Development and validation of a delirium risk assessment tool in older patients admitted to the Emergency Department Observation Unit.

BACKGROUND: Delirium is frequent though undetected in older patients admitted to the Emergency Department (ED). AIMS: To develop and validate a delirium risk assessment tool for older persons admitted to the ED Observation Unit (OU). METHODS: We used data from two samples of 65 + year-old patients, one admitted to the ED of Brescia Hospital (n = 257) and one to the ED of Desio Hospital (n = 107), Italy. Data from Brescia were used as training sample, those collected in Desio as testing one. Delirium was assessed using the 4AT and patients' characteristic were retrieved from medical charts. Variables found to be associated with delirium in the training sample were tested for the creation of a delirium risk assessment tool. The resulting tool's performances were assessed in the testing subsample. RESULTS: Of all possible scores tested, the combination with the highest discriminative ability in the training sample included: age ≥ 75 years, dementia diagnosis, chronic use of neuroleptics, and hearing impairment. The delirium score exhibited an AUC of 0.874 and 0.893 in the training and testing samples, respectively. For a 1-point increase in the score, the odds of delirium increased more than twice in both samples. DISCUSSION: We propose a delirium risk assessing tool that includes variables that can be easily collected at ED admission and that can be calculated rapidly. CONCLUSION: A risk assessment tool could help improving delirium detection in older persons referring to ED.

Development of a multi-layer high-efficiency GEM-based neutron detector for spallation sources.

Neutron detection is nowadays mostly based on 3He gas detectors, but its shortage and the continuous upgrades of the neutron facilities require new devices to perform experiments with maximum performances. This work presents a new detector based on the Gas Electron Multiplier (GEM) combined with several boron layers. This detector combines the features of GEM technology with the properties of boron as a neutron converter and the device is produced to sustain high neutron fluxes with high detection efficiency. The detector has been characterised at the ISIS Pulsed Neutron and Muon Source (UK). Based on the analysis of our results, the detector has shown a good response to thermal and epithermal neutrons reaching a detection efficiency of 16% at 1.8 Å (25 meV). The good detection efficiency (even increasable with the addition of further boron GEM foils) and the good time resolution, make the detector a unique device for the neutron techniques. In particular, its use can easily be envisaged in techniques involving neutron transmission measurements, that require high fluxes impinging on the detectors, with the added bonus of a 2D-resolved capability due to the padded anode.

Biological activity of three alkyl cinnamates on young larvae of Tuta absoluta.

The "tomato moth," Tuto absoluta (Meyrick) (Lepidoptera: Gelechiidae), is a neotropical oligophagous insect considered a key pest of tomato crops. It was detected in Europe seven years ago and quickly spread to several regions of Asia and North Africa. In Argentina, its control is done by chemical pesticides mainly. The indiscriminate use of chemical broad spectrum pesticides have caused several problems in the control of this pest due to resistance mechanism involved to several insecticides including pyrethroids, organophosphates and biopesticides. In this context, the searching and evaluation of new compounds- compatible with integrated pest management programs- has become relevant. Within the phenylpropanoids, alkyl cinnamates, whether natural or synthetic, have been reported with biological activity: repellence, antifeedant and insecticide. Therefore, the cinnamates could be a valuable alternative to replace the conventional insecticides. The aim of this work was to study the antifeedant effect of three alkyl cinnamates (methyl, ethyl and propyl cinnamate) on the consumption rate patterns of second instar larvae of T. absoluta. A series of concentrations of each compound (100, 250 and 500 micrograms/milliliter) were prepared using acetone (analytical grade) - distilled water as solvent and a surfactant (Tween 80) was added to each solution to improve the wet of leaves. Tomato leaf disks of 2 cm diameter were treated by immersion in each solution during 15 seconds. Afterward, the treated discs were dried under fume hood and each disk was placed in a plastic capsule. A larva with 6-8 hours of starvation was added to each experimental unit. Each treatment was replicated between 24-30 times. The area consumed by each larva was measured after 24, 48 and 72 hours post-treatment. We also evaluated development time, weight of the pupa, adult emergence, fecundity and fertility as sublethal effects. The results were analyzed using ANOVA test. None of the compounds tested at the aforementioned concentrations exhibited insecticidal effect. However, ethyl cinnamate showed a strong antifeedant effect. The results observed on the leaf consumption and other sublethal effects assessed will be discussed. According to these preliminary results, further studies are needed to complete its toxicological profile by other exposure methods.

