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A recent Italian study examined the immune response to the COVID-19 vaccine among psoriatic patients receiving biological therapy. The study included 346 psoriatic patients and 151 controls who received two doses of the vaccine and were tested for antibodies. The results showed that both groups had a strong antibody response, with no significant difference between patients and controls. Mild adverse events were reported by about one-fourth of participants, and no serious adverse events were reported. The study also found that the type of vaccine administered was associated with antibody levels, with higher levels observed in those vaccinated with Janssen and lower levels in those vaccinated with AstraZeneca. However, the number of subjects who received these vaccines was limited. The study suggests that COVID-19 vaccinations are effective and safe for psoriatic patients undergoing biological treatments. [Extracted from the article]

Blue nevi are a heterogeneous group of lesions that can display a variety of different clinicopathological characteristics. Although attempts are made to classify each lesion into defined subtypes, there can be overlap between the subtypes. The clinical, dermoscopic and histolopathologic features of a case of proliferative nodule arising within blue nevus is discussed. Running title: Blue nevi are an heterogeneous group of melanocytic lesions blue tinctorial properties. Proliferative nodules are rare benign lesions often present at birth as a component of a large congenital melanocytic nevi, congenital or acquired nevi. We first report a case of proliferative nodule arising within blue nevus. [ABSTRACT FROM AUTHOR]

Psoriasis is a immune-mediated, chronic, inflammatory skin disease. In HIV positive (HIV+) patients we usually observe more serious clinical features and recalcitrant course. Furthermore, therapeutic management of HIV+ patient is complex and requires collaboration with the infectious disease specialist. We report the case of a patient affected by severe psoriasis who contracted HIV infection during biological therapy and, subsequently, succesfully treated with ixekizumab. [ABSTRACT FROM AUTHOR]

Background. Psoriasis is a multifactorial chronic inflammatory skin disease characterized by erythemato-squamous lesions with a chronic relapsing course. The desease clinical activity (PASI) and the patient's quality of life (DLQI) are the main elements to assess for setting up a correct therapeutic management. Objective. The aim of the study was to evaluate the management of the patient with moderate-severe psoriasis in therapy with biological drugs and to establish the difference in the achievement of PASI 90 and DLQI 0-1 between a group of patients treated with only biological drugs and a group of patients receiving biologic therapy in combination with a topical ointment. Methods. we conducted a prospective, observational real-life study enrolling 60 patients with moderate to severe psoriasis and divided in two groups: Group A patients treated with biological drugs, Group B patiens treated with biological drugs in association with an ointment composed of betamethasone, salicylic acid and ammonium sulphoichtyolate, applied 2 times a day. PASI and DLQI were evaluated at study beginning (T0) for both study groups, after 12 weeks (T3) for sample in therapy with biological drugs and after 24 weeks (T6) for sample in co-medication therapy. Results. The two-way ANOVA method was used to evaluate the standard deviations (SD): at T3 and T6 Group B obtained a significant PASI reduction and improvement of DLQI (✶ p value <0.05) compared to Group A. Conclusion. Our study shown that the patients treated with biologics in co-medication with topical therapy reached a significantly higher PASI and DQLI compared with those treated with only biologics. Furthermore we observed that the association with topical oinment showed more efficacy in the treatment of areas such as palm-plantar region, that is often difficult-to-treat region, even for biologic drugs. [ABSTRACT FROM AUTHOR]

An early identification of non-responders in oncology is of crucial importance to rapidly switch treatment regimens. Here we report a positron emission tomography, (PET)-guided switch from immunotherapy to targeted therapy in a patient affected by metastatic melanoma. We describe the case of a 78-years-old male patient diagnosed with nodular melanoma, submitted to baseline PET/CT with 18fluorodeoxyglucose (18F-FDG) that showed cutaneous and skeletal metastases (stage IV). The patients started immunotherapy with pembrolizumab. A PET/CT performed 3 months after the start of immunotherapy demonstrated progressive metabolic disease both at skeletal and cutaneous level, confirmed also by the biopsy. As patients resulted positive for BRAF V600k mutation, treatment regimen was rapidly switched to combined anti-BRAF/MEK targeted therapy. The PET/CT performed 3 months later, showed almost complete metabolic response. Ten months after the beginning of targeted therapy, the patient continues to present a durable metabolic response. PET/CT with 18F-FDG may help in monitoring the response to treatment in metastatic melanoma thus defining personalized therapeutic pathways. [ABSTRACT FROM AUTHOR]

