Influence of state-of-the-art laboratory techniques on the phenotyping of women with polycystic ovary syndrome in the clinical setting.

PURPOSE: Evidence-based guidelines for the management of polycystic ovary syndrome (PCOS) recommend clinical laboratories use liquid chromatography-tandem mass spectrometry (LC-MS/MS) for diagnosing biochemical hyperandrogenism. However, automated immunoassays are still mostly used in routine laboratories worldwide. Another hurdle for PCOS phenotyping in the clinical setting is ultrasound assessment of polycystic ovarian morphology. We address the impact of using state-of-the-art (LC-MS/MS) and of an anti-müllerian hormone (AMH) assay on the diagnosis of PCOS in routine practice. METHODS: In a cross-sectional study, we included 359 premenopausal women consecutively evaluated because of symptoms of functional androgen excess or hyperandrogenemia, and finally diagnosed with PCOS. Patients were submitted to routine phenotyping based on serum androgen measurements by immunoassays and an ovarian ultrasound when necessary. Samples of all patients were also assayed by LC-MS/MS for hyperandrogenemia and for circulating AMH. RESULTS: The observed agreement between immunoassays and LC-MS/MS in identifying hyperandrogenemia was poor [78.0%; k(95%CI): 0.366 (0.283;0.449)]. The observed agreement between ultrasound and increased AMH was 27.3% [(95%CI): 0.060 (0.005; 0.115)]. Using LC-MS/MS changed PCOS phenotypes in 60(15.8%) patients. Fifty-two (18.3%) individuals with hyperandrogenemia by routine immunoassays no longer presented with androgen excess by LC-MS/MS. Overall diagnostic agreement between routine assessment using immunoassays and ultrasound and that derived from LC-MS/MS and the addition of AMH to US was moderate [weighted κ (linear weights): 0.512 (0.416;0.608)]. CONCLUSIONS: Immunoassays used in routine practice are unacceptably inaccurate for phenotyping women with PCOS. Our data cast some doubts upon the interchangeability of serum AMH and ultrasound examination for the diagnosis of PCOS.

Comparison of demographic, clinic and radiological features of patients with axial spondyloarthritis accompanying familial Mediterranean fever to patients with each condition alone.

OBJECTIVE: To compare the demographic, clinical, and radiological features of patients with axial spondyloarthritis (axSpA) accompanying familial Mediterranean fever (FMF) to patients with each condition alone. METHOD: Hacettepe University Hospital database was screened regarding ICD-10 codes for FMF (E85.0) and axSpA (M45). The diagnosis of FMF was confirmed by Tel-Hashomer criteria, and axSpA by the presence of sacroiliitis according to the modified New York criteria or active sacroiliitis on magnetic resonance imaging. As control groups, 136 gender-matched, consequent FMF patients without axSpA and 102 consequent axSpA patients without FMF previously treated with any biological agents were included in the analysis. RESULTS: In patients with FMF + axSpA compared to the axSpA group, age at axSpA symptom onset and age at diagnosis were lower [median with interquartile range (IQR): 21 (17-30) vs 27 (21-37), p < 0.001; 23 (21-38) vs 32 (24-43) years, p = 0.001], moderate to severe hip disease and total hip replacement were more prevalent (23.4% vs 4.7%, p < 0.001; 11.2% vs 2.8%, p = 0.016). In patients with FMF + axSpA compared to the FMF group, age at FMF symptom onset and age at diagnosis were higher [13 (6-30) vs 11 (5-18), p = 0.057; 23 (13-33) vs 18 (10-31) years, p = 0.033] and amyloidosis was more prevalent (6.6% vs 2.2%, p = 0.076). Although the M694V variant (in one or two alleles) was more prevalent in the FMF + axSpA group, the difference was not statistically significant. CONCLUSION: In patients with FMF + axSpA, the age of onset of axSpA was significantly earlier, moderate to severe hip involvement and amyloidosis were more common than in patients with each condition alone.

Embryo blastulation and quality between days 5 and 6 of extended embryo culture.

