Salt and ionic cocrystalline forms of amides: protonation of carbamazepine in aqueous media

The products of reactions of the pharmaceutical amide carbamazepine (CBZ) with strong acids under aqueous conditions were investigated by both powder and single crystal X-ray diffraction. Despite previous claims to the contrary, it was found that salt forms with CBZ protonated at the amide O atom could be isolated from reactions with both HCl and HBr. These forms include the newly identified hydrate phase [CBZ(H)][Cl]·H O. Reactions with other mineral acids (HI and HBF ) gave ionic cocrystalline (ICC) forms (CBZ· [acridinium][I ]·2.5I and CBZ·[H O ] [BF ] ·H O) as well as the salt form CBZ·[CBZ(H)][BF ]·0.5H O. Reaction 2 4 3 2 5 2 0.25 4 0.25 2 4 2 of CBZ with a series of sulfonic acids also gave salt forms, namely, [CBZ(H)][O SC H ], [CBZ(H)][O SC H (OH)]· 3 6 5 3 6 4 0.5H O, [CBZ(H)] [O SCH CH SO ], and [CBZ(H)][O SC H (OH) (COOH)]·H O. CBZ and protonated CBZ(H) 2 2 3 2 2 3 3 6 3 2 moieties can be differentiated in the solid state both by changes to molecular geometry and by differing packing preferences

The spaces of the Wednesday Play (BBC TV 1964–1970): production, technology and style

The BBC television drama anthology The Wednesday Play, broadcast from 1964-70 on the BBC1 channel, was high-profile and often controversial in its time and has since been central to accounts of British television’s ‘golden age’. This article demonstrates that production technologies and methods were more diverse at that time than is now acknowledged, and that The Wednesday Play dramas drew both approving but also very critical responses from contemporary viewers and professional reviewers. This article analyses the ways that the physical spaces of production for different dramas in the series, and the different technologies of shooting and recording that were adopted in these production spaces, are associated with but do not determine aesthetic style. The adoption of single-camera location filming rather than the established production method of multi-camera studio videotaping in some of the dramas in the series has been important to The Wednesday Play’s significance, but each production method was used in different ways. The dramas drew their dramatic forms and aesthetic emphases from both theatre and cinema, as well as connecting with debates about the nature of drama for television. Institutional and regulatory frameworks such as control over staff working away from base, budgetary considerations and union agreements also impacted on decisions about how programmes were made. The article makes use of records from the BBC Written Archives Centre, as well as published scholarship. By placing The Wednesday Play in a range of overlapping historical contexts, its identity can be understood as transitional, differentiated and contested.

The impact of contractor selection method on transaction costs: a review

The basic premise of transaction-cost theory is that the decision to outsource, rather than to undertake work in-house, is determined by the relative costs incurred in each of these forms of economic organization. In construction the "make or buy" decision invariably leads to a contract. Reducing the costs of entering into a contractual relationship (transaction costs) raises the value of production and is therefore desirable. Commonly applied methods of contractor selection may not minimise the costs of contracting. Research evidence suggests that although competitive tendering typically results in the lowest bidder winning the contract this may not represent the lowest project cost after completion. Multi-parameter and quantitative models for contractor selection have been developed to identify the best (or least risky) among bidders. A major area in which research is still needed is in investigating the impact of different methods of contractor selection on the costs of entering into a contract and the decision to outsource.

Comparing rice production systems: A challenge for agronomic research and for the dissemination of knowledge-intensive farming practices

This article is a commentary on several research studies conducted on the prospects for aerobic rice production systems that aim at reducing the demand for irrigation water which in certain major rice producing areas of the world is becoming increasingly scarce. The research studies considered, as reported in published articles mainly under the aegis of the International Rice Research Institute (IRRI), have a narrow scope in that they test only 3 or 4 rice varieties under different soil moisture treatments obtained with controlled irrigation, but with other agronomic factors of production held as constant. Consequently, these studies do not permit an assessment of the interactions among agronomic factors that will be of critical significance to the performance of any production system. Varying the production factor of "water" will seriously affect also the levels of the other factors required to optimise the performance of a production system. The major weakness in the studies analysed in this article originates from not taking account of the interactions between experimental and non-experimental factors involved in the comparisons between different production systems. This applies to the experimental field design used for the research studies as well as to the subsequent statistical analyses of the results. The existence of such interactions is a serious complicating element that makes meaningful comparisons between different crop production systems difficult. Consequently, the data and conclusions drawn from such research readily become biased towards proposing standardised solutions for possible introduction to farmers through a linear technology transfer process. Yet, the variability and diversity encountered in the real-world farming environment demand more flexible solutions and approaches in the dissemination of knowledge-intensive production practices through "experiential learning" types of processes, such as those employed by farmer field schools. This article illustrates, based on expertise of the 'system of rice intensification' (SRI), that several cost-effective and environment-friendly agronomic solutions to reduce the demand for irrigation water, other than the asserted need for the introduction of new cultivars, are feasible. Further, these agronomic Solutions can offer immediate benefits of reduced water requirements and increased net returns that Would be readily accessible to a wide range of rice producers, particularly the resource poor smallholders. (C) 2009 Elsevier B.V. All rights reserved.

