Role of NT-proBNP and lung ultrasound in diagnosing and classifying heart failure in a hospitalized oldest-old population: a cross-sectional study.

AIM: Diagnosing and classifying heart failure (HF) in the oldest-old patients has technical and interpretation issues, especially in the acute setting. We assessed the usefulness of both N-terminal pro-brain natriuretic peptide (NT-proBNP) and lung ultrasound (LUS) for confirming HF diagnosis and predicting, among hospitalized HF patients, those with reduced ejection fraction (HFrEF). METHODS: We performed a cross-sectional study on 148 consecutive patients aged ≥ 80 years admitted to our Internal Medicine and Geriatrics ward with at least one symptom/sign compatible with HF and NT-proBNP ≥ 125 pg/mL. We measured serum NT-proBNP levels and performed LUS and transthoracic echocardiography (TTE) on admission before diuretic therapy. We divided our cohort into three subgroups according to the left ventricular ejection fraction (LVEF): reduced (LVEF ≤ 40%), mildly-reduced (LVEF = 41-49%) and preserved (LVEF ≥ 50%). RESULTS: The mean age was 88±5 years. Male prevalence was 42%. Patients with HFrEF were 19%. Clinical features and laboratory parameters did not differ between the three subgroups, except for higher NT-proBNP in HFrEF patients, which also had a higher number of total B-lines and intercostal spaces of pleural effusion at LUS. Overall, NT-proBNP showed an inverse correlation with LVEF (r = -0.22, p = 0.007) and a direct correlation with age, total pulmonary B-lines, and intercostal spaces of pleural effusion. According to the ROCs, NT-proBNP levels, pulmonary B-lines and pleural effusion extension were poorly predictive for HFrEF. The best-performing cut-offs were 9531 pg/mL for NT-proBNP (SP 0.70, SE 0.50), 13 for total B-lines (SP 0.69, SE 0.85) and one intercostal space for pleural effusion (SP 0.55, SE 0.89). Patients with admission NT-proBNP ≥ 9531 pg/mL had a 2-fold higher risk for HFrEF (OR 2.5, 95% CI 1.3-4.9), while we did not find any association for total B-lines ≥ 13 or pleural effusion ≥ 1 intercostal space with HFrEF. A significant association with HFrEF emerged for the combination of NT-proBNP ≥ 9531 pg/mL, total B-lines ≥ 13 and intercostal spaces of pleural effusion ≥ 1 (adjusted OR 4.3, 95% CI 1.5-12.9). CONCLUSIONS: Although NT-proBNP and LUS help diagnose HF, their accuracy in discriminating HFrEF from non-HFrEF was poor in our real-life clinical study on oldest-old hospitalized patients, making the use of TTE still necessary to distinguish HF phenotypes in this peculiar setting. These data require confirmation in more extensive and longer prospective studies.

An uncommon presentation of Wernicke-Korsakoff's syndrome in pregnancy: Case report.

Wernicke's encephalopathy is an acute neuropsychiatric syndrome resulting from severe thiamine (vitamin B1) deficiency. Symptoms occur with an acute onset and may vary according to the brain area involved. Altered consciousness is the most common clinical feature, together with ocular abnormalities and ataxia. We report the case of a pregnant women affected by pre-gestational hyperthyroidism that caused an uncommon presentation of Wernicke's encephalopathy. Symptoms differed from the classic triad and diagnosis was made possible by a thorough analysis of anamnestic factors and brain MRI. Alongside thiamine supplementation, a multidisciplinary approach which included physiokinesis and a phoniatric support was fundamental for the patient's recovery.

Current and Emerging Approaches for Pain Management in Hemophilic Arthropathy.

