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)

Kinetic studies were carried out in 15 very low birth weight (VLBW) infants during three courses of gentamicin (G) therapy for suspected sepsis. All received two courses but only 6 required a third course. G dosage was 2.0 +/- 0.2 mg/kg/24 h for the first and second course and 2.5 mg/kg/12 h for the third course. G dosage was adjusted to maintain serum peak G concentration of 4-8 micrograms/ml and trough concentration of 0.5-2 micrograms/ml. On the third day of therapy, a 24-hour collection of urine for creatinine (C) and G concentrations was performed in 28 of 36 cases. G clearance and G elimination rate constant were calculated based on chronological age (CA) of less than or equal to 7 (I), 8-30 (II) and greater than or equal to 31 (III) days. The mean BW and GA were 1,002 +/- 206 g and 28.4 +/- 1.5 weeks, respectively. Mean CA for the starting of therapy for each course was the first day, 19 +/- 9 and 68 +/- 26 days of life, respectively. Mean serum G peak and trough concentrations were 5.9 +/- 1.1 and 1.6 +/- 0.6 micrograms/ml for the first; 5.7 +/- 1.2 and 1.3 +/- 0.6 micrograms/ml for the second; 5.1 +/- 0.8 and 1.1 +/- 0.6 micrograms/ml for the third course of therapy. Mean apparent volume of distribution of G were 0.53 +/- 0.10 liter/kg for the first and 0.50 +/- 0.11 liter/kg for the second and third courses. Mean clearances for the three CA groups were 6.4 +/- 1.9; 7.6 +/- 3.2; 24.1 +/- 8.0 ml/min/1.73 m2 for G and 6.4 +/- 2.2; 7.7 +/- 3.1; 23.3 +/- 8.8 for C with serum C of 1.3 +/- 0.4, 1.2 +/- 0.6 and 0.6 +/- 0.4 mg%, respectively. There were no statistically significant differences for serum C, G and C clearance between CA I and II but significant differences were found for the above between CA III vs. CA I and II (p less than 0.005). G clearance closely correlated with C clearance (r = 0.99, p less than 0.001). The elimination rate constant was significantly higher after 30 days of life when CA III is compared to CA I and II or combined (p less than 0.001). This study shows that during the first month of life, VLBW sick infants still have decreased renal function and poor G clearance, therefore, G should be given every 24 h and the dose be adjusted based on individual patient serum G levels.
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PMID:Developmental pattern of gentamicin kinetics in very low birth weight (VLBW) sick infants. 651 43

The effect of sepsis on cellular calcium homeostasis in the central nervous system (CNS) was investigated using hippocampal slices of rats in which sepsis was induced by cecal ligation and puncture (CLP). Hippocampal slices were prepared from septic or sham-operated rats at 24 h after abdominal surgery. The basal intracellular calcium ([Ca2+]i) and its response to oxygen-glucose deprivation in hippocampal slices were measured for assessing cellular calcium homeostasis using fura-2 fluorescent imaging technique. The levels of [Ca2+]i were estimated by the fluorescence ratio (R340/380). Twenty-four hours after CLP, spontaneous movement was reduced and plasma lactate was increased in the septic rats in comparison with the sham-operated rats in which laparotomy was performed without CLP. Basal level of R340/380 in the CA4 ara (.72 +/- .07) was significantly higher (p < .001) in the septic group than that in the sham-operated group (.55 +/- (.06). The fluorescence ratio of septic vs. sham-operated in other hippocampal regions were .55 +/- .09 vs. .48 +/- .06 in CA1 (not significant) and .65 +/- .10 vs. .59 +/- .08 (not significant) in CA3, respectively. Increase in [Ca2+]i due to oxygen-glucose deprivation was significant in CA1 and CA3 of the septic group and in all hippocampal regions of sham-operated group. However, it was not significantly increased in CA4 of the septic group. These results suggest that regional deregulation of cellular calcium occurs in the CNS following CLP. Cellular calcium deregulation may be one of the pathogeneses occurred in clinically observed septic encephalopathy.
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PMID:Regionally different elevation of intracellular free calcium in hippocampus of septic rat brain. 890 48

We present an autopsy case of ornithine transcarbamylase (OTC) deficiency with grumose degeneration in the dentate nucleus of the cerebellum. The patient had intractable neonatal convulsions and hyperammonemia from the 3rd day after birth. Diagnosis of OTC deficiency was made based on null activity of the enzyme and four-base deletions in exon 9 of the OTC gene. Death was due to sepsis as well as disseminated intravascular coagulation at 1 year and 2 months of age. Neuropathology showed multiple cystic changes and ulegyria in the bilateral frontal and parietal lobes. Multiple cysts were associated with the region, which was infiltrated with macrophages surrounded by astroglia showing palisading pattern. Ferrugination was marked in the thalamus and severe neuronal loss with astrogliotic change in the CA1-2 area of the hippocampus. Grumose degeneration was noted in the dentate nucleus of the cerebellum. This is the first report of grumose degeneration in OTC deficiency.
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PMID:An autopsy case of ornithine transcarbamylase deficiency. 1189 Oct 99

