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Nature Communications Oct 2022Soil viruses remain understudied when compared to virus found in aquatic ecosystems. Here, we investigate the ecological patterns of soil viral communities across...
Soil viruses remain understudied when compared to virus found in aquatic ecosystems. Here, we investigate the ecological patterns of soil viral communities across various land use types encompassing forest, agricultural, and urban soil in Xiamen, China. We recovered 59,626 viral operational taxonomic units (vOTUs) via size-fractioned viromic approach with additional mitomycin C treatment to induce virus release from bacterial fraction. Our results show that viral communities are significantly different amongst the land use types considered. A microdiversity analysis indicates that selection act on soil vOTUs, resulting in disparities between land use associated viral communities. Soil pH is one of the major determinants of viral community structure, associated with changes of in-silico predicted host compositions of soil vOTUs. Habitat disturbance and variation of soil moisture potentially contribute to the dynamics of putative lysogenic vOTUs. These findings provide mechanistic understandings of the ecology and evolution of soil viral communities in changing environments.
Topics: Agriculture; Ecosystem; Mitomycin; Soil; Soil Microbiology
PubMed: 36224209
DOI: 10.1038/s41467-022-33771-2 -
Proteins Jul 2011Mitomycins are quinone-containing antibiotics, widely used as antitumor drugs in chemotherapy. Mitomycin-7-O-methyltransferase (MmcR), a key tailoring enzyme involved in...
Mitomycins are quinone-containing antibiotics, widely used as antitumor drugs in chemotherapy. Mitomycin-7-O-methyltransferase (MmcR), a key tailoring enzyme involved in the biosynthesis of mitomycin in Streptomyces lavendulae, catalyzes the 7-O-methylation of both C9β- and C9α-configured 7-hydroxymitomycins. We have determined the crystal structures of the MmcR-S-adenosylhomocysteine (SAH) binary complex and MmcR-SAH-mitomycin A (MMA) ternary complex at resolutions of 1.9and 2.3 Å, respectively. The study revealed MmcR to adopt a common S-adenosyl-L-methionine-dependent O-methyltransferase fold and the presence of a structurally conserved active site general acid-base pair is consistent with a proton-assisted methyltransfer common to most methyltransferases. Given the importance of C7 alkylation to modulate mitomycin redox potential, this study may also present a template toward the future engineering of catalysts to generate uniquely bioactive mitomycins.
Topics: Amino Acid Sequence; Bacterial Proteins; Binding Sites; Crystallography, X-Ray; Methyltransferases; Mitomycin; Models, Molecular; Molecular Sequence Data; Protein Binding; Protein Folding; Protein Structure, Tertiary; Recombinant Proteins; S-Adenosylhomocysteine; Sequence Alignment; Streptomyces; Structural Homology, Protein
PubMed: 21538548
DOI: 10.1002/prot.23040 -
Microbiology Spectrum Dec 2022Here, we performed susceptibility testing on 10 Mycoplasma genitalium isolates against omadacycline, minocycline, tetracycline, doxycycline, moxifloxacin, levofloxacin,...
Here, we performed susceptibility testing on 10 Mycoplasma genitalium isolates against omadacycline, minocycline, tetracycline, doxycycline, moxifloxacin, levofloxacin, and azithromycin. Omadacycline was the most potent agent, with all MICs of ≤0.5 μg/mL. MICs were not affected by resistance to other agents, including resistance to other tetracycline class drugs. Omadacycline may be a potential treatment option for M. genitalium infection. There are very few clinical isolates of Mycoplasma genitalium available for susceptibility testing. We studied 10 isolates and determined that the new semisynthetic aminomethylcycline omadacycline is active against isolates that are resistant to tetracyclines, macrolides, and quinolones. These data suggest that clinical studies should be performed in order to see if omadacycline may be useful to treat urogenital infections caused by M. genitalium.
Topics: Humans; Tetracycline; Mycoplasma genitalium; Mycoplasma Infections; Drug Resistance, Bacterial; Anti-Bacterial Agents; Macrolides; Quinolones; Minocycline; Mitomycin; Protein Synthesis Inhibitors
PubMed: 36314935
DOI: 10.1128/spectrum.03654-22 -
Indian Journal of Ophthalmology Apr 2020To determine the safety and efficacy of mitomycin C (MMC) injection versus sponge during trabeculectomy.
PURPOSE
To determine the safety and efficacy of mitomycin C (MMC) injection versus sponge during trabeculectomy.
