Maximum urine IL-6, plasma IL-6, and urine IL-8 concentrations are positively correlated with the degree of PUUV-induced AKI.

<p>a) maximum urine IL-6 levels b) maximum plasma IL-6 levels c) maximum urine IL-8 levels d) maximum plasma IL-8 levels.</p

Clinical laboratory indicators in study subjects with PUUV nephropathia epidemica.

a<p>AKI = acute kidney injury; severe AKI = >3-fold rise in serum creatinine during acute illness compared to a 6 month baseline value.</p>b<p>Values are median (95% confidence interval of median).</p

Urinary sediment GATA-3 mRNA levels are elevated and T-bet mRNA levels are decreased during acute illness in PUUV-induced severe AKI.

<p>Severe AKI is >3-fold rise in serum Cr during acute illness compared to a 6 month baseline. Illness day 1 is the first calendar day of reported fever. a) Urinary sediment CD3ε mRNA relative expression compared to 2 week baseline value b) Urinary sediment GATA-3 mRNA relative expression compared to 2 week baseline value c) Urinary sediment T-bet mRNA relative expression compared to 2 week baseline value. Symbols and error bars are mean±S.E.</p

Characteristics of study subjects with PUUV nephropathia epidemica.

a<p>AKI = acute kidney injury; severe AKI = >3-fold rise in serum creatinine during acute illness compared to a 6 month baseline value.</p>b<p>Values are median (95% confidence interval of median).</p

Multivariate statistical models for acute kidney injury in study subjects with PUUV nephropathia epidemica.

a<p>Odds ratio (OR) for developing severe PUUV-induced acute kidney injury (AKI) compared to non-severe AKI. Severe AKI = >3-fold rise in serum creatinine during acute illness compared to a 6 month baseline value.</p>b<p>95% confidence interval (CI) for the Odds Ratio.</p>c<p>log₁₀ transformed variable.</p>d<p>White blood cell (WBC).</p>e<p>Linear regression of log₁₀ transformed peak creatinine ratio vs. log₁₀ transformed variables.</p>f<p>95% confidence interval (CI) for the linear regression coefficient.</p

Data_Sheet_1.docx

<p>Neuropeptide Y (NPY) plays an important role in the regulation of energy homeostasis in the level of central and sympathetic nervous systems (SNSs). Genetic silencing of peripheral Y₂-receptors have anti-obesity effects, but it is not known whether pharmacological blocking of peripheral Y₂-receptors would similarly benefit energy homeostasis. The effects of a peripherally administered Y₂-receptor antagonist were studied in healthy and energy-rich conditions with or without excess NPY. Genetically obese mice overexpressing NPY in brain noradrenergic nerves and SNS (OE-NPY^DβH) represented the situation of elevated NPY levels, while wildtype (WT) mice represented the normal NPY levels. Specific Y₂-receptor antagonist, BIIE0246, was administered (1.3 mg/kg/day, i.p.) for 2 or 4.5 weeks to OE-NPY^DβH and WT mice feeding on chow or Western diet. Treatment with Y₂-receptor antagonist increased body weight gain in both genotypes on chow diet and caused metabolic disturbances (e.g., hyperinsulinemia and hypercholesterolemia), especially in WT mice. During energy surplus (i.e., on Western diet), blocking of Y₂-receptors induced obesity in WT mice, whereas OE-NPY^DβH mice showed reduced fat mass gain, hepatic glycogen and serum cholesterol levels relative to body adiposity. Thus, it can be concluded that with normal NPY levels, peripheral Y₂-receptor antagonist has no potential for treating obesity, but oppositely may even induce metabolic disorders. However, when energy-rich diet is combined with elevated NPY levels, e.g., stress combined with an unhealthy diet, Y₂-receptor antagonism has beneficial effects on metabolic status.</p

The correlations of maximum plasma suPAR levels with clinical and laboratory variables reflecting the severity of the infection in 97 patients with acute Puumala hantavirus infection.

<p>Min = minimum, Max = maximum, CRP = C-reactive protein, PTX3 = pentraxin-3, IL-6 = interleukin-6, IDO = indoleamine 2,3-dioxygenase, cf-DNA = cell-free DNA.</p

Line chart showing soluble urokinase-type plasminogen activator receptor (suPAR) maximum (median 8.7 ng/ml, range 4.0–18.2 ng/ml) and convalesce phase concentrations (median 4.7 ng/ml, range 2.4–12.2 ng/ml) in relation to the onset of fever (day 0) in 97 patients with Puumala hantavirus infection (P-value for the difference <0.001).

<p>Short title: Line chart showing suPAR maximum and convalescence concentrations in relation to the onset of fever.</p

Endothelial Nitric Oxide Synthase G894T Polymorphism Associates with Disease Severity in Puumala Hantavirus Infection

<div><p>Introduction</p><p>Hantavirus infections are characterized by both activation and dysfunction of the endothelial cells. The underlying mechanisms of the disease pathogenesis are not fully understood. Here we tested the hypothesis whether the polymorphisms of endothelial nitric oxide synthase, eNOS G894T, and inducible nitric oxide synthase, iNOS G2087A, are associated with the severity of acute Puumala hantavirus (PUUV) infection.</p><p>Patients and Methods</p><p>Hospitalized patients (n = 172) with serologically verified PUUV infection were examined. Clinical and laboratory variables reflecting disease severity were determined. The polymorphisms of eNOS G894T (Glu298Asp, rs1799983) and iNOS G2087A (Ser608Leu, rs2297518) were genotyped.</p><p>Results</p><p>The rare eNOS G894T genotype was associated with the severity of acute kidney injury (AKI). The non-carriers of G-allele (TT-homozygotes) had higher maximum level of serum creatinine than the carriers of G-allele (GT-heterozygotes and GG-homozygotes; median 326, range 102–1041 vs. median 175, range 51–1499 μmol/l; p = 0.018, respectively). The length of hospital stay was longer in the non-carriers of G-allele than in G-allele carriers (median 8, range 3–14 vs. median 6, range 2–15 days; p = 0.032). The rare A-allele carriers (<i>i</i>.<i>e</i>. AA-homozygotes and GA-heterozygotes) of iNOS G2087A had lower minimum systolic and diastolic blood pressure than the non-carriers of A-allele (median 110, range 74–170 vs.116, range 86–162 mmHg, p = 0.019, and median 68, range 40–90 vs. 72, range 48–100 mmHg; p = 0.003, respectively).</p><p>Conclusions</p><p>Patients with the TT-homozygous genotype of eNOS G894T had more severe PUUV-induced AKI than the other genotypes. The eNOS G894T polymorphism may play role in the endothelial dysfunction observed during acute PUUV infection.</p></div

The clinical and laboratory findings in 172 patients with acute Puumala hantavirus infection.

<p>Abbreviation: CRP, C-reactive protein.</p><p>Normal values: CRP < 10 mg/ml, creatinine ≤ 100 μmol/l for males and ≤ 90 μmol/l for females, platelet count 150–360 x 10⁹/l, leukocyte count 3.4–8.2 x 10⁹/l, hematocrit 0.35–0.50 for males and 0.35–0.46 for females.</p><p>*Equals to the onset of illness before the first blood test was taken.</p><p>**Change in weight during hospital stay reflects the fluid accumulation in the body during the oliguric phase.</p><p>The clinical and laboratory findings in 172 patients with acute Puumala hantavirus infection.</p