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2.
J Clin Med ; 11(21)2022 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-36362544

RESUMEN

BACKGROUND: Mutations in spike glycoprotein, a critical protein of SARS-CoV-2, could directly impact pathogenicity and virulence. The D614G mutation, a non-synonymous mutation at position 614 of the spike glycoprotein, is a predominant variant circulating worldwide. This study investigated the occurrence of mutations in the crucial zone of the spike gene and the association of clinical symptoms with spike mutations in isolated viruses from Iranian patients infected with SARS-CoV-2 during the second and third waves of the COVID-19 epidemic in Isfahan, the third-largest city in Iran. METHODS: The extracted RNA from 60 nasopharyngeal samples of COVID-19 patients were subjected to cDNA synthesis and RT-PCR (in three overlapping fragments). Each patient's reverse transcriptase polymerase chain reaction (RT-PCR) products were assembled and sequenced. Information and clinical features of all sixty patients were collected, summarized, and analyzed using the GENMOD procedure of SAS 9.4. RESULTS: Analysis of 60 assembled sequences identified nine nonsynonymous mutations. The D614G mutation has the highest frequency among the amino acid changes. In our study, in 31 patients (51.66%), D614G mutation was determined. For all the studied symptoms, no significant relationship was observed with the incidence of D614G mutation. CONCLUSIONS: D614G, a common mutation among several of the variants of SARS-CoV-2, had the highest frequency among the studied sequences and its frequency increased significantly in the samples of the third wave compared to the samples of the second wave of the disease.

3.
J Clin Med ; 11(16)2022 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-36013032

RESUMEN

There are two main enzymes that convert tryptophan (Trp) to kynurenine (Kyn): tryptophan-2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO). Kyn accumulation can promote immunosuppression in certain cancers. In this study, we investigated Trp degradation to Kyn by IDO and TDO in primary human hepatocytes (PHH) and tumoral HepG2 cells. To quantify Trp-degradation and Kyn-accumulation, using reversed-phase high-pressure liquid chromatography, the levels of Trp and Kyn were determined in the culture media of PHH and HepG2 cells. The role of IDO in Trp metabolism was investigated by activating IDO with IFN-γ and inhibiting IDO with 1-methyl-tryptophan (1-DL-MT). The role of TDO was investigated using one of two TDO inhibitors: 680C91 or LM10. Real-time PCR was used to measure TDO and IDO expression. Trp was degraded in both PHH and HepG2 cells, but degradation was higher in PHH cells. However, Kyn accumulation was higher in the supernatants of HepG2 cells. Stimulating IDO with IFN-γ did not significantly affect Trp degradation and Kyn accumulation, even though it strongly upregulated IDO expression. Inhibiting IDO with 1-DL-MT also had no effect on Trp degradation. In contrast, inhibiting TDO with 680C91 or LM10 significantly reduced Trp degradation. The expression of TDO but not of IDO correlated positively with Kyn accumulation in the HepG2 cell culture media. Furthermore, TDO degraded L-Trp but not D-Trp in HepG2 cells. Kyn is the main metabolite of Trp degradation by TDO in HepG2 cells. The accumulation of Kyn in HepG2 cells could be a key mechanism for tumor immune resistance. Two TDO inhibitors, 680C91 and LM10, could be useful in immunotherapy for liver cancers.

