bluuebunny/crossref_metadata_2025 huggingface dataset:
Concept and Computational Design for a Bioartificial Nephron-On-A-Chip
Authors: Weinberg E. , Kaazempur-Mofrad M. , Borenstein J.
Published: January 2018

A MEMS-based, (Micro Electro Mechanical System) bioartificial device is proposed for replicating the function of a single nephron. Consistent with the anatomy and physiology of humans, our device has 3 distinct sections, replicating the function of the glomerulus, the proximal tubule, and the loop of Henle. Construction of a bioartificial loop of Henle in particular requires control of diffusion-scale features. The proposed device can be built using existing microfabrication technologies and populated with various renal cell types. A computational model is also developed to analyze the coupled, multiphase mass transport in this system. Using the model, a design is generated with flow and solute transport properties matching those of the human nephron
The Alpha-Like Surface Proteins: An Example of an Expanding Family of Adhesins
Authors: Creti R. , Baldassarri L. , Montanaro L. , Arciola C.R.
Published: January 2018

The Alpha-like protein (Alp) family, repeat-containing surface proteins once thought to be important adhesion factors confined to pathogenic streptococci and enterococci, is broader than previously known. Analysis of the annotated microbial genomes has identified new potential members of the Alp family not only in other Gram- positive opportunistic pathogens but also in commensal microflora of the human gut and the skin. This finding has highlighted the importance of genome sequencing projects for unraveling in greater detail lateral gene transfer events involving virulence factors between pathogens and commensals. These should receive constant attention not only as part of infectious disease prevention programs, but also in the food and biotechnology industries. (Int J Artif Organs 2008; 31: 834–40)
The Selection of Appropriate Bacterial Strains in Preclinical Evaluation of Infection-Resistant Biomaterials
Authors: Campoccia D. , Montanaro L. , Moriarty T.F. , Richards R.G. , Ravaioli S. , Arciola CR.
Published: January 2018

Implant-related infections are broadly recognized as one of the most serious and devastating complications associated with the use of biomaterials in medical practice. The growing interest and need for the development of implant materials with reduced susceptibility to microbial colonization and biofilm formation has necessitated the development of a series of in vitro and in vivo models for evaluation and preclinical testing. Current technologies provide these investigations with an ample choice of qualitative and quantitative techniques for an accurate assessment of the bioactivity and anti-infective efficacy of any new compound or device. These tests are typically performed using a reference bacterial strain designated as the test or reference strain. Recent molecular epidemiological studies have identified the complex clonal nature of most prevalent etiological agents implicated in implant-associated infections. New information which is continually emerging on the identity and the characteristics of both sporadic and epidemic clones must be considered when selecting a reference. A new emerging requirement is that the strain should be representative of the clones causing clinically relevant infections; they should, therefore, belong to the most prevalent epidemic clones rather than to sporadic ones, which may occur in only 1 out of 200 infections or even fewer. The correct choice of reference strain for preclinical tests is of crucial importance for the clinical significance of the achieved results. In this paper we report our experience and recommendations regarding this issue. (Int J Artif Organs 2008; 31: 841–7)
Photodynamic Action of Merocyanine 540 on Staphylococcus Epidermidis Biofilms
Authors: Sbarra M. S. , Di Poto A. , Arciola C. R. , Saino E. , Sharma M. , Bragheri F. , Cristiani I. , Speziale P. , Visai L.
Published: January 2018

Photodynamic treatment (PDT) has been proposed as a new approach for inactivation of biofilms associated with medical devices that are resistant to chemical additives or biocides. In this study, we evaluated the antimicrobial activity of merocyanine 540 (MC 540), a photosensitizing dye that is used for purging malignant cells from autologous bone marrow grafts, against Staphylococcus epidermidis biofilms. Effect of the combined photodynamic action of MC 540 and 532 nm laser was investigated on the viability and structure of biofilms of two Staphylococcus epidermidis strains, RP62A and 1457. Significant inactivation of cells was observed when biofilms were exposed to MC 540 and laser simultaneously. The effect was found to be light dose-dependent but S. epidermidis 1457 biofilm proved to be slightly more susceptible than S. epidermidis RP62A biofilm. Furthermore, significant killing of both types of cells was attained even when a fixed light dose was delivered to the biofilms. Confocal laser scanning microscope (CLSM) analysis indicated damage to bacterial cell membranes in photodynamically treated biofilms, while disruption of PDT-treated biofilm was confirmed by scanning electron microscopy (SEM). (Int J Artif Organs 2008; 31: 848–57)
Impact of Hemodialysis Therapy on Hepatitis C Virus Infection: A Deeper Insight
Authors: Fabrizi F. , Messa P. , Martin P.
Published: January 2018

