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1.
Addiction ; 115(12): 2200-2207, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32107849

RESUMO

BACKGROUND: In the recent case of R v. Taj, the Court of Appeal of England and Wales upheld the conviction of a defendant who, in a psychotic delusional state, mistook his non-threatening victim to be a terrorist, violently attacking him. The law typically allows honest mistakes (even if unreasonable) as a basis for self-defence (in this case the defence of others). However, because Taj's delusions were found by the court to have been caused by voluntary alcohol consumption, special legal (prior-fault) intoxication rules were applied to block his defence; Taj was convicted and sentenced to 19 years imprisonment for attempted murder. ARGUMENT: We focus here on the simple question-what does it mean to be intoxicated? On the facts, Taj did not have drugs active in his system at the time of the attack, but the court nonetheless insisted that Taj's delusional mistake was 'attributable to intoxication'; namely, to drink- and drug-taking in the previous days and weeks. This extended conception of intoxication was questionably distinguished from psychosis induced by withdrawal. Furthermore, the court was unreceptive to evidence of a long-standing, underlying mental health disorder. We argue that the court's expanded view of intoxication is problematic, in that intoxication-induced psychosis cannot be sharply distinguished from other causes such as mental disorders; and even if it could be distinguished, it should not give rise to blame and punishment in the same way as does conduct induced by chemically active intoxicants ('drug-on-board'). CONCLUSION: The courts' expansion of the definition of intoxication is both legally and forensically problematic, introducing legal vagaries where the clinical science is already vague; and with intoxication frequently interlocking with historic intoxication and secondary or comorbid mental health conditions, the decision risks inappropriately and/or over-criminalizing defendants.


Assuntos
Intoxicação Alcoólica/psicologia , Direito Penal/legislação & jurisprudência , Transtornos Psicóticos/psicologia , Agressão , Comportamento Perigoso , Inglaterra , Humanos , Masculino , Proibitinas
3.
Pharm Res ; 12(1): 60-8, 1995 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7724489

RESUMO

Mixing pharmaceutical preparations of soluble neutral regular insulin solution (NRI) and neutral protamine Hagedorn (NPH) crystalline insulin suspension leads to a reduction in the measurable amount of soluble insulin in the formulation supernatant. However in spite of the loss in soluble insulin, the time-actions of these components have been shown, in clinical trials, to be unaffected. The interaction between these different physical forms of insulin has been studied using reversed-phase HPLC, isothermal titrating calorimetry, and Doppler electrophoretic light scattering analysis. Sorbent surface and solution perturbation studies revealed that the NRI adsorbs to the surface of the NPH crystal with an equilibrium constant ranging from 10(4) M-1 to 10(7) M-1, depending on the protamine concentration, pH, ionic strength, and temperature. This adsorption behavior suggests that the binding is mediated by electrostatic interactions arising between the positively-charged NPH crystal and the negatively-charged NRI hexamer. Doppler electrophoretic light scattering results, used to probe the pH-dependent surface charge of NPH and soluble insulin hexamer, support the conclusion that electrostatic interactions mediate the adsorption process. Adsorption studies under physiological conditions indicate that the elevated temperature and ionic strength, in a subcutaneous depot, are sufficient to lead to the dissociation of the NRI/NPH complex that exists in these NPH mixture formulations.


Assuntos
Insulina/química , Protaminas/química , Adsorção , Soluções Tampão , Fenômenos Químicos , Química Farmacêutica , Físico-Química , Cristalização , Eletroquímica , Concentração de Íons de Hidrogênio , Cinética , Concentração Osmolar , Conformação Proteica , Soluções , Temperatura
4.
Biotechnol Bioeng ; 41(5): 572-80, 1993 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-18609589

RESUMO

Pure cultures of Pseudomonas putida (ATCC 17484) were grown in continuous culture on phenol at dilution rates of 0.074-0.085 h(-1) and subjected to step increases in phenol feed concentration. Three distinct patterns of dynamic response were obtained depending on the size of the step change used: low level, moderate level, or high level. During low level responses no accumulations of phenol or non-phenol, non-glucose-dissolved organic carbon, DOC(NGP), were observed. Moderate level responses were characterized by the transient accumulation of DOC(NGP) with a significant delay prior to phenol leakage. High level responses demonstrated a rapid onset of phenol leakage and no apparent accumulations of DOC(NGP). The addition of phenol to a continuous culture of the same organism on glucose did not result in transient DOC(NGP) accumulations, although transient phenol levels exceeded 90 mg l(-1). These results were consistent with intermediate metabolite production during phenol step tests coupled with substrate-inhibited phenol uptake and suggested that traditional kinetic models based on the Haldane equation may be inadequate for describing the dynamics of phenol degrading systems.

5.
Proc Natl Acad Sci U S A ; 77(10): 5580-2, 1980 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-6932658

RESUMO

The self-association of guanosine, cytidine, and adenosine and base pairing between guanosine, cytidine, adenosine, and uridine in dimethyl sulfoxide have been investigated by the variation of their 15N NMR chemical shifts with concentration and temperature. Guanosine, cytidine, and adenosine all showed evidence of self-association by hydrogen bonding. In guanosine/cytidine mixtures, a hydrogen-bonded dimer is formed; however, no base pairing could be detected with adenosine/cytidine or adenosine/uridine mixtures.


Assuntos
Físico-Química , Dimetil Sulfóxido/farmacologia , Ligação de Hidrogênio , Nucleosídeos , Fenômenos Químicos , Espectroscopia de Ressonância Magnética , Solventes/farmacologia , Temperatura
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