4.
J Med Case Rep ; 16(1): 233, 2022 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-35681144

RESUMEN

BACKGROUND: Coronavirus disease 2019 is an infectious disease with many presentations, and many of its effects on the human body are still unknown. Pheochromocytoma is a neuroendocrine tumor that may occur sporadically or be a manifestation of a hereditary disease line multiple endocrine neoplasia type 2. CASE PRESENTATION: In this study, we report a case of an Iranian patient infected with coronavirus disease 2019, causing unusual presentations of pheochromocytoma, including myocarditis and cerebrovascular involvement. CONCLUSIONS: We discovered a case of pheochromocytoma as an unusual presentation of COVID-19. In further investigations we also discovered thyroid medullary carcinoma and at the end MEN 2 syndrome was diagnosed. After proper treatment many symptoms were eliminated.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , COVID-19 , Neoplasia Endocrina Múltiple Tipo 2a , Feocromocitoma , Neoplasias de la Tiroides , Neoplasias de las Glándulas Suprarrenales/patología , Humanos , Irán , Neoplasia Endocrina Múltiple Tipo 2a/diagnóstico , Feocromocitoma/complicaciones , Feocromocitoma/diagnóstico , Feocromocitoma/patología , Neoplasias de la Tiroides/diagnóstico
5.
J Clin Med ; 11(5)2022 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-35268482

RESUMEN

Multiple factors influence graft rejection after kidney transplantation. Pre-operative factors affecting graft function and survival include donor and recipient characteristics such as age, gender, race, and immunologic compatibility. In addition, several peri- and post-operative parameters affect graft function and rejection, such as cold and warm ischemia times, and post-operative immunosuppressive treatment. Exposure to non-self-human leucocyte antigens (HLAs) prior to transplantation up-regulates the recipient's immune system. A higher rate of acute rejection is observed in transplant recipients with a history of pregnancies or significant exposure to blood products because these patients have higher panel reactive antibody (PRA) levels. Identifying these risk factors will help physicians to reduce the risk of allograft rejection, thereby promoting graft survival. In the current review, we summarize the existing literature on donor- and recipient-related risk factors of graft rejection and graft loss following kidney transplantation.

6.
Biomed Res Int ; 2022: 8949919, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-39281063

RESUMEN

Several factors have been reported to affect graft survival following kidney transplantation. CD52 molecules may increase T cell proliferation and activation, which may contribute to acute graft rejection and graft survival. In the current study, we studied the possible value of preoperative CD52 levels in predicting graft survival following renal transplantation. Ninety-six patients with end-stage renal disease who had kidney transplantation were included in the study from our prospective cohort. Blood samples were taken one day before surgery, and plasma CD52 levels were measured using ELISA (Cloud-Clone Corp., Houston, TX, USA). Acute rejection, acute tubular necrosis, delayed graft function, graft loss, BK infection, cytomegalovirus infection, and graft survival were evaluated. The mean age of recipients was 50.08 ± 12.82 years, and 64.6% were male. The incidence of delayed graft function, acute rejection, graft loss (p < 0.01), BK virus infection, and serum creatinine levels were significantly higher in recipients with high preoperative CD52 levels six months after transplantation (p < 0.05). Kaplan-Meier analysis revealed that three-year graft survival was significantly higher in patients with low preoperative CD52 levels (p < 0.0001). Univariate and multivariate Cox regression analyses showed that serum creatinine levels (hazard ratio [HR] = 1.7, p < 0.05), acute rejection (HR = 2.919, p < 0.05), and preoperative CD52 levels (HR = 3.114, p < 0.05) were independent prognostic factors for graft survival after kidney transplantation. We showed that high preoperative CD52 levels are associated with higher rates of acute rejection, delayed graft function, and BK virus infection and lower rates of graft survival after kidney transplantation.

