The aging population is growing rapidly. For the first time ever, Canadian seniors outnumbered young adults in 2016. Aging is associated with many physical and metabolic deteriorations including the loss of muscle mass and strength, insulin resistance, increased inflammation and oxidative stress.
The muscles of our bodies are composed of proteins and proteins are made of small building blocks called amino acids. Our bodies have the ability to make some amino acids which are called the non-essential amino acids. However, there are certain amino acids that our body's need to make protein but can only be supplied from the foods that we consume. These are called essential amino acids. Tryptophan is one of the essential amino acids that the body needs. Tryptophan is required for protein synthesis and acts as a precursor for serotonin and nicotinic acid. Therefore, there may be a need for more threonine in the diet of older adults. However, the current requirement for threonine is based on studies conducted exclusively in young adults. Thus, the purpose of this study is to find out how much tryptophan older adults need.

Start Date01 Jun 2024

Sponsor / Collaborator

The Hospital for Sick Children

[+1]

ChiCTR2400081970 / RecruitingNot ApplicableIIT

Study of csDMARDs combined with L-tryptophan supplementation (L-Tryptophan) in the treatment of rheumatoid arthritis

Start Date13 Nov 2023

Sponsor / Collaborator-

DRKS00024510 / RecruitingNot ApplicableIIT

Atopic Dermatitis - novel functions of TRP channels in neuro immune interaction mechanism - TRP channels

Start Date01 Feb 2023

Sponsor / Collaborator-

100 Clinical Results associated with Tryptophan

100 Translational Medicine associated with Tryptophan

100 Patents (Medical) associated with Tryptophan

14,668

Literatures (Medical) associated with Tryptophan

01 Jun 2025·Neural Regeneration Research

Dip2a regulates stress susceptibility in the basolateral amygdala

Article

Author: He, Xiaoxiao ; Chai, Weitai ; Zhu, Xiaojuan ; He, Zixuan ; Tian, Meng ; Yu, Huali ; Li, Jing

JOURNAL/nrgr/04.03/01300535-202506000-00025/figure1/v/2024-08-08T040853Z/r/image-tiff Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A (Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid–associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.

01 Feb 2025·Talanta

Preparation of gelatine calibration standards for LA-ICP-MS bioimaging with 266 nm laser ablation systems

Article

Author: Bishop, David P ; Bordin, Dayanne C M ; Bordin, Dayanne C.M. ; Westerhausen, Mika T ; Lockwood, Thomas E. ; Bishop, David P. ; Westerhausen, Mika T. ; Lockwood, Thomas E

Gelatine is the external standard matrix of choice for quantitative biomaging of elements and metal tags in tissue. Its ablation characteristics closely match that of tissue when using 193 and 213 nm lasers, but this has not been demonstrated at 266 nm. With the interest in 266 nm laser ablation systems growing due to the selective ablation of tissue over glass substrates, this gap needed to be investigated. Optical profilometry was used to map the line crater volumes of gelatine and murine brain and quadriceps tissues ablated with a 266 nm laser. Raw gelatine did not ablate in a similar manner to either tissue type and ultra-violet absorbent chemical additives were required to match ablation volumes. Addition of either 4 g L^-1l-tryptophan or 3 g L^-1 gallic acid was used to match the ablation volume of murine quadriceps. Murine brain tissue had an increased ablation volume over the quadriceps tissue (1400 ± 130 versus 1100 ± 160 μm³ at 1.5 J cm^-2), and the addition of 5 g L^-1 gallic acid and the use of low laser energy (≤1.5 J cm^-2) was required to match the ablation of brain tissue. The modified standards were tested on a 213 nm laser, and the addition of either additive to gelatine did not affect ablation volume. The effect of additives on fractionation and two-phase sample transport was investigated, no fractionation was observed, and a decrease in two-phase sample transport of up to 60 % was obtained with the modified gelatine. This decrease was caused by the reduced laser energy required for ablation. Finally, the potential uses of optical profilometry as a standardisation tool are discussed.