Canine gastrointestinal stromal tumours treated with surgery and imatinib mesylate: three cases (2018-2020).

OBJECTIVES: Gastrointestinal stromal tumours (GISTs) are described in dogs and are histologically diagnosed with the aid of immunohistochemistry to allow differentiation from leiomyomas/leiomyosarcomas. These tumours express c-kit and in some cases could harbour mutations in KIT coding gene. MATERIALS AND METHODS: Dogs with a diagnosis of GIST previously confirmed with histopathology and immunohistochemistry were considered for inclusion. Medical records were reviewed for clinical signs at presentation, results of diagnostic tests, tumour location and treatment. To be included, patients had to undergo staging procedures and treatment with imatinib alone or in combination with surgery. Immunohistochemistry and KIT mutational analysis were performed assessing all included cases. RESULTS: Three cases were included. All cases underwent staging procedures and surgical excision. Tumours were located in the stomach (two cases) or caecum (one case). KIT mutational status was assessed and the presence of a 54-base pair deletion in exon 11 was identified in one case. Following surgery, imatinib was used to treat recurrent, metastatic or residual disease and resulted in complete response and stable disease in the macroscopic setting and no evidence of recurrence in the microscopic setting. Follow-up time was 890, 120 and 352 days, respectively. CLINICAL SIGNIFICANCE: Surgical and medical treatment resulted in a positive outcome in these cases of canine GIST. Imatinib treatment was well tolerated and resulted in a measurable response and a low spectrum of toxicities. Further studies on the tolerability and efficacy of imatinib in solid tumours and GIST are warranted to define its effectiveness and safety.

Retrospective analysis of outcome and prognostic factors of subcutaneous mast cell tumours in dogs undergoing surgery with or without adjuvant treatment.

Subcutaneous mast cell tumours (SC MCTs) can display a different biological behaviour in dogs when compared to their cutaneous counterpart. There is a paucity of information with regards to the outcome of dogs with SC MCTs treated with surgery and/or receiving adjuvant chemotherapy. The aim of this study was to retrospectively review the outcome of dogs with surgically excised SC MCTs undergoing adjuvant treatment or not. A secondary aim was to assess prognostic factors in the same group. Fifty-two cases were included. Recurrence rate was 15% and 63% of evaluated lymph nodes were consistent with early or overt metastasis. Median survival time (range 83-1357 days) and median time to progression (range 14-1357 days) were not reached. Factors predictive of shorter overall survival time included increasing age (HR 1.29, 95% CI 1.06-1.55, p = .0092), presence of clinical signs at presentation (HR 10.44, 95% CI 2.69-40.52, p = .0007), mitotic count >4 (HR 8.69, 95% CI 2.55-29.55, p = 0.0005), presence of multinucleation (HR 4.21, 95% CI 1.35-13.18, p = .0135), use of neoadjuvant and adjuvant chemotherapy (HR 7.16, 95% CI 1.26-40.73, p = .0266). The same factors, together with increasing tumour dimensions, were predictive for shorter progression-free survival (PFS), including increasing age (p = .0012), presence of clinical signs at presentation (p = .0045), increasing tumour dimensions (p = .0004), MC > 4 (p = .0004), presence of multinucleation (p = .0282), use of neoadjuvant and adjuvant chemotherapy (p = .0485). No variables remained significant for overall survival using multivariate analysis. There was a longer survival in cases where chemotherapy was not required (HR 0.14, 95% CI 0.03-0.68, p = .0148), and this variable remained significant for PFS on multivariate analysis (HR 0.13, 95% CI 0.02-0.76, p = .02). In conclusion, our study suggests that dogs with SC MCTs, in the absence of negative prognostic factors, may have a prolonged survival when treated with surgery alone. Further studies are needed to clarify the role of adjuvant treatment for biologically aggressive SC MCTs in dogs.