7.
Clin Rheumatol ; 40(10): 4309-4315, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34052904

RESUMEN

BACKGROUND AND OBJECTIVE: Patients with rheumatic disease taking long-term disease-modifying anti-rheumatic drugs (DMARDs) are expected to have a higher risk of infection due to the alterations in cellular immunity associated with these medications. However, the potential risks associated with these drugs remain unclear. This study aimed to estimate the risk of COVID-19 infection in patients with rheumatic disease taking disease-modifying anti-rheumatic drugs. METHODS: Patients with autoimmune rheumatic disease taking DMARDs with or without long-term (> 6 months) HCQ treatment prior to the COVID-19 outbreak were selected consecutively. The diagnosis of COVID-19 was made based on the history of symptoms suggestive of the disease and/or serum IgG positivity. During statistical analysis, the risk of COVID-19 infection was calculated in rheumatic patients taking DMARDs versus controls, as well as in patients taking HCQ versus those who are not. The ORs and 95% CIs were also calculated. The participants in the control group were selected from individuals without RD. RESULTS: A total of 800 patients with RD and 449 controls were analyzed. COVID-19 infection was detected in 16.8% of rheumatic patients versus 17.6% of controls (OR 0.95; 95% CI 0.7-1.28). The proportions of COVID-19 infection in HCQ users versus non-users were 15.3% and 18.1%, respectively (OR 0.87; 95% CI 0.61-1.26). These results remained unchanged after adjusting for all covariates using logistic regression analysis. CONCLUSION: These findings indicate that rheumatic patients taking DMARDs are not at a higher risk of COVID-19 infection, and that HCQ therapy has no influence on the risk of COVID-19 infection. Key points • The risk of COVID-19 infection is not higher in patients with RD on DMARD therapy. • The prevalence of COVID-19 infection in HCQ users has not significant difference relative to non-users. • Significant percent of RD patients taking DMARDs had asymptomatic infection. • There was a positive association between leflunamide therapy and the risk of COVID-19 infection.


Asunto(s)
Antirreumáticos , COVID-19 , Enfermedades Reumáticas , Antirreumáticos/efectos adversos , Humanos , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/tratamiento farmacológico , SARS-CoV-2
8.
J Invest Surg ; 33(2): 141-146, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30335532

RESUMEN

Background: Experimental animal research has been pivotal in developing clinical kidney transplantation (KTx). One donor-associated risk factor with negative affect of transplantation outcome is brain death (BD). Many rat models for BD and KTx have been developed in the last decade, but no surgical guidelines have been developed for these models. Here, we describe a surgical technique for BD induction and the cuff technique for experimental KTx in rats.Methods: After intubation and mechanically ventilation of sixteen healthy adult male Sprague-Dawley rats were induction of BD performed. Animals were kept hemodynamically stable for eight hours. Then, the kidney was prepared and perfused with standard histidine-tryptophan-ketoglutarate solution. After explantation, grafts were immediately implanted in recipients using the cuff technique and reperfused. After 2 h of observation, animals were sacrificed by intravenous administration of potassium chloride.Results: In the early phase of BD, heart rate increased and mean arterial pressure decreased. Partial variations were observed in O2 partial pressure, O2 saturation, and HCO3. During the 2-h observation phase, all transplanted kidneys were sufficiently perfused macroscopically. There was no hyperacute rejection.Conclusions: It is feasible to observe BD for 8 h with maintained circulation in small experimental settings. The cuff technique for KTx is simple, the complication rate is low, and the warm ischemia time is short, therefore, this could be a suitable technique for KTx in the rat model.


Asunto(s)
Muerte Encefálica/inmunología , Modelos Animales de Enfermedad , Trasplante de Riñón/educación , Recolección de Tejidos y Órganos/educación , Animales , Estudios de Factibilidad , Rechazo de Injerto/epidemiología , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/inmunología , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Masculino , Ratas , Ratas Sprague-Dawley , Factores de Riesgo , Factores de Tiempo , Recolección de Tejidos y Órganos/efectos adversos , Recolección de Tejidos y Órganos/métodos
9.
Medicine (Baltimore) ; 98(37): e17006, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31517819

