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Biomedical subjects

A Ayala

Publications and source records attributed to A Ayala.

At least 109 records · Page 6Linked to original sources
PubMed1997

Mechanism of intestinal mucosal immune dysfunction following trauma-hemorrhage: increased apoptosis associated with elevated Fas expression in Peyer's patches.

Although intestinal mucosal immune dysfunction occurs after trauma and hemorrhage and appears to contribute to infectious complications, the mechanism is not known. In this regard, the inappropriate induction of immune cell apoptosis may contribute to the immune dysfunction following trauma and hemorrhage. To study this, we examined Peyer's patch cells for evidence of apoptosis and changes in Fas protein expression, as well as alterations in the relative lymphocyte subpopulations after trauma and hemorrhagic shock. Male C3H/HeN mice underwent sham operation, trauma (i.e., laparotomy), hemorrhagic shock (mean arterial blood pressure of 35 +/- 5 mmHg for 90 min, followed by adequate crystalloid resuscitation), or trauma plus hemorrhage. Peyer's patch cells were isolated at 24 and 72 hr after the procedure. The percentage of apoptotic cells, Fas protein expression, and cell percentage of phenotype were determined by flow cytometry. The results indicate that trauma alone induced no significant change in the measured parameters. However, (i) there were a significant decrease in total viable cell yield and an increased apoptosis in Peyer's patch cells at 24 and 72 hr following hemorrhage or trauma plus hemorrhage; (ii) the increased apoptosis in Peyer's patch was predominantly in cells of the B-cell lineage; (iii) the increased apoptosis was associated with an elevated Fas expression. In conclusion, hemorrhage alone or trauma plus hemorrhage can induce increased apoptosis in Peyer's patch cells, which is associated with the increased Fas expression. Thus, apoptotic involution may play an important role in the depression of intestinal mucosal immune function after trauma and hemorrhagic shock.

Animals↗
PubMed1997

The role of neutrophils in producing hepatocellular dysfunction during the hyperdynamic stage of sepsis in rats.

Although studies have shown that hepatocellular function is depressed during the early, hyperdynamic stage of sepsis, the mechanism responsible for this remains unknown. To determine whether neutrophils play any role in producing this depression, hepatocellular function was measured in neutrophil-competent and neutropenic animals subjected to sepsis. Neutropenia was induced by tail vein injection of an immunoglobulin directly against rat neutrophils (anti-neutrophil Ig) at 16 and 2 h prior to the initiation of cecal ligation and puncture (CLP, i.e., a model of polymicrobial sepsis). Neutropenia was confirmed by peripheral blood smears. Neutrophil-competent controls were given nonimmunized Ig before the onset of sepsis. Sham-operated animals received anti-neutrophil Ig or control Ig. Hepatocellular function [i.e., the maximal velocity of indocyanine green clearance (Vmax) and efficiency of the clearance (Km)] was determined by a fiber-optic catheter and in vivo hemoreflectometer at 5 h after CLP (i.e., early, hyperdynamic sepsis) or sham operation. Serum alanine aminotransferase (ALT) levels were also determined. The results indicate that although circulating levels of ALT were not elevated, hepatocellular function was significantly depressed during early sepsis. The depression in Vmax and Km was, however, prevented by neutrophil depletion, suggesting an integral role of the neutrophils in depressing hepatocellular function under such conditions. The results suggest that the prudent modulation of neutrophil function during the early stage of polymicrobial sepsis may be beneficial for preventing or delaying the occurrence of hepatocellular dysfunction.

Alanine Transaminase↗
PubMed1997

Acute abdomen in systemic lupus erythematosus: the importance of early laparotomy.

BACKGROUND: Acute abdomen (AA) in systemic lupus erythematosus (SLE) is a challenging diagnostic and therapeutic problem. Most patients are on steroid and/or immunosuppressive treatment and mortality is high. METHODS: We assessed the relationship between the causes of AA in SLE and the SLE disease activity index (SLEDAI). RESULTS: Of 51 patients with SLE and AA, 36 had active disease (Group 1) and 15 inactive disease (Group 2). Group 1 included 19 patients with vasculitis (mean SLEDAI 15.4, range 13 to 24). Three patients with intraabdominal thrombosis and high titers of anticardiolipin antibodies (mean SLEDAI 18.3) and 14 patients with non-SLE-related AA (SLEDAI 8.2, range 5 to 11). Group 2 consisted of 15 inactive SLE patients (mean SLEDAI 1.7, range 0 to 4). Mortality was high in the active group (14 patients) compared with inactive SLE (2 cases). A delay in surgical exploration (39.3 vs 178.6 hours) had a negative influence on the prognosis. CONCLUSIONS: In SLE patients with AA, a SLEDAI score below 5 is indicative of non-SLE-related AA. Elevated aCL were found in patients with intraabdominal thrombosis. AA in inactive SLE is non-SLE-related and has low mortality, provided an appropriate surgical treatment is given. Early laparotomy influences positively the prognosis of SLE patients with AA.

