Search PubMed⌕ Search

Biomedical subjects

A Ayala

Publications and source records attributed to A Ayala.

At least 163 records · Page 9Linked to original sources
PubMed1994

Reduction of 1-methyl 1,2,3,4-tetrahydroisoquinoline level in substantia nigra of the aged rat.

The compounds 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTIQ) are endogenous in humans and rats. Whereas TIQ seems to have neurotoxicity, 1-MeTIQ has been described as having a protective effect. In this paper, we report the concentration of TIQ and 1-MeTIQ in two areas especially influenced by aging and Parkinson's disease, the substantia nigra (SN) and striatum (ST), of the rat at different ages. 1-MeTIQ and TIQ were detected in both structures using gas chromatography-mass spectrometry with the higher content of both being in the SN. During the aging process there is a significant decrease (50%) in 1-MeTIQ levels in the SN, but TIQ levels did not change significantly in either of the studied regions.

Aging↗
PubMed1994

Mechanism of enhanced susceptibility to sepsis following hemorrhage. Interleukin-10 suppression of T-cell response is mediated by eicosanoid-induced interleukin-4 release.

OBJECTIVES: To determine (1) whether interleukin-10 (IL-10) contributes to depressed T-cell responses observed following hemorrhage and (2) what effect other immunosuppressive agents known to play a role in hemorrhage have on IL-10 release. DESIGN: Hemorrhage was induced in C3H/HeN mice. The mice were resuscitated and then killed 2 hours after hemorrhage to obtain plasma, splenocytes, splenic macrophages, and splenic T cells. RESULTS AND CONCLUSIONS: Decreased splenocyte/T-cell proliferation was associated with enhanced release of IL-10 by cells from hemorrhaged mice. However, unlike T cells, IL-10 release by macrophages was not comparatively elevated. While no changes were seen in systemic plasma levels of IL-10, the role of IL-10 as a localized immunosuppressant was demonstrated by the ability of IL-10 monoclonal antibody to restore T-cell proliferation following hemorrhage. Furthermore, elevated IL-10 release was prevented by the addition of ibuprofen or monoclonal antibody against transforming growth factor beta or IL-6. Since these agents have direct or indirect influences on prostanoid synthesis, studies were carried out examining the capacity of varying concentrations of prostaglandin E2 (PGE2) to augment IL-10 release by murine cloned Th2 cells (D10.G4.1) and by T cells from sham-operated or hemorrhaged mice. While the addition of PGE2, 10(-9) mol/L, potentiated the release of IL-10, this effect appears to be indirect, since the incorporation of monoclonal antibody to IL-4 prevented the release of IL-10 by PGE2-treated cells from sham-operated or hemorrhaged mice. Such a mechanism of eicosanoid-induced IL-4/IL-10 cell-mediated immunosuppression may directly contribute to the decreased capacity to ward off infectious challenge seen following hemorrhage.

Animals↗
PubMed1994

Energetics of lymphocyte "burnout" in late sepsis: adjuvant treatment with ATP-MgCl2 improves energetics and decreases lethality.

Although it is known that decreased high-energy phosphates contribute to organ dysfunction following shock, it remains unknown whether changes in lymphocyte energetics contribute to the profound immune dysfunction that occurs in late septic shock. Moreover, while studies have shown that ATP-MgCl2 treatment after hemorrhagic shock improves tissue ATP levels and organ function, it remains unknown whether lymphocyte high-energy phosphates and immune functions are similarly affected by this agent after sepsis. To study this, sepsis was induced in C3H/HeN (endotoxin sensitive) mice by cecal ligation and puncture (CLP) and they were then treated intraperitoneally with ATP-MgCl2 or saline vehicle. Sham animals received laparotomy, but not CLP. Splenic lymphocytes were harvested 24 hr after treatment and ATP levels were determined by ultraresolution 31P NMR. Lymphocyte proliferative capacity was determined by [3H]-thymidine incorporation following mitogenic stimulation. Host survival was assessed following CLP with and without ATP-MgCl2 treatment. Prolonged sepsis caused a significant decrease (decreases 67 +/- 12% vs Sham) in lymphocyte ATP levels which were correlated with decreased lymphocyte proliferative capacity in response to mitogenic stimulation (64 +/- 17 x 10(3) vs. 232 +/- 43 x 10(3) counts per minute (cpm) in Sham; P < 0.05). Treatment with ATP-MgCl2 at the onset of sepsis significantly increased lymphocyte ATP levels (increases 32 +/- 15% vs CLP) and proliferative response to mitogenic stimuli (218 +/- 37 x 10(3) cpm, CLP/ATP-MgCl2; P < 0.05). Improved lymphocyte function in this group correlated with a significant increase in overall survival (20% CLP vs 70% CLP/ATP-MgCl2; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1994

