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Biomedical subjects

Benzion Beilin

Publications and source records attributed to Benzion Beilin.

13 recordsLinked to original sources

The involvement of glucocorticoids and interleukin-1 in the regulation of brain prostaglandin production in response to surgical stress.

BACKGROUND: This study examined the role of glucocorticoids (GC) and interleukin-1 (IL-1) in regulating the production of brain prostaglandin E(2) (PGE(2)) in response to surgical stress. METHODS: Surgical stress was induced in rats by laparotomy or exploration of the carotid. PGE(2) ex vivo production was measured in the frontal cortex or central amygdala of adrenalectomized rats, or of rats treated with either the GC type II receptor blocker (RU38486) or synthetic GC (dexamethasone). IL-1 involvement in mediating PGE(2) response to surgical stress was examined in IL-1 receptor type I deficient (IL-1rKO) mice. RESULTS: Surgical stress elevated serum corticosterone and increased PGE(2) production by the frontal cortex and the central amygdala. A more pronounced PGE(2) response was found in adrenalectomized rats and in rats treated with RU38486, whereas administration of dexamethasone inhibited stress-induced PGE(2) production. IL-1rKO mice exhibited lower PGE(2) production in the frontal cortex under basal condition and failed to increase PGE(2) production in response to surgical stress. CONCLUSIONS: Surgical stress-induced production of brain PGE(2) is specifically regulated by GC via the mediation of type II corticosteroid receptors. Normal IL-1 signaling is required for the production of brain PGE(2) under basal conditions and in response to surgical stress.

Adrenalectomy↗

Blood rheology in PCA and PCEA after total knee arthroplasty.

The rheological events in 2 groups of patients undergoing total knee arthroplasty were compared--15 patients were given general anesthesia and controlled their postoperative pain applying intravenous patient-controlled analgesia; 17 individuals received combined spinal-epidural anesthesia and controlled their postoperative pain by patient-controlled epidural analgesia (PCEA). Twenty-four and 48 hours after surgery, the patient-controlled analgesia group showed a significant increase in whole-blood viscosity at the 3 shear rates (P < .01), as well as in relative viscosity at both periods (P < .001 and .01, respectively). Similar findings were observed for red blood cell aggregation (P < .001) and fibrinogen level (P < .001). These values were less expressed in the PCEA group, particularly 48 hours after surgery (P < .01), and the patients showed lower scores on the visual analog pain scale. The better results observed in the PCEA group favor the application of epidural anesthesia and PCEA analgesia in patients undergoing total knee arthroplasty.

Aged↗

Effects of surgical stress on brain prostaglandin E2 production and on the pituitary-adrenal axis: attenuation by preemptive analgesia and by central amygdala lesion.

Surgical stress is the combined result of tissue injury, anesthesia, and postoperative pain. It is characterized by elevated levels of adrenocorticotropin (ACTH), corticosterone (CS), and elevated levels of prostaglandin E2 (PGE2) in the periphery and in the spinal cord. The present study examined the effects of perioperative pain management in rats undergoing laparotomy on serum levels of ACTH, CS, and on the production of PGE2 in several brain regions, including the amygdala. The amygdala is known to modulate the pituitary-adrenal axis response to stress. We, therefore, also examined the effects of bilateral lesions in the central amygdala (CeA) on laparotomy-induced activation of the pituitary-adrenal axis in rats. In the first experiment, rats either underwent laparotomy or were not operated upon. Half the rats received preemptive analgesia extended postoperatively, the other received saline. ACTH, CS serum levels, and ex vivo brain production of PGE2 were determined. In the second experiment, rats underwent bilateral lesions of the CeA. Ten days later, rats underwent laparotomy, and ACTH and CS serum levels were determined. Laparotomy significantly increased amygdala PGE2 production, and CS and ACTH serum levels. This elevation was markedly attenuated by perioperative analgesia. Bilateral CeA lesions also attenuated the pituitary-adrenal response to surgical stress. The present findings suggest that the amygdala plays a regulatory role in mediating the neuroendocrine response to surgical stress. Effective perioperative analgesia attenuated the surgery-induced activation of pituitary-adrenal axis and PGE2 elevation. The diminished elevation of PGE2 may suggest a mechanism by which pain relief mitigates pituitary-adrenal axis activation.

Adrenal Cortex Hormones↗

Tramadol does not impair the phagocytic capacity of human peripheral blood cells.

