Carlos Sevcik

Venezuelan Institute for Scientific Research | IVIC · Centro de Biofísica y Bioquímica (CBB)

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 dail...

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 oft...

La Fuenfr\'ia Hospital (LFH) operative parameters such as: hospitalised patients; daily admissions and discharges were studies for the hospital as a whole, and per each Hospital's service unit (just called "service" here). Data were used to build operative parameter value series and their variation. Conventional statistical analyses and fractal dim...

A new method to estimate parameter uncertainty in nonlinear regression analysis

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...

An important problem of optimization analysis surges when parameters such as $ \{\theta_i\}_{i=1,\, \dots \,,k }$, determining a function $ y=f(x | \{\theta_i\}) $, must be estimated from a set of observables $ \{ x_j,y_j\}_{j=1,\, \dots \,,m} $. Where $ \{x_i\} $ are independent variables assumed to be uncertainty-free. It is known that analytical...

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 avail- ability of software which fits Boltzmann functions to data, without much knowledge of the fitting procedure or the statistical properties of the parameters der...

\pi$, the ratio between a circumference and is radius, is an irrational transcendental number. Fractal analysis is used here to show that $\pi$ digit sequence corresponds to a uniformly distributed random succession of independent decimal digits, and that this propertie gets clearer as the number of digits in the series approaches infinity. This in...

This work reports a new approach to clone active Neopladine 2 (Neo2), an anticancer peptide from Tityus discrepans scorpion venom. RNA was extracted from the venom gland and cDNA was obtained by RT-PCR using complementary primers for the nucleotide sequence coding native Neo2 (nNeo2) N-terminal. Deduced amino acid sequence shows that Neo2 is compri...

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 liqui...

The development of enzyme-linked immunosorbent assays (ELISA) for venoms and antivenoms with high sensitivity has enabled to characterize pharmacokinetics (PK) of venoms and antivenoms, which in turn allowed modeling their absorption, distribution, and elimination, as well as the adequacy of different therapeutic regimes. Pharmacokinetics is the br...

All 54 recognized Tityus species in Venezuela are located at the mountain ranges, from sea level to 2,000 m above sea level, with rain forest as predom- inant habitat. The species comprised in Tityus genus are considered dangerous to humans, with similar LD 50 among their venoms. Scorpionism is endemic coinciding with the rainy season. Its characte...

A mixture of long-chain acyl polyamines (baptized as cinachyramides) was isolated from the marine sponge Cinachyrella kuekenthali, with a yield of 4.24% from the crude extract. The mixture of cinachyramides exhibited an antibacterial activity that was more pronounced against Gram positive bacteria with half lethal concentration (LC50) values of 2.5...

Venoms are complex mixtures of biologically active compounds. Their use in traditional medicine since remote times has encouraged their ex-haustive study. In this chapter the techniques used for the separation of venoms, for the study of their biological activity and the production of IgY antibodies against them are presented. We describe methods f...

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 expone...

Anti-T. discrepans F(ab')2 ELISA recognition of T. discrepans toxins was measured with regression analysis and its slope called ELISA recognition value (ERv). Fractions containing toxins affecting mammal macrophages or Na(+)-channels have Ervs > 19. Toxins affecting potassium channels or insect NaV channels have ERvs <10. Fractions including curari...

The development of enzyme-linked immunosorbent assays (ELISA) for venoms and antivenoms with high sensitivity has enabled to characterize pharmacokinetics (PK) of venoms and antivenoms, which in turn allowed modeling their absorption, distribution, and elimination, as well as the adequacy of different therapeutic regimes. Pharmacokinetics is the br...

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 concentratio...

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 activit...

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 was well described by a three-exponential kinetics, while IgG and IgG(T) pharmacokinetics, however, deviated from the three-exponetial kinet...

All 54 recognized Tityus species in Venezuela are located at the mountain ranges, from sea level to 2,000 m above sea level, with rain forest as predominant habitat. The species comprised in Tityus genus are considered dangerous to humans, with similar LD50 among their venoms. Scorpionism is endemic coinciding with the rainy season. Its character i...

We describe the sub cellular 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 sacrific...

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 pote...

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 res...

Seven toxins (F1-F7) were purified from Tityus discrepans scorpion venom on a C18 HPLC column. The compounds were fungitoxic on Macrophomina phaseolina. The molecular masses of F1-F7 were (Da) 1061.1, 7328.8, 7288.3, 7268.5, 7104.6, 6924.6, and 6823.3, respectively. It is not known if F1 is a small peptide or some other kind of organic molecule. Co...

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...

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 recu...

This paper presents the first study of F(ab')(2) scorpion antivenom pharmacokinetics in humans after intramuscular (im) administration. The specific anti-Centruroides scorpion antivenom was used in 6 human healthy volunteers. The fabotherapeutic was administered as a 47.5mg im bolus. Blood samples were drawn at 0, 5, 15, 30, 45, 60 , 90, 120, and 1...

