Risk factors for oral mucositis in patients with solid tumors under treatment with cetuximab: a retrospective cross-sectional study.

BACKGROUND: This study retrospectively analyzed the risk factors for oral mucositis (OM) during cetuximab treatment. MATERIAL AND METHODS: We screened patients using cetuximab and retrospectively evaluated the presence of OM based on medical records. We collected information from 2 years of evaluations. Patient medical records were reviewed to obtain data on chemotherapy cycle and dose, sex, age, primary tumor, TNM stage, and head and neck radiotherapy (HNR) history. The X2 test and multinomial logistic regression were used for statistical analysis (SPSS 20.0, p < 0.05). RESULTS: Among 1831 patients, OM was showed in 750 in any grade (41%), during cetuximab treatment. Most patients were female (n=944, 51.6%), <70years-old (n=1149, 62.8%), had larynx cancer (n=789, 43.1%) in T4 (n=579, 47.7%), N0 (n=509, 52.6%) stages. Primary tumor surgery was performed in 1476 (80.6%) patients, radiotherapy in 606 (33.1%) patients and cetuximab protocols most used involved up to four cycles (n=1072, 58.5%) of <400mg (n=996, 54.4%) cetuximab doses. Female (OR [odds ratio] = 2.17, CI95% = 1.26-3.75), >70 years-old patients (OR = 16.02, CI95% = 11.99-21.41), with HHNR (OR = 1.84, 1.41-2.40), treated with >4 cycles (OR = 1.52, CI95% = 1.16-2.01) and high doses of cetuximab (OR = 3.80, CI95% = 2.52-5.71) are the greatest risk factors for OM. CONCLUSIONS: Since the clinical benefit of cetuximab in the treatment of older patients is limited and there is a high OM, especially in women with head and neck treated with radiotherapy, high doses and a high number of cetuximab cycles must be administered with caution.

Comparison of a daily and alternate-day photobiomodulation protocol in the prevention of oral mucositis in patients undergoing radiochemotherapy for oral cancer: a triple-blind, controlled clinical trial.

BACKGROUND: Preventive Photobiomodulation Therapy (PBMT) significantly reduces oral mucositis (OM) severity in patients undergoing Radiochemotherapy (RCT) for the treatment of oral cancer, but daily applications generate cost, overload the dental team, and reduce the number of patients assisted.To evaluate the effectiveness of two PBMT protocols in preventing OM in patients undergoing RCT for oral cancer. MATERIAL AND METHODS: 16 patients diagnosed with oral cancer undergoing RCT were included, equally divided into two groups: a group treated daily with PBMT, and another group also submitted to daily treatment, however, performing the application of PBMT every three days, interspersed with a simulation of PBMT (placebo). A red laser was used (~660 nm), 0.1W power, 1J of energy applied per point, 9 points per area (labial mucosa, buccal mucosa, lateral borders of the tongue, body of the tongue, and floor of the mouth) from the beginning of RCT until the end of the oncological treatment. Daily assessments were performed regarding OM scores, the World Health Organization (WHO) pain scale, and the visual analog scale (VAS). Weight, salivary flow (SGAPP), OHIP-14, and DMFT were evaluated on the initial and final days of RT. OM incidence and clinical data were compared by Pearson's chi-square test or Fisher's exact test. Pain and other scale scores were compared using the Mann-Whitney and Friedman/Dunn tests (SPSS v20.0 p<0.05). RESULTS: In the group with PBMT on alternate days, there was an increase in the frequency of grade 2 and grade 3 oral mucositis and an increased risk of grade 2 oral mucositis, in addition to higher mean pain scores and greater reduction in salivary flow. CONCLUSIONS: The daily PBMT protocol proved more effective in controlling the frequency and severity of OM, pain, and salivary flow.

Dysgeusia increases the risk for death and other side effects during antineoplastic systemic treatment for solid tumors: a cross-sectional study.

