Sigmoid semilogarithmic functions with shape of Boltzmann equations, have become extremely popula... more 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.
... Drs. Alejandro Guinand, Hernando Cortés, Gina D´Suze, Patricia Díaz, Carlos Sevcik ... 16. D´... more ... Drs. Alejandro Guinand, Hernando Cortés, Gina D´Suze, Patricia Díaz, Carlos Sevcik ... 16. D´Suze G, Moncada S, González C, Sevcik C, Aguilar V, Alagón A. Los pacientes de escorpionismo con sintomatología local tienen niveles importantes de veneno en plasma. ...
An important problem of optimization analysis surges when parameters such as → {θ} j j=1, ...,k ,... more An important problem of optimization analysis surges when parameters such as → {θ} j j=1, ...,k , determining a function y = f (x → {θ} j j=1, ...,k), must be estimated from a set of observables {x i , y i } i=1, ... ,m. Where {x i } are independent variables assumed to be uncertainty-free. It is known that analytical solutions are possible if y = f (x θ j) is a linear combination of { → θ j=1, ... ,k }. Here it is proposed that determining the uncertainty of parameters that are not linearly independent may be achieved from derivatives ∂f (x { → θ j }) ∂θ j at an optimum, if the parameters are stochastically independent.
E. JAIL, M. ErsIG and C. Ssvt,Llc. Effect of a toxin isolated from the sponge Haliclona viridis o... more E. JAIL, M. ErsIG and C. Ssvt,Llc. Effect of a toxin isolated from the sponge Haliclona viridis on the release of y-aminobutyric acid from rat olfactory bulb. Toxicon 31, 385-396, 1993.-A partially purified toxin from the marine sponge Hallclona viridis was studied for its effect on the presynaptic release mechanism of 3H-y-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 present study, the toxin induced a reversible release of 3H-y-aminobutyric acid in the external plexiform layer. This effect was similar to that induced by 25 mM K+. The toxin-induced outflow of 3H-y-aminobutyric acid was concentration dependent. The action of the toxin was specific for y-sminobutyric acid secretion from the external plexiform layer, and dopamine liberation from the frontal cortex; the toxin did not release 3H-valine, a non-neurotransmitter amino acid, from the external plexiform layer. Toxin-and high K+-induced neurotransmitter release were both drastically reduced when Cat+ was removed from the saline. The addition of 0.3 pIVI tetrodotoxin or the removal of Na+ from the saline did not reduce the toxin's ability to release neurotransmitters. The effect of toxin was enhanced by the addition of valinomycin. Although Haliclona toxin and 4aminopyridine induced the release of neurotransmitters, they antagonized each other's effect on y-aminobutyric acid secretion when added simultaneously .
The action of ketamine (50 microM) and 4-aminopyridine (4-AP) (50 microM) on the frog (Hyla crepi... more 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 other investigators. However, novel effects of the drugs on postsynaptic acetylcholine receptors were detected when miniature end plate potential (MEPP) amplitude and time-course were analyzed. The experiments were performed and registered in presence of 1% dimethylsulfoxide to augment frequency of MEPP's. When ketamine was added to the saline solution, MEPP amplitude control values were reduced from 226 (214, 240) microV (n = 529, median and its 95% confidence interval) to 140 (130, 151) microV (n = 143) by 50 microM ketamine. 4-AP alone also depressed MEPP amplitude to 129 (70, 152) microV (n = 91). The two drugs are partial antagoni...
