Intraperitoneal Normal Saline Research Articles

Effect of propofol on ketamine-induced cerebral injury in neonatal rats

Objective To investigate the effect of propofol on the cerebral injury induced by ketamine in neonatal rats. Methods Eighty 7-day-old SD rats of both sexes, weighing 12-20 g, were randomly divided into 4 groups (n = 20 each): normal saline (NS) group, ketamine-induced cerebral injury group (group K), propofol group (group P) and propofol combined with ketamine group (group PK). Group NS received intraperitoneal NS 1 ml. In groups K, P and PK, ketamine 70 mg/kg, propofol 70 mg/kg and propofol 70 mg/kg + ketamine 70 mg/kg were injected intraperitoneally once every 2 h for 3 times respectively. Ten rats in each group were selected and sacrificed at 24 h after emergence from anesthesia and the hippocampi obtained to determine the neuronal apoptosis (by TUNEL) and Bcl-2 and Bax protein expression(by immunohitochemistry). The apoptosis rate was calculated.The other 10 rats in each group were selected at 21 days after the intraperitoneal injection and the learning and memory functions (escape latency and frequency of crossing the original platform) were evaluated using Morris water maze. Results Compared with group NS, the apoptosis rate was significantly increased in group K, Bcl-2 protein expression was up-regulated in groups P and PK, and Bax protein expression was up-regulated, the escape latency was significantly prolonged and the frequency of crossing the original platform was significantly decreased in the other groups (P ＜ 0.05 .or 0.01 ). Compared with group K, the apoptosis rate was significantly decreased in group PK, Bax protein expression was down-regulated in group P, and Bcl-2 protein expression was up-regulated,the escape latency was significantly shortened and the frequency of crossing the original platform was significantlyincreased in groups P and PK ( P ＜ 0.05). Conclusion Propofol can reduce the cerebral injury induced by ketamine in neonatal rats, and the regulation of the Bcl-2 and Bax protein expression and inhibition of the neuronal apoptosis in hippocampus may be involved in the mechanism. Key words: Propofol; Ketamine; Cognition; Hippocampus; Apoptosis

Role of cyclooxygenase-2 and mitochondrial KATP channels in sufentanil preconditioning-induced delayed cardioprotection against myocardial ischemia-reperfusion injury in rats

Objective To investigate the role of cyclooxygenase-2(COX-2)and mitochondrial adenosine tuiphosphate sensitive potassium channels (mito-KATP channels) in sufentanil preconditioning-induced delayed cardiopreteetion against myocardial ischemia-reperfnsion (I/R) injury in rats. Methods Seventy-two adult male Wistsr rats weighing 250-300 g were randomly divided into 6 groups ( n =12 each). Group Ⅰ,Ⅱ,Ⅲ were preconditioned with intraperitoneal (IP) normal saline (NS) 1 ml/kg while group Ⅳ,Ⅴ,Ⅵ with IP sufentanil 20 μg/kg at 24 h before myocardial ischemia. Group Ⅱ and Ⅴ were given IP NS-398 ( COX-2 inhibitor) 5 mg/kg at 30 rain before myocardial ischemla while group Ⅲ and Ⅵ were given intravenous 5-HD (mito-KATP channelblocker) 10 mg/kg at 10 min before ischemia or before being killed. Six animals in each group underwent 45 min myocardial ischemia followed by 120 min reperfusion, while the other six animals in each group were killed immediately before ischemia for determination of myocardial COX-2 expression and myocardial PGF2 and PGF1α content. Myocardial ischemia was induced by occlusion of left anterior descending branch (LAD) of coronary artety for 45 rain followed by 120 min reperfusion. MAP and HR were recorded immediately before ischemia (T0), at 15, 30, 45 rain of ischemia (T1-3) and at 30, 60, 90, 120 vain of reperfusion (T4-7). Heart rate-blood pressure product (RPP) was calculated. Arterial blood samples were obtained at T0.3 and T7 for measurement of plasma CK-MB activity. The animals were killed at the end of 120 nan reperfusion. The hearts were removed for determination of myocardial infarct area (IA) and area at risk (AAR). LA/AAR was calculated. Results There was no significant difference in HR, MAP and RPP at all time points among the 6 groups. Preconditioning with sufentanil significantly decreased plasma CK-MB activity at T3 and T7 and IA/AAR in group Ⅳ as compared with group Ⅰ.Myocardial COX-2 expression was up-regulated and PGE2 and PGF1α, contents were elevated by sufentanil preconditioning in group Ⅳ as eomared with control group (Ⅰ). In group Ⅴ and Ⅳ preconditioning with NS-398/5-HD significantly increased plasma CK-MB concentration and IS/AAB as compared with group Ⅳ, indicating involvement of COX-2 and mito-KATP channels in the sufentanil-induced delayed cardioprotection.The myocardial PGE2 and PGF1α contents were significantly reduced in group Ⅴ as compared with group Ⅳ. There was no significant difference in the myocardial COX-2 expression among group Ⅳ, Ⅴ and Ⅵ. Conclusion Both COX-2 and mito-KATP channels are involved in sufentanil preconditioning-induced delayed cardiopmtection. Key words: Prostaglandin-endoperoxide synthases; KATP channels; Sufentanil; Ischemic preconditioning, myocardial; Myocardial reperfuaion injury

