Parasitology Research - To counteract host immunity, Cryptosporidium parvum has evolved multiple strategies to suppress host antimicrobial defense. One such strategy is to reduce the production of... 相似文献
Background Previously, dapagliflozin was limited to patients with an estimated glomerular filtration rate (eGFR)?≥?60 mL/min/1.73 m2, while empagliflozin can be used for those with an eGFR?≥?45 mL/min/1.73 m2. Therefore dapagliflozin was switched to empagliflozin in many patients when eGFR decreased. However, the clinical efficacy and safety of these switcfhes are not clear. Objective In this study, we compared the efficacy and renal safety between patients switching from dapagliflozin to empagliflozin in patients. Setting This is a retrospective study of adult patients (aged?≥?20 years) who had attended the Kaohsiung Medical University Hospital. Method This retrospective observational study included patients who were switched from dapagliflozin to empagliflozin. To assess the effect of other hypoglycemic drugs on efficacy, the types and dose alterations of other hypoglycemic drugs were classified on the defined daily dose (DDD). Main outcome measure The primary outcome measure was the change in hemoglobin A1c (HbA1c) level after 6 months. Patients with HbA1c levels at or lower than the baseline value after 6 months were defined as effective and patients with levels higher than the baseline were defined as invalid. Safety was evaluated by comparing the difference of eGFR between the baseline value and 6 months after treatment. Results Overall, 111 patients were enrolled in the study. Six months after switching from dapagliflozin to empagliflozin, HbA1c significantly reduced, with no statistically significant difference observed in eGFR. In our study, 78 patients were assigned to the effective group (70.3%) and 33 patients were invalid (29.7%). When the other hypoglycemic drugs were grouped by total dosage, fasting plasma glucose and HbA1c only decreased significantly in the "DDD decrease" and "DDD increase" groups. Conclusion Our study showed that switching from dapagliflozin to empagliflozin in patients with type 2 diabetes was effective for blood glucose maintenance and caused no significant changes in renal function. In addition, compared to similar sodium-glucose co-transporter-2 inhibitors, other hypoglycemic drugs may be factors that influence the efficacy of sugar-lowering treatments.
Methadone (Mtd) is a widely used opioid drug associated with the side effect of hyperprolactinemia. The mechanism of how Mtd induces prolactin secretion remains unclear. The effects of Mtd and its two main metabolites (EDDP: (±)-2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium percholarate and EMDP: 2-ethyl-5-methyl-3,3-dipnehyl-1-pyrroline) on ion currents were investigated in GH? pituitary tumor cells. Hyperpolarization-elicited K+ currents in GH? cells bathed in a high-K(+), Ca(2+)-free solution were studied to evaluate the effects of Mtd and other related compounds on the ether-à-go-go-related-gene (erg) K(+) current (I(K(erg))). Mtd suppressed the amplitude of I(K(erg)) in a concentration-dependent manner with an IC(50) value of 10.4 μM. With the aid of a minimal binding scheme, the inhibitory action of Mtd on I(K(erg)) was estimated with a dissociation constant of 8.2 μM. Mtd tended to increase the rate of I(K(erg)) deactivation in a voltage-dependent fashion. EDDP (10 μM) had no effect on I(K(erg)), while EMDP (10μM) slightly suppressed it. In GH? cells incubated with naloxone (30 μM), the Mtd-induced inhibition of I(K(erg)) remained unaltered. Under cell-attached voltage-clamp recordings, Mtd increased the frequency of spontaneous action currents with no change in current amplitude. Similarly, Mtd can suppress I(K(erg)) in differentiated NG108-15 cells; dynorphin A(1-13) did not reverse Mtd-induced inhibition of I(K(erg)). This study shows that Mtd has a depressant effect on I(K(erg)), and suggests its ability to affect membrane excitability and prolactin secretion. The cyclization of Mtd, in which EDDP and EMDP are formed, tends to be critical in removal of the Mtd binding to erg K+ channel. 相似文献
