ABSTRACT
Toxoplasmosis poses a global health threat, ranging from asymptomatic cases to severe, potentially fatal manifestations, especially in immunocompromised individuals and congenital transmission. Prior research suggests that oregano essential oil (OEO) exhibits diverse biological effects, including antiparasitic activity against Toxoplasma gondii. Given concerns about current treatments, exploring new compounds is important. This study was to assess the toxicity of OEO on BeWo cells and T. gondii tachyzoites, as well as to evaluate its effectiveness in in vitro infection models and determine its direct action on free tachyzoites. OEO toxicity on BeWo cells and T. gondii tachyzoites was assessed by MTT and trypan blue methods, determining cytotoxic concentration (CC50), inhibitory concentration (IC50), and selectivity index (SI). Infection and proliferation indices were analyzed. Direct assessments of the parasite included reactive oxygen species (ROS) levels, mitochondrial membrane potential, necrosis, and apoptosis, as well as electron microscopy. Oregano oil exhibited low cytotoxicity on BeWo cells (CC50: 114.8 µg/mL ± 0.01) and reduced parasite viability (IC50 12.5 ± 0.06 µg/mL), demonstrating 9.18 times greater selectivity for parasites than BeWo cells. OEO treatment significantly decreased intracellular proliferation in infected cells by 84% after 24 h with 50 µg/mL. Mechanistic investigations revealed increased ROS levels, mitochondrial depolarization, and lipid droplet formation, linked to autophagy induction and plasma membrane permeabilization. These alterations, observed through electron microscopy, suggested a necrotic process confirmed by propidium iodide labeling. OEO treatment demonstrated anti-T. gondii action through cellular and metabolic change while maintaining low toxicity to trophoblastic cells.
Subject(s)
Autophagy , Oils, Volatile , Origanum , Reactive Oxygen Species , Toxoplasma , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Toxoplasma/drug effects , Toxoplasma/growth & development , Origanum/chemistry , Humans , Autophagy/drug effects , Reactive Oxygen Species/metabolism , Cell Line , Antiprotozoal Agents/pharmacology , Inhibitory Concentration 50 , Necrosis/drug therapy , Cell Survival/drug effects , Apoptosis/drug effects , Membrane Potential, Mitochondrial/drug effectsABSTRACT
Drug-induced liver injury (DILI) is an adverse reaction to medications and other xenobiotics that leads to liver dysfunction. Based on differential clinical patterns of injury, DILI is classified into hepatocellular, cholestatic, and mixed types; although hepatocellular DILI is associated with inflammation, necrosis, and apoptosis, cholestatic DILI is associated with bile plugs and bile duct paucity. Ursodeoxycholic acid (UDCA) has been empirically used as a supportive drug mainly in cholestatic DILI, but both curative and prophylactic beneficial effects have been observed for hepatocellular DILI as well, according to preliminary clinical studies. This could reflect the fact that UDCA has a plethora of beneficial effects potentially useful to treat the wide range of injuries with different etiologies and pathomechanisms occurring in both types of DILI, including anticholestatic, antioxidant, anti-inflammatory, antiapoptotic, antinecrotic, mitoprotective, endoplasmic reticulum stress alleviating, and immunomodulatory properties. In this review, a revision of the literature has been performed to evaluate the efficacy of UDCA across the whole DILI spectrum, and these findings were associated with the multiple mechanisms of UDCA hepatoprotection. This should help better rationalize and systematize the use of this versatile and safe hepatoprotector in each type of DILI scenarios.
Subject(s)
Chemical and Drug Induced Liver Injury , Cholestasis , Liver Diseases , Humans , Ursodeoxycholic Acid/therapeutic use , Ursodeoxycholic Acid/pharmacology , Cholestasis/drug therapy , Liver Diseases/drug therapy , Chemical and Drug Induced Liver Injury/etiology , Necrosis/drug therapy , LiverABSTRACT
OBJECTIVE.: To determine the in vitro antioxidant capacity of Corryocactus brevistylus and its effect on glycemia and the pancreas of alloxan-induced diabetic rats. MATERIALS AND METHODS.: The antioxidant capacity of the hydroethanolic extract of sanky (HEES) was evaluated by assessing its ability to reduce 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric ion (FRAP). We used thirty adult rats, which were induced to diabetes with two doses of alloxan (80mg/kg). Rats were distributed into 5 groups (n=6), all groups received treatment by orogastric route for eight days. Group I received water, group II received metformin 14mg/kg and groups III, IV and V received sanky juice at 1.0; 4.0 and 16 mL/kg, respectively. Glycemia was evaluated by the rapid method (glucometer) (first and eighth day). After treatment, the animals were sacrificed and the pancreas was removed for histopathological study. RESULTS.: The antioxidant capacity of HEES by DPPH showed an IC50 of 0.77 mg/mL; the FRAP method showed a TEAC-FRAP of 22.31µg/mg. Glycemia decreased on the eighth day of treatment, with respect to the first day; a decrease in glycemia was also found in groups III-V, when compared to group I. Histologically, groups I-II presented severe atrophy and moderate necrosis of the islets of Langerhans; groups IV-V presented hypertrophy and mild multifocal necrosis at the islet level. CONCLUSIONS.: The extract of sanky showed antioxidant capacity in vitro and the juice exerts a hypoglycemic and protective effect on the pancreas.
