In vitro inhibition of uterine contractions using electrospun nanofibers loaded with nifedipine and ML7.

OBJECTIVE: To formulate a nanofiber-based controlled drug delivery system that could be effective in preventing uterine contractions and can be used for the treatment of preterm labor. PATIENTS AND METHODS: We utilized uterine tissue samples obtained from ten pregnant women who underwent cesarean section at term to investigate the effect of nanofibers on spontaneous and induced myometrial contractions. We prepared nifedipine and ML7-loaded nanofibers using the electrospinning method with Poly(D,L-lactide-co-glycolide) (PLGA) polymer, resulted in seven groups of nanofibers, including a control group. Group I served as the control, Group II was non-drug loaded nanofiber, Group III was nifedipine (10-5 M) loaded nanofiber, Group IV was ML7 (3x10-5 M) loaded nanofiber, Group V was ML7 (3x10-5 M) and nifedipine (10-5 M) nanofiber, Group VI was ML7 (3x10-5 M) and nifedipine (3x10-5 M) nanofiber, and Group VII was ML7 (3x10-5 M) and nifedipine (10-4 M) nanofiber. To evaluate the contractile response, the nanofibers loaded with different doses of ML7 and nifedipine were applied onto the tissue strips, and in vitro organ bath experiments were performed. Full-thickness uterine samples were cleared of the serosa and surrounding tissues, and eight strips (3x10 mm) were prepared from each sample. The seven different nanofiber formulations were gently placed and sutured onto the strips, with one strip always kept as the time control. We recorded spontaneous, KCl-induced, and stimulated cumulative oxytocin-induced contractions from all samples in all groups. After completing all experiments, the viability of the strips was checked, and weight measurement was recorded. RESULTS: The administration of drug-loaded polymers resulted in a significant decrease in both the frequency and intensity of spontaneous and induced contractions in all groups (p<0.01). No significant difference was observed between the control group and the non-drug-loaded nanofiber group in post hoc analysis (p=0.704). In terms of amplitude and frequency of contractions, the most significant decrease was observed in group VII at cumulative oxytocin doses compared to the control and non-drug-loaded nanofiber groups (p<0.05). Moreover, group VI also showed a significant decrease in contraction intensity and frequency compared to the control and non-drug-loaded nanofiber groups (p<0.05). While the use of nifedipine and/or ML7-loaded nanofibers decreased both intensity and frequency of contraction, this attenuation was not significant compared to the control and empty polymer groups. However, a more significant inhibition was observed when ML7 was used with nifedipine at doses of 3x10-5 M and 10-4 M. CONCLUSIONS: The results indicate that human uterine contractions can be inhibited using calcium channel blocker (nifedipine) and myosin light chain kinase inhibitor (ML7) loaded nanofibers in uterine tissue strips. These results strongly suggested the potential for the development of locally effective and safe controlled drug release systems to prevent premature birth.

18F-fluorodeoxyglucose PET/computed tomography in locoregional staging and assessment of biological and clinical aggressiveness of breast cancer subtypes.

OBJECTIVE: We aimed to evaluate the availability of fluorine-18-fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) in initial axillary lymph node (ALN) staging in breast cancer. The secondary objective is to evaluate the role of FDG PET/CT as a pretest in sentinel lymph node biopsy vs. axillary lymph node dissection when predicting disease aggressiveness. METHODS: The study evaluated retrospectively 194 breast cancer patients who underwent preoperative 18F-FDG. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of FDG PET/CT for ALN metastases were confirmed with histopathology as the gold standard. RESULTS: The value of the area under curve (AUC), sensitivity and specificity for ALN metastases were determined as 0.847, 78.8% and 92.6%, respectively. The cut-off value of the maximum standardized uptake value (SUVmax) for metastatic ALN detection was calculated as 1.79. PPV, NPV and the accuracy of 18F-FDG PET/CT were 0.933 (93.3%), 0.75 (75%) and 0.837 (83.7%), respectively. The SUVmax value of the primary lesion was significantly correlated with grade, estrogen receptor (ER) status, progesterone receptor (PR) status, SUVmax value of metastatic ALN, Her-2 status and Ki-67 level. Molecular subtypes revealed no statistically significant difference in terms of mean SUVmax value. CONCLUSION: High values of AUC, sensitivity, specificity, NPV and PPV encourage utilization of PET/CT for locoregional staging of nonmetastatic breast carcinoma. The significant correlation between the primary tumor SUVmax value and grade, ER status, PR status and Ki-67 level increases the prognostic predictive value of the preoperative PET/CT.

Squamous cell carcinoma arising from teratoma of the ovary: magnetic resonance, computed tomography, and pathological findings.

