[Clinical analysis of adult oculomoclonus-myoclonus syndrome with vertigo].

The clinical manifestation, physical and laboratory examination, electrophysiological, and imaging data of 2 female adult OMS patients with vertigo were analyzed at the Department of Neurology of the First Medical Center of Chinese PLA General Hospital from February 2021 to March 2022. The treatment strategy and clinical outcome were followed up. The two female patients were aged 42 and 66 years. Anti-NMDA receptor antibody and anti-GABAB receptor antibody were detected in serological screening, respectively. The two patients met the diagnostic criteria for OMS, and one was screened for breast tumor. The clinical symptoms of the two patients were relieved after immunomodulation therapy. OMS is a group of rare clinical syndromes; its clinical evaluation process should be standardized and the etiology should be actively searched for.

[Association between cardiometabolic diseases and quality of life and the mediation effect of perceived stress].

Objective: To explore the association between cardiometabolic diseases (CMD) and quality of life, the association between CMD and perceived stress, and the mediation effect of perceived stress on the association between CMD and quality of life, and to provide evidence for the prevention and treatment of CMD and the improvement of quality of life in these patients. Methods: This is a cross-sectional study. Data were collected by the employees' physical examination of a company in Xi'an in 2021. Multiple linear regression models were used to analyze the association between the status of CMD (divided into three categories: no CMD, presence of one kind of CMD, and with≥2 kinds of CMD (≥2 kinds of CMD were defined as cardiometabolic multimorbidity (CMM)), quality of life, and perceived stress. Mediation analysis with a multi-categorical independent variable was conducted to determine the mediation effect of perceived stress on the association between CMD and quality of life. Results: Among all 4 272 participants, 1 457 (34.1%) participants had one kind of CMD and 677 (15.8%) participants had CMM. The average scores for quality of life and perceived stress were (57.5±15.7) and (16.9±7.9), respectively. Compared with participants without CMD, after adjusting for demographic and lifestyle factors, no statistically significant associations were observed between one kind of CMD and perceived stress or quality of life (both P>0.05). Perceived stress did not mediate the association between one kind of CMD and quality of life. However, participants with CMM had lower quality of life and higher perceived stress than participants without CMD. The relative total effect coefficient c (95%CI) and the relative direct effect coefficient c' (95%CI) between CMM and quality of life were -3.71 (-5.04--2.37) and -2.52 (-3.81--1.24) (both P<0.05), respectively. The relative indirect effect coefficient a2b (95%CI) of perceived stress on the association between CMM and quality of life was -1.18 (-1.62--0.77) (P<0.05). The mediation effect size was 31.8%. Conclusions: CMM is negatively associated with quality of life and positively associated with perceived stress. Perceived stress partially mediates the association between CMM and quality of life. Our results suggest that, in addition to preventing and treating CMM actively, efforts should be taken to relieve the perceived stress of people with CMM to improve their quality of life.

[Efficacy and safety of barbed sutures in total hip arthroplasty and total knee arthroplasty: a meta-analysis].

Objective: To appraise the clinical outcomes of barbed suture in closure of total hip and total knee arthroplasty. Methods: Databases (Web of Science, Embase, PubMed, Cochrane Controlled Trials Register,Cochrane Library,Highwire,China Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI),VIP and Wanfang database) were searched for randomized controlled trials comparing barbed sutures and conventional sutures in total hip and total knee arthroplasty published before January, 2019. Finally, 11 articles (12 randomized controlled trials) involving 1 629 hips or knees were included in this study. The meta-analysis was performed using the Review Manager software. Results: Compared with conventional sutures,barbed sutures resulted in shorter total wound closure time (P<0.001), less ecchymosis and needle prick (both P<0.05).There was no significant differences in terms of wound related complications, superficial infection, stitch abscess, blister, exudation, broken sutures, range of motionand KSS between barbed sutures and conventional sutures(all P>0.05). Conclusions: Based on available level Ⅰ evidence, it indicated that knotless barbed suture maybe a better approach for wound closure in total hip and total knee arthroplasty.

[Significance of pelvic contrast enhanced MRA prior to prostatic artery embolization].