Dang-Gui-Shao-Yao-San (DGSYS) is a mixture of medicinal herbs, which has long been used in traditional Chinese medicine for treating anemia and ovulary disorders. Its preparation comprises Angelicae sinensis (Oliv.) Diels, Ligustucum chuanxiong Hort, Paeonia lactiflora pall, Poria cocos (Schw.) Wolf, Atractylodis macrocephala Koidz and Alisma orientalis (Sam.) Juzep. The present study examined the anti-superoxide formation, free radical scavenging and anti-lipid peroxidation activities of DGSYS by xanthine oxidase inhibition, cytochrome C system with superoxide anion released by the fMLP or PMA activating pathway in human neutrophils, and FeCl2 ascorbic acid-induced lipid peroxidation effects on lipids in rat liver homogenate, respectively. DGSYS showed anti-superoxide formation and free radical scavenging activity in a concentration-dependent manner. It also inhibited PMA- but not fMLP-induced superoxide anion released from human neutrophils. These antioxidant actions of DGSYS showed beneficial cytoprotective effects against lipid peroxidation in rat liver homogenate, human platelet aggregation induced by arachidonic acid (AA) and adenosine diphosphate (ADP) and mitomycin C-mediated hemolytic in human erythrocytes. 相似文献
The ionic mechanisms and cytoprotective activities of 4-piperidinomethyl-2-isopropyl-5-methylphenol (THPI), an analogue of thymol, were investigated in HL-60 granulocytes and in human erythrocytes, respectively. THPI inhibited K+ outward current (I(K)) in a concentration-dependent manner in HL-60 leukocytes, with an IC50 value of 4 microM. Neither iberiotoxin (200 nM) nor paxilline (1 microM) suppressed the amplitude of I(K), whereas clotrimazole (5 microM) significantly inhibited it. In the inside-out configuration of single channel recordings, application of THPI (5 microM) into the bath medium did not alter the single-channel conductance of intermediate-conductance Ca2+-activated K+ (IK(Ca)) channels (i.e K(Ca)3.1 channels), but it suppressed the channel activity significantly. THPI-induced inhibition of IK(Ca) channels was reversed by a further application of 1-ethyl-2-benzimidazolinone (10 microM). THPI-induced reduction in IK(Ca)-channel activity in these cells was primarily due to a decrease in mean open time. These results provide direct evidence that THPI is capable of suppressing the activity of IK(Ca) channels in HL-60 cells. The antioxidant action of THPI also revealed a beneficial cytoprotective effect against mitomycin C-mediated haemolytic effect in human erythrocytes. The results of this study suggest that blockade of IK(Ca) channels and the membrane-protecting activity of THPI would combine to have beneficial effects in lessening the severity of haemolytic crisis and reducing anaemia in sickle cell disease. 相似文献
4-Piperidinomethyl-2-isopropyl-5-methylphenol (THPI) was synthesized by reaction of thymol with piperidine and formaldehyde. The biological effect of THPI on superoxide anion scavenging activity, antiplatelet activity and calcium current inhibition were investigated. THPI (50 microM) was shown to be a scavenger of superoxide radicals in human neutrophils stimulated with N-formyl-Met-Leu-Phe (66% inhibition). Since superoxide anions are essential for platelet aggregation and L-type Ca2+-channel activity, we further found that THPI inhibited platelet aggregation induced by arachidonic acid (IC50 46.80+/-6.88 microM). The effect of THPI on Ca2+ current in NG108-15 cells was investigated using the whole-cell voltage-clamp technique. THPI inhibited voltage-dependent L-type Ca2+ current (ICa, L). The IC50 value of THPI-induced inhibition of ICa, L was 3.60+/-0.81 microM. THPI caused no change in the overall shape of the current-voltage relationship of ICa, L. This indicates that THPI is an inhibitor of ICa, L in NG108-15 cells. Therefore, the channel-blocking properties of THPI may contribute to the underlying mechanism by which it affects neuronal or neuroendocrine function. Furthermore, no significant cytotoxic effects of THPI (0.3-50 microM) were observed in NG108-15 cells. The results indicate that THPI is a potential reactive oxygen species scavenger and may prevent platelet aggregation or inhibit L-type Ca2+-channel activity, possibly by scavenging reactive oxygen species. 相似文献