An Evaluation of Influence of Citrus paradisi Seed Extract on Doxorubicin-Induced Testicular Oxidative Stress and Impaired Spermatogenesis

The therapeutic value of Doxorubicin (DOX) as anticancer antibiotic is limited by its organotoxicity. It has been shown that free radicals are involved in doxorubicin-induced toxicity. Doxorubicin causes the generation of free radicals and the induction of oxidative stress, associated with cellular injury. Because of the great importance of DOX in cancer therapy, researchers have expended great efforts trying to prevent or attenuate the side effects of DOX administration. There has, however, been only a little success in this regard. In this study the ameliorating role of antioxidant-rich ethanolic seed extract of Citrus paradisi (CP) on DOX-induced testicular oxidative stress and impaired sperm parameters was investigated. Three experimental groups of Wistar rats were used; CP-alone group that received orally CP 10 mg kg -1 b.wt. daily for 14 days followed by intraperitoneal (i.p.) Normal Saline (NS) 2.5 mg kg -1 b.wt. DOX-alone group that had ip DOX 10 mg kg -1 b.wt. as a single dose. CP plus DOX-group that were similarly given DOX, but also had oral CP 10 mg kg -1 b.wt. pretreatment for 14 days. There was also a corresponding control group. The animals were autopsied 8 weeks after DOX or NS injections. Results showed that DOXinduced reduction in sperm motility and epididymal sperm concentrations as well as increase in total abnormal sperm rates were all normalized in the group pretreated with CP. Pretreatment with CP ameliorated the testicular content of Glutathione (GSH) and Auperoxide Dismutase (SOD), Catalase (CAT) and Glutathione Peroxidase (GPx) activities. Similarly, CP treatment attenuated the DOX-induced increase in testicular lipid peroxidation reflected by malondialdehyde (MDA) levels. These data indicate that CP protects the rat testis against DOX-induced oxidative stress and deranged sperm characteristics.

