Povećanje incidencije otrovanja biljnim i životinjskim toksinima tijekom proteklih godina ukazuje na važnost poznavanja otrovnih vrsta na području Republike Hrvatske. Od otrovnih biljnih vrsta u ...Republici Hrvatskoj raste velebilje, kranjski bijeli bun, duhan, bunovina, crna bunika, bijeli kužnjak, crni kukurijek i jesenski mrazovac. Većina otrovnih biljaka pripada porodici pomoćnica (Solanaceae). To su biljke bogate tropanskim alkaloidima koji djeluju kao antikolinergične tvari. Imaju antagonističko djelovanje na muskarinske acetilkolinske receptore. S obzirom na široku rasprostranjenost navedenih receptora u ljudskom organizmu, pri intoksikaciji tim biljkama dolazi do poremećaja rada srca, inhibicije ili stimulacije lučenja pojedinih žlijezda, kao i poremećaja intestinalnog motiliteta. Jedan je od najpoznatijih učinaka pojava delirija i halucinacija koji nastaju zbog inhibicije muskarinskih acetilkolinskih receptora u mozgu. Opisane su i otrovne gljive, iako one pripadaju zasebnome carstvu. U našem području najvažnije su zelena pupavka i muhara. Ove gljive pripadaju rodu Amanita u kojima nalazimo dvije grupe toksina, falotoksine i amatoksine koji inhibiraju RNA polimerazu II i time onemogućuju sintezu vitalno važnih bjelančevina. Od životinjskih toksina opisani su toksini zmija, paukova i riba. Većina zmija otrovnica u Republici Hrvatskoj pripada porodici Viperidae. Naše su najpoznatije otrovnice poskok i riđovka. Njihov otrov sadrži hijaluronidaze, fosfolipazu A2 i metaloproteinaze. Od paukova opisani su crna udovica i smeđi primorski riječni pauk. Otrov pauka smjesa je monoamina, koji djeluju proalgetski, peptida s ekscitatornim učincima koji izazivaju nociceptivni odgovor. Završni dio osvrće se na ribe otrovnice, škrpinu i morskog pauka.
If immunized with an antigen of interest, transgenic mice with large portions of unrearranged human immunoglobulin loci can produce fully human antigen-specific antibodies; several such antibodies ...are in clinical use. However, technical limitations inherent to conventional transgenic technology and sequence divergence between the human and mouse immunoglobulin constant regions limit the utility of these mice. Here, using repetitive cycles of genome engineering in embryonic stem cells, we have inserted the entire human immunoglobulin variable-gene repertoire (2.7 Mb) into the mouse genome, leaving the mouse constant regions intact. These transgenic mice are viable and fertile, with an immune system resembling that of wild-type mice. Antigen immunization results in production of high-affinity antibodies with long human-like complementarity-determining region 3 (CDR3H), broad epitope coverage and strong signatures of somatic hypermutation. These mice provide a robust system for the discovery of therapeutic human monoclonal antibodies; as a surrogate readout of the human antibody response, they may also aid vaccine design efforts.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Obesity is associated with metabolic dysregulation characterized by insulin resistance and glucose intolerance. Nuclear factor E2-related factor (Nrf2) is a critical regulator of the stress response ...and Nrf2-deficient mice (Nrf2−/−) are protected against high fat diet (HFD)-induced metabolic derangement. We searched for factors that could underline this favorable phenotype and found that Nrf2−/− mice exhibit higher circulating levels of sirtuin 1 (Sirt1), a key player in cellular homeostasis and energy metabolism, compared to wild-type mice. Increased Sirt1 levels in Nrf2−/− mice were found not only in animals under standard diet but also following HFD. Interestingly, we report here that the visceral adipose tissue (eWAT) is the sole source of increased Sirt1 protein in plasma. eWAT and other fat depots displayed enhanced adipocytes lipolysis, increased fatty acid oxidation and glycolysis, suggesting autocrine and endocrine actions of Sirt1 in this model. We further demonstrate that removal of eWAT completely abolishes the increase in circulating Sirt1 and that this procedure suppresses the beneficial effect of Nrf2 deficiency on glucose tolerance, but not insulin sensitivity, following a HFD regime. Thus, in contrast to many other stressful conditions where Nrf2 deficiency exacerbates damage, our study indicates that up-regulation of Sirt1 levels specifically in the visceral adipose tissue of Nrf2−/− mice is a key adaptive mechanism that mitigates glucose intolerance induced by nutritional stress.
