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JAAD Case Reports Sep 2023
PubMed: 37593377
DOI: 10.1016/j.jdcr.2023.07.002 -
Drugs in R&D Sep 2023At present, the therapies of dilated cardiomyopathy concentrated on the symptoms of heart failure and related complications. The study is to evaluate the clinical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
At present, the therapies of dilated cardiomyopathy concentrated on the symptoms of heart failure and related complications. The study is to evaluate the clinical efficacy of a combination of various conventional and adjuvant drugs in treating dilated cardiomyopathy via network meta-analysis.
METHODS
The study was reported according to the PRISMA 2020 statement. From inception through 27 June 2022, the PubMed, Embase, Cochrane library, and Web of Science databases were searched for randomized controlled trials on medicines for treating dilated cardiomyopathy. The quality of the included studies was evaluated according to the Cochrane risk of bias assessment. R4.1.3 and Revman5.3 software were used for analysis.
RESULTS
There were 52 randomized controlled trials in this study, with a total of 25 medications and a sample size of 3048 cases. The network meta-analysis found that carvedilol, verapamil, and trimetazidine were the top three medicines for improving left ventricular ejection fraction (LVEF). Ivabradine, bucindolol, and verapamil were the top 3 drugs for improving left ventricular end-diastolic dimension (LVEDD). Ivabradine, L-thyroxine, and atorvastatin were the top 3 drugs for improving left ventricular end-systolic dimension (LVESD). Trimetazidine, pentoxifylline, and bucindolol were the top 3 drugs for improving the New York Heart Association classification (NYHA) cardiac function score. Ivabradine, carvedilol, and bucindolol were the top 3 drugs for reducing heart rate (HR).
CONCLUSION
A combination of different medications and conventional therapy may increase the clinical effectiveness of treating dilated cardiomyopathy. Beta-blockers, especially carvedilol, can improve ventricular remodeling, cardiac function, and clinical efficacy in patients with dilated cardiomyopathy (DCM). Hence, they can be used if patients tolerate them. If LVEF and HR do not meet the standard, ivabradine can also be used in combination with other treatments. However, since the quality and number of studies in our research were limited, large sample size, multi-center, and high-quality randomized controlled trials are required to corroborate our findings.
Topics: Humans; Cardiomyopathy, Dilated; Carvedilol; Ivabradine; Stroke Volume; Trimetazidine; Network Meta-Analysis; Ventricular Function, Left; Verapamil; Randomized Controlled Trials as Topic
PubMed: 37556093
DOI: 10.1007/s40268-023-00435-5 -
Crystal Growth & Design Aug 2023Quercetin (QUE) is a widely studied nutraceutical with a number of potential therapeutic properties. Although QUE is abundant in the plant kingdom, its poor solubility...
Quercetin (QUE) is a widely studied nutraceutical with a number of potential therapeutic properties. Although QUE is abundant in the plant kingdom, its poor solubility (≤20 μg/mL) and poor oral bioavailability have impeded its potential utility and clinical development. In this context, cocrystallization has emerged as a useful method for improving the physicochemical properties of biologically active molecules. We herein report a novel cocrystal of the nutraceutical quercetin (QUE) with the coformer pentoxifylline (PTF) and a solvate of a previously reported structure between QUE and betaine (BET). We also report the outcomes of in vitro and in vivo studies of QUE release and absorption from a panel of QUE cocrystals: betaine (BET), theophylline (THP), l-proline (PRO), and novel QUEPTF. All cocrystals were found to exhibit an improvement in the dissolution rate of QUE. Further, the QUE plasma levels in Sprague-Dawley rats showed a 64-, 27-, 10- and 7-fold increase in oral bioavailability for QUEBET·MeOH, QUEPTF, QUEPRO, and QUETHP, respectively, compared to QUE anhydrate. We rationalize our in vivo and in vitro findings as the result of dissolution-supersaturation-precipitation behavior.
PubMed: 37547881
DOI: 10.1021/acs.cgd.3c00590 -
Trials Aug 2023Venous leg ulcers (VLUs) are the most severe manifestation of chronic venous disease, with long healing time and a high recurrence rate. It imposes a heavy burden on...
BACKGROUND
Venous leg ulcers (VLUs) are the most severe manifestation of chronic venous disease, with long healing time and a high recurrence rate. It imposes a heavy burden on patients, their families, and the health care system. Chronic inflammation triggered by sustained venous hypertension is now recognized as the hallmark of chronic venous disease. The anti-inflammatory effect of pentoxifylline may offer a promising avenue to treat VLUs. However, current evidence of pentoxifylline for VLUs is relatively small and of low quality. The aim of this study is to evaluate the efficacy and safety of pentoxifylline for VLUs in the Chinese population.
