Enhanced functions of vascular cells on nanostructured Ti for improved stent applications

Vascular tissue possesses numerous nanostructured surface features, but most metallic vascular stents proposed to restore blood flow are smooth at the nanoscale. Thus, the objective of the present study was to determine in vitro vascular cell functions on nanostructured titanium (Ti) compared to conventional commercially pure (c.p.) Ti. Results of this study showed for the first time greater competitive adhesion of endothelial versus vascular smooth muscle cells on nanostructured Ti compared to conventional Ti after 4 hours. Moreover, when cultured separately, increased endothelial and vascular smooth muscle cell density was observed on nanostructured Ti compared to conventional c.p. Ti after 1, 3, and 5 days; endothelial cells formed confluent monolayers before vascular smooth muscle cells on nanostructured Ti. Results also showed greater total amounts of collagen and elastin synthesis by vascular cells when cultured on nanostructured Ti. Since a major mode of failure of conventional vascular stents is the overgrowth of smooth muscle cells compared to endothelial cells, these results suggest that while the functions of both types of vascular cells were promoted on nanostructured c.p. Ti, endothelial cell functions (of particular importance, cell density or confluence) were enhanced over that of vascular smooth muscle cells. Thus, the present in vitro study showed that vascular stents composed of nanometer c.p. Ti particles may invoke advantageous cellular responses for improved stent applications.     

Development of the Croatian model of organ donation and transplantation

During the past ten years, the efforts to improve and organize the national transplantation system in Croatia have resulted in a steadily growing donor rate, which reached its highest level in 2011, with 33.6 utilized donors per million population (p.m.p.). Nowadays, Croatia is one of the leading countries in the world according to deceased donation and transplantation rates. Between 2008 and 2011, the waiting list for kidney transplantation decreased by 37.2% (from 430 to 270 persons waiting for a transplant) and the median waiting time decreased from 46 to 24 months. The Croatian model has been internationally recognized as successful and there are plans for its implementation in other countries. We analyzed the key factors that contributed to the development of this successful model for organ donation and transplantation. These are primarily the appointment of hospital and national transplant coordinators, implementation of a new financial model with donor hospital reimbursement, public awareness campaign, international cooperation, adoption of new legislation, and implementation of a donor quality assurance program. The selection of key factors is based on the authors'' opinions; we are open for further discussion and propose systematic research into the issue.Transplantation is a widely accepted and successful life-saving treatment providing the best therapeutic benefit for hundreds of thousands of patients (1). Unfortunately, many people die while awaiting an organ transplant. A global shortage of organs available for transplantation raises many bioethical concerns, including the dilemma how to allocate limited resources to an unlimited number of needs and thus offer a fair and equal access to organ transplantation to all patients. Great efforts have been made to increase organ donation worldwide, but with only a moderate success in most of the countries. In contrast with this general trend, Croatia has recently experienced a boom in organ donation and transplantation. In 2011, Croatia had the highest rates of utilized cadaveric donors, kidney transplantations, and liver transplantations in the world (2-5) (Figure 1).Open in a separate windowFigure 1The number of kidney transplantations and the number of patients on the waiting list in Croatia between 2008 and 2011.Remarkably, only one decade ago, Croatia was lagging far behind other European countries with a low donation rate (2.7 donors per million population [p.m.p.] in 2000). The continuous improvement of the organization of the Croatian transplant program resulted in a steadily growing donor rate, which reached the highest level in 2011, with 33.6 utilized donors p.m.p (2). We analyzed the factors that might have contributed mostly to this great success.     

Epstein–barr virus associated acute hepatitis with cross‐reacting antibodies to other herpes viruses in immunocompetent patients: Report of two cases

Epstein–Barr virus (EBV) is the causative agent of infectious mononucleosis (IM) which is characterized by the triad of fever, sore throat, and lymphadenopathy. Self‐limited, mild liver function test abnormalities are seen in IM. Acute hepatitis in primary EBV infection is uncommon. Serum transaminases are elevated but are less than fivefold the normal levels in most cases and rarely exceed 10 times the normal levels in primary EBV infections especially in elderly. Laboratory diagnosis of acute EBV infection is by serological assays confirming the presence of EBV viral capsid antigen (VCA) IgM antibodies. Due to antigenic cross‐reactivity with Herpes viruses, serological assays lack specificity; hence specific molecular diagnostic methods are required for confirmation of the etiology. The present report describes two cases of acute hepatitis caused by infection with EBV which had indistinguishable clinical features and biochemical markers from acute hepatitis caused by hepatotropic viruses such as hepatitis viruses A–E. The diagnosis of infection by EBV was confirmed by detection of EBV DNA in blood of both the patients and EBV DNA in the liver tissue of one of the patients. J. Med. Virol. 85:519–523, 2013. © 2013 Wiley Periodicals, Inc.     

