Safety and efficacy of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with critical limb ischemia.

VM202, a plasmid DNA that expresses two isoforms of hepatocyte growth factor, may elicit angiogenic effects that could benefit patients with critical limb ischemia (CLI). In a phase 2, double-blind trial in 52 CLI patients, we examined the safety and potential efficacy of intramuscular injections of low-dose (n=21) or high-dose (n=20) VM202 or placebo (n=11) in the affected limb (days 0, 14, 28 and 42). Adverse events and serious adverse events were similar among the groups; no malignancy or proliferative retinopathy was seen.

Erratum to: Genetically-controlled Vesicle-Associated Membrane Protein 1 expression may contribute to Alzheimer's pathophysiology and susceptibility.

Following publication of this work, we noticed that we inadvertently failed to include Dr Ferenc Deák in the author list. The author list has now been corrected and the amended authors' contributions section has been modified accordingly below.

Targeting autophagy in cancer management - strategies and developments.

Autophagy is a highly regulated catabolic process involving lysosomal degradation of intracellular components, damaged organelles, misfolded proteins, and toxic aggregates, reducing oxidative stress and protecting cells from damage. The process is also induced in response to various conditions, including nutrient deprivation, metabolic stress, hypoxia, anticancer therapeutics, and radiation therapy to adapt cellular conditions for survival. Autophagy can function as a tumor suppressor mechanism in normal cells and dysregulation of this process (ie, monoallelic Beclin-1 deletion) may lead to malignant transformation and carcinogenesis.

Electrical Stimulation of Vascular Autonomic Nerves: Effects on Heart Rate, Blood Pressure, and Arrhythmias.

Background: Recent clinical studies have shown conflicting results of the efficacy of renal sympathetic denervation (RSD) to mitigate hypertension. In this study, we compared electrical stimulation (ES) of autonomic nerves on the surface of the left pulmonary artery (LPA) and renal arteries (RAs) on heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), and cardiac arrhythmias.

Methods: In 16 pentobarbital anesthetized dogs, standard electrocardiography leads and blood pressure (BP) were continuously recorded.

Results of a prospective, multicenter study evaluating quality of life, safety, and efficacy of sacral neuromodulation at twelve months in subjects with symptoms of overactive bladder.

Aims: This prospective, multicenter post-approval study evaluated the success rate of sacral neuromodulation (SNM) with the InterStim® System at 12-months. Subjects with bothersome symptoms of overactive bladder (OAB) including urinary urge incontinence (UI) or urgency-frequency (UF), who failed at least one anticholinergic medication and had at least one not tried were included.

Methods: Subjects with successful test stimulation received an SNM implant.

Validation of a survey tool assessing effectiveness of an educational intervention on the caring behaviors and referral activities of community pharmacists for migraineurs.

Background: Community pharmacists are in an ideal position to ameliorate migraineur under-consulting, under-diagnosis, and under-treatment. Contemporary education/training on developing therapeutic alliances with patients and in advanced pharmacotherapy may further motivate pharmacists to impact the care of migraineurs.

Objectives: The objectives of this study were to assess pharmacists' perceptions of a migraine training program and their self-assessment of subsequent impact on patient care and to develop and assess a tool evaluating the impact of the training program from the patients' perspectives: (1) for patients diagnosed with migraines - identify perceptions of care by pharmacists who have undergone specialty training in migraine vs.

Deficiency in LRP6-mediated Wnt signaling contributes to synaptic abnormalities and amyloid pathology in Alzheimer's disease.

Alzheimer's disease (AD) is an age-related neurological disorder characterized by synaptic loss and dementia. The low-density lipoprotein receptor-related protein 6 (LRP6) is an essential coreceptor for Wnt signaling, and its genetic variants have been linked to AD risk. Here we report that neuronal LRP6-mediated Wnt signaling is critical for synaptic function and cognition.

Salivary proteins may be useful for determining caries susceptibility.

Article Title And Bibliographic Information: Salivary proteins as a biomarker for dental caries-A systematic review. Martins C, Buczynski AK, Maia LC, Siqueira WL, Castro GF. J Dent 2013; 41(1): 2-8.

Impaired vascular endothelial growth factor A and inflammation in patients with peripheral artery disease.

