The Anti-Leukemia Effect of Ascorbic Acid: From the Pro-Oxidant Potential to the Epigenetic Role in Acute Myeloid Leukemia.

Data derived from high-throughput sequencing technologies have allowed a deeper understanding of the molecular landscape of Acute Myeloid Leukemia (AML), paving the way for the development of novel therapeutic options, with a higher efficacy and a lower toxicity than conventional chemotherapy. In the antileukemia drug development scenario, ascorbic acid, a natural compound also known as Vitamin C, has emerged for its potential anti-proliferative and pro-apoptotic activities on leukemic cells. However, the role of ascorbic acid (vitamin C) in the treatment of AML has been debated for decades. Mechanistic insight into its role in many biological processes and, especially, in epigenetic regulation has provided the rationale for the use of this agent as a novel anti-leukemia therapy in AML. Acting as a co-factor for 2-oxoglutarate-dependent dioxygenases (2-OGDDs), ascorbic acid is involved in the epigenetic regulations through the control of TET (ten-eleven translocation) enzymes, epigenetic master regulators with a critical role in aberrant hematopoiesis and leukemogenesis. In line with this discovery, great interest has been emerging for the clinical testing of this drug targeting leukemia epigenome. Besides its role in epigenetics, ascorbic acid is also a pivotal regulator of many physiological processes in human, particularly in the antioxidant cellular response, being able to scavenge reactive oxygen species (ROS) to prevent DNA damage and other effects involved in cancer transformation. Thus, for this wide spectrum of biological activities, ascorbic acid possesses some pharmacologic properties attractive for anti-leukemia therapy. The present review outlines the evidence and mechanism of ascorbic acid in leukemogenesis and its therapeutic potential in AML. With the growing evidence derived from the literature on situations in which the use of ascorbate may be beneficial in vitro and in vivo, we will finally discuss how these insights could be included into the rational design of future clinical trials.

Inclusive K(S);(0)K(S);(0) resonance production in ep collisions at HERA.

Inclusive K_{S};{0}K_{S};{0} production in ep collisions at the DESY ep collider HERA was studied with the ZEUS detector using an integrated luminosity of 0.5 fb;{-1}. Enhancements in the mass spectrum were observed and are attributed to the production of f_{2}(1270)/a_{2};{0}(1320), f_{2};{'}(1525) and f_{0}(1710). Masses and widths were obtained using a fit which takes into account theoretical predictions based on SU(3) symmetry arguments, and are consistent with the Particle Data Group values. The f_{0}(1710) state, which has a mass consistent with a glueball candidate, was observed with a statistical significance of 5 standard deviations. However, if this state is the same as that seen in gammagamma-->K_{S};{0}K_{S};{0}, it is unlikely to be a pure glueball state.

Shuttle walking test and 6-minute walking test induce a similar cardiorespiratory performance in patients recovering from an acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: The incremental shuttle walking test (SWT) has recently been proposed as a more valid and reproducible alternative to the conventional 6-min walking test (6MWT) in the evaluation of exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: To compare the cardiorespiratory performance obtained during two sessions of SWT with that obtained during two sessions of 6MWT. METHODS: We examined 18 patients (forced expiratory volume in 1 s: 48 +/- 14%) recovering from an acute exacerbation of COPD that had required hospitalization. In the same afternoon, each patient performed two SWT and two 6MWT, with an interval of at least 30 min between each test; the sequence of the tests was randomized. RESULTS: Mean walking distance was greater in the second SWT test than in the first SWT. The changes from baseline in systolic blood pressure, heart rate, respiratory rate, oxygen saturation and dyspnea Borg index at the end of the test were similar between the two 6MWT and the two SWT. There was a highly significant correlation between walking distances measured during SWT and during 6MWT (rho: 0.85, p < 0.0005). Neither SWT nor 6MWT correlated with functional data of COPD. CONCLUSIONS: SWT, though being considered to be closer to a submaximal exercise test than 6MWT, does not induce a greater cardiorespiratory performance than 6MWT in patients recovering from acute exacerbation of COPD.

[Polyarticular heterotopic ossification complicating drug induced coma]. / Ossificazione polidistrettuale eterotopica conseguente a coma controllato.

