Systemic Pentoxifylline Research Articles

The Preventive Effect of Systemic Honokiol and Systemic Pentoxifylline on Epidural Fibrosis.

To investigate the preventive effects of systemic honokiol and pentoxifylline treatments on epidural fibrosis (EF) in the experimental laminectomy model. Thirty-two rats were divided into four equal groups. Laminectomy was performed in all rats except for the control group. One group was kept as the negative control group. Moreover, 10 mg/kg pentoxifylline and 10 mg/kg honokiol were administered intraperitoneally for 5 days, respectively, to the other two groups. The rats were sacrificed after 4 weeks. The samples were examined biochemically in terms of oxidative stress and inflammation induced by tissue damage. Histopathological and immunohistochemical investigations were also performed to detect EF severity. In honokiol and pentoxifylline groups compared with the negative control group, tumor necrosis factor-beta and interleukin-10 levels (indicating inflammation); myeloperoxidase, malondialdehyde, and hydroxyproline levels (indicating oxidative stress); and intercellular adhesion molecule levels (indicating fibrosis) were decreased. Histopathologically and immunohistochemically, EF was significantly reduced in the pentoxifylline and honokiol groups. Biochemical findings were consistent with the histopathological and immunohistochemical findings. Both pentoxifylline and honokiol prevent EF formation. However, this effect is more pronounced in honokiol.

Pentoxifylline Inhibits Epidural Fibrosis in Post-Laminectomy Rats.

BackgroundThe aim of this experimental study was to investigate the effectiveness of intramuscular pentoxifylline in the prevention of postoperative fibrosis.Material/MethodsWe divided 16 adult Wistar albino rats into 2 equal groups: treatment and control. Both groups underwent L1 vertebral total laminectomy to expose the dura. The intramuscular treatment group received pentoxifylline. Four weeks later, epidural fibrosis was studied in both groups using electron microscopy, light microscopy, histology, biochemistry, and macroscopy.ResultsThe evaluation of epidural fibrosis in the 2 groups according to macroscopic (p<0.01) assessment and light microscopy revealed that epidural scar tissue formation was lower in the treatment group compared to the control group (p<0.001) and the number of fibroblasts was also decreased significantly in the pentoxifylline-treated group (p<0.05). More immature fibers were demonstrated in the treatment group by electron microscopy in comparison with the control group. In biochemical analysis, a statistically significant decrease was detected in hydroxyproline, which indicates fibrosis and myeloperoxidase activity, and shows an inflammatory response (P<0.001).ConclusionsSystemic pentoxifylline application prevents postoperative epidural fibrosis and adhesions with various mechanisms. Our study is the first to present evidence of experimental epidural fibrosis prevention with pentoxifylline.

Nebulized Pentoxifylline for Reducing the Duration of Oxygen Supplementation in Extremely Preterm Neonates

To evaluate the efficacy and safety of nebulized pentoxifylline for reducing the duration of oxygen supplementation in extremely preterm neonates at high risk of bronchopulmonary dysplasia (BPD). Single-center, randomized, double-blind, placebo-controlled trial was conducted. Infants of 23(0) to 27(6) weeks' gestational age requiring mechanical ventilation or ≥30% supplemental oxygen on continuous positive airway pressure at 72-168 hours were randomized to receive 20 mg/kg (1 mL/kg) nebulized pentoxifylline or an equal volume of normal saline placebo every 6 hours for 10 consecutive days via a vibrating mesh nebulizer. The primary outcome was the duration of oxygen supplementation at 40 weeks' postmenstrual age. We used Cox proportional hazards regression modeling to analyze outcomes. All infants had adequate data for analysis of the primary outcome. Intention-to-treat analysis revealed no differences in duration of oxygen supplementation at 40 weeks' postmenstrual age between pentoxifylline (n=41) and placebo (n=40) groups (median 2262 vs 2160 hours, adjusted hazard ratio: 1.14, 95% CI 0.72-1.80, P=.63). There was no difference in mortality and further secondary outcomes. No adverse effects were noted. Nebulized pentoxifylline is safe but did not reduce the duration of oxygen supplementation in extremely preterm infants at high risk of BPD. Dose-ranging studies and large, well-designed clinical trials are required to determine whether the use of nebulized or systemic pentoxifylline as a prophylactic therapy offers small but relevant benefits for prevention of BPD. Australian New Zealand Clinical Trials Registry: ACTRN12611000145909.

