Functional Redundancy of SWI/SNF Catalytic Subunits in Maintaining Vascular Endothelial Cells in the Adult Heart

Rationale: Mating type switching/sucrose non-fermenting (SWI/SNF) chromatin-remodeling complexes utilize either BRG1 or BRM as a catalytic subunit to alter nucleosome position and regulate gene expression. BRG1 is required for vascular endothelial cell (VEC) development and embryonic survival, whereas BRM is dispensable. Objective: To circumvent embryonic lethality and study Brg1 function in adult tissues, we used conditional gene targeting. To evaluate possible Brg1-Brm redundancy, we analyzed Brg1 mutant mice on wild-type and Brm-deficient backgrounds. Methods and Results: The inducible Mx1-Cre driver was used to mutate Brg1 in adult mice. These conditional-null mutants exhibited a tissue-specific phenotype and unanticipated functional compensation between Brg1 and Brm. Brg1 single mutants were healthy and had a normal lifespan, whereas Brg1/Brm double mutants exhibited cardiovascular defects and died within 1 month. BRG1 and BRM were required for the viability of VECs but not other cell types where both genes were also knocked out. The VEC phenotype was most evident in the heart, particularly in the microvasculature of the outer myocardium, and was recapitulated in primary cells ex vivo. VEC death resulted in vascular leakage, cardiac hemorrhage, secondary death of cardiomyocytes due to ischemia, and ventricular dissections. Conclusions: BRG1-catalyzed SWI/SNF complexes are particularly important in cardiovascular tissues. However, in contrast to embryonic development, in which Brm does not compensate, Brg1 is required in adult VECs only when Brm is also mutated. These results demonstrate for the first time that Brm functionally compensates for Brg1 in vivo and that there are significant changes in the relative importance of BRG1- and BRM-catalyzed SWI/SNF complexes during the development of an essential cell lineage.     

PGRP-LB is a maternally transmitted immune milk protein that influences symbiosis and parasitism in tsetse's offspring

Beneficial microbe functions range from host dietary supplementation to development and maintenance of host immune system. In mammals, newborn progeny are quickly colonized with a symbiotic fauna that is provisioned in mother's milk and that closely resembles that of the parent. Tsetse fly (Diptera: Glossinidae) also depends on the obligate symbiont Wigglesworthia for nutritional supplementation, optimal fecundity, and immune system development. Tsetse progeny develop one at a time in an intrauterine environment and receive nourishment and symbionts in mother's milk. We show that the host Peptidoglycan Recognition Protein (PGRP-LB) is expressed only in adults and is a major component of the milk that nourishes the developing progeny. The amidase activity associated with PGRP-LB may scavenge the symbiotic peptidoglycan and prevent the induction of tsetse's Immune Deficiency pathway that otherwise can damage the symbionts. Reduction of PGRP-LB experimentally diminishes female fecundity and damages Wigglesworthia in the milk through induction of antimicrobial peptides, including Attacin. Larvae that receive less maternal PGRP-LB give rise to adults with fewer Wigglesworthia and hyperimmune responses. Such adults also suffer dysregulated immunity, as indicated by the presence of higher trypanosome densities in parasitized adults. We show that recPGRP-LB has antimicrobial and antitrypanosomal activities that may regulate symbiosis and impact immunity. Thus, PGRP-LB plays a pivotal role in tsetse's fitness by protecting symbiosis against host-inflicted damage during development and by controlling parasite infections in adults that can otherwise reduce host fecundity.     

Clinical and magnetic resonance imaging findings of the temporomandibular joint and masticatory muscles in patients with rheumatoid arthritis