METHODS
It is a prospective analysis of patients who underwent trabeculectomy with MMC and followed up for 1 year, divided into two groups, namely, group 1- injection (n = 21), group 2-> sponge (n = 21). The same concentration of MMC was used for both groups. Inclusion criteria were trabeculectomies with MMC for intraocular pressure (IOP) control in eyes with glaucoma (primary + secondary) with a follow-up of 1 year.
RESULTS
Mean preoperative IOP in group 1 was 29.00 ± 11.92 mmHg and group 2 was 25.87 ± 11.09 mmHg, which reduced to 12.19 ± 4.03 and 15.56 ± 10.72 mmHg at final visit with P value of 0.0002 and 0.001, respectively. Mean preoperative number of antiglaucoma medications was 2.4 ± 0.87 in group 1 and 2.3 ± 0.96 in group 2, which reduced to 0.38 ± 0.5 and 0.91 ± 0.85 with P value of 0.001 and 0.0003, respectively. The complete success rate was 52.4% in the injection group and 26.1% in the sponge group at end of 1 year. Overall, success rate (complete + qualified) was 90.5% and 87% in group 1 and group 2 at final visit. All major complications were encountered in sponge group. 1 (11.1%) patient developed choroidal detachment and one had malignant glaucoma which got resolved by medical management. 33.3% cases had encapsulated bleb which received bleb needling. 44.4% cases underwent Argon laser suture lysis postoperatively.
CONCLUSION
The MMC injection may be as safe and as effective as conventional sponge application with comparable estimated complete treatment success.
Topics: Follow-Up Studies; Humans; Intraocular Pressure; Mitomycin; Prospective Studies; Trabeculectomy; Treatment Outcome
PubMed: 32174581
DOI: 10.4103/ijo.IJO_963_19 -
Respiration; International Review of... 2010An 84-year-old man with no evidence of pre-existing interstitial pneumonia developed fatal interstitial pneumonia and respiratory failure that could only be explained as...
An 84-year-old man with no evidence of pre-existing interstitial pneumonia developed fatal interstitial pneumonia and respiratory failure that could only be explained as an adverse effect of intravesical mitomycin C chemotherapy. He had undergone transurethral resection of bladder cancer 3 times, followed by intravesical mitomycin C chemotherapy 1 month later. He had received intravesical mitomycin C chemotherapy every week for 2 months, and he had complained of dyspnea on exertion 5 days before the last intravesical mitomycin C chemotherapy session. Interstitial infiltration was detected in both the upper and lower lobes of the left lung on the day of the last instillation of mitomycin C. Despite discontinuation of mitomycin C and administration of methylprednisolone, his condition deteriorated and he died. Diagnostic evaluation of other causes of pneumonia, including infection and collagen-vascular diseases, was negative. The autopsy demonstrated diffuse alveolar damage in the lung; there were no remarkable findings in other organs. To our knowledge, this is the first pathologically confirmed case of fatal interstitial pneumonia due to intravesical mitomycin C chemotherapy.
Topics: Administration, Intravesical; Aged, 80 and over; Antibiotics, Antineoplastic; Carcinoma in Situ; Fatal Outcome; Humans; Lung Diseases, Interstitial; Male; Mitomycin; Urinary Bladder Neoplasms
PubMed: 20130385
DOI: 10.1159/000280383 -
Medicine Jun 2019To evaluate the efficacy and safety of trabeculectomy (Trab) with mitomycin-C (MMC) versus Trab with implant. (Meta-Analysis)
Meta-Analysis
AIM
To evaluate the efficacy and safety of trabeculectomy (Trab) with mitomycin-C (MMC) versus Trab with implant.
METHODS
Studies published in different languages were retrieved by systematically searching Embase, PubMed, Cochrane library, China Biology Medicine disc, and Google Scholar from 1966 to April 2018, as well as manually examining the references of the original articles. The outcome measures of efficacy covered intraocular pressure, glaucoma medications reductions, and success rate. Safety evaluation was measured by relative ratio of complications.
