Marcadores microssatélites relacionados com a resistência à vassoura-de-bruxa do cacaueiro Microsatellite markers related to resistance of cocoa tree against witches'-broom

Os objetivos deste trabalho foram caracterizar a resistência à vassoura-de-bruxa de plantas de cacau originadas do cruzamento entre TSH 1188 e CCN 51 (população segregante), por meio de dois métodos de inoculação em condições de campo, e identificar marcadores microssatélites específicos para grupos de plantas resistentes e suscetíveis. As plantas-controle avaliadas pelos métodos de inoculação natural e inoculação artificial em campo produziram os mesmos padrões de sintomas. As plantas da população segregante também coincidiram os padrões de sintomas em 90%, por esses dois métodos. O método de inoculação artificial em campo permite detectar falso-resistentes. Dos 18 pares de primers microssatélites amplificados, 15 foram polimórficos entre os genitores, e seis entre os grupos de plantas segregantes contrastantes quanto à resistência à vassoura-de-bruxa. Foram confirmadas três marcas previamente associadas a QTL (locos para características quantitativas) relacionados com a resistência à vassoura-de-bruxa, comuns a outras populações. Também foram identificados três novos QTL para esta característica, típicos desta população, o que comprova sua utilidade para o melhoramento genético do cacaueiro.<br>The objectives of this work were to evaluate cocoa tree resistance against witches'-broom, in plants originated from the crossing between TSH 1188 and CCN 51 (segregating population), by means of two methods of inoculation in field conditions, and to identify microsatellite markers specific for resistant and susceptible plants. The control plants bore identical symptoms as the plants of the segregating population in 90% of the cases under the two methods. The method of artificial inoculation in the field allows the detection of false resistance to the disease. Of the 18 pairs of microsatellite primers amplified, 15 were polymorphic between genitors and six were polymorphic between the two groups of plants evaluated for resistance to witches'-broom. Three previously characterized markers were confirmed as associated to QTL (quantitative trait loci) related to resistance to the witches'-broom, which is common in other populations. Three new QTL for this characteristic, typical of this population, were also identified, which proves the utility of this population for cocoa breeding

Brazilian Guidelines For The Diagnosis Of Narcolepsy [diretrizes Brasileiras Para O Diagnóstico Da Narcolepsia]

This manuscript contains the conclusion of the consensus meeting on the diagnosis of narcolepsy based on the review of Medline publications between 1980-2010. Narcolepsy is a chronic disorder with age at onset between the first and second decade of life. Essential narcolepsy symptoms are cataplexy and excessive sleepiness. Cataplexy is defined as sudden, recurrent and reversible attacks of muscle weakness triggered by emotions. Accessory narcolepsy symptoms are hypnagogic hallucinations, sleep paralysis and nocturnal fragmented sleep. The clinical diagnosis according to the International Classification of Sleep Disorders is the presence of excessive sleepiness and cataplexy. A full in-lab polysomnography followed by a multiple sleep latency test is recommended for the confirmation of the diagnosis and co-morbidities. The presence of two sleep-onset REM period naps in the multiple sleep latency test is diagnostic for cataplexy-free narcolepsy. A positive HLA-DQB1*0602 with lower than 110pg/mL level of hypocretin-1 in the cerebrospinal fluid