RESUMO
Lisofylline (LSF) is an anti-inflammatory molecule with high aqueous solubility and rapid metabolic interconversion to its parent drug, pentoxifylline (PTX) resulting in very poor pharmacokinetic (PK) parameters, necessitating high dose and dosing frequency. In the present study, we resolved the physicochemical and pharmacokinetic limitations associated with LSF and designed its oral dosage form as a tablet for effective treatment in type 1 diabetes (T1D). Self-assembling polymeric micelles of LSF (lisofylline-linoleic acid polymeric micelles (LSF-LA PLM)) were optimized for scale-up (6 g batch size) and lyophilized followed by compression into tablets. Powder blend and tablets were evaluated as per USP. LSF-LA PLM tablet so formed was evaluated for in vitro release in simulated biological fluids (with enzymes) and for cell viability in MIN-6 cells. LSF-LA PLM in tablet formulation was further evaluated for intestinal permeability (in situ) along with LSF and LSF-LA self-assembled micelles (SM) as controls in a rat model using single-pass intestinal perfusion (SPIP) study. SPIP studies revealed 1.8-fold higher oral absorption of LSF-LA from LSF-LA PLM as compared to LSF-LA SM and ~5.9-fold higher than LSF (alone) solution. Pharmacokinetic studies of LSF-LA PLM tablet showed greater Cmax than LSF, LSF-LA, and LSF-LA PLM. Designed facile LSF-LA PLM tablet dosage form has potential for an immediate decrease in the postprandial glucose levels in patients of T1D.
Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Jejuno/metabolismo , Ácido Linoleico/farmacocinética , Nanopartículas/metabolismo , Pentoxifilina/análogos & derivados , Perfusão/métodos , Administração Oral , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Formas de Dosagem , Jejuno/efeitos dos fármacos , Ácido Linoleico/administração & dosagem , Ácido Linoleico/síntese química , Masculino , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/química , Pentoxifilina/administração & dosagem , Pentoxifilina/síntese química , Pentoxifilina/farmacocinética , Ratos , Ratos Wistar , ComprimidosRESUMO
Therapeutic options are urgently needed for non-alcoholic fatty liver disease (NAFLD), but development is time-consuming and costly. In contrast, drug repurposing offers the advantages of re-applying compounds that are already approved, thereby reducing cost. Acetylsalicylic acid (ASA) and pentoxifylline (PTX) have shown promise for treatment of NAFLD, but have not yet been tested in combination. Guinea pigs were fed a high-fat diet for 16 weeks and then continued on the diet while being treated with ASA, PTX or ASA+PTX for 8 weeks. Chow-fed animals served as healthy controls. Guinea pigs were CT scanned before intervention start and at intervention end. Animals without steatosis (ie NAFLD) at week 16 were excluded from the data analysis. ASA and PTX alone or in combination did not improve hepatic steatosis, ballooning, inflammation or fibrosis nor did the treatments affect liver enzymes (aminotransferases and alkaline phosphatase) or circulating lipids. Liver triglyceride levels, relative liver weight and hepatic mRNA expression of monocyte chemoattractant protein 1, interleukin 8 and platelet-derived growth factor b were nominally decreased. Thus, in the current study, treatment with ASA and PTX alone or in combination for 8 weeks did not ameliorate NASH or hepatic fibrosis in guinea pigs.
