RESUMO
To discuss the effect of varicella vaccination on the clinical characteristics of herpes zoster (shingles) cases aged 20 years and under, and analyze its clinical features. Based on the Yichang Health Big Data Platform, a descriptive study was conducted to collect the information of cases aged 20 years and under in three medical institutions of Yichang Central People's Hospital, Yichang First People's Hospital and Yichang Second People's Hospital from March 2019 to September 2020. According to the history of varicella vaccine, cases were divided into vaccination group and non-vaccination group, and their clinical features and outcomes were compared. The results showed that 46 shingles cases, aged from 7 to 20 years old, were included in this study. 26 males (56.5%), 20 females (43.5%), 15 cases in vaccination group (32.6%) and 31 cases in non-vaccination group (67.4%). 28 cases had thoracic involvement, followed by lumbar (n=8), cranial (n=7) involvements and extremities (n=7). The spread of herpes skin area: 2 cases involved too large area, 21 cases of 10 cm×10 cm, 14 cases of 5 cm×5 cm, 9 cases of 1 cm×1 cm. Herpes number: 26 cases had 10-49 herpes, followed by <10 herpes (n=9), uncountable herpes (n=7) and 50-99 herpes (n=4). The clinical course[M(Q1,Q3)] lasted 20.5 (13.5,24.8) d averagely, 5 cases had postherpetic neuralgia (PHN) and 1 case had respiratory complications. Shingles decrustation time was significantly shorter in vaccination group (Z=-2.01, P<0.05), and there was no significant difference in other characteristics by vaccination. In conclusion, the number and spread of shingles in most children and adolescents are less, and the complications such as PHN are less. Varicella vaccination can reduce the decrustation time and relieve shingles cases with some clinical symptoms.
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Varicela , Vacina contra Herpes Zoster , Herpes Zoster , Neuralgia Pós-Herpética , Adolescente , Criança , Feminino , Humanos , Masculino , Adulto Jovem , Varicela/epidemiologia , Varicela/prevenção & controle , Herpes Zoster/epidemiologia , Herpes Zoster/prevenção & controle , Vacina contra Herpes Zoster/uso terapêutico , Herpesvirus Humano 3 , Neuralgia Pós-Herpética/prevenção & controleRESUMO
To explore the characteristics of big data of patients with allergic rhinitis, including the time, population and spatial distribution of allergic rhinitis in Beijing from 2016 to 2021, so as to provide reference for the prevention and treatment of this disease. Descriptive epidemiological methods were used to analyze the distribution (including gender, age and location)and trend of allergic rhinitis patients in 30 pilot hospitals from January 2016 to December 2021, T test and Kruskal-Wallis rank sum test were used to test the statistical differences. The results showed that the number of patients with allergic rhinitis in 30 hospitals increased year by year from 2016 to 2019, with an increase of 97.9%. In 2020, the number of patients decreased. In 2021, the number of visits returned to the pre-epidemic level (461 332); The number of patients with allergic rhinitis was the highest in September, with a seasonal index of 177.6%, while the lowest number was in February, accounting for only 47.2%; a significant difference was observed in the number of patients in different age groups(H=45 319.48, P<0.05), and patients under 15 years old accounted for the highest proportion(819 284 visits); There were significant differences between patients of different genders in the 45-59 year old group (t=-4.26, P<0.05).There were relatively more patients with allergic rhinitis in Dongcheng District(31.1%) than in Huairou District and Miyun District (0.4%). In conclusion, since 2016, the number of patients increased significantly, with a varied trend in different seasons. Most patients were children. There were more patients in the central urban area than in the outer suburbs.
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Epidemias , Rinite Alérgica , Criança , Humanos , Feminino , Masculino , Adolescente , Pessoa de Meia-Idade , Pequim/epidemiologia , Big Data , Hospitais , Rinite Alérgica/epidemiologiaRESUMO
Objective: To explore the relationship between exposure to famine in early life and the risk of hypertension in adulthood. Methods: The medical data of Yichang Health Management Big Data Center from 2018 to 2019 were analyzed. A retrospective cohort study design was adopted, with hypertension as the study outcome, and different life periods exposed to the Great Famine in China were divided into groups. Multivariate logistic regression model was used to analyze the relationship between famine exposure in early life and hypertension in adulthood. At the same time, the interaction between gender and famine exposure was analyzed. Results: The age of 142 016 subjects was (60. 56±4.43). Among them, men accounted for 46.36% (65 845/142 016) and women accounted for 53.64% (76 171/142 016). There are 42 575(29.98%), 19 644(13.83%), 28 405(20.00%), 28 305(19.93%), 23 087 (19.93%) in non-famine exposure group, fetal famine exposure group, early childhood famine exposure group and late childhood famine exposure group, respectively. The prevalence of hypertension was 17.57% (24 947 cases). Multivariate logistic regression model analysis showed that after adjusting for related confounding factors, compared with non-famine exposure group, the risk of hypertension in fetal, early childhood, middle childhood and late childhood famine exposure group was higher and the OR (95%CI) values were 1.16 (1.11-1.22), 1.27 (1.21-1.33), 1.54 (1.47-1.60) and 1.84 (1.76-1.92), respectively. There was an interaction between sex and famine exposure group (P<0.001). The above association is stronger among women than among men. Conclusion: Famine exposure in early life may increase the risk of hypertension in adulthood, and the risk of women is greater than that of men.