Objective: To assess the values of pelvic contrast enhanced magnetic resonance angiography (MRA) in detection of prostatic artery prior to prostatic arterial embolization(PAE). Methods: This multicenter, prospective study from 5 hospitals in China consisted of 47 patients (mean age (69±16) years, range 56-83 years) who underwent PAE for benign prostatic hyperplasia (BPH) between January 2016 and April 2018, preprocedural prediction of prostatic arteries were determined using contrast enhanced MRA.CE-MRA findings were compared with subsequent intraprocedural digital subtraction angiography (DSA) or DSA combined with cone-beam computed tomography (CT) to assess the sensitivity and specificity with which contrast enhanced MRA predicted the number and origins of prostatic artery, also to assess the optimal oblique projection of PA. Results: In total, 47 patients (94 pelvic sides) with 97 PAs confirmed by DSA or DSA combined with cone-beam CT at the time of embolization, MR angiography successfully identified 88 PAs and their origins , the sensitivity and specificity was 90.7% (88/97) and 93.6% (88/94), respectively.MR angiography correctly determined the bilateral prostatic artery origins in 36 (76.6%) cases.According to the optimal oblique projection of PAs suggested by MR angiography, the origins and trajectory of PAs of all patients underwent PAE with the same oblique projection (20°-45°ipsilateral anterior oblique direction) were clearly displayed when performed the first arteriography. Conclusion: Pelvic contrast enhanced MR angiography with high sensitivity and specificity in detection the origin, trajectory and number of PAs, and it could provide useful information regarding prostatic arteries before PAE.

Combination of LINE-1 hypomethylation and RASSF1A promoter hypermethylation in serum DNA is a non-invasion prognostic biomarker for early recurrence of hepatocellular carcinoma after curative resection.

Hepatocarcinogenesis, a multistep process, involves not only genetic mutations but also epigenetic alterations. Widespread of global DNA hypomethylation is accompanied with specific regional hypermethylation especially at tumor suppressor genes' promoters. The aim of this study is to determine the efficacy of combined DNA methylation analysis of a global DNA methylation marker - LINE-1 and a tumor suppressor gene highly associated with the malignancy of HCC- RASSF1A in serum as a novel prognostic marker for diagnosis of early recurrence after curative resection.LINE-1 was hypomethylated in 66.7% (70/105) and RASSF1A promoter was hypermethylated in 73.3% (77/105) of HCC serum DNA samples by methylation specific PCR, but in none of the healthy controls: LINE-1 hypometylation (0/50) and RASSF1A hypermethylation (0/50). A significant association was found between LINE-1 hypomethylation and clinical pathologic features including HBsAg positivity (p=0.009), tumor size (p=0.001) and AFP levels (p<0.001). Besides, significant correlation was detected between RASSF1A promoter hypermethylation and lymph nodes metastasis (p=0.045).The results of Kaplan-Meier estimates of survival suggested that LINE-1 hypomethylation was highly associated with poor survival of patients (disease-free survival p=0.002, overall survival p=0.0123). More importantly, co-evaluation of LINE-1 hypomethylation and RASSF1A promoter hypermethylation was found to be significantly correlated to early recurrence and poor prognosis (disease-free survival p=0.0001, overall survival p=0.05) in patients after curative resection.In conclusion, our study showed that the combined examination of LINE-1 hypomethylation and RASSF1A promoter hypermethylation was effective in predicting early recurrence of HCC after curative resection. Patients with dual positivity of LINE-1 hypomethylation and RASSF1A promoter hypermethylation should be supplied with more intensive care and close follow-up after they undergo tumor resection.

[Efficacy and safety of drainage after total knee arthroplasty].

Objective: To determine whether suction drainage is safe and effective compared with no-drainage in total knee arthroplasty. Methods: The literature search was based on PubMed, MEDLINE, EMBASE, Highwire, the Cochrane Library, CBM, CNKI, VIP and WFSD.The data were analysed using RevMan 5.3.Fourteen randomised controlled trials involving 1 009 knees were included in our analysis. Results: Suction drainage increases the rate and volume of blood transfusion.No-drainage group increases the rate of wound problems (OR=1.92, 95%CI 1.21-3.04, P<0.05). No significant difference was observed in the incidence of periprosthetic infection (OR=0.68, 95%CI 0.20-2.30, P=0.54), VAS (OR=-0.09, 95%CI -0.32-0.14, P=0.46) and the length of stay (OR=0.41, 95%CI -0.21-1.03; P=0.19) when the drainage group was compared with the no-drainage group (P>0.05). Conclusions: No-drainage for easy total knee arthroplasty may be a better choice. However, orthopedic surgeon need to weigh the pros and cons of no-drainage in some complicated TKAs such as extra-articular deformity .

