Long-Term (5 Years), High Daily Dosage of Dietary Agmatine—Evidence of Safety: A Case Report

Gad M. Gilad,Varda H. Gilad 한국식품영양과학회 2014 Journal of medicinal food Vol.17 No.11

There is presently a great interest in the therapeutic potential of agmatine, decarboxylated arginine, for various diseases. Recent clinical studies have already shown that oral agmatine sulfate given for up to 3 weeks provides a safe and, as compared with current therapeutics, more effective treatment for neuropathic pain. These studies have ushered in the use of dietary agmatine as a nutraceutical. However, in view of information paucity, assessment of long-term safety of oral agmatine treatment is now clearly required. The authors of this report undertook to assess their own health status during ongoing consumption of a high daily dosage of oral agmatine over a period of 4–5 years. A daily dose of 2.67 g agmatine sulfate was encapsulated in gelatin capsules; the regimen consists of six capsules daily, each containing 445mg, three in the morning and three in the evening after meals. Clinical follow-up consists of periodic physical examinations and laboratory blood and urine analyses. All measurements thus far remain within normal values and good general health status is sustained throughout the study period, up to 5 years. This case study shows for the first time that the recommended high dosage of agmatine may be consumed for at least 5 years without evidence of any adverse effects. These initial findings are highly important as they provide significant evidence for the extended long-term safety of a high daily dosage of dietary agmatine—a cardinal advantage for its utility as a nutraceutical.

Garlic Allicin as a Potential Agent for Controlling Oral Pathogens

Gilad Bachrach,Areen Jamil,Ronit Naor,Golan Tal,Zvi Ludmer,Doron Steinberg 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.11

Garlic has been used medicinally throughout human history. Allicin is considered the most therapeutic constituent of garlic. This study tested the antimicrobial activity of garlic allicin on oral pathogens associated with dental caries and periodontitis. Allicin was found effective against all the tested bacteria. The broth dilution method revealed that planktonic growth of the cariogenic, gram-positive species Streptococcus mutans, S. sobrinus, and Actinomyces oris was inhibited by an allicin concentration of 600 μg/mL or higher. Planktonic growth of the tested gram-negative periopathogenic species Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum was inhibited by a minimum allicin concentration of 300 μg/mL. Porphyromonas gingivalis, an anaerobic, gram-negative pathogen and the bacterium most associated with chronic periodontitis, demonstrated the lowest sensitivity to allicin (2,400 μg/mL). Gel zymography and the synthetic chromogenic substrate N_α-benzoyl-L-arginine 4-nitroanilide hydrochloride demonstrated that allicin inhibits the proteases of P. gingivalis, including the arginine and lysine gingipains known as major virulence factors of this organism. A gingipain-inactivated mutant demonstrated high sensitivity to allicin (<300 μg/mL), revealing that gingipains confer resistance to allicin. Live/dead staining followed by analysis with confocal laser scanning microscopy revealed that allicin was bactericidal to S. mutans grown in mature biofilms. However, this bactericidal effect was reduced as biofilm depth increased. In conclusion, these results support the traditional medicinal use of garlic and suggest the use of allicin for alleviating dental diseases.

Synergistic amplification of beta-amyloid- and interferon-gamma-induced microglial neurotoxic response by the senile plaque component chromogranin A.

Twig, Gilad,Graf, Solomon A,Messerli, Mark A,Smith, Peter J S,Yoo, Seung H,Shirihai, Orian S American Physiological Society 2005 American journal of physiology. Cell physiology Vol.288 No.1

