Greater Protective Effect Research Articles

Type 2 diabetes preventive effects with a 12-months sardine-enriched diet in elderly population with prediabetes: An interventional, randomized and controlled trial

Fish could play a role in preventing type 2 diabetes (T2D) but there has been little specification about the type of fish and the preventive mechanism involved in its health claim. The sardine is a source of omega-3 and taurine that, in isolation or in synergy, would produce T2D-delaying through different molecular mechanism. The consumption of twice a week of sardine, during one year would reduce T2D-developing risk in a population with prediabetes (preDM) and old age. 152 subjects with fasting glucose between 100-124 mg/dL aged ≥65 yo were recruited from three primary care centers in Barcelona and were randomly distributed among two interventional groups: control group (CG) and sardine group (SG). Both groups received same T2D-prevention nutritional during a year but only SG had to add 200 g of sardine per week. All variables were collected before to start and at the end of the diet. (ClinicalTrials.gov: NCT03557541). 152 people were randomized into CG (n=77) and SG (n=75) with 18 and 12 drop outs respectively. Subjects in SG, significantly compared to CG, decreased percentage classified-individuals in a very high risk group to develop T2D according to FINDRISC (p=0.035). In addition to increasing HDL-cholesterol and adiponectin and decreasing triglycerides (p<0.05) and blood pressure (<0.05), SG showed a lower HOMA-IR (p=0.032). The consumption of sardine characteristics nutrients as omega-3, EPA and DHA, vitamin D, fluorine and taurine were higher for SG (p<0.05). These results agreed with the increased of taurine, fatty acid (FA) omega-3 and bile acids circulating metabolites (p<0.05). Changes erythrocyte membrane FA were detected only in SG with a decrease of 5 omega-6 FA (p<0.001) and an increase of 3 omega-3 FA types (p<0.001). We conclude that a year T2D-prevention diet with sardine supplementation has a greater protective effect against developing T2D and CV events.

Corrosion of pipe steels 20 and 17G1S-U in ground electrolytes with a hydrogen indicator close to neutral

Purpose: of this paper is to analyse the mechanism of near-neutral pH corrosion of main gas pipelines. The stages of main gas pipelines in model environments that meet the soil conditions of Ukraine have been studied. Design/methodology/approach: The corrosion rate of steel specimens from steels 17G1S-U and 20 and the influence of borate buffers on their protective properties were evaluated. The influence of corrosion time on changes in pH of model media is shown. Morphological features of surface damages of pipe steels are established. The defect analysis of specimens from steels 17G1S-U and 20 by electron scanning microscopy is carried out. Findings: The effect of borate buffers on the protective properties of the steel grades studied was revealed, and changes in the pH of the model media during corrosion processes were described. The main regularities in corrosion, as well as the surface morphology of damaged specimens, were studied by scanning electron microscopy. Research limitations/implications: Detailed investigation of localised corrosion phenomena induced by inclusions that are present in steels 17G1S-U and 20 is extremely critical. In particular, there is still ambiguity as to whether the localised corrosion initiation induced by non-metallic inclusions is an electrochemical process or a chemical process. Practical implications: The research findings will be used when testing specimens from pipe steels under cyclic loading in the model media studied, as well as for predicting the residual life of gas pipelines with corrosion defects. Their generalization will make it possible to develop the effective methods of ground diagnostics and prediction of SCC of main pipelines. Originality/value: It was found that the corrosion rate is determined by internal (nature and properties of the metal) and external (properties of the aggressive medium and the corrosion process conditions) factors. The protective effect for steel 17G1S in medium NS4 + borate buffer (1: 1) was 61.5%. Steel 20 had the greatest protective effect in medium NS4 + borate buffer (1: 3), which was 87.05%.

Nebivolol is more effective than atenolol for blood pressure variability attenuation and target organ damage prevention in L-NAME hypertensive rats.

