Tailored-BODIPY/Amphiphilic Cyclodextrin Nanoassemblies with PDT Effectiveness.

Amphiphilic cyclodextrins (aCDs) are an intriguing class of carrier systems which, recently, have been proposed to deliver porphyrinoids and anticancer drugs or combined dose of both for dual therapeutic applications. The design of nanoassemblies based on aCD and photosensitizers (PSs) aims to preserve the photodynamic therapy (PDT) efficacy of PS, reducing the tendency of PS to self-aggregate, without affecting the quantum yield of singlet oxygen (1O2) production, and, not less importantly, minimizing dark toxicity and reducing photosensitization effects. With this idea in mind, in this paper, we focus on nanoassemblies between a non-ionic aCD (SC6OH) and halo-alkyl tailored iodinated boron-dipyrromethenes (BODIPY) dye, a class of molecules which recently have been successfully proposed as a stimulating alternative to porphyrinoids for their high photodynamic efficacy. Nanoassemblies of BODIPY/aCD (BL01I@SC6OH) were prepared in different aqueous media by evaporation of mixed organic film of aCD and BODIPY, hydration, and sonication. The nanostructures were characterized, measuring their hydrodynamic diameter and ξ-potential and also evaluating their time-stability in biological relevant media. Taking advantage of emissive properties of the not-iodinated BODIPY analogue (BL01), nanoassemblies based on aCD and BL01 were investigated as model system to get insight on entanglement of BODIPY in the amphiphile in aqueous dispersion, pointing out that BODIPY is well-entrapped in monomeric form (τ ≅ 6.5 ns) within the colloidal carriers. Also morphology and fluorescence emission properties were elucidated after casting the solution on glass. BL01@SC6OH is easily detectable in cytoplasm of HCT116 cell lines, evidencing the remarkable intracellular penetration of this nanoassembly similar to free BODIPY. On the same cell lines, the photodynamically active assembly BL01I/aCD shows toxicity upon irradiation. Despite the fact that free BL01I is more PDT active than its assembly, aCD can modulate the cell uptake of BODIPY, pointing out the potential of this system for in vivo PDT application.

Is retrograde intrarenal surgery a viable treatment option for renal stones in patients with solitary kidney?

PURPOSE: To evaluate the effectiveness and safety of retrograde intrarenal surgery (RIRS) for stones up to 2 cm in diameter in patients with solitary kidney. METHODS: From January 2008 to January 2013, we prospectively enrolled all consecutive patients with solitary kidney and renal stones. Plain abdominal computed tomography scan was performed preoperatively and 1 month after the procedure to assess the stone-free rates (SFR). Serum creatinine levels were detected preoperatively, at day 1 postoperatively, at 1 month postoperatively, and then every 6 months postoperatively. RESULTS: During the study period, we prospectively enrolled a total of 29 patients. The mean age was 55.7 ± 12.3 years; the mean stone size was 1.3 ± 0.4 cm. The primary SFR was 72.4 %; the secondary SFR was 93.1 %. The mean number of procedures per patient was 1.24. The mean serum creatinine levels were 1.5 ± 0.6, 1.6 ± 0.7, 1.6 ± 0.6, and 1.7 ± 0.7 mg/dl preoperatively, at 1 day after RIRS, at 1 month after RIRS, and at 1 year after RIRS, respectively, without detection of any statistical difference (p = 0.76). Median follow-up time was 35.7 ± 19.3 (12-72) months, but that was available for only 18 patients. The mean serum creatinine level at the last follow-up was 1.7 ± 0.9 mg/dl. No major complications were recorded. Grade I complications occurred in eight patients (27.4 %). CONCLUSIONS: RIRS is safe and effective in the treatment of renal stones in patients with solitary kidney, without worsening renal function.

Mammary Paget's disease and radiotherapy: a systematic literature review.

