Recombinogenic, genotoxic, and cytotoxic effects of azathioprine using in vivo assays.

Azathioprine (Aza) is a purine antimetabolite immunosuppressant that is widely employed for immunosuppressive therapy in post-transplant recipients or patients with autoimmune diseases. Chronic use of immunosuppressants might produce several side effects, including a high rate of neoplasms in these patients. Considering that genotoxic effects are associated with an increased risk of developing cancer, the aim of this study was to examine the recombinogenic, genotoxic, and cytotoxic effects of Aza using Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster, as well as comet and micronucleus assays in mouse bone marrow cells. Further, the adverse effects of Aza were determined in mouse hepatic and renal tissues using histopathological analysis. Data demonstrated that Aza induced significant increased genotoxicity in D. melanogaster and mouse bone marrow cells at all concentrations tested. Homologous recombination was the predominant genotoxic event noted for the first time to be initiated by Aza in SMART. In histopathological analysis, Aza did not show any marked toxic activity in mouse hepatic and renal tissues. Therefore, the high rate of neoplasms reported in patients with long-term use of Aza may be attributed, at least partially, to the genotoxic action of this drug.

Wear, roughness and microhardness analyses of single increment restorative materials submitted to different challenges in vitro.

PURPOSE: To evaluate the microhardness, roughness, profilometry and cross-sectional hardness of single increment materials submitted to different challenges. METHODS: Thirty-six disks of each material, Filtek Supreme XTE (FT), Filtek One Bulk Fill (BK), Ketac Molar Easy Mix (KT) and Equia Forte + Coat (EQ) were immersed in saliva, pH cycling and Coke for 15 days. Half of each surface was used as its own control. Superficial microhardness, roughness, perfilometry analysis were performed. All samples were sectioned, embedded in acrylic resins, polished and cross-sectional hardness were made. Data were analyzed by ANOVA and Tukey's test (p < 0.05). RESULTS: The KT presented superficial microhardness superior than EQ. However, in depth, EQ showed superior values. FT, KT suffered the effects of challenges on microhardness values. The highest roughness and wear values were found for KT. RC do not suffer wear. All materials suffered the effects of Coke and pH challenges in depths 10 µm and 60 µm. CONCLUSION: The single increment restorative material that suffered less action on its surface was the bulk-fill resin. The coat present in the hybrid ionomer was able to resist to the immersion actions. In addition, Coke was the most aggressive challenge.

Inhibition of the P2X7 receptor improves renal function via renin-angiotensin system and nitric oxide on diabetic nephropathy in rats.

AIM: To evaluate the effects of P2X7 receptor blockade on renin-angiotensin system (RAS) in rats with diabetic nephropathy (DN). MAIN METHODS: Wistar rats were unilaterally nephrectomized and received streptozotocin for diabetes mellitus (DM) induction; control animals (CTL) received the drug vehicle. The animals were submitted to P2X7 receptor silencing, forming the group (DM + siRNA). The animals were placed in metabolic cages for data collection and evaluation of renal function; at the end of the protocol, the kidney was removed for analysis of P2X7, renin, angiotensin-converting enzyme (ACE), ACE2, angiotensin, thiobarbituric acid reactive substance levels (TBARS), nitric oxide (NO) and qualitative histological. KEY FINDINGS: The metabolic profile was attenuated in DM + siRNA vs. DM and there was a significant improvement in creatinine, urea and proteinuria levels in the same group. Renin expression was significantly decreased in DM + siRNA vs. DM. ACE and ACE2 were significantly reduced in DM + siRNA vs. DM. TBARS levels were decreased and NO showed an increase in DM + siRNA vs. DM, both significant. All histological alterations were improved in DM + siRNA vs. DM. SIGNIFICANCE: Data have shown that although silencing of the P2X7 receptor did not decrease fasting glucose, it promoted an improvement in the metabolic profile and a significant recovery of renal function, revealing a protective action by the inhibition of this receptor. This effect must have occurred due to the inhibition of RAS and the increase of NO, suggesting that the use of P2X7 receptors inhibitors could be used as adjuvant therapy against DN progression.

The erythrocyte alloimmunisation in patients with sickle cell anaemia: a systematic review.

