Detection of angiotensin II in supernatants of stimulated mononuclear leukocytes by matrix-assisted laser desorption ionization time-of-flight/time-of-flight mass analysis

Angiotensin II (Ang II) is the major vasoactive component of the renin-angiotensin system. Several components of the renin-angiotensin system have been demonstrated in different tissues. Whereas the roles of tissue and renal renin-angiotensin system have been studied in detail, much less is known on whether the corpuscular elements of circulating blood contribute to Ang II production. Here we examined whether, in addition to vasculature, blood cells also contribute to the circulating Ang II levels. Mononuclear leukocytes were obtained from healthy subjects and were incubated. The resulting supernatant was chromatographed using different chromatographic methods. The vasoconstrictive effects of aliquots of the resulting fractions were tested. Each fraction with a vasoconstrictive effect was analyzed by mass spectrometry. In one fraction with a strong vasoconstrictive effect, Ang II was identified. Mononuclear lymphocytes produced Ang II in amounts sufficient to stimulate Ang II type 1 receptors. Moreover, in mononuclear leukocytes, renin as well as angiotensin-converting enzyme mRNA expression was detectable by RT-PCR. These findings demonstrate that mononuclear leukocytes are a source of Ang II. Ang II secretion by these cells may play a significant role in humoral vascular regulation. In conclusion, the isolation of Ang II in supernatants of mononuclear leukocytes adds a further physiological source of Ang II to the current view of angiotensin metabolism. The quantitative role of lymphocyte-derived Ang II secretion compared with the other sources of Ang II should be defined further, but the release found under the present conditions is at least sufficient to elicit vasoconstrictive effects.     

An infant with pentalogy of Cantrell and limb defects diagnosed prenatally

We present a case of pentalogy of Cantrell which was diagnosed prenatally on routine ultrasound examination. There were several associated limb defects. We discuss the differential diagnosis and conclude that our case probably had a variant form of this syndrome.     

Occupational asthma, eosinophil and skin prick tests and serum total IgE values of the workers in a plant manufacturing rose oil

This study was aimed to determine the rate of occupational asthma (OA) in workers at a rose extracting plant. Specific clinical tests of 52 workers, randomly chosen from four local rose extracting plants, were statistically compared with the test results of 30 local control subjects of similar age and sex as the plant workers, but who had never worked in such a plant. There were no significant differences in pulmonary function tests (FVC, FEV1, FEV1/FVC, PEFR) between the control and test groups. Significantly higher serum total IgE values (p < 0.0001) were observed for the test subjects (239.08+/-240 IU/ml) compared to the control subjects (81.33+/-61.45 IU/ml). There were also significant differences (p < 0.0001) in the number of eosinophils between the control and test groups, with corresponding mean values of 2.28+/-2.75% and 0.73+/-1.72%, respectively. A specifically prepared skin prick test using a rose allergen (Rosa domescena) was positive for 53.84% in the test subjects whereas only 5.33% positive test results were seen in the control group. We have demonstrated the involvement of Rosa domescena pollen in occupational allergy, through IgE-mediated hypersensitivity. It was concluded that the workers of a rose oil extracting plant are more susceptible to the rose pollens.     

Electron spin resonance spectroscopy reveals alpha-phenyl-N-tert-butylnitrone spin-traps free radicals in rat striatum and prevents haloperidol-induced vacuous chewing movements in the rat model of human tardive dyskinesia

The typical antipsychotic drug haloperidol causes vacuous chewing movements (VCM) in rats, which are representative of early-Parkinsonian symptoms or later-onset extrapyramidal side effects of tardive dyskinesia (TD) in humans. Haloperidol (HP) has been hypothesized to potentiate increases in oxidative stress or free radical-mediated levels of toxic metabolites in rat striatum while simultaneous upregulating dopamine (DA)-D2 receptors leading to presumed DA supersensitivity. Alpha(alpha)-Phenyl-N-tert-butylnitrone (PBN) is an antioxidant used to combat oxidative stress and measure increases in PBN spin-adduct activity. Thus, the aim of this study was to investigate whether VCMs are related to upregulation of DA-D2 receptors or to increased levels of free radicals produced during oxidative stress, and whether PBN had any protective effects. Rats received daily chronic (28 day) i.p. injections of saline, haloperidol (2 mg/kg), PBN (150 mg/kg), or haloperidol + PBN. The VCM model was used to measure extrapyramidal side effects of drug treatments. Electron spin resonance (ESR) spectroscopy was performed to compare concentrations of free radical species in rats receiving injections of HP + PBN. To examine the upregulation of DA-D2 receptors, binding assays were carried out to assess the increase in DA-D(2) receptor numbers with respect to VCMs following treatment of rats injected with HP, PBN, and HP + PBN. Results of these experiments show that HP-induced VCMs in rats results from increases in oxidative cellular events and may not be related to increases in striatal DA-D(2) receptors.     

