δ-Tocotrienol plus AHA Step-1 diet in hypercholesterolemic subjects caused reductions in lipid parameters (14% to 18%) with 250 mg/d dose, and 500 mg/d resulted induction in these parameters. Although, α-tocopherol is the most bioavailable form of vitamin E. There are few reports on bioavailability of tocotrienols in humans. Pharmacokinetics and bioavailability of δ-tocotrienol was quantified on plasma levels of tocol isomers, cytokines, and microRNAs. Subjects were fed doses of 125 mg/d to 500 mg/d. Plasma samples collected between 0 h to 10 h, levels of tocols estimated by HPLC, which resulted dose-dependent increases in AUC0-10, Cmax0-∞, Tmaxh, t1/2h, Cl-T 1/h, Vd/f, keh-1. Maximum plasma levels of δ-tocotrienol were at 3 h (125 mg/d to 250 mg/d), 6 h (500 mg/d). Effects of 32 compounds were evaluated on TNF-α secretion, nitric oxide production, and gene expression (TNF-α, IL-1β, IL-6, iNOS activity) in PPAR-α knockout mice. Anticancer activities of thiostrepton, dexamethasone, 2-methoxyestradiol, δ-tocotrienol, quercetin, amiloride, quinine sulfate showed significant anti-proliferative properties in Hela cells, pancreatic, prostate, breast, lungs, melanoma, B-lymphocytes, T-cells (40% to 95%). Results of plasma total mRNAs after δ-tocotrienol feeding to hepatitis C patients revealed significant down-regulated gene expression of pro-inflammatory cytokines. A mixture of δ-tocotrienol, resveratrol, vitamin D3 (NS-3) were given two capsules/d or cellulose/olive oil as placebo to individuals with T2DM (24-weeks). Significant down-regulation (15% to 74%) of gene expression in diabetes biomarkers and decreases i n serum levels of fasting-glucose, HbA1c, hs-CRP, fasting-insulin, HOMA-IR, MDA (9% to 23%) were observed with NS-3 treated T2DM. Pure plasma mRNAs and miRNAs of pre-dose vs. post-dose of NS-3 treated samples were analyzed by Next Generation Sequencing (NGS). Venn diagrams have established genetic regulatory network images and canonical signaling pathways for mRNA, miRNA, and paired mRNA-miRNA.
Inflammation has been implicated in cardiovascular disease and tocotrienols are potent hypocholesterolemic agents that reduce β-hydroxy-β-methyl-glutaryl coenzyme A reductase activity, which is degraded via the ubiquitin-proteasome pathway. Impact of various tocotrienols (α-, γ-, or δ-tocotrienol) treatments inhibit the chymotrypsin-like activity of 20S rabbit muscle proteasome (>50%) in RAW 264.7 cells and BALB/c mice. Moreover, the effect of various tocotrienols (α-, γ-, or δ-tocotrienol), α-tocopherol, quercetin, riboflavin, (-) Corey lactone, amiloride, dexamethasone supplemented diets fed to chickens (4-weeks) resulted in reduction of total cholesterol, LDL-cholesterol, and triglycerides. This trend was also observed in macrophages from RAW 264.7 cells, in LPS-induced thioglycolate-elicited peritoneal macrophages derived from C57BL/6, BALB/c, LMP7/MECL-1-/-, and PPAR-α-/- knockout mice from young (4-week-old) and senescent (42-week-old) mice, resulting in significant inhibition of TNF-α and nitric oxide levels (30% to 70%), blocked degradation of P-IκB protein, and decreased activation of NF-κB, followed gene suppression of mRNA levels of TNF-α, IL-1β, IL-6, and iNOS. In human study, normal or hypercholesterolemic subjects administered two capsules/d of NS-7 or NS-6 (4-weeks) showed decrease in serum CRP, NO, γ-GT, total cholesterol, LDL-cholesterol, and triglycerides levels in normal as compared to hypercholesterolemic subjects (12% to 39%). In second study, hypercholesterolemic subjects were given increasing doses of δ-tocotrienol (125 mg, 250 mg, 500 mg, and 750 mg/day) plus AHA Step-1 diet (4-weeks). The most effective dose of tocotrienols (250 mg/day) may be used to lower serum NO (40%), CRP (40%), MDA (34%), γ-GT (22 %), and inflammatory cytokines IL-1α, IL-12, IFN-γ by 15% to 17%, and increase TAS levels by 22%.
This is the first description of a procedure targeting the myofascial tissues since Janet Travell's description of myofascial trigger points in 1942. However unlike trigger point injections, this minimally invasive myofascial nerve injection is performed differently and targets the myofascial tissues, peripheral innervations, posterior spinal structures and spinal nerve roots at the same time. It is different from a trigger point injection that aims to block trigger points within a muscle. Prolonged standing or sitting, posture and other multiple factors can create recurrent injuries with attendant inflammation and episodically aggravate pain. Thus there is a need for a simple intervention technique that can be performed from the medical clinic to the battlefield to quickly relieve inflammation and prevent chronic pain.
Background: There is expanding knowledge about the phenotypic variability of patients with voltage gated potassium channel complex (VGKC) antibody mediated neurologic disorders. The phenotypes are diverse and involve disorders of the central and peripheral nervous systems. The central nervous system manifestations described in the literature include limbic encephalitis, status epilepticus, and acute encephalitis.
Patient description: We report a 4.5 year-old boy who presented with intractable Myoclonic Astatic Epilepsy (MAE) or Doose syndrome and positive VGKC antibodies in serum. Treatment with steroids led to resolution of seizures and electrographic normalization.
Conclusion: This case widens the spectrum of etiologies for MAE to include autoimmunity, in particular VGKC auto-antibodies and CNS inflammation, as a primary or contributing factor. There is an evolving understanding of voltage gated potassium channel complex mediated autoimmunity in children and the role of inflammation and autoimmunity in MAE and other intractable pediatric epilepsy syndromes remains to be fully defined. A high index of suspicion is required for diagnosis and appropriate management of antibody mediated epilepsy syndromes.