Myasthenia gravis and neuromyelitis opica: A causal link.

Neuromyelitis Optica (NMO) and Myasthenia Gravis (MG) are rare antibody mediated disorders of the central nervous system (CNS) and neuromuscular junction (NMJ) respectively. Both diseases are predominantly mediated by IgG1 antibodies that activate complement. There have been increasing reports of patients who develop both disorders. Given the rarity of both diseases it would seem that these occurrences are not purely coincidental. There is heterogeneity between the cases described in the literature but common trends are observed in patients who develop both disorders. Most patients described are female. Typically the MG precedes the NMO and the majority of patients have undergone thymectomy. Generally, the symptoms of MG are mild but the NMO tends to follow a more aggressive clinical course. The pathogenesis of NMO in combination with MG is unknown, but thymectomy has been implicated in a subset of patients. We present the case of a female patient who developed NMO on a background of sero-positive MG and discuss the relevant literature.

Screening of dogs for Echinococcus granulosus coproantigen in a low endemic situation in Cyprus.

In the framework of an echinococcosis surveillance and control programme in Cyprus, a commercial enzyme-linked immunosorbent assay (ELISA) (CHEKIT ECHINOTEST) designed for the detection of Echinococcus granulosus and E. multilocularis coproantigens was used in 1997-2000 for the investigation of large numbers of dogs. Most of the animals originated from areas where approximately 0.2% of the dogs had been found to be infected with E. granulosus in previous (1993-1996) arecoline surveys. The sensitivity of the coproantigen test was 83%, as determined in 35 dogs naturally infected with this cestode species. The specificity was 98% in 97 randomly selected dogs from Cyprus, but it was reduced to 80% in a group of 50 dogs, infected with Taenia spp. A total of 6551 dogs (mainly of rural origin) was examined, including three large groups (N: 2928, 1761 and 1800) from the Government Control Area (GCA) in southern Cyprus and a small group (N: 62) from the Non-Government Control Area (NonGCA) in the northern part of the island. Among the dogs from the GCA, 184 (2.8%) tested positive for coproantigen; coproantigen prevalences were 2.6, 4.9 and 1.1% in these three groups, and of 62 dogs from the NonGCA 8.1% were positive. The calculated true prevalences of E. granulosus in the dog population of the GCA ranged between 0.0 and 3.58%. The predictive values of the test, based on a 0.2% prevalence, was >99.9% for negative results, but very low (7%) for coproantigen-positive results. However, the relatively small number of coproantigen-positive dogs can be treated with praziquantel or the results can further be confirmed by arecoline purging.

Evaluation of control programmes for echinococcosis/hydatidosis in Cyprus.

In Cyprus, echinococcosis (Echinococcus granulosus) was an important public and animal health problem until the 1970s. In 1971, the Department of Veterinary Services instigated a control programme, which was based on an island model, using arecoline testing, euthanasia of positive dogs, control of dog breeding, elimination of stray dogs and control measures in slaughterhouses. The first programme ended in 1985 with excellent results and E. granulosus was considered to have been eradicated from both the definitive hosts (dogs) and the intermediate hosts (livestock). However, surveillance from 1985 to 1993 demonstrated that the life-cycle of E. granulosus was continuing at very low levels. Control measures were therefore reintroduced in 1993. The second programme commenced in 1993 and was based on surveillance of intermediate hosts, control of infected flocks, and testing and treatment of owned and stray dogs in infected areas. A continental model was employed for the second programme, due to the division of the island in 1974. The experience gained from the two programme is described.

Canine leishmaniosis in Cyprus due to Leishmania infantum MON 1.

During a serological survey in 1996, a total of 601 dogs (group I) distributed all over the government controlled southern area of Cyprus was examined using an enzyme-linked immunosorbent assay (ELISA) for the presence of specific antibodies directed against soluble antigens of promastigote stages of Leishmania infantum. The overall seroprevalence rate in this group was 1.7%. A second group (group II) of dogs was selected from regions where seropositive dogs where determined within the first group. In group II specific anti-Leishmania antibodies could be detected in 30 of 301 dogs investigated (10%). The highest seroprevalence rates were found in the regions of Agios Georgios (26.2%) and Limnatis (12.2%). Ten parasite isolates from ten dogs (six with typical symptoms of canine leishmaniosis and four without symptoms) originating from five locations could be characterised by zymodeme analysis. All ten isolates were identified as L. infantum zymodeme MON 1.

