Lacrimal fluid peroxidase activity during the menstrual cycle

PURPOSE: The aim of this work was to investigate peroxidase activity in human tears during the various phases of the menstrual cycle. For comparative purposes saliva was also examined. METHODS: Tear fluids and saliva from 10 healthy volunteers 23-41 years of age (mean: 28.2 years), with regular menstrual cycles were sampled for the duration of at least two complete cycles. Menstrual cycles and ovulation periods were evaluated by measuring morning body temperature and hormone levels in plasma and urine. Unstimulated tears and unstimulated saliva were collected in the morning every two days. Peroxidase activity was monitored according to the 5,5'-dithiobis, 2-nitrobenzoic acid thiocyanate (Nbs-SCN) method and the protein content was determined by the Bradford method. RESULTS: Peroxidase activity in tears, expressed as U/mL, was significantly (p <.05) higher during the preovulatory and luteal phases with respect to the menses, whilst total protein content remained almost unchanged throughout all phases. A positive correlation was found between lacrimal fluid peroxidase activity and 17beta-estradiol plasma levels (p <.001). Salivary peroxidase activity did not show such estrogen-related changes. CONCLUSIONS: Our findings report cyclic variations in peroxidase activity in human tears during the menstrual cycle. Such cycling seems to reflect variations of 17 beta-estradiol plasma levels. These results suggest that a regulation of lacrimal fluid peroxidase by 17 beta-estradiol could be one possible cause for the female gender predilection in some ocular diseases, such as keratoconjunctivitis sicca.     

Heterozygous SOD1 D90A mutation presenting as slowly progressive predominant upper motor neuron amyotrophic lateral sclerosis

Of all the SOD1 gene mutations described, uniquely the D90A mutation has been identified in recessive, dominant, and apparently sporadic cases. We describe a patient with a sporadic form of amyotrophic lateral sclerosis (ALS) in which a heterozygous A > C exchange at position 272 in the SOD1 gene was detected. This mutation results in an amino acid substitution of alanine for aspartate at position 90 (D90A). The patient had a 12-year history of disease characterized by slow progression. Clinical examination at last follow-up revealed predominant upper motor neuron (p-UMN) involvement, with atrophies only in distal muscle of upper limbs. Electrophysiological examination revealed lower and upper motor neuron involvement. Family history was negative for neurological disease. This report shows that D90A in heterozygous state may cause p-UMN phenotype with very slow progression.     

Factors affecting protein thiol reactivity and specificity in peroxide reduction

Protein thiol reactivity generally involves the nucleophilic attack of the thiolate on an electrophile. A low pK(a) means higher availability of the thiolate at neutral pH but often a lower nucleophilicity. Protein structural factors contribute to increasing the reactivity of the thiol in very specific reactions, but these factors do not provide an indiscriminate augmentation in general reactivity. Notably, reduction of hydroperoxides by the catalytic cysteine of peroxiredoxins can achieve extraordinary reaction rates relative to free cysteine. The discussion of this catalytic efficiency has centered in the stabilization of the thiolate as a way to increase nucleophilicity. Such stabilization originates from electrostatic and polar interactions of the catalytic cysteine with the protein environment. We propose that the set of interactions is better described as a means of stabilizing the anionic transition state of the reaction. The enhanced acidity of the critical cysteine is concurrent but not the cause of catalytic efficiency. Protein stabilization of the transition state is achieved by (a) a relatively static charge distribution around the cysteine that includes a conserved arginine and the N-terminus of an α-helix providing a cationic environment that stabilizes the reacting thiolate, the transition state, and also the anionic leaving group; (b) a dynamic set of polar interactions that stabilize the thiolate in the resting enzyme and contribute to restraining its reactivity in the absence of substrate; but upon peroxide binding these active/binding site groups switch interactions from thiolate to peroxide oxygens, simultaneously increasing the nucleophilicity of the attacking sulfur and facilitating the correct positioning of the substrate. The switching of polar interaction provides further acceleration and, importantly, confers specificity to the thiol reactivity. The extraordinary thiol reactivity and specificity toward H(2)O(2) combined with their ubiquity and abundance place peroxiredoxins, along with glutathione peroxidases, as obligate hydroperoxide cellular sensors.     

Metabolic syndrome does not detect metabolic risk in African men living in the U.S

OBJECTIVE

Metabolic risk and metabolic syndrome (MetSyn) prevalence were compared in Africans who immigrated to the U.S. and African Americans. If MetSyn were an effective predictor of cardiometabolic risk, then the group with a worse metabolic risk profile would have a higher rate of MetSyn.

RESEARCH DESIGN AND METHODS

Cross-sectional analyses were performed on 95 men (39 Africans, 56 African Americans, age 38 ± 6 years [mean ± SD]). Glucose tolerance was determined by oral glucose tolerance test, visceral adipose tissue (VAT) was determined by computerized tomography, and MetSyn was determined by the presence of three of five factors: central obesity, hypertriglyceridemia, low levels of HDL cholesterol, hypertension, and fasting hyperglycemia.

