Effect of Arthrospira powders from different producers on the formation of endothelial cell monolayers.

Arthrospira platensis (AP) and some of its derived products have well-established biological activities as antioxidants or as agents to reduce cardiovascular disease risk factors. Furthermore, AP products have gained increasing importance as potential anti-cancer agents. However, the ingredients of the available products vary greatly with the origin, the type of production and processing, which could have significant consequences for their biological effects. Therefore, the composition and biological influence of five distinct AP powders, which were acquired commercially or produced at a public biotechnology institute, were investigated in regard to their endothelialization capacity using a cell impedance- (CI) based measurement method. The study revealed that the AP composition and especially the influence on HUVEC proliferation differed significantly between the five AP powders up to 109%.Thus, it could be shown that the method used allows the reliable detection of quantitative differences in biological effects of different AP preparations.

[Preoperative iron deficiency with/without anemia-an underestimated risk factor?] / Präoperativer Eisenmangel mit/ohne Anämie ­ ein unterschätzter Risikofaktor?

BACKGROUND: Every third surgical patient already suffers from anemia before surgery. The main cause is iron deficiency. OBJECTIVE: This article describes the perioperative risk of iron deficiency with/without anemia and summarizes potential preventive measures. MATERIAL AND METHODS: Presentation of various current original papers, guidelines and own experiences from the German patient blood management network. RESULTS AND CONCLUSION: Preoperative iron deficiency with/without anemia is an underestimated risk factor for perioperative complications. The implementation of preoperative diagnostics and treatment as part of a comprehensive patient blood management reduces complications and increases patient safety.

Influence of highly concentrated fluoride dentifrices on remineralization characteristics of enamel in vitro.

OBJECTIVES: The aim of this in vitro study was to evaluate the role of highly fluoridated dentifrice on remineralization characteristics of lowly and highly pre-demineralized enamel artificial caries lesions. METHODS: Bovine enamel specimens were prepared (pH 4.95; 21 days) and discriminated in either lowly [L] or highly [H] pre-demineralized artificial caries lesions. Specimens with a mean ΔZbaseline,L (95% CI) of 5120 (4995; 5245) vol.% × µm and a mean ΔZbaseline,H of 8187 (8036; 8339) vol.% × µm were selected and randomly allocated to 12 groups (n = 20). Treatments during pH-cycling (28 days; 6 × 60 min demineralization/day) were brushing 2×/day with fluoride-free (0 ppm F- [L0/H0]), 1100 ppm F- [L1100/H1100], 2800 ppm F- [L2800/H2800], 5000 ppm F- [L5000/H5000], 5000 ppm F- + glycerin [L5000 + glycerin/H5000 + glycerin], and 5000 ppm F- + TCP [L5000 + TCP/H5000 + TCP] containing dentifrices. Dentifrice slurries were prepared with deionized water (1:3wt/wt). After cycling specimens presenting lesion surface loss were discarded and for the remaining 202 specimens, transversal microradiographic (TMR) analyses (ΔZpH-cycle/LDpH-cycle) were performed again. Changes in mineral loss (ΔΔZ = ΔZbaseline - ΔZpH-cycle) and lesion depth (ΔLD = LDbaseline - LDpH-cycle) were calculated. RESULTS: Significant differences for ΔΔZ could be found between L0, L1100, and L5000 as well as H0, H1100, and H2800/H5000 (p ≤ 0.01; ANCOVA). Except for 0 ppm F-, higher ΔΔZ could be found in highly compared with lowly demineralized specimens (p ≤ 0.004; ANCOVA). After pH-cycling, a second lesion front could only be observed in H5000 and H5000 + TCP. The correlation between ΔΔZ and F- was moderate for lowly and highly demineralized lesions (rL = 0.591; pL < 0.001; rH = 0.746; pH < 0.001), indicating a fluoride dose response for both. CONCLUSION: For both baseline substrate conditions, a dose response for fluoride could be revealed. CLINICAL SIGNIFICANCE: Remineralization characteristics of enamel directly depended on baseline mineral loss.

