A high level of urinary retinol-binding protein is associated with cytomegalovirus infection in kidney transplantation.

The indirect effects of cytomegalovirus (CMV) viremia can be related to chronic changes in renal allograft structure, but its real impact in early and late graft function remains speculative. A total of 159 patients undergoing renal transplantation using a preemptive therapeutic strategy to prevent CMV disease were included in the present study. The patients were prospectively followed, with serial measurements of urinary retinol-binding protein (uRBP), a marker of proximal tubule injury. uRBP levels and their dynamic performance were compared according to CMV viremia and the 5-year estimated glomerular filtration rate (eGFR), as measured with the modification of diet in renal disease (MDRD) equation. CMV viremia was detected in 79.9% of the patients, with high uRBP levels being detected in 76.0% of these patients (compared with 40.7% in CMV-, P=0.005). High uRBP was associated with male recipients (P=0.02), the number of mismatches (P=0.02) and CMV infection (P=0.001). Five-year eGFR was worse in patients with high uRBP levels (50.3 ± 25.8 compared with 59.8 ± 26.4 ml/min, P=0.04). In a multivariate model, eGFR <60 ml/min was associated with donor age (P<0.001), the number of mismatches (P=0.04), thymoglobulin dose (P=0.02), the presence of and time with delayed graft function (DGF) (P=0.005 and P=0.04), 1-month tacrolimus levels (P=0.03), and uRBP levels after CMV treatment (P=0.01). Patients with CMV viremia in whom uRBP levels were normalized up to 3 months after treatment showed significantly better 5-year eGFR than those in whom uRBP remained high: 61.0 ± 24.2 compared with 42.3 ± 23.9 ml/min, P<0.001. CMV viremia was associated with high uRBP levels, which represent a profile of proximal tubule injury, and the dynamic performance of uRBP after treatment was associated with long-term kidney graft function.

Contribution of alloantigens to hepatic ischemia/reperfusion injury: Roles of natural killer cells and innate immune recognition of nonself.

Hepatic ischemia/reperfusion injury (IRI) remains a major clinical problem and involves the innate immune system's recognition of "nonself." Considering the efficient nonself recognition by natural killer (NK) cells, we hypothesize in this study that hepatic IRI associated with liver transplantation (LT) could be augmented in allogeneic rather than in syngeneic (Syn) grafts due to alloantigen recognition by innate immune cells, especially by NK cells. Using green fluorescent protein (GFP)/Sprague-Dawley rats, we tested our hypothesis in a rat LT model with 18 hours of cold storage in University of Wisconsin solution. Hepatic IRI was significantly augmented in allografts with higher alanine transaminase levels, increased necrosis, and vigorous proinflammatory mediator up-regulation compared to Syn grafts. Injury increased in allografts associated with augmented GFP+ host leukocyte infiltration due to significantly increased host CD11b/c+ and RP-1(+) neutrophil recruitment. A large number of liver-resident (donor) mature CD11b/c+ NK cells quickly diminished from allografts, but not from Syn grafts. Depletion of mature NK cells from liver grafts with anti-asialo monosialotetrahexosylganglioside significantly improved hepatic IRI and reduced neutrophil infiltration and proinflammatory mediators. In conclusion, early innate immune responses were more significantly enhanced in allografts than in Syn grafts during hepatic IRI, in part through NK cell recognition of "missing self."

Roles of dendritic cells in murine hepatic warm and liver transplantation-induced cold ischemia/reperfusion injury.