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•Nrf2−/− mice are protected against weight gain and metabolic dysfunction under high fat diet (HFD).•Nrf2−/− mice display increased production of sirtuin 1 exclusively in visceral white adipose tissue (eWAT).•Removal of eWAT prior to HFD abolishes the increase in sirtuin 1 and impairs glucose tolerance.•A strong link exists between Nrf2 deficiency, SIRT1 in eWAT and regulation of glucose homeostasis.
Biotherapeutics, molecules produced from biological systems, require rigorous purification steps to remove impurities including host cell proteins (HCPs). Regulatory guidelines require manufacturers ...to monitor process‐related impurities along the purification workflow. Mass spectrometry (MS) has recently been considered as a complementary method to the well‐established ELISA for HCPs quantification, since it has the advantage of unambiguously identifying individual HCP. In this study, we developed an innovative standard dedicated to MS‐based HCP profiling analysis in order to monitor the consistency of viral vaccine intermediate purification samples. This standard, termed the HCP‐PROFILER standard, is composed of a water‐soluble bead (READYBEADS technology) which, after being added into the sample, releases unlabeled peptides in controlled amounts. The standard meets three desired criteria: (1) it is composed of multiple peptides, at different concentration levels, allowing construction of a calibration curve covering the dynamic range of HCPs present in the target sample, ensuring quantification accuracy; (2) it demonstrates high batch‐to‐batch reproducibility, ensuring quantification robustness and consistency over time; and (3) it is easy to use and avoids user‐induced analytical biases. In this study, we present the use of the HCP‐PROFILER standard for vaccine batches comparison and downstream process performance studies.
Obesity is characterized by accumulation of adipose tissue and is one the most important risk factors in the development of insulin resistance. Carbon monoxide-releasing (CO-releasing) molecules ...(CO-RMs) have been reported to improve the metabolic profile of obese mice, but the underlying mechanism remains poorly defined. Here, we show that oral administration of CORM-401 to obese mice fed a high-fat diet (HFD) resulted in a significant reduction in body weight gain, accompanied by a marked improvement in glucose homeostasis. We further unmasked an action we believe to be novel, by which CO accumulates in visceral adipose tissue and uncouples mitochondrial respiration in adipocytes, ultimately leading to a concomitant switch toward glycolysis. This was accompanied by enhanced systemic and adipose tissue insulin sensitivity, as indicated by a lower blood glucose and increased Akt phosphorylation. Our findings indicate that the transient uncoupling activity of CO elicited by repetitive administration of CORM-401 is associated with lower weight gain and increased insulin sensitivity during HFD. Thus, prototypic compounds that release CO could be investigated for developing promising insulin-sensitizing agents.
Obesity is associated with metabolic dysregulation characterized by insulin resistance and glucose intolerance. Nuclear factor E2-related factor (Nrf2) is a critical regulator of the stress response ...and Nrf2-deficient mice (Nrf2-/-) are protected against high fat diet (HFD)-induced metabolic derangement. We searched for factors that could underline this favorable phenotype and found that Nrf2-/- mice exhibit higher circulating levels of sirtuin 1 (Sirt1), a key player in cellular homeostasis and energy metabolism, compared to wild-type mice. Increased Sirt1 levels in Nrf2-/- mice were found not only in animals under standard diet but also following HFD. Interestingly, we report here that the visceral adipose tissue (eWAT) is the sole source of increased Sirt1 protein in plasma. eWAT and other fat depots displayed enhanced adipocytes lipolysis, increased fatty acid oxidation and glycolysis, suggesting autocrine and endocrine actions of Sirt1 in this model. We further demonstrate that removal of eWAT completely abolishes the increase in circulating Sirt1 and that this procedure suppresses the beneficial effect of Nrf2 deficiency on glucose tolerance, but not insulin sensitivity, following a HFD regime. Thus, in contrast to many other stressful conditions where Nrf2 deficiency exacerbates damage, our study indicates that up-regulation of Sirt1 levels specifically in the visceral adipose tissue of Nrf2-/- mice is a key adaptive mechanism that mitigates glucose intolerance induced by nutritional stress.
