Survey of the family Russulaceae (Agaricomycetes, Fungi) in Montenegro

The paper shows that there are 84 known species of the family Russulaceae in Montenegro, 39 of them belonging to the genus Lactarius and 45 to the genus Russula

Altered expression of type II sodium/phosphate cotransporter in polycystic kidney disease

Renal phosphate (Pi) absorption is mediated via the type II sodium/Pi cotransporter (NaPi-2) in the brush border membrane (BBM) of proximal tubules. Simultaneous detection of NaPi-2 mRNA by in situ hybridization and of NaPi-2 immunoreactivity by immunohistochemistry was performed to investigate the distribution of the cotransporter in healthy control rats and during progression of autosomal dominant polycystic kidney disease (ADPKD). The purpose of the study was to disclose a relation between proximal tubular cell differentiation and NaPi-2 expression. In controls, NaPi-2 expression was present in the entire proximal tubule. In the Han:SPRD (cy/+) model for ADPKD, the proximal nephron is primarily affected by the cystic changes. Epithelial proliferation and impaired epithelial-matrix interaction result in a loss of cell differentiation that eventually leads to cystic enlargement of the nephron. Normal expression of NaPi-2 in this model was found only in tubules with intact BBM. Loss of BBM and cellular interdigitation were paralleled by the loss of NaPi-2 in situ hybridization and immunoreactive signals. These changes were moderate and focal in 2-mo-old rats and generalized all over the cortex after 8 mo. Advanced renal damage in the older PKD group was associated with mild phosphaturia, which suggests functional insufficiency of tubular NaPi-2 reabsorption. These data show how proliferative changes and loss of tubular epithelial differentiation in ADPKD may prevent functional expression of the NaPi-2 system in the proximal tubule in a rapidly progressive manner. NaPi-2 in proximal tubule BBM is suggested to play an important role in impaired tubular absorption of Pi in renal disease

Pattern of thyroid function during early pregnancy in women diagnosed with subclinical hypothyroidism and treated with l-thyroxine is similar to that in euthyroid controls

BACKGROUND: Subclinical hypothyroidism (SCH) is associated with a higher miscarriage rate. It is unclear how the thyroid function in SCH differs from that in euthyroidism during early pregnancy. We intended to determine the regulation of thyroid function in women with SCH receiving constant l-thyroxine (T4) replacement during early pregnancy as compared to euthyroid controls. METHODS: This was a prospective cohort study with weekly serum sampling in eight women in early pregnancy with SCH and eight euthyroid women from week 5 to week 12 of pregnancy. Thyroid function was assessed before pregnancy. Women with SCH were treated with T4 (50 microg daily) and continued on an unchanged dose until week 12. The following parameters were measured weekly: thyrotropin (TSH), thyroglobulin, thyroxine, triiodothyronine, free thyroxine (FT4), free triiodothyronine (FT3), estradiol, progesterone, human chorionic gonadotropin, and prolactin. RESULTS: Although the pregestational levels of TSH were significantly higher among women with SCH as compared to euthyroid controls, the self-limited estrogen-induced increment of TSH during early pregnancy was similar in both groups. CONCLUSIONS: Although both SCH and ovarian hyperstimulation were associated with an intermediate rise in TSH, the pattern of thyroid function followed similar changes as in euthyroid controls and is unlikely to cause the higher miscarriage rate observed in SCH

FASEB J

Glomerular hypertension is a major determinant advancing progression to end-stage renal failure. Podocytes, which are thought to counteract pressure-mediated capillary expansion, are increasingly challenged in glomerular hypertension. Studies in animal models of glomerular hypertension indicate that glomerulosclerosis develops from adhesions of the glomerular tuft to Bowman's capsule due to progressive podocyte loss. However, the molecular alterations of podocytes in glomerular hypertension are unknown. In this study, we determined the changes in gene expression in podocytes induced by mechanical stress in vitro (cyclic biaxial stretch, 0.5 Hz, 5% linear strain, 3 days) using cDNA arrays (6144 clones). Sixteen differentially regulated genes were identified, suggesting alterations of cell-matrix interaction, mitochondrial/metabolic function, and protein synthesis/degradation in stretched podocytes. The transcript for the matricellular protein osteopontin (OPN) was most strongly up-regulated by stretch (approximately threefold). By reverse transcriptase-polymer chain reaction, up-regulation of OPN mRNA was also detected in glomeruli of rats treated for 2.5 wk with desoxycorticosterone acetate-salt, an animal model of glomerular hypertension. In cultured podocytes, OPN coating induced a motile phenotype increasing actin nucleation proteins at cell margins and reducing stress fibers and focal adhesions. Intriguingly, additional OPN coating of collagen IV-coated membranes accelerated stretch-induced actin reorganization and markedly diminished podocyte loss at higher strain. This study delineates the molecular response of podocytes to mechanical stress and identifies OPN as a stretch-adapting molecule in podocytes

