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Useful Agents (useful + agent)
Selected AbstractsEffects of dexmedetomidine on intraoperative motor and somatosensory evoked potential monitoring during spinal surgery in adolescentsPEDIATRIC ANESTHESIA, Issue 11 2008JOSEPH D. TOBIAS MD Summary Background:, Dexmedetomidine may be a useful agent as an adjunct to an opioid,propofol total intravenous anesthesia (TIVA) technique during posterior spinal fusion (PSF) surgery. There are limited data regarding its effects on somatosensory (SSEPs) and motor evoked potentials (MEPs). Methods:, The data presented represent a retrospective review of prospectively collected quality assurance data. When the decision was made to incorporate dexmedetomidine into the anesthetic regimen for intraoperative care of patients undergoing PSF, a prospective evaluation of its effects on SSEPs and MEPs was undertaken. SSEPs and MEPs were measured before and after the administration of dexmedetomidine in a cohort of pediatric patients undergoing PSF. Dexmedetomidine (1 ,g·kg,1 over 20 min followed by an infusion of 0.5 ,g·kg,1·h,1) was administered at the completion of the surgical procedure, but prior to wound closure as an adjunct to TIVA which included propofol and remifentanil, adjusted to maintain a constant depth of anesthesia as measured by a BIS of 45,60. Results:, The cohort for the study included nine patients, ranging in age from 12 to 17 years, anesthetized with remifentanil and propofol. In the first patient, dexmedetomidine was administered in conjunction with propofol at 110 ,g·kg,1·min,1 which resulted in a decrease in the bispectral index from 58 to 31. Although no significant effect was noted on the SSEPs (amplitude or latency) or the MEP duration, there was a decrease in the MEP amplitude. The protocol was modified so that the propofol infusion was incrementally decreased during the dexmedetomidine infusion to achieve the same depth of anesthesia. In the remaining eight patients, the bispectral index was 52 ± 6 at the start of the dexmedetomidine loading dose and 49 ± 4 at its completion (P = NS). There was no statistically significant difference in the MEPs and SSEPs obtained before and at completion of the dexmedetomidine loading dose. Conclusion:, Using the above-mentioned protocol, dexmedetomidine can be used as a component of TIVA during PSF without affecting neurophysiological monitoring. [source] Prophylaxis effect of Trigonella foenum graecum L. seeds on renal stone formation in ratsPHYTOTHERAPY RESEARCH, Issue 10 2007Amine Laroubi Abstract Despite considerable progress in medical therapy, there is no satisfactory drug to treat kidney stones. Therefore, the current study aimed to look for an alternative by using Trigonella foenum graecum (Tfg) on nephrolithiasic rats as a preventive agent against the development of kidney stones, which is commonly used in Morocco as a phytotherapeutic agent. The inhibitory effect of the aqueous extract of Tfg seeds was examined on the formation of calcium oxalate renal stones induced by ethylene glycol (EG) with ammonium chloride. At the end of the experiment all kidneys were removed and examined microscopically for possible crystal/stone locations and the total calcium amount in the renal tissue was evaluated. The blood was recovered to determine the levels of calcium, phosphorus, creatinine and urea. The results showed that the amount of calcification in the kidneys and the total calcium amount of the renal tissue in rats treated with Tfg were significantly reduced compared with the untreated group. Consequently, Tfg may be a useful agent in the treatment of patients with calcic urolithiasis. Copyright © 2007 John Wiley & Sons, Ltd. [source] Puerarin Inhibits C-Reactive Protein Expression via Suppression of Nuclear Factor ,B Activation in Lipopolysaccharide-Induced Peripheral Blood Mononuclear Cells of Patients with Stable Angina PectorisBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2010Xiangjun Yang In this report, we examined the ability of puerarin to modulate C-reactive protein (CRP) expression and key molecules in the nuclear factor kappa B (NF-,B) pathway to determine its molecular target. The protein and mRNA levels of CRP were determined in lipopolysaccharide (LPS)-induced peripheral blood mononuclear cells of