Increased expression of matrix metalloproteinases 2 and 9 as poor prognosis factor for Hodgkin's lymphoma patients

Abstract Objective: The aim of our study was to evaluate the expression of MMP-2 and MMP-9 as a prognostic factor in patients diagnosed with Hodgkin Lymphoma (HL). Methods: In the present study, 45 paraffin biopsies from patients up to 19 years old diagnosed with HL were used in two referral hospitals in the state of Pernambuco, Brazil. Risk groups were classified into favorable and unfavorable, according to Ann Arbor. The expression of matrix metalloproteinases 2 and 9 and their inhibitors was performed by immunohistochemistry (IHC). Data were analyzed using the GraphPad Prism 5 program. Results: MMP-2 intensity pattern was stronger (> 10% of the total field) in patients with stage III/ IV and B symptoms. MMP-2 showed an association with the risk group (p = 0.0388). That is, the stronger the MMP-2 marking, the greater the unfavorable risk. However, for MMP-9 there was no difference in the stronger intensity pattern in relation to stages I/II and III/IV, only in the presence of B symptoms. MMP-9 showed an association with B Symptoms (p = 0.0411). Therefore, patients with B symptoms have higher MMP-9 expression. Conclusion: Our results suggest that MMP-2 expression is associated with HL progression. While MMP-9 expression is related to the clinical worsening of these patients. However, further studies are needed to evaluate the exact role of these proteins in hematologic malignancies.

Increased expression of matrix metalloproteinases 2 and 9 as poor prognosis factor for Hodgkin's lymphoma patients.

OBJECTIVE: The aim of our study was to evaluate the expression of MMP-2 and MMP-9 as a prognostic factor in patients diagnosed with Hodgkin Lymphoma (HL). METHODS: In the present study, 45 paraffin biopsies from patients up to 19 years old diagnosed with HL were used in two referral hospitals in the state of Pernambuco, Brazil. Risk groups were classified into favorable and unfavorable, according to Ann Arbor. The expression of matrix metalloproteinases 2 and 9 and their inhibitors was performed by immunohistochemistry (IHC). Data were analyzed using the GraphPad Prism 5 program. RESULTS: MMP-2 intensity pattern was stronger (>10% of the total field) in patients with stage III/IV and B symptoms. MMP-2 showed an association with the risk group (p = 0.0388). That is, the stronger the MMP-2 marking, the greater the unfavorable risk. However, for MMP-9 there was no difference in the stronger intensity pattern in relation to stages I/II and III/IV, only in the presence of B symptoms. MMP-9 showed an association with B Symptoms (p = 0.0411). Therefore, patients with B symptoms have higher MMP-9 expression. CONCLUSION: Our results suggest that MMP-2 expression is associated with HL progression. While MMP-9 expression is related to the clinical worsening of these patients. However, further studies are needed to evaluate the exact role of these proteins in hematologic malignancies.

Repeated-doses and reproductive toxicity studies of the monoterpene 1,8-cineole (eucalyptol) in Wistar rats.

1,8-cineole (eucalyptol) is widely used as an excipient in the pharmaceutical industry and as a food flavoring agent, thus providing significant potential for human exposure to the compound. We investigated the preclinical toxicity and reproductive toxicity of 1,8-cineole (CIN). In the repeated-doses toxicity study for 50 days, CIN (100, 500 or 1000 mg/kg) did not produce any signs of toxicity or deaths, but affected body weight gain during the first week of treatment. The hematological and biochemical profiles did not show significant differences except for increase in the MCV, platelet and urea levels or reduction in MCHC, MPV and alkaline phosphatase. Histopathological analysis showed weak changes in the lungs, liver, kidneys and uterus. In the reproductive toxicity, CIN (250, 500 or 1000 mg/kg) produced a reduction in body weight in pregnant rats treated during the pre-implantation or organogenesis periods. The highest doses induced a reduction in the mass of fetuses (pre-implantation) and dead fetuses (both periods) of pregnant rats. The results indicate that the treatment by repeated-doses showed occasional alterations in rats of both sexes. However, provide evidence that possibly 1,8-cineole presents maternal and fetal toxicity. This requires more detailed investigation to better characterize the toxic effects of this compound.

