[Challenges and strategies to recover and dynamize primary care: SWOT-CAME analysis in a Health Department]. / Retos y estrategias para recuperar y dinamizar la atención primaria. Metodología DAFO (Debilidades, Amenazas, Fortalezas y Oportunidades)-CAME (Corregir, Afrontar, Mantener y Explotar) en un departamento de salud.

OBJECTIVE: To identify strengths, obstacles, changes in the environment, and capabilities of primary care teams and support units, with the aim of providing high-quality care in an integrated healthcare area. DESIGN: Mixed methods study based on the SWOT matrix and CAME analysis. LOCATION: Primary care, Valencian community. PARTICIPANTS: A total of 271 professionals from different collectives and patient association representatives participated. 99 in the idea generation phase, 154 in the SWOT matrix development phase, and 18 in the CAME analysis development phase. INTERVENTIONS: A SWOT-CAME analysis was conducted, from which action lines were established. Information capture was carried out through nominal groups, and the consensus phase involved integrating all professionals through Delphi and consensus conference techniques. MAIN MEASUREMENTS: Prioritization of proposals to maintain strengths, address threats, exploit opportunities, and correct weaknesses within the framework of an integrated healthcare area action plan. RESULTS: A total of 82 different ideas were proposed (20 strengths; 40 weaknesses; 4 threats; 12 opportunities; 6 threats-opportunities), which, once prioritized, were translated into 7 lines and 33 prioritized actions/interventions (CAME analysis). CONCLUSIONS: Integrated care, seeking collaborative approaches between care levels, redefining roles, digital solutions, staff training, and improvements in equipment and support processes, along with measures to address the aging population and the needs of socio-sanitary centers, constitute the challenges to be addressed.

Advancements in cell membrane camouflaged nanoparticles: A bioinspired platform for cancer therapy.

The idea of employing natural cell membranes as a coating medium for nanoparticles (NPs) endows man-made vectors with natural capabilities and benefits. In addition to retaining the physicochemical characteristics of the NPs, the biomimetic NPs also have the functionality of source cell membranes. It has emerged as a promising approach to enhancing the properties of NPs for drug delivery, immune evasion, imaging, cancer-targeting, and phototherapy sensitivity. Several studies have been reported with a multitude of approaches to reengineering the surface of NPs using biological membranes. Owing to their low immunogenicity and intriguing biomimetic properties, cell-membrane-based biohybrid delivery systems have recently gained a lot of interest as therapeutic delivery systems. This review summarises different kinds of biomimetic NPs reported so far, their fabrication aspects, and their application in the biomedical field. Finally, it briefs on the latest advances available in this biohybrid concept.

pH-temperature dual-sensitive nucleolipid-containing stealth liposomes anchored with PEGylated AuNPs for triggering delivery of doxorubicin.

Liposomes (Lip) are useful nanocarriers for drug delivery and cancer nanomedicine because of their ability to efficiently encapsulate drugs with different physical and chemical properties. The pH gradient between normal and tumoral tissues, and their rapid metabolism that induces hyperthermia encourage the development of pH- and thermo-sensitive Lip for delivering anticancer drugs. Nucleolipids have been studied as scaffolding material to prepare Lip, mainly for cancer therapy. Herein, we report for the first time the use of 1,2-dipalmitoyl-sn-glycero-3-(cytidine diphosphate) (DG-CDP) to develop pH/thermo-sensitive nucleolipid-containing stealth Lip stabilized by combination with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol, anchored with NH2-PEGylated gold nanoparticles (PEG-AuNPs, 15 nm) for triggering delivery of doxorubicin (Dox). The optimal composition of DPPC, DG-CDP and cholesterol (94:3:3) was established by Langmuir isotherms. Unloaded and Dox-loaded Lip and AuNPs-Lip exhibited nano-scale sizes (415-650 nm), acceptable polydispersity indexes (<0.33), spherical shapes, and negative Z-potential (-23 to -6.6 mV) due to the phosphate groups of DG-CDP, which allowed the anchoring with positively charged AuNPs. High EE% were achieved (>78%) and although efficient control in the Dox release towards different receptor media was observed, the release of Dox from PEG-AuNPs-Lip-Dox was significantly triggered at acidic pH and hyperthermia conditions, demonstrating its responsiveness to both stimuli. Dox-loaded Lip showed high cytotoxic activity against MDA-MB-231 breast cancer cells and SK-OV-3 ovarian cancer cells, suggesting that Dox was released from these nanocarriers over time. Overall, the liposomal formulations showed promising properties as stimuli-responsive nanocarriers for cancer nanomedicine, with prospects for hyperthermia therapy.