patients with unstable angina pectoris. Also, we detected the I-,B, phosphorylation and the p65NF-,B expression in peripheral blood mononuclear cells under our experimental condition. The results indicated that puerarin inhibited the expression of the protein and mRNA levels of CRP in LPS-induced peripheral blood mononuclear cells. Subsequently, we determined that the inhibition of CRP expression was because of a dose-dependent inhibition of phosphorylation and degradation of inhibitor kappaB(I-,B), which resulted in a reduction of p65NF-,B nuclear translocation. We conclude that puerarin acts as an anti-inflammatory agent by blocking NF-,B signalling, and may possibly be developed as a useful agent for the chemoprevention of atherosclerosis. [source] Either interleukin-12 or interferon-, can correct the dendritic cell defect induced by transforming growth factor ,1 in patients with myelomaBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2004Ross Brown Summary The poor response to immunotherapy in patients with multiple myeloma (MM) indicates that a better understanding of any defects in the immune response in these patients is required before effective therapeutic strategies can be developed. Recently we reported that high potency (CMRF44+) dendritic cells (DC) in the peripheral blood of patients with MM failed to significantly up-regulate the expression of the B7 co-stimulatory molecules, CD80 and CD86, in response to an appropriate signal from soluble trimeric human CD40 ligand. This defect was caused by transforming growth factor ,1 (TGF,1) and interleukin (IL)-10, produced by malignant plasma cells, and the defect was neutralized in vitro with anti-TGF,1. As this defect could impact on immunotherapeutic strategies and may be a major cause of the failure of recent trials, it was important to identify a more clinically useful agent that could correct the defect in vivo. In this study of 59 MM patients, the relative and absolute numbers of blood DC were only significantly decreased in patients with stage III disease and CD80 up-regulation was reduced in both stage I and stage III. It was demonstrated that both IL-12 and interferon- , neutralized the failure to stimulate CD80 up-regulation by huCD40LT in vitro. IL-12 did not cause a change in the distribution of DC subsets that were predominantly myeloid (CD11c+ and CDw123,) suggesting that there would be a predominantly T-helper cell type response. The addition of IL-12 or interferon- , to future immunotherapy trials involving these patients should be considered. [source] Role of valproate across the ages.ACTA NEUROLOGICA SCANDINAVICA, Issue 2006Treatment of epilepsy in children In June 2005 a team of experts participated in a workshop with the objective of reaching agreement on the place of valproate use in the treatment of paediatric epilepsy patients. A general ,consensus of the meeting' was that the initiation of antiepileptic drug (AED) treatment should be based on a seizure-syndromic approach in children. Participants of the meeting also agreed that valproate is currently the AED with the broadest spectrum across all types of seizures and syndromes. Its superiority has been shown over almost 40 years of clinical experience. The best results are seen in idiopathic generalized epilepsy with or without photosensitivity, idiopathic focal and symptomatic generalized tonic,clonic seizures (GTCS). Evidence supports the use of valproate, ethosuximide and lamotrigine in absence epilepsies and the use of carbamazepine, lamotrigine, oxcarbazepine, phenytoin, topiramate, valproate and phenobarbital for primary GTCS. For new AEDs trials have been undertaken to define their therapeutic role but studies comparing their role to ,old' broad-spectrum drugs in specific syndromes are missing. Experts concluded that intravenous (i.v.) valproate is a useful agent in the treatment of non-convulsive status epilepticus (SE). There is an easy transition to oral treatment following i.v. valproate use. The discussion also concluded that, despite the lack of studies, valproate is an interesting, underutilized alternative in convulsive SE but more controlled studies are needed. The side effects of valproate use are well documented. Its effect on cognition and behaviour is more favourable than many of the other AEDs which is an important