Earth observation satellites are equipped with navigation components (star trackers, gyroscopes) which estimates the attitude of the satellite, corresponding to its orientation in the orbital reference frame. This equipment is essential for the localisation of the images which is done a posteriori and for the registration of the different images for a pushbroom sensor. This concerns both the registration of the spectral bands and the registration of multi-temporal series. However, the required accuracy is not always compatible with the performance of the attitude restitution. Moreover, some specific applications need more stringent geometric control even if requirements are met. With a multi-spectral pushbroom instrument, the same object on ground is seen as many times as number of spectral bands at different time instants: the attitude profile of the platform can be completely reconstructed from the results of the mapping of the different spectral bands. An attitude reconstruction method is proposed based on space triangulation inversion technique. The framework of this study is low-frequencies noise perturbations applied to Venμs satellite. Cubic splines are used for the attitude error profile, with 60 free parameters. Provided the physical model is representative, we show on two test cases that the convergence is very good. The band registration quality is used as a proxy to assess the performances. Residuals errors are less than 0.05 pixel for all tested band couples. [ABSTRACT FROM AUTHOR]

Background: Few studies have compared the efficacy of switching to adalimumab in the real‐life setting in plaque psoriasis patients. Objective: To evaluate the effect of adalimumab in psoriasis patients previously treated with other biologics. Methods: In this multicentre study, psoriasis patients (N = 262) treated with an anti‐TNF‐alpha agent, ustekinumab or naïve to biologics then switched to adalimumab were included. Disease severity was assessed by the Psoriasis Area and Severity Index (PASI) at baseline and after 3, 6, 12, 24 and 36 months. The association between clinical risk factors and achievement of PASI response was evaluated by logistic regression. Results: Adalimumab treatment resulted in a decrease in PASI (15.1 ± 6.2 at baseline vs. 2.7 ± 4.8 at 6 months, P < 0.0001), regardless of previous biologic treatment. Furthermore, adalimumab allowed 92.5%, 79% and 56% of patients to achieve PASI response (PASI 50, 75 and 90, respectively) and complete remission (PASI 100 response) in 48.4% of patients, by 6 months and maintained over 3 years, independent of prior biologic treatment. The absence of metabolic syndrome, dyslipidemia, hypertension and lower PASI and lower age at baseline was associated with achievement of PASI response at 3, 6 and 12 months, whereas at later time points (24 and 36 months), PASI 90 and PASI 100 response was associated with diagnosis of psoriasis/psoriatic arthritis. Conclusion: Adalimumab was effective at reducing PASI score over 3 years, irrespective of whether patients were biologic naïve or previously treated with a TNF‐alpha or IL‐12/23 inhibitor. [ABSTRACT FROM AUTHOR]

Abstract: Hidradenitis suppurativa (HS) is a chronic disorder of terminal follicular epithelium in the apocrine gland‐bearing areas. The long term therapy is based mainly on topical and/or systemic antibiotic use that could result in antibiotic resistance. The aim of our study was to present the real‐life experience based on the efficacy and tolerability of a novel lotion containing triethyl‐citrate, ethyl‐linoleate, and g‐peptide‐10 in the treatment of mild to moderate HS that has already shown effectiveness in acne treatment. This was an open‐label study on 30 patients of both sexes affected by HS. Patients were divided into two groups: 15 with Hurley I and 15 with Hurley II–III. The subjects were treated with the topical lotion, three‐times‐daily for eight weeks, with control at 4 (T1) and eight weeks (T2). Any other concomitant treatment (both topical and/or systemic) was avoided during study period. Improvement was observed in both Sartorius score grading system and inflammatory and noninflammatory lesion counts. The novel lotion has proved to be effective and well‐tolerated topical agent alone or in association with other topical and/or systemic tratments in HS, without side effects [ABSTRACT FROM AUTHOR]

