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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 -
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 -
Naunyn-Schmiedeberg's Archives of... Jul 2024Ischemic heart diseases such as myocardial infarction (MI) are a global health problem and a leading cause of mortality worldwide. Angiogenesis is an important approach...
Ischemic heart diseases such as myocardial infarction (MI) are a global health problem and a leading cause of mortality worldwide. Angiogenesis is an important approach for myocardial healing following ischemia. Thus, this study aimed to explore the potential cardiac angiogenic effects of selenium (Se), alone and in combination with the tumor necrosis factor-alpha inhibitor, pentoxifylline (PTXF), via Akt/HIF-1α signaling. MI was induced in rats using two subcutaneous doses of isoprenaline (ISP) at a 24-h interval (150 mg/kg). One week later, rats were orally given Se (150 µg/kg/day), PTXF (50 mg/kg/day), or Se/PTXF combination. ISP-induced myocardial damage was evident by increased HW/TL ratios, ST segment elevation, and increased serum levels of CK-MB, LDH, and troponin-I. ISP increased the cardiac levels of the lipid peroxidation marker MDA; the pro-inflammatory cytokines IL-6, IL-1β, and TNF-α; and the pro-apoptotic protein Bax and caspase-3. In contrast, the cardiac levels of the antioxidant markers GSH and SOD and the anti-apoptotic marker Bcl-2 were reduced. Furthermore, ISP markedly increased the cardiac levels of p-Akt and HIF-1α proteins and the cardiac gene expression of ANGPT-1, VEGF, and FGF-2. Treatment with Se both alone and in combination with PTXF ameliorated the ISP-induced myocardial damage and further increased cardiac angiogenesis via Akt/HIF-1α signaling. Se/PTXF combined therapy was more beneficial than individual treatments. Our study revealed for the first time the cardiac angiogenic effects of Se both alone and in combination with PTXF in myocardial infarction, suggesting that both may be promising candidates for clinical studies.
Topics: Animals; Hypoxia-Inducible Factor 1, alpha Subunit; Myocardial Infarction; Proto-Oncogene Proteins c-akt; Selenium; Male; Signal Transduction; Neovascularization, Physiologic; Disease Models, Animal; Pentoxifylline; Rats, Wistar; Rats; Myocardium; Drug Therapy, Combination; Angiogenesis Inducing Agents; Isoproterenol; Tumor Necrosis Factor-alpha; Angiogenesis
PubMed: 38112730
DOI: 10.1007/s00210-023-02904-9 -
Cureus Nov 2023Relapsing polychondritis (RP) is a rare autoimmune condition that involves the recurrent inflammation of cartilage throughout the body, with a predilection for auricular...
Relapsing polychondritis (RP) is a rare autoimmune condition that involves the recurrent inflammation of cartilage throughout the body, with a predilection for auricular and nasal cartilage. Given its rarity and diverse clinical presentations, RP is frequently misdiagnosed or left untreated, which can lead to significant morbidity and mortality. When it is correctly diagnosed, there are no standardized guidelines on the treatment of RP to date. Management of this disease requires a multidisciplinary approach, and about 30% of patients with RP have other autoimmune disorders, further complicating the approach to targeted treatment. Biologic agents (including TNF inhibitors) are commonly used. We present a compelling case of a 46-year-old female with rheumatoid arthritis (well-controlled on adalimumab) and hypothyroidism who presented to the dermatology clinic with recurrent episodes of painful, swollen, and erythematous ears, leading to a clinical diagnosis of relapsing polychondritis. Off-label use of oral pentoxifylline, along with topical corticosteroids, led to significant improvement in her symptoms. Dermatologists play an important role in the diagnosis of this rare disorder, as skin manifestations may be the initial presenting sign of RP. Further research into potentially effective treatments is needed. Timely identification and management of RP may prevent the progression of cartilage destruction, thus improving patients' long-term prognosis and overall quality of life.
PubMed: 38106732
DOI: 10.7759/cureus.48849 -
The Journal of Clinical and Aesthetic... Nov 2023Alopecia areata (AA) is a common form of potentially reversible non-scarring hair disorder characterized by limited patchy hair loss (alopecia areata), loss of all scalp...
OBJECTIVE
Alopecia areata (AA) is a common form of potentially reversible non-scarring hair disorder characterized by limited patchy hair loss (alopecia areata), loss of all scalp hair (alopecia totalis), or all body hair (alopecia universalis). Several lines of treatment have been used with variable outcomes. We aimed to compare the efficacy of intralesional pentoxifylline (PTX) and triamcinolone acetonide (TRA) injection in the treatment of alopecia areata.
METHODS
Our study included 60 patients with localized AA recruited from the Dermatology Outpatient Clinics of Al-Azhar University Hospitals. Patients were divided into two groups of alopecia areata patches; Group A who received intralesional TRA injections while Group B received intralesional PTX.