In the present case report, the authors investigated the clinicopathological characteristics of squamous cell carcinoma (SCC) arising from teratoma of the ovary and intended to report their clinical experience. Malignant transformation of ovarian teratoma is a quite rare condition with SCC observed to be the most common form of transformation. The present case was a 43-year-old female patient and her clinical presentation was abdominal pain, abdominal distension, and abdominal mass sensation. The patient underwent ultrasonography. After detection of a mass, magnetic resonance imaging (MRI) was performed. Surgery was performed on the patient and the pathological report revealed SCC arising from teratoma. The patient was evaluated retrospectively in terms of demographic characteristics, MRI, surgical findings, and prognosis.

VITAMIN DEFICIENCY AND INSULIN RESISTANCE IN NONDIABETIC OBESE PATIENTS.

OBJECTIVE: Obese people may have nutritional deficiencies, although they are exposed to excessive food intake. We aim to assess relationship of vitamin D, B12, and folic acid levels and dietary vitamin intake and insulin resistance in obese people. DESIGN: This case-control study was performed at the obesity outpatient clinics between March 2014 and April 2015. SUBJECTS AND METHODS: We included 304 non-diabetic obese subjects in patient group and 150 normal weight individuals in control group. Patients were questioned in detail about their food intake. RESULTS: Mean age of obese patients was 37.3±10.1 years, the mean duration of obesity was 7.9±5.4 years, and the percentage of female patients was 65.8%. Mean vitamin D, B12, and folic acid levels were significantly lower in patients than in controls. Vitamin D deficiency (<20 ng/mL) in 69.7%, vitamin B12 deficiency (<200 pg/mL) in 13.5%, and folic acid deficiency (<4 ng/mL) was found in 14.2% of the patients. BMI negatively correlated with vitamin D, B12, and folic acid levels. B12 levels negatively correlated with duration of obesity. Insulin resistance was found in 55.9% of patients and HOMA-IR levels negatively correlated with vitamin D and B12 levels. While dietary vitamin D and folic acid intakes were inadequate in all of patients, only 28.3% of patients had inadequate vitamin B12 intake. There was no relation between vitamin levels and dietary vitamin intakes. CONCLUSIONS: The study reveals that vitamin D, B12, and folic acid levels were low and poor vitamin D and B12 status were associated with insulin resistance in nondiabetic obese patients.

Realization of magnetic resonance current density imaging at 3 tesla.

Magnetic Resonance Current Density Imaging (MRCDI) is an imaging modality, which reconstructs electrical current density distribution inside a material by using Magnetic Resonance Imaging (MRI) techniques. In this study, a current source with maximum current injection capability of 224.7mA, under 1kΩ resistive load is used. Experiments are performed with a 2D uniform phantom, in which a current steering insulator is inserted. Magnetic flux density distributions are measured, and current density images are reconstructed. The reconstructed images are in agreement with the reconstructions obtained with simulated measurements.

Pre-operative arterial embolization of symptomatic giant hemangioma of the liver.

The cavernous hemangiomas of the liver are usually small sized and asymptomatic. Most of them are incidentally diagnosed and a very small portion requires therapy. Giant hemangioma can be symptomatic, and this condition is the indication for treatment. The striking complication of surgical treatment of cavernous hemangiomas is intra-operative bleeding. In this case, we aimed to demonstrate that the risk of intraoperative bleeding can be eliminated with the preoperative percutaneous trans-catheter arterial embolization technique.

Toxic nuclear effects of the organophosphorus insecticide Dichlorvos (DDVP) in human peripheral blood lymphocytes.

Organophosphorus insecticides are used worldwide in the control of agricultural, household and veterinary pests. Dichlorvos (2,2-dichlorovinyl dimethyl phosphate) is a commonly used organophosphorus insecticide. In this study, in order to elucidate the toxic nuclear effects of dichlorvos, freshly isolated human peripheral blood lymphocytes were incubated with 5, 10, 20, 40, 80 and 100 microg/mL of dichlorvos. According to the results, dichlorvos induced micronuclei, decreased the mitotic and replication indexes. It is a genotoxic product causing chromosomal damage (an increase in micronucleus) and cell death (decrease in mitotic and replication indexes).

QSAR of genotoxic active benzazoles.

Previously synthesized 2,5-disubstituted benzoxazole and benzimidazole derivatives, were tested for their genotoxic activity in the Bacillus subtilis rec- assay. The results revealed that 5-methyl-2-(p-aminobenzyl)benzoxazole exhibited the highest genotoxic response, which was comparable to 4-nitroquinoline 1-oxide (4-NQO), the reference agent of classical positive mutagen. Among the other tested compounds, four showed a genotoxic activity. A QSAR study revealed that structural parameters IY(C(2)H(4)) and IY(CH(2)O), indicating the bridge elements between the phenyl moiety and the fused ring system at position 2 and the quantum chemical parameter (DeltaE ), showing the difference between HOMO and LUMO energies, were found significant for enhancing the genotoxic activity in these compounds. In addition, the substituent effects on positions R and R(1) were found important for the activity as well as holding a substituent possessing a maximum length with a minimum width property on position R(1) like alkyl groups. On the other hand, substituting position R with an electron donating group instead of electron withdrawing group increased the genotoxic activity.

