Interactions Between the Glutamate and Glycine Recognition Sites of the N-Methyl-d-Aspartate Receptor from Rat Brain, as Revealed from Radioligand Binding Studies

Abstract: The N-methyl-d -aspartate (NMDA) receptor possesses two distinct amino acid recognition sites, one for glutamate and one for glycine, which appear to be allosterically linked. Using rat cortex/hippocampus P₂ membranes we have investigated the effect of glutamate recognition site ligands on [³H]glycine (agonist) and (±)4-trans-2-car-boxy-5,7-dichloro-4-[³H]phenylaminocarbonylamino-1,2,3,4-tetrahydroquinoline ([³H]l -689,560; antagonist) binding to the glycine site and the effect of glycine recognition site ligands on l -[³H]glutamate (agonist), dl -3-(2-carboxypiperazin-4-yl)-[³H]propyl-1 -phosphonate ([³H]-CPP; “C-7” antagonist), and cis-4-phosphonomethyl-2-[³H]piperidine carboxylate ([³H]CGS-19755; “C-5” antagonist) binding to the glutamate site. “C-7” glutamate site antagonists partially inhibited [³H]l -689,560 binding but had no effect on [³H]glycine binding, whereas “C-5” antagonists partially inhibited the binding of both radioligands. Glycine, d -serine, and d -cycloserine partially inhibited [³H]CGS-19755 binding but had little effect on l -[³H]-glutamate or [³H]CPP binding, whereas the partial agonists (+)-3-amino-1-hydroxypyrrolid-2-one [(+)-HA-966], 3R-(+)cis-4-methyl-HA-966 (l -687,414), and 1-amino-1-carboxycyclobutane all enhanced [³H]CPP binding but had no effect on [³H]CGS-19755 binding, and (+)-HA-966 and l -687,414 inhibited l -[³H]glutamate binding. The association and dissociation rates of [³H]l -689,560 binding were decreased by CPP and d -2-amino-5-phosphonopentanoic acid (“C-5”). Saturation analysis of [³H]l -689,560 binding carried out at equilibrium showed that CPP had little effect on the affinity or number of [³H]l -689,560 binding sites. These results indicate that complex interactions occur between the glutamate and glycine recognition sites on the NMDA receptor. In addition, mechanisms other than allosterism may underlie some effects, and the possibility of a steric interaction between CPP and [³H]l -689,560 is discussed.     

Does Gγ/Aγ ratio and Hb F level influence the severity of sickle cell anaemia

Sickle cell anaemia (SCA) exhibits significant variations in clinical presentation in different populations for which several genetic factors including SCA-associated -and -thalassaemias, G-6-PD deficiency and elevated Hb F level have been implicated as possible ameliorating factors. Saudi Arabia is unique in that mild and severe forms of the disease occur at a high frequency. We investigated the G/A ratio and Hb F level and correlated these values with the severity of SCA. The results showed that Hb F level varies significantly in both groups of patients with no evident correlation with the mild clinical manifestations. However, G/A ratio correlated significantly with the disease severity where a high ratio was observed in patients with the mild and a low ratio in patients with the severe disease. The results are evaluated and discussed in the light of correlation studies and regression analysis.     

Ethical obligation and legal requirements: On informed consent practices in Bangladesh

Informed consent to medical intervention is fundamental in both ethics and law. But in practice it is often not taken seriously in developing countries. This paper provides an appraisal of informed consent practices in Bangladesh. Following a review of the ethical and legal principles of informed consent, it assesses the degree to which doctors adhere to it in Bangladesh. Based on findings of non-compliance, it then investigates the reasons for such non-compliance through an appraisal of informed consent practices in Bangladesh and provides recommendations aimed at improving such practices. The significance of this paper lies in unveiling the interdependence between the ethical and legal traits of informed consent and their ramifications on strengthening the patient-oriented approach of duty to care.     