OBJETIVO.: Determinar la capacidad antioxidante in vitro del Corryocactus brevistylus y su efecto sobre la glicemia y páncreas de ratas diabéticas inducidas con aloxano. MATERIALES Y MÉTODOS.: Se evaluó la capacidad antioxidante del extracto hidroetanólico de sanky (EHES) mediante la capacidad de reducir el 2,2-difenil-1-picrilhidracilo (DPPH) y la capacidad de reducir el ion férrico (FRAP). Se utilizaron 30 ratas adultas inducidas a diabetes con dos dosis de aloxano (80mg/kg), formándose cinco grupos (n=6), recibiendo los tratamientos vía orogástrica durante ocho días, el grupo I (agua), II (metformina 14mg/kg), grupos III-IV-V zumo de sanky a 1,0; 4,0 y 16 mL/kg, respectivamente. La glicemia fue evaluada por el método rápido (glucómetro) (primer y octavo día). Terminado el tratamiento los animales fueron sacrificados y se les extrajo el páncreas, para su estudio histopatológico. RESULTADOS.: La capacidad antioxidante del EHES mediante el DPPH, mostró un IC50 de 0,77 mg/mL, y por el método FRAP se observó el TEAC-FRAP de 22,31µg/mg. La glicemia disminuyó en el octavo día de tratamiento, respecto al primer día; también se observó disminución de la glicemia en los grupos III-V, respecto al grupo I. A nivel histológico los grupos I-II presentaron atrofia severa y necrosis moderada de los islotes de Langerhans; los grupos IV-V presentaron hipertrofia y necrosis leve multifocal a nivel del islote. CONCLUSIONES.: El extracto de sanky presenta capacidad antioxidante in vitro y el zumo ejerce un efecto hipoglicemiante y protector en páncreas.
Subject(s)
Antioxidants , Diabetes Mellitus, Experimental , Rats , Animals , Antioxidants/pharmacology , Alloxan/pharmacology , Alloxan/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Blood Glucose , Pancreas/pathology , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Necrosis/drug therapy , Necrosis/pathologyABSTRACT
Moving towards high-grade glioma drug discovery, this study aimed to detect the mechanism of cellular death (apoptosis, necrosis and/or autophagy) induced by three carboranyl-based lead compounds. For that, we performed in U87 MG cells, flow cytometry experiments, as the gold standard technique, as well as confocal microscopy and 1 H-NMR experiments as non-invasive assays. We selected three hybrid leads (1-3) from the in-house-library and the corresponding parent compounds, and recognized tyrosine kinase inhibitors (lapatinib, sunitinib and erlotinib) to put to the test in these experiments. Flow cytometry with Annexin V-FITC/DAPI staining showed that leads 1 and 3 and lapatinib mainly induced necrosis in U87 MG upon a 24 h treatment at IC50 dose; meanwhile, hybrid 2, sunitinib and erlotinib seem to induce apoptosis in such cells. In general, confocal microscopy studies were in agreement with flow cytometry observing loss of cell membrane integrity in necrotic cells and features of apoptosis, that is, chromatin condensation, in apoptotic cells. Finally, NMR results showed that glioblastoma cells treated with hybrid 1, 3 or lapatinib displayed changes in CH2 /CH3 signal ratio and choline signals that could indicate necrotic cell death mechanism: meanwhile, 2-, sunitinib- or erlotinib-treated cells showed apoptotic characteristic behaviors. Additionally, carboranyl-hybrid 2 also produced autophagy in U87 MG cells.
