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Journal of Chromatography. B,... Jun 2024Antiarrhythmic and antihypertensive drugs are frequently encountered in post mortem analysis, and the question may arise as to whether they were administered in...
Antiarrhythmic and antihypertensive drugs are frequently encountered in post mortem analysis, and the question may arise as to whether they were administered in therapeutic doses, and if they were taken in accidental, intentional, or suicidal overdose scenarios. Therefore, a novel analytical method was developed and validated for the quantification of 35 drugs with toxicological relevance, including antihypertensive and antiarrhythmic drugs (ajmaline, amlodipine, amiodarone, atenolol, bisoprolol, carvedilol, clonidine, desethylamiodarone, diltiazem, donepezil, doxazosin, dronedarone, esmolol, flecainide, lercanidipine, lidocaine, metoprolol, nebivolol, nimodipine, pindolol, prajmaline, propafenone, propranolol, sotalol, urapidil, and verapamil), as well as other medications commonly found in combination (sildenafil, tadalafil, atorvastatin, clopidogrel, dapoxetine, memantine, pentoxifylline, rivastigmine, and ivabradine). The method enables simultaneous identification and quantification in blood samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Validation exhibited excellent linearity across the concentration range for all analytes. Precision and accuracy were within acceptable limits, with bias and relative standard deviation (RSD) values consistently below 9 % and 10 %, respectively. Selectivity and specificity assessments confirmed the absence of any interference from contaminants or co-extracted drugs. The method demonstrated very high sensitivity, with limits of detection (LOD) as low as 0.01 ng/ml and limits of quantification (LOQ) as low as 0.04 ng/ml. Extraction recovery exceeded 57.5 % for all analytes except atenolol, and matrix effects were <17 % for all analytes except pindolol. Processed sample stability evaluations revealed consistent results with acceptable deviations for all analytes. In addition, the method was specifically tested for the use in post mortem analysis. The applicability of our method was demonstrated by the analysis of two authentic human autopsy blood samples.
PubMed: 38878710
DOI: 10.1016/j.jchromb.2024.124196 -
International Journal of Surgery Case... Jun 2024Purtscher retinopathy is the rare form of occlusive microvasculopathy, characterized by multiple retinal white areas around the optic nerve head and fovea with...
INTRODUCTION AND IMPORTANCE
Purtscher retinopathy is the rare form of occlusive microvasculopathy, characterized by multiple retinal white areas around the optic nerve head and fovea with paravascular clearing and may be related to intraretinal hemorrhages. Acute Pancreatitis (AP) is one of the most common gastrointestinal reasons for hospital admissions globally. The complications of Acute Pancreatitis may include Purtscher's-like retinopathy, which has a low incidence rate of less than 0.24 instances per million cases. This case report highlights the value of thorough medical history taking and examination, and it apprises the consideration of ophthalmological manifestation in patients of Acute Pancreatitis.
CASE PRESENTATION
A 34-year-old female came to the emergency room due to intense abdominal pain associated with nausea and vomiting, which worsened over the last 24 h. The pain was described as continuous, sharp, and cramping-like in the upper abdomen, radiating to the back. Lab tests revealed elevated serum amylase and lipase levels, indicating pancreatitis, along with slight leukocytosis. A contrast-enhanced CT scan confirmed acute pancreatitis with mild inflammation and enlargement of the pancreas. Two days after admission, the patient experienced a sudden and painless loss of central vision in both eyes. There was no history of trauma or any other significant relevant history, other than pancreatitis. The ophthalmologist's examination found reduced visual acuity (6/60 in the right eye, 3/60 in the left eye), normal corneas, and anterior chambers.
DISCUSSION
Inkeles and Walsh established the first link between acute pancreatitis and Purtscher-like retinopathy when they reported three cases of the distinctive retinal appearance in individuals with acute pancreatitis in 1975.