PURPOSE: This study aims to know what proportion of culture day 5 pre-blastocyst-stage embryos develop into blastocysts by culture day 6 and what patient and cycle characteristics are associated with delayed blastocyst formation. METHODS: A retrospective observational cohort analysis was performed including a total of 9886 embryos from 1008 IVF cycles in 835 patients, who underwent treatment between January 1, 2016, and December 31, 2018. Autologous fresh in vitro fertilization (IVF) cycles at a single academic center were included in the analysis. Embryos were group-cultured using single-step culture media. Blastulation was defined as the presence of a new blastocyst. Usable blastulation was defined as the presence of a new good or excellent quality, expanded, hatching, or hatched blastocysts. RESULTS: The mean blastulation rate between days 5 and 6 of extended embryo culture was 30.9%. The mean percentage of embryos developing into usable blastocyst-stage embryos was 19.8%. The factors associated with blastulation on day 6 included the total number of embryos and the number of pre-blastocysts on day 5, as well as the use of ICSI. Age, the number of total embryos, those remained in culture and pre-blastocysts, as well as the blastulation rate on day 5 were associated with usable blastulation. CONCLUSION: It is important to know the usable blastocyst development rate between culture days 5 and 6 in order to adequately counsel patients debating whether to proceed with fresh ET on day 5 or forego ET with the expectation that embryos will be biopsied for PGT and/or cryopreserved on culture day 6. Our findings provide evidence to help guide patients in this difficult decision.

Analysis of the effectiveness of the prophylaxis of vestibular migraine depending on the diagnostic category and the prescribed drug.

INTRODUCTION: Vestibular migraine (VM) consists of recurrent episodes of vestibular symptoms that are accompanied by migraine in at least 50% of the episodes. The criteria of the Bárány Society include two diagnostic categories: "actual" vestibular migraine and probable vestibular migraine. There is a wide range of drugs that can be prescribed for the prophylactic treatment of VM, but recommendations for the selection of the most appropriate drug are currently lacking. OBJECTIVE: To measure the extent to which the prophylactic treatment of VM reduces vestibular symptoms, headache and the number of crises depending on the diagnostic category of the Bárány Society and the drug used for prophylaxis. MATERIAL AND METHODS: This is a multicenter prospective study. Patients with VM who presented to any of the participating centers and who subsequently met the VM criteria were prescribed one of the following types of prophylaxis: acetazolamide, amitriptyline, flunarizine, propranolol or topiramate. Patients were called back for a follow-up visit 5 weeks later. This allowed the intensity of vestibular symptoms, headache and the number of crises before and during treatment to be compared. RESULTS: 31 Patients met the inclusion criteria. During the treatment, all the measured variables decreased significantly. In a visual analogue scale, the intensity of vestibular symptoms decreased by 45.8 points, the intensity of headache decreased by 47.8 points and patients suffered from 15.6 less monthly crises compared to the period before the treatment. No significant between-group differences were found when patients were divided based on their diagnostic category or the choice of prophylaxis prescribed to them. CONCLUSION: The treatment of VM produces a reduction of symptoms and crises with no significant differences based on patients' diagnostic categories or the choice of prophylaxis prescribed to them.

Healing criteria: How should an episode of benign paroxistic positional vertigo of posterior semicircular canal's resolution be defined? Prospective observational study.

OBJECTIVES: To compare the outcome of the Epley maneuver (EM) in benign paroxysmal positional vertigo of the posterior canal (CSP-BPPV) depending on the definition used for recovery. DESIGN: Multicenter observational prospective study. SETTING: Otoneurology Units of 5 tertiary reference hospitals. PARTICIPANTS: All patients presenting with unilateral CSP-BPPV assisted for 1-year period. EXCLUSION CRITERIA: Spontaneous nystagmus, positive McClure-Pagnini maneuver, positive bilateral Dix-Hallpike maneuver (DHM), positive DHM for vertigo but negative for nystagmus and atypical nystagmus. MAIN OUTCOME MEASURES: Response to EM was measured after 7 days in 3 different outcomes: disappearance of nystagmus during the DHM in the follow-up visit, disappearance of vertigo during the DHM and general status (GS) during daily life activities. RESULTS: 264 patients were recruited (68 male/166 female, mean age 62 years). After the EM, nystagmus disappeared in 67% of them, vertigo in 54% and 36% were asymptomatic in their daily life. These outcomes were strongly correlated, but they were not concordant in a clinically significant group of cases; only the 26% of patients met all of them. The healing process follows the next sequence: negativization of positional nystagmus, then disappearance of positional vertigo and, finally, the improvement of GS during daily life activities. CONCLUSION: Nowadays, healing criteria for the resolution of an PSC-BPPV episode have not been specifically defined yet. Provided that other otoneurological disorders have been ruled out, the next resolution criterion is proposed: absence of nystagmus and specifically during control DHM and disappearance of symptoms during daily life activities.