PURPOSE: The inhibitory effect of opioids on phagocytic cell capacity is well established. However, the effect of synthetic analgesics on this aspect of cell function is controversial. It was the aim of the study to compare the in vitro effect of tramadol with that of morphine on the engulfing ability of peripheral blood phagocytic cells from healthy volunteers. METHODS: Peripheral blood polymorphonuclear cells and monocytes from healthy volunteers were incubated with 5, 10 and 20 microg.mL(-1) tramadol, or with 20, 40 and 80 etag.mL(-1) morphine. To each tube, 0.05 mL of 5% suspension of latex beads 0.8 microm in diameter was added. After incubation for 60 min the percentage of cells engulfing latex particles and the phagocytic index (number of particles phagocytized by each individual cell) were detected. RESULTS: Tramadol affected neither the percentage of cells phagocyting latex particles, nor the phagocytic index of both polymorphonuclear cells and monocytes. On the other hand, incubation with 20, 40 and 80 etag.mL(-1) morphine caused 11%, 14% and 24% decrease in phagocytosis (P < 0.01 - P < 0.001). The percentage of monocytes phagocyting latex particles was lower by 16%, 19% and 12% at the three doses tested (P < 0.01 - P < 0.001). The three doses of morphine caused a dose dependent decrease in the monocyte phagocyting index by 20%, 29% and 35.5% respectively (P < 0.05). The polymorphonuclear phagocyting index was not significantly lower following incubation with the drug (P = 0.053). CONCLUSION: The lack of noxious effect of tramadol on the engulfing capacity of phagocytic cells suggests additional benefit to the relatively safe profile of the drug.

Analgesics, Opioid↗

General anesthesia for surgery influences melatonin and cortisol levels.

The purpose of this study was to investigate the effect of general anesthesia and surgery on melatonin production, and to assess the relationship between melatonin secretion and cortisol levels. Twenty (9 males and 11 females) consecutive otherwise healthy patients aged 27 to 52 years were included in this study. The patients underwent laparoscopic cholecystectomy or laparoscopic hernioplasty. All patients had general anesthesia with the same anesthetic drugs. Serum cortisol levels were measured at several time periods. Urine collections for melatonin were performed from 18:00 to 7:00 the day prior to surgery, on the operation day, and on the first postoperative day. Baseline melatonin metabolites were measured the night prior to surgery, and the level was found to be 1979 +/- 1.76 ng. The value decreased to 1802 +/- 1.82 ng (NS) on the night of surgery, and it became a significantly higher, reaching 2981 +/- 1.55 ng the night after surgery (p = .003). The baseline daytime cortisol level was significantly lower than the baseline night cortisol level (6.87 +/- 1.51 microg/dl, 14.89 +/- 1.66 micrograms/dl, respectively, p < 0.0001). Surgery induced a significant increase in both day and night cortisol levels. Daytime cortisol levels increased from 6.89 +/- 1.51 microg/dl to 16.90 +/- 1.27microg/dl (p < 0.0001), whereas right levels increased from 14.89 +/- 1.66 microg/dl to 29.20 +/- 1.24 microg/ dl (p <0.0001). The morning after surgery, cortisol levels decreased to 10.16 +/- 1.40 microg/dl, lower than the value obtained on the day of surgery (p < 0.0001). As was true of melatonin, cortisol levels did not reach the pre operative level (p < 0.005). The finding of the current study is that melatonin and cortisol levels show an inverse correlation after surgery.

Adult↗

The effects of perioperative pain management techniques on food consumption and body weight after laparotomy in rats.

UNLABELLED: We examined the effects of two perioperative pain management techniques on recovery after laparotomy, as assessed by body weight (BW) and food consumption (FC). All rats received a preoperative intrathecal mixture of morphine plus bupivacaine combined with one of two treatments: (a) injection of slow-release morphine at the end of the surgery or (b) an antiinflammatory drug, interleukin-1 receptor antagonist (IL-1ra), combined with the preoperative mixture. Laparotomy significantly decreased FC and BW. Both analgesic treatments resulted in a faster recovery of FC and BW. This beneficial effect was more pronounced in the group receiving preoperative analgesics combined with IL-1ra. IMPLICATIONS: Effective perioperative pain management can improve postoperative recovery. We studied the effects of two preoperative pain management techniques on recovery after laparotomy in rats. Both analgesic treatments resulted in a faster recovery, especially preoperative analgesics combined with interleukin-1 receptor antagonist.

