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Jungi Hwang

and 6 more

DWP16001 is a novel sodium-glucose cotransporter-2 (SGLT2) inhibitor under development for the treatment of type 2 diabetes mellitus. This study was conducted to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of DWP16001 after single and multiple doses in healthy subjects. A randomized, double-blind, placebo- and active-controlled, single- and multiple-dose study was conducted. Twelve subjects in each dose group received a single dose (0.2, 0.5, 1.0, 2.0, or 5.0 mg) or multiple doses (0.1, 0.3, 0.5, 1.0, or 2.0 mg once daily for 15 consecutive days) of DWP16001, dapagliflozin 10 mg, or placebo, in a ratio of 8:2:2. Serial blood samples and interval urine samples were collected for PK and PD analyses. Safety and tolerability were assessed throughout the study period. A dose-dependent increase in urinary glucose excretion (UGE) was observed after a single dose, and the steady-state UGE was 50–60 g/day after multiple doses in the dose range of 0.3 – 2.0 mg. DWP16001 was rapidly absorbed with the time to peak plasma concentration of 1.0 – 3.0 hours, and eliminated with a mean elimination half-life of 13 - 29 hours. The systemic exposure of DWP16001 increased proportionally with the dose after multiple administrations in the range of 0.1 – 2.0 mg. DWP16001 was well tolerated in all dose groups. DWP16001 caused glucosuria in a dose-dependent manner, and systemic exposure was observed after multiple doses. DWP16001 was well tolerated up to 5.0 mg after a single oral dose and up to 2.0 mg after multiple oral administration

Gokcen Unal

and 8 more

Coronavirus disease 2019 (COVID-19) is a viral disease caused by a novel coronavirus that can lead to severe acute respiratory failure. Recent studies have shown that aggravating factors in the etiology of COVID-19 disease include genetic defects and autoantibodies against type 1 interferon. Mycobacterium tuberculosis is an immobile aerobic bacillus that causes tuberculosis disease. SARS-CoV-2 infection and immunosuppressive drugs may temporarily inhibit immunologic system, then may lead to active tuberculosis by reactivation or infection of M. tuberculosis. We aimed to show that there is a relationship between covid-19 infection and an increase in the number of tuberculosis patients. Eight patients diagnosed with tuberculosis in the Pediatric Pulmonology and Pediatric Infectious Diseases Clinics of Necmettin Erbakan University, Meram Medical Faculty between March 2020 and May 2021 were enrolled in this study. The presence of COVID-19 infection was confirmed by COVID-19 antibody test and patient’s detailed medical history. The patient with negative antibody test was also included in the study if other family members confirmed for COVID-19 infection by RT-PCR. We evaluated demographic data, laboratory findings, imaging tests and pathology results of all patients. The remarkable increase in the number of tuberculosis activation in the recent year suggests the role of COVID-19 infection. The pathologic structure of the virus may be responsible of the increase, although the mechanism is not fully understood. Further research should be done on this topic.

Yi-wei Yin

and 4 more

Background: Hepatic steatosis is associated with increased surgical complications in patients undergoing bariatric surgery. The aim of this study was to evaluate the effect of phentermine in reducing hepatic steatosis, adipose tissue and surgical complications in patients undergoing bariatric surgery. Methods: This study is a two-arm, double-blind, randomized, controlled pilot trial of 64 adult subjects with BMI >35 kg/m2 selected for bariatric surgery randomized to phentermine 15 mg once daily for 8 week or placebo. Both groups adhered to a hypocaloric diet and individualized exercise program. The primary end point was the reduce frequency of hepatic steatosis measured by ultrasound and the reduce adipose tissue through fat mass in total kilograms or percentage. Key secondary points were the prevalence of surgical complications. Baseline and final biochemical parameters and blood pressure too were assessments. Results: Phentermine group the frequency of hepatic steatosis decreased 19%, and the percentage of patients with a normal ultrasound increased from 9% to 20% (p= 0.053). Likewise, the decrease in fat mass in kilograms was greater in the phentermine group (56.1 kg vs. 51.8 kg, p=0.02), and a significant decrease in the HOMA-IR index was observed regardless of weight loss. No differences in surgical complications were observed between groups. Phentermine was well tolerated; no differences were observed in the frequency of adverse events between the groups. Conclusions: Phentermine decreased the proportion of individuals with hepatic steatosis by 19%, promoted a greater loss of fat mass in kilograms, and decreased insulin resistance among candidates for bariatric surgery.

