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1.
J Sex Med ; 17(10): 2077-2083, 2020 10.
Article in English | MEDLINE | ID: mdl-32807707

ABSTRACT

BACKGROUND: Modern-day penile prostheses use infection retardant coating to decrease rates of postoperative infection, subsequently reducing explantation and revision rates as well. The Coloplast Titan models are dipped into antimicrobial solutions right before implantation, and the components used for dipping can be tailored toward the patient. AIM: To compare infection, explantation, and revision rates among different dipping solutions used before implantation for patients with diabetes receiving a Coloplast Titan implant. METHODS: We systematically reviewed 932 patients with diabetes receiving a primary penile implant across 18 different centers from the period April 2003 to August 2018. Of those patients, 473 received a Coloplast device, whereas 459 received an AMS device. Data regarding the type of antimicrobial solution used before implantation were recorded for 468 patients receiving a Coloplast Titan, including whether or not they suffered a postoperative infection and if they underwent explantation and/or revision. Outcome rates were compared using Fisher's exact and Pearson's chi-square tests, and logistic regression modeling was performed to account for covariates. OUTCOMES: The main outcome measures of this study were postoperative infection, explantation, and revision rates. RESULTS: Of the total 932 patients reviewed, 33 suffered a postoperative infection. Of 468 patients receiving Coloplast implants, there was a 3.4% infection rate. The most commonly used antibiotic combination before dipping was vancomycin + gentamicin (59.0%). There was a significantly lower rate of postoperative infection, explantation, and revision when vancomycin + gentamicin was used than those associated with the use of all other dipping solutions ([1.4% vs 6.4%; P = .004], [1.1% vs 8.3%; P < .001], and [2.5% vs 12.5; P < .001], respectively). After adjusting for age, body mass index, preoperative blood glucose level, and hemoglobin A1c, the use of other dips was an independent predictor of postoperative infection (odds ratio: 0.191; P = .049). The inclusion of rifampin in the dipping solution trended toward being a significant risk factor for infection (P = .057). Including antifungals in the dipping solution did not affect infection (P = .414), explantation (P = .421), or revision (P = .328) rates. CLINICAL IMPLICATIONS: Vancomycin + gentamicin was the most efficacious combination of antibiotics used for dipping in terms of preventing postoperative infection and subsequent explantation and revision. STRENGTHS AND LIMITATIONS: Data were sampled across multiple institutions providing a large sample that may be more representative of the population of interest. A key limitation of the study was its retrospective nature, which prevented us from controlling certain variables. CONCLUSION: The use of rifampin did not provide the same type of protection, possibly representing a shift in resistance patterns of common bacteria responsible for device infection. Towe M, Huynh LM, Osman MM, et al. Impact of Antimicrobial Dipping Solutions on Postoperative Infection Rates in Patients With Diabetes Undergoing Primary Insertion of a Coloplast Titan Inflatable Penile Prosthesis. J Sex Med 2020;17:2077-2083.


Subject(s)
Diabetes Mellitus , Penile Implantation , Penile Prosthesis , Diabetes Mellitus/drug therapy , Gentamicins/therapeutic use , Humans , Male , Retrospective Studies
2.
Transl Androl Urol ; 10(10): 3873-3884, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34804829

ABSTRACT

OBJECTIVE: We aim to review and summarize published literature that features implanted penile devices and details infection of these devices as a complication. In particular, we will detail the factors that influence infection of penile implants. BACKGROUND: Types of penile prostheses (PP) include inflatable implants and semirigid implants; these are utilized for treatment of erectile dysfunction. Likely the most feared complication of penile implants is infection. There are a handful of factors that are implicated in device infection. METHODS: Searches were performed using MEDLINE and PubMed databases using keywords and phrases 'penile implant AND infection'; 'penile prosthesis AND infection'; 'penile implant infection'. We have presented results from our literature search. We divided these into 'Surgical Elements' and 'Patient Selection and Factors.' Each topic is discussed in its own section. CONCLUSIONS: Strides have been made since the initial penile prosthesis (IPP) surgeries to improve infection rates including diabetes control, antibiotic coating of devices, and antibiotic implementation. Going forward, more studies, especially randomized control trials, need to focus on defining levels of diabetic control (sugar control and A1C control), determining the role of metabolic syndrome in infection promotion and determining laboratory values which could be predictive of infection. We present a discussion of important factors to consider in the realm of PP infections. In addition, we include studies which discuss topics for future directions in decreasing the number of infections seen with PP.

