Policaptil Gel Retard in adult subjects with the metabolic syndrome: Efficacy, safety, and tolerability compared to metformin.

BACKGROUND: Policaptil Gel Retard® (PGR), is a new macromolecule complex based on polysaccharides slowing the rate of carbohydrate and fat absorption. It proved to significantly reduce body weight, acanthosis nigricans expression, HbA1c levels, and glucose metabolism abnormalities in obese, hyper-insulinemic adolescents. No such data are available for adults. AIM: to compare the effects of PGR vs. metformin in adult subjects with the Metabolic Syndrome (MS) and T2DM on a Low Glycemic Index diet. SUBJECTS AND METHODS: This spontaneous clinical, longitudinal, single-blind, randomized study based on a per-protocol analysis enrolled 100 outpatients with MS and T2DM consecutively referring to our clinic for three months, and randomly assigned to either the active treatment (Group A:, 6 tablets/day) or the comparator (Group B: Metformin tablets, 1500-2000 mg/day in two divided doses during the two main meals, to minimize side effects) to be taken 30 min before each main meal in equally divided doses. Serum lipid profile, anthropometry, HOMA-IR index, and tolerability parameters were evaluated before and after a 6-month follow-up period. RESULTS: all parameters improved at a similar rate in both groups but for the lipid profile, which got even better in Group A. Group A also experienced less prominent gastrointestinal side effects than its counterpart. CONCLUSION: For the first time, we showed the non-inferiority of PGR compared to metformin in obese adult subjects with the MS and T2DM as for glycemic control and a clear-cut superiority of PGR in terms of both serum lipid-lowering capacity and tolerability.

HOW to make a mix of low glycemic index flours for a good Neapolitan pizza for patients with diabetes.

BACKGROUND AND AIMS: Our recent data document that a low glycemic index (LGI) Neapolitan pizza prepared with a mix of Kamut and whole wheat flours plus Glucomannan, (i) has a lower impact on postprandial hyperglycemic spikes than pizza made of whole wheat flour, (ii) is pleasant and appreciated as traditional one and (iii) does not cause any gastro-intestinal troubles. The aim of our study was to describe the validation process underlying the identification of the right mix of those elements for a LGI pizza preventing gastro-intestinal disturbances. METHODS: we described all procedures followed to make good products with different combinations of the three components and a series of tests made by four well-experienced professional pasta-making masters, one nutritionist, five diabetologists, one nurse and twenty volunteers with T1DM. RESULTS: we could identify the best workable and most suitable flour mix to achieve both pleasant taste and low glycemic impact proving to be efficient in real-life twin paper providing results from diabetic patients. CONCLUSIONS: this kind of food will certainly help people with diabetes eat pizza without risking any serious deterioration of their own glucose control while fully enjoying socially active life.

Is pizza sutable to type 1 diabetes? A real life identification of best compromise between taste and low glycemic index in patients on insulin pump.

Opposed to whole wheat (WWP), traditional pizza (TP) is loved by patients with type 1 diabetes mellitus (T1DM) despite causing hyperglycemia. 50 well-trained T1DM patients had higher glucose levels after TP than after WWP or mixed flour pizza, which however was tasty, digestible and metabolically appropriate to break diet monotony.

Insulin-induced lypodistrophy in hemodialyzed patients: A new challenge for nephrologists?

Diabetes Mellitus (DM) is the most common cause of renal failure and ESRD all over the world, and often requires an individualized insulin treatment regimen. Malnutrition, depression-related eating behavior changes, high on-off-dialysis day-to-day glycemic variability and frequent hypoglycemic events occurring during or immediately after dialysis make it hard to identify best insulin dosage in hemodialyzed patients. This suggests a prudent attitude including non-stringent control, despite which repeated hypoglycemia quite often occurs in such patients. When looking for possible sources of hypoglycemia, health professionals too often overlook the identification of skin lipodystrophy (LD) due to an incorrect insulin injection technique. This mini-review focuses on the high frequency (57%) of LD in a cohort of 1004 insulin-treated people with DM on dialysis consecutively referring to our joint medical centers, and on its relationship with hypoglycemia and glycemic control/variability. When taking on such patients, care team members accept to face a complex disease burdened with several risk factors requiring high professional skills, and have to keep in mind also the possible presence of any LD areas eventually interfering with expected results. A timely educational intervention on the correct injection technique can help reduce the high risk of hypoglycemia and large glycemic variability in dialysed people with DM.