Hepatitis C Virus (HCV) infection remains prevalent in patients receiving regular dialysis all over the world. The adverse impact of anti-HCV serologic status on mortality in the dialysis population has been documented. Antiviral therapy for hepatitis C in chronic kidney disease (CKD) patients, including the dialysis population, is still unsatisfactory. Several findings support a different course of HCV in dialysis patients versus the non-uremic population. The HCV viral load appears lower in hemodialysis patients with HCV despite the immune compromise caused by chronic uremia; the histologic abnormalities seem milder, and a severe clinical course of chronic hepatitis C is unusual in most hemodialysis (HD) patients. It appears that the HD procedure per se can preserve patients from an aggressive course of HCV by reducing the viral load (HCV RNA). The mechanisms by which the HD procedure lowers HCV viremia remain largely speculative: the passage of viral particles into the dialysate, the trapping of the virus on the surface of the dialyzer membrane, and an indirect host-mediated mechanism have been cited. The latter hypothesis implicates the production of interferon-α, hepatocyte growth factor, or other cytokines provided with antiviral activities during the hemodialysis sessions. Clinical trials aimed at clarifying this issue are under way.
Thrice-Weekly In-Center Nocturnal Hemodialysis: An Effective Strategy to Optimize Chronic Dialysis Therapy
Authors: Cravedi P. , Ruggenenti P. , Mingardi G. , Sghirlanzoni M.C. , Remuzzi G.
Published: January 2018

Objectives

Daily nocturnal hemodialysis (NHD) has been proposed as a valuable strategy to improve outcomes for patients on conventional hemodialysis (CHD), but it is burdened by high costs and logistic issues. Thrice NHD might represent a more affordable approach to improve hemodialysis patient outcome.

Methods

Here we retrospectively analyzed the data on blood pressure, body weight, and hematochemical parameters in a cohort of 7 patients (mean age 50.4 ± 11.0 years, duration of CHD 14.3 ± 11.5 years) who registered in the NHD program at the dialysis unit of Ospedali Riuniti, Bergamo, Italy. Data for the 2 first years of NHD were compared with those of the last year on CHD.

Results

At 2 years after start of NHD, we found a significant decrease in systolic (149.4 ± 16.6 vs. 128.4 ± 26.0 mm Hg, p<0.001) and diastolic (87.7 ± 11.1 vs. 79.6 ± 16.7 mm Hg, p<0.05) blood pressure, along with a significant reduction in the use of per-patient antihypertensive agents (1.17 ± 1.19 vs. 0.47 ± 0.89, p<0.05) and an increase in dry body weight (61.4 ± 21.8 vs. 67.1 ± 16.4 kg, p<0.001). Moreover, patients had a significant reduction in phosphate levels (6.2 ± 2.4 vs. 5.4 ± 3.0 mg/dL, p<0.01). The procedure was safe and well tolerated and did not require extra cost for ad hoc facilities.

Conclusion

NHD is an effective approach to optimize chronic dialysis therapy.
Subjective Satisfaction and Quality of Life in Patients Prior to Listing for Liver Transplantation
Authors: Minazzato L. , Amodio P. , Cillo U. , Zanus G. , Schiff S. , Bombonato G. , Salari A. , Bianco T.
Published: January 2018

Objectives

Differences in health-related quality of life (HR-QoL) perception between alcohol-abusing and non-substance-dependent subjects with liver cirrhosis could depend on differences in personality profile and influence management of patients awaiting liver transplant.

Methods

We compared the perceptions of disease state in 78 male patients of similar disease severity divided into 2 groups based on etiology of cirrhosis: 47% had alcoholic cirrhosis, and 53% had hepatitis C virus (HCV)-related cirrhosis without alcohol abuse. Patients’ perception of disease state was determined using the SAT-P questionnaire (a self-administered questionnaire that provides a global assessment of perceived HR-QoL and subjective well-being). The assessment yields 2 scales: an analytic scale based on 32 variables and a synthetic scale based on 5 factors.

Results

In patients with alcohol-related disease, “psychological function” was found to be more impaired, while “sleep, diet, and free time” was less impaired compared with subjects with HCV-related cirrhosis, suggesting dysfunction related to substance abuse with personality disturbance.

Conclusions

The perception of disease state is different in alcohol-abusing patients with cirrhosis compared with those with cirrhosis unrelated to alcohol.
Evaluation of Vascular Calcifications in CKD Patients
Authors: Adragão Teresa
Published: January 2018

In observational studies on dialysis patients, there has been a consistent association between vascular calcifications and mortality. Hyperphosphatemia and calcium treatment are some of the factors associated with development of vascular calcifications, especially in the presence of low bone turnover disease. Several non-invasive imaging techniques have been used to screen for the presence of vascular calcifications: plain X-Ray, echocardiography, ultrasonography, and computed tomography. Presence of vascular calcifications is a warning sign for increased cardiovascular risk and this information may be relevant for choosing the most suitable treatment for dialysis patients.
The Control of Hyperphosphatemia in Chronic Kidney Disease: Which Phosphate Binder?
Authors: Ketteler Markus
Published: January 2018

Hyperphosphatemia is currently regarded as a key mortality risk predictor in late CKD stages and especially in patients on dialysis. Fortunately, the armatorium to effectively treat hyperphosphatemia in end-stage renal disease has grown in recent years, and we gained an improved understanding of potential benefits and harms of specific compounds. Most interestingly, novel insights into the pathophysiology of calcium and phosphate handling, especially, the discovery of the phosphatonin FGF23, suggest a more complex assessment of phosphate balance especially in predialysis stages is warranted. This assessment should probably include measurements of fractional phosphate excretion and phosphatonin levels to objectively judge and effectively correct phosphate overload, however, clinical data on calcium and phosphate metabolism in CKD stages 3 – 4 are still scarce. This overview will both discuss aspects of pathophysiology of phosphate regulation and current and future clinical treatement approaches.
Calcimimetics in the Chronic Kidney Disease-Mineral and Bone Disorder
Authors: Bover Jordi , Aguilar Armando , Baas Juan P. , Reyes Joselyne , Lloret Maria -J. , Farré Neus , Olaya Mayte , Canal Cristina , Marco Helena , Andrés Enric , Trinidad Pedro , Ballarín José
Published: January 2018

