RESUMO
BACKGROUND: Multiple Sclerosis (MS) patients should cope effectively with problems of life and with problems originating from the disease. This is important because it affects the course of the disease, psychiatric morbidity, and quality of life. OBJECTIVE: This study was carried out as an intervention design with a control group to assess the effects of psychoeducation on MS patients' ways of coping with stress, psychiatric symptoms, and qualities of life. SUBJECTS AND METHODS: A total of 80 MS patients affiliated with the MS Association of Turkey were included and randomly assigned into intervention and control groups. An 8-week psychoeducation program was offered to the intervention group, whereas the control group was not given any treatment during the same period. Data were collected using a Descriptive Information Form, the Ways of Coping Inventory, the Brief Symptom Inventory, and the MS Quality of Life-54 scale. RESULTS: Based on the study, among the ways of coping with stress, problem-focused approach increased, whereas the emotional-focused approach decreased statistically significantly in the intervention group. Among the psychiatric symptoms, the levels of anxiety, depression, and somatization decreased. However, there was no significant change in the negative self-concept and hostility symptoms. The total quality-of-life scores increased significantly (P < 0.05). In the intervention group, these effects continued in the three-month-follow-up measurement. The control group showed no statistically significant change in the same parameters during the same periods. It is recommended that group psychoeducation programs should be carried out extensively in order for MS patients to cope with stress effectively and improve their mental health and quality of life.
Assuntos
Adaptação Psicológica , Promoção da Saúde/métodos , Transtornos Mentais/psicologia , Esclerose Múltipla/complicações , Educação de Pacientes como Assunto/métodos , Qualidade de Vida/psicologia , Estresse Psicológico/psicologia , Adulto , Ansiedade/epidemiologia , Aconselhamento , Depressão/epidemiologia , Feminino , Humanos , Masculino , Transtornos Mentais/etiologia , Transtornos Mentais/terapia , Saúde Mental , Pessoa de Meia-Idade , Esclerose Múltipla/psicologia , Resultado do Tratamento , TurquiaRESUMO
BACKGROUND AND OBJECTIVE: Chronic inflammatory bowel disease (IBD) demonstrates some similarities to the dysregulated chronic immunoinflammatory lesion of periodontitis. Trinitrobenzene sulphonic acid (TNBS) and dextran sodium sulphate (DSS) administered to rodents have been shown to elicit inflammatory responses that undermine the integrity of the gut epithelium in a similar manner to IBD in humans. The objective of this study was to evaluate the ability of these chemicals to elicit periodontal inflammation as a novel model for alveolar bone loss. MATERIAL AND METHODS: Mice were treated by oral application of TNBS twice a week, or with DSS in the diet over a period of 18 weeks. Alveolar bone loss was assessed on the defleshed skull using morphometric measures for area of bone resorption. RESULTS: The TNBS-treated animals tolerated oral administration with no clinical symptoms and gained weight at a similar rate to normal control animals. In contrast, DSS exerted a systemic response, including shortening of colonic tissue and liver enzyme changes. Both TNBS and DSS caused a localized action on periodontal tissues, with alveolar bone loss observed in both maxilla and mandibles, with progression in a time-dependent manner. Bone loss was detected as early as week 7, with more severe periodontitis increasing over the 18 weeks (p < 0.001). Young (7-month-old) and old (12-month-old) mice with severe combined immunodeficiency were treated with TNBS for a period of 7 weeks and did not develop significant bone loss. CONCLUSION: These data show that oral administration of TNBS or DSS provokes alveolar bone loss in concert with the autochthonous oral microbiota.
