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Therapeutic Effects (therapeutic + effects)
Kinds of Therapeutic Effects Selected AbstractsTherapeutic Effects of Anti-FGF23 Antibodies in Hypophosphatemic Rickets/Osteomalacia,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2009Yukiko Aono Abstract X-linked hypophosphatemia (XLH), characterized by renal phosphate wasting, is the most common cause of vitamin D-resistant rickets. It has been postulated that some phosphaturic factor plays a causative role in XLH and its murine homolog, the Hyp mouse. Fibroblast growth factor 23 (FGF23) is a physiological phosphaturic factor; its circulatory level is known to be high in most patients with XLH and Hyp mice, suggesting its pathophysiological role in this disease. To test this hypothesis, we treated Hyp mice with anti-FGF23 antibodies to inhibit endogenous FGF23 action. A single injection of the antibodies corrected the hypophosphatemia and inappropriately normal serum 1,25-dihydroxyvitamin D. These effects were accompanied by increased expressions of type IIa sodium-phosphate cotransporter and 25-hydroxyvitamin-D-1,-hydroxylase and a suppressed expression of 24-hydroxylase in the kidney. Repeated injections during the growth period ameliorated the rachitic bone phenotypes typically observed in Hyp mice, such as impaired longitudinal elongation, defective mineralization, and abnormal cartilage development. Thus, these results indicate that excess actions of FGF23 underlie hypophosphatemic rickets in Hyp mice and suggest a novel therapeutic potential of the FGF23 antibodies for XLH. [source] Therapeutic Effects and Anti-inflammatory Mechanisms of Heparin on Acute Lung Injury in RabbitsACADEMIC EMERGENCY MEDICINE, Issue 7 2008Meitang Wang MD Abstract Objectives:, The objectives were to investigate the potential beneficial effects and molecular mechanisms of heparin and low-molecular-weight heparin (LMWH) on acute lung injury (ALI). Methods:, Forty-eight rabbits were randomized into four groups: normal control group (Group A), lipopolysaccharide (LPS) group (Group B), LPS + heparin group (Group C), and LPS + LMWH group (Group D). The rabbit ALI model was established by intravenous (IV) injection with LPS. Alveolar,arterial O2 difference (PA-aO2), serum tumor necrosis factor , (TNF-,), circulating p38 mitogen-activated protein kinase (p38 MAPK) levels, lung nuclear factor (NF)-,B levels, and lung dry/wet (D/W) ratio were measured, and the lung injury scores were calculated. Results:, Lipopolysaccharide caused significant increases in PA-aO2, serum TNF-,, expression of p38 MAPK in polymorphonuclear neutrophils (PMNs), the lung injury scores, and nuclear factor-,B (NF-,B) activity in the lung tissue and caused a decrease in lung D/W ratio. A positive linear correlation was found between p38 MAPK and TNF-, at 1, 2, 4, and 6 hours (r = 0.68, 0.92, 0.93, and 0.93, respectively) and between NF-,B and p38 MAPK and TNF-, at 6 hours (r = 0.94 and 0.83, respectively). IV heparin or LMWH given after LPS treatment attenuated these changes in inflammatory response, oxygenation, p38 MAPK expression, and NF-,B activation. Conclusions:, The anti-inflammatory mechanisms of heparin in ALI may be inhibiting p38 MAPK and NF-,B activities, and then TNF-, overexpression, thus alleviating the inflammatory reaction. [source] Therapeutic effects of functional electrical stimulation of the upper limb of eight children with cerebral palsyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 11 2000P A Wright BSc PhD Functional electrical stimulation (FES) of the upper limb has been used for patients with a variety of neurological conditions, although few studies have been conducted on its use on the upper limb of children with cerebral palsy (CP). The aim of this study was to investigate the effect of cyclic FES on the wrist extensor muscles of a group of eight children (five boys, three girls) with hemiplegic CP (mean age 10 years). The study design involved a baseline (3 weeks), treatment (6 weeks), and follow-up (6 weeks). FES was applied for 30 minutes daily during the treatment period of the study. Improvements in hand function (p,0.039) and active wrist extension (p=0.031) were observed at the end of the treatment period. These improvements were largely maintained until the end of the follow-up period. No significant change was observed in the measurements of wrist extension moment during the treatment period (p=0.274). Hand function in this group of children improved after they were exposed to FES of wrist extensor muscles. This suggests that FES could become a useful adjunct therapy to complement existing management strategies available for this patient population. [source] Therapeutic effects of complex rearing or bFGF after perinatal frontal lesionsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2008Wendy Comeau Abstract We investigated the effects of an enriched environment and/or basic fibroblast growth factor (bFGF) on recovery from neonatal frontal injury in rats. Rats received medial frontal lesions, or sham surgery, on postnatal day (P) 2/3. In the first set of experiments (Experiments 1 and 2), rats were housed in enriched environments that consisted of a large enclosure with multiple objects (or standard housing) for 90 days beginning at weaning (P22) or in adulthood (P110). In Experiment 3, the rats either received 7 days of subcutaneous bFGF beginning on the day after surgery or bFGF plus enriched housing beginning at weaning. After the 90-day housing period, the animals were tested on a spatial navigation task and a skilled reaching task. Early lesions of the medial frontal cortex caused severe impairments in spatial learning but this deficit was markedly reduced with enriched housing, bFGF, or a combination of both, with the latter being most effective. The housing effects varied with age, however: the earlier the experience began, the better the outcome. Enriched housing increased dendritic length in cortical pyramidal neurons, an effect that was greater in the lesion than the control animals, and enriched housing reversed the lesion-induced decrease in spine density. Enriched environment increased the thickness of the cortical mantle in both lesion and controls whereas bFGF had no effect. Experience thus can affect functional and anatomical outcome after early brain injury but the effects vary with age at experience and may be facilitated by treatment with bFGF. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 134,146, 2008. [source] Contrasting Effects of Zonisamide and Acetazolamide on Amygdaloid Kindling in RatsEPILEPSIA, Issue 11 2001Koichi Hamada Summary: ,Purpose: Zonisamide (ZNS) and acetazolamide (AZM) are two antiepileptic drugs (AEDs) that differ in clinical efficacy. To elucidate the mechanisms of action of these compounds, we investigated their therapeutic and prophylactic effects in rats by using a kindling model of partial epilepsy. Methods: Electrodes were implanted into the left amygdala of adult male Wistar rats. The animals were stimulated at the afterdischarge threshold until five stage 5 seizures were induced. The generalized seizure threshold was then determined. Therapeutic effects were examined in rats manifesting successive convulsions with near-threshold stimulation. To test prophylactic effects, drugs were administered intraperitoneally before daily kindling stimulation until the animal had a stage 5 seizure or reached day 18. Results: ZNS (10,40 mg/kg; n = 6) suppressed kindled seizures in a dose-dependent manner. Repeated administration for 7 days produced tolerance to anticonvulsive effects. AZM (25,200 mg/kg; n = 7) showed limited therapeutic effect, alleviating only the clonic convulsion in stage 5 seizures and reducing afterdischarge duration. Secondary generalization was not significantly suppressed during repeated treatment (50,200 mg/kg; n = 6). ZNS, 25 or 40 mg/kg (n = 8), significantly retarded seizure development; 15.0 or 17.0 daily stimulations were required to produce a stage 5 seizure. AZM, 50,200 mg/kg (n = 6), also retarded seizure development, with 14.0,14.8 stimulations required. Conclusions: ZNS exhibited modest therapeutic and prophylactic effects, whereas AZM showed mainly prophylactic effects. Hypotheses are presented that may explain the mechanisms of action of these drugs. [source] Therapeutic effects of a new lymphocyte homing reagent FTY720 in interleukin-10 gene-deficient mice with colitisINFLAMMATORY BOWEL DISEASES, Issue 3 2004Tsunekazu Mizushima MD Abstract Background: FTY720 is a novel reagent that possesses potent immunosuppressive activity. The immunosuppression induced by FTY720 is mediated by completely different mechanisms from those of conventional immunosuppressants, that is, by altering the tissue distribution of lymphocytes rather than inhibiting activation. In this study, we examined the efficacy of FTY720 in the treatment of chronic colitis in an interleukin-10 gene-deficient (IL-10,/,) mouse model. Methods: FTY720 was administered orally for 4 weeks to IL-10,/,mice with clinical signs of colitis. The gross and histologic appearance of the colon and the numbers, phenotype, cytokine production, and apoptosis of lymphocytes were compared with those characteristics in a control group. Results: Single-dose administration of FTY720 resulted in the sequestration of circulating lymphocytes within the secondary lymphoid tissues. Four-week administration resulted in a significant reduction of the CD4+ T lymphocytes subpopulation in the colonic lamina propria and IFN-, production of the colonic lymphocytes, accompanied by a significant decrease in the severity of colitis. Conclusions: Treatment of established colitis in IL-10,/, mice with FTY720 ameliorated the colitis, probably as a result of decreasing the number of lymphocytes in the colonic mucosa and an associated reduction in IFN-, production. [source] 99mTc-MIBI imaging for prediction of therapeutic effects of second-generation MDR1 inhibitors in malignant brain tumorsINTERNATIONAL JOURNAL OF CANCER, Issue 12 2007Toshio Sasajima Abstract The aim of this study was to explore whether 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) is suitable to elucidate multidrug resistance and prediction of potentiation of antitumor agents by second-generation MDR1 inhibitors (PSC833, MS-209) in malignant brain tumors in rat. Malignant tumor cells (RG2 and C6 gliomas, Walker 256 carcinoma) were incubated with low dose vincristine (VCR) to induce multidrug resistance. MTT assay demonstrated a significant increase of surviving fractions in VCR-resistant sublines compared to those of drug-naive cells. Reverse transcriptase polymerase chain reaction revealed higher expression of MDR1 mRNA in VCR-resistant cells than drug-naive cells in each line. Volume distribution (Vd) of 99mTc-MIBI was negatively correlated with MDR1 mRNA expression among drug-naive and VCR-resistant cells. MDR1 inhibitors decreased surviving fractions and increased Vd of 99mTc-MIBI significantly in VCR-resistant sublines, whereas MDR1 mRNA expression was unchanged. These findings indicate that 99mTc-MIBI efflux was functionally suppressed by MDR1 inhibitors. Autoradiographic images of 99mTc-MIBI revealed higher uptake in drug-naive cells at basal ganglia compared with VCR-resistant cells at the opposite basal ganglia of rats. Oral administration of the second-generation MDR1 inhibitors significantly increased 99mTc-MIBI accumulation of both tumors. Therapeutic effects of VCR with or without the MDR1 inhibitors were also evaluated autoradiographically using 14C-methyl- L -methionine (14C-Met) and MIB-5 index. 