We compared apoptosis, cellular oxidative stress, and inflammation of cultured endothelial cells treated with sera from 130 patients with peripheral artery disease (PAD) and a control group of 36 patients with high burden of comorbid conditions and cardiovascular risk factors. Second, we compared circulating inflammatory, antioxidant capacity, and vascular biomarkers between the groups. The groups were not significantly different (P > .

Novel computerized health risk appraisal may improve longitudinal health and wellness in primary care: a pilot study.

Objectives: Health Risk Appraisals (HRAs) have been implemented in a variety of settings, however few studies have examined the impact of computerized HRAs systematically in primary care. The study aimed at the development and pilot testing of a novel, comprehensive HRA tool in primary care practices.

Methods: We designed, implemented and pilot tested a novel, web-based HRA tool in four pair-matched intervention and control primary care practices (N = 200).

Aging-induced dysregulation of dicer1-dependent microRNA expression impairs angiogenic capacity of rat cerebromicrovascular endothelial cells.

Age-related impairment of angiogenesis is likely to play a central role in cerebromicrovascular rarefaction and development of vascular cognitive impairment, but the underlying mechanisms remain elusive. To test the hypothesis that dysregulation of Dicer1 (ribonuclease III, a key enzyme of the microRNA [miRNA] machinery) impairs endothelial angiogenic capacity in aging, primary cerebromicrovascular endothelial cells (CMVECs) were isolated from young (3 months old) and aged (24 months old) Fischer 344 × Brown Norway rats. We found an age-related downregulation of Dicer1 expression both in CMVECs and in small cerebral vessels isolated from aged rats.

Aging exacerbates obesity-induced oxidative stress and inflammation in perivascular adipose tissue in mice: a paracrine mechanism contributing to vascular redox dysregulation and inflammation.

Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner.

Circulating factors induced by caloric restriction in the nonhuman primate Macaca mulatta activate angiogenic processes in endothelial cells.

Moderate caloric restriction (CR) without malnutrition increases healthspan in virtually every species studied, including nonhuman primates. In mice, CR exerts significant microvascular protective effects resulting in increased microvascular density in the heart and the brain, which likely contribute to enhanced tolerance to ischemia and improved cardiac performance and cognitive function. Yet, the underlying mechanisms by which CR confer microvascular protection remain elusive.

Testing predictions of the oxidative stress hypothesis of aging using a novel invertebrate model of longevity: the giant clam (Tridacna derasa).

Bivalve species with exceptional longevity are newly introduced model systems in biogerontology to test evolutionarily conserved mechanisms of aging. Here, we tested predictions based on the oxidative stress hypothesis of aging using one of the tropical long-lived sessile giant clam species, the smooth giant clam (Tridacna derasa; predicted maximum life span: >100 years) and the short-lived Atlantic bay scallop (Argopecten irradians irradians; maximum life span: 2 years). The warm water-dwelling giant clams warrant attention because they challenge the commonly held view that the exceptional longevity of bivalves is a consequence of the cold water they reside in.

Malignant melanoma of the vulva: an extension of cutaneous melanoma?

Objective: To determine the prognostic significance of the 2002 revisions of the American Joint Committee on Cancer (AJCC) Staging System for cutaneous melanoma in melanoma of the vulva and review the current surgical utilized for treatment of this neoplasm.

Methods: Demographic, surgical and outcomes data were obtained from the records of vulvar melanoma patients treated from 1990 to 2006 at five academic medical centers. The 2002 modifications of the AJCC staging system for cutaneous melanoma, Breslow thickness and Clark level, were applied to all subjects.

Emotional and biological stress measures in Katrina survivors relocated to Oklahoma.

Objectives: The authors assessed relocated Hurricane Katrina survivors' emotional and biological stress measures 20 months postdisaster to understand effects of both hurricane exposure and forced relocation on emotional and physical health.

Design: Psychiatric diagnoses, post-traumatic stress disorder (PTSD) and depressive symptoms, and biological stress measures were compared for total survivor and control groups and subgroups by PTSD diagnoses and lifetime trauma.

Setting: Outpatient university psychiatry clinics in Oklahoma City and Tulsa.

