Patient perceptions of a tuberculosis testing program provided in the community pharmacy setting.

OBJECTIVES: This study sought to describe patient experiences and perceptions of a public health initiative designed to improve tuberculosis (TB) testing access using the tuberculin skin test (TST) in a community pharmacy setting. STUDY DESIGN: This was a cross-sectional study. METHODS: A telephonic survey of patients who had received a TST at one of twelve participating community pharmacies between August 2014 and July 2016 was conducted. The 26-question survey was developed by two pharmacists with expertise in TB management and one pharmacy student. Before administration the survey was peer-reviewed for clarity. Potential study patients were identified through TST records at the study pharmacies. English-speaking patients older than 18 years were eligible for study inclusion. Statistical differences in responses based on location were identified using chi-squared test for frequency comparisons with a P-value of <0.05 to determine statistical significance. RESULTS: A total of 1709 patients received a TST during the study period, of whom 431 were contacted and 325 participated, meeting the predetermined representative sample needed of 314 patients. The majority of study patients were female (67.1%) and white (81%). The mean age was 36 years (standard deviation = 14.1). A majority (68.3%) lived <5 miles from the TST pharmacy, while 45.2% of those with a primary care provider (PCP) (61.6% of respondents) lived within 5 miles of the PCP's office. Care was accessible and met patients' testing needs. For most patients (84.6%), the initial and follow-up appointments took < 20 min. Follow-up TST reading rate was 98.5%; 4.3% of tests were positive. Positive TST results were associated with use of a small city pharmacy (P = 0.003). Perception differences based on location were identified. CONCLUSIONS: Uptake of the TST service in the community pharmacy setting was high and patients reported positive experiences.

Mutual coupling between the ocular circadian pacemakers of Bulla gouldiana.

The ocular circadian pacemakers of Bulla gouldiana were found to be mutually coupled, and their interaction could be observed in an isolated nervous system maintained in vitro. Experimentally induced phase separations between the two ocular pacemakers were reduced when the eyes were allowed to interact for 48 hours. The reduction in phase separation did not occur however when the cerebral commissure was severed, indicating that this neural tract is a critical pathway coupling these two circadian clocks.

Comparison of post-marketing surveillance approaches regarding infections related to tumor necrosis factor inhibitors (TNFi's) used in treatment of autoimmune diseases.

Objectives: To examine agreement between the FDA Adverse Event Reporting System (FAERS) and observational studies in common infections for tumor necrosis factor inhibitors (TNFi's). Methods: Using MedDRA® preferred terms, all infection cases in FAERS with each TNFi were retrieved using EvidexTM. Observational studies reporting TNFi-related infections were identified from PubMed (OS-PM) and ClinicalTrials.gov (OS-CT). Infections with a reporting rate of ≥2% (based on percentage of total number of infections) from each data source were compiled. Fleiss's kappa and Cohen's kappa (κ) were calculated to determine agreement across all three sources and between each two sources. Results: A total of 163,789 FAERS infection cases, 53 OS-PM studies and 52 OS-CT studies were identified. The Fleiss' kappa that comparing all 3 data sources demonstrated lack of agreement. Significant moderate agreements were found between FAERS and OS-CT for etanercept and adalimumab, respectively (κ = 0.53, p = 0.02; κ = 0.56, p = 0.02), but no agreements (κ < 0) when comparing FAERS vs. OS-PM or OS-CT vs. OS-PM. Conclusion: For common TNFi-related infections, passive (FAERS) and active (observational studies) pharmacovigilance results are similar between FAERS vs. OS-CT for etanercept and adalimumab but dissimilar across the 3 sources. Our findings suggest incorporating both active and passive pharmacovigilance methods in post-marketing drug safety assessment.

Economic evaluations of fluticasone-propionate/salmeterol combination therapy for chronic obstructive pulmonary disease: a review of published studies.