Transfusion therapy is a common practice in the treatment of anaemia and can cause erythrocyte alloimmunisation. To systematise data related to erythrocyte alloimmunisation in patients with sickle cell disease (SCD), a bibliographic search was carried out in September 2017 to search for studies in four electronic databases. (i) Referring to the original work, (ii) being cohort or case-control, (iii) having been developed with individuals with SCD and (iv) having evaluated the erythrocyte alloimmunisation. Two reviewers identified the articles for inclusion in the study, extracted the predetermined data and carried out the evaluation of the methodological quality of the work. 21 studies were selected; the studies included data on 20 636 individuals (children and adults), were mostly published in the last 10 years, were developed in the United States and had high methodological quality. The occurrence of erythrocyte alloimmunisation ranged from 4·4 to 76%, and there was a higher rate of alloimmunisation against antigens of the Rh system. The risk factors for alloimmunisation were age; gender (female); red blood cell (RBC) units received; presence of ≥1 autoantibodies, TNF-α, interleukin (IL1B), human leukocyte antigens (HLA)-DRB1 gene polymorphisms; first blood transfusion (BT) after 5 years of age, transfusion episodic, multiple or during inflammatory events, acute chest syndrome (ACS) and vase-occlusive crisis (VOC); increased percentage of CD41 T memory cells; and positive direct antiglobulin test. Transfusion policies should be developed to protect the patient and his or her health based on the main factors associated with its incidence.

Surveillance of Arboviruses in Primates and Sloths in the Atlantic Forest, Bahia, Brazil.

From 2006 through 2014, we conducted seroepidemiological surveys on non-human primates and sloths to investigate the possible circulation of arboviruses in Bahia Atlantic Forest, Brazil. We collected a total of 196 samples from 103 Leontopithecus chrysomelas, 7 Sapajus xanthosternos, 22 Bradypus torquatus and 7 Bradypus variegatus. Serum samples were tested using neutralization test and hemagglutination inhibition test to detect total antibodies against 26 different arboviruses. The overall prevalence of arboviruses was 36.6% (51/139), with the genus Flavivirus having the highest prevalence (33.1%; 46/139), followed by Phlebovirus (5.0%; 7/139), Orthobunyavirus (4.3%; 6/139) and Alphavirus (0.7%; 1/139). Monotypic reactions suggest that the wild animals were exposed naturally to at least twelve arboviruses. Added results from the neutralization test, animals were exposed to thirteen arboviruses. Most of these viruses are maintained in transmission cycles independent of human hosts, although antibodies against dengue virus serotypes 1, 2 and 3 were found in this study. To our knowledge, this is the first study reporting exposure to arboviruses in L. chrysomelas, S. xanthosternos and B. torquatus. Our results also highlight that the Southern Bahia Atlantic Forest has a variety of vertebrate hosts and potential vectors, which may support the emergence or re-emergence of arboviruses, including those pathogenic to humans.

Latex sensitization in patients with myelomeningocele: contribution of microarray technique.

Summary: Background. Microarray technique employing molecular allergens is pointed out as a new method to evaluate allergic patients. Objective. To evaluate if microarray technique (ImmunoCAP-ISAC®; I-ISAC®) is similar to fluorescence enzyme immunoassay (FEIA; ImmunoCAP®) in the diagnosis of latex allergy (specific IgE to latex plus symptoms) and latex sensitization (only antibody) in pediatric (9-mo to 14-yrs) patients with myelomeningocele undergone to surgical repair. Methods. Patients underwent skin prick testing (SPT) to latex and food (prick to prick), and dosage of serum specific IgE to latex and recombinant latex allergens (rHev b 1, rHev b 3, rHev b 5, rHev b 6.01, rHev b 6.02, rHev b 8, rHev b 9, and rHev b 11) by ImmunoCAP® and I-ISAC®. Results. The comparison between the two methods showed high level of concordance considering positive and negative results. A statistically significant correlation for rHev b 3 and rHev b 6.01 for the allergic patients, and for rHev b5 and rHev b6.01 for those sensitized to latex, was observed. I-ISAC® is limited to 5 recombinant latex allergens (rHev b 1, 3, 5, 6.01 and 8). Despite the presence of antibodies against pollens, LTP and profilins (I-ISAC®) in some patients, none of them reported symptoms related with intake of fruits and/or vegetables. Conclusion. Both methods are effective in assisting the diagnosis of latex allergy, but differ in the assessment of sensitized pediatric patients with myelomeningocele. The assessment of latex sensitized patients is more complete using the 8 recombinant latex fractions available for ImmunoCAP®, instead of I-ISAC®.