Systematic review of miscellaneous agents for the management of oral mucositis in cancer patients

The aim of this systematic review was to analyze the available literature and define clinical practice guidelines for the use of the following agents for the prevention and treatment of oral mucositis (OM): allopurinol, midline mucosa-sparing radiation blocks, payayor, pentoxifylline, timing of radiation therapy (RT) (morning versus late afternoon), pilocarpine, bethanechol, chewing gum, propantheline, and tetrachlorodecaoxide. A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, no guideline possible. A total of 32 papers across 10 interventions were examined. New suggestions were developed against the use of systemic pilocarpine administered orally for prevention of OM during RT in head and neck cancer patients and in patients receiving high-dose chemotherapy, with or without total body irradiation, prior to hematopoietic stem cell transplantation. A suggestion was also made against the use of systemic pentoxifylline administered orally for the prevention of OM in patients undergoing bone marrow transplantation. No guideline was possible for any other agent reviewed due to inadequate and/or conflicting evidence. None of the agents reviewed was determined to be effective for the prevention or treatment of OM. Two agents, pilocarpine and pentoxifylline, were determined to be ineffective, in the populations listed above. Additional well-designed research is needed on other interventions.

Nephrogenic systemic fibrosis in advanced chronic kidney disease: A single hospital’s experience in Taiwan

Nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD) clinically resembles scleromyxedema which develops in the setting of advanced chronic kidney diseases. Limited data exist about its epidemiology in Asian countries. A total of 153 magnetic resonance imaging (MRI) examinations, including 81 contrast-enhancement, were identified in 127 patients with advanced chronic kidney disease at stage five undergoing MRI or angiography examination between January 2005 and July 2007, in our hospital. The diagnosis of NFD/NSF was established based on clinical manifestation and histopathology. NFD/NSF was diagnosed in none of the 105 patients on haemodialysis but in one of the 22 patients on peritoneal dialysis. This 24-year-old woman was a case of systemic lupus erythematosus since age 15 and who developed skin lesions two months before the initiation of peritoneal dialysis but nine months after four exposures to gadodiamide during MRI study. The skin condition had significantly improved within three months under a combination regimen of systemic pentoxifylline and topical clobetasol propionate ointment, with further amelioration during subsequent treatment with colchicine. Our results lend support to the predisposition of gadolinium-containing contrast agents to the development of NFD/NSF in patients with advanced renal failure, even before the initiation of dialysis. The cause of a lower incidence rate in our series remains to be determined.

Systemic pentoxifylline decreases mortality in severe burn patients with inhalation injury: Preliminary report of a randomized controlled trial

Systemic pentoxifylline decreases mortality in severe burn patients with inhalation injury: Preliminary report of a randomized controlled trial

Intraarterial pulmonary pentoxifylline improves cardiac performance and oxygen utilization after hemorrhagic shock: a novel resuscitation strategy.

The role of pentoxifylline (PTX) as a resuscitation adjunct in hemorrhagic shock is unclear. PTX infusion into the pulmonary artery and its effects on cardiac performance and oxygen utilization have not been defined. We hypothesized that pulmonary PTX is superior to systemic PTX or lactated Ringer's (LR) solution alone. The effects of LR solution, systemic PTX, and pulmonary PTX on cardiac performance and oxygen utilization in a hemorrhagic shock model in dogs were compared. Animals were bled to a mean arterial blood pressure (MAP) of 40 mm Hg maintained for 30 min and randomized into 3 resuscitation groups: LR solution (2x shed blood), systemic PTX (10 mg/kg bolus i.v.) in addition to LR solution (2x shed blood) + PTX (5 mg/kg for 45 min i.v.), and pulmonary PTX (10 mg/kg bolus + 5 mg/kg for 45 min via a pulmonary artery catheter) plus LR solution (2x shed blood, i.v.). Arterial blood gases, hemoglobin levels, MAP, cardiac index, systemic vascular resistance index, pulmonary vascular resistance index, oxygen delivery, oxygen consumption, and oxygen extraction ratio (O(2)ER) were measured serially. No differences in blood loss, hemoglobin, and MAP were observed. Pulmonary PTX increased cardiac index to levels more than baseline (P = 0.012) and decreased systemic vascular resistance index and pulmonary vascular resistance index to levels less than baseline (P < 0.0001). Pulmonary PTX increased oxygen delivery and oxygen consumption to baseline levels. Postresuscitation O(2)ER levels in LR-treated animals remained more than baseline (P < 0.0001). Systemic and pulmonary PTX significantly decreased O(2)ER compared with shock levels. PTX resuscitation is superior compared with LR solution alone. Intraarterial pulmonary PTX administration is safe, and improves cardiac performance as well as O(2) utilization. This study shows that a novel route (via the pulmonary circulation) used to administer pentoxifylline after hemorrhagic shock leads to superior cardiac performance in comparison with administration via lactated Ringer's solution or i.v. systemic pentoxifylline.

