Primary hyperoxaluria is an inborn error of metabolism that results in marked overproduction of oxalate by the liver. The excess oxalate causes kidney failure and can cause severe systemic disease due to oxalate deposition in multiple body tissues.
Metabolic pathways that lead to oxalate are poorly understood, but recent evidence suggests that hydroxyproline may play a role. Sources of hydroxyproline include the diet and bone turnover. If hydroxyproline can be confirmed as a significant factor in primary hyperoxaluria, diet modification might be of value in reducing the severity of disease.
This protocol, in which hydroxyproline labelled with a cold isotope is infused intravenously in patients with primary hyperoxaluria, will allow the researchers to measure the amount of oxalate produced from hydroxyproline. The contribution of hydroxyproline metabolism to the amount of oxalate excreted in urine in will be able to be determined for patients with each of the known types of primary hyperoxaluria.

Start Date01 Sep 2013

Sponsor / Collaborator

Mayo Clinic

[+2]

100 Clinical Results associated with Hydroxyproline

100 Translational Medicine associated with Hydroxyproline

100 Patents (Medical) associated with Hydroxyproline

Literatures (Medical) associated with Hydroxyproline

01 Sep 2016·PainQ1 · MEDICINE

Group II mGluRs suppress hyperexcitability in mouse and human nociceptors

Q1 · MEDICINE

Article

Author: Price, Theodore J ; Schmidt, Robert E ; Vogt, Sherri K ; Davidson, Steve ; Valtcheva, Manouela V ; Golden, Judith P ; Ray, Pradipta R ; Gereau, Robert W ; Copits, Bryan A ; Ghetti, Andrea

AbstractWe introduce a strategy for preclinical research wherein promising targets for analgesia are tested in rodent and subsequently validated in human sensory neurons. We evaluate group II metabotropic glutamate receptors, the activation of which is efficacious in rodent models of pain. Immunohistochemical analysis showed positive immunoreactivity for mGlu2 in rodent dorsal root ganglia (DRG), peripheral fibers in skin, and central labeling in the spinal dorsal horn. We also found mGlu2-positive immunoreactivity in human neonatal and adult DRG. RNA-seq analysis of mouse and human DRG revealed a comparative expression profile between species for group II mGluRs and for opioid receptors. In rodent sensory neurons under basal conditions, activation of group II mGluRs with a selective group II agonist produced no changes to membrane excitability. However, membrane hyperexcitability in sensory neurons exposed to the inflammatory mediator prostaglandin E2 (PGE2) was prevented by (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC). In human sensory neurons from donors without a history of chronic pain, we show that PGE2 produced hyperexcitability that was similarly blocked by group II mGluR activation. These results reveal a mechanism for peripheral analgesia likely shared by mice and humans and demonstrate a translational research strategy to improve preclinical validation of novel analgesics using cultured human sensory neurons.

01 Sep 2015·Journal of Dermatological ScienceQ2 · MEDICINE

(2R/S,4R)-2-(2,4-Dihydroxyphenyl)thiazolidine-4-carboxylic acid prevents UV-induced wrinkle formation through inhibiting NF-κB-mediated inflammation

Q2 · MEDICINE

Letter

Author: Han, Yu Kyeong ; Lee, Eun Kyeong ; Ha, Young Mi ; Lee, Bonggi ; Kim, Dae Hyun ; An, Hye Jin ; Moon, Hyung Ryong ; Chung, Hae Young ; Chun, Pusoon ; Chung, Ki Wung ; Son, Sujin ; Moon, Kyoung Mi ; Yun, Hwi Young ; Ullah, Sultan

This study examined inhibitory effects of (2R/S,4R)-2-(2,4-dihydroxyphenyl)thiazolidine-4-carboxylic acid on wrinkle formation using Hs27 human dermal fibroblasts and HR-1 hairless mouse.In this study Hs27 human dermal fibroblasts were pretreated with MHY384 followed by UVA exposure and type 1 procollagen concentration in culture medium was measured using an ELISA kit.This study resulted that, (2R/S,4R)-2-(2,4-Dihydroxyphenyl)thiazolidine-4-carboxylic acid prevented UV-induced wrinkle formation through inhibiting NF-κB-mediated inflammation using Hs27 human dermal fibroblasts and HR-1 hairless mouse.This study concluded that MHY384 could be potentially used to prevent wrinkle formation and would be a novel additive for anti-aging cosmetics.

