Utilizing plasma drug levels and genetic testing to achieve optimal treatment response in a patient with treatment-resistant schizoaffective disorder.

We report the case of a Chinese male with schizoaffective disorder, an active smoker and a nonresponder to clozapine (600 mg daily). Therapeutic clozapine monitoring was analyzed, revealing a low concentration-dose ratio. A pharmacogenetic test showed that the patient had the CYP1A2*1F/*1F genotype, indicating an ultra-rapid clozapine metabolizer. In combination with fluvoxamine, a CYP1A2 enzyme inhibitor, clozapine plasma concentrations approached the reference range and achieved clinical improvement. This case demonstrates how pharmacogenetics can help understand the value of therapeutic drug monitoring to enhance the treatment of refractory schizoaffective disorder.

Integration of Deep Learning and Sequential Metabolism to Rapidly Screen Dipeptidyl Peptidase (DPP)-IV Inhibitors from Gardenia jasminoides Ellis.

Traditional Chinese medicine (TCM) possesses unique advantages in the management of blood glucose and lipids. However, there is still a significant gap in the exploration of its pharmacologically active components. Integrated strategies encompassing deep-learning prediction models and active validation based on absorbable ingredients can greatly improve the identification rate and screening efficiency in TCM. In this study, the affinity prediction of 11,549 compounds from the traditional Chinese medicine system's pharmacology database (TCMSP) with dipeptidyl peptidase-IV (DPP-IV) based on a deep-learning model was firstly conducted. With the results, Gardenia jasminoides Ellis (GJE), a food medicine with homologous properties, was selected as a model drug. The absorbed components of GJE were subsequently identified through in vivo intestinal perfusion and oral administration. As a result, a total of 38 prototypical absorbed components of GJE were identified. These components were analyzed to determine their absorption patterns after intestinal, hepatic, and systemic metabolism. Virtual docking and DPP-IV enzyme activity experiments were further conducted to validate the inhibitory effects and potential binding sites of the common constituents of deep learning and sequential metabolism. The results showed a significant DPP-IV inhibitory activity (IC50 53 ± 0.63 µg/mL) of the iridoid glycosides' potent fractions, which is a novel finding. Genipin 1-gentiobioside was screened as a promising new DPP-IV inhibitor in GJE. These findings highlight the potential of this innovative approach for the rapid screening of active ingredients in TCM and provide insights into the molecular mechanisms underlying the anti-diabetic activity of GJE.

[Study on drug-target binding kinetics profiles of flavonoids in Chrysanthemum morifolium and xanthine oxidase].

Based on the target occupancy mathematical model, the binding kinetic process of potential active ingredients of lowering uric acid in Chrysanthemum morifolium with xanthine oxidase(XOD) was evaluated. The potential active ingredients of lowering uric acid in Ch. morifolium were screened by UPLC-Q-Exactivems MS technology, reference substance identification and in vitro enzymatic kinetics experiments. The binding kinetic parameters of xanthine oxidase and potential inhibitor in Ch. morifolium were determined by surface plasma resonance(SPR). The verified mathematical model of the XOD target occupancy evaluated the kinetic binding process of inhibitors and xanthine oxidase in vivo. According to UPLC-Q-Exactive MS and reference substance identification, 39 potential uric acid-lowering active ingredients in Ch. morifolium extracts were identified and the inhibitory activities of 23 compounds were determined. Three potential xanthine oxidase inhibitors were screened, namely genistein, luteolin, and apigenin. whose IC_(50 )were 1.23, 1.47 and 1.59 µmol·L~(-1), respectively. And the binding rate constants(K_(on)) were 1.26×10~6, 5.23×10~5 and 6.36×10~5 mol·L~(-1)·s~(-1), respectively. The dissociation rate constants(K_(off)) were 10.93×10~(-2), 1.59×10~(-2), and 5.3×10~(-2 )s~(-1), respectively. After evaluation by different administration methods, the three selected compounds can perform rapid and sustained inhibition of xanthine oxidase in vivo under combined administration. This study comprehensively evaluated the target occupancy process of three effective components in different ways of administration in vivo by UPLC-MS, concentration-response method, SPR technology and xanthine oxidase target occupancy model, which would provide a new research idea and method for screening active ingredients in traditional Chinese medicine.

