An organizing center in a planar model of neuronal excitability

The paper studies the excitability properties of a generalized FitzHugh-Nagumo model. The model differs from the purely competitive FitzHugh-Nagumo model in that it accounts for the effect of cooperative gating variables such as activation of calcium currents. Excitability is explored by unfolding a pitchfork bifurcation that is shown to organize five different types of excitability. In addition to the three classical types of neuronal excitability, two novel types are described and distinctly associated to the presence of cooperative variables

Malignant Catarrhal Fever Induced by Alcelaphine herpesvirus 1 Is Associated with Proliferation of CD8+ T Cells Supporting a Latent Infection

Alcelaphine herpesvirus 1 (AlHV-1), carried by wildebeest asymptomatically, causes malignant catarrhal fever (WD-MCF) when cross-species transmitted to a variety of susceptible species of the Artiodactyla order. Experimentally, WD-MCF can be induced in rabbits. The lesions observed are very similar to those described in natural host species. Here, we used the rabbit model and in vivo 5-Bromo-2′-Deoxyuridine (BrdU) incorporation to study WD-MCF pathogenesis. The results obtained can be summarized as follows. (i) AlHV-1 infection induces CD8+ T cell proliferation detectable as early as 15 days post-inoculation. (ii) While the viral load in peripheral blood mononuclear cells remains below the detection level during most of the incubation period, it increases drastically few days before death. At that time, at least 10% of CD8+ cells carry the viral genome; while CD11b+, IgM+ and CD4+ cells do not. (iii) RT-PCR analyses of mononuclear cells isolated from the spleen and the popliteal lymph node of infected rabbits revealed no expression of ORF25 and ORF9, low or no expression of ORF50, and high or no expression of ORF73. Based on these data, we propose a new model for the pathogenesis of WD-MCF. This model relies on proliferation of infected CD8+ cells supporting a predominantly latent infection

Oleuropein or rutin consumption decreases the spontaneous development of osteoarthritis in the Hartley guinea pig.

OBJECTIVE: To assess the potential protective effects of three polyphenols oleuropein, rutin and curcumin, on joint ageing and osteoarthritis (OA) development. DESIGN: Sixty 4-week-old Dunkin-Hartley guinea pigs were randomized into four groups and received daily during 31 weeks either standard guinea pig diet (control group) or a standard guinea pig diet enriched with oleuropein (0.025%), rutin (0.5%) or rutin/curcumin (0.5%/0.25%) association. Biomarkers of OA (Coll2-1, Coll2-1NO2, Fib3-1, Fib3-2, ARGS), as well as inflammation (PGE2) were quantified in the serum. Histological assessments of knee cartilage and synovial membrane were performed at week 4 (five young reference guinea pigs) and week 35. RESULTS: At week 35, guinea pigs in the control group spontaneously developed significant cartilage lesions with mild synovial inflammation. The histological scores of cartilage lesions and synovitis were well correlated with the increased level of serum biomarkers. Histologically, all treatments significantly reduced the cartilage degradation score (P < 0.01), but only oleuropein significantly decreased the synovial histological score (P < 0.05) and serum PGE2 levels (P < 0.01) compared to the control group. Coll2-1 was decreased by rutin and the combination of rutin/curcumin, Fib3-1 and Fib3-2 were only decreased by the rutin/curcumin mixture, while Coll2-1NO2 was significantly decreased by all treatments (P < 0.05). CONCLUSION: Oleuropein and rutin +/- curcumin significantly slowed down the progression of spontaneous OA lesions in guinea pigs. While no additive effect was seen in the curcumin + rutin group, the differential effects of oleuropein and rutin on inflammatory and cartilage catabolic markers suggest an interesting combination for future studies in OA protection

Equations estimating renal function in patients with diabetes

Item does not contain fulltextNo abstract available

Glycaemic control and the risk of mortality in elderly type 2 diabetic patients (ZODIAC-20)

P>Aims: Studies on macrovascular consequences of glucose control in elderly patients (> 75 years) with type 2 diabetes mellitus (T2DM) are lacking. The present study aimed to investigate the relationship between HbA(1c) and mortality in this specific population. Methods: Between 1998 and 1999, 374 primary care patients with T2DM aged older than 75 years participated in the Zwolle Outpatient Diabetes project Integrating Available Care study, a prospective observational study. Early 2009, data on mortality were collected. Updated means for annually measured HbA(1c) values were calculated after a follow-up time of 10 years. Updated mean HbA(1c) was used as a time-dependent covariate in a Cox proportional hazard model. Main outcome measures were all-cause and cardiovascular disease (CVD) mortality. Analyses were performed in strata according to diabetes duration (< 5, 5-11 and >= 11 years). Results: In the group with a diabetes duration < 5 years, an increase of 1% in the updated mean HbA(1c) level was associated with an increase in all-cause and CVD mortality risk of 51% (95% CI 17-95%) and 72% (95% CI 19-148%), respectively. Glycaemic control was not related to mortality for patients with a diabetes duration >= 5 years. Conclusion: Poor glycaemic control is related to increased all-cause and CVD mortality in patients > 75 years with T2DM of short duration (< 5 years). Discussion: Because of the observational study design, our results should be interpreted with caution. Nevertheless, they are suggestive that improving glycaemic control may be beneficial in elderly patients with T2DM, especially in those with recently diagnosed T2DM. Randomised-controlled trials are necessary to investigate whether this holds true

