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Nonsteroidal Anti-inflammatory Drugs-induced Failure of Lower Esophageal and Pyloric Sphincter and Counteraction of Sphincters Failure with Stable Gastric Pentadecapeptide BPC 157 in rats
No full textThe sphincters failure is a part of NSAIDs-toxicity that can be accordingly counteracted. We used a safe stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419), LD1 not achieved, since successful in inflammatory bowel disease trials, and counteracts esophagitis, sphincters failure, gastrointestinal ulcer and skin ulcer, external and internal fistulas in rats, and particularly counteracts all NSAIDs-lesions. We assessed lower esophageal sphincter and pyloric sphincter pressure (cmH2O) in rats treated with various NSAIDs regimens, at corresponding time points, known to produce stomach, small intestine lesions, hepatotoxicity and encephalopathy. Assessment was after diclofenac (12.5 mg/kg, 40 mg/kg intraperitoneal challenge), ibuprofen (400 mg/day/kg intraperitoneally for 4 weeks), paracetamol (5.0 g/kg intraperitoneal challenge), aspirin (400 mg/kg intraperitoneally or intragastrically), celecoxib (0.5 mg/kg, 1.0 mg/kg intraperitoneally). BPC 157 (10 μg/kg, 10 ng/kg) was given immediately after NSAIDs (intraperitoneally or intragastrically) or given in drinking water. Regularly, in all control NSAIDs fall of pressure occurred in both sphincters rapidly and then persisted. By contrast, in all NSAIDs-rats that received BPC 157, initial fall of pressure was minimized and pressure values restored to normal values. All tested NSAIDs decrease pressure in both sphincters, whilst BPC 157 counteracts their effects and restored both sphincters function
Serumska vrijednost osteoprotegerina u bolesnika s kalcificirajućom aortnom stenozom u ovisnosti o zatajenju srca
No full textThe aim of the study was to assess the role of serum osteoprotegerin (OPG) as a biomarker in patients with aortic valve stenosis (AS) in relation to heart failure and symptomatic status. This was a case control study, which included 51 patients with AS and 39 control subjects. At the time of study enrolment, detailed medical history was obtained and all subjects underwent physical examination, chest x-ray and echocardiography. OPG levels were measured in all subjects, and serum N-terminal of the pro b-type natriuretic peptide (NT pro BNP) levels were determined in patients with AS. Serum OPG levels were elevated in patients with AS compared to control subjects (p=0.001). Pa-tients with heart failure due to AS had elevated serum OPG levels in comparison to patients without heart failure (p=0.001). A significant correlation between OPG and symptomatic status was observed in all patients with AS (p<0.001), however, it was not the case in patients without heart failure (p=0.425). There was a positive correlation between OPG and NT pro BNP concentrations with objective signs of heart failure on chest x-ray (p<0.001). Negative correlation of OPG concentrations with aortic valve area was present (p<0.040), as well as with left ventricular ejection fraction (p<0.001). Serum OPG could be a valuable biomarker in the evaluation of severity of calcified AS and serve as an additional indicator besides clinical presentation and echocardiography in the assessment of surgical treatment or aortic valve replacement.Cilj ove studije bio je ocijeniti ulogu osteoprotegerina (OPG) kao biljega u bolesnika sa stenozom aortnog srčanog za-liska u odnosu na prisutne simptome kao i stupanj srčanog zatajenja. U studiju je bio uključen 51 bolesnik s aortnom steno-zom (AS) i 39 kontrolnih ispitanika. Prije uključenja u studiju uzeta je detaljna anamneza, učinjen je fizikalni pregled, ren-tgenska snimka srca i pluća te ehokardiografija. OPG je određen u svih ispitanika, a N-terminalni nastavak pro