Pharmacological immunomodulation of surgical trauma.

Surgery and accidental trauma induce changes in the immune response, showing a predominant pattern of activation through the Th2 cell pathway to the detriment of Th1 cell pathway activation. Anapsos is a hydrosoluble extract obtained from Polypodium leucotomos. Anapsos has shown immunomodulating effects in vitro. On a rat experimental model (tibia and fibula fracture), cytokines (interleukin [IL]-2, IL-4, IL-6, IL-10, and IL-12) (enzyme-linked immunosorbent assay, ELISA) and cell percentages of CD4, CD8 CD25, CD122, and CD132 (monoclonal antibodies, MoAb) were determined in peripheral blood 7 days before surgery (PRE), 1 day after surgery (1PO), and 7 days after surgery (7PO). On postoperative day 1, rats undergoing fracture show an increase of CD8 percent expression and IL-6 and IL-10 levels, in contrast to rats undergoing fracture plus anapsos treatment. On postoperative day 7, rats undergoing fracture show an increase of IL-6 levels, whereas rats undergoing fracture plus anapsos do not. The IL-12 level decreases on postoperative day 7 in the group with fracture but not in the fracture plus anapsos group. Thus, we conclude that anapsos is able to modulate the immune response after trauma, inhibiting Th2 pathway activation with no effect on Th1 pathway activation. In trauma, Anapsos could prevent the shifting Th1/Th2 balance.

Apoptosis and CD8 and CD54 cell expression in rat small bowel transplantation.

The importance of activated CD8 cells expressing IL-2R in small bowel and other organ rejection has been reported. Some authors even consider that a positive correlation might be demonstrated between the number of apoptotic enterocytes and the degree of graft rejection. In addition, moderate to intense activation of endothelial molecules in small bowel allograft in rats has been reported in chronic rejection. The aim of the present paper is to ascertain, in a heterotopic small bowel transplantation (HSBT) in rats, whether CD3, CD4, CD8, and CD54 cell expression in the allograft infiltrates shows some relationship with allograft enterocyte apoptosis when rejection is present. Wistar Furth male rats were allotted to two groups: group A was the control group without transplantation; group B received a heterotopic small bowel allograft from Fisher rats and an im dose of FK506 (0.25 mg/kg/day). A significant increase of CD8, CD54 cell receptor expression, and apoptosis in the group undergoing HSBT showed rejection. No significant differences have been observed in the variables under study between the control and HSBT without rejection groups or in CD3 and CD4 among the three groups. We observed a significant correlation between apoptosis and rejection, between CD8 and CD54 with apoptosis and with rejection, and between CD8 and CD54. This indicates that the activation of endothelial molecules and cells may play an important role in established HSBT chronic rejection. We consider that this study may contribute to the knowledge of small bowel allograft chronic rejection and its immunomodulation.

Determination of the immunoglobulin E postoperative variation as a measure of surgical injury.

The aim of this study was to ascertain postoperative changes in immunoglobulin E (IgE) in patients undergoing different types of surgery and the possible correlation with the duration and type of surgery. Evidence suggests that surgery induces a predominant activation pattern through the T-helper-2 (Th2) cell pathway, increasing interleukins (IL-4, IL-5, IL-10, IL-13), inhibiting Th1 cell activation, and promoting B and Th2 cell activation. IgE production may indicate predominant Th2 pathway activation and may be a more persistent and easily measurable postoperative marker than IL-6 for measuring surgical trauma. Altogether, 180 patients undergoing different types of surgery for nonneoplastic and nonparasitic diseases were studied. All patients received the same type of anesthesia. Before surgery and on the first (1PO) and 7th (7PO) postoperative days we determined in peripheral blood the CD3, CD4, CD8, CD16, and CD19 cell percentages; IL-1, IL-2, IL-4, IL-6, and tumor necrosis factor (TNF) levels; and the IgA, IgG, IgM, total IgE, C3, C4, and CIC levels. On 1PO, all variables decreased except IgE, IL-1, IL-2, IL-4, IL-6, CIC, and CD19. Only IgE, IL-6, and CD19 increases showed a significantly statistical (ss) difference regarding preoperative values (0.01, 0.05, 0.001, respectively). Relations between the IL-4 and IgE increases (p < 0.01) and between the IgG decrease and IgE increase (p < 0.001) were found. On 7PO, only IgE was increased (p < 0.001). The IgE increase correlated with surgical trauma intensity (p < 0.05). We concluded that IgE increases during the early postoperative period, correlating with surgical injury intensity. The increase in the IgE level may be detected 24 hours after surgery and during the first 7 postoperative days depending on the type of surgery.

