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Biology May 2022Hemorrhagic cystitis is the main adverse effect associated with the clinical use of oxazaphosphorine, resulting in increased oxidative stress and proinflammatory...
Hemorrhagic cystitis is the main adverse effect associated with the clinical use of oxazaphosphorine, resulting in increased oxidative stress and proinflammatory cytokines, which culminate in injury of the bladder tissue. The aim of this study was to evaluate the protective effect of isopropyl gallate (IPG) against ifosfamide (IFOS)-induced hemorrhagic cystitis in mice. The induction of the hemorrhagic cystitis model was carried out using a single dose of IFOS (400 mg/kg, i.p.) four hours after oral pretreatment with IPG (6.25, 12.5, 25, and 50 mg/kg) or saline (vehicle). Mesna (positive control; 80 mg/kg, i.p.) was administered four hours before and eight hours after induction of cystitis. In the present study, IPG 25 mg/kg significantly decreased edema and hemorrhage, with a reduction of the bladder wet weight (36.86%), hemoglobin content (54.55%), and peritoneal vascular permeability (42.94%) in urinary bladders of mice. Interestingly, IPG increased SOD activity (89.27%) and reduced MDA levels (35.53%), as well as displayed anti-inflammatory activity by decreasing TNF-α (88.77%), IL-1β (62.87%), and C-reactive protein (56.41%) levels. Our findings demonstrate that IPG has a substantial protective role against IFOS-induced hemorrhagic cystitis in mice by enhancing antioxidant activity and proinflammatory mechanisms. Thus, IPG represents a promising co-adjuvant agent in oxazaphosphorine-based chemotherapy treatments.
PubMed: 35625456
DOI: 10.3390/biology11050728 -
British Journal of Clinical Pharmacology May 1987The pharmacokinetics of mesna (sodium 2-mercaptoethane sulphonate) and its inactive disulphide, dimesna, were investigated using high performance liquid chromatography... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The pharmacokinetics of mesna (sodium 2-mercaptoethane sulphonate) and its inactive disulphide, dimesna, were investigated using high performance liquid chromatography in six normal subjects following intravenous and oral administration of 800 mg mesna. The mean maximum mesna concentration after i.v. administration was 111 (s.d. +/- 28.3) nmol ml-1 and the mean maximum dimesna concentration was 183 (s.d. +/- 41.6) nmol ml-1. Following oral mesna dosing the mean peak mesna concentration was 19.6 (s.d. +/- 10.2) nmol ml-1 but mesna was only found in the plasma of five of the six subjects. The mean peak dimesna concentration was 22.5 (s.d. +/- 12.4) nmol ml-1. Following i.v. mesna administration, the mean half-life of mesna was 21.8 (s.d. +/- 3.1) min and total body clearance 1.23 (s.d. +/- 0.31) l kg-1 h-1. The mean half-life of dimesna was 1.17 (s.d. +/- 0.32) h. It was not possible to determine their half-lives after oral mesna administration. The mean mesna concentration in the 0-4 h urine collection was 9.6 (s.d. +/- 10.7; range 1.4-28.7) nmol ml-1 following i.v. mesna injection. After oral mesna the highest mesna concentration occurred in either the 0-4 or 4-8 h urine collections. The mean peak mesna concentration was 2.5 (s.d. +/- 1.7) mumol ml-1 (c.f. estimated uroprotective concentration of 1.7 mumol ml-1). The mean 4 h urinary clearance of the uroprotective species mesna was 0.413 (s.d. +/- 0.136) l kg-1 h-1. After both i.v. and oral mesna the urinary excretion of mesna is predominantly during the first 4 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Administration, Oral; Adult; Female; Humans; Injections, Intravenous; Kinetics; Male; Mercaptoethanol; Mesna; Middle Aged
PubMed: 3109461
DOI: 10.1111/j.1365-2125.1987.tb03092.x -
Journal of the Advanced Practitioner in... Nov 2021Retroperitoneal liposarcomas (RLPS) are rare tumors that have variable clinical behavior and complex treatment strategies based on presentation, histopathology, and...
