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.     

Quality of Life and Psychological Well-being in Children and Adolescents with Disorders of Sex Development

Objective:The aim of this study was to assess the quality of life (QoL) and psychological well-being in child and adolescent with disorders of sex development (DSD).Methods:Sixty-two cases, aged 2-18 years, who were followed by a multidisciplinary DSD team were included. All participants and their parents were requested the complete the Pediatric Quality Of Life Inventory (PedsQL) and the Strengths and Difficulties Questionnaire. The psychiatric diagnoses of the patients were evaluated according to Schedule for Affective Disorders and Schizophrenia for School-Age Children/Present and Lifetime Turkish Version.Results:There was no significant difference between the 46,XX DSD and 46,XY DSD groups for both child and parent in Total PedsQL score. In the subscale scores, the PedsQL Physical Functionality Score reported by children was significantly lower for the 46,XX DSD group than for the 46,XY DSD group (p=0.01). There was a psychiatric diagnosis in 25.8% of cases. The PedsQL School Functionality Score reported by children in the group with psychiatric diagnosis was significantly lower than the group without psychiatric diagnosis (p=0.018). In the group with psychiatric diagnosis, the PedsQL Total Score and the subscale scores (Emotional Functionality Score, Social Functionality Score, School Functionality) reported by parents were significantly lower than in parents of the group without psychiatric diagnosis.Conclusion:This study emphasized that psychiatric disorders in DSD patients negatively affect the QoL. Psychiatric support and counseling from a multidisciplinary team are very important for families affected by DSD.     

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.     

Molecular analysis in X-linked adrenoleukodystrophy patients: identification of a novel mutation

X linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease characterized by progressive demyelination of the central nervous system, adrenocortical insufficiency and elevated levels of very long chain fatty acids (VLCFAs). It is caused by mutations in ABCD1 gene located at Xq28. More than 1,300 mutations have been identified to date which is unique to each patient. In this study we report the mutational analysis of 2 X-ALD patients (1 male and 1 female) showing variable clinical spectrum. The mutation analysis of the female patient revealed IVS5-6delC (c.1489-6delC) and p. P543L variations in compound heterozygous state. The male patient was found to be hemizygous for a novel mutation, p. R104P. In conclusion, while defining a novel mutation, the cases presented herein may contribute to the mutation and clinical spectrum of X-ALD.     

Comparison of Sealer Penetration Using the EndoVac Irrigation System and Conventional Needle Root Canal Irrigation

Introduction

The aim of this study was to compare the effect of the EndoVac irrigation system (SybronEndo, Orange, CA) and conventional endodontic needle irrigation on sealer penetration into dentinal tubules.

Methods

Forty single-rooted, recently extracted human maxillary central incisors were randomly divided into 2 groups according to the irrigation technique used: conventional endodontic needle irrigation and EndoVac irrigation. All teeth were instrumented using the ProFile rotary system (Dentsply Maillefer, Ballaigues, Switzerland) and obturated with gutta-percha and AH Plus sealer (Dentsply DeTrey, Konstanz, Germany) labeled with fluorescent dye. Transverse sections at 1, 3, and 5 mm from the root apex were examined using confocal laser scanning microscopy. The total percentage and maximum depth of sealer penetration were then measured.

Results

Mann-Whitney test results showed that EndoVac irrigation resulted in a significantly higher percentage of sealer penetration than conventional irrigation at both the 1- and 3-mm levels (P < .05). However, no difference was found at the 5-mm level. The 5-mm sections in each group showed a significantly higher percentage and maximum depth of sealer penetration than did the 1- and 3-mm sections (P < .05).

Conclusions

The EndoVac irrigation system significantly improved the sealer penetration at the 1- to 3-mm level over that of conventional endodontic needle irrigation.     

The effects of different hernia repair methods on postoperative pain medication and CRP levels

Although tension-free techniques of hernia repair using synthetic meshes have yielded encouraging results, the best method of inguinal hernia repair is still unclear. The aim of this study was to compare the responses of inflammatory mediators and postoperative pain relief following laparoscopic total extraperitoneal (TEP) hernioplasty, open tension-free mesh hernioplasty (Lichtenstein), posterior preperitoneal mesh hernioplasty (Nyhus procedure), and Bassini procedure. Patients with primary inguinal hernia were randomized in the operating room to undergo one of these repair techniques. Group I comprised 24 patients treated by Lichtenstein procedure; Group II comprised 21 patients treated by Nyhus procedure; Group III comprised 19 patients treated by Bassini procedure; and Group IV comprised 20 patients treated by laparoscopic TEP mesh hernioplasty. Postoperative pain levels following hernia repair were compared by measuring the use of patient-controlled analgesia (PCA) during the 24 hours after surgery. Serum samples withdrawn before surgery and 48 hours after surgery were assayed for C-reactive protein (CRP) content. Patient characteristics, operating time, and operative and early complications were noted. Serum CRP levels rose markedly following Nyhus (184.5 +/- 41.6 mg/L), Lichtenstein (138.4 +/- 72.5 mg/L), and Bassini repair (137.2 +/- 55.9 mg/L) compared with that of patients who underwent TEP mesh hernioplasty (55.5 +/- 41.2 mg/L). There were also significant differences in the postoperative need for analgesics via PCA among patients undergoing Nyhus (382.9 +/- 189.1 mg), Bassini (303.2 +/- 173.7 mg), and Lichtenstein (253.9 +/- 129.3) procedures compared with 196.6 +/- 148.8 mg for the TEP mesh hernioplasty group. Patients in the Lichtenstein group also had significantly less need of analgesics than those in the Nyhus and Bassini groups. In conclusion, TEP mesh hernioplasty is less traumatic and yields less postoperative pain than the Nyhus, Lichtenstein, and Bassini procedures.     

The Relation between the Color M‐Mode Propagation Velocity of the Descending Aorta and Coronary and Carotid Atherosclerosis and Flow‐Mediated Dilatation

Background: To improve clinical outcomes, noninvasive imaging modalities have been proposed to measure and monitor atherosclerosis. Common carotid intima‐media thickness (CIMT) and brachial artery flow‐mediated dilatation (FMD) have correlated with coronary atherosclerosis. Recently, the color M‐mode‐derived propagation velocity of descending thoracic aorta (AVP) was shown to be associated with coronary artery disease (CAD). Methods: CIMT, FMD, and AVP were measured in 92 patients with CAD and 70 patients having normal coronary arteries (NCA) detected by coronary angiography. Patients with acute myocardial infarction, renal failure or hepatic failure, aneurysm of aorta, severe valvular heart disease, left ventricular ejection fraction <40%, atrial fibrillation, frequent premature beats, left bundle branch block, and inadequate echocardiographic image quality were excluded. Results: Compared to patients with normal coronary arteries, patients having CAD had significantly lower AVP (29.9 ± 8.1 vs. 47.5 ± 16.8 cm/sec, P < 0.001) and FMD (5.3 ± 1.9 vs. 11.4 ± 5.8%, P < 0.001) and higher CIMT (0.94 ± 0.05 vs. 0.83 ± 0.14 mm, P < 0.001) measurements. There were significant correlations between AVP and CIMT (r =−0.691, P < 0.001), AVP and FMD (r = 0.514, P < 0.001) and FMD and CIMT (r =−0.530, P < 0.001). Conclusions: The transthoracic echocardiographic determination of the color M‐mode propagation velocity of the descending aorta is a simple practical method and correlates well with the presence of carotid and coronary atherosclerosis and brachial endothelial function. (Echocardiography 2010;27:300‐305)