Protective effect of quercetin,a polyphenolic compound,on mouse corpus cavernosum

Flavonoids are plant‐based phenolic compounds, and quercetin is the most abundant dietary member of this family. One of the most important characteristics of quercetin is its antioxidant property. The aim of this study was to investigate antioxidant effects of quercetin on corpora cavernosa of mice. Corpora cavernosa were isolated in organ baths, precontracted with phenylephrine (0.5 μm ) and relaxant responses were mediated by acetylcholine (0.1–1 μm ), electrical field stimulation (EFS, 1–16 Hz, 0.5 ms, 30 V) or acidified sodium nitrite (a NaNO₂, 0.5 mm ). Superoxide anion generators; pyrogallol (50 μm ), hydroquinone (100 μm ), LY 83583 (6‐Anilinoquinolin‐5,8‐quinone, 10 μm ) and superoxide dismutase (SOD) inhibitor; diethyldithiocarbamic acid (DETCA, 8 mm ) were used in order to expose corpus cavernosa to oxidant stress. Acetylcholine (0.1–1 μm ) induced relaxant responses were significantly inhibited in LY 83583 (10 μm ) and DETCA + LY 83583 applicated trials. EFS‐induced relaxant responses were significantly inhibited in DETCA (8 mm ) and DETCA + LY 83583 administrated trials. On the other hand, acidified sodium nitrite‐induced responses were inhibited by all of the superoxide anion generators tested. Quercetin (10 μm ) failed to improve the inhibitions on endothelium and electrically stimulated responses. Acidified sodium nitrite (0.5 mm ) mediated relaxant responses were significantly restored by quercetin except the groups in which LY 83583 were used. The data suggest that quercetin acts as a protective agent in mouse corpus cavernosum, increasing the bioavailability of exogenous nitric oxide by protecting it from superoxide anion (O₂^–).     

Leptospiral Outer Membrane Protein LipL41 Is Not Essential for Acute Leptospirosis but Requires a Small Chaperone Protein,Lep, for Stable Expression

Leptospirosis is a worldwide zoonosis caused by pathogenic Leptospira spp., but knowledge of leptospiral pathogenesis remains limited. However, the development of mutagenesis systems has allowed the investigation of putative virulence factors and their involvement in leptospirosis. LipL41 is the third most abundant lipoprotein found in the outer membranes of pathogenic leptospires and has been considered a putative virulence factor. LipL41 is encoded on the large chromosome 28 bp upstream of a small open reading frame encoding a hypothetical protein of unknown function. This gene was named lep, for LipL41 expression partner. In this study, lipL41 was found to be cotranscribed with lep. Two transposon mutants were characterized: a lipL41 mutant and a lep mutant. In the lep mutant, LipL41 protein levels were reduced by approximately 90%. Lep was shown through cross-linking and coexpression experiments to bind to LipL41. Lep is proposed to be a molecular chaperone essential for the stable expression of LipL41. The roles of LipL41 and Lep in the pathogenesis of Leptospira interrogans were investigated; surprisingly, neither of these two unique proteins was essential for acute leptospirosis.     

Risk factors of abuse of parents by their ADHD children

It is interesting that there is scant research of abuse of parents by their children and no study was found on the abuse of parents by their attention deficit hyperactivity disorder (ADHD) children. Seventy-four children and adolescents suffering from ADHD and their parents were interviewed. The diagnoses were made according to DSM-IV diagnostic criteria. A questionnaire was developed to assess the children’s abuse toward parents. More than half of the parents are suffering from at least one of the forms of abuse by their ADHD children. Scores of parental abuse were not related to gender. Different types of abuse correlated with oppositional defiant disorder (ODD), tic, and separation anxiety disorder (SAD). Fathers’ and mothers’ age, the level of education, and type of occupation were not risk factors of the abuse scores. ODD and mother’s major depressive disorder were predictors of the abuse. There was a very disturbing high rate of abuse by children against parents. There is an interrelation of different forms of abuse. This study contributes to increasing awareness on the abuse of parents by their ADHD children.     

