Teratogenic effects of dilantin on thoraco-abdominal organs of developing chick embryos

Congenital anomalies on some viscera like heart, liver and kidney have been investigated in chick embryos after a single injection of dilantin (3 mg/egg), a known antiepileptic drug, on 4th day of incubation. On 19th day of incubation, chick embryos were collected to observe the gross malformations and histological changes in heart, liver and kidney. On gross examination, visceroptosis (29%), thin anterior abdominal wall (28%), ectopia cordis (10%) and dextrocardia (1%) were observed. Histological examination of the kidney revealed glomerular degeneration in kidney while in liver, dilated central veins with degenerated hepatocytes were present. Longitudinal section of the heart showed thicker musculature specially of ventricles with a narrower lumen in comparison to that of the control. The results indicate teratogenicity of dilantin in developing chick embryos.     

Promising applications of cold plasma for microbial safety,chemical decontamination and quality enhancement in fruits

Consumers’ demand is increasing for safe foods without impairing the phytochemical and sensory quality. In turn, it has increased research interest in the exploration of innovative food processing technologies. Cold plasma technology is getting popularity now days owing to its high efficacy in decontamination of microbes in fruit and fruit-based products. As a on-thermal approach, plasma processing maintains the quality of fruits and minimizes the thermal effects on nutritional properties. Cold plasma is also exploited for inactivating enzymes and degrading pesticides as both are directly related with quality loss and presently are most important concerns in fresh produce industry. The present review covers the influence of cold plasma technology on reducing microbial risks and enhancing the quality attributes in fruits.     

Interaction of drought and high temperature on photosynthesis and grain-filling of wheat

Drought and high temperature often occur simultaneously, but their effects on crops are usually investigated individually. Our objective was to compare effects of drought, high temperature, and their interactions on photosynthesis and grain-growth of wheat (Triticum aestivum L.). Plants (cv. Len) were grown uniformly in well-watered soil at 25/20 ± 2 °C day/night until anthesis, when they were subjected to regimes of no drought (soil at field capacity) and drought (plant water potential of –.0 to –2.4 MPa) at 15/10, 25/20, and 35/30 °C in controlled environments until physiological maturity. Drought decreased photosynthesis, stomatal conductance, viable leaf area, shoot and grain mass, and weight and soluble sugar content of kernels but increased plant water-use efficiency. High temperature hastened the decline in photosynthesis and leaf area, decreased shoot and grain mass as well as weight and sugar content of kernels, and reduced water-use efficiency. Interactions between the two stresses were pronounced, and consequences of drought on all physiological parameters were more severe at high temperature than low temperature. The synergistic interactions indicated that productivity of wheat is reduced considerably more by the combined stresses than by either stress alone, and that much of the effect is on photosynthetic processes.     

Fluctuations in human serum lipoproteins during the normal menstrual cycle

1. Lipoproteins were measured in sera from 11 young women having a similar environment and diet. Sera were obtained at weekly intervals over a 12-week period. The values of the lipoproteins during periods in the normal ovulatory cycle were compared to assess their relation to reported hormone concentrations in blood. 2. Only the 4–0s_f (HDL₂) (d 1·125 sodium chloride) fraction changed significantly; it increased at ovulation in ten of the 11 subjects and fell as menstruation approached. 3. There was greater variability in most of the low-density rather than the high-density lipoproteins within individuals. The lipoprotein class most characteristic for an individual was the 4–0s_f or HDL₂ fraction.     

Quinazolinones as γ-secretase modulators

Synthesis, SAR and evaluation of styrenyl quinazolinones as novel gamma secretase modulators are presented in this communication. Starting from literature and in-house leads we evaluated a range of quinazolinones which showed good modulation of γ-secretase activity.     

Effects of arginine on heat-induced aggregation of concentrated protein solutions

Arginine is one of the commonly used additives to enhance refolding yield of proteins, to suppress aggregation of proteins, and to increase solubility of proteins, and yet the molecular interactions that contribute to the role of arginine are unclear. Here, we present experiments, using bovine serum albumin (BSA), lysozyme (LYZ), and β-lactoglobulin (BLG) as model proteins, to show that arginine can enhance heat-induced aggregation of concentrated protein solutions, contrary to the conventional belief that arginine is a universal suppressor of aggregation. Results show that the enhancement in aggregation is caused only for BSA and BLG, but not for LYZ, indicating that arginine's preferential interactions with certain residues over others could determine the effect of the additive on aggregation. We use this previously unrecognized behavior of arginine, in combination with density functional theory calculations, to identify the molecular-level interactions of arginine with various residues that determine arginine's role as an enhancer or suppressor of aggregation of proteins. The experimental and computational results suggest that the guanidinium group of arginine promotes aggregation through the hydrogen-bond-based bridging interactions with the acidic residues of a protein, whereas the binding of the guanidinium group to aromatic residues (aggregation-prone) contributes to the stability and solubilization of the proteins. The approach, we describe here, can be used to select suitable additives to stabilize a protein solution at high concentrations based on an analysis of the amino acid content of the protein.     

