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Biomedical subjects

P Gopalakrishnakone

Publications and source records attributed to P Gopalakrishnakone.

At least 73 records · Page 4Linked to original sources
PubMed1995

A novel analgesic toxin (hannalgesin) from the venom of king cobra (Ophiophagus hannah).

The pharmacological effects of a purified neurotoxin from king cobra (Ophiophagus hannah) venom were studied. Using the hot-plate test, it is shown that this neurotoxin increased latency time dose-dependently when administered i.p. Similar analgesic action was observed when it was administered p.o. or i.c.v. The rota-rod performance, which is a good index for neurological deficits including sedation, muscle relaxant and impairment of motor activity and coordination, was not significantly affected in the dose range of 16-32 ng/g that caused analgesia. The toxin did not increase the convulsion threshold in the dose range of 8-64 ng/g in the maximal electroshock seizure tests. These results demonstrated that this neurotoxin produced analgesia in the dose range of 16-32 ng/g (i.p.) without causing any neurological or muscular deficits. It is further shown that such analgesic action was blocked by naloxone and L-NG-nitro-arginine methyl ester, suggesting the possible involvement of the opioid and nitric oxide systems, respectively. In view of the source of this neurotoxin (O. hannah) and its potent analgesic action, it is proposed that this toxin be named hannalgesin.

Analgesics↗
PubMed1995

L-arginine-nitric oxide pathway involvement in the nerve-evoked relaxant responses of the 5-HT precontracted chick isolated upper oesophagus.

1. The effects of tetrodotoxin (TTx) and the selective nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) on relaxant responses of the 5-HT precontracted chick isolated upper oesophagus to electrical field stimulation (EFS: 25-30V, 5 Hz for 10 s, 1 ms pulse width every 100 s) were investigated; the oesophagus was mounted under 1 g tension in Krebs solution containing 1 microM atropine. Appropriate tissue sections (30 microM thickness) of the chick oesophagus were also processed for NADPH-diaphorase histochemistry. 2. TTx (2 microM) and L-NAME (100-200 microM) inhibited the relaxant responses of the 5-HT precontracted chick oesophagus to EFS in a concentration-dependent manner; L-arginine (0.5-1 mM), but not D-arginine (0.5-1 mM), reversed the inhibition by L-NAME. In the absence of atropine and muscle tone, EFS produced contractile responses of the chick oesophagus that were completely abolished by 1 microM atropine, which also blocked the contractile response to acetylcholine (50 microM). 3. Under light microscopy, NADPH-diaphorase histochemistry confirmed the presence of nitric oxide synthase (NOS)-containing neurones and nerve fibres in the chick oesophagus. 4. The relaxant responses of the 5-HT precontracted chick isolated upper oesophagus to EFS are, therefore, mediated via the stimulation of non-adrenergic non-cholinergic nerves. These are likely to correspond to the histochemically identified NOS-containing neurones involved, presumably, in the synthesis and release of nitric oxide as the relaxant (inhibitory) neurotransmitter in this avian smooth muscle.

Animals↗
PubMed1995

Delivering health information databases on World Wide Web at the National University of Singapore.

The National University of Singapore (NUS) is one of the first medical schools in Asia to exploit the use of the World Wide Web on the Internet for the delivery of health information databases. Its WWW server was established in 1993 by the NUS Biocomputing Research and User Support (BRUS) technology group in collaboration with the Computer Resource Planning committee of the Faculty of Medicine. As a result of the early recognition of the powerful platform on which health information services can be delivered worldwide, the NUS effort has been accredited with a number of Internet firsts in the area of health informatics. The following are some of the NUS achievements: NUS-NCI CancerNet on the Web. The NUS developed and implemented the first WWW version of the popular CancerNet database offered by the National Cancer Institute, NIH, USA. Health Info-Com Network Medical Newsletter. The NUS developed and implemented the first WWW version of the medical newsletter, MEDNEWS which is edited by Dr. David Dodell, USA. It is now mirrored by the University of Pennsylvania in the United States and De Montfort University, U.K. Poisons Information Database. This first WWW implementation of a database on known plant, snake and other animal toxins with directories of antivenoms, toxinologists and poisons control centers around the world is offered by the NUS Venom and Toxin Research Group. HistoNet. This is a large collection of histology specimens from the NUS Department of Anatomy. MEDISTAT. This is the first WWW implementation of a Health and Population Statistical Database which contains information for Singapore, selected Asian countries and aggregate data for world regions. The Singapore Biotechnology Database. This database features companies and organizations involved in biotechnology and related activities in Singapore. Efforts are continuing to offer more value-added health information databases on the NUS WWW server and to link the server with other top-class information centers worldwide. Our mission is to identify the National University of Singapore as a global health information hub on the Internet.