β-Adrenergic blockers are no longer recommended as first-line therapy due to the reduced cardioprotection of traditional β-blockers compared with other antihypertensive drugs. It is unknown whether third-generation β-blockers share the limitations of traditional β-blockers. The aim of the present study was to compare the effects of nebivolol or atenolol on central and peripheral systolic blood pressure (SBP) and its variability and target organ damage (TOD) in N-nitro-L-arginine methyl ester (L-NAME) hypertensive rats. Male Wistar rats were treated with L-NAME for 8 weeks together with oral administration of nebivolol 30 mg/kg (n = 8), atenolol 90 mg/kg (n = 8), or vehicle (n = 8). The control group was composed of vehicle-treated Wistar rats. SBP and its variability, as well as echocardiographic parameters, were assessed during the last 2 weeks of treatment. Tissue levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor β (TGF-β), and histopathological parameters were evaluated in the left ventricle and aorta. Nebivolol had a greater ability than atenolol to decrease central SBP and mid-term and short-term blood pressure variability (BPV) in L-NAME rats. Echocardiographic analysis showed that nebivolol was more effective than atenolol on E/A wave ratio normalization. Compared with atenolol treatment, nebivolol had a greater protective effect on different TOD markers, inducing a decrease in collagen deposition and a reduction in the proinflammatory cytokines IL-6 and TNF-α in the left ventricle and aorta. Our findings suggest that the adverse hemodynamic profile and the reduced cardiovascular protection reported with traditional β-blockers must not be carried forward to third-generation β-blockers.

HIGHLIGHTS OF HYPERTENSIVE AND NORMOTENSIVE GLAUCOMA.

The paper presents the up-to-date overview of pathogenesis, functional and structural changes in normotensive glaucoma (NTG) and its differences from hypertensive glaucoma (HTG). The autors point out new facts that distinguish both diagnostic groups. In the first place are the results of OCT angiography, which verify the pathology of NTG to the anterior part of optic nerve. Our findings confirmed that vascular component (VD) is more involved in changes of visual field than in perfusion parameters, especially in arteria ophtalmica (AO). Perfusion in arteria centralis retinae (ACR) does not play asignificant role in NTG changes in the visual field. VD has very little effect on changes in visual field in HTG. Similarly, the retinal nerve fiber layer (RNFL) for changes in the visual field. Howerver, VD is moderately influenced by changes in RNFL. It should be emphasized that we compared the sum of sensitivity in the central part of the visual field (0-22 degrees) with RNFL and VD. In NTG, the anterior part of the optic nerve is altered. Mainly VD contributes to visual filed changes in NTG. It is also important to note that when the intraocular pressure (IOP) increased above 20 mm Hg, the macular and papillary VD was significantly reduced. Antiglaucomatous treatment with prostaglandins and beta-blockers is essential for the reduction of IOP in HTG. This reduction shoud be bellow 20 mm Hg, in eyes with thinner cornea the decrease in IOP should be more pronounced. It does not matter which antiglaucoma treatment was used. However, it should be noted that prostaglandins have agreater effect on disease progression, but the greater protective effect on the visual field have beta-blockers. Neuroprotectives should be recommended systemically in patients with HTG. When treating NTG, it is important to maintain blood flow of the posterior pole of the eye, but mainly of the anterior part of the optic nerve. Prostaglandins are not suitable in NTG patients, although their effect on IOL reduction is high. Beta-blockers (betaxolol and carteol) and brimonidine are most suitable. Corneal thickness has no effect on disease progression.

Investigation of color and anticorrosive properties of pigments in the Fe-Al-Mg-O-H system by the simplex lattice method

PurposeThe purpose of this paper is to study the patterns of formation of anti-corrosion properties, the development of compositions for pigments by using the method of co-precipitation and subsequent heat treatment.Design/methodology/approachTo obtain co-precipitated hydroxides, aqueous solutions of salts were used. The conditions of synthesis varied according to the following parameters: the nature of the starting salts of metals; and the ratio of metal cations. The anticorrosive activity of the pigments was evaluated by the potentiodynamic method, by comparing the anodic and cathodic polarization curves, and calculated potentials and corrosion currents on the basis of regions of Tafel on curves. Polarization curves were obtained by using Potentiostat/Galvanostat/ZRA Gamry, which connected to the PC, and by using the program Gamry Framework. The measurement results were processed by using the method of simplex-lattice planning. X-ray diffractograms of pigments were recorded on a DRON – 2.0 diffractometer (monochromatic copper radiation with a nickel filter).FindingsThe paper deals with the results of research the dependence of colour characteristics and anticorrosion properties of synthesized compositions on their nature and composition. The presence of aluminium cations leads to the formation of solid solutions of ferrum and aluminium oxyhydroxides.Originality/valueThe main technological properties of pigments are determined by the anionic and cationic composition. Colour characteristics are determined by the cation-chromophore. The anti-corrosive properties of non-calcined pigments are determined to a greater extent by the presence of the formed hydroxyl ions and the composition of the compounds. The greatest protective effect is observed when using double compounds of metals, the dissociation constants of which differ significantly. The protective effect is mainly determined by the slowdown of the anode process. Anions containing aluminium atoms accelerate the corrosion processes.