RESUMEN

CD200 is an immunoglobulin superfamily membrane protein that binds to a myeloid cell-specific receptor and induces inhibitory signaling. The aim of this study was to investigate the role of CD200 and its receptor (CD200R1) on kidney transplant (KTx) outcome. In a collective of 125 kidney recipients (University hospital, Heidelberg, Germany), CD200 and CD200R1 concentrations were evaluated immediately before transplantation. Recipient baseline and clinical characteristics and KTx outcome, including acute rejection (AR), acute tubular necrosis, delayed graft function, cytomegalovirus (CMV) and human polyomaviridae (BK) virus infections, and graft loss were evaluated during the first post-transplant year. The association of CD200 and CD200R1 concentrations and CD200R1/CD200 ratios with the outcome of KTx was investigated for the first time in a clinical setting in a prospective cohort. There was a positive association between pre-transplant CD200R1 concentrations and CMV (re)activation (P = .041). Also, increased CD200R1 concentration was associated with a longer duration of CMV infection (P = .049). Both the frequency of AR and levels of creatinine (3 and 6 months after KTx) were significantly higher in patients with an increased CD200R1/CD200 ratio (median: 126 vs 78, P = .008). Increased pre-transplant CD200R1/CD200 ratios predict immunocompetence and risk of AR, whereas high CD200R1 concentrations predict immunosuppression and high risk of severe CMV (re)activation after KTx.


Asunto(s)
Antígenos CD/sangre , Antígenos de Superficie/sangre , Fallo Renal Crónico/sangre , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Complicaciones Posoperatorias/diagnóstico , Receptores de Superficie Celular/sangre , Adulto , Anciano , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Receptores de Orexina , Periodo Preoperatorio , Pronóstico , Estudios Prospectivos , Adulto Joven
10.
Rev Med Virol ; 29(4): e2048, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31265195

RESUMEN

Seropositivity for HSV reaches more than 70% within the world population, and yet no approved vaccine exists. While HSV1 is responsible for keratitis, encephalitis, and labialis, HSV2 carriers have a high susceptibility to other STD infections, such as HIV. Induction of antiviral innate immune responses upon infection depends on a family of pattern recognition receptors called Toll-like receptors (TLR). TLRs bridge innate and adaptive immunity by sensing virus infection and activating antiviral immune responses. HSV adopts smart tricks to evade innate immunity and can also manipulate TLR signaling to evade the immune system or even confer destructive effects in favor of virus replication. Here, we review mechanisms by which HSV can trick TLR signaling to impair innate immunity. Then, we analyze the role of HSV-mediated molecular cues, in particular, NF-κB signaling, in promoting protective versus destructive effects of TLRs. Finally, TLR-based therapeutic opportunities with the goal of preventing or treating HSV infection will be discussed.


Asunto(s)
Terapia Biológica/métodos , Herpes Simple/inmunología , Herpes Simple/terapia , Inmunidad Innata , Simplexvirus/inmunología , Receptores Toll-Like/metabolismo , Interacciones Microbiota-Huesped , Humanos , Evasión Inmune , Simplexvirus/patogenicidad
11.
Ann Transplant ; 23: 393-400, 2018 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-29880786

RESUMEN

BACKGROUND The Model for End-Stage Liver Disease (MELD) score is a well-established tool for assessing hepatic failure. The present retrospective study investigated whether serum keratin 18 (M65) and caspase-cleaved cytokeratin (M30) were associated with liver dysfunction and post-transplant graft failure. MATERIAL AND METHODS A total of 147 patients with liver cirrhosis were categorized into 2 groups according to their baseline MELD score (group I: MELD score <20, n=87, and group II: MELD score ≥20, n=60). Serum M65 and M30 levels were measured by ELISA. RESULTS Cirrhotic patients had significantly higher serum M65 and M30 levels than healthy controls (p<0.0001). Serum M65 was correlated with the MELD score and serum bilirubin (p≤0.007) and serum M30 was correlated with the MELD score, international normalized ratio, and serum bilirubin (p≤0.001). Group II had significantly higher serum M65 and M30 levels than group I (M65, p=0.025 and M30, p<0.001). Patients who lost the allograft during the first post-transplant year had significantly higher serum M30 levels than patients with a graft survival of >1 year (p=0.004). In the regression analysis, serum M30 was associated with the MELD score (odds ratio [OR]=2.545, p=0.005), serum bilirubin (OR=2.605, p=0.005) and 1-year graft loss (OR=3.61, p=0.006). CONCLUSIONS Our data indicate that serum M30 levels reflect the degree of liver dysfunction and can predict 1-year graft loss.


