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Biomedical subjects

M A Aller

Publications and source records attributed to M A Aller.

At least 19 recordsLinked to original sources

The inflammatory response recapitulates phylogeny through trophic mechanisms to the injured tissue.

The post-traumatic local acute inflammatory response is described as a succession of three functional phases of possible trophic significance: 1. Nervous or immediate (ischemia-reperfusion); 2. Immune or intermediate (infiltration by inflammatory and bacterial cells) and 3. Endocrine or late (angiogenesis with regeneration and/or cicatrization). Each of these phases emphasizes the trophic role of the mechanisms in the damaged tissue. Hence, the nervous phase is predominated by nutrition by diffusion; in the immune phase trophism is mediated by inflammatory cells and bacteria and, finally, in the endocrine phase, the blood circulation and oxidative metabolism play the most significant nutritive role. Since these trophic mechanisms are of increasing complexity, progressing from anoxia to total specialization in the use of oxygen to obtain usable energy, it could be speculated that they represent the successive reappearance of the stages that take place during the evolution of life on Earth, from ancient times without oxygen. In this sense, the inflammatory response could recapitulate phylogeny through the successive expression of pathophysiologic mechanisms that have a trophic meaning to the injured tissue.

Animals↗

Evaluation of two experimental models of hepatic encephalopathy in rats.

The serious neuropsychological repercussions of hepatic encephalopathy have led to the creation of several experimental models in order to better understand the pathogenesis of the disease. In the present investigation, two possible causes of hepatic encephalopathy, cholestasis and portal hypertension, were chosen to study the behavioral impairments caused by the disease using an object recognition task. This working memory test is based on a paradigm of spontaneous delayed non-matching to sample and was performed 60 days after surgery. Male Wistar rats (225-250 g) were divided into three groups: two experimental groups, microsurgical cholestasis (N = 20) and extrahepatic portal hypertension (N = 20), and a control group (N = 20). A mild alteration of the recognition memory occurred in rats with cholestasis compared to control rats and portal hypertensive rats. The latter group showed the poorest performance on the basis of the behavioral indexes tested. In particular, only the control group spent significantly more time exploring novel objects compared to familiar ones (P < 0.001). In addition, the portal hypertension group spent the shortest time exploring both the novel and familiar objects (P < 0.001). These results suggest that the existence of portosystemic collateral circulation per se may be responsible for subclinical encephalopathy.

Animals↗

Portal hypertension: return to fetal life to re-attempt differentiation?

We speculate on the final meaning of the alterations that characterize portal hypertensive enteropathy. The similarity of these alterations with certain morphofunctional characteristics of prenatal splanchnic development makes it possible to hypothesize that the dedifferentiation with return to early stages of development could constitute a portal hypertension induced pathogenic mechanism.

Cell Differentiation↗

Posttraumatic inflammation is a complex response based on the pathological expression of the nervous, immune, and endocrine functional systems.

The successive phases that make up both the local and systemic posttraumatic acute inflammatory response could represent the expression of three concatenated pathological or "primitive" functional systems with trophic properties: the nervous, immune, and endocrine ones. The nervous functional system would play an important role in the phenomenon of ischemia-reperfusion, which would be represented by nutrition by diffusion that is either anaerobic (ischemia) or with defective use of oxygen (reperfusion) and, thus, with a limited energy requirement. The immune functional system would be represented by the infiltration of the tissues by inflammatory cells and bacteria, which would become mediators in providing nutrition to the injured tissues. Although the use of oxygen would still be defective, hypermetabolism and fever would occur. In these inflammatory response phases, the lymphatic is the most important circulation. The endocrine functional system would be the most specialized and would have high energy requirements because it would be represented by the blood capillary-mediated nutrition. Highly specialized epithelial cells would already possess a perfected oxidative metabolism. The successive expression of these three functional systems during embryonic development and also during the evolutionary development of our species could explain why the inflammatory response is a ubiquitous mechanism that is common to multiple diseases, because it is an integrator of the ontogeny and phylogeny.

Endocrine Glands↗

Budesonide ameliorates early portal hypertension in the rat: possible antiexudative splanchnic action.

Major portal pressure increase occurs on the second day post-stenosing-ligation of the portal vein in the rat and it is associated with pancreatic edema, intraperitoneal free exudate, hypoalbuminemia and hypoproteinemia. All this suggests the development of a regional exudative inflammatory response. In order to verify this hypothesis the steroid budesonide, whose antiinflammatory activity could prevent these alterations, was administered to rats with prehepatic portal hypertension. Wistar male rats were divided into the following groups: Control rats that were administered saline solution (CS; n = 10), Control rats that were administered budesonide (36 mg/kg per day; CB; n = 10), triple stenosing ligation of portal vein (TSLP) with saline solution (n = 10) and triple stenosing ligation of portal vein with budesonide (36 mg/kg per day; n = 10). In rats with prehepatic portal hypertension at 48 h of postoperative evolution, budesonide decreases the incidence of pancreatic edema, of peritoneal free exudate, of mesenteric adenopathies and prevents hypoproteinemia, hypoalbuminemia and hyper-beta-globulinemia. Some of the macroscopic intra-abdominal alterations and some of the changes in the electrophoretic pattern found in portal hypertensive rats could have an inflammatory etiopathogeny because budesonide shows an effective prophylaxis.

