Ascorbic acid concentration is reduced in the secondary aqueous humour of glaucomatous patients

P>Background: We aimed to evaluate the ascorbic acid concentration in secondary aqueous humour (AH) from glaucomatous patients and to compare it with primary AH from primary open-angle glaucoma patients and non-glaucomatous patients. Methods: Primary AH samples were prospectively obtained from clinically uncontrolled primary open-angle glaucoma patients and senile cataract patients (controls) prior to trabeculectomy and cataract surgery. Secondary AH samples were obtained from eyes with previous intraocular surgery, prior to trabeculectomy or cataract surgery. AH (0.1 mL) was aspirated by inserting a 26-gauge needle into the anterior chamber just before surgery and then immediately stored at -80 degrees C. The ascorbic acid concentration was determined in a masked fashion by high-pressure liquid chromatography. Results: A total of 18 patients with senile cataract, 16 glaucomatous patients with primary AH (no previous intraocular surgery) and 11 glaucomatous patients with secondary AH (previous intraocular surgery) were included. There was no difference in mean age between groups (P = 0.15). The mean +/- standard deviation concentration of ascorbic acid in the secondary AH from glaucomatous patients (504 +/- 213 mu mol/L [95% confidence interval {CI}, 383-624]) was significantly lower than the concentration of ascorbic acid found in the primary aqueous of primary open-angle glaucoma (919 +/- 427 mu mol/L [95% CI, 709-1128]) and control patients (1049 +/- 433 mu mol/L [95% CI, 848-1249]; P < 0.01, Kruskal-Wallis test). Conclusions: The ascorbic acid concentration in secondary AH of glaucomatous patients was approximately twofold lower in comparison with primary AH of glaucomatous and cataract patients. The implications of a reduced concentration of ascorbic acid in the secondary AH deserve further investigation.

Auditory processing disorder in perisylvian syndrome

We hypothesized that the processing of auditory information by the perisylvian polymicrogyric cortex may be different from the normal cortex. To characterize the auditory processing in bilateral perisylvian syndrome, we examined ten patients with perisylvian polymicrogyria (Group 1) and seven control children (Group 11). Group I was composed by four children with bilateral perisylvian polymicrogyria and six children with bilateral posterior perisylvian polymicrogyria. The evaluation included neurological and neuroimaging investigation, intellectual quotient and audiological assessment (audiometry and behavior auditory tests). The results revealed a statistically significant difference between the groups in the behavioral auditory tests, Such as, digits dichotic test, nonverbal dichotic test (specifically in right attention), and random gap detection/random gap detection expanded tests. Our data showed abnormalities in the auditory processing of children with perisylvian polymicrogyria, suggesting that perisylvian polymicrogyric cortex is functionally abnormal. We also found a correlation between the severity of our auditory findings and the extent of the cortical abnormality. (C) 2009 Elsevier B.V. All rights reserved.

Quercetin inhibits UV irradiation-induced inflammatory cytokine production in primary human keratinocytes by suppressing NF-kappa B pathway

Background: Topical flavonoids, such as quercetin, have been shown to reduce ultraviolet (UV) irradiation-mediated skin damage. However, the mechanisms and signaling pathways involved in this protective effect are not clear. UV irradiation leads to activation of two major signaling pathways, namely nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1) pathways. Activation of NF-kappa B pathway by UV irradiation stimulates inflammatory cytokine expression, whereas activation of AP-1 pathway by UV irradiation promotes matrix metalloproteinase (MMP) production. Both pathways contribute to UV irradiation-induced skin damage, such as photoaging and skin tumor formation. Objective: To elucidate the underlying mechanism, we examined the effect of quercetin on UV irradiation induced activation of NF-kappa B and AP-1 pathways. Methods: Primary human keratinocytes, the major skin cell type subjected to physiological solar UV irradiation, were used to study the effects of quercetin on UV irradiation-induced signal transduction pathways. Results: Quercetin decreased UV irradiation-induced NF-kappa B DNA-binding by 80%. Consequently, quercetin suppressed UV irradiation-induced expression of inflammatory cytokines IL-1 beta (similar to 60%), IL-6 (similar to 80%), IL-8 (similar to 76%) and TNF-alpha (similar to 69%). In contrast, quercetin had no effect on UV irradiation activation of three MAP kinases, ERK, JNK, or p38. Accordingly, induction of AP-1 target genes such as MMP-1 and MMP-3 by UV irradiation was not suppressed by quercetin. Conclusion: Our data indicate that the ability of quercetin to block UV irradiation-induced skin inflammation is mediated, at least in part, by its inhibitory effect on NF-kappa B activation and inflammatory cytokine production. (C) 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Differential roles of galectin-1 and galectin-3 in regulating leukocyte viability and cytokine secretion

