Levodopa improved different motor symptoms in patients with Parkinson's disease by reducing the functional connectivity of specific thalamic subregions.

BACKGROUND: The thalamus is an important relay station for the motor circuit of human. Levodopa can reverse the clinical manifestations by modulating the function of motor circuits, but its detailed mechanisms are still not fully understood. We aimed to explore (1) the mechanism by which levodopa modulates the functional connectivity (FC) in the subregions of the thalamus; (2) the relationship between the changed FC and the improvement of motor symptoms in Parkinson's disease (PD) patients. METHODS: Resting-state functional MRI was used to scan 36 PD patients and 37 healthy controls. The FC between the subregions in the thalamus and the whole brain was measured and compared under different medication states of PD patients. The correlation between the improvement of motor symptoms and changes in FC in the thalamus subregions was examined. RESULTS: The PD on state exhibited decreased FC between the right pre-motor thalamus and the right postcentral gyrus, as well as the right lateral pre-frontal thalamus and the right postcentral gyrus. These decreases were positively correlated with the improvement of resting tremor. The PD on state also exhibited decreased FC between the left lateral pre-frontal thalamus and right paracentral lobule, which was positively correlated with the improvement of bradykinesia. CONCLUSIONS: This study demonstrates that levodopa treats PD by decreasing the FC between the thalamus subregions and pre/post-central cortex. Our results provide a basis for further exploration of the functional activity of thalamic subregions and offer new insights into the precision treatment in PD patients.

Effect of Zishen pingchan granules combined with pramipexole on serum BDNF, IL-1ß, IL-6, CRP, TNF-α levels in depressed patients with Parkinson's disease: Results of a randomized, double-blind, controlled study.

INTRODUCTION: Depression is a common comorbidity in Parkinson's Disease (PD) and treatment of depression can significantly support PD management. Zishen pingchan granules (ZPG), a traditional Chinese herbal formula, may help ameliorate depressive symptoms in PD patients. However, the molecular mechanisms underlying the effects of ZPG remain unclear. This study aimed to investigate the impact of ZPG on serum levels of brain-derived neurotrophic factor (BDNF), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) in PD patients with depression. METHODS: Eighty PD patients treated with pramipexole but still experiencing mild to moderate depression symptoms were randomly allocated to a group receiving 12-week ZPG treatment (n = 40) or placebo (n = 40). The Hamilton Depression Scale 17 items (HAM-D-17) was utilized to evaluate changes in depressive symptoms from baseline over 12 weeks, while the Unified Parkinson's Disease Rating Scales (UPDRS) part 3 was employed to assess changes in motor symptoms over the same duration. Serum levels of BDNF, IL-1ß, IL-6, CRP, and TNF-α were measured at baseline and post-treatment. RESULTS: Seventy-one participants completed the study. Following treatment, both groups showed significantly reduced HAMD scores. The placebo group demonstrated a decrease in BDNF levels, while the ZPG group showed an increase in IL-6 levels post-treatment. In the examination of the group-time interaction, the ZPG group exhibited a greater decrease in HAMD scores and increase in IL-6 levels compared to the placebo group. Conversely, the placebo group showed a greater decrease in BDNF levels compared to the ZPG group. However, no significant group differences were observed in UPDRS part 3 change scores or serum levels of IL-1ß, CRP, or TNF-α change from baseline. CONCLUSION: ZPG may potentially ameliorate depressive symptoms in PD patients, with the potential mechanism involving mitigation of reductions in serum BDNF level and an increase in IL-6 level.

Network pharmacology and molecular docking to explore the mechanism of Sheng Xue Bao mixture against iron deficiency anemia.

