Simultaneous in vivo measurements of intranasal air and mucosal temperature

Nasal cavity volume and blood temperature along the nasal airways, reflecting the mucosal temperature, are considered to be the most important predictors of nasal air conditioning. The purpose of this study was to simultaneously in vivo measure intranasal air as well as mucosal temperature for the first time. Fifteen healthy subjects were enrolled into the study. Two combined miniaturized thermocouples were used for simultaneous recording of intranasal air and mucosal temperature within the anterior turbinate area close to the head of the middle turbinate without interruption of nasal breathing. The highest air and mucosal temperature values were detected at the end of expiration, the lowest values at the end of inspiration. The difference was statistically significant (P < 0.05). The mean mucosal temperature ranged from 30.2 ± 0.9 to 32.2 ± 0.8°C. The mean air temperature ranged from 28.5 ± 1.2 to 34.1 ± 0.7°C. The mean differences between air and mucosal temperature were 1.7 ± 0.5°C after inspiration and 1.9 ± 0.7°C after expiration. Simultaneous measurements of intranasal air and mucosal temperature are practicable. The detected temperature gradient between air and mucosa confirm a relevant heat exchange during inspiration and expiration. This gradient between air and mucosa is obligatory for heat and water exchange to ensure adequate nasal air conditioning.     

BCR mutants deficient in ligand-independent and more sensitive for ligand-dependent signaling

Signal transduction by the B cell antigen receptor (BCR) regulates development, survival and clonal expansion of B cells. The BCR complex comprises the membrane-bound immunoglobulin molecule (mIg) and the Ig-alpha/Ig-beta heterodimer, and was shown to form oligomeric structures. In pervanadate (PV)-treated B cells, multiple proteins are tyrosine phosphorylated upon expression of the BCR, indicating that the BCR can signal in an antigen-independent fashion. We analyzed the signal transduction from BCR mutants which either have an altered heavy chain transmembrane region or lack the Ig-alpha cytoplasmic tail. In comparison to cells expressing the wild-type receptors, those with a mutant BCR respond to PV treatment with reduced and retarded tyrosine phosphorylation of substrate proteins. Conversely, the cells with mutant BCR are more sensitive to stimulation with low doses of antigen. These data suggest that a correctly assembled BCR complex is important for antigen-independent signaling and setting the threshold for antigen-dependent BCR activation.     

Increased sensitivity to N-methyl-D-aspartate receptor-induced excitotoxicity in cerebellar granule cells from interleukin-1 receptor type I-deficient mice

The effects of chronic exposure to excitatory amino acids (EAAs) were examined in cultured cerebellar granule cells (CGCs) from wild type (WT) and interleukin-1 receptor type I (IL-1RI)-deficient mice. After 8 days in culture, the cells were exposed to 100 microM glutamate or 300 microM N-methyl-D-aspartate (NMDA) for 24 h. Analysis of cell viability, as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay and phase-contrast microscopy revealed that CGCs from IL-1RI-deficient mice were more vulnerable to EAAs as compared to the WT controls. The results indicate that IL-1RI signalling is important for neuronal survival. The effect of glutamate on the CGCs from IL-1RI-deficient mice was decreased by the non-competitive NMDA-receptor antagonist MK-801, supporting the involvement of NMDA receptors in the glutamate-induced excitotoxicity.     

Epstein-Barr virus DNA load in cerebrospinal fluid and plasma of patients with AIDS-related lymphoma

Detection of Epstein-Barr virus (EBV) DNA in the cerebrospinal fluid (CSF) is associated with acquired immunodeficiency syndrome (AIDS)-related brain lymphoma. Real-time polymerase chain reaction (PCR) was performed to quantify EBV DNA in CSF and plasma from 42 patients with AIDS-related non-Hodgkin's lymphoma (NHL). Twenty patients had primary central nervous system lymphoma (PCNSL) and 22 systemic NHL, including 12 with central nervous system involvement (CNS-NHL). As controls, 16 HIV-infected patients with other CNS disorders were examined. EBV DNA was detected in the CSF from 16/20 (80%) patients with PCNSL, 7/22 (32%) with systemic NHL, 8/12 (67%) with CNS-NHL, and 2/16 (13%) of the controls. The viral EBV DNA levels were significantly higher in the CSF from patients with PCNSL or CNS-NHL compared to patients with systemic NHL or controls. EBV DNA was detected in plasma from 5/16 (31%) patients with PCNSL, 9/16 (56%) with systemic NHL, 4/9 (44%) with CNS-NHL, and 4/15 (27%) controls. No difference in plasma viral load was found between patient groups. From the patients with CNS-NHL, plasma samples drawn prior to CNS involvement contained significantly higher EBV DNA levels than those from systemic NHL patients without subsequent CNS involvement. EBV DNA levels in the CSF, but not in plasma, from patients treated with antiherpes drugs were significantly lower than in untreated patients. High CSF EBV DNA levels were found in HIV-associated brain lymphomas and the viral load can be clinically useful. High plasma EBV DNA levels might predict CNS involvement in systemic NHL.     

