ABSTRACT
Tobacco usage is linked to multiple cancer types and accounts for a quarter of all cancer-related deaths. Tobacco smoke contains various carcinogenic compounds, including polycyclic aromatic hydrocarbons (PAH), though the mutagenic potential of many tobacco-related chemicals remains largely unexplored. In particular, the highly carcinogenic tobacco-specific nitrosamines NNN and NNK form pre-mutagenic pyridyloxobutyl (POB) DNA adducts. In the study presented here, we identified genome-scale POB-induced mutational signatures in cell lines and rat tumors, while also investigating their role in human cancer. These signatures are characterized by T>N and C>T mutations forming from specific POB adducts damaging dT and dC residues. Analysis of 2,780 cancer genomes uncovered POB signatures in â¼180 tumors; from cancer types distinct from the ones linked to smoking-related signatures SBS4 and SBS92. This suggests that, unlike PAH compounds, the POB pathway may contribute uniquely to the mutational landscapes of certain hematological malignancies and cancers of the kidney, breast, prostate and pancreas.
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Pancreatic cancer is one of the most aggressive forms of cancer, and treatment options are limited. One therapeutic approach is to use nanoparticles to deliver the active agent directly to pancreatic cancer cells. Nanoparticles can be designed to specifically target cancer cells, minimizing damage to healthy tissues. Silver nanoparticles have the unique ability to absorb light, especially in the near-infrared (NIR) region. In this study, silver nanoparticles functionalized with IgG molecules were synthesized and administered to pancreatic cancer cell lines. Subsequently, the cells were photo-excited using a 2 W 808 nm laser and further examined in PANC-1 pancreatic cancer cell lines. Flow cytometry and confocal microscopy combined with immunochemical staining were used to examine the interaction between photo-excited silver nanoparticles and pancreatic cancer cells. The photothermal therapy based on IgG-functionalized silver nanoparticles in pancreatic cancer induces dysfunction in the Golgi apparatus, leading to the activation of the caspase-3 apoptotic pathway and ultimately resulting in cellular apoptosis. These findings suggest that our proposed IgG nanoparticle laser treatment could emerge as a novel approach for the therapy of pancreatic cancer.
Subject(s)
Apoptosis , Immunoglobulin G , Metal Nanoparticles , Pancreatic Neoplasms , Photothermal Therapy , Silver , Pancreatic Neoplasms/therapy , Pancreatic Neoplasms/pathology , Humans , Silver/chemistry , Metal Nanoparticles/chemistry , Cell Line, Tumor , Photothermal Therapy/methods , Apoptosis/drug effects , Caspase 3/metabolism , Phototherapy/methodsABSTRACT
Rosmarinic acid is a well-known natural antioxidant and anti-inflammatory compound, and it is one of the polyphenolic compounds found in comfrey plants. Comfrey root also contains allantoin, which helps with new skin regeneration. This study aimed to investigate the healing and skin regeneration process of skin wounds in Wistar rats using creams based on comfrey extract and to correlate the results with active compounds in the extract. The obtained results showed that comfrey root is rich in bioactive compounds, including allantoin, salvianolic acid, and rosmarinic acid, which are known for their great free radical scavenging activity, and the high antioxidant activity of the extract may be mainly due to these compounds. The obtained extract has an antimicrobial effect on Staphylococcus aureus (1530.76/382.69), Escherichia coli (6123.01/6123.01), and Pseudomonas aeruginosa (6123.01/6123.01). The macroscopic evaluation and the histological analysis of the skin defects 14 days after the intervention showed faster healing and complete healing in the skin excisions treated with oil-in-water cream with 20% extract of comfrey as the active ingredient.