Assuntos
Aspirina/administração & dosagem , Reposicionamento de Medicamentos , Cirrose Hepática/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Pentoxifilina/administração & dosagem , Animais , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada/métodos , Feminino , Cobaias , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Testes de Função Hepática , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologiaRESUMO
BACKGROUND: On the American continent, cutaneous and mucocutaneous leishmaniasis (CL and MCL) are diseases associated with infection by several species of Leishmania parasites. Pentavalent antimonials remain the first-choice treatment. There are alternative interventions, but reviewing their effectiveness and safety is important as availability is limited. This is an update of a Cochrane Review first published in 2009. OBJECTIVES: To assess the effects of interventions for all immuno-competent people who have American cutaneous and mucocutaneous leishmaniasis (ACML). SEARCH METHODS: We updated our database searches of the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, LILACS and CINAHL to August 2019. We searched five trials registers. SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing either single or combination treatments for ACML in immuno-competent people, diagnosed by clinical presentation and Leishmania infection confirmed by smear, culture, histology, or polymerase chain reaction on a biopsy specimen. The comparators were either no treatment, placebo only, or another active compound. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our key outcomes were the percentage of participants 'cured' at least three months after the end of treatment, adverse effects, and recurrence. We used GRADE to assess evidence certainty for each outcome. MAIN RESULTS: We included 75 studies (37 were new), totalling 6533 randomised participants with ATL. The studies were mainly conducted in Central and South America at regional hospitals, local healthcare clinics, and research centres. More male participants were included (mean age: roughly 28.9 years (SD: 7.0)). The most common confirmed species were L. braziliensis, L. panamensis, and L. mexicana. The most assessed interventions and comparators were non-antimonial systemics (particularly oral miltefosine) and antimonials (particularly meglumine antimoniate (MA), which was also a common intervention), respectively. Three studies included moderate-to-severe cases of mucosal leishmaniasis but none included cases with diffuse cutaneous or disseminated CL, considered the severe cutaneous form. Lesions were mainly ulcerative and located in the extremities and limbs. The follow-up (FU) period ranged from 28 days to 7 years. All studies had high or unclear risk of bias in at least one domain (especially performance bias). None of the studies reported the degree of functional or aesthetic impairment, scarring, or quality of life. Compared to placebo, at one-year FU, intramuscular (IM) MA given for 20 days to treat L. braziliensis and L. panamensis infections in ACML may increase the likelihood of complete cure (risk ratio (RR) 4.23, 95% confidence interval (CI) 0.84 to 21.38; 2 RCTs, 157 participants; moderate-certainty evidence), but may also make little to no difference, since the 95% CI includes the possibility of both increased and reduced healing (cure rates), and IMMA probably increases severe adverse effects such as myalgias and arthralgias (RR 1.51, 95% CI 1.17 to 1.96; 1 RCT, 134 participants; moderate-certainty evidence). IMMA may make little to no difference to the recurrence risk, but the 95% CI includes the possibility of both increased and reduced risk (RR 1.79, 95% CI 0.17 to 19.26; 1 RCT, 127 participants; low-certainty evidence). Compared to placebo, at six-month FU, oral miltefosine given for 28 days to treat L. mexicana, L. panamensis and L. braziliensis infections in American cutaneous leishmaniasis (ACL) probably improves the likelihood of complete cure (RR 2.25, 95% CI 1.42 to 3.38), and probably increases nausea rates (RR 3.96, 95% CI 1.49 to 10.48) and vomiting (RR 6.92, 95% CI 2.68 to 17.86) (moderate-certainty evidence). Oral miltefosine may make little to no difference to the recurrence risk (RR 2.97, 95% CI 0.37 to 23.89; low-certainty evidence), but the 95% CI includes the possibility of both increased and reduced risk (all based on 1 RCT, 133 participants). Compared to IMMA, at 6 to 12 months FU, oral miltefosine given for 28 days to treat L. braziliensis, L. panamensis, L. guyanensis and L. amazonensis infections in ACML may make little to no difference to the likelihood of complete cure (RR 1.05, 95% CI 0.90 to 1.23; 7 RCTs, 676 participants; low-certainty evidence). Based on moderate-certainty evidence (3 RCTs, 464 participants), miltefosine probably increases nausea rates (RR 2.45, 95% CI 1.72 to 3.49) and vomiting (RR 4.76, 95% CI 1.82 to 12.46) compared to IMMA. Recurrence risk was not reported. For the rest of the key comparisons, recurrence risk was not reported, and risk of adverse events could not be estimated. Compared to IMMA, at 6 to 12 months FU, oral azithromycin given for 20 to 28 days to treat L. braziliensis infections in ACML probably reduces the likelihood of complete cure (RR 0.51, 95% CI 0.34 to 0.76; 2 RCTs, 93 participants; moderate-certainty evidence). Compared to intravenous MA (IVMA) and placebo, at 12 month FU, adding topical imiquimod to IVMA, given for 20 days to treat L. braziliensis, L. guyanensis and L. peruviana infections in ACL probably makes little to no difference to the likelihood of complete cure (RR 1.30, 95% CI 0.95 to 1.80; 1 RCT, 80 participants; moderate-certainty evidence). Compared to MA, at 6 months FU, one session of local thermotherapy to treat L. panamensis and L. braziliensis infections in ACL reduces the likelihood of complete cure (RR 0.80, 95% CI 0.68 to 0.95; 1 RCT, 292 participants; high-certainty evidence). Compared to IMMA and placebo, at 26 weeks FU, adding oral pentoxifylline to IMMA to treat CL (species not stated) probably makes little to no difference to the likelihood of complete cure (RR 0.86, 95% CI 0.63 to 1.18; 1 RCT, 70 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Evidence certainty was mostly moderate or low, due to methodological shortcomings, which precluded conclusive results. Overall, both IMMA and oral miltefosine probably result in an increase in cure rates, and nausea and vomiting are probably more common with miltefosine than with IMMA. Future trials should investigate interventions for mucosal leishmaniasis and evaluate recurrence rates of cutaneous leishmaniasis and its progression to mucosal disease.
