Plasma folate levels are associated with the lipoprotein profile: a retrospective database analysis

BACKGROUND: Several studies demonstrated an association of homocysteine plasma levels and the plasma lipoprotein profile. This cross-sectional pilot study aimed at analyzing whether blood levels of the two important cofactors of homocysteine metabolism, folate and vitamin B12, coincide with the lipoprotein profile. METHODS: In a retrospective single center approach, we analyzed the laboratory database (2003-2006) of the University Hospital Bonn, Germany, including 1743 individuals, in whom vitamin B12, folate and at least one lipoprotein parameter had been determined by linear multilogistic regression. RESULTS: Higher folate serum levels were associated with lower serum levels of low density lipoprotein cholesterol (LDL-C; Beta = -0.164; p < 0.001), higher levels of high density lipoprotein cholesterol (HDL-C; Beta = 0.094; p = 0.021 for trend) and a lower LDL-C-C/HDL-C-ratio (Beta = -0.210; p < 0.001). Using ANOVA, we additionally compared the individuals of the highest with those of the lowest quartile of folate. Individuals of the highest folate quartile had higher levels of HDL-C (1.42 +/- 0.44 mmol/l vs. 1.26 +/- 0.47 mmol/l; p = 0.005), lower levels of LDL-C (3.21 +/- 1.04 mmol/l vs. 3.67 +/- 1.10 mmol/l; p = 0.001) and a lower LDL-C/HDL-C- ratio (2.47 +/- 1.18 vs. 3.77 +/- 5.29; p = 0.002). Vitamin B12 was not associated with the lipoprotein profile. CONCLUSION: In our study sample, high folate levels were associated with a favorable lipoprotein profile. A reconfirmation of these results in a different study population with a well defined status of health, diet and medication is warranted

Acute Lead Exposure Increases Arterial Pressure: Role of the Renin-Angiotensin System

Background: Chronic lead exposure causes hypertension and cardiovascular disease. Our purpose was to evaluate the effects of acute exposure to lead on arterial pressure and elucidate the early mechanisms involved in the development of lead-induced hypertension. Methodology/Principal Findings: Wistar rats were treated with lead acetate (i.v. bolus dose of 320 μg/Kg), and systolic arterial pressure, diastolic arterial pressure and heart rate were measured during 120 min. An increase in arterial pressure was found, and potential roles of the renin-angiotensin system, Na+,K+-ATPase and the autonomic reflexes in this change in the increase of arterial pressure found were evaluated. In anesthetized rats, lead exposure: 1) produced blood lead levels of 37±1.7 μg/dL, which is below the reference blood concentration (60 μg/dL); 2) increased systolic arterial pressure (Ct: 109±3 mmHg vs Pb: 120±4 mmHg); 3) increased ACE activity (27% compared to Ct) and Na+,K+-ATPase activity (125% compared to Ct); and 4) did not change the protein expression of the α1-subunit of Na+,K+-ATPase, AT1 and AT2. Pre-treatment with an AT1 receptor blocker (losartan, 10 mg/Kg) or an ACE inhibitor (enalapril, 5 mg/Kg) blocked the lead-induced increase of arterial pressure. However, a ganglionic blockade (hexamethonium, 20 mg/Kg) did not prevent lead's hypertensive effect. Conclusion: Acute exposure to lead below the reference blood concentration increases systolic arterial pressure by increasing angiotensin II levels due to ACE activation. These findings offer further evidence that acute exposure to lead can trigger early mechanisms of hypertension development and might be an environmental risk factor for cardiovascular diseaseThis study was supported by grants from CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico)/FAPES (Fundação de Amparo à Pesquisa do Espírito Santo)/FUNCITEC (Fundação de Ciência e Tecnologia)(39767531/07), Brazil and from MCINN (Ministerio de Ciencia e Innovación) (SAF 2009- 07201) and ISCIII (Instituto de Salud Carlos III) (Red RECAVA- Red Temática de Investigación en Enfermedades Cardiovasculares del Instituto de Salud Carlos III, RD06/0014/0011), Spai