CONCLUSION
The recovery and prognosis in cases of Purtscher-like retinopathy is variable and further research is required to ascertain the usage of corticosteroids and pentoxifylline in improving the course of a patient's with Purtscher's-like retinopathy.
PubMed: 38875828
DOI: 10.1016/j.ijscr.2024.109881 -
Cancer Drug Resistance (Alhambra,... 2024Multidrug resistance (MDR) is frequent in non-small cell lung cancer (NSCLC) patients, which can be due to its fibrotic stroma. This work explores the combination of...
Multidrug resistance (MDR) is frequent in non-small cell lung cancer (NSCLC) patients, which can be due to its fibrotic stroma. This work explores the combination of pentoxifylline, an anti-fibrotic and chitinase 3-like-1 (CHI3L1) inhibitor drug, with conventional chemotherapy to improve NSCLC treatment. The effect of pentoxifylline in the expression levels of P-glycoprotein (P-gp), CHI3L1 and its main downstream proteins, as well as on cell death, cell cycle profile, and P-gp activity was studied in two pairs of sensitive and MDR counterpart NSCLC cell lines (NCI-H460/NCI-H460/R and A549/A549-CDR2). Association studies between gene expression and NSCLC patients' survival were performed using The Cancer Genome Atlas (TCGA) analysis. The sensitizing effect of pentoxifylline to different drug regimens was evaluated in both sensitive and MDR NSCLC cell lines. The cytotoxicity of the drug combinations was assessed in MCF10A non-tumorigenic cells. Pentoxifylline slightly decreased the expression levels of CHI3L1, β-catenin and signal transducer and activator of transcription 3 (STAT3), and caused a significant increase in the G1 phase of the cell cycle in both pairs of NSCLC cell lines. A significant increase in the % of cell death was observed in the sensitive NCI-H460 cell line. TCGA analysis revealed that high levels of CHI3L1 are associated with low overall survival (OS) in NSCLC patients treated with vinorelbine. Moreover, pentoxifylline sensitized both pairs of sensitive and MDR NSCLC cell lines to the different drug regimens, without causing significant toxicity to non-tumorigenic cells. This study suggests the possibility of combining pentoxifylline with chemotherapy to increase NSCLC therapeutic response, even in cases of MDR.
PubMed: 38835347
DOI: 10.20517/cdr.2024.04 -
Archives of Razi Institute Dec 2023Pentoxifylline (PTXF) is a vasoactive agent that plays a significant role in the treatment of thin-layer endometrium cases. The PTXF, also identified as oxpentifylline,...
Pentoxifylline (PTXF) is a vasoactive agent that plays a significant role in the treatment of thin-layer endometrium cases. The PTXF, also identified as oxpentifylline, is a member of xanthine derivatives and a competitive nonselective phosphodiesterase inhibitor leading to the elevation of intracellular cAMP, inhibition of tumor necrosis factor and leukotriene synthesis, activation of protein kinase A, and reduction of inflammation and innate immunity. Moreover, it is used as an agent to relieve muscle pain in people with peripheral artery disease (vascular irregularities). It is also an acceptable choice for the treatment of radiation-induced fibrosis. Therefore, the present study aimed to determine the advantageous impact of PTXF and PTXF-loaded poly lactic-co-glycolic acid (PLGA) on female rats after being exposed to ethanol to create a thin layer of the endometrium. For this purpose, 50 female rats were selected and divided into five groups (G1: negative normal control, G2: positive control, G3: PLGA only, G4: preference PTXF, and G5: PLGA-PTXF groups) for a 20-day treatment period. In this study, the histopathological section revealed a perfect improvement in the tissues of the uterine horn of female rats that induced endometria and were treated with PLGA-PTXF. In this group of rats, clear healing was achieved and there was an increase in the thickness of endometrium and myometrium, compared to the ordinary PTXF-treated group which had the lowest recovery characteristics. However, the positive control group underwent a significant decrease in terms of endometrium and myometrium thickness as well as vascular and glandular density. This study showed that the PTXF-loaded PLGA had the capacity to heal the thin layer of the endometrium by improving the levels of histopathological changes, especially regarding the thickness of the endometrium and myometrium more than the ordinary PTXF.