Computer Communication Networks↗
PubMed1994

Pharmacological effects and pathological changes induced by the venom of Pseudechis australis in isolated skeletal muscle preparations.

The venom from the Australian king brown snake Pseudechis australis produced a concentration-dependent and progressive inhibition of directly and indirectly evoked twitches of the mouse hemidiaphragm: 2, 5 and 10 micrograms/ml of venom produced complete blockade of directly evoked twitches after 87 +/- 26 min, 66 +/- 28 min and 56 +/- 13 min, respectively, whereas twitches elicited by indirect stimulation were blocked after 43 +/- 4 min, 34 +/- 2 min and 21 +/- 2 min, respectively. Two, 5 and 10 micrograms/ml of the venom also progressively inhibited the twitch responses of the chick biventer cervicis muscle evoked by nerve stimulation: the time (min) to 90% blockade of the twitches were 127 +/- 12, 41 +/- 8 and 26 +/- 6, respectively. Light and electron microscopic studies confirmed that the venom caused severe muscle damage and necrosis in the chick and mouse skeletal muscle. The degree of muscle damage was proportional to the concentration of venom used. The muscle degeneration was characterized by disorganized myofibrils, dilatation of the sarcoplasmic reticulum and swollen or broken-down mitochondria. Depletion and a decrease in population of storage vesicles in the neuromuscular junction were also observed. Thus, the inhibition of neuromuscular function by the venom of P. australis was a consequence of the extensive morphological damage to muscle fibres, motor nerve terminals and cytoplasmic organelles which could be attributed to a direct myotoxic action presumably mediated by the enzymatic action of phospholipase A2 present in the venom of P. australis.

Animals↗
PubMed1994

Prejunctional action of the venom from the Indian red scorpion Mesobuthus tamulus on adrenergic transmission in vitro.

Venom (RSV) from the Indian red scorpion, Mesobuthus tamulus (Buthus tamulus), can cause increased peripheral sympathetic activity with consequent enhancement of adrenergic responses. We have therefore investigated the effects of RSV on adrenergic transmission in the rat isolated anococcygeus muscle. The effects of phentolamine (5 microM), tetrodotoxin (2 microM), guanethidine (5 microM), desipramine (1 microM) and reserpine pretreatment in vivo (5 mg/kg s.c. x 24 hr and 5 mg/kg i.p. x 3 hr) on the contractile responses of the rat anococcygeus muscle to RSV (1.5 microgram/ml), field stimulation, noradrenaline (NA, 1 microM or 3 microM) and tyramine (15 microM) were compared. The contractile responses to RSV and to field stimulation were completely blocked by phentolamine, tetrodotoxin, guanethidine and reserpine pretreatment, but the responses were potentiated by desipramine. The contractile responses to tyramine were completely blocked by phentolamine, reserpine pretreatment as well as desipramine. The responses to NA were completely blocked by phentolamine, but were potentiated by guanethidine, desipramine and reserpine. Relatively low concentrations (0.1 microgram/ml x 4) of RSV which did not produce any observable increase in tone of the anococcygeus muscle, potentiated the contractile response of the anococcygeus muscle to field stimulation, but not the responses to exogenous NA; 4-aminopyridine (25 microM x 2) also potentiated the muscle responses to field stimulation. HPLC measurements revealed only very low concentrations (0.10 +/- 0.03 mumol/g venom) of NA in RSV. Thus, the adrenergic agonist action of RSV in the rat isolated anococcygeus muscle can be attributed to the involvement of some prejunctional mechanism(s) of action that stimulates the release of neurotransmitter which differs from the indirect action mediated by tyramine.

Animals↗
PubMed1994

Stonustoxin: effects on neuromuscular function in vitro and in vivo.

Stonustoxin (8-50 micrograms/ml) produced a rapid and concentration-dependent rise in tension (contracture) of the electrically stimulated mouse hemidiaphragm followed by a gradual waning of tension from the peak to the baseline; the nerve-evoked and the directly (muscle)-evoked twitches of the hemidiaphragm were also progressively and irreversibly blocked in a time- and concentration-dependent manner. Stonustoxin (22 and 44 micrograms/ml) produced a similar rapid rise in tension of the chick biventer cervicis muscle as well as irreversible and concentration-dependent blockade of nerve-evoked twitches and contractures produced by acetylcholine (200 microM), carbachol (8 microM) and KCl (40 mM). The muscle contracture produced by stonustoxin was blocked by dantrolene sodium (6 microM) but not by tubocurarine (15 microM). Moreover, stonustoxin (40 micrograms/ml) did not inhibit nerve conduction in the toad sciatic nerve and stonustoxin (60 micrograms/ml) did not exhibit any anticholinesterase activity. The inhibition of neuromuscular function by stonustoxin in the mouse hemidiaphragm and chick biventer cervicis muscle can therefore be attributed to some irreversible myotoxic action(s) of the toxin, whereas the stonustoxin-induced muscle contractures could have been mediated via depolarization of muscle fibres.

