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We recently showed that the treatment with Resveratrol (RES) contrasts the effects of ageing on the skeletal muscle (SKM), reduces the appearance of tubular aggregates (TAs), and improves the fatigue resistance. Since fatigue resistance depends on the SKM capillary network, and RES has been described to improve vascularisation, we analysed the SKM capillarization in naturally age- ing C57BL/6J male mice, fed with 0.04% RES in the diet for 6months, which showed a better fatigue resistance in a previous work. Our data show an inverse correlation between the number of capillaries per fibre (CAF) and TAs in both control and treated type IIB fibres, and an increase of CAF in ageing SKM upon RES-treatment. The present work suggests that capillarization is one of the determinants of the development of TAs and fatigue resistance, and that RES can be con- sidered a good candidate to counteract capillary rarefaction in the SKM tissue. more...

KEY POINTS Few days of unloading are sufficient to induce a decline of skeletal muscle mass and function; notably, contractile force is lost at a faster rate than muscle mass. The reasons behind this disproportionate loss of muscle force are still poorly understood. We provide strong evidence of two mechanisms only hypothesized until now for the rapid muscle force loss in only 10 days of bed rest. Our results show that an initial neuromuscular junction instability, accompanied by alterations in the innervation status and impairment of single fibre sarcoplasmic reticulum function contribute to the loss of contractile force in front of a preserved myofibrillar function and central activation capacity. Early onset of neuromuscular junction instability and impairment in calcium dynamics involved in excitation-contraction coupling are proposed as eligible determinants to the greater decline in muscle force than in muscle size during unloading. ABSTRACT Unloading induces rapid skeletal muscle atrophy and functional decline. Importantly, force is lost at a much higher rate than muscle mass. We aimed to investigate the early determinants of the disproportionate loss of force compared to that of muscle mass in response to unloading. Ten young participants underwent 10 days of bed rest (BR). At baseline (BR0) and at 10 days (BR10), quadriceps femoris (QF) volume (VOL) and isometric maximum voluntary contraction (MVC) were assessed. At BR0 and BR10 blood samples and biopsies of vastus lateralis (VL) muscle were collected. Neuromuscular junction (NMJ) stability and myofibre innervation status were assessed, together with single fibre mechanical properties and sarcoplasmic reticulum (SR) calcium handling. From BR0 to BR10, QFVOL and MVC decreased by 5.2% (P = 0.003) and 14.3% (P more...

Background Recently many serological assays for detection of antibodies to SARS-COV-2 virus were introduced on the market. Aim of this study was to assess the diagnostic performance of an automated CLIA for quantitative detection of anti-SARS-CoV-2 IgM and IgG antibodies. Methods A total of 354 sera, 89 from consecutive patients diagnosed with COVID-19 (43 mild, 32 severe and 13 critical) and 265 from asymptomatic and negative on rRT-PCR testing healthcare workers, were evaluated for IgM and IgG anti-SARS-CoV-2 antibodies with MAGLUMI immunoassay. Results The overall sensitivity and specificity were 86.5% (95%CI: 77.6–92.8) and 98.5% (95%CI:96.2–99.6), respectively. PPV, PPN, LR+, LR- and OR were 95.1 (95%CI: 87.8–98.6), 95.6 (95%CI: 92.4–97.7), 57.3 (95%CI: 21.6–152.1), 7.3 (95%CI: 4.31–12.4) and 418.6 (95%CI: 131.2–1335.2), respectively. The levels of SARS-CoV-2 IgM and IgG antibodies were 1.22 ​± ​1.2 AU/mL and 15.86 ​± ​24.83 AU/mL, 2.86 ​± ​2.4 AU/mL and 69.3 ​± ​55.5 AU/mL, 2.47 ​± ​1.33 AU/mL and 83.9 ​± ​83.9 AU/mL in mild, severe and critical COVID-19 groups, respectively. A significant difference in antibody levels between mild and severe/critical subjects has been shown. Conclusions The CLIA assay showed good diagnostic performance and a significant association between antibody levels and severity of the disease was found. more...

Essentials Between-lab variations of cut-off values in lupus anticoagulant detection are unknown. Cut-off values were calculated in 11 labs each testing plasma from 120 donors with 3 platforms. Major variation was observed even within the same platform. Cut-off values determined in different labs are not interchangeable. SummaryBackground Cut-off values for interpretation of lupus anticoagulant (LA) detection are poorly investigated. Aims (i) To assess whether results from healthy donors were normally distributed and (ii) the between-laboratories differences in cut-off values for screening, mixing and LA confirmation when calculated as 99th or 95th centiles, and (iii) to assess their impact on the detection rate for LA. Methods Each of 11 laboratories using one of the three widely used commercial platforms for LA detection was asked to collect plasmas from 120 healthy donors and to perform screening, mixing and LA confirmation with two methods (activated partial thromboplastin time [APTT] and dilute Russell viper venom [dRVV]). A common set of LA-positive or LA-negative freeze-dried plasmas was used to assess the LA detection rate. Results were centralized (Milano) for statistical analysis. Results and conclusions (i) Clotting times or ratios for healthy subjects were not normally distributed in the majority of cases. The take-home message is that cut-off values should be determined preferably by the non-parametric method based on centiles. (ii) There were relatively large inter-laboratory cut-off variations even within the same platform and the variability was marginally attenuated when results were expressed as ratios (test-to-normal pooled plasma). The take-home message is that cut-off values should be determined locally. (iii) There were differences between cut-off values calculated as 99th or 95th centiles that translate into a different LA detection rate (the lower the centile the greater the detection rate). The take-home message is that cut-off values determined as the 95th centile allow a better LA detection rate. more...

Muscle fatigue is defined as any decline in muscle performance associated with its activity. Fatigue is triggered by several factors as Ca2 + metabolism, blood flow, oxygen supply, and metabolic-energetic alterations that are strictly correlated with prooxidant/antioxidant equilibrium of the cell. During aging the skeletal muscle undergoes an important mass reduction, alteration of oxidative defense, mitochondrial function, sensitivity to insulin, and inflammatory response, accompanied by the gradual decline in its functions, resulting in the complex syndrome named sarcopenia. Resveratrol is a small polyphenol found in grapevine skin, peanuts, and in some berries known for its antioxidant properties and recently suggested as a potential agent to combat sarcopenia. Resveratrol displays several properties that have been suggested as responsible of the amelioration of the age-related muscular functional decline. Here, we report data and suggested mechanisms on resveratrol capability to modulate the decline of the resistance to fatigue in the aging muscle. more...