b-tipa natriu-retskog peptida (NT pro BNP) bio je određen u bolesnika s AS. OPG je bio povišen u bolesnika s AS u odnosu na kontrolne ispitanike (p=0,001). Bolesnici sa srčanim zatajenjem zbog AS imali su povišene razine OPG-a u odnosu na bolesnike bez srčanog zatajenja (p=0,001). Značajna korelacija između OPG-a i simptomatskog statusa bila je zapažena u svih bolesnika s AS (p<0,001), ali to nije bio slučaj u bolesnika bez srčanog zatajenja (p=0.425). Zabilježena je i pozitivna korelacija između koncentracije OPG-a i NT pro BNP-a s objektivnim znakovima srčanog zatajenja na rentgenskoj snimci srca i pluća (p<0,001). Također je opažena negativna korelacija OPG-a i areje aortnog zaliska (p<0,040) te istisne frakcije lijeve klijetke (p<0,001). OPG bi mogao predstavljati vrijedan biljeg u procjeni težine kalcificirane AS te bi mogao poslužiti kao dodatni indikator prilikom odlučivanja o kirurškom liječenju ili zamjeni aortnog zaliska, naravno, uz kliničku prezentaciju i ehokardiografiju
Učinci tjelesne aktivnosti na kroničnu subkliničku sustavnu upalu
No full textChronic subclinical systemic inflammation (CSSI) is a pathogenic event and a common risk factor for many noncommunicable diseases like atherosclerosis, metabolic syndrome, cardiovascular disease, insulin resistance and type 2 diabetes, cancer, and obstructive lung disease. On the other hand, regular physical activity has been found to reduce this risk. Many studies of different design were conducted to assess the association between inflammatory mediators as markers of CSSI and regular physical activity. The aim of this review was to present the current level of evidence and understanding of potential mechanisms by which physical activity reduces inflammatory mediators involved in CSSI and the types of physical activity required for the expected effect. We have found that observational studies consistently report a positive association between regular physical activity and lower CSSI, but the design of these studies does not allow to infer a causal relationship. Interventional studies, in contrast, were not consistent about the causal relationship between regular physical activity and lower CSSI. The problem in interpreting these results lies in significant differences between these interventional studies in their design, sample size, study population, and intervention itself (intensity and extent, follow up, weight loss). We can conclude that the scientific community has to invest a significant effort into high-quality interventional trials focused on finding the type, intensity, and extent of physical activity that would produce the most favourable effect on CSSI.Kronične nezarazne bolesti najznačajniji su javnozdravstveni problem. Kronična subklinička upala kao osnovni patološki supstrat zajednički je rizični čimbenik za većinu tih bolesti i stanja, kao što su arterioskleroza, metabolički sindrom, kardiovaskularne bolesti, rezistencija na inzulin i šećerna bolest tipa 2, novotvorine, opstruktivne plućne bolesti i mnoge druge. Nasuprot tomu, utvrđeno je da je redovita tjelesna aktivnost protektivni čimbenik u spomenutim bolestima. Provedene su mnoge studije različitoga dizajna s ciljem razotkrivanja povezanosti između kronične subkliničke upale i upalnih medijatora i redovite tjelesne aktivnosti. Cilj je ovog pregleda bio predočiti trenutačnu razinu dokaza te poimanja potencijalnih mehanizama u podlozi smanjenja kronične subkliničke upale kao posljedice redovite tjelesne aktivnosti, uključenih medijatora upale te oblika tjelesne aktivnosti potrebnih kako bi se postigao očekivani učinak. Utvrdili smo da su studije povezanosti predočile konzistentne dokaze u korist pozitivne povezanosti između redovite tjelesne aktivnosti i smanjenja kronične subkliničke upale. Dizajn tih studija ne dopušta zaključke o uzročno-posljedičnoj