tetracycline and Multiple-Organ-Failure

Despite recovery of hemodynamics by fluid resuscitation after hemorrhage, development of the systemic inflammatory response and multiple organ dysfunction syndromes can nonetheless lead to death. Minocycline and doxycycline are tetracycline derivatives that are protective in models of hypoxic, ischemic, and oxidative stress. Our aim was to determine whether minocycline and doxycycline protect liver and kidney and improve survival in a mouse model of hemorrhagic shock and resuscitation.. Mice were hemorrhaged to 30 mmHg for 3 h and then resuscitated with shed blood followed by half the shed volume of lactated Ringer's solution containing tetracycline (10 mg/kg), minocycline (10 mg/kg), doxycycline (5 mg/kg), or vehicle. For pretreatment plus posttreatment, drugs were administered intraperitoneally prior to hemorrhage followed by second equal dose in Ringer's solution after blood resuscitation. Blood and tissue were harvested after 6 h.. Serum alanine aminotransferase (ALT) increased to 1,988 and 1,878 U/L after posttreatment with vehicle and tetracycline, respectively, whereas minocycline and doxycycline posttreatment decreased ALT to 857 and 863 U/L. Pretreatment plus posttreatment with minocycline and doxycycline also decreased ALT to 849 and 834 U/L. After vehicle, blood creatinine increased to 134 µM, which minocycline and doxycycline posttreatment decreased to 59 and 56 µM. Minocycline and doxycycline pretreatment plus posttreatment decreased creatinine similarly. Minocycline and doxycycline also decreased necrosis and apoptosis in liver and apoptosis in both liver and kidney, the latter assessed by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) and caspase 3 activation. Lastly after 4.5 h of hemorrhage followed by resuscitation, minocycline and doxycycline (but not tetracycline) posttreatment improved 1-week survival from 38% (vehicle) to 69% and 67%, respectively.. Minocycline and doxycycline were similarly protective when given before as after blood resuscitation and might therefore have clinical efficacy to mitigate liver and kidney injury after resuscitated hemorrhage.

Topics: Alanine Transaminase; Animals; Apoptosis; Biomarkers; Caspase 3; Creatinine; Cytoprotection; Disease Models, Animal; Doxycycline; Fluid Therapy; Hemodynamics; Kidney; Liver; Male; Mice, Inbred C57BL; Minocycline; Multiple Organ Failure; Necrosis; Protective Agents; Resuscitation; Shock, Hemorrhagic; Tetracycline; Time Factors

The authors report on a female patient of 26 years of age suffering from malaria tropica infection in her 36th week of pregnancy with fatal outcome. The newborn (after performance of Caesarean section) was infected connatally. Although infections with malaria are rare in Europe today--especially during pregnancy--there is a probability of rising incidence on account of increasing international tourism. Therapeutic problems are expected to multiply due to the resistance of Plasmodia to antiparasitary medication. Additionally pregnancy involves the risk of a more severe course of the disease in the mother. Pregnant women should be discouraged from travelling to countries with malarial risk because of the likelihood of a high rate of abortion, danger of intrauterine retardation, increased incidence of premature deliveries and risk of connatal infection of the newborn. If such warnings cannot be heeded, the persons concerned must be given all relevant information on conventional preventive measures in accordance with WHO recommendations and drug prophylaxis as recommended by a hospital or institution dealing with tropical diseases according to updated standards. The measures to be taken must be adapted to the individual risk of exposure of the patient.

Topics: Adult; Cesarean Section; Diagnosis, Differential; Female; Humans; Infant, Newborn; Malaria, Falciparum; Multiple Organ Failure; Oxygen; Pregnancy; Pregnancy Complications, Parasitic; Pregnancy Trimester, Third; Quinine; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Tetracycline

Two patients were admitted directly to our Intensive Care Unit in acute respiratory failure due to pneumonia with septicaemic shock, renal and hepatic impairment. Sputum and blood cultures failed to grow any organisms and despite broad spectrum antibiotic therapy for 7 days, neither patient improved. Diagnosis of the rare pneumonic form of psittacosis was made following a raised titre. After treatment with tetracyclines, both patients made a rapid recovery. Retrospective direct questioning revealed that they had close contact with psitacine birds.

Topics: Diagnosis, Differential; Humans; Male; Middle Aged; Multiple Organ Failure; Pneumonia; Psittacosis; Serologic Tests; Tetracycline