3.
J Laparoendosc Adv Surg Tech A ; 31(2): 189-193, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32584655

ABSTRACT

Background: The risk of renal cell carcinoma (RCC) development in the native kidney of patients on dialysis or with a renal transplant is increased compared to the general population. This study examines perioperative outcomes of laparoscopic radical nephrectomy (LN) in dialysis patients or renal transplant patients compared to normal controls. Methods: Four hundred twelve consecutive LN were evaluated (July 2007 to October 2018). Patients were divided into three groups (control, dialysis, and transplant). Perioperative outcomes, including operating room time (OT), postoperative complications, hospital length of stay, and 90-day readmission rates, were evaluated for the three groups. Results: There were 62 patients in the dialysis group, 20 renal transplants, and 330 normal controls. Dialysis patients were younger (median: 58 years versus 67 years; P = .002) and predominantly male (73% versus 59%, P = .047). Dialysis patients compared to controls had shorter total OT (median: 133 versus 149; P = .022), more papillary RCC (27% versus 10%; P < .001), and fewer high grade tumors (73% [8/11] versus 94% [100/106]; P = .038). Renal transplant patients had a higher rate of 90-day readmission (20% versus 6%; P = .034) and more papillary RCC (30% versus 10%; P = .016) compared to controls. Conclusion: LN on dialysis patients does not alter expected perioperative outcomes compared to a large cohort of control LN. LN on renal transplant patients carries a higher 90-day readmission rate than control LN.


Subject(s)
Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Kidney Transplantation , Renal Dialysis , Adult , Aged , Female , Humans , Laparoscopy/adverse effects , Male , Middle Aged , Nephrectomy/adverse effects , Postoperative Complications/etiology , Retrospective Studies
4.
Urology ; 152: 42-51, 2021 06.
Article in English | MEDLINE | ID: mdl-33548247

ABSTRACT

OBJECTIVE: To elucidate factors influencing Inflatable Penile Prosthesis (IPP) revision and describe outcomes associated with revision surgery. METHODS: A single surgeon, retrospective review of all patients who underwent IPP revision between 2008-2016, was performed. Patient age, BMI, operative duration, blood loss, hospital duration, time from most recent penile implant to revision surgery, etiology of revision, and whether the patient had a prior failed revision surgery were all collected and analyzed. RESULTS: A total of 57 patients, who had undergone IPP revision between the years 2008-2016, with at least 3 years of follow-up, were included in the investigation. Mean patient age and BMI were 68 and 29.2 kg/m2, respectively. The mean time between the most recent implant operation to revision was 8.4 years. Four patients (7%) reported IPP revision failure within a 3-year follow-up period. CONCLUSION: IPP revision demonstrates a relatively high success rate, in the short term, and should be offered to patients as a safe and effective option.


Subject(s)
Penile Implantation , Penile Prosthesis , Reoperation , Aged , Humans , Male , Prosthesis Design , Retrospective Studies
5.
Front Surg ; 8: 652524, 2021.
Article in English | MEDLINE | ID: mdl-33937316

ABSTRACT

Background: To evaluate robotic-assisted partial nephrectomy (RAPN) renal outcomes associated with ancillary pathology findings in non-neoplastic renal parenchymal tissue. Methods: Tissue samples from 378 RAPNs were analyzed for glomerular disease (GD), vascular disease (VD), and tubulointerstitial disease (TD). One hundred and fifty-two patients were excluded due to insufficient non-neoplastic tissue for analysis and 4 patients were excluded due to calyceal diverticulum. Non-neoplastic tissue was evaluated for GD (negative, moderate, or global), VD (absent, mild, moderate, or severe), and TD (present or absent). Associations of ancillary pathology factors with patient characteristics were explored using the non-parametric Kendall tau-test and propensity score adjusted longitudinal mixed effects regression models were used to evaluate associations of these pathology factors with changes in estimated glomerular filtration rate (eGFR) following RAPN. Results: One hundred and fifty-three (68.9%) patients had hypertension and 50 (22.5%) patients had diabetes. The majority of patients did not have any GD (N = 158, 71.2%) or TD (N = 186, 83.8%) while 129 (58.1%) had VD. VD was categorized as absent (N = 93, 41.9%), mild (N = 45, 20.3%), moderate (N = 76, 34.2%), and severe (N = 8, 6.8%). Older age (P = 0.018), hypertension (P < 0.001), and high grade MAP score (P = 0.047) were associated with a higher number of ancillary pathology factors. High grade MAP score (P = 0.03, P = 0.002) and hypertension (P = 0.02, P < 0.001) were individually associated with GD severity and VD severity, respectively. Older age was also individually associated with VD severity (P = 0.002) and hypertension was associated with TD (P = 0.04). Moderate-to-severe VD was associated with a worse change in eGFR from pre-RAPN to 1-month post-RAPN compared to those with mild or no VD (difference in mean change, -3.4 ml/kg/1.73m2; 95% CI, -6.6 to -0.2 ml/kg/1.73m2; P = 0.036). Conclusions: Moderate-to-severe VD in non-neoplastic renal parenchyma is associated with post-operative changes in eGFR. Older age, hypertension, and high grade MAP scores are associated with the number of ancillary pathologies observed in RAPN specimens.