RESULTS

MetSyn prevalence was similar in Africans and African Americans (10 vs. 13%, P = 0.74), but hypertension, glycemia (fasting and 2-h glucose), and VAT were higher in Africans.

CONCLUSIONS

African immigrants have a worse metabolic profile than African Americans but a similar prevalence of MetSyn. Therefore, MetSyn may underpredict metabolic risk in Africans.Cardiovascular disease (CVD) and type 2 diabetes (T2D) affect millions worldwide. Metabolic syndrome (MetSyn) has received global attention as a tool for identifying risk for CVD and T2D (1). Yet the value and the precise definition of MetSyn are debated (2). To reconcile the various definitions for MetSyn, five key organizations agreed in 2009 on a single definition and wrote a joint statement titled Harmonizing the Metabolic Syndrome (1). This definition requires three of five factors to be present: central obesity, hypertriglyceridemia (triglyceride [TG] ≥150 mg/dL), low HDL cholesterol (HDL-C; <40 for men, <50 for women), hypertension (blood pressure [BP] ≥130/85), and fasting hyperglycemia (glucose ≥100).Furthermore, there have been specific issues regarding the efficacy of MetSyn in people of African descent. Many investigators have independently suggested that MetSyn may not be effective in African Americans because one of the five criteria, hypertriglyceridemia, is rarely present, even when metabolic risk is high (3–5). To determine if MetSyn can detect metabolic risk in black men, we compared Africans living in the U.S. with African Americans to determine if the group with higher metabolic risk—defined by blood pressure, glycemia, and visceral adiposity—also had a higher prevalence of MetSyn.     

SEIPIN S90L Mutation in an Italian family with CMT2/dHMN and pyramidal signs

Heterozygous mutations in the Berardinelli–Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot–Marie–Tooth disease type 2 (CMT2) with predominant hand involvement. We studied an Italian family with a CMT2 phenotype with pyramidal signs that had subclinical sensory involvement on sural nerve biopsy. Direct sequencing analysis of the BSCL2 gene in the three affected siblings revealed an S90L mutation. This report confirms the variability of clinical phenotypes associated with a BSCL2 Ser90Leu mutation and describes the first Italian family with this mutation. Muscle Nerve, 2010     

Oral frailty indicators to target major adverse health-related outcomes in older age: a systematic review

GeroScience - A well-preserved oral function is key to accomplishing essential daily tasks. However, in geriatric medicine and gerodontology, as age-related physiological decline disrupts several...     

Effect of oral contraceptives on lacrimal fluid peroxidase activity in women

Lacrimal fluid peroxidase has been supposed to be involved in the protection against oxidative damage to the ocular surface. Our recent findings showed the existence of significant cyclic variations in lacrimal fluid peroxidase activity that were positively correlated with those of 17beta-estradiol plasma levels throughout the menstrual cycle of fertile women. In the present study lacrimal fluid peroxidase activity of 8 healthy normocyclic women using low-dose oral contraceptives during the monthly cycle was determined. Data showed that low-dose oral contraceptives caused a decrease in lacrimal fluid peroxidase activity and a lack of its cyclic pattern with respect to the enzyme activity of 8 untreated age-matched women. Moreover, this result suggests that lacrimal fluid peroxidase activity could be regulated by estrogen.     

Effect of anti TNFalpha therapy on arterial diameter and wall shear stress and HDL cholesterol

It has been recently hypothesized that both TNFalpha and anti TNFalpha treatment have a stimulating effect on nitric oxide synthesis and release. Moreover, an in vitro experiment has demonstrated that HDL-cholesterol binds TNFalpha. Aims of our study were to investigate wall shear stress of peripheral arteries and endothelial function of brachial artery in subjects with Rheumatoid Arthritis (RA) at baseline and after infliximab. Moreover, we evaluated the effect of anti TNFalpha therapy on lipid profile. Ten patients with RA received infliximab therapy at weeks 0, 2 and 6. Lipids and vascular parameters were measured before and the day after each infusion. After the first treatment, FMD increased (3.7 +/- 1.9% versus 17.5 +/- 2.9%, P <0.01) and common carotid and brachial artery diameters decreased (5.9 +/- 0.2 mm versus 5.5 +/- 0.2 mm; 3.5 +/- 0.4 mm versus 3.1 +/- 0.4 mm, respectively, P <0.005). Common carotid and brachial artery wall shear stress increased (21.1 +/- 1.1 dynes/cm2 versus 23.9 +/- 1.4 dynes/cm2; 42.0 +/- 4.7 dynes/cm2 versus 51.6 +/- 5.7 dynes/cm2, P <0.01). Similar results were observed after the second and third infusion. All these parameters returned to pre-treatment level at the following infusion. HDL-cholesterol and apolipoprotein AI significantly decreased after each treatment (1st treatment: 1.4 +/- 0.05 mmol/L versus 1.2 +/- 0.06 mmol/L, P <0.01; 1.73 +/- 0.05 g/L versus 1.57 +/- 0.02 g/L, P <0.03). The present data show vasoconstriction and an increase of wall shear stress in studied arteries after infliximab. HDL cholesterol is reduced by treatment and does not seem to influence FMD.