METHODS
This is a randomized, double-blinded, double-dummy, multi-center, placebo-controlled clinical trial. A total of 240 patients will be randomized to receive pentoxifylline (400 mg, twice daily) or placebo for 24 weeks. All participants will receive diosmin treatment and standard care of VLUs and other comorbidities. The primary outcome is the difference in the wound healing rate within 12 weeks between pentoxifylline and placebo. Secondary outcomes include (1) percent wound size changes at 12 weeks, (2) the levels of TNF-α and IL-6, (3) venous clinical severity score and chronic venous insufficiency quality of life score, and (4) ulcer recurrence within 24 weeks.
DISCUSSION
This study would evaluate the efficacy and safety of pentoxifylline for VLUs in the Chinese population. If confirmed, it wound offer another effective and safe therapeutic option for treatment of VLUs.
TRIAL REGISTRATION
The trial was registered at the Chinese Clinical Trial Registry (No. ChiCTR-2100053053). Registered on 10 November, 2021, https://www.chictr.org.cn/showproj.aspx?proj=137010.
Topics: Humans; Pentoxifylline; Quality of Life; Varicose Ulcer; Wound Healing; Venous Insufficiency; Leg Ulcer; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 37533132
DOI: 10.1186/s13063-023-07547-y -
Journal of Clinical Medicine Jul 2023Medication-related osteonecrosis of the jaws (MRONJ) is a challenging situation in clinics. Previous studies have shown that pentoxifylline combined with tocopherol...
Outcomes of a Pharmacological Protocol with Pentoxifylline and Tocopherol for the Management of Medication-Related Osteonecrosis of the Jaws (MRONJ): A Randomized Study on 202 Osteoporosis Patients.
Medication-related osteonecrosis of the jaws (MRONJ) is a challenging situation in clinics. Previous studies have shown that pentoxifylline combined with tocopherol proved to be beneficial in patients with osteoradionecrosis, due to their antioxidant and antifibrotic properties. The aim of this randomized study was to evaluate the effect of pentoxifylline and tocopherol in patients that had developed MRONJ after tooth extractions. The study population consisted of 202 Stage I MRONJ female patients with an average age of 66.4 ± 8.3 years, who were divided into two groups. The test group (n = 108) received a pharmacological protocol with pentoxifylline and tocopherol (2 months pre-operatively and 6 months post-operatively). The control group (n = 94) had sequestrectomy operations without any pharmacological preparation. The main outcomes were clinical healing of the mucosa after 1 month, and clinical and radiographic healing of the bone lesion at 6 months. In the test group all patients had mucosal healing and there was only one relapse within 6 months. In the control group, in 17% of the patients the mucosa did not heal, 71% of the patients relapsed within two months, and 7% developed infectious complications (such as abscess or phlegmon). After 6 months, the control group patients with persisting issues were prescribed pentoxifylline and tocopherol, as in the test group. At a subsequent follow-up, all those patients healed completely. Patients were monitored for a period of 7.8 ± 0.3 years, during which no relapse or additional problems were reported. As a conclusion, pentoxifylline and tocopherol protocol seems to be beneficial in the management of MRONJ patients.
PubMed: 37510777
DOI: 10.3390/jcm12144662 -
Journal of Experimental & Clinical... Jul 2023Approximately 20-50% of patients presenting with localized colorectal cancer progress to stage IV metastatic disease (mCRC) following initial treatment and this is a...
BACKGROUND
Approximately 20-50% of patients presenting with localized colorectal cancer progress to stage IV metastatic disease (mCRC) following initial treatment and this is a major prognostic determinant. Here, we have interrogated a heterogeneous set of primary colorectal cancer (CRC), liver CRC metastases and adjacent liver tissue to identify molecular determinants of the colon to liver spreading. Screening Food and Drug Administration (FDA) approved drugs for their ability to interfere with an identified colon to liver metastasis signature may help filling an unmet therapeutic need.
METHODS
RNA sequencing of primary colorectal cancer specimens vs adjacent liver tissue vs synchronous and asynchronous liver metastases. Pathways enrichment analyses. The Library of Integrated Network-based Cellular Signatures (LINCS)-based and Connectivity Map (CMAP)-mediated identification of FDA-approved compounds capable to interfere with a 22 gene signature from primary CRC and liver metastases. Testing the identified compounds on CRC-Patient Derived Organoid (PDO) cultures. Microscopy and Fluorescence Activated Cell Sorting (FACS) based analysis of the treated PDOs.