Assuntos
Hipertensão , Efeitos Tardios da Exposição Pré-Natal , Inanição , Adulto , Criança , Pré-Escolar , China/epidemiologia , Fome Epidêmica , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/etiologia , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos RetrospectivosRESUMO
Based on Yichang health big data platform, 850 608 patients from September 2018 to September 2019 were included in this study. According to the date of birth, the participants were divided into early childhood famine exposure group, fetal famine exposure group and non-famine exposure group. The incidence of adult herpes zoster (HZ) in Yichang city was analyzed, and the correlation between early life famine exposure and adult HZ was analyzed. In 2019, the crude incidence rate of adult HZ in Yichang was 6.83. The crude incidence rate of adult HZ in females (7.26) was higher than that in males (6.40). Compared with the non-famine exposure group, fetal famine exposure was associated with the incidence of adult HZ (OR=1.21; 95%CI: 1.01-1.45, P=0.041). After stratification by sex, fetal famine exposure was only found to be associated with the onset of adult HZ in females (OR=1.28, 95%CI:1.02-1.61, P=0.034).
Assuntos
Herpes Zoster , Efeitos Tardios da Exposição Pré-Natal , Adulto , Pré-Escolar , Fome Epidêmica , Feminino , Herpes Zoster/epidemiologia , Humanos , Incidência , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologiaRESUMO
Objective: To analyze the genetic characteristics of varicella-zoster virus (VZV) in people aged 20 years and under in Yichang City of Hubei Province from 2019 to 2020. Methods: Based on the Yichang Health Big Data Platform, we investigated cases 20 and under clinically diagnosed as herpes zoster in three hospitals from March 2019 to September 2020. Collecting vesicle fluid and throat swab samples of the cases and completing questionnaires to obtain basic information. Real-time fluorescent quantitative PCR was used for positive identification of the virus. PCR amplification of VZV's open reading frame (ORF) and sequencing of the products to determine the VZV genotype. Analyze mutations at some specific single nucleotide polymorphism (SNP) sites. Results: Among 46 cases of herpes zoster, the male to female ratio was 1.3â¶1 (26â¶20) and the age ranged from 7 to 20 years old. Fifteen cases had been vaccinated against varicella, including 13 and 2 cases of 1 and 2 doses, respectively. VZV strains were detected in 34 samples (73.91%), all belonging to Clade 2. Phylogenetic tree analysis of the nucleotide of ORF22 showed, compared with Clade 2 referenced strains, the sequence matching degree of nucleotide for all 34 samples was 99.0% to 100.0%. Conclusion: The main VZV strain causing herpes zoster in people aged 20 years and under in Yichang from 2019 to 2020 was Clade 2.
Assuntos
Herpes Zoster , Herpesvirus Humano 3 , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Herpesvirus Humano 3/genética , Filogenia , Herpes Zoster/epidemiologia , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase em Tempo Real , NucleotídeosRESUMO
Objective: To understand the epidemiological characteristics of public health emergency events (PHEE) of varicella in China from 2006 to 2021 and related response performances. Methods: The data of varicella PHEE in 31 provinces of China from 2006 to 2021 were collected through the Public Health Emergency Management Information System, Microsoft Excel 2019 software and SPSS 26.0 statistical software were used to conduct descriptive epidemiological, statistical analysis on the time, area, location distribution, scale and epidemic management. Results: A total of 11 443 PHEE involving 341 048 related cases were reported from 2006 to 2021, with an annual attack rate of 1.78%-3.80% and a total attack rate of 2.33% (341 048/14 624 042). The number of PHEE and related cases of varicella decreased from 1 107 (35 349) in 2007 to 262 (6 884) in 2012 (Z=-2.40, P<0.001), then increased year by year to 1 318 (42 649) in 2019 (Z=2.58, P<0.001), with a significant decline since 2020. The varicella PHEE in China presents the seasonal characteristics,the peak is from April to June and from October to December, respectively. The sub-peak of varicella PHEE in eastern China generally appears 1-2 months earlier than in central and western China. Varicella PHEE reports are mainly distributed in eastern China, the attack rate is relatively high in western China, school-reported varicella PHEE was 88.26% of the total reports (10 099/11 443). The epidemic scale of varrcella PHEE typically range from 10 to 29 cases per year among the given outbreaks. The M (Q1, Q3) of average number of cases, average duration, and average reporting interval of PHEE were 23 (16,35), 20 (14, 26) days, and 9 (5,19) days, respectively, and the reporting interval was positively correlated with the duration (r=0.854, P<0.001). Conclusions: The varicella PHEE in China from 2006 to 2021 has not been effectively controlled. Schools are the key places to prevent and control varicella PHEE. Improving the sensitivity of varicella PHEE monitoring, strengthening the timely disposal of varicella epidemic, and promoting varicella vaccination are effective measures to prevent and control varicella PHEE.