Development of Controlled-Release Matrix Tablet of Risperidone: Influence of Methocel®- and Ethocel®-Based Novel Polymeric Blend on <Emphasis Type="Italic">In Vitro</Emphasis> Drug Release and Bioavailability

Controlled-release (CR) matrix tablet of 4 mg risperidone was developed using flow bound dry granulation–slugging method to improve its safety profile and compliance. Model formulations F1, F2, and F3, consisting of distinct blends of Methocel® K100 LV-CR and Ethocel® standard 7FP premium, were slugged. Each batch of granules (250–1,000 μm), obtained by crushing the slugs, was divided into three portions after lubrication and then compressed to 9-, 12-, and 15-kg hard tablets. In vitro drug release studies were carried out in 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) using a paddle dissolution apparatus run at 50 rpm. The CR test tablet, containing 30% Methocel® and 60% Ethocel® (F3) with 12-kg hardness, exhibited pH-independent zero-order release kinetics for 24 h. The drug release rate was inversely proportional to the content of Ethocel®, while the gel layer formed of Methocel® helped in maintaining the integrity of the matrix. Changes in the hardness of tablet did not affect the release kinetics. The tablets were reproducible and stable for 6 months at 40 ± 2°C/75 ± 5% relative humidity. Risperidone and its active metabolite, 9-hydroxyrisperidone, present in the pooled rabbit’s serum, were analyzed with HPLC-UV at λ_max 280 nm. The CR test tablet exhibited bioequivalence to reference conventional tablet in addition to the significantly (p < 0.05) optimized peak concentration, C_max, and extended peak time, T_max, of the active moiety. There was a good association between drug absorption in vivo and drug release in vitro (R² = 0.7293). The successfully developed CR test tablet may be used for better therapeutic outcomes of risperidone.KEY WORDS: controlled release, dry granulation slugging method, risperidone     

Synthesis of bis-armed amino acid derivatives via the alkylation of ethyl isocyanoacetate and the Suzuki–Miyaura cross-coupling reaction

Summary. Two synthetic routes to bis-armed-α-amino acid derivatives are described. The first route involves alkylation of dibromo derivatives with ethyl isocyanoacetate under phase-transfer catalysis (PTC) conditions. The second route uses a palladium-mediated Suzuki–Miyaura cross-coupling reaction between a DL-4-boronophenylalanine derivative and aromatic diiodo (or dibromo) compounds.     

Aerobic Growth of Escherichia coli Is Reduced,and ATP Synthesis Is Selectively Inhibited when Five C-terminal Residues Are Deleted from the ? Subunit of ATP Synthase

F-type ATP synthases are rotary nanomotor enzymes involved in cellular energy metabolism in eukaryotes and eubacteria. The ATP synthase from Gram-positive and -negative model bacteria can be autoinhibited by the C-terminal domain of its ϵ subunit (ϵCTD), but the importance of ϵ inhibition in vivo is unclear. Functional rotation is thought to be blocked by insertion of the latter half of the ϵCTD into the central cavity of the catalytic complex (F₁). In the inhibited state of the Escherichia coli enzyme, the final segment of ϵCTD is deeply buried but has few specific interactions with other subunits. This region of the ϵCTD is variable or absent in other bacteria that exhibit strong ϵ-inhibition in vitro. Here, genetically deleting the last five residues of the ϵCTD (ϵΔ5) caused a greater defect in respiratory growth than did the complete absence of the ϵCTD. Isolated membranes with ϵΔ5 generated proton-motive force by respiration as effectively as with wild-type ϵ but showed a nearly 3-fold decrease in ATP synthesis rate. In contrast, the ϵΔ5 truncation did not change the intrinsic rate of ATP hydrolysis with membranes. Further, the ϵΔ5 subunit retained high affinity for isolated F₁ but reduced the maximal inhibition of F₁-ATPase by ϵ from >90% to ∼20%. The results suggest that the ϵCTD has distinct regulatory interactions with F₁ when rotary catalysis operates in opposite directions for the hydrolysis or synthesis of ATP.