Based on network pharmacology and molecular docking, we investigated the mechanism of action of Sheng Xue Bao mixture (SXBM) in treating iron deficiency anemia (IDA). We screened the HERB and traditional Chinese medicine systems pharmacology database and analysis platform databases to identify the active ingredients and targets of SXBM. The targets associated with "iron deficiency anemia" were collected from GeneCards, TTD, and OMIM databases. A component-target interaction network was constructed using Cytoscape 3.8.2. The protein-protein interaction network of candidate targets was generated using the STRING database and visualized with Cytoscape 3.8.2 software. Core modules obtained from clustering analysis were subjected to Gene Ontology and Kyoto encyclopedia of genes and genomes enrichment analysis. Finally, molecular docking validation of key targets and active components was performed using Autodock Vina software. A total of 174 active components and 111 genes were identified as potential active components and targets for IDA treatment, including quercetin, kaempferol, luteolin, beta-sitosterol, and other flavonoids as main active components. Gene Ontology enrichment analysis show that interleaved genes are enriched in 2328 biological processes, 71 cellular component expression processes, and 157 molecular function processes. Kyoto encyclopedia of genes and genomes analysis mainly envolved Prostate cancer, Hepatitis B, Kaposi sarcoma-associated herpesvirus infection, Endocrine resistance, Lipid and atherosclerosis, Central carbon metabolism in cancer, Human cytomegalovirus infection and HIF-1 signaling pathway. STAT3, SRC, PIK3R1, and GRB2 were selected as core targets. The molecular docking results demonstrated strong interactions between key components and their respective target proteins. Network pharmacological analysis suggested that SXBM could treat IDA by regulating various biological processes and related signaling pathways. It laid the foundation for further elucidating the molecular mechanism of SXBM treatment of IDA.

[Clinical observation of acupotomy combined with warm needling for cervical spondylotic radiculopathy of qi and blood stagnation syndrome].

OBJECTIVE: To observe the clinical effect of acupotomy combined with warm needling on cervical spondylotic radiculopathy (CSR) of qi and blood stagnation syndrome. METHODS: A total of 90 CSR patients were randomly divided into an acupotomy group, a warm needling group and a combined treatment group, with 30 cases in each group. The patients in the acupotomy group were treated with acupotomy, once every 7 days, consecutively for 3 times. The patients in the warm needling group received warm needling, once daily, at the interval of 2 days after consecutive treatments for 5 days, 7 days as one session of treatment and 3 consecutive sessions were required. The patients in the combined treatment group were treated with acupotomy and warm needling, and the methods and the treatment session were same as the the previous two groups. Before and after the treatment, the pain rating index (PRI) of McGill pain questionnaire (MPQ) and the 20-point scale of CSR developed by Yasuhisa Tanaka (CSR20) were adopted in the assessment. The changes of clinical symptoms and functions of patients were observed and the clinical efficacy was assessed in each group. RESULTS: After the treatment, the PRI score was decreased (P<0.05) and the CSR20 score was increased (P<0.05) in the 3 treatment groups when compared with those before the treatment. After the treatment, compared with the acupotomy group and the warm needling group, the PRI score was decreased (P<0.05) and the CSR20 score was increased (P<0.05) in the combined treatment group. The total effective rate was 83.3% (25/30) in the acupotomy group, 76.7% (23/30) in the warm needling group and 93.3% (28/30) in the combined treatment group. The total effective rate in the combined treatment group was higher than those in the acupotomy group and the warm needling group (P<0.05). CONCLUSION: The combined treatment with acupotomy and warm needling may obviously improve the clinical symptoms and physical signs, e.g. pain and numbness in the patients with CSR of qi and blood stagnation syndrome. Its efficacy is remarkably higher than that of the simple application of acupotomy or warm needling.

Zishen pingchan granules combined with pramipexole in the improvement of depressive symptoms in Parkinson's disease: a prospective, multicenter, randomized, double-blind, controlled clinical study.

