Preformulation Studies of a Prodrug of Δ9-Tetrahydrocannabinol

Preformulation studies were performed on a hemiglutarate ester prodrug of Δ⁹-tetrahydrocannabinol (THC-HG), to facilitate the development of stable formulations by hot-melt methods. The various studies performed included solid-state thermal characterization, pKa, logP, aqueous and pH dependent solubility, pH stability and effect of moisture, temperature and oxygen on solid-state stability. A hot-melt method was utilized to fabricate THC-HG incorporated poly (ethylene oxide) (PEO) matrices and the bioadhesive properties, release profiles and post-processing stability of these matrices were assessed as a function of the polymer molecular weight. The prodrug exhibited a T _g close to 0°C, indicating its amorphous nature. Thermogravimetric analysis revealed a rapid weight loss after 170°C. The prodrug exhibited a seven-fold higher aqueous solubility as compared to the parent drug (THC). Also, the solubility of the compound increased with increasing pH, being maximum at pH 8. The prodrug exhibited a v-shaped pH-rate profile, with the degradation rate minimum between pH 3 and 4. The moisture uptake and drug degradation increased with an increase in relative humidity. Solid-state stability indicated that the prodrug was stable at −18°C but demonstrated higher degradation at 4°C, 25°C and 40°C (51.6%, 74.5% and 90.1%, respectively) at the end of 3-months. THC-HG was found to be sensitive to the presence of oxygen. The release of the active from the polymeric matrices decreased, while bioadhesion increased, with an increase in molecular weight of PEO.     

Thoughts of a travelling ecologist 9. What money cannot buy － monetarising ecosystem services

<正>A few years before the millennium,due to a desire to make the occasion significant,there was a flurry of activities.Various summaries and initiatives were born,mostly of transient importance,and more than one of these aresimply marks of hubris.Ecologists were not exempt from this spirit of the times-but they were successful in making an impact.A group of American ecologists initiated the Millennium Ecosystem Assessment(MEA,2005),a global exercise,to     

Development of a ploidy series from a single interspecific Trifolium repens L.Ā . nigrescens Viv. F1 hybrid

 The objective of the current research was to generate a ploidy series of backcross progenies from a single triploid (2n=3x=24) Trifolium repens×T. nigrescens F₁ hybrid (3x H-6909-5). The 3x H-6909-5 plant was highly sterile and produced no seeds from approximately 3000 reciprocal backcrosses to both parental species. Chromosome doubling by an in vitro colchicine method resulted in a marked increase in fertility. Pollen stainability was increased from 9.9% in 3x H-6909-5 to an average of 89.2% (range 87.7–90.9%) in the three chromosome-doubled 6x H-6909-5 plants. Subsequent backcrosses of 6x H-6909-5 and interbreeding of backcross derivatives resulted in an array of fertile hybrids at 4x, 5x and 7x levels and some aneuploids. The occurrence of 7x BC₁F₁ progeny from the T. repens×6x H-6909-5 (4x×6x) cross is the first unequivocal evidence of functional female 2n gametes in white clover. Meiotic pairing in F₁ and BC₁F₁ progeny indicated the presence of allosyndetic pairing, suggesting that genetic exchange between the two species is possible. Received: 17 October 1996 / Accepted: 8 November 1996     

9-Cis-retinoyl-β-glucuronide is a major metabolite of 9-Cis-retinoic acid

The in vivo metabolism of 9-cis-retinoic acid (9-c-RA), an endogenous ligand of retinoid X receptors (RXRs), which can also bind to retinoic acid receptors (RARs), was examined in pregnant mice and rats following a single oral dose of 100 mg 9-cis- retinaldehyde (9-c-RAL) / kg body weight. 9-Cis-retinoyl-β-glucuronide (9-c-RAG), a metabolite not found in vivo before, was a major metabolite of 9-c-RA in mouse plasma and was also present in all mouse tissues examined as well as in rat plasma. In both species putative oxidation products of retinoic acids and high levels of retinyl esters were found. Concentrations of retinoic acid isomers and retinoyl-β-D-glucuronides in the mouse plasma greatly exceeded those of the rat plasma. The finding of high levels of 9-c-RAG underlines the importance of glucuronidation in the metabolism of retinoids.     

