Efficacy and Tolerability of a New Formulation in Rectal Ointment Based on Zn-L-Carnosine (Proctilor®) in the Treatment of Haemorrhoidal Disease

Haemorrhoidal disease (HD) shows high prevalence in western countries, reaching 4.4% per year in the US. Topical preparations are the first-line treatments, which are readily available as "over-the-counter" (OTC) products, often containing a nonstandardised mixture of "natural" remedies, or anaesthetics or cortisol;those latter are not free from undesirable effects. The Zinc-L-Carnosine is a cytoprotective compound, promoting mucosal repair in the gastrointestinal tract and also in mucosal repair, following radiation injuries to the rectum as well as in ulcerative colitis. Our aim was to study the efficacy of Zinc-L-Carnosine in relieving acute symptoms of HD, testing a preparation in the rectal ointment, Proctilor (R), in patients complaining of bleeding or thrombosed piles. In a multicentre open trial, 21 patients older than 18 years of age were enrolled. The symptoms of HD were graded according to the Haemorrhoidal Disease Symptoms Score (HDSS) in association with the Short Health Scale (SHS) to assess the influence of HD on quality of life. The pain was assessed with the VAS score, bowel habit by means of the Bristol scale. The patients were evaluated at enrolment (T0) and 2 (T1) and 4 (T2) weeks of treatment with Proctilor (R) rectal ointment. There were 10 men and 11 women; mean age, 49 years. Pain, bleeding, and thrombosis were all significantly reduced after treatment; the mean VAS score decreased from 4.71 +/- 3.05 at T0 to.52 +/- 0.87 and.05 +/- 0.22 at T1 and T2, respectively; (mean +/- SD; p < 0.001 in both cases). Similarly, the HDSS score showed to be significantly reduced between T0, T1 (8.05 +/- 4.55 vs. 1.14 +/- 1.01), and T2 (8.05 +/- 4.55 vs. 24 +/- 0.44) (mean +/- SD; p < 0.001 in both cases). Quality of life showed to be improved as the SHS score decreased significantly with treatment (7.90 +/- 4.17 at T0 vs. 4.24 +/- 0.44 at T1 vs. 4.05 +/- 0.22 at T2; mean +/- SD; p < 0.001 in both cases). The Bristol score of defecation remained substantially unchanged. No side effects or discontinuation of treatment were reported. Results of our investigation suggest a role of Proctilor (R) rectal ointment in treating symptomatic HD with good results and an excellent safety profile. However, our preliminary results encourage further studies on a larger number of patients to confirm the role of Zinc-L-Carnosine in the rectal ointment for the topical treatment of HD

Action of combined magnetic fields on aqueous solution of glutamic acid: the further development of investigations

In the present work the results of the known investigation of the influence of combined static (40 μT) and alternating (amplitude of 40 nT) parallel magnetic fields on the current through the aqueous solution of glutamic acid, were successfully replicated. Fourteen experiments were carried out by the application of the combined magnetic fields to the solution placed into a Plexiglas reaction vessel at application of static voltage to golden electrodes placed into the solution. Six experiments were carried out by the application of the combined magnetic fields to the solution placed in a Plexiglas reaction vessel, without electrodes, within an electric field, generated by means of a capacitor at the voltage of 27 mV. The frequency of the alternating field was scanned within the bounds of 1.0 Hz including the cyclotron frequency corresponding to a glutamic acid ion and to the applied static magnetic field. In this study the prominent peaks with half-width of ~0.5 Hz and with different heights (till 80 nA) were registered at the alternating magnetic field frequency equal to the cyclotron frequency (4.2 Hz). The general reproducibility of the investigated effects was 70% among the all solutions studied by us and they arose usually after 40–60 min. after preparation of the solution. In some made-up solutions the appearance of instability in the registered current was noted in 30–45 min after the solution preparation. This instability endured for 20–40 min. At the end of such instability period the effects of combined fields action appeared practically every time. The possible mechanisms of revealed effects were discussed on the basis of modern quantum electrodynamics

Well-Being and Perceived Quality of Life in Elderly People Displaced After the Earthquake in L’Aquila, Italy

On 6 April 2009, the city of L’Aquila was hit by a violent earthquake that destroyed almost all of its medieval centre, and the surviving inhabitants were evacuated and relocated in temporary quarters or undamaged homes. The aim of this study was to investigate the perceived quality of life of the elderly population 3 years after the earthquake in relation to the social and logistic issues of new housing. The study was carried out between October 2011 and March 2012, and involved 571 subjects aged over 65 years living in the municipality of L’Aquila. The interviews took place in the surgeries of general practitioners and the city’s Department of Prevention and Vaccination in the anti-influenza immunisation period. The instrument used was a 36-item questionnaire with closed, multiple choice answers divided into the following sections: demographics, everyday activities, health and perceived health, and the quality of life in the city. The results show that, 3 years after the earthquake, the elderly population living in the new towns and temporary housing of L’Aquila have a worse perception of their quality of life than the others. They feel a certain social isolation and wish to live elsewhere. Governments faced with the problems arising from a natural calamity should take into account all of the elements making up a good quality of life and, before making choices whose impact cannot be changed, consider both their immediate and long-term social consequences

Modulation of tumor angiogenesis by conditional expression of fibroblast growth factor-2 affects early but not established tumors.

