In vitro release and In vivo biocompatibility studies of biomimetic multilayered alginate-chitosan/β-TCP scaffold for osteochondral tissue

Biomimetic three-layered monolithic scaffold (TLS) intended for the treatment of osteocondral defects was prepared by using alginate, chitosan and β-tricalcium phosphate (β-TCP) to study drug release behavior of the alternative drug delivery system and to investigate the therapeutic efficacy of the scaffold. Dexamethasone sodium phosphate (Dex) as a model drug was incorporated into the scaffold by solvent sorption method and in vitro release studies were conducted. In addition, the scaffold was implanted into the defects formed in the trochlea of Sprague–Dawley rats to assess the healing potential of the TLS on the osteochondral defect against reference Maioregen® comparatively. The release studies showed that after an initial burst at 3rd h, dexamethasone is released slowly during a 72-h period. In vivo studies indicated that the TLS has good tissue biocompatibility and biodegradation rate and showed better results during osteochondral healing process compared to the reference. All results demonstrated that the alginate-chitosan/β-TCP scaffold could be evaluated as a good candidate for osteochondral tissue applications.     

Immunohistochemical expression of PTEN in normal, hyperplastic and malignant endometrium and its correlation with hormone receptors, bcl-2, bax, and apoptotic index

PTEN is a tumor suppressor gene that is frequently mutated in type I endometrioid endometrial carcinomas (EECs), and is involved in the control of cell proliferation, differentiation, and apoptosis. In this study, we aimed to assess the relationship between PTEN expression and estrogen, progesterone receptors (PRs), other apoptosis-related proteins, such as bcl-2 and bax, and apoptotic index (AI) in EEC, its precursor lesion hyperplasia, and cyclical endometrium. We also evaluated the relationship between PTEN expression and clinicopathologic parameters. PTEN, estrogen receptor (ER), PR, and bcl-2 and bax expressions were evaluated immunohistochemically, and AI was evaluated in hematoxylin and eosin (HE)-stained slides in 23 cyclical and 37 hyperplastic endometria and in 35 EECs. PTEN expression was higher in cyclical endometrium than in the carcinomas (p<0.05). The PTEN expression level was significantly higher in non-atypical hyperplasias than in EEC, but there were no differences between atypical complex hyperplasia (ACH) and EEC and between hyperplasias. In the carcinomas, there was a negative correlation between grade and PTEN expression (r=-0.338, p=0.047). In conclusion, we presume that PTEN is involved in the early phases of endometrial tumorigenesis, and it can be speculated that decreased PTEN expression with loss of differentiation in carcinoma can contribute to the emergence of tumors with a more aggressive phenotype.     

Polymorphisms in the tumor necrosis factor-alpha gene in Turkish women with pre-eclampsia and eclampsia

The genetic background predisposing pregnant women to pre-eclampsia/eclampsia (PE/E) is still unknown. The aim of the current study was to investigate whether there is an association between the TNF-alpha-308 and 850 polymorphisms and PE or eclampsia. In this study, 40 cases of eclampsia, 113 cases of PE and 80 normotensive control cases were genotyped for the TNF-alpha-G-308A and C-850 polymorphisms. At position 308, the replacement of Guanine with Adenosine was denoted as TNF2. We found a significant difference between the TNF2 allele frequencies of the eclamptic, pre-eclamptic and normotensive controls. TNF2 (AA) polymorphism frequency was significantly higher among the eclamptics and pre-eclamptics (control : 5%, PE : 13.3%, E : 12.9%). A significantly different genotype distribution of C-850T polymorphism was observed between the PE/E and control groups, with the frequency of the variant TT genotype being significantly reduced in the preeclamptics (PE : 17% ; E : 17.5%) when compared with the control group (24.3%). We have demonstrated an association between TNF-alpha polymorphisms and pre-eclampsia susceptibility. However, it is not known whether C-850T polymorphism has a functional effect on the TNF-alpha gene. In addition, it was not possible to determine whether this polymorphism promotes the progression from PE to eclampsia because of no statistically significant difference between eclampsia and the controls.     

The effect of hepatitis C virus infection on insulin resistance in chronic haemodialysis patients

PURPOSE: To investigate the contribution of HCV infection to insulin resistance in chronic haemodialysis patients. MATERIALS AND METHODS: The study was performed with 55 patients who were on regular haemodialysis therapy three times per week. Of the 55 patients, 34 (20 females and 14 males with an average age of 40.9 years) were anti-HCV (+) and were defined as the HCV (+) group. The remaining 21 patients (8 females and 11 males with an average age of 50 years) were negative for HCV and other viral markers and were defined as the HCV (-) group. BMI of all patients were below 27. Insulin resistance (IR) was calculated according to the HOMA formula and patients were called HOMA-IR (+) if their HOMA scores were higher than 2.5. All of the HOMA-IR (+) patients in both groups were called the HOMA-IR (+) subgroup. None of the patients had a history of drug use or any diseases that were related to insulin resistance except uremia. In both groups and the healthy control group, insulin and glucose levels were studied at three different venous serum samples taken at 5- minute intervals after 12 hours of fasting. Other individual variables were studied at venous serum samples taken after 12 hours of fasting. RESULTS: HOMA scores were (3)2.5 in 22 of 34 HCV (+) patients (64.7%) and 7 of 21HCV (-) patients (33.33%) (p=0.024). Insulin levels of HCV (+) group (13.32 +/- 9.44mIU/mL) were significantly higher than HCV (-) (9.07 +/- 7.39mIU/mL) and the control groups (6.40 +/- 4.94mIU/ mL) (p=0.039 and p=0.021 respectively). HCV (+) patients were younger (40.94 +/- 17.06 and 52.62 +/- 20.64 years, respectively) and had longer dialysis duration (7.18 +/- 3.61 and 2.91 +/- 2.69 years, respectively). Significant positive correlations of HOMA score with insulin (r=0.934, p=0.000) and fasting glucose levels (r=0.379, p=0.043) were found in the HOMA- IR (+) subgroup. Also, a significant positive correlation was found between ALT and insulin levels in the HOMA IR (+) subgroup. C-peptide levels of both HCV (+) and (-) groups were significantly higher than the control group (p < 0.001). There were not any significant correlations between HOMA score and some of the other individual variables including levels of triglyceride, ferritin, ALT, iPTH and Mg in any of the groups. CONCLUSION: In chronic haemodialysis patients; HCV infection is related to a high prevalence of insulin resistance, higher insulin and glucose levels.     