OBJECTIVE: Paget disease of the breast (PDB) is a rare form of cutaneous breast cancer. Up to date, no randomized studies evaluated the different management strategies. This systematic review investigates the role of radiotherapy and its best technical profile in the treatment of this disease, with great attention to doses and fractionation regimens. MATERIALS AND METHODS: A systematic search was performed on PubMed, Embase and Scopus in order to detect case reports, case series and prospective as well as retrospective clinical studies describing histologically proven PDB and providing information about pertinent radiation treatments. Searching strategy followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. RESULTS: Inclusion criteria were met by six papers, dealing with radiation treatments performed postoperatively and in exclusive settings. No evaluations were performed on preoperative radiotherapy. CONCLUSIONS: Actually, the standard treatment of PDB reflects oncological principles of breast carcinoma therapy, including the role of breast-preserving surgery. The traditional radiotherapic dose is 50 Gy, with daily fractionation of 2 Gy. Adjuvant radiotherapy following breast preserving surgery represents the current standard of care; prospective studies could be of help in defining the role of exclusive radiotherapy, hypofractionated schemes and smaller target volumes.

Elevated vascular endothelial growth factor (VEGF) serum levels in idiopathic myelofibrosis.

An increase of angiogenesis has been shown in idiopathic myelofibrosis with myeloid metaplasia (MMM) by microvessel density count method but evaluation of circulating angiogenic factors is still incomplete. In 31 patients affected by MMM and in 12 healthy subjects we evaluated the serum levels of VEGF (vascular endothelial growth factor) and correlated VEGF with clinical and laboratory features of disease. We found that MMM patients had circulating VEGF concentrations much higher than controls (Median 1208 ng/ml vs 138 ng/ml, P < 0.0001). No correlation was found between VEGF and Hb, WBC, PLT, LDH, creatinine, bone marrow cellularity, fibrosis, splenomegaly, hepatomegaly, and therapy. However, in the subgroup of patients with a normal or low VEGF concentration, a direct correlation between VEGF and platelet count (r = 0.90, P = 0.002) was detected. Moreover, patients with a platelet count < 300 x 10(9)/l had VEGF serum levels lower than patients with a higher PLT count (median VEGF 864 vs 1557 pg/ml, P = 0.001). In six patients and in eight controls we also had the opportunity to measure VEGF in the plasma and we calculated that VEGF concentration was much higher in platelet-rich than in platelet-poor plasma and that platetets of MMM patients contained four times more VEGF than those of healthy controls. These results indicate that VEGF is overproduced in MMM, thus confirming an increased angiogenic activity. Platelets are probably a major source of VEGF in MMM but not the only one.

[Clinical statistical evaluation of the antiplaque efficacy of therapeutic aids]. / Valutazione clinico-statistica sull'efficacia anti-placca di alcuni presidi terapeutici.

The results of a blind comparison of different types of toothpaste carried out for two months are reported. It was noted that the paste based on azulene, sodium chloride and benzalkonium chloride produces a more marked regression in the gingival index, whereas that based on chlorhexidine produces a more marked reduction in the plaque index. The differences were not statistically significant, however. With an equal quantity of tooth-paste, it was shown that two initial sessions of ultrasonic detartrasis produce a statistically significant benefit as regards gingival index regression, but an only apparent one for the plaque index. Detartrasis alone, not followed by regular oral hygiene practice, leads to momentary benefits but, as the weeks go by, the difference between the indices of those submitted to detartrasis alone and those who also adopt recommended toothpastes regularly becomes increasingly significant.

[Effects of administration of gastric mucoprotein and vitamin B 12 on rats fed Hauk's and Osers standard diet and Wynn's cariogenic diet]. / Effetti della somministrazione di mucoproteina gastrica e vit. B12 nei ratti alimentati con dieta standard di Hauk e Oser e con dieta cariogena di Wynn (emory)

An increase in dental decay of 48.89% over controls fed with a cariogenic diet was noted when gastric mucoprotein and vitamin B12 were administered to rats receiving a standard diet.

[Nimesulide: multicenter clinical study for evaluation of its therapeutic effect in odontostomatology]. / Nimesulide: studio clinico multicentrico per la valutazione dell'attività terapeutica in odontostomatologia.

A Polycentric Study was carried out so as to assess the anti-inflammatory effectiveness and pain-killing activity of Nimesulide in Odontostomatological practice, in 78 patients suffering from alveolo-gingival and parodontal abscesses, consequences of tooth extraction, suppurated radicular cysts, dysodontiasis, osteitis, periodontitis, periostitis. The results obtained confirm the anti-inflammatory and analgesic effect as well as the good tolerability of this drug.

Cystoman® and calculi: a good alternative to standard therapies in preventing stone recurrence.