Skin complications of insulin injections: A case presentation and a possible explanation of hypoglycaemia.

We are willing to report the case of a woman with type 2 diabetes treated with insulin, 4 shots a day, referring to us for 2 very large pigmented abdominal lipo-hypertrophy (LH) areas due to incorrect injection technique. The ultrasound examination showed the presence offluidwithin both LH lesions. Fluid examination showed insulin concentrations 13 times higher thancirculating ones. A12-month longstructured training on correct injection techniques normalized metabolic control and took rid of all sudden severe hypoglycemic episodes and the wide glycemic variability. In fact, both LH areas disappeared became softer and slightly smaller and got fluid-free. This is the first case documenting the presence of sort of an insulin reservoir within LH lesions and fluid reabsorption can explain the disappearance of hypoglycemic episodes and the improvement of glycemic control.

Bioimpedance analysis, metabolic effects and safety of the association Berberis aristata/Bilybum marianum: a 52-week double-blind, placebo-controlled study in obese patients with type 2 diabetes.

Berberine, a quaternary isoquinoline alkaloid present in Berberis aristata, is well known in terms of cholesterol-lowering, hypoglycemic, and insulin sensitizing effects. Because of its low oral bioavailability, to improve intestinal absorption it has been recently combined with silymarin (Silybum marianum). The aim of our placebo controlled study was to evaluate the effects of its association with silymarin on abdominal fat in overweight/obese patients with type 2 diabetes mellitus (T2DM). To do so, 136 obese subjects with T2DM and metabolic syndrome were analyzed for fasting blood glucose and insulin, Insulin Resistance index according to the Homeostatic Model Assessment (HOMA-R), total, HDL and LDL cholesterol, triglycerides, uric acid, BMI, waist circumference, waist to hip ratio and underwent bioelectrical impedance to assess % of abdominal fat. All the above-mentioned parameters, as recorded at enrollment, after 6 months and at the end of the study, had significantly improved in the BBR-treated group in respect to baseline and to the control group. A validated national cardiovascular risk score also improved significantly after BBR treatment in respect to placebo. Our results point to a clinically significant effect in obese people with T2DM and metabolic syndrome. Moreover, for the first time, they provide evidence of a significant uric acid lowering activity as an additive beneficial effect of the association BBR + silymarin.

Ironic case of hepatic dysfunction following the global withdrawal of sitaxentan.

A patient with pulmonary arterial hypertension secondary to systemic sclerosis was successfully treated with sitaxentan prior to its worldwide withdrawal (because of hepatotoxicity concerns), but then ironically experienced acute hepatic dysfunction during substitute bosentan therapy, and was eventually stabilised on a phosphodiesterase-5 inhibitor.

Pulmonary hypertension in 2012: contemporary issues in diagnosis and management.

Pulmonary hypertension (PH) is a hemodynamic state of the pulmonary circulation characterised by an elevated pulmonary artery pressure. It can be the consequence of a wide variety of etiologies requiring distinct therapeutic approaches. Enormous progress has been made over the past decade in this field. A better understanding of the molecular basis of pulmonary vascular remodelling has led to development of therapies that target the specific dysfunctional pathways implicated in disease pathogenesis. Multiple classes of pulmonary specific vasodilator agents are now available for the treatment of the subgroup with pulmonary arterial hypertension (PAH), although the optimal therapeutic approach (such as combination therapy) is still evolving. With effective therapy, early detection of PAH in high-risk populations has become an important objective. The use of specific vasodilator therapy for PH secondary to left-sided heart disease or chronic lung disease is currently not supported by robust evidence. This review will summarise some of the recent advances in the field including disease classification, disease detection, and the contemporary approach to therapy.

Significance of connective tissue disease features in idiopathic interstitial pneumonia.