Description of a new species Fuhrmannetta jurubatensis n. sp. (Cestoda, Davaineidae) from Cerradomys goytaca Tavares, Pessôa & Gonçalves, 2011 (Rodentia, Cricetidae).

A new species of cestode of the genus Fuhrmannetta found in the small intestine of Cerradomys goytaca is described herein, named Fuhrmannetta jurubatensis n. sp. Rodents were collected from the sand-plains areas of the northern coast of the State of Rio de Janeiro, Brazil. Morphological analyses were conducted by light and scanning electron microscopy. From the morphological analysis and a comparison with the known species of the genus, F. jurubatensis n. sp. can be identified by a combination of morphological and morphometrical characteristics, including strobila length, number and length of rostellar hooks, position of the genital pore and the number of eggs per uterine capsule.

Effects of whole body vibration on bone mineral density in postmenopausal women: a systematic review and meta-analysis.

UNLABELLED: This systematic review and meta-analysis of randomized controlled trials (RCTs) identified significant effects of whole body vibration (WBV) on bone mineral density (BMD) of the lumbar spine (in the sensitivity analysis and seven subgroup analyses), femoral neck (in one subgroup analysis), and trochanter (four subgroup analyses) in postmenopausal women, but not other measurements of BMD. INTRODUCTION: Interventions using WBV training have been conducted in postmenopausal women, aimed at increasing BMD; however, the results are contradictory. Our objective is to conduct a systematic review and meta-analysis of RCTs examining WBV effect on BMD. METHODS: RCTs were considered eligible, with follow-up ≥6 months, which verified the effects of WBV on the BMD of postmenopausal women. The calculations of the meta-analysis were performed through the weighted mean difference between the WBV and control groups, or the WBV and combined training, through the absolute change between pre- and post-intervention in the areal bone mineral density (aBMD) or trabecular volumetric bone mineral density (vBMDt). RESULTS: Fifteen RCTs were included in the meta-analysis. No differences were observed in the primary analysis. WBV was found to improve aBMD compared with the control group, after exclusion of studies with low quality methodological (lumbar spine), when excluding the studies which combined WBV with medication or combined training (lumbar spine), with the use of low frequency and high magnitude (lumbar spine and trochanter), high frequency and low magnitude (lumbar spine), high cumulative dose and low magnitude (lumbar spine), low cumulative dose and high magnitude (lumbar spine and trochanter), with semi-flexed knee (lumbar spine, femoral neck, and trochanter), and side-alternating type of vibration (lumbar spine and trochanter). CONCLUSIONS: Despite WBV presenting potential to act as a coadjuvant in the prevention or treatment of osteoporosis, especially for aBMD of the lumbar spine, the ideal intervention is not yet clear. Our subgroup analyses helped to demonstrate the various factors which appear to influence the effects of WBV on BMD, contributing to clinical practice and the definition of protocols for future interventions.

Haematological recovery in poor and good haematopoietic stem cell mobilisers.

OBJECTIVES: Evaluate whether poor mobilisers had delayed haematopoietic (neutrophil and platelet) recovery despite receiving similar cell dose as good mobilisers. BACKGROUND: Autologous haematopoietic progenitor cell (HPC) transplantation is indicated to treat some haematological malignancies. This procedure requires HPC mobilisation from bone marrow to peripheral blood. Cell dose is important for a fast haematological recovery. Despite being poor mobilisers, some patients can collect enough cell numbers for transplantation. RESULTS: Fifteen poor mobiliser patients (peak of CD34+ cells ≤10 µL(-1) in peripheral blood) were transplanted at our institution. Haematological recovery (neutrophil ≥ 500 µL(-1) ) in this group was compared to that observed in the group of 16 patients of good mobilisers (peak of CD34+ cells ≥20 µL(-1) in peripheral blood) who received similar cell dose (2·637 ± 0·1744 × 10(6) kg(-1) vs 2·727 ± 0·1746 × 10(6) kg(-1) ; P = 0·7177). The poor mobiliser group had neutrophil and platelet recovery later than the good mobiliser group (on day 12, range 9-14 vs day 10, range 9-22, P = 0·0381 for neutrophil, and on day 22·89 ± 11·16 and 14·08 ± 4·821, P = 0·0193 for platelet). Mortality rates and transfusion requirements were not different between the groups. CONCLUSION: Poor mobilisers have delayed neutrophil and platelet recovery after autologous HPC transplantation despite having received the same cell dose as good mobilisers.