Non-ionic surfactant vesicles as a carrier system for dermal delivery of (+)-Catechin and their antioxidant effects

Numerous skin disorders and diseases are related to oxidative stress. The application of an antioxidant, serving as a strong defense agent against oxidation, is of great interest in dermatology yet remains challenging for delivery. This paper aimed to develop a niosome carrier system to deliver the antioxidant (+) Catechin into the skin. (+) Catechin-loaded niosomes were prepared using film hydration technique and the physicochemical properties of drug-loaded niosomes were characterised and investigated by a series of in vitro and ex vivo studies. The optimised formulation displayed an acceptable size in nanoscale (204 nm), high drug entrapment efficiency (49%) and amorphous state of drug in niosomes. It was found that (+) Catechin-loaded niosomes could effectively prolong the drug release. Drug deposition in the viable layers of human skin was significantly enhanced when niosomal carriers were applied (p < 0.05). Compared to the pure drug, the niosomal formulation had a greater protective effect on the human skin fibroblasts (Fbs). This is consistent with the observation of internalisation of niosomes by Fbs which was concentration-, time- and temperature-dependent, via an energy-dependent process of endocytosis. The research highlighted that niosomes are potential topical carriers for dermal delivery of antioxidants in skin-care and pharmaceutical products.

EXPLORING NOVEL EFFECTS OF STATINS ON SEPSIS MORTALITY WITHIN A REAL-WORLD SETTING

SESSION TITLE: Diagnostic and Prognostic Insights into Sepsis SESSION TYPE: Original Investigations PRESENTED ON: October 18-21, 2020 PURPOSE: Statins have been suggested to attenuate the severity of sepsis. They have demonstrated antimicrobial properties both in vivo and in vitro. Fungal-derived statins may accomplish this due to their similarities to penicillin. Another mechanism may be related to statins’ lipophilic properties, disrupting lipid membranes resulting in cell death. The pleiotropy of effects including anti-inflammatory, immunomodulatory, and anti-cancer properties have been well characterized. We compared mortality outcomes in statin users versus non-users within a real world setting of Kaiser Permanente Southern California (KPSC). Additionally, mortality was compared among statin users based on fungal versus synthetic-derived and lipophilic versus hydrophilic statins. METHODS: A retrospective cohort study of patients admitted to hospitals within the KPSC health care system admitted for sepsis in the period 1/1/2008-9/30/2018. Sepsis was identified based on the International Classification of Diseases coding. Use of statin was defined as individuals who had filled at least two prescriptions for a statin. Short-term mortality in septic patients was analyzed among comparison groups: statin versus non-statin, hydrophilic versus lipophilic, and fungal versus synthetic derivation. For univariate analysis of categorical variables, we used Pearson chi-square test. For continuous variables, we used Wilcoxon rank-sum test. Multivariable Cox regression models were used to estimate hazard ratios (HR) 30 and 90-day mortality with adjustment for age, race, sex, and comorbidities determined as risk factors for sepsis. All statistical analyses were performed using SAS EG version 7.1 (SAS Institute, Cary, NC USA). P-value <0.05 was considered statistically significant. RESULTS: 137,019 patients were included, of which 36,908 were taking statins. With non-statin users as reference, differences in the 30-day and 90-day mortality HR’s (95% CI) for statin users were 0.79; (0.77-0.82) and 0.79; (0.77-0.81), respectively. Lipophilic compared to hydrophilic statin users had a 30-day and 90-day mortality HR of 1.13; (1.02-1.26) and 1.17; (1.07-1.28), respectively. Fungal derived statins compared to synthetic derived statin users had a 30-day and 90-day mortality HR of 1.12; (1.06-1.19) and 1.14; (1.09-1.20), respectively. CONCLUSIONS: In patients admitted with sepsis, we observed that statin users had lower mortality compared to non-statin users. Hydrophilic statins and synthetic statins had lower mortality outcomes than lipophilic and fungal derived statins, respectively. Our findings suggest a potential benefit of statins in patients with sepsis. Furthermore, based on their mechanism, certain statins may have a greater protective effect in the course of sepsis. CLINICAL IMPLICATIONS: For populations who are at greater risk for sepsis (immunocompromised, diabetics, elderly) and require a statin, use of certain statins may be a consideration. DISCLOSURES: No relevant relationships by Michael Gould, source=Web Response No relevant relationships by Brannen Liang, source=Web Response No relevant relationships by John Sim, source=Web Response No relevant relationships by Kenneth Wei, source=Web Response No relevant relationships by Su-Jau Yang, source=Web Response