QuantiFERON -TB Gold plus (QFT-plus) represents the latest generation of interferon-gamma release assays (IGRAs), eliciting a response from CD8 T- cells in addition to CD4-T cells, with the aim to improve detection of latent M.tuberculosis infection (LTBI) with respect to its predecessor QuantiFERON-TB Gold In-Tube (QFT-GIT), even if no significant differences have been shown between the two tests (1, 2).…. more...

Sporadic small vessel disease (SVD) has high prevalence in aging population and stroke patients, but also in younger asymptomatic subjects. In this last group it can represents a prelude to stroke and cognitive impairment. Still nowadays, its pathogenesis is unclear. 35 consecutive patients with SVD at brain MRI and 35 age- and sex-matched controls, between January 2016 and February 2018, underwent an extended screening for thrombophilia, autoimmunity and evaluated levels of blood markers of inflammation and endothelial activation. Asymmetric DiMethyl Arginine (ADMA) levels proved higher in patients (70.44 ± 36.25 ng/ml vs. 46.58 ± 30.67 ng/ml; p = 0.004), also after controlling for confounding factors. ADMA levels showed positive correlation with Fazekas score (r = 0.304; p = 0.01). ROC curve analysis showed a moderate accuracy in discriminating patients and controls (AUC = 0.70; CI 0.57–0.82; p = 0.004): a cut-off of 46 ng/ml is associated with 80% sensitivity, but limited (54%) specificity. Higher ADMA levels characterize selected subjects with sporadic SVD, asymptomatic for vascular diseases and without latent inflammatory conditions or coagulopathy. This reinforces the hypothesis of the key role of endothelial dysfunction in SVD. Further studies should explore the cause-effect relationship between ADMA pathway and SVD. more...

Background Hemostasis is the dynamic equilibrium between coagulation and fibrinolysis. During pregnancy, the balance shifts toward a hypercoagulative state; however placental abruption and abnormal placentations may lead to rapidly evolving coagulopathy characterized by the increased activation of procoagulant pathways. These processes can result in hypofibrinogenemia, with fibrinogen levels dropping to 2 g/L or less and an associated increased risk of post-partum hemorrhage. The aim of the present study was to evaluate the concordance between two methods of functional fibrinogen measurement: the Thromboelastography (TEG) method (also known as FLEV) vs. the Clauss method. Three patient groups were considered: healthy volunteers; non-pathological pregnant patients; and pregnant patients who went on to develop postpartum hemorrhage. Methods A prospective observational study. Inclusion criteria were: healthy volunteer women of childbearing age, non-pathological pregnant women at term, and pregnant hemorrhagic patients subjected to elective or urgent caesarean section (CS), with blood loss exceeding 1000 mL. Exclusion criteria were age more...

SUMMARYThe prompt availability of reliable epidemiological information on emerging pandemics is crucial for public health policy-makers. Early in 2013, a possible new H1N1 epidemic notified by an intensive care unit (ICU) to GiViTI, the Italian ICU network, prompted the re-activation of the real-time monitoring system developed during the 2009–2010 pandemic. Based on data from 216 ICUs, we were able to detect and monitor an outbreak of severe H1N1 infection, and to compare the situation with previous years. The timely and correct assessment of the severity of an epidemic can be obtained by investigating ICU admissions, especially when historical comparisons can be made. more...

Resveratrol (RES) is a polyphenolic compound found in grapes, peanuts, and in some berries. RES has been reported to exhibit antioxidant, anti-inflammatory, anti-proliferative properties, and to target mitochondrial-related pathways in mammalian cells and animal models. Therefore, RES is currently advised as supplement in the diet of elderly individuals. Although it is hypothesized that some of RES beneficial actions likely arise from its action on the skeletal muscle, the investigation of RES effects on this tissue remains still elusive. This study reports the effects of a 0,04% RES-supplemented diet for six months, on the skeletal muscle properties of C57/BL6 aging mice. The analysis of the morphology, protein expression, and functional-mechanical properties of selected skeletal muscles in treated compared to control mice, revealed that treated animals presented less tubular aggregates and a better resistance to fatigue in an ex-vivo contraction test, suggesting RES as a good candidate to reduce age-related alterations in muscle. more...

The aim of this study is to investigate thrombogenesis and the hypercoagulable changes in pregnant women affected by thrombophilia who received low-molecular-weight heparin (LWMH) prophylaxis. We included 21 pregnant women affected by thrombophilia treated with LWMH and 20 nontreated normal pregnant women as the control group. The sample group of thrombophilic pregnant women included different conditions (factor V Leiden mutation, protein C deficiency, protein S deficiency, antiphospholipid antibodies syndrome, and combined defects). Three blood samples were collected during pregnancy (i.e., at 16, 20, and 24 weeks) and tested for activated partial thromboplastin time and prothrombin fragment F1 + 2 (F1 + 2); anti-FXa activity was tested only in treated thrombophilic pregnant women. F1 + 2 levels progressively increased during pregnancy in both study groups. However, the F1 + 2 increase in women exposed to heparin prophylaxis was significantly lower than that in normal pregnant women in all 3 measurements carried out during gestation (p < 0.05); a statistically significant inverse correlation between F1 + 2 levels and anti-Xa activity (R = -0.8575, p < 0.05) was observed in treated women during pregnancy. Our findings suggest that F1 + 2 in addition to anti-Xa measurement could be used to adjust LWMH prophylaxis, at least in high-risk pregnant women. more...

Summary When pluripotency factors are removed, embryonic stem cells (ESCs) undergo spontaneous differentiation, which, among other lineages, also gives rise to cardiac sublineages, including chamber cardiomyocytes and pacemaker cells. Such heterogeneity complicates the use of ESC-derived heart cells in therapeutic and diagnostic applications. We sought to direct ESCs to differentiate specifically into cardiac pacemaker cells by overexpressing a transcription factor critical for embryonic patterning of the native cardiac pacemaker (the sinoatrial node). Overexpression of SHOX2 during ESC differentiation upregulated the pacemaker gene program, resulting in enhanced automaticity in vitro and induced biological pacing upon transplantation in vivo. The accentuated automaticity is accompanied by temporally evolving changes in the effectors and regulators of Wnt signaling. Our findings provide a strategy for enriching the cardiac pacemaker cell population from ESCs., Highlights • SHOX2 accentuates the molecular profile of pacemaker cells in differentiating ESCs • SHOX2 increases the frequency and rate of spontaneously active cardiac derivatives • SHOX2-overexpressing EBs function as biopacemakers when transplanted in vivo • Wnt signaling underlies SHOX2-mediated pacemaker cell specification, Cho and colleagues show that heterologous SHOX2 expression boosts the differentiation of embryonic stem cells to cardiac pacemaker cells from embryonic stem cells by enhancing pacemaker cell-specific electrophysiology. Implantation of SHOX2-overxpressing embryoid bodies to the rat heart in vivo creates biological pacing. The SHOX2-facilitated pacemaker cell phenotype correlates with specific Wnt modulation, suggesting that Wnt may be a negotiator for cardiac subtype specification. more...

