ABSTRACT
This study aimed to estimate the cost-effectiveness of four therapeutic approaches available for mucosal leishmaniasis in Brazil: miltefosine, meglumine antimoniate, combined with and without pentoxifylline, and liposomal amphotericin B. The perspective adopted was that of the Brazilian Unified National Health System (SUS). The outcome of interest was "cured patient", which was analyzed using a decision tree model. Estimates of direct costs and effectiveness were obtained from the scientific literature. Meglumine antimoniate alone was the base comparator strategy; liposomal amphotericin B showed an incremental cost-effectiveness ratio (ICER) of USD 7,409.13 per cured patient, and the combination of meglumine antimoniate with pentoxifylline presented an ICER of USD 85.13. Miltefosine was absolutely dominated, with higher cost and similar effectiveness when compared to meglumine antimoniate. Sensitivity analyses, varying the cost by ±25%, did not change the results. However, when the cost of miltefosine was estimated at less than USD 171.23, this strategy was dominant over meglumine antimoniate alone. The results confirm that treatment with liposomal amphotericin B remains the option with the highest ICER among the approaches analyzed. Miltefosine may be cost-effective based on the variation in the acquisition price, which deserves attention because it is the only available oral option. The non-accounting of other aspects prevent the use of these results immediately to support decision-making, but they point out the need to negotiate the prices of drugs available for mucosal leishmaniasis and indicates the need of encouraging technology transfer or other actions aimed at expanding the performance of the Brazilian national industrial complex.
Subject(s)
Amphotericin B , Antiprotozoal Agents , Cost-Benefit Analysis , Leishmaniasis, Mucocutaneous , Meglumine Antimoniate , Meglumine , Organometallic Compounds , Pentoxifylline , Phosphorylcholine , Humans , Phosphorylcholine/analogs & derivatives , Phosphorylcholine/economics , Phosphorylcholine/therapeutic use , Leishmaniasis, Mucocutaneous/drug therapy , Leishmaniasis, Mucocutaneous/economics , Antiprotozoal Agents/economics , Antiprotozoal Agents/therapeutic use , Amphotericin B/economics , Amphotericin B/therapeutic use , Brazil , Meglumine/economics , Meglumine/therapeutic use , Meglumine Antimoniate/therapeutic use , Meglumine Antimoniate/economics , Organometallic Compounds/therapeutic use , Organometallic Compounds/economics , Pentoxifylline/economics , Pentoxifylline/therapeutic use , Drug Therapy, Combination/economics , National Health Programs/economicsABSTRACT
PURPOSE: The aim of the present study was to determine the methodological quality of systematic reviews that evaluated the effectiveness of pentoxifylline and tocopherol (PENTO) in the treatment of osteoradionecrosis of the jaw (ORNJ) and medication-related osteonecrosis of the jaw (MRONJ). METHODS: Searches were performed in Databases including PubMed, Scopus, LILACS, DARE, Cochrane Library, and SIGLE through OpenGrey until March 2024, were evaluated by two independent reviewers to answer the following question: Is the use of PENTO protocol effective in the treatment of ORNJ or for the treatment of MRONJ? RESULTS: A total of 256 articles were initially identified; however, following the use of appropriate inclusion and exclusion criteria, five systematic reviews were identified for detailed analysis. The final study sample comprised 588 patients: 397 patients with ORN and 197 patients with MRONJ who were treated with PENTO. The total recovery of individuals who used the PENTO protocol was 62,2 % for ORN and 100 % for MRONJ, with a follow-up period of 1 month to 10 years. The methodological quality of the studies was assessed using the AMSTAR 2 tool, in which four were of low quality and 1 moderate quality. CONCLUSION: The treatment of ORN and MRONJ with pentoxifylline and tocopherol has shown good results in the studies presented, with a partial or total reduction in bone exposure. However, the low quality of the relevant reports highlights the need for primary and secondary studies with better methodological rigor to reduce bias and provide reassurance for this treatment option.
