A study on the effects of seasonal solar radiation on exposed populations

In the present study the effects of seasonal solar radiation (summer and winter) on exposed populations of two different age groups (20-25 and 40-55 years old) were investigated. In addition, the effects of external factors, such as hydrogen peroxide (H(2)O(2)) and gamma-irradiation, as well as the repair efficiency of human lymphocytes from these populations, was also evaluated. Our results show that the amount of DNA damage appears to be influenced by the exposure to solar radiation, with the summer exposure being the most damaging. Age was also found to be a significant factor, with the older population being more susceptible to solar radiation than the younger one. Season does not appear to affect the sensitivity to external DNA-damaging agents, while age does. Age was also found to have an effect on the DNA repair capacity of the examined populations.     

Platelet Activating Factor in Heart Failure: Potential Role in Disease Progression and Novel Target for Therapy

Heart failure (HF) is a complex syndrome with cardiac, renal, neurohormonal and sympathetic nervous system’s manifestations, the pathogenesis of which among others is connected to inflammation. PAF has local and systemic effects pertaining to HF progression since it causes a negative inotropic effect, it induces arrhythmias, it induces apoptosis and it is involved in inflammation and atherosclerosis. In the present review the role of PAF in HF will be thoroughly presented along with the relevant data on PAF enzymes and the potential role of PAF metabolic circuit as a novel pharmacological target.     

Effect of traditional Greek Mediterranean meals on platelet aggregation in normal subjects and in patients with type 2 diabetes mellitus

Patients with type 2 diabetes mellitus have increased risk of cardiovascular disease. Epidemiological studies have shown a correlation between diet and incidence of coronary heart disease. The aim of the study is to determine the effect of a traditional Greek Mediterranean diet on platelet aggregation induced by ADP, arachidonic acid (AA), and especially platelet-activating factor (PAF) on patients with type 2 diabetes mellitus as well as on healthy volunteers. The patients were randomized into two subgroups, A and B. The lipid extracts from traditional Greek Mediterranean-type meals were tested in in vivo for their ability to reduce PAF- or thrombin-induced platelet aggregation. The meals with the most potent anti-aggregating activity were chosen for the diet of both subgroup A and healthy subjects and consumed for a period of 28 days, whereas subgroup B kept to their regular diet that was followed before entering the study. Platelet-rich plasma was isolated before and after the diet, and the ability of platelets to aggregate under the aggregating factors was tested. One-month consumption of diet resulted in a significant reduction in PAF- and ADP-induced aggregation of platelets in both groups of healthy volunteers (PAF and ADP, P < .05) and subgroup A (PAF, P < .001; ADP, P < .05), whereas the AA-induced aggregation was not affected. No effect was observed in subgroup B, which followed the standard diet. Thus the consumption of a traditional Greek Mediterranean diet even for a short period can reduce platelet activity in patients suffering from type 2 diabetes mellitus and in healthy subjects.     

Acute resistance exercise attenuates fasting and postprandial triglyceridemia in women by reducing triglyceride concentrations in triglyceride-rich lipoproteins

A single bout of endurance exercise lowers fasting and postprandial triglyceride (TG) concentrations in both men and women, by reducing TG in triglyceride-rich lipoproteins (TRLs). The effect of resistance exercise on TRL-TG metabolism is not known; previous studies only measured total plasma TG concentrations and provide conflicting results. Furthermore, none has specifically examined women. We therefore sought to evaluate the effect of a single bout of resistance exercise on TRL-TG metabolism in women. We measured the concentrations of TG in total plasma and TRLs in the fasting state and during an oral fat tolerance test in five healthy untrained women (age: 32 ± 5 years; body mass index: 21.5 ± 1.7 kg/m²; peak oxygen consumption: 31 ± 4 mL/kg min) in the morning, on two separate occasions: once after a single ~95-min bout of moderate-intensity whole-body resistance exercise (energy expenditure: 2.9 ± 0.1 MJ) and once after an equivalent period of rest, on the preceding afternoon. Fasting plasma TG and TRL-TG concentrations were 22 ± 12 and 40 ± 21% lower, respectively, and postprandial plasma TG and TRL-TG areas-under-the-curve were 24 ± 13 and 27 ± 10% lower, respectively, after exercise than rest (all P values <0.05). Effect sizes ranged from ?0.52 to ?0.90. Non-TRL-TG concentrations in the fasting and postprandial states were not different between trials (P > 0.60). We conclude that a single bout of resistance exercise attenuates fasting and postprandial triglyceridemia in women by reducing TRL-TG concentrations.     