Modelling Tityus scorpion venom and antivenom pharmacokinetics. Evidence of active immunoglobulin... more 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 (venenemia) was determined by enzyme-linked immunosorbent assay (ELISA) from 0 to 300 min after injecting venom. Venenemia was fit to a three-compartment model (inoculation site, plasma and extra vascular extracellular space), it was assumed that the venom may also be irreversibly removed from plasma. Calculated time course of venom content shows that at any time no more that 30% of the venom is present in plasma. Venenemia peaks at 1h and decays afterwards. Fluorescently labelled antivenom [horse anti-TityusF(ab')(2) or fraction antigen binding, immuglobulin without Fc chain covalently bound to fluorescine or fluorescamine] pharmacokinetics was determined. Although F(ab')(2) molecular weight is >/=10 times bigger that toxin's, the rate of outflow of F(ab')(2) from blood to tissues was approximately 4 times faster than the venom's outflow. Venom content in the injection site decays exponentially for >6h, this prediction was confirmed immunohistochemically. Only approximately 5% of the venom is eliminated in 10h; approximately 80% of the venom is in the tissues after 2h and remains there for >10h.
Sigmoid semilogarithmic functions with shape of Boltzmann equations, have become extremely popula... more 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.
... Drs. Alejandro Guinand, Hernando Cortés, Gina D´Suze, Patricia Díaz, Carlos Sevcik ... 16. D´... more ... Drs. Alejandro Guinand, Hernando Cortés, Gina D´Suze, Patricia Díaz, Carlos Sevcik ... 16. D´Suze G, Moncada S, González C, Sevcik C, Aguilar V, Alagón A. Los pacientes de escorpionismo con sintomatología local tienen niveles importantes de veneno en plasma. ...
An important problem of optimization analysis surges when parameters such as → {θ} j j=1, ...,k ,... more An important problem of optimization analysis surges when parameters such as → {θ} j j=1, ...,k , determining a function y = f (x → {θ} j j=1, ...,k), must be estimated from a set of observables {x i , y i } i=1, ... ,m. Where {x i } are independent variables assumed to be uncertainty-free. It is known that analytical solutions are possible if y = f (x θ j) is a linear combination of { → θ j=1, ... ,k }. Here it is proposed that determining the uncertainty of parameters that are not linearly independent may be achieved from derivatives ∂f (x { → θ j }) ∂θ j at an optimum, if the parameters are stochastically independent.
E. JAIL, M. ErsIG and C. Ssvt,Llc. Effect of a toxin isolated from the sponge Haliclona viridis o... more E. JAIL, M. ErsIG and C. Ssvt,Llc. Effect of a toxin isolated from the sponge Haliclona viridis on the release of y-aminobutyric acid from rat olfactory bulb. Toxicon 31, 385-396, 1993.-A partially purified toxin from the marine sponge Hallclona viridis was studied for its effect on the presynaptic release mechanism of 3H-y-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 present study, the toxin induced a reversible release of 3H-y-aminobutyric acid in the external plexiform layer. This effect was similar to that induced by 25 mM K+. The toxin-induced outflow of 3H-y-aminobutyric acid was concentration dependent. The action of the toxin was specific for y-sminobutyric acid secretion from the external plexiform layer, and dopamine liberation from the frontal cortex; the toxin did not release 3H-valine, a non-neurotransmitter amino acid, from the external plexiform layer. Toxin-and high K+-induced neurotransmitter release were both drastically reduced when Cat+ was removed from the saline. The addition of 0.3 pIVI tetrodotoxin or the removal of Na+ from the saline did not reduce the toxin's ability to release neurotransmitters. The effect of toxin was enhanced by the addition of valinomycin. Although Haliclona toxin and 4aminopyridine induced the release of neurotransmitters, they antagonized each other's effect on y-aminobutyric acid secretion when added simultaneously .
The action of ketamine (50 microM) and 4-aminopyridine (4-AP) (50 microM) on the frog (Hyla crepi... more 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 other investigators. However, novel effects of the drugs on postsynaptic acetylcholine receptors were detected when miniature end plate potential (MEPP) amplitude and time-course were analyzed. The experiments were performed and registered in presence of 1% dimethylsulfoxide to augment frequency of MEPP's. When ketamine was added to the saline solution, MEPP amplitude control values were reduced from 226 (214, 240) microV (n = 529, median and its 95% confidence interval) to 140 (130, 151) microV (n = 143) by 50 microM ketamine. 4-AP alone also depressed MEPP amplitude to 129 (70, 152) microV (n = 91). The two drugs are partial antagoni...