14C-Met uptake and MIB-5 index of both tumors treated with VCR following the MDR1 inhibitor treatment significantly decreased compared with tumors treated with VCR alone. Analysis of 99mTc-MIBI accumulation is considered informative for detecting MDR1-mediated drug resistance and for monitoring the therapeutic effects of MDR1 inhibitors in malignant brain tumors. © 2007 Wiley-Liss, Inc. [source] Therapeutic effects of long-term administration of an oral adsorbent in patients with chronic renal failure: two-year studyINTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2005NOBUYOSHI TAKAHASHI Abstract Background:, Kremezin is an oral adsorbent that attenuates the progression of chronic renal failure by removing uremic toxins and their precursors from the gastrointestinal tract. Previously two clinical studies based on reciprocal serum creatinine levels (1/Scr) have confirmed the efficacy of Kremezin (Kureha Chemical, Tokyo, Japan) in undialyzed patients who had been followed up for 6 months or 1 year. This is the first report to evaluate the therapeutic effects of long-term administration (2 years.) of Kremezin in undialyzed patients. Methods:, Kremezin was given to 48 enrolled undialyzed patients with a median Scr level of 4.3 mg/dL. Rates of decline of 1/Scr, as well as the time for Scr level to reach 10 mg/dL, the critical value requiring dialysis, were compared before and after administration of Kremezin. Results:, During the 2-year therapeutic period, 1/Scr gradients were significantly attenuated (P = 0.0083), and the estimated time to dialysis was prolonged from 16.3 ± 16.3 months to 29.8 ± 24.1 months (P = 0.002). When the patients were divided into two groups, based on of systolic blood pressure (SBP), defined by the World Health Organization (WHO) classification, a significantly smaller number of patients in the low blood pressure group (SBP < 160 mmHg) were introduced to dialysis (P = 0.0005), and the estimated time to dialysis was significantly extended in the low blood pressure group (P = 0.0125). Conclusion:, In addition to the control of blood pressure in undialyzed patients, Kremezin has additive salutary effects to halt the progressive loss of renal function, resulting in the delay of dialysis. [source] Therapeutic effects of interleukin-6 blockade in a murine model of polymyositis that does not require interleukin-17AARTHRITIS & RHEUMATISM, Issue 8 2009Naoko Okiyama Objective To explore new molecular targets in the treatment of polymyositis (PM) by examining a recently established murine model of PM, C protein,induced myositis (CIM), for involvement of an interleukin-6 (IL-6)/IL-17A pathway. Methods CIM was induced by immunizing wild-type mice as well as IL-6,null and IL-17A,null C57BL/6 mice with recombinant mouse skeletal C protein fragments. Some mice were treated with anti,IL-6 receptor (anti,IL-6R) monoclonal antibodies or control antibodies. Muscle tissue samples were examined histologically and immunohistochemically. Results The syngeneic C protein fragments successfully induced inflammation in the skeletal muscles of wild-type mice. IL-6 was expressed by mononuclear cells, especially in macrophages, infiltrating in the muscles. IL-6,null mice developed myositis with significantly lower incidence and milder severity than wild-type mice. In contrast, IL-17A,null mice were as susceptible to CIM as wild-type mice. Intraperitoneal administration of anti,IL-6R monoclonal antibodies, but not of control monoclonal antibodies, ameliorated CIM both preventively and therapeutically. Conclusion Our findings indicate that IL-6 is critically involved in the development of CIM. Although many other autoimmune models require IL-6 for differentiation of pathogenic T cells producing IL-17A, IL-17A was dispensable in CIM. Nevertheless, treatment with anti,IL-6R antibodies was effective. IL-6 blockade is potentially a new approach to the treatment of autoimmune myositis, via processes distinct from interference in the IL-6/IL-17A pathway. [source] Therapeutic effects of rifampin and erythromycin in experimental murine brucellosisCLINICAL MICROBIOLOGY AND INFECTION, Issue 2 2000S. Felek [source] A patch test study of 27 crude drugs commonly used in Chinese topical medicamentsCONTACT DERMATITIS, Issue 1 2003Hsuan-Hsiang Chen Chinese topical medicaments (CTMs) are commonly used in Taiwan and in Southeast Asia. However, a systematic evaluation of contact sensitization potential from CTM has not been carried out to our knowledge. This study was undertaken to investigate the incidence of contact sensitivity to the components of CTM in patients with contact dermatitis from CTM. A screening series of 27 crude drugs most commonly used in CTM as well as a modified European standard series was patch tested in 30 patients. The herbs with the most frequent positive reactions were Flos Caryophylli ( ), Radix Angelicae Pubescentis ( ), Cortex Cinnamomi ( ), Cortex Radix Acanthopanacis ( ), Caulis Impatientis ( ), Resina Draconis/Sanguis Draconis ( ), Fructus Cnidii ( ), Radix Gentiana Macrophyllae ( ), and Rhizoma Ligustici Chuanxiong ( ). Concomitant allergy to colophonium was found in most of these positive reactions. Reducing the concentration and simplifying the compositions of these components, as well as replacement with those of low allergenicity in CTM, such as Rhizoma Arisaematis ( ), Herba Lycopodii ( ), Radix Cyathulae Officinalis ( ), Rhizoma Pinelliae ( ), Radix Angelicae Dahuricae ( ), Herba Dendrobii ( ), Secretio Moschus ( ), and Stigmata Croci ( ), may be advocated. A precise labelling of the dosage of each component and the exact chemical compounds in CTM products could further improve the safety and therapeutic effects of CTM in the future. [source] Mechanisms of change in motivational interviewing: a review and preliminary evaluation of the evidenceADDICTION, Issue 5 2009Timothy R. Apodaca ABSTRACT Aims Motivational interviewing (MI) is an efficacious treatment for substance use disorders. However, little is known about how MI exerts its therapeutic effects. This review is a first attempt to summarize and evaluate the evidence for purported within-session mechanisms of change. The primary question of interest was: which MI constructs and variables appear to be the most promising candidates for mechanisms of change? Methods Literature searches were conducted to identify studies