Abdomen, Acute↗
PubMed1997

Low selenium diet increases the dopamine turnover in prefrontal cortex of the rat.

It has been proposed that interaction of catecholamines and indoleamines with free radicals may result in the formation of endogenous neurotoxins. In order to better understand the mechanisms involved in neurodegenerative disorders showing evidence of oxidative stress, we have studied the basal concentrations and the turnover rates of dopamine, noradrenaline, serotonin and their metabolites in the prefrontal cortex of rats that were fed on control or low selenium diets. Nutritional deficit of selenium decreases the brain antioxidant protection in experimental conditions by the decrease in glutathione peroxidase activity. The dopamine and serotonin turnover increased and noradrenaline and 5-hydroxy-3-indoleacetic acid turnover decreased compared to experimental control animals. The increase of dopamine turnover in experimental rats was accompanied by an increase in tyrosine hydroxylase activity. These results suggest that the decrease of brain protection against oxidative damage could induce brain damage by disturbing the turnover rate of some monoamines.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Neutral and acid mucins and eosinophil and argyrophil crystalloids in carcinoma and atypical adenomatous hyperplasia of the prostate.

Neutral and acid mucins and eosinophil and argyrophil crystalloids were studied in the glandular intraluminal contents of 130 prostatic carcinomas (PCa) and 22 atypical adenomatous hyperplasias (AAH). Specimens were studied in the usual extension for diagnostic purposes and considered positive when minimal amounts of mucin or any crystalloid were present. Some amount of altered secretion was seen in 110 PCa (84.6%) and in 17 AAH (77.3%); the similarity of the figures speaks for the close relationship of these lesions. The relative incidences in PCa/AAH were 61.5%/77.3% for neutral mucin, 80%/54.5% for acid mucin (p < 0.01), 25.4%/50% for eosinophil crystalloids (p < 0.02), 44.6%/9.1% for argyrophil crystalloids (p < 0.01) and 57%/36% for a compound secretion. The incidence of eosinophil crystalloids was greater in AAH and inversely proportional to the Gleason grade in PCa. The incidence of acid mucins and argyrophil crystalloids was higher in PCa and directly proportional to the tumour grade in all but the poorly differentiated ones. It is therefore suggested that AAH positive for acid mucins or argyrophil crystalloids be classified in the high grade AAH group.

Aged↗
PubMed1997

Meningeal melanocytoma: case report and review of the literature.

We report a case of meningeal melanocytoma in the thoracic spinal cord of a 44-year-old woman and review previously documented cases. Our patient experienced numbness and tingling in her left leg for 8 years, and low back pains with intermittent claudication for the previous 2 months. A histologically benign 20-mm tumour was totally resected. Radiation therapy was not given. The tumour showed the histological, immunohistochemical and ultrastructural features of a meningeal melanocytoma. The patient is alive without recurrence 4.5 years after surgery.

Adult↗
PubMed1997

Adenosine decreases post-ischaemic cardiac TNF-alpha production: anti-inflammatory implications for preconditioning and transplantation.

Tumour necrosis factor-alpha (TNF-alpha) is an autocrine contributor to myocardial dysfunction and cardiomyocyte death in ischaemia-reperfusion injury (I/R), sepsis, chronic heart failure and cardiac allograft rejection. Cardiac resident macrophages, infiltrating leucocytes, and cardiomyocytes themselves produce TNF-alpha. Although adenosine reduces macrophage TNF-alpha production and protects myocardium against I/R, it remains unknown whether I/R induces an increase in cardiac TNF-alpha in a crystalloid-perfused model (in the absence of blood), and, whether adenosine decreases cardiac TNF-alpha and protects function after I/R. To study this, isolated rat hearts were crystalloid-perfused using the Langendorff method and subjected to I/R, with or without adenosine pretreatment. Post-ischaemic cardiac TNF-alpha (enzyme-linked immunosorbent assay and bioassay) and function were determined (Langendorff). I/R increased cardiac TNF-alpha and impaired myocardial function. Adenosine decreased cardiac TNF-alpha and improved post-ischaemic functional recovery. This study demonstrates that: first, I/R induces an increase in cardiac tissue TNF-alpha in a crystalloid-perfused model: second, adenosine decreases cardiac TNF-alpha and improves post-ischaemic myocardial function; third, decreased cardiac TNF-alpha may represent a mechanism by which adenosine protects myocardium; and fourth, adenosine-induced suppression of cardiac TNF-alpha may provide an anti-inflammatory link to preconditioning and have implications for cardiac allograft preservation.