It is well known that scorpion venom induces lung lesions and respiratory distress which are usua... more It is well known that scorpion venom induces lung lesions and respiratory distress which are usually classi®ed 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 whole rabbits and on their isolated lungs perfused with Krebs saline with 1 g/l of bovine serum albumin (Krebs±BSA saline). Two milligram of venom were diluted in 250 ml of solution (Ithe rabbit's total blood volume) and used to perfuse isolated lungs. Lung oedema occurred in rabbits which received 1 mg/kg of scorpion venom i.p., heparin prevented the production of this lung oedema. T. discrepans venom produced PO, in rabbits pretreated with 15 mg/kg of ajoene. Yet, Tityus venom had no eects on isolated lungs perfused with citrated or heparinized blood, and in lungs perfused with Krebs±BSA with normal Ca 2+. These result show that Tityus venom does not act directly on lungs. Otherwise, we have observed that abundant microthrombi occurred in all rabbit lungs exposed to venom in vivo, suggesting that these cloting alterations are fundamental to produce PO. The presence of intravascular microthrombi is not characteristic of the usual PO hinting that scorpion venom induced pulmonary alterations are a dierent clinical entity. We thus propose that the use of the term pulmonary oedema in scorpionism should abandoned in favor of scorpion venom respiratory distress syndrome.
Sigmoid semilogarithmic functions with shape of Boltzmann equations, have become extremely popula... more 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.
... Drs. Alejandro Guinand, Hernando Cortés, Gina D´Suze, Patricia Díaz, Carlos Sevcik ... 16. D´... more ... Drs. Alejandro Guinand, Hernando Cortés, Gina D´Suze, Patricia Díaz, Carlos Sevcik ... 16. D´Suze G, Moncada S, González C, Sevcik C, Aguilar V, Alagón A. Los pacientes de escorpionismo con sintomatología local tienen niveles importantes de veneno en plasma. ...
An important problem of optimization analysis surges when parameters such as → {θ} j j=1, ...,k ,... more An important problem of optimization analysis surges when parameters such as → {θ} j j=1, ...,k , determining a function y = f (x → {θ} j j=1, ...,k), must be estimated from a set of observables {x i , y i } i=1, ... ,m. Where {x i } are independent variables assumed to be uncertainty-free. It is known that analytical solutions are possible if y = f (x θ j) is a linear combination of { → θ j=1, ... ,k }. Here it is proposed that determining the uncertainty of parameters that are not linearly independent may be achieved from derivatives ∂f (x { → θ j }) ∂θ j at an optimum, if the parameters are stochastically independent.
E. JAIL, M. ErsIG and C. Ssvt,Llc. Effect of a toxin isolated from the sponge Haliclona viridis o... more E. JAIL, M. ErsIG and C. Ssvt,Llc. Effect of a toxin isolated from the sponge Haliclona viridis on the release of y-aminobutyric acid from rat olfactory bulb. Toxicon 31, 385-396, 1993.-A partially purified toxin from the marine sponge Hallclona viridis was studied for its effect on the presynaptic release mechanism of 3H-y-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 present study, the toxin induced a reversible release of 3H-y-aminobutyric acid in the external plexiform layer. This effect was similar to that induced by 25 mM K+. The toxin-induced outflow of 3H-y-aminobutyric acid was concentration dependent. The action of the toxin was specific for y-sminobutyric acid secretion from the external plexiform layer, and dopamine liberation from the frontal cortex; the toxin did not release 3H-valine, a non-neurotransmitter amino acid, from the external plexiform layer. Toxin-and high K+-induced neurotransmitter release were both drastically reduced when Cat+ was removed from the saline. The addition of 0.3 pIVI tetrodotoxin or the removal of Na+ from the saline did not reduce the toxin's ability to release neurotransmitters. The effect of toxin was enhanced by the addition of valinomycin. Although Haliclona toxin and 4aminopyridine induced the release of neurotransmitters, they antagonized each other's effect on y-aminobutyric acid secretion when added simultaneously .
