Novel Off-label Use of Desipramine in Infantile Neuroaxonal Dystrophy: Targeting the Sphingolipid Metabolism Pathway to Reduce Accumulation of Ceramide.

This is a research study to find out if clinically prescribed desipramine is effective at improving the symptoms and slowing the progression of Infantile Neuroaxonal Dystrophy (INAD) in affected children.
Participants will receive an initial oral dose of study drug once a day. This dose may be changed depending on response to study drug Clinically collected data will be recorded for up to 5 years. Investigators will also ask for participant permission to obtain a sample of child's skin biopsy from unused clinical sample previously collected for standard of care.

Start Date14 Jan 2019

Sponsor / Collaborator

Duke University

NCT03548454 / RecruitingPhase 4IIT

Comparing Effectiveness of Duloxetine and Desipramine in Patients With Chronic Pain: A Pragmatic Trial Using Point of Care Randomization

Over 100 million Americans suffer from chronic pain resulting in annual cost of roughly $635 billion. Limited treatments are available for this widespread disease. The data supporting these treatments lack generalizability to patients with more serious medical and psychological comorbidities who are often excluded from explanatory efficacy trials. Our work aims to integrate randomized comparative effectiveness research with patient care. The investigators will randomize the patients and collect data using an open-source learning healthcare system already in use in our department to monitor patients' progress: Collaborative Health Outcomes Information Registry (CHOIR). Collaborative Health Outcomes Information Registry uses the National Institute of Health Patient Reported Outcomes Measurement Information System item banks for comparative metrics through computer adaptive testing. The investigators will leverage the advantage of this novel system to compare effectiveness of duloxetine and desipramine in decreasing pain in patients with chronic pain. The investigators will also compare adherence of patients to these two commonly used medications over a period of six months. This will evaluate feasibility of integrating randomized comparative effectiveness research with patient care in subspecialty clinics. Collaborative Health Outcomes Information Registry can then be applied for numerous future trials to advance our knowledge in perioperative and pain medicine.

Start Date20 Sep 2018

Sponsor / Collaborator

Stanford University

IRCT20160813029315N2 / CompletedPhase 2/3IIT

Placebo-controlled randomized clinical trial testing the efficacy of desipramine in reducing craving in patients with methamphetamine use disorder

Start Date03 Jun 2016

Sponsor / Collaborator-

100 Clinical Results associated with Desipramine Hydrochloride

100 Translational Medicine associated with Desipramine Hydrochloride

100 Patents (Medical) associated with Desipramine Hydrochloride

7,308

Literatures (Medical) associated with Desipramine Hydrochloride

01 Dec 2024·PAIN

Nucleus accumbens myocyte enhancer factor 2C mediates the maintenance of peripheral nerve injury–induced physiological and behavioral maladaptations

Article

Author: Nestler, Eric J. ; Pryce, Kerri D. ; Karkhanis, Anushree N. ; Estill, Molly ; Serafini, Randal A. ; Shen, Li ; Farzinpour, Zahra ; Akbarian, Schahram ; Patel, Vishwendra ; Teague, Collin D. ; Kelley, Abigail M. ; Torres-Berrio, Angelica ; Zachariou, Venetia ; Blitzer, Robert D. ; Sakloth, Farhana

Abstract:

Preclinical and clinical work has demonstrated altered plasticity and activity in the nucleus accumbens (NAc) under chronic pain states, highlighting critical therapeutic avenues for the management of chronic pain conditions. In this study, we demonstrate that myocyte enhancer factor 2C (MEF2C), a master regulator of neuronal activity and plasticity, is repressed in NAc neurons after prolonged spared nerve injury (SNI). Viral-mediated overexpression of Mef2c in NAc neurons partially ameliorated sensory hypersensitivity and emotional behaviors in mice with SNI, while also altering transcriptional pathways associated with synaptic signaling. Mef2c overexpression also reversed SNI-induced potentiation of phasic dopamine release and neuronal hyperexcitability in the NAc. Transcriptional changes induced by Mef2c overexpression were different than those observed after desipramine treatment, suggesting a mechanism of action different from antidepressants. Overall, we show that interventions in MEF2C-regulated mechanisms in the NAc are sufficient to disrupt the maintenance of chronic pain states, providing potential new treatment avenues for neuropathic pain.

