Tachykinin NK(3)receptor involvement in anxiety

This study investigates the effects of intracerebroventricular injection of selective agonists and antagonists of tachykinin NK(3)receptor on performance of mice in the elevated plus-maze test. Mice were treated with either vehicle or 1, 10, 100 or 500 pmol of neurokinin B or senktide ([succinil-Asp(6), MePhe(8)]substance P(6-11), a natural and synthetic selective NK(3)receptor agonists, respectively. Other mice received similar doses of [Trp(7)beta-Ala(8)]NKA(4-10)or SR 142801 ((S)-N-(1-(3-(1-benzoyl-3-(3, 4-dichlorophenyl)-piperidin-3-yl)propyl)-4-phenyl-piperidin- 4-yl)-N-m ethylacetamide) tachykinin NK(3)receptor selective peptide and non-peptide antagonists, respectively. Senktide significantly increased the frequency of entries and the time spent in the open arms, which is compatible with an anxiolytic action. Neurokinin B treatment did not alter the plus-maze parameters in a significant way. Conversely, the NK(3)peptide antagonist [Trp(7)beta-Ala(8)]NKA(4-10), but not SR142801 non-peptide antagonist, showed a reverse effect, i.e. an anxiogenic profile of action, reducing the frequency and the time spent in the open arms. Co-injection of either senktide plus [Trp(7)beta-Ala(8)]NKA((4-10)), or senktide plus SR 142801, blocked the effects promoted by senktide, indicating that centrally-administered NK(3)receptor agonists and antagonists can modulate experimental anxiety.     

Adenosine modulates synaptic plasticity in hippocampal slices from aged rats

Adenosine is known to modulate synaptic plasticity in the hippocampus of young animals through activation of adenosine A1 receptors. The objective of the present study is to investigate whether the modulatory role of adenosine on phenomena of synaptic plasticity is maintained or modified in the hippocampus of aged animals. We compared the effects of the selective adenosine A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 50 nM), on paired-pulse facilitation (PPF), long-term depression (LTD), long-term potentiation (LTP) and depotentiation elicited in hippocampal slices taken from young adult (5-6 weeks) and old (2 years old) male Wistar rats. DPCPX attenuated PPF both in young (1.64 +/- 0.05 vs. 1.76 +/- 0.05%, n = 6) and in old rats (1.33 +/- 0.05 vs. 1.55 +/- 0.1%, n = 6). LTD was only observed in the presence of DPCPX in both young (21.3 +/- 0.6%, n = 4) and old rats (14.4 +/- 0.9%, n = 6). LTP induced by high-frequency stimulation (HFS) was not significantly different in young and old animals, in the presence or in the absence of DPCPX. A larger depotentiation was observed in the presence of DPCPX in young rats (27.6 +/- 4.4% vs. 16.8 +/- 4.7%, n = 7) as well as in old rats (41.3 +/- 5.1% vs. 16.1 +/- 2.7%, n = 6). LTP induced by theta-burst stimulation was observed only in the presence of DPCPX (53.9 +/- 4.9%, n = 5) in young rats, but could be obtained either in the control solution (81.8 +/- 17.9%, n = 7) or in the presence of DPCPX (98.5 +/- 24.2%, n = 7) in old rats. The modulatory role of endogenous adenosine on synaptic plasticity is generally maintained in aged animals. Drugs interfering with adenosine A1 receptor effects could then be used in old animals to modify synaptic plasticity with relevant behavioural consequences.     

Slow sharp waves.

Slow sharp waves (SSHW) are of longer duration (around 200 msec and longer) than typical sharp wave discharges (70 to 200 msec). This pattern is not merely of academic interest, as the electroclinical correlation showed that SSHW were found in 23 patients, mostly above age 50 years, with serious illnesses of various etiologies. Epileptic seizures occurred in a minority of the cases. The electrophysiological basis remains unclear and there is no answer to the question, "what causes the relatively long duration of these discharges?"     

Bilateral Pseudomonas corneal ulcer in a disposable contact lens wearer.

