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Garg Pankaj,Mongia Anvesha 대한대장항문학회 2024 Annals of Coloproctolgy Vol.40 No.1
Anal fistulas, especially complex and high fistulas, are difficult to manage. The transanal opening of the intersphincteric space (TROPIS) procedure was first described in 2017, and a high success rate of over 90% was reported in high complex fistulas. Since then, more studies and even a meta-analysis have corroborated the high efficacy of this procedure in high fistulas. Conventionally, the main focus was to close the internal (primary) opening for the fistula to heal. However, most complex fistulas have a component of the fistula tract in the intersphincteric plane. This component is like an abscess (sepsis) in a closed space (2 muscle layers). It is a well-known fact that in the presence of sepsis, healing by secondary intention leads to better results than attempting to heal by primary intention. Therefore, TROPIS is the first procedure in which, instead of closing the internal opening, the opening is widened by laying open the fistula tract in the intersphincteric plane so that healing can occur by secondary intention. Although the drainage of high intersphincteric abscesses through the transanal route was described 5 decades ago, the routine utilization of TROPIS for the definitive management of high complex fistulas was first described in 2017. The external anal sphincter (EAS) is completely spared in TROPIS, as the fistula tract on either side of the EAS is managed separately—inner (medial) to the EAS by laying open the intersphincteric space and outer (lateral) to the EAS by curettage or excision.
JNK2 silencing and caspase-9 activation by hyperosmotic polymer inhibits tumor progression
Garg, Pankaj,Pandey, Shambhavi,Hoon, Seonwoo,Jang, Kyoung-Je,Lee, Myung Chul,Choung, Yun-Hoon,Choung, Pill-Hoon,Chung, Jong Hoon Elsevier 2018 International journal of biological macromolecules Vol.120 No.2
<P><B>Abstract</B></P> <P>c-Jun N-terminal kinase 2 (JNK2) is primarily responsible for the oncogenic transformation of the transcription factor c-Jun. Expression of the proto-oncogene c-Jun progresses the cell cycle from G1 to S phase, but when its expression becomes awry it leads to uncontrolled proliferation and angiogenesis. Delivering a JNK2 siRNA (siJNK2) in tumor tissue was anticipated to reverse the condition with subsequent onset of apoptosis which predominantly requires an efficient delivering system capable of penetrating through the compact tumor mass. In the present study, it was demonstrated that polymannitol-based vector (PMGT) with inherent hyperosmotic properties was able to penetrate through and deliver the siJNK2 in the subcutaneous tumor of xenograft mice. Hyperosmotic activity of polymannitol was shown to account for the enhanced therapeutic delivery both in vitro and in vivo because of the induction of cyclooxygenase-2 (COX-2) which stimulates caveolin-1 for caveolae-mediated endocytosis of the polyplexes. Further suppression of JNK2 and hence c-Jun expression led to the activation of caspase-9 to induce apoptosis and inhibition of tumor growth in xenograft mice model. The study exemplifies PMGT as an efficient vector for delivering therapeutic molecules in compact tumor tissue and suppression of JNK2 introduces a strategy to inhibit tumor progression.</P> <P><B>Graphical abstract</B></P> <P>Hyperosmotic PMGT driven siJNK2 delivery in compact cancer cells inhibits c-jun phosphorylation resulting in tumor growth arrest via caspase-9 induction and apoptosis.</P> <P>[DISPLAY OMISSION]</P>
Kumar, Santosh,Garg, Pankaj,Pandey, Shambhavi,Kumari, Mridula,Hoon, Seonwoo,Jang, Kyoung-Je,Kapavarapu, Ravikumar,Choung, Pill-Hoon,Sobral, Abilio J. F. N.,Hoon Chung, Jong The Royal Society of Chemistry 2015 Journal of Materials Chemistry B Vol.3 No.17
<P>Gene therapy is the treatment of human disorders by the introduction of genetic material to specific target cells of a patient. Chitosan and its derivatives show excellent biological properties including biocompatibility, biodegradability and nonallergenicity. Primary amines of chitosan are responsible for its cationic nature and hence binding and protection of DNA for intracellular delivery. But the transfection efficiency of chitosan based gene transporters is severely hampered by its poor physical properties such as low water solubility and high viscosity. In this study, primary amines of low molecular weight (LMW) chitosan were coupled with 2-acrylamido-2-methylpropane sulphonic acid (AMP) making it water soluble for its application in gene delivery. AMP modified chitosan (CSAMP) showed an enhanced interaction with DNA and a higher buffering capacity due to AMP amines leading to a higher transfection efficiency in cancer cells (A549, HeLa and HepG2) compared to native chitosan and Lipofectamine®. <I>In vivo</I> studies in Balb/c through intravenous injection demonstrated a higher luciferase expression compared to LMW chitosan.</P>
Bhupendra Kumar Jain,Kumar Vaibhaw,Pankaj Kumar Garg,Sanjay Gupta,Debajyoti Mohanty 대한대장항문학회 2012 Annals of Coloproctolgy Vol.28 No.2