01 Dec 2024·VETERINARY JOURNAL

Imipramine in dogs: A pharmacokinetic study following oral administration under fasted and fed conditions

Article

Author: Čudina, N. ; Fadel, C ; Lisowski, A ; Serih, F ; Poapolathep, A ; Poapolathep, A. ; Lisowski, A. ; Serih, F. ; Čudina, N ; Giorgi, M. ; Fadel, C. ; Giorgi, M ; Łebkowska-Wieruszewskac, B. ; Łebkowska-Wieruszewskac, B

This study investigates the pharmacokinetics (PK) of imipramine, a tricyclic antidepressant used in human psychiatric disorders and increasingly considered in veterinary medicine. Despite its longstanding use in canines, prior research on imipramine's PK in dogs is lacking. This study aimed to determine the PK of imipramine in dogs in regards to feeding conditions, and to ascertain whether desipramine (active metabolite) is formed or not. In this study, six male Labrador dogs underwent oral administration (1.5 mg/kg) of imipramine tablets (10 mg each; Tofranil®, Novartis) in both fasted and fed conditions. Dogs were randomly allocated to one of two treatment groups, employing an open, single-dose, two-treatment, two-phase, cross-over design, with a washout period of one week. Blood was drawn from the left cephalic vein to heparinized tubes at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 24, and 48 h. Plasma concentrations were quantified using a validated HPLC method, and the data were analyzed using PKanalix™ software with a non-compartmental approach. Concentrations of imipramine remained quantifiable up to 1.5 hr after administration under both conditions. Desipramine, in both feeding states, was detectable for a short duration, but not quantifiable. No significant differences were observed in the PK parameters of imipramine between the fasting and fed states. The rapid attainment of maximum concentration (C_max) occurred within 0.25 h, indicating a swift absorption rate. Notably, the terminal half-life in dogs was remarkably short at 0.25 h, prompting a re-evaluation of dosing strategies. Considering the recommended therapeutic plasma concentrations in humans, the administered dose might result in effective levels for a brief period of time. Future research should explore intravenous administration, multiple-dose studies, and metabolic investigations to further elucidate imipramine's PK in dogs.

01 Dec 2024·NEUROSCIENCE

The effects of chronic desipramine treatment on neurotrophin-3 in the brain of mice with selective depletion of CREB and CREM in noradrenergic neurons

Article

Author: Rafa-Zabłocka, Katarzyna ; Nalepa, Irena ; Kreiner, Grzegorz

The disturbances in neurotrophic support are thought to be one of the main causes of depression, which depend not only on the neurotrophins themselves but also on the molecules regulating their synthesis and effector functions. One such molecule is cAMP responsive element binding protein (CREB), which role in depression and antidepressant drugs mechanism of action has been extensively studied. However, CREB's effects vary depending on brain structure, necessitating specific transgenic models for studying its function. Moreover, deletion of CREB enhances cAMP response element modulator (CREM) expression, suspected to compensate for CREB in its absence. Previously, mice lacking CREB in noradrenergic neurons and CREM (Creb1^DbhCreCrem-/-) showed to be insensitive to acute desipramine, whereas mice lacking only CREB (Creb1^DbhCre) showed similar effects as wild type animals (w/t). As neurotrophic changes require chronic antidepressant treatment, in current study mice (w/t, Creb1^DbhCre and Creb1^DbhCreCrem-/-; both males and females) were given desipramine for 21 days, to assess the effects of the drug on CREB, neurotrophins and their receptors in the hippocampus and prefrontal cortex. Interestingly, desipramine had no effect on CREB in neither of studied groups. However, both male and female mice lacking CREB and CREM displayed alterations in neurotrophin-3 (NTF3) expression or protein levels, modulated by desipramine. These findings suggest NTF3 is connected with inhibited response to acute and probably chronic desipramine administration in Creb1^DbhCreCrem-/- mice, although in w/t chronic desipramine had no effect on NTF3. Nevertheless, our findings give insight into the role of non-BDNF neurotrophins in the mechanism of antidepressant drugs.

