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Presječna studija dinamike temperature izdaha nakon popušene cigarete i njezina povezanost s promjenama plućne funkcije u pušača prediktivnima za rizik od KOPB-a
Exhaled breath temperature (EBT) is a biomarker of inflammation and vascularity of the airways already shown to predict incident COPD. This cross-sectional study was aimed to assess the potential of EBT in identifying “healthy” smokers susceptible to cigarette smoke toxicity of the airways and to the risk of developing COPD by analysing the dynamics of EBT after smoking a cigarette and its associations with their demographics (age, smoking burden) and lung function. The study included 55 current smokers of both sexes, 29–62 years of age, with median smoking exposure of 15 (10–71.8) pack-years. EBT was measured at baseline and 5, 15, 30, 45, and 60 min after smoking a single cigarette. Lung function was measured with spirometry followed by a bronchodilator test. To compare changes in EBT between repeated measurements we used the analysis of variance and the area under the curve (EBTAUC) as a dependent variable. Multivariate regression analysis was used to look for associations with patient characteristics and lung function in particular. The average (±SD) baseline EBT was 33.42±1.50 °C. The highest significant increase to 33.84 (1.25) °C was recorded 5 min after the cigarette was smoked (p=0.003), and it took one hour for it to return to the baseline. EBTAUC showed significant repeatability (ICC=0.85, p<0.001) and was significantly associated with age, body mass index, number of cigarettes smoked a day, baseline EBT, and baseline FEF75 (R2=0.39, p<0.001 for the model). Our results suggest that EBT after smoking a single cigarette could be used as early risk predictor of changes associated with chronic cigarette smoke exposure.Temperatura izdaha (EBT) biomarker je upale i vaskularizacije dišnih putova za koji je utvrđeno da može predvidjeti nastanak KOPB-a. Cilj ove presječne studije bio je procijeniti potencijal EBT-a u identifikaciji “zdravih” pušača čiji su dišni putovi osjetljivi na toksični učinak duhanskoga dima uz rizik od nastanka KOPB-a. Taj se cilj planirao postići utvrđivanjem povezanosti dinamike EBT-a nakon popušene cigarete s demografskim karakteristikama (dob, spol, pušačka navika) i plućnom funkcijom ispitanika. U ispitivanje je bilo uključeno 55 aktivnih pušača obaju spolova u dobi od 29 do 62 godine, čiji je medijan izloženosti duhanskom dimu bio 15 (10 – 71,8) pušačkih godina (pack-years). EBT je mjeren na početku te 5, 15, 30, 45 i 60 minuta nakon popušene cigarete. Plućnu funkciju mjerili smo spirometrijski, uz susljedni bronhodilatacijski test. Za analizu dinamike EBT-a koristili smo se analizom varijance te smo izračunali površinu ispod krivulje u odnosu na početno mjerenje (EBTAUC) te EBTAUC upotrijebili kao zavisnu varijablu. Multivarijatna regresijska analiza korištena je za utvrđivanje povezanosti EBTAUC s karakteristikama ispitanika, posebice s plućnom funkcijom. Prosječni (±SD) izmjereni početni EBT bio je 33,42±1,50 °C, a najveće značajno izmjereno povećanje zabilježeno je 5 minuta nakon popušene cigarete (33,84 (1,25) °C, p=0,003). Bilo je potrebno 60 minuta kako bi se EBT vratio na početnu vrijednost. Utvrđena je značajna ponovljivost EBTAUC (ICC=0,85, p<0,001). Ispitivanjem je utvrđeno je da je EBTAUC značajno nezavisno povezan s dobi, indeksom tjelesne mase, brojem popušenih cigareta dnevno, početnim EBT-om te s početnim FEF75 (R2=0,39, p<0,001 za model). Rezultati ove studije sugeriraju da EBT nakon popušene cigarete može biti koristan kao rani prediktor rizika od promjena koje su povezane s kroničnom izloženosti duhanskom dimu
Inspiratory muscle strength affects anaerobic endurance in professional athletes
To the best of our knowledge, little is known about the role of respiratory muscle strength and endurance on athlete performance in anaerobic conditions of maximal exertion. The aim of this cross-sectional study was therefore to examine the association between the strength/endurance of inspiratory muscles in a group of 70 healthy male professional athletes (team sports) and their ventilatory and metabolic parameters at the anaerobic threshold (second ventilatory threshold; VT2) and beyond it at maximum load during the cardiopulmonary exercise test (CPET) on a treadmill. Ventilatory parameters at VT2, at maximal effort, and their differences were tested for association with inspiratory muscle strength (PImax) and endurance (Tlim), measured as time to maintain inspiration at or above 80% of PImax. The difference in end-tidal oxygen