Subject(s)
Osteoradionecrosis , Pentoxifylline , Tocopherols , Humans , Jaw Diseases/therapy , Jaw Diseases/drug therapy , Jaw Diseases/chemically induced , Jaw Diseases/diagnosis , Osteoradionecrosis/drug therapy , Osteoradionecrosis/therapy , Osteoradionecrosis/etiology , Osteoradionecrosis/pathology , Pentoxifylline/therapeutic use , Pentoxifylline/administration & dosage , Tocopherols/therapeutic use , Tocopherols/administration & dosage , Treatment Outcome , Systematic Reviews as TopicABSTRACT
Three-dimensional cell cultures have improved the evaluation of drugs for cancer therapy, due to their high similarity to solid tumors. In melanoma, autophagy appears to show a dual role depending on the progression of the disease. p62 protein has been proposed for the evaluation of autophagic flux since its expression is an indicator of the state of autophagy. Pentoxifylline (PTX) and Norcantharidin (NCTD) are drugs that have been shown to possess anticancer effects. In this work, we used B16F1 mouse melanoma cells in two-dimensional (2D) monolayer cultures and three-dimensional (3D) spheroids to test the effect of PTX and NCTD over the p62 expression. We analyzed the effect on p62 expression through Western blot and immunofluorescence assays. Our results indicate that PTX decreases p62 expression in both cell culture models, while Norcantharidin increases its expression in 3D cultures at 24 h. Therefore, these drugs could have a potential therapeutic use for the regulation of autophagy in melanoma, depending on the state of evolution of the disease.
Subject(s)
Autophagy , Bridged Bicyclo Compounds, Heterocyclic , Pentoxifylline , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Animals , Mice , Pentoxifylline/pharmacology , Autophagy/drug effects , Cell Line, Tumor , Melanoma, Experimental/metabolism , Melanoma, Experimental/drug therapy , Melanoma, Experimental/pathology , Cell Culture Techniques , Sequestosome-1 Protein/metabolism , Sequestosome-1 Protein/genetics , Antineoplastic Agents/pharmacology , Spheroids, Cellular/drug effects , Spheroids, Cellular/metabolismABSTRACT
Cervical cancer (CC) is one of the most common and deadly types of female cancer worldwide. Late diagnosis in CC increases the risk of tumor cells spreading to distant organs (metastasis). The epithelial-mesenchymal transition (EMT) is a fundamental process of cancer metastasis. Inflammation can lead to tumor progression, EMT induction, and metastasis. The inflammatory microenvironment is a potent inducer of EMT; inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-α) and Transforming growth factor-beta (TGF-ß1) activate transcriptional factors such as STAT3, Snail, Smad, and the Nuclear Factor kappa light-chain-enhancer of activated beta cells (NF-κΒ), which drive EMT. Anti-inflammatory compounds may be an option in the disruption of EMT. PenToXifylline (PTX) possesses potent anti-inflammatory effects by inhibiting NF-κB activity. In addition, PTX exerts an anti-fibrotic effect by decreasing Smad2/3/4. We hypothesize that PTX could exert anti-EMT effects. CaSki human cervical tumor cells were exposed to TNF-α 10 ng/mL and TGF-ß1 alone or in combination for 5 days. Our results revealed that TNF-α and TGF-ß1 induced N-cadherin and Vimentin, confirming the induction of EMT. Furthermore, the combination of cytokines synergized the expression of mesenchymal proteins, enhanced IκBα and p65 phosphorylation, and upregulated Serpin family E member 1 (SERPINE1) mRNA. PTX pretreatment prior to the addition of TNF-α and TGF-ß1 significantly reduced N-cadherin and Vimentin levels. To our knowledge, this is the first time that this effect of PTX has been reported. Additionally, PTX reduced the phosphorylation of IκB-α and p65 and significantly decreased SERPINE1 expression, cell proliferation, migration, and invasion. In conclusion, PTX may counteract EMT in cervical cancer cells by decreasing the NF-κB and SERPINE1.
Subject(s)
Pentoxifylline , Uterine Cervical Neoplasms , Female , Humans , NF-kappa B/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Transforming Growth Factor beta1/metabolism , Epithelial-Mesenchymal Transition , Vimentin/metabolism , Pentoxifylline/pharmacology , Uterine Cervical Neoplasms/drug therapy , Cadherins/metabolism , Cell Line, Tumor , Tumor Microenvironment , Plasminogen Activator Inhibitor 1/geneticsABSTRACT
PURPOSE: To assess the prophylaxis effect of pentoxifylline and tocopherol (PENTO) on the frequency and severity of medication-related osteonecrosis of the jaw (MRONJ) diagnosed at three months in patients with cancer submitted to tooth extractions during the treatment with bone-modifying agents. METHODS: This case series was conducted at the outpatient dental clinic of the Instituto de Medicina Integral Prof. Fernando Figueira (IMIP) between April 2021 and April 2022. Patients ⥠18 years old were included; those with maxillary metastasis or who performed head or neck radiotherapy were excluded. The PENTO protocol was prescribed two weeks before and two weeks after the tooth extraction, and patients were reassessed one week, one month, and three months after the extraction. The main outcome was the development of MRONJ. RESULTS: Of the 114 screened patients, 17 were included; they were aged between 43 and 73 years and were mostly female (88.2%). Thirty-two tooth extractions were performed (22 in the maxilla and 10 in the mandible). Breast cancer was the most predominant neoplasm (70.6%), being metastatic in 35.3% of patients. Also, all patients used intravenous bisphosphonates. Stage 1 MRONJ was diagnosed in three patients (17.6%), representing three (9.4%) of all tooth extractions. The repair of MRONJ was achieved 30 days after the PENTO protocol. CONCLUSION: The prophylaxis use of PENTO reduced the severity of injuries, was well-tolerated, and showed patient compliance.
Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw , Bone Density Conservation Agents , Breast Neoplasms , Pentoxifylline , Humans , Female , Adult , Middle Aged , Aged , Adolescent , Male , Pentoxifylline/therapeutic use , Tocopherols/therapeutic use , Bone Density Conservation Agents/adverse effects , Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology , Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control , Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy , Breast Neoplasms/drug therapy , Tooth Extraction/adverse effects , Tooth Extraction/methods , Diphosphonates/adverse effectsABSTRACT
BACKGROUND: Myocardial perfusion defect (MPD) is common in chronic Chagas cardiomyopathy (CCC) and is associated with inflammation and development of left ventricular systolic dysfunction. We tested the hypothesis that pentoxifylline (PTX) could reduce inflammation and prevent the development of MPD in a model of CCC in hamsters. METHODS AND RESULTS: We investigated with echocardiogram and rest myocardial perfusion scintigraphy at baseline (6-months after T. cruzi infection/saline) and post-treatment (after additional 2-months of PTX/saline administration), female Syrian hamsters assigned to 3 groups: T. cruzi-infected animals treated with PTX (CH + PTX) or saline (CH + SLN); and uninfected control animals (CO). At the baseline, all groups showed similar left ventricular ejection fraction (LVEF) and MPD areas. At post-treatment evaluation, there was a significant increase of MPD in CH + SLN group (0.8 ± 1.6 to 9.4 ± 9.7%), but not in CH + PTX (1.9 ± 3.0% to 2.7 ± 2.7%) that exhibited MPD area similar to CO (0.0 ± 0.0% to 0.0 ± 0.0%). The LVEF decreased in both infected groups. Histological analysis showed a reduced inflammatory infiltrate in CH + PTX group (395.7 ± 88.3 cell/mm2), as compared to CH + SLN (515.1 ± 133.0 cell/mm2), but larger than CO (193.0 ± 25.7 cell/mm2). The fibrosis and TNF-α expression was higher in both infected groups. CONCLUSIONS: The prolonged use of PTX is associated with positive effects, including prevention of MPD development and reduction of inflammation in the chronic hamster model of CCC.
Subject(s)
Chagas Cardiomyopathy , Chagas Disease , Pentoxifylline , Cricetinae , Animals , Female , Chagas Cardiomyopathy/diagnostic imaging , Pentoxifylline/pharmacology , Pentoxifylline/therapeutic use , Stroke Volume , Ventricular Function, Left , Tomography, X-Ray Computed , Inflammation , PerfusionABSTRACT
Chronic Chagas cardiomyopathy (CCC) is one of the leading causes of morbidity and mortality due to cardiovascular disorders in endemic areas of Chagas disease (CD), a neglected tropical illness caused by the protozoan parasite Trypanosoma cruzi. CCC is characterized by parasite persistence and inflammatory response in the heart tissue, which occur parallel to microRNA (miRNA) alterations. Here, we investigated the miRNA transcriptome profiling in the cardiac tissue of chronically T. cruzi-infected mice treated with a suboptimal dose of benznidazole (Bz), the immunomodulator pentoxifylline alone (PTX), or the combination of both (Bz+PTX), following the CCC onset. At 150 days post-infection, Bz, PTX, and Bz+PTX treatment regimens improved electrocardiographic alterations, reducing the percentage of mice afflicted by sinus arrhythmia and second-degree atrioventricular block (AVB2) when compared with the vehicle-treated animals. miRNA Transcriptome profiling revealed considerable changes in the differential expression of miRNAs in the Bz and Bz+PTX treatment groups compared with the control (infected, vehicle-treated) group. The latter showed pathways related to organismal abnormalities, cellular development, skeletal muscle development, cardiac enlargement, and fibrosis, likely associated with CCC. Bz-Treated mice exhibited 68 differentially expressed miRNAs related to signaling pathways like cell cycle, cell death and survival, tissue morphology, and connective tissue function. Finally, the Bz+PTX-treated group revealed 58 differentially expressed miRNAs associated with key signaling pathways related to cellular growth and proliferation, tissue development, cardiac fibrosis, damage, and necrosis/cell death. The T. cruzi-induced upregulation of miR-146b-5p, previously shown in acutely infected mice and in vitro T. cruzi-infected cardiomyocytes, was reversed upon Bz and Bz+PTX treatment regimens when further experimentally validated. Our results further our understanding of molecular pathways related to CCC progression and evaluation of treatment response. Moreover, the differentially expressed miRNAs may serve as drug targets, associated molecular therapy, or biomarkers of treatment outcomes.