Assuntos
Perda do Osso Alveolar/induzido quimicamente , Periodontite Crônica/induzido quimicamente , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Ácido Trinitrobenzenossulfônico/efeitos adversos , Administração Oral , Processo Alveolar/efeitos dos fármacos , Animais , Colo/efeitos dos fármacos , Colo/patologia , Cistina/análise , Sulfato de Dextrana/administração & dosagem , Progressão da Doença , Fígado/efeitos dos fármacos , Doenças Mandibulares/induzido quimicamente , Doenças Maxilares/induzido quimicamente , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Periodonto/efeitos dos fármacos , Fatores de Tempo , Ácido Trinitrobenzenossulfônico/administração & dosagemRESUMO
BACKGROUND: Patients with temporomandibular joint disorders (TMD), reactive arthritis and rheumatoid arthritis often have combined etiology of hereditary and microenvironmental factors contributing to joint pain. Multiple clinical and animal studies indicate 'double-hit' inflammatory insults can cause chronic inflammation. The first inflammatory insult primes the immune system and subsequent insults elicit amplified responses. The present 'double hit' study produced a chronic orofacial pain model in mice with genetic deletion of both TNFα receptors (TNFR1/R2-/-), investigating the main nociceptive signalling pathways in comparisons to wild type mice. METHODS: An initial inflammatory insult was given unilaterally into the temporomandibular joint (TMJ). Secondary hypersensitivity was tested on the skin over the TMJ throughout the experiment. Three weeks later after complete reversal of hypersensitivity, a second inflammatory insult was imposed on the colon. Pharmacological interventions were tested for efficacy after week 10 when hypersensitivity was chronic in TNFR1/R2-/- mice. Serum cytokines were analysed at Days 1, 14, and Week 18. RESULTS: The double hit insult produced chronic hypersensitivity continuing through the 4-month experimental timeline in the absence of TNFα signalling. P2X7 and NMDA receptor antagonists temporarily attenuated chronic hypersensitivity. Serum cytokine/chemokine analysis on Day 14 when CFA induced hypersensitivity was resolved identified increased levels of pro-inflammatory cytokines CCL2, CXCL9, CXCL10, RANTES and decreased levels of anti-inflammatory cytokines IL-1ra and IL-4 in TNFR1/R2-/- compared to WT mice. CONCLUSIONS: These data suggest a causal feed-forward signalling cascade of these little studied cytokines have the potential to cause recrudescence in this orofacial inflammatory pain model in the absence of TNFα signalling. SIGNIFICANCE: Using a mouse model of chronic inflammatory temporomandibular joint disorder, we determined that absence of functional TNFR1/R2 induces aberrant inflammatory signalling caused by other increased pro-inflammatory and decreased anti-inflammatory cytokines that could serve as blood biomarkers and may predict disease progression.
Assuntos
Anti-Inflamatórios/uso terapêutico , Quimiocina CXCL9/metabolismo , Quimiocinas/química , Citocinas/metabolismo , Dor Facial/metabolismo , Hipersensibilidade/metabolismo , Inflamação/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/química , Receptores Tipo I de Fatores de Necrose Tumoral/química , Receptores do Fator de Necrose Tumoral/química , Transtornos da Articulação Temporomandibular/fisiopatologia , Articulação Temporomandibular/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Quimiocina CCL5 , Quimiocinas/metabolismo , Modelos Animais de Doenças , Humanos , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Camundongos , Receptores do Fator de Necrose Tumoral/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Fator de Necrose Tumoral alfa/químicaRESUMO
BACKGROUND: Tumor necrosis factor alpha (TNFα) is increased in patients with headache, neuropathic pain, periodontal and temporomandibular disease. This study and others have utilized TNF receptor 1/2 (TNFR1/2) knockout (KO) animals to investigate the effect of TNFα dysregulation in generation and maintenance of chronic neuropathic pain. The present study determined the impact of TNFα dysregulation in a trigeminal inflammatory compression (TIC) nerve injury model comparing wild-type (WT) and TNFR1/2 KO mice. METHODS: Chromic gut suture was inserted adjacent to the infraorbital nerve to induce the TIC model mechanical hypersensitivity. Cytokine proteome profiles demonstrated serology, and morphology explored microglial activation in trigeminal nucleus 10weeks post. RESULTS: TIC injury induced ipsilateral whisker pad mechanical allodynia persisting throughout the 10-week study in both TNFR1/2 KO and WT mice. Delayed mechanical allodynia developed on the contralateral whisker pad in TNFR1/2 KO mice but not in WT mice. Proteomic profiling 10weeks after chronic TIC injury revealed TNFα, interleukin-1alpha (IL-1α), interleukin-5 (IL-5), interleukin-23 (IL-23), macrophage inflammatory protein-1ß (MIP-1ß), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were increased more than 2-fold in TNFR1/2 KO mice compared to WT mice with TIC. Bilateral microglial activation in spinal trigeminal nucleus was detected only in TNFR1/2 KO mice. p38 mitogen-activated protein kinase (MAPK) inhibitor and microglial inhibitor minocycline reduced hypersensitivity. CONCLUSIONS: The results suggest the dysregulated serum cytokine proteome profile and bilateral spinal trigeminal nucleus microglial activation are contributory to the bilateral mechanical hypersensitization in this chronic trigeminal neuropathic pain model in the mice with TNFα dysregulation. Data support involvement of both neurogenic and humoral influences in chronic neuropathic pain.
