Role of Calcium in Vomiting

Cisplatin-like chemotherapeutics cause vomiting via calcium (Ca2+)-dependent release of multiple neurotransmitters/mediators (dopamine, serotonin, substance P, prostaglandins and leukotrienes) from the gastrointestinal enterochromaffin cells and/or the brainstem. Intracellular Ca2+ signaling is triggered by activation of diverse emetic receptors (including neurokininergic NK1, serotonergic 5-HT3, dopaminergic D2, cholinergic M1, or histaminergic H1), whose stimulation in vomit-competent species evokes emesis. Other emetogens such as cisplatin, rotavirus NSP4 protein, and bacterial toxins can also induce intracellular Ca2+ elevation. Our findings demonstrate that application of the L-type Ca2+ channel (LTCC) agonist FPL 64176 and the intracellular Ca2+ mobilizing agent thapsigargin (a sarco/endoplasmic reticulum Ca2+-ATPase inhibitor) cause vomiting in the least shrew. On the other hand, blockade of LTCCs by corresponding antagonists (nifedipine or amlodipine) not only provide broad-spectrum antiemetic efficacy against diverse agents that specifically activate emetogenic receptors such as 5-HT3, NK1, D2, and M1 receptors, but can also potentiate the antiemetic efficacy of palonosetron against the nonspecific emetogen, cisplatin. In this review, we will provide an overview of Ca2+ involvement in the emetic process; discuss the relationship between Ca2+ signaling and the prevailing therapeutics in control of vomiting; highlight the current evidence for Ca2+-signaling blockers/inhibitors in suppressing emetic behavior and also draw attention to the clinical benefits of Ca2+-signaling blockers/inhibitors for the treatment of nausea and vomiting

Tourist Flow and Tourism Potential Regions of Gulmarg in Kashmir Himalayas

Gulmarg has a rich and diverse touristic product that holds the potential to be one of the most attractive tourist destinations for both leisure and sports tourism across the whole Kashmir Himalayan region The place owes its importance mainly to its beautiful geo-environmental setup and unique climate The destination has a history of tourism activities for more than five centuries The resort has been a great attraction for several British officials posted in India and their families made Gulmarg their home for the summer months This his to-geographical personality of the place has resulted in the development of tourist regions of interest to a range of tastes especially for holiday makers and sports and adventure tourists Therefore present study aims at identification and delineation of the different tourist potential regions of the place which would help in proper marketing of the tourist product management of tourist flow optimization of economic returns and management of the environmental health of the destination for sustainable tourism development in the regio

BIOACTIVITY-GUIDED PHYTOCHEMICAL INVESTIGATIONS OF ARTEMISIA MARITIMA: ISOLATION AND CHARACTERIZATION OF CHEMICAL CONSTITUENTS

Objective: In the present study, the extracts (petroleum ether and methanolic extract) of plant Artemisia maritima were subjected to bioactivity evaluation and compound isolation and characterization.Methods: Antioxidant activity was carried out using ferric reducing power and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The anticancer activity was evaluated by MTT assay using three different human cancer cell lines: Embryonic kidney cancer cell (HEK), lung adenocarcinoma epithelial cell (A-549), and human colon cancer cell (HCT), and isolated compounds were characterized using nuclear magnetic resonance (1HNMR), 13CNMR, DEPT, infrared, and mass spectroscopic techniques.Results: The petroleum ether extract of the plant displayed significant antioxidant and cytotoxic effects, which on phytochemical analysis led to the isolation of two bioactive sesquiterpene lactone compounds. These phytochemicals were identified using different spectral techniques in the light of literature. All the compounds displayed significant cytotoxic activity; however, compound-1 exhibited potent anticancer activity with inhibitory concentration value of 17.3 μg/mL. The isolated compounds also displayed significant antioxidant potential.Conclusion: Artemisia maritima, a rich source of sesquiterpene lactone which may be responsible for significant anticancer potential and it also possess remarkable antioxidant activity and hence may be of immense importance to food Chemistry

Watershed Based Drainage Morphometric Analysis of Lidder Catchment in Kashmir Valley Using Geographical Information System

The quantitative analysis of drainage system is an important aspect of characterization of watersheds. Using watershed as a basic unit in morphometric analysis is the most logical choice because all hydrologic and geomorphic processes occur within the watershed. Lidder catchment which constitutes a segment of the western Himalayas with an area of 1159.38 km2 (10% of the river Jhelum catchment) has been selected as the study area. Various linear and areal aspects of the catchment were computed at watershed level. This was achieved using GIS to provide digital data that can be manipulated for different calculations. The analysis has revealed that the total number as well as total length of stream segments is maximum in first order streams and decreases as the stream order increases. Horton’s laws of stream numbers and stream lengths also hold good. The bifurcation ratio between different successive orders is almost constant. The drainage density values of the different watersheds exhibit high degree of positive correlation (0.97) with the stream frequency suggesting that there is an increase in stream population with respect to increasing drainage density and vice versa

Air layering in nutmeg (Myristica fragrans Houtt.)