Efficacy of commercial polyvalent avian infectious bronchitis vaccines against Chinese QX-like and TW-like strain via different vaccination strategies

The infectious bronchitis virus (IBV) is an acute and highly contagious disease, which affects chickens of all ages. Vaccination is the most important way to control this disease. Nevertheless, novel variant strains are constantly reported because of the lack of proofreading capabilities of RNA polymerase and high frequency of homologous RNA recombination. Cross-protection studies has demonstrated that the vaccines could provide great protective effects against viruses of same serotype or genotype. However, the protective effect of different commercial vaccines and vaccine combinations against the prevalent IBV strains in China has rarely been studied. Owing to the multiple genotype or serotype IBV strains prevalence in China, the polyvalent vaccines and their composition were used to expanding the protection spectrum of vaccine in practical application. To evaluate the protection of Chinese commercial IBV polyvalent vaccines against prevalent strains (QX-like and TW I-like), an immune challenge test was conducted. Four polyvalent vaccines, containing 4/91, H120, YX10p90, LDT3-A, and 28/86, were combined to form 8 vaccination strategies, almost all of which could provide more than 70% protection effects against challenge with QX-like strain. Particularly, the best protection rate (93%) was generated by administration the polyvalent vaccine C (H120 + 28/86 + 4/91) at 1 D of age and the polyvalent vaccine B (H120 + 4/91 + YX10p90) at 10 D of age. However, all the vaccination strategies in this study cannot provide great protective effects against TW-like strain, and more vaccines should be included in studies to expand the protection spectrum of vaccine. Therefore, for the newly emerging IBV strains, immunization with polyvalent vaccines via different vaccination strategies could be used to control the prevalence of IBV in a short time, whereas developing the homologous vaccines was not always necessary.

Adaptogenic correction of free radical brain damage in subchronic exposure to sodium fl uoride

Introduction. Fluorine compounds in small doses, but with prolonged exposure, cause various disorders in organs at the cellular and molecular levels. Activation of free-radical processes plays an important role in the damaging eff ect of fl uorides. Th erefore, one of the most eff ective ways to limit fl uorine-induced damage is to directly aff ect free-radical processes using herbal preparations with antioxidant properties.The aim of the study is to study the eff ect of a dihydroquercetin-based drug on the activity of free radical processes in brain tissue under subchronic exposure to sodium fl uoride (NaF).Materials and methods. Th e work was performed on white male laboratory rats weighing 200-250 g. Th e rats were divided into 3 groups: 1 — control; 2 — rats with chronic exposure to sodium fl uoride (NaF) for 9 weeks; 3 — rats receiving a NAF solution with simultaneous administration of a complex drug based on dihydroquercetin at a dose of 3 mg/kg in 1% starch gel for 3, 6 and 9 weeks. The activity of free radical oxidation and antioxidant defense enzymes — superoxide dismutase (SOD) and catalase-was determined in the cerebral cortex. Th e level of expression of hypoxia-induced transcription factor HIF — 1A and inducible forms of proteins HSP72 and HSP32 were determined in the cytosolic fraction of brain tissue.Results. In the early stages of subchronic fl uoride exposure (1-3 weeks), the expression of protective proteins HIF-1α, HSP72, HSP32 and catalase was shown in the rat cortex, as a result of which the activity of free-radical processes was maintained at the control level. An increase in the timing of fl uoride intake to 9 weeks led to a decrease in antioxidant protection and signifi cant activation of free radical oxidation in brain tissue. Daily administration of a complex drug with dihydroquercetin for 3, 6 and 9 weeks to rats with subchronic fl uoride exposure led to a decrease in the severity of pro- and antioxidant balance disorders in the cerebral cortex. At the same time, the greatest protective eff ect of dihydroquercetin with fl uoride exposure was manifested by the 9th week of its administration.Conclusions. When subchronic intake of fl uorides in the body, the drug based on dihydroquercetin has a neuroprotective eff ect, which is manifested by an increase in the activity of antioxidant enzymes of fr ee radical oxidation and catalase and the resistance of the cortex to induced fr ee radical oxidation.

