[Effect of individualized antihypertensive therapy on the blood pressure and left ventricular hypertrophy of hypertensive patients with coronary heart disease].

Objective: To investigate the effect of individualized antihypertensive therapy on the blood pressure and left ventricular hypertrophy (LVH) of hypertensive patients with coronary heart disease (CHD). Methods: We conducted a prospective study from Sep. 2014 to Dec. 2015 in Chinese PLA General Hospital. A total of 650 patients complicated with non-dipper or reverse-dipper hypertension and CHD were enrolled. All the participants were divided into non-dipper (n=259) and reverse-dipper (n=391) group according to their 24h ambulatory blood pressure monitoring (ABPM) reports. Patients who took short-acting antihypertensives changed their medicine to long-acting ones. Patients who had already taken long-acting antihypertensives switched to nighttime or added antihypertensives at night. Self-measured home blood pressure was recorded before going to bed and in the morning. All patients were regularly followed up by face-to-face surveys and clinic BP was recorded every 3 months. After 1 year's follow-up, the effect of individualized antihypertensive treatment on circadian rhythm of blood pressure was evaluated by 24h ABPM. The effect of individualized antihypertensive treatment on LVH was evaluated by echocardiography. Results: After 1 year's individualized antihypertensive therapy, the clinic BP and 24h ABPM of the patients were decreased. BP rhythm in 44% of the non-dipper and 57% of the reverse-dipper patients restored to normal. LVH were returned to normal in 44% of the non-dipper patients and and 48% of the reverse dipper patients, respectively. Left ventricular mass index (LVMI) were (59±12) kg/m(2.7) vs (48±10) kg/m(2.7) (P<0.01), and (63±13) kg/m(2.7) vs (48±11) kg/m(2.7) (P<0.01) respectively in non-dipper and reverse-dipper group before and after individualized antihypertensive treatment. Conclusion: Individualized antihypertensive intervention of abnormal blood pressure circadian rhythm can effectively restore the circadian rhythm of blood pressure and reverse LVH in hypertensive patients with CHD.

[Association between plasma microRNA-29a and left ventricular hypertrophy in patients with hypertension].

Objective: Previous studies have shown that plasma microRNA-29a (miRNA-29a) is associated with myocardial fibrosis and the degree of cardiac hypertrophy in patients with hypertrophic cardiomyopathy. However, the relationship between plasma miRNA-29a and hypertensive left ventricular hypertrophy (LVH) has not yet been reported. So the purpose of this study is to investigate the relationship between the plasma miRNA-29a and hypertensive LVH. Method: Enrolled 168 hypertensive patients and classified the patients into 2 groups: those with LVH (LVH group, n=41) and those without LVH (NLVH group, n=127). All patients underwent echocardiography examination. Left ventricular mass index (LVMI) was calculated by interventricular septal thickness (IVSd), left ventricular posterior wall thickness(LVPWTd), left ventricular end diastolic dimension (LVEDD) and left ventricular mass index (LVMI) were obtained. Plasma levels of miRNA-29a were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between plasma miRNA-29a levels and LVH was analyzed. Results: Plasma miRNA-29a was significantly higher in LVH group than in NLVH group (0.52±0.10 vs. 0.37±0.07, t=9.788, P<0.01) . Pearson correlation analysis evidenced a positive correlation between plasma miRNA-29a levels and IVSd(R=0.459, P<0.01), LVPWTd (R=0.398, P<0.01), and LVMI (R=0.745, P<0.01). After adjustment for gender, age, systolic blood pressure, diastolic blood pressure, body mass index, hypertension duration, antihypertensive drugs, multiple regression analysis showed that there were still positive correlations between plasma miRNA-29a level and IVSd (ß=0.535, P<0.01), LVPWTd (ß=0.085, P<0.01), and LVMI (ß=0.806, P<0.01). Conclusion: Plasma miRNA-29a level is positively associated with LVH in hypertensive patients, and future studies are warranted to explore if miRNA-29a could be used as a potential biomarker for LVH assessment in hypertensive patients.

[Circadian blood pressure characteristics in hospitalized unstable angina pectoris patients with hypertension].

