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1.
Hernia ; 28(3): 723-743, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38625435

ABSTRACT

INTRODUCTION: Parastomal hernia (PSH) is the most common and challenging complication after stoma creation, with an estimated 50% incidence 2 years after the index surgery. Mesh repair is the treatment of choice. Laparoscopic and/or robotic approaches allow acceptable outcomes. MATERIALS AND METHODS: A systematic literature review from January 2012 to November 2023 was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Embase, PubMed, and Scopus search were performed to select articles dealing with minimally invasive surgical treatment for PSH after end colostomy. RESULTS: 603 studies were found, and 24 were chosen. When compared to open surgery, laparoscopy showed decreased postoperative complications and recurrence. The main laparoscopic approaches are the keyhole (KH), the Sugarbaker (SB), and the sandwich technique. Continuous improvement in surgery, mesh technology, and surgeons' expertise led to an amelioration of surgical outcome and recurrence rate after repair. Recent studies showed comparable outcomes for SB and KH techniques, while novel surgical approaches have been proposed in an attempt to further increase the operative and long-term results. Reports on PSH robotic repairs are scarce and describe small series results, suggesting a role of the initial learning curve as a risk factor for complications. CONCLUSION: End-colostomy PSH surgical repair still represents a challenge for surgeons. Recent evidence has not shown a significant advantage in postoperative complications and recurrence with a specific repair among SB, KH, and sandwich technique. The paucity of data on robotic surgery does not allow to draw definitive conclusion. Further primary, multicentric, and larger cohort studies are needed.


Subject(s)
Colostomy , Herniorrhaphy , Laparoscopy , Robotic Surgical Procedures , Humans , Robotic Surgical Procedures/adverse effects , Laparoscopy/adverse effects , Herniorrhaphy/methods , Herniorrhaphy/adverse effects , Colostomy/adverse effects , Incisional Hernia/surgery , Incisional Hernia/etiology , Hernia, Ventral/surgery , Hernia, Ventral/etiology , Surgical Mesh/adverse effects , Postoperative Complications/etiology , Surgical Stomas/adverse effects
2.
Antimicrob Agents Chemother ; 68(5): e0091523, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38517190

ABSTRACT

Primaquine is the mainstream antimalarial drug to prevent Plasmodium vivax relapses. However, this drug can induce hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency. Nanostructure formulations of primaquine loaded with D-galactose were used as a strategy to target the drug to the liver and decrease the hemolytic risks. Nanoemulsion (NE-Pq) and nanochitosan (NQ-Pq) formulations of primaquine diphosphate containing D-galactose were prepared and characterized by their physicochemistry properties. Pharmacokinetic and biodistribution studies were conducted using Swiss Webster mice. A single dose of 10 mg/kg of each nanoformulation or free primaquine solution was administered by gavage to the animals, which were killed at 0.5, 1, 2, 4, 8, and 24 hours. Blood samples and tissues were collected, processed, and analyzed by high-performance liquid chromatography. The nanoformulation showed sizes around 200 nm (NE-Pq) and 400 nm (NQ-Pq) and physicochemical stability for over 30 days. Free primaquine solution achieved higher primaquine Cmax in the liver than NE-Pq or NQ-Pq at 0.5 hours. However, the half-life and mean residence time (MRT) of primaquine in the liver were three times higher with the NQ-Pq formulation than with free primaquine, and the volume distribution was four times higher. Conversely, primaquine's half-life, MRT, and volume distribution in the plasma were lower for NQ-Pq than for free primaquine. NE-Pq, on the other hand, accumulated more in the lungs but not in the liver. Galactose-coated primaquine nanochitosan formulation showed increased drug targeting to the liver compared to free primaquine and may represent a promising strategy for a more efficient and safer radical cure for vivax malaria.


Subject(s)
Antimalarials , Chitosan , Galactose , Liver , Primaquine , Primaquine/pharmacokinetics , Primaquine/chemistry , Animals , Mice , Liver/metabolism , Liver/drug effects , Galactose/chemistry , Chitosan/chemistry , Antimalarials/pharmacokinetics , Nanoparticles/chemistry , Tissue Distribution , Nanostructures/chemistry , Male
3.
Photodiagnosis Photodyn Ther ; 32: 102045, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33011398

