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Changes in the cuff pressure in neonates in the absence of nitrous oxide
No full textBackground: Changes in the pressure of cuffed neonatal size tracheal tubes (TT) during anaesthesia without nitrous oxide are not well described. We determined whether the cuff pressure changes over time in neonates under general anaesthesia without nitrous oxide. Methods: The airways of thirty neonates were secured with a high volume low pressure cuffed TT for meningocele surgery. The cuff was manually inflated until there was no audible leak and maintained at 10-15 cm H2O throughout by monitoring the pressure continuously with both a manometer and a pressure transducer. At baseline, the cuff pressure was assessed in the supine and then prone positions. During surgery, if the pressure exceeded 15 cm H2O, the cuff was deflated to < 15 cm H2O and if it was < 10 cm H2O, the cuff was inflated to 10-15 cm H2O. The time interval between corrections and the number of corrections were recorded. Results: The cuff pressures in 18 neonates (60%) required correction during surgery. The cuff pressure exceeded 15 cm H2O in nine neonates (30%) and was corrected. The cuff pressures in 13 neonates were less than 10 cm H2O and required correction. The gender, weight, height, and duration of anaesthesia did not differ significantly be-tween neonates who required correction of the cuff pressure and those who did not. Mean cuff pressures were similar at 15, 45, and 75 minutes of anaesthesia. Conclusions: In 60% of neonates undergoing surgery in the prone position under general anaesthesia without nitrous oxide, the cuff pressure exceeded 15 cm H2O. In such cases, cuff pressure should be monitored continuously throughout the surgery
INCIDENCE OF ANTERIOR UVEITIS IN AXIAL SPONDYLOARTHRITIS DURING SECUKINUMAB TREATMENT: TWO YEARS REAL LIFE EXPERIENCE FROM TURKBIO REGISTRY
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Cardiac effects of dapagliflozin in diabetic rats with subacute exposure
No full textBackground and Aims: Dapagliflozin (DAPA) is a sodium-glucose co-transporter 2 (SGLT2) inhibitor used for the treatment of type 2 diabetes mellitus (T2DM) as a monotherapy or combination therapy with other antidiabetic medicines. The Food and Drug Administration (FDA) recently approved DAPA to minimize the risk of hospitalization due to heart failure in patients with T2DM because of its antihypertensive and antihyperglycemic activities. However, further study of DAPA is necessary to ensure the safety of patients. Methods: T2DM was induced by streptozotocin (STZ) injection (35 mg/kg b.w. i.p.) in male rats that were fed a high-fat diet for two weeks before STZ injection. The diabetic rats were exposed to 10 mg/kg DAPA by oral gavage during sub-acute treat- ment. Total cholesterol levels and oxidative stress parameters were evaluated. Heart tissues were histologically examined, and cardiac troponin T (cTnT) levels were measured. Results: DAPA has the potential to inhibit diabetes-induced oxidative stress and morphologic damage to heart tissue, and increased cTnT levels of the heart, which is important for cardiac contractility. Conclusion: DAPA might have a protective effect on the heart at a 10 mg/kg oral dose; however, further experimental and clinical studies are required to clarify the cardio-protective potential of DAPA
Cardio-protective effect of dapagliflozin against doxorubicin induced cardiomyopathy in rats
No full textOBJECTIVE: Cancer is the second most common non-communicable disease group in the world and its frequency is increasing. In parallel, side effects of drugs used in cancer treatment are frequently encountered. Doxorubicin (DOX) is one of the most effective multi-purpose anticancer drugs. However, its use is significantly limited due to the risk of cardiotoxicity. Sodium-glucose cotransporter-2 inhibitors are a group of antidiabetic drugs that have been shown to reduce cardiovascular events. Our aim is to examine the preventive effect of dapagliflozin on DOX-induced cardiac damage. SUBJECTS AND METHODS: We used 30 albino rats. 20 of 30 rats were administered doxorubicin for cardiomyopathy model. The rats in the DOX arm were divided into two groups: those given penicillin and placebo. After