Pentoxifylline attenuates oxygen-induced lung injury.

Patients requiring mechanical ventilation can develop severe pulmonary injury. Although pentoxifylline (PTX) is known to attenuate endotoxin and tumor necrosis factor (TNF)-induced lung injury, as well as decrease interleukin-6 (IL-6) levels following hemorrhage and resuscitation, it remains unknown if this agent has any beneficial effects against O2-induced lung injury. The aim of this study, therefore, was to determine if PTX attenuates pulmonary oxygen toxicity. To investigate this, male Sprague-Dawley rats were injected subcutaneously with 1 ml saline or 1 ml PTX (50 mg/kg) and immediately exposed to either 21% O2 or > or = 95% O2 for 52 hr. The animals were then reweighed and euthanized. Pleural fluid was collected, blood samples were obtained, and lung lavage was performed. Lactate dehydrogenase (LDH) activity, protein content, and IL-6 concentrations were determined in the lavage fluid and serum. The supernatant LDH activity, protein content, pleural fluid accumulation, and IL-6 concentration were significantly decreased (P < 0.05) in those animals pretreated with PTX prior to exposure to hyperoxia compared to those animals exposed to hyperoxia and not treated. Furthermore, the hematocrit and serum IL-6 concentration were also decreased in the treated group and not significantly different from the controls. Thus, PTX appears to attenuate O2-induced lung injury and may play a role in protecting those patients at risk for developing pulmonary oxygen toxicity.

Animals↗
PubMed1994

Polymicrobial sepsis but not low-dose endotoxin infusion causes decreased splenocyte IL-2/IFN-gamma release while increasing IL-4/IL-10 production.

Although studies indicate that polymicrobial sepsis produces marked depression in lymphocyte functions, it remains unclear whether this dysfunction is due to the chronic exposure of immune cells to endotoxin (ETX; a product of the gram-negative bacterial cell wall) at levels typically encountered in the septic state. The aim of this study, therefore, was to determine whether the changes in lymphokine release seen during polymicrobial sepsis are comparable to those observed with chronic ETX infusion. To assess this, splenocytes were harvested from C3H/HeN mice (ETX-sensitive) at 1 or 24 hr following cecal ligation and puncture (CLP; to induce polymicrobial sepsis), Sham CLP (Sham), or laparotomy followed by peritoneal implantation of a mini-osmotic pump which delivered either saline vehicle (Sal-pump) or ETX (ETX-pump; 0.025 micrograms lipopolysaccharide/25 g body wt/24 hr). Splenocytes were then stimulated with concanavalin A (2.5 micrograms/ml/48 hr) and their capacity to release interleukin (IL)-2, interferon (IFN)-gamma, IL-4, and IL-10 was determined by bioassay or ELISA. The results indicated that there were no changes in lymphokine release capacity at 1 hr after CLP or ETX-pump implantation. However, prolonged sepsis (i.e., at 24 hr) caused a marked suppression of IL-2 and IFN-gamma release (immune-enhancing lymphokines characteristic of Th1-cells), while enhancing the release of immunosuppressive Th2-cell products IL-4 and IL-10. Chronic exposure to ETX at a level comparable to that seen in CLP caused no depression in lymphokine (IL-2/IFN-gamma) release. This implies that a bacterial component other than ETX mediates the differential alterations observed in lymphokine release during prolonged polymicrobial sepsis.