Objective: To define the characteristic of circadian rhythm of blood pressure in unstable angina pectoris (UAP)patients with hypertension and its effects on the cardiovascular events. Methods: It was a prospective study.Based on coronary angiographic results, 742 consecutive hospitalized UAP patients with hypertension and 89 consecutive hospitalized hypertensive patients were recruited between September 2014 and December 2015 in this study. Clinical data and the results of 24-hour ambulatory blood pressure monitoring (ABPM) were analyzed. Results: The total prevalence of hypertension in UAP is about 77.1%(742/962) in our cohort. The decrease of night-time systolic and diastolic blood pressure in UAP patients complicated with hypertension was lower than that in hypertensive patients (P<0.05). The prevalence of dipper, non-dipper and reverse dipper pattern was 12.4%(92/742), 34.9%(259/742) and 52.7%(391/742) in UAP patients complicated with hypertension, 18.0%(16/89), 48.3%(43/89) and 33.7%(30/89) in hypertensive patients. Obviously, the abnormal circadian rhythm of blood pressure was more significant in UAP patients with hypertension than in hypertensive patients, characterized by higher reverse dipper pattern in UAP patients with hypertension compared to patients with hypertension(P=0.00), similar results were evidenced among the male and female patients and patients with various ages. Subgroup analysis showed that except similar results on the incidence of reverse dipper pattern in controlled blood pressure aged less than 45 years old, the incidence of reverse dipper pattern was all significantly higher in UAP patients complicating with hypertension than in hypertensive patients independent no matter blood pressure controlled or not (all P<0.05). After adjustment for sex, age, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and other risk factors, binary logistic regression analysis showed that reverse dipper pattern was independently associated with UAP(OR=1.53, 95%CI 1.12-2.61). Conclusions: This finding suggests that UAP patients with hypertension often have abnormal circadian rhythm, characterized by higher reverse dipper circadian pattern. Elevated nocturnal blood pressure is independently related to UAP.

[Effect of astaxanthin on vascular smooth muscle cells proliferation induced by platelet derived growth factor-BB].

OBJECTIVE: To investigate the effect of astaxanthin (AST) on vascular smooth muscle cells (VSMCs) proliferation in vitro induced by platelet derived growth factor-BB (PDGF-BB), and to explore its possible mechanism. METHODS: There were 4 groups in this experiment: blank control group, PDGF-BB group, PDGF-BB+ AST group, AST group. After the cells received different intervention for the indicated time, the cell growth was determined by Trypan blue staining; cell proliferation was demonstrated using CCK-8 kit; the cell cycle progression was analyzed by flow cytometry, and the mRNA expression of cyclin D1, cyclin E, CDK6, CDK4, cyclin kinase inhibitor protein P21 was determined by real-time PCR; reactive oxygen species (ROS) generation was detected using a Microplate reader; the total and phosphorylated forms of ERK1/2, p38 MAPK, JNK was observed in AST pretreated VSMCs in 5, 10 and 15 min after PDGF-BB treatment by Western blot analysis. RESULTS: (1) Cell viability: AST and/or PDGF-BB did not induce VSMCs necrosis with the different concentration compared with untreated cells (P>0.05). (2) Cell proliferation: PDGF-BB induced VSMCs proliferation (2.5±0.3 vs 1, P<0.01), while AST reversed the effect in a concentration-dependent manner when co-treated with PDGF-BB (all P<0.01); Cell cycle: Flow cytometry analysis showed that AST at a dose of 25 µmol/L reduced the percentages of cells in S phase and increased the G0/G1 populations in PDGF-BB-stimulated VSMCs; mRNA expression of the check-point proteins: Real Time PCR results demonstrated that, compared with the control group, the mRNA expression of CDK6, CDK4, cyclin D1, cyclin E in the PDGF-BB group was higher (4.20±0.30, 2.90±0.18, 3.50±0.30, 2.70±0.11 vs 1, all P<0.01), while p21 mRNA expression was lower (0.52±0.03 vs 1, P<0.01), while AST reversed these effects when co-treated with PDGF-BB. (3) ROS expression: compared with the control group, ROS level was significantly higher in the PDGF-BB group (2.10±0.09 vs 1, P<0.01), while AST reversed the effect in a concentration-dependent manner when co-treated with PDGF-BB (all P<0.01). (4) Signaling pathway: AST blocking the proliferation of VSMCs induced by PDGF-BB was related to suppress ERK1/2, p-p38 MAPK signaling pathway, but little effect to JNK. Conclutions: These results demonstrate that AST can block the proliferation and migration of VSMCs through G0/G1 to S phase of the cell cycle arrest. Further study indicates that AST suppress PDGF-BB-induced VSMCs proliferation is associated with an inhibition of ROS generation and ERK1/2, p-p38 MAPK signal pathways.