The action of ketamine (50 microM) and 4-aminopyridine (4-AP) (50 microM) on the frog (Hyla crepi... more 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 other investigators. However, novel effects of the drugs on postsynaptic acetylcholine receptors were detected when miniature end plate potential (MEPP) amplitude and time-course were analyzed. The experiments were performed and registered in presence of 1% dimethylsulfoxide to augment frequency of MEPP's. When ketamine was added to the saline solution, MEPP amplitude control values were reduced from 226 (214, 240) microV (n = 529, median and its 95% confidence interval) to 140 (130, 151) microV (n = 143) by 50 microM ketamine. 4-AP alone also depressed MEPP amplitude to 129 (70, 152) microV (n = 91). The two drugs are partial antagoni...
Modelling Tityus scorpion venom and antivenom pharmacokinetics. Evidence of active immunoglobulin... more 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 (venenemia) was determined by enzyme-linked immunosorbent assay (ELISA) from 0 to 300 min after injecting venom. Venenemia was fit to a three-compartment model (inoculation site, plasma and extra vascular extracellular space), it was assumed that the venom may also be irreversibly removed from plasma. Calculated time course of venom content shows that at any time no more that 30% of the venom is present in plasma. Venenemia peaks at 1h and decays afterwards. Fluorescently labelled antivenom [horse anti-TityusF(ab')(2) or fraction antigen binding, immuglobulin without Fc chain covalently bound to fluorescine or fluorescamine] pharmacokinetics was determined. Although F(ab')(2) molecular weight is >/=10 times bigger that toxin's, the rate of outflow of F(ab')(2) from blood to tissues was approximately 4 times faster than the venom's outflow. Venom content in the injection site decays exponentially for >6h, this prediction was confirmed immunohistochemically. Only approximately 5% of the venom is eliminated in 10h; approximately 80% of the venom is in the tissues after 2h and remains there for >10h.
Sigmoid semilogarithmic functions with shape of Boltzmann equations, have become extremely popula... more 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.
... Drs. Alejandro Guinand, Hernando Cortés, Gina D´Suze, Patricia Díaz, Carlos Sevcik ... 16. D´... more ... Drs. Alejandro Guinand, Hernando Cortés, Gina D´Suze, Patricia Díaz, Carlos Sevcik ... 16. D´Suze G, Moncada S, González C, Sevcik C, Aguilar V, Alagón A. Los pacientes de escorpionismo con sintomatología local tienen niveles importantes de veneno en plasma. ...
An important problem of optimization analysis surges when parameters such as → {θ} j j=1, ...,k ,... more An important problem of optimization analysis surges when parameters such as → {θ} j j=1, ...,k , determining a function y = f (x → {θ} j j=1, ...,k), must be estimated from a set of observables {x i , y i } i=1, ... ,m. Where {x i } are independent variables assumed to be uncertainty-free. It is known that analytical solutions are possible if y = f (x θ j) is a linear combination of { → θ j=1, ... ,k }. Here it is proposed that determining the uncertainty of parameters that are not linearly independent may be achieved from derivatives ∂f (x { → θ j }) ∂θ j at an optimum, if the parameters are stochastically independent.