Psilostachyins as trypanocidal compounds: Bioguided fractionation of Ambrosia tenuifolia chemically modified extract.

This work focusses on the chemical diversification of an Ambrosia tenuifolia extract and its bioguided fractionation, aiming to unveil the chemical entity responsible for the trypanocidal activity. Besides, a revision of the phytochemical study of this species, based on previous reports of the antiparasitic psilostachyins A and C as main compounds, was conducted. To improve the biological properties of a plant extract through a simple chemical reaction, the oxidative diversification of the dichloromethane extract of this plant species was carried out. A bioguided fractionation of a chemically modified extract was performed by evaluating the inhibitory activity against Trypanosoma cruzi trypomastigotes. This experiment led to the isolation of one of the most active compounds. In general terms, epoxidized metabolites were obtained as a result of the oxidation of the major metabolite of the species. The trypanocidal activity of some tested metabolites overperformed the reference drug, benznidazole, displaying no cytotoxicity at trypanocidal concentrations. Key structure-activity relationships were obtained for designing previously undescribed antiparasitic sesquiterpene lactones.

Evaluation of a patient-centered integrated care program for individuals with frequent hospital readmissions and multimorbidity.

Managing patients with multimorbidity and frequent hospital readmissions is a challenge. Integrated care programs that consider their needs and allow for personalized care are necessary for their early identification and management. This work aims to describe these patients' clinical characteristics and evaluate a program designed to reducing readmissions. This prospective study analyzed all patients with ≥ 3 admissions to a medical department in the previous year who were included in the Internal Medicine Department chronic care program at the Lucus Augusti University Hospital (Lugo, Spain) between April 1, 2019 and April 30, 2021. A multidimensional assessment, personalized care plan, and proactive follow-up with a case manager nurse were provided via an advanced hospital system. Clinical and demographic variables and data on healthcare system use were analyzed at 6 and 12 months before and after inclusion. Descriptive and survival analyses were performed. One hundred sixty-one patients were included. Program participants were elderly (mean 81.4 (SD 11) years), had multimorbidity (10.2 (3) chronic diseases) and polypharmacy (10.6 (3.5) drugs), frequently used the healthcare system, and were highly complex. Most were included for heart failure. The program led to significant reductions in admissions and emergency department visits (p = .0001). A total of 44.7% patients died within 1 year. The PROFUND Index showed good predictive ability (p = .013), with high values associated with mortality (RR 1.15, p = .001). Patients with frequent hospital readmissions are highly complex and need special care. A personalized integrated care program reduced admissions and allowed for individualized decision-making.

Depth of thermal dispersion of monopolar radiofrequency heating in the vaginal wall.

The use of energy-based devices to treat genitourinary syndrome of menopause, termed vaginal thermotherapy (VTT), has gained significant interest in recent years. Among the primary safety concerns of this relatively new procedure is the possibility of unintentionally heating tissues adjacent to the vaginal wall, i.e., heating too deeply. Herein we use numerical simulations to evaluate monopolar radiofrequency-based (RF) VTT specifically focusing on the resultant depth of heating through a range of input parameters. Varying RF power, exposure time, and the simulated rate of blood perfusion, we map the parameter space identifying which combinations of input parameters are likely to heat past the depth of the vaginal wall and affect adjacent tissue. We found that the device parameters commonly used in the literature are likely to heat past the vaginal wall and merit further investigation. In addition, we found that the parameter typically used to describe VTT devices, total energy delivered, does not reliably indicate the resultant depth of heat dispersion.

Safety and Effectiveness of a Single Multiallergen Subcutaneous Immunotherapy in Polyallergic Patients.