Journal Article↗

Altered proteinogram in short term portal vein stenosed rats.

The electrophoretic pattern of serum proteins has been studied in short-term prehepatic portal hypertensive rats since atrophy is produced in the liver, which is the main origin of most of these proteins, during this postoperative period. After 28 days of evolution, rats (n = 9) with triple stenosing ligated portal vein showed hypoalbuminemia, hypo-alpha-globulinemia, hyper-alpha2-globulinemia and hyper-gamma-globulinemia, the albumin/globulin ratio decreased with respect to the control animals (n = 8). These alterations are associated with hepatic atrophy, portosystemic and portohepatic (44.4%) collateral circulation. The proteinogram alterations found in rats with short-term prehepatic portal hypertension suggest that hepatic failure exists in spite of potential portohepatic revascularization which is frequently originated by the development of portohepatic collateral circulation.

Animals↗

Neuro-immune-endocrine functional system and vascular pathology.

A new interpretation of the response to injury by the nervous, immune and endocrine system is proposed, in order to integrate biochemical knowledge into the respective clinical areas. The discovery that the signaling molecules of the classical nervous, immune and endocrine systems, that is, the neurotransmitters, cytokines and hormones, respectively, are expressed and perceived by the three systems, has enabled us to establish a functional concept of these systems. The hypothetical integration of different pathological processes in a functional response made up by three phases, the immediate or nervous, intermediate or immune and late or endocrine ones, makes it possible to consider that all of them represent different forms of expression of a functional response whose meaning is always the same, that is, inflammation. If the functions that characterize each one of these three phases represent the activity of the nervous, immune and endocrine systems, the biochemical knowledge could be integrated into the functional meaning of each system.

Endocrine Glands↗

Increased duodenal mucosa infiltration by mast cells in rats with portal hypertension.

BACKGROUND: Enteropathy characterized by vascular and inflammatory alterations in the submucosa and mucosa has been described in patients with portal hypertension. AIMS: To verify the theory of inflammatory etiopathogenesis in experimental portal hypertensive duodenopathy, a prehepatic portal hypertension model based on the development of a single and triple partial ligation of the portal vein was used in the rat. METHODS: Five rats in each group (male Wistar, 230-255 g) were subjected to single (group II) or triple (group III) partial ligation of the portal vein and then compared to 5 control animals (group I, no operation). The animals were sacrificed 6 weeks later to analyze the histological parameters of the duodenal mucosa and submucosa, i.e., number, diameter and area of submucosal vessels, density of mast cells and mitotic cells. Body, liver and spleen weights and collateral circulation type were also assayed. RESULTS: As was demonstrated by the collateral circulation in all of the animals, the partial portal ligation was successful. Compared to the controls, the number of vessels per microscopic field (25 +/- 3.16 vs. 18.60 +/- 1.52), their diameter (20.09 +/- 2.90 vs. 12.61 +/- 3.97 microm, p < 0.05) and consequently their total area (12,749.30 +/- 2,298.26 vs. 3,455.82 +/- 1,702.33 microm2) were increased in the animals with a single partial ligation (group II) as well as in animals receiving triple partial ligation (group III) (33 +/- 12.88, p < 0.05; 22.92 +/- 6.72 microm, p < 0.05 and 51,376.95 +/- 43,732.24 miccrom2, p < 0.05, respectively). In addition, the density of mast cells increased from 3.26 +/- 1.18 in controls to 10.74 +/- 1.47, p < 0.01 and 22.50 +/- 6.42, p < 0.01 in single and triple partial portal ligated animals, respectively. Mitosis was significantly induced in crypts of the duodenal mucosa of the single portal ligated animals (25.20 +/- 1.78 vs. 17.40 +/- 1.14, p < 0.01) but was inhibited in triple partial ligated animals (12.40 +/- 5.12, p < 0.05). Compared to controls, both groups of rats developed liver atrophy with a greater decrease in the liver/body weight ratio in the single (2.71 +/- 0.50%, p < 0.01) compared to the triple partial ligated animals (3.33 +/- 0.09%, p < 0.01). CONCLUSIONS: The correlation of the degree of portal hypertension with the vascular changes and mast cell density suggests that both the hypertensive state and inflammation may play a role in the development of portal hypertensive intestinal vasculopathy. The inverse relation of portal hypertension with liver atrophy and mitosis rate in the crypts of the duodenal mucosa has not been clarified and should be investigated in future studies.

