The importance of blood-count-derived inflammatory markers in predicting methotrexate success in patients with tubal ectopic pregnancy.

OBJECTIVE: To investigate the systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) in predicting a successful methotrexate response in tubal ectopic pregnancy (TEP). METHODS: Women treated for TEP at a tertiary hospital between 2017 and 2021 were retrospectively reviewed. A total of 502 (100%) eligible patients who received methotrexate were included and divided into two groups based on whether or not they were successfully treated with methotrexate alone. Inflammatory parameters derived from the patients' hemograms at hospital admission were compared. RESULTS: In total, 434 (86.4%) patients were successfully treated with methotrexate alone (Group 1), while 68 (13.6%) patients underwent surgery after methotrexate failure (Group 2). Median neutrophil count, NLR, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, SII, largest ectopic mass diameter, and ß-human chorionic gonadotropin (ß-hCG) were significantly lower, whereas median lymphocyte and platelet counts were significantly higher in Group 1. According to the receiver operating characteristic analysis performed for the discriminatory power of NLR, ß-hCG, and SII for methotrexate response, the area under the curve values were 0.742, 0.730, and 0.699, respectively. CONCLUSION: Low NLR and SII are associated with methotrexate success and could be used to refine decision making regarding ß-hCG for predicting successful response to methotrexate in patients with TEP.

A specific chiral HPLC method for lifitegrast and determination of enantiomeric impurity in drug substance, ophthalmic product and stressed samples.

Lifitegrast is a lymphocyte function-associated antigen-1 (LFA-1) antagonist used to treat the indications and symptoms associated with dry eye disease (DED), one of the most common ocular surface diseases. Lifitegrast has a chiral center, and the S-enantiomer (S-Lif) is responsible for the therapeutic effects, while the R-enantiomer (R-Lif) lacks efficacy in the treatment of DED. Lifitegrast ophthalmic solution containing 5% lifitegrast was approved by the United States Food and Drug Administration (FDA) in July 2016 for the treatment of DED in patients 17 years of age and older. The objective of this study was to develop a chiral HPLC method for the determination of the enantiomeric impurity of lifitegrast in the drug substance and in the ophthalmic product. In addition, we aimed to investigate the effect of stress and stability conditions on the enantiomeric purity of lifitegrast in both drug substance and ophthalmic solution. During the method development studies, four known lifitegrast impurities (Lif. Imp. A-D) and stressed lifitegrast samples were injected to ensure the specificity of the developed method. The enantiomers of lifitegrast are well separated with a resolution of higher than 4.0. They are also well separated from the peaks of the diluent, impurities, and the placebo used to prepare the ophthalmic solution without interference in 20 min. Chiral separation was achieved using a Chiralpak AD-H column (250 × 4.6 mm, 5.0 µm) at 40 °C with a mobile phase consisting of a mixture of n-hexane, 2-propanol, and formic acid (500:500:2, v/v/v) at a flow rate of 1.0 mL/min and a detection wavelength of 260 nm. Methanol was used as the diluent, and the drug substance solution was found to be stable for 48 h at 15 °C. The optimized chiral HPLC method for lifitegrast was validated according to ICH Q2, and the calibration curves showed excellent linearity for R-Lif (0.0369 - 1.816 µg/mL). This is the first stability-indicating, specific / selective, sensitive, linear, precise, accurate, and robust chiral HPLC method for the determination of R-Lif in S-Lif. The amount of enantiomeric impurity R-Lif in S-Lif increased under all stress and photostability test conditions without exceeding the acceptable impurity limit, with the most significant increase observed at elevated temperatures (105 °C) for both the drug substance in powder form and the ophthalmic drug solution.

The Course Patterns and Diagnostic Shifts of Patients With Schizoaffective Disorder: A Retrospective Cohort Study.

