Design and synthesis of novel organometallic complexes using boronated phenylalanine derivatives as potential anticancer agents

Drug design and discovery studies are important because of the prevalence of diseases without available medical cures. New anticancer agents are particularly urgent because of the high mortality rate associated with cancer. A series of mononuclear gold (III) and platinum (II) complexes based on boronated phenylalanine (BPA) were designed and synthesized using 4,4’-dimethyl-2,2’-dipyridyl (L1) or 1,10-phenanthroline-5,6-dion (L2) ligands to obtain promising anticancer drug candidates. Proton nuclear magnetic resonance, infrared, mass spectrometry, and elemental analyses were utilized for chemical characterizations. Cell viability, cancer cell colony formation, endothelial tube formation, and cytoskeleton staining assays were performed using A549 lung adenocarcinoma and human umbilical vein endothelial cells (HUVECs) to investigate preliminary pharmacological activities. L1-based platinum (II) complex (BPA-L1-Pt) was the most promising complex, and has similar activity with the approved chemotherapy drug cis-platinum. Half maximal inhibitory concentration values for BPA-L1-Pt were 9.15 µM on A549s and 16.61 µM on HUVECs; the values for cis-platinum were 5.24 µM on A549s and 23.14 µM on HUVECs. Consequently, further synthesis studies should be performed to boost the cancer cell selectivity feature of BPA by varying metal and ligand types.     

Volume control associated with better cardiac function in long-term peritoneal dialysis patients.

BACKGROUND: This study was undertaken to investigate the effect of long-term blood pressure (BP) reduction, achieved with salt restriction and strict volume control, on frequency and regression of left ventricular hypertrophy (LVH) in long-term peritoneal dialysis (PD) patients. METHODS: 56 patients who had been treated for more than 2 years under our care were enrolled. After echocardiographic (Echo) evaluation, 46 patients were included in the follow-up study. In our unit, we aim to keep patients' BP below 130/85 mmHg and cardiothoracic index below 0.50. To reach these targets, moderate salt restriction is advised, and if necessary, hypertonic PD solutions are used. Echo was performed at the beginning of the study (after a mean period of 36 months on PD) and at the end of the prospective follow-up period (24 months later). RESULTS: At the time of the first Echo, LVH was detected in only 8 (21%) patients. Residual urine volume was significantly decreased compared to data taken when they first started PD (658 +/- 795 vs 236 +/- 307 mL/day). Mean left ventricular mass index (LVMI) was 107 +/- 26.5 g/m2. LVMI was significantly decreased at the end of the follow-up in patients who had LVH at baseline. No LVH developed in patients who had normal LVMI at baseline. CONCLUSION: Our results indicate that control of hypertension is possible when extracellular fluid volume is kept under control using hypertonic PD solutions in case of recruitment in addition to salt restriction in long-term PD patients. Sustained normovolemia is associated with low incidence and regression of LVH.     

Evaluation of Tc-99m(V) DMSA for imaging inflammatory lesions: An experimental study

