Rejuvenation: Turning Back Time by Enhancing CISD2.

The aging human population with age-associated diseases has become a problem worldwide. By 2050, the global population of those who are aged 65 years and older will have tripled. In this context, delaying age-associated diseases and increasing the healthy lifespan of the aged population has become an important issue for geriatric medicine. CDGSH iron-sulfur domain 2 (CISD2), the causative gene for Wolfram syndrome 2 (WFS2; MIM 604928), plays a pivotal role in mediating lifespan and healthspan by maintaining mitochondrial function, endoplasmic reticulum integrity, intracellular Ca2+ homeostasis, and redox status. Here, we summarize the most up-to-date publications on CISD2 and discuss the crucial role that this gene plays in aging and age-associated diseases. This review mainly focuses on the following topics: (1) CISD2 is one of the few pro-longevity genes identified in mammals. Genetic evidence from loss-of-function (knockout mice) and gain-of-function (transgenic mice) studies have demonstrated that CISD2 is essential to lifespan control. (2) CISD2 alleviates age-associated disorders. A higher level of CISD2 during natural aging, when achieved by transgenic overexpression, improves Alzheimer's disease, ameliorates non-alcoholic fatty liver disease and steatohepatitis, and maintains corneal epithelial homeostasis. (3) CISD2, the expression of which otherwise decreases during natural aging, can be pharmaceutically activated at a late-life stage of aged mice. As a proof-of-concept, we have provided evidence that hesperetin is a promising CISD2 activator that is able to enhance CISD2 expression, thus slowing down aging and promoting longevity. (4) The anti-aging effect of hesperetin is mainly dependent on CISD2 because transcriptomic analysis of the skeletal muscle reveals that most of the differentially expressed genes linked to hesperetin are regulated by hesperetin in a CISD2-dependent manner. Furthermore, three major metabolic pathways that are affected by hesperetin have been identified in skeletal muscle, namely lipid metabolism, protein homeostasis, and nitrogen and amino acid metabolism. This review highlights the urgent need for CISD2-based pharmaceutical development to be used as a potential therapeutic strategy for aging and age-associated diseases.

Andrographolide suppresses the malignancy of triple-negative breast cancer by reducing THOC1-promoted cancer stem cell characteristics.

Triple-negative breast cancers (TNBCs) are difficult to cure and currently lack of effective treatment strategies. Cancer stem cells (CSCs) are highly associated with the poor clinical outcome of TNBCs. Thoc1 is a core component of the THO complex (THOC) that regulates the elongation, processing and nuclear export of mRNA. The function of thoc1 in TNBC and whether Thoc1 serves as a drug target are poorly understood. In this study, we demonstrated that thoc1 expression is elevated in TNBC cell lines and human TNBC patient tissues. Knockdown of thoc1 decreased cancer stem cell populations, reduced mammosphere formation, impaired THOC function, and downregulated the expression of stemness-related proteins. Moreover, the thoc1-knockdown 4T1 cells showed less lung metastasis in an orthotopic breast cancer mouse model. Overexpression of Thoc1 promoted TNBC malignancy and the mRNA export of stemness-related genes. Furthermore, treatment of TNBC cells with the natural compound andrographolide reduced the expression of Thoc1 expression, impaired homeostasis of THOC, suppressed CSC properties, and delayed tumor growth in a 4T1-implanted orthotopic mouse model. Andrographolide also reduced the activity of NF-κB, an upstream transcriptional regulator of Thoc1. Notably, thoc1 overexpression attenuates andrographolide-suppressed cellular proliferation. Altogether, our results demonstrate that THOC1 promotes cancer stem cell characteristics of TNBC, and andrographolide is a potential natural compound for eliminating CSCs of TNBCs by downregulating the NF-κB-thoc1 axis.

Interactions between Obstructive Sleep Apnea Syndrome Severity, Obesity, Sex Difference and Attention-Deficit/Hyperactivity Disorder on Health-Related Quality of Life: A Non-Interventional Prospective Observational Study.

