Development of methylated cobalt-alkyne complexes with selective cytotoxicity against COX-positive cancer cell lines.

Derivatives of the cytotoxic cyclooxygenase (COX) inhibitor [(prop-2-ynyl)-2-acetoxybenzoate]dicobalthexacarbonyl (Co-ASS) with a methyl group in the 3, 4, 5, or 6 position of the acetylsalicylic acid (ASS) scaffold were synthesized with the aim to achieve enhanced selectivity for COX-2. From this modification, a higher specificity for COX-2-expressing tumors is expected, preventing COX-1-mediated side effects. The cobalt-alkyne complexes were tested for their COX-inhibitory and antiproliferative properties as well as their cellular uptake. Methylation reduced the effects at the isolated COX-1, whereas those at the isolated COX-2 remained nearly constant compared to Co-ASS. In cellular systems, the new compounds showed superior cytotoxicity toward the COX-positive HT-29 colon carcinoma cells than cisplatin. The reduced growth-inhibitory potency in T-24 cells, which express distinctly fewer COX enzymes (COX-1/COX-2 = 50/1) than HT-29 cells (COX-1/COX-2 = 50/50), and the only marginal activity in COX-negative MCF-7 breast cancer cells point to an interference in the arachidonic acid cascade through COX-2 inhibition as part of the mode of action, especially as the cellular uptake was even higher in MCF-7 cells than in T-24 cells. These findings clearly demonstrate that the methylated cobalt-alkyne complexes possess promising potential for further development as reasonable alternatives to the limited platinum-based antitumor agents.

Risk of late appearance of acute myocardial infartion after carbon monoxide (CO) intoxication / Riesgo de aparición de infarto agudo de miocardio en el largo plazo después de una intoxicación por monóxido de carbono (CO)

ABSTRACT Background: After acute carbon monoxide intoxication, there may be a higher risk for late adverse cardiac events. However, these patients are usually not followed to monitor the appearance of these effects. Aim: To follow patients seen at an emergency department for carbon monoxide intoxication, monitoring the appearance of myocardial infarction. To assess the predictive value for such complication of serum troponin, carboxyhemoglobin, and procalcitonin levels at the moment of intoxication. Material and Methods: We followed 237 patients receiving emergency care for carbon monoxide intoxication, with a serum carboxyhemoglobin of 5% or more, between 2010 and 2012. Levels of procalcitonin and troponin I were measured. Patients were followed for five years after the intoxication. Results: During the follow up period, 35 patients had a myocardial infarction. These patients had significantly higher carboxyhemoglobin, procalcitonin and troponin I levels at the moment of the intoxication than their counterparts who did not had a myocardial infarction in the follow up. A logistic regression analysis showed that age, carboxyhemoglobin levels, procalcitonin, troponin 1 and length of CO exposure were associated with a higher risk of myocardial infarction. Procalcitonin, troponin and carboxyhemoglobin levels had a high sensitivity and specificity to predict the appearance of myocardial infarction, with high areas under the receiver operating characteristic (ROC) curves. Conclusions: In patients with CO intoxication, carboxyhemoglobin, troponin and procalcitonin levels at the moment of the intoxication are significant predictors of the late appearance of myocardial infarction.

Antecedentes: Después de una intoxicación con monóxido de carbono, hay un mayor riesgo de desarrollar problemas cardiovasculares a largo plazo. Sin embargo, estos pacientes no son seguidos habitualmente para evaluar la aparición de estos eventos. Objetivo: Efectuar un seguimiento de pacientes que han sufrido una intoxicación con CO, evaluando la aparición de infarto del miocardio. Evaluar el valor de los niveles de troponina, carboxihemoglobina y procalcitonina para predecir la aparición de estos eventos. Material y Métodos: Seguimos 237 pacientes que fueron atendidos de urgencia por una intoxicación con CO, con niveles de carboxihemoglobina de 5% o más, entre 2010 y 2012. Se midieron los niveles de procalcitonina, troponina 1 y carboxihemoglobina y los pacientes fueron seguidos por cinco años después de la intoxicación. Resultados: Durante el seguimiento, 35 pacientes tuvieron un infarto al miocardio. Estos pacientes tenían niveles significativamente más altos de procalcitonina, troponina 1 y carboxihemoglobina al momento de la intoxicación, que los pacientes que no tuvieron un infarto durante el seguimiento. Una regresión logística mostró que la edad, carboxihemoglobina, procalcitonina, troponina y la duración de exposición a CO se asociaron a un mayor riesgo de infarto. Procalcitonina, troponina 1 y carboxihemoglobina tuvieron una alta sensibilidad y especificidad para predecir la aparición de infarto, con áreas bajo la curva ROC (receiver operating characteristic) elevadas. Conclusiones: En pacientes con intoxicación por CO, la carboxihemoglobina, procalcitonina y troponina son predictores significativos de la aparición de infarto agudo de miocardio en el largo plazo.