Animals↗
PubMed1994

Dextran 70 administration after trauma-hemorrhagic shock does not impair cellular immune functions.

PURPOSE: Although the effects of the colloid dextran 70 on induction of anaphylactoid reactions or reticuloendothelial phagocytosis have been examined previously, its effects on specific cell-mediated immunity after trauma-hemorrhage shock remain unknown. METHODS: Nonheparinized C3H/HeN mice underwent a laparotomy, were bled, and then maintained at a blood pressure of 35 mm Hg for 60 minutes. Then they were resuscitated with either 4 x the shed blood volume as lactated Ringer's solution (LRS) or 2 x LRS + 1 x dextran 70. Control mice underwent all operative protocols but were neither hemorrhaged, nor resuscitated. At 2 or 24 hours posthemorrhage, serum, splenocytes (SPL), and peritoneal macrophages (pM phi, splenic Mo (sM phi) were obtained. Bioassays were used to determine interleukin-2 (IL-2), IL-3, IL-6, and SPL proliferation. RESULTS: Trauma-hemorrhage markedly depressed lymphokine release, splenocyte proliferation, and IL-6 release at 2 hours after the insult. The combination of LRS + dextran did not restore lymphocyte functions, but also did not further suppress them. The release of IL-6 by pM phi and sM phi at 2 and 24 hours after dextran infusion and serum IL-6 remained at the same level as in LRS-treated animals. CONCLUSIONS: The combination of LRS and colloid dextran 70 does not adversely affect ex vivo cell-mediated immune functions during the first 24 hours after its administration after trauma-hemorrhage. Thus, from the immunological standpoint, dextran is a safe resuscitation adjunct.

Analysis of Variance↗
PubMed1994

Biological significance of elevated TNF levels: in vivo administration of monoclonal antibody against tnf following haemorrhage shock increases the capacity of macrophages to release TNF while restoring immunoresponsiveness.

Haemorrhagic shock results in a severe depression of the cellular and humoral immunity, thus rendering the host increasingly susceptible to sepsis. To study the effect of elevated TNF release following haemorrhagic shock on depressed macrophage and splenocyte functions, C3H/HeN mice were pretreated intraperitoneally with either anti-murine TNF-Ab or saline. Twenty hrs later, mice were bled to and maintained at a mean BP of 35 mmHg for 60 min followed by adequate fluid resuscitation. Pretreatment with anti-TNF-Ab completely neutralized elevated TNF plasma levels following haemorrhage. This was associated with an increased (P < 0.05) capacity of pMø isolated 24 h after haemorrhagic shock to release TNF, while the ability to secrete IL-6 and PGE2 was reduced. Haemorrhagic shock-induced suppression of pMø antigen presentation capacity and MHC class II antigen expression, as well as depression of splenocyte proliferation and lymphokine production was also attenuated (P < 0.05) by anti-TNF-Ab pretreatment. These data indicate that elevated circulating TNF levels play a pivotal role in the depression of essential macrophage and splenocyte functions following haemorrhagic shock.

Animals↗
PubMed1994

Effects of trauma, duration of hypotension, and resuscitation regimen on cellular immunity after hemorrhagic shock.

