Quantitative ultrastructure of synapses on functionally identified primary afferent neurons in the cat trigeminal mesencephalic nucleus

Though a number of studies have reported the presence of synapses on neurons in the trigeminal mesencephalic nucleus (Vmes), there have been no quantitative studies of either the density of innervation, or the ultrastructure, of the synapses on single, physiologically identified neurons in this nucleus. In this study we recorded from single neurons in the Vmes, identified them as being either muscle spindle afferents (MS) or periodontal ligament mechanoreceptor afferents (PL), and then labeled the neurons by intra-axonal injection of horseradish peroxidase (HRP). The material was first processed to reveal the HRP activity, following which ultrathin sections through the labeled somata were cut and examined under the electron microscope. Complete serial reconstructions were made through the soma of one MS neuron and one PL neuron, and the contacts on the neurons reconstructed. Boutons were found on the soma, spines, appendages and the axon hillock and the initial segment of the axon. The numbers of boutons terminating on the two neurons were 198 (PL) and 424 (MS), giving a packing density of 4.4 and 10.7 boutons respectively (i.e., number of boutons/100 micron 2 of the postsynaptic membrane). Boutons could be separated into two types on the basis of their vesicles: those containing clear, round vesicles (i.e., S-type) and those containing a mixture of round, oval and flattened vesicles (P-type). Ninety-five (PL neuron) and 99% (MS neuron) of terminals on the two neurons were P-type. All the S-type boutons and 80% of the P-type boutons formed asymmetric synaptic contacts while 10% of the P-type boutons made symmetric contacts. Quantitative measurements of the P-type boutons on the labeled neurons, in which the data of MS and PL neurons were pooled, revealed that bouton volume was highly correlated with bouton surface area, active zone number, total active zone area, vesicle number, and mitochondrial volume. However, comparing the quantitative measurements of the P-type boutons with those of previously reported vibrissa afferent terminals and their associated axon terminals revealed that all the parameters were smaller for the P-type boutons (on Vmes neurons) than those of the vibrissa afferent terminals but similar to those of axon terminals presynaptic to the vibrissa afferents. Taken together, our results emphasize the wide scope for synaptic interactions in the Vmes and suggest that it may be more fruitful to view the Vmes as an integrating center.     

Phone-Based Intervention under Nurse Guidance after Stroke (PINGS II) Study: Protocol for a Phase III Randomized Clinical Trial

ObjectivesThe Sub-Saharan African (SSA) region now has the highest estimated effect size of hypertension for stroke causation worldwide. An urgent priority for countries in SSA is to develop and test self-management interventions to control hypertension among those at highest risk of adverse outcomes. Thus the overall objective of the Phone-based Intervention under Nurse Guidance after Stroke II study (PINGS-2) is to deploy a hybrid study design to assess the efficacy of a theoretical-model-based, mHealth technology-centered, nurse-led, multi-level integrated approach to improve longer term blood pressure (BP) control among stroke survivors.Materials and methodsA phase III randomized controlled trial involving 500 recent stroke survivors to be enrolled across 10 Ghanaian hospitals. Using a computer-generated sequence, patients will be randomly assigned 1:1 into the intervention or usual care arms. The intervention comprises of (i) home BP monitoring at least once weekly with nurse navigation for high domiciliary BP readings; (2) medication reminders using mobile phone alerts and (3) education on hypertension and stroke delivered once weekly via audio messages in preferred local dialects. The intervention will last for 12 months. The control group will receive usual care as determined by local guidelines. The primary outcome is the proportion of patients with systolic BP <140 mm Hg at 12 months. Secondary outcomes will include medication adherence, self-management of hypertension, major adverse cardiovascular events, health related quality of life and implementation outcomes.ConclusionAn effective PINGS intervention can potentially be scaled up and disseminated across healthcare systems in low-and-middle income countries challenged with resource constraints to reduce poor outcomes among stroke survivors.     

Gamma scintigraphic evaluation of film-coated tablets intended for colonic or biphasic release

The gastrointestinal transit and in vivo drug release behaviour of a film-coated tablet formulation was investigated in five healthy human subjects using the technique of gamma scintigraphy. The film coating system consisted of a mixture of pectin, chitosan and HPMC in a ratio of 6:1:0.37 applied to 750 mg cores at a coat weight gain of 9%. The estimated mean values of the gastric emptying time (62±17 min), small intestinal transit time (219±53 min), ileocaecal junction lag time (79±30 min) and the colon arrival time (345±33 min), were similar to published values for the transit of similar sized tablets in humans. The amount of radioactive tracer released from the labelled tablets was minimal when the tablets were in the stomach and the small intestine. There was increased release of radioactivity when the tablets were in the colon due to increased degradation of the film coatings by pectinolytic enzymes resident in the colon. The pectin/chitosan/HPMC film coating system thus acts as a colonic delivery system.     