Targeted therapies for gynecologic malignancies.

Despite the enormous promise that targeted therapies hold for patients with gynecologic malignancies, it is far too early to recommend any targeted therapy outside of a clinical trial. There remains considerable work to be done before targeted therapies will have a significant role in this patient population. We have learned that different tumor types express different targets, but that the mere expression of a target does not necessarily correlate with benefit from the use of the targeted agent.

Associations of postmenopausal hormone therapy with markers of hemostasis and inflammation and lipid profiles in diabetic and nondiabetic american Indian women: the strong heart study.

Objectives: To examine the associations of postmenopausal hormone therapy (PHT) with indicators of hemostasis and inflammation and with lipid profiles in American Indian women and to determine if diabetes modifies these associations.

Methods: This report is a cross-sectional analysis of data from 1446 postmenopausal women who were free from cardiovascular disease (CVD) at the second Strong Heart Study examination (1993-1995). Diabetes was diagnosed by WHO criteria.

Estimating means of a set of measures from small samples by using multivariate composite estimating concept-the Strong Heart Study.

In this study, we describe a method employing the multivariate composite estimating (MCE) concept to estimate the means of a set of measurements based on small samples from different groups in a population as well as the grand means of the measurements for the population. The advantages of these estimators over simple averages used in the literature are that they have lower mean squared errors, and they improve on simple averages by taking account of variations and correlations among the set of measurements as well as differences among groups. An application to the Strong Heart Study baseline exam data is provided.

[The coupling of canine ventricular myocyte beta2-adrenoceptors to L-type calcium current].

Unlabelled: To establish the functional coupling of beta adrenoceptor (beta AR) subtypes of beta 1AR and beta 2AR to L-type calcium current (ICaL), we investigated the non-selective agonist isoproterenol (ISO), and the relatively selective beta 2AR agonists zinterol (ZIN) and salbutamol (SAL) on ICaL in isolated canine ventricular myocytes in the presence and absence of CGP 20712A (CGP) and atenolol (AT), selective beta 1AR antagonists, and ICI 118,551 (ICI) a selective beta 2AR antagonist. Peak ICaL was determined using "patch type" microelectrodes and whole cell voltage clamp. ISO (0.

CNS location of uterine-related neurons revealed by trans-synaptic tracing with pseudorabies virus and their relation to estrogen receptor-immunoreactive neurons.

Retrograde, transneuronal tracing with Bartha's strain of pseudorabies virus was used in rats to identify spinal cord, brainstem and hypothalamic loci of uterine-related neurons that could function in the regulation of uterine activity. Based on the premise that estrogen might influence such uterine-related neurons, the existence of estrogen receptors in neurons in these same loci was examined. Viral injections were made into the uterine cervix, body and cervical end of the uterine horns, and the rats allowed to survive for four to six days.

The stability of ethanol in human whole blood controls: an interlaboratory evaluation.

Sterile whole human blood control materials were commercially prepared in batches containing anticoagulants and preservatives and approximately 90, 150, and 230 mg/dL ethanol with and without 0.3% (w/v) sodium azide. Aliquots in sealed vials were stored by the manufacturer at 2-8 degrees C until shipped monthly to three academic toxicology laboratories that analyzed them in duplicate by gas chromatographic headspace methods at monthly intervals for one year.

Localization of estrogen receptor protein and estrogen receptor messenger RNA in peripheral autonomic and sensory neurons.

The presence of estrogen receptor protein and estrogen receptor messenger RNA was revealed in peripheral ganglionic neurons of the rat. The pelvic parasympathetic autonomic ganglion and lumbosacral dorsal root sensory ganglia were examined for estrogen receptor-containing neurons because they have known projections to the uterus and uterine cervix. The vagal nodose ganglia were studied for estrogen receptor-containing neurons because they are suspected sources of influence on the uterus.

Management of patients with chronic stable angina at low risk for serious cardiac events.

Successful management of the patient with chronic stable angina requires correct stratification by assessing the risk of future coronary events. Patients at low risk for such events have a relatively good prognosis; revascularization procedures (balloon angioplasty or surgery) offer no benefit over medical management. Such patients should be offered medical therapy as their first option.