Uremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces.
Uremic toxins such as dihydroxyphenylalanine are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (A7868). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (A7869).
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌物分类
对人类无致癌性（未列入国际癌症研究机构IARC清单）。
No indication of carcinogenicity to humans (not listed by IARC).
来源:Toxin and Toxin Target Database (T3DB)
毒理性
健康影响
长期暴露于尿毒症毒素可能会导致多种疾病，包括肾脏损伤、慢性肾病和心血管疾病。
Chronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease.
◉ Summary of Use during Lactation:Limited data indicate that levodopa is poorly excreted into breastmilk and that the sustained-release product may result in a smaller amount of drug transferred to the breastfed infant than with the immediate-release product. Several studies indicate that levodopa can decrease serum prolactin during lactation. The prolactin level in a mother with established lactation may not affect her ability to breastfeed. The effect of long-term use of levodopa on breastfeeding has not been adequately evaluated, although some mothers were able to successfully breastfeed her infant without apparent harm while using relatively low doses of levodopa and carbidopa for Parkinson's disease.
◉ Effects in Breastfed Infants:One mother with Parkinson's disease took sustained-release levodopa 200 mg and carbidopa 50 mg 4 times daily. She successfully breastfed her infant whose development was normal at 2 years of age.
A 37-year-old Israeli woman with Parkinson's disease became pregnant while taking a continuous infusion of levodopa 20 mg/mL and carbidopa 5 mg/mL gel. She breastfed her infant for 3 months while receiving the drug, although the extent of breastfeeding and the dosage of the gel is not clear from the paper. At 10 months of age, the infant's psychomotor development was deemed to be normal.
◉ Effects on Lactation and Breastmilk:Levodopa decreases serum prolactin in normal women and those with hyperprolactinemia and can suppress inappropriate lactation in galactorrhea, although not consistently. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.
One mother with Parkinson's disease took sustained-release levodopa 200 mg and carbidopa 50 mg 4 times daily. She successfully breastfed her infant.
On postpartum day 3, 5 women were given a single oral dose of 500 mg of levodopa or bromocriptine 5 mg followed by a single oral dose of metoclopramide 10 mg 3 hours later. Bromocriptine suppressed basal serum prolactin to a greater extent than levodopa. Over the next 3 hours, serum prolactin increased after metoclopramide in the patients who received levodopa, but not in those who received bromocriptine.
Six women who were 2 to 4 days postpartum, but were not nursing, were given 500 mg of levodopa orally on one day and 100 mg of levodopa plus 35 mg of carbidopa orally on the next day. Both regimens suppressed basal serum prolactin levels. However, levodopa alone caused an 78% decrease in prolactin while the lower dose combination produced only a 51% decrease. The maximal effect occurred about 2 hours after the dose with both regimens.
Seven women in the first week postpartum who were breastfeeding about 7 times daily were given levodopa 500 mg orally and their serum prolactin responses was studied. The following day, they started carbidopa 50 mg orally every 6 hours for 2 days. On the third day, they received a single dose of carbidopa 50 mg plus levodopa 125 mg orally. Decreases in basal serum prolactin occurred by 30 minutes after the levodopa and after 45 minutes with the combination. Decreases were maximum at 120 minutes after the dose and were 62% with levodopa alone and 48% with the combination, although the difference between the 2 regimens was not statistically significant.
A 37-year-old Israeli woman with Parkinson's disease became pregnant while taking a continuous infusion of levodopa 20 mg/mL and carbidopa 5 mg/mL gel. She breastfed her infant for 3 months while receiving the drug, although the extent of breastfeeding and the dosage of the gel is not clear from the paper.
[EN] A CONJUGATE OF A CYTOTOXIC AGENT TO A CELL BINDING MOLECULE WITH BRANCHED LINKERS<br/>[FR] CONJUGUÉ D'UN AGENT CYTOTOXIQUE À UNE MOLÉCULE DE LIAISON CELLULAIRE AVEC DES LIEURS RAMIFIÉS
申请人：HANGZHOU DAC BIOTECH CO LTD
公开号：WO2020257998A1
公开（公告）日：2020-12-30
Provided is a conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.
[EN] CROSS-LINKED PYRROLOBENZODIAZEPINE DIMER (PBD) DERIVATIVE AND ITS CONJUGATES<br/>[FR] DÉRIVÉ DE DIMÈRE DE PYRROLOBENZODIAZÉPINE RÉTICULÉ (PBD) ET SES CONJUGUÉS
申请人：HANGZHOU DAC BIOTECH CO LTD
公开号：WO2020006722A1
公开（公告）日：2020-01-09
A novel cross-linked cytotoxic agents, pyrrolobenzo-diazepine dimer (PBD) derivatives, and their conjugates to a cell-binding molecule, a method for preparation of the conjugates and the therapeutic use of the conjugates.
Imaging compounds, methods of making imaging compounds, methods of imaging, therapeutic compounds, methods of making therapeutic compounds, and methods of therapy
申请人：Chen Xiaoyuan
公开号：US20080267882A1
公开（公告）日：2008-10-30
Embodiments of the present disclosure provide for RGD compounds that include a multimeric RGD (arginine-glycine-aspartic acid (Arg-Gly-Asp)) peptide, methods of making the RGD compound, pharmaceutical compositions including RGD compound, methods of using the RGD compositions or the pharmaceutical compositions including RGD compositions, methods of diagnosing and/or targeting angiogenesis related disease and related biological events, kits for diagnosing and/or targeting angiogenesis related disease and related biological events, and the like. In addition, the present disclosure includes compositions used in and methods relating to non-invasive imaging (e.g., positron emission tomography (PET) imaging) of the RGD compounds in vivo.
[EN] 3-(6-ALKOXY-5-CHLOROBENZO[D]ISOXAZOL-3-YL)PROPANOIC ACID USEFUL AS KYNURENINE MONOOXYGENASE INHIBITORS<br/>[FR] ACIDE 3-(6-ALKOXY-5-CHLOROBENZO[D]ISOXAZOL-3-YL)PROPANOÏQUE UTILE EN TANT QU'INHIBITEUR DE LA KYNURÉNINE MONOOXYGÉNASE
申请人：GLAXOSMITHKLINE IP DEV LTD
公开号：WO2016097144A1
公开（公告）日：2016-06-23
Compound of formula (I) wherein R1 is heteroaryl either unsubstituted or substituted by methyl, ethyl, halo or =O; and R2 is H, methyl or ethyl; and salts thereof are KMO inhibitors and may be useful in the treatment of various disorders, for example acute pancreatitis, chronic kidney disease, acute kidney disewase, acute kidney injury, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, HIV infection, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure.
[EN] AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS<br/>[FR] DÉRIVÉS AMINOPYRIMIDINIQUES UTILISÉS COMME MODULATEURS DE LRRK2
申请人：HOFFMANN LA ROCHE
公开号：WO2013079505A1
公开（公告）日：2013-06-06
Compounds of the formula (I): or pharmaceutically acceptable salts thereof, wherein A, X, R1, R2, R3 and R4 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.