On March 2020, COVID-19 has been declared as a pandemic emergency by World Health Organization (WHO). One paediatric patient had asthma (7%) and another patient had celiac disease and allergy. Twenty-three patients were adults with age ranging from 35 to 72 years, eight patients (35%) were male and 15 (65%) female, 12/23 (52%) had no previous disease. [Extracted from the article]

Background and Purpose The COX isoforms ( COX-1, COX-2) regulate human gut motility, although their role under pathological conditions remains unclear. This study examines the effects of COX inhibitors on excitatory motility in colonic tissue from patients with diverticular disease ( DD). Experimental Approach Longitudinal muscle preparations, from patients with DD or uncomplicated cancer (controls), were set up in organ baths and connected to isotonic transducers. Indomethacin ( COX-1/ COX-2 inhibitor), SC-560 ( COX-1 inhibitor) or DFU ( COX-2 inhibitor) were assayed on electrically evoked, neurogenic, cholinergic and tachykininergic contractions, or carbachol- and substance P ( SP)-induced myogenic contractions. Distribution and expression of COX isoforms in the neuromuscular compartment were assessed by RT-PCR, Western blot and immunohistochemical analysis. Key Results In control preparations, neurogenic cholinergic contractions were enhanced by COX inhibitors, whereas tachykininergic responses were blunted. Carbachol-evoked contractions were increased by indomethacin or SC-560, but not DFU, whereas all inhibitors reduced SP-induced motor responses. In preparations from DD patients, COX inhibitors did not affect electrically evoked cholinergic contractions. Both indomethacin and DFU, but not SC-560, decreased tachykininergic responses. COX inhibitors did not modify carbachol-evoked motor responses, whereas they counteracted SP-induced contractions. COX-1 expression was decreased in myenteric neurons, whereas COX-2 was enhanced in glial cells and smooth muscle. Conclusions and Implications In control colon, COX-1 and COX-2 down-regulate cholinergic motility, whereas both isoforms enhance tachykininergic motor activity. In the presence of DD, there is a loss of modulation by both COX isoforms on the cholinergic system, whereas COX-2 displays an enhanced facilitatory control on tachykininergic contractile activity. [ABSTRACT FROM AUTHOR]

β3-Adrenoceptor agonists protect against experimental gastric ulcers. We investigated the effects of the β3-adrenoceptor agonist SR58611A on 2,4-dinitrobenzene sulphonic acid-induced colitis in rats and analysed the expression of β3-adrenoceptors in the colonic wall. SR58611A was administered orally (1–10 mg kg−1) for 7 days, starting the day before induction of colitis. Colitis was assessed by macroscopic and histological scores, tissue myeloperoxidase activity, interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) levels. Reverse transcription-polymerase chain reaction and immunohistochemical analysis were used to examine the expression of β3-adrenoceptors. SR58611A significantly reduced the severity of colitis as well as the tissue levels of TNF-α, IL-1β and IL-6. Colitis was associated with a decreased expression of β3-adrenoceptor mRNA in the mucosal/submucosal layer of distal colon and this reduction was not affected by SR58611A. Immunohistochemical analysis revealed β3-adrenoceptors within the muscularis externa, in myenteric neurons and nerve fibres and in the submucosa. β3-Adrenoceptor immunoreactivity was decreased in inflamed tissues compared to controls, particularly in the myenteric plexus; this reduction was counteracted by SR58611A. Amelioration of experimental colitis by the selective β3-adrenoceptor agonist SR58611A suggests that β3-adrenoceptors may represent a therapeutic target in gut inflammation. [ABSTRACT FROM AUTHOR]