Morphological effects of the nanostructured ceria support on the activity and stability of CuO/CeO2 catalysts for the water-gas shift reaction.

Three CuO/CeO2 catalyst with different morphologies of ceria, namely nanospheres, nanorods and nanocubes, were synthesized and used to catalyze the water-gas shift (WGS) reaction. The reactivity tests showed that the Cu supported on the ceria nanospheres exhibited both the highest activity and superior stability when compared with the nanocube and nanorod ceria catalysts. Operando X-ray diffraction (XRD), X-ray absorption fine structure (XAFS) and diffuse reflectance Fourier transform infrared spectroscopy (DRIFTS) methods were used to characterize these catalysts in their working state. High resolution electron microscopy (HRTEM, STEM) was used to look at the local atomic structure and nano-scale morphology. Our results show that the morphology of the ceria support, which can involve different crystal faces and concentrations of defects and imperfections, has a critical impact on the catalytic properties and influences: (1) the dispersion of CuO in the as-synthesized catalyst; (2) the particle size of metallic Cu upon reduction during the WGS reaction, (3) the stability of the metallic Cu upon variations of temperature, and (4) the dissociation of water on the ceria support. The nanosphere ceria catalyst showed an excellent water dissociation capability, the best dispersion of Cu and a strong Cu-Ce interaction, therefore delivering the best performance among the three WGS catalysts. The metallic Cu, which is the active species during the WGS reaction, was more stabilized on the nanospheres than on the nanorods and nanocubes and thus led to a better stability of the nanosphere catalyst than the other two architectures. Each catalyst exhibited a distinctive line-shape in the 800-1600 cm(-1) region of the DRIFTS spectra, pointing to the existence of different types of carbonate or carboxylate species as surface intermediates for the WGS.

Cloning of a human nucleoside transporter implicated in the cellular uptake of adenosine and chemotherapeutic drugs.

In most mammalian cells nucleoside uptake occurs primarily via broad-specificity, es (e, equilibrative; 5, sensitive to NBMPR inhibition) transporters that are potently inhibited by nitrobenzylthioinosine (NBMPR). These transporters are essential for nucleotide synthesis by salvage pathways in hemopoietic and other cells that lack de novo pathways and are the route of cellular uptake for many cytotoxic nucleosides used in cancer and viral chemotherapy. They play an important role in adenosine-mediated regulation of many physiological processes, including neurotransmission and platelet aggregation, and are a target for coronary vasodilator drugs. We have previously reported the purification of the prototypic es transporter from human erythrocytes and have shown that this glycoprotein of apparent M, 55,000 is immunologically related to nucleoside transporters from several other species and tissues, including human placenta. Here we report the isolation of a human placental cDNA encoding a 456-residue glycoprotein with functional characteristics typical of an es-type transporter. It is predicted to possess 11 membrane-spanning regions and is homologous to several proteins of unknown function in yeast, nematodes, plants and mammals. Because of its central role in the uptake both of adenosine and of chemotherapeutic nucleosides, study of this protein should not only provide insights into the physiological roles of nucleoside transport but also open the way to improved therapies.

Biological modulations to facilitate graft healing in anterior cruciate ligament reconstruction (ACLR), when and where to apply? A systematic review.