INTRODUCTION: Hemophilia is an inherited bleeding hematological disorder characterized by the partial or complete deficiency of clotting factor VIII or IX. Hemophilic arthropathy is the consequence of repeated joint bleeding (hemarthrosis) and its management is based on the prevention of acute bleeding through the administration of the deficient clotting factor concentrate or non-factor therapies. In addition, the management of acute and chronic pain is pivotal in hemophilic arthropathy in order to restore function and allow rehabilitation of the joint. METHODS: We conducted a qualitative review of the literature regarding current and emerging strategies for pain treatment in hemophilic arthropathy. This review considers systemic and local pharmacological and non-pharmacological interventions for acute and chronic pain management. RESULTS: In hemophilic arthropathy, pain management is based on analgesics such as paracetamol, which represents the first choice for acute and chronic pain in adults and children, in association with opioids for adults. Non-steroidal anti-inflammatory drugs inhibit platelet function, so that the currently preferred drugs are short courses of cyclooxygenase 2 inhibitors. Local treatment with intra-articular injections of corticosteroids is an option for refractory cases and physiotherapy has an important role after hemarthrosis and for the long-term management of chronic pain for both pediatric and adult patients. CONCLUSIONS: The management of pain in hemophilia requires more standardization. Meanwhile, the safest drugs should be used at the lowest effective dosage and for periods as short as possible. For the non-pharmacological management of pain in these patients, a multidisciplinary team including hematologists, orthopedic surgeons, rheumatologists, and physiotherapists is warranted.

Sobre cuidados em saúde em um hospital geral / Sobre cuidados de salud en un hospital general / About health care in a general hospital

Este artigo analisa práticas de cuidado em saúde vivenciadas em um hospital geral do Sistema Único de Saúde (SUS), com a intenção de problematizar e refletir sobre o cuidado e as práticas em saúde que se fazem presentes entre pessoas, no cotidiano do serviço, nas relações e nos fluxos que são estabelecidos. Utilizamos a Etnografia para descrever uma cena que reflete as relações entre os saberes, os cuidados e descuidados que se fazem em um hospital. Propomos pensar o cuidado como múltiplo e observamos o hospital por meio de sua constituição como uma "máquina de curar". Refletimos o encontro entre profissional e usuário, entre o cuidador e quem recebe o cuidado, para propor que em todo e qualquer encontro de saúde certo cuidado é realizado. (AU)

Este artículo analiza prácticas de cuidado de salud vividas en un hospital general del Sistema Único de Salud, con la intención de problematizar y reflexionar sobre el cuidado y las prácticas de salud presentes entre las personas, en el cotidiano del servicio, en las relaciones y en los flujos establecidos. Utilizamos la etnografía para describir una escena que refleja las relaciones entre los saberes, los cuidados y descuidados realizados en un hospital. Proponemos pensar el cuidado como múltiple y observamos el hospital a partir de su constitución como "máquina de curar". Reflejamos el encuentro entre profesional y usuario, entre el cuidador y quien recibe el cuidado, para proponer que en todos los encuentros de salud hay cierto cuidado que se realiza. (AU)

This article analyzes health care practices experienced in a general hospital of the Brazilian National Health System, with the intention of problematizing and reflecting on the care and health practices that are present among people, in the daily service, in the relationships and flows that are established. We use ethnography to describe a scene that reflects the relationship between knowledge, care and un-care practices that are performed in a hospital. We propose to think of care as multiple and we observe the hospital from its constitution as a "healing machine". We reflect the encounter between professional and user, between the caregiver and the one who receives the care, to propose that in any and all health meetings, certain care is performed. (AU)

Long-term effect of oxycodone/naloxone on the management of postoperative pain after hysterectomy: a randomized prospective study.

BACKGROUND: The analgesic efficacy of oxycodone prolonged-release (PR) combined with naloxone PR (OXN) in postoperative pain management is recognized, however, few studies have examined the efficacy of OXN on pain relief and bowel function following hysterectomy. This study compared the effect of OXN vs. standard treatment for post-operative pain management and bowel function following hysterectomy. METHODS: This randomized prospective study included 83 women who underwent laparoscopic/laparotomic hysterectomy. General anesthesia was induced by propofol (1.5-2 mg/kg), fentanyl (50-100 µg) and rocuronium (0.6-1 mg/kg) and maintained with sevoflurane (MAC 0.8-1) and fentanyl (1-2 µg/kg). Intraoperative analgesia was performed with ketorolac (30 mg), paracetamol (1 g) and morphine (0.1 mg/kg). Postoperative analgesia in the control group (N.=41) included morphine (0.2-0.4 mg/kg/day), whereas the OXN (N.=42) group only received oxycodone (10 mg)/naloxone (5 mg) for the first 48 hours. As rescue analgesic, both groups received paracetamol (3 mg). Bowel Function Index (BFI) and pain numeric rating scales (NRS) were measured at day 0, 1, 2, 3, 5 and 7, whereas vital parameters, rescue medication and side effects were recorded for the first three days only. RESULTS: Bowel function indices were significantly improved in OXN-treated patients at all time points compared to morphine-treated patients. Mean static pain NRS was significantly decreased at day 2 and day 3 and dynamic pain NRS at day 3 in the OXN group. Side effects, rescue analgesic and antiemetics were more frequent in the control group. CONCLUSIONS: Improved pain control, bowel function and reduced side effects were observed with OXN compared to morphine in patients who underwent hysterectomy.