RESULTS
We have found that liver metastases acquire features of the adjacent liver tissue while partially losing those of the primary tumors they derived from. We have identified a 22-gene signature differentially expressed among primary tumors and metastases and validated in public databases. A pharmacogenomic screening for FDA-approved compounds capable of interfering with this signature has been performed. We have validated some of the identified representative compounds in CRC-Patient Derived Organoid cultures (PDOs) and found that pentoxyfilline and, to a minor extent, dexketoprofen and desloratadine, can variably interfere with number, size and viability of the CRC -PDOs in a patient-specific way. We explored the pentoxifylline mechanism of action and found that pentoxifylline treatment attenuated the 5-FU elicited increase of ALDHhigh cells by attenuating the IL-6 mediated STAT3 (tyr705) phosphorylation.
CONCLUSIONS
Pentoxifylline synergizes with 5-Fluorouracil (5-FU) in attenuating organoid formation. It does so by interfering with an IL-6-STAT3 axis leading to the emergence of chemoresistant ALDHhigh cell subpopulations in 5-FU treated PDOs. A larger cohort of CRC-PDOs will be required to validate and expand on the findings of this proof-of-concept study.
Topics: Humans; Colorectal Neoplasms; Interleukin-6; Pentoxifylline; Fluorouracil; Liver Neoplasms; Organoids
PubMed: 37460938
DOI: 10.1186/s13046-023-02754-6 -
International Journal of Molecular... Jun 2023Cervical cancer (CC) is one of the most common and deadly types of female cancer worldwide. Late diagnosis in CC increases the risk of tumor cells spreading to distant...
Cervical cancer (CC) is one of the most common and deadly types of female cancer worldwide. Late diagnosis in CC increases the risk of tumor cells spreading to distant organs (metastasis). The epithelial-mesenchymal transition (EMT) is a fundamental process of cancer metastasis. Inflammation can lead to tumor progression, EMT induction, and metastasis. The inflammatory microenvironment is a potent inducer of EMT; inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-α) and Transforming growth factor-beta (TGF-β1) activate transcriptional factors such as STAT3, Snail, Smad, and the Nuclear Factor kappa light-chain-enhancer of activated beta cells (NF-κΒ), which drive EMT. Anti-inflammatory compounds may be an option in the disruption of EMT. PenToXifylline (PTX) possesses potent anti-inflammatory effects by inhibiting NF-κB activity. In addition, PTX exerts an anti-fibrotic effect by decreasing Smad2/3/4. We hypothesize that PTX could exert anti-EMT effects. CaSki human cervical tumor cells were exposed to TNF-α 10 ng/mL and TGF-β1 alone or in combination for 5 days. Our results revealed that TNF-α and TGF-β1 induced N-cadherin and Vimentin, confirming the induction of EMT. Furthermore, the combination of cytokines synergized the expression of mesenchymal proteins, enhanced IκBα and p65 phosphorylation, and upregulated Serpin family E member 1 () mRNA. PTX pretreatment prior to the addition of TNF-α and TGF-β1 significantly reduced N-cadherin and Vimentin levels. To our knowledge, this is the first time that this effect of PTX has been reported. Additionally, PTX reduced the phosphorylation of IκB-α and p65 and significantly decreased expression, cell proliferation, migration, and invasion. In conclusion, PTX may counteract EMT in cervical cancer cells by decreasing the NF-κB and .
Topics: Female; Humans; NF-kappa B; Tumor Necrosis Factor-alpha; Transforming Growth Factor beta1; Epithelial-Mesenchymal Transition; Vimentin; Pentoxifylline; Uterine Cervical Neoplasms; Cadherins; Cell Line, Tumor; Tumor Microenvironment; Plasminogen Activator Inhibitor 1
PubMed: 37445768
DOI: 10.3390/ijms241310592 -
Case Reports in Vascular Medicine 2023Livedoid vasculopathy is a thromboocclusive cutaneous vasculopathy manifested by livedoid changes, atrophie blanche, and ulceration. The pathogenesis is speculated to...