Quality of life (QoL) is the sense of well-being perceived by people. The improvement of parkinsonian patient’s QoL is a crucial goal for clinicians involved in rehabilitative care. In order to provide an appropriate endpoint for the assessment of the effectiveness of rehabilitation treatments on QoL of patients with Parkinson’s Disease (PD), in this study we have first translated and then validated the Belastungsfragebogen Parkinson kurzversion (BELA-P-k). This tool allows evaluating separately two crucial aspects: i) the loss of personal autonomy in activities of daily life and ii) the psychological and psychosocial impact of the disease. The BELA-P-k was translated from Dutch into Italian. Subsequently 202 PD patients filled out the questionnaire. Patients were also evaluated by using the Parkinson Disease Questionnaire −39 (PDQ39), the Unified Parkinson’s Disease Rating Scale (UPDRS), the Mini Mental State Examination (MMSE) and the Frontal Assessment Battery (FAB). The internal consistency for total of two different scores Bothered by (Bb) and Need for Help (NfH) was excellent (p = 0.91) for both categories. The correlation between Bb and NfH categories was significant and strong, very-strong, ranging from 0.78 to 0.88 (all p more...

Gastrointestinal stromal tumors (GIST) are rare, with unpredictable behavior, most of them asymptomatic or nonspecific symptoms. They may arise in any place of digestive tube, and the standard treatment is the complete surgical resection, however recurrences and metastases are frequent. The following case is a report from an elderly patient with growing and painful abdominal mass on physical examination, and the result of complementary imaging tests suggests that this is GIST. Submitted to surgical therapy for resection of the lesion and follow-up with imatinib mesylate (Glivec®). more...

The goal of a total knee replacement is a good Range of Motion, pain relief, stability. All these factors are mandatory to achieve a long time survive of the implant and a individual satisfaction. Ligament balancing is the main part to implant a total knee prothesis in a right way. There are 2 ways to have a ligament balanced prothesis; the bony landmark technique and the gap balancing technique. The 2 technique are evaluated but We thing that the best is to use a mixed technique. more...

This study describes the expression of the voltage operated calcium channels (VOCCs) subunits α1A (typical of the P/Q family) and α1D (of the L family) in the bovine hypothalamus. The expression of both P/Q and L families has been characterized in the brain of adult mammals. However, their distribution and expression during foetal neuronal differentiation have not yet been determined. The expression profile of the α1A and α1D pore-forming subunits was investigated during four embryonic stages in bovine foetuses. Our data suggest that the expressions of α1A and α1D are correlated during development, with an increase only in males that peaks on the last period of gestation. Bovine male hypothalami showed significantly higher α1A and α1D expression values in comparison to female ones during the whole developmental period. In the females, the expression profiles of both genes were constant during all the developmental time. Immunohistochemical studies confirmed the presence of the α1A and α1D protein subunits in foetal hypothalamic neurones starting from the third foetal stage. Our data provide new information on the hypothalamic expression of α1A and α1D subunits during development in a mammal with a long gestation period and a large and convoluted brain. more...

Purpose To explore the role of plasmatic platelet-activating factor acetylhydrolase (PAF-AH), a marker of cardiovascular risk, in patients with anti-phospholipid antibodies (aPL). Methods PAF-AH activity was assessed in a series of 167 unselected patients screened for aPL in a context of thrombotic events, risk of thrombosis or obstetric complications and in 77 blood donors. Results 116/167 patients showed positive results for at least one aPL among IgG/IgM anti-prothrombin/phosphatidylserine (aPS/PT), anti-cardiolipin (aCL), anti-beta2-glycoprotein I (aβ2GPI) or lupus anticoagulant (LAC), while 51/167 patients resulted aPL-negative. LAC+ patients disclosed higher PAF-AH than LAC-negative (22.1 ± 6.4 nmol/min/ml vs. 19.5 ± 4.1 nmol/min/ml; p = 0.0032), and aPL-negative patients (p = 0.03). Patients presenting positive IgG aβ2GPI disclosed higher PAF-AH than patients with only IgM aβ2GPI-positive antibodies (23.1 ± 7.2 nmol/min/ml vs. 20.1 ± 5.3 nmol/min/ml; p = 0.035), as well as than patients showing only isolated LAC, aCL or aPS/PT (16.9 ± 3.8 nmol/min/ml; p = 0.003). Conclusions PAF-AH plasmatic activity is particularly up-regulated in LAC+ and in aβ2GPI IgG+ patients, possibly representing an alternative prognostic biomarker for the therapeutic management of APS patients. more...

BACKGROUND The number of elderly patients undergoing major surgical interventions and then needing admission to intensive care unit (ICU) grows steadily. We investigated this issue in a cohort of 232,278 patients admitted in five years (2011-2015) to 163 Italian general ICUs. METHODS Surgical patients older than 75 registered in the GiViTI MargheritaPROSAFE project were analyzed. The impact on hospital mortality of important chronic conditions (severe COPD, NYHA class IV, dementia, end-stage renal disease, cirrhosis with portal hypertension) was investigated with two prognostic models developed yearly on patients staying in the ICU less or more than 24 hours. RESULTS 44,551 elderly patients (19.2%) underwent emergency (47.3%) or elective surgery (52.7%). At least one severe comorbidity was present in 14.6% of them, yielding a higher hospital mortality (32.4%, vs. 21.1% without severe comorbidity). In the models for patients staying in the ICU 24 hours or more, cirrhosis, NYHA class IV, and severe COPD were constant independent predictors of death (adjusted odds ratios [ORs] range 1.67-1.97, 1.54-1.91, and 1.34-1.50, respectively), while dementia was statistically significant in four out of five models (adjusted ORs 1.23-1.28). End-stage renal disease, instead, never resulted to be an independent prognostic factor. For patients staying in the ICU less than 24 hours, chronic comorbidities were only occasionally independent predictors of death. CONCLUSIONS Our study confirms that elderly surgical patients represent a relevant part of all ICUs admissions. About one of seven bear at least one severe chronic comorbidity, that, excluding end-stage renal disease, are all strong independent predictors of hospital death. more...

