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Biomedical subjects

G Valentini

Publications and source records attributed to G Valentini.

At least 19 recordsLinked to original sources

Targeting SERCA2a as an innovative approach to the therapy of congestive heart failure.

CHF prevalence is continuously increasing worldwide and maintains one of the poorest prognoses of any major disease. Abundant evidence points to derangement of Ca(2+) cycling as the primary biochemical mark of the failing myocyte. Istaroxime is a novel compound with a dual mechanism of action: inhibition of Na(+), K(+)-ATPase and stimulation of SERCA2a. The increase in cytoplasmic Ca(2+) due to Na(+), K(+)-ATPase inhibition together with greater sarcoplasmic reticulum reloading result in both increased inotropy and lusitropy. This effect is seen in normal and failing in vitro and in vivo models. Istaroxime improvement of the contraction-relaxation cycle constitutes a novel therapeutic approach to the treatment of heart failure.

Cardiotonic Agents↗

Prevention of peritoneal sclerosis: a new proposal to substitute glucose with carnitine dialysis solution (biocompatibility testing in vitro and in rabbits).

AIM: Commercial glucose peritoneal dialysis solutions expose the peritoneum to hyperosmolar glucose containing variable amounts of non-enzymic breakdown products of glucose. These solutions are toxic for the peritoneum. The aim of the present study is to compare in vitro and in vivo characteristics of a new dialysis solution containing carnitine, a naturally occurring compound, as substitute of glucose. MATERIAL AND METHODS: We compared in vitro and in the rabbit a new peritoneal dialysis solution containing carnitine, with two standard bicarbonate glucose peritoneal dialysis solutions and a solution containing icodextrin. RESULTS: In vitro and in vivo the solution containing carnitine seems to be more biocompatible than standard glucose solutions and those containing icodextrin. CONCLUSIONS: In our study the peritoneal dialysis solution containing carnitine seems to prevent the mesothelial changes observed with solutions containing glucose. Since carnitine has been extensively studied and seems to be well tolerated by hemodialysis patients, even at high doses for long periods, clinical trials in humans may be planned in the near future.

Animals↗

[The arthropathy of systemic sclerosis].

Joint involvement occurs in thirds of SSc patients during the course of the disease, but may be the onset manifestation. Arthralgias, stiffness and tendon sheath involvement constitute the most common clinical findings affecting all joints, but predominantly the fingers, wrists and ankles. The most common radiographic abnormalities in SSc patients are subcutaneous calcinosis and digital tuft resorptions, which are frequently observed at the hands. Juxtaarticular demineralisation, joint space narrowing and erosions also occur and are diagnostic challenges with rheumatoid arthritis. Flexion deformities and tendon friction rubs are more common in dcSSc; arthritis/arthralgias and radiographic abnormalities similarly affect patients from each subset. A recent classification of radiological patterns (inflammatory, degenerative, periarticular fibrotic) pointed out a greater prevalence of the fibrotic pattern at the hands and degenerative pattern at the feet.

Ankle↗

[Safety of anti-TNFα biological drugs].

OBJECTIVE: To analyse TNF-α antagonists (infliximab, etanercept e adalimumab) side effects published in the literature. METHODS: Review of published studies on this matter. RESULTS: The main side effects reported include severe infections (even though such a risk is increased per se in RA patients), possible reactivation of a previous tuberculosis, development of opportunist germs infections (mainly those with granulomas development as Aspergillus, Cryptococcus e Histoplasma). During therapy with both infliximab and etanercept development and reactivation of demyelisating diseases have been described, sometimes associated with permanent disability. Congestive heart failure, even in the absence of predisposing risk factors, development of lymphoma, mainly non-Hodgkin, and few cases of pancytopenia with hypocellular bone marrow have also been reported. CONCLUSIONS: Since comparison studies on the 3 TNF-α antagonists have not been performed yet, at present it is not possible to suggest using one drug out of the three in different clinical conditions; undoubtedly, the safety profile represents a major criterion to choose the more appropriate drug in the daily clinical practice.