BACKGROUND: As the number of allergic sensitizations increases the severity of allergic respiratory diseases worsens. Multiple monoallergen immunotherapy can be accompanied by poor treatment adherence and high costs, single multiallergen immunotherapy needs to prove efficacy whilst maintaining a good safety profile. METHODS: Observational, retrospective, multicenter study using a 2-pollen single undiluted multiallergen subcutaneous immunotherapy (SCIT) in routine clinical practice in Spain. Patients with rhinoconjunctivitis, with/without controlled asthma, sensitized to grass, olive, Parietaria, Cupressus, plane tree and/or Salsola pollen were included. Primary and secondary clinical efficacy endpoints were quality of life (mini Rhinitis Quality of Life Questionnaire (miniRQLQ)) and visual analogue scale (VAS) respectively. All adverse events were documented. RESULTS: Ten centers included 97 patients, median age 32 years. SCIT treatment included combinations of grass mix with olive, Parietaria, Cupressus, plane tree or Salsola or olive with Parietaria, Cupressus or Salsola. The mean duration of SCIT was 1.8 years with a high treatment adherence (73%). Significant improvement in quality of life, nasal and ocular symptoms, activity limitations and practical problems (p< 0.0001) and other symptoms (p= 0.024) was observed. Most patients did not develop asthma-like symptoms and a significant improvement of all allergic symptom severity was perceived. VAS showed a significant improvement in rhinoconjunctivitis and asthma by patients and physicians. Twenty-nine patients experienced adverse reactions, 25 had local and 6 had systemic reactions. CONCLUSIONS: Single undiluted multiallergen SCIT treatment of two different pollens is efficacious and safe in both children and adults, showing that it is a suitable option for the treatment of polyallergic patients.

In Vivo Efficacy and Toxicity of Curcumin Nanoparticles in Breast Cancer Treatment: A Systematic Review.

Breast cancer is one of the most prevalent types of malignant tumors in the world, resulting in a high incidence of death. The development of new molecules and technologies aiming to apply more effective and safer therapy strategies has been intensively explored to overcome this situation. The association of nanoparticles with known antitumor compounds (including plant-derived molecules such as curcumin) has been considered an effective approach to enhance tumor growth suppression and reduce adverse effects. Therefore, the objective of this systematic review was to summarize published data regarding evaluations about efficacy and toxicity of curcumin nanoparticles (Cur-NPs) in in vivo models of breast cancer. The search was carried out in the databases: CINAHL, Cochrane, LILACS, Embase, FSTA, MEDLINE, ProQuest, BSV regional portal, PubMed, ScienceDirect, Scopus, and Web of Science. Studies that evaluated tumor growth in in vivo models of breast cancer and showed outcomes related to Cur-NP treatment (without association with other antitumor molecules) were included. Of the 528 initially gathered studies, 26 met the inclusion criteria. These studies showed that a wide variety of NP platforms have been used to deliver curcumin (e.g., micelles, polymeric, lipid-based, metallic). Attachment of poly(ethylene glycol) chains (PEG) and active targeting moieties were also evaluated. Cur-NPs significantly reduced tumor volume/weight, inhibited cancer cell proliferation, and increased tumor apoptosis and necrosis. Decreases in cancer stem cell population and angiogenesis were also reported. All the studies that evaluated toxicity considered Cur-NP treatment to be safe regarding hematological/biochemical markers, damage to major organs, and/or weight loss. These effects were observed in different in vivo models of breast cancer (e.g., estrogen receptor-positive, triple-negative, chemically induced) showing better outcomes when compared to treatments with free curcumin or negative controls. This systematic review supports the proposal that Cur-NP is an effective and safe therapeutic approach in in vivo models of breast cancer, reinforcing the currently available evidence that it should be further analyzed in clinical trials for breast cancer treatments.

Optimization of the antioxidant capacity of mangosteen peels (Garcinia mangostana L.) extracts: Management of the drying extraction processes.

Mangosteen peel is a source of natural phenolic antioxidants. During processing, the quality and quantity of these compounds in the final product are altered. Sometimes, the important causal relationships are not easy to establish and thus process management is difficult. This is especially true when biochemical changes can occur as in the case of the drying and extraction process of bioactive materials. The aim of this work was to formulate and solve an optimization problem in order to obtain the appropriate values of the operating conditions that maximize the antioxidant capacity of the dried mangosteen peel extracts. The drying process was analyzed under different drying air temperatures (T) (50℃, 60℃, 70℃ and 80℃) at air velocity of 1 ms-1. The extraction process was done under conventional and ultrasound-assisted extraction at 400 W. Antioxidant capacity was measured by 1,1-diphenyl-2-picrylhydrazyl assay. To solve the optimization problem formulated, an artificial neural network was developed. The resolution of the optimization problem allowed the establishment of the optimal operating conditions of the process, maximizing the antioxidant capacity values depending on the characteristics of the process. Results showed that the best operating conditions to maximize the antioxidant capacity of mangosteen peels were a drying temperature of 70℃ and using high-power ultrasound as extraction method.

