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Naunyn-Schmiedeberg's Archives of... May 2024This meta-analysis aimed to comprehensively evaluate the efficacy and safety of pentoxifylline (PTF) in the treatment of diabetic nephropathy (DN) and to offer fresh... (Meta-Analysis)
Meta-Analysis
This meta-analysis aimed to comprehensively evaluate the efficacy and safety of pentoxifylline (PTF) in the treatment of diabetic nephropathy (DN) and to offer fresh perspectives and evidence-based references for this condition. Meta-analysis. Relevant randomized controlled trials (RCTs) were searched from PubMed, Embase, Cochrane Library, China Knowledge Network (CNKI), Wanfang, and China Biomedical Literature Database. All trials were screened for compliance with the inclusion and exclusion criteria, and relevant data were extracted after quality evaluation. Eighteen studies with a total of 1280 patients were finally included. Compared to the control group, high sensitivity C-reactive protein (hsCRP) was improved (MD = - 0.23. 95% CI = [- 0.41, - 0.05], P = 0.01); urinary albumin excretion (UAE) rate was reduced (MD = - 16.50, 95% CI = [- 18.87, - 14.13], P<0.00001); the change of serum creatinine (Scr) from baseline was reduced (MD = - 0.05, 95%CI = [- 0.08, - 0.01], P = 0.009); fasting plasma glucose (FPG) was decreased (MD = - 5.66, 95% CI = [- 9.79, - 1.53], P = 0.007); and the improvement of glomerular filtration rate (eGFR) from baseline was increased (MD = 4.38, 95% CI = [3.28, 5.48], P<0.00001) in the treatment group. No significant difference was observed between the two groups concerning systolic blood pressure, diastolic blood pressure, total cholesterol, and triglycerides. And in terms of safety, the use of PTF was relatively safe with some self-limiting adverse events. FPG was decreased by PTF more effectively, but there was no effect of PTF on glycated hemoglobin (HbA1c). PTF could improve hsCRP, decrease UAE and Scr, and raise eGFR in the treatment of DN.
Topics: Humans; Blood Glucose; C-Reactive Protein; Creatinine; Diabetic Nephropathies; Pentoxifylline; Randomized Controlled Trials as Topic; Vasodilator Agents
PubMed: 37987795
DOI: 10.1007/s00210-023-02842-6 -
Journal of Applied Physiology... Jan 2024Previous studies have suggested that the loss of microvessel density in the peripheral circulation with evolving metabolic disease severity represents a significant...
Previous studies have suggested that the loss of microvessel density in the peripheral circulation with evolving metabolic disease severity represents a significant contributor to impaired skeletal muscle oxygenation and fatigue-resistance. Based on this and our recent work, we hypothesized that cerebral microvascular rarefaction was initiated from the increased prooxidant and proinflammatory environment with metabolic disease and is predictive of the severity of the emergence of depressive symptoms in obese Zucker rats (OZRs). In male OZR, cerebrovascular rarefaction followed the emergence of elevated oxidant and inflammatory environments characterized by increased vascular production of thromboxane A (TxA). The subsequent emergence of depressive symptoms in OZR was associated with the timing and severity of the rarefaction. Chronic intervention with antioxidant (TEMPOL) or anti-inflammation (pentoxifylline) therapy blunted the severity of rarefaction and depressive symptoms, although the effectiveness was limited. Blockade of TxA production (dazmegrel) or action (SQ-29548) resulted in a stronger therapeutic effect, suggesting that vascular production and action represent a significant contributor to rarefaction and the emergence of depressive symptoms with chronic metabolic disease (although other pathways clearly contribute as well). A de novo biosimulation of cerebrovascular oxygenation in the face of progressive rarefaction demonstrates the increased probability of generating hypoxic regions within the microvascular networks, which could contribute to impaired neuronal metabolism and the emergence of depressive symptoms. The results of the present study also implicate the potential importance of aggressive prodromic intervention in reducing the severity of chronic complications arising from metabolic disease. With clinical studies linking vascular disease risk to depressive symptom emergence, we used obese Zucker rats, a model of chronic metabolic disease, to identify potential mechanistic links between these two negative outcomes. Depressive symptom severity correlated with the extent of cerebrovascular rarefaction, after increased vascular oxidant stress/inflammation and TxA production. Anti-TxA interventions prevasculopathy blunted rarefaction and depressive symptoms, while biosimulation indicated that cerebrovascular rarefaction increased hypoxia within capillary networks as a potential contributing mechanism.
Topics: Animals; Rats; Male; Metabolic Syndrome; Thromboxanes; Depression; Rats, Zucker; Microvascular Rarefaction; Obesity; Metabolic Diseases; Oxidants
PubMed: 37969083
DOI: 10.1152/japplphysiol.00410.2023 -
Investigative Ophthalmology & Visual... Nov 2023The purpose of this study was to determine the role of nuclear factor kappa B (NF-κB) c-Rel during acute corneal transplant rejection and whether targeting c-Rel can...
