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Farnesyltransferase Inhibitors: Current and Prospective Development for Hematologic Malignancies
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
In a phase I/II trial of tipifarnib, led by Gotlib (59), in a cohort of patients with CMML, atypical CML, and unclassifiable hybrid diseases, sustained reductions in the WBC were noted in 24% of patients, while an additional 41% experienced nonsustained reductions. No cytogenetic responses were noted, and no baseline Ras mutations were observed. Likewise, of 25 CMML patients treated with lonafarnib 200 to 300 mg BID continuously, eight (32%) achieved a clinical response (1 CR, 7 HI) (54). However, lonafarnib can induce hyperleukocytosis and pulmonary leukostatis consistent with a “leukemia differentiation syndrome” in 3 of 35 CMML patients, with an additional 12 patients exhibiting a less dramatic leukemoid response (60). The leukocytosis and accompanying respiratory distress occurred predominantly in patients with proliferative CMML and responded to steroids and lonafarnib discontinuation. The exacerbation of proliferation and release may relate to the ability of lonafarnib to modulate integrin activation and thus CMML cell adhesion to vascular endothelium and bone marrow stroma (61). No such syndrome has been detected with tipifarnib to date.
Chemistry and Isotopes of Iodine
Published in Erwin Regoeczi, Iodine-Labeled Plasma Proteins, 2019
Hydrogen iodide (HI) is a colorless gas that is decomposed by light. It is very soluble in H2O, and the resulting acid (hydriodic acid, HI) is the strongest among all hydrohalic acids. Hydriodic acid is used as a reducing agent. Since the preparation of this compound takes place under fairly drastic laboratory conditions,2 the chances of HI forming during protein iodination seem quite remote.
Principles of Radioiodination and Iodine-Labeled Tracers in Biomedical Investigation †
Published in Garimella V. S. Rayudu, Lelio G. Colombetti, Radiotracers for Medical Applications, 2019
Mrinal K. Dewanjee, Shyam A. Rao
The heterogeneous exchange reaction R–H + I–I* = R–I* + HI has a theoretical maximum of 50% utilization of iodine. In the presence of oxidizing agents such as iodic acid, persulfate, hydriodic acid, or alkaline medium, iodine is consumed and the iodination reaction proceeds to the right. Radioiodine solution for protein labeling should not contain any stabilizer (for example, a reducing agent like sodium bisulfite) because the reducing agent might consume the active species and reduce the yield of radioiodination. Reductant-free radioiodide is commercially available, or it can be produced readily by adding a small amount of iodide carrier and hydrogen peroxide, acidifying, and distilling the iodine into dilute alkali in a glove box or a well-ventilated hood.
HI-6-loaded PEGylated liposomes: an on-site first-aid strategy for acute organophosphorus agent poisoning
Published in Drug Delivery, 2023
Liao Shen, Yadan Zhang, Qimei Cai, Jun Yang, Yongan Wang, Dongqin Quan
Organophosphorus chemical nerve agents are the most toxic substances around the world. Their strong, fast neurotic toxicity makes it very difficult to prevent and cure. Therefore, on-site first-aid measures play an important role in improving the survival rate and recovery after intoxication. Oxime antidotes are among the therapeutic drug group that can effectively revive phosphorylated AChE and restore its original function. The common oxime antidotes include pralidoxime iodide, pyraloxime methylchloride, obidoxime, HI-6 and MMB-4. HI-6 has been proven to be an effective AChE reactivator with a wide spectrum of therapeutic activity, especially for soman, GF, and VR. However, pharmacokinetic studies have revealed rapid plasma clearance of HI-6, which means that HI-6 is not suitable for on-site first aid of OP poisoning as a one-shot injection. The slow intravenous infusion may maintain a stable drug concentration, but this method is difficult to achieve in the absence of adequate medical personnel and equipment, especially during war.
Predictive value of serum d -serine level for hearing impairment in uremic patients
Published in Renal Failure, 2023
Jiaqing Li, Dunlu Yuan, Qing Yang, Jingjing Huang, Zhu Zhou, Ruomei Li, Qing Li
The analysis of the influencing factors of HI in uremia revealed that the risk score of HI was Y = −1.485 + 2.089 × age + 2.013×d-serine − 1.548×l-serine. Hearing decreases with increasing age [28]. The level of d-serine in uremic patients with HI was significantly higher than that in uremic patients with normal hearing. The risk of HI in uremic patients with d-serine ≥10 μM was 5.63 times higher than in patients with d-serine <10 μM. Typically, this result should consider the putative bias factors caused by the small sample size in the study, prompting us to expand the sample size at the later stage. Serum l-serine is a protective factor for hearing, but the specific upstream and downstream mechanisms are yet unclear. Several studies have shown that l-serine can be converted to d-serine under the action of SR, and DAO accelerates the degradation of d-serine. Whether SR is overexpressed or DAO response is reduced in uremic patients, resulting in an increase in d-serine content, is yet to be elucidated.
Appraisal of heavy metal toxicity in surface water with human health risk by a novel approach: a study on an urban river in vicinity to industrial areas of Bangladesh
Published in Toxin Reviews, 2021
Ram Proshad, Saiful Islam, Tanmoy Roy Tusher, Dan Zhang, Sujan Khadka, Jianing Gao, Satyajit Kundu
Hazard index (HI) are the combined effect of exposed metals and metalloids. When considering the total exposure (HI) via oral and dermal contact, there was a chance of having non-cancer risk of all metals for male, female and children’s health. The HI acts as a conservative assessment tool to calculate high-end risk rather than low-end risk to protect the people (Qu ET AL. 2012). The HI value via oral exposure by male, female and children was found to be 4.17E + 00, 3.67E + 00 and 8.64E + 00, respectively; indicating non-carcinogenic effects is believed to occur (Table 7). Due to fishing, HI for male (2.21E + 00) and female (2.20E + 00) was found to be higher than 1 (HI > 1) indicating a chronic non-cancer effect is likely to occur and probability increases with the increase of HI values (Paustenbach 2015).