Low‐dose dexamethasone alleviates lipopolysaccharide‐induced acute lung injury in rats and upregulates pulmonary glucocorticoid receptors

The major causes of mortality among patients who survive acute lung injury/ARDS (ALI/ARDS) are due to the extensive tissue remodelling and fibrosis. Use of high-dose glucocorticoids to reduce these inflammatory and fibroproliferative responses has been shown to do more harm than good. Recently, Meduri et al. found that the early use of low-dose prolonged methylprednisolone in patients with severe ALI/ARDS significantly relieved the systemic inflammatory response and improved pulmonary and extrapulmonary organ function. This study investigated the therapeutic effect of low-dose dexamethasone (Dex) on inflammation and fibrosis in LPS-induced ALI in rats and its influence on the expression of the pulmonary glucocorticoid receptor (GR). Eighty Wistar rats were randomly divided into four groups: a control group (intraperitoneal normal saline injection (5 mL/kg) throughout experiment, n = 24); the LPS model group (LPS injection (5 mg/kg) for 3 days and normal saline thereafter, n = 24); the LPS + Dex group (LPS injection for 3 days and Dex solution (5 mg/kg) thereafter, n = 16); and the Dex group (normal saline injection (5 mL/kg) for 3 days and Dex solution (5 mg/kg) thereafter, n = 16). Levels of tumor necrosis factor-alpha, matrix metallopeptidase-9 and procollagen N-terminal propeptide type I in BAL fluid were examined by ELISA on the third, seventh and fourteenth days after injection. Pulmonary hydroxyproline content was measured and histological examination was performed with haematoxylin-eosin and Victoria blue-ponceau. Pulmonary distribution of GR-positive cells was examined immunohistochemically, and expression of GR mRNA and protein was determined by RT-PCR and western blot analysis. Histological assessments showed that pulmonary fibrosis occurred in parallel with inflammation in the rat ALI model. Compared with the LPS group, the inflammation and fibrosis parameters were significantly improved in the LPS + Dex group at different periods after injection (P < 0.05 or P < 0.01), although parameters in the LPS + Dex group were not as good as those of the control group. GR mRNA and protein expression in the LPS + Dex group were markedly higher than that of the LPS group on the seventh and the fourteenth days (both P < 0.01). Western blotting showed that Dex also promoted the nuclear translocation of GR protein. Low-dose Dex can reduce pulmonary inflammation and fibrosis after LPS-induced ALI in rats and can elevate GR expression in the lung, probably through upregulating GR levels and promoting the nuclear translocation of GR protein.

Administração intraperitoneal da mistura com excesso enantiomérico de 50% de bupivacaína (S75-R25) para analgesia pós-operatória em colecistectomias videolaparoscópicas

The analgesic effect of intraperitoneal administration of local anesthetics after laparoscopic cholecystectomy is a controversial issue, and the results described vary from considerable pain relief to little reduction in pain. The objective of this study was to evaluate the efficacy of the intraperitoneal administration of 50% enantiomeric excess bupivacaine (S75-R25) for the postoperative pain relief of laparoscopic cholecystectomy. A randomized, double blind, placebo controlled study was conducted with 40 patients undergoing laparoscopic cholecystectomy, who were divided in two groups: GI (n = 20) received 80 mL of intraperitoneal 0,125% S75-R25 bupivacaine at the end of the procedure; and GII (n = 20) received 80 mL of intraperitoneal normal saline. Both groups received 40 mg of tenoxicam and 30 mg.kg-1 of intravenous dypirone shortly before the end of the surgery. Tramadol was used for postoperative analgesia (PO). Pain scores were evaluated at rest, sitting up, and during the Valsalva maneuver, according to a numeric scale upon waking up and 2, 4, 8, 12, and 24 hours postoperatively; the presence of shoulder pain was assessed, as well as the length of time until the first request of analgesic and its cumulative consumption. There was a statistically significant difference in resting pain scores at 12 hours PO (GI < GII). The length of time until the first request of tramadol was greater in GI and this group presented smaller consumption of this drug, but these differences were not statistically significant. The intraperitoneal instillation of 80 mL of 0.125% S75-R25 bupivacaine provided for lower resting pain scores, which was statistically significant only at the 12th postoperative hour.