UNLABELLED: Dendritic cells (DCs) induce and regulate both innate and adaptive immune responses; however, their in vivo functional importance in hepatic ischemia/reperfusion (IR) injury is perplexing. We hypothesized that liver-resident DC and locally recruited blood-borne DC might have distinctive roles in hepatic IR injury. We tested this hypothesis by using DC-deficient, fms-like tyrosine kinase 3 ligand (Flt3L) knockout (KO) mice in hepatic warm (70% partial clamping for 60 minutes) and cold IR injury (liver transplant [LTx] with 24-hour cold storage). Flt3L KO liver and lymphoid organs contained virtually no CD11c+ F4/80- DC. Hepatic warm IR injury was significantly lower in Flt3L KO than in wildtype (WT) mice with lower alanine aminotransferase (ALT) levels, reduced hepatic necrosis, and lower neutrophil infiltration. Hepatic messenger RNA (mRNA) and protein levels for inflammatory cytokines (tumor necrosis factor alpha [TNFα], interleukin [IL]-6) and chemokines (CCL2, CXCL2) were also significantly lower in Flt3L KO than in WT mice, indicating that lack of both liver-resident and blood-borne DC ameliorated hepatic warm IR injury. Adoptive transfer of splenic or hepatic WT DC into Flt3L KO or WT mice increased hepatic warm IR injury, suggesting injurious roles of DC infusion. When Flt3L KO liver was transplanted into WT mice, ALT levels were significantly higher than in WT to WT LTx, with enhanced hepatic necrosis and neutrophil infiltration, indicating a protective role of liver-resident DC. CONCLUSION: Using both warm and cold hepatic IR models, this study suggests differential roles of liver-resident versus blood-borne DC, and points to the importance of the local microenvironment in determining DC function during hepatic IR injury.

The loss of renal dendritic cells and activation of host adaptive immunity are long-term effects of ischemia/reperfusion injury following syngeneic kidney transplantation.

Ischemia/reperfusion injury associated with kidney transplantation induces profound acute injury, influences early graft function, and affects long-term graft outcomes. To determine whether renal dendritic cells play any role during initial innate ischemia/reperfusion injury and the subsequent development of adaptive immune responses, we studied the behavior and function of renal graft and host infiltrating dendritic cells during early and late phases of renal ischemia/reperfusion injury. Wild type to green fluorescent protein (GFP) transgenic rat kidney transplantation was performed with and without 24-h cold storage. Ischemia/reperfusion injury in cold-stored grafts resulted in histopathological changes of interstitial fibrosis and tubular atrophy by 10 weeks, accompanied by upregulation of mRNAs of mediators of interstitial fibrosis and inflammation. In normal rat kidneys, we identified two populations of renal dendritic cells, predominant CD103(-)CD11b/c(+) and minor CD103(+)CD11b/c(+) cells. After transplantation without cold storage, grafts maintained CD103(-) but not CD103(+) GFP-negative renal dendritic cells for 10 weeks. In contrast, both cell subsets disappeared from cold-stored grafts, which associated with a significant GFP-expressing host CD11b/c(+) cell infiltration that included CD103(+) dendritic cells with a TNF-α-producing phenotype. These changes in graft/host dendritic cell populations were associated with progressive infiltration of host CD4(+) T cells with effector/effector-memory phenotypes and IFN-γ secretion. Thus, renal graft ischemia/reperfusion injury caused graft dendritic cell loss and was associated with progressive host dendritic cell and T-cell recruitment. Renal-resident dendritic cells might function as a protective regulatory network.

Carbon monoxide inhibits apoptosis during cold storage and protects kidney grafts donated after cardiac death.

Ischemia/reperfusion (I/R) injury remains as a serious deleterious factor in kidney transplantation (KTx). We hypothesized that carbon monoxide (CO), an endogenous potent cytoprotective molecule, inhibits hypothermia-induced apoptosis of kidney grafts. Using the rat KTx model mimicking the conditions of donation after cardiac death (DCD) as well as nontransplantable human kidney grafts, this study examined effects of CO in preservation solution in improving the quality of marginal kidney grafts. After cardiac cessation, rat kidneys underwent 40 min warm ischemia (WI) and 24 h cold storage (CS) in control UW or UW containing CO (CO-UW). At the end of CS, kidney grafts in control UW markedly increased mitochondrial porin release into the cytosol and resulted in increased cleaved caspase-3 and PARP expression. In contrast, grafts in CO-UW had significantly reduced mitochondrial breakdown and caspase pathway activation. After KTx, recipient survival significantly improved with CO-UW with less TUNEL(+) cells and reduced mRNA upregulation for proinflammatory mediators (IL-6, TNF-α, iNOS). Furthermore, when nontransplantable human kidney grafts were stored in CO-UW for 24 h, graft PARP expression, TUNEL(+) cells, and proinflammatory mediators were less than those in control UW. CO in UW inhibited hypothermia-induced apoptosis and significantly improved kidney graft function and outcomes of KTx.

Use of carbon monoxide in minimizing ischemia/reperfusion injury in transplantation.

