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Nigerian Journal of Clinical Practice Jul 2023Ischemia-reperfusion (I/R) causes organ dysfunction as a result of the increased formation of various reactive oxygen metabolites, infiltration of inflammatory cells,...
BACKGROUND
Ischemia-reperfusion (I/R) causes organ dysfunction as a result of the increased formation of various reactive oxygen metabolites, infiltration of inflammatory cells, interstitial edema, cellular dysfunction, and tissue death.
AIM
The study aimed to investigate the cytoprotective effect of 2-mercaptoethanesulfonate (MESNA) against tissue damage in rats exposed to carotid ischemia-reperfusion.
MATERIALS AND METHODS
Twenty-four male Wistar albino rats were divided into four groups (n = 6): sham, carotid I/R, I/R + MESNA (75 mg/kg), and I/R + MESNA (150 mg/kg) groups. To induce ischemia in rats, the carotid arteries were ligated with silk sutures for 10 min; the silk suture was then opened, and 1 h reperfusion was done. MESNA (75 and 150 mg/kg) was administered intraperitoneally 30 min before ischemia-reperfusion. Tissue samples from the animals were taken for histological examination, while the serum levels of some biochemical parameters were utilized to evaluate the systemic alterations. ANOVA and Tukey's post hoc tests were applied with a significance level of 5%.
RESULTS
The ischemia-reperfusion-induced tissue damage as evidenced by increase in serum levels of alanine transaminase, aspartate aminotransferase, alkaline phosphatase, malondialdehyde, lactate dehydrogenase, and matrix metalloproteinases (MMP-1, -2, -8) was significantly (P < 0.05-0.0001) reversed after treatment with MESNA in a dose-dependent manner. Treatment with MESNA (75 and 150 mg/kg), significantly (P < 0.05-0.0001) decreased the I/R-induced increase in serum tumor necrosis factor-alpha (TNF-α) and Interleukin-1-beta (IL-1 β).
CONCLUSION
The results of this study suggest that MESNA has a protective effect on tissues by suppressing cellular responses to oxidants and inflammatory mediators associated with carotid ischemia-reperfusion.
Topics: Male; Rats; Animals; Mesna; Lung Injury; Rats, Wistar; Brain; Ischemia; Reperfusion; Silk
PubMed: 37635578
DOI: 10.4103/njcp.njcp_654_22 -
ACS Omega Feb 2024This study aimed at designing an S-protected thiolated β-cyclodextrin (β-CD) exhibiting enhanced mucoadhesive properties. The native β-CD was thiolated with...
This study aimed at designing an S-protected thiolated β-cyclodextrin (β-CD) exhibiting enhanced mucoadhesive properties. The native β-CD was thiolated with phosphorus pentasulfide resulting in a thiolated β-CD (β-CD-SH) and subsequently S-protected with 2-mercaptoethanesulfonate (MESNA) to form β-CD-SS-MESNA. The structure of the novel excipient was confirmed by H NMR and Fourier-transform infrared spectroscopy. The sulfhydryl content of β-CD-SH, determined by Ellman's test, was 2281.00 ± 147 μmol/g, and it was decreased to 45.93 ± 19.40 μmol/g by S-protection. Due to thiolation and S-protection, the viscosity of the mixture of mucus with β-CD-SH and β-CD-SS-MESNA increased 1.8 and 4.1-fold, compared to native β-CD, respectively. The unprotected β-CD-SH diffused to a lesser extent into the mucus than native β-CD, while S-protected β-CD-SS-MESNA showed the highest mucodiffusion among the applied CDs. A 1.5- and 3.0-fold higher cellular uptake of β-CD-SH and β-CD-SS-MESNA, compared to the native one, was established on Caco-2 cell line by flow cytometry, respectively, causing slightly decreased cell viability. On account of the enhanced mucoadhesion, this higher cellular uptake does not affect the application potential of β-CD-SS-MESNA as an oral drug delivery system since the carrier remains in the mucus and does not reach the underlying epithelial layer. According to these results, the S-protection of β-CD-SH with MESNA promotes improved mucodiffusion, strong mucoadhesion, and prolonged mucosal residence time.