Adalimumab↗

Taurine administration during lactation modifies hippocampal CA1 neurotransmission and behavioural programming in adult male mice.

Taurine plays a role in neuronal development. In this study, we examined whether postnatal taurine administration influences the long-term consequences induced by mild neonatal stressors (10 min maternal deprivation plus sham injection, applied daily to neonatal mice up to 21 days). At 30 days of age stressed mice showed higher pain threshold both in the tail-flick--which measures mostly the spinal mechanisms of pain--and in the hot-plate test--which reflects mainly the supraspinal mechanisms of pain. The latter effect was prevented completely by neonatal taurine administration, while the tail-flick test was not affected, thus suggesting that spinal pain is not sensitive to taurine treatment. At 140 days of age, mice which were stressed during the neonatal period showed consistent decrease in immobility time in forced swimming test, and taurine did not influence this parameter. At the same age, the fear/anxiety axis, measured with elevated plus maze test, did not show any consistent changes. Electrophysiological experiments in brain slices obtained from adult mice showed that input-output curves in hippocampal CA1 were increased by taurine administration in lactation. Hence, neonatal administration of taurine might permanently modify the functioning of hippocampus, a brain area which is known to be crucial for learning and memory.

Analysis of Variance↗

Factors influencing pain, physical function and social functioning in patients with osteoarthritis in southern Italy.

The aim of this study was to assess factors influencing bodily pain (BP), physical function (PF) and social functioning (SF) in patients with osteoarthritis (OA) from southern Italy A total of 1,782 patients (mean age 66.08 years, 570 men and 1,212 women) with knee, hip, spine or hand OA underwent a structured assessment comprising demographic data and the Short Form 36 (SF-36) BP, PF and SF scales. Separate multiple linear regression models were employed for statistical analysis. The mean disease duration was 9.18 years and the mean body mass index (BMI) was 27.06. The mean BP, PF and SF scores of 34.93 (SD 19.37), 63.58 (SD 26.53) and 47.89 (SD 21.83) for the study subjects were substantially lower than those expected for the general Italian population. Subjects who were younger with a shorter disease duration and lower BMI had better PF and SF Younger subjects with a lower BMI and a longer disease duration had less BP. Female sex was associated with more BP, worse SF and better PF. In conclusion, demographic and disease-related factors influence BP, PF and SF in southern Italian patients with OA.

Age Factors↗

Campylobacter jejuni enterocolitis presenting as inflammatory bowel disease.

We report a case of Campylobacter jejuni enterocolitis presenting as inflammatory bowel disease in a 19-year old woman. After a useless course of corticosteroids, ceftazidime and metronidazole, she was successfully treated with erythromicin. Campylobacter species represent an important cause of gastroenteritis in children and adults. The rate of Campylobacter isolation is 5-6 per 100,000 persons. This rate, however, grossly understimates the actual number of Campylobacter infections. In most cases, Campylobacter enteritis is a self-limiting disease, rarely associated with severe complications. Our case demonstrates the difficulty in distinguishing inflammatory bowel disease (Crohn's disease or ulcerative colitis) at onset from atypical infectious colitis. Unfortunately, corticosteroids (necessary for the treatment of inflammatory bowel disease) may exacerbate infectious etiologies. Campylobacter jejuni should be ruled out when assessing inflammatory bowel diseases at onset (as during flare-ups), especially if corticosteroids or immunosuppressive therapies are required.

Adult↗

Channel interactions with high-rate biphasic electrical stimulation in cochlear implant subjects.