Obstructive sleep apnea syndrome (OSAS) severity, obesity, sex difference, and attention-deficit/hyperactivity disorder (ADHD) had a complex impact on health-related quality of life (HRQoL). However, the interactive effects among these features on HRQoL remained to be clarified. This study aimed to investigate the individual and interactive associations between the four characteristics of interest and HRQoL as determined by 36-Item Short Form Health Survey, Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). This non-interventional, prospective, observational study enrolled a total of 132 patients with suspected OSAS for analysis. While OSAS severity and ADHD detected by adult ADHD Self-Report Scale, termed as screened ADHD, interact with each other, all the four studied features were individually associated with HRQoL. After adjusting for potential physiological and polysomnographic confounders, screened ADHD was independently correlated with PSQI > 5 (OR = 4.126, 95% CI, 1.490−11.424), mental component score < 50 (OR = 5.873, 95% CI, 2.262−15.251) and ESS > 10 (OR = 3.648, 95% CI, 1.738−7.657). Our results show that ADHD detection is necessary and should be incorporated into clinical practice for OSAS management.

TREM-2 mediates dendritic cell-induced NO to suppress Th17 activation and ameliorate chronic kidney diseases.

Chronic kidney disease (CKD) is a global public health issue. CKD is caused by the infiltration of various myeloid cell types into renal tissue, resulting in renal fibrosis and tubular atrophy. Unilateral ureteral obstruction (UUO) surgery in mice is a model of CKD and characterized by high expression of the anti-inflammatory receptor, Triggering receptor expressed on myeloid cells 2 (TREM-2), on myeloid cells in affected kidneys. Here, we show that iNOS expression and nitric oxide (NO) induction were decreased in Trem-2-/- bone marrow-derived DCs (BMDCs) and in Trem-2 knockdown DC2.4 cells stimulated in vitro with LPS. The nitration of RORγt was decreased in T cells co-cultured with LPS-stimulated Trem-2-/- BMDCs, enhancing IL-17 production. UUO-treated Trem-2-/- mice displayed aggravated renal pathogenesis accompanied by greater neutrophil infiltration and enhanced Th17 cells differentiation, phenotypes that could be rescued by the administration of L-arginine (a biological precursor of NO). Our data identify a key mechanism underlying TREM-2-mediated NO to modulate the cellular crosstalk between dendritic cells, Th17, and neutrophils. Furthermore, we also reveal TREM-2 as a potential novel target for the development of anti-inflammatory drugs in CKD treatment. KEY MESSAGES: The expression of TREM-2 is increased in nephritis TREM-2+ DCs maintain NO production to negatively regulate Th17 differentiation The severe pathologies of nephritis can be rescued by L-arginine supplementation.

Vaccine adjuvant activity of a TLR4-activating synthetic glycolipid by promoting autophagy.

Toll-like receptors (TLRs) play crucial roles in host immune defenses. Recently, TLR-mediated autophagy is reported to promote immune responses via increasing antigen processing and presentation in antigen presenting cells. The present study examined whether the synthetic TLR4 activator (CCL-34) could induce autophagy to promote innate and adaptive immunity. In addition, the potential of CCL-34 as an immune adjuvant in vivo was also investigated. Our data using RAW264.7 cells and bone marrow-derived macrophages showed that CCL-34 induced autophagy through a TLR4-NF-κB pathway. The autophagy-related molecules (Nrf2, p62 and Beclin 1) were activated in RAW264.7 cells and bone marrow-derived macrophages under CCL-34 treatment. CCL-34-stimulated macrophages exhibited significant antigen-processing activity and induced the proliferation of antigen-specific CD4+T cells as well as the production of activated T cell-related cytokines, IL-2 and IFN-γ. Furthermore, CCL-34 immunization in mice induced infiltration of monocytes in the peritoneal cavity and elevation of antigen-specific IgG in the serum. CCL-34 treatment in vivo did not cause toxicity based on serum biochemical profiles. Notably, the antigen-specific responses induced by CCL-34 were attenuated by the autophagy inhibitor, 3-methyladenine. In summary, we demonstrated CCL-34 can induce autophagy to promote antigen-specific immune responses and act as an efficient adjuvant.