Control of Echinococcus granulosus in Cyprus and comparison with other island models.

A control programme directed against Echinococcus granulosus was introduced into the Republic of Cyprus in 1971. In 1974, this was restricted to the areas controlled by the government of the island. The force used in the 'attack' phase included a major dog control programme. This and other measures led to the rapid 'disappearance' of the parasite and control was terminated in 1985. Subsequent studies during 1993-1996 revealed that the parasite was present in 82 (20%) villages in either dogs or food animals or both and control was re-introduced in the 'consolidation' phase with emphasis on the surveillance of E. granulosus in intermediate hosts, animal movement control and treatment of dogs in 'infected' villages. During these surveys, a major difficulty was found to be in determining whether transmission was autocthonus or introduced by animals from the areas not controlled by the government. Evidence was found to suggest the former was the most likely for the infected animals which had been born and reared far from the dividing line in the government-controlled area. A major contribution of this and other island programmes, such as those in Iceland, New Zealand, Tasmania (Australia) and the Falkland Islands, to an understanding of control planning has been the demonstration that it cannot readily be determined when eradication has been achieved and that once the costly 'attack' phase has been converted into the much more cost-effective 'consolidation' phase this must be maintained indefinitely in that phase if there is cross-border transmission as is likely to be the case in all Continental control programmes.

Subthreshold synaptic activation of voltage-gated Ca2+ channels mediates a localized Ca2+ influx into the dendrites of hippocampal pyramidal neurons.

1. Whole cell recordings and high-speed fluorescence imaging were used to investigate the spatial and temporal characteristics of Ca2+ influx during synaptic activity in hippocampal CA1 pyramidal neurons. Brief, subthreshold trains of synaptic potentials elicited by Schaffer collateral stimulation produced transient increases in [Ca2+]i in the apical dendrites near the site of synaptic input. The rises in [Ca2+]i were not due to Ca2+ entry through N-methyl-D-aspartate (NMDA)-activated or non-NMDA-activated glutamate channels, but were reduced by low concentrations of Ni2+. Hyperpolarizing prepulses caused an increase in the synaptically evoked Ca2+ transients, whereas strong hyperpolarization during the train prevented the rise in [Ca2+]i. The data suggest that subthreshold synaptic activity can open low-voltage-activated (T-type) Ca2+ channels and produce a local increase in intradendritic [Ca2+]. Such local increases in [Ca2+]i may be important for modulating the strength of synaptic connections.

Changes in extracellular and rat brain tissue concentrations of D-beta-hydroxybutyrate after 1,3-butanediol treatment.

1,3-Butanediol (BD) treatment was previously shown to produce a dose-related increase of the plasma levels of D-beta-hydroxybutyrate (BHB) and to protect brain tissue against hypoxia and ischemia. The purpose of this study was to test whether BD-induced hyperketonemia was associated with changes in brain extracellular and tissue concentrations of BHB. Changes in extracellular levels of BHB were continuously monitored in anesthetized rats before and after intraperitoneal injection of BD (25 mmol/kg), using intracerebral microdialysis coupled to online analysis of BHB in the dialysate. Cortical tissue concentrations of BHB were determined in control and BD-treated rats (25 and 50 mmol/kg, i.p.) after freezing of the brain in situ. Butanediol produced a rapid increase in dialysate levels of BHB, with a linear relationship between dialysate and plasma BHB concentrations (r = 0.81, p < 0.001). In contrast, and although brain tissue levels of BHB were markedly increased after BD treatment, they were not related to the plasma concentration of BHB. Our results suggest that BHB produced from BD did not accumulate in brain and that BD protects against hypoxia or ischemia by increasing brain BHB availability.

The postsynaptic induction of nonassociative long-term depression of excitatory synaptic transmission in rat hippocampal slices.

