Significant disparity in base and sugar damage in DNA resulting from neutron and electron irradiation

In this study, a comparison of the effects of neutron and electron irradiation of aqueous DNA solutions was investigated to characterize potential neutron signatures in DNA damage induction. Ionizing radiation generates numerous lesions in DNA, including base and sugar lesions, lesions involving base–sugar combinations (e.g. 8,5′-cyclopurine-2′-deoxynucleosides) and DNA–protein cross-links, as well as single- and double-strand breaks and clustered damage. The characteristics of damage depend on the linear energy transfer (LET) of the incident radiation. Here we investigated DNA damage using aqueous DNA solutions in 10 mmol/l phosphate buffer from 0–80 Gy by low-LET electrons (10 Gy/min) and the specific high-LET (∼0.16 Gy/h) neutrons formed by spontaneous ²⁵²Cf decay fissions. 8-hydroxy-2′-deoxyguanosine (8-OH-dG), (5′R)-8,5′-cyclo-2′-deoxyadenosine (R-cdA) and (5′S)-8,5′-cyclo-2′-deoxyadenosine (S-cdA) were quantified using liquid chromatography–isotope-dilution tandem mass spectrometry to demonstrate a linear dose dependence for induction of 8-OH-dG by both types of radiation, although neutron irradiation was ∼50% less effective at a given dose compared with electron irradiation. Electron irradiation resulted in an exponential increase in S-cdA and R-cdA with dose, whereas neutron irradiation induced substantially less damage and the amount of damage increased only gradually with dose. Addition of 30 mmol/l 2-amino-2-(hydroxymethyl)-1,3-propanediol (TRIS), a free radical scavenger, to the DNA solution before irradiation reduced lesion induction to background levels for both types of radiation. These results provide insight into the mechanisms of DNA damage by high-LET ²⁵²Cf decay neutrons and low-LET electrons, leading to enhanced understanding of the potential biological effects of these types of irradiation.     

Mathematical Modeling and Experimental Substantiation of the Gas Release Process in the Production of Non-Autoclaved Aerated Concrete

The widespread use of aerated concrete in construction has led to the emergence of many types and compositions. However, additional research should fill theoretical gaps in the phenomenon of gas release during the formation of the structure of aerated concrete. Based on theoretical analysis and experimental studies, the article proposes a mathematical model of the swelling process based on the physicochemical laws of convection and molecular diffusion of hydrogen from a mixture and the conditions of swelling, precipitation, and stabilization of the mixture. An improved method for the manufacture of aerated concrete is proposed, which consists of introducing cement pre-hydrated for 20–30 min into the composition of the aerated concrete mixture and providing improved gas-holding capacity and increased swelling of the mixture, reducing the average density of aerated concrete up to 29% and improving heat-shielding properties up to 31%. At the same time, the small dynamics of a decrease in the strength properties of aerated concrete were observed, which is confirmed by an increased structural quality factor (CSQ) of up to 13%. As a result, aerated concrete has been obtained that meets the requirements of environmental friendliness and has improved mechanical and physical characteristics. Economic efficiency is to reduce the cost of production of aerated concrete and construction in general by about 15%.     

Vertebral hemangiomas: diagnosis, management, natural history and clinicopathological correlates in 86 patients

BACKGROUND Vertebral hemangiomas are characterized by diverse clinical histories, radiological features, and results of surgical treatment. It still remains unclear how these differences in clinical behavior relate to pathological type.

METHODS A retrospective diagnostic, surgical, and histopathological study of 86 consecutive patients with various pathological types of vertebral hemangioma was performed to establish clinicopathological correlates.

RESULTS The study confirmed that differences exist in clinical course, appearance on imaging, and outcomes in pathological types of hemangiomas. Based on these findings the authors attempted to identify signs characterizing each group.

CONCLUSIONS Differences in clinical history and radiological features exist among pathological types of vertebral hemangiomas. These differences cannot precisely predict the type pathology before histologic examination, but do help us to understand the natural history of such lesions more fully.     

