Prednisone and prednisolone effects on development, blood, biochemical and histopathological markers of Aquarana catesbeianus tadpoles.

Synthetic glucocorticoids are often found in surface waters and can cause harmful effects to aquatic organisms such as amphibians. In this work we evaluated the effects of the drugs prednisone (PD) and prednisolone (PL) on developmental, molecular, blood, biochemical and histological markers. Aquarana catesbeianus tadpoles were exposed for 16 days to environmentally relevant concentrations of 0, 0.1, 1 and 10 µg/L of both drugs. PD increased the transcript levels of the enzyme deiodinase III (Dio3), the hormones cortisol and T4 and delayed development. Changes in the thyroid gland occurred after tadpoles were exposed to both drugs, with a reduction in the diameter and number of follicles and an increase/or decrease in area. Also, both drugs caused a decrease in lymphocytes (L) and an increase in neutrophils (N), thrombocytes, the N:L ratio and lobed and notched erythrocytes. Increased activity of the enzymes superoxide dismutase, glutathione S-transferase and glucose 6-phosphate dehydrogenase was observed after exposure to PD. Furthermore, both drugs caused an increase in the activity of the enzymes catalase and glutathione peroxidase. However, only PD caused oxidative stress in exposed tadpoles, evidenced by increased levels of malondialdehyde and carbonyl proteins. Both drugs caused an increase in inflammatory infiltrates, blood cells and melanomacrophages in the liver. Our results indicate that PD was more toxic than PL, affecting development and causing oxidative stress.

Chronic systemic corticosteroid therapy influences the development of pulp necrosis and experimental apical periodontitis, exacerbating the inflammatory process and bone resorption in rats.

AIM: The main aim of the study was to evaluate the inflammatory response and development of apical periodontitis in rats chronically treated with glucocorticoids. METHODOLOGY: Male Wistar rats (Rattus novergicus) were randomly divided into two groups: the experimental group, which was treated with prednisone (5 mg/kg/day) and a control group, which was administered saline solution for 30 days before induction of apical periodontitis, continuing until the day of euthanasia days 0, 7, 14 and 28 after injury induction. The mandibles were subjected to histological evaluation to determine the size of the lesion, was also performed for the presence and absence of pulp necrosis, bone resorption and micro abscesses, and histomorphometric analyses were performed based on the number of polymorphonuclear cells and mononuclear cells. Histochemical analysis was also performed to assess the percentage of collagen fibres and their typification, in addition to immunohistochemistry for the inflammatory markers interleukin IL-1ß, IL-6, TNF-α and TRAP. RESULTS: Despite after 7 days, there was no differences between groups, a significant increase in the root pulp necrosis (p = .001), micro-abscesses (p = .026) and the size of the apical lesion on the 14th day of treatment with prednisone (p = .008). On the same day, there was also an increase in the number of polymorphonuclear cells (p = .042) and cells immunostained for IL-1ß (p = .006), IL-6 (p < .001) and TRAP (p = .002) in animals treated with prednisone. The numbers of mononuclear cells also increase in 28 days (p = .025) and TNF-α ± increases in the prednisone group on the 7th day (p = .041). The prednisone group also showed a decrease in collagen after 14 (both type I [p = .041] and type III [p = .046]) and 28 type III (p = .002) days after the coronary opening. CONCLUSIONS: The glucocorticoids modified the development of experimental apical periodontitis induced in rats, causing an early increase in periapical bone resorption and pulp necrosis. These effects are associated with alterations in cytokine levels, in the inflammatory response and in collagen deposition, in the 14th day after injury induction.

ABVD and BEACOPP regimens' effects on fertility in young males with Hodgkin lymphoma.