BACKGROUND: When and where to apply the biological modulations is effective to promote healing in the anterior cruciate ligament (ACL) reconstruction remains unclear. PURPOSE: To perform a systematic review of preclinical animal studies on biological modulation in anterior cruciate ligament reconstruction (ACLR) concerning the time and site of delivery. STUDY DESIGN: Systematic review of controlled laboratory studies. METHODS: PubMed, Ovid, and Scopus were searched until December 2020 using a combination of keywords and their synonym to retrieve all animal studies about biological modulation in ACLR. Studies that assessed mechanical strength after ACLR and compared with negative control were included. The methodological quality of animal studies was evaluated. RESULTS: 33 studies were included in this review and the majority reported mechanical strength improvement. 79 â€‹% of studies applied the biological modulations intra-operatively with different delivery systems used. For 21 â€‹% of post-operative delivery studies, intermittent delivery was tried. 21 of the included studies directly applied the biological modulations in the bone tunnels, 5 studies applied intra-articularly while 7 studies applied both in the bone tunnels and intra-articular part. Biological modulations applied intra-operatively and those applied in both parts showed better mechanical strength increase. A shift of the failure mode of pull-out from the bone tunnel in the early healing phase, to mid-substance rupture in the later phase was observed in most studies. CONCLUSION: The improvement of the mechanical strength depends on how the biological modulations (delivery phase, delivery site, delivery form) are applied. The intra-operative delivery showed an overall higher mechanical strength increase and bone tunnel only delivery or intra-articular and bone tunnel both delivery are preferred than intra-articular only delivery. In addition, intra-articular and bone tunnel both delivery can have better mechanical strength increase for a long follow-up time. Thus, intra-operative application with a carrier to control release rate in both parts should be recommended. Further studies are needed to achieve a better healing outcome and more attention should be given to the intra-articular remodeling of the graft along with the tendon bone healing to increase the final mechanical strength. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Here, a systematic review of preclinical evidence of the time, site and the method the biological modulations being applied for ACLR to improve the graft healing would be performed. After reviewing the available studies, a choice of when and where to apply the biological modulations can achieve better mechanical strength after ACLR can be obtained. It provides evidence for both researchers and clinicians to decide when and where to apply the biological modulations can achieve their best effectiveness for ACLR before implementing. Promoting graft healing with targeted time and targeted site may reduce the risk of graft failure, safeguard return to sport.

Human equilibrative nucleoside transporter (ENT) family of nucleoside and nucleobase transporter proteins.

1. The human (h) SLC29 family of integral membrane proteins is represented by four members, designated equilibrative nucleoside transporters (ENTs) because of the properties of the first-characterized family member, hENT1. They belong to the widely distributed eukaryotic ENT family of equilibrative and concentrative nucleoside/nucleobase transporter proteins. 2. A predicted topology of eleven transmembrane helices has been experimentally confirmed for hENT1. The best-characterized members of the family, hENT1 and hENT2, possess similar broad permeant selectivities for purine and pyrimidine nucleosides, but hENT2 also efficiently transports nucleobases. hENT3 has a similar broad permeant selectivity for nucleosides and nucleobases and appears to function in intracellular membranes, including lysosomes. 3. hENT4 is uniquely selective for adenosine, and also transports a variety of organic cations. hENT3 and hENT4 are pH sensitive, and optimally active under acidic conditions. ENTs, including those in parasitic protozoa, function in nucleoside and nucleobase uptake for salvage pathways of nucleotide synthesis and, in humans, are also responsible for the cellular uptake of nucleoside analogues used in the treatment of cancers and viral diseases. 4. By regulating the concentration of adenosine available to cell surface receptors, mammalian ENTs additionally influence physiological processes ranging from cardiovascular activity to neurotransmission.

Gemcitabine transport in xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters.

