Hidden chaos factors inducing random walks which reduce hospital operative efficiency.

Operative parameters of La Fuenfría Hospital such as: hospitalized patients; daily admissions and discharges were studies for the hospital as a whole, and for each hospital's service unit (henceforth called 'services'). Conventional statistical analyzes and fractal dimension analyzes were performed on daily In-Patient series. The sequence of daily admissions and patients staying on each service were found to be a kind of random series known as random walks (Rw), sequences where what happens next, depends on what happens now plus a random variable. Rw analyzed with parametric or nonparametric statistics may simulate cycles and drifts which resemble seasonal variations or fake trends which reduce the Hospital's efficiency. Globally, inpatients Rw s in LFH, were found to be determined by the time elapsed between daily discharges and admissions. The factors determining LFH R were found to be the difference between daily admissions and discharges. The discharges are replaced by admissions with some random delay and the random difference determines LFH Rw s. These findings show that if the daily difference between admissions and discharges is minimized, the number of inpatients would fluctuate less and the number of unoccupied beds would be reduced, thus optimizing the Hospital service.

Tityus discrepans scorpion venom activates platelets through GPVI and a novel Src-dependent signaling pathway.

In humans and other mammals, Tityus discrepans (Td) scorpion envenomation produces a variety of systemic effects including respiratory distress, a generalized inflammatory reaction, modulation of blood pressure, fibrin formation, and platelet activation. For many of these effects, the venom components and underlying mechanisms are not known. In the present study, we demonstrate that Td venom (TdV) stimulates integrin αIIbß3-dependent aggregation of washed human and mouse platelets downstream of Src kinase activation. The pattern of increase in tyrosine phosphorylation induced by TdV in human platelets is similar to that induced by the collagen receptor GPVI, and includes FcR γ-chain, Syk, and PLC γ 2. Confirmation of GPVI activation by TdV was achieved by expression of human GPVI in chicken DT40 B cells and use of a reporter assay. To our surprise, TdV was able to activate mouse platelets deficient in the GPVI-FcR γ-chain complex through a pathway that was also dependent on Src kinases. TdV therefore activates platelets through GPVI and a second, as yet unidentified Src kinase-dependent pathway.

Ischemic Stroke in a Child after a Probable Scorpion Sting.

Scorpion stings are common emergencies in the tropics. Species-specific antivenom therapies are available. However, fatalities resulting from scorpion stings remain a public health concern in many settings. Children residing in rural towns and peri-urban areas represent the most vulnerable populations. Delays in the diagnosis of scorpion stings often occur as a result of the non-specific clinical presentations, which then lead to life-threatening complications. We report a 2-year-old Venezuelan boy presenting with acute pancreatitis and pulmonary edema without an identifiable cause 48 hours after his initial symptoms. We administered antivenom therapy when an undetected scorpion sting was suspected. Despite some initial clinical improvement with respect to his acute pancreatitis, pulmonary edema, and coagulation abnormalities, our patient experienced an ischemic stroke. Fortunately, our patient did demonstrate some neurological improvement. Although acute pancreatitis and pulmonary edema are known end-organ damage manifestations of the sting of Tityus in the Americas, our particular case illustrates the risk of ischemic stroke.

Scorpion venom complexity fractal analysis. Its relevance for comparing venoms.

We analyzed the venom elution pattern of 15 scorpions species. Data were scanned at 1 Hz and stored digitally. Approximate fractal dimension (D) [Sevcik (1998)] was calculated for minutes 0-60 of the elutions. D was calculated for either the whole time range, or calculated using a window of 500 points, which was displaced by one time increment recursively, and stored [(t(i),D(i)) sets]. We avoid the term complexity as much as possible since defining complexity is difficult; instead we propose the term contortedness and represent it by the variable Q=D-1. To compare venom contortednesses of different species, a phase plot with their (t(i),Q(i)) sets was constructed and determination coefficient (d(s)) were calculated squaring the Spearman rank correlation coefficient. (t(i),Q(i)) sets of several elutions of the same species were averaged and compared with other species finding that some were amazingly similar (Tityus clathratus vs Tityus caripitensis, d(s) = 0.813). Tityus discrepans was similar to 6 of 8 species of the same genus (d(s) ranging from 0.23 to 0.49), and also similar to Centruroides gracilis and Chactas laevipes (d(s) 0.54 and 0.49, respectively). Serendipitously,T. discrepans was chosen many years ago to produce anti-Tityus antivenom in Venezuela; perhaps the clinical success in neutralizing the venom of the other known Venezuelan Tityus, stems from the mimetism of this venom with the remaining species' venom.