RESULTS
A total of 11 studies involving 443 participants were covered in this meta-analysis. The weighted mean difference (WMD) in the percentage of intraocular pressure (IOP) reduction (IOPR%) comparing Ologen group with MMC group was -3.69 (95% CI: -6.70 to -0.68) at 1 month, -2.69 (-5.17 to -0.21) at 3 months, -3.67 (-6.09 to -1.25)at 6 months, -3.24 (-6.08 to -0.41) at 12 months, 1.24 (-9.43 to 11.90) at 24 months, and 1.10 (-10.11 to 12.31) at 60 months, which showed that there was statistically significant difference at 1,3, 6, and12 months after the surgery. A significantly higher incidence of postsurgery hypotony (0.64 (95% Cl: 0.42 to 0.98)) and suture lysis (0.30 (95% CI: 0.10-0.93)) was observed in MMC group. However, there was no significant difference in the reduction in glaucoma medications, success rate, and incidence of other complications.Trab with 0.2 mg/mL MMC presented higher rates of complete success compared with Trab with 0.4 mg/mL MMC (P = .01).
CONCLUSION
Trab with MMC was associated with a higher IOP-lowering efficacy and a higher incidence of postsurgery hypotony and suture lysis in contrast to that of Trab with Ologen.
Topics: Collagen; Glycosaminoglycans; Humans; Mitomycin; Prostheses and Implants; Trabeculectomy
PubMed: 31232951
DOI: 10.1097/MD.0000000000016094 -
Indian Journal of Ophthalmology Feb 2023The introduction of mitomycin C (MMC) as an adjunct to trabeculectomy was a major advance in the ability to improve the Intra ocular pressure lowering efficiency of the...
BACKGROUND
The introduction of mitomycin C (MMC) as an adjunct to trabeculectomy was a major advance in the ability to improve the Intra ocular pressure lowering efficiency of the procedure. The time tested traditional way of administration of MMC is via a sponges soaked in it, duration and concentration varies depending on risk of failure. A subconjunctival injection of MMC instead of these sponges is recently being used as a promising alternative.
PURPOSE
Here is the video demonstrating the 2 possible ways to prepare and apply MMC during a trabeculectomy surgery.
SYNOPSIS
Intraoperative injection of MMC in trabeculectomy has several advantages over conventional method ofsponge application. A large MMC treatment area produces more diffuse and elevated blebs. Large-area MMC application also seems to increase long-term success without increasing the complication rates in trabeculectomies. Direct and diffuse application of MMC by injection may promote less scarring and vascularization of the bleb. To achieve the same surface area of exposure with sponges, i.e.achieved with injection, the surgeon must use multiple sponges, all of which must be carefully collected thereafter. The injection method,therefore,eliminates the risk of retained sponges.
HIGHLIGHTS
injection of MMC may be as safe and as effective as conventional sponge application of MMC with comparable estimated complete treatment success with relatively lower complication rates.
VIDEO LINK
https://youtu.be/RLEbK4IeRtU.
Topics: Humans; Mitomycin; Trabeculectomy; Intraocular Pressure; Treatment Outcome; Tonometry, Ocular
PubMed: 36727389
DOI: 10.4103/ijo.IJO_1889_22 -
International Journal of Hyperthermia :... 2020Hyperthermia (heating to 43 °C) activates the innate immune system and improves bladder cancer chemosensitivity.
BACKGROUND
Hyperthermia (heating to 43 °C) activates the innate immune system and improves bladder cancer chemosensitivity.
OBJECTIVE
To evaluate the tissue penetration and safety of convective hyperthermia combined with intravesical mitomycin C (MMC) pharmacokinetics in live porcine bladder models using the Combat bladder recirculation system (BRS).
METHODS
Forty 60 kg-female swine were anesthetized and catheterized with a 3-way, 16 F catheter. The Combat device was used to heat the bladders to a target temperature of 43 °C with recirculating intravesical MMC at doses of 40, 80, and 120 mg. Dwell-heat time varied from 30-180 min. Rapid necropsy with immediate flash freezing of tissues, blood and urine occurred. MMC concentrations were measured by liquid chromatography tandem-mass spectrometry.
RESULTS
The Combat BRS system was able to achieve target range temperature (42-44 °C) in 12 mins, and this temperature was maintained as long as the device was running. Two factors increased tissue penetration of MMC in the bladder: drug concentration, and the presence of heat. In the hyperthermia arm, MMC penetration saturated at 80 mg, suggesting that with heating, drug absorption may saturate and not require higher doses to achieve the maximal biological effect. Convective hyperthermia did not increase the MMC concentration in the liver, heart, kidney, spleen, lung, and lymph node tissue even at the 120 mg dose.
CONCLUSIONS
Convective bladder hyperthermia using the Combat BRS device is safe and the temperature can be maintained at 43 °C. Hyperthermia therapy may increase MMC penetration into the bladder wall but does not result in an increase of MMC levels in other organs.
