Urea cycle disorders (UCD) are rare diseases in China, would lead to high mortality and disability, which require long-term management due to the recurrent symptoms. This multi-center, prospective, single-arm study was designed to assess the efficacy and safety of Glycerol Phenylbutyrate for Chinese pediatric patients with UCD, to provide the additional references and treatment options for Chinese UCD patients, and enhance the clinical management of UCD in China. This study primarily observes patients with UCD who are on long-term treatment with glyceryl phenylbutyrate, the total planned observation period is 5 years.

开始日期2025-07-01

申办/合作机构-

NCT06953505

/ Not yet recruitingN/A

Pilot Study of At Home Ammonia Monitoring in Patients With an Inborn Error of Ammonia Metabolism

The goal of this observational study is to learn if people with certain ammonia metabolism disorders will measure their ammonia levels at home.
The main question it aims to answer is:
• Will participants measure their ammonia every day?
Participants will be asked to:
* Attend three in-person study visits at the clinic.
* Measure temperature, heart rate, and blood oxygen every day.
* Complete a short survey every day.
* Measure ammonia every day.

开始日期2025-06-01

申办/合作机构

Sequitur Health Corp.

[+1]

NCT06920238

/ Recruiting临床1期IIT

A Phase I Single-Arm Trial to Test the Use of a Generative AI (Gen-AI) Chatbot for Anxiety and Depression Among Persons With Cannabis Use Disorder (CUD)

The goal of this clinical trial is to learn if Therabot-CALM (Cannabis, Anxiety, Low Mood) has acceptability among users and could work to improve the symptoms of persons with cannabis use disorder and anxiety and/or depression. The main question it aims to answer is:
What is the usability, feasibility, and acceptability of Therabot-CALM in persons with Cannabis Use Disorder and Anxiety and/or Depression?
Participants will
* Take a screening questionnaire
* Participate in two virtual 1-hour interviews to provide feedback on app design and suggest features.
* Engage with Therabot-CALM in a 4-week clinical trial and provide feedback on their app experience in a third virtual interview

开始日期2025-04-01

申办/合作机构

Trustees of Dartmouth College

[+1]