Effect of Interleukin‐10 on Tissue Damage Caused by Organophosphate Poisoning*

Organophosphate poisoning is a common cause of severe morbidity and mortality among patients admitted to emergency departments. Tissue damages as a consequence of organophosphate poisoning are frequently reported, but preventing this potentially severe complication has not been the subject of much research. We tested whether interleukin-10, a cytoprotective agent, could prevent or diminish pathological signs of tissue damages caused by organophosphate poisoning. Thirty rats were divided into three equal groups (n = 10). Group 1 (sham) did not receive any agent during the experiment. Group 2 (control) received 0.8 g/kg of fenthion intraperitoneally, followed by 6 ml/kg of intraperitoneal normal saline 30 min and 3 hr later. Group 3 (treatment) received 0.8 g/kg of fenthion intraperitoneally, followed by 2 microg/kg of interleukin-10 intraperitoneally 30 min and 3 hr later. All rats were killed under anaesthesia after 6 hr and tissue samples were obtained from liver, kidneys and lungs. Even organophosphate poisonings do not cause significant clinical problems; several degrees of damages could be observed in liver, kidneys and lungs. These damages could be reduced by interleukin-10 treatment.

Combined Low Pressure Pneumoperitoneum and Intraperitoneal Infusion of Normal Saline for Reducing Shoulder Tip Pain Following Laparoscopic Cholecystectomy

Intraabdominal CO(2) gas after laparoscopic cholecystectomy causes postoperative shoulder-tip pain. Many methods of analgesia have been used to reduce this pain, including analgesic drugs, intraperitoneal local anesthetic, intraperitoneal saline, a gas drain, heated gas, low-pressure gas, and nitrous oxide pneumoperitoneum. The aim of this study was to evaluate the efficacy of combined low-pressure CO(2) pneumoperitoneum and intraperitoneal infusion of normal saline in reducing the incidence of postoperative shoulder-tip pain. Altogether, 109 patients undergoing elective laparoscopic cholecystectomy were randomized prospectively into three groups. Patients in group A (n = 34) underwent laparoscopic cholecystectomy with 14 mmHg CO(2) pneumoperitoneum; patients in group B (n = 37) underwent laparoscopic cholecystectomy with 10 mmHg CO(2) pneumoperitoneum; and those in group C (n = 38) underwent laparoscopic cholecystectomy with 10 mmHg CO(2) pneumoperitoneum in addition to intraperitoneal normal saline infusion in the right hemidiaphragmatic area. Shoulder-tip pain was recorded on a verbal rating scale 2, 6, 12, 24, and 48 hours after operation. Twelve patients in group A (35.2 percent), six in group B (16.2 percent), and seven in group C (18.4 percent) complained of shoulder-tip pain. Hence, there was a significant decrease in the frequency of shoulder-tip pain in groups B and C in relation to group A, but there was no significant difference between groups B and C. The postoperative shoulder-tip pain scores were significantly reduced in group C at 6, 12, and 24 hours. The number of patients who required additional analgesics was also reduced in group C. Low-pressure CO(2) pneumoperitoneum reduces the number of patients complaining of shoulder-tip pain and the intensity of the pain after laparoscopic cholecystectomy. The addition of intraperitoneal normal saline infusion to low-pressure CO(2) pneumoperitoneum seems to reduce the intensity but not the frequency of shoulder-tip pain after laparoscopic cholecystectomy.

A Rat Model for Arrest of Alveolarization Induced by Antenatal Endotoxin Administration