Although carbon monoxide (CO) is known to be toxic because of its ability to interfere with oxygen delivery at high concentrations, mammalian cells endogenously generate CO primarily via the catalysis of heme by heme oxygenases. Recent findings have indicated that heme oxygenases and generation of CO serve as a key mechanism to maintain the integrity of the physiological function of organs and supported the development of a new paradigm that CO, at low concentrations, functions as a signaling molecule in the body and exerts significant cytoprotection. Consequently, exogenously delivered CO has been shown to mediate potent protection in various injury models through its anti-inflammatory, vasodilating, and antiapoptotic functions. Ischemia/reperfusion (I/R) injury associated with organ transplantation is one of the major deleterious factors limiting the success of transplantation. Ischemia/reperfusion injury is a complex cascade of interconnected events involving cell damage, apoptosis, vigorous inflammatory responses, microcirculation disturbance, and thrombogenesis. Carbon monoxide has a great potential in minimizing I/R injury. This review will provide an overview of the basic physiology of CO, preclinical studies examining efficacy of CO in I/R injury models, and possible protective mechanisms. Carbon monoxide could be developed to be a valuable therapeutic molecule in minimizing I/R injury in transplantation.

Hepatic B7 homolog 1 expression is essential for controlling cold ischemia/reperfusion injury after mouse liver transplantation.

UNLABELLED: Ischemia/reperfusion (I/R) injury remains a key risk factor significantly affecting morbidity and mortality after liver transplantation (LT). B7 homolog 1 (B7-H1), a recently identified member of the B7 family, is known to play important roles in regulating local immune responses. We hypothesized that B7-H1 plays crucial roles during innate immune responses induced by hepatic I/R injury, and using B7-H1 knockout (KO) liver grafts, we tested this hypothesis in the mouse LT model with 24 hours of cold storage. Cold I/R injury in wild type (WT)-to-WT LT enhanced constitutive B7-H1 expression on dendritic cells and sinusoidal endothelial cells and promptly induced B7-H1 on hepatocytes. When B7-H1 KO liver grafts were transplanted into WT recipients, serum alanine aminotransferase (ALT) and graft necrosis levels were significantly higher than those after WT-to-WT LT. Augmented tissue injury in B7-H1 KO grafts was associated with increased frequencies and absolute numbers of graft CD3(+) T cells (particularly CD8(+) T cells). B7-H1 KO grafts had significantly fewer annexin V(+) CD8(+) T cells, and this indicated a failure to delete infiltrating CD8(+) T cells. To evaluate the relative contributions of parenchymal cell and bone marrow-derived cell (BMDC) B7-H1 expression, we generated and transplanted into WT recipients chimeric liver grafts lacking B7-H1 on parenchymal cells or BMDCs. A selective B7-H1 deficiency on parenchymal cells or BMDCs resulted in similar levels of ALT and liver injury, and this suggested that parenchymal cell and BMDC B7-H1 expression was involved in liver damage control. Human livers up-regulated B7-H1 expression after LT. CONCLUSION: The study demonstrates that graft tissue expression of B7-H1 plays a critical role in regulating inflammatory responses during LT-induced hepatic I/R injury, and negative coregulatory signals may have an important function in hepatic innate immune responses.

Expression of TLR-4 and -2 in peripheral mononuclear cells in renal transplant patients with TLR-4 gene polymorphism.

INTRODUCTION: TLR-4 has also been identified as a receptor for endogenous alarmins, which are increased post transplantation. TLR-4 has also been associated with a polymorphism that could impact graft outcome. OBJECTIVE: To assess the expression of TLR-4 in kidney transplant patients carrying or not a polymorphism. METHODS: TLR-4 polymorphism (A299G/T399I) was studied in 200 renal transplant patients. Healthy volunteers were also enrolled as control group. The polymorphism analysis was performed using restriction enzymes technique (RFLP). Functionality of TLR-4 polymorphism was assessed in samples from controls by quantification of TNF-α after LPS stimulus. TLR-4 and -2 expressions were also analyzed by flow cytometry. RESULTS: TLR-4 polymorphism was present in 8.5% of renal transplant patients. This polymorphism was associated with impairment in TNF-α secretion. In general, in renal transplant patients, TLR-4 expression in monocytes and in neutrophils was lower than in health volunteers. TLR-2 and TLR-4 expressions in healthy volunteers with A299G/T399I TLR-4 polymorphism was higher than in wild-type genotype healthy volunteers (p<0.01 and p<0.05, respectively), and also higher than A299G/T399I TLR-4 polymorphism renal transplant patients (p<0.05). TLR-2 expression on neutrophils in wild-type genotype renal transplant patients was higher compared to wild-type genotype healthy volunteers, and was also higher in relation to A299G/T399I kidney transplanted patients (p<0.01). CONCLUSION: Stable renal transplant patients with TLR-4 polymorphism have a lower expression of TLR-4 and TLR-2 receptors in peripheral mononuclear cells, which ultimately indicate a less responsiveness for alarmins.