Effects of photobiomodulation on cellular viability and cancer stem cell phenotype in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy; it has been shown that cancer stem cells (CSC) are present in OSCC and associated with tumor growth, invasion, metastasis, and therapeutic resistance. Photobiomodulation (PBM) is an alternative tool for oncologic treatment adverse effects such as oral mucositis (OM); however, controversy exists regarding the undesirable effects of PBM on tumor or CSC. This study aimed to evaluate in vitro, the effects of PBM, with the same dosimetric parameters as those used in the clinic for OM prevention and treatment, on OSCC cellular viability, as well as PBM's effect on CSC properties and its phenotype. OSCC cell lines were submitted to single or daily PBM with 3 J/cm2 and 6 J/cm2 and then the cellular viability was evaluated by MTT, NRU (neutral red uptake), and CVS (crystal violet staining). The CSC populations were evaluated by clonogenic formation assay, flow cytometry, and RT-qPCR. The single PBM with the 3 J/cm2 group was associated with increased cellular viability. Daily PBM with 3 J/cm2 and 6 J/cm2 was associated with a significant decrease in cellular viability. Additionally, daily PBM was not able to promote CSC self-renewal or the CD44high/ESAlow and CD44high/ESAhigh cellular phenotypes. Moreover, a decrease in the number of spheres and in the expression of the CSC related gene BMI1 was observed after daily PBM with 6 J/cm2. Daily PBM with 3 J/cm2 and 6 J/cm2 showed an inhibitory effect on cellular viability and was not able to promote the CSC self-renewal or phenotype.

Discovery of EST73502, a Dual µ-Opioid Receptor Agonist and σ1 Receptor Antagonist Clinical Candidate for the Treatment of Pain.

The synthesis and pharmacological activity of a new series of 4-alkyl-1-oxa-4,9-diazaspiro[5.5]undecane derivatives as potent dual ligands for the σ1 receptor (σ1R) and the µ-opioid receptor (MOR) are reported. A lead optimization program over the initial 4-aryl analogues provided 4-alkyl derivatives with the desired functionality and good selectivity and ADME profiles. Compound 14u (EST73502) showed MOR agonism and σ1R antagonism and a potent analgesic activity, comparable to the MOR agonist oxycodone in animal models of acute and chronic pain after single and repeated administration. Contrary to oxycodone, 14u produces analgesic activity with reduced opioid-induced relevant adverse events, like intestinal transit inhibition and naloxone-precipitated behavioral signs of opiate withdrawal. These results provide evidence that dual MOR agonism and σ1R antagonism may be a useful strategy for obtaining potent and safer analgesics and were the basis for the selection of 14u as a clinical candidate for the treatment of pain.

Photobiomodulation is associated with a decrease in cell viability and migration in oral squamous cell carcinoma.

The treatment of squamous cell carcinoma (SCC) involves surgery, chemotherapy, and/or radiotherapy, which can cause mucositis (inflammation of the oral mucosa that causes considerable pain and can compromise the continuity of oncological treatment). Photobiomodulation (PBM) has been successfully used in the treatment of mucositis, but doubts arise regarding the use of laser for areas in which tumor cells may remain. In this study, the effect of PBM on the viability, mitochondrial activity, proliferation, apoptosis, and migration of cells derived from oral SCC was evaluated. SCC9 cells were irradiated with laser (660 and 780 nm, using 11 dosimetric parameters) and submitted to mitochondrial and caspase 3 activity tests after 1 and 3 days. Based on the results, cell viability (neutral red assay), proliferation (BrdU assay), and migration (scratch-wound assay) were evaluated using only the dosimetric parameters recommended for mucositis. Non-irradiated cells served as the control. The experiments were performed in triplicate. The 11 parameters diminished mitochondrial activity and induced tumor cell apoptosis. Using the parameters recommended for mucositis, irradiation with 780 nm (70 mW, 4 J/cm2) proved to be the safest and led to a reduction in cell viability, the induction of apoptosis, and a reduction in the migration capacity of the tumor cells.