A possible association between intrauterine inflammation and impairments of lung development has been suggested. The purpose of this study is to determine the influence of a potent proinflammatory agent, intra-amniotic lipopolysaccharide (LPS), on lung development. At 21 d gestation, an intra-amniotic injection of 1 microg LPS was administered to two subgroups of WKAH rats. One subgroup received only LPS and the other received LPS plus a fetal intraperitoneal dose of 0.25 microg granulocyte-colony stimulating factor (hrG-CSF) to produce peripheral blood neutrophilia. A third subgroup received hrG-CSF only, and a control group received maternal intraamniotic and fetal intraperitoneal normal saline. All pups were delivered by cesarean section at 22 d (term, 22.5 d) and maintained under identical conditions. Left upper lungs were obtained for morphometric analysis at 1, 3, 7, 14, 21, 45, and 60 d of age. Morphometric analysis indicated that changes in alveolar surface density (Sv), average alveolar radius (r), and numerical density of alveoli (nv) all showed that there were fewer and larger alveoli in rat lungs that had been exposed to LPS, but not to hrG-CSF alone or saline. LPS-exposed alveoli showed fewer secondary septa, suggesting an arrest of alveolarization. No destructive changes were observed in any alveoli. We concluded that these changes could be caused purely by intra-amniotic LPS. These abnormalities closely mimic those of new bronchopulmonary dysplasia. The LPS damage model may be applicable to further studies of the pathophysiology of new BPD.

Effect of interleukin-10 on pancreatic damage caused by organophosphate poisoning

Organophosphate poisoning is a common cause of severe morbidity and mortality in emergency departments. Acute pancreatitis is a frequently reported consequence of organophosphate poisoning, but preventing this potentially severe complication has not been the subject of much research. We tested whether interleukin-10, a cytoprotective agent, could prevent or diminish pathological signs of acute pancreatitis caused by organophosphate poisoning. Thirty rats were divided into three equal groups. Group 1 did not receive any agent during the experiment. Group 2 received 0.8 g/kg fenthion intraperitoneally, followed by 6 ml/kg intraperitoneal normal saline 30 min and 3 h later. Group 3 received 0.8 g/kg fenthion intraperitoneally, followed by 2 μg/kg of interleukin-10 intraperitoneally 30 min and 3 h later. All rats underwent laparotomy and thoracotomy while still under anesthesia at 6 h, and tissue samples were obtained from the pancreas. After blood samples were taken by cardiac puncture, the animals were sacrificed. Organophosphate poisoning resulted in significant elevations of serum amylase and glucose. Interleukin-10 significantly reduced pancreatic damage as determined by pathologic scoring, but not by enzyme elevations. Interleukin-10 should be considered for larger studies in other animal models to confirm its ability to decrease pancreatic damage after organophosphate poisoning treatment with interleukin-10.

The Analgesic Interaction between Ketorolac and Morphine in Radiant Thermal Stimulation Rat

Background: Previous studies have suggested synergistic analgesic drug interactions between NSAIDs and opioids in neuropathic and inflammatory pain models. The aim of this study was to investigate the analgesic drug interaction between intraperitoneal (IP) ketorolac and morphine in radiant thermal stimulation rat. Methods: Initially, we assessed the withdrawal latency time of the hindpaw to radiant thermal stimulation every 15 min for 1 hour and every 30 min for next 1 hour after IP normal saline 5 ml (control group). The latency time was changed into percent maximal possible effect (%MPE). Next, IP dose response curves were established for the %MPE of morphine (0.3, 1, 3, 10 mg/kg) and ketorolac (3, 10, 30 mg/kg) to obtain the for each agent. And we confirmed that the IP morphine effect was induced by opioid receptor through IP morphine followed by IP naloxone. At last, we injected three doses of IP ketorolac (3, 10, 30 mg/kg) mixed with one dose of morphine (2 mg/kg) for fixed dose analysis. Results: IP morphine delayed the paw withdrawal latency time dose dependently, but not ketorolac. of IP morphine was 2.1 mg/kg. And the IP morphine effect was reversed to control level by IP naloxone. IP ketorolac morphine combination showed no further additional effects on paw withdrawal latency time over morphine only group. Conclusions: IP ketorolac did not produce antinociceptive effect during radiant thermal stimulation. There was neither additional nor synergistic analgesic interaction between IP morphine and ketorolac in thermal stimulation rat.