On the presence of antibodies against bovine, equine and poultry immunoglobulins in human IgG preparations, and its implications on antivenom production.

Specific immunoassays were developed to detect anti-horse, anti-chicken and anti-bovine immunoglobulins in human IgG preparations. Three samples of 5% human IgG for intravenous use ("Inmunoglobulina G Endovenosa al 5%"(trade mark), Quimbiotec CA), were studied. All samples were produced from pools of >2500 plasma units from different donors. One sample was produced from an only Venezuelan plasma pool (2660 donors) and the other two were produced from a 1:1 blend of Venezuelan and Canadian plasma pools. The amounts of human IgG detected were 0.017 (0.015,0.020) mg/ml (n=18) against horse IgG, 0.37 (0.28, 0.48) mg/ml (n=18) against cattle IgG and 1.27 (1.15, 1.40) mg/ml (n=15) against chicken IgY. Similar results were obtained on individual Venezuelan plasma samples. The differences probably reflect the consumption and antigenicity of meat. Poultry and bovine meat are widely consumed in Venezuela and Canada, while equine meat is not consumed; also chicken is more heterologous to man and may be more antigenic than bovine meat. This suggests that when IgY immunotherapeutics are used in populations with an important dietary component of poultry meat and eggs, there is a risk of producing untoward reactions and less efficient antivenoms.

[Effect of Tityus discrepans scorpion venom on global coagulation test. Preliminary studies]. / Efecto del veneno del escorpión Tityus discrepans sobre las pruebas globales de la coagulación. Estudios preliminares.

Tityus discrepans (Td) scorpion venom modifies clotting times in humans. We studied the in vitro venom effect on partial thromboplastin time (PTT), prothrombin time (PT) and its direct clotting activity, using fresh human plasma and purified fibrinogen as substrates. Whole venom (WV) was fractioned with a Protein Pak 125 molecular exclusion column (0.5 mL/min, CH3COONH4 20 mM, pH 4.7). Six fractions (F1 through F6) with retention times ranging from 12.8 to 31 min were obtained. WV (78 to 625 microg/mL) and fraction F1 (10 to 42.5 microg/mL), shortened PTT; WV (700 to 1000 microg/mL) and fraction F6 (16.5 to 700 microg/mL), prolonged PTT. WV (40 to 240 microg/mL) and fraction F2 (5 to 40 microg/mL), prolonged PT. No thrombin-like activity was found with this venom on human plasma or purified fibrinogen. Td venom contains procoagulant components, able to shorten PTT. In addition, the venom contains anticoagulant components which prolong PT and PTT.

Bactridine 2 effect in DRG neurons. Identification of NHE as a second target.

Bactridine 2 (Bact-2) is an antibacterial toxin from Tityus discrepans venom which modifies isoforms 1.2, 1.4 and 1.6 voltage-dependent sodium (Nav) channels. Bactridine-induced Na+ outflow in Yersinia enterocolitica was blocked by amiloride, suggesting that Bact-2 effect was mediated by an amiloride sensitive sodium channel. In this study we show that Bact-2 increases also an outward rectifying current in rat dorsal root ganglia (DRG) sensory neurons; therefore, the nature of the outward rectifying currents was characterized and then the effect of Bact-2 on these currents was studied. These currents are enhanced by amiloride, are decreased by Na+ when an outward pH gradient is present and its reversal potential coincides with that of a Cl-/H+ exchanger, suggesting that rectifying currents are produced by the electrogenic Cl-/H+ exchanger modulated by the Na+/H+ antiporter. Bact-2 also leads to an increase of the outward currents in a similar way to the produced by the inhibition of the Na+/H+ exchanger. Additionally, the subsequent application of Bact-2 after blocking the Na+/H+ exchanger does not produce any further effect, suggesting that Bact-2 modifies the outward current by modulating the activity of the Na+/H+ exchanger. The effect of Bact-2 on pHi regulation was determined using the pH indicator BCECF. The results show that the Na+/H+ exchanger is blocked by amiloride and Na+ free solutions and is modulated by Bact-2 in a similar way as cariporide. This study validates that besides Nav channels, Bact-2 modulates the activity of the Na+/H+ exchanger.