Long-term clinical impact of permanent cardiac pacing after transcatheter aortic valve implantation with the CoreValve prosthesis: a single center experience.

Aims: To determine the impact of permanent cardiac pacing after transcatheter aortic valve implantation (TAVI) with the CoreValveTM prosthesis in terms of all-cause mortality and morbidity [rehospitalizations for heart failure (HF) or stroke] at the long-term follow-up. Methods and results: The prospective analysis comprised 259 patients (138 women, 53.3%, age 78 ± 6 years) treated by a CoreValveTM prosthesis from April 2008 to December 2015. Forty-two patients were excluded for analysis: 9 with pre-existing permanent pacemaker (PPM) implantation, 19 who required a PPM during the follow-up and 14 patients because of hospital mortality during or after the CoreValveTM prosthesis implantation procedure. The remaining 217 patients were divided in two groups: Group-1 included those patients who required a PPM immediately after TAVI, and Group-2 included those patients who did not require permanent cardiac pacing at the long-term follow-up. Patients received follow-up at 1-month, 6-months, 12-months, and yearly thereafter. A total of 39 patients required a PPM immediately after TAVI (15.0%), but 178 patients (68.7%) did not. The mean follow-up was 37 ± 27 months (range 3-99 months) in both groups. There was no difference between the two groups in terms of all-cause mortality (52.6% vs. 56.8%, P = 0.125; HR 1.22 [0.87-1.77, 95% CI]), or stroke (13.3% vs. 15.1% P = 0.842; HR 1.12 [0.37-3.32, 95% CI]). However, patients who underwent PPM implantation developed an increase in readmissions for HF (21.1% vs. 31.9%, P = 0.015; HR 1.82 [1.23-3.92, 95% CI]). Conclusion: Patients requiring a PPM after TAVI did not have an increase in mortality, or an increase in the likelihood of developing a stroke at a long-term follow-up. However, this subgroup of patients showed an increase in rehospitalization due to HF at medium- and long-term follow-up.

Identification of dizzy patients who will develop an acute cerebrovascular syndrome: a descriptive study among emergency department patients.

PURPOSE: To calculate the incidence of subsequent acute cerebrovascular syndrome in emergency department patients with vertigo or dizziness symptoms and to determine predictors of subsequent acute cerebrovascular syndrome in these patients. METHODS: Descriptive and retrospective hospital based-population study among emergency department patients with vertigo or dizziness symptoms in 1 year. One year follow-up since the medical visit was performed. Chi-square and Fisher tests were used for qualitative variables; Mann-Whitney U test for quantitative variables. A multivariate model was created. RESULTS: 1243 dizzy patients who visited emergency department during 2015 were identified, finally 928 were included. 12 acute cerebrovascular syndromes were identified; 8 strokes and 4 transient ischemic attacks. Percentages over the sample size: 1.29% for acute cerebrovascular syndromes, 0.43% for transient ischemic attack and 0.86% for stroke. Odds ratio values to develop an event over the general population were 7.24 for acute cerebrovascular syndrome, 95% CI (3.98-13.12); 14.9 for transient ischemic attack, 95% CI (4.8-40.9) and 5.86 for stroke, 95% CI (2.72-12.0). Atrial fibrillation and diabetes mellitus were identified as significant risk factors to develop an acute cerebrovascular syndrome. CONCLUSION: Emergency department patients with symptoms of vertigo or dizziness had sevenfold higher risk of acute cerebrovascular syndromes than the general population. Atrial fibrillation and diabetes mellitus are risk factors associated with high risk of acute cerebrovascular syndromes in these patients.