RESULTS
The study showed that both modalities are effective in treating AA and each modality has its own advantages. According to the response, patients were grouped into three categories: partial response (0-33% terminal hair regrowth), moderate response (33-66% terminal hair regrowth), and high response (66-100% terminal hair regrowth). The high response after use of the PTX was found in 50 percent of patients. The high response was observed in 46.6 percent of patients treated with TRA.
LIMITATIONS
Small sample size and short follow-up period.
CONCLUSION
This study showed that intralesional injection of PTX seems to be effective and safe treatment for localized AA and could be used as a good alternative to triamcinolone acetonide.
PubMed: 38076656
DOI: No ID Found -
Cureus Nov 2023Sperm motility is an essential selection criteria by embryologists at the time of intracytoplasmic sperm injection (ICSI). One method of testing sperm viability is to... (Review)
Review
Sperm motility is an essential selection criteria by embryologists at the time of intracytoplasmic sperm injection (ICSI). One method of testing sperm viability is to induce sperm motility by increasing cyclic adenosine monophosphate (cAMP) levels by treating a semen sample with phosphodiesterase inhibitors (PDEIs), such as theophylline and pentoxifylline. It explores the implications of PDEI in medical care, reflecting on its effects in clinical settings and recognizing potential topics for future exploration. This analysis revealed that by incorporating stimulants that activate movements, the time it took to single out sperms was markedly reduced, and consequently, the sperms were safeguarded from a prolonged period of oxidative stress. Furthermore, theophylline was found to advance sperm motility, consequently resulting in several initially immobile spermatozoa displaying rapid progressive motility. Higher fertilization rate, cleavage rate, good quality embryos (grade I), and higher biochemical and clinical pregnancy rates were found with artificial sperm activation (ASA) using pentoxifylline and theophylline. This review emphasizes the need for more research to evaluate the drug's long-term safety and investigate the effects of theophylline and pentoxifylline on postfertilization parameters, such as embryo development, implantation, and pregnancy outcomes. These areas of investigation are important for understanding the complete impact of these agents and to ensure their safe and effective implementation in clinical practice.
PubMed: 38054131
DOI: 10.7759/cureus.48192 -
Pediatric Investigation Dec 2023
PubMed: 38050532
DOI: 10.1002/ped4.12393 -
Drug Design, Development and Therapy 2023To develop an UPLC-MS/MS method for the quantitative analysis of pentoxifylline in beagle dog plasma and apply it to a pharmacokinetic study of food effect.
PURPOSE
To develop an UPLC-MS/MS method for the quantitative analysis of pentoxifylline in beagle dog plasma and apply it to a pharmacokinetic study of food effect.
METHODS
Sample separation was achieved using a Kinetex Phenyl-Hexyl column (50 × 2.1 mm, 1.7 μm) with a gradient elution program in 5.5 min after a simple protein precipitation with methanol. Using the mobile phase that made up by 0.2% formic acid and 5mM ammonium formate water (A) and methanol (B). Quantitation was carried out using the positive ionization mode with multiple reaction monitoring (MRM). A randomized, single-dose, two-period crossover study was conducted in six fasted or fed beagles that received 400 mg pentoxifylline sustained-release tablets (Brand name: Shuanling™, CSPC Pharmaceutical Group). WinNonlin software was used to calculate pharmacokinetic parameters.
RESULTS
The linear calibration range was 2-1000 ng/mL (r> 0.99). Both intra- and inter-batch precision were less than 6.27%, and the accuracy ranged from 88.65% to 97.18%. Pentoxifylline was readily absorbed in fasted and fed dogs administered a dose of 400 mg (t:1.54h vs 1.83h). Compared to the fasted group, the AUC and C in the fed group increased by 1.71-fold and 1.30-fold, respectively. In the fasted group, the AUC and C values were 4684.08 h•ng/mL and 2402.33 ng/mL, respectively. In the fed group, these values were 8027.75 h•ng/mL and 3119.67 ng/mL. The difference in AUC between the fed and fasted group was statistically significant.
CONCLUSION
The novel optimized UPLC-MS/MS assay is an effective tool for the determination of pentoxifylline and has been successfully applied in pharmacokinetic studies of pentoxifylline in beagle dogs. The administration of pentoxifylline sustained-release tablets with food significantly increased the area under the time curve, and it is recommended that they should be administered during or shortly after feeding.
Topics: Animals; Dogs; Chromatography, High Pressure Liquid; Chromatography, Liquid; Cross-Over Studies; Delayed-Action Preparations; Methanol; Pentoxifylline; Reproducibility of Results; Tandem Mass Spectrometry
PubMed: 38046282
DOI: 10.2147/DDDT.S434492