Analysis of Variance↗

Cytochrome oxidase activity in splanchnic organs of portal hypertensive rats.

OBJECTIVE: Portal hypertension is characterized by hyperdynamic splanchnic circulation associated with the development of portosystemic portal collateral circulation. Since blood flow regulation mechanisms in the splanchnic organs can be metabolic, its metabolic capacity has been studied using the mitochondrial enzyme cytochrome C oxidase as histochemical marker. METHOD: Cytochrome oxidase was quantified with a histochemical technique in the liver, pancreas and small bowel of Wistar rats in the control group (n = 8) and in rats with portal hypertension by triple stenosing ligation of the portal vein (n = 9) at 28 days of evolution. RESULTS: All rats with portal hypertension develop portosystemic collateral circulation. In these animals, cytochrome oxidase activity increases (p < 0.01) in the liver (left lateral lobe, periportal zone: 91.81 +/- 5.18 vs. 86.03 +/- 2.82) exocrine pancreas (125.6 +/- 7.25 vs 117.57 +/- 6.43; p < 0.05) as well as in the mucosa (crypts) and duodenum serosa, jejunum and ileum while it decreases in the pericentral zone of the hepatic acinus and intestinal villi. CONCLUSION: Cytochrome oxidase is considered an endogenous marker of local tissular metabolic capacity, so that its increased activity in the small bowel mucosa, crypts, exocrine pancreas and visceral peritoneum may be a metabolic factor that induces splanchnic hyperdynamic circulation in short-term portal hypertensive rats.

Animals↗

Increased plasma levels of corticosterone and prolactin and decreased T3 and T4 levels in short-term prehepatic portal hypertension in rats.

Corticosterone, T3, T4, and prolactin serum concentrations at 24 hr (N = 10), 15 days (N = 10), and 45 days (N = 10) of postoperative (postop) evolution were assayed to study the neuroendocrine response to portal hypertension. A triple stenosing ligature of the portal vein was used as the surgical technique of portal hypertension. This technique does not produce mortality and causes a decrease in the serum concentrations of T3 (0.043 +/- 0.009 vs 0.55 +/- 0.08 ng/ml) and T4 (3.93 +/- 0.55 vs 4.65 +/- 0.67 microg/ml) and an increase in those of prolactin (28.61 +/- 20.20 vs 12.84 +/- 3.96 ng/ml) and corticosterone (397.50 +/- 64.17 vs 311.53 +/- 57.41 ng/ml) at 45 days postop. The T3, T4, prolactin, and corticosterone alterations are associated with a persistent increase of TNF-alpha and NO, whose serum concentrations at 45 days postop are, respectively, 1838.33 +/- 247.07 vs 48.89 +/- 8.75 pg/ml and 0.43 +/- 0.13 vs 0.19 +/- 0.01 mmol/ml. TNF-alpha and NO could mediate these hormonal alterations in the evolution of short-term portal hypertension in the rat; thus they are involved in the systemic neuroendocrine response that is induced by this injury.

Animals↗

A new technique for tying the surgeon's knot.

A technique for tying the surgeon's knot is explained. This is based on considering that the active hand has two clasps, an inferior one formed by the thumb and the ring finger, which fixes the distal end of the ligature, and another superior clasp formed by the index and middle finger, whose rotating mobility makes it possible to wrap the proximal tips of the ligature around them one or more times and then to grasp the distal end and pull it through the proximal loops.

Humans↗

Hepatic cytochrome oxidase in rats with microsurgical cholestasis or portocaval shunt.

AIMS: portocaval shunt and extrahepatic cholestasis are experimental models of chronic hepatic insufficiency of different etiology and histological characteristics, and which probably also differ in the mechanism of impairment of oxidative metabolism. To test this hypothesis we measured hepatic cytochrome oxidase. METHODS: cytochrome oxidase was assayed with a histochemical technique in three groups of Wistar rats: A (n = 8) control; B (n = 8) microsurgical extrahepatic cholestasis; and C (n = 8) end-to-side portocaval shunt. RESULTS: cytochrome oxidase activity was lowest in group B, both in the left middle (p = 0.00019) and in the inferior caudate (p = 0.00014) hepatic lobes, and was highest in group C in both hepatic lobes, especially in the left middle lobe (p = 0.0029). CONCLUSION: the decrease in cytochrome oxidase activity in the liver of rats with extrahepatic cholestasis and the increase in animals subjected to portal flow deprivation demonstrate the different nature of the impairment in hepatic oxidative metabolism in these two pathological conditions.

Animals↗