Gabapentin pretreatment for propofol and rocuronium injection pain: A randomized, double-blind, placebo-controlled study.

AIM: This prospectively-planned, randomized, double-blind and placebo-controlled study aims to evaluate the effect of 1200 mg gabapentin premedication on the incidence and severity of propofol and rocuronium injection pain. METHOD: One hundred patients, between 18-60 years of age and ASA I-II for elective surgery planned under general anaesthetic, were randomized and divided into two groups. Two hours before the operation, the patients were given either a placebo tablet (Group P, n = 50) or 1200 mg gabapentin tablet (Group G, n = 50). On the back of the non-dominant hand, a vein was opened using a 20 G cannula , 0.9% NaCl was begun and preoxygenation was provided. For anaesthesia induction, 1% propofol at 800 ml/hr infusion rate was administered for 20 s. Propofol injection pain was evaluated up to the 20th second and recorded using a scale between 0 and 3 developed by McCrirrick and HunteR The remaining propofol dose (2.5 mg/kg), 5 ml saline and 0.6 mg/kg rocuronium were injected in that order over 10 seconds and rocuronium injection pain response was evaluated with a four point scale. RESULTS: Pain after propofol infusion average score (degree ≥ 1) (Group G = 0.5; Group P = 1.0) and incidence (Group G = 46%; Group P = 68%); and average withdrawal movements response score linked to rocuronium injection pain (≥ 1 response) (Group G = 0.3; Group P = 1.2) and incidence (Group G = 20%; Group P = 80%) were detected to be significantly lower in the gabapentin group compared to the placebo group (p < 0.001). CONCLUSION: Premedication with 1200 mg gabapentin 2 hours before propofol and rocuronium injection reduced the incidence and severity of injection pain.

Analysis of risk factors influencing the outcome of the Epley maneuver.

Benign paroxysmal positional vertigo (BPPV) is the most frequent type of vertigo. The treatment of canalithiasis of the posterior semicircular canal consists in performing a particle-repositioning maneuver, such as the Epley maneuver (EM). However, the EM is not effective in all cases. The objective of this study is to identify risk factors, which predict the EM failure, among the clinical variables recorded in anamnesis and patient examination. This is an observational prospective multicentric study. All patients presenting with BPPV were recruited and applied the EM and appointed for a follow-up visit 7 days later. The following variables were recorded: sex, age, arterial hypertension, diabetes, hyperlipidemia, smoking habit, alcohol consumption, migraine, osteoporosis, diseases of the inner ear, previous ipsilateral BPPV, previous traumatic brain injury, previous sudden head deceleration, time of evolution, sulpiride or betahistine treatment, experienced symptoms, outcome of the Halmagyi maneuver, laterality, cephalic hyperextension of the neck, intensity of nystagmus, intensity of vertigo, duration of nystagmus, occurrence of orthotropic nystagmus, symptoms immediately after the EM, postural restrictions, and symptoms 7 days after the EM. Significant differences in the rate of loss of nystagmus were found for six variables: hyperlipidemia, previous ipsilateral BPPV, intensity of nystagmus, duration of nystagmus, post-maneuver sweating, and subjective status. The most useful significant variables in the clinical practice to predict the success of the EM are previous BPPV and intensity of nystagmus. In the other significant variables, no physiopathological hypothesis can be formulated or differences between groups are too small.

First description of the neuro-anatomy of a larval coral reef fish Amphiprion ocellaris.

The present study described the neuro-anatomy of a larval coral reef fish Amphiprion ocellaris and hypothesized that morphological changes during the transition from the oceanic environment to a reef environment (i.e. recruitment) have the potential to be driven by changes to environmental conditions and associated changes to cognitive requirements. Quantitative comparisons were made of the relative development of three specific brain areas (telencephalon, mesencephalon and cerebellum) between 6 days post-hatch (dph) larvae (oceanic phase) and 11 dph (at reef recruitment). The results showed that 6 dph larvae had at least two larger structures (telencephalon and mesencephalon) than 11 dph larvae, while the size of cerebellum remained identical. These results suggest that the structure and organization of the brain may reflect the cognitive demands at every stage of development. This study initiates analysis of the relationship between behavioural ecology and neuroscience in coral reef fishes.

