Leptospiral carriage by Mice and Mongooses on the island of Barbados

Leptospirosis is a zoonotic disease, maintained by chronic infection of the kidneys of reservoir animals, usually small mammals. Infection in humans is acquired from direct or indirect exposure to the urine of infected animals. Leptospirosis has a high incidence in tropical regions, and has been studied extensively in several Caribbean countries. We studied the carriage of Leptospira serovars by two small mammals which are potential maintenance host of the disease in Barbados. A total of 136 mongooses (Herpestes auropunctatus) and 97 mice (Mus musculus) were caught in live traps. Leptospiral antibodies were detected by microscopic aggutination test (MAT) using antigens representing 12 serogrouops, and kidney tissues were inoculated into polysorbate medium for isolation of leptospires. The seroprevalence (at a titre of o 100) in mice was 28.2 percent (24/85, 95 percent CI 19.0, 39.1) and in mongooses 40.7 percent (48/118, 95 percent CI 20.1, 39.0) and from 4 mongooses ( 2.9 percent, 95 percent, CI 0.8, 7.4). Mouse isolates were identified as serovars arborea (17) and bim (7). As in other parts of the world, common house mice (Mus musculus) represent a significant reservoir of leptospirosis. Although carriage of the Ballum serovar, arborea, was not unexpected, this represents the first time that an animal reservoir of serovar bim has been identified. This is significant because bim causes about 63 percent of human leptospirosis in Barbados, and control efforts and education for prevention can now be targeted at a specific reservoir. (AU)

Congenital afibrinogenemia: mutations leading to premature termination codons in fibrinogen AO-chain gene are not associated with the decay of the mutant mRNAs

Congenital afibrinogenemia is a rare coagulation disorder with autosomal recessive inheritance, characterized by the complete absence or extremely reduced levels of fibrinogen in patients, plasma and platlets. Eight afibrinogemic probands, with very low plasma levels of immunoreactive fibriogen were studied. Sequencing of the fibrinogen gene cluster of each proband disclosed 4 novel point mutations (1914C>G, 1193G> T, 1215delT, and 3075C> T) and 1 already reported (3192C>T). All mutations, localized within the first 4 exons of the AO-chain gene, were null mutations predicted to produce severely truncated AO-chains because of the presence of premature termination codons. Since premature termination codons are frequently known to affect the metabolism of the corresponding messenger RNAs (mRNAs), the degree of stability of each mutant mRNA was investigated. Contransfection experiments with plasmids expressing the wild type and each of the mutant AO-chains, followed by RNA extraction and semiquantative reversetranscriptase-polymerase chain reaction analysis, demonstrated that all the identified null mutations escaped nonsense-mediated mRNA decay. Moreover, ex vivo analysis at the protein level demonstrated that the presence of each mutation was sufficient to abolish fibrinogen sectretion. (AU)

The parasite fauna of two populations of feral pigeons from North and South Trinidad [abstract]

Two populations of feral pigeons (Columba livia) from two locations in Trinidad were examined for their internal and external parasites. Twenty-five birds were live-captured from the Eric Williams Medical Sciences Complex (EWMSC) while twenty were captured in San Fernando. Microscopic examination of blood smears for haemoparasites revealed that both populations had high infection rates of Plasmodium and Haemoproteus and relatively low infection rates of Toxoplasma. Examination of faecal samples revealed that a high proportion of birds were infected with with coccidia, reaching 100 percent in birds from the EWMSC. Other gastrointestinal parasites observed included Capillaria, Ascardia and termatodes. All birds from both localities had high burdens of lice, mite and pigeon fly infestations. The significnce of these results in relation to the role of wild pigeons as reservoirs of pathogens affecting the poultry industry and in the transmission of zoonotic diseases is discussed. (AU)

A preliminary investigation on the use of imidocarb dipropionate in the prophylaxis of anaplasmosis and babesiosis [abstract]

The prophylactic effect of imidocarb dipropionate on anaplasmosis and babesiosis was studied using twenty-seven heifers at the university field station. Fifteen animals were administered imidocarb dipropionate intramuscularly at a dose of 2mg-kg 1 while twelve were left as controls. All animals were subsequently turned out to pasture from a feedlot environment which was tick-free. Over a period of seven months, the heifers were monitored for tick infestation, weight gain, body temperature, haematological para-meters such as packed cell volume, haemoglobin, white blood cell count, total plasma protein, the differences in other parameters between treated and untreated control heifers were not significantly different. It is concluded that the administration of imidocarb dipropionate for the purpose of prophylaxis of babesiosis and/or anaplasmosis in this situation was of no significant value. (AU)

