Search PubMed⌕ Search

Biomedical subjects

M F Martin

Publications and source records attributed to M F Martin.

At least 37 records · Page 2Linked to original sources
PubMed1986

Tityus serrulatus toxin VII bears pharmacological properties of both beta-toxin and insect toxin from scorpion venoms.

Some beta-toxins from the South American scorpion Tityus serrulatus (e.g. Ts VII) are highly toxic both for mouse and fly larva. Radioiodinated Ts VII and the insect toxin from the North African scorpion Androctonus australis Hector (AaH IT) bind to the same site on a house fly head synaptosomal fraction. These results reinforce the hypothesis about the existence of a correlated series of scorpion toxins as previously defined by amino acid compositions and sequences, and immunological and circular dichroism studies, in suggesting that Ts VII constitutes a link which may fill the pharmacological gap existing between beta-toxins and insect toxins such as AaH IT.

Animals↗
PubMed1986

Large scale purification of toxins from the venom of the scorpion Androctonus australis Hector.

A large scale procedure for purification of the toxins in the venom of the North African scorpion Androctonus australis has been developed. This procedure optimizes the sequence of the steps, leading to better yields of toxins and shortening of the time. It is possible to use 10-15 g batches of venom and also prevent cross-contamination of the toxins. High pressure liquid chromatography has been used to separate AaH I and I', two isotoxins which differ by one amino acid residue in position 17: valine or isoleucine. The procedure allows the characterization of a new toxin active in mice, AaH IV, which represents 0.6 and 2.5% of the venom weight and toxicity, respectively. This new component has been characterized as an alpha toxin made up of 61 amino acid residues and having a neutral isoelectric point.

Amino Acids↗
PubMed1985

An excitatory and a depressant insect toxin from scorpion venom both affect sodium conductance and possess a common binding site.

Two insect selective toxins were purified by gel-permeation and ion-exchange chromatographies from the venom of the scorpion, Leiurus quinquestriatus quinquestriatus, and their chemical and pharmacological properties were studied. The first toxin (LqqIT1) induces a fast excitatory contraction paralysis of fly larvae and is about 40 times more toxic than the crude venom. It is a polypeptide composed of 71 amino acids, including 8 half-cystines and devoid of methionine and tryptophan, with an estimated molecular weight of 8189 and a pI value of 8.5. The second toxin (LqqIT2) induces a slow depressant, flaccid paralysis of fly larvae. It is composed of 72 amino acids, including 8 half-cystines, is devoid of proline methionine and histidine, and has an estimated molecular weight of 7990 and a pI value of 8.3. The contrasting symptomatology of these toxins is interpreted in terms of their effects on an isolated axonal preparation of the cockroach in current and voltage clamp conditions. LqqIT1 (0.5-4 microM) induced repetitive firing of the axon which was attributable to two changes in the sodium conductance, a small increase in the peak conductance and a slowing of its turning off. LqqIT2 (1-8 microM) caused a blockage of the evoked action potentials, attributable to both a strong depolarization of the axonal membrane and a progressive suppression of the sodium current. Neither toxin affected potassium conductance. The two toxins differ mainly in their opposite effects on the activatable sodium permeability. In binding assays to a preparation of insect synaptosomal membrane vesicles, the two toxins were shown to competitively displace the radioiodinated excitatory insect toxin derived from the venom of the scorpion, Androctonus australis [( 125I]AaIT), which strongly resembles, in its chemistry and action, the LqqIT1 toxin. The present two toxins have demonstrated a strong affinity closely resembling the AaIT, with KD values of 0.4, 1.9, and 1.0 nM for LqqIT1, LqqIT2, and AaIT, respectively. These data suggest the possibility that the excitatory and depressant insect toxins share a common binding site associated with sodium channels in insect neuronal membranes.

Amino Acids↗
PubMed1985

Effect of dazoxiben, a thromboxane synthetase inhibitor on skin-blood flow following cold challenge in patients with Raynaud's phenomenon.