The enzyme aromatase (P450(AROM)) converts testosterone (T) into 17-β estradiol (E(2)) and is crucial for the control of development of the central nervous system during ontogenesis. The effects of E(2) in various brain areas are mediated by the estrogen receptor alpha (ER-α) and the estrogen receptor beta (ER-β). During fetal development, steroids are responsible for the sexual differentiation of the hypothalamus. Estrogens are also able to exert effects in other brain areas of the fetus including the frontal cortex, where they act through estrogen receptors (ERs) modulating cognitive function and affective behaviors. In this study we have determined the expression profiles of P450(AROM) and ERs in the fetal bovine frontal cortex by quantitative Real-Time PCR (qRT-PCR) throughout the prenatal development. The data show that the patterns of expression of both ERs are strongly correlated during pregnancy and increase in the last stage of gestation. On the contrary, the expression of P450(AROM) has no correlation with ERs expression and is not developmentally regulated. Moreover, we performed immunochemical studies showing that fetal neurons express P450(AROM) and the ERs. P450(AROM) is localized in the cytoplasm and only seldom present in the fine extensions of the cells; ER-α is detected predominantly in the soma whereas ER-β is only present in the nucleus of a few cells. This study provides new data on the development of the frontal cortex in a long gestation mammal with a large convoluted brain. more...

Heart failure remains one of the main causes of morbidity and mortality in the Western world. Current therapies for myocardial infarction are mostly aimed at blocking the progression of the disease, preventing detrimental cardiac remodeling and potentiating the function of the surviving tissue. In the last decade, great interest has arisen from the possibility to regenerate lost tissue by using cells as a therapeutic tool. Different cell types have been tested in animal models, including bone marrow-derived cells, myoblasts, endogenous cardiac stem cells, embryonic cells and induced pluripotent stem cells. After the conflicting and often inconsistent results of the first clinical trials, a step backward needs to be performed, to understand the basic biological mechanisms underlying spontaneous and induced cardiac regeneration. Current studies aim at finding new strategies to enhance cellular homing, survival and differentiation in order to improve the overall outcome of cellular cardiomyoplasty. more...

The management of Incarcerated Inguinal Hernia (IIH) in children is challenging and may be associated with complications. We aimed to compare the outcomes of laparoscopic vs. open repair of IIH.With institutional ethical approval (09SG13), we reviewed the notes of 63 consecutive children who were admitted to a single hospital with the diagnosis of IIH between 2000 and 2008. Data are reported as median (range). Groups were compared by chi-squared or t-tests as appropriate.· Open repair (n=35): There were 21 children with right and 14 with left IIH. 2 patients also had contralateral reducible inguinal hernia. Small bowel resection was required in 2 children. · Laparoscopic repair (n=28): All children had unilateral IIH (19 right sided, 9 left sided). 15 children (54%) with no clinical evidence of contralateral hernia, had contralateral patent processus vaginalis at laparoscopy, which was also repaired. The groups were similar with regard to gender, age at surgery, history of prematurity, interval between admission and surgery, and proportion of patients with successful preoperative manual reduction. However, the duration of operation was longer in the laparoscopy group (p=0.01). Time to full feeds and length of hospital stay were similar in both groups. Postoperative follow-up was 3.5 months (1-36), which was similar in both groups. 5 patients in the group undergoing open repair had serious complications: 1 vas transaction, 1 acquired undescended testis, 2 testicular atrophy and 1 recurrence. The laparoscopic group had a single recurrence.Open repair of incarcerated inguinal hernia is associated with serious complications. The laparoscopic technique appears safe, avoids the difficult dissection of an oedematous sac in the groin, allows inspection of the reduced hernia content and permits the repair of a contralateral patent processus vaginalis if present. more...

Introduction Thoracoscopic repair of congenital diaphragmatic hernia (CDH) has been described, but its efficacy and safety have not been validated. The aim was to compare our experience of thoracoscopy with laparotomy repair. Methods After ethics approval, we reviewed the notes of neonates with CDH operated in our institution between 2003 and 2008. Two historical groups were compared: infants who underwent laparotomy (2003-2008) or thoracoscopy (2007-2008). Data were compared by t test or Mann-Whitney tests. Results Thirty-five children had open repair of CDH, and 13 had thoracoscopic repair. Groups were homogeneous for age and weight. Five (38%) neonates who had thoracoscopy were converted to open for surgical difficulties (n = 4) and O 2 desaturation (n = 1). Patch repair was used in 12 (34%) open and 6 (46%) thoracoscopic repairs. End-tidal CO 2 was significantly elevated during thoracoscopy, but this was not reflected in arterial CO 2 or pH. There were 3 (8%) recurrences after open repair and 2 (25%) after thoracoscopy ( P = .19). Conclusion Thoracoscopic repair of CDH is feasible. Arterial blood gases should be closely monitored. Despite higher EtCO 2 , conversion to open was mainly because of difficult repair. A randomized trial is necessary to assess the effect of thoracoscopy on ventilation and recurrences. more...

Arterial hypertension has a high prevalence in population in general and is an important risk factor for the development of cardiovascular diseases. Changes in the lifestyle such as a regular practice of physical exercises not only contributes for the reduction of blood pressure, but also bring some additional benefits for the whole body. Th erefore, the objective of this study was to evaluate the changes in the blood pressure and the cardiorespiratory capacity in individuals in an aerobic physical training program. This study included nine healthy sedentary men (48.44 ± 6.26 years old), who participated in an aerobic physical training three times a week for 12 weeks with an intensity of 70 to 85% of the maximal heart rate obtained in the treadmill test until exhaustion. Height, total body mass, heart rate and the blood pressure (both at rest) oxygen consumption and peak power were measured. The results obtained show signifi cant changes: a decrease of the total body mass in the body mass index, in the heart rate, and in the systolic blood pressure at rest, and an increase in the peak power. The aerobic physical training used was effective for the studied population, contributing significantly for the change and control of the components evaluated in a short period of training intervention. more...

