Randomized, Double Blind, Placebo Controlled Study of Parallel Groups to Evaluate the Effect of Chronic Supplementation of L-arginine in the Muscular Performance.

The primary purpose of this study is to evaluate the effect of oral administration of L-arginine in the muscular fatigue of the quadriceps, expressed in terms of the Fatigue Resistance Factor (FRF). The secondary purpose of this study is to evaluate the effect of oral administration of L-arginine in the muscular force the quadriceps.

Start Date01 Oct 2008

Sponsor / Collaborator

Sanofi

100 Clinical Results associated with L-Arginine/L-Aspartate

100 Translational Medicine associated with L-Arginine/L-Aspartate

100 Patents (Medical) associated with L-Arginine/L-Aspartate

295

Literatures (Medical) associated with L-Arginine/L-Aspartate

01 Aug 2024·Journal of Pharmaceutical Sciences

Designing Robust Monoclonal Antibody Drug Products: Pitfalls of Simplistic Approaches for Stability Prediction

Article

Author: Gokarn, Yatin R ; Saluja, Atul ; Rembert, Kelvin B

Thermal stability attributes including unfolding onset (T_onset) and mid-point (T_m) are often utilized for efficient development of monoclonal antibody (mAb) products during lead selection and formulation screening workflows. An assumption of direct correlation between thermal and kinetic physical stability underpins this basic approach. While literature reports have substantiated this general approach under specific conditions, clear exceptions have been highlighted alongside. Herein, a set of mAbs formulated under diverse solution conditions to generate a broad array of thermal and kinetic stability profiles were systematically analyzed. Sequence modifications in the Fc region were purposefully engineered to generate a set of low-melting mAbs. A diverse set of excipients were subsequently utilized and shown to modulate the T_m over a wide range. While a general correlation between high T_m and low aggregation rate was observed under accelerated conditions, the predictive utility of T_m under relevant product storage conditions was inadequate at best. Critically, T_m data did not correlate with long-term aggregation rates under refrigerated or room temperature conditions. Even under accelerated conditions, T_m appeared to be a poor predictor of aggregation once it exceeded the solution storage temperature (40°C) by ∼15°C, similar to conditions routinely encountered in the development of canonical mAbs (T_m > 60°C). Pitfalls of simplistic correlative approaches are discussed in the context of practical biologics product development.

01 Aug 2024·Nature Structural & Molecular Biology

Mechanism of autocatalytic activation during proteasome assembly

Article

Author: Adams, Lea ; Huang, Lan ; Perez, Erignacio Fermin ; Blickling, Marie ; Razi, Aida ; Rajakumar, Tamayanthi ; Jiao, Fenglong ; Fung, Darlene ; Walsh, Richard M ; Rawson, Shaun ; Hanna, John ; Velez, Benjamin

Many large molecular machines are too elaborate to assemble spontaneously and are built through ordered pathways orchestrated by dedicated chaperones. During assembly of the core particle (CP) of the proteasome, where protein degradation occurs, its six active sites are simultaneously activated via cleavage of N-terminal propeptides. Such activation is autocatalytic and coupled to fusion of two half-CP intermediates, which protects cells by preventing activation until enclosure of the active sites within the CP interior. Here we uncover key mechanistic aspects of autocatalytic activation, which proceeds through alignment of the β5 and β2 catalytic triad residues, respectively, with these triads being misaligned before fusion. This mechanism contrasts with most other zymogens, in which catalytic centers are preformed. Our data also clarify the mechanism by which individual subunits can be added in a precise, temporally ordered manner. This work informs two decades-old mysteries in the proteasome field, with broader implications for protease biology and multisubunit complex assembly.

