The author provides an account of the discovery of a previously undescribed disease of horses and a description of the studies involved in determining the aetiology of the disease. The causative virus, now named Hendra virus (HeV), is the reference virus for a proposed new genus within the virus family Paramyxoviridae. The virus is a lethal zoonotic agent able to cause natural disease in humans and horses and experimentally induced disease in cats, guinea-pigs and mice. The virus also naturally infects species of the family Megachiroptera, mainly subclinically, and such animals are the natural host of HeV. The virus appears to transmit readily between species of Megachiroptera, but not readily between horses under natural and experimental conditions, or from horses to humans. The method of transmission from bats to horses is not known. Three incidents of HeV disease in horses have been recorded in Australia--two in 1994 which caused the death of two humans and fifteen horses and one in 1999 which involved the death of a single horse. Hendra virus is related to Nipah virus, the virus that caused disease and mortality in humans, pigs, dogs and cats in Malaysia during 1998 and 1999.
The immunomodulatory effects of morphine and the active components of marijuana, particularly tetrahydrocannabinol, on various aspects of the host immune parameters include alterations in humoral, cell-mediated and innate immunity. Most studies have shown immunosuppressive effects due to use of these abused substances, although there are reports that they may not produce any deleterious effect and may even enhance some aspects of host immunity. They reduce resistance to cancer growth and microbial pathogens in animals.
The immunological characteristics of 26 strains of Japanese encephalitis virus (JEV) isolated in Japan and Malaya between 1935 and 1966 have been investigated mainly by the antibody-absorption variant of the haemagglutination-inhibition test, and to a certain extent also by conventional haemagglutination-inhibition and complement-fixation tests. The antibody-absorption technique shows promise as a routine method for the immunotyping of JEV.At present, two immunotypes can be distinguished. One comprises 2 strains, Nakayama-NIH and I-58, and is designated as the I-58 immunotype. The other immunotype, JaGAr 01, comprises 17 strains which share the characteristics of the JaGAr 01 strain, including one subline of the Nakayama strain, Nakayama-Yakken. The Nakayama-RFVL strain was found to have the characteristics of both immunotypes. The I-58 immunotype differs more markedly from related arboviruses, such as the Murray Valley encephalitis virus and the West Nile Eg101 strain, than does the JaGAr 01 immunotype.Evidence is presented which suggests that a given JEV strain can change immunotype on repeated passage through mice.
The present investigation was aimed at determining the effects of hexane, acetone, methanol and aqueous extracts of Acorus calamus leaves (ACHE, ACAE, ACME and ACAQE) on cholinergic and histaminic system using isolated frog rectus abdominis muscle and guinea pig ileum. A dose dependent potentiation of Ach response (anticholinesterase like effect) was found with ACAE and ACME at 0.25, 0.5, 0.75 and 1 mg/ml, but at higher dose of ACAE, ACME, ACAQE and ACHE (5, 20 mg/ml) inhibit the Ach response (antinicotinic effect). These results revealed biphasic effect of Acorus calamus leaves extracts on acetylcholine induced contractile response in isolated frog rectus abdominis muscle preparation (i.e. potentiation effect at lower dose and inhibitory effect at higher dose). Studies on isolated guinea pig ileum demonstrated antihistaminic effect in a dose dependent manner (100-1000 µg/ml) with ACAE, ACME and ACAQE. In addition, the dose dependent inhibition of Ach response (antimuscarinic effect) was observed with ACAE and ACME. In conclusion, Acorus calamus leaves extracts exerts antinicotinic, anticholinesterase like activities in isolated frog rectus abdominis muscle and antihistaminic, antimuscarinic effect in guinea pig ileum. It has been suggested that these observed activities can be further studied for therapeutic potential of Acorus calamus leaves in the treatment of cognitive disorders and asthma.
This study aimed to elucidate the mechanism(s) of the spasmogenic action of Loranthus ferrugineus in isolated guinea pig ileum. Thus the contractile responses of guinea pig ileum to graded additions of either L. ferrugineus methanol extract or its n-butanol fraction were tested in the presence and absence of various pharmacological interventions. The data showed that L. ferrugineus methanol extract and the n-butanol fraction produced a concentration-dependent spasmogenic effect in isolated guinea pig ileum segments. These effects were significantly inhibited in the presence of 1 microM atropine. In contrast, the response to the lowest concentrations of L. ferrugineus methanol extract (0.25, 0.5 and 1 mg/mL) and n-butanol fraction of L. ferrugineus (0.125, 0.25 and 0.5 mg/mL) were considerably enhanced in the presence of 0.05 microM neostigmine. Neither L. ferrugineus methanol extract nor n-butanol fraction contractile responses were affected upon the incubation of the ileal segments with 100 microM hexamethonium. The results of this study show that the spasmogenic effect of L. ferrugineus is possibly mediated through a direct action on intestinal muscarinic receptors. It is suggested that the bioactive constituents of L. ferrugineus serve as a substrate for acetylcholinesterase.