BACKGROUND AND OBJECTIVE: Zishen Pingchan granule (ZPG), a traditional Chinese herbal recipe for treating Parkinson's disease (PD), is usually used as an add-on drug with some antiparkinsonian drugs in China. The objectives of this study were to evaluate the efficacy, safety, and tolerability of ZPG combined with pramipexole in the treatment of depression in PD (dPD). METHODS: A 12-week, multicenter, randomized, double-blind, and placebo-controlled study on ZPG was performed on a total of 200 patients who were treated with pramipexole but still had mild to moderate depressive symptoms. Patients were randomly divided into ZPG (n = 100) or placebo (n = 100). The primary effective result was the mean change from the baseline on the Hamilton Depression Scale 17 items (HAM-D-17) over 12 weeks and the clinical efficacy rate. Secondary endpoints were the mean change from the baseline in the Geriatric Depression Scale (GDS-15), Unified Parkinson's disease rating scale Part III (UPDRS III), Parkinson's quality of life scale (PDQ-8), and Parkinson's disease sleep scale (PDSS-2) over 12 weeks. RESULTS: After 12 weeks of treatment, ZPG significantly reduced the mean [95% confidence interval] HAMD score vs. placebo (- 1.43 scores [- 2.50, - 0.36]; p = 0.009). The clinical remission rate and responders of the ZPG group were higher than those of the placebo (46.1% vs. 31.0%; p = 0.041; 34.8% vs. 18.4%; p = 0.014). A significant improvement in the PDSS-2 score was also observed in the ZPG group compared with that in the placebo group (- 3.56 scores [- 5.77, - 1.35]; p = 0.002). A total of 7 patients (7.1%) in the ZPG group had mild adverse events (AEs) vs 9 patients (9%) in the placebo group. No severe AEs were observed in either group. The randomization and controlled clinical study revealed that ZPG was effective, safe, and well-tolerated. CONCLUSION: ZPG combined with pramipexole further reduced the depressive symptoms and improved the sleeping quality of PD patients. Trial registration The protocol was retrospectively registered at the Chinese Clinical Trial Registry, Unique identifier: ChiCTR1800019942, date of registration: December 9, 2018; http://www.chictr.org.cn/showproj.aspx?proj=30432.

[Effect of balance acupotomy combined with warm needling in treatment of cervical spondylosis of vertebral artery type].

OBJECTIVE: To observe the clinical efficacy of balance acupotomy combined with warm needling in treatment of cervical spondylopathy of vertebral artery type (CSA). METHODS: Ninety patients were randomly divided into a warm needling group, a balance acupotomy group and a combined treatment group, 30 cases in each one. In the warm needling group, warm needling was given, once daily, for 5 days consecutively, with the interval of 2 days every week, and the treatment was conducted for 3 weeks. In the combined treatment group, on the base of the treatment as the warm needling group, the balance acupotomy was exerted, for consecutive 3 weeks. In the balance acupotomy group, the balance acupotomy was adopted, once a week, for 3 weeks consecutively. Clinical efficacy, the mean blood flow velocity of left vertebral artery (LVA), right vertebral artery (RVA) and basilar artery (BA), the pulse index (PI) and the resistance index (RI) were observed in 3 groups separately. The score of vertigo symptom and function was compared before and after treatment in 3 groups. RESULTS: In comparison with before treatment, the score of evaluation scale for cervical vertigo (ESCV) and the mean blood flow velocity of LVA, RVA and BA were all increased (P<0.05). while PI and RI reduced (P<0.05) in each group after treatment. In comparison with those in the warm needling group and the balance acupotomy group, ESCV score and the mean blood flow velocity of LVA, RVA and BA were increased (P<0.05), while PI and RI decreased (P<0.05) in the combined treatment group after treatment. Compared with the balance acupotomy group, the mean blood flow velocity of LVA, RVA and BA was increased (P<0.05), and PI and RI reduced (P<0.05) in the warm needling group after treatment. The total effective rate was 73.3% (22/30) in the warm needling group, 70.0% (21/30) in the balance acupotomy group and 93.3% (28/30) in the combined treatment group respectively. The total effective rate in the combined treatment group was higher than that either in the warm needling group or in the balance acupotomy group (P<0.05). CONCLUSION: Balance acupotomy combined with warm needling may restore the mechanical equilibrium state of the neck, and effectively improve the change of vertebral-basilar artery blood flow and relieve vertigo symptoms in patient with of cervical spondylosis of vertebral artery type.

Effect of liuzijue qigong on patients with stable chronic obstructive pulmonary disease: A systematic review and meta-analysis.

