14 Matching Annotations
  1. Apr 2022
  2. Feb 2022
  3. Nov 2021
  4. Oct 2021
    1. The kappa agonist spiradoline failed to produce cross-sensitization, but coadministration of spiradoline prevented morphine and buprenorphine from producing cross-sensitization. The ability of spiradoline to block cross-sensitization was itself blocked by the kappa antagonist nor-binaltorphimine.

      This suggests to me that it is the opioid tolerance itself that determines cocaine sensitivity. To test this, I'd like to see a study that administers a KOR agonist after tolerance to opioids has been established, and see if this reverses cocaine sensitivity.

  5. Sep 2021
    1. Đọc sách nghe tưởng chừng là việc quen thuộc và phức tạp vô cùng đối với nhiều người mà lại trở nên đơn giản đến không tưởng với cách diễn tả sâu sắc qua từng câu chuyện của tác giả Phan Thanh Dũng.

  6. Aug 2021
    1. At lower doses (0.18 mg/kg and 0.32 mg/kg) we observed no prolonged effect on KOR binding but at 0.60 mg/kg salvinorin A induced a sustained decrease in KOR binding (BPND decreased by 40–49%) which persisted up to 2.5 h post administration, long after salvinorin A had been eliminated from the brain. These data point towards an agonist-induced adaptive response by KOR, the dynamics of which have not been previously studied in vivo with PET.

      This may partly represent the salvia "afterglow". It also demonstrates how rapidly tolerance-like mechanism can occur.

      I find it odd that 0.32 mg/kg had little prolonged effect when twice that dose had a very large effect. I'd expect more of a gradient. The graph (figure 4) shows a nonsignificant drop in KOR binding of ~13% at 1 hour at 0.32 mg/kg, which I'm certain would become statistically significant in a larger sample. Still, that's nowhere near the 45% seen at 0.6 mg/kg. At 0.18 mg/kg, we see ~9%.

      I calculated the human equivalent dose to be 6.8mg (0.6mg0.16270). This is an very high dose, so likely does not represent an accurate dose conversion.

  7. Jul 2021
    1. Collectively, these results indicate that mirtazapine may help to maintain abstinence in opioid dependent patients.

      I concur. This merits human analysis. I'd be curious to know the subjective effects of combining the two. In particular, I'm wondering if mirtazapine reduces "wanting" while enhancing "liking".

      The main reason I'd been thinking this is due to comparison to similar drug combos in humans. I'd heard that combining hydroxyzine and opioids was sometimes prescribed to enhance the effectiveness of opioids and/or use lower opioid doses; I'd also read on some harm reduction forum that some people enjoy combining opioids with antihistamines. Given that mirtazapine is to a large extent just hydroxyzine but with added adrenergic effects, it seems likely that much of these data can be cross-applied (between mirtazapine and hydroxyzine in particular).

  8. Mar 2021
    1. The decrease in total activity count and phase delay of onset of the activity rhythm caused by ethanol were partially antagonized by theophylline.

      I think the takeaway is that theophylline may help with phase delay. Though, that is merely my thoughts at first glance. Not to mention that this is rat data. Nonetheless, combining this with data on the cAMP and cGMP role in circadian rhythm, I'm relatively confident that methylxanthines have some effect on circadian rhythm. Most likely phase advancing effects.

      In practice, this means theobromine should be explored as a treatment for Delayed Sleep Phase syndrome (DSPS). It may also be useful for some non-24 conditions. I may consider upping my theobromine dose so that I can get to sleep early and wake up early.

      Also, perhaps I should avoid ethanol in the morning. Hard to say from this data.

  9. Dec 2020
    1. The 5-HT2 antagonists reportedly produce a paradoxical down-regulation of 5-HT2 binding sites upon chronic treatment, rather than the expected supersensitivity. Chronic treatment with ritanserin (2.5 mg/kg/day for 7 days), but not mianserin (same regimen), attenuated a QMWS 24 h after the final injection, thus supporting with a functional measure, the down-regulation of such binding sites by ritanserin.

      Are they saying that mianserin did not downregulate the receptors? That's what it sounds like. Most likely this is just because it is a weaker antagonist than ritanserin.

  10. Nov 2020
    1. Rosemary enhanced the protective efficacy of AREDS and led to the greatest effect on the retinal genome in animals reared in high environmental light. Chronic administration of rosemary antioxidants may be a useful adjunct to the therapeutic benefit of AREDS in slowing disease progression in AMD.

      This is not in the least surprising. Dietary antioxidants also protect the skin during sunlight exposure.

      Oxidative stress likely also plays a role in diabetic retinopathy. It plays a role in the aging process itself. That said, there is probably a limit to protective powers of antioxidants. Nonetheless, I don't think that that limit has ever been realized in any population. I doubt we've even come close in rats.

  11. Oct 2020
    1. Cognitive Presence “is the extent to which learners are able to construct and confirm meaning through sustained reflection and discourse” (Community of Inquiry, n.d, para. 5). Video is often used as a unidirectional medium with information flowing from the expert or instructor to the learner. To move from transmission of content to construction of knowledge, tools such as Voice Thread (VoiceThread, 2016) support asynchronous conversation in a multimedia format.

      The author, Kendra Grant, is the Director of Professional Development and Learning for Quillsoft in Toronto Canada. Grant helps business succeed in education design and support. In this article Grant discusses how quickly the learning environment has changed through technological development. Grant explores the RAT Model, which guides instructors in the "use of technology to help transform instructional practice." Grant then examines the Community of Inquiry model, which seeks to create meaningful instruction through social, cognitive and teaching presence. Grant concludes by providing general principles for creating a positive video presence.

      Rating: 8/10

  12. Aug 2020
    1. The RAT model sees software development as an off-line program-construction activity composed of these parts: defining, decomposing, estimating, implementing, assembling, and finishing

      This is what can lead to the 'there is only version 1.0' problem - and improvements / iterations fall to the sidelines.

      This can have a number of consequences

      • over designed / engineered
      • doing unnecessary work
      • lack of user feedback and ability to accommodate it
      • rigid / fragile architecture
  13. Feb 2018