Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

Percutaneous transhepatic drainage is safe and effective in biliary obstruction – A single-center experience of 599 patients

Percutaneous transhepatic drainage is safe and effective in biliary obstruction – A single-center experience of 599 patient

Hierarchic finite level energy landscape model: To describe the refolding kinetics of phosphoglycerate kinase

One of the most intriguing predictions of energy landscape models is the existence of non-exponential protein folding kinetics caused by hierarchical structures in the landscapes. Here we provide the strongest evidence so far of such hierarchy and determine the time constants and weights of the kinetic components of the suggested hierarchic energy landscape. To our knowledge, the idea of hierarchical folding energy barriers has never been tested over such a broad timescale. Refolding of yeast phosphoglycerate kinase was initiated from the guanidine-unfolded state by stopped-flow or manual mixing and monitored by tryptophan fluorescence from 1 ms to 15 min. The strategy to build a model that describes folding of yeast phosphoglycerate kinase was to start from the simplest paradigm and modify it stepwise to the necessary minimal extent after repeated comparisons with the experiments. We made no a priori assumptions about the folding landscape. The result was a hierarchic finite level landscape model that quantitatively describes the refolding of yeast phosphoglycerate kinase from 1 ms to 15 min. The early steps of the folding process happen in the upper region of the landscape, where the surface has a hierarchic structure. This leads to stretched kinetics in the early phase of the folding. The lower region of the energy landscape is dominated by a trap that reflects the accumulation of molten globule intermediate state. From this intermediate, the protein can reach the global energy minimum corresponding to the native state through a cross-barrier folding step. 2006 by The American Society for Biochemistry and Molecular Biology, Inc

Orgasmic coitus triggered stillbirth via placental abruption: A case report

Sexual activity during healthy pregnancy is safe. There are little data on how coital activity affects outcome of the high-risk pregnancies. Hereby we report a case demonstrating that orgasmic coitus triggered placental abruption resulting in preterm stillbirth. A 38-year-old 8-para, 12-gravida woman lived unmarriedly with a constant partner in low socioeconomic conditions. Her previous pregnancies included 7 deliveries without complication, two early miscarriages and two pregnancy terminations. Her present pregnancy was complicated with gestational hypertension successfully treated with nifedipine. She had coitus 2 to 4 times a month, mostly without orgasm. The last coitus which happened in side-by-side position was accompanied by orgasm which continued in uterine hypertonicity and massive vaginal bleeding at 29 weeks gestation. Two hours subsequently, on admission to hospital, placental abruption and fetal demise were diagnosed. At the emergency cesarean section, a dead female infant weighing 1,510 g was born. Fetal pathology was not discovered. Placental histopathology showed retroplacental hematoma, intervillous and decidual hemorrhages, focal distal villous hypoplasia and avascular villuses. Patient’s recovery rapidly occurred after intensive care. Placental abruption complicates 0.4% - 1.0% of deliveries. It is known that most cases of abruption cannot be predicted and prevented. Our report suggests that orgasmic coitus may be a trigger for placental abruption in those women who have gestational hypertension and multiple risks for placental abruption. We infer from the above case that sexual intercourse is advised to avoid during pregnancy of such women in order to prevent placental abruption

Vascular supply of the metacarpophalangeal joint

To describe in detail the arterial vasculature of metacarpophalangeal joints 2-5 on cadaver specimens and to compare it to ultrasound imaging of healthy subjects.Eighteen hands of donated human cadavers were arterially injected and investigated with either corrosion casting or cryosectioning. Each layer of cryosectioned specimens was photographed in high-resolution. Images were then segmented for arterial vessels of the metacarpophalangeal (MCP) joints 2-5. The arterial pattern of the joints was reconstructed from the segmented images and from the corrosion cast specimens. Both hands of ten adult healthy volunteers were scanned focusing on the vasculature of the same joints with high-end ultrasound imaging, including color Doppler. Measurements were made on both cryosectioned arteries and Doppler images.The arterial supply of MCP joints 2-5 divides into a metacarpal and a phalangeal territory, respectively. The metacarpal half receives arteries from the palmar metacarpal arteries or proper palmar digital arteries, while the phalangeal half is supplied by both proper and common palmar digital arteries. Comparing anatomical and ultrasonographic results, we determined the exact anatomic location of normal vessels using Doppler images acquired of healthy joints. All, except three branches, were found with less than 50% frequency using ultrasound. Doppler signals were identified significantly more frequently in MCP joints 2-3 than on 4-5 (p< 0.0001). Similarly, Doppler signals differed in the number of detectable small, intraarticular vessels (p< 0.009), but not that of the large extraarticular ones (p< 0.1373). When comparing measurements acquired by ultrasound and on cadaver vessels, measurements using the former technique were found to be larger in all joints (p< 0.0001).Using morphological and ultrasonographic techniques, our study provides a high-resolution anatomical maps and an essential reference data set on the entire arterial vasculature of healthy human MCP 2-5 joints. We found that Doppler signal could be detected in less than 50% of the vessels of healthy volunteers except three locations. Intraarticular branches were detected with ultrasound imaging significantly more frequently on healthy MCP 2-3 joints, which should be taken into account when inflammatory and normal Doppler signals are evaluated. Our study also provides reference data for future, higher-resolution imaging techniques