Human decidual stromal cells secrete soluble pro-apoptotic factors during decidualization in a cAMP-dependent manner.

STUDY QUESTION: Is there a relationship between decidualization and apoptosis of decidual stromal cells (DSC)? SUMMARY ANSWER: Decidualization triggers the secretion of soluble factors that induce apoptosis in DSC. WHAT IS KNOWN ALREADY: The differentiation and apoptosis of DSC during decidualization of the receptive decidua are crucial processes for the controlled invasion of trophoblasts in normal pregnancy. Most DSC regress in a time-dependent manner, and their removal is important to provide space for the embryo to grow. However, the mechanism that controls DSC death is poorly understood. STUDY DESIGN, SIZE, DURATION: The apoptotic response of DSC was analyzed after exposure to different exogenous agents and during decidualization. The apoptotic potential of decidualized DSC supernatants and prolactin (PRL) was also evaluated. PARTICIPANTS/MATERIALS, SETTING, METHODS: DSC lines were established from samples of decidua from first trimester pregnancies. Apoptosis was assayed by flow cytometry. PRL production, as a marker of decidualization, was determined by enzyme-linked immunosorbent assay. MAIN RESULTS AND THE ROLE OF CHANCE: DSCs were resistant to a variety of apoptosis-inducing substances. Nevertheless, DSC underwent apoptosis during decidualization in culture, with cAMP being essential for both apoptosis and differentiation. In addition, culture supernatants from decidualized DSC induced apoptosis in undifferentiated DSC, although paradoxically these supernatants decreased the spontaneous apoptosis of decidual lymphocytes. Exogenously added PRL did not induce apoptosis in DSC and an antibody that neutralized the PRL receptor did not decrease the apoptosis induced by supernatants. LIMITATIONS, REASONS FOR CAUTIONS: Further studies are needed to examine the involvement of other soluble factors secreted by decidualized DSC in the induction of apoptosis. WIDER IMPLICATIONS OF THE FINDINGS: The present results indicate that apoptosis of DSC occurs in parallel to differentiation, in response to decidualization signals, with soluble factors secreted by decidualized DSC being responsible for triggering cell death. These studies are relevant in the understanding of how the regression of decidua, a crucial process for successful pregnancy, takes place. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Consejería de Economía, Innovación y Ciencia, Junta de Andalucía (Grant CTS-6183, Proyectos de Investigación de Excelencia 2010 to C.R.-R.) and the Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Spain (Grants PS09/00339 and PI12/01085 to E.G.O.). E.L.-D. was supported by fellowships from the Ministerio de Educación y Ciencia, Spain and the University of Granada. The authors have no conflict of interest.

Determination of the optimal position of the lower extremity for femoral nerve block with ultrasonographic measurements: a prospective volunteer-based study.

OBJECTIVE: The aim of the study was to determine the optimal position for femoral nerve block (FNB) under ultrasound guidance. PATIENTS AND METHODS: We included fifty volunteers between 18-65 years of age in this study. The distances from the skin to the landmarks, which were taken as a reference for the ultrasound-guided FNB (apex point of the femoral artery = F12, lateral point = F9, and lower point = F6), were measured and compared in 3 different positions given to the lower extremity (neutral position: P1, 45° abduction: P2, and flexed knee: P3). The ease of application and the quality of the ultrasound images were evaluated at each measurement by assigning a subjective observer score and comparing them in three positions. RESULTS: All three measurement points were found to be closest to the skin at position P3. However, the distances from F9 (p = 0.023) and F6 (p = 0.006) to the skin were significant. A significant difference was found between P1 and P3 in terms of the distance from F9 (p = 0.027) and F6 to the skin (p = 0.007). P3 was determined to be the position with the highest score for clarity of the ultrasonography images and ease of detection of the measurement points (p < 0.001). As the scores of ease of access to the femoral nerve (FN) and image clarity increased, the distance from the measurement point to the skin surface decreased, which was statistically significant. CONCLUSIONS: The ideal position for ultrasound-guided FNB is the P3 position. As an alternative for patients with limited mobility, the P2 position can be used.

