The evaluation of cognitive functions with P300 test for chronic obstructive pulmonary disease patients in attack and stable period

OBJECTIVES: Hypoxia, in chronic obstructive pulmonary disease (COPD), leads to a decrease in cerebral perfusion and an impairment of some cognitive abilities. We aimed to investigate the relation between arterial blood gas analysis (ABA) and pulmonary function test (PFT) parameters with cognitive function of COPD patients during attack and stable period. PATIENTS AND METHODS: ABA, PFT, P300 tests of 30 patients in stabilized period and 30 patients in attack, and 17 healthy controls were evaluated. RESULTS: When both COPD groups and controls were compared, it was seen that latency of P300 was shorter in the control group (p<0.001), but there was no difference between COPD groups (p>0.05). P300 amplitude measures were lower in both COPD groups than control group, but it was not statistically significant (p>0.05). When we compared the measures of attack group, we saw that arterial oxygen tension (PaO(2)), arterial oxygen saturation (SaO(2)), forced expiratory volume in 1s (FEV(1)), FEV(1)/forced vital capacity (FVC) values increased (p<0.001), and P300 latency shortened (p<0.05) in attack group during stable period. P300 latency correlated significantly with PaO(2) (r=-0.557, p<0.001), SaO(2) (r=-0.424, p<0.001), FEV(1) (r=-0.441, p<0.001), FEV(1)/FVC (r=-0.477, p<0.001) values, and age (r=0.329, p<0.05). P300 amplitude is only correlated with PaO(2) (r=0.236, p<0.05). CONCLUSION: Longer latency of P300 appears to be an expected sequel of COPD. P300 test can be considered as a potential objective marker of cognitive impairment.     

Estrogen recruits the endocannabinoid system to modulate emotionality

Estrogen administration elicits anxiolytic and antidepressant-like effects in female rats; however, the mechanism of this effect is unknown. Fatty acid amide hydrolase (FAAH), the enzyme which degrades the endocannabinoid anandamide, has been shown to be regulated by estrogen. Thus, we examined if the anxiolytic and antidepressant effects of estrogen implicated the endocannabinoid system. In the first experiment, ovariectomized female rats were administered a single injection of 17beta-estradiol (10 microg) or oil, and 48 h later were given an injection of the cannabinoid CB1 receptor antagonist AM251 (1 mg/kg) or vehicle. One hour after AM251 or vehicle administration, subjects were tested in either the open field test (OFT), elevated plus maze (EPM) or the forced swim test (FST). Estradiol treatment resulted in a significant increase in open arm entries in the EPM and time spent in the center quadrant of the OFT, which were reversed by co-treatment with AM251, suggesting that endocannabinoids are integral to the anxiolytic effects of estrogen. No significant effects of estradiol or AM251 were seen in the FST. In the second experiment, administration of the FAAH inhibitor URB597 (0.1 and 0.3 mg/kg) increased open arm entries in the EPM and time spent in the center quadrant in the OFT as well as significantly reduced immobility in the FST. Collectively, these data demonstrate that estrogen may elicit changes in emotional behavior through an endocannabinoid mechanism, and suggest that inhibition of FAAH represents a therapeutic target for anxiety and depression in women.     

Attenuation of store-operated Ca2+ current impairs salivary gland fluid secretion in TRPC1(-/-) mice

Agonist-induced Ca(2+) entry via store-operated Ca(2+) (SOC) channels is suggested to regulate a wide variety of cellular functions, including salivary gland fluid secretion. However, the molecular components of these channels and their physiological function(s) are largely unknown. Here we report that attenuation of SOC current underlies salivary gland dysfunction in mice lacking transient receptor potential 1 (TRPC1). Neurotransmitter-regulated salivary gland fluid secretion in TRPC1-deficient TRPC1(-/-) mice was severely decreased (by 70%). Further, agonist- and thapsigargin-stimulated SOC channel activity was significantly reduced in salivary gland acinar cells isolated from TRPC1(-/-) mice. Deletion of TRPC1 also eliminated sustained Ca(2+)-dependent potassium channel activity, which depends on Ca(2+) entry and is required for fluid secretion. Expression of key proteins involved in fluid secretion and Ca(2+) signaling, including STIM1 and other TRPC channels, was not altered. Together, these data demonstrate that reduced SOC entry accounts for the severe loss of salivary gland fluid secretion in TRPC1(-/-) mice. Thus, TRPC1 is a critical component of the SOC channel in salivary gland acinar cells and is essential for neurotransmitter-regulation of fluid secretion.     

Isolated pericardial hydatid cyst in an asymptomatic patient: a remark on its radiologic diagnosis

Cardiac hydatid cyst disease is uncommon, representing approximately 0.2% to 2% of all cyst-related cases. Cardiac hydatid cysts are found mostly within the myocardium. Most cardiac hydatid cysts are located in the interventricular septum or in the left ventricular wall. Only few cases of pericardial location have been reported; isolated pericardial hydatid cysts are especially extremely rare. Patients with a cardiac hydatid cyst are usually asymptomatic. We present the case of an asymptomatic patient with isolated pericardial hydatid cyst disease and discuss the role of chest X-rays in the incidental diagnosis of this condition.     