The present study evaluated^99mTc(V) DMSA as an agent for the visualization of inflammatory lesions in comparison to^99mTc(HI) DMSA and^99mTc-HIG. All three radiopharmaceuticals were prepared with commercial kits.^99mTc(V) DMSA was prepared at neutral pH by the addition of first bicarbonate and then pertechnetate to the kit contents. The labeling efficiency was 99% as determined by ITLC. Abscesses were induced by i.m. injection of 50 μl turpentine into the right thighs of 36 Swiss albino mice. Six days later 3.7 MBq of each radiopharmaceutical was i.v. administered to 12 mice. The mice were sacrificed at 1,3,6 and 24 h later. Scintigrams were obtained with a gamma camera. The abscesses were better visualized on scintigrams with^99mTc(V) DMSA compared to^99mTc(III) DMSA, starting at 1 h. The animals were dissected and the organs were removed, weighed and the radioactivity determined with a gamma counter. The abscess to other tissue ratios were higher with^99mTc(V) DMSA than the other radiopharmaceuticals. The max. abscess/muscle ratios were 9.46 ± 3.20 (24 h), 4.19 ± 1.39 (6 h) and 5.98 ± 1.17 (24 h) and max. abscess/blood ratios were 6.22 ± 1.41, 4.09 ± 0.84 and 0.914 ± 0.351 all at 24 h for^99mTc(V) DMSA,^99mTc(III) DMSA and^99mTc-HIG, respectively. Experimental arthritis was produced in 6 New Zealand white rabbits by intra-articular injection of ovalbumin. Four days later 37 MBq of^99mTc(V) DMSA and^99mTc-HIG were each i.v. administered to 3 rabbits. Scintigrams obtained at 1, 3, 6, and 24 h clearly demonstrated arthritic joints. ROFs over arthritic joints were compared to contralateral normal joints (A/C). The max. A/C ratios were 2.10 ± 0.31 (3 h) and 2.92 ± 0.99 (24 h) for^99mTc(V) DMSA and^99mTc-HIG, respectively. Our results indicated the feasibility of imaging inflammatory lesions with^99mTc(V) DMSA.     

Stoma Adjustable Silicone Gastric Banding versus Vertical Banded Gastroplasty for the Treatment of Morbid Obesity

Background: Among gastric restrictive operations, the procedure of choice is still controversial. The aim of this study is to compare the results of two different gastric restrictive procedures: vertical banded gastroplasty (VBG) and stoma adjustable silicone gastric banding (ASGB). Methods: Between 1991 and 1996, 51 patients were treated surgically for morbid obesity: 27 underwent VBG and 24 underwent ASGB. Preoperative body weight (BW), body mass index (BMI) and percentage of ideal body weight (% IBW) were (mean ± SD): 145.7 ± 45.3 kg; 53.9 ± 15.9 kg/m²; 249.1 ± 73.5% respectively in the VBG group. Corresponding figures for the ASBG group were 132.5 ± 22.7 kg; 46.9 ± 7.8 kg/m² and 207.2 ± 35.0%. Results: In the VBG group, the median follow-up period was 26 months (range: 7-47). Eighteen months after the operation BW, BMI, % IBW and percentage of excess weight loss (% EWL) were 85.5 ± 26.8 kg, 31.9 ± 9.8 kg/m², 145.4 ± 43.9% and 74 ± 1% respectively. Complications included incisional hernia (n = 1), and bowel obstruction (n = 1). One patient died of acute myocardial infarction on the third postoperative day. In the ASGB group, median follow-up time was 19.7 months (range: 18-26). At 18 months postoperation BW, BMI, % IBW and % EWL values were 86.6 ± 20.6 kg 30.6 ± 6.6 kg/m2 140.6 ± 29.3% and 64 ± 1% respectively. Gastric wall erosion occurred in two patients and the bands had to be removed. These patients underwent VBG 6 months later. Complications encountered in this group were incisional hernia (n = 1), outlet stenosis and reflux esophagitis (n = 1), reservoir leakage (n = 1) and gastrointestinal bleeding (n = 1). Two patients died of pulmonary embolism and acute gastrointestinal bleeding. Conclusions: Weight reduction was not statistically significant between the two groups. ASGB was easier to perform and less invasive than VBG.     

Clinical and epidemiologic evaluation of pressure ulcers in patients at a university hospital in Turkey.

