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Determination of the mitigating effect of colon-specific bioreversible codrugs of mycophenolic acid and aminosugars in an experimental colitis model in Wistar rats

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World Journal of Gastroenterology 2018年第10期24卷 1093-1106页

作者： Shakuntala santosh chopade Suneela Sunil Dhaneshwar Department of Pharmaceutical chemistry Poona College of Pharmacy Bharati Vidyapeeth University

AIM To design colon-targeted codrugs of mycophenolic acid(MPA) and aminosugars as a safer option to mycophenolate mofetil(MMF) in the management of inflammatory bowel disease. METHODS codrugs were synthesized by coupling MPA with aminosugars(D-glucosamine and D-galactosamine) using EDcI coupling. The structures were confirmed by infrared radiation, nuclear magnetic resonance, mass spectroscopy and elemental analysis. The release profile of codrugs was extensively studied in aqueous buffers, upper gastrointestinal homogenates, faecal matter and caecal homogenates(in vitro) and rat blood(in vitro). Anti-colitic activity was assessed in 2,4,6-trinitrobezenesulfonic acid-induced colitis in Wistar rats by the estimation of various demarcating parameters. Statistical evaluation was performed by applying one-way and two-way ANOVA when compared with the disease *** The prodrugs resisted activation in Hcl buffer(pH 1.2) and stomach homogenates of rats with negligible hydrolysis in phosphate buffer(p H 7.4) and intestinal homogenates. Incubation with colon homogenates(in vitro) produced 76% to 89% release of MPA emphasizing colon-specific activation of codrugs and the release of MPA and aminosugars at the site of action. In the in vitro studies, the prodrug of MPA with D-glucosamine(MGLS) was selected which resulted in 68% release of MPA in blood. in vitro studies on MGLS revealed its colon-specific activation after a lag time of 8 h which could be ascribed to the hydrolytic action of N-acyl amidases found in the colon. The synthesized codrugs markedly diminished disease activity score and revived the disrupted architecture of the colon that was comparable to MMF but superior to MPA. cONcLUSION The significant attenuating effect of prodrugs and individual aminosugars on colonic inflammation proved that the rationale of the codrug approach is valid.

关键词： Mycophenolic acid Mutual prodrug Inflammatory bowel disease Mycophenolate mofetil

Anal carcinoma in giant anal condyloma, multidisciplinary approach necessary for optimal outcome:Two case reports and review of literature

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World Journal of Gastrointestinal Oncology 2019年第2期11卷 172-180页

作者： santosh Shenoy Murali Nittala Yazen Assaf Department of General and colorectal Surgery KCVA and University of Missouri at Kansas City

BAckGROUND Anal cancers are caused by human papilloma virus(HPV). Buschke-Lowenstein tumor also known as giant anal condyloma(GcA) is a variant of giant neglected anal tumors arising from warts caused by HPV infection. HPV are a family of double-stranded DNA viruses and primarily cause sexually transmitted disease of the genitalia and oropharyngeal mucosa. These tumors are slow growing;locally destructive large verrucous *** SUMMARY We present a series of two cases with large anal tumors harboring invasive cancers and highlight their presentation and management. Tumors with high risk HPV subtypes(HPV 16, 18, 31, 33) may progress into invasive squamous cell carcinoma(Scc). Untreated GcA can attain enormous size and extend into the pelvic organs and bony structures. Some tumors show malignant degeneration into Scc and are often difficult to diagnose given the large size of the *** surgical excision with negative margins is the treatment of choice and necessary to prevent recurrence. This is often not feasible and leaves large surgical wounds with tissue defects with delay in healing and increases postoperative morbidity. Pelvic reconstructive techniques including muscle flaps and grafts are often necessary to close the defects. Human immunodeficiency virus and immunocompromised patients generally do poorly with standard *** A multidisciplinary team of colorectal and plastic surgeons, medical and radiation oncologists along with combination treatment modalities are necessary when malignant transformation occurs in GcA, for optimal outcomes.