Severe Hyperkalemia Complicating Voriconazole Treatment in a Kidney Transplant Recipient With Histoplasmosis: A Case Report.

Voriconazole is an antifungal agent that is commonly used in immunocompromised patients who develop fungal infections. We report a case of severe recurrent hyperkalemia that developed after starting voriconazole for the treatment of histoplasmosis in a kidney transplant patient who was maintained on tacrolimus-based immunosuppression. Hyperkalemia developed despite reducing the tacrolimus dose to maintain levels in a low therapeutic range. Although interactions between azoles and calcineurin inhibitors are widely recognized, this is the 1st report describing new-onset hyperkalemia following initiation of voriconazole in a kidney transplant patient receiving tacrolimus.

Successful treatment of severe ABO antibody-mediated rejection using bortezomib: a case report.

BACKGROUND: Our program for ABO-incompatible renal transplantation includes antigen-specific immunoadsorption (extracorporeal columns with the A or B trisaccharides), rituximab, and standard maintenance immunosuppression. Anti-A or -B titers ≤ 8 in the indirect antiglobulin test (IAT) against panel A1 or B RBC are acceptable for transplantation. CASE REPORT: A previously healthy, 15-month-old girl was diagnosed with Wilms' tumor and proteinuria. Denys-Drash syndrome was confirmed. Bilateral nephrectomy was performed. At 3.5 years of age she received an ABO-incompatible renal transplant from her father (A1 to O). The anti-A titers before transplantation were low. She was treated preoperatively with rituximab, immunoadsorption, immunoglobulin and mycophenolate mofetil (MMF). The maintenance immunosuppression protocol included basiliximab, tacrolimus, MMF, and prednisolone. The initial postoperative course was uncomplicated with rapid normalization of serum creatinine. The anti-A titers started to increase on postoperative day 5 (8 NaCl/16 IAT). Despite daily immunoadsorptions the titers rose to 1024 NaCl/1024 IAT on day 9. Renal function deteriorated and hemodialysis was started. A renal biopsy on day 9 showed acute severe antibody-mediated rejection. Additional treatment with bortezomib was given and after 2 doses the titers started to decline, renal allograft function improved and hemodialysis was stopped. On day 21 posttransplant the titers went down, creatinine was 28 µmol/L, and no more immunoadsorptions were performed. CONCLUSION: By using bortezomib, we were able to successfully reverse a severe ABO antibody-mediated rejection.

[Preventive bone mineral density measurement in postmenopausal women. Differentiation of treatment of recommendations Guidelines of the Umbrella Organization for Osteology ("Dachverband Osteologie")]. / Präventive Knochendichtemessung bei postmenopausalen Frauen. Differenzierung der Therapieempfehlungen der Leitlinien des Dachverbandes Osteologie (DVO).

BACKGROUND: Osteopenia (OP) or osteoporosis (OST) was diagnosed by bone densitometry (DXA) in postmenopausal women free of known skeletal disorders and without acute fracture. DVO guidelines were applied to define therapeutic indication. METHODS: The study included 94 women aged 59-81 years. Fracture or operation ≤12 months, malignant tumor, ovariectomy, and drugs such as cortisone, strontium, fluorides, bisphosphonates, SERMs, estrogens, and steroids were exclusion criteria. The lowest T-score at the spine, femoral neck, or total hip was decisive. The indication for therapy was determined by evaluating age, BMD, and other risk factors. RESULTS: Using the WHO criteria 22.3% (n=21) had normal BMD, 52.1% (n=49) had OP, and 25.6% (n=24) had OST. According to "Dachverband Osteologie" (DVO) guidelines, 28 women (29.8%) of the whole group needed therapy. Of the 28 women receiving therapy, 9 had OP and 19 had OST. Therapy was indicated in 18.4% for OP and 79.2% for OST. CONCLUSION: A preventive measurement of BMD with DXA provides a benefit for postmenopausal women. Combinatory assessment and consideration of other risk factors allows identification of women who might benefit from early treatment.

