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Crit Care (Lond). 1997;1(1):45-50. Epub 1997 Sep 26.
Beneficial effect of carboxy-PTIO on hemodynamic and blood gas changes in septic shock dogs.

Mitaka C, Hirata Y, Yokoyama K, Nagura T, Tsunoda Y, Amaha K.

Intensive Care Unit, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113, Japan.

BACKGROUND: Nitric oxide (NO) production following bacterial infection may play a physiological role in the host defense mechanism due to its antimicrobial activity. However, excess production of NO in severe infection such as sepsis has been implicated in the pathogenesis of septic shock. To determine whether a nitronyl nitroxide NO scavenger compound could prevent the hemodynamic and blood gas alterations in sepsis, bacterial lipopolysaccharide (LPS: 250ng/kg/min) was administered for 2 h in anesthetized dogs with or without infusion of carboxy-2-phenyl-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO: 0.1 mg/kg/min) for 1 h. Control animals received isotonic saline instead of LPS with or without carboxy-PTIO. RESULTS: Infusion of LPS caused a marked decrease in mean arterial pressure (MAP), metabolic acidosis, and hypoxia. These effects were reversed by co-administration of carboxy-PTIO, without affecting other hemodynamic parameters. In control animals, neither hemodynamic nor blood gas parameters changed with or without carboxy-PTIO. CONCLUSION: These results indicate that carboxy-PTIO attenuates LPS-induced hypotension, metabolic acidosis, and hypoxia by scavenging excess NO from the circulation without affecting NO synthase (NOS) activity. An NO scavenger, carboxy-PTIO, may be preferable to non-selective NOS inhibitors for the treatment of human septic shock.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11056696&dopt=Abstract [PubMed - as supplied by publisher]



Trends Microbiol. 2003 Apr;11(4):152-5.
A new turn in Rho GTPase activation by Escherichia coli cytotoxic necrotizing factors.

Aktories K, Schmidt G.

Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie, Universitat Freiburg, Otto-Krayer-Haus, Albertstrasse 25, 79104 Freiburg, Germany. klaus.aktorieharmakol.uni-freiburg.de

Various bacterial protein toxins and effectors target Rho GTPases, which are eukaryotic regulators of signal transduction pathways. Many toxins inactivate these GTPases but some, such as the cytotoxic necrotizing factors (CNFs) from Escherichia coli, activate them by deamidation. Recent studies have provided exciting new clues to the functional consequences of the activation of Rho GTPases by CNFs and its effect on the host-pathogen interaction.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12706988&dopt=Abstract



Crit Care (Lond). 1998;2(1):35-39. Epub 1998 Mar 12.
High frequency oscillatory ventilation attenuates the activation of alveolar macrophages and neutrophils in lung injury.

Shimaoka M, Fujino Y, Taenaka N, Hiroi T, Kiyono H, Yoshiya I I.

Intensive Care Unit, Osaka University Hospital, Osaka University, Yamadaoka, Suita, Osaka 565, Japan. shimaokp-icu.med.osaka-u.ac.jp

BACKGROUND: Recent investigations have shown that leukocyte activation is involved in the pathogenesis of ventilator-associated lung injury. This study was designed to investigate whether the inflammatory responses and deterioration of oxygenation in ventilator-associated lung injury are attenuated by high-frequency oscillatory ventilation (HFO). We analyzed the effects of HFO compared with conventional mechanical ventilation (CMV) on the activation of pulmonary macrophages and neutrophils in 10 female rabbits. RESULTS: After surfactant depletion, the rabbits were ventilated by CMV or HFO at the same mean airway pressure. Surfactant-depletion followed by 4 h mechanical ventilation hindered pulmonary oxygenation in both groups. Impairment of oxygenation was less severe in the HFO group than in the CMV group. In the HFO group the infiltration of granulocytes into alveolar spaces occurred more readily than in the CMV group. Compared with CMV, HFO resulted in greater attenuation of beta2-integrin expression, not only on granulocytes, but also on macrophages. CONCLUSIONS: In the surfactant-depleted lung, the activation of leukocytes was attenuated by HFO. Reduced inflammatory response correlated with decreased impairment of oxygenation. HFO may reduce lung injury via the attenuation of pulmonary inflammation.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11056708&dopt=Abstract [PubMed - as supplied by publisher]



Crit Care (Lond). 1999;3(6):167-172. Epub 1999 Nov 19.
Experience with prolonged induced hypothermia in severe head injury.

Bernard SA, MacC Jones B, Buist M.

The Intensive Care Unit, Dandenong Hospital, Dandenong, Victoria, Australia.

BACKGROUND: Recent prospective controlled trials of induced moderate hypothermia (32-34 degrees C) for relatively short periods (24-48 h) in patients with severe head injury have suggested improvement in intracranial pressure control and outcome. It is possible that increased benefit might be achieved if hypothermia was maintained for more periods longer than 48 h, but there is little in the literature on the effects of prolonged moderate hypothermia in adults with severe head injury. We used moderate induced hypothermia (30-33 degrees C) in 43 patients with severe head injury for prolonged periods (mean 8 days, range 2-19 days). RESULTS: Although nosocomial pneumonia (defined in this study as both new chest radiograph changes and culture of a respiratory pathogen from tracheal aspirate) was quite common (45%), death from sepsis was rare (5%). Other findings included hypokalaemia on induction of hypothermia and a decreasing total white cell and platelet count over 10 days. There were no major cardiac arrhythmias. There was a satisfactory neurological outcome in 20 out of 43 patients (47%). CONCLUSION: Moderate hypothermia may be induced for more prolonged periods, and is a relatively safe and feasible therapeutic option in the treatment of selected patients with severe traumatic brain injury. Thus, further prospective controlled trials using induced hypothermia for longer periods than 48 h are warranted.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11056742&dopt=Abstract [PubMed - as supplied by publisher]



Antibiot Khimioter. 2000;45(9):13-9.
[Spectrum of pneumotropic pathogens in pediatric patients with acute bronchitis and pneumonia]

[Article in Russian]

Lykova EA, Bokovoi AG, Bondarenko VM, Karazhas NV, Evseeva LF, Rybalkina TN, Dzis NB, Vorob'ev AA.

Central Clinical Hospital, Medical Centre of the Managing Department of the President of the Russian Federation, Moscow.

One hundred eighty nine children with acute bronchopulmonary infectious pathological processes were examined bacteriologically and serologically for typical pneumotropic pathogens, 47 of them being as well examined for atypical organisms. Microbial associations mainly with Mycoplasma and Pneumocystis and to a lesser extent with Chlamydia were isolated from the majority of the children. Reactivation of the cytomegalovirus infection was observed in 25 per cent of the children. Pneumonia and bronchitis due to Mycoplasma pneumoniae either as a monoagent or in associations were mainly stated in children over 7 years of age. No significant changes between the indices of the infection due to a definite organism and the active progression of the infectious process of the same etiology were revealed, though in the cases of chlamydiosis the changes reached almost 10 per cent. In cases of acute bronchitis and pneumonia the chlamydial or cytomegalovirus infection could be assumed to be of the persisting nature, mainly acute in cases of pneumococcal infection, mixed in cases of hemophilic or pneumocystic infection, primary contamination with a tendency to prolonged in cases of mycoplasmic infection. The findings of the examination and the clinical and anamnestic data showed that the clinical picture of acute pneumonia had specific features associated with the supposed etiological agents, still it could change under the action of associations of pneumotropic pathogens.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11057368&dopt=Abstract







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