To estimate the prevalence of violence, depressive symptoms, and associated factors during pregnancy in women attending antenatal care in Brazil. Violence was assessed using a modified version of the abuse assessment screen (ASS), and depressive symptoms were evaluated using the primary care evaluation of mental disorders (PRIME-MD). Participants were pregnant women attending 18 primary care units in Rio Grande do Sul, Brazil, between June 2006 and April 2007. A total of 712 pregnant women participated, but only 627 of them responded the ASS. Experience of any lifetime violence was reported by 273 (43.4%) women and 114 (18.2%) reported violence during the current pregnancy. One-third of them (n = 211) reported lifetime domestic violence and 100 (15.9%) women reported this type of violence during the current pregnancy. Experience of domestic violence during pregnancy was more common in unemployed women, among those with two or more children, with a higher consumption of alcohol, and who had not planned their current pregnancy. Of the total of sample (n = 712), 198 (27.8%) women reported six or more depressive symptoms. The presence of depressive symptoms during pregnancy was associated with low educational levels, living in a household with five or more people, and with higher consumption of alcohol during pregnancy. Pregnant women attending primary care are exposed to high rates of domestic violence, and many have clinically relevant depressive symptoms. Appropriate interventions to avoid or minimize the effects of violence and mental disorders to the well-being of the mothers and their babies are urgently required. Primary care services play an important role in identifying and supporting women at risk. more...

The grass goby Zosterisessor ophiocephalus sperm-duct gland extract displayed antimicrobial activity against gram-positive and gram-negative bacteria. This suggests that sperm-duct gland mucins might be functional in protecting eggs and possibly parents from pathogens, an activity of great adaptive value for Z. ophiocephalus, which lays eggs in mud nests. more...

The physiological properties and role of the type 3 ryanodine receptor (RyR3), a calcium release channel expressed in a wide variety of cell types, remain mysterious. We forced, in vivo, the expression of RyR3 in adult mouse skeletal muscle fibres using a GFP-RyR3 DNA construct. GFP fluorescence was found within spatially restricted regions of muscle fibres where it exhibited a sarcomere-related banded pattern consistent with a localization within or near the junctional sarcoplasmic reticulum membrane. Immunostaining confirmed the presence of RyR3 together with RyR1 within the GFP-positive areas. In ∼90% of RyR3-positive fibres microinjected with the calcium indicator fluo-3, we detected repetitive spontaneous transient elevations of intracellular Ca2+ that persisted when fibres were voltage-clamped at −80 mV. These Ca2+ transients remained essentially confined to the RyR3 expression region. They ranged from wide local events to propagating Ca2+ waves and were in some cases associated with local contractile activity. When voltage-clamp depolarizations were applied while fluo-3 or rhod-2 fluorescence was measured within the RyR3-expressing region, no voltage-evoked ‘spark-like’ elementary Ca2+ release event could be detected. Still global voltage-activated Ca2+ release exhibited a prominent early peak within the RyR3-expressing regions. Measurements were also taken from muscles fibres expressing a GFP-RyR1 construct; positive fibres also yielded a local banded pattern of GFP fluorescence but exhibited no spontaneous Ca2+ release. Results demonstrate that RyR3 is a very potent source of voltage-independent Ca2+ release activity. Conversely we find no evidence that it could contribute to the production of discrete voltage-activated Ca2+ release events in differentiated mammalian skeletal muscle. more...

SummaryUnderstanding of developmental haemostasis is critical to ensure optimal prevention, diagnosis, and treatment of haemorrhagic and thrombotic diseases in children. As coagulation test results are known to be dependent on the reagents/analysers used, it is recommended for each laboratory to define the age-dependent reference ranges by using its own technical condition. That study was carried out in seven centers to establish age-specific reference ranges using the same reagents and analyser. Plasma samples were obtained from 1437 paediatric patients from the following age groups: 15 days-4 weeks (n=36), 1–5 months (n=320), 6–12 months (n=176), 1–5 years (n=507), 6–10 years (n=132) and 11–17 years (n=262). Indication of coagulation testing was pre-operative screening for non-acute diseases in most cases. PT values were similar in the different age groups to those in adults, whereas longer aPTTs were demonstrated in the younger children. Plasma levels of all clotting factors, except for FV, were significantly decreased (p more...

Laboratory assessment of Lupus anticoagulant (LAC) is very challenging because of inter and intralaboratory variability, which makes it difficult to standardize and harmonize results expression. Five hospital laboratories in North-eastern Italy shared their efforts and their experience in a cross-laboratory study, conducting the diagnostic process as homogeneously as possible and providing a better interpretation for LAC positivity. Hundred normal samples from healthy subjects (20 from each center) were processed to confirm negative upper limits and calculate positivity cutoffs of LAC integrated assays, that is dilute Russell's viper venom time (dRVVT) and silica clotting time (SCT). Moreover, 311 samples previously diagnosed by the laboratories as positive for LAC were analyzed to characterize different positivity levels for each assay. As far as the analysis of healthy subjects is concerned, negative upper limits are set at 1.17 and 1.19 for dRVVT and SCT screen ratio, respectively. Positivity cutoffs are set at 1.20 for dRVVT and 1.23 for SCT, expressed as Test Ratio calculated on screen and confirm integrated tests. Positive results for each integrated assay are subsequently divided into three subgroups: weak, moderate and strong; the results obtained are presented as a score proposal that can provide LAC interpretation. The combined use of both dRVVT and SCT assays and the definition of different positivity levels may lead to clearer, more objective LAC reporting. An interpretative table for LAC-proposed score provides LAC-positive results and it is now adopted by all centers involved in the study. more...

Torsion of a wandering spleen is a rare cause of acute abdomen in children, usually diagnosed with color-Doppler ultrasonography and enhanced computed tomography. We report a pediatric case of torsion of wandering spleen. more...

There is disagreement as to whether it is safe to place implants in patients under bisphosphonates (BPs) therapy owing to the risk for developing BP-related osteonecrosis of the jaws (BRONJ). The American Association of Oral and Maxillofacial Surgeons recommends that dental implants should be avoided in oncologic patients treated with intravenous BPs. Conversely, for patients receiving oral BPs, dental implant placement is not explicitly contraindicated even if a cautious approach is suggested. The aim of the current study was to assess the risk level as related to adverse events such as implant failure and BRONJ in a large cohort of osteoporotic patients submitted to implant placement and concomitant application of plasma rich in growth factor (PGRF)-Endoret. The clinical charts of 235 middle-aged women under oral BPs therapy for osteoporosis, who underwent positioning of 1267 dental implants, were reviewed. The implants were always positioned in association with PRGF-Endoret. The outcomes were implant failure and BRONJ. A model based on personal risk factors distribution was used for risk assessment. Sixteen implants were lost in 16 patients up to 120 months of follow-up, leading to a survival of 98.7% and 93.2% on an implant basis and patient basis, respectively. No cases of BRONJ were reported. In line with the current literature, the present data show that the risk for developing BRONJ associated to dental implant surgery remains low for patients receiving oral BPs. The use of procedures that could enhance and support healing, such as platelet concentrates, should be recommended. more...