Oksidacijski stres u lakirera izloženih niskim razinama olova

Lead toxicity is a public health problem particularly to the children and to occupationally exposed adults. Evidence is mounting successively regarding the adverse health effects of lead at low levels. This study was undertaken to assess the antioxidant status of lead-exposed residential and commercial painters of Lucknow city in Uttar Pradesh, India. Thirty-five painters aged 20 to 50 years who had blood lead levels ≤400 µg L-1 were selected for the study from a population of 56 male painters initially screened for blood lead. The control group included an equal number of subjects of the same age group without any occupational exposure to lead. We studied the association between low lead level exposure and antioxidant status and found that blood lead levels in painters were approximately seven times as high as in controls [(219.2 ± 61.9) µg L-1 vs. (30.6±10.1) µg L-1, respectively]. Among the biomarkers of lead toxicity a significant decrease in the level of delta-aminolevulinic acid dehydratase [(9.13±4.62) UL-1 vs. (39.38±5.05) UL-1] and an increase in the level of zinc protoporphyrin [(187.9±49.8) µg L-1 vs. (26.4±5.5) µg L-1] were observed in painters compared to controls. Among antioxidant enzymes, painters showed a significant decrease in catalase [(56.77±11.11) UL-1 vs. (230.30±42.55) UL-1] and superoxide dismutase [(0.64±0.19) UL-1 vs. (2.68±0.62) UL-1] compared to controls. Lipid peroxidation was monitored by measuring thiobarbituric acid reactive substances (TBARS) that were expressed in terms of malondialdehyde (MDA) equivalents. Concentration of MDA in plasma was higher in painters than in controls [(7.48±1.31) nmol mL-1 vs. (3.08±0.56) nmol mL-1]. Significant changes were also observed in reduced and oxidised glutathione levels. The strong association between blood lead levels and oxidative stress markers in this population suggests that oxidative stress should be considered in the pathogenesis of lead-related diseases among people with low level environmental exposure to lead.Toksičnost olova javnozdravstveni je problem, napose u djece i odraslih osoba koje su im izložene profesionalno. Sve je više dokaza o štetnom djelovanju olova pri niskim razinama. Svrha je ovog ispitivanja bila procijeniti antioksidacijski status u lakirera iz grada Lucknowa u indijskoj pokrajini Uttar Pradesh. Iz skupine od 56 muškaraca lakirera u dobi od 20 do 50 godina s pozitivnim početnim nalazima olova u krvi, za ispitivanje su izabrana 35-orica čije su razine iznosile ≤400 µg L-1. Izabran je i jednaki broj kontrolnih ispitanika iz iste dobne skupine, koji nisu bili profesionalno izloženi olovu. Ispitana je povezanost izme|u izloženosti niskim razinama olova i antioksidacijskoga stanja te je utvrđeno da su razine olova u krvi lakirera [(219,2±61,9) µg L-1] bile oko sedam puta više negoli u kontrolnih ispitanika [(30,6±10,1) µg L-1]. Od biopokazatelja toksičnosti olova u lakirera je zamijećen značajan pad razina delta- ALAD [(9,13±4,62) UL-1 prema (39,38±5,05) UL-1] te rast razina cinkova protoporfirina [(187,9±49,8) µg L-1 prema (26,4±5,5) µg L-1] u odnosu na kontrolne ispitanike. Od antioksidacijskih enzima u lakirera je značajno pala aktivnost katalaze [(56,77±11,11) UL-1 prema (230,30±42,55) UL-1] i superoksid dismutaze [(0,64±0.19) UL-1 prema (2,68±0,62) UL-1] u odnosu na kontrolu, dok je produkt lipidne peroksidacije u plazmi (izv. thiobarbituric acid reactive substances, TBARS) izražen kao koncentracija malondialdehida (MDA) porastao [(7,48±1,31) nmol mL-1 prema (3,08±0,56) nmol mL-1]. Značajne su promjene također zamijećene u smanjenim razinama glutationa i njihovoj oksidaciji. Snažna povezanost razina olova u krvi s pokazateljima oksidacijskoga stresa upućuje na to da u osoba s niskom razinom izloženosti olovu iz okoliša kod razmatranja patogeneze bolesti povezane s olovom u obzir valja uzeti oksidacijski stres

Conducting poliesters for biomedical applications

In this work polymers possessing both electrical conducting properties and biodegradability were synthesized and employed for scaffolds preparation. The synthetic strategy consisted in grafting polyaniline chains to the backbone of carboxylated segmented polyesterurethanes. After doping, grafted polymers showed electrical conductivity values of about 10-5 S/cm and resulted not cytotoxic. Preliminary experiments using these materials for scaffolds preparation evidenced their ability to develop three-dimensial porous structures

Mevalonate kinase deficiency associated with ataxia and retinitis pigmentosa in two brothers with MVK gene mutations

