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International Journal of Molecular... Mar 2024Diabetic kidney disease (DKD) is a major cause of chronic kidney disease (CKD), and it heightens the risk of cardiovascular incidents. The pathogenesis of DKD is thought... (Review)
Review
Diabetic kidney disease (DKD) is a major cause of chronic kidney disease (CKD), and it heightens the risk of cardiovascular incidents. The pathogenesis of DKD is thought to involve hemodynamic, inflammatory, and metabolic factors that converge on the fibrotic pathway. Genetic predisposition and unhealthy lifestyle practices both play a significant role in the development and progression of DKD. In spite of the recent emergence of angiotensin receptors blockers (ARBs)/angiotensin converting enzyme inhibitor (ACEI), sodium-glucose cotransporter 2 (SGLT2) inhibitors, and nonsteroidal mineralocorticoid receptors antagonists (NS-MRAs), current therapies still fail to effectively arrest the progression of DKD. Glucagon-like peptide 1 receptor agonists (GLP-1RAs), a promising class of agents, possess the potential to act as renal protectors, effectively slowing the progression of DKD. Other agents, including pentoxifylline (PTF), selonsertib, and baricitinib hold great promise as potential therapies for DKD due to their anti-inflammatory and antifibrotic properties. Multidisciplinary treatment, encompassing lifestyle modifications and drug therapy, can effectively decelerate the progression of DKD. Based on the treatment of heart failure, it is recommended to use multiple drugs in combination rather than a single-use drug for the treatment of DKD. Unearthing the mechanisms underlying DKD is urgent to optimize the management of DKD. Inflammatory and fibrotic factors (including IL-1, MCP-1, MMP-9, CTGF, TNF-a and TGF-β1), along with lncRNAs, not only serve as diagnostic biomarkers, but also hold promise as therapeutic targets. In this review, we delve into the potential mechanisms and the current therapies of DKD. We also explore the additional value of combing these therapies to develop novel treatment strategies. Drawing from the current understanding of DKD pathogenesis, we propose HIF inhibitors, AGE inhibitors, and epigenetic modifications as promising therapeutic targets for the future.
Topics: Humans; Diabetic Nephropathies; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Kidney; Renal Insufficiency, Chronic; Diabetes Mellitus, Type 2
PubMed: 38542060
DOI: 10.3390/ijms25063086 -
Scientific Reports Mar 2024Radiation-induced renal fibrosis (RIRF) is a progressive, irreversible condition causing chronic kidney disease. Pentoxifylline (PTX) and vitamin E may mitigate...
Radiation-induced renal fibrosis (RIRF) is a progressive, irreversible condition causing chronic kidney disease. Pentoxifylline (PTX) and vitamin E may mitigate radiation-induced damage and fibrosis. This study assesses their effectiveness. We used four groups, each with six rats: radiation therapy alone (RT-only), radiation therapy plus drug treatment (RT + drug), drug treatment alone (drug-only), and a control group. Rats were monitored for three months, with weight measurements every four weeks. Afterward, rats were analyzed biochemically and histologically, with blood and tissue samples taken for statistical comparison. No significant differences in serum creatinine levels and body weight were observed. RT-only group had more severe kidney tubule effects. Histomorphological, immunohistochemical, and TUNEL analyses showed significant RIRF mitigation in the RT + drug group. Our study highlighted molecular pathways (SMAD, TGF-beta, VEGF) and histological markers (collagens, a-SMA, fibronectin, metalloproteinases) associated with RIRF. PTX and vitamin E reduced ionizing radiation's impact on renal cells and mitigated radiation-induced kidney fibrosis. Further human studies are needed to confirm these findings.