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Varicela , Epidemias , Humanos , Varicela/epidemiologia , Varicela/prevenção & controle , Saúde Pública , Surtos de Doenças/prevenção & controle , China/epidemiologia , VacinaçãoRESUMO
Objective: To systematically analyze and evaluate the IgG antibody levels of varicella-zoster virus (VZV) in healthy population in China. Methods: CNKI, Wanfang, CBM and PubMed databases were used for the retrieval of literatures about VZV IgG antibody levels in healthy people in China from January 1, 2000 to November 3, 2020. The quality of the included papers was evaluated by the critical appraisal tools for cross sectional study from Joanna Briggs Institute (JBL). The stratified analysis on the IgG antibody levels in populations in different age groups, provinces, regions, gender groups, and years was performed by using software Stata 14.0. Results: A total of 59 papers were included that met the inclusion criteria, including 51 papers in Chinese and 8 papers in English. There were 22 papers with quality score of 8, 16 papers with quality score of 7, 15 papers with quality score of 6, and 6 papers with quality score of 5. Meta-analysis showed that the positive rate of VZV IgG antibody in healthy population in China was 64% (95%CI:60%-67%, I2 =98.7%), and the IgG antibody levels were reported in the papers for 22 provinces of China. The positive rate of VZV IgG antibody was highest in Yunnan (79%, 95%CI: 64%-93%, I2 =94.7%) and lowest in Inner Mongolia (50%, 95%CI: 46%-54%); the positive rate of VZV IgG antibody was highest in Northeastern China (71%, 95%CI: 69%-73%) and lowest in Eastern China (62%, 95%CI: 57%-67%); the positive rate of VZV IgG antibody in urban population was higher than that in rural population (RR=1.08, 95%CI: 1.04-1.11). The positive rate of VZV IgG antibody in women was higher than that in men (RR=1.10, 95%CI: 1.08-1.11); the positive rate of VZV IgG antibody in the population increased with age; and the positive rate of VZV IgG antibody increased with the change of sampling time. Conclusion: The positive rate of VZV IgG antibody in healthy population in China was relatively low; the coverage of varicella vaccine should be improved for the outbreak control and incidence reduction of varicella in China.
Assuntos
Varicela , Herpes Zoster , Anticorpos Antivirais , Varicela/epidemiologia , Vacina contra Varicela , China/epidemiologia , Estudos Transversais , Feminino , Herpesvirus Humano 3 , Humanos , MasculinoRESUMO
As the progress of population aging in China, the proportion of elderly population is increasing. Both chronic diseases and infectious diseases can threaten the health of the elderly. There are many kinds of infectious diseases, including vaccine preventable infectious diseases affecting the health of adults, such as influenza, pneumococcal diseases and herpes zoster. In addition, the newly emerged COVID-19 has caused a pandemic in the world, resulting the highest proportion of deaths occurred in the elderly and posing a serious threat to the health of the elderly. This paper mainly summarizes the prevention and control of vaccine preventable diseases and COVID-19 to which the elderly are susceptible, analyzes the infectious disease problems affecting the health of elderly population, and recommends countermeasures for the prevention and control of these diseases in elderly population.