Assuntos
Citocinas/metabolismo , Dor Facial/fisiopatologia , Hiperalgesia/fisiopatologia , Proteoma/metabolismo , Traumatismos do Nervo Trigêmeo/fisiopatologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Modelos Animais de Doenças , Dor Facial/tratamento farmacológico , Dor Facial/patologia , Temperatura Alta , Hiperalgesia/tratamento farmacológico , Hiperalgesia/patologia , Masculino , Camundongos da Linhagem 129 , Camundongos Transgênicos , Microglia/efeitos dos fármacos , Microglia/patologia , Microglia/fisiologia , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Receptores Tipo II do Fator de Necrose Tumoral/genética , Receptores Tipo II do Fator de Necrose Tumoral/metabolismo , Tato , Traumatismos do Nervo Trigêmeo/tratamento farmacológico , Traumatismos do Nervo Trigêmeo/patologiaRESUMO
In this study, Babesia microti (ATCC30222) from mice was adapted to golden hamsters. The parasite was passaged to immunosuppressed and then adapted to normal hamsters. When 30 normal hamsters were inoculated with this strain, parasitaemia increased to 74% of erythrocytes by day 7 and 70% of the hamsters died. By day 12, parasitaemia extended to 90%, with 97% mortality. Hearts and kidneys from infected animals were enlarged. Histopathology revealed acute myocarditis, hepatitis, pneumonitis, glomerulonephritis and splenomegaly. Giemsa, Acridine Orange and Rhodamine staining of the parasite were compared. Scanning electron microscopy of blood from infected hamsters revealed from 1 to 5 intra-erythrocytic parasites.
Assuntos
Babesiose , Modelos Animais de Doenças , Mesocricetus/parasitologia , Parasitemia , Doença Aguda , Animais , Babesiose/mortalidade , Babesiose/patologia , Cricetinae , Eritrócitos/parasitologia , Eritrócitos/ultraestrutura , Terapia de Imunossupressão , Masculino , Parasitemia/mortalidade , Parasitemia/patologiaRESUMO
The transformation of the parasite Trypanosoma cruzi from the blood-borne trypomastigote to the intracellular amastigote constitutes a key clinical feature in the pathophysiology of Chagas' disease. That this transition occurs without change in the integrity of the plasma membrane of the parasite suggests the presence of biochemical structures, i.e., signal transduction systems, that convey information regarding the external milieu of the host so as to facilitate this transformation. In higher eukaryotes, it has been found that a heterotrimeric GTP-binding protein (G-protein), composed of alpha beta gamma subunits, constitutes a critical component of this complex. Two closely related groups of G-proteins are substrates for cholera toxin (CT)- (Gs) and pertussis toxin (PT)- (Gi1-3 and Go) dependent ADP ribosylation. In concert, they link plasma membrane receptors to adenylate cyclase, resulting in the stimulation or inhibition, respectively, of cAMP generation. In this report, we demonstrate the presence of both groups of G-proteins. Cholera toxin-dependent