Role of melatonin in carcinogenesis and metastasis: From mechanistic insights to intermeshed networks of noncoding RNAs.

In recent years, seminal studies have been devoted to unraveling the puzzling mysteries associated with the cancer preventive/inhibitory role of melatonin. Our current knowledge of the translational mechanisms and the detailed structural insights have highlighted the characteristically exclusive role of melatonin in the inhibition of carcinogenesis and metastatic dissemination. This mini-review outlines recent discoveries related to mechanistic role of melatonin in prevention of carcinogenesis and metastasis. Moreover, another exciting facet of this mini-review is related to phenomenal breakthroughs linked with regulation of noncoding RNAs by melatonin in wide variety of cancers.

Gender-related variation expressions of neuroplastin TRAF6, GluA1, GABA(A) receptor, and PMCA in cortex, hippocampus, and brainstem in an experimental epilepsy model.

Epileptic seizures are seen as a result of changing excitability balance depending on the deterioration in synaptic plasticity in the brain. Neuroplastin, and its related molecules which are known to play a role in synaptic plasticity, neurotransmitter activities that provide balance of excitability and, different neurological diseases, have not been studied before in epilepsy. In this study, a total of 34 Sprague-Dawley male and female rats, 2 months old, weighing 250-300 g were used. The epilepsy model in rats was made via pentylenetetrazole (PTZ). After the completion of the experimental procedure, the brain tissue of the rats were taken and the histopathological changes in the hippocampus and cortex parts and the brain stem were investigated, as well as the immunoreactivity of the proteins related to the immunohistochemical methods. As a result of the histopathological evaluation, it was determined that neuron degeneration and the number of dilated blood vessels in the hippocampus, frontal cortex, and brain stem were higher in the PTZ status epilepticus (SE) groups than in the control groups. It was observed that neuroplastin and related proteins TNF receptor-associated factor 6 (TRAF6), Gamma amino butyric acid type A receptors [(GABA(A)], and plasma membrane Ca2+ ATPase (PMCA) protein immunoreactivity levels increased especially in the male hippocampus, and only AMPA receptor subunit type 1 (GluA1) immunoreactivity decreased, unlike other proteins. We believe this may be caused by a problem in the mechanisms regulating the interaction of neuroplastin and GluA1 and may cause problems in synaptic plasticity in the experimental epilepsy model. It may be useful to elucidate this mechanism and target GluA1 when determining treatment strategies.

Evaluation of the anticarcinogenic effects of Rutin on brain tissue in mice with Ehrlich ascites carcinoma by micro-computed tomography and histological methods.

BACKGROUND: Studies for new treatment strategies on cancer continue, and new searches continue in the diagnosis and evaluation of cancer. This study examined the possible anticarcinogenic effect of Rutin on the brain tissues of male mice with Ehrlich ascites carcinoma (EAC). MATERIAL AND METHODS: We used micro-computed tomography (micro-CT) and histologically Hematoxylin&Eosin (H&E) staining methods for evaluation. RESULTS: In the evaluation results, we saw a significant decrease in the brain volume of the tumor group to the control group. The difference in volume between the Rutin treatment group and the control group was not significant. In the brain tissues of the tumor group, numerous degenerated neurons characterized by pericellular/perivascular space expansion, cell swelling, or expansion were detected in the cortex and hippocampus regions. We showed a reduction in the damage rate in the Rutin treated group. CONCLUSION: As a result, Rutin was found to have an anticarcinogenic effect. In addition to the classical histological evaluation, we used a newer method, micro-CT, in our study. We believe that this study has important results both in terms of its originality and adding new information to the literature.

The effect of ionizing radiation on the fetal bone development in pregnant rats: Role of melatonin.