In idiopathic interstitial pneumonia (IIP), the significance of connective tissue disease (CTD) features in the absence of a specific CTD diagnosis remains unclear. We studied the clinical and prognostic utility of a diagnosis of undifferentiated CTD (UCTD) in patients with biopsy-proven IIP. IIP patients undergoing surgical lung biopsy (1979-2005) were studied (nonspecific interstitial pneumonia (NSIP), n = 45; idiopathic pulmonary fibrosis, n = 56). UCTD was considered present when serum autoantibodies were present and symptoms or signs suggested CTD. The relationship between UCTD and NSIP histology was evaluated. A clinical algorithm that best predicted NSIP histology was constructed using a priori variables. The prognostic utility of UCTD, and of this algorithm, was evaluated. UCTD was present in 14 (31%) NSIP and seven (13%) IPF patients. UCTD was not associated with a survival benefit. The algorithm predictive of NSIP (OR 10.4, 95% CI 3.21-33.67; p<0.0001) consisted of the absence of typical high-resolution computed tomography (HRCT) features for IPF and 1) a compatible demographic profile (females aged <50 yrs) or 2) Raynaud's phenomenon. In patients with an HRCT scan not typical for IPF, this algorithm predicted improved survival (hazard ratio 0.35, 95% CI 0.14-0.85; p = 0.02) independent of IIP severity. UCTD is associated with NSIP histology. However, the diagnostic and prognostic significance of UCTD in IIP patients remains unclear.

Elevated nocturnal desaturation index predicts mortality in interstitial lung disease.

BACKGROUND: Nocturnal desaturation may contribute to long-term pulmonary vascular stress in interstitial lung disease (ILD). We study the prevalence, severity and prognostic utility of nocturnal desaturation across ILD. METHODS: ILD patients with overnight oximetry (June 2006-August 2008) were reviewed (n = 134). Significant nocturnal desaturation was considered as > 10% of sleep with SpO2 < 90%. Desaturation index (DI) was defined as the number of desaturation events > 4%/hr. Covariates, including indices of nocturnal desaturation, were evaluated against mortality. RESULTS: Nocturnal desaturation was present in 49 (37%) patients. 31% of patients had pulmonary hypertension (PH) on echocardiography. Increased DI was associated with higher mortality independent of age, gender and BMI (HR 1.04; 95% CI 1.00, 1.06; p = 0.009). In separate models, DI and a) elevated brain natriuretic peptide (BNP; HR 1.04; 95% CI 1.00, 1.08; p = 0.04); b) moderate-severe PH on echocardiography (HR 3.15; 95% CI 1.24, 8.00; p = 0.02); and c) daytime resting SpO2 (HR 0.92; 95% CI 0.85, 0.99; p = 0.04) independently predicted mortality following adjustment for age, gender and BMI. CONCLUSION: Nocturnal desaturation is common and may be severe in ILD. Elevated nocturnal DI predicts higher mortality across ILD, independent of other vascular parameters. This finding may have important implications for the pathogenesis of PH in IPF.

Neuroprotective effects of a new skin care formulation following ultraviolet exposure.

BACKGROUND: Chronic ultraviolet (UV) exposure is a major environmental factor involved in extrinsic skin ageing (photo-ageing). Skin nerve fibres are significantly reduced in number following UV irradiation and new skincare compounds with neuroprotective effects are thus highly warranted. OBJECTIVES: We developed a new skincare formulation from a plant extract and evaluated its neuroprotective effects of ex vivo UV irradiation. MATERIALS AND METHODS: The new skincare emulsion was formulated from Echinacea purpurea extract and was enriched with antioxidants (patent no. PROV020110087075). Skin samples were obtained from 20 healthy patients enrolled for plastic surgery and were immediately treated with placebo (SPF 15) or test emulsions. Skin samples were exposed to UVA and UVB for 60 min. Nerve fibres were identified by immunofluorescence using a monoclonal antibody, anti-human CD56. Cell damage was quantified by image analysis. RESULTS: UVA and UVB significantly reduced (40-60%) densities of nerve endings in control samples treated with placebo (P < 0.001). Samples treated with test emulsion completely blocked UV-related effects on skin nerve endings. These neuroprotective effects were similarly observed regardless of age or tissue analysed (breast versus abdomen). CONCLUSIONS: Our new skincare formulation obtained from E. purpurea provides important neuroprotective effects of UV irradiation and could be used together with SPFs to prevent chronic deleterious effects of solar exposure.