PURPOSE: Considering the increased cancer patient survivorship, the focus is now on addressing the impacts of treatment on quality of life. In young people, altered reproductive function is a major issue and its effects in young males are largely neglected by novel research. To improve clinician awareness, we systematically reviewed side effects of chemotherapy for Hodgkin lymphoma (HL) in young males. METHODS: The review was prospectively registered (PROSPERO N. CRD42019122868). Three databases (Medline via PUBMED, SCOPUS, and Cochrane Library) were searched for studies featuring males aged 13-51-years who underwent chemotherapy for HL using ABVD (Adriamycin® (doxorubicin), bleomycin, vinblastine, and dacarbazine) or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) regimens. These chemotherapy regimens were compared against each other using sperm characteristics, FSH, and inhibin B levels to measure fertility levels. RESULTS: Data were extracted from five studies featuring 1344 patients. 6 months post-ABVD saw marked deterioration in sperm count, further reduced by more cycles (P = 0.05). Patients treated with BEACOPP rather than ABVD were more prone to oligospermia. Receiving fewer cycles of both regimens increased the likelihood of sperm production recovering. Patients treated with 6-8 cycles of BEACOPP did not recover spermiogenesis. CONCLUSIONS: ABVD and BEACOPP regimens significantly reduce fertility function to varying effects depending on treatment duration. ABVD temporarily causes significant reductions in male fertility, whereas BEACOPP's effects are more permanent. Therefore, clinicians should discuss fertility preservation with male patients receiving infertility-inducing gonadotoxic therapy. Further high-quality studies are required to more adequality describe the risk to fertility by chemotherapy.

Liquid biopsy based on small extracellular vesicles predicts chemotherapy response of canine multicentric lymphomas.

Lymphoma is the most common type of canine hematological malignancy where the multicentric (cMCL) form accounts for 75% of all cases. The standard treatment is the CHOP chemotherapy protocols that include cyclophosphamide, doxorubicin, vincristine and prednisone, where the majority of dogs achieve complete/partial response; however, it is very important to predict non-responsive cases to improve treatment and to develop new targeted therapies. Here we evaluate a liquid biopsy approach based on serum Small Extracellular Vesicles enriched for exosomes (SEVs) to predict cMCL chemotherapy response. Nineteen dogs at the end of the 19-week chemotherapy protocol (8 Complete Response and 11 Progressive Disease) were evaluated for serum SEVs size, concentration and screened for 95 oncomirs. PD patients had higher SEVs concentration at the diagnosis than CR patients (P = 0.034). The ROC curve was significant for SEVs concentration to predict the response to CHOP (AUC = 0.8011, P = 0.0287). A potential molecular signature based on oncomirs from SEVs (caf-miR-205, caf-miR-222, caf-mir-20a and caf-miR-93) is proposed. To the best of our knowledge, this is the first study demonstrating the potential of a liquid biopsy based on SEVs and their miRNAs content to predict the outcome of chemotherapy for canine multicentric lymphomas.

An Open-label Study With Pirfenidone on Chronic Hypersensitivity Pneumonitis.

BACKGROUND: Chronic hypersensitivity pneumonitis (cHP) represents a severe lung disease often evolving to fibrosis with the subsequent destruction of the lung parenchyma. There are no approved therapies with confirmed efficacy to deal with this disease. METHODS: We performed an open-label, proof of concept study, to evaluate the efficacy and safety of pirfenidone added to immunosuppressive drugs on the treatment of cHP. We included 22 patients assigned to two groups: Group 1, nine patients that received prednisone plus azathioprine and Group 2, thirteen patients, received prednisone plus azathioprine and pirfenidone (ClinicalTrials.gov identifier NCT02496182). There were no significant imbalances in clinically relevant baseline characteristics between two study groups. RESULTS: After 1 year of treatment, inclusion of pirfenidone was not associated with improved forced vital capacity (primary end-point). A not significant tendency to show higher improvement of diffusion capacity of the lung for carbon monoxide (DLCO) was observed in the group receiving pirfenidone (p=0.06). Likewise, a significant improvement in the total score on the SGRQ was found in the group 2 (p=0.02) without differences in other two questionnaires related to quality of life (ATAQ-IPF and EQ-5D-3L). HRCT showed a decrease of the ground glass attenuation without changes in the fibrotic lesions and without differences between both groups. CONCLUSIONS: These findings suggest that the addition of pirfenidone to the anti-inflammatory treatment in patients with chronic HP may improve the outcome with acceptable safety profile. However, prospective randomized double-blind, placebo-controlled trials in largest cohorts are needed to validate its efficacy.

Diagnostic value of the dual-luciferase report assay for predicting response to glucocorticoid in children with acute lymphoblastic leukemia.