The effect of pentoxifylline on the healing of full-thickness skin defects of diabetic and normal rats

In this paper, the effects of systemic pentoxifylline administration on normal and diabetic wound healing are studied. Twenty-four normoglycemic and 24 diabetic rats were compared, exploring the healing of standardized (15×15 mm) full-thickness wounds by secondary intention. Twelve rats of both groups received intraperitoneal pentoxifylline 10 mg/kg per day. The strength of the healed tissues was evaluated by straining tests, the healing time of each wound was recorded, and the healed tissues were examined histologically. In the diabetic group, the only significant difference between the rats receiving pentoxifylline and the others was the shortened healing time. Pentoxifylline significantly reduced the time needed for complete epithelization and also increased the tensile strength significantly in normoglycemic rats. As expected, significant differences were recorded between the normoglycemic and diabetic rats regarding healing time and scar tissue strength. In conclusion, systemic pentoxifylline administration may be helpful in shortening the healing time of full-thickness wounds both in diabetic and normoglycemic patients, and it can increase the tensile strength of the healed wound in normoglycemic organisms.

Ocular toxicology.

This review of recent articles on ocular toxicology concentrates on undesirable effects on the eye induced by systemically used xenobiotics. These include color vision deficiencies or visual field deterioration related to antiepileptic drugs, elevated intraocular pressure associated with inhaled corticosteroids, retinal detachments associated with systemic corticosteroids, rifabutin-induced uveitis, cocaine-related retinal hemorrhagic lesions in utero, deferoxamine-related decreases in vision, ocular allergy to bovine-derived collagen, and a large case study of hydroxychloroquine retinotoxicity. Other publications reviewed include a controlled study showing that glucose levels do not seem to alter color vision, a report that intravenous methotrexate can reach clinically meaningful levels in the aqueous humor, and a study showing the effect of systemic pentoxifylline on ocular blood flow and diabetes. With respect to systemic effects of topical ocular medications, there was a case report of apparent systemic exposure to pilocarpine from an Ocusert (Alza Corp., Palo Alto, CA), generalized urticaria after a single application of 1% cyclopentolate, and asthma induced with topical ketorolac. Readers are reminded that no drug achieves ultimate efficacy or ultimate safety. Thus, the decision to employ a given therapy involves a physician's evaluation of its therapeutic index, that is, the ratio between efficacy and toxicity.

Systemic anti-tumor necrosis factor antibody treatment exacerbates endotoxin-induced uveitis in the rat

Tumor necrosis factor is released in the circulation and aqueous humor during endotoxin-induced uveitis, and induces acute uveitis when injected intraocularly in rats. To elucidate the role of tumor necrosis factor in the development of endotoxin-induced uveitis we analysed the effect of neutralizing anti-tumor necrosis factor antibodies and of pentoxifylline, a drug that inhibits tumor necrosis factor synthesis. Lewis rats were treated with: (a) a single intracardial injection of polyclonal rabbit anti-murine tumor necrosis factor antiserum prior to foot pad injection of 200 micrograms lipopolysaccharide; (b) an intraperitoneal injection of 10 mg pentoxifylline 1 hr before, at the time of, and 3 hr after foot pad injection of lipopolysaccharide; or (c) an intravitreal injection of 20 to 500 micrograms pentoxifylline together with 1 microgram lipopolysaccharide. The ocular inflammation was examined by slit-lamp and evaluated for the presence of hyperemia, flare, miosis, infiltrating cells or hypopyon. Levels of tumor necrosis factor in serum and aqueous samples were determined using a bioassay. Systemic treatment with either anti-tumor necrosis factor antibodies or pentoxifylline resulted in a significant inhibition, 90 and 70% respectively, of serum tumor necrosis factor activity at 3 to 4 hr after lipopolysaccharide injection. Systemic pentoxifylline treatment had no influence on the severity of uveitis. Anti-tumor necrosis factor antibody treatment, in contrast, caused an exacerbation of endotoxin-induced uveitis at t = 20 hr; mean uveitis score 3.9 vs. 1.4 in controls; P < 0.01. Intraocular administration of pentoxifylline together with lipopolysaccharide also had an aggravating effect on uveitis, that was associated with increased levels of intraocular tumor necrosis factor. The results show that inhibition of serum tumor necrosis factor activity does not block the development of endotoxin-induced uveitis. In fact, anti-tumor necrosis factor antibody treatment exacerbates the intraocular inflammation. These findings suggest that tumor necrosis factor may have other than proinflammatory properties in this uveitis model.