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[en] Ellagic acid (EA) has been gaining a considerable attention in recent years. The interest in non-drug and herbal base therapies is being increased. EA is a biological molecule found in different fruits and seeds, which is known to have the ability to scavenge reactive oxygen radicals. It has been observed that methyl tert-butyl ether (MTBE) has destructive effects on structure and function of hemoglobin (Hb), an important respiratory blood protein. This conclusion is reached from our far-UV circular dichroism, Soret band absorption, fluorescence and oxygen affinity measurements. It has also been observed from our chemiluminscence measurements that ROS production is increased in the presence of MTBE which degrades heme in Hb. The main goal of this study was to offer a way to scavenge ROS produced during MTBE interaction with Hb. We report that EA decreased the heme degradation and ROS production in Hb solutions containing MTBE. - Highlights: • Hemoglobin structure and function were disturbed in the presence of methyl tert-butyl ether (MTBE). • Heme degradation was increased due to production of reactive oxygen specious. • Deleterious effects of reactive oxygen specious were reduced by ellagic acid.
[en] Background: Acrylamide-induced immunotoxicity and allergic dermatitis have been reported in animal experiments and clinical reports, respectively. However, epidemiological evidence from the general population is limited. Objectives: The purpose of the present study was to estimate the associations between acrylamide exposure and allergy-related outcomes in the general US population. Methods: A total of 6982 subjects were selected from the National Health and Nutrition Examination Survey 2005–2006 (NHANES). Internal exposure was measured by the hemoglobin adducts of acrylamide (HbAA) and its metabolite glycidamide (HbGA). Allergy-related outcomes including asthma, hay fever, allergy, itchy rash, sneeze, wheeze and eczema were obtained by self-administered questionnaires. Allergic sensitization was assessed by the total immunoglobulin E (IgE) levels. The associations of HbAA and HbGA quartiles with allergy-related outcomes were calculated using logistic regression models with multivariable adjustments. Analyses were additionally stratified according to age, gender and serum cotinine levels. Results: When setting quartile 1 of HbAA as reference, the odds ratios (ORs) [95% confidence intervals (CIs)] of quartile 2 to 4 for eczema were 1.18 (0.79–1.76), 1.14 (0.73–1.78) and 1.58 (1.14–2.18), respectively (ptrend = 0.002). Individuals at the highest quartile of HbGA had significantly elevated likelihoods of itchy rash (OR = 1.37, 95% CI = 1.02–1.83, ptrend = 0.032) and eczema (OR = 1.45, 95% CI = 1.06–1.97, ptrend = 0.044). The stratification analyses indicated various results in different subgroups. Conclusions: This study indicated significant associations between HbAA and HbGA levels and the likelihoods of allergy-related outcomes in the general US population, depending on age, gender and smoke exposure status. These findings suggested potential public health concerns for the widespread exposure to acrylamide. - Highlights: • Health effects of acrylamide and glycidamide on allergy-related outcomes were assessed in the general US population. • Elevated HbAA levels are associated with increased likelihoods of eczema. • Elevated HbGA levels are associated with increased likelihoods of itchy rash and eczema. • Associations between HbAA and HbGA levels and allergy-related outcomes varied by age, gender and serum cotinine levels. - Levels of HbAA and HbGA are significantly associated with allergy-related outcomes in the general US population.
[en] Highlights: • Cell-free hemoglobin (CFH) increases endothelial barrier permeability. • Endothelial ascorbate is depleted following exposure to CFH. • Treatment of endothelial cells with ascorbate attenuates CFH mediated permeability. Increased endothelial permeability is central to shock and organ dysfunction in sepsis but therapeutics targeted to known mediators of increased endothelial permeability have been unsuccessful in patient studies. We previously reported that cell-free hemoglobin (CFH) is elevated in the majority of patients with sepsis and is associated with organ dysfunction, poor clinical outcomes and elevated markers of oxidant injury. Others have shown that Vitamin C (ascorbate) may have endothelial protective effects in sepsis. In this study, we tested the hypothesis that high levels of CFH, as seen in the circulation of patients with sepsis, disrupt endothelial barrier integrity.