Nutmeg is an important perennial spice crop, which is dioecious in nature. Vegetative propagation is the norm in commercial propagation of the tree. The existing practice of propagation is grafting and budding which needs good skill and expertise for reasonable success. As an alternative to these two methods, air layering was attempted in matured trees for the first time in the country. Air layering was successful in plagiotropic and orthotropic shoots with 100 per cent survival. This method is cost effective and is easy for adoption

Investigation of puffing and micro-explosion of water-in-diesel emulsion spray using shadow imaging

Water-in-diesel emulsions potentially favor the occurrence of micro-explosions when exposed to elevated temperatures, thereby improving the mixing of fuels with the ambient gas. The distributions and sizes of both spray and dispersed water droplets have a significant effect on puffing and micro-explosion behavior. Although the injection pressure is likely to alter the properties of emulsions, this effect on the spray flow puffing and micro-explosion has not been reported. To investigate this, we injected a fuel spray using a microsyringe needle into a high-temperature environment to investigate the droplets’ behavior. Injection pressures were varied at 10% v/v water content, the samples were imaged using a digital microscope, and the dispersed droplet size distributions were extracted using a purpose-built image processing algorithm. A high-speed camera coupled with a long-distance microscope objective was then used to capture the emulsion spray droplets. Our measurements indicated that the secondary atomization was significantly affected by the injection pressure which reduced the dispersed droplet size and hence caused a delay in puffing. At high injection pressure (500, 1000, and 1500 bar), the water was evaporated during the spray and although there was not enough droplet residence time, puffing and micro-explosion were clearly observed. This study suggests that high injection pressures have a detrimental effect on the secondary atomization of water-in-diesel emulsions

Chemokine-cytokine networks in the head and neck tumor microenvironment

Head and neck squamous cell carcinomas (HNSCCs) are aggressive diseases with a dismal patient prognosis. Despite significant advances in treatment modalities, the five-year survival rate in patients with HNSCC has improved marginally and therefore warrants a comprehensive understanding of the HNSCC biology. Alterations in the cellular and non-cellular components of the HNSCC tumor micro-environment (TME) play a critical role in regulating many hallmarks of cancer development including evasion of apoptosis, activation of invasion, metastasis, angiogenesis, response to therapy, immune escape mechanisms, deregulation of energetics, and therefore the development of an overall aggressive HNSCC phenotype. Cytokines and chemokines are small secretory proteins produced by neoplastic or stromal cells, controlling complex and dynamic cell–cell interactions in the TME to regulate many cancer hallmarks. This review summarizes the current understanding of the complex cytokine/chemokine networks in the HNSCC TME, their role in activating diverse signaling pathways and promoting tumor progression, metastasis, and therapeutic resistance development.This study was supported by Ramalingaswami Fellowship (Grant number: D.O.NO.BT/HRD/35/02/2006) from the Department of Biotechnology, Govt. of India, New Delhi to Muzafar A. Macha. Sidra Medicine Precision Program funded this research to Mohammad Haris (5081012001, 5081012001) and Ajaz A. Bhat (5081012003)

Tumor Microenvironment: An Evil Nexus Promoting Aggressive Head and Neck Squamous Cell Carcinoma and Avenue for Targeted Therapy

Head and neck squamous cell carcinoma (HNSCC) is a very aggressive disease with a poor prognosis for advanced-stage tumors. Recent clinical, genomic, and cellular studies have revealed the highly heterogeneous and immunosuppressive nature of HNSCC. Despite significant advances in multimodal therapeutic interventions, failure to cure and recurrence are common and account for most deaths. It is becoming increasingly apparent that tumor microenvironment (TME) plays a critical role in HNSCC tumorigenesis, promotes the evolution of aggressive tumors and resistance to therapy, and thereby adversely affects the prognosis. A complete understanding of the TME factors, together with the highly complex tumor-stromal interactions, can lead to new therapeutic interventions in HNSCC. Interestingly, different molecular and immune landscapes between HPV+ve and HPV-ve (human papillomavirus) HNSCC tumors offer new opportunities for developing individualized, targeted chemoimmunotherapy (CIT) regimen. This review highlights the current understanding of the complexity between HPV+ve and HPV-ve HNSCC TME and various tumor-stromal cross-talk modulating processes, including epithelial-mesenchymal transition (EMT), anoikis resistance, angiogenesis, immune surveillance, metastatic niche, therapeutic resistance, and development of an aggressive tumor phenotype. Furthermore, we summarize the recent developments and the rationale behind CIT strategies and their clinical applications in HPV+ve and HPV-ve HNSCC