Microscopic and Macroscopic Characterization of Hydrogels Based on Poly(vinyl-alcohol)-Glutaraldehyde Mixtures for Fricke Gel Dosimetry.

In recent decades, hydrogels have emerged as innovative soft materials with widespread applications in the medical and biomedical fields, including drug delivery, tissue engineering, and gel dosimetry. In this work, a comprehensive study of the macroscopic and microscopic properties of hydrogel matrices based on Poly(vinyl-alcohol) (PVA) chemically crosslinked with Glutaraldehyde (GTA) was reported. Five different kinds of PVAs differing in molecular weight and degree of hydrolysis were considered. The local microscopic organization of the hydrogels was studied through the use of the 1H nuclear magnetic resonance relaxometry technique. Various macroscopic properties (gel fraction, water loss, contact angle, swelling degree, viscosity, and Young's Modulus) were investigated with the aim of finding a correlation between them and the features of the hydrogel matrix. Additionally, an optical characterization was performed on all the hydrogels loaded with Fricke solution to assess their dosimetric behavior. The results obtained indicate that the degree of PVA hydrolysis is a crucial parameter influencing the structure of the hydrogel matrix. This factor should be considered for ensuring stability over time, a vital property in the context of potential biomedical applications where hydrogels act as radiological tissue-equivalent materials.

Gel Dosimetry.

The purpose of radiation therapy (RT) is to cover tumor tissue homogeneously with a planned dose while minimizing the dose to the surrounding healthy tissue [...].

Proton Therapy, Magnetic Nanoparticles and Hyperthermia as Combined Treatment for Pancreatic BxPC3 Tumor Cells.

We present an investigation of the effects on BxPC3 pancreatic cancer cells of proton therapy combined with hyperthermia, assisted by magnetic fluid hyperthermia performed with the use of magnetic nanoparticles. The cells' response to the combined treatment has been evaluated by means of the clonogenic survival assay and the estimation of DNA Double Strand Breaks (DSBs). The Reactive Oxygen Species (ROS) production, the tumor cell invasion and the cell cycle variations have also been studied. The experimental results have shown that the combination of proton therapy, MNPs administration and hyperthermia gives a clonogenic survival that is much smaller than the single irradiation treatment at all doses, thus suggesting a new effective combined therapy for the pancreatic tumor. Importantly, the effect of the therapies used here is synergistic. Moreover, after proton irradiation, the hyperthermia treatment was able to increase the number of DSBs, even though just at 6 h after the treatment. Noticeably, the magnetic nanoparticles' presence induces radiosensitization effects, and hyperthermia increases the production of ROS, which contributes to cytotoxic cellular effects and to a wide variety of lesions including DNA damage. The present study indicates a new way for clinical translation of combined therapies, also in the vision of an increasing number of hospitals that will use the proton therapy technique in the near future for different kinds of radio-resistant cancers.

Nanomaterials in Cancer Diagnosis and Therapy.

Currently, the most commonly used treatments for cancer are surgery, radiotherapy, and chemotherapy [...].

Poloxamer-Based Hydrogel as Drug Delivery System: How Polymeric Excipients Influence the Chemical-Physical Properties.

Thermogelling amphiphilic block copolymers have been widely investigated in the development of pharmaceutical drug carriers. In particular, thermosensitive gels based on poloxamer 407 (P407) have great potential for periodontal disease treatment, thanks to their ability to be liquid at room temperature and become viscous gels at body temperature. However, some problems, related to short in situ residence time, reduce their feasible clinical use. Thus, in order to improve the effective applicability of these materials, we studied how P407 thermogels are affected by the pH and by the inclusion of different hydrophilic polymers, used as excipients for increasing the gel stiffness. For this scope, a complete chemical-physical characterization of the synthesized gels is provided, in terms of determination of sol-gel transition temperature, viscosity and erosion degree. The data are correlated according to a statistical multivariate approach based on Principal Component Analysis and their mucoadhesion properties are also tested by Tapping mode-Atomic Force Microscopy (TM-AFM) imaging. Finally, we studied how the different P407 formulations are able to influence the release pathway of two antibacterial drugs (i.e., chlorhexidine digluconate and doxycycline hyclate) largely used in oral diseases.