Lycopene Ameliorate the Gentamicin Induced Nephrotoxicity in White Mice Model

Gentamicin is an aminoglycoside antibiotic used against gram-negative bacterial infections. In the face of antibiotics, gentamicin also has a toxic effect on kidney. This study investigated the protective role of lycopene against gentamicin induced nephrotoxicity. Results of this works found that lycopene has a great protective effect on the oxidative status of the kidney challenged with gentamicin and significantly ameliorated (P £ 0.05) the level of oxidative markers MDA, GPx and SOD in kidney cells. Kidney function markers (serum urea and creatinine) were ameliorated by using lycopene in comparison with mice challenged by gentamicin. Results of this work showed that lycopene decreased the pro-inflammatory cytokines (IL-6 and TNF-á) and anti-inflammatory cytokines (IL-4 and IL-10). mRNA expression rate of different investigated cytokine markers were modified significantly (P £ 0.05) in lycopene treated group. Serum glucose also adjusted significantly using lycopene. Oxidative stress results were confirmed by histopathological investigations those showed a protective effect of lycopene of kidney tubules.

Tomato waste extract (Lycopersicon esculentum) as a natural antioxidant in soybean oil under heating

The tomato processing industry generates a large amount of waste, usually composed of peels and seeds. It is known that the tomato is rich in bioactive compounds, mainly carotenoids (lycopene and ?-carotene), however, studies on the functionality of its residues are scarce. Thus, these residues are discarded without the knowledge of possible antioxidant potential. The objective of this work was to determine the stability of bioactive in soybean oil added to the extract of agroindustrial tomato waste under heating. The extract obtained with ethyl alcohol at the ratio of 1: 5 (w/v) was initially analyzed for total phenolic compounds, lycopene, ?-carotene, and antioxidant activity using the DPPH and ?- carotene / linoleic acid. Subsequently, the extract and the synthetic antioxidants, butylhydroxytoluene (BHT) and tert-butylhydroquinone (TBHQ) were applied in soybean oil, and the treatments subjected to heating in Rancimat (180oC/5 h). The thermoxidated samples were analyzed for the composition of tocopherols by high-performance liquid chromatography (HPLC), phytosterols, and fatty acid profile by gas chromatography (GC). The extract of agro-industrial tomato residues showed moderate results concerning its antioxidant activity, 68% by the DPPH method, and 26.2% of auto-oxidation of the ?-carotene / linoleic acid system. The synthetic antioxidant TBHQ had a greater protective effect on soybean oil when compared to the control, providing greater retention of phytosterols (85%) and tocopherols (93%). Tomato extract can be used as a natural antioxidant in industrialized oils, but with less effectiveness than the antioxidant TBHQ.

Potencial antioxidante e estabilidade do bioaditivo de jucá (Libidibia ferrea)

O jucá é uma planta comum no nordeste brasileiro, tem sua capacidade antioxidante conhecida e poder terapêutico comprovado. Porém, existem poucas informações sobre sua utilização como bioaditivo antioxidante em óleo de soja. Desta forma, investigou-se a eficácia antioxidante dos extratos aquosos e hidroalcoólicos do jucá, por meio das análises in vitro (teor de compostos fenólicos totais, atividade antioxidante pelos métodos sequestrador de radical livre - DPPH e por redutor de ferro - FRAP), e in vivo (índice de peróxido do óleo de soja aditivado, monitorado por 90 dias). Os extratos hidroalcoólicos do jucá apresentaram maior estabilidade oxidativa que os extratos aquosos. Os extratos hidroalcoólicos do jucá apresentaram elevados teores de compostos fenólicos (166,59 mgEAG/g de fruto e 179,55 mgEAG/g de casca do caule), e elevadas atividades antioxidantes pelos métodos de DPPH e FRAP, ao final dos 90 dias. As investigações in vivo indicaram que a formulação de extrato hidroalcoólico com 0,85% do fruto e 0,85% da casca do caule apresentaram um maior efeito protetor contra o aumento do índice de peróxido no óleo de soja, mostrando que a utilização simultânea dos aditivos apresenta efeito antioxidante sinérgico. Portanto, os extratos hidroalcoólicos de jucá podem ser utilizados como bioaditivo antioxidante em óleo de soja.