Evaluation of Cerebrospinal Fluid Pressure by a Formula and Its Role in the Pathogenesis of Glaucoma.

PURPOSE: To investigate potential associations between intraocular pressure (IOP) and cerebrospinal fluid pressure (CSFP) in patients with primary open-angle glaucoma (POAG) and healthy subjects. METHODS: Forty-three subjects were recruited. Weight and height were measured to calculate body mass index (BMI), along with blood pressure, heart rate, visual acuity, and IOP. Biometrics exam, corneal pachymetry, peripapillary retinal nerve fiber layer (RNFL) thickness, and macular thickness were assessed. The visual field exam was performed on all patients, and both pattern standard deviation (PSD) and mean deviation (MD) were considered. CSFP was estimated indirectly by using the mathematical formula CSFP = 0.44 × BMI + 0.16 × diastolic pressure - 0.18 × age - 1.91, based on the previous scientific studies. The TLCPD was calculated as follows: IOP-CSFP. RESULTS: A significant (p < 0.05) difference was found between the two groups for several parameters. Specifically, the CSFP was lower in patients with POAG than in healthy subjects (8.14 ± 4.52 and 7.43 ± 2.06, p < 0.001, respectively). Anamnestic TLCPD was found to be significantly (p < 0.001) higher in patients with POAG compared to healthy subjects. A significant (p < 0.05) correlation was found between anamnestic TLCPD and MD (r = -0.31), inferior RNFL thickness (r = -0.29), superior RNFL thickness (r = -0.27), IOP (r = 0.22), and CSFP (r = -0.46). CONCLUSION: The CSFP was lower in glaucomatous patients compared to healthy subjects, whereas the TLCPD was higher in glaucomatous patients compared to healthy subjects, even though this difference was not statistically significant. A higher TLCPD may damage the RNFL, resulting in functional visual field impairment.

Acute Exacerbation of Chronic Obstructive Pulmonary Disease in Oldest Adults: Predictors of In-Hospital Mortality and Need for Post-acute Care.

OBJECTIVES: Older age is associated with higher risk of death during acute exacerbations of chronic obstructive pulmonary disease (AE-COPD). Older patients hospitalized for AE-COPD often require post-acute care after acute phase. The aim of this study was to evaluate components of a comprehensive geriatric assessment and clinical/laboratory parameters, in order to find predictors of in-hospital mortality and need for post-acute care in patients aged 80 and older hospitalized for AE-COPD. DESIGN: Prospective observational study. SETTING: Hospital assessment. PARTICIPANTS: 121 patients consecutively admitted to an internal medicine and geriatrics department for AE-COPD. MEASURES: Activities of Daily Living (ADL) Hierarchy scale, Geriatric Index of Comorbidity, cognitive impairment, and clinical and laboratory parameters were collected. RESULTS: Mean age: 87.0 ± 4.9 years; male: 54.5%. In-hospital mortality (18.2% of patients) was significantly associated with functional disability, high comorbidity, cognitive impairment, anemia, older age, lower albumin, higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) and white blood cell levels, oral corticosteroids taken before admission, and no angiotensin-converting enzyme inhibitors or angiotensin receptor blockers taken before admission. In a stepwise logistic regression, functional dependence (P = .006), cognitive impairment (P = .038), and oral corticosteroids therapy before hospitalization (P = .035) were independently associated with a higher risk of in-hospital mortality. Among laboratory parameters, only NT-proBNP remained significantly associated with in-hospital mortality (P = .026). The need for post-acute care (18.2% of survivors) was associated with older age, higher admission Pco2, greater comorbidity, and cognitive impairment. In a stepwise logistic regression, only cognitive impairment (P = .016) and ln_Pco2 (P = .056) confirmed their association with the need for post-acute care. CONCLUSIONS/IMPLICATIONS: Preadmission functional dependence, cognitive impairment, and corticosteroid use, plus elevated NT-proBNP at admission are risk factors for mortality during an AE-COPD in the oldest old. Therefore, medical providers should consider these, as well as the patient's advance directives, in planning hospital care. Furthermore, providers should arrange especially careful posthospitalization monitoring and frequent follow-up of individuals with cognitive impairment and baseline hypercapnia.