Effect of water extract of Coraili (Momordica charantia) on blood glucose levels in Sprague Dawley Rays [abstract]

Water extracts from the fruit of the coraili plant, Mormordica charantia, have been reported to have hypoglycaemic effect. The fruit of this plant is eaten as a vegetable by man. Significant lowering of blood glucose levels has been observed following the oral administration of coraili fruit extracts. However, some authors have shown that there are no beneficial hypoglycaemic effect from fruit extracts. In this experiment, water extract of the entire coraili fruit was administered orally to alloxan-diabetic Sprague Dawley Rats ad libitum for 7 hours. The rats were placed on normal diet during the experiment. Results showed that 7 hours after the administration of this extract, blood glucose levels dropped significantly. It was also observed that, 7 hours after the discontinuation of the administration of the extract in alloxan-diabetic rats, blood glucose levels rose close to the pre-administration levels. The implications of these findings will be discussed. (AU)

A molecular form of memory protects the brain from the effects of acute hypoxia [abstract]

Long-term potentiation (LTP) is a molecular engram of memory. Previous work has demonstrated that LTP decreases the sensitivity of glutamate receptors in the rat hippocampus. Glutamate has beem implicated in the pathogenesis of hypoxic/ischaemic damage. We therefore tested the hypothesis that LTP could reduce the effects of LTP on hypoxia in the rat hippocampus. The effects of LTP on hypoxia were measured by the changes in the extracellular potentials recorded from the hippocampal slice. Hypoxia was induced by perfusing the slice with artificial cerebrospinal fluid that contained varying concentrations of oxygen. Each slice was initially exposed to the hypoxic medium for 1.5-3.0 minutes. This led to a decrease in the potentials, which recovered to control levels within 5 minutes. Repeat exposure to the same hypoxic medium for the same duration as the first, also caused a reduction in the potentials. There was no significant difference between the degree of reduction caused by the first or second exposure for all types of hypoxic media tested (p >0.05; paired t test). In some slices, LTP was induced after the first hypoxic exposure. LTP brought about an inhibition of the reduction in potentials caused by the second hypoxic insult; the differences in reducation in potentials were highly significant for all the hypoxic media used (p <0.01; paired t test). The neuroprotective effects of LTP were not prevented by cyclothiazide (an inhibitor of AMPA receptor desensitization) or NOS inhibitors (antagonists of intracellular nitric oxide production). These compounds have been shown to be effective in blocking the effects of LTP on the actions of exogenously applied AMPA and NMDA, respectively. The neuroprotective effects of LTP were similar to that of propentofylline, a known neuroprotective compound. We conclude that LTP causes an appreciable protection of the hippocampus slices to in-vitro models of acute hypoxia. There have been reports that there is a possible inverse relationship between educational attainment and the development of dementia and the results of our study may have a role to play in this relationship. (AU)

Demostration of collaterization of the abdominal vagus in the rat using the double flourescent dyes technique [abstract]

Since the earlier report of Mitchel (1935), the central origin of preganglionic parasympathetic fibres has been studied by various investigators using different techniques and animal species. While it is now generally accepted that the dorsal motor nucleus of the vagus nerve (DMNV) is the principal source of preganglionic parasympathetic fibres to several organs in the thorax and abdomen, there has been persistent controversy as regards topographic representation of these organs in the DMNV. In a previous study in the ferret using the Horseradish peroxidase technique, some degree of topographic representation of the subdiaphragmatic part of the gastrointestinal tract was observed. It was, however, noted that no part of this nucleus is exclusively responsible for innervation of any segment of the gut. The author went on to speculate that the pattern of representation of the gut demostrated in the study might supply more than one segment of the gut by collaterization. The present study was thus designed to test this hypothesis. A total of 16 male and female Sprague Dawley rats weight range from 350 to 500g were used for the study. Four of these rats were used as control while the remaining 12 were used as experimental rats. Eight rats were injected with 1æ1 of 5 percent Diamidino yellow (DY) by multiple penetrations into the walls of the stomach while the same quantity and percentage of Fast blue (FB) was injected in the same manner into the walls of the duodenum and upper jejunum in the eight rats. Two rats had multiple injections of 1æ1 of 5 percent DY into the walls of the stomach only and two other rats had multiple injections of 1æ1 of 5 percent FB into the walls of the duodenum and upper jejunum only. Four control rats were injected with 1æ1 of normal saline (2 in the stomach and 2 in the intestine) in the same manner in which the experimental rats were injected. Each rat was anaesthetized with pentobarbitone and then perfused transcardially 14 days after the injections. Serial sections of the medulla were cut at 20-micron thickness with the cryosat and the sections examined with a Nikon Apaphot flourescence microscope. The result of the experiment revealed that in 8 rats injected with DY and FB some cells of the DMNV were labelled with DY only, some with FB only and some were doubly labelled with FB and DY. The two rats injected with FB showed FB labelled cells only while the two injected with DY showed DY labelled cells only. (AU)

