A comparison of the insulinotropic and the insulin-inhibitory actions of gut peptides on newborn and adult rat islet cells

The objective of this study was to examine the release of insulin from cultured islet cells, taken from the pancreas of newborn and adult rats, in response to gastric inhibitory polypeptide (GIP), cholecystokinin-8 (CCK-8), calcitonin gene-related peptide (CGRP), and pancreastatin. GIP (10(-9)-10(-7) M) potentiated glucose-stimulated release of insulin in a dose-dependent fashion from both newborn and adult islet cells. CCK-8 (greater than 10(-8) M) also increased glucose-stimulated release of insulin from newborn islet cells, however its effect was not significant and not as strong as that observed with adult islet cells. Culture of newborn islet cells for 3 weeks with media containing high concentrations of glucose (16.7 mM) enhanced insulin release in response to CCK-8. CGRP did not affect the release of insulin from newborn islet cells, whereas at 10(-10) M, it reduced the release of insulin from adult islet cells by 66 +/- 4%. Pancreastatin (10(-9)-10(-8) M) did not affect the release of insulin from newborn islet cells when cells were incubated with 4.2 mM glucose, whereas it stimulated the release of insulin from adult islet cells in a dose-dependent fashion. When incubated with 16.7 mM glucose, pancreastatin inhibited the release of insulin from both newborn and adult islet cells. These results indicate that newborn islet cells experience developmental changes which render them responsive to enteric peptides.     

Albumin adsorption on alkyl chain derivatized polyurethanes. II. The effect of alkyl chain length

Linear alkyl chains containing 2, 10 and 18 carbon atoms were grafted to 10% of the urethane nitrogens in a polyether-polyurethane. The polyurethane was synthesized from methylene bis(p-phenyl isocyanate), 1,4-butanediol, and polytetramethylene oxide of 1000 molecular weight in a molar ratio of 3/2/1. Fourier transform infrared spectroscopy and attenuated total reflectance optics were used to study the adsorption of 5.0 mg/ml human serum albumin (HSA) at 37 degrees C to the derivatized and non-derivatized polymers. Both delipidized HSA and HSA containing 6.5 mol stearic acid per mol of albumin were used to study the effect of chain length upon the initial adsorption rate, the total amount adsorbed in 1 h, and the desorption rate. The initial adsorption rates revealed that non-specific adsorption was similar upon all four polymers. An increase in initial adsorption rate upon the C-18 derivatized polymer was attributed to a specific binding interaction between the HSA and the grafted alkyl chains. The conformational stability of the HSA also affected the adsorption rate. The total amount adsorbed after 1 h decreased as the alkyl chain length increased from 2 to 18 methylene groups. The desorption rate decreased in magnitude as the alkyl chain length increased from C-2 to C-18. These results support a hypothesis that alkyl chain length influences the interaction between albumin and an alkylated polymer system.     

The association between water fluoridation and hip fracture among white women and men aged 65 years and older. A national ecologic study.

For the past 45 years, there has been a great deal of debate regarding the health issues surrounding the fluoridation of public water supplies. In order to assess the association between fluoridation and hip fracture, we identified 129 counties across the United States considered to be exposed to public water fluoridation and 194 counties without exposure. Data from the Health Care Financing Administration and the Department of Veterans Affairs were used to calculate the incidence of hip fracture among white persons, aged 65 years or older, in fluoridated and nonfluoridated counties. There was a small statistically significant positive association between fracture rates and fluoridation. The relative risk (95% confidence interval) of fracture in fluoridated counties compared to nonfluoridated counties was 1.08 (1.06 to 1.10) for women and 1.17 (1.13 to 1.22) for men. As comparisons were made at the grouped level, it may be inappropriate at this time to draw inferences at the individual level. The relationship observed at the county level needs to be duplicated at the individual level with more precise measures of fluoride exposure.     

