The vitamin D and microRNA (miR) systems may play a role in the pathogenesis of cardiometabolic disorders, including hypertension. The HYPODD study was a double-blind placebo-controlled trial aiming ...to assess the effects of cholecalciferol treatment in patients with well-controlled hypertension and hypovitaminosis D (25OHD levels < 50 nmol/L). In addition to this clinical trial, we also evaluated the effects of cholecalciferol and calcitriol treatment on miR-21 expression in vivo and in vitro, respectively. Changes in the cardiovascular risk profiles were evaluated in HYPODD patients treated with cholecalciferol (C-cohort) or with placebo (P-cohort). The miR-21circulating levels were measured in four C-cohort patients and five P-cohort patients. In vitro, the miR-21 levels were measured in HEK-293 cells treated with calcitriol or with ethanol vehicle control. Cholecalciferol treatment increased 25OHD levels and reduced parathormone, total cholesterol, and low-density lipoprotein cholesterol levels in C-cohort patients, whereas no significant changes in these parameters were observed in P-cohort patients. The miR-21 circulating levels did not change in the C- or the P-cohort patients upon treatment. Calcitriol treatment did not affect miR-21 levels in HEK-293 cells. In conclusion, hypovitaminosis D correction ameliorated the cardiovascular risk profiles in hypertensive patients treated with cholecalciferol but did not influence the miR-21 expression.
•Hydatid cyst from different intermediate host from Iraq were molecularly characterized.•High prevalence for G1 strain was reported in all hosts.•A G1 cox1 microvariant (Hap5) was common in sheep, ...cattle and human hosts.•Two new cox1 microvariants were described (Hap 7–8).
Cystic echinococcosis/hydatidosis is an important cosmopolitan zoonotic disease that causes large economic losses and human suffering. The larval stages of Echinococcus granulosus are the etiological agents of cystic echinococcosis that showed different genotypes in different regions in the world. The present study was aimed at the detection of E. granulosus strains circulating in two cities from north of Iraq (Kirkuk and Sulaimania). A total of 47 specimens of hydatid cysts were collected from patients and from different domestic intermediate hosts including cattle, sheep, goat and buffalo from slaughterhouses. Molecular characterization was performed by direct sequencing of the mitochondrial DNA (mtDNA) genes coding for the cytochrome c oxidase I (cox1) and the small subunit ribosomal RNA (rrnS). The results showed a high prevalence for the sheep strain (G1), an isolated finding of the buffalo strain (G3) and the presence of seven and three different microvariants for cox1 and rrnS, respectively. This is the first contribution on molecular genotyping of E. granulosus in Iraq with the observation of genotypes other than G1.
Effective control of tuberculosis (TB) includes discrimination of subjects with active TB from individuals with latent TB infection (LTBI). As distinct interferon (IFN)-y and interleukin (IL)-2 ...profiles of antigen-specific T-cells have been associated with different clinical stages and antigen loads in several viral and bacterial diseases, we analysed these cytokines in TB using a modified QuantiFERON-TB Gold In Tube test. Detection of IL-2 in addition to IFN-γ distinguishes not only Mycobacterium tuberculosis-infected subjects from healthy controls, but also individuals with LTBI from active TB patients. This may help to improve diagnostic tests for TB.
is a tapeworm whose life cycle includes dogs and other canines as final hosts, while domestic and wild ungulates act as intermediate hosts for the tissue-invading larval stage (metacestode).
has a ...worldwide geographical distribution. Protoscolices and rostellar hooks of
are useful for diagnosis and rostellar hook morphometric features may be useful to discriminate
and related species. The present study was aimed to determine a more suitable lytic solution and to obtain a clearest vision for performing morphometric studies on the rostellar hooks of
protoscolices. Five fertile hydatid cyst samples were collected from sheep in Kirkuk slaughterhouse, Iraq, during June of 2015. According to the results of the present study, proteinase-K lytic solution is the best approach in morphometric analysis to get a clear vision of rostellar hooks and a safer usage in comparison with solutions containing lactophenol (lactophenol, lactophenol blue).