Adipokine expression in brown and white adipocytes in response to hypoxia.

BACKGROUND: Adipose tissue has emerged as an important endocrine regulator by secreting hormones referred to as adipokines. Recent studies showed that adipose tissue considerably responds to hypoxia. Although the impact of white adipose tissue on regulative processes is established, the importance of brown adipose tissue in adults has emerged just recently. METHODS: Brown (BA) and white adipocytes (WA) were cultured either in the presence of chemical hypoxia-mimetics or under hypoxic atmosphere of 1% oxygen. Expression of hypoxia-inducible factor 1α (HIF- 1α) was assessed by western blot. The expression levels of several known HIF-1α-regulated proteins [vascular endothelial growth factor (VEGF), leptin, adiponectin, and angiotensinogen (AGT)] were quantified. RESULTS: Both chemical hypoxia-mimetics and physical hypoxia led to increased nuclear HIF-1α expression and to decreased cytoplasmatic adiponectin in both cell types. In contrast, VEGF and AGT expression did not change upon hypoxic stimulation. Leptin was exclusively detectable in WA, while uncoupling-protein 1 (UCP-1) was expressed in BA only. CONCLUSIONS: WA and BA are sensitive to hypoxia, in which HIF-1α expression is induced. Protein expression of adiponectin is hypoxia-dependent, whereas AGT, VEGF, leptin, and UCP-1 expression do not change secondary to hypoxia.

Evaluation of three new strategies to fight obesity in families.

Aims. To evaluate 3 strategies to reduce weight in obese families. Research design and methods. 142 obese parents and 119 obese children kept a fat-calorie restriction diet. On top of this diet, the families were randomized in a three-factorial design to one or more of three weight-loss strategies: (1) an additional diet preferring carbohydrates having a low glycemic index (dual diet), (2) financial incentive, and (3) telemonitoring of weight and physical activity. Results. All children improved their BMI-SDS by 0.18 ± 0.25 (P < .001) independently of the weight-loss strategy. In parents, relative losses of weight (kg) were -6.4% versus -4.0% for dual diet versus calorie restriction (P = .029), -6.9% versus -3.4% for with or without financial incentive (P = .002), and -8.0% versus -4.8% for with or without telemonitoring (P = .033). The weight loss after financial incentive plus dual diet plus telemonitoring was -14.4%. Conclusions. All strategies were effective in adults, in particular when combined. Children improved their BMI-SDS regardless of the strategy.

Expression of ATRAP in adipocytes and negative regulation by beta-adrenergic stimulation of JAK/STAT.

Sympatho-adrenergic activity and the renin-angiotensin system are considered critical regulators of obesity and hypertension. The novel angiotensin II type 1 receptor-associated protein (ATRAP) has been demonstrated to modulate angiotensin II signalling in smooth muscle cells and cardiomyocytes. Adipose tissue expresses important renin angiotensin system components and contributes to cardiometabolic disease. However, ATRAP expression and regulation in adipocytes are unknown. We investigated expression of this novel modulator of angiotensin signalling and its regulation by beta-adrenergic receptors. We found ATRAP to be expressed in differentiated brown and white adipocytes. Stimulation of beta-adrenoceptors strongly suppressed ATRAP expression. We hypothesised a role for JAK/STAT signalling elements. Indeed, beta3-adrenergic stimulation robustly stimulated both STAT1 and STAT3 phosphorylation in a time- and dose-dependent manner. This effect was abrogated by inhibition of PKA and JAK2 signalling. Moreover, inhibition of JAK/STAT and PKA signalling reversed the beta3-adrenergic suppression of ATRAP expression. This study provides the first evidence for expression and adrenergic regulation of the angiotensin II signalling modulator ATRAP in adipocytes. Further, it indicates a novel regulatory link between beta-adrenergic and JAK/STAT signalling.