BACKGROUND: Gemcitabine, a pyrimidine analogue of deoxycytidine, is an anticancer nucleoside drug that requires functional plasma membrane nucleoside transporter proteins to reach its intracellular targets and cause cytotoxicity. Because of technical difficulties inherent in studying nucleoside transport in human cells, we rigorously defined gemcitabine membrane transportability by producing each of the available human (h) and rat (r) recombinant nucleoside transporters (NTs) individually in Xenopus laevis oocytes. METHODS: Oocytes were microinjected with in vitro-transcribed RNAs derived from complementary DNAs encoding (C = concentrative) rCNT1, rCNT2, hCNT1, hCNT2, (E = equilibrative) rENT1, rENT2, hENT1, and hENT2. Uptake of [(3)H]gemcitabine and [(14)C] uridine was measured 3 days after microinjection to determine kinetic constants. We also used the two-electrode, voltage-clamp technique to investigate the electrophysiology of hCNT1-mediated gemcitabine transport. RESULTS: Gemcitabine was transported by most of the tested proteins (the exceptions being the purine-selective rCNT2 and hCNT2), with the greatest uptake occurring in oocytes producing recombinant rCNT1 and hCNT1. Influxes of gemcitabine mediated by hCNT1, hENT1, and hENT2 were saturable and conformed to Michaelis-Menten kinetics with apparent K(m) values of 24, 160, and 740 microM, respectively. Gemcitabine had a limited ability to cross the lipid bilayer of oocyte membranes by simple diffusion. External application of gemcitabine to oocytes producing recombinant hCNT1 induced an inward current, which demonstrated that hCNT1 functions as a Na(+)/nucleoside co-transport protein and confirmed the transporter's ability to transport gemcitabine. CONCLUSIONS: Mammalian nucleoside transporters vary widely in their affinity and capacity to transport gemcitabine. Variation in the tumor and tissue distribution of plasma membrane nucleoside transporter proteins may contribute to the solid tumor activities and schedule-dependent toxic effects of gemcitabine.

Pilot study to examine the effect of antibiotic therapy on MRI outcomes in RRMS.

This trial examined the safety and possible MRI and clinical effects of anti-chlamydial antibiotic therapy in relapsing-remitting MS (RRMS). Newly diagnosed MS patients were selected to participate if they showed Chlamydia pneumoniae gene in their CSF and had one or more enhancing lesions on brain magnetic resonance imaging (MRI). After a 4-month run in phase of monthly MRI, patients were randomized to receive rifampin (300 mg twice daily) and azithromycin (500 mg every other day) for 6 months or placebo (PBO). Patients then had monthly MRI on therapy and two additional scans on months 12 and 14. Lumbar punctures were repeated between months 7 and 8 and within 2 weeks of termination of the study. Data on 4 patients on treatment and 4 on PBO were available for analysis. The primary outcome measure of showing a beneficial effect on enhancing lesions was not met. However, there was a significant difference in brain parenchymal fraction loss favoring those patient receiving antibiotics compared with PBO (p< or =0.02). Three of the four patients on antibiotic therapy cleared the organism from the CSF by month 12; in the PBO group one patient cleared the organism. The reduction in atrophy in patients receiving antibiotics must be viewed with caution, due to the small number of patients studied.

Regulation by IFN-beta of inducible nitric oxide synthase and interleukin-12/p40 in murine macrophages cultured in the presence of Chlamydia pneumoniae antigens.

Chlamydia pneumoniae has been demonstrated in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS). Interferon-beta (IFN-beta) has favorable effects on the clinical course of MS. We investigated whether the beneficial effects of IFN-beta in MS may involve its role in regulating nitric oxide (NO) and interleukin-12 (IL-12) in macrophages, as these immune modulators form part of the innate immune response to intracellular pathogens, such as C. pneumoniae. Murine macrophages in cultures exposed to elementary body antigens or recombinant major outer membrane protein (rMOMP) of C. pneumoniae demonstrate a significant increase in NO as well as production of IL-12/p40 in culture supernatants compared with basal levels. Addition of murine IFN-beta increased NO activity in murine macrophages cultured with chlamydial antigens. Addition of neutralizing anti-IFN-beta antibody prevented the NO increase. In contrast to its effect on inducible NO synthase (iNOS), IFN-beta reduced induction of IL-12/p40 following culture with either elementary body antigens or rMOMP. Inhibition was reversed with anti-IFN-beta antibody. If C. pneumoniae infection is responsible for the inflammatory response in the pathogenesis of MS, the beneficial effects of IFN-beta in MS may be due to its enhancing intracellular NO activity while inhibiting secretion of the proinflammatory cytokine, IL-12.

CSF oligoclonal bands in MS include antibodies against Chlamydophila antigens.