BACKGROUND: Chemotherapy (CT) is a systemic treatment using a combination of antineoplastic drugs, orally or intravenously, that inhibit tumor growth and fast-growing normal cells. Due to its nonspecificity, chemotherapy can cause a series of adverse effects, such as altered taste (dysgeusia), associated with malnutrition and, consequently, other adverse effects in the gastrointestinal tract and increased mortality risk. This study aimed to evaluate the influence of dysgeusia on the incidence of other adverse effects and overall survival during antineoplastic chemotherapy. MATERIAL AND METHODS: An observational, retrospective, cross-sectional study was conducted using data from the Electronic Health Record system of the Cancer Institute of Ceará over two years. Before the CT session, the multi-professional team evaluated the patient for the presence and severity of adverse effects (AE), using scores from the CTCAE v5.0 scale. Dysgeusia scores were collected and associated with clinical pathological data, with other adverse effects (nausea, vomiting, diarrhea, oral mucositis, anorexia, constipation), and with overall survival. Chi-square and Mantel-Cox log-rank tests were used. RESULTS: Of 5744 patients evaluated, dysgeusia presented a frequency of 50.6%, being directly associated with female gender (p=0.001), overweight (p=0.022), high tumor stages (p=0.009), a combination of adjuvant and neoadjuvant (p=0.010) and four-year survival (p=0.030). Dysgeusia frequency was directly associated with diarrhea (p<0.001), anorexia (p<0.001), oral mucositis (p<0.001), nausea (p<0.001), constipation (p<0.001) and vomiting (p<0.001), and inversely associated with fatigue (p=0.035). CONCLUSIONS: Dysgeusia during CT increases the risk of other adverse effects and negatively impacts prognosis.

Risk factors for oral mucositis during chemotherapy treatment for solid tumors: a retrospective STROBE-guided study.

BACKGROUND: This study retrospectively analyzed the risk factors for transchemotherapy oral mucositis (OM). MATERIAL AND METHODS: Before each chemotherapy cycle, patients were routinely evaluated for the presence/severity of OM based on the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 scale for adverse effects and graded as follows: However, specific conditions such as mucositis are graded on a five-point scale: 0, absence of mucositis, grade 1 (Asymptomatic or mild), 2 (Presence of pain and moderate ulceration, without interference with food intake), 3 (severe pain with interference with food intake) or 4 (Life-threatening with the need for urgent intervention). Information from 2 years of evaluations was collected and patient medical records were reviewed to obtain data on chemotherapy cycle, sex, age, body mass index, body surface area, primary tumor, chemotherapy protocol, and history of head and neck radiotherapy. The X² test and multinomial logistic regression were used for statistical analysis (SPSS 20.0, p<0.05). RESULTS: Among 19,000 total evaluations of 3,529 patients during 5.32±4.7 chemotherapy cycles (CT) the prevalence of OM was 6.3% (n=1,195). Chemotherapy duration (p<0.001), female sex (p=0.001), adjuvant intention (p=0.008) and the use of carboplatin (p=0.001), cisplatin (p=0.029), docetaxel (p<0.001) and bevacizumab (p=0.026) independently increased the risk of mucositis. In head and neck tumors, 2018 year (p=0.017), chemotherapy duration (p=0.018), BMI>30 (p=0.008), radiotherapy (p=0.037) and use of carboplatin (p=0.046) and cyclophosphamide (p=0.010) increased this prevalence. CONCLUSIONS: Cycles of chemotherapy, sex, cytotoxicity drugs, bevacizumab and head and neck radiotherapy increase the risk of OM in solid tumors.

Effects of heat in the properties of NaOCl alone and mixed with etidronate and alkaline tetrasodium EDTA.