Poly(adenosine diphosphate ribose) polymerase inhibition modulates spinal cord dysfunction after thoracoabdominal aortic ischemia-reperfusion

Spinal cord injury (SCI) remains a source of morbidity after thoracoabdominal aortic reconstruction. These studies were designed to determine whether PJ34, a novel ultrapotent inhibitor of the nuclear enzyme poly(adenosine diphosphate ribose) polymerase (PARP) could modulate neurologic injury after thoracic aortic ischemia reperfusion (TAR) in a murine model of SCI. Forty-one anesthetized male mice were subject to thoracic aortic occlusion (11 minutes) through a cervical mediastinotomy followed by 48 hours of reperfusion (TAR) under normothermic conditions. PJ34-treated mice (PJ, n = 12) were given 10 mg/kg PJ34 intraperitoneally 1 hour before ischemia and 1 hour after unclamping. The control group (UN, n = 21) received normal saline intraperitoneally 1 hour before ischemia and 1 hour after unclamping. Sham animals (n = 10) were subject to thoracic aortic exposure with no aortic clamping and similar intraperitoneal normal saline injections. PARP-1-/- (KO, n = 8) mice were subjected to the same conditions as the UN mice. Blinded observers rated murine neurologic status after TAR by using an established rodent paralysis scoring system. Murine spinal cords were subjected to cytokine (GRO-1) protein analysis as a marker of inflammation and immunohistochemical analysis (hematoxylin-eosin and PAR staining). Paralysis scores (PS) and GRO-1 levels were compared with analysis of variance, and survival data were compared with chi 2 . Immediately after TAR, UN and PJ mice had severe neurologic dysfunction (PS = 5.8 +/- 0.1 and 4.6 +/- 0.6, respectively; P > .05), which was significantly worse than the KO mice (PS = 1.0 +/- 0.7, P < .001). After 6, 24, and 48 hours KO mice had no discernable neurologic injury (PS = 0). Six hours after TAR, PJ mice significantly improved (PS = 1.1 +/- 0.73, P < .001) and remained improved at 24 (PS = 0.7 +/- 0.6) and 48 hours (PS = 0.6 +/- 0.6). UN mice did not improve their PS, and Sham mice showed no neurologic abnormality at any time during these experiments. The mortality at 48 hours was 0% for PJ and KO mice, 43% for UN (P = .012), and 0% for Sham. GRO-1 levels were significantly decreased in PJ and KO versus UN mice (UN, 583 +/- 119 vs PJ, 5.8 +/- 0 vs KO, 5.3 +/- 1.4 mg/pg; P < .0001). Immunohistochemistry showed evidence of decreased PAR staining and ventral motor neuron injury in PJ mice. Genetic deletion of PARP or inhibition of its activity (PJ34) rescued neurologic function in mice subjected to TAR. PARP inhibition might represent a novel therapeutic approach for prevention of SCI after TAR.

KETAMINE REDUCES LIDOCAINE-INDUCED SEIZURES IN MICE

Systemic toxic reactions to local anesthetics are brought about by absolute overdosage, and, most commonly, inadvertent intravascular injections. The anti-convulsant action of ketamine has been studied. However, the effect of ketamine on lidocaine-induced convulsions has not been reported. This study investigated the effect of ketamine on lidocaine-induced seizures in mice. Mice (32–41 g) were divided into 2 groups, 15 in each group, and were pretreated with intraperitoneal normal saline solution or intraperitenoeal (ip) ketamine before lidocaine. Group 1 (N = 15) received 75 mg kg ip lidocaine; Group 2 (N = 15) received 20 mg kg ketamin ip; 5 min later 75 mg kg lidokaine ip were applied. Clinical features, incidences, latencies, durations, and mortality rate of convulsions were recorded. After 75 mg kg lidocaine injection, ataxia, loss of righting reflex, and generalized tonic-clonic convulsions were seen within 2–5 min in Group 1. Generalized tonic-clonic convulsions were seen in 8 mice and deep sedation was seen in 7 mice in Group 2 (p < .05). Generalized status epilepticus occurred in one mouse in both groups. Three mice from Group l and one mouse from Group 2 died during convulsions. There were no differences between the two groups with regard to the onset and duration of seizures (p > .05). It was concluded that ketamine significantly prevented lidocaine-induced generalized tonic-clonic seizures; on the other hand, the lethality of lidocaine was least reduced by ketamine.

