Ever since their discovery about 60 years ago as therapeutic agent for visceral leishmaniasis (VL) or kala-azar, pentavalent antimonials (Sbv) have remained the first line treatment of choice all over the world including India. But recently, the number of kala-azar patients unresponsive to sodium stibogluconate (SSG) therapy, is steadily increasing in India. In this study, three clinical isolates, of which two were from SSG unresponsive and one from SSG responsive patients were evaluated for their infectivity and for their chemotherapeutic responses in vitro (macrophage–amastigote system) and in vivo (in hamsters). Persistence of SSG resistance was also checked by repeated passages in vitro as well as in vivo. The drug resistant strains (2039 and 2041) did not respond to SSG therapy both in vitro as well as in vivo but strains 2001 and Dd8 showed full sensitivity to SSG treatment. All the four strains responded well to amphotericin B and miltefosine treatment both in macrophages and in hamsters. The specific chemotherapeutic responses of all the strains to SSG were consistently persistent after repeated passages in cultures and in vivo, which indicates that these isolates are truly refractory to SSG treatment in field conditions. Two isolates were also transfected with green fluorescent protein (GFP) for the development of in vitro assay for studying antileishmanial activities of new and reference drugs in macrophages by flow cytometry.

Refractoriness to the treatment of sodium stibogluconate in Indian kala-azar field isolates persist in in vitro and in vivo experimental models

Effect of rainfall intensity and distribution on groundwater level fluctuations

Identification, characterization, and inhibition of Plasmodium falciparum beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ).

Hard rocks or crystalline rocks (i.e., plutonic and metamorphic rocks) constitute the basement of all continents, and are particularly exposed at the surface in the large shields of Africa, India, North and South America, Australia and Europe. They were, and are still in some cases, exposed to deep weathering processes. The storativity and hydraulic conductivity of hard rocks, and thus their groundwater resources, are controlled by these weathering processes, which created weathering profiles. Hard-rock aquifers then develop mainly within the first 100 m below ground surface, within these weathering profiles. Where partially or noneroded, these weathering profiles comprise: (1) a capacitive but generally low-permeability unconsolidated layer (the saprolite), located immediately above (2) the permeable stratiform fractured layer (SFL). The development of the SFL’s fracture network is the consequence of the stress induced by the swelling of some minerals, notably biotite. To a much lesser extent, further weathering, and thus hydraulic conductivity, also develops deeper below the SFL, at the periphery of or within preexisting geological discontinuities (joints, dykes, veins, lithological contacts, etc.). The demonstration and recognition of this conceptual model have enabled understanding of the functioning of such aquifers. Moreover, this conceptual model has facilitated a comprehensive corpus of applied methodologies in hydrogeology and geology, which are described in this review paper such as water-well siting, mapping hydrogeological potentialities from local to country scale, quantitative management, hydrodynamical modeling, protection of hard-rock groundwater resources (even in thermal and mineral aquifers), computing the drainage discharge of tunnels, quarrying, etc.

/pdf/review-hydrogeology-of-weathered-crystalline-hard-rock-51dec5u519.pdf

Review: Hydrogeology of weathered crystalline/hard-rock aquifers—guidelines for the operational survey and management of their groundwater resources

In this study, cDNA microarray analysis of a closely related species, Leishmania major, was used as a screening tool to compare antimonial-resistant and susceptible clinical isolates of Leishmania donovani in order to to identify candidate genes on the basis of antimony resistance. Clinically confirmed resistant isolate 39 and sensitive isolate 2001 were used in this study. Many differentially regulated genes were identified whose expression levels differ in sodium antimony gluconate (SAG)-treated patients. Interestingly, genes on the array, showing changes in expression of over 2-fold revealed the identity of ABC transporters, which are known determinants of drug resistance in laboratory mutants. The functionality of the transporters was validated by flow cytometry which, being biologically informative, provides direct clues to gene function. The results suggest that isolate 39 could have developed resistance by an increased multidrug resistance protein (MRP)-like pump. This study provides preliminary clues to the role of a thiol-dependent efflux system in antimonial resistant clinical isolates of Leishmania donovani.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0031182007002284

Differential gene expression analysis in antimony-unresponsive Indian kala azar (visceral leishmaniasis) clinical isolates by DNA microarray

Short-interval water level measurements using automatic water level recorder in a deep well in an unconfined crystalline rock aquifer at the campus of NGRI, near Hyderabad shows a cyclic fluctuation in the water levels. The observed values clearly show the principal trend due to rainfall recharge. Spectral analysis was carried out to evaluate correlation of the cyclic fluctuation to the synthetic earth tides as well as groundwater withdrawal time series in the surrounding. It was found that these fluctuations have considerably high correlation with earth tides whereas groundwater pumping does not show any significant correlation with water table fluctuations. It is concluded that earth tides cause the fluctuation in the water table. These fluctuations were hitherto unobserved during manual observations made over larger time intervals. It indicates that the unconfined aquifer is characterised by a low porosity.

https://hal.archives-ouvertes.fr/hal-00458315/document

Establishment of earth tides effect on water level fluctuations in an unconfined hard rock aquifer using spectral analysis

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Establishment of earth tides effect on water level fluctuations in an unconfined hard rock aquifer using spectral analysis

Establishment of earth tides effect on water level fluctuations in an unconfined hard rock aquifer using spectral analysis