Subject(s)
Boraginaceae , Comfrey , Rats , Animals , Allantoin/pharmacology , Plant Extracts/pharmacology , Rats, Wistar , Wound Healing , Antioxidants/pharmacologyABSTRACT
Monosodium glutamate (MSG) is the sodium salt of glutamic acid (GLA), used as a flavour enhancer. MSG is considered a controversial substance. It is incriminated in disturbing the antioxidant system, but also has beneficial effects, as GLA metabolism plays a crucial role in homeostasis. This study highlights which positive or negative aspects of MSG sub-chronic consumption are better reflected in subjects potentially affected by advanced age. Daily doses of MSG were administered to four groups of two-year-old Wistar rats for 90 days: (I) 185 mg/kg bw, (II) 1500 mg/kg bw, (III) 3000 mg/kg bw and (IV) 6000 mg/kg bw, compared to a MSG non-consumer group. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, direct and total bilirubin, total cholesterol, triglycerides, creatinine and urea levels were analysed; stomach, liver and kidney samples were subjected to histopathological analysis. Although, in most cases, there were no statistical differences, interesting aspects of the dose-effect relationship were observed. After MSG sub-chronic consumption, the positive aspects of GLA seem to be reflected better than the negative ones. The hormesis effect, with low-level reactive oxygen species' protective effects and GLA metabolism, may represent the hypothesis of a potential defence mechanism triggered by MSG sub-chronic consumption in ageing rats.
Subject(s)
Antioxidants , Sodium Glutamate , Rats , Humans , Animals , Child, Preschool , Rats, Wistar , Sodium Glutamate/pharmacology , Antioxidants/pharmacology , Kidney/metabolism , Liver/metabolismABSTRACT
Antioxidants have been commonly used in medicine for thousands of years. Clinically, pentoxifylline and Ginkgo biloba have beneficial renal effects. Our study evaluated the nephroprotective effect of Gingko biloba in combination with Pentoxifiln in an experimental model of vancomycin-induced nephrotoxicity. Male Winstar rats were used in 3 groups: CONTROL, VANCO and VANCO+GBI+PTX and each group included 6 rats. Insufficient studies in the literature on the prevention of acute kidney injury by the combination of Ginkgo biloba and pentoxifylline led to the necessity to perform the study. Acute kidney injury was demonstrated by measuring serum values of classical markers such as urea and creatinine but also by measuring the urinary N-acetyl-ß-d-glucosaminidase index, a topical marker in modern medicine. The significant decrease of the biochemical parameters in group III (VANCO+GBI+PTX) compared to group II (VANCO) and values similar to group I (CONTROL), demonstrates, the nephroprotective effect of the use in combination of the two substances.
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Case summary: A 9-month-old male neutered domestic shorthair cat presented 2 weeks after castration with a 48 h history of acute-onset lateral recumbency and severe hindlimb rigidity. Physical examination findings included hyperthermia, tachypnoea, hindlimb rigidity and a healed orchidectomy site. Neurological examination of the head and forelimbs was normal; however, there was a spastic, non-ambulatory paraparesis of the hindlimbs, which was more severe on the left. Abnormal findings included mildly elevated serum creatine kinase levels and on electromyography there was bilateral pathological spontaneous activity of the biceps femoris muscles. A tentative diagnosis of tetanus was made based on clinical presentation. Treatment was initiated with tetanus antitoxin, diazepam, metronidazole, buprenorphine and physiotherapy of the hindlimbs. There was an improvement over the following 20 days. Twenty-five days later the cat presented with acute, painful, non-weightbearing lameness of the left hindlimb. Physical examination was suggestive of craniodorsal coxofemoral joint luxation, which was confirmed radiographically. This was treated with analgesia and rest. A marked clinical improvement was observed at the 3-month follow-up. Relevance and novel information: To our knowledge, there have been no previously published reports of spontaneous coxofemoral joint luxation as a complication of hindlimb localised tetanus infection in cats. This report suggests that coxofemoral luxation should be considered as a possible complication in young cats with hindlimb localised tetanus.