Mineral and bone disorders (MBD) are both an early and very common complication of chronic kidney disease (CKD). It is now accepted that they represent a significant risk factor, explaining the high cardiovascular morbidity and mortality in CKD patients. During the last decade, we have been witnessing many advances in the nomenclature, classification, pathophysiology, diagnosis, and treatment of CKD and some of its complications, such as CKD-MBD. The identification of the calcium-sensing receptor (CaSR) involvement in the pathogenesis of primary and secondary hyperparathyroidism (SHPT) and the availability of a new class of drugs called calcimimetics are two outstanding examples. Cinacalcet, the only available calcimimetic, has been shown to be a very effective therapeutic tool in CKD-MBD. Many clinical trials with cinacalcet in hemodialysis patients with SHPT have shown a reduction in parathyroid hormone, calcium (Ca), phosphate (P) and Ca x P product levels, allowing far greater success in reaching therapeutic goals as recommended by international guidelines. Additionally, some studies have shown that the use of cinacalcet may improve other aspects of CKD-MBD, reducing the risk of vascular calcification and parathyroidectomy, among others. Prospective studies on dialysis patients, with hard endpoint data, are currently underway. This review summarizes the most significant aspects of calcimimimetics based on both experimental and clinical results, underlining their possibilities not only for the treatment of isolated SHPT but also for other CKD-MBD related conditions.
Application of Wavelet Analysis to the Phonocardiographic Signal of Mechanical Heart Valve Closing Sounds
Authors: Bagno Andrea , Anzil Federico , Tarzia Vincenzo , Pengo Vittorio , Ruggeri Alfredo , Gerosa Gino
Published: January 2018

Heart valve disorders, caused by congenital defects, rheumatic fever, calcification, myocardial infarction and other cardiovascular diseases, often require native valves to be replaced by bio-prosthetic devices or mechanical heart valves (MHVs). Among MHVs, bileaflet valves are usually preferred for their hemodynamic features, similar to physiological ones, and their durability, but they are prone to complications due to thromboembolic events. Due to the asynchronous closure of the leaflets, bileaflet MHVs are also known to produce closing sounds typically characterized by the presence of two peaks in the time domain. The detection of this “double click” in the signal may be useful for the early diagnosis of bileaflet MHV malfunction. The closing sound is actually a non-stationary signal that can be properly explored by means of time-frequency analysis.

This paper describes a preliminary approach to the investigation of bileaflet MHV closing sounds performed by Continuous Wavelet Transform (CWT) analysis. Signals were collected from 3 patients immediately after surgery by means of the Myotis 3C, which is a traditional phonocardiographic apparatus. Signals were analyzed by two algorithms: one embedded in the Myotis 3C, based on the Fast Fourier Transform (FFT); and one specifically created for the purposes of the present study, based on CWT. The performance of these algorithms was compared and the results showed that the proposed CWT technique correctly classifies as “double” a large number of clicks that are recognized as “single” by the Myotis 3C.
Fibroblast Growth Factor 23 (FGF23) and the kidney
Authors: Tsagalis George , Psimenou Erasmia , Manios Efstathios , Laggouranis Antonios
Published: January 2018

Phosphate homeostasis in humans is a complex phenomenon involving the interplay of several different organs and circulating hormones. Among the latter, parathyroid hormone (PTH), and vitamin D3 (Vit D3) were thought to be the main regulators of serum phosphate concentration since they mediated the intestinal, renal and bone responses that follow fluctuations in serum phosphate levels. The study of three rare disorders – tumor-induced osteomalacia (TIO), autosomal dominant hypophosphatemic rickets (ADHR) and X-linked hypophosphatemic rickets (XLH) – has offered a completely new insight into phosphate metabolism by unraveling the role of a group of peptides that can directly affect serum phosphate concentration by increasing urinary phosphate excretion. Fibroblast growth factor-23 (FGF-23) is the most extensively studied “phosphatonin”. The production, mechanism of action, effects in various target tissues, and its role in common clinical disorders are the focus of this review.
Current Status of Renal Transplantation from Hcv-Positive Donors
Authors: Fabrizi Fabrizio , Messa Piergiorgio , Martin Paul
Published: January 2018

Hepatitis C virus (HCV) infection remains frequent among renal transplant (RT) recipients and has a detrimental effect on patient and graft survival. Accelerated progression of liver disease due to HCV has been implicated in increased mortality after kidney transplantation but additional outcomes have been related to HCV after RT. All HCV-infected kidney transplant candidates should be considered for liver biopsy before RT. HCV infection should not be considered an absolute contraindication to renal transplantation, although the course of HCV-related liver disease is often progressive. Numerous organ procurement organizations have introduced the policy of accepting kidneys from HCV-positive donors for HCV-positive recipients, but this is still controversial. Single-center experiences have not reported adverse effects on the short-term patient and graft survival, however information from large databases has suggested that RT recipients of HCV-positive donors are independently at risk of mortality even in the modern era of immunosuppression. Renal transplantation should be considered using HCV-seropositive grafts for qualified patients with chronic kidney disease (CKD) stage 5 and HCV infection since good information indicates that the transplantation of kidneys from HCV-infected donors results in improved survival compared to wait-listed and dialysis-dependent candidates. A potential risk related to the use of donor HCV-positive kidneys cannot be excluded, and kidneys from HCV-infected donors should be restricted to recipients with evidence of active viremia at the time of kidney transplantation.
Occupational Stress is Associated with Impaired Work Ability and Reduced Quality of Life in Patients with Chronic Kidney Failure
Authors: Neri Luca , Rey Lisa A. Rocca , Gallieni Maurizio , Brancaccio Diego , Cozzolino Mario , Colombl Antonio , Burroughs Thomas E.
Published: January 2018

