Aminoguanidine impedes human pancreatic tumor growth and metastasis development in nude mice

AIM： To study the action of aminoguanidine on pancreatic cancer xenografts in relation to cell proliferation, apoptosis, redox status and vascularization. METHODS： Xenografts of PANC-1 cells were developed in nude mice. The animals were separated into two groups： control and aminoguanidine treated. Tumor growth, survival and appearance of metastases were determined in vivo in both groups. Tumors were excised and ex vivo histochemical studies were performed. Cell growth was assessed by Ki-67 expression. Apoptosis was studied by intratumoral expression of B cell lymphoma-2 protein （Bcl-2） family proteins and Terminal deoxynucleotidyl transferase biotin-dUTP Nick End Labeling （Tunel）. Redox status was evaluated by the expression of endothelial nitric oxide synthase （eNOS）, catalase, copper-zinc superoxide dismutase （CuZnSOD）,manganese superoxide dismutase （MnSOD） and glutathione peroxidase （GPx）. Finally, vascularization was determined by Massons trichromic staining, and by VEGF and CD34 expression. RESULTS： Tumor volumes after 32 d of treatment by aminoguanidine （AG） were significantly lower than in control mice （P 〈 0.01）. Median survival of AG mice was significantly greater than control animals （P 〈 0.01）. The appearance of both homolateral and contralateral palpable metastases was significantly delayed in AG group. Apoptotic cells, intratumoral vascularization （trichromic stain） and the expression of Ki-67, Bax, eNOS, CD34, VEGF, catalase, CuZnSOD and MnSOD were diminished in AG treated mice （P 〈 0.01）, while the expression of Bcl-2 and GPx did not change. CONCLUSION： The antitumoral action of aminoguanidine is associated with decreased cell proliferation, reduced angiogenesis, and reduced expression of antioxidant enzymes.     

Classification of anemia for gastroenterologists

Most anemia is related to the digestive system by dietary deficiency, malabsorption, or chronic bleeding. We review the World Health Organization definition of anemia, its morphological classification （microcytic, macrocytic and normocytic） and pathogenic classification （regenerative and hypo regenerative）, and integration of these classifications. Interpretation of laboratory tests is included, from the simplest （blood count, routine biochemistry） to the more specific （iron metabolism, vitamin B12, folic acid, reticulocytes, erythropoietin, bone marrow examination and Schilling test）, in the text and various algorithms, we propose a hierarchical and logical way to reach a diagnosis as quickly as possible, by properly managing the medical interview, physical examination, appropriate laboratory tests, bone marrow examination, and other complementary tests. The prevalence is emphasized in all sections so that the gastroenterologist can direct the diagnosis to the most common diseases, although the tables also include rare diseases. Digestive diseases potentially causing anemia have been studied in preference, but other causes of anemia have been included in the text and tables. Primitive hematological diseases that cause anemia are only listed, but are not discussed in depth. The last section is dedicated to simplifying all items discussed above, using practical rules to guide diagnosis and medical care with the greatest economy of resources and time.     

Outcomes of a Peritoneal Dialysis Program in Remote Communities Within Colombia

♦ Background and Objective: Colombia is a country of diverse geographic regions, some with mountainous terrain that can make access to urban areas difficult for individuals who live in remote areas. In 2005, a program was initiated to establish remote peritoneal dialysis (PD) centers in Colombia to improve access to PD for patients with end-stage renal disease who face geographic or financial access barriers.♦ Patients and Methods: The present study was a multi-center cohort observational study of prevalent home PD patients who were at least 18 years of age and were being managed by one of nine established remote PD centers in Colombia over a 2-year period. Data were collected from clinical records, databases, and patient interviews. Patient survival, incidence of peritonitis, and rate of withdrawal from PD therapy were assessed.♦ Results: A total of 345 patients were eligible for the study. The majority (87.8%) of patients lived on one to two times a minimum monthly salary (equivalent to US$243 – US$486). On average, patients traveled 1.2 hours and 4.3 hours from their home to their remote PD center or an urban reference renal clinic, respectively. The incidence rate of peritonitis was 2.54 episodes per 100 patient-months of therapy. A bivariate analysis showed a significantly higher risk of peritonitis in patients who were living on less than one times a monthly minimum salary (p < 0.05) or who had a dirt, cement, or unfinished wood floor (p < 0.05). The 1-year and 2-year patient survival rates were 92.44% and 81.55%, respectively. The 1-year and 2-year technique survival rates were 97.27% and 89.78%, respectively.♦ Conclusions: With the support of remote PD centers that mitigate geographic and financial barriers to healthcare, home PD therapy is a safe and appropriate treatment option for patients who live in remote areas in Colombia.     