ADP ribosylation of 42- and 45-kD proteins was demonstrable in amastigotes (AMAST), in the cytosol of epimastigotes (EPI), and weakly in trypomastigotes (TRYP), suggesting the presence of the stimulatory GTP-binding protein, Gs, in T. cruzi. Antisera generated against the alpha s subunit of the Gs heterotrimeric protein (anti-alpha s) bound to a 45-kD protein CT substrate in the rank order TRYP >> AMAST approximately EPI cytosol. Immunoprecipitation of CT-32P-ADP-ribosylated membranes with anti-alpha s resulted in 42- and 45-kD proteins. However, no Gs-mediated activation of adenylate cyclase was demonstrable in reconstitution studies using cyc- lymphoma cells, which lack a functional Gs but possess a beta-adrenergic receptor and adenylyl cyclase enzyme. Pertussis toxin-catalyzed ADP ribosylation was demonstrable in 39-40-kD particulate proteins of EPI, less strongly in AMAST, and least in TRYP, consistent with the presence of inhibitory (Gi) and Go GTP-binding proteins. In support of this observation, immunochemical analysis of the PT substrates identified the presence of alpha o and alpha i1-2-3 in EPI, AMAST and TRYP, although, with the exception of alpha i3, both toxin and associated immunochemical PT substrates are decreased in AMAST and TRYP relative to EPI. Although the functions of these putative G-proteins in T. cruzi are still unclear, their expression may be regulated by the state of parasite differentiation.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Proteínas de Ligação ao GTP/análise , Proteínas de Protozoários/análise , Trypanosoma cruzi/química , Difosfato de Adenosina/metabolismo , Toxina Adenilato Ciclase , Sequência de Aminoácidos , Animais , Western Blotting , Toxina da Cólera/metabolismo , Proteínas de Helminto , Soros Imunes/química , Dados de Sequência Molecular , Toxina Pertussis , Testes de Precipitina , Transdução de Sinais , Trypanosoma cruzi/metabolismo , Fatores de Virulência de Bordetella/metabolismoRESUMO
Recent studies suggest that Pneumocystis carinii DNA may be detected by PCR in oropharyngeal secretions in the majority of patients with P. carinii pneumonitis (PCP). However, the prevalence of P. carinii DNA in patients without PCP has not been well established. A prospective study of 258 nasal, pharyngeal, and salivary specimens from 86 individuals with AIDS, cancer or no underlying disease, and without respiratory infection, found no P. carinii DNA in any of the samples. Separately, to validate the PCR for detection of P. carinii DNA, 45 specimens from the lower respiratory tract (bronchoalveolar lavage [BAL] and sputum) from 31 patients with pneumonitis and AIDS or cancer were studied. Eleven had PCP by conventional stains and 20 did not. All patients with PCP, and none without PCP, had P. carinii DNA in BAL, sputum or both. The study indicates the prevalence of P. carinii DNA is low or absent in oropharyngeal secretions in the absence of PCP.