Subject(s)
Chagas Cardiomyopathy , Chagas Disease , MicroRNAs , Nitroimidazoles , Pentoxifylline , Trypanocidal Agents , Trypanosoma cruzi , Animals , Mice , Chagas Cardiomyopathy/drug therapy , Pentoxifylline/pharmacology , Pentoxifylline/therapeutic use , Transcriptome , Disease Models, Animal , Trypanosoma cruzi/genetics , Chagas Disease/parasitology , Nitroimidazoles/pharmacology , Nitroimidazoles/therapeutic use , MicroRNAs/genetics , Fibrosis , Gene Expression Profiling , Trypanocidal Agents/pharmacologyABSTRACT
PURPOSE: This systematic review aimed to determine whether the pentoxifylline and tocopherol (PENTO) protocol effectively reduce the risk of osteoradionecrosis (ORN) in patients undergoing tooth extraction after head and neck radiotherapy. METHODS: We searched PubMed, SCOPUS, LILACS, EMBASE, Web of Science, and Cochrane databases up to August 2022. We considered only studies that included patients diagnosed with head and neck cancer undergoing tooth extraction with PENTO prophylaxis after radiotherapy. RESULTS: Of the 642 studies identified, 4 were included. Across the included studies, 387 patients had 1871 teeth extracted while on PENTO prophylaxis. The interval of the PENTO protocol differed among the studies included. Overall, a total of 12 (3.1%) patients had ORN, whereas at the individual tooth level analysis the ORN rate was 0.9%. CONCLUSIONS: Insufficient evidence exists to promote using the PENTO protocol before dental extractions to prevent ORN.
Subject(s)
Head and Neck Neoplasms , Osteoradionecrosis , Pentoxifylline , Humans , Tocopherols/therapeutic use , Pentoxifylline/therapeutic use , Osteoradionecrosis/prevention & control , Osteoradionecrosis/drug therapy , Head and Neck Neoplasms/radiotherapy , Tooth Extraction , Retrospective StudiesABSTRACT
This work aimed to assess the effects of the coadministration of pentoxifylline (PTX) on the pharmacokinetic profile of florfenicol (FFC) after intramuscular administration in rabbits. Ten New Zealand white rabbits, 1 year of age and 3.9 ± 0.1 kg body weight, were assigned according to a randomized block design to Group 1 (FFC): treated with 30 mg/kg of FFC intramuscularly, and Group 2 (PTX + FFC) treated with an oral dose of 30 mg/kg PTX 45 min before the intramuscular injection of 30 mg/kg FFC. Blood samples were collected before and at different times between 0.5 and 12.0 h after drug administration. FFC plasma concentrations were determined by high-performance liquid chromatography. Results showed that IM injection of the long-acting formulation of FFC in rabbits resulted in a slow increase in mean plasma concentrations reaching a Cmax of 3.09 ± 0.52 ug/mL at 2.8 ± 0.45 h (Tmax ) after drug administration. While coadministration of PTX and FFC decreased the time to achieve the maximal concentration by modifying the absorption of FFC without changes in the other pharmacokinetic parameters.
Subject(s)
Pentoxifylline , Thiamphenicol , Rabbits , Animals , Anti-Bacterial Agents/pharmacokinetics , Thiamphenicol/pharmacokinetics , Injections, Intramuscular/veterinary , Administration, OralABSTRACT
BACKGROUND: Osteoradionecrosis of the jaws (ORNJ) is a severe and challenging complication of head and neck radiation therapy. Despite its aggressiveness and controversy respect to its efficacy, surgical intervention remains the main treatment modality. Nevertheless, due to advances in the understanding of ORNJ physiopathology, new treatment alternatives such as the combination of pentoxifylline with tocopherol (PENTO) have emerged. The aim of this systematic review was to assess the reported efficacy of PENTO for the treatment of ORNJ. Material and Methods: Studies were search using Pubmed, The Cochrane Library, Scopus, and Web of Science data bases following the PRISMA guidelines. Inclusion criteria were cohort, case series, randomized or non-randomized clinical studies published in English including human subjects who received PENTO as treatment for ORN of the jaws. Results: Eleven articles met the inclusion criteria and were included for data analysis. All studies reported patients with complete mucosal coverage with no exposed bone (considered healthy) after PENTO treatment, ranging from 16.6% to 100% of the patients, depending on the study. Clinical improvement or disease stabilization was reported between 7.6% and 66.6% of studied individuals, while disease progression was seen in only 5 studies involving 7.6 - 32% of patients. CONCLUSIONS: PENTO treatment achieved a complete disease control in a significant number of patients in all studies. However, there is no standardized protocol for administering the therapy. It is necessary to determine the pharmacological doses and to evaluate the benefits of adding antibiotics and clodronate. Good quality clinical trials are needed to develop a successful algorithm for the management of ORN of the jaws.