povezanosti ispitivanih fenomena. S druge strane, rezultati intervencijskih studija nisu konzistentni. Problem pri interpretaciji tih rezultata prouzročen je značajnom heterogenošću u dizajnu provedenih intervencijskih studija vezano uz veličinu uzorka, tip ispitanika te uz oblik intervencije (intenzitet i ekstenzitet tjelesne aktivnosti, trajanje intervencije, udruženost s gubitkom tjelesne mase). Na temelju trenutačne razine dokaza možemo zaključiti da je potrebno provesti više kvalitetnih intervencijskih studija radi definiranja tipa, intenziteta i ekstenziteta tjelesne aktivnosti koja će imati najznačajniji utjecaj na smanjenje kronične subkliničke upale
Iskra Guidelines on Diagnostics and Treatment of Prostatitis – Croatian National Guidelines
No full textSmjernice se odnose na klasifikaciju, dijagnostiku i liječenje sindroma prostatitisa. Njihov su cilj standardizacija, izjednačavanje i optimalizacija dijagnostike, liječenja i praćenja bolesnika s prostatitisom koji će dovesti do poboljšanja kvalitete zdravstvene zaštite ovih bolesnika te promovirati racionalnu potrošnju antibiotika. Namijenjene su ponajprije liječnicima opće prakse i specijalistima koji rade u primarnoj zdravstvenoj zaštiti i bolnicama. Ministarstvo zdravstva Republike Hrvatske (RH) imenovalo je članove Radne grupe za izradu smjernica namijenjenih dijagnostici i liječenju prostatitisa. Smjernice se temelje na dokazima iz sistematski pregledane literature, na lokalnim podacima o osjetljivosti bakterija na antibiotike, na postojećim kliničkim protokolima za dijagnostiku i liječenje prostatitisa, kao i prijedlozima i komentarima kolega liječnika. One su putem tečajeva trajne edukacije široko predstavljene liječnicima obiteljske medicine te specijalistima koji rade u primarnoj zdravstvenoj zaštiti i bolnicama – urolozima, infektolozima, mikrobiolozima i nefrolozima. Završnu verziju smjernica pregledali su i prihvatili članovi Interdisciplinarne sekcije za kontrolu rezistencije na antibiotike. U smjernicama su predstavljene kliničke upute radi standardizacije postupaka i kriterija za postavljanje dijagnoze i liječenje bolesnika s prostatitisom u RH.These guidelines refer to classification, diagnostics and treatment of prostatitis syndrome. The aim of these guidelines is the standardization, harmonization and optimization of diagnostics, treatment and monitoring of patients with prostatitis that would lead to improved quality of health care for these patients and promote rational use of antibiotics. The guidelines are primarily intended for general practitioners and specialists working in primary health care and hospitals. The members of the Working Group (WG) for the development of guidelines on diagnostics and treatment of prostatitis were appointed by the Croatian Ministry of Health. The evidence for these guidelines was identified by systematic review of the literature, local antibiotic resistance data, existing clinical protocols for diagnostics and treatment of prostatitis, as well as suggestions and comments from colleagues physicians. Through continuing medical education courses, the guidelines were widely presented to family medicine physicians and specialists working in primary health care and hospitals – urologists, infectious disease specialists, microbiologists and nephrologists. The final version of the guidelines was reviewed and approved by members of the Intersectoral Coordination Mechanism for the Control of Antimicrobial Resistance (ISKRA). These guidelines also present clinical instructions aimed at standardizing the procedures and criteria for diagnosis and treatment of patients with prostatitis in Croatia
Cancer patients follow-up - Croatian society for medical oncology clinical guidelines part IV : planocellular head and neck cancer, oesophageal cancer, gastric cancer, colorectal cancer.