Does the Bursa Pre-Macularis protect the fovea from shear stress? A possible mechanical role.

Purpose of present study is to evaluate whether the Pre-Macular Bursa (PMB) modifies Wall Shear Stress (WSS) at the retinal surface during saccadic movements. We created a mathematical model consisting of 25,000 grid cells and simulated a horizontal saccade spanning 50° in 0.17s, both in absence and in presence of the PMB. Wall Shear Stress SS was computed throughout the retinal surface and the posterior pole was divided into 3 Zones comprising 400 nodes each: Zone 1 (radius 3.5 mm; 0°-17°) corresponding to the PMB area; Zone 2 (concentric annular area 5 mm in radius; 22°) and Zone 3 (concentric annular area 5.5 mm; 28°). The PMB reduced WSS significantly at the macula and increased it in the immediate surroundings. Average WSS in Zone 1 was 1.53 ±â€¯1.01 (max 4.23 Pa) with PMB Vs 6.94 ±â€¯9.23 (max 35.83 Pa) without. Zone 2 WSS was 9.39 ±â€¯10.33 (max 48.36 Pa) with PMB Vs 6.95 ±â€¯9.40 (max 38.60 Pa) without Zone 3 WSS was 8.41 ±â€¯10.03 (max 43.16 Pa) with PMB Vs 6.88 ±â€¯9.42 (max 39.43 Pa) without (p < 0.001 in all cases). The PMB significantly reduces WSS over the retinal surface underlying the bursa region; conversely, WSS slightly increases it in the immediate neighboring areas.

Combination Therapy of Inhaled Indacaterol/Glycopyrronium for Chronic Obstructive Pulmonary Disease in the Very Elderly: Is It Safe? An Electrocardiographic Evaluation.

Cardiovascular (CV) comorbidities in patients with chronic obstructive pulmonary disease (COPD) are associated with increased morbidity and mortality, especially in old and very old subjects. The question if long-acting beta-agonist and long-acting muscarinic antagonist could be associated with the increased prevalence of CV-related adverse effects has puzzled, particularly in the past, specialists involved in the management of respiratory diseases. The safety of these compounds has scarcely been tested in patients aged ≥ 65 years with CV comorbidities, since randomized controlled trials rarely include this subpopulation. However, the fixed combination indacaterol/glycopyrronium has shown a favorable CV safety profile in both healthy volunteers and COPD patients. Thus, we aimed to assess the CV safety pro-- file of the fixed combination indacaterol/glycopyrronium 110/50 µg in a series of COPD patients aged ≥ 80 years with several comorbidities. Our results indicate that this combination is safe in the comorbid elderly, since no significant electrocardiographic abnormalities were recorded after the administration of the inhaled therapy. Only rare and nonclinically significant changes in heart rate and corrected QT interval duration were evident, mainly in females and in patients with concomitant impaired kidney function.

Renin-Angiotensin System Blockers and Statins Are Associated With Lower In-Hospital Mortality in Very Elderly Hypertensives.