This review identifies and evaluates the comprehensive reporting of peer-reviewed economic evaluations of the effectiveness of fluticasone-propionate/salmeterol combination (FSC) therapy for maintenance treatment of chronic obstructive pulmonary disease (COPD). Economic evaluations were included if published in English since 2003. Evaluation categories included in the review were cost-effectiveness, cost-utility, and cost-consequence analyses. FSC is cost-effective in comparison to short-acting bronchodilators (SABDs). Cost and outcome differences between FSC and other long-acting therapies were modest. Studies exhibited large variations in populations, designs and environment, limiting the ability to draw conclusions. Many new maintenance treatments for COPD have been approved since 2010. Most have yet to be compared to older treatments like FSC. Evaluations are needed that consider costs and outcomes from a societal perspective (e.g., patients' ability to keep working) and evaluations that include subgroup analyses to investigate differential impacts according to clusters of patient characteristics.

Cell surface charge correlation of partition with electrophoresis.

Critical mixtures of aqueous solutions of polymers separate into two or more immiscible phases. Particulate materials distribute in such phase systems generally between one bulk phase and the interface between bulk phases. The distribution is described by a simple partition law, and is quantitatively determined by, inter alia, the nature of the particle surface, particularly net electrical charge. The partition behaviour of various cells, native or modified by treatment with trypsin, neuraminidase or maleic anhydride, correlate strongly with electrophoretic mobility. Partition behaviour and electrophoretic mobility are both dependent upon cell surface charge. Thus, in appropriate conditions, changes in surface charge may be registered as changes in partition.

Analysis of mutual circadian pacemaker coupling between the two eyes of Bulla.

The eyes of Bulla, a marine snail, express a circadian rhythm in the frequency of optic nerve compound action potentials (CAPs). The two ocular pacemakers are mutually coupled, and their interaction can be observed in vitro. The evidence for mutual coupling, as demonstrated in the present experiments, was as follows: (1) When intact Bulla were placed into darkness for up to 72 days, the two pacemakers did not desynchronize. (2) The free-running period of the ocular rhythm in the intact system (24.4 hr) was longer than the free-running period of the rhythm recorded from isolated eyes (23.7 hr). (3) When the two ocular pacemakers were experimentally desynchronized in vitro, resynchronization occurred if the pacemakers were allowed to interact for 48 hr. The coupling signals are most likely the CAPs. These impulses are conducted through the central ganglia and emerge as efferent impulses in the opposite optic nerve. Ocular-derived efferent impulse activity affects spontaneous impulse production in the target eye and alters the waveform of the circadian rhythm. The coupling pathway mediating syncrhonization consists of the two optic nerves, the cerebral ganglia, and the cerebral commissure. The demonstration of coupling in vitro provides a new opportunity for studying the cellular mechanisms underlying mutual pacemaker entrainment.

Cellular analysis of ocular circadian pacemaker coupling in Bulla: role of efferent impulses in phase shifting.

The eyes of Bulla gouldiana, a marine snail, contain circadian oscillators that are coupled to each other. Obvious candidates for the coupling signals are the optic nerve compound action potentials (CAPs) that express the circadian rhythm and lead to efferent impulses in the contralateral optic nerve. In the present experiments, the role of the CAPs as coupling signals was evaluated. We found that, following desynchronization of the two ocular oscillators by phase-delaying one eye with manganese, subsequent phase shifts in the initially unshifted ocular rhythm only occurred during the time that efferent optic nerve signals were present. In addition, in the absence of ocular desynchrony, phase shifts of the ocular rhythm could still be effected by activation of the efferent pathway. The influence of efferent impulses on identified retinal cells was also evaluated. No effect of efferent signals on receptor layer cells was detected, while it was found that efferent impulses generated depolarizations in basal retinal neurons (BRNs), the putative circadian oscillator cells. Depolarization of the BRNs has been shown previously to be involved in the light entrainment pathway. Depolarization appears to be similarly involved in the coupling pathway, since membrane depolarizations that mimicked the efferent-induced postsynaptic potentials likewise generated phase shifts of the ocular rhythm.

Biocompatibility of single-walled carbon nanotube composites for bone regeneration.