Animals↗
PubMed1994

Action of Calloselasma rhodostoma (Malayan pit viper) venom on human blood coagulation and fibrinolysis using computerized thromboelastography (CTEG).

The effects of Malayan pit viper (Calloselasma rhodostoma) venom on human blood coagulation and fibrinolysis were studied in vitro using computerized thromboelastography. At low concentrations the venom had a coagulant effect shown by faster onset of the coagulation process (shortened SP and R), faster progress of the clot (increased angle and shortened K), and increased coagulation (TEG) index. The maximum amplitude (MA) was not affected, suggesting that the venom had no apparent effect on platelet function; and clot lysis was similar to that in the controls, suggesting that there was no primary fibrinolytic activity. At higher concentrations the venom had anticoagulant effects, SP and R were progressively shortened, but there was poor/no progress in the clot formed, evident from prolonged or absent K, diminished MA and reduced angle. These results show that C. rhodostoma venom has both coagulant and anticoagulant actions. The coagulant action may be due to Factor X activator predominance at low concentrations, while the anticoagulant action could be due to ancrod action. TEG is able to demonstrate the dual effect of this venom, previously described as a paradox, and may be a useful tool in the diagnosis and monitoring of envenomation patients.

Anticoagulants↗
PubMed1994

A review of stonefish venoms and toxins.

Venoms from stonefish (genus Synanceja) have marked effects on the cardiovascular and neuromuscular systems and on vascular permeability; the venoms also exhibit haemolytic and hyaluronidase activity. Recently, a toxic protein, stonustoxin (SNTX), was purified from the venom of S. horrida: the primary lethal action of SNTX has been attributed to its potent endothelium-dependent vasorelaxant activity causing a rapid, marked and irreversible hypotension; the other actions of SNTX resemble those of the stonefish crude venoms.

Amino Acid Sequence↗
PubMed1993

Stonustoxin: a highly potent endothelium-dependent vasorelaxant in the rat.

Stonefish venom has been documented to cause marked hypotension and respiratory difficulties in envenomed animals. Stonustoxin, a lethal protein recently isolated from the venom of the stonefish Synanceja horrida produced hypotension and, at concentrations above 20 micrograms/kg, death in anaesthetized rats, with no observable effects on nerve-evoked twitches of the tibialis and diaphragm muscles. Stonustoxin (20-160 ng/ml) induced endothelium-dependent relaxations of rat thoracic aortae precontracted with noradrenaline. Higher concentrations induced relaxations followed by contractions. Methylene blue, haemoglobin and the specific NO-synthase inhibitor L-NG-nitro arginine methyl ester inhibited stonustoxin-induced relaxations, while the cyclooxygenase inhibitor indomethacin was without effect. The results of the present study show that stonustoxin causes marked vasorelaxation of the rat isolated aorta, which appears to be due to the release of endothelium-derived relaxing factor (probably nitric oxide or nitric oxide-yielding substances) from the vascular endothelium, and this may be responsible for the in vivo hypotensive and lethal actions of stonustoxin and of stonefish venom.

Animals↗
PubMed1993

The structure of the venom gland of stonefish Synanceja horrida.

The structure of the venom gland of stonefish Synanceja horrida was studied using light microscopy, and transmission and scanning electron microscopy. The glands were covered with a fibrous capsule which divided the glandular tissue into many septa which carried numerous nerves and blood vessels. Transmission electron microscopy showed Type I cells with electron-dense material and tubular cisterns, Type II cells with dilated cisterns, sarcoplasmic reticulum and dense secretory granules. The secretory granules were globular and seen in monomer or polymer form. The secretory cells appear to be unique in comparison with the venom gland cells of snakes, scorpions or spiders.

Animals↗
PubMed1993

Purification and partial characterization of two cytolysins from a tropical sea anemone, Heteractis magnifica.

Two cytolysins, designated as magnificalysins I and II, were purified from a tropical sea anemone, Heteractis magnifica (formerly Radianthus ritteri). The purification steps involved Sephadex G-50 and CM-Sepharose chromatography followed by Mono S and Phenyl-Superose Fast Protein Liquid Chromatography. The relative mol. wt of magnificalysins I and II, determined by SDS-PAGE, was approximately 19,000, while their isoelectric points, determined by isoelectric focusing in immobilized pH gradients, were 9.4 and 10.0, respectively. Those toxins were found to have haemolytic and lethal activities. The haemolytic activities of magnificalysins I and II were 3.6 x 10(4) HU/mg and 3.3 x 10(4) HU/mg, while their LD50 (i.v., mice) values were approximately 0.14 microgram/g and 0.32 microgram/g, respectively. The amino acid composition and N-terminal sequences of magnificalysins I and II were also obtained. They do not possess any cysteine or cystine residue, but are rich in basic and hydrophobic amino acids. The N-terminal amino acid sequences of magnificalysins I and II are ALAGTIIAGASLTFKILDEV and SAALAGTIIDGASLGFDILNKV, respectively. These are highly homologous to cytolysins from other sea anemones, particularly cytolysin III from Stichodactyla helianthus, a Caribbean anemone.