The effects of dazoxiben on finger-blood flow in response to cold challenge were studied in normal subjects and patients with Raynaud's phenomenon. In normal subjects concentrations of TXB2 and 6-oxo-PGF1 alpha were measured in blood taken from dorsal hand veins following cold challenge. In a parallel multicentre study we examined the effects of dazoxiben on finger temperature and capillary blood cell velocity in patients with Raynaud's phenomenon. Dazoxiben did not affect finger arterial inflow at rest or during cold challenge in patients or controls. However in both groups, recovery was quicker after cold challenge on dazoxiben treatment. In patients median flow was 5 ml (100(-1) ml) min-1 (range 1-10) v. 2 (0.5-15), P less than 0.05 dazoxiben v. placebo at 15 min after cold challenge. However, in normal subjects this did not prove to be statistically significant. In normal subjects there was a fall in TXB2 concentrations and relative rise in 6-oxo-PGF1 alpha following dazoxiben treatment indicating redirection of prostaglandin endoperoxides towards synthesis of PGI2. Comparison of the sum-total output of each eicosanoid following treatment with dazoxiben revealed a 65% reduction in TXB2 concentrations (P less than 0.025 compared with placebo) and a 40% increase in 6-oxo-PGF1 alpha concentrations (P less than 0.05 compared with placebo). However a simultaneous increase in concentrations of FPA indicated generation of thrombin, probably at the needle tip. Long-term treatment with dazoxiben resulted in no significant change in finger-skin temperature or capillary blood cell velocity, duration, or severity of attacks of Raynaud's phenomenon.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Biochemical and clinical changes occurring during the treatment of rheumatoid arthritis with novel antirheumatoid drugs.

Groups of 15 patients with active rheumatoid arthritis have been treated with sulphasalazine, (salazosulfapyridine INN), zinc sulfate, captopril or methyl cysteine, and assessed by seven clinical measurements and six laboratory methods on eight occasions during a 24-week treatment period. The results have been compared with equivalent data derived from the use of antiinflammatory agents (e.g. aspirin) and drugs of accepted 'antirheumatoid activity' (e.g. D-penicillamine). Improvements in mean data provide the basis of a human screening system for the detection of antirheumatoid drug activity. Results suggest that sulphasalazine and captopril have this type of activity whereas zinc sulfate and methyl cysteine do not.

Adult↗
PubMed1984

Amino acid sequence of toxin VII, a beta-toxin from the venom of the scorpion Tityus serrulatus.

The sequence of the 61 amino acids of toxin VII, a beta-toxin from the venom of the South American scorpion Tityus serrulatus, has been determined by automatic sequencing of the reduced and S-[14C] carboxymethylated protein and of tryptic peptides obtained before or after citraconylation of this protein. This toxin, the most active beta-toxin from this venom, is the first Tityus toxin to be fully sequenced. The results clearly show that toxin VII belongs to the structural group of scorpion toxins originating from Central and North America.

Amino Acid Sequence↗
PubMed1984

Captopril: a new treatment for rheumatoid arthritis?

Captopril, an inhibitor of angiotensin converting enzyme, is prescribed for hypertension. Its molecular structure shares features with D-penicillamine, in that both agents contain a thiol group. In addition, captopril has immunosuppressant activity. Captopril was therefore considered a potential slow-acting drug for treating rheumatoid arthritis. In an open study 15 patients with active arthritis were treated with captopril and followed for 48 weeks. Two-thirds of the patients reported improved arthritis symptoms, and significant changes were seen in several clinical and biochemical measurements, notably Ritchie articular index, clinical score, plasma viscosity, and C-reactive protein. Side-effects were generally mild and included transient taste loss, rashes, and hypotension. Only 2 patients withdrew as a result of drug intolerance.

Adult↗
PubMed1984

Purification of thirteen toxins active on mice from the venom of the North African scorpion Buthus occitanus tunetanus.

A combination of several equilibrium chromatographic steps permitted us to purify thirteen proteins from the venom of Buthus occitanus tunetanus using the mouse as the test animal for lethality measurement. These proteins have been characterized by their amino acid composition and, for seven of them, by their N-terminal or complete amino acid sequence. The structural data obtained correlate well with the pharmacological and antigenic properties of the neurotoxins.

Amino Acid Sequence↗
PubMed1984

Purification and amino acid sequence of toxin I" from the venom of the North African scorpion Androctonus australis Hector.

When a large quantity of the venom of the scorpion Androctonus australis Hector is submitted to a purification procedure it is possible to purify a new toxin, toxin I", which is lethal to mouse, and present in very low quantities. The yield is 0.04%. The amino acid sequence of this newly discovered toxin only differs from toxin I of the same scorpion by an extra arginine residue at the C-terminal end provided that the sequence of toxin I, at positions 34 and 35, is in agreement with newer information provided in this paper.

Amino Acid Sequence↗
PubMed1984

Prostaglandins cause an increase in serum acute-phase proteins in man, which is diminished in systemic sclerosis.

The prostaglandin E1 increases the plasma concentration of acute-phase proteins in man and decreases the concentration of certain carrier proteins. This response is greatly diminished in patients with systemic sclerosis, a chronic inflammatory disease leading to fibrosis. These findings pose new questions about the mediation of the acute-phase response and its role in controlling the inflammatory process.

Alprostadil↗
PubMed1984

Interaction of scorpion toxins with the sodium channel.

