ABSTRACT
Wake-Promoting Agents [WPAs] such as amphetamine-like stimulants or modafinil, armodafinil, methyl phenidate, caffeine and nicotine reinforce the level of vigilance through an stimulated release of neurotransmitters implicated in the arousal threshold maintenance, hence shift the drive from the sleep-promoting to wake-promoting system. The modulatory effects of WPAs on cortical activation pathways give rise to enhanced vigilance. For example, cholinergic neurons of the basal forebrain and the adenosine receptors on these neurons are agonized and antagonized by nicotine and caffeine, respectively. Caffeine similarly antagonizes adenosine receptors on the GABAergic neurons and intensifies the inhibitory drive in preoptic/anterior hypothalamus which involve in sleep induction. Modafinil however exerts its wake-promoting effects through stimulating the tuberomammillary nucleus and the hypocretinergic neurons which activate the ascending reticular activating system. Although many neutransmitter systems such as dopamine are thought to be involved upon the effects of WPAs, the empirical evidence to explain the exact mechanisms need to gain strength
ABSTRACT
The present study investigated the possible involvement of the nucleus accumbens' [NAc] nitric oxide system in nicotine's reversal effect upon ethanol-induced amnesia. The hypothesis was tested through ethanol state-dependent memory assessment in adult male Wistar rats. Bilateral chronic cannulae were implanted in the NAc and the animals were trained in a step-through type inhibitory avoidance memory task. The step-through latency was examined 24 h after animals' training. The pre-training or pre-test intraperitoneal [i.p.] injection of ethanol [0.9 g/kg] decreased the step-through latency, indicating an amnesic effect of the drug. Meanwhile, the pre-test administration of ethanol [0.6 and 0.9 g/kg] could reverse the pre-training ethanol [0.9 g/kg]-induced amnesia, suggesting a state-dependent effect. Similar to ethanol, the pre-test intra-NAc microinjection of nicotine [0.25 and 0.5 microg/rat] alone or nicotine [0.1, 0.25 and 0.5 microg/mouse, intra-NAc] in combination with an ineffective dose of ethanol [0.3 g/kg] could significantly reverse the [pre-training] ethanol-induced memory impairment. The ethanol [0.9 g/kg]-induced amnesia was similarly prevented following the pre-test intra-NAc administration of a nitric oxide synthase [NOS] inhibitor, L-NAME [0.4 and 0.8 microg/rat]. Of note, the co-administration of L-NAME [0.04 and 0.08 microg/rat, intra-NAc] with an ineffective dose of nicotine [0.1 micro g/rat, intra- NAc] could significantly potentiate the memory-improving effect of nicotine on ethanol-induced amnesia and resembled the effects of pre-test administration of a higher dose of nicotine. Furthermore, while the pre-test intra-NAc injection of L-NAME impaired the memory retrieval by itself, the pre-test intra-NAc administration of L-arginine, a nitric oxide precursor [0.3 and 0.6 micro g/rat, intra-NAc], did not exert any effect either alone or in combination with an effective dose of nicotine [0.5 micro g/rat, intra-NAc] on pre-training ethanol-induced memory impairment. Our findings indicated a possible role of the nucleus accumbens' nitric oxide system in the improving effects of nicotine on ethanol-induced amnesia and the related state-dependent learning
ABSTRACT
Our knowledge about subjective tinnitus physiopathology has improved in the last decades, while information to understand the main mechanisms that transform a neutral phantom sound to tinnitus distress appear to be inadequate. The current review presents evidence from several studies using neuroimaging, electrophysiology and brain lesion techniques aiming at hypothesizing a new realistic multimodality tinnitus framework which can better explain the structural and functional brain connectivity in different stages of tinnitus development. Further to the present work, a full review of the entire literature should be prompted to discuss evidence to more comprehensively investigate the relationship between structural and functional connectivity of tinnitus. Progresses in such framework will shed lights to the tinnitus neurofunctional model and further evidence-based treatment modalities
ABSTRACT
Given the unmet needs in cancer treatment, extensive research and development has evolved to offer therapies for cancers to extend survival and minimize side effects. Immunotherapy, an approach to harness normal immune cells against cancers not only today's breakthrough but in fact the future of oncology therapeutics. Taking into consideration the recent approvals for new lines of therapy including anti-programmed-death-1 or programmed-death-1 ligand [PD-1/PD-L1] monoclonal antibodies for the treatment of Malignant Melanoma [MM] and Non-Small Cell Lung Cancer [NSCLC], local strategies need to be established following the field experts' concurrence. Expert input forums are among the key approaches to define locally-adapted clinical-pathways with regard to the novel treatments. To this end, a panel of Iranian medical oncology experts reviewed the available evidence, taking into consideration recent practice guidelines with regard to the treatment of MM and NSCLC in order to draw an agreed-upon approach highlighting the position of immunotherapy in their current practice. Having addressed the key questions and considering the possible limitations and challenges, the panel could reach an agreed position. This report highlights the discussions with regards to the role of immunotherapy in MM and NSCLC during the immune-oncology clinical forum [IOCF] comprising an Iranian panel of experts