OBJECTIVES: The purpose of this study was to evaluate in vivo biocompatibility of novel single-walled carbon nanotubes (SWCNT)/poly(lactic-co-glycolic acid) (PLAGA) composites for applications in bone and tissue regeneration. METHODS: A total of 60 Sprague-Dawley rats (125 g to 149 g) were implanted subcutaneously with SWCNT/PLAGA composites (10 mg SWCNT and 1gm PLAGA 12 mm diameter two-dimensional disks), and at two, four, eight and 12 weeks post-implantation were compared with control (Sham) and PLAGA (five rats per group/point in time). Rats were observed for signs of morbidity, overt toxicity, weight gain and food consumption, while haematology, urinalysis and histopathology were completed when the animals were killed. RESULTS: No mortality and clinical signs were observed. All groups showed consistent weight gain, and the rate of gain for each group was similar. All groups exhibited a similar pattern for food consumption. No difference in urinalysis, haematology, and absolute and relative organ weight was observed. A mild to moderate increase in the summary toxicity (sumtox) score was observed for PLAGA and SWCNT/PLAGA implanted animals, whereas the control animals did not show any response. Both PLAGA and SWCNT/PLAGA showed a significantly higher sumtox score compared with the control group at all time intervals. However, there was no significant difference between PLAGA and SWCNT/PLAGA groups. CONCLUSIONS: Our results demonstrate that SWCNT/PLAGA composites exhibited in vivo biocompatibility similar to the Food and Drug Administration approved biocompatible polymer, PLAGA, over a period of 12 weeks. These results showed potential of SWCNT/PLAGA composites for bone regeneration as the low percentage of SWCNT did not elicit a localised or general overt toxicity. Following the 12-week exposure, the material was considered to have an acceptable biocompatibility to warrant further long-term and more invasive in vivo studies. Cite this article: Bone Joint Res 2015;4:70-7.

The antinociceptive effects of stimulating the pretectal nucleus of the rat.

Changes in the tail-flick latency to noxious heat were studied following electrical stimulation of the dorso-medial thalamus of the rat. Brief (15 sec), low intensity (35 microA) stimulation of the anterior pretectal nucleus caused no escape behavior or motor deficits but increased tail-flick latency for more than 45 min. Responses to non-noxious stimuli were enhanced but the animals were not hyperactive. The anterior pretectal nucleus does not receive retinal or accessory visual inputs like other parts of the pretectal complex but is known to receive axons from somatosensory cortex and project to the perirubral mesencephalic reticular formation and the periaqueductal gray (PAG). The antinociceptive effects of anterior pretectal stimulation were much longer lasting than those of PAG, less disrupting to motor performance and the stimulation was not aversive.

The anterior pretectal nucleus: a proposed role in sensory processing.

Four nuclei of the pretectal complex, the olivary pretectal nucleus, the medial pretectal nucleus, the nucleus of the optic tract and the posterior pretectal nucleus, all have a demonstrated role in visual function. In contrast, the anterior pretectal nucleus (APtN) has no inputs from retina and has few outputs to visual accessory nuclei. The APtN has connections with areas associated with sensory functions and it has been suggested that this nucleus may have a role to play in somatosensory processing. An increasing number of behavioural and electrophysiological studies support this view. Brief low-intensity electrical or chemical stimulation of the APtN causes antinociception in the tail flick test in both unanaesthetised and anaesthetised animals. This inhibition of the tail flick response is attenuated by naloxone, alpha-adrenoceptor antagonists and muscarinic cholinergic receptor antagonists. Electrical stimulation of the APtN is similarly effective in the paw pressure and formalin tests. APtN stimulation also causes a brief inhibition of the tooth pulp-evoked jaw opening reflex. studies with [C14]2-deoxyglucose indicate that peripheral noxious stimuli will cause an increase in metabolic activity within the APtN. Animals with electrodes placed in the APtN will self-administer electrical stimulation and this can reduce the aversive and autonomic effects of stimulating the ventromedial hypothalamus. Part of the antinociceptive effects of stimulating the APtN are due to a descending inhibition of spinal dorsal horn projection neurones. Multireceptive neurones deep in the dorsal horn are inhibited by APtN stimulation. In contrast, superficial projection neurones that respond to intense cutaneous stimuli are excited by APtN stimulation. The APtN receives an excitatory input from low-threshold afferents via the dorsal column pathway and a high-threshold excitatory drive from superficial cells projecting through the dorsolateral funiculus. The excitatory input from the dorsal columns may well participate in the long-term inhibition of spinal projection neurones evoked by dorsal column stimulation. These ascending excitatory pathways may also be important to the long-term activation of descending inhibition from the APtN.