OBJECTIVES: Cardiovascular diseases are mainly related to hypertension and dyslipidemia and increase with aging because of the larger time span for these risk factors to damage arterial blood vessels. The impact of cardiovascular drug therapy on outcomes in the very elderly hospitalized is still not well established. The aim of our study was to evaluate the associations between cardiovascular therapy and in-hospital mortality in very elderly hypertensives. DESIGN: Prospective observational study. SETTING: Hospital assessment. PARTICIPANTS: 310 very elderly hypertensive patients admitted to our Internal Medicine and Geriatrics Department for medical conditions. MEASUREMENTS: Main comorbidities, laboratory parameters, and cardiovascular drug therapy taken before admission were considered for the analyses. RESULTS: The mean age was 88.1 ±â€¯5.1 years, with female prevalence of 57.4%. Among cardiovascular drugs taken before admission, angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers and statins were those associated with lower in-hospital mortality, even after adjusting for covariates (age, hemoglobin, albumin, acute kidney injury, ADL Hierarchy Scale, NT-proBNP levels) [odds ratio (OR) = 0.46, P = .045, and OR = 0.21, P = .008, respectively]. No difference regarding in-hospital mortality was found between ACE inhibitors and angiotensin receptor blockers (P = .414). CONCLUSION: ACE inhibitors/angiotensin receptor blockers and statins, through their beneficial effects on the cardiovascular system, have a positive impact on survival in very elderly hospitalized patients. Our data confirm the important role of such drugs even in this particular population with a mean age higher than 88 years, where scientific evidence is still scanty.

Ocular perfusion pressure control during pars plana vitrectomy: testing a novel device.

PURPOSE: To study the efficacy of a novel device intended to control infusion pressure based on mean ocular perfusion pressure (MOPP) during pars plana vitrectomy (PPV). METHODS: An arm blood pressure cuff connected to a vitrectomy machine calculated mean arterial pressure (MAP), while a pressure sensor close to the infusion trocar measured intraocular pressure (IOP). MOPP was calculated in real time in 36 consecutive patients undergoing PPV, who were divided into two groups. The device lowered IOP every time that calculated MOPP fell below 30 mmHg in the Control ON group (18 patients), while no action was taken in the Control OFF group (18 patients). RESULTS: Baseline IOP and blood pressure were similar between groups. The Control ON group had significantly lower average intraoperative IOP (30.5 ± 2.1 vs. 35.9 ± 6.9 mmHg; p = 0.002) and higher MOPP (56.4 ± 5.9 vs. 49.7 ± 6.1 mmHg) than the Control OFF group. The Control ON group also spent less time at MOPP < 10 mmHg and < 30 mmHg: 0 vs. 3.40 ± 2.38 min (p < 0.001) and 9.91 ± 7.15 vs. 16.13 ± 8.12 min (p = 0.02), respectively. CONCLUSIONS: The MOPP control device effectively maintained lower IOP and higher MOPP throughout surgery. It also helped avoid dangerous IOP peaks and MOPP dips, allowing patients to spend less time at MOPP of < 10 and < 30 mmHg.

Plasma renin activity to plasma aldosterone concentration ratio correlates with night-time and pulse pressures in essential hypertensive patients treated with angiotensin-converting enzyme inhibitors/AT1 blockers.

OBJECTIVES: Angiotensin-converting enzyme inhibitors (ACE-I) and AT1 blockers (ARB) are commonly used antihypertensive drugs, but several factors may affect their effectiveness. We evaluated the associations between ambulatory blood pressure (BP) monitoring (ABPM) parameters and plasma renin activity (PRA)-to-plasma aldosterone concentration (PAC) ratio (RAR) to test renin-angiotensin-aldosterone system inhibition in essential hypertensive patients treated with ACE-I or ARB for at least 12 months. METHODS: We evaluated 194 consecutive patients referred to our Hypertension Centre. ABPM, PRA and PAC tests were performed without any changes in drug therapy. RAR, PRA and PAC tertiles were considered for the analyses. RESULTS: Mean age: 57.4 ±â€Š12.0 years; male prevalence: 63.9%. No differences between RAR tertiles regarding the use of ACE-I or ARB (P = 0.385), as well as the other antihypertensive drug classes, were found. A reduction of all ABPM values considered (24-h BP, daytime BP and night-time BP and 24-h pulse pressure (PP), daytime PP and night-time PP) and a better BP control were observed at increasing RAR tertiles, with an odds ratio = 0.12 to be not controlled during night-time period for patients in the third tertile compared with patients in the first tertile (P < 0.001). This association remained significant even after adjusting for 24-h BP control. All the associations were also confirmed for PRA tertiles, but not for PAC tertiles. CONCLUSION: Higher RAR values indicate effective renin-angiotensin-aldosterone system inhibition and lower night-time and pulse pressures in real-life clinical practice. It could be a useful biomarker in the management of essential hypertensive patients treated with ACE-I or ARB.