Critical role of interferon regulatory factor-1 in murine liver transplant ischemia reperfusion injury.

Interferon regulatory factor-1 (IRF-1) is a transcription factor that regulates gene expression during immunity. We hypothesized that IRF-1 plays a pivotal role in liver transplant (LTx) ischemia/reperfusion (I/R) injury. Mouse orthotopic LTx was conducted after 24 hours cold storage in University of Wisconsin (UW) solution in wildtype (WT) C57BL/6 and IRF-1 knockout (KO) mice. IRF-1 deficiency in liver grafts, but not in recipients, resulted in significant reduction of hepatocyte apoptosis and liver injury, as well as improved survival. IRF-1 mRNA up-regulation was typically seen in graft hepatocytes in WT-->WT LTx. Deficiency of IRF-1 signaling in graft resulted in significantly reduced messenger RNA (mRNA) levels for death ligands and death receptors in hepatocytes, as well as decreased caspase-8 activities, indicating that IRF-1 mediates death ligand-induced hepatocyte death. Further, a smaller but significant IRF-1 mRNA up-regulation was seen in WT graft nonparenchymal cells (NPC) and associated with interferon gamma (IFN-gamma) mRNA up-regulation exclusively in NPC. IFN-gamma mRNA was significantly reduced in IRF-1 KO graft. Thus, IRF-1 in graft hepatocytes and NPC has distinct effects in hepatic I/R injury. However, LTx with chimeric liver grafts showed that grafts lacking hepatocellular IRF-1 had better protection compared with those lacking IRF-1 in NPC. The study identifies a critical role for IRF-1 in liver transplant I/R injury.

Clinical correlations of human cytomegalovirus strains and viral load in kidney transplant recipients.

Little is known about clinical differences associated with cytomegalovirus (CMV) infection by distinct strains in renal transplant patients. Different clinical pictures may be associated with specific viral genotypes, viral load, as well as host factors. The objective of this study was to identify CMV strains to determine viral load (antigenemia), and their correlation with clinical data in renal transplant recipients. Seventy-one patients were enrolled, comprising 91 samples. After selection, polymorphonuclear cells were used to amplify and sequence the gB region of CMV DNA. The sequences were analyzed to ascertain the frequency of different genotypes. Additionally, the results of this study showed that the gB coding gene presents a great variability, revealing a variety of patterns: classical gB1 (1.4%), gB1V (46.4%), classical gB2 (35.2%), gB2V (2.8%), gB3 (1.4%), classical gB4 (4.9%) and gB4V (4.9%). The mean viral load in kidney transplant patient was 75.1 positive cells (1-1000). A higher viral load was observed in patients with genotype 4 infection. Statistically significant differences were detected between gB1 and gB4 (p=0.010), and between gB2 and gB4 (p=0.021). The average numbers of positive cells in relation to clinical presentation were: 34.5 in asymptomatic, 49.5 in CMV associated syndrome and 120.7 in patients with invasive disease (p=0.048). As a group, gB1 was the most frequent strain and revealed a potential risk for developing invasive disease. Viral load also seemed to be important as a marker associated with clinical presentation of the disease.

The use of sirolimus in ganciclovir-resistant cytomegalovirus infections in renal transplant recipients.