Food saftey: an examination of the potential impact on the economies of countries of the Caribbean Community [abstract]

Food safety pertains to the prevention, reduction or elimination of the risk of ill-health as a result of the consumption of foods whether fresh or processed, obtained through the domestic market or by international trade. Food saftey issues therefore impact on agricultural production and trade, as well as on the manufacture of processed foods and on the preparation and service of meals, whether these be in a hotel/restaurant environment or by itinerant street vendors. Agricultural production, trade and tourism are together significant contributors to the output of the open economies of the countries of the Caribbean Community. The discussion examines the findings of a recent assessment of the food safety status of Caribbean Community (CARICOM) Member States, which focussed on food safety in respect of plant, animal and human health systems in the various countries. The economic structure of selected countries is highlighted together with an indication of the trends in trade. The findings of the food safety assessment are then reviewed in the context of their possible impact on the economic output of the countries. The analysis showed that agricultural production and trade play a critical role in the economic output of many CARICOM States, Through their contribution to export earnings as well as employment. Tourism is also important in this regard. Inadequate attention to food safety issues can result in loss of market share either through a shift in purchasing patterns as experienced by other countries, or through detention by the regulatory agency of the importing country. Weak food safety policies could also jeopardize the tourism sector. Improvements in the food safety system and its infrastructure would serve to enhance the earning potential of the agricultural and tourism sectors and this should lead to greater economic output from those sectors. (AU)

Gestational stage sensitivity to ultrasound effect on postnatal growth and development of mouse [abstract]

Pregnant Swiss albino mice were exposed to diagnostic ultrasound (3.5 MHz, 65 m W, Isptp= 1 W/cm2, 1sata=240 W/ccm2) for 30 min on any one day from day 10 to 18 gestation. A sham exposed control group was maintained for comparison. A minimum of 15 pregnant mice were exposed in each group. Exposed as well as control animals were left to complete gestation and parturition. Then offspring were observed during early postnatal development for any changes in physiological reflexes like pina detachment, eye opening, fur development, postnatal mortality, body weight, body length, head length and head width up to 6 weeks of age. Ultrasound exposure at any of the gestational age did not have any effect on the timing of onset of the physiological reflexes. But there was a significant change in the postnatal mortality, body weight, body length after exposure to ultrasound on the 14th and 16th day post coitus. Head length and head width also significantly decreased in all the exposed groups when compared to the control. The present study demonstrates that ultrasound can induce harmful effects on mouse growth and development when given at certain critical periods of gestation. (AU)

Increased BAEP latency and reduced brain cytochrome c oxidase activity observed in the Suzuki model of Alzheimer's disease [abstract]