Intron 4 polymorphism of the endothelial nitric oxide synthase gene is associated with elevated blood pressure in type 2 diabetic patients with coronary heart disease

The endothelial nitric oxide synthase (eNOS) gene is responsible for constitutive nitric oxide synthesis and arterial vasodilatation. Recently two polymorphisms, the 27-bp repeat sequence in intron 4 and the Glu298Asp substitution in exon 7 of the eNOS gene have been reported to be related to coronary heart disease (CHD). We screened these polymorphisms of the eNOS gene in 308 unrelated nondiabetic subjects with CHD, in 251 unrelated patients with type 2 diabetes with CHD, and in 110 randomly selected healthy subjects without CHD. The 4a and Asp298 allele frequencies of the eNOS gene were 0.19 and 0.36 in nondiabetic patients with CHD, 0.21 and 0.27 in type 2 diabetic patients with CHD, and 0.16 and 0.31 in nondiabetic subjects without CHD (n.s. between the groups). The Asp298 allele in exon 7 of the eNOS gene was not associated with elevated blood pressure in any of the study groups. Among type 2 diabetic patients with CHD the 4a allele in intron 4 of the eNOS gene was associated with elevated levels of systolic (P=0.035) and mean arterial blood pressure (P=0.040). In nondiabetic subjects these associations were not statistically significant. When all study groups were pooled in statistical analysis the 4a allele of the eNOS gene was associated with elevated diastolic (P=0.032) and mean (P=0.030) arterial blood pressure even after adjustment for confounding factors. We conclude that the 4a allele of the eNOS gene is not associated with CHD or type 2 diabetes, but that it is related to elevated blood pressure levels particularly among type 2 diabetic patients with CHD.     

Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is a rare autoimmune disorder. The clinical spectrum of symptoms is diverse; the diagnosis relying on the presence of at least two out of the three main conditions defining the syndrome: chronic mucocutaneous candidiasis, hypoparathyroidism, and Addison''s disease.Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also called autoimmune polyendocrine syndrome type I (APS-1), is a rare organ-specific autosomal recessive disease (OMIM 240300).1–3 Although APECED may occur worldwide, it remains most common in Iranian Jews (1:9,000),4 Sardinians (1:14,500),5–12 Finns (1:25,000),13 Slovenians (1:43,000),14 Norwegians (1:80,000),15 Polish (1:1,29,000),16 and Japanese (1:10,000,000).17 Multiple organ failures in APECED are caused by a progressive loss of tolerance against self-antigens resulting in an immunological attack and secondary destruction of the adrenals, parathyroid glands, β cells of islet of Langerhans,18 stomach, and small intestine.13 Many of the auto-antigens have been identified and characterized.9,12,19     

Biocompatibility properties of a new braided biodegradable urethral stent: a comparison with a biodegradable spiral and a braided metallic stent in the rabbit urethra

OBJECTIVE: To compare the biocompatibility properties of a new braided biodegradable self-reinforced poly-L-lactic acid (SR-PLLA) urethral stent to the former spiral biodegradable SR-PLLA stent and the stainless steel stent in a rabbit model. MATERIALS AND METHODS: In all, 54 male New Zealand White rabbits were anaesthetized and stents inserted into the prostatic urethra, three of each kind for each sample time. The rabbits were killed after 1, 3, 6, 9, 12 or 15 months and light microscopy and scanning electron microscopy used to analyse the effects. RESULTS: The disintegration of the braided SR-PLLA stent was more closely controlled than that of the spiral SR-PLLA stent. The metallic stent induced epithelial hyperplasia and polyposis earlier than the biodegradable stents, and in these rabbits the polyposis disappeared after the disintegration process. There were no differences in the histological analyses between the biodegradable stents, whereas the metallic stents caused the strongest inflammatory reactions. CONCLUSIONS: The braided SR-PLLA urethral stent functioned well in the rabbit urethra and clinical studies are already planned.     

The impact of islet mass,number of transplants,and time between transplants on graft function in a national islet transplant program

The UK islet allotransplant program is nationally funded to deliver one or two transplants over 12 months to individuals with type 1 diabetes and recurrent severe hypoglycemia. Analyses were undertaken 10 years after program inception to evaluate associations between transplanted mass; single versus two transplants; time between two transplants and graft survival (stimulated C-peptide >50 pmol/L) and function. In total, 84 islet transplant recipients were studied. Uninterrupted graft survival over 12 months was attained in 23 (68%) single and 47 (94%) (p = .002) two transplant recipients (separated by [median (IQR)] 6 (3–8) months). 64% recipients of one or two transplants with uninterrupted function at 12 months sustained graft function at 6 years. Total transplanted mass was associated with Mixed Meal Tolerance Test stimulated C-peptide at 12 months (p < .01). Despite 1.9-fold greater transplanted mass in recipients of two versus one islet infusion (12 218 [9291–15 417] vs. 6442 [5156–7639] IEQ/kg; p < .0001), stimulated C-peptide was not significantly higher. Shorter time between transplants was associated with greater insulin dose reduction at 12 months (beta ?0.35; p = .02). Graft survival over the first 12 months was greater in recipients of two versus one islet transplant in the UK program, although function at 1 and 6 years was comparable. Minimizing the interval between 2 islet infusions may maximize cumulative impact on graft function.     