Use of electroconvulsive therapy in older Chinese psychiatric patients.

OBJECTIVE: Little is known about the use of electroconvulsive therapy (ECT) in older Chinese psychiatric patients. This study examined the frequency of ECT and the demographic and clinical correlates in older psychiatric patients hospitalized in a large psychiatric institution in Beijing, China. METHODS: This was a retrospective chart review of 2339 inpatients aged 60 years and older treated over a period of 8 years (2007-2013) in a university-affiliated psychiatric institution in Beijing. Sociodemographic and clinical data were collected from the electronic chart management system for discharged patients. RESULTS: The rate of ECT use was 28.1% in the whole sample; 37.9% in those with bipolar disorders, 43.6% in major depression, 21.2% in schizophrenia, and 10.7% in other diagnoses. ECT ("ECT group") was associated with 60-65-year age group, high risk for suicide and low risk for falls at the time of admission, use of mood stabilizers and antidepressants, lack of health insurance, and having major medical conditions and diagnosis of major depression. The above significant correlates explained 24.9% of the variance of ECT use (p < 0.001). CONCLUSIONS: In a major psychiatric hospital in China, the use of ECT was common among older patients. ECT use in older patients treated in other clinical settings warrants further investigations.

Electroconvulsive therapy and its association with demographic and clinical characteristics in Chinese psychiatric patients.

PURPOSE: Little is known about the frequency of electroconvulsive therapy (ECT) use in China. This study examined the frequency of ECT and its relationship with demographic and clinical characteristics in a large psychiatric institution in China. METHODS: This was a retrospective chart review of all the 19,982 inpatients aged 18 to 59 years treated during the period of 8 years (2007-2013) in a tertiary psychiatric institution in Beijing. Sociodemographic and clinical data were collected from the electronic chart management system for discharged patients. RESULTS: The frequency of ECT use was 57.7% in the whole sample, 68.4% in bipolar disorders, 66.3% in major depression, 55.2% in schizophrenia, and 28.6% in other psychiatric disorders. Patients who received ECT (ECT group) had shorter length of hospitalization compared with the non-ECT group. In multiple logistic regression analysis, ECT use was independently associated with age younger than 30 years; higher risk for suicide and aggression at time of admission; mood disorders; lower risk for falls; more treatment with antipsychotics, mood stabilizers, and antidepressants; less health insurance coverage and major medical conditions; as well as non-local residency status. Compared with 2007 (35.5%), ECT use significantly increased in the period of 2008 (49.1%) to 2013 (61.9%). All these significant correlates combined explained 20% of the variance of ECT use (P < 0.001). CONCLUSIONS: In a major psychiatric center in China, the use of ECT was much more common than the figures reported from most countries around the world. Reasons for this difference and variances in outcomes between settings with higher and lower ECT use should be studied.

The Role of Traditional Chinese Medicine in the Management of Cervical Cancer.