PubMed: 38343993
DOI: 10.1021/acsomega.3c08836 -
Otolaryngologia Polska = the Polish... Jul 2023<b>Introduction:</b> Surgery is still the method of choice in chronic otitis media with cholesteatoma. Except for some specific clinical situations, classic...
<b>Introduction:</b> Surgery is still the method of choice in chronic otitis media with cholesteatoma. Except for some specific clinical situations, classic canal wall up technique (CWU), remains a gold standard as a primary treatment in most departments. Unfortunately, the risk of recurrence in such an approach is estimated at 9 to even 70%. This fact prompts researchers to look for ways to reduce those unfavourable statistics. One of the recognized methods supporting the removal of cholesteatoma is the intraoperative use of mesna (sodium 2-mercaptoethanesulfonate). This synthetic sulphur compound disrupts disulfide bridges in polypeptide chains, thanks to which it facilitates matrix preparation.</br></br> <b>Aim:</b> To evaluate the effect of intraoperative use of mesna on the treatment outcomes in patients with chronic otitis media with cholesteatoma operated on by means of the canal wall up technique (CWU).</br></br> <b>Material and methods:</b> 459 surgical reports of patients with middle ear cholesteatoma were analyzed. In total, 52 adult patients with no history of previous ear surgery operated on by means of the CWU technique by the same experienced otosurgeon with all follow-up data available were included in the study. Twenty-six were operated on with the use of mesna (mesna group) and 26 by means of the classic CWU technique (control / no-mesna group). There were 28 women and 24 men with a mean age of 41 years.</br></br> <b>Main Outcome Measure(s):</b> Postoperative hearing results and cholesteatoma recidivism rate.</br></br> <b>Results:</b> Overall recidivism rate was 21.15 %. It was higher in the no-mesna (26.9%) than in the mesna group (15.4%) - although the outcomes were better in the mesna group, the difference was not statistically significant (P = 0.49715). Hearing gain was better in the mesna than in the no-mesna group (10 dB vs 7 dB), but the difference was not statistically significant (P = 0.20089).</br></br> <b>Conclusions:</b> Our preliminary results show that mesna reduces recidivism rates in patients with cholesteatoma. Further study with the analysis of a larger group of patients is needed to prove it statistically.
PubMed: 37772375
DOI: 10.5604/01.3001.0016.3415 -
Cureus Feb 2024Polyarteritis nodosa (PAN) is a connective tissue disease that affects arteries, causing necrotizing inflammation that can weaken the arterial walls, dilatation into...
Polyarteritis nodosa (PAN) is a connective tissue disease that affects arteries, causing necrotizing inflammation that can weaken the arterial walls, dilatation into aneurysms, and rupture in some cases. We present a case of a male with acute abdomen from aneurysmal rupture. The 48-year-old patient with a history of polysubstance use including cocaine and methamphetamines was admitted for acute hypoxic respiratory failure secondary to coronavirus disease 2019 (COVID-19) pneumonia and treated with broad-spectrum antibiotics and steroids. He also reported generalized abdominal pain and discomfort, and examination revealed abdominal distension that was diffusely tender on palpation, bowel sounds intact. Laboratory workup showed a progressive drop in hemoglobin requiring blood transfusions, no coagulopathy, anion gap metabolic acidosis, and lactic acidosis. Abdominal CT showed a 2 cm lobulated saccular aneurysm involving either the left gastric artery or splenic artery, associated with an extensive moderate amount of hemoperitoneum with hematomas (largest measuring up to 8.6 cm) abutting the gastric fundus and greater curvature of the stomach, which was likely secondary to aneurysmal rupture. Additionally, several other mesenteric vessels displayed some degree of dilation. Interventional radiology (IR)-guided splenic artery embolization for splenic artery aneurysm was done, after which his hemoglobin remained stable. The patient was given vaccine recommendations since splenic artery embolization would lead to asplenia. The aneurysms were attributed to either cocaine-related