[Employing age-related cut-off values results in fewer patients with renal impairment in secondary care]

Item does not contain fulltextOBJECTIVE: To describe the consequences on the burden for primary and secondary care in the Netherlands, of using age-related cut-off values for renal function which follow the Dutch national transmural agreement (LTA) for 'Chronic renal impairment', rather than the 'Kidney disease outcome quality initiative' (K/DOQI) guidelines. DESIGN: Observational cross-sectional study. METHODS: 82,424 patients whose serum creatinine had been determined in 2009 were identified from the laboratory registry of the Isala Clinics in Zwolle, the Netherlands. The glomerular filtration rate was estimated using the abbreviated Modification of Diet in Renal Disease (MDRD) equation (eGFR). Burden of care was defined as the necessity for referral or consultation in secondary care. The number of people that would have been referred using the K/DOQI guideline that refers all those with an eGFR 65 years. 19% of the population (n = 15,637) had an eGFR 65 years. The use of the LTA for 'Chronic renal impairment', that includes age as one of the criteria, would have resulted in the referral of 3,303/15,637 patients (2,011 of those 3,303 were > 65 years), and resulted in consultation with a nephrologist for 5,748/15,637 patients (3,338/5,748 were > 65 years). The majority of patients aged > 65 years and with an eGFR < 60 ml/min/1.73 m2 (55%) could be treated in primary care without consultation of secondary care or referral. CONCLUSION: The categorization applied by the current LTA for 'Chronic renal impairment', whereby age-related cut-off values are used in the referral policy, will result in more targeted referral to secondary care, especially in the elderly patient group, when compared to application of the K/DOQI guidelines

The Cockcroft-Gault: a better predictor of renal function in an overweight and obese diabetic population

Background: The performance of the Cockcroft-Gault (CG) equation, the Modification of Diet in Renal Disease (MDRD) formula, and the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) was evaluated in body mass index (BMI) categories. Material and Methods: In this retrospective cohort study in diabetic patients, creatinine clearance was measured by collecting 24-hour urines. Renal function was estimated using the CG, MDRD, and CKD-EPI. The performance of the equations was evaluated using correlation, Krippendorff's coefficient, bias, precision, and accuracy. Results: The bias of the MDRD and CKD-EPI increased from -13.9 ml/min/1.73 m(2) and -14.0 ml/min/1.73 m(2) (BMI < 25 kg/m(2)), respectively, to -31.7 ml/min/1.73 m(2) and -29.6 ml/min/1.73 m(2) (BMI >30 kg/m(2)), respectively. Bias of the CG decreased from -13.4 ml/min (BMI < 25 kg/m(2)) to -3.2 ml/min (BMI > 30 kg/m(2)). With an accepted 30% dispersion, CG had the largest accuracy in the overweight and obese group (76.9 and 76.8%, respectively). The MDRD and CKD-EPI had an accuracy of 45.8 and 34.0% (overweight group), respectively,and 51.9 and 37.3% (obese group), respectively. Conclusions: All renal function prediction equations are biased when used in overweight or obese diabetic populations with preserved renal function. The CG provides the best estimate of kidney function. The limitations of renal function prediction equations should be kept in mind when making clinical decisions

Detection of Helicosporidium spp. in metagenomic DNA

Distinct isolates of the invertebrate pathogenic alga Helicosporidium sp., collected from different insect hosts and different geographic locations, were processed to sequence the 18S rDNA and β-tubulin genes. The sequences were analyzed to assess genetic variation within the genus Helicosporidium and to design Helicosporidium-specific 18S rDNA primers. The specificity of these primers was demonstrated by testing not only on the Helicosporidium sp. isolates, but also on two trebouxiophyte algae known to be close Helicosporidium relatives, Prototheca wickerhamii and Prototheca zopfii. The genus-specific primers were used to develop a culture-independent assay aimed at detecting the presence of Helicosporidium spp. in environmental waters. The assay was based on the PCR amplification of 18SrDNA gene fragments from metagenomic DNA preparations, and it resulted in the amplification of detectable products for all sampled sites. Phylogenetic analyses that included the environmental sequences demonstrated that all amplification products clustered in a strongly supported, monophyletic Helicosporidium clade, thereby validating the metagenomic approach and the taxonomic origin of the produced environmental sequences. In addition, the phylogenetic analyses established that Helicosporidium spp. isolated from coleopteran hosts are more closely related to each other than they are to the isolate collected from a dipteran host. Finally, the phylogenetic trees depicted intergeneric relationships that supported a Helicosporidium-Prototheca cluster but did not support a Helicosporidium-Coccomyxa grouping, suggesting that pathogenicity to invertebrates evolved at least twice independently within the trebouxiophyte green algae