Percutaneous ultrasound-guided microwave ablation for treatment of hepatocellular carcinomas in dogs: four cases (2019-2020).

OBJECTIVES: To describe ultrasound-guided microwave ablation as a minimally invasive treatment option for primary or metastatic hepatocellular carcinomas. METHODS: Four client-owned dogs underwent percutaneous ultrasound-guided microwave ablation of three primary and one metastatic hepatocellular carcinoma, diagnosed on cytology/histopathology. In each case, multiple ultrasound-guided thermal lesions were created in a 10 to 40 minutes ablation at 30 to 35 W. Real-time monitoring was performed using 10 MHz diagnostic ultrasound transducers. The procedures were performed without complication and CT scans or abdominal ultrasounds were repeated immediately after. Patients were discharged on oral analgesia on the same day or 24 hours later. RESULTS: Hepatocellular carcinomas were successfully ablated, which in some cases resulted in an improvement in clinical signs and laboratory values. The patients were followed up for a time ranging between 39 and 649 days and no evidence of disease progression was found. Three out of four patients are still alive at the time of writing. CLINICAL SIGNIFICANCE: In these four patients, minimally invasive ultrasound-guided microwave ablation was feasible and resulted in no immediate complications. Regular imaging follow-up is recommended after the procedure and further studies on microwave ablation are warranted to establish its effectiveness in dogs with hepatocellular carcinomas.

Vibrational spectroscopy to study ancient Roman funerary practices at the "Hypogeum of the Garlands" (Italy).

The "Hypogeum of the Garlands" is a sepulchral site, recently found in Grottaferrata (Lazio, Italy), dating back to the first-second century AD. Two sarcophagi were discovered inside, hosting the human remains of Aebutia Quarta, a rich Roman woman, and her son Carvilius Gemellus. While the body of Carvilius is exceptionally well-preserved, following its embalming and perfect sealing of the sarcophagus, in the case of Aebutia only the bones were preserved because of the sarcophagus's seal breaking down, although she was covered with perfectly preserved flower garlands. Embalming of the body was a rare ritual in the Imperial Roman times when corpses were more often cremated. The remains of Aebutia showed possible traces of heating. Burned bones from a third individual were discovered on the chamber's floor and preliminary anthropological survey showed that this individual was a male of 40-50 years old. Here, a combination of spectroscopic techniques, including non-destructive inelastic neutron scattering and Raman spectroscopy, and minimally destructive Fourier transform infrared spectroscopy, were applied to the analysis of these bone samples to give information about ancient Roman funerary practices. The temperature and burning conditions were thus determined, showing that Aebutia Quarta was exposed to mild temperatures (200 °C) only in the upper part of the body, while the third individual was likely cremated as its bones were exposed to temperatures up to 900 °C in quasi-anaerobic conditions.

A food borne outbreak of Salmonella enterica serotype Brandenburg as a hint to compare human, animal and food isolates identified in the years 2005-2009 in Italy.

INTRODUCTION: There are only a few reported cases of Salmonella enterica serotype Brandenburg foodborne outbreaks in the literature. In Italy Brandenburg is consistently present among the top ten serotypes from human source, but at low prevalences. MATERIALS AND METHODS: Fifty-five S. Brandenburg isolates from human, animal, environmental and food sources, including twelve isolates from a foodborne outbreak, were genotyped by Pulsed-Field Gel Electrophoresis (PFGE). RESULTS AND DISCUSSION: Eight pulsogroups and 19 pulsotypes were detected, with a unique pulsotype being attributed to the outbreak strains. Molecular subtyping can reliably complement the epidemiological investigations. Moreover, mapping molecular types of Salmonella isolates from human and non-human source may greatly contribute to risk assessment, by tracking possible animal sources, so improving cost-effectiveness of the prevention and control strategies.

Tolerability and outcome of palliative treatment for metastatic pulmonary carcinoma in cats.

