Alleviation of pain in painful diabetic neuropathy

Introduction: Painful diabetic neuropathy (PDN) is a disabling pain condition. Its pathomechanism remains unknown, but a sensitization and neuronal hyperexcitabilty have been suggested. Only symptomatic pharmacological pain management treatment is currently available.

Areas covered: The origin of PDN is enigmatic, and the evidence-based therapeutic guidelines therefore consist only of antidepressants and antiepileptics as first-line recommended drugs. This article relates to a MEDLINE/PubMed systematic search (2005-2015).

Expert opinion: The results of the meta-analysis from the aspect of the efficacy of amitriptyline, duloxetine, venlafaxine, gabapentin and pregabalin are favorable, but the placebo response rate is relatively high in patients with neuropathic pain. For personalization of the medication of PDN patients, the optimum dosing, the genotyping of the metabolizing enzymes and optimum biomarkers are needed. As concerns the future perspectives, specific sodium channel subtype inhibitors acting on peripheral nociceptive neurons or modified T-type voltage-gated calcium channel blockers may be promising targets for pharmaceutical innovations. Another attractive strategy for the treatment is based on the effects of monoclonal antibodies against nerve growth factor, sodium channels, specific receptor and cytokines. Botulinum toxin A, capsaicin patch and spinal cord stimulation therapies are the nearest future therapeutic options for the treatment of PDN patients.     

Alleviation of Nickel-Induced Biochemical Alterations by Chelating Agents

Alleviation of Nickel-Induced Biochemical Alterations by ChelatingAgents. Misra, M., Athar, M., Hasan, S. K., and Srivastava,R. C. (1988). Fundam. Appl. Toxicol 11, 285–292. The effectof 1,4,8,11-tetraazacyclotetradecane (Cyclam), triethylenetetramine(TETA), reduced glutathione (GSH), ethylenediamine tetraaceticacid (EDTA), cyclohexanediamine tet-raacetic acid (CDTA), diethylenetriamine pentaacetic acid (DTPA), and hydroxyethylenedia-minetriacetic acid (HEDTA) on the alleviation of nickel-inducedbiochemical and trace-metal alterations in serum, liver, andkidney of nickel-treated rats was studied. The lipophilic chelatingagents Cyclam and TETA exhibited a higher order of effectivenessin alleviating nickel-induced alterations compared to EDTA,CDTA, DTPA, and HEDTA, the hydrophilic chelating agents. Thehigher efficacy of lipophilic agents may be due to their abilityto bind to nickel present in extracellular fluid as well asin intracellular fluid, while the hydrophilic agents may bindonly to nickel present in extracellular fluid. Our data alsosuggest that the efficacy of Cyclam to ameliorate nickel-inducedalterations is exceptionally high.     

Alleviation of prilocaine-induced epileptiform activity and cardiotoxicity by thymoquinone

PurposeThis study investigated whether thymoquinone (TQ) could alleviate central nervous system (CNS) and cardiovascular toxicity of prilocaine, a commonly used local anesthetic.MethodsRats were randomized to the following groups: control, prilocaine treated, TQ treated and prilocaine + TQ treated. Electroencephalography and electrocardiography electrodes were placed and trachea was intubated. Mechanical ventilation was initiated, right femoral artery was cannulated for continuous blood pressure measurements and blood-gas sampling while the left femoral vein was cannulated for prilocaine infusion. Markers of myocardial injury, reactive oxygen/nitrogen species (ROS/RNS) generation and total antioxidant capacity (TAC) were assayed by standard kits. Aquaporin-4 (AQP4), nuclear factor(NF)κB-p65 and -p50 subunit in brain tissue were evaluated by histological scoring.ResultsBlood pH and partial oxygen pressure, was significantly decreased after prilocaine infusion. The decrease in blood pH was alleviated in the prilocaine + TQ treated group. Prilocaine produced seizure activity, cardiac arrhythmia and asystole at significantly lower doses compared to prilocaine + TQ treated rats. Thymoquinone administration attenuated levels of myocardial injury induced by prilocaine. Prilocaine treatment caused increased ROS/RNS formation and decreased TAC in heart and brain tissue. Thymoquinone increased heart and brain TAC and decreased ROS/RNS formation in prilocaine treated rats. AQP4, NFκB-p65 and NFκB-p50 expressions were increased in cerebellum, cerebral cortex, choroid plexus and thalamic nucleus in prilocaine treated rats. Thymoquinone, decreased the expression of AQP4, NFκB-p65 and NFκB-p50 in brain tissue in prilocaine + TQ treated rats.ConclusionResults indicate that TQ could ameliorate prilocaine-induced CNS and cardiovascular toxicity.Graphical abstract     

Alleviation of anisomycin-induced amnesia by pre-test treatment with lysine-vasopressin

Amnesia in mice for a passive avoidance response induced by anisomycin injection immediately after training was reversed by 40 micrograms of lysine-vasopressin given one hour before testing. Control groups receiving non-contingent shock instead of training were used to demonstrate that the effects of vasopressin were due to memory of shock received in a particular place, rather than non-specific suppression of locomotion. The effects of vasopressin on retention were not mimicked by either pentylenetetrazol or epinephrine suggesting that the enhanced latencies were probably not the result of increases in fear or arousal. These data support the hypothesis that the retrieval of memory can be facilitated by vasopressin. The possibility of a relationship between the effects of vasopressin and those of catecholamine manipulations on memory is discussed.     