PURPOSE: To describe a case of bilateral corneal ulcers caused by Pseudomonas in a disposable soft contact lens wearer. This case study discusses the role of patient examination, contact lens care instruction, and adequate patient supervision in reducing the risk of serious potential complications. METHODS AND RESULTS: A 17 year old student who had been using disposable soft contact lenses on an extended wear basis for 6 months presented complaining of pain in the left eye. When he was examined, a corneal ulcer with surrounding infiltrate was observed in the superior middle periphery of the left eye. Samples were collected for culture, and treatment with fortified cefalotin and gentamicin was started. After 8 hours the patient returned, now complaining of pain in the right eye. Examination of the right eye revealed a diffused keratitis with a mucopurulent discharge. A culture was taken, and the same treatment was instituted. The laboratory tests revealed Pseudomonas in both eyes. The bilateral corneal ulcers responded to therapy after 1 week of treatment. CONCLUSIONS: We discuss the factors involved in the occurrence of infectious keratitis in contact lens wearers, and stress that even disposable contact lens wear can be associated with serious complications. This case also highlights extended wear as one of the main risk factors for complications in disposable soft contact lens wear.     

Kainate receptors coupled to G(i)/G(o) proteins in the rat hippocampus.

Kainate receptors are a subtype of ionotropic glutamate receptors, permeable to cations and thus expected to have an excitatory depolarizing action on neurons. However, kainate receptor activation inhibits gamma-aminobutyric acid release in the hippocampus through activation of protein kinase C in a pertussis toxin-dependent manner, suggesting a coupling of kainate receptors to G proteins. Thus, we directly investigated the G protein coupling of kainate receptors in the rat hippocampus by using a selective kainate receptor agonist, [(3)H](2S,4R)-4-methylglutamate ([(3)H]MGA). [(3)H]MGA bound to a single site to hippocampal membranes with a K(D) value of 32 nM and a B(max) value of 1024 fmol/mg protein. This binding likely represents kainate receptors because it was displaced by domoate (K(i) = 4 nM), kainate (K(i) = 11 nM), and 6-cyano-7-nitroquinoxaline-2,3-dione (K(i) = 1.4 microM), but not by alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (K(i) > 10 microM), (RS)-alpha-methyl-4-phosphonophenylglycine (K(i) > 10 microM), or (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (K(i) > 10 microM). Guanylylimidodiphosphate (30 microM), which uncouples all G protein-coupled receptors, shifted to the right the saturation curve of [(3)H]MGA (K(D) = 133 nM). This effect was mimicked by pretreatment of hippocampal membranes with modifiers of G(i)/G(o) proteins [30 microM N-ethylmaleimide (K(D) = 98 nM) or 25 microgram/ml pertussis toxin (K(D) = 95 nM)] but not by a modifier of G(s) proteins [50 microgram/ml cholera toxin (K(D) = 32 nM)]. Treatment of solubilized hippocampal membranes with pertussis toxin (25 microgram/ml) decreased [(3)H]MGA affinity (K(D) = 105-113 nM), which was recovered by reconstitution of these pretreated solubilized hippocampal membranes with G(i)/G(o) proteins (K(D) = 41-76 nM). These results indicate that hippocampal kainate receptors are coupled to G(i)/G(o) proteins.     

Reactions of 'bay-region' and non-'bay-region' diol-epoxides of benz(a)anthracene with DNA: evidence indicating that the major products are hydrocarbon-N2-guanine adducts

The rates of reaction and the products formed when two vicinaldiol-epoxides derived from benz(a)an-thracene, anti-BA-3, 4-dioI1, 2-oxide (t-3, r-4-dihydroxy-t-1, 2-oxy-l, 2, 3, 4-tetrahydrobenz(a)anthracene)^* and anti-BA-8, 9-diol 10, 11-oxide (r-8, t-9-dihydroxy-t-10,ll-oxy-8, 9, 10, ll-tetrahydro-benz(a)anthracene) reacted withDNA were studied in vitro and the results were compared withthose obtained in similar experiments using anti-BP-7, 8-diol9, 10-oxide (r-7, t-8-dihydroxy-t-9, 10-oxy-7, 8, 9, 10-tetrahydrobenzo(a)pyrene).The reactivities appeared to decrease in the order anti-BP-7,8-diol 9, 10-oxide > anti-BA-3, 4-diol 1, 2-oxide anti-BA-8,9-diol 10, 11-oxide. The diol-epoxides reacted to a similarextent with single- and with double-stranded DNA but reactionswith dGMP, at equivalent concentrations, were much slower thanwith DNA. With the diol-epoxides of benz(a)anthracene, two principaladducts were present in DNA hydrolysates and evidence was obtained,based on pK determinations before and after nitrous acid treatment,consistent with their being N²-guanine derivatives, analogousto the known DNA-reaction products of benzo(a)-pyrene 7, 8-diol9, 10-oxide.     