Four bacterial isolates were recovered from the blood cultures of four patients, two of whom were from Hong Kong and two of whom were from Canada. The two Hong Kong strains were isolated from a 48-year-old man with intestinal obstruction and secondary sepsis (strain HKU16T) and from a 39-year-old man with acute appendicitis (strain HKU17), while the two Canadian strains were isolated from a 74-year-old man with biliary sepsis (strain CA1) and from a 66-year-old woman with metastatic carcinoma and sepsis (strain CA2). While the first three patients survived, the last patient died 2 weeks after the episode of bacteremia. All four isolates are strictly anaerobic, nonsporulating, gram-positive coccobacilli that were unidentified by conventional phenotypic tests and commercial identification systems. They grow on sheep blood agar as nonhemolytic pinpoint colonies after 48 h of incubation at 37 degrees C in an anaerobic environment. All are catalase positive and motile, with flagella. They produce acid from arabinose, glucose, mannose, and xylose. They do not produce indole or reduce nitrate. They are sensitive to penicillin, vancomycin, and metronidazole but resistant to cefotaxime. 16S rRNA gene sequence analysis showed 16.0%, 16.8%, and 21.0% base differences from Clostridium propionicum, Clostridium neopropionicum, and Atopobium minutum, respectively. The G+C content of strain HKU16T is 40.2% +/- 2.2%. Based on their phylogenetic affiliation, unique G+C content, and phenotypic characteristics, we propose a new genus and species, Catabacter hongkongensis gen. nov., sp. nov., to describe the bacterium, for which HKU16 is the type strain, and suggest that it be assigned to a new family, Catabacteriaceae. The gastrointestinal tract was probably the source of the bacterium for at least three of the four patients. The isolation of a catalase-positive, motile, nonsporulating, anaerobic gram-positive bacillus in clinical laboratories should raise the possibility of C. hongkongensis. Further studies should be performed to ascertain the epidemiology and other disease associations of this bacterium.
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PMID:Catabacter hongkongensis gen. nov., sp. nov., isolated from blood cultures of patients from Hong Kong and Canada. 1712 22

Encephalopathy is a common complication of sepsis. However, little is known about the morphological changes that occur in the brain during sepsis. In this study, fecal peritonitis was induced in Wistar rats, which had been monitored for 4 h before their brains were removed and samples from the CA1 area taken. In addition to higher blood pressure with a decreasing pattern and a significant drop in rectal temperature, an increased heart rate and marked respiratory failure were observed. The tissue was investigated and compared with corresponding hippocampal samples taken from sham-operated and not operated control groups. Significantly more peri-microvascular edema was found in the hippocampal CA1 area in the septic group. The percentages of the peri-microvascular edema were 158.57 +/- 3.6%, 122.84 +/- 1.5% and 120.24 +/- 1.9% in the fecal peritonitis group, sham-operated and not operated control groups, respectively. The results may suggest that the edema observed around the microvessels may participate in the pathogenesis of the septic encephalopathy probably by causing in the microvascular permeability characteristics.
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PMID:The peri-microvascular edema in hippocampal CA1 area in a rat model of sepsis. 1764 34

Perinatal hypoxia-ischemia remains the single most important cause of brain injury in the newborn, leading to death or lifelong sequelae. White matter injuries in newborn infants have long-term effects on physical, visual, motor, sensory, cognitive and social development in human infants. There is no known cure for neonatal hypoxic ischemic encephalopathy (NHIE). Activated protein C has potent anticoagulant activity due to its ability to inactivate factor Va and VIIIa. APC is the first effective biological therapy approved for the treatment of severe sepsis. Although APC is well defined as a physiological anticoagulant, emerging data suggest that it also has cytoprotective, anti-inflammatory and antiapoptotic properties. APC has been shown to provide neuroprotection in ischemic brain and spinal cord injury. Here, we propose that APC, which modulates many of these processes, may represent a promising therapeutic agent for NHIE. Seven days old Wistar Albino rat pups have been used in the study (n=42). Experimental groups in the study were: sham-operated group, APC treated group, and vehicle treated group. In hypoxia-ischemia groups, the left common carotid artery was ligated permanently on the seventh postnatal day. Two hours after the procedure, hypoxia (92% nitrogen and 8% oxygen) was applied for 2.5 h. APC were injected (intraperitoneally; i.p.) as a single dose immediately after the hypoxia period. Brain nitrite levels, neuronal cell death, and apoptosis were evaluated in both hemispheres 72 h after the hypoxic-ischemic insult. Histopathological evaluation demonstrated that APC significantly diminished the number of "apoptotic cells" in the hippocampal CA1, CA2, CA3 and gyrus dentatus regions in both hemispheres. APC treatment significantly reduced "apoptotic cell death" in both hemispheres, when compared with vehicle treated group. APC significantly preserved the number of neurons CA1, CA3 regions of the hippocampus, when compared with vehicle treated group. Our results showed that hypoxic-ischemic injury caused a significant increase in NO production. The APC-treated animals were reduced brain nitrite levels in carotid ligated hemispheres. To our knowledge, this is the first study that demonstrates a protective effect of the APC against hypoxia-ischemia in the developing brain.
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PMID:Effects of activated protein C on neonatal hypoxic ischemic brain injury. 1842 Jan 81