Asunto(s)
Enfermedad Hepática en Estado Terminal/diagnóstico , Queratina-18/sangre , Trasplante de Hígado , Fragmentos de Péptidos/sangre , Adulto , Anciano , Enfermedad Hepática en Estado Terminal/sangre , Enfermedad Hepática en Estado Terminal/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
12.
Ann Transplant ; 23: 136-143, 2018 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-29472523

RESUMEN

BACKGROUND We evaluated whether effluent parameters prior to reperfusion correlate with post-transplant outcomes in liver transplant recipients. MATERIAL AND METHODS Concentrations of high mobility group box 1 protein (HMGB1), uncleaved cytokeratin-18 (M65), caspase-cleaved cytokeratin 18 fragment (M30), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP) were measured in effluent samples from 53 adult liver recipients (42 survived for 1 year and 11 did not survive). RESULTS Effluent concentrations of ALP (p=0.006), AST (p=0.050), and Ca++ (p=0.003) were higher in patients with bacteriemia in the first post-transplant year and ALP (p=0.015) was higher in patients with early graft dysfunction (EAD). Multivariate analysis of effluent parameters showed that Ca++ >0.30 mmol/l (p=0.012, odds ratio [OR]=7.12, confidence interval [CI]=1.56-32.58), and ALP ≥27 IU/l (p=0.033, OR=5.31, CI=1.14-27.74) were significantly associated with 1-year post-transplant bacteriemia, whereas ALP ≥27 IU/l (p=0.020, OR=5.56, CI=1.32-23.46) was significantly associated with EAD. HMGB1 >54 pg/ml (p=0.008, OR=6.05, CI=1.59-23.00) was significantly associated with the donor body mass index (p=0.008, OR=6.05, CI=1.59-23.00) and fatty liver (p=0.005, OR=11.68, CI=2.10-64.01). CONCLUSIONS Effluent parameters are indicators of liver quality and predict the outcome of liver transplantation. High effluent Ca++ and ALP are risk factors of post-transplant bacteriemia. In addition, high ALP is a risk factor of EAD, and high HMGB1 is an indicator of liver quality.


Asunto(s)
Índice de Masa Corporal , Trasplante de Hígado/mortalidad , Hígado/metabolismo , Receptores de Trasplantes , Adulto , Anciano , Alanina Transaminasa/metabolismo , Aspartato Aminotransferasas/metabolismo , Calcio/metabolismo , Femenino , Humanos , Donadores Vivos , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , gamma-Glutamiltransferasa/metabolismo
13.
Clin Transplant ; 31(12)2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28925558

RESUMEN

BACKGROUND: Non-HLA antibodies against human endothelial progenitor cells (EPC) in pre-transplant recipient serum can have a deleterious influence on the graft. EPC enriched from peripheral blood have been commonly used for EPC cross-matching. In the present study, we describe cross-matches using EPC enriched from fresh or frozen-thawed spleen cell preparations, thereby widening the sample source for deceased-donor cross-matching and retrospective studies. METHODS: EPC cross-matches were performed retrospectively using spleen cells and the flow cytometric XM-ONE cross-match test kit. RESULTS: Healthy controls (n = 28) showed no IgG antibodies against EPC. When sera of 11 random dialysis patients were studied, 2 patients (18%) exhibited IgG EPC antibodies. When pre-transplant sera of 20 kidney graft recipients with good long-term graft outcome (serum creatinine 1.0 ± 0.2 mg/dL measured 2463 ± 324 days post-transplant) were investigated using frozen-thawed and then separated Tie-2-enriched spleen cells of the original transplant donor, 3 patients (15%) had pre-transplant IgG EPC antibodies. When pre-transplant sera of 5 patients with intra-operative graft loss were studied employing the original donor spleen cells, 4 (80%) patients showed IgG EPC antibodies. CONCLUSIONS: Cross-matches with spleen cell-derived EPC using the XM-ONE assay are technically possible. Our very preliminary experience suggests clinical relevance.