ABSTRACT

Cervical cancer is a serious worldwide health problem. In view of the potentially harmful effects of current conventional therapies, photodynamic therapy may be an option as it is a minimally invasive therapy and can promote selective cytotoxic activity for neoplastic cells in the target tissue., Berberine (BBR) as an isolated molecule is a natural compound that has antineoplastic properties and potential action as a photosensitizer agent. The purpose of this study was to evaluate the use of berberine as a photosensitizer in photodynamic therapy (PDT) protocols and observe the effects produced by this association in cervical carcinoma cells and in immortalized keratinocytes. Incubation with 2.5 µM berberine promoted less than 10 % of cellular death in both cell lines studied. In addition, by fluorescence microscopy, we demonstrated that berberine was internalized by the cells, and after a period of 48 h, it was still present in the intracellular environment preferentially localized in the cytoplasm. After photodynamic therapy using berberine as a photosensitizer and visible light activation at 447 (±10) nm, we observed a phototoxic effect, which resulted in 19.84 % cell viability for Caski cells and 47.22 % cell viability for HaCaT. Treatment with berberine associated with photodynamic therapy promoted an increase in the production of reactive species of oxygen (ROS) and caspase-3 activity, indicating a preferential cell death mechanism by caspase-dependent apoptosis. Therefore, we demonstrated that berberine is an efficient photosensitizer and that its association with photodynamic therapy may be a potential anticancer treatment strategy for cervical cancer.


Subject(s)
Berberine , Photochemotherapy , Uterine Cervical Neoplasms , Apoptosis/drug effects , Berberine/pharmacology , Cell Line , Cell Line, Tumor , Cell Survival/drug effects , Female , Humans , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Reactive Oxygen Species , Uterine Cervical Neoplasms/therapy
4.
Oral Dis ; 22(5): 415-22, 2016 Jul.
Article in English | MEDLINE | ID: mdl-26914185

ABSTRACT

This study evaluated the photoinactivation of Candida albicans in a murine model of oral candidiasis using chloro-aluminum phthalocyanine (ClAlP) encapsulated in cationic nanoemulsions (NE) and chloro-aluminum phthalocyanine (ClAlP) diluted in DMSO (DMSO) as photosensitizer (PS). Seventy-five 6-week-old female Swiss mice were immunosuppressed and inoculated with C. albicans to induce oral candidiasis. PDT was performed on the tongue by the application of the photosensitizers and LED light (100 J cm(-2) -660 nm). Twenty-four hours and 7 days after treatments, microbiological evaluation was carried out by recovering C. albicans from the tongue of animals (CFU ml(-1) ). Then, mice were sacrificed and the tongues were surgically removed for histological and biomolecular analysis of pro- and anti-inflammatory cytokines. Data were analyzed by ANOVA followed by Tukey's post hoc test. ClAlP-NE-mediated PDT reduced 2.26 log10 of C. albicans recovered from the tongue when compared with the control group (P-L-) (P < 0.05). PDT did not promote adverse effects on the tongue tissue. Seven days after treatment, all animals were completely healthy. In summary, PDT mediated by chloro-aluminum phthalocyanine entrapped in cationic nanoemulsions was effective in reducing C. albicans recovered from the oral lesions of immunocompromised mice.


Subject(s)
Candida albicans/drug effects , Candida albicans/radiation effects , Candidiasis, Oral/drug therapy , Indoles/pharmacology , Organometallic Compounds/pharmacology , Photochemotherapy/methods , Animals , Candida albicans/isolation & purification , Candidiasis, Oral/microbiology , Cytokines/analysis , Cytokines/genetics , Disease Models, Animal , Female , Mice , Photosensitizing Agents/pharmacology , Random Allocation , Tetracycline/pharmacology , Tongue/drug effects , Tongue/microbiology , Tongue/radiation effects
5.
Eur J Med Chem ; 95: 267-76, 2015 May 05.
Article in English | MEDLINE | ID: mdl-25827397

ABSTRACT

The development of biocompatible polymeric nanoparticles has become an important strategy for optimizing the therapeutic efficacy of many classical drugs, as it may expand their activities, reduce their toxicity, increase their bioactivity and improve biodistribution. In this study, nanoparticles of Amphotericin B entrapped within poly (lactic-co-glycolic) acid and incorporated with dimercaptosuccinic acid (NANO-D-AMB) as a target molecule were evaluated for their physic-chemical characteristics, pharmacokinetics, biocompatibility and antifungal activity. We found high plasma concentrations of Amphotericin B upon treatment with NANO-D-AMB and a high uptake of nanoparticles in the lungs, liver and spleen. NANO-D-AMB exhibited antifungal efficacy against Paracoccidioides brasiliensis and induced much lower cytotoxicity levels compared to D-AMB formulation in vivo and in vitro. Together, these results confirm that NANO-D-AMB improves Amphotericin B delivery and suggest this delivery system as a potential alternative to the use of Amphotericin B sodium deoxycholate.