Subject(s)
Antineoplastic Agents , Glioblastoma , Humans , Glioblastoma/drug therapy , Glioblastoma/metabolism , Lapatinib/pharmacology , Lapatinib/therapeutic use , Sunitinib , Erlotinib Hydrochloride/pharmacology , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Apoptosis , Necrosis/drug therapy , Cell ProliferationABSTRACT
In this study, five neolignans were isolated from Saururus cernuus-threo-dihydroguaiaretic acid (1), threo-austrobailignan-6 (2), threo-austrobailignan-5 (3), verrucosin (4), and saucernetin (5)-and have their cytotoxic effects evaluated in prostate cancer cell lines (PC3 and DU145). Initially, using an in silico approach, tested compounds were predicted to be absorbed by the gastrointestinal tract, be able to permeate the blood-brain barrier and did not show any alert in PAINS (pan-assay structures interference). In vitro assays showed that compounds 2, 4, and 5 reduced cell viability of DU145 cell line at 100 µmol/L after 48 h while compounds 1 and 3 showed to be inactive at the same conditions. Furthermore, compounds 4 and 5 reduced cell number as early as in 24 h at 50 µmol/L and compound 2 showed effects at 100 µmol/L in 24 h against both cancer cell lines PC3 and DU145. Studies using flow cytometry were conducted and indicated that compound 4 induced strong necrosis and apoptosis whereas compound 5 induced strong necrosis. Otherwise, less active compound 2 did not show evidence of induction of apoptosis or necrosis, suggesting that its mechanism of action involves inhibition of cell proliferation. In conclusion, compounds 4 and 5 have been shown to be promising cytotoxic agents against prostate cancer cell lines and can be used as a starting point for the development of new drugs for the treatment of prostate cancer.
Subject(s)
Antineoplastic Agents , Lignans , Prostatic Neoplasms , Saururaceae , Male , Humans , Saururaceae/chemistry , Lignans/pharmacology , Lignans/therapeutic use , Antineoplastic Agents/pharmacology , Prostatic Neoplasms/drug therapy , Apoptosis , Cell Line, Tumor , Necrosis/drug therapyABSTRACT
Nicolau syndrome is a rare complication of the parenteral application of various drugs. It is characterized by the appearance of pain, followed by edema, erythema, and then a necrotic plaque. We present the case of a 31-year-old male with this syndrome, after the application of intramuscular benzathine penicillin. The diagnosis was supported by the biopsy. He received treatment with enoxaparin and cilostazol with subsequent improvement.
El síndrome de Nicolau es una complicación infrecuente de la aplicación parenteral de diversos fármacos. Se caracteriza por la aparición de dolor, seguido de edema, eritema y luego una placa necrótica. Se reporta el caso de un hombre de 31 años que presenta este síndrome luego de la aplicación de penicilina benzatínica intramuscular. La biopsia apoyó el diagnóstico. Recibió tratamiento con enoxaparina y cilostazol con posterior mejoría.
Subject(s)
Nicolau Syndrome , Male , Humans , Adult , Nicolau Syndrome/diagnosis , Nicolau Syndrome/drug therapy , Nicolau Syndrome/etiology , Injections, Intramuscular/adverse effects , Penicillin G Benzathine/therapeutic use , Necrosis/complications , Necrosis/drug therapyABSTRACT
PURPOSE: To investigate the effect of different root canal filling materials on the change of failure of the endodontic treatment of necrotic primary teeth. METHODS: A literature search was carried out in PubMed/MEDLINE, CENTRAL, Scopus databases, and grey literature up to July 2022 selecting randomised clinical trials related to research question. Two reviewers independently selected the studies, extracted the data, and assessed the bias risk. Root canal filling materials were grouped according to the main component [iodoform (IOD), calcium hydroxide (CAOH), zinc oxide (ZO) or mix (IOD plus CAOH plus ZO) pastes]. Pairwise and network meta-analyses using the mixed treatment comparisons method were performed to compare the number of events (failure) among treatments. Odds ratio and 95% confidence intervals (CI) for calculated. Post-probabilities among treatments were also calculated and interpreted. RESULTS: From 1186 potentially relevant studies, 17 were selected for full-text analysis, and 7 were included in the meta-analysis, totalizing 263 teeth. In the direct evidence, ZO pastes resulted in a higher chance of failure than IOD pastes (OR 7.07 95% CI 1.02, 62.59). In the indirect evidence, there was no difference between the materials. The IOD pastes presented a high probability (81%) of being the treatment associated to lowest number of failures among all treatments. The CAOH pastes presented the highest probability of being the worst option. Studies showed high bias risk. CONCLUSION: There is currently no scientific evidence of the superiority of any one root canal filling material for endodontic treatment of necrotic primary teeth.