Topics: Pentoxifylline; Animals; Female; Rats; Endometrium; Polylactic Acid-Polyglycolic Acid Copolymer; Rats, Wistar
PubMed: 38828173
DOI: 10.32592/ARI.2023.78.6.1762 -
Alternative Therapies in Health and... May 2024To explore the efficacy of dapagliflozin plus pentoxifylline in the treatment of early diabetic nephropathy and its effect on serum inflammatory factors and immune...
OBJECTIVE
To explore the efficacy of dapagliflozin plus pentoxifylline in the treatment of early diabetic nephropathy and its effect on serum inflammatory factors and immune function.
METHODS
A total of 90 patients with early diabetic nephropathy who were admitted to Cangzhou Central Hospital from January 2019 to January 2022 were recruited and randomized (1:1) into a control group and an observation group using the random number table method. The control group was treated with dapagliflozin, and the observation group was treated with pentoxifylline plus dapagliflozin. The effectiveness of urinary α (1) microglobulin (α 1-mg) was determined by immunoturbidimetric method, and urinary β (2) microglobulin (β 2-mg) was determined. Urine creatinine was determined enzymatically, and the urinary microprotein albumin creatinine ratio (mAlb/Cr) was calculated. The levels of inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)] were detected. Before and after treatment, 3 mL of venous blood was drawn from the two groups of patients, and serum CD4+, CD8+, and CD4+/CD8+ levels were detected. The incidence of adverse reactions between the two groups was calculated.
RESULTS
Dapagliflozin plus pentoxifylline was associated with a higher effective rate than dapagliflozin alone (96.67% vs 81.67%) (RR 0·80 [95% CI 0·61-0.98]; P = .021). Dapagliflozin plus pentoxifylline led to lower renal function parameters versus dapagliflozin alone, in favor of the observation group (RR 0.67 [95% CI 0.66-0.88]; P = .032). After treatment, the serum levels of IL-6 and TNF-α in patients treated with dapagliflozin plus pentoxifylline were lower than counterparts treated with dapagliflozin (RR 0.62 [95% CI 0.51-0.78]; P = .037). After treatment, CD4+ and CD4+/CD8+ in the two groups were increased compared with baseline parameters, and the level of CD8+ was decreased ; the increase and decrease were greater in the observation group than in the control group (RR 0.70 [95% CI 0.71-0.96]; P = .044) (RR 0.53 [95% CI 0.41-0.78]; P = .033). The two groups demonstrated similar safety profiles with no statistical difference observed in the incidence of adverse reactions between the two groups (RR 0.73 [95% CI 0.73-1.08]; P = .051).
CONCLUSION
Dapagliflozin plus pentoxifylline might be a promising alternative in the treatment of patients with early diabetic nephropathy, it significantly mitigates the body's inflammatory response, enhances immune function, attenuates the main clinical symptoms, with a high safety profile.
PubMed: 38819176
DOI: No ID Found -
Future Science OA 2024ST-elevation myocardial infarction (STEMI) patients suffer higher mortality and adverse outcomes linked to endothelial dysfunction (ED). 43 patients were randomized to...
ST-elevation myocardial infarction (STEMI) patients suffer higher mortality and adverse outcomes linked to endothelial dysfunction (ED). 43 patients were randomized to pentoxifylline (PTX) 400 mg thrice daily (n = 22) or placebo (n = 21). Soluble vascular cell adhesion molecule-1, malondialdehyde, interleukin-1 (IL-1), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α) were assessed at baseline and 2 months. After 2 months, no significant difference was observed in markers' levels between the 2 groups. However, a within-group comparison revealed a statistically significant change in hs-CRP in the PTX group (10.057 (9.779-10.331) versus 9.721 (6.102-10.191)), p = 0.032. PTX for 2 months in STEMI patients was safe and well-tolerated but had no significant detectable effect on ED, oxidative stress or inflammatory markers. NCT04367935 (ClinicalTrials.gov).