OBJECTIVE: Resistance to glucocorticoid (GC) is a significant clinical problem in some cases of acute lymphoblastic leukemia (ALL). Current methods of assessing GC resistance are time consuming and have limited reproducibility; in this study, we sought to define a new method of evaluating GC sensitivity and resistance in vitro. METHODS: Based on the mechanisms of GC resistance, we hypothesized that the dual-luciferase report (DLR) assay could reflect the transcription effects of GC downstream of the GC-glucocorticoid receptor signaling pathway, thereby allowing the evaluation of reactions to GC. Sixty-two patients with differential GC response were included in this study. The prednisone induction test was used to divide the children with ALL into two groups: GC sensitive (GCS) and GC resistant (GCR). DLR assay was later conducted on those patients to evaluate its value for diagnosis of the GC reactivity. Receiver operating characteristic curves were used to identify the optimal assay cutoff for identifying response to GC. RESULTS: Using the DLR assay analysis, we found that GCR subjects showed significantly lower reporter/control ratios for luciferase, as compared with GCS subjects. The optimal cutoff value for GC response was 0.67, with sensitivity of 77.1% and specificity of 93.3%. The DLR assay results were consistent with prednisone induction test results. Further, the DLR assay was simpler, more sensitive, and less time-consuming than the prednisone induction test. CONCLUSIONS: Our study showed that the DLR assay is relatively fast, simple, and sensitive. Accordingly, it could be useful for detecting GC response in children with ALL.

An innovative, simple, fast, and less toxic high-performance liquid chromatographic method for determination of prednisone in capsules

ABSTRACT Prednisone is an anti-inflammatory steroid drug widely used in clinical practice. However, no high-performance liquid chromatographic (HPLC) method has been described in the literature for the determination of prednisone in capsules until now. Thus, an HPLC method was developed using a C18 (250x4.0, 5 µm) column, with methanol:water (70:30) as mobile phase at a flow rate of 1 mL/min and detection at 240 nm. The developed method was validated following current Brazilian legislation. Additionally, linearity was assessed by evaluating the assumptions of normality, homoscedasticity, and independency of residuals, and the fit to the linear model. The method showed linearity (r2>0.99) over the range of 14.0-26.0 µg/mL, selectivity, precision (RSD<2.0%), robustness, and accuracy (average recovery of 100.05%). The chromatographic procedure was applied for assay and uniformity content determination of three different batches of prednisone capsules, showing to be suitable for their quality control.

Fitofotodermatite por Ruta graveolens com manifestação cutânea extensa / Phytophotodermatitis due to Ruta graveolens with extensive cutaneous manifestation

Dermatite de contato por planta ou fitodermatite é uma erupção cutânea resultante do contato com substâncias produzidas por diferentes espécies de vegetais. Ruta graveolens, popularmente conhecida como arruda, é uma planta da família das Rutaceae, que inclui algumas frutas cítricas, e contém inúmeras substâncias químicas fotossensíveis, incluindo os furocumarínicos. Relatamos um caso de reação de fitofototoxicidade grave em uma paciente que usou uma infusão de arruda pelas supostas qualidades ”místicas e purificadoras” da planta com extensa erupção cutânea.

Plant dermatitis or phytodermatitis is a cutaneous eruption resulting from contact with substances produced by different plant species. Ruta graveolens, popular known as common rue, is an herbal plant from the Rutaceae family, which includes the citrus fruits, and contains numerous photosensitizing substances, including furocoumarins. We report a severe case of phytophototoxicity reaction in a patient who used a common rue infusion because of its “powerful and purification” qualities.

Effects of immunosuppressive drugs on gastrointestinal transit of rats: effects of tacrolimus, cyclosporine, and prednisone.

