Fluorine-18 labeling of three novel D-peptides by conjugation with N-succinimidyl-4-[18F]fluorobenzoate and preliminary examination by postmortem whole-hemisphere human brain autoradiography

Introductionβ-Amyloid (Aβ) plaques and neurofibrillary tangles are the main characteristics of Alzheimer's disease (AD). Positron emission tomography (PET), a high-resolution, sensitive, and noninvasive imaging technique, has been widely utilized in visualizing the localization of plaques and tangles and thereby distinguishing between AD and healthy controls. A small 12-mer d-enantiomeric peptide (amino acid sequence=QSHYRHISPAQV), denoted as D1, has high binding affinity to Aβ in vitro in the sub-micromolar range, and consequently, its radiolabeled analogues have a potential as radioligands for visualizing amyloid plaques in vivo by PET.AimThe aims of the present work were to develop three different potent D1 derivative peptides labeled with fluorine-18 and to examine them in the AD and control postmortem human brain by autoradiography (ARG).MethodsThree different D1 derivative peptides were radiolabeled with fluorine-18 ([¹⁸F]ACI-87, [¹⁸F]ACI-88, [¹⁸F]ACI-89) using the prosthetic group N-succinimidyl-4-[¹⁸F]fluorobenzoate ([¹⁸F]SFB) and purified by high performance liquid chromatography (HPLC). Preliminary ARG measurements were performed in AD and control brains.ResultsThe three fluorine-18-labeled d-peptides were obtained in a total synthesis time of 140 min with radiochemical purity higher than 98%. The specific radioactivities of the three different D1 derivative peptides were between 9 and 113 GBq/μmol. ARG demonstrated a higher radioligand uptake in the cortical gray matter and the hippocampus in the AD brain as compared to age-matched control brain.ConclusionsFluorine-18 labeling of the three novel D1 derivative peptides using [¹⁸F]SFB was successfully accomplished. Higher contrast between AD and control brain slices demonstrates their potential applicability for further use in vivo by PET.     

Dual behavior of HCV Core gene in regulation of apoptosis is important in progression of HCC

Hepatitis C virus (HCV) causes acute and chronic hepatitis which can lead to HCC (Hepatocelluar carcinoma) via oxidative stress, steatosis, insulin resistance, fibrosis and liver cirrhosis. Apoptosis is essential for the control and eradication of viral infections. In acute HCV infection, enhanced hepatocyte apoptosis is significant for elimination of viral pathogen. In case of chronic HCV, down regulation of apoptosis and enhanced cell proliferation not only causes HCV infection persistency in the majority of patients. However, the impact of apoptosis in chronic HCV infection is not well understood. It may be harmful by triggering liver fibrosis, or essential in interferon (IFN) induced HCV elimination. Regulation of apoptosis in hepatocytes by HCV Core is so important in progression of HCC. This review focuses on the dual character of HCV Core on regulation of apoptosis and progression of HCC.     

Evaluation of a Cornstarch-Based Ultrasound Gel Alternative for Low-Resource Settings

Background

Ultrasound is an ideal imaging modality for low-resource settings given its portability, ease of use, and wide range of applications. Commercially available ultrasound gels may be unavailable or cost prohibitive in low-resource settings.

Objective

Our aim was to investigate the quality of images obtained with an alternative ultrasound gel made from cornstarch and water in comparison with commercially available gel.

Methods

The cornstarch gel was made by heating water and cornstarch. The gel was used to obtain standard ultrasound images of the gallbladder, kidneys, bladder, heart, and neck vessels by the study investigators. Commercial gel was used as the control. Twenty-four ultrasound clips were shown to four blinded radiologists and two ultrasound-fellowship−trained emergency department physicians. They rated the images on adequacy (yes/no) and graded the images detail, resolution, and quality using a continuous 0−10 scale.

Results

A total of 144 video clips were shown to reviewers and 129 data-collection sheets were returned. There was no statistical difference in the proportion of images deemed to be of adequate quality: cornstarch-based gel = 0.97 (95% confidence interval [CI] 0.92−1.00) vs. commercially available gel = 0.85 (95% CI 0.75−0.94) (p = 0.053). The cornstarch gel was superior to commercial gel on all three image parameters: detail (p = 0.002), resolution (p = 0.018), and quality (p = 0.013).

Conclusions

In this study, a gel made from cornstarch and water was an acceptable coupling medium and provided equally adequate images as compared with commercial ultrasound gel. This inexpensive gel made from ubiquitous materials can be an acceptable alternative to commercial gel in low-resource settings.     

Effects of dietary weight loss on obstructive sleep apnea: a meta-analysis

Purpose

Clinical and epidemiologic investigations suggest a strong association between obesity and obstructive sleep apnea (OSA). The purpose of this study is to evaluate the currently available literature reporting on the effectiveness of dietary weight loss in treating OSA among obese patients.

Methods

Relevant studies were identified by computerized searches of PubMed, EMBASE, CINAHL, Web of Science, and The Cochrane Central Register of Controlled Trials through September 2011 as well as the reference lists of all obtained articles. Information on study design, patient characteristics, pre- and post-dietary weight loss measures of OSA and body mass index (BMI), and study quality was obtained. Data were extracted by two independent analysts. Weighted averages using a random-effects model are reported with 95 % confidence intervals.

Results

Nine articles representing 577 patients were selected. Dietary weight loss program resulted in a pooled mean BMI reduction of 4.8 kg/m² (95 % confidence interval [CI] 3.8-5.9). The random-effects pooled apnea hypopnea (AHI) indices at pre- and post-dietary intervention were 52.5 (range 10.0–91.0) and 28.3 events/h (range 5.4–64.5), respectively (p?<?0.001). Compared to control, the weighted mean difference of AHI was decreased by ?14.3 events/h (95 % CI ?23.5 to ?5.1; p?=?0.002) in favor of the dietary weight loss programs.

Conclusions

Dietary weight loss programs are effective in reducing the severity of OSA but not adequate in relieving all respiratory events. Weight reduction programs should be considered as adjunct rather than curative therapy.