Topics: Rats; Humans; Animals; Pentoxifylline; Vitamin E; Antioxidants; Kidney; Fibrosis
PubMed: 38521858
DOI: 10.1038/s41598-024-57850-0 -
Diabetes, Obesity & Metabolism Jun 2024Aggressive therapy of diabetic kidney disease (DKD) can not only slow the progression of DKD to renal failure but, if utilized at an early enough stage of DKD, can also... (Review)
Review
Aggressive therapy of diabetic kidney disease (DKD) can not only slow the progression of DKD to renal failure but, if utilized at an early enough stage of DKD, can also stabilize and/or reverse the decline in renal function. The currently recognized standard of therapy for DKD is blockade of the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). However, unless utilized at a very early stage, monotherapy with these drugs in DKD will only prevent or slow the progression of DKD and will neither stabilize nor reverse the progression of DKD to renal decompensation. Recently, the addition of a sodium-glucose cotransporter-2 inhibitor and/or a mineralocorticoid receptor blocker to ACE inhibitors or ARBs has been clearly shown to further decelerate the decline in renal function. The use of glucagon-like peptide-1 (GLP-1) agonists shown promise in decelerating the progression of DKD. Other drugs that may aid in the deceleration the progression of DKD are dipeptidyl peptidase-4 inhibitors, pentoxifylline, statins, and vasodilating beta blockers. Therefore, aggressive therapy with combinations of these drugs (stacking) should improve the preservation of renal function in DKD.
Topics: Humans; Diabetic Nephropathies; Angiotensin-Converting Enzyme Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Drug Therapy, Combination; Mineralocorticoid Receptor Antagonists; Disease Progression; Renin-Angiotensin System; Treatment Outcome; Angiotensin Receptor Antagonists; Glucagon-Like Peptide 1; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors
PubMed: 38516874
DOI: 10.1111/dom.15559 -
CNS Neuroscience & Therapeutics Mar 2024Retraction: Abdallah MS, Mosalam EM, Hassan A, et al. Pentoxifylline as an adjunctive in treatment of negative symptoms in chronic schizophrenia: A double-blind,...
Retraction: Abdallah MS, Mosalam EM, Hassan A, et al. Pentoxifylline as an adjunctive in treatment of negative symptoms in chronic schizophrenia: A double-blind, randomized, placebo-controlled trial. CNS Neurosci. Ther. 2023;29:354-364 (https://doi.org/10.1111/cns.14010).
Retraction: Abdallah MS, Mosalam EM, Hassan A, et al. Pentoxifylline as an adjunctive in treatment of negative symptoms in chronic schizophrenia: A double-blind, randomized, placebo-controlled trial. CNS Neurosci. Ther. 2023;29:354-364 (https://doi.org/10.1111/cns.14010) The above article, published online on November 07, 2022 in Wiley Online Library (wileyonlinelibrary.com) has been retracted by agreement between the journal's Editor-in-Chief, Xiaoming Hu, and John Wiley and Sons Ltd. Following publication, the Editor-in-Chief raised concerns about the integrity of the clinical trial. An investigation revealed significant issues regarding the reliability of the reported data. As a result, the Editor-in-Chief no longer has confidence in the validity of the results presented in this article.
PubMed: 38465469
DOI: 10.1111/cns.14668 -
CNS Neuroscience & Therapeutics Mar 2024Retraction: Abdallah MS, Ramadan AN, Omara-Reda H, et al. Double-blind, randomized, placebo-controlled pilot study of the phosphodiesterase-3 inhibitor cilostazol as an...
Retraction: Abdallah MS, Mosalam EM, Hassan A, et al. Pentoxifylline as an adjunctive in treatment of negative symptoms in chronic schizophrenia: A double-blind, randomized, placebo-controlled trial. CNS Neurosci. Ther. 2023;29:354-364 (https://doi.org/10.1111/cns.14010).
Retraction: Abdallah MS, Ramadan AN, Omara-Reda H, et al. Double-blind, randomized, placebo-controlled pilot study of the phosphodiesterase-3 inhibitor cilostazol as an adjunctive to antidepressants in patients with major depressive disorder. CNS Neurosci. Ther. 2021;27:1540-1548 (https://doi.org/10.1111/cns.13731) The above article, published online on September 21, 2021 in Wiley Online Library (wileyonlinelibrary.com) has been retracted by agreement between the journal's Editor-in-Chief, Xiaoming Hu, and John Wiley and Sons Ltd. Following publication, multiple concerns were raised by a third party about the integrity of the clinical trial. An investigation revealed significant issues regarding the reliability of the reported data. As a result, the Editor-in-Chief no longer has confidence in the validity of the results presented in this article.