Assuntos
DNA Fúngico/análise , Infecções por Pneumocystis/diagnóstico , Pneumocystis , Pneumonia por Pneumocystis/diagnóstico , Sistema Respiratório/microbiologia , Síndrome da Imunodeficiência Adquirida/microbiologia , Adolescente , Adulto , Líquido da Lavagem Broncoalveolar/microbiologia , Criança , Estudos de Avaliação como Assunto , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Neoplasias/microbiologia , Infecções por Pneumocystis/microbiologia , Pneumonia por Pneumocystis/microbiologia , Reação em Cadeia da Polimerase/métodos , Estudos Prospectivos , Escarro/microbiologiaRESUMO
The GTP-binding regulatory proteins (G proteins) in the membranes of the lung parenchyma from normal, uninfected ferrets were compared to those from immunosuppressed animals with and without Pneumocystis carinii pneumonitis. In lung membranes, pertussis toxin (PT) catalyzed ADP ribosylation of a 41-kDa protein; treatment with cholera toxin (CT) led to ribosylation of a 44-kDa polypeptide. Compared to that in the normal ferrets, the level of the 44-kDa protein was dramatically suppressed in the P. carinii-infected animals. Western blot analysis with specific antibodies to alpha s (which recognized CT substrates), alpha common (which reacted to PT substrates), the alpha q/11 epitope, and the beta subunit demonstrated that these proteins were decreased in animals with P. carinii pneumonitis (PCP). Western blotting of PCP-free membranes with a pan-Ras antibody revealed a 21-kDa polypeptide (corresponding to small G proteins). The level of the 21-kDa protein in membranes from PCP-affected animals was only 30% of that in membranes from PCP-free animals. Finally, analogous studies performed with rat lung membranes revealed similar findings. These data suggest that, independent of its exacerbation of immunosuppression, PCP leads to extensive changes in the GTP-binding proteins in the lung.
Assuntos
Proteínas de Ligação ao GTP/metabolismo , Pulmão/metabolismo , Pneumonia por Pneumocystis/metabolismo , Difosfato de Adenosina/metabolismo , Animais , Western Blotting , DNA Fúngico/análise , Modelos Animais de Doenças , Furões , Técnica Indireta de Fluorescência para Anticorpo , Proteínas de Ligação ao GTP/química , Proteínas de Ligação ao GTP/imunologia , Soros Imunes/imunologia , Terapia de Imunossupressão , Masculino , Peso Molecular , Pneumocystis/genética , Pneumocystis/isolamento & purificação , Pneumonia por Pneumocystis/imunologia , Reação em Cadeia da Polimerase , Ratos , Ratos Sprague-DawleyRESUMO
Pneumocystis carinii-infected immunosuppressed ferrets and rats were searched for P. carinii cysts and trophozoites in extrapulmonary organs, including the heart, liver, stomach, kidney, and spleen. Foci of P. carinii were found in the liver or kidney of 4 (10%) of 40 ferrets but in no extrapulmonary sites of 30 rats with P. carinii pneumonitis. Attempts to identify P. carinii from immunosuppressed rat or ferret blood or propagate the organism intraorbitally in immunosuppressed rats were unsuccessful. Pneumocystis carinii was identified from aspirated stomach contents of ferrets but in none of the rats infected with P. carinii pneumonitis.
Assuntos
Modelos Animais de Doenças , Furões , Infecções por Pneumocystis/microbiologia , Pneumocystis/isolamento & purificação , Ratos Sprague-Dawley , Animais , Olho/microbiologia , Infecções Oculares Fúngicas/imunologia , Infecções Oculares Fúngicas/microbiologia , Técnica Indireta de Fluorescência para Anticorpo , Fungemia/microbiologia , Coração/microbiologia , Terapia de Imunossupressão , Rim/microbiologia , Fígado/microbiologia , Pulmão/microbiologia , Masculino , Pneumocystis/ultraestrutura , Infecções por Pneumocystis/imunologia , Ratos , Baço/microbiologia , Estômago/microbiologiaAssuntos
Dexametasona/efeitos adversos , Imunossupressores/efeitos adversos , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/farmacologia , Pneumonia por Pneumocystis/etiologia , Sirolimo/efeitos adversos , Tacrolimo/efeitos adversos , Animais , Humanos , Pneumonia por Pneumocystis/prevenção & controle , RatosAssuntos
Anticorpos/análise , Doenças dos Bovinos/imunologia , Coccidiose/veterinária , Eimeria/imunologia , Animais , Antígenos de Protozoários/imunologia , Bovinos , Doenças dos Bovinos/diagnóstico , Coccidiose/diagnóstico , Coccidiose/imunologia , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Especificidade da EspécieRESUMO
The effects of three new immunosuppressive drugs used for organ transplantation, mycophenolate mofetil, tacrolimus, and sirolimus, were compared with those of dexamethasone in provocation of Pneumocystis carinii pneumonitis in virus-free Sprague-Dawley rats. Rats injected daily with tacrolimus showed a dose-related response to the point of severe P. carinii pneumonitis 4 weeks after initiation of drug administration identical to those animals treated with high-dose dexamethasone. Thirty percent of rats treated with sirolimus had mild P. carinii infection. Surprisingly, mycophenolate mofetil had an anti-P. carinii effect. None of the animals had discernible P. carinii infection when treated with mycophenolate mofetil alone or combined with dexamethasone. Mycophenolate mofetil is unique because of its dual activity as a potent immunosuppressant as well as an antimicrobial with action against P. carinii.
