In vivo molecular imaging has become a key technology for pathophysiological science and drug development. We are mostly utilizing PET(positron emission tomography) as a first-choice modality, because of its ultra-high sensitivity for molecules, adequate temporal and spatial resolution, and especially broad spectrum of target molecules. In vivo molecular imaging could bring the high-quality information about: 1. Molecular diagnosis for living patients with symptoms 2. Closer approach for etiology and differential diagnosis 3. Direct follow-up of key molecules as disease markers 4. Pharmacokinetics/Pharmacodynamics in primates/human 5. Dose finding information for individuals, corresponding to SNPs 6. Direct evidence for accumulation in non-target organs related to adverse effects 7. Drug effects with surrogate markers 8. Early decision of dropout substances (drug candidates) Here, the examples are shown as beta-amyloid imaging for Alzheimer's and mild cognitive impairment, serotonin transporter imaging for chronic fatigue, and dopaminergic components imaging for evaluation of drug for autistic spectrum disorder. In 2005, RIKEN and National Institute of Radiological Science were selected as the key centers for development of All-Japan research network to further promote mutual international and multi -disciplinary collaboration on in vivo molecular imaging.

Molecular imaging for drug development

The Political Economy of Agrarian Change: An Essay on the Green Revolution

Findings presented here about farmer suicides in Amravati and Yavatmal districts, Maharashtra, are evaluated in relation to Durkheimian theory, which attributes such acts to an historically specific combination of social and economic causes. Lower and middle caste peasant smallholders found themselves trapped between enhanced aspirations generated by land reform and other post-1947 measures, and the reality of neoliberalism (rising debt, declining income). Suicides among large and medium farmers belonging to the higher castes in Maharashtra were occasioned by failures in business, trade and politics. Such cases are consistent with the argument put forward by Durkheim, that suicide is an effect of individualization, a process of socio-economic ‘estrangement’ from agrarian communities experienced by rural producers in the context of rapid economic growth.

‘We are Like the Living Dead’: Farmer Suicides in Maharashtra, Western India

Overcoming barriers by local drug delivery with liposomes

Nanomaterials offer unique physical, chemical and biological properties of interest for medical imaging and therapy. Over the last two decades, there has been an increasing effort to translate nanomaterial-based medicinal products (so-called nanomedicines) into clinical practice and, although multiple nanoparticle-based formulations are clinically available, there is still a disparity between the number of pre-clinical products and those that reach clinical approval. To facilitate the efficient clinical translation of nanomedicinal-drugs, it is important to study their whole-body biodistribution and pharmacokinetics from the early stages of their development. Integrating this knowledge with that of their therapeutic profile and/or toxicity should provide a powerful combination to efficiently inform nanomedicine trials and allow early selection of the most promising candidates. In this context, radiolabelling nanomaterials allows whole-body and non-invasive in vivo tracking by the sensitive clinical imaging techniques positron emission tomography (PET), and single photon emission computed tomography (SPECT). Furthermore, certain radionuclides with specific nuclear emissions can elicit therapeutic effects by themselves, leading to radionuclide-based therapy. To ensure robust information during the development of nanomaterials for PET/SPECT imaging and/or radionuclide therapy, selection of the most appropriate radiolabelling method and knowledge of its limitations are critical. Different radiolabelling strategies are available depending on the type of material, the radionuclide and/or the final application. In this review we describe the different radiolabelling strategies currently available, with a critical vision over their advantages and disadvantages. The final aim is to review the most relevant and up-to-date knowledge available in this field, and support the efficient clinical translation of future nanomedicinal products for in vivo imaging and/or therapy.

/pdf/radiolabelling-of-nanomaterials-for-medical-imaging-and-1wnnia4i8w.pdf

Radiolabelling of nanomaterials for medical imaging and therapy.

Enhanced skin permeation of Methotrexate from penetration enhancer containing vesicles: In vitro optimization and in vivo evaluation.

The uncommonness of gallbladder cancer in the developed world has contributed to the generally poor understanding of the disease. Our integrated analysis of whole exome sequencing, copy number alterations, immunohistochemical, and phospho-proteome array profiling indicates ERBB2 alterations in 40% early-stage rare gallbladder tumors, among an ethnically distinct population not studied before, that occurs through overexpression in 24% (n = 25) and recurrent mutations in 14% tumors (n = 44); along with co-occurring KRAS mutation in 7% tumors (n = 44). We demonstrate that ERBB2 heterodimerizes with EGFR to constitutively activate the ErbB signaling pathway in gallbladder cells. Consistent with this, treatment with ERBB2-specific, EGFR-specific shRNA or with a covalent EGFR family inhibitor Afatinib inhibits tumor-associated characteristics of the gallbladder cancer cells. Furthermore, we observe an in vivo reduction in tumor size of gallbladder xenografts in response to Afatinib is paralleled by a reduction in the amounts of phospho-ERK, in tumors harboring KRAS (G13D) mutation but not in KRAS (G12V) mutation, supporting an essential role of the ErbB pathway. In overall, besides implicating ERBB2 as an important therapeutic target under neo-adjuvant or adjuvant settings, we present the first evidence that the presence of KRAS mutations may preclude gallbladder cancer patients to respond to anti-EGFR treatment, similar to a clinical algorithm commonly practiced to opt for anti-EGFR treatment in colorectal cancer.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.31916

ERBB2 and KRAS alterations mediate response to EGFR inhibitors in early stage gallbladder cancer

Anchoring of endosseous implant through osseointegration continues to be an important clinical need. Here, we describe the development of superior endosseous implant demonstrating enhance osseointegration, achieved through surface modification via coating of osteogenic nanofibres. The randomized bio-composite osteogenic nanofibres incorporating polycaprolactone, gelatin, hydroxyapatite, dexamethasone, beta-glycerophosphate and ascorbic acid were electrospun on titanium implants mimicking bone extracellular matrix and subsequently induced osteogenesis by targeting undifferentiated mesenchymal stem cells present in the peri-implant niche to regenerate osseous tissue. In proof-of-concept experiment on rabbit study models (n = 6), micro-computed tomography (Micro-CT), histomorphometric analysis and biomechanical testing in relation to our novel osteogenic nanofibrous coated implants showed improved results when compared to uncoated controls. Further, no pathological changes were detected during gross examination and necropsy on peri-implant osseous tissues regenerated in response to such coated implants. The findings of the present study confirm that osteogenic nanofibrous coating significantly increases the magnitude of osteogenesis in the peri-implant zone and favours the dynamics of osseointegration.

/pdf/accentuated-osseointegration-in-osteogenic-nanofibrous-18lcae2zlu.pdf

Accentuated osseointegration in osteogenic nanofibrous coated titanium implants

Critical Perspectives on Agrarian Transition : India in the global debate

Oral administration of 3,3'-diselenodipropionic acid prevents thoracic radiation induced pneumonitis in mice by suppressing NF-kB/IL-17/G-CSF/neutrophil axis.

Bhabani Mohanty

Papers

Enhanced skin permeation of Methotrexate from penetration enhancer containing vesicles: In vitro optimization and in vivo evaluation.

ERBB2 and KRAS alterations mediate response to EGFR inhibitors in early stage gallbladder cancer

Accentuated osseointegration in osteogenic nanofibrous coated titanium implants

Critical Perspectives on Agrarian Transition : India in the global debate

Oral administration of 3,3'-diselenodipropionic acid prevents thoracic radiation induced pneumonitis in mice by suppressing NF-kB/IL-17/G-CSF/neutrophil axis.