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American Journal of Physiology. Heart... Mar 2024Pentoxifylline is a nonselective phosphodiesterase inhibitor used for the treatment of peripheral artery disease. Pentoxifylline acts through cyclic adenosine... (Randomized Controlled Trial)
Randomized Controlled Trial
Pentoxifylline is a nonselective phosphodiesterase inhibitor used for the treatment of peripheral artery disease. Pentoxifylline acts through cyclic adenosine monophosphate, thereby enhancing red blood cell deformability, causing vasodilation and decreasing inflammation, and potentially stimulating ventilation. We conducted a double-blind, placebo-controlled, crossover, counter-balanced study to test the hypothesis that pentoxifylline could lower blood viscosity, enhance cerebral blood flow, and decrease pulmonary artery pressure in lowlanders following 11-14 days at 3,800 m. Participants (6 males/10 females; age, 27 ± 4 yr old) received either a placebo or 400 mg of pentoxifylline orally the night before and again 2 h before testing. We assessed arterial blood gases, venous hemorheology (blood viscosity, red blood cell deformability, and aggregation), and inflammation (TNF-α) in room air (end-tidal oxygen partial pressure, ∼52 mmHg). Global cerebral blood flow (gCBF), ventilation, and pulmonary artery systolic pressure (PASP) were measured in room air and again after 8-10 min of isocapnic hypoxia (end-tidal oxygen partial pressure, 40 mmHg). Pentoxifylline did not alter arterial blood gases, TNF-α, or hemorheology compared with placebo. Pentoxifylline did not affect gCBF or ventilation during room air or isocapnic hypoxia compared with placebo. However, in females, PASP was reduced with pentoxifylline during room air (placebo, 19 ± 3; pentoxifylline, 16 ± 3 mmHg; = 0.021) and isocapnic hypoxia (placebo, 22 ± 5; pentoxifylline, 20 ± 4 mmHg; = 0.029), but not in males. Acute pentoxifylline administration in lowlanders at 3,800 m had no impact on arterial blood gases, hemorheology, inflammation, gCBF, or ventilation. Unexpectedly, however, pentoxifylline reduced PASP in female participants, indicating a potential effect of sex on the pulmonary vascular responses to pentoxifylline. We conducted a double-blind, placebo-controlled study on the rheological, cardiorespiratory and cerebrovascular effects of acute pentoxifylline in healthy lowlanders after 11-14 days at 3,800 m. Although red blood cell deformability was reduced and blood viscosity increased compared with low altitude, acute pentoxifylline administration had no impact on arterial blood gases, hemorheology, inflammation, cerebral blood flow, or ventilation. Pentoxifylline decreased pulmonary artery systolic pressure in female, but not male, participants.
Topics: Male; Humans; Female; Young Adult; Adult; Pentoxifylline; Hemorheology; Tumor Necrosis Factor-alpha; Hypoxia; Oxygen; Acclimatization; Inflammation; Gases; Cerebrovascular Circulation; Altitude
PubMed: 38241007
DOI: 10.1152/ajpheart.00783.2023 -
International Journal of Dermatology Mar 2024
Topics: Humans; Necrobiosis Lipoidica; Pentoxifylline; Diabetes Mellitus, Type 1
PubMed: 38238633
DOI: 10.1111/ijd.17037 -
Cureus Dec 2023In this report, we present the clinical management of a male patient diagnosed with non-obstructive azoospermia (NOA), a condition characterized by the absence of sperm...
In this report, we present the clinical management of a male patient diagnosed with non-obstructive azoospermia (NOA), a condition characterized by the absence of sperm in the ejaculate due to impaired spermatogenesis. A 37-year-old patient underwent two surgical procedures: testicular sperm aspiration (TESA) and percutaneous epididymal sperm aspiration (PESA). Surprisingly, the beta-human chorionic gonadotropins (β-HCG) testing that followed produced promising findings suggesting NOA syndrome may be reversible. Theophylline and pentoxifylline, phosphodiesterase inhibitors with immunomodulatory effects, were creatively used in this case study to increase sperm viability and activation after PESA. Hyaluronic acid was also used as an additional therapy because it is well known for aiding in sperm development and binding to oocytes. The patient underwent hyaluronic acid, which can potentially increase the fertilization rate and improve the selection of sperm. This in-depth case study offers insightful information on the effective management of NOA by combining theophylline, pentoxifylline, and hyaluronic acid. The results highlight the ability of these therapies to revive spermatogenesis, offering a cutting-edge method of treating male infertility. More research is required to clarify the underlying processes and confirm the effectiveness of this strategy in more successful reproductive medicine therapies.
