Computational investigations of click-derived 1,2,3-triazoles as keystone ligands for complexation with transition metals: a review

In recent years, metal complexes of organo 1,2,3-triazole click-derived ligands have attracted significant attention as catalysts in many chemical transformations and also as biological and pharmaceutical active agents. Regarding the important applications of these metal–organo 1,2,3-triazole-based complexes, in this review, we focused on the recently reported investigations of the structural, electronic, and spectroscopic aspects of the complexation process in transition metal complexes of 1,2,3-triazole-based click ligands. In line with this, the coordination properties of these triazole-based click ligands with transition metals were studied via several quantum chemistry calculations. Moreover, considering the complexation process, we have presented comparative discussions between the computational results and the available experimental data.

1,2,3-Triazole based ligands and their complexes with transition metals are used in pharmaceuticals and catalysis. Here we assess recent computational research on the structural, electronic and spectroscopic properties of these complexes.     

Origin and distribution of bone marrow-derived cells in the central nervous system in a mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is associated with increased numbers of microglia within the central nervous system (CNS). However, it is unknown whether the microgliosis results from proliferation of CNS resident microglia, or recruitment of bone marrow (BM)-derived microglial precursors. Here we assess the distribution and number of BM-derived cells in spinal cord using transplantation of green fluorescent protein (GFP)-labeled BM cells into myelo-ablated mice over-expressing human mutant superoxide dismutase 1 (mSOD), a murine model of ALS. Transplantation of GFP+ BM did not affect the rate of disease progression in mSOD mice. Mean numbers of microglia and GFP+ cells in spinal cords of control mice were not significantly different from those in asymptomatic mSOD mice and showed no change with animal age. The number of GFP+ cells and microglia (F4/80+ and CD11b+ cells) within the spinal cord of mSOD mice increased compared to age-matched controls at a time when mSOD mice exhibited disease symptoms, continuing up to disease end-stage. Although we observed an increase in the number of GFP+ cells in spinal cords of mSOD mice with disease symptoms, mean numbers of GFP+ F4/80+ cells comprised less than 20% of all F4/80+ cells and did not increase with disease progression. Furthermore, the relative rates of proliferation in CD45+GFP- and CD45+GFP+ cells were comparable. Thus, we demonstrate that the microgliosis present in spinal cord tissue of mSOD mice is primarily due to an expansion of resident microglia and not to the recruitment of microglial precursors from the circulation.     

Beyond prophylaxis: Extended risk of venous thromboembolism following primary debulking surgery for ovarian cancer

Objective

To determine the incidence and risk factors for venous thromboembolism (VTE) within six months after primary debulking surgery (PDS) for epithelial ovarian cancer (EOC).

Nutritional inadequacy in adults with muscular dystrophy

Patients with muscular dystrophy may be prone to nutrient deficiency due to mobility limitations or oropharyngeal weakness. Patients with myotonic muscular dystrophy (DM1) may be particularly prone to nutritional deficiencies from associated dysmotility of the entire gastrointestinal tract. We prospectively evaluated nutritional intake, body composition, and muscle strength in adult patients with DM1 (n = 29) and other muscular dystrophies (n = 22) on two occasions separated by approximately 6 months. Handgrip was significantly lower and knee extension higher for DM1 compared to other dystrophies, with no between-group differences in nutritional intakes. Many patients in both groups demonstrated inadequate nutrient intake of protein, energy, vitamins (water and fat soluble), and minerals (calcium and magnesium). Significant correlations were found between measures of strength and certain individual nutrients (e.g., copper and water-soluble vitamins). These data indicate that a substantial number of adults with muscular dystrophy do not meet current dietary intake recommendations. The potential clinical implications of these findings are discussed.     

Depleting tumor-specific Tregs at a single site eradicates disseminated tumors

Activation of TLR9 by direct injection of unmethylated CpG nucleotides into a tumor can induce a therapeutic immune response; however, Tregs eventually inhibit the antitumor immune response and thereby limit the power of cancer immunotherapies. In tumor-bearing mice, we found that Tregs within the tumor preferentially express the cell surface markers CTLA-4 and OX40. We show that intratumoral coinjection of anti–CTLA-4 and anti-OX40 together with CpG depleted tumor-infiltrating Tregs. This in situ immunomodulation, which was performed with low doses of antibodies in a single tumor, generated a systemic antitumor immune response that eradicated disseminated disease in mice. Further, this treatment modality was effective against established CNS lymphoma with leptomeningeal metastases, sites that are usually considered to be tumor cell sanctuaries in the context of conventional systemic therapy. These results demonstrate that antitumor immune effectors elicited by local immunomodulation can eradicate tumor cells at distant sites. We propose that, rather than using mAbs to target cancer cells systemically, mAbs could be used to target the tumor infiltrative immune cells locally, thereby eliciting a systemic immune response.     

High levels of CA125 (over 1,000 IU/ml) in patients with gynecologic disease and no malignant conditions: three cases and literature review

Objective To report the very high serum levels of CA125 in patients with benign gynecologic disease which manifests as pelvic mass. Methods Clinical data of three cases with high levels of CA125 over 1,000 IU/ml and benign gynecologic conditions were gathered. in Vali-Asr hospital. Results Three patients were scheduled for laparatomy as ovarian cancer and leiomyosarcoma. Histologic results after laparatomy showed uterine myoma in two patients and endometrioma in a third patient. Conclusion High levels of CA125 over 1,000 IU/ml, may be showed in other gynecologic conditions with no malignancy. So, other clinical and imaging data could be helpful for differential diagnosis of these patients.     

Warfarin-induced leukocytoclastic vasculitis

Skin reactions associated with oral coumarin-derived anticoagulants are an uncommon occurrence. Leukocytoclastic vasculitis (LV) is primarily a cutaneous small vessel vasculitis, though systemic involvement may be encountered. We report 4 patients with late-onset LV probably due to warfarin. All 4 patients presented with skin eruptions that developed after receiving warfarin for several years. The results of skin lesion biopsies were available in 3 patients, confirming LV Cutaneous lesions resolved in all patients after warfarin was discontinued. In 2 of the 4 patients, rechallenge with warfarin led to recurrence of the lesions. LV may be a late-onset adverse reaction associated with warfarin therapy.