Initial volume of a drug before it reaches the volume of distribution: pharmacokinetics of F(ab')2 antivenoms and other drugs.

Fast disappearance of F(ab')2 antivenoms from the plasma compartment [Sevcik et al., 2004. Modelling Tityus scorpion venom and antivenom pharmacokinetics. Evidence of active immunoglobulin G's F(ab')2 extrusion mechanism from blood to tissues. Toxicon 44, 731-734; Vazquez et al., 2005. Pharmacokinetics of a F(ab')2 scorpion antivenom in healthy human volunteers. Toxicon 46, 797-805] suggests a quick time course to reach its final distribution volume. An equation was developed to describe how the volume occupied by a drug in the body grows with time. As discussed in the paper this equation is free of some shortcomings of an equation developed for the same purpose by Niazi [1976. Volume of distribution as a function of time. J. Pharm. Sci. 65, 452-454]. Fluorescence microscopy showed that the rapid initial decay in plasmatic F(ab')2 concentration may be related to uptake of F(ab')2 by vascular endothelium which, in combination with accumulation in the vascular wall connective tissue, may produce an intermediate plateau in F(ab')2 V(sl)(t), which reached its final value after 10 h. The V(sl)(t) equation predicts that the plasma concentration half-time of decay has little use to estimate how a drug distributes through the body to exert its action, and predicts that, in some instances, intermediate plateaus in the time course of V(sl)(t) exist. Data from the literature showed that the kinetic considerations for V(sl)(t) also apply to clevidipine, digoxin, digitoxin, lidocaine and thiopentone.

Effect of leukocyte inhibitors benzydamine and cyclophosphamide, on lung injury caused by Tityus discrepans scorpion venom.

We studied the effects of benzydamine (BZ) and cyclophosphamide (CP) on acute lung injury caused by Tityus discrepans venom. Mice (male, IVIC strain, approximately 25g) were pretreated with either BZ (20microg/g) or CP (100microg/g) i.p. or saline. Envenoming (2microg/g mouse) was induced sc. Lung fraction area occupied by fibrin (FF), nuclei (NF), alveolar space (AS) and parenchyma (PF) were determined. Venom increased FF, NF and PF, significantly, and decreased AS. BZ antagonised venom's effect on FF sharply, antagonised partially effects on PF and AS, but was not able to antagonise effect on NF. CP abolished venom effects on NF, AS and PF, but was not able to antagonise the effect on FF. CP was slightly less effective than BZ in reducing FF. Fibrin deposition was associated to leukocyte sequestration. Blocking pro-inflammatory leukocyte metabolic pathways with BZ diminished FF, suggesting that neutrophil activation, inflammation and coagulation are correlated in the genesis of scorpionism acute lung injury.

Caveat on the Boltzmann distribution function use in biology.

Sigmoid semilogarithmic functions with shape of Boltzmann equations, have become extremely popular to describe diverse biological situations. Part of the popularity is due to the easy availability of software which fits Boltzmann functions to data, without much knowledge of the fitting procedure or the statistical properties of the parameters derived from the procedure. The purpose of this paper is to explore the plasticity of the Boltzmann function to fit data, some aspects of the optimization procedure to fit the function to data and how to use this plastic function to differentiate the effect of treatment on data and to attest the statistical significance of treatment effect on the data.

Pharmacokinetics of whole IgG equine antivenom: comparison between normal and envenomed rabbits.

Pharmacokinetics of antivenoms has been mainly studied in normal animals, whereas very little is known on pharmacokinetics in envenomed animals. The aim of this study was to compare pharmacokinetic parameters of whole IgG equine antivenom in normal rabbits and in rabbits suffering a moderate envenoming by intramuscular injection of the venom of the viperid snake Bothriechis lateralis, which induces drastic microvascular alterations. Anti-Micrurus nigrocinctus antivenom was used, instead of polyvalent (Crotalinae) antivenom, to avoid the formation of toxin-antibody complexes which may alter antivenom pharmacokinetics. It was thus possible to study the effect of vascular alterations, i.e., edema and hemorrhage, induced by the venom on IgG antivenom distribution and elimination. An ELISA was utilized to quantify equine IgG antivenom concentration in rabbit serum. In addition, the amount of IgG antivenom extravasated in injected muscles was also determined. Results indicate that there were no significant differences, between control and envenomed rabbits, in any of the pharmacokinetic parameters investigated, thus suggesting that a moderate envenoming by this viperid species does not alter the pharmacokinetics of IgG antivenom. A significantly higher amount of antivenom IgG was observed in muscle from envenomed rabbits than in muscle from control animals. However, this corresponds to a low percentage of the administered antivenom and, therefore, this increased local extravasation does not have a significant impact in the overall antivenom pharmacokinetics.