[Comparison of central and peripheral corneal thicknesses between normal subjects and patients with primary open angle glaucoma, normal tension glaucoma and pseudoexfoliation glaucoma]. / Vergleich von zentraler und peripherer Hornhautdicke zwischen Normalprobanden und Patienten mit chronischem Offenwinkelglaukom, Normaldruckglaukom und Pseudoexfoliationsglaukom.

BACKGROUND: While many comparative data are available about central corneal thickness in different types of open angle glaucoma, peripheral corneal thickness has been much less investigated up to now. Thus, the aim of this study was to compare the central and peripheral corneal thicknesses in patients with primary open angle glaucoma (POAG), normal tension glaucoma (NTG) and pseudoexfoliation glaucoma (PEXG) to values of normal subjects. PATIENTS: 104 patients with POAG, 20 patients with NTG, 23 patients with PEXG and 127 normal subjects were investigated with the Orbscan II. The central corneal thickness and the peripheral corneal thickness at 3 mm distance from the centre were determined in 4 quadrants. The acoustic equivalent factor of 0.92 was not used. Patients with eye diseases, patients who had undergone eye surgery or wearers of contact lenses were excluded. Differences were analysed with the Bonferroni-adjusted Mann-Whitney U Test for statistical significance. RESULTS: The median central corneal thickness in POAG was 600 +/- 35 microm, in NTG 577 +/- 31 microm, in PEXG 603 +/- 25 microm and in the control group 606 +/- 38 microm. The difference between NTG and the control group was statistically significant (p = 0.01). Superiorly the peripheral corneal thickness was lower in POAG (670 +/- 47 microm) and NTG (639 +/- 37 microm) compared to the control group (686 +/- 46 microm). Nasally the peripheral corneal thickness was lower in POAG (656 +/- 48 microm), NTG (658 +/- 55 microm) and PEXG (642 +/- 47 microm) compared to the control group (677 +/- 46 microm). Temporally and inferiorly there were only small differences compared to the control group. The differences in peripheral corneal thickness were not statistically significant. DISCUSSION: In accord with literature data the central corneal thickness was lower in patients with normal tension glaucoma compared to normal subjects. Superiorly and nasally the peripheral corneal thickness was lower in patients with open angle glaucoma than in normal subjects which was, however, not statistically significant. To what extent these characteristics of the corneal architecture are relevant for the pathogenesis of open angle glaucomas has to be clarified in further larger trials.

Vitamins are associated with survival in patients with end-stage renal disease: a 4-year prospective study.

BACKGROUND: Patients with end-stage renal disease are at high risk from premature death due mainly to cardiovascular disease and infections. Established risk factors do not sufficiently explain this increased mortality. We, therefore, investigated total mortality prospectively in a single-centre study in patients on hemodialysis and assessed the prognostic value of baseline disease status, laboratory variables including emerging risk factors, and the influence of vitamin treatment. METHODS: Patients (n = 102) were followed-up for 4 years or until death (n = 49). Survival was calculated by the Kaplan-Meier method. Cox-proportional hazards model was used to determine independent predictors of total mortality. RESULTS: The known risk factors age, baseline clinical atherosclerotic disease, low albumin and increased cardiac troponin T were significantly associated with mortality. Patients who received multivitamins during follow-up had a significantly lower mortality risk than those not receiving this treatment (hazard ratio 0.29, 95% confidence interval 0.15-0.56). These associations remained significant after adjustment for age, cardiovascular disease, albumin and cardiac troponin T at baseline. CONCLUSIONS: The present study suggests that multivitamin supplementation in patients with end-stage renal disease is closely associated with reduced mortality due to all causes. These observations have to be validated in randomized clinical intervention trials.

Efficacy of ezetimibe/simvastatin 10/20 and 10/40 mg compared with atorvastatin 20 mg in patients with type 2 diabetes mellitus.