Subject(s)
Amphotericin B/chemistry , Amphotericin B/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Deoxycholic Acid/chemistry , Deoxycholic Acid/pharmacology , Drug Carriers/chemistry , Lactic Acid/chemistry , Nanoparticles/chemistry , Polyglycolic Acid/chemistry , Amphotericin B/adverse effects , Amphotericin B/therapeutic use , Animals , Antifungal Agents/adverse effects , Antifungal Agents/therapeutic use , Deoxycholic Acid/adverse effects , Deoxycholic Acid/therapeutic use , Drug Carriers/pharmacokinetics , Drug Combinations , Drug Liberation , Lactic Acid/pharmacokinetics , Materials Testing , Mice , Paracoccidioides/drug effects , Paracoccidioides/physiology , Paracoccidioidomycosis/drug therapy , Polyglycolic Acid/pharmacokinetics , Polylactic Acid-Polyglycolic Acid Copolymer , Safety , Succimer/chemistry , Tissue Distribution
6.
Curr Med Chem ; 20(14): 1904-11, 2013.
Article in English | MEDLINE | ID: mdl-23409713

ABSTRACT

For some time Photodynamic Therapy and electrochemotherapy have been used as alternative therapies against skin cancer. The primary aim of this work was to develop, characterize, and evaluate the in vitro cytotoxic activity of new drug delivery systems based on chitosan nanoparticles containing aminolevulinic acid derivatives such as prodrug (5-ALA and its ester derivative 8-ALA). The second goal of this study was to evaluate the synergistic effect of a combination of classical Photodynamic Therapy and electrochemotherapy, which is routinely utilized to modulate and enhance the permeation of photosensitizers, prodrugs, and other active compounds through the skin, improving the efficiency of PDT in the treatment of cutaneous neoplasms.


Subject(s)
Aminolevulinic Acid/analogs & derivatives , Aminolevulinic Acid/administration & dosage , Chitosan/administration & dosage , Drug Delivery Systems/methods , Electrochemotherapy/methods , Melanoma/drug therapy , Nanoparticles/administration & dosage , Photochemotherapy/methods , Humans
7.
Curr Med Chem ; 19(30): 5157-63, 2012.
Article in English | MEDLINE | ID: mdl-22934760

ABSTRACT

This research evaluated the effect of multiple-wave lasertherapy on the healing process of surgical wounds based on in vitro models denominated stem-dermal equivalents. These human skin models were obtained from a co-culture of dermal cells and bone marrow mesenchymal stem cells. The experimental tests were carried out using a LED portable to multiple waves (operating at 660 nm and 810 nm) at different doses to induce photobiostimulation (10 to 70 mJ.cm-2). Moreover, a photosensitizer drug was employed as a new advanced designed nanomaterial, being a nanoemulsion with biopolymers to obtain an efficient drug delivery system to release lipophilic compounds. The studies were performed considering the light combination application monitoring the kinetic contraction of the dermal equivalent model and the quantification of important macromolecules (as metaloproteases derivatives), related directly with wound healing process. Results showed that an appropriate photomodulation using the combination of both wavelengths (in the red and infrared range) is possible, such that it can contribute to wound healing therapy and/or other pathological skin disease treatment.


Subject(s)
Indoles/administration & dosage , Light , Organometallic Compounds/administration & dosage , Photosensitizing Agents/administration & dosage , Wound Healing/drug effects , Wound Healing/radiation effects , Cells, Cultured , Coculture Techniques , Emulsions , Fibroblasts , Gingiva/cytology , Humans , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Mesenchymal Stem Cells , Nanostructures , Photochemotherapy
8.
J Nanosci Nanotechnol ; 12(6): 5111-6, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22905587

ABSTRACT

Loaded microspheres with a silicon (IV) phthalocyanine derivative (NzPC) acting as a photosensitizer were prepared from polyhydroxybutyrate-co-valerate (PHBHV) and poly(ecaprolactone) (PCL) polymers using the emulsification solvent evaporation method (EE). The aim of our study was to prepare two systems of these biodegradable PHBHV/PCL microspheres. The first one containing only photosensitizer previously incorporated in the PHBHV and poly(ecaprolactone) (PCL) microspheres and the second one with the post magnetization of the DDS with magnetic nanoparticles. Magnetic fluid is successfully used for controlled incorporation of nanosized magnetic particles within the micron-sized template. This is the first time that we could get a successful pos incorporation of nanosized magnetic particles in a previously-prepared polymeric template. This procedure opens a great number of possibilities of post-functionalization of polymeric micro or nanoparticles with different bioactive materials. The NzPC release profile of the systems is ideal for PDT, the zeta potential and the size particle are stable upon aging in time. In vitro studies were evaluated using gingival fibroblastic cell line. The dark citotoxicity, the phototoxicity and the AC magnetic field assays of the as-prepared nanomagnetic composite were evaluated and the cellular viability analyzed by the classical test of MTT.