aneurysms or polyarteritis nodosa with visceral artery aneurysms. He denied rashes, oral ulcers, joint pain, subcutaneous nodules, blood in the urine, history of hepatitis or syphilis. Tertiary syphilis was ruled out after the Venereal Disease Research Laboratory (VDRL) test and rapid plasma reagin (RPR) test were negative. Complement C3 and C4 levels were normal. He was treated with high-dose IV methylprednisone after infection was ruled out. Due to the severity of PAN, therapy with IV cyclophosphamide therapy 15 mg/kg once every two weeks for three doses was initiated, followed by 15 mg/kg once every three weeks for three to six months (in combination with glucocorticoids prednisone 1 mg/kg body weight with slow taper). Cyclophosphamide was given with IV hydration and mesna. The presentation of PAN can vary widely. Most commonly, individuals experience symptoms such as fatigue, weight loss, fever, and chills. However, in rare cases, patients may present with isolated abdominal pain, similar to our patient. It's crucial to note that the rupture of an aneurysm can manifest as an acute abdominal issue, potentially leading to life-threatening situations. Immediate interventions to control bleeding are imperative in such cases. The treatment of PAN has a high success rate when a combination of cyclophosphamide and steroids is administered.
PubMed: 38558645
DOI: 10.7759/cureus.55143 -
Journal of Osteopathic Medicine Mar 2024An important diagnostic tool, ultrasound (US) has been incorporated into the curriculum of medical schools for more than 20 years. In the last decade, the interest in...
CONTEXT
An important diagnostic tool, ultrasound (US) has been incorporated into the curriculum of medical schools for more than 20 years. In the last decade, the interest in US educational research has experienced exponential growth but mostly from Medical Doctor (MD)-granted schools. The extent to which US is embedded in the curricula of the colleges of osteopathic medicine (COM) still requires a comprehensive evaluation.
OBJECTIVES
This survey is designed to evaluate the current status of US teaching in COMs with an emphasis on the inclusion of the US in osteopathic manipulative medicine (OMM) training.
METHODS
An anonymous, voluntary, 22-question online survey was created and administered to all COMs to collect data about the current state of US teaching. A descriptive analysis was performed to describe and summarize the final data. Fisher's exact test was utilized for the comparison of study variables.
RESULTS
We received responses from 36 of the 43 (83.7 %) COMs invited to participate in the survey, all of which had US training within their curriculum, most commonly integrated into the year 1 curriculum (86.1 %). Focused US training is incorporated into 83.3 % of these schools (30 of 36). Focused US training is covered in 83.3 % of schools (30 of 36). US is mostly taught in the anatomy course (38.8 %). US is incorporated in the OMM course in 12 of 36 schools (33.3 %). The majority of respondents feel that US training will make osteopathic students more competitive in the job market (88.9 %) and want more US in their curriculum (86.1 %). The idea that US is useful for a better understanding of the key OMM concepts is believed by 62.9 % of respondents. The major obstacle to the implementation of US in the curriculum is having appropriately trained faculty (86.1 %). The majority of the respondents did not feel that an adequate budget is a handicap to implementing US in the curriculum.
CONCLUSIONS
US is included within the curriculum of all respondents to our survey, a third of whom included US within their OMM curriculum. US is treated as a useful and important skill for future osteopathic physicians. The majority of COMs desire more US training in the curriculum. The main barrier to implementing US in the curriculum is the lack of appropriately trained faculty.
Topics: Humans; Schools, Medical; Curriculum; Emotions; Manipulation, Osteopathic; Mesna
PubMed: 38053432
DOI: 10.1515/jom-2023-0027 -
JCEM Case Reports Sep 2023Primary pituitary T-lymphoblastic lymphoma is a rare clinical entity. A 45-year-old woman presented with headache, left-eye blurry vision, diplopia, ophthalmoplegia, and...
