HEADINGS -Rats. Experimental surgery. Physiology.RESUMO -Racional -Milhões de ratos são empregados anualmente em pesquisas e no ensino. A exata relação entre a idade dos ratos, comparada com a idade dos humanos ainda é assunto de discussão e controvérsias. Objetivo -É revisar a literatura, analisando a idade dos ratos em comparação com a idade dos homens. Métodos -Foram revisadas as publicações existentes sobre o assunto contidas nas bases Medline/Pubmed, Scielo, Biblioteca Cochrane e Lilacs cruzando os descritores ratos, cirurgia experimental e fisiologia. Resultados -Ratos desenvolvem rapidamente durante a infância e se tornam sexualmente maduros com cerca de seis semanas de idade, mas atingem a maturidade social cinco a seis meses mais tarde. Na idade adulta, a cada mês do animal é aproximadamente equivalente a 2,5 anos humanos. Vários autores realizaram trabalhos experimentais em ratos e afirmaram existir Correspondence de 30 dias de vida do homem para cada dia de vida do rato. Conclusão -As diferenças na anatomia, fisiologia, desenvolvimento e fenômenos biológicos devem ser levados em consideração quando são analisados os resultados de qualquer pesquisa em ratos em que a idade é um fator crucial. Cuidado especial é necessário ser tomado quando os estudos efetuados pretendem produzir correlação com a vida humana. Para isso, atenção especial é necessária para verificar a fase em dias do animal e sua correlação com os anos em humanos. ABCDDV/836ABSTRACT -Background -Millions of mice are used annually in research and teaching. The exact relationship between age of the animals compared with the age of humans is still subject to discussion and controversy. Objective -Literature review analyzing the age of rats in comparison with men age. Methods -Were reviewed the existing publications on the subject contained in Medline / Pubmed, Scielo, The Cochrane Database of Systematic Reviews and Lilacs crossing the headings rats, experimental surgery and physiology. Results -Rats rapidly develop during childhood and become sexually mature at about six weeks old, but reach social maturity five to six months later. In adulthood, every month of the animal is approximately equivalent to 2.5 human years. Several authors performed experimental studies in rats and estimated 30 days of human life for every day life of the animal. Conclusion -The differences in anatomy, physiology, development and biological phenomena must be taken into consideration when analyzing the results of any research in rats when age is a crucial factor. Special care is necessary to be taken when the intention is to produce correlation with human life. For this, special attention is needed to verify the phase in days of the animal and its correlation with age in years of humans

The presence of HSV, mainly HSV-1, and Candida spp. was associated with mucositis severity in pediatric ALL. No association could be found between bacterial CFU and severity of mucositis.

The online version of this article contains a supplementary appendix. BackgroundMinimal residual disease is an important independent prognostic factor in childhood acute lymphoblastic leukemia. The classical detection methods such as multiparameter flow cytometry and real-time quantitative polymerase chain reaction analysis are expensive, time-consuming and complex, and require considerable technical expertise. Design and MethodsWe analyzed 229 consecutive children with acute lymphoblastic leukemia treated according to the GBTLI-99 protocol at three different Brazilian centers. Minimal residual disease was analyzed in bone marrow samples at diagnosis and on days 14 and 28 by conventional homo/heteroduplex polymerase chain reaction using a simplified approach with consensus primers for IG and TCR gene rearrangements. ResultsAt least one marker was detected by polymerase chain reaction in 96.4% of the patients. By combining the minimal residual disease results obtained on days 14 and 28, three different prognostic groups were identified: minimal residual disease negative on days 14 and 28, positive on day 14/negative on day 28, and positive on both. Five-year event-free survival rates were 85%, 75.6%, and 27.8%, respectively (p<0.0001). The same pattern of stratification held true for the group of intensively treated children. When analyzed in other subgroups of patients such as those at standard and high risk at diagnosis, those with positive B-derived CD10, patients positive for the TEL/AML1 transcript, and patients in morphological remission on a day 28 marrow, the event-free survival rate was found to be significantly lower in patients with positive minimal residual disease on day 28. Multivariate analysis demonstrated that the detection of minimal residual disease on day 28 is the most significant prognostic factor. ConclusionsThis simplified strategy for detection of minimal residual disease was feasible, reproducible, cheaper and simpler when compared with other methods, and allowed powerful discrimination between children with acute lymphoblastic leukemia with a good and poor outcome.

the presence of HSV, platelet count, and Candida spp. presence at D14 of ALL induction treatment is associated with increased severity of mucositis in children and adolescents. At D56 of ALL treatment, mucositis severity was associated with neutrophil count, HSV presence, and previous presence of HSV (at D14).