Demonstration of the Burkitt's lymphoma Epstein-Barr virus phenotype in dividing latently infected memory cells in vivo

Epstein-Barr virus (EBV) is a herpesvirus that establishes a lifelong, persistent infection. It was first discovered in the tumor Burkitt's lymphoma (BL). Despite intensive study, the role of EBV in BL remains enigmatic. One striking feature of the tumor is the unique pattern of viral latent protein expression, which is restricted to EBV-encoded nuclear antigen (EBNA) 1. EBNA1 is required to maintain the viral genome but is not recognized by cytotoxic T cells. Consequently, it was proposed that this expression pattern was used by latently infected B cells in vivo. This would be the site of long-term, persistent infection by the virus and, by implication, the progenitor of BL. We now know that EBV persists in memory B cells in the peripheral blood and that BL is a tumor of memory cells. However, a normal B cell expressing EBNA1 alone has been elusive. Here we show that most infected cells in the blood express no detectable latent mRNA or proteins. The exception is that when infected cells divide they express EBNA1 only. This is the first detection of the BL viral phenotype in a normal, infected B cell in vivo. It suggests that BL may be a tumor of a latently infected memory B cell that is stuck proliferating because it is a tumor and, therefore, constitutively expressing only EBNA1.     

La fragilidad en candidatos a trasplante renal

Frailty is a concept that has been mainly developed in geriatrics and it came from the need of identifying subjects at risk to develop complications when they faced a stressful event. Frail patients have higher risk of mortality, poor outcomes and disability, and this is independent from their age or comorbidities. Chronic kidney disease patients present with high prevalence of frailty, especially those who are in renal replacement therapy. Frail or pre-frail patients on the kidney transplant waiting list represent 20-30%, and these patients are proven to have poorer results after the transplant, which is a stressful event itself. Tools for frailty assessment, both scales or indexes, may be useful to identify which subjects might be at risk for complications after transplant, and this is necessary to adapt our clinical practice and minimize morbidity. The most used frailty scale in kidney patients is Fried scale, which is based in five phenotypic items. Besides that, knowing frail population allows potential interventions such as prehabilitation while the patient is waiting for the kidney transplant, which the aim of improving their vulnerability prior to transplant and, therefore, optimizing results after transplant. More studies are needed amongst kidney patients to improve and prevent frailty.     

Anti-Inflammatory and Antioxidant Activities of Methanol Extracts and Alkaloid Fractions of Four Mexican Medicinal Plants of Solanaceae

Background

Methanol extracts and alkaloid fractions of different parts of four plant species belonging to Solanaceae family and used in Mexican traditional medicine were investigated for their total phenolic contents, anti-inflammatory and antioxidant properties.

Materials and Methods

The total phenolic compounds of each extract was determined according to the Folin-Ciocalteu method, while the in vitro radical scavenging activities of the extracts were assessed using the DPPH and ABTS radicals. The in vivo anti-inflammatory activity was determined using the TPA-induced mouse ear edema model.

Results

The methanol extracts contained the highest concentrations of phenolic compounds and also exhibited the best reducing power on the DPPH and ABTS radicals, in a concentration-dependent fashion. However, the anti-inflammatory activity did not follow the same trend, as some alkaloid fractions that showed low radical reducing power exhibited the strongest anti-inflammatory activity.

Conclusion

The methanol extract obtained from the flowers of Nicotiana glauca presented the best overall performance with the largest amount of phenolic compounds (111 µg garlic acid equivalents/g of extract), the best antioxidant activity (94.80% inhibition of DPPH and 97.57% of ABTS) and the highest anti-inflammatory activity (81.93% inhibition of the inflammation).