Subject(s)
Head and Neck Neoplasms , Osteoradionecrosis , Pentoxifylline , Humans , Tocopherols/therapeutic use , Pentoxifylline/therapeutic use , Osteoradionecrosis/drug therapy , Osteoradionecrosis/etiology , Head and Neck Neoplasms/complications , JawABSTRACT
BACKGROUND: Mucosal or mucocutaneous leishmaniasis is the most severe form of tegumentary leishmaniasis due to its destructive character and potential damage to respiratory and digestive tracts. The current treatment recommendations are based on low or very low-quality evidence, and pentavalent antimonial derivatives remain strongly recommended. The aim of this review was to update the evidence and estimate the cure rate and safety profile of the therapeutic options available for mucosal leishmaniasis (ML) in the Americas. METHODOLOGY: A systematic review was conducted in four different databases and by different reviewers, independently, to evaluate the therapeutic efficacy and toxicity associated with different treatments for ML. All original studies reporting cure rates in more than 10 patients from American regions were included, without restriction of design, language, or publication date. The risk of bias was assessed by two reviewers, using different tools according to the study design. The pooled cure rate based on the latest cure assessment reported in the original studies was calculated grouping all study arms addressing the same intervention. The protocol for this review was registered at the International Prospective Register of Systematic Reviews, PROSPERO: CRD42019130708. PRINCIPAL FINDINGS: Twenty-seven original studies from four databases fulfilled the selection criteria. A total of 1,666 patients with ML were treated predominantly with pentavalent antimonials in Brazil. Other interventions, such as pentamidine, miltefosine, imidazoles, aminosidine sulfate, deoxycholate and lipidic formulations of amphotericin B (liposomal, lipid complex, colloidal dispersion), in addition to combinations with pentoxifylline, allopurinol or sulfa were also considered. In general, at least one domain with a high risk of bias was identified in the included studies, suggesting low methodological quality. The pooled cure rate based on the latest cure assessment reported in the original studies was calculated grouping all study arms addressing the same intervention. It was confirmed that antimony is still the most used treatment for ML, with only moderate efficacy (possibly increased by combining with pentoxifylline). There is already evidence for the use of miltefosine for ML, with a cure rate similar to antimony, as observed in the only direct meta-analysis including 57 patients (OR: 1.2; 0.43-3.49, I2 = 0). It was possible to gather all descriptions available about adverse events reported during ML treatment, and the toxicity reflected the pattern informed in the manufacturers' technical information. CONCLUSIONS: This study provides an overview of the clinical experience in the Americas related to ML treatment and points out interventions and possible combinations that are eligible to be explored in future well-designed studies.
Subject(s)
Leishmaniasis, Mucocutaneous , Pentoxifylline , Humans , Antimony , Leishmaniasis, Mucocutaneous/drug therapyABSTRACT
Type 2 diabetes mellitus (T2D) during pregnancy is characterized by high levels of reactive oxygen species and pro-inflammatory factors in the placenta. Once these reactive species reach the foetus, they trigger physiological adaptations that allow the foetus to survive, but programme the organism to develop metabolic disorders in adulthood. The male reproductive system is highly susceptible to foetal programming. This study aimed to investigate the effects of intrauterine exposure to T2D on testicular histomorphometry and redox homeostasis of adult rats and evaluate the effects of maternal treatment with metformin and pentoxifylline. Female rats were induced to T2D, then treated with metformin and pentoxifylline, or co-treated with both drugs. The females were mated, the male offspring were sacrificed on postnatal day 90, and the testicles were collected for analysis. Metformin protected the tubular compartment, with the maintenance of the Sertoli cell population and daily sperm production. Pentoxifylline attenuated the effects of diabetes on Leydig cells, in addition to stimulating testosterone production and lowering lipid peroxidation. Intrauterine exposure to T2D results in important testicular alterations that compromise gonadal function, and the co-treatment with metformin and pentoxifylline may represent a promising therapy that attenuates these effects by combining the positive influences in both the tubular and interstitial compartments of the testicular parenchyma.