01 Feb 2025·Food Hydrocolloids

Colloidal nanoparticles of a β-cyclodextrin/L-Tryptophan inclusion complex for use as Pickering emulsion stabilizers

Article

Author: Abbaspourrad, Alireza ; Wang, Junyi ; Khazdooz, Leila ; Uyar, Tamer ; Dong, Hongmin ; Dadmohammadi, Younas ; Zarei, Amin

Inclusion complexes of β-cyclodextrin (β-CD) and tryptophan (Trp) were synthesized using an antisolvent approach, and fully characterized. Scanning electron microscope images proved the formation of the β-CD/Trp NPs and the powder X-ray diffraction pattern indicated the formation of a crystalline channel-like structure for the β-CD/Trp nanoparticles (NPs). The NPs of a β-CD/Trp inclusion complex were used as a natural stabilizer at the oil/water interface of a Pickering emulsion. Pickering emulsions with an oil to water ratio of 1:1 (v:v) were obtained under high-speed homogenization and different mass ratios of the β-CD to Trp (1:0, 1:0.1, 1:0.25, 1:0.5, 1:1), and at different pH levels (3, 5, 7, 9). At pH 9, when the β-CD:Trp mass ratio was 1:0.1, the β-CD/Trp NPs were hydrophilic, and the oil-in-water Pickering emulsions stabilized by those nanoparticles showed the highest storage stability: 180 days at room temperature. In contrast, when the emulsions were prepared at pH 5 with the weight ratios of either 1:0.1 or 1:1, β-CD:Trp, the nanoparticles were hydrophobic and could be used to stabilize water-in-oil Pickering emulsions.

News (Medical) associated with Tryptophan

29 Jul 2024

·www.prnewswire.com

HKBU develops new approach for accurate and efficient inspection of sulfur-treated food and Chinese herbal medicines