M?ssbauer studies of the formation and reactivity of a quasi-stable peroxo intermediate of stearoyl-acyl carrier protein Delta 9-desaturase.

Stearoyl-ACP Delta(9)-desaturase (Delta 9D) is a diiron enzyme that catalyzes 18:0-ACP desaturation. Each subunit of homodimeric resting Delta 9D contains a diferric cluster, while chemical reduction by 4e(-) produces a diferrous cluster in each subunit. Reaction of 4e(-)-reduced Delta 9D with 18:0-ACP and O(2) yields a blue chromophore (lambda(max) approximately 700 nm) that exhibits a vibrational spectrum indicative of a micro-1,2-peroxo complex; this species has been designated peroxo Delta9D. In contrast to other enzymic peroxodiiron intermediates, peroxo Delta 9D is long-lived (t(1/2) approximately 30 min at 25 degrees C) and decays via an oxidase reaction without formation of either H(2)O(2) or product (18:1-ACP). In this work, optical, transient kinetic, and M?ssbauer techniques have been used to further investigate the origin and nature of this unusual peroxodiiron complex. Rapid mixing of 4e(-) Delta 9D with O(2)-equilibrated 18:0-ACP produced peroxo Delta 9D as revealed by a temperature-dependent, pseudo-first-order absorption increase at 700 nm (k = 46 s(-)(1) at 6 degrees C). The M?ssbauer spectrum of peroxo Delta 9D, accounting for 96% of the total iron, consists of two quadrupole doublets present in equal proportions: delta(1) = 0.68(1) mm/s, and Delta E(Q)(1) = 1.90(2) mm/s; delta(2) = 0.64(1) mm/s, and Delta E(Q)(2) = 1.06(2) mm/s. Decay of the 700 nm optical band (k = 0.004 min(-)(1) at 6 degrees C) correlates with the complete conversion of peroxo Delta 9D into a complex called peroxo-cycled Delta 9D, which exhibits two new doublets present in equal proportions: delta(1) = 0.57(2) mm/s, and Delta E(Q)(1) = 1. 91(3) mm/s; delta(2) = 0.52(2) mm/s, and Delta E(Q)(2) = 1.41(3) mm/s. Thus, peroxo Delta 9D contains two asymmetric diferric clusters and reacts to yield peroxo-cycled Delta 9D, also containing two asymmetric diferric clusters that most probably represent a substrate complex state. The clusters of both peroxo Delta 9D and peroxo-cycled Delta 9D have a diamagnetic ground state. Because peroxo Delta 9D and peroxo-cycled Delta 9D are observed only in the presence of 18:0-ACP, substrate binding appears to have introduced asymmetry into the Delta 9D diiron clusters. In situ photolysis of peroxo Delta 9D at 4.2 K in the M?ssbauer cryostat caused the release of O(2) and the reappearance of a diferrous Delta 9D.18:0-ACP complex with slightly changed parameters, suggesting a constrained cluster configuration was produced by the photolysis event. Annealing the photolyzed sample for 30 min at 77 K quantitatively restored the M?ssbauer spectrum of peroxo Delta 9D, showing that the released O(2) was effectively sequestered within the active site.     

A Neglected Character of Cornus L. s. 1. with Special Reference to a New Subgenus—Sinocornus Q. Y. Xiang

Cornus L. s. 1. is a large polytypic genus. The classificantion of which has been so different that some authors recognize several separate genera, while others treat them as either subgenera or sections. New evidence from many disciplines such as palynology, cytology, wood anatomy and embryology supports the view that the genus should remain in the broad sense. I basically agree with the treatment by Ferguson (1966_b) before my finishing a comprehensive study on Cornus L. s. 1. except for supporting the separation of subgenus Afrocrania as an independent genus. A new subgenus Sinocornus Q. Y. Xiang, containing one species, C. chinensis Wangerin, is established here on account of its inflorescence axillary and different from the other members of the genus which all have terminal inflorescences only. The inflorescence developed from a terminal bud implicates the sympodial nature of axis of stem and the one from an axillary bud the monopodial one. It is reasonable to regard the character as of subgeneric value. Also a new combination, Cornus subgen. Syncarpea (Nakai) Q. Y. Xiang, is proposed here as a substitute for Cornus subgen. Benthamia (C. B. Clarke) Schneider used for a long time. Because the valid publication of the former name subgen. Syncarpea Nakai is earlier than the latter one. The types of inflorescences of 8 subgenera represented by type or selected species are illustrated.     