How Xylenol Orange and Ferrous Ammonium Sulphate Influence the Dosimetric Properties of PVA-GTA Fricke Gel Dosimeters: A Spectrophotometric Study.

The development of Fricke gel (FG) dosimeters based on poly(vinyl alcohol) (PVA) as the gelling agent and glutaraldehyde (GTA) as the cross-linker has enabled significant improvements in the dose response and the stability over time of spatial radiation dose distributions. However, a standard procedure for preparing FG in terms of reagent concentrations is still missing in the literature. This study aims to investigate, by means of spectrophotometric analyses, how the sensitivity to the radiation dose and the range of linearity of the dose-response curve of PVA-GTA-FG dosimeters loaded with xylenol orange sodium salt (XO) are influenced by ferrous ammonium sulphate (FAS) and XO concentrations. Moreover, the effect of different concentrations of such compounds on self-oxidation phenomena in the dosimeters was evaluated. PVA-GTA-FG dosimeters were prepared using XO concentrations in the range 0.04-0.80 mM and FAS in the range 0.05-5.00 mM. The optical absorbance properties and the dose response of FG were investigated in the interval 0.0-42.0 Gy. The results demonstrate that the amount of FAS and XO determines both the sensitivity to the absorbed dose and the interval of linearity of the dose-response curve. The study suggests that the best performances of FG dosimeters for spectrophotometric analyses can be obtained using 1.00-0.40 mM and 0.200-0.166 mM concentrations of FAS and XO, respectively.

Study of Ag Nanoparticles in a Polyacrylamide Hydrogel Dosimeters by Optical Technique.

The dosimetric characteristics of hydrogel dosimeters based on polyacrylamide (PAC) as a capping agent incorporating silver nitrate as a radiation-sensitive material are investigated using UV-Vis spectrophotometry within the dose range 0-100 Gy. Glycerol was used in the hydrogel matrix to promote the dosimetric response and increase the radiation sensitivity. Upon exposing the PAC hydrogel to γ-ray, it exhibits a Surface Plasmon Resonance (SPR) band at 453 nm, and its intensity increases linearly with absorbed doses up to 100 Gy. The results are compared with the silver nitrate gel dosimeter. Glycerol of 15% in the hydrogel matrix enhances the radiation sensitivity by about 30%. PAC hydrogel dosimeter can be considered a near water equivalent material in the 400 keV-20 MeV photon energy range. At doses less than 15 Gy, the PAC hydrogel dosimeter retains higher radiation sensitivity than the gel dosimeter. The total uncertainty (2σ) of the dose estimated using this hydrogel is about 4%. These results may support the validity of using this hydrogel as a dosimeter to verify radiotherapy techniques and dose monitoring during blood irradiation.

Personalized Dosimetry in Targeted Radiation Therapy: A Look to Methods, Tools and Critical Aspects.

Targeted radiation therapy (TRT) is a strategy increasingly adopted for the treatment of different types of cancer. The urge for optimization, as stated by the European Council Directive (2013/59/EURATOM), requires the implementation of a personalized dosimetric approach, similar to what already happens in external beam radiation therapy (EBRT). The purpose of this paper is to provide a thorough introduction to the field of personalized dosimetry in TRT, explaining its rationale in the context of optimization and describing the currently available methodologies. After listing the main therapies currently employed, the clinical workflow for the absorbed dose calculation is described, based on works of the most experienced authors in the literature and recent guidelines. Moreover, the widespread software packages for internal dosimetry are presented and critical aspects discussed. Overall, a selection of the most important and recent articles about this topic is provided.

