[Carbamate and organophosphate poisoning]. / Intossicazione da carbamati e da organo-fosfati.

Carbamate and organophosphate poisoning is a well known toxicological problem in developing countries, but still has, even in industrialized ones, a high mortality rate and a frequent invalidating outcome. Serious problems especially arise from cardiac (toxic myocarditis, QT prolongation, and other ventricular arrhythmias), muscular (intermediate syndrome, OPIDN), and neuro-behavioral (regressive psychosis, cognitive, mnesic and perceptive alterations) sequelae. Such complications, caused by direct neuronal, cardiac, and muscular damage, sneaky appear immediately after resolution of cholinergic crisis. Early establishment of antidotal (atropine + oximes) and supportive therapy, while reducing duration and seriousness of cholinergic crisis, should increase survival rates. In order to improve "quoad valetudinem" prognosis, widespread use of benzodiazepines is still recommended: such drugs antagonize some central signs and symptoms of cholinergic attack insensitive to atropine (fasciculations, muscular spasms, seizures, anxiety, psychomotor agitation). Moreover, they attenuate neuronal, cardiac, and muscular damage, caused by cholinergic overstimulation, which is responsible for invalidating outcome.

[Ketorolac for prevention of acute postoperative pain]. / Profilassi con ketorolac del dolore acuto postoperatorio.

BACKGROUND: Since NSAIDs are competitive antagonists of cyclooxygenase, they prevent the biosynthesis of prostaglandins, responsible for enhanced nociceptive sensitization and primary hyperalgesia. If NSAIDs administration is performed after eicosanoids cascade activation by surgical trauma, already released prostaglandins can exert their hyperalgesic effects for a finite time. Therefore prophylactic administration of NSAIDs (pre-emptive analgesia) should improve their effectiveness on acute postoperative pain. AIM OF STUDY: To assess the analgesic effect of preoperatively administered ketorolac, compared with its administration after surgical trauma. MATERIALS AND METHODS: Thirty adult patients, ASA physical status I-II, undergoing elective septoplasty, were allocated randomly in two groups, depending on timing of i.v. administration of ketorolac 0.4 mg/kg: 10 min before induction (group I); or 5 min after décollement of nasal septum cartilaginoid plan (group II). No other analgesic drugs were given. Postoperative pain was assessed with objective (SAP, DAP, HR) and subjective (VAS, BS 11) methods at 60, 90, 120, 150, and 180 min after the end of surgery. Rate and severity of any side-effect were recorded. RESULTS: Both VAS and BS 11 showed significant better pain relief after preoperative ketorolac at all time, without any adverse effect. Same result was shown by SAP at 60 and 90 min postoperatively. CONCLUSIONS: Due to prevention of nociceptive sensitization of prostaglandins released by tissue trauma, prophylactic NSAIDs administration to surgical patients with mild to moderate postoperative pain can improve their antinociceptive effects.

Cytotoxic activity of an anti-transferrin receptor immunotoxin on normal and leukemic human hematopoietic progenitors.

The process of cellular iron uptake involves a specific receptor for the plasma carrier transferrin and a pathway of receptor-mediated endocytosis. Transferrin receptor expression is closely related to the rate of cell proliferation, and conjugates between anti-transferrin receptor monoclonal antibodies and toxins have been shown to have potent cytotoxic activity. We have constructed an anti-transferrin receptor immunotoxin by conjugating the anti-transferrin receptor monoclonal antibody B3/25 to a ribosome-inactivating protein, the saporin-6 (SO6), which is derived from the seeds of the plant Saponaria officinalis. The immunotoxin B3/25-SO6 was tested for in vitro cytotoxic activity against the human cell lines K-562 and HL-60 and against normal human bone marrow hematopoietic progenitors and acute myeloid leukemia clonogenic cells. The immunotoxin proved to be an effective inhibitor of K-562 and HL-60 clonogenic cell growth, in vitro colony formation being completely inhibited at immunotoxin concentrations ranging from 10(-7) to 10(-10) M. B3/25-SO6 markedly reduced the recloning efficiency of HL-60 clonogenic cells at 10(-12) M. Exposure of HL-60 cells in suspension culture to 10(-9) M B3/25-SO6 for 48-72 h completely abolished their clonogenic potential. The immunotoxin was also found to be cytotoxic against normal human bone marrow progenitor cells (burst-forming unit-erythroid and colony-forming unit-granulocyte, macrophage) in a dose-dependent manner. However, exposure of normal colony-forming unit-granulocyte, macrophage in suspension culture to 10(-9) M B3/25-SO6 for 72 h resulted in only 50% suppression of their clonogenic potential. Finally, B3/25-SO6 was found to be a potent inhibitor of in vitro growth of acute myeloid leukemia clonogenic cells. The cytotoxic effects of B3/25-SO6 were shown to be specific, since both saporin alone and irrelevant immunotoxins did not have any effect in the cellular systems examined. We conclude that the immunotoxin B3/25-SO6 has dose-related cytotoxic effects on both normal and leukemic human hematopoietic progenitors. Since there are substantial differences between normal and leukemic progenitors with respect to the proportion of cycling cells and the expression of transferrin receptors, B3/25-SO6 or similar immunotoxins may have clinical application in bone marrow-purging procedures.