OBJECTIVE: To determine the effects of: a) surgical trauma, b) crystalloid resuscitation, and c) different durations of hypotension on cellular immunity after hemorrhagic shock. DESIGN: Prospective, multiexperimental, randomized, controlled studies. SETTING: University research laboratory. SUBJECTS: Inbred C3H/HeN (endotoxin-sensitive) mice, aged 6 to 7 wks, weighing 18 to 23 g. INTERVENTIONS: Crystalloid resuscitation, with and without blood, after hemorrhage. MEASUREMENTS AND MAIN RESULTS: Mice which did or did not undergo laparotomy were subjected to hypotension of 35 mm Hg for 60 or 90 mins. Crystalloid resuscitation with and without blood was then provided. Animals were killed at 2 hrs after hemorrhage and cytokine concentrations in supernatants of splenocytes, splenic macrophages, and serum were assessed by bioassays. The cellular release of interleukin (IL)-2, IL-3, IL-6, tumor necrosis factor, and the splenocyte proliferative capacity were significantly and similarly depressed in all groups. Conversely, circulating IL-6 concentrations were significantly increased in all groups. CONCLUSIONS: Cellular immunity was depressed at 2 hrs after simple hemorrhage and no further depression occurred if hemorrhage was coupled with trauma, pure crystalloid resuscitation was provided, or the shock period was prolonged. Thus, the early immunodepression after hemorrhage was mainly dependent on the severity rather than the duration of shock, resuscitation regimen, or tissue trauma.

Animals↗
PubMed1994

Role of Kupffer cells in interleukin-6 release following trauma-hemorrhage and resuscitation.

Although interleukin-6 (IL-6) plays an important role in the pathophysiology of trauma-hemorrhage and resuscitation, the cellular origin of this inflammatory cytokine remains unknown. This study was undertaken to determine whether Kupffer cells (KC) are a major source of IL-6 release following trauma-hemorrhage and resuscitation. KC numbers were significantly (p < .05) reduced in vivo with gadolinium chloride (GdCl3; 10 mg/kg IV). KC-reduced (KC(-)) and KC-normal (saline-treated; KC(+)) rats underwent laparotomy (i.e., trauma-induced), followed by either sham operation or hemorrhage. Hemorrhaged rats were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of the shed blood volume was returned as Ringer's lactate, and then resuscitated with Ringer's lactate (four times shed blood volume over 1 h). Results indicate that KC reduction per se had no effect on any measured parameter at any time. At 0.5 and 2.0 h postresuscitation, mean arterial pressure, heart rate, cardiac output, stroke volume, and hematocrit were reduced to a similar extent in both the KC(+) and KC(-) hemorrhage groups. KC reduction did, however, significantly reduce plasma IL-6 concentration (means +/- S.E.; U/ml) at both 0.5 h (KC(+) = 709 +/- 391 vs. KC(-) = 159 +/- 5) and at 2.0 h (KC(+) = 527 +/- 394 vs. KC(-) = 83 +/- 20) postresuscitation. In conclusion, this study demonstrates that KC are a major source of in vivo IL-6 release following trauma-hemorrhage and resuscitation.

Animals↗
PubMed1994

Evidence favoring the role of the gut as a cytokine-generating organ in rats subjected to hemorrhagic shock.

There is increasing evidence of an association between intestinal injury and the development of a septic state and distant organ failure. Since this phenomenon can occur in the absence of detectable systemic bacterial translocation (BT), we tested the hypothesis that shock-induced intestinal injury will result in the gut becoming a cytokine-generating organ by measuring interleukin 6 (IL-6) and tumor necrosis factor (TNF) levels in the portal blood, cardiac blood, and intestinal lymph of rats subjected to sham, 30, 60, or 90 min of hemorrhagic shock (30 mm Hg). These blood and lymph samples, as well as the mesenteric lymph nodes (MLN), spleens, and livers, were cultured for translocating bacteria. Although all the portal and cardiac blood samples were sterile, the portal blood levels of TNF and IL-6 were increased to a greater extent than simultaneously obtained cardiac blood samples in rats subjected to 60 or 90 min of shock (p < .05). The lymph IL-6 levels increased but were similar between the groups. BT was limited to the MLN and occurred in a dose-dependent fashion with 38, 63, and 100% of the animals having culture-positive MLNs after 30, 60, or 90 min of shock, respectively. In conclusion, after hemorrhagic shock, the gut appears to become a cytokine liberating organ even in the absence of detectable bacteria in the portal circulation.

Animals↗
PubMed1994

Hemorrhage induces a reduction in the capacity of macrophages to mobilize intracellular calcium secondary to formyl-methionyl-leucyl-phenylalanine stimulation: association with alterations in cells surface Fc receptor expression and increased prostaglandin release.