Background

About 300,000 patients in the United States with Chronic Kidney Failure (CKF) are of working age, but up to 70% lose their job within the first year of renal replacement therapy. No study has examined how work ability and perceived health are influenced by the subjects’ adjustment to their job. We assessed the association of occupational stress (Effort-Reward Imbalance, ERI), work ability (WAI) and health-related quality of life (QoL) in hemodialysis.

Methods

40 employed hemodialysis patients completed a self-administered questionnaire. Associations between ERI, Short Form 12 (SF-12), Short Form - 6 Dimensions (SF-6D), Kidney Disease QOL - 36 (KDQOL-36) and WAI were tested with partial Spearman's correlation adjusted for age, income, and comorbidity burden.

Results

Study subjects were mainly low-income (82%), African-American (73%), men (75%); 16 were manual laborers and 9 worked in the industrial sector. Study subjects reported low levels of Occupational Stress: ERI scores indicated an imbalance between Job Efforts and Rewards in only 3 subjects. Nevertheless, ERI scores were inversely and strongly associated with WAI (ρ=-0.41, p<0.012) and all QoL scales even after adjustment for known confounders.

Conclusion

Our study suggests that psychosocial workplace factors may play a substantial role in modulating patients’ health perception and ability to continue working. The causal relationship between Occupational Stress, perceived health, and work ability should be further investigated. Occupational Health professionals and nephrologists should closely collaborate to meet the needs of occupationally active hemodialysis patients.
Application of Rituximab to Hepatitis C-Positive, ABO-Incompatible Renal Transplantation
Authors: Tsai Meng-Kun , Yang Ching-Yao , Wu Ming-Shiou , Lee PO-HUANG
Published: January 2018

A safety issue has been noted in applying rituximab to renal transplant patients with HCV infection, as a hepatitis C virus (HCV) flare-up and lethal cholestatic hepatitis C occurred in a renal transplant patient treated with rituximab for lymphoproliferative disorder. As double-filtration plasma-pheresis (DFPP) and cyclosporine were reported to reduce hepatitis C viremia, we performed ABO-incompatible renal transplantation in two patients with positive HCV RNA by using rituximab, DFPP and cyclosporine-based immunosuppressant. The HCV RNA level was 3.3 x 105 lU/mL for Case 1 and 1.2 x 103 lU/mL for Case 2 before DFPP. After DFPP and renal transplantation, Case 1 had stable ALT levels and a transient decrease in HCV RNA to 7.9 x 104 lU/mL at 1 month followed by a gradual increase to 7.6 x 106 at 12 months, but Case 2 had a dramatic and persistent elevation of HCV RNA to 7.7 x 106 from 1 week to 12 months accompanied by elevated ALT levels. The serum creatinine levels were 1.5 mg/dL for Case 1 and 1.9 mg/dL for Case 2 at 12 months. Although cholestatic hepatitis C did not occur in our patients, who received rituximab for ABO-incompatible renal transplantation, the antiviral effect of cyclosporine and DFPP did not seem evident.
Identification of Key Factors in Deep O2 Cell Perfusion for Vascular Tissue Engineering
Authors: Cheema Umber , Hadjipanayi Ektoras , Tamimi Noor , Alp Burcak , Mudera Vivek , Brown Robert A.
Published: January 2018

Blood vessel engineering requires an understanding of the parameters governing the survival of resident vascular smooth muscle cells. We have developed an in vitro, collagen-based 3D model of vascular media to examine the correlation of cell density, O2 requirements, and viability. Dense collagen sheets (100 μxm) seeded with porcine pulmonary artery smooth muscle cells (PASMCs) at low or high (11.6 or 23.2x106 cells/mL) densities were spiraled around a mandrel to create tubular constructs and cultured for up to 6 days in vitro, under both static and dynamic perfusion conditions. Real-time in situ monitoring showed that within 24 hours core O2 tension dropped from 140 mmHg to 20 mmHg and 80 mmHg for high and low cell density static cultures, respectively, with no significant cell death associated with the lowest O2 tension. A significant reduction in core O2 tension to 60 mmHg was achieved by increasing the O2 diffusion distance of low cell density constructs by 33% (p<0.05). After 6 days of static, high cell density culture, viability significantly decreased in the core (55%), with little effect at the surface (75%), whereas dynamic perfusion in a re-circulating bioreactor (1 ml/min) significantly improved core viability (70%, p<0.05), largely eliminating the problem. This study has identified key parameters dictating vascular smooth muscle cell behavior in 3D engineered tissue culture.
Functional Evaluation of the Endotics System, a New Disposable Self-Propelled Robotic Colonoscope: in vitro tests and clinical trial
Authors: Cosentino Felice , Tumino Emanuele , Passoni Giovanni Rubis , Morandi Elisabetta , Capria Alfonso
Published: January 2018

Objective

Currently, the best method for CRC screening is colonoscopy, which ideally (where possible) is performed under partial or deep sedation. This study aims to evaluate the efficacy of the Endotics System, a new robotic device composed of a workstation and a disposable probe, in performing accurate and well-tolerated colonoscopies. This new system could also be considered a precursor of other innovating vectors for atraumatic locomotion through natural orifices such as the bowel. The flexible probe adapts its shape to the complex contours of the colon, thereby exerting low strenuous forces during its movement. These novel characteristics allow for a painless and safe colonoscopy, thus eliminating all major associated risks such as infection, cardiopulmonary complications and colon perforation.