Assuntos
Leishmaniose Cutânea/terapia , Administração Oral , Adulto , Antiprotozoários/administração & dosagem , Antiprotozoários/efeitos adversos , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Vacina BCG/uso terapêutico , Feminino , Humanos , Hipertermia Induzida , Imunocompetência , Injeções Intramusculares , Injeções Intravenosas , Interferon gama/uso terapêutico , Vacinas contra Leishmaniose/uso terapêutico , Leishmaniose Mucocutânea/terapia , Masculino , Antimoniato de Meglumina/administração & dosagem , Antimoniato de Meglumina/efeitos adversos , Pentoxifilina/administração & dosagem , Pentoxifilina/efeitos adversos , Fosforilcolina/administração & dosagem , Fosforilcolina/efeitos adversos , Fosforilcolina/análogos & derivados , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Pentoxifylline (PTX), an anti-hemorrhage drug used in the treatment of intermittent claudication, is extensively metabolized by the liver resulting in a reduction of the therapeutic levels within a short duration of time. Self-nano-emulsifying drug delivery system (SNEDDS) is well reported to enhance the bio-absorption of drugs by forming nano-sized globules upon contact with the biological fluids after oral administration. The present study aimed to formulate, characterize, and improve the oral bioavailability of PTX using SNEDDS. The formulated SNEDDS consisted of palm oil, Capmul® MCM, and Tween® 80 as oil, surfactant, and co-surfactant, respectively. The mixture design module under the umbrella of the design of experiments was used for the optimization of SNEDDS. The dynamic light-scattering technique was used to confirm the formation of nanoemulsion based on the globule size, in addition to the turbidity measurements. In vivo bioavailability studies were carried out on male Wistar rats. The pharmacokinetic parameters upon oral administration were calculated using the GastroPlus software. The optimized SNEDDS had a mean globule size of 165 nm with minimal turbidity in an aqueous medium. Bioavailability of PTX increased 1.5-folds (AUC = 1013.30 ng h/mL) as SNEDDS than the pure drug with an AUC of 673.10 ng h/mL. In conclusion, SNEDDS was seen to enhance the bioavailability of PTX and can be explored to effectively control the incidents of intermittent claudication.
Assuntos
Caprilatos/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Emulsificantes/farmacocinética , Glicerídeos/farmacocinética , Nanopartículas/metabolismo , Óleo de Palmeira/farmacocinética , Pentoxifilina/farmacocinética , Administração Oral , Animais , Disponibilidade Biológica , Caprilatos/administração & dosagem , Liberação Controlada de Fármacos , Emulsificantes/administração & dosagem , Glicerídeos/administração & dosagem , Masculino , Nanopartículas/administração & dosagem , Óleo de Palmeira/administração & dosagem , Tamanho da Partícula , Pentoxifilina/administração & dosagem , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/farmacocinética , Ratos , Ratos WistarRESUMO
While several published cases have reported tissue preservation with hyperbaric oxygen (HBO2) after frostbite, its routine use is not endorsed by expert consensus. We report a case of possible frostbite injury to the toes of both feet and the plantar surface of the left foot in a 17-year-old male patient. The exposure history included two episodes of rewarming followed by refreezing in the field during a hike through knee-deep snow without adequate clothing. The patient also sustained full-thickness ice abrasions to both anterior shins. The patient was evaluated within 60 minutes after self-rewarming. He was treated with 400 mg oral pentoxifylline three times a day and HBO2 at 2.4 atmospheres absolute for 90 minutes twice a day for a total of 13 treatments. Therapy was initiated approximately two hours from the estimated time of rewarming. Both feet recovered full sensation, and the patient had no tissue loss on his feet and and no functional impairment. The patient was followed for 12 months from injury. This case report highlights the difficulty health care providers face to accurately diagnose frostbite within the first 24 hours of injury, prior to development of more definitive signs and symptoms. Early treatment during this critical period may preserve tissue and function.