Purpose: To report the clinical and molecular genetic findings in two brothers with retinitis pigmentosa (RP) and mevalonate kinase deficiency (MKD). Methods: The brothers were examined clinically and with fundus autofluorescence, near-infrared auto fluorescence, and Spectral domain optical coherence tomography. Targeted resequencing was done with a custom designed gene panel containing 78 genes associated with RP. Mutations were confirmed by direct Sanger sequencing. Results: Both brothers, aged 46 and 47 years, were found to carry compound heterozygous mutations in the MVK gene (c.59A>C, c.1000G>A) encoding mevalonate kinase. They presented with severe ataxia, pseudophakia due to early onset cataract, and progressed retinitis pigmentosa. In one brother with cystoid macular edema, treatment with dorzolamide was beneficial. Serum IgD levels were markedly increased in both brothers and mevalonic acid blood and urine levels were markedly increased in, the one brother who could be examined. The disease severity differed between the brothers one had more severe ataxia and less severe visual deficiency compared to the other. Conclusion: MKD can be associated with RP and early onset cataract. Most MKD patients developing RP carry the (p.Ala334Thr) mutation. Macular edema can be treated using local dorzolamide

Inherited Retinal or Optic Nerve Disorders – Five Steps to Diagnosis (Originaltitel: Erbliche Netzhaut- und Sehbahnerkrankungen – 5 Schritte zur Diagnose)

An early diagnosis of inherited retinal or optic nerve disorders is often delayed due to unspecific clinical signs, multiple clinical manifestations and striking genetic heterogeneity of the underlying molecular defects. This study represents a retrospective analysis of findings in 4,021 patients with inherited retinal or optic nerve disorders seen between 1986 and 2014 (1,171 with follow-up). In addition to the basic ophthalmological examination, electrophysiological tests (ERG, n = 2,088, since 1986; EOG, n = 381, since 1986; VEP n = 595, since 1986; mfERG, n = 819, since 1998) and non-invasive retinal imaging (fundus autofluorescence (FAF, n = 1,784, since 2002), near-infrared autofluorescence (NIA, n = 1,091, since 2006), spectral domain OCT (SD-OCT, n = 848, since 2008) and three-wavelengths multicolour spectral reflection imaging (MC, n = 366, since 2013) were performed at least once. Molecular DNA testing was done in 383 patients between 2006 and 2014. Based on these data an efficient diagnostic strategy is suggested: 1) inclusion of inherited retinal and optic nerve disorders into the differential diagnosis of visual loss or visual field defects with undefined causes; 2) non-invasive retinal imaging; 3) electrophysiological tests; 4) DNA testing to confirm the initial clinical diagnosis; 5) examination in specialised centres, therapy and follow-up. In recent years, the spectrum of diagnostic techniques has continuously expanded. Importantly, non-invasive retinal imaging has become the primary diagnostic tool and DNA testing based on state-of-the-art high throughput techniques increases the identification of associated gene mutations. In conclusion, a structured process in the diagnostic procedure of inherited retinal and optic nerve disorders greatly reduces a diagnostic delay, enables an earlier counselling and therapy and avoids further unnecessary diagnostic tests

Fundus Autofluorescence and SD-OCT Document Rapid Progression in Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC) Associated with a c.256G > A Mutation in BEST1

Purpose: To report the variability of clinical findings, rapid concentric progression, and successful treatment of macular edema in autosomal dominant vitreoretinochoroidopathy (ADVIRC) associated with a heterozygous c.256G > A missense mutation in the bestrophin-1 (BEST1) gene. Methods: Three affected members of a four-generation ADVIRC family were examined with fundus autofluorescence (FAF), near-infrared autofluorescence (NIA) and spectral domain optical coherence tomography (SD-OCT). Direct sequence analysis of coding and flanking intronic regions of the BEST1 gene was performed. Results: Disease manifestations presented with high variability with visual problems manifesting between 10 and 40 years of age. Two probands showed marked signs of peripheral degeneration, while this retinal area was not noticeably affected in the third. Cystoid macular edema was present in one proband, which responded to long-term treatment with topic dorzolamide with improved visual acuity. FAF and NIA revealed mid-peripheral retinal degeneration in areas that appeared normal on ophthalmoscopy. The full-field ERG was markedly reduced in two probands. Within a 5-year period a marked increase in concentric progression of degeneration including the posterior pole was documented with FAF, NIA and SD-OCT in one proband after the age of 63 years. Direct sequence analysis of the BEST1 gene revealed a heterozygous c.256G > A missense mutation in the three affected probands. Conclusion: The findings in this family emphasize the previously noted variability of clinical manifestations in BEST1-associated ADVIRC and the relevance of FAF and NIA imaging. Cystoid macular edema and vascular leakage can be successfully treated using dorzolamide