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COVID-19 , Doenças Transmissíveis , Idoso , China/epidemiologia , Doenças Transmissíveis/epidemiologia , Humanos , Pessoa de Meia-Idade , SARS-CoV-2 , VacinaçãoRESUMO
The generation of knockout mice with targeted gene disruption has provided a valuable tool for studying the immune response. Here we describe the use of CD4 and CD8 knockout mice to examine the role of CD4+ and CD8+ cells in initiating allotransplantation rejection. Pretreatment with a brief course of depletive anti-CD4 monoclonal antibody therapy allowed permanent survival of heart, but not skin, allografts transplanted across a major histocompatibility barrier. However, skin as well as heart grafts were permanently accepted in the CD4 knockout mice. Transfer of CD4+ cells into CD4 knockout recipient mice 1 d before skin engraftment reconstituted rejection, demonstrating that CD4+ cells are necessary for initiating rejection of allogeneic transplants. Major histocompatibility complex disparate heart and skin allografts transplanted into CD8 knockout recipients were rejected within 10 d. This study demonstrates that CD4+ but not CD8+ T cells are absolutely required to initiate allograft rejection.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Rejeição de Enxerto/imunologia , Transplante Homólogo/imunologia , Transferência Adotiva , Animais , Antígenos CD4/genética , Antígenos CD8/genética , Sobrevivência de Enxerto , Transplante de Coração/imunologia , Depleção Linfocítica , Complexo Principal de Histocompatibilidade/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transplante de Pele/imunologia , Baço/transplanteRESUMO
We have previously shown that islet emboli in the portal vein block blood flow and induce local inflammatory reaction, resulting in functional loss of islet grafts following intraportal transplantation. This study was designed to test whether Toll-like receptor (TLR) activation mediates early islet graft failure. Syngeneic islet grafts were transplanted into chemically induced diabetic mice, and TLR deficient mice were used as donors and/or recipients of islet grafts. Islet viability, proinflammatory cytokines, high-mobility group box-1 (HMGB1) and NF-kappaB activation were analyzed by bioluminesce imaging (BLI), quantitative RT-PCR (qRT-PCR) and histology. Early islet graft failure was observed in mice with intraportal islet engrafts with increased proinflammatory cytokines, HMGB1 expression, NF-kappaB activation, caspase-3 and TUNEL positive cells. Deficiency of TLR4 in donor, but not in recipient, inhibited NF-kappaB activation, reduced proinflammatory cytokines and improved viability of islet grafts. Blockade of HMGB1 with anti-HMGB1 monoclonal antibody (mAb, 2g7) inhibited inflammatory reactions, as evidenced by reduced TNFalpha and IL-1ss production, and improved islet viability. We conclude that TLR4 activation mediates early graft failure following intraportal islet transplantation. Inhibition of TLR4 activation represents a novel strategy to attenuate early graft failure following intraportal islet transplantation.
Assuntos
Transplante das Ilhotas Pancreáticas/fisiologia , Receptor 4 Toll-Like/deficiência , Animais , Sobrevivência de Enxerto , Proteína HMGB1/genética , Interleucina-1beta/genética , Transplante das Ilhotas Pancreáticas/patologia , Rim , Fígado , Luminescência , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptor 2 Toll-Like/deficiência , Receptor 3 Toll-Like/deficiência , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/fisiologia , Transplante Heterotópico , Falha de Tratamento , Fator de Necrose Tumoral alfa/genéticaRESUMO
Objective: To analyze the clinical characteristics of pediatric external auditory canalkeratosis obturans(KO). Method: Retrospective analyze the clinical data of twenty-three patients were diagnosed with external auditory canal cholesteatoma(EACC). Their chief complaint, the course of the disease, clinical characteristics,CT manifestations,surgical procedure and prognosis were retrospectively analyzed. The clinical characteristics between EACC and KO were compared.Result: Twenty cases(22 ears) were eventually diagnosed as KO. Among them, 2 cases were bilaterally involved. In the remaining unilateral cases, right ear was involved in 11 cases and left ear in 7 cases. All patients complained otalgia(100%). Purulent otorrhea was found in 17 ears(77.3%), and hearing loss withpurulent otorrhea in 3 ears(13.6%). Otoscopic examination found 17 ear with granulation(77.3%).CT scan found deformation of the osseous ear canal and displacement of the tympanic membrane because of compression in 18 ears(81.8%), and the bony canal was absorpt because of pression in 7 cases(38.9%).All patients underwent otoendoscopic operation,and tympanic membrane perforation was found in 4 cases.Postoperative pathologic examination results were keratin epithelial. Conclusion: EACC is easily confused with KO. KO should be considered in the following circumstances: patient who complained of ear pain, ear granulation with purulent discharge, or circinate deformation of the osseous ear canal and displacement of the tympanic membrane in CT scan.
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Objective:To analyze the diagnosis and treatment of acute sinusitis or nasal furuncle derived periorbital cellulitis in children.Method:The clinical data of 18 children with acute sinusitis or nasal furuncle derived orbital cellulitis was analyzed retrospectively.Result:Sixteen cases(88.89%) had acute sinusitis and 2(11.11%) had furuncle of nose.All cases were treated with antibiotics and steroids.And 16 cases were cured and the other two received surgery.The median length of hospitalization was 7.33 days(5-13 days).Conclusion:Sufficient antibiotics combined with steroids and local treatment is critical in treating pediatric orbital cellulitis.Timely and decisive surgical intervention can effectively control the progression of disease.