100 项与高氨血症相关的临床结果

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100 项与高氨血症相关的转化医学

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0 项与高氨血症相关的专利（医药）

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7,588

项与高氨血症相关的文献（医药）

2025-12-01·Current Neurology and Neuroscience Reports

Hepatic Encephalopathy: Current Thoughts on Pathophysiology and Management

Review

作者: Pan, Kausik ; Chakravarty, Ambar ; Sen, Barun Kumar

PURPOSE OF REVIEWThis review highlights the causes, types and clinical staging of hepatic encephalopathy (HE). Current concepts on the probable pathogenetic mechanisms and currently practiced therapeutic options are discussed.RECENT FINDINGSHE may be covert and overt. Also known as minimal HE. Covert HE, where there are behavioral abnormalities and impairment in activities of daily living with intact sensorium. The pathophysiology of HE remains poorly understood. There is disturbance of the urea cycle due to liver disease leading to increased production of ammonia. The ammonium ion enters the astrocytes along with glutamate (converted to glutamine by ammonia) and myo-inositol, thereby increasing the osmolality of the astrocytic cytoplasm. This osmotic gradient results in accumulation of water inside the astrocytes resulting in cerebral edema and increase in brain volume. Additionally, current research has noted the role of cerebral oxidative/nitrosative stress and the synergistic effects of increased cerebral ammonia and alteration in neurotransmitters, neurometabolites, and cortical excitability due to systemic inflammation. In advanced liver disease with systemic infection or inflammation, neuroinflammatory processes play significant role in the development of HE. Inflammatory cytokines like TNF-α, IL-6, IL-17 in presence of hyperammonemia have been found to induce neurotoxicity of ammonia by passing through the blood brain barrier and causing enlarged/swollen pale astrocytes, resulting in HE. Disrupted enterohepatic circulation in end stage liver disease also causes elevation of bile acids which induces neuroinflammation. Manganese and zinc play as co-factors of enzymatic reaction. These metal deposition causes multiple psychomotor symptoms observed in HE. The gut environment has a major impact on brain function in patients with HE. Toxins such as ammonia and inflammatory cytokines produced by this impaired intestinal flora access the circulation through porto-systemic anastomoses and exacerbate or precipitate HE. Finally, as a result of recurrent cerebral edema from astrocytic dysfunction and neuroinflammation, permanent neurodegeneration occurs with cognitive decline and motor disturbances, especially parkinsonian features and gait disturbances. This is the stage of chronic hepatic encephalopathy. Currently L-ornithine L-aspartate (LOLA) is being used to lower the ammonia level by stimulating the urea cycle. HE comprises a broad spectrum of neurological and/or psychiatric abnormalities caused by hepatic insufficiency and/or portal-systemic shunting in the absence of any other causes of brain dysfunction. HE may be caused or precipitated by several factors like infections, intoxications and drugs. The encephalopathic features may be covert or overt. The pathogenetic mechanisms for HE may be different. In the presence of liver disease, HE primarily results from disturbed urea cycle with hyperammonemia causing astrocytic swelling and cerebral edema. Porto-systemic anastomoses with intact liver function can cause HE by allowing ammonia and other toxins produced by the gut microbial flora and allowing these to bypass detoxification by the liver and exposing the brain to their harmful effects. Principles of therapy are twofold. First protecting the liver and the brain from gut generated ammonia and other toxins by ensuring smooth bowel function and avoiding stagnation with the use of osmotic laxatives like lactulose or lactitol and also reducing the gut microbial load with use of anti-bacterials/bacteriophages like neomycin and rifaximin along with metronidazole. Second, reducing the already generated cerebral edema by use of mannitol and appropriate ventilatory support. Currently L-ornithine L-aspartate (LOLA) is being used to reduce the ammonia load to the liver. LOLA is a stable compound formed from two amino acids. L-ornithine plays a crucial role in stimulating the urea cycle, leading to a reduction in ammonia levels. Both L-ornithine and L-aspartate serve as substrates for the enzyme glutamate transaminase, and their administration results in elevated glutamate concentrations. Ammonia is subsequently utilized in the conversion of glutamate to glutamine through the action of glutamine synthetase. Finally in resistant cases the use of liver transplant needs to be considered. Alternatively extracorporeal liver assist devices may be used like Molecular Adsorbent Recirculating System (MARS) or Single-Pass Albumin Dialysis (SPAD).

2025-08-01·Addictive Behaviors

Relations between adverse childhood experiences, racial and ethnic Identity, and cannabis use outcomes

Article

作者: Espinosa, Adriana ; Gette, Jordan A

Adverse childhood experiences (ACEs) and age of cannabis use onset are associated with cannabis use disorder (CUD), but their differential effect across race and ethnicity is unknown. Using NESARC-III, we examined ACEs, age of onset, and their interaction on lifetime cannabis use and CUD across racial and ethnic groups (Non-Hispanic White, Hispanic, Black/African American, Asian, American Indian/Alaska Native). ANOVAs found that American Indian/Alaska Native individuals reported the greatest prevalence of lifetime cannabis use and CUD, the greatest mean number of ACEs, and the earliest age of cannabis onset. Using logistic regressions, stratified by race and ethnic groups and adjusted for sociodemographic characteristics, we found that as ACEs increased, the odds of lifetime use (aORs 1.48-2.48), lifetime CUD (aORs 1.45-3.03), and past-year CUD (aORs 1.46-2.28) increased for all groups. The relations between ACEs and CUD were strongest among Asian/Pacific Islander respondents. Among respondents with lifetime use, increased age of onset was associated with lower lifetime CUD (aORs 0.85-0.94) and past-year CUD (aORs 0.88-0.97) for most groups. Three significant interactions between ACEs and age of onset predicting CUD emerged. Among Black and American Indian/Alaska Native individuals with an early age of cannabis initiation, ACEs exhibited a weaker relation with CUD. For White respondents, as number of ACEs increased, the impact of age of onset on CUD development diminished. Our findings highlight ACEs and age of onset as implicated in the progression from cannabis use to CUD and the importance of considering these factors in relation to racial and ethnic identity.