Adenosine↗
PubMed1997

Females in proestrus state maintain splenic immune functions and tolerate sepsis better than males.

OBJECTIVES: To determine: a) whether the cell-mediated immune response during sepsis differs in females vs. males; and b) whether the survival rate in females is different than in males after a septic insult. DESIGN: A prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: Male and female proestrus C3H/HeN mice. INTERVENTIONS: After anesthesia, male and proestrus female mice underwent cecal ligation puncture to induce sepsis. The mice were killed at 24 hrs after the onset of sepsis. MEASUREMENTS AND MAIN RESULTS: Splenocyte proliferation, as well as splenocyte interleukin (IL)-2 and IL-3 release, was determined by bioassay. In additional studies, survival rate after septic challenge was measured over 10 days. Splenocyte proliferative capacity and splenocyte IL-2 and IL-3 release were markedly decreased in male, but not in female, septic mice. Furthermore, the survival rate of septic female proestrus mice was significantly higher than in comparable male mice. CONCLUSIONS: These results support the concept that the immune response of females differs from males, and that females are immunologically better positioned to meet the challenge of sepsis.

Adolescent↗
PubMed1997

Mechanism of splenic immunosuppression during sepsis: key role of Kupffer cell mediators.

Studies indicate that the liver, in particular the Kupffer cells, appear to be key contributors in the systemic inflammatory mediator response associated with shock and sepsis. Although several of these agents have been implicated as mediators of depressed immunoresponsiveness observed during sepsis, it remains unknown whether or not mediators released specifically by Kupffer cells play any significant role in producing the cellular dysfunction in distant organs. The aim of this study, therefore, was to determine whether or not acute Kupffer cell reduction before the onset of sepsis would protect splenic lymphocyte function. Kupffer cell number was reduced by prior (48 hours) treatment of mice with gadolinium chloride (GdCl2, 10 mg/kg of body weight, intravenously) or saline vehicle. Animals were then subjected to either sham-CLP (sham) or polymicrobial sepsis in the form of cecal ligation and puncture (CLP). Plasma and splenocytes were harvested at 2 or 24 hours after CLP. Splenocyte cultures were exposed to 2.5 micrograms concanavalin A/mL to assess their ability to release lymphokines. Cytokine (interleukin (IL)-2, IL-6, interferon-gamma, tumor necrosis factor-alpha) concentration in plasma or cell supernatants was assessed by bioassay. The results indicated that GdCl2 treated mice exhibited a marked reduction in circulating IL-6 levels at both 2 and 24 hours after CLP. Furthermore, the reduction of Kupffer cell number before the onset of sepsis completely prevented the depression of splenocyte IL-2 and interferon-gamma release, capacity. Thus mediators released by Kupffer cells during the systemic inflammatory response to polymicrobial sepsis play a significant role in producing immune dysfunction in resident splenic lymphocytes. In view of this, it appears that modulation of Kupffer cell hyperactivity during sepsis may be a novel approach for maintaining distant organ host defense mechanisms.

Animals↗
PubMed1997

Male sex steroids are responsible for depressing macrophage immune function after trauma-hemorrhage.

Recent studies suggest beneficial effects of castration before soft tissue trauma and hemorrhagic shock on splenocyte immune functions. Nonetheless, it remains unknown whether this effect of testosterone depletion is limited to splenocytes or is a generalized effect on immune function. The present study was therefore carried out to determine whether androgen depletion before trauma-hemorrhage also has salutary effects on splenic and peritoneal macrophage as well as on Kupffer cell function, as indicated by interleukin (IL)-1 and IL-6 release. Male C3H/HeN mice were castrated or sham-castrated 2 wk before the experiment and were killed at 24 h after trauma-hemorrhage and resuscitation. Significant depression of macrophage IL-1 and IL-6 release was only observed in sham-castrated mice, as opposed to normal levels of cytokine release from castrated animals after trauma-hemorrhage. In addition, only sham-castrated animals showed significantly increased levels of IL-6 release from Kupffer cells, which is believed to contribute to the systemic inflammatory response to trauma-hemorrhage. These observations suggest that the beneficial effects of androgen depletion before trauma-hemorrhage are not limited to splenocyte immune functions but are more global in nature. These results in surgically castrated animals suggest that androgen-blocking agents should be studied for their potential to reverse the immunodepression associated with trauma-hemorrhage.