Emerging evidence indicates a nociceptive role of vagal afferents. A distinct oesophageal innervation in the rat, with muscular and mucosal afferents travelling predominantly in the recurrent (RLN) and superior laryngeal nerve (SLN), respectively, enabled characterization of mucosal afferents with nociceptive properties, using novel isolated oesophagus–nerve preparations. SLN and RLN single-fibre recordings identified 55 and 14 units, respectively, with none conducting faster than 8.7 m s−1. Mucosal response characteristics in the SLN distinguished mechanosensors ( n= 13), mechanosensors with heat sensitivity (18) from those with cold sensitivity (19) and a mechanoinsensitive group (5). The mechanosensitive fibres, all slowly adapting, showed a unimodal distribution of mechanical thresholds (1.4–128 mN, peak ∼5.7 mN). No difference in response characteristics of C and Aδ fibres was encountered. Mucosal proton stimulation (pH 5.4 for 3 min), mimicking gastro-oesophageal reflux disease (GORD), revealed in 31% of units a desensitizing response that peaked around 20 s and faded within 60 s. Cold stimulation (15°C) was proportionally encoded but the response showed slow adaptation. In contrast, the noxious heat (48°C) response showed no obvious adaptation with discharge rates reflecting the temperature's time course. Polymodal (69%) mucosal units, > 30% proton sensitive, were found in each fibre category and were considered nociceptors; they are tentatively attributed to vagal nerve endings type I, IV and V, previously morphologically described. All receptive fields were mapped and the distribution indicates that the posterior upper oesophagus may serve as a ‘cutbank’, detecting noxious matters, ingested or regurgitated, and triggering nocifensive reflexes such as bronchoconstriction in GORD. [ABSTRACT FROM AUTHOR]

Prostaglandins regulate various functions throughout the gastrointestinal system. Their biosynthesis depends on cyclooxygenase isoforms, named COX-1 and COX-2. The initial hypothesis that COX-2 is an inducible enzyme has been challenged and its constitutive expression in the stomach has been established. In this study, an immunohistochemical analysis was performed to evaluate the distribution and cellular localization of COX-2 in normal human colon. Colonic surgical specimens were processed for COX-2, protein HuC/HuD, neurofilament, S-100 protein and CD117/c-kit immunodetection. COX-2 protein was found to be constitutively expressed in the colonic wall: detectable amounts were localized in mucosal, submucosal and muscular layers, mainly in the neuromuscular compartment. In particular, COX-2 was expressed in muscularis mucosae, submucosal ganglia, longitudinal muscle layer and myenteric ganglia, the neurons of which displayed different degrees of immunostaining. Intramuscular interstitial cells of Cajal, regarded as important sites for the regulation of enteric neuromuscular activity, were also partly COX-2 immunoreactive. This study provides a detailed mapping of COX-2 expression in human colon, and allows better understanding of the roles played by this isoenzyme in gut physiology. [ABSTRACT FROM AUTHOR]

In mouse the cannabinoid receptor 2 (CB2) agonists L768242 and (+)-AM1241, at doses of 30 mg/kg i.p. and 1 and 3 mg/kg i.v., respectively, reduced the second phase of nocifensive behaviors elicited by formalin intraplantar injection. This effect was counteracted by the selective CB2 antagonist SR144528 (1 mg/kg i.p.). In rat (+)-AM1241 (3 and 6 mg/kg i.v.) and L768242 (30 mg/kg i.p.) reduced allodynia elicited by L5–L6 spinal nerve ligation. SR144528 reverted these effects, supporting a CB2-mediated action. To clarify the mechanisms underlying these effects we investigated CB2 gene expression and function in the nervous system. CB2 mRNA was expressed in spinal cord and dorsal root ganglia (DRG) of both sham and neuropathic rats and was up-regulated in the ipsilateral spinal cord of neuropathic rats. Expression studies demonstrated the presence of CB2 mRNA in culture of spinal cord microglia. A biomarker, CGRP, was used to investigate modulation of DRG primary afferents by CB2 agonists. Both L768242 and (+)-AM1241 dose dependently (EC50 of 3.6 and 4.5 nm, respectively) reduced capsaicin-induced calcitonin gene-related peptide (CGRP) release. Coadministration of SR144528 resulted in a rightforward shift (pKB 8.1 and 8.2 for (+)-AM1241 and L768242, respectively) of the dose–response curve. Experiments on capsaicin-induced CGRP release in tissue from CB1–/– mice ruled out a CB1-mediated effect. These results confirm that CB2 is present in the central nervous system and suggest that CB2 agonists may elicit their analgesic effect by acting not only at non-neuronal peripheral sites but also at neural level, making CB2 an attractive target for chronic pain treatment. [ABSTRACT FROM AUTHOR]