AIM: To assess the free available chlorine concentration (FAC), organic tissue dissolution and smear layer removal capacity of sodium hypochlorite (NaOCl) alone and when mixtured with etidronate (HEDP) and tetrasodium EDTA (Na4 EDTA), and heated to different temperatures. METHODOLOGY: Mixtures at 1 : 1 ratio of 5% NaOCl with distilled water (considered NaOCl alone), 18% HEDP or 10% Na4 EDTA were heated to 25 °C, 37 °C, 48 °C and 60 °C. The FAC in the mixtures was assessed at 5, 10, 20, 30, 60 and 120 min. Samples of bovine muscle tissue (n = 10) were prepared with similar size and weighed before and after 5, 10 and 15 min of immersion in the mixtures heated to the different temperatures to verify organic matter dissolution. The intergroup results were compared statistically using one-way analysis of variance (anova) and intragroup by two-way analysis of variance (anova), both followed by Tukey's multiple-comparison test (α < 0.01). Bovine dentine blocks (n = 10) were analysed by scanning electron microscopy before and after immersion in the mixtures, and the time taken to remove the smear layer from the surfaces of the samples was determined. The Friedman test was used to compare the scores of the same group (α < 0.01), and the Kruskal-Wallis test with Dunn's post hoc was used to compare the different groups (α < 0.01). Saline solution was used as a control in the experiments of tissue dissolution and smear layer removal, RESULTS: Heating NaOCl alone did not affect its FAC. The higher the temperature of the mixtures with the chelators, the lower the FAC. Organic tissue dissolution was improved by increases in temperature of NaOCl alone and its mixture with HEDP (P < 0.01); however, the mixture with Na4 EDTA had no improvement (P > 0.01). Smear layer removal by NaOCl alone was enhanced by heating resulting in lower scores in some samples and became more rapid in the mixtures with the chelators. The saline solution did not promote tissue dissolution nor smear layer removal (P > 0.01). CONCLUSION: In this laboratory study, heating NaOCl alone or when mixed with HEDP improved its capacity to dissolve organic matter and remove the smear layer. However, the mixture with HEDP required frequent refreshment to retain these effects when heated. Due to the acceleration in the reaction between the irrigants, very rapid reductions in the free available chlorine in the mixtures with Na4 EDTA heated to the different temperatures occurred.

Clinical-pathological and sociodemographic factors associated with the distant metastasis and overall survival of oral cavity and oropharynx squamous cell carcinoma.

BACKGROUND: The objective of this study was to evaluate the influence of clinical-pathological and sociodemographic factors on the prevalence of distant metastasis (DM) and overall survival in patients with oral cavity and oropharynx squamous cell carcinoma (OOSCC). MATERIAL AND METHODS: Cross-sectional study based on the records of 404 OOSCC patients evaluated for DM, covering the period 2000-2014. We analysed the influence of age, sex, level of schooling, primary tumor subsite, treatment, marital status, family history of cancer, history of smoking and alcohol consumption, type of health care coverage (private vs. public) and overall survival. Findings were submitted to Fisher's exact test, Pearson's chi-squared test, Mantel-Cox log-rank testing and multinomial and Cox regression analysis (SPSS v. 20.0; p<0.05). RESULTS: The prevalence of DM was 5.4% (22/404). The respiratory tract was the most affected DM site (n=9; 40.9%). Male sex (p=0.049), oropharyngeal primary tumor (p=0.008), stage T3-4 (p=0.022), lymph node metastasis (N+) (p<0.001) and palliative treatment (p=0.005) were directly associated with DM. Patients with oral primary tumours (p=0.343) and primary oropharyngeal tumours (p=0.242) did not differ significantly with regard to the prevalence of DM. N+ was an independent risk factor for DM (p=0.017). Five variables independently reduced overall survival: male sex (p=0.035), age >65 years (p=0.046), indigenous/brown racial type (p=0.045), palliative treatment (p=0.035) and DM (p=0.048). CONCLUSIONS: Lymph node metastasis independently increased the prevalence of DM and, along with male sex, older age, brown racial type and palliative treatment, was independently associated with poor prognosis in patients with OOSCC.

Effect of larger apical size on the quality of preparation in curved canals using reciprocating instruments with different heat thermal treatments.

