition of CCP can directly lead to the change of its stiffness. The stiffness of CCP is also associated with sex hormone levels. Testosterone can promote the generation of smooth muscle cells and enhance cell vitality in CCP. Cell vitality and generation of smooth muscle cells in CCP decline with testosterone decrease, which can lead to cell atrophy and reduction in their number and consequently a change of stiffness of CCP.^5–7However, at present, no accurate and non-invasive method can be used to assess stiffness of CCP in clinic. In this study, we evaluated the feasibility of measuring stiffness of CCP with SWE by analysing the correlation of the stiffness value of CCP with age as well as sex hormone levels.