The new combination between the nucleoside analogue gemcitabine and the cholesterol-lowering drug fluvastatin was investigated in vitro and in vivo on the human pancreatic tumour cell line MIAPaCa-2. The present study demonstrates that fluvastatin inhibits proliferation, induces apoptosis in pancreatic cancer cells harbouring a p21ras mutation at codon 12 and synergistically potentiates the cytotoxic effect of gemcitabine. The pharmacologic activities of fluvastatin are prevented by administration of mevalonic acid, suggesting that the shown inhibition of geranyl-geranylation and farnesylation of cellular proteins, including p21rhoA and p21ras, plays a major role in its anticancer effect. Fluvastatin treatment also indirectly inhibits the phosphorylation of p42ERK2/mitogen-activated protein kinase, the cellular effector of ras and other signal transduction peptides. Moreover, fluvastatin administration significantly increases the expression of the deoxycytidine kinase, the enzyme required for the activation of gemcitabine, and simultaneously reduces the 5'-nucleotidase, responsible for deactivation of gemcitabine, suggesting a possible additional role of these enzymes in the enhanced cytotoxic activity of gemcitabine. Finally, a significant in vivo antitumour effect on MIAPaCa-2 xenografts was observed with the simultaneous combination of fluvastatin and gemcitabine, resulting in an almost complete suppression and a marked delay in relapse of tumour growth. In conclusion, the combination of fluvastatin and gemcitabine is an effective cytotoxic, proapoptotic treatment in vitro and in vivo against MIAPaCa-2 cells by a mechanism of action mediated, at least in part, by the inhibition of p21ras and rhoA prenylation. The obtained experimental findings might constitute the basis for a novel translational research in humans. [ABSTRACT FROM AUTHOR]

The small G protein Rho subfamily controls several cellular events such as growth, movement, proliferation and differentiation by rearranging actin and cytoskeleton proteins. Most of these effects are mediated by the activation of growth factor and extracellular matrix molecule receptors, suggesting a role for Rho molecules in the transduction pathway of these receptors. Despite the importance of Rho peptides in fundamental cellular events, data on their subcellular immunolocalisation are sparse: here we investigated the expression and subcellular localisation of RhoA in resting (cultured on plastic) and activated (Matri-cell or hepatocyte growth factor) MDCK cells by immunoperoxidase and immunogold techniques. Resting MDCK cells contain detectable amounts of RhoA mainly localised in the cytoplasm; RhoA expression is significantly enhanced by Matri-cell substrates that promote translocation of RhoA at the membrane level. This enhancing effect is reduced after exposure to hepatocyte growth factor. [ABSTRACT FROM AUTHOR]

Laminin, an extracellular matrix molecule (EMM) widely expressed in the basal laminae, interacts with specific membrane receptors among which the integrin molecules are the best known. During embryo development laminin is the first synthesized EMM and plays a significant role in the morphogenesis of organs in which epithelial-mesenchymal interactions and branching take place. The present study describes the distribution of laminin and of β1 integrin receptors during the very early stages of human kidney development. The observations were carried out on paraffin sections of human embryos ranging between the 4th and the 7th gestational week. Laminin was detected within the basement membranes of mesonephric duct, vesicles, glomerular vessels and celomic epithelium. The metanephric anlage reacted with anti-laminin immunoglobulins in the basement membrane underlying the ampullae and in few blastemic cap cells. Low levels of β1 integrin reactivity were found in both the mesonephric and metanephric structures. This study provides for the first time data about the distribution of laminin and β1 integrin in the early stages of human renal organogenesis suggesting a key role for these molecules in the epithelial-mesenchymal interactions necessary for kidney development. [ABSTRACT FROM AUTHOR]