Ventral root avulsion (VRA) triggers a strong glial reaction which contributes to neuronal loss, as well as to synaptic detachment. To overcome the degenerative effects of VRA, treatments with neurotrophic factors and stem cells have been proposed. Thus, we investigated neuroprotection elicited by human embryonic stem cells (hESC), modified to overexpress a human fibroblast growth factor 2 (FGF-2), on motoneurons subjected to VRA. Lewis rats were submitted to VRA (L4-L6) and hESC/FGF-2 were applied to the injury site using a fibrin scaffold. The spinal cords were processed to evaluate neuronal survival, synaptic stability, and glial reactivity two weeks post lesion. Then, qRT-PCR was used to assess gene expression of β2-microglobulin (β2m), TNFα, IL1β, IL6 and IL10 in the spinal cord in vivo and FGF2 mRNA levels in hESC in vitro. The results indicate that hESC overexpressing FGF2 significantly rescued avulsed motoneurons, preserving synaptic covering and reducing astroglial reactivity. The cells were also shown to express BDNF and GDNF at the site of injury. Additionally, engraftment of hESC led to a significant reduction in mRNA levels of TNFα at the spinal cord ventral horn, indicating their immunomodulatory properties. Overall, the present data suggest that hESC overexpressing FGF2 are neuroprotective and can shift gene expression towards an anti-inflammatory environment.

Paulino LC, Araujo M, Guerra Jr G, Marini SHVL, De Mello MP. Mutation distribution and CYP21/C4 locus variability in Brazilian families with the classical form of the 21-hydroxylase deficiency. Acta Paediatr 1999; 88: 275-83. Stockholm. ISSN 0803-5253 Deficiency of adrenal steroid 21-hydroxylase is the most common form of congenital adrenal hyperplasia and it is considered to be responsible for 90% of the disease. This paper describes for the first time the CYP21B mutation profile in Brazilian patients. We genotyped 41 families with at least one individual affected with the classical form of the 21-hydroxylase deficiency, representing 74 unrelated alleles. In order to characterize different disease-causing alleles, genotyping was performed by Southern blot analysis with three restriction enzymes, allele-specific oligonucleotide hybridization, and allele-specific PCR. Different alleles were distinguished by TaqI C4B RFLP, gene duplications or deletions of either CYP21A C4B or CYP21B C4B, large gene conversions and eight mutations that might have been introduced into CYP21B from CYP21A by microconversion events. At least one mutation was detected in 24 different disease-causing alleles, which represents about 85% of the affected alleles in those families. The frequency of the 30 kb deletion of CYP21B was lower than that described for Caucasians. The mutation Sp2 showed the highest frequency (24.65%) and was present mainly in salt-wasting patients, although it was also detected in some patients with the simple virilizing form of the disease. Conversely, I172N showed a frequency of 18.91% and was found mostly in patients affected with the simple virilizing form of the disease. Five other mutations were determined at low frequency, but CL6 was not found in any of the tested alleles. & CAH alleles, congenital adrenal hyperplasia, CYP21B mutational analysis, steroid 21-hydroxylase

