Disease spectrum in patients with elevated serum tryptase levels.

BACKGROUND: Elevated serum tryptase levels can be a sign of mastocytosis, which is a rare disease associated with systemic and/or skin manifestations. OBJECTIVE: To investigate patients with elevated tryptase levels in regard to their underlying diseases, and to determine whether increased tryptase can be used as a diagnostic marker for underlying mastocytosis. METHODS: In a retrospective study the data of 96 patients with serum tryptase levels higher than 15 µg/L were systematically analysed. In 48 patients control investigations for baseline tryptase were performed. RESULTS: Fifty-three of the 96 patients had tryptase levels ≥20 µg/L. A mere 16% of the 96 patients suffered from mastocytosis and had the highest tryptase levels (P < 0.001). The remaining patients had anaphylaxis (36%), urticaria and angioedema (26%), local reactions to insect bites (4%), drug reactions (3%), or miscellaneous diagnoses (15%). Only 16 of these had acute symptoms at tryptase investigation. In all, 48 patients had a follow up; in 7/48 patients with acute symptoms normal tryptase levels were seen at control investigations, but 41/48 (85%) patients showed continuously elevated tryptase levels >15 µg/L and in 30 patients (62%) even values >20 µg/L; 11 of these patients had anaphylaxis, five urticaria, five other diagnoses and nine patients mastocytosis. CONCLUSION: More than 50% of patients with non-mastocytosis such as urticaria and angioedema, drug or anaphylactic reactions repeatedly had tryptase levels higher than 20 µg/L. Since baseline tryptase >20 µg/L is a minor criterion for mastocytosis, these patients should be inspected for skin lesions of mastocytosis and receive a diagnostic body work-up for systemic mastocytosis including a bone marrow biopsy.

Oxidative Stress and Neurotoxicity of Cadmium and Zinc on Artemia franciscana.

Despite not being redox-active metals, Cd and Zn can disrupt cellular redox homeostasis by acting pro-oxidatively. The aim of this study was to examine the effects of exposure to Zn (14 and 72 mg/L) and Cd (7.7 and 77 mg/L) for 24 and 48 h on oxidative and antioxidative parameters and the activity of glutathione-S-transferase in Artemia franciscana tissue. In addition, the neurotoxicity of the metals was examined by determining the activity of acetylcholinesterase (AChE). In A. franciscana tissue, Cd (0.0026 ± 0.0001 mg/L) was detected only after 48 h of exposure to 77 mg/L Cd. After 24 h, the 14- and 72-mg/L Zn treatments resulted in significant increases in the Zn concentration (0.54 ± 0.026 mg/L (p < 0.01) and 0.68 ± 0.035 (p < 0.0001), respectively) in A. franciscana tissue compared with the control level, and significant increases were also detected after 48 h (0.59 ± 0.02 (p < 0.0001) and 0.79 ± 0.015 (p < 0.0001), respectively). The malondialdehyde (MDA) concentration in the metal-treated samples was increased after 24 h of exposure, whereas after 48 h, an increase in the MDA concentration was detected only with 7.7. mg/L Cd. A significant increase in the H2O2 concentration after 24 h was measured only after treatment with 72 mg/L Zn. The treatment with 7.7 mg/L Cd for 24 h induced a significant increase in the AChE activity, whereas 48 h of treatment with 77 mg/L Cd and 14 mg/L Zn significantly inhibited AChE. The results indicate that lipid peroxidation resulting from metal toxicity may constitute the basis of neurotoxicity.

Modulation of bladder alpha1-adrenergic receptor subtype expression by bladder outlet obstruction.

PURPOSE: alpha1-Adrenergic receptor (alpha1AR) antagonists are effective for relieving obstructive and irritative symptoms in patients with bladder outlet obstruction. While the alpha1aAR is responsible for prostate smooth muscle relaxation and outlet obstruction relief, to our knowledge the mechanisms underlying the relief of irritative symptoms remain to be determined. Therefore, we investigated mechanisms by which bladder alpha1AR subtypes may be involved in this process. MATERIALS AND METHODS: We studied 42 rats, including 6 unoperated controls, 17 sham operated controls and 19 obstructed animals. Animals were characterized for baseline voiding pattern, followed by surgical intervention or sham surgery to establish obstruction (1.09 mm. restricted opening). After 6 weeks to enable the development of detrusor hypertrophy, voiding behavior was reexamined, the animals were sacrificed and bladder tissue was immediately placed in liquid nitrogen. alpha1AR subtype messenger (m)RNA was quantitated using quantitative competitive reverse transcriptase-polymerase chain reaction and protein expression was determined using radioligand binding with the alpha1AR antagonist [125iodine]2-(-[4-hydroxyphenyl]-ethyl-aminomethyl)tetralone (saturation analysis for total alpha1AR density and competition analysis with BMY7378 and 5-methylurapidel to determine alpha1AR subtypes). RESULTS: In this model 6-week surgical obstruction produced a 6.3-fold increase in bladder weight versus sham operation (p <0.001), concurrent with increased voiding frequency versus before obstruction (p <0.004). Although bladder alpha1AR density did not increase overall with obstruction, striking changes in alpha1AR subtype expression occurred. In control animals 70% of alpha1AR mRNA was the alpha1a subtype, 5% were alpha1b and 25% were alpha1d, whereas in obstructed animals bladder alpha1AR expression changed to 23% alpha1a, 2% alpha1b and 75% alpha1d. Changes in alpha1AR mRNA expression were of similar magnitude throughout the bladder dome, mid body and base. Parallel changes were also evident at the protein level with 100% alpha1aAR expression in control animals changing to new onset alpha1dAR expression (mean plus or minus standard error of mean 36% +/- 7%) in animals with a 5-fold or greater increase in bladder weight. CONCLUSIONS: Our findings indicate a remarkable increase in bladder alpha1dAR mRNA and protein expression after 6 weeks of obstruction and resultant detrusor hypertrophy. This finding is potentially important since alpha1dARs have 10 to 100-fold higher affinity for the endogenous neurotransmitter norepinephrine than the alpha1a or alpha1bAR subtypes. These findings imply that targeting alpha1d may provide a new therapeutic approach for controlling bladder irritative symptoms and possibly detrusor overactivity associated with bladder outlet obstruction.