AIM: This randomized, double-blind study evaluated the efficacy of switching from atorvastatin (ATV) 10 mg to ezetimibe/simvastatin (EZE/SIMVA) 10/20 mg, EZE/SIMVA 10/40 mg or doubling the dose of ATV from 10 to 20 mg in patients with type 2 diabetes (T2D). METHODS: Eligible patients had haemoglobin A(1C)< or =10%, were aged > or =18 years and were on ATV 10 mg for > or =6 weeks before study entry. After a 4-week open-label ATV 10 mg run-in, patients were randomized to EZE/SIMVA 10/20 mg (n = 220), EZE/SIMVA 10/40 mg (n = 222) or ATV 20 g (n = 219) daily for 6 weeks. RESULTS: Greater (p < or = 0.001) reductions in low-density lipoprotein cholesterol (LDL-C) (the primary end-point) were achieved by switching to EZE/SIMVA 10/20 mg (26.2%) or 10/40 mg (30.1%) than by doubling the dose of ATV to 20 mg (8.5%). EZE/SIMVA 10/20 mg and 10/40 mg produced greater (p < or = 0.001) reductions in total cholesterol, non-high-density lipoprotein cholesterol (HDL-C) and apolipoprotein B relative to ATV 20 mg. A reduction (p < or = 0.050) in C-reactive protein was observed with EZE/SIMVA 10/40 mg vs. ATV 20 mg. Similar reductions in triglycerides were observed across the three groups, and none of the treatments produced a significant change in HDL-C. A greater (p < or = 0.001) proportion of patients achieved LDL-C <2.5 mmol/l with EZE/SIMVA 10/20 mg (90.5%) and 10/40 mg (87.0%) than with ATV 20 mg (70.4%). Both EZE/SIMVA doses were generally well tolerated, with an overall safety profile similar to ATV 20 mg. CONCLUSIONS: EZE/SIMVA 10/20 and 10/40 mg provided greater lipid-altering efficacy than doubling the dose of ATV from 10 to 20 mg and were well tolerated in patients with T2D.

In heavy drinkers, fatty acid ethyl esters remain elevated for up to 99 hours.

BACKGROUND: Both medical and forensic needs require reliable detection of earlier ethanol intake after the disappearance of ethanol from blood. The esters of ethanol with free fatty acids (FAEEs) are candidate markers of this kind. However, it is unknown whether FAEEs can serve as a marker for a single prior ethanol intake. In addition, the period for which FAEEs are elevated is unknown. Therefore, we measured FAEEs in heavy drinkers admitted to detoxification, and in healthy subjects after a drinking experiment. METHODS: Blood from 30 heavy drinkers was obtained for up to 5 days during a detoxification period in a psychiatric hospital. In addition, 17 healthy subjects who participated in a drinking experiment and who were abstinent thereafter gave blood during a similar time period for analysis of FAEEs. Fatty acid ethyl esters were measured by gas chromatography-mass spectroscopy. RESULTS: Heavy drinkers had much higher ethanol and FAEEs concentrations than healthy subjects; however, in both groups, FAEEs decreased rapidly during the first day. Only in heavy drinkers, elevated concentrations of FAEEs were observed at days 2 to 4. Concentrations of FAEEs were not associated with serum triglycerides or patients' body mass index. CONCLUSIONS: It is concluded that kinetics of FAEEs are different in heavy drinkers compared with healthy subjects and that FAEEs are of limited value for the detection of prior single ethanol intake.

Post-hoc analysis on the CD14 C(-260)T promoter polymorphism and coronary heart disease.