HONG KONG, July 29, 2024 /PRNewswire/ -- A research team at Hong Kong Baptist University (HKBU) has developed a new approach for the inspection of sulfur-treated food and Chinese herbal medicinal products through a new chemical marker called tryptophan sulfonate. This approach is more accurate, rapid and efficient for large sample quantities compared to the current testing method. The study marks a potential advancement in food safety and quality assurance, providing the industry with a robust tool for inspecting sulfur-treated food and Chinese herbal medicinal products. Continue Reading Dr Xu Jun, Assistant Professor of the Teaching and Research Division of the School of Chinese Medicine (left), and Mr Chan Kam-chun, Senior Research Assistant of HKBU (right), have developed a tryptophan sulfonate test which can inspect sulfur-treated food and Chinese herbal medicine more accurately and rapidly. The research findings have been published in the international scientific journal Food Chemistry. More accurate and efficient test in need Sulfur treatment, including sulfur fumigation and the addition of sulfites, is a common preservation method employed in the food and Chinese herbal medicinal industries. However, excessive consumption of preservative sulfites in food and Chinese herbal medicinal products can lead to respiratory symptoms and compromised nutritional value and safety. Currently, sulfite test is the most commonly used method for inspecting residual sulfites in sulfur-treated food. Nevertheless, sulfites are chemically unstable, sometimes leading to inaccurate results. Sulfite test is also labour-intensive and time consuming. It can only analyse one sample at a time, making high-throughput analysis challenging. Furthermore, sulfite test may yield false-positive results for food rich in endogenous sulfur-containing components such as garlic and onion. Tryptophan sulfonate as a chemical marker In search of a more accurate and efficient testing approach, Dr Xu Jun , Assistant Professor of the Teaching and Research Division of the School of Chinese Medicine at HKBU, and his research team identified a chemical compound called tryptophan sulfonate in sulfur-fumigated samples using untargeted metabolomics. Tryptophan sulfonate is formed when tryptophan, a naturally occurring amino acid in many foods, reacts with sulfite. The research team conducted comparative experiments on 20 food products using the tryptophan sulfonate test. It was found that tryptophan sulfonate is present consistently in all sulfur-fumigated food samples but not in non-fumigated samples. The finding demonstrated the potential of tryptophan sulfonate as a specific chemical marker for distinguishing sulfur-treated and non-sulfur-treated food products. Tryptophan sulfonate test outperforms sulfite test To evaluate the applicability of tryptophan sulfonate in the inspection of sulfur-treated food products and Chinese herbal medicines, the team applied tryptophan sulfonate and sulfite tests to 50 food and Chinese herbal medicinesamples collected from markets. It was found that tryptophan sulfonate test and sulfite test results were mostly identical except for six food samples, including corn starch, dried star fruit, dried mango, snow fungus, garlic and onion. The tryptophan sulfonate test result was positive in corn starch, dried star fruit, dried mango and snow fungus, but negative in garlic and onion; sulfite test yielded opposite results. As garlic and onion are known to contain endogenous sulfur-containing components, it is evident that the positive sulfite test result is not a consequence of sulfur-treatment. Tryptophan sulfonate test is therefore a more reliable approach for detecting sulfur-treatment for food items with intrinsic sulfur-containing constituents. False-negative due to instability of sulfites For the discrepancies between the two tests on the other four food samples, the research team hypothesised that the sulfite test may produce false-negative results due to the instability of sulfites caused by high temperature and prolonged storage of the food samples. In a separate experiment, the research team found that sulfite levels in sulfur-fumigated ginger, yam and ginseng declined by around 90% to 100% after nine months of storage, and reduced by around 50% to 72% after heating, while the tryptophan sulfonate levels remained stable. They concluded that the instability of residual sulfites could lead to false-negative results. In contrast, tryptophan sulfonate exhibited greater stability over heat and storage, suggesting it serves as a better chemical marker for sulfur-treatment inspection. High throughput screening made possible On the testing procedure, tryptophan sulfonate test is faster and more automated. It involves a direct ultrasonic extraction for one hour and mass spectrometry analysis for two minutes, allowing the parallel handling of batches of samples. In contrast, sulfite test requires 2.5 hours of manual operation, including reflux extraction and titration for a single sample test. Dr Xu Jun said: "Our research showed that tryptophan sulfonate serves as a highly distinctive chemical marker, enhancing the accuracy and efficiency of sulfur-treated food and Chinese herbal medicine inspection. It is especially suitable for high throughput screening of large samples size. It demonstrates the potential in offering a more cost-effective alternative for the existing test protocol adopted by the industry." Moving forward, the research team hopes to further develop the tryptophan sulfonate test for commercial application. SOURCE Hong Kong Baptist University