01 Apr 2024·Biomaterials Advances

Co-release of nitric oxide and L-arginine from poly (β-amino ester)-based adhesive reprogram macrophages for accelerated wound healing and angiogenesis in vitro and in vivo

Article

Author: Kharazi, Anousheh Zargar ; Javanmard, Shaghayegh Haghjooy ; Varshosaz, Jaleh ; Heydari, Parisa ; Kharaziha, Mahshid

Recently, insufficient angiogenesis and prolonged inflammation are crucial challenges of chronic skin wound healing. The sustained release of L-Arginine (L-Arg) and nitric oxide (NO) production can control immune responses, improve angiogenesis, enhance re-epithelialization, and accelerate wound healing. Here, we aim to improve wound healing via the controlled release of NO and L-Arg from poly (β-amino ester) (PβAE). In this regard, PβAE is functionalized with methacrylate poly-L-Arg (PAMA), and the role of PAMA content (50, 66, and 75 wt%) on the adhesive properties, L-Arg, and NO release, as well as collagen deposition, inflammatory responses, and angiogenesis, is investigated in vitro and in vivo. Results show that the PAMA/ PβAE could provide suitable adhesive strength (~25 kPa) for wound healing application. In addition, increasing the PAMA content from 50 to 75 wt% results in an increased release of L-Arg (approximately 1.4-1.7 times) and enhanced NO production (approximately 2 times), promoting skin cell proliferation and migration. The in vitro studies also show that compared to PβAE hydrogel, incorporation of 66 wt% PAMA (PAMA 66 sample) reveals superior collagen I synthesis (~ 3-4 times) of fibroblasts, controlled pro-inflammatory and improved anti-inflammatory cytokines secretion of macrophages, and accelerated angiogenesis (~1.5-2 times). In vivo studies in a rat model with a full-thickness skin defect also demonstrate the PAMA66 sample could accelerate wound healing (~98 %) and angiogenesis, compared to control (untreated wound) and Tegaderm™ commercial wound dressing. In summary, the engineered multifunctional PAMA functionalized PβAE hydrogel with desired NO and L-Arg release, and adhesive properties can potentially reprogram macrophages and accelerate skin healing for chronic wound healing.

100 Deals associated with L-Arginine/L-Aspartate

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Inflammation	Phase 3	Ukraine	Ukrainian Medical Stomatological Academy	20 Oct 2017
Periodontitis	Phase 3	Ukraine	Ukrainian Medical Stomatological Academy	20 Oct 2017

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ESC2018	Not Applicable	Metabolic Syndrome	62	L-Arginine aspartate	qryecmmznw(pqeqxfmbyz) = yomwqzkyzz bclxpuhedd (osdumqlcxd ) View more	-	26 Aug 2018
				l-arginine aspartate	qryecmmznw(pqeqxfmbyz) = qhxverktpg bclxpuhedd (osdumqlcxd ) View more
EULAR2015	Not Applicable	Rheumatoid Arthritis \| Hypertension	42	L-Arginine aspartate + standard treatment	(qxnywyomvo) = cwkpucycvf pvhunaujzn (qzxpgunyrp )	Positive	10 Jun 2015
				Standard treatment	(qxnywyomvo) = pdbgsvqjdo pvhunaujzn (qzxpgunyrp )
FP098 (ERA2015)	Not Applicable	Renal Insufficiency \| Rheumatoid Arthritis \| Hypertension	27	L-Arginine aspartate 30 ml/day	(lfibuylauw) = egzbbephtf ydxyoeeztt (qipvkobepr ) View more	Positive	21 May 2015
				Standard treatment	(lfibuylauw) = uguucuyaqw ydxyoeeztt (qipvkobepr ) View more
EULAR2011	Not Applicable	Rheumatoid Arthritis	40	Methotrexatum	yrtqlkxrjd(oekrymqzbb) = tjdjsetxew wygqebofwl (vthtafgoav ) View more	Positive	25 May 2011
				NO-donators (Arginine hydrochloride and L-Arginine aspartate)	yrtqlkxrjd(oekrymqzbb) = okjimjecxe wygqebofwl (vthtafgoav )

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