Functional C(-260)--> T polymorphism in the promoter of the CD14 gene has been reported to be associated with coronary heart disease (CHD). The functional role of the polymorphism, however, is still a matter of debate, since several studies have not proved its effect on clinical outcomes associated with atherosclerosis. Cardiovascular-related morbidity and mortality was assessed in a post-hoc approach four years after baseline characterization of patients (male/female n = 36/32) with angiographically proven coronary heart disease. CD14 C(-260)--> T promoter genotype was determined at baseline. Seventeen out of 20 CHD patients with non-lethal cardiovascular events carried at least one T-allele. CD14 T-260 allele carriers have a 3.59-fold (95 % confidence interval: 1.11-6.75) increased risk for non-lethal cardiovascular events (Kaplan-Meier plot: log rank test p = 0.029). All patients with lethal outcomes (n = 6) were also T-allele carriers. Multivariate logistic regression analysis among CHD patients including age, established risk factors and the C(-260)--> T polymorphism as covariates and non-lethal events as a dependent variable confirmed the independent prospective effect of the T-allele on cardiovascular outcomes in this subset. Further evidence is provided for the role of CD14 C(-260)--> T promoter polymorphism as a genetic susceptibility marker of atherosclerosis in patients with an advanced clinical course of the disease. Due to the small sample size and post-hoc character of the study large-scale prospective studies that monitor patients with proven CHD are needed to confirm these findings.

Early recurrence of nephrotic syndrome (immunoglobulin m nephropathy) after renal transplantation successfully treated with combinations of plasma exchanges, immunoglobulin, and rituximab.

In contrast to focal segmental glomerulosclerosis, which is well known to recur early in a renal graft, there are only few cases described with recurrence of immunoglobulin M (IgM) nephropathy after transplantation. We herein describe a patient with early recurrence of IgM nephropathy. A 15-year-old boy with nephrotic syndrome (IgM nephropathy) proceeding to end-stage renal disease was on dialysis before living related renal transplantation. Native kidneys were not removed. Standard immunosuppression including steroids, tacrolimus, and mycophenolate mofetil yielded initially good graft function with the s-creatinine falling to 73 micromol/L. Proteinuria was present on day 1, increasing to 20 g/L after 3 days. S-creatinine increased to 158 micromol/L and urine production diminished. A graft biopsy showed no rejection or glomerulopathy but protein vacuoles were seen within tubular cells indicating massive proteinuria. Treatment with plasma exchanges, immunoglobulin, and steroids was started. Hemodialysis was necessary. Proteinuria improved to 3.5 g/L, but s-creatinine continued to rise and a second graft biopsy showed vascular rejection (Banff type IIA). The patient was treated with antithymocyte globulin and further plasma exchanges. A single dose of rituximab was given. Five months after transplantation the s-creatinine was 67 micromol/L and there was no proteinuria. In this case early recurrence of nephrotic syndrome occurred on the first posttransplant day in combination with later occurring vascular rejection. Successful treatment included a combination of plasma exchanges, rituximab, immunoglobulin, and antithymocyte globulin.

Endocrine and behavioural plasticity in response to juvenile stress in the semi-precocial rodent Octodon degus.

The present study in the South American rodent Octodon degus shows for the first time that the postnatal development of hypothalamic-pituitary-adrenal axis function in this semi-precocial species differs from that of altricial rodents, i.e. rats or mice, in several aspects. Our experiments revealed a particular pattern of hypothalamic-pituitary-adrenal axis activity during the first 3 weeks of life characterized by (i) a period of low plasma glucocorticoid concentrations, during which (ii) brief stress exposure (1 h parental separation) is able to elevate glucocorticoids significantly. In addition, (iii) repeated stress exposure (1 h parental separation daily) during the first 3 weeks of life resulted in females, but not in males, in an attenuated separation-induced increase of glucocorticoids, and a higher behavioural activity in both sexes at postnatal day 21. These data indicate that parental separation early in life acts as a 'strong' stressor in this species, which on the long run can alter endocrine stress response at the time of weaning in a sex-specific manner. These findings support the role of the hypothalamic-pituitary-adrenal axis as one of the key factors mediating the effects of early life stress on the neuronal network and behaviour in O. degus.

Angioplasty catheters: manufacturing and material problems addressed.

This article describes a project to determine the causes of a high failure rate in one manufacturer's percutaneous transluminal coronary angioplasty catheters. Recommendations for optimal production are outlined.