Role of cAMP Homeostasis in Intra-Macrophage Survival and Infectivity of Unicellular Parasites like <em>Leishmania</em>

Unicellular eukaryotic pathogen Leishmania donovani, an intra-macrophage protozoan parasite, on exposure to phagolysosome conditions (PC) of mammalian macrophages, show increased cAMP level and cAMP-dependent protein kinase A (PKA) resulting in resistance to macrophage oxidative burst. In order to have a comprehensive understanding of cAMP signaling and their contribution to infectivity, studies were carried out on all the enzymes associated with cAMP metabolism such as adenylate cyclase, phosphodiesterase, pyrophosphatase and the regulatory and catalytic subunits of PKA. This chapter deals in detail the contribution of these components of cAMP signaling in cAMP homeostasis of the parasite as well as their role on successful host-parasite interaction leading to intracellular parasite survival and establishment of infection. Finally, a discussion is made about how these observations might be exploited for developing drug candidates targeting parasite specific features

Where do free-ranging dogs rest? A population level study reveals hidden patterns in resting site choice

Free-ranging dogs (FRDs) in human-dominated areas encounter obstacles such as noise, pollution, limited food sources, and anthropogenic disturbance while resting. Since FRDs have survived as a population in India, as in many other parts of the Global South for centuries, they provide a unique opportunity to study adaptation of animals to the human-dominated urban landscape. We documented factors impacting resting behaviour and site preferences in three states of India, for 284 dogs, leading to 6047 observations over 3 years. 7 physical parameters of the resting sites, along with the biological factors like mating and pup-rearing and time of day affected their choice of resting sites. The frequency-rank distribution of the unique combinations in which the parameters were selected followed a Power law distribution, which suggests underlying biological reasons for the observed preferences. Further, 3 of these parameters showed maximum consistency of choice in terms of the sub-parameters selected, explaining 30% of the observations. FRDs prefer to rest close to their resource sites within the territory, at a place that enabled maximum visibility of the surroundings. They chose such sites in the core of the territory for sleeping. At other times, they chose such sites away from the core, and were less restive, thus allowing for immediate response in case of intrusion or threat. They generally avoided anthropogenic disturbance for sleeping, and preferred areas with shade.Incorporating these aspects into urban management plans can promote human-dog cooperation and reduce situations of conflict. We envisage more inclusive urban areas in the future, that can allow for co-existence of the humans and their oldest companions in the commensal relationship that has been maintained for hundreds of generations of dogs in this part of the world.Comment: 2 figures, 2 tables, ES

Sarcomatous transformation of florid cemento-osseous dysplasia: a case report

Florid cemento-osseous dysplasia (COD) represents a rare group of benign fibro-osseous disorders, while osteogenic sarcoma (OS) on the other hand, is a malignant tumour of ominous prognosis. The malignant transformation of a benign fibro-osseous lesion of the jaw is quite uncommon and has few reported cases. The clinico-radiological findings and histopathological analysis of a lesion present in all four quadrants of the jaw of a patient who reported at the outpatient department of a regional dental college is presented here. The lesion underwent sarcomatous transformation over two months and the findings were confirmed by histopathological evaluation. Although florid cemento-osseous dysplasia is a benign lesion of the jaw with a very low propensity for malignant transformation, it should be closely monitored in patients with tumour predisposition syndromes. Further research and molecular studies are required for better understanding of inadvertent changes

Comparative evaluation of dental computed tomographic software program in the analysis of jaw lesions in comparison with panoramic radiographs

Background: Dental radiology has long played an exciting and critical diagnostic role in dentistry. The development of novel imaging modalities like computed tomography (CT) and magnetic resonance imaging (MRI) has revolutionized dental and medical diagnosis. However the role of conventional radiography in dentistry remains unparalleled. The current study was undertaken to evaluate the effectiveness of dental CT software compared to panoramic radiography in evaluation of the jaw lesions.Methods: Twenty cases of maxillary and mandibular jaw lesions were examined radiographically by digital panoramic radiography orthopantomography (OPG) and dental CT software. The radiographic images obtained with these two examination modalities were compared for visualization of antero-posterior extent of the lesion, dimension of the lesion, cortical bone involvement, tooth displacement, root resorption, involvement of the maxillary sinus, delineation of the neurovascular canal, presence or absence of calcification, imaging diagnosis of the lesion (cystic/solid).Results: The dental CT program rated significantly (P<0.001) higher in all points examined than the panoramic radiography. The dental CT program was found to be superior for detecting cortical bone involvement (P<0.02) and delineation of the mandibular canal (P<0.02) to the conventional CT program.Conclusions: Dentascan offers better characterization of the pathologic processes due to its ability to differentiate between different tissue types based on their Hounsfield units. Hence it can define the contents of the pathology as cystic or solid and thus predict the diagnosis of the lesion

18β-glycyrrhetinic acid triggers curative Th1 response and nitric oxide up-regulation in experimental visceral leishmaniasis associated with the activation of NF-κB

