Mehanizam akutne neurotoksičnosti u Sprague-Dawley štakora izazvane trovanjem endosulfanom

The purpose of this study was to investigate the molecular mechanism underlying oxidative and inflammatory neuronal cell death induced by endosulfan, a pesticide belonging to the chemical family of organochlorines. The cortical and hippocampal tissues derived from Sprague-Dawley (SD) rats treated with endosulfan exhibited increased intracellular accumulation of reactive oxygen species and oxidative damages to cellular macromolecules such as depletion of glutathione, lipid peroxidation, and protein carbonylation. Conversely, the expression of antioxidant enzymes including γ-glutamylcysteine ligase (GCL), superoxide dismutase (SOD), and heme oxygenase-1 (HO-1) was markedly reduced in the brain tissues exposed to endosulfan. Moreover, during endosulfan-induced neuronal cell death, mRNA expression of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was elevated, which seemed to be mediated by the activation of nuclear factor-kappa B (NF-κB) by phosphorylation of p65 subunit. These results suggest a new molecular mechanism underlying the endosulfan-induced acute neurotoxicity via induction of oxidative stress and pro-inflammatory responses.Istražen je molekularni mehanizam koji dovodi do smrti neurona potaknute oksidativnim i upalnim procesima uzrokovanim organoklornim pesticidom endosulfanom. U tkivima korteksa i hipokampusa Sprague-Dawley (SD) štakora tretiranih endosulfanom uočena su oksidativna oštećenja staničnih makromolekula, poput smanjene razine glutationa, lipidne peroksidacije i karbonilacije proteina, te povećane unutarstanične akumulacije reaktivnih kisikovih spojeva. Isto tako, u moždanom tkivu nakon izlaganja endosulfanu značajno je smanjena ekspresija enzimskih antioksidansa, uključujući i γ-glutamilcistein ligazu (GCL), superoksidnu dismutazu (SOD) i hem oksigenazu-1 (HO-1). Tijekom endosulfanom izazvane smrti neurona povećala se i ekspresija mRNA pro-upalnih citokina poput čimbenika nekroze tumora-α (TNF-α) i interleukina-1β (IL-1β), što je čini se bilo posredovano aktivacijom nuklearnoga faktora kapa B (NF-κB) putem fosforilacije podjedinice p65. Navedeni rezultati upućuju na novi molekularni mehanizam koji stoji iza akutne neurotoksičnosti izazvane endosulfanom putem indukcije oksidativnoga stresa i pro-upalnih odgovora

Instantaneous ionization rate as a functional derivative

We describe an approach defining instantaneous ionization rate (IIR) as a functional derivative of the total ionization probability. The definition is based on physical quantities which are directly measurable, such as the total ionization probability and the waveform of the pulse. The definition is, therefore, unambiguous and does not suffer from gauge non-invariance. We compute IIR by solving numerically the time-dependent Schrodinger equation for the hydrogen atom in a strong laser field. We find that the IIR lags behind the electric field, but this lag is entirely due to the long tail effect of the Coulomb field. In agreement with the previous results using attoclock methodology, therefore, the IIR we define does not show measurable delay in strong field tunnel ionization

Risk factors for central and lateral lymph node metastasis in papillary thyroid carcinoma

Background Lymph node metastasis (LNM) is commonly observed in papillary thyroid carcinoma. This study aimed to investigate the risk factors for LNM in patients with papillary thyroid carcinoma. Methods The clinicopathological factors of 417 patients were investigated, and differences according to the presence or absence of LNM were evaluated. Results LNM was associated with age 10 mm, multiple and bilateral tumors, tumor involving the lower pole or entire lobe, lymphovascular invasion (LVI), perineural invasion (PNI), and extrathyroidal extension (ETE). Univariable and multivariable analyses showed that age 10 mm, LVI, and ETE were related to central LNM. Male sex, tumor size >10 mm, and LVI were correlated with lateral LNM (p10 mm, multifocality, PNI, ETE, and the absence of lymphocytic thyroiditis (p10 mm, LVI, and ETE were risk factors for central LNM, while male sex, tumor size >10 mm, and LVI were risk factors for lateral LNM. ENE was more commonly observed in lateral LNM, and tumor size >10 mm, multifocal tumors, PNI, ETE, and tumors unrelated to lymphocytic thyroiditis were risk factors for ENE

Immune-Checkpoint Inhibitors-Induced Type 1 Diabetes Mellitus: From Its Molecular Mechanisms to Clinical Practice

With the increasing use of immune-checkpoint inhibitors (ICIs), such as anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and anti-programmed cell death-1 (PD-1), for the treatment of malignancies, cases of ICI-induced type 1 diabetes mellitus (ICI-T1DM) have been reported globally. This review focuses on the features and pathogenesis of this disease. T1DM is an immune-related adverse event that occurs following the administration of anti-PD-1 or anti-programmed death ligand-1 (PD-L1) alone or in combination with anti-CTLA-4. More than half of the reported cases presented as abrupt-onset diabetic ketoacidosis. The primary mechanism of ICI-T1DM is T-cell stimulation, which results from the loss of interaction between PD-1 and PD-L1 in pancreatic islet. The similarities and differences between ICI-T1DM and classical T1DM may provide insights into this disease entity. ICI-T1DM is a rare but often life-threatening medical emergency that healthcare professionals and patients need to be aware of. Early detection of and screening for this disease is imperative. At present, the only known treatment for ICI-T1DM is insulin injection. Further research into the mechanisms and risk factors associated with ICI-T1DM development may contribute to a better understanding of this disease entity and the identification of possible preventive strategies

Photoionization in the presence of circularly polarized fundamental and odd-order harmonic fields

We present a study of the photoelectron spectra for the ionization process driven by counterrotating and corotating circularly polarized fundamental and odd-order harmonic fields. The main features of the spectra, such as symmetric lobed structures, are understood using simple arguments based on the strong field approximation (SFA) picture of ionization. A deviation from this picture is, most notably, the presence of the low-energy structures (LES) in the spectra. We show that the Rydberg states populated as a result of the combined absorption of the photons from the fundamental and harmonic fields are responsible for the origin of LES. © 2017 American Physical Society1111Nsciescopu