Non‐immunosuppressive FTY720‐derivative OSU‐2S mediates reactive oxygen species‐mediated cytotoxicity in canine B‐cell lymphoma

OSU‐2S is a FTY720 (Fingolimod) derivative that lacks immunosuppressive properties but exhibits strong anti‐tumour activity in several haematological and solid tumour models. We have recently shown OSU‐2S to mediate potent cytotoxicity in human mantle cell lymphoma cell lines and primary cells. We report here the pre‐clinical activity of OSU‐2S in spontaneous B‐cell lymphoma of dogs which shares many characteristics of human lymphoma. OSU‐2S mediated apoptosis in canine B‐cell lines and primary B‐cell lymphoma cells obtained from spontaneous lymphoma bearing dogs. OSU‐2S induced reactive oxygen species (ROS) in canine lymphoma cells and inhibition of ROS partially rescued OSU‐2S‐mediated cell death. These studies provide a rational basis for the use of spontaneous lymphoma in pet dogs as a preclinical large animal model for the development of OSU‐2S as small molecule for treating people and dogs with lymphoma.     

Potentially Toxic Trace Metals in Water and Lake-Bed Sediment of Panchpokhari,an Alpine Lake Series in the Central Himalayan Region of Nepal

This study assessed the level of potentially toxic trace metals (PTMs), seasonal variations, and their possible sources from the surface water and lake-bed sediment of Panchpokhari lake series, an alpine and glacial lake at 4160 m a.s.l. in Central Nepal. The lake series have five lakes, with Lake-1 larger than others. So, Lake-1 was investigated thoroughly during pre-monsoon and post-monsoon seasons. Sediment core was collected from the deepest basin of the Lake-1 during pre-monsoon. Most of the PTM concentrations were higher in the pre-monsoon season; however, Sc, Cr, Cu, Zn, As, and Ag were higher in the post-monsoon. This is an indication that the lake has been impacted either by natural or long-range transported atmospheric pollutants. Ti, Sb, and Ag had extremely high enrichment factor (EF) in waters, whereas Cd, Zn, and As had high EF in sediments indicating that these metals originated from anthropogenic sources. Furthermore, PTM concentrations in the sediment were in the increasing order of Hg < Cd < Ag < Mo < Sb < Sn < As < U < Sc < Co < Cs < Cu < Pb < Ni < Cr < V < Zn < Rb < Mn < Ti < Fe and showed that the upper layer (top 10 cm) of lake sediment has been receiving a higher load of PTMs in the recent period. he observed EF values also suggested that major sources of PTMs in the sediment were from crustal origin except for a few metals (Ti, V, Sb, and Ag) which were enriched anthropogenically due to long-range transport of atmospheric pollutants, deposited at the higher elevations. Nevertheless, the level of pollution in sediments was low as indicated both by EF and geo-accumulation index.     

Duck virus enteritis (duck plague) – a comprehensive update

Duck virus enteritis (DVE), also called duck plague, is one of the major contagious and fatal diseases of ducks, geese and swan. It is caused by duck enteritis virus (DEV)/Anatid herpesvirus-1 of the genus Mardivirus, family Herpesviridae, and subfamily Alpha-herpesvirinae. Of note, DVE has worldwide distribution, wherein migratory waterfowl plays a crucial role in its transmission within and between continents. Furthermore, horizontal and/ or vertical transmission plays a significant role in disease spread through oral-fecal discharges. Either of sexes from varying age groups of ducks is vulnerable to DVE. The disease is characterized by sudden death, vascular damage and subsequent internal hemorrhage, lesions in lymphoid organs, digestive mucosal eruptions, severe diarrhea and degenerative lesions in parenchymatous organs. Huge economic losses are connected with acute nature of the disease, increased morbidity and mortality (5%–100%), condemnations of carcasses, decreased egg production and hatchability. Although clinical manifestations and histopathology can provide preliminary diagnosis, the confirmatory diagnosis involves virus isolation and detection using serological and molecular tests. For prophylaxis, both live-attenