The relationship between clinical phenotype and kallikrein-kinin bioregulation in different forms of arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have shown increased levels of neutrophils generating kallikrein-kinin peptides in blood which are potent mediators of inflammation. This study investigated the association between the bioregulation of kinin-mediated inflammation with the clinical, quality of life, and imaging characteristics (e.g. ultrasonography) of different arthritides. METHODS: Patients with osteoarthritis (OA, n = 29), gout (n = 10) and RA (n = 8) were recruited and screened for clinical symptoms, quality of life, and ultrasonographical assessment of arthritis. Blood neutrophils were assessed for the expression of bradykinin receptors (B1R and B2R), kininogens and kallikreins by immunocytochemistry with visualization by bright field microscopy. Levels of plasma biomarkers were measured by ELISA and cytometric bead array. RESULTS: Quality of life (SF-36 domains and summary scores; including pain; and, HAQ) was similar across OA, gout and RA patients; with the exception of worse physical functioning scores between OA and gout patients. Synovial hypertrophy (on ultrasound) differed between groups (p = 0.001), and the dichotomised Power Doppler (PD) score of greater than or equal to 2 (PD-GE2) was marginally significant (p = 0.09). Plasma IL-8 were highest in patients with gout followed by RA and OA (both, P < 0.05). Patients with RA had higher plasma levels of sTNFR1, IL-1ß, IL-12p70, TNF and IL-6, compared to OA and gout patients (all, P < 0.05). Patients with OA had higher expression of K1B and KLK1 on blood neutrophils followed by RA and gout patients (both, P < 0.05). Bodily pain correlated with B1R expression on blood neutrophils (r = 0.334, p = 0.05), and inversely with plasma levels of CRP (r = -0.55), sTNFR1 (r = -0.352) and IL-6 (r = -0.422), all P < 0.05. Expression of B1R on blood neutrophils also correlated with Knee PD (r = 0.403) and PD-GE2 (r = 0.480), both P < 0.05. CONCLUSIONS: Pain levels and quality of life were similar between patients with OA, RA and gout with knee arthritis. Plasma inflammatory biomarkers and B1R expression on blood neutrophils correlated with pain. Targeting B1R to modulate the kinin-kallikrein system may pose as a new therapeutic target in the treatment of arthritis.

Mass spectrometric study of variation in kinin peptide profiles in nasal fluids and plasma of adult healthy individuals.

BACKGROUND: The kallikrein-kinin system is assumed to have a multifunctional role in health and disease, but its in vivo role in humans currently remains unclear owing to the divergence of plasma kinin level data published ranging from the low picomolar to high nanomolar range, even in healthy volunteers. Moreover, existing data are often restricted on reporting levels of single kinins, thus neglecting the distinct effects of active kinins on bradykinin (BK) receptors considering diverse metabolic pathways. A well-characterized and comprehensively evaluated healthy cohort is imperative for a better understanding of the biological variability of kinin profiles to enable reliable differentiation concerning disease-specific kinin profiles. METHODS: To study biological levels and variability of kinin profiles comprehensively, 28 healthy adult volunteers were enrolled. Nasal lavage fluid and plasma were sampled in customized protease inhibitor prespiked tubes using standardized protocols, proven to limit inter-day and interindividual variability significantly. Nine kinins were quantitatively assessed using validated LC-MS/MS platforms: kallidin (KD), Hyp4-KD, KD1-9, BK, Hyp3-BK, BK1-8, BK1-7, BK1-5, and BK2-9. Kinin concentrations in nasal epithelial lining fluid were estimated by correlation using urea. RESULTS: Circulating plasma kinin levels were confirmed in the very low picomolar range with levels below 4.2 pM for BK and even lower levels for the other kinins. Endogenous kinin levels in nasal epithelial lining fluids were substantially higher, including median levels of 80.0 pM for KD and 139.1 pM for BK. Hydroxylated BK levels were higher than mean BK concentrations (Hyp3-BK/BK = 1.6), but hydroxylated KD levels were substantially lower than KD (Hyp4-KD/KD = 0.37). No gender-specific differences on endogenous kinin levels were found. CONCLUSIONS: This well-characterized healthy cohort enables investigation of the potential of kinins as biomarkers and would provide a valid control group to study alterations of kinin profiles in diseases, such as angioedema, sepsis, stroke, Alzheimer's disease, and COVID-19.

