In vitro human nail penetration and kinetics of panthenol.

The in vitro absorption of panthenol into and through the human nail was examined in this study. Panthenol, the alcohol form of pantothenic acid (vitamin B5), is believed to act as a humectant and improve the flexibility and strength of nails. A liquid nail treatment formulated with panthenol (2%) was compared to a solution of panthenol (2%) in water. Fingernail specimens were dosed daily for 7 days with either the nail treatment (non-lacquer film forming) formulation or aqueous solution with sampling performed every 24 h. Panthenol concentrations were determined in the dorsal surface, interior (by drilling and removal) and in the supporting bed under the human nail. Panthenol levels in the dorsal nail (R(2) = 0.87; P < 0.001), nail interior (R(2) = 0.94; P < 0.001) and nail supporting bed (R(2) = 0.79; P < 0.003) showed a significant linear increase with each day of dosing. Significantly more panthenol was delivered into the interior nail and supporting bed by a nail treatment formulation than from an aqueous solution. The film acts not only as a reservoir of panthenol, but also acts to increase the hydration of the nail and the thermodynamic activity of panthenol as well, thereby enhancing diffusion.

Long-term zoledronic acid treatment increases bone structure and mechanical strength of long bones of ovariectomized adult rats.

Zoledronic acid (ZOL) is a highly potent heterocyclic bisphosphonate which has been shown to inhibit bone resorption in short-term experiments in young growing animals. In this investigation we have evaluated the effects of a 1-year administration to mature, ovariectomized (OVX) rats as a model for postmenopausal osteoporosis in order to elucidate (1) the temporal changes in urinary biochemical markers of bone turnover and femoral bone mineral density (BMD), (2) to measure changes of static and dynamic histomorphometric parameters and mechanical strength, and (3) to assess the preventive effects of chronic treatment with ZOL on these parameters. In urine, deoxypyridinoline increased after OVX and was significantly reduced by ZOL administration, indicative of a reduced bone collagen turnover. These changes were accompanied by alterations of tibial cancellous bone: trabecular bone volume and parameters of bone architecture were significantly augmented by ZOL and bone formation rates fell as a consequence of suppressed bone turnover, but were still measurable. No signs of "frozen bone" or osteomalacia could be detected. BMD of the whole femurs rose in sham-operated control animals (SHAM) during the entire experimental period, whereas in OVX animals, BMD plateaued after 32 weeks at a lower level. ZOL at a low dose (0.3 mg/kg/week s.c.) did not alter whole femur BMD, but at higher doses (1.5 and 7.5 mg/kg/week s.c.) BMD increased to the level of the SHAM group. A distinct pattern was noted for the distal quarter of the femur, a region rich in cancellous bone: BMD initially increased in all treatment groups except the OVX group, and at a later stage fell again at a comparable rate irrespective of treatment. Mechanical stability, as assessed by a 3-point bending test, was significantly increased by all doses of ZOL and exceeded OVX and sham-operated controls. The effects on mechanical properties were observed at a low dose which did not measurably increase femoral BMD after 1-year treatment. Multiregression analysis revealed a significant positive correlation between maximum load and BMD, and a significant negative correlation of maximum load with labeled perimeter, a marker of bone formation and turnover. No significant correlation was found with urinary deoxypyridinoline, a marker of bone resorption. The data show that mechanical testing detects improvements of functional bone quality following low dose bisphosphonate treatment which are not identified by standard DXA measurements of BMD.

Skeletal changes in the ovariectomised ewe and subsequent response to treatment with 17 beta oestradiol.

The ewe has been suggested as a suitable large animal model for assessment of therapeutic agents for the treatment of osteoporosis. In this study we asses the response of ewe bone mineral parameters, using dual energy x ray absorptiometry (DXA), after ovariectomy. Regular DXA analysis was performed over a period of 75 weeks followed by a period of dosing with 17 beta oestradiol. Total body bone mineral density (BMD) was reduced in ovariectomised animals 15 weeks post operatively. BMD remained lower than control animals for the entire pre dose period. Subsequently, dosing with 17 beta oestradiol prevented further loss of bone over a period of 38 weeks. Several complicating factors were noted during the study including seasonal BMD variation, a correlation between fat/lean ratio and total body BMD together with a reversible reduction in bone mineral content as a result of lactation. Also changes in BMD were associated with age at ovariectomy.