Subject(s)
Fibroblasts/physiology , Hyperthermia, Induced/methods , Indoles/administration & dosage , Nanocapsules/administration & dosage , Nanocapsules/chemistry , Photochemotherapy/methods , Biocompatible Materials , Cell Line , Fibroblasts/cytology , Humans , Isoindoles , Magnetic Fields , Microspheres , Photosensitizing Agents
9.
Lasers Med Sci ; 27(6): 1205-12, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22278349

ABSTRACT

The biofilms formed by opportunistic yeasts serve as a persistent reservoir of infection and impair the treatment of fungal diseases. The aim of this study was to evaluate photodynamic inactivation (PDI) of biofilms formed by Candida spp. and the emerging pathogens Trichosporon mucoides and Kodamaea ohmeri by a cationic nanoemulsion of zinc 2,9,16,23-tetrakis(phenylthio)-29H,31H-phthalocyanine (ZnPc). Biofilms formed by yeasts after 48 h in the bottom of 96-well microtiter plates were treated with the photosensitizer (ZnPc) and a GaAlAs laser (26.3 J cm(-2)). The biofilm cells were scraped off the well wall, homogenized, and seeded onto Sabouraud dextrose agar plates that were then incubated at 37°C for 48 h. Efficient PDI of biofilms was verified by counting colony-forming units (CFU/ml), and the data were submitted to analysis of variance and the Tukey test (p < 0.05). All biofilms studied were susceptible to PDI with statistically significant differences. The strains of Candida genus were more resistant to PDI than emerging pathogens T. mucoides and K. ohmeri. A mean reduction of 0.45 log was achieved for Candida spp. biofilms, and a reduction of 0.85 and 0.84, were achieved for biofilms formed by T. mucoides and K. ohmeri, respectively. Therefore, PDI by treatment with nanostructured formulations cationic zinc 2,9,16,23- tetrakis (phenylthio)- 29H, 31H- phthalocyanine (ZnPc) and a laser reduced the number of cells in the biofilms formed by strains of C. albicans and non-Candida albicans as well the emerging pathogens T. mucoides and K. ohmeri.


Subject(s)
Antifungal Agents/pharmacology , Candida/drug effects , Indoles/pharmacology , Lasers , Organometallic Compounds/pharmacology , Saccharomycetales/drug effects , Trichosporon/drug effects , Biofilms/drug effects , Candida/physiology , Colony Count, Microbial , Emulsions/pharmacology , Humans , Mouth Mucosa/microbiology , Nanostructures , Photochemotherapy , Photosensitizing Agents/pharmacology , Saccharomycetales/physiology , Trichosporon/physiology
10.
Platelets ; 23(6): 439-46, 2012.
Article in English | MEDLINE | ID: mdl-22150374

ABSTRACT

UNLABELLED: Patients with type 2 diabetes mellitus exhibit considerable platelet dysfunction, though this is poorly characterized in patients with diabetes taking aspirin for the primary prevention of cardiovascular events. We sought to compare platelet function in this patient population with that of a high-risk group of non-diabetic subjects with a history of previous myocardial infarction (MI), and to assess whether glycaemic control impacts on platelet function. METHODS: Platelet aggregation was measured in response to incremental concentrations of five platelet agonists using light transmission aggregometry. All patients were taking aspirin, and aspirin insensitivity was defined as ≥ 20% arachidonic acid (AA) mediated aggregation. Patients with diabetes were divided according to glycaemic control (HbA(1c)): optimal ≤ 6.5, good 6.6-7.4 and suboptimal ≥ 7.5%. RESULTS: In total, 85 patients with type 2 diabetes and 35 non-diabetic patients with previous MI were recruited. Compared to MI patients, diabetes patients had increased aggregation in response to multiple concentrations of epinephrine, collagen, adenosine diphosphate and AA. Aspirin insensitivity was more common in type 2 diabetes (15% vs. 0%, p=0.037). Platelet aggregation was increased in response to several agonists patients with suboptimal glycaemic control compared to patients with optimal control. Aspirin insensitivity was also more common in patients with suboptimal glycaemic control compared to those with good or optimal control (26.0% vs. 8.3% vs. 4%, p=0.04). CONCLUSION: Patients with type 2 diabetes mellitus, without proven vascular disease, exhibit platelet dysfunction and have increased platelet aggregation and aspirin insensitivity compared to non-diabetic patients with previous MI. Platelet dysfunction in diabetes is more severe in patients with suboptimal glycaemic control.