Asunto(s)
Células Progenitoras Endoteliales/inmunología , Prueba de Histocompatibilidad , Isoanticuerpos/sangre , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Receptor TIE-2/metabolismo , Bazo/inmunología , Adulto , Anciano , Estudios de Casos y Controles , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Isoanticuerpos/inmunología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Bazo/citología , Bazo/metabolismo , Donantes de Tejidos , Receptores de Trasplantes
14.
Transpl Immunol ; 43-44: 21-26, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28716663

RESUMEN

BACKGROUND: Brain death (BD) is a donor-associated risk factor that negatively affects transplantation outcome. The inflammation associated with BD appears to have a negative effect on organ quality. Complement activation, apoptosis, and pro-inflammatory cytokine and chemokine expression are significantly increased after BD. To better understand this process, we investigated plasma chemokine and cytokine levels for 8h after BD in a rodent model. METHODS: Thirteen healthy adult male Sprague Dawley rats were intubated and mechanically ventilated. After induction of BD, animals were kept hemodynamically stable for 8h. A panel of immune response factors, including cytokines and chemokines, were measured immediately prior to the induction of BD and at 1, 4, and 8h after BD by multiplex analyses in 10 rats. RESULTS: In the early phase of BD, we observed an increase in heart rate and a decrease in mean arterial pressure. Only limited fluctuations were noted in the partial pressure of O2, O2 saturation, and HCO3. Monocyte-/macrophage- and lymphocyte-derived mediators (IL-2, IL-4, and IFN-γ) increased steadily during the 8-hour monitoring period. CONCLUSIONS: The increase in immune responses, particularly pro-inflammatory responses, after BD is time-dependent. Cytokines and chemokines from donors and recipients require further investigation to determine the optimal time frames for organ transplantation in rodent models and humans.


Asunto(s)
Muerte Encefálica , Quimiocinas , Mediadores de Inflamación , Animales , Muerte Encefálica/sangre , Muerte Encefálica/inmunología , Quimiocinas/sangre , Quimiocinas/inmunología , Modelos Animales de Enfermedad , Mediadores de Inflamación/sangre , Mediadores de Inflamación/inmunología , Trasplante de Órganos , Oxígeno/sangre , Oxígeno/inmunología , Ratas , Ratas Sprague-Dawley
15.
Caspian J Intern Med ; 8(1): 23-29, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28503279

RESUMEN

BACKGROUND: Cytomegalovirus (CMV) disease is an important cause of death and possibly transplant rejection in kidney transplant (KT) patients. This study was conducted to investigate the incidence and risk factors of CMV disease in kidney transplant patients. METHODS: All end-stage renal disease (ESRD) patients who underwent kidney transplantation during 1998-2014 and their donors were assessed. All samples were followed-up for approximately 70 months. CMV was identified by polymerase chain reaction (PCR) and/or PP65 antigen in peripheral blood leukocytes along with clinical manifestations. RESULTS: A total of 1450 cases participated in the current study. CMV was diagnosed in 178 out of 725 (24.6%) kidney recipients. The annual incidence of CMV disease was 4.2%. Patients older than 40 years had a higher incidence of CMV disease. The level of CMV disease incidence in the 41-60 age group was 4 fold compared to those under 20 of age group (P=0.001). CONCLUSION: This study demonstrated that the incidence of CMV disease in our region is relatively low and also age more than 40 years and EBV infection are the important risk factors in kidney transplant patients. So care and monitoring of these patients are crucial in the first 5 months.