E. JAIL, M. ErsIG and C. Ssvt,Llc. Effect of a toxin isolated from the sponge Haliclona viridis o... more E. JAIL, M. ErsIG and C. Ssvt,Llc. Effect of a toxin isolated from the sponge Haliclona viridis on the release of y-aminobutyric acid from rat olfactory bulb. Toxicon 31, 385-396, 1993.-A partially purified toxin from the marine sponge Hallclona viridis was studied for its effect on the presynaptic release mechanism of 3H-y-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 present study, the toxin induced a reversible release of 3H-y-aminobutyric acid in the external plexiform layer. This effect was similar to that induced by 25 mM K+. The toxin-induced outflow of 3H-y-aminobutyric acid was concentration dependent. The action of the toxin was specific for y-sminobutyric acid secretion from the external plexiform layer, and dopamine liberation from the frontal cortex; the toxin did not release 3H-valine, a non-neurotransmitter amino acid, from the external plexiform layer. Toxin-and high K+-induced neurotransmitter release were both drastically reduced when Cat+ was removed from the saline. The addition of 0.3 pIVI tetrodotoxin or the removal of Na+ from the saline did not reduce the toxin's ability to release neurotransmitters. The effect of toxin was enhanced by the addition of valinomycin. Although Haliclona toxin and 4aminopyridine induced the release of neurotransmitters, they antagonized each other's effect on y-aminobutyric acid secretion when added simultaneously .
The action of ketamine (50 microM) and 4-aminopyridine (4-AP) (50 microM) on the frog (Hyla crepi... more 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 other investigators. However, novel effects of the drugs on postsynaptic acetylcholine receptors were detected when miniature end plate potential (MEPP) amplitude and time-course were analyzed. The experiments were performed and registered in presence of 1% dimethylsulfoxide to augment frequency of MEPP's. When ketamine was added to the saline solution, MEPP amplitude control values were reduced from 226 (214, 240) microV (n = 529, median and its 95% confidence interval) to 140 (130, 151) microV (n = 143) by 50 microM ketamine. 4-AP alone also depressed MEPP amplitude to 129 (70, 152) microV (n = 91). The two drugs are partial antagoni...
It is well known that scorpion venom induces lung lesions and respiratory distress which are usua... more It is well known that scorpion venom induces lung lesions and respiratory distress which are usually classi®ed 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 whole rabbits and on their isolated lungs perfused with Krebs saline with 1 g/l of bovine serum albumin (Krebs±BSA saline). Two milligram of venom were diluted in 250 ml of solution (Ithe rabbit's total blood volume) and used to perfuse isolated lungs. Lung oedema occurred in rabbits which received 1 mg/kg of scorpion venom i.p., heparin prevented the production of this lung oedema. T. discrepans venom produced PO, in rabbits pretreated with 15 mg/kg of ajoene. Yet, Tityus venom had no eects on isolated lungs perfused with citrated or heparinized blood, and in lungs perfused with Krebs±BSA with normal Ca 2+. These result show that Tityus venom does not act directly on lungs. Otherwise, we have observed that abundant microthrombi occurred in all rabbit lungs exposed to venom in vivo, suggesting that these cloting alterations are fundamental to produce PO. The presence of intravascular microthrombi is not characteristic of the usual PO hinting that scorpion venom induced pulmonary alterations are a dierent clinical entity. We thus propose that the use of the term pulmonary oedema in scorpionism should abandoned in favor of scorpion venom respiratory distress syndrome.
La Fuenfría Hospital (LFH) operative parameters such as: hospitalised patients; daily admissions ... more La Fuenfría 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 variations. Conventional statistical analyses and fractal dimension analyses were performed on the series. Statistical analyses indicated that the data did not follow a Gauss (i.e. 'normal') distribution, thus nonparametric statistical analyses were chosen to describe data. The sequence of daily admitted admissions and patients staying on each service were found to be a kind of random series of a kind called random walks (Rw). Rw, sequences where what happens next, depends on what happens now plus a random variable. Rw analysed 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 factor determining LFH Rw were found to be the difference between daily admissions and discharges. The analysis suggests discharges are replaced by admissions with some random delay and that the random difference determinates LFH Rw s. The daily difference between hospitalised patients follows the same statistical distribution as the daily difference between admissions and discharges. These suggest that if the daily difference between admissions and discharges is minimised, i.e., a patient is admitted without delay when another is discharged, the number of inpatients would fluctuate less and the number of unoccupied beds would be reduced optimising the Hospital service.
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