Cytochrome c oxidase (COX), the terminal respiratory enzyme, is reported to be deficient and to exhibit reduced activity in a number of neurodegenerative disorders. The Alzheimer's rabbit model is based on the intracerebral injection of Holt's adjuvant, an aluminum salt solution. This model was used to compare the brain activity and the activity of brain COX in treated and controlled rabbits. Of a total of 26 New Zealand white rabbits, thirteen were injected intracerebrally with Holt's adjuvant solution, five with physiologically saline solution and the remainder were kept as controls. The auditory responses (BAEP) of the rabbits were monitored for 14 days before injections and 14 days thereafter. The animals were then sacrificed and brain mitochondrial extracts were used for SDS-PAGE analysis, difference spectra spectrophotometry and polarographic assays. The results of SDS-PAGE showed that there were no differences in the protein composition of the brain mitochondria of the three groups. Similarly, difference spectra (reduced minus oxidized, 400-630 nm) from both treated groups were identical to that of the control with characteristic maxima centered around 434, 550 and 604 nm. Polarographic assays, however, showed that while the enzyme from both treated groups displayed the characteristic biphasic kinetics, there was reduced activity in the enzymes from the brain of rabbits receiving the adjuvant but not the saline solution. This result is significant in light of the fact that several researchers have reported reduced activity of COX from Alzheimer's disease (AD) patients. Of particular significance, BAEP results reveal an increase in the interpeak latency between peaks III and V of the Holt's injected but not the saline injected or control rabbits. This latter result suggests that monitoring the BAEP might provide a simple non-invasive method for confirming AD. (AU)

Activation of AMPA receptors in the cerebral cortex may be protective against migraine headache [abstract]

The pathogenesis of migraine involves a spreading depression of neurons in the cerebral cortex resulting from over-excitation by released neurotransmitters or electrolytes. Glutamic acid is the most common excitatory neurotransmitter in the brain and spinal cord of mammals. Analogues of glutamic acid including AMPA (DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-asparatic acid) act on different receptors to depolarize the neurons of the cerebral cortex. Previous work has shown that evoked electrical potentials recover from the effects of NMDA on this neuronal network, suggesting a form of neuronal desensitization or network adaption. We have extended these observations by examining the effects of AMPA in the cerebral cortex, the interactions between AMPA and NMDA and the interactions between AMPA and spreading depression. Male Sprague-Dawley rats were anaesthetized with urethane and potentials evoked at the cortical surface by electrical stimulation of the contralateral forepaw. The compounds were applied topically to the cortex by a cortical cup. NMDA at 0.05-0.25mM caused a concentration-dependent decrease in the amplitude of the potentials, with the highest concentration always abolishing them. AMPA at 0.05mM did not affect the evoked potentials when applied alone, but when 0.25mM NMDA was preceeded by an application of AMPA, the latter prevented the NMDA effects in a concentration-dependent manner. Such AMPA-NMDA interactions were inhibited by CNQX (6-cyano-7-nmitroquinoxalinne-2, 3-dione, an antagonist of AMPA) and ehanced by cyclothiadize (which prevents AMPA desensitization). Topical application of AMPA, (0.5mM) prevented the electrophysiological manifestation of spreading depression in the cerebral cortex. Chlormethiazole, a GABA-mimetic drug that is known to prevent epileptic seizures, at 0.2-2mM, was not effective in preventing the spreading depression. These results suggest that, in the rate cerebral cortex, activation of the AMPA receptor (a glutamic acid receptor subtype) can induce a loss of neuronal response to activation of another glumatic acid receptor subtype, the NMDA receptor. Also, activation of the AMPA receptor in the cerebral cortex seems to have a neuroprotective role against the spreading depression that has been implicated in migraine. (AU)

Pharmacological evaluation of some local plant extracts claimed to be used abortifacients in folklore practice

OBJECTIVE: Several local plant extracts are used in folklore practice as abortifacients. The objectives was to determine the scientific basis, if any, for these claims. METHODS: Aqeous extracts were prepared from 6 plants collected from St.Thomas, Jamaica: Leonotis nepetifolia (LN), Mentha pulegium (MP), Phyllanthus amarus (PA), Stachytarpheta jamaicensis (SJ), Gliricidia sepium (GS) and Wedelia gracilis (WG). The extracts were tested for contractile activity on isolated mouse uteri maintained in de Jalons solution. The effects of indomethacin and atropine on the contractions were used to indicate the possible mechanism of action. RESULTS: Three plant extracts (LN, MP and PA) produced dose-dependent contractions of the non-pregnant and pregnant mouse uteri. No contractions were observed with the other three extracts (SJ, GS, and WG). The contractions produced by MP were significantly reduced by indomethacin (p<0.05) but not by atropine. Contractions produced by LN and MP were blocked by either drug. Pregnant mice given LN litterd with live offspring within 24 hours. CONCLUSIONS: Of the 6 plants evaluated, 3 contracted the uterus in vitro but only one (LN) had a significant action in vivo. The contractile effect of MP may possibly be mediated via prostaglandins. However, this plant extract showed significant toxicity in vivo. (AU)