Synthesis of ortho-Functionalized 4-Aminomethylpyridazines as Substrate-Like Semicarbazide-Sensitive Amine Oxidase Inhibitors

A series of 4-aminomethylpyridazines and -pyridazin-3(2H)-ones (“diaza-benzylamines”), bearing alkylamino side chains in ortho position relative to the CH2NH2 unit, was synthesized by catalytic hydrogenation of the corresponding nitriles in strongly acidic medium. N-Benzyl protecting groups either at the pyridazinone ring nitrogen or at an exocyclic nitrogen were selectively removed hydrogenolytically or by treatment with a Lewis acid. The new compounds were tested in vitro for semicarbazide-sensitive amine oxidase (SSAO) inhibitory activity and 4-(aminomethyl)-N,N-diethylpyridazine-3,5-diamine (22) was found to be the most active representative

Structural Characterization of Arginine Fingers: Identification of an Arginine Finger for the Pyrophosphatase dUTPases

Arginine finger is a highly conserved and essential residue in many GTPase and AAA+ ATPase enzymes that completes the active site from a distinct protomer, forming contacts with the γ-phosphate of the nucleotide. To date, no pyrophosphatase has been identified that employs an arginine finger fulfilling all of the above properties; all essential arginine fingers are used to catalyze the cleavage of the γ-phosphate. Here, we identify and unveil the role of a conserved arginine residue in trimeric dUTPases that meets all the criteria established for arginine fingers. We found that the conserved arginine adjacent to the P-loop-like motif enables structural organization of the active site for efficient catalysis via its nucleotide coordination, while its direct electrostatic role in transition state stabilization is secondary. An exhaustive structure-based comparison of analogous, conserved arginines from nucleotide hydrolases and transferases revealed a consensus amino acid location and orientation for contacting the γ-phosphate of the substrate nucleotide. Despite the structurally equivalent position, functional differences between arginine fingers of dUTPases and NTPases are explained on the basis of the unique chemistry performed by the pyrophosphatase dUTPases

Quantitative Analysis of Inflammatory Uterine Lesions of Pregnant Gilts with Digital Image Analysis Following Experimental PRRSV-1 Infection

Reproductive disorders caused by porcine reproductive and respiratory syndrome virus-1 are not yet fully characterized. We report QuPath-based digital image analysis to count inflammatory cells in 141 routinely, and 35 CD163 immunohistochemically stained endometrial slides of vaccinated or unvaccinated pregnant gilts inoculated with a high or low virulent PRRSV-1 strain. To illustrate the superior statistical feasibility of the numerical data determined by digital cell counting, we defined the association between the number of these cells and endometrial, placental, and fetal features. There was strong concordance between the two manual scorers. Distributions of total cell counts and endometrial and placental qPCR results differed significantly between examiner1\u27s endometritis grades. Total counts\u27 distribution differed significantly between groups, except for the two unvaccinated. Higher vasculitis scores were associated with higher endometritis scores, and higher total cell counts were expected with high vasculitis/endometritis scores. Cell number thresholds of endometritis grades were determined. A significant correlation between fetal weights and total counts was shown in unvaccinated groups, and a significant positive correlation was found between these counts and endometrial qPCR results. We revealed significant negative correlations between CD163+ counts and qPCR results of the unvaccinated group infected with the highly virulent strain. Digital image analysis was efficiently applied to assess endometrial inflammation objectively