[en] Although nicotinamide administration has increased the radiosensitivity of experimental tumors, there is a scarcity of data detailing the underlying physiological mechanisms. The current study presents a method for quantifying both microregional distributions of intravascular HbO2 saturations and the presence or absence of blood flow in adjacent frozen tumor sections. Two murine tumor cell lines, KHT and SCCVII, were implanted and quick-frozen without the use of anesthetics. Nicotinamide was administered IP 1 h prior to freezing, and a fluorescent dye that preferentially stains cells adjacent to blood vessels was injected IV 1 min prior to freezing. To visualize the presence or absence of blood flow, six micron sections were first cut using a cryostat. The remaining frozen tumor block was then analyzed cryospectrophotometrically to determine intravascular HbO2 levels. While KHT HbO2 levels increased somewhat predictably following nicotinamide, the response in SCCVII tumors varied with distance from the tumor surface. Near the periphery, SCCVII HbO2 levels increased, but nearer the tumor center, HbO2 levels actually decreased. Perfused blood vessels were uniformly distributed throughout the tumor volume except in regions of necrosis. Even vessels containing no measurable oxygen remained perfused, as evidenced by the presence of the fluorescent marker. These results demonstrate that nicotinamide raises intravascular HbO2 saturations in both KHT and SCCVII tumors. This increase in oxygen delivery is not evenly distributed throughout the tumor volume in spite of a uniform distribution of perfused blood vessels. Blood flow in a substantial proportion of these vessels is most likely not sufficiently rapid to serve a functional purpose in terms of oxygen supply to the surrounding tumor tissue. 15 refs., 4 figs
[en] We prepared silica nanospheres 360 nm in diameter surface-modified with p-tert-butylthiacalixarenes containing amine, carboxyl, and guanidinium groups. We found that these silica nanoparticles selectively adsorb model oligonucleotides and proteins. The particles modified with the macrocycle containing guanidinium fragments selectively adsorbed long-chain oligonucleotides and those modified with the macrocycle containing amine groups adsorbed BSA and hemoglobin with pH-dependent selectivity. We compared this behavior with that of silica nanoparticles carrying amine and carboxyl groups, and concluded that both electrostatic interactions and specific binding are responsible for the observed selectivity
[en] Highlights: • Bovine vitreous protected cultured neurons from the oxidative toxicity of hemoglobin. • Complete neuroprotection was provided by a 3% vitreous solution. • Ascorbate accounted for most protection in diluted vitreous. • Transferrin and selenium content may contribute in undiluted vitreous. • Vitreous may protect adjacent neurons from hemorrhagic injury. Hemorrhage into the brain parenchyma or subarachnoid space is associated with edema and vascular injury that is likely mediated at least in part by the toxicity of hemoglobin. In contrast, extravascular blood appears to be less neurotoxic when localized to the retina or adjacent vitreous, the gel filling the posterior segment of the eye. In this study, the hypothesis that vitreous protects neurons from hemoglobin toxicity was investigated in a primary cortical cell culture model. Consistent with prior observations, hemoglobin exposure for 24 h resulted in death of most neurons without injury to co-cultured glia. Neuronal loss was reduced in a concentration-dependent fashion by bovine vitreous, with complete protection produced by 3% vitreous solutions. This effect was associated with a reduction in malondialdehyde but an increase in cell iron. At low vitreous concentrations, its ascorbate content was sufficient to account for most neuroprotection, as equivalent concentrations of ascorbate alone had a similar effect. However, other vitreous antioxidants provided significant protection when applied at concentrations present in undiluted vitreous, and prevented all neuronal loss when combined in the absence of ascorbate. These results indicate that vitreous is an antioxidant cocktail that robustly protects neurons from hemoglobin toxicity, and may contribute to the relative resistance of retinal neurons to hemorrhagic injury.
[en] Highlights: • Defect of βE-globin pre-mRNA splicing was repaired by engineered splice-switching U7 snRNA. • Splice-switching oligonucleotide sequence was identified by a two-step tiling approach. • The engineered U7 snRNA improve pathology of erythroid cells from thalassemia patients. Repair of a splicing defect of β-globin pre-mRNA harboring hemoglobin E (HbE) mutation was successfully accomplished in erythroid cells from patients with β-thalassemia/HbE disorder by a synthetic splice-switching oligonucleotide (SSO). However, its application is limited by short-term effectiveness and requirement of lifelong periodic administration of SSO, especially for chronic diseases like thalassemias. Here, we engineered lentiviral vectors that stably express U7 small nuclear RNA (U7 snRNA) carrying the splice-switching sequence of the SSO that restores correct splicing of βE-globin pre-mRNA and achieves a long-term therapeutic effect. Using a two-step tiling approach, we systematically screened U7 snRNAs carrying splice-switching SSO sequences targeted to the cryptic 5′ splice site created by HbE mutation. We tested this approach and identified the most responsive element for mediating splicing correction in engineered U7 snRNAs in HeLa-βE cell model cell line. Remarkably, the U7 snRNA lentiviral vector (U7 βE4+1) targeted to this region effectively restored the correctly-spliced βE-globin mRNA for at least 5 months. Moreover, the effects of the U7 βE4+1 snRNA lentiviral vector were also evident as upregulation of the correctly-spliced βE-globin mRNA in erythroid progenitor cells from β-thalassemia/HbE patients treated with the vector, which led to improvements of pathologies in erythroid progenitor cells from thalassemia patients. These results suggest that the splicing correction of βE-globin pre-mRNA by the engineered U7 snRNA lentiviral vector provides a promising, long-term treatment for β-thalassemia/HbE.
[en] Malaria has protean clinical manifestations and renal complications, particularly acute renal failure that could be life threatening. To evaluate the incidence, clinical profile, ou come and predictors of mortality in patients with malarial acute renal failure, we retrospectively studied the last two years records of malaria induced acute renal failure in patients with peripheral smear positive for malarial parasites. One hundred (10.4%) (63 males, 37 females) malaria induced acute renal failure amongst 958 cases of acute renal failure were evaluated. Plasmodium (P). falciparum was reported in 85%, P. vivax in 2%, and both in 13% patients. The mean serum creatinine was 9.2 ± 4.2 mg%, and oligo/anuria was present in 82%; 78% of the patients required hemodialysis. Sixty four percent of the patients recovered completely, 10% incompletely, and 5% developed chronic kidney failure; mortality occurred in 21% of the patients. Low hemoglobin, oligo/anuria on admission, hyperbilirubinemia, cerebral malaria, disseminated intravascular coagulation, and high serum creatinine were the main predictors of mortality. We conclude that malaria is associated with acute renal failure, which occurs most commonly in plasmodium falciparum infected patients. Early diagnosis and prompt dialysis with supportive management can reduce morality and enhance recovery of renal function (Author).