Assuntos
Imunossupressores/farmacologia , Ácido Micofenólico/análogos & derivados , Pneumocystis/efeitos dos fármacos , Polienos/farmacologia , Tacrolimo/farmacologia , Animais , Dexametasona/farmacologia , Feminino , Ácido Micofenólico/farmacologia , Ratos , Ratos Sprague-Dawley , SirolimoRESUMO
Atovaquone was evaluated for the prevention and treatment of babesiosis in hamsters. When atovaquone was administered before inoculation of 10(6) Babesia microti and continued for 8 days thereafter, 9 of 10 hamsters survived beyond 54 days, but all untreated controls died within 12 days after inoculation. Quantitation of parasitemia showed a mean of 75% erythrocytes parasitized by day 5 in controls, but atovaquone recipients never exceeded 0.7% of parasitized erythrocytes over 54 days of observation. Clindamycin plus quinine was also effective but less so than atovaquone. When treatment was not started until parasitemia became established, atovaquone in doses of 300, 150, and 80 mg/kg/day was effective in the recovery of all animals compared with 50% of those receiving 10 mg/kg/day and 10% of untreated controls. With its remarkable safety record, atovaquone offers promise for clinical trials in babesiosis of both humans and lower animals.
Assuntos
Antiprotozoários/uso terapêutico , Babesiose/tratamento farmacológico , Babesiose/prevenção & controle , Naftoquinonas/uso terapêutico , Animais , Atovaquona , Quimioprevenção , Cricetinae , Dexametasona/farmacologia , Estudos de Avaliação como Assunto , Glucocorticoides/farmacologia , Terapia de Imunossupressão , Masculino , Parasitemia/tratamento farmacológico , Análise de SobrevidaRESUMO
The diagnosis of Pneumocystis carinii pneumonia (PCP) requires invasive methods of bronchoalveolar lavage and lung biopsy. In this study, we examined efficacy of polymerase chain reaction (PCR) compared to Giemsa and silver ammoniacal staining to detect P. carinii in easily accessible extrapulmonary sites as well as lung. Samples were collected from lung, nasal and pharyngeal aspirates, gastric contents, urine and blood from dexamethasone treated or untreated virus-free Sprague-Dawley rats. All immunosuppressed lung samples were P. carinii positive by PCR analysis and both stains. Respectively DNA fragments of P. carinii were found in 93%, of nasal and 75% of pharyngeal aspirates, and 0% of sera, urine or gastric aspirates from immunosuppressed rats. However, no P. carinii cysts or trophozoites were found in nasal and pharyngeal aspirates (extrapulmonary sites) by silver ammoniacal or Giemsa staining. In comparison, none of the specimens from immunocompetent rats were PCR positive at any sites tested including the lungs. Therefore, PCR amplification products of nasal and pharyngeal aspirates showed that immunosuppressed rats with PCP can carry P. carinii DNA fragments in their upper respiratory tracts, but immunocompetent animals without PCP, are free of the organism and this suggests an approach to be investigated in humans with PCP.