2025-06-01·Talanta

Distance-based quantitation of urinary ammonia using a low-cost cellulose-based thread sensor impregnated with curcumin

Article

作者: Dos Santos, Danilo Martins ; Khachornsakkul, Kawin ; Sonkusale, Sameer ; Rybicki Iv, Frank John

Effective point-of-care (POC) methods for detecting metabolic disorders, such as hyperammonemia, are crucial. Urinary ammonia is an underexplored but physiologically relevant biomarker for such conditions and can be conveniently monitored noninvasively. Conventional detection methods, while reliable, are time-consuming and costly. We propose a green, low-cost microfluidic distance-based thread analytical device (dTAD) that incorporates curcumin for urinary ammonia quantification. Through a simple immersion technique, curcumin was deposited on the surface of cellulose-based threads, resulting in a user-friendly device that correlates ammonia titers to a naked-eye colorimetric distance-based measurement. Curcumin undergoes a color change from yellow to red in the presence of ammonia and demonstrates strong selectivity with major interferants in urine. Moreover, this sensor exhibits a linear range of 20.0-80.0 mmol L^-1 (R² = 0.994) with a limit of detection (LOD) of 5.0 mmol L^-1. The LOD was theoretically predicted using the mass balance volatilization of ammonia along the thread channel in conjunction with Darcy's law. The thread-based device offers significant advantages in terms of simplicity, affordability, versatility, and future scalability. With a total analysis time of 3.0 min, a cost of less than $0.20 per sensor, and a recovery range of 91%-102% in human control urine samples, the device meets the demands of REASSURED (Real-time connectivity, Ease of specimen collection, Affordable, Sensitive, Specific, User-friendly, Rapid and Robust, Equipment-free, and Deliverable) POC diagnostics for the developing world. To the best of our knowledge, this is the first application of a distance-based thread device that quantifies ammonia in biofluid samples.