Radiation has been widely used in many business sectors over the last century. Our study investigated the possible teratogenic effects of radiation on the bones of rat fetuses and the protective effect of melatonin against these effects. In this study, 15 pregnant female Wistar albino rats were used. These rats were divided into four groups: the control group, melatonin group (10 mg/kg/day), radiation group (0.5 gray), radiation (0.5 gray) + melatonin group (10 mg/kg/day), and sham group (1 mm hanks/day). The skeletal system development of fetuses was examined with double skeletal and scanning electron microscope (SEM), histopathological methods. In our study, fetal weight, placental weight, and fetal morphometric values were found to be statistically significantly decreased in the radiation group compared to the control group (p < .05). In immünohistochemistry (IHC) analysis, alkaline phosphatase, and tartrate-resistant acid phosphatase) concentrations were found to be significantly lower in the radiation group compared to the other groups. In the SEM analysis, it was observed that the amount of calcium and sodium decreased when the radiation group was compared with the other groups. As a result, when exposed to ionizing radiation during pregnancy, melatonin has a protective feature against the negative effects of radiation on the bone development of fetuses. RESEARCH HIGHLIGHTS: In our study, fetuses obtained from pregnant rats exposed to ionizing radiation were examined. In this study, the effect of melatonin on bone development in fetuses exposed to gray ionizing radiation was investigated. There are few studies on our subject in the literature. We believe that our findings will contribute to other planned studies.

The effect of Cornus mas extract on nicotine-induced oxidative stress and intratesticular damage in male rats.

The role of oxidative stress in disease pathogenesis has been extensively investigated. Researchers have gathered sufficient evidence related to oxidative stress-mediated intratesticular damage. The aim of this was study to evaluate the effects of Cornus Mas (CM) extract on intratesticular changes in rats exposed to nicotine. Thirty Wistar albino rats were divided into four groups. The groups and the administrated agents for 35 days were as follows; Control group (n=6): 0.9% saline, intraperitoneally; Nicotine group (n=7): 4 mg/kg nicotine, subcutaneous; CM group (n=7): 1000 mg/kg CM extract in 0.5 ml saline, via gavage; Nicotine + CM Group (n=8): 4 mg/kg Nicotine, subcutaneous + 1000 mg/kg CM extract via gavage. One rat each from the groups Nicotine and CM died.  In spermatogenetic and histopathological examination, significant positive changes were detected in nicotine + CM group regarding seminal parameters, apoptotic cells, Factor VIII and Johnsen score as compared to nicotine group. Oxidative stress markers were higher in nicotine group as compared to the control group. OSI and MDA levels were found to be reduced in nicotine + CM group than nicotine group. Nicotine induced a significant increase in TNF-α and IL-6 levels compared to the control group; however, CM effectively counteracted this increase. We have shown that nicotine increases testicular damage, causes apoptosis of testicular cells and adversely affects spermatogenesis by increasing inflammation. We concluded that CM extract exerted beneficial effects on spermatogenesis and minimized testicular parenchymal damage, apoptosis and angiogenesis. Rapidly increasing understanding of the complexity of oxidative stress in intratesticular is the key to unlocking the potential of ROS-targeting therapies.

Can endoplasmic reticulum stress observed in the PTZ-kindling model seizures be prevented with TUDCA and 4-PBA?

Epilepsy is a chronic neurological disease with recurrent seizures. Increasing evidence suggests that endoplasmic reticulum (ER) stress may play a role in the pathogenesis of epilepsy. We aimed to investigate the effects of Tauroursodeoxycholic acid (TUDCA) and 4-phenyl-butyric acid (4-PBA), which are known to suppress ER stress, on developed seizures in terms of markers of ER stress, oxidative stress, and apoptosis. The pentylenetetrazole (PTZ) kindling model was induced in Wistar albino rats (n = 48) by administering 35 mg/kg PTZ intraperitoneally (I.P.) every other day for 1 month. TUDCA and 4-PBA were administered via I.P. at a dose of 500 mg/kg dose. ER stress, apoptosis, and oxidative stress were determined in the hippocampus tissues of animals in all groups. Immunohistochemistry, qRT-PCR, ELISA, and Western Blot analyzes were performed to determine the efficacy of treatments. Expressions of ATF4, ATF6, p-JNK1/2, Cleaved-Kaspase3, and Caspase12 significantly increased in PTZ-kindled seizures compared to the control group. Increased NOX2 and MDA activity in the seizures were measured. In addition, stereology analyzes showed an increased neuronal loss in the PTZ-kindled group. qRT-PCR examination showed relative mRNA levels of CHOP. Accordingly, TUDCA and 4-PBA treatment suppressed the expressions of ATF4, ATF6, Cleaved-Caspase3, Kaspase12, NOX2, MDA, and CHOP in TUDCA + PTZ and 4-PBA + PTZ groups. ER stress-induced oxidative stress and apoptosis by reducing neuronal loss and degeneration were also preserved in these groups. Our data show molecularly that TUDCA and 4-PBA treatment can suppress the ER stress process in epileptic seizures.