delivering MI in an individual format for the treatment of substance use disorders. Our search identified a total of 152 studies for review; 19 studies met inclusion criteria by providing data on at least one link in the causal chain model under examination. Effect size estimates were calculated for every possible step in the causal model where sufficient data were provided by study authors. Results Four constructs of therapist behavior were evaluated: MI-Spirit, MI-Consistent behaviors, MI-Inconsistent behaviors and therapist use of specific techniques. Five constructs of client behavior were evaluated: change talk/intention, readiness to change, involvement/engagement, resistance and the client's experience of discrepancy. The absence of experimental and full mediation studies of mechanisms of change was notable. Effect sizes were generally mixed. Conclusions The most consistent evidence was found for three constructs: client change talk/intention (related to better outcomes); client experience of discrepancy (related to better outcomes); and therapist MI-Inconsistent behavior (related to worse outcomes). Regarding therapist use of specific techniques, use of a decisional balance exercise showed the strongest association to better outcomes. [source] Intravenous and intratracheal administration of trimetoquinol, a fast-acting short-lived bronchodilator in horses with ,heaves'EQUINE VETERINARY JOURNAL, Issue 6 2006F. C. CAMARGO Summary Reason for performing study: Trimetoquinol (TMQ) is a potent ,-adrenoceptor agonist bronchodilator used in human medicine but has not been evaluated for potential use as a therapeutic agent for horses with ,heaves'. Objectives: To assess the pharmacodynamics of TMQ in horses with ,heaves' to determine potential therapeutic effects. Methods: Increasing doses of TMQ were administered to horses with ,heaves' by i.v. and intratracheal (i.t.) routes. Doses ranged 0.001,0.2 ,g/kg bwt i.v. and 0.01,2 ,g/kg bwt i.t. Cardiac and airways effects were assessed by measurement of heart rate (HR) and maximal change in pleural pressure (,Pplmax), respectively. Side effects of sweating, agitation and muscle trembling were scored subjectively. Duration of action to i.v. (0.2 ,g/kg bwt) and i.t. (2 ,g/kg bwt) TMQ was evaluated over 6 h. Results: Intravenous TMQ was an exceptionally potent cardiac stimulant. Heart rate increased at 0.01 ,g/kg bwt, and was still increasing after administration of highest dose, 0.2 ,g/kg bwt. Airway bronchodilation, measured as a decrease in ,Pplmax, also commenced at 0.01 ,g/kg bwt. By the i.t. route, TMQ was 50,100-fold less potent than by i.v. Side effects included sweating, agitation and muscle trembling. Overall, the onset of HR and bronchodilator effects was rapid, within about 3 min, but effects were over at 2 h. Conclusion: When administered i.v. and i.t., TMQ is a highly potent cardiac stimulant and a modest bronchodilator. It may not be an appropriate pharmacological agent by i.v. and i.t. routes for the alleviation of signs in horses with ,heaves'. Further studies of TMQ by oral and aerosol routes are necessary. Potential relevance: In horses, TMQ is a fast-acting bronchodilator with a short duration of action. It could be used as a rescue agent during an episode of ,heaves'. The i.v. and i.t. administration of TMQ is associated with side effects, similar to those reported for all other ,-agonists. However, other routes, such as aerosol and oral, may prove useful and safe for the alleviation of bronchoconstriction typical of ,heaves'. [source] IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2007Wanda Niedbala Abstract Epstein-Barr virus-induced gene,3 (EBI3) and the p35 subunit of IL-12 have been reported to form a heterodimeric hematopoietin in human and mouse. We have constructed a heterodimeric protein covalently linking EBI3 and p35, to form a novel cytokine which we now call IL-35. The Fc fusion protein of IL-35 induced proliferation of murine CD4+CD25+ and CD4+CD25, T cells when stimulated with immobilized anti-CD3 and anti-CD28 antibodies in vitro. The IL-35-expanded CD4+CD25+ T cell population expressed Foxp3 and produced elevated levels of IL-10, whereas the IL-35-induced CD4+CD25, T cells produced IFN-, but not IL-4. The in vitro expanded CD4+CD25+ T cells retained their suppressive functions against CD4+CD25, effector cells. Furthermore, when cultured with soluble anti-CD3 antibody and antigen-presenting cells, IL-35 suppressed the proliferation of CD4+CD25, effector cells. Moreover, IL-35 inhibited the differentiation of Th17 cells in vitro. In vivo, IL-35 effectively attenuated established collagen-induced arthritis in mice, with concomitant suppression of IL-17 production but enhanced IFN-, synthesis. Thus, IL-35 is a novel anti-inflammatory cytokine suppressing the immune response through the expansion of regulatory T cells and suppression of Th17 cell development. [source] Molecular Interaction between a Gadolinium,Polyoxometalate and Human Serum AlbuminEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 34 2009Li Zheng Abstract Polyoxometalates (POMs) show promising antibacterial, antiviral (particularly anti-HIV), antitumor, and anticancer activities, but the mechanism of these potential therapeutic effects remains to be elucidated at the molecular level. The interaction between the Gd-containing tungstosilicate [Gd(,2 -SiW11O39)2]13, and human serum albumin (HSA) was studied by several techniques. Fluorescence spectroscopy showed an energy transfer between the single tryptophan residue of HSA and the POM. Circular dichroism led to the conclusion that the POM significantly altered the secondary structure of HSA. Isothermal titration calorimetry revealed an enthalpy-driven binding reaction between HSA and the POM, resulting in the formation of a 1:1 complex.