Triple immunosuppressive therapy after organ transplantation may cause several gastrointestinal disturbances. It is difficult to identify which drug causes more complications, requiring an appropriate animal model. The aim was to compare the gastrointestinal transit in immunosuppressed rats under triple immunosuppressive therapy. Male rats were immunosuppressed by gavage during 14 days with tacrolimus (n = 10), cyclosporine (n = 12), and prednisone (n = 9). Animals received a magnetic pellet before (control) and after treatment that was monitored at predetermined intervals by AC biosusceptometry, a noninvasive and radiation-free technique. The following parameters were measured: creatinine serum, mean time of gastric emptying (MGET), mean time to reach cecum (MCAT), and mean transit time through small bowel (MSBTT). The differences were analyzed by ANOVA (Tukey). Our results showed that MGET of animals treated with prednisone, cyclosporine, and tacrolimus were reduced compared with control subjects (P < .03, P < .009, and P < .002, respectively). There was no difference in MCAT, whereas MSBTT was longer for tacrolimus and prednisone compared with control subjects (P < .004 and P < .004, respectively). Also, prednisone and tacrolimus presented a reduced MGET (P < .05 and P < .01, respectively) compared with cyclosporine. Our data showed a low serum creatinine level and no difference among groups regarding renal function. In summary, cyclosporine has less effect on the gastrointestinal transit; however, all of these drugs should be carefully prescribed to prevent gastrointestinal symptoms and improve quality of life after transplantation.

Randomized, controlled trial of budesonide and prednisone for the treatment of idiopathic inflammatory bowel disease in dogs.

BACKGROUND: Budesonide has been used to treat inflammatory bowel disease (IBD) in dogs, but no controlled studies have been performed to evaluate efficacy of this treatment. OBJECTIVE: To compare budesonide and prednisone for induction therapy of IBD in dogs by using IBD activity index scores and evaluating frequency and severity of owner-reported adverse effects. ANIMALS: Forty client-owned dogs with newly diagnosed idiopathic IBD were enrolled between April 2001 and January 2004; 34 dogs completed the 6 week study. METHODS: Double-blinded, randomized controlled trial. Dogs were randomized to receive either pure powder-based budesonide (3-7 kg: 1 mg PO q24h, 7.1-15 kg: 2 mg PO q24h, 15.1-30 kg: 3 mg PO q24h, >30 kg: 5 mg PO q24h) for 6 weeks or prednisone (1 mg/kg PO q12h × 3 weeks then 0.5 mg/kg PO q12h × 3 weeks). IBD activity index (IBDAI) scores were determined at diagnosis and after 6 weeks of treatment. Pet owners completed weekly questionnaires regarding clinical signs and incidence and severity of adverse effects. RESULTS: Significant differences in remission rates (>75% decrease in IBDAI scores) were not observed with a remission rate of 78% in the budesonide group and 69% in the prednisone group (P = .70). Frequency of adverse effects was similar between the 2 groups. CONCLUSIONS AND CLINICAL IMPORTANCE: There was no demonstrable difference in remission rates or incidence of adverse effects between prednisone and budesonide for induction therapy of IBD in dogs.

Infusão contínua de morfina ou fentanil, associados à lidocaína e cetamina, em cães anestesiados com isofluorano / Continuous infusion of morphine or fentanyl, associated to lidocaine and ketamine, in isofluorane-anesthetized dogs

A técnica de analgesia multimodal, por meio da infusão contínua de fármacos, pode ser empregada para diminuir a incidência de sensibilização central durante a anestesia. Avaliaram-se as características cardiorrespiratórias, durante o procedimento de artroscopia de joelho, em cães anestesiados com isofluorano e monitorados por meio do índice biespectral, submetidos à infusão contínua de morfina ou fentanil, associada à lidocaína e cetamina. Utilizaram-se 16 cães adultos, machos ou fêmeas, os quais foram distribuídos aleatoriamente em dois grupos, denominados MLK - que recebeu morfina (3,3μg/kg/min), lidocaína (50μg/kg/min) e cetamina (10μg/kg/min) ou FLK - em que foi substituída a morfina pelo fentanil (0,03μg/kg/min). Os cães foram pré-tratados com levomepromazina (0,5mg/kg IV), induzidos à anestesia com propofol (5mg/kg) e mantidos com isofluorano, ajustando-se a concentração para obterem-se valores de índice biespectral entre 55 e 65. As mensurações da frequência cardíaca (FC), dos parâmetros eletrocardiográficos (ECG), das pressões arteriais sistólica (PAS), diastólica (PAD) e média (PAM), da tensão de dióxido de carbono expirado (EtCO2), da saturação de oxi-hemoglobina (SpO2), da frequência respiratória (FR) e da temperatura esofágica (T) iniciaram-se 30 minutos após a indução (M0) e continuaram após o início da infusão das soluções, em intervalos de 15 minutos (M15 a M75). Diferenças entre os grupos foram registradas para duração do complexo QRS (M60), para FC e T, entre M30 e M75, com MLK apresentando médias maiores que FLK, que registrou médias maiores que MLK para a SpO2 (M60), para os intervalos QT (M30 e M75) e RR (M0, M60 e M75). Concluiu-se que o emprego de morfina ou fentanil, associados à lidocaína e cetamina, promove efeitos semelhantes e não compromete as características avaliadas.

