pseudomonas-aeruginosa-induced-lung-injury-model

<em>Pseudomonas aeruginosa</em> Induced Lung Injury Model

In order to study human acute lung injury and pneumonia, it is important to develop animal models to mimic various pathological features of this disease. ...

University of Illinois at Chicago

The nasopharyngeal bacterial flora of healthy rhesus macaques was surveyed for the presence of Neisseria and Haemophilus species, as well as Moraxella catarrhalis. M. catarrhalis was found both in healthy rhesus macaques and in possibly immunocompromised rhesus macaques. Several Haemophilus spp. that are part of the normal nasopharyngeal bacterial flora of humans were found in many animals; these Haemophilus species included H. parahaemolyticus, H. segnis, and H. parainfluenzae. While Haemophilus influenzae was not identified, it is possible that the identification of H. influenzae types may have been thwarted by the growth of less fastidious species. A number of animals harbored Neisseria spp. such as N. sicca. However, Neisseria meningitidis was not found. In summary, it appears as though the rhesus macaque may be used as a model for M. catarrhalis infections. Moreover, in view of the susceptibility of macaques to organisms of the Haemophilus and Neisseria genera, it is possible that these animals may also accurately model nontypeable H. influenzae and N. meningitidis infections.

Assessment of the nasopharyngeal bacterial flora of rhesus macaques: moraxella, Neisseria, haemophilus, and other genera.

Alcohol and human immunodeficiency virus (HIV) produce similar neuropathological profiles, including loss of neurons in the frontal cortex. Additionally, HIV-positive patients with a history of alcohol abuse have greater neurologic deficits, and chronic alcohol abuse produces electrophysiological deficits earlier in the HIV disease process. Few studies, preclinical or clinical, have examined whether alcohol administration exacerbates the neuropsychological deficits in subjects with lentiviruses such as HIV.

Alcohol unmasks simian immunodeficiency virus-induced cognitive impairments in rhesus monkeys.

Ischemic preconditioning (PC) is a phenomenon whereby a brief exposure to ischemia renders a tissue more tolerant to a subsequent sustained ischemic insult. Animals of the Spontaneously Hypertensive (SHR) and the Spontaneously Hypertensive Stroke-Prone (SHR-SP) rat strains produce cerebral infarcts that are larger and more reproducible in size than infarcts of normotensive rats. This study compared the effects of PC in SHR and SHR-SP rats, under the hypothesis that PC may not be as effective in the SHR-SP, a strain genetically predisposed to stroke. There were two groups per strain, with between eight and ten animals each. The Precondition group (PC) had a 10 min occlusion of the middle cerebral artery on day -1. On the same day the Sham group (Sham) received sham surgery. On day 0, both groups underwent permanent occlusion of the middle cerebral artery. The ischemic lesion was measured on day 1 using T(2)-weighted magnetic resonance imaging. Percent hemispheric infarct was significantly reduced in SHR PC vs. SHR Sham, SHR-SP PC vs. SHR-SP Sham, and SHR PC vs. SHR-SP PC. Thus, rats of the SHR-SP strain respond to PC less markedly than SHR animals. Both models may now be used to elucidate the mechanisms underlying PC.

Strain-dependent response to cerebral ischemic preconditioning: differences between spontaneously hypertensive and stroke prone spontaneously hypertensive rats.

Malaria transmission-blocking vaccination can effectively reduce and/or eliminate transmission of parasites from the human host to the mosquito vector. The immunity achieved by inducing an antibody response to surface antigens of male and female gametes and parasite stages in the mosquito. Our laboratory has developed DNA vaccine constructs, based on Pfs25 (a Plasmodium falciparum surface protein of 25 kDa), that induce a transmission-blocking immune response in mice (C. A. Lobo, R. Dhar, and N. Kumar, Infect. Immun. 67:1688-1693, 1999). To evaluate the safety, immunogenicity, and efficacy of the Pfs25 DNA vaccine in nonhuman primates, we immunized rhesus macaques (Macaca mulatta) with a DNA vaccine plasmid encoding Pfs25 or a Pfg27-Pfs25 hybrid or with the plasmid (empty plasmid) alone. Immunization with four doses of these DNA vaccine constructs elicited antibody titers that were high but nonetheless unable to reduce the parasite's infectivity in membrane feeding assays. Further boosting of the antibody response with recombinant Pfs25 formulated in Montanide ISA-720 increased antibody titers (30-fold) and significantly blocked transmission of P. falciparum gametocytes to Anopheles mosquitoes (approximately 90% reduction in oocyst numbers in the midgut). Our data show that a DNA prime-protein boost regimen holds promise for achieving transmission-blocking immunity in areas where malaria is endemic and could be effective in eradicating malaria in isolated areas where the level of malaria endemicity is low.