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Routine use of Xeomin® in patients previously treated with Botox®: long term resultsEUROPEAN JOURNAL OF NEUROLOGY, Issue 2009D. Dressler Background and purpose:, Based upon large and carefully performed studies Xeomin® was first registered in 2005. However, its real potential can only be assessed, when it is used outside of study design restrictions, in an independent setting, in off-label indications and during continued use. Methods and results:, Two hundred and sixty-three patients (91 with dystonia, 84 with spasticity, 17 with hemifacial spasm and re-innervation synkinesias, 64 with hyperhidrosis, 7 with hypersalivation), who were previously treated with Botox® for at least 1 year under stable conditions, were converted in a blinded fashion to Xeomin® using a 1:1 conversion ratio and identical treatment parameters. Therapeutic outcome and adverse effects were monitored by neurological examination and structuralised interviews. In 223 patients (all except those with axillary hyperhidrosis) Xeomin® was used continuously throughout a 3 year period. Altogether 1050 injection series were performed. Patients with dystonia received 261.5 ± 141.0 MU Botox®/Xeomin®, patients with spasticity 450.5 ± 177.1 MU, patients with hemifacial spasm and reinnervation synkinesias 44.7 ± 19.5 MU and patients with hyperhidrosis 286.9 ± 141.6 MU. The maximum botulinum toxin dose applied was 840 MU. There were no subjective or objective differences between Botox® and Xeomin® treatments with respect to onset latency, maximum and duration of their therapeutic effects and their adverse effect profiles. Long-term use did not reveal additional safety relevant aspects. None of the patients lost therapeutic efficacy during the observation period. Conclusions:, Xeomin® can be used safely in doses of up to 840 MU. Even when applied in high doses it did not produce secondary therapy failure. There were no diffusion differences between Botox® and Xeomin®. Using a conversion ratio of 1:1 Xeomin® and Botox® can easily be exchanged in a continued treatment. [source] One-year follow up of patients with chronic tinnitus treated with left temporoparietal rTMSEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2009E. M. Khedr Background and purpose: Although there are a number of positive reports on the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) for treatment of tinnitus, there are few details about the duration of treatment effects or the relative efficiency of different rTMS protocols. Methods: Sixty six patients with chronic tinnitus were divided into four groups, receiving sham rTMS, 1, 10 and 25 Hz rTMS applied each day for 10 days over left temporoparietal cortex. They were followed up at 4 months and 1 year using the tinnitus questionnaire [Tinnitus Handicap Inventory(THI)] and self ratings of annoyance as well as measures of residual inhibition. Results: A two factor anova revealed a significant ,rTMS' × ,time' interaction indicating that real and sham rTMS had different effects on the THI scale and annoyance of tinnitus (P = 0.026 and 0.046 respectively). After 1 year, the tinnitus was absent in one or both ears of 10 patients who had received real rTMS: one of these was in the 1 Hz group, four patients were in the 10 Hz group and five patients were in the 25 Hz group. Conclusion: Some patients show a lasting benefit at 1 year after 10 days of rTMS treatment. It appears that treatment at 10 or 25 Hz may be more beneficial than at 1 Hz, although more work is necessary to validate this conclusion. [source] Chronic high dose transdermal nicotine in Parkinson's disease: an open trialEUROPEAN JOURNAL OF NEUROLOGY, Issue 12 2007G. Villafane Whether nicotine has therapeutic effects on Parkinson's disease (PD) symptoms is controversial, but high doses and chronic treatment have never been tested. We report the results of a pilot, open-label trial to assess the safety and possible efficacy of chronic high doses of nicotine. Six patients with advanced idiopathic PD received increasing daily doses of transdermal nicotine up to 105 mg/day over 17 weeks. All patients but one accepted the target dose. Nausea and vomiting were frequent but moderate, and occurred in most of the patients (four of six) who received over 90 mg/day and 14 weeks of nicotine treatment. During the plateau phase, patients improved their motor scores and dopaminergic treatment was reduced. These results confirm the feasibility of chronic high dose nicotinic treatment in PD but warrant validation of the beneficial effects by a randomized controlled trial. [source] Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of palmitoylethanolamideEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2008Frida Loría Abstract Cannabinoids have recently been approved as a treatment for pain in multiple sclerosis (MS). Increasing evidence from animal studies suggests that this class of compounds could also prove efficient to fight neurodegeneration, demyelination, inflammation and autoimmune processes occurring in this pathology. However, the use of cannabinoids is limited by their psychoactive effects. In this context, potentiation of the endogenous cannabinoid signalling could represent a substitute to the use of exogenously administrated cannabinoid ligands. Here, we studied the expression of different elements of the endocannabinoid system in a chronic model of MS in mice. We first studied the expression of the two cannabinoid receptors, CB1 and CB2, as well as the putative intracellular cannabinoid receptor peroxisome proliferator-activated receptor-,. We observed an upregulation of CB2, correlated to the production of proinflammatory cytokines, at 60 days after the onset of the MS model. At this time, the levels of the endocannabinoid, 2-arachidonoylglycerol, and of the anti-inflammatory anandamide congener, palmithoylethanolamide, were enhanced, without changes in the levels of anandamide. These changes were not due to differences in the expression of the degradation enzymes, fatty acid amide hydrolase and monoacylglycerol lipase, or of biosynthetic enzymes, diacylglycerol lipase-, and N -acylphosphatidylethanolamine phospholipase-D