Assuntos
Nasofaringe/microbiologia , Pneumocystis/isolamento & purificação , Pneumonia por Pneumocystis/diagnóstico , Reação em Cadeia da Polimerase , Animais , Corantes Azur , DNA Fúngico/análise , Dexametasona/farmacologia , Modelos Animais de Doenças , Feminino , Imunocompetência , Hospedeiro Imunocomprometido , Pulmão/microbiologia , Pneumocystis/genética , Pneumonia por Pneumocystis/microbiologia , Ratos , Ratos Sprague-Dawley , Coloração pela PrataRESUMO
Several drugs have been shown to have anti-Pneumocystis carinii activity in clinical trials. Because of the large number of patients required, no more than 3 drugs can be compared for efficacy in human studies. However, the experimental animal model for P. carinii pneumonitis is remarkably similar to the human disease and was used to compare 10 drugs for the relative potency against this infection. All drugs were compared at doses known to prevent the pneumonitis in > 80% of animals and at one-tenth of this dose. Drugs effective at the lowest dose were further tested at one-hundredth the original doses, and drugs ineffective were retested at 10 and 100 times the original dose. Trimethoprim-sulfamethoxazole was the most effective drug, with azithromycin-sulfamethoxazole and clarithromycin-sulfamethoxazole next most effective. Intravenous pentamidine and clindamycin-primaquine were the least effective. Atovaquone, sulfadoxine-pyrimethamine, erythromycin-sulfisoxazole, PS-15, and dapsone-trimethoprim had intermediate activity.
Assuntos
Anti-Infecciosos/uso terapêutico , Infecções por Pneumocystis/tratamento farmacológico , Animais , Atovaquona , Azitromicina/uso terapêutico , Claritromicina/uso terapêutico , Clindamicina/uso terapêutico , Ensaios Clínicos como Assunto , Dapsona/uso terapêutico , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Quimioterapia Combinada , Humanos , Naftoquinonas/uso terapêutico , Pentamidina/uso terapêutico , Proguanil/análogos & derivados , Proguanil/uso terapêutico , Pirimetamina/uso terapêutico , Ratos , Sulfadoxina/uso terapêutico , Sulfametoxazol/uso terapêutico , Trimetoprima/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêuticoRESUMO
Dexamethasone treated rats inoculated with Trypanosoma cruzi developed acute parasitemia. In addition, these animals concomitantly developed severe Pneumocystis carinii pneumonia (PCP) and died after 4 weeks of immunosuppression (100%). However, immunocompetent (untreated) rats inoculated with T. cruzi did not acquire P. carinii and recovered from T. cruzi infection. Rats immunosuppressed, but not inoculated with T. cruzi, developed only PCP and died 5-6 weeks later (93%). In contrast, immunocompetent or immunocompromised IRC mice infected with T. cruzi all died of acute parasitemia in only 8-12 days with no detectable PCP infection. In conclusion, rats immunosuppressed and T. cruzi inoculated can serve as a MOPPS model for a single drug evaluation. In addition, T. cruzi infection independently does not provoke P. carinii pneumonia in this model. Finally, patients with Chagas' disease treated with corticosteroids may be at risk for PCP and should be considered for chemoprophylaxis.
Assuntos
Pneumocystis/patogenicidade , Pneumonia por Pneumocystis/complicações , Trypanosoma cruzi/patogenicidade , Tripanossomíase/complicações , Animais , Dexametasona/imunologia , Modelos Animais de Doenças , Avaliação de Medicamentos/métodos , Glucocorticoides/imunologia , Terapia de Imunossupressão , Camundongos , Camundongos Endogâmicos ICR , Parasitemia , Ratos , Ratos Sprague-DawleyRESUMO
The efficacy of the ionophore lasalocid against Pneumocystis carinii pneumonitis in corticosteroid-immunosuppressed Sprague-Dawley rats was investigated. Lasalocid was effective in the prevention of the pneumonitis in a dose-dependent manner. At dosages of 0, 5, 10, and 20 mg/kg/day, P. carinii infection rates were 92, 60, 20, and 0%, respectively, during dexamethasone immunosuppression. Also, lasalocid compared favorably with other drugs known to have anti-P. carinii activity, including trimethoprim-sulfamethoxazole, atovaquone, and dapsone-trimethoprim.
