Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We sought to determine if a recombinant amino terminal fragment of bactericidal/permeability increasing protein (rBPI23) alters the hemodynamic responses to endotoxin. Experiments were performed on Sprague Dawley rats anesthetized with Ketamine and xylazine. In rats challenged with a 30 min infusion of 0.25 mg/kg lipopolysaccharide (LPS; Escherichia coli 0111:B4), there were early (30-90 min), significant increases in cardiac index, heart rate, and stroke volume, accompanied by significant decreases in blood pressure and total peripheral resistance. For the remainder of the 210 min observation period, cardiac index, and stroke volume progressively declined to levels significantly below those of control rats receiving only vehicles. At the same time, blood pressure and total peripheral resistance steadily increased above the vehicle control group. Infusion of 3 mg/kg of rBPI23 abolished these LPS-induced hemodynamic responses. A dose of 1.0 mg/kg of rBPI23 was associated with a modest, significant inhibition of changes evoked by LPS, whereas 0.3 mg/kg was without significant effect. Thaumatin, a control cationic protein with molecular weight and isoelectric point similar to those of rBPI23, failed to alter any responses to LPS. These results indicate that rBPI23 produces a dose-dependent inhibition of hemodynamic changes, associated with endotoxemia, and provides further support for the potential utility of rBPI23 as a therapeutic agent in the treatment of gram-negative sepsis and infection.
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PMID:Recombinant amino terminal fragment of bactericidal/permeability-increasing protein prevents hemodynamic responses to endotoxin. 826 47

Over a 10-year period, 64 children aged < or = 12 years were treated for typhoid perforation, accounting for 56% of all cases of typhoid perforation at our institution. The perforation rates in the age groups < 1, 1-4, 5-9 and 10-12 years were 4%, 1.7%, 12.4% and 29.3%, respectively, with an overall perforation rate of 10.3%. The main features were fever (93.4%) and abdominal pain and tenderness (93.4%). Thirteen children (20.3%) had associated haemorrhage, presenting as haematochezia. The incidence of perforations was 52% during the rainy season and 48% during the dry season, but the disease occurred throughout the year with a peak in October, the beginning of the dry season, which was also the time of peak occurrence of typhoid without perforation. An average of 14 h (range 5-30) was required for resuscitation. Ketamine was used for anaesthesia in most cases. Treatment was by segmental resection (67%), wedge excision (17%) and simple closure (6%). Morbidity was high (53%), and wound infection (53%) and chest infection (30%) were the most common complications. There were 25 deaths (39%), most the result of overwhelming sepsis. Late presentation at > 7 days was associated with high mortality (p < 0.05). Typhoid perforation continues to be a scourge in children in developing countries and, in addition to preventive measures such as improved sanitation and the provision of safe water supplies, public enlightenment is necessary to ensure early presentation and improved survival.
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PMID:Typhoid ileal perforation in children: a scourge in developing countries. 1071 13

The aim of this study was to elucidate the effects of midazolam and ketamine on neuromuscular blockade induced by non-depolarizing muscle relaxants (NDMRs) under the condition of sepsis induced by panperitonitis. A CLP operation (laparotomy, cecal ligation, and puncture of the cecum; septic group) or sham laparotomy (sham group) was performed on rats under O2-isoflurane anesthesia. At 18 hours after the operation, isometric twitch tensions of rat nerve-hemidiaphragm preparations elicited by indirect or direct stimulation at 0.1 Hz were measured. Midazolam enhanced the dTc (1 microM)-induced twitch depression (p < 0.05) at a high concentration (10 microM) in the septic group but not in the sham group. Ketamine enhanced the dTc (1 microM)-induced twitch depression in the sham group (p < 0.01) but not in the septic group. Midazolam and ketamine had no effect on directly elicited twitch tensions in either group. The results indicate that sepsis facilitates the midazolam-induced enhancement of the neuromuscular blocking effect of dTc but, conversely, inhibits the ketamine-induced enhancement. Sepsis elicits manifold alterations in the influence of intravenous anesthetics and sedatives on NDMR-induced neuromuscular blockade.
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PMID:The effects of midazolam and ketamine on D-tubocurarine-induced twitch depression in septic rat diaphragm. 1195 90