6.
Int J Impot Res ; 33(3): 296-302, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32203432

ABSTRACT

Defining the risks associated with diabetes mellitus in patients undergoing penile prosthesis implantation remains controversial. Our study aims to assess whether preoperative hemoglobin a1c and preoperative blood glucose levels are associated with an increased risk for postoperative infection in diabetic men. We performed a retrospective review of 932 diabetic patients undergoing primary penile prosthesis implantation from 18 high-volume penile prosthesis implantation surgeons throughout the United States, Germany, Belgium, and South Korea. Preoperative hemoglobin a1c and blood glucose levels within 6 h of surgery were collected and assessed in univariate and multivariate models for correlation with postoperative infection, revision, and explantation rates. The primary outcome is postoperative infection and the secondary outcomes are postoperative revision and explantation. In all, 875 patients were included in the final analysis. There were no associations between preoperative blood glucose levels or hemoglobin a1c levels and postoperative infection rates; p = 0.220 and p = 0.598, respectively. On multivariate analysis, a history of diabetes-related complications was a significant predictor of higher revision rates (p = 0.034), but was nonsignificant for infection or explantation rates. We conclude preoperative blood glucose levels and hemoglobin a1c levels are not associated with an increased risk for postoperative infection, revision, or explantation in diabetic men undergoing penile prosthesis implantation.


Subject(s)
Diabetes Mellitus , Penile Implantation , Penile Prosthesis , Belgium , Blood Glucose , Diabetes Mellitus/epidemiology , Germany , Glycated Hemoglobin/analysis , Humans , Male , Penile Implantation/adverse effects , Penile Prosthesis/adverse effects , Postoperative Complications , Republic of Korea , Retrospective Studies , United States
7.
Urology ; 145: 258-261, 2020 11.
Article in English | MEDLINE | ID: mdl-32828870

ABSTRACT

OBJECTIVE: To determine if there is an association between patient body habitus as measured by body mass index (BMI), body surface area (BSA), preoperative prostate volume, postoperative specimen weight, and open conversion with cystotomy or perineal urethrotomy (PU) during holmium laser enucleation of the prostate (HoLEP). We attempt to provide meaningful criteria to assist in preoperative patient counseling. MATERIALS AND METHODS: Three hundred consecutive patients underwent HoLEP between August 3, 2018 and February 20, 2020 by a single surgeon. Patient metrics were recorded in a database including age, height, weight, preoperative prostate volume, postoperative specimen weight, catheter dependence, and transfusion requirement. Nine patients were identified who had cystotomy (8) or PU (1) performed during HoLEP secondary to inability to complete the procedure using standard endoscopic technique. Univariate and multivariate statistical analysis was performed. RESULT: Younger age, higher BMI, higher BSA, and higher estimated prostate volume were associated with increased risk of open conversion during HoLEP. No patient with a BMI under 30 required open conversion. CONCLUSION: Men with BMI >30 kg/m2 or preoperative prostate volume >125 mL should be counseled on the possibility of open conversion with cystotomy or PU. Although the overall risk of conversion is low (3%), the risk may be as high as 10% for patients in the highest quartile of BMI (>30.5 kg/m2) and BSA (>2.2m2).