1. Long-term depression (LTD) is an activity-dependent reduction in the strength of synaptic transmission that can persist for hours. It is a neural model for processes underlying learning and memory, such as extinction and forgetting. LTD of excitatory postsynaptic potentials (EPSPs) in cells of the CA1 region of hippocampal slices can be induced in an anti-Hebbian paradigm, i.e., by conditioning stimuli that activate the postsynaptic neuron in the absence of evoked synaptic transmission in the test pathway. Past work showed that LTD was not produced consistently in a pharmacologically untreated slice, but it could be induced more reliably when the conditioning stimuli were applied during block of evoked transmitter release. We have now defined further the conditions in which LTD can be obtained using postsynaptic conditioning by investigating 1) whether intracellular conditioning is effective, 2) the requirement for extracellular Ca2+, and 3) the consequences of selective block of glutamate ionotropic receptor subtypes during the conditioning procedure. 2. Intracellular recordings were made from CA1 pyramidal neurons. Test shocks were applied to the stratum radiatum except during conditioning, and the depolarizing slopes and amplitudes of evoked EPSPs were measured. The conditioning procedure activated the postsynaptic neuron either antidromically (via trains of shocks at 100 Hz applied to the axons in the alveus) or intracellularly (via depolarizing pulses of 1.5-3.5 nA). During conditioning, postsynaptic potentials (PSPs) evoked by the conditioning stimuli either were transiently blocked by bathing slices for 5 min in artificial cerebrospinal fluid (CSF) containing a high [Mg2+] or were reduced by glutamate antagonists. 3. When slices were bathed in CSF containing 25 mM Mg2+ and 2 mM Ca2+, evoked PSPs were transiently abolished; conditioning, either by antidromic or intracellular stimulation, always evoked a significant LTD. During the LTD produced by antidromic stimulation, the mean EPSP slope was 52.6 +/- 11.4% (mean +/- SE) of its control at 30-35 min after conditioning (n = 7). The LTD produced by intracellular conditioning was of similar magnitude: the mean EPSP slope was 57.2 +/- 11.6% of its control at 30-35 min postconditioning (n = 7). When slices were bathed in CSF containing 25 mM Mg2+ and 2 mM Ca2+ without conditioning stimuli, there was no LTD (mean EPSP slope 109 +/- 8.1% of its control at 30-35 min after reperfusion with CSF; n = 5).(ABSTRACT TRUNCATED AT 400 WORDS)

Investigation of beta-adrenergic modulation of synaptic transmission and postsynaptic induction of associative LTP in layer V neurones in slices of rat sensorimotor cortex.

Long-term potentiation (LTP) of synaptic transmission is considered to be a neuronal model of learning. Recently, the probability of induction of associative LTP in layer V cells in sensorimotor neocortex was shown to be much higher in the awake cat than in the slice preparation. We hypothesised that the loss of extrinsic noradrenergic activity in the slice might account for this difference, particularly since a beta-adrenergic enhancement of field potentials has been seen in this preparation. We therefore bath-applied noradrenaline (NA) or the beta 1-adrenergic agonist, isoprenaline (ISO) to elucidate the cellular basis of the enhancement of field potentials, and to see if the drugs increased the probability of induction of associative LTP in slices. We found that NA and ISO produced a dose-dependent, reversible reduction of spike accommodation and an increase in excitability but had no effect on the depolarizing slope or peak amplitude of sub-threshold EPSPs, and that drug application did not increase the probability of induction of LTP. We conclude that: (1) the enhancement of field potentials and late components of EPSPs (7) can be explained by the known actions of beta-adrenergic drugs on membrane currents in layer V cells, and (2) the lower probability of induction of associative LTP in slices cf. the awake cat cannot be due solely to the loss of noradrenergic activity.

Simple staining for heat-fixed brain sections after topographical pH analysis or autoradiographic studies.

Powerful topographic techniques are now available, among which autoradiographic and fluorescent mapping are the most prevalent. These techniques produce images that usually do not correlate with brain anatomy; subsequent staining is required to allow a precise association between the parameter(s) investigated and brain structures. A simple staining procedure is described, compatible with heat-fixed brain sections, and that was found particularly valuable in association with topographical tissue pH studies using the fluorescent pH indicator umbelliferone.