Clinical ResultDiagnostic Reagents

02 Jul 2024

·www.prnewswire.com

Pet Calming Chews Result in Human Panic

Common July 4 Pet Anxiety Treatment Leads to Accidental Overdose MINNEAPOLIS, July 2, 2024 /PRNewswire/ -- Many people use calming chews to relieve their pet's anxiety, especially during the July 4 holiday. Not only can the sound of fireworks scare your pet, but a change in routine or sudden influx of visitors can cause pets great distress. While these supplements can help calm your pet, they can also be dangerous if taken in too great of a quantity. Continue Reading It was anything but relaxing when Elton overdosed on calming chews and had to be rushed to the veterinary hospital for treatment. "I had just moved to a new apartment, and I ran out to do some grocery shopping," explained Jacque Dickson, who lives with her dogs Elton and Chubbs in Greensboro, North Carolina. "My father had recently bought a bottle of calming chews for Chubbs, who can be anxious. The bottle was in an unopened box, but the dogs managed to get into it and consume the entire bottle of more than 160 chews. My first call was to the pet emergency room, and they had me call Pet Poison Helpline before I even left the house." By calling first, the toxicology experts at Pet Poison Helpline were able to start developing a recommended treatment plan based on Elton and Chubbs' individual situations that could be ready when Dickson arrived at the clinic. "After talking with the experts at Pet Poison Helpline, they determined that Chubbs was not in danger because of his size," Dickson explained. "He's a fit cattle dog, but he's 65 pounds. Because Elton is only 10 pounds, they recommended I take him into the hospital for treatment and observation." As soon as Dickson arrived at Carolina Veterinary Specialists in Greensboro, the medical team was ready to start treatment. The Pet Poison Helpline team had determined that Elton had consumed a dangerous level of the product, which contains tryptophan. The toxicologists were concerned with Elton developing hypernatremia due to the number of chews he ingested, potentially causing a fluid shift that results in increased sodium concentrations. There was also a concern for serotonin syndrome to develop, which causes numerous neurologic and cardiovascular signs, due to the amount of L-tryptophan ingested. With this in mind, the specialists at Pet Poison Helpline recommended an antiemetic, electrolyte monitoring, intravenous fluids and monitoring for serotonin syndrome, a condition that happens when there is too much serotonin in the body. "The dedicated team at Carolina Veterinary Specialists took great care of Elton," said Dr. Renee Schmid, a senior veterinary toxicologist and director of Veterinary Medicine at Pet Poison Helpline. "He was closely monitored overnight and went home the next day, where Ms. Dickson could monitor both him and Chubbs for any additional symptoms or changes in behavior." Accidental medication poisoning is only one of the risks facing pets during the July 4 holiday. An even greater threat is pets being terrified by the loud fireworks explosions or getting out of the house and into other dangers such as being hit by a car. Pet Poison Helpline has partnered with AKC Reunite, the nation's largest not for profit pet recovery service, offering its 24/7 toxicology expertise as an optional, unlimited benefit for its members to add to their pet's lifetime protection. "According to AKC Reunite, more pets go missing during the July 4th weekend than any other time of the year," said Dr. Schmid. "To help prevent problems with your pet, AKC Reunite has six tips for protecting your pet this Independence Day." Tip 1: Establish a Place of Sanctuary Make sure your dog or cat always has access to a comfortable, quiet and safe place to get away from the noise. Either a closet, under a piece of furniture or in his crate. Tip 2: Make Toys and Long-Lasting Treats Available Keep toys and long-lasting treats in your pet's safe area to make the area more fun and to provide distractions from loud noises and flashes. Tip 3: Exercise Earlier in the Day is Key Make time to exercise your pet during daylight hours; then, keep them safely indoors before the fireworks begin. Tip 4: Turn Up the Music, but Not Too Loud At dusk, close your windows and curtains and turn on music or the television to muffle the loud noises that accompany social gatherings and the booming thunder from fireworks. Tip 5: Watch Their Body Language: Pets convey fear by shivering, cowering, tucking their tail between the legs, and averting their eyes. Looming over a fearful dog will only make it more anxious; and unless a dog is likely to get hurt it is often best to leave a fearful dog alone because its behavior when scared is uncertain. Overall, you know your pet best, and recognizing the cues they give you through their body language will help to determine the best way to make them as comfortable as possible. "Enjoy the July 4th festivities with your family and friends, but don't forget about your furry loved ones," Dr. Schmid said. "Taking a few precautions can help protect your pet from a variety of dangers." Pet Poison Helpline created Toxin Tails to educate the veterinary community and pet lovers on the many types of poisoning dangers facing pets, both in and out of the home. All the pets highlighted in Toxin Tails have been successfully treated for the poisoning and fully recovered. About Pet Poison Helpline Pet Poison Helpline®, your trusted source for toxicology and pet health advice in times of potential emergency, is available 24 hours, seven days a week for pet owners and veterinary professionals who require assistance treating a potentially poisoned pet. We are an independent, nationally recognized animal poison control center triple licensed by the Boards of Veterinary Medicine, Medicine and Pharmacy providing unmatched professional leadership and expertise. Our veterinarians and board-certified toxicologists provide treatment advice for poisoning cases of all species, including dogs, cats, birds, small mammals, large animals and exotic species. As the most cost-effective option for animal poison control care, Pet Poison Helpline's fee of $85 per incident includes follow-up consultations for the duration of the case. Based in Minneapolis, Pet Poison Helpline is available in North America by calling 800-213-6680. Additional information can be found online at . Contact: Dr. Renee Schmid Pet Poison Helpline® (952) 806-3803 [email protected] SOURCE Pet Poison Helpline