Globally, cervical cancer poses a substantial public health challenge, with low and middle-income countries bearing the highest burden [Rajkhowa, P., D.S. Patil, S.M. Dsouza, P. Narayanan and H. Brand. Evidence on factors influencing HPV vaccine implementation in South Asia: a scoping review. Glob. Public Health 18: 2288269, 2023]. The incidence rate ranks second highest among female malignant tumors in China, following only breast cancer. The prognosis of advanced cervical cancer is extremely poor, with a 5-year progression-free survival (PFS) rate of only 15%, and the treatment of advanced recurrent or metastatic cervical cancer remains a huge challenge. An increasing amount of evidence suggests that traditional Chinese medicine (TCM) can significantly enhance sensitivity to chemotherapeutic drugs, strengthen antitumor effects, and notably improve adverse reactions associated with cancer such as fatigue and bone marrow suppression. In recent years, the therapeutic effects and mechanisms of Chinese herbal medicines, such as the Guizhi-Fuling-decoction, the compound Yangshe granule, Huangqi, and Ginseng, herbal monomers (e.g., Ginsenoside Rh2, Tanshinone IIA, and Tetrandrine), and the related extracts and compound formulations, have received extensive attention for the treatment of cervical cancer. This paper reviews the research progress of TCM in cervical cancer. In addition, we reported a case of an advanced cervical cancer patient with multiple abdominal and pelvic metastasis who initially received chemotherapy, was then treated with TCM alone, and subsequently survived for 22 years. The model of whole-process management with TCM can enable more cancer patients to obtain longer survival periods.

Finite element model reveals the involvement of cartilage endplate in quasi-static biomechanics of intervertebral disc degeneration.

Background and objective: The intrinsic link between the compositional and structural attributes and the biomechanical functionality is evident in intervertebral discs. However, it remains unclear from a biomechanical perspective whether cartilage endplate (CEP) degeneration exacerbates intervertebral disc degeneration. Methods: This study developed and quantitatively validated four biphasic swelling-based finite element models. We then applied four quasi-static tests and simulated daily loading scenarios to examine the effects of CEP degradation. Results: Under free-swelling conditions, short-term responses were prevalent, with CEP performance changes not significantly impacting response proportionality. The creep test results showed the more than 50 % of the strain was attributed to long-term responses. Stress-relaxation testing indicated that all responses increased with disc degeneration, yet CEP degeneration's impact was minimal. Daily load analyses revealed that disc degeneration significantly reduces nucleus pulposus pressure and disc height, whereas CEP degeneration marginally increases nucleus pressure and slightly decreases disc height. Conclusions: Glycosaminoglycan content and CEP permeability are critical to the fluid-dependent viscoelastic response of intervertebral discs. Our findings suggest that CEP contributes to disc degeneration under daily loading conditions.

Sociodemographic, clinical and treatment characteristics of current rapid-cycling bipolar disorder: a multicenter Chinese study.

BACKGROUND: Rapid cycling bipolar disorder (RCBD), characterized by four or more episodes per year, is a complex subtype of bipolar disorder (BD) with poorly understood characteristics. METHOD: This multicenter, observational, longitudinal cohort study enrolled 520 BD patients across seven psychiatric institutions in China from January 2013 to January 2014. Participants were divided into RCBD and non-RCBD (NRCBD) groups based on the frequency of mood episodes in the preceding year. Data collection utilized a standardized form, supplemented by a medical record review, focusing on sociodemographic, clinical, and treatment characteristics. Statistical analysis involved independent samples t-tests, Kruskal-Wallis H tests, Chi-square or Fisher's exact tests, with Bonferroni correction applied to account for multiple comparisons, and multivariable logistic regression to identify characteristics associated with RCBD. RESULTS: Among the BD cohort, 9.4% were identified as current RCBD. Compared to NRCBD, RCBD patients had a shorter duration from the first psychiatric consultation to the diagnosis of BD, a reduced duration of their longest period of euthymia, a lower proportion of lifetime hospitalization history due to BD, and less use of electroconvulsive therapy (ECT) within the last 12 months. Additionally, they presented higher baseline scores on the Mood Disorder Questionnaire (MDQ) and the Brief 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). However, after applying the Bonferroni correction, these differences were not statistically significant. Multivariable logistic regression analysis identified three factors that were independently associated with RCBD: time from first psychiatric consultation to BD diagnosis (Odds Ratio [OR] = 0.512, P = 0.0416), lifetime hospitalization history due to BD (OR = 0.516, P = 0.0476), and ECT treatment within the past 12 months (OR = 0.293, P = 0.0472). CONCLUSION: This study revealed that the duration from first psychiatric consultation to BD diagnosis, lifetime hospitalization history due to BD, and ECT treatment in the past year were associated with RCBD. Recognizing these factors could contribute to enhance the early identification and clinical outcomes of RCBD. Trial Registration Number Registry ClinicalTrials.gov NCT01770704. Date of Registration: First posted on January 18, 2013.