The Authors describe a case of generalised heterotopic ossification (HO) complicating the course of a 31 years old male patient, with a history of Hodgkin's lymphoma and a of long staying in an intensive care unit, where he had been placed on artificial coma. The clinical features, as well as radiological findings and therapy, are discussed.

Polyarticular heterotopic ossification complicating drug-induced coma.

The authors describe a case of generalised heterotopic ossification (HO) complicating the clinical course of a 31-year-old male patient with a history of Hodgkin's lymphoma and of long stay in an intensive care unit, where he had been placed in an artificial coma. The clinical features, as well as radiological findings and therapy, are discussed.

Alternate modes of binding in two crystal structures of alkaline phosphatase-inhibitor complexes.

Two high resolution crystal structures of Escherichia coli alkaline phosphatase (AP) in the presence of phosphonate inhibitors are reported. The phosphonate compounds, phosphonoacetic acid (PAA) and mercaptomethylphosphonic acid (MMP), bind competitively to AP with dissociation constants of 5.5 and 0.6 mM, respectively. The structures of the complexes of AP with PAA and MMP were refined at high resolution to crystallographic R-values of 19.0 and 17.5%, respectively. Refinement of the AP-inhibitor complexes was carried out using X-PLOR. The final round of refinement was done using SHELXL-97. Crystallographic analyses of the inhibitor complexes reveal different binding modes for the two phosphonate compounds. The significant difference in binding constants can be attributed to these alternative binding modes observed in the high resolution X-ray structures. The phosphinyl group of PAA coordinates to the active site zinc ions in a manner similar to the competitive inhibitor and product inorganic phosphate. In contrast, MMP binds with its phosphonate moiety directed toward solvent. Both enzyme-inhibitor complexes exhibit close contacts, one of which has the chemical and geometrical potential to be considered an unconventional hydrogen bond of the type C-H...X.

[Registry of genetic and malformative diseases in the province of Macerata]. / Registro delle malattie genetiche e malformative della provincia di Macerata.

OBJECTIVES: The aim of this epidemiological research is to evaluate the prevalence of genetic diseases and malformative syndromes in paediatric population living in the Macerata county. MATERIAL AND METHODS: All the data were collected through a careful analysis of a specific questionnaire sent to all the family paediatricians. RESULTS: 23,379 children living in Macerata county, aged 0 to 9 years, were evaluated (93.8% of all this paediatric population). Among those were found N 400 cases of genetic diseases and malformative syndromes: Malformations Tot.N. 255 cases (63.3% of the reported cases); Malformative Syndromes Tot. N. 55 cases (27.8% of the reported cases); Endocrinology and Metabolic Diseases Tot. N. 41 cases (10.3% of the reported cases); Osteochondrodysplasia Tot. N. 22 cases (5.7% of the reported cases); Other Tot. N. 28 cases (7.0% of the reported cases); Male population was found more affected than female: M/F ratio = 1.4. The analysis of the data showed an increasing trend in detecting these pathological conditions, consistent with the increase in geographic altitude (3 areas considered): 0-100 meter = 0.88%; 100-600 m.a.s. = 1.34%; over 600 m.a.s. = 1.88%. CONCLUSION: The knowledge of the number of children affected by genetic and malformative diseases in the Macerata county is relevant in order to establish a Genetic Service with the aim to better support the medical assistance of these patients and counselling service for the families.

[A case of atrial myxoma with connectivitis-like onset]. / Un caso di mixoma atriale ad esordio similconnettivitico.

A case of cardiac myxoma is reported. This tumor, although histologically benign, may be potentially lethal if an early diagnosis and an adequate surgical treatment is not performed. In an early stage, the disease may be asymptomatic or a large array of aspecific symptoms may be present. In this case, an initial diagnosis of polymyositis was made. This paraneoplastic syndrome is frequently associated with tumors, and should trigger a full evaluation for cancer.

[Septicemia and systemic inflammatory response]. / Setticemia e risposta infiammatoria sistemica.

