Endoscopic and surgical treatment of non-neoplastic proximal duodenal ulceration in dogs, and anatomical study of proximal duodenal vascularisation.

OBJECTIVES: Proximal duodenal ulceration is often characterised by continuous bleeding, and treatment is challenging. The aims of this study were to investigate the role of vascularisation in proximal duodenal ulceration and describe clinical aspects, endoscopic features and treatment in dogs. MATERIAL AND METHODS: Polyurethane foam casts of gastroduodenal vessels were obtained from five dogs which had died from disorders unrelated to the digestive system. In addition, 12 dogs having proximal duodenal ulcers diagnosed by endoscopic examination were enrolled in a treatment trial. After the endoscopic diagnosis of a duodenal ulcer, all the dogs were treated medically and, in the absence of resolution, were subsequently treated by endoscopic electrocauterisation or by surgery. RESULTS: A submucosal vascular network was evident in all the casts, with a prominent venous plexus seen exclusively in the first half inch of the duodenum. In clinical cases, on endoscopic examination, the duodenal ulcer was located at the proximal part of the duodenum, involving the mesenteric portion of the wall. The dogs not responding to medical treatment (6/12) were treated with endoscopic electrocauterisation, surgical coagulation or resection of the proximal duodenal portion. All the dogs survived until discharge, and the median survival time following discharge was 107.5 days. CLINICAL SIGNIFICANCE: Based on the anatomical details highlighted in this study, the continuous bleeding observed in our patients may have been due to the prominent venous plexus evidenced at the level of the proximal duodenum. Surgical and endoscopic treatments in six patients resolved the ulcer bleeding with no recurrences noted during follow-up.

Anal paracoccidioidomycosis: an unusual presentation of disseminated disease.

We report a patient with an unusual anal ulceration. The biopsy of an anal lesion and subsequent studies revealed a disseminated form of paracoccidioidomycosis, observed in the lungs, small and large bowel. The anorectal disease frequently represents a secondary site of disease, and the patient must be better evaluated.

The effect of ferric iron complex on isolated rat liver mitochondria. I. Respiratory and electrochemical responses.

Addition of iron(III)-gluconate complex to isolated rat liver mitochondria resulted in an increased iron content of mitochondria. Iron was accumulated through a relatively fast process (maximal uptake in less than 2 min incubation) by an energy-independent mechanism. The in vitro iron overload of mitochondria was associated with enhancement in the oxygen consumption, which was due to the induction of lipoperoxidative processes catalyzed by iron. It was found that a concentration of iron as low as 0.1 mM elicits a consistent production of malondialdehyde in mitochondria. Concomitant with the induction of lipoperoxidation a progressive fall in the mitochondrial membrane potential was observed. The occurrence of energy-consuming processes as a consequence of iron addition, and particularly the enhancement of endogenous Ca2+ cycling across the membrane, was suggested as the cause of the membrane potential drop.

The effect of ferric iron complex on isolated rat liver mitochondria. II. Ion movements.

It has been found that addition of iron(III)-gluconate complex to rat liver mitochondria disturbed the mitochondrial Ca2+ transport. Indirect evidence when the changes in the membrane potential during the transport of Ca2+ were followed, as well as direct evidence, when the fluxes of Ca2+ were monitored by a Ca2+-selective electrode, indicated that this iron complex induced an efflux of Ca2+ from liver mitochondria. The mechanisms by which iron induced Ca2+ release appeared to be linked to the induction of lipoperoxidation of mitochondrial membrane. The mitochondrial membrane, however, did not become irreversibly damaged under these conditions, as indicated by its complete repolarization. It was also shown that the induction by iron of lipoperoxidation brought about an efflux of K+ from mitochondria.

The role of pentachlorophenol in causing mitochondrial derangement in hexachlorobenzene induced experimental porphyria.

Hexachlorobenzene feeding to rats for 60 days to induce experimental porphyria resulted in partial and constant uncoupling of oxidative phosphorylation of liver mitochondria from the early phase (i.e. 20 days) of treatment. Direct experimental evidence has been presented that this uncoupling is completely due to the action of pentachlorophenol endogenously formed by metabolism of hexachlorobenzene. The complete restoration of membrane potential by albumin under these conditions indicates that no irreversible damage occurs in the mitochondrial membrane. No appreciable correlation between concentrations of pentachlorophenol and the degree of porphyria has been observed.

Transmembrane potential of liver mitochondria from hexachlorobenzene-and iron-treated rats.

The respiratory parameters and the membrane potential of liver mitochondria from rats treated with either hexachlorobenzene, iron or hexachlorobenzene plus iron, to induce experimental porphyria, have been studied. Partial uncoupling of oxidative phosphorylation has been observed in mitochondria from hexachlorobenzene- and hexachlorobenzene plus iron-treated rats. Direct evidence has been presented that this uncoupling is due to the action of pentachlorophenol endogenously formed by metabolism of hexachlorobenzene. No irreversible damage of mitochondria membrane has been revealed under both these conditions. Normal oxidative phosphorylation has been found in mitochondria from rats treated with iron alone. In contrast, they presented an anomalous membrane potential, fully restored by oligomycin. A possible involvement of lipid peroxidation process, induced by iron, in causing these abnormalities has been suggested.

An investigation on the effect of oligomycin on state-4 respiration in isolated rat-liver mitochondria.

