Factors Influencing Gel-strengthening at the Mucoadhesive-mucus Interface

Abstract— Mechanical spectroscopy was used to examine some of the factors that may affect mucus gel strengthening: the effect of adding various concentrations of sodium chloride; mucoadhesive polymer molecular weight and its concentration; and the introduction of anionic, cationic and neutral polymers. A reduction in the storage modulus of the mucus/mucoadhesive mixture was observed with the introduction of sodium chloride. A poly(acrylic acid) with a molecular weight of 750 kDa gave the optimum mucus gel strengthening effect relative to other molecular weights. An anionic polymer was found to strengthen the mucus gel much more than a neutral or cationic polymer. It was proposed that the gel strengthening effect could be due to the formation of hydrogen bonded intermolecular complexes between the mucoadhesive and the mucus molecules. Furthermore, the complex formed is influenced by the ionic strength of the environment, and the molecular weight, nature and concentration of the mucoadhesive. In all cases the changes in the rheological properties of the mixes could be correlated directly to the strength of mucoadhesion reported in previous studies.     

Obesity and risk of colorectal cancer: a meta-analysis of 31 studies with 70,000 events.

BACKGROUND: Colorectal cancer is the second most common cause of death and illness in developed countries. Previous reviews have suggested that obesity may be associated with 30% to 60% greater risk of colorectal cancer, but little consideration was given to the possible effect of publication bias on the reported association. METHODS: Relevant studies were identified through EMBASE and MEDLINE. Studies were included if they had published quantitative estimates of the association between general obesity [defined here as body mass index (BMI) > or = 30 kg/m(2)] and central obesity (measured using waist circumference) and colorectal cancer. Random-effects meta-analyses were done, involving 70,000 cases of incident colorectal cancer from 31 studies, of which 23 were cohort studies and 8 were case-control studies. RESULTS: After pooling and correcting for publication bias, the estimated relative risk of colorectal cancer was 1.19 [95% confidence interval (95% CI), 1.11-1.29], comparing obese (BMI > or = 30 kg/m(2)) with normal weight (BMI <25 kg/m(2)) people; and 1.45 (95% CI, 1.31-1.61), comparing those with the highest, to the lowest, level of central obesity. After correcting for publication bias, the risk of colorectal cancer was 1.41 (95% CI, 1.30-1.54) in men compared with 1.08 (95% CI, 0.98-1.18) for women (P(heterogeneity) <0.001). There was evidence of a dose-response relationship between BMI and colorectal cancer: for a 2 kg/m(2) increase in BMI, the risk of colorectal cancer increased by 7% (4-10%). For a 2-cm increase in waist circumference, the risk increased by 4% (2-5%). CONCLUSIONS: Obesity has a direct and independent relationship with colorectal cancer, although the strength of the association with general obesity is smaller than previously reported.     

Total antioxidant capacity and levels of epidermal growth factor and nitric oxide in blood and saliva of insulin-dependent diabetic patients

BACKGROUND: The aim of this study was to examine how type 1 diabetic patients have altered levels of lipid peroxidation, antioxidant defense, NO and EGF in their plasma and saliva. We tested the differences in lipid peroxidation level, antioxidant power, and concentrations of epidermal growth factor (EGF) and nitric oxide (NO) in saliva and blood of type 1 diabetic subjects in comparison to healthy control subjects. METHODS: Nineteen subjects with type 1 diabetes mellitus and 19 healthy age- and sex-matched control subjects were included in the study. Blood and saliva samples were obtained and analyzed for thiobarbituric reactive substances (TBARS) as a marker of lipid peroxidation, ferric reducing ability (total antioxidant power), EGF and NO levels. RESULTS: TBARS levels did not show a significant difference between the two groups. Analysis of antioxidant power revealed that saliva and plasma of diabetic patients had more antioxidant power (p <0.01) than the healthy control population (107 +/- 10.35 vs. 11.14 +/- 4.66 and 192 +/- 12.3 vs. 142 +/- 15.2 mmol/L, respectively). Concentration of EGF was increased (p <0.01) in saliva whereas it was reduced (p <0.01) in plasma of diabetic patients in comparison to those of healthy subjects (2423 +/- 322 vs. 1513 +/- 341 and 125 +/- 14 vs. 346 +/- 60 pg/mL, respectively). NO level increased in both saliva and plasma of diabetic patients in comparison to those of healthy subjects (46.61 +/- 7 vs. 72.89 +/- 13 and 62.11 +/- 4.6 vs. 76.25 +/- 5 micromol/L, respectively). Blood HbA1c (%) of patients was significantly higher than that of controls (8.3 +/- 0.32 vs. 5.4 +/- 0.24, p <0.01). CONCLUSIONS: Existence of increased total antioxidant power in the presence of normal lipid peroxidation in plasma and saliva of type 1 diabetic patients indicates the existence of oxidative stress. Increased salivary EGF and NO levels in association with elevated TAOP is interesting and should be further studied.     

Potassium-titanyl-phosphate laser laparoscopic partial nephrectomy without hilar clamping in the survival calf model

PURPOSE: Laparoscopic partial nephrectomy (LPN) with hilar clamping represents the various challenges associated with warm ischemia. We tested the feasibility, and acute and chronic outcomes of LPN using a potassium-titanyl-phosphate (KTP) laser without vascular hilar clamping in the survival calf model. MATERIALS AND METHODS: Six Jersey calves weighing 76 to 94 kg underwent a total of 12 staged bilateral transperitoneal laser LPNs of the mid/lower pole using an 80 W KTP laser, including left kidney chronic LPN with 1-month followup in 6 and right kidney acute LPN with immediate sacrifice in 6. Two techniques (ablative vaporization in 5 subjects and wedge resection in 7) were evaluated. Renal parenchymal resection and hemostasis were achieved only with the laser without any adjunctive hemostatic sutures or bioadhesives. Retrograde pyelography, renal arteriography and histological analyses were performed. RESULTS: All 12 procedures were successful performed laparoscopically without open conversion and 11 (92%) were done without hilar clamping. Mean total operative time was 2.9 hours (range 1.5 to 5) and mean blood loss was 119 cc (range 25 to 300). Mean lasing time was 56 minutes (range 20 to 100) with an average energy use of 54 kJ. Mean preoperative and postoperative hemoglobin (10.38 and 10.52 gm/dl) and serum creatinine (0.46 and 0.4 gm/dl, respectively) were similar. At 1-month followup there was no evidence of urinary leakage or arteriovenous fistula. CONCLUSIONS: This initial study of laparoscopic KTP laser partial nephrectomy without hilar clamping confirms its technical feasibility in most cases and good short-term outcomes. This success of laser LPN in the robust survival calf model with its human-sized kidney holds promise for future clinical application.