关键词： Squamous cell carcinoma of anus Human papilloma virus infection Giant anal condyloma Buschke-Lowenstein tumor Multidisciplinary treatment case report

Barrett’s esophagus:Review of natural history and comparative efficacy of endoscopic and surgical therapies

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World Journal of Gastrointestinal Oncology 2022年第3期14卷 568-586页

作者： kevin kyung Ho choi santosh Sanagapalli AW Morrow Gastroenterology Liver centre Royal Prince Alfred HospitalSydney 2050NSWAustralia Department of Gastroenterology St Vincent’s HospitalDarlinghurst 2010NSWAustralia

Barrett's esophagus(BE)is the precursor to esophageal adenocarcinoma(EAc).Progression to cancer typically occurs in a stepwise fashion through worsening dysplasia and ultimately,invasive *** EAc with deep involvement of the esophageal wall and/or metastatic disease is invariably associated with poor long-term survival *** guides the rationale of surveillance of Barrett’s in an attempt to treat lesions at an earlier,and potentially curative *** last two decades have seen a paradigm shift in management of Barrett’s with rapid expansion in the role of endoscopic eradication therapy(EET)for management of dysplastic and early neoplastic BE,and there have been substantial changes to international consensus guidelines for management of early BE based on evolving *** review aims to assist the physician in the therapeutic decision-making process with patients by comprehensive review and summary of literature surrounding natural history of Barrett’s by histological stage,and the effectiveness of interventions in attenuating the risk posed by its natural *** findings were as ***-dysplastic Barrett’s is associated with extremely low risk of progression,and interventions cannot be *** annual risk of cancer progression in low grade dysplasia is between 1%-3%;EET can be offered though evidence for its benefit remains confined to highly select ***-grade dysplasia progresses to cancer in 5%-10%per year;EET is similarly effective to and less morbid than surgery and should be routinely performed for this *** of nodal metastases in intramucosal cancer is 2%-4%,which is comparable to operative mortality rate,so EET is usually *** cancer is associated with nodal metastases in 14%-41%hence surgery remains standard of care,except for select situations.

关键词： Barrett’s esophagus Endoscopic eradication therapy Dysplasia Adenocarcinoma Natural history Radiofrequency ablation

Supercontinent tectonics and biogeochemical cycle:A matter of 'life and death'

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Geoscience Frontiers 2010年第1期1卷 21-30页

作者： M.santosh Division of Interdisciplinary Science Faculty of ScienceKochi UniversityKochi 780-8520Japan

The formation and disruption of supercontinents have significantly impacted mantle dynamics, solid earth processes, surface environments and the biogeochemical cycle. In the early history of the Earth, the collision of parallel intra-oceanic arcs was an important process in building embryonic continents. Superdownwelling along Y-shaped triple junctions might have been one of the important processes that aided in the rapid assembly of continental fragments into closely packed supercontinents. Various models have been proposed for the fragmentation of supercontinents including thermal blanket and superplume hypotheses. The reassembly of supercontinents after breakup and the ocean closure occurs through ＂introversion＂, ＂extroversion＂ or a combination of both, and is characterized by either Pacific-type or Atlantic-type ocean closure. The breakup of supercontinents and development of hydro- thermal system in rifts with granitic basement create anomalous chemical environments enriched in nutri- ents, which serve as the primary building blocks of the skeleton and bone of early modern life forms. A typical example is the rifting of the Rodinia supercontinent, which opened up an N--S oriented sea way along which nutrient enriched upwelling brought about a habitable geochemical environment. The assembly of supercontinents also had significant impact on life evolution. The role played by the cambrian Gondwana assembly has been emphasized in many models, including the formation of ＇Trans- gondwana Mountains＇ that might have provided an effective source of rich nutrients to the equatorial waters, thus aiding the rapid increase in biodiversity. The planet has witnessed several mass extinction events during its history, mostly connected with major climatic fluctuations including global cooling and warming events, major glaciations, fluctuations in sea level, global anoxia, volcanic eruptions, asteroid impacts and gamma radiation. Some recent models speculate a relationship betwee

关键词： Supercontinents Mantle dynamics Superplume Life evolution Extinction cambrian explosion

Arsenic contamination of groundwater:A global synopsis with focus on the Indian Peninsula

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Geoscience Frontiers 2021年第3期12卷 1-18页

作者： E.Shaji M.santosh k.V.Sarath Pranav Prakash V.Deepchand B.V.Divya Department of Geology University of KeralaKariavattom CampusTrivandrum 695581India School of Earth Sciences and Resources China University of Geosciences(Beijing)29 Xueyuan RoadBeijing 100083China Department of Earth Science University of AdelaideAdelaideSA 5005Australia