Fibrosarcomatous change in dermatofibrosarcoma protuberans

This report describes six patients with dermatofibrosarcoma protuberans (DFSP) that contained fibrosarcomatous areas (FS). The clinical signs and symptoms, ages of the patients, and anatomic distribution of the tumors were similar to those of uncomplicated DFSP. FS was concentrated in the subcutis in each case and comprised more than 50% of the tumor in four cases. The characteristic storiform cellular arrangement of DFSP was replaced by long, gently sweeping fascicles of spindle cells that intersected at various angles, forming the so-called herringbone pattern. Trapped fat cells, characteristic of DFSP when it infiltrates subcutaneous tissue, were absent in five of the six FS and only focally present in one. Two FS were grade 1; their cytologic features were similar to those of DFSP. Four FS were grade 2 and had cytologic atypia exceeding that of DFSP. There was a statistical difference between the mitotic rates of DFSP and FS. Five patients were alive and well at the time of last follow-up (median, 2 years), and one patient had an unexcised recurrence when last examined. Six similar cases from the literature are reviewed; in one of them, the FS metastasized.     

Ct detection of cerebral metastases inapparent on magnetic resonance imaging scan

We report a case of malignant melanoma, metastatic to the brain, in which disease was not detected by magnetic resonance imaging but was detected by contrast enhanced computed tomography. At least in some instances, magnetic resonance imaging fails to detect disease that is apparent by computed tomography.     

Nemaline myopathy of cats

An apparently inherited myopathy, characterized by the presence of large numbers of nemaline rods in skeletal muscle fibers, was investigated in five cats. Onset of signs varied from 6 months to 1.5 years of age and consisted of reluctance to move, jerky gait and muscle twitching, hyporeflexia, and muscle wasting, which was most prominent in the proximal muscles of the forelimbs. All of the cats, three males and two females, were from the same dam. In addition to the presence of rods, the myopathy was characterized by marked fiber size variation, with atrophy of type 1 and type 2a muscle fibers. In addition, there was infolding of the sarcolemma and fiber splitting. Ultrastructurally, the rods closely resembled those described in human nemaline myopathy.     

Safety and effect of transforming growth factor-β2 for treatment of venous stasis ulcers

Transforming growth factor-beta(2) promotes healing in a variety of animal models and exhibits clinical effects thought to be mediated by connective tissue formation. Two clinical trials were conducted to evaluate the safety and effect of transforming growth factor-beta(2) purified from bovine bone and delivered topically to venous stasis ulcers three times per week for up to 6 weeks by means of a lyophilized collagen vehicle. The first was an open-label trial comparing transforming growth factor-beta(2) purified from bovine bone (0.5 microg/cm(2)) with a placebo consisting of lyophilized collagen vehicle-without active drug. After no safety issues arose in that trial, a prospectively randomized, closed-label, observer-blinded, three-armed trial was conducted to compare bovine transforming growth factor-beta(2) (2.5 microg/cm(2)) with the collagen matrix placebo vehicle and with a standard dressing. Standardized elastic compression was applied to all test extremities. The rate of reduction of ulcer area as measured by planimetry was the primary measure of effect. No serious safety-related events occurred in either trial. Clinical evaluation suggested that improvement in the quality and quantity of granulation tissue appeared to precede epithelialization of ulcers treated with bovine transforming growth factor-beta(2). In both studies, treatment with bovine transforming growth factor-beta(2) appeared to have a positive effect on the rate of ulcer closure, whereas ulcers in the control groups continued to exhibit impaired healing. In the open-label study, the mean rate of closure of ulcers treated with bovine transforming growth factor-beta(2) was significantly greater than that of ulcers treated with placebo. There was likewise enhanced reduction in ulcer area in the ulcers treated with bovine transforming growth factor-beta(2) in the second trial. However, because of a higher variability in patient response and a greater placebo effect, the difference was not significant. The placebo was not worse than the standard care arm, thereby showing that the vehicle is not injurious to healing. The combined results of the two trials suggest that, at doses of 0.5 to 2.5 microg/cm(2), bovine transforming growth factor-beta(2) is safe as a topically applied agent in a collagen matrix vehicle and can have a positive effect on closure of venous stasis ulcers. Large multicenter trials appear to be indicated to evaluate fully the potential utility of transforming growth factor-beta(2) in accelerating closure of chronic dermal ulcers.