The aim of this study was to investigate the clinical, radiographic, and magnetic resonance imaging (MRI) findings of temporomandibular joint (TMJ) and masticatory muscles in rheumatoid arthritis (RA) patients. Twenty-eight RA patients and 29 healthy subjects were participated in the study. The patient underwent clinical and laboratory investigation. DAS28 scores were calculated. Lateral panoramic radiography was performed to evaluate condylar erosion and condylar movement. Craniofacial MRI was performed to evaluate TMJ and masseter, medial and lateral pterygoid muscles’ thickness, and cross-sectional area. It was found that the mean maximal interincisal distance, range of lateral, retrusive (P < 0.05) and protrusive motion were all lesser in RA group. Lateral panoramic radiography revealed a distinct erosion in 10.7% (3/28) and restricted condylar movement in 53.6% (15/28) of RA patients. Two RA patients demonstrating marked condylar erosion in lateral panoramic radiographs were RF negative and had DAS28 scores 3.41 and 4.61. MRI findings revealed condylar erosion and effusion in one RA patient and atrophic changes of masticatory muscles in another patient. There was no statistical significance between RA and healthy groups for the thickness and cross-sectional areas of the masticatory muscles. RA group revealed a strong linear relationship for the right and left muscle thickness and cross-sectional areas in regression analysis. TMJ symptoms are frequent findings and thought to be affected from mean disease duration in RA. Laboratory findings should be considered for disease activity–related TMJ involvement. RA patients did not present muscular atrophy or hypertrophy.     

The effects of ghrelin on colonic anastomosis healing in rats

OBJECTIVES:

In addition to its roles in the stimulation of growth hormone secretion and the regulation of appetite and metabolism, ghrelin exerts immunomodulatory, anti-inflammatory and antioxidant actions in several organ systems. In this study, we investigated the effects of ghrelin on the healing of experimental colonic anastomoses.

METHODS:

Wistar rats were randomly divided into two groups (n = 10 in each). A segment of colon was excised, and an end-to-end anastomosis was performed in the distal colon. The Ghrelin Group received 10 ng/kg/day IP ghrelin for seven days postoperatively, whereas the Control Group received an identical volume of saline. On the seventh postoperative day, the anastomotic bursting pressures and hydroxyproline levels were measured, and adhesion formation around the anastomoses was examined. Histopathological analyses were performed to evaluate inflammatory cell infiltration, fibroblast infiltration, collagen density and neovascularization.

RESULTS:

In the Ghrelin Group, the bursting pressure and hydroxyproline levels were significantly higher than in the Control Group. The adhesion formation scores were lower in the Ghrelin Group than in the Control Group. Although the inflammatory cell infiltration was diminished in the Ghrelin Group, the degrees of fibroblast infiltration, collagen density and neovascularization were not significantly different between the groups.

CONCLUSION:

Our results indicate that ghrelin improves the healing of colonic anastomoses in rats.     

The Effect of Removable Partial Dentures on Alveolar Bone Resorption: A Retrospective Study with Cone‐Beam Computed Tomography

Purpose: The aim of this study was to compare vertical and horizontal mandibular alveolar bone resorption by measuring bone morphological variation in Kennedy Class II removable partial denture (RPD) wearers and non‐wearers using cone‐beam computed tomography (CBCT). Materials and Methods: In total, 124 sites in the CBCT scans of 62 (29 RPD non‐wearers, 33 RPD wearers) Kennedy Class II patients were analyzed retrospectively. Three‐dimensional representations of the mandible with superimposed cross‐sectional slices were developed with the CBCT scans to evaluate the mandibular alveolar height and width by measuring distances between the mandibular canal, mylohyoid ridge, alveolar crest, and lower border of the mandible in four regions (eight sites) of Kennedy Class II non‐wearers and wearers of RPDs. Results: Mandibular alveolar bone height and width were significantly lower in edentulous sites when compared with dentate sites in both Kennedy Class II non‐wearers and wearers of RPDs (p < 0.05). Additionally, mean vertical and horizontal mandibular bone resorption was significantly higher in RPD wearers than in non‐wearers (p < 0.05). Conclusions: Vertical and horizontal alveolar bone resorption was found to be higher in the RPD wearing patients when comparing the dentate and edentulous sites.     

An electrophysiologic evaluation of whether open and laparoscopic techniques used in pediatric inguinal hernia repairs affect the genitofemoral nerve

Background

A prospective study was performed to evaluate the effect of inguinal hernia repairs on the genitofemoral nerve (GFN), and to compare postoperative electrophysiologic changes in the GFN of patients who had undergone either open or laparoscopic surgery.