[Meta analysis of the efficacy and safety of drainage after total hip arthroplasty].

Objective: To determine whether suction drainage is safe and effective compared with no-drainage in total hip arthroplasty. Methods: The research was based on PubMed, MEDLINE, EMBASE, Highwire, the Cochrane Library, CBM, CNKI, VIP and WFSD.The data were analysed using RevMan 5.2.Twenty-seven randomised controlled trials involving 3 603 hips were included in the analysis. Results: The meta-analysis indicate that suction drainage increases the rate of homologous blood transfusion (OR=1.98, 95%CI: 1.49-2.64, P<0.000 01)and the length of stay (OR=0.66, 95%CI: -0.01-1.33, P=0.05) (P<0.05). No significant difference was observed in the incidence of infection(OR=0.80, 95%CI: 0.52-1.22, P=0.30), wound haematomas(OR=0.47, 95%CI: 0.21-1.10, P=0.08), oozing (OR=0.93, 95%CI: 0.63-1.36, P=0.71) , deep venous thrombosis(OR=2.12, 95%CI: 0.68-6.56, P=0.19), VAS(OR=-0.06, 95%CI: -0.37-0.24, P=0.68) when the drainage group was compared with the no-drainage group. Conclusions: The comparison between suction drainage and no drainage in THA have indicated that no-drainage for easy total hip arthroplasty may be a better choice. However, orthopedic surgeon need to weigh the pros and cons of no-drainage in some complicated THAs.

BLyS expression and JNK activation may form a feedback loop to promote survival and proliferation of multiple myeloma cells.

B-Lymphocyte stimulator (BLyS), a member of tumor necrosis factor superfamily, is a potent co-activator of B cells in vitro, and in vivo induces B cell proliferation and immunoglobulin secretion. Multiple myeloma (MM) is an incurable malignancy of terminally differentiated B cells (plasma cells). Previous studies have well ascertained that BLyS plays an important contributory role in the pathogenesis and propagation of multiple myeloma by virtue of its ability to promote B cell survival, expansion, and differentiation. However, the intracellular signaling of BLyS in human MM cells remains undefined. This study was designed to see whether there was interaction between MAPK signaling pathway and BLyS expression. It was found that the active protein p-JNK was expressed in KM3, U266 and PBMCs of MM patients, and that the expression of BLyS could be changed by JNK pathway activator and inhibitor. In addition, recombinant BLyS activated JNK pathway, while BLyS siRNA treatment inhibited the activation of JNK pathway. The level of BLyS expression and the activation of JNK pathway were positively correlated. These findings suggest that JNK activation and BLyS expression in MM cells may form a positive feedback loop that promotes the survival and proliferation of MM cells, and these may shed some light on the pathogenesis and treatment of MM.

Global variation and uniformity of eggshell thickness for chicken eggs.

Damaged eggshells result in losses of eggs. Numerous efforts have been carried out to improve eggshell quality, which may lead to increased eggshell thickness. The conventional way of enhancing eggshell strength with thicker eggshell on average may be replaced by a new strategy to improve eggshell uniformity without increasing eggshell thickness. To achieve this, it is necessary to investigate global variation of eggshell thickness. In this study, we used 100 fresh eggs from 52-wk-old layers of a commercial brown-egg variety. To determine the global variation of eggshell thickness, 42 points for each egg along both longitudinal and latitudinal axes were selected to measure thickness using an eggshell thickness gauge. The eggshell thickness from blunt to sharp end varied significantly (P < 0.05). The area surrounding the blunt end was the thinnest (0.341 ± 0.025 mm), whereas the area surrounding the sharp end was the thickest (0.367 ± 0.023 mm). It was found that the thickness of the sharp end was the closest to the average thickness of the whole eggshell and could be considered as a valid measurement of eggshell thickness. A new parameter, eggshell thickness uniformity, was defined as the reciprocal of the coefficient of variation (1/CV) of eggshell thickness from 42 points of each egg and can be used to evaluate the eggshell quality. Eggshell thickness uniformity was positively correlated with breaking strength (r = 0.341; P < 0.01), suggesting that the parameter may be used as a potential selection criterion in breeding program to improve eggshell quality without increasing eggshell thickness.