Pharmacological treatment of high‐normal blood pressure (prehypertension) in high‐risk patients for primary prevention of cardiovascular events

Currently, the best treatment strategy for patients with a high‐normal blood pressure (prehypertension) is not known. The authors aimed to determine whether pharmacological reduction of systolic blood pressure (SBP) to a normal level (<120 mm Hg) would prevent cardiac morbidity and mortality in prehypertensive patients. In this secondary analysis, the authors obtained the data from SPRINT from the National Heart, Lung, and Blood Institute data repository center. Among 9361 patients enrolled in SPRINT, 289 high‐risk (ASCVD risk = 24.8% ± 13.0 [10‐65]) prehypertensive patients without previous cardiovascular disease and not receiving any antihypertensive medications were enrolled. One hundred and forty‐eight of them were assigned to standard treatment which consisted of clinical follow‐up till SBP goes above 140 mm Hg and then staring medications to keep SBP <140 mm Hg. One hundred and forty‐one were assigned to the intensive treatment receiving pharmacological SBP reduction to <120 mm Hg upon enrollment. The primary composite outcome was myocardial infarction, and other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. Throughout the 3.06 years of follow‐up, a primary outcome event was confirmed in three participants (0.74% per year) in the intensive‐treatment group and 8 (1.61% per year) in the standard‐treatment group (hazard ratio [HR], 0.19; P = .045). Rates of serious adverse events were not increased by intensive‐treatment (HR, 0.83; P = .506). Based on this secondary post hoc analysis, intensive SBP reduction may probably be beneficial for primary prevention of cardiovascular morbidity and mortality in high‐risk prehypertensive patients. This finding needs to be evaluated in a larger trial designed specifically to answer this question.     

Intraocular lysozyme in experimental uveitis in rabbits: aqueous and vitreous assay.

We determined normal aqueous and vitreous lysozyme levels in rabbit eyes and induced experimental uveitis to record the uppermost aqueous and vitreous lysozyme levels. The normal aqueous humor of the rabbit eye contained 1.05 mug per milliliter lysozyme and the normal vitreous humor contained 0.45 mug per milliliter. After the intravitreal administration of a foreign protein, the aqueous and vitreous lysozyme levels rose within one day, reaching maximum values of 38.4 mug per milliliter and 114 mug per milliliter, respectively, at 14 days, and subsequently declining to minimal values by 28 days after injection.     

Risk factors for clinically significant macular edema in a multi-ethnics population with type 2 diabetes

AIM: To determine the risk factors of clinically significant macular edema (CSME) in patients with non-proliferative diabetic retinopathy (NPDR) in a multi-ethnics Malaysian population. METHODS: We performed a case control study in which 150 patients with bilateral NPDR and CSME in either eye were compared to 150 patients with bilateral NPDR and no CSME in both eyes. CSME and NPDR were graded according to Early Treatment of Diabetic Retinopathy Study criteria. Student’s t-test, odds ratio and multiple logistic regression analysis were performed to analyze the duration of diabetes, body mass index (BMI), blood pressure(BP), total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides (TG), fasting blood glucose (FBG), HbA1c, full blood count, serum creatinine and proteinuria between the two groups. RESULTS: Both groups were matched in terms of age, gender and ethnicity. Duration of diabetes, total serum cholesterol, serum LDL, FBG, HbA1c and serum creatinine were significantly higher in the CSME group (P<0.05). The hemoglobin, packed cell volume were significantly lower in the CSME group (p<0.05). There was no significant difference for serum HDL, TG, BMI, systolic and diastolic BP. Multiple logistic regression analysis showed that total serum cholesterol and HbA1c had significantly high odds of developing CSME. CONCLUSION: HbA1c and total cholesterol are the two most important risk factors associated with CSME in patients with NPDR.     