OBJECTIVES: Pulmonary carcinoma is uncommon in cats and reporting of outcomes following medical treatment is limited, especially in presence of metastases. The aim of this study was to describe the outcome of cats affected by metastatic primary pulmonary carcinoma and to evaluate the tolerability of palliative treatment in this patient population. MATERIALS AND METHODS: Medical records were searched for cats with a cytological or histopathological diagnosis of primary pulmonary carcinoma and evidence of metastatic disease. Cats were treated with antineoplastic agents, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) or received no systemic treatment. Cases in which thoracic CT was not performed, and those lacking definitive diagnosis by cytology or histopathology or receiving curative-intent surgery were excluded. RESULTS: Thirty-four cats were identified: 18 were treated with antineoplastic agents and 16 received corticosteroids, NSAIDs or no treatment. Presenting clinical signs included coughing (53%), tachypnoea (26%), gastrointestinal signs (35%) and lethargy (18%). CT scan identified metastases to the lung parenchyma in all cases and additional metastatic lesions in 10 of 34 (59%) cases; pleural effusion was detected in 11 cases (32%). The overall median survival time for all cats was 64 days [range 1-1352 days; 95% confidence interval (CI) 48-164]. Presence of respiratory signs at presentation was the only factor influencing survival in the multivariable analysis. CLINICAL SIGNIFICANCE: Medical treatment was well tolerated and appeared to palliate clinical signs in cats with metastatic pulmonary carcinoma, albeit with a modest duration and short overall survival. The role and benefit of chemotherapy/antineoplastic agents versus conventional palliative drugs in this setting remains unclear.

MWCNT/rGO/natural rubber latex dispersions for innovative, piezo-resistive and cement-based composite sensors.

The present study is focused on the development and characterization of innovative cementitious-based composite sensors. In particular, multifunctional cement mortars with enhanced piezoresistive properties are realized by exploiting the concept of confinement of Multiwall Carbon Nanotubes (MWCNTs) and reduced Graphene Oxide (rGO) in a three-dimensional percolated network through the use of a natural-rubber latex aqueous dispersion. The manufactured cement-based composites were characterized by means of Inelastic Neutron Scattering to assess the hydration reactions and the interactions between natural rubber and the hydrated-cement phases and by Scanning Electron Microscopy and X-Ray diffraction to evaluate the morphological and mineralogical structure, respectively. Piezo-resistive properties to assess electro-mechanical behavior in strain condition are also measured. The results show that the presence of natural rubber latex allows to obtain a three-dimensional rGO/MWCNTs segregate structure which catalyzes the formation of hydrated phases of the cement and increases the piezo-resistive sensitivity of mortar composites, representing a reliable approach in developing innovative mortar-based piezoresistive strain sensors.

Early cardiovascular involvement in chronic obstructive pulmonary disease.

Cardiovascular (CV) disease represents a considerable risk factor in terms of both morbidity and mortality in elderly patients with chronic obstructive pulmonary disease (COPD). In fact, there is a considerable evidence of this association: for only 20 years forced expiratory volume in 1 second (FEV1) has been considered as predictive of cardiovascular mortality especially in elderly patients. At present, the emerging evidence suggests that hypoxia, systemic inflammation, oxidative stress may cause an early sub-clinical cardiovascular involvement in patients with COPD. Aging is a selective process dramatically affecting certain portions of the cardiovascular system for example: diminished beta-adrenergic responsiveness, increased myocardial and vascular stiffness, decreased arterial baroreflex, vagal outflow and compromission of diastolic function. The nature of these interactions is complex and involves not only mechanisms of aging but also multiple defined and undefined (e.g., genetic) risk factors. Cardiovascular diseases are the main causes of mortality among the subjects with impaired lung function. Even mild reductions in expiratory flow volumes amplify the risk of ischemic heart diseases, strokes, and sudden cardiac deaths 2- to 3-fold, independent of other risk factors. The mechanism or mechanisms responsible for this association, however, remain largely unknown.

Ballast water management system: Assessment of chemical quality status of several ports in Adriatic Sea.