PubMed: 38226124
DOI: 10.7759/cureus.50623 -
Journal of the Mechanical Behavior of... Mar 2024A bio-implant is a drug-delivery system that is implanted in the human body for a period of more than 30 days. Electromechanical systems are one type of bio-implant that...
INTRODUCTION
A bio-implant is a drug-delivery system that is implanted in the human body for a period of more than 30 days. Electromechanical systems are one type of bio-implant that has recently been introduced as a new generation of targeted drug delivery methods. The overarching goal of utilizing these systems is to integrate electrical and mechanical features in order to benefit from the numerous applications of these two systems when used together. The current study aimed to design a prototype of an electromechanical system using Fused Deposition Modeling (FDM), Selective Laser Sintering (SLS), and MultiJet Fusion (MJF) techniques for drug delivery that can release a specific drug dosage in the patient's body by connecting to a sensor or under the control of a signal sent by the physician.
METHODS
Initially, the implant chambers were created in the form of a hollow cylinder, closed at one end, using three different types of 3D printers: FDM, SLS, and MJF. Each implant was then filled with a model drug (pentoxifylline) and sealed with a thin gold membrane. To achieve the lowest voltage required to melt the gold membrane, an electric circuit with controllable DC voltage generator was designed. Finally, the mechanical resistance, drug release rate, and surface morphology of the designed implants were evaluated.
RESULTS
The MJF 3D printer, overally, had higher printing precision and repeatability than other printers; however, the implants printed by the FDM 3D printer were more accurate than other techniques (P value < 0.001), similar to the dimensions of the designed file. The mechanical resistance of the implants was also evaluated, and the polylactic acid implants printed by FDM had the highest value of Young's modulus in both the standard samples and the designed implants. During the 3-month drug leakage study, FDM 3D printed implant had a greater ability to store the desired drug load (P value < 0.001), Furthermore, the SEM micrographs revealed that the polylactic acid implants printed by FDM had minimal porosity in their structure and the layers were well adhered together. The gold membrane with a middle diameter of 2 mm required the lowest voltage of 6 V. As a result, the final electrical circuit was designed with smaller dimensions in order to achieve the voltage required to melt the gold membrane.
CONCLUSION
Due to the lack of drug leakage and other mechanical studies, the electromechanical implant produced by the FDM 3D printer was chosen as the optimal electromechanical implant in this study. Along with the designed small circuit, this implant can release a drug dosage in the patient's body at the physician's demand.
Topics: Drug Delivery Systems; Drug Liberation; Gold; Printing, Three-Dimensional; Prostheses and Implants
PubMed: 38218044
DOI: 10.1016/j.jmbbm.2023.106352 -
Zeitschrift Fur Rheumatologie May 2024Phalangeal microgeodic syndrome (PMS) is a rare osteolytic disorder of unknown etiology that typically affects children up to 15 years old during colder months....
Phalangeal microgeodic syndrome (PMS) is a rare osteolytic disorder of unknown etiology that typically affects children up to 15 years old during colder months. Transient peripheral circulatory impairment probably underlines its pathogenesis. Conservative treatment with eviction of cold exposure is often successful. We report the case of a young woman presenting with joint pain in her feet, along with toe discoloration and redness, where a diagnosis of PMS was established based on magnetic resonance imaging findings and exclusion of other differential diagnostic entities. Pharmacological treatment was deemed necessary for symptomatic relief, but a trial of calcium channel blocker (CCB) was not tolerated by the patient. The patient was then started on pentoxifylline, with significant clinical improvement.
Topics: Female; Humans; Diagnosis, Differential; Pentoxifylline; Syndrome; Treatment Outcome
PubMed: 38175270
DOI: 10.1007/s00393-023-01470-y -
Clinical Nephrology. Case Studies 2023We present two atypical cases of calciphylaxis presenting with ocular ischemic pathology - both without the hallmark cutaneous manifestations - to raise awareness of...
PURPOSE
We present two atypical cases of calciphylaxis presenting with ocular ischemic pathology - both without the hallmark cutaneous manifestations - to raise awareness of this rare yet highly disabling condition.