Degradation products of clavulanic acid promote clavulanic acid production in cultures of Streptomyces clavuligerus

The role of clavulanic acid, an unstable antibiotic produced by Streptomyces clavuligerus, in biomass accumulation and production of clavulanic acid in batch cultures of the organism was examined. The organism was grown in a medium containing either 20 g/l lysine, 1 g/l lysine or 1 g/l lysine supplemented with degraded clavulanic acid as nitrogen sources. Biomass accumulation was highest in cultures grown with supplemented degraded clavulanic acid and reached a maximum of 2.2 g/l, compared with 1.5 g/l when lysine only was used. The yield coefficient for clavulanic acid production was again highest in cultures grown with supplemented degraded clavulanic acid, with a Y-p/x, value of 2 mg/g compared with Y-p/x value of 1.5 mg/g in 20 g/l lysine. No clavulanic acid was produced in cultures containing non-supplemented 1 g/l lysine. Non-degraded clavulanic, acid was added at 60 h to non-producing cultures of the organism containing 1 g/l lysine only. Clavulanic acid concentration immediately decreased on addition from 0.04 g/l over a period of 20 h, then remained constant at 0.02 g/l for a further 30 h until the end of the cultivation. This suggests that the rate of degradation was equivalent to the rate of production of clavulanic acid following a period of initial additive degradation. These results indicate that clavulanic acid is both produced and degraded in cultures of S. clavuligerus and that the products of degradation are used by the organism, resulting in further production of the antibiotic. (C) 2003 Elsevier Inc. All rights reserved.

Adverse gastrointestinal effects of arginine and related amino acids

Oral supplements of arginine and citrulline increase local nitric oxide (NO production in the small intestine and this may be harmful under certain circumstances. Gastrointestinal toxicity was therefore reviewed with respect to the intestinal physiology of arginine, citrulline, ornithine, and cystine (which shares the same transporter) and the many clinical trials of supplements of the dibasic amino acids or N-acetylcysteine (NAC. The human intestinal dibasic amino acid transport system has high affinity and low capacity. L-Arginine (but not lysine, ornithine, or D-arginine) induces water and electrolyte secretion that is mediated by NO, which acts as an absorbagogue at low levels and as a secretagogue at high levels. The action of many laxatives is NO mediated and there are reports of diarrhea following oral administration of arginine or ornithine ihine. The clinical data cover a wide span of arginine intakes f rom 3 g/d to > 100 g/d, but the standard of reporting adverse effects (e.g. nausea, vomiting, and diarrhea) was variable. Single doses of 3-6 g rarely provoked side effects and healthy athletes appeared to be more susceptible than diabetic patients to gastrointestinal symptoms at individual doses >9 g. This may relate to an effect of disease on gastrointestinal motility and pharmacokinetics. Most side effects of arginine and NAC occurred at single doses of >9 g in adults >140 mg/kg) often when part of a daily regime of similar to>30 g/d (>174 mmol/d). In the case of arginine, this compares with the laxative threshold of the nonabsorbed disaccharide alcohol, lactitol (74 g or 194 mmol). Adverse effects seemed dependent on the dosage regime and disappeared if divided doses were ingested (unlike lactitol). Large single doses of poorly absorbed amino acids seem to provoke diarrhea. More research is needed to refine dosage strategies that reduce this phenomenon. It is suggested that dipeptide forms of arginine may meet this criterion.

Two-dimensional similarity between forms I and II of cytenamide, a carbamazepine analogue

Cytenamide form I (R (3) over bar) undergoes a solid-state transformation upon heating to form II (P (1) over bar), with the structures exhibiting the same two-dimensional similarity that exists between the R (3) over bar and P (1) over bar forms of carbamazepine.

