Search

Patients with mucopolysaccharidosis type VI (MPS VI) present with a wide range of disease severity and clinical manifestations, with significant functional impairment and shortened lifespan. Enzyme replacement therapy (ERT) with galsulfase has been shown to improve clinical and biochemical parameters including patient survival, quality of life and growth. The present study is a resurvey of 34 Brazilian MPS VI patients with rapidly progressive disease (classical phenotype) who initiated ERT with galsulfase under five years of age and had been on ERT until data collection in 2019, with few exceptions (n = 4 patients who died before 2019). Anthropometric measures, urinary glycosaminoglycans, and data regarding cardiac, orthopedic, neurologic, sleep apnea, hearing and ophthalmologic outcomes were filled in by specialists. Pubertal development, clinical complications, hospitalizations, and surgeries were also assessed. In this resurvey study, treatment with galsulfase has shown to be safe and well tolerated in MPS VI patients who initiated ERT under the age of 5 years and who have been undergoing ERT for approximately 10 years. Mortality rate suggests that early initiation of ERT may have a positive impact on patients' survival, improving but not preventing disease progression and death. MPS VI patients on ERT also showed improved growth velocity and the pubertal development was normal in all surviving patients. Follow-up data on pneumonia and hospitalization suggest that early ERT may have a protective effect against major respiratory complications. Cardiac valve disease progressed since their prior evaluation and spinal cord compression was observed in a large number of patients, suggesting that these disease complications were not modified by ERT.

Ethnopharmacological relevance The stem barks of Zanthoxylum rhoifolium Lam. (Rutaceae), locally known as “mamica de cadela”, are popularly used in dyspepsies, stomachic, tonic, antitumoral, antipyretic and are used in treating flatulence and colic. The objective of this study was to evaluate the gastroprotective effect of the ethanolic extract of Zanthoxylum rhoifolium (EEZR) stem barks in acute gastric lesion models, investigating their possible mechanisms. Materials and methods Mice were used for the evaluation of the acute toxicity, and mice and rats to study the gastroprotective activity. The gastroprotective action of EEZR was analyzed in the absolute ethanol, HCl/ethanol and indomethacin-induced gastric lesion models in mice, hypothermic-restraint stress, and ischemia/reperfusion in rats. In the investigation of the gastroprotective mechanisms of EEZR, the participation of the NO-synthase pathway, ATP-sensitive potassium channels (K ATP ), the levels of the non-protein sulfhydril groups (NP-SH) and the catalase activity using the ethanol-induced gastric mucosa lesion model and the quantification of the gastric mucus and the antisecretory activity through pylorus ligature model in rats were analyzed. Results The animals did not present any signs of acute toxicity for the EEZR (up to the 4 g/kg dose, po), and it was not possible to calculate the DL 50 . EEZR (125–500 mg/kg) exhibited a significant gastroprotective effect in absolute ethanol, HCl/ethanol, hypothermic-restraint stress, and ischemia/reperfusion-induced gastric lesion models. EEZR (250 and 500 mg/kg) exhibited still a gastroprotective activity in the indomethacin-induced ulcer model. Gastroprotection of EEZR was significantly decreased in pre-treated mice with l -NAME or glibenclamide, the respective nitric oxide synthase and K ATP channels inhibitors. Our studies revealed that EEZR (500 mg/kg) prevented the decrease of the non-protein sulfhydril groups (NP-SH) and increased the catalase levels in ethanol-treated animals. Furthermore, the extract (500 mg/kg) significantly increased the mucus production, however, the gastric secretion parameters (volume, [H + ], pH) did not show any alteration. Conclusions Our results indicate that the ethanolic extract of Zanthoxylum rhoifolium exhibits a significant gastroprotection, because it inhibits the formation of gastric lesions using different models. The release of the nitric oxide, the opening of the K ATP channels, the participation of the non-protein sulfhydril groups (NP-SH), catalase and the increase of mucous secretion seem to be involved in the gastroprotection activity of the EEZR. Nevertheless, this activity does not seem to be related to antisecretory mechanisms.

