Ischemic preconditioning inhibits development of edematous cerulein-induced pancreatitis： Involvement of cyclooxygenases and heat shock protein 70

AIM: To determine whether ischemic preconditioning (IP) affects the development of edematous cerulein-induced pancreatitis and to assess the role of cyclooxygenase-1 (COX-1), COX-2, and heat shock protein 70 (HSP 70) in this process, METHODS: In male Wistar rats, IP was performed by clamping of celiac artery (twice for 5 min at 5-min intervals). Thirty minutes after IP or sham operation, acute pancreatitis was induced by cerulein. Activity of COX-1 or COX-2 was inhibited by resveratrol or rofecoxib, respectively (10 mg/kg). RESULTS: IP significantly reduced pancreatic damage in cerulein-induced pancreatitis as demonstrated by the improvement of pancreas histology, reduction in serum lipase and poly-C ribonuclease activity, and serum concentration of pro-inflammatory interleukin (IL)-lp. Also, IP attenuated the pancreatitis-evoked fall in pancreatic blood flow and pancreatic DNA synthesis. Serum level of anti-inflammatory IL-10 was not affected by IP. Cerulein-induced pancreatitis and IP increased the content of HSP 70 in the pancreas. Maximal increase in HSP 70 was observed when IP was combined with cerulein-induced pancreatitis. Inhibition of COXs, especially COX-2, reduced the protective effect of IP in edematous pancreatitis. CONCLUSION: Our results indicate that IP reduces pancreatic damage in cerulein-induced pancreatitis and this effect, at least in part, depends on the activity of COXs and pancreatic production of HSP 70.     

Factors associated with preservation of C-peptide levels at the diagnosis of type 1 diabetes

Aims

The level of C-peptide can identify individuals most likely to respond to immune interventions carried out to prevent pancreatic β-cell damage.The aim of the study was to evaluate factors associated with C-peptide levels at type 1 diabetes (T1D) diagnosis.

Blood activity of Cu/Zn superoxide dismutase, glutathione peroxidase and catalase in Alzheimer's disease: a case-control study

Cu/Zn superoxide dismutase (Cu/Zn SOD), glutathione peroxidase (GPx) and catalase, which are the three main enzymes involved in cellular protection against damage due to oxygen-derived free radicals have been assayed in plasma and erythrocytes obtained from subjects with dementia of the Alzheimer type (DAT) and from controls. Blood samples were obtained from 25 patients with DAT and from age-matched subjects without diagnoses of neurological disease (non-DAT), as well as from younger individuals (reference group). Using appropriate statistical procedures, the three enzyme activities measured in blood of the elderly were decreased if compared to the younger reference group. Moreover, a significant increase in erythrocyte Cu/Zn SOD and catalase activities of DAT patients was observed compared to the non-DAT group. These results are discussed taking the free radical theory of aging into consideration.     

Comparison of N-glycan pattern of recombinant human coagulation factors II and IX expressed in Chinese hamster ovary (CHO) and African green monkey (Vero) cells

The N-glycan patterns of recombinant human coagulation factors II (rF-II) and IX (rF-IX), derived from both transfected Chinese hamster ovary (CHO) cells and African green monkay (Vero) cells produced at industrial scale, were analyzed by binding to carbohydrate-specific lectins and were compared with the glycan structure of human plasma-derived coagulation factors. Human plasma-derived coagulation factors II (hpF-II) and IX (hpF-IX) exhibited complex-type glycan structures with carbohydrate chains capped with (2–6)-sialic acid. Terminal galactose-(1–4)-N-acetylglucosamine units were detected in hpF-IX. Both CHO cell-derived rF-II and rF-IX exhibited complex-type glycosylation and contained (2–3)-sialic acid in addition to terminal galactose-(1–4)-N-acetylglucosamine. Vero cell-derived rF-IX exhibited a complex-type glycan structure similar to that of CHO cell-derived rF-IX. In contrast, rF-II produced by Vero cells exhibited a glycan microheterogeneity composed of hybrid-type glycosylation containing high-mannose structures and complex-type glycosylation containing (2–3)-sialic acid. Galactose-(1–4)-N-acetylglucosamine structures and a low concentration of (2–6)-sialic acid were detected in both microheterogeneity fractions of Vero cell-derived rF-II. Although different in their carbohydrate structures, coagulation factors II and IX obtained recombinantly from both transformed CHO cells and Vero cells exhibited coagulation activities comparable with the plasma-derived proteins.     