Assuntos
Congelamento das Extremidades/terapia , Oxigenoterapia Hiperbárica/métodos , Pentoxifilina/administração & dosagem , Vasodilatadores/administração & dosagem , Administração Oral , Adolescente , Terapia Combinada/métodos , Pé , Humanos , Masculino , Reaquecimento , Tempo para o Tratamento , Dedos do PéRESUMO
Dexamethasone has deleterious effects on male fertility and sperm parameters. In this study, the effect of dexamethasone on expression of CATSPER1 and 2 genes was investigated. These two genes play an important role in sperm motility. Selenium and pentoxifylline were subsequently used to protect testis tissue against the destructive effects of dexamethasone. Each group received one of the following treatments for 7 days: dexamethasone (7 mg/kg), pentoxifylline (200 mg/kg), selenium (0.3 mg/kg), dexamethasone + pentoxifylline or selenium + dexamethasone. Animals in the control group received a normal saline injection. The expression of CATSPER1 and 2 genes was analysed by real-time PCR and serum levels of FSH and LH were determined with the enzyme-linked immunosorbent assay method. Based on the results, dexamethasone decreases not only CATSPER1 and 2 gene expression but also serum levels of LH (p ≤ 0.05); however, it has no effect on FSH (p > 0.05). Treating with selenium significantly increased the gene expression of both CATSPER1 and 2 (p ≤ 0.05), while pentoxifylline enhanced only CATSPER2 gene expression (p ≤ 0.05). These two antioxidants were shown to increase serum levels of LH (p ≤ 0.05). Our data suggest that selenium is more effective than pentoxifylline in overcoming adverse effects of dexamethasone on male fertility.
Assuntos
Antioxidantes/administração & dosagem , Dexametasona/toxicidade , Infertilidade Masculina/prevenção & controle , Pentoxifilina/administração & dosagem , Selênio/administração & dosagem , Animais , Canais de Cálcio , Modelos Animais de Doenças , Hormônio Foliculoestimulante/sangue , Expressão Gênica/efeitos dos fármacos , Humanos , Infertilidade Masculina/induzido quimicamente , Injeções Intraperitoneais , Hormônio Luteinizante/sangue , Masculino , Camundongos , Proteínas de Plasma Seminal , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismoRESUMO
OBJECTIVE: To investigate the physical and chemical compatibility of pentoxifylline (PTX) with a wide range of parenteral medications used in the neonatal intensive care setting. DESIGN: PTX and drug solutions were combined in glass phials and inspected visually for physical incompatibility. The chemical compatibility was evaluated on the basis of PTX concentrations. RESULTS: Precipitation, colour change or turbidity was not visible in any of the test mixtures, indicating no observed physical incompatibility or apparent risk of blockage in narrow-bore intravenous tubing. The PTX concentration was approximately 2.5% and 4.5% lower when combined with dopamine and amoxicillin, respectively. The PTX concentration ratios for all other combinations were in the range of 99%-102%. CONCLUSION: In simulated Y-site conditions, physical compatibility testing of PTX and 30 parenteral medications revealed no evidence of precipitation. Based on PTX concentration tests, it could be prudent to avoid mixing PTX with dopamine or amoxicillin.
