Medical hypotheses
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Comparative Study
An extension of hypotheses regarding rapid-acting, treatment-refractory, and conventional antidepressant activity of dextromethorphan and dextrorphan.
It was previously hypothesized that dextromethorphan (DM) and dextrorphan (DX) may possess antidepressant properties, including rapid and conventional onsets of action and utility in treatment-refractory depression, based on pharmacodynamic similarities to ketamine. These similarities included sigma-1 (σ(1)) agonist and NMDA antagonist properties, calcium channel blockade, muscarinic binding, serotonin transporter (5HTT) inhibition, and μ receptor potentiation. Here, six specific hypotheses are developed in light of additional mechanisms and evidence. ⋯ Suggestions include exclusionary criteria, oral dosing, observation periods, dose-response approaches, and safety and tolerability are considered. Although oral dextromethorphan may be somewhat more likely to show efficacy through complementary antidepressant mechanisms of dextrorphan, a clinical trial will be more logistically complex than one of Nuedexta due to high doses and plasma level variability. Clinical trials may increase our therapeutic armamentarium and our pharmacological understanding of treatment-refractory depression and antidepressant onset of action.
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Osteosarcoma is the most common primary malignant tumor of bone. Except for the improvement in five-year survival achieved by the adoption of neoadjuvant chemotherapy strategy, there are nearly no improvement for the treatment of osteosarcoma in the past 30 years, especially for the patients with metastatic disease. Immunotherapy has been successfully applied in some tumors. ⋯ We believe that CAR expressing T cells constructed by this strategy would persist longer and are more effective to eradicate osteosarcoma cells. In addition, this treatment strategy is an individualized treatment because an effective target specific to the CAR could be found. Therefore the immune escape of osteosarcoma would be surmounted and the survival of patients would be improved.
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Bright light therapy (BLT) is widely accepted as first-line treatment of seasonal affective disorder (SAD). However, the mechanism of action of BLT is still widely unknown. On the other hand, in mammals, light penetrates the skull bone and reaches the brain, and extra ocular transcranial phototransduction has physiological influences such as changed reproductive cycles and increased brain serotonin levels. ⋯ In conclusion, it is hard to believe that our findings could be explained solely by placebo effect. Consequently, the basic assumptions underlying extraocular photoreception in humans deserve to be reconsidered. Given that a proper placebo treatment can be implemented via ear canals, further investigations with randomized placebo-controlled and/or dose-finding study designs regarding the extraocular transcranial bright light in the treatment of SAD are called for.
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We assessed the changes in cerebrospinal fluid (CSF) hydrodynamics caused by barriers to CSF circulation, and determined the relationship between CSF velocity and intracranial pressure in the aqueduct of the midbrain. This was determined by correlating the CSF peak flow velocity with the intracranial pressure (ICP) obtained from a lumbar puncture (LP) procedure. The CSF peak flow velocity was measured by finger pulse-gated cine-phase contrast (PC) MR scan 8-12 hours after LP was performed in 28 patients. ⋯ However, varying degrees of the hydrocephalus were observed in those patients who demonstrated a cranial direction of the CSF net flow. Our results indicate that non-invasive measurement of the CSF peak flow with cine-PC MR imaging can be related to the change of CSF circulation caused by the obstructions to the CSF circulation in the patients with various neurological disorders. This unique method may be a substantially useful tool to assess the changes in the ICP in the directional pattern.
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There is no denying that opioids are the most important analgesic drugs which are widely used in clinical situations. Still, prolonged administration of these drugs can cause to reduce their analgesic efficacy due to the development of tolerance. ⋯ As studies show, over-activity in cyclo-oxygenase pathways and production of prostaglandins due to long-term exposures of opioid have a critical role in the development of tolerance to antinociceptive effect of opioid, hyperalgesia, and opioid dependence. The present study aims at suggesting the hypothesis that through blending a non-steroid anti-inflammatory drug with opioid actively causes reduction in unwanted effects of opioid i.e. by inhibition of opioid-induced cyclo-oxygenase overactivity whereas it is well-known that the combination therapy via reducing opioid dosage reduces the unwanted effects.