The multimodal analgesia technique by continuous infusion of drugs can be used to decrease central sensitization during anesthesia. Cardiorespiratory parameters in isofluorane-anesthetized dogs during joint arthroscopy were evaluated. For this, 16 adult mongrel dogs were randomly divided into two groups, named MLK (morphine (3.3mg/kg/min), lidocaine (50μg/kg/min) and ketamine (10mg/kg/min)) or FLK (replacing morphine by fentanyl (0.03mg/kg/min). Levomepromazine (0.5mg/kg IV) was used as a preanesthetic medication, and propofol (5mg/kg IV) was used for induction and isoflurane was used for maintained general anesthesia, allowing the bispectral index to be maintained between 55 and 65. The measurements of heart rate (HR), eletrocardiographic, systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures, end-tidal carbon dioxide partial pressure (ETCO2), pulse oxygen saturation (SpO2) respiratory rate (RR) and esophageal temperature (T) were performed 30 minutes after induction (M0), and after the infusion of solutions, at 15 minute intervals (M15 to M75). Differences between groups were registered for the duration of the QRS complex (M60), for HR and T (from M30 to M75), with MLK recording a higher mean than FLK, which registered a lower value than MLK for SpO2 (M60), QT (M30 and M75) and RR (M0, M60 and M75) intervals. It was concluded that morphine or fentanyl, associated with lidocaine and ketamine, promotes similar effects and does not impair the parameters evaluated.

Infusão contínua de morfina ou fentanil, associados à lidocaína e cetamina, em cães anestesiados com isofluorano / Continuous infusion of morphine or fentanyl, associated to lidocaine and ketamine, in isofluorane-anesthetized dogs

A técnica de analgesia multimodal, por meio da infusão contínua de fármacos, pode ser empregada para diminuir a incidência de sensibilização central durante a anestesia. Avaliaram-se as características cardiorrespiratórias, durante o procedimento de artroscopia de joelho, em cães anestesiados com isofluorano e monitorados por meio do índice biespectral, submetidos à infusão contínua de morfina ou fentanil, associada à lidocaína e cetamina. Utilizaram-se 16 cães adultos, machos ou fêmeas, os quais foram distribuídos aleatoriamente em dois grupos, denominados MLK - que recebeu morfina (3,3μg/kg/min), lidocaína (50μg/kg/min) e cetamina (10μg/kg/min) ou FLK - em que foi substituída a morfina pelo fentanil (0,03μg/kg/min). Os cães foram pré-tratados com levomepromazina (0,5mg/kg IV), induzidos à anestesia com propofol (5mg/kg) e mantidos com isofluorano, ajustando-se a concentração para obterem-se valores de índice biespectral entre 55 e 65. As mensurações da frequência cardíaca (FC), dos parâmetros eletrocardiográficos (ECG), das pressões arteriais sistólica (PAS), diastólica (PAD) e média (PAM), da tensão de dióxido de carbono expirado (EtCO2), da saturação de oxi-hemoglobina (SpO2), da frequência respiratória (FR) e da temperatura esofágica (T) iniciaram-se 30 minutos após a indução (M0) e continuaram após o início da infusão das soluções, em intervalos de 15 minutos (M15 a M75). Diferenças entre os grupos foram registradas para duração do complexo QRS (M60), para FC e T, entre M30 e M75, com MLK apresentando médias maiores que FLK, que registrou médias maiores que MLK para a SpO2 (M60), para os intervalos QT (M30 e M75) e RR (M0, M60 e M75). Concluiu-se que o emprego de morfina ou fentanil, associados à lidocaína e cetamina, promove efeitos semelhantes e não compromete as características avaliadas.(AU)