News (Medical) associated with Desipramine Hydrochloride

06 May 2024

·www.biospace.com

Boehringer Ingelheim shares positive results from the first study worldwide in diabetic macular ischemia

Boehringer Ingelheim today presented positive data from the HORNBILL Phase I/IIa study of BI 764524, the first ever study exploring a potential treatment for people living with diabetic macular ischemia (DMI). The study found that BI 764524 was well tolerated following intravitreal administration of single and multiple doses, meeting its primary safety endpoints and showed early signs of potential efficacy.1 DMI is a common, irreversible complication of diabetic retinopathy (DR) that may lead to blindness.12,3,4 It can develop when the light sensitive tissues of the central retina do not receive adequate blood supply over a longer time. There are currently no approved treatments for DMI. The current standard of care for advanced DR includes intravitreal anti-VEGF treatment or invasive laser treatment. However, some patients’ conditions progress despite this treatment.5 BI 764524 uses a novel mode of action by inhibiting the Sema3A pathway to re-vascularize ischemic areas and potentially overcome the limitations of anti-VEGF and laser treatments.1 “The results from the HORNBILL study are really encouraging. They suggest there may be a pathway for earlier intervention that could decrease the risk of, and maybe even prevent, people with diabetic retinopathy from developing irreversible and vision-threatening complications, such as DMI,” said Quan Dong Nguyen, MD, MSc, FARVO, FASRS, Professor of Ophthalmology at the Byers Eye Institute, Professor of Medicine and of Pediatrics at Stanford School of Medicine, and Principal and Coordinating Investigator of the trial. “Retinal non-perfusion is a key driver of vision loss in people living with diabetic retinopathy. However, until the HORNBILL study, retinal non-perfusion has not been explored as a potential treatment target.” “Vision loss associated with retinal conditions such as diabetic retinopathy and DMI has a devastating impact on quality of life. Today’s results are an important step towards achieving our aspiration of developing precision therapies delivering the right treatment for the right patient at the right time to prevent vision loss before irreversible damage occurs,” said Ulrike Graefe-Mody, Ph.D., Head of Retinal Health at Boehringer Ingelheim. “We’re looking forward to start a Phase IIb study to further explore the safety and efficacy of BI 764524.” HORNBILL is one of 23 abstracts being presented at the Association for Research in Vision and Ophthalmology (ARVO) Annual meeting 2024, spanning Boehringer Ingelheim’s retinal health portfolio, including other studies of retinal non-perfusion and diabetic retinopathy, geographic atrophy and neovascular age-related macular degeneration. About the HORNBILL study The HORNBILL study consisted of two parts (single rising dose (SRD), N=12 and multiple dose (MD), N=31) both of which met the primary safety endpoints of number of patients with dose-limiting adverse events (SRD) and treatment-related adverse events(MD).1 The study also met its pre-specified criterion for early efficacy of foveal avascular zone area stabilization versus sham at week 16 (p<0.2).1 This suggests that BI 764524 may positively impact retinal non-perfusion and potentially halt the progression of capillary loss.1 The upcoming CRIMSON trial, a Phase IIb trial, will assess safety and efficacy of BI 764524 in patients with DR further and start recruiting later this year. Notes to Editors: About the trial (NCT04424290) This Phase I/IIa trial assessed the tolerability of BI 764524 in people with diabetic retinopathy (DR) with diabetic macular ischemia (DMI) who have