Development of Orally Applicable,Combinatorial Drug–Loaded Nanoparticles for the Treatment of Fibrosarcoma

Nanoparticulate systems have been receiving a significant attention especially for the treatment of cancer but one of the main hurdles is to produce these developed and high-tech nanosystems in large quantities. Anticancer drug formulations are generally designed for parenteral administrations but oral administration is still the most convenient route. In this study, orally applicable nano-sized chitosan nanoparticles (NPs) were successfully prepared using Nano Spray Dryer. It is possible to produce these NPs in large quantities by simply increasing the processing time using the machine without changing any parameter. A chemotherapeutic agent (imatinib mesylate; IMA) and nonsteroidal anti-inflammatory drug (dexketoprofen trometamol) were loaded together in these NPs. NPs were also functionalized with polyethylene glycol and folic acid to obtain long circulating NPs and tumor targeting. The antitumoral activities of formulations showed that these developed NPs can enhance the effectiveness. Animal experiments were performed on fibrosarcoma-bearing mice model, and the treatment with 0.8 mg/μL/kg IMA-loaded chitosan NPs was found to be successful to slow down the growth of tumors. The tumor tissues were removed from the animals and enzymatic activities were evaluated. The inhibitory effect of tyrosine kinase was found to be enhanced from 36.4% to 68.4% when IMA was used in combination with dexketoprofen trometamol. Furthermore, all dried NPs were found to be stable for more than a year at 25°C. Presented results show that these developed combinatorial drug–loaded NPs can be used for the treatment of fibrosarcoma, and these data can provide an insight, new strategies for productions or alternatives in cancer treatment.     

The effect of saliva contamination on microleakage of an etch-and-rinse and a self-etching adhesive

PURPOSE: To evaluate the effect of saliva contamination on the microleakage of an etch-and-rinse adhesive and a self-etching adhesive. MATERIALS AND METHODS: Class V cavity preparations at the cementoenamel junction were made on the buccal and lingual surfaces of 40 freshly extracted human molars. The teeth were randomly assigned into two groups for different adhesives: Group I, Single Bond (two-step etch-and-rinse adhesive) and Group II, Futura Bond NR (one-step self-etching adhesive). The adhesive materials were applied according to their manufacturers' recommendations. The specimens were then further subdivided into five subgroups (A-E; n = 8): group A, contamination before adhesive curing; group B, contamination before adhesive curing and re-application of adhesive; group C, contamination after adhesive curing; group D, contamination after adhesive curing and re-application of adhesive; and group E, no contamination (control). Contamination of adhesive surfaces was performed with fresh natural saliva and the saliva was removed by a gentle air blast. The specimens were restored with Z250 hybrid composite. After thermocycling (500x, 5 degrees C to 55 degrees C) and immersion in 0.5% basic fuchsin, the dye penetration was evaluated under a stereomicroscope. Statistical analysis was performed with the Kruskal-Wallis test at p < 0.05. RESULTS: No statistically significant differences were found among the contamination subgroups on the enamel or on the dentin for either group (p > 0.05). There was no significant difference in leakage between Group I and Group II for any subgroup (p > 0.05). CONCLUSION: Contamination of adhesives with saliva before and after adhesive curing did not worsen the microleakage of the two-step etch-and-rinse adhesive Single Bond or the one-step self-etching adhesive Futura Bond NR.     

Lower vitamin D level is associated with poor coronary collateral circulation

Objectives. Vitamin D regulates calcium and bone homeostasis, and parathyroid hormone (PTH) secretion. Cross-sectional associations between lower vitamin D levels and cardiovascular diseases have been reported, but the relationship between vitamin D levels and collateral arteries in stable coronary artery disease (CAD) has not been reported before. Design. Two hundred and fourteen patients with above 95% stenosis in at least one epicardial coronary artery were consecutively recruited after coronary angiography (CAG) during the winter season. The coronary collateral circulation (CCC) was graded using Rentrop classification. Poor CCC group included patients with Rentrop Grade 0–1 CCC and control group included patients with Rentrop Grade 2–3 CCC. Vitamin D and PTH levels were measured on the day of CAG. Results. In the poor CCC group, vitamin D levels were lower (34 ± 25 pmol/L vs. 49 ± 33 pmol/L; p = 0.01) and the prevalence of vitamin D deficiency (< 37 pmol/L) was higher (67% vs. 43%; p = 0.01) compared to the controls. PTH levels, calcium, and phosphate levels were not significantly different between the groups. Female gender, lower HDL cholesterol, and lower vitamin D levels were independently correlated with poor CCC in the study population. Conclusion. Lower vitamin D levels may be associated with poor collateral development in patients with stable CAD.     