Tauroursodeoxycholic Acid (TUDCA) Regulates Inflammation and Hypoxia in Autonomic Tissues of Rats with Seizures.

Inflammation and hypoxia have an effect on the molecular mechanism of cardiovascular and respiratory pathologies accompanying seizures. Against this, Tauroursodeoxycholic Acid (TUDCA) can regulate oxidative stress, inflammation and cellular survival by suppressing endoplasmic reticulum (ER) stress. We evaluated the expression changes of NF-κB p65, TNF-α, HIF1α and Kir6.2 proteins associated with seizures in brain stem, heart and lung tissues representing the autonomous network. Additionally, we examined the protective effects of TUDCA administration against damage caused by seizures in terms of immunohistochemistry and pathology. 4 groups of Wistar Albino male rats (250-300 g, n=32) were formed as control, pentylenetetrazole (PTZ), TUDCA and PTZ+TUDCA. The epilepsy kindling model was created by intraperitoneal (i.p.) injection of PTZ chemical (35 mg/kg, every 2 days) for one month. TUDCA (500 mg/kg; every 2 days) treatment was given intraperitoneally 30 minutes before seizures for 1 month. Brain stem, heart (atria, ventricle) and lung tissues of rats were isolated. NF-κB p65, TNF-α, HIF1α and Kir6.2 proteins in the obtained tissues were evaluated by immunohistochemical staining. The immunoreactivity of the investigated proteins in the brainstem heart and lung tissues of rats with chronic PTZ administration was significantly increased. Recurrent seizures led to accumulation of inflammatory cells in tissues, hemorrhage, vasodilation, and apoptosis. Following TUDCA administration, expression of NF-κB p65, TNF-α and Kir6.2 was significantly reduced in all tissues (except the atrium of the heart) compared to control rats. HIF-1α levels were significantly suppressed in ventricular and lung tissues of epileptic rats given TUDCA. However, TUDCA pretreatment improved histopathological changes due to chronic seizures and partially reduced apoptosis. We showed that epileptic seizures may cause tissue damage with the development of inflammatory and hypoxic conditions in the brainstem and organs that represent the autonomic network. TUDCA therapy could be an effective agent in the treatment of cardiac and respiratory problems associated with seizures.

Evaluation of the protective role of resveratrol against sepsis caused by LPS via TLR4/NF-κB/TNF-α signaling pathways: Experimental study.

The development and progression of sepsis are multifactorial and influence the immunological, endocrine, and cardiovascular systems of the body. Our knowledge of the key mechanisms involved in the pathogenesis of sepsis has expanded exponentially, yet this still needs to be translated into effective targeted therapeutic regimes. In the present study, we aimed to determine whether resveratrol has positive effects in the experimental sepsis rat model. Twenty-eight male Spraque-Dawley rats were randomly divided into four groups (n = 7) as follows: control, lipopolysaccharide (LPS) (30 mg/kg dose), resveratrol, and LPS and resveratrol. After the experiment, liver and kidney tissues were collected for histopathological evaluation, blood serums were collected to measure malondialdehyde levels with enyzme-linked immunosorbent assay, and Toll-like receptor-4 (TLR4), tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) immunoreactivity density was evaluated immunohistochemically. In addition, messenger RNA expression levels for TLR4, TNF-α, NF-κB, interleukin-1ß, and interleukin 6 were measured. In addition, the damage observed in liver and kidney tissue was determined by AgNOR (argyrophilic nucleolar organizer regions) staining. LPS application caused severe tissue damage, oxidative stress, and increased the expressions of proinflammatory proteins and genes we evaluated, while resveratrol application eliminated these negativities. Resveratrol has been proven to suppress the TLR4/NF-κB/TNF-α pathway, a possible therapeutic signaling pathway that is important in initiating the inflammatory response in an animal model of sepsis.