Oxidant treatment of ballast water (BW) is commonly used in BW systems in order to minimize the transport of alien species. The release of disinfection by-products (DBPs) associated to the treatment of BW and cross-contamination of butyltin (BT) compounds through BW discharge is a topic of environmental concern. A chemical port baseline survey has been conducted in seven ports of the Adriatic Sea. Analysis have been performed on transplanted mussels, surface sediment, seawater, BW. Results showed an evidence of BT contamination, particularly in sediments, probably related to their illegal usage or to intensive shipping activities. Therefore, BW may act as a vector and contribute to re-buildup of BT contamination in the coastal regions. A baseline set of data concerning DBPs is provided, showing the preferential distribution of these compounds in the marine environment that will be useful for future considerations on monitoring and assessment of chemical contamination associated with BW.

Clinicopathological features and outcome for dogs with mast cell tumors and bone marrow involvement.

BACKGROUND: Mast cell tumors (MCTs) with bone marrow (BM) involvement are poorly documented in dogs and are associated with a poor prognosis. Successful treatment strategies have not been described. HYPOTHESIS: Clinicopathologic findings of affected dogs are not specific. Administration of lomustine or imatinib is beneficial. ANIMALS: Fourteen dogs with MCT and BM involvement. METHODS: Clinical and laboratory evaluations were performed in each dog on admission and during follow-up. All dogs received prednisone. Additionally, 8 dogs received lomustine and 3 dogs received imatinib. Imatinib was administered if tumor-associated tyrosine kinase KIT was aberrant. RESULTS: On admission, 11 dogs had a single cutaneous nodule and 3 dogs had multiple nodules. Involvement of regional lymph nodes, liver, or spleen was observed in each dog. BM infiltration with mast cells (MCs) was observed in all dogs. On CBC, nonregenerative anemia, leukopenia, or thrombocytopenia was common. Four dogs had circulating MCs. Increased alkaline phosphatase or alanine transferase activity was observed in 12 and 10 dogs, respectively. Treatment with lomustine induced partial remission in 1 of 8 dogs. Median survival time was 43 days (range, 14-57). Dogs on imatinib experienced complete remission. Two dogs survived for 117 and 159 days, and the third was alive after 75 days. Dogs treated symptomatically did not improve and were euthanized after 1, 14, and 32 days. CONCLUSIONS AND CLINICAL IMPORTANCE: A combination of clinical and laboratory evaluation helps in identifying dogs with MCT and BM infiltration. Administration of lomustine is not helpful in affected dogs. The beneficial effect of imatinib warrants further investigation.

Treatment of idiopathic chylothorax in 14 dogs by ligation of the thoracic duct and partial pericardiectomy.

The outcome and complications associated with thoracic duct ligation combined with partial pericardiectomy in 14 dogs with idiopathic chylothorax were investigated retrospectively. Nine of the dogs were treated in the uk and five in Italy. All of them were reassessed clinically four weeks after surgery and the respiratory function and any pleural fluid accumulation were evaluated; they were followed up by telephone contact for at least six months. Eleven of the dogs were clinically normal and had no radiographic signs of pleural effusion when reassessed after four weeks. Two showed radiographic signs of a minor accumulation of pleural fluid but were clinically normal; when reassessed after three months they showed similar radiographic signs and clinical findings; but after four months there was no evidence of pleural effusion. One dog had a major complication that required a second surgical intervention.

Combined caudal-superficial-epigastric axial pattern flap and full-thickness buccal mucosa graft for single-stage preputial reconstruction in six dogs.

OBJECTIVE: To describe the use of a caudal superficial epigastric flap in combination with a full-thickness oral mucosal/submucosal graft for single-stage reconstruction of extensive preputial defects in dogs. MATERIALS AND METHODS: Medical records of dogs with extensive preputial defects either of traumatic origin or derived from tumour excision were reviewed. In all dogs, the prepuce was reconstructed using a full-thickness oral mucosal/submucosal graft combined with a caudal superficial epigastric axial pattern flap during a single surgical procedure. Outcome was assessed by routine clinical examinations for 6 months postoperatively, and through telephone follow-up thereafter. RESULTS: Six dogs were included. The caudal superficial epigastric axial pattern flap healed without complications in all dogs, while the full-thickness oral mucosal/submucosal graft failed in one dog. In this individual the skin flap underwent contracture 30 days after surgery and preputial advancement was required. One dog showed postoperative discomfort during urination, which was successfully managed with a Foley catheter and analgesic administration. Three dogs developed paraphimosis at 30, 80 and 90 days, respectively, and required further surgery. Long-term results were good in all dogs. CLINICAL SIGNIFICANCE: The use of a full-thickness oral mucosal/submucosal graft combined with a caudal superficial epigastric axial pattern flap is feasible for single-stage preputial reconstruction in dogs. Attention should be paid to create a sufficiently large preputial opening, in order to prevent paraphimosis.

