Simply Calming


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First, an introduction or just skip below to web link, below, of the sweet Suzuki Roshi breathing practice of exhalation. It is so simple people with Alzheimer’s can do it. So instantly calming.

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It is best to practice while we are young and build a solid practice, make it part of being with your Self. The Divine Self. It is so simple and so sweet. It is who we are.

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A wonderful practice and highest teaching. We are all the divine essence, the serene soul. Enjoy how simple and calming…..relax and be in the moment of which the highest teachings speak, as far back as the Vedas and Upanishads, Buddha and all spiritual traditions have taught. 

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There is no god but God. There are no other gods. Not dreamy woo woo stuff. It just Is. Omnipresent. 

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“This is no world. It is God Himself. In delusion we call it world.” Vivekananda (6:371) “Complete self-surrender is the only way to spiritual illumination. Vivekananda (5:258)

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Acceptance. Enjoy who you already are. 

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Just be. You are That. We forget our true self. This is real. No kids play. 

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We all experience these moments. Being. Just being. Simple as breathing. 

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“ There is no question that breathing is taking place. Can you see that there is no breather to be found anywhere? The body is empty, the breath is empty and you are empty.” 

 

The Upanishads describe that stage as turiya pure consciousness. Turiya is the background that underlies and transcends the three common states of consciousness.

Buddhists call this emptiness. Advaita calls it fullness. The Divine Essence. God. The self that merges into the Absolute beyond, time space and causation Beyond name and form there is nothing else but the Self, Existence-Consciousness-Bliss. And this pure simple breathing out brings it into this very moment.

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from the dharma message of Zen priest and teacher White Lotus Judith Ragir.

click above name to go directly to the website for this  dharma teaching – it will be easier to read. 

 

Exhaling and dissolving.

Here are some quotes from Suzuki Roshi in “Not Always So” (chapter: Calmness of Mind) that emphasize working with the exhale while meditating:

Calmness of mind is beyond the end of your exhalation. If you exhale smoothly, without even trying to exhale, you are entering into the complete perfect calmness of your mind. You do not exist anymore. 

Inhaling without effort you naturally come back to yourself with some color or form. Exhaling, you gradually fade into emptiness – empty, white paper. That is shikantaza. The important point is your exhalation. Instead of trying to feel yourself as you inhale, fade into emptiness as you exhale. 

To take care of the exhalation is very important. To die is more important than trying to be alive. When we always try to be alive, we have trouble. Rather than trying to be alive or active, if we can be calm and die or fade away into emptiness, then naturally we will be all right. Buddha will take care of us. Because we have lost our mother’s bosom, we do not feel like her child anymore. Yet fading away into emptiness can feel like being at our mother’s bosom, and we will feel as though she will take care of us. Moment after moment, do not lose this practice of shikantaza.” 

This is very impressive quote to me. It is in alignment with the fourth Tetrad of the Anapanasati Sutra. The Anapanasati Sutra is composed of sixteen contemplations, which divide rather neatly into four sets of four: The body group, the feelings group, the mind group, and the wisdom group. They are in a “somewhat” developmental order in that mindfulness of the physical movements of the breath is the first emphasis in any concentration practice. The feelings group is ***becoming sensitive to rapture and joy in meditation***and then calming or letting go of rapture. The third group is the mind group – becoming aware of the mind, gladdening the mind, steadying the mind, and liberating the mind. (See “Breath by Breath” by Larry Rosenberg. This is a book Clouds in Water studied several years ago).

The fourth group the wisdom group is very similar to Suzuki Roshi’s quote above.

From a Thich Nhat Hanh translation:

13. I am breathing in and observing the impermanent nature of all dharmas. I am breathing out and observing the impermanent nature of all dharmas. He practices like this.

14. I am breathing in and observing the fading of all dharmas. I am breathing out and observing the fading of all dharmas. She practices like this.

15. I am breathing in and observing liberation (cessation). I am breathing out and observing liberation (cessation). He practices like this.

16. I am breathing in and observing letting go (relinquishment). I am breathing out and observing letting go (relinquishment). She practices like this.

This sutra demonstrates how the breath can take you all the way to the deepest realizations. The breath often is used as the first object of concentration. But it also can practiced as a complete teaching which leads to insight.

In Larry Rosenberg’s book, he writes about Buddhadasa’s approach to breath practice and its use for going all the way to realization. He writes:

“ When we got to the thirteenth contemplation – which concerns impermanence, this is where real vipassana begins – he said that Anapanasati was one of the simplest and most effective means for realizing emptiness.” 

Buddhadasa said: “There is no question that breathing is taking place. Can you see that there is no breather to be found anywhere? The body is empty, the breath is empty and you are empty.” 

Perhaps this is where Zen and Vipassana meet. Where the Mahayana and the Theravada come to the same conclusion.

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.http://www.judithragir.org/2014/01/exhaling-and-dissolving/

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.Adds are not mine. 