ATPase (SERCA2a) pumps. Furthermore, we show that NO influences cardiac response to preload through S-nitrosylation of phospholamban
and consequent activation of SERCA2a. This suggests that in the ...fish heart NO modulates the Frank–Starling response through
a beat-to-beat regulation of calcium reuptake and thus of myocardial relaxation., we previously showed that an endogenous NO release affects the Frank–Starling response making the heart more sensitive to
preload. Using the same bioassay, we now demonstrate that this effect is confirmed in the presence of the exogenous NO donor, We propose that this mechanism represents an important evolutionary step for the stretch-induced intrinsic regulation of the
vertebrate heart, providing, at the same time, a stimulus for mammalian-oriented studies., Anguilla anguilla, -acetyl penicillamine, is independent from endocardial endothelium and guanylate cyclase/cGMP/protein kinase G and cAMP/protein
kinase A pathways, involves a PI(3)kinase-mediated activation of endothelial NO synthase and a modulation of the SR-CA, In the, in vitro, The Frank–Starling mechanism is a fundamental property of the vertebrate heart, which allows the myocardium to respond to
increased filling pressure with a more vigorous contraction of its lengthened fibres. In mammals, myocardial stretch increases
cardiac nitric oxide (NO) release from both vascular endothelium and cardiomyocytes. This facilitates myocardial relaxation
and ventricular diastolic distensibility, thus influencing the Frank–Starling mechanism., working heart of the eel
Using morphological and physiological approaches we provided, for the first time, a structural and functional characterization of Carassius auratus L. heart. Besides to the classical four chambers, ...i.e. sinus venosus, atrium, ventricle, bulbus, we described two distinct structures corresponding to the atrio-ventricular (AV) region and the conus arteriosus. The atrium is very large and highly trabeculated; the ventricle shows an outer compacta, vascularized by coronary vessels, and an inner spongiosa; the bulbus wall is characterized by a high elastin/collagen ratio, which makes it extremely compliant. Immunolocalization revealed a strong expression of activated “eNOS-like” isoforms both at coronary endothelium and, to a lesser extent, in the myocardiocytes and the endocardial endothelium (EE). The structural design of the heart appears to comply with its mechanical function. Using an in vitro working heart preparation, cardiac performance was evaluated at different filling and afterload pressures. The hearts were very sensitive to filling pressure increases. Maximum Stroke volume (SV=1.08±0.09mL/kg body mass) was obtained with an input pressure of 0.4kPa. The heart was not able to sustain afterload increases, values higher than 1.5kPa impairing its performance. These morpho-functional features are consistent with a volume pump mechanical performance.
Purpose
Obesity is the main feature of a complex illness known as metabolic syndrome. Anti-obesogenic therapies are often associated with side effects and represent a high cost in conventional ...pharmacological approaches. New strategies based on natural remedies are under continuous investigation.
Leopoldia comosa
(L.) Parl. (
L. comosa
) is a spontaneous plant with diuretic, anti-inflammatory and antioxidant properties. Recently, a hypoglycemic activity mediated by inhibition of carbohydrate digestion has been identified. The aim of this study was to evaluate the effects of a diet supplemented with
L. comosa
extracts on a rat model of diet-induced obesity.
Methods
Leopoldia comosa
bulb extracts were obtained using a dynamic extractor. Phytochemical properties and in vitro determination of the antioxidant activity and of the inhibitory effects on lipase and pancreatic amylase were performed. Rats were fed (12 weeks) a standard diet, or a high-fat diet (HFD), or an HFD plus
L. comosa
(20 or 60 mg/die) extracts. The metabolic and anthropometric parameters were recorded.
Results
Results indicated that
L. comosa
inhibited lipase and pancreatic amylase activities. In vivo data showed that the supplementation with both doses of
L. comosa
extracts counteracted the HFD-dependent effects. It reduced body weight, abdominal obesity and dyslipidemia, and improved glucose tolerance with a reduction of lipidic tissue hypertrophy and liver steatosis, as compared to HFD-fed rat. In liver,
L. comosa
reduced protein expression levels of PEPCK and G6Pase.
Conclusion
We suggest that
L. comosa
extracts prevent obesity-dependent metabolic disorders. This paves the way for their therapeutic application as a natural anti-obesity drug.
•Robust proton vs x-ray planning on free-breathing (FB) STAGE III NSCLC was tested.•A reduction of NTCP risk of pulmonary and cardiac toxicity was scored with protons.•A reduction in the dose to the ...immune system was observed with protons.•Robust optimization is an interesting and novel solution also for x-ray therapy.•Robust FB proton therapy could be an effective option for selected STAGE III NSCLC.
To assess the robustness and to define the dosimetric and NTCP advantages of pencil-beam-scanning proton therapy (PBSPT) compared with VMAT for unresectable Stage III non-small lung cancer (NSCLC) in the immunotherapy era.
10 patients were re-planned with VMAT and PBSPT using: 1) ITV-based robust optimization with 0.5 cm setup uncertainties and (for PBSPT) 3.5 % range uncertainties on free-breathing CT 2) CTV-based RO including all 4DCTs anatomies. Target coverage (TC), organs at risk dose and TC robustness (TCR), set at V95%, were compared. The NTCP risk for radiation pneumonitis (RP), 24-month mortality (24MM), G2 + acute esophageal toxicity (ET), the dose to the immune system (EDIC) and the left anterior descending (LAD) coronary artery V15 < 10 % were registered. Wilcoxon test was used.