Characterization of T lymphocyte subtypes in endotoxin-induced uveitis and effect of pentoxifylline treatment

Purpose. The aims of the study were twofold: 1) to investigate the role of T lymphocyte subtypes in the pathogenesis of endotoxin-induced uveitis (EIU) and 2) to study the possible beneficial effect of pentoxifylline, an inhibitor of neutrophil motility, and Tumor Necrosis Factor-a on this disease. Methods. Forty-two inbred male Lewis rats were divided into seven equal groups. 200 µg of Escherichia coli 055: B55 lipopolysaccharide (LPS) was injected in one hind footpad of the Group 2, 3, 4, 5, 6, and 7 rats. Group 5, 6, and 7 rats also received concomitant intraperitoneal pentoxifylline (PTX) during food pad injection of LPS. Group 1 rats were used as controls with intra-peritoneal normal saline injection. Eight, 24, and 48 hours after treatment, the rats were euthanized. Neutrophil leukocyte, mononuclear cells, and CD4+, CD8+, and CD45RA+ cell infiltration in the anterior uveal tissue were determined either by hematoxylin-eosin or monoclonal antibody staining. Tumor Necrosis Factor-a (TNF-a) levels were also measured in the aqueous and blood samples. We compared the numbers of infiltrating cells in the different groups. Results. We found that peak infiltration of lymphocyte, neutrophils, and CD4+ cells occurred at 24 hours. However, CD8+ and CD45RA+ cell number reached their highest levels at 48 hours. There was no inflammatory cell infiltration in the control rats. Concomitant pentoxifylline treatment did not affect any of these parameters, although it effectively reduced TNF-a concentrations in the anterior chamber and the serum. Conclusion. We conclude that, 1) T lymphocytes might be involved in the pathogenesis of endotoxin-induced uveitis. 2) The potential role of pentoxifylline in the treatment of human uveitis is questionable. However, these are initial findings and need confirmation by additional studies.

Efficacy of digoxin specific Fab fragments (Digibind®) in the treatment of toad venom poisoning

Chan Su, a traditional Chinese medication, and Love Stone, a topical aphrodisiac, are both made from dried venom of the toad bufo bufo gargarizans and contain bufalin, cinobufotalin, cinobufagin, and other cardioactive steroids of the bufadienolide class. Deaths have occurred following ingestion of these products and the clinical course resembles digoxin toxicity. The purpose of this study was to determine the efficacy of digoxin specific Fab fragments in treating Chan Su poisoning. An ethanolic extract was prepared from Chan Su. Digoxin specific Fab fragments were reconstituted in normal saline to a concentration of 80 mg/ml. An approximate LD 90 dose was determined in preliminary experiments. Mice were then randomly divided into a treatment group of 15 mice and a control group of 30 mice. The treatment group was pretreated with 20 ml/kg of digoxin specific Fab fragment solution by intraperitoneal injection at t=0, followed by 10 ml/kg of digoxin specific Fab fragments intraperitoneal at t=30 min. The control group was pretreated with equal volumes of intraperitoneal normal saline at the same times. Immediately following the 30 min injection, both groups were given the estimated LD 90 dose of Chan Su extract by subcutaneous injection. An endpoint of survival at 6 h was chosen after preliminary results showed that all deaths occurred in the first 4 h. All 30 of the control mice had seizures followed by death compared to 11 seizures and 7 deaths in the 15 treatment mice. These results were statistically significant by Fisher's exact test ( p=0.00003 for mortality and p=0.009 for seizures). Digoxin specific Fab fragments are effective in the treatment of Chan Su poisoning in mice and may be effective for poisoning by other cardioactive steroids of the bufadienolide class.