Immune-inflammatory responses and pulmonary embolism in Catatonia: A report of two cases.

Venous thromboembolism (VTE) comprises pulmonary embolism (PE) and deep vein thrombosis (DVT). PE, as the most severe manifestation of VTE, can cause increased mortality in patients with mental disorders. Here we describe two cases of young male patients with catatonia who developed PE and DVT during their hospital stay. We also discuss the possible pathogenesis, with a focus on immune and inflammatory mechanisms.

Rapid screening and in vivo target occupancy quantitative evaluation of xanthine oxidase inhibitors based on drug-target binding kinetics research strategy: A case study of Chrysanthemum morifolium Ramat.

Chrysanthemum morifolium Ramat. is a kind of food and drug dual-use traditional Chinese medicine possessing multiple pharmacological and biochemical benefits. In our study, a rapid and high-throughput method based on Surface plasmon resonance (SPR) biosensor technology was developed and verified for screening potential xanthine oxidase (XOD) inhibitors exemplarily in the Chrysanthemum morifolium Ramat. Coupled with ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS), 14 XOD-binders were identified. In the SPR-based biosensor and molecular docking analysis, most compounds exhibited a strong affinity and binding kinetic property (association rate constant, Kon and dissociation rate constant, Koff) for XOD and could be regarded as potential inhibitors. More importantly, to further accurately assess target occupancy of candidate compounds in vivo, a mathematical model was established and verified involving three crucial intrinsic kinetic processes (Pharmacokinetics, Binding kinetic and Target kinetic). Overall, the proposed screening and assessment strategy could be proved an effective theoretical basis for further pharmacodynamic evaluation.

The brain-derived neurotrophic-factor (BDNF) val66met polymorphism is associated with geriatric depression: a meta-analysis.

Depression has been associated with reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. Genetic association studies of the BDNF Val66Met polymorphism (rs6265) in geriatric depression have produced inconsistent results. A meta-analysis of studies was conducted to compare the frequency of the BDNF Val66Met variant between cases with geriatric depression and age-matched controls. A total of five studies involving 523 cases with geriatric depression and 1,220 psychiatrically healthy controls was included. Met allele carriers had an increased risk for geriatric depression when compared to Val/Val homozygotes (P = 0.004, OR = 1.48, 95% CI = 1.13-1.93). Our findings suggest the BDNF Met allele may confer increased risk for depression as individual age.

Identification, Screening, and Comprehensive Evaluation of Novel DPP-IV Inhibitory Peptides from the Tilapia Skin Gelatin Hydrolysate Produced Using Ginger Protease.