Characterizing Tityus discrepans scorpion venom from a fractal perspective: Venom complexity, effects of captivity, sexual dimorphism, differences among species.

A characteristic of venom elution patterns, shared with many other complex systems, is that many their features cannot be properly described with statistical or euclidean concepts. The understanding of such systems became possible with Mandelbrot's fractal analysis. Venom elution patterns were produced using the reversed phase high performance liquid chromatography (HPLC) with 1 mg of venom. One reason for the lack of quantitative analyses of the sources of venom variability is parametrizing the venom chromatograms' complexity. We quantize this complexity by means of an algorithm which estimates the contortedness (Q) of a waveform. Fractal analysis was used to compare venoms and to measure inter- and intra-specific venom variability. We studied variations in venom complexity derived from gender, seasonal and environmental factors, duration of captivity in the laboratory, technique used to milk venom.

The indirect effect of Tityus discrepans on rabbit pulmonary vasculature.

Serum (IS) was obtained 0.5, 2, 4 or 6 h after inoculating s.c. six rabbits (approximately 2 kg) in each time period with 1 mg/kg of Tityus discrepans (Td) venom; the control was serum obtained from four rabbits 4 h after injecting them 1 ml s.c. of 0.9% NaCl. IS produced a transient (<25 min) rise in pulmonary artery pressure of isolated and perfused rabbit lungs, other lung parameters were not altered. We found that both scorpion venom and IS produced a approximately 50% transient increase of transendothelial electric resistance in cultured tissue human umbilical cord vein. Neither venom nor IS changed the transepithelial electrical resistance of tissue cultured human airway epithelia. The experiments suggest that humoral factors contained in the inoculated serum modify vascular endothelium in a much more effective manner than the venom by itself. These experiments also make it unlikely that vascular endothelium is the source of the humoral factors contained in inflammatory serum.

Macrophage alteration induced by inflammatory toxins isolated from Tityus discrepans scorpion venom. The role of Na(+)/Ca(2+) exchangers.

We study the effect of all Tityus discrepans venom components on macrophage alterations. Only seven toxins called "Inflammatory Toxin" (InfTx1-7) induced cell changes. Incubation with InfTx1 through InfTx5 rose macrophage NO level at 2 h toxin exposure. Cells rose NO release by 4 h exposure with InfTx2 and InfTx5, the NO levels reached concentrations similar or higher than the induced by lipopolysaccharides (LPS) incubation. InfTx2, -6 and -7 increased cell TNF-α release. InfTx2 as LPS roses cell TNF-α secretion gradually in time. Macrophages were loaded with fluorescent dyes, exposed to all toxins and observed with a 3D wide field deconvolution setup. Cells exposed to whole venom or InfTx4 through InfTx7 developed pseudopodia, cytoplasm prolongations, blebs, and loss their rounded form. The molecular masses and N-terminal sequences of InfTx4 through InfTx7 were analyzed by MALDI-TOF mass spectrometry and Edman degradation. InfTx4-7 induced a remarkable increase of intracellular Ca(2+) levels ([Ca(2+)]i), measured as a rise of normalized cell green fluorescence intensity (FI) ×2.7, ×2.6, ×95 and ×2.9 the controls, respectively. InfTx6-7 action mechanisms were studied under different conditions. Results suggested that InfTx6 interact with a membrane sodium channel inducing cell depolarization with a consequent increase on intracellular [Na(+)], this would activate Na(+)/Ca(2+) exchanger 3 (NCX) in the reverse mode and the phospholipase C inositol 1,4,5-trisphosphate (PLC-IP3) signaling pathway inducing [Ca(2+)]i overload. Inftx7 should activate the NCX in reverse mode and/or should activate the Na(+)/H(+) exchanger, increasing intracellular [Na(+)] which indirectly induce the activation of NCX3rv and the PLC-IP3 signaling pathway. All these mechanisms would cooperate with the [Ca(2+)]i overload. A rise of [Ca(2+)]i activates the synthesis and secretion of inflammatory molecules like TNF-α, which in turn, increases the gene transcription for inducible nitric oxide synthase, resulting on NO production.