BACKGROUNDS: Chronic obstructive pulmonary disease (COPD) is a common, preventable disease of airflow limitation that accounts for the third leading deaths of any disease process in the worldwide. Health benefits of liuzijue qigong (LQG) on patients with stable COPD has been assessed. This study was designed to perform a systemic review and meta-analysis of the effect of Liuzijue breathing exercise on patients with stable COPD. METHODS: Published articles from 1970 to December 2020 were conducted using electronic searches. Two independents reviewers conducted data extraction. The Cochrane risk of bias assessment tool was used to evaluate the quality of the included studies. RESULTS: A total of 16 eligible trials with 1039 patients with stable COPD were identified. Compared with control group, the pool meta-analysis of LQG showed a significant improvement in forced expiratory volume in one second (FEV1) (MD = -0.16, 95% CI [0.09, 0.23], P < .00001), FEV1% (MD = 9.71, 95% CI [8.44, 10.98], P < .00001), the ratio of forced expiratory volume to forced vital capacity in the first second (FEV1/FVC [%]) (MD = 4.81, 95% CI [2.12, 7.51], P = .0005), 6 minutes walking distance (6MWD) (MD = 21.89, 95% CI [14.67, 29.11], P < .00001), health-related quality of life (SMD = -0.84, 95% CI [-1.12,-0.55], P < .00001) and modified medical research council dyspnea scale (mMRC) (MD = -0.73, 95% CI [-0.96, -0.50], P < .00001). The observed effect was more pronounced for short term and medium-term duration interventions of study. It also showed improvements in the secondary outcome measures by LQG. CONCLUSIONS: In this systematic review and meta-analysis, LQG can improve lung ventilation function, exercise endurance and health-related quality of life of patients with stable COPD. ETHIC AND DISSEMINATION: This study is a systematic review and it does not involve harming to the rights of participants. Ethical approval will not be require for this study. The research results may be published in a peer-reviewed journals.

[Clinical effect of "Jin's three-needle" therapy and motor relearning regimen on the upper limb motor function in patients with ischemic stroke].

OBJECTIVE: To explore the clinical effect of "Jin's three-needle" therapy and motor relearning regime for the recovery of upper limb motor function in the patients with ischemic stroke. METHODS: A total of 60 patients with ischemic stroke were randomly divided into an experiment group (30 cases) and a control group (30 cases). In the control group, the routine rehabilitation regimen was adopted. In the experimental group, on the base of the treatment regimen as the control group, the "Jin's three-needle" therapy was supplemented. The neurological function deficit score was used to assess the neurological function. The modified Fugel-Meyer assessment for upper extremities (FMA) and motor assessment scale (MAS) were adopted to assess the upper limb motor function in patients. The modified Barthel Index (MBI) was used to evaluate the activity of daily living (ADL) in patients. RESULTS: After treatment, the neurological function deficit score, the upper limb motor function (FMA and MAS) and ADL (MBI) were all improved obviously as compared with those before treatment (P<0.05). In the experimental group, the reducing range of neurological function deficit score (difference value) was larger than that in the control group (P<0.05). The increases of FMA score (upper arm function), the total score of MAS, the score for hand movement in MAS and the score for advanced hand activities of MAS, as well as MBI score in the experimental group were significantly larger than those in the control group successively (P<0.05). CONCLUSION: "Jin's three-needle" therapy combined with exercise relearning regimen effectively reduces the degree of neurological deficit and improve the upper limb motor function and ADL in patients with ischemic stroke.

A novel ratiometric near-infrared fluorescent probe for monitoring cyanide in food samples.

Cyanide is a highly toxic anion. Nonetheless, many food plants could produce endogenous cyanide, which causes great danger to human health. Thus, monitoring cyanide in food samples is critically significant. Herein, we rationally developed the first ratiometric near-infrared fluorescent probe for sensing cyanide in food samples. The probe displayed noticeable fluorescence in near-infrared region. Moreover, upon treatment with cyanide, the probe exhibited highly selective and sensitive ratiometric fluorescence response, with limit of detection determined to be 0.075 µM and limit of quantification determined to be 0.25 µM. The ratios of fluorescent intensities at 519 and 688 nm (I519/I688) was linear with added cyanide concentrations from 0 to 80 µM. The relative standard deviations for repeatability and reproducibility varied from 0.55 to 8.94 and from 1.17 to 9.46, respectively. Significantly, probe Hy has been successfully applied for monitoring cyanide in various food samples, such as almonds, sprouting potatoes, and bamboo shoots.

Ameliorated light conditions increase the P uptake capability of soybean in a relay-strip intercropping system by altering root morphology and physiology in the areas with low solar radiation.