Andrographolide and its potent derivative exhibit anticancer effects against imatinib-resistant chronic myeloid leukemia cells by downregulating the Bcr-Abl oncoprotein.

Chronic myelogenous leukemia (CML) is clinically treated with imatinib, which inhibits the kinase activity of the Bcr-Abl oncoprotein. However, imatinib resistance remains a common clinical issue. Andrographolide, the major compound of the medicinal plant Andrographis paniculata, was reported to exhibit anticancer activity. In this study, we explored the therapeutic potential of andrographolide and its derivative, NCTU-322, against both imatinib-sensitive and imatinib-resistant human CML cell lines. Both andrographolide and NCTU-322 downregulated the Bcr-Abl oncoprotein in imatinib-resistant CML cells through an Hsp90-dependent mechanism similar to that observed in imatinib-sensitive CML cells. In addition, NCTU-322 had stronger effects than andrographolide on downregulation of Bcr-Abl oncoprotein, induction of Hsp90 cleavage and cytotoxicity of CML cells. Notably, andrographolide and NCTU-322 could induce differentiation, mitotic arrest and apoptosis of both imatinib-sensitive and imatinib-resistant CML cells. Finally, the anticancer activity of NCTU-322 against imatinib-resistant CML cells was demonstrated in vivo. In summary, our data demonstrated that andrographolide and NCTU-322 inhibit Bcr-abl function via a mechanism different from that of imatinib, and they induced multiple anticancer effects in both imatinib-sensitive and resistant CML cells. Our findings demonstrate that andrographolide and NCTU-322 are potential therapeutic agents again CML.

A New Method for Self-Estimation of the Severity of Obstructive Sleep Apnea Using Easily Available Measurements and Neural Fuzzy Evaluation System.

This paper proposes a neural fuzzy evaluation system (NFES) with significant variables selected from stepwise regression to predict apnea-hypopnea index (AHI) for evaluating obstructive sleep apnea (OSA). The variables considered are the change statuses of blood pressure (BP) before going to sleep and early in the morning as well as other five easily available measurements (age, body mass index (BMI), etc.) so that users can use the system for self-evaluation of OSA. A total of 150 subjects are reviewed retrospectively and categorized as training (120 subjects) and validation (30 subjects) sets by a fivefold cross-validation scheme with stratified sampling based on the OSA severity. Among the eight variables, the stepwise regression shows that BMI, the difference of systolic BP, and Epworth Sleepiness Scale were the significant factors to predict AHI. The three variables are fed as inputs to the NFES with interpretable fuzzy rules automatically generated from the training set. The average accuracy, sensitivity (Sn), specificity (Sp), and Sn+Sp-1 of the NFES were 75.6%, 77.2%, 75.0%, and 0.552, respectively, in distinguishing the OSA level of normal-mild (AHI <15) from moderate-severe (AHI ≱ 15), and outperformed the stepwise regression, back-propagation neural network, and support vector machine models. In addition to personal self-estimation, physicians could differentiate the two OSA levels by means of the fast-screening system for both outpatients and inpatients.

Improvement in the Grain Growth of Plasma-Treated Nano-Sized ZnO Films and Their Characterization.