BACKGROUND: Considerable evidence suggests the role of an infectious agent in MS. The presence of Chlamydophila pneumoniae in CSF from patients with MS was shown earlier; to further examine this association the reactivity of the oligoclonal antibody response in the CSF of patients with MS to C pneumoniae antigens was determined and compared with other antigens. METHODS: Seventeen patients with MS and 14 control subjects with other neurologic disease were studied. Affinity-driven immunoblot studies and solid-phase adsorption of CSF oligoclonal bands by elementary body antigens of C pneumoniae, viral antigens (measles and herpes simplex virus-1), bacterial antigen (Escherichia coli and Staphylococcus aureus), and heat shock protein-60 were performed. RESULTS: Affinity-driven immunoblot studies demonstrated reactivity of oligoclonal bands in CSF samples from 16 patients with MS against elementary body antigens of C pneumoniae. None of the control subjects showed a prominent reactivity to elementary body antigens of C pneumoniae. In 14 of 17 patients with MS examined, oligoclonal bands were adsorbed either partially or completely from the CSF by elementary body antigens of C pneumoniae, but not by myelin basic protein, heat shock protein-60, or bacterial or viral antigens. In three patients with subacute sclerosing panencephalitis, adsorption of oligoclonal bands was seen with measles virus antigens but not with elementary body antigens of C pneumoniae. CONCLUSIONS: Oligoclonal bands in CSF of patients with MS include antibodies against Chlamydophila antigens.

Demonstration of system y+L activity on the basal plasma membrane surface of rat placenta and developmentally regulated expression of 4F2HC mRNA.

Na(+)-independent cationic amino acid transport in the rat placenta occurs by leucine-sensitive and leucine-insensitive pathways. The ontogeny of these transport mechanisms within the rat placenta has been described recently. To assign the leucine-inhibitable portion of uptake definitively the uptake of [3H]arginine was studied in the presence of both BCH (to inhibit system Bo,+) and varied concentrations of leucine. Uptake of arginine into basal-enriched membrane vesicles derived from rat placenta was, in the presence of sodium, inhibited by micromolar concentrations of leucine, consistent with assignment of this activity to system y+L. In contrast, the majority of arginine uptake into apical-enriched membrane vesicles was leucine insensitive. Messenger RNA derived from rat placenta at days 14, 16, 18 and 20 of gestation was hybridized with full-length rat cDNA probes against NBAT and 4F2HC (thought to encode proteins associated with system bo,+ and y+L activities, respectively). No NBAT mRNA was detected, whereas 4F2HC mRNA was present at all gestational stages, increasing 12-fold over the last third of gestation. It is concluded that system y+L is present in the basal plasma membrane of the rat placenta syncytium and is subject to developmental regulation by a mechanism that alters the steady content of 4F2HC mRNA.

Studies on the control of hookworm and other soil-transmitted helminthiases in farmers in Zhejiang Province, China.

Different periodic selective chemotherapeutic schemes were used to control hookworm and other soil-transmitted helminthiases in eight villages in five counties in Zhejiang Province, China, 1985-1988. The results showed that the prevalence rates of hookworm, ascariasis, and trichuriasis decreased from 35.0-74.4%, 47.0-.76% and 22.9-47.5% to 3.2-15.8%, 9.9-47.8%, and 3.5-31.2%, respectively, using pyrantel pamoate (10 mg/kg for 1-2 days) or albendazole (400 mg for 1-2 days, once or twice a year for 2-3 years). The eggs per gram of feces of hookworm and Trichuris trichiura also dropped markedly after control. Moreover, the mean hemoglobin levels of sampled populations increased after several treatments. The authors recommend periodic selective chemotherapy as the main method to control soil-transmitted helminthiases, especially hookworm infections.

[Longitudinal observation on the control of intestinal helminthiasis].

OBJECTIVE: To search suitable measure for rapid control intestinal helminthiasis and long-term strengthen efficacy. METHODS: The treatment was taken in egg-positive population of intestinal helminthiasis in 1986-1988. The treatment was carried out only in the selected population in 1989-1992. No measure was taken in 1993-2000. RESULTS: (1) The prevalence rate of hookworm, Ascaris and Trichuris decreased to 3.2%, 37.3% and 3.5% respectively after administration of albendazole twice a year for 3 years. (2) The prevalence rate of hookworm continued to decrease to 0.5% after treatment on selected population. (3) The prevalence rate and the intensity of hookworm has been less than 1% and 10/LPG for 8 years. No hookworm larvae had been isolated from the soil. CONCLUSION: The hookworm transmission was effectively controlled in the study site.

[Clinical observation on efficacy of ivermectin in the treatment of intestinal nematode infections].