[Clinical features of 123 patients with hyperinsulinemic hypoglycemia auxiliarily diagnosed by 18F-DOPA-PET CT scanning].

Objective: To summarize the clinical features and therapeutic outcomes of patients with hyperinsulinemic hypoglycemia (HH) auxiliarily diagnosed by 18F-DOPA positron emission tomography (PET) CT scanning. Methods: The clinical data of 123 patients who were diagnosed with hyperinsulinemic hypoglycemia by comprehensive clinical diagnostic procedures in the Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University between January 2016 and December 2020 were retrospectively analyzed. Clinical data such as gender, age of onset, province, concurrent serum insulin level measured during hypoglycemia, lesion type of pancreas by 18F-DOPA-PET CT scanning, genetic test results, and treatment were collected successively. The clinical features and therapeutic outcomes were compared between patients with focal and diffuse pancreatic lesions. T test, Rank sum test, and χ² test were used for comparison between groups. Results: A total of 123 patients with hyperinsulinemic hypoglycemia (72 males and 51 females), whose average age of onset was 3 days (ranging from 1 day to 4 860 days), were recruited from 24 provinces. The concurrent serum insulin level was 7.1 (0.4-303.0) mU/L during hypoglycemia. 18F-DOPA-PET CT scanning identified focal lesions in 25.2% (31/123) and diffuse lesions in 74.8% (92/123) of the patients; 64.2% (79/123) of the HH cases were found to have pathogenic gene variants, in which 88.6% (70/79) were found to have KATP channel related genes (61 in ABCC8 and 9 in KCNJ11 mutations). Thirty-seven patients (17 focal and 20 diffuse) received surgical treatment with a success rate of 67.6% (25/37). The effective rate of diazoxide for children with diffuse type was significantly higher than that of children with focal group (28.3% (26/92) vs. 9.7% (3/31), χ²=10.31, P=0.001). Conclusions: 18F-DOPA-PET CT scan can improve the success rate of surgery. Comprehensive diagnosis of the etiology of hyperinsulinemic hypoglycemia by genetic analysis and 18F-DOPA-PET CT scanning can result in better treatment and prognosis.

Optofluidic differential colorimetry for rapid nitrite determination.

Nitrite detection plays a very important role in environmental monitoring and for industrial purposes. The commonly used colorimetric analysis requires the measurement of a system's calibration curve by asynchronously preparing and detecting a dozen standard samples, leading to time-consuming, slow and cumbersome procedures. Here, we present a differential colorimetry method that determines the nitrite level based on the paired chromaticity gradient, formed by coupling the colour reaction into the microfluidic network. The two gradients reshape each other and contain enough information for the quantitative analysis of the sample being tested, without the need for a calibration curve. The independence of the two gradients of the absorbance change caused by the detecting system and water quality results in a high stability and anti-interference performance, with the assistance of its self-correcting ability. This differential colorimetry method requires little time and energy consumption as only one sample is needed. Standard nitrite solutions of 0.50 mM and 0.33 mM have been determined with an error of 1.16% and 0.50%, respectively. These measurements are advantageous in terms of greater stability by up to 10 times and accuracy by 6 times, compared with the calibration curve approaches. It is foreseeable that this differential colorimetry method will find a wide range of applications in the field of chemical detection.

Optofluidic marine phosphate detection with enhanced absorption using a Fabry-Pérot resonator.

Real-time detection of phosphate has significant meaning in marine environmental monitoring and forecasting the occurrence of harmful algal blooms. Conventional monitoring instruments are dependent on artificial sampling and laboratory analysis. They have various shortcomings for real-time applications because of the large equipment size and high production cost, with low target selectivity and the requirement of time-consuming procedures to obtain the detection results. We propose an optofluidic miniaturized analysis chip combined with micro-resonators to achieve real-time phosphate detection. The quantitative water-soluble components are controlled by the flow rate of the phosphate solution, chromogenic agent A (ascorbic acid solution) and chromogenic agent B (12% ammonium molybdate solution, 80% concentrated sulfuric acid and 8% antimony potassium tartrate solution with a volume ratio of 80 : 18 : 2). Subsequently, an on-chip Fabry-Pérot microcavity is formed with a pair of aligned coated fiber facets. With the help of optical feedback, the absorption of phosphate can be enhanced, which can avoid the disadvantages of the macroscale absorption cells in traditional instruments. It can also overcome the difficulties of traditional instruments in terms of size, parallel processing of numerous samples and real-time monitoring, etc. The absorption cell length is shortened to 300 µm with a detection limit of 0.1 µmol L-1. The time required for detection is shortened from 20 min to 6 seconds. Predictably, microsensors based on optofluidic technology will have potential in the field of marine environmental monitoring.