Trans-catheter aortic valve implantation (TAVI) is an increasingly adopted technique which provides a minimal invasive solution for patients who suffer from severe aortic stenosis. Some complications ...of the procedure could be annular rupture or paravalvular leakage, both related with adverse outcome. In TAVI with balloon expandable devices, a mismatch between those two factors leads to a conflict situation, where improving one worsens the other. The presented research proposes a methodology that uses numerical simulation to obtain certain TAVI outcomes related with aortic regurgitation due to paravalvular leakage, such as perivalvular area, aortic eccentricity or annular pressure. The application of the methodology for two patients shows the possibility of predicting those quantities. The highest stress values are distributed along the contact area. Results also show that a great deformation on the aortic annulus does not necessarily imply a higher stress; pressure can either be converted into root reshape or into root stretching. Validation of the results was done using scientific publications, clinical guidelines and clinical reports. Numerical simulation provides a suitable tool that could possibly contribute to optimize the planification procedure adjusting the mismatch between size and pressure.
Exposure to hexavalent chromium (Cr
6+) causes mutagenic, carcinogenic, and toxic effects, some of which have been associated with its oxidative capacity. In the kidney, Cr
6+ has been claimed to ...provoke necrosis of the proximal tubular cells. Our aim was to assess the functional involvement of the different segments that form the nephron in a model of acute renal failure caused by potassium dichromate and the participation of oxidative damage in this process. We also studied the possible protective effect of α-tocopherol (α-TOC) against renal damage. Wistar female rats 200
g body weight (bw) received potassium dichromate (15
mg/kg, sc, single dose). Lipid peroxidation and renal function were evaluated on days 0, 1, 2, 3, 7, 10, and 14. A second group received α-TOC (125
mg/kg, by gavage) 5 days before and during dichromate exposure (same dose as for the first group), and was monitored at 0, 2, and 7 days of exposure. Creatinine clearance, glucose and sodium fractional excretions,
p-aminohippurate uptake, free-water and osmolal clearances were also measured. Thiobarbituric acid-reactive substances were quantified in renal cortex. The results revealed altered proximal tubule function, decreased glomerular filtration, and distal segment dysfunction, accompanied by oxidative damage 48
h after exposure to dichromate. In the α-TOC-treated group proximal reabsorptive and secretory functions were preserved, suggesting that oxidative damage is a participating mechanism in dichromate toxicity on these functions. In contrast α-TOC did not prevent glomerular or distal dysfunction, indicating selectivity of the protection afforded by this compound on the toxicity of dichromate, at the several components of the nephron.
Panamá, país de tránsito para productores y consumidores de drogas, generando economía emergente, cultura de violencia y maltrato en la familia y comunidad, siendo niños y adolescentes vulnerables al ...uso y abuso de drogas por exposición prolongada al maltrato. Se determina independencia o relación entre uso y abuso de droga con el maltrato durante la niñez y la adolescencia en estudiantes en una universidad en la ciudad de Panamá. Se aplicó el método cuantitativo, diseño transeccional, correlacional, muestreo estratificado, muestra de 377 estudiantes de 12 facultades por afijación proporcional. Instrumento aplicado: "Cuestionario Uso de Drogas y Experiencias Adversas de la niñez". La prueba chi-cuadrado, test de independencia, comprobó no independencia entre uso y abuso de drogas posterior al maltrato como abuso sexual, con p-valor asociado 0,021, al 95% nivel de confianza, con significancia de p< de 0,05; determinantes para consumo posterior: madre maltratada, separación o divorcio de padres, pares consumidores.
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