The well-aligned ZnO nanorods were rapidly grown on an indium tin oxide (ITO)-coated glass substrate using Al-doped ZnO (AZO) thin film as seed layer by the microwave-assisted hydrothermal chemical route. The optimal growth conditions for the well-aligned ZnO nanorods were obtained by modulating H2 plasma pretreatment time for the seed layer and synthesis time for ZnO nanorods. The H2 plasma effect of the seed layer on the alignment, growth rate and crysallinity of ZnO nanods is also demonstrated. The synthesized ZnO nanorods were annealed in atmosphere of N2, O2 and H2 + N2 mixed gas to improve the related physical characteristics, the ZnO nanorods on grapheme/ITO substrate were also investigated. The results show that the alignment and growth rate of ZnO nanorods depends on the physical characteristics and roughness of the seed layer, which can be improved by H2 plasma pretreatment. The average growth rate of ZnO nanorods synthesized by microwave hydrothermal technique is about 2.2 µm/hr which significantly superior to other conventional techniques. After the appropriate N2 annealing treatment, good quality and well-aligned ZnO nanorods, which are single crystal with stacking defects and pyramid or candle shape, were obtained. A fundamental model of the effect of H2 plasma pretreatment on the surface of seed layer and the growth of ZnO nanorods using a microwave-assisted hydrothermal chemical route is also described.

Effects of Kuan-Sin-Yin decoction on immunomodulation and tumorigenesis in mouse tumor models.

BACKGROUND: Complementary therapies are widely used among cancer patients. Kuan-Sin-Yin (KSY) decoction, a popular qi-promoting herbal medicine, was constituted with several herbs known to exhibit immunomodulating or anticancer activity. After combining these herbs as a compound formula, it is necessary to reassess the immunomodulation effects, the effects on tumor growth, and possible toxicity of KSY. METHODS: The anti-cancer effects of KSY in vivo were determined by measuring the tumor volumes, anticancer-associated cytokines (IFN-gamma, TNF-alpha, IL-2, and IL-12), accumulation of tumor infiltrating leukocytes (TILs), proliferation and apoptosis-related molecular markers (Ki-67, p53, p21, activated caspase 3, and cleaved PARP), and an in situ TUNEL assay. The body weight and serum chemistry of treated mice were also assessed. In vitro, the effects of KSY were evaluated using MTT assay, BrdU incorporation assay and cell growth curve. RESULTS: In vivo, KSY suppressed bladder or lung cancer growth but did not promote the production of cytokines nor increase the accumulation of TILs. The expression of p53 and p21 in KSY-treated mice were increased. The numbers of apoptotic tumor cells and the expression of apoptosis marker proteins (Caspase 3 and cleaved PARP) were not significantly elevated after KSY treatment. In vitro, the viability and proliferation of tumor cells, but not normal cells, were suppressed by KSY treatment. No significant toxicity was found in KSY-treated mice. CONCLUSIONS: KSY suppressed the tumor growth in vivo and in vitro, which resulted from its cytostatic effects on cancer cells, rather than the induction of anti-cancer immunity. Under these experimental conditions, no apparent toxicity was observed.

Double right coronary artery and its clinical implications.

Congenital anomalies of the coronary arteries are present in 0.2-1.4% of the general population. These anomalies represent one of the most confusing issues in the field of cardiology and challenges for interventional cardiologists and cardiac surgeons if the anomalies are unrecognised. Double right coronary artery is one of the rarest coronary arteries. Previously, the probability of developing atherosclerotic changes in patients with a double right coronary artery was considered to be equal to that in those without it. In reality, however, a high prevalence of atherosclerotic coronary artery disease was found in patients with a double right coronary artery originating from a single ostium after our comprehensive literature search through the PubMed database. Owing to the fact that double right coronary artery is both a congenital and potentially atherosclerotic coronary artery disease at diagnosis, coronary intervention or cardiac operation is more complicated than previously believed. Individuals with a double right coronary artery may be unaware of its presence until an accidental finding during coronary angiography or cardiac operation and are at risk for unsuspected complications of atherosclerotic coronary artery disease or during cardiac operation. Therefore, it is important to obtain information on the anatomic variants of this congenital coronary anomaly in patients who are undergoing either coronary intervention, aortic root operation or myocardial revascularisation. To our knowledge, this is the first comprehensive article to discuss the anomalies and their clinical implications.

Acute aortic dissection type A with acute coronary involvement: a novel classification.