Subject(s)
Diabetes Mellitus, Type 2 , Metformin , Pentoxifylline , Animals , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Female , Lipid Peroxidation , Male , Metformin/pharmacology , Oxidative Stress , Pentoxifylline/metabolism , Pentoxifylline/pharmacology , Pregnancy , Rats , Reactive Oxygen Species/metabolism , Semen , Spermatogenesis , Testis , Testosterone/pharmacologyABSTRACT
In the heart tissue of acutely Trypanosoma cruzi-infected mice miR-145-5p and miR-146b-5p are, respectively, downregulated and upregulated. Here, we used the H9C2 rat cardiomyoblast cell line infected with the Colombian T. cruzi strain to investigate the parasite-host cell interplay, focusing on the regulation of miR-145-5p and miR-146b-5p expression. Next, we explored the effects of interventions with the trypanosomicidal drug Benznidazole (Bz) alone or combined with Pentoxifylline (PTX), a methylxanthine derivative shown to modulate immunological and cardiac abnormalities in a model of chronic chagasic cardiomyopathy, on parasite load and expression of miR-145-5p and miR-146b-5p. The infection of H9C2 cells with trypomastigote forms allowed parasite cycle with intracellular forms multiplication and trypomastigote release. After 48 and 144 h of infection, upregulation of miR-145-5p (24 h: 2.38 ± 0.26; 48 h: 3.15 ± 0.9-fold change) and miR-146b-5b (24 h: 2.60 ± 0.46; 48 h: 2.97 ± 0.23-fold change) was detected. The peak of both miRNA levels paralleled with release of trypomastigote forms. Addition of 3 µM and 10 µM of Bz 48 h after infection reduced parasite load but did not interfere with miR-145-5p and miR-146b-5p levels. Addition of PTX did not interfere with Bz-induced parasite control efficacy. Conversely, combined Bz + PTX treatment decreased the levels of both microRNAs, resembling the expression levels detected in non-infected H9C2 cells. Moreover, the use of miR-145-5p and miR-146b-5p mimic/inhibitor systems before infection of H9C2 cells decreased parasite load, 72 h postinfection. When H9C2 cells were treated with miR-145-5p and miR-146b-5p mimic/inhibitor 48 h after infection, all the used systems, except the miR-146b-5p inhibitor, reduced parasite load. Altogether, our data indicate that these microRNAs putatively control signaling pathways crucial for parasite-host cell interaction. Thus, miR-145-5p and miR-146b-5p deserve to be further investigated as biomarkers of parasite control and tools to identify therapeutic adjuvants to etiological treatment in Chagas disease.
Subject(s)
Host-Parasite Interactions/drug effects , MicroRNAs/genetics , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Animals , Cell Line , Dose-Response Relationship, Drug , Drug Combinations , Gene Expression Regulation , Host-Parasite Interactions/genetics , MicroRNAs/antagonists & inhibitors , MicroRNAs/metabolism , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/parasitology , Nitroimidazoles/pharmacology , Oligoribonucleotides/genetics , Oligoribonucleotides/metabolism , Pentoxifylline/pharmacology , Rats , Signal Transduction , Trypanosoma cruzi/genetics , Trypanosoma cruzi/growth & developmentABSTRACT
Introduction: American tegumentary leishmaniasis (ATL), which can present as either cutaneous (CL) or mucosal leishmaniasis (ML), is endemic in South America, and first-line antimonial treatments are known for their wide range of adverse effects (AEs). Growing reports of drug resistance increase the urgency of the need for better treatment options. The objective of this pilot clinical trial was to assess the efficacy of and AEs associated with the oral combination of miltefosine and pentoxifylline based on a post hoc analysis. Methods: A pilot, randomized, open-label clinical trial was performed. The experimental group (M+P) received 50 mg twice a day (BID) miltefosine and 400 mg three times a day (TID) pentoxifylline, and the control group (A+P) received 20 mg Sb+V/kg/day intravenously and 400 mg TID pentoxifylline. Patients with ML received treatment for 28 days, and patients with CL received treatment for 20 days. Results: Forty-three patients were included: 25 with ML and 18 with CL caused by L.(V.) braziliensis. AEs were more frequent in the A+P group (p=0.322), and there was a need for treatment interruption due to severe AEs (p=0.027). Patients with CL had a higher chance of achieving a cure (p=0.042) and a higher risk of AEs (p=0.033). There was no difference in the chance of a cure based on the treatment (p=0.058). Conclusion: In this pilot randomized clinical trial, M+P treatment and A+P treatment yielded similar cure rates, and the former was associated with a lower risk of AEs. Future studies with more patients and longer follow-up are recommended.