OBSERVATIONS
We report two cases of ophthalmic calciphylaxis presenting as (1) anterior ischemic optic neuropathy (AION) and cilioretinal artery occlusion in a 76-year-old woman with pre-dialysis kidney failure, and (2) AION with contralateral central retinal artery occlusion (CRAO) in a 44-year-old man on hemodialysis.
CONCLUSION AND IMPORTANCE
These cases highlight the need for judicious clinical suspicion of calciphylaxis in patients with kidney failure, presenting with microvascular ischemic ophthalmic pathology such as AION or CRAO. Confirmation with temporal artery biopsy is essential to direct targeted individualized multi-disciplinary treatment of calciphylaxis and avoid unnecessary steroid exposure in cases masquerading as giant cell arteritis (GCA).
PubMed: 38169875
DOI: 10.5414/CNCS111088 -
Recenti Progressi in Medicina Jan 2024Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria and progressive impairment in renal function. Pentoxifylline is a non-specific... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria and progressive impairment in renal function. Pentoxifylline is a non-specific inhibitor of phosphodiesterase with anti-inflammatory properties which may have therapeutic potency in patients with diabetic kidney disease.
OBJECTIVE
The present study is aimed at evaluating the efficacy of pentoxifylline as a treatment strategy for alleviating the microalbuminuria in type-2 diabetic patients with nephropathy.
METHODS
This double-blind randomized clinical trial was performed on outpatients with type 2 diabetic nephropathy who presented urine albumin excretion of 30-300 mg per 24 hours on at least three consecutive occasions. A total of 58 patients were randomly assigned to the treatment and control groups. The treatment group (n=29) received pentoxifylline (400 mg/day) for 3 months in addition to the standard drugs for diabetic nephropathy (Raas blockers), while the control group (n=29) received placebo as add-on therapy. Finally, urine albumin test was measured before and after 3 months of treatment and compared between the two groups.
RESULTS
Before the intervention, no significant difference in the levels of albuminuria was observed between the two groups (153.21±130.80 mg/day vs. 159.93 ±130.45; p=0.845); but after 12 weeks of treatment, albuminuria in the treatment group was significantly reduced compared to the placebo group (29.59 ±27.88 mg/day vs. 160.48±129.53 mg/day; p<0.0001). At the end of the study, the response rate to treatment (more than 50% reduction in albuminuria) was 89.7% in the pentoxifylline group, while no response to treatment was observed in the placebo group (p<0.0001).
CONCLUSIONS
Pentoxifylline as add-on therapy to the conventional treatment (Raas blockers) may reduce the microalbuminuria in patients with diabetic nephropathy without any side effects.
Topics: Humans; Albuminuria; Pentoxifylline; Diabetic Nephropathies; Diabetes Mellitus, Type 2; Albumins; Double-Blind Method
PubMed: 38169355
DOI: 10.1701/4169.41640 -
Aging Cell Mar 2024Pericytes are mesenchymal cells that surround endothelial cells, playing a crucial role in angiogenesis and vessel maturation. Additionally, they are associated with...
Pericytes are mesenchymal cells that surround endothelial cells, playing a crucial role in angiogenesis and vessel maturation. Additionally, they are associated with interstitial fibrosis as a major contributor to renal myofibroblasts. In this study, we aim to investigate whether the phosphodiesterase inhibitor, pentoxifylline (PTX), can ameliorate aging-related functional and histological deterioration in the kidney. We subjected aging C57BL/6 mice, dividing into young, aging, and PTX-treated aging groups. Renal function, albuminuria, and histological changes were assessed. Interstitial pericytes were assessed by immunohistochemistry analysis. We examined changes in pericytes in elderly patients using human kidney tissue obtained from healthy kidney donors for kidney transplantation. In vitro experiments with human pericytes and endothelial cells were performed. Aging mice exhibited declined renal function, increased albuminuria, and aging-related histological changes including mesangial expansion and tubulointerstitial fibrosis. Notably, number of pericytes declined in aging kidneys, and myofibroblasts increased. PTX treatment ameliorated albuminuria, histological alterations, and microvascular rarefaction, as well as modulated angiopoietin expression. In vitro experiments showed PTX reduced cellular senescence and inflammation. Human kidney analysis confirmed similar pericyte changes in aging kidneys. The phosphodiesterase inhibitor, PTX preserved microvascular density and improved renal interstitial fibrosis and inflammation in aging mice kidneys. These protective effects were suggested to be associated with the amelioration of pericytes reduction and the transition to myofibroblasts. Additionally, the upregulation of angiopoietin-1 expression may exert potential impacts. To the best of our knowledge, this is the first report on the changes in renal interstitial pericytes in aging human kidneys.