A total of 166 cases were divided into 3 groups: group A comprised 55, group B 54 and group C 57 cases. Group A received ivermectin 0.1 mg/kg orally at a single dose, the cure rates were 100%, 3.8% and 50% for ascaris, hookworm and trichuris, infections respectively: group B received ivermectin 0.2 mg/kg orally at a single dose, the corresponding cure rates were 95.5%, 11.8% and 76.5% respectively; group C received pyrantel pamoate 10 mg/kg orally at a single dose, the corresponding cure rates were 95.5%, 29.6% and 31.6% respectively. Although the cure rates were very low for hookworm infection in both group A and B, however, a number of adult worms of Ancylostoma duodenale and Necator americanus were expelled aster medication; It indicates that ivermectin has some effects on these two species of human hookworm. Side effects were mild and transient in all groups.

[Implementation of a software for acquiring and analysing myoelectric potential signals in ergonomical research of space manual system].

Objective. A software used for acquiring and analyzing signals was developed for ergonomical research on Human Workload in space manual system. Method. As an important part of the whole experimental equipment and being developed in PC, the software is composed of acquisition and display program, analysis and processing program and data files. Result. The software is capable of making realtime acquisition and display of four channels of myoelectric potential signals and one channel of operation signal synchronously. The signals are then analyzed and processed off-line. Conclusion. During the development, its realtime feature was implemented by means of some technical methods, such as that different machine assigned to view-scenery display and signal acquisition, different frequency assigned to EMG signal and operation ones, and different cycle assigned to acquisition, display and storage. Above all, with friendly man-machine interface and high accuracy of data, the software was even reliable.

nNOS mediated mitochondrial injury in LPS stimulated oligodendrocytes.

Products of inflammation and the activation of nitric oxide synthase have been proposed as a mechanism of oligodendrocyte injury in CNS inflammation. There are currently three well described and known isoforms of NOS. Of these, neuronal NOS (nNOS) was initially discovered in neurons, endothelial NOS (eNOS) in vascular endothelium, while the inducible form of NOS (iNOS) is known to be activated in oligodendrocytes, astrocytes and microglia. We examined the activation of nNOS and the down stream effects of NO production in oligodendrocyte precursor cells (OPC) and MO3.13 cell line following culture with LPS. Our studies show that both MO3.13 cells and OPC are susceptible to the cellular injury resulting from LPS mediated activation and NO production. Activation of the TLR4 receptor with LPS led to decrease in cell viability that was associated with loss of mitochondrial membrane potential and impaired enzymatic activity of complex I and complex IV protein of the respiratory chain. 7-NI, a known inhibitor of nNOS was able to rescue of cells from LPS mediated mitochondrial damage. Loss of mitochondrial function was associated with translocation of cytochrome C and apoptosis inducing factor to the cytosol, setting the stage for apoptosis. Phosphorylation of PI3K and Akt was required for optimal activation of NOS. These studies provide a biochemical basis for nNOS mediated oligodendrocyte injury and suggest similar mechanisms may play a role in diseases characterized by oligodendrocyte loss and demyelination.

In vitro and in vivo induction and activation of nNOS by LPS in oligodendrocytes.

There are currently four known isoforms of nitric oxide synthase (NOS). Of these, neuronal NOS (nNOS) is known to be present exclusively in neurons, endothelial NOS (eNOS) in vascular endothelium, while the inducible form of NOS (iNOS) is known to be activated in oligodendrocytes, astrocytes and microglia. The fourth isoform, mitochondrial NOS (mtNOS), represents a post-translational modification of nNOS. Using western blotting and real time-PCR, we show induction and activation of nNOS following culture of oligodendrocyte progenitor cells (OPC) with lipopolysaccharide (LPS). Activation of nNOS results in accumulation of peroxynitrite and tyrosine nitration of proteins in oligodendrocytes resulting in reduced cell viability. Injection of LPS in vivo into the corpus callosum of rats leads to the development of extensive demyelination of the white matter tracts. Immunostaining of regions close to the injection site shows the presence of nNOS, but not iNOS, in oligodendrocytes. Neither iNOS nor nNOS was seen in astrocytes in areas of demyelination. These studies suggest that activation of nNOS in oligodendrocytes leads to oligodendrocyte injury resulting in demyelination.