Methamphetamine (METH) abuse is a serious public health issue. Of particular concern are findings that repeated highdose administrations of METH cause persistent dopaminergic deficits in rodents, nonhuman primates, and humans. Previous studies have also revealed that METH treatment causes alterations in the dopamine transporter (DAT), including the formation of higher molecular mass DAT-associated complexes. The current study extends these findings by examining mechanisms underlying DAT complex formation. The association among DAT complex formation and other METH-induced phenomena, including alterations in vesicular monoamine transporter 2 (VMAT2) immunoreactivity, astrocytic activation [as assessed by increased glial fibrillary acidic protein (GFAP) immunoreactivity], and persistent dopaminergic deficits was also explored. Results revealed that METH-induced DAT complex formation and reductions in VMAT2 immunoreactivity precede increases in GFAP immunoreactivity. Furthermore, and as reported previously for DAT complexes, pretreatment with the D2 receptor antagonist eticlopride [S-(Ϫ)-3-chloro-5-ethyl-N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-hydroxy-2-methoxybenzamide hydrochloride] attenuated the decrease in VMAT2 immunoreactivity as assessed 24 h after METH treatment. DAT complexes distinct from those present 24 h after METH treatment, decreases in VMAT2 immunoreactivity, and increased GFAP immunoreactivity were present 48 to 72 h after METH treatment. Pretreatment with eticlopride attenuated each of these phenomena. Finally, DAT complexes were present 7 days after METH treatment, a time point at which VMAT2 and DAT monomer immunoreactivity were also reduced. Eticlopride pretreatment attenuated each of these phenomena. These findings provide novel insight into not only receptor-mediated mechanisms underlying the effects of METH but also the interaction among factors that probably are associated with the persistent dopaminergic deficits caused by the stimulant.

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BackgroundIncisional hernia is a common complication following visceral organ transplantation. Transplant patients are at increased risk of primary and recurrent hernias due to chronic immune suppression and large incisions. We conducted a retrospective review of patients with a history of liver or kidney transplantation who underwent hernia repair to analyze outcomes and hernia recurrence.MethodsThis is a single center, retrospective review of 19 patients who received kidney and/or liver transplantation prior to presenting with an incisional hernia from 2011 to 2017. All hernias were repaired with open component separation technique (CST) with biologic mesh underlay.ResultsThe mean age of patients was 61.0±8.3 years old, with a mean body mass index of 28.4±4.8 kg/m2, 15 males (78.9%), and four females (21.1%). There were seven kidney, 11 liver, and one combined liver and kidney transplant patients. The most common comorbidities were hypertension (16 patients, 84.2%), diabetes (9 patients, 47.4%), and tobacco use (8 patients, 42.1%). Complications occurred in six patients (31.6%) including hematoma (1/19), abscess (1/19), seroma (2/19), and hernia recurrence (3/19) at mean follow-up of 28.7±22.8 months. With the exception of two patients with incomplete follow-up, all patients healed at a median time of 27 days.ConclusionsThis small, retrospective series of complex open CST in transplant patients shows acceptable rates of long-term hernia recurrence and healing. By using a multidisciplinary approach for abdominal wall reconstruction, we believe that modified open CST with biologic mesh is a safe and effective technique in the transplant population with complex abdominal hernias.

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Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent (i.e., postnatal day (PND) 40) rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a “challenge” high-dose METH regimen when administered at PND90. Mechanisms underlying this “resistance” were thus investigated. Results revealed that biweekly METH treatment throughout development attenuated both the acute and persistent deficits in VMAT2 function, as well as the acute hyperthermia, caused by a challenge METH treatment. Pharmacokinetic alterations did not appear to contribute to the protection afforded by the biweekly treatment. Maintenance of METH-induced hyperthermia abolished the protection against both the acute and persistent VMAT2-associated deficits suggesting that alterations in thermoregulation were caused by exposure of rats to METH during development. These findings suggest METH during development prevents METH-induced hyperthermia and the consequent METH-related neurotoxicity.