Novel diffusion cell for in vitro transdermal permeation, compatible with automated dynamic sampling

The development of a new diffusion cell for in vitro transdermal permeation is described. The so-called Kelder cells were used in combination with the ASPEC system (Automatic Sample Preparation with Extraction Columns), which is designed for the automation of solid-extractions (SPE). Instead of SPE columns, 20 Kelder cells were placed in the racks. This allowed automatic sampling of up to 20 cells for 24 h in a dynamic mode. The cells consist of an inlet compartment, a donor compartment and a receptor compartment. The size and the depth of the inlet compartment were important to avoid entrapment of air bubbles in the receptor compartment. The Kelder cells mimic blood flow beneath the skin by replacement of the permeating drug every 2 min. Hence sink condition are more easily maintained than with the static Franz diffusion cell. The performance of the cells was tested with permeation experiments using atropine as a model drug permeating through an artificial membrane (Silastic). The use of this skin model minimized the variability in permeation of atropine as compared with human skin.     

THERMOLUMINESCENT AUTHENTICATION OF ANCIENT CHINESE POTTERY

A rapid and effective TL technique to authenticate ancient Chinese pottery is proposed in the paper.Twenty three samples,ranging in age from 200to 9000a,including multiple styles and shapes and drawn from diverse and remote areas in China have been used to establish the typical annual dose as 5.5mGy/a and its associated deviation.Ten unauthenticated samples are then appraised using the technique which,in nearly all cases,leads to satisfactory results.     

TIMP-1 contact sites and perturbations of stromelysin 1 mapped by NMR and a paramagnetic surface probe

Surfaces of the 173 residue catalytic domain of human matrix metalloproteinase 3 (MMP-3(DeltaC)) affected by binding of the N-terminal, 126 residue inhibitory domain of human TIMP-1 (N-TIMP-1) have been investigated using an amide-directed, NMR-based approach. The interface was mapped by a novel method that compares amide proton line broadening by paramagnetic Gd-EDTA in the presence and absence of the binding partner. The results are consistent with the X-ray model of the complex of MMP-3(DeltaC) with TIMP-1 (Gomis-Rüth et al. (1997) Nature 389, 77-81). Residues Tyr155, Asn162, Val163, Leu164, His166, Ala167, Ala169, and Phe210 of MMP-3(DeltaC) are protected from broadening by the Gd-EDTA probe by binding to N-TIMP-1. N-TIMP-1-induced exposure of backbone amides of Asp238, Asn240, Gly241, and Ser244 of helix C of MMP-3(DeltaC) to Gd-EDTA confirms that the displacement of the N-terminus of MMP-3(DeltaC) occurs not only in the crystal but also in solution. These results validate comparative paramagnetic surface probing as a means of mapping protein-protein interfaces. Novel N-TIMP-1-dependent changes in hydrogen bonding near the active site of MMP-3(DeltaC) are reported. N-TIMP-1 binding causes the amide of Tyr223 of MMP-3(DeltaC) bound by N-TIMP-1 to exchange with water rapidly, implying a lack of the hydrogen bond observed in the crystal structure. The backbone amide proton of Asn162 becomes protected from rapid exchange upon forming a complex with N-TIMP-1 and could form a hydrogen bond to N-TIMP-1. N-TIMP-1 binding dramatically increases the rate of amide hydrogen exchange of Asp177 of the fifth beta strand of MMP-3(DeltaC), disrupting its otherwise stable hydrogen bond.     

Hepatitis among plasma fractionation workers. An industry-wide study

An industry-wide survey of plasm fractionation facilities in the United States was conducted during 1973-74. Hepatitis was reported among the workers with varying degrees of plasma contact at all plant sites. For each of fourteen facilities in this investigation, field inspections disclosed: (1) numerous overt instances of employee-product contact: (2) inconsistent methodologic approaches at virtually all stages of the plasma fractionation process; (3) at low level of management and employee awareness regarding the potential bio-hazard identified; and (4) disparate examples of hepatitis surveillance and prophylaxis. Our data suggests that there is a high risk of hepatitis among plasma fractionation workers and, as such, much more attention needs to be focused on the reduction of health hazards within this industry.     