Primary pituitary T-lymphoblastic lymphoma is a rare clinical entity. A 45-year-old woman presented with headache, left-eye blurry vision, diplopia, ophthalmoplegia, and ptosis. Magnetic resonance imaging of the brain showed a sellar mass most likely consistent with a pituitary macroadenoma. Laboratory evaluation disclosed secondary hypothyroidism, secondary adrenal insufficiency, and hyperprolactinemia. The mass was removed by transsphenoidal resection, and subsequent immunophenotyping revealed T-cell lymphoblastic lymphoma. Secondary workup confirmed lymphomatous confinement to the central nervous system. Following resection, the patient's headaches improved, but she experienced persistent visual deficits and palsies of cranial nerves III, IV, and VI. The chemotherapy regimen consisted of high-dose methotrexate, followed by alternating cycles of cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride (Adriamycin), dexamethasone (cyclophosphamide, mesna, vincristine sulfate, doxorubicin hydrochloride, dexamethasone), and methotrexate/cytarabine. Since receiving chemotherapy, there has been an improvement in numbness, ptosis, left orbital pressure, and headaches. This case represents only the eighth example of T-cell primary pituitary lymphoma, and the youngest patient to receive the diagnosis.
PubMed: 37908217
DOI: 10.1210/jcemcr/luad097 -
Scientific Reports Jul 2023Electrochemical impedance spectroscopy (EIS) is a highly effective technique for studying the surface of electrodes in great detail. EIS-based electrochemical sensors...
Electrochemical impedance spectroscopy (EIS) is a highly effective technique for studying the surface of electrodes in great detail. EIS-based electrochemical sensors have been widely reported, which measure the charge transfer resistance (R) of redox probes on electrode surfaces to monitor the binding of target molecules. One of the protective drugs against hemorrhagic cystitis caused by oxazaphosphorine chemotherapy drugs such as ifosfamide, cyclophosphamide and trophosphamide is Mesna (sodium salt of 2-mercaptoethanesulfonate). The increase in the use of Mesna due to the high consumption of anti-cancer drugs, the determination of this drug in biological samples is of particular importance. So far, no electrochemical method has been reported to measure Mesna. In this research, a novel impedimetric sensor based on a glassy carbon electrode (GCE) modified with oxidized multiwalled carbon nanotubes (MWCNTs)/gold nanoparticle (AuNPs) (denoted as Au NPs/MWCNTs/GCE) for impedimetric determination of Mesna anticancer drug was developed. The modified electrode materials were characterized by field emission scanning electron microscopy (FESEM), energy dispersive X-ray (EDX), and EIS. The electrochemical behavior of Mesna at the surface of Au NPs/MWCNTs/GCE was studied by an impedimetric method. The detection mechanism of Mesna using the proposed impedimetric sensor relied on the increase in the R value of [Fe (CN)] as an electrochemical probe in the presence of Mesna compared to the absence of Mesna as the analyte. Under the optimum condition, which covered two linear dynamic ranges from 0.06 nmol L to 1.0 nmol L and 1.0 nmol L to 130.0 µmol L, respectively. The detection limit was 0.02 nmol L. Finally, the performance of the proposed sensor was investigated for Mesna electrochemical detection in biological samples.
Topics: Metal Nanoparticles; Mesna; Gold; Nanotubes, Carbon; Antineoplastic Agents; Electrodes; Electrochemical Techniques; Limit of Detection
PubMed: 37452101
DOI: 10.1038/s41598-023-38643-3 -
World Journal of Clinical Cases Jul 2023Angiosarcoma (AS) is a rare and highly aggressive soft tissue disease that most commonly arises in deep soft tissues. There are only a few reported cases of AS involving...
BACKGROUND
Angiosarcoma (AS) is a rare and highly aggressive soft tissue disease that most commonly arises in deep soft tissues. There are only a few reported cases of AS involving the ovary and even fewer reports of the underlying molecular abnormalities. Here, we briefly review two cases of primary ovarian AS (oAS) with specific molecular events and immune checkpoints. The clinical features and prognosis of the disease, diagnosis, differential diagnosis, and new treatment approaches are discussed based on a literature review.
