Change of coronary flow velocity during the cold pressor test is related to endothelial markers in subjects with chest pain and a normal coronary angiogram

Background:

Several studies demonstrated that endothelial or atherosclerotic biomarkers, including plasma free insulin‐like growth factor‐I(IGF‐I), soluble CD40 ligand (sCD40L), adiponectin, and leptin have an influence on coronary endothelial function.

Hypothesis:

The aim of the present study was to investigate whether change of coronary flow velocity of the distal left anterior descending artery (LAD) during the cold pressor test (CPT) with transthoracic Doppler echocardiography (TTE) was associated with these biomarkers in subjects with chest pain and a normal coronary angiogram.

Methods:

In 190 subjects (mean age, 54±11 years; male:female, 113:77) with chest pain and a normal coronary angiogram, peak diastolic velocity (PDV) of the distal LAD during the CPT with TTE was assessed. Acetylcholine provocation test was performed in 58 subjects (mean age, 51±10 years) who were clinically suspected of vasospasm. CPT%PDV was defined as the percent change in PDV during the CPT. Associations between CPT%PDV and clinical parameters were analyzed.

Results:

According to multiple regression analysis, CPT%PDV was associated with plasma free IGF‐I in the entire study population (β=0.295, P<0.001 in all subjects; β=0.341, P=0.001 in males; β=0.243, P=0.037 in females; β=0.303, P=0.002 in nonsmokers; and β=0.256, P=0.047 in smokers), and sCD40L in males (β=?0.269, P=0.008)and smokers (β=?0.261, P=0.046). Subjects with vasospasm to intracoronary acetylcholine had lower plasma free IGF‐I(6.9±3.3 vs 8.9±3.4, P=0.026) and CPT%PDV (8.8±24.9 vs 52.7±26.0, P<0.001) than the others. Plasma adiponectin and leptin were not associated with CPT%PDV.

Conclusions:

Change of coronary flow velocity assessed using the CPT with TTE may be related to endothelial markers, especially plasma free IGF‐I. © 2011 Wiley Periodicals, Inc. Additional Supporting Information may be found in the online version of this article. The authors have no funding, financial relationships, or conflicts of interest to disclose.

     

Which symptoms can distinguish between subjective cognitive impairment (SCI) and mild cognitive impairment (MCI)?

The SCI, the MCI, and the Alzheimer's disease (AD) are on a spectrum of disease progression; therefore, identification of the earliest signs of cognitive deterioration is becoming a crucial issue. The goal of this study was to examine symptom characteristics and distinguish predictive symptoms in patients with MCI compared with SCI, using caregiver questionnaires. We assessed the Korean Dementia Screening Questionnaire (KDSQ) and Seoul Instrumental activities of Daily Living (S-IADL) of 344 subjects with SCI and 697 with MCI. Multivariate logistic regression analyses were conducted after adjusting for age, sex, and educational status. Common and rare symptoms were similar between the SCI and MCI groups. The most distinguishing features of KDSQ were 'Finds it hard to go somewhere on his/her own using public transportation' (odds ratio=OR=4.56, p<0.0001), 'Has difficulty in operating appliances' (OR=2.47, p=0.001), and 'Keeps repeating the same question' (OR=2.03, p<0.0001). In S-IADL, the most outstanding features were 'using household appliances' (OR=3.99, p<0.0001), 'taking medication' (OR=2.38, p=0.01), and 'using public transportation' (OR=1.94, p=0.04). The dysfunction in 'using household appliance' and 'using public transportation' reflect the possibility of MCI rather than SCI. Therefore, it is suggested that these symptoms also have a discriminative and predictive power in identifying SCI.     

Exploiting PI3K/mTOR signaling to accelerate epithelial wound healing

The molecular circuitries controlling the process of skin wound healing have gained new significant insights in recent years. This knowledge is built on landmark studies on skin embryogenesis, maturation, and differentiation. Furthermore, the identification, characterization, and elucidation of the biological roles of adult skin epithelial stem cells and their influence in tissue homeostasis have provided the foundation for the overall understanding of the process of skin wound healing and tissue repair. Among numerous signaling pathways associated with epithelial functions, the PI3K/Akt/mTOR signaling route has gained substantial attention with the generation of animal models capable of dissecting individual components of the pathway, thereby providing a novel insight into the molecular framework underlying skin homeostasis and tissue regeneration. In this review, we focus on recent findings regarding the mechanisms involved in wound healing associated with the upregulation of the activity of the PI3K/Akt/mTOR circuitry. This review highlights critical findings on the molecular mechanisms controlling the activation of mTOR, a downstream component of the PI3K–PTEN pathway, which is directly involved in epithelial migration and proliferation. We discuss how this emerging information can be exploited for the development of novel pharmacological intervention strategies to accelerate the healing of critical size wounds.     

Construction of a Tissue‐Engineered Annulus Fibrosus

The intervertebral disc is composed of load‐bearing fibrocartilage that may be subjected to compressive forces up to 10 times the body weight. The multilaminated outer layer, the annulus fibrosus (AF), is vulnerable to damage and its regenerative potential is limited, sometimes leading to nuclear herniation. Scaffold‐based tissue engineering of AF using stem cell technology has enabled the development of bi‐laminate constructs after 10 weeks of culture. It is difficult to know if these constructs are limited by the differentiation state of the stem cells or the culture system. In this study, we have characterized an expandable scaffold‐free neoconstruct using autologous AF cells. The construct was prepared from pellet cultures derived from monolayer cultures of AF cells from mature pigs that became embedded in their own extracellular matrix. The pellet cultures were incubated for 24 h in a standardized conical tube and then carefully transferred intact to a culture flask and incubated for 21 days to allow continued matrix synthesis. Cell viability was maintained above 90% throughout the culture period. The engineered scaffold‐free construct was compared with the native AF tissue by characterization of gene expression of representative markers, histological architecture, and biochemical composition. The morphological and biochemical characteristics of the cultured disc construct are very similar to that of native AF. The cell number per gram of construct was equal to that of native AF. Expression of aggrecan was elevated in the engineered construct compared with RNA extracted from the AF. The glycosaminoglycan content in the engineered construct showed no significant difference to that from native construct. These data indicate that scaffold‐free tissue constructs prepared from AF cells using a pellet‐culture format may be useful for in vitro expansion for transplantation into damaged discs.     

Correction: Self-assembled fibrillar networks comprised of a naturally-occurring cyclic peptide—LOB3

Correction for ‘Self-assembled fibrillar networks comprised of a naturally-occurring cyclic peptide—LOB3’ by M. A. Rogers et al., RSC Adv., 2016, 6, 40765–40776.

The authors regret the omission of the following conflict of interest statement.Dr Martin J. T. Reaney is the founder of, and has an equity interest in, Prairie Tide Diversified Inc. (PTD, Saskatoon, SK, Canada: previous company name is Prairie Tide Chemicals Inc.). Dr Youn Young Shim is a Market Consultant for PTD in Korea. The terms of this arrangement have been reviewed and approved by the University of Saskatchewan in accordance with its conflict of interest policies.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.