Anatomical Compliance of Cavopulmonary Assist Device Designs: A Virtual Fitting Study in Fontan Patients.

Several device designs for cavopulmonary mechanical circulatory support (MCS) are under investigation, however, challenged by the Fontan population's heterogeneity in size, cardiovascular and thoracic anatomy. This study aimed to preclinically assess the anatomical compliance of proposed device designs in silico. Representative double- and single-outlet cavopulmonary assist device (CPAD) designs were virtually implanted into CT imaging data of 10 patients previously palliated with total cavopulmonary connection (TCPC) for functionally univentricular hearts.

Identification of CX3CR1 mononuclear phagocyte subsets involved in HIV-1 and SIV colorectal transmission.

The difficulty to unambiguously identify the various subsets of mononuclear phagocytes (MNPs) of the intestinal has hindered our understanding of the initial events occurring after mucosal exposure to HIV-1. Here, we compared the composition and function of MNP subsets at steady-state and following and viral exposure in human and macaque colorectal tissues. Combined evaluation of CD11c, CD64, CD103, and CX3CR1 expression allowed to differentiate MNPs subsets common to both species.

Serum amyloid P component is an essential element of resistance against Aspergillus fumigatus.

Serum amyloid P component (SAP, also known as Pentraxin 2; APCS gene) is a component of the humoral arm of innate immunity involved in resistance to bacterial infection and regulation of tissue remodeling. Here we investigate the role of SAP in antifungal resistance. Apcs mice show enhanced susceptibility to A.

Nanoscale Study of Calcium Handling Remodeling in Right Ventricular Cardiomyocytes Following Pulmonary Hypertension.

Pulmonary hypertension is a complex disorder characterized by pulmonary vascular remodeling and right ventricular hypertrophy, leading to right heart failure. The mechanisms underlying this process are not well understood. We hypothesize that the structural remodeling occurring in the cardiomyocytes of the right ventricle affects the cytosolic Ca handling leading to arrhythmias.

Nanobodies as Versatile Tool for Multiscale Imaging Modalities.

Molecular imaging is constantly growing in different areas of preclinical biomedical research. Several imaging methods have been developed and are continuously updated for both in vivo and in vitro applications, in order to increase the information about the structure, localization and function of molecules involved in physiology and disease. Along with these progresses, there is a continuous need for improving labeling strategies.

Author Correction: Evaluation of cell metabolic adaptation in wound and tumour by Fluorescence Lifetime Imaging Microscopy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Evaluation of cell metabolic adaptation in wound and tumour by Fluorescence Lifetime Imaging Microscopy.

Acidic pH occurs in acute wounds progressing to healing as consequence of a cell metabolic adaptation in response to injury-induced tissue hypoperfusion. In tumours, high metabolic rate leads to acidosis affecting cancer progression. Acidic pH affects activities of remodelling cells in vitro.

Circ_Lrp6, a Circular RNA Enriched in Vascular Smooth Muscle Cells, Acts as a Sponge Regulating miRNA-145 Function.

Rationale: microRNAs (miRNAs) modulate gene expression by repressing translation of targeted genes. Previous work has established a role for miRNAs in regulating vascular smooth muscle cell (VSMC) activity. Whether circular RNAs are involved in the modulation of miRNA activity in VSMCs is unknown.

Growth differentiation factor 15 as a radiation-induced marker in oral carcinoma increasing radiation resistance.

Background: Growth differentiation factor 15 (GDF15) is involved in tumor pathogenesis of oral squamous cell carcinoma (OSCC). The aim of this study was an investigation of the potential influence of GDF15 on radioresistance of OSCC cells in vitro.

Methods: Oral squamous cell carcinoma cell lines were irradiated with 0, 2, or 6 Gy, and GDF15 expression in the supernatant per survived cell colony was examined with ELISA.

Homolog of allograft inflammatory factor-1 induces macrophage migration during innate immune response in leech.

Allograft inflammatory factor-1 (AIF-1) is a 17-kDa cytokine-inducible calcium-binding protein that, in vertebrates, plays an important role in the allograft immune response. Its expression is mostly limited to the monocyte/macrophage lineage. Until recently, AIF-1 was assumed to be a novel molecule involved in inflammatory responses.

In vitro and in vivo evaluation of dihydropyrimidinone C-5 amides as potent and selective alpha(1A) receptor antagonists for the treatment of benign prostatic hyperplasia.

alpha(1) Adrenergic receptors mediate both vascular and lower urinary tract tone, and alpha(1) receptor antagonists such as terazosin (1b) are used to treat both hypertension and benign prostatic hyperplasia (BPH). Recently, three different subtypes of this receptor have been identified, with the alpha(1A) receptor being most prevalent in lower urinary tract tissue. This paper explores 4-aryldihydropyrimidinones attached to an aminopropyl-4-arylpiperidine via a C-5 amide as selective alpha(1A) receptor subtype antagonists.

Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 2. Approaches to eliminate opioid agonist metabolites via modification of linker and 4-methoxycarbonyl-4-phenylpiperidine moiety.

We have previously described compound 1a as a high-affinity subtype selective alpha(1a) antagonist. In vitro and in vivo evaluation of compound 1a showed its major metabolite to be a mu-opioid agonist, 4-methoxycarbonyl-4-phenylpiperidine (3). Several dihydropyrimidinone analogues were synthesized with the goal of either minimizing the formation of 3 by modification of the linker or finding alternative piperidine moieties which when cleaved as a consequence of metabolism would not give rise to mu-opioid activity.

Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 1. Structure-activity relationship in dihydropyrimidinones.

Dihydropyrimidinones such as compound 12 exhibited high binding affinity and subtype selectivity for the cloned human alpha(1a) receptor. Systematic modifications of 12 led to identification of highly potent and subtype-selective compounds such as (+)-30 and (+)-103, with high binding affinity (K(i) = 0.2 nM) for alpha(1a) receptor and greater than 1500-fold selectivity over alpha(1b) and alpha(1d) adrenoceptors.

[The duodenojejunal flexure--a gap in the routine diagnosis of gastrointestinal bleeding].

History And Admission Findings: Because of tarry stools a 64-year-old woman had two years previously undergone oesophagogastroduodenoscopy (OGD), coloscopy and examination of the small intestine (according to Sellink) without significant findings. She was again hospitalized because of anemia (6.1 g/dl).

Design and synthesis of N-alkylated saccharins as selective alpha-1a adrenergic receptor antagonists.

Benign prostatic hyperplasia can be managed pharmacologically with alpha-1 adrenergic receptor antagonists. Agents that demonstrate selectivity for the alpha-1a receptor subtype may offer advantages in clinical applications with respect to hypotensive side effects. The N-alkylated saccharins reported here represent a new class of subtype selective alpha-1a adrenergic receptor antagonists which demonstrate potent effects on prostate function in vivo and are devoid of blood pressure side effects.

Rupture of therapeutic oleothorax leading to paraffin oil aspiration and dissemination of tuberculosis--a fatal late complication of tuberculosis therapy in the 1940s.

In the 1940s, oleothorax (paraffin oil instillation) was widely used to treat patients with apical tuberculosis. The oil plombage should have been removed after a few years; however, since oleothoraces were usually asymptomatic, removal was uncommon. These in the meantime elderly patients are at risk of late complications, such as rupture of the oleothorax and aspiration of oil.

Design and synthesis of novel alpha1a adrenoceptor-selective dihydropyridine antagonists for the treatment of benign prostatic hyperplasia.

We report the synthesis and evaluation of novel alpha1a adrenoceptor subtype-selective antagonists. Systematic modification of the lipophilic 4,4-diphenylpiperidinyl moiety of the dihydropyridine derivatives 1 and 2 provided several highly selective and potent alpha1a antagonists. From this series, we identified the 4-(methoxycarbonyl)-4-phenylpiperidine analogue SNAP 5540 (-) [(-)-63] for further characterization.

In vivo pharmacology of L-159,913, a new highly potent and selective nonpeptide angiotensin II receptor antagonist.

The present study was designed to characterize the in vivo pharmacology of L-159,913 (4-[[2'-(N-benzoylsulfamoyl)biphenyl-4-yl]-5butyl-2,4-dihydr o-2- [2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one); a potent All receptor antagonist. In normotensive rats, dogs, rhesus monkeys, and chimpanzees, L-159,913 inhibited All-induced elevations in blood pressure. In conscious rats, the relative potencies (ED50) were 0.

Discovery of L-162,313: a nonpeptide that mimics the biological actions of angiotensin II.

L-162,313 (5,7-dimethyl-2-ethyl-3-[[4-[2(n- butyloxycarbonylsulfonamido)-5-isobutyl-3-thienyl]phenyl]methyl]- imadazo[4,5-b]pyridine) is a nonpeptide that mimics the biological actions of angiotensin II (ANG II). The intravenous administration of L-162,313 increased blood pressure in the rat. The maximum increase in mean arterial pressure (MAP) was not different from the maximum response to ANG II in the same preparation.

In vivo pharmacology of a novel AT1 selective angiotensin II receptor antagonist, MK-996.

MK-996, N-(4'-(5,7-dimethyl-2-ethyl-3H-imidazo[4,5-b]pyridin-3-yl- methyl)1,1'-biphenyl-2-yl)-sulfonylbenzamide, is a potent, orally active, highly selective, nonpeptide angiotensin II (AII) receptor antagonist. MK-996 prevents the pressor response to intravenous AII in the conscious rat, dog, and rhesus monkey (ED50, mg/kg; oral/intravenous = 0.067/0.

Biotransformation of 5-chloro-3-phenylthioindole-2-carboxamide (L-734,005) in rhesus monkeys and rat liver microsomes to a potent HIV-1 reverse transcriptase inhibitor.

Rhesus monkeys were dosed orally with 10 mg/kg 5-chloro-3-phenylthioindole-2-carboxamide (L-734,005), a nonnucleoside human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitor, in polyethylene glycol 300. Plasma samples from these monkeys demonstrated greater bioactivity in an HIV-1 reverse transcriptase inhibition assay than anticipated from the parent compound concentrations as determined by an HPLC-UV assay. One major and three minor metabolites, as well as the parent compound, were detected in the plasma.

A rapid bioassay for the determination of non-nucleoside HIV-1 reverse transcriptase inhibitor plasma levels.

A rapid method for measuring pyridinone HIV-1 reverse transcriptase inhibitor plasma levels was necessary for identifying potential clinical candidates and for choosing a clinical formulation. Due to its sensitivity to the pyridinones, ability to tolerate extraneous material, and its capability for rapid, high through-put screening, the HIV-1 RT assay was developed into a bioassay for determining plasma levels of the pyridinones in Rhesus monkey plasma. With this assay, dose proportionality of L-697, 639 was established.