The antinociceptive effects of anterior pretectal stimulation in tests using thermal, mechanical and chemical noxious stimuli.

Four behavioural tests have been used to study the antinociceptive effects of electrical stimulation of the anterior pretectal nucleus (APtN) in the rat. The antinociceptive effects of stimulating this nucleus, which lies dorsally in the posterior diencephalon, have recently been studied extensively but always using briefly applied heat stimuli. It is reported here that APtN stimulation effectively inhibited responses to briefly applied noxious pressure and longer-lasting noxious chemical (formalin) stimuli. Although the tail-flick reflex to noxious heat was very potently depressed by APtN stimulation, responses to noxious heat in the hot-plate test were not. Three doses of morphine were also studied with each test and it was concluded that 15 sec of 35 microA r.m.s. current into the APtN was as effective as 3-5 mg/kg morphine s.c. in the rat.

The behavioural importance of dynamically activated descending inhibition from the nucleus reticularis gigantocellularis pars alpha.

We have recently demonstrated (J Physiol 506 (1998) 459) that the dynamic activation of descending inhibition of the nociceptive response of spinal multireceptive cells occurs in the nucleus reticularis gigantocellularis pars alpha (GiA). In the same paper we have shown that Lamina I dorsal horn cells are responsible for activating this inhibition via a pathway which runs in the contralateral dorsolateral funiculus. The effects of dynamically activating this system by noxious stimulation on behavioural responses to noxious stimuli have not been established. Here we demonstrate the effects of GiA on the behavioural response during application of standardized noxious stimuli. As this system is activated in response to noxious stimulation (J Physiol 506 (1998) 459), it is possible that chronic pain states may also activate GiA. We have therefore investigated this possibility in animals following partial sciatic nerve ligation (an animal model of chronic pain; Pain 43 (1990) 205). Male Wistar rats (280-310 g) were anaesthetized with halothane (0.5-2% in O(2)). Guide cannulae for microinjections were stereotaxically placed above GiA. In one group of animals the sciatic nerve was partially ligated. Animals were allowed to recover for 4-6 days. The responses of each animal during the formalin test (Pain 4 (1977) 161) and the tail flick test (Pain 12 (1982) 229) were recorded on different days. Microinjections (0.5 microl) of either gamma-aminobutyric acid (GABA, 200 mM), D-L homocysteic acid (DLH, 25 mM) or 0.9% saline (as control) into GiA were performed during these tests in a randomized, blind manner. In animals without sciatic nerve ligation, microinjection of GABA to GiA did not significantly affect the animal's response during the tail flick test. However microinjection of DLH significantly increased the latency of tail flick from 6.2 +/- 0.8 to 8.4 +/- 0.5 s for up to 15 min (n = 7, P < 0.01, Mann-Whitney U-test). Microinjection of GABA to GiA increased the behavioural response to formalin between 10 and 20 min post-injection, while microinjection of DLH reduced this response at all time points except 10 min post-injection (n = 8, P < 0.05, Mann-Whitney U-test). In animals with sciatic nerve ligation, microinjections (0.5 microl) of either GABA (200 mM), or saline (as control) into GiA contralateral to the partial sciatic ligation were performed during these tests in a randomized, blind manner. Partial sciatic ligation significantly reduced the behavioural response to contralaterally applied formalin from 15 min post-injection onwards, compared to controls without sciatic nerve ligation. Microinjection of GABA to GiA significantly increased the behavioural response to formalin from 20 to 50 min post-injection. The inactivation of GiA only causes behavioural effects in nociceptive tests of a long enough duration to activate the system (i.e. the formalin test but not the tail flick test). Chemical activation of the system affects both tests. These data strongly support the concept of an important analgesic system which is activated in response to noxious stimulation, and subsequently acts to reduce behavioural responses to noxious stimuli.