Assuntos
Pentoxifilina/química , Inibidores de Fosfodiesterase/química , Administração Intravenosa , Incompatibilidade de Medicamentos , Interações Medicamentosas/fisiologia , Quimioterapia Combinada , Humanos , Lactente , Recém-Nascido , Pentoxifilina/administração & dosagem , Inibidores de Fosfodiesterase/administração & dosagemRESUMO
AIM: Present study was designed to evaluate protective effects of pentoxifylline and its potentiation with low dose of nitric oxide (NO) modulators in adjuvant-induced experimental arthritis in rats. METHOD: Wistar rats (200-300 g, n = 8 per group) of both sexes were used in the study. On day "0" experimental arthritis was induced by injecting 0.2 ml of Complete Freund's adjuvant (CFA) in sub-planter region of right hind paw of animals. Pentoxifylline treatment alone and in combination with NO modulators was given (i.p.) from day 14 to 28. Various arthritic parameters were recorded and blood and joint synovial fluid was collected for biochemical analysis. RESULTS: CFA inoculation significantly increases (1) arthritic index (2) ankle diameter (3) paw volume (4) histopathology score (5) serum TNF-α, IL-6, IL-1ß and synovial TNF-α levels (p < 0.001) (6) serum Th1 and Th2 cytokine levels g) MDA levels in rat paw tissue homogenates (7) serum NF-κB levels. Significant decrease in serum IL-10 levels and SOD activity was observed in rats after CFA inoculation. Decrease in body weight and suppressed general quality of life of CFA inoculated rats was also observed. These CFA-induced arthritic changes were significantly reversed by pentoxifylline alone and in combination with low dose of NO modulators (p < 0.05). CONCLUSION: These results are suggestive of protective effects of pentoxifylline and its potentiation in combination with low dose of NO modulators. These results may provide new pharmacological therapy for management of rheumatoid arthritis (RA).
Assuntos
Anti-Inflamatórios/administração & dosagem , Artrite Experimental/metabolismo , Fatores Imunológicos/administração & dosagem , Mediadores da Inflamação/metabolismo , Óxido Nítrico/metabolismo , Pentoxifilina/administração & dosagem , Animais , Artrite Experimental/tratamento farmacológico , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Masculino , NG-Nitroarginina Metil Éster/administração & dosagem , Óxido Nítrico/antagonistas & inibidores , Ratos , Ratos WistarRESUMO
BACKGROUND: The combination of pentoxifylline (Trental) and vitamin E has been reported to reverse significant consequences of radiation after mastectomy with immediate reconstruction, such as severe capsular contracture or loss of implants. We questioned whether prophylactic use could prevent these consequences. METHODS: Thirty women with implants or tissue expanders after mastectomy that underwent adjuvant radiation were treated with Trental and vitamin E for 180 days. All subjects then entered a 12-month observational phase. RESULTS: Of the 26 evaluable subjects, 3 subjects required implant revisions. One due to malposition of the nonradiated breast and 2 were due to contracture (7.7%). There were no implant losses. CONCLUSIONS: The combination of Trental and vitamin E can prevent severe contracture and implant losses allowing for immediate reconstruction with implant or tissue expander even if radiation is planned after mastectomy.
Assuntos
Implante Mamário/efeitos adversos , Neoplasias da Mama/radioterapia , Contratura Capsular em Implantes/prevenção & controle , Mastectomia/métodos , Pentoxifilina/administração & dosagem , Vitamina E/administração & dosagem , Adulto , Implante Mamário/métodos , Implantes de Mama/efeitos adversos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Estudos de Coortes , Quimioterapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , Estudos Prospectivos , Radioterapia Adjuvante , Medição de Risco , Resultado do TratamentoRESUMO
INTRODUCTION: The treatment of leishmaniasis ischallenging, given the difficulties in drug administration and resistance. Therefore, we chose to test the efficacy of miltefosine combined with pentoxifylline. METHODS: Twenty-seven isogenic C57Bl/6 mice were infected with Leishmania (Leishmania) amazonensis, and equally divided into three groups: miltefosine (200mg/kg/day), miltefosine (200mg/kg/day) with pentoxifylline (8mg/kg/day), and untreated. Response to treatment was evaluated using paw diameter and parasitological criteria. RESULTS: The number of viable Leishmania reduced significantly within the miltefosine-pentoxifylline group (p < 0.05). CONCLUSIONS: There is hope that a viable treatment exists for Leishmania infection.