Stress, marijuana and addiction in an animal model [abstract]

OBJECTIVE: Acute stress has been shown in rats to increase self-administration for drugs such as cocaine, morphine and amphetamine. We aimed to explore this phenomenon for marijuana extract (ME) and its psychoactive component, 9-tetra-hydrocannabinol ( 9 THC). METHODS: Six female Sprague Dawley rats were followed free access to a black grid-floored chamber and a white one with a floor strewn with wood shavings. The time spent in each chamber indicated a preference for the black chamber. On alternate days of an 8-day conditioning period, six Sprague Dawley rats were first subjected to an acute stress for 10 minutes followed by an intraperitoneal administration of ME (saline vehicle) or 2m/kg 9 THC (oil vehicle). The doses used were those which had been previously shown to have neither aversive nor rewarding effects. The rats were then confined to the white chamber. On the other days, the rats were administered the respective vehicle and confined to the black chamber. After this conditioning period, the rats were once again allowed free access to the chambers and the pre-conditioning period times in each chamber were compared to the post-conditioning times. The stressors were: restraint stress (RS), swimming stress (SS) or acute isolation stress (ACI). RESULTS: When ME was administered with RS, the mean time spent in the drug+stress chamber increased compared with the pre-conditioning time with a significance level of p= 0.07. This result was repeated with 2 mg/kg of 9-tetrahydrocannabinol (p= 0.07). The ACI + ME combination resulted in an increase, which was significant (p< 0.05). CONCLUSIONS: Our results provide some evidence to support a possible influence of acute stress on reward to marijuana. There is also some indication that different types of stressors have different effects on this stress and drug reward association. (AU)

Report of ezootic Angiostronglyus cantonesis from Jamaica [ABSTRACT]

OBJECTIVE: To study the status of infection with Angiostrongylus cantonensis in wild rats and snails in Jamaica following an outbreak of eosinophilic meningitis amongst tourists. METHODS: One hundred and thirty-one Rattus rattus and 94 R norvegicus were collected, mainly from the eastern portion of Jamaica. The animals were dissected and the heart and pulmonary arteries explored to reveal A cantonensis. Similarly, several species of land snails were collected. A portion of the head/foot was excised, fragmented and placed in separate dishes of digestion fluid (0.01 percent pepsin in 0.7 percent v/v aqeous HCI). Dishes were examined for nematode larvae 4-5 hours and 24 hours post-digestion. A microscopical comparison of larvae with museum specimens confirmed identification. RESULTS: Overall, significantly more R rattus (42.7 percent) than R morvegicus (21.3 percent) were infected (x2=11.28;p<0.0001). Considering only those parishes where 15 or more rats were collected (Hanover, Manchester, St.James, St. Elizabeth, Kingston and St.Andrew, and Portland) the prevalence of rodent infections ranged from 6 to 59 percent. Of three snails and one slug species collected, only Thelidomus asper harboured A cantonensis larvae. This snail was collected from Manchester where the highest prevalence of rodent infections also occurred. CONCLUSIONS: The findings indicate that A cantonensis is present in rats and snails in Jamaica. In the context of reports (1996, 2000) of eosinophilic meningitis on the island, we recommend that public health officials, clinical parasitologists and travel medicine practitioners consider A cantonensis as a causative agent of eosinophilic meningitis in residents and travellers to Jamaica. (AU)

The characterization of the activity of a bark extract from Fagara martinicensis on the rat vas deferens