Animals↗

Rheological events following laparoscopic and conventional laparotomy.

Laparoscopic surgery has become a widely used procedure with many advantages compared to conventional laparotomy. Although rare, this technique is not entirely absent from clinical hazards and particularly thromboembolic events. This complication is due to activation of the coagulation cascade, as well as factors that may cause alterations in blood rheology. Apart from high hematocrit, presence of abnormal proteins and elevated fibrinogen level, the type of anesthesia, temperature, and increased intra-abdominal pressure following CO(2) insufflation may affect blood viscosity. Therefore, the objective of the study was to compare rheological events in 17 patients undergoing laparoscopic surgery to those in 15 patients who underwent laparotomy. Both groups of patients did not show any complications during the early and late post-operative period. The values of whole blood viscosity in patients undergoing laparoscopy did not differ from those in patients treated by laparotomy. A slight, although significant decrease in plasma viscosity and red blood cell aggregation was observed in patients who underwent laparotomy. The results suggest that the benefits of laparoscopic surgery in the present series were not affected by alterations in blood and plasma viscosity, as well as in red blood cell aggregation.

Blood Viscosity↗

The relationship between partial splenectomy and peripheral leukocyte count.

BACKGROUND: Partial splenectomy is accepted as a treatment modality for hypersplenism permitting preservation of the spleen functions. Since a prominent leukocytosis is a marked event after total splenectomy, it was the aim of the present study to compare the peripheral white blood cell counts (PWBC) and immune response in mice following partial and total splenectomy. MATERIALS AND METHODS: Four groups of animals were included in the study: mice in which 70% of the spleen was removed, animals that underwent total splenectomy, mice with sham operation, and a group of mice that served as controls. The proliferative response of peripheral blood mononuclear cells, peritoneal cells, and splenocytes was examined using concavalin (Con) A. RESULTS: In distinction from marked leukocytosis observed in mice after total splenectomy, in partially splenectomized mice the PWBC counts did not show any significant increase during a follow-up period of up to 2 months after surgery. The mitogen response of the mononuclear cells to Con A in partially splenectomized mice was similar to that of controls, while in animals after total splenectomy, it was increased in cells from the peripheral blood and decreased in those from the peritoneum. CONCLUSIONS: The results indicate that removal of as much as about 70% of the spleen in mice is sufficient to maintain a normal PWBC count, suggesting a regulatory role of the spleen remnant on the PWBC production. The normal mitogen response of the cells to Con A indicates that the spleen rudiment preserves at least a part of the immune activity of the intact spleen.

Animals↗

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.

Adenocarcinoma↗

Effects of preemptive analgesia on pain and cytokine production in the postoperative period.

BACKGROUND: The postoperative period is associated with increased production of proinflammatory cytokines, which are known to augment pain sensitivity, among other effects. In a previous study, the authors found that patients treated with patient-controlled epidural analgesia (PCEA) exhibited attenuated proinflammatory cytokine response in the postoperative period. In the present study, the authors examined whether preemptive analgesia continued with PCEA may further attenuate the proinflammatory cytokine response and reduce pain sensitivity in the postoperative period. They compared cytokine production in two groups of patients, one receiving PCEA, the other receiving preemptive epidural analgesia continued by PCEA. METHODS: Female patients hospitalized for transabdominal hysterectomy were randomly assigned to one of two pain management techniques: PCEA or preemptive epidural analgesia followed by PCEA (PA + PCEA). Postoperative pain was assessed using the visual analog scale. Blood samples were collected before, 24, 48, and 72 h following surgery. Production of the following cytokines was assessed in stimulated peripheral blood mononuclear cells: interleukin (IL)-1beta, tumor necrosis factor alpha, IL-6, IL-1ra, IL-10, and IL-2. RESULTS: Patients of the PA + PCEA group exhibited lower pain scores throughout the 72 h postoperatively, compared with patients of the PCEA group. In patients of the PA + PCEA group in the postoperative period, production of IL-1beta, IL-6, IL-1ra, and IL-10 was significantly less elevated, while IL-2 production was significantly less suppressed. CONCLUSIONS: Proinflammatory cytokines are key mediators of illness symptoms, including hyperalgesia. The present results suggest that preemptive epidural analgesia is associated with reduced postoperative pain and attenuated production of proinflammatory cytokines.

Adult↗

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.

Adult↗

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.

Animals↗

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.

Animals↗