Fibrin(ogen)olytic enzymes in scorpion (Tityus discrepans) venom.

Several fibrin(ogen)olytic enzymes from Tityus discrepans (Buthidae, Buthoidea) venom (TdV) were partially purified on a Sephadex G-50 column, by affinity and molecular exclusion high-performance chromatography. Fractions SB1-I and SB1-II had fibrinolytic, fibrinogenolytic (Aα-chains degradation) and tissue plasminogen activator (t-PA)-like activities. SB1-III was only fibrinogenolytic (fast degradation of Aα-chains and slower degradation of fibrinogen Bß-chains). These results showed the presence of α-fibrinogenases in TdV. The fibrino(geno)lytic activity in these fractions was abolished by metalloprotease inhibitors (MPI). Fractions SB3-I and SB3-II contain fibrinogenolytic (Aα-chains degradation) and fibronectinolytic activities. Also fraction SB3-I had a t-PA-like activity. Activities in SB3-I and SB3-II were abolished by serine protease inhibitors (SPI). None of the fractions degraded fibrinogen γ-chains. Fibrinogen degradation by active fractions is associated with an anticoagulant effect supported by a reduced coagulant activity. The overall outcome suggests that metalloproteases and serine proteases in TdV are responsible for fibrin(ogen)olytic activity because MPI and SPI inhibited these activities.

IgY pharmacokinetics in rabbits: implications for IgY use as antivenoms.

This paper presents the first study of chicken IgY pharmacokinetics (PK) in rabbits. We measured IgY blood serum concentrations using a specific high sensitivity ELISA method. The fast initial component observed when studying horse Fab, F(ab')2 or IgG was absent from IgY PK. During the first 80 min of observation there was only a single slow exponential decay, which sped up afterward to the point that IgY became undetectable after 216 h of observation; due to this time course, PK parameters were determined with trapezoidal integration. The most significant IgY pharmacokinetic parameters determined were (all presented as medians and their 95% confidence interval): Area Under the Curve = 183.8 (135.2, 221.5) mg·h·L(-1); Distribution volume of the central compartment·[Body Weight (BW)](-1) = 46.0 (21.7, 70.3) mL·kg(-1); Distribution volume in steady state·BW(-1) = 56.8 (44.4, 68.5) mLkg(-1); Mean Residence Time = 40.1 (33.6, 48.5) h; Total plasma clearance·BW(-1) = 1.44 (1.15, 1.66) mL·h(-1)·kg(-1). Anti IgY IgG titers determined by ELISA increased steadily after 72 h, and reached 2560 (1920, 5760) dilution(-1) at 264 h; anti-chicken IgG concentrations rose up to 3.19 (2.31, 6.17) µg/mL in 264 h. Our results show that IgY PK lacks the fast initial decay observed in other PK studies using horse IgG, F(ab')2 or Fab, remains in the body 39.0 (28.7, 47.2) % much as IgG and is ≈3 times more immunogenic that horse IgG in rabbits.

Production of anti-horse antibodies induced by IgG, F(ab')2 and Fab applied repeatedly to rabbits. Effect on antivenom pharmacokinetics.

We separated whole IgG, Fab and F(ab')2 fragments from horse plasma. We previously studied the pharmacokinetics of these immunoglobulins and fragments in rabbits and shown that Fab and F(ab')2 pharmacokinetics were well described by a three-exponential kinetics, while IgG and IgG(T) pharmacokinetics, however, deviated from the three-exponential kinetics 120 h after injecting a bolus of the immunotherapeutics; this departure was shown to be due to a surge of anti-horse antibodies occurring after 120 h, peaking at ≈260 h and decaying slowly afterward (Vázquez et al., 2010). We now describe antivenom pharmacokinetics and anti-horse IgG production in rabbits receiving three boluses (300 µg/kg, I.V.) of Fab, F(ab')2 or IgG separated by 21 days.

High resolution fluorescence microscopy evidence on the transport of immunoglobulins. Differences between mammalian IgG, F(ab')2 and avian IgY.