at this time (60 days). Finally, the exogenous administration of palmitoylethanolamide resulted in a reduction of motor disability in the animals subjected to this model of MS, accompanied by an anti-inflammatory effect. This study overall highlights the potential therapeutic effects of endocannabinoids in MS. [source] Nanofibrous Patches for Spinal Cord RegenerationADVANCED FUNCTIONAL MATERIALS, Issue 9 2010Yiqian Zhu Abstract The difficulty in spinal cord regeneration is related to the inhibitory factors for axon growth and the lack of appropriate axon guidance in the lesion region. Here scaffolds are developed with aligned nanofibers for nerve guidance and drug delivery in the spinal cord. Blended polymers including poly(L -lactic acid) (PLLA) and poly(lactide- co -glycolide) (PLGA) are used to electrospin nanofibrous scaffolds with a two-layer structure: aligned nanofibers in the inner layer and random nanofibers in the outer layer. Rolipram, a small molecule that can enhance cAMP (cyclic adenosine monophosphate) activity in neurons and suppress inflammatory responses, is immobilized onto nanofibers. To test the therapeutic effects of nanofibrous scaffolds, the nanofibrous scaffolds loaded with rolipram are used to bridge the hemisection lesion in 8-week old athymic rats. The scaffolds with rolipram increase axon growth through the scaffolds and in the lesion, promote angiogenesis through the scaffold, and decrease the population of astrocytes and chondroitin sulfate proteoglycans in the lesion. Locomotor scale rating analysis shows that the scaffolds with rolipram significantly improved hindlimb function after 3 weeks. This study demonstrates that nanofibrous scaffolds offer a valuable platform for drug delivery for spinal cord regeneration. [source] Are the therapeutic effects of homoeopathy attributed to the consultation, the homoeopathic remedy, or both?FOCUS ON ALTERNATIVE AND COMPLEMENTARY THERAPIES AN EVIDENCE-BASED APPROACH, Issue 4 2003Protocol for an exploratory randomised controlled trial in rheumatoid arthritis patients [source] Ultrastructural clues for the potent therapeutic effect of melatonin on aging skin in pinealectomized ratsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2006Mukaddes E Abstract Recently we have reported a significant reduction in the thickness of epidermis and epidermis + dermis in the back, abdominal and thoracic skin of the long-term pinealectomized rats and the potent therapeutic effect of melatonin on the pinealectomy-induced morphometric changes. The present study was aimed to determine the fine structure of the abdominal and thoracic skin in pinealectomized rats and the effect of melatonin on skin ultrastructure. Rats were pinealectomized or sham operated (control) for 6 months. Half of the pinealectomized rats were treated with 4 mg/kg melatonin during the last month of the experiment. Pinealectomy resulted in prominent ultrastructural changes in the skin. Epidermal atrophy, disorganization and cytological atypia were obvious. Tonofilament distribution was not uniform, and intercellular space was narrow. Nuclear irregularity and heterochromatin condensation were detected. Many mitochondria were irregular and edematous with increased translucence of the matrix, either partial or total destruction of crests and frequently the presence of vacuoles, myelin figures and dense bodies. Microprojections of basal cells into the dermis were observed. The dermis was thin, and collagenous fibers were loosely arranged. The epidermis in melatonin administered pinealectomized rats was obviously thicker than that of pinealectomized rats. The cells of each layers had characteristic morphological and ultrastructural features. Nuclear irregularity and heterochromatin condensation were not seen. Mitochondria were generally normal in ultrastructural appearance but rarely vacuoles and myelin figures were observed. The dermis was thick, and collagenous fibers were closely packaged. This paper provides an additional ultrastructural evidence that the damage to mitochondria is the major contributory factor to skin aging and that melatonin has potent therapeutic effects in reducing age-related changes via protecting fine structure of the skin. [source] Use of activated protein C has no avail in the early phase of acute pancreatitisHPB, Issue 6 2008Sinan Akay Abstract Objectives. Sepsis and acute pancreatitis have similar pathogenetic mechanisms that have been implicated in the progression of multiple organ failure. Drotrecogin alfa, an analogue of endogenous protein C, reduces mortality in clinical sepsis. Our objective was to evaluate the early therapeutic effects of activated protein C (APC) in a rat model of acute necrotizing pancreatitis. Subjects and method. Acute necrotizing pancreatitis was induced by intraductal injection of 5% Na taurocholate. Hourly bolus injections of saline or recombinant human APC (drotrecogin alfa) was commenced via femoral venous catheter four hours after the induction of acute pancreatitis. The experiment was terminated nine hours after pancratitis induction. Animals in group one (n=20) had a sham operation while animals in group two (n=20) received saline and animals in group three (n=20) received drotrecogin alfa boluses after acute pancreatitis induction. Pancreatic tissue for histopathologic scores and myeloperoxidase, glutathione reductase, glutathione peroxidase, and catalase activites were collected, and blood for serum amylase, urea, creatinine, and inleukin-6 measurements was withdrawn. Results. Serum amylase activity was significantly lower in the APC treated group than the untreated group (17,435±432 U/L vs. 27,426±118 U/L, respectively). While the serum interleukin-6 concentration in the APC untreated group was significantly lower than the treated group (970±323 pg/mL vs. 330±368 pg/mL, respectively). Conclusion. In the early phase of acute pancreatitis, drotrecogin alfa treatment did not result in a significant improvement in oxidative and inflammatory