PubMed: 38465461
DOI: 10.1111/cns.14667 -
Medication-related osteonecrosis of the jaw: evolving research for multimodality medical management.Supportive Care in Cancer : Official... Mar 2024Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating side effect of antiresorptive and antiangiogenic agents that can lead to progressive bone... (Review)
Review
PURPOSE
Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating side effect of antiresorptive and antiangiogenic agents that can lead to progressive bone destruction in the maxillofacial region. Dental surgery, including tooth extractions, commonly trigger the onset of MRONJ. While guidelines suggest avoiding extraction when possible, complete avoidance is not always feasible, as necrosis can develop from dental and periodontal disease without dental procedures. The goal of this article is to provide an update review of current preventive and therapeutic approaches for MRONJ.
METHODS
A comprehensive electronic search was conducted on PubMed/MEDLINE, Embase, and Scopus databases. All English articles encompassing randomized controlled trials, systematic reviews, observational studies, and case studies were reviewed. The current medical treatments and adjuvant therapies for managing MRONJ patients were critically assessed and summarized.
RESULTS
Pentoxifylline and alpha tocopherol (PENT-E), teriparatide, photobiomodulation (PBM), photodynamic therapy (PDT), and the use of growth factors have shown to enhance healing in MRONJ patients. Implementing these methods alone or in conjunction with surgical treatment has been linked to reduced discomfort and improved wound healing and increased new bone formation.
DISCUSSION
While several adjuvant treatment modalities exhibit promising results in facilitating the healing process, current clinical practice guidelines predominantly recommend antibiotic therapy as a non-surgical approach, primarily addressing secondary infections in necrotic areas. However, this mainly addresses the potential infectious complication of MRONJ. Medical approaches including PENT-E, teriparatide, PBM, and PDT can result in successful management and should be considered prior to taking a surgical approach. Combined medical management for both preventing and managing MRONJ holds potential for achieving optimal clinical outcomes and avoiding surgical intervention, requiring further validation through larger studies and controlled trials.
Topics: Humans; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Combined Modality Therapy; Osteonecrosis; Teriparatide; Jaw Diseases
PubMed: 38443685
DOI: 10.1007/s00520-024-08388-4 -
Indian Journal of Otolaryngology and... Feb 2024Bell's palsy is an acute, unilateral, lower motor neuron peripheral facial paralysis. It is the most common cause of facial paralysis in the ages ranging from 13 to 65...
BACKGROUND AND AIMS
Bell's palsy is an acute, unilateral, lower motor neuron peripheral facial paralysis. It is the most common cause of facial paralysis in the ages ranging from 13 to 65 years. It not only causes physical disfigurement of face but is also associated with social stigma and psychological trauma to the patient. In Bell's Palsy, there is hypoxic damage to the nerve due to reduced blood flow and cellular injury to the capillaries. Pentoxifylline is a phosphodiesterase inhibitor that increases the cAMP and cGMP levels at the site of the RBC cell membrane thereby improving the dexterity of the cell membrane allowing the RBCs to pass through the damaged and narrowed blood vessels thereby improving the perfusion and oxygen delivery to the damaged tissues. Vasoactive agents are not routinely used as an active component in the treatment. Since vascular compromise plays a predominant role in the pathophysiology of Bell's palsy, it is proposed that the addition of a vasoactive agent like Pentoxifylline can improve the recovery rate and shorten the duration of treatment in the management of Bell's Palsy.
MATERIALS AND METHODS
The study was conducted in the Department of ENT, BMCRI, Bangalore during the period February 2021 to August 2022. This is a prospective randomized control study which included 70 patients attending the out-patient department of ENT, Bangalore Medical College and Research Institute, Bangalore. Written informed consent was taken from all patients included in the study. A detailed history, thorough clinical examination, and relevant investigations were done for these patients. Patients were randomly divided into Group A and Group B based on random numbers generated by the WINPEPI software version 11.65. The study group (Group A) received standard treatment in addition to Tab Pentoxifylline 400 mg TID for 1 week. The control group (Group B) received only the standard treatment regimen. Patients were followed up on Days 5, 10, 15, and 6 months to assess recovery following treatment. The recovery of facial nerve function was evaluated as per the House-Brackmann Grading system for any improvement. Both pre-treatment and post-treatment HB grades were analyzed. The data collected were tabulated and subjected to statistical analysis using ANOVA.