Do MCHC, MPV, and Procalcitonin Levels Determine Prognosis in Acute Coronary Syndrome?

AIM: Acute coronary syndrome (ACS) continues to be the main cause of mortality and morbidity globally. The aim was to assess serum procalcitonin (PCT), mean corpuscular hemoglobin concentration (MCHC) and mean platelet volume (MPV) levels in terms of complications after myocardial infarctus, triple vein coronary artery disease (TVCAD), and mortality prediction. MATERIAL AND METHOD: This cross-sectional cohort study included 200 patients with ACS attending the emergency department of our hospital with chest pain and admitted to the cardiology clinic from January 2014 to December 2016. Patients were divided into 4 groups as inferior group, anterior group, NSTEMI group, and UA group according to diagnosis. These groups were compared in terms of complications occurring after MI, TVCAD, and mortality rates. RESULTS: There were significant differences in terms of complications forming after ACS, TVCAD, and mortality. The inferior subgroup had high PCT and MCHC levels and was found to have more complications developing and mortality compared to other groups. Patients with high PCT and MPV values were identified to have higher mortality and TVCAD. In the anterior subgroup, ischemic heart failure was higher compared to the other groups. In the interior, anterior, and non-ST elevated myocardial infarctus (NSTEMI) groups, the 0-, 6-, and 12-hour cTnI values were significantly higher compared to the UA group, while the anterior group had a significantly higher 12-hour cTnI value compared to the NSTEMI group. Correlation analysis for PCT, MCHC, and MPV with complications developing after MI, mortality, and TVCAD found positive and statistically significant correlations. CONCLUSION: High PCT, MCHC, and MPV levels in acute coronary syndrome may be beneficial predictive values in terms of complications that may develop, TVCAD, and mortality.

Risk of late appearance of acute myocardial infartion after carbon monoxide (CO) intoxication.

BACKGROUND: After acute carbon monoxide intoxication, there may be a higher risk for late adverse cardiac events. However, these patients are usually not followed to monitor the appearance of these effects. AIM: To follow patients seen at an emergency department for carbon monoxide intoxication, monitoring the appearance of myocardial infarction. To assess the predictive value for such complication of serum troponin, carboxyhemoglobin, and procalcitonin levels at the moment of intoxication. MATERIAL AND METHODS: We followed 237 patients receiving emergency care for carbon monoxide intoxication, with a serum carboxyhemoglobin of 5% or more, between 2010 and 2012. Levels of procalcitonin and troponin I were measured. Patients were followed for five years after the intoxication. RESULTS: During the follow up period, 35 patients had a myocardial infarction. These patients had significantly higher carboxyhemoglobin, procalcitonin and troponin I levels at the moment of the intoxication than their counterparts who did not had a myocardial infarction in the follow up. A logistic regression analysis showed that age, carboxyhemoglobin levels, procalcitonin, troponin 1 and length of CO exposure were associated with a higher risk of myocardial infarction. Procalcitonin, troponin and carboxyhemoglobin levels had a high sensitivity and specificity to predict the appearance of myocardial infarction, with high areas under the receiver operating characteristic (ROC) curves. CONCLUSIONS: In patients with CO intoxication, carboxyhemoglobin, troponin and procalcitonin levels at the moment of the intoxication are significant predictors of the late appearance of myocardial infarction.

The evaluation of two genetic polymorphisms of paraoxonase 1 in patients with pulmonary embolism.

BACKGROUND AND OBJECTIVE: Pulmonary embolism (PE) is caused by some genetic factors for more than half patients. Paraoxonase 1 (PON1) has significant anti-oxidative and anti-inflammatory effects. According to our knowledge, there is no study researching the relation between PON 1 gene polymorphisms and PE in the literature. Therefore, it is aimed to research possible impacts of PON 1 Q192R and L55M polymorphisms on PE, considering anti-inflammatory and anti-oxidative effects of PON 1 in Turkish population. METHODS: One hundred and five PE patients and one hundred and seventeen controls were enrolled in this study. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses for the PON1 gene Q192R and L55M polymorphisms. RESULTS: Any associations were not found between clinical and demographical characteristics of PE patients and the PON1 gene Q192R polymorphism; however, there were associations between surgery, chronic renal failure, and cerebrovascular disease on the history of patients and L55M polymorphism (P = .013, P = .037, and P = .031, respectively). Genotype and allele frequencies did not show any significant differences between patients and controls according to PON1 gene Q192R and L55M polymorphisms (P > .05). CONCLUSION: The results of this study suggest that there is no correlation between PE and PON 1 gene Q192R and L55M polymorphisms in the Turkish population from the Central Black Sea region. Besides, whole genotypes and alleles of Q192R and L55M are not risk factors for patients with PE in this population.