The antinociception evoked by anterior pretectal nucleus stimulation is partially dependent upon ventrolateral medullary neurones.

Electrical stimulation (35 microA rms/15 s) of the anterior pretectal nucleus (APtN) inhibits the spinal reflex of the tail-flick (TF) to noxious heat in unanaesthetised rats. APtN stimulation also reduces the nociceptive response of spinal dorsal horn neurones in halothane-anaesthetised rats. This study determined if the antinociceptive effects of APtN stimulation depended on neurones in the ventral medulla. Bilateral electrolytic lesions of the ventrolateral medulla, but not the nucleus raphe magnus, reduced by 70% the antinociceptive effect of APtN stimulation in the TF test. In rats anaesthetised with halothane, electrical stimulation of the APtN (single square wave 0.1 msec pulses, 2-20 microA, 1 Hz) excited cells in the ventrolateral medulla. These data suggest a connection between both areas. This connection is further confirmed by neuroanatomical tract tracing studies in which the retrograde dye Fast Blue was injected into the ventrolateral medulla. Fluorescent cell bodies were found in the APtN. We therefore conclude that the ventrolateral medulla is part of a descending antinociceptive pathway from the APtN.

5-Hydroxytryptamine and antinociception.

The considerable evidence supporting a role for 5-hydroxytryptamine (5-HT) in the modulation of nociceptive thresholds is reviewed. The postulate that an antinociceptive system of neurones projects from periaqueductal gray (PAG) to nucleus raphe magnus (NRM) and then to the dorsal horn, via cells containing 5-HT, has proved difficult to support experimentally. 5-Hydroxytryptamine, applied iontophoretically to dorsal horn neurones, does reduce the nociceptive responses of these neurones but it is not clear that activity in 5-HT cells of the raphe-spinal system is responsible for the descending inhibition of nociception. Although antagonists of 5-HT block some of the antinociceptive effects of both stimulation of the periaqueductal gray and systemically-applied morphine, they do not block the centrifugal inhibition of dorsal horn cells or the effects of iontophoretically applied 5-HT. Nor do they displace [3H]5-HT binding at low concentrations. Damage to, or selective depletion of 5-HT from the raphe-spinal 5-HT system has been reported not to alter nociceptive thresholds or the effects of stimulation of the periaqueductal gray. There is anatomical evidence for cells in the periaqueductal gray which contain 5-HT and project to the n. raphe magnus. Microinjected into the n. raphe magnus, 5-HT is antinociceptive in the tail-flick test and microinjection of an inhibitor of uptake of 5-HT or a 5-HT releasing agent, both cause antinociception. Furthermore, the effects of electrical stimulation of the periaqueductal gray are blocked by microinjection of a 5-HT antagonist into the n. raphe magnus.(ABSTRACT TRUNCATED AT 250 WORDS)

Brainstem mechanisms of antinociception. Effects of electrical stimulation and injection of morphine into the nucleus raphe magnus.

The microinjection of morphine into the nucleus raphe magnus (NRM) increased the tail-flick latency of rats but also increased the size of noxiously-evoked responses of dorsal horn neurones. Electrical stimulation of the raphe magnus reduced the response size of the same neurons to noxious stimulation. To control for the possibility that morphine had a membrane stabilising action upon cells in the raphe magnus, tetracaine was injected into the raphe magnus and found to reduce the size of noxiously-evoked responses of dorsal horn cells. Bilateral lesions of the dorsolateral funiculus reduced the effect on tail-flick latency of morphine injected into the raphe magnus, indicating that morphine was causing antinociception by an effect on descending systems. This effect of morphine was fundamentally different however from the effects of electrical stimulation. Antinociception may result from different mechanisms within the raphe magnus nucleus, affected by morphine and electrical stimulation.

A post-synaptic depressant modulatory action of 5-hydroxytryptamine on excitatory amino acid responses in rat entorhinal cortex in vitro.