Excellent long term patient and renal allograft survival after ABO-incompatible kidney transplantation:Experience of one center

AIM: To investigate the long-term results of ABOincompatible(ABOi) kidney transplantation in a single center in Greece.METHODS: Thirty consecutive ABOi kidney transplantations were performed from June 2005 to December 2013. All patients received rituximab one month prior to transplantation. Immunoadsorption therapy was performed for the removal of anti-A/B Ig G antibodies until the titer was ≤ 1:16. Additional apheresis sessions were performed post-operatively. Intravenous immunoglobulin and oral immunosuppression consisting of tacrolimus(TAC) in combination with either everolimus or mycophenolate acid was administered. We compared the long term results of our ABOi group to those of a matched group of 30 ABO compatible(ABOc) living kidney recipients with similar baseline characteristics. The ABOc recipients received an immunosuppressive regimen consisting of TAC and mycophenolate acid. All patients in both groups received induction therapy with Basiliximab or Daclizumab, whereas corticosteroids were instituted on the day of surgery. During the followup period, indication biopsies were performed and interpreted by an experienced nephropathologist. The parameters we analyzed included the following: Donor/recipient age, gender, blood type, human leukocyte antigen mismatches, panel reactive antibodies, primary cause of renal failure, mean time on dialysis, immunosuppressive regimen, patient survival, graft outcome, incidence of rejections, surgical and infectious complications.RESULTS: The mean follow-up period was 6 years(range 1 to 9 years). A mean of 5.0 ± 3.0(range 0-14) pre-transplant immunoadsorptions were required in order to reach the target titer. Patient survival in ABOi group in comparison to ABOc group at 1, 3, 5 and 8 years did not differ significantly(100% vs 100%, 96% vs 100%, 92% vs 100% and 92% vs 100%, P = ns). Additionally, graft survival was similar in the two groups at the same time points(100% vs 100%, 96% vs 96%, 92% vs 96% and 81% vs 92%, P = ns). The mean serum creatinine and the estimated glomerular filtration rate by the modification of diet in renal disease formula at 1, 3, 5 and 8 years did not differ significantly between ABOi and ABOc group. None of the patients in the ABOi group developed acute or chronic antibodymediated rejection evidenced by histological signs. Four patients(13.3%) in the ABOi group and 3(10%) in the ABOc group experienced acute cellular rejection, which was treated successfully in all cases. Bacterial and viral infections were also similar between the two groups.CONCLUSION: ABOi kidney transplantation is a safe and effective alternative that enables kidney transplantation in countries with unacceptably long deceaseddonor waiting lists.     

Platelet activating factor (PAF) and activity of its biosynthetic and catabolic enzymes in blood and leukocytes of male patients with newly diagnosed heart failure

ObjectivesTo evaluate platelet activating factor (PAF) levels, its metabolic enzymes activity and its associations with other inflammatory markers in heart failure (HF) patients.Design and methodsPAF, and two of its key biosynthetic enzymes [lyso-PAF acetyltransferase (lyso-PAF-AT) and DTT-insensitive CDP-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT)] along with its catabolic enzymes [PAF-acetylhydrolase (PAF-AH) and lipoprotein-associated phospholipase-A₂ (Lp-PLA₂)] were measured in serum and leukocytes of twelve newly diagnosed male HF patients. Serum CRP, TNF-α, IL-6, sCD14 and CD40L were also determined.ResultsPAF ranged from 0.03 to 5.6 pmol/mL. Median lyso-PAF-AT, PAF-CPT, PAF-AH and Lp-PLA₂ activities were 4.1, 68.42, 644.44 pmol/min/mg protein and 51.42 pmol/min/μL correspondingly. Lyso-PAF-AT and PAF-CPT activities positively correlated with CRP, IL-6 and with each other, whereas PAF-CPT activity correlated with sCD14 and CD40L (P < 0.05).ConclusionsPAF's biosynthetic enzyme activities correlated with inflammatory and immunologic molecules, which are activated in HF. Our study indicates a potential role of PAF in HF patients.     

Renal outcomes in patients with AL amyloidosis: Prognostic factors,renal response and the impact of therapy

A staging system for patients with renal AL amyloidosis, based on eGFR (<50 ml/min/1.73 m²) and proteinuria (≥5 g/day) at diagnosis, as well as criteria for renal progression (≥25% eGFR reduction) and response (≥30% reduction of proteinuria without renal progression) were recently proposed. We validated these criteria in a cohort of 125 patients with renal AL amyloidosis, mostly treated with bortezomib or lenalidomide. We confirmed the prognostic value of the renal staging system but also identified the limitations of renal progression criteria which are based only on eGFR reduction. We identified the ratio of 24h proteinuria to eGFR as a sensitive marker of renal risk which also accounts for changes in both proteinuria and eGFR: 24h proteinuria/eGFR ratio <30 (in mg/ml/min/1.73 m²) was associated with a 2‐year progression to dialysis rate of 0% compared to 9% for a ratio of 31‐99 and 35% for a ratio ≥100 (P < .001). In landmark analysis, patients who achieved a reduction of this ratio by at least 25% or ≤100 (if initially >100) at 3 months had a 2‐year progression to dialysis of 0% vs 24% for patients who either did not reduce to or still had a ratio >100 (P = .001); similar results were obtained by applying the same criteria at 6 months; thus, the evaluation of treatment effect on renal function may be identified early. Furthermore, primary bortezomib‐based therapy was more effective than lenalidomide‐based therapy, in terms of renal outcomes, especially in patients at intermediate renal risk, but without affecting overall survival.     