A prospective randomized evaluation of three schedules of mesna administration in patients receiving an ifosfamide-containing chemotherapy regimen: sustained efficiency and simplified administration

Chemotherapy with oxazaphosphorines, such as ifosfamide, is often limited by unacceptable urotoxicity. Without uroprotection hemorrhagic cystitis becomes doselimiting. Mesna, a thiol compound, is a drug able to bind the toxic metabolites, forming nontoxic compounds in the urine. A total of 122 patients were enrolled in this study and 228 chemotherapy cycles with an ifosfamide-containing regimen were performed (225 evaluable). Mesna was given at the same total dose as the ifosfamide in all arms. On arm A, mesna was given i. v. in equal doses 15 min before and 4 h and 8 h following the ifosfamide dose. On arm B, mesna was given in three equivalent doses 15 min before (i.v.) and 4 h (i.v.) and 8 h (p.o., double dose) following ifosfamide. On arm C, mesna was given i.v. intwo equal doses given 15 min before and 4 h following. The incidence of urotoxicity was very low (lower than 15%) in the three arms, 0% in A, 1.36% in B and 2.70% in C. All three arms were equally efficient. Schedule C was considered superior to the others, since it was equally effective, simpler and more convenient.     

Percutaneous peripheral interventions in patients with non-ST elevation acute coronary syndromes performed by interventional cardiologists: rationale and results

BACKGROUND: The coexistence of peripheral artery disease (PAD) and multilevel atherosclerosis increases death and stroke rates in patients with coronary artery disease (CAD). Due to many comorbidities these patients are often treated conservatively without revascularisation. AIM: To investigate whether complex percutaneous cardiovascular interventions for CAD and PAD may improve prognosis and long-term outcome in this group of patients. METHODS: We studied consecutive patients treated for symptomatic CAD who also had chronic PAD. The primary cause of hospital admission for all our patients was non-ST elevation acute coronary syndrome (NSTE ACS). All percutaneous peripheral interventions were performed during one hospital stay (index hospitalisation). Major adverse cardio- and cerebrovascular events (MACCE) during follow-up were defined as follows: death (cardiac and non-cardiac), myocardial infarction (MI), urgent revascularisation (surgical or repeat PCI, peripheral percutaneous intervention), stroke/TIA or amputation. RESULTS: We performed 109 interventions in 78 consecutive patients with chronic peripheral artery stenoses and occlusions. The average age was 61.5+/-8.6 years and the majority were males (80%). Preinterventional angiography showed occlusions that involved the common iliac artery in 28 (36%) patients, the external iliac artery in 16 (21%) patients, internal iliac artery in 2 (3%) patients, and superficial femoral artery in 63 (81%) patients. Stenting was performed in half of the patients with a mean stent length of 69.6+/-50.3 mm. An average number of 1.24+/-0.55 stents was used for each lesion. During a mean follow-up of 18 months (range 4 to 42), there were 4 deaths, 3 MIs, 13 repeated percutaneous peripheral interventions due to restenosis in previously treated peripheral lesions, two urgent coronary interventions, two ischaemic strokes, two TIAs and one amputation. The combined follow--up MACCE end-point occurred in 32% of patients. CONCLUSIONS: Patients with concomitant CAD and PAD could safely undergo percutaneous cardiovascular and peripheral interventions. Multilevel intervention is associated with a promising long-term follow-up.     

Association of coronary atherosclerosis with insulin resistance in patients with impaired glucose tolerance

OBJECTIVES: The purpose of the study was to evaluate the role of insulin resistance (IR) in the development of coronary atherosclerosis in patients with impaired glucose tolerance. METHODS AND RESULTS: The study group consisted of 42 patients with impaired glucose tolerance. Based upon coronary angiography the patients were divided into group A--with prior myocardial infarction and critical coronary stenosis (n=20) and group B--without prior myocardial infarction and without critical coronary stenosis (n=22). In each patient glucose disposal rate (GDR) during metabolic clamp, insulinaemia in the fasting state and during the clamp, glycaemia during oral glucose tolerance test (OGTT), BMI and body mass composition were measured. The groups did not differ in age, BMI, percent fat content and distribution, and blood pressure. Fasting insulinaemia (56.7 microU/ml) was higher in group A than in group B (22.3 microU/ml). GDR in group A (2.96 mg/kg b.m./min) was lower than in group B (5.36 mg/kg b.m./min). There was a negative correlation between the number of critically narrowed coronary vessels and GDR in group A. GDR below 3.97 mg/kg b.m./min was found, based on regression analysis, to be a powerful risk factor for myocardial infarction. CONCLUSIONS: The relationship between IR and severity of coronary atherosclerosis implies its unfavourable role in the development of atherosclerosis. The present findings indicate a negative role of IR in the development of myocardial infarction and suggest that it is an independent risk factor, which identifies high-risk patients requiring treatment that would increase tissue insulin sensitivity.     