170

项与高氨血症相关的新闻（医药）

2025-04-23

·梅斯医学

27岁小伙一运动就“虚脱”，竟不是体力差，而是患上了这种罕见代谢病！

27岁的小李（化名）身材清瘦、性格开朗，但过去四年，他反复出现“奇怪”的发作：剧烈运动后就会呕吐、腹泻，甚至昏迷不醒。第一次是在一次登山后，随之而来的还有高氨血症、代谢性酸中毒和心衰……经过抢救才转危为安。此后，小李的生活彻底变了。只要稍微一动多了，就可能出现恶心、无力、呕吐，甚至胸闷气短。多次就诊后，只能以“周围神经病”“高氨血症”来暂时解释症状，但病情始终反复。直到最近一次发作——轻微活动后突发胸闷、气短、心电图异常，心肌酶升高，再次住院。医生在进一步回顾病史、评估症状、并结合氨升高、神经病变、心肌损伤等表现后，终于高度怀疑并进行遗传代谢病相关检测，最终确诊为：迟发型丙酸血症。常染色体隐性遗传病丙酸血症(propionic acidemia，PA)是支链氨基酸和偶数链脂肪酸代谢异常的一种较常见的有机酸血症，为常染色体隐性遗传病，是由于丙酰CoA酶羧化酶活性缺乏，导致体内丙酸及其代谢产物前体异常蓄积，而出现一系列生化异常、神经系统和其他脏器损害症状。不同地区有较大差异，为1/280 000～1/90 000，中国约为1/200 000。丙酸血症虽属于罕见病，但是有机酸血症中常见疾病，患者临床表现缺乏特异性，个体差异较大，可自新生儿到成年发病。临床表现丙酸血症可发生于新生儿至成年，分为早发型（≤3个月）和晚发型（>3个月），以早发型最常见。早发型多在出生后数天内出现代谢失代偿，表现为喂养困难、呕吐、嗜睡、低肌张力等，易误诊为围生期脑损伤等。若不及时治疗，易发展为昏迷甚至死亡，并遗留神经及多器官损害。晚发型常因感染、饥饿、手术等应激诱发，表现为代谢危象及认知障碍。部分患者起病隐匿，出现进食困难、智力运动发育迟缓、癫痫等症状。常见并发症包括脑基底核损伤、心肌病、血细胞减少、肝胰损害、视听障碍及骨质疏松。个别病例表现为肾损伤或孤立性心肌病，提示该病临床谱仍在扩展。诊断对于有脑发育异常、发育迟缓、癫痫、脑瘫、不明原因呕吐、昏迷、酸中毒、心肌病或有相关家族史的高危患儿，应警惕丙酸血症等代谢病，尽早进行血氨、血气、血糖、肝肾功能、心肌酶谱等基础检查，并结合特殊生化分析明确诊断。1. 新生儿筛查与生化分析：通过液相色谱-串联质谱（LC-MS/MS）检测血酯酰肉碱谱，典型患者表现为C3、C3/Co、C3/C2升高，游离肉碱（Co）和甘氨酸水平异常。由于可能存在假阳性或假阴性，应结合尿液有机酸谱（GC-MS）检查，若3-羟基丙酸、甲基枸橼酸、丙酰甘氨酸升高，且甲基丙二酸正常，可提示丙酸血症。2. 酶活性检测：可通过特定方法测定皮肤成纤维细胞或外周血淋巴细胞中的丙酰辅酶A羧化酶活性，辅助诊断。但因检测条件复杂，不适用于常规筛查。3. 基因分析：通过Sanger测序、靶向或全外显子测序检测PCCA或PCCB基因的致病突变可确诊。PCCA突变多为点突变（约80%），PCCB点突变比例更高（约97%）。若未发现双等位基因突变，需进一步做拷贝数变异分析（如qPCR、MLPA、array-CGH）以排除大段缺失或重复。治疗急性期治疗：丙酸血症急性期治疗应以生命支持为核心，纠正酸中毒、电解质紊乱，限制蛋白摄入，积极补充热量（1.5倍基础需求），抑制分解代谢。使用左卡尼汀促进毒物排出，重度高氨血症时可用精氨酸类药物，必要时行透析。特殊配方奶粉应在短期内替代天然蛋白，但应在48小时内恢复部分天然蛋白摄入。稳定期治疗与管理：饮食管理：高热量、低蛋白饮食，补充特殊配方奶粉，天然蛋白摄入量随年龄调整。鼓励母乳喂养，避免饥饿，确保微量营养素摄入。药物治疗：持续口服左卡尼汀维持正常水平；短期使用甲硝唑减少肠道丙酸产生；苯甲酸钠类药物降血氨；必要时使用生长激素。应密切监测代谢指标和生长发育情况，个体化管理。肝移植与新治疗探索：对于反复发作、治疗效果差的患儿，肝移植可显著改善代谢控制和生活质量，提升蛋白耐受力。新兴疗法如酶替代、基因治疗、抗氧化剂及回补疗法仍在研究中，未来或为治疗提供更多选择。参考资料：1.单纯型甲基丙二酸尿症饮食治疗与营养管理专家共识 . 中国实用儿科杂志，2018，33(7)：481-486.2. 高明，张强强，王欣阳,等. 成人迟发型丙酸血症合并心肌病1例. 中国临床案例成果数据库，2024，06(01):E2452-E2452.3.刘怡，杨艳玲. 丙酸血症的筛查、诊断与治疗. 中华实用儿科临床杂志，2019，34(20):1531-1534. DOI:10.3760/cma.j.issn.2095-428X.2019.20.003来源 | 梅斯医学编辑 | wanny神经系统罕见病交流群↓点击下方“阅读原文”，下载梅斯医学APP吧！