Studies indicate that simple hemorrhage induces profound suppression in splenic and peritoneal macrophage (Mphi) functions such as antigen presentation, reduced major histocompatibility complex class II antigen expression, as well as cytokine release. Since many of these macrophage functions require the mobilization of [Ca2+]i, our aim was to determine whether or not hemorrhage produced changes in the splenic and/or peritoneal Mphi's ability to mobilize [Ca2+]i. Mphis taken from mice (C3H/HeN) 2 h posthemorrhage (1 h duration; 35 mm Hg), exhibited a significantly reduced capacity to mobilize [Ca2+]i when exposed to formyl-methionyl-leucyl-phenylalanine (FMLP) compared to shams. This loss of the capacity to mobilize [Ca2+]i in response to FMLP stimulation was not due to an inability of Mphis to recruit Ca2+ from extracellular sources. Staurosporine pretreatment ablated the response to FMLP and, since these cells produced less inositol 1,4,5-triphosphate, this indicates that Mphis taken from hemorrhage animals are unable to recruit Ca2+ from intracellular stores. This dysfunction, which was observed following hemorrhage, was associated with the decrease in the number of Fc receptor-positive cells. However, despite this loss, the residual Fc receptor-positive cells present following hemorrhage were capable of releasing enhanced levels of PGE2. It may well be that the residual Fc receptor population represents a sub-population of cells which have been differentially primed for enhanced PGE2 release by the hypotensive insult.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Aggressive fluid resuscitation following intestinal ischemia-reperfusion in immature rats prevents metabolic derangements and down regulates interleukin-6 release.

We have recently shown improved survival following intestinal ischemia-reperfusion in a model that utilized aggressive crystalloid resuscitation sufficient to eliminate reperfusion-induced cardiovascular instability. The aims of this study were to determine whether the salutary effects associated with this regimen were due to: 1) prevention of systemic metabolic derangements; 2) attenuation of secondary organ injury; or 3) modulation of the systemic immune response. Under anesthesia, 4-week-old (65-85 g) male Sprague-Dawley rats (N = 63) received crystalloids at either 15 or 65 ml.kg-1.h-1 intravenously and were subjected to 90 min of superior mesenteric artery occlusion followed by 90 min of reperfusion (IR15, IR65) or time-matched sham (SH) operation (SH15, SH65). Results indicate that inadequate fluid resuscitation following intestinal IR was associated with significant serum hyperkalemia and hyperphosphatemia, acute renal insufficiency, and enhanced serum interleukin-6 levels. Maintenance of cardiovascular stability with aggressive fluid resuscitation was associated with an attenuation of these alterations. Therefore, the prevention of circulatory shock and the attenuation of distant organ injury and inflammatory response are associated with improved survival when an aggressive crystalloid resuscitation regimen is applied after intestinal ischemiareperfusion in immature rats.

Animals↗
PubMed1994

Measurement of circulating blood volume in vivo after trauma-hemorrhage and hemodilution.

Although cardiac output (CO) and other hemodynamic variables are used to assess the adequacy of fluid resuscitation after hemorrhage, it is not known whether there is any correlation between restoration of CO and circulating blood volume (CBV). To determine this, rats underwent a midline laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximum bleedout volume was returned in the form of Ringer lactate (RL). The animals were then resuscitated with four or five times the volume of maximum bleedout in the form of RL. CO and hepatocellular function were measured using an in vivo hemoreflectometer. CBV was monitored by using in vivo indocyanine green clearance. A good correlation between the values of blood volume obtained by this method and the 125I-albumin method indicates that the indocyanine green method is also a reliable technique for measuring CBV. Results indicate that resuscitation after hemorrhage improved the decreased CBV but did not restore it to control levels despite the fact that CO was restored and central venous pressure was more than doubled. A good correlation between depressed CBV and hepatocellular dysfunction was also observed under such conditions. Thus measurement of CBV appears to be useful for evaluating the adequacy of fluid resuscitation after trauma-hemorrhage and hemodilution.