BackgroundCongenital adrenal hyperplasia due to 21-hydroxylase deficiency is caused by deletions, large gene conversions or mutations in CYP21A2 gene. The human gene is located at 6p21.3 within a locus containing the genes for putative serine/threonine Kinase RP, complement C4, steroid 21-hydroxylase CYP21 tenascin TNX, normally, in a duplicated cluster known as RCCX module. The CYP21 extra copy is a pseudogene (CYP21A1P). In Brazil, 30-kb deletion forming monomodular alleles that carry chimeric CYP21A1P/A2 genes corresponds to ~9% of disease-causing alleles. Such alleles are considered to result from unequal crossovers within the bimodular C4/CYP21 locus. Depending on the localization of recombination breakpoint, different alleles can be generated conferring the locus high degree of allelic variability. The purpose of the study was to investigate the variability of deleted alleles in patients with 21-hydroxylase deficiency.MethodsWe used different techniques to investigate the variability of 30-kb deletion alleles in patients with 21-hydroxylase deficiency. Alleles were first selected after Southern blotting. The composition of CYP21A1P/A2 chimeric genes was investigated by ASO-PCR and MLPA analyses followed by sequencing to refine the location of recombination breakpoints. Twenty patients carrying at least one allele with C4/CYP21 30-kb deletion were included in the study.ResultsAn allele carrying a CYP21A1P/A2 chimeric gene was found unusually associated to a C4B/C4A Taq I 6.4-kb fragment, generally associated to C4B and CYP21A1P deletions. A novel haplotype bearing both p.P34L and p.H62L, novel and rare mutations, respectively, was identified in exon 1, however p.P30L, the most frequent pseudogene-derived mutation in this exon, was absent. Four unrelated patients showed this haplotype. Absence of p.P34L in CYP21A1P of normal controls indicated that it is not derived from pseudogene. In addition, the combination of different approaches revealed nine haplotypes for deleted 21-hydroxylase deficiency alleles.ConclusionsThis study demonstrated high allelic variability for 30-kb deletion in patients with 21-hydroxylase deficiency indicating that a founder effect might be improbable for most monomodular alleles carrying CYP21A1P/A2 chimeric genes in Brazil.

Purpose: To investigate whether polydextrose stimulates iron absorption in rats submitted to partial gastrectomy and sham operated. Methods: The rats were submitted to partial gastrectomy (Billroth II) or laparotomy (sham-operated control), in groups of 20 and 20 each respectively. The animals were fed with a control diet (AIN-93M) without polydextrose or a diet containing polydextrose (50g/Kg of diet) for eight weeks. They were divided into four subgroups: sham-operated and Billroth II gastrectomy and with or without polydextrose. Two animals died during the experiment. All rats submitted to gastrectomy received B-12 vitamin (intramuscular) each two weeks. The hematocrit and hemoglobin concentration were measured at the start and on day 30 and 56 after the beginning of the experimental period. At the end of the study, the blood was collected for determination of serum iron concentration. Results: The diet with polydextrose reduced the excretion of iron. Apparent iron absorption was higher in the polydextrose fed groups than in the control group. The haematocrit and haemoglobin concentration were lower after Billroth II gastrectomy rats fed the control diet as compared to the polydextrose diet groups. Conclusion: Polydextrose increase iron absorption and prevents postgastrectomy anemia. Key words: Prebiotics. Gastrectomy. Iron. Anemia. Rats. RESUMOObjetivo: Investigar se a polidextrose estimula a absorção de ferro em ratos submetidos à gastrectomia parcial e sham operados. Métodos: Os ratos foram submetidos à gastrectomia parcial (Billroth II) e à laparotomia (controle sham-operados) em grupos de 20 e 20 cada, respectivamente. Os animais foram alimentados com uma dieta controle (AIN-93M), sem polidextrose ou uma dieta contendo polidextrose (50g/kg de dieta) durante oito semanas. Foram divididos em quatro grupos: sham-operados e com gastrectomia BII e com ou sem polidextrose. Dois animais morreram durante o experimento. Todos os ratos com gastrectomia receberam vitamina B-12 (intramuscular) a cada duas semanas. O hematócrito e a hemoglobina foram dosados no início e nos dias 30 e 56 após o início do período experimental. No final do estudo, o sangue foi coletado para determinação da concentração de ferro sérico. Resultados: A dieta com polidextrose reduziu a excreção de ferro e a absorção de ferro aparente foi maior nos grupos alimentados com polidextrose do que no grupo controle. As dosagens de hematócrito e hemoglobina foram menores em ratos com gastrectomia alimentados com a dieta controle em relação aos grupos de dieta com polidextrose. Conclusão: A polidextrose aumenta a absorção do ferro e previne a anemia pós-gastrectomia.