Percutaneous mitral balloon valvuloplasty in rheumatic mitral stenosis without heparin

BACKGROUND AND AIM OF THE STUDY: Customarily, heparin is used to prevent embolic complications arising during percutaneous mitral balloon valvuloplasty (PMBV), but this may prolong hospital stay and increases the risk of bleeding, hemopericardium and cardiac tamponade. The study aim was to assess in-hospital complications of PMBV performed without heparin. METHODS: Rheumatic mitral stenosis patients undergoing PMBV between February 1997 and March 2000, either with (18 males, 91 females; mean age 37.5 +/- 8.8 years) or without (15 males, 119 females; mean age 37.5 +/- 15.1 years) heparin at conventional doses, were included in the study. Neurologic and cardiac examinations were conducted after PMBV and repeated before discharge from hospital. RESULTS: There was no statistically significant difference between groups in terms of age, gender, NYHA class, presence of atrial fibrillation, spontaneous echo contrast, left atrial appendix thrombus, left atrial diameter and mitral valve echo score. There was no difference between groups with regard to procedural success, mitral valve area and gradient attained, or rates of mitral insufficiency. Ten patients in the heparin group required transesophageal echocardiography (TEE) guidance during PMBV (p <0.001). The mean duration of PMBV was greater in the heparin group due to increased use of TEE guidance during septal puncture. During follow up, no patients in the non-heparin group had hemopericardium, cardiac tamponade, embolic event or death; by comparison, in the heparin group one patient had hemopericardium and one had a cardiac tamponade. No major bleeding episode requiring transfusion occurred in either group, but six and 10 cases of minor bleeding at access sites occurred in the non-heparin and heparin groups, respectively (p = NS). Duration of hospitalization was statistically longer in the heparin group than in the non-heparin group. CONCLUSION: Avoidance of heparin did not lead to an increase in embolic complications. The vascular access sites were withdrawn early, thereby reducing the duration of hospital stay and time to ambulation. This method did not cause any increase in numbers of vascular complications and blood transfusions.     

Evaluation of the novel antiepileptic drug,AWD 131-138, for benzodiazepine-like discriminative stimulus and reinforcing effects in squirrel monkeys

AWD 131-138 [1-(4-chlorophenyl)-4-morpholino-imidazolin-2-one], a new low-affinity partial benzodiazepine receptor agonist with potent anticonvulsant and anxiolytic properties in rodent models, was studied in squirrel monkeys trained to discriminate intramuscular (i.m.) injections of midazolam (0.3 mg/kg) from injections of vehicle. Diazepam produced midazolam-like responding at cumulative doses of 1.0 and 3.0 mg/kg i.m. and decreased rates of responding at 3.0 mg/kg (plasma levels of about 400 ng/ml). In contrast, AWD 131-138 did not produce midazolam-like responding or alter response rates at cumulative doses up to 18.0 mg/kg i.m. (plasma levels over 2100 ng/ml). Other monkeys were trained to intravenously (i.v.) self-administer cocaine (56.0 microg/kg/injection). When AWD 131-138 (10-100 microg/kg/injection) was studied by substitution, responding declined to vehicle substitution levels within three sessions. At the dose of 100 microg/kg i.v. AWD 131-138, sufficient drug was self-administered during the first session (about 3.5 mg/kg) to produce plasma levels above 1000 ng/ml, yet responding over the next two sessions dropped to vehicle levels. The failure of AWD 131-138 to produce benzodiazepine-like discriminative effects and the absence of drug self-administration behavior when substituted for cocaine suggest that its abuse liability is low.     