Diaphragm disease of the small bowel: a case without apparent nonsteroidal antiinflammatory drug use.

BACKGROUND: Diaphragm-like strictures of the small bowel are an infrequent complication of the treatment of patients with nonsteroidal antiinflammatory drugs (NSAIDs). STUDY: We report a patient with this condition in whom the use of NSAIDs was ruled out by both clinical history and objective blood testing of current aspirin use. RESULTS: He reported a history of recurrent episodes of colic abdominal pain during the past 25 years; he underwent three surgical operations for this condition. Before these symptoms, he had an undefined abdominal process with diarrhea, weight loss, and diffuse edema, which resolved spontaneously without reaching a diagnosis. CONCLUSIONS: We suggest that diaphragm-like strictures might be developed as a nonspecific response to different damaging insults to the intestine and are not necessarily associated with NSAID use.

Intracystic infection of liver hydatidosis.

BACKGROUNDS/AIMS: The aim of this study was to review the clinical presentation and management of patients with intracystic bacterial infection in liver hydatidosis. METHODOLOGY: The records of 480 patients suffering from liver hydatid disease treated at our institution were reviewed. Only 42 patients fulfilled intracystic bacterial infection criteria. We assessed the incidence, clinical and laboratory findings, diagnostic procedures and surgical approach in these cases. RESULTS: The incidence of intracystic bacterial infection was steady throughout the study period. Clinical and laboratory data are non-specific. Diagnostic procedures for intracystic bacterial infection, including liver computed tomography scan, are of limited value. Although both, radical and non-radical surgical approaches, were used in these patients, mortality was associated with non-radical surgery. The morbidity rate was high regardless of the procedure used. CONCLUSIONS: Our current goal in the management of intracystic bacterial infection, if overall condition of the patient is good, is to carry out a total or subtotal cystectomy in order to avoid mortality and hydatid disease relapses.

Autologous blood transfusion as an immunomodulator in experimental sepsis.

BACKGROUND: Homologous blood transfusion is associated with immunosuppressive consequences. Some clinical and experimental studies have suggested an immunostimulating action of autologous blood transfusion. The aim of this paper is to ascertain the effects of either homologous blood transfusion or autologous blood transfusion on the lymphocyte subsets and cytokines in a model of intra-abdominal sepsis. MATERIALS AND METHODS: There were three study groups. Group A: 10 Wistar-Furth (WF) rats underwent cecal ligation and puncture (CLP) aimed at causing an intra-abdomial sepsis; Group B: 10 WF rats underwent CLP plus 1 ml homologous blood perioperative transfusion obtained from Fisher-344 rat while Group C: 10 WF rats underwent CLP plus 1 ml autologous blood perioperative transfusion. Changes of peripheral lymphocyte subsets, percentages of total T-lymphocytes (CD3), Helper T-lymphocytes (CD4), supressor/cytotoxic T-lymphocytes (CD8), CD4/CD8 ratio, Interleukin-2 receptor expression (IL-2R) and cytokines IL-1 and TNF-alpha were measured in peripheral blood on the preoperative, 1st, 3rd and 7th postsepsis (PO) days. RESULTS: Rats in homologous transfused group showed a decrease of %CD4 on the 3rd PO (from preoperative to 3rd PO;p < 0.01; and from 1st to 3rd PO; p < 0.05) and on the 7th PO (from preoperative to 7th PO; p < 0.05); %CD8 increased from preoperative to 3rd PO (p < 0.05), from 1st to 3rd PO (p < 0.01) and from 1st to 7th PO (p < 0.05). An initial decrease on day 1 (p < 0.01) followed by an increase on the 3rd PO (p < 0.01) with regard to IL-2R and a significant increase of IL-1 levels within the first 24h (p < 0.01). Rats in autologous transfused group showed an increase of %CD3 from preoperative to 7th PO (p < 0.05), and from 3rd to 7th PO (p < 0.01). CONCLUSIONS: We observed that homologous blood transfusions induce a greater alteration in the cellular immune response and of the cascade of cytokines than autologous transfusions. This modulates the variations of the immune response induced by sepsis.

S-adenosylmethionine immunomodulator treatment in sepsis.