Induction of Plasmodium falciparum transmission-blocking antibodies in nonhuman primates by a combination of DNA and protein immunizations.

The principal vector of Borrelia burgdorferi, the Lyme borreliosis spirochete, in the Northeast and Midwestern regions of the United States is the blacklegged tick Ixodes scapularis. Because of a favorable environment, I. scapularis is also plentiful in the South; however, a correlation with Lyme borreliosis cases does not exist in this region of the United States. Concern existed that something intrinsic to ticks found in Louisiana could mitigate their ability to transmit B. burgdorferi. Therefore, we set out to assess the ability of I. scapularis ticks from Louisiana to become infected with and transmit B. burgdorferi using mice as hosts. In the laboratory, mating adult female ticks collected in southeastern Louisiana were fed on the ears of rabbits. After oviposition and egg hatching, the resulting larvae were fed on mice that had been needle-inoculated with two different strains of B. burgdorferi sensu stricto, B31 and JD1. Larvae were found to be positive for spirochetes. Additional fed larvae were allowed to molt into the nymphal stage. Flat nymphs remained infected with B. burgdorferi. Infected nymphs were allowed to feed on naïve mice, all of which became infected as shown by culture of ear biopsy specimens. Naïve larvae were then fed on these same mice to assess transmissibility. The resulting engorged larvae harbored spirochetes. We have demonstrated that the I. scapularis ticks found in Louisiana are fully competent to carry and transmit B. burgdorferi infection.

Ixodes scapularis ticks (Acari: Ixodidae) from Louisiana are competent to transmit Borrelia burgdorferi, the agent of Lyme borreliosis.

We explored the possibility of using normal adult rhesus macaques for the preclinical assessment of safety, immunogenicity, and efficacy of newly developed vaccines against Streptococcus pneumoniae infection of the lung.

Experimental infection of rhesus macaques with Streptococcus pneumoniae: a possible model for vaccine assessment.

While alcohol consumption is known to increase the incidence and severity of infections, the impact of alcohol consumption on human immunodeficiency virus (HIV) disease progression has been difficult to assess. Therefore, we examined the effect of ethanol on simian immunodeficiency virus (SIV) disease progression in a well-defined model utilizing rhesus macaques.

Chronic binge ethanol consumption accelerates progression of simian immunodeficiency virus disease.

Borrelia burgdorferi, the Lyme disease pathogen, employs several immune-evasive strategies to survive in mammals. Unlike mice, major reservoir hosts for B. burgdorferi, rabbits are considered to be nonpermissive hosts for persistent infection. Antigenic variation of the VlsE molecule is a probable evasion strategy known to function in mice. The invariable region 6 (IR6) and carboxyl-terminal domain (Ct) of VlsE elicit dominant antibody responses that are not protective, perhaps to function as decoy epitopes that protect the spirochete. We sought to determine if either of these characteristics of VlsE differed in rabbit infection, contributing to its reputed nonpermissiveness. VlsE recombination was observed in rabbits that were given inoculations with either cultured or host-adapted spirochetes. Early observations showed a lack of anti-C6 (a peptide encompassing the IR6 region) response in most rabbits, so the anti-Ct and anti-C6 responses were monitored for 98 weeks. Anti-C6 antibody appeared as late as 20 weeks postinoculation, and the anti-Ct response, evident within the first 2 weeks, oscillated for prolonged periods of time. These observations, together with the recovery of cultivable spirochetes from tissue of one animal at 98 weeks postinoculation, challenge the notion that the rabbit cannot harbour a long-term B. burgdorferi infection.

Antigenicity and recombination of VlsE, the antigenic variation protein of Borrelia burgdorferi, in rabbits, a host putatively resistant to long-term infection with this spirochete.

Over 10 mo, 287 mouse litters were cross-fostered by using 1 of 2 paradigms to eliminate murine norovirus (MNV), Helicobacter spp., murine hepatitis virus (MHV), and Syphacia obvelata. Paradigm 1 involved cross-fostering litters at younger than 48 h with no attention to the changing of bedding material. Paradigm 2 involved cross-fostering litters at younger than 24 h from cages in which the bedding material was changed within 24 h before cross-fostering. After cross-foster rederivation, mice were tested for the presence of Helicobacter spp. by means of fecal PCR at 4, 8, and 12 wk. Surrogates also were tested for MNV by use of multiplex fluorometric assay serology at 4 wk and fecal PCR at 12 wk. Surrogate mice were tested for MHV by means of MFIA at 4 wk and for pinworms by perianal tape test and fecal flotation at 4 and 12 wk. Compared with those from paradigm 1, litters from paradigm 2 were less likely to be positive for MHV and Helicobacter spp. The use of cross-foster rederivation alone was unsuccessful for the elimination of Syphacia obvelata. For cross-foster rederivation, we recommend that litters be younger than 24 h and from cages in which the bedding material was changed within 24 h before cross-fostering. The presence of MNV, Helicobacter spp., and MHV can be predicted reliably at 12, 8, and 4 wk, respectively.