consideration in children. Overall, the clinical consensus of the meeting was that valproate's well established therapeutic properties far outweigh the negative side effects. Contraindication or withdrawal should be assessed individually. [source] Densiron intraocular tamponade: a case seriesCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 3 2008Beng Liam Lim MBBS(Hons) MPH Abstract Purpose:, To report on the use of Densiron (heavy silicone oil), a new endotamponade agent with proposed benefits in complex retinal detachments involving inferior proliferative vitreoretinopathy. Method:, Retrospective case note review. Results:, Ten cases (10 eyes) in which Densiron was used in eyes which had failed initial retinal detachment surgery. The overall success rate of long-term total reattachment was 70%. Mean preoperative visual acuity was logMAR 2.03 (SD 0.406), which improved to a mean postoperative visual acuity of logMAR 1.00 (SD 0.571) (P = 0.001). Conclusion:, Densiron was well tolerated with few side-effects and appears to be a useful agent in patients with inferior proliferative vitreoretinopathy. [source] Pharmacologic and Therapeutic Considerations in Hypertension Therapy With Calcium Channel Blockers: Focus on VerapamilJOURNAL OF CLINICAL HYPERTENSION, Issue 2 2007Domenic A. Sica MD In the past 2 decades, calcium channel blockers have emerged as important and useful agents for treating hypertension. The safety of this drug class has been vigorously debated for some time, and it has only been in the past few years that such debate has been quieted by favorable outcomes data with these compounds. Calcium channel blockers are a heterogeneous group of compounds as alike as they are dissimilar. Calcium channel blockers can be separated into dihydropyridine and nondihydropyridine subclasses, with representatives of the latter being verapamil and diltiazem. A lengthy treatment experience exists for verapamil, a compound that has progressed from an immediate-release to a sustained-release and, more recently, a delayed/sustained-release formulation designated for administration at bedtime. This latter formulation synchronizes drug delivery with the early morning rise in blood pressure, which is a particularly attractive feature when viewed in the context of the distinctive pharmacokinetic and pharmacodynamic features of verapamil. [source] Sense-making of employment: on whether and why people read employment advertisingJOURNAL OF ORGANIZATIONAL BEHAVIOR, Issue 6 2006Anat Rafaeli This paper suggests a process of sense-making of "employment" and identifies employment ads to be useful agents in this process. It is suggested that individuals read ads in surveillance of the employment market in addition to reading them to search for employment vacancies. Employment ads are suggested to be a forum for organizational self-presentation that offers current information about the employment exchange as it is viewed by employers. Two exploratory studies are presented to support the thesis. Study 1 is an inductive survey of people's reading of employment ads, showing that people read ads even if they are not looking for a job because they view ads as a source of insight about the employment environment. Study 2 reviews the content of employment ads, showing them to convey prevailing elements of the idea of employment, namely that employment is an exchange of employee skills and responsibilities for organizational intrinsic and extrinsic rewards. Recognizing the individual need for sense-making of employment, and identifying employment ads as a source of information about employment, opens up a new area for research and practice on recruiting, organizational self-presentation, and sense-making. Copyright © 2006 John Wiley & Sons, Ltd. [source] Signal transduction pathways involved in the stimulation of tissue type plasminogen activator by interleukin-1, and Porphyromonas gingivalis in human osteosarcoma cellsJOURNAL OF PERIODONTAL RESEARCH, Issue 5 2006Yu-Chao Chang Background:, Recently, evidences have shown that tissue type plasminogen activator (t-PA) may play an important role in the pathogenesis of periodontal diseases. However, the mechanisms and signal transduction pathways involved in the production of t-PA in human osteosarcoma cells are not fully understood. Objectives:, The