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Objectives/Hypothesis: It is acknowledged that the treatment of chronic rhinosinusitis (CRS) represents an important challenge for rhinology and for social and economic life. At present, one of the most common treatments for CRS is represented by local corticosteroids followed by endoscopic sinus surgery (ESS). Starting from the example of the mesenchymal stem cell's (MSC) capacity to migrate and to modulate a real response in the nasal mucosa of an allergic rhinitis mouse model, we try to obtain a response in a CRS mouse model, using MSC derived by adipose tissue. The aim of this study is to demonstrate that the MSC can be used in CRS treatment and could change its priorities. Methods: Seventy female mice (6 MSC donor mice) were randomized in two stages of study, 32 Aspergillus fumigatus (Af) exposure mice (20 for histological comparison to 1st control mice and 12 for MSC administration, to CRS/MCS model) and 32 control mice (20 for histological comparison to CRS model and 12 for MSC administration and histological control to MSC model); in the first stage, the Aspergillus fumigatus (Af) CRS mouse model was targeted, in this section were included 64 (n = 32) mice (treated and control group). In order to assess the inflammation level (histological analysis), the animals were euthanized; in the second stage MSCs (1 × 106/animal) were administered intravenously to a total of 24 (n = 24) mice (12 mice from the exposed group and 12 mice from the second control group). Results: After 12 weeks of Af intranasal instillation, the inflammation parameters evaluated indicated a severe diffuse chronic inflammation, associated with diffuse severe hyperplasia and mature diffuse squamous metaplasia. The MSCs' injection via the ophthalmic vein induced important histopathological changes in the CRS experimental group, starting with the presence of MSCs in all samples and continuing with the important degenerative character of inflammation. Conclusions: MSC administration demonstrated a real improvement of CRS evolution on the CRS mouse model.
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INTRODUCTION: Birth hypoxia is a leading cause of perinatal mortality and neurological morbidity, resulting in central nervous system injury. Cerebral hypoxia and ischemia can produce a severe brain damage following a typical pattern, defined by selective vulnerability of the brain regions. The neonates are most prone to hypoxic-ischemic injuries due to the lack of efficient antioxidant defense. Neonatal hypoxia-ischemia (HI) in a 7-day-old rat HI model can produce cell death by apoptotic or necrotic mechanisms. The degree of apoptotic or necrotic mechanisms responsible for cell death in neonatal hypoxia-ischemia are not very clear as yet. The form of neuronal death may also depend on the severity of ischemic injury. Necrosis predominates in more severe cases, whereas apoptosis occurs in areas with milder ischemic injury. A human study demonstrated apoptotic and necrotic forms of cell death after hypoxic injury, whereas in some brains from stillbirths, only apoptotic figures were observed. The expression of activated caspase-3 reflects the role of apoptosis in neonatal hypoxic ischemic brain injury. OBJECTIVES: The aim of this study was to evaluate the possible neuroprotective effect of melatonin and hypothermia in hypoxic-ischemic encephalopathy in newborn rats. Local damages induced by hypoxia and ischemia were assessed by evaluating the changes in terms of histology and apoptosis. METHODS: The experiment was conducted on 20 newborn Wistar rats premedicated for seven days with melatonin in a dose of 20 mg/kg/day. On the 7th postnatal day (P7), the newborn rats were exposed to ischemia (by clamping the right carotid artery) and hypobaric hypoxia (8% O2 for 90 minutes) and some groups to hypothermia. RESULTS: In this experimental model of neonatal encephalopathy, melatonin, in a dose of 20 mg/kg/day has neuroprotective effect by reducing the number of cells expressing apoptosis in Cornu Ammonis (CA) (Ammon's Horn) CA1, CA2, CA3 and dentate gyrus of the hippocampus when combined with hypothermia. CONCLUSION: The results of this study prove that melatonin is protective in ischemic-hypoxic brain injuries, but the protection is conditioned in most of the brain regions (excepting cerebral cortex) by conjugation with post-injury hypothermia treatment.