BACKGROUND: Acute coronary involvement (ACI) due to acute aortic dissection (AAD) type A is potentially fatal. We examined selected patients with AAD type A, which had evolved over 14 years, and acute coronary involvement. The purpose of this study was to determine the characteristics of patients with ACI due to AAD type A. METHODS: Between 1997 and 2011, we recruited 20 patients (14.1%) with ACI (14 men, 6 women; mean age: 51.8 ± 11.8 years; age range: 35-79 years) from 142 patients who had undergone surgical repair of AAD type A. RESULTS: We propose a novel 4-category classification scheme based on the surgical pathological findings. The right coronary artery was involved in 15 patients, and the left was involved in 5 patients. Fourteen patients had preoperative myocardial ischemia. In the other 6 patients, acute coronary involvement was found intraoperatively. Patients with ACI were significantly younger than those without ACI (51.8 ± 11.8 vs. 61.0 ± 11.8; p = 0.001), a lower prevalence of intramural hematoma (5.0% vs. 32.8%; p = 0.011), a higher aortic regurgitation rate (95.0% vs. 53.5%; p = 0.001). Patients presenting with ACI had an in-hospital mortality rate of 20.0% (4/20), while those without ACI had an in-hospital mortality rate of 19.7% (24/122). CONCLUSIONS: Acute coronary involvement due to AAD type A is not always associated with coronary malperfusion. Patients with ACI were much younger, had a higher aortic regurgitation rate, and, less commonly, had intramural hematoma. This new classification scheme would make it more convenient for surgeons to decide on treatment options for this special cohort.

Double right coronary artery or split right coronary artery?

The prevalence of congenital anomalies of the coronary arteries (CAAs) is reported to be approximately 0.2-1.4% of the general population. Of them, The double right coronary artery (RCA) is one of the rarest coronary anomalies. Nonetheless, there is no consensus of the definition of a double RCA until now. Several concepts have been proposed in order to define what is and is not a double RCA. So far, it was been reported 37 times and in 44 cases after a comprehensive literature search through the PubMed database, using the keywords "double right coronary artery," "duplicated right coronary artery," "dual right coronary artery" and "split right coronary artery." Most of the published articles (28 of 37 articles) used the name "double right coronary artery." Nevertheless, some investigators contended that a split RCA is anatomically the same anomaly as the improperly named "double right coronary artery". The debate between those who favor "double RCA" and those who favor "split RCA" indicate the need for a consensus regarding the nomenclature as well diagnostic criteria of such coronary anomalies. It is the time we need to reach a consensus of the nomenclature of this congenital coronary anomaly.

Rare anatomic entity of quadricuspid aortic valve with aortic insufficiency: a case report.

Quadricuspid aortic valve (QAV) is a rare congenital heart defect that often causes symptomatic aortic insufficiency in adulthood, imposing valve replacement. Herein, we describe one unusual case of QAV which underwent valve replacement uneventfully.

Evaluating the prevalence of silent coronary artery disease in asymptomatic patients with spinal cord injury.

To evaluate the prevalence of coronary artery disease (CAD) in patients with spinal cord injury (SCI), 47 clinically asymptomatic SCI patients received thallium-201 myocardial perfusion single photon emission computed tomography (Tl-201 SPECT) after dipyridamole administration for the diagnosis of CAD. There were 4 groups as follows; group 1: 13 patients with quadriplegia and complete SCI, group 2: 11 patients with quadriplegia and incomplete SCI, group 3: 11 patients with paraplegia and complete SCI, and group 4: 12 patients with paraplegia and incomplete SCI. There were no significant differences in sex distribution, ages, SCI duration, or CAD risk factors among the SCI patients in the 4 groups. All Tl-201 SPECT images were interpreted by the agreement of 2 experienced nuclear medicine physicians without prior knowledge of the patients' histories. A total of 30 of 47 (63.8%) SCI patients had abnormal Tl-201 SPECT findings. Among the 4 groups of SCI patients, those in groups 1 and 4 had the significantly highest and lowest prevalences of abnormal Tl-201 SPECT findings, respectively. We concluded that combined quadriplegia and complete SCI is an important CAD risk factor in SCI patients based on the objective evidence of intravenous dipyridamole cardiac stress testing with Tl-201 SPECT.