Channel interactions were assessed using high-rate stimulation in cochlear implant subjects using the Ineraid electrode array. Stimulation currents were applied on one intracochlear electrode and their effects on psychophysical detection thresholds on an adjacent electrode were measured. Stimuli were trains of brief, biphasic, 50-micros/phase pulses presented at a rate of 2000 pulses per second per channel. In experiment I, we studied how the detection of a probe signal was influenced by a sub-threshold perturbation signal presented either simultaneously or non-simultaneously (with no overlap) on an adjacent electrode. Results showed that simultaneous activation led to strong channel interactions, producing threshold changes consistent with instantaneous electric field summation. Non-simultaneous activation revealed much weaker interactions, producing threshold changes of opposite sign. In experiment II, we studied how the temporal delay between perturbation and probe pulses, as well as how the level of the perturbation signal influenced non-simultaneous channel interactions. First, threshold changes when reversing the polarity of the perturbation did progressively vanish when increasing the delay between pulses. This suggested that non-overlapping stimulation of adjacent electrodes produced channel interactions that were in part due to residual polarization of the nerve membrane. Second, increasing the perturbation to supra-threshold levels produced threshold elevations that were independent of the interpulse interval. This suggested channel interactions due to neural masking. These results provide insights into the different concurrently active mechanisms of channel interactions in cochlear implant systems using this type of stimuli.

Adult↗

Blood coagulation, fibrinolysis, and markers of endothelial dysfunction in systemic sclerosis.

OBJECTIVE: To evaluate the coagulative/fibrinolytic cascade and the circulating markers of the endothelial injury in systemic sclerosis (SSc). METHOD: Plasma was obtained from 29 patients with SSc and tested for thrombin-antithrombin (TAT), fragments 1+2 (F1+2), dermatansulphate (DS), thrombomodulin (TM), lipoprotein (a) [Lp(a)], von Willebrand factor (vWF), tissue type plasminogen activator (tPA), plasminogen activator inhibitor (PAI), D-dimers, intercellular adhesion molecole-1 (ICAM-1), vascular cell adhesion molecule (VCAM), and E-selectin. The data were correlated with lung (forced vital capacity, diffusing lung capacity for carbon monoxide, vital capacity) and skin (skin score) involvement. RESULTS: Coagulation was significantly activated (increase in F1+2, P <.001; TAT, P <.01; and Lp(a), P <.05). TM was not significantly different from controls. vWF was significantly increased (P <.01), and its supranormal multimers increased in more than 50% of patients. DS was significantly increased in diffuse cutaneous SSc (P <.01). Fibrinolysis was impaired as shown by reduced D-dimers (P <.01) and decreased levels of PAI (P < 0.01). The markers of endothelial injury were also significantly elevated. DS correlated significantly with forced vital capacity (P <.01) and forced vital capacity ratio (P <.01). CONCLUSION: Injury to the endothelium reduces endothelial function, as suggested by impairment of fibrinolysis and activation of the coagulative pathway. The loss of the balance between fibrinolysis and coagulation contributes to vessel engulfment with fibrin and breakdown of vessel patency. The increase of circulating DS suggests that this factor may be a new marker of endothelial injury.

Adult↗

Systemic sclerosis could mask the presentation of psoriasis in a patient with symptomatic and bilateral sacroiliitis.

Psoriasis is rarely associated with systemic sclerosis (SSc), and sacroiliitis associated to Connective Tissue Diseases is also rather rare. In this report we describe a case of a young woman with SSc who developed symptomatic and bilateral sacroiliitis. The clinical pattern of sacroiliac involvement of this patient resembles that of psoriatic sacroiliitis. HLA typing was compatible with both SSc and psoriasis. Psoriatic sacroiliitis could not be diagnosed, but, on the basis of these observations, the patient described could represent a case of PsA without psoriasis. and psoriatic cutaneous involvement masked by the presence of SSc.

Adult↗

Correlations of Y chromosome microchimerism with disease activity in patients with SLE: analysis of preliminary data.