ABSTRACT
Stroke is a significant public health burden which absolutely requires more effective therapies. The approved treatment options for stroke including tissue plasminogen activators, antiplatelet agents and anticoagulants mainly bear antithrombotic effects. Meanwhile, evolving investigational approaches such as collateral therapeutics and neuroprotective agents has thus far been attempted with equivocal effects on stroke outcome. The basic structural and ultrastructural changes following acute ischemic stroke should be well-considered when trying to target oxidative stress and cell death pathways using neuroprotective agents. Clearly, the positive results of preclinical studies on neuroprotectives and collateral therapeutics in stroke do not necessarily translate to the true clinical benefits of these agents. As such, several large advance-phased trials have already failed to prove so. On the other hand, controversial results in clinical setting should not discourage further research endeavors on the same. Besides, the concurrent use of flow augmentation and neuroprotectives may serve further clinical benefits. Based on the available evidence, it appears that optimization of preclinical studies and further well-designed prospective clinical trials let neuroprotection possibly find its position in stroke management. The present paper discusses key preclinical and clinical studies on neuroprotectives towards improved outcome in acute ischemic stroke
ABSTRACT
The management of unresectable advanced, metastatic malignant melanoma [MM] and chemotherapy-resistant or refractory non-small cell lung cancer [NSCLC] has been an uphill challenge in clinical oncology. The advent of immunotherapy in cancer has put forward some new hopes to cover unmet needs in treating such cases. Immune-checkpoint inhibitors are among the well-supported options in the same vein. Alongside other cancer immunotherapy class-molecules, pembrolizumab [PZB], a programmed cell death protein 1 [PD-1] blocking antibody, has recently been approved both for MM and NSCLC. This report presents an overview of the clinical benefits of PZB in MM and NSCLC and highlights the clinical features of two eligible cases who have undergone immunotherapy using PZB
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Objectives: This study was designed to evaluate the psychometric features of the Persian version of the Fatigue Impact Scale [FIS-P] tool when used in Iranian MS patients.
Methods: 140 MS patients and the equivalent number of healthy controls completed the following assessments: FIS-P, Fatigue Severity Scale [FSS], SF-36 questionnaire and the Mini-Mental State Examination [MMSE].
Results: A significant inverse correlation between FIS and the quality of life [SF-36 assessment tool], as well as a positive and significant correlation with the FSS were noted. The Intraclass Correlation Coefficient [ICC] values for the inter-rater reliability for the physical, cognitive, and social sections and the whole questionnaire were 0.89, 0.86, 0.95 and 0.98, respectively. The FIS Persian version was shown to possess a high reliability [with a Cronbach's alpha of 0.953]. Likewise, the ICC values for the testretest reliability were 0.86, 0.87, 0.92 and 0.93 for the physical, cognitive, social subscales and the whole questionnaire, respectively. This suggested a high reliability for the FIS-P.
Discussion: With a proper validity and reliability, the Persian-version of FIS retains the capability for being used in the assessment of fatigue and evaluation of the treatment and rehabilitation effects on fatigue-related symptoms among Persian-speaking patients with MS
ABSTRACT
This study investigates the awareness and perception on "epilepsy" amongst biology teachers in Fars province, Iran. A sample of high school biology teachers in Fars province, Iran, filled out an investigator designed questionnaire including questions about their knowledge and attitude concerning "epilepsy". There were 17 questions in the questionnaire. Nine questions addressed the knowledge and the rest were about attitude and perception. Forty two teachers completed the questionnaires. More than two-thirds of the participants had a fairly desirable awareness about the definition; whereas, only approximately 40% knew something about the etiology and treatment of epilepsy. More than two-thirds of the participants had a positive attitude towards epilepsy; however, misconceptions and negative attitudes were observed. Educational programs for biology teachers and also other teachers are necessary to improve their knowledge, attitude and perception about epilepsy