Amino Acid Sequence↗
PubMed1993

Molecular cloning of a cardiotoxin structural gene from Malayan spitting cobra (Naja naja sputatrix).

The structural gene and cDNA encoding cardiotoxin in Naja naja sputatrix have been cloned and characterized with a view to study the gene protein relationships and also to produce pure protein in large amounts. Using the polymerase chain reaction on the total RNA isolated from the venom glands, the structural gene (180 bp) has been synthesized and expressed in Escherichia coli to produce a fusion protein with beta-galactosidase. Immunoblotting using polyclonal antibodies raised against the total venom in rabbits demonstrated the presence of cross-reacting proteins in plaques produced by recombinant lambda gt11 phages.

Amino Acid Sequence↗
PubMed1993

The black scorpion Heterometrus longimanus: pharmacological and biochemical investigation of the venom.

Documentation on the biological activity (including the lethality) of the venom (BSV) from the black scorpion Heterometrus longimanus is lacking. We have investigated the effects of BSV on adrenergic transmission using the rat isolated anococcygeus muscle (Acm), since the venom from several species of scorpions causes peripheral sympathetic nerve stimulation with enhanced adrenergic responses. The catecholamine content in BSV was also measured by HPLC. The effects of phentolamine (5 microM), guanethidine (5 microM), desipramine (1.5 microM), tetrodotoxin (2 microM) and reserpine pretreatment in vivo (5 mg/kg s.c. x 24 hr and 5 mg/kg i.p. x 3 hr) on contractile responses of the rat Acm to field stimulation, crude BSV (2-10 microliters in 6 ml bath), noradrenaline (3 microM), tyramine (10-15 microM), carbachol (2-3 microM) and potassium chloride (50-75 mM) were investigated. BSV mimicked the agonist actions of noradrenaline (NA) by acting directly on postjunctional alpha-adrenoceptors in the anococcygeus muscle. The LD50 of crude BSV injected i.v. into mice was 0.13 ml per kg mouse. Sequential ultrafiltration of the crude BSV revealed the presence of a substance of low mol. wt which mediates the postjunctional alpha-agonist actions of BSV. HPLC measurements confirmed the presence of noradrenaline (NA; mean concentration of 1.8 +/- 0.3 mM) in BSV; the dopamine concentration (mean of 31 +/- 4 microM) was 60-fold lower than that of NA, whereas adrenaline was not detected in all the 15 samples investigated. Thus, the presence of NA in BSV can account for the postjunctional alpha-agonist actions of the venom in the Acm.

Animals↗
PubMed1992

The effects of Indian red scorpion Buthus tamulus venom in vivo and in vitro.

The Indian red scorpion Buthus tamulus (or Mesobuthus tamulus) can cause fatal envenoming, but its mechanism of action is unclear. Venom was tested in vivo in anaesthetized rats and in vitro on isolated cardiac and skeletal muscle preparations. In vivo, the venom caused marked rhythmical fluctuations in blood pressure preceding cardiovascular collapse and death. On sheep Purkinje fibres, venom could induce spontaneous action potentials and cause prolongation of action potential duration. In chick biventer cervicis and mouse triangularis sterni preparations, venom enhanced the release of acetylcholine and induced repetitive firing of nerve action potentials in response to single shock stimulation. High concentrations caused stimulation then block of neuromuscular transmission. The main effects of Buthus tamulus venom are likely to be due to toxins that affect the opening of Na+ channels in nerves and muscles. This will cause an increase in the release of neurotransmitters in the peripheral nervous system, which may produce cardiovascular abnormalities and respiratory paralysis.

Action Potentials↗
PubMed1991

A Blastocystis species from the sea-snake, Lapemis hardwickii (Serpentes: Hydrophiidae).

Observations were made on Blastocystis isolated from the sea-snake, Lapemis hardwickii. Exponential growth of the organism was observed between 2 and 4 days of culture. Vacuolated, amoeboid and granular forms were observed in cultures, similar to B. hominis. The optimal growth temperature for the sea-snake Blastocystis was 24 degrees C compared with 37 degrees C for B. hominis. The karyotypic patterns of B. hominis and the sea-snake Blastocystis were studied in the clamped homogeneous electric field (CHEF) technique and found to be different. Based on the above differences, the sea-snake Blastocystis was designated as Blastocystis lapemi sp. nov.

Animals↗