26 Mar 2024

·www.prnewswire.com

CV Sciences, Inc. Expands +PlusCBD Pet Product Offerings with the Launch of Pet Chews

Pet Hip and Joint Health Chews and Pet Calming Care Chews improve the physical and emotional well-being of dogs SAN DIEGO, March 26, 2024 /PRNewswire/ -- CV Sciences, Inc. (OTCQB: CVSI) (the "Company", "CV Sciences", "our", "us" or "we"), a preeminent consumer wellness company specializing in hemp extracts and other proven, science-backed natural ingredients and products, proudly announces its latest innovation and product launch: a premier CBD chew tailored for pets, +PlusCBD™ Pet Hip and Joint Health Chews and +PlusCBD™ Pet Calming Care Chews. +PlusCBD™Pet wellness treats are crafted with the utmost care and supported by extensive research, and are now further validated by a landmark safety study backed by the National Animal Supplement Council (NASC). NASC is the leading trade association advocating for the health and wellness of companion animals that are given health supplements by their owners. The latest additions to the industry-leading +PlusCBD lineup are now available nationwide at select retailers and from our website at . Continue Reading Pet Chews Available Now! The pet wellness industry has witnessed a growing demand for natural alternatives to support pets' overall well-being. In response to this need, +PlusCBD™Pet has developed a premium CBD chew with the mission of providing the highest quality ingredients and best-in-class health and nutrition for cherished family members - our pets. These formulas utilize the therapeutic properties of cannabidiol (CBD) derived from organic hemp plants. Along with CBD, our chews incorporate a curated selection of antioxidants, anti-inflammatory agents, and vital supplements designed to enhance the well-being of your loving companion. While one in five dogs deal with joint pain, +PlusCBD Pet Hip and Joint Health Chews pairs premium THC-free hemp extract with Glucosamine, Turmeric, Rosehips, and Ginger Root providing relief for pets grappling with age-related stiffness or discomfort from physical activity. Similarly, more than 70% of dogs exhibit at least one anxiety-related behavior or habit. The non-GMO, THC-free +PlusCBD Pet Calming Care Chew employs a vitamin-rich formula of Chamomile, L-Tryptophan, Ginger Root, and L-Theanine, offering respite from anxiety and stress triggered by various stimuli such as separation, loud noises, or environmental changes, fostering a sense of relaxation and well-being in your devoted pet. Each CBD chew undergoes rigorous testing by independent laboratories to ensure purity, potency, and compliance with NASC's stringent quality standards. With a THC-free formulation and non-psychoactive properties, our chews offer a safe and effective solution for pet owners seeking natural alternatives for their companions. Joseph Dowling, CEO of CV Sciences, commented on the significance of the NASC safety study, stating, "The NASC's comprehensive safety study further validates CBD supplements to promote the health and wellness of our family pets. Our long-standing commitment to quality and safety will provide pet owners with products they can trust. We are immensely proud to offer CBD chews that not only meet our rigorous standards, but also exceed industry benchmarks for safety and efficacy." +PlusCBD™ Pet Hip and Joint Health Chews and Pet Calming Care Chews are the first new offerings from CV Sciences in 2024. In 2023, the award-winning wellness brand introduced several product offerings designed to elevate the health and well-being of our human consumers, including +PlusCBD™ Reserve Collection Extra Gummies, +PlusCBD™ Reserve Collection Sleep Gummies, +PlusCBD™ Daily Balance THC-Free Gummies and Softgels and +PlusCBD™ Reserve Collection Softgels. The continued expansion of the Company's industry-leading product catalog amplifies its commitment to providing all users, both two-legged and four, with research-supported, plant-based health and wellness alternatives. For more information, please visit +PlusCBD or CV Sciences. About CV Sciences, Inc. CV Sciences, Inc. (OTCQB:CVSI) is a consumer wellness company specializing in nutraceuticals and plant-based foods. The Company's hemp extracts and other proven, science-backed, natural ingredients and products are sold through a range of sales channels from B2B to B2C. The Company's +PlusCBD™ branded products are sold at select retail locations throughout the U.S. and are the top-selling brands of hemp extracts in the natural products market, according to SPINS, the leading provider of syndicated data and insights for the natural, organic and specialty products industry. With a commitment to science, +PlusCBD™ product benefits in healthy people are supported by human clinical research data, in addition to three published clinical case studies available on PubMed.gov. +PlusCBD™ was the first hemp extract supplement brand to invest in the scientific evidence necessary to receive self-affirmed Generally Recognized as Safe (GRAS) status. The Company's Cultured Foods™ brand provides a variety of 100% plant-based food products. Committed to crafting nutritious and flavorful alternatives, Cultured Foods™ caters to individuals seeking vegan, gluten-free, or flexitarian options for a wholesome and satisfying culinary experience. CV Sciences, Inc. has primary offices and facilities in San Diego, California, and Warsaw, Poland. The Company also operates a drug development program focused on developing and commercializing CBD-based novel therapeutics. Additional information is available from OTCMarkets.com or by visiting . Media Contact: Alexis Isaacs [email protected] SOURCE CV Sciences, Inc.