Characterization of a major modifier locus for polycystic kidney disease (Modpkdr1) in the Han:SPRD(cy/+) rat in a region conserved with a mouse modifier locus for Alport syndrome.

The genetic analysis of rodent disease models provides a powerful tool to investigate how modifier loci cause variation in the phenotypic expression of a disease. In order to test the existence of modifier loci influencing polycystic kidney disease (PKD) phenotypes, we derived a backcross between PKD susceptible Han:SPRD(cy/+) and control Brown Norway (BN) rats, and performed a whole-genome scan in 182 PKD affected hybrids showing different grades of disease severity. The genetic dissection of PKD in the cross allowed us to detect a modifier locus, Modpkdr1, on rat chromosome 8 that controls PKD severity, kidney mass and plasma urea concentration. Results from database searches and computational analyses demonstrated that the Modpkdr1 locus shows strong evidence of synteny conservation with human and mouse chromosomal regions controlling kidney diseases, including disease progression of Alport syndrome. Comparative genome mapping also provided an inventory of potential candidate genes for modifier(s) of PKD. Analyses of the coding regions for four strong candidates (Ctsh, Bcl2a1, Trpc1 and Slc21a2) in (cy/+), BN and Lewis rat strains did not reveal sequence variants that could be associated with PKD. The characterization of Modpkdr1 may provide new insights into modulating mechanisms involved in the pathogenesis of PKD that could delay disease progression in humans. It may also have strong implications in the identification of pathophysiological factors common to different renal disorders

Pharmacokinetics of S-ketamine during prolonged sedation at the pediatric intensive care unit

BackgroundS-ketamine is the S(+)-enantiomer of the racemic mixture ketamine, an anesthetic drug providing both sedation and analgesia. In clinical practice, significant interpatient variability in drug effect of S-ketamine is observed during long-term sedation. AimsThe aim of this study was to evaluate the pharmacokinetic variability of S-ketamine in children aged 0-18years during long-term sedation. Twenty-five children (median age: 0.42years, range: 0.02-12.5) received continuous intravenous administrations of 0.3-3.6mg/kg/h S-ketamine for sedation during mechanical ventilation. Infusion rates were adjusted to the desired level of sedation and analgesia based on the COMFORT-B score and Visual Analog Scale. Blood samples were drawn once daily at random time-points, and at 1 and 4hours after discontinuation of S-ketamine infusion. Time profiles of plasma concentrations of S-ketamine and active metabolite S-norketamine were analyzed using nonlinear mixed-effects modeling software. Clearance and volume of distribution were allometrically scaled using the power model. ResultsA total of 86 blood samples were collected. A 2-compartment and 1-compartment model adequately described the PK of S-ketamine and S-norketamine, respectively. The typical parameter estimates for clearance and central and peripheral volumes of distribution were: CLS-KETAMINE=112L/h/70kg, V1(S-KETAMINE)=7.7L/70kg, V2(S-KETAMINE)=545L/70kg, Q(S-kETAMINE)=196L/h/70kg, and CLS-NORKETAMINE=53L/h/70kg. Interpatient variability of CLS-KETAMINE and CLS-NORKETAMINE was considerable with values of 40% and 104%, respectively, leading to marked variability in steady-state plasma concentrations. ConclusionSubstantial interpatient variability in pharmacokinetics in children complicates the development of adequate dosage regimen for continuous sedatio

Procalcitonin levels predict clinical course and progression-free survival in patients with medullary thyroid cancer

Procalcitonin has been well established as an important marker of sepsis and systemic infection. The authors evaluated the diagnostic and predictive value of calcitonin and its prohormone procalcitonin in medullary thyroid cancer