Effects of sodium bicarbonate with three ratios of hay crop silage to concentrate for dairy cows

Three ruminally cannulated Holstein cows were fed total mixed diets of hay crop silage and concentrate (30:70, 50:50, 70:30, 100:0) to evaluate effects of sodium bicarbonate supplements equivalent to 0, .4, and .7% of total ration dry matter (0, 68, and 114 g/d). Yields of milk, fat-corrected milk, fat, protein, and solids-not-fat, percentages of milk protein and solids-not-fat, and efficiency of production of fat-corrected milk declined with decreasing concentrate proportion. Buffer supplementation reduced milk fat percentage and milk yield was greater with 68 g/d sodium bicarbonate than with 114 g/d. Digestibilities of dry matter, organic matter, gross energy, cell solubles, and crude protein declined with decreasing proportion of concentrate while cellulose digestibility increased linearly. The proportion of dietary nitrogen transferred to milk decreased linearly with decreasing proportion of concentrate and sodium bicarbonate increased this transfer with the 70% concentrate diet. Sodium bicarbonate increased ruminal pH and acetate proportion while decreasing ammonia concentration. Acetate:propionate ratio was decreased by sodium bicarbonate addition to the 70% concentrate diet. High concentrate diets with hay crop silage may require higher amounts of buffers to influence production.     

Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomized double-blind study

OBJECTIVE: Obesity is an important risk factor for type 2 diabetes. Weight loss in patients with type 2 diabetes is associated with improved glycemic control and reduced cardiovascular disease risk factors, but weight loss is notably difficult to achieve and sustain with caloric restriction and exercise. The purpose of this study was to assess the impact of treatment with orlistat, a pancreatic lipase inhibitor, on weight loss, glycemic control, and serum lipid levels in obese patients with type 2 diabetes on sulfonylurea medications. RESEARCH DESIGN AND METHODS: In a multicenter 57-week randomized double-blind placebo-controlled study, 120 mg orlistat or placebo was administered orally three times a day with a mildly hypocaloric diet to 391 obese men and women with type 2 diabetes who were aged > 18 years, had a BMI of 28-40 kg/m2, and were clinically stable on oral sulfonylureas. Changes in body weight, glycemic control, lipid levels, and drug tolerability were measured. RESULTS: After 1 year of treatment, the orlistat group lost 6.2 +/- 0.45% (mean +/- SEM) of initial body weight vs. 4.3 +/- 0.49% in the placebo group (P < 0.001). Twice as many patients receiving orlistat (49 vs. 23%) lost > or = 5% of initial body weight (P < 0.001). Orlistat treatment plus diet compared with placebo plus diet was associated with significant improvement in glycemic control, as reflected in decreases in HbA1c (P < 0.001) and fasting plasma glucose (P < 0.001) and in dosage reductions of oral sulfonylurea medication (P < 0.01). Orlistat therapy also resulted in significantly greater improvements than placebo in several lipid parameters, namely, greater reductions in total cholesterol, (P < 0.001), LDL cholesterol (P < 0.001), triglycerides (P < 0.05), apolipoprotein B (P < 0.001), and the LDL-to-HDL cholesterol ratio (P < 0.001). Mild to moderate and transient gastrointestinal events were reported with orlistat therapy, although their association with study withdrawal was low. Fat-soluble vitamin levels generally remained within the reference range, and vitamin supplementation was required in only a few patients. CONCLUSIONS: Orlistat is an effective treatment modality in obese patients with type 2 diabetes with respect to clinically meaningful weight loss and maintenance of weight loss, improved glycemic control, and improved lipid profile.     

Circulating soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in patients with gastric cancer

The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 45 patients with gastric cancer before treatment and their correlation with clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology, survival and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with gastric cancer in comparison with the group of healthy subjects (P < 0.00001 and P < 0.0001 respectively). Increased serum concentrations of VCAM-1 were associated with locally advanced and metastatic disease whereas ICAM-1 was significantly elevated both in local and in advanced/metastatic disease. Soluble E-cadherin and E-selectin concentrations did not show any significant elevation in gastric cancer patients. Concentrations of soluble adhesion molecules showed significant correlation with each other (except E-selectin and VCAM-1) and with alkaline phosphatase. Soluble ICAM-1 and VCAM-1 were significantly associated with an elevated total white cell count. Patients with elevated VCAM-1 had significantly poorer survival in comparison with patients with normal serum levels (P = 0.0361).     

Meshlaparostomy--a comparison between polypropylene mesh and indigenous nylon net

Polypropylene mesh, the routinely used material for mesh laparostomies is expensive. A economical and easily available substitute-nylon net was compared with polypropylene mesh with regard to efficacy and wound complications in a retrospective study. 51 patients, 25 in the polypropylene mesh group and 26 in the nylon net group were studied. The groups were matched with respect to age, sex, indication for surgery and mortality. The mean hospital stay (65 vs 54 days), fate of the wound, incidence of mesh extrusion (26% vs 20%), bowel perforation (1 vs none) and incisional hernia formation (21% vs 20%) in those with polypropylene mesh and nylon net respectively was similar. In conclusion, nylon net is an effective and inexpensive indigenous substitute for polypropylene mesh for mesh laparostomies.