斑马鱼sat1.a突变体的鉴定

目的在我们的前期研究工作中,通过Tol2转座子介导的插入突变,筛选到了一批组织特异性表达绿色荧光蛋白GFP的斑马鱼品系。其中一个品系Tol2:20141221t的GFP在神经系统中表达,但还没有鉴定到Tol2转座子插入到基因组什么位置,造成了哪个基因的突变。本文的主要研究目标就是对这一由Tol2转座子插入诱导的斑马鱼突变品系进行鉴定。方法使用交错式热不对称PCR(thermal asymmetric interlaced PCR,TAIL-PCR)鉴定Tol2转座子插入的基因组位置;利用原位杂交检测被突变的基因的时空表达是否与该品系GFP表达具有一致性;筛选鉴定纯合体突变体,并进一步分析该基因突变造成的发育缺陷。结果在该品系中,Tol2转座子插入到了亚精胺/精胺N1-乙酰基转移酶1a(spermidine/spermine N1-acetyltransferase 1a,sat1.a)的第八个内含子区域,致使sat1.a基因转录提前终止。我们筛选到了sat1.a纯合突变体,但是没有检测到明显的发育缺陷。结论筛选鉴定的Tol2转座子介导的斑马鱼sat1.a突变体没有明显的发育缺陷,但可以作为研究神经系统发育的有力工具。     

Babjevia gen. nov. — a new genus of the Lipomycetaceae

The species described asLipomyces anomalus Babjeva & Gorin shows significant genetic and phenotypic divergence from the type speciesLipomyces starkeyi Lodder & Kreger-van Rij in terms of rRNA base sequence substitution and ascosporal and septal ultrastructure. The species is consequently reclassified in the new, unispecific genusBabjevia, asBabjevia anomala.     

16. Dispersal of freshwater algae — a review

A survey is given on the various methods for dispersal of freshwater algae. Dispersal factors are either water or air, or organisms — from beetles, dragonflies and mammals to birds, the latter being the most important group. The question of dispersal distances is discussed, in relation to dispersal mechanisms and to the resistance of the algae to transport conditions. Man's recent importance in algal dispersal is emphasized.     

Response to: Turner,R.E., J.E. Bodker,and C. Schulz. 2017. The belowground intersection of nutrients and buoyancy in a freshwater marsh. Wetlands Ecology & Management: 1–9

Wetlands Ecology and Management -     

Cell-wall Polysaccharides of Immature Barley Plants. I. Isolation and Characterization of a β-d-Glucan

A β-d-glucan was isolated on fractionation of a 4% potassium hydroxide extract (hemi-celluloses) of immature barley plants (Hordeum distichum L.). Most of the glucose residues in the extract were found to be derived from the glucan. Methylation analysis and enzyme degradation studies showed that the glucan had (l-→3)-and (1-→4)-linked d-glucopyranosyl residues in an approximate molar ratio of 1.0:2.3. The molecular weight of the glucan was estimated to be 1.8 x 10⁵ by gel filtration on Sepharose CL-6B.     

Adenosine Receptor Agonists. X-Ray Crystal Structure of Neca 1-(6-Amino-9H-Purin-9-Yl)-1-Deoxy-N-Ethyl-β-D-Ribofuranuronamide

Abstract

The single crystal x-ray structure of NECA (1-(6-amino-9H-pu-rin-9-yl)-1-deoxy-N-ethyl-β-D-ribofuranuronamide), a 5′-modified adenosine analogue, is reported. Crystallized from methanol as the monohydrate, NECA exists in a syn conformation (sugar syn to purine) in the solid state, consistent with both solution measurements and theoretical calculations. The biological profile of NECA may result from this conformational preference.     

Thoughts of a travelling ecologist 17.One biosecurity

The still-untamed SARS-CoV-2 pandemic underlined,again,two important facts that have been known for a long while but conveniently forgotten by humankind.One is that we are profoundly linked to other organisms and nature,and the other is that human-driven distribution chains are global and fast.