Rifamycin SV-MMX® for treatment of travellers' diarrhea: equally effective as ciprofloxacin and not associated with the acquisition of multi-drug resistant bacteria.

Background: The novel oral antibiotic formulation Rifamycin SV-MMX®, with a targeted delivery to the distal small bowel and colon, was superior to placebo in treating travellers' diarrhea (TD) in a previous study. Thus, a study was designed to compare this poorly absorbed antibiotic with the systemic agent ciprofloxacin. Methods: In a randomized double-blind phase 3 study (ERASE), the efficacy and safety of Rifamycin SV-MMX® 400 mg twice daily (RIF-MMX) was compared with ciprofloxacin 500 mg twice daily in the oral treatment of TD. Overall, 835 international visitors to India, Guatemala or Ecuador with acute TD were randomized to receive a 3-day treatment with RIF-MMX (n = 420) or ciprofloxacin (n = 415). Primary endpoint was time to last unformed stool (TLUS), after which clinical cure was declared. Stools samples for microbiological evaluation were collected at the baseline visit and the end of treatment visit. Results: Median TLUS in the RIF-MMX group was 42.8 h versus 36.8 h in the ciprofloxacin group indicating non-inferiority of RIF-MMX to ciprofloxacin (P = 0.0035). Secondary efficacy endpoint results including clinical cure rate, treatment failure rate, requirement of rescue therapy as well as microbiological eradication rate confirmed those of the primary analysis indicating equal efficacy for both compounds. While patients receiving ciprofloxacin showed a significant increase of Extended Spectrum Beta Lactamase Producing-Escherichia coli (ESBL-E. Coli) colonization rates after 3-days treatment (6.9%), rates did not increase in patients receiving RIF-MMX (-0.3%). Both drugs were well-tolerated and safe. Conclusion: The novel multi-matrix formulation of the broad-spectrum, poorly absorbed antibiotic Rifamycin SV was found non-inferior to the systemic antibiotic ciprofloxacin in the oral treatment of non-dysenteric TD with the advantage of a lower risk of ESBL-E. Coli acquisition.

Photobiomodulation and different macrophages phenotypes during muscle tissue repair.

Macrophages play a very important role in the conduction of several regenerative processes mainly due to their plasticity and multiple functions. In the muscle repair process, while M1 macrophages regulate the inflammatory and proliferative phases, M2 (anti-inflammatory) macrophages direct the differentiation and remodelling phases, leading to tissue regeneration. The aim of this study was to evaluate the effect of red and near infrared (NIR) photobiomodulation (PBM) on macrophage phenotypes and correlate these findings with the repair process following acute muscle injury. Wistar rats were divided into 4 groups: control; muscle injury; muscle injury + red PBM; and muscle injury + NIR PBM. After 2, 4 and 7 days, the tibialis anterior muscle was processed for analysis. Macrophages phenotypic profile was evaluated by immunohistochemistry and correlated with the different stages of the skeletal muscle repair by the qualitative and quantitative morphological analysis as well as by the evaluation of IL-6, TNF-α and TGF-ß mRNA expression. Photobiomodulation at both wavelengths was able to decrease the number of CD68+ (M1) macrophages 2 days after muscle injury and increase the number of CD163+ (M2) macrophages 7 days after injury. However, only NIR treatment was able to increase the number of CD206+ M2 macrophages (Day 2) and TGF-ß mRNA expression (Day 2, 4 and 7), favouring the repair process more expressivelly. Treatment with PBM was able to modulate the inflammation phase, optimize the transition from the inflammatory to the regeneration phase (mainly with NIR light) and improve the final step of regeneration, enhancing tissue repair.

Image-guided thermal therapy with a dual-contrast magnetic nanoparticle formulation: A feasibility study.