is required for the final diagnosis of cataplexy- and sleep-onset REM period-free narcolepsy.323294304(2005) International Classification of Sleep Disorders, Second Edition: Diagnostic and Coding Manual, , American Academy of Sleep Medicine. Westchester, IL: American Academy of Sleep MedicineLongstreth Jr., W.T., Ton, T.G., Koepsell, T., Gersuk, V.H., Hendrickson, A., Velde, S., Prevalence of narcolepsy in King County, Washington, USA (2009) Sleep Med, 10 (4), pp. 422-426Longstreth Jr., W.T., Koepsell, T.D., Ton, T.G., Hendrickson, A.F., Van Belle, G., The epidemiology of narcolepsy (2007) Sleep, 30 (1), pp. 13-26Silber, M.H., Krahn, L.E., Olson, E.J., Pankratz, V.S., The epidemiology of narcolepsy in Olmsted County, Minnesota: A population-based study (2002) Sleep, 25 (2), pp. 197-202Hublin, C., Kaprio, J., Partinen, M., Koskenvuo, M., Heikkila, K., Koskimies, S., Guillemmault, C., The prevalence of narcolepsy: An epidemiological study of the Finnish twin cohort (1994) Annals of Neurology, 35 (6), pp. 709-716. , DOI 10.1002/ana.410350612Wing, Y.K., Li, R.H., Lam, C.W., Ho, C.K., Fong, S.Y., Leung, T., The prevalence of narcolepsy among Chinese in Hong Kong (2002) Ann Neurol, 51 (5), pp. 578-584Mignot, E., Genetic and familial aspects of narcolepsy (1998) Neurology, 50 (2 SUPPL. 1), pp. S16-22Mignot, E., Lin, L., Rogers, W., Honda, Y., Qiu, X., Lin, X., Okun, M., Risch, N., Complex HLA-DR and -DQ interactions confer risk of narcolepsycataplexy in three ethnic groups (2001) Am J Hum Genet, 68 (3), pp. 686-699Pelin, Z., Guilleminault, C., Risch, N., Grumet, F.C., Mignot, E., HLA-DQB1*0602 homozygosity increases relative risk for narcolepsy but not disease severity in two ethnic groups (1998) Tissue Antigens, 51 (1), pp. 96-100. , US Modafinil in Narcolepsy Multicenter Study GroupMignot, E., Kimura, A., Latlermann, A., Lin, X., Yasunaga, S., Mueller-Eckhardt, G., Rattazzi, C., Underbill, P., Extensive HLA class II studies in 58 non-DRB 1*15 (DR2) narcoleptic patients with cataplexy (1997) Tissue Antigens, 49 (4), pp. 329-341Ellis, M.C., Hetisimer, A.H., Ruddy, D.A., Hansen, S.L., Kronmal, G.S., McClelland, E., Quintana, L., Mignot, E., HLA class II haplotype and sequence analysis support a role for DQ in narcolepsy (1997) Immunogenetics, 46 (5), pp. 410-417Mignot, E., Lin, X., Arrigoni, J., Macaubas, C., Olive, F., Hallmayer, J., Underhill, P., Grumet, F.C., DQB1*0602 and DQA1*0102 (DQ1) are better markers than DR2 for narcolepsy in Caucasian and black Americans (1994) Sleep, 17 (8 SUPPL.), pp. S60-7Mignot, E., Hayduk, R., Black, J., Grumet, F.C., Guilleminault, C., HLA DQB1*0602 is associated with cataplexy in 509 narcoleptic patients (1997) Sleep, 20 (11), pp. 1012-1020Morgun, A., Gonçalves-Primo, A., Shulzhenko, N., Rampim, G.F., Mine, K.L., Gerbase-DeLima, M., HLA-DQB1 and -DRB1 Alleles, Cytokine Polymorphismis and KIR Gene Frequencies in a Population (Caucasian) from South East Brazil (2004) Hum Immunol, 65 (9), pp. 879-882Temin, J., Marques, G.D., Morgun, A., Shulzhenko, N., Rampim, G.F., Gerbase-de Lima, M., HLA-DQB1 and -DRB1 Alleles and Cytokine Polymorphismis in a Mulatto population from South East Brazil (2004) Hum Immunol, 65 (9), pp. 882-886Miyagawa, T., Honda, M., Kawashima, M., Shimada, M., Tanaka, S., Honda, Y., Tokunaga, K., Polymorphism located in TCRA locus confers susceptibility to essential hypersomnia with HLA-DRB1*1501-DQB1*0602 haplotype (2010) J Hum Genet, 55 (1), pp. 63-65Hallmayer, J., Faraco, J., Lin, L., Hesselson, S., Winkelmann, J., Kawashima, M., Mayer, G., Mignot, E., Narcolepsy is strongly associated with the T-cell receptor alpha locus (2009) Nat Genet, 41 (6), pp. 708-711Dauvilliers, Y., Neidhart, E., Lecendreux, M., Billiard, M., Tafti, M., MAO-A and COMT polymorphisms and gene effects in narcolepsy (2001) Molecular Psychiatry, 6 (4), pp. 367-372. , DOI 10.1038/sj.mp.4000911Dauvilliers, Y., Neidhart, E., Billiard, M., Tafti, M., Sexual dimorphism of the catechol-O-methyltransferase gene in narcolepsy is associated with response to modafinil (2002) Pharmacogenomics Journal, 2 (1), pp. 65-68. , DOI 10.1038/sj.tpj.6500088Dauvilliers, Y., Arnulf, I., Narcolepsie avec cataplexie (2008) Revue Neurologique, 164 (8-9), pp. 634-645Dauvilliers, Y., Arnulf, I., Mignot, E., Narcolepy with cataplexy (2007) Lancet, 369 (9560), pp. 499-511Nishino, S., Clinical and neurobiological aspects of narcolepsy (2007) Sleep Med, 8 (4), pp. 373-399Nishino, S., Narcolepsy (2006) Sleep Med Clin, 1, pp. 47-61Dauvilliers, Y., Billiard, M., Montplaisir, J., Clinical aspects and pathophysiology of narcolepsy (2003) Clin Neurophysiol, 114 (11), pp. 2000-2017Thannickal, T.C., Nienhuis, R., Siegel, J.M., Localized loss of hypocretin (orexin) cells in narcolepsy without cataplexy (2009) Sleep, 32 (8), pp. 993-998Overeem, S., Black III, J.L., Lammers, G.J., Narcolepsy: Immunological aspects (2008) Sleep Med Rev, 12 (2), pp. 95-107Boehmer, L.N., Wu, M.-F., John, J., Siegel, J.M., Treatment with immunosuppressive and anti-inflammatory agents delays onset of canine genetic narcolepsy and reduces symptom severity (2004) Experimental Neurology, 188 (2), pp. 292-299. , DOI 10.1016/j.expneurol.2004.04.006, PII S0014488604001396Vignatelli, L., D'Alessandro, R., Mosconi, P., Ferini-Strambi, L., Guidolin, L., De Vincentiis, A., Plazzi, G., Health-related quality of life in Italian patients with narcolepsy: The SF-36 health survey (2004) Sleep Med, 5 (5), pp. 467-475. , GINSEN (Gruppo Italiano Narcolessia-Studio Epidemiologico Nazionale)Rieger, M., Mayer, G., Gauggel, S., Attention deficits in patients with narcolepsy (2003) Sleep, 26 (1), pp. 36-43Bayon, V., Damien Léger, D., Philip, P., Socio-professional handicap and accidental risk in patients with hypersomnias of central origin (2009) Sleep Med, 13 (6), pp. 421-426Aldrich, M.S., Automobile accidents in patient with sleep disorders (1989) Sleep, 12 (6), pp. 487-494Fortuyn, H.A., Lappenschaar, M.A., Furer, J.W., Hodiamont, P.P., Rijnders, C.A., Renier, W.O., Buitelaar, J.K., Overeem, S., Anxiety and mood disorders in narcolepsy: A case-control study (2010) Gen Hosp Psychiatry, 32 (1), pp. 49-56Bonakis, A., Howard, R.S., Williams, A., Bonakis, A., Howard, R.S., Williams, A., Narcolepsy presenting as REM sleep behaviour disorder (2008) Clinical Neurol Neurosurg, 110 (5), pp. 518-520Dauvilliers, Y., Rompre, S., Gagnon, J.-F., Vendette, M., Petit, D., Montplaisir, J., REM sleep characteristics in narcolepsy and REM sleep behavior disorder (2007) Sleep, 30 (7), pp. 844-849Mattarozzi, K., Bellucci, C., Campi, C., Cipolli, C., Ferri, R., Franceschini, C., Mazzetti, M., Plazzi, G., Clinical, behavioural and polysomnographic correlates of cataplexy in patients with narcolepsy/cataplexy (2008) Sleep Med, 9 (4), pp. 425-433Nevsimalova, S., Prihodova, I., Kemlink, D., Linm, L., Mignot, E., REM behavior disorder (RBD) can be one of the first symptoms of childhood narcolepsy (2007) Sleep Med, 8 (7-8), pp. 784-786Nightingale, S., Orgill, J.C., Ebrahim, I.O., De Lacy, S.F., Agrawal, S., Williams, A.J., The association between narcolepsy and REM behavior disorder (RBD) (2005) Sleep Med, 6 (3), pp. 253-258Fortuyn, H.A., Swinkels, S., Buitelaar, J., Renier, W.O., Furer, J.W., Rijnders, C.A., Hodiamont, P.P., Overeem, S., High prevalence of eating disorders