Neuroprotective effect of low-intensity transcranial ultrasound stimulation in endothelin-1-induced middle cerebral artery occlusion in rats

BackgroundIschemic stroke is one of the leading causes of death and disability worldwide. Low-intensity transcranial ultrasound stimulation (LITUS) is a promising neuroprotective treatment for ischemic stroke. Diffusion-weighted imaging (DWI) can be highly sensitive in the detection of ischemic brain injury. Relative apparent diffusion coefficient (rADC) values can be used to evaluate the effect of LITUS on ischemic stroke. PurposeThe aim of this study was to determine the neuroprotective effect of LITUS at different time points using endothelin-1-induced middle cerebral artery occlusion in rats as a model of ischemic stroke. MethodsEndothelin-1 (ET-1) was injected into the cerebral parenchyma near the middle cerebral artery, which induced focal, reversible, low-flow ischemia in rats. After occlusion of the middle cerebral artery for 30 min, 120 min, and 240 min, LITUS stimulation was used respectively. DWI was performed at 1, 3, 6, 12, 18, 24, 48, and 72 h after ischemia using a 3 T scanner. The rADC values were calculated, and functional outcomes assessed using neurobehavioral scores after ischemia. Nissl staining and estimation of Na+–K+-ATPase activity were used to assess the neuropathology after completing the last Magnetic Resonance Imaging (MRI) examination. ResultsEndothelin-1-induced occlusion of the middle cerebral artery resulted in significant dysfunction and neuronal damage in rats. Rats that received LITUS exhibited reduced damage of the affected brain tissue after cerebral ischemia. The greatest protective effect was found when LITUS stimulation occurred 30 min after cerebral ischemia. ConclusionsImaging, behavioral, and histological results suggested that LITUS stimulation after an ischemic stroke produced significant neuroprotective effects.

The underlying mechanisms of lorlatinib penetration across the blood-brain barrier and the distribution characteristics of lorlatinib in the brain.

ObjectiveTo clarify the distribution of lorlatinib in the brain and elucidate the molecular mechanisms of lorlatinib penetration across the blood‐brain barrier (BBB).MethodsCytological experiments were performed to investigate the growth inhibitory effect of lorlatinib on different cells (endothelial cells HUVEC, HMEC‐1, and HCMEC/D3) and to investigate the protective effect of lorlatinib on neuronal cells after SH‐SY5Y hypoxia/reoxygenation injury. Furthermore, rat brain tissue was sequenced, and the differentially expressed genes (secreted phosphoprotein 1 (SPP1), vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF‐β), Claudin, ZO‐1 and P‐gp) in several different drug treatment groups were verified by Real‐Time PCR. Lorlatinib brain distribution was predicted by physiologically based pharmacokinetics (PBPK).ResultsLorlatinib and crizotinib both had inhibitory effects on endothelial cells, however lorlatinib inhibited the growth of HCMEC/D3 more efficaciously than crizotinib. In the SH‐SY5Y hypoxia model, lorlatinib had a greater protective effect on nerve cell damage caused by hypoxia and reoxygenation than crizotinib. The expression of SPP1, VEGF, TGF‐β, and Claudin in brain tissue was significantly downregulated after lorlatinib administration, and the expression level of early growth transcription factor 1 (Egr‐1) was significantly increased. The PBPK model successfully described lorlatinib concentrations in blood and brain tissue in the mouse model and gave a brain tissue partition coefficient of 0.7.ConclusionLorlatinib can increase the permeability of the blood‐brain barrier whereby we suggest its underlying working mechanism is related to downregulating SPP1, inhibiting VEGF, TGF‐β, and Claudin subsequently reducing the number of tight junctions between BBB cells. Lorlatinib plays a protective role on injured nerve cells and does not change the amount of P‐gp expression in brain tissue, which may be important for its ability to be efficacious across the BBB with a low incidence of resistance.