OBJECTIVE: An aqueous extract made from the bark of Fagara martinicensis (family Rutaceae) was examined for its effect on the isolated rat vas deferens. METHOD: The investigation involved measurement of isometric tension in the prostatic and epididymal portions of the isolated rat vas deferens which was anchored in an organ bath with physiological solution. Non-cumulative doses of Fagara martinicensis (FM) were added to the bath and the effects examined in the presence of receptor antagonists to characterize the actions of FM. Results before and after antagonist additions were compared. RESULTS: Non-cumulative addition of FM (1.6 mg/ml to 14.1 mg/ml) produced contractions of both portions of the vas deferens, with the epididymal portion showing greater sensitivity to the effects of FM. The contractions consisted of a rhythmic component superimposed on a phasic and tonic component. All components of the contractions were abolished by prazosin (2.1 uM), a selective a1-adrenoreceptor antagonist, and therefore it was concluded that FM contractions are due to agonist activities on these receptors. Since stimulation of a1-adrenoreceptora results in the mobilization of extracellular calcium into the muscle, the involvement of extracellular calcium was investigated with calcium channel antagonist, nifedipine (0.11-6.0 uM). Nifedipine inhibited all components of the contraction. This effect indicates that entry of extracellular calcium into the muscle was involved in all components of the contraction and further confirms a1-adrenoreceptor agonist action of Fagara martinicensis. CONCLUSIONS: Fagara martinicensis may therefore be a potential source of drugs with a1-adrenoreceptor agonist properties. (AU)

Investigation of the anti-inflammatory properties of leaves of Artocarpus altilis (breadfruit)

OBJECTIVE: The leaves of the breadfruit tree (Artocarpus altilis) are used in folklore medicine in the Caribbean to relieve pain and inflammmation. Our objective was to determine whether there is any scientific basis to this folkloric claim. METHODS: An aqueous decoction of breadfruit leaves (BL) was prepared, and tested for anti-inflammatory activity using the "carrageenan induced rat paw oedema" method. Groups of rats were given doses of BL (15, 30 and 60 mg/kg) and saline (control). Additional experiments were done on isolated guinea pig trachea challenged with acetylcholine (Ach), prostaglandin E2 (PGE2), bradykinin and histamine to investigate the mechanism of action of BL. RESULTS: BL at a dose of 60 mg/kg exhibited significant anti-inflammatory activity (p<0.05) from 0.5 to 4 hours. Lower doses of BL (15 and 30 mg/kg) did not produce any significantly different effects from control (p>0.05). BL antagonized the actions of PGE2 and bradykinin on the trachea but not that of Ach or histamine. CONCLUSION: Our findings suggests that an extract of the breadfruit leaves contains one or more compounds with significant anti-inflammatory properties. However, further studies are required to isolate these compounds and to determine their pharmacological profile. (AU)

Understanding the mechanism of action of Cytochrome c Oxidase in normal and disease states: shark heart enzyme, a potential model

Cytochrome c oxidase, the final member of the electron transport chain, is crucial to respiration and also contributes to the synthesis of cellular ATP. The total absence of this enzyme is incompatible with life and its deficiency or malfunction leads to a number of serious disease states. Understanding the mechanism of action of this enzyme, which is an important prerequisite to unravelling its role in the pathogenesis of disease states, is hampered by the lack of suitable enzyme models. The bovine enzyme, which are structually simple, appear to follow a different mechanism of action. The hammer head shark is a seasonal resident of the warm waters of the Caribbean Sea. The work presented here indicates that, like the bovine enzyme, the enzyme of the heart of this shark (i) possesses thirteen subunits and two substrate binding sites and (ii) exhibits biphasic kinetics. The work also confirms that, unlike the bovine enzyme which is dimeric, the shark enzyme functions as a monomer. Given this latter simplifying feature, in conjunction with its kinetic and structural similarities to the more complex mammalian varieties, we propose that shark heart cytochrome c oxidase replace the bovine and bacterial forms as the enzyme of choice for model studies.(Au)

Salt-Induced hypertension in rats alters the response of isolated aortic rings to cromakalim

The effect of cromakalim, an opener of ATP-sensitive potassium (K atp) channel, on precontracted aortic rings from control and salt-loaded rats was studied in spague-Dawley rats. Salt-loading experiments involved the induction of hypertension by 6-week feeding of 80 g sodium chloride(NaCl)per kilogram(kg) diet while the control diet had 3 g NaCl per kg diet. Blood pressure and heart rate were determined by cannulation of a femoral artery under urethane/a-chloralose anaesthesia. Isolated aortic rings were mounted in tissue baths for isometric tension measurement. The sodium-potassium adenosine triphosphstase (Na-KATPase) pump activity was measured by potassium(K)-induced relaxation (with or without ouabain) following precontraction with 10-7 M noradrenaline.The KATP channel was studied by measuring the relaxation response to cromakalim,precontracted with either 10-7M noradrenalineor 60mM potassiumchloride(KCl). The Na- k ATPase pump appeared to be inhibited during salt loading. ATPase inactivation was found to be ouabain sensitive but did not seem to affect subsequent K - induced contraction. Cromakalim produced relaxation of noradrenaline precontracted rings frem the control rats; rings from salt-loaded rats showed significantly less relaxtion than control(p<0.05) under similar conditions. During K-induced precontraction, cromakalim produced a weak biphasic response in the control rings-an initial relaxation and then a reversal. Cromakalim produced further contraction of K-induced precontraction in salt-loaded group. The results suggest that ATP-sensitive potassium channels and Na-K ATPase pumps on the vascular smooth muscle membrane may be deactivated in the development of hypertension during salt loading.(AU)