In vivo effects of intravenous lipid emulsion on lung tissue in an experimental model of acute malathion intoxication.

Malathion can be ingested, inhaled, or absorbed through the skin, but acute toxicity is maximized when administered orally. Intravenous lipid emulsion (ILE) treatment is used as a new therapeutic method in cases of systemic toxicity caused by some lipid soluble agents. This study aimed to examine the potential treatment effect of ILE on rat lung tissue in a toxicokinetic model of malathion exposure. Twenty-one adult Wistar albino rats were randomly divided into three equal groups. The groups were organized as group I (control), group II (malathion), and group III (malathion + ILE treatment). Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were evaluated in lung tissues. Immunohistochemical and Western blot analyses were performed to determine the bax, bcl-2, and caspase-3 expression levels. Tissue GSH-Px and SOD activities were decreased and MDA levels were increased in the malathion group. ILE administration increased GSH-Px and SOD activity and decreased MDA levels compared to the malathion group. Furthermore, expression of bax, bcl-2, and caspase-3 significantly increased in the malathion group, and ILE infusion reduced these expression levels. The present study revealed that acute oral malathion administration increased oxidative stress and apoptosis in the lung tissue of rats. ILE infusion prevented oxidative stress and decreased the deleterious effects of malathion. Taken together, the findings of our study suggest that lipid emulsion infusion has treatment efficacy on malathion-induced lung toxicity.

Curcumin protects against acoustic trauma in the rat cochlea.

OBJECTIVES: In this study we evaluated the therapeutic utility of curcumin in a rodent model of acoustic trauma using histopathology, immunohistochemical, and distortion product otoacoustic emission (DPOAEs) measurements. METHODS: 28 Wistar albino rats were included in the study and randomly assigned to 4 treatment groups. The first group (group 1) served as the control and was exposed to acoustic trauma alone. Group 2 was the curcumin group. Group 3 was the curcumin plus acoustic trauma group. Group 4 was the saline plus acoustic trauma group. Otoacoustic emission measurements were collected at the end of the experiment and all animals were sacrificed. Cochlea were collected and prepared for TUNEL (TdT-mediated deoxyuridinetriphosphate nick end-labelling) staining assay. RESULTS: Group 3 maintained baseline DPOAEs values at 3000 Hz, 4000 Hz and 8000 Hz on the 3rd and 5th day of the experiment. DPOAEs results were correlated with the immunohistochemical and histopathological findings in all groups. In comparison to the histopathologic control group, Group 1 exhibited a statistically significant increase in apoptotic indices in the organ of Corti, inner hair cell, and outer hair cell areas (p < 0.05). Relative to the control group, rats in Group 3 showed little increase in inner hair cell and outer hair cell apoptotic indices. CONCLUSIONS: Our results support the conclusion that curcumin may protect the cochlear tissues from acoustic trauma in rats. Curcumin injection prior to or after an acoustic trauma reduces cochlear hair cell damage and may protect against hearing loss.

Caecum location in laboratory rats and mice: an anatomical and radiological study.

Intraperitoneal (i.p.) injection is the most frequently used method for implementing parenteral therapies in rats and mice. Whether the caecum is located in the right caudal quadrant or left caudal quadrant in the abdominal cavity is not clear. For that reason, we have developed a method for identifying the location of the caecum in rats and mice and thus revealed the most reliable location for i.p. injection in these animals. Two hundred Wistar albino rats and 100 BALB/c mice were used. The location of the caecum was determined by revealing the intra-abdominal organs immediately following euthanasia, photographing the organs, and archiving the images. Both digital photographic images and computed tomographic (CT) sections were analysed in terms of caecum morphology and location. In both rats and mice, the caecum was most commonly located on the animal's left side. It was less frequently located on the right side or in the centre. The caecum was typically comma-shaped, but it was round or S-shaped in some animals. The direction of rotation of the caecum from the basis to the apex was mostly counterclockwise. Additionally, the apex showed a tendency to be evenly centred. This study demonstrated that the caecum was mostly located on the animal's left side; and for that reason, the most suitable location for i.p. injection in these animals was understood to be the right caudal quadrant. Furthermore, when we compared the CT images and autopsy findings, the caecum did not change location in the abdominal cavity postmortem.