ABSTRACT: Since its introduction, schizoaffective disorder (SAD) has been one of the most controversial diagnoses in psychiatry, both clinically and nosologically. In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), SAD diagnostic criteria were changed, and instead of a cross-sectional diagnosis, a longitudinal approach covering the life course of the illness was adopted. In this study, the meaning of this conceptual shift in the diagnosis of SAD in clinical practice is investigated throughout the course of the illness for patients with SAD. Sixty-two inpatients diagnosed with SAD according to DSM-5 diagnostic criteria are included in this study. The course of the illness from its onset to the present is investigated retrospectively. The disease duration is 18.3 ± 9.1 years. The most common diagnoses in the first hospitalization are bipolar disorder (manic episodes) and psychotic disorder, not otherwise specified. Furthermore, the time that elapsed between the first psychiatric application of the patients and the diagnosis of SAD is 9.5 ± 7.3 years. Further, when the course of the illness is grouped according to the predominance of affective and psychotic disorders, recurrent affective disorders are observed most frequently (29.3%), followed by mixed-episode disorders and a shift from affective disorders to psychotic disorders (22.4%). It is found that SAD has a heterogeneous course, and affective disorder diagnoses are more dominant during the course of the illness. The clinical relevance of the longitudinal emphasis on the total duration of the illness in the DSM-5 is also demonstrated. The affective and psychotic dichotomy, based on Kraepelin, has failed to elucidate the course of the disease in clinical practice. Therefore, clinicians should meticulously evaluate the entire course of the illness for SAD and avoid conclusive judgments over a single episode.

Curcumin inhibits autocrine growth hormone-mediated invasion and metastasis by targeting NF-κB signaling and polyamine metabolism in breast cancer cells.

Curcumin is assumed to be a plant-derived therapeutic drug that triggers apoptotic cell death in vitro and in vivo by affecting different molecular targets such as NF-κB. Phase I/II trial of curcumin alone or with chemotherapeutic drugs has been accomplished in pancreatic, colon, prostate and breast cancer cases. Recently, autocrine growth hormone (GH) signaling-induced cell growth, metastasis and drug resistance have been demonstrated in breast cancer. In this study, our aim was to investigate the potential therapeutic effect of curcumin by evaluating the molecular machinery of curcumin-triggered apoptotic cell death via focusing on NF-κB signaling and polyamine (PA) metabolism in autocrine GH-expressing MCF-7, MDA-MB-453 and MDA-MB-231 breast cancer cells. For this purpose, a pcDNA3.1 (+) vector with a GH gene insert was transfected by a liposomal agent in all breast cancer cells and then selection was conducted in neomycin (G418) included media. Autocrine GH-induced curcumin resistance was overcome in a dose-dependent manner and curcumin inhibited cell proliferation, invasion-metastasis and phosphorylation of p65 (Ser536), and thereby partly prevented its DNA binding activity in breast cancer cells. Moreover, curcumin induced caspase-mediated apoptotic cell death by activating the PA catabolic enzyme expressions, which led to generation of toxic by-products such as H2O2 in MCF-7, MDA-MB-453 and MDA-MB-231 GH+ breast cancer cells. In addition, transient silencing of SSAT prevented curcumin-induced cell viability loss and apoptotic cell death in each breast cancer cells. In conclusion, curcumin could overcome the GH-mediated resistant phenotype via modulating cell survival, death-related signaling routes and activating PA catabolic pathway.

The effects of smoking on vascular endothelial growth factor and inflammation markers: A case-control study.

BACKGROUND AND AIMS: Chronic obstructive pulmonary disease (COPD) is a type of obstructive lung disease characterized by long-term poor airflow. Tobacco smoking is the most common cause of COPD. In this study, we aimed to assess the vascular endothelial growth factor (VEGF) and inflammation markers on smokers and non-smoking individuals. METHODS: Our study was a case-control study and 175 individuals who want to give up smoking constituted the case group. As a control group, 175 individuals who never smoked. RESULTS: The mean age of 350 participants was 35.83 ± 13.11 years. Educational status of the non-smokers was significantly higher than that of the smoking group (P < .001). When smoking and non-smoking groups were compared in terms of VEGF and interleukin-6 (IL-6), it was found that these values were statistically higher in smokers than non-smokers (P < .001). The levels of IL-10 were found to be higher in non-smokers than in smokers (P < .001). Although a moderate positive correlation was found between VEGF and IL-6 levels (r = .486, P < .001), there was a weak negative correlation between VEGF and IL-10 (r = -.210, P < .001). A weak negative correlation was found between IL-6 and IL-10 (r = -.185, P < .001). CONCLUSIONS: In our study, IL-6 inflammatory marker and VEGF levels were found to be high and IL-10 anti-inflammatory marker was discovered to be low in smokers. For this reason, raising awareness in the society about the harms of smoking and encouraging people to give it up have become more challenging to counteract the inflammatory effects of smoking in human body and to prevent many smoking-related diseases.