harmine and Brain-Diseases

To investigate antibiotic-mediated release of tumour necrosis factor (TNF)-alpha and norharman in patients with hospital-acquired pneumonia with and without additional septic encephalopathy.. Prospective observational study with a retrospective post hoc analysis.. Surgical intensive care unit (ICU) at a university hospital.. Thirty-seven patients were consecutively included (9 patients with hospital-acquired pneumonia, 11 patients with hospital-acquired pneumonia and septic encephalopathy, 17 control patients) in the study. Pneumonia was defined according to the criteria of the American Thoracic Society.. Patients received cephalosporins for antibiotic treatment of hospital-acquired pneumonia. Blood samples were taken before, immediately after and 4 h after application of cephalosporins.. Of the pneumonia patients, 55% developed septic encephalopathy. ICU stay, complications and mortality were significantly increased. An increased release of TNF-alpha was immediately seen in all pneumonia patients after antibiotics compared to controls, whereas the level did not differ between patients with and without septic encephalopathy. Norharman was significantly increased in pneumonia patients 4 h after antibiotic treatment, in tendency more enhanced in the pneumonia patients without encephalopathy.. Patients with hospital-acquired pneumonia and septic encephalopathy had a significantly longer ICU stay with higher mortality rate compared to patients with hospital-acquired pneumonia alone. Antibiotic-mediated TNF-alpha release may induce the kynurenine pathway. TNF-alpha activates indolamine-2,3-dioxygenase with neurotoxic quinolinic acid as the end product. Norharman seems to counteract this mechanism and seems to play a role in neuroprotection. The worse outcome of patients with encephalopathy expresses the need to investigate protective factors and mechanisms.

Topics: Adult; Aged; Aged, 80 and over; Brain Diseases; Carbolines; Cephalosporins; Chi-Square Distribution; Cross Infection; Female; Harmine; Humans; Intensive Care Units; Male; Middle Aged; Pneumonia; Prospective Studies; Retrospective Studies; Sepsis; Statistics, Nonparametric; Tumor Necrosis Factor-alpha

In rats with lymphostatic encephalopathy the duration of harmine tremor was lengthened, and the brain concentrations of harmine decreased more slowly than in sham-operated controls. The tremor began simultaneously in both rat groups at coinciding brain concentrations of harmine. In rats with lymphostatic encephalopathy harmine concentrations in brain at the termination of tremor lay in the same range as in sham-operated controls. The plasma concentrations of harmine were not changed by the disease. It is concluded that during lymphostatic encephalopathy the lymphatic drug elimination from brain is impaired whereas--at least for harmine--the blood-brain barrier functions as normal.

Topics: Alkaloids; Animals; Blood-Brain Barrier; Brain; Brain Diseases; Harmine; Lymphatic System; Male; Rats; Tremor

Injection of the tremorigenic alkaloid harmine into lymphostatic encephalopathic rats leads to a longer duration of tremor and higher brain concentrations than in sham-operated controls. In lymphostatic encephalopathic as well as in normal rats different antiphlogistics shorten the tremor duration and decrease harmine concentration in brain. The antiphlogistics do not influence the plasma concentration of harmine, its protein binding and its tremorend concentration in brain. The effect of antiphlogistics in lymphostatic encephalopathic rats is considered as a consequence of the reduced blood-brain barrier permeability. Obviously in sick animals the blood-brain barrier permeability for harmine is not increased; the prolonged harmine tremor and the increased alkaloid concentration in the brain are consequences of the impaired cerebral lymphatic drainage only.

Topics: Alkaloids; Animals; Anti-Inflammatory Agents; Blood-Brain Barrier; Brain Chemistry; Brain Diseases; Harmine; Male; Rats; Time Factors; Tremor