Preliminary data from investigations of the in vivo biopersistence of three experimental glass fibres of varying chemical composition.

The durability of three experimental glass fibres (X7753, X7484, and X7779) was investigated in vivo. These fibres had in vitro dissolution rates of 600, 150, and 2 ng cm-2 hour-1, respectively. Three groups of female Fischer-344 rats were intratracheally instilled with a 1.2 mg suspension of one of each of the fibre types. All fibres had previously been neutron activated, to produce radioactive 24Na within the glass, which served as a radiotracer. At 2 days post instillation (PI) about 1 x 10(6) glass fibres were within the pulmonary region of the lung. Animals were killed at various time points from 2 to 360 days PI. Fibres were recovered from the animal lungs by hypochlorite digestion. The retention and morphometry of these fibres was investigated, and preliminary results are presented. After 360 days in the lung, the number of X7753 and X7484 fibres fell respectively to 10% and 50% of those present at 2 days PI. There was no detectable reduction in the number of X7779 fibres in the lung over this period. Morphometric analyses demonstrated a 53% and 22% reduction in the mean length of the X7753 and X7484 fibres, after 360 days in the lung. Reduction in diameter was apparent after only 28 days for the these fibre types. No change in the mean size of the X7779 fibres was observed during the study. The fibre morphometry data suggested that short fibres dissolved at a slower rate than long fibres. In general the in vivo fibre retention and morphometry data reflected the measured in vitro dissolution rate.

Alveolar macrophage kinetics after inhalation of 239PuO2 by CBA/Ca mice: changes in synthesis of DNA.

For workers in the nuclear industry, the primary route for the entry of radioactive materials into the body is by inhalation, and the rate of clearance of particles from the pulmonary region of the lung is an important factor in determining radiation dose. It is the function of alveolar macrophages (AM) to maintain the sterility of the lung and to remove insoluble particles from the respiratory surfaces and airways. The AM population is not static, and under normal conditions the loss of macrophages from the alveoli via the conducting airways is balanced by renewal. Studies of the effects of external irradiation on the kinetics of AM are numerous, but to date little is known about the effects of inhaled radioactive particles. In this investigation the effects of inhaled 239PuO2 (plutonium dioxide) particles on the synthesis of DNA by AM were studied at times up to 77 days after exposure. We also measured the number of cells recovered by bronchoalveolar lavage and the incidence of AM with nuclear aberrations. The latter provides a sensitive indicator of the effects of radiation. One of the earliest effects observed after exposure to 239PuO2 is a reduction in the number of AM recovered by lavage. This reduction is associated with a 3-fold reduction in the proportion of AM undergoing DNA synthesis at early times after exposure. The overall mean pulse labeling index of AM recovered from sham-exposed mice is 1.68%, and no trend is observed with time.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA synthesis in alveolar macrophages and other changes in lavaged cells following exposure of CBA/H mice to cigarette smoke.

Traditional methods to determine the proportion of cells in S-phase use radiolabeled precursors of DNA, such as 3H-thymidine, which become incorporated into DNA during its synthesis and are visualized either in tissue sections or in cell preparations by autoradiography. At the Harwell Laboratory the effects of inhaled alpha-emitting actinides on the pulmonary alveolar macrophage population of the rodent lung are being studied. For this research the use of an autoradiographic technique to determine the proportion of cells in S-phase is inappropriate, because of the possible presence of competing sources of radioactivity in the cells under investigation. Consequently, an alternative method has been developed. In this method, 5-bromodeoxyuridine (BrdU), an analogue of thymidine, is incorporated into cells undergoing DNA synthesis. Fluorescein-conjugated monoclonal antibodies, highly specific for BrdU substituted DNA, are available commercially and may be used as a probe for BrdU-labeled cells. This technique for identifying cells in S-phase has been described previously for the flow cytometric analysis of cell suspensions and for cells in tissue sections. An adaptation of this technique for use on cytocentrifuge preparations of cells recovered from mouse lung by bronchoalveolar lavage has been developed and its use is described. Some preliminary results of a short-term experiment with CBA/H mice to determine the effects of exposure to cigarette smoke on the DNA synthesis of alveolar macrophages are also included.