Voltage-controlled interlayer coupling in perpendicularly magnetized magnetic tunnel junctions.

Magnetic interlayer coupling is one of the central phenomena in spintronics. It has been predicted that the sign of interlayer coupling can be manipulated by electric fields, instead of electric currents, thereby offering a promising low energy magnetization switching mechanism. Here we present the experimental demonstration of voltage-controlled interlayer coupling in a new perpendicular magnetic tunnel junction system with a GdOx tunnel barrier, where a large perpendicular magnetic anisotropy and a sizable tunnelling magnetoresistance have been achieved at room temperature. Owing to the interfacial nature of the magnetism, the ability to move oxygen vacancies within the barrier, and a large proximity-induced magnetization of GdOx, both the magnitude and the sign of the interlayer coupling in these junctions can be directly controlled by voltage. These results pave a new path towards achieving energy-efficient magnetization switching by controlling interlayer coupling.

Beta-platelet-derived growth factor receptor mediates motility and growth of Ewing's sarcoma cells.

The Ewing's sarcoma family of tumors (ESFT) contain a translocation, t(11;22), which results in the novel oncogenic fusion protein EWS/FLI1. Platelet-derived growth factors (PDGF) and their receptors (PDGFR) are involved in the induction and proliferation of numerous solid tumors and are the potential candidates for novel targeted antitumor therapy. Since a relation was reported between PDGF-C and EWS/FLI1, we sought to characterize the PDGF signaling pathway in ESFT. Eight out of nine ESFT cell lines were found to express significant levels of beta-PDGFR. Interestingly, none of the tested cell lines expressed alpha-PDGFR, which is the receptor isotype required for PDGF-C binding. By immunohistochemical staining 47 of 52 (90.4%) archival tumor samples from patients with ESFT were positive for beta-PDGFR. ESFT cell lines were treated with PDGF-AA or PDGF-BB ligands to evaluate downstream signaling. Autophosphorylation of beta-PDGFR and tyrosine phosphorylation of PLC-gamma, PI3Kp85 and Shc were detected only in PDGF-BB-stimulated cells that express beta-PDGFR. Receptor function was further evaluated using chemotaxis assays that showed TC-32 cell migration towards PDGF-BB. A specific PDGFR kinase inhibitor AG1295 blocked beta-PDGFR activation, downstream signaling, growth in cell culture and chemotaxis of TC-32 cells. AG1295 also delayed tumor formation and prolonged survival in an ESFT animal model. We conclude that ESFT express beta-PDGFR and that this is a functional and potentially crucial signaling pathway. Therefore, beta-PDGFRs may provide a novel therapeutic target in ESFT that can be utilized to design better treatment modalities.

Arterial embolization of massive hepatocellular carcinoma with lipiodol and gelatin sponge.

BACKGROUND: Transarterial chemoembolization (TACE) has been used to treat unresectable massive hepatocellular carcinoma (HCC). Lots of embolic agents have been applied in embolization because of it can decrease patient discomfort and side-effects. AIM: The aim was to evaluate the clinical efficacy and safety of TACE with lipiodol and gelatin sponge. MATERIALS AND METHODS: A total of 109 patients with massive HCC (the size of tumor >10 cm and unresectable) from January 2011 to August 2014 in our institution was divided into group A and group B based on the different embolitic agents. Before and about 1-month after each case of TACE, clinical and biological data such as tumor size, Child-Pugh stage, serum alpha-fetoprotein (AFP), complications, were recorded at the same time. RESULTS: In group A, the diameter of the tumor reduced from 12.57 ± 1.26 cm to 9.04 ± 0.89 cm. No patient was complete response (CR), partial response (PR) 36, stable disease (SD) 7 and PD 6; in group B, the diameter of tumor decreased from 12.08 ± 1.42 cm to 8.43 ± 1.05 cm, CR 0, but PR 27, SD 18 and PD 15. RR in group A was significantly higher than in group B (P < 0.05).The change of Child-Pugh stage and AFP pre- and post-operative in group A can be found significantly better than in group B. CONCLUSIONS: TACE with lipiodol and gelatin sponge is a highly effective for massive HCC.