Reproducibility of nasal allergen challenge in evaluating the efficacy of intranasal corticosteroid treatment.

BACKGROUND: Although nasal challenge with allergen has often been used to evaluate the efficacy of therapeutic modalities used for the treatment of allergic rhinitis, the reproducibility of this model in quantitatively evaluating efficacy has not been rigorously examined. OBJECTIVE: To examine the reproducibility of the suppressive effects of an intranasal corticosteroid on the clinical and biochemical outcomes of a nasal allergen challenge during two identical treatment periods using the same subjects. METHODS: In a single-blind study, 25 seasonal allergic subjects with positive skin tests to grass or ragweed were studied outside of their pollen season. Subjects underwent a baseline, three-dose allergen challenge. Beginning 1 week later, subjects received two 7-day courses of intranasal beclomethasone (168 microg b.i.d.) separated by a 1-month washout period. Nasal challenges with allergen were performed after each treatment period. The nasal allergic response was evaluated by counting sneezes, recording symptom scores and measuring levels of albumin (an index of vascular permeability), lysozyme (an index of serous glandular secretion) and kinins (proinflammatory peptides) in recovered nasal lavages. RESULTS: Compared with the baseline challenge, each course of beclomethasone significantly reduced sneezing, symptom scores, albumin and kinins, but not lysozyme. Reproducibility analysis of the net changes from diluent challenge in the two beclomethasone treatment periods, showed the following intraclass correlation coefficients: sneezing (0.92), lysozyme (0.82), symptom scores (0.72), albumin (0.64) and kinins (0.28). CONCLUSION: We conclude that the nasal challenge model is a reproducible method to evaluate the efficacy of anti-allergic medications. For nasal corticosteroid trials, sneezing, symptom scores and albumin levels are recommended as the most reproducibly suppressive outcome measures.

Generation of kinins during preparation and storage of whole blood-derived platelet concentrates.

BACKGROUND: Leukoreduction of platelet (PLT) concentrates (PCs) may be associated with hypotension in recipients, and a role for bradykinin (BK)-related peptides has been proposed for this side effect. STUDY DESIGN AND METHODS: The concentration of BK and one of its vasoactive metabolites, des-arginine(9)-BK (des-Arg(9)-BK), was measured in a large number of PCs as a function of leukoreduction and storage duration with specific enzyme immunoassays and complementary techniques. RESULTS: On Day 0 of storage, kinins were detected in leukoreduced and unfiltered PCs at a concentration lower than 100 pg per mL. During storage, both kinin levels peaked on Day 5 of storage, with a concentration higher than 1 ng per mL in 22 percent of PCs whether filtered on Day 0 or not. Physicochemical and pharmacologic characterizations of immunoreactive kinins confirm their nature. In vitro activation of the contact system of the corresponding PLT-poor plasma showed that a high kinin concentration on Day 5 of the storage corresponded with a low kinin-forming capacity of plasma. On Day 7, BK was no longer elevated presumably due to its degradation and the depletion of kinin-forming capacity of the plasma in stored PCs. The activities of metallopeptidases that metabolize BK-related peptides in plasma from PCs were at levels similar to those recorded in the plasma of a normal reference population and were unaffected by storage. CONCLUSION: Storage of PCs contributes to the hydrolysis of high-molecular-weight kininogen and generation of pharmacologically relevant BK levels that might pose a hazard in susceptible patients.

Actions of kinin peptides in the stomatogastric ganglion of the crab Cancer borealis.