Subject(s)
Root Canal Filling Materials , Humans , Root Canal Filling Materials/therapeutic use , Network Meta-Analysis , Calcium Hydroxide/therapeutic use , Necrosis/drug therapy , Tooth, DeciduousABSTRACT
Lectins isolated from Canavalia ensiformis (ConA) and Canavalia brasiliensis (ConBr) are promising molecules to prevent cell death. Acute pancreatitis, characterized by acinar cell necrosis and inflammation, presents significant morbidity and mortality. This study has investigated the effects of ConA and ConBr in experimental acute pancreatitis and pancreatic acinar cell death induced by bile acid. Pancreatitis was induced by retrograde pancreatic ductal injection of 3% sodium taurocholate (Na-TC) in male Swiss mice. ConA or ConBr (0.1, 1 or 10 mg/kg) were intravenously applied to mice 1 h and 12 h after induction. After 24 h, the severity of pancreatitis was evaluated by serum amylase and lipase, histopathological changes and myeloperoxidase assay. Pancreatic acinar cells were incubated with ConA (200 µg/ml) or ConBr (200 µg/ml) and taurolithocholic acid 3-sulfate (TLCS; 500 µM). Necrosis and changes in mitochondrial membrane potential (ΔÑ°m) were detected by fluorescence confocal microscopy. Treatment (post-insult) with ConA and ConBr decreased pancreatic damage caused by retrograde injection of Na-TC in mice, reducing pancreatic neutrophil infiltration, edema and necrosis. In addition, ConA and ConBr decreased pancreatic acinar cell necrosis and depolarization of ΔÑ°m caused by TLCS. The inhibition of necrosis was prevented by the lectin domain blockade. In conclusion, ConA and ConBr markedly inhibited in vitro and in vivo damage, effects partly dependent on the interaction with mannose residues on acinar cells. These data support the potential application of these proteins for treatment of acute pancreatitis.
Subject(s)
Canavalia , Pancreatitis , Acute Disease , Animals , Anti-Inflammatory Agents , Canavalia/chemistry , Lectins/pharmacology , Male , Mice , Necrosis/drug therapy , Pancreatitis/chemically induced , Pancreatitis/drug therapy , Plant Lectins/chemistry , Seeds/chemistryABSTRACT
Wound infection is frequently reported following snakebite (SB). This study is retrospective. It was conducted in the emergency department and the Intensive Care Unit (ICU) of Cayenne General Hospital between 1 January 2016 and 31 July 2021. We included 172 consecutive patients hospitalized for SB envenoming. All patients were monitored for wound infection. Sixty-three patients received antibiotics at admission (36.6%). The main antibiotic used was amoxicillin-clavulanate (92.1%). Wound infection was recorded in 55 cases (32%). It was 19% in grade 1, 35% in grade 2, and 53% in grade 3. It included abscess (69.1%), necrotizing fasciitis (16.4%), and cellulitis (21.8%). The time from SB to wound infection was 6 days (IQR: 3-8). The main isolated microorganisms were A. hydrophila and M. morganii (37.5% and 18.8% of isolated organisms). Surgery was required in 48 patients (28.1%), and a necrosectomy was performed on 16 of them (33.3%). The independent factors associated with snakebite-associated infection were necrosis (p < 0.001, OR 13.15, 95% CI: 4.04-42.84), thrombocytopenia (p = 0.002, OR: 3.37, 95% CI: 1.59-7.16), and rhabdomyolysis (p = 0.046, OR: 2.29, 95% CI: 1.02-5.19). In conclusion, wound infection following SB is frequent, mainly in grade 2 and 3 envenomed patients, especially those with necrosis, thrombocytopenia, and rhabdomyolysis. The main involved bacteria are A. hydrophila and M. morganii.