The clinical profile of musculoskeletal injuries in children attending a major hospital in Delhi,India

Background

Children are vulnerable to musculoskeletal injuries both at home and on the street for various reasons. Morbidity and disabilities resulting from these, mostly preventable, injuries, make them a burden to their families and society. The role of various factors associated with injuries is often not documented.

Methods

This prospective study, done on 100 children aged up to 12 years with musculoskeletal trauma, analysed in details, the various modes of injuries.

Results

One in every five patient was a child below 12 years of age. Boys were injured more than girls. Injuries, especially fractures, were most common in the extremities, the upper limb more commonly injured than the lower limb. Most of the injuries occurred at home. The most common mode of injuries was falls that happened while playing both within and outside the home, followed by road traffic accidents. Most injuries occurred during daytime.

Conclusions

Injuries in children were found to be preventable. Small interventions while constructing homes can contribute tremendously to injury prevention and control in children. Parental awareness about the various modes of injury, role of supervised playing and their responsibility towards injury prevention can play a key role in reducing the morbidity associated with childhood fractures.     

Thioredoxin-Interacting Protein Deficiency Protects against Diabetic Nephropathy

Expression of thioredoxin-interacting protein (TxNIP), an endogenous inhibitor of the thiol oxidoreductase thioredoxin, is augmented by high glucose (HG) and promotes oxidative stress. We previously reported that TxNIP-deficient mesangial cells showed protection from HG-induced reactive oxygen species, mitogen-activated protein kinase phosphorylation, and collagen expression. Here, we investigated the potential role of TxNIP in the pathogenesis of diabetic nephropathy (DN) in vivo. Wild-type (WT) control, TxNIP^−/−, and TxNIP^+/− mice were rendered equally diabetic with low-dose streptozotocin. In contrast to effects in WT mice, diabetes did not increase albuminuria, proteinuria, serum cystatin C, or serum creatinine levels in TxNIP^−/− mice. Whereas morphometric studies of kidneys revealed a thickened glomerular basement membrane and effaced podocytes in the diabetic WT mice, these changes were absent in the diabetic TxNIP^−/− mice. Immunohistochemical analysis revealed significant increases in the levels of glomerular TGF-β1, collagen IV, and fibrosis only in WT diabetic mice. Additionally, only WT diabetic mice showed significant increases in oxidative stress (nitrotyrosine, urinary 8-hydroxy-2-deoxy-guanosine) and inflammation (IL-1β mRNA, F4/80 immunohistochemistry). Expression levels of Nox4-encoded mRNA and protein increased only in the diabetic WT animals. A significant loss of podocytes, assessed by Wilms’ tumor 1 and nephrin staining and urinary nephrin concentration, was found in diabetic WT but not TxNIP^−/− mice. Furthermore, in cultured human podocytes exposed to HG, TxNIP knockdown with siRNA abolished the increased mitochondrial O₂⁻ generation and apoptosis. These data indicate that TxNIP has a critical role in the progression of DN and may be a promising therapeutic target.     

Restarting LDLT During COVID-19: Early Results After Restructuring

IntroductionLiving-donor liver transplantation (LDLT) has been mostly suspended and deceased-donor living transplantation activity has been considerably reduced because of coronavirus disease 2019 (COVID-19). We modified our protocols and procedures in line with COVID-19 guidelines. Since the restructuring, we have performed 20 LDLTs. Our study reports the outcomes of these cases and demonstrates the feasibility of LDLT during this pandemic.Materials and MethodsThe changes were influenced by experiences and communications from across the globe. A month-long self-imposed moratorium was spent in restructuring the program and implementing new protocols. Twenty LDLTs were performed between April 18 and September 15 using the new protocols. Our experience includes 2 simultaneous liver-kidney transplants, 1 ABO-incompatible LDLT, and 1 pediatric case (age 11 months).ResultsNineteen patients recovered and 1 patient died. We maintained our postoperative immunosuppression protocol without many changes. Major complications were observed in 30% of recipients but none of the donors. One recipient was infected with COVID-19 during the postoperative period. A donor-recipient couple contracted COVID-19 after discharge from the hospital. All patients recovered from COVID-19 and liver enzymes were unaffected.ConclusionThis study represents a microcosm of experience in LDLT during the COVID-19 era. Outcomes of LDLT are not affected by COVID-19 per se, provided that we make necessary changes.