Cyclic nucleotide-dependent relaxation in human umbilical vessels.

Umbilical vessels have a low sensitivity to dilate, and this property is speculated to have physiological implications. We aimed to investigate the different relaxing responses of human umbilical arteries (HUAs) and veins (HUVs) to agonists acting through the cAMP and cGMP pathways. Vascular rings were suspended in organ baths for isometric force measurement. Following precontraction with the thromboxane prostanoid (TP) receptor agonist U44069, concentration-response curves to the nitric oxide (NO) donor sodium nitroprusside (SNP), the soluble guanylate cyclase (sGC) stimulator BAY 41-2272, the adenylate cyclase (AC) activator forskolin, the ß-adrenergic receptor agonists isoproterenol (ADRB1), salmeterol (ADRB2), and BRL37344 (ADRB3), and the phosphodiesterase (PDE) inhibitors milrinone (PDE3), rolipram (PDE4), and sildenafil (PDE5) were performed. None of the tested drugs induced a relaxation higher than 30% of the U44069-induced tone. Rings from HUAs and HUVs showed a similar relaxation to forskolin, SNP, PDE inhibitors, and ADRB agonists. BAY 41-2272 was significantly more efficient in relaxing veins than arteries. ADRB agonists evoked weak relaxations (< 20%), which were impaired in endothelium-removed vessels or in the presence of the NO synthase inhibitor L-NAME, sGC inhibitor ODQ. PKA and PKG inhibitors impaired ADBR1-mediated relaxation but did not affect ADRB2-mediated relaxation. ADRB3-mediated relaxation was impaired by PKG inhibition in HUAs and by PKA inhibition in HUVs. Although HUA and HUV rings were relaxed by BRL37344, immunohistochemistry and RT-qPCR analysis showed that, compared to ADRB1 and ADRB2, ADRB3 receptors are weakly or not expressed in umbilical vessels. In conclusion, our study confirmed the low relaxing capacity of HUAs and HUVs from term infants. ADRB-induced relaxation is partially mediated by endothelium-derived NO pathway in human umbilical vessels.

The relationship between adiponectin, NT-pro-BNP and left ventricular ejection fraction in non-cachectic patients with systolic heart failure: an observational study.

OBJECTIVE: NT-pro-brain natriuretic peptide (NT-proBNP) has been shown to be an accurate diagnostic marker in patients with heart failure (HF). Adiponectin (Adp) levels are increased in HF but its diagnostic value is still uncertain in these patients. The study was designed to investigate the possible association of these markers in non-cachectic patients with newly diagnosed systolic heart failure. METHODS: Fifty-seven systolic HF patients and 20 matched controls were enrolled in an observational cross-sectional study. Physical and echocardiographic examinations were performed and serum Adp, NT-proBNP, tumor necrosis factor-alpha (TNF-α) levels were measured. Study variables were compared between the groups. Correlation analyses were done and the diagnostic validity of the markers was compared with ROC analysis. RESULTS: Adp and NT-proBNP levels were significantly higher in HF group (20.19±12.9 vs. 7.65±4.6 µg/mL; p<0.001 and 1051.74±606.2 vs. 222.53±65.6 pg/mL; p=0.002; respectively). TNF-α levels were similar between the groups (2.83±1.8 vs. 2.08±1.2 pg/mL; p=0.582). Correlation analysis showed significant association among Adp and NT-proBNP levels, (r=0.448; p<0.001), and left ventricular ejection fraction (LVEF) values (r=-0.466; p<0.001). The Adp and NT-proBNP showed comparable diagnostic performances with mean [95% confidence interval] areas under the curves of 0.857 (0.771-0.944) and 0.888 (0.815-0.960), respectively. CONCLUSION: There were significant correlation between Adp levels with NT-proBNP levels and LVEF values but no any association between Adp levels with body mass index values and TNF-α levels in patients with newly diagnosed systolic heart failure. The result may arouse suspicion about the hypothesis, which proposes that Adp levels simply reflects disease severity or cardiac cachexia in patients with HF.

Acanthamoeba keratitis in a 5-year-old boy without a history of contact lens usage.

PURPOSE: This study was designed to report a case of acanthamoeba keratitis in a 5-year-old child without a history of trauma or contact lens usage. METHODS: The history, clinical presentation, diagnostic, and therapeutic approaches were reviewed. RESULTS: A 5-year-old child without any history of trauma or contact lens use was referred to our university clinic with an initial diagnosis of disciform herpetic keratitis. After 2 weeks of antibacterial and antiviral therapy, a corneal biopsy was performed for diagnostic purposes. The biopsy revealed acanthamoeba. Subsequently intensive therapy with chlorhexidine diacetate 0.02%, ketoconazole tb, hexamidine di-isethionate 0.1% was initiated. At the end of the first month, topical prednisolone acetate 1% was added to reduce inflammation, Chlorhexidine diacetate 0.02% and oral ketoconazole were discontinued, and hexamidine di-isethionate 0.1% was lowered to 4 x 1 and was administered for an additional 4 months. At the end of 5 months, all medications were withdrawn and amblyopia treatment was started. CONCLUSION: When dealing with keratitis in children, acanthamoeba should be considered even without history of contact lens usage or trauma.