<P>Activation of the microglial neurotoxic response by components of the senile plaque plays a critical role in the pathophysiology of Alzheimer's disease (AD). Microglia induce neurodegeneration primarily by secreting nitric oxide (NO), tumor necrosis factor-alpha (TNFalpha), and hydrogen peroxide. Central to the activation of microglia is the membrane receptor CD40, which is the target of costimulators such as interferon-gamma (IFNgamma). Chromogranin A (CGA) is a recently identified endogenous component of the neurodegenerative plaques of AD and Parkinson's disease. CGA stimulates microglial secretion of NO and TNFalpha, resulting in both neuronal and microglial apoptosis. Using electrochemical recording from primary rat microglial cells in culture, we have shown in the present study that CGA alone induces a fast-initiating oxidative burst in microglia. We compared the potency of CGA with that of beta-amyloid (betaA) under identical conditions and found that CGA induces 5-7 times greater NO and TNFalpha secretion. Coapplication of CGA with betaA or with IFNgamma resulted in a synergistic effect on NO and TNFalpha secretion. CD40 expression was induced by CGA and was further increased when betaA or IFNgamma was added in combination. Tyrphostin A1 (TyrA1), which inhibits the CD40 cascade, exerted a dose-dependent inhibition of the CGA effect alone and in combination with IFNgamma and betaA. Furthermore, CGA-induced mitochondrial depolarization, which precedes microglial apoptosis, was fully blocked in the presence of TyrA1. Our results demonstrate the involvement of CGA with other components of the senile plaque and raise the possibility that a narrowly acting agent such as TyrA1 attenuates plaque formation.</P>

Magneto-roton excitation in a holographic quantum Hall fluid

Jokela, Niko,Lifschytz, Gilad,Lippert, Matthew Springer-Verlag 2011 Journal of high energy physics Vol.2011 No.2

Stability theorem of depolarizing channels for the minimal output quantum Rényi entropies

Bae, Eunok,Gour, Gilad,Lee, Soojoon,Park, Jeonghoon,Sanders, Barry C IOP 2016 JOURNAL OF PHYSICS A-MATHEMATICAL AND THEORETICAL Vol.49 No.11

<P>The stability theorem of the depolarizing channel states that if a state is close to achieving the minimal/maximal output value of a certain quantity through the channel, then it must be close to an input state giving the minimal/maximal value. We show that the stability theorem of the depolarizing channel holds for the output quantum <I>p</I>-Rényi entropy for <img SRC='http://ej.iop.org/images/1751-8121/49/11/115304/jpaaa110aieqn1.gif' ALIGN='MIDDLE' ALT='$p\geqslant 2$'/> or <I>p</I>?=?1, which is an extension of the known case <I>p</I>?=?2. As an application, we present a protocol in which Bob determines whether Alice prepares a pure quantum state close to a product state. In the protocol, Alice transmits to Bob multiple copies of a pure state through a depolarizing channel, and Bob estimates its output quantum <I>p</I>-Rényi entropy. By using our stability theorem, we show that Bob can determine whether her preparation is appropriate.</P>

Synthesis of Beta-glucan Nanoparticles for the Delivery of Single Strand DNA

황장선,이경우,Assaf A. Gilad,최종훈 한국생물공학회 2018 Biotechnology and Bioprocess Engineering Vol.23 No.2

The polysaccharide and biopolymer, beta-glucan, has been used for the purpose of enhancing immunity and its use as a drug delivery system has been diversified. Betaglucan, a triple helix structure, is unstructured to single strands by heat, DMSO or NaOH. Synthesis of beta-glucan nanoparticles using DMSO and water is easy and fast, but its size is limited. In this study, beta-glucan nanoparticles (GluNPs) were prepared by slicing beta-glucan into low molecular weight using various concentrations of Trifluoroacetic acid (TFA). TFA-treated GluNPs showed a minimum size of 250 nm. In addition, there is no abnormality in the characteristic of the functional groups of the nanoparticle surface after the acid treatment allowing GluNPs use in immune cell activation. Also, the efficiency of GluNPs as a drug or DNA carrier was confirmed by inserting ssDNA into the glucan triple helix structure. Beta-glucan nanoparticles developed in this study would be expected to be used for genetic material delivery and immune response enhancement.

Synthetic biological device: engineering of the electromagnetic perceptive gene for the external control of calcium ion transport into the cell

황장선,( Assaf A Gilad ),최종훈 한국공업화학회 2020 한국공업화학회 연구논문 초록집 Vol.2020 No.-

Developing synthetic biological devices to allow the noninvasive control of cell fate and function in vivo can potentially revolutionize the field of regenerative medicine. To address this unmet need, we designed an artificial biological “switch” that consists of two parts: (1) electromagnetic perceptive gene (EPG) and (2) magnetic particles. Our group has recently cloned the EPG from the Kryptopterus bicirrhis (glass catfish). The EPG encodes to a putative membrane-associated protein that responds to electromagnetic fields (EMF). This gene’s primary mechanism of action is to raise the intracellular calcium levels or change in flux through EMF stimulation. Here, we developed a system for the remote regulation of [Ca2+]i (i.e. intracellular calcium ion concentration) using streptavidin-coated ferromagnetic particles (FMPs) under a magnetic field. The results demonstrate that the EPG-FMPs can be used as a molecular calcium switch to express target proteins.