Presenilin-1 and -2 (PS1 and PS2) mutations, the major cause of familial Alzheimer's disease (FAD), have been causally implicated in the pathogenesis of neuronal cell death through a perturbation of cellular Ca(2+) homeostasis. We have recently shown that, at variance with previous suggestions obtained in cells expressing other FAD-linked PS mutations, PS2-M239I and PS2-T122R cause a reduction and not an increase in cytosolic Ca(2+) rises induced by Ca(2+) release from stores. In this contribution we have used different cell models: human fibroblasts from controls and FAD patients, cell lines (SH-SY5Y, HeLa, HEK293, MEFs) and rat primary neurons expressing a number of PS mutations, e.g. P117L, M146L, L286V, and A246E in PS1 and M239I, T122R, and N141I in PS2. The effects of FAD-linked PS mutations on cytosolic Ca(2+) changes have been monitored either by using fura-2 or recombinant cytosolic aequorin as the probe. Independently of the cell model or the employed probe, the cytosolic Ca(2+) increases, caused by agonist stimulation or full store depletion by drug treatment, were reduced or unchanged in cells expressing the PS mutations. Using aequorins, targeted to the endoplasmic reticulum or the Golgi apparatus, we here show that FAD-linked PS mutants lower the Ca(2+) content of intracellular stores. The phenomenon was most prominent in cells expressing PS2 mutants, and was observed also in cells expressing the non-pathogenic, "loss-of-function" PS2-D366A mutation. Taken as a whole, our findings, while confirming the capability of presenilins to modify Ca(2+) homeostasis, suggest a re-evaluation of the "Ca(2+) overload" hypothesis in AD and a new working hypothesis is presented. more...

Aim of this study is analyze the effects of dental occlusion on postural stability in patients with previous whiplash and malocclusion. Materials and methods: 30 adult patients with previous whiplash and malocclusion (crossbite, mandibular shift, bad alignment, edentulous spaces) were selected. The patients were suffering from masticatory muscles pain caused by clenching during sleep. Exclusion criteria: use of psych drugs. To simulate the conditions of sleep (with a reduction of proprio- and esteroceptive inputs for postural management performed by CNS), we used postural Romberg analysis (feet together, closed eyes) on stabilometric platform changing occlusal parameters only, under the following conditions: 1) in occlusal rest position, 2) in centric occlusion, 3) in clenching, 4) with occlusal disengage with cotton rolls and 5) in clenching on cotton rolls. Time of each test: 15 seconds. It was performed a statistical analysis with T-test comparing between them the mean of all tests. Results: stabilometry data (postural ball and ellipse) show better postural with occlusal disengage (in centric and in clenching), and a worsening in all tests with centric occlusion (with statistically significant difference - p more...

There are many types of cancers in children that are very different from those found in adults: leukaemia, lymphoma, and brain tumours are rather common in children. Acute lymphoblastic leukaemia (ALL) is the most common type of malignancy encountered. The role of pediatric dentist is very important before, during and after therapy: up to 24% of life-threatening infections arise from oral sites and areas. Early dental intervention and preventions procedures may significantly reduce oral complications associated with myelosuppressive cancer treatment. It is really important to evaluate the oral health surveys and to cut out potential sources of infection in mouth in these patients concurrent with their medical therapy. The aim of this review is summarizing the main features of oral mucositis in Childhood Acute Lymphoblastic Leukaemia, providing a little review for the approach, diagnosis and treatment of oral mucositis of ALL, which is frequent and potentially dangerous: it's important considering oral lesions of this type of childhood cancer in order to prevent complications before, during and after chemo or radio therapy to improve the quality of life of little patients. more...

Background: Idiopathic varicocele is one of the causes of potentially correctable male subfertility. The mechanisms causing spermatogenesis impairment have yet to be clarified. The aim of this study is to analyze the effects of renal and adrenal metabolite reflux on testicular exocrine function in a rat experimental model. Materials and Methods: In the study, 45 male Lewis Stock adult rats, each weighing 300 g, were used. The rats were subdivided into three groups of 15 rats. In group A (control group) testicular volume and basal follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were measured at the beginning of the study and after 9 months. In group B, varicocele was induced by means of rings introduced in the left renal vein in order to cause a renospermatic reflux. In group C, similarly to group B, varicocele was induced after removal of left adrenal gland. The effects of varicocele on testicular function were then analyzed 3, 6 and 9 months after surgery. After 9 months, all rats underwent testicular biopsy. Results: Both groups B and C showed a reduction in testicular volume, an increase in FSH and a decrease in testosterone levels. These levels were higher in group B. Testicular histological assessment showed important structural abnormalities in group B rats. Conclusions: These data support the hypothesis that renal and adrenal metabolites enhance varicocele-induced testicular damage. This theory is supported both by hormonal impairment and testicular histological analysis. more...

Experimental data suggest that cell-based therapies may be useful for cardiac regeneration following ischaemic heart disease. Bone marrow (BM) cells have been reported to contribute to tissue repair after myocardial infarction (MI) by a variety of humoural and cellular mechanisms. However, there is no direct evidence, so far, that BM cells can generate cardiac stem cells (CSCs). To investigate whether BM cells contribute to repopulate the Kit+ CSCs pool, we transplanted BM cells from transgenic mice, expressing green fluorescent protein under the control of Kit regulatory elements, into wild-type irradiated recipients. Following haematological reconstitution and MI, CSCs were cultured from cardiac explants to generate ‘cardiospheres’, a microtissue normally originating in vitro from CSCs. These were all green fluorescent (i.e. BM derived) and contained cells capable of initiating differentiation into cells expressing the cardiac marker Nkx2.5. These findings indicate that, at least in conditions of local acute cardiac damage, BM cells can home into the heart and give rise to cells that share properties of resident Kit+ CSCs. more...