Assuntos
Ionóforos/uso terapêutico , Lasalocida/uso terapêutico , Pneumonia por Pneumocystis/prevenção & controle , Animais , Feminino , Ratos , Ratos Sprague-DawleyRESUMO
The corticosteroid-treated animal is well established as an experimental model for the study of Pneumocystis carinii pneumonitis (PCP). Latent or acquired infection with P. carinii in the murine lung progresses to fatal pneumonitis when the host is profoundly immunocompromized. In this study the effects of five immunomodulators; recombinant CD40 ligand (CD40L), bryostatin 1, recombinant FLT3 ligand (FLT3L), recombinant granulocyte colony-stimulating factor (G-CSF) and recombinant interleukin-15 (IL-15) were investigated against PCP in a dexamethasone immunosuppressed Sprague-Dawley rat model. The majority of rats (70%) treated with CD40L at the onset of dexamethasone immunosuppression were protected against PCP. When CD40L was given after 10 days of immunosuppression, only 40% of the rats resolved the infection. However, 95% of the control animals developed PCP. Immunosuppressed rats treated with bryostatin 1, an immune activator had a partial (50%) protection against P. carinii infection. In contrast, daily administration of FLT3L, IL-15 or G-CSF provided no protection against P. carinii infection.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Ligante de CD40/uso terapêutico , Pneumocystis/imunologia , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/imunologia , Animais , Briostatinas , Dexametasona/farmacologia , Modelos Animais de Doenças , Feminino , Terapia de Imunossupressão , Interleucina-15/genética , Interleucina-15/uso terapêutico , Lactonas/uso terapêutico , Macrolídeos , Proteínas de Membrana/genética , Proteínas de Membrana/uso terapêutico , Camundongos , Ratos , Ratos Sprague-Dawley , Proteínas RecombinantesRESUMO
The purpose of this study was to determine the period of persistence of Pneumocystis carinii in the lungs after P. carinii pneumonitis (PCP). After primary PCP was induced with dexamethasone, experimental rats were moved to a high-efficiency particulate air-filtered isolator to prevent further exposure to environmental P. carinii and allowed to recover. At intervals thereafter, sample groups were transferred to a second isolator and reimmunosuppressed with dexamethasone to provoke PCP if P. carinii were present. Reactivation of PCP was assessed by histologic examination, counts of cysts per gram of lung, and DNA amplification using nested polymerase chain reaction. A sequential and progressive decrease in P. carinii was detected. Thus, P. carinii is cleared from the lungs of > or = 75% of animals within 1 year after an episode of PCP, implying that persistence of latent organisms is limited.
Assuntos
Pulmão/microbiologia , Pneumocystis/isolamento & purificação , Pneumonia por Pneumocystis/microbiologia , Animais , Sequência de Bases , Biópsia por Agulha , Cistos/microbiologia , Cistos/patologia , DNA Bacteriano/análise , Dexametasona/farmacologia , Feminino , Pulmão/patologia , Dados de Sequência Molecular , Pneumocystis/genética , Ratos , Ratos Sprague-Dawley , RecidivaRESUMO
Because of its prevalence and severity, Babesia microti infection is an important public health problem. The current treatment of choice is clindamycin plus quinine. However, in some cases other treatments are needed because of drug intolerance or relapse. The activity of azithromycin was investigated for treatment of babesiosis in the hamster model. All animals received vancomycin to prevent antibiotic-associated colitis. Quinine (250 mg/kg/day), azithromycin (150 mg/kg/day), and the combination of azithromycin and quinine were compared. A significant suppression of parasitemia was found in all treatment groups (combination had the greatest effect, followed by azithromycin, then quinine; P < .05). The mean survival was significantly prolonged in the combination group (P < .05). Azithromycin as monotherapy in a higher dose (300 mg/kg/day) also resulted in a significant prolongation of survival (P < .05). Spirogermanium and ciprofloxacin, which have been reported to have antimalarial activity, had no effect on parasitemia or survival in this experimental babesiosis model.