previously been treated with panretinal photocoagulation.1 The trial consisted of a single rising dose (SRD) part followed by a multiple dosing (MD) part, with BI 764524 administered via intravitreal injection.1 Single rising dose part In the non-randomized, open-label, SRD part, 12 patients received intravitreal BI 764524 doses: 0.5 (n=3), 1.0 (n=3), or 2.5 mg (n=6).1 The primary endpoint was the number of patients with dose-limiting events (DLEs); secondary endpoints were the number of patients with drug-related adverse events (AEs) and any ocular AEs.1 Patients in the SRD part had a mean age of 61.8 years.1 No DLEs were reported in the SRD part.1 There were five ocular AEs in four patients in the study eye, none related to the study drug. The highest tested dose (BI 764524 2.5 mg) was considered safe and applied in the MD part.1 Multiple dosing part In the randomized, masked, sham-controlled, MD part, 31 patients received three intravitreal doses of BI 764524 2.5 mg (n=21) or sham injection procedures (n=10) at 4-week intervals (baseline, week 4, and week 8), followed by 14 weeks of follow-up until the end of study at week 22.1 The primary endpoint was the number of patients with drug-related AEs; secondary endpoints included number of patients with ocular AEs, change from baseline in foveal avascular zone (FAZ) area, best corrected visual acuity (BCVA) and central retinal thickness (CRT).1 Patients in the MD part had a mean age of 59.5 years.1 There were seven patients with ocular AEs (study eye; three patients with four AEs for BI 764524, four patients with six AEs for sham), one of which was reported as related to the study drug (vitreous floater).1 In addition, there was one systemic AE (increase deemed related to the study drug by the investigator). There were no cases of intraocular inflammation or occlusive retinal vasculitis.1 At baseline, mean BCVA was 65.2 letters, mean FAZ area was 0.65 mm, and mean CRT was 252 mm.1 The HORNBILL study met its pre-specified criterion for early efficacy of FAZ area stabilization versus sham at week 16 (p<0.2). Over the short trial period, other secondary efficacy endpoints showed no relevant change. About BI 764524 BI 764524 is a humanized monoclonal anti-Sema3A antibody intended to re-vascularize ischemic areas and reduce leakage in the retina, offering the potential to address retinal non-perfusion in retinal diseases. The compound was discovered and developed by Boehringer Ingelheim and is part of its research and development portfolio in retinal conditions. About diabetic retinopathy and diabetic macular ischemia Diabetic retinopathy affects 1 in 3 people with diabetes and is the leading cause of vision loss in adults of working age. It is a growing epidemic that is expected to increase as the incidence of diabetes escalates across the globe. Diabetic macular ischemia (DMI) is a complication of diabetic retinopathy which can lead to slowly progressing, irreversible vision loss. About Boehringer Ingelheim Boehringer Ingelheim is working on breakthrough therapies that transform lives, today and for generations to come. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term, sustainable perspective. More than 53,000 employees serve over 130 markets in the two business units Human Pharma and Animal Health. Learn more at Boehringer Ingelheim’s Intended Audiences Notice This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business. References 1 Nguyen QD, Jhaveri C, Habib MS. Oral presentation at the Association for Research in Vision and Ophthalmology (ARVO) 2024. Abstract number: 959 2 Marques IP, et al. Diabetes 2019;68:648–653 3 Sim DA, et al. Invest Ophthalmol Vis Sci 2013;54:2353–2360 4 Tey KY, et al. Eye Vis (Lond) 2019;6:37 5 Ip MS, et al. Ophthalmology 2014;122:367–374