Animals↗
PubMed1994

[Primary cerebral lymphoma following+ kidney transplant: a case report and review of the literature].

We report a 30 year old male, presenting eight years after receiving a kidney transplant with intracranial hypertension and two hyperdense masses detected in a brain CAT scan, whose histopathological study revealed a giant cell immunoblastic lymphoma. The patient was successfully treated with chemo and radiotherapy and after 18 months of follow up there is no evidence of tumoral relapse. Immunocompromised patients, specially transplant recipients, had a several fold higher incidence of malignant tumors, specially primary lymphomas of the central nervous system. These are generally of B type, are associated to Epstein Barr virus and have a high mortality. Cancer must be considered in the differential diagnosis of masses of uncertain origin in transplant recipients.

Adult↗
PubMed1994

[Focal and segmental glomerulosclerosis in renal transplantation].

In 179 patients subjected to 186 renal transplants, 30 renal biopsies were performed due to the presence of a proteinuria over 3.5 g/24 h or due to a reduction in glomerular filtration rate. Six of these biopsies, coming from 5 patients, disclosed morphological alterations compatible with focal segmental glomeruloesclerosis. Five of these were due to recurrence of the primary disease (in four patients) and in all, massive proteinuria appeared from 1 to 23 days after transplantation. Two patients with three transplants, evolved to renal failure and required dialysis in a period 12 months as a mean. The third patient, developed a nephrotic syndrome without renal failure and died 14 months after the renal transplant due to a stroke. In the fourth patient, the nephrotic syndrome disappeared 38 days after the transplant and remained with minimal proteinuria until his last follow up visit two years later. The primary disease of the fifth patient is unknown; the nephrotic syndrome appeared 68 months after the transplant and remitted spontaneously in 2 months. The renal biopsy showed focal and segmental lesions with partial effacement of epithelial foot processes. It is concluded that focal segmental glomerulosclerosis recurrence in renal transplant occurs with early massive proteinuria and frequently leads to renal failure and graft loss in no more than two years.

Adolescent↗
PubMed1994

Peritoneal macrophages show increased cytokine gene expression following haemorrhagic shock.

Tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-1 and transforming growth factor-beta (TGF-beta) have been recognized as important mediators of pathophysiological and immunological events associated with shock. Previous studies have indicated that although peritoneal macrophage (PM phi) antigen presentation was depressed following haemorrhage, the cytokine release capacity in response to lipopolysaccharide (LPS) was not affected in vitro. To determine the effect of haemorrhagic shock on PM phi cytokine mRNA transcription, C3H/HeN male mice were bled to and maintained at a mean arterial blood pressure of 35 mmHg for 60 min, and then adequately resuscitated. PM phi were isolated at 1 or 24 hr after haemorrhage and were incubated without or with 10 micrograms LPS/ml for 1 hr. Total RNA was then extracted followed by Northern blot analysis, as well as semi-quantitative reverse transcription and polymerase chain reaction (RT-PCR). The results of Northern blot analysis indicated that haemorrhage markedly increased LPS-induced IL-1 beta, IL-6, and TNF-alpha mRNA accumulation in PM phi at both 1 and 24 hr after haemorrhage and resuscitation. Furthermore, competitive RT-PCR demonstrated that mRNA of IL-1 beta, IL-6, TNF-alpha, as well as TGF-beta, was increased in PM phi obtained 1 hr after haemorrhage either with or without LPS stimulation. The data from Northern blot analysis and semi-quantitative RT-PCR also revealed that LPS enhanced the effect of haemorrhage on PM phi cytokine gene expression. Thus, following haemorrhage, PM phi showed elevated cytokine mRNA accumulation which was not followed by an increased ability to release cytokines in response to LPS in vitro. These results, therefore, suggest that different mechanisms regulate gene expression and subsequent cytokine secretion by PM phi following haemorrhage.

Animals↗