Subject(s)
Aspirin/administration & dosage , Diabetes Mellitus, Type 2/pathology , Glycated Hemoglobin/analysis , Myocardial Infarction/pathology , Platelet Aggregation/drug effects , Adenosine Diphosphate/pharmacology , Adolescent , Adult , Aged , Aged, 80 and over , Arachidonic Acid/pharmacology , Blood Glucose/analysis , Blood Platelets/drug effects , Collagen/pharmacology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Epinephrine/pharmacology , Female , Humans , Male , Middle Aged , Myocardial Infarction/drug therapy , Myocardial Infarction/metabolism , Severity of Illness Index , Survivors
11.
Rev Neurol (Paris) ; 168(2): 161-9, 2012 Feb.
Article in French | MEDLINE | ID: mdl-22104064

ABSTRACT

OBJECTIVE: The aim of the study was to compare the profiles of patients with young (age≤65 years) and late (age>65 years) onset of dementia in a memory clinic of a Memory Referral Center in Lyons (France), for the year 2008. METHODS: A total of 746 demented patients were evaluated using clinical, neuropsychological and imaging information. For each patient, diagnoses of the dementing disorder used clinical criteria at the first visit. We examined the distribution of patients diagnosis and differences in sex and education between the young-onset dementia (YOD) and the late-onset dementia (LOD) groups. RESULTS: From a total of 746 registered demented patients (300 men, 446 women), there were 91 patients (12.2%) with YOD (from 36.5 to 65 years) and 655 patients with LOD (from 66 to 92 years). Among the 91 YOD patients, the most frequent causes were Mild Cognitive Impairment (MCI) (18.7%), then Alzheimer's disease (AD), frontotemporal dementia and posterior cortical atrophy (14.3% each), followed by progressive aphasia (11.0%), dementia with Lewy bodies (DLD) (9.9%), semantic dementia (8.8%), other causes (3.3%), vascular dementia (2.2%), undetermined dementia (2.2%), AD+cerebrovascular disease (1.1%). Among the 655 LOD patients, AD was the most frequent cause of dementia (57.4%). Referred cases by a specialist doctor were 50.5% in the YOD group and 12.7% in the LOD group (P<0.0001). In the ACP group, 68.4% patients began before 65 years. CONCLUSION: The number of YOD in our memory clinic was four-fold the number of expected patients in France. The characteristics of the Referral Center explain the high frequency of rare dementia such as progressive aphasia (5.2% of overall number), semantic dementia (3.6%) and posterior cortical atrophy (2.5%).


Subject(s)
Dementia/diagnosis , Dementia/epidemiology , Dementia/etiology , Referral and Consultation/statistics & numerical data , Adult , Age of Onset , Aged , Ambulatory Care Facilities/organization & administration , Dementia/classification , Female , France/epidemiology , Humans , Male , Memory Disorders/diagnosis , Middle Aged , Neurology/methods , Neurology/organization & administration , Neurology/statistics & numerical data , Retrospective Studies , Socioeconomic Factors
12.
Curr Med Chem ; 18(22): 3376-81, 2011.
Article in English | MEDLINE | ID: mdl-21728963

ABSTRACT

Nanotechnology and tissue engineering are promising scientific fields in the development of advanced materials useful to human health. This article describes the preparation of a nanocarrier for the controlled release of a photosensitizer compound associated with low-level light therapy for skin wound healing treatment and applicable to other skin diseases. A biological model was used as an in vitro skin equivalent based on a three-dimensional culture of fibroblasts and mesenchymal stem cells and denominated by dermal equivalent (DE). Results show that it is possible to use the photomodulation process to control the wound healing in a scratching process and to induce the biomolecules release, both of which are related with the inflammatory wound healing process. In the studies, the MMP-2 and MMP-9 expression from zymography analyses were evaluated. All results showed a dependence on enzymatic activity relating to lowlevel laser applications which indicates a potential application in wound healing processes based on phototherapy and nanotechnology.


Subject(s)
Indoles/pharmacology , Low-Level Light Therapy/methods , Mesenchymal Stem Cells/radiation effects , Organometallic Compounds/pharmacology , Photochemotherapy/methods , Skin/radiation effects , Bone Marrow Cells , Coculture Techniques , Emulsions , Fibroblasts/cytology , Humans , Indoles/therapeutic use , Matrix Metalloproteinase 2 , Matrix Metalloproteinase 9 , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Nanotechnology , Organometallic Compounds/therapeutic use , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Skin/drug effects , Wound Healing/drug effects , Wound Healing/radiation effects
13.
Curr Eye Res ; 36(9): 857-9, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21599469