purpose of this study was to investigate the caseinolytic activity in human osteosarcoma cell line U2OS cells stimulated with interleukin-1, (IL-1,) or Porphyromonas gingivalis in the absence or presence of p38 inhibitor SB203580, mitogen-activated protein kinase kinase (MEK) inhibitor U0126, and phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. Methods:, IL-1, and the supernatants of P. gingivalis were used to evaluate the caseinolytic activity in U2OS cells by using casein zymography and enzyme-linked immunosorbent assay (ELISA). Furthermore, to search possible signal transduction pathways, SB203580, U0126, and LY294002 were added to test how they modulated the caseinolytic activity. Results:, Casein zymography exhibited a caseinolytic band with a molecular weight of approximately 70 kDa, suggestive of the presence of t-PA. Secretion of t-PA was found to be stimulated with IL-1, and P. gingivalis during a 2-day culture period (p < 0.05). From the results of casein zymography and ELISA, SB203580, U0126, and LY294002 significantly reduced the IL-1, or P. gingivalis -stimulated t-PA production, respectively (p < 0.05). Conclusions:, Our findings demonstrated that IL-1, and P. gingivalis enhance t-PA production in human osteosarcoma cells, and that the signal transduction pathways p38, MEK, and PI3K are involved in the inhibition of t-PA. SB203580, U0126, and LY294002 suppress t-PA production and/or activity and may therefore be valuable therapeutics in t-PA-mediated periodontal destruction, and might be proved clinically useful agents, in combination with standard treatment modalities, in the treatment of periodontitis. [source] A new generation of monoclonal and recombinant antibodies against cell-adherent prostate specific membrane antigen for diagnostic and therapeutic targeting of prostate cancerTHE PROSTATE, Issue 13 2006Ursula Elsässer-Beile Abstract BACKGROUND Prostate-specific membrane antigen (PSMA) is an excellent candidate for targeting prostate cancer by virtue of its restricted expression on prostatic epithelial cells and its upregulation on prostatic carcinoma cells. PSMA is expressed on the cell surface displaying a specific three-dimensional structure. Therefore, only antibodies with a high cell binding activity will have an important impact on antibody-based imaging and therapy. METHODS Monoclonal antibodies (mAbs) and single chain antibody fragments (scFvs) were prepared from spleen cells of mice that had been immunized either with purified PSMA or a cell lysate of prostate cancer LNCaP cells containing native PSMA. mAbs and scFvs were screened for reactivity with purified PSMA and binding to PSMA-expressing LNCaP cells. RESULTS From mice immunized with purified PSMA, we obtained three mAbs (K7, K12, D20) and four scFvs (G0, G1, G2, G4), which were highly reactive with the isolated antigen, but showed weak or no reaction with viable LNCaP cells. From mice immunized with unpurified LNCaP lysate, we obtained three mAbs (3/E7, 3/F11, 3/A12), and one scFv (A5), which were reactive with purified PSMA, also showing a strong and specific binding to viable LNCaP cells and PSMA-transfected cells. CONCLUSIONS Our results suggest that only the mAbs and scFvs, that were elicited with unpurified LNCaP lysate and not with purified PSMA will be useful agents for diagnostic imaging and therapeutic applications of prostate cancer. Prostate 66: 1359,1370, 2006. © 2006 Wiley-Liss, Inc. [source] Safety and efficacy of vardenafil versus sertraline in the treatment of premature ejaculation: a randomised, prospective and crossover studyANDROLOGIA, Issue 3 2009M. J. Mathers Summary We investigated safety and efficacy of vardenafil and sertraline in premature ejaculation (PE). Seventy-two men graded their primary PE on a scale of 0,8 (0 = almost never, 8 = almost always). Intravaginal ejaculatory latency time (IELT) was measured. Patients were included if they scored their PE as 4 or greater and their IELTs were less than 1.30 min. After 6 weeks of behavioural psychosexual therapy, 49 patients still had a PE of 4 or greater and an IELT less than 1.30 min and they were randomised: 6 weeks vardenafil (10 mg) or sertraline (50 mg). After a wash-out phase for 1 week, medication was changed in a cross-over design. Initially, all 72 men with PE received behavioural