Assuntos
Furunculose/diagnóstico , Celulite Orbitária/diagnóstico , Sinusite/diagnóstico , Doença Aguda , Antibacterianos , Criança , Furunculose/tratamento farmacológico , Humanos , Doenças Orbitárias , Estudos Retrospectivos , Sinusite/tratamento farmacológicoRESUMO
BACKGROUND: Vigorous antibody-mediated responses prevent the successful engraftment of hamster hearts transplanted into Lewis rats. Early antibody responses mediating acute rejection of the xenograft are T cell-independent and resistant to the T-cell immunosuppressant, cyclosporine (CsA). Immunosuppression with the combination of leflunomide plus CsA completely prevents xenograft rejection, but when such immunosuppression is stopped the hamster heart is rejected by a process that we term late xenograft rejection. We report here on some of the immunological features of late xenograft rejection. METHODS: Lewis rats transplanted with hamster hearts were treated with leflunomide (5 mg/kg/day by gavage) for 14-21 days and CsA (20 mg/kg/day by gavage) continuously from the day of transplant. Serum was harvested and the functional activities of the xenoreactive antibodies were quantitated by in vivo passive transfer of sera, flow cytometry, in vitro C3 deposition assays, and Western blotting. RESULTS: CsA alone prevented late xenograft rejection and the accompanying production of xenoreactive antibodies. The xenoreactive antibodies accompanying acute or late xenograft rejection were predominantly IgM, but only serum from rats undergoing acute xenograft rejection was able to induce hyperacute rejection. The ability of serum to induce hyperacute rejection correlated with its ability to induce C3 deposition on hamster lymphocytes in vitro. The repertoire of hamster antigens recognized by IgM in the serum of rats undergoing late xenograft rejection is more restricted than that of IgM in the serum of rats undergoing acute xenograft rejection. We additionally demonstrate that long-term graft survival is not dependent on graft accommodation. CONCLUSIONS: These studies demonstrate that a brief treatment with the combination of leflunomide and CsA profoundly modifies the humoral xenoreactivity in the recipient, converting it from a T-independent into a T cell-dependent response. Differences in functional activity of sera from acute or late xenograft rejection suggest that antigenic specificity defines the ability of IgM to induce complement activation and hyperacute rejection.
Assuntos
Ciclosporina/administração & dosagem , Rejeição de Enxerto/prevenção & controle , Transplante de Coração/imunologia , Imunossupressores/administração & dosagem , Isoxazóis/administração & dosagem , Animais , Formação de Anticorpos/efeitos dos fármacos , Complemento C3/metabolismo , Cricetinae , Imunoglobulina M/imunologia , Terapia de Imunossupressão/métodos , Leflunomida , Mesocricetus , Ratos , Ratos Endogâmicos Lew , Linfócitos T/imunologia , Fatores de TempoRESUMO
This study was designed to investigate the effectiveness of combined perioperative anti-CD4 and human (h)CTLA4Ig therapy in preventing allorejection of small bowel transplantation in high-responder Lewis rat recipients of ACI grafts. Anti-CD4 (5 mg/kg x 4 days) or hCTLA4Ig (0.5 mg/rat x 2 days) therapy alone delayed, but did not prevent, allograft rejection after small bowel transplantation of ACI into Lewis rats. All grafts were rejected in 18 and 10 days, respectively. However, a regimen of anti-CD4 (5 mg/kg x 4 days) combined with hCTLA4Ig (0.5 mg/rat x 2 days) allowed indefinite survival of ACI small bowel allografts. Second donor-matched heart grafts were permanently accepted, whereas third-party (Sprague-Dawley) heart allografts were rejected by the tolerant recipients. These data suggest that these two reagents produced a synergistic effect in preventing allorejection of small bowel transplantation.