tension (ΔPETO2) between VT2 and maximal effort was significantly associated with resting heart rate (HR) and systolic blood pressure (BP), PImax, and lean body mass (LBM) (r2=0.26, p=0.016; multivariate regression analysis). The difference in carbon dioxide output (ΔVCO2) was significantly associated with body mass index (BMI), resting HR, systolic BP, and PImax (r2=0.25, p=0.022; multivariate regression analysis). Our findings suggest that it is the inspiratory muscle strength and not endurance that affects the performance of professional athletes and that it should be tested and trained systematically.Cilj ovog presječnog istraživanja, u kojem je sudjelovalo 70 zdravih muškaraca vrhunskih sportaša (momčadskih sportova) bio je ispitati povezanost snage/izdržljivosti inspiratorne muskulature i ventilacijskih i metaboličkih parametara na anaerobnom pragu (drugi ventilacijski prag; VT2) te nakon njega pri maksimalnom opterećenju tijekom kardiopulmonalnog testiranja na tekućoj traci (CPET). Ventilacijski parametri na VT2, pri maksimalnom naporu te njihova razlika testirani su na povezanost sa snagom inspiratorne muskulature (PImax) i izdržljivošću (Tlim), koja je izmjerena kao vrijeme tijekom kojega se zadržava ventilacija na ili iznad 80% PImax. Razlika tlaka kisika na kraju izdaha između VT2 i maksimalnog napora (ΔPETO2) značajno je bila povezana sa srčanom frekvencijom (HR) i sistoličkim krvnim tlakom (SBP) u mirovanju, s PImax i bezmasnom masom tijela (LBM) (r2=0,26, p=0,016; multivarijatna regresijska analiza). Razlika izdahnutog CO2 (ΔVCO2) značajno je bila povezana s indeksom tjelesne mase (BMI), HR-om i SBP-om u mirovanju te s PImax (r2=0,25, p=0,022; multivarijatna regresijska analiza). Rezultati ovog istraživanja upućuju na to da snaga, a ne izdržljivost inspiratorne muskulature značajno utječe na radni učinak (izvedbu) vrhunskih sportaša te da ju je potrebno sustavno mjeriti i trenirati
The Soluble Fms-like Tyrosin Kinase-1 (sFLT-1) to Placental Growth Factor (PIGF) Ratio as a Possible Indicator for the Severity of Preeclampsia - Single Institution Experience
Aim To investigate a potential of the clinical use of the soluble fms-like tyrosine kinase 1 (sFLT-1) to placental growth factor (PlGF) ratio from the perspective of a small hospital centre. Methods Maternal serum samples were analysed at 241/7-28 0/7, and 281/7-320/7 weeks of gestation. The level of sFLT-1 and PIGF was determined by immunoassay platform and used to calculate the sFLT-1/PIGF ratio in 35 pregnant women, and divided into subgroups according to preeclampsia occurrence at the time of delivery: preterm (≤37 weeks) or term (37-42 weeks'), and matched a control group. Results Patients in the preterm delivery group had a significantly higher incidence of intrauterine growth restriction, lower gestational age at the time of delivery, and lower infant birth weight compared to the other two groups. There was a negative correlation between the sFLT-1/PlGF ratio and GA and between the sFLT-1/ PlGF ratio and birth weight at the time of delivery. The value of the sFLT-1/PlGF ratio was significantly higher in the preterm delivery PE group. All the PE group pregnancies ended with caesarean delivery compared to 25% in the control group. However, none of the patients from the PE group had any of the possible complications of preeclampsia nor did they require additional therapy such as blood transfusion or additional non-standard hypertensive therapy. Conclusion The sFLT-1/PlGF ratio could be used as an indicator for the development and estimation of the severity of PE to provide objective evidence for the management of preeclampsia patients, and as a predictive marker of preeclampsia at low cost
Differential Expression of TFF1 and TFF3 in Patients Suffering from Chronic Rhinosinusitis with Nasal Polyposis
Trefoil family factor (TFF) proteins contribute to antimicrobial defense and the maintenance of sinonasal epithelial barrier integrity. Dysregulation of TFF expression may be involved in the development of chronic inflammation and tissue remodeling characteristically found in chronic rhinosinusitis with nasal polyposis (CRSwNP). Expressions of TFF1 and TFF3 were determined in specimens of middle nasal turbinate (MNT-0), bulla ethmoidalis (BE), and nasal polyps (NP) from CRSwNP patients (n = 29) and inferior nasal turbinate from a group of control patients (underwent nasal septoplasty, n = 25). An additional MNT sample was collected 6 months after functional endoscopic sinus surgery (FESS, MNT-6). TFF1 mRNA levels were significantly reduced in all specimens by approximately three- to five-fold, while TFF3 was increased in MNT-0, as compared with controls. Six months after surgery their levels were reversed to control values. CRSwNP patients with S. epidermidis isolated from sinus swabs showed upregulation of TFF3 in MNT and NP as compared with patients with sterile swabs. Target gene regulation was not affected by the presence of type 2 inflammation in patients with confirmed allergy. Results of this study imply participation of TFFs genes in the development of CRSwNP