The use of cross-foster rederivation to eliminate murine norovirus, Helicobacter spp., and murine hepatitis virus from a mouse colony.

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The persistence of symptoms in Lyme disease patients following antibiotic therapy, and their causes, continue to be a matter of intense controversy. The studies presented here explore antibiotic efficacy using nonhuman primates. Rhesus macaques were infected with B. burgdorferi and a portion received aggressive antibiotic therapy 4-6 months later. Multiple methods were utilized for detection of residual organisms, including the feeding of lab-reared ticks on monkeys (xenodiagnosis), culture, immunofluorescence and PCR. Antibody responses to the B. burgdorferi-specific C6 diagnostic peptide were measured longitudinally and declined in all treated animals. B. burgdorferi antigen, DNA and RNA were detected in the tissues of treated animals. Finally, small numbers of intact spirochetes were recovered by xenodiagnosis from treated monkeys. These results demonstrate that B. burgdorferi can withstand antibiotic treatment, administered post-dissemination, in a primate host. Though B. burgdorferi is not known to possess resistance mechanisms and is susceptible to the standard antibiotics (doxycycline, ceftriaxone) in vitro, it appears to become tolerant post-dissemination in the primate host. This finding raises important questions about the pathogenicity of antibiotic-tolerant persisters and whether or not they can contribute to symptoms post-treatment.

Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection.

La persistance des sympt&ocirc;mes chez les patients atteints de la maladie de Lyme suite &agrave; une antibioth&eacute;rapie et leurs causes, continuent de faire l&#39;objet d&#39;une vive controverse. Les &eacute;tudes pr&eacute;sent&eacute;es ici explorent antibiotique son efficacit&eacute;, l&#39;utilisation de primates non humains. Macaques rh&eacute;sus ont &eacute;t&eacute; infect&eacute;es par b. burgdorferi et une partie a re&ccedil;u un traitement antibiotique agressif 4-6 mois plus tard. Plusieurs m&eacute;thodes ont &eacute;t&eacute; utilis&eacute;es pour la d&eacute;tection d&#39;organismes r&eacute;siduelles, y compris l&#39;alimentation des tiques &eacute;lev&eacute;s en laboratoire sur des singes (x&eacute;nodiagnostic), culture, immunofluorescence et PCR. R&eacute;ponses d&#39;anticorps au peptide b. burgdorferi sp&eacute;cifiques C6 diagnostique ont &eacute;t&eacute; mesur&eacute;s longitudinalement et a diminu&eacute; chez tous les animaux trait&eacute;s. L&#39;antig&egrave;ne b. burgdorferi, ADN et l&#39;ARN ont &eacute;t&eacute; d&eacute;tect&eacute;es dans les tissus des animaux trait&eacute;s. Enfin, un petit nombre de spiroch&egrave;tes intacts ont &eacute;t&eacute; r&eacute;cup&eacute;r&eacute; par x&eacute;nodiagnostic des singes trait&eacute;s. Ces r&eacute;sultats d&eacute;montrent que b. burgdorferi peut r&eacute;sister &agrave; un traitement antibiotique, administr&eacute; post-dissemination, dans un h&ocirc;te de primate. Bien que b. burgdorferi ne conna&icirc;t pas de poss&eacute;der des m&eacute;canismes de r&eacute;sistance et est sensible aux antibiotiques standards (doxycycline, ceftriaxone) in vitro, elle semble devenir tol&eacute;rante post-dissemination dans l&#39;accueil de primate. Cette constatation soul&egrave;ve d&#39;importantes questions sur le pouvoir pathog&egrave;ne des d&eacute;linquants chroniques antibiotiques tol&eacute;rants et si oui ou non ils peuvent contribuer le traitement des sympt&ocirc;mes.

Persistance de Borrelia burgdorferi chez les Macaques rh&eacute;sus apr&egrave;s traitement antibiotique d&#39;Infection diss&eacute;min&eacute;e.