Subject(s)
Conversion to Open Surgery , Cystotomy/adverse effects , Endoscopy/adverse effects , Lasers, Solid-State/therapeutic use , Prostatic Hyperplasia/surgery , Urethra/surgery , Aged , Aged, 80 and over , Body Mass Index , Body Surface Area , Humans , Male , Middle Aged , Organ Size , Retrospective Studies , Risk Factors
8.
Urology ; 145: 141-146, 2020 11.
Article in English | MEDLINE | ID: mdl-32958224

ABSTRACT

OBJECTIVES: To evaluate the association between excised parenchymal mass (EPM) and postoperative renal function (eGFR) following robotic-assisted partial nephrectomy (RAPN). EPM is the amount of healthy renal parenchyma excised during partial nephrectomy in order to achieve safe surgical margins. METHODS: We evaluated 406 consecutive RAPN performed by a single surgeon to eliminate variations in technique as a factor in EPM. EPM (mL) = (specimen volume * π/6) - (tumor volume * π/6). RENAL score was categorized as easy (4-6), moderate (7-9), or hard (10-12). EPM was grouped into four categories: ≤ 3.9 mL, 4.0-9.9 mL, 10.0-17.7 mL, and >17.7 mL. eGFR was evaluated preoperatively, postoperative day 1 (POD1), 1 month, and 6 months postoperatively. RESULTS: Median age was 63 years (22-84 years), 252 (62.1%) were male, and median EPM was 9.9 mL (interquartile range 3.9 to 17.7 mL). The median EPM and interquartile range for each RENAL category was 3.7 mL (2.0, 7.9), 12 mL (5.7, 19.4), and 16.2 mL (7.9, 24.3), respectively. Higher EPM was associated with worse changes in eGFR at POD1 (P = 0.005) and 1 month after RAPN (P = 0.002) but was not statistically significant at the 6-month time period (P = 0.35) CONCLUSION: Increased tumor complexity is associated with an increase in EPM during RAPN. Increased EPM is associated with eGFR decline at POD1 and 1 month post RAPN but not at 6 months postoperatively.


Subject(s)
Kidney Neoplasms/surgery , Kidney/pathology , Nephrectomy/adverse effects , Postoperative Complications/epidemiology , Robotic Surgical Procedures/adverse effects , Adult , Aged , Aged, 80 and over , Female , Glomerular Filtration Rate/physiology , Humans , Kidney/physiopathology , Kidney/surgery , Kidney Neoplasms/pathology , Male , Margins of Excision , Middle Aged , Nephrectomy/methods , Postoperative Complications/etiology , Postoperative Complications/physiopathology , Retrospective Studies , Risk Assessment/methods , Robotic Surgical Procedures/methods , Tumor Burden , Young Adult
9.
Urology ; 138: 125-128, 2020 04.
Article in English | MEDLINE | ID: mdl-31978525

ABSTRACT

OBJECTIVE: To determine if preoperative catheter dependence or specimen weight is associated with failed trial without catheter (TWOC) following holmium laser enucleation of the prostate (HoLEP). MATERIAL AND METHODS: The study population consisted of 143 consecutive men who underwent HoLEP by a single surgeon over 10 months. Ten were excluded from analysis because they did not have a TWOC on the morning following surgery. Preoperative catheter dependence and specimen weight as well as catheter reinsertions were analyzed. RESULTS: Of 133 men included in analysis, 23 (17.3%) required catheter reinsertion. Of the 23 requiring catheter reinsertion, 6 were catheter dependent preoperatively and 17 were not. Men who were catheter dependent had a lower overall rate of failed TWOC compared to those who were not catheter dependent (15.0% vs 18.3%, P = .647). Mean specimen weight for men requiring catheter reinsertion was significantly lower than men who passed their TWOC (49.9 gm vs 73.1 gm, P = .013). CONCLUSION: Very few studies exist on factors associated with short-term catheter reinsertion following HoLEP or other prostatic hyperplasia procedures. We hypothesized that preoperative catheter dependence and small specimen weight would predispose to catheter reinsertion. Specimen weight was inversely related to risk of catheter reinsertion after HoLEP and preoperative catheter dependence was not associated with catheter reinsertion. In men with small prostates, consideration should be given to delayed TWOC to allow resolution of capsular edema and accumulation of clot in the prostatic fossa. Transition zone volume below which delayed TWOC should be considered is the subject of future studies.