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Background: Establishing the diagnosis of COVID-19 and Pneumocystisjirovecii pulmonary coinfection is difficult due to clinical and radiological similarities that exist between the two disorders. For the moment, fungal coinfections are underestimated in COVID-19 patients. Case presentation: We report the case of a 52-year-old male patient, who presented to the emergency department for severe dyspnea and died 17 h later. The RT-PCR test performed at his admission was negative for SARS-CoV-2. Retesting of lung fragments collected during autopsy revealed a positive result for SARS-CoV-2. Histopathological examination showed preexisting lesions, due to comorbidities, as well as recent lesions: massive lung thromboses, alveolar exudate rich in foam cells, suprapleural and intra-alveolar Pneumocystisjirovecii cystic forms, and bilateral adrenal hemorrhage. Conclusion: COVID-19 and P.jirovecii coinfection should be considered, particularly in critically ill patients, and we recommend the systematic search for P. jirovecii in respiratory samples.
Subject(s)
COVID-19/pathology , Lung/pathology , Pneumonia, Pneumocystis/pathology , Respiratory Insufficiency/pathology , Thrombosis/pathology , Acute Kidney Injury/complications , Acute-On-Chronic Liver Failure/complications , Adrenal Gland Diseases/complications , Adrenal Gland Diseases/pathology , Autopsy , COVID-19/complications , Coinfection/pathology , Exudates and Transudates , Fatal Outcome , Fibrosis , Foam Cells/pathology , Hemorrhage/complications , Hemorrhage/pathology , Humans , Hypertension/complications , Liver Diseases, Alcoholic/complications , Male , Middle Aged , Myocardial Ischemia/complications , Pneumonia, Pneumocystis/complications , Pulmonary Artery/pathology , Pulmonary Veins/pathology , Respiratory Insufficiency/etiology , SARS-CoV-2 , Thrombosis/etiologyABSTRACT
The silver content of the skin regeneration ointments can influence its regeneration process but in the meantime, it can take the benefit of the antibacterial properties of silver by avoiding the bacterial infection of an open wound. In the current study, the skin healing and regeneration capacity of bioactive glass with spherical gold nanocages (BGAuIND) in the Vaseline ointments were evaluated in vivo comparing the bioactive glass (BG)-Vaseline and bioactive glass with spherical gold (BGAuSP)-Vaseline ointments. Spherical gold nanocages are stabilized with silver and as a consequence the BGAuIND exhibits great antibacterial activity. Histological examination of the cutaneous tissue performed on day 8 indicates a more advanced regeneration process in rats treated with BGAuSP-Vaseline. The histopathological examination also confirms the results obtained after 11 days post-intervention, when the skin is completely regenerated at rats treated with BGAuSP-Vaseline compared with the others groups where the healing was incomplete. This result is also confirmed by the macroscopic images of the evolution of wounds healing. As expected, the silver content influences the wound healing process but after two weeks, for all of the post-interventional trials from the groups of rats, the skin healing was completely.
Subject(s)
Glass/chemistry , Gold/chemistry , Metal Nanoparticles/chemistry , Regeneration/drug effects , Silicates/chemistry , Skin/drug effects , Wound Healing/drug effects , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Cell Line , Female , Humans , Rats , Silver/chemistryABSTRACT
Lafora Disease (LD) is a rare, fatal, late-onset, progressive form of myoclonic epilepsy, occurring in humans and dogs. Clinical manifestations of LD usually include seizures, spontaneous and reflex myoclonus with contractions of the neck and limb muscles. We studied the electroencephalogram (EEG) patterns of two beagles in whom LD was subsequently confirmed by genetic testing. In both cases, the EEG recordings, accompanied by electromyography (EMG), have shown similar uncommon patterns. The hypovoltaged background rhythm was interrupted by waxing "crescendo" polyspikes-slow wave complexes appearing 80-250 ms after the start of intermittent photic stimulation, followed by myoclonic jerks after 80-150 ms. This study highlights the value of EEG in establishing a presumptive diagnosis of LD in dogs.