Retroperitoneal liposarcomas (RLPS) are rare tumors that have variable clinical behavior and complex treatment strategies based on presentation, histopathology, and genomics. Early identification is critical, and complete surgical resection remains the primary treatment, although chemotherapy and radiation are used on individual bases. Presenting symptoms are often nonspecific; therefore, a high degree of suspicion is essential for early diagnosis. In this report, the management of a 37-year-old otherwise healthy male with a large RLPS causing right groin/testicular pain is presented. After three evaluations in the emergency department, the patient was diagnosed and received two cycles of doxorubicin/ifosfamide/mesna (AIM) neoadjuvant chemotherapy. His physical exam on presentation for second opinion demonstrated a large palpable abdominal mass and fullness around the right spermatic cord. There was no appreciable change in tumor size or distant metastases on repeat scanning. Given some obstructive symptoms, a multidisciplinary team advised neoadjuvant radiation followed by radical resection of RLPS. Final pathology demonstrated a 31-cm grade II well-differentiated (WD) liposarcoma with low-grade dedifferentiation. Scattered foci of microscopic positive WD margins were noted, and the remainder of margins were negative. Genomic evaluation showed amplification of , and . A concise literature review of common presentations, histopathology, genomics, and treatment information is discussed herein. Thorough physical exams, attention to subtle findings, appropriate medical imaging studies, and a high index of suspicion when evaluating vague symptomatology can lead to earlier diagnosis and treatment of RLPS, and ultimately better patient outcomes.
PubMed: 35295543
DOI: 10.6004/jadpro.2021.12.8.6 -
Proceedings of the National Academy of... Sep 2022Mercaptoethane sulfonate or coenzyme M (CoM) is the smallest known organic cofactor and is most commonly associated with the methane-forming step in all methanogenic...
Mercaptoethane sulfonate or coenzyme M (CoM) is the smallest known organic cofactor and is most commonly associated with the methane-forming step in all methanogenic archaea but is also associated with the anaerobic oxidation of methane to CO in anaerobic methanotrophic archaea and the oxidation of short-chain alkanes in species. It has also been found in a small number of bacteria capable of the metabolism of small organics. Although many of the steps for CoM biosynthesis in methanogenic archaea have been elucidated, a complete pathway for the biosynthesis of CoM in archaea or bacteria has not been reported. Here, we present the complete CoM biosynthesis pathway in bacteria, revealing distinct chemical steps relative to CoM biosynthesis in methanogenic archaea. The existence of different pathways represents a profound instance of convergent evolution. The five-step pathway involves the addition of sulfite, the elimination of phosphate, decarboxylation, thiolation, and the reduction to affect the sequential conversion of phosphoenolpyruvate to CoM. The salient features of the pathway demonstrate reactivities for members of large aspartase/fumarase and pyridoxal 5'-phosphate-dependent enzyme families.
Topics: Anaerobiosis; Archaea; Bacteria; Coenzymes; Euryarchaeota; Mesna; Methane; Oxidation-Reduction; Phosphates
PubMed: 36037354
DOI: 10.1073/pnas.2207190119 -
Acta Medica Indonesiana Apr 2016We present 2 patients who developed spontaneous pneumothorax (SP) following rapid regression of lymphoma and rhabdomyosarcoma with lung metastases. Case 1, a 43-year old...