Ketamine may be advantageous for anesthesia of patients with sepsis caused by gram-negative bacteria, because ketamine may suppress LPS-induced production of proinflammatory cytokines, such as TNFalpha and IL-6. NFkappaB is an important transcription factor that is involved in the post-transcriptional regulation of mRNA expression for several immunoinflammatory mediators in response to endotoxemia. This study examined the effect of ketamine on NFkappaB activation and TNFalpha production in rat peripheral blood mononuclear cells (PBMC). The PBMC were incubated in the presence or absence of LPS and with graded concentrations of ketamine. The culture supernatants and cells were collected for each group and duration of incubation. Activation of NFkappaB was determined by electrophoretic mobility shift assay (EMSA), and the expression of IkappaBalpha, its inhibitor, in PBMC was analysed by Western blotting. TNFalpha levels in the supernatants were measured using a specific enzyme-linked immunosorbent assay (ELISA). LPS stimulation of rat PBMC increased TNFalpha production and NFkappaB activation, with corresponding loss of IkappaBalpha. Ketamine significantly reduced the LPS-induced NFkappaB activation and inhibited TNFalpha production in a dose-dependent manner. These in vitro findings suggest that ketamine is a potent inhibitor of NFkappaB activation and cytokine production in rat PBMC.
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PMID:Ketamine reduces NFkappaB activation and TNFalpha production in rat mononuclear cells induced by lipopolysaccharide in vitro. 1217 93

The effects of ketamine on endotoxin-induced NF-kappaB activation and TNF-alpha expression were studied in vivo. A sepsis model was created by bolus injection of endotoxin (5 mg/kg) into the tail vein of adult Wistar rats. The rats were immediately treated with various doses of ketamine (0.5, 5, or 50 mg/kg) or 0.9% NaCl (10 ml/kg) i.p. At 1, 4, or 6 hr post-treatment, NF-kappaB and TNF-alpha were assayed in the intestine, liver, and lung by electrophoretic mobility shift assay (EMSA) and reverse-transcription polymerase chain reaction (RT-PCR), respectively. Serum TNF-alpha was analyzed by ELISA. Endotoxin enhanced NF-kappaB activity and TNF-alpha expression in the intestine, liver, and lung and it increased TNF-alpha concentration in serum. Ketamine dosages 0.5 mg/kg suppressed the endotoxin-induced NF-kappaB activation and TNF-alpha expression in the intestine. The lowest dose to inhibit NF-kappaB activity and TNF-alpha expression in the lung was 5 mg/kg. Ketamine did not inhibit endotoxin-induced NF-kappaB activity or TNF-alpha expression in the liver; ketamine itself at a dose of 50 mg/kg enhanced NF-kappaB activity and TNF-alpha expression in the liver. Ketamine dosage 0.5 mg/kg inhibited endotoxin-induced TNF-alpha elevation in the serum. In conclusion, ketamine can suppress the induction of NF-kappaB and TNF-alpha by endotoxin in vivo. Subanesthetic dosages of ketamine have an anti-inflammatory effect, but large dosages may be harmful.
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PMID:Effect of ketamine on NF-kappa B activity and TNF-alpha production in endotoxin-treated rats. 1522 31

Ketamine is the only intravenous anesthetic that causes an increase in mean arterial pressure without compromising cardiac output. These beneficial effects are basically linked to stimulation of the sympathetic nervous system, inhibition of adenosine triphosphate-sensitive potassium channels and interactions with the nitric oxide pathway. Experimental and clinical studies have shown that ketamine exerts antiinflammatory properties by inhibiting the release of proinflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6. In addition, there is increasing evidence that early ketamine administration reduces mortality in experimental sepsis models. In view of the current literature ketamine appears to represent a beneficial therapeutic option for long-term sedation of patients with arterial hypotension resulting from sepsis and systemic inflammatory response syndrome (SIRS). However, it has to be taken into account that ketamine inhibits endothelial nitric oxide synthase, thereby potentially aggravating impaired (micro) regional blood flow in sepsis. Future studies are required to investigate the role of ketamine in the treatment of patients with sepsis and SIRS.
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PMID:[Role of ketamine in sepsis and systemic inflammatory response syndrome]. 1677 27

