STUDIES WITH STREPTOZOTOCIN LABELLED WITH (14)C IN DIFFERENT POSITIONS INDICATE THAT ITS RAPID METABOLISM IN RAT ... RESULTS IN METABOLITE DERIVED FROM METHYL BEARING NITROSOUREIDO SIDECHAIN. /SRP: DIAZOMETHANE/
来源:Hazardous Substances Data Bank (HSDB)
代谢
在老鼠尿液中检测到五种尿液代谢物；其中两种是抗生素的α和β-异构体。
/IN MICE URINE/ FIVE URINARY METABOLITES WERE DETECTED; 2 OF THEM WERE THE ALPHA AND BETA-ANOMERS OF THE ANTIBIOTIC.
Streptozocin and metabolites have a short distribution phase (t1/2 6 min) followed by possibly two elimination phases representing active metabolites (t1/2 beta 3.5 hr, t1/2 gamma 40 hr).
Streptozocin is not orally active. After intravenous administration, it is rapidly cleared from plasma and is undetectable after three hours. Metabolites are detected in plasma for up to 24 hours. The drug concentrates in certain tissues; the liver and kidneys contain the highest levels, and pancreas also concentrates streptozocin. Parent drug and metabolites are eliminated rapidly by the kidney; 60% to 70% of a dose is recovered in urine within four hours. Only 10% to 20% of an excreted dose is parent drug.
Serum aminotransferase elevations occur in up to two-thirds of patients treated with streptozocin, but the abnormalities are generally mild, transient and not associated with symptoms or jaundice. Hepatotoxicity is more common with daily dosing and high doses of streptozocin, but with higher doses renal and hematologic toxicities usually overshadow hepatic injury. There have been two reports of rapidly progressive and fatal acute liver failure in patients treated with streptozocin. In one instance, no other chemotherapy was given, in another fluorouracil was coadministered and the patient presented with fever, anuria, acute hepatitis [ALT 1280, bilirubin 11.9, prothrombin index 10%, eosinophils 2600/ µL] at the end of a 5 day course of treatment. In contrast, there have been no individual published case reports of self-limited clinically apparent liver injury attributed to streptozocin, but it has had limited use, as pancreatic islet cell carcinoma and neuroendocrine tumors are rare.
The Human Health Assessment Group in EPA's Office of Health and Environmental Assessment has evaluated streptozotocin for carcinogenicity. According to their analysis, the weight-of-evidence for streptozotocin is group B2, which is based on sufficient evidence in animals. No data are available in humans. As a group B2 chemical, streptozotocin is considered probably carcinogenic to humans.
No data are available in humans. Sufficient evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 2B: The agent is possibly carcinogenic to humans.
IN ALL THESE SPECIES /MICE, RATS, CATS, MONKEYS & DOGS/ STR /STREPTOZOTOCIN/ GIVEN PARENTERALLY ... MARKEDLY CONCENTRATED IN LIVER & KIDNEY; FOR EXAMPLE, IN DOGS ... RETAINED IN LIVER FOR MANY HR AFTER ... NO LONGER ... DETECTED IN BLOOD .
STREPTOZOTOCIN (NSC-85998) WAS RAPIDLY EXCRETED IN URINE OF TREATED MICE; 72% OF AN INJECTED DOSE IN THE 4-HR URINE. FIVE URINARY METABOLITES WERE DETECTED ... .
Following intraperitoneal or IV administration of streptozocin in animals, the drug and its metabolites are rapidly distributed mainly into the liver, kidneys, intestine, and pancreas, with lower concentrations being distributed into skeletal muscle, spleen, lungs, heart, and thymus. Concentrations of the drug or its metabolites in the liver, kidneys, intestine, and pancreas are consistently higher than those in plasma. Streptozocin does not appear to cross the blood-brain barrier in animals or humans; however, in humans, metabolites of streptozocin readily distribute into CSF. ... The drug readily crosses the placenta in monkeys.
来源:Hazardous Substances Data Bank (HSDB)
文献信息
Materials and methods for suppressing and/or treating bacterial infections and related symptoms
申请人：Indiana University Research and Technology Corporation
公开号：US10933075B2
公开（公告）日：2021-03-02
Various aspects and embodiments disclosed herein relate generally to the modelling, treatment, reducing resistence to the treatment, prevention, and diagnosis of diseases/symptoms induced by infectious bacteria. Embodiments include methods of treating a bacterial infection, comprising the steps of: providing to a patient diagnosed with staphylococcal infection at least one therapeutically effective dose of a compound having an anti-virulence effect.
Three-dimensional vascular network assembly from induced pluripotent stem cells
申请人：THE JOHNS HOPKINS UNIVERSITY
公开号：US11332717B2
公开（公告）日：2022-05-17
Early vascular cells (EVCs), including endothelial cells and pericytes, are generated from hiPSCs. Unlike the isolated endothelial progenitor cells, the differentiated ECs mature and are functional. When encapsulated in synthetic hydrogel, EVCs respond to matrix cues and self-assembled to form three-dimensional EVCs. Moreover, these EVCs respond to hypoxic microenvironment and undergo vasculogenesis to form complex 3D networks.
THREE-DIMENSIONAL VASCULAR NETWORK ASSEMBLY FROM INDUCED PLURIPOTENT STEM CELLS
申请人：THE JOHNS HOPKINS UNIVERSITY
公开号：US20180216063A1
公开（公告）日：2018-08-02
Early vascular cells (EVCs), including endothelial cells and pericytes, are generated from hiPSCs. Unlike the isolated endothelial progenitor cells, the differentiated ECs mature and are functional. When encapsulated in synthetic hydrogel, EVCs respond to matrix cues and self-assembled to form three-dimensional EVCs. Moreover, these EVCs respond to hypoxic microenvironment and undergo vasculogenesis to form complex 3D networks.
MATERIALS AND METHODS FOR SUPPRESSING AND/OR TREATING BACTERIAL INFECTIONS AND RELATED SYMPTOMS
申请人：Indiana University Research and Technology Corporation
公开号：US20190038648A1
公开（公告）日：2019-02-07
Various aspects and embodiments disclosed herein relate generally to the modelling, treatment, reducing resistence to the treatment, prevention, and diagnosis of diseases/symptoms induced by infectious bacteria. Embodiments include methods of treating a bacterial infection, comprising the steps of: providing to a patient diagnosed with staphylococcal infection at least one therapeutically effective dose of a compound having an anti-virulence effect.
COMPOSITIONS AND METHODS FOR USE OF EFLORNITHINE AND DERIVATIVES AND ANALOGS THEREOF TO TREAT CANCERS, INCLUDING GLIOMAS
申请人：Orbus Therapeutics, Inc.
公开号：US20190133985A1
公开（公告）日：2019-05-09
Eflornithine is an agent that can be used to treat glioma, especially glioma of WHO Grade II or Grade III such as anaplastic glioma. Eflornithine can suppress or prevent mutations in glioma which can cause the glioma to progress to a higher grade. Compositions and methods can include eflornithine or a derivative or analog of eflornithine, together with other agents such as conventional anti-neoplastic agents for treatment of glioma, inhibitors of polyamine transport, polyamine analogs, or S-adenosylmethionine decarboxylase inhibitors. Eflornithine or derivatives or analogs thereof can also be used to treat a range of non-glioma malignancies, including both malignancies of the central nervous system and other malignancies.