The depressant action of 5-hydroxytryptamine (5-HT) in slices of entorhinal cortex of the rat has been examined. When single intracellular recordings of pyramidal cells in layers II/III of entorhinal cortex of the rat were made and drugs applied by iontophoresis, 5-HT evoked virtually no changes in passive membrane properties of the majority of cells studied. When short regular pulses of glutamate were applied to the neurones and 5-HT was ejected in addition, the depolarisations caused by glutamate were considerably reduced in amplitude. This attenuation persisted in medium containing cadmium chloride (200 microM) to block synaptic transmission. The magnitude of the response to 5-HT was dependent on the ejection current and this effect could not be mimicked by increasing ejections of Na+ or H+ ions. 5-Hydroxytryptamine had no apparent action on neuronal responses to iontophoretically ejected gamma-amino butyric acid (GABA). In later studies, the action of 5-HT was examined on epileptiform discharges, evoked in the presence of the GABA antagonist, bicuculline, in the same group of cells. Droplet application of 5-HT into the recording chamber, or perfusion of 10 microM 5-HT regularly attenuated the length of epileptiform bursts but, at this concentration, had no discernible effect on the resting membrane potential or membrane input resistance. The effect of 5-HT on the release of glutamate from slices of entorhinal cortex has also been examined using a fluorometric enzyme assay. Concentrations of 5-HT as large as 30 microM had no effect on the release of endogenous glutamate in these experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

The actions of the novel anti-aggressive drug eltoprazine on central neurones in the anaesthetised rat.

5-Hydroxytryptamine (5-HT) and the novel anti-aggressive drug eltoprazine (1-(2,3-dihydro-1,4-benzodioxin-5-yl) piperazine hydrochloride) were applied by microiontophoresis to spinal motorneurones and also to neurones in the brainstem which gave two distinctly different responses to 5-HT. In vitro microiontophoretic release studies showed that the electrophoretic mobility of eltoprazine and 5-HT were similar and that similar amounts of each drug would be applied by similar iontophoretic currents. Cells in the brainstem have been shown previously to be excited by 5-HT, acting at a 5-HT2 receptor. Eltoprazine only occasionally and weakly mimicked the excitatory effect of 5-HT on these cells. Although a potent antagonism of the 5-HT excitation by eltoprazine was observed, this was a non-selective effect, as responses to glutamate and D,L-homocysteic acid were also reduced. Cells in the lateral brainstem are depressed by 5-HT, acting on a receptor which has previously been shown to be of the 5-HT1-like group. At this receptor, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)-tetralin) and 5-carboxamidotryptamine, are potent agonists. Eltoprazine was a more potent depressant agonist than 5-HT on these brainstem neurones. The antagonist metergoline did not antagonise responses to either 5-HT or eltoprazine. It is suggested however that both drugs act at the same receptor to depress these cells because desensitizing the receptor by repeated, frequent applications of 5-HT abolished responses to 5-HT and eltoprazine, without altering responses to GABA.(ABSTRACT TRUNCATED AT 250 WORDS)

Direct projections from the anterior pretectal nucleus to the ventral medulla oblongata in rats.