01 Jun 2015·Urolithiasis

A single-blind, parallel trial of l-hydroxyproline in healthy adult subjects

Letter

Author: Ayako Kamimura ; Haruo Ito ; Koji Morishita ; Saori Akiduki

As calcium oxalate is the most common constituent of urinary stones animal model of the urolithiasis has been established by feeding l-hydroxyproline, an endogenous precursor of oxalate. However, the influence of oral l-hydroxyproline on human urinary oxalate excretion has not been clearly demonstrated. We herein report a clinical study examining the influence of daily ingestion of l-hydroxyproline on urinary oxalate levels with a focus on measuring oxalic acid excreted in the urine. In detail, we performed a single-blind, parallel designed study at Sta. Rosa Hospital and Medical Center, Philippines. This study was approved by the hospital review board and was in compliance with the Declaration of Helsinki. Forty healthy subjects (20 males and 20 females, 33.4 ± 9.4 years of age, who has no history of kidney disease) were divided into 4 groups with 10 subjects in each group with same sex ratio. l-Hydroxyproline doses of 0, 500, 1000 and 2000 mg were taken daily after breakfast for 12 weeks. Prior to and during each scheduled examination, subjects were reminded to refrain from intake of oxalate-rich foods and to drink more than 1 L of water per day. Medical interviews, physical examinations, vital sign measurements, anthropometric measurements, blood examinations and 24-h urine sample collections were conducted every 4 weeks at the hospital. A male and two female subjects were withdrawn from this study because of pregnancy or urinary tract infection so the final number of subjects was 37. Informed consent was obtained from qualified individuals. The baseline characteristics of subjects of each group were not different statistically. No adverse events were observed throughout the trial period except for a few symptoms like itchiness or headache which were self-reported from subjects, but the relationships with the test material were denied by the principle investigator. On the 24-h urine test, almost no markers changed, but there was a significant change in total l-hydroxyproline excretions in the 2000 mg l-hydroxyproline group compared to control group at the point of 8 weeks after first intake. Moreover, oxalic acid levels also increased significantly in the 2000 mg group at the point of 8 and 12 weeks after first intake. However, all values returned to basal values after 4 weeks from the last l-hydroxyproline intake (Table 1). Various dietary factors can change urine oxalate excretion; one is a high-protein diet. Many studies have addressed urinary oxalate excretion after high-protein intake, but conclusions are still uncertain. For example, Knight et al. [1] not only showed significant changes in urinary oxalate with 5 and 10 g of gelatine administered to healthy subjects, but also indicated that the high-protein diet did not influence total daily urinary oxalate excretion [2]. Collagen contains approximately 10 % of l-hydroxyproline, and the daily turnover of collagen in humans is estimated to be 2–3 g/day so the metabolism of l-hydroxyproline will be 240–420 mg [1]. In this study, the urinary oxalate level following 500 or 1000 mg/day l-hydroxyproline ingestion did not change compared with control but 2000 mg/day l-hydroxyproline ingestion increased the urinary oxalate excretion, but the values did not exceed the level of stone forming individuals with a mean oxalate excretion 40 mg/day [2]. As noted, there are various opinions on the association of dietary and urinary oxalate. Recently, it was reported that the Dietary-Approaches to Stop Hypertension (DASH)-style diet is more effective in reducing calcium oxalate supersaturation than a low-oxalate diet, although it includes a lot of fruits and vegetables which contain much oxalate [3]. Thus, the influence of the diet in conjunction with oxalate is still unclear in human metabolism. Moreover, we found no accumulation of l-hydroxyproline and oxalate in the withdrawal period same as the animal model. The metabolic significance of l-hydroxyproline is still unclear and further investigation is warranted. Table 1 Urinalysis results of 24-h urine sample

100 Deals associated with Hydroxyproline

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Indication	Highest Phase	Country/Location	Organization	Date
Hyperoxaluria, Primary	Phase 2	US	National Institutes of Health	30 Sep 2013
Nephrocalcinosis	Phase 2	US	National Institutes of Health	30 Sep 2013
Nephrolithiasis, Calcium Oxalate	Phase 2	US	National Institutes of Health	30 Sep 2013

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASN2014	Not Applicable	Hyperoxaluria	-	Hydroxyproline	(rqwoolbjfp) = glinntkjca giwmxspfuf (hitmesstbn, 11) View more	Positive	11 Nov 2014
ASN2012	Not Applicable	-	4	Hydroxyproline	dvsufvgnow(lmiklfulmn) = byfwhekptw awvggznxdv (ukmsgmyosj, 3.7) View more	-	30 Oct 2012
2073 (AUA2012)	Not Applicable	Nephrolithiasis	8	DIETARY HYDROXYPROLINE (Control diet)	loxbaywkuk(xisubprxuk) = vrfhmepfje gjhkuyqvnz (pmmtbhzzoj )	-	01 Apr 2012
2073 (AUA2012)	Not Applicable	Nephrolithiasis	8	DIETARY HYDROXYPROLINE (10% hydroxyproline diet)	loxbaywkuk(xisubprxuk) = gbmnsoxhec gjhkuyqvnz (pmmtbhzzoj )	-	01 Apr 2012

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