ABSTRACT
BACKGROUND: Carbofuran is a widely used broad-spectrum pesticide that, despite strict regulation and being banned for more than a decade, is still encountered in cases of intentional poisoning in dogs and wildlife. The objective of the study was to provide a complete and detailed description of the pathological, histological and toxicological findings of 7 cases of intentional carbofuran poisoning in dogs. RESULTS: In this retrospective study, 7 cases of carbofuran intoxication recorded from July 2015 to June 2017 were analyzed. Following complete history recording, all cases were examined by complete necropsy and histopathology. Carbofuran intoxication was confirmed in all cases by gas chromatography. The postmortem examination revealed extensive hemorrhaging and congestion located mainly within the respiratory, nervous and cardiovascular systems, accompanied by degeneration and necrosis within the lungs, heart, and kidneys. CONCLUSIONS: Although carbamates have been banned in the European Union, carbamate poisoning is still frequently encountered, especially in wild animals. This paper will contribute to a better understanding of the occurrence and pathogenesis of acute carbofuran exposure in dogs and contribute some peculiar pathological features of this type of poisoning to the current literature.
Subject(s)
Carbofuran/poisoning , Dog Diseases/chemically induced , Insecticides/poisoning , Animals , Autopsy/veterinary , Dog Diseases/mortality , Dog Diseases/pathology , Dogs , Retrospective StudiesABSTRACT
In this study, the antibacterial activity of cerium oxide nanoparticles on two Gram-negative and three Gram-positive foodborne pathogens was investigated. CeO2 nanoparticles (CeO2 nps) were synthesized by a Wet Chemical Synthesis route, using the precipitation method and the Simultaneous Addition of reactants (WCS-SimAdd). The as-obtained precursor powders were investigated by thermal analysis (TG-DTA), to study their decomposition process and to understand the CeO2 nps formation. The composition, structure, and morphology of the thermally treated sample were investigated by FTIR, Raman spectroscopy, X-ray diffraction, TEM, and DLS. The cubic structure and average particle size ranging between 5 and 15 nm were evidenced. Optical absorption measurements (UV-Vis) reveal that the band gap of CeO2 is 2.61 eV, which is smaller than the band gap of bulk ceria. The antioxidant effect of CeO2 nps was determined, and the antibacterial test was carried out both in liquid and on solid growth media against five pathogenic microorganisms, namely Escherichia coli, Salmonella typhimurium, Listeria monocytogenes, Staphylococcus aureus, and Bacillus cereus. Cerium oxide nanoparticles showed growth inhibition toward all five pathogens tested with notable results. This paper highlights the perspectives for the synthesis of CeO2 nps with controlled structural and morphological characteristics and enhanced antibacterial properties, using a versatile and low-cost chemical solution method.
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BACKGROUND: Left ventricular noncompaction (LVNC) is a rare form of cardiomyopathy currently described in humans and cats. It consists of a spongy myocardium characterized by prominent trabeculation and deep recesses involving more than 50% of the ventricular thickness. We describe the clinical and pathological features of LVNC combined with tricuspid valve dysplasia, double-orifice tricuspid valve and severe pulmonary stenosis in a puppy. In addition, we briefly review the LVNC causes, pathogenesis, forms and current diagnostic criteria. CASE PRESENTATION: A seven-week-old intact German Shorthaired Pointer-cross male was presented with a poor body condition, exercise intolerance and dyspnea. Clinical exam identified a bilateral systolic murmur (grade IV/VI over the right heart base and grade III/VI over the left heart base). Echocardiography identified tricuspid valve dysplasia, mild mitral regurgitation, and severe pulmonic stenosis with a trans-valvar systolic pressure gradient of 106 mmHg. Left ventricular noncompaction was diagnosed by necropsy and further confirmed histopathologically by the presence of two distinct myocardial layers: an inner noncompacted zone covering more than 50% of ventricular thickness containing prominent trabeculation and deep recesses, and an outer zone of compact myocardium. CONCLUSIONS: This is the first case describing LVNC in a canine patient, supporting the introduction of this form of heart disease as a differential diagnosis for cardiomyopathies in juvenile and adult dogs.