BACKGROUND: The widespread use of prophylactic ganciclovir and anti-lymphocyte/thymocyte therapies are associated with increased induction of ganciclovir-resistant cytomegalovirus (CMV) strains. The use of sirolimus has been associated with a lower incidence of CMV infection in transplant recipients. We questioned whether it could also be effective as a therapeutic treatment of resistant CMV infection. METHODS: Patients with ganciclovir-resistant CMV infections determined clinically and by DNA sequencing analysis were enrolled. Antigenaemia and DNA sequencing were used to diagnosis and follow the mutations. RESULTS: Nine transplant patients were given sirolimus plus mycophenolate mofetil (n = 4) or a calcineurin inhibitor (n = 5). Seven out of nine recipients were CMV IgG negative before transplantation. We observed a rapid decrease in antigenaemia levels, reaching zero in eight out of nine (88.9%) patients within a median of 20.3 +/- 10.1 d. Graft function remained stable and no patient presented acute rejection or recurrence of the CMV infection. CONCLUSIONS: This suggests that the use of sirolimus plus ganciclovir therapy could be useful in ganciclovir-resistant CMV infections.

Pregnancy after renal transplantation--a five-yr single-center experience.

BACKGROUND: There has been an increase in the number of pregnancies in renal transplant recipients. Our aim was to report our experience with a significant casuistic. METHODS: Fifty-two pregnancies in 52 patients (January 2001 to December 2005), with two patients having a multiple pregnancy, were evaluated and patients were characterized and evaluated as clinical and obstetrical and perinatal outcomes. RESULTS: Mean patient age was 26.5 yr (range 17-38) with live donors in 34 (65.4%) and cadaver donors in 18 (34.6%). The mean transplantation-pregnancy interval was 3.1 yr. Calcineurin inhibitors (cyclosporine or tacrolimus) comprised the immunosuppressive therapy in 49 pregnancies (94.2%). Pregnancy complications were chronic hypertension in 33 patients (63.5%), anemia in 31 (59.6%), urinary tract infection in 22 (42.3%) and diabetes in four (7.7%). Nine patients (17.3%) received blood transfusion. Preeclampsia was diagnosed in 16 cases (30.7%) and renal dysfunction in 23 (44.2%) with preeclampsia assumed to be the main cause. One patient (1.9%) had graft loss, as a result of hemorrhagic shock after preterm delivery at home. Premature rupture of membranes occurred in four cases (7.7%), and preterm delivery in 20 (38.4%). Sixteen (29.6%) newborn were small for gestational age. One case of neonatal death was registered as a result of excessive prematurity. Cesarean section was performed in 32 patients (61.5%), the main indications being related to hypertension syndromes and fetal distress. CONCLUSIONS: This group of patients is characterized by a wide range of antenatal and perinatal problems and must be managed in specialized tertiary units to achieve the very best results.

Prognostic factors associated with poor graft outcomes in renal recipients with post-transplant glomerulonephritis.

BACKGROUND: Little data are available concerning post-transplantation glomerulonephritis (PTx-GN) and its prognostic factors associated with graft outcomes. METHODS: We retrospectively evaluated patients with de novo and recurrent PTx-GN to identify the factors associated with their negative impact on graft and patient outcomes. PTx-GN was diagnosed in 55 patients, wherein 17 (31%) had recurrent glomerulonephritis (GN) and 16 (29%) had de novo. RESULTS: Our enrolled population consisted of 34 +/- 13.7-yr-old male patients (72%), on hemodialysis for a median of 18 months (0-204) and mainly grafted from living donors (76%). The median onset time of proteinuria and hematuria was 50 d (10-2160) and 30 d (4-1170), respectively. One-yr graft survival rates after PTx-GN diagnosis was 64%. The most frequent de novo GN was membranous GN (26%), while focal segmental glomerulosclerosis was the most frequent recurrent GN (41%), with a very early onset (median of three months). One-yr graft survival was better in the recurrent disease than in the de novo patients, 76% vs. 55% (p = 0.24). The best predictor factors that correlated with graft survival were: proteinuria <3.5 g [relative risk (RR) = 0.24, p = 0.017], serum creatinine below 2.0 mg/dL (RR = 0.06, p = 0.016) at the time of biopsy and the use of angiotensin-converting enzyme inhibitors (ACEI) (RR = 0.12, p = 0.005). The use of ACEI markedly improved one-yr graft survival rates (92% vs. 47%, p < 0.001). CONCLUSION: PTx-GN has a strong negative impact on kidney graft survival. De novo GN appears to have a poorer prognosis than the recurrent type. Patients who used ACEI showed a better survival rate in the follow-up.

