Reduction using an immunomodulator of the level of respiratory infections in chronic bronchitis

Fifty-six patients with recurrent bronchopulmonary infections associated with chronic bronchitis were randomly allocated to 2 groups, to assess whether treatment with an immunomodulator, Diribiotin CK, could enhance resistance to infection. The double-blind, placebo-controlled prospective trial over a 9 month period showed that this immunomodulator was well tolerated and significantly reduced the rate of respiratory tract infection. The drug also significantly reduced the prescribing of antibiotic medication and the rate of absenteism from work. These effects have been demonstrated in a rigorously designed clinical study. This is the first time that a clear clinical activity has been attributed to an inducer of soluble mediators of immunity.     

In vivo demonstration of the absorptive function of the middle ear epithelium

The present study investigated in vivo fluid and ion transport across the middle ear epithelium. The tympanic membrane of rats was punctured under general anesthesia. A capillary tube was fitted to the external auditory canal and the bulla filled with various solutions. Middle ear (ME) fluid volume variations were then measured at constant pressure.

When saline was used, a linear decrease of fluid volume was apparent. Replacement of sodium with a non-permeable cation (N-methyl-d-glucamin) reduced the absorption rate from 0.065 ± 0.008 to 0.019 ± 0.003 μl/min (P < 0.05, n = 6). Similarly, amiloride (10⁻³ M), a sodium channel antagonist, reduced the absorption rate to 0.027 ± 0.006 μl/min (P < 0.05, n = 6). Net absorption was abolished when chloride was substituted with gluconate: −0.008 ± 0.004 μl/min (P < 0.02, n = 6), which might have been related (i) to the role of chloride as a diffusible anion through the paracellular pathway, or (ii) to the secretion of chloride through apical channels. However in this condition, 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid, a chloride channel blocker, did not affect the rate of fluid exchange −0.008 ± 0.007 μl/min (P = 0.75, n = 6).

This model provides the first in vivo evidence for the absorptive function of the ME. Fluid introduced into the ME cavity disappears due to active transport through the mucosa. This process is sodium-dependent and can be hindered by high concentration of amiloride. The rate of absorption is high enough to allow total clearance of fluid from the cavity of the middle ear within 13 h. This process might play a role in the maintaining a fluid-free and gas-filled middle ear cavity.     

Active life expectancy: factors influencing regional and gender differences]

Active life expectancy (ALE) is defined as an expected duration to be spent with a certain level of physical/mental function. The objectives of this article are to indicate ALE values based on our prospective observation, and to discuss factors influencing regional and gender differences in ALE values. We estimated ALE without disability in basic activities of daily living (ADL) on a 5% random sample (n = 3,459) of the residents aged 65 years and over in Sendai City between 1988 and 1991. At the age 65, ALE was 14.7 years for men and 17.7 years for women. ALE occupied 91% of the total life expectancy for men and 87% for women. As compared with the reports for the American elderly, ALE was longer in Sendai than in the United States. The duration to be spent with disability was shorter among the subjects in Sendai. We estimated ALEs in three functional areas: basic ADL, instrumental ADL, and mobility, on all the residents aged 65 years and over (n = 3,590) at Wakuya Town between 1994 and 1996. For both sexes, ALE in IADL was shorter than those in basic ADL and mobility. The development and progression of disability were different between sexes: men experienced disability at a younger age and progressed at a faster rate than women.     

Defective N-sulfation of heparan sulfate proteoglycans limits PDGF-BB binding and pericyte recruitment in vascular development

During vascular development, endothelial platelet-derived growth factor B (PDGF-B) is critical for pericyte recruitment. Deletion of the conserved C-terminal heparin-binding motif impairs PDGF-BB retention and pericyte recruitment in vivo, suggesting a potential role for heparan sulfate (HS) in PDGF-BB function during vascular development. We studied the participation of HS chains in pericyte recruitment using two mouse models with altered HS biosynthesis. Reduction of N-sulfation due to deficiency in N-deacetylase/N-sulfotransferase-1 attenuated PDGF-BB binding in vitro, and led to pericyte detachment and delayed pericyte migration in vivo. Reduced N-sulfation also impaired PDGF-BB signaling and directed cell migration, but not proliferation. In contrast, HS from glucuronyl C5-epimerase mutants, which is extensively N- and 6-O-sulfated, but lacks 2-O-sulfated L-iduronic acid residues, retained PDGF-BB in vitro, and pericyte recruitment in vivo was only transiently delayed. These observations were supported by in vitro characterization of the structural features in HS important for PDGF-BB binding. We conclude that pericyte recruitment requires HS with sufficiently extended and appropriately spaced N-sulfated domains to retain PDGF-BB and activate PDGF receptor beta (PDGFRbeta) signaling, whereas the detailed sequence of monosaccharide and sulfate residues does not appear to be important for this interaction.