Preživljenje do otpusta iz bolnice novorođenčadi vrlo niske porođajne težine u dvije hrvatske perinatalne regije: retrospektivna studija vremena i uzroka smrti
We investigated mortality, causes, timing and risk factors for death until hospital discharge in very-low-birth-weight (VLBW) infants born in two Croatian perinatal care regions. This retrospective study included 252 live born VLBW infants. The mortality rate until hospital discharge was 30.5% (77/252). VLBW in-fants who died had by 4 weeks lower gestational age (GA) than surviving infants (median GA, 25 vs. 29 weeks), lower birth weight (BW) (mean BW, 756.4 vs. 1126.4 g), lower 5-minute Apgar score (median 5 vs. 8) and were more often resuscitated at birth (41.6 vs. 19.4%; p12 hours to necrotizing enterocolitis.Istraživali smo smrtnost, uzroke, vrijeme i rizične čimbenike za smrt do otpusta iz bolnice u novorođenčadi vrlo niske porođajne težine (VNPT) rođene u dvije hrvatske perinatalne regije. Ova retrospektivna studija je uključila 252 živo-rođena novorođenčeta VNPT. Smrtnost do otpusta iz bolnice bila je 30.5% (77/252). Novorođenčad VNPT koja su umrla bila su 4 tjedna manje gestacijske dobi od novorođenčadi koja je preživjela (medijan gestacijske dobi 25 prema 29 tjedana; p12 sati glavni uzrok smrti je nekrotizirajući enterokolitis
Effect of Tff3 Deficiency and ER Stress in the Liver
Endoplasmic reticulum (ER) stress, a cellular condition caused by the accumulation of unfolded proteins inside the ER, has been recognized as a major pathological mechanism in a variety of conditions, including cancer, metabolic and neurodegenerative diseases. Trefoil factor family (TFFs) peptides are present in different epithelial organs, blood supply, neural tissues, as well as in the liver, and their deficiency has been linked to the ER function. Complete ablation of Tff3 expression is observed in steatosis, and as the most prominent change in the early phase of diabetes in multigenic mouse models of diabesity. To elucidate the role of Tff3 deficiency on different pathologically relevant pathways, we have developed a new congenic mouse model Tff3-/-/C57BL6/N from a mixed background strain (C57BL6/N /SV129) by using a speed congenics approach. Acute ER stress was evoked by tunicamycin treatment, and mice were sacrificed after 24 h. Afterwards the effect of Tff3 deficiency was evaluated with regard to the expression of relevant oxidative and ER stress genes, relevant proinflammatory cytokines/chemokines, and the global protein content. The most dramatic change was noticed at the level of inflammation-related genes, while markers for unfolded protein response were not significantly affected. Ultrastructural analysis confirmed that the size of lipid vacuoles was affected as well. Since the liver acts as an important metabolic and immunological organ, the influence of Tff3 deficiency and physiological function possibly reflects on the whole organism
Peptic Ulcer Disease: a Brief Review of Conventional Therapy and Herbal Treatment Options
Peptic ulcer is a chronic disease affecting up to 10% of the world's population. The formation of peptic ulcers depends on the presence of gastric juice pH and the decrease in mucosal defenses. Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (H. pylori) infection are the two major factors disrupting the mucosal resistance to injury. Conventional treatments of peptic ulcers, such as proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists, have demonstrated adverse effects, relapses, and various drug interactions. On the other hand, medicinal plants and their chemical compounds are useful in the prevention and treatment of numerous diseases. Hence, this review presents common medicinal plants that may be used for the treatment or prevention of peptic ulcers
Safety of the Radiofrequency Denervation for Chronic Pain Treatment - Single Centre Experience from Osijek University Hospital Centre
The Physiological Effect of n-3 Polyunsaturated Fatty Acids (n-3 PUFAs) Intake and Exercise on Hemorheology, Microvascular Function, and Physical Performance in Health and Cardiovascular Diseases; Is There an Interaction of Exercise and Dietary n-3 PUFA Intake?