Intraocular acyclovir levels after subconjunctival and topical administration.

Substantial levels of acyclovir were detected in the aqueous and vitreous of New Zealand rabbits at various time intervals following subconjunctival injection. Intravitreal penetration of acyclovir after topical application was poor.     

Intravitreal penetration of oral pefloxacin in humans

We measured vitreous and serum levels of pefloxacin after oral administration. Twenty patients with retinal detachments undergoing vitrectomy were recruited into this study. Each patient received 400 mg pefloxacin orally 1 to 12 hours before vitrectomy. Vitreous fluid (0.1 mL) was aspirated at surgery. Vitreous levels of pefloxacin were determined by high-performance liquid chromatography. Six hours after oral administration, an average level of 1.37 g/mL of pefloxacin was measured in the vitreous samples. These levels were well above the minimum inhibitory concentration (MIC) for most organisms termed sensitive to pefloxacin. Oral administration of pefloxacin may play an important role in the prevention or management of endophthalmitis.Supported in part by U.S. Public Health Service grants EY07541 and EY02377 from the National Eye Institute, National Institutes of Health, Bethesda, MD, USA.     

Collagen shields and intraocular drug delivery: concentration of gentamicin in the aqueous and vitreous of a rabbit eye after lensectomy and vitrectomy

Five albino New Zealand rabbits underwent bilateral lensectomy and vitrectomy. All left eyes were fitted with a collagen shield that had been soaked for 5 min in 2.0 mL of gentamicin solution (40 mg/mL for IV use). Right eyes were treated with fortified gentamicin drops (13.6 mg/mL) every 30 min for 12 hrs. Aqueous and vitreous specimens were obtained at the following time intervals: 1, 2, 4, 8, 12 and 24 hrs.We found the gentamicin concentrations to be higher in the aqueous of all eyes treated with fortified gentamicin drops. Only those eyes treated with fortified gentamicin drops attained a therapeutic drug level (4g–9g/mL) in the aqueous. Therapeutic drug levels were not attained in the vitreous of either treatment group.     

Effect of squalamine on iris neovascularization in monkeys

PURPOSE: To investigate the effect of squalamine, an antiangiogenic aminosterol, in an experimental model of iris neovascularization. METHODS: Iris neovascularization was created in cynomolgus monkeys by occluding retinal veins with an argon laser and inducing persistent hypotony with a central corneal suture. Twenty-four eyes were treated in three groups. In Group 1, four eyes were injected intravitreally with 3 microg/0.1 mL squalamine and four eyes with balanced saline solution (controls) immediately after vein occlusion (day 1); injections were repeated every 3 days for 3 weeks. In Group 2, 1 mg/kg squalamine was administered with intravenous infusion in dextrose 5% in four animals; four control animals received only dextrose. Infusions began on day 1 and were repeated every 3 days for 3 weeks. In Group 3, after development of iris neovascularization on day 7, 1 mg/kg squalamine was injected systemically in four animals; four control animals received dextrose 5%. Monkeys were examined by slit-lamp biomicroscopy and underwent color photography and fluorescein angiography. RESULTS: Group 1: All eyes, treated and control, developed intense and persistent rubeosis iridis. Group 2: Two of the four treated eyes in this group developed minimal iris neovascularization; the other two had no iris neovascularization. All four control eyes developed intense, persistent iris neovascularization. Group 3: All eyes developed extensive rubeosis iridis; iris neovascularization regressed in all four treated eyes after squalamine injections. Two of four treated eyes retained minimal iris neovascularization; two showed complete regression of rubeosis iridis. Rubeosis iridis completely regressed in two of the four control eyes; the remaining two control eyes had intense, persistent iris neovascularization. CONCLUSIONS: Intravitreally injected squalamine did not affect the development of iris neovascularization; however, systemic squalamine injection inhibited the development of iris neovascularization and caused partial regression of new vessels in a primate model.