RESULTS
The age distribution of the patients showed that the most common age group affected in this study was 18-30 years. Males were affected more than females (1.2:1). The most common HB grade at presentation noted in this study was Grade 4 in both groups (54.2%). At the beginning of the treatment, in Group A, around 43% patients had HB grade of 3 and 57% patients had HB grade of 4. In Group B, around 20% patients had HB grade 2, 28.57% patients with grade 3 and 51.43% patients with grade 4. After a follow-up period of 6 months, in Group A, around 43% of patients achieved a HB grade of 1, 51% patients achieved a grade of 2 and about 6% patients had a grade of 3. In Group B after a follow up period of 6 months, 29% patients achieved HB grade of 1, 46% patients achieved grade of 2 and 26% patients had a grade of 3. It was observed that of patients had better outcomes (Normal facial function) in Group A (Study group) compared to of patients in Group B (Control group). It is evident that a patient who presented with HB grades of 2 or 3 and who presented within 5 days had better chances of recovery which was statistically significant ).
INTERPRETATION AND CONCLUSION
From the present study, it may be concluded that Bell's palsy occurs in all age groups. It affects younger age groups more commonly (2nd decade) and affects males more than females. The study group who had received Tab Pentoxifylline along with standard treatment had better outcome. This highlights the benefit of vasoactive agent in the management of Bell's palsy by improving the oxygen delivery to the affected tissues.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s12070-023-04298-9.
PubMed: 38440638
DOI: 10.1007/s12070-023-04298-9 -
European Journal of Obstetrics &... Mar 2024This study evaluated the effects of high-intensity interval training (HIIT), moderate-intensity continuous training (MICT), and pentoxifylline (PTX) on coagulation...
OBJECTIVES
This study evaluated the effects of high-intensity interval training (HIIT), moderate-intensity continuous training (MICT), and pentoxifylline (PTX) on coagulation factors, including the amount and percentage of lymphocytes, PLC, PLR, aPTT, PT, PT.I.N. R in a model of rats with endometriosis.
METHODS
Endometriosis was surgically induced in female Sprague-Dawley rats. The rats with confirmed endometrial implants were divided into control, MICT, pentoxifylline (D), HIIT+D, and MICT+D, HIIT groups. D and exercise interventions were performed for eight weeks. Then, the macroscopic size of endometriosis lesions was measured, and inflammatory factors (count and percentage of lymphocytes) and coagulation factors, including PLC, PLR, aPTT, PT, PT.I.N. R, and PLR in blood samples were evaluated.
RESULTS
D significantly decreased the volume of lesions and significantly increased PT and PT.I.N. R in blood. HIIT decreased the volume of lesions and significantly increased PT. MICT did not cause significant effects on the target variables. MICT+D decreased the volume of lesions. HIIT+D significantly decreased the volume of lesions and PLC and increased aPTT as well as the count and percentage of lymphocytes, PT, and PT.I.N. R, and decreased PLR.
CONCLUSIONS
All interventions(except for MICT) especially HIIT+D and D by priority, induced a significant effect on reducing some indices of inflammation and coagulation.
PubMed: 38419652
DOI: 10.1016/j.eurox.2024.100292 -
The Cochrane Database of Systematic... Feb 2024Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity that causes progressive constriction of the cheeks and mouth accompanied by severe pain and reduced... (Review)
Review
BACKGROUND
Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity that causes progressive constriction of the cheeks and mouth accompanied by severe pain and reduced mouth opening. OSF has a significant impact on eating and swallowing, affecting quality of life. There is an increased risk of oral malignancy in people with OSF. The main risk factor for OSF is areca nut chewing, and the mainstay of treatment has been behavioural interventions to support habit cessation. This review is an update of a version last published in 2008.
OBJECTIVES
To evaluate the benefits and harms of interventions for the management of oral submucous fibrosis.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 5 September 2022.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) of adults with a biopsy-confirmed diagnosis of OSF treated with systemic, locally delivered or topical drugs at any dosage, duration or delivery method compared against placebo or each other. We considered surgical procedures compared against other treatments or no active intervention. We also considered other interventions such as physiotherapy, ultrasound or alternative therapies.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. participant-reported resumption of normal eating, chewing and speech; 2. change or improvement in maximal mouth opening (interincisal distance); 3. improvement in range of jaw movement; 4. change in severity of oral/mucosal burning pain/sensation; 5.