Assuntos
Anticorpos/farmacologia , Antígenos de Diferenciação/farmacologia , Antígenos CD4/imunologia , Imunoconjugados , Imunossupressores/farmacologia , Intestino Delgado/transplante , Abatacepte , Animais , Antígenos CD , Antígeno CTLA-4 , Quimioterapia Combinada , Rejeição de Enxerto/prevenção & controle , Humanos , Tolerância Imunológica , Fragmentos Fc das Imunoglobulinas/farmacologia , Masculino , Ratos , Ratos Endogâmicos ACI , Ratos Endogâmicos Lew , Ratos Sprague-Dawley , Proteínas Recombinantes de Fusão/farmacologia , Transplante Homólogo/imunologiaRESUMO
BACKGROUND: The objective of this study was to evaluate the role of anti-Gal Abs and non-anti-Gal Abs in hyperacute rejection (HAR) of concordant pancreas xenografts compared with heart xenografts. In addition, we tested whether rejection of Lewis rat pancreas grafts was T-cell dependent and could be prevented by anti-T-cell treatment. METHODS: To determine the role of anti-Gal Abs in the induction of HAR, Lewis rat pancreas and heart xenografts were transplanted into alpha1,3Galactosyltransferase knockout (GT-Ko) mice treated with normal human serum (NHS) or hyperimmune serum, or into presensitized GT-Ko mice. To investigate whether rejection of pancreas xenograft was mediated by a T-cell dependent response, Lewis rat pancreas grafts were transplanted into streptozotocin (STZ)-induced diabetic GT-Ko mice treated with FK506, anti-CD4 mAbs (GK1.5), and thymectomy. Antidonor-specific IgM and IgG and anti-Gal Abs were analyzed by flow cytometry. Rejected and long-term surviving pancreas xenografts were assessed by functional (blood glucose) and histopathological examination. RESULTS: HAR of Lewis rat pancreas xenografts could not be induced by NHS (0.4 ml), whereas NHS (0.2 ml) resulted in HAR of Lewis heart xenografts. Infusion of Lewis rat-specific hyperimmune serum (0.2 ml) resulted in HAR of Lewis rat pancreas xenografts. In addition, second Lewis rat pancreas grafts were hyperacutely rejected by presensitized GT-Ko mice. Immunohistochemical staining showed a low expression of Galalpha1,3Gal antigen in the endocrine tissue compared with that in the cardiac grafts. The levels of anti-Gal Abs in pancreas xenograft transplantation did not increase in GT-Ko mice after pancreas xenograft transplantation that was significantly increased after heart transplantation. FK506 treatment induced long-term survival of Lewis pancreas xenografts (mean survival time (MST) >90 days). Anti-CD4 treatment delayed rejection of Lewis rat pancreas xenografts with MST of 34.3 days, whereas anti-CD4, in combination with thymectomy, synergistically prolonged survival of pancreas xenograft (MST=70.4 days). CONCLUSION: Pancreas xenograft is resistant to anti-Gal Abs-induced HAR but is susceptible to anti-donor specific Abs. Rejection of Lewis pancreas xenograft in STZ-induced, diabetic, GT-Ko mice is T-cell dependent.
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Anticorpos/imunologia , Dissacarídeos/imunologia , Rejeição de Enxerto/imunologia , Transplante de Coração , Transplante de Pâncreas , Doença Aguda , Animais , Diabetes Mellitus Experimental/cirurgia , Suscetibilidade a Doenças , Galactosiltransferases/genética , Soros Imunes/imunologia , Imunossupressores/farmacologia , Camundongos , Camundongos Knockout/genética , Pâncreas/irrigação sanguínea , Ratos , Ratos Endogâmicos Lew , Linfócitos T/fisiologia , Tacrolimo/farmacologia , Doadores de Tecidos , Transplante HeterólogoRESUMO
BACKGROUND: Ischemic-preconditioning is a process whereby a brief ischemic episode confers a state of protection against subsequent long-term ischemia-reperfusion injury. Ischemic preconditioning has been studied in heart and liver ischemia-reperfusion injury; however, few studies have been performed in the model of preservation-reperfusion injury in liver transplantation. The current study was designed to evaluate the ability of ischemic preconditioning to protect liver grafts from long-term preservation-reperfusion injury. METHODS: Male Sprague Dawley rats were used as donors and recipients of orthotopic liver transplantation. Ischemic preconditioning was done by interruption of the portal vein and hepatic artery for 5, 10, and 20 min (5-10, 10-10, and 20-10 groups). Reflow was initiated by removal of the clamp for another 10 min in all groups. The liver was removed and placed in a bath with Euro-Collins solution for different preservation times. Tolerance of the transplanted liver to cold ischemia was determined by survival time and liver function tests. Rat tumor necrosis factor was analyzed by a bioassay. Nomega-Nitro-L-arginine methyl ester, L-arginine, or adenosine was administered to block or stimulate the synthesis of nitric oxide (NO) in the rats that received long-term-preserved liver grafts. RESULTS: Twenty percent of syngeneic rats (n=10) that received a liver graft with a 16-hr cold ischemia time in Euro-Collins solution survived for more than 1 day and 10% survived for more than 5 days. In contrast, 87.5% of rats (n=8) that received a liver graft with ischemic preconditioning (10-10 group) and 16 hr of cold ischemia survived for more than 1 day and 75% for more than 5 days. Recipients of liver grafts with ischemic preconditioning had significantly reduced levels of serum aspartate transaminase and tumor necrosis factor-alpha, as well as increased bile flow, compared with recipients of liver grafts without ischemic preconditioning. Blockage of the NO pathway using Nomega-nitro-L-arginine methyl ester, a stereospecific competitive inhibitor of NO formation, attenuated the protective effect of ischemic preconditioning. Administration of one of two precursors of NO synthesis, L-arginine or adenosine, prolonged the survival of rats that received 16-hr-preserved liver grafts. In addition, L-arginine synergized with short-term ischemic pre conditioning (5-10 group) to increase the survival of rats that received a liver graft with a 16-hr cold ischemia time, and the survival rate was 83% after 5 days. Finally, prolonged ischemic preconditioning (> or = 20 min; 20-10 group) resulted in liver damage and loss of function. CONCLUSION: The current results show that ischemic preconditioning protects the liver graft from subsequent long-term cold preservation-reperfusion injury in a rat liver transplantation model. The protective role of ischemic preconditioning may be mediated by the endogenous production of NO.