Subject(s)
Antiprotozoal Agents , Leishmaniasis, Cutaneous , Pentoxifylline , Antiprotozoal Agents/therapeutic use , Humans , Leishmaniasis, Cutaneous/drug therapy , Pentoxifylline/therapeutic use , Phosphorylcholine/analogs & derivatives , Pilot Projects , Treatment Outcome , United StatesABSTRACT
Leishmaniasis is a worldwide problem and has been neglected in a wide range of fields, from diagnosis to treatment. This report describes a case of mucosal leishmaniasis, which may developped after seven decades of an inadequately treated cutaneous lesion. A female patient, 79 years old, from the non-endemic area for leishmaniasis in northern Paraná, presenting mucosal lesion in the nose and throat, reported an "angry ulcer" treated inappropriately as a child when she lived in an endemic region of the state of São Paulo. Indirect immunofluorescence and direct parasite screening were positive. Polymerase chain reaction detected a parasite belonging to the subgenus Leishmania (Viannia) sp. Due to patients limitations, such as low weight and advanced age, the therapeutic model adopted was the combined small doses of Glucantime™ to pentoxifylline, which ensured treatment success.
Subject(s)
Leishmaniasis, Mucocutaneous/prevention & control , Meglumine Antimoniate/therapeutic use , Pentoxifylline/therapeutic use , Trypanocidal Agents/therapeutic use , Aged , Brazil , Drug Therapy, Combination , Female , Humans , Leishmania/drug effectsABSTRACT
BACKGROUND: Protective effects of Bacillus Calmette-Guérin (BCG) vaccination and clofazimine and dapsone treatment against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. Patients at risk for leprosy represent an interesting model for assessing the effects of these therapies on the occurrence and severity of coronavirus disease 2019 (COVID-19). We assessed the influence of leprosy-related variables in the occurrence and severity of COVID-19. METHODOLOGY/PRINCIPAL FINDINGS: We performed a 14-month prospective real-world cohort study in which the main risk factor was 2 previous vaccinations with BCG and the main outcome was COVID-19 detection by reverse transcription polymerase chain reaction (RT-PCR). A Cox proportional hazards model was used. Among the 406 included patients, 113 were diagnosed with leprosy. During follow-up, 69 (16.99%) patients contracted COVID-19. Survival analysis showed that leprosy was associated with COVID-19 (p<0.001), but multivariate analysis showed that only COVID-19-positive household contacts (hazard ratio (HR) = 8.04; 95% CI = 4.93-13.11) and diabetes mellitus (HR = 2.06; 95% CI = 1.04-4.06) were significant risk factors for COVID-19. CONCLUSIONS/SIGNIFICANCE: Leprosy patients are vulnerable to COVID-19 because they have more frequent contact with SARS-CoV-2-infected patients, possibly due to social and economic limitations. Our model showed that the use of corticosteroids, thalidomide, pentoxifylline, clofazimine, or dapsone or BCG vaccination did not affect the occurrence or severity of COVID-19.
Subject(s)
COVID-19/epidemiology , COVID-19/therapy , Leprosy/drug therapy , Leprosy/epidemiology , Adrenal Cortex Hormones/therapeutic use , BCG Vaccine/administration & dosage , Brazil/epidemiology , COVID-19/diagnosis , COVID-19 Testing , Clofazimine/therapeutic use , Cohort Studies , Dapsone/therapeutic use , Humans , Pentoxifylline/therapeutic use , Prospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Survival Analysis , Thalidomide/therapeutic use , COVID-19 Drug TreatmentABSTRACT
The degradation of Pentoxifylline (PXF) was achieved successfully by green energy in a built-in solar photocatalytic system using hybrid LiCs ferrites (Li0.5Cs0.5FeO2) as magnetically recoverable photocatalysts. Kinetics showed a first-order reaction rate with maximum PXF removal of 94.91% at mildly acidic pH; additionally, the ferromagnetic properties of catalyst allowed recovery and reuse multiple times, reducing costs and time in degradation processes. The degradation products were identified by HPLC-MS and allowed us to propose a thermodynamically feasible mechanism that was validated through DFT calculations. Additionally, toxicity studies have been performed in bacteria and yeast where high loadings of Cs showed to be harmful to Staphylococcus aureus (MIC≥ 4.0 mg/mL); Salmonella typhi (MIC≥ 8.0 mg/mL) and Candida albicans (MIC≥ 10.0 mg/mL). The presented setup shows effectiveness and robustness in a degradation process using alternative energy sources for the elimination of non-biodegradable pollutants.
