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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 -
Calcified Tissue International Mar 2024Vascular dysfunction contributes to the development of osteopenia in hypertensive patients, as decreased blood supply to bones results in tissue damage and dysfunction....
Vascular dysfunction contributes to the development of osteopenia in hypertensive patients, as decreased blood supply to bones results in tissue damage and dysfunction. The effect of anti-hypertensive medicines on bone mass in hypertensive individuals is inconclusive because of the varied mechanism of their action, and suggests that reducing blood pressure (BP) alone is insufficient to enhance bone mass in hypertension. Pentoxifylline (PTX), a hemorheological drug, improves blood flow by reducing blood viscosity and angiogenesis, also has an osteogenic effect. We hypothesized that improving vascular function is critical to increasing bone mass in hypertension. To test this, we screened various anti-hypertensive drugs for their in vitro osteogenic effect, from which timolol and hydralazine were selected. In adult female spontaneously hypertensive rats (SHRs), timolol and hydralazine did not improve vascular function and bone mass, but PTX improved both. In female SHR animals, PTX restored bone mass, strength and mineralization, up to the level of normotensive control rats. In addition, we observed lower blood vasculature in the femur of adult SHR animals, and PTX restored them. PTX also restored the bone vascular and angiogenesis parameters that had been impaired in OVX SHR compared to sham SHR. This study demonstrates the importance of vascular function in addition to increased bone mass for improving bone health as achieved by PTX without affecting BP, and suggests a promising treatment option for osteoporosis in hypertensive patients, particularly at-risk postmenopausal women.
Topics: Humans; Rats; Female; Animals; Antihypertensive Agents; Bone Density; Timolol; Hypertension; Rats, Inbred SHR; Pentoxifylline; Hydralazine; Blood Pressure
PubMed: 38102510
DOI: 10.1007/s00223-023-01170-4 -
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 -
Cureus Oct 2023Oral submucous fibrosis (OSMF) is a precancerous disorder of the submucosa that causes inflammation and progressive fibrosis, leading to pronounced stiffness and... (Review)
Review
Oral submucous fibrosis (OSMF) is a precancerous disorder of the submucosa that causes inflammation and progressive fibrosis, leading to pronounced stiffness and trismus. Chewing betel nuts is a significant risk factor for OSMF in India. Arecoline from betel nuts and copper, which causes fibroblast dysfunction and the development of fibrotic bands, are the main components of betel quid. OSMF is distinguished by fibrosis in the submucosal region, which affects the majority of the oral cavity and results in advanced lockjaw due to rigidity in the lips, pharynx, cheeks, and upper third of the oesophageal canal, which progresses to dysphagia. The prevalence of OSMF is rising, particularly among younger generations, as more commercially available areca nut products like gutka (chewing tobacco) and others are being introduced. The severity of OSMF develops as the practice continues and is permanent. It also persists even after chewing has been stopped. The hallmark of oral submucous fibrosis (OSF) is abnormal collagen deposition. It is a precancerous condition and progresses to malignant tumours. Symptoms include ulcers, xerostomia, submucous fibrosis, burning sensation, and a reduction in mouth opening. Each of these drastically reduces the patient's quality of life. In the past, many treatment modalities have been tried but none of them has resulted in a cure for the disease. The primary focus of the treatment is to reduce the signs and symptoms so that the patient can have a better quality of life. Along with principles, conservative, medical, and surgical management issues have also been covered.
PubMed: 38022118
DOI: 10.7759/cureus.47259 -
The American Journal of Drug and... Mar 2024Optimal treatments for severe alcoholic hepatitis (SAH) remain controversial. Previous network meta-analysis showed that corticosteroid (CS) combined with... (Meta-Analysis)
Meta-Analysis
Optimal treatments for severe alcoholic hepatitis (SAH) remain controversial. Previous network meta-analysis showed that corticosteroid (CS) combined with N-acetylcysteine (NAC) was superior in reducing short-term mortality of patients with SAH. Recently, granulocyte colony-stimulating factor (G-CSF) treatments for SAH yielded promising results. To determine how currently available treatments affect the survival and complications of patients with SAH. The study was conducted following the guidelines of PRISMA. The data from PubMed, Embase, MEDLINE, Cochrane Library, and clinicaltrials.gov to October 2022 were searched, and patients with SAH with pharmacotherapy were included in our study. The primary outcome was short-term survival, and the other outcomes were medium- (3/6 months) or long-term (12 months) survival and complications after treatment. R software was used to establish network meta-analysis models and the result was expressed by the odd ratio (OR) value and 95% credible interval (Crls). A total of 31 randomized controlled trials, including 19 treatment regimens, were enrolled in our study. As the primary outcome, G-CSF+ pentoxifylline (PTX) ranked first in one-month survival and showed significant superiority when compared with the placebo (OR 8.60, 95% Crls 1.92-45.10) and CS (OR 4.95, 95% Crls 1.11-25.53). Also, G-CSF+PTX ranked first in improving three-month survival and reducing the occurrence of infection. PTX+MTD ranked first in six-month survival, and G-CSF ranked first in twelve-month survival. CS+MTD ranked first in the occurrence of gastrointestinal bleeding and hepatorenal syndrome. The combination of G-CSF and PTX showed a significant benefit in improving the short-term survival of SAH patients.
Topics: Pentoxifylline; Humans; Hepatitis, Alcoholic; Granulocyte Colony-Stimulating Factor; Network Meta-Analysis; Drug Therapy, Combination; Randomized Controlled Trials as Topic
PubMed: 38011683
DOI: 10.1080/00952990.2023.2266117 -
Hepatology Communications Dec 2023Severe alcoholic hepatitis (AH) has a high short-term mortality rate. The MELD assesses disease severity and mortality; however, it is not specific for AH. We screened...
BACKGROUND
Severe alcoholic hepatitis (AH) has a high short-term mortality rate. The MELD assesses disease severity and mortality; however, it is not specific for AH. We screened plasma samples from patients with severe AH for biomarkers of multiple pathological processes and identified predictors of short-term mortality.
METHODS
Plasma was collected at baseline from 85 patients with severe AH (MELD≥20, Maddrey's discriminant function≥32) enrolled in the Defeat Alcoholic Steatohepatitis clinical trial (investigating IL-1 receptor antagonist+pentoxifylline+zinc vs. methylprednisolone+placebo). Samples were analyzed for 43 biomarkers and the markers' association with 28- and 90-day mortalities was assessed.
RESULTS
Thirty-one (36.5%) patients died during the 90-day follow-up with similar ratios in the treatment groups. Eight biomarkers showed an association with mortality. IL-6, IL-22, interferon-α2, soluble TNF receptor 1, lipocalin-2, and α-fetoprotein levels were associated with 28-day mortality, while IL-6, IL-13, and endotoxin levels with 90-day mortality. In multivariable Cox regression, encephalopathy, lipocalin-2, and α-fetoprotein levels were independent predictors of 28-day mortality, and IL-6, IL-13, international normalized ratio levels, and age were independent predictors of 90-day mortality. The combination of IL-13 and age had superior performance in predicting 90-day mortality compared with MELD in the total cohort and the individual treatment groups.
CONCLUSIONS
We identified predictors of short-term mortality in a cohort exclusively involving patients with severe AH. We created a composite score of IL-13 and age that predicts 90-day mortality regardless of the treatment type with a performance superior to MELD in severe AH.
Topics: Humans; alpha-Fetoproteins; Biomarkers; Hepatitis, Alcoholic; Interleukin-13; Interleukin-6; Lipocalin-2; Age Factors
PubMed: 37994498
DOI: 10.1097/HC9.0000000000000296