BACKGROUND: S-adenosylmethionine (SAMe) is a forerunner of glutathione. AIMS: The aim of the present study is to ascertain this drug effect on T-lymphocytes and cytokines in an experimental model of surgical sepsis. METHODS: Rats were allotted in two groups. In the control group, rats underwent anaesthesia and laparatomy with cecal ligation and puncture (CLP). In the second group, rats underwent the same CLP and received SAMe (14 mg/kg) i.m., on the 1st (1PO) and 2nd (2PO) postoperative days. A week before surgery (PRE), on the 1PO and on the 3PO: IL-1, IL-2, IL-4, IL-6, IL-10 and TNF levels (ELISA & MoAb), and CD3, CD4, CD8 cell and IL-2R percentages (%) (flow cytometry & MoAb) were determined in peripheral blood. RESULTS: Rats receiving SAMe do not show changes of CD3%, CD4% and IL-1 levels but show a significant increase of CD8% on the 3PO, showing a significant difference with regard to controls (p < 0.01). Both groups show a similar IL-2R variation pattern: increasing on 1PO (p < 0.05) and decreasing on 3PO (p < 0.05). CONCLUSION: In sepsis: SAMe inhibits the decrease of circulating immune-active cells and the IL-1 increase. This drug seems to have effects useful in avoiding immunological alterations in sepsis, that need to be tested in humans.

Primary hydatid disease in lumbar muscles.

The authors report a case of primary hydatid disease in the lumbar muscles of a 40-year-old male patient. The rarity of this disease in our regions and the low incidence of this location make primary diagnosis difficult. The tumor had been treated elsewhere five years previously by means of simple excision. Recurrence of the lesion was diagnosed five years after the first surgery. Wide excision of the cyst and pericyst with a 3.5-cm security margin was performed. Six years after the last surgery, no recurrence has been detected.

Immune response and cytokines in septic rats undergoing blood transfusion.

BACKGROUND: Intrabdominal sepsis and allogeneic blood transfusion have been associated with a depression of the immune response in patients undergoing surgery. Some authors have considered that an already immunocompromised host is probably primed for a potential detrimental effect of allogeneic blood. The aim of this paper is to ascertain the effects of allogeneic blood transfusion on the lymphocyte subsets and cytokines in septic rats. MATERIALS AND METHODS: Thirty rats were allotted into three groups: Sham-CLP, anesthesia and laparotomy; CLP, cecal ligation and puncture; CLP+BT, CLP and allogeneic blood transfusion. Preoperatively and on the 1st, 3rd, and 7th postoperative days, the cell percentages of lymphocyte subpopulations, the IL-2 receptor expression, and the IL-1, IL-2, TNF-alpha and IFN-gamma were measured in blood by flow cytometry and ELISA: RESULTS: CLP+BT rats showed on Day 3 a decrease of the CD4+%, an increase of the IL-2R expression directly correlated to the increase of the CD8+% phenotype, a steady increase of IL-1 levels, a decrease of the TNF-alpha levels on the 1st and 3rd days, and a decrease of the IL-2 and IFN-gamma on Day 1. CONCLUSIONS: An accumulative effect of the immunodepression induced by sepsis was observed when allogeneic blood transfusion is added. Blood transfusion + sepsis induces an extensive impairment on cellular immune response and an initial cytokine downregulation, except for IL-1.

Immune response and in vivo production of cytokines in patients with liver hydatidosis.

Cytokines play an important role in the human immunological response, but the exact role of cytokines in the human immune response against parasites, especially against Echinococcus granulosus, remains unclear. IL-1, IL-2, IL-4 and tumour necrosis factor (TNF) levels in peripheral blood of 21 patients with liver hydatidosis were evaluated before surgical treatment, and the levels of IgA, IgM, IgG, IgE, specific IgE against E. granulosus, C3, C4 and DF complement fractions and CD20, CD3, CD4, CD8 and CD16 cell percentages were also determined, as was the relationship between these variables and cytokine levels. Data from hydatid patients were compared with data obtained from 21 healthy volunteers. Hydatid patients showed increases of IgG, IgE, IgEs and IL-2 (P < 0.01), and decreases of IL-1 and TNF levels (P < 0.001), but these variables (respectively) increased in patients showing cysts in the central area of the liver or with a wide opening of cysts in the biliary tract. The increase of IL-1, IL-2 and IL-4 showed a close relationship with the number, characteristics and above all the location of cysts within the liver itself. IgG and IL-4 levels and also IgG and IgE levels showed a significant correlation (P < 0.05).

Changes in blood lymphocyte populations in experimental bowel allograft rejection.