An effective approach for modifying carbonaceous materials with niobium single sites to improve their catalytic properties.

In this paper we show a very simple route for the incorporation of catalytically active niobium species on the surface of carbon materials, such as graphene oxide, carbon nanotubes and activated carbon. Some existing methods of incorporating a transition metal on a support have involved co-precipitation or wet impregnation, to obtain the corresponding oxides. These methods, however, cause reduction in the specific area of the support and can also form large metal oxide particles with loss of metal exposure. Therefore, here we present a novel way to add catalytically active species on the surfaces of different types of carbon through the formation of interaction complexes between the metal precursor and the functional groups of the carbon matrix. Because of the excellent catalytic properties exhibited by the niobium species we choose the NH4[NbO(C2O4)2(H2O)2]·2H2O salt as the model precursor. The characterization by XPS reveals the presence of the niobium species indicated by the displacement of the peaks between 206-212 eV related to the oxalate species according to the spectrum from pure niobium oxalate. Images obtained by TEM and SEM show the typical morphologies of carbonaceous materials without the niobium oxide formation signal, which indicates the presence of niobium complexes as isolated sites on the carbon surfaces. This new class of materials exhibited excellent properties as catalysts for pollutant oxidation. The presence of Nb promotes the catalytic activation of H2O2 generating hydroxyl radicals in situ, which allows their use in the organic compound oxidation processes. Tests for DBT oxidation indicate that Nb significantly improves the removal of such pollutants in biphasic reactions with removal around 90% under the tested conditions. Theoretical calculations showed that the most favorable adsorption model is an ionic complex presenting a ΔG = -108.7 kcal mol(-1) for the whole adsorption process.

Karyotype structure of Hypostomus cf. plecostomus (Linnaeus, 1758) from Tapajós River basin, Southern Amazon: occurrence of sex chromosomes (ZZ/ZW) and their evolutionary implications.

Hypostomus is a group of fish with numerical and struc-tural karyotypic variability. Among them, only six species, three of which belong to the Amazon basin, show a sex chromosome. In this study, we present the karyotype structure of Hypostomus cf. plecos-tomus from the Teles Pires river basin in the municipality of Alta Flo-resta, MT. The species has 2n = 68 and the karyotype formula 14m+ 24sm+ 14st+ 16a [fundamental number (FN) = 120] in males and 15m+ 24sm+14st+15a (FN = 121) in females and sex chromosomes ZZ/ZW. Argyrophilic nucleolar organizer regions (AgNORs) were identified in two pairs of chromosomes at different positions: short arm of the pair 21and long arm of the pair 27, matching the signals displayed by 18S FISH and indicating multiple NORs. Analysis of band C detected few blocks of constitutive heterochromatin in the pericentromeric regions of most chromosomes and the telomeric regions of some pairs, includ-ing the nucleolar pair 21. However, large blocks on the long arm of the nucleolar pair 27 still stood out. GC-rich heterochromatin (CMA3) was visualized only coincidently with nucleolar sites. Mapping of 5S rDNA sites with FISH revealed markings in eight chromosomes, demonstrat-ing synteny between the 18S and 5S sites. The data obtained for H. cf. plecostomus are important for taxonomic studies of this Amazon com-plex "H. plecostomus group". The occurrence of sex chromosomes in Amazon species of Hypostomus suggests an evolutionary event that is independent of other species in the group.

Cytogenetic description of Ancistrus abilhoai (Siluriformes: Loricariidae) from Iguaçu River basin, southern Brazil.

The Iguaçu River basin is a tributary to the upper Paraná River in southern Brazil, and is considered an important aquatic ecoregion that, although having few species of fish, 51-71% of these are apparently endemic. Ancistrus abilhoai is one of three recently described species for this basin and is currently considered endemic to the basin. In this study, we present the chromosomal structure of two populations of Ancistrus abilhoai one collected in the Iguaçu River, in Paraná State, and another collected in the Timbó River, a tributary of the Iguaçu River, in the State of Santa Catarina. Karyotype analyzes were performed in 11 specimens from the Iguaçu River (four females and seven males) and 12 specimens (all males) from Timbó River, revealing 2n = 48 chromosomes with a karyotype formula of 22m + 14sm + 6st + 6a in both populations. Analysis of active nucleolar organizer regions (Ag-NORs) and fluorescent in situ hybridization (FISH) with 18S rDNA probes revealed the submetacentric pair 13 bearing marks at terminal positions on the short arms. Considered as plesiomorphic chromosomal markers in Loricariidae, asynteny 18S and 5S rDNA, and small amounts of heterochromatin were observed. In this study, the first chromosomal data of A. abilhoai are presented with comments on karyotypic characteristics of the genus.