Methods

Seventy patients with a mean age of 6.48 ± 3.49 were enrolled in the study. Either open or laparoscopic techniques were used to operate on the patients' inguinal hernias. In all cases, bilateral GFN motor responses were investigated electrophysiologically using surface electrodes on three occasions: preoperatively, in the first month, and third month postoperatively. t-Tests were used to compare changes in the GFN.

Results

Preoperative mean latency of the GFN in all groups was found to be significantly prolonged on the hernia side, compared with the non-hernia side (P = 0.01). Although no difference was observed in the latency levels of the GFN on the operated side at the preoperative and early postoperative stages, GFN latency levels decreased significantly in the late postoperative period in the laparoscopic group (P < 0.05). In the late postoperative period, amplitudes of GFN motor responses were significantly higher in the laparoscopic group than the open repair group (0.91 ± 0.11 mV and 0.57 ± 0.053 mV, respectively; P < 0.05).

Conclusion

Preoperative prolonged latency of GFN on the hernia side is likely to occur due to the pressure on the nerve caused by the hernia mass. By surgically removing the hernia mass, this buildup of pressure is prevented, decreasing the latency of the GFN. The significantly higher motor response amplitudes and decreased latency in the late postoperative stage for the laparoscopic group may be due to the fact that this technique is less invasive.     

Use of home sphygmomanometers in Turkey: a nation-wide survey

The purposes of this study were to detect the prevalence of ownership of a home sphygmomanometer among hypertensive subjects through a nation-wide survey, to investigate parameters affecting ownership of a sphygmomanometer, to compare how home blood pressure monitoring (HBPM) was actually used in daily practice with some aspects of the current guidelines, and to discuss what we implemented to increase the reliability of HBPM in a developing country. A total of 2747 hypertensive patients from 34 cities, representative of the Turkish population, were enrolled in the study. A multiple-choice questionnaire was administered to each participant using the computer-assisted telephone interviewing method. Among 2747 hypertensive patients, 1281 of them (46.6%) had a home sphygmomanometer. Most of the patients were using wrist devices. The factors associated with ownership of a sphygmomanometer were female gender, older age, obesity, higher educational status, higher income level, living in urban areas, awareness of hypertension and anti-hypertensive drug usage. Only 16% of the devices were used on the advice of a physician. The patients learned usage of their device mainly from the sellers and their relatives. The ownership of a home sphygmomanometer is common among hypertensive patients in Turkey, but regular monitoring of blood pressure before physician visits is rare despite common ownership of these devices. Daily practice of HBPM in Turkey was far from the recommendations of the current guidelines. More effort is needed to improve the reliability of HBPM.     

Doubling the clopidogrel dose in patients with reduced responsiveness to the standard dose is associated with a limited effectiveness as evaluated by impedance aggregometry

BackgroundDifferent methods are available for quantifying platelet function inhibition. Measuring vasodilator-stimulated phosphoprotein (VASP) phosphorylation is currently the most specific method for assessing the clopidogrel effect. The aim of our study was to compare different tests in view of a clinically applicable bedside test. Further, we examined whether doubling the clopidogrel dose to 150 mg/d in clopidogrel low-responder would lead to a reduction in platelet reactivity.Methods and resultsADP-, ADP Hs-, and TRAP-induced platelet aggregation were measured by impedance aggregometry in 100 patients with CAD and 18 healthy controls. Moreover, platelet aggregation was assessed by flow cytometrical detection of VASP-phosphorylation and surface P-selectin in a subgroup of 34 patients and in healthy controls. Another 10 patients with CAD, identified as low-responder, were treated with a clopidogrel dose of 150 mg/d. Thereafter, ADP-induced platelet aggregation was assessed by impedance aggregometry. Significant correlations were observed between ADP-induced platelet aggregation assessed by VASP-phosphorylation and by impedance aggregometry. Doubling the dose of clopidogrel to 150 mg/d was associated with a reduction of ADP-induced platelet aggregation in only 60% of the patients.ConclusionsImpedance aggregometry is a valuable bedside test to assess platelet function inhibition. Doubling the clopidogrel dose is not effective to reduce high on-treatment platelet reactivity in almost half of these patients, pointing to the need of a more powerful platelet inhibitor.