Effect of a BIOcocktail on the immune response at the early postoperative period in mice.

Since human subjects and laboratory animals may develop impaired immune response during surgery and the postoperative period, efforts have been made to preserve normal immune functions following surgery by the administration of nutritional supplements and probiotics. The present study was designed to examine the effect of a new nutritional supplement, BIOcocktail, on immune parameters in mice exposed to surgery. Forty mice were assigned to 4 groups containing 10 animals each. Two control groups (with and without subsequent sham laparotomy) were given tap water for 45 min every day for 2 weeks. The remaining 2 groups, with and without laparotomy, received BIOcocktail given orally for the same period of time. The proliferative response of splenic cells (splenocytes) stimulated with phytohemagglutinin (PHA), concanavalin A (Con A) and lipopolysaccharide (LPS) was determined by [3H]thymidine uptake. Cytokine levels were measured in splenocyte supernatants and sera using enzyme-linked immunosorbent assay (ELISA) kits. Natural killer cell activity of splenocytes was evaluated by 51Cr-release assay. Laparotomy, without BIOcocktail administration, was followed by a decreased proliferative response of splenocytes to PHA, Con A, and LPS and an increase in interleukin (IL)-6 serum level. In addition, a decreased secretion of IL-1beta, IL-12 and tumor necrosis factor (TNF)-alpha by the splenocytes was observed. Mice treated with BIOcocktail before laparotomy maintained a preoperative level of splenocyte proliferative response and serum concentrations of IL-12. It is concluded that BIOcocktail administered to mice for 2 weeks before operation resulted in the preservation of T- and B-cell proliferative response to mitogens and in the prevention of postoperative decrease in IL-12 serum level.

Effects of fentanyl on natural killer cell activity and on resistance to tumor metastasis in rats. Dose and timing study.

OBJECTIVES: Opiates, which serve an integral role in anesthesia, suppress immune function, particularly natural killer cell cytotoxicity (NKCC). NK cells play an important role in tumor and metastasis surveillance. We reported that large-dose fentanyl anesthesia induced prolonged suppression of NKCC in patients undergoing abdominal surgery. The immune modulatory effects of opiates may depend on the interaction between dose and time of administration. The present study examined the effects of different doses of fentanyl, administered at different time points relative to tumor inoculation, on NKCC and on experimental tumor metastasis in rats. METHODS: Fischer 344 rats were injected with low or high doses of fentanyl, 6 or 2 h before, simultaneously with or 1 h after being inoculated intravenously with MADB106 tumor cells. Lung tumor retention (LTR) was assessed 4 h after, and lung tumor metastases were counted 3 weeks after tumor inoculation. NKCC was assessed 1 h after the fentanyl injection. RESULTS: At all time points, except 6 h before tumor inoculation, fentanyl (0.1-0.3 mg/kg) induced a dose-dependent increase in MADB106 LTR (2.3- to 74-fold). An intermediate dose of fentanyl (0.15 mg/kg) doubled the number of lung metastasis, and, within animal, suppressed NKCC and increased MADB106 LTR in a correlated manner. CONCLUSION: These findings indicate that fentanyl suppresses NKCC and increases the risk of tumor metastasis. Suppression of NK cells at a time when surgery may induce tumor dissemination can prove to be critical to the spread of metastases. It is suggested that the acute administration of a moderate dose of opiates during surgery should be applied cautiously, particularly in cancer patients.

The effects of postoperative pain management on immune response to surgery.

Surgery is associated with immune alterations, which are the combined result of tissue damage, anesthesia, postoperative pain, and psychological stress. In the present study, we compared the effects of several postoperative pain management techniques on postoperative immune function. Patients hospitalized for abdominal surgery were randomly assigned to one of three postoperative pain management techniques: opiates on demand (intermittent opiate regimen [IOR]), patient-controlled analgesia (PCA), and patient-controlled epidural analgesia (PCEA). Postoperative pain was assessed. Blood samples were collected before and 24, 48, and 72 h after surgery. Production of interleukin (IL)-1beta, IL-2, and IL-6, natural killer cell cytotoxicity, and lymphocyte mitogenic responses were assessed. Patients of the PCEA group exhibited lower pain scores in the first 24 h after surgery compared with patients of the IOR and PCA groups. Mitogenic responses were suppressed in all groups in the first 24 h, returned to preoperative values by 72 h in the PCEA group, but remained suppressed in the PCA group. Production of IL-1beta and IL-6 increased in the IOR and PCA groups, whereas it remained almost unchanged in the PCEA group. Patients receiving an epidural mixture of opiate and local anesthetics (PCEA group) exhibited reduced suppression of lymphocyte proliferation and attenuated proinflammatory cytokine response in the postoperative period.

Tc99m macroaggregated albumin cisternography for the detection of persistent cerebrospinal fluid (CSF) leak in an animal model.

The present study describes a new in vivo animal model that enables the detection of cerebrospinal fluid (CSF) leakage after dural injury. A polyethylene catheter (PE 10) was inserted into the subarachnoid space in the lumbar area by a simple surgical procedure and a radioactive isotope Tc99m Macroaggregated Albumin (Tc99m MAA) was injected into the CSF. In the experimental group, a standardised dural puncture was performed in the cervical area. The accumulation of the isotope in the gauze placed over the dural puncture and viewed by a gamma camera as a spot of concentrated radioactivity, was indicative of CSF leakage. In a second group of animals with intact cervical dura the absence of leakage was presented as a picture of sporadic background radioactivity. To demonstrate the effectiveness of the model in detection of invisible leakage, blood was applied over the cervical dural defect in another group of animals and CSF leakage was assessed by the above mentioned isotope detection method. This in vivo model may be used for evaluation of the sealing properties of various materials under physiological and metabolic processes in living tissue.