Subject(s)
Bacterial Infections/etiology , Snake Bites/complications , Wound Infection/etiology , Adult , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/surgery , Blister/complications , Blister/drug therapy , Blister/surgery , Female , French Guiana , Humans , Male , Middle Aged , Necrosis/complications , Necrosis/drug therapy , Necrosis/surgery , Retrospective Studies , Rhabdomyolysis/complications , Rhabdomyolysis/drug therapy , Rhabdomyolysis/surgery , Snake Bites/drug therapy , Snake Bites/surgery , Thrombocytopenia/complications , Thrombocytopenia/drug therapy , Thrombocytopenia/surgery , Wound Infection/drug therapy , Wound Infection/surgeryABSTRACT
Las miopatías inflamatorias (MI) son un grupo heterogéneo de enfermedades musculares de rara ocurrencia, caracterizadas por inflamación de los distintos componentes del tejido muscular, ya sea de forma aislada o, más comúnmente, en el contexto de una afección sistémica. Las miopatías necrotizantes inmunomediadas (MNIM) constituyen un subtipo de miopatía inflamatoria caracterizada por debilidad muscular proximal, necrosis de miofibrillas con mínimo infiltrado celular inflamatorio en la biopsia muscular e infrecuente compromiso extramuscular asociado1. Si bien existen similitudes clínicas e histopatológicas, el espectro de las miopatías inflamatorias es considerablemente variable. Por este motivo, es fundamental realizar estudios complementarios para la identificación correcta del subtipo de MI a fin de determinar su pronóstico e implementar un adecuado tratamiento. Se presenta el caso de una paciente de 29 años, sin antecedentes personales y heredofamiliares de enfermedad autoinmune ni antecedentes patológicos relevantes, que consulta a la Guardia Médica de nuestra Institución por un cuadro de dolor e impotencia funcional en los cuatro miembros, con debilidad muscular a predominio de cintura escapular y en menor medida pelviana, acompañado de astenia, tendencia al sueño e hiporreactividad.
Inflammatory myopathies (IM) or myositis are a heterogeneous group of muscle diseases of rare occurrence. Such diseases are characterized by inflammation of the different components of muscle tissue, which can occur either in isolation or, more commonly, as part of a systemic disorder. Immune-mediated necrotizing myopathies (IMNM) are a type of autoimmune myopathy characterized by proximal muscle weakness, myofiber necrosis with minimal inflammatory cell infiltrate on muscle biopsy and infrequent extramuscular involvement1. Even though there are clinical and histopathological similarities. The spectrum of inflammatory myopathies is considerably variable. Therefore, the performance of complementary studies is essential for the proper identification of the IM subtype to contribute accurately on treatment so determine the better prognosis. The present article shows the case of a young 29 years old, with no personal and family history background of autoimmune disease and no relevant pathological background. The patient consulted the medical ward of the Institution with pain, functional impairment of upper and lower extremities, muscle weakness mainly located in the pectoral girdle area and, although to a lesser degree, in the pelvic girdle area. It was also associated with asthenia, tendency to drowsiness and hyporeactivity.
Subject(s)
Humans , Female , Adult , Autoimmune Diseases/diagnosis , Myositis/diagnosis , Autoimmune Diseases/classification , Autoimmune Diseases/drug therapy , Myositis/classification , Myositis/drug therapy , Necrosis/diagnosis , Necrosis/drug therapyABSTRACT
BACKGROUND: The search for novel metallic chemical compounds with toxicogenic effects has been of great importance for more efficient cancer treatment. OBJECTIVE: The study evaluated the cytotoxic, genotoxic and mutagenic activity of organoteluran RF07 in the S-180 cell line. METHODS: The bioassays used were cell viability with 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test, evaluation of apoptosis and necrosis using fluorescence and flow cytometry, cytokinesisblock micronucleus test and comet assay. The compound was tested at 1; 2.5 and 5µM. RESULTS: The results showed the cytotoxicity of RF07 at concentrations of 2.5, 5, 10 and 20µM when compared to the negative control. For genotoxicity tests, RF07 showed effects in all concentrations assessed by increased index and frequencies of damage and mutagenic alterations. The compound was also cytotoxic due to the significant decrease in the nuclear division index, with significant values of apoptosis and necrosis. The results of fluorescence and flow cytometry showed apoptosis as the main type of cell death caused by RF07 at 5µM, which is thought to avoid an aggressive immune response of the organism. CONCLUSION: In addition to cytotoxic and genotoxic effects, RF07 creates good perspectives for future antitumor formulations.
Subject(s)
Antineoplastic Agents/chemistry , DNA Damage/drug effects , Organometallic Compounds/chemistry , Sarcoma 180/drug therapy , Spiro Compounds/chemistry , Animals , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Humans , Mice , Mutagenicity Tests , Mutagens/metabolism , Necrosis/drug therapy , Organometallic Compounds/pharmacology , Signal Transduction , Spiro Compounds/pharmacologyABSTRACT
Colorectal cancer is an important concern in modern society. Risk factors such as the diet indicate the need to find healthy food products displaying additional health benefits. This study aimed to characterise and evaluate the impact of the colonic metabolites from the fermented non-digestible fraction of Moringa oleifera (MO) leaves (FNFM) on cell death mechanisms from HT-29 cells. MO leaves were digested in vitro, and the 12 h-colonic extract was obtained. FNFM mainly contained morin and chlorogenic acids (41.97 and 25.33 µg/g sample). Butyric acid was ranked as the most important metabolite of FNFM. The FNFM exerted antiproliferative effect against HT-29 colorectal cancer cells (half lethal concentration, LC50: 5.9 mL/100 mL). Compared to untreated control, LC50 increased H2O2 production (149.43%); induced apoptosis (119.02%), autophagy (75.60%), and necrosis (87.72%). These results suggested that digested MO colonic metabolites exert antiproliferative effect against HT-29 cells, providing additional health benefits associated with MO consumption.