The problem of underdosing with direct-acting oral anticoagulants in elderly patients with nonvalvular atrial fibrillation

Unless contraindicated, anticoagulant therapy should be prescribed to elderly patients with atrial fibrillation. Direct-acting oral anticoagulants (DOACs) are superior to vitamin K antagonists for preventing stroke. This, together with their higher net clinical benefit, makes DOACs the treatment of choice in this population. However, due to the concerns about bleeding and the need for dose adjustment based on clinical variables, underdosing of DOACs is common and the risk of stroke high. Drugs with more easily adjusted doses are likely associated with a lower risk of dosing errors and, therefore, a greater protective effect. Correct dosing can ensure a maximal net benefit of DOACs in elderly patients with atrial fibrillation.

Low serum 25-hydroxyvitamin D status in the pathogenesis of stress fractures in military personnel: An evidenced link to support injury risk management.

Stress fractures are common amongst healthy military recruits and athletes. Reduced vitamin D availability, measured by serum 25-hydroxyvitamin D (25OHD) status, has been associated with stress fracture risk during the 32-week Royal Marines (RM) training programme. A gene-environment interaction study was undertaken to explore this relationship to inform specific injury risk mitigation strategies. Fifty-one males who developed a stress fracture during RM training (n = 9 in weeks 1-15; n = 42 in weeks 16-32) and 141 uninjured controls were genotyped for the vitamin D receptor (VDR) FokI polymorphism. Serum 25OHD was measured at the start, middle and end (weeks 1, 15 and 32) of training. Serum 25OHD concentration increased in controls between weeks 1-15 (61.8±29.1 to 72.6±28.8 nmol/L, p = 0.01). Recruits who fractured did not show this rise and had lower week-15 25OHD concentration (p = 0.01). Higher week-15 25OHD concentration was associated with reduced stress fracture risk (adjusted OR 0.55[0.32-0.96] per 1SD increase, p = 0.04): the greater the increase in 25OHD, the greater the protective effect (p = 0.01). The f-allele was over-represented in fracture cases compared with controls (p<0.05). Baseline 25OHD status interacted with VDR genotype: a higher level was associated with reduced fracture risk in f-allele carriers (adjusted OR 0.39[0.17-0.91], p = 0.01). Improved 25OHD status between weeks 1-15 had a greater protective effect in FF genotype individuals (adjusted OR 0.31[0.12-0.81] vs. 1.78[0.90-3.49], p<0.01). Stress fracture risk in RM recruits is impacted by the interaction of VDR genotype with vitamin D status. This further supports the role of low serum vitamin D concentrations in causing stress fractures, and hence prophylactic vitamin D supplementation as an injury risk mitigation strategy.

Exogenous melatonin mitigates the salinity damages and improves the growth of pistachio under salinity stress

This study investigated the ability of exogenous melatonin (MT) to alleviate salinity stress in pistachio seedlings (Pistacia vera cv. Badami-Zarand) in a controlled greenhouse. Seedlings were treated with different salinity levels (25, 50, and 100 and 150 mM). Foliar application of melatonin with 0, 25, 50, 75, 100, 125 and 150 μmol/L concentrations was applied two times during the seeding treated with the various salinity levels. The results indicated that the deleterious effects of MT application were observed when they were applied under non-stressful conditions (control). The greatest protective effect against simulated salinity stress was observed in 100 μmol/L of MT in 150 mM salinity levels. Melatonins markedly alleviated the inhibitory effects of salinity on root and shoot growth, chlorophyll level and ion leakage. Activities of antioxidant enzymes, proline content, endogenous polyamine and melatonin increased with exogenous application of MT in salinity stress condition. Exogenous melatonin was also associated with significant increases in the nutrient uptake. Therefore, exogenous melatonin can attenuate the salinity damage via enhancing anti-oxidation ability, osmotic activity-adjusting, nutrient uptake and polyamines biosynthesis.

Protective Effects of Tropical Fruit Processing Coproducts on Probiotic Lactobacillus Strains during Freeze-Drying and Storage.