Subject(s)
Lasers, Solid-State/adverse effects , Postoperative Complications/therapy , Prostatectomy/adverse effects , Prostatic Hyperplasia/therapy , Urinary Catheterization/statistics & numerical data , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Postoperative Complications/etiology , Prostate/pathology , Prostate/surgery , Prostatectomy/instrumentation , Prostatectomy/methods , Prostatic Hyperplasia/pathology , Retrospective Studies , Treatment Outcome , Urinary Catheters
10.
Urology ; 144: 136-141, 2020 10.
Article in English | MEDLINE | ID: mdl-32619599

ABSTRACT

OBJECTIVES: To evaluate the learning curve of robotic-assisted partial nephrectomy as it pertains to operative time (OT) and advanced perioperative variables such as achievement of trifecta, postoperative complications, 30-day readmission rates (RR), warm ischemia time (WIT), and functional volume loss (FVL). METHODS: We evaluated 418 consecutive robotic-assisted partial nephrectomy performed by a single surgeon between February 2008 and April 2019. Multivariable log-log regression models were used to evaluate the associations between case number and continuous outcomes (OT, WIT, and FVL). Multivariable logistic regression models were used to evaluate the association of case number with dichotomous outcomes (trifecta, postoperative complications, RR). RESULTS: Among the 406 eligible patients included in the study, 252 (62.1%) were male, median age was 63 years (range, 22-84), and median body mass index was 29 kg/m2 (interquartile range 26-33). Surgeon experience was associated with shorter OT (-2.5% per 50% increase in case number; 95% confidence interval; P <.001) and plateaus around 77 cases performed. There was slight improvement with trifecta (odds ratio [per 50% increase in cases] = 1.08; 95% confidence interval) and the plateau was also at 77 cases, however, this was not statistically significant (P = .086). We did not find statistically significant associations of surgeon experience with FVL (P = .77), postoperative complications (P = .74), WIT (P = .73), or 30-day RR (P = .33). CONCLUSION: There does not appear to be a relationship between surgical experience and grade 3 or higher postoperative complications, 30-day RR, WIT, or FVL. Trifecta outcomes and maximum OT performance appear to be optimized at approximately 77 cases.


Subject(s)
Kidney Neoplasms/surgery , Learning Curve , Nephrectomy/adverse effects , Postoperative Complications/epidemiology , Robotic Surgical Procedures/adverse effects , Aged , Clinical Competence/statistics & numerical data , Female , Humans , Male , Middle Aged , Nephrectomy/education , Nephrectomy/methods , Postoperative Complications/etiology , Retrospective Studies , Robotic Surgical Procedures/education , Robotic Surgical Procedures/methods , Surgeons/education , Surgeons/statistics & numerical data , Treatment Outcome , Urologists/education , Urologists/statistics & numerical data , Warm Ischemia/adverse effects
11.
Urology ; 132: 212, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31271781

ABSTRACT

OBJECTIVE: To demonstrate the surgical considerations for managing retained UroLift implants when performing HOLEP. Prostatic Urethral Lift via the UroLift System has become a common treatment modality to manage symptoms associated with benign prostatic hyperplasia. The UroLift procedure uses nonabsorbable implants to retract obstructing prostate lobes. Retreatment rates following UroLift have been reported at 13.6% over 5 years.1 We anticipate an increasing number of men seeking definitive surgical management after failed UroLift. There have been reports in the literature of UroLift implants causing morcellator device jams when attempting holmium laser enucleation of the prostate (HOLEP).2 METHODS: From August 2018 to April 2019, we reviewed 118 consecutive patients who underwent HOLEP by a single surgeon. Three men were identified who had previously undergone UroLift. Video footage was obtained. As demonstrated in the video, during enucleation, the metallic clip of the UroLift implants were incorporated in the adenoma specimen. For morcellation, we use the Piranha morcellator (Richard Wolf, Knittlingen, Germany). Morcellation was carried out in a slow and controlled manner. When the metal clip comes into contact with the morcellator, a catch and release is performed by releasing the morcellator pedal and withdrawing the morcellator into the nephroscope to release the adenoma. Remnant clips and sutures can be retrieved with a grasper. We perform a 3 month follow-up cystoscopy in the office to exclude any remnant implant material in the prostatic urethra or bladder. RESULTS: Procedures were completed uneventfully. In developing this technique, we experienced jamming of the morcellator blades in 2 cases requiring replacement of the disposable blades. Follow up in-office cystoscopy did not reveal any remnant implant material that needed to be removed. CONCLUSION: HOLEP can be performed safely in the UroLift failure patient population. Careful morcellation techniques can decrease the risk of costly morcellator blade replacement.