Belowground interspecific facilitation and complementarity contribute to the phosphorus (P) uptake advantages in the cereal-legume intercropping system. However, the root morphological and physiological plasticity and, subsequently, the P uptake capability response to light conditions in intercropping systems remain unclear. Soybean was grown under two levels of P application rates in sole and intercropping systems (maize/soybean relay strip intercropping) from 2016 to 2018 in Renshou, southwest of China. As a supplement to the field experiment, soybean was also grown in L-S (simulating the light conditions of sole cropping in the field: light first and then shading) and S-L (simulating the light conditions of intercropping in the field: shading first and then light) light conditions with two levels of P application in 2018 in a pot experiment. After maize harvest (approximately 3/4 of the soybean growth period), light capture in intercropping was higher than sole (ameliorated light conditions in intercropping system), which resulted in an advantage of P uptake in intercropped soybean. Both low P supply and more light capture increased the total root length and root APase activity. The genes GmEXPB2 (which is associated with root growth) and GmACP1 (which is associated with exudation of APase) were highly expressed in plants that captured more light under both P-sufficient and P-deficient conditions. Additionally, more light capture increased the production of lateral roots and the proportion of in the upper 15 cm soil layer roots at the reproductive stage in the field. Across the field and pot experiments, increased root morphological and physiological plasticity were associated with lower P concentrations in the leaves and greater allocation of photosynthates to roots as sucrose. It is suggested that ameliorated light conditions can regulate soybean root growth plasticity and, consequently, P uptake in maize/soybean relay strip intercropping systems, especially in the areas with low solar radiation.

Doubled Haploid Transgenic Wheat Lines by Microspore Transformation.

Microspores are preferred explant choice for genetic transformation, as their use shortens the duration of obtaining homozygous transformants. All established gene-delivery methods of particle bombardment, electroporation, and cocultivation with Agrobacterium tumefaciens were optimized on androgenic microspores or derived tissues. In the biolistic gene delivery method 35-40 days old haploid microspore embryoids were used for genetic transformation, whereas freshly isolated androgenic microspores were used for genetic transformation in the electroporation and Agrobacterium cocultivation-based methods. The genetic transformation methods of biolistic gene-delivery and electroporation gave rise to the chimeric plants, whereas the method involving cocultivation with Agrobacterium yielded homozygous transformants. These methods were tested on a large number of cultivars belonging to different market classes of wheat, and found to be fairly independent of the explant genotype. Other benefits of using microspores or derived tissues for transformation are: (1) a few explant donors are required to obtain desired transformants and (2) the time required for obtaining homozygous transformants is about 8 months in case of spring wheat genotypes and about a year in case of winter wheat genotypes.

Pharmacodynamic evaluation of the activities of six parenteral vancomycin products available in the United States.

A recent report found that generic parenteral vancomycin products may not have in vivo efficacies equivalent to those of the innovator in a neutropenic murine thigh infection model despite having similar in vitro microbiological activities and murine serum pharmacokinetics. We compared the in vitro and in vivo activities of six of the parenteral vancomycin products available in the United States. The in vitro assessments for the potencies of the vancomycin products included MIC/minimal bactericidal concentration (MBC) determinations, quantifying the impact of human and murine serum on the MIC values, and time-kill studies. Also, the potencies of the vancomycin products were quantified with a biological assay, and the human and mouse serum protein binding rates for the vancomycin products were measured. The in vivo studies included dose-ranging experiments with the 6 vancomycin products for three isolates of Staphylococcus aureus in a neutropenic mouse thigh infection model. The pharmacokinetics of the vancomycin products were assessed in infected mice by population pharmacokinetic modeling. No differences were seen across the vancomycin products with regard to any in vitro evaluation. Inhibitory sigmoid maximal bacterial kill (Emax) modeling of the relationship between vancomycin dosage and the killing of the bacteria in mice in vivo yielded similar Emax and EC50 (drug exposure driving one-half Emax) values for bacterial killing. Further, there were no differences in the pharmacokinetic clearances of the 6 vancomycin products from infected mice. There were no important pharmacodynamic differences in the in vitro or in vivo activities among the six vancomycin products evaluated.

Combination treatment with meropenem plus levofloxacin is synergistic against Pseudomonas aeruginosa infection in a murine model of pneumonia.