Breast metastases from undifferentiated nasopharyngeal carcinoma

The most common primary tumours metastasising to the breast include melanoma, lymphoma, lung cancer and ovarian cancer, while metastases from head and neck cancer are rare. Metastases from undifferentiated nasopharyngeal carcinoma cancers are extremely rare, and only 3 well-documented cases have been reported in the English literature. We report a fourth case of breast metastases from nasopharyngeal carcinoma confirmed by in situ hybridization, focusing on clinical data as well as radiologic and pathologic features.     

Classification of carotid artery Doppler signals in the early phase of atherosclerosis using complex-valued artificial neural network

In this study, carotid arterial Doppler ultrasound signals were acquired from left carotid arteries of 38 patients and 40 healthy volunteers. The patient group had an established diagnosis of the early phase of atherosclerosis through coronary or aortofemoropopliteal angiographies. Results were classified using complex-valued artificial neural network (CVANN). Principal component analysis (PCA) and fuzzy c-means clustering (FCM) algorithm were used to make a CVANN system more effective. For this aim, before classifying with CVANN, PCA method was used for feature extraction in PCA-CVANN architecture and FCM algorithm was used for data set reduction in FCM-CVANN architecture. Training and test data were selected randomly using 10-fold cross validation. PCA-CVANN and FCM-CVANN architectures classified healthy and unhealthy subjects for training and test data with about 100% correct classification rate. These results shown that PCA-CVANN and FCM-CVANN classified Doppler signals successfully.     

Effects of Flutamide on [Methyl-H]-Choline Uptake in Human Prostate Cancer-3 Cells: A Pilot Study

Background: Positron emission tomography using [methyl-¹¹C]-choline is effective in imaging many types of cancer, especially prostate cancer (PC). The antiandrogen flutamide is often used as part of the initial treatment of PC. Data on the effect of flutamide on and methylcholine incorporation into PC-3 cells are lacking in the experimental and literature work.Objectives: The aims of this study were to assess whether human PC-3 cells are susceptible to flutamide and whether the drug modulates the uptake of [methyl-³H]-choline into these cells.Methods: PC-3 cells were treated for 3 days with flutamide (≤100 nmol/L), inhibiting growth by 20% to 70% with control cells included. Two viability tests (cytotoxic analyses), the thiazole blue assay and the trypan blue exclusion method, were used to determine the median inhibitory concentration for flutamide (10 nmol/L). Control and flutamide-treated cells were incubated with [methyl-³H]-choline for 10 minutes and then in nonradioactive medium for 10 minutes to simulate the rapid blood clearance of [methyl-¹¹C]-choline tracer that occurs within 5 to 20 minutes, and then extracted using organic and aqueous solvents to determine the intracellular distribution of the tracer. Protein assay and flow-cytometry analysis were used to determine protein content and DNA synthesis in both control and treated cells. The uptake of [methyl-³H]-choline was normalized to protein content and expressed as mean (SD) dpm/1Jg protein (n = 6).Results: PC-3 cell proliferation was inhibited with flutamide treatment. After treatment of PC-3 cells with flutamide 10 nmol/L for 3 days, cells accumulated DNA during the S phase. Mean (SD) [methyl-³H]-choline uptake was found to be significantly lower with flutamide 10-nmol/L-treated cells compared with control cells (65.95 [0.72] vs 114.21 [0.57] dpm/1Jg protein; P < 0.001); the difference between the 5-nmol/L-treated cells and controls was nonsignificant.Conclusions: In this pilot study, flutamide inhibited tumor cell growth and proliferation and decreased (modulated) the uptake of [methyl-³H]-choline into androgen receptor-negative PC-3 cells. These results suggest that flutamide might inhibit proliferation by an androgen-independent mechanism.     

Synthesis and pharmacological evaluation of pyrazolopyrimidopyrimidine derivatives: anti-inflammatory agents with gastroprotective effect in rats

We report the synthesis of new anti-inflammatory 1,7-dihydropyrazolo[3′,4′:4,5]pyrimido[1,6-a]pyrimidine 5 from aminocyanopyrazole. All compounds were characterized by physical, chemical and spectral studies. Preliminary pharmacological evaluation of the resulting products showed that compounds 5a, b, f (50–100 mg/kg, i.p) are active anti-inflammatory agents in carrageenan-induced rat paw oedema assay, and their effects are comparable to that of acetylsalicylic–lysine (300 mg/kg, i.p.), used as a reference drug. The nature of substituent (Y, R₃) had a pronounced effect on the anti-inflammatory activity. Studies of structure–activity relationships have led to selection of compound ethyl-3,5-dimethyl-7-imino-N ¹-phenyl-1,7-dihydropyrazolo[3′,4′:4,5]pyrimido[1,6-a]pyrimidine-6-carboxylate, 5f which exhibited the most potent anti-inflammatory activity. In addition, the compounds 5a, b, f showed a significant gastroprotective effect against HCl/EtOH-induced gastric ulcer.