Androgens↗
PubMed1997

Flutamide: a novel agent for restoring the depressed cell-mediated immunity following soft-tissue trauma and hemorrhagic shock.

Recent studies indicate beneficial effects of androgen depletion in male mice, before trauma-hemorrhage on cell-mediated immunity following soft-tissue trauma and hemorrhagic shock. Nonetheless, it remains unknown whether androgen receptor blockade following the insult has any salutary effects. To study this, male C3H/HeN mice were either sham-operated or subjected to soft-tissue trauma (i.e., 2.5 cm midline laparotomy) followed by hemorrhagic shock (blood pressure 35 +/- 5 mmHg for 90 min) and then adequately resuscitated (shed blood and lactated Ringer's). Immediately after the completion of resuscitation, as well as 24 and 48 h thereafter, the animals received either vehicle, 10 mg/kg body weight (BW) flutamide or 25 mg/kg BW flutamide subcutaneously. At 72 h after resuscitation, all animals were killed. The spleens and peritoneal macrophages (M phi) were then harvested and cultures established to determine IL-2 and IL-3 release, splenocyte proliferative capacity, as well as splenic and peritoneal M phi IL-1 release. Moreover, plasma testosterone and corticosterone levels were measured. Our results indicate that trauma-hemorrhage resulted in significant depression of splenocyte and M phi functions in vehicle-treated and animals receiving 10 mg/kg BW flutamide. Treatment with 25 mg/kg BW flutamide following trauma-hemorrhage, however, resulted in levels of cytokine release which were comparable with those found in sham-operated animals. No significant alterations in plasma corticosterone and testosterone levels were observed in any of the experimental groups. These findings indicate that short-term therapy of males with the androgen receptor blocker, flutamide at 25 mg/kg BW, following trauma-hemorrhage has protective effects on immune functions. This protective effect is dose dependent, since 10 mg/kg BW flutamide did not produce significant salutary effects. Thus, flutamide represents a novel and safe agent for improving the depressed functions in male trauma patients suffering severe blood loss.

Animals↗
PubMed1996

Prolactin administration following hemorrhagic shock improves macrophage cytokine release capacity and decreases mortality from subsequent sepsis.

Although prolactin is reported to counteract the immunosuppressive effects of glucocorticoids, cyclosporine, and morphine, it remains unknown whether prolactin has any salutary effects on the depressed immune responses following severe hemorrhage. To study this, mice were bled to and maintained at a mean arterial pressure of 35 mm Hg for 60 min, then adequately resuscitated and divided into two groups. One group received saline vehicle, while the other group received prolactin (100 micro g/25 g body weight, s.c.) immediately before resuscitation. Two hours thereafter, peritoneal (pMphi) and splenic macrophages (sMphi) were harvested and assessed not only for their ability to release IL-1 and IL-6, but also for cytokine gene expression using semiquantitative reverse transcription and PCR. In an additional group, mice were subjected to sepsis by cecal ligation and puncture 3 days after hemorrhage. Hemorrhage markedly decreased the ability of pMphi and sMphi to release IL-1 and IL-6. This was, however, associated with increased mRNA expression for IL-1beta and IL-6 and increased serum corticosterone levels. Following prolactin treatment of hemorrhaged mice, IL-1beta and IL-6 mRNA levels as well as cytokine release capacity and blood corticosterone levels were comparable to the values in sham animals. Prolactin also improved the survival of animals subjected to sepsis after hemorrhage. Thus, the immunosuppression following hemorrhage appears to be mediated and modulated by hormones from the hypothalamic-pituitary-adrenal axis. Furthermore, prolactin represents a novel immunomodulating hormone for the treatment of immunodepression encountered after hemorrhagic shock and for decreasing the mortality from subsequent sepsis under those conditions.

Animals↗
PubMed1996

Effect of oxidative stress, produced by cumene hydroperoxide, on the various steps of protein synthesis. Modifications of elongation factor-2.

We have studied the effect of oxidative stress on protein synthesis in rat liver. Cumene hydroperoxide (CH) was used as an oxidant agent. The approach used was to determine the ribosomal state of aggregation and the time for assembly and release of polypeptide chains in the process of protein synthesis in rat liver in vivo. The results suggest that the elongation step is the most sensitive to CH treatment. The measurement of both carbonyl groups content and ADP-ribosylatable elongation factor 2 (EF-2), the main protein involved in the elongation step, indicates that under CH treatment EF-2 is oxidatively modified and a lower amount of active EF-2 is present. These results are corroborated by in vitro oxidation of EF-2 and could explain for the decline in the elongation step.