To fully understand neuronal network operation, the influence of all inputs onto that network must be characterized. As in most systems, many neuronal and hormonal pathways influence the multifunctional motor circuits of the crustacean stomatogastric ganglion (STG), but the actions of only some of them are known. Therefore, we characterized the influence of the kinin peptide family on the gastric mill (chewing) and pyloric (filtering of chewed food) motor circuits in the STG of the crab Cancer borealis. The kinins are myoactive in arthropods and they occur within the arthropod central nervous system (CNS), but their CNS actions are not well characterized in any species. The pevkinins were first identified in the shrimp Penaeus vannamei, but they have yet to be studied in the STG of any species. We identified kinin-like immunolabeling (KLI) in the pericardial organs (POs) in C. borealis, but there was no KLI within the STG. The POs are a major source of hormonal influence on the STG. Pevkinin peptides activated the pyloric circuit and they caused a modest increase in the speed of ongoing pyloric rhythms. This modest influence on cycle speed resulted in part from pevkinin excitation of the lateral pyloric neuron, whose strengthened inhibitory synapse onto the pyloric pacemaker neurons limited the pevkinin-mediated increase in cycle speed. The pevkinin excitation of the pyloric rhythm was not strong enough to interfere with the previously documented, gastric mill rhythm-mediated weakening of the pyloric rhythm. Pevkinin also had little influence on the gastric mill rhythm. These results indicate that the kinin peptides have distinct and selective modulatory actions on the pyloric rhythm.

Mass spectrometric analysis of head ganglia and neuroendocrine tissue of larval Galleria mellonella (Arthropoda, Insecta).

A brain-retrocerebral complex-subesophageal ganglion acidified methanolic extract of 100 larval Galleria mellonella (greater wax moth) was prepared for the isolation and identification of (neuro)peptides. To reduce sample complexity, the isolated peptides were roughly separated using a single, conventional chromatographic separation step. Subsequently, screening of these fractions with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in combination with nanoflow electrospray ionization quadrupole time-of-flight tandem mass spectrometry resulted in the identification of 12 lepidopteran peptides. None of these had been previously isolated or characterized within this species. VIFTPKLamide encoded by the diapause hormone-pheromone biosynthesis activating neuropeptide precursor was for the first time isolated and biochemically identified in a tissue extract, providing irrefutable evidence of its expression in larval nervous tissue. Another pentapeptide, AMVRFamide, with no resemblance to other lepidopteran peptides, was de novo sequenced and is most related to the neuropeptide F peptide family.

Plasma prekallikrein: a risk marker for hypertension and nephropathy in type 1 diabetes.

The relevance and significance of the plasma kallikrein/kinin system as a risk factor for the development of vascular complications in diabetic patients was explored in a cross-sectional study. We measured the circulating levels of plasma prekallikrein (PK) activity, factor XII, and high-molecular weight kininogen in the plasma of 636 type 1 diabetic patients from the Diabetes Control and Complications Trial/Epidemiology and Diabetes Intervention and Complications Study cohort. The findings demonstrated that type 1 diabetic patients with blood pressure > or =140/90 mmHg have increased PK levels compared with type 1 diabetic patients with blood pressure <140/90 (1.53 +/- 0.07 vs. 1.27 +/- 0.02 units/ml; P < 0.0001). Regression analysis also determined that plasma PK levels positively and significantly correlated with diastolic (DBP) and systolic blood pressures (SBP) as continuous variables (r = 0.17 and 0.18, respectively; P < 0.0001). In multivariate regression analysis, the semipartial r(2) value for PK was 2.93% for SBP and 2.92% for DBP (P < 0.0001). A positive correlation between plasma PK levels and the urinary albumin excretion rate (AER) was also observed (r = 0.16, P < 0.0001). In categorical analysis, patients with macroalbuminuria had a significantly higher level of plasma PK than normoalbuminuric patients (1.45 +/- 0.08 vs. 1.27 +/- 0.02 units/ml; P < 0.01), whereas microalbuminuric patients had an intermediate PK value (1.38 +/- 0.05 units/ml; P = NS). Among patients in the microalbuminuric subgroup, we observed a positive and independent correlation between PK and AER in univariate and multivariate regression analysis (r = 0.27, P < 0.03; n = 63). We concluded that in type 1 diabetes, 1) PK levels are elevated in association with increased blood pressure; 2) PK levels are independently correlated with AER and are categorically elevated in patients with macroalbuminuria; and 3) although the positive correlation between PK and AER within the subgroups of patients with microalbuminuria suggest that PK could be a marker for progressive nephropathy, longitudinal studies will be necessary to address this issue.