The aim of this study is to measure percentages of lymphocyte populations and IL-2R cellular expression in peripheral blood during the rejection of a small bowel allograft (SBA) in the rat. Thirty rats were allotted to three groups: A, control, no transplantation (Tx); B, rats receiving an orthotopic SBA; C, similar SBA but with thymostimulin (TP-1) administered before Tx, aimed at increasing the intensity of and accelerating rejection. The percentages of CD19, CD5, CD4 and CD8 cells and of IL-2R were determined when rejection was present. Rejection appeared in rats in group B between days 11 and 26 post-Tx and in group C between days 6 and 7 post-Tx (P < 0.001). In both B and C groups, CD5 and CD4 cells decreased (P < 0.005) and CD8 cells increased (P < 0.001). A correlation between CD8 and IL-2R content was found (P < 0.05). In group C, earliness of rejection correlated with the percentage of CD8 cells (P < 0.05) and the intensity of rejection with numbers of CD8 and CD19 cells (P < 0.05).

[Multiple hepatic-splenic abscesses. A favorable result with antibiotic treatment]. / Absceso hepato-esplénico múltiple. Resultado favorable con tratamiento antibiótico.

The authors report a case of multiple and spleen pyogenic abscesses caused by Peptostreptococcus spp., in a patient who recently underwent laparotomy due to duodenal perforation. He was successfully treated by means of intensive and extended antibiotherapy. We would like to stress the importance of an early and etiological diagnosis performed by percutaneous puncture and bacteriological study, in order to start a selective antibiotherapy. Other therapeutical possibilities are discussed.

Immunorestorative effect of thymostimulin on surgery immunodepression: experimental model.

The purpose of the present study is to ascertain the immunorestorative effect of two different drugs on immunodepression induced by small bowel surgical resection in an experimental model. The potential immunorestorative effect has been measured by the ability of the drug to avoid the delay of skin allograft rejection induced by surgery and the inhibition of CD4/CD8 index changes induced by surgery in spleen tissue. 120 Wistar-Furth rats (age 12-16 weeks) anesthetized with a single intramuscular dose of ketamine (25 mg), diazepine (4 mg) and atropine (0.1 mg) were allotted to two main groups. One group received a skin graft (SG) from Fisher 344 rats and was treated with placebo, Inmunoferón (AM-3 polypeptidic drug) or TP-1 (thymostimulin) before the experiment (groups I, II, III) or treated with placebo, Inmunoferón or TP-1 before the experiment and underwent enterectomy and anastomosis (groups IV, V, VI). On the 2nd, 5th and 8th postoperative days, biopsies of the SG were taken and the signs of rejection were microscopically studied and evaluated by a pathologist as zero, incipient, moderate or massive. The other group was treated similarly, but the animals did not receive a SG and were splenectomized 5 days later. CD4 and CD8 lymphocyte subpopulations were identified by means of immunoperoxidase technique and monoclonal antibodies. Thymostimulin is able to stimulate the presence of SG rejection signs on the 2nd postoperative day in nonenterectomized animals and on the 8th postoperative day in nonenterectomized animals and on the 8th postoperative day in enterectomized rats and is able to avoid the decrease of the CD4/CD8 index in spleen tissue after surgical immunodepression.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia and immunosuppression in an experimental model.

The purpose of the present work was to study: (1) if anesthesia induces changes in the helper/cytotoxic/suppressor T cell ratio in the rat spleen, and (2) if there is any difference between two anesthetic methods usually employed in rat experimentation. 50 Fisher 344 rats were allotted into 5 groups. In group A (control), a splenectomy was performed in an average time of 3 min under ether anesthesia. In groups B1 and B2, the rats anesthetized for 1 h with ether (group B1) or with one single dose of ketamine + atropine + diazepam (group B2) and then underwent splenectomy. Groups C1 and C2 were similar to groups B1 and B2 but splenectomy was performed 24 h later, under ether anesthesia during 3 min. T helper (Th) and T cytotoxic-suppressor (Ts-c) cells were identified in periarterial and follicular spleen tissue by means of an immunohistologic analysis using an immunoperoxidase technique with monoclonal antibodies. In periarterial tissue the Th/Ts-c ratio (mean +/- SE) was: group A, 1.61 +/- 0.11; group B1, 1.10 +/- 0.1; group B2, 1.28 +/- 0.11; group C1, 0.85 +/- 0.08, and group C2, 1.23 +/- 0.12. The differences between groups A and B1, C1 and C2 were statistically significant (t = 2.2833) as well as the difference between groups C1 and C2 (t = 2.5223). The Th/Ts-c ratio was also compared when equal to 1 or less than 1. The difference between groups A and C1 was statistically significant (p less than 0.05) as well. In follicular tissue the ratio was 1 in all the groups.(ABSTRACT TRUNCATED AT 250 WORDS)