Two novel peptides named neopladine 1 and neopladine 2 were purified from Tityus discrepans scorpion venom and found to be active on human breast carcinoma SKBR3 cells. Mass spectrometry molecular masses of neopladine 1 and 2 were 29918 and 30388 Da, respectively. Their N-terminal sequences were determined by Edman degradation. The peptides induced...

We describe the separation of whole IgG, IgG(T)-less IgG (called here merely IgG) and IgG(T) and the production of Fab and F(ab')(2) fragments. We studied the pharmacokinetics of these immunoglobulins and fragments in rabbits. Both, the isotypes and the whole IgG fragments were purified and/or produced from the same plasma lot from horses hyper imm...

I derive a method for calculating the approximate fractal dimension (D) from a set of N values y i sampled from a waveform between time zero and t max with sampling interval. The waveform is subjected to a double linear transformation that maps it into a unit square. The normalized abscissa of the square is x i * and the normalized ordinate is y i...

Six novel peptides (named bactridines) were isolated from Tityus discrepans scorpion venom. From mass spectrometry molecular masses were 6916, 7362, 7226, 7011, 7101 and 7173 Da (bactridines 1-6). Bactridines 1 and 2 were sequenced by Edman degradation. The sequences and in silico analysis, indicated that they are positively charged polypeptides co...

Tityus discrepans is a Venezuelan scorpion known to cause severe human envenomations. It contains toxins that impair proper ion channels function, affect coagulation pathways and interfere with the immunological system, leading to a widespread inflammatory syndrome. This communication reports the results of genes cloned from a cDNA expression libra...

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...

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 sa...

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),...

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 hum...

Venoms of 15 scorpion species from Venezuela and one from Brazil were compared in their antigenic cross-reactivity with specific F(ab')2 against Tityus discrepans (Td-antibodies), using the method of King and collaborators (1. King TP, Joslyn A, Kochoumian MS. Antigenic cross-reactivity of venom proteins from hornets, wasps, and yellow jackets. J A...

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...

The Venezuelan scorpion Tityus discrepans is known to cause human fatalities. We describe the first complete proteomic analysis of its venom. By HPLC 58 different fractions were obtained and 205 different components were identified by MS analysis. Components having molecular masses from 272 to 57 908 amu were found. Forty homogeneous components had...

A method was proposed by Katz in the year 1988, which implies that the fractal dimensions of a waveform might be measured by sampling N points evenly spaced on the abscissa. A similar approach was proposed by Sevcik, which shows that the approximate fractal dimension might be estimated from a set of N values y1 sampled from a waveform between time...

This paper presents the first study of F(ab')2 scorpion antivenom pharmacokinetics in humans. We have studied the pharmacokinetics of an antiscorpion venom preparation (Alacramyn) in eight human healthy volunteers. The fabotherapic was administered as a 47.5 mg i.v. bolus. Blood samples were drawn at 0, 5, 15, 30, 45, 60, 90, 120, 180 and 360 min a...

Venom was milked by gently pressing the base of the opercular and dorsal fin spines. Three fractions were obtained by molecular exclusion high pressure liquid chromatography (HPLC) (Protein Pak 125SW, Millipore Corporation) column, but only the last one with 22.7 min retention time (rt) was biological active (TmPP-22.7). This fraction was rechromat...

Anesthetized rams envenomed s.c. with 40 microg/kg Tityus discrepans scorpion venom developed fasciculation, hypothermia, polyuria, pulmonary wet rales, tachypnea, respiratory distress and arrhythmia. Rams developed a cascade of inflammation reactions, characterized by activation of macrophages, fibroblasts and neutrophils, neutrophil infiltration...

Modelling Tityus scorpion venom and antivenom pharmacokinetics. Evidence of active immunoglobulin G's F(ab')(2) extrusion mechanism from blood to tissues. We measured pharmacokinetic parameters for T. discrepans venom in rams. Forty, 75 or 100 microg/kg venom were injected subcutaneously in the inner side of the thigh. Plasma venom content (venenem...

A new peptide was purified from the venom of the Venezuelan scorpion Tityus discrepans, by high-performance liquid chromatography and its amino acid sequence was completed by Edman degradation and mass spectrometry analysis. It contains 38 amino acid residues with a molecular weight of 4177.7 atomic mass units, tightly folded by three disulfide bri...

A new arthropod selective toxin was purified from the venom of the Venezuelan scorpion Tityus discrepans, and its amino acid sequence, cDNA clone and biological activity are reported here. The amino acid sequence of this peptide, named ardiscretin (from arthropod toxin of T. discrepans) was completed by Edman degradation and mass spectrometry. It i...

We have previously shown that a paralytic toxin able to block sodium channels in nerve is associated with a cattle disease known as bovine paraplegic syndrome (BPS) [Toxicon. 31 (1993) 1581]. We have now identified this as saxitoxin (STX) using HPLC by either the methods of [Toxicon. 31 (1993) 1581], or [Toxicon. 25 (1987) 1105]. In recent experime...