More than 2.5 billion people on the globe rely on groundwater for drinking and providing high-quality drinking water has become one of the major challenges of human *** groundwater is considered as safe,high concentrations of heavy metals like arsenic(As)can pose potential human health concerns and *** this paper,we present an overview of the current scenario of arsenic contamination of groundwater in various countries across the globe with an emphasis on the Indian *** several newly affected regions reported during the last decade,a significant increase has been observed in the global scenario of arsenic *** is estimated that nearly 108 countries are affected by arsenic contamination in groundwater with concentration beyond maximum permissible limit of 10 ppb recommended by the World Health *** highest among these are from Asia(32)and Europe(31),followed by regions like Africa(20),North America(11),South America(9)and Australia(4).More than 230 million people worldwide,which include 180 million from Asia,are at risk of arsenic *** Asian countries,Bangladesh,India,Pakistan,china,Nepal,Vietnam,Burma,Thailand and cambodia,are the most *** India,20 states and 4 Union Territories have so far been affected by arsenic contamination in *** attempt to evaluate the correlation between arsenic poisoning and aquifer type shows that the groundwater extracted from unconsolidated sedimentary aquifers,particularly those which are located within the younger orogenic belts of the world,are the worst *** than 90%of arsenic pollution is inferred to be *** infer that alluvial sediments are the major source for arsenic contamination in groundwater and we postulate a strong relation with plate tectonic processes,mountain building,erosion and *** consumption of arsenic-contaminated groundwater results in severe health issues like skin,lung,kidney and bladder ca

关键词： Arsenic contamination Groundwater Indo-Gangetic alluvium Orogenic belts Global tectonics Asia

The naked planet Earth:Most essential pre-requisite for the origin and evolution of life

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Geoscience Frontiers 2013年第2期4卷 141-165页

作者： S.Maruyama M.Ikoma H.Genda k.Hirose T.Yokoyama M.santosh Department of Earth and Planetary Sciences Tokyo Institute of Technology2-12-1 OokayamaMeguro-kuTokyo 152-8551Japan Department of Earth and Planetary Science.The University of Tokyo 7-3-1 HongoBunkyo-kuTokyo 113-0033.Japan Department of Earth and Planetary Sciences.Tokyo Institute of Technology 2-12-1 OokayamaMeguro-ku.Tokyo 152-8551Japan School of Earth Sciences and Resources China University of Geosciences(Beijing) Faculty of Science Kochi UniversityKochi 780-8520Japan

Our blue planet Earth has long been regarded to carry full of nutrients for hosting life since the birth of the *** we speculate the processes that led to the birth of early life on Earth and its aftermath, finally leading to the evolution of *** evaluate：（1） the source of nutrients,（2） the chemistry of primordial ocean,（3） the initial mass of ocean,and（4） the size of *** the life-building nutrients,phosphorus and potassium play a key *** three types of rocks can serve as an adequate source of nutrients：（a） continent-forming TTG（granite）,enabling the evolution of primitive life to metazoans;（b） primordial continents carrying anorthosite with kREEP（Potassium,Rare Earth Elements, and Phosphorus） basalts,which is a key to bear life;（c） carbonatite magma,enriched in radiogenic elements such as U and Th,which can cause mutation to speed up evolution and promote the birth of new species in continental rift *** second important factor is ocean *** primordial ocean was extremely acidic（pH = 1-2） and enriched in halogens（cI,F and others）,S,N and metallic elements（cd,cu,Zn,and others）,inhibiting the birth of *** tectonics cleaned up these elements which interfered with *** ocean finally appeared in the Phanerozoic with pH = 7 through extensive interaction with surface continental crust by weathering,erosion and transportation into *** initial ocean mass was also *** birth of life and aftermath of evolution was possible in the habitable zone with 3-5 km deep ocean which was able to supply sufficient nutrients. Without a huge landmass,nutrients cannot be supplied into the ocean only by ridge-hydrothermal circulation in the ***,the size of the planet plays a crucial *** of massive planets is less efficient than smaller ones,so that return-flow of seawater into mantle does not occur until central stars finish their main *** to the suitable size of Earth,the dawn of Phaneroz

关键词： Earth Life Habitable planet Initial ocean mass Metazoan Nutrients

challenges in diagnosis of pancreatic cancer

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World Journal of Gastroenterology 2018年第19期24卷 2047-2060页

作者： Lulu Zhang santosh Sanagapalli Alina Stoita Department of Gastroenterology St. Vincent's Hospital Sydney

Pancreatic cancer is a growing source of cancer related death, yet has poor survival rates which have not improved in the last few decades. Its high mortality rate is attributed to pancreatic cancer biology, difficulty in early diagnosis and the lack of standardised international guidelines in assessing suspicious pancreatic masses. This review aims to provide an update in the current state of play in pancreatic cancer diagnosis and to evaluate the benefits and limitations of available diagnostic technology. The main modalities discussed are imaging with computed tomography, magnetic resonance imaging, endoscopic ultrasound and positron emission tomography and tissue acquisition with fine needle aspiration. We also review the improvements in the techniques used for tissue acquisition and the opportunity for personalised cancer medicine. Screening of high risk individuals, promising biomarkers and common mimickers of pancreatic cancer are also explored, as well as suggestions for future research directions to allow for earlier detection of pancreatic cancer. Timely and accurate diagnosis of pancreatic cancer can lead to improvements in the current poor outcome of this disease.