PURPOSE
The purpose of this study was to determine the role of nuclear factor kappa B (NF-κB) c-Rel during acute corneal transplant rejection and whether targeting c-Rel can reduce corneal transplant rejection.
METHODS
Allogeneic corneal transplantation was performed in wild-type and c-Rel-deficient mice. Corneal graft survival rate, opacity, neovascularization, and edema were evaluated by slit-lamp microscopy. Adeno-associated virus 6 (AAV6) expressing c-Rel-specific small hairpin RNA (AAV6-shRel) and the small-molecule compound pentoxifylline (PTXF) were used to reduce c-Rel expression. Enzyme-linked immunosorbent assay was used to determine the expression of inflammatory cytokines. c-Rel expression was determined by quantitative RT-PCR and western blot. The effect of c-Rel inhibition on corneal transplant rejection was examined using a mouse model of acute allogeneic corneal transplantation. Tear production and corneal sensitivity were measured to determine the potential toxicity of AAV6-shRel and PTXF.
RESULTS
The expression of c-Rel and its inflammatory targets was increased in both mice and patients with corneal transplant rejection. Loss of c-Rel reduced corneal transplant rejection in mouse. Both AAV6-shRel and PTXF were able to downregulate the expression of c-Rel and its inflammatory targets in vitro. Treatment with AAV6-shRel or PTXF reduced corneal transplant rejection in mouse and downregulated the expression of inflammatory cytokines in peripheral blood mononuclear cells from patients with corneal transplant rejection. Treatment with AAV6-shRel or PTXF displayed no side effects on tear production or corneal sensitivity.
CONCLUSIONS
Increased expression of c-Rel is a risk factor for acute corneal transplant rejection, and targeting c-Rel can efficiently reduce corneal transplant rejection.
Topics: Humans; Animals; Mice; NF-kappa B; Leukocytes, Mononuclear; Cornea; Corneal Transplantation; Cytokines
PubMed: 37962530
DOI: 10.1167/iovs.64.14.16 -
Pharmaceuticals (Basel, Switzerland) Oct 2023The involvement of NK and other cytotoxic cells is considered the first defense line against cancer. However, a significant lack of information prevails on the possible...
The involvement of NK and other cytotoxic cells is considered the first defense line against cancer. However, a significant lack of information prevails on the possible roles played by factors considered characteristic of primitive cells, such as c-kit and Sca-1, in activating these cells, particularly in melanoma models subjected to treatments with substances under investigation, such as the case of norcantharidin. In this study, B16F1 murine melanoma cells were used to induce tumors in DBA/2 mice, estimating the proportions of NK and iNKT cells; the presence of activation (CD107a+) and primitive/activation (c-kit+/Lya6A+) markers and some tumor parameters, such as the presence of mitotic bodies, nuclear factor area, NK and iNKT cell infiltration in the tumor, infiltrated tumor area, and infiltrating lymphocyte count at 10x and 40x in specimens treated with pentoxifylline, norcantharidin, and the combination of both drugs. Possible correlations were estimated with Pearson's correlation analysis. It should be noted that, despite having demonstrated multiple correlations, immaturity/activation markers were related to these cells' activation. At the tumor site, iNKT cells are the ones that exert the cytotoxic potential on tumor cells, but they are confined to specific sites in the tumor. Due to the higher number of interactions of natural killer cells with tumor cells, it is concluded that the most effective treatment was PTX at 60 mg/kg + NCTD at 0.75 mg/kg.
PubMed: 37895943
DOI: 10.3390/ph16101472 -
Biomedicines Oct 2023Chronic kidney disease (CKD) is a progressive and incurable disease that impairs kidney function. Its prevalence is estimated to affect up to 800 million individuals... (Review)
Review
Chronic kidney disease (CKD) is a progressive and incurable disease that impairs kidney function. Its prevalence is estimated to affect up to 800 million individuals within the general population, and patients with diabetes and hypertension are particularly at risk. This disorder disrupts the physiological mechanisms of the body, including water and electrolyte balance, blood pressure regulation, the excretion of toxins, and vitamin D metabolism. Consequently, patients are exposed to risks such as hyperkalemia, hyperphosphatemia, metabolic acidosis, and blood pressure abnormalities. These risks can be reduced by implementing appropriate diagnostic methods, followed by non-pharmacological (such as physical activity, dietary, and lifestyle adjustment) and pharmacological strategies after diagnosis. Selecting the appropriate diet and suitable pharmacological treatment is imperative in maintaining kidney function as long as possible. Drugs such as finerenone, canakinumab, and pentoxifylline hold promise for improved outcomes among CKD patients. When these interventions prove insufficient, renal replacement therapy becomes essential. This is particularly critical in preserving residual renal function while awaiting renal transplantation or for patients deemed ineligible for such a procedure. The aim of this study is to present the current state of knowledge and recent advances, providing novel insights into the treatment of chronic kidney disease.