Electromyographic analysis of rectus femoris activity during seated to standing position and walking in water and on dry land in healthy children and children with cerebral palsy.

PURPOSE: To analyze rectus femoris activity during seated to standing position and walking in water and on dry land comparing a group of children with the spastic diparesis type of cerebral palsy (CP) and a group of children without neurological disorders. METHODS: This study included a group of nine children with CP and a control group of 11 children. The study compared the electromyographic activity of the rectus femoris during seated to standing position and walking, in water and on land. RESULTS: A greater activation of the rectus femoris was observed in the group of children with CP compared with the control group when moving from a seated position to a standing position in water (p=0.0039) and while walking on land (p=0.0014) or in the pool (p=0.007). CONCLUSION: This study demonstrated the activation of the rectus femoris while walking or standing up from a seated position in water was greater in the group of children with CP. Further studies should be performed to better understand the extent of muscular activation during body immersion in individuals with neurological disorders.

Efeito de diferentes níveis de sombreamento no crescimento inicial de Unha de gato (Uncaria tomentosa Willd. ) / Effect of different levels of shading on the growth of cat's claw (Uncaria tomentosa Willd. ). Cat's claw (Uncaria tomentosa Willd. )

A unha de gato (Uncaria tomentosa Willd.) é uma das muitas espécies de plantas com propriedades medicinais utilizadas pelas comunidades nativas da Amazônia para o tratamento de diversas doenças. Suas inúmeras propriedades medicinais têm provocado nos últimos anos o aumento da demanda por essa planta, a qual vem sendo explorada de forma indiscriminada e predatória. O conhecimento agronômico disponível atualmente sobre essa espécie é escasso; dessa forma, o objetivo do presente trabalho foi avaliar o efeito de diferentes níveis de sombreamento no crescimento inicial da Unha de gato. O experimento foi realizado no viveiro da área experimental da Embrapa Acre, no município de Rio Branco, AC, no período de maio de 2009 a junho de 2010. Foram avaliados quatro tratamentos, constituídos por diferentes níveis de sombreamento (30%, 50% e 70%) e pleno Sol, obtidos com tela sombrite preta, com as referidas capacidades de retenção da radiação solar. O delineamento experimental utilizado foi o de blocos casualizados, com oito repetições, contendo duas plantas por parcela. As variáveis analisadas foram: altura da parte aérea, diâmetro do colo, biomassa do sistema radicular, biomassa aérea, biomassa total e partição de biomassa. O crescimento da Unha de gato foi modificado pela intensidade de sombreamento. A altura das plantas e a massa seca das raízes aumentaram linearmente com a intensidade de sombreamento. Sombreamentos entre 55 a 60% proporcionaram melhores crescimentos para as variáveis: diâmetro do coleto, massa seca da parte aérea e massa seca total. Não houve variação na distribuição de massa seca entre a parte aérea e o sistema radicular das plantas em função do sombreamento. Verificou-se que o sombreamento na faixa de 55 a 60% é o mais indicado para o seu crescimento inicial.

Is one among many plant species with medicinal properties, used by the native communities of the Amazon to treat several diseases. Its numerous medicinal properties have caused in recent years an increase in demand and the plant has been exploited in an indiscriminate and predatory way. The agronomic knowledge available on this species is scarce, so the purpose of this study was to evaluate the effect of different levels of shading on early growth of Uncaria tomentosa. The experiment was established in the nursery of Embrapa Acre, in the city of Rio Branco, state of Acre, Brazil, from May 2009 to June 2010. We tested four levels of shading (30%, 50% and 70%) and full sunlight, obtained with black shade screens. The experimental design was a randomized block, with eight replications and two plants per plot. The variables analyzed were: height of shoots, stem diameter, root dry matter, aerial dry matter, total dry matter and dry matter partitioning. The growth of Uncaria tomentosa was modified by the intensity of shading. Plant height and dry weight of the roots increased linearly with the intensity of shading. Shading around 55 to 60% provided better growth for the stem diameter, shoot dry matter and total dry matter. There was no change in the distribution of the dry matter between the shoot and root systems of the plants. For the species Uncaria tomentosa, we found that shading in the range of 55 to 60% is the most indicated for its early growth.