The multimodal analgesia technique by continuous infusion of drugs can be used to decrease central sensitization during anesthesia. Cardiorespiratory parameters in isofluorane-anesthetized dogs during joint arthroscopy were evaluated. For this, 16 adult mongrel dogs were randomly divided into two groups, named MLK (morphine (3.3mg/kg/min), lidocaine (50μg/kg/min) and ketamine (10mg/kg/min)) or FLK (replacing morphine by fentanyl (0.03mg/kg/min). Levomepromazine (0.5mg/kg IV) was used as a preanesthetic medication, and propofol (5mg/kg IV) was used for induction and isoflurane was used for maintained general anesthesia, allowing the bispectral index to be maintained between 55 and 65. The measurements of heart rate (HR), eletrocardiographic, systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures, end-tidal carbon dioxide partial pressure (ETCO2), pulse oxygen saturation (SpO2) respiratory rate (RR) and esophageal temperature (T) were performed 30 minutes after induction (M0), and after the infusion of solutions, at 15 minute intervals (M15 to M75). Differences between groups were registered for the duration of the QRS complex (M60), for HR and T (from M30 to M75), with MLK recording a higher mean than FLK, which registered a lower value than MLK for SpO2 (M60), QT (M30 and M75) and RR (M0, M60 and M75) intervals. It was concluded that morphine or fentanyl, associated with lidocaine and ketamine, promotes similar effects and does not impair the parameters evaluated.(AU)

Effects of prednisone on mucociliary clearance in a murine model.

All transplant patients are at increased risk of developing pulmonary infections, a significant cause of morbidity and mortality. Immunosuppressants increase the incidence of lung infection by acting not only directly on the inflammatory cells, but also on the native immune system. Experimental studies have shown corticosteroid therapy, which is used in most immunosuppressive protocols after transplantation, to suppress mucus production by inhibiting calceiform. The objective of this study was to evaluate the effects of prednisone on mucociliary clearance. A total of 120 male Wistar rats were distributed into 4 groups. Animals in P1, P2, and P3 groups received daily doses of prednisone (0.625, 1.25, and 2.5 mg/kg/d), and hosts in the Sal group underwent gavage with saline solution (2.5 mL/d). After 7, 15, and 30 days, treatment, animals were killed. We assessed ciliary beating frequency (CBF), mucociliary transport velocity (MCTV), and mucus transportability (MT). There was no significant difference for CBF regarding dose (P = .089) or treatment duration (P = .175). MCTV values of 0.60 ± 0.14 in group P1, 0.59 ± 0.13 in group P2, 0.51 ± 0.19 in group P3, and 0.61 ± 0.08 Group Sal, showed P3 to significantly differ from P1 (P = .048) and Sal (P = .007) groups. Regardless of the prednisone dose, all groups displayed impaired MT compared with the Sal group: P1 (P = .02); P2 (P = .02) P3 (P = .03). There was no interaction between the therapy and the treatment time for CBF (P = .10), MCTV (P = .71), and MT (P = .64). Prednisone reduced the transportability of mucus even when administered at low doses; however, this change was not sufficient to alter the mucociliary clearance. Only high doses of prednisone impaired mucociliary clearance.

Predictive models for pulmonary function changes after radiotherapy for breast cancer and lymphoma.