Die Persistenz der Symptome bei Borreliose-Patienten, die nach Antibiotika-Therapie und deren Ursachen, weiterhin intensiv kontrovers diskutiert werden. Die hier vorgestellten Studien erforschen antibiotische Wirksamkeit mit nicht-menschlichen Primaten. Rhesus-Makaken mit B. Burgdorferi infiziert waren und ein Teil erhielt aggressiven antibiotischen Therapie 4-6 Monate sp&auml;ter. Mehrere Methoden wurden f&uuml;r die Erkennung von residual Organismen, einschlie&szlig;lich die Verf&uuml;tterung von Lab aufgezogenen Ticks auf Affen (Xenodiagnosis), Kultur, Immunfluoreszenz und PCR eingesetzt. Antik&ouml;rper-Reaktionen auf die B. Burgdorferi-spezifische C6 diagnostische Peptid waren in L&auml;ngsrichtung gemessen und sank bei allen behandelten Tieren. B. Burgdorferi Antik&ouml;rper, DNA und RNA gefunden in den Geweben von behandelten Tieren. Schlie&szlig;lich waren eine kleine Gruppe intakt Spirochetes von Xenodiagnosis von behandelten Affen wiederhergestellt. Diese Ergebnisse zeigen, dass B. Burgdorferi antibiotische Behandlung, administrierten Post-dissemination, in einem Primas-Host standhalten kann. B. Burgdorferi ist nicht bekannt, dass Resistenzmechanismen besitzen und ist anf&auml;llig f&uuml;r die Norm Antibiotika (Doxycyclin, Ceftriaxon) in-vitro-, scheint es, tolerant Post-dissemination in den Primas-Host zu werden. Diese Erkenntnis wirft wichtige Fragen &uuml;ber die Pathogenit&auml;t der Antibiotikum-toleranten Persisters und ob sie zur Nachbehandlung der Symptome beitragen k&ouml;nnen.

Persistenz von Borrelia Burgdorferi in Rhesus-Makaken nach antibiotischer Behandlung von disseminierte Infektion.

La persistenza dei sintomi in pazienti con malattia di Lyme dopo terapia antibiotica e le loro cause, continuano ad essere una questione di intensa polemica. Gli studi presentati qui esplorano efficacia antibiotica utilizzando primati. Macachi Rhesus sono stati infettati con b. burgdorferi e una porzione ricevuto aggressiva terapia antibiotica di 4-6 mesi pi&ugrave; tardi. Pi&ugrave; metodi sono stati utilizzati per il rilevamento di residui organismi, tra cui l&#39;alimentazione delle zecche allevati in laboratorio su scimmie (xenodiagnosis), cultura, immunofluorescenza e PCR. Risposte anticorpali per il peptide diagnostico del b. burgdorferi specifici C6 sono state misurate longitudinalmente e declinate in tutti gli animali trattati. B. burgdorferi antigen, DNA e RNA sono stati rilevati nei tessuti degli animali trattati. Infine, un piccolo numero di spirochete intatti sono stato recuperato da xenodiagnosis da scimmie trattate. Questi risultati dimostrano che b. burgdorferi pu&ograve; sopportare il trattamento antibiotico, somministrato post-dissemination, in un host di primate. Se b. burgdorferi &egrave; suscettibile agli standard antibiotici (Doxiciclina, ceftriaxone) in vitro e non &egrave; noto per possedere meccanismi di resistenza, sembra diventare tollerante post-dissemination nell&#39;host di primate. Questa constatazione solleva questioni importanti circa la patogenicit&agrave; di persisters antibiotico-resistenti e se non pu&ograve; contribuire alla post-trattamento i sintomi.

Persistenza di Borrelia burgdorferi nei macachi Rhesus dopo trattamento antibiotico dell&#39;infezione disseminata.