AIM: To evaluate the influence of larger apical canal enlargement in curved canals using reciprocating systems subjected to various heat treatments. METHODOLOGY: Ninety mandibular premolars with root curvatures ranging from 20° to 30° were selected and scanned by microcomputed tomography (micro-CT) before and after root canal preparation with reciprocating systems (n = 30): Reciproc Blue (RB size 25, .08 taper and size 40, .06 taper; VDW, Munich, Germany), WaveOne Gold (WOG size 25, .07 taper and size 35, .06 taper; Dentsply Sirona, Ballaigues, Switzerland) and ProDesign R (PDR size 25, .06 taper and size 35, .05 taper; Easy Dental Equipment, Belo Horizonte, Brazil). Canal transportation, untouched areas, and apical and total root canal volumes were measured. Statistical analysis was performed with the nonparametric Kruskal-Wallis and Dunn's tests and a significance level set at 5%. RESULTS: The between-group comparison revealed no significant difference in untouched areas, canal transportation, and apical root canal volume among the groups (P > 0.05). However, WOG size 35, .06 taper was associated with a significant increase in the percentage of total canal volume in comparison to the PDR size 35, .05 taper (P < 0.05). The within-group comparison revealed a significant decrease in untouched areas, increase in apical and total root canal volume for all groups when using a larger instrument (P < 0.05). There was no significant difference in transportation among the groups and when a larger apical preparation was created (P > 0.05). CONCLUSIONS: Larger apical enlargement of curved canals was associated with a decrease in untouched areas, an increase in root canal volume and maintenance of canal trajectory. In addition, all systems were safe and provided similar root canal shapes.

Sequence analysis of the S1PR1 gene in river buffalo.

Recent developments in methodologies for genomic analyses have enabled a significant advance in understanding of the river buffalo genome. The S1PR1 gene has been mapped to buffalo chromosome 6 and bovine chromosome 3; this gene is of interest as it is a candidate for marbling in meat, an important economic trait. Here, we performed next generation sequencing in a buffalo BAC DNA clone and obtained a 54.5-kb sequence encompassing the entire buffalo S1PR1 gene as well as the 27 kb upstream region and the 22 kb downstream region. The gene had a total length of 4716 bp, including three exons and two introns; exons 1 and 2 were classified as non-protein-coding. In comparison with homologues from other species, the structural organization of buffalo S1PR1 was closest to that of the goat and in both species exon 2 of the gene was non-protein-coding. One hundred and nine repetitive elements were found within the buffalo gene and its boundary regions, with 50 SINE repeats being the most abundant. Alignment of S1PR1 sequences from the Murrah and Mediterranean breeds revealed two nucleotide substitutions (g.1176C>G and g.2740T>C), which represent potential SNPs that could be used in further studies of buffalo genetic structure.

Molecular characterization of interferon regulatory factor 1 in Bubalus bubalis.

Interferon regulatory factor 1 (IRF1) is functionally diverse in the regulation of immune response and is considered to be an important candidate gene for studying disease susceptibility in mammals. In this paper, we characterized the whole sequence of the IRF1 gene in river buffalo (Bubalus bubalis) and compared genomic and the amino acid sequences between different species. The buffalo IRF1 gene was 7099 bp long and organized into 10 exons and nine introns. Its molecular structure showed exactly the same number of exons (10) and introns (nine) in bovids, mice, horses, humans, and chickens. However, rats did not have exon 5, but had the largest exon 4, which suggests that exon 5 was incorporated into exon 4. The coding and the amino acid sequences of the gene showed that identity varied from 73 to 99% at the coding sequence level and from 61 to 100% at the amino acid level when compared with other mammals and chickens. Comparative analysis of the gene sequence between two different buffalo breeds, Murrah and Mediterranean, revealed six potential SNPs that are primarily located in the 5' and 3'UTRs.

Sequence characterization and comparative analysis of the gastrotropin gene in buffalo (Bubalus bubalis).

In this study, we compared the complete sequence of the FABP6 gene from an animal representing the Murrah breed of the river buffalo (Bubalus bubalis) with the gene sequence from different mammals. The buffalo FABP6 gene is 6105 bp in length and is organized into four exons (67, 176, 90, and 54 bp), three introns (1167, 1737, and 2649 bp), a 5ꞌUTR (93 bp), and a 3ꞌUTR (72 bp). A total of 22 repetitive elements were identified at the intronic level, and four of these (L1MC, L1M5, MIRb, and Charlie4z) were identified as being exclusive to buffalo. Comparative analysis between the FABP6 gene coding sequence and the amino acid sequence with its homologues from other mammalian species showed a percentage of identity varying from 79 to 98% at the DNA coding level and 70 to 96% at the amino acid level. In addition, the alignment of the gene sequence between the Murrah and the Mediterranean breeds revealed 20 potential single nucleotide polymorphisms, which could be candidates for validation in commercial buffalo populations.