BACKGROUND: Meropenem plus levofloxacin treatment was shown to be a promising combination in our in vitro hollow fiber infection model. We strove to validate this finding in a murine Pseudomonas pneumonia model. METHODS: A dose-ranging study with meropenem and levofloxacin alone and in combination against Pseudomonas aeruginosa was performed in a granulocytopenic murine pneumonia model. Meropenem and levofloxacin were administered to partially humanize their pharmacokinetic profiles in mouse serum. Total and resistant bacterial populations were estimated after 24 hours of therapy. Pharmacokinetic profiling of both drugs was performed in plasma and epithelial lining fluid, using a population model. RESULTS: Meropenem and levofloxacin penetrations into epithelial lining fluid were 39.3% and 64.3%, respectively. Both monotherapies demonstrated good exposure responses. An innovative combination-therapy analytic approach demonstrated that the combination was statistically significantly synergistic (α = 2.475), as was shown in the hollow fiber infection model. Bacterial resistant to levofloxacin and meropenem was seen in the control arm. Levofloxacin monotherapy selected for resistance to itself. No resistant subpopulations were observed in any combination therapy arm. CONCLUSIONS: The combination of meropenem plus levofloxacin was synergistic, producing good bacterial kill and resistance suppression. Given the track record of safety of each agent, this combination may be worthy of clinical trial.

[Effects of potato/soybean intercropping on photosynthetic characteristics and yield of three soybean varieties].

The potato/soybean intercropping trials using three soybean varieties including Zhonghuang 30 (early-maturing variety) , Jidou 17 (mid maturing variety) and Qihuang 34 (late maturing variety) with the sole cropping potato as control were carried out to determine the dynamic changes of leaf area index (LAI) of soybean, accumulation of dry matter, photosynthetic characteristics, yield and yield components. The results showed that the LAI, dry matter accumulation, net photosynthesis (Pn), transpiration rate (Tr) and stomatal conduction (g(s)) of soybean in all intercropping systems were lower than in monoculture because of the influence of intensified lower light during earlier growing stage, and the duration from planting to flowering was extended. When the potato was harvested, the LAI, dry matter accumulation, Pn, Tr and g(s) of soybean in all intercropping systems increased, especially for mid-maturing and late-maturing varieties, which became much closer to those in the monoculture. Compared with sole cropping, the pods per plant, seeds per plant and seeds per pod in intercropping system significantly decreased by 22.0%, 36.0% and 17.6% for early-maturing soybean, 5.1%, 13.1% and 8.9% for mid-maturing soybean, 5.7%, 7.6% and 2.1% for late-maturing soybean, respectively. The yields of mid-maturing and late-maturing varieties in intercropping systems were higher than that of the early-maturing, which increased by 92.4% and 163.4%, with the land equivalent ratio (LER) of 1.81 and 1.84, respectively. This suggested that mid-maturing and late-maturing soybean varieties were suitable for intercropping with the potato to improve photosynthetic efficiency, dry matter accumulation and yield of intercropping soybean.

Generation of doubled haploid transgenic wheat lines by microspore transformation.

Microspores can be induced to develop homozygous doubled haploid plants in a single generation. In the present experiments androgenic microspores of wheat have been genetically transformed and developed into mature homozygous transgenic plants. Two different transformation techniques were investigated, one employing electroporation and the other co-cultivation with Agrobacterium tumefaciens. Different tissue culture and transfection conditions were tested on nine different wheat cultivars using four different constructs. A total of 19 fertile transformants in five genotypes from four market classes of common wheat were recovered by the two procedures. PCR followed by DNA sequencing of the products, Southern blot analyses and bio/histo-chemical and histological assays of the recombinant enzymes confirmed the presence of the transgenes in the T0 transformants and their stable inheritance in homozygous T1∶2 doubled haploid progenies. Several decisive factors determining the transformation and regeneration efficiency with the two procedures were determined: (i) pretreatment of immature spikes with CuSO4 solution (500 mg/L) at 4°C for 10 days; (ii) electroporation of plasmid DNA in enlarged microspores by a single pulse of ∼375 V; (iii) induction of microspores after transfection at 28°C in NPB-99 medium and regeneration at 26°C in MMS5 medium; (iv) co-cultivation with Agrobacterium AGL-1 cells for transfer of plasmid T-DNA into microspores at day 0 for <24 hours; and (v) elimination of AGL-1 cells after co-cultivation with timentin (200-400 mg/L).