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Ketamine in Bipolar Depression – A Review


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An excellent review of Ketamine, a rapid-acting antidepressant and anti-suicidal agent, in Bipolar Depression

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Efficacy of Ketamine in Bipolar Depression: Systematic Review and Meta-analysis. 

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Parsaik AK1, Singh B, Khosh-Chashm D, Mascarenhas SS.

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OBJECTIVE: To consolidate the evidence from the literature to evaluate the role of ketamine in the treatment of bipolar depression.

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METHODS: Major databases, including MEDLINE, EMBASE, Cochrane, and Scopus, were searched through October 2014, for studies reporting the role of ketamine in the treatment of bipolar depression. Only randomized controlled trials were included in the meta-analysis. We calculated standardized mean differences (SMDs) with SE for each study included in the meta-analysis. A random effect model was used to calculate the pooled SMDs. Heterogeneity was assessed using the Cochran Q test and I statistic.

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RESULTS: Of the 721 articles that were screened, 5 studies that enrolled a total of 125 subjects with bipolar depression (mean age, 44.6+/-4.3y and 65.6% females) were included in the systematic review; 3 randomized controlled trials (69 subjects) were included in the meta-analysis. The meta-analysis showed significant improvement in depression among patients receiving a single dose of intravenous ketamine compared with those who received placebo (SMD=-1.01; 95% confidence interval, -1.37, -0.66; P<0.0001). The maximum improvement was observed 40 minutes after the ketamine infusion. No heterogeneity was observed between the studies (Cochran Q test P=0.38, I=0%). The 2 studies that were excluded from the meta-analysis also showed significant improvement in depression after ketamine therapy. Individual studies also reported improvement in anhedonia and suicidal ideation after ketamine therapy. None of the subjects had serious side effects, and the side effects were similar between the ketamine and placebo groups.

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CONCLUSIONS: This study suggests that ketamine is effective in treatment-resistant bipolar depression and may reduce suicidal ideation and anhedonia.

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The material on this site is for informational purposes only, and is not a substitute for medical advice,

diagnosis or treatment provided by a qualified health care provider.

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If you wish an appointment, please telephone my office.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Analgesic Response to Ketamine Linked to Circulating microRNA in Complex Regional Pain Syndrome


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Analgesic Response to Intravenous Ketamine

Is Linked to a Circulating microRNA Signature

in Female Patients

With Complex Regional Pain Syndrome

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The ability to measure Micro RNS’s (miRNA) in blood looks like it may become an important tool someday once it is available for the clinic. It could be used to predict if your condition will respond to various medications.

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MicroRNAs are emerging as important modulators of various psychiatric (schizophrenia, bipolar disorder) and neurological conditions including pain, epilepsy, cognitive dysfunction, neuronal development, structure and function. “MicroRNAs are small, non-coding RNAs that act as post-transcriptional regulators of gene expression.  miRNA’s can be affected by morphine and affected by other drugs. It is hoped that complex clinical phenotypes may be profiled in assays of peripheral blood and may predict response to treatment such as in this study. Ketamine is given for selected patients that have failed to respond to standard treatment.

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This research was published in Pain, June 2015, by Professor Schwartzman’s group at Drexel University. Seven of his patients with Complex Regional Pain Syndrome were ketamine responders and 6 were poor responders. They note that, “Although [ketamine] treatment is generally effective, approximately 30% of patients have an inadequate response to ketamine.”

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“Stability in circulation and dysregulation in disease state are 2 features making extracellular miRNAs useful candidates for biomarker discovery. Alterations in miRNA profiles have been reported for rheumatoid arthritis and systemic lupus erythematosus as well as for painful conditions such as irritable bowel syndrome, chronic bladder syndrome, endometriosis, and migraine. Cerebrospinal fluid from patients with fibromyalgia showed differential expression of 9 miRNAs.”

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Quoting directly from the article:

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Highlights

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•We studied ketamine treatment–induced miRNA alterations in blood from patients with CRPS.
•Differential miRNA expression was observed in whole blood before and after treatment.
•Before therapy, 33 miRNAs differed between responders and poor responders.
•Lower pretreatment levels of miR-548d-5p may contribute to higher UDP-GT activity.
•Circulating miRNAs can be potential biomarkers in predicting treatment response.

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From the Abstract

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Investigation of the mechanistic significance of hsa-miR-548d-5p downregulation in poor responders showed that this miRNA can downregulate UDP-glucuronosyltransferase UGT1A1 mRNA. Poor responders had a higher conjugated/unconjugated bilirubin ratio, indicating increased UGT1A1 activity. We propose that lower pretreatment levels of miR-548d-5p may result in higher UDP-GT activity, leading to higher levels of inactive glucuronide conjugates, thereby minimizing the therapeutic efficacy of ketamine in poor responders.