PURPOSE: Inhibition of dipeptidyl peptidase-IV (DPP-IV) is an effective therapy for treating type II diabetes (T2D) that has been widely applied in clinical practice. We aimed to evaluate the DPP-IV inhibitory properties of ginger protease hydrolysate (GPH) and propose a comprehensive approach to screen and evaluate DPP-IV inhibitors. METHODS: We evaluated the in vitro inhibitory properties of fish skin gelatin hydrolysates produced by five proteases, namely, neutral protease, alkaline protease, bromelain, papain, and ginger protease, toward DPP-IV. We screened the most potent DPP-IV inhibitory peptide (DIP) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) coupled with in silico analysis. Next, surface plasmon resonance (SPR) technology was innovatively introduced to explore the interactions between DPP-IV and DIP, as well as the IC50. Furthermore, we performed oral administration of DIP in rats to study its in vivo absorption. RESULTS: GPH displayed the highest degree of hydrolysis (20.37%) and DPP-IV inhibitory activity (65.18%). A total of 292 peptides from the GPH were identified using LC-MS/MS combined with de novo sequencing. Gly-Pro-Hyp-Gly-Pro-Pro-Gly-Pro-Gly-Pro (GPXGPPGPGP) was identified as the most potent DPP-IV inhibitory peptide after in silico screening (Peptide Ranker and molecular docking). Then, the in vitro study revealed that GPXGPPGPGP had a high inhibitory effect on DPP-IV (IC50: 1012.3 ± 23.3 µM) and exhibited fast kinetics with rapid binding and dissociation with DPP-IV. In vivo analysis indicated that GPXGPPGPGP was not absorbed intact but partially, in the form of dipeptides and tripeptides. CONCLUSION: Overall, the results suggested that GPH would be a natural functional food for treating T2D and provided new ideas for searching and evaluating potential antidiabetic compounds. The obtained GPXGPPGPGP can be structurally optimized for in-depth evaluation in animal and cellular experiments.

Accurate quantitative determination of affinity and binding kinetics for tight binding inhibition of xanthine oxidase.

The accurate quantitative determination of affinity and binding kinetics (BK) for tight binding inhibition is extraordinary important from both the continuous optimization of compounds, particularly in developing structure-activity relationships (SAR), and the prediction of in vivo target occupancy (TO). Due to the unique properties for tight binding inhibition that the inhibitors are characterized by the ultrahigh-affinity, relatively fast association to the target enzyme combined with extremely slow dissociation of the inhibitor-enzyme binary complex, the classical steady state equilibrium methods are no longer valid. Here, we made several recommendations of how to design the optimal experiments and apply special mathematical calculation approaches to quantitatively evaluate the accurate affinity and BK as the examples of two tight binding inhibitors against the xanthine oxidase (XO), as well as compared the differences in the results calculated from the different data analytical methods and analyzed the influence of these differences on the XO engagement in human. Analysis of the results displayed that the accurate apparent dissociation constant (Ki*,app) was 0.2 ± 0.06 nM for topiroxotstat and was 0.45 ± 0.2 nM for febuxostat; that on-rate (kon) was (4.3 ± 1.1) × 106 M-1s-1 for topiroxotstat and was(133.3 ± 3.5) × 106 M-1s-1 for febuxostat, and off-rate (koff) was (1.0±0.2) × 10-5 s-1 for topiroxotstat and was ≤ 0.16 × 10-5 s-1for febuxostat. Moreover, there were significant differences in the Ki*,app and koff values estimated using the appropriate specialized methods for tight binding inhibition versus classical steady state equilibrium methods, with the substantial differences of 14-fold and 32-fold reduction for topiroxostat, respectively, and of 9.6-fold and ≥ 213-fold reduction for febuxostat, while the kon values remain the moderate differences for the two inhibitors. The obvious greater AUC of XO engagement time courses and longer durations of above 70% engagement by the appropriate specialized methods for tight binding inhibition were observed that the results display the differences of 70.1% and 88%, respectively for topiroxostat and of 38.1% and 35.0%, respectively for febuxostat in human liver cell than by classical steady state equilibrium methods. Again, our studies provide several valuable recommendations of the optimal experiment protocols and appropriate analytical approaches for accurately quantitatively assessing the affinity and BK parameters as well as demonstrate the ability of our recommended methods to generate reliable data for tight binding inhibitors against XO.

Utilizing the Combination of Binding Kinetics and Micro-Pharmacokinetics Link in Vitro α-Glucosidase Inhibition to in Vivo Target Occupancy.