Occurrence of insect kinins in the flesh fly, stable fly and horn fly-mass spectrometric identification from single nerves and diuretic activity.

MALDI-TOF mass spectrometric analysis of single lateral abdominal nerves (LANs) demonstrate the presence of the insect kinin Musdo-K in the housefly Musca domestica, and identify heretofore unknown insect kinins in two other Dipteran species as Musdo-K in the stable fly Stomoxys calcitrans and horn fly Haematobia irritans. The insect kinin native to the flesh fly Neobellieria bullata is identified as Drome-K. Musdo-K and Drome-K are identical save for the conservative substitution of Ser for Thr in position 2. The sequences of the insect kinins are, therefore, remarkably conserved throughout Dipterans. The in vitro Malpighian tubule fluid secretion activity of Musdo-K in the stable fly is similar to that in the housefly, whereas that of Drome-K is 30-fold more potent in the flesh fly than in the fruit fly. Given the structural identities of the kinins and CRF-like diuretic hormones of these Dipteran species, the housefly can serve as a model insect for the study of diuretic peptides and their functions in the stable fly and horn fly, both livestock pests.

[The assessment of expression of kininogen and bradykinin receptors genes in different vulvar pathologies by QPCR (TaqMan)]. / Ocena ekspresji genów kodujacych kininogen oraz receptory kinin w róznych stanach patologii sromu metoda QPCR (TaqMan).

OBJECTIVES: In different vulvar pathologies inflammatory process and pain are often observed. In these processes, kinins, released from kininogen, play an important role. Their effects are mediated by at least two types of bradykinin receptors--B1 and B2. B1 receptor appears in certain pathological states, B2 is widely distributed in normal tissues. The expression of genes coding kininogen, B1 and B2 receptors can be a very sensitive marker of tissue pathology. DESIGN: In the present study, the analysis of expression of genes coding kininogen, B1 and B2 was performed. The relation between the analysed genes expression and the pathology stage was analysed. MATERIALS AND METHODS: The specimens from condylomata accuminata, vulvar cancer and surgical margin were analysed. The number of DNA and mRNA copies of beta-actine, kininogen, B1 and B2 were examined basing on Q-PCR standard curves for beta-actine by use of Perkin Elmer-kit and the sequence detector ABI PRISM 7700-Taq Man application. RESULTS: In condylomata accuminata the high expression of mRNA of kininogen, B1 and B2 was found, while in vulvar cancer tissue, the expression of analysed genes was low. In the tissue from the tumour center, the lowest kinin genes expression was stated. CONCLUSIONS: The absence of kininogen and B2 mRNA expression characterised vulvar cancer tissue. The profile of expression of kininogen and its receptor genes can be a useful marker in the assessment of vulvar cancer surgical margin.

Towards understanding the kallikrein-kinin system: insights from measurement of kinin peptides.

The kallikrein-kinin system is complex, with several bioactive peptides that are formed in many different compartments. Kinin peptides are implicated in many physiological and pathological processes including the regulation of blood pressure and sodium homeostasis, inflammatory processes, and the cardioprotective effects of preconditioning. We established a methodology for the measurement of individual kinin peptides in order to study the function of the kallikrein-kinin system. The levels of kinin peptides in tissues were higher than in blood, confirming the primary tissue localization of the kallikrein-kinin system. Moreover, the separate measurement of bradykinin and kallidin peptides in man demonstrated the differential regulation of the plasma and tissue kallikrein-kinin systems, respectively. Kinin peptide levels were increased in the heart of rats with myocardial infarction, in tissues of diabetic and spontaneously hypertensive rats, and in urine of patients with interstitial cystitis, suggesting a role for kinin peptides in the pathogenesis of these conditions. By contrast, blood levels of kallidin, but not bradykinin, peptides were suppressed in patients with severe cardiac failure, suggesting that the activity of the tissue kallikrein-kinin system may be suppressed in this condition. Both angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) inhibitors increased bradykinin peptide levels. ACE and NEP inhibitors had different effects on kinin peptide levels in blood, urine, and tissues, which may be accounted for by the differential contributions of ACE and NEP to kinin peptide metabolism in the multiple compartments in which kinin peptide generation occurs. Measurement of the levels of individual kinin peptides has given important information about the operation of the kallikrein-kinin system and its role in physiology and disease states.