Immunoreactivity of Kir3.1, muscarinic receptors 2 and 3 on the brainstem, vagus nerve and heart tissue under experimental demyelination.

AIMS: Demyelination affects the propogation of neuronal action potential by slowing down the progression. This process results in a neuro-impairment like Multiple Sclerosis (MS). Evidence show that MS also contributes to involvement of the autonomic system. In the molecular approach to this involvement, we aimed to observe muscarinic ACh receptor 2-3 (mAChR2-3), and inwardly rectifying potassium channel 3.1 (Kir3.1) immunoreactivities on the brainstem, vagus nerve, and heart under cuprizone model. MAIN METHODS: Wistar albino rats were randomly divided into 8 groups; duplicating 4 groups as male and female: control groups (n = 3 +3), Cuprizone groups (n = 12 +12), sham groups (n = 4 +4), and carboxy-methyl-cellulose groups (n = 3 +3). Cuprizone-fed rats underwent demyelination via Luxol fast blue (LFB) staining of the hippocampus (Gyrus dentatus and Cornu Ammonis) and cortex. Immunohistochemistry analysis followed to the pathologic measurement of the brainstem, vagus nerve, and heart for mAChR2, mAChR3 and Kir3.1 proteins KEY FINDINGS: A significant demyelination was observed in the hippocampus and cortex tissues of rats in the female and male cuprizone groups. Myelin basic protein immunoreactivity demonstrated that cuprizone groups, in both males and females, had down-regulation in the hippocampus and cortex areas. The weights of the cuprizone-fed rats significantly decreased over six weeks. Dilated blood vessels and neuronal degeneration were severe in the hippocampus and cortex of the cuprizone groups. In the female cuprizone group, expression of mAChR2 and mAChR2 was significantly increased in the brainstem, atrium/ventricle of heart, and left/right sections of vagus nerve. Kir3.1 channels were also up-regulated in the left vagus nerve and heart sections of the female cuprizone group SIGNIFICANCE: Especially in our data where female-based significant results were obtained reveal that demyelination may lead to significant mAChR2, mAChR3 and Kir3.1 changes in brainstem, vagus nerve, and heart. A high immunoreactive response to demyelination at cholinergic centers may be a new target.

Determination of Rutin's antitumoral effect on EAC solid tumor by AgNOR count and PI3K/AKT/mTOR signaling pathway.

Rutin is one of the flavonoids found in fruits and vegetables. The PI3K/AKT/mTOR signaling pathway is critical for the life cycle at the cellular level. In current study, we purposed to demonstrate the antitumoral effect of rutin at different doses through the mTOR-signaling pathway and argyrophilic nucleolar regulatory region. EAC cells were injected subcutaneously into the experimental groups. 25 and 50 mg/kg Rutin were injected intraperitoneally to the animals with solid tumors for 14 days. Immunohistochemical, Real-time PCR and AgNOR analyzes were actualized on the taken tumors. When the rutin given groups and the tumor group were compared, the tumor size increase was detected to be statistically significant (p < 0.05). In immunohistochemical analysis, a significant decrease was encountered in the AKT, mTOR, PI3K and F8 expressions especially in the groups administered 25 mg Rutin, in comparison with the control group (p < 0.05). AgNOR area/nuclear area (TAA/NA) and average AgNOR number were determineted, and statistically important differences were detected between the groups in terms of TAA/NA ratio (p < 0.05). There were significant statistical differences between the mRNA quantity of the PI3K, AKT1 and mTOR genes (p < 0.05). In the in vitro study, cell apoptosis was evaluated with different doses of annexin V and it was determined that a dose of 10 µg/mL Rutin induced apoptosis (p < 0.05). In our study, it was demonstrated in vivo and in vitro that Rutin has an anti-tumor effect on the development of solid tumors formed by both EAC cells.