Ketamine was reported to decrease cytokine production and improve survival after Escherichia coli-induced sepsis. We examined whether ketamine decreased interleukin (IL)-6 production and improved survival after 1) burn injury or 2) burn injury combined with sepsis (E. coli) at 24 h. Ketamine (10 mg/kg) or saline was given at 1 h after burn injury (G 1, 2, 5, 6), 24 h after burn injury (G 3, 4), or at E. coli inoculation (G 7, 8). Mortality was recorded for 7 days and IL-6 was measured in serum at 6 h after burn (G 1-2), 30 h after burn (G 3-4), or 6 h after sepsis (30 h after burn) (G 5-8). Burn injury only: Ketamine given immediately (1 h) after burn injury but not 24 h after, decreased the burn-induced increase of IL-6 but did not improve survival. Burn injury + sepsis: Ketamine given immediately after burn injury did not significantly decrease the sepsis-induced increase of IL-6 or improve survival. In contrast, ketamine given immediately after sepsis significantly improved survival (46.1% versus 13.3%, P = 0.008) and decreased IL-6 production (72,640 +/- 40,990 vs 332,300 +/- 32,300 pg/mL, P = 0.008). We conclude that ketamine therapy improves survival in burn injury followed by sepsis. This beneficial effect is probably achieved through interference with the inflammatory cascade, as evidenced by attenuation of the proinflammatory marker IL-6.
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PMID:Ketamine improves survival in burn injury followed by sepsis in rats. 1686 23

Sepsis and shock are severe conditions that, when together, may cause multiple organ failure. The anesthesiologist must be able to take a careful history and physical, as well as be aware that additional tests are necessary to assess the patient status, as preoperative systemic blood pressure is not indicative of adequate volume status. In preparation for surgery, one must anticipate dysfunction and have adequate blood products and antibiotic at hand. Ketamine is notable for induction in these patients because it is less likely to decrease systemic vascular resistance too quickly. One must not take this lightly, as death may ensue if proper management is not taken.
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PMID:Septic shock: review and anesthetic considerations. 1751 Nov 84

This study was designed to investigate the effects of ketamine on levels of inflammatory cytokines, nuclear factor-kappa B (NF-kappaB) and Toll-like receptors (TLRs) in rat intestine during polymicrobial sepsis, induced by cecal ligation and puncture (CLP). After the induction of sepsis or sham-operation, the rats were treated with ketamine (2.5, 5 or 10 mg/kg) or saline (10 ml/kg). At 2, 4 or 6 h post-operation, the intestinal concentrations of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6, were determined by enzyme-linked immunosorbent assay (ELISA). Activity of NF-kappaB in rat intestine was assessed by electrophoretic mobility shift assay (EMSA). And expressions of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) of rat intestine were examined by reverse transcription-polymerase chain reaction (RT-PCR). We found that TNF-alpha and IL-6 concentrations, NF-kappaB activity, TLR2 and TLR4 expressions in rat intestine were increased after CLP. At the doses of 5 and 10 mg/kg, ketamine suppressed CLP-induced elevation of IL-6. Ketamine 2.5, 5 and 10 mg/kg after CLP decreased intestinal TNF-alpha level and NF-kappaB activity, and inhibited TLR2 and TLR4 expressions as well. These results suggest that ketamine may have anti-inflammatory effects, such as suppressing the levels of inflammatory cytokines and attenuating NF-kappaB activity, during polymicrobial sepsis. And these anti-inflammatory effects possibly correlate with the inhibitory influence of ketamine on TLR2 and TLR4 expressions.
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PMID:Effects of ketamine on levels of cytokines, NF-kappaB and TLRs in rat intestine during CLP-induced sepsis. 1757 Mar 24

There are two optical isomers of the 2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone ketamine: S(+) ketamine and R(-) ketamine. Effects of this drug are mediated by N-methyl-d-aspartate (NMDA), opioid, muscarinic and different voltage-gated receptors. Clinically, the anaesthetic potency of the S(+)-isomer is approximately three to four times that of the R(-)-isomer, which is attributable to the higher affinity of the S(+)-isomer to the phencyclidine binding sites on the NMDA receptors. Ketamine is water- and lipid-soluble, allowing it to be administered conveniently via various routes and providing extensive distribution in the body. Ketamine metabolism is mediated by hepatic microsomal enzymes. It causes bronchodilation and stimulation of the sympathetic nervous system and cardiovascular system. In clinics, ketamine and particularly S(+)-ketamine are used for premedication, sedation, and induction and maintenance of general anaesthesia, which is than termed "dissociative anaesthesia". Ketamine and its S(+)-isomer are ideal anaesthetic agents for trauma victims, patients with hypovolemic and septic shock and patients with pulmonary diseases. Even subanaesthetic doses of this drug have analgesic effects, so ketamine is also recommended for post-operative analgesia and sedation. The combination of ketamine with midazolam or propofol can be extremely useful and safe for sedation and pain relief in intensive care patients, especially during sepsis and cardiovascular instability. In the treatment of chronic pain ketamine is effective as a potent analgesic or substitute together with other potent analgesics, whereby it can be added by different methods. There are some important patient side-effects, however, that limit its use, whereby psycho-mimetic side-effects are most common.
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PMID:Ketamine. 1817 98


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