Subject(s)
Apoptosis/drug effects , Autophagy/drug effects , Colon/metabolism , Moringa oleifera/chemistry , Necrosis/drug therapy , Plant Extracts/pharmacology , Plant Leaves/chemistry , Animals , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Fatty Acids, Volatile/metabolism , Fermentation , HT29 Cells , Humans , Hydrogen Peroxide/metabolism , Male , Rats , Rats, WistarABSTRACT
Vascular compromise is a rare but serious complication of dermal filler injection. Vessel occlusion tends to have a more immediate onset of symptoms. We report a case of skin necrosis that started with pain, erythema and edema two days after hyaluronic acid filler on the forehead of a 57-year-old woman. The patient was treated with less than 24 hours the onset of symptoms, leaving discreet scar. The current theories that explain skin necrosis caused by HA fillers include angiospasm and embolization. The frontal region has many anastomoses, the embolized proximal vessel initially did not lead to symptoms. However, the HA inside the artery may have traveled over time and reached a terminal distal branch, which generated localized skin damage and pain. The urgent treatment of arterial occlusion and thromboembolism caused by HA injection is intralesional high-dose hyaluronidase.
Subject(s)
Cicatrix/etiology , Cosmetic Techniques/adverse effects , Dermal Fillers/adverse effects , Hyaluronic Acid/adverse effects , Skin/pathology , Cicatrix/prevention & control , Dermal Fillers/administration & dosage , Female , Forehead , Humans , Hyaluronic Acid/administration & dosage , Hyaluronoglucosaminidase/administration & dosage , Injections, Intralesional , Injections, Subcutaneous/adverse effects , Middle Aged , Necrosis/chemically induced , Necrosis/complications , Necrosis/drug therapy , Skin/drug effects , Treatment OutcomeSubject(s)
Facial Dermatoses/chemically induced , Metronidazole/adverse effects , Rosacea/chemically induced , Skin/pathology , Administration, Cutaneous , Adult , Drug Therapy, Combination , Facial Dermatoses/drug therapy , Female , Humans , Isotretinoin/therapeutic use , Metronidazole/administration & dosage , Necrosis/chemically induced , Necrosis/drug therapy , Prednisolone/therapeutic use , Rosacea/drug therapy , Skin/drug effects , Treatment OutcomeABSTRACT
Human accidents with spiders of the genus Loxosceles are an important health problem affecting thousands of people worldwide. Patients evolve to severe local injuries and, in many cases, to systemic disturbances as acute renal failure, in which cases antivenoms are considered to be the most effective treatment. However, for antivenom production, the extraction of the venom used in the immunization process is laborious and the yield is very low. Thus, many groups have been exploring the use of recombinant Loxosceles toxins, particularly phospholipases D (PLDs), to produce the antivenom. Nonetheless, some important venom activities are not neutralized by anti-PLD antibodies. Astacin-like metalloproteases (ALMPs) are the second most expressed toxin acting on the extracellular matrix, indicating the importance of its inclusion in the antigen's formulation to provide a better antivenom. Here we show the construction of a hybrid recombinant immunogen, called LgRec1ALP1, composed of hydrophilic regions of the PLD and the ALMP toxins from Loxosceles gaucho. Although the LgRec1ALP1 was expressed as inclusion bodies, it resulted in good yields and it was effective to produce neutralizing antibodies in mice. The antiserum neutralized fibrinogenolytic, platelet aggregation and dermonecrotic activities elicited by L. gaucho, L. laeta, and L. intermedia venoms, indicating that the hybrid recombinant antigen may be a valuable source for the production of protective antibodies against Loxosceles ssp. venoms. In addition, the hybrid recombinant toxin approach may enrich and expand the alternative antigens for antisera production for other venoms.