Subject(s)
Cardiomyopathies/veterinary , Dog Diseases/congenital , Heart Defects, Congenital/veterinary , Heart Ventricles/pathology , Animals , Cardiomyopathies/diagnostic imaging , Cardiomyopathies/pathology , Dog Diseases/diagnostic imaging , Dogs , Echocardiography/veterinary , Heart Defects, Congenital/pathology , Male , Pulmonary Valve Stenosis/veterinary , Tricuspid Valve/abnormalitiesABSTRACT
In the present study, scaffolds based on alginate-pullulan-bioactive glass-ceramic with 0.5 and 1.5 mol % copper oxide were orthotopically implanted in experimental rat models to assess their ability to heal an induced bone defect. By implying magnetic resonance and imaging scans together with histological evaluation of the processed samples, a progressive healing of bone was observed within 5 weeks. Furthermore, as the regenerative process continued, new bone tissue was formed, enhancing the growth of irregular bone spicules around the scaffolds. A significantly higher amount of new bone was formed (37%) in the defect that received the composite with 1.5 mol % CuO (in glass-ceramic matrix) content implant. Nevertheless, the bone regeneration obtained by scaffold with 0.5 mol % CuO implanted is comparable with the alginate-pullulan-ß-tricalcium phosphate/hydroxiapatite composite implant. The assessed amount of new bone formed was found to be between 29.75 and 37.15% for all the composition involved in the present study. During this process a regeneration process was shown when the alginate-pullulan composite materials were involved, fact that indicate the great potential of these materials to be used in tissue engineering.
Subject(s)
Alginates/chemistry , Bone Regeneration , Ceramics/chemistry , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Animals , Biocompatible Materials/chemistry , Bone Substitutes , Bone and Bones , Durapatite , Electrochemistry , In Vitro Techniques , Luminescence , Magnetic Resonance Imaging , Male , Microscopy, Electron, Scanning , Osteocalcin/chemistry , Pain Management , Polymers/chemistry , Rats , Rats, WistarABSTRACT
. BACKGROUND: Wound healing of the nasal mucosa after endoscopic sinus surgery (ESS) is frequently complicated by scaring and consequently recurrences are encountered. Methods of optimizing results have been sought. In the present study we evaluated the effects of a powerful antioxidant, astaxanthin, on nasal mucosa healing after surgery, comparing it to the extensively studied properties of dexamethasone. MATERIALS AND METHODS: 63 Wistar rats were used. The nasal mucosa from one side was damaged employing the brushing method. They were randomly divided into three experimental groups, one treated with astaxanthin, the second treated with dexamethasone and the third one acted as the control and was given normal saline. The rats were killed on days 5, 14 and 28 following injury. We observed the temporal evolution of the wound healing process and quantified the results by assessing four parameters: the epithelial thickness index (ETI), the subepithelial thickness index (STI), the goblet cell count and the subepithelial fibrosis index (SFI). RESULTS: At 28 days, the ETI was significantly lower in the astaxanthin group (p < 0.05) compared to the other two groups. The STI was also lower in the astaxanthin group (p < 0.05), but comparable to the dexamethasone group at 28 days. The goblet cell count was higher in the astaxanthin group. The SFI had similar results in both dexamethasone and astaxanthin groups, with lower values compared to the control group. In the astaxanthin group there was no synechia formation. CONCLUSION: Astaxanthin given in the post injury period significantly decreases fibrosis, inhibits synechia development and significantly decreases subepithelial fibrosis. Moreover, it has no general or local toxic effects.