&#x6297;&#x751F;&#x7269;&#x8CEA;&#x7642;&#x6CD5;&#x3068;&#x305D;&#x306E;&#x539F;&#x56E0;&#x6B21;&#x306E;&#x30E9;&#x30A4;&#x30E0;&#x75C5;&#x60A3;&#x8005;&#x306E;&#x75C7;&#x72B6;&#x306E;&#x6C38;&#x7D9A;&#x6027;&#x3092;&#x5F15;&#x304D;&#x7D9A;&#x304D;&#x6FC0;&#x3057;&#x3044;&#x8AD6;&#x4E89;&#x306E;&#x554F;&#x984C;&#x306B;&#x306A;&#x308A;&#x307E;&#x3059;&#x3002;&#x3053;&#x3053;&#x306B;&#x63D0;&#x793A;&#x7814;&#x7A76;&#x4EE5;&#x5916;&#x306E;&#x970A;&#x9577;&#x985E;&#x3092;&#x7528;&#x3044;&#x305F;&#x6297;&#x751F;&#x7269;&#x8CEA;&#x306E;&#x6709;&#x52B9;&#x6027;&#x3092;&#x63A2;&#x308B;&#x3002;&#x30A2;&#x30AB;&#x30B2;&#x30B6;&#x30EB; B. &#x30DC;&#x30EC;&#x30EA;&#x30A2;&#x30D6;&#x30EB;&#x30B0;&#x30C9;&#x30EB;&#x30D5;&#x30A7;&#x30EA;&#x306B;&#x611F;&#x67D3;&#x3057;&#x305F;&#x3057;&#x3001;&#x4E00;&#x90E8;&#x7A4D;&#x6975;&#x7684;&#x306A;&#x6297;&#x751F;&#x7269;&#x8CEA;&#x7642;&#x6CD5;&#x53D7;&#x4FE1;&#x3057;&#x305F; 4-6 &#x30F6;&#x6708;&#x5F8C;&#x3002;&#x8907;&#x6570;&#x306E;&#x30E1;&#x30BD;&#x30C3;&#x30C9;&#x306F;&#x30E9;&#x30DC;&#x98FC;&#x80B2;&#x30B5;&#x30EB; &#xFF08;xenodiagnosis&#xFF09;&#x3001;&#x6587;&#x5316;&#x3001;&#x86CD;&#x5149;&#x6297;&#x4F53;&#x6CD5;&#x304A;&#x3088;&#x3073; PCR &#x306E;&#x30C0;&#x30CB;&#x306E;&#x990C;&#x3092;&#x542B;&#x3080;&#x3001;&#x6B8B;&#x7559;&#x306E;&#x751F;&#x7269;&#x306E;&#x691C;&#x51FA;&#x306E;&#x305F;&#x3081;&#x306B;&#x6D3B;&#x304B;&#x3055;&#x308C;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;B. &#x30DC;&#x30EC;&#x30EA;&#x30A2;&#x30D6;&#x30EB;&#x30B0;&#x30C9;&#x30EB;&#x30D5;&#x30A7;&#x30EA;&#x56FA;&#x6709; C6 &#x306E;&#x8A3A;&#x65AD;&#x30DA;&#x30D7;&#x30C1;&#x30C9;&#x6297;&#x4F53;&#x53CD;&#x5FDC;&#x3055;&#x308C;&#x305F;&#x9577;&#x624B;&#x65B9;&#x5411;&#x6E2C;&#x5B9A;&#x3057;&#x3001;&#x3059;&#x3079;&#x3066;&#x306E;&#x6271;&#x308F;&#x308C;&#x305F;&#x52D5;&#x7269;&#x3067;&#x6E1B;&#x5C11;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;B. &#x30DC;&#x30EC;&#x30EA;&#x30A2;&#x30D6;&#x30EB;&#x30B0;&#x30C9;&#x30EB;&#x30D5;&#x30A7;&#x30EA;&#x6297;&#x539F;&#x3001;DNA &#x3068; RNA &#x304C;&#x6271;&#x308F;&#x308C;&#x305F;&#x52D5;&#x7269;&#x306E;&#x7D44;&#x7E54;&#x3067;&#x691C;&#x51FA;&#x3055;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;&#x6700;&#x5F8C;&#x306B;&#x3001;&#x5C0F;&#x3055;&#x306A;&#x6570;&#x5B57;&#x305D;&#x306E;&#x307E;&#x307E;&#x30B9;&#x30D4;&#x30ED;&#x30D8;&#x30FC;&#x30BF;&#x306E;&#x6271;&#x308F;&#x308C;&#x305F;&#x30B5;&#x30EB;&#x304B;&#x3089; xenodiagnosis &#x306B;&#x3088;&#x3063;&#x3066;&#x56DE;&#x5FA9;&#x3055;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x7D50;&#x679C;&#x306F;&#x3001;&#x305D;&#x306E; B. &#x30DC;&#x30EC;&#x30EA;&#x30A2;&#x30D6;&#x30EB;&#x30B0;&#x30C9;&#x30EB;&#x30D5;&#x30A7;&#x30EA;&#x306F;&#x6297;&#x751F;&#x7269;&#x8CEA;&#x306E;&#x6CBB;&#x7642;&#x306F;&#x3001;&#x6295;&#x4E0E;&#x306E; post-dissemination &#x970A;&#x9577;&#x985E;&#x306E;&#x30DB;&#x30B9;&#x30C8;&#x306B;&#x8010;&#x3048;&#x308B;&#x3053;&#x3068;&#x304C;&#x3067;&#x304D;&#x307E;&#x3059;&#x3092;&#x793A;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;B. &#x30DC;&#x30EC;&#x30EA;&#x30A2;&#x30D6;&#x30EB;&#x30B0;&#x30C9;&#x30EB;&#x30D5;&#x30A7;&#x30EA;&#x62B5;&#x6297;&#x30E1;&#x30AB;&#x30CB;&#x30BA;&#x30E0;&#x3092;&#x6240;&#x6709;&#x3059;&#x308B;&#x77E5;&#x3089;&#x308C;&#x3066;&#x3044;&#x306A;&#x3044;&#x3068;&#x3001;&#x6A19;&#x6E96;&#x7684;&#x306A;&#x6297;&#x751F;&#x7269;&#x8CEA;&#x306B; &#xFF08;&#x30C9;&#x30AD;&#x30B7;&#x30B5;&#x30A4;&#x30AF;&#x30EA;&#x30F3;&#x3001;&#x30BB;&#x30D5;&#x30C8;&#x30EA;&#x30A2;&#x30AD;&#x30BD;&#x30F3;&#xFF09; in vitro &#x611F;&#x53D7;&#x6027;&#x3067;&#x3059;&#x304C;&#x3001;&#x305D;&#x308C;&#x306F;&#x30C8;&#x30EC;&#x30E9;&#x30F3;&#x30C8; post-dissemination &#x970A;&#x9577;&#x985E;&#x306E;&#x30DB;&#x30B9;&#x30C8;&#x306B;&#x306A;&#x308B;&#x3053;&#x3068;&#x304C;&#x8868;&#x793A;&#x3055;&#x308C;&#x307E;&#x3059;&#x3002;&#x3053;&#x306E;&#x767A;&#x898B;&#x306F;&#x3001;&#x6297;&#x751F;&#x7269;&#x8CEA;&#x8010;&#x6027;&#x306E;&#x533B;&#x5B66;&#x3068;&#x75C7;&#x72B6;&#x306E;&#x5F8C;&#x51E6;&#x7406;&#x306B;&#x8CA2;&#x732E;&#x3067;&#x304D;&#x308B;&#x304B;&#x3069;&#x3046;&#x304B;&#x306E;&#x75C5;&#x539F;&#x6027;&#x306B;&#x95A2;&#x3059;&#x308B;&#x91CD;&#x8981;&#x306A;&#x8CEA;&#x554F;&#x3092;&#x767A;&#x751F;&#x3055;&#x305B;&#x307E;&#x3059;&#x3002;