CASE SUMMARY
Case 1: A 51-year-old female patient was admitted with right lower limb pain for 5 mo, and lower abdominal pain with hematuria for 1 mo. Partial removal of rectus abdominis muscle and fascia, partial hysterectomy, bilateral salpingo-oophorectomy, and inguinal and pelvic lymphadenectomy were performed. Pathology revealed primary oAS. Fluorescence hybridization revealed gene amplification. MESNA + ADM + IFO + DTIC (MAID) regimen was administered, but stable disease was achieved. The patient died 1 mo later. Case 2: A 41-year-old female patient presented with fatigue, nausea, decreased appetite, and diffuse abdominal pain. On physical examination, the abdomen was distended and a complex cystic mass was palpable in the right pelvic cavity. Pathology revealed primary oAS. MAID chemotherapy was administered and programmed death ligand 1 (PD-L1) staining was performed on the tumor samples. The patient benefited from anti-PD-1 immunotherapy and is alive without any evidence of disease 27 mo off therapy in follow-up.
CONCLUSION
Long-term survival benefit for primary oAS can be achieved by alternative therapeutic strategies using pathological indicators to inform treatment.
PubMed: 37583851
DOI: 10.12998/wjcc.v11.i21.5122 -
International Journal of Pharmaceutics May 2024This study aims to design chemically crosslinked thiolated cyclodextrin-based hydrogels and to evaluate their mucoadhesive properties via mucosal residence time studies...
AIM
This study aims to design chemically crosslinked thiolated cyclodextrin-based hydrogels and to evaluate their mucoadhesive properties via mucosal residence time studies on porcine small intestinal mucosa and on porcine buccal mucosa.
METHODS
Free thiol groups of heptakis(6-deoxy-6-thio)-β-cyclodextrin (β-CD-SH) were S-protected with 2-mercaptoethanesulfonic acid (MESNA) followed by crosslinking with citric acid. Cytotoxicity was assessed by hemolysis as well as resazurin assay. Hydrogels were characterized by their rheological and mucoadhesive properties. Ritonavir was employed as model drug for in vitro release studies from these hydrogels.
RESULTS
The structure of S-protected β-CD-SH was confirmed by IR and H NMR spectroscopy. Degree of thiolation was 390 ± 7 µmol/g. Hydrogels based on native β-CD showed hemolysis of 12.5 ± 2.5 % and 13.6 ± 2.7 % within 1 and 3 h, whereas hemolysis of just 3.5 ± 2.8 % and 3.9 ± 3.0 % was observed for the S-protected thiolated CD hydrogels, respectively. Both native and S-protected thiolated hydrogels showed minor cytotoxicity on Caco-2 cells. Rheological investigations of S-protected thiolated β-CD-based hydrogel (16.2 % m/v) showed an up to 13-fold increase in viscosity in contrast to the corresponding native β-CD-based hydrogel. Mucosal residence time studies showed that thiolated β-CD-based hydrogel is removed to a 16.6- and 2.4-fold lower extent from porcine small intestinal mucosa and porcine buccal mucosa in comparision to the native β-CD-based hydrogel, respectively. Furthermore, a sustained release of ritonavir from S-protected thiolated β-CD-based hydrogels was observed.
CONCLUSION
Because of their comparatively high mucoadhesive and release-controlling properties, S-protected thiolated β-CD-based hydrogels might be promising systems for mucosal drug delivery.
Topics: Hydrogels; Animals; Humans; Caco-2 Cells; Swine; Sulfhydryl Compounds; Mouth Mucosa; beta-Cyclodextrins; Intestinal Mucosa; Rheology; Hemolysis; Adhesiveness; Drug Liberation; Polymers; Cell Survival; Intestine, Small
PubMed: 38599445
DOI: 10.1016/j.ijpharm.2024.124075