Farming and food production and development in the Shropshire Hills Environmentally Sensitive Area, 1997-2008

European agricultural and environmental policy has evolved considerably over the last 15 years. In this paper the changes in farm businesses in an Environmentally Sensitive Area in England are evaluated based on two surveys with the same farmers at the start and end of this period. The rate of participation in the environmental scheme had increased significantly at a time when Government led goals in this area had developed and become more output focussed. A combination of policy, market and animal health status changes had encouraged a number to leave cattle production, and though remaining with stock and grass they had decided against any extensive development in the direction of pluriactivity – with or without Government encouragement. This left the future of this group in some uncertainty given that two significant forms of financial support, the environmental scheme and the Hill Farm Allowance, were due to close.

Metabolism of tea flavonoids in the gastrointestinal tract

There is considerable interest in the bioavailability of flavan-3-ols such as tea catechins and their bioactivity in vivo. Although flavanols such as catechin and epicatechin have long been characterized as powerful antioxidants in vitro, evidence suggests that these compounds undergo significant metabolism and conjugation during absorption in the small intestine and in the colon. In the small intestine these modifications lead primarily to the formation of glucuronide conjugates that are more polar than the parent flavanol and are marked for renal excretion. Other phase II processes lead to the production of O-methylated forms that have reduced antioxidant potential via the methylation of the B-ring catechol. Significant modification of flavanols also occurs in the colon where the resident microflora degrade them to smaller phenolic acids, some of which may be absorbed. Cell, animal and human studies have confirmed such metabolism by the detection of flavanol metabolites in the circulation and tissues. This review will highlight the major sites of flavanol metabolism in the gastrointestinal tract and the processes that give rise to potential bioactive forms of flavan-3-ols in vivo.

Shifts in metabolic scaling, production, and efficiency across major evolutionary transitions of life

The diversification of life involved enormous increases in size and complexity. The evolutionary transitions from prokaryotes to unicellular eukaryotes to metazoans were accompanied by major innovations inmetabolicdesign.Hereweshowthat thescalingsofmetabolic rate, population growth rate, and production efficiency with body size have changed across the evolutionary transitions.Metabolic rate scales with body mass superlinearly in prokaryotes, linearly in protists, and sublinearly inmetazoans, so Kleiber’s 3/4 power scaling law does not apply universally across organisms. The scaling ofmaximum population growth rate shifts from positive in prokaryotes to negative in protists and metazoans, and the efficiency of production declines across these groups.Major changes inmetabolic processes duringtheearlyevolutionof life overcameexistingconstraints, exploited new opportunities, and imposed new constraints. The 3.5 billion year history of life on earth was characterized by

The Life of Galileo and Brechtian television drama

Bertolt Brecht's dramaturgy was as influential upon the development of British drama on television between the 1950s and the 1970s as it was in the theatre. His influence was made manifest through the work of writers, directors and producers such as Tony Garnett, Ken Loach, John McGrath and Dennis Potter, whose attempts to create original Brechtian forms of television drama were reflected in the frequent reference to Brecht in contemporary debate concerning the political and aesthetic direction and value of television drama. While this discussion has been framed thus far around how Brechtian techniques and theory were applied to the newer media of television, this article examines these arguments from another perspective. Through detailed analysis of a 1964 BBC production of The Life of Galileo, I assess how the primary, canonical sources of Brecht's stage plays were realised on television during this period, locating Brecht's drama in the wider context of British television drama in general during the 1960s and 1970s. I pay particular attention to the use of the television studio as a site that could replicate or reinvent the theatrical space of the stage, and the responsiveness of the television audience towards Brechtian dramaturgy.

Meat quality and health implications of organic and conventional beef production

Recommendation to reduce fat consumption from ruminant meat does not consider the contribution of nutritionally beneficial fatty acids in lean beef. Here we report effects of production system (organic vs conventional) and finishing season on meat and fat quality of sirloin steaks from retail outlets and simulated fatty acid intakes by consumers. There was little difference in meat quality (pH, shear force and colour), but the fat profiles varied considerably between production systems and season. Meat fat from organic and summer finished cattle contained higher concentrations of conjugated linoleic acid, its precursor vaccenic acid and individual omega-3 fatty acids and had a lower ratio of omega-6 to omega-3 fatty acids compared with non-organic and winter finished cattle respectively. The fat profile from summer finished organic beef aligns better to recommended dietary guideline including those for long chain omega-3 fatty acids compared with that from winter finished, non-organic steak.