ATP release in human kidney cortex and its mitogenic effects in visceral glomerular epithelial cells

BACKGROUND: In chronic renal failure the sympathetic nervous system is activated. Sympathetic cotransmitters released within the kidney may contribute to the progression of renal disease through receptor-mediated proliferative mechanisms. METHODS: In human renal cortex electrical stimulation induced adenosine 5'-triphosphate (ATP; luciferin-luciferase-assay) and norepinephrine (HPLC) release was measured. ATP release also was induced by alpha1- and alpha2-adrenergic agonists. [3H]-thymidine uptake was tested in human visceral glomerular epithelial cells (vGEC) and mitogen-activated protein kinase (MAPK42/44) activation in vGEC and kidney cortex. The involved P2-receptors were characterized pharmacologically and by RT-PCR. RESULTS: Sympathetic nerve stimulation and alpha-adrenergic agonists induced release of ATP from human kidney cortex. Seventy-five percent of the ATP released originated from non-neuronal sources, mainly through activation of alpha2-adrenergic receptors. ATP (1 to 100 micromol/L) and related nucleotides (1 to 100 micromol/L) increased [3H]-thymidine uptake. The adenine nucleotides ATP, ATPgammaS, ADP and ADPbetaS were about equally potent. UTP, UDP and alpha,beta-methylene ATP had no effect. ATP, ADPbetaS but not alpha,beta-methylene ATP activated MAPK42/44. ATP induced MAPK42/44 activation, and [3H]-thymidine uptake was abolished in the presence of the MAPK inhibitor PD 98059 (100 micromol/L). mRNA for P2X4,5,6,7 and P2Y1,2,4,6,11 were detected in human vGEC by RT-PCR. CONCLUSIONS: In human renal cortex, adrenergic stimulation releases ATP from neuronal and non-neuronal sources. ATP has mitogenic effects in vGEC and therefore the potential to contribute to progression in chronic renal disease. The pattern of purinoceptor agonist effects on DNA synthesis together with the mRNA expression suggests a major contribution of a P2Y1-like receptor.     

Intraperitoneal protein injection in the axolotl: the amphibian kidney as a novel model to study tubulointerstitial activation

BACKGROUND: A substantial body of experimental evidence suggests that protein loading causes activation of proximal tubular epithelial cells with consecutive interstitial fibrosis. These studies have mostly been performed using mammalian in vivo models of glomerular damage or tissue cultures of mammalian tubulointerstitial cells. The kidney of the axolotl contains not only closed nephrons, but also nephrons with ciliated peritoneal funnels called nephrostomes that have access to the peritoneal fluid. Injection of protein into the peritoneal cavity fails to expose closed nephrons to a protein load, but causes selective uptake and transient storage of proteins in tubular epithelial cells of nephrons with nephrostomes. The purpose of the present study was to determine whether (a) the axolotl kidney can be used as a model to assess protein uptake by tubular cells in vivo in the absence of glomerular damage, and (b) this is accompanied by any evidence of tubular epithelial cell activation and interstitial fibrosis. METHODS: Male and female axolotl (80 to 120 g of weight) were given a daily intraperitoneal injection of 1.5 mL endotoxin-free calf serum or saline as control. Kidneys were harvested after 4 or 10 days using perfusion fixation for light microscopy (fibrous tissue stain) and saline perfusion for immunohistochemistry (fibronectin, TGF-beta and collagen I). RESULTS: The findings document selective storage of protein and lipids, progressive with time, in proximal tubular epithelial cells of nephrons draining the coelomic cavity. In addition, progressive focal accumulation of fibrous tissue was noted around protein-storing tubules. Immunohistochemical staining demonstrated the presence of fibronectin and TGF-beta in the tubular epithelial cells and interstitial cells. CONCLUSION: The axolotl kidney provides a novel in vivo model to study tubulointerstitial activation and induction of interstitial fibrosis by protein loading. The findings are independent of alterations of glomerular function that may have potential confounding effects on peritubular hemodynamics, pO2, cell traffic, etc.     

A Swedish case-control network for studies of drug-induced morbidity--acute pancreatitis

OBJECTIVE: To evaluate risk factors - notably drugs - for developing acute pancreatitis. METHODS: A population-based, case-control study, encompassing 1.4 million inhabitants aged 20-85 years from four regions in Sweden between 1 January 1995 and 31 May 1998. A total of 462 cases were hospitalised in surgical departments with their first episode of acute pancreatitis without previously known biliary stone disease. From a population register, 1781 controls were randomly selected. Information was obtained from medical records and through telephone interviews. RESULTS: Fifty-seven percent of the cases were males. An expert group found evidence for biliary stones in 50% of the cases, alcohol intake in 23%, but in 29% neither of these factors were present. In all, "other" factors, e.g. drugs, could have contributed to the development of acute pancreatitis in 52% of the cases. In a multivariate analysis, the adjusted odds ratios (ORs) for H(2) antagonists were 2.4 (95% CI 1.2-4.8) for proton pump inhibitors (PPIs), 2.1 (1.2-3.4) for non-steroidal anti-inflammatory drugs (NSAIDs), 2.3 (1.3-4.0) for those derived from acetic acid and 1.9 (1.1-3.2) for antibacterials for systemic use. Significant ORs were found for a history of gastrointestinal tract disorders [1.5 (1.1-1.9)] and inflammatory bowel disease (IBD) [3.4 (1.5-7.9)]. Smoking was significantly associated with acute pancreatitis [1.7 (1.2-2.1)] and, for those smoking more than 20 cigarettes per day, the OR was 4.0 (2.2-7.5). Alcohol in moderate amounts did not increase the risk, but for those drinking more than 420 g alcohol per week the OR was 4.1 (2.2-7.5). CONCLUSION: In addition to cholelithiasis, smoking and heavy alcohol use, drugs may be an important risk factor for acute pancreatitis.