1. In vitro studies of non-specific histidine decarboxylase activity was low or absent in control guinea-pigs and unchanged 9 or 27 hr after chlorpromazine (CPZ) injection intraperitoneally. 2. However, specific histidine decarboxylase activity was found in the control tissues and was increased 9 hr but not 27 hr after CPZ injection.
We have investigated the effect of indomethacin on histamine- and acetylcholine (ACh)-induced responses in the intact and denuded epithelium of guinea pig isolated tracheal smooth muscle. Epithelium removal resulted in increased responsiveness to ACh and histamine. Indomethacin (2.8 microM) enhanced the sensitivity of both intact and denuded preparations to histamine and ACh. These findings suggest that the tracheal epithelium of guinea pig plays a protective role against bronchoconstrictors, such as ACh and histamine. Furthermore, indomethacin-mediated hyperresponsiveness caused by these agonists in epithelium denuded preparations might be a reflection of removal of prostaglandin (PG) biosynthesis. A similar process of interaction in indomethacin-treated asthmatic patients (with damaged airway epithelium) might take place. The significance of these findings is discussed.
The effect of the total glysosidic extract of the plant Sarcolobus globosus was investigated on the contractions of the smooth muscle of the guinea-pig ileal longitudinal muscle and taenia coli. In the ileal longitudinal muscle, addition of the extract inhibited the electrical field-stimulated twitches. Similarly to verapamil, it also reduced the contractions of the muscle to acetylcholine, histamine and KCl. However, only the tonic contraction to KCl was reversed by increasing the extracellular calcium concentration. In the taenia coli, lower concentrations of both the extract and verapamil induced a parallel displacement of the dose-response curves to calcium (0.30-30 mM). Addition of the extract also dose-dependently inhibited the KCl-induced contraction of the taenia coli. Increasing the calcium concentration increased the IC50 values of the extract. The result suggests that the inhibitory effect of the Sarcolobus globosus extract on the smooth muscle, like verapamil, is mainly due to inhibition of calcium influx.
The electrically stimulated guinea-pig ileum and spontaneously contracting guinea-pig ileum preparations were employed in studies on the effects of an alcoholic extract and two flavonoid compounds, quercetin and quercetin-3-arabinoside, extracted from the leaves of Psidium guajava. The extract showed a morphine-like inhibition of acetylcholine release in the coaxially stimulated ileum, together with an initial increase in muscular tone, followed by a gradual decrease. The morphine-like inhibition was found to be due to quercetin, starting at concentrations of 1.6 micrograms/ml. The glycoside did not show any such action at concentrations of up to 1.28 mg/ml. The extract inhibited spontaneous contractions in the unstimulated ileum with a concentration-response relationship.
Selected indole-based kratom alkaloids were evaluated for their opioid and adrenergic receptor binding and functional effects, in vivo antinociceptive effects, plasma protein binding, and metabolic stability. Mitragynine, the major alkaloid in Mitragyna speciosa (kratom), had higher affinity at opioid receptors than at adrenergic receptors while the vice versa was observed for corynantheidine. The observed polypharmacology of kratom alkaloids may support its utilization to treat opioid use disorder and withdrawal.
Isolation of rickettsiae from patients' blood samples and organ samples of wild rodents from areas with high seroprevalence of rickettsial infections was attempted using cell culture assay and animal passages. L929 mouse fibroblast cells grown in 24 well tissue culture plate were inoculated with buffy coat of febrile patients and examined for the growth of rickettsiae by Giemsa, Gimenez staining and direct immunofluorescence assay. No rickettsiae were isolated from 48 patients' blood samples. No symptomatic infections were noted in mice or guinea pigs infected with 50 organ samples of wild rodents. There was no rickettsial DNA amplified from these samples using various PCR detection systems for Orientia tsutsugamushi, typhus and spotted fever group rickettsiae.
