Holistic approach to opioid use disorder: Think nitric oxide!

This review deals with opioid addiction, chronic pain, and an innovative, noninvasive technology with simultaneous, beneficial applications for both conditions. This technology, called passive simulated jogging device (GENTLE JOGGER, JD) targets addiction and pain by increasing endothelial nitric oxide (NO) bioavailability. It can be self-administered while sitting or lying without resorting to multitasking thereby allowing watching television or operating a computer while effortless, physical activity is produced from motorized foot pedals repetitively striking a bumper at 175-190 times per minute which adds small pulses to the circulation. This action increases shear stress (friction) to vascular endothelium that stimulates endothelial nitric oxide synthase (eNOS) to increase NO that decreases oxidative stress and inflammation, and, slows accelerated vascular ageing associated with opioids.Since the 1970s, clonidine, lofexidine, and dexmedetomidine have been used off-label to suppress opioid withdrawal symptoms precipitated by excessive release of norepinephrine. These pharmacotherapy aids to withdrawal and tapering opioid dosagadrenoceptor agonists that act through eNOS to inhibit norepinephrine. Increasing NO as with JD and/ or in conjunction with opioid agonists should help stabilization, tapering, withdrawal, and relapses stages of addiction. Nitric oxide as increased with JD technology is antinociceptive as demonstrated in chronic and subacute pain states, viz., fibromyalgia, osteoarthritis, peripheral arterial disease, delayed onset of muscle soreness (DOMS), and sickle cell disease. Jogging device decreases elevated blood pressure that is produced with physical inactivity, a risk to opioid use disorder (OUD). Thus, JD provides holistic, cost-effective approach to opioid addiction as well as chronic and subacute pain.

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Vitamin D deficiency exacerbates UV/endorphin and opioid addiction

Science Advances ◽

10.1126/sciadv.abe4577 ◽

2021 ◽

Vol 7 (24) ◽

pp. eabe4577

Author(s):

Lajos V. Kemény ◽

Kathleen C. Robinson ◽

Andrea L. Hermann ◽

Deena M. Walker ◽

Susan Regan ◽

...

Keyword(s):

Vitamin D ◽

Opioid Use Disorder ◽

Opioid Addiction ◽

Opioid Use ◽

Endogenous Opioid ◽

Evolutionary Advantage ◽

Seeking Behavior ◽

Genetic And Environmental Factors ◽

Dose Dependent ◽

Genetic Mouse Models

The current opioid epidemic warrants a better understanding of genetic and environmental factors that contribute to opioid addiction. Here we report an increased prevalence of vitamin D (VitD) deficiency in patients diagnosed with opioid use disorder and an inverse and dose-dependent association of VitD levels with self-reported opioid use. We used multiple pharmacologic approaches and genetic mouse models and found that deficiencies in VitD signaling amplify exogenous opioid responses that are normalized upon restoration of VitD signaling. Similarly, physiologic endogenous opioid analgesia and reward responses triggered by ultraviolet (UV) radiation are repressed by VitD signaling, suggesting that a feedback loop exists whereby VitD deficiency produces increased UV/endorphin-seeking behavior until VitD levels are restored by cutaneous VitD synthesis. This feedback may carry the evolutionary advantage of maximizing VitD synthesis. However, unlike UV exposure, exogenous opioid use is not followed by VitD synthesis (and its opioid suppressive effects), contributing to maladaptive addictive behavior.

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Lower limb wounds in diabetes: the challenges of wound healing

British Journal of Community Nursing ◽

10.12968/bjcn.2021.26.sup9.s20 ◽

2021 ◽

Vol 26 (Sup9) ◽

pp. S20-S24

Author(s):

Krishna Gohil

Keyword(s):

Wound Healing ◽

Peripheral Arterial Disease ◽

Patient Outcomes ◽

Lower Limb ◽

Holistic Approach ◽

Arterial Disease ◽

Delayed Wound Healing ◽

Early Referral ◽

Peripheral Arterial

Managing ulceration in the lower limb for a patient with diabetes can be complex and challenging, requiring a multiprofessional, patient-centred, holistic approach with early referral for specialist review as key. Any delay in referral and intervention can be catastrophic, as time is tissue. Peripheral arterial disease and neuropathy both contribute significantly to the delays in wound healing, and it is important to rapidly recognise the problems with an informed assessment and understand the possible reasons for delayed wound healing, so that management is appropriate, rapid referrals are made and patient outcomes are optimised. This article discusses some of the reasons why wound healing is complicated in those with diabetes as a comorbidity.

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Association of Carboxyhemoglobin Levels with Peripheral Arterial Disease in Chronic Smokers Managed at Dr George Mukhari Academic Hospital

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17155581 ◽

2020 ◽

Vol 17 (15) ◽

pp. 5581

Author(s):

Mashudu Nemukula ◽

Motetelo Alfred Mogale ◽

Honey Bridget Mkhondo ◽

Lizette Bekker

Keyword(s):