Clinical ResultPhase 2

22 Nov 2023

·www.prnewswire.com

Novel MRI Reveals Brain Changes in Long-COVID Patients

CHICAGO, Nov. 22, 2023 /PRNewswire/ -- People with long COVID exhibit patterns of changes in the brain that are different from fully recovered COVID-19 patients, according to research being presented next week at the annual meeting of the Radiological Society of North America (RSNA). "To the best of our knowledge, this is the first study comparing patients with long COVID to both a group without history of COVID-19 and a group that went through a COVID-19 infection but is subjectively unimpaired," said one of the study's lead authors, Alexander Rau, M.D., resident in the Departments of Neuroradiology and Diagnostic and Interventional Radiology at University Hospital Freiburg in Freiburg, Germany. After infection with COVID-19, as many as 10-25% of patients may develop a post-COVID condition commonly referred to as "long COVID." People with long COVID may experience a wide variety of symptoms, including difficulty concentrating ("brain fog"), change in sense of smell or taste, fatigue, joint or muscle pain, shortness of breath, digestive symptoms, and more. These symptoms may persist for weeks, months, or—as is only now becoming apparent—years after COVID-19 infection. However, the basis of this condition is poorly understood. Diffusion microstructure imaging (DMI), a novel MRI technique, is a promising approach to fill this gap. DMI looks at the movement of water molecules in tissues. By studying how water molecules move in different directions and at various speeds, DMI can provide detailed information on the microstructure of the brain. It can detect even very small changes in the brain, not detectable with conventional MRI. For this prospective, cross-sectional study, Dr. Rau and colleagues compared MRI brain scans of three groups: 89 patients with long COVID, 38 patients that had contracted COVID-19 but did not report any subjective long-term symptoms, and 46 healthy controls with no history of COVID-19. The researchers first compared the cerebral macrostructure of these three groups to test for atrophy or any other abnormalities. Next, they used DMI to gain a deeper insight into the brain. The three groups were compared to reveal group differences in the brain's microstructure. DMI parameters were read for the gray matter in the brain. Additionally, whole brain analyses were employed to reveal the spatial distribution of alterations and associations with clinical data, including long-COVID symptoms like fatigue, cognitive impairment or impaired sense of smell. The results showed no brain volume loss or any other lesions that might explain the symptoms of long COVID. However, COVID-19 infection induced a specific pattern of microstructural changes in various brain regions, and this pattern differed between those who had long COVID and those who did not. "This study allows for an in vivo insight on the impact of COVID-19 on the brain," Dr. Rau said. "Here, we noted gray matter alterations in both patients with long-COVID and those unimpaired after a COVID-19 infection. Interestingly, we not only noted widespread microstructural alterations in patients with long COVID, but also in those unimpaired after having contracted COVID-19." The findings also revealed a correlation between microstructural changes and symptom-specific brain networks associated with impaired cognition, sense of smell and fatigue. "Expression of post-COVID symptoms was associated with specific affected cerebral networks, suggesting a pathophysiological basis of this syndrome" Dr. Rau said. The researchers hope to reexamine the patients in the future, recording both clinical symptoms and changes to the brain's microstructure. Despite these brain imaging findings, it remains unclear why some people develop long COVID while others do not, although previous studies have identified risk factors including female sex, older age, higher body mass index, smoking, preexisting comorbidities, and previous hospitalization or intensive care unit admission. Co-authors are Jonas A. Hosp, M.D., Nils Schroter, M.D., Marco Reisert, Ph.D., Horst Urbach, M.D., Cornelius Weiller, M.D., and Elias Kellner, Ph.D. Note: Copies of RSNA 2023 news releases and electronic images will be available online at RSNA.org/press23. RSNA is an association of radiologists, radiation oncologists, medical physicists and related scientists promoting excellence in patient care and health care delivery through education, research and technologic innovation. The Society is based in Oak Brook, Illinois. (RSNA.org) Editor's note: The data in these releases may differ from those in the published abstract and those actually presented at the meeting, as researchers continue to update their data right up until the meeting. To ensure you are using the most up-to-date information, please call the RSNA Newsroom at 1-312-791-6610. For patient-friendly information on brain MRI, visit RadiologyInfo.org. SOURCE Radiological Society of North America (RSNA)

Clinical Result

04 Apr 2023

·www.sciencedaily.com

DMI allows magnon-magnon coupling in hybrid perovskites

An international group of researchers has created a mixed magnon state in an organic hybrid perovskite material by utilizing the Dzyaloshinskii--Moriya-Interaction (DMI). The resulting material has potential for processing and storing quantum computing information. An international group of researchers has created a mixed magnon state in an organic hybrid perovskite material by utilizing the Dzyaloshinskii-Moriya-Interaction (DMI). The resulting material has potential for processing and storing quantum computing information. The work also expands the number of potential materials that can be used to create hybrid magnonic systems. In magnetic materials, quasi-particles called magnons direct the electron spin within the material. There are two types of magnons -- optical and acoustic -- which refer to the direction of their spin. "Both optical and acoustic magnons propagate spin waves in antiferromagnets," says Dali Sun, associate professor of physics and member of the Organic and Carbon Electronics Lab (ORaCEL) at North Carolina State University. "But in order to use spin waves to process quantum information, you need a mixed spin wave state." "Normally two magnon modes cannot generate a mixed spin state due to their different symmetries," Sun says. "But by harnessing the DMI we discovered a hybrid perovskite with a mixed magnon state." Sun is also a corresponding author of the research. The researchers accomplished this by adding an organic cation to the material, which created a particular interaction called the DMI. In short, the DMI breaks the symmetry of the material, allowing the spins to mix. The team utilized a copper based magnetic hybrid organic-inorganic perovskite, which has a unique octahedral structure. These octahedrons can tilt and deform in different ways. Adding an organic cation to the material breaks the symmetry, creating angles within the material that allow the different magnon modes to couple and the spins to mix. "Beyond the quantum implications, this is the first time we've observed broken symmetry in a hybrid organic-inorganic perovskite," says Andrew Comstock, NC State graduate research assistant and first author of the research. "We found that the DMI allows magnon coupling in copper-based hybrid perovskite materials with the correct symmetry requirements," Comstock says. "Adding different cations creates different effects. This work really opens up ways to create magnon coupling from a lot of different materials -- and studying the dynamic effects of this material can teach us new physics as well." The work appears in Nature Communications and was primarily supported by the U.S. Department of Energy's Center for Hybrid Organic Inorganic Semiconductors for Energy (CHOISE). Chung-Tao Chou of the Massachusetts Institute of Technology is co-first author of the work. Luqiao Liu of MIT, and Matthew Beard and Haipeng Lu of the National Renewable Energy Laboratory are co-corresponding authors of the research.