Assuntos
Antiprotozoários/administração & dosagem , Leishmaniose Cutânea/tratamento farmacológico , Pentoxifilina/administração & dosagem , Fosforilcolina/análogos & derivados , Administração Oral , Animais , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Camundongos Endogâmicos C57BL , Fosforilcolina/administração & dosagem , Fatores de TempoRESUMO
Severe alcoholic hepatitis is still associated with high mortality and presence of liver failure manifested by jaundice, coagulopathy and encephalopathy is a poor prognostic indicator. The management of these patients includes at first hand several supportive measures as treatment of alcohol withdrawal, administration of fluid and vitamins and admission to an intensive care unit in the unstable patient. Glucocorticoids have been since decades the most intensively studied therapy in alcoholic hepatitis and are effective in certain subgroups. Indication for such a therapy is usually defined on a Maddrey Discriminant Function > 32. The Lille score at day 7 is used to decide whether corticosteroid therapy should be stopped or continued for a 1 month course. Nutritional supplementation is also likely to be beneficial. The main progress in better understanding its pathophysiology has come from cytokine studies. Various proinflammatory cytokines such as tumor necrosis factor-alpha (TNFα) or interleukin-1 (IL-1) have been proposed to play a role in this disease. This advancement has recently led to pilot studies investigating anti-TNF drugs such as pentoxifylline, infliximab (anti-TNF antibody) or etanercept in the treatment of this disease. These studies revealed besides for pentoxifylline rather negative results. Despite this fact, targeting of certain cytokines such as IL-1 remains an attractive treatment concept for this devastating disorder in the future.
Assuntos
Hepatite Alcoólica/reabilitação , Alcoolismo/fisiopatologia , Alcoolismo/reabilitação , Anticorpos Monoclonais/administração & dosagem , Terapia Combinada , Etanercepte , Fígado Gorduroso Alcoólico/diagnóstico , Fígado Gorduroso Alcoólico/fisiopatologia , Fígado Gorduroso Alcoólico/reabilitação , Hidratação , Glucocorticoides/administração & dosagem , Hepatite Alcoólica/diagnóstico , Hepatite Alcoólica/fisiopatologia , Humanos , Imunoglobulina G/administração & dosagem , Infliximab , Unidades de Terapia Intensiva , Interleucina-1/sangue , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/fisiopatologia , Falência Hepática Aguda/reabilitação , Testes de Função Hepática , Transplante de Fígado , Seleção de Pacientes , Pentoxifilina/administração & dosagem , Projetos Piloto , Prognóstico , Receptores do Fator de Necrose Tumoral/administração & dosagem , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/sangue , Vitaminas/administração & dosagemRESUMO
The microvascular bed is an anatomical entity which comprises myriads of small arterioles, capillaries and venules. Microvessels and surrounding tissue metabolism are tightly coupled; consequently they are equipped with many, very specific and fine-tuned mechanisms allowing permanent, precise regulation of nutrient delivery. The review thoroughly describes the structure and physiology of arterioles and capillaries as well as the specialized means to investigate them. Microcirculation has been largely neglected for decades, mainly because of lack of technical possibilities for visualization and quantitation. However the past years have completely renewed the scientific interest, due to the combination of the availability of new techniques in human research and the recognition that the microcirculation is autonomically and causally involved in diseases previously thought to be essentially a question of macrocirculation. Today we start to see that microangiopathy is not only a consequence of large vessel diseases but can be the source of many pathologies in both cardiovascular and metabolic disorders, the best example -developed here- being the cardiometabolic syndrome or prediabetes. With very few exceptions, pentoxifylline and the antidiabetic metformin, no specific treatments have been developed for treating disorders at the microcirculatory level. Metformin has unique, intrinsic actions specifically at the level of terminal arterioles, which are completely independent of its antidiabetic effect. Other drugs are shortly described which have revealed a potential interest in this field. Our review aims at showing that microcirculation is entering a new era, starting with rapidly increasing knowledge of its intimate functioning and worth specific pharmacological developments.
Assuntos
Hemorreologia/efeitos dos fármacos , Microcirculação/efeitos dos fármacos , Microvasos , Doenças Vasculares , Angiopatias Diabéticas/tratamento farmacológico , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/patologia , Hemorreologia/fisiologia , Humanos , Metformina/administração & dosagem , Metformina/farmacologia , Metformina/uso terapêutico , Microcirculação/fisiologia , Microvasos/efeitos dos fármacos , Microvasos/patologia , Microvasos/fisiologia , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/patologia , Pentoxifilina/administração & dosagem , Pentoxifilina/farmacologia , Pentoxifilina/uso terapêutico , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/etiologia , Doenças Vasculares/patologia , Vasodilatadores/administração & dosagem , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêuticoAssuntos
Circuncisão Masculina/efeitos adversos , Oxigenoterapia Hiperbárica , Isquemia/terapia , Pênis/irrigação sanguínea , Pentoxifilina/uso terapêutico , Vasodilatadores/uso terapêutico , Pré-Escolar , Terapia Combinada , Humanos , Infusões Intravenosas , Isquemia/tratamento farmacológico , Isquemia/etiologia , Masculino , Necrose , Oxigênio/farmacocinética , Pênis/patologia , Pentoxifilina/administração & dosagem , Vasodilatadores/administração & dosagemRESUMO
Non-surgical treatment of Peyronie's disease (PD) has come a long way since it was first described in 1743. A myriad of treatment options are currently available, including oral, intralesional and external energy therapies. The purpose of this article is to review the contemporary literature on non-surgical therapies for PD, and where possible, focus on randomized, placebo-controlled trials, as well as review the latest guidelines for the management of PD from the International Committee on Sexual Medicine, which conveyed its findings in July 2009. At this time, it appears that a combination of oral agents and/or intralesional injection with traction therapy may provide a synergy between the chemical effects of the drugs and the mechanical effects of traction. Until a reliable treatment emerges, it does appear that some of the non-surgical treatments discussed can be used to stabilize the scarring process and may result in some reduction of deformity with improved sexual function.
