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.     

Intrafamilial variability of XYLT2-related spondyloocular syndrome

Spondyloocular syndrome is characterized by generalized osteoporosis, multiple fractures and severe ocular findings. The causative XYLT2 mutations have recently been identified with the use of whole exome sequencing. We report on two siblings with spondyloocular syndrome who presented with varying clinical severity. A novel XYLT2 missense mutation was detected in a region evolutionary conserved across the species. This report along with the previous reports demonstrates that variable expressivity may be possible even within the same family. These two siblings with a novel mutation further expand the clinical and mutational spectrum of spondyloocular syndrome.     

First description of the alpha lipoic acid intoxication in an adult patient worldwide following oral administration

Alpha lipoic acid (ALA), which is an anti-oxidant acting as a scavenger for reactive oxygen species, is especially used to improve glycemic control and prevent polyneuropathies associated with diabetes mellitus. ALA is considered to be a safe drug and intoxication with ALA is extremely rare. However, this paper reports a 38-year-old young woman who was admitted to the emergency department after she had ingested ten pills of 600 mg ALA belonging to her diabetic parent, which led to delirium, metabolic acidosis, thrombocytopenia, and rhabdomyolysis. To the best of our knowledge, there are only four cases of ALA intoxication reported in the literature and all were observed in children. This report aims to present the first case of ALA related intoxication worldwide in an adult patient.     

Increased serum sialic acid levels in primary osteoarthritis and inactive rheumatoid arthritis

Accumulation of oxidized proteins and impaired antioxidant system have been shown to be associated with arthritis. Serum sialic acid (SA) is known as a parameter of inflammation. In the present study, to explore the potential role of SA in arthritis, we measured serum SA levels, plasma protein oxidation, and antioxidant status in patients with primary osteoarthritis (POA) and inactive rheumatoid arthritis (RA). Inactive RA (iRA) was defined upon the American College of Rheumatology criteria for clinical remission of RA. A total of 40 patients (20 POA patients, including 4 male subjects, and 20 iRA female patients) and 20 healthy female subjects were included in this study. SA, antioxidants, and protein oxidation levels were determined spectrophotometrically in serum or plasma samples. Serum SA levels were significantly increased in POA (3.34 +/- 0.37 mM, p < 0.0001) and iRA (3.11 +/- 0.47 mM, p < 0.05), compared with healthy controls (2.41 +/- 0.16 mM). Plasma total antioxidant activity, plasma superoxide dismutase activity and serum reduced glutathione levels were significantly decreased in patients with POA and those with iRA, whereas plasma carbonyl content and serum total protein were increased in those patients. Moreover, plasma total thiol levels were significantly increased in iRA and decreased in POA. Thus, increased SA and protein oxidation levels are associated with the decreased antioxidant levels in POA and iRA patients. These results suggest that SA may be considered as a potent defense molecule against oxidative damage in arthritis. Antioxidant therapy may halt or ameliorate the progression of arthritis.     

Procalcitonin kinetics in pediatric patients with systemic inflammatory response after open heart surgery

Objective To evaluate procalcitonin and C-reactive protein as markers of inflammation severity and their value in predicting development of organ failure after pediatric open heart surgery.Design Prospective, observational, clinical study.Setting Single university hospital.Patients Thirty-three pediatric patients with systemic inflammatory response syndrome (SIRS; n = 19) and SIRS+organ failure (SIRS+OF; n = 14) following open heart surgery were included.Measurements and results Plasma procalcitonin and C-reactive protein levels were measured before and after the operation, and 1, 2, 3, and 4 days after surgery. Patients were evaluated daily to assess organ failure. Postoperative procalcitonin levels in the SIRS+OF group were significantly higher than in the SIRS group. C-reactive protein levels were similar between the groups throughout the study period. Peak procalcitonin levels were found to be positively correlated with aortic cross-clamp and cardiopulmonary bypass times, duration of mechanical ventilation, intensive care unit and hospital stay, mortality and organ failure development. Peak procalcitonin was found to be a good predictor of postoperative organ failure development and mortality. However, the predictive value of peak C-reactive protein for organ failure and mortality was found to be weak. Double-peak procalcitonin curves were observed in SIRS+OF patients with infection during the intensive care unit stay.Conclusion In the SIRS+OF group peak procalcitonin levels were found to be highly predictive for mortality and organ failure development, whereas C-reactive protein levels were not. Daily procalcitonin measurements in SIRS+OF patients may help identify the postoperative infection during the follow-up period.     

Correlation of the Tei index with left ventricular dilatation and mortality in patients with acute myocardial infarction

The Tei index is an echocardiographic index of combined systolic and diastolic function, calculated as isovolumetric relaxation time plus isovolumetric contraction time divided by ejection time. The aim of this study was to define the correlation of the Tei index with left ventricular dilatation and mortality in patients with acute myocardial infarction (AMI). A total of 77 patients (58 men, 19 women) with a mean age of 53 +/- 12 years, who had presented with an AMI in our clinic between June 2001 and February 2002 were compared with a control group of 88 healthy subjects (63 men, 25 women) with a mean age of 55 +/- 6 years. Echocardiographic evaluation was carried out within 24 hours and the third month of AMI, using a 3.5 MHz probe with pulse wave Doppler recordings by the adult cardiac mode of an Acuson C 256 echocardiograph. There were statistically significant differences between the 2 groups in all echocardiographic parameters, except mitral A wave. Thirteen patients died during the follow-up period of 3 months. The Tei index was significantly higher in the patients who died compared with those who survived (0.70 +/- 0.10 versus 0.61 +/- 0.10; P < 0.001). The patients who had heart failure after AMI had a mean Tei index value of 0.76 +/- 0.27, whereas the patients who did not have heart failure after AMI had a significantly lower Tei index value of 0.60 +/- 0.32 (P < 0.05). Patients were divided into 2 groups according to their Tei index. Patients with a > 0.60 Tei index had significantly higher end-systolic and end-diastolic volumes compared to patients with a < 0.60 Tei index (P < 0.001 for both) in the acute phase of AMI. Within 3 months, patients with a Tei index < 0.60 had a significant reduction in end-diastolic volumes (P < 0.01), whereas the end-diastolic volumes did not change significantly in patients with an index > 0.60 (P = 0.19). The Tei index is an important indicator of left ventricular dysfunction and death after AMI. A greater Tei index at the onset of AMI is associated with a higher incidence of subsequent cardiac death, CHF, and progressive LV remodeling.     

Adipokines and Systemic Inflammation in Weight-Losing Lung Cancer Patients

Background  

Cancer cachexia is a devastating condition leading to loss of function and independence, decreased performance status, decreased quality of life, and poor prognosis. Adipokines play a role in a wide variety of physiological or pathological processes, including immunity and inflammation, in addition to having significant effects on metabolism and lipogenesis. The objective of the present study was to investigate the relationship of adipokines and systemic inflammation in weight-losing advanced-stage non-small-cell lung cancer (NSCLC) patients.