Allergy and acute leukaemia in children with Down syndrome: a population study. Report from the Mexican inter-institutional group for the identification of the causes of childhood leukaemia.

BACKGROUND: Allergies have been described as protective factors against the development of childhood acute leukaemia (AL). Our objective was to investigate the associations between allergy history and the development of AL and acute lymphoblastic leukaemia (ALL) in children with Down syndrome (DS). METHODS: A case-control study was performed in Mexico City. The cases (n=97) were diagnosed at nine public hospitals, and the controls (n=222) were recruited at institutions for children with DS. Odds ratios (OR) were calculated. RESULTS: Asthma was positively associated with AL development (OR=4.18; 95% confidence interval (CI): 1.47-11.87), whereas skin allergies were negatively associated (OR=0.42; 95% CI: 0.20-0.91). CONCLUSION: Our findings suggest that allergies and AL in children with DS share biological and immune mechanisms. To our knowledge, this is the first study reporting associations between allergies and AL in children with DS.

Factors increasing mortality in Echinococcosis patients treated percutaneously or surgically. A review of 1,143 patients: a retrospective single center study.

OBJECTIVE: While cystic echinococcosis (CE) is a serious problem in underdeveloped countries, it also becomes a serious public health problem in developed countries due to recent migration and population movements. This study aimed to investigate the relationship between pregnancy, multi-organ involvement, treatment methods, and emergency surgery (unfollowed patients), with mortality in patients with CE who underwent surgical or percutaneous treatment. PATIENTS AND METHODS: In this study, demographic characteristics, pregnancy status, organ involvement, development of relapse and anaphylaxis, need for intensive care and mortality rates of patients with CE treated with percutaneous or surgical methods at Harran University Hospital between January 1997 to January 2022 were investigated. RESULTS: Of the 1,143 patients who underwent surgery or percutaneous treatment for CE, 18 were pregnant. Mortality was found to be significantly higher in pregnant patients with CE (p<0.001). Mortality was significantly higher in those who developed anaphylaxis (p<0.001). In percutaneous treatment, recurrence (p<0.001) and anaphylaxis (p=0.026) were found to be significantly higher. Mortality was found to be three times higher in patients without follow-up who were operated on urgently (p=0.108). CONCLUSIONS: CE is a disease that can occur at any age and can be fatal. Although multi-organ involvement and percutaneous treatment may be associated with recurrence, they do not directly increase mortality. The mortality is high, especially in pregnant women with pulmonary CE. Cardiac involvement, brain involvement and anaphylaxis increase mortality. Mortality is higher in patients without follow-up who are operated on urgently.

DNA damage and changes in oxidized biomolecules in COVID-19 patients treated in intensive care units: a single center experience.

OBJECTIVE: COVID-19 is a deadly disease. Investigations are being conducted on the underlying mechanisms to predict prognosis and reduce mortality rates. In this study, the extent of DNA damage and serum levels of oxidized biomolecules were investigated. We hypothesize that malondialdehyde (MDA) and protein carbonyl (PC) serum levels and DNA damage levels may be biomarkers that can be used in prognostic decision making and prediction of mortality in COVID-19 patients. PATIENTS AND METHODS: Patients included in the study were divided into two groups according to their survival. These groups were compared in terms of serum MDA, PC levels, DNA damage degrees and mortality on the 1st, 3rd, and 5th days of ICU admission. RESULTS: In patients who died, MDA levels increased over time (p=0.023), PC levels peaked on the third day of admission to the intensive care units (ICU), and then decreased, while DNA damage increased gradually (p=0.013). In surviving patients, MDA levels decreased over time (p=0.018); PC levels were at their peak on the first day of admission to the ICU and then decreased (p=0.018); DNA damage decreased initially, and then increased minimally compared to Day 1. CONCLUSIONS: For COVID-19 ICU patients, serum levels of MDA and PC and degrees of DNA damage can strengthen prognostic decision-making and contribute to reducing mortality.