Netupitant/palonosetron without dexamethasone for preventing nausea and vomiting in patients with multiple myeloma receiving high-dose melphalan for autologous stem cell transplantation: a single-center experience.

Chemotherapy-induced nausea and vomiting (CINV) is one of the most frequent adverse events compromising quality of life (QoL) in patients undergoing autologous stem cell transplantation (ASCT). However, CINV prophylaxis is still lacking uniformity for high-dose melphalan (HDM), which is used to condition patients with multiple myeloma (MM). Netupitant/palonosetron (NEPA) is administered with dexamethasone (DEXA) for CINV prevention in several chemotherapy regimens. Our study aims to assess the efficacy of NEPA, without DEXA, in preventing CINV in 106 adult patients with MM receiving HDM and ASCT. All patients had antiemetic prophylaxis with multiple doses of NEPA 1 h before the start of conditioning and after 72 h and 120 h. A complete response (CR) was observed in 99 (93%) patients at 120 h (overall phase). The percentage of patients with complete control was 93%. The CR rate during the acute phase was 94% (n = 100). During the delayed phase, the CR rate was 95% (n = 101). Grade 1 nausea and vomiting were experienced by 82% and 12% of the patients, respectively. Grade 2 nausea was reported in 18% and vomiting in 10% of patients. Our results showed, for the first time, that NEPA, without DEXA, was a well-tolerated and effective antiemetic option for MM patients receiving HDM followed by ASCT.

The Burden in Caregivers of Multiple Myeloma Patients Undergoing Outpatient Autologous Stem-Cell Transplantation Compared to Inpatient Transplantation.

BACKGROUND: The application of different models of autologous stem-cell transplantation (ASCT) in multiple myeloma has demonstrated the feasibility and safety of outpatient-based programs of care. Although several systematic reviews have evaluated the burden of caregivers, only a few studies have included outpatient ASCT. PATIENTS AND METHODS: The feelings of lack of family support, daily activities, and general health were compared between caregivers of 2 groups of patients with multiple myeloma who underwent inpatient (n = 71) or outpatient (n = 25) ASCT. RESULTS: The 3 features did not significantly differ between the 2 study groups at baseline, before, and 3 months after ASCT. Multivariate modeling showed that the baseline values were significantly related to the changes in study outcomes independent of patient and caregiver characteristics. Other correlates were caregivers' work and patient age for impact on daily activities and disease burden across time for impact on general health (all P < .05). CONCLUSION: The outpatient model neither improves nor impairs global caregivers' burden compared to standard ASCT care. Further research is needed to confirm this observation and to better assess the burden and quality of life of caregivers and their influence on patient outcomes and quality of life.

Hadron Therapy, Magnetic Nanoparticles and Hyperthermia: A Promising Combined Tool for Pancreatic Cancer Treatment.

A combination of carbon ions/photons irradiation and hyperthermia as a novel therapeutic approach for the in-vitro treatment of pancreatic cancer BxPC3 cells is presented. The radiation doses used are 0-2 Gy for carbon ions and 0-7 Gy for 6 MV photons. Hyperthermia is realized via a standard heating bath, assisted by magnetic fluid hyperthermia (MFH) that utilizes magnetic nanoparticles (MNPs) exposed to an alternating magnetic field of amplitude 19.5 mTesla and frequency 109.8 kHz. Starting from 37 °C, the temperature is gradually increased and the sample is kept at 42 °C for 30 min. For MFH, MNPs with a mean diameter of 19 nm and specific absorption rate of 110 ± 30 W/gFe3o4 coated with a biocompatible ligand to ensure stability in physiological media are used. Irradiation diminishes the clonogenic survival at an extent that depends on the radiation type, and its decrease is amplified both by the MNPs cellular uptake and the hyperthermia protocol. Significant increases in DNA double-strand breaks at 6 h are observed in samples exposed to MNP uptake, treated with 0.75 Gy carbon-ion irradiation and hyperthermia. The proposed experimental protocol, based on the combination of hadron irradiation and hyperthermia, represents a first step towards an innovative clinical option for pancreatic cancer.