Gastroprotective Mechanisms of the Monoterpene 1,8-Cineole (Eucalyptol).

Recently, our research group identified and reported 1,8-cineole (CIN), a monoterpene that naturally occur in many aromatic plants, as one of the major constituent of the essential oil from leaves of Hyptis martiusii (EOHM), as well as characterized the gastroprotective action of this oil. The aim of this study was to investigate the mechanisms of action involved in the antiulcer and healing activity of CIN, in order to confirm its correlation with the gastroprotective effect of EOHM. Wistar rats were exposed to different protocols (acute ulceration, gastrointestinal motility and antisecretory activity). In addition, were determinated the involvement of nitric oxide and sulphydryl groups; the levels of gastric mucus, lipid peroxidation, sulphydryl groups and myeloperoxidase activity. The healing ability was evaluated by acetic acid-induced chronic ulcer and histological and immunohistochemical analysis (PCNA, Ki-67 and BrdU). The treatment with CIN inhibited ethanol-, ethanol/HCl- and indomethacin-induced gastric lesions. The highest doses of CIN inhibited gastric emptying, but did not affect intestinal transit. CIN (100 mg/kg) reduced the volume of basal but not stimulated acid secretion. CIN increased levels of mucus (89.3%), prevented depletion of -SH groups (62.6%) and reduced the level of lipid peroxidation (55.3%) and myeloperoxidase activity (59.4%) in the gastric mucosa. In chronic ulcer model, CIN reduced in 43.1% the gastric area lesion, promoted significant regeneration and restoration of the levels of mucus in glandular cells as confirmed by histological analysis; and promoted increase in cell proliferation as evidenced by reactivity for PCNA, Ki-67 and BrdU. This findings demonstrate the role of 1,8-cineole as an important ulcer healing agent and indicate the involvement of antioxidant and cytoprotective mechanisms in the gastroprotective effect of compound. This study also provides evidence that 1,8-cineole is related to the gastroprotective effect of the essential oil of Hyptis martiusii.

Infection by multidrug-resistant Elizabethkingia meningoseptica: case reports / Infecção por Elizabethkingia meningoseptica multirresistente: relato de casos

We report two cases of sepsis in critically ill patients in two tertiary care hospitals in Recife-PE, Brazil. The first case is an 87-year-old patient with chronic myeloid leukemia and sepsis; and the second case is a 93-year-old patient with prostate cancer and septic shock caused by multidrug-resistant (MDR) Elizabethkingia meningoseptica.

Reportamos dois casos de sepse em pacientes criticamente debilitados em dois hospitais com nível de complexidade terciária em Recife-PE, Brasil. O primeiro caso, paciente de 87 anos com leucemia mieloide crônica e sepse; o segundo, paciente com 93 anos de idade com câncer de próstata apresentava choque séptico causado por Elizabethkingia meningoseptica multirresistente.

Repeated-Doses Toxicity Study of the Essential Oil of Hyptis martiusii Benth. (Lamiaceae) in Swiss Mice.

Hyptis martiusii Benth. (Lamiaceae) is found in abundance in Northeastern Brazil where it is used in traditional medicine to treat gastric disorders. Since there are no studies reporting the toxicity and safety profile of this species, we investigated repeated-doses toxicity of the essential oil of Hyptis martiusii (EOHM). Swiss mice of both sexes were orally treated with EOHM (100 and 500 mg/kg) for 30 days, and biochemical, hematological, and morphological parameters were determined. No toxicity signs or deaths were recorded during the treatment with EOHM. The body weight gain was not affected, but there was an occasional variation in water and food consumption among mice of both sexes treated with both doses. The hematological and biochemical profiles did not show significant differences except for a decrease in the MCV and an increase in albumin, but these variations are within the limits described for the species. The microscopic analysis showed changes in liver, kidneys, lungs, and spleen; however, these changes do not have clinical relevance since they varied among the groups, including the control group. The results indicate that the treatment of repeated-doses with the essential oil of Hyptis martiusii showed low toxicity in mice.