PubMed: 38817362
DOI: 10.2144/fsoa-2023-0266 -
Frontiers in Endocrinology 2024Although the effectiveness of pentoxifylline (PF) as a selective inhibitor of phosphodiesterase to enhance sperm motility through increasing cyclic nucleotide in cases...
INTRODUCTION
Although the effectiveness of pentoxifylline (PF) as a selective inhibitor of phosphodiesterase to enhance sperm motility through increasing cyclic nucleotide in cases of absolute asthenozoospermia has been demonstrated for ICSI, data related to babies born from the PF-ICSI are still severely lacking. Concerns have been raised regarding the potential embryotoxicity of PF due to the controversial results obtained from the analysis of this compound on animal embryo development. This study aimed to determine whether the application of PF to trigger frozen-thawed TESA (testicular sperm aspiration) spermatozoa increases the risk of adverse obstetric and neonatal outcomes compared with non-PF frozen-thawed TESA ICSI and conventional ICSI using fresh ejaculation.
MATERIALS AND METHODS
A total of 5438 patients were analyzed in this study, including 240 patients underwent PF-TESA ICSI (ICSI using PF triggered frozen-thawed testicular spermatozoa), 101 patients underwent non-PF TESA ICSI (ICSI using frozen-thawed testicular spermatozoa) and 5097 patients underwent conventional ICSI using fresh ejaculation. Propensity score matching was executed to control the various characteristics of patients.
RESULTS
No significant differences in pregnancy outcomes were observed among the three groups (PF-TESA ICSI, non-PF TESA ICSI and conventional ICSI), including biochemical pregnancy, clinical pregnancy, implantation, miscarriage, ectopic pregnancy, multiple pregnancy, and live birth, following propensity score matching. Additionally, neonatal outcomes were found to be similar among the three groups, with no statistical differences observed in the birth defect, birth weight, gestational age, preterm birth, and early-neonatal death.
DISCUSSION AND CONCLUSION
PF-ICSI may be an alternative treatment in patients using frozen-thawed testicular spermatozoa, resulting in comparable pregnancy and neonatal outcomes.
Topics: Humans; Pentoxifylline; Pregnancy; Female; Male; Sperm Injections, Intracytoplasmic; Adult; Pregnancy Outcome; Spermatozoa; Cryopreservation; Infant, Newborn; Pregnancy Rate; Sperm Retrieval; Retrospective Studies; Semen Preservation
PubMed: 38812814
DOI: 10.3389/fendo.2024.1364285 -
International Journal of Molecular... May 2024Three-dimensional cell cultures have improved the evaluation of drugs for cancer therapy, due to their high similarity to solid tumors. In melanoma, autophagy appears to...
Three-dimensional cell cultures have improved the evaluation of drugs for cancer therapy, due to their high similarity to solid tumors. In melanoma, autophagy appears to show a dual role depending on the progression of the disease. p62 protein has been proposed for the evaluation of autophagic flux since its expression is an indicator of the state of autophagy. Pentoxifylline (PTX) and Norcantharidin (NCTD) are drugs that have been shown to possess anticancer effects. In this work, we used B16F1 mouse melanoma cells in two-dimensional (2D) monolayer cultures and three-dimensional (3D) spheroids to test the effect of PTX and NCTD over the p62 expression. We analyzed the effect on p62 expression through Western blot and immunofluorescence assays. Our results indicate that PTX decreases p62 expression in both cell culture models, while Norcantharidin increases its expression in 3D cultures at 24 h. Therefore, these drugs could have a potential therapeutic use for the regulation of autophagy in melanoma, depending on the state of evolution of the disease.