Galectin-1 (Gal-1) and galectin-3 (Gal-3) exhibit profound but unique immunomodulatory activities in animals but their molecular mechanisms are incompletely understood. Early studies suggested that Gal-1 inhibits leukocyte function by inducing apoptotic cell death and removal, but recent studies show that some galectins induce exposure of the common death signal phosphatidylserine (PS) independently of apoptosis. In tfhis study, we report that Gal-3, but not Gal-1, induces both PS exposure and apoptosis in primary activated human T cells, whereas both Gal-1 and Gal-3 induce PS exposure in neutrophils in the absence of cell death. Gal-1 and Gal-3 bind differently to the surfaces of T cells and only Gal-3 mobilizes intracellular Ca(2+) in these cells, although Gal-1 and Gal-3 bind their respective T cell ligands with similar affinities. Although Gal-1 does not alter T cell viability, it induces IL-10 production and attenuates IFN-gamma production in activated T cells, suggesting a mechanism for Gal-1-mediated immunosuppression in vivo. These studies demonstrate that Gal-1 and Gal-3 induce differential responses in T cells and neutrophils, and identify the first factor, Gal-3, capable of inducing PS exposure with or without accompanying apoptosis in different leukocytes, thus providing a possible mechanism for galectin-mediated immunomodulation in vivo.

Metformin pharmacokinetics in nondiabetic pregnant women with polycystic ovary syndrome

The use of metformin throughout gestation by pregnant women with polycystic ovary syndrome (PCOS) significantly reduces the number of first trimester spontaneous abortions and the rate of occurrence of gestational diabetes. The objective of this study was to investigate the pharmacokinetics and the placental transfer of metformin in pregnant women with PCOS. Eight pregnant women with PCOS taking 850 mg metformin every 12 h during the third trimester of pregnancy were evaluated. Maternal blood samples were collected at steady state during the dose interval (0-12 h). Maternal and umbilical cord blood samples were also obtained at delivery. Metformin plasma concentrations were analyzed by high-performance liquid chromatography, and pharmacokinetic parameters were determined using a non-compartmental model. Data are reported as median and minimum and maximum values. Metformin pharmacokinetic parameters were: t(A1/2), 3.8 (2.8-5.4) h; t(max), 2.0 (0.5-3.0) h; C(max), 1.4 (0.5-2.1) mg/L; C(mean), 0.5 (0.2-0.9) mg/L; AUC(0-12), 6.4 (1.1-9.2) mg h/L; Cl/f, 105 (60-274) L/h; Vd/f, 551 (385-1173) L; median fluctuation, 89 (79-95)%. Umbilical/maternal metformin plasma concentration ratios were 0.7 (0.4-1.3). Metformin oral clearance (Cl/f) had increased in our patients relative to nonpregnant healthy volunteers or diabetic patients. Therefore, lower plasma metformin concentrations were observed for nondiabetic pregnant women with PCOS. Future studies should be conducted to demonstrate the therapeutic efficacy of metformin during pregnancy. Caution is warranted as umbilical/maternal metformin plasma concentrations ratios of around 0.7 require metformin dosage adjustment.

von Wright`s Therapy to Jorgensen`s Syndrome

In his last papers about deontic logic, von Wright sustained that there is no genuine logic of norms. We argue in this paper that this striking statement by the father of deontic logic should not be understood as a death sentence to the subject. Rather, it indicates a profound change in von Wright`s understanding about the epistemic and ontological role of logic in the field of norms. Instead of a logical constructivism of deontic systems revealing a necessary structure of prescriptive discourse, which marked his earlier efforts, he adopted the view that such systems should be seem as mere objects of comparison, i.e. as providing practical standards of rationality for norm-giving activity. Within such view he proposed an interpretation of standard deontic logic in such a way to free deontic logicians from the philosophical difficulties related to the so-called Jorgensen`s dilemma and deontic paradoxes. This effort, as we claim in the present paper, is an application of Wittgenstein`s therapeutic method to dissolve philosophical difficulties caused by the use of logical tools to model relations between norms.