PURPOSE: To propose multivariate predictive models for changes in pulmonary function tests (ΔPFTs) with respect to preradiotherapy (pre-RT) values in patients undergoing RT for breast cancer and lymphoma. METHODS AND MATERIALS: A prospective study was designed to measure ΔPFTs of patients undergoing RT. Sixty-six patients were included. Spirometry, lung capacity (measured by helium dilution), and diffusing capacity of carbon monoxide tests were used to measure lung function. Two lung definitions were considered: paired lung vs. irradiated lung (IL). Correlation analysis of dosimetric parameters (mean lung dose and the percentage of lung volume receiving more than a threshold dose) and ΔPFTs was carried out to find the best dosimetric predictor. Chemotherapy, age, smoking, and the selected dose-volume parameter were considered as single and interaction terms in a multivariate analysis. Stability of results was checked by bootstrapping. RESULTS: Both lung definitions proved to be similar. Modeling was carried out for IL. Acute and late damage showed the highest correlations with volumes irradiated above ~20 Gy (maximum R(2) = 0.28) and ~40 Gy (maximum R(2) = 0.21), respectively. RT alone induced a minor and transitory restrictive defect (p = 0.013). Doxorubicin-cyclophosphamide-paclitaxel (Taxol), when administered pre-RT, induced a late, large restrictive effect, independent of RT (p = 0.031). Bootstrap values confirmed the results. CONCLUSIONS: None of the dose-volume parameters was a perfect predictor of outcome. Thus, different predictor models for ΔPFTs were derived for the IL, which incorporated other nondosimetric parameters mainly through interaction terms. Late ΔPFTs seem to behave more serially than early ones. Large restrictive defects were demonstrated in patients pretreated with doxorubicin-cyclophosphamide-paclitaxel.

Tratamento clínico das reações da Hanseníase com repercussão neurológica – revisão histórica / Clinical treatment of leprosy reactions affecting nerves - historical review

Foi realizada uma busca na literatura sobre o tratamento da neuropatia da hanseníase durante episódios reacionais, no tocante às reações tipo 1 e tipo 2. O levantamento refere-se ao período 1976-2010. Foram consultadas as bases de dados LILAU, MEDLINE e LILACS. O enfoque principal foi o tratamento das reações hansênicas, com esteróides via oral empregado nos Programas de Controle da Hanseníase.

An extensive search on the treatment of leprosy reactions in nerves is presented. It covers almost four decades, from 1976 to 2010. The data bases screened were the LILAU, MEDLINE and LILACS. The focal point was to review the steroid treatment indication in the Leprosy Control Programs.

Impact of corticosteroids on late growth of radiofrequency lesions in infant pigs: histopathological and electroanatomical findings.

AIMS: Corticosteroids attenuate late growth of radiofrequency (RF) lesions in the thigh muscle of infant rats. We sought to assess the impact of these drugs on the late growth of RF lesions in immature swine myocardium and to determine the electroanatomical mapping (EAM) characteristics of these lesions. METHODS AND RESULTS: Radiofrequency (60°C; 60 s) lesions were created in the right atrium (n = 2) and ventricle (n = 2) of 14 piglets (age 65 days; weight 5 kg) and 3 adults. Piglets were divided into: controls (n = 7) and treated (n = 7), receiving hydrocortisone (10 mg/kg iv after RF) and prednisone (1 mg/kg/day) for 29 days. After 8 months, animals were sacrificed for histological analysis. In four piglets, endocardial and epicardial voltage EAM were performed. In infant groups, the dimensions of atrial (11 ± 5 vs. 13 ± 7 mm) and ventricular (12 ± 3 vs. 11 ± 3 mm) lesions were similar. In adults, atrial (6 ± 1 mm) and ventricular (6 ± 1 mm) lesions were smaller. In controls, ventricular lesions depicted dense fibrosis and multiple strands of fibrous tissue extending from the lesion into normal muscle. Treated piglets revealed scars exhibiting less dense fibrosis with predominance of fibroadipose tissue and less collagen proliferation. Large atrial and ventricular low-voltage areas corresponding to the macroscopic lesions were identified in all animals. CONCLUSION: Radiofrequency lesions in infant pigs reveal late growth and invasion of normal muscle by intense collagen proliferation. Corticosteroids do not prevent late enlargement of the lesions but modulate the fibrotic proliferation. The expressive growth of the lesion may generate low-voltage areas detectable by EAM.