Third-generation,self-inactivating gp91(phox) lentivector corrects the oxidase defect in NOD/SCID mouse-repopulating peripheral blood-mobilized CD34+ cells from patients with X-linked chronic granulomatous disease

HIV-1-derived lentivectors are promising for gene transfer into hematopoietic stem cells but require preclinical in vivo evaluation relevant to specific human diseases. Nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice accept human hematopoietic stem cell grafts, providing a unique opportunity for in vivo evaluation of therapies targeting human hematopoietic diseases. We demonstrate for the first time that hematopoietic stem cells from patients with X-linked chronic granulomatous disease (X-CGD) give rise to X-CGD-phenotype neutrophils in the NOD/SCID model that can be corrected using VSV-G-pseudotyped, 3rd-generation, self-inactivating (SIN) lentivector encoding gp91(phox). We transduced X-CGD patient-mobilized CD34(+) peripheral blood stem cells (CD34(+)PBSCs) with lentivector-gp91(phox) or amphotropic oncoretrovirus MFGS-gp91(phox) and evaluated correction ex vivo and in vivo in NOD/SCID mice. Only lentivector transduced CD34(+)PBSCs under ex vivo conditions nonpermissive for cell division, but both vectors performed best under conditions permissive for proliferation (multiple growth factors). Under the latter conditions, lentivector and MFGS achieved significant ex vivo correction of X-CGD CD34(+)PBSCs (18% and 54% of cells expressing gp91(phox), associated with 53% and 163% of normal superoxide production, respectively). However, lentivector, but not MFGS, achieved significant correction of human X-CGD neutrophils arising in vivo in NOD/SCID mice that underwent transplantation (20% and 2.4%, respectively). Thus, 3rd-generation SIN lentivector-gp91(phox) performs well as assessed in human X-CGD neutrophils differentiating in vivo, and our studies suggest that the NOD/SCID model is generally applicable for in vivo study of therapies evaluated in human blood cells expressing a specific disease phenotype.     

Beneficial effects versus toxicity of medium-chain triacylglycerols in rats with NASH

BACKGROUND/AIMS: Replacing long-chain triacylglycerols (LCT) with medium-chain triacylglycerols (MCT) reduces alcohol-induced liver injury. Because of the similarity of the pathogenesis of alcohol-induced liver damage and non-alcoholic steatohepatitis (NASH), our aim was to assess whether MCT is also beneficial in NASH. METHODS: We used a rat NASH model in which corn oil (35% of total calories) was isocalorically replaced with MCT. RESULTS: Partial replacement of LCT did not ameliorate hepatic fat accumulation, 4-hydroxynonenal, collagen type I and its mRNA but it increased TNF-alpha and its mRNA (p<0.001). However, in rats given the high-fat diet restricted to 2/3 of the amount they were consuming, these adverse effects decreased, with and without MCT including less liver steatosis and lower triacylglycerols, but without beneficial effects of MCT. When 70% of the fat calories were replaced with MCT with no LCT remaining in the diet, no steatosis developed and hepatic TNF-alpha was low. When all MCT were given with carbohydrates (instead of LCT) hepatic TNF-alpha also decreased (p<0.001). CONCLUSIONS: MCT are not hepatotoxic, provided the diet contains no significant amount of LCT. Total replacement of dietary LCT with MCT fed ad libitum is beneficial whereas partial replacement becomes hepatotoxic, unless the dietary intake is restricted.     

Recommendations for management of dyslipidemia in high cardiovascular risk patients

Overwhelming evidence supports a causal relationship between elevated levels of plasma cholesterol, particularly low-density lipoprotein cholesterol, and increased risk of coronary artery disease, which remains the leading cause of death and morbidity worldwide. Low-density lipoprotein cholesterol lowering has been the main goal of therapy, and clinical trial results from recently published studies of intensive statin therapy confirm the benefits of more aggressive lipid-lowering targets, particularly in subjects at high risk for cardiovascular events. This management update will focus on the implications of risk reduction in patients at high cardiovascular risk, and will provide practical steps to help further risk stratify these patients and help them reach their target goals.     

Memory impairments and oxidative stress in the hippocampus of in-utero cocaine-exposed rats

We examined whether significant oxidative stress is induced in the brain of juvenile rats exposed in utero to cocaine, and contributes to their mnesic difficulties. We measured nitric oxide generation, using electron paramagnetic resonance, and the thiobarbituric acid reactive species as specific indexes of lipid peroxidation. Both nitric oxide and lipid peroxidation were elevated in the hippocampus of in-utero cocaine-exposed rats as compared with control animals. In-utero cocaine-exposed rats developed significant learning impairments in the water-maze, shown by probe test retrieval deficits. In parallel, behavioural sessions resulted in increases of thiobarbituric acid reactive species levels only in control animals. Therefore, in-utero cocaine exposure resulted in a significant oxidative stress in basal conditions, which may be related to impaired learning ability.