parameters or renal functions. [source] Probiotics and the management of inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 3 2004FRCPC, Richard N. Fedorak MD Abstract The demonstration that immune and epithelial cells can discriminate between different microbial species has extended our understanding of the actions of probiotics beyond simple barrier and antimicrobial concepts. Several probiotic mechanisms of action, relative to inflammatory bowel disease, have been elucidated: (1) competitive exclusion, whereby probiotics compete with microbial pathogens for a limited number of receptors present on the surface epithelium; (2) immunomodulation and/or stimulation of an immune response of gut-associated lymphoid and epithelial cells; (3) antimicrobial activity and suppression of pathogen growth; (4) enhancement of barrier function; and (5) induction of T cell apoptosis in the mucosal immune compartment. The unraveling of these mechanisms of action has led to new support for the use of probiotics in the management of clinical inflammatory bowel disease. Though level 1 evidence now supports the therapeutic use of probiotics in the treatment of postoperative pouchitis, only levels 2 and 3 evidence is currently available in support of the use of probiotics in the treatment of ulcerative colitis and Crohn's disease. Nevertheless, one significant and consistent finding has emerged during the course of research in the past year: not all probiotic bacteria have similar therapeutic effects. Rigorously designed, controlled clinical trials are vital to investigate the unresolved issues related to efficacy, dose, duration of use, single or multi-strain formulation, and the concomitant use of prebiotics, synbiotics, or antibiotics. [source] 99mTc-MIBI imaging for prediction of therapeutic effects of second-generation MDR1 inhibitors in malignant brain tumorsINTERNATIONAL JOURNAL OF CANCER, Issue 12 2007Toshio Sasajima Abstract The aim of this study was to explore whether 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) is suitable to elucidate multidrug resistance and prediction of potentiation of antitumor agents by second-generation MDR1 inhibitors (PSC833, MS-209) in malignant brain tumors in rat. Malignant tumor cells (RG2 and C6 gliomas, Walker 256 carcinoma) were incubated with low dose vincristine (VCR) to induce multidrug resistance. MTT assay demonstrated a significant increase of surviving fractions in VCR-resistant sublines compared to those of drug-naive cells. Reverse transcriptase polymerase chain reaction revealed higher expression of MDR1 mRNA in VCR-resistant cells than drug-naive cells in each line. Volume distribution (Vd) of 99mTc-MIBI was negatively correlated with MDR1 mRNA expression among drug-naive and VCR-resistant cells. MDR1 inhibitors decreased surviving fractions and increased Vd of 99mTc-MIBI significantly in VCR-resistant sublines, whereas MDR1 mRNA expression was unchanged. These findings indicate that 99mTc-MIBI efflux was functionally suppressed by MDR1 inhibitors. Autoradiographic images of 99mTc-MIBI revealed higher uptake in drug-naive cells at basal ganglia compared with VCR-resistant cells at the opposite basal ganglia of rats. Oral administration of the second-generation MDR1 inhibitors significantly increased 99mTc-MIBI accumulation of both tumors. Therapeutic effects of VCR with or without the MDR1 inhibitors were also evaluated autoradiographically using 14C-methyl- L -methionine (14C-Met) and MIB-5 index. 14C-Met uptake and MIB-5 index of both tumors treated with VCR following the MDR1 inhibitor treatment significantly decreased compared with tumors treated with VCR alone. Analysis of 99mTc-MIBI accumulation is considered informative for detecting MDR1-mediated drug resistance and for monitoring the therapeutic effects of MDR1 inhibitors in malignant brain tumors. © 2007 Wiley-Liss, Inc. [source] Dynamic T1-weighted monitoring of vascularization in human carcinoma heterotransplants by magnetic resonance imaging,INTERNATIONAL JOURNAL OF CANCER, Issue 1 2003Fabian Kiessling Abstract Studies on tumor angiogenesis and antiangiogenic therapies are commonly performed with tumor heterotransplants in nude mice. To monitor therapeutic effects, improved noninvasive analyses of functional data are required, in addition to the assessment of tumor volume and histology. Here, we report on sequential monitoring of vascularization of human squamous cell carcinomas growing as heterotransplants in nude mice using MRI. Using a custom-developed animal coil in a conventional whole-body 1.5 T MRI scanner, dynamic T1w sequences were recorded after i.v. injection of Gd-DTPA in tumors grown for 17, 21, 25, 29 and 33 days. Amplitude and the exchange rate constant (kep) were calculated according to a 2-compartment model, discriminating intravascular and interstitial spaces, and correlated with tumor size and histology. High-resolution imaging of small heterotransplants from 100 to 1,000 mm3 was achieved, clearly discriminating vital and necrotic areas. Preceding the development of necroses, which were hyperintense in T2w images and confirmed with histology, a local decrease of amplitude and kep values was observed. Significantly higher amplitudes were found in tumor periphery than in central parts, correlating well with the vascular pattern obtained by immunocytochemistry. Tumor size correlated negatively with amplitude, probably as a result of increasing necrotic areas, whereas the reason for the observed increase of kep value with tumor size remains unclear. These data demonstrate that dynamic MRI is an excellent method for noninvasive assessment of tumor vascularization in small animals using a clinical whole-body scanner with little technical modifications. This technique provides functional data characterizing essential features of tumor biology and is thus appropriate for monitoring antiangiogenic therapies. © 2002 Wiley-Liss, Inc. [source] Basis of occlusive therapy in psoriasis: correcting defects in permeability