关键词： Pancreatic cancer Diagnosis challenges Imaging Biomarkers Screening Endoscopic ultrasound Pitfalls

Recent advances,challenges,and opportunities of inorganic nanoscintillators

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Frontiers of Optoelectronics 2020年第2期13卷 156-187页

作者： santosh kGUPTA Yuanbing MAO Radiochemistry Division Bhabha Atomic Research CentreTrombayMumbai 400085India Department of chemistry Illinois Institute of TechnologyChicagoIL 60616USA

This review article highlights the exploration of inorganic nanoscintillators for various scientific and technological applications in the fields of radiation detection,bioimaging,and medical *** aspects of nanoscintillators pertaining to their fundamental principles,mechanism,structure,applications are briefly *** mechanisms of inorganic nanoscintillators are explained based on the fundamental principles,instrumentation involved,and associated physical and chemical phenomena,***,the promise of nanoscintillators over the existing single-crystal scintillators and other types of scintillators is presented,enabling their development for multifunctional *** processes governing the scintillation mechanisms in nanodomains,such as surface,structure,quantum,and dielectric confinement,are explained to reveal the underlying nanoscale scintillation ***,suitable examples are provided to explain these processes based on the published ***,we attempt to explain the different types of inorganic nanoscintillators in terms of the powder nanoparticles,thin films,nanoceramics,and glasses to ensure that the effect of nanoscience in different nanoscintillator domains can be *** limitations of nanoscintillators arc also highlighted in this review *** advantages of nanostructured scintillators,including their property-driven applications,are also *** review article presents the considerable application potential of nanostructured scintillators with respect to important aspects as well as their physical and application significance in a concise manner.

关键词： scintillators nanoscintillators inorganic photoluminescence radioluminescence

The gold-telluride connection:Evidence for multiple fluid pulses in the Jinqingding telluride-rich gold deposit of Jiaodong Peninsula,Eastern china

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Geoscience Frontiers 2024年第3期15卷 146-165页

作者： Wenyan cai Mingchun Song M.santosh Jian Li School of Resources and Environmental Engineering Shandong University of TechnologyZibo 255049China Hebei key Laboratory of Strategic critical Mineral Resources Hebei GEO UniversityShijiazhuang 050031China School of Earth Sciences and Resources China University of Geosciences Beijing29 Xueyuan RoadBeijing 100083China Department of Earth Science University of AdelaideAdelaide SA 5005Australia

The mechanism of gold migration,enrichment,and precipitation in forming world-class gold deposits has been a topic of wide interest,particularly where these deposits are abundant in *** Jiaodong Peninsula in eastern china hosts some of the world-class gold deposits among which the Jinqingding deposit is one of the best examples with substantial telluride mineralization and thus provides opportunity to investigate the genetic connection between tellurium and gold *** orebody in this deposit is hosted in the NE-NNE-trending Jiangjunshi-Quhezhuang fault with the Jurassic kunyushan granitic pluton as wall *** deposit involved three mineralization stages as inferred from assemblages and crosscutting relationships between *** stages are:(I)pre-ore gold-poor quartz-pyrite veins,(II)main ore auriferous quartz-pyrite-Te/Bi-minerals±sphalerite±chalcopyrite±barite±marcasite veins,and(III)post-ore quartz-calcite *** present here the textural,isotopic,and geochemical variations of different stages/generations of pyrite based on scanning electron microscopy-energy dispersive spectroscopy(SEM-EDS),electron probe microanalysis(EPMA),and laser ablation inductively coupled plasma mass spectrometry(LA-IcP-MS).Pyrite in the Jinqingding deposit displays distinct ***1a shows a porous and dissolution-reprecipitation texture in the core,whereas Py1b exhibits a smooth and flat *** analysis reveals contrasting elemental compositions,with Py1a characterized by low Au(avg.0.14 ppm),As(avg.15.57 ppm),Ag(avg.17.71 ppm),and Te(avg.19.22 ppm)contents,but elevated co(avg.1068.10 ppm)and Ni(224.12 ppm)concentrations,and variable sulfur isotopic composition(δ^(34)SV-cDT=9.54‰-12.12‰).conversely,Py1b displays increased concentrations of these elements and a more concentratedδ^(34)SV-cDT value(11.99‰-12.23‰),possibly associated with weak coupled dissolution-reprecipitation(cDR)*** Stage II,pyrite can be further categorized

关键词： Episodic fluid pulses Sulfur reservoir Gold-Te precipitation Jinqingding deposit Jiaodong Peninsula