Flow injection assays for NADH and ethanol using photosensitized rose bengal and luminol–copper (II) chemiluminescence system

The online photoreaction of the rose bengal photosensitized luminol–copper (II) chemiluminescence (CL) system was used for the determination of β-nicotinamide adenine dinucleotide (NADH) and ethanol (EtOH) in pharmaceutical formulations combined with a flow injection technique. NADH can significantly enhance the CL emission of the reaction. For EtOH, alcohol dehydrogenase in soluble form was utilized in the presence of nicotinamide adenine dinucleotide resulting in NADH production. The limit of detection (3σ blank, 𝑛 = 3) of 4.0 × 10⁻⁸ and 2.17 × 10⁻⁵ M, and linear range 1.3 × 10⁻⁷ to 2.5 × 10⁻⁵ M (R² = 0.9998, n = 6) and 0.11–2.17 × 10⁻³ M (R² = 0.9996, n = 6) were obtained for NADH and EtOH respectively. The injection rate was 100 h⁻¹ with a relative standard deviation (n = 3) of 1.5–4.8% in the range studied for both analytes. The procedure was satisfactorily applied to pharmaceutical formulations with recoveries in the range 91.6 ± 3.0% to 110 ± 2.0% for NADH and 88 ± 3.0% to 95.4 ± 4.0% for EtOH. The results obtained were very consistent and did not differ considerably from the reported approaches at a 95% confidence limit. The possible mechanism of the CL reaction is also explained briefly.     

Improvement of Early Maturing and Climate Resilient Chickpea (<i>Cicer arietinum</i> L.) Cultivars Suitable for Multiple Environments in Bangladesh

Ensuring food security for the rapidly increasing population and changing climatic scenarios are requisites for exploiting the genetic divergence of food crops. A study was undertaken to sort out an early maturing chickpea variety for fitting easily between rice-rice cropping systems in the Eastern Indo-Gangetic Plain of Bangladesh. The trial was comprised of eight elite lines of chickpea and executed at various localities in Bangladesh from 2014– 15 to 2017–18. The result explored the chickpea genotype, BARI Chola-11 remained superior to the rest of the elite genotypes for having a short maturity period (100–106 days), and lesser days to 50% flowering (47– 55 days). The same genotype was recorded to have robust vegetative and reproductive yield attributes including plant height (49–57 cm), podsplant⁻¹ (37–50), and optimum 100 seed weight (19.5–20.6 g). Owing to better yield attributes, BARI Chola-11 resulted in the maximum seed yield (1200–1500 kg ha⁻¹ ) of chickpea and might be recommended for general adoption in the region for boosting nutritional security status through improved productivity under changing climate.     

Lipid Production,Oxidative Status,Antioxidant Enzymes and Photosynthetic Efficiency of <i>Coccomyxa chodatii</i> SAG 216-2 in Response to Calcium Oxide Nanoparticles

The extensive use of nanoparticles (NPs) in diverse applications causes their localization to aquatic habitats, affecting the metabolic products of primary producers in aquatic ecosystems, such as algae. Synthesized calcium oxide nanoparticles (CaO NPs) are of the scarcely studied NPs. Thus, the current work proposed that the exposure to CaO NPs may instigate metabolic pathway to be higher than that of normally growing algae, and positively stimulate algal biomass. In this respect, this research was undertaken to study the exposure effect of CaO NPs (0, 20, 40, 60, 80, and 100 µg mL⁻¹ ) on the growth, photosynthesis, respiration, oxidative stress, antioxidants, and lipid production of the microalga Coccomyxa chodatii SAG 216-2. The results showed that the algal growth concomitant with chlorophyll content, photosynthesis, and calcium content increased in response to CaO NPs. The contents of biomolecules such as proteins, amino acids, and carbohydrates were also promoted by CaO NPs with variant degrees. Furthermore, lipid production was enhanced by the applied nanoparticles. CaO NPs induced the accumulation of hydrogen peroxide, while lipid peroxidation was reduced, revealing no oxidative behavior of the applied nanoparticles on alga. Also, CaO NPs have a triggering effect on the antioxidant enzymes such as superoxide dismutase, catalase, ascorbate peroxidase, and guaiacol peroxidase. The results recommended the importance of the level of 60 µg mL⁻¹ CaO NPs on lipid production (with increasing percentage of 65% compared to control) and the highest dry matter acquisition of C. chodatii. This study recommended the feasibility of an integrated treatment strategy of CaO NPs in augmenting biomass, metabolic up-regulations, and lipid accumulation in C. chodatii.     