barrier and calcium gradientINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2001Sang Min Hwang MD Background Although occlusive dressings have great potential in the management of psoriasis vulgaris, the therapeutic mechanism is not completely understood. Occlusion artificially restores and corrects the defective barrier in psoriasis plaques. Additionally, occlusion is know to normalize the epidermal calcium gradients in hyperproliferative murine skin models. Methods To investigate the basis of the therapeutic effect of occlusion on psoriatic plaques, we investigated the ultrastructural morphology of intercorneocyte lipid layers, lamellar bodies, and calcium gradient in chronic plaque-type psoriasis after occlusion with a water vapor-impermeable membrane. The specimens were processed for electron microscopy using: (i) ruthenium tetroxide postfixation; and (ii) ion-capture cytochemistry for calcium localization. Results Occlusion for 7 days resulted in a nearly mature pattern of intercellular multilamellar structures, re-establishment of the near-normal epidermal calcium gradient, and disappearance of calcium precipitates from the stratum corneum interstices. Conclusions The normalization of the permeability barrier and epidermal calcium gradient may play important roles in the therapeutic effects of occlusive dressings in chronic plaque-type psoriasis. [source] Therapeutic effects of long-term administration of an oral adsorbent in patients with chronic renal failure: two-year studyINTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2005NOBUYOSHI TAKAHASHI Abstract Background:, Kremezin is an oral adsorbent that attenuates the progression of chronic renal failure by removing uremic toxins and their precursors from the gastrointestinal tract. Previously two clinical studies based on reciprocal serum creatinine levels (1/Scr) have confirmed the efficacy of Kremezin (Kureha Chemical, Tokyo, Japan) in undialyzed patients who had been followed up for 6 months or 1 year. This is the first report to evaluate the therapeutic effects of long-term administration (2 years.) of Kremezin in undialyzed patients. Methods:, Kremezin was given to 48 enrolled undialyzed patients with a median Scr level of 4.3 mg/dL. Rates of decline of 1/Scr, as well as the time for Scr level to reach 10 mg/dL, the critical value requiring dialysis, were compared before and after administration of Kremezin. Results:, During the 2-year therapeutic period, 1/Scr gradients were significantly attenuated (P = 0.0083), and the estimated time to dialysis was prolonged from 16.3 ± 16.3 months to 29.8 ± 24.1 months (P = 0.002). When the patients were divided into two groups, based on of systolic blood pressure (SBP), defined by the World Health Organization (WHO) classification, a significantly smaller number of patients in the low blood pressure group (SBP < 160 mmHg) were introduced to dialysis (P = 0.0005), and the estimated time to dialysis was significantly extended in the low blood pressure group (P = 0.0125). Conclusion:, In addition to the control of blood pressure in undialyzed patients, Kremezin has additive salutary effects to halt the progressive loss of renal function, resulting in the delay of dialysis. [source] Electroconvulsive Therapy and the Fear of DevianceJOURNAL FOR THE THEORY OF SOCIAL BEHAVIOUR, Issue 1 2002James Giles After reaching the verge of obsolescence, electroconvulsive therapy (ECT) is once again on the increase. There remains, however, no sound theoretical basis for its use. By 1948 at least 50 different theories had been proposed to account for the workings of ECT. Today there are numerous more. Further, there is no good evidence for its therapeutic effectiveness. Although some studies show what are claimed to be positive results, others show significant amount of relapse, even with severe depression (the disorder against which ECT is supposed to be most effective), while even other studies show ECT to have little more effect than a placebo. Finally, there is much evidence for ECTs damaging effects, particularly to cognitive functioning like memory, general intelligence level, and perceptual abilities, and quite possibly to brain functioning. Some studies even suggest that the alleged therapeutic effects of ECT are essentially the effects of organic brain damage. The question, then, is why, despite these problems, does ECT continue to be used? ECTs salient features suggest an answer here. These are the features of dehumanization, power, control, punishment, and others, all of which can be traced back to the fear of deviant psychotic behavior. [source] Effects of Four Therapy Procedures on Communication in People with Profound Intellectual DisabilitiesJOURNAL OF APPLIED RESEARCH IN INTELLECTUAL DISABILITIES, Issue 2 2001William R. Lindsay A number of alternative therapies have recently been employed with people who have intellectual disabilities (IDs). The present study examines the effects of four frequently used therapies on the communication of people with profound ID. Communication was assessed using five measures of positive communication and five measures of negative communication. The therapies assessed were Snoezelen, active therapy, relaxation and aromatherapy/hand massage. There were eight participants in the present study and each received all four of the therapeutic procedures in a counterbalanced design. Treatment procedures were videotaped at sessions 5, 10, 15 and 20, and later scored for defined measures of communication. Both Snoezelen and relaxation increased the level of positive communication and had some effect on decreasing negative communication. However, active therapy and aromatherapy/hand massage had little or no effect on communication. The lack of a no-treatment control is noted, especially in the light of trends seen at baseline. Considering the lack of generalization of therapeutic effects, the present results should be treated with caution. [source] | ||||||||||||||||||||||||||||||||||||||||