The emergence of cytomegalovirus resistance to ganciclovir therapy in kidney transplant recipients.

Transplant recipients that have not been previously exposed to the cytomegalovirus (CMV) are highly susceptible to viral diseases while under immunosuppression therapy. CMV disease requires prolonged therapy, facilitating the emergence of resistant strains. Persistence of positive antigenemia represents clinical evidence of the presence of resistant strains, although its frequency is unknown. These strains may present amino acid deletions or substitutions in conserved regions of the UL97 protein, point mutations in the DNA polymerase (UL54), or both. In this study we aimed to analyze the prevalence of mutations associated with ganciclovir resistance in transplant recipients. Fifteen kidney transplant recipients and four kidney-pancreas transplant recipients, with a positive and oscillating CMV viremia detected by sequential antigenemia test, were enrolled. The UL97 gene was amplified by Nested-PCR and enzymatically digested in samples of these patients in order to detect mutations in the most common codons, such as 460 (M460V), 594 (A594V) and 595(L595S/F). The end-product fragments were further sequenced. Nine (47.4%) out of 19 patients presented with mutations in UL97 at codons L595S (55.6%), A594V (11.1%), A595F/A594V (11.1%) and L595S/A594V (22.2%). None presented with mutation at the M460V codon. Renal transplant patients with oscillation in viral load for more than 2 weeks might have developed viral resistance to anti-drug therapy. Its detection might aid physicians in their clinical plan of tapering the patient's immunosuppression.

Frequency of Valpha24+Vbeta11+ NKT cells in peripheral blood of human kidney transplantation recipients.

There are still lacking data supporting a role for natural killer T (NKT) cells in the maintenance of human tissue-specific tolerance. We are interested to study NKT cell frequency in kidney transplant recipients and its correlation with graft function. Peripheral blood T cell receptors (TCR) Valpha24(+)Vbeta11(+) NKT cells were phenotyped according to CD4 and CD8 expression in normal controls (NC), in 10 years rejection-free cadaver kidney allografts maintained with minimal immunosuppression (long-term rejection free [LTRF]), in patients with acute rejection (AR) and in patients with acute tubular necrosis (ATN). Results were expressed as percentages of CD4(+)CD8(-) (CD4(+) NKT) or CD4(-)CD8(-) (double negative--DN NKT) Valpha24(+)Vbeta11(+) cells. The percentages of Valpha24(+)Vbeta11(+) cells were 0.09%, 0.14%, 0.02% and 0.09% on gated lymphocytes respectively in AR, ATN, LTRF and NC groups (p=0.263). DN NKT cells were more frequent in NC patients (52.11%) and less present in ATN patients (11.04%). In contrast, CD4(+) NKT (IL-4-producing NKT cells subset) was more frequent in AR (42.86%), and corresponded to almost 3 to 7 folds more what we obtained in the other groups. Although total Valpha24(+)Vbeta11(+) cells did not significantly differ among the groups, the lowest frequency was observed in the LTRF group. In conclusion, we observed that total number of NKT cells did not differ significantly among transplant patients when compared to normal controls, although specific-subsets seem to be more frequent in determined events.

Decreased Cytomegalovirus infection after antilymphocyte therapy in sirolimus-treated renal transplant patients.

Cytomegalovirus (CMV) infection is highly prevalent in transplant patients, especially in those submitted to a more intense immunosuppression. We monitored CMV infection in 34 patients during 60 days after antilymphocyte therapy without CMV prophylaxis. Six patients received sirolimus and 28 received no sirolimus as immunosuppression. During 60 days of follow-up time, 24/28 (86%) patients who did not use sirolimus developed CMV infection at a mean time of 32.43+/-13.67 days after antilymphocyte treatment. In contrast, no patient on sirolimus had CMV infection during the same follow-up (p<0.001). During a further 4-month follow-up, six patients on sirolimus-free therapy had recurrence of CMV, 46.5+/-18.5 days after the first episode. During this same period, one patient receiving sirolimus had one positive cell for CMV antigenemia, 169 days after antilymphocyte therapy. In conclusion, the use of sirolimus significantly reduced the incidence of CMV infection in patients treated with antilymphocyte antibodies.