Schistosomiasis control in Ghana: case management and means for diagnosis and treatment within the health system

An essential component of integrated schistosomiasis control as promoted by WHO is adequate clinical care for patients presenting at health care facilities. We evaluated the functioning of the Ghanaian health system for diagnosis and treatment of schistosomiasis by interviewing health workers from 70 health care facilities in 4 geographical areas in April and May 2000. Results from presentation of 4 hypothetical cases and a subsequent interview demonstrated that patients presenting with symptoms related to schistosomiasis have a small chance of receiving adequate treatment: often health workers do not recognize the symptoms, especially those of Schistosoma mansoni; patients are frequently referred for a diagnostic test or treatment with a large risk of non-compliance; and praziquantel was not available in 78% of the health care facilities with reported schistosomiasis in their coverage area. The overall cost of treatment is considerable: [symbol: see text] 2.13 for S. haematobium and [symbol: see text] 1.81 for S. mansoni patients, with drug costs contributing approximately 40% of the total cost. To better meet WHO recommendations for passive case detection as part of integrated schistosomiasis control, the Ghanaian health system needs to emphasize training of health workers in schistosomiasis case recognition and case management and increase the availability of praziquantel. Experience from other West African countries indicate that this is feasible.     

Leaching of pectin from mixed films containing pectin,chitosan and HPMC intended for biphasic drug delivery

Mixed films containing pectin, chitosan and HPMC, prepared by solvent casting from 0.1 M HCl (pH 1.5) and 0.1 M acetic acid (pH 2.9) were evaluated for their morphological and leaching properties. Films cast at pH 1.5 were uniform with smooth surfaces while films cast at pH 2.9 showed particle aggregation and had rough surfaces due to polyelectrolyte complex (PEC) formation between pectin and chitosan in the medium. The leaching of pectin was higher from films at cast pH 1.5 due to the absence of PEC formation. Pectin leaching was controlled in simulated upper gastrointestinal conditions but was accelerated in the presence of pectinolytic enzymes. The leaching of pectin from the mixed films was a function of the pH of the film casting solvent, pH of the incubation medium, PEC formation and HPMC content.     

Applicability of a monoclonal antibody-based dipstick in diagnosis of urinary schistosomiasis in the Central Region of Ghana

Summary We tested a rapid visually read monoclonal antibody (MoAb) based dipstick assay for specific diagnosis of urinary schistosomiasis against microscopy and the use of haematuria and proteinuria in a schistosomiasis haematobia endemic area in the Central Region of Ghana. The study group consisted of 141 school children (83 males, 58 females) aged 8-19 years. A total of 129 of 141 (91.5%) submitted stool samples, and 7.8% had Schistosoma mansoni, 55% had hookworms and 6.2% had tapeworms. The presence of S. mansoni and intestinal parasites did not appear to influence the results of the MoAb-dipstick assay. The urinary schistosomiasis prevalence by MoAb-dipstick (78%) was higher (P < 0.05) than the estimate by microscopy (60.3%), microhaematuria (27%) and proteinuria (30.5%). The MoAb-dipstick correctly identified 98.8% of microscopically confirmed cases and missed one (1.3%). The dipstick was also positive for 26 of 56 (46.4%) egg-negative individuals, thereby giving a sensitivity of 98.8% and a specificity of 53.6%. On the other hand, microhaematuria and proteinuria were 38.8% and 30.6% sensitive, and 91.1% and 69.6% specific, respectively. Microhaematuria and proteinuria were less sensitive (P < 0.05) than both microscopy and MoAb-dipstick.     

Differences in monosynaptic EPSPs elicited by masseter and temporalis spindle afferents in anaesthetised rats

We have used the intracellular variant of the spike triggered averaging method to examine the monosynaptic connexions of masseter and temporalis spindle afferents on jaw-elevator motoneurones. Temporalis spindle afferents elicited larger averaged EPSPs in motoneurones than masseter spindle afferents, in part because transmission at synapses of temporalis afferents was associated with lower incidences of failures. We conclude that EPSP amplitude in this motor system is governed, at least in part, by the presynaptic neurone rather than the identity of the postsynaptic neurone.