[Methimazole Tablets-Induced Algospasm: Two Cases Report].

Here, we reported two cases with hyperthyroidism who complained of myalgia and muscle cramps during treatment with methimazole tablets (or Thyrozol, the brand name). One case experienced muscle cramps after taking Thyrozol for 6 months, and by this time the patient's thyroid function had returned to normal. In the other case, pain caused by muscular cramps began after the patient took Thyrozol for two weeks and the patient's thyroid function had not returned to normal yet at the time. In both cases, pain caused by muscle cramps appeared while the patients were taking Thyrozol. The myalgia persisted in spite of a reduction in the Thyrozol dose, but was significantly relieved with the discontinuation of Thyrozol. Myalgia and muscle cramps did not recur after the patients were switched to methimazole ointment. There was a strong temporal association between oral administration of Thyrozol and pain caused by muscle cramps, which may indicate that myalgia and muscle cramps are adverse reactions of Thyrozol. Looking into the relevant literature on the topic, we explored in this report the possible mechanisms of the onset of muscle cramps associated with Thyrozol, and compared the adverse reactions of two different formulations of methimazole, intending to provide more clinical experience for the treatment of hyperthyroidism and the management of rare adverse reactions related to antithyroid drugs.

Golgin Imh1 and GARP complex cooperate to restore the impaired SNARE recycling transport induced by ER stress.

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) induces the unfolded protein response (UPR), which acts through various mechanisms to reduce ER stress. While the UPR has been well studied for its effects on the ER, its impact on the Golgi is less understood. The Golgi complex receives transport vesicles from the endosome through two types of tethering factors: long coiled-coil golgin and the multisubunit Golgi-associated retrograde protein (GARP) complex. Here, we report that ER stress increases the phosphorylation of golgin Imh1 to maintain the GARP-mediated recycling of the SNAREs Snc1 and Tlg1. We also identify a specific function of the Golgi affected by ER stress and elucidate a homeostatic response to restore this function, which involves both an Ire1-dependent and a MAP kinase Slt2/ERK2-dependent mechanism. Furthermore, our findings advance a general understanding of how two different types of tethers act cooperatively to mediate a transport pathway.

Indole Compound NC009-1 Augments APOE and TRKA in Alzheimer's Disease Cell and Mouse Models for Neuroprotection and Cognitive Improvement.

Alzheimer's disease (AD), associated with abnormal accumulation of amyloid-ß (Aß), is the most common cause of dementia among older people. A few studies have identified substantial AD biomarkers in blood but their results were inconsistent. Here we screened gene expression alterations on Aß-GFP SH-SY5Y neuronal model for AD, and evaluated the findings on peripheral leukocytes from 78 patients with AD and 56 healthy controls. The therapeutic responses of identified biomarker candidates were further examined in Aß-GFP SH-SY5Y neuronal and APP/PS1/Tau triple transgenic (3×Tg-AD) mouse models. Downregulation of apolipoprotein E (APOE) and tropomyosin receptor kinase A (TRKA) were detected in Aß-GFP SH-SY5Y cells and validated by peripheral leukocytes from AD patients. Treatment with an in-house indole compound NC009-1 upregulated the expression of APOE and TRKA accompanied with improvement of neurite outgrowth in Aß-GFP SH-SY5Y cells. NC009-1 further rescued the downregulated APOE and TRKA and reduced Aß and tau levels in hippocampus and cortex, and ameliorated cognitive deficits in streptozocin-induced hyperglycemic 3×Tg-AD mice. These results suggest the role of APOE and TRKA as potential peripheral biomarkers in AD, and offer a new drug development target of AD treatment. Further studies of a large series of AD patients will be warranted to verify the findings and confirm the correlation between these markers and therapeutic efficacy.

Manipulation of radial-variant polarization for creating tunable bifocusing spots.

We propose and generate a new radial-variant vector field (RV-VF) with a distribution of states of polarization described by the square of the radius and exploit its focusing property. Theoretically, we present the analytical expressions for the three-dimensional electric field of the vector field focused by a thin lens under the nonparaxial and paraxial approximations based on the vectorial Rayleigh-Sommerfeld formulas. Numerical simulations indicate that this focused field exhibits bifocusing spots along the optical axis. The underlying mechanism for generating the bifocusing property is analyzed in detail. We give the analytical formula for the interval between two foci. Experimentally, we generate the RV-VFs with alterable topological charge and demonstrate that the interval between two foci is controllable by tuning the radial topological charge. This particular focal field has specific applications for biparticle trapping, manipulating, alignment, transportation, and accelerating along the optical axis.

Achievement of needle-like focus by engineering radial-variant vector fields.

We present and demonstrate a novel method for engineering the radial-variant polarization on the incident field to achieve a needle of transversally polarized field without any pupil filters. We generate a new kind of localized linearly-polarized vector fields with distributions of states of polarization (SoPs) describing by the radius to the power p and explore its tight focusing, nonparaxial focusing, and paraxial focusing properties. By tuning the power p, we obtain the needle-like focal field with hybrid SoPs and give the formula for describing the length of the needle. Experimentally, we systematically investigate both the intensity distributions and the polarization evolution of the optical needle by paraxial focusing the generated vector field. Such an optical needle, which enhances the light-matter interaction, has intriguing applications in optical microma-chining and nonlinear optics.

Amelioration of myocarditis by statin through inhibiting cross-talk between antigen presenting cells and lymphocytes in rats.

Statins, inhibitors of 3-hydroxy-3-methylglutary-coenzyme A (HMG-CoA) reductase, have been recognized as a new type of immunomodulator and reported to have anti-inflammatory effect. To investigate the effect of simvastatin, a lipophilic statin, on myocarditis, we explored whether simvastatin is able to inhibit experimental autoimmune myocarditis (EAM) and adoptive transfer of EAM in rats. We found that administration of simvastatin not only interfered with the development of EAM, but also inhibited the transfer. Antigen presenting cells (APCs) were proved to be important for the development of EAM. The ability of myocarditic splenocytes to transfer myocarditis was enhanced after co-culture with APCs. During co-culture of the myocarditic splenocytes and the APCs, simvastatin not only decreased percentages of CD28 expression in CD4-positive myocarditic splenocytes, and CD80 and CD86 expressions in APCs, but also inhibited the production of tumor necrosis factor (TNF)-partial differential in the CD4-positive myocarditic splenocytes and the APCs. These results indicate that simvastatin was able to ameliorate EAM through the inhibition of cross-talk between lymphocytes and APCs, suggesting beneficial role of simvastatin in the treatment of autoimmune myocarditis.