We present 2 patients who developed spontaneous pneumothorax (SP) following rapid regression of lymphoma and rhabdomyosarcoma with lung metastases. Case 1, a 43-year old man was admitted to our hospital with dyspnea 10 days before admission. He denied any recent trauma or previous treatment for lung tuberculosis. Three weeks prior to admission, he received first cycle of CHOP for non-Hodgkin's lymphoma stage II BE. Chest X-ray consistent with right pneumothorax. After treatment with chest tube drainage for about 1 month, the patient recovered and chemotherapy could be continued without further complications. Case 2, a 35- year old man was admitted to other hospital with dyspnea and chest pain on day 4 after second cycle of systemic combined chemotherapy for rhabdomyosarcoma stage IV (lung metastases) with doxorubicin, ifosfamide, mesna, and dacarbazine. Chest X-ray showed hydropneumothorax on right and left lung. After treatment with chest tube drainage about 2 weeks, the patient recovered and chemotherapy could be continued without further complications. The mechanism of pneumothorax following chemotherapy is not clearly understood yet, however, several hypotheses have been considered: 1) the rupture of a subpleural bulla after chemotherapy; 2) the rupture of an emphysematous bulla in an over expanded portion of the lung which is partially obstructed by a neoplasm; 3) tumor lyses or necrosis due to cytotoxic chemotherapy directly induces the formation of fistula. Dyspnea and chest pain suddenly appear during successful chemotherapy for metastatic chemosensitive tumors should alert the physician to the possibility of SP. The treatment is directed toward lung re-expansion. Chemotherapy induced pneumothorax should be considered as oncologic emergency.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chest Pain; Drainage; Humans; Lung Neoplasms; Lymphoma, Non-Hodgkin; Male; Pneumothorax; Radiography, Thoracic; Tomography, X-Ray Computed
PubMed: 27550883
DOI: No ID Found -
Transplantation and Cellular Therapy Jul 2022Post-transplantation cyclophosphamide (PTCy) has improved hematopoietic stem cell transplantation outcomes for patients with major HLA disparities. Although PTCy in... (Review)
Review
A Clinical Review of the Different Strategies to Minimize Hemorrhagic Cystitis Associated with the Use of Post-Transplantation Cyclophosphamide in an Allogeneic Transplant.
Post-transplantation cyclophosphamide (PTCy) has improved hematopoietic stem cell transplantation outcomes for patients with major HLA disparities. Although PTCy in combination with calcineurin inhibitors is a successful graft-versus-host disease regimen, giving high doses of cyclophosphamide may cause hemorrhagic cystitis (HC). The strategies used to prevent HC are adapted from published data in the pre-transplantation conditioning setting. However, there is no consensus on what the optimal strategy is to prevent PTCy-associated HC. This review provides a summary of the different preventative strategies used in this setting. Based on the results published in current literature, hyperhydration is an effective preventative strategy, but it may cause fluid overload and other complications. Additionally, mesna at least 100% of the PTCy dose should be administered as a continuous infusion or frequent intermittent bolus infusion. More comparative studies between these strategies are needed to provide a definitive solution for preventing HC associated with PTCy.
Topics: Cyclophosphamide; Cystitis; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hemorrhage; Humans; Transplantation, Homologous
PubMed: 35580733
DOI: 10.1016/j.jtct.2022.05.012 -
Indian Journal of Cancer 2006Hemorrhagic cystitis (HC) is a dose limiting side effect of cyclophosphamide (CYP).
BACKGROUND
Hemorrhagic cystitis (HC) is a dose limiting side effect of cyclophosphamide (CYP).
AIM
In this study, we aimed to investigate the role of amifostine in the protection of CYP-induced HC and compare its efficacy with mesna.
SETTING AND DESIGN
This animal study was conducted in the Experimental Animals Breeding and Research Center of the Medical Faculty of Uludag University.
MATERIALS AND METHODS
Male Wistar rats (150-200 g; 10 rats per group) were randomly assigned to four groups. Group I (control group) received no drugs, group II received CYP (200 mg/kg, i.p.) alone, group III received amifostine (200 mg/kg, i.p.) and CYP, and group IV received CYP and mesna (40 mg/kg, i.p.) immediately and 4 and 8 h after administration of CYP. Bladders of animals were assessed macroscopically and histologically 24 h later. Gross assessment for presence of edema and hemorrhage and histological evaluation of damage to the bladder were scored according to Gray's criteria.
STATISTICAL ANALYSIS USED
For macroscopic and microscopic data, we used statistical evaluation by Kruskal-Wallis nonparametric analysis of variance followed by the Mann-Whitney U-test.
RESULTS
All the animals in group II had evidence of HC. Significant histological damage and macroscopic changes were present in this group compared to control group (P<0.001). The median scores for bladder damage in group III and IV were significantly lower compared to group II (P<0.001). When the median scores for bladder damage of group I, III, and IV were compared, there was no significant difference among these groups.
CONCLUSION
This study demonstrated the efficacy of amifostine in prevention of cyclophosphamide-induced hemorrhagic cystitis.