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in childhood (Horm Res 70:65-72, 2008; J Clin Endocr Metab 93:869-875, 2008). 18−Fluoro-L-dihydroxy-phenylalanine (18F-DOPA) positron emission tomography (PET) can detect areas of increased activity in the pancreas and may differentiate focal from diffuse CHI (J Clin Endocr Metab 93:869-875, 2008; Radiology 253:216-222, 2009). We here report the case of a girl who complained of recurrent episodes of severe hypoglycaemia despite previous partial pancreatectomy. To evaluate the need for additional surgical intervention, we performed 18F-DOPA PET/computed tomography (CT), which showed a focal lesion corresponding to the anatomical region of the pancreatic tail. On the other hand, abdominal magnetic resonance imaging (MRI) clearly demonstrated that the 18F-DOPA uptake was in a loop of bowel occupying the previous surgical bed. Our case highlights that bowel uptake can be a possible pitfall in the interpretation of 18F-DOPA PET/CT in children affected by CHI, suggesting that when 18F-DOPA PET/CT results do not fit the clinical picture, magnetic resonance imaging (MRI) may allow a more accurate correlation of the radiotracer activity with the underlying anatomical or pathological structure. more...

Cardiac cell therapy suffers from limitations related to poor engraftment and significant cell death after transplantation. In this regard, ex vivo tissue engineering is a tool that has been demonstrated to increase cell retention and survival. The aim of our study was to evaluate the therapeutic potential of a 3D-printed patch composed of human cardiac-derived progenitor cells (hCMPCs) in a hyaluronic acid/gelatin (HA/gel) based matrix. hCMPCs were printed in the HA/gel matrix (30 x 10(6) cells/ml) to form a biocomplex made of six perpendicularly printed layers with a surface of 2 x 2 cm and thickness of 400 um, in which they retained their viability, proliferation and differentiation capability. The printed biocomplex was transplanted in a mouse model of myocardial infarction (MI). The application of the patch led to a significant reduction in adverse remodeling and preservation of cardiac performance as was shown by both MRI and histology. Furthermore, the matrix supported the long-term in vivo survival and engraftment of hCMPCs, which exhibited a temporal increase in cardiac and vascular differentiation markers over the course of the 4 week follow-up period. Overall, we developed an effective and translational approach to enhance hCMPC delivery and action in the heart. (C) 2015 Elsevier Ltd. All rights reserved. more...

Diaphragmatic hernia in pediatric emergency department poses a diagnostic challenge because of the acute or subtle timing of onset and the wide variety of clinical features. We describe 3 different late presentations of Bochdalek diaphragmatic hernia in a pediatric emergency department. These reports may help physicians avoid delayed diagnosis of late-presenting congenital diaphragmatic hernia, thereby reducing the risk of inappropriate treatments and life-threatening conditions in children. more...

The epithelial-to-mesenchymal transition (EMT) is an essential trans-differentiation process, which plays a critical role in embryonic development, wound healing, tissue regeneration, organ fibrosis, and cancer progression. It is the fundamental mechanism by which epithelial cells lose many of their characteristics while acquiring features typical of mesenchymal cells, such as migratory capacity and invasiveness. Depending on the contest, EMT is complemented and balanced by the reverse process, the mesenchymal-to-epithelial transition (MET). In the saving economy of the living organisms, the same (Ying-Yang) tool is integrated as a physiological strategy in embryonic development, as well as in the course of reparative or disease processes, prominently fibrosis, tumor invasion and metastasis. These mechanisms and their related signaling (e.g., TGF-β and BMPs) have been effectively studied in vitro by tissue-derived cell spheroids models. These three-dimensional (3D) cell culture systems, whose phenotype has been shown to be strongly dependent on TGF-β-regulated EMT/MET processes, present the advantage of recapitulating in vitro the hypoxic in vivo micro-environment of tissue stem cell niches and their formation. These spheroids, therefore, nicely reproduce the finely regulated Ying-Yang equilibrium, which, together with other mechanisms, can be determinant in cell fate decisions in many pathophysiological scenarios, such as differentiation, fibrosis, regeneration, and oncogenesis. In this review, current progress in the knowledge of signaling pathways affecting EMT/MET and stemness regulation will be outlined by comparing data obtained from cellular spheroids systems, as ex vivo niches of stem cells derived from normal and tumoral tissues. The mechanistic correspondence in vivo and the possible pharmacological perspective will be also explored, focusing especially on the TGF-β-related networks, as well as others, such as SNAI1, PTEN, and EGR1. This latter, in particular, for its ability to convey multiple types of stimuli into relevant changes of the cell transcriptional program, can be regarded as a heterogeneous "stress-sensor" for EMT-related inducers (growth factor, hypoxia, mechano-stress), and thus as a therapeutic target. more...

Temporary tracheal balloons have been shown to improve lung growth in fetuses with severe congenital diaphragmatic hernia. Fetoscopic Endoluminal Tracheal Occlusion (FETO) is performed at 26-28 weeks gestation, and then is removed in utero at 34 weeks gestation at highly specialized centers. In case of preterm labor at a hospital without a specialized team, a number of techniques have been used to remove the balloon, sometimes with death of the newborn. We have successfully performed an ultrasound-guided approach to puncture and remove the tracheal balloon in a premature infant in an emergency setting at birth. After that she was treated for congenital diaphragmatic hernia at our Newborn Intensive Care Unit. more...

AIM The aim of this study was to explore a birthweight prediction model using ultrasound determined tissue thickness (SCTT) parameters. METHODS We measured routine ultrasonographic biometric parameters and in addition, fetal SCTT in 201 healthy singleton pregnancies. Mid-arm fat and lean mass, mid-thigh fat and lean mass, subscapular fat mass and abdominal fat mass (AFM) were measured in order to calculate a birthweight prediction model. Ultrasound measurements were analyzed using an 'anovarepeated measures model'. The growth rate (beta-slope) of the selected parameters was computed and the correlation coefficient with the birthweight and the Kendall rank correlation tau, were calculated. RESULTS From the ultrasound determined SCTT parameters, only abdominal circumference (AC), AFM, and MTLM showed a statistically significant trend. The beta-slope of mid-thigh lean mass was excluded since it exhibited significant correlation with the beta-slope of AFM. The final regression model could be calculated as: birthweight (gr.) = intercept +alpha(1)(AFM beta-slope) + alpha(2)(AC beta-slope), where alpha(1), alpha(2) represent regression coefficients. CONCLUSIONS We provide a graphical birthweight prediction model for clinical practice using conventional and specific ultrasound measurements of fetal subcutaneous tissue thickness. This model is based upon an overall analysis of the ultrasound estimated body components. more...