Assuntos
Induração Peniana/terapia , Administração Oral , Corticosteroides/administração & dosagem , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/efeitos adversos , Colagenases/administração & dosagem , Colagenases/efeitos adversos , Terapia por Estimulação Elétrica , Humanos , Injeções Intralesionais , Iontoforese , Masculino , Induração Peniana/tratamento farmacológico , Induração Peniana/patologia , Pênis/efeitos dos fármacos , Pênis/patologia , Pentoxifilina/administração & dosagem , Pentoxifilina/efeitos adversos , Inibidores de Fosfodiesterase/administração & dosagem , Placebos , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , TraçãoRESUMO
The main basic effect of hyperbaric oxygenation (HBO2) on the human body, in our study, was an increased partial pressure of oxygen resulting from an increased amount of oxygen dissolved in plasma. Thus the plasma can become capable of carrying enough oxygen to meet the needs of the body's tissues. From 1 January 2004 to 31 December 2007, a total of 61 patients (62 ears) received medical treatment at the ENT clinic of the 3rd Faculty of Medicine, Charles University, and at the Central Military Hospital in Prague. Treatment consisted of a combination of vasodilatation infusion treatment and HBO2 therapy. The results were evaluated in a retrospective study. The overall percentage of patients showing improvement was 59.7%. However, for those patients who started HBO2 treatment within 10 days of onset, complete recovery, or significant improvement was noted in 65.9%. In contrast, patients who started treatment after 10 days of onset, improvement was noted in only 38.9%. NMR examination revealed that two patients had vestibular schwannoma (also known as acoustic neuroma).
Assuntos
Perda Auditiva Neurossensorial/terapia , Perda Auditiva Súbita/terapia , Oxigenoterapia Hiperbárica/métodos , Oxigênio/sangue , Vasodilatadores/administração & dosagem , Adulto , Idoso , Audiometria , Terapia Combinada/métodos , Feminino , Glucocorticoides/administração & dosagem , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Súbita/etiologia , Humanos , Masculino , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Pressão Parcial , Pentoxifilina/administração & dosagem , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Vasodilatação , Alcaloides de Vinca/administração & dosagem , Adulto JovemRESUMO
A method for the treatment of chronic sensorineural hearing loss (CSNHL) is proposed that includes administration of trental followed by intravenous laser irradiation of blood (IVLBI). The study included 81 patients at the age from 20 to more than 60 years presenting with CSNHL. They were allocated to three groups; the patients in group 1 (n=32) were given trental intravenously followed by intravenous laser irradiation of blood, those of group 2 (n=24) were treated with IVLBI alone while patients of group 3 (n=25) received "traditional" treatment. Audiometric examination and rheoencephalography were carried out before and after therapy. The hearing improved to 18-20 dB in group 1, to 10-15 dB in group 2, and to 10 dB in group 3. The improvement of rheoencephalographic characteristics was documented in the patients of all groups but was especially pronounced in group 1. It is concluded that the proposed method significantly increases the efficiency of treatment of chronic sensorineural hearing loss.