Fibroblast growth factor-2 (FGF2) is a pleiotropic heparin-binding growth factor endowed with a potent angiogenic activity in vitro and in vivo. To investigate the impact of the modulation of FGF2 expression on the neovascularization at different stages of tumor growth, we generated stable transfectants (Tet-FGF2) from the human endometrial adenocarcinoma HEC-1-B cell line in which FGF2 expression is under the control of the tetracycline-responsive promoter (Tet-off system). After transfection, independent clones were obtained in which FGF2 mRNA and protein were up-regulated compared with parental cells. Also, the conditioned medium of Tet-FGF2 transfectants caused proliferation, urokinase-type plasminogen activator up-regulation, migration, and sprouting of cultured endothelial cells. A 3-day treatment of Tet-FGF2 cell cultures with tetracycline abolished FGF2 overexpression and the biological activity of the conditioned medium without affecting their proliferative capacity. Tet-FGF2 cells formed tumors when nude mice received s.c. injections. The administration of 2.0 mg/ml tetracycline in the drinking water before cell transplantation, continued throughout the whole experiment, inhibited FGF2 expression in Tet-FGF2 tumor lesions. This was paralleled by a significant decrease in the rate of tumor growth and vascularization to values similar to those observed in lesions generated by parental HEC-1-B cells. Tetracycline administration 20 days after tumor cell implant, although equally effective in reducing FGF2 expression and inhibiting tumor vascularity, only minimally impaired the growth of established Tet-FGF2 tumors. The results indicate that FGF2 expression deeply affects the initial tumor growth and neovascularization of HEC-1-B human endometrial adenocarcinoma in nude mice. On the contrary, the growth of established tumors appears to be independent of the inhibition of FGF2 expression and decreased vascular density. The possibility that a significant reduction of angiogenesis may not affect the progression of large tumors points to the use of antiangiogenic therapy in early tumor stage

The use of Lausanne Trilogue Play in three cases of gastroschisis diagnosed during pregnancy

From pregnancy to the 1st years of a child\u2019s life, families develop and increase representations and interactive competences toward the child. Prenatal diagnosis of a severe fetus\u2019 defect could profoundly alter the parental perception and development of these representations. The aim of the study was to evaluate triadic interactions in families, whose baby was prenatally diagnosed with severe gastroschisis. Three families took part in the preliminary case study, which was carried out when the babies were 6 months old. The Lausanne Trilogue Play shows that prenatal diagnosis of fetal malformation may affect family triadic interactions as follows: (a) parents, especially mothers, tend to be intrusive during the play; (b) parents presents maladjustments in the child stimulations, especially during the third part, when both parents have to simultaneously interact with the baby; (c) parents experience difficulties in creating a space that allows them to communicate directly with each other, leaving the child in a peripheral position. Observational data and clinical implications are discussed

A single dose of allopregnanolone affects rat ovarian morphology and steroidogenesis

Allopregnanolone, a progesterone metabolite, is one of the best characterized neurosteroids. In a dose that mimics serum levels during stress, allopregnanolone inhibits sexual receptivity and ovulation and induces a decrease in luteinizing hormone levels. The aim of this work was to examine the effect of an intracerebroventricular administration of allopregnanolone on ovarian morphophysiology; serum and tissue levels of progesterone and estrogen; and enzymatic activity of 3β-hydroxysteroid dehydrogenase, 20α-hydroxysteroid dehydrogenase and 3α-hydroxysteroid oxido-reductase in the ovary and in the medial basal hypothalamus on the morning of estrus. Ovarian morphology was analyzed under light microscopy. The hormone assays were performed by radioimmunoassay. The enzymatic activities were measured by spectrophotometric analysis. The morphometric analysis revealed that, in allopregnanolone-treated animals, the number of secondary and Graafian follicles was decreased, whereas that of atretic follicles and cysts was significantly increased. Some cysts showed luteinized unruptured follicles. There were no differences in the number of tertiary follicles or corpora lutea in comparison with the corresponding control groups. In allopregnanolone-treated animals, progesterone serum levels were increased, whereas ovarian progesterone levels were decreased. Moreover, 3β-HSD and 3α-HSOR enzymatic activities were increased in the medial basal hypothalamus, whereas ovarian levels were decreased. The enzyme 20α-hydroxysteroid dehydrogenase showed the opposite profile. The results of this study showed that allopregnanolone interferes on ovarian steroidogenesis and ovarian morphophysiology in rats, providing a clear evidence for the role of this neurosteroid in the control of reproductive function under stress situations.Fil: Pelegrina, Laura Tatiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Cáceres Gimenez, Antonella Rosario Ramona. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Giuliani, Fernando Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Asensio, Joana Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Parborell, Maria Fernanda Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Laconi, Myriam Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

CD38 and bone marrow microenvironment.