No full textLiječenje onkoloških bolesnika mora se temeljiti na multidisciplinarnom pristupu, a provodi se u specijaliziranim onkološkim centrima. Nakon završetka specifičnog onkološkog liječenja daljnje praćenje uglavnom provode onkolozi, ali je uloga liječnika primarne zdravstvene zaštite (PZZ) sve važnija i potrebno ju je jasno definirati. Trenutačno većina preporuka za praćenje nije temeljena na prospektivnim studijama, već se zasniva na stručnim mišljenjima pojedinih onkoloških centara ili specijalista. Hrvatsko društvo za internističku onkologiju (HDIO) ovim preporukama želi standardizirati i racionalizirati dijagnostičke postupke u praćenju onkoloških bolesnika, nakon završetka primarnog liječenja, u bolesnika s planocelularnim rakom glave i vrata, rakom jednjaka, rakom želuca te rakom debelog i završnog crijeva.Treatment of oncological patients must be based upon multidisciplinary approach, and takes place in specialized oncological centers. By the end of a specifi c oncological treatment further follow-up is being managed mostly by the oncologists, but the role of the general practitioners becomes more important every day and therefore should be precisely defi ned. Nowadays, most of the existing follow-up guidelines are not being based on prospective studies, yet on the expert’s opinion of a precise oncological center or specialists. The aim of the Croatian Society of Medical Oncology (CSMO) with these recommendations is to standardize and rationalize the diagnostic procedures’ algorithm in follow–up of oncological patients after primary treatment, in patients with planocellular head and neck cancer, oesophageal cancer, gastric cancer and colorectal cancer
The Effect of Ambient Noise in the NICU on Cerebral Oxygenation in Preterm Neonates on High Flow Oxygen Therapy
No full textIn this early pilot study, we sought to determine if the alteration in these physiologic efects in premature infants in response to ambient noise in the NICU could be assessed evaluating cerebral blood saturation. Tree premature infants, on high fow
nasal cannula oxygen support (HFNC), at less than 34 weeks of gestation were included in the study. Tree variables were
used to evaluate sound levels due to AAP and EPA guidelines; Leq,1h, L10,1h and Lmax,1min. All of the patients studied were found to be exposed to statistically signifcant noise levels (above recommendation) throughout all of the time periods measured. Noise levels were found to be similarly elevated during the 1 am and 3 pm time periods as well, though not as much as compared to the 7 am measure. A statistically signifcant diference was found within every patient's rSO2 levels in both hemispheres, but also in the absolute diferences of rSO2. Positive signifcant statistical correlations were found between the average rSO2 and Leq,1h (ρ=0.14), Lmax,1min (ρ=0.18), L10,1h (ρ=0.15). Signifcant negative correlations were found between the absolute diference levels and Lmax,1min (ρ=-0.3), and L10,1h (ρ=-0.18) This data highlights the need for further study as to the potential impact of noise on the cerebral physiology of premature infants. Further research is needed to assess the potential long-term side efects of environmental noise on the premature infant’s brain
Hyperbaric Oxygenation and 20-hydroxyeicosatetreanoic acid Inhibition Reduce Stroke Volume in Female Diabetic Sprague-Dawley rats
No full textWhat is the central question of this study? Is there a beneficial effect and what are the mechanisms of acute and multiple hyperbaric oxygenation (HBO2 ) exposures on the outcome of cerebral tissue injury induced by a transient middle cerebral artery occlusion model in diabetic female rats? Are 20-hydroxyeicosatetreanoic acid and epoxyeicosatrienoic acids involved? What is the main finding and its importance? Equal reduction of cortical and total infarct size in rats treated with HBO2 and HET0016 (20-hydroxyeicosatetreanoic acid production inhibitor) and significant mRNA upregulation of epoxyeicosatrienoic acid-producing enzymes (Cyp2J3 and Cyp2C11) in treated groups suggest that HBO2 and HET0016 are highly effective stroke treatments and that cytochrome P450 metabolites are involved in this therapeutic effect. We evaluated the effects of acute and repetitive hyperbaric oxygenation (HBO2 ), 20-hydroxyeicosatetreanoic acid (20-HETE) inhibition by N-hydroxy-N'-(4-butyl-2methylphenyl)-formamidine (HET0016) and their combination on experimental stroke outcomes. Streptozotocin-induced type 1 diabetic Sprague-Dawley female rats (n = 42; n = 7 per group), were subjected to 30 min of transient middle cerebral artery occlusion (t-MCAO)-reperfusion and divided into the following groups: (1) control group, without treatment; and groups exposed to: (2) HBO2 ; (3) multiple HBO2 (HBO2 immediately and second exposure 12 h after t-MCAO); (4) HET0016 pretreatment (1 mg kg-1 , 3 days before t-MCAO) combined with HBO2 after t-MCAO; (5) HET0016 treatment (1 h