In silico prediction of conserved vaccine targets in Streptococcus agalactiae strains isolated from fish, cattle, and human samples.

Streptococcus agalactiae (Lancefield group B; group B streptococci) is a major pathogen that causes meningoencephalitis in fish, mastitis in cows, and neonatal sepsis and meningitis in humans. The available prophylactic measures for conserving human and animal health are not totally effective and have limitations. Effective vaccines against the different serotypes or genotypes of pathogenic strains from the various hosts would be useful. We used an in silico strategy to identify conserved vaccine candidates in 15 genomes of group B streptococci strains isolated from human, bovine, and fish samples. The degree of conservation, subcellular localization, and immunogenic potential of S. agalactiae proteins were investigated. We identified 36 antigenic proteins that were conserved in all 15 genomes. Among these proteins, 5 and 23 were shared only by human or fish strains, respectively. These potential vaccine targets may help develop effective vaccines that will help prevent S. agalactiae infection.

Radiation dose in cardiac CT angiography: protocols and image quality.

This paper aims to evaluate the radiation dose exposure of patients submitted to cardiac computed tomography angiography. The effective dose was obtained from the product of dose-length product values and the conversion factor established in the European Working Group for Guidelines on Quality Criteria in CT. The image noise and contrast- and signal-to-noise ratios were obtained for all images. Sixty-four- and 256-slice CT angiographies were used in 211 (68.5 %) and 97 (31.5 %) patients, respectively. The calculated mean effective dose with prospective CT angiography was 6.0±1.0 mSv and the retrospective mode was 8.4±1.2 mSv. The mean image noise values were 38.5±9.5 and 21.4 ± 5.3 for prospective and retrospective modes, respectively. It was observed that the image noise increased by 44.4 % using a prospective mode. Prospective CT angiography reduces radiation dose by ∼29 % compared with the retrospective mode, while maintaining diagnostic image quality and the ability to assess obstructions in patients.

Individual cow's milk allergens as prognostic markers for tolerance development?

BACKGROUND: Cow's milk allergy (CMA) is one of the most common causes of food allergy in the first years of life. Fortunately, the majority of children with CMA develop clinical tolerance with time. However, no good individual markers exist to predict whether this will occur. Therefore, a prognosis to identify children with persistent CMA at diagnosis would be helpful. OBJECTIVE: In this study, we sought to assess whether measurement of IgE to individual allergens of cow's milk (CM) would separate patients with persistent CMA from those who became clinically tolerant to CM over time. METHODS: A total of 52 patients ranging from 3 months to 114 months of age with proven CMA by DBPCFC were followed over time. From these 52 patients, 32 (61.5%) patients became tolerant in the analysed time period. All patients were rechallenged at least once, some were rechallenged two or three times. Serum was analysed prior to each challenge for specific IgE, IgG and IgG4 binding to crude CM protein as well as to individual allergens of CM. RESULTS: The individual likelihood of outgrowing CMA significantly correlates with a low level of CM-specific IgE as well as a low level of specific IgE to α-lactalbumin, ß-lactoglobulin (Bos d5.0102), κ-casein and α(s1) -casein. No significant correlation was found for IgE levels to total casein, lactoferrin, ß-casein and ß-lactoglobulin (Bos d5.0101) as well as IgG and IgG4 levels to α-lactalbumin, ß-lactoglobulin and total casein. CONCLUSIONS: CM-specific IgE is a good prognostic marker for persistence of CMA. In addition, component-resolved diagnostic showed similar results. However, in our view, the rising laboratory costs do not justify a measurement on a daily basis. Additional determination of specific IgG or IgG4 levels was not useful in predicting tolerance development in our study population.

Pain syndrome induced by calcineurin inhibitor and resolved by conversion to sirolimus in a child after kidney transplantation: a case report.

Pain induced by calcineurin inhibitors is a rare complication of unknown pathogenesis. We have reported herein a 7-year-old child who presented with abdominal pain, vomiting, and weight loss showing no significant findings after an extensive laboratory and imaging workup. After conversion from tacrolimus to sirolimus, there was complete resolution of the gastrointestinal symptoms and pain; the patient displays excellent renal function. Calcineurin inhibitor-induced pain syndrome is diagnosis of exclusion but must be considered because the withdrawal of this immunosuppressive agent is associated with improvement in symptoms and quality of life.