OBJECTIVE: We sought to measure the incidence of pressure ulcer development at a university health center in Turkey, and to determine whether the Waterlow Pressure Sore Risk (PSR) Scale score predicted pressure ulcer development, stage, or number of ulcers. DESIGN: We prospectively evaluated patients who were hospitalized at our university-based medical center. SETTING AND SUBJECTS: We analyzed data from 22,834 patients hospitalized at the Baskent University Adana Teaching and Medical Research Center in Ankara, Turkey from January 1, 2004 to December 31, 2004, including 360 patients who developed pressure ulcers. INSTRUMENTS: The Waterlow PSR Scale was used to assess pressure ulcer risk. In addition, age, sex, the ward or unit in which the patient was hospitalized, reason for hospitalization, and location and stage of ulcers were collected on a data form designed specifically for this study. METHODS: A single nurse physiotherapist assessed all patients daily during their hospitalization. When a pressure ulcer was diagnosed by the nurse physiotherapist, a physician staged the pressure ulcers based on the US National Pressure Ulcer Advisory Panel (NPUAP) staging system. RESULTS: Three hundred sixty out of 22,834 patients developed 1 or more pressure ulcers, resulting in an incidence rate of 1.6%. Most ulcers (59.2%) occurred in patients hospitalized in the intensive care unit (n = 213). A positive correlation between the Waterlow PSR Scale score and number of ulcers per patient (r: 0.178, P < .01) was identified. No significant correlation was found linking Waterlow PSR Scale score and ulcer stage or the development of a single ulcer. CONCLUSION: We found significantly lower pressure ulcer incidence rates than those commonly reported in the literature, which we believe is principally attributable to short hospital stays and a strong emphasis on preventive nursing care. While high Waterlow PSR scale Scores correlated positively with development of multiple ulcers, this did not predict ulcer stage or the presence of a single pressure ulcer.     

Reconstruction of the wrist pseudoarthrosis due to radioulnar fractures with vascularized fibular graft in a child with neurofibromatosis

Nonunion in the forearm following a radioulnar fracture is one of the nightmares of the orthopedic surgeon. Fortunately, it is rare. We treated a large bone defect of the forearm, using a vascularized fibular graft after excision of the unhealed bone segment in a 10-year-old boy with neurofibromatosis. This situation followed a double fracture that had been operated on several times using conventional methods. Following the debridement of the unhealthy tissues in the pseudoarthrotic region, the vascularized fibula was placed on the dorsal surface of the proximal radius fragment. The distal fragment of the radius was inserted into the fibular cavity and fixation was established with a Kirschner wire distally and with a plate proximally. Only two screws were used to fix the plate. The peroneal artery was anastomosed with the radial artery; one of its venae comitantes was anastomosed with the cephalic vein in an end-to-end fashion. After surgery, the elbow was immobilized at 90 degrees of flexion with a splint for 6 weeks. One year after surgery, forearm stabilization and elbow and hand functions were very satisfactory. However, because the distal epiphyses of the bones were destroyed following the repeated surgery and the original trauma itself, a very prominent difference between the two forearms occurred, suggesting the need for bone lengthening in the future. By presenting this case we would like to conclude that one can expect good bone healing with a vascularized bone transfer in these cases when there is not enough space to place screws, but support can be provided by an external splint and K wire.     

Vascular Endothelial Growth Factor Expression and Cyclosporine Toxicity in Renal Allograft Rejection

The aim of this study was to evaluate the influence of vascular endothelial growth factor (VEGF) on renal function and on development of interstitial fibrosis (IF) in renal allografts. Tubular and interstitial expressions of VEGF and TNF-α, and density of macrophages in the interstitium were examined in 92 patients with nonrejected kidneys, acute rejection (AR), chronic allograft nephropathy (CAN), borderline changes (BC) and acute cyclosporin A (CsA) toxicity. Follow-up biopsy specimens from patients with AR and BC were evaluated for development of IF. A significant difference in tubular and interstitial VEGF expressions was found between patients with AR, BC, CAN and CsA toxicity (p < 0.001). Macrophage infiltration was positively correlated with VEGF and TNF-α expressions (p < 0.001). VEGF expression increased with increasing expression of TNF-α (p < 0.001). Renal function in first 6 months after initial biopsy was better in patients with marked tubular VEGF expression (p < 0.01); however, in follow-up, development of IF and graft loss was found earlier in these patients (p < 0.01 and p < 0.05, respectively). Increased renal VEGF expression has protective properties immediately following renal allograft but allows for increased risk of early IF, and therefore poor graft outcome in the long term.