PubMed: 37893119
DOI: 10.3390/biomedicines11102746 -
Advances in Respiratory Medicine Oct 2023Cardiogenic pulmonary edema (CPE) is characterized by the development of acute respiratory failure associated with the accumulation of fluid in the lung's alveolar... (Review)
Review
Cardiogenic pulmonary edema (CPE) is characterized by the development of acute respiratory failure associated with the accumulation of fluid in the lung's alveolar spaces due to an elevated cardiac filling pressure. All cardiac diseases, characterized by an increasing pressure in the left side of the heart, can cause CPE. High capillary pressure for an extended period can also cause barrier disruption, which implies increased permeability and fluid transfer into the alveoli, leading to edema and atelectasis. The breakdown of the alveolar-epithelial barrier is a consequence of multiple factors that include dysregulated inflammation, intense leukocyte infiltration, activation of procoagulant processes, cell death, and mechanical stretch. Reactive oxygen and nitrogen species (RONS) can modify or damage ion channels, such as epithelial sodium channels, which alters fluid balance. Some studies claim that these patients may have higher levels of surfactant protein B in the bloodstream. The correct approach to patients with CPE should include a detailed medical history and a physical examination to evaluate signs and symptoms of CPE as well as potential causes. Second-level diagnostic tests, such as pulmonary ultrasound, natriuretic peptide level, chest radiograph, and echocardiogram, should occur in the meantime. The identification of the specific CPE phenotype is essential to set the most appropriate therapy for these patients. Non-invasive ventilation (NIV) should be considered early in the treatment of this disease. Diuretics and vasodilators are used for pulmonary congestion. Hypoperfusion requires treatment with inotropes and occasionally vasopressors. Patients with persistent symptoms and diuretic resistance might benefit from additional approaches (i.e., beta-agonists and pentoxifylline). This paper reviews the pathophysiology, clinical presentation, and management of CPE.
Topics: Humans; Pulmonary Edema; Lung; Heart Failure; Oxygen; Vasodilator Agents; Emergency Medicine
PubMed: 37887077
DOI: 10.3390/arm91050034 -
Journal of Vascular and Interventional... Feb 2024Guidelines based on randomized controlled data recommend patients with newly diagnosed venous leg ulcers (VLUs) to undergo venous reflux duplex ultrasound (US) and be...
Guidelines based on randomized controlled data recommend patients with newly diagnosed venous leg ulcers (VLUs) to undergo venous reflux duplex ultrasound (US) and be considered for treatment with pentoxifylline to accelerate ulcer healing. A retrospective review was conducted of 2,061 patients with VLU diagnosed between 2011 and 2020 in a rural health care system to identify factors associated with increased or decreased likelihood of being prescribed venous reflux duplex US and pentoxifylline. Venous reflux duplex US (16%) and pentoxifylline (0.7%) were prescribed infrequently. Evaluation by a vascular specialist was associated with a significantly increased frequency of undergoing venous reflux duplex US (5%-38%). Seeing a wound care specialist was associated with an increased frequency of being prescribed pentoxifylline (0.7%-1.4%). Increased referral to specialists and/or referring clinician education on guideline-based care may be of benefit to patients with VLUs. Pentoxifylline seems underused, even by specialists. Further study is needed to confirm these findings and determine whether they are generalizable.
Topics: Humans; Varicose Ulcer; Pentoxifylline; Ultrasonography; Ultrasonography, Doppler, Duplex; Delivery of Health Care; Leg Ulcer
PubMed: 37865229
DOI: 10.1016/j.jvir.2023.10.007 -
Ophthalmic Surgery, Lasers & Imaging... Nov 2023Many interventions for nonarteritic central retinal artery occlusion (CRAO) are associated with serious complications and little effect on visual outcomes. We report on... (Review)
Review
Many interventions for nonarteritic central retinal artery occlusion (CRAO) are associated with serious complications and little effect on visual outcomes. We report on the findings of a Cochrane systematic review that searched seven databases for peer-reviewed articles reporting on treatments for acute nonarteritic CRAO. We assessed six randomized controlled trials, including interventions such as tissue plasminogen activator (t-PA), isovolumic hemodilution, eyeball massage, intraocular pressure reduction, anticoagulation, vasodilation, oxygen inhalation, laser embolysis, transcorneal electrical stimulation, thrombolysis, pentoxifylline, and enhanced external counterpulsation. However, none of the randomized controlled trials demonstrated significant improvement in visual acuity at 1 month compared to observation, and some patients treated with t-PA experienced serious adverse effects including intracranial hemorrhage. Proposed interventions for acute nonarteritic CRAO may not be better than observation, but the evidence is uncertain. Larger, well-designed studies are necessary to determine the most effective management option for acute nonarteritic CRAO. .