BACKGROUND: Recently it has been suggested that microchimerism may have a significant role in the aetiopathogenesis of some autoimmune diseases. OBJECTIVES: To evaluate the incidence of microchimerism in systemic lupus erythematosus (SLE), to quantify the phenomenon, to evaluate changes of microchimerism during follow up, and to correlate these data with clinical and laboratory variables. METHODS: Patients were selected for the study on the basis of the following criteria: (a) pregnancy with at least one male offspring; (b) no history of abortion and blood transfusion. Microchimerism was detected using a competitive nested polymerase chain reaction for a specific Y chromosome sequence and an internal competitor designed ad hoc. Disease activity and organ involvement were also evaluated. RESULTS: Sixty samples from 22 patients with SLE and 24 healthy controls were examined. Microchimerism was seen in 11 (50%) patients and 12 (50%) controls. The mean number of male equivalent cells was 2.4 cells/100 000 (range 0.1-17) in patients with SLE and 2.5 (range 0.2-1.8) in healthy controls. No differences in the incidence of microchimerism or in the number of microchimeric cells were found between patients and healthy controls. Patients with a history of lupus nephritis had a higher mean number of fetal cells than patients with no such history. Disease activity did not appear to correlate with microchimerism. CONCLUSIONS: The preliminary data suggest that microchimerism does not interfere with the disease course of SLE, although further analysis on larger groups will be necessary to confirm these observations.

Adolescent↗

European Scleroderma Study Group to define disease activity criteria for systemic sclerosis. III. Assessment of the construct validity of the preliminary activity criteria.

OBJECTIVE: To further assess the construct validity of the three European Scleroderma Study Group (EScSG) preliminary activity indices for systemic sclerosis (SSc): for SSc as a whole, for diffuse SSc (dcSSc), and for limited SSc (lcSSc). METHODS: 30/290 SSc clinical charts collected for the EScSG study used to develop activity criteria for SSc were selected and sent to four clinical experts in SSc. The experts ranked the charts from 1 to 30 (1=lowest activity, 30=highest activity). The relationships among the ranks given by each investigator and each of the three scores, and between any two of the ranks were investigated. RESULTS: A consistently significant correlation (r(s)=0.530-0.712) was found between the ranks given by each of the four investigators and the index for the entire patient group. A similar level of agreement was detected between each couple of the four experts (r(s)=0.428-0.720). Moreover, the ranks given in patients with an index >3 were significantly higher than those given for patients with an index < or =3. This cut off point had previously been shown to best discriminate patients with active disease. CONCLUSIONS: Of the originally developed activity indexes, the whole series index has been externally validated. The index comprises the first preliminary, but necessary, groundwork to improve the concept of disease activity in SSc, which is still ill defined. It can be used as a preliminary activity index in clinical investigational studies.

Humans↗

An update on the medical treatment of Crohn's disease.

Crohn's disease (CD) is a chronic transmural inflammation that may involve any part of the alimentary tract. The affected patients show peculiar metabolic characteristics; they often have a reduced body weight, due to reduction of lipid stores (in spite of lean mass depletion) and an increased utilization of lipids as fuel substrate. An alteration of nutritional status, up to real malnutrition, is common in CD and malnutrition's effects influence the course of disease, acting as independent factors. We will give a description of the main pharmacological approaches in CD management; the first line therapy for CD patients remains the combinations of aminosalicylates, antibiotics, corticosteroids and immunomodulatory agents. The development of new biological agents for the treatment of inflammatory bowel diseases has added to the growing armamentarium of available therapy. We also will explain the importance of enteral nutrition, whose importance goes over the simple amelioration of nutritional status, especially in childhood CD, where it has shown to be as effective as traditional therapy.

Adjuvants, Immunologic↗

Hepatopulmonary syndrome. A review of the literature.

The majority of cirrhotic patients present dyspnea, but most of the time this is a consequence of ascites, hepatic hydrothorax or cardiopulmonary disease. Very few of these patients undergo the hepatopulmonary syndrome, an infrequent complication of chronic liver disease, especially when associated with portal hypertension and cirrhosis. Hepatopulmonary syndrome is characterised by dyspnea and, consequently, arterial hypoxemia, due to intrapulmonary vasodilation and shunting. The real pathogenesis of this vasodilation is still unknown, although many hypotheses have been suggested. Furthermore, no medical therapy appears to be really useful in the treatment of hepatopulmonary syndrome. At the present time, the only treatment that is efficacious for the resolution, or for the improvement of blood gas oxygenation abnormalities, is orthotopic liver transplantation.

Chronic Disease↗