This review summarizes the events ruled by CD38 shaping the bone marrow environment, recapitulating old and new aspects derived from the body of knowledge on the molecule. The disease models considered were myeloma and chronic lymphocytic leukemia (CLL). CD38 has been analyzed considering its twin function as receptor and enzyme, roles usually not considered in clinics, where it is used as a routine marker. Another aspect pertaining basic science concerns the role of the molecule as a member of an ectoenzyme network, potentially metabolizing soluble factors not yet analyzed (e.g., NAD+, ATP, NAM) or influencing hormone secretion (e.g., oxytocin). The last point is focused on the use of CD38 as a target of an antibody-mediated therapeutic approach in myeloma and CLL. A recent observation is that CD38 may run an escape circuit leading to the production of adenosine. The generation of local anergy may be blocked by using anti-CD38 antibodies. Consequently, not only might CD38 be a prime target for mAb-mediated therapy, but its functional block may contribute to general improvement in cancer immunotherapy and outcomes

Imported Loa Loa Filariasis: Three Cases and a Review of Cases Reported in Non-Endemic Countries in the Past 25 Years

Summary Objectives The aim of this study was to highlight the increasing chance of Western physicians encountering patients (both immigrants and expatriates/travelers) seeking help for loiasis. Methods We describe three cases of imported loiasis observed at two hospitals in Italy and France, and present a review of all previously published cases in the medical literature in the last 25 years (1986–2011). The search was performed using PubMed and Scopus databases using the terms " Loa loa " AND "loiasis". Results We reviewed 101 cases of imported loiasis of which 61 (60.4%) were reported from Europe and 31 (30.7%) from the USA. Seventy-five percent of infestations were acquired in three countries: Cameroon, Nigeria, and Gabon. Overall, peripheral blood microfilariae were detected in 61.4% of patients, eosinophilia in 82.1%, eye worm migration in 53.5%, and Calabar swellings in 41.6%. However, Calabar swellings and eosinophilia were more common among expatriates/travelers, whereas African immigrants were more likely to have microfilaremia. Eye worm migration was observed in a similar proportion in the two groups. Only 35 patients (including the three described here) underwent clinical follow-up for a median period of 10.5 months (range 1–84 months); clinical relapse occurred in three of these patients and persistence or reappearance of blood microfilaria in another two. Conclusions Due to increasing travel and the migration of people from the endemic countries of West Africa to Europe and the USA, we speculate on the possible emergence of loiasis. Western physicians should be aware of the typical (eye worm migration and Calabar swellings) as well as unusual clinical presentations

Un lampo obliquo. Luigi Bernardi, i suoi libri e il suo immaginario

In occasione del decennale della morte di Luigi Bernardi (Ozzano dell’Emilia, 1953 - Bologna, 2013), il volume - a cura di Filippo Milani e Alberto Sebastiani - raccoglie gli atti relativi all’evento di inaugurazione del Fondo “Luigi Bernardi”, che si è svolto il 17 gennaio 2020 presso gli spazi del Dipartimento di Filologia classica e Italianistica dell’Università di Bologna, poche settimane prima che la pandemia sconvolgesse le vite di tutte e tutti noi. Si è trattato della prima iniziativa volta a valorizzare il Fondo archivistico e librario dello scrittore emiliano, che merita di certo ulteriori studi e approfondimenti, volti a indagare sia l’attività creativa di Bernardi sia quella di editore, traduttore, promotore culturale e scopritore di talenti letterari e fumettistici, soprattutto nell’ambito del genere noir. In quell’occasione era stata allestita anche una mostra virtuale - tuttora accessibile - che offre una prima visione panoramica sugli interessi dell’autore e sulla composizione della sua biblioteca

The role of stakeholder involvement in the evolving EU HTA process:Insights generated through the European Access Academy’s multi-stakeholder pre-convention questionnaire

Involvement of all relevant stakeholders will be of utmost importance for the success of the developing EU HTA harmonization process. A multi-step procedure was applied to develop a survey across stakeholders/collaborators within the EU HTA framework to assess their current level of involvement, determine their suggested future role, identify challenges to contribution, and highlight efficient ways to fulfilling their role. The ‘key’ stakeholder groups identified and covered by this research included: patients‘, clinicians‘, regulatory, and Health Technology Developer representatives. The survey was circulated to a wide expert audience including all relevant stakeholder groups in order to determine self-perception by the ‘key’ stakeholders regarding involvement in the HTA process (self-rating), and in a second, slightly modified version of the questionnaire, to determine the perception of ‘key’ stakeholder involvement by HTA bodies, payers, and policymakers (external rating). Predefined analyses were conducted on the submitted responses. Fifty-four responses were received (patients 9; clinicians: 8; regulators: 4; HTDs 14; HTA bodies: 7; Payers: 5; policymakers 3; others 4). The mean self-perceived involvement score was consistently lower for each of the ‘key’ stakeholder groups than the respective external ratings. Based on the qualitative insights generated in the survey, a RACI Chart (Responsible/Accountable/Consulted/Informed) was developed for each of the stakeholder groups to determine their roles and involvement in the current EU HTA process. Our findings suggest extensive effort and a distinct research agenda are required to ensure adequate involvement of the key stakeholder groups in the evolving EU HTA process.</p