Transcatheter arterial embolization of acute gastrointestinal tumor hemorrhage with Onyx.

BACKGROUND: Endovascular embolization has been used to control gastrointestinal tumor bleeding. Lots of embolic agents have been applied in embolization, but liquid embolic materials such as Onyx have been rarely used because of concerns about severe ischemic complications. AIM: To evaluate the clinical efficacy and safety of transcatheter arterial embolization (TAE) with Onyx for acute gastrointestinal tumor hemorrhage. MATERIALS AND METHODS: Between September 2011 and July 2013, nine patients were diagnosed as acute gastrointestinal tumor hemorrhage by clinical feature and imaging examination. The angiographic findings were extravasation of contrast media in the five patients. The site of hemorrhage included upper gastrointestinal bleeding in seven cases and lower gastrointestinal bleeding in two cases. TAE was performed using Onyx in all the patients, and the blood pressure and heart rate were monitored, the angiographic and clinical success rate, recurrent bleeding rate, procedure related complications and clinical outcomes were evaluated after therapy. The clinical parameters and embolization data were studied retrospectively. RESULTS: All the patients (100%) who underwent TAE with Onyx achieved complete hemostasis without rebleeding and the patients were discharged after clinical improvement without a second surgery. No one of the patients expired during the hospital course. All the patients were discharged after clinical improvement without a second surgery. Postembolization bowel ischemia or necrosis was not observed in any of the patients who received TAE with Onyx. CONCLUSIONS: TAE with Onyx is a highly effective and safe treatment modality for acute gastrointestinal tumor hemorrhage, even with pre-existing coagulopathy.

Skin fibrinolytic activity in cutaneous and systemic vasculitis.

Study of involved and uninvolved skin from patients with necrotizing vasculitis revealed diminished tissue fibrinolytic activity deposition of immunoreactants in involved skin. In these patients, the depletion of tissue fibrinolytic activity is probably the result of vessel injury secondary to the local deposit of immunoreactants. In addition, there was diminished tissue fibrinolytic activity in uninvolved skin from patients with and without clinical skin involvement, unassociated with the deposition of immunoreactants. The precise mechanism for diminished tissue lytic activity in these latter patients is not known, but it may be associated with generalized activation of the coagulation and fibrinolytic mechanisms that result in local depletion of tissue fibrinolytic activity. These local changes may aggravate the clinical course of the disease as well as inhibit the healing of the lesions.

Regulatory considerations for preclinical development of anticancer drugs.

The entry of new anticancer treatments into phase I clinical trials is ordinarily based on relatively modest preclinical data. This report defines the battery of preclinical tests important for assessing safety under an Investigational New Drug application (IND) and outlines a basis for extrapolating starting doses of investigational anticancer drugs in phase I clinical trials from animal toxicity studies. Types of preclinical studies for the support of marketing of a new anticancer drug are also discussed. This report addresses differences and similarities in the preclinical development of cytotoxic drugs (including photosensitizers and targeted delivery products), drugs used chronically (chemopreventive drugs, hormonal drugs, immunomodulators), and drugs intended to enhance the efficacy (MDR-reversing agents and radiation/chemotherapy sensitizers) or diminish the toxicity of currently used anticancer therapies. Factors to consider in the design of preclinical studies of combination therapies, alternative therapies, and adjuvant therapies in the treatment of cancer, and to support changes in clinical formulations or route of administration, are also discussed.

MPP+ (1-methyl-4-phenylpyridine) is a neurotoxin to dopamine-, norepinephrine- and serotonin-containing neurons.

1-Methyl-4-phenylpyridine (MPP+) is an oxidative metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP). MPP+ produced local cell death when injected directly into substantia nigra compacta, locus coeruleus, or dorsal and median raphe nuclei of rats. Corresponding significant decreases in dopamine, serotonin and norepinephrine levels were observed in the terminal areas. These observations indicate that MPP+ is a non-selective neurotoxin which causes lesions not only in dopaminergic neurons but also in noradrenergic and serotonergic systems following intracranial administration. Selective lesioning of these monoaminergic systems could only be achieved by a stereotaxic injection of MPP+ into specific brain regions containing monoamine neurons.