The anterior pretectal nucleus has recently been implicated in the descending modulation of nociception. Electrical stimulation of the nucleus was found to reduce the nociceptive responses of deep dorsal horn neurons and to inhibit spinally integrated withdrawal reflexes. It is believed that at least part of the descending inhibitory effects of the anterior pretectal nucleus are mediated by reticulospinal cells of the ventrolateral medulla. The purpose of the present study was to trace the direct medullary projections of the anterior pretectal nucleus, to describe their topographical organization and to reveal the chemical nature of some of their putative target cells. The connections were studied using anterograde tract-tracing with Phaseolus vulgaris leucoagglutinin. Direct projections from the anterior pretectal nucleus to the ipsilateral rostral ventral medulla were found in all cases. A dense innervation of the dorsal inferior olive, the gigantocellular reticular nucleus pars ventralis and pars alpha and the ventral pontine reticular nucleus was found from all aspects of the anterior pretectal nucleus. Descending labelled terminals were also observed in the gigantocellular reticular nucleus proper and, laterally, in the lateral paragigantocellular nucleus and in the region of the A5 noradrenergic cell group. A relatively lower density of labelled terminals was noted in the medullary raphe nuclei and in the rostroventrolateral reticular nucleus. Following tract-tracer injections into five distinct subregions of the anterior pretectal nucleus, the topographical organization of the projection was examined and the relatively highest density and most widespread projection was found to originate from the caudoventral part of the anterior pretectal nucleus. A combined tract-tracing and immunolabelling study revealed that some of the descending, labelled terminals were in close proximity of tyrosine hydroxylase-immunoreactive dendrites in the C1 and A5 cell groups. Some labelled fibres were also noted among the serotonin-immunoreactive cells in the lateral extension of the B3 cell population. The existence of direct projections to the ventral medulla and pons correlates well with physiological data which showed that the descending, antinociceptive effects of the anterior pretectal nucleus are relayed via the rostral ventrolateral medulla. The data are also in keeping with pharmacological studies that suggested the role of catecholaminergic cells in the mediation of these descending effects. It is proposed that the rostral ventral medullary projections provide a path through which antinociceptive effects of the anterior pretectal nucleus are mediated to the spinal cord.

Afferent projections to the rostral anterior pretectal nucleus of the rat: a possible role in the processing of noxious stimuli.

The afferent inputs to the rostral pole of the anterior pretectal nucleus have been examined by utilizing the retrograde axonal transport of a fluorescent dye, Fast Blue. After unilateral injection of the dye into the rostral anterior prectectal nucleus, large numbers of labelled neuronal somata were found in the somatosensory cortex, the ventrolateral geniculate nucleus, the zona incerta, the superior colliculus, the deep mesencephalic nuclei, the pedunculopontine tegmental nucleus and the medial vestibular nucleus. In addition, the contralateral parabigeminal nucleus provided a major input to the rostral part of the anterior pretectal nucleus. Smaller and sparser collections of stained cell bodies could be found in the ventromedial hypothalamus, the posterior pretectal nucleus, the nucleus of the posterior commissure, the peripeduncular nucleus, the periaqueductal central gray, the contralateral anterior pretectal nucleus, and the locus coeruleus. Many of the inputs originated in areas associated with nociceptive pathways. The regional distribution of neurons projecting to the rostral pole of the anterior pretectal nucleus differs substantially from that of the cells innervating the anterior pretectal nucleus proper, i.e. its more caudal parts. It is concluded from this that the rostral pole constitutes a separate nucleus, anatomically distinct from the rest of the anterior pretectal nucleus and other cell groups in the pretectal complex. The demonstration that many of the afferents to the rostral anterior pretectal nucleus arise in regions involved in nociception supports recent electrophysiological and behavioural evidence that this brain area plays a role in the processing of noxious stimuli, rather than as a component in the pretectal control of visual system reflexes.

Monoclonal antibodies recognize localized antigens in the eye and central nervous system of the marine snail Bulla gouldiana.

The eyes of the marine snail Bulla gouldiana act as circadian pacemakers. The eyes exhibit a circadian variation in spontaneous optic nerve compound action potential frequency in constant darkness, and are involved in controlling circadian rhythms in behavioral activity expressed by the animal. To initiate an investigation of the molecular aspects of circadian rhythmicity in the Bulla eye and to identify specific molecular markers in the nervous system, we raised monoclonal antibodies (MAb) to the eye and screened them for specific patterns of staining in the eye and brain. Several MAb recognize antigens specific to groups of neurons in the brain, whereas others stain antigens found only in the eye. In addition, some antigens are shared by the eye and the brain. The antigens described here include molecules that mark the lens, retina, neural pathways between the eye and the brain, specific groups of neurons within the central ganglia, and an antigen that is shared by basal retinal neurons (putative ocular circadian pacemaker cells) and glia. These molecular markers may have utility in identifying functionally related groups of neurons, elucidating molecular specializations of the retina, and highlighting pathways used in transmission of information between the retina and the brain.