Subject(s)
Antibodies, Neutralizing/pharmacology , Antivenins/pharmacology , Phosphoric Diester Hydrolases/toxicity , Spider Venoms/toxicity , Animals , Antivenins/metabolism , Edema/chemically induced , Edema/drug therapy , Humans , Male , Metalloproteases/metabolism , Mice, Inbred BALB C , Necrosis/chemically induced , Necrosis/drug therapy , Phosphoric Diester Hydrolases/metabolism , Platelet Aggregation/drug effects , Rabbits , Recombinant Proteins/metabolism , Recombinant Proteins/pharmacology , Spider Venoms/metabolism , SpidersABSTRACT
Plant natural products can attenuate the myonecrosis caused by Bothrops snake venom and their phospholipases A2 (PLA2). In this study, we evaluated the effects of two fractions (F4 and F6) from Swietenia macrophylla and purified catechin on the muscle damage caused by a myotoxic PLA2 from Colombian Bothrops asper venom (BaColPLA2) in mice and by Bothrops marmoratus venom from Brazil in mouse phrenic nerve-diaphragm muscle (PND) preparations in vitro. Male mice were injected with PLA2 (50 µg) in the absence or presence of F4, F6, and catechin, in the gastrocnemius muscle and then killed 3, 7, 14, and 28 h later for histopathological analysis of myonecrosis, leukocyte infiltration, and the presence of collagen. Fractions F4 and F6 (500 µg) and catechin (90 µg) significantly reduced the extent of necrosis at all-time intervals. These two fractions and catechin also attenuated the leukocyte infiltration on day 3, as did catechin on day 14. There was medium-to-moderate collagen deposition in all groups up to day 7, but greater deposition on days 14 and 28 in the presence of F6 and catechin. Bothrops marmoratus venom (100 µg/mL) caused slight (~25%) muscle facilitation after 10 minutes and weak neuromuscular blockade (~64% decrease in contractile activity after a 120-minute incubation). Pre-incubation of venom with F4 or F6 abolished the facilitation, whereas catechin, which was itself facilitatory, did not. All three fractions attenuated the venom-induced decrease in muscle contractions. These findings indicate that fractions and catechin from S. macrophylla can reduce the muscle damage caused by Bothrops venom and PLA2. These fractions or their components could be useful for treating venom-induced local damage.
Subject(s)
Catechin/therapeutic use , Crotalid Venoms/toxicity , Meliaceae , Muscle, Skeletal/drug effects , Phospholipases A2/toxicity , Phrenic Nerve/drug effects , Plant Extracts/therapeutic use , Animals , Bothrops , Fibrosis/chemically induced , Fibrosis/drug therapy , Male , Mice, Inbred BALB C , Muscle Contraction/drug effects , Muscle, Skeletal/pathology , Muscle, Skeletal/physiology , Necrosis/chemically induced , Necrosis/drug therapy , Phrenic Nerve/physiologyABSTRACT
PURPOSE: To evaluate the effect of the cilostazol on the evolution of partially avulsed flaps, using experimental model of cutaneous degloving in rat limbs. METHODS: A controlled and randomized experimental study was carried out in which the blood flow and the percentage of flap necrosis were evaluated. We compared the study group, which received cilostazol, and the control group, which received enteral saline solution in the postoperative period. The blood flow in the flap was evaluated through Laser Doppler flowmetry, and a planimetry using the IMAGE J® software was employed for the calculation of the area of necrosis. RESULTS: Enteral administration of cilostazol was associated with a higher mean blood flow in all regions of the flap, with a statistically significant difference in the proximal and middle regions (p<0.001) and a lower percentage of necrotic area in the flap (p<0.001). CONCLUSION: Postoperative enteral administration of cilostazol increased blood flow and decreased the total area of necrosis of avulsed cutaneous flaps of rat limbs.
Subject(s)
Degloving Injuries/drug therapy , Disease Models, Animal , Phosphodiesterase 3 Inhibitors/therapeutic use , Tetrazoles/therapeutic use , Animals , Cilostazol , Degloving Injuries/pathology , Degloving Injuries/surgery , Humans , Laser-Doppler Flowmetry , Lower Extremity/blood supply , Lower Extremity/injuries , Lower Extremity/pathology , Male , Necrosis/drug therapy , Phosphodiesterase 3 Inhibitors/pharmacology , Random Allocation , Rats, Wistar , Reference Values , Regional Blood Flow/drug effects , Reproducibility of Results , Surgical Flaps , Tetrazoles/pharmacology , Time Factors , Treatment OutcomeABSTRACT
Abstract Purpose: To evaluate the effect of the cilostazol on the evolution of partially avulsed flaps, using experimental model of cutaneous degloving in rat limbs. Methods: A controlled and randomized experimental study was carried out in which the blood flow and the percentage of flap necrosis were evaluated. We compared the study group, which received cilostazol, and the control group, which received enteral saline solution in the postoperative period. The blood flow in the flap was evaluated through Laser Doppler flowmetry, and a planimetry using the IMAGE J® software was employed for the calculation of the area of necrosis. Results: Enteral administration of cilostazol was associated with a higher mean blood flow in all regions of the flap, with a statistically significant difference in the proximal and middle regions (p<0.001) and a lower percentage of necrotic area in the flap (p<0.001). Conclusion: Postoperative enteral administration of cilostazol increased blood flow and decreased the total area of necrosis of avulsed cutaneous flaps of rat limbs.