100 Deals associated with Tryptophan

External Link

KEGG	Wiki	ATC	Drug Bank
D00020	Tryptophan	N06AX02	DB00150

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Depressive Disorder	-	-	-

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Progressive pulmonary fibrosis	Phase 2	CN	Shanxi Bethune Hospital	01 Mar 2024

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ESMO2022	Not Applicable	Non-Small Cell Lung Cancer	14	Taxol-ramucirumab-pembrolizumab (TRP)	rpfbijhrpv(qcyrcvjvrt) = 1 patient developed G3 immune-mediated diarrhea gzjvktbopc (zxlbxpiqhi ) View more	-	10 Sep 2022
ARVO2019	Phase 2	Macular Edema	40	Monthly 0.5 mg intravitreal ranibizumab injections	(fcxnaxfjdz) = obbgjrspmq zzhgihosvb (jjcqbsfscs )	-	01 Jul 2019
ARVO2019	Phase 2	Macular Edema	40	Monthly 0.5 mg ranibizumab plus TRP	(fcxnaxfjdz) = rsgykyspoe zzhgihosvb (jjcqbsfscs )	-	01 Jul 2019
IEC2019	Not Applicable	Epilepsy TRP metabolism \| astrocytic function	-	Abnormal Tryptophan Metabolism (Standard diet)	uzrjqrxvlm(bkddlitppq) = decreased by TRP loading in ddY mice ooscugxizt (kseobshkzo ) View more	Positive	24 Jun 2019
NCT00865202 (CTgov)	Phase 3	Emergence Delirium	301	placebo+L-tryptophan supplementation	mhqdadissr(haaagjpcpe) = bbprtngaon vnkepuqjca (fxvbwmfdah, jtaujkhzic - mcvpbpkihd) View more	-	01 Jun 2017
ERA2017	Not Applicable	Renal transplant rejection plasma TRP \| plasma KYN \| IDO-activity	695	TRYPTOPHAN	ytslljpksd(whxofkvosn) = aioaiziqna gcxrpspljn (ojqoxfqvxf, 2.3 - 5.5) View more	Positive	26 May 2017
ERA2017	Not Applicable		695	TRYPTOPHAN	ytslljpksd(whxofkvosn) = ftiibwwows gcxrpspljn (ojqoxfqvxf, 1.7 - 2.3) View more	Positive	26 May 2017
not available (ASN2013)	Not Applicable	tryptophan \| kynurenine	30	Tryptophan	wwloplzlkq(hsbqpyfbhu) = qdjqixbbhx oebtfrdqfn (veyggizzks ) View more	Negative	05 Nov 2013
ASN2013	Not Applicable	-	-	Tryptophan	cyimvyvnbl(eptybbcdac) = fjvytlbrdj txazqkyeer (khyjdkiyyw ) View more	-	05 Nov 2013
ASN2013	Not Applicable	-	-	Tryptophan	cyimvyvnbl(eptybbcdac) = lhpxbpcood txazqkyeer (khyjdkiyyw ) View more	-	05 Nov 2013

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