This study assesses the antinociceptive effect induced by different dosages of topiramate (TP), an anticonvulsant drug that is orally administered in models of neuropathic pain and acute pain in rats and mice, respectively. Orally administered TP (80 mg/Kg) in mice causes antinociception in the first and second phases of a formalin test, while in doses of 20 and 40 mg/Kg it was only effective in the second phase. TP (80 mg/Kg, p.o) also exhibited antinociceptive action in the hot plate test, however, it did not have an effect in the capsaicin test in mice, nor in the model of neuropathic pain in diabetic rats. The antinociceptive effect caused by TP (80 mg/Kg, p.o) in the formalin test was reversed by prior treatment with naloxone (opioid antagonist), but not with glibenclamide (antagonist of the potassium channel), ondansetron (antagonist of the serotonin 5HT3 receptor) or cyproheptadine (antagonist of the serotonin 5HT2A receptor).The data show that TP has an important antinociceptive effect in the models of nociception induced by chemical (formalin) or thermal (hot plate) stimuli, and that the opioid system plays a part in the antinociceptive effect, as shown by formalin.

Methods: The study was done with 37 patients at National Cancer Institute, Brazil, from May 2012 to February 2013. The data collected were: age, gender and PG-SGA at the time of admission. Circulating T lymphocytes (CD4, CD8, NKT like) and Natural Killer (NK) cells were evaluated by threecolor flow cytometry immunophenotyping. Data were acquired using the CellQuest software (BD Biosciences) and analyzed with the Infinicyt software (Cytognos). The statistical analysis was performed using SPSS 17.0, using the Student t test and Pearson correlation, considering p < 0.05 as statistically significant. Results: Among the patients studied, 62.2% were male, 64.9% were elderly, 29.7% were considered well nourished (A), 51.4% considered moderate malnourished or with malnutrition risk (B) and 18.9% severely malnourished (C), with PG-SGA score range from 1 to 31. Regarding the initial immune profile, all the parameters were considered normal and there was no statistical difference between groups (table 1). However, there was a negative correlation between PG-SGA score and CD4 (r = 0.48, p = 0.01).

Ethnopharmacological relevance Lecythis pisonis Camb., also known in Brazil as sapucaia, is used in folk medicine against pruritus, muscle pain and gastric ulcer. Aim of the study To investigate the antinociceptive effect of ethanol extract from Lecythis pisonis leaves (LPEE), fractions (hexane-LPHF, ether-LPEF and ethyl acetate-LPEAF) and mixture of triterpenes [ursolic and oleanolic acids (MT)] in mice. Materials and methods LPEE and LPEF were evaluated on the acetic acid induced writhings and formalin, capsaicin and glutamate tests. In addition, MT was investigated on the writhings induced by acetic acid, capsaicin and glutamate tests. In the study of some possible mechanisms involved on the antinociceptive effect of LPEF, it was investigated the participation of opioid system, K+ATP channels and l -arginine-nitric oxide pathway. Results LPEE (12.5 and 25 mg/kg, p.o.), LPEF and MT (6.25, 12.5 and 25 mg/kg, p.o.) reduced the writhings in comparison to saline. LPEE (100 mg/kg, p.o.) and LPEF (50 mg/kg, p.o.) were effective in inhibiting both phases of formalin test. In capsaicin test, LPEE (100 and 200 mg/kg, p.o.), LPEF (12.5–50 mg/kg, p.o) and MT (6.25–25 mg/kg, p.o.) showed a significant antinociceptive effect compared to the control. LPEE (25 and 50 mg/kg, p.o.), LPEF (50 and 100 mg/kg, p.o.) and MT (12.5 and 25 mg/kg, p.o.) reduced the glutamate-evoked nociceptive response. Treatment with naloxone, l -arginine and glibenclamide reversed the effect of LPEF in glutamate test. Conclusions These results indicate the antinociceptive effect of Lecythis pisonis leaves and suggest that this effect may be related to opioid pathway, K+ATP channels, and l -arginine-nitric oxide modulation. Furthermore, these data support the ethnomedical use of this plant.