1. The major phospholipase A2 (PLA-DE4) of the venom of Trimeresurus purpureomaculatus (shore pit viper) has been purified to electrophoretic homogeneity. 2. The isoelectric point of the purified enzyme was determined to be 4.20, and the mol. wt was 31,700 as estimated by Sephadex G-75 gel filtration chromatography; and 14,000 as estimated by SDS-polyacrylamide gel electrophoresis. The purified enzyme hydrolyzed phosphatidylcholine (PC) faster than phosphatidylethanolamine (PE), whereas phosphatidylserine (PS) was not hydrolyzed at all (PC greater than PE greater than PS =0). However, in reaction system consisted of mixtures of PC and PS, phosphatidylserine was effectively hydrolyzed by the enzyme. 4. The phospholipase A2 exhibited edema-forming activity but not hemolytic, hemorrhagic or anticoagulant activities. It was not lethal to mice at a dosage of 10 micrograms/g by i.v. route.
The coding region of guinea pig peroxisome proliferator activated receptor gamma1 (gpPPARgamma1) cDNA was successfully cloned from adipose tissue by reverse transcription polymerase chain reaction (RT-PCR) using the designated primers based on the conserved regions of the other mammalian PPARgamma1 sequence. From RT-PCR, a combination of three cDNA fragments that comprised of the full length coding region PPARgamma1 cDNA gene were amplified, with the size of 498, 550 and 557 bp, respectively. All three fragments were then successfully assembled by utilising the internal restriction sites present at the overlapping regions to give rise to the full-length coding region of gpPPARgamma1 with the size of 1428 bp and consisting of 475 amino acids. Guinea pig PPARgamma1 is highly conserved with those of other species at protein and nucleotide levels. Gene expression studies showed that gpPPARgamma mRNA was predominantly expressed in adipose tissue followed by lung and spleen. However, at the protein level, PPARgamma was also found to be expressed in skeletal muscle.
1 Candoxin (MW 7334.6), a novel toxin isolated from the venom of the Malayan krait Bungarus candidus, belongs to the poorly characterized subfamily of nonconventional three-finger toxins present in Elapid venoms. The current study details the pharmacological effects of candoxin at the neuromuscular junction. 2 Candoxin produces a novel pattern of neuromuscular blockade in isolated nerve-muscle preparations and the tibialis anterior muscle of anaesthetized rats. In contrast to the virtually irreversible postsynaptic neuromuscular blockade produced by curaremimetic alpha-neurotoxins, the neuromuscular blockade produced by candoxin was rapidly and completely reversed by washing or by the addition of the anticholinesterase neostigmine. 3 Candoxin also produced significant train-of-four fade during the onset of and recovery from neuromuscular blockade, both, in vitro and in vivo. The fade phenomenon has been attributed to a blockade of putative presynaptic nicotinic acetylcholine receptors (nAChRs) that mediate a positive feedback mechanism and maintain adequate transmitter release during rapid repetitive stimulation. In this respect, candoxin closely resembles the neuromuscular blocking effects of d-tubocurarine, and differs markedly from curaremimetic alpha-neurotoxins that produce little or no fade. 4 Electrophysiological experiments confirmed that candoxin produced a readily reversible blockade (IC(50) approximately 10 nM) of oocyte-expressed muscle (alphabetagammadelta) nAChRs. Like alpha-conotoxin MI, well known for its preferential binding to the alpha/delta interface of the muscle (alphabetagammadelta) nAChR, candoxin also demonstrated a biphasic concentration-response inhibition curve with a high- (IC(50) approximately 2.2 nM) and a low- (IC(50) approximately 98 nM) affinity component, suggesting that it may exhibit differential affinities for the two binding sites on the muscle (alphabetagammadelta) receptor. In contrast, curaremimetic alpha-neurotoxins have been reported to antagonize both binding sites with equal affinity.
A 22-year-old Malay female presented with left eye floaters for 2 weeks, associated with temporal visual field defect and metamorphopsia for 3 days. She has a guinea pig and a hedgehog at home, but denied being bitten or scratched by them. Her visual acuity at presentation was 6/12 on the left eye and 6/6 on the right eye. Her left eye relative afferent pupillary defect was barely positive with mild anterior chamber reaction. Fundus examination of the left eye showed mild vitritis, swollen optic disc with macular star, crops of active choroidal lesions at superonasal retina with a linear arrangement in the form of migratory track nasally. However, there were no nematodes seen on fundus examination. Investigations showed normal full blood count with no eosinophilia and positive serology test for Bartonella henselae. She was diagnosed to have dual infection - diffuse unilateral subacute neuroretinitis (DUSN), based on the presence of crops of choroidal lesions with migratory track, and cat scratch disease (CSD) based on a positive serological test. She was treated with oral albendazole 400 mg 12 hourly for 6 weeks for DUSN and oral doxycycline 100 mg 12 hourly for 4 weeks for CSD. Focal laser had been applied to the area of migratory track in the left eye. Her left eye vision improved to 6/6 at 1 month after treatment, with resolution of neuroretinitis.