100 Deals associated with Desipramine Hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D00812	Desipramine Hydrochloride	N06AA01	DB01151

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Depressive Disorder	US	Validus Pharmaceuticals LLC	20 Nov 1964

Clinical Result

Indication

Phase

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01899326 (CTgov)	Not Applicable	Refractory Multiple Myeloma	10	Laboratory Biomarker Analysis+Filgrastim+Desipramine Hydrochloride	sxnvlzkoxz(rwcgzhvhgq) = rpkrzhbhvp axdtttutlo (iqbzldbaxh, snznubbqux - qxloevlcym) View more	-	28 Mar 2023
ISTH2021	Not Applicable	-	-	Desipramine	banptrvmva(dudrrjqpwt) = bnvpofqvzt vlzlsonlwm (pcuygdflrh )	-	17 Jul 2021
ISTH2021	Not Applicable	-	-	PRP pre-incubated with 10μM desipramine	banptrvmva(dudrrjqpwt) = jehzbqludt vlzlsonlwm (pcuygdflrh )	-	17 Jul 2021
NCT03726996 (CTgov)	Phase 4	Neuroaxonal Dystrophies	4	Desipramine	hcektgloww(gykombxfus) = fcemfgmuqa vwrhabzfsk (njtnnpzlmf, bacaipxtql - bwvsujfynt) View more	-	14 Oct 2020
NCT01411085 (RADIAUS, CTgov)	Phase 2	Alcoholism \| Schizophrenia	12	Risperidone+Desipramine	ljbqehvjgb(qflfbwfseb) = pktvxcwcvl pdqdlnihfr (ccsmdbgakg, covulbgiws - ncklnshpbm) View more	-	23 Mar 2018
NCT00338962 (CTgov)	Phase 3	Alcoholism \| Depressive Disorder \| Stress Disorders, Post-Traumatic	88	paroxetine+Naltrexone (Paroxetine and Naltrexone)	ujyzpizbbr(glxlxjprxc) = qmkdgegsvd jxcepyqtqz (tjoxsohcsb, amzurydpdt - mkkysvhhun) View more	-	05 Feb 2016
NCT00338962 (CTgov)	Phase 3		88	Placebo+paroxetine (Paroxetine and Placebo)	ujyzpizbbr(glxlxjprxc) = ldqydlzwya jxcepyqtqz (tjoxsohcsb, hkzcwuomkl - ktgtksibcs) View more	-	05 Feb 2016
NCT00166114 (CTgov)	Phase 4	Depressive Disorder, Major	40	Escitalopram (Escitalopram)	eayyyoegtz(chlswyqths) = dwbfjxmpya gwewrkxjih (nyzsewbnuf, moskkopsje - ajvxpycdqw) View more	-	23 Jul 2015
NCT00166114 (CTgov)	Phase 4	Depressive Disorder, Major	40	Desipramine (Desipramine)	eayyyoegtz(chlswyqths) = ikbuvjcdpu gwewrkxjih (nyzsewbnuf, eahbcxsspe - seltldaqig) View more	-	23 Jul 2015

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