The effects of chronic S-nitrosoglutathoine adminstration on glucose tolerance in dog animal model

The nitric oxide donor S-nitrosoglutathione (GSNO) has been used to prevent platelet activation in patients with severe pre-eclampsia. The study assesses the chronic administration of GSNO on glucose metabolism in the dog animal model. GSNO (10 mg/kg) was administered intravenously for 14 days and the blood glucose concentration was determined by the glucose oxidase method. Oral glucose tolerance tests revealed an impaired glucose tolerance in the GSNO-treated dogs as reflected by elevated postprandial blood glucose concentrations at the 1.0 hour to 2.5 hour time interval (p < 0.05). The elevated blood glucose concentration was associated with a statistically significant decrease in plasma insulin concentration. The plasma insulin concentration at 1.0 hour in captopril-treated controls was 41.00 uIU/ml compared with 27.33 uIU/ml in GSNO-treated dogs (p < 0.05). In contrast, the plasma glucagon concentration was enhanced by the chronic adminstration of GSNO, as confirmed by a concentration of 75.00 ñ 6.06 pg/ml in GSNO-treated dogs compared with 49.50 ñ 4.64 pg/ml in captopril-treated controls at the 1.0 hour time interval. Linear regression analysis of the data revealed a highly significant and positive correlation between the blood glucose concentration and the plasma glucagon concentration (r = 0.739, p < 0.01). Similarly, a positive correlation existed between the blood glucose concentration and the plasma insulin concentration (r = 0.513, p = 0.307). We conclude that chronic in vivo adminstration of GSNO impairs the parameters of carbohydrate metabolism. Patients who are on protracted treatment with GSNO could be risk for the development of diabetes mellitus.(Au)

The feasibility of a porcine model of acute coronary occlusion and reperfusion using off-pump coronary artery bypass grafting

We developed an open-chest porcine model of acute coronary occlusion and surgical reperfusion, and attempted to prevent intra-operative ischaemic ventricular fibrillation (VF) by a Retrograde Intracoronary Glyceryl trinitrate (RIG) infusion into the occluded vessel. Five Yorkshire pigs (weight 50ñ 1.1kg), randomized into 3 groups, underwent median sternotomy under general anaesthesia. One pig (Group 1, control) underwent sternotomy and pericardiotomy only. Four pigs underwent acute left anterior descending (LAD) coronary occlusion. Two pigs were not reperfused (Group 2). Two pigs underwent surgical reperfusion (Group 3) via left internal mammary artery (LIMA) grafting to the LAD using the Off-Pump Coronary Artery Bypass (OPCAB) technique. Ischaemic injury was assessed using 7-lead electrocardiography (EGG) and transthoracic/epimyocardial echocardiography (ECHO). Group 1: transient intraoperative hypotension and VF occurred. Successful resuscitation and 10-week survival (until sacrifice) with normal left ventricular (LV) function was achieved. Group 2: there were ECG and ECHO evidence of acute LV ischaemic dysfunction in both pigs. The surviving pig had persistent anterior hypokinesis at 8« months. The other died intra-operatively following progressive ischaemic LV dysfunction despite resuscitative attempts. Group 3: the surving pig had normal LV function at 8 months. Initial anterior LV akinesis normalized within 7 days. The other developed post-occlusion haemodynamic instability and died intra-operatively despite reperfusion. In this porcine model, acute LAD artery occlusion modified by the novel RIG infusion technique, followed by surgical reperfusion (OPCAB) is feasible. This model would facilitate further development of OPCAB surgical expertise and understanding of the pathophysiology of ischaemia-reperfusion injury.(Au)