Many compounds with good inhibitory activity (i.e., high affinity) within in vitro experiments failed in vivo studies due to a lack of efficacy from limited target occupancy (TO) in the drug discovery process. Recently, it was found that rate constants of the formation and dissociation of the binary drug-target complex, rather than affinity, often govern in vivo efficacy. Therefore, the binding kinetics (BK) properties of compound-target interaction are emerging as a pivotal parameter. However, it is obvious that BK rate constants of the compound against target would not be directly linked to the in vivo TO unless the compound concentration in the target vicinity at any time point (TPK) can be evaluated. Here, we developed a novel simulation model to quantitate the dynamic change of target engagement over time in rat with a combined use of BK and TPK features of Epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) on the basis of α-glucosidase (AGH). Analysis of the results displayed that the percent of maximum AGH occupancies by the ECG were varied significantly from 48.9 to 95.3% and by the EGCG slightly from 96 to 99.8%; that the time course of above 70% engagement by ECG spanned a range from 0 to 0.64 h and by EGCG a range of 1.5 to 8.9 h in four different intestinal segments of the rat. It was clearly analyzed how each parameter in the simulation model effected on the in vivo the AGH engagement by ECG and EGCG. Our results provide a novel approach for assessing the potential inhibitory activity of the compounds against AGH.

Schizophrenia Patient Shows a Rare Interleukin 15 Receptor alpha Variant Disrupting Signal Transduction.

BACKGROUND: Schizophrenia is a complex and debilitating mental disorder with strong heritability. Its pathogenesis involves immune dysregulation. Interleukin 15 and interleukin 15 receptor alpha(IL-15Rα) are classical immune molecules. They also help maintain normal brain function, leading to our hypothesis that IL-15Rα gene(IL- 15RA) variants contribute to the pathogenesis of schizophrenia. OBJECTIVE: We determine whether the genetic variants of IL-15RA are associated with the development and progression of schizophrenia and whether IL-15RA single nucleotide polymorphism(SNP) plays a key role in downstream signaling transduction. METHODS AND RESULTS: We sequenced IL-15RA exon from 132 Chinese schizophrenic patients and identified a rare variant(rs528238821) in a patient diagnosed with catatonic schizophrenia and ankylosing spondylitis(AS). We overexpressed this missense variant in cells driven by pBI-CMV vector. The cells showed attenuated STAT3 phosphorylation in response to interleukin15. CONCLUSION: IL-15RA mutation is rare in schizophrenic patients but interfered with IL- 15Rα intracellular signal transduction. Given the similarity of symptoms of catatonic schizophrenia and the known phenotype of IL-15Rα knockout mice, gene variation might offer diagnostic value for sub-types of schizophrenia.

[Thinking on TCM literature evaluation methods and techniques based on mass information].

The necessity and feasibility of TCM literature evaluation based on mass information of TCM literature was discussed in this paper. Beginning with the description on current situation of mass TCM literature information research, the authors offered a tentative plan for evaluating scientific and technologic TCM literature, its method and technique, and systematically analyzed the key issues, such as the subjects selection, documents screening and sorting, literature analysis, and development of software analysis platform, then, the methodology and the technology for constituting the mass TCM literature information based evaluation system was systemically clarified.

Water-fat separation with parallel imaging based on BLADE.

Uniform suppression of fat signal is desired in clinical applications. Based on phase differences introduced by different chemical shift frequencies, Dixon method and its variations are used as alternatives of fat saturation methods, which are sensitive to B0 inhomogeneities. Iterative Decomposition of water and fat with Echo Asymmetry and Least squares estimation (IDEAL) separates water and fat images with flexible echo shifting. Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction (PROPELLER, alternatively termed as BLADE), in conjunction with IDEAL, yields Turboprop IDEAL (TP-IDEAL) and allows for decomposition of water and fat signal with motion correction. However, the flexibility of its parameter setting is limited, and the related phase correction is complicated. To address these problems, a novel method, BLADE-Dixon, is proposed in this study. This method used the same polarity readout gradients (fly-back gradients) to acquire in-phase and opposed-phases images, which led to less complicated phase correction and more flexible parameter setting compared to TP-IDEAL. Parallel imaging and undersampling were integrated to reduce scan time. Phantom, orbit, neck and knee images were acquired with BLADE-Dixon. Water-fat separation results were compared to those measured with conventional turbo spin echo (TSE) Dixon and TSE with fat saturation, respectively, to demonstrate the performance of BLADE-Dixon.