Subject(s)
Laser Therapy , Lasers, Solid-State/therapeutic use , Prostatectomy/methods , Prostatic Hyperplasia/surgery , Prostheses and Implants , Humans , Male , Treatment Failure , Urologic Surgical Procedures
12.
J Neuroimmune Pharmacol ; 11(4): 669-679, 2016 12.
Article in English | MEDLINE | ID: mdl-27287619

ABSTRACT

The spleen is a visceral organ that contracts during hypoxia to expel erythrocytes and immune cells into the circulation. Spleen contraction is under the control of noradrenergic sympathetic innervation. The activity of noradrenergic neurons terminating in the spleen capsule is regulated by α2-adrenergic receptors (AR). Interactions between endogenous cannabinoid signaling and noradrenergic signaling in other organ systems suggest endocannabinoids might also regulate spleen contraction. Spleens from mice congenitally lacking both CB1 and CB2 cannabinoid receptors (Cnr1 -/- /Cnr2 -/- mice) were used to explore the role of endocannabinoids in spleen contraction. Spleen contraction in response to exogenous norepinephrine (NE) was found to be significantly lower in Cnr1 -/- /Cnr2 -/- mouse spleens, likely due to decreased expression of capsular α1AR. The majority of splenic Cnr1 mRNA expression is by cells of the spleen capsule, suggestive of post-synaptic CB1 receptor signaling. Thus, these studies demonstrate a role for CB1 and/or CB2 in noradrenergic splenic contraction.


Subject(s)
Adrenergic Neurons/metabolism , Receptor, Cannabinoid, CB1/deficiency , Receptor, Cannabinoid, CB2/deficiency , Spleen/innervation , Spleen/metabolism , Adrenergic Neurons/drug effects , Animals , Female , Isometric Contraction/drug effects , Isometric Contraction/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Norepinephrine/pharmacology , Organ Culture Techniques , Spleen/drug effects
13.
Neurotoxicology ; 37: 144-53, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23643664

ABSTRACT

Hypothalamic tuberoinfundibular dopamine (TIDA) neurons remain unaffected in Parkinson disease (PD) while there is significant degeneration of midbrain nigrostriatal dopamine (NSDA) neurons. A similar pattern of susceptibility is observed following acute exposure to the neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and the resistance of TIDA neurons to MPTP is associated with increased expression of parkin and ubiquitin carboxy-terminal hydrolase L-1 (UCHL-1). In the present study, the response of TIDA and NSDA neurons to acute MPTP administration following chronic MPTP exposure was examined. Mice were treated with ten injections of either MPTP (20mg/kg; s.c.; every 3.5 days) or saline vehicle (10 ml/kg; s.c.; every 3.5 days). Following a 21 day recovery period, chronic saline- and MPTP-treated mice received an additional injection of either saline (10 ml/kg; s.c.) or MPTP (20mg/kg; s.c.) and were sacrificed 24h later. NSDA neurons displayed significant axon terminal degeneration (as reflected by decreases in DA, tyrosine hydroxylase (TH) and DA transporter concentrations in the striatum) as well as loss of TH-immunoreactive (IR) neurons in the substantia nigra (SN) following MPTP, whereas TIDA neurons revealed no overt axon terminal pathology or loss of TH-IR cell bodies. NSDA neuronal pathology was associated with transient decreases in concentrations of parkin and UCHL-1 protein in the SN, which returned to normal levels by 21 days following cessation of chronic neurotoxicant exposure. Resistance of TIDA neurons to MPTP toxicity was correlated with a transient increase in UCHL-1 and a sustained elevation in parkin in the arcuate nucleus. TIDA neurons represent a DA neuron population with a unique and inherent ability to adapt to acute and chronic toxicant administration with a sustained elevation of the neuroprotective protein parkin. The correlation between the ability to increase parkin and UCHL-1 expression and the resistance of DA neurons to neurotoxicant exposure is consistent with a functional link between these features and an underlying differential susceptibility to toxicant-associated neurodegeneration.


Subject(s)
Dopamine/metabolism , Dopaminergic Neurons/metabolism , Hypothalamus/metabolism , MPTP Poisoning/metabolism , Ubiquitin-Protein Ligases/metabolism , Animals , Disease Models, Animal , Dopamine Plasma Membrane Transport Proteins/metabolism , Dopaminergic Neurons/pathology , MPTP Poisoning/etiology , MPTP Poisoning/pathology , Male , Mesencephalon/metabolism , Mesencephalon/pathology , Mice , Mice, Inbred C57BL , Nerve Degeneration , Time Factors , Tyrosine 3-Monooxygenase/metabolism , Ubiquitin Thiolesterase/metabolism , Up-Regulation
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