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1.
Am J Transplant ; 22(10): 2467-2469, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35612995

RESUMO

In living donor liver transplantation, hepatic artery intimal dissection is a rare but devastating complication often resulting in the inability to utilize the graft. We detail the salvage of a dissected donor right hepatic artery utilizing the recipient hepatic artery. After removal of the right lobe, the donor artery was found to have an intimal dissection extending to multiple branches. The liver transplant surgeons requested their plastic microsurgeon colleague to assist with reconstruction. Ultimately, the native recipient hepatic artery was used as a branch graft as the caliber and branching pattern was appropriate. Back table microvascular reconstruction was performed using the explanted recipient hepatic artery branches as a graft to the four donor artery branches. Every anastomosis was assessed with intraoperative doppler; all were patent with acceptable flow characteristics. The patient did well post-operatively with post-operative ultrasounds demonstrating patency of the graft. Four months post-transplantation the patient developed two polymicrobial abscesses that were drained and resolved with normalization of liver function tests. This case highlights how collaboration with a microvascular surgeon enabled the salvage of a living donor graft when faced with a complex arterial dissection.


Assuntos
Transplante de Fígado , Doadores Vivos , Anastomose Cirúrgica , Artéria Hepática/cirurgia , Humanos , Fígado/cirurgia , Transplante de Fígado/métodos , Plásticos
2.
ACS Chem Neurosci ; 9(7): 1829-1839, 2018 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-29697951

RESUMO

4-Methylamphetamine (4-MA) is an emerging drug of abuse that acts as a substrate at plasma membrane transporters for dopamine (DAT), norepinephrine (NET), and serotonin (SERT), thereby causing nonexocytotic release of monoamine transmitters via reverse transport. Prior studies by us showed that increasing the N-alkyl chain length of N-substituted 4-MA analogues converts 4-MA from a transportable substrate (i.e., releaser) at DAT and NET to a nontransported blocker at these sites. Here, we studied the effects of the individual optical isomers of N-methyl-, N-ethyl-, and N- n-propyl 4-MA on monoamine transporters and abuse-related behavior in rats because action/function might be related to stereochemistry. Uptake inhibition and release assays were conducted in rat brain synaptosomes whereas electrophysiological assessments of drug-transporter interactions were examined using cell-based biosensors. Intracranial-self-stimulation in rats was employed to assess abuse potential in vivo. The experimental evidence demonstrates that S(+) N-methyl 4-MA is a potent and efficacious releaser at DAT, NET, and SERT with the highest abuse potential among the test drugs, whereas R(-) N-methyl 4-MA is a less potent releaser with reduced abuse potential. The S(+)ethyl analogue has decreased efficacy as a releaser at DAT but retains full release activity at NET and SERT with a reduction in abuse-related effects; the R(-)ethyl analogue has a similar profile but is less potent. S(+) N-Propyl 4-MA is a nontransported blocker at DAT and NET but an efficacious releaser at SERT, whereas the R enantiomer is almost inactive. In conclusion, the S enantiomers of the N-alkyl 4-MA analogues are most potent. Lengthening the N-alkyl chain converts compounds from potent nonselective releasers showing abuse-related effects to more selective SERT releasers with no apparent abuse potential.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/metabolismo , Fármacos do Sistema Nervoso Central/química , Fármacos do Sistema Nervoso Central/farmacologia , Metanfetamina/química , Metanfetamina/farmacologia , Simportadores/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Cálcio/metabolismo , Fármacos do Sistema Nervoso Central/síntese química , Modelos Animais de Doenças , Células HEK293 , Humanos , Isomerismo , Masculino , Metanfetamina/síntese química , Estrutura Molecular , Ratos Sprague-Dawley , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo
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