The skin penetration of roxithromycin was studied in 27 surgical patients treated with 300 mg orally followed by three oral doses of 150 mg 12-hourly. Peak plasma and skin concentrations of 7.9±1.2 mg/l and 31.3±3.7 mg/kg occurred 2.5 and 4 h after last dosing respectively. The plasma and skin half-lives were 7.7 and 6.0 h, and the mean plasma and skin area under the curve values were 64.3 mg/l.h and 155.3 mg/kg.h. Skin/plasma concentration ratios were 4.9±0.5, 9.7±1.2, 7.6±0.8 and 5.9±1.1, at 3, 4, 5 and 6 h after last dosing respectively. These results demonstrate that roxithromycin achieves high levels in human skin. [ABSTRACT FROM PUBLISHER]

The purpose of this study was to evaluate the optimal timing of ADR-529 administration to protect rats treated with doxorubicin (DXR) against drug-induced cardiotoxicity. Complete electrocardiographic monitoring (QRS complex, S alpha T segment and T wave) and the histopathological analysis of cardiac tissue were used to assess the degree of heart damage produced in female rats treated with ten i.v. doses of 1 mg/kg DXR over a period of 15 weeks; body-weight increase and survival were also analyzed to evaluate the toxicity of treatments. Cardiac alterations induced by DXR were compared with those occurring in animals receiving 20 mg/kg i.v. ADR-529 at 30 min prior to DXR administration, starting at the first, third, or sixth DXR dose and given until the end of the study (15th week). Rats treated with DXR were severely cardiomyopathic, showing progressive and irreversible ECG alterations (QRS-complex and S alpha T-segment widening and T-wave flattening) and marked degeneration of the myocardium (myocyte vacuolation, myofibrillar loss, and endomyocardial fibrosis). The most effective cardiac protection was provided by the administration of ADR-529 beginning with the first or third DXR dose. Delaying treatment with ADR-529 until the sixth DXR dose resulted in a significant reduction in its therapeutic action on heart damage. A significant difference in body-weight increase and survival was observed between the treatment groups: ADR-529 injected prior to the first DXR dose significantly protected animals from DXR toxicity, but this schedule was significantly more toxic than the administration of ADR-529 beginning with the third or sixth DXR dose. Taking into account the degree of cardiac protection and the toxicity of combination treatments, the results of the present study demonstrate the superiority of ADR-529 given prior to the third DXR dose over the other schedules tested. This finding suggests that significant protection against DXR-induced chronic cardiotoxicity in the rat can be obtained using deferred treatment with ADR-529. [ABSTRACT FROM AUTHOR]

The acute and chronic cardiotoxicity and cytotoxicity of the novel doxorubicin (DXR) derivative 4'-amino-3'-hydroxy-DXR were compared with those of 4'-deoxy-DXR and DXR. In the acute cardiotoxicity study, the ECG and hemodynamic changes recorded in anesthetized rats that had been treated i.v. with 10 mg/kg 4'-amino-3'-hydroxy-DXR or 8.6 mg/kg 4'-deoxy-DXR were significantly less severe than those caused by 13 mg/kg DXR. In the chronic cardiotoxicity study, rats received 3 weekly i.v. injections of 3 mg/kg DXR, 3 mg/kg 4'-amino-3'-hydroxy-DXR, or 2 mg/kg 4'-deoxy-DXR during the first 14 days of the study and were observed for an additional 35-day period. DXR induced severe cardiomyopathy that was characterized by ECG changes in vivo (S alpha T-segment widening and T-wave flattening) and by impairment of the contractile responses (Fmax, +/- dF/dtmax) to adrenaline of hearts isolated from treated animals. 4'-Deoxy-DXR caused a progressive enlargement of the S alpha T segment in vivo and a significant impairment of the -dF/dtmax value in vitro, which were less severe than those produced by DXR. The least cardiotoxic drug was 4'-amino-3'-hydroxy-DXR, which induced minor ECG changes without causing significant alterations in the contractile responses of isolated hearts to adrenaline. On the basis of the drug concentration required to inhibit 50% of the colony formation (IC50) of cell lines in vitro, 4'-amino-3'-hydroxy-DXR was less active than 4'-deoxy-DXR but at least twice as active as DXR against human cancer and murine transformed cell lines. These data indicate that 4'-amino-3'-hydroxy-DXR is significantly less cardiotoxic and more cytotoxic than DXR. [ABSTRACT FROM AUTHOR]