ABSTRACT

PURPOSE: To describe the presence of iris neovascularization in a rabbit-model of retinal neovascularization induced by the intravitreal injection of latex-derived angiogenic fraction microspheres (LAF). MATERIALS AND METHODS: Eight New Zealand rabbits received one intravitreal injection of PLGA (L-lactide-co-glycolide) microspheres with 50 ug of LAF in the right eye (Group A). Microspheres without the LAF (0.1 ml) were injected in controls (Group B; n = 8). Follow-up with clinical evaluation and iris fluorescein angiography was performed after 4 weeks when eyes were processed for light microscopy. RESULTS: All eyes from Group A showed significant vascular dilation, conjunctival hyperemia and neovascularization on the iris surface, after LAF injection. No vascular changes were observed in Group B. CONCLUSIONS: The intravitreal injection of microspheres containing the LAF can induce rubeosis iridis in rabbits and could be used as a simple experimental model for iris neovascularization.


Subject(s)
Angiogenesis Inducing Agents/toxicity , Glaucoma, Neovascular/etiology , Iris/blood supply , Latex/toxicity , Neovascularization, Pathologic/chemically induced , Angiogenesis Inducing Agents/administration & dosage , Animals , Disease Models, Animal , Disease Progression , Drug Carriers , Female , Fluorescein Angiography , Fundus Oculi , Glaucoma, Neovascular/pathology , Intravitreal Injections , Iris/drug effects , Lactic Acid , Latex/administration & dosage , Microspheres , Neovascularization, Pathologic/complications , Neovascularization, Pathologic/pathology , Polyglycolic Acid , Polylactic Acid-Polyglycolic Acid Copolymer , Rabbits , Risk Factors
14.
J Thromb Haemost ; 9(1): 24-32, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20961396

ABSTRACT

AIMS: Antiplatelet therapy with aspirin and clopidogrel is recommended for 1 year after drug-eluting stent (DES) implantation or myocardial infarction. However, the discontinuation of antiplatelet therapy has become an important issue as recent studies have suggested a clustering of ischemic events within 90 days of clopidogrel withdrawal. The objective of this investigation was to explore the hypothesis that there is a transient 'rebound' increase in platelet reactivity within 3 months of clopidogrel discontinuation. METHODS AND RESULTS: In this prospective study, platelet function was assessed in patients taking aspirin and clopidogrel for at least 1 year following DES implantation. Platelet aggregation was measured using a modification of light transmission aggregometry in response to multiple concentrations of adenosine diphosphate (ADP), epinephrine, arachidonic acid, thrombin receptor activating peptide and collagen. Clopidogrel was stopped and platelet function was reassessed 1 week, 1 month and 3 months later. Thirty-two patients on dual antiplatelet therapy were recruited. Discontinuation of clopidogrel increased platelet aggregation to all agonists, except arachidonic acid. Platelet aggregation in response to ADP (2.5, 5, 10, and 20 µm) and epinephrine (5 and 20 µm) was significantly increased at 1 month compared with 3 months following clopidogrel withdrawal. Thus, a transient period of increased platelet reactivity to both ADP and epinephrine was observed 1 month after clopidogrel discontinuation. CONCLUSIONS: This study demonstrates a transient increase in platelet reactivity 1 month after clopidogrel withdrawal. This phenomenon may, in part, explain the known clustering of thrombotic events observed after clopidogrel discontinuation. This observation requires confirmation in larger populations.


Subject(s)
Angioplasty, Balloon, Coronary/instrumentation , Drug-Eluting Stents , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation/drug effects , Ticlopidine/analogs & derivatives , Adenosine Diphosphate , Aged , Angioplasty, Balloon, Coronary/adverse effects , Arachidonic Acid , Aspirin/administration & dosage , Clopidogrel , Collagen , Drug Administration Schedule , Drug Therapy, Combination , Epinephrine , Female , Humans , Ireland , Male , Middle Aged , Peptides , Platelet Aggregation Inhibitors/adverse effects , Platelet Function Tests , Predictive Value of Tests , Prospective Studies , Thrombosis/blood , Thrombosis/etiology , Ticlopidine/administration & dosage , Ticlopidine/adverse effects , Time Factors , Treatment Outcome
15.
Clin Neurophysiol ; 121(7): 1092-101, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20202901

