Pregnancy causes a multitude of metabolic changes within a woman’s body in order to provide the proper nutrients to the developing fetus. In women with diabetes type 1, type 2, and GDM （gestational diabetes mellitus...Pregnancy causes a multitude of metabolic changes within a woman’s body in order to provide the proper nutrients to the developing fetus. In women with diabetes type 1, type 2, and GDM （gestational diabetes mellitus） these metabolic perturbations must be treated distinctly and aggressively to optimize fetal development and health. Pre-gestational diabetes （either type 1 or type 2） has the potential to subject the developing fetus to abnormal maternal glucose levels resulting in problems with organogenesis producing congenital abnormalities or spontaneous abortion. Furthermore, gestational diabetes mellitus presents after organogenesis in the second part of pregnancy, therefore the major risk for the fetus is macrosomia. Although the goal for dietary therapy for each of these disorders is the same which is euglycaemia, the means to achieve it are very different and somewhat controversial. In the case of gestational diabetes, the main stay of therapy is medical nutritional therapy whereas in insulin requiring diabetes, dietary therapy is compensated with pre-meal insulin injections. The metabolic changes in normal pregnancy will be presented followed by the general guidelines for pregnancy. Fetal complications associated with inadequate nutrition or metabolic perturbation will be briefly explored, followed by issues and treatment for gestational diabetes mellitus, with emphasis on specific dietary therapies for GDM.展开更多
Buoyed by the discovery of small-molecule tyrosine kinase inhibitors(smTKIs),significant impact has been made in cancer chemotherapeutics.However,some of these agents still encounter off-target toxicities and suboptim...Buoyed by the discovery of small-molecule tyrosine kinase inhibitors(smTKIs),significant impact has been made in cancer chemotherapeutics.However,some of these agents still encounter off-target toxicities and suboptimal efficacies due to their inferior biopharmaceutical and/or pharmacokinetic properties.Almost all of these molecules exhibit significant inter-and intra-patient variations in plasma concentration-time profiles.Thus,therapeutic drug monitoring,dose adjustments and precision medicine are being contemplated by clinicians.Complex formulations or nanoformulation-based drug delivery systems offer promising approaches to provide drug encapsulation or spatiotemporal control over the release,overcoming the biopharmaceutical and pharmacokinetic limitations and improving the therapeutic outcomes.In this context,the present review comprehensively tabulates and critically analyzes all the relevant properties(T1/2,solubility,pKa,therapeutic index,IC50,metabolism etc.)of the approved smTKIs.A detailed appraisal is conducted on the advancements made in complex formulations of smTKIs,with a focus on strategies to enhance their pharmacokinetic profile,tumor targeting ability,and therapeutic efficacy.Various nanocarrier platforms,have been discussed,highlighting their unique features and potential applications in cancer therapy.Nanoformulations have been shown to improve bioavailability and reduce dosing frequency for several smTKIs in animal models.It is inferred that extensive efforts will be made in developing complex formulations of smTKIs in near future.The review concludes with key recommendations for the developing of smTKIs to facilitate early clinical translation.展开更多
文摘Pregnancy causes a multitude of metabolic changes within a woman’s body in order to provide the proper nutrients to the developing fetus. In women with diabetes type 1, type 2, and GDM （gestational diabetes mellitus） these metabolic perturbations must be treated distinctly and aggressively to optimize fetal development and health. Pre-gestational diabetes （either type 1 or type 2） has the potential to subject the developing fetus to abnormal maternal glucose levels resulting in problems with organogenesis producing congenital abnormalities or spontaneous abortion. Furthermore, gestational diabetes mellitus presents after organogenesis in the second part of pregnancy, therefore the major risk for the fetus is macrosomia. Although the goal for dietary therapy for each of these disorders is the same which is euglycaemia, the means to achieve it are very different and somewhat controversial. In the case of gestational diabetes, the main stay of therapy is medical nutritional therapy whereas in insulin requiring diabetes, dietary therapy is compensated with pre-meal insulin injections. The metabolic changes in normal pregnancy will be presented followed by the general guidelines for pregnancy. Fetal complications associated with inadequate nutrition or metabolic perturbation will be briefly explored, followed by issues and treatment for gestational diabetes mellitus, with emphasis on specific dietary therapies for GDM.
文摘Buoyed by the discovery of small-molecule tyrosine kinase inhibitors(smTKIs),significant impact has been made in cancer chemotherapeutics.However,some of these agents still encounter off-target toxicities and suboptimal efficacies due to their inferior biopharmaceutical and/or pharmacokinetic properties.Almost all of these molecules exhibit significant inter-and intra-patient variations in plasma concentration-time profiles.Thus,therapeutic drug monitoring,dose adjustments and precision medicine are being contemplated by clinicians.Complex formulations or nanoformulation-based drug delivery systems offer promising approaches to provide drug encapsulation or spatiotemporal control over the release,overcoming the biopharmaceutical and pharmacokinetic limitations and improving the therapeutic outcomes.In this context,the present review comprehensively tabulates and critically analyzes all the relevant properties(T1/2,solubility,pKa,therapeutic index,IC50,metabolism etc.)of the approved smTKIs.A detailed appraisal is conducted on the advancements made in complex formulations of smTKIs,with a focus on strategies to enhance their pharmacokinetic profile,tumor targeting ability,and therapeutic efficacy.Various nanocarrier platforms,have been discussed,highlighting their unique features and potential applications in cancer therapy.Nanoformulations have been shown to improve bioavailability and reduce dosing frequency for several smTKIs in animal models.It is inferred that extensive efforts will be made in developing complex formulations of smTKIs in near future.The review concludes with key recommendations for the developing of smTKIs to facilitate early clinical translation.