We describe the subcellular localization of horse F(ab')(2) and IgG, and ostrich IgY labeled with fluorescein isothiocyanate (FITC) administered IV to mice. We used wide field high sensitivity fluorescence microscopy deblurred by 3-dimensional blind deconvolution of kidney, liver, lungs and brain sections. Sections were obtained from mice sacrificed 15 min, 1 or 5 h after receiving FITC-immunoproteins, counter-stained with DAPI (4',6'-diamidino-2-phenylindole) and Evans blue. FITC-IgG and its fractions are rapidly taken up and extravasated by vascular endothelium. FITC-IgG and FITC-F(ab')(2) appear to be quickly secreted by glomeruli endothelium and to be reabsorbed along all nephron segments. FITC-IgG and FITC-F(ab')(2) appeared 15 min after IV injection within bronchial, alveolar and bile duct epithelium. Hepatocytes were loaded with fluorescence after 15 min of administration. Fluorescence was absent from brain slices, except for the endothelium of some vessels in brain ventricles which appeared intensely fluorescent. Fluorescence appeared in intracellular vesicles which conferred the tissues a glowing foamy aspect for up to 5 h after inoculation. Arterial elastic layers were intensely green after horse FITC-Ig inoculation. Ostrich FITC-IgY behaved completely differently to horse Ig's; only 1 h after injection it was possible to observe small brightly green scarce vesicles in vascular endothelium of arteries, interstitial kidney capillaries between nephron tubules and were also scarce in glomeruli endothelium; FITC-IgY appeared only in hepatic sinusoids in the liver. No IgY was seen in bronchial and alveolar endothelium, in bile ducts or in hepatocytes.

Horse IgG- and ostrich IgY-F(ab')2 groups have different affinities for mice erythrocytes and lymphocytes. Implications for avian immunoglobulin therapeutic usefulness.

We used high sensitivity and resolution fluorescence microscopy to study the interaction of ostrich IgY, horse F(ab')2 and horse IgG with mice lymphocyte and erythrocyte plasma membrane. The immunoglobulins were labeled with fluorescein isotiocyanate (FITC). Our results show an interaction of IgY with lymphocyte plasma membrane which does not result in endocytosis of the labeled protein. Less IgG and its F(ab')2 fraction bind to lymphocytes, and this binding seems to be followed by endocytosis producing a diffuse cytoplasmic fluorescence in most lymphocytes exposed to FITC-IgG or FITC-F(ab')2. Cytoplasmic fluorescence resembling FITC was not observed in lymphocytes exposed to FITC-IgY. Receptors in the erythrocyte membrane also differentiate between avian and horse Ig; while erythrocytes exposed to horse Igs became intensely fluorescent for at least 5 h, no erythrocyte labeling occurred when FITC-IgY was used. Our results suggest that IgY may be a stronger activator of adaptive immunity than horse IgG in mammals. Adaptive immunity against IgY is detrimental to its IV therapeutic use in humans and other mammals.

Subtype specificity interaction of bactridines with mammalian, insect and bacterial sodium channels under voltage clamp conditions.

The present work demonstrates that bactridines (Bacts) possess different selectivities for neuronal and muscular voltage-dependent sodium (Na(V) ) channels, with subtle differences on channel isoforms. Bacts 2, 3, 4, 5 and 6 (100 nm) reduced the peak current of several skeletal and neuronal channel isoforms selectively. Bacts 2 and 3 were more potent on Na(V) 1.4, Bacts 4 and 6 on Na(V) 1.3 and Bact 5 on Na(V) 1.7. Bactridines (except Bacts 1 and 5) caused a hyperpolarizing shift in the V(1/2) of activation and inactivation of Na(V) 1.3, Na(V) 1.4 and Na(V) 1.6. Voltage shifts of Boltzmann curves fitted to activation and inactivation occurred with a decrease in κ. Since the slope is proportional to κ = RT/zF, changes in κ probably express changes in z, the valence, in a voltage-dependent manner. Changes in z may express toxin-induced changes in the channel ionic environment, perhaps due to surface charges of the molecules. Bact 2 induced a Na(V) 1.2 voltage shift of the activation curves but no shift of the mutant Na(V) 1.2 IFM/QQQ; peak I(N) (a) was reduced in both channel forms, suggesting that channel blockage resulted from toxin binding to a site partially distinct from the α subunit binding site 4. Bactridines emerge as potential research tools to understand sodium channel isoform structure-function relationships and also as pharmacologically interesting peptides.