PURPOSE/OBJECTIVE: The aim of this study was to develop and investigate the properties of a magnetic iron oxide nanoparticle-ethiodised oil formulation for image-guided thermal therapy of liver cancer. MATERIALS AND METHODS: The formulation comprises bionised nano-ferrite (BNF) nanoparticles suspended in ethiodised oil, emulsified with polysorbate 20 (BNF-lip). Nanoparticle size was measured via photon correlation spectroscopy and transmission electron microscopy. In vivo thermal therapy capability was tested in two groups of male Foxn1(nu) mice bearing subcutaneous HepG2 xenograft tumours. Group I (n = 12) was used to screen conditions for group II (n = 48). In group II, mice received one of BNF-lip (n = 18), BNF alone (n = 16), or PBS (n = 14), followed by alternating magnetic field (AMF) hyperthermia, with either varied duration (15 or 20 min) or amplitude (0, 16, 20, or 24 kA/m). Image-guided fluoroscopic intra-arterial injection of BNF-lip was tested in New Zealand white rabbits (n = 10), bearing liver VX2 tumours. The animals were subsequently imaged with CT and 3 T MRI, up to 7 days post-injection. The tumours were histopathologically evaluated for distribution of BNF-lip. RESULTS: The BNF showed larger aggregate diameters when suspended in BNF-lip, compared to clear solution. The BNF-lip formulation produced maximum tumour temperatures with AMF >20 kA/m and showed positive X-ray visibility and substantial shortening of T1 and T2 relaxation time, with sustained intratumoural retention up to 7 days post-injection. On pathology, intratumoural BNF-lip distribution correlated well with CT imaging of intratumoural BNF-lip distribution. CONCLUSION: The BNF-lip formulation has favourable thermal and dual imaging capabilities for image-guided thermal therapy of liver cancer, suggesting further exploration for clinical applications.

Photomodulation of the osteoclastogenic potential of oral squamous carcinoma cells.

The treatment for oral cancer usually involves surgical excision followed by chemotherapy and/or radiotherapy. The combination of these therapies generally promotes a serious inflammation of the mucosa of the digestive tract, denominated mucositis, which compromises continuity of treatment. Photobiomodulation (PBM) therapy has been used successfully to reduce the oral mucositis, however there is still some controversy regarding the effects of this therapy on unintentionally irradiated tumor cells that may remain after cancer treatment. The aim of this study was to analyze the effect of PBM therapy (using parameters for mucositis) on the modulation of osteoclastogenic potential of a cell line derived from human lingual squamous cell carcinoma (SCC9). Previously irradiated SCC9 cells were co-cultured with human osteoclast precursors. Co-cultures performed with non-irradiated SCC9 cells served as control. After 7, 14 and 21 days the co-cultures were evaluated for the tartrate-resistant acid phosphatase (TRAP) activity, an osteoclastogenic marker. Additionally, the monocultures of SCC9 cells (non-irradiated and irradiated) were analyzed for cell viability/proliferation and for the expression of IL-11 and PTHrP. The irradiation of SCC9 cells with PBM with an energy density of 4 J/cm2 decreased the pro-osteoclastogenic potential of those cells. This may represent a potential useful side effect of PBM therapy. PBM (using recommended parameters for mucositis treatment) decreases the osteoclastogenic potential of oral squamous carcinoma cells.

[Effectiveness of physiotherapy on painful shoulder impingement syndrome]. / Efectividad de los medios físicos en el síndrome de abducción dolorosa de hombro.

BACKGROUND: Painful shoulder impingement syndrome is one of the first reasons for care in rehabilitation centres. As the evidence regarding the effectiveness of physical measures as adjuvant treatment is limited, the aim of this study was to determine the effectiveness of physiotherapy on shoulder pain. MATERIAL AND METHODS: A retrospective and analytical study was conducted using the medical records of patients with shoulder pain who attended in a rehabilitation centre from October 2010 to September 2011. The demographic and clinical data were collected, and the clinical improvement was determined as: complete, incomplete, or no improvement. STATISTICAL ANALYSIS: Chi squared was used to determine whether there were differences between the different modalities of physiotherapy, as well as the level of improvement. RESULTS: The study included a total of 181 patients, with a mean age of 54.3 years, and a mean of 4.6 months of onset of pain. The physiotherapy treatments included: warm compresses plus interferential current (60.2%), and warm compresses plus ultrasound (17.1%). Just over half (53.6%) obtained a moderate recovery, 36.4% slight improvement, and 9.9% no improvement. No significant differences were found between the different forms of therapy. CONCLUSIONS: The supervised rehabilitation program consists of 9 sessions of physiotherapy. A functional improvement of 90% was obtained, without finding any statistical differences between the therapies used.

Aluminium-phthalocyanine chloride nanoemulsions for anticancer photodynamic therapy: Development and in vitro activity against monolayers and spheroids of human mammary adenocarcinoma MCF-7 cells.