Angiotensin-converting enzyme inhibition modifies angiotensin but not kinin peptide levels in human atrial tissue.

Angiotensin-converting enzyme (ACE) converts angiotensin I (Ang I) to angiotensin II (Ang II) and metabolizes bradykinin and kallidin peptides. Decreased Ang II levels and increased kinin peptide levels are implicated in the mediation of the therapeutic effects of ACE inhibition. However, alternative non-ACE pathways of Ang II formation have been proposed to predominate in human heart. We investigated the effects of ACE inhibition on cardiac tissue levels of angiotensin and kinin peptides. High-performance liquid chromatography-based radioimmunoassays were used to measure angiotensin peptides and hydroxylated and nonhydroxylated bradykinin and kallidin peptides in right atrial appendages of subjects who had been prepared for cardiopulmonary bypass. Peptide levels in subjects who received ACE inhibitor therapy were compared with those who did not receive ACE inhibitor therapy. ACE inhibition reduced Ang II levels, which was associated with an 80% reduction in the Ang II/Ang I ratio. ACE inhibition did not modify either bradykinin or kallidin peptide levels or the bradykinin-(1-7)/bradykinin-(1-9) ratio. The 80% reduction in the Ang II/Ang I ratio by ACE inhibition indicated a primary role for ACE in the conversion of Ang I to Ang II in atrial tissue. These data support a role for reduced Ang II levels but do not support a role for increased kinin peptide levels in mediating the direct cardiac effects of ACE inhibition.

Type 2 bradykinin-receptor antagonism does not modify kinin or angiotensin peptide levels.

Type 2 bradykinin (B2)-receptor antagonists have been used to define the role of endogenous kinin peptides. However, interpretation of the effects of B2-receptor antagonists has been limited by lack of information concerning the effects of these antagonists on endogenous kinin and angiotensin peptide levels. If kinin levels were subject to short-loop-feedback regulation mediated through B2 receptors, then a reactive increase in kinin levels might blunt the effects of B2-receptor antagonism and stimulate type 1 bradykinin receptors. Moreover, kinins have been implicated in the control of renin secretion. We investigated whether endogenous kinin levels are subject to short-loop-feedback regulation mediated by the B2 receptor and whether endogenous kinins acting through the B2 receptor influence plasma renin levels and circulating and tissue angiotensin peptide levels. The B2-receptor antagonist icatibant (1 mg/kg) was administered to rats by intraperitoneal injection, and circulating and tissue levels of angiotensin and kinin peptides were measured after 4 hours. Icatibant produced 75% occupancy of B2 receptors in the inner stripe of the renal medulla. Icatibant did not influence plasma levels of renin, angiotensinogen, angiotensin-converting enzyme, neutral endopeptidase, or circulating or tissue levels of angiotensin and bradykinin peptides. This study demonstrated that kinin levels are not subject to short-loop-feedback regulation mediated through B2 receptors and that endogenous kinin levels acting through the B2 receptor do not modulate the renin-angiotensin system.

Salivary gland tissue kallikrein family and processing of growth factor precursors and proenzymes.