The efficacy of 18&#946;-glycyrrhetinic acid (GRA), a pentacyclic triterpene belonging to the &#946;-amyrin series of plant origin, was evaluated in experimental visceral leishmaniasis. GRA is reported to have antitumor and immunoregulatory activities, which may be attributable in part to the induction of NO. Indeed, an 11-fold increase in NO production was observed with 20 &#181;M GRA in mouse peritoneal macrophages infected with Leishmania donovani promastigotes. In addition to having appreciable inhibitory effects on amastigote multiplication within macrophages (IC50, 4.6 &#181;g/ml), complete elimination of liver and spleen parasite burden was achieved by GRA at a dose of 50 mg/kg/day, given three times, 5 days apart, in a 45-day mouse model of visceral leishmaniasis. GRA treatment resulted in reduced levels of IL-10 and IL-4, but increased levels of IL-12, IFN-&#947;, TNF-&#945;, and inducible NO synthase, reflecting a switch of CD4+ differentiation from Th2 to Th1. This treatment is likely to activate immunity, thereby imparting resistance to reinfection. GRA induced NF-&#954;B migration into the nucleus of parasite-infected cells and caused a diminishing presence of I&#954;B in the cytoplasm. The lower level of cytoplasmic I&#954;B&#945; in GRA-treated cells resulted from increased phosphorylation of I&#954;B&#945; and higher activity of I&#954;B kinase (IKK). Additional experiments demonstrated that GRA does not directly affect IKK activity. These results suggest that GRA exerts its effects at some level upstream of IKK in the signaling pathway and induces the production of proinflammatory mediators through a mechanism that, at least in part, involves induction of NF-&#954;B activation

Aggressive salivary duct carcinoma with widespread dissemination: a case report

Salivary duct carcinoma is a rare and aggressive salivary gland malignancy with a poor prognosis. Due to the paucity of literature, very little is known about this neoplasm. We have described such a case in this case report and highlighted the clinical and histopathological features associated with this disease. A sixty-year old male patient reported in the outpatient department of a regional dental college and hospital with a circular firm growth in the mandibular anterior region and mobility of adjacent mandibular teeth. An array of investigations including radiographic, tomographic, ultrasonographic as well as histopathological were performed. It was diagnosed as invasive salivary duct carcinoma with distant metastases in the shoulder joint, ribs as well as pelvic bones. Currently, no National Comprehensive Cancer Network guidelines for the specific treatment of salivary duct carcinomas exist. National Comprehensive Cancer Network guidelines recommend complete surgical excision of tumors for major salivary gland tumors without nodal involvement (N0) with or without neck dissection for high-grade and T3/T4 salivary gland tumors.

Granulomatosis with polyangiitis

Granulomatosis with polyangiitis is a small and medium vessel vasculitis. It may affect any organ system. Neurological involvement, though less frequent, mostly manifests as peripheral neuropathy. Central nervous system (CNS) involvement as autoimmune cerebritis is rare but may be devastating. We report a patient having CNS involvement in the form of Parkinsonism long before the development of typical upper and lower airway symptoms. Granulomatosis with polyangiitis was diagnosed on the basis of cavitary lung lesions along with epistaxis, granulomatous inflammation from fine needle aspiration (FNAC) of lymph node and high titer of c-ANCA. The patient was commenced on intravenous methylprednisolone followed by mycophenolate mofetil and responded to treatment. Autoimmune cerebritis may present with subacute manifestation of diffuse CNS involvement

Granulomatosis with polyangiitis

Granulomatosis with polyangiitis is a small and medium vessel vasculitis. It may affect any organ system. Neurological involvement, though less frequent, mostly manifests as peripheral neuropathy. Central nervous system (CNS) involvement as autoimmune cerebritis is rare but may be devastating. We report a patient having CNS involvement in the form of Parkinsonism long before the development of typical upper and lower airway symptoms. Granulomatosis with polyangiitis was diagnosed on the basis of cavitary lung lesions along with epistaxis, granulomatous inflammation from fine needle aspiration (FNAC) of lymph node and high titer of c-ANCA. The patient was commenced on intravenous methylprednisolone followed by mycophenolate mofetil and responded to treatment. Autoimmune cerebritis may present with subacute manifestation of diffuse CNS involvement

Building sustainable digital communities: A five-pronged social-informatics research approach in Bangladesh

In a developing society, critical issues highlighted are not just about the technology, but with social factors such as culture, institutions, organizational issues, and individual identities. Understanding such factors is significant to illustrate how best to create sustainable communities using technology. Researchers at Monash University have collaborated with Oxfam International and developed a 5-year international development project known as PROTIC. This paper aims to give readers an overview of the PROTIC project and describe how the five doctoral research students are designing their research to achieve a common goal of developing sustainable digital communities in Bangladesh. The students follow different research methods in their respective projects, targeting overall long-term sustainability for the vulnerable communities identified in each of their studies. Although using five distinct research project approaches, the PROTIC project aims to use the exploratory study to make information and communication technologies (ICT) more sustainable for underserved communities. The findings from these researchers will impact on design and implementation of ICT-based socio-economic development projects undertaken by international development organizations