Angiotensin converting enzyme gene polymorphism and development of post-transplant erythrocytosis

BACKGROUND: An increased activation of the renin-angiotensin system probably plays a major role in the development of post-transplant erythrocytosis (PTE). It is known that deletion type polymorphism (DD) in the angiotensin converting enzyme (ACE) gene is associated with higher circulating angiotensin II (AII) levels. The aim of this study was to investigate the effect of ACE gene polymorphism on development of PTE. METHODS: 86 PTE patients (male/female: 68/18, mean age: 32 +/- 10 years) and 68 consecutively transplanted non- PTE patients (male/female: 38/30, mean age: 31 +/- 10 years) were included; 140 patients (91%) had been transplanted from living donors; 92 patients (60%) had hypertension. ACE gene polymorphism was determined by polymerase chain reaction (PCR). RESULTS: The mean time to appearance of PTE was 8.8 +/- 7.9 (range of 1-53) months. DD genotype was detected in 65 patients. PTE patients had a higher prevalence of hypertension (70% vs. 46%, p=0.003) and a lower frequency of DD genotype (34% vs. 54%, p=0.014) as compared to non-PTE patients [OR: 2.2 (1.14-4.25, 95% CI)]. PTE developed more frequently in male patients (68/106: 64%) than females (18/48: 38%) (p=0.002). Patients with DD genotype had a significantly longer leading time to PTE in Kaplan-Meier survival analysis with log-rank (136 +/- 15 vs. 92 +/- 13 months, p=0.015). In Cox regression analysis, hypertension (p=0.002) and recipient ACE genotype (p=0.013) were retained as independent variables for predicting PTE development. CONCLUSIONS: PTE develops more frequently in male, hypertensive renal transplant recipients with good allograft function. DD-type ACE gene polymorphism seems to protect against PTE development.     

Plasmacytoma of the temporal bone: management with a combination of surgery and radiotherapy

The diagnosis of solitary plasma cell neoplasm is based on clinical, radiological and laboratory findings and it can be accepted as the precursor lesion of multiple myeloma as spread of disease occurs in 30-50% of affected patients. However, solitary plasmacytoma of the temporal bone is a rare pathology. We present an interesting case of plasmacytoma of the temporal bone which was controlled by a combination of surgery and radiotherapy.     

Sjögren syndrome in ORL. Diagnostic considerations

A presentation the history of a 51-year-old woman with xerostomia and keratoconjunctivitis sicca (KCS), developed in 10 months, investigations revealed the presence in serum of antibodies against cytoplasmic antigens SS-A (Ac anti-Ro/SS-A), antinuclear antibodies (ANAs) and rheumatoid factor (RF). The Rose Bengal test was positive and in the salivary gammagraphy, made with pertecnate 99 mTc, it was observed a decrease of the captation and excretion of the designer for salivary glands. The histopathology and immunohistochemical study of minor salivary glands showed the presence of a focal lymphocitic sialadenitis (fsa) and a predominance of lymphocites CD4+. It was diagnosed as primary Sj?gren's syndrome (PSS) and the patient treated with salivary substitutes, artificial tears and corticoids. We analyse the current diagnostic criteria of the group of study of the European Community for the Sj?gren's syndrome (SS) and emphasize the importance of histologic and immunochemical studies, that together with the rest of complementary tests will led us to distinguish not only the different forms of the presentation of the illness but also those of all patients with pathologies which are nowadays very prevalent in our environment, such as the hepatitis C (HCV) an the human immune deficiency (HIV) virus infections.     

Comparison of the effects of enalapril and losartan on posttransplantation erythrocytosis in renal transplant recipients: prospective randomized study

BACKGROUND: The aim of this prospective randomized study was to compare the safety and efficacy of enalapril (E) and losartan (L) in the treatment of posttransplantation erythrocytosis and the effect of the ACE genotype on response to therapy. METHODS: Twenty-seven (24 male and 3 female, mean age 34+/-8 years) renal transplant recipients with erythrocytosis were treated either with E (15 patients) (10 mg/day) or L (12 patients) (50 mg/day) for 8 weeks. RESULTS: The hemoglobin levels were significantly decreased in the L (17.1+/-0.7 to 15.9+/-1.3 g/dl, P=0.01) and E groups (17.4+/-1.1 to 14.9+/-2.2 g/dl, P=0.001). Among the responders who discontinued treatment, there was a trend for longer time to relapse in the L group (7.38+/-3.75 months; 95% confidence interval: 0.03-14.7) compared with the E group (2.75+/-0.70 (95% confidence interval: 1.37-4.13) (P=0.11). Decrease in hemoglobin was more prominent with E compared with L (-3.26+/-0.65 vs. -1.70+/-0.39 g/dl, P=0.05). Decrease in hemoglobin levels between DD and non-DD genotype groups was similar (-2.0+/-1.5 vs. -1.7+/-2.3 g/dl, P=0.69). CONCLUSIONS: Enalapril caused a greater decrease but faster relapse in hemoglobin levels compared with losartan in patients with posttransplantation erythrocytosis. The DD type polymorphism had no effect on response.