Dermatomiositis: a propósito de 3 casos interesantes / Dermatomyositis: with regard to 3 interesting cases

Se presentan los casos de 3 pacientes atendidos en el Hospital Pediátrico Juan Manuel Márquez, 2 de las cuales presentaron como primeras manifestaciones debilidad en los miembros inferiores y artritis que dificultaba la marcha de forma progresiva. El tercer paciente presentaba lesiones escamosas en la piel, hipopigmentadas en la cara y los miembros, acompañadas de astenia y artritis de las rodillas. Se realizaron estudios para concluir el diagnóstico, incluida la biopsia de músculo. Se aplicaron los criterios para confirmar el diagnóstico de dermatomiositis y se excluyeron otras enfermedades según el cuadro clínico y los exámenes complementarios realizados. A los 2 primeros pacientes se les indicó tratamiento inmunomodulador con prednisona y metotrexato, y al tercer paciente se le indicó prednisona y azathioprina. Se observó una buena respuesta al tratamiento y control de la enfermedad. El primer paciente falleció a los 4 meses de tratamiento a causa de complicaciones (vasculitis intestinal y sepsis asociada al tratamiento quirúrgico). Los restantes pacientes se siguen actualmente por consulta (AU)

Authors present three patients seen in the Juan Manuel Márquez Children Hospital where two of them had as first manifestations weakness in lower extremities and arthritis provoking a progressive difficulty to walk. The third patient had skin squamous lesions with hypopigmentation in the case and limbs as well as asthenia and knee arthritis. To made the diagnosis studies were conducted including thigh biopsy Criteria were applied to confirm diagnosis of dermatomyositis with exclusion of other diseases according to clinical picture and complementary examinations performed. In the two first patients a imunomodulation treatment was prescribed including Prednisone and Methotrexate, and the other patient received Prednisone and Azathioprine. There was a good response to treatment and a disease control. The first patient dye at 4 months of treatment due to complications (intestinal vasculitis and surgical treatment associated-sepsis). Remainder patients are followed up in consultation (AU)

Bone demineralization in the lumbar spine of dogs submitted to prednisone therapy.

Glucocorticoids are drugs widely used in veterinary medicine; however, besides their clinical benefits, their use can trigger undesirable effects. A clinical trial was performed on eight healthy dogs with the intent of evaluating possible alterations in the bone mineral density after therapy with prednisone using a helical computed tomography. All animals received prednisone orally at a dose of 2 mg/kg of weight for 30 days. The bone mineral density was determined by obtaining the vertebral body radiodensity of the second lumbar vertebra values immediately before and after the administration of the medication. The experimental protocol allowed for the characterization of a significant (P < 0.01) reduction of the vertebral body radiodensity of the second lumbar vertebra. At the end of the experiment, it was characterized by a loss of bone mass of approximately 14%. None of the animals presented pathologic fracture at the end of the administration of the medication. This study verified that the alterations in the bone metabolism of the dogs submitted to the therapy with prednisone in a dosage of 2 mg/kg occur rapidly, which recommends a monitoring of the patients for the prevention of pathologic fractures.

Increased plasma myeloperoxidase levels in systemic lupus erythematosus.

The objective of the study was to quantify plasma myeloperoxidase (MPO) levels in systemic lupus erythematosus (SLE) patients and to evaluate a correlation between MPO levels and disease activity. 71 female SLE patients and 70 controls were studied. Patients were divided into two groups: Group I (n = 48) with SLEDAI-2K score 0-5 and Group II (n = 23) with SLEDAI-2K score > or = 6. Mann-Whitney test and Spearman rank correlation were used. Two-sided P values < 0.05 were considered significant and P values > or = 0.05 and < 0.08 were considered as a tendency. The median age of patients and controls were comparable and the mean disease duration was 99.2 +/- 61.7 months. MPO levels were higher in patients than controls [5.99 (4.38-8.64) vs. 5.00 (3.33-7.08) ng/ml, P = 0.02]. We did not find correlation between MPO levels and SLEDAI-2k (r = 0.07, P = 0.58). MPO levels were not affected by treatment with prednisone, cyclophosphamide or azathioprine, however, a tendency of lower levels was observed among patients under antimalarial drugs. There was no significant difference in MPO plasma levels between Group I and Group II (5.83 vs. 6.02 ng/ml, P = 0.99). MPO levels were higher in patients with arthritis than in those without arthritis (8.15 vs. 5.56 ng/ml, P = 0.010). No difference was observed among patients with and without other organs/systems involvement. SLE patients presented increased MPO plasma levels than healthy controls. Despite the lack of correlation between MPO plasma levels and disease activity, the higher MPO levels in patients with articular involvement suggests MPO may play a different role in the inflammatory process of some SLE manifestations.