ABSTRACT

OBJECTIVE: Two indicators of otolithic function were used to measure dynamic otolith function in the same patients both during an acute attack of Ménière's disease (MD) and in the quiescent period between attacks. METHODS: The early negative component (n10) of the ocular vestibular-evoked myogenic potential (the oVEMP) to brief 500 Hz bone conducted vibration (BCV) stimulation of the forehead, in the midline at the hairline (Fz) was recorded by surface EMG electrodes just beneath both eyes while the patient looked up. It has been proposed that the n10 component of the oVEMP to 500 Hz Fz BCV indicates utricular function. It has been proposed that the early positive component (p13) of the cervical vestibular-evoked myogenic potential (the cVEMP) recorded by surface electrodes on both tensed SCM neck muscles to 500 Hz Fz BCV indicates saccular function. RESULTS: Sixteen healthy control subjects tested on two occasions showed no detectable change in the symmetry of oVEMPs or cVEMPs to 500 Hz Fz BCV. In response to 500 Hz Fz BCV 15 early MD patients tested at both attack and quiescent phases showed a dissociation: there was a significant increase in contralesional of n10 of the oVEMP during the attack compared to quiescence but a significant decrease in the ipsilesional p13 of the cVEMP during the attack compared to quiescence. CONCLUSIONS: During an MD attack, dynamic utricular function in the affected ear as measured by the n10 of the oVEMP to 500 Hz Fz BCV is enhanced, whereas dynamic saccular function in the affected ear as measured by the p13 of the cVEMP to 500 Hz Fz BCV is not similarly affected. SIGNIFICANCE: The MD attack appears to affect different otolithic regions differentially.


Subject(s)
Evoked Potentials, Auditory/physiology , Forehead/physiology , Meniere Disease/diagnosis , Meniere Disease/physiopathology , Physical Stimulation/methods , Vestibule, Labyrinth/physiology , Vibration , Acute Disease , Adult , Aged , Female , Humans , Male , Middle Aged , Orbit/physiology , Physical Stimulation/instrumentation , Young Adult
16.
Pharmazie ; 65(1): 9-14, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20187572

ABSTRACT

UV-VIS-Spectrophotometric and spectrofluorimetric methods have been developed and validated allowing the quantification of chloroaluminum phthalocyanine (CIAIPc) in nanocarriers. In order to validate the methods, the linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, and selectivity were examined according to USP 30 and ICH guidelines. Linearities range were found between 0.50-3.00 microg x mL(-1) (Y = 0.3829 X [CIAIPc, microg x mL(-1)] + 0.0126; r = 0.9992) for spectrophotometry, and 0.05-1.00 microg x mL(-1) (Y = 2.24 x 10(6) X [CIAIPc, microg x mL(-1)] + 9.74 x 10(4); r = 0.9978) for spectrofluorimetry. In addition, ANOVA and Lack-of-fit tests demonstrated that the regression equations were statistically significant (p<0.05), and the resulting linear model is fully adequate for both analytical methods. The LOD values were 0.09 and 0.01 microg x mL(-1), while the LOQ were 0.27 and 0.04 microg x mL(-1) for spectrophotometric and spectrofluorimetric methods, respectively. Repeatability and intermediate precision for proposed methods showed relative standard deviation (RSD) between 0.58% to 4.80%. The percent recovery ranged from 98.9% to 102.7% for spectrophotometric analyses and from 94.2% to 101.2% for spectrofluorimetry. No interferences from common excipients were detected and both methods were considered specific. Therefore, the methods are accurate, precise, specific, and reproducible and hence can be applied for quantification of CIAIPc in nanoemulsions (NE) and nanocapsules (NC).


Subject(s)
Drug Carriers/analysis , Indoles/analysis , Nanoparticles/analysis , Organometallic Compounds/analysis , Radiation-Sensitizing Agents/analysis , Algorithms , Analysis of Variance , Chromatography, High Pressure Liquid , Indicators and Reagents , Reference Standards , Reproducibility of Results , Solubility , Spectrometry, Fluorescence , Spectrophotometry, Ultraviolet
17.
Curr Eye Res ; 35(1): 56-62, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20021255

ABSTRACT

PURPOSE: To create a retinal neovascularization experimental model using intravitreal injection of microspheres loaded with latex-derived angiogenic fraction. METHODS: Thirty-two albino New Zealand rabbits, divided in 4 groups of 8 animals, were enrolled in this study. Rabbits in groups I, II, and III received one intravitreal injection of PLGA (L-lactide-co-glycolide) microspheres with 10, 30, and 50 microg of latex-derived angiogenic fraction into their right eyes, respectively, and group IV received 0.1 ml of microspheres without the angiogenic fraction. Weekly follow-up with ophthalmoscopy and fluorescein angiography was performed; the rabbits were sacrificed in the 4th week and their eyes processed for light microscopy. RESULTS: All eyes from group I demonstrated increased retinal vascular tortuosity, observed from 14 days after injection and maintained for 28 days, otherwise without new vessels detection. All group II eyes showed vascular changes similar to group I. Fifty percent of the eyes from group II rabbits developed retinal neovascularization 21 days after injection. All eyes from group III demonstrated significant vascular tortuosity and retinal new vessels 2 weeks after injection, progressing to fibrovascular proliferation and tractional retinal detachment. No vascular changes or retinal new vessels were observed in group IV eyes. Light microscopy confirmed the existence of new vessels previously seen on fluorescein angiography, in retinal sections adjacent to the optic disc, not observed in sections at the same area in the control group. CONCLUSION: Thirty- and 50-microg microspheres containing latex-derived angiogenic fraction injected into the vitreous cavity induced retinal neovascularization in rabbits.