Enhanced antidepressant-like effects of electroacupuncture combined with citalopram in a rat model of depression.

Currently, antidepressants are the dominative treatment for depression, but they have limitations in efficacy and may even produce troublesome side effects. Electroacupuncture (EA) has been reported to have therapeutic benefits in the treatment of depressive disorders. The present study was conducted to determine whether EA could enhance the antidepressant efficacy of a low dose of citalopram (an SSRI antidepressant) in the chronic unpredictable stress-induced depression model rats. Here, we show that a combined treatment with 2 Hz EA and 5 mg/kg citalopram for three weeks induces a significant improvement in depressive-like symptoms as detected by sucrose preference test, open field test, and forced swimming test, whereas these effects were not observed with either of the treatments alone. Further investigations revealed that 2 Hz EA plus 5 mg/kg citalopram produced a remarkably increased expression of BDNF and its receptor TrkB in the hippocampus compared with those measured in the vehicle group. Our findings suggest that EA combined with a low dose of citalopram could produce greater therapeutic effects, thereby, predictive of a reduction in drug side effects.

The antioxidative effect of electro-acupuncture in a mouse model of Parkinson's disease.

Accumulating evidence indicates that oxidative stress plays a critical role in Parkinson's disease (PD). Our previous work has shown that 100 Hz electro-acupuncture (EA) stimulation at ZUSANLI (ST36) and SANYINJIAO (SP6) protects neurons in the substantia nigra pars compacta from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity in male C57BL/6 mice, a model of PD. In the present study we administered 100 Hz EA stimulation at the two acupoints to MPTP-lesioned mice for 12 sessions starting from the day prior to the first MPTP injection. We found that in the striatum of MPTP treated mice 100 Hz EA stimulation effectively inhibited the production of hydrogen peroxide and malonaldehyde, and increased glutathione concentration and total superoxide dismutase activity through biochemical methods. However, it decreased glutathione peroxidase activity via biochemical analysis and did not affect the level of 1-methyl-4-phenylpyridinium in the striatum revealed by high performance liquid chromatography with ultraviolet detection. These data suggest that 100 Hz EA stimulation at ST36 and SP6 has antioxidative effects in the MPTP model of PD. This data, along with our previous work, indicates that 100 Hz EA stimulation at ST36 and SP6 protects the nigrostriatal system by multiple mechanisms including antioxidation and antiapoptosis, and suggests that EA stimulation is a promising therapy for treating PD.

Electro-acupuncture stimulation improves motor disorders in Parkinsonian rats.

Electro-acupuncture (EA) is believed to be effective for alleviating motor symptoms in patients with Parkinson's disease. In a rat hemiparkinsonian model induced by unilateral transection of the medial forebrain bundle (MFB), the effects of EA stimulation were investigated. EA stimulation at a high frequency (100 Hz) significantly reduced apomorphine-induced rotational behavior. Tyrosine hydroxylase immunohistochemical staining revealed that EA at 100 Hz protected axotomized dopaminergic neurons from degeneration in the substantia nigra (SN). Moreover, high frequency EA reversed the axotomy-induced decrease in substance P content and increase in glutamate decarboxylase-67 (GAD 67) mRNA level in the midbrain; however, it did not affect the axotomy-induced increase in enkephalin content in the globus pallidus. These results suggest that the effects of high frequency EA on motor symptoms of Parkinsonian rats may involve restoration of the homeostasis of dopaminergic transmission in the basal ganglia circuit.