2025-04-16

·PRNewswire

PLEOPHARMA, INC. Reports New Patent Issuance

New Patent Issued on April 8, 2025 Patent Protection to March 2041 PHOENIXVILLE, Pa., April 16, 2025 /PRNewswire/ -- PleoPharma, Inc. ("PleoPharma" or the "Company"), a privately held company focused on Cannabis-related health issues, announced today that the U.S. Patent Office has issued a new patent focusing on the treatment of sleep disturbances, including sleep quality and duration, associated with cannabis withdrawal syndrome ("CWS") in patients with cannabis use disorder ("CUD"). "We are pleased to have received our third issued patent. Improving sleep quality, depth and duration for patients suffering from CWS is an important aspect of PP-01 and a tremendous benefit in quality of life, especially for CUD patients who are suffering from CWS," said PleoPharma's CEO, Ginger Constantine, MD. Recently issued U.S. Patent No. 12,268,659, entitled "Methods and Compositions for Treating Cannabis Use Disorder and Mitigating Cannabinoid Withdrawal," contains method of use claims for mitigating CWS, and in particular improving sleep quality, depth and duration, and further claiming specific dose ranges and detailed dosing schedules corresponding to what the Company believes will be the dosing for PP-01. The Company notes that additional patent applications are pending in the US and globally in which it is pursuing further IP development. About cannabis withdrawal/cannabis use disorder The US Government reported that in 2023 (samhsa.gov), ~19.2 million Americans had Cannabis Use Disorder with ~ 1.64 million people receiving treatment (~500k inpatient, ~1.1 million outpatient). The number of individuals who received treatment for cannabis related health problems has grown by an average of 28% annually from 2018 to 2023. People with Cannabis Use Disorder commonly experience significant withdrawal symptoms, known as Cannabis Withdrawal Syndrome, that can make it extremely difficult to reduce or discontinue cannabis. There are currently no FDA approved medications for the treatment of cannabis withdrawal syndrome or cannabis use disorder. PleoPharma recognizes that many people do use cannabis responsibly, but as with alcohol, some may develop a dependence. Our mission is to provide a treatment option for those who want help reducing or discontinuing cannabis. About PleoPharma, Inc. PleoPharma, Inc. is a clinical stage development company in the neuropsych and addiction space with a lead asset, PP-01, that is being developed as the first FDA approved treatment of Cannabis Withdrawal Syndrome in people with Cannabis Use Disorder. The PleoPharma team includes a world class management team and board of directors who have produced multiple high value exits, >50 worldwide product approvals, and 100+ INDs. For more information on PleoPharma, please visit or email Dawn Halkuff, head of Investor Relations at [email protected]. This release includes 'forward-looking statements' regarding the operations of PleoPharma, Inc., actual results may differ from its expectations, estimates, and projections and, consequently, you should not rely on these forward-looking statements as predictions of future events. All statements other than statements of historical facts contained herein are forward-looking statements that reflect the current beliefs and expectations of management of PleoPharma. These forward-looking statements involve significant risks and uncertainties that could cause the actual results to differ materially from those discussed in the forward-looking statements. PleoPharma does not undertake or accept any obligation or undertaking to release any updates or revisions to any forward-looking statements to reflect any change in its expectations or any change in events, conditions or circumstances on which any such statement is based. SOURCE PleoPharma, Inc WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

上市批准

2025-04-10

·药筛

这个品种有参比、有原料、有指南、有市场，就是没有一致性评价申报？

今天，我注意到一个产品，有原研进口，有参比制剂登记信息，有原料药，有临床指南推荐，也有不小的市场规模，专利已经过期，但至今没有企业做一致性评价。这个品种就是利福昔明片。利福昔明片由意大利Alfa Wassermann研发，其活性成分为利福昔明α晶型，该晶型在胃肠道中几乎不被吸收（吸收率＜1%），主要发挥局部抗菌作用，适用于肠道感染、肝性脑病等。产品1988年就在意大利上市，原研2002年就已获批进口。国内也有多个仿制药批文。属于医保乙类。利福昔明片的适应症包括肠道感染、预防胃肠手术前后的感染，还可以治疗肝性脑病。这个适应症，患者还是很多的。说明书适应症：对利福昔明敏感的病原菌引起的肠道感染（包括急性和慢性肠道感染、腹泻综合征、夏季腹泻、旅行者腹泻和小肠结肠炎等）；预防胃肠道手术期时术前术后的感染性并发症；用于高氨血症（肝性脑病）的辅助治疗。产品也被多个临床指南推荐。是肝性脑病的一线推荐用药，还被推荐用于肠易激综合症等。国内医院市场销售额每年都在增长，2023年超过了6000万元，销售额几乎全部来自原研，国产只有四川百利有一点点的销售数据。2021年时，国内就已有参比制剂登记。也有多个原料药登记信息。但是，到目前，还没有提交一致性评价补充申请，也没有提交新仿制上市申请。在仿制药卷上天，立项困难的时候，咋就没企业考虑这个品种呢？仅仅是因为这个产品肠道不吸收，无法做BE，有可能需要做验证性临床的原因吗？请教懂行的朋友，帮忙指点下，到底什么原因？用摩熵药筛小程序，快速查询产品申报进展！

一致性评价