Detection of melatonin protective effects in sepsis via argyrophilic nucleolar regulatory region-associated protein synthesis and TLR4/NF-κB signaling pathway.

In this study, the protective effect of melatonin was investigated in lipopolysaccharide induced sepsis model. Twenty-eight rats were randomly divided: Control, Melatonin, LPS and LPS + Melatonin. After LPS application, surgically remove kidney and liver tissues. The level of malondialdehyde (MDA) an oxidative stress marker and the immunoreactivity of Toll-like receptor-4 (TLR4), tumor necrosis factor-α (TNF-α), and transcription factor NF-κB were evaluated immunohistochemically. Expression levels for TLR4, TNF-α, NF-kB, IL-1ß (interleukin 1 beta), and IL-6 (interleukin 6) were evaluated. Additionally, Argyrophilic NOR staining was performed in tissues. Vacuolization and inflammation were more intense in the kidney and liver sections in the LPS group compared to the other groups. It was observed that vacuolization and inflammation were decreased in LPS + Melatonin applied groups. It was determined that glomerular damage was increased in the LPS and LPS-melatonin groups, but the damage rate LPS-Melatonin group was decrease in the LPS group. It was determined that the MDA level in tissues of the LPS group was importantly increased compared to other groups. Additionally, TAA/NA ratio statistically significant differences were discovered between the groups. This study supports the potential protective effects of 10 mg/kg melatonin by modulating critical markers of local immune reaction in a model of LPS-induced sepsis.

Inhibition of Ehrlich ascites carcinoma growth by melatonin: Studies with micro-CT.

Melatonin is a versatile indolamine synthesized and secreted by the pineal gland in response to the photoperiodic information received by the retinohypothalamic signaling pathway. Melatonin has many benefits, such as organizing circadian rhythms and acting as a powerful hormone. We aimed to show the antitumor effects of melatonin in both in vivo and in vitro models through the mammalian target of rapamycin (mTOR) signaling pathway and the Argyrophilic Nucleolar Regulatory Region (AgNOR), using the Microcomputed Tomography (Micro CT). Ehrlich ascites carcinoma (EAC) cells were administered into the mice by subcutaneous injection. Animals with solid tumors were injected intraperitoneally with 50 and 100 mg/kg melatonin for 14 days. Volumetric measurements for the taken tumors were made with micro-CT imaging, immunohistochemistry (IHC), real-time polymerase chain reaction (PCR) and AgNOR. Statistically, the tumor tissue volume in the Tumor+100 mg/kg melatonin group was significantly lower than that in the other groups in the data obtained from micro-CT images. In the IHC analysis, the groups treated with Tumor+100 mg/kg melatonin were compared when the mTOR signaling pathway and factor 8 (F8) expression were compared with the control group. It was determined that there was a significant decrease (p < 0.05). Significant differences were found in the total AgNOR area/nuclear area (TAA/NA) ratio in the treatment groups (p < 0.05). Furthermore, there were significant differences between the amount of mTOR mRNA for the phosphatidylinositol 3-kinase (PI3K), AKT Serine/Threonine Kinase (PKB/AKT) genes (p < 0.05). Cell apoptosis was evaluated with Annexin V in an in vitro study with different doses of melatonin; It was observed that 100 µg/mL melatonin dose caused an increase in the apoptotic cell death. In this study, we have reported anti-tumor effects of melatonin in cell culture studies as well as in mice models. Comprehensive characterization of the melatonin-mediated cancer inhibitory effects will be valuable in advancing our fundamental molecular understanding and translatability of pre-clinical findings to earlier phases of clinical trials.

Bone development in offspring of pregnant rats treated with carbamazepine: Evaluation by three different methods.

