Oleic acid ameliorates amyloidosis in cellular and mouse models of Alzheimer's disease

Several lines of evidence support protective as well as deleterious effects of oleic acid (OA) on Alzheimer's disease (AD) and other neurological disorders; however, the bases of these effects are unclear. Our investigation demonstrates that amyloid precursor protein (APP) 695 transfected Cos-7 cells supplemented with OA have reduced secreted amyloid-beta (Aβ) levels. An early-onset AD transgenic mouse model expressing the double-mutant form of human APP, Swedish (K670N/M671L) and Indiana (V717F), corroborated our in vitro findings when they were fed a high-protein, low-fat (18% reduction), cholesterol-free diet enriched with OA. These mice exhibited an increase in Aβ40/Aβ42 ratio, reduced levels of beta-site APP cleaving enzyme (BACE) and reduced presenilin levels along with reduced amyloid plaques in the brain. The decrease in BACE levels was accompanied by increased levels of a non-amyloidogenic soluble form of APP (sAPPα). Furthermore, the low-fat/+OA diet resulted in an augmentation of insulin-degrading enzyme and insulin-like growth factor-II. These results suggest that OA supplementation and cholesterol intake restriction in a mouse model of AD reduce AD-type neuropathology.     

Phospholipids and a phospholipid-rich diet alter the in vitro amyloid-beta peptide levels and amyloid-beta 42/40 ratios

Amyloid-β peptides (Aβ) generated by proteolysis of the β-amyloid precursor protein (APP) by β- and γ-secretases play an important role in the pathogenesis of Alzheimer's disease (AD). There is mounting evidence that the lipid matrix of neuronal cell membranes plays an important role in the accumulation of Aβ peptides into senile plaques, one of the hallmarks of AD. With the aim to clarify the molecular basis of the interaction between Aβ and cellular membranes, we investigated the effects of various phospholipids (PLs) and a PL-rich diet on Aβ production. Here we show that modulation of Aβ production and Aβ42:40 ratio is not limited to individual fatty acids, rather it is the composition of the PLs of the membrane bilayer, that influences the specificity and level of the regulated intramembranous proteolysis of APP by the γ-secretase complex. We show that Aβ levels in the conditioned media, in response to some of the PL supplements, is increased in the center and decreased on either side of a graph that resembles bell-shaped distribution. This means that the PLs have less of a tendency to produce unusually extreme effects on Aβ production in SP-C99 transfected Cos-7 cultured cells. We proposed a mechanism-based hypothesis to rationalize PLs’ effects on Aβ production.     

Associations among q-space MRI, diffusion-weighted MRI and histopathological parameters in meningiomas

Objectives

The purposes of this MR-based study were to calculate q-space imaging (QSI)–derived mean displacement (MDP) in meningiomas, to evaluate the correlation of MDP values with apparent diffusion coefficient (ADC) and to investigate the relationships among these diffusion parameters, tumour cell count (TCC) and MIB-1 labelling index (LI).

Methods

MRI, including QSI and conventional diffusion-weighted imaging (DWI), was performed in 44 meningioma patients (52 lesions). ADC and MDP maps were acquired from post-processing of the data. Quantitative analyses of these maps were performed by applying regions of interest. Pearson correlation coefficients were calculated for ADC and MDP in all lesions and for ADC and TCC, MDP and TCC, ADC and MIB-1 LI, and MDP and MIB-1 LI in 17 patients who underwent subsequent surgery.

Results

ADC and MDP values were found to have a strong correlation: r?=?0.78 (P?=?<0.0001). Both ADC and MDP values had a significant negative association with TCC: r?=?–0.53 (p?=?0.02) and –0.48 (P?=?0.04), respectively. MIB-1 LI was not, however, found to have a significant association with these diffusion parameters.

Conclusion

In meningiomas, both ADC and MDP may be representative of cell density.

Key Points

? Diffusion-weighted MRI offers possibilities to assess the aggressiveness of meningiomas. ? The q-space imaging-derived mean displacement correlates strongly with apparent diffusion coefficients. ? Both diffusion parameters showed a strong negative association with tumour cell counts. ? Derived mean displacement may help assess the aggressiveness of meningiomas preoperatively.     