Alcohol Drinks Induce Acute Lowering in Circulating l-Arginine in Obese and Type 2 Diabetic Subjects

Assaf Buch,Tali Ganz,Julio Wainstein,Suzan Gilad,Rona Limor,Gabi Shefer,Mona Boaz,Naftali Stern 한국식품영양과학회 2022 Journal of medicinal food Vol.25 No.6

Since low serum l-arginine (Arg) and high asymmetric dimethylarginine (ADMA) can predict microvascular complications in type 2 diabetes mellitus (T2DM), we tested whether Arg and ADMA are affected by diet and physical activity in overweight/obese and T2DM subjects. We tested the effects on serum Arg and ADMA of single loads of dextrose, protein, fat, or alcohol (∼300 calories each); one episode of physical exercise; and 12 weeks of standard lifestyle modification (dietary and physical activity counseling). Alcohol drink was followed by ∼30% lowering in Arg. Arg and ADMA increased after a protein load but remained stable after glucose or fat load or 30 min of treadmill walk. Following 12 weeks of lifestyle modification, ADMA declined only in subjects achieving weight loss >5%. In conclusion, alcohol is a previously unrecognized acute suppressor of serum Arg. Lifestyle modification lowers ADMA in subjects who achieve weight loss >5%. Clinical Trial Registration Number: NCT04406402.

Functional bowel disorders among bariatric surgery candidates before and after surgery: A prospective cohort study

Sharif Yassin,Noa Sori,Ophir Gilad,Mati Shnell,Relly Richer,Nir Bar,Yishai Ron,Nathaniel Aviv Cohen,Subhi Abu-Abeid,Danit Dayan,Shai Meron Eldar,Shira Zelber-Sagi,Sigal Fishman 소화기인터벤션의학회 2024 International journal of gastrointestinal interven Vol.13 No.1

Background: Functional bowel disorders (FBDs), including irritable bowel syndrome (IBS), are common worldwide. Recently, increasingly many bariatric surgical procedures have been performed in response to rising obesity rates. However, data on the association between FBDs and bariatric surgery are scarce. We examined the prevalence of FBDs among candidates for bariatric surgery and prospectively investigated the association between FBDs and bariatric surgery. Methods: This prospective cohort study included 112 bariatric surgery candidates at the Tel Aviv Medical Center from 2019 to 2020. Before and after surgery, patients completed the Rome III questionnaire. Data regarding demographics, socioeconomic status, and gastrointestinal symptoms were recorded. The rates of FBDs—IBS, functional constipation (FC), functional diarrhea (FDi), and unspecified functional bowel disorder (UFBD)—were then compared from before surgery to 6 months after the procedure. Results: Of 112 candidates with obesity at baseline, 68 underwent surgery and completed the postoperative questionnaire. Overall, the respective prevalence rates of FBDs, IBS, FC, FDi, and UFBD were 37.5%, 2.7%, 17.9%, 5.4%, and 11.6%. Female sex and single status were particularly common among patients with FBDs, whereas divorced status was more frequent in the group without FBDs. However, these factors were not independently associated with FBD presence upon multivariable analysis. IBS was more prevalent after surgery than before (8.8% vs. 1.5%, P = 0.06), but FBDs in general did not share this trend (44.1% vs. 36.8%, P = 0.44). Conclusion: Bariatric surgery appears to increase the risk of developing IBS, while not impacting the overall risk of FBDs.

Shining flavor and radion phenomenology in warped extra dimension

Eshel, Yochay,Lee, Seung J.,Perez, Gilad,Soreq, Yotam Springer-Verlag 2011 Journal of high energy physics Vol.2011 No.10