Adenosine Diphosphate Ribose↗
PubMed1996

Increased melatonin levels after hemorrhagic shock in male and female C3H/HeN mice.

Although hemorrhagic shock leads to significant alterations of several hormones, e.g. ACTH, corticosterone and beta-endorphin, it is not known whether plasma melatonin levels are affected under this condition and if so, whether the effects are comparable in males and females. Using a radioimmunoassay, it was found that plasma melatonin levels were significantly increased in male and proestrus female C3H/HeN mice immediately after hemorrhagic shock. However, in male mice, by two hours after hemorrhage and resuscitation, plasma melatonin returned to levels comparable to those seen in control and sham-operated animals. Proestrus female mice, on the other hand, showed significantly increased plasma melatonin levels at two hours after surgery when compared to unoperated control animals. Although the significance and biological role of the transient increased plasma melatonin levels after hemorrhagic shock remain to be determined, it appears that the pineal gland and/or an extrapineal source of melatonin, of both male and proestrus female mice responds to severe hypotension by increased release of melatonin.

Animals↗
PubMed1996

Differential induction of apoptosis in lymphoid tissues during sepsis: variation in onset, frequency, and the nature of the mediators.

Apoptosis (Ao), is a process by which cells undergo a form of nonnecrotic cellular suicide. Although for most cells this is a constitutive process, it can be induced in immature and differentiating immune cell populations by stress mediators associated with inflammation. This inducible form of A(o) is referred to as programmed cell death. However, it is not clear whether hematopoietic cell populations such as the thymus and bone marrow are induced to undergo A(o) during polymicrobial sepsis. To assess this, thymocytes, bone marrow cells, or splenocytes (as a source of comparative nonhematopoietic cells) were harvested from C3H/HeN mice at 1, 4, or 24 hours after cecal ligation and puncture (CLP; to induce polymicrobial sepsis) or sham-CLP (Sham). The results showed that mixed bone marrow cells ex vivo, although not to the same extent as thymus, showed a marked increase in the percentage of cells in A(o), increased endonuclease activity, and a significant decrease in cell yield at 24 hours but not at 4 hours after CLP. Similar changes were not evident in splenocytes. Phenotypic, as well as morphologic assessment, indicated that most of the increase in apoptotic cells in the thymus was associated with the immature T cells (CD4+CD8+) and CD8-CD4- cells. In contrast, the increase in bone marrow cell A(o) was associated with only the B220+ cells, with no significant contribution from myeloid cells. Treatment of CLP mice in vivo with either RU-38486 or PEG-(rsTNF-R1)2 was unable to reverse the increased A(o) in the bone marrow of these animals. Taken together, these findings indicate that A(o) as a process induced by polymicrobial sepsis is not limited to the thymus, but can also be detected in the bone marrow. However, unlike thymic A(o), bone marrow is not affected directly/indirectly by glucocorticoids or tumor necrosis factor released during sepsis.

Animals↗
PubMed1996

Immune function is more compromised after closed bone fracture and hemorrhagic shock than hemorrhage alone.

OBJECTIVE: To determine whether closed bone fracture in conjunction with hemorrhagic shock compromises immune functions more severely than hemorrhagic shock alone. DESIGN: In a randomized, controlled trial, closed bone fracture of the right lower leg and/or hemorrhagic shock (mean +/- SEM arterial blood pressure, 35 +/- 5 mm Hg for 90 minutes) were induced in male C3H/HeN mice (weight, 25 g). Animals subjected to hemorrhage were resuscitated with the shed blood and lactated Ringer solution. At 72 hours after the experiment, all animals were killed to obtain whole blood, splenocytes, and splenic and peritoneal macrophages. Macrophage interleukin-1 and splenocyte interleukin-2 and interleukin-3 release were determined by bioassay, and splenocyte proliferation was measured by tritiated thymidine incorporation. RESULTS: Closed bone fracture alone did not affect immune functions 72 hours after the trauma. Hemorrhagic shock, however, induced a significant depression of splenocyte and macrophage functions. Bone fracture followed by hemorrhagic shock further depressed splenocyte proliferation and splenocyte interleukin-2 and interleukin-3 release as well as interleukin-1 release. CONCLUSION: Since bone injury coupled with hemorrhagic shock produces more severe depression of immune functions than hemorrhage alone, bone injury appears to play a contributory role in further depressing immune functions in trauma patients who experience major blood loss.

Animals↗