The pathways for the entry of horseradish peroxidase (HRP) into bile have been investigated using the isolated perfused rat liver operating under one-pass conditions. Following a 1 min one-pass infusion of HRP, two peaks of HRP activity were noted in the bile. The first, at 5-7 min post-infusion, correlated with the biliary secretion of the [3H]methoxyinulin which was infused simultaneously with the HRP. The second peak of HRP activity occurred at 20-25 min, and correlated with the biliary secretion of 125I-IgA, which was also infused simultaneously with the HRP. If the isolated livers were perfused with a medium containing 2.5 microM-colchicine, the biliary secretion of IgA and the second secretion peak of HRP were inhibited by 60%. If rats were pretreated for 12h with alpha-naphthylisothiocyanate (25mg/100g body wt.) prior to liver isolation, the biliary secretion of [3H]methoxyinulin and the first secretion peak of HRP were increased. Taken together, these results suggest that HRP enters the bile via two routes. The faster route, which was increased by alpha-naphthylisothiocyanate and correlated with [3H]methoxyinulin entry into bile, was probably paracellular, involving diffusion across tight junctions. The slower route, which was inhibited by colchicine and correlated with the secretion of IgA, was probably due to transcytosis, possibly within IgA and other transport vesicles.

Background:Diabetes mellitus represents a syndrome complex in which multiple organ systems, including the central nervous system, are affected.Aim:The study was conducted to determine the changes in the brainstem auditory evoked potentials in type 2 diabetes mellitus.Materials and Methods:A cross sectional study was conducted on 126 diabetic males, aged 35-50 years, and 106 age-matched, healthy male volunteers. Brainstem auditory evoked potentials were recorded and the results were analyzed statistically using student's unpaired t-test. The data consisted of wave latencies I, II, III, IV, V and interpeak latencies I-III, III-V and I-V, separately for both ears.Results:The latency of wave IV was significantly delayed only in the right ear, while the latency of waves III, V and interpeak latencies III-V, I-V showed a significant delay bilaterally in diabetic males. However, no significant difference was found between diabetic and control subjects as regards to the latency of wave IV unilaterally in the left ear and the latencies of waves I, II and interpeak latency I-III bilaterally.Conclusion:Diabetes patients have an early involvement of central auditory pathway, which can be detected with fair accuracy with auditory evoked potential studies.

The induction of renal fatty-acid-oxidising enzymes has been investigated following short-term exposure to a group of structurally diverse peroxisome proliferators and compared to the more extensively documented hepatic responses in the rat. There was a marked compound dependence on induction of both cytochrome P-450-IVA1-dependent w-hydroxylation of lauric acid and enzymes of the peroxisomal fatty acid B-oxidation pathway (measured as cyanide-insensitive palmitoyl-CoA oxidation and enoyl-CoA hydratase).Cytochrome P-450 IVAl (or a very closely related isoenzyme in the same gene family) was a major constitutive haemoprotein in rat kidney microsomes and actively supported the o-hydroxylation of lauric acid. This activity was induced 2 -%fold by peroxisome proliferators such as clofibrate, di-(2-ethylhexyl)phthalate, bezafibrate and nafenopin. By using a cDNA probe to the cytochrome P-450 IVAl gene in Northern blot analysis, we have shown that increased renal and hepatic w-hydroxylation of lauric acid, after treatment with peroxisome proliferators is a consequences of a substantial increase in the mRNA coding for this haemoprotein. In addition, programming of an in vitro rabbit reticulocyte translation system with both renal and hepatic RNA resulted in the synthesis of similar (if not identical) cytochrome-P-450-IVAl-related polypeptides. Furthermore, we have provided Western blot evidence that both rat liver and kidney microsomes contain two closely related cytochrome P-450 lVAl polypeptides, the major one characterised by a monomeric molecular mass of 51.5 kDa (identical to authentic, purified hepatic cytochrome P-450 IVA1) and a minor one of 52 kDa. The kidney-supported fatty acid w-hydroxylase activity was refractory to inhibition by a polyclonal antibody to liver cytochrome P -450 IVAl , which may be related to the existence of two closely related (but immunochemically distinct) fatty acid hydroxylases in this tissue.Our studies have also demonstrated that certain of the compounds tested (including clofibrate, bezafibrate and nafenopin) induced renal fatty acid j-oxidation, mirroring the increased w-hydroxylase activity in the endoplasmic reticulum. Our studies have also indicated that the kidney was more refractory to induction of the endoplasmic reticulum and peroxisomal fatty-acid-oxidising enzymes than the liver. Taken collectively, our data is strongly suggestive of a possible linkage of the renal fatty acid oxidative enzymes in these two organelles, a situation that also occurs in the liver. In addition, our studies have provided a possible conceptual framework that may rationalise the decreased susceptibility of the kidney to the toxicity of peroxisome proliferators.The effects of hypolipidaemic agents on rat liver have been extensively studied both in terms of the endoplasmic reticulum changes [l -61 and the associated morphometric and biochemical responses in peroxisomes [7 -91. A recent study has postulated that these adaptive responses are based on a mechanistic interrelationship, whereby chemical c...

No abstract

No abstract