ADVERSE EFFECTS
Our secondary outcomes were 6. quality of life; 7. postoperative discomfort or pain as a result of the intervention; 8. participant satisfaction; 9. hospital admission; 10. direct costs of medication, hospital bed days and any associated inpatient costs for the surgical interventions. We used GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We included 30 RCTs (2176 participants) in this updated review. We assessed one study at low risk of bias, five studies at unclear risk of bias and 24 studies at high risk of bias. We found diverse interventions, which we categorised according to putative mechanism of action. We present below our main findings for the comparison 'any intervention compared with placebo or no active treatment' (though most trials included habit cessation for all participants). Results for head-to-head comparisons of active interventions are presented in full in the main review. Any intervention versus placebo or no active treatment Participant-reported resumption of normal eating, chewing and speech No studies reported this outcome. Interincisal distance Antioxidants may increase mouth opening (indicated by interincisal distance (mm)) when measured at less than three months (mean difference (MD) 3.11 mm, 95% confidence interval (CI) 0.46 to 5.77; 2 studies, 520 participants; low-certainty evidence), and probably increase mouth opening slightly at three to six months (MD 8.83 mm, 95% CI 8.22 to 9.45; 3 studies, 620 participants; moderate-certainty evidence). Antioxidants may make no difference to interincisal distance at six-month follow-up or greater (MD -1.41 mm, 95% CI -5.74 to 2.92; 1 study, 90 participants; low-certainty evidence). Pentoxifylline may increase mouth opening slightly (MD 1.80 mm, 95% CI 1.02 to 2.58; 1 study, 106 participants; low-certainty evidence). However, it should be noted that these results are all less than 10 mm, which could be considered the minimal change that is meaningful to someone with oral submucous fibrosis. The evidence was very uncertain for all other interventions compared to placebo or no active treatment (intralesional dexamethasone injections, pentoxifylline, hydrocortisone plus hyaluronidase, physiotherapy). Burning sensation Antioxidants probably reduce burning sensation visual analogue scale (VAS) scores at less than three months (MD -30.92 mm, 95% CI -31.57 to -30.27; 1 study, 400 participants; moderate-certainty evidence), at three to six months (MD -70.82 mm, 95% CI -94.39 to -47.25; 2 studies, 500 participants; moderate-certainty evidence) and at more than six months (MD -27.60 mm, 95% CI -36.21 to -18.99; 1 study, 90 participants; moderate-certainty evidence). The evidence was very uncertain for the other interventions that were compared to placebo and measured burning sensation (intralesional dexamethasone, vasodilators). Adverse effects Fifteen studies reported adverse effects as an outcome. Six of these studies found no adverse effects. One study evaluating abdominal dermal fat graft reported serious adverse effects resulting in prolonged hospital stay for 3/30 participants. There were mild and transient general adverse effects to systemic drugs, such as dyspepsia, abdominal pain and bloating, gastritis and nausea, in studies evaluating vasodilators and antioxidants in particular.
AUTHORS' CONCLUSIONS
We found moderate-certainty evidence that antioxidants administered systemically probably improve mouth opening slightly at three to six months and improve burning sensation VAS scores up to and beyond six months. We found only low/very low-certainty evidence for all other comparisons and outcomes. There was insufficient evidence to make an informed judgement about potential adverse effects associated with any of these treatments. There was insufficient evidence to support or refute the effectiveness of the other interventions tested. High-quality, adequately powered intervention trials with a low risk of bias that compare biologically plausible treatments for OSF are needed. It is important that relevant participant-reported outcomes are evaluated.
Topics: Adult; Humans; Oral Submucous Fibrosis; Pentoxifylline; Drug-Related Side Effects and Adverse Reactions; Vasodilator Agents; Abdominal Pain; Antioxidants; Dexamethasone
PubMed: 38415846
DOI: 10.1002/14651858.CD007156.pub3