Assuntos
Precondicionamento Isquêmico , Transplante de Fígado , Fígado/irrigação sanguínea , Preservação de Órgãos , Traumatismo por Reperfusão/prevenção & controle , Animais , Temperatura Baixa , Sobrevivência de Enxerto , Masculino , Óxido Nítrico/fisiologia , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/análiseRESUMO
BACKGROUND: In these experiments, we studied the role of anti-CD4 (Ox38) monoclonal antibody in the induction of allograft unresponsiveness in high-responder Lewis rats in the single liver, kidney, small bowel, and heart versus the combined heart-kidney, heart-liver, and heart-small bowel transplantation models. METHODS: ACI heart, kidney, liver, and small bowel allografts were transplanted into untreated and anti-CD4 treated Lewis rats. In selected animals bearing long-surviving ACI liver or kidney allografts for over 3 months, donor-matched second heart or third-party (Brown Norway) heart allografts were transplanted. Simultaneously, heart-liver, heart-kidney, and heart-small bowel transplants were performed on the day of operation. Rejected allografts were verified by autopsy and pathology. RESULTS: ACI liver allografts were permanently accepted by Lewis recipients treated with either regular-dose (5 mg/kg for 4 days) or low-dose (5 mg/kg for 2 days) of anti-CD4 monoclonal antibody. Pretransplant anti-CD4 therapy (5 mg/kg for 4 days but not 5 mg/kg for 2 days) resulted in a long-term survival of kidney allografts (mean survival time [MST] > 100.0 days, n=5). Pretransplant anti-CD4 treatment (5 mg/kg for 4 days) could not induce tolerance when single ACI hearts were transplanted; however, long-term survival of ACI heart allografts could be induced when heart transplants were combined with liver (n=7) or kidney (n=8) transplants. The survival of both ACI heart allografts (MST=25.0 days, n=4) and small bowel allografts (MST=28.0 days, n=4) was also prolonged when simultaneous heart and small bowel transplantation was performed in anti-CD4-treated recipients. The second ACI heart allograft was permanently accepted by tolerant Lewis recipients of ACI liver or kidney allografts induced by anti-CD4 treatment, and third-party heart grafts were acutely rejected without affecting survival of the primary allografts. CONCLUSION: Our current results show that: (1) there is a vigorous rejection of heart > or = small bowel > kidney > liver in high-responder Lewis rats after pretransplant anti-CD4 therapy; and (2) simultaneous or metachronous combined liver-heart and kidney-heart transplants may protect heart allografts from rejection.
Assuntos
Anticorpos/uso terapêutico , Antígenos CD4/imunologia , Transplante de Coração , Intestino Delgado/transplante , Transplante de Rim , Transplante de Fígado , Animais , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/fisiologia , Tolerância Imunológica/imunologia , Masculino , Ratos , Ratos Endogâmicos ACI , Ratos Endogâmicos Lew , Doadores de Tecidos , Transplante HomólogoRESUMO
We investigated the effects of pretransplant anti-CD4 monoclonal antibody (mAb) combined with human (h) CTLA4Ig on the survival of hamster heart and liver xenografts. Pretransplant anti-CD4 mAb (5 mg/kg x 4 days) or hCTLA4Ig (0.5 mg/rat on days 1, 3, and 5 after transplantation) treatment alone prolonged the survival of hamster liver xenografts in Lewis rats (mean survival time [MST]=10.5 days, n=6, and MST=9.0 days, n=5, respectively, compared with untreated Lewis recipients of hamster liver grafts, MST=6.0 days, n=6). The same regimen could not prevent hamster heart xenorejection. Pretransplant anti-CD4 mAb (5 mg/kg x 4 days) combined with hCTLA4Ig (0.5 mg/rat x 4) treatments increased survival of hamster liver xenograft fourfold (MST=24.2 days, n=5). The current results also show that IgG in the sera from Lewis recipients of hamster liver grafts treated with anti-CD4 mAb and hCTLA4Ig was threefold reduced at 6 days after transplantation compared with untreated Lewis rats. These results suggest a synergistic effect of anti-CD4 mAb combined with hCTLA4Ig in a liver xenograft transplantation model.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígenos de Diferenciação/uso terapêutico , Antígenos CD4/imunologia , Transplante de Coração/imunologia , Imunoconjugados , Transplante de Fígado/imunologia , Transplante Heterólogo/imunologia , Abatacepte , Animais , Antígenos CD , Antígeno CTLA-4 , Cricetinae , Quimioterapia Combinada , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Masculino , Mesocricetus , Ratos , Ratos Endogâmicos Lew , Proteínas Recombinantes de Fusão/uso terapêutico , Condicionamento Pré-TransplanteRESUMO