Nitric Oxide ◽

Peripheral Arterial Disease ◽

Arterial Disease ◽

Academic Hospital ◽

Convenience Sample ◽

Logistic Analysis ◽

Arterial Dilation ◽

Peripheral Arterial ◽

Arterial Damage ◽

Multivariate Logistic Analysis

Chronic cigarette smokers (CCS) are known to have elevated levels of carboxyhemoglobin (COHb). However, it is not known whether increased levels of COHb are associated with endothelial dysfunction (ED), and therefore the development of peripheral arterial disease (PAD). The aim of the study was to investigate the association of blood COHb and plasma nitric oxide (NO) levels, and whether it is an independent risk factor in the development of PAD among CCS at Dr George Mukhari Academic Hospital (DGMAH). A sample of 120 CCS with PAD and a convenience sample of 100 CCS without PAD were recruited into the study. Blood COHb levels were measured using the ABL 90 FLEX CO-oximeter automated spectroscopy. Plasma nitric oxide (NO) levels were measure using ELISA. Logistic regression analysis was used to investigate the association of blood COHb and plasma NO with PAD. Blood COHb levels of CCS with PAD were significantly higher than those of CCS without PAD, and the NO levels of CCS with PAD were significantly lower than those of CCS without PAD. Although both the blood COHb and plasma NO in CCS were significantly associated with PAD in bivariate logistic analysis, only plasma NO was independently associated with PAD in multivariate logistic analysis. This finding is consistent with the hypothesis that COHb is a cause of arterial damage in PAD, leading to reduced NO, and therefore reduced arterial dilation.

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Prevalence of Chronic Opioid use in Patients With Peripheral Arterial Disease Undergoing Lower Extremity Interventions

Journal of Vascular Surgery ◽

10.1016/j.jvs.2018.10.027 ◽

2019 ◽

Vol 69 (1) ◽

pp. e13-e14 ◽

Cited By ~ 1

Author(s):

Gabriela Velazquez-Ramirez ◽

Jonathan Krebs ◽

Jeannette Stafford ◽

Rebecca Ur ◽

Timothy Craven ◽

...

Keyword(s):

Peripheral Arterial Disease ◽

Lower Extremity ◽

Arterial Disease ◽

Opioid Use ◽

Chronic Opioid Use ◽

Peripheral Arterial

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Active phytoconstituents for diabetes management: A review

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2017-0123 ◽

2018 ◽

Vol 15 (3) ◽

Cited By ~ 2

Author(s):

Rajnish Gupta

Keyword(s):

Diabetes Management ◽

Sedentary Lifestyle ◽

Cost Effective ◽

Arterial Disease ◽

Current Treatment ◽

Chronic Complications ◽

Treatment Protocols ◽

Artery Disease ◽

Peripheral Arterial ◽

Antidiabetic Plants

AbstractDiabetes is a metabolic syndrome increasing rapidly due to occupational stress, lack of physical activity, sedentary lifestyle and increasing occurrence of obesity, associated with rapidly growing urbanization and industrialization. Due to erroneous carbohydrate metabolism, diabetics are more prone to chronic complications like nephropathy, neuropathy, retinopathy, coronary artery disease and peripheral arterial disease resulting in tissue damage. Current treatment protocols to these problems produce more serious adverse effects and are costly too. Medicinal plants provide an alternative of safe, reliable and cost-effective pharmacological source to all these ailments. This review provides the compiled data of isolated active phytoconstituents of 22 potent antidiabetic plants with their plant-part used, which might be useful for drug development.

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Imbalance between nitric oxide generation and oxidative stress in patients with peripheral arterial disease: Effect of an antioxidant treatment

Journal of Vascular Surgery ◽

10.1016/j.jvs.2006.05.023 ◽

2006 ◽

Vol 44 (3) ◽

pp. 525-530 ◽

Cited By ~ 40

Author(s):

Lorenzo Loffredo ◽

Pasquale Pignatelli ◽

Roberto Cangemi ◽

Paola Andreozzi ◽

Maria Antonietta Panico ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Peripheral Arterial Disease ◽

Arterial Disease ◽

Antioxidant Treatment ◽

Disease Effect ◽

Peripheral Arterial ◽

And Oxidative Stress

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Cost-effectiveness of Comprehensive screening of general population for hypertension: Can it save money and Life? Systematic review of Pharmacoeconomic Studies

10.21203/rs.2.24367/v1 ◽

2020 ◽

Author(s):

Majid Davari ◽

Mende Mensa Sorato ◽

Shekoufeh Nikfar

Keyword(s):

Risk Factors ◽

Cost Effectiveness ◽

General Population ◽

Adult Population ◽

Cost Effective ◽

Arterial Disease ◽

Population Based ◽

Delayed Presentation ◽

Early Screening ◽

Peripheral Arterial

Abstract Background: Hypertension is one of major modifiable risk factors contributing for development of ischemic heart disease, diabetes, kidney disease, cerebrovascular disease and peripheral arterial disease. Silent nature of the disease, delayed presentation of patients to health system after development of significant cardiovascular events and poor access to comprehensive health care are major challenge of hypertension control. Early screening, detection and treatment of hypertension is effective for control of the disease progression. However, there is no robust evidence on whether screening general population for hypertension is cost-effective or not. Therefore, this review was conducted t o generate evidence on cost effectiveness of population-based hypertension screening for asymptomatic individuals as early detection strategy for the primary prevention of cardiovascular diseases. Methods: PubMed/Medline , Scopus, Web of sciences and Google Scholar were searched from January 2000 to 11 December 2019. Two investigators independently selected and reviewed fair and good-quality pharmacoeconomic studies for the cost-effectiveness of asymptomatic screening for hypertension in the community. Quality of selected literatures are evaluated by authors based on comprehensive tool developed for critical appraisal of pharmacoeconomic studies. Results: Eleven included Pharmacoeconomic studies reported favorable results for screening asymptomatic adults for hypertension. Most of studies agreed on cost-effectiveness of screening adults aged 40 years and older. Screening of general adult population for hypertension is not-cost effective. Conclusion: Screening population 40 years and older with or without additional risk factors is cost-effective in reducing hypertension and associated cardiovascular disease morbidity and mortality in developed and developing countries.

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