Novel (sulfated) thyroid hormone transporters in the solute carrier 22 family

Objective: Thyroid hormone (TH) transport represents a critical first step in governing intracellular TH regulation. It is still unknown whether the full repertoire of TH transporters has been identified. Members of the solute carrier (SLC) 22 family have substrates in common with the known TH transporters of the organic anion-transporting peptide family. Therefore, we screened the SLC22 family for TH transporters Methods: Uptake of 1 nM of iodothyronines or sulfated iodothyronines in COS1 cells expressing SLC22 proteins was performed. Results: We first tested 25 mouse (m) SLC22 proteins for TH uptake and fo und that the majority of the organic anion transporter (OAT) clade were capable of 3,3’,5-triiodothyronine and/or thyroxine (T4) transport. Based on phylogenetic tree analysis of the mouse and human (h) SLC22 family, we selected eight hSLC22s that grouped with the newly identified mouse TH transporters. Of thes e, four tested positive for uptake of one or more substrates, particularly hSLC22A11 showed robust (3-fold over control) uptake of T4. Uptake of sulfated iodothyronines was strongly (up to 17-fold) induced by some SLC22s, most notably SLC22A8, hSLC22A9, mSLC22A27 and mSLC22A29. Finally, the zebrafish orthologues of SLC22A6/8 drOat x and drSlc22a6l also transported almost all (sulfated) iodothyronines tested. The OAT inhibitors lesinurad and probenecid inhibited most SLC22 proteins. Conclusions: Our results demonstrated that members of the OAT clade of the SLC22 family constitute a novel, evolutionary conserved group of transporters for (sulfated) iodothyronines. Future studies should reveal the relevance of these transporters in TH homeostasis and physiology

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

The One Year Determinants of Patients Which Show The Cardiovascular Mortality, Who were Hospitalized for Acute Decompense Heart Failure

29th Turkish Cardiology Congress of the Turkish-Society-of-Cardiology (TSC) with International Participation -- OCT 26-29, 2013 -- Antalya, TURKEYWOS: 000329858400254Turkish Soc Cardio

The One Year Determinants of Patients Which Show The Cardiovascular Mortality, Who were Hospitalized for Acute Decompense Heart Failure

29th Turkish Cardiology Congress of the Turkish-Society-of-Cardiology (TSC) with International Participation -- OCT 26-29, 2013 -- Antalya, TURKEYWOS: 000329858400254Turkish Soc Cardio

THE EFFECTS OF CREATINE LONG-TERM SUPPLEMENTATION ON MUSCLE MORPHOLOGY AND SWIMMING PERFORMANCE IN RATS

Creatine (Cr) has been shown to increase the total muscle mass. The purpose of this study was to investigate the effect of Cr supplementation on muscle morphology and swimming performance, using an animal model. Each rat was subjected to exercise 15-minute period daily for the 12 weeks. The rats were randomly divided into four groups: no Cr supplementation (CON), no Cr supplementation and incomplete food intake (lacking lysine and methionine in diet for rats) (INCO), Cr supplementation 1 g·kg-1·day-1 (CREAT-I) and Cr supplementation 2 g·kg-1·day-1 (CREAT-II). Three months later, all groups adult rats exercised in swimming pool chambers. Swimming time was recorded as minute for each rat. Following swimming performance period, the animals were killed by cervical dislocation and the gastrocnemius and diaphragm muscles were dissected. Serial slices of 5-7 μm were allocated paraffin wax and histochemical staining procedure of cross-sections was carried out with heamatoxylin-eosin technics. All groups gained body weight at the end of 12 weeks but there was no statistical difference among them. Swimming time values were statistical difference between CREAT-II and CON group as well as between CREAT-I and CON group (p < 0.05). In the INCO group was determined increased connective tissue cell of the muscle sample. In contrast, in the CREAT-I and CREAT-II group, the basic histological changes were large-scale muscle fibers and hypertrophic muscle cells. These results suggest that long-term creatine supplementation increased the number of muscle fibers and enhanced endurance swimming performance in rat

The sympathetic skin response habituation in sedentary subjects and sportsmen

The aim of the present study was to investigate the habituation rates of the sympathetic skin response (SSR) in sedentary subjects and trained sportsmen. A total of 52 voluntary male students (30 sedentary subjects and 22 trained sportsmen) participated in the experiment. SSR was recorded with the contralateral electrical stimulation of the ulnar nerve (of the upper extremities). In order to initiate the SSRs, 16 square-wave consecutive electrical shock stimuli were presented to each subject over the left ulnar nerve. In 52 subjects, 16 stimuli were applied at random time intervals (20-50 s). In sedentary subjects, the mean amplitude of the SSRs decreased from 4.83 +/- 0.36 mV at the first stimulus, to 0.80 +/- 0.12 mV at the 16th stimulus. In trained sportsmen, the mean amplitude of the SSRs decreased from 3.95 +/- 0.51 mV at the first stimulus, to 0.80 +/- 0.17 mV at the 16th stimulus. In the sedentary subjects, at the S1-S9 stimuli, the mean amplitudes of SSRs were higher than those of trained sportsmen. Depending upon these findings we can say that the trained sportsmen showed a more rapid habituation than sedentary subjects. In these processes, changes of amplitude and latency values reflect changes in amount of neuronal activation. Amplitude reflects the amount of neuronal activation, which is concerned with number of neuronal populations. Neuroplasticity, known as the habituation of the brain, is the adaptation of autonomic nervous system, which can be reflected by SSRs

Calcium antagonists, digoxin, calcaemia and anaemia in heart failure.