before, during and for 6 h after t-MCAO); and (6) HET0016 treatment followed by HBO2 after t-MCAO. Messenger RNA expression of CYP2J3, CYP2C11, CYP4A1, endothelial nitric oxide synthase and epoxide hydrolase 2 was determined by real-time qPCR. Cortical infarct size and total infarct size were equally and significantly reduced in HBO2 - and HET0016-treated rats. Combined treatment with HET0016 and HBO2 provided no significant additive effect compared with HET0016 treatment only. Messenger RNA of Cyp2J3 was significantly increased in all study groups, and mRNA of Cyp2C11 was significantly increased in the multiple HBO2 group and the HET0016 treatment followed by HBO2 group, compared with the control group. Expression of endothelial nitric oxide synthase was significantly increased after HBO2 treatments, and expression of epoxide hydrolase 2 was increased in all groups compared with the control group. In diabetic female Sprague-Dawley rats, HBO2 and HET0016 are highly effective stroke treatments, suggesting the involvement of cytochrome P450 metabolites and the NO pathway in this therapeutic effect
Coronary Microvascular Dysfunction in Diabetes Mellitus
No full textThe significance, mechanisms and consequences of coronary microvascular dysfunction associated with diabetes mellitus are topics into which we have insufficient insight at this time. It is widely recognized that endothelial dysfunction that is caused by diabetes in various vascular beds contributes to a wide range of complications and exerts unfavorable effects on microcirculatory regulation. The coronary microcirculation is precisely regulated through a number of interconnected physiological processes with the purpose of matching local blood flow to myocardial metabolic demands. Dysregulation of this network might contribute to varying degrees of pathological consequences. This review discusses the most important findings regarding coronary microvascular dysfunction in diabetes from pre-clinical and clinical perspectives
The Added Value of Exhaled Breath Temperature in Respiratory Medicine
No full textRecognition of the huge economic burden chronic respiratory diseases pose for society motivated fundamental and clinical research leading to insight into the role of airway inflammation in various disease entities and their phenotypes. However, no easy, cheap and patient-friendly methods to assess it have found a place in routine clinical practice. Measurement of exhaled breath temperature (EBT) has been suggested as a non-invasive method to detect inflammatory processes in the airways as a result of increased blood flow within the airway walls. As EBT values are within a narrow range, the thermometers designed for the purpose of assessing it need to be precise and very sensitive. EBT increases linearly over the pediatric age range and seems to be influenced by gender, but not by height and body weight. In non-smoking individuals with no history of respiratory disease EBT has a natural circadian peak about noon and increases with food intake and physical exercise. When interpreting EBT in subjects with alleged airway pathology, the possibilities of tissue destruction (chronic obstructive pulmonary disease, cystic fibrosis) or excessive bronchial obstruction and air trapping (severe asthma) need to be considered, as these conditions drive (force) EBT down. A prominent advantage of the method is to assess EBT when patients are in a steady state of their disease and to use this 'personal best' to monitor them and guide their treatment. Individual devices outfitted with microprocessors and memory have been created, which can be used for personalized monitoring and disease management by telemedicine
Warfarin and Flavonoids do not Share the Same Binding Region in Binding to the IIA Subdomain of Human Serum Albumin
No full textHuman serum albumin (HSA) binds a variety of xenobiotics, including flavonoids and warfarin. The binding of another ligand to the IIA binding site on HSA can cause warfarin displacement and potentially the elevation of its free concentration in blood. Studies dealing with flavonoid-induced warfarin displacement from HSA provided controversial results: estimated risk of displacement ranged from none to serious. To resolve these controversies, in vitro study of simultaneous binding of warfarin and eight different flavonoid aglycons and glycosides to HSA was carried out by fluorescence spectroscopy as well as molecular docking. Results show that warfarin and flavonoids do not share the same binding region in binding to HSA. Interactions were only observed at high warfarin concentrations not attainable under recommended dosing regimes. Docking experiments show that flavonoid aglycons and glycosides do not bind at warfarin high affinity sites, but rather to different regions within the IIA HSA subdomain. Thus, the risk of clinically significant warfarin-flavonoid interaction in binding to HSA should be regarded as negligible