&#x30A2;&#x30AB;&#x30B2;&#x30B6;&#x30EB;&#x306E;&#x64AD;&#x7A2E;&#x6027;&#x611F;&#x67D3;&#x75C7;&#x306E;&#x6297;&#x751F;&#x7269;&#x8CEA;&#x6CBB;&#x7642;&#x3092;&#x6B21;&#x306E;&#x30DC;&#x30EC;&#x30EA;&#x30A2;&#x30D6;&#x30EB;&#x30B0;&#x30C9;&#x30EB;&#x30D5;&#x30A7;&#x30EA;&#x306E;&#x6C38;&#x7D9A;&#x6027;&#x3002;

&#xB77C;&#xC784; &#xC9C8;&#xBCD1; &#xD658;&#xC790; &#xD56D;&#xC0DD;&#xC81C; &#xCE58;&#xB8CC;, &#xADF8;&#xB9AC;&#xACE0; &#xADF8;&#xB4E4;&#xC758; &#xC6D0;&#xC778;&#xC5D0; &#xB530;&#xB77C; &#xC99D;&#xC0C1;&#xC758; &#xC9C0; &#xC18D;&#xC131; &#xAC15;&#xB82C;&#xD55C; &#xB17C;&#xB780;&#xC758; &#xBB38;&#xC81C;&#xAC00; &#xACC4;&#xC18D;. &#xC5EC;&#xAE30;&#xC5D0; &#xC81C;&#xC2DC; &#xB41C; &#xC5F0;&#xAD6C; &#xD0D0;&#xAD6C; &#xD56D;&#xC0DD;&#xC81C; &#xD6A8;&#xB2A5; nonhuman &#xC601;&#xC7A5;&#xB958;&#xB97C; &#xC0AC;&#xC6A9; &#xD558; &#xC5EC;. &#xBD89;&#xC740; &#xD138; &#xC6D0;&#xC22D;&#xC774; B. burgdorferi &#xAC10;&#xC5FC; &#xB410;&#xB2E4; &#xACE0; &#xC77C;&#xBD80; 4-6 &#xAC1C;&#xC6D4; &#xD6C4; &#xC801;&#xADF9;&#xC801;&#xC778; &#xD56D;&#xC0DD;&#xC81C; &#xCE58;&#xB8CC;&#xB97C; &#xBC1B;&#xC558;&#xB2E4;. &#xC6D0;&#xC22D;&#xC774; (xenodiagnosis), &#xBB38;&#xD654;, &#xBA74;&#xC5ED; &#xD615;&#xAD11; &#xAC80;&#xC0AC;, PCR&#xC5D0; &#xD2F1; &#xC5F0;&#xAD6C;&#xC18C; reared &#xBA39;&#xC774; &#xD3EC;&#xD568; &#xD55C; &#xC794;&#xB958; &#xC720;&#xAE30; &#xCCB4;&#xC758; &#xAC80;&#xCD9C;&#xC5D0; &#xB300; &#xD55C; &#xC5EC;&#xB7EC; &#xBC29;&#xBC95;&#xC740; &#xD65C;&#xC6A9; &#xD588;&#xB2E4;. B. burgdorferi &#xD2B9;&#xC815; C6 &#xC9C4;&#xB2E8; &#xD3A9;&#xD0C0;&#xC774;&#xB4DC; &#xD56D; &#xCCB4; &#xC751;&#xB2F5; longitudinally &#xCE21;&#xC815; &#xB418;&#xC5C8;&#xACE0; &#xBAA8;&#xB4E0; &#xCE58;&#xB8CC; &#xB3D9;&#xBB3C;&#xC5D0; &#xAC70;&#xBD80; &#xD588;&#xB2E4;. B. burgdorferi &#xD56D; &#xC6D0;, DNA&#xC640; RNA&#xB294; &#xCE58;&#xB8CC; &#xB3D9;&#xBB3C;&#xC758; &#xC870;&#xC9C1;&#xC5D0;&#xC11C; &#xBC1C;&#xACAC; &#xB418;&#xC5C8;&#xC2B5;&#xB2C8;&#xB2E4;. &#xB9C8;&#xC9C0;&#xB9C9;&#xC73C;&#xB85C;, &#xADF8;&#xB300;&#xB85C; spirochetes&#xC758; &#xC791;&#xC740; &#xC22B;&#xC790;&#xB294; &#xB300;&#xC6B0; &#xC6D0;&#xC22D;&#xC774;&#xC5D0;&#xC11C; xenodiagnosis&#xC5D0; &#xC758;&#xD574; &#xC7AC;&#xAE30; &#xB418;&#xC5C8;&#xB2E4;. &#xC774;&#xB7EC;&#xD55C; &#xACB0;&#xACFC; B. burgdorferi &#xD56D;&#xC0DD;&#xC81C; &#xCE58;&#xB8CC;, &#xC601;&#xC7A5;&#xB958; &#xD638;&#xC2A4;&#xD2B8;&#xC5D0;&#xC11C; &#xAD00;&#xB9AC; post-dissemination&#xB97C; &#xACAC;&#xB51C; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4; &#xBCF4;&#xC5EC; &#xC90D;&#xB2C8;&#xB2E4;. B. burgdorferi &#xC800;&#xD56D; &#xBA54;&#xCEE4;&#xB2C8;&#xC998;&#xC744;&#xAC00;&#xC9C0;&#xACE0; &#xC54C; &#xC218; &#xC5C6;&#xB294; &#xD45C;&#xC900; &#xD56D;&#xC0DD;&#xC81C; (doxycycline, ceftriaxone) &#xCCB4; &#xC678;&#xC5D0; &#xCDE8;&#xC57D; &#xD558;&#xC9C0;&#xB9CC; &#xC601;&#xC7A5;&#xB958; &#xD638;&#xC2A4;&#xD2B8; &#xAD00;&#xC6A9; post-dissemination &#xB420; &#xB098;&#xD0C0;&#xB0A9;&#xB2C8;&#xB2E4;. &#xC774; &#xCC3E;&#xB294; &#xD56D;&#xC0DD;&#xC81C;&#xC5D0; &#xAC15;&#xD55C; persisters&#xC758; &#xC5EC;&#xBD80; &#xADF8;&#xB4E4;&#xC740; &#xC99D;&#xC0C1; &#xD6C4; &#xCE58;&#xB8CC;&#xC5D0; &#xAE30;&#xC5EC;&#xD560; &#xC218; &#xC788;&#xB294; pathogenicity&#xC5D0; &#xB300; &#xD55C; &#xC911;&#xC694; &#xD55C; &#xC9C8;&#xBB38;&#xC744; &#xC62C;&#xB9BD;&#xB2C8;&#xB2E4;.

Borrelia burgdorferi &#xC804;&#xD30C; &#xAC10;&#xC5FC;&#xC758; &#xD56D;&#xC0DD;&#xC81C; &#xCE58;&#xB8CC;&#xC5D0; &#xB530;&#xB77C; &#xBD89;&#xC740; &#xD138; &#xC6D0;&#xC22D;&#xC774;&#xC5D0; &#xC9C0; &#xC18D;&#xC131;.

