A multicentre, open-label, single-arm phase II trial of the efficacy and safety of sclerotherapy using 3% polidocanol foam to treat second-degree haemorrhoids (SCLEROFOAM).

BACKGROUND: The aim of the present study was to evaluate the efficacy and safety of 3% polidocanol foam for treating 2nd-degree haemorrhoids. METHODS: A multicentre, open-label, single-arm, phase 2 trial involving 10 tertiary referral centres for haemorrhodal disease (HD) was performed. Between January and June 2019, patients with 2nd-degree haemorrhoids were prospectively included in this study. The primary outcome was to establish the success rate after one sclerotherapy session in terms of complete resolution of bleeding episodes one week after the injection. The Hemorrhoidal Disease Symptom Score (HDSS), the Short Health Scale for HD (SHS-HD) score and the Vaizey incontinence score were used to assess symptoms and their impact on quality of life and continence. Pain after the procedure, subjective symptoms and the amount and type of painkillers used were recorded. Patients were followed up for 1 year. RESULTS: There were 183 patients [111 males; 60.7%, mean age 51.3 ± 13.5 (18-75) years]. Complete resolution of bleeding was reached in 125/183 patients (68.3%) at 1 week and the recurrence rate was 12% (15/125). Thirteen patients (7.4%) underwent a second sclerotherapy session, while only 1 patient (1.8%) had to undergo a third session. The overall 1-year success rate was 95.6% (175/183). The HDSS and the SHS score significantly improved from a median preoperative value of 11 and 18 to 0 and 0, respectively (p < 0.001). There were 3 episodes of external thrombosis. No serious adverse events occurred. CONCLUSIONS: Sclerotherapy with 3% polidocanol foam is a safe, effective, painless, repeatable and low-cost procedure in patients with bleeding haemorrhoids.

Multiple electron capture from isolated protein poly-anions in collision with slow highly charged ions.

Collisions of 375 keV Xe25+ ions with trapped mass/charge selected poly-anions of the cytochrome C protein (∼12.5 kDa) were studied by coupling a linear quadrupole ion trap with low-energy ion beam facility. Tandem mass spectra were recorded for the protein precursor charge states ranging from -9 to -17. The present work reports the first study of slow highly charged ion collisions with poly-anions. A high signal to noise ratio allowed the study of the intensity of single and multiple electron removal by a projectile, as well as associated neutral losses, as a function of the target charge state. Relative single and double electron detachment cross sections were found to increase with increasing charge state of the precursor anion. The experimental findings are supported by the calculations of the total electron capture cross sections, based on the classical over-the-barrier model, restricted to a simple uniformly charged linear protein structure and a near-end electron capture.

Osteogenic potential of dualblocks cultured with human periodontal ligament stem cells: in vitro and synchrotron microtomography study.

BACKGROUND AND OBJECTIVE: In the present study, the early stages of in vitro bone formation in collagenated porcine scaffolds cultured with human periodontal ligament cells were investigated. The comparison between the osteogenic potential of this structure in basal and differentiating culture media was explored to predict the mechanism of its biological behavior as graft in human defect. Results were validated by synchrotron radiation X-Ray phase contrast computed microtomography (micro-CT). As the periodontal disease plays a key role in systemic and oral diseases, it is crucial to find advanced therapeutic clinical interventions to repair periodontal defects. This has been recently explored using cells and tissues developed in vitro that should ideally be immunologically, functionally, structurally and mechanically identical to the native tissue. MATERIAL AND METHODS: In vitro cultures of human periodontal ligament cells, easily obtained by scraping of alveolar crestal and horizontal fibers of the periodontal ligament, were seeded on to collagenated porcine blocks constituted by natural cancellous and cortical bone. 3D images were obtained by synchrotron radiation micro-CT and processed with a phase-retrieval algorithm based on the transport of intensity equation. RESULTS: Starting from the second week of culture, newly formed mineralized bone was detected in all the scaffolds, both in basal and differentiating media. Bone mineralization was proved to occur preferentially in the trabecular portion and in differentiating media. CONCLUSION: The chosen method, supported by phase contrast micro-CT analysis, successfully and quantitatively monitored the early stages of bone formation and the rate of the bioscaffold resorption in basal and differentiating culture media.

Bulk and interface investigations of scaffolds and tissue-engineered bones by X-ray microtomography and X-ray microdiffraction.

This review is presented of recent investigations concerning the structure of ceramic scaffolds and tissue-engineered bones and focused on two techniques based on X-ray radiation, namely microtomography (microCT) and microdiffraction. Bulk 3D information, with micro-resolution, is mainly obtained by microCT, whereas microdiffraction provides useful information on interfaces to the atomic scale, i.e. of the order of the nanometer. Since most of the reported results were obtained using synchrotron radiation, a brief description of the European Synchrotron Radiation Facility (ESRF) is presented, followed by a description of the two techniques. Then examples of microstructural investigations of scaffolds are reported together with studies on bone architecture. Finally, studies on ex vivo tissue-engineered bone and on bone microstructure in vivo are presented.