A sandwich enzyme-linked immunosorbent assay was developed for measuring Tityus venom levels in plasma. The method proved capable of distinguishing patients with only local symptoms from controls, and was used to quantify venom in 205 accidental human envenomations. Our results show that the severity of envenoming is related to the patient plasma v...

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 perfu...

αα α α and nitrous oxide in 96 pediatric patients. We also found a positive correlation

Two new species of the Tityus genus are described. T. isabelceciliae n. sp lives on the northern central slope of the Cordillera de la Costa. It belongs to the discrepans group and is dangerous to man due to its high number, aggressive behavior, domiciliary habits, and high toxicity of its venom. T. isabelceciliae venom is similar to other Tityus i...

It is well known that scorpion venom induces lung lesions and respiratory distress which are usually classified as pulmonary oedema (PO). Tityus discrepans is a scorpion that lives in the north-central area of Venezuela, is the most common source of human envenomation here and produces PO. We studied the action of the venom of Tityus discrepans on...

The pure TdI-1 polypeptide that blocks miniature endplate potentials (MEPPs) and abolishes or reduces endplate potentials (EPPs) below the action potential threshold was identified from the crude fraction of Tityus discrepans venom. The toxin is a potent reversible non-depolarizing muscle relaxant that blocks more than 95% of the EPP at a 2 microM...

A characteristic of the bovine paraplegic syndrome (BPS) is ventral or sternal decubitus in animals that make unsuccessful efforts to stand when stimulated. Death occurs after a few days. In a previous work we showed the existence of a sodium channel blocking toxin (SCBT) produced by ruminal bacteria in cattle with or liable to develop BPS. The pre...

Tityus discrepans venom was fractionated by gel filtration on Sephadex G-50 column. The peptides in fraction II from Sephadex were further purified by high performance liquid chromatography, through a C4 reverse-phase column. Lethality of purified peptides was determined by injection into mice and crabs, and their effects were verified electrophysi...

Four toxic polypeptidic fractions (TdF-I-IV) were purified from the venom of the Venezuelan scorpion Tityus discrepans by means of gel filtration on Sephadex G'-50. The peptides have mol. wts of approx. 6000 and normalized elution volumes (Vn = Elution volume/Total column volume) of: TdF-I = 0.27 (0.26, 0.28), n = 13; TdF-II = 0.40 (0.39, 0.41), n...

The action of partially purified HvTX, toxin of the marine sponge H. viridis, was explored on the giant axon of the tropical squids Doryteuthis plei and Sepioteuthis sepioidea. HvTX depolarizes the nerves dose dependently. The effect occurs after blocking sodium channels with tetrodoxin (1 microM), removing external Na+, blocking electrically excit...

A clinical entity named 'bovine paraplegic syndrome' ('síndrome parapléjico de los bovinos') has spread alarmingly in the cattle-growing areas of the central and eastern plains of Venezuela. It is estimated that four million cattle are bred in the area where the disease occurs. The mortality ranges from 5 to 25% of the animals at risk, mostly pregn...

We studied the ruminal population densities of bacteria in animals with and without bovine paraplegic syndrome (BPS). All bacterial counts were performed under strict anaerobiosis. Although the rumen bacterial density was around 10(9) bacteria/ml in animals, both apparently healthy or suffering from BPS, a shift towards Gram-negative strains occurr...

A clinical entity named ‘bovine paraplegic syndrome’ (‘síndrome paraple´jico de los bovinos’) has spread alarmingly in the cattle-growing areas of the central and eastern plains of Venezuela. It is estimated that four million cattle are bred in the area where the disease occurs. The mortality ranges from 5 to 25% of the animals at risk, mostly preg...

A partially purified toxin from the marine sponge Haliclona viridis was studied for its effect on the presynaptic release mechanism of 3H-gamma-aminobutyric acid from nerve terminals of the external plexiform layer of rat olfactory bulb. Previously, the toxin of H. viridis was shown to block the resting potassium conductance in frog muscle. In the...

A clinical entity named "Bovine Paraplegic Syndrome" ("Síndrome Parapléjico de los Bovinos") has spread alarmingly, in the cattle growing areas of the central and eastern plains of Venezuela. Approximately four million cattle are bread in the area were the disease occurs. The mortality index due to the disease ranges 5 to 25% of the animals at risk...

The action of ketamine (50 microM) and 4-aminopyridine (4-AP) (50 microM) on the frog (Hyla crepitans) neuromuscular junction using standard intracellular recording techniques was investigated. In our experiments the amplitude of evoked end plate potential was decreased by ketamine and increased by 4-AP, which is similar to the effects reported by...

We developed and tested two new procedures to find which species present in samples of phytoplankton is responsible for the production of a toxin. The procedures represent a different form of correlation analysis that uses information on the presence or absence of the toxin, and on the relative abundance of each species of plankton in the samples....