The relationships among monocyte subsets,miRNAs and inflammatory cytokines in patients with acute myocardial infarction

Background

Acute myocardial infarction (AMI) causes irreversible myocardial damage and release of inflammatory mediators, including cytokines, chemokines and miRNAs. We aimed to investigate changes in the levels of cytokines (IL-6, TNF-α and IL-10), miRNAs profiles (miR-146 and miR-155) and distribution of different monocyte subsets (CD14++CD16-, CD14++CD16+, CD14+CD16++) in the acute and post-healing phases of AMI.

MIM1 induces COLO829 melanoma cell death through mitochondrial membrane breakdown,GSH depletion,and DNA damage

Malignant melanoma is a high aggressive malignancy in humans and causes 60–80% of deaths from skin cancer. Defect in an intrinsic pathway of apoptosis via overexpression of Mcl-1 is responsible for malignant melanoma development and progression, and also for resistance to chemotherapeutic agents. MIM1 is a specific low molecular Mcl-1 protein inhibitor that is able to induce Mcl-1-dependent cancer cells death. Here, we examined the effect of MIM1 as well as MIM1 and dacarbazine (DTIC) mixture on cell viability, apoptosis, and cell cycle progression in COLO829 melanoma cells. Cell viability was performed by the WST-1 assay. Analysis of apoptosis as well as cell cycle progression was determined by fluorescence image cytometer NucleoCounter NC-3000. The obtained results demonstrated that the MIM1 exhibited high cytotoxicity against melanotic melanoma cells and induced mitochondrial membrane breakdown, GSH depletion, and DNA fragmentation. Additionally, MIM1 enhanced the proapoptotic effect of DTIC toward melanoma cells; furthermore, a mixture of these drugs caused cell cycle arrest at G2/M phase in COLO829 cells. Taken together, these data provide, for the first time, evidence that a low molecular weight Mcl-1 inhibitor—MIM1 may be a promising agent with antitumor and proapoptotic properties toward melanoma cells.     

Targeting Corticotropin‐Releasing Factor Projections from the Oval Nucleus of the Bed Nucleus of the Stria Terminalis Using Cell‐Type Specific Neuronal Tracing Studies in Mouse and Rat Brain

The bed nucleus of the stria terminalis (BNST) is known to play a critical role in mediating the behavioural and autonomic responses to stressors. The oval nucleus of the BNST (BNSTov) contains cell bodies that synthesise the stress hormone corticotropin‐releasing factor (CRF). Although afferent fibres originating from the BNSTov have been shown to innervate several key structures of the neuroendocrine and central autonomic system, the question remains as to whether some of these fibres are CRF‐positive. To directly address this question, we injected a ‘floxed’ anterograde tracer (rAAV5/EF1a‐DIO‐mCherry) into the BNSTov of CRFp3.0Cre^GFP transgenic mice, which express a green fluorescent protein (GFP) under the control of the CRF promoter. Serial sections were then analysed for the presence of double‐labelled fibres in potential projection sites. To determine whether CRF neurons in the rat BNSTov send comparable projections, we infused rat BNSTov with an adeno‐associated viral vector (AAV) in which the human synapsin promoter drives enhanced GFP expression. We then used CRF immunoreactivity to examine double‐labelled fluorescent fibres and axon terminals in projection sites from brain sections of the AAV‐infused rats. We have observed several terminal fields in the mouse and rat brain with double‐labelled fibres in the Dorsal raphe nucleus (DRD), the paraventricular nucleus of the hypothalamus and, to a lesser extent, in the ventral tegmental area. We found double‐labelled terminal boutons in the nucleus accumbens shell, prelimbic cortex and posterior basolateral nucleus of the amygdala. The most intense double‐labelling was found in midbrain, including substantia nigra pars compacta, red nucleus, periaqueductal grey and pontine nuclei, as well as DRD. The results of the present study indicate that CRF neurons are the output neurons of the BNSTov and they send projections not only to the centres of neuroendocrine and autonomic regulation, but also regions modulating reward and motivation, vigilance and motor function, as well as affective behaviour.     

Diagnostic Accuracy of Contrast-Enhanced Computed Tomography and Positron Emission Tomography With 18-FDG in Identifying Malignant Solitary Pulmonary Nodules

Contrast-enhanced computed tomography (CECT) and positron emission tomography with 18-FDG (FDG-PET/CT) are used to identify malignant solitary pulmonary nodules. The aim of the study was to evaluate the accuracy of CECT and FDG-PET/CT in diagnosing the etiology of solitary pulmonary nodule (SPN).Eighty patients with newly diagnosed SPN >8 mm were enrolled. The patients were scheduled for either or both, CECT and FDG-PET/CT. The nature of SPN (malignant or benign) was determined either by its pathological examination or radiological criteria.In 71 patients, the etiology of SPN was established and these patients were included in the final analysis. The median SPN diameter in these patients was 13 mm (range 8–30 mm). Twenty-two nodules (31%) were malignant, whereas 49 nodules were benign.FDG-PET/CT was performed in 40 patients, and CECT in 39 subjects. Diagnostic accuracy of CECT was 0.58 (95% confidence interval [CI] 0.41–0.74). The optimal cutoff level discriminating between malignant and benign SPN was an enhancement value of 19 Hounsfield units, for which the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CECT were 100%, 37%, 32%, and 100%, respectively. Diagnostic accuracy of FDG-PET/CT reached 0.9 (95% CI 0.76–0.9). The optimal cutoff level for FDG-PET/CT was maximal standardized uptake value (SUV max) 2.1. At this point, the sensitivity, specificity, PPV, and NPV were 77%, 92%, 83%, and 89%, respectively.The diagnostic accuracy of FDG-PET/CT is higher than that of CECT. The advantage of CECT is its high sensitivity and negative predictive value.     