Subject(s)
Pentoxifylline , Water Pollutants, Chemical , Catalysis , Kinetics , Photolysis , Sunlight , Titanium , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/toxicityABSTRACT
INTRODUCCIÓN: existe una gran variedad de tratamientos orales para la Enfermedad de La Peyronie (EP), pero ninguno demostró ser efectivo. En los últimos años se ha propuesto a la Pentoxifilina (PTX) como un potencial agente para su tratamiento. OBJETIVO: evaluar la evolución clínica de los pacientes que recibieron PTX al menos 3 meses durante la fase aguda de la EP. MATERIALES Y MÉTODOS: estudio de cohorte retrospectivo y observacional. Los datos se obtuvieron de las historias clínicas de pacientes con diagnóstico de EP entre enero y octubre de 2017. Para la evaluación objetiva, se utilizaron autofotografías y técnica de Kelami. RESULTADOS: 93 hombres cumplieron con los criterios de inclusión. El tiempo medio de tratamiento con PTX fue de 7,9 meses, y el de seguimiento, 10,8 meses. El 59,1% de los pacientes no tuvo modificaciones en su curvatura, el 9,7% mejoró, mientras que el 31,2% empeoró. De 49 pacientes que penetraban sin dificultad, 34 (69,4%) no tuvieron cambios, 12 (24,5%) pasaron a tener dificultad y 3 (6,1%) se convirtieron en no penetradores (p 0,0001). De los 41 pacientes que tenían dificultad en la penetración, 13 (31,7%) pudieron penetrar sin dificultad, 7 (17,1%) pasaron a no poder hacerlo, mientras que el resto (21 pacientes) se mantuvo sin cambios (p 0,0001). La correlación entre la curvatura inicial y la curvatura luego del tratamiento medido en todos los pacientes fue significativa (p 0,028). CONCLUSIÓN: la PTX podría tener un efecto positivo en estabilizar la enfermedad, y los hombres con EP en fase aguda podrían beneficiarse con el tratamiento.
INTRODUCTION: There is a wide variety of oral treatments for Peyronie's Disease (PD) but none proved to be effective. In recent years, Pentoxifylline (PTX) has been proposed as a potential agent for the treatment. Objective: To evaluate the clinical evolution of patients who received PTX at least 3 months during the acute phase of PD. MATERIALS AND METHODS: Retrospective and observational cohort study. The data were obtained from the clinical records of patients diagnosed with PE between January 2007 and October 2017. For their objective evaluation, autographs and the Kelami technique were used. RESULTS: 93 men met the inclusion criteria. The mean time of treatment with PTX was 7.9 months and the follow-up time was 10.8 months. 59.1% of patients had no changes in their curvature, 9.7% improved, while 31.2% worsened. Of 49 patients who entered without difficulty in penetrating, 34 (69.4%) had no changes, 12 (24.4%) had difficulty and 3 (6.1%) became non-penetrators (p 0.0001). Of the 41 patients who had difficulty in penetrating, 13 (31.7%) could penetrate without difficulty, 7 (17.1%) were unable to do so, while the rest (21 patients) remained unchanged (p. 0.0001). The correlation between initial curvature and curvature after treatment measured in all patients was significant (p 0.028). CONCLUSION: PTX could have a positive effect in stabilizing the disease and men with acute phase PE could benefit with treatment.
Subject(s)
Humans , Male , Adult , Middle Aged , Penile Induration/drug therapy , Pentoxifylline/therapeutic use , Acute Disease , Retrospective Studies , Cohort Studies , Treatment OutcomeABSTRACT
BACKGROUND: The aim of the present study was to evaluate the efficacy of pentoxifylline and tocopherol for the management of osteoradionecrosis of the jaws. METHODS: Twenty-five patients diagnosed with osteoradionecrosis of the jaws treated with pentoxifylline 400 mg + tocopherol 400 mg three times daily (tid) were evaluated. Clinical records and image tests were reviewed. All patients were previously submitted to head and neck radiation therapy and presented with a clinical and radiographic diagnosis of osteoradionecrosis of the jaws. RESULTS: Following therapy with pentoxifylline and tocopherol, 76% (19/25) of the patients showed complete mucosal healing, in which 47.3% (9/19) did not undergo sequestrectomy. From this particular group, 77.7% (7/9) were in stage I and 33.3% (3/9) used the protocol for up to 3 months. Among those who underwent to sequestrectomy, complete mucosal healing was observed in 52.7% (10/19). Among these, 60% (6/10) were in stage I and 100% of the patients were using the protocol for more than 3 months. In all other patients, partial healing of the mucosa was observed since they presented advanced disease. These represented 24% of the sample (6/25), 66.6% (4/6) were in stage III, and 60% (4/6) used the protocol for over 6 months. CONCLUSION: Pentoxifylline and tocopherol may provide effective management of osteoradionecrosis of the jaws, and the association with sequestrectomy may avoid major surgical procedures.