Tracing the source of cooking oils with an integrated approach of using stable carbon isotope and fatty acid abundance.

We report a new approach to identify swill-cooked oils that are recycled from tainted food and livestock waste from commercial vegetable and animal oils by means of carbon isotope values and relative abundance of fatty acids. We test this method using 40 cooking oil samples of different types with known sources. We found significant differences in both total organic carbon isotope as well as compound-specific isotope values and fatty acid C(14)/C(18) ratios between commercial vegetable oils refined from C(3) plants (from -35.7 to -27.0‰ and from 0 to 0.15) and animal oils (from -28.3 to -14.3‰ and from 0.1 to 0.6). Tested swill-cooked oils, which were generally refined by mixing with animal waste illegally, fall into a narrow δ(13)C/fatty acid ratio distribution: from -25.9 to -24.1‰ and from 0.1 to 0.2. Our data demonstrate that the index of a cross-plotting between fatty acid δ(13)C values and C(14)/C(18) ratios can be used to distinguish clean commercial cooking oils from illegal swill-cooked oils.

[Parkinson's disease combined with depression treated with electroacupuncture and medication and its effect on serum BDNF].

OBJECTIVE: To verify the efficacy on Parkinson's disease combined with depression treated with electroacupuncture and medication and to explore the therapeutic mechanism. METHODS: Sixty cases of Parkinson's disease combined with depression were randomized into an acupuncture + medication group and a medication group, 30 cases in each one. The conventional therapeutic program of oral administration of madopar and fluoxetine was applied in both groups. In the acupuncture + medication group, on the basic treatment as the above, electroacupuncture was applied to Baihui (GV 20), Yintang (EX-HN 3), Sishencong (EX-HN 1), Taichong (LR 3) and Sanyinjiao (SP 6), etc. The level of the serum brain-derived neurotrophic factor (BDNF) and the score of Hamilton depression scale (HAMD) were observed and compared before treatment and after 3 months of treatment. The efficacy was assessed in two groups. RESULTS: The level of BDFN was improved significantly after treatment as compared with that before treatment in two groups (both P < 0.05) and the result in the acupuncture + medication group was superior to the medication group (P < 0.05). HAMD scores were reduced significantly after treatment as compared with those before treatment in two groups (both P < 0.05) and the result in the acupuncture + medication group was superior to the medication group (P < 0.05). The total effective rate was 90.0% (27/30) in the acupuncture + medication group, which was better than 83.3% (25/30) in the medication group (P < 0.05). CONCLUSION: The combined therapy of electroacupuncture and medication achieves the significant efficacy on Parkinson's disease combined with depression. This therapy regulates effectively serum BDNF level, relieves depression symptoms of the patients. The efficacy of electroacupuncture combined with medication is superior to the simple medication.

Impact of granulocytes on the antimicrobial effect of tedizolid in a mouse thigh infection model.

Tedizolid (TR-700, formerly torezolid) is the active component of the new oxazolidinone prodrug tedizolid phosphate (TR-701). We had previously demonstrated that tedizolid possessed potent antistaphylococcal activity superior to that of linezolid in a neutropenic mouse thigh infection model (A. Louie, W. Liu, R. Kulawy, and G. L. Drusano, Antimicrob. Agents Chemother. 55:3453-3460, 2011). In the current investigation, we used a mouse thigh infection model to delineate the effect of an interaction of TR-700 and granulocytes on staphylococcal cell killing. We compared the antistaphylococcal killing effect of doses of TR-701 equivalent to human exposures ranging from 200 to 3,200 mg/day in both granulocytopenic and normal mice. The mice were evaluated at 24, 48, and 72 h after therapy initiation. In granulocytopenic mice, a clear exposure response in which, depending on the time point of evaluation, stasis was achieved at "human-equivalent" doses of slightly below 2,300 mg/day (at 24 h) to slightly below 2,000 mg/day (at 72 h) was observed. In immune-normal animals, stasis was achieved at human-equivalent doses of slightly greater than 100 mg/day or less. The variance in bacterial cell killing results was attributable to the presence of granulocytes (without drug), the direct effect of TR-700 on Staphylococcus aureus, and the effect of the drug on Staphylococcus aureus mediated through granulocytes. The majority of the bacterial cell killing in normal animals was attributable to the effect of TR-700 mediated through granulocytes. Additional studies need to be undertaken to elucidate the mechanism underlying this observation.