The oxytocin/vasopressin receptor family has at least five members in the gnathostome lineage, inclucing two distinct V2 subtypes

The vertebrate oxytocin and vasopressin receptors form a family of G-protein-coupled receptors (GPCRs) that mediate a large variety of functions, including social behavior and the regulation of blood pressure, water balance and reproduction. In mammals four family members have been identified, three of which respond to vasopressin (VP) named V1A, V1B and V2, and one of which is activated by oxytocin (OT), called the OT receptor. Four receptors have been identified in chicken as well, but these have received different names. Until recently only V1-type receptors have been described in several species of teleost fishes. We have identified family members in several gnathostome genomes and performed phylogenetic analyses to classify OT/VP-receptors across species and determine orthology relationships. Our phylogenetic tree identifies five distinct ancestral gnathostome receptor subtypes in the OT/VP receptor family: V1A, V1B, V2A, V2B and OT receptors. The existence of distinct V2A and V2B receptors has not been previously recognized. We have found these two subtypes in all examined teleost genomes as well as in available frog and lizard genomes and conclude that the V2A-type is orthologous to mammalian V2 receptors whereas the V2B-type is orthologous to avian V2 receptors. Some teleost fishes have acquired additional and more recent gene duplicates with up to eight receptor family members. Thus, this analysis reveals an unprecedented complexity in the gnathostome repertoire of OT/VP receptors, opening interesting research avenues regarding functions such as regulation of water balance, reproduction and behavior, particularly in reptiles, amphibians, teleost fishes and cartilaginous fishes.     

Acute infarction of the left ventricular papillary muscle: Electrocardiographic pattern and recognition of its location

Background and hypothesis: ST-segment depression during acute myocardial infarction (AMI) is known to herald serious hemodynamic complications. Since the mechanism of this dependence is not clear, we reinvestigated the old concept of papillary muscle infarction (PMI) as a cause of marked ST depression. Methods: Autopsies and morpho-electrocardiographic correlations were performed in 53 patients with AMI involving one or both left ventricular papillary muscles, and in 10 patients with AMI, but without acute PMI. Results: ST-segment depression ≥l mm in at least two leads (mean 3.6 ± 2.2 mm) was found in 46 (86.8%) patients with, and in one without acute PMI. Thus, the sensitivity and specificity in selecting patients with acute PMI from among those with AMI were 86.8 and 90%, respectively, with an overall accuracy of diagnosis of acute PMI in the course of AMI of 87.3%. Among 26 patients with ST elevation consistent with diagnosis of AMI, ST depression, recorded in 22 patients, was insignificantly greater than in 24 of 27 patients without ST elevation: 4.1 ± 2.9 versus 3.1 ± 1.2 mm. Localization of ST depression in the limb leads allowed recognition of which papillary muscle suffered from acute infarction: ST depression in the inferior leads was seen only in patients with anterolateral PMI, whereas in leads I and/or aVL it was seen only in cases with posteromedial PMI. This rule was also valid in patients without concomitant ST elevation. Conclusion: Patients with acute PMI show marked ST-segment depression. Its location in the limb leads allows recognition of which papillary muscle has undergone necrosis. This cause of marked ST depression in patients with AMI may explain the high mortality in this particular group.     

Responsiveness of the reproductive axis to a single missed evening meal in young adult males

Objectives: The male reproductive axis is responsive to energetic deficits, including multiday fasts, but little is known about brief periods of fasting (<24 hours). Reduced testosterone in low‐energy balance situations is hypothesized to reflect redirection of resources from reproduction to survival. This study tests the hypothesis that testosterone levels decrease during a minor caloric deficiency by assessing the effects of a single missed (evening) meal on morning testosterone in 23 healthy male participants, age 19–36. Methods: Participants provided daily saliva and urine samples for two baseline days and the morning following an evening fast (water only after 4 PM). Testosterone, cortisol, and luteinizing hormone were measured with enzyme immunoassays. Results: Fasting specimens had significantly lower overnight urinary luteinizing hormone (P = 0.045) and morning salivary testosterone than baseline (P = 0.037). In contrast to morning salivary testosterone, there was a significant increase in overnight urinary testosterone (P = 0.000) following the evening fast, suggesting an increase in urinary clearance rates. There was a marginal increase in overnight urinary cortisol (P = 0.100), but not morning salivary cortisol (P = 0.589). Conclusion: These results suggest the male reproductive axis may react more quickly to energetic imbalances than has been previously appreciated. Am. J. Hum. Biol., 2010. © 2010 Wiley‐Liss, Inc.