The development of sepsis in patient suffering from traumatic brain injury (TBI) represents a frequent complication that has been associated with worsened global and neurological outcome. In an effort to better characterize the influence of sepsis following TBI, we developed an in vivo model of combined TBI and sepsis in the rat by coupling two validated models: (1) Controlled Cortical Impact (CCI) and (2) Cecal Ligation and Puncture (CLP). Possible contributing effects of sepsis on post-traumatic outcome were evaluated as mortality rate, body weight change, neurological motor (beam balance), cognitive (Morris water maze [MWM] for memory and learning) function, histopathological damage (lesion volume, cell counts in the CA1 and CA3 hippocampal areas), and morphological indices of inflammation (activated microglia and astrocytes) for the 14-day study period. In this study, we produced a mild TBI characterized by a low mortality rate, a transient delay in weight gain, and a transient impairment in motor and cognitive functions. The histological counterpart was represented by a cortical lesion in the area of impact at 14 days post-injury, associated with cell loss in the CA1 and CA3 hippocampal regions, and scarce infiltration of microglia. The superimposition of sepsis on this mild TBI model resulted in worsening of post-injury mortality and weight loss, significant exacerbation of post-injury motor deficit and cognitive impairments, and further exacerbation of neuronal cell death in the CA3 area together with over-expression and activation of microglial cells in the peri-lesional area. Altogether, our findings indicate that sepsis, when superimposed on TBI, exerts a negative effect on the evolution of post-traumatic damage.
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PMID:Systemic sepsis exacerbates mild post-traumatic brain injury in the rat. 1925 1

Sepsis occurs in 14-37 percent of patients admitted to intensive care units and sepsis associated encephalopathy (SAE) is its severe complication. In an attempt to provide insight into the question how sepsis and SAE contributes cerebral dysfunction, apoptotic cell death was investigated in hippocampal formation, centers of adult neurogenesis and main autonomic centers which are known to regulate heart rate, respiration and other visceral activities, in cecal ligation and puncture (CLP) rat model of sepsis. Vital parameters and electrophysiological changes were monitored for the confirmation of sepsis and SAE, respectively. Apoptotic cell death was evaluated by TUNEL staining, Caspase-3 immunohistochemistry and transmission electron microscope (TEM). Significantly higher number of TUNEL positive apoptotic cells in the median preoptic nucleus, subventricular zone, dentate gyrus and CA1 and CA3 regions of the hippocampal formation were observed in CLP group and Caspase-3 immunohistochemistry and TEM findings were in line with these results, suggesting that the apoptotic cell death would bare a major role in the pathogenesis of the SAE.
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PMID:Sepsis induces apoptotic cell death in different regions of the brain in a rat model of sepsis. 2087 44

There is a growing awareness of the chronic brain injury that results from the sepsis syndrome. We review experiments in several animal models of sepsis and show in one model, cecal ligation and puncture (CLP), that permanent structural pathology matures after the initial event. Specifically, we observed after exposure to CLP significant decreased spine density on the apical tree, but not the basal tree, of dendrites in the CA1 region of the dorsal hippocampus that was accompanied by a significantly diminished arbor of the apical dendrites, by 8 weeks, but not after 2 weeks. These novel data from dendritic arborizations elaborate information about a cohort of mice that had behaved in spatial memory tasks. These results raise questions about the relationship between long-term behavioral consequences and intervention strategies.
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PMID:The brain at risk: the sepsis syndrome and lessons from preclinical experiments. 2644 May 89

Long-term sepsis survivors sustain cryptic brain injury that leads to cognitive impairment, emotional imbalance, and increased disability burden. Suitable animal models of sepsis, such as cecal ligation and puncture (CLP), have permitted the analysis of abnormal brain circuits that underlie post-septic behavioral phenotypes. For instance, we have previously shown that CLP-exposed mice exhibit impaired spatial memory together with depleted dendritic arbors and decreased spines in the apical dendrites of pyramidal neurons in the CA1 region of the hippocampus. Here we show that contextual fear conditioning, a form of associative memory for fear, is chronically disrupted in CLP mice when compared to SHAM-operated animals. We also find that the excitatory neurons in the basolateral nucleus of the amygdala (BLA) and the granule cells in the dentate gyrus (DG) display significantly fewer dendritic spines in the CLP group relative to the SHAM mice, although the dendritic arbors and gross morphology of the BLA and DG are comparable between the two groups. Moreover, the basal dendrites of CA1 pyramidal neurons are unaffected in the CLP mice. Taken together, our data indicate that the structural damage in the amygdalar-hippocampal network represents the neural substrate for impaired contextual fear memory in long-term sepsis survivors. Further, our data suggest that the brain injury caused by overwhelming sepsis alters the stability of the synaptic connections involved in associative fear. These results likely have implications for the emotional imbalance observed in human sepsis survivors.
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PMID:Preclinical models of overwhelming sepsis implicate the neural system that encodes contextual fear memory. 2787 9


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