[Suicide attempts with castor beans and jequirity beans]. / Tentamen suicidii met wonderbonen en paternosterbonen.

BACKGROUND: Intoxications by beans can have serious consequences. We describe 2 auto-intoxications using castor beans and jequirity beans with the toxins ricin and abrin, respectively. Both toxins have similar mechanisms of action. When taken orally, a toxic mucositis develops causing dehydration, gastrointestinal blood loss and multi-organ failure. Knowledge about pathophysiology is important for risk assessment and treatment. CASE DESCRIPTION: Patient A presented 27 hours after ingestion of the castor beans with frequent vomiting and watery diarrhea. Patient B presented 45 minutes after ingestion of jequirity beans without physical complaints. Gastric lavage and bowel lavage was started. The clinical course in both patients was mild. The severity of toxicity depends on how much the beans have been chewed and the amount of ricin/abrin per bean. CONCLUSION: Intoxications with ricin or abrin can be potentially serious. There is no antidote. Treatment consists of anti-absorptive measures and best supportive care.

Toxicological analysis of azide and cyanide for azide intoxications using gas chromatography.

Azide is a highly toxic chemical agent to human being. Accidental, but also intentional exposure to azide occurs. To be able to confirm azide ingestion, we developed a method to identify and quantify azide in biological matrices. Cyanide was included in the method to evaluate suggested in vivo production of cyanide after azide ingestion. Azide in biological matrices was first derivatized by propionic anhydride to form propionyl azide. Simultaneously, cyanide was converted into hydrogen cyanide. After thermal rearrangement of propionyl azide, ethyl isocyanate was formed, separated together with hydrogen cyanide by gas chromatography (GC) and detected using a nitrogen phosphorous detector (NPD). The method was linear from 1.0-100 µg/mL for both analytes, and azide was stable in human plasma at -20°C for at least 49 days. Azide was measured in the gastric content of two cases of suspected azide ingestion (case 1:1.2 mg/mL, case 2:1.5 mg/mL). Cyanide was only identified in the gastric content of case 1 (approximately 1.4 µg/mL). Furthermore, azide was quantified in plasma (19 µg/mL), serum (24 µg/mL), cell pellet (21 µg/mL) and urine (3.0 µg/mL) of case 2. This method can be used to confirm azide and cyanide exposure, and azide concentrations can be quantified in several biological matrices.

Dermaseptins, Multifunctional Antimicrobial Peptides: A Review of Their Pharmacology, Effectivity, Mechanism of Action, and Possible Future Directions.

Dermaseptins are a group of α-helical shaped polycationic peptides isolated from the Hylid frogs, with antimicrobial effects against bacteria, parasites, protozoa, viruses in vitro. Besides, anti-tumor effects have been demonstrated. However, few animal experiments and no clinical trials have been conducted thus far. This review summarizes the current knowledge on the pharmacology, ethno pharmacology, effectivity against infectious pathogens and tumors cells and the mechanism of action of the Dermaseptins. Future research should focus on further clarification of the mechanisms of action, the effectivity of Dermaseptins against several cancer cell lines and their applicability in humans.

Cell-type-specific downregulation of heme oxygenase-1 by lipopolysaccharide via Bach1 in primary human mononuclear cells.

Heme oxygenase (HO)-1 is the inducible isoform of the heme-degrading enzyme HO, which is upregulated by multiple stress stimuli. HO-1 has major immunomodulatory and anti-inflammatory effects via its cell-type-specific functions in mononuclear cells. Contradictory findings have been reported on HO-1 regulation by the Toll-like receptor (TLR) 4 ligand lipopolysaccharide (LPS) in these cells. Therefore, we reinvestigated the effects of LPS on HO-1 gene expression in human and murine mononuclear cells in vitro and in vivo. Remarkably, LPS downregulated HO-1 in primary human peripheral blood mononuclear cells (PBMCs), CD14(+) monocytes, macrophages, dendritic cells, and granulocytes, but upregulated this enzyme in primary murine macrophages and human monocytic leukemia cell lines. Furthermore, experiments with human CD14(+) monocytes revealed that activation of other TLRs including TLR1, -2, -5, -6, -8, and -9 decreased HO-1 mRNA expression. LPS-dependent downregulation of HO-1 was specific, because expression of cyclooxygenase-2, NADP(H)-quinone oxidoreductase-1, and peroxiredoxin-1 was increased under the same experimental conditions. Notably, LPS upregulated expression of Bach1, a critical transcriptional repressor of HO-1. Moreover, knockdown of this nuclear factor enhanced basal and LPS-dependent HO-1 expression in mononuclear cells. Finally, downregulation of HO-1 in response to LPS was confirmed in PBMCs from human individuals subjected to experimental endotoxemia. In conclusion, LPS downregulates HO-1 expression in primary human mononuclear cells via a Bach1-mediated pathway. As LPS-dependent HO-1 regulation is cell-type- and species-specific, experimental findings in cell lines and animal models need careful interpretation.

Rosuvastatin increases extracellular adenosine formation in humans in vivo: a new perspective on cardiovascular protection.

OBJECTIVE: Statins may increase extracellular adenosine formation from adenosine monophosphate by enhancing ecto-5'-nucleotidase activity. This theory was tested in humans using dipyridamole-induced vasodilation as a read-out for local adenosine formation. Dipyridamole inhibits the transport of extracellular adenosine into the cytosol resulting in increased extracellular adenosine and subsequent vasodilation. In addition, we studied the effect of statin therapy in a forearm model of ischemia-reperfusion injury. METHODS AND RESULTS: Volunteers randomly received rosuvastatin or placebo in a double-blind parallel design (n=21). The forearm vasodilator response to intraarterial dipyridamole was determined in the absence and presence of the adenosine antagonist caffeine. During a separate visit the vasodilator response to nitroprusside and adenosine was established. In addition, healthy men were randomly divided in 3 groups to receive either placebo (n=10), rosuvastatin (n=22), or rosuvastatin combined with intravenous caffeine (n=12). Subsequently, volunteers performed forearm ischemic exercise. At reperfusion, Tc-99m-labeled annexin A5 was infused intravenously and scintigraphic images were acquired, providing an early marker of cell injury. Rosuvastatin treatment significantly increased the vasodilator response to dipyridamole, which was prevented by caffeine. Rosuvastatin did not influence the response to either sodium nitroprusside or adenosine indicating a specific interaction between rosuvastatin and dipyridamole, which does not result from an effect of rosuvastatin on adenosine clearance nor adenosine-receptor affinity or efficacy. Rosuvastatin increased tolerance to ischemia-reperfusion injury, which was attenuated by caffeine. CONCLUSIONS: Rosuvastatin increases extracellular adenosine formation, which provides protection against ischemia-reperfusion injury in humans in vivo. Therefore, statins and dipyridamole may interact synergistically.