Investigating partitioning of free versus macrocycle bound guest into a model POPC lipid bilayer

We report on the permeation of free and macrocycle-bound avobenzone across a POPC lipid bilayer through combined neutron reflectometry experiments and molecular dynamics simulations. Results indicate that the p-phosphonated calix[8]arene macrocycle limits the avobenzone penetration into the upper leaflet of the membrane. Hence, it could serve as a useful vehicle for safer formulations.

We report on the permeation of free and macrocycle-bound avobenzone across a POPC lipid bilayer through combined neutron reflectometry experiments and molecular dynamics simulations.     

Eulophia Nuda: A Review of Its Traditional Uses,Phytochemistry and Pharmacology

Pharmaceutical Chemistry Journal - Eulophia nuda Lindl. (Orchidaceae) is a small perennial terrestrial herb found in central and Southeast Asian regions usually known for its ethnomedicinal uses by...     

Melatonin attenuates radiation-induced learning deficit and brain oxidative stress in mice

Oxidative stress has been implicated in cognitive impairment in both experimental animals and humans. This implication has led to the notion that antioxidant defence mechanisms in the brain are not sufficient to prevent oxidative damage, and that dietary intake of a variety of antioxidants might be beneficial for preserving brain function. The present study, therefore, aimed to investigate the protective effect of melatonin against radiation-induced impairment in the learning ability of mice. Twenty days oral administration of melatonin (0.1 mg/kg b.w.), followed by an acute exposure to T-radiation (6 Gy), inhibited the radiation-induced decline in learning ability. Biochemical estimation of brain protein carbonyls, malondialdehide (MDA) and reduced glutathione (GSH) in these mice indicated that radiation-induced augmentation of protein oxidation and lipid peroxidation had been significantly ameliorated in melatonin treated, irradiated mice. Radiation-induced deficit of glutathione was also normalized by melatonin administration, as there was no statistical difference from normal at P < 0.001. Results indicate the antioxidative as well as neuroprotective properties ofmelatonin against the radiation. These findings support results showing melatonin as a free radical scavenger.     

Neuroticism and brain responses to anticipatory fear

Personality is known to influence cognitive and affective functioning as well as the risk of psychiatric disorders. Exploration of the neurobiological correlates of personality traits has the potential to enhance understanding of their significance in development of related psychopathological states. The authors examined the association between individual differences in neuroticism and brain activity in response to threat of electric shocks. Fourteen right-handed healthy men underwent functional MRI during a 5-min experiment that involved repeated presentations of two 30-s alternating conditions. In 1 of these conditions, subjects were told to expect mild but painful electric shocks; there was no possibility of receiving shocks in the other condition. The results revealed that neuroticism correlated positively with the ratings of fear of shock and negatively (indicating suppression) with brain activity from safe to shock conditions in the anterior and posterior cingulate, superior/middle temporal gyrus extending to the hippocampus, precuneus, putamen, thalamus, and middle occipital gyrus. The observations support recent psychophysiological research that has demonstrated reduced processing of pain in subjects with higher levels of neuroticism, especially the anxiety component of this trait.     

The effects of ‘activating’ almonds on consumer acceptance and gastrointestinal tolerance

Purpose

Recommendations to soak nuts prior to consumption to reduce phytate concentrations and improve gastrointestinal tolerance have received much attention in the popular press. This is despite no supporting scientific evidence for the practice. There is also a lack of information about how soaking nuts might affect consumer acceptability. This study primarily assessed the effects of soaking almonds on consumer acceptance and secondly assessed effects on gastrointestinal tolerance.

Methods

In this 8-week randomised crossover trial, 76 participants were allocated in balanced order to receive 30 g/day of four different preparations of almonds for 12 days: whole unsoaked, whole soaked, sliced unsoaked, and sliced soaked. Ratings of overall liking, desire to consume, and likelihood of future consumption, and severity of gastrointestinal symptoms were measured daily on visual analogue scales. The phytate concentrations were measured in all four nut types using high-performance liquid chromatography.