Comparison of cytotoxic, reactive oxygen species (ROS) and apoptotic effects of propofol, thiopental and dexmedetomidine on liver cells at accumulative doses (AML12).

OBJECTIVE: Propofol, thiopental and dexmedetomidine are hypnotic, sedative, antiepileptic and analgesic agents used in general anesthesia and intensive care. There are many known and yet unknown side effects. Our aim in this study was to examine and compare the cytotoxic, reactive oxygen species (ROS) and apoptotic effects of propofol, thiopental and dexmedetomidine drugs, which are widely used in anesthesia, on liver cells (AML12) in vitro. MATERIALS AND METHODS: The half-maximum inhibitory concentration (IC50) doses of the three drugs on AML12 cells were determined using the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) method. Then at two different doses of each of the three drugs, apoptotic effects were determined by the Annexin-V method, morphological examinations were determined by acridine orange ethidium bromide method and intracellular reactive oxygen species (ROS) levels were determined by flow cytometry. RESULTS: The IC50 thiopental, propofol and dexmedetomidine doses were found to be 255.008, 254.904 and 34.501 µgr/mL, respectively (p<0.001). The highest cytotoxic effect on liver cells was found in the lowest dose of dexmedetomidine (34.501 µgr/mL) compared to the control group. This was followed by thiopental and propofol, respectively. CONCLUSIONS: In this study, propofol, thiopental and dexmedetomidine drugs on AML12 cells were found to have toxic effects by increasing intracellular ROS at two different concentrations higher than clinical doses. It was determined that cytotoxic doses caused an increase in ROS and induced apoptosis in cells. We believe that the toxic effects of these drugs can be prevented by examining the values obtained from this study and the results of future studies.

Human decidual stromal cells secrete C-X-C motif chemokine 13, express B cell-activating factor and rescue B lymphocytes from apoptosis: distinctive characteristics of follicular dendritic cells.

BACKGROUND: Decidual stromal cells (DSCs) have classically been considered fibroblastic cells, although their function, cell lineage and origin are not fully understood. We previously demonstrated that human DSCs showed similarities with follicular dendritic cells (FDCs): DSCs expressed FDC-associated antigens, both types of cells are contractile and both are related to mesenchymal stem cells (MSCs). To further characterize DSCs, we investigated whether DSCs and FDCs share any distinctive phenotypical and functional characteristics. METHODS: Human FDC lines were obtained from tonsillectomy samples, human DSC lines from elective termination of pregnancy samples and human MSC lines from bone marrow aspirates. We isolated DSC, FDC and MSC lines and compared their characteristics with flow cytometry and enzyme-linked immunosorbent assay. Cell lines were cultured with tumour necrosis factor (TNF) and lymphotoxin (LT)α(1)ß(2), cytokines involved in FDC differentiation. Cell lines were also differentiated in culture after exposure to progesterone and cAMP, factors involved in the differentiation (decidualization) of DSC. RESULTS: Like MSCs, DSCs and FDCs expressed MSC-associated antigens (CD10, CD29, CD54, CD73, CD106, α-smooth muscle actin and STRO-1) and lacked CD45 expression, and all three types of cell line showed increased expression of CD54 (ICAM-1) and CD106 (VCAM-1) when cultured TNF and LTα(1)ß(2). DSCs and FDCs, however, exhibited characteristics not observed in MSCs: DSCs expressed FDC-associated antigens CD14, CD21 and CD23, B cell-activating factor and secreted C-X-C motif chemokine 13. Moreover, DSC lines but not MSC lines inhibited the spontaneous apoptosis of B lymphocytes, a typical functional attribute of FDC. During culture with progesterone and cAMP, FDCs, like DSCs but in contrast to MSCs, changed their morphology from a fibroblastic to a rounder shape, and cells secreted prolactin. CONCLUSIONS: Our results suggest that DSCs and FDCs share a common precursor in MSCs but this precursor acquires new capacities when it homes to peripheral tissues. We discuss these shared properties in the context of immune-endocrine regulation during pregnancy.