Topics: Amifostine; Animals; Cyclophosphamide; Cystitis; Hemorrhage; Male; Mesna; Mutagens; Radiation-Protective Agents; Rats; Rats, Wistar; Urinary Bladder
PubMed: 16763356
DOI: 10.4103/0019-509x.25769 -
Romanian Journal of Morphology and... 2006Retroperitoneal synovial sarcomas are very rare. The authors describe a 39-year-old male with a primary retroperitoneal synovial sarcoma showing a monophasic pattern....
Retroperitoneal synovial sarcomas are very rare. The authors describe a 39-year-old male with a primary retroperitoneal synovial sarcoma showing a monophasic pattern. Immunohistochemically, the tumor cells were positive for cytokeratin AE1/AE3, epithelial membrane antigen, vimentin, S-100 protein, CD99 and calretinin. The differential diagnosis, clinical evolution and principles of treatment are shortly discussed.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Dacarbazine; Doxorubicin; Humans; Ifosfamide; Male; Mast Cells; Mesna; Mitosis; Retroperitoneal Neoplasms; Sarcoma, Synovial; Thoracic Neoplasms
PubMed: 17106529
DOI: No ID Found -
Journal of Medicinal Chemistry Dec 2021Commonly used non-antibiotic drugs have been associated with changes in gut microbiome composition, paving the way for the possibility of repurposing FDA-approved...
Commonly used non-antibiotic drugs have been associated with changes in gut microbiome composition, paving the way for the possibility of repurposing FDA-approved molecules as next-generation microbiome therapeutics. Herein, we developed and validated an high-throughput screening platform─the mini gut model─to underpin human gut microbiome response to molecular modulators. Ten FDA-approved compounds, selected based on maximum structural diversity of molecular fingerprints, were screened against the gut microbiome of five healthy subjects to characterize the ability of human-targeted drugs to modulate the human gut microbiome network. Three compounds, THIP hydrochloride, methenamine, and mesna, have shown promise as novel gut microbiome therapeutics in light of their capability of promoting health-associated features of the gut microbiome. Our findings provide a resource for future research on drug-microbiome interactions and lay the foundation for a new era of more precise gut microbiome modulation through drug repurposing, aimed at targeting specific dysbiotic events.
Topics: Drug Repositioning; Gastrointestinal Microbiome; Gene Expression Profiling; High-Throughput Screening Assays; Humans; Validation Studies as Topic
PubMed: 34846885
DOI: 10.1021/acs.jmedchem.1c01333 -
Annals of Oncology : Official Journal... Apr 1992While significant improvements have been made in the management of localized soft tissue sarcomas, enabling the realization of better functional results and a better... (Review)
Review
While significant improvements have been made in the management of localized soft tissue sarcomas, enabling the realization of better functional results and a better overall outcome, progress in metastatic disease has been less than impressive. Adriamycin and DTIC based chemotherapy programs have resulted in response rates of upto 50%, with a small but finite cure fraction, especially in conjunction with surgical resection of residual abnormalities. The decade of the 80s experienced a considerable amount of enthusiasm in exploring the role of ifosfamide and mesna, and identified its definite usefulness as an effective salvage regimen with response rates of approximately 25%-30% in adriamycin failures. Studies evaluating the role of ifosfamide as up-front line agent in combination with adriamycin have met with increased toxicities without a significant additive therapeutic benefit, probably as a result of compromised dose intensity of each individual agent. The steep linear log-dose response relationship of alkylating agents and adriamycin constitutes the theoretical rationale for use of higher doses of chemotherapy, which have become feasible, with the advent of growth factors for bone marrow support. While this approach seems promising in its infancy, with improved complete and overall response, its ultimate effect on survival is anxiously awaited. The limited experience available in the literature with even more aggressive approaches like marrow ablative doses of chemotherapy followed by bone marrow transplantation, have been uniformly disappointing, with extremely short lived responses and extremely high morbidity and cost. As clinical research continues to improve our understanding and ability to implement the currently available therapeutic armamentarium, the search for newer and better drugs needs to continue.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Antineoplastic Agents; Dose-Response Relationship, Drug; Humans; Sarcoma; Soft Tissue Neoplasms
PubMed: 1622875
DOI: 10.1093/annonc/3.suppl_2.s81