Methods

An experimental study was devised to investigate stress pattern differences between traditional and robotic colonoscopy, in which 40 enrolled patients underwent both robotic and standard colonoscopy within the same day.

Results

The stress pattern related to robotic colonoscopy was 90% lower than that of standard colonoscopy. Additionally, the robotic colonoscopy demonstrated a higher diagnostic accuracy, since, due to the lower insufflation rate, it was able to visualize small polyps and angiodysplasias not seen during the standard colonoscopy. All patients rated the robotic colonoscopy as virtually painless com-pared to the standard colonoscopy, ranking pain and discomfort as 0.9 and 1.1 respectively, on a scale of 0 to 10, versus 6.9 and 6.8 respectively for the standard device.

Conclusions

The new Endotics System demonstrates efficacy in the diagnosis of colonic pathologies using a procedure nearly completely devoid of pain. Therefore, this system can also be looked upon as the first step toward developing and implementing colonoscopy with atraumatic locomotion through the bowel while maintaining a high level of diagnostic accuracy.
New Concepts and New Weapons in Implant Infections
Authors: Arciola Carla Renata
Published: January 2018

Molecular studies have cast light on new facts about the virulence factors of bacteria responsible for implant infections. Recently, the biofilm matrix has been shown to include a variety of important structural components, including DNA, in addition to polysaccharides and proteins. This finding has stimulated interest in substances able to disrupt biofilms by attacking both the poly-N-acetylglucosamine surface polysaccharide (PNAG) and the extracellular DNA (eDNA), namely, dispersin B, a PNAG-degrading enzyme, and DNase I. The therapeutic potential of these enzymes are reviewed in this issue of IJAO, as well as the ability of the excretions/secretions of the medicinal maggot Lucilia sericata to disrupt Staphylococcus epidermidis biofilms. The activity of bacterial proteases causes the release of eDNA, critical for the early development of biofilms. This complex process, including suicidal and fratricidal mechanisms, is also presented in the current issue of IJAO.

The different sensitivities of S. aureus and S. epidermidis to enzymatic anti-biofilm agents and to the host's first line of defense, as well as the importance of knowing the cascade of regulatory genes in bacteria so as to interfere with biofilm production using gene therapy or quorum sensing inhibitors are also discussed in this issue. Other innovative approaches consist in disrupting biofilms by exposing them to photodynamic substances and simultaneously to visible light, and in coating biomaterial surfaces with organic molecules to prevent protein adsorption and biofilm formation.
Therapeutic Potential of Biofilm-Dispersing Enzymes
Authors: Kaplan Jeffrey B.
Published: January 2018

Surface-attached colonies of bacteria known as biofilms play a major role in the pathogenesis of medical device infections. Biofilm colonies are notorious for their resistance to antibiotics and host defenses, which makes most device infections difficult or impossible to eradicate. Bacterial cells in a biofilm are held together by an extracellular polymeric matrix that is synthesized by the bacteria themselves. Enzymes that degrade biofilm matrix polymers have been shown to inhibit bio film formation, detach established bio film colonies, and render biofilm cells sensitive to killing by antimicrobial agents. This review discusses the potential use of biofilm matrix-degrading enzymes as anti-biofilm agents for the treatment and prevention of device infections. Two enzymes, deoxyribonuclease I and the glycoside hydrolase dispersin B, will be reviewed in detail. In vitro and in vivo studies demonstrating the anti-biofilm activities of these two enzymes will be summarized, and the therapeutic potential and possible drawbacks of using these enzymes as clinical agents will be discussed.
The Photodynamic Effect of Tetra-Substituted N-Methyl-Pyridyl-Porphine Combined with the Action of Vancomycin or Host Defense Mechanisms Disrupts Staphylococcus Epidermidis Biofilms
Authors: Sbarra Maria S. , Arciola Carla R. , Di Poto Antonella , Saino Enrica , Rohde Holger , Speziale Pietro , Visai Livia
Published: January 2018

The skin commensal and opportunistic pathogen Staphylococcus epidermidis is an important cause of nosocomial infections. Virulence is attributable to formation of biofilm, which provides a microenvironment that protects the bacterium from attack by the host immune system and by chemotherapy. In this study we extended to S. epidermidis strategies previously aimed at treatment of S. aureus bio films using photodynamic treatment (PDT) combined with chemotherapy or phagocytosis. A significant reduction in bacterial survival was observed when structurally distinct biofilms were exposed to the cationic porphyrin, tetra-substituted N-methyl-pyridyl-porphine (TMP), and simultaneously to visible light. Of note, the extent of biofilm clearance depended on its maturation stage: developing, young biofilms, were more sensitive towards PDT than mature biofilms. Furthermore, PDT-treated biofilms exposed to vancomycin or subjected to phagocytic action of whole blood were almost completely eradicated. The data we obtained establish that PDT combined with antibiotics or host defenses may also be a useful approach for the inactivation of S. epidermidis biofilms.
TRAP Plays a Role in Stress Response in Staphylococcus Aureus
Authors: Kiran Madanahally D. , Balaban Naomi
Published: January 2018

