The aim of this study was to determine the effects of endogenous nitric oxide (NO) on cerebral blood flow (CBF) and cerebrovascular resistance (CVR) under conditions of normoxia and hypoxia. Experiments were performed on anesthetized, mechanically ventilated Wistar rats. CBF was measured using the intracarotid 133Xe injection technique. NO formation was inhibited by NG-monomethyl-L-arginine (L-NMMA). Administration of L-NMMA (100 mg kg-1 i.v.) during normoxia resulted in an increase in mean arterial blood pressure from 113 +/- 4 to 145 +/- 4 mm Hg (p less than 0.001), a decrease in CBF of 21% (from 91 +/- 4 to 75 +/- 5 ml 100 g-1 min-1, p less than 0.001), and an increase in CVR of 53% (from 1.3 +/- 0.1 to 2.0 +/- 0.2 mm Hg ml-1 100 g min, p less than 0.001). These effects were reversed by i.v. administration of 300 mg kg-1 of L-arginine but not D-arginine. Moreover, the administration of L-NMMA abolished the enhancement of CBF and the diminution in CVR observed during intracarotid infusion of acetylcholine (ACh). The increase in CBF and decrease in CVR during hypoxia in the group of rats that received L-NMMA were similar to that in the control group, although CBF and CVR levels attained during hypoxia in both groups were different. The results show that NO is involved in the maintenance of basal CBF and CVR, and is responsible for the ACh-elicited increase in CBF and the decrease in CVR in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

IntroductionTwo human-specific Demodex species have been described: Demodex folliculorum and Demodex brevis. A medical condition caused by the presence of Demodex is called demodicosis.Material and methodsThe study material comprised eyelashes collected from 1499 patients.Results Demodex sp. infection was revealed in 47% of patients (487 women and 216 men). We determined the following rates of infection by age groups: 1–25 (8% of infected subjects), 26–40 (36%), 41–55 (50%), 56–70 (67%), over 70 (77%). The sex of the subjects was not identified as a factor conducive to infection (p = 0.108), while their age was positively correlated with the risk of infection (p < 0.005). The 1499 study subjects included patients with blepharitis, rosacea, and rheumatoid arthritis. The study investigated the extent to which the above-mentioned conditions affect the risk of Demodex infection. Applying the method of logistic regression, the infection probability was estimated, depending on the age, sex, and comorbidities such as blepharitis, rosacea, and rheumatoid arthritis. Patients suffering from blepharitis were found to have a nearly 2.5-fold higher risk of Demodex infection than those without blepharitis, and the risk for rosacea patients was determined as three-fold higher than that of the general population.ConclusionsBlepharitis and rosacea are risk factors for Demodex infection.

The purpose of this study was to determine subjective ocular symptoms occurring in patients infested with Demodex. The number of Demodex mites in the obtained material that correlated with the appearance of ocular symptoms was estimated. The study material were eyelashes collected from 1499 patients. The material were observed under a light microscope. T-test, the logistic regression method, and Pearson correlation coefficient were used for the analysis. Demodex mites were detected in 47% patients. The mean ages of infected women and men were 64 and 59 years, respectively. 64% infected patients complained of one or more ophthalmological symptoms. The most commonly reported symptoms included itching (28%), redness of eyelids (21%), and watery eyes (15%). Positive correlation was found between itching, redness, pain, purulence or eyelash loss and the presence of Demodex. The mentioned symptoms increase the probability of Demodex infestation in a statistically significant manner (p<0.005). A correlation between the age and gender and the number of Demodex was revealed by the study. The threshold average number of seven Demodex mites per eight collected eyelashes with which the risk of the occurrence of an ocular symptom increases significantly was defined. In patients with a low number of Demodex mites, symptoms may be absent. The risk of the occurrence of ocular symptom in patients with demodicosis increases with the increase in the average number of Demodex mites.

Previous studies have demonstrated that in adult rats with chronic hyponatremia, both symptoms of encephalopathy and mortality largely depend upon the gender of the animal and the presence of elevated plasma levels of vasopressin (AVP). Since effects of AVP on blood vessels may be gender dependent, the present study was designed to compare the effects of chronic (4 days) hyponatremia on cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2), and cerebral perfusion index (CPI) in adult male and female rats. CBF (intra-arterial 133Xe injection method) and CMRO2 (arteriovenous difference of cerebral oxygen contentxCBF) were measured in normonatremic and hyponatremic (hyponatremia induced with 140 mmol/L glucose and either AVP or desmopressin [dDAVP], plasma sodium = 100 to 110 mmol/L) adult rats of both genders. The CPI was assessed from magnetic resonance imaging of the transit of magnetic susceptibility contrast agent through the brain. Female rats with AVP-induced chronic hyponatremia had a 36% decrease in CBF and a 60% decrease in CMRO2. In male animals, both parameters were not different from control values. AVP-induced hyponatremia resulted in a 45% decrease in CPI in female rats, but hyponatremia induced with dDAVP did not affect CPI in either male or female rats. Chronic (4 days) administration of AVP did not affect CPI in either male or female normonatremic rats. When rats with AVP-induced chronic hyponatremia were pretreated with estrogen, the CPI in males was not different from that in females. Our results demonstrate that during AVP-induced chronic hyponatremia in female rats, there is significant depression of both oxygen utilization and blood flow in the brain.

Pathological angiogenesis is correlated with many ophthalmic diseases. The most common are exudative age-related macular degeneration and proliferative diabetic retinopathy. The current treatment for these diseases is based on regularly administered anti-VEGF antibodies injections. In the study, we investigated selected D2 dopaminergic receptor agonists, namely bromocriptine, cabergoline and pergolide, on hypoxia-induced neovascularization. We used the zebrafish laboratory model, specifically three-day post fertilization (dpf) Tg(fli-1: EGFP) zebrafish larvae. To induce abnormal angiogenesis of hyaloid-retinal vessels (HRVs) and intersegmental vessels (ISVs), the larvae were treated with cobalt chloride (II) (CoCl2) (a hypoxia-inducing agent) from 24 h post fertilization. The inhibitory role of D2 dopaminergic receptor agonists was investigated using confocal microscopy and qPCR. Additionally, the results were compared to those obtained in the group treated with CoCl2 followed by bevacizumab, the well-known antiangiogenic agent. Confocal microscopy analyses revealed severe deformation of vessels in the CoCl2 treated group, while co-incubation with bromocriptine, cabergoline, pergolide and bevacizumab, respectively, significantly inhibited abnormalities of angiogenesis. The qPCR analyses supported the protective role of the chosen dopaminergic agonists by demonstrating their influence on CoCl2-derived upregulation of vegfaa expression. The present results suggest that the D2 receptor agonists can be considered as a new direction in research for antiangiogenic therapy.