Interarm blood pressure differences predict target organ damage in type 2 diabetes.

Patients with type 2 diabetes mellitus are at high risk for atherosclerotic disease, and proper blood pressure measurement is mandatory. The authors examined the prevalence of an interarm difference (IAD) in blood pressure and its association with cardiovascular risk factors and organ damage (nephropathy, retinopathy, left ventricular hypertrophy, and vascular damage) in a large diabetic population. A total of 800 consecutive patients with type 2 diabetes mellitus were evaluated with an automated simultaneous bilateral device (men: 422 [52.8%]; mean age: 68.1±12.2 years). Diabetic patients with systolic IAD ≥5 and systolic IAD ≥10 mm Hg showed an increased risk of having vascular damage (adjusted odds ratios: 1.73 and 2.49, respectively) and higher pulse pressure. IAD is highly prevalent in patients with diabetes, is associated with vascular damage, even for IAD ≥5 mm Hg, and should be accurately obtained to avoid underdiagnosis and undertreatment of hypertension.

Specific aquaporins facilitate Nox-produced hydrogen peroxide transport through plasma membrane in leukaemia cells.

In the last decade, the generation and the role of reactive oxygen species (ROS), particularly hydrogen peroxide, in cell signalling transduction pathways have been intensively studied, and it is now clear that an increase of ROS level affects cellular growth and proliferation pathways related to cancer development. Hydrogen peroxide (H2O2) has been long thought to permeate biological membranes by simple diffusion since recent evidence challenged this notion disclosing the role of aquaporin water channels (AQP) in mediating H2O2 transport across plasma membranes. We previously demonstrated that NAD(P)H oxidase (Nox)-generated ROS sustain glucose uptake and cellular proliferation in leukaemia cells. The aim of this study was to assess whether specific AQP isoforms can channel Nox-produced H2O2 across the plasma membrane of leukaemia cells affecting downstream pathways linked to cell proliferation. In this work, we demonstrate that AQP inhibition caused a decrease in intracellular ROS accumulation in leukaemia cells both when H2O2 was produced by Nox enzymes and when it was exogenously added. Furthermore, AQP8 overexpression or silencing resulted to modulate VEGF capacity of triggering an H2O2 intracellular level increase or decrease, respectively. Finally, we report that AQP8 is capable of increasing H2O2-induced phosphorylation of both PI3K and p38 MAPK and that AQP8 expression affected positively cell proliferation. Taken together, the results here reported indicate that AQP8 is able to modulate H2O2 transport through the plasma membrane affecting redox signalling linked to leukaemia cell proliferation.

Comparison of intravenous ketorolac with or without paracetamol in postoperative pain control following ambulatory surgery.

OBJECTIVE: The aim of this randomized, patient-blinded study was to compare efficacy and safety of oral paracetamol plus intra-venous (i.v.) ketorolac with i.v. ketorolac alone after ambulatory uterine evacuation. RESEARCH DESIGN AND METHODS: Women were randomly assigned to receive either oral paracetamol (1 g), in a melt-in-the mouth, without-water formulation plus ketorolac (30 mg i.v. once daily (o.d.)) or ketorolac (30 mg i.v. o.d.) as monotherapy. The mean duration of uterine evacuation was 11 minutes in the paracetamol + ketorolac group and 13 minutes in the ketorolac-only group. Paracetamol was administered 15 minutes before surgery, on discharge from hospital (mean 6 hours after surgery) and in the morning the day after surgery, while ketorolac was administered at the end of the surgical intervention. MAIN OUTCOME MEASURES: The numeric rating scale (NRS) was used by patients to rate their pain on an 11 point scale. RESULTS: Overall, 60 women received paracetamol plus ketorolac (group 1) and 60 ketorolac alone (group 2). There were significant differences in pain levels (NRS 0.92 and 2.08; p < 0.01) at T0 (when patients left the operating room 30 minutes after the end of surgery). At T1 (before discharge from hospital but before the next administration of paracetamol) there were no significant differences between NRS scores in the two groups (3.7 vs. 3.5, respectively, p = 0.3453). At T2 (in the morning after surgery; data collected by phone interview), following administration of the next dose of paracetamol, significant differences in pain scores were recorded (1.58 vs. 1.98; p = 0.01). Only a case of dizziness was reported in the paracetamol + ketorolac group, and no other unexpected adverse events were recorded. CONCLUSION: Despite the small sample size and the monocentric nature of the study being taken into account, this study suggests, for the first time to our knowledge, that oral paracetamol t.i.d. in combination with i.v. ketorolac o.d. is effective and well tolerated in the control of postoperative pain after ambulatory uterine evacuation.