Longitudinal excursion and strain in the median nerve during novel nerve gliding exercises for carpal tunnel syndrome

Nerve and tendon gliding exercises are advocated in the conservative and postoperative management of carpal tunnel syndrome (CTS). However, traditionally advocated exercises elongate the nerve bedding substantially, which may induce a potentially deleterious strain in the median nerve with the risk of symptom exacerbation in some patients and reduced benefits from nerve gliding. This study aimed to evaluate various nerve gliding exercises, including novel techniques that aim to slide the nerve through the carpal tunnel while minimizing strain (sliding techniques). With these sliding techniques, it is assumed that an increase in nerve strain due to nerve bed elongation at one joint (e.g., wrist extension) is simultaneously counterbalanced by a decrease in nerve bed length at an adjacent joint (e.g., elbow flexion). Excursion and strain in the median nerve at the wrist were measured with a digital calliper and miniature strain gauge in six human cadavers during six mobilization techniques. The sliding technique resulted in an excursion of 12.4 mm, which was 30% larger than any other technique (p 0.0002). Strain also differed between techniques (p 0.00001), with minimal peak values for the sliding technique. Nerve gliding associated with wrist movements can be considerably increased and nerve strain substantially reduced by simultaneously moving neighboring joints. These novel nerve sliding techniques are biologically plausible exercises for CTS that deserve further clinical evaluation. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:972-980, 2007

Western Australian primary school teachers knowledge about childhood asthma and its management

A total of 164 primary school teachers from Perth, Western Australia anonymously completed a survey of their knowledge and attitudes about asthma. These teachers were active in assisting children with asthma management but most (91.5%) felt that they did not know enough about asthma. Attitudes toward children with asthma were positive; 97% agreed that such children should be encouraged to participate in sporting activities. Specific knowledge about asthma management and medications was, however, poor. This large sample of Western Australian teachers knew more than their European counterparts but asthma training is needed and should be targeted at improving knowledge of both regular and emergency treatments for asthma.

Familial forms broaden the horizons for primary aldosteronism

The identification of familial forms of primary aldosteronism (PAL) has led to its detection in relatives of affected patients not suspected previously of having PAL. Many ave normokalemic and some ave even normotensive. This broadens the spectrum of PAL, permitting the study of its evolution and of intervention with specific therapy when hypertension develops. The genetic basis of one form involves steroid biosynthetic enzymes and the other form predisposes to hyperplasia and benign neoplasia.

Familial partial epilepsy with variable foci: A new partial epilepsy syndrome with suggestion of linkage to chromosome 2

Familial partial epilepsy with variable foci (FPEVF) joins the recently recognized group of inherited partial epilepsies. We describe an Australian family with 10 individuals with partial seizures over four generations. Detailed electroclinical studies were performed on all affected and 17 clinically unaffected family members. The striking finding was that the clinical features of the seizures and interictal electroencephalographic foci differed among family members and included frontal, temporal, occipital, and centroparietal seizures. Mean age of seizure onset was 13 years (range, 0.75-43 years). Two individuals without seizures had epileptiform abnormalities on electroencephalographic studies. Penetrance of seizures was 62%. A genome-wide search failed to demonstrate definitive linkage, but a suggestion of linkage was found on chromosome 2q with a LOD score of 2.74 at recombination fraction of zero with the marker D2S133. FPEVF differs from the other inherited partial epilepsies where partial seizures in different family members are clinically similar. The inherited nature of this new syndrome may be overlooked because of relatively low penetrance and because of the variability in age at onset and electroclinical features between affected family members.