To determine the relation between endocarditis/septicemia and systemic inflammatory response syndrome (SIRS), septic shock, MODS, we performed a retrospective analysis in 196 HIV-negative patients, with endocarditis/septicemia. No deaths were observed between 20 patients with endocarditis without severe infective SIRS/septic shock. On the other hand among 10 patients with endocarditis with severe infective SIRS/septic shock we registered 3 deaths (P = 0.052). No deaths were registered among 93 patients with septicemia without severe infective SIRS/septic shock. Between 73 patients with septicemia and severe infective SIRS/septic shock 9 (12.3%) patients died and, precisely, 7/61 in severe infective SIRS (11.4%) and 2/.12 (16.6%) in septic shock (P = 0.003). The definition of septicemia according to Schottmüller (1914), as a generalized bacterial infection with a persistent bacteremia is still justified. The term "sepsis" has become ambiguous because it has been used as synonym of "acute response to infection", while in the past and presently, at least in Europe, it is synonym of septicemia, persistent bacteremia. The term of SIRS could avoid the misunderstanding. The words: "infective SIRS", "severe infective SIRS", may label properly the reactive events mounted by the host as a useful defence against infections but they become dangerous and bring about septic shock, organ failure and mortality when excessive.

Risk factors for acute parenterally transmitted viral hepatitis: a 20-year study.

In order to verify the relative role of each single risk factor during a long period of observation, and to compare the frequency of risk factors in parenterally and non-parenterally transmitted acute viral hepatitis, we studied 1,251 patients admitted to our Department from 1971 to 1991. Acute hepatitis A cases were considered non-parenterally transmitted, whereas B, C, NANB and Delta hepatitis were grouped together as parenterally transmitted. The two groups were compared for age, sex and the following risk factors: surgical procedures, transfusion, dental procedures, intravenous drug addiction, infected partner, infected relative and hospital admission. There were 243 non-parenterally transmitted and 1,008 parenterally transmitted cases. In univariate analysis, mean age in the two groups was 20 and 37 years (p = 0.000001) for non-parenterally and parenterally transmitted cases respectively; mean ages of patients with different parenterally transmitted hepatitis (B, NANB, C, Delta) did not differ significantly (p = 0.35). The following risk factors were significantly more frequent in the parenterally transmitted hepatitis group: surgical procedure (odds ratio = 8.04, 95% confidence intervals: 3.75, 20.51), transfusion (OR = 18.79, 95% CI: 5.03, 157.72), dental procedures (OR = 2.19, 95% CI: 1.2, 4.06), drug addiction (OR: 11.02, 95% CI: 4.15, 41.34), and infected partner (OR = 17.61, CI: 3.02, 708.65). However, logistic regression showed the following factors as being significant: age (p = 0.00001), transfusion (OR = 3.35, 95% CI: 1.61, 6.94), dental procedures (OR = 1.61, 95% CI: 1.18, 2.2), drug addiction (OR = 4.88, 95% CI: 2.94, 8.1).(ABSTRACT TRUNCATED AT 250 WORDS)

[Study on the presence of Cryptosporidium in Umbria]. / Indagine sulla presenza del cryptosporidium in Umbria.

Cryptosporidium is an intestinal protozoan parasite belonging to the same family as Isospora and Toxoplasma. Cryptosporidium can cause severe, life-threatening enteritis in immunocompromised patients; he can also cause much less severe diarrhea in immunocompetent humans and in several animal species. Cryptosporidiosis has been diagnosed by identification of characteristic cocysts in fecal smear. In order to detect the small numbers of oocysts excreted, a modified Teleman-Miyagawa concentration technique was used. After, the faecal smears were stained by means of the dimethyl-sulfoxide (DMSO) acid-fast method. During 12 months, 157 specimens of faeces of patients with diarrhoea and 75 stool samples of asymptomatic humans were examined. Cryptosporidium was identified, only, in 2 of 157 stools of patients with diarrhoea. These two patients were less than 2 years of age. Cryptosporidial oocysts not were seen in the faeces of 75 asymptomatic humans and of 35 (only 20 with diarrhoea) immunocompromised patients. Failure to detect the agent in immunosuppressed patients in likely related to poor number of examinated cases. In conclusion, routine laboratory studies to identify Cryptosporidium in the stools of immunocompromised patients seem justified, since the parasite causes in these patients severe opportunistic also extra-intestinal infections.