This study evaluated the protective effects of coproducts from agroindustrial processing of the tropical fruits acerola (Malpighia glabra L., ACE), cashew (Anacardium occidentale L., CAS), and guava (Psidium guayaba L., GUA) on the probiotics Lactobacillus paracasei L-10, Lactobacillus casei L-26, and Lactobacillus acidophilus LA-05 during freeze-drying and storage. The occurrence of damage to membrane integrity, membrane potential, and efflux activity of Lactobacillus cells after freeze-drying was evaluated by flow cytometry, and viable counts were measured immediately after freeze-drying and during 90 days of storage under refrigerated or room temperature conditions. Probiotic strains freeze-dried without substrate had the overall highest count reductions (0.5 ± 0.1 to 2.9 ± 0.3 log cycles) after freeze-drying. Probiotics freeze-dried with fruit processing coproducts had small cell subpopulations with damaged efflux activity and membrane potential. Average counts of probiotics freeze-dried with ACE, CAS, or GUA after 90 days of storage under refrigerated or room temperature were in the range of 4.2 ± 0.1 to 5.3 ± 0.2 and 2.6 ± 0.3 to 4.9 ± 0.2 log CFU/g, respectively, which were higher than those observed for strains freeze-dried without substrate. The greatest protective effects on freeze-dried probiotics were overall presented by ACE. These results revealed that ACE, CAS, and GUA can exert protective effects and increase the stability of probiotic lactobacilli during freeze-drying and storage, in addition to supporting a possible added-value destination for these agroindustrial coproducts as vehicles for probiotics and for the development of novel functional foods.

Эффективность микробиологических препаратов на основе Bacillus subtilis и Trichoderma harzianum в защите ярового ячменя от болезней на Северо-Западе России

The efficacy of microbiological plant protection specimens based on Bacillus subtilis (Vitapan, SP) and Trichoderna harzianum (Trikhotsin, SP) was studied on such spring barley diseases as a root rot and Helminthosporium leaf spot. The use of these biological products in the treatment of seeds and vegetative plants of spring barley was ineffective, namely a decrease in the development of root rot and helminthosprium disease did not exceed 35%. A greater protective effect was achieved when using studied preparations for treating seeds with a low degree of infection with the main pathogen of root rot. The use of Vitaplan in a tank mixture with reduced consumption rates of the chemical fungicides was less effective than pure chemicals with full consumption rates: the decrease was 17% for root rot and 12.7% for Helminthosporium leaf spot. Thus, it is advisable to use mixtures of chemicals with the Vitaplan as a biological for treatment of seeds with an average degree of infection by root rot pathogens and a predicted moderate development of Helminthosporium disease. spring barley, biological plantprotecting agents, root rot, protective efficiency.

Direct sensing of peroxynitrite anion at sensitive hollow tubular organic conjugated microporous polymers modified electrode. Application to selective analysis of ROS and RNS in cells

The aberrant expression levels of reactive oxygen and nitrogen species (ROS and RNS) in human cells are related with many diseases, including cancer. In recent years, the primary RNS, peroxynitrite anion (ONOO−), has aroused immense research interest in the biological and biomedical fields. Herein, we build a novel sensing platform by the hollow tubular organic conjugated microporous polymer (HTCMPs) modified glassy carbon electrode (GCE) for directly monitoring of ONOO−. Specifically, the HTCMP was used to develop an electrochemical sensor for the first time. This as-prepared amperometric sensor showed an excellent activity toward the oxidation of ONOO− with a wide range of four orders of magnitude and a super low detection limit reached 1.54 ± 0.5 nM (S/N = 3). With these properties, the sensor was used for measuring the ONOO− released from glioma cells (U87) during oxidative stress induced by biochemical reagent stimulation. For the more, a new strategy to verify antioxidant protection was developed by stimulating cells at low or high doses of stimulus in a vitro simulation environment. The results showed that reduced glutathione (GSH) had great protective effect on cells in the case of oxidative stress. Last but not least, based on a battery of control tests, the concentrations of two key ROS/RNS (H2O2, ONOO−) in the cells were determined. This study essentially offers a reproducible platform for assessing the oxidative stress metabolites (ROS/RNS) in a vivo assays.