Dietary phenolic acids act as effective antioxidants in membrane models and in cultured cells, exhibiting proapoptotic effects in leukaemia cells.

Caffeic, syringic, and protocatechuic acids are phenolic acids derived directly from food intake or come from the gut metabolism of polyphenols. In this study, the antioxidant activity of these compounds was at first evaluated in membrane models, where caffeic acid behaved as a very effective chain-breaking antioxidant, whereas syringic and protocatechuic acids were only retardants of lipid peroxidation. However, all three compounds acted as good scavengers of reactive species in cultured cells subjected to exogenous oxidative stress produced by low level of H(2)O(2). Many tumour cells are characterised by increased ROS levels compared with their noncancerous counterparts. Therefore, we investigated whether phenolic acids, at low concentrations, comparable to those present in human plasma, were able to decrease basal reactive species. Results show that phenolic acids reduced ROS in a leukaemia cell line (HEL), whereas no effect was observed in normal cells, such as HUVEC. The compounds exhibited no toxicity to normal cells while they decreased proliferation in leukaemia cells, inducing apoptosis. In the debate on optimal ROS-manipulating strategies in cancer therapy, our work in leukaemia cells supports the antioxidant ROS-depleting approach.

Antitumor activity and COMPARE analysis of bis-indole derivatives.

This paper reports the synthesis of new derivatives (formed by two indole systems separated by a central moiety) analogous of potent antitumor agents previously described. The activity of the bis-indoles bearing a pyridine core confirms the good result described in the previous paper and compound 4c was chosen for the first in vivo experiment (Hollow Fiber Assay). COMPARE analysis and structure-activity relationships were also considered. Contrary to data reported by other Authors, no correlations were found between antitumor activity and NQO1 induction.

Inhibition of trans-plasma membrane electron transport: a potential anti-leukemic strategy.

The recently demonstrated reliance of glycolytic cancer cells on trans-plasma membrane electron transport (tPMET) for survival raises the question of its suitability as a target for anticancer drug development. In this study, the effects of several new and known compounds on proliferation, tPMET activity and NAD(P)H intrinsic fluorescence in human myelogenous leukemic cell lines were investigated. The whole data confirm the importance of tPMET in leukemic cell survival and suggest this activity as a new potential anti-leukemic target.

Induction of apoptosis in a human leukemic cell line via reactive oxygen species modulation by antioxidants.

In the human acute myeloid leukemia cell line M07e, the growth factor interleukin-3 (IL-3) induces ROS formation, positively affecting Glut1-mediated glucose uptake and cell survival. The effect of IL-3 and exogenous hydrogen peroxide on cell viability seems to be mediated through inhibition of the cell death commitment, as shown by apoptotic markers such as caspase activities, apoptotic nuclei, and changes in the amount of proteins belonging to the Bcl-2 family. The pivotal role of ROS is confirmed using various antioxidants, such as EUK-134, ebselen, TEMPO, and hydroxylamine probe. In fact, these antioxidants, acting through different mechanisms, decrease glucose transport activity and cell proliferation activated by IL-3 or by low concentrations of hydrogen peroxide. Moreover, antioxidants foster programmed cell death commitment, as shown by the cited apoptotic parameters. EUK-134, a combined superoxide dismutase/catalase mimetic, opposes the effects of IL-3 and H(2)O(2), decreasing phosphorylation levels of signaling enzymes such as Akt, Src tyrosine kinase, and ERK. Results show that ROS production induced by IL-3 can protect leukemic cells from apoptosis, the effect being counteracted by antioxidants. This mechanism may play an important role in supporting acute myeloid leukemia treatment, thus representing a novel therapeutic strategy.