Change in amputation rate in a Turkish diabetic foot population

Diabetic foot, an important cause of morbidity and mortality, is an important economic problem in all countries. We examined the duration of diabetes, ratio of hospitalization, and the amputation rates of our diabetic foot patients between 1996 and 2002 and compared the results with those obtained between 1985 and 1995. Medical reports of 117 patients with diabetic foot referred to Gazi University Medical Faculty between 1996 and 2002 were retrospectively analyzed. The mean age was 61.09+/-10.87 years and mean duration of diabetes was 16.14+/-9.44 years. Sixty-one patients were hospitalized and 56 patients were followed in our outpatient clinic. The mean duration of hospitalization was 45.00+/-18.74 (20-74) days in amputees and 28.95+/-11.61 (10-47) days in the nonamputees (P=.023). The mean age and duration of diabetes were significantly higher in amputees in the present group than that in the previous group. The amputation rate was significantly lower in the group studied between 1996 and 2002 compared to the group followed between 1985 and 1995 (9.4% vs. 21%, respectively, P<.001). Appropriate diabetes education and systematic follow-up in an outpatient clinic may delay preventable diabetic foot lesions and reduce the amputation rate.     

Clinical and angiographic features of large left main coronary artery aneurysms

Coronary artery aneurysms are defined as coronary dilatations which exceed the diameter of normal adjacent segments by 1.5 times. Left main coronary artery (LMCA) is the least frequently involved artery with a prevalence of 0.1%. Majority of coronary artery aneurysms are atherosclerotic in origin. Their size and clinical presentation is variable. A number of complications have been reported to occur during the course of the disease including thrombosis and distal embolization, myocardial ischemia and/or infarction, dissection, vasospasm, calcification, fistulization and very rarely rupture. Large aneurysms of LMCA represent a potentially fatal condition even without concomitant atherosclerotic coronary disease. Because of rarity of coronary artery aneurysms, it is difficult to standardize treatment. In this article, we presented 4 cases of large LMCA aneurysms with various clinical and angiographic features.     

Serum galectin-3 level in systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disease of unknown etiology characterized by progressive fibrosis. Activated fibroblasts are mainly responsible for fibrosis in SSc. Galectin-3, a β-galactoside-binding lectin, plays many important regulatory roles in both physiological and pathological processes including proliferation, apoptosis, inflammation, and fibrosis. The purpose of this study was to assess the serum galectin-3 levels in patients with SSc. Thirty-seven SSc patients, 23 systemic lupus erythematosus (SLE) patients (serving as patient control group), and 28 healthy volunteers were enrolled in this study. Disease activity and severity scores were detected with Valentini disease activity index and Medsger disease severity scale in the SSc group and SLE disease activity index and Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index in the SLE group. The serum levels of galectin-3, vascular endothelial growth factor, transforming growth factor-β, and interleukin-6 were determined. Compared to the control group, the galectin-3 levels were higher in the SSc and SLE groups. The galectin-3 levels were not correlated with the disease activity and severity indexes in both patient groups. But, the serum galectin-3 levels were higher in the active SSc and SLE subgroups than in the inactive SSc (4.6?±?5.8 vs. 1.3?±?1.1 ng/ml, p?=?0.015) and SLE (17.4?±?11.3 vs. 6.5?±?8.9 ng/ml, p?=?0.019) subgroups. These results suggest that galectin-3, which is associated with fibrosis and inflammation by previous studies, may be a prominent biomarker of disease activity in SSc.     

The effect of preoperative anxiety on postoperative analgesia and anesthesia recovery in patients undergoing laparascopic cholecystectomy

Purpose

In patients who are hospitalized for surgery, anxiety disorders are frequently observed. Anxiety affects the patient’s perception of postoperative pain and has a negative impact on recovery from anesthesia. This study attempted to compare the effect of preoperative anxiety on postoperative pain control and recovery from anesthesia in patients undergoing laparoscopic cholecystectomy.

Methods

A total of 80 patients were enrolled who were undergoing laparoscopic cholecystectomy. Demographic characteristics of the patients were recorded. Beck’s anxiety ?nventory (BAI) was administered to the patients: patients with anxiety were included in the high-anxious patient group (group H) and patients without anxiety were enrolled in the low-anxious group (group L). Duration of surgery, duration of anesthesia, extubation time, and adverse effects were recorded. During the postoperative period, patient-controlled analgesia with tramadol was used for pain control. Visual analog scale (VAS) scores and tramadol consumption of all patients were recorded.

Results

Among all patients, 31 (38.75 %) patients had preoperative anxiety, and significant correlation was found between the days of hospitalization and preoperative score of BAI. In group L, extubation time, the time for the modified Aldrete score to reach 9, was seen as significantly shorter and fewer postoperative side effects were determined. Also in group L, postoperative VAS score and tramadol consumption were significantly lower, and less tenoxicam was needed.

Conclusion

A high preoperative anxiety level negatively affects recovery from anesthesia and control of postoperative pain. In this patient group, the increased need for postoperative analgesia must be adequately met.