Purpose: This randomized clinical trial was conducted to compare a fistulectomy and a fistulotomy with marsupialization in the management of a simple anal fistula. Methods: Forty patients with simple anal fistula were randomized into two groups. Fistulous tracts were managed by using a fistulectomy (group A) while a fistulotomy with marsupialization was performed in group B. The primary outcome measure was wound healing time while secondary outcome measures were operating time, postoperative wound size, postoperative pain, wound infection, anal incontinence, recurrence and patient satisfaction. Results: Postoperative wounds in group B healed earlier in comparison to group A wounds (4.85 ± 1.39 weeks vs. 6.75 ±1.83 weeks, P = 0.035). No significant differences existed between the operating times (28.00 ± 6.35 minutes vs. 28.20 ± 6.57minutes, P = 0.925) and visual analogue scale scores for postoperative pain on the first postoperative day (4.05 ± 1.47 vs. 4.50 ± 1.32, P = 0.221) for the two groups. Postoperative wounds were larger in group A than in group B (2.07 ± 0.1.90 cm2vs.1.23 ± 0.87 cm2), however this difference did not reach statistical significance (P = 0.192). Wound discharge was observed for a significantly longer duration in group A than in group B (4.10 ± 1.91 weeks vs. 2.75 ± 1.71 weeks, P = 0.035). There were no differences in social and sexual activities after surgery between the patients of the two groups. No patient developed anal incontinence or recurrence during the follow-up period of twelve weeks. Conclusion: In comparison to a fistulectomy, a fistulotomy with marsupialization results in faster healing and a shorter duration of wound discharge without increasing the operating time. Purpose: This randomized clinical trial was conducted to compare a fistulectomy and a fistulotomy with marsupialization in the management of a simple anal fistula. Methods: Forty patients with simple anal fistula were randomized into two groups. Fistulous tracts were managed by using a fistulectomy (group A) while a fistulotomy with marsupialization was performed in group B. The primary outcome measure was wound healing time while secondary outcome measures were operating time, postoperative wound size, postoperative pain, wound infection, anal incontinence, recurrence and patient satisfaction. Results: Postoperative wounds in group B healed earlier in comparison to group A wounds (4.85 ± 1.39 weeks vs. 6.75 ±1.83 weeks, P = 0.035). No significant differences existed between the operating times (28.00 ± 6.35 minutes vs. 28.20 ± 6.57minutes, P = 0.925) and visual analogue scale scores for postoperative pain on the first postoperative day (4.05 ± 1.47 vs. 4.50 ± 1.32, P = 0.221) for the two groups. Postoperative wounds were larger in group A than in group B (2.07 ± 0.1.90 cm2vs.1.23 ± 0.87 cm2), however this difference did not reach statistical significance (P = 0.192). Wound discharge was observed for a significantly longer duration in group A than in group B (4.10 ± 1.91 weeks vs. 2.75 ± 1.71 weeks, P = 0.035). There were no differences in social and sexual activities after surgery between the patients of the two groups. No patient developed anal incontinence or recurrence during the follow-up period of twelve weeks. Conclusion: In comparison to a fistulectomy, a fistulotomy with marsupialization results in faster healing and a shorter duration of wound discharge without increasing the operating time.
Lee, Myung Chul,Seonwoo, Hoon,Garg, Pankaj,Jang, Kyoung Je,Pandey, Shambhavi,Park, Sang Bae,Kim, Hong Bae,Lim, Jaewoon,Choung, Yun Hoon,Chung, Jong Hoon RSC Publications 2018 Biomaterials Science Vol.6 No.2
<P>Damage to the eardrum causes acute pain and can lead to chronic otitis media if it develops into chronic tympanic membrane (TM) perforations. Chronic TM perforations are usually treated with surgical methods such as tympanoplasty and myringoplasty. However, these surgeries are not only complicated and difficult but also cost a lot of money. Our research team developed chitosan patches (E-CPs) that release epidermal growth factor (EGF) as a patch therapy to replace surgical methods. However, there was a limitation in the healing ratio of the treatment compared to the surgical methods. In this study, we developed EGF and epidermal growth factor receptor (EGFR) gene-releasing polyethyleneimine (PEI)/chitosan patches (EErP-CPs) to increase the regeneration of TM perforations. The addition of PEI increased the adhesion and migration ability of TM cells on the patches. The simultaneous release of the EGF and the EGFR gene further enhanced TM cell proliferation, adhesion and migratory ability. It was confirmed that the EGF protein and EGFR gene were released for 30 days; however, EGF was released and increased TM cell viability almost immediately after treatment and EGFR took a minimum of 3 days before showing its effect on improved cell viability. It was also shown that EErP-CPs are more hydrophilic and have more positive charge than E-CP because of added amine groups from PEI. In conclusion, the developed EErP-CPs resulted in the improved healing of TM perforations and can potentially be applied to the regeneration of both chronic and acute tympanic membrane perforations.</P>