Topics: Administration, Intravesical; Animals; Antibiotics, Antineoplastic; Female; Hyperthermia; Hyperthermia, Induced; Mitomycin; Swine; Urinary Bladder Neoplasms
PubMed: 32664768
DOI: 10.1080/02656736.2020.1780328 -
Journal of Ayub Medical College,... 2023Cryotherapy is a common destructive treatment modality for treating plantar warts that results in blistering and scarring. Mitomycin an antitumor drug with antiviral... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Cryotherapy is a common destructive treatment modality for treating plantar warts that results in blistering and scarring. Mitomycin an antitumor drug with antiviral property is a safe, better and a promising option for treating plantar warts. Objective was to compare efficacy of cryotherapy and mitomycin microneedling in the management of plantar warts. It was a randomized controlled trial conducted at the Skin Department CMH Abbottabad from 1st May to 31st December 2021.
METHODS
The study included 60 patients with plantar warts. Each group with 30 patients. Random tables were used to determine the distribution of patients within each group. Group A received mitomycin microneedling (1u/ml) repeated every 3 weeks. Group B was prescribed liquid nitrogen cryotherapy. The freeze-thaw cycle was 20 secs and repeated every 2 weeks. Both groups were treated for 4 months duration. For analysis of data, SPSS version 21.0 was used. Efficacy was compared by the application of Chi-square test between the two groups. p<0.05 was considered statistically significant.
RESULTS
Mitomycin microneedling completely cured 76.7% of patients, while cryotherapy was effective for only 56.7%. Complete remission was observed after two to three sessions of mitomycin microneedling while average of 4 sessions of cryotherapy were required for complete remission. In general, microneedling with mitomycin had better tolerance, pain being the commonest adverse effect.
CONCLUSIONS
Plantar warts can be effectively treated with mitomycin microneedling. Treatment of plantar warts with this method is more effective, requires fewer sessions, and may take less time to complete.
Topics: Humans; Mitomycin; Cryotherapy; Warts; Antiviral Agents; Cicatrix
PubMed: 36849393
DOI: 10.55519/JAMC-01-10932 -
Journal of Visualized Experiments : JoVE Oct 2017Combination chemotherapy is frequently used in the clinic for cancer treatment; however, associated adverse effects to normal tissue may limit its therapeutic benefit....
Combination chemotherapy is frequently used in the clinic for cancer treatment; however, associated adverse effects to normal tissue may limit its therapeutic benefit. Nanoparticle-based drug combination has been shown to mitigate the problems encountered by free drug combination therapy. Our previous studies have shown that the combination of two anticancer drugs, doxorubicin (DOX) and mitomycin C (MMC), produced a synergistic effect against both murine and human breast cancer cells in vitro. DOX and MMC co-loaded polymer-lipid hybrid nanoparticles (DMPLN) bypassed various efflux transporter pumps that confer multidrug resistance and demonstrated enhanced efficacy in breast tumor models. Compared to conventional solution forms, such superior efficacy of DMPLN was attributed to the synchronized pharmacokinetics of DOX and MMC and increased intracellular drug bioavailability within tumor cells enabled by the nanocarrier PLN. To evaluate the pharmacokinetics and bio-distribution of co-administered DOX and MMC in both free solution and nanoparticle forms, a simple and efficient multi-drug analysis method using reverse-phase high performance liquid chromatography (HPLC) was developed. In contrast to previously reported methods that analyzed DOX or MMC individually in the plasma, this new HPLC method is able to simultaneously quantitate DOX, MMC and a major cardio-toxic DOX metabolite, doxorubicinol (DOXol), in various biological matrices (e.g., whole blood, breast tumor, and heart). A dual fluorescent and ultraviolet absorbent probe 4-methylumbelliferone (4-MU) was used as an internal standard (I.S.) for one-step detection of multiple drug analysis with different detection wavelengths. This method was successfully applied to determine the concentrations of DOX and MMC delivered by both nanoparticle and solution approaches in whole blood and various tissues in an orthotopic breast tumor murine model. The analytical method presented is a useful tool for pre-clinical analysis of nanoparticle-based delivery of drug combinations.
Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Cell Line, Tumor; Disease Models, Animal; Doxorubicin; Drug Combinations; Drug Delivery Systems; Female; Humans; Mice; Mitomycin; Nanoparticles; Neoplasms
PubMed: 29053672
DOI: 10.3791/56159