Etiology of acute viral respiratory infections common in Pakistan: A review

Respiratory infections, especially those of the lower respiratory tract, remain a foremost cause of mortality and morbidity of children greater than 5 years in developing countries including Pakistan. Ignoring these acute‐level infections may lead to complications. Particularly in Pakistan, respiratory infections account for 20% to 30% of all deaths of children. Even though these infections are common, insufficiency of accessible data hinders development of a comprehensive summary of the problem. The purpose of this study was to determine the prevalence rate in various regions of Pakistan and also to recognize the existing viral strains responsible for viral respiratory infections through published data. Respiratory viruses are detected more frequently among rural dwellers in Pakistan. Lower tract infections are found to be more lethal. The associated pathogens comprise respiratory syncytial virus (RSV), human metapneumovirus (HMPV), coronavirus, enterovirus/rhinovirus, influenza virus, parainfluenza virus, adenovirus, and human bocavirus. RSV is more dominant and can be subtyped as RSV‐A and RSV‐B (BA‐9, BA‐10, and BA‐13). Influenza A (H1N1, H5N1, H3N2, and H1N1pdm09) and Influenza B are common among the Pakistani population. Generally, these strains are detected in a seasonal pattern with a high incidence during spring and winter time. The data presented include pneumonia, bronchiolitis, and influenza. This paper aims to emphasise the need for standard methods to record the incidence and etiology of associated pathogens in order to provide effective treatment against viral infections of the respiratory tract and to reduce death rates.     

Recombinant factor VIIa in the management of surgery and acute bleeding episodes in children with haemophilia and high responding inhibitors

The management of acute and surgical bleeding episodes in children with severe factor VIII or IX deficiency who develop high responding inhibitors presents a major therapeutic challenge to clinicians. Recombinant factor VIIa (rVIIa) is an effective, reliable and safe treatment that can be used to treat acute bleeding episodes prior to commencing an immune tolerance programme and to cover surgical procedures until the immune tolerance programme is successful. In a significant minority of patients, immune tolerance therapy is ineffective and an alternative haemostatic agent such as rVIIa is required for life-long treatment. The present study evaluated the use of rVIIa in a paediatric setting. Twelve children, aged 1-16 years, were treated successfully with rVIIa to prevent surgical bleeding in 20 surgical procedures (19 central venous access device insertion or removal, 1 dental extraction). Minor postoperative haematomata developed in 2 out of 20 cases after regular rVIIa therapy had been discontinued and resolved with a short course of rVIIa in both cases. Three children had six life- or limb-threatening bleeding episodes. All bleeding episodes resolved with regular rVIIa treatment although topical fibrin glue was needed in one child with a frenulum tear. One patient required two red cell transfusions for symptomatic anaemia resulting from two separate bleeding episodes. The rVIIa therapy was well tolerated and there was no evidence of treatment-related complications. We conclude that rVIIa is the treatment of choice for the management of surgery and acute life- or limb-threatening bleeding in children with haemophilia and high responding inhibitors.     

Experimental and theoretical insights into the corrosion inhibition activity of novel Schiff bases for aluminum alloy in acidic medium

Three novel Schiff bases, namely N-(4-((4-((phenylimino)methyl)phenoxy)methoxy)benzylidene)benzenamine (UA), N-(3-methoxy-4-((2-methoxy-4-((phenylimino)methyl)phenoxy)methoxy)benzylidene)benzenamine (UB), and N-(3-ethyl-4-((2-ethyl-4-((phenylimino)methyl)phenoxy)methoxy)benzylidene)benzenamine (UC), were synthesized and their structures were elucidated through diverse spectroscopic techniques such as FT-IR, GC-MS, ¹H NMR and ¹³C NMR. The corrosion inhibition effect of these Schiff bases on aluminum alloy AA2219-T6 in acidic medium was explored using weight loss, Tafel polarization, and electrochemical impedance spectroscopy. Theoretical quantum chemical calculations using density functional theory were employed to determine the adsorption site. It was found that inhibition efficiencies increase with an increase in the inhibitor concentration. Tafel plots showed that these Schiff bases function as mixed inhibitors. Adsorption of the Schiff bases on aluminum followed the Langmuir adsorption isotherm and the value of showed a dominant chemical mechanism. FT-IR and SEM techniques were used to investigate the surface morphology. The compounds showed a substantial corrosion inhibition for aluminum alloy in 0.1 M HCl at 298 K. UB and UC exhibited superior anticorrosion efficiency compared to UA originating from the electron-donating methoxy and ethoxy group substitutions, respectively. There was found to be good correlation between molecular structure and inhibition efficiencies.

Novel Schiff bases characterized through spectroscopic techniques and used as anticorrosive agents for aluminium alloy acidic medium. Electrochemical techniques and DFT studies were used to study inhibition effect and molecular interactions.     

Scabies in urban Bangladesh

As a part of a larger project on hygiene education and diarrhoeal diseases we followed 766 children less than 6 years of age from October 1984 to September 1985 in Dhaka, Bangladesh. The aims were to estimate the annual risk of infestation with scabies in children, to describe its involvement of other family members, and to determine some of the familial and individual risk factors for apparent infestation by scabies. During this period 589 (77%) children appeared to have been infected with scabies, and 125 (16%) children were infested for more than 6 months. Of the factors examined, direct and indirect indicators of decreased wealth and incorrect hygiene practices correlated with higher rates of apparent infestation, although scabies rates remained high at all socioeconomic levels.