Elevated brain natriuretic peptide predicts mortality in interstitial lung disease.

Elevated pulmonary vascular resistance portends a poor prognosis across interstitial lung disease (ILD), irrespective of the histospecific diagnosis. Currently, no noninvasive surrogate prognostic marker exists. We explore the prognostic value of brain natriuretic peptide (BNP) and echocardiography across ILD. ILD patients with BNP concentrations performed during 2005-2007 were reviewed (n = 90). Echocardiography tapes were reviewed by a cardiologist blinded to other results. Outcome was evaluated for survival against BNP and echocardiograph parameters. A priori threshold values and composite markers were evaluated against survival. During follow-up (20±9 months) there were 28 deaths (31%). BNP correlated with right heart echocardiographic indices, including right ventricular systolic pressure (RVSP) (R(2) = 0.18, p = 0.0002) but not with parameters of left heart function. Nonsurvivors had higher BNP and RVSP levels than survivors. BNP ≥20 pmol·L(-1) (hazard ratio (HR) 2.93, 95% CI 1.28-6.73; p = 0.01) and moderate-severe pulmonary hypertension (HR 2.53, 95% CI 1.15-5.57; p = 0.02) were associated with increased mortality, independent of age, sex and pulmonary function. Patients with BNP ≥20 pmol·L(-1) had a 14-fold increased mortality over those with BNP <4 pmol·L(-1). Increased BNP levels and/or echocardiographic markers of right ventricular dysfunction were associated with increased mortality across ILD. The link between vascular parameters and mortality supports the concept that pulmonary vascular disease contributes to the final common pathway seen across ILD.

Pulmonary hypertension in idiopathic pulmonary fibrosis: a review.

Pulmonary hypertension (PH) is a common in patients with idiopathic pulmonary fibrosis (IPF) referred for transplantation. When present, PH is associated with increased mortality, and may explain the deterioration of some patients with preserved pulmonary function. PH in IPF may develop as a consequence of, or disproportionate to the underlying fibrotic lung disease. The distinction between these two 'stages' of PH is essential as there are key differences in their pathophysiology, identification, and potential treatment options. Treatment advances in idiopathic pulmonary artery hypertension have focused attention on PH associated with underlying lung disease. We focus on pathogenetic mechanisms, identification of PH, and the potential for therapeutic intervention for PH in IPF. Although vascular ablation, and chronic hypoxia are both important in the aetiology of secondary PH, these mechanisms do not explain the development of disproportionate PH. In these patients, the early development of PH may be associated with increased fibrotic cell mediators, abnormal vasculature or response to hypoxia, seen in IPF. Nocturnal and exercise desaturation are common in IPF, and may precede and contribute to the development PH. Therapeutic options for PH in IPF are limited, and there have been no controlled trials. Successful therapeutic intervention in pulmonary arterial hypertension, has led to suggestions that therapeutic intervention with PH specific therapy may be useful. However, controlled trials are warranted before therapy can be recommended. In the design of such trials, the distinction between secondary and disproportionate PH is essential.

Pulmonary vascular resistance predicts early mortality in patients with diffuse fibrotic lung disease and suspected pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is associated with a poor prognosis in diffuse lung disease (DLD). A study was undertaken to compare the prognostic significance of invasive and non-invasive parameters in patients with DLD and suspected PH. METHODS: Hospital records of consecutive patients with DLD undergoing right heart catheterisation (RHC) were reviewed (n = 66). Mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR) and non-invasive variables were examined against early (within 12 months) and overall mortality. A priori thresholds were examined against early mortality. Relationships between mPAP, PVR and non-invasive markers were assessed. RESULTS: Fifty patients had PH on RHC (mean (SD) mPAP 33.5 (11.8) mm Hg, PVR 5.9 (4.3) Wood units (WU)). Raised PVR was strongly associated with early mortality (odds ratio (OR) 1.30; 95% confidence interval (CI) 1.11 to 1.52; p = 0.001), with PVR > or = 6.23 WU being the optimal threshold after adjustment for age, gender, composite physiological index (CPI) and diagnosis of idiopathic pulmonary fibrosis (OR 11.09; 95% CI 2.54 to 48.36; p = 0.001). Early mortality was linked, albeit less strongly, to right ventricular dilation at echocardiography, but not to other non-invasive variables or mPAP. Overall mortality was most strongly associated with increasing CPI levels. Correlations between PVR and non-invasive variables were moderate (R(2) <0.32), improving little following construction of a multivariate index which did not itself predict mortality. CONCLUSION: In severe DLD, early mortality is strongly linked to increased PVR but not to other RHC or non-invasive variables. These findings suggest that the threshold for RHC in severe DLD should be low, enabling prioritisation of aggressive treatment including lung transplantation.