To assess the efficacy and tolerability of D-mannose-containing product (Cystoman(®)) in preventing recurrence in patients who underwent surgical treatment for infection related urinary stones. From January 2011 to February 2013 we have enrolled all consecutive patients affected by staghorn calculi and recurrent urinary tract infections (UTIs). All patients recommended for surgery were scheduled for percutaneous nephrolithotomy. The study agent was administered daily for 5 months after surgical procedure. At baseline and 5-month follow-up all patients underwent abdominal Computed Tomography (CT) scan and they also completed Medical Outcomes Study short-form, 36-item questionnaire (SF-36). They performed urine and urine culture monthly. The primary endpoints were the assessment of the efficacy with regard to infection-related urinary stone recurrence and the tolerability of Cystoman(®). The secondary endpoint was the evaluation of quality-of-life symptoms. During the study period, a total of 27 patients were included in the study. The data from 25 patients were analyzable. Seventeen patients (68%) did not report UTIs during follow-up. Eight patients (32%) remained infected and the average number of UTIs was 2.6 ± 1.6 in 5 months. At 5-month follow-up 17 (68%) patients were free from stones recurrence; in 8 (32%) cases CT scan revealed stone recurrence with an average stone diameter of 1.1 ± 0.4 cm. In nonrecurring patients, 2 (11.7%) reported an average of 1.5 ± 0.7 UTIs episodes; in recurring patients, 6 (75%) showed 3 ± 1.67 of UTIs episodes. Statistically significant differences were seen in the occurrence of UTIs episodes were detected between nonrecurring stone patients and recurring patients (p < 0.05). Moreover, statistically significant changes were detected in SF-36 scores from baseline to month 5 in the categories of physical functioning and energy/fatigue (p < 0.05). Cystoman(®) is effective in preventing infection-related urinary stones.

Epidural analgesia with ropivacaine and sufentanil is associated with transient fetal heart rate changes.

AIM: Fetal heart rate (FHR) changes have been reported after regional labor analgesia. In this prospective single-blinded study, we aimed to assess whether epidural analgesia with ropivacaine and sufentanil is associated with significant changes in fetal heart rate. METHODS: Fetal heart rate traces from 120 women in active labor requesting epidural analgesia were recorded and analyzed by two reviewers 90 minutes before and after epidural analgesia for baseline fetal heart rate, accelerations, decelerations and long-term variability. RESULTS: A significantly decreased number of fetal heart rate accelerations (ANOVA P=0.0001) and a higher percentage of segments with decelerations (P<0.05) were observed in the three segments after analgesia as compared to the three preceding segments. The minimum number of accelerations occurred during the 30 minutes immediately after analgesia was initiated. The reviewers were concordant in finding a significant change from the 60 minutes before to the 60 minutes after analgesia, a period in which there CONCLUSION: Epidural analgesia with ropivacaine and sufentanil is associated with fetal heart rate changes. These modifications are transient and should be considered when evaluating fetal heart rate monitoring during labor to prevent inappropriate obstetric management decisions to proceed with operative labor.

Identification of a new allele in a Sicilian individual: HLA-DPB1*0302.

We report here the identification and characterization of a novel human leucocyte antigen (HLA)-DPB1 allele that was subsequently named HLA-DPB1*0302 by the WHO Nomenclature Committee. HLA-DPB1*0302 was identified in a single Sicilian individual by a combination of sequence-specific primers, reverse line sequence-specific oligonucleotide probing and DNA sequencing-based typing. The DPB1*0302 allele is most similar to the DPB1*3101 allele, differing by a single mismatch at nucleotide position 301 (T to G).

[Use of a particular cellulose acetate supporting agent in the electrophoretic evaluation of urinary proteins]. / Impiego di un particolare supporto di acetato di cellulosa nella valutazione elettroforetica delle proteine urinarie.

It is compared an electrophoretic study between unconcentrated and concentrated urine samples on cellulose acetate and immunoelectrophoresis. The study shows that the findings carried out on cellulose acetate are overlapped with the immunochemical methods therefore the cellulose acetate may be preferred an useful medium on the electrophoretic assay of the unconcentrated urinary proteins without concentration.

[Bidimensional electrophoresis of factor VIII antigen on cellulose acetate]. / Elettroforesi bidimensionale del fattore VIII antigene su acetato di cellulosa.