Topics: Humans; Tissue Plasminogen Activator; Retinal Artery Occlusion; Thrombolytic Therapy; Hemodilution; Eye
PubMed: 37855834
DOI: 10.3928/23258160-20230922-01 -
Annals of Dermatology May 2023Livedoid vasculopathy (LV) is a chronic coagulation disorder characterized by recurrent, painful ulcers on the lower extremities. Methylene tetrahydrofolate reductase ()...
Livedoid vasculopathy (LV) is a chronic coagulation disorder characterized by recurrent, painful ulcers on the lower extremities. Methylene tetrahydrofolate reductase () gene polymorphism is associated with coagulopathy. Therapeutic options usually include anti-inflammatory or immunosuppressive agents. However, the condition is still highly challenging to manage and no consensus over the first-line treatment for LV exists. Furthermore, when LV is accompanied with gene polymorphism, clinical presentations could be more severe and resistant to treatment. We report a case of refractory LV accompanied by gene polymorphism, which was successfully treated with hyperbaric oxygen therapy (HBOT). A 63-year-old female patient presented with multiple painful ulcers, atrophie blanches, and retiform purpura on both lower legs and feet. Histopathologic findings were compatible with LV. LV was diagnosed based on these clinicopathological findings. Following the diagnosis, we treated the patient with pentoxifylline, aspirin, systemic corticosteroid, antihistamine, and antibiotics. In spite of six-month treatment, the skin lesions did not improve; hence, HBOT was performed. It was performed at 2.0 absolute atmosphere for 120 minutes each time, three times a week. After 4 sessions, the ulcers began to heal and after 13 sessions, the skin lesions almost healed. During the eight-month follow-up period, the skin ulcers did not recur and the symptoms remained stable. Additionally, it was confirmed that she had gene polymorphism after a genetic test. In conclusion, we wish to provide evidence regarding the effectiveness of HBOT and suggest that HBOT might be a considerable treatment option in refractory LV.
PubMed: 37853867
DOI: 10.5021/ad.20.330 -
A Systematic Review and Bayesian Network Meta-Analysis of Medical Therapies for Lichen Planopilaris.Dermatology (Basel, Switzerland) 2024Lichen planopilaris (LPP) is a primary chronic lymphocytic cutaneous disorder that selectively destroys the hair follicles, resulting in scarring alopecia.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lichen planopilaris (LPP) is a primary chronic lymphocytic cutaneous disorder that selectively destroys the hair follicles, resulting in scarring alopecia. Unfortunately, current available treatments are not fully effective to stop hair loss, and the level of evidence for medical interventions is weak.
OBJECTIVES
The present article aimed to determine the efficacy of the different medical interventions in LPP through a network meta-analysis (NMA).
METHODS
A systematic review and meta-analysis were performed including randomized trials that report the outcomes of lichen planopilaris activity index (LPPAI). These articles were pooled and a NMA was conducted.
RESULTS
A total of seven studies were identified and included in meta-analysis, comprising 251 LPP patients. The NMA showed the mean difference in LLPAI was significantly superior with the combination of clobetasol plus N-acetylcysteine (mean difference: -2.0, 95% CI = -3.43 to -0.51) and the combination of clobetasol plus pentoxifylline (mean difference: -1.62, 95% CI = -3.0 to -0.25) compared to the treatment of reference (clobetasol). The NMA showed cyclosporine (mean difference: 2.05 95% CI = 0.68-3.49), methotrexate (mean difference: 1.95 95% CI = 1.23-3.17), the combination of methotrexate plus prednisolone (mean difference: 1.56 95% CI = 0.25-2.96) were significantly worse than hydroxychloroquine according to the differences in LLPAI.
CONCLUSION
This work is the first NMA in LPP and hence, it can be helpful in serving as an initial step toward better evidence-based decisions in the treatment of this challenging condition. We propose a triple-combined approach consisting of topical clobetasol, hydroxychloroquine, and N-acetylcysteine as resulted in the most effective approach. Considering the poor outcomes observed with pioglitazone, mycophenolate mofetil, and cyclosporine, it is advisable to contemplate the use of these medications in patients who have not responded adequately to more efficacious alternatives.
Topics: Humans; Clobetasol; Methotrexate; Network Meta-Analysis; Acetylcysteine; Bayes Theorem; Hydroxychloroquine; Lichen Planus; Cyclosporine; Alopecia; Chronic Disease
PubMed: 37852211
DOI: 10.1159/000534364