Anticancer potential of Ferula assa-foetida and its constituents,a powerful plant for cancer therapy

Cancer is one of the main challenges of the health system around the world. This disease is increasing in developing countries and imposes heavy costs on patients and governments. On the other hand, despite various drugs, the death rate among cancer patients is still high and the current treatments have many harmful effects. In the traditional medicine of different countries, there are many medicinal plants that can be effective in the treatment of cancer. Ferula plants are traditionally used as spices and food or for medicinal purposes. Ferula assa-foetida is one of the famous plants of this genus, which has been used for the treatment of various diseases since ancient times. Among the main compounds of this plant, we can mention monoterpenes, sulfide compounds and polyphenols, which can show different therapeutic effects. This article has been compiled with the aim of collecting evidence and articles related to the anti-cancer effects of extracts, derived compounds, essential oils and nanoparticles containing Ferula assa-foetida. This review article was prepared by searching the terms Ferula assa-foetida and cancer, and relevant information was collected through searching electronic databases such as ISI Web of Knowledge, PubMed, and Google Scholar. Fortunately, the results of this review showed that relatively comprehensive studies have been conducted in this field and shown that Ferula assa-foetida can be very promising in the treatment of cancer.     

Design,Synthesis, and Biological Evaluation of Novel Indanone Derivatives as Cholinesterase Inhibitors for Potential Use in Alzheimer's Disease

Indanone derivatives containing meta/para-substituted aminopropoxy benzyl/benzylidene moieties were designed based on the structures of donepezil and ebselen analogs as the cholinesterase inhibitors. The designed compounds were synthesized and their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were measured. Inhibitory potencies (IC₅₀ values) for the synthesized compounds ranged from 0.12 to 11.92 μM and 0.04 to 24.36 μM against AChE and BChE, respectively. Compound 5 c showed the highest AChE inhibitory potency with IC₅₀ value of 0.12 μM, whereas the highest BChE inhibition was achieved by structure 7 b (IC₅₀=0.04 μM). Structure-activity relationship (SAR) analysis revealed that there is no significant difference between meta and para-substituted derivatives in AChE and BChE inhibition. However, the most potent AChE inhibitor 5 c belongs to meta-substituted compounds, while the most active BChE inhibitor is para-substituted derivative 7 b . The order of enzyme inhibition potency based on the substituted amine group is dimethyl amine>piperidine>morpholine. Compounds containing C=C linkage are more potent AChE inhibitors than the corresponding saturated structures. Molecular docking studies indicated that 5 c interacts with AChE in a very similar way to that observed experimentally for donepezil. The introduced indanone-aminopropoxy benzylidenes could be used in drug-discovery against Alzheimer's disease.     

Unveiling the Anthelminthic Potential of Merremia vitifolia Stem through in Vitro and in Silico Approach

This study aimed to assess the anthelmintic activity of methanol extracts from Merremia vitifolia stems using a combination approach encompassing experimental, in vitro, and in silico evaluations. Despite the well-recognized pharmacological properties of M. vitifolia, its potential as an anthelmintic agent remained unexplored. This plant's anthelmintic potential was assessed on adult earthworms (Pheretima posthuma), revealing a dose-dependent reduction in spontaneous motility leading to paralysis and eventual mortality. The most effective dose of M. vitifolia (200 mg/ml) for anthelmintic effects on Pheretima posthuma was identified. Complementary in silico investigations were also conducted, employing Autodock PyRx 0.8 for docking studies of reported M. vitifolia compounds. Notably, quercetin emerged as a promising candidate with superior binding energies against β-tubulin (−8.3 Kcal/mol). Moreover, this comprehensive research underlines the anthelmintic potential of Merremia vitifolia stem extract and highlights quercetin as a noteworthy compound for further investigation in the quest for novel anthelmintic agents.