Retrospective evaluation of COX-2 expression, histological and clinical factors as prognostic indicators in dogs with renal cell carcinomas undergoing nephrectomy.

Limited veterinary literature is available regarding prognostic markers for canine renal cell carcinoma (CRCC). We retrospectively evaluated COX-2 expression, histological and clinical features associated with prognosis of CRCC. Sixty-four cases post-nephrectomy were included, 54 had histopathological assessment and 30 had COX-2 immunostaining performed. Eight dogs (13%) had metastatic disease at initial diagnosis. Twenty-seven dogs (42%) received adjuvant therapy after nephrectomy. On univariate analysis, COX-2 expression, mitotic index (MI), histologic type, vascular invasion, neoplastic invasiveness and metastasis at diagnosis were significantly associated with overall median survival time (MST). COX-2 score (COX-2 score > 3 MST 420 days versus 1176 days if COX-2 score <3; P = 0.011) and MI (MI > 30 MST 120 days versus 540 days for MI < 30; P = 0.003) were the only variables associated with CRCC outcome on multivariate analysis. The addition of MI and COX-2 immunostaining to standard histopathological evaluation would help predicting outcome in CRCC patients.

Canine pancreatic islet cell tumours secreting insulin-like growth factor type 2: a rare entity.

Insulin-like growth factor type II (IGF-II) is the main cause of non-islet cell tumour hypoglycaemia (NICTH) and insulin is thought to be the only factor causing hypoglycaemia in insulinomas. However, two case reports of pancreatic neuroendocrine tumours (PNETs) producing IGF-II have been previously published: a human and a canine patient. In this study, we investigated clinical, histopathological, immunohistochemical and ultrastructural features, and biological behaviour of canine pancreatic IGF-II-omas, a subgroup of PNETs that has not been previously characterized. Case records of 58 dogs with confirmed PNETs and hypoglycaemia were reviewed: six patients were affected by IGF-II-omas. Surgery was performed in all cases and two dogs had metastases. Four patients remained alive and in remission at 370, 440, 560 and 890 days post-diagnosis; two died of non-tumour-related causes. IGF-II-omas can be differentiated from insulinomas through hypoinsulinaemia, IGF-II positive and insulin negative immunostaining. The prevalence of this neoplasia is low, accounting for just 6% of PNETs.

Short-term administration of captopril and nifedipine and exercise-induced albuminuria in normotensive diabetic patients with early-stage nephropathy.

Recent studies have demonstrated that short-term angiotensin converting enzyme (ACE) inhibition with captopril can reduce urinary albumin excretion rate (UAER) after exercise in normotensive diabetic patients with early-stage nephropathy. The aim of this study was to investigate whether this effect of ACE inhibition was due to a systemic hypotensive action or a specific action at the intrarenal level. Thus, we compared the acute effects of captopril and the Ca2(+)-channel blocker nifedipine on exercise-induced UAER in normotensive (blood pressure less than 165/95 mmHg) diabetic patients who were normoalbuminuric or microalbuminuric at rest (stage 2 or 3 of diabetic nephropathy). Twenty-five stage 2 diabetic nephropathy patients, 39 stage 3 diabetic nephropathy patients, and 12 nondiabetic subjects performed five submaximal cycloergometric exercises (90% of theoretical heart rate) on nonconsecutive days. The first two exercises were performed in basal conditions; the next three exercises were performed 24 h after administration of captopril (25 mg twice daily) or nifedipine AR (20 mg twice daily) or placebo (1 tablet twice daily) according to a randomized double-blind crossover trial. After placebo, blood pressure and UAER did not change at rest or 1 h after exercise. After captopril, blood pressure at rest and during exercise was similar to that observed after placebo. UAER at rest was not modified, whereas 1 h after exercise, it was significantly decreased both in stage 2 and stage 3 diabetic nephropathy patients (P less than 0.001). After nifedipine, blood pressure decreased significantly at rest and during exercise in respect to placebo and captopril. UAER at rest did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term treatment with the dual antithromboxane agent picotamide decreases microalbuminuria in normotensive type 2 diabetic patients.