Dietary choline and betaine intakes in relation to concentrations of inflammatory markers in healthy adults: the ATTICA study

BACKGROUND: Choline and betaine are found in a variety of plant and animal foods and were recently shown to be associated with decreased homocysteine concentrations. OBJECTIVE: The scope of this work was to investigate the associations between dietary choline and betaine consumption and various markers of low-grade systemic inflammation. DESIGN: Under the context of a cross-sectional survey that enrolled 1514 men (18-87 y of age) and 1528 women (18-89 y of age) with no history of cardiovascular disease (the ATTICA Study), fasting blood samples were collected and inflammatory markers were measured. Dietary habits were evaluated with a validated food-frequency questionnaire, and the intakes of choline and betaine were calculated from food-composition tables. RESULTS: Compared with the lowest tertile of choline intake (<250 mg/d), participants who consumed >310 mg/d had, on average, 22% lower concentrations of C-reactive protein (P < 0.05), 26% lower concentrations of interleukin-6 (P < 0.05), and 6% lower concentrations of tumor necrosis factor-alpha (P < 0.01). Similarly, participants who consumed >360 mg/d of betaine had, on average, 10% lower concentrations of homocysteine (P < 0.01), 19% lower concentrations of C-reactive protein (P < 0.1), and 12% lower concentrations of tumor necrosis factor-alpha (P < 0.05) than did those who consumed <260 mg/d. These findings were independent of various sociodemographic, lifestyle, and clinical characteristics of the participants. CONCLUSIONS: Our results support an association between choline and betaine intakes and the inflammation process in free-eating and apparently healthy adults. However, further studies are needed to confirm or refute our findings.     

Severe anemia and neutropenia associated with hyperzincemia and hypercalprotectinemia

Calprotectin, also known as the S100A8/A9 or MRP8/14 complex, is a major calcium-binding protein in the cytosol of neutrophils, monocytes, and keratinocytes. It differs from other S100 proteins in its zinc-binding capacity. The authors describe a 4-year-old girl with severe anemia, neutropenia, inflammation, and severe growth failure. Bone marrow examination showed moderate dyserythropoiesis. No hemolysis, iron deficiency, hemoglobinopathies, immunologic diseases, or autoantibodies were detected. Serum levels of copper and ceruloplasmin were within the normal range, although the serum zinc concentration was markedly increased (310 microg/dL). Urinary zinc excretion and erythrocyte zinc concentrations were within the normal range. Family studies showed normal zinc and copper plasma levels. The patient's plasma calprotectin concentration showed a 6,000-fold increase (2,900 mg/L) compared with normal values. The calprotectin concentration is known to be elevated in many inflammatory conditions but is generally below 10 mg/L and thus far below the levels reported in this patient. The authors describe this case as an inborn error of zinc metabolism caused by dysregulation of calprotectin metabolism, which mainly presented with the features of microcytic anemia and inflammation.     

The Changing Landscape of Pneumocystis Jiroveci Infection in Kidney Transplant Recipients: Single-Center Experience of Late-Onset Pneumocystis Pneumonia

BackgroundPneumocystis jiroveci pneumonia (PCP) is a life-threatening pulmonary infection after kidney transplantation (KTx). Its onset in the current era of modern immunosuppression and of routine use of universal PCP prophylaxis seems to differ from its onset in previous decades in terms of late onset with subtle clinical presentation, indicating a need for increased vigilance.MethodsWe retrospectively studied all KTx recipients from our center who underwent bronchoscopy and bronchoalveolar lavage (BAL) between 2009 and 2018. Of these, all cases with confirmed PCP any time after the first post-KTx year were included in the analysis.ResultsAmong 60 patients with KTx who had undergone bronchoscopy and BAL, 12 cases with late-onset PCP were identified. PCP appeared late at a median of 10.8 (interquartile range, 2.4-15.8) years after transplantation. Patients’ mean age was 59 years, and all were receiving stable low-dose immunosuppression. Most of the patients (67%) had received PCP prophylaxis after KTx. Five out of 12 patients (42%) had concomitant cytomegalovirus (CMV) reactivation at the time of PCP. In almost all cases, clinical presentation was mild. Treatment consisted of trimethoprim-sulfamethoxazole (TMP-SMX) and intravenous corticosteroid administration, and concomitant immunosuppression was temporarily reduced or withdrawn. Outcome was generally good. None of the patients developed respiratory insufficiency or required mechanical ventilation. One patient died as a result of sepsis, and 3 more with preexisting advanced chronic kidney disease subsequently lost their grafts.ConclusionRenal transplant recipients are at risk of late-onset PCP, even at a steady state of low-dose maintenance immunosuppression. Because of its subtle clinical presentation, high suspicion of the disease is warranted. Its early recognition and proper management are essential for a successful outcome.