OBJECTIVE: This study was carried out to determine the effect of intrauterine carbamazepine (CBZ) exposure on fetal bone development during pregnancy. METHODS: In the study, 24 female Wistar pregnant rats were used. Rats were 20 weeks old. They had an average body weight of 150-200 g. Pregnant rats were randomly selected and divided (n = 6) into a control group, low-dose CBZ (10 mg/kg/day) group, medium-dose CBZ (25 mg/kg/day) group, and high-dose CBZ (50 mg/kg/day) group. The ossification length (mm) and ossification area (mm2 ) of the long bones of the fetuses in the experimental and control groups were calculated. The densities of alkaline phosphatase (AP) and tartrate-resistant acid phosphatase (TRAP) were analyzed. The ossification regions of the femurs of the fetuses were examined under a light microscope. Microstructural images of the femurs were evaluated with scanning electron microscope photographs. The densities of minerals involved in the ossification process were analyzed. RESULTS: According to the results of the study, all three doses of CBZ caused loss of ossification areas, and it was observed that this bone loss also increased statistically significantly depending on the dose increase (p < .05). Calcium concentration decreased in the CBZ groups. When the electron microscope images were examined, it was determined that the cartilage matrix of the CBZ groups was thinned. In the histological evaluation of the groups, narrowing of the primary bone collar and smaller bone spicules in the ossification region compared to the control group were noted due to the increase in dose in the CBZ groups. In immunohistochemical staining, it was observed that the TRAP and AP expression values of the femurs were the lowest in the CBZ groups. These decreases were also statistically significant when compared with the control group. SIGNIFICANCE: It was revealed with both microscopic and macroscopic findings that exposure to intrauterine CBZ negatively affected ossification and bone growth.

Clinical-practice stress levels and factors affecting these on first-year nursing students.

PURPOSE: This study aimed to determine the stress levels of first-year nursing students end of the first day of clinical practice and the factors affecting these. DESIGN AND METHODS: This was a descriptive and cross-sectional study. A student information form and the clinical stress questionnaire (CSQ) were used to collect the research data. FINDINGS: The average CSQ score of the students was 23.57 ± 8.35 and it was determined that the students experienced below-average stress. PRACTICE IMPLICATIONS: In line with the results obtained from the study, it was observed that the student's CSQ scores at the end of the first day of clinical practice were below average, and their biggest fear about clinical practice was that they would harm the patient.

Cerebral ischemia reperfusion injury: from public health perspectives to mechanisms.

Cerebral ischemia/reperfusion injury has emerged as an intricate mechanism. However, identification of wide-ranging mechanisms which mechanistically regulate reperfusion injuries have significantly improved our understanding. Recent advancements in our knowledge about the molecular consequences of ischemia and reperfusion might be advantageous in the development of innovative therapeutic strategies for the treatment of patients with ischemia and reperfusionassociated organ dysfunction and tissue inflammation. Some of the extensively studied mechanisms of reperfusion injury consist of oxidative stress, mitochondrial mechanisms, infiltration of leukocytes, activation/aggregation of the platelets, complement activation, and disruption of the blood-brain-barrier (BBB), which eventually results in the brain oedema or haemorrhagic transformations. In this review, we have attempted to provide a review of the protein networks involved in the regulation of cerebral ischemia reperfusion injury and how different natural products have shown potential in the amelioration of reperfusion induced injuries.

The effect of antioxidants in Ehrlich Ascites Cancer.

A fundamental goal in molecular oncology is to unravel the underlying mechanisms which cause the cell transformation. In line with this approach, genome-wide functional screening approaches have revealed exciting insights into heterogeneous nature of cancer. Rapidly expanding horizons of research have unraveled myriad of pathways which play instrumental role in carcinogenesis and metastasis. Oxidative stress has also been reported to be significantly involved in cancer onset and progression. In line with this approach, oxidative stress modulating chemicals have always been sharply divided into antioxidants and oxidative stress-inducing agents. Conceptual and experimental advancements have enabled us to critically analyze full potential of these two different groups of chemicals in cancer chemoprevention. Different antioxidants are currently being analyzed in different phases of clinical trials. Although it has been reported in the literature that antioxidant supplements reduce tumor cells in some tumors or cause volume reduction in solid tumor sizes, there is no definite consensus. Therefore, an antioxidant supplement guideline based on more detailed clinical research and as a result of these is needed to achieve the best care for cancer patients and to avoid risky treatments for cancer patients.