In vivo pharmacodynamics of torezolid phosphate (TR-701), a new oxazolidinone antibiotic, against methicillin-susceptible and methicillin-resistant Staphylococcus aureus strains in a mouse thigh infection model.

Torezolid phosphate (TR-701) is the phosphate monoester prodrug of the oxazolidinone TR-700 which demonstrates potent in vitro activity against Gram-positive bacteria, including methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA). The pharmacodynamics of TR-701 or TR-700 (TR-701/700) against S. aureus is incompletely defined. Single-dose pharmacokinetic studies were conducted in mice for TR-701/700. Forty-eight-hour dose range and 24-hour dose fractionation studies were conducted in a neutropenic mouse thigh model of S. aureus infection using MRSA ATCC 33591 to identify the dose and schedule of administration of TR-701/700 that was linked with optimized antimicrobial effect. Additional dose range studies compared the efficacies of TR-701/700 and linezolid for one MSSA strain and one community-associated MRSA strain. In dose range studies, TR-701/700 was equally bactericidal against MSSA and MRSA. Mean doses of 37.6 and 66.9 mg/kg of body weight/day of TR-701/700 resulted in stasis and 1 log CFU/g decreases in bacterial densities, respectively, at 24 h, and mean doses of 35.3, 46.6, and 71.1 mg/kg/day resulted in stasis and 1 and 2 log CFU/g reductions, respectively, at 48 h. Linezolid administered at doses as high as 150 mg/kg/day did not achieve stasis at either time point. Dose fractionation studies demonstrated that the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) was the pharmacodynamic index for TR-701/700 that was linked with efficacy. TR-701/700 was highly active against MSSA and MRSA, in vivo, and was substantially more efficacious than linezolid, although linezolid's top exposure has half the human exposure. Dose fractionation studies showed that AUC/MIC was the pharmacodynamic index linked with efficacy, indicating that once-daily dosing in humans is feasible.

Dose range evaluation of Mycograb C28Y variant, a human recombinant antibody fragment to heat shock protein 90, in combination with amphotericin B-desoxycholate for treatment of murine systemic candidiasis.

Systemic candidiasis causes significant mortality in patients despite amphotericin B (AMB) therapy. Mycograb C28Y variant, a human recombinant antibody fragment to heat shock protein 90, is closely related to Mycograb, which showed a survival advantage in combination with AMB in a phase III human trial. The Mycograb C28Y variant could potentially increase the antifungal effect of AMB. In our study, the interaction between AMB-desoxycholate (DAMB) and the Mycograb C28Y variant was characterized in vitro by using a checkerboard method. Quantitative cultures of kidneys, livers, and spleens of neutropenic mice with systemic Candida albicans infections were used to assess the in vivo interaction between 1.4 mg/kg of body weight/day of DAMB and 0.15, 1.5, and 15 mg/kg/day of the Mycograb C28Y variant after 1, 3, and 5 days of therapy. DAMB and Mycograb C28Y variant monotherapies, vehicle, and a no-treatment arm served as controls. Also, single- and multidose pharmacokinetics for the Mycograb C28Y variant were determined. Indifference or synergy between DAMB and the Mycograb C28Y variant was seen in two trials by the checkerboard method. The pharmacokinetics of the Mycograb C28Y variant was best described by a 2-compartment model with a median serum t(1/2)(α) of ~0.198 h and a t(1/2)(ß) of ~1.77 h. In mice, DAMB together with the Mycograb C28Y variant was no more effective than AMB alone (P > 0.05 by analysis of variance). The Mycograb C28Y variant alone had no antifungal activity. We therefore conclude that the Mycograb C28Y variant in combination with DAMB offered no benefit over DAMB monotherapy in a neutropenic murine model of systemic candidiasis.