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Psoriasis vulgaris, a chronic inflammatory skin disorder, is the result of immune mediated processes, genetic background and environmental factors. Prolactin and the vascular endothelial growth factor seem to play a key role in psoriasis pathogenesis regarding hyperproliferation of epidermal keratinocytes and dermal vascular ectasia. The aim of the study was to investigate the expression of tumor necrosis factor-α (TNF-α), vascular endothelial growth factor receptor 2 (VEGFR2) and prolactin receptor (PRLR) in psoriatic skin by immunohistochemical analysis and to evaluate the correlation with disease severity. Two skin biopsies, psoriatic lesion and perilesional skin, obtained by punch biopsy from 19 nontreated psoriasis patients were examined in hematoxylin and eosin staining and immunohistochemistry (IHC) for TNF-α, VEGFR2 and PRLR. The indirect IHC reaction was carried out automatically and visualized by 3,3-diaminobenzidine (DAB) technique. The average number of DAB-positive cells and the intensity of cell staining were quantified on a predefined scale. The results show a significant difference in the quantity and distribution of TNF-α positive cells in the two sample groups. In psoriatic plaque skin, an increased expression of TNF-α was found in the perivascular dermis and epidermic keratinocytes. In perilesional skin the immunostaining was predominant in the basal layer keratinocytes, while in psoriatic plaque, all the layers were positively marked, with stronger expression at the base. A statistically significant difference was found between the intensity of the immunostaining in the two types of tissue. Positive cells for VEGFR2 and PRL were identified in the basal layer keratinocyte cells (VEGFR2), sweat glands and hair outer shaft sheath (PRLR), without significant differences between the two types of samples. Our findings confirm the importance of TNF-α in psoriasis pathogenesis and a positive correlation with lesions severity. No significant differences were found for VEGFR2 and PRLR, but additional studies are necessary to establish their role.
ABSTRACT
As an integrated approach to defeat diabetic retinopathy, a common complication of diabetes leading to vision loss, a delivery vehicle able to transport resveratrol (Rv) directly into retina pigmented epithelial D407 cells was designed. Rv, a molecule with known therapeutic potential, was successfully inserted into a microcapsule based on porous CaCO3 templates revealing an encapsulation efficiency of 96.8⯱â¯4.0%. Four alternative layers of polyelectrolytes were deposited via electrostatic-driven layer-by-layer assembly approach on the template and covered by rhodamine 6G (Rh6G). The as-designed PMs-Rv-Rh6G microcapsules were internalized into D407 cells grown in normal and high glucose-induced inflammation conditions, being able to cross the cellular membrane and localize near the nucleus after 24â¯h treatment. The metabolic activity of D407 cells was not diminished by PMs-Rv-Rh6G even after 24â¯h treatment, meaning that the microcapsules do not exert any toxicity toward the cells, based on WST-1 and lactate dehydrogenase assays. Notably, the PMs-Rv-Rh6G treatment is able to inhibit the vascular endothelial growth factor (VEGF) protein, as was proved by the ELISA assay. Therefore, the proposed PMs-Rv-Rh6G microcapsules could be implemented as a potential self-reporting intraocular Rv-delivery vehicle with anti-VEGF activity in the management of diabetic retinopathy.
