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.     

A method for off-line nasal nitric oxide measurement

We conducted a study to test the accuracy of an immediate and delayed off-line technique for measuring nasal nitric oxide (NO) by comparing it with on-line measurements. With the assistance of one volunteer, we obtained these measurements during 30 sessions over a period of 2 months. Off-line measurements were made immediately following the acquisition of NO samples and 1, 2, and 4 hours later. NO samples were obtained from nasal air collected in syringes. We found that the correlation between on-line measurements and the immediate and delayed off-line measurements ranged from 95 to 98%, according to a Bland-Altman analysis. We conclude that off-line nasal NO measurements can be reliably used in clinical practice and research projects, thus obviating the need for patients/subjects to be in close proximity to the analyzer. Off-line nasal NO measurements can effectively substitute for on-line measurements when the latter technique is not practical.     

High output heart failure 8 months after an acquired arteriovenous fistula

Congestive heart failure (CHF) due to hyperkinetic states can occur in systemic diseases and in arteriovenous fistulas. An 18 year old Turkish male patient complaining of dyspnea and palpitations, who had suffered a stab wound to his abdomen eight months earlier, was admitted to our clinic. Auscultation revealed a systolodiastolic murmur over the entire abdomen. Chest x-rays demonstrated significant cardiomegaly. Echocardiography revealed biatrial enlargement and significant mitral and tricuspid regurgitation accompanied by dilatation of the inferior vena cava. Right heart catheterization showed increased oxygen saturation at the inferior vena cava. A diagnosis of an aortocaval fistula was made by aortography. The symptoms subsided and valvular regurgitations ceased alter surgical correction. This rare case demonstrates the significance of routine physical examination and history of the patient.     

The effect of topical fluticasone on nasal nitric oxide levels in a patient with allergic rhinitis

Nitric oxide (NO) in exhaled breath is produced primarily by the upper respiratory airway mucosa. The nasal output of this gas is increased in patients with allergic rhinitis. We performed a study on a 41-year-old nonsmoking male volunteer with allergic rhinitis to investigate the effect of fluticasone nasal spray on nasal NO output (VNO). A total of 28 nasal NO measurements from both nostrils were taken during the 2-month period of June and July 2002. During the second half of the study period (treatment phase), the patient took fluticasone in doses of 100 micrograms per nostril once a day. During the treatment phase, nasal NO measurements were taken 10 days after the initiation of treatment. In addition, we also recorded the patient's nasal symptom scores and the grass pollen counts in the greater Pittsburgh area. The patient's mean VNO was 989.9 nl/min prior to treatment and 787.7 nl/min following treatment--a statistically significant 20.4% decrease (p < 0.01). The findings of our study support the observation that topical nasal steroid treatment decreases NO production in sinonasal mucosa.     

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.     

The endogenous cannabinoid anandamide has effects on motivation and anxiety that are revealed by fatty acid amide hydrolase (FAAH) inhibition

Converging evidence suggests that the endocannabinoid system is an important constituent of neuronal substrates involved in brain reward processes and emotional responses to stress. Here, we evaluated motivational effects of intravenously administered anandamide, an endogenous ligand for cannabinoid CB1-receptors, in Sprague-Dawley rats, using a place-conditioning procedure in which drugs abused by humans generally produce conditioned place preferences (reward). Anandamide (0.03-3 mg/kg intravenous) produced neither conditioned place preferences nor aversions. However, when rats were pre-treated with the fatty acid amide hydrolase (FAAH) inhibitor URB597 (cyclohexyl carbamic acid 3'-carbamoyl-3-yl ester; 0.3 mg/kg intraperitoneal), which blocks anandamide's metabolic degradation, anandamide produced dose-related conditioned place aversions. In contrast, URB597 alone showed no motivational effects. Like URB597 plus anandamide, the synthetic CB1-receptor ligand WIN 55,212-2 (50-300 microg/kg, intravenous) produced dose-related conditioned place aversions. When anxiety-related effects of anandamide and URB597 were evaluated in a light/dark box, both a low anandamide dose (0.3 mg/kg) and URB597 (0.1 and 0.3 mg/kg) produced anxiolytic effects when given alone, but produced anxiogenic effects when combined. A higher dose of anandamide (3 mg/kg) produced anxiogenic effects and depressed locomotor activity when given alone and these effects were potentiated after URB597 treatment. Finally, anxiogenic effects of anandamide plus URB597 and development of place aversions with URB597 plus anandamide were prevented by the CB1-receptor antagonist AM251 (3 mg/kg intraperitoneal). Thus, additive interactions between the effects of anandamide on brain reward processes and on anxiety may account for its aversive effects when intravenously administered during FAAH inhibition with URB597.     

The association between thyroid hormones and arterial stiffness in peritoneal dialysis patients

Background/Aims  

The association between thyroid hormones and arterial stiffness is unclear. In this study, we investigated, for the first time in a large cohort of euthyroid peritoneal dialysis patients, the relationship between thyroid hormone levels and arterial stiffness.