Hygiene in dental practices.

AIM: The aim of this study was to investigate the hygienic quality of dental practices on the basis of the self-awareness expressed by dentists respondents to a self-reported questionnaire about the health/hygiene characteristics of practice, the knowledge of biologic/toxicological risks and the preventive procedures and devices improvements in professional practice. MATERIALS AND METHODS: Of the 127 practitioners contacted, 108 (85%) agreed to participate. The knowledge of infective risks was self- evaluated as good only in 24%: even if vaccinated, most of the dentists (57%) considered HBV the main infective agent to fear, not giving the same importance to the air-borne transmission of diseases. The presence of a single dental unit per surgery (90%) was considered an index of good health/hygiene education but, in spite of the use of disposable gloves, caps and masks, the dentists do not always change their coats or wash their hands between patients yet. The management of dental instruments can be considered efficient as long as they are sterilised in an autoclave (97%) and undergo periodic sterilization efficacy tests (76%). RESULTS AND CONCLUSION The results indicate a good structural and organisational status, but there is the need for continuous education concerning the prevention of cross-infections.

Dental caries and bone mineral density: a cross sectional study.

AIM: The relationship between bone mineral density (BMD), age and dental caries has been studied. Quantitative ultrasonography (QUS) is an economic, non invasive, and reproducible method for measuring both bone mineral density and bone elasticity in growing subjects in large populations. METHODS: This study evaluated the relationship between BMD and prevalence of dental caries (Decayed Missing Filled Tooth - DMFT) in 540 healthy adolescent with mean age 12.3 years, age range 10 to 15 years, resident in two provinces in south Italy. BMD was measured using QUS by calculating the speed of sound (m/s) on the last four fingers of the non dominant hand, with the estimate thus obtained being defined as the AD-SoS (Amplitude-Dependent Speed of Sound and categorised as AD-SoS < or = 1900 m/s and AD-SoS > 1900 m/s). Occurrence of dental caries was defined using the DMFT index (DMFT=0 and DMFT > 0). RESULTS: The results of the multifactorial analysis, carried out with logistic model, confirms the expected statistically significant association between response (DMFT) and explicative variables -- AD-SoS (P < 0.006) and Age (P < 0.004). CONCLUSION: Greater bone mineralisation (AD-SoS1900 m/s) and younger age (Age < or =12 years) are dental caries prevention factors: the probability to have caries for the subjects in such conditions is 0.34, about the half of that recorded in the subjects with lower bone mineralisation and older age (0.62).

Biological monitoring of workers in the rubber industry. II. UV-induced unscheduled DNA synthesis in the lymphocytes of vulcanizers.

DNA-repair ability was estimated in a group of vulcanizers by measuring in vitro UV-induced unscheduled. DNA synthesis (UDS) in peripheral lymphocytes, and compared with that of an adequate control group. A considerable interindividual variability was shown by the UDS responses of the subjects studied both in the control and exposed population. Significantly (P = 0.0158) decreased UDS values were observed among the vulcanizers as compared to the referents. Neither age nor cigarette-smoking was observed to affect the UDS response, thus suggesting an association between the industrial exposure and decrease in the DNA-repair rate.

Interactions of ubiquinones with membrane models.

The effect of the insertion of coenzyme Q10 and some of its shorter chain homologues in membrane models (Reverse Micelles, Small Unilamellar Vesicles and Liposomes) has been studied by NMR and IR spectroscopies. By 1H-NMR we have found that the stretched conformation of the isoprenoid side-chain observed in solution is maintained in membrane models. Interaction between the quinonoid moiety of the Q's and the phosphatidic groups of the phospholipids has been evidenced by 31P-NMR. A large effect of this interaction on the water microdynamics and distribution around the charged groups of the phospholipids has been observed by measurements of 1H and 2H relaxation times and by infrared spectra. The 13C-NMR spectra of the backbone of the acyl chains of phospholipids does not seem to be influenced to a noticeable extent by the presence of the Q's.

[Hormone replacement therapy with a transdermal estradiol gel and oral micronized progesterone. Effect on menopausal symptoms and lipid metabolism]. / Die Hormonersatztherapie mit einem perkutan wirksamen Oestradiol-Gel und oral verabreichtem mikronisierten Progesteron. Auswirkung auf klimakterische Symptome und den Lipidstoffwechsel.