Pancreatic Phospholipase A2 Induces Bacterial Translocation In Rats

The importance of pancreatic enzymes, particularly phospholipase A2 (PLA2), for bacterial translocation, which is considered to be one of the aggravating causes of acute pancreatitis, was investigated. Male rats were administered an intraperitoneal or intravenous injection of normal saline, PLA2, or amylase. Four days later, the mesenteric lymph nodes (MLNs) and portal blood of the animals were cultured. None of the animals had a positive portal blood culture. The MLNs contained enteric bacteria in 78 % of the animals given 50 mg/kg of PLA2 intraperitoneally. 5 mg/kg of PLA2 intraperitoneally, 50 mg/kg of amylase intraperitoneally, or 50 mg/kg of PLA2 intravenously showed positive cultures in 25 %, 20 %, and 11 %, respectively. None of the animals given intraperitoneal or intravenous normal saline had positive cultures of their MLNs. Intraperitoneal injection of 25mg/kg of nafamostat mesilate just before intraperitoneal PIA2 (50 mg/kg) resulted in a reduction of positive MLNs from 70 % to 30 %. The cecal myeroperoxidase (MPO) activity of animals administered 50 mg/kg of PIA2 intraperitoneally was significantly higher compared with animals administered saline intraperitoneally. These results indicate that intraperitoneal leakage of PLA2 plays an important role in bacterial translocation during acute pancreatitis and that administration of a protease inhibitor may be effective against the bacterial translocation.

The effect of intraperitoneal colchicine on the formation of peritoneal adhesions in the rat.

A double blind study was carried out to determine the effect of colchicine on the formation of intraperitoneal adhesions in the rat. Adhesions were produced by a standard method in 92 rats. The animals were than divided at random into two groups. One group (47 rats) was treated with intraperitoneal colchicine, whilst the other, the control group (45 rats) was treated with intraperitoneal normal saline in the same volume, frequency and duration. Four weeks later the animals were killed for assessment and measurement of adhesions. Two kinds of adhesions were found. 1. "Surface adhesion" - consisting of two serosal surfaces attached together; their area was significantly smaller (p less than 0.00003), and their number was lower (p less than 0.03) in the colchicine group than in the control group. 2. "Filamentous adhesions" - thin, elastic cords connecting omentum or pelvic fat bodies to other viscera; there was no significant difference in their number between the colchicine and the control group. We concluded that post-operative treatment with colchicine reduces the formation of intraperitoneal adhesions in the rat.

Effect of mast cell degranulation on gastric mucosal damage produced by sodium taurocholate in the rat

The source of the histamine released during damage to the gastric mucosa has been investigated in rats using perfused total gastric pouches. Two groups of rats were treated with either intraperitoneal normal saline or compound 48/80, an agent that produces mast cell degranulation, over a 5-day period. On the 5th day, total gastric pouches were prepared and connected to a perfusion circuit that enabled a 20-ml volume to be circulated through the pouches. The experiments consisted of three 30-min periods during which transmucosal potential difference was monitored and ionic (hydrogen and sodium) flux measured; standard acid solution was used in the first two periods and a taurocholate solution in the third. Sodium taurocholate produced a significant increase in ionic flux and fall in the potential difference, the magnitude of the changes being similar in the 48/80- and saline-treated groups. Histamine was released from the mucosa in significantly greater amounts during the taurocholate period, and the increase was similar in both groups of rats. Histological examination of the stomachs confirmed mast cell degranulation in the 48/80-treated groups. We conclude that the histamine released during mucosal damage is probably derived from the “nonmast cell pool” and that this histamine may play a role in mediating the mucosal damage.