Effect of some antimicrobials on endotoxin release in gram-negative sepsis

This study was conducted on seven groups of rats: Group 1 included a normal control group, group 2 included E. coli infected untreated rats, group 3 included infected, cefotaxime-treated [90 mg/kg] rats, group 4 included infected, gentamicin-treated [7.2 mg/kg], group 5 included infected, clindamycin-treated [27 mg/kg], group 6 included infected, cefotaxime- and clindamycin-treated rats and group 7 included infected, gentamicin- and clindamycin-treated rats. In all groups, mean arterial blood pressure, heart rate, temperature and lethality percentage were measured and blood samples were collected at 0, 3, 6, 12 and 24 hours from the antimicrobial injection. While, blood cell [WBCs] count, tumor necrosis factor-alpha [TNF-alpha], interleukin-6 [IL-6] and erythropoietin plasma levels were measured. It was concluded that antimicrobials resulting in lower amounts of free endotoxin may be more efficacious in treating Gram-negative sepsis. Also, in order to reduce the mortality during treatment of sepsis by Gram-negative E. Coli, a focus should be done on both reduction of endotoxin production and killing of bacteria. Regimen with the combination of bactericidal antimicrobial and a protein synthesis inhibitor, which offers the advantage of potent antimicrobial activity with an inhibition of endotoxin synthesis, may be an alternative to therapy by antimicrobial producing large amounts of endotoxin during its bactericidal action

Assessment of the possible capacity of the synthetic and-opioid receptor agonist DADLE in an experimental model of hypothermic ischemia and reperfusion in isolated rat heart - role of ATP-sensitive potassium channels

Efforts to prevent myocardial ischemia have focused on findings ways to block events associated with irreversible ischemic injury. The discovery of the endogenous cellular protective mechanism known as ischemic preconditioning [ipc] has risen hoping that natural pathways could be activated to help cells to overcome necrosis. Pharmacologic preconditioning has been tried to simulate ipc in cardio protection against ischemia. Aim: the aim of the present study is to assess the possible protective capacities of both [ipc] and the synthetic -opioid receptor agonist dadle in an experimental model of hypothermic ischemia and reperfusion [hir] in isolated rat heart, and to assess whether the effects of both protective measures are similarly mediated via k[atp] channels. Isolated rat hearts were divided into 7 groups: g1: is control normothermic [37°C] perfused hearts. G2 hearts were subjected to 45 min of hypothermic ischemia at 30°C, followed by 25 min of normothermic reperfusion [hir]. G3: ipc for 3 min followed by 5 min normothermic reperfusion then hir as g2. G4: dadle pretreatment [1 mg/kg] 30 min before isolated heart preparation, then the protocol of g2 was done. G5: DADLE pretreatment, then the protocol of G3. G6: glibenclamide [0.3 mg/kg] 60 min pretreatment followed by DADLE after 30 min, then the protocol of g2 was done g7: glibenclamide and dalde pretreatment, followed by protocol of g3. Both ipc and DADLE pretreatment and their combination in groups 3, 4, and 5, respectively, improved the post ischemic recovery in the form of significant increase in heart rate [hr], myocardial contractility, coronary flow [cf], and significant decrease in creative kinas [ck] in coronary effluent with a significant reduction of infarct size [is] to 6.6 +/- 1.5, 3.1 +/- 1.3, and 2.8 +/- 1.2%, respectively, when compared with g1 and g2 with is 17.2 +/- 2.2%. Glibenclamide pretreatment in g6 and g7 abolished this improvement in the post ischemic recovery when compared with groups 3, 4 and 5. The results of the present study indicate that ischemic prerconditioning [ipc] improves post ischemic recovery and reduces myocardial infract size in isolated rat heart. Pretreatment with -opioid receptor agnist DADLE mimicked the cardio protection induced by ipc, indicating an opiod receptor-mediated mechanism. Pharmacologic preconditioning by dasle and ipc has additional effects in improving the post ischemic recovery. Lastly, this cardioprotection induced by both can be abolished by the k[ATP] channel antagonist glibenclamide suggesting an involvement of the k[ATP] channel most probably mitochondrial k[ATP], as an important end-effecter of this potent cardio protective effect

Selective serotonin reuptake inhibitors and myocardial infarction

The present study was performed to test the hypothesis of a decreased risk of acute myocardial infarction [AMI] associated with selective serotonin reuptake inhibitors [SSRIs]. The rats were divided into six groups: Group 1 was the normal control group; in group 2, the rats received 1 ml distilled water orally, daily for two weeks; animals in groups 3 [fluoxetine] and 4 [paroxetine] received the drugs daily, orally in a dose of 1.8 mg/kg/day for two weeks as well as in groups 5 [fluoxetine] and 6 [paroxetine], the rats received the drugs daily, orally in a dose of 1.8 mg/kg/day for two weeks, then MI by isoprenaline [5A and 6A] was induced in the last two days and MI by coronary ligation [5B and 6B] was induced at the end of two weeks. In each group, ECG tracing was done and blood was collected for the measurements of platelet aggregation in response to adenosine diphosphate [ADP] and collagen and biomarkers for MI [total serum creatine kinase, CK-MB and cardiac troponin I]. The hearts of each group were collected for measuring the percentage of the total infarct surface area and for the histopathological examination