Picotamide both inhibits thromboxane synthetase and acts as a thromboxane antagonist at the receptor level. We investigated the long-term effect of picotamide on urinary albumin excretion (UAE) at rest and induced by exercise in 30 type 2 diabetic patients who were normotensive and had microalbuminuria while at rest. The subjects of our study had a mean age of 52.5 +/- 1.6 years, BMI of 28.5 +/- 0.7 kg/m2, diabetes duration of 9.1 +/- 1.8 years, and HbA1c of 7.0 +/- 0.8%. The study was a randomized double-blind placebo-controlled trial. The patients were randomly allocated to receive for 1 year either picotamide, 300 mg, 3 tablets/day, or placebo, 3 tablets/day. The patients were asked to visit our outpatient clinic after 1, 3, 6, 9, and 12 months of treatment. At all times, blood pressure, microalbuminuria at rest, blood glucose, serum creatinine, serum picotamide, and creatinine clearance were measured; at baseline and after 6 and 12 months, all patients underwent submaximal physical exercise. After 6 months of picotamide, baseline and exercise-induced microalbuminuria were significantly decreased (up to one-third) as compared with the baseline and placebo level, with no further drops at month 12 of picotamide treatment. On placebo treatment, UAE at rest and after exercise was slightly increased compared with baseline values. The effects of picotamide occurred without significant side effects or changes in either blood pressure levels or glycometabolic control. Our study is the first long-term intervention trial in type 2 diabetes showing that an antithromboxane agent is able to decrease microalbuminuria, which in this disease is a dual marker of macro- and microangiopathy. Our findings suggest an important role for thromboxane in the pathophysiology of microalbuminuria in diabetes; moreover, we hypothesize that antithromboxane agents may have a place in the treatment/prevention of both macro- and microvascular complications in type 2 diabetic patients.

Picotamide, a dual TXB synthetase inhibitor and TXB receptor antagonist, reduces exercise-induced albuminuria in microalbuminuric patients with NIDDM.

We investigated the short-term effect of the TXB inhibitor picotamide on albuminuria induced by exercise in 15 microalbuminuric (i.e., with UAE at rest between 20 and 200 micrograms/min) type II diabetic patients (12 men and 3 women, age 56 +/- 2, BMI 28 +/- 1 kg/m2) and in six normal age-matched control subjects. The diabetic subjects performed five submaximal exercise tests (90% of theoretical heart rate) on a cycle ergometer: the first two under basal conditions; the third and fifth after subjects had received picotamide (900 mg/day) or placebo (3 tablets/day) for 10 days; the fourth exercise always was performed after 10 days of wash-out. Control subjects performed two exercises: the first in baseline conditions and the second after 10 days of picotamide administration (900 mg/day). When diabetic patients were untreated, a significant (P < 0.05) increase in UAE with respect to baseline levels was observed immediately after and 1 h after the exercise test. After picotamide administration, UAE significantly decreased (P < 0.05) immediately after and 1 h after exercise, as compared with diabetic patients given a placebo. In normal subjects, exercise was followed by a slight increase in UAE, which was not significantly affected by picotamide administration. Our results show that short-term administration of picotamide is associated with a reduction in UAE after exercise in type II diabetes patients with microalbuminuria while at rest. Picotamide, a TXB synthetase and receptor inhibitor, may decrease exercise-induced albuminuria in diabetic patients through a reduction in circulating TXB levels and inhibition of TXB action, which in turn may act by lowering glomerular capillary hydraulic pressure.