Results

Mean acceptance ratings of all nut types were above the neutral point indicating they were acceptable. However, sliced soaked almonds were rated significantly lower overall for all three acceptance scales compared to the other treatments (all P ≤ 0.003). The sliced unsoaked almonds were rated lower than both whole nut treatments (all P ≤ 0.006), while there were no significant differences between the two whole nut treatments (all P ≥ 0.511). Gastrointestinal symptoms were minimal, but flatulence was rated significantly higher for all time points combined for soaked whole nuts compared to unsoaked whole nuts (P = 0.005). Compared to the whole unsoaked nuts (mean [SD] 531 [9] mg/100 g), phytate concentration was higher for the whole soaked almonds (563 [38] mg/100 g, P = 0.016), with no evidence of a difference for the sliced soaked almonds (548 [27] mg/100 g, P = 0.197) and no difference between the soaked forms (P = 0.262).

Conclusions

This research supports previous results suggesting nuts, including different forms, are an acceptable food. They are also well tolerated gastrointestinally, but soaking does not improve gastrointestinal tolerance or acceptance as claimed in the lay literature.

     

Lapatinib nano-delivery systems: a promising future for breast cancer treatment

Introduction: Breast cancer stands the second prominent cause of death among women. For its efficient treatment, Lapatinib (LAPA) was developed as a selective tyrosine kinase inhibitor of receptors, overexpressed by breast cancer cells. Various explored delivery strategies for LAPA indicated its controlled release with enhanced aqueous solubility, improved bioavailability, decreased plasma protein binding, reduced dose and toxicity to the other organs with maximized clinical efficacy, compared to its marketed tablet formulation.

Areas covered: This comprehensive review deals with the survey, performed through different electronic databases, regarding various challenges and their solutions attained by fabricating delivery systems like nanoparticles, micelle, nanocapsules, nanochannels, and liposomes. It also covers the synthesis of novel LAPA-conjugates for diagnostic purpose.

Expert opinion: Unfortunately, clinical use of LAPA is restricted because of its extensive albumin binding capacity, poor oral bioavailability, and poor aqueous solubility. LAPA is marketed as the oral tablet only. Therefore, it becomes imperative to formulate alternate efficient multiparticulate or nano-delivery systems for administration through non-oral routes, for active/passive targeting, and to scale-up by pharmaceutical scientists followed by their clinical trials by clinical experts. LAPA combinations with capecitabine and letrozole should also be tried for breast cancer treatment.     

Evaluation of aqueous extract of Murraya koenigii in unilateral renal ischemia reperfusion injury in rats

Aim:

The aqueous extract of leaves of Murraya koenigii was studied for its renoprotective potential against unilateral renal ischemia reperfusion (RIR) injury in male Wistar rats.

Materials and Methods:

Healthy adult male Wistar rats were divided into five groups (n = 8) and were treated with 200 mg/kg., p.o. of aqueous extract of M. koenigii (AEMK) for 30 days to assess both preventive and curative effects of AEMK. Except Group I, RIR was induced to all the groups by clamping the left renal artery using artery clamp for 1 h followed by reperfusion by removing the clamp. Groups II and III underwent RIR at 30^th day whereas RIR was induced in Groups IV and V at 1^st day of treatment schedule. Biochemical parameters (serum creatinine, blood urea nitrogen, serum total protein and serum Na⁺), urinary parameters (urine output, urinary creatinine, urinary urea, urinary total protein, urinary Na⁺), in vivo anti-oxidants, renal myeloperoxidase (MPO) activity and histopathology of kidneys were monitored. Statistical significance was set at P < 0.05.

Results:

Rats were treated with AEMK significantly (P < 0.05) restored the serum and urinary parameters with significant (P < 0.05) improvement in endogenous anti-oxidants such as superoxide dismutase, catalase and reduced glutathione and decreased levels of malondialdehyde and renal MPO when compared with the control groups. Histopathological examination also supported the biochemical and urinary tests.

Conclusions:

Aqueous extract of M. koenigii possesses both preventive and curative effects against RIR injury.KEY WORDS: Aqueous extract, ischemia reperfusion injury, kidney, Murraya koenigii