Comparative analysis of the river buffalo somatostatin gene.

The somatostatin protein plays a crucial role in the regulation of multiple biological functions, such as growth, fat deposition, and nutrient absorption in vertebrates. Polymorphisms in the somatostatin gene have been associated with growth traits in livestock species, including cattle and goat. In this study, we conducted complete molecular characterization of the somatostatin gene in Bubalus bubalis (Murrah breed) by sequencing a Murrah BAC clone spanning 72,489 base pairs (bp) in length. The buffalo somatostatin gene contains 1481 bp organized into a 5'-untranslated region (135 bp), exon 1 (139 bp), intron 1 (839 bp), exon 2 (212 bp), and 3'UTR (156 bp). Comparative analysis between the buffalo somatostatin DNA coding sequence and the amino acid sequence with other bovids (cattle, goat, and sheep), horse, pig, human, rodents (mouse and rat), and chicken. Identity varied from 83-99% on the DNA sequence level and 88-100% on the protein level. In addition, a comparison of gene sequences between Murrah and Mediterranean breeds revealed 6 potential single-nucleotide polymorphisms (1 in exon 1 and 5 in intron 1), which were validated in different buffalo populations. This comparative analysis provides basic information for future studies of different buffalo herds using the position candidate gene approach, quantitative trait loci analysis, and polymorphisms associated with growth traits.

Influence of the A and B subunits of cholera toxin (CT) and Escherichia coli toxin (LT) on TNF-alpha release from macrophages.

In this study an in vitro model was developed with the aim of investigating the modulatory effect of cholera toxin (CT) and its counterpart the heat labile toxin of Escherichia coli (LT) on TNF-alpha release induced by murine macrophages and primary human monocytes. Previous studies have demonstrated that the enzymatic activity of CT and LT molecules can inhibit TNF-alpha release by macrophages. The results obtained in this study showed that CT and LT are both, in a dose dependent manner, able either to induce or inhibit TNF-alpha release by murine macrophages and primary human monocytes. The results also showed that recombinant B subunits of CT and LT in the absence of their A subunit induce high levels of TNF-alpha release by macrophages and, in addition, increase the level of TNF-alpha release induced by LPS. The ability of both B subunits (CTB and LTB) in inducing TNF-alpha release by macrophages is not related to the level of LPS contamination, since direct measurements of LPS made in the samples employed in this study showed only traces of LPS (3.4 x 10(-8) EU/ml) which is in our system does not induce TNF-alpha release by macrophages. In contrast to the results obtained with the B subunits, incubation of cells with the A subunit of CT (CTA) inhibit TNF-alpha release induced by native CT, native LT, recombinant LTB and LPS. This inhibitory effect must be related to the activity of the A subunit since viability tests performed in terms of metabolic rate demonstrated that high concentrations of CTA are not toxic to the cells. The data presented herein demonstrate that the A subunits of CT and LT have an inhibitory effect on TNF-alpha release in macrophages, whereas their B subunits have a stimulatory effect on TNF-alpha. The results also suggest that the dose dependent bi-modal effect of native CT and native LT on TNF-alpha release by macrophages is a result of the combined effect of their individual A and B subunits.

Chronic alcohol consumption induces lipofuscin deposition in the rat hippocampus.

Previous investigations have suggested that chronic alcohol consumption accelerates a number of age-related changes in the cerebellar cortex and hippocampal formation. In the cerebellum, alcohol-feeding has been shown to accelerate the intracellular deposition of lipofuscin. In order to determine whether alcohol administration has a similar effect on hippocampal lipofuscin deposition, we studied the pattern of lipofuscin deposition in alcohol-fed rats for periods of 1, 3, 6, 12 and 18 months and compared the results with those obtained in the respective pair-fed controls. A precocious and progressive deposition of lipofuscin pigment was found in both CA1 and CA3 neurons in Ammon's horn hippocampal fields after 3 and 6 months of alcohol feeding, respectively. These results parallel those observed during normal aging and reinforce the hypothesis of a close link between chronic alcohol consumption and a premature nerve cell aging.