Scorpion toxins are miniproteins that have been characterized with regard to their molecular properties including their pharmacological action. On these bases, toxins specific to mammals or to insects have been described and within the first category alpha- and beta-toxins identified. These toxins were chemically modified and used as molecular probes of the sodium channel. Thus, the interaction of the toxins with the pharmacological target could be followed and a better definition of this target could be obtained.

Animals↗
PubMed1983

Captopril.

Explore the source record for details and available documents.

Arthritis, Rheumatoid↗
PubMed1983

The effect of drugs on serum histidine levels in rheumatoid arthritis.

Groups of 15 patients with active rheumatoid arthritis were treated for 24 weeks with zinc sulphate, trien, captopril, clozic in two doses or a combination of D-penicillamine and hydroxychloroquine. Serum histidine levels were monitored along with measures of disease activity including C-reactive protein, plasma viscosity, articular index, grip strength and early morning stiffness. Zinc sulphate and trien were found to be ineffective while the other drugs all showed evidence of second-line action. Serum histidine was found to improve during successful therapy. The possible cause of low serum histidine and its response to therapy is discussed.

Anti-Inflammatory Agents↗
PubMed1983

Immunochemistry of scorpion alpha-neurotoxins. Determination of the antigenic site number and isolation of a highly enriched antibody specific to a single antigenic site of toxin II of Androctonus australis Hector.

Scorpion neurotoxins active on mammals, i.e. alpha- and beta-toxins, have been divided into several groups according to structural and also immunological criteria. A study of the alpha-toxins has been performed in order to determine the number of antigenic sites; a minimum of four Fab fragments were found to bind simultaneously to toxins I and II of Androctonus australis Hector, and toxin I of Buthus occitanus tunetanus. Taking advantage of the loss of one common antigenic site between toxin II of Androctonus australis Hector and toxin III of Buthus occitanus tunetanus, a highly purified antibody population towards a single site of toxin II of Androctonus australis Hector was isolated and characterized. This result is discussed in terms of sequence homologies between the two proteins as the amino acid sequence of toxin III of Buthus occitanus tunetanus has been determined using standard procedures: the two proteins differ at three positions, two of which (positions 10 and 64) are in the vicinity of the disulfide bridge Cys 12-Cys 63, the third (position 51) is the only one to be conservative.

Amino Acid Sequence↗
PubMed1983

A comparison of platelet count and acute phase proteins in the measurement of disease activity in rheumatoid arthritis.

Platelet count (PC) was compared with standard acute phase reactants (ESR, plasma viscosity and C-reactive protein) and clinical measurements to assess its usefulness as a measure of disease activity in 165 patients with active rheumatoid arthritis. Although PC was elevated (greater than 400 X 10(9) 1(-1) in 45% of patients and was seen to fall under the influence of second-line drugs, it was considered to be unsuitable as an indication of disease activity since levels fall for reasons other than disease improvement.

Anti-Inflammatory Agents↗
PubMed1983

Gangrene developing after minor surgery in a patient with undiagnosed systemic lupus erythematosus and lupus anticoagulant.

We report a case of progressive peripheral ischaemia and gangrene as a presenting feature of systemic lupus erythematosus. It developed in a previously asymptomatic 40-year-old woman following minor surgery to her toe. Eventually she required a below-knee amputation and despite systemic corticosteroids continued to deteriorate, presenting later with signs of systemic intravascular thromboses. Histopathology and immunofluorescence on vessels repeatedly failed to demonstrate any evidence for vasculitis. A full coagulation screen confirmed the presence of 'lupus' anticoagulant. A plasma exchange was performed to remove circulating immunoglobins and she made a rapid and sustained recovery. Peripheral gangrene has not previously been described in association with lupus anticoagulant. We would suggest that in all cases of systemic thrombosis or unexplained peripheral vascular ischaemia lupus anticoagulant should be considered.

Adult↗
PubMed1982

Effects of prostaglandin E1 on microvascular haemodynamics in progressive systemic sclerosis.

The effects of prostaglandin E1 infusion on nailfold capillary haemodynamics were studied in eight patients with Raynaud's phenomenon secondary to progressive systemic sclerosis. Using a modified Landis microinjection technique the mean (+/- SEM) transcapillary pressure gradient was increased during and six weeks after infusion by 13.9 +/- 3.2 cm H2O (p less than 0.05) and 5.5 +/- 2.5 cm H2O (p less than 0.05) respectively. Capillary red cell velocity measured in two patients by video television microscopy also increased during and after infusion with prostaglandin E1. Six patients claimed subjective benefit and in three their ulcers healed. These findings support the observed beneficial effect of prostaglandin E1 and suggest that it improves the nutritive capillary circulation by lowering precapillary resistance.

Adult↗