It is described two-dimensional immunoelectrophoresis using cellulose acetate as supporting medium compared with agarose gel method. The results show that the determination of the FVIIIR: Ag on cellulose acetate is a technique more simple and rapid than agarose gel method and many free from the technical failure.

[Use of a particular cellulose acetate supporting agent in the electrophoretic evaluation of human hemoglobin]. / Impiego di un particolare supporto di acetato di cellulosa nella valutazione elettroforetica dell'emoglobina umana.

576 subjects of whom 450 with hereditary anaemia and 116 normal are studied to establish the haemoglobin pattern. The assay is carried out using the standard cellulose acetate and an particular cellulose acetate medium cellogel RS "Wedge". The results show that cellogel RS in comporation with standard medium permits either an better resolution of the hemoglobin bands or a better detection of the pathologic bands.

[Oral surgery and histologic reports: the incidence of various diseases in eastern Sicily]. / Chirurgia orale e referti istologici: considerazioni sull'incidenza delle varie pathologie in Sicilia orientale.

According to the histological exams executed from January 1975 to June 1988, the authors assessed the frequency in the years, in the sex and in the decades and of the pathology surgery executed. For simplicity of graphic representation, the authors subdivided the pathologies in nine groups: phlogistic trial, cysts, epulis, leukoplakia and precancerous lesion, epithelial tumor, connectival tumor, vascular tumor and osseous tumor. With the voice "other" we consider some neoplasies which are not numerous and which are not differently classificable. According to the present statistics numerous operations are excluded like dysodontiasis, dental embedding, fractures, supernumerary teeth and so on. The authors ascertained on elevated frequency of cysts and of osteitis of maxillary bone caused by an inadequate and late treatment of the cavity. During the passing of the years the incidence of phlogistic trial is particularly reduced while the cysts presented a notable increase. Comparison of leukoplakia was exceptional while among the tumors predominate the epithelial tumors one. According to the presented information the Authors come to an end hoping a more preventive sensibility of people and dentistries.

Recurrent pelvic pain in women.

We conducted a prospective survey from January to September 1999 on a random population from the city of Turin, Italy, to highlight pain pathologies at various ages and possible differences between sexes. By means of a questionnaire, women were asked about age, profession, marital status, menstrual pain, type of delivery, number of children, onset and presence of pain of any type. Pain-related questions included its characteristics, familial tendencies, treatment, type, duration, daily and monthly quantity of medication taken, habits, previous pathologies, or surgical operations. A control group of men was investigated.

[HbA2 evaluation: comparison between microchromatography on a DEAE cellulose column and conventional cellulose acetate electrophoresis]. / Valutazione della Hb A2: comparazione fra microcromatografia su colonna deae cellulosa ed elettroforesi convenzionale su acetato di cellulosa.

Even if different methods were employed in Hb A2 level detection, so far the borderline values between normal and pathological "range" depend on the different laboratories and techniques. The Authors report here an investigation carried out on Hb A2 levels using two different methods: the chromatographic technique by DEAE cellulose column, and the cellulose acetate electrophoresis. The investigation regards 46 normal and 50 beta-thalassemia obligate carrier samples. The results demonstrate that chromatographic technique provides a lowest misclassification rate with a greater reliability. Therefore the use of the microchromatographic procedure for beta-thalassemia screening is recommended.

T-subset abnormalities in thalassaemia intermedia: possible evidence for a thymus functional deficiency.

Peripheral blood T-lymphocyte subsets, evaluated by means of a series of monoclonal antibodies, were assessed in 14 patients affected by thalassaemia intermedia, 7 of them previously splenectomized. A significant reduction of T+4 cells ('helper' T cells) was found in almost all patients, whereas T+8 cells ('suppressor/cytotoxic') showed a marked increase only in splenectomized subjects. Together with these quantitative T-subset abnormalities, which seemed to be partly affected by either splenectomy or high serum iron levels, an unusual circulating T-cell subpopulation labelled by T6 monoclonal antibody was detected in all patients. Complete disappearance of T+6 cells ('thymocyte-like' T lymphocytes) and normalization of the T4/T8 ratio was observed after 'in vitro' incubation of patient's lymphocytes with a crude thymus extract (Thymostimulin). This would suggest the presence of a so far unreported thymus-dependent defect of T-lymphocyte phenotypic maturation occurring in thalassaemia intermedia.