Topics: Humans; Mice; Animals; Aged; Pericytes; Phosphodiesterase Inhibitors; Endothelial Cells; Albuminuria; Mice, Inbred C57BL; Kidney; Kidney Diseases; Aging; Fibrosis; Inflammation
PubMed: 38155524
DOI: 10.1111/acel.14075 -
Biomedicines Dec 2023Osteoradionecrosis (ORN) is a serious long-term complication of head and neck radiotherapy (RT), which is often triggered by dental extractions. It results from... (Review)
Review
Osteoradionecrosis (ORN) is a serious long-term complication of head and neck radiotherapy (RT), which is often triggered by dental extractions. It results from avascular aseptic necrosis due to irradiated bone damage. ORN is challenging to treat and can lead to severe complications. Furthermore, ORN causes pain and distress, significantly reducing the patient's quality of life. There is currently no established preventive strategy. This narrative review aims to provide an update for the clinicians on the risk of ORN associated with oral surgery in head and neck RT patients, with a focus on the timing suitable for the oral surgery and possible ORN preventive treatments. An electronic search of articles was performed by consulting the PubMed database. Intervention and observational studies were included. A multidisciplinary approach to the patient is highly recommended to mitigate the risk of RT complications. A dental visit before commencing RT is highly advised to minimize the need for future dental extractions after irradiation, and thus the risk of ORN. Post-RT preventive strategies, in case of dento-alveolar surgery, have been proposed and include antibiotics, hyperbaric oxygen (HBO), and the combined use of pentoxifylline and tocopherol ("PENTO protocol"), but currently there is a lack of established standards of care. Some limitations in the use of HBO involve the low availability of HBO facilities, its high costs, and specific clinical contraindications; the PENTO protocol, on the other hand, although promising, lacks clinical trials to support its efficacy. Due to the enduring risk of ORN, removable prostheses are preferable to dental implants in these patients, as there is no consensus on the appropriate timing for their safe placement. Overall, established standards of care and high-quality evidence are lacking concerning both preventive strategies for ORN as well as the timing of the dental surgery. There is an urgent need to improve research for more efficacious clinical decision making.
PubMed: 38137559
DOI: 10.3390/biomedicines11123339 -
Biomolecules Dec 2023Gout is characterized by the formation of monosodium urate crystals in peripheral joints. We carried out laboratory studies to investigate the effect of adding nine...
Gout is characterized by the formation of monosodium urate crystals in peripheral joints. We carried out laboratory studies to investigate the effect of adding nine different methylxanthines and two different methylated uric acid derivatives on the development of these crystals over the course of 96 h in a medium whose composition was similar to that of synovial fluid. Our results showed that 7-methylxanthine reduced or totally prevented crystal formation; 1-methylxanthine, 3-methylxanthine, 7-methyluric acid, and 1,3-dimethyluric acid had weaker effects, and the other molecules had no apparent effect. The presented results indicate that a 7-methylxanthine concentration of about 6 × 10 M (10 mg/L) prevented the formation of crystals for an initial urate concentration of 1.78 × 10 M (300 mg/L) in the presence of 0.4 M of Na for 96 h at 25 °C and a pH of 7.4. We attribute these results to alterations in thermodynamics, not kinetics. Our results suggest that prevention of crystallization in vivo could be achieved by direct oral administration of 7-methylxanthine or other methylxanthines that are metabolized to 7-methylxanthine. For example, the hepatic metabolism of theobromine leads to significant plasma levels of 7-methylxanthine (14% of the initial theobromine concentration) and 3-methylxanthine (6% of the initial theobromine concentration); however, 7-methyluric acid is present at very low concentrations in the plasma. It is important to consider that several of the specific molecules we examined (theobromine, caffeine, theophylline, dyphylline, etophylline, and pentoxifylline) did not directly affect crystallization.
Topics: Uric Acid; Theobromine; Solubility; Caffeine
PubMed: 38136640
DOI: 10.3390/biom13121769