Apps for IMproving FITness and Increasing Physical Activity Among Young People: The AIMFIT Pragmatic Randomized Controlled Trial

Background

Given the global prevalence of insufficient physical activity (PA), effective interventions that attenuate age-related decline in PA levels are needed. Mobile phone interventions that positively affect health (mHealth) show promise; however, their impact on PA levels and fitness in young people is unclear and little is known about what makes a good mHealth app.

Objective

The aim was to determine the effects of two commercially available smartphone apps (Zombies, Run and Get Running) on cardiorespiratory fitness and PA levels in insufficiently active healthy young people. A second aim was to identify the features of the app design that may contribute to improved fitness and PA levels.

Methods

Apps for IMproving FITness (AIMFIT) was a 3-arm, parallel, randomized controlled trial conducted in Auckland, New Zealand. Participants were recruited through advertisements in electronic mailing lists, local newspapers, flyers posted in community locations, and presentations at schools. Eligible young people aged 14-17 years were allocated at random to 1 of 3 conditions: (1) use of an immersive app (Zombies, Run), (2) use of a nonimmersive app (Get Running), or (3) usual behavior (control). Both smartphone apps consisted of a fully automated 8-week training program designed to improve fitness and ability to run 5 km; however, the immersive app featured a game-themed design and narrative. Intention-to-treat analysis was performed using data collected face-to-face at baseline and 8 weeks, and all regression models were adjusted for baseline outcome value and gender. The primary outcome was cardiorespiratory fitness, objectively assessed as time to complete the 1-mile run/walk test at 8 weeks. Secondary outcomes were PA levels (accelerometry and self-reported), enjoyment, psychological need satisfaction, self-efficacy, and acceptability and usability of the apps.

Results

A total of 51 participants were randomized to the immersive app intervention (n=17), nonimmersive app intervention (n=16), or the control group (n=18). The mean age of participants was 15.7 (SD 1.2) years; participants were mostly NZ Europeans (61%, 31/51) and 57% (29/51) were female. Overall retention rate was 96% (49/51). There was no significant intervention effect on the primary outcome using either of the apps. Compared to the control, time to complete the fitness test was –28.4 seconds shorter (95% CI –66.5 to 9.82, P=.20) for the immersive app group and –24.7 seconds (95% CI –63.5 to 14.2, P=.32) for the nonimmersive app group. No significant intervention effects were found for secondary outcomes.

Conclusions

Although apps have the ability to increase reach at a low cost, our pragmatic approach using readily available commercial apps as a stand-alone instrument did not have a significant effect on fitness. However, interest in future use of PA apps is promising and highlights a potentially important role of these tools in a multifaceted approach to increase fitness, promote PA, and consequently reduce the adverse health outcomes associated with insufficient activity.

Trial Registration

Australian New Zealand Clinical Trials Registry: ACTRN12613001030763; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12613001030763 (Archived by WebCite at http://www.webcitation.org/6aasfJVTJ).     

Influence of MXene (Ti3C2) Phase Addition on the Microstructure and Mechanical Properties of Silicon Nitride Ceramics

This paper discusses the influence of Ti₃C₂ (MXene) addition on silicon nitride and its impact on the microstructure and mechanical properties of the latter. Composites were prepared through powder processing and sintered using the spark plasma sintering (SPS) technic. Relative density, hardness and fracture toughness, were analyzed. The highest fracture toughness at 5.3 MPa·m^1/2 and the highest hardness at HV5 2217 were achieved for 0.7 and 2 wt.% Ti₃C₂, respectively. Moreover, the formation of the Si₂N₂O phase was observed as a result of both the MXene addition and the preservation of the α-Si₃N₄→β-Si₃N₄ phase transformation during the sintering process.