Multiple myeloma in an adolescent

The radiographic findings of a 15-year-old Brazilian male with diagnosis of multiple myeloma are described. He presented with claudication and recent onset of tender painful swelling of the right mid leg. Radiographs showed wide spread soap bubble lesions of the skull, long bones, spine, pelvis, ribs, shoulders, and clavicles. The diagnosis was confirmed by the presence of a plasmacytoma on tissue biopsy (femur), serum IgG gammopathy and Bence-Jones proteinuria.Supported by grants (CA-20180 and CA-21765) from the National Cancer Institute and the American Lebanese Syrian Associated Charities (ALSAC)     

Magnetic resonance imaging in the evaluation of patients with aseptic meningoencephalitis and connective tissue disorders

OBJECTIVE: To describe the role of magnetic resonance imaging (MRI) in the evaluation of patients with chronic and recurrent aseptic meningitis. METHOD: A retrospective study of five patients with aseptic meningoencefalitis diagnosed by clinical and CSF findings. CT scans showed without no relevant findings. RESULTS: MRI showed small multifocal lesions hyperintense on T2 weighted images and FLAIR, with mild or no gadolinium enhancement, mainly in periventricular and subcortical regions. Meningoencephalitis preceded the diagnosis of the underlying disease in four patients (Beh?et's disease or systemic lupus erythematosus). After the introduction of adequate treatment for the rheumatic disease, they did not present further symptoms of aseptic meningoencephalitis. CONCLUSION: Aseptic meningoencephalitis can be an early presentation of an autoimmune disease. It is important to emphasize the role of MRI in the diagnosis and follow-up of these patients.     

Inhibition of hemorrhagic and edematogenic activities of snake venoms by a broad-spectrum protease inhibitor, murinoglobulin; the effect on venoms from five different genera in Viperidae family.

In order to obtain basic data on the effect of broad-spectrum protease inhibitor against local symptoms of Viperidae snake envenomation, inhibitory capacity of rat murinoglobulin on local hemorrhagic and edematogenic activities of venoms from Crotalus atrox, Bothrops jararaca, Lachesis muta muta, Trimeresurus flavoviridis and Echis carinatus sochureki were examined. Murinoglobulin, pre-incubated with the crude venoms at 37 degrees C for 15 min, inhibited hemorrhagic activity of all five venoms to various extents. The activity of C. atrox was almost completely inhibited at the murinoglobulin/venom ratio (w/w) of 20. The activity of B. jararaca, Lachesis muta muta and T. flavoviridis venoms was considerably inhibited at the ratio of 20 (77.2, 80.0 and 86.2% inhibition, respectively), however some of the activity still remained even at the ratio of 40 (84.2, 79.8 and 86.2% inhibition, respectively). Among the five venoms, E. c. sochureki venom is quite resistant to murinoglobulin treatment and statistically significant inhibition was only found at the ratio of 40 (64.1% inhibition). Fibrinolytic and gelatinase activities were more susceptible to murinoglobulin inhibition. The treatment at the ratios of 10 and 20 almost completely inhibited respectively the fibrinolytic and the gelatinase activities of all the venoms. Murinoglobulin treatment also significantly inhibited the edematogenic activity of L. muta muta, T. flavoviridis and Echis carinatus sochureki. The treatment of murinoglobulin at the ratio of 40 considerably suppressed the swelling up to 60 min after subcutaneous injection of L. muta muta and E. c. sochureki venoms, and up to 30 min after T. flavoviridis venom injection. Murinoglobulin is a potent inhibitor against local effects of multiple snake venoms in Viperidae family.     

Induction of partial protection in mice after oral administration of Lactococcus lactis producing Brucella abortus L7/L12 antigen.

The Brucella abortus ribosomal protein L7/L12 is an immunodominant antigen and an interesting candidate for the development of oral live vaccines against brucellosis. Here, a recombinant Lactococcus lactis strain producing L7/L12 under the control of nisin inducible promoter was orally administered to BALB/c mice. Significant levels of anti-L7/L12 specific IgA detected in feces revealed an induced local humoral immune response. However, serum analysis did not reveal any anti-L7/L12 antibodies suggesting the absence of a systemic response. Nevertheless, the vaccinated mice showed a partial protective immunity against B. abortus virulent strain (S2308) challenged by intraperitoneal inoculation.