the rats were terminated, tissues were prepared for histopathological and immunohistochemical examination. TNF-alpha, pro-BNP, troponin T and plasma FGF-21 levels were also measured in plasma. RESULTS: The mean concentrations of cTnT and pro-BNP in the plasma of the DOX treated rats demonstrated a significantly higher value compared to the control group. Treatment with dapagliflozin caused a significant reduction in plasma cTnT, pro-BNP and TNF-alpha levels concentrations compared to the DOX control group (p < 0.001). The group of rats treated with dapagliflozin was effective in significantly decreasing the FGF-21 concentration and the percentage of fibronectin immunoexpression compared to the DOX control group (p < 0.0001). CONCLUSIONS: This study revealed, for the first time, that dapagliflozin can improve DOX-induced cardiac dysfunction and pathological changes in non-diabetic rats. This result has shown that dapaglifozin, may be promising in terms of preventing cardiac damage that may develop in cancer treatment.National Institutes of Health, NIHAll experiments were carried out according to the Guide for the Care and Use of Laboratory Animals, as confirmed by National Institute of Health (USA)
Mutation spectrum of congenital heart disease in a consanguineous Turkish population
No full textBackgrounds: While many studies agree that consanguinity increases the rate of congenital heart disease (CHD), few genome analyses have been conducted with consanguineous CHD cohorts. Methods: We recruited 73 CHD probands from consanguineous families in Turkey and used whole-exome sequencing (WES) to identify genetic lesions in these patients. Results: On average, each patient had 6.95 rare damaging homozygous variants, 0.68 of which are loss-of-function (LoF) variants. Seven patients (9.6%) carried damaging homozygous variants in five causal CHD genes. Six of those patients exhibited laterality defects (six HTX and one D-TGA). Three additional patients (4.1%) harbored other types of CHD-associated genomic alterations, which overall explained 13.7% (10/73) of the cohort. The contribution from recessive variants in our cohort is higher than 1.8% reported from a cohort of 2871 CHD subjects where 5.6% of subjects met the criteria for consanguinity. Conclusions: Our WES screen of a Turkish consanguineous population with structural CHD revealed its unique genetic architecture. Six of seven damaging homozygous variants in CHD causal genes occur in the setting of laterality defects implies a strong contribution from consanguinity to these defects specifically. Our study thus provided valuable information about the genetic landscape of CHD in consanguineous families in Turkey.Yale Center for Mendelian Genomics - National Human Genome Research Institute [UM1HG006504]; GSP Coordinating Center [U24 HG008956]; American Heart Association Predoctoral Fellowship [19PRE34380842]; National Heart, Lung, and Blood InstituteThis work is supported by The Yale Center for Mendelian Genomics (UM1HG006504) which is funded by the National Human Genome Research Institute and National Heart, Lung, and Blood Institute. The GSP Coordinating Center (U24 HG008956) contributed to cross--program scientific initiatives and provided logistical and general study coordination. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. W.D. is supported by the American Heart Association Predoctoral Fellowship (19PRE34380842
Histone deacetylase inhibitor givinostat has ameliorative effect in the colitis model
No full textPurpose: To investigate the effect of givinostat treatment in acetic acid-induced ulcerative colitis model in rats. Methods: Thirty male Wistar albino rats were used. Rats were randomly divided into three equal groups, and colitis was induced on 20 rats by rectal administration of %4 solutions of acetic acid. Twenty rats with colitis were randomly divided into two groups. %0.9 NaCl (saline) solution was administered intraperitoneally to the first group of rats (saline group, n=10) at the dose of 1 mL/kg/day. Givinostat was administered intraperitoneally to the second group rats (Givinostat group, n=10) at the dose of 5 mg/kg/day. Samples were collected for biochemical analysis. Colon was removed for histopathological and biochemical examinations. Results: Plasma tumor necrosis factor-alpha (TNF-alpha), pentraxin-3 (PTX-3), and malondialdehyde levels were significantly decreased in the givinostat group compared to the saline group (p<0.05, p<0.001, and p<0.001 respectively; p<0.001, p<0.001, and p<0.001, respectively). Colon TNF-alpha and prostaglandin F2 alpha (PGF-2) levels were significantly decreased (p<0.05, and p<0.001, respectively). The givinostat group had a significantly lower histologic score than saline group (p<0.001, and p<0.001, respectively). Conclusion: Givinostat, a good protector and regenerator of tissue and an anti-inflammatory agent, may be involved in the treatment of colitis in the future
Main Outcomes of the DIYAL-TR Study: Regional Differences of Mortality and Morbidity in Chronic Hemodialysis Patients
No full textObjective: Variations in care at national or global level may have an impact on the prognosis of patients on chronic hemodialysis. We aimed to describe regional differences in all-cause mortality or cardiovascular morbidity in chronic hemodialysis patients in Turkey. Methods: We enrolled 2461 patients who were initiated chronic hemodialysis in 93 centers in Turkey between January 27, 2017, and February 09, 2018. We included 2-year follow-up data of 1877 patients in this prospective study. The primary outcome, the rate of composite endpoint of all-cause mortality or cardiovascular morbidity, was compared between geographical regions. Secondary outcomes were the rates of hospitalization and infections. Results: In total, 552 patients (29.4%) developed the primary outcome. The highest and lowest rates of primary outcome occurred in the Mediterranean (34.5%) and Southeastern (26.5%) & Central Anatolian regions (26.5%), respectively, with no significant differences across regions (P =.82). Hospitalization events were detected in 377 patients (20.1%). The highest rate of hospitalization was detected in the Black Sea region (33.8%), and the lowest (7.6%) in the Southeastern region. The regions did not differ in hospitalization rates (P =.88). Infections occurred in 11.3% (n = 212) of the patients. The highest and lowest rates of infections occurred in the Aegean (18.2%) and the Southeastern (2.9%) regions, respectively. We detected significant difference between geographic regions (P =.02). Conclusions: Our study showed that almost 3 in every 10 chronic hemodialysis patients reached the primary endpoint of all-cause mortality/cardiovascular morbidity during the 2 years of follow-up. The occurrence of this outcome does not seem to exhibit geographical variation across the country.Amgen TurkeyThis study was supported by Amgen Turkey
The Anti-Seizure Effect of Liraglutide on Ptz-Induced Convulsions Through its Anti-Oxidant and Anti-Inflammatory Properties
No full textEpilepsy is a prevalent and frequently devastating neurological disorder defined by recurring spontaneous seizures caused by aberrant electrical activity in the brain. Over ten million people worldwide suffer from drug-resistant epilepsy. This severe condition requires novel treatment approaches. Both oxidative and nitrosative stress are thought to have a role in the etiology of epilepsy. Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that is used to treat type-2 diabetes mellitus. According to recent studies, Liraglutide also shows neuroprotective properties, improving memory retention and total hippocampus pyramidal neuronal population in mice. The purpose of this investigation was to determine the anti-seizure and anti-oxidative effects of liraglutide in a pentylenetetrazole (PTZ)-induced rat model of epilepsy. 48 rats were randomly assigned to two groups: those who had electroencephalography (EEG) recordings and those who underwent behavioral assessment. Rats received either intraperitoneal (IP) liraglutide at two different dosages (3–6 mg/kg) or a placebo, followed by pentylenetetrazole (IP). To determine if liraglutide has anti-seizure characteristics, we examined seizure activity in rats using EEG, the Racine convulsion scale (RCS), the time of first myoclonic jerk (FMJ), and MDA, SOD, TNF-α, IL-1β and GAD-67 levels. The mean EEG spike wave percentage score was reduced from 75.8% (placebo) to 59.4% (lower-dose) and 41.5% (higher-dose). FMJ had increased from a mean of 70.6 s (placebo) to 181.2 s (lower-dose) and 205.2 s (higher-dose). RCS was reduced from a mean of 5.5 (placebo) to 2.7 (lower-dose) and 2.4 (higher-dose). Liraglutide (3 and 6 mg/kg i.p.) successfully decreased the spike percentages and RCS associated with PTZ induced epilepsy, as well as considerably decreased MDA, TNF-α, IL-1β and elevated SOD, GAD-67 levels in rat brain. Liraglutide significantly decreased seizure activity at both dosages when compared to control, most likely due to its anti-oxidant and anti-inflammatory properties. The potential clinical role of liraglutide as an anti-seizure medication should be further explored. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature
The relationship between clinical parameters and hepatocyte growth factor/c-Met levels in the sperm of infertile males
No full textObjective: Hepatocyte growth factor is a pleiotropic cytokine with potent mitogenic activity in many organs and tissues. The receptor for hepatocyte growth factor is c-Met, a transmembrane glycoprotein with tyrosine kinase activity. We investigated the relationships between hepatocyte growth factor and c-Met expression levels on sperm motility and male infertility. Methods: The study was designed as a prospective cohort, single-center clinical trial and was conducted between March 2015 and June 2016. The control group consisted of 31 healthy male volunteers with children, while the study group consisted of 61 men who were diagnosed with male infertility after presenting to the In Vitro Fertilization Unit of our Institute. All participants in the study were aged 18-60 years. Sperm samples were taken from each participant and divided in two. The fresh sample was examined immediately for expression of c-Met, while the other was stored frozen and evaluated later for hepatocyte growth factor. Primary outcome measures were the levels of hepatocyte growth factor and c-Met expression, while secondary outcome measures were the correlation of these levels with sperm count, morphology and motility. Results: The c-Met expression level in the control group (26.53 +/- 3.50, 19.43-32.73) was significantly lower than in the infertile group (27.95 +/- 2.86, 21.58-33.07) (p = 0.039). HGF expression was also significantly lower in the control group (3.25 +/- 1.76, 0.83-8.25) than in the infertile group (4.87 +/- 4.11, 1.01-21.58) (p = 0.043). In the overall group, c-Met expression showed a positive correlation with sperm motility percentage and a negative correlation with sperm count and sperm morphology percentage. Conclusions: The c-Met receptor and its ligand, hepatocyte growth factor, appear to be fundamental regulators of spermatogenesis, sperm motility and fertilization capacity
Antifibrotic preventive effect of polyethylene glycol (PEG) 3350 in methotrexate-induced hepatoxicity model
No full textPurpose: Liver damage caused by drugs and other chemicals accounts for about 5% of all cases. Methotrexate (MTX), a folic acid analogue, is a first-line synthetic antimetabolite agent routinely used in the treatment of rheumatoid arthritis and other autoimmune and chronic inflammatory diseases. Polyethylene glycol (PEG) has antioxidant activity. In this study, we evaluated biochemically and histopathologically the antifibrotic effect of PEG 3350 administered intraperitoneally to prevent methotrexate-induced liver damage in rats. Methods: A total of 30 male rats including 10 rats was given no drugs (normal group), and 20 rats received single-dose 20 mg/kg MTX for induced liver injury in this study. MTX was given to 20 rats, which were divided in two groups. Group 1 rats was given PEG 30 mg/kg/day (Merck) intraperitoneally, and Group 2 rats % 0.9 NaCl saline 1 mL/kg/day intraperitoneally daily for two weeks. Results: Transforming growth factor beta (TGF-beta), plasma malondialdehyde (MDA), liver MDA, serum tumour necrosis factor alpha (TNF-alpha), alanine aminotransferase and plasma pentraxin-3 levels and, according to tissue histopathology, hepatocyte necrosis, fibrosis and cellular infiltration were significantly better in MTX+PEG group than in MTX+saline group. Conclusion: PEG 3350 is a hope for toxic hepatitis due to other causes, since liver damage occurs through oxidative stress and cell damage, similar to all toxic drugs