Genotoxic potential of Turkish propolis in peripheral blood lymphocytes.

Propolis is a natural product that is collected by the honeybee (Apis mellifera L.) from plants. The in vitro genotoxic potential of propolis in human lymphocytes was investigated. Blood samples were obtained from ten healthy (five female and five male), non-smoking and alcohol volunteers, which were incubated and exposed to increasing concentrations of propolis (5, 25, 50 and 250 mg/ml). The mean sister chromatid exchange (SCE) rates were 10.398 +/- 1.47-21.522 +/- 2.08. The differences between the control and exposed cells were statistically significant (p < 0.05). Increasing SCE rates showed that propolis could have genotoxic effects in high concentrations. SCE rates of women donors exceeded those of men donors. Women donors had the highest SCE rates (25.674 +/- 8.71, 22.456 +/- 7.97 and 15.756 +/- 5.09 for mean of SCE).

Synthesis, characterization and mutagenicity of new cis-[Pt(2-substituted-benzimidazole)2Cl2] complexes.

In this study, four new platinum(II) complexes with the structures cis-[Pt(Ligand)2Cl2] (ligand = 2-(p-methoxy-/or-p-chlorobenzyl or p-methoxyphenyl)benzimidazol (1, 2, 4 respectively) and 5(6)-methyl-2-phenoxymethylbenzimidazole (3) were synthesized and characterized by their elemental analysis, and IR and 1H NMR spectra. The potentials of the Pt(II) complexes for short-term bacterial mutagenicity were tested in reverse-mutation assays using Salmonella typhimurium frame-shift strain T 98 and S. typhimurium TA 100 and TA 102 strains, which carry mutations particularly sensitive to reversion by DNA base-pair substitution. The tests were performed in the absence of S9 rat liver fraction. Among the complexes tested 1 had no mutagenic activity. Complex 4 was found to be weakly mutagenic in TA 98 only. The Pt(II) complexes 2 and 3 were found to be mutagenic in TA 98, TA 100 and TA 102.

The in-vitro and in-vivo characterization of PLGA:L-PLA microspheres containing dexamethasone sodium phosphate.

Dexamethasone sodium phosphate (DSP) is a widely used corticosteroid in the treatment of brain oedema associated with brain tumours. DSP has many side effects that limit its usage at an effective concentration. The objective of this study was to minimize these side effects by encapsulating DSP using biodegradable synthetic polymers, to extend the release time from microspheres and to evaluate the effectiveness in the treatment of brain oedema. Microspheres containing 5% DSP were formulated by the solvent evaporation method by using a 1:1 mixture of two synthetic polymers, poly(lactic-co-glycolic acid) and L-polylactic acid (PLGA and L-PLA). The surface morphologies and particle size distribution of the microspheres were investigated. The in-vitro release studies were performed in pH 7.4 phosphate buffer solution. For determining the effectiveness of microspheres in the treatment of brain oedema, Sprague-Dawley rats weighing 200-250g were used as an animal model. Brain oedema was generated by the cold lesion method, and the effectiveness of the microspheres in treatment of oedema was investigated by the wet-dry weight method, lipid peroxidation ratios and histological evaluations. The average particle size of the microspheres was 13.04 +/- 2.05 microm, and the in-vitro release time of the microspheres was 8 h for 100/release. The degree of oedema was significantly different from the control group for the wet-dry weight method and lipid peroxidation ratio (p < 0.05). Similarly, histological evaluation of the tissues shoved that degree of oedema was significantly decreased with respect to the control group. All these results showed that implantation of microspheres was significantly more effective with respect to the systemic administration of DSP.

Silent cerebral lesions on magnetic resonance imaging in subjects with coronary artery disease.

MRI of subjects with silent intracranial damages may provide more evidence than CT. Our objectives were to determine the prevalence of silent MRI lesions in patients with coronary artery disease. The study included 72 consecutive patients with angiographically proven coronary artery disease and 26 age and sex matched controls with normal coronary angiography. All subjects were evaluated for coronary atherosclerosis (Gensini and coronary angiography scores), the number of silent cerebral lesions detected by MRI, carotid stenosis and the risk factors for stroke. Thirty one of 72 (43.0%) patients had silent brain lesions on MRI while 8 of 26 (30.7%) control subjects showed silent brain infarction. The main finding on T2-weighted MRI was white matter hyperintensities (WMH) which were seen in all patients with silent brain lesions. The mean age of the patients with coronary artery disease and with silent cerebral lesions was significantly higher than that of patients without silent brain lesions. The Gensini score, coronary angiography score and prevalence of carotid stenosis are significantly higher in patients with silent cerebral lesions than that of patients without silent cerebral lesions. There was no significant difference between silent cerebral lesions and the other risk factors for stroke. Silent brain lesions are a common complication in patients with coronary artery disease. In patients with coronary artery disease, carotid artery stenosis and age were important risk factors for the development of silent brain infarction.