WOS: 000412521200040Objective: To reveal that Calcium Antagonist (CA) use is associated with lower haemoglobin (Hb) and digoxin use is associated with higher Hb in Heart Failure (HF). Method: 223 chronic HF patients in acute decompensation phase were included in the study. Patients with comorbidities leading to anemia and those receiving blood transfusion or antianaemic treatment were excluded. Patients were classified into two groups as anemic and non-anemic groups. Two groups were compared retrospectively with demographics, clinical findings, medication use, echocardiography findings, complete blood count and biochemistry. Different independent variables between two groups were subjected to Multivariate Binary Logistic Regression Analysis (MBLRA) under the dependent variable anemia. Multivariable linear Regression Analysis (RA) was also performed with the dependent variable of Hb. Results: MBLRA results showed that anemia was seen less frequently in digoxin users, whereas it was more frequent in the following conditions: CA use, chronic renal failure, lower AST, lower LDL cholesterol, lower triglyceride, lower Transferring Saturation Rate (TSR). RA results also showed that lower LDL cholesterol, lower eGFR, lower transferrin saturation rate, lower corrected calcium, female gender and CA use were associated with lower Hb; whereas, digoxin use was associated with higher Hb. Conclusions: Haemoglobin levels were found higher in digoxin users. CA use, lower corrected calcium and lower AST were associated with lower Hb in heart failure. These findings have not been reported so far

Antivirals and the Potential Benefits of Orally Inhaled Drug Administration in COVID-19 Treatment.

Coronavirus Disease 2019 (COVID-19) pandemic has been on the agenda of humanity for more than 2 years. In the meantime, the pandemic has caused economic shutdowns, halt of daily lives and global mobility, overcrowding of the healthcare systems, panic, and worse, more than 6 million deaths. Today, there is still no specific therapy for COVID-19. Research focuses on repurposing of antiviral drugs that are licensed or currently in the research phase, with a known systemic safety profile. However, local safety profile should also be evaluated depending on the new indication, administration route and dosage form. Additionally, various vaccines have been developed. But the causative virus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has undergone multiple variations, too. The premise that vaccines may suffice to eradicate new and all variants is unreliable, as they are based on earlier versions of the virus. Therefore, a specific medication therapy for COVID-19 is crucial and needed in order to prevent severe complications of the disease. Even though there is no specific drug that inhibits the replication of the disease-causing virus, among the current treatment options, systemic antivirals are the most medically appropriate. As SARS-CoV-2 directly targets the lungs and initiates lung damage, treating COVID-19 with inhalants can offer many advantages over the enteral/parenteral administration. Inhaled drug delivery provides higher drug concentration, specifically in the pulmonary system. This enables the reduction of systemic side effects and produces a rapid clinical response. In this article, the most frequently (systemically) used antiviral compounds are reviewed including Remdesivir, Favipiravir, Molnupiravir, Lopinavir-Ritonavir, Umifenovir, Chloroquine, Hydroxychloroquine and Heparin. A comprehensive literature search was conducted to provide insight into the potential inhaled use of these antiviral drugs and the current studies on inhalation therapy for COVID-19 was presented. A brief evaluation was also made on the use of inhaler devices in the treatment of COVID-19. Inhaled antivirals paired with suitable inhaler devices should be considered for COVID-19 treatment options

Rapid adsorptive removal of naphthalene from water using graphene nanoplatelet/MIL-101 (Cr) nanocomposite

© 2017 Elsevier B.V.The study of the adsorption equilibria of naphthalene onto graphene nanoplatelet supported MIL-101 composite material (GNP/MIL-101) has been conducted. In the experimental context of this study, firstly GNP/MIL-101 was synthesized by applying hydrothermal method and characterized via FTIR, XRD, SEM, TEM and surface area analyses. The effects of GNP/MIL-101 amount, temperature and initial naphthalene concentration on the adsorption process have been investigated. Results show that the maximum removal of naphthalene was obtained as about 93% by 0.075 g GNP/MIL-101 at 298 K. The isothermal data were fitted to linear and non-linear Langmuir, Freundlich, and Temkin adsorption isotherm models and the kinetic data were fitted to Elovich and other kinetic models. Adsorption depended on initial naphthalene concentration at investigated various temperatures (298, 308, 318 K) significantly. The temperature dependence of adsorption process is associated with the changes in several thermodynamic parameters such as standard free energy (ΔG°), enthalpy (ΔH°) and entropy (ΔS°)