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Qualitative evidence of service user experiences and perspectives on long-acting injectable buprenorphine for opioid treatment - a scoping review.

BACKGROUND: There is substantial literature on opioid treatment program (OTP) formulations and how they relate to the pharmacotherapy service user experience. As a newer formulation, less is known about service user experiences of long-acting injectable buprenorphine (LAIB). The aim of this scoping review is to map the qualitative evidence and gaps in the literature on service user experiences and perspectives of LAIB. METHODS: Our search strategy included Medline, Embase, PsycINFO, CINAHL, Scopus and Web Science, and citation chaining, from January 2016 to June 2025. Studies were included if reporting qualitative descriptions of LAIB service user experiences of treatment for opioid dependence, inclusive of qualitative, mixed methods (description of qualitative data only), case reports and English language. Articles were screened by two reviewers. A living experience first author led the analysis using inductive coding and thematic analysis, to produce a descriptive summary of synthesised findings alongside key study characteristics and quality appraisal, adhering to the Systematic reviews and Meta-Analysis for Scoping Reviews (PRISMA-ScR) checklist. RESULTS: After screening 838 titles/abstracts and reviewing 150 full texts, 40 studies met the eligibility criteria. All were conducted in high income countries, principally the US (n=12); Australia (n=10); and England and Wales (n=9). We identified five themes: Navigating LAIB treatment; Embodied and relational effects of LAIB; Impact and role of the service provider; Narratives of harm reduction and recovery; Stigma and criminalisation. LAIB was commonly experienced as increasing convenience, stability and freedom from daily supervised dosing, enabling improved work, travel, privacy and social participation. Reduced clinic/dosing contact often lessened enacted stigma and treatment burden. However, experiences were heterogenous. Some participants described injection-site discomfort, uncertainty about dose adequacy, reduced flexibility once injected, and ambivalence about LAIB effects. There was inconsistency in LAIB service user reports on service connection, isolation and psychosocial support. Treatment experiences were strongly shaped by provider practices. CONCLUSIONS: Findings underscore the need for integrated, flexible, harm-reduction oriented and person-centred LAIB treatment models that prioritise choice, autonomy and therapeutic relationships to maximise benefit for service users. However, evidence of LAIB service user experiences is concentrated in high-income countries, and the absence of perspectives from low- and middle-income country settings represents a substantial gap in the evidence base.

LAIB

Alkylation of RNA by vinyl bromide metabolites in vitro and in vivo.

[1,2-14C]Vinyl bromide was incubated with rat liver microsomes, NADPH, and polyadenylic acid, polycytidylic acid, or RNA, respectively. Part of the adenosine moieties in RNA or in polyadenylic acid were alkylated and labelled 1,N6-ethenoadenosine structures were formed. Part of the cytidine moieties were converted into 3,N4-ethenocytidine. In addition, a further unidentified cytidine alkylation product was observed which was not seen in experiments using [1,2-14C]vinyl chloride. When rats were exposed to [1,2-14C]vinyl bromide, radioactive ethenoadenosine and ethenocytidine were present in hydrolysates of liver RNA. A further alkylation product was observed in the RNA hydrolysates which did not occur in experiments using [14C]vinyl chloride. The data show that vinyl bromide metabolites alkylate nucleic acids; although in general in this respect vinyl bromide and vinyl chloride behave similarly, some differences are observed in the alkylation behaviour of both compounds.

Alkylation

Formation of 3,N4-ethenocytidine moieties in RNA by vinyl chloride metabolities in vitro and in vivo.

Rats were exposed to [1,2-14C] vinyl chloride. Liver RNA was isolated, hydrolyzed, and the nucleosides separated on Aminex-A-6. Besides the physiological bases and 1,N6-ethenoadenosine, radioactivity was also incorporated into 3,N4-ethenocytidine. Radioactive 3,N4-ethenocytidine moieties were also formed on incubation of polycytidylic acid with rat liver microsomes, NADPH and [14C] vinyl chloride. These alkylation mechanisms are consistent with the mutagenic and cancerogenic properties of vinyl chloride.

Animals

Vinyl chloride and trichloroethylene: comparison of alkylating effects of metabolites and induction of preneoplastic enzyme deficiencies in rat liver.