Gamma-IFN and macrophage respiratory burst in Calomys callosus challenged with Trypanosoma cruzi bloodstream and metacyclic forms.

Parasitemia levels of Calomys callosus inoculated with a high dose (HBT) of 4 x 10(3) Trypanosoma cruzi strain M226 bloodstream trypomastigotes (BT) exceeded those with the same inoculum of metacyclic trypomastigotes (MT) while a similar parasitemia was obtained with a low dose (LBT) of 5 x 10(2) of BT. Serum IFN-gamma levels during the acute phase of infection were higher in the LBT inoculated group when compared with the group inoculated with HBT, while the IFN-gamma levels in MT inoculated animals were close to uninfected controls. Spontaneous liberation of H2O2 of peritoneal macrophages explanted from animals on days 21 and 28 after infection was comparable to that of controls for HBT and LBT groups while that of the MT inoculated group was significantly higher. Phorbol Myristate Acetate (PMA) stimulation resulted in high H2O2 liberation specially in the infected groups. In vitro challenge with BT suppressed the small amount of spontaneous H2O2 release, while MT challenge stimulated this release to a limited degree in infected groups. In this animal model, interacting with a parasite strain isolated from the same host, macrophage activation as measured by H2O2 release was low, while the same strain had been previously observed to result in hyperactivation of mouse macrophages. We suggest that this distinctive behavior may be due to a host-parasite adaptation.

Prostaglandin and nitric oxide regulate TNF-alpha production during Trypanosoma cruzi infection.

The mechanisms that control TNF-alpha production by macrophages during Trypanosoma cruzi infection are still unknown. Destruction of intracellular forms by cytokine activated macrophages is considered to be a major mechanism of parasite elimination. Although in vitro TNF-alpha contributes to enhanced parasite destruction by macrophages, previous work in vivo has shown that as the parasite burden increases, serum TNF-alpha levels decline. In this report we show that TNF-alpha production by peritoneal adherent cells is elevated at the initial phase of T. cruzi infection. As infection progresses TNF-alpha production decreases. The observed reduction is partly due to inhibition, largely exerted by endogenous PG and secondarily by NO. Inhibition of their synthesis partially restored the ability to produce high levels of TNF-alpha to macrophages upon stimulation by LPS. Neither endogenous IL-10 nor TGF-beta seem to be involved in the negative regulation of TNF-alpha production.

Giant multivesicular bodies in the rat hippocampal pyramidal cells after chronic alcohol consumption.

Multivesicular bodies (MVBs) with diameters up to 4.5 microns were observed in the hippocampal pyramidal cells of rats submitted to chronic alcohol consumption. A significant increase in the volumetric density (Vv) of these organelles was found in CA1 pyramidal cells. Transitional forms of MVBs towards lysosomes were seen. A failure in MVB's enzymatic hydrolytic mechanisms, due to the prolonged alcohol aggression, could underlie its formation.

Reactivity of Trypanosoma cruzi strains with peanut agglutinin (PNA) correlates with number of in vitro infected host cells.

Reactivities of 4 lectins with intact trypomastigote forms derived from 8 different Trypanosoma cruzi strains were compared with their capacity to infect in vitro cultured LLC-MK(2)cells. A sensitive and reproducible titration method for lectin binding sites (ELLA: Enzyme Linked Lectin Assay) was employed, in which reactivities were scored through optical densities in an ELISA reader. Tissue culture trypomastigotes from the strains Y, CL, SC4, SC24, SC25, SC28, SC32 and SC33 were investigated for expression of different cell surface carbohydrate residues using Concanavalin A (ConA), Peanut agglutinin (PNA), Soybean agglutinin (SBA) and Wheat germ agglutinin (WGA) conjugated to peroxidase. The reactivity of the strains to PNA lectin was SC28 > SC32 > SC33 > SC25> SC24 > Y> CL> SC4. The optical density values obtained were highly correlated (r2=0.986, p< 10(-4)) with the number of parasitized LLC-MK(2) cells 24 hours after infection by trypomastigotes from each corresponding strain. We concluded that galactose and N-acetyl-D-galactosamine residues that are present on the surface of trypomastigotes are important in host-cell recognition.