BACKGROUND: Photodynamic therapy (PDT) combines light, molecular oxygen and a photosensitizer to induce oxidative stress in target cells. Certain hydrophobic photosensitizers, such as aluminium-phthalocyanine chloride (AlPc), have significant potential for antitumor PDT applications. However, hydrophobic molecules often require drug-delivery systems, such as nanostructures, to improve their pharmacokinetic properties and to prevent aggregation, which has a quenching effect on the photoemission properties in aqueous media. As a result, this work aims to develop and test the efficacy of an AlPc in the form of a nanoemulsion to enable its use in anticancer PDT. RESULTS: The nanoemulsion was developed using castor oil and Cremophor ELP®, and a monodisperse population of nanodroplets with a hydrodynamic diameter of approximately 25 nm was obtained. While free AlPc failed to show significant activity against human breast adenocarcinoma MCF-7 cells in an in vitro PDT assay, the AlPc in the nanoemulsion showed intense photodynamic activity. Photoactivated AlPc exhibited a 50 % cytotoxicity concentration (CC50) of 6.0 nM when applied to MCF-7 cell monolayers and exerted a powerful cytotoxic effect on MCF-7 cell spheroids. CONCLUSION: Through the use of spontaneous emulsification, a stable AlPc nanoemulsion was developed that exhibits strong in vitro photodynamic activity on cancer cells.

Highly focalised thermotherapy using a ferrimagnetic cement in the treatment of a melanoma mouse model by low temperature hyperthermia.

PURPOSE: Evaluation of the effectiveness of highly focalised thermotherapy (HFT) in a melanoma mouse model, using a ferrimagnetic cement (FC) and repeated low hyperthermia treatments. MATERIALS AND METHODS: A melanoma mouse model was induced with B16F10 cells in C57BL6 mice. The FC, injected into the tumour, was used as the magnetic vehicle for HFT. FC location within the tumour was assessed by radiography and its capability to generate heat, when exposed to an external high frequency magnetic field (HFMF), monitored by thermal camera. The HFT treatment consisted of three HFMF exposures, with 48-h intervals, each one lasting 30 min, with a 5-6°C tumour temperature increase. At the end of the experiment, FC samples were characterised by scanning electron microscopy (SEM) and energy dispersion spectroscopy (EDS). The presence of iron contents was analysed in the tumour, lungs, liver and spleen. Histological evaluation and immunohistochemical staining for caspase-3 were performed. Tumour growth was monitored during the experiment. RESULTS: Surface analysis showed FC stabilisation within the tumour, and iron was absent. The thermal camera confirmed the localised temperature increase in the tumour. HFT treatments inhibited the tumour growth by ∼70% compared to controls. This was due to cell destruction by necrosis and apoptosis. CONCLUSIONS: The HFT, using the FC, proved to be a minimally invasive technique that statistically inhibited tumour growth. Results suggested that this methodology seems to be a promising technique for the treatment of solid tumours, allowing repeated low hyperthermia treatments, which can be easier and less traumatic than other hyperthermia techniques.

Acute and long-term effects of hyperthermia in B16-F10 melanoma cells.

OBJECTIVE: Hyperthermia uses exogenous heat induction as a cancer therapy. This work addresses the acute and long-term effects of hyperthermia in the highly metastatic melanoma cell line B16-F10. MATERIALS AND METHODS: Melanoma cells were submitted to one heat treatment, 45°C for 30 min, and thereafter were kept at 37°C for an additional period of 14 days. Cultures maintained at 37°C were used as control. Cultures were assessed for the heat shock reaction. RESULTS: Immediately after the heat shock, cells began a process of fast degradation, and, in the first 24 h, cultures showed decreased viability, alterations in cell morphology and F-actin cytoskeleton organization, significant reduction in the number of adherent cells, most of them in a process of late apoptosis, and an altered gene expression profile. A follow-up of two weeks after heat exposure showed that viability and number of adherent cells remained very low, with a high percentage of early apoptotic cells. Still, heat-treated cultures maintained a low but relatively constant population of cells in S and G(2)/M phases for a long period after heat exposure, evidencing the presence of metabolically active cells. CONCLUSION: The melanoma cell line B16-F10 is susceptible to one hyperthermia treatment at 45°C, with significant induced acute and long-term effects. However, a low but apparently stable percentage of metabolically active cells survived long after heat exposure.