The acute and chronic cardiotoxicity as well as the cytotoxicity of 4'-deoxy-4'-iodo-doxorubicinol (I-DXRol), the major metabolite of the doxorubicin (DXR) derivative 4'-deoxy-4'-iodo-DXR (I-DXR), were compared with those of I-DXR and DXR. In the acute study, anesthetized rats received i.v. DXR (10 mg/kg), I-DXR (4 mg/kg), or I-DXRol (4 mg/kg) and were monitored for ECG (S alpha T segment and T wave), systolic (SBP) and diastolic (DBP) blood pressure, the first derivative of the systemic arterial pressure (SA dP/dtmax), and heart rate. Treatments induced a significant widening of the S alpha T segment, but I-DXRol was significantly less toxic than I-DXR or DXR. As compared with control values, DXR induced a marked increase in SBP and DBP and a decrease in SA dP/dtmax, whereas I-DXR and I-DXRol induced modest changes in hemodynamic parameters. In the chronic study, 3 mg/kg DXR given to rats by i.v. bolus once a week for 3 weeks resulted in severe chronic cardiotoxicity that lasted 6 weeks and was characterized by S alpha T-segment widening, T-wave flattening, and severe cardiac histological damage. Doses of 1.2 mg/kg I-DXR and 1.2 and 2.4 mg/kg I-DXRol, given i.v. once a week for 3 weeks, and 3.6 mg/kg I-DXRol given as a single dose were associated with a significant T-wave voltage reduction; I-DXR and 2.4 mg/kg I-DXRol induced significant histological alterations of cardiac tissue as compared with control values, whereas modest alterations of heart tissue were observed after injections of 1.2 and 3.6 mg/kg I-DXRol in three doses and in a single dose, respectively. The cytotoxicity of the three anthracyclines against one glioblastoma cell line and two human small-cell lung cancer lines was similar. Results indicate that the acute cardiotoxicity of I-DXRol is lower than that of I-DXR and DXR, whereas the chronic heart damage is similar to that induced by I-DXR and significantly lower compared than that caused by DXR. Moreover, the cytotoxicity of the metabolite appears to be similar to that of I-DXR and DXR. The lack of additional cardiac toxicity due to I-DXRol further supports the lower overall cardiac toxicity of I-DXR, which retains a cytotoxic activity similar to that of the parent drug. [ABSTRACT FROM AUTHOR]

The effects of fructose-1,6-diphosphate, an intermediate metabolite of glycolysis, on acute and chronic cardiotoxicity of doxorubicin were investigated in rats. In the acute study, urethane-anaesthetized Wistar female rats treated with 10 mg/kg i.v. doxorubicin developed a widening of the S alpha T segment, an impairment of +dP/dtmax, and tachycardia. Pretreatment with 375 and 750 mg/kg i.p. fructose-1,6-diphosphate prevented the S alpha T segment from widening, whereas only 750 mg/kg i.p. significantly attenuated the heart rate increase. Chronic cardiomyopathy was induced over a 6-week period by weekly doses of 3 mg/kg i.v. doxorubicin, being characterized in vivo by the progressive enlargement of the S alpha T segment and the occurrence of histological alterations and in vitro by a marked impairment of the inotropic response elicited by adrenaline in isolated hearts from treated rats. Concurrent treatment with 150 and 300 mg/kg i.p. fructose-1,6-diphosphate thrice a week for 6 weeks did not lessen the chronic heart damage, whereas 600 mg/kg given i.p. significantly reduced the widening of the S alpha T segment and the severity of histological damage in vivo, as well as significantly improving the contractile responses of hearts in vitro. These findings suggest that the administration of fructose-1,6-diphosphate plays a protective role in the acute and chronic cardiotoxicity of doxorubicin in the rat. [ABSTRACT FROM AUTHOR]