The inhibitory action of oligomycin on State-4 respiration in rat-liver mitochondria has been investigated in detail with regard to the extent, mode and characteristics of the inhibition. The possibility that this effect may be due either to some damage of the mitochondrial preparation used or to the presence of heavy contaminations by microsomes has been excluded. It has been found that the concentration of specific binding sites is the same in State 4 as in State 3. The extent of the inhibition appears to be related to the ADP concentration, rather than to ATP/ADP ratios. The inhibition of this antibiotic on State-4 respiration does not depend on the experimental conditions used (i.e., choice of substrates or composition of the reaction medium). In agreement with these observations, it has been found that the membrane potential of State 4 is significantly increased when oligomycin is added. All these results provide further evidence to the conclusion that a large portion of State-4 respiration is linked to phosphorylation.

Functional efficiency of mitochondrial membrane of rats with hepatic chronic iron overload.

The effect of in vivo hepatic iron overload, induced by two different amounts of iron, on the energy-transducing efficiency of the mitochondrial membrane has been examined. It has been found that when the epatic iron concentration is up to a threshold value mitochondria present an anomalous membrane potential. Addition of oligomycin fully restitutes it. A low content of intramitochondrial K+ is connected with this pathological condition. A relative lack of antioxidant capability is parallely exhibited by these mitochondria. A possible involvement of lipid peroxidation process in vivo in causing the membrane potential drop and the net efflux of intramitochondrial K+ is suggested.

Structural and functional properties of rat liver mitochondria in hexachlorobenzene induced experimental porphyria.

A possible link between changes in iron and porphyrin content in liver mitochondria, from rats treated with either hexachlorobenzene, iron, or hexachlorobenzene plus iron, as a function of treatment time and their structural-functional properties, has been investigated. Normal oxidative phosphorylation in mitochondria from rats treated with iron has been shown. By contrast a significant and constant uncoupling of the phosphorylative process, fully reversed by albumin, in mitochondria from rats treated with hexachlorobenzene and hexachlorobenzene plus iron has been presented. A possible involvement of pentachlorophenol in causing these abnormalities has been proposed.

The effect of oligomycin on rat liver mitochondria respiring in state 4.

It has been found that oligomycin inhibits up to at least 50% state-4 mitochondrial respiration. A time dependence of oligomycin inhibition has been shown. A titration curve for state-4 respiration of sigmoidal profile has been presented. The possibility of misreading this oligomycin effect, so far never reported, has been excluded by evaluating the quality of mitochondrial preparations used in respect to their morphological, functional and electrochemical properties. The conclusion has therefore been put forward that the most part of respiration in steady-state-4 is driven by ATP synthesis.

Phosphorylating efficiency of isolated rat liver mitochondria respiring under the conditions of steady-State 4.

A limited, but significant net formation of ATP was observed during the very first period of respiratory State 4. The synthesis appeared to depend on respiration, since it was completely inhibited by KCN or by 2,4-dinitrophenol. Accordingly, State 4 respiration was observed to be inhibited to a large extent by oligomycin. After the initial increase, the level of ATP remained unmodified under the conditions of steady-state 4. Also, the maintenance of the equilibrium level of ATP was very sensitive to KCN or 2,4-dinitrophenol. Under the very same conditions of State 4, the mitochondria exhibited a significant ATPase activity, which appeared to be competitively inhibited by ADP. Therefore, it might be concluded that the apparently constant level of ATP observed in State 4 results from a balanced equilibrium between a respiration-dependent synthesis and a continuous hydrolysis. A comparison between the amount of ATP hydrolysed in State 4 and the amount of oxygen consumed under the same conditions indicated that the phosphorylating efficiency of respiring mitochondria in State 4 is as high as in State 3.

The role of Mg2+ in the regulation of the structural and functional steady-states in rat liver mitochondria.

A possible relationship between mitochondrial Mg2+ levels, structural configurations, and functional steady states has been studied in rat liver mitochondria. The results show that the concentration of mitochondrial Mg2+ in respiratory state 4 is definitely higher than in respiratory state 3. The metabolic transition from state 3 to state 4 and vice-versa is associated with reversible influx-efflux of about 10 nmol of Mg2+ per mg protein. The net uptake of this aliquot of Mg2+ is a necessary condition in order for the metabolic transition to state 4, both structurally and functionally, to occur. This process requires a threshold concentration of external Mg2+ greater than 5 mM. The phosphorylative mechanism does not appear to depend on the presence or absence of external Mg2+. The role of Mg2+ on the attainment and maintenance of the structural and functional steady state 4 seems to be correlated with its regulatory effect on the concentration of the mitochondrial P(i).

The relation between structural and metabolic steady-states in isolated rat liver mitochondria. A study of the functional significance.

The possible functional significance of the close relation between structural and metabolic steady-states of isolated rat liver mitochondria, has been investigated by analysing the metabolic consequences of a primary block of the structural modifications. The structural changes have been blocked by means of factors acting primarily on the structure and the block was evaluated by electron microscope and angular light scattering measurements. Evidence has been obtained that: (a) the phosphorylative capacity of isolated mitochondria is not modified by conditions that completely abolish the structural changes; therefore, the configurational changes do not constitute as such a mechano-chemical mechanism for energy conservation and transformation. (b) The block of the structural changes is closely associated with the impairment of respiratory control: in fact there appears to be a close relation between the capacity of mitochondria to vary their structure and the ability to vary the respiratory rate, both being a function of ADP concentration.