Assuntos
Sangue/efeitos da radiação , Perda Auditiva Neurossensorial/terapia , Audição/fisiologia , Terapia com Luz de Baixa Intensidade/métodos , Pentoxifilina/administração & dosagem , Adulto , Audiometria , Doença Crônica , Feminino , Audição/efeitos dos fármacos , Perda Auditiva Neurossensorial/fisiopatologia , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vasodilatadores/administração & dosagem , Adulto JovemRESUMO
INTRODUCTION: Breast-conserving therapy is currently the standard of management of breast cancer cases. Radiotherapy is an integral part of it; however, it has several complications. Radiation induced burn is a common complication of radiotherapy that requires more effective lines of management rather than the classically used ones. We investigated whether the addition of pentoxifylline (PTX) alone or in combination with topical honey is effective in its management compared to the standard measures. METHODS AND MATERIALS: In this prospective study, patients were randomly allocated into three groups each of 50 cases. Group A received standard burn treatment (control group). Group B received additionally 400 mg PTX twice daily. Group C received the same treatment as Group B with adding topical purified honey ointment. Patients were assessed initially and subsequently after 4 and 12 weeks, for projected coetaneous surface area (PCSA) of burn, pain severity, limitation of movement and exudation. RESULTS: There was a striking regression of the mean PCSAs of lesions among groups B and C at 12 weeks, with reduction rates (86±61%) and (76±58%) respectively (p<0.0001***). The addition of honey was associated with marked pain relieving effect and rescue of proper motion. Finally, honey was associated with shorter duration of treatment as 74% of group C patients completely recovered after 12 weeks, compared to only 54% and 36% of groups B and A in order. CONCLUSION: Combination of PTX and honey is an ideal measure for treatment of radiation-induced burn following breast conservative surgery.
Assuntos
Neoplasias da Mama/radioterapia , Mel , Mastectomia Segmentar , Pentoxifilina/uso terapêutico , Lesões por Radiação/tratamento farmacológico , Protetores contra Radiação/uso terapêutico , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Quimioterapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Pentoxifilina/administração & dosagem , Estudos Prospectivos , Lesões por Radiação/patologia , Protetores contra Radiação/administração & dosagemRESUMO
The article describes a positive effect of adjuvant therapy (diet therapy, tsitrarginin, trental) on regression of fatty liver disease, inflammation and prevention of liver fibrosis through influence on the system of L-arginine-NO, exchange of collagen proteins, anti-inflammatory cytokines in patients with steatohepatitis and second type diabetes mellitus.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Arginina/uso terapêutico , Fígado Gorduroso/terapia , Cirrose Hepática/prevenção & controle , Fígado/efeitos dos fármacos , Doadores de Óxido Nítrico/uso terapêutico , Pentoxifilina/uso terapêutico , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Arginina/administração & dosagem , Terapia Combinada , Quimioterapia Combinada , Fígado Gorduroso/complicações , Fígado Gorduroso/dietoterapia , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/imunologia , Humanos , Interleucina-1/imunologia , Interleucina-10/imunologia , Fígado/enzimologia , Fígado/metabolismo , Testes de Função Hepática , Pessoa de Meia-Idade , Doadores de Óxido Nítrico/administração & dosagem , Pentoxifilina/administração & dosagemRESUMO
Measures to suppress inflammatory reactions are taken to prevent fibrous encapsulation of implants. It is proposed in this study that tissue engineered scaffolds that can slowly release anti-inflammatory drugs can help reduce inflammatory reactions around implants. Chitosan and chitosan cross-linked with different concentrations of pectin were made into films and porous scaffolds. Results seen from Fourier-transform infrared spectra and thermal gravimetric analysis showed that polyelectrolyte complexation took place between chitosan and pectin units. As the amounts of pectin added to chitosan increased (0%, 0.5%, 1%, and 2%) the scaffolds became more wettable (contact angle decreased from 81 degrees to 76 degrees ), less swellable (swelling ratio decreased from 35% to 30%), and less capable of releasing pentoxifylline (PTX) (release efficacies decreased from 93% to 83%). Higher degrees of pectin cross-linking made the scaffolds more resistant to compression (Young's modulus increased from 2.4 kPa to 3.7 kPa) and more favorable for initial cell attachment (percentage of attached cells increased from 55% to 67%). In vitro tests showed that, with the reduction of PTX release rates, PTX became more effective in inhibiting TNF-alpha and IL-6 production from activated macrophages. This investigation has demonstrated that the changes in the basic drug release properties of chitosan scaffolds were proportional to the amount of pectin added. The changes could help improve the effectiveness of PTX.