Mechanistic role of DANCR in the choreography of signaling pathways in different cancers: Spotlight on regulation of Wnt/ß-catenin and JAK/STAT pathways by oncogenic long non-coding RNA.

Discovery of non-coding RNAs has paradigmatically shifted our understanding of the multifaceted nature of cancer. It is becoming progressively more understandable that long non-coding RNAs play fundamental role in regulation of cell signaling pathways in different cancers. DANCR has started to gain remarkable appreciation because of its central role in cancer onset and progression. In this review we have attempted to summarize emerging aspects of DANCR-mediated regulation of Wnt/ß-catenin and JAK/STAT pathways in different cancers. We have also discussed how DANCR epigenetically inactivated tumor suppressors to promote cancer. There is sufficient experimental evidence related to oncogenic role of DANCR in variety of cancers. However, there is a need to uncover how DANCR modulates various other oncogenic pathways in different cancers.

Quality indicators for blood culture: 1 year of monitoring with BacT/Alert Virtuo at a French hospital.

Introduction. Blood culture (BC) remains the gold standard for the diagnosis of bloodstream infection. Clinical microbiology laboratories must ensure the quality of their BC process from receipt to definitive results.Aim. In this study, we followed the evolution of different quality indicators for BCs over the first year of implementation of the BacT/Alert Virtuo system in a French hospital.Methodology. In our laboratory, we instituted regular monitoring of several quality indicators to track (i) delays in sample registration, (ii) delays in loading BC bottles in our incubating system (BacT/Alert Virtuo) after registration, (iii) the volume of blood in bottles and (iv) the contamination rates.Results. For 53 892 BC bottles loaded in the BacT/Alert Virtuo from 23 January to 31 December 2019, the delays in sample registration, loading and unloading were respectively 3.5 h±0.016, 44 min±0.209 and 5.8 h±0.0727. Intriguingly, the automated process performed by the BacT/Alert Virtuo system to check the blood volume in bottles was only performed for 60 % of the loaded bottles. Among these, 30 % contained the recommended volume of blood (between 7 and 13 ml). Finally, the contamination rate was found to be 27.2 % for samples at our institution.Conclusions. The delays in sample registration, loading and unloading were found to be acceptable, even though they could be improved by ensuring a continuous service during the night duty period. Furthermore, the percentage of volumes measured is insufficient and must be improved and the majority of bottles do not contain the recommended blood volume.

The protective role of melatonin against the effects of different doses of caffeine on the fetus.

Skeletal system and some organs development changes in rat fetuses with 30 and 60 mg/kg caffeine and melatonin's (10 mg/kg) protective role against rat fetuses were investigated. Groups (n = 4) were formed as Control, LDC, HDC, LDC+melatonin, HDC+melatonin and melatonin. Fetuses were taken by cesarean section and stained using dual skeletal staining method and FESEM. TRAP and AP immune-reactivity concentrations were calculated.  Oxidative stress and inflammatory markers were also measured by liver, bone and placenta samples.  TNF-α, IL-1ß, IL-6, VEGF-A, SOST and Fetuin-A levels were measured in tissue by using ELISA. TBARS, SOD, GSH, GSSG, TOS, TAS, measured by spectrophotometric assay method.  The mRNA levels of Agtr2 gene expressed in placental tissues of control rats and in placental tissues of rats exposed to HDC, LDC, MEL, HDC+MEL, LDC+MEL were analyzed by Real-time PCR. The gene expressions of Agtr2 were significantly upregulated in the placentas exposed to HDC, MEL, HDC+MEL and LDC+MEL (P<0,001). No significant difference in samples of the LDC group (P>0,05). According to these data, caffeine used during pregnancy delayed ossification; melatonin, a powerful antioxidant, was found to eliminate this effect. Besides, changes in angiotensin receptor expression observed in response to a caffeine and melatonin exposure result from high dose and join effect.