Four major enzymes of the tissue kallikrein family were purified from the mouse submandibular gland and characterized. The sequences indicated that they were mK1, mK9, mK13, and mK22. All four enzymes showed kinin-releasing activity, with mK1 exhibiting the highest activity. Like mK13, mK9 and mK22 also processed prorenin to give renin and/or arginyl renin, although their activities were less than that of mK13. The results suggest that tissue kallikrein family enzymes bearing higher kinin-releasing activity have lower prorenin-converting activity and vice versa. These enzymes may possibly have a physiological role in the tissue renin-angiotensin system.

Vespula vulgaris venom: role of kinins and release of 5-hydroxytryptamine from skin mast cells.

Wasp venoms contain several active components, among them kinin-related peptides. Like bradykinin and [Thr6]bradykinin, Vespula vulgaris venom caused paw oedema following subplantar injection in anaesthetized rats. The oedema was partly inhibited by the bradykinin B2 receptor antagonist icatibant (Hoe 140); the remaining part was abolished by additional pretreatment with 5-hydroxytryptamine (5-HT) receptor antagonists or mast cell depletion. Histamine receptor antagonists were ineffective. Capsaicin pretreatment attenuated oedema formation indicating a neurogenic sensory component. Nociceptive behavioural responses induced by the venom in unanaesthetized rats were abolished by icatibant. It is concluded that kinins, either contained in the venom or released from the tissue, play the predominant role in the inflammatory and algesic effects. The inflammatory effects only partly rely on direct, bradykinin receptor-mediated mechanisms while the remaining part depends on the release of 5-HT from skin mast cells. The algesic effects of the venom are entirely due to direct B2 receptor activation.

Left ventricular hypertrophy and its relation to the cardiac kinin-forming system in hypertensive and diabetic rats.

We investigated the cardiac tissue kallikrein and kininogen levels, left ventricular wall thickness and mean arterial blood pressure of Wistar Kyoto and spontaneously hypertensive rats with and without streptozotocin-induced diabetes. The mean arterial blood pressure was highly elevated (P<0.001) in Wistar Kyoto diabetic and spontaneously hypertensive diabetic rats as compared with their respective controls. The cardiac tissue kallikrein and kininogen levels were reduced significantly (P<0.001) in diabetic Wistar Kyoto, spontaneously hypertensive and diabetic spontaneously hypertensive compared with Wistar Kyoto control rats. In addition, the left ventricular thickness was found to be increased (P<0.001) in diabetic Wistar Kyoto and spontaneously hypertensive rats in the presence and in the absence of diabetes. Our results indicate that reduced activity of the kinin-forming system may be responsible for inducing left ventricular hypertrophy in the presence of raised mean arterial blood pressure in diabetic and hypertensive rats. Thus, the kinin-forming components might have a protective role against the development of left ventricular hypertrophy. The possible significance of these findings is discussed.

A double-blind study of the discontinuation of ragweed immunotherapy.

BACKGROUND: Immunotherapy effectively treats the symptoms of allergic rhinitis and improves its pathophysiology. We studied whether the effects of immunotherapy on the early response to nasal challenge with antigen and seasonal symptoms persist after discontinuation. METHODS: Twenty subjects with ragweed allergy who were receiving immunotherapy and who had nasal challenges performed before initiation of treatment were selected. The patients had been receiving maintenance therapy with aqueous ragweed extract at a dose of 12 microg of Amb a 1 equivalent for a minimum of 3 years, at which point they were randomized to receive either placebo injections or to continue with the maintenance dose. Nasal challenges were performed before and 1 year after randomization. Nasal challenges were monitored by counting the number of sneezes and measuring histamine, N-alpha-tosyl-L-arginine methyl ester-esterase activity, and kinins in recovered nasal lavages. In the same year symptom diaries were collected during the ragweed season. RESULTS: The initial immunotherapy significantly reduced responses to nasal challenge in both groups. The group continuing to receive active treatment showed no significant changes from the response before randomization. In contrast, the group randomized to placebo treatment showed a partial return of histamine, kinins, and N-alpha-tosyl-L-arginine methyl ester-esterase in nasal secretions and the numbers of sneezes. IgG antibodies to ragweed declined only in the group switched to placebo treatment. Seasonal rises of IgE antibodies to ragweed did not return during the first season after treatment was stopped. Symptoms reported during the ragweed season were not different between the groups. CONCLUSIONS: One year after discontinuation of ragweed immunotherapy, nasal challenges showed partial recrudescence of mediator responses even though reports during the season appeared to indicate continued suppression of symptoms.