Subject(s)
Humans , Animals , Male , Tetrazoles/therapeutic use , Disease Models, Animal , Phosphodiesterase 3 Inhibitors/therapeutic use , Degloving Injuries/drug therapy , Reference Values , Regional Blood Flow/drug effects , Surgical Flaps , Tetrazoles/pharmacology , Time Factors , Random Allocation , Reproducibility of Results , Treatment Outcome , Rats, Wistar , Laser-Doppler Flowmetry , Lower Extremity/blood supply , Lower Extremity/injuries , Lower Extremity/pathology , Phosphodiesterase 3 Inhibitors/pharmacology , Degloving Injuries/surgery , Degloving Injuries/pathology , Necrosis/drug therapyABSTRACT
Os acidentes causados por aranhas do gênero Loxosceles têm importância na clínica de pequenos animais, mesmo não havendo dados epidemiológicos desses ataques em animais de estimação, dada a gravidade da lesão e possíveis complicações sistêmicas resultantes, tornando indispensável maior conhecimento sobre a espécie e as consequências do envenenamento. O presente trabalho relata a presença de uma lesão dermonecrótica em um felino atribuída a aranha-marrom (Loxosceles sp). O atendimento ocorreu na clínica Empório de Bicho em Caxias do Sul, no estado do Rio Grande do Sul. O animal apresentava uma lesão necrótica em região perineal, com fibrina e secreção purulenta. O tratamento consistiu no uso clorexidina para limpeza, hidrogel, açúcar, Fitofix® e Dersani® como promotores de cicatrização. Após um mês de tratamento, o animal apresentava uma melhora satisfatória.(AU)
Accidents caused by spiders of the genus Loxosceles are important in the small animal clinic, even though there are no epidemiological data on these attacks in pets, given the severity of the lesion and possible systemic complications, it becomes necessary to know more about the species and the consequences of the poisoning. The present work reports the presence of a dermonecrotic lesion in a cat attributed to brown spider (Loxosceles sp). The patient had a necrotic lesion in the perineal region with fibrin and purulent secretion. The treatment consisted of using chlorhexidine for cleaning, hydrogel, sugar, Fitofix® and Dersani® as healing promoters. After one month of treatment, the animal showed a satisfactory improvement.(AU)
Subject(s)
Animals , Cats , Brown Recluse Spider , Necrosis/drug therapy , Necrosis/veterinary , Spider Venoms/poisoning , Animals, Poisonous , Perineum/pathologyABSTRACT
Os acidentes causados por aranhas do gênero Loxosceles têm importância na clínica de pequenos animais, mesmo não havendo dados epidemiológicos desses ataques em animais de estimação, dada a gravidade da lesão e possíveis complicações sistêmicas resultantes, tornando indispensável maior conhecimento sobre a espécie e as consequências do envenenamento. O presente trabalho relata a presença de uma lesão dermonecrótica em um felino atribuída a aranha-marrom (Loxosceles sp). O atendimento ocorreu na clínica Empório de Bicho em Caxias do Sul, no estado do Rio Grande do Sul. O animal apresentava uma lesão necrótica em região perineal, com fibrina e secreção purulenta. O tratamento consistiu no uso clorexidina para limpeza, hidrogel, açúcar, Fitofix® e Dersani® como promotores de cicatrização. Após um mês de tratamento, o animal apresentava uma melhora satisfatória.
Accidents caused by spiders of the genus Loxosceles are important in the small animal clinic, even though there are no epidemiological data on these attacks in pets, given the severity of the lesion and possible systemic complications, it becomes necessary to know more about the species and the consequences of the poisoning. The present work reports the presence of a dermonecrotic lesion in a cat attributed to brown spider (Loxosceles sp). The patient had a necrotic lesion in the perineal region with fibrin and purulent secretion. The treatment consisted of using chlorhexidine for cleaning, hydrogel, sugar, Fitofix® and Dersani® as healing promoters. After one month of treatment, the animal showed a satisfactory improvement.