In a multicenter observational study, the efficacy and acceptance of two different regimens of postmenopausal hormone replacement therapy in the form of a combination of 17 beta-estradiol in percutaneous gel application and micronized oral progesterone were evaluated. Forty-eight patients (aged 40-66 years) received 2.5 g estradiol gel plus either continuously micronized progesterone 100 per day (group A) or, sequentially, 200 mg per day between day 16 and 25 of a monthly cycle (group B) for two months. A significant reduction in typical menopausal symptoms, especially vasomotor complaints like hot flushes or sweating, was observed in both groups (score average at the beginning for hot flushes: 2.0 in group A and 1.8 in group B; after two months of treatment, 0.7 in group A and 0.4 in group B). Cholesterol levels were slightly reduced but statistically significant (235.9 +/- 49.55 mg/dl vs. 226.3 +/- 52.24 mg/dl; p < 0.05) only in group A; a trend towards lower cholesterol was observed in group B (236.5 +/- 47.82 mg/dl vs. 227.4 +/- 44.72 mg/dl). Lipoprotein (a) was also significantly reduced in group A (32.57 +/- 36.52 mg/dl vs. 28.28 +/- 31.03 mg/dl in group A; 31.7 +/- 28.42 mg/dl vs. 28.34 +/- 23.71 in group B; p < 0.05). The overall acceptance of this therapy was excellent or good in 91.3% of group A and 92.8% of group B patients.

1H-NMR relaxation study of the liposome--nuclei interaction.

Phospholipidic liposomes can influence DNA template availability for RNA synthesis when interacting with isolated nuclei by enhancing (when the phospholipids are negatively charged) or by inhibiting (when they are neutral) trascriptional activity. The analysis of the 1H-NMR relaxation behaviour of isolated nuclei, of Small Unilamellar Vesicles (SUV) and of the SUV-Nuclei system has been undertaken to elucidate the mechanism of the interaction between the nuclear core and the phospholipids.

Influence of biological matrix and artificial electrospun scaffolds on proliferation, differentiation and trophic factor synthesis of rat embryonic stem cells.

Two-dimensional vs three-dimensional culture conditions, such as the presence of extracellular matrix components, could deeply influence the cell fate and properties. In this paper we investigated proliferation, differentiation, survival, apoptosis, growth and neurotrophic factor synthesis of rat embryonic stem cells (RESCs) cultured in 2D and 3D conditions generated using Cultrex® Basement Membrane Extract (BME) and in poly-(L-lactic acid) (PLLA) electrospun sub-micrometric fibres. It is demonstrated that, in the absence of other instructive stimuli, growth, differentiation and paracrine activity of RESCs are directly affected by the different microenvironment provided by the scaffold. In particular, RESCs grown on an electrospun PLLA scaffolds coated or not with BME have a higher proliferation rate, higher production of bioactive nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) compared to standard 2D conditions, lasting for at least 2 weeks. Due to the high mechanical flexibility of PLLA electrospun scaffolds, the PLLA/stem cell culture system offers an interesting potential for implantable neural repair devices.

Engineered liposomes and virosomes for delivery of macromolecules.

In order to utilize virosomes or proteoliposomes for the delivery of drugs or macromolecules to specific pathologic target cells we elaborated a system to shuttle drugs to solid tissue (liver) as well as to the macrophages, a crucial cellular compartment of the immune system. Using virosomes prepared from the P3HR1 strain of Epstein-Barr virus, we demonstrated that these particles fused with human hepatocarcinoma cell line Li7A and therefore might be used as drug vectors. Furthermore, we report that proteoliposomes prepared by reconstituting in a cocktail of phosphatidylserine-phosphatidylcholine the anion transporter band 3 protein markedly increased the phagocytic activity of macrophages in culture. This could represent a new device to be used as a drug delivery system to enhance specific macrophagic functions.

Changes in murine bone marrow macrophages and erythroid burst-forming cells following the intravenous injection of liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP).

In order to explore the effect on bone marrow macrophages of liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP), mice were injected intravenously with a preparation of such liposomes at a dose known to deplete spleen and liver macrophages. Two days later, the macrophages in the marrow of the femoral bones were quantified by flow cytometry using a macrophage-specific monoclonal antibody (F4/80), and their ultrastructure and phagocytic activity towards zymosan particles was assessed. To determine the effect on erythropoiesis of liposome-encapsulated Cl2MDP-induced changes in bone marrow macrophages, red blood cell parameters and the formation of erythroid burst-forming unit (BFU-E)-derived colonies in vitro were evaluated. In mice injected with liposome-encapsulated Cl2MDP, there was a 54% and 67% decrease in the total number of bone marrow macrophages as compared to uninjected controls and mice treated with empty liposomes, respectively. Moreover, residual macrophages showed an abnormal ultrastructure, with reduced numbers of crystalloid inclusions and increased numbers of large myelin figures. However, the phagocytic activity of these cells was unimpaired or slightly enhanced. In mice injected with liposome-encapsulated Cl2MDP there was an approximately 60% decrease in the percentage and total number of circulating reticulocytes and a 54% reduction in the BFU-E number, demonstrating deregulation of erythropoiesis under conditions of macrophage loss and impairment. The results suggest that mice treated with liposome-encapsulated Cl2MDP are a model for studying the role of macrophages in erythropoiesis.