Subject(s)
Angiogenesis Inducing Agents/toxicity , Disease Models, Animal , Latex/toxicity , Retinal Neovascularization/chemically induced , Retinal Vessels/drug effects , Animals , Drug Carriers , Female , Fluorescein Angiography , Lactic Acid , Microspheres , Ophthalmoscopy , Polyglycolic Acid , Polylactic Acid-Polyglycolic Acid Copolymer , Rabbits , Retinal Neovascularization/diagnosis , Retinal Vessels/pathology
18.
Photodiagnosis Photodyn Ther ; 6(3-4): 207-13, 2009.
Article in English | MEDLINE | ID: mdl-19932453

ABSTRACT

Photodynamic therapy (PDT) is based on the association of a light source and light sensitive agents in order to cause the selective death of tumor cells. To evaluate topical 5-aminolaevulinic acid (5-ALA) and diode laser photodynamic single session therapy single session for non-melanoma skin cancer (NMSC), a long-term follow-up was performed. Nineteen Bowen's disease (BD) and 15 basal cell carcinoma (BCC) lesions were submitted to 6-h topical and occlusive 20% 5-ALA plus DMSO and EDTA, and later were exposed to 630 nm diode laser, 100 or 300 J cm(-2) dose. At 3 months tumor-free rate was 91.2% (31/34) whereas at 60 months, 57.7% (15/26), slightly higher in BCC (63.6%; 7/11). The relation between the reduction of the clinical response and the increase of tumor dimension observed at 18 months was lost at 60 months. The sBCC recurrence was earlier compared to the nBCC one. ALA-PDT offered important advantages: it is minimally invasive, an option for patients under risk of surgical complications; clinical feasibility; treatment of multiple lesions in only one session or lesions in poor healing sites and superior esthetical results. However, the recurrence rate increase after ALA-PDT diode laser single session can be observed at long-term follow-up, and the repetitive sessions, an additional advantage of the method, is strongly recommended. The clinical response and recurrence time seem to be related to the laser light dose and NMSC types/sub-types, thickness and dimension, which must be considered for the choice of the ALA-PDT.


Subject(s)
Aminolevulinic Acid/analogs & derivatives , Bowen's Disease/drug therapy , Carcinoma, Basal Cell/drug therapy , Lasers, Semiconductor/therapeutic use , Photochemotherapy , Skin Neoplasms/drug therapy , Administration, Topical , Adult , Aged , Aminolevulinic Acid/therapeutic use , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Skin Neoplasms/surgery , Time Factors
20.
Autoimmun Rev ; 8(3): 233-7, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18708166

ABSTRACT

Rheumatoid arthritis [RA] is one of the most common and severe autoimmune rheumatic diseases, diagnosed primarily according to clinical manifestations and radiological reports. For many years, laboratory diagnosis of rheumatoid arthritis has relied on the detection of rheumatoid factor [RF], as established by the ACR criteria. A recent test to detect antibodies towards citrullinated peptides, called the anti-CCP assay, showed a similar sensitivity but a more elevated specificity than the RF test. Our intention was the recognition of an optimal diagnostic strategy that exhibits the highest sensitivity and specificity for RA detection. To this purpose, we examine the usefulness of autoantibodies in RA testing, evaluating the diagnostic performance of conventional and innovative assays for RF detection, and ELISA anti-CCP test, for anti-CCP antibodies detection, by a prospective study. Multiplex cytofluorimetric test appeared to be more sensitive and specific than nephelometric assay for RF detection. Hence, a novel combined approach, significantly increasing the diagnostic sensitivity for RA, was planned, employing the multiplex RF test in combination with the anti-CCP test.


Subject(s)
Arthritis, Rheumatoid/diagnosis , Citrulline , Early Diagnosis , Enzyme-Linked Immunosorbent Assay/methods , Peptides , Rheumatoid Factor/blood , Biomarkers/blood , Citrulline/chemistry , Citrulline/immunology , Disease Progression , Humans , Peptides/chemistry , Peptides/immunology , Predictive Value of Tests , Prospective Studies , Rheumatoid Factor/immunology , Sensitivity and Specificity , Severity of Illness Index
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