The presence of a multidrug resistance (MDR) related protein, P-170, in normal and pathological lymphoid cells has been described. The present report evaluates the expression of the mdr 1 gene by using the reverse Polymerase Chain Reaction (PCR) on cells obtained from the thymus and bursa of chicken embryos starting from day 12 until hatching. Results show that the thymic cells are positive from day 12 to the end of the observation period. In contrast, mdr mRNA was detected in the bursa from day 14 to day 17 of embryonic life. Possible relationships between the expression of mdr and the development of T and B lymphocytes are discussed. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a chronic relapsing disorder of the apocrine gland affecting mainly areas subjected to friction (e.g. the axillae, groin, perineum and medial aspects of the thighs). This condition can be linked to different comorbidities: autoimmune and inflammatory disease, hormone‐related disorders, obesity and the metabolic syndrome, as well as rare syndromes such as Bazex–Dupré–Christol, Down's, KID, PAPASH, PASS, PASH, and SAPHO syndromes, or Dowling–Degos disease. We report a case of severe HS in a patient with Trisomy 1q;13, a very rare cytogenetic anomaly characterized by severe anomalies including dysmorphisms, multiple congenital malformations, heart defects and intellectual disability. [ABSTRACT FROM AUTHOR]

Doxorubicin (DXR) (0.17×10) induces an acute cardiotoxicity in isolated rat heart; there is a progressive widening of the SαT segment, with a decrease in force derivatives and in the coronary flow. Concurrent perfusion with fructose-1,6-diphosphate (FDP) (10-10) dose-dependently reduces the SαT enlargement but fails to affect the reduction in force derivatives and coronary flow. The target of cardiac protection by FDP might be the ionic mechanisms underlying the action potential configuration. [ABSTRACT FROM AUTHOR]

Real-time/performed electroacoustic music is currently facing a serious sustainability problem. Although historically its production is very recent, several technological revolutions have gone by in the meantime. Most of these works can hardly be performed because the technology involved has gone lost since the first realization, and no long-standing notational precaution was ever taken. This paper (first published in 2005 and translated in Italian for the first time) presents some typical case studies and introduces some techniques that might lead to a partial -- when not completely adequate -- solution to the sustainability problem. [ABSTRACT FROM AUTHOR]

Background Symptoms of digestive dysfunction in patients with Parkinson's disease ( PD) occur at all stages of the disease, often preceding the onset of central motor symptoms. On the basis of these PD-preceding symptoms it has been proposed that PD could initiate in the gut, and that the presence of alpha-synuclein aggregates, or Lewy bodies in the enteric nervous system might represent one of the earliest signs of the disease. Following this hypothesis, much research has been focused on the digestive tract to unravel the mechanisms underlying the onset and progression of PD, with particular attention to the role of alterations in enteric neurotransmission in the pathophysiology of intestinal motility disturbances. There is also evidence suggesting that the development of central nigrostriatal neurodegeneration is associated with the occurrence of gut inflammation, characterized by increments of tissue pro-inflammatory markers and oxidative stress, which might support conditions of bowel neuromotor abnormalities. Purpose The present review intends to provide an integrated and critical appraisal of the available knowledge on the alterations of enteric neuromuscular pathways regulating gut motor activity both in humans and preclinical models of PD. Moreover, we will discuss the possible involvement of neuro-immune mechanisms in the pathophysiology of aberrant gastrointestinal gut transit and neuromuscular activity in the small and large bowel. [ABSTRACT FROM AUTHOR]