16.
BMC Immunol ; 17(1): 35, 2016 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-27716059

RESUMEN

BACKGROUND: Cytomegalovirus seropositivity is an independent risk factor for atherosclerosis in patients with ESRD. Donor CMV seropositivity is associated with higher graft loss. Dendritic cells, macrophages and Th17 lymphocytes are defined as producers of IL-23. IL-23 is thought to be involved in the promotion of Th17 cell polarization. Latent CMV-induced Th17 might be involved in the pathogenesis of CMV infection in patients with ESRD. We aimed to evaluate associations of Th17-dependent cytokines with ESRD, CMV status and post-transplant outcome in kidney transplantation. RESULTS: IL-21 plasma levels were similar in patients and healthy controls (p = 0.47), whereas IL-9 (p = 0.02) and IL-23 (p < 0.0001) levels were significantly higher in ESRD patients. CMV-seronegative (p = 0.002) and -seropositive (p < 0.001) patients had significantly higher IL-23 plasma levels than controls. CMV-seropositive patients showed excessively higher IL-23 (p < 0.001) plasma levels than CMV-seronegative patients. Patients with post-transplant CMV reactivation had higher IL-23 plasma levels than patients without CMV reactivation (p = 0.025). CONCLUSIONS: Our results indicate that latent CMV induces IL-23. IL-23 might be an inflammatory mediator of latent CMV infection in patients with ESRD and predisposes patients for post-transplant CMV reactivation.


Asunto(s)
Biomarcadores/sangre , Infecciones por Citomegalovirus/inmunología , Citomegalovirus/inmunología , Células Dendríticas/inmunología , Rechazo de Injerto/inmunología , Interleucina-23/sangre , Trasplante de Riñón , Macrófagos/inmunología , Complicaciones Posoperatorias/inmunología , Células Th17/inmunología , Adulto , Anciano , Animales , Anticuerpos Antivirales/sangre , Femenino , Alemania , Humanos , Interleucinas/sangre , Masculino , Ratones , Persona de Mediana Edad , Trasplante Homólogo , Activación Viral
17.
Hum Immunol ; 77(10): 952-960, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27476050

RESUMEN

UNLABELLED: Early allograft dysfunction (EAD) after liver transplantation is mostly a reversible event caused by factors related to ischemia/reperfusion (I/R) injury. EAD represents a hepatic injury associated with pre- and early post-transplant inflammatory cytokine responses. Aim of the present study was to evaluate the prognostic and diagnostic value of CRP in liver transplant recipients with EAD. MATERIALS AND METHODS: Forty-seven patients with EAD were compared with 115 non-EAD patients. Pre- and post-transplant parameters were analyzed. EAD was defined based on postoperative liver function tests such as INR, bilirubin and liver enzymes. Statistical analysis was performed using SPSS version 18.0. RESULTS: Pre-transplant liver enzyme were not significantly different in the two groups. At day 3, 5 and 10 post-transplant CRP was significantly higher in patients with EAD than in non-EAD patients (p⩽0.001 for all investigations) and remained consistently high in patients with EAD and low in non-EAD patients. EAD patients with high CRP at post-transplant days 3 and 5 showed lower survival at 6-month and 12-month post-transplant than patients with low CRP. CONCLUSION: Our results indicate a prognostic and diagnostic value of CRP in patients with early graft dysfunction and predict 6-month and 12-month mortality in liver transplant recipients.


Asunto(s)
Reacción de Fase Aguda/diagnóstico , Proteína C-Reactiva/metabolismo , Funcionamiento Retardado del Injerto/diagnóstico , Trasplante de Hígado , Análisis de Supervivencia , Reacción de Fase Aguda/etiología , Reacción de Fase Aguda/mortalidad , Adulto , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Bilirrubina/sangre , Funcionamiento Retardado del Injerto/etiología , Funcionamiento Retardado del Injerto/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico
18.
Clin Transplant ; 30(2): 124-30, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26537026