Subject(s)
Angiogenesis Inhibitors/pharmacology , Drug Delivery Systems , Glucose/metabolism , Resveratrol/pharmacology , Retinal Pigment Epithelium/metabolism , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Angiogenesis Inhibitors/chemistry , Cell Line , Drug Carriers/chemistry , Glucose/pharmacology , Humans , Inflammation/chemically induced , Inflammation/metabolism , Particle Size , Porosity , Resveratrol/chemistry , Retinal Pigment Epithelium/drug effects , Rhodamines/chemistry , Surface Properties , Vascular Endothelial Growth Factor A/metabolismABSTRACT
BACKGROUND: A century of debates on the taxonomy of members of the Metastrongyloidea Molin, 1861 led to many reclassifications. Considering the inconstant genus assignation and lack of genetic data, the main aim of this study was to support the validity of the genus Perostrongylus Schlegel, 1934, previously considered a synonym of Aelurostrongylus Cameron, 1927, based on new molecular phylogenetic data and to understand its evolutionary relationships with other metastrongyloid nematodes. RESULTS: Specimens of lungworm collected from European badgers in Germany, Romania and Bosnia and Herzegovina were morphologically and molecularly (rDNA, cox1) characterized. From a phylogenetic standpoint, Perostrongylus is grouped with high support together with the genera Filaroides van Beneden, 1858 and Parafilaroides Dougherty, 1946 and includes probably two species: Perostrongylus falciformis (Schlegel, 1933), a parasite of Meles meles in Europe and P. pridhami (Anderson, 1962), a parasite of Neovison vison in North America. Perostrongylus and Aelurostrongylus are assigned to different clades. Aelurostrongylus becomes a monotypic genus, with the only species Aelurostrongylus abstrusus (Railliet, 1898). In addition, we provide morphological and morphometric data for the first-stage (L1), second-stage (L2), and third-stage (L3) larvae of P. falciformis and describe their development in experimentally infected Cornu aspersum snails. The pathological and histopathological lesions in lungs of infected European badgers are also described. This is the first record of P. falciformis in Romania. CONCLUSIONS: Molecular phylogenetic and morphological data support the validity of the genus Perostrongylus, most probably with two species, P. falciformis in European badgers and P. pridhami in minks in North America. The two genera clearly belong to two different clades: Perostrongylus is grouped together with the genera Filaroides and Parafilaroides (both in the family Filaroididae Schulz, 1951), whereas Aelurostrongylus belongs to a clade with no sister groups.
Subject(s)
Life Cycle Stages , Metastrongyloidea/classification , Mustelidae/parasitology , Snails/parasitology , Strongylida Infections/veterinary , Animals , Bosnia and Herzegovina , Female , Germany , Larva , Lung/parasitology , Lung/pathology , Male , Metastrongyloidea/genetics , Metastrongyloidea/growth & development , Metastrongyloidea/isolation & purification , North America , Phylogeny , Romania , Strongylida Infections/parasitology , Strongylida Infections/pathology , Strongylida Infections/transmissionABSTRACT
BACKGROUND: There is a need for experimental animal models for inflammatory bowel diseases (IBD), but no proposed model has been unanimously accepted. OBJECTIVES: The aim of this study was to develop 2 affordable models of IBD in rats and to compare them. MATERIAL AND METHODS: We produced IBD in rats using either dextran sodium sulfate (DSS) or 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). The requirements for experimental models were: a predictable clinical course, histopathology and inflammation similar to human ulcerative colitis (UC) and Crohn's disease (CD). The effect of acute administration of DSS and TNBS on oxidative stress (as measured by the assessment of glutathione peroxidase - GPx) was verified. The activity of whole blood GPx was measured using a commercially available Randox kit (Crumlin, UK). RESULTS: The administration of DSS increased GPx activity compared to the control and TNBS-treated groups, but not to a statistically significant degree. Histological examination of the colonic mucosa following the administration of DSS showed multifocal erosions with minimal to mild inflammatory infiltrate, mainly by polymorphonuclear cells (PMN), lymphocytes and plasma cells. For TNBS-induced colitis, the histological changes manifested as multifocal areas of ulcerative colitis with mild to severe inflammatory infiltrate. Whole blood GPx values displayed a direct dependence on the chemical agent used. Our results show a correlation between histopathology, proinflammatory state and oxidative stress. CONCLUSIONS: The experimental DSSor TNBS-induced bowel inflammation used in this study corresponds to human IBD and is reproducible with characteristics indicative of acute inflammation in the case of the protocols mentioned.