Simple provocative maneuvers in renal transplant scintigraphy for detecting urine leak

Urine leak in the early postoperative period following renal transplantation is a serious complication requiring early identification and aggressive intervention, which significantly reduces the morbidity and mortality. Renal transplant scintigraphy is a noninvasive method to evaluate the perfusion and function of a transplanted kidney and urinary drainage including urine leak. Here, we reported two cases in which the standard transplant renogram failed to demonstrate urine leak. The cases were referred for a diethylenetriaminepentaacetic acid renogram following the transplantation to evaluate the cause of symptoms or elevated serum creatinine level. In both the cases, urine leak was successfully detected following simple maneuvers such as diuretic administration or Foley catheter irrigation. Renal transplant scintigraphy is an effective and safe technique and the use of these simple maneuvers can enhance the diagnostic sensitivity of the transplant renogram in the detection of urine leak.     

Three-dimensional culture promotes reconstitution of the tumor-specific hypoxic microenvironment under TGFβ stimulation

In vitro tumor growth in a three-dimensional (3D) architecture has been demonstrated to play an important role in biology not only for developmental organogenesis and carcinogenesis, but also for analyses on reconstitution and maintenance in a variety of biological environments surrounding the cells. In addition to providing architectural similarity to living organisms, 3D culture with a radial flow bioreactor (RFB) can also closely mimic the living hypoxic microenvironment under which specific organogenesis or carcinogenesis occurs. The findings of the present study under the RFB culture conditions show that cancer cells underwent a shift from aerobic to hypoxic energy metabolism, in addition to protein expression to maintain the 3D structure. In RFB-cultured cells, protein stability of hypoxia-inducible factor 1 (HIF1) α, a subunit of HIF1, was increased without upregulation of its mRNA. Under these conditions, PHD2, HIF-prolyl-4-hydroxy-lase 2 and a HIF1 downstream enzyme, were stabilized without affecting the mRNA levels via downregulation of FK506-binding protein 8. PHD2 accumulation, which occurred concomitant with HIF1 stabilization, may have compensated for the lack of oxygen under hypoxic conditions to regulate the HIF levels. 3D-culture-induced overexpression of carbonic anhydrase (another representative HIF downstream enzyme) was found to occur independently of cell density in RFB--cultured cells, suggesting that the RFB provided an adequately hypoxic microenvironment for the cultured cells. From these results, it was hypothesized that the key factors are regulatory molecules, which stabilize and degrade HIF molecules, thereby activating the HIF1 pathway under a hypoxic milieu.     

Biglycan protects cardiomyocytes against hypoxia/reoxygenation injury: Role of nitric oxide

Biglycan, a proteoglycan component of extracellular matrix, has been suspected to contribute to the development of atherosclerosis, but overexpression of biglycan in transgenic mice has been shown to induce cardioprotective genes including nitric oxide (NO) synthases in the heart. Therefore, here we hypothesized if exogenous administration of biglycan exerts cytoprotection. Primary cardiomyocytes from neonatal rats were subjected to 150 min hypoxia and 2 h reoxygenation. Mortality of cardiomyocytes was dose-dependently attenuated by pretreatment with 1-100 nM biglycan. Biglycan enhanced eNOS mRNA and protein, and significantly increased NO content of cardiomyocytes. The NO synthase inhibitor l-nitro-arginine-methyl-ester significantly attenuated the cytoprotective effect of biglycan. This is the first demonstration that biglycan leads to cytoprotection against hypoxia/reoxygenation injury, and that this phenomenon is partially mediated by an NO-dependent mechanism.     

Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis

Reduced functional bladder capacity and concomitant increased micturition frequency (pollakisuria) are common lower urinary tract symptoms associated with conditions such as cystitis, prostatic hyperplasia, neurological disease, and overactive bladder syndrome. These symptoms can profoundly affect the quality of life of afflicted individuals, but available pharmacological treatments are often unsatisfactory. Recent work has demonstrated that the cation channel TRPV4 is highly expressed in urothelial cells and plays a role in sensing the normal filling state of the bladder. In this article, we show that the development of cystitis-induced bladder dysfunction is strongly impaired in Trpv4(-/-) mice. Moreover, we describe HC-067047, a previously uncharacterized, potent, and selective TRPV4 antagonist that increases functional bladder capacity and reduces micturition frequency in WT mice and rats with cystitis. HC-067047 did not affect bladder function in Trpv4(-/-) mice, demonstrating that its in vivo effects are on target. These results indicate that TRPV4 antagonists may provide a promising means of treating bladder dysfunction.     

Health impact assessment of particulate pollution in Tallinn using fine spatial resolution and modeling techniques

Background  

Health impact assessments (HIA) use information on exposure, baseline mortality/morbidity and exposure-response functions from epidemiological studies in order to quantify the health impacts of existing situations and/or alternative scenarios. The aim of this study was to improve HIA methods for air pollution studies in situations where exposures can be estimated using GIS with high spatial resolution and dispersion modeling approaches.