La persistencia de s&iacute;ntomas en pacientes de la enfermedad de Lyme despu&eacute;s de la terapia antibi&oacute;tica y sus causas, contin&uacute;an siendo un tema de intensa controversia. Los estudios presentados aqu&iacute; explorar&aacute;n eficacia antibi&oacute;tica con primates no humanos. Macacos rhesus estaban infectados con B. burgdorferi y una porci&oacute;n recibi&oacute; terapia antibi&oacute;tico agresiva 4-6 meses m&aacute;s tarde. Se utilizaron varios m&eacute;todos para la detecci&oacute;n de organismos residuales, incluyendo la alimentaci&oacute;n de garrapatas criados en laboratorio en monos (xenodiagn&oacute;stico), cultura, inmunofluorescencia y PCR. Respuestas del anticuerpo a la B. p&eacute;ptido diagn&oacute;stico de C6 burgdorferi espec&iacute;ficos fueron medidas longitudinalmente y disminuy&oacute; en todos los animales tratados. Ant&iacute;geno B. burgdorferi, ADN y ARN se detectaron en los tejidos de los animales tratados. Por &uacute;ltimo, una peque&ntilde;a cantidad de espiroqueta intacta fueron recuperada por xenodiagn&oacute;stico de monos tratados. Estos resultados demuestran que b. burgdorferi puede soportar el tratamiento antibi&oacute;tico, post-dissemination administrado, en un host de primate. Aunque B. burgdorferi desconoce poseer mecanismos de resistencia y es susceptible a los antibi&oacute;ticos est&aacute;ndar (doxiciclina, ceftriaxona) in vitro, que parece ser tolerante post-dissemination en el host de primate. Este hallazgo plantea preguntas importantes sobre la patogenicidad de persisters resistentes a antibi&oacute;ticos y si pueden contribuir a despu&eacute;s del tratamiento los s&iacute;ntomas.

Persistencia de Borrelia burgdorferi en macacos Rhesus tras el tratamiento antibi&oacute;tico de la infecci&oacute;n diseminada.

We assessed hematologic recovery, body weight, and behavior after serial blood collection in 10- to 14-wk-old C57BL/6 mice. Male and female mice (5 to 11 mice for pilot groups, 23 to 35 mice for full study groups) had either 15%, 20%, or 25% of their estimated total blood volume (TBV) collected once weekly for 6 wk. Except for those of the 25% TBV male pilot group, the weights of all mice recovered or increased from one collection to the next. The behavior of all mice, with the exception of the 25% TBV male pilot group, appeared normal throughout the study. Erythrogram value changes from baseline were analyzed at each weekly blood collection. Recovery was defined as the return of mean hemoglobin values to within 2 SD of mean baseline values. According to this definition, mice in the 15% TBV male group and 15%, 20%, and 25% TBV female groups recovered hematologically. To support the statistical definition of recovery, we compared our data with human anemia categories to assess the clinical relevance of the mouse hemoglobin values. On the basis of these data, we conclude that as much as 25% TBV can be collected once weekly from female mice for 6 wk and as much as 15% TBV can be collected once weekly from male mice for 6 wk without producing weight loss, behavioral changes, or clinically significant anemia.

Effects of weekly blood collection in C57BL/6 mice.

[This corrects the article on p. e29914 in vol. 7.].

Article	Year
Assessment of the nasopharyngeal bacterial flora of rhesus macaques: moraxella, Neisseria, haemophilus, and other genera. Journal of clinical microbiology\| PubMed ID: 12409426	2002
Alcohol unmasks simian immunodeficiency virus-induced cognitive impairments in rhesus monkeys. Alcoholism, clinical and experimental research\| PubMed ID: 12500109	2002
Strain-dependent response to cerebral ischemic preconditioning: differences between spontaneously hypertensive and stroke prone spontaneously hypertensive rats. Neuroscience letters\| PubMed ID: 12614917	2003
Induction of Plasmodium falciparum transmission-blocking antibodies in nonhuman primates by a combination of DNA and protein immunizations. Infection and immunity\| PubMed ID: 14688103	2004
Ixodes scapularis ticks (Acari: Ixodidae) from Louisiana are competent to transmit Borrelia burgdorferi, the agent of Lyme borreliosis. Journal of medical entomology\| PubMed ID: 14765677	2003
Experimental infection of rhesus macaques with Streptococcus pneumoniae: a possible model for vaccine assessment. Journal of medical primatology\| PubMed ID: 16764668	2006
Chronic binge ethanol consumption accelerates progression of simian immunodeficiency virus disease. Alcoholism, clinical and experimental research\| PubMed ID: 17010145	2006
Antigenicity and recombination of VlsE, the antigenic variation protein of Borrelia burgdorferi, in rabbits, a host putatively resistant to long-term infection with this spirochete. FEMS immunology and medical microbiology\| PubMed ID: 17596185	2007
The use of cross-foster rederivation to eliminate murine norovirus, Helicobacter spp., and murine hepatitis virus from a mouse colony. Journal of the American Association for Laboratory Animal Science : JAALAS\| PubMed ID: 19049248	2008
Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection. PloS one\| PubMed ID: 22253822	2012
Effects of weekly blood collection in C57BL/6 mice. Journal of the American Association for Laboratory Animal Science : JAALAS\| PubMed ID: 22330715	2011
Correction: Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection. PloS one\| PubMed ID: 24116243	2013

Jeanette E. Purcell

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