Sung-Min Cho

and 5 more

Background: Patients with venoarterial extracorporeal membrane oxygenation (VA-ECMO) are at risk of cerebral reperfusion injury after prolonged hypoperfusion and immediate restoration of systemic blood flow. We aimed to examine the impact of mild hypothermia during the first 24 hours post-ECMO on neurological outcome in VA-ECMO patients. Methods: This was a retrospective study of adult VA-ECMO patients from a tertiary care center. Mild hypothermia was defined as 32-36°C during the first 24 hours post-ECMO. Primary outcome was good neurological function at discharge measured by a modified Rankin Scale ≤3. Multivariable logistic regression analysis was performed for primary outcome adjusting for pre-specified covariates. Results: Overall, 128 consecutive patients with VA-ECMO support (median age: 60 years and 63% males) were included. Within the first 24 hours of VA-ECMO cannulation, we found a median of 71 readings per patient (interquartile range 45-88). Eighty-eight patients (68.8%) experienced mild hypothermia within the first 24 hours while 18 of those 88 patients (14.2%) had a mean temperature<36°C. ECMO indications included post-cardiotomy shock (39.8%), cardiac arrest (29.7%), and cardiogenic shock (26.6%). Duration of mild hypothermia, but not mean temperature, was independently associated with increased odds of good neurological outcome at discharge (Odds Ratio [OR]=1.16, 95% Confidence Interval [CI]=1.04-1.31, p=0.01) after adjusting for age, severity of illness, post-ECMO systemic hemorrhage, post-cardiotomy shock, acute brain injury, and mean 24-hour PaO 2. Neither duration of mild hypothermia (OR=0.93, CI=0.84-1.03, p=0.17) nor mean temperature (OR=0.78, CI=0.29-2.08, p=0.62) was significantly associated with mortality. Similarly, duration of mild hypothermia (p=0.47) and mean 24-hour temperature (p=0.76) were not significantly associated with frequency of systemic hemorrhages. Conclusions: In this single center study, longer duration of mild hypothermia during the first 24 hours of ECMO support was significantly associated with improved neurological outcome. Mild hypothermia was not associated with an increased risk of systemic hemorrhage or improved survival.

Xue Chen

and 7 more

Background and Purpose: The current study investigated whether the manipulation of gut microbiome through treatment with an antibiotic cocktail can alter the bioavailability of clopidogrel active metabolite (Clop-AM) in T2DM rats. Experimental Approach: Control and T2DM rats were orally administered with either vehicle or an antibiotic cocktail containing ampicillin, neomycin, metronidazole, and vancomycin for 5 consecutive days. The levels of clopidogrel (Clop) and its metabolites were measured by LC-MS/MS. Biochemical parameters, liver microsome metabolism, mRNA, protein or activity of Clop- metabolizing enzymes and transporter, and 16S rRNA sequence of fecal samples were analyzed to explain any altered pharmacokinetic profile of Clop-AM. Key Results: Antibiotic administration markedly alleviated T2DM rats’ phenotypes including hyperglycemia, hyperlipidemia, insulin resistance, liver dysfunction and inflammation. Meanwhile, the reduced systemic exposure of Clop-AM in T2DM rats as compared to control rats was significantly reversed after antibiotic treatment, accompanied with the decreased expression of P-glycoprotein (P-gp) in small intestine, suggesting P-gp-based Clop absorption might be promoted, consequently making more Clop available for Clop-AM formation. Interestingly, fecal microbiome analysis exhibited the reduced microbial amount and the altered microbial composition in antibiotic-treated T2DM rats. Especially, there was an inconsistent change of P-gp levels between T2DM rats and SW480 cells after antibiotic treatment, suggesting antibiotic-induced microbiome depletion, not the direct role of antibiotics is associated with the enhanced Clop-AM plasma exposure in T2DM rats. Conclusion and Implication: The findings show that gut microbiota modulation is an effective therapeutic strategy to enhance Clop-AM generation under T2DM conditions.

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