Livedoid vasculopathy is a thromboocclusive cutaneous vasculopathy manifested by livedoid changes, atrophie blanche, and ulceration. The pathogenesis is speculated to involve increasing coagulation or impaired thrombolysis leading to the occlusion of dermal blood vessels with fibrin thrombi. Livedoid vasculopathy is known to primarily affect the lower extremities. We report the first case of livedoid vasculopathy affecting the penis. A 60-year-old male was evaluated for a split urine stream with associated irritation and peeling of the skin of the glans penis. His penile ulcer continued to enlarge despite steroids and antibiotics. Due to diagnostic uncertainty, a biopsy was performed which revealed hyaline thrombi within the lumens of small vessels within the upper to mid dermis, fibrinoid material in the walls of these blood vessels and within the perivascular stroma with overlying and adjacent epidermal spongiosis, and mild perivascular lymphocytic infiltrate with a few scattered neutrophils most consistent with livedoid vasculitis. He was started on aspirin and pentoxifylline with limited improvement and was later started on apixaban with near-complete resolution in 6 months. Penile livedoid vasculopathy has not been previously reported in the English literature. Early diagnosis and treatment are imperative to limit morbidity.
PubMed: 37440957
DOI: 10.1155/2023/6920383 -
BMC Urology Jul 2023Post-circumcision penile ischemia is a devastating complication. We will present our experience in managing children with various forms of penile ischemia. (Observational Study)
Observational Study
BACKGROUND
Post-circumcision penile ischemia is a devastating complication. We will present our experience in managing children with various forms of penile ischemia.
MATERIALS AND METHODS
This cohort prospective observational and interventional study was performed on all male children with post-circumcision penile ischemia between April 2017 and October 2021. A designed and approved protocol includes a combination of early pentoxifylline infusion, hyperbaric oxygen inhalation, early catheterization, and appropriate surgical debridement were applied for patients with deep ischemia 11/23, mainly the necrotic skin and subcutaneous tissues. Data of patient age, anesthesia method, monopolar diathermy usage, early presentation and positive wound culture were collected and analyzed statistically.
RESULTS
During the study period 3,382 children were circumcised for non-medical reasons; 23 children were diagnosed with penile ischemia (0.7%), among other complications (9%). Most of the penile ischemia is associated with the use of monopolar diathermy (74%). The use of compressive wound dressing to control post-circumcision bleeding and infections is also responsible for ischemia in 52.2% and 43.5% of the cases. Inexperienced physicians were commonly responsible for ischemia (73.9%). Patients managed at first 24 h had better outcomes than those who were presented later (p = 0.001).
CONCLUSION
In children with post-circumcision penile ischemia, a combination of hyperbaric oxygen therapy and pentoxifylline is especially effective for patients with skin and facial necrosis, this management reduces penile tissue loss.
Topics: Child; Humans; Male; Hyperbaric Oxygenation; Circumcision, Male; Pentoxifylline; Penis; Hyperthermia, Induced
PubMed: 37438810
DOI: 10.1186/s12894-023-01284-9 -
Current Obesity Reports Sep 2023To summarize experimental and clinical evidence on the association between tumor necrosis factor-α (TNF-α) and nonalcoholic fatty liver disease (NAFLD) and discuss... (Review)
Review
PURPOSE OF REVIEW
To summarize experimental and clinical evidence on the association between tumor necrosis factor-α (TNF-α) and nonalcoholic fatty liver disease (NAFLD) and discuss potential treatment considerations.
RECENT FINDINGS
Experimental evidence suggests that TNF-α is a cytokine with a critical role in the pathogenesis of NAFLD. Although, the production of TNF-α may be an early event during the course of nonalcoholic fatty liver (NAFL), TNF-α may play a more substantial role in the pathogenesis of nonalcoholic steatohepatitis (NASH) and NAFLD-associated fibrosis. Moreover, TNF-α may potentiate hepatic insulin resistance, thus interconnecting inflammatory with metabolic signals and possibly contributing to the development of NAFLD-related comorbidities, including cardiovascular disease, hepatocellular carcinoma, and extra-hepatic malignancies. In clinical terms, TNF-α is probably associated with the severity of NAFLD; circulating TNF-α gradually increases from controls to patients with NAFL, and then, to patients with NASH. Given this potential association, various therapeutic interventions (obeticholic acid, peroxisome proliferator-activated receptors, sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, probiotics, synbiotics, rifaximin, vitamin E, pentoxifylline, ursodeoxycholic acid, fibroblast growth factor-21, n-3 polyunsaturated fatty acids, statins, angiotensin receptor blockers) have been evaluated for their effect on TNF-α and NAFLD. Interestingly, anti-TNF biologics have shown favorable metabolic and hepatic effects, which may open a possible therapeutic window for the management of advanced NAFLD. The potential key pathogenic role of TNF-α in NAFLD warrants further investigation and may have important diagnostic and therapeutic implications.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Tumor Necrosis Factor-alpha; Tumor Necrosis Factor Inhibitors; Cytokines
PubMed: 37407724
DOI: 10.1007/s13679-023-00519-y