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Perspective

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This study suggests the usefulness of circulating miRNAs as potential biomarkers. Assessing miRNA signatures before and after treatment demonstrated miRNA alterations from therapy; differences in miRNA signature in responders and poor responders before therapy indicate prognostic value. Mechanistic studies on altered miRNAs can provide new insights on disease.

 

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From the Discussion

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Ketamine is also considered to be the prototype for a new generation of glutamate- based antidepressants that can alleviate depression within hours of treatment. Several biological measures have been explored to characterize treatment response and to gain insight into mechanisms underlying the rapid antidepressant effects of ketamine. A plasma metabolomics study in patients with bipolar depression suggested that the basal mitochondrial b-oxidation of fatty acids differed between responders and nonresponders to ketamine. Other studies have shown differences in baseline plasma concentrations of D-serine, serum levels of interleukin 6, and plasma levels of Shank3, a postsynaptic density protein involved in NMDA receptor tethering and dendritic spine rearrangement.

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Differences in the ability to metabolize ketamine because of interindividual differences and pharmacogenetic factors have been proposed to contribute to the varied responses to ketamine therapy and its clinical outcome. Similar conclusions have been drawn for patients with depression; plasma from patients with treatment- resistant bipolar depression who had undergone a single 40-minute infusion of a subanesthetic dose of ketamine showed that although NK is an initial metabolite, it is not the major circulating metabolite. This again suggests that other downstream metabolites of ketamine may play a role in the pharmacological effects of the drug. It is also known that (2S,6S)-hydroxynorketamine is an active and selective inhibitor of the a7 subtype of the nicotinic acetylcholine receptor; this activity was shown to contribute to the pharmacological responses associated with the antidepressant activity of (R,S)-ketamine. We postulate that in patients with CRPS, 1 factor contributing to resistance is an altered pharmacokinetic profile produced by enhanced elimination of active metabolites downstream of NK, which is mediated by hsa-miR-548d-5p. However, because we have relied on indirect evidence of a higher percentage of direct/indirect bilirubin in poor responders, indicating increased UDP-GT enzyme activity, additional studies investigating hydroxynorketamine and its downstream metabolites along with their glucuronide conjugates in plasma and urine will provide direct evidence for the role of miR-548d-5p in mediating response to ketamine therapy in responders and poor responders.

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They noted a significant difference in body weight between responders and nonresponders (heavier), but not in duration of disease and analgesic response to ketamine. Toward that end, they will publish separately upon

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… investigating the link between miR-34a, which showed 28-fold reduction in poor responders relative to responders (Table 2), and the neuroendocrine system….

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From the Conclusion

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Our studies showed that miR-548d-5p can regulate UDP-GT but not CYP3A4, suggesting that UDP-GT activity in responders and poor responders may be mediated by differences in the level of circulating miR-548d-5p. Lower levels of miR-548d-5p in poor responders before treatment could result in higher UDP-GT activity, leading to the production of more inactive glucuronide conjugates and faster elimination of active ketamine metabolites downstream of NK. Thus, the levels of hsa-miR-548d-5p could minimize the therapeutic efficacy of ketamine and pain relief. Differences in miRNA signature can thus provide molecular insights distinguishing responders from poor responders. High failure rates of drugs targeted to treat neuropathic pain warrant changes in approaches. Studies targeting well-defined patient populations for clinical trials will play a crucial in developing drugs that may be efficacious in a subset of patients. Extending this approach to other treatment and outcome assessments might permit stratification of patients for maximal therapeutic outcome.

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How frustrating it is for patients and family who must cope with an intractable condition such as pain or Bipolar Disorder or treatment resistant Major Depression that has failed all commonly prescribed medications. For all of them, we need changes in approach.

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“High failure rates of drugs targeted

to treat neuropathic pain

warrant changes in approaches.”

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Perhaps scientists reading this would comment upon how it may relate to tolerance as it differentially occurs in those receiving intermittent ketamine vs continuous intravenous infusion.

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Dysregulation of miRNA’s has been shown in psychiatric disorders including depression and schozophrenia, neurodevelopmental disorders, cognitive dysfunction,  epilepsy, chronic pain states with implication for the cause and treatment of these disorders.

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Research targeting miRNA’s as novel treatment for depression has shown that chronic fluoxetine, repeated electroconvulsive shock therapy, and acute ketamine have the capacity to alter hippocampal miRNA levels.

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It is hoped these tests may be available someday clinically as the cost of off-label treatment not covered by insurance is a great burden for those already disabled by intractable pain or treatment resistant depression.

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PUBLIC WARNING

warning reprinted with permission of Demitri Papolos, MD
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Ketamine is a controlled substance.
Administered improperly, or without the guidance of a qualified doctor,
Ketamine may cause injury or death.
No attempt should be made to use Ketamine
in the absence of counsel from a qualified doctor.

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The material on this site is for informational purposes only.
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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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This site is not for email and not for appointments.

If you wish an appointment, please telephone the office to schedule.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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