Topics: Bridged Bicyclo Compounds, Heterocyclic; Animals; Mice; Pentoxifylline; Autophagy; Cell Line, Tumor; Melanoma, Experimental; Cell Culture Techniques; Sequestosome-1 Protein; Antineoplastic Agents; Spheroids, Cellular
PubMed: 38791178
DOI: 10.3390/ijms25105140 -
Cureus Apr 2024This case report presents a unique instance of ascites in acute alcoholic hepatitis (AH) occurring in a non-cirrhotic patient. Comprehensive diagnostic evaluation...
This case report presents a unique instance of ascites in acute alcoholic hepatitis (AH) occurring in a non-cirrhotic patient. Comprehensive diagnostic evaluation excluded alternative etiologies, pinpointing sinusoidal non-cirrhotic portal hypertension. Present therapeutic modalities for AH, including steroids and pentoxifylline, offer limited efficacy, necessitating ongoing investigation. Liver transplantation may be contemplated in refractory cases. This case underscores the intricate nature of AH presentations and the challenges in their management, emphasizing the imperative need for continued research to delineate optimal therapeutic strategies. Early intervention remains pivotal in addressing AH complications, underscoring the need for heightened clinical vigilance and proactive treatment approaches in such cases.
PubMed: 38741864
DOI: 10.7759/cureus.58187 -
Dentistry Journal Mar 2024Osteoradionecrosis of the jaw is a morbid complication of radiotherapy in patients with oral and oropharyngeal cancers that may be precipitated by dental extractions....
Prophylactic Use of Pentoxifylline and Tocopherol for Prevention of Osteoradionecrosis of the Jaw after Dental Extraction in Post-Radiated Oral and Oropharyngeal Cancer Patients: An Initial Case Series.
Osteoradionecrosis of the jaw is a morbid complication of radiotherapy in patients with oral and oropharyngeal cancers that may be precipitated by dental extractions. Pentoxifylline and tocopherol (PENTO) has been utilized in the management of osteoradionecrosis and as prophylaxis for post-radiated head and neck oncology patients requiring an invasive dental procedure. This observational study aims to report the outcome of the prophylactic use of PENTO in the prevention of osteoradionecrosis of the jaw after dental extractions in post-radiated oral and oropharyngeal cancer patients and to review the current literature on this topic. Four post-radiated oral and oropharyngeal oncology patients were referred to the dental oncology clinic of the University Dental Practice, University of Tennessee Health Sciences Center for dental extractions. All four patients were prescribed pentoxifylline 400 mg BID (twice a day) and tocopherol 400 IU BID (oral tablets) for 2 weeks before extraction(s) and for 6 weeks after extraction(s). All patients were followed up every week after the second week post-extraction if feasible until the extraction site(s) healed (covered by mucosa). The assessment endpoint was defined as 6 weeks post-extraction with the outcomes assessed as using four categories determined by the area of exposed bone: complete healing (complete mucosal coverage of extraction site); partial healing (reduction in size of extraction site); no change; and progression (increase in size of the extraction site). At the assessment endpoint, all patients had complete healing of all extraction sites. The ORN rate at the patient level (0/4) and individual tooth level (0/8) was 0%. All patients tolerated the PENTO medications and no adverse effects from the use of these medications were reported. This limited study in addition to the other reviewed studies estimates the rate of ORN at the patient level as 3.2% (14/436) for post-radiated head and neck oncology patients after dental extractions/invasive oral procedures. In conclusion, this PENTO regimen can reduce/prevent the incidence of ORN in post-radiated head and neck oncology patients. This safe and cost-effective protocol (PENTO regimen) should be further evaluated as prophylaxis for post-radiated head and neck oncology patients requiring an invasive dental procedure. We recommend large prospective studies to be carried out to further validate these findings.
PubMed: 38667995
DOI: 10.3390/dj12040083