Alleviation of scopolamine amnesia by different retrieval enhancing treatments

Mice were trained in a one-way active avoidance task to a criterion of 9/10 avoidances. Immediately following training they were injected with scopolamine hydrochloride (1 mg/kg SC) or with saline. Retention was assessed 3 days after training by 5 test trials on which the UCS was not present. Thirty min prior to the test, groups were injected with different doses of arecoline, d-amphetamine sulphate or with saline. Other scopolamine-treated mice were exposed to the CS or the UCS 24 hr prior to the test. The scopolamine-induced amnesia was attenuated by both 0.5 and 1.0 mg/kg arecoline and by 2.0 mg/kg d-amphetamine. Retention was also improved by exposure to the CS and the UCS. These data show that scopolamine amnesia can be alleviated by treatments which activate retrieval processes.     

不同吸痰方法对喉癌气管切开患者气道内吸痰舒适度的影响

目的观察两种不同吸痰方法对喉癌气管切开患者气道内吸痰舒适度的影响。方法将19例气管切开术后患者随机分为观察组(10例)和对照组(9例),分别采用试验吸痰法(观察组)和常规吸痰法(对照组)吸痰各10d,对两种吸痰方法吸痰效果、患者心理接受程度,舒适度进行对比研究。结果两种吸痰方法的吸痰效果无明显差异,但观察组患者的心理接受程度及舒适度评分均高于对照组,两组比较有显著差异性(t=0.12相似文献   

Alleviation of doxorubicin-induced nephrotoxicity and hepatotoxicity by chrysin in Wistar rats

Abstract

Objective: Doxorubicin (DXR) is an anticancer drug used in the treatment of many human malignancies. However, its clinical use is limited because of several side effects like cardiotoxicity, nephrotoxicity and hepatotoxicity. In the present study, we investigated the protective efficacy of chrysin against DXR-induced oxidative stress, nephro- and hepatotoxicity in male Wistar rats using biochemical and histopathological approaches.

Methodology: Wistar rats were subjected to concomitant pre- and post-phylactic oral treatment of chrysin (40 and 80?mg/kg b.wt.) against nephro- and hepatotoxicity induced by single i.p. injection of DXR (40?mg/kg b.wt). Nephrotoxicity and hepatotoxicity were assessed by measuring the level of serum creatinine, BUN, AST, ALT and LDH. The level of antioxidant armory of kidney and liver tissue was also measured.

Key findings: Treatment with chrysin significantly decreased the levels of serum toxicity markers and additionally elevated antioxidant defense enzyme levels. Histopathological changes further confirmed the biochemical results showing that DXR caused significant structural damage to kidney and liver tissue architecture which were reversed with chrysin.

Conclusion: The results suggest that chrysin attenuated nephro and hepatic damage induced by DXR.     

Memory retrieval deficits: Alleviation by etiracetam,a nootropic drug

Etiracetam, a nonanaleptic drug related to the nootropic substance piracetam, was found to facilitate memory retrieval in rats in several experimental situations, when injected 30 min prior to retention testing. The drug was active when memory deficits were induced by electroconvulsive shock, undertraining, or by a long training-to-test interval. The behavioral paradigms included a one-trial inhibitory avoidance task and a complex multitrial, spatially discriminated approach task. The clinical interest of drugs which facilitate retrieval processes is also discussed.These results were reported, in part, at the Conference on Practical Aspects of Memory, Cardiff, 1978     

1例残肢痛伴幻肢痛药物治疗方案分析

目的 探讨药学监护在1例残肢痛伴幻肢痛药物治疗过程中的作用。方法 对患者治疗方案运用循证药学的思维进行讨论,并对该患者具体用药进行分析。结果 采用卡马西平、非甾体抗炎药用于幻肢痛治疗不合理。结论 循证药学临床思维在患者用药治疗过程中可以发挥重要作用,有助于提高临床药师的药学服务水平,促进合理用药。     

Alleviation of cyclosporin-induced immune suppression by the cytokine inducer ADA-202-718

ADA-202-718 (ADA) has been shown to augment the production of various cytokines (IL-1, IL-2 and gamma-interferon) by murine T lymphocytes. Administration of 1 mg/kg/day to mice from the time of immunization significantly enhanced delayed-type hypersensitivity responses to sheep red blood cells (SRBC). ADA also inhibited immune suppression in mice given 25 but not 50 mg/kg/day cyclosporin A (CsA). There were, however, few changes compared with vehicle-treated controls in the numbers of splenic regulatory T cell subsets (L3T4+ and Ly2+) following treatment with CsA, ADA or both drugs. On the other hand, splenic lymphocytes from ADA-treated animals exhibited augmented proliferative responses to polyclonal T and B cell mitogens and antigen. ADA (1 mg/kg) also stimulated the splenic IgM plaque-forming cell response to SRBC and prevented CsA (25 mg/kg)-induced suppression of humoral immunity. In vitro, ADA (2 micrograms/ml) inhibited CsA-induced suppression of T cell proliferation, the effect being most marked at lower inhibitory concentrations of CsA. These data illustrate the capacity of ADA to augment or restore T cell responses in experimental animals and are consistent with the view that CsA acts in these experimental in vivo systems by inhibition of cytokine production.