Both PBSPT methods improved TC and TCR (p < 0.01). The mean lung dose and lung V20 were lower with PBSPT (p < 0.01). Median mean heart dose reduction with PBSPT was 8 Gy (p < 0.001). PT lowered median LAD V15 (p = 0.004).
ΔNTCP > 5 % with PBSPT was observed for two patients for RP and for five patients for 24 MM. ΔNTCP for ≥ G2 ET was not in favor of PBSPT for all patients. PBSPT halved median EDIC (4.9/5.1 Gy for ITV/CTV-based VMAT vs 2.3 Gy for both ITV/CTV-based PBSPT, p < 0.01).
PBSPT is a robust approach with significant dosimetric and NTCP advantages over VMAT; the EDIC reduction could allow for a better integration with immunotherapy. A clinical benefit for a subset of NSCLC patients is expected.
The teleostean Channichthyidae (icefish), endemic stenotherms of the Antarctic waters, perennially at or near freezing, represent a unique example of disaptation among adult vertebrates for their ...loss of functional traits, particularly hemoglobin (Hb) and, in some species, cardiac myoglobin (Mb), once considered to be essential-life oxygen-binding chromoproteins. Conceivably, this stably frigid, oxygen-rich habitat has permitted high tolerance of disaptation, followed by subsequent adaptive recovery based on gene expression reprogramming and compensatory responses, including an alternative cardio-circulatory design, Hb-free blood and Mb-free cardiac muscle. This review revisits the functional significance of the multilevel cardio-circulatory compensations (hypervolemia, near-zero hematocrit and low blood viscosity, large bore capillaries, increased vascularity with great capacitance, cardiomegaly with very large cardiac output, high blood flow with low systemic pressure and systemic resistance) that counteract the challenge of hypoxemic hypoxia by increasing peripheral oxygen transcellular movement for aerobic tissues, including the myocardium. Reconsidered in the context of recent knowledge on both polar cold adaptation and the new questions related to the advent of nitric oxide (NO) biology, these compensations can be interpreted either according to the “loss-without-penalty” alternative, or in the context of an excessive environmental oxygen supply at low cellular cost and oxygen requirement in the cold. Therefore, rather than reflecting oxygen limitation, several traits may indicate structural overcompensation of oxygen supply reductions at cell/tissue levels. At the multilevel cardio-circulatory adjustments, NO is revealing itself as a major integrator, compensating disaptation with functional phenotypic plasticity, as illustrated by the heart paradigm. Beside NOS-dependent NO generation, recent knowledge concerning Hb/Mb interplay with NO and nitrite has revealed unexpected functions in addition to the classical respiratory role of these proteins. In fact, nitrite, a major biologic reservoir of NO, generates it through deohyHb- and deoxyMb-dependent nitrite reduction, thereby regulating hypoxic vasodilation, cellular respiration and signalling. We suggest that both Hb and Mb are involved as nitrite reductases under hypoxic conditions in a number of cardiocirculatory processes. On the whole, this opens new horizons in environmental and evolutionary physiology.
Intensity modulated radiation therapy (IMRT) is increasingly employed in glioblastoma (GBM) treatment. The present work aimed to assess which clinical-dosimetric scenario could benefit the most from ...IMRT application, with respect to three-dimensional conformal radiation therapy (3D-CRT). The number of organs at risk (OARs) overlapping the planning target volume (PTV) was the parameter describing the clinical-dosimetric pattern. Based on the results, a dosimetric decision criterion to select the most appropriate treatment technique is provided. Seventeen previously irradiated patients were retrieved and re-planned with both 3D-CRT and IMRT. The prescribed dose was 60 Gy/30fx. The cases were divided into 4 groups (4 patients in each group). Each group represents the scenario where 0, 1, 2 or 3 OARs overlapped the target volume, respectively. Furthermore, in one case, 4 OARs overlapped the PTV. The techniques were compared also in terms of irradiated healthy brain tissue. The results were evaluated by paired t-test. IMRT always provided better target coverage (V95%) than 3D-CRT, regardless the clinical-dosimetric scenario: difference ranged from 0.82% (p = 0.4) for scenario 0 to 7.8% (p = 0.02) for scenario 3, passing through 2.54% (p = 0.18) and 5.93% (p = 0.08) for scenario 1 and 2, respectively. IMRT and 3D-CRT achieved comparable results in terms of dose homogeneity and conformity. Concerning the irradiation of serial-kind OARs, both techniques provided nearly identical results. A statistically significant dose reduction to the healthy brain in favor of IMRT was scored. IMRT seems a superior technique compared to 3D-CRT when there are multiple overlaps between OAR and PTV. In this scenario, IMRT allows for a better target coverage while maintaining equivalent OARs sparing and reducing healthy brain irradiation. The results from our patients dataset suggests that the overlap of three OARs can be used as a dosimetric criterion to select which patients should receive IMRT treatment.
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