Staphylococci are common pathogens of implant-related infections. RIP is a heptapeptide (YSPWTNF-NH2) that was shown to be very effective in preventing and treating antibiotic-resistant staphylococcal infections, in healing polymicrobial wounds, and in enhancing the effect of commonly used antibiotics. How the peptide negatively affects the survival of the bacteria in the host is not yet known. In staphylococci, RIP was shown to suppress toxin production by inhibiting the expression of agr and production of RNAIII. RIP was also shown to suppress the phosphorylation of TRAP (target of RNAIII-activating peptide), whose function was not clear. Here we show that mutant S. aureus TRAP- cells were more sensitive to oxidative stress and had higher rates of spontaneous and adaptive (agr) mutations. Furthermore, recombinant TRAP protected DNA from oxidative damage caused by hydroxyl radicals. Put together, these results suggest that TRAP is involved in DNA protection from stress. RIP may thus suppress pathogenesis through multiple independent molecular mechanisms involving both suppression of virulence and suppression of stress response.
Description of a New Group of Variants of the Staphylococcus Aureus Elastin-Binding Protein that Lacks an Entire DNA Segment of 180 bp
Authors: Campoccia Davide , Montanaro Lucio , Ravaioli Stefano , Cangini Ilaria , Speziale Pietro , Arciola Carla Renata
Published: January 2018

The elastin-binding protein (EbpS) is a microbial surface component recognizing adhesive matrix molecule (MSCRAMM) found in Staphylococcus aureus that mediates bacterial cell binding to soluble elastin and tropoelastin. In scientific literature it is well established that the gene encoding for the elastin-binding protein (ebpS) is present in the vast majority of Staphylococcus aureus clinical isolates. The present study aimed at investigating a group of new variant forms of ebpS gene identified in S. aureus clinical strains isolated from implant-related orthopedic infections. A PCR screening for the ebpS gene, conducted on over two hundred S. aureus clinical isolates from implant-related infections revealed the detection of six strains exhibiting an altered amplicon size, shorter than expected. In order to elucidate the sequence changes present in these gene variants, the trait comprised between the primers was analyzed in all six isolates bearing the modification and in four isolates exhibiting the regular amplicon size. A similar form of the ebpS gene, lacking a DNA trait of 180 bp, was confirmed in all six isolates independently of their clonal origin. Interestingly, only three of these isolates, all with type IV polymorphism of the accessory genes regulator (agr) locus, showed exactly the same sequence and, thus, the same pattern of point mutations with respect to reference strains. From nucleotide translation, the corresponding encoded protein was found to lack an entire peptide segment of 60 amino acids. From nucleotide sequence translation, this modification was found to implicate the disappearance of an entire hydrophobic domain, whose functional significance needs to be further investigated.
Perspectives on DNA Vaccines. Targeting Staphylococcal Adhesins to Prevent Implant Infections
Authors: Arciola Carla Renata , Speziale Pietro , Montanaro Lucio
Published: January 2018

DNA vaccines consist of a plasmid DNA genetically engineered to produce one or more proteins able to elicit protective immune responses against virulence factors of infectious pathogens. Once introduced into the cells of the host, a DNA vaccine induces a high production of antigens by the endogenous presence of the peptide codifying gene; improves antigen processing and presentation; may be able to simultaneously co-express multiple antigenic molecules; and, lastly, switches on both humoral and cellular immune responses. In this mini-review, we underscore the advantageous characteristics of DNA vaccines compared with traditional ones and provide summaries of some of the more recent studies on them, mainly focusing the possibility of their use in targeting the staphylococcal adhesins that play a key role in the first adhesive phase of implant infections.
Adhesion of Streptococcus Mutans to Different Restorative Materials
Authors: Poggio Claudio , Arciola Carla R. , Rosti Federico , Scribante Andrea , Saino Enrica , Visai Livia
Published: January 2018

Adherence of oral bacteria to the surface of dental restorative materials is considered an important step in the development of secondary caries and periodontal disease. The aim of this study was to investigate and compare the adherence of different restorative materials to Streptococcus mutans strain (CCUG35176) in order to ascertain possible differences. The materials tested ranged across different classes including: flowable composites (Gradia Direct LoFlo; Filtek Supreme XT Flowable), anterior composites (Gradia Direct Anterior), universal composites (Filtek Supreme XT), packable composites (Filtek Silorane; Filtek P60), glass-ionomers (Fuji IX Gp Extra; Equia) and a control reference material (Thermanox plastic coverlips). Bacterial suspension was deposited onto each material and the adhesion was evaluated trough the colony forming units (CFUs) determination. Packable silorane-based composite was found to be less adhesive than posterior packable composite P60, flowable composites and glass ionomers. The fluoride of glass ionomers did not prevent the attachment of S. mutans; furthermore, after roughness analysis and SEM investigations, the hypothesis that the difference in bacterial adhesion can be determined by the particular surface chemistry of the material itself as well as by different electrostatic forces between bacteria and restorative surfaces must be given serious consideration.
Organ Donation Workshop – a Survey on Nurses’ Knowledge and Attitudes toward Organ and Tissue Donation in Iran
Authors: Aghayaw Hamid Reza , Arjmand Babak , Emami-Razavi Seyed Hassan , Jafarian Ali , Shabanzadeh Ali Reza , Jalali Fatemeh , Goodarzi Parisa , Jebelifar Soheila
Published: January 2018

Purpose

Despite increasing transplantation in Iran, organ shortage and long waiting lists remain major problems in the country. Many publications have demonstrated that the willingness of healthcare professionals to participate in the donation process can improve the donation rate. Since nurses are usually the first people among the healthcare staff to recognize a patient as a potential donor, they have an important role in the procurement of organ and tissue from cadaveric donors. Our objectives were to survey nurses’ knowledge and attitudes toward organ and tissue donation and to examine the effect of having them attend a workshop on organ donation.