in narcolepsy with cataplexy: A case-control study (2008) Sleep, 31 (3), pp. 335-341Dahmen, N., Bierbrauer, J., Kasten, M., Increased prevalence of obesity in narcoleptic patients and relatives (2001) Eur Arch Psychiatry Clin Neurosci, 251 (2), pp. 85-89Chabas, D., Foulon, C., Gonzalez, J., Nasr, M., Lyon-Caen, O., Willer, J.C., Derenne, J.P., Arnulf, I., Eating disorder and metabolism in narcoleptic patients (2007) Sleep, 30 (10), pp. 1267-1273Kotagal, S., Krahn, L.E., Slocumb, N., A putative link between childhood narcolepsy and obesity (2004) Sleep Med, 5 (2), pp. 147-150Sansa, G., Iranzo, A., Santamaria, J., Obstructive sleep apnea in narcolepsy (2010) J Sleep Med, 11 (1), pp. 93-95Dahmen, N., Kasten, M., Wieczorek, S., Gencik, M., Epplen, J.T., Ullrich B, B., Increased frequency of migraine in narcoleptic patients: A confirmatory study (2003) Cephalalgia, 23 (1), pp. 14-19Dahmen, N., Querings, K., Grun, B., Bierbrauer, J., Increased frequency of migraine in narcoleptic patients (1999) Neurology, 52 (6), pp. 1291-1293Nishino, S., Kanbayashi, T., Symptomatic narcolepsy, cataplexy and hypersomnia, and their implications in the hypothalamic hypocretin/orexin system (2005) Sleep Med Rev, 9 (4), pp. 269-310Billiard, M., Diagnosis of narcolepsy and idiopathic hypersomnia. An update based on the International Classification of Sleep Disorders (2007) Sleep Med Rev, 11 (5), pp. 377-388Sasai, T., Inoue, Y., Komada, Y., Sugiura, T., Matsushima, E., Comparison of clinical characteristics among narcolepsy with and without cataplexy and idiopathic hypersomnia without long sleep time, focusing on HLA-DRB1*1501/DQB1*0602 finding (2009) Sleep Med, 10 (9), pp. 961-966Arnulf, I., Zeitzer, J.M., File, J., Farber, N., Mignot, E., Kleine-Levin syndrome: A systematic review of 186 cases in the literature (2005) Brain, 128 (PART 12), pp. 2763-2776Doose, H., Myoclonic-astatic epilepsy in early childhood (1992) Epileptic Syndromes in Infancy, Childhood and Adolescence, pp. 103-114. , Roger J, Bureau M, Dravet C, editors. 2 ed. 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Brazilian Guidelines For The Treatment Of Narcolepsy [diretrizes Brasileiras Para O Tratamento Da Narcolepsia]

This manuscript contains the conclusion of the consensus meeting of the Brazilian Sleep Association with Brazilian sleep specialists on the treatment of narcolepsy based on the review of medical literature from 1980 to 2010. The manuscript objectives were to reinforce the use of agents evaluated in randomized placebo-controlled trials and to issue consensus opinions on the use of other available medications as well as to inform about safety and adverse effects of these medications. Management of narcolepsy relies on several classes of drugs, namely, stimulants for excessive sleepiness, antidepressants for cataplexy and hypnotics for disturbed nocturnal sleep. Behavioral measures are likewise valuable and universally recommended. All therapeutic trials were analyzed according to their class of evidence. Recommendations concerning the treatment of each single symptom of narcolepsy as well as general recommendations were made. Modafinil is the first-line pharmacological treatment of excessive sleepiness. Second-line choices for the treatment of excessive sleepiness are slow-release metylphenidate followed by mazindol. The first-line treatments of cataplexy are the antidepressants, reboxetine, clomipramine, venlafaxine, desvenlafaxine or high doses of selective serotonin reuptake inibitors antidepressants. As for disturbed nocturnal sleep the best option is still hypnotics. 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