[1,2-14C] Vinyl chloride and [1,2-14C] trichloroethylene were incubated with rat liver microsomes, NADPH and RNA (from yeast). Whereas trichloroethylene metabolites were irreversibly bound to proteins in microsomal incubations to a higher extent than vinyl chloride metabolites, irreversible binding to RNA was lower for trichloroethylene metabolites. Hydrolysis of the RNA which was reisolated from microsomal incubations with 14C-vinyl chloride or 14C-trichloroethylene and separation of the nucleosides showed different alkylation products arising from vinyl chloride and from trichloroethylene, characteristic for vinyl chloride being formation of 1,N6-ethenoadenosine and 3,N4-enthenocytidine. The different reactivities of metabolites of vinyl chloride and of trichloroethylene prompted a comparison of the oncogenic effects of both compounds against the rat liver cell. Newborn rats were exposed for 10 weeks to 2000 ppm vinyl chloride or trichloroethylene (8 h/day; 5 days/week). After this period livers of the animals were stained for nucleoside-5-triphosphatase. Whereas the vinyl chloride exposed rats showed focal hepatocellular deficiencies in this enzyme, which are supposed to represent an early sign of malignancy, no such changes were induced by trichloroethylene exposure. The data therefore suggest differences between the hepatocarcinogenic activity of vinyl chloride and possible effects of trichloroethylene on the liver.

Adenosine

Mutagenicity of 2-methylpropene (isobutene) and its epoxide in a modified Salmonella assay for volatile compounds.

The mutagenic properties of 2-methylpropene (MP) and 2-methyl-1,2- epoxypropane (MEP) were investigated in the Salmonella assay. A simple exposure system, consisting of gastight tissue culture flasks, was used. This method has the advantage that the volatile test chemical is present during the entire incubation period and that several concentrations of the investigated compound can be tested on a single day. MP is not mutagenic in strains TA100, TA102 and TA1535, and in the latter strain not even in the presence of metabolizing S9 mix. MEP is mutagenic in all the strains tested, as demonstrated by a clear dose-response relationship. Strain TA1535 seems to be most sensitive to MEP compared with the other bacterial strains studied. For this strain, the mutagenic activity of MEP decreased significantly in the presence of S9 mix, compatible with the epoxide being inactivated by epoxide hydrolase and by glutathione S-transferase, as reported previously. From the present study it can be concluded that the parent compound MP is not mutagenic, but that its primary metabolite MEP is a mutagenic substance. However, very high concentrations are necessary to induce a mutagenic effect and the epoxide is efficiently detoxified by different liver enzymes.

Alkenes

Alkylation of RNA by vinyl chloride metabolites in vitro and in vivo: formation of 1-N(6)-etheno-adenosine.

Rat liver microsomes were incubated with NADPH, 1,2-[(14)C] vinyl chloride and poly-adenosine. The latter was reisolated from the incubations and hydrolyzed. The radioactivity, originating from [(14)C] vinyl chloride, which was irreversibly attached to the poly-adenosine was confined to 1-N(6)-etheno-adenosine (3beta-ribofuranosyl-imidazo [2,1,i] purine). When rats were exposed to 1,2-[(14)C] vinyl chloride, part of the radioactivity was incorporated into RNA of liver. This radioactive labelling exhibited a first maximum, 14 h, and a second maximum, 72 h after ending the exposure. Analysis of hydrolysate of liver RNA showed that all natural nucleosides of RNA were labelled. Besides, small amounts of radioactivity could be detected which were confined to 1-N(6)-etheno-adenosine. The experiments support the theory that vinyl chloride metabolites react with adenosine moieties of nucleic acid under formation of 1-N(6)-etheno-adenosine. Furthermore, the results show that measurement of incorporation of radioactivity into nucleic acids after exposure of animals to radioactive vinyl chloride is not applicable as a means of determining the alkylating potency of vinyl chloride metabolites towards nucleic acids in vivo.

Adenine Nucleotides

Pharmacokinetics of vinyl chloride in the rat.

When rats are exposed to [14C]vinyl chloride in a closed system, the vinyl chloride present in the atmosphere equilibrates with the animals' organism within 15 min. The course of equilibration could be determined using rats which had been given 6-nitro-1,2,3-benzothiadiazole. This compound completely blocks metabolism of vinyl chloride. The enzymes responsible for metabolism of vinyl chloride are saturated at an atmospheric concentration of vinyl chloride of 250 ppm. Pharmacokinetic analysis shows that no significant cumulation of vinyl chloride or its major metabolites is to be expected on repeated administration of vinyl chlorides. This may be consistent with the theory that a reactive, shortly living, metabolite which occurs in low concentration only, may be responsible for the toxic effects of vinyl chloride.

Animals

Horizontal fracture of the anterior arch of the atlas.

Horizontal fracture of the anterior arch of the atlas can be easily overlooked on lateral radiographs. The fracture is not associated with neurological deficit but may be the cause of severe pain. A review of the literature reveals only 3 previously reported cases. Seven new cases, including 2 without other cervical spine fractures, indicate a much higher incidence than was previously thought. Hypotheses about the mechanism of injury are discussed.

Cervical Atlas