Methods

A 39-item questionnaire was completed by 66 nurses, before and after participation in a 1-day organ donation workshop that was held at the Iranian Tissue Bank (in Tehran, Iran). The questionnaire contained demographic data, 29 questions regarding knowledge, and 8 questions on attitudes toward organ and tissue donation.

Results

69.7% women and 30.3% men participated in this study. The mean score for knowledge was 16.89 (SD= 3.33) before and 23.76 (SD=1.66) after the workshop (p=0.000). The mean attitudes score was 4.76 (SD=1.71) before and 5.08 (SD=1.34) after the workshop (p=0.235). Although 63.63% claimed they were willing to have a donation card only 15.15% actually carried one.

Conclusions

This study demonstrated that educational programs can enhance nurses’ knowledge and commitment to the organ donation process and, ultimately, increase the donation rate. Consequently, it is of great importance for organ procurement units to focus on regular training programs for all their healthcare staff.
Telavancin and Hydroxy Propyl-β-Cyclodextrin Clearance during Continuous Renal Replacement Therapy: An in vitro Study
Authors: Patel Jignesh H. , Churchwell Mariann D. , Seroogy Julie D. , Barriere Steven L. , Grio Maricor , Mueller Bruce A.
Published: January 2018

Background/Aims

Telavancin is a lipoglycopeptide antimicrobial agent which has been approved in Europe and has been recently FDA approved in the United States. Telavancin's parenteral solution contains hydroxy propyl-β-cyclodextrin (HP-β-CD) to enhance its solubility. The disposition of telavancin and HP-β-CD during continuous renal replacement therapies (CRRT) has not been previously reported.

Methods

The transmembrane clearances (CLtm) of telavancin and HP-β-CD during continuous hemofiltration and hemodialysis were assessed using an in vitro bovine blood model with AN69 and polysulfone hemodiafilters at varying ultrafiltrate and dialysate flow rates (1, 2, 3, & 6 l/hr).

Results

The mean telavancin sieving coefficient ranged from 0.25 to 0.31 during continuous hemofiltration. At all ultrafiltration rates, no differences were observed in telavancin CLtm between the two hemodiafilter types. For continuous hemodialysis, mean telavancin saturation coefficients ranged from 0.10 to 0.43 and CLtm tended to be higher for the polysulfone hemodiafilter than the AN69 hemodiafilter, especially at higher flow rates. Mean HP-β-CD sieving coefficients ranged from 0.63 to 1.03 and saturation coefficients from 0.63 to 1.38, resulting in a CLtm that was similar to ultrafiltrate and dialysate flow rates.

Conclusion

Telavancin CLtm is dependent on hemodiafilter type, dialysate and ultrafiltration rates. CRRT with high ultrafiltrate or dialysate rates may result in sufficient telavancin clearance to alter telavancin dosing. HP-β-CD clearance by continuous hemodialysis or continuous hemofiltration is substantial and may be sufficient to prevent HP-β-CD accumulation in subjects receiving CRRT. Pharmacokinetic studies conducted in patients receiving CRRT and telavancin are needed to confirm these in vitro findings.
Alginate-Encapsulated Human Hepatoma C3A Cells for use in a Bioartificial Liver Device - The Hybrid-Mds
Authors: Harm Stephan , Strobl Karin , Hartmann Jens , Falkenhagen Dieter
Published: January 2018

Purpose

The aim of this study was to encapsulate C3A cells into alginate microcapsules with an average diameter of ≤ 100 μm, thus enabling them to be recirculated in a bioartificial liver device based on MDS (Microsphere-based Detoxification System) technology. The microcapsules have to be permeable for essential proteins such as albumin.

Methods

C3A cells were encapsulated using alginate. The resulting alginate beads were coated with poly(diallyldimethylammoniumchloride) (pDADMAC) and poly(sodium-p-styrenesulfonate) (pSS). Their mechanical stability was tested by recirculation of the microcapsule suspension, while their permeability was determined by reverse-size exclusion chromatography and by the use of a confocal laser microscope. The metabolic activities of encapsulated C3A cells were compared to freely growing adherent C3A cells in static cultivation models. The metabolic functionality of encapsulated C3A cells in static conditions was compared to encapsulated C3A cells in a dynamic model.

Results

The mean diameter of the resulting microcapsules was 86 μm. Our experiments show that these microcapsules were permeable for albumin and the high flow rate of 600 ml/min in a dynamic model has no influence on the survival and the metabolic activities of the encapsulated cells during the tested time of 24 hours.