Modulation of antibody response to sheep red blood cells by cyclophosphamide in Calomys callosus (Rodentia).

1. Calomys callosus, a wild rodent reservoir of Trypanosoma cruzi, notably resistant to laboratory infection with this parasite, is currently under study as a new experimental model for Chagas' disease. 2. To investigate the humoral immune response of C. callosus, rodents were injected with sheep red blood cells (SRBC) and the resulting antibody titers measured 0, 5, 9, 14, 20, 27 and 37 days later by the direct agglutination test. 3. Modulation of the antibody response by cyclophosphamide (Cy) was also studied, showing that the administration of 400 or 200 mg Cy/kg body weight one day prior to SRBC inoculation had an immunosuppressive effect. When the 200 mg/kg dose was given on day 0, antibody levels were significantly lower than those of controls on the 5th day after SRBC inoculation; subsequent differences were not statistically significant. 4. When SRBC were injected 5 or 10 days after Cy administration, the same effect was observed, indicating that the time of antigen inoculation is important in antibody modulation. A second dose of 200 mg Cy/kg on day 5 resulted in significant antibody suppression up to the 37th day. The administration of 20 mg Cy/kg resulted in a slight antibody enhancement seen on the 5th day after SRBC inoculation given on day 0. 5. These data demonstrate that cyclophosphamide modulates the T-dependent antibody response in C. callosus in a manner similar to the mouse model.

Modulation of parasitemia and antibody response to Trypanosoma cruzi by cyclophosphamide in Calomys callosus (Rodentia, Cricetidae).

Calomys callosus a wild rodent, previously described as harboring Trypanosoma cruzi, has a low susceptibility to infection by this protozoan. Experiments were designed to evaluate the contribution of the immune response to the resistance to T. cruzi infection exhibited by C. calossus. Animals were submitted to injections of high (200 mg/kg body weight) and low (20 mg/kg body weight) doses of cyclophosphamide on days -1 or -1 and +5, and inoculated with 4 x 10(3) T. cruzi on day O. Parasitemia, mortality and antibody response as measured by direct agglutination of trypomastigotes were observed. Two hundred mg doses of cyclophosphamide resulted in higher parasitemia and mortality as well as in suppression of the antibody response. A single dose of 20 mg enhanced antibody levels on the 20th day after infection, while an additional dose did not further increase antibody production. Parasitemia levels were not depressed, but rather increased in both these groups as compared to untreated controls. Passive transfer of hyperimmune C. callosus anti-T. cruzi serum to cyclophosphamide immunosuppressed animals resulted in lower parasitemia and mortality rates. These results indicate that the immune response plays an important role in the resistance of C. callossus to T. cruzi.

Regional variation in toxoplasmosis seronegativity in the São Paulo metropolitan region.

Toxoplasmosis is a highly prevalent zoonotic human infection caused by the Apicomplexa protozoon Toxoplasma gondii. The acute disease is usually mild or asymptomatic, except for foetal infection transmitted by acutely infected pregnant women, which courses as a devastating disease. In order to determine possible regional variations in risk factors, we studied the frequency of seronegativity in areas of the São Paulo Metropolitan Region, comparing titers and age groups. The prevalence of seronegativity was determined retrospectively in 1286 pregnant women receiving prenatal care at public health services in four selected areas of the São Paulo Metropolitan Region of similar socioeconomic background. The São Paulo City area had the higher frequency of seronegativity (41.1%), followed by the Northwest (31.5%) and Southwest (29.9%) areas, with similar intermediate levels, and by the Northeast (22.5%) area with the lowest frequency (p < 0.001). A rough estimate disclosed about 280 infected infants/year in the São Paulo Metropolitan Region. Serological titers analyzed by age group suggested a decline in antibody levels with age, as shown by a lower frequency of higher titers in older groups. Our study emphasizes the importance of determining the regional prevalence of toxoplasmosis for proper planning of public health prenatal care.