Effects of angiotensin II-receptor blockers on soluble cell adhesion molecule levels in uncomplicated systemic hypertension: An observational, controlled pilot study in Taiwanese adults.

BACKGROUND: Controversy exists as to whether individuals with hypertension without risk factors for atherosclerosis (eg, diabetes mellitus, dyslipidemia. OBJECTIVE: The aim of this study was to determine whether (1) levels of solubleCAMs (sCAMs) (soluble E-selectin [sE-selectin], soluble intercellular adhesion molecule-1 [sICAM-1 ], soluble vascular cell adhesion molecule-1 [sVCAM-1 ], and von Willebrand factor [vWF]) are elevated in Taiwanese adults with uncomplicated essential hypertension without other risk factors; (2) CAM levels increase with severity (stage) of hypertension; and (3) monotherapy with the angiotensin II-receptor blocker (ARB) irbesartan modulates CAM expression in a subgroup of these patients. METHODS: This observational, controlled pilot study was conducted at the Hypertension Clinic, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Adult patients with uncomplicated essential hypertension without other risk factors (eg, diabetes mellitus, dyslipidemia, obesity) and normotensive controls were eligible. Blood pressure (BP) was determined using 24-hour ambulatory BP monitoring (ABPM) in all participants, and the staging of hypertension was classified based on criteria in The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (normotensive, prehypertension, stage I hypertension, and stage II hypertension). The SCAM levels and 24-hour ABPM were measured before and after 8 weeks of open-label irbesartan monotherapy in a subgroup of the patients with hypertension. Patients who had difficulty achieving the target BP values on irbesartan monotherapy were treated with combination therapy (2 or 3 antihypertensive agents); levels of sCAMs were not measured in these patients. Plasma levels of sE-selectin, the sCAMs, and vWF were measured using enzyme-linked immunosorbent assay. RESULTS: The study comprised 61 patients with uncomplicated essentialhypertension (33 men and 28 women; mean [SD] age, 51 [12] years) and 17 normotensive controls (11 men, 6 women; mean [SD] age, 52 [ 11 ] years). The mean (SD) dose of irbesartan was 243 (63) mg. Hypertensive patients had significantly higher circulating levels of sICAM-1 compared with normotensive controls (P = 0.009). No significant differences in levels of sVCAM-1, sE-selectin, or vWF were found between hypertensive patients and controls. The mean sICAM-1 level was significantly higher in the prehypertensive patients compared with normotensive controls (P = 0.03). The mean sE-selectin level was significantly higher in the patients with stage I hypertension compared with the prehypertensive group (P = 0.01). The 18 patients given 8 weeks of irbesartan monotherapy showed a significant decrease from baseline in systolic and diastolic BP (both, P = 0.001) and sE-selectin (P= 0.006), but not in sVCAM-1 or sICAM. Forty-three patients did not reach target BP on irbesartan monotherapy and thus were treated with combination therapy. CONCLUSIONS: Based on the results of this observational, controlled pilotstudy in Taiwanese patients, we suggest that ARB therapy, in addition to reducing BP, has the potential to suppress CAM expression and to improve endothelial dysfunction in hypertension.

Effect of leukocyte depletion on endothelial cell activation and transendothelial migration of leukocytes during cardiopulmonary bypass.