Conclusions

Alginate microcapsules containing C3A cells can be used to produce albumin and growth factors in a bioartificial or hybrid liver support system. Thanks to their small diameter, the microcapsules in suspension can be recirculated in the MDS.
Development of a New Combined Test Setup for Accelerated Dynamic pH-Controlled in vitro Calcification of Porcine Heart Valves
Authors: Krings Martin , Kanellopoulou Dimitra , Koutsoukos Petros G. , Mavrilas Dimosthenis , Glasmacher Birgit
Published: January 2018

Fifty years after their first implantation, bioprosthetic heart valves still suffer from tissue rupture and calcification. Since new bioprostheses exhibit a lower risk of calcification, fast and reliable in vitro methods need to be evaluated for testing the application of new anti-calcification techniques. This report describes a modification of the well-known in vitro dynamic calcification test method (Glasmacher et al, Leibniz University Hannover (LUH)), combined with the pH-controlled, constant solution supersaturation (CSS) method (University of Patras (UP)). The CSS method is based on monitoring the pH of the solution and the addition of calcium and phosphate ion solutions through the implementation of two syringe pumps. The pH and the activities of all ions in the solutions are thus kept constant, resulting in higher calcification rates compared to conventional in vitro methods in which solution supersaturation is allowed to decrease without any further control. To verify this hypothesis, five glutaraldehyde preserved porcine aortic valves were tested. Three of the valves were tested according to a free-drift methodology: the valves were immersed in a supersaturated calcification solution, with an initial total calcium times total phosphate product of (CaxP)=10.5 (mmol/L)2 renewed weekly. Two valves were tested by the new pH-controlled loop system, implementing the CSS methodology. All valves were tested for a 4-week period, loaded at 300 cycles per minute, resulting in a total of 12 million cycles at the end of the testing period. The degree of calcification was determined weekly by means of μx-ray, and by conventional, clinical and micro-computer tomography (CT, μCT). The results showed that the valves mineralizing at constant solution supersaturation in vitro yielded higher rates of calcification compared to the valves tested at conditions of decreasing solution supersaturation without any control, indicating the development of a new, accelerated, controllable in vitro calcification method.
Quantifying Recirculation in Extracorporeal Membrane Oxygenation: A New Technique Validated
Authors: Lindstrom Steven J. , Mennen Mark T , Rosenfeldt Franklin L. , Salamonsen Robert F.
Published: January 2018

Rationale

The efficacy of veno-venous extracorporeal membrane oxygenation is limited by the phenomenon of recirculation, which is difficult to quantify. Existing measurement techniques using readily available equipment are unsatisfactory.

Objectives

1) To compare the accuracy of measurements of recirculation made using equations comparing blood oxygen content or saturation alone at different points in an ex vivo circuit; 2) to validate a new step-change technique for quantifying recirculation in vivo.

Methods

Anesthetized greyhound dogs cannulated for veno-arterial support were connected to a circuit that allowed the creation of a known level of recirculation ex vivo and blood oxygen content/saturation monitoring. In two dogs, the accuracy of measurements derived from oxygen content and oxygen saturation were compared. The potential of a new technique for measuring recirculation in vivo by comparing the oxygen content of blood sampled during oxygenator bypass to that following a step-change in circuit oxygenation was demonstrated in a veno-venous pilot study and validated in a three-dog veno-arterial study.

Results

Measurements made using oxygen content versus oxygen saturation showed superior correlation with true recirculation (r2=0.87 vs. 0.64, p<0.0001) and less proportional measurement bias (10.3% vs. 49.8%, p=0.0045). Measurements of recirculation made using a step-change in circuit oxygenation and comparing oxygen content as is required for measuring in vivo recirculation overestimated by only 18.6% (95% CI: 3.9–33.2%) and had excellent correlation with true values (r2=0.89).

Conclusions

1) Measurement of recirculation using oxygen content is superior to that using oxygen saturation alone, which demonstrates significant measurement bias; 2) the novel step-change technique is a sufficiently accurate technique for the measurement of recirculation in animal models.
Two Cases of Silent Superior Vena Cava Syndrome associated with Vascular access and End-Stage Renal Disease
Authors: Pipili Chrisoula , Cholongitas Evangelos , Tzanatos Helen
Published: January 2018

Due to the unavoidable use of indwelling devices and the magnitude of the operative problems encountered, Superior Vena Cava Syndrome (SVCS) has become a serious threat for patients with a history of multiple catheter placements. True diagnosis sometimes is not available due to paucity of symptoms or due to the inadequate considerations of the disease. Particularly in patients with chronic kidney disease, the evidence of central venous occlusion dictates the avoidance of placing peripheral dialysis access in this extremity. In this article, we report two patients (case 1- a patient with end stage renal disease and case 2 - a patient with chronic kidney disease) with silent SVCS related to stenosis resulting from indwelling pacemaker leads. Furthermore, the first patient had an extrinsic factor of compression, a brachial artery pseudoaneurysm - which although it was not causative - it may certainly have contributed to the development of SVCS. The brachial artery pseudoaneurysm restricted even more the flow to cephalic vein and consequently to superior vena cava. Though pacemaker leads have been well identified previously in the literature as a cause of the SVCS, the brachial artery pseudoaneurysm causing extrinsic compression constitutes a novel factor. Through the publication of this paper the awareness of SVCS in these patients shall be definitely enhanced. Moreover, physicians, nurses and patients shall be educated regarding the requirement for peripheral vein presentation in chronic kidney disease.