Physical activity has a beneficial effect on systemic hemodynamics, physical strength, and cardiac function in cardiovascular (CV) patients. Potential beneficial effects of dietary intake of n-3 polyunsaturated fatty acids (n-3 PUFAs), such as α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid on hemorheology, vascular function, inflammation and potential to improve physical performance as well as other CV parameters are currently investigated. Recent meta-analysis suggests no effect of n-3 PUFA supplementation on CV function and outcomes of CV diseases. On the other hand, some studies support beneficial effects of n-3 PUFAs dietary intake on CV and muscular system, as well as on immune responses in healthy and in CV patients. Furthermore, the interaction of exercise and dietary n-3 PUFA intake is understudied. Supplementation of n-3 PUFAs has been shown to have antithrombotic effects (by decreasing blood viscosity, decreasing coagulation factor and PAI-1 levels and platelet aggregation/reactivity, enhancing fibrinolysis, but without effects on erythrocyte deformability). They decrease inflammation by decreasing IL-6, MCP-1, TNFα and hsCRP levels, expression of endothelial cell adhesion molecules and significantly affect blood composition of fatty acids. Treatment with n-3 PUFAs enhances brachial artery blood flow and conductance during exercise and enhances microvascular post-occlusive hyperemic response in healthy humans, however, the effects are unknown in cardiovascular patients. Supplementation of n-3 PUFAs may improve anaerobic endurance and may modulate oxygen consumption during intense exercise, may increase metabolic capacity, enhance endurance capacity delaying the onset of fatigue, and improving muscle hypertrophy and neuromuscular function in humans and animal models. In addition, n-3 PUFAs have anti-inflammatory and anti-nociceptive effects and may attenuate delayed-onset muscle soreness and muscle stiffness, and preserve joint mobility. On the other hand, effects of n-3 PUFAs were variably observed in men and women and they vary depending on dietary protocol, type of supplementation and type of sports activity undertaken, both in healthy and cardiovascular patients. In this review we will discuss the physiological effects of n-3 PUFA intake and exercise on hemorheology, microvascular function, immunomodulation and inflammation and physical performance in healthy persons and in cardiovascular diseases; elucidating if there is an interaction of exercise and diet
Targeting Burkitt Lymphoma with a Tumor Cell–specific Heptamethine Carbocyanine-cisplatin Conjugate
BACKGROUND: Burkitt lymphoma is a fast-growing mature B cell malignancy, whose genetic hallmark is translocation and activation of the c-myc gene. Prompt multiagent immunochemotherapy regimens can have favorable outcomes, but prognosis is poor in refractory or relapsed disease. We previously identified a novel family of near-infrared heptamethine carbocyanine fluorescent dyes (HMCD or DZ) with tumor-homing properties via organic anion-transporting peptides. These membrane carriers have uptake in tumor cells but not normal cells in cell culture, mouse and dog tumor models, patient-derived xenografts, and perfused kidney cancers in human patients.
METHODS: Here we report the cytotoxic effects of a synthesized conjugate of DZ with cisplatin (CIS) on B cell lymphoma CA46, Daudi, Namalwa, Raji, and Ramos cell lines in cell culture and in xenograft tumor formation. Impaired mitochondrial membrane permeability was examined as the mechanism of DZ-CIS-induced lymphoma cell death.
RESULTS: The new conjugate, DZ-CIS, is cytotoxic against Burkitt lymphoma cell lines and tumor models. DZ-CIS retains tumor-homing properties to mitochondrial and lysosomal compartments, does not accumulate in normal cells and tissues, and has no nephrotoxicity in mice. DZ-CIS accumulated in Burkitt lymphoma cells and tumors induces apoptosis and retards tumor cell growth in culture and xenograft tumor growth in mice.
CONCLUSION: DZ-CIS downregulated c-myc and overcame CIS resistance in myc-driven TP53-mutated aggressive B cell Burkitt lymphoma. We propose that DZ-CIS could be used to treat relapsed/refractory aggressive Burkitt lymphomas