Background: The cornerstone of acute stroke therapy is intravenous rt-PA, with the goal of rapid thrombolysis and restoration of blood flow. Unfortunately, less than half of patients treated have a favorable outcome. Since recanalization is closely correlated with the clinical response, endogenous resistance to rt-PA may inhibit thrombolysis and neurologic improvement. The primary objective of this research study was to evaluate whether an in vitro clot lysis assay and thrombolytic biomarkers could predict response to IV rt-PA in acute ischemic stroke patients Methods: Ischemic stroke patients who received IV rt-PA were recruited from two sites (Augusta, GA and Udine, Italy). Blood samples were collected prior to rt-PA administration and a favorable clinical response to rt-PA was specified as an NIHSS score of two or less at 24 hours. The time required for 50% platelet-poor clot lysis (C50%) was measured by an in vitro turbidimetric assay. The endogenous major fibrinolytic inhibitors (tissue plasminogen inhibitor, PAI-1; and α2-antiplasmin, α2-AP), D-dimer, fibrinogen and pro-thrombin time (PT), were assessed and correlated with clinical outcome. Results: We enrolled 54 rt-PA recipients (63±15 years; 72% male, and 85% white). The mean NIHSS was 11.2±5.1 at admission and 8.2±8.1 at 24 hours; 36% of patients had a favorable clinical response. There was a moderate reduction in C50% among patients with a favorable clinical outcome compared to those with an unfavorable outcome (669.5±46.3 vs. 704.7±91.6; p=0.075). There was no significant difference in PT (13.6±0.8 sec vs. 13.8±1.2 sec; p=0.444), PAI-1(28.2±34.1 pg/mL vs. 19.8±25.9 pg/mL; p=0.321), α2-AP (85.1±7.2 % vs. 88.8±10.1 %; p=0.153), D-dimer (269.5±232.2 ng/mL vs. 368.2±444.6 ng/mL; p=0.303) or fibrinogen (318.1±71.4 mg/dL vs. 343.0±173.1 mg/dL; p=0.465) levels between subjects with favorable and unfavorable response to rt-PA. Summary: Lack of response to IV rt-PA in stroke patients may reflect endogenous resistance to fibrinolysis reflected by prolonged clot lysis in vitro. The utility of clot lysis to predict rt-PA unresponsiveness should be tested in a larger clinical study. more...

Purpose To evaluate the impact of the introduction of the anti-phosphatidylserine/prothrombin autoantibodies (aPS/PT) in the laboratory diagnostic process of anti-phospholipid antibody syndrome (APS). Methods Four hundred and twenty-one patients (71.5 % females; 53 ± 15 years) presenting a medical prescription for aPS/PT antibodies were consecutively enrolled in the study from March 2013 to August 2013. During the same period, aPS/PT were additionally investigated in a selected series of 62 patients characterized by difficult lupus anticoagulant (LA) tests interpretation and in a retrospective series of 52 LA positive cases with available data about anti-prothrombin (aPT) antibodies. The aPS/PT antibodies, as well as the anti-cardiolipin (aCL), the anti-β2 glycoprotein I (aβ2GPI) and the aPT antibodies were analyzed by ELISA. LA was tested according to the recommended criteria, performing both the screen and the confirm steps. Results Overall, aPS/PT IgM positive (>30 U/ml) and/or IgG frankly positive (>40 U/ml) antibodies were found in 49/421 (11.6 %) cases. Among the LA positive patients, we found 56.1 % aPS/PT positive versus 31.7 % aCL and/or aβ2GPI positive cases, with limited (17.1 %) simultaneous positivity. The PS/PT complex resulted the newly recognized specificity in about 27 % of patients recruited from the subset with difficult LA test interpretation. Compared to aPT antibodies, the aPS/PT antibodies displayed a much higher sensitivity (55.8 versus 15.4 %) in LA positive patients. Conclusions The introduction of aPS/PT antibodies in the diagnostic process of APS is highly recommended, since they disclose a notable diagnostic performance and a high correlation with LA activity, such that they can be a viable alternative. more...

Trichobezoars are concretions formed by the accumulation of hair or fibers in the gastrointestinal tract, usually associated with underlying psychiatric disorders in females between 13 and 20 years old. Endoscopy, the gold standard for diagnosis, brings some additional advantages: sample taking, size reducing and, rarely, mass removal. This study shows that endoscopy can cause severe complications resulting in a surgical emergency. more...

Objective: To ascertain the diagnostic ability of a computerized fetal heart rate (FHR) analysis system in the identification of patients at risk of fetal distress in labor. Study design: Five-hundred and seventy-seven healthy term pregnancies were enrolled in a prospective, cross-sectional study and subdivided into two groups, with (n = 90) or without (n = 487) fetal distress in labor. Computerized FHR recordings were performed periodically and regression analysis was performed in a univariate and multivariate way to assess the ability of the last FHR recording in the prediction of subsequent fetal distress. Results: The two groups showed a significant difference in almost all of the FHR parameters studied. The multivariate analysis showed that only the FHR baseline and the percentage of small accelerations were independently and significantly related to the labor outcome. The combination of these two parameters reaches a sensitivity of 45%, specificity of 91%, positive predictive value of 48% and negative predictive value of 90%, with an overall accuracy of 84%. Conclusions: The increase in FHR baseline and in small FHR accelerations can be major factors in the prediction of subsequent fetal distress in healthy term fetuses. more...

It has been previously demonstrated that hyperglycaemia activates haemostasis; diabetes mellitus is considered a thrombosis-prone state. Acarbose, by inhibiting dietary carbohydrate absorption, reduces post-meal hyperglycaemia. In this study we evaluated the effect of post-meal hyperglycaemia on two markers of coagulation activation: prothrombin fragments 1 + 2 and D-dimer. Seventeen non-insulin-dependent diabetic patients maintained on diet therapy alone were randomly assigned to receive — with a cross-over study design — acarbose (100 mg orally) or placebo before a standard meal. Blood samples for measurement of plasma glucose, insulin, prothrombin fragments 1 + 2 and D-dimer were drawn at 0, 60, 120 and 240 min. After both placebo and acarbose, hyperglycaemia and hyperinsulinaemia which followed a standard meal were accompanied by a significant increase of plasma concentration of prothrombin fragments 1 + 2 and D-dimer in comparison to their baseline values. Acarbose administration significantly reduced the rise of glucose, insulin, prothrombin fragments 1 + 2 and D-dimer from 0 to 240 min in comparison to placebo. We conclude that post-meal hyperglycaemia, at the level reached by many diabetic patients on diet therapy alone, induces a coagulation activation. Acarbose, by decreasing post-meal hyperglycaemia, may be useful in reducing meal-induced activation of haemostasis in diabetic patients. more...