BACKGROUND: Although leukocyte depletion from systemic circulation during cardiopulmonary bypass (CPB) has been studied, the effect of leukocyte depletion on the leukocyte-endothelial cascade remains poorly understood. So far, there has been no published work on the effects of leukocyte filters during cardiac operations from the viewpoint of endothelial activation and transendothelial neutrophil migration. METHODS: Thirty-two patients undergoing elective heart operations were randomly allocated to a leukocyte-depletion (LD) group or a control group. Blood samples were collected at seven time points: before sternotomy, at 30 minutes and at 60 minutes of CPB, at 5 minutes after coronary reperfusion, at the end of CPB, and at 2 hours and 24 hours after the cessation of CPB. The plasma concentrations of P-selectin, intercellular adhesion molecule-1 (ICAM-1), interleukin-8, and platelet-endothelial cell adhesion molecule-1 (PECAM-1) were measured using enzyme-linked immunosorbent assays. Plasma malondialdehyde (MDA) concentration was determined by measurement of thiobarbituric acid-reactive substances in plasma. In addition, blood samples collected at intervals before and after operation were used for arterial blood gases. RESULTS: Our studies show significant increases of plasma levels of P-selectin, ICAM-1, interleukin-8, PECAM-1, and MDA during and after CPB in the control group. Interestingly, a significant decrease of plasma levels of P-selectin, ICAM-1, interleukin-8, PECAM-1, and MDA, and better preservation of lung function could be found in the LD group compared with the control group. CONCLUSIONS: Our results demonstrate a rationale for using a leukocyte filter in patients undergoing cardiac surgery to attenuate the endothelial-mediated component of the CPB-induced inflammatory response by reducing endothelial activation and neutrophil transmigration.

Usefulness of thallium-201 muscle perfusion scan to investigate perfusion reserve in the lower limbs of Type 2 diabetic patients.

This study evaluated the usefulness of thallium-201 muscle perfusion scan (Tl-201 muscle scan) to investigate perfusion reserve in the lower limbs of asymptomatic Type 2 diabetic patients without peripheral ischemia findings. Tl-201 muscle scan was carried out in 36 diabetic male patients with Type 2 diabetes mellitus of more than 10 years in duration who had no evidence of peripheral arterial disease in their history, physical examination, or Doppler ultrasonography. A control group consisted of 24 healthy age-matched nondiabetic men. Each subject flexed their right foot maximally both dorsally and plantar 60 times. In the middle of this exercise, 2mCi Tl-201 was injected intravenously. Three minutes after the injection, a posterior image of both calves was obtained using a gamma camera. Rectangular regions of interest (ROIs) were symmetrically drawn over both calves. The total count (Ct) in the resting calf was subtracted from the Ct in the exercising calf, and the percentage increase, termed the perfusion reserve, was determined. A significant difference was found between the perfusion reserves of the Type 2 diabetic patients and control groups (70.2+/-10.7% and 98.6+/-9.4%, respectively; P<.05). In conclusion, the perfusion reserve in the lower limb muscles in Type 2 diabetic patients may be measured by Tl-201 muscle perfusion scan.

Usefulness of technetium-99m sestamibi myocardial perfusion SPECT in detection of cardiovascular involvement in patients with systemic lupus erythematosus or systemic sclerosis.

The main purpose of the study was to evaluate the utility of technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography (Tc-99m sestamibi SPECT) in detection of cardiac involvement in systemic lupus erythematosus (SLE) or systemic sclerosis (SS) patients. Fifty SLE or SS female patients with cardiac symptom/sign such as chest discomfort and/or dyspnea and/or occasionally palpitation and 50 SLE or SS female patients without any cardiac symptom/sign were investigated using Tc-99m sestamibi SPECT during rest and stress after dipyridamole infusion. Twenty-five age- and sex-matched healthy females were also included as controls in this study. The results of Tc-99m sestamibi SPECT were classified into four types including normal, persistent perfusion defect (PD), reversible perfusion defect (RD), and reverse perfusion defect (RR). The results of Tc-99m sestamibi SPECT in the 25 healthy females were normal. Perfusion abnormalities were detected in 44/50 (88%) symptomatic SLE or SS patients. However, myocardial perfusion abnormalities were only detected in 19/50 (38%) asymptomatic SLE or SS patients (P value<0.05 by a chi2 test). However, for risk factor of coronary artery disease and abnormal resting EKG, the incidences were not significant between symptomatic and asymptomatic patients (P values >0.05 by a chi2 test). Tc-99m sestamibi SPECT is a useful noninvasive imaging modality to detect cardiac involvement in symptomatic or asymptomatic SLE or SS patients.