therapy. Twenty-three men were satisfied with treatment and excluded. The remaining 49 men graded their PE as 5.94 ± 1.6 and IELT was 0.59 min and patients were randomised. Four men discontinued the study. Vardenafil improved PE grading: 2.7 ± 2.1 (P < 0.01) and IELT increased to 5.01 ± 3.69 (P < 0.001). PE grading improved 1.92 ± 1.32, (P < 0.01) and IELT 3.12 ± 1.89 (P < 0.001) with sertraline. It is concluded that vardenafil and sertraline are useful agents in the pharmacological treatment of PE. [source] Prolonging androgen sensitivity in prostate cancer , a role for COX inhibitors?ANZ JOURNAL OF SURGERY, Issue 9 2009Andrew Richards Abstract Background:, Advanced prostate cancer has long been known to respond to androgen deprivation, but disease inevitably progresses to become androgen independent. Lengthening the responsive period is an important, yet underinvestigated, clinical goal. This study aims to determine whether cyclooxygenase-2 (COX-2) inhibitors are potentially useful agents in prolonging androgen sensitivity. Methods:, The expression of COX-2 in human prostate surgical specimens, both benign and malignant, androgen dependent and independent, was determined by immunohistochemistry. Nude mice, in which prostate cancer xenografts had been established, were castrated and randomized to receive either COX-2 inhibitor or vehicle for 8 weeks. Time to androgen independence (AIPC), growth rate and rate of PSA rise were compared between groups. COX-2 expression, at the mRNA and protein level, was determined in the native xenograft cell line and in tissues of varying androgen sensitivity derived from the xenografts. Results:, In human tissues, COX-2 protein was expressed in prostate epithelium and was upregulated in prostate cancer and remained upregulated after androgen ablation and in the androgen-independent state. Tissue obtained from the LNCaP xenograft model showed variable COX-2 expression, with some evidence of downregulation in AIPC. The addition of a COX-2 inhibitor to castration does not lengthen the time to AIPC (P= 0.53), rate of tumour growth (P= 0.59) or rate of PSA rise (P= 0.34) in the LNCaP xenograft model. Conclusion:, This study does not support a role for COX-2 inhibitors in prolonging androgen responsiveness in prostate cancer. [source] Attenuation of acute and chronic effects of morphine by the imidazoline receptor ligand 2-(2-benzofuranyl)-2-imidazoline in rat locus coeruleus neuronsBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2003Eduardo Ruiz-Durántez The aim of this study was to determine if 2-(2-benzofuranyl)-2-imidazoline (2-BFI) interacts with the opioid system in the rat locus coeruleus, using single-unit extracellular recordings. In morphine-dependent rats, acute administration of the selective imidazoline receptor ligands 2-BFI (10 and 40 mg kg,1, i.p. and 100 ,g, i.c.v.) or valldemossine (10 mg kg,1, i.p.) did not modify the naloxone-induced hyperactivity of locus coeruleus neurons compared with that observed in the morphine-dependent control group. After chronic administration of 2-BFI (10 mg kg,1, i.p., three times daily, for 5 days) and morphine, naloxone-induced hyperactivity and tolerance to morphine were attenuated. This effect was not observed when a lower dose of 2-BFI (1 mg kg,1, i.p.) or valldemossine (10 mg kg,1, i.p.) were used. Acute administration of 2-BFI (10 and 40 mg kg,1, i.p. and 100 ,g, i.c.v.) but not valldemossine (40 mg kg,1, i.p.) diminished the potency of morphine to inhibit locus coeruleus neuron activity in vivo (ED50 values increased by 2.3, 2.9; and 3.1 fold respectively). Similarly, the potency of Met5 -enkephalin to inhibit locus coeruleus neurons was decreased when 2-BFI (100 ,M) was applied to rat brain slices (EC50 increased by 5.6; P<0.05). The present data demonstrate that there is an interaction between 2-BFI and the opioid system in the locus coeruleus. This interaction leads to an attenuation of both the hyperactivity of locus coeruleus neurons during opiate withdrawal and the development of tolerance to morphine when 2-BFI is chronically administered. These results suggest that imidazoline drugs may prove to be useful agents for the management of opioid dependence and tolerance. British Journal of Pharmacology (2003) 138, 494,500. doi:10.1038/sj.bjp.0705052 [source] | ||||||||||