Use of intravenous cyclophosphamide in known or suspected, advanced non-specific interstitial pneumonia.

BACKGROUND: In severe, progressive interstitial lung disease (ILD), specific diagnosis is often difficult, and treatment therefore empirical. An effective, rapidly acting, well-tolerated therapy is desirable. This study reviews the tolerability and efficacy of i.v. cyclophosphamide in known or suspected non-specific interstitial pneumonia (NSIP) following the introduction of an i.v. cyclophosphamide protocol. METHODS: Records of 54 patients with biopsy-proven (n = 7) or suspected NSIP, based on clinico-radiological consensus (n = 47), receiving i.v. cyclophosphamide over 2004-6 were reviewed (excluding systemic sclerosis). Lung-function trends over six months were evaluated, and comparative analysis of paired pulmonary-function before and after the start of therapy was performed. RESULTS: IV cyclophosphamide was well tolerated, with two withdrawals from therapy, and four deaths, not directly related to treatment. IV cyclophosphamide was associated with disease stability at six-months. Despite having severe, progressive disease, patients receiving i.v. cyclophosphamide had stable lung function at six months. A greater therapeutic response was associated with coexistent HRCT abnormalities indicative of organizing pneumonia. In 22 patients with paired pulmonary-function tests, pulmonary function trends were significantly improved (p = 0.03) and change in DLco differed significantly (p < 0.0001), following cyclophosphamide treatment. CONCLUSION: In the empirical treatment of advanced, rapidly progressive known or suspected NSIP, i.v. cyclophosphamide is a well tolerated, rapidly acting immunosuppressant, associated with improvement or stability in most cases.

Regional cerebral blood flow and episodic memory in Parkinson's disease: a single photon emission tomography study.

In this paper we examined 46 nondemented Parkinson's disease (PD) patients by means of perfusion single photon emission computed tomography (SPECT) and neuropsychological testing. The aim was to detect correlations of regional cerebral blood flow with episodic memory performance, using an operator-independent technique for the analysis of SPECT data. A significant positive correlation was found between prefrontal blood flow and episodic memory performances. However, age was the most important determinant of memory scores. Age also correlated significantly negatively with prefrontal perfusion. Our methodology also allowed detection of an inverse correlation of left medial temporal lobe perfusion with the memory score. This had not been found in previous studies and might indicate compensatory mechanisms in the brain of PD patients. It is concluded that episodic memory in nondemented PD patients is most dependent on the effects of aging and that the aging effects on cerebral perfusion in the PD brain parallel to a large extent the findings in normal controls.

Reference frames and haptic perception of orientation: body and head tilt effects on the oblique effect.

The aim of this study was to examine the effect of body and head tilts on the haptic oblique effect. This effect reflects the more accurate processing of vertical and horizontal orientations, relative to oblique orientations. Body or head tilts lead to a mismatch between egocentric and gravitational axes and indicate whether the haptic oblique effect is defined in an egocentric or a gravitational reference frame. The ability to reproduce principal (vertical and horizontal) and oblique orientations was studied in upright and tilted postures. Moreover, by controlling the deviation of the haptic subjective vertical provoked by postural tilt, the possible role of a subjective gravitational reference frame was tested. Results showed that the haptic reproduction of orientations was strongly affected by both the position of the body (Experiment 1) and the position of the head (Experiment 2). In particular, the classical haptic oblique effect observed in the upright posture disappeared in tilted conditions, mainly because of a decrease in the accuracy of the vertical and horizontal settings. The subjective vertical appeared to be the orientation reproduced the most accurately. These results suggest that the haptic oblique effect is not purely gravitationally or egocentrically defined but, rather, depends on a subjective gravitational reference frame that is tilted in a direction opposite to that of the head in tilted postures (Experiment 3).