Generation of kinins in synovial fluid from patients with arthropathy.

An enzyme-linked immunosorbent assay method is described for the measurement of kinin formation in synovial fluid from patients with rheumatoid and osteoarthritis (RA and OA). Basal kinin concentrations were less than 6 ng/ml in synovial fluid collected in the presence of inhibitors of kinin forming (kininogenase) and kinin metabolising (kininase) enzymes. During incubation of synovial fluid in the presence of kininase inhibitors alone, kinins were produced rapidly over the first 10 min, but production ceased completely within 30 min due to inhibition of the endogenous kininogenases; the rate of kinin generation during the early rapid phase correlated well with the plateau kinin concentration. Plateau kinin levels in synovial fluid from 15 patients with OA and RA ranged from 98 to 427 ng/ml, with a median value of 148 ng/ml. This study demonstrates clearly that synovial fluid from arthritis patients has the capacity to produce kinins. Although the number of patients was small, the amount of kinin generated in vitro varied over a wide range and a relationship between intra-articular kinin formation and clinical features may become apparent in a larger group of patients. The technique could also be used to investigate other biological systems in which a role has been proposed for kinins.

[Evaluation of bradykinin levels and activation of Tame-esterase in Bronchial alveolar lavage fluid of patients with bronchial asthma]. / Ocena stezenia bradykininy i aktywnosci TAME-esterazy w popluczynach oskrzelowo-pecherzykowych u chorych na astme oskrzelowa.

Airway inflammation is a prominent feature of chronic airway disease as asthma and chronic bronchitis. Multiply cells released mediators and neurotransmitters which are likely to be involved in their origination. The purpose of this study was to establish the levels of kinin, albumin, TAME-esterase activity in BAL fluid of symptomatic and asymptomatic asthmatic patients and to determinate the relationship among mediators. There were significant increases in the mean concentrations of kinin, HSA, TAME-esterase activity in BAL fluid from patients with asthma, chronic bronchitis, compared with the controls (p < 0.005). Kinin mean concentration was in asthmatics 5313, 2 ng/ml, in chronic bronchitis patients 6796.2 ng/ml, versus 468.1 ng/ml in control group. TAME-esterase activity in investigated group was as follow asthmatics 12666 cmp, CB 15131, 3 cmp, versus 3695, 5 cmp in controls. We observed good correlation of kinin and TAME-esterase with HSA in BAL fluid suggest vascular origin of the mediators. The presence of kinins, TAME-esterase in BALs from symptomatic asthmatics and patients with chronic bronchitis provide strong evidence that kinins are involved in this group of lower airway diseases.

Inhibition of angiotensin-converting enzyme--a new concept of medical treatment of male infertility?

OBJECTIVES: To evaluate the effectiveness of systemic captopril therapy. DESIGN: Randomized double-blind study. SETTING: Andrology Unit at the Department of Dermatology, University of Munich, Munich, Germany. PATIENTS: Infertile men suffering from oligozoospermia (5-20 x 10(6) spermatozoa/mL) and/or asthenozoospermia. INTERVENTIONS: Captopril was given orally; samples of seminal plasma were collected twice before treatment and 4 and 12 weeks after captopril administration. MAIN OUTCOME MEASURE: Semen parameters, pregnancy rate, ACE activity, and kinin levels. RESULTS: After 4 weeks of therapy, significant differences between verum group and placebo group were found concerning ACE activity and kinin levels. Sperm density improved significantly after 12 weeks of captopril therapy. All other semen parameters remained unchanged. The pregnancy rate was not improved. CONCLUSIONS: The suitability of captopril in the therapy of oligozoospermia and/or asthenozoospermia for improvement of male infertility seems to be limited.