Characterization of phenolic pellets for ESR dosimetry in photon beam radiotherapy.

This work deals with the dosimetric features of a particular phenolic compound (IRGANOX 1076®) for dosimetry of clinical photon beams by using electron spin resonance (ESR) spectroscopy. After the optimization of the ESR readout parameters (namely modulation amplitude and microwave power) to maximise the signal without excessive spectrum distortions, basic dosimetric properties of laboratory-made phenolic dosimeters in pellet form, such as reproducibility, dose-response, sensitivity, linearity and dose rate dependence were investigated. The dosimeters were tested by measuring the depth dose profile of a 6 MV photon beam. A satisfactory intra-batch reproducibility of the ESR signal of the manufactured dosimeters was obtained. The ESR signal proved to increase linearly with increasing dose in the investigated dose range 1-13 Gy. The presence of an intrinsic background signal limits the minimum detectable dose to a value of approximately 0.6 Gy. Reliable and accurate assessment of the dose was achieved, independently of the dose rate. Such characteristics, together with the fact that IRGANOX 1076® is almost tissue-equivalent, and the stability of the ESR signal, make these dosimeters promising materials for ESR dosimetric applications in radiotherapy.

Real-time dosimetry with Yb-doped silica optical fibres.

Over the years, many efforts have been made to develop radiation detectors to handle the complex issues of small field dosimetry and achieve the increasing accuracy, precision and in vivo dose monitoring required by the new advanced treatment modalities. In this context, interest has surged in the development of sensors based on scintillating optical fibres. In this paper, the near-infrared radioluminescence and dosimetric properties of Yb-doped silica optical fibres, coupled with a laboratory prototype based on an avalanche photodiode, were studied by irradiating the fibres with photons and electron beams generated by a Varian Trilogy accelerator. The performance of the system in standard and small field sizes has also been investigated, comparing the output factor, percentage depth dose and off-axis ratio measurements of the prototypal detector with other commercial sensors, including the Exradin W1 scintillator. The results of this study demonstrate that the drawback due to the stem effect in Yb-doped silica optical fibres can be managed in a simple but effective way by optical filtering. The robustness of the system in complex dosimetric scenarios and the accuracy and precision achieved by Yb-doped fibres in relative dose assessments suggest an effective use of the system for real-time in vivo dosimetry applications.

Rabeprazole and psychiatric symptoms.

OBJECTIVE: To report the case of a patient who developed marked anxiety associated with episodes of panic attacks after starting rabeprazole therapy. CASE SUMMARY: An otherwise healthy 55-year-old woman was prescribed rabeprazole 20 mg/day administered in the morning for persistent symptoms of dyspepsia. Ten days later, she presented with a 7 day history of marked anxiety associated with panic attacks, night terror (pavor nocturnus), episodic mental confusion, and attention deficit. Within 2 days of discontinuing rabeprazole, the patient recovered completely from the neuropsychiatric manifestations. Subsequent esomeprazole therapy did not cause psychiatric symptoms. DISCUSSION: Rabeprazole-induced hypergastrinemia may have played a role in this neuropsychiatric adverse reaction. Several lines of evidence have indicated that gastrin-releasing peptide, whose release is mediated by proton pump inhibitor (PPI)-induced secretion of gastrin, is involved in regulating aspects of behavior that might be altered in disorders such as anxiety, depression, and dementia. The fact that rabeprazole has the highest capacity of inducing gastrin increase compared with other PPIs might explain why our patient's panic symptoms disappeared after switching to esomeprazole. Based on the Naranjo probability scale, rabeprazole was the probable cause of the adverse reaction. CONCLUSIONS: Specific studies are needed to investigate the potential role of PPI-induced hypergastrinemia in neuropsychiatric adverse reactions.