RESUMEN

BACKGROUND: Literature reports suggest that non-HLA-antibodies against human endothelial progenitor cells (EPC) can be detected in pre-transplant recipient serum and that EPC antibodies can have a deleterious influence on the graft. METHODS: We investigated 71 renal transplant recipients from living donors for a possible influence of pre-transplant donor-specific IgG and/or IgM recipient antibodies against EPC of the donor using the flow cytometric XM-ONE cross-match. RESULTS: Eight of the 71 patients developed acute biopsy-proven rejection. Two of these patients showed IgM antibodies against EPC prior to transplantation while the other six patients had neither IgG nor IgM EPC antibodies. Conversely, pre-transplant IgG or IgM antibodies against EPC were detected in 19 patients without acute rejection (3 × both IgG and IgM, 1 × IgG and 15 × IgM). The remaining 44 patients had neither EPC antibodies nor experienced rejection. Comparing serum creatinine levels at one month and one yr post-transplant within and among the three patient groups revealed that serum creatinine levels were similar in patients with or without EPC antibodies (p > 0.05). CONCLUSION: In this series of 71 recipients with living donor kidneys, pre-transplant EPC antibodies detected with the XM-ONE test kit were neither associated with acute rejection nor with graft function at one month or one yr.


Asunto(s)
Células Progenitoras Endoteliales/inmunología , Rechazo de Injerto/diagnóstico , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Isoanticuerpos/sangre , Trasplante de Riñón , Donadores Vivos , Adulto , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/epidemiología , Rechazo de Injerto/etiología , Supervivencia de Injerto , Prueba de Histocompatibilidad , Humanos , Isoanticuerpos/inmunología , Fallo Renal Crónico/cirugía , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , Factores de Riesgo , Receptores de Trasplantes
19.
Hum Immunol ; 77(1): 115-120, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26582003

RESUMEN

Bacterial infections are the most common complications, and the major cause of mortality after liver transplantation (Tx). Neopterin, a marker of immune activation, is produced in monocyte/macrophages in response to inflammation. The aim of our study was to investigate whether early post-operation serum levels of neopterin were associated with post-transplant bacteremia and mortality in liver transplant recipients. We studied 162 of 262 liver Tx patients between January 2008 and February 2011 of whom pre- and early post-Tx sera samples were available. Pre- and early post-operative risk factors of infection and mortality were evaluated in 45 bacteremic patients and 117 non-bacteremic patients. During one-year follow-up, 28 of 262 patients died because of graft failure, septicemia and other diseases. Post-Tx serum neopterin on day 10 (p<0.001) were significantly higher in bacteriemic patients than in patients without bacteremia. Logistic regression analyses showed that day 10 post-Tx neopterin serum level ⩾40 nmol/l has a predictive value (OR=6.86: p<0.001) for bacteremia and mortality (OR=3.47: p=0.021). Our results suggest that early post-Tx neopterin serum levels are very sensitive predictive markers of one-year post-Tx bacteremia and mortality in liver Tx recipients.


Asunto(s)
Bacteriemia/diagnóstico , Biomarcadores/sangre , Inflamación/diagnóstico , Trasplante de Hígado , Neopterin/sangre , Adulto , Bacteriemia/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Inflamación/mortalidad , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Sensibilidad y Especificidad , Análisis de Supervivencia
20.
Caspian J Intern Med ; 6(4): 209-12, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26644894

RESUMEN

BACKGROUND: Serial measurement of hepatitis B virus (HBV) DNA levels in the liver and its relation with liver damage and serum HBV DNA levels are guide to begin and/or end a treatment course. This study evaluated the relationship between liver hepatitis B DNA viral load with liver histology in patients with chronic hepatitis B (HBV). METHODS: Thirty patients with chronic anti-Hbe positive hepatitis B, with liver enzymes ≥ 2 times of the upper limit of normal and positive HBV DNA of any amount were entered in the study. They underwent percutaneous liver biopsy. Liver and serum viral load were determined using real time polymerase chain reaction method (RT-PCR). Liver function tests and liver histology for all cases were recorded. The amount of viral load in the liver and histological grading and staging were recorded. Data were collected and analyzed. RESULTS: The mean age of the patients was 32.8±10 years and 24 (80%) patients were males. Ten (33.3%) patients had HBV viral load levels less than 20000 IU/mL. There was a significant correlation between liver viral load levels with staging or grading of liver damage. CONCLUSION: The results of the present study showed a strong correlation between liver viral load and liver damage in patients with chronic hepatitis B.

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