BACKGROUND: In the experiment described here, we investigated the effects of the immunosuppressants FK506 and leflunomide (Lef) on the survival of hamster hearts and liver xenografts in Lewis rats. METHODS: Lewis rats were used as recipients of hamster heart or liver grafts using different regimens of FK506 and Lef. Donor-matched heart grafts were transplanted into long-term surviving Lewis rat recipients of hamster xenografts to test donor-specific prolongation of xenograft survival. Hyperimmune, late xenograft rejection, and naive sera were transferred into long-term surviving Lewis rat recipients of hamster heart xenografts to determine whether these sera could inhibit the efficacy of donor-specific long-term survival. Anti-donor-specific antibodies were analyzed by flow cytometry. RESULTS: After a short induction with FK506 plus Lef, maintenance treatment with FK506 alone was sufficient to prolong survival of hamster xenografts. All hamster heart and four of six hamster liver xenografts survived for more than 3 months. Second hamster hearts were permanently accepted by Lewis rats bearing long-term surviving hamster heart xenografts when rats were treated with FK506 monotherapy (mean survival time >60 days, n=4). Long-term surviving hamster heart grafts were rejected after transfer of hyperimmune serum but not late xenograft rejection serum or naive serum. Lef and FK506 significantly reduced the production of anti-donor-specific antibodies in Lewis rats transplanted with hamster liver and heart xenografts. CONCLUSION: Long-term survival of hamster liver and heart xenografts in Lewis rats could be induced by a regimen of short-term FK506 in combination with Lef followed by FK506 monotherapy. The acquired sensitivity of late xenoreactivity to FK506 reflects primarily a modification in the host immune response to the hamster graft.
Assuntos
Transplante de Coração , Imunossupressores/uso terapêutico , Isoxazóis/uso terapêutico , Transplante de Fígado , Tacrolimo/uso terapêutico , Transplante Heterólogo , Animais , Anticorpos/análise , Anticorpos/imunologia , Formação de Anticorpos/efeitos dos fármacos , Cricetinae , Combinação de Medicamentos , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Soros Imunes/imunologia , Imunoglobulina G/análise , Imunoglobulina M/análise , Leflunomida , Masculino , Mesocricetus , Ratos , Doadores de TecidosRESUMO
BACKGROUND: The goal of this study was to characterize the importance of splanchnic viscera in liver ischemic reperfusion injury and to enhance the tolerance of liver to warm ischemia injury with portosystemic shunt. METHODS: The hepatic blood flow of male Sprague Dawley rats was subjected to 45, 60, 120, and 150 min liver warm ischemia with or without portosystemic shunt (splenic-caval shunt). The production of tumor necrosis factor a (TNFa), nuclear factor-kappaB activation, inducible NO synthase (iNOS) expression, and apoptosis were examined. RESULTS: A total of 67% of rats with 45 min liver warm ischemia (n=6) and 100% of rats with 60 min liver warm ischemia (n=6) died within 1 day. However, all rats with 120 min (n=8) liver warm ischemia in splenic-caval shunt group survived for over 1 day, 6/8 for over 3 days, and 5/8 for over 5 days without significant histological changes of the liver. Serum tumor necrosis factor levels in liver warm ischemic rats were increased, This increase was significantly reversed after portosystemic shunt. After challenge with lipopolysaccharide (1 mg/kg, p.v.), naive rats survived for over 5 days (n=4) with the peak value of rat tumor necrosis factor (240 pg/ml) at 90 min. In contrast, all rats died within one day (n=5) with the peak value of rat tumor necrosis factor a (465 pg/ml) at 45 min after administration of lipopolysaccharide in the rats with liver warm ischemia plus splenic-caval shunt. iNOS expression and nuclear factor-kappaB activation were very strongly increased in the hepatocytes after liver warm ischemia with portosystemic shunt, compared with liver ischemia without portosytemic shunt. CONCLUSIONS: We conclude that the splanchnic viscera can contribute to liver ischemic reperfusion injury. Portosystemic shunt enhances the tolerance of liver to warm ischemia through the protective role of iNOS and nuclear factor-kappaB (NF-kappaB).