Efeito da vacina contra hepatite B em indivíduos com anticorpos contra o antígeno central da hepatite B (anti-HBc) como único mercador / Effect of the hepatitis B vaccine in indididuals with antibodies against the central antigen of hepatitis B virus as the sole marker

Indivíduos repetidamente positivos para o anticorpo contra o antígeno central da hepatite B (anti-HBc), mas nao reativos para o antígeno de superficie (HBsAg) assim como para o seu anticorpo (anti-HBs), podem ter seu teste falso-positivo, ser ainda portadores do VHB ou ter infecçao passada já resolvida. Doadores de sangue com esse padrao sorológico receberam vacina contra o vírus da hepatite B (VHB), com o intuito de estimular o surgimento de anti-HBs na circulaçäo. Dos 33 indivíduos incluidos no estudo, 13 (39por cento) positivaram o anti-HBs após uma dose de vacina. Dos 20 restantes, 15 (75por cento) aresentaram soroconversäo do anti-HBs após duas doses e um depois de tres doses. No total, 29 (88por cento) seroconverteram. Dos 33, 24 foram submetidos a pesquisa de DNA do VHB por tecnica de cadeia de polimerase. O exame foi negativo em todos. Os autores sugerem que estimular o surgimento de anti-HBs atraves de desafio de vacina contra o VHB pode ser uma maneira acessivel de tranquilizar os doadores de sangue com anti-HBc isolado que seroconverteram posteriormente, assegurando-lhes seu bom prognostico

Pesquisa de anticorpos contra o vírus da hepatite C em pool de 5 soros: sua utilizaçäo em inquéritos soroepidemiológicos / Detection of antibodies against hepatitis C virus in a 5 sera pool testing: its use in seroepidemiological survey

Para avaliar reduçäo de custo da pesquisa de anticorpos contra hepatite C, por ELISA, em pool de cinco soros, realizou-se o teste em grupos de baixo e alto risco. Dois terços dos conjuntos de alto risco tiveram que ser repetidos. A reduçäo do gasto de reagente foi de 80 por cento na populaçäo de baixo risco e de 13 por cento na amostra de alto risco. Estes dados sugerem que a pesquisa do anti-VHC em pool reduz o custo do procedimento em populaçöes de baixo risco

Infecçäo pelos vírus das hepatites B e C entre odontólogos de Cuiabá e Várzea Grande, Estado de Mato Grosso / Hepatitis B and C virus infection among dentists of Cuiabá and Várzea Grande, Mato Grosso state

A infecçäo pelos vírus das hepatites B(VHB) e C(VHC), entre odontólogos da regiäo metropolitana de Cuiabá, Mato Grosso, foi o objeto deste inquérito epidemiológico. A amostra contou com 106 voluntários, dentre os 480 dentistas que compareceram à campanha de imunizaçäo contra hepatite B em 1995, quando nä se identificaram portadores de hepatite B ou C. O anticorpo contra o antígeno de superfície do VHB(anti-HBs) foi positivo em 36 por cento, principalmente nos indivíduos que já haviam recebido doses de vacina contra a hepatite B anteriormente. O anticorpo contra o antígeno central da hepatite B(anti-HBc), testado nos indivíduos com anti-HBs, foi positivo em 50 por cento deles. O marcador de infecçäo prévia pelo vírus da hepatite B foi mais detectado nos profissionais nä vacinados ou naqueles com esquema incompleto de imunizaçäo.

Diagnóstico de paracoccidioidomicose disseminada grave em aspirado de medula óssea: relato de caso / Severe disseminated paracoccidioidomycosis diagnosis in bone marrow aspirate: a case report

Acute or chronic disseminated paracoccidioidomycosis can be associated with changes in blood and bone marrow cell counts, mainly in the severe forms of this disease. However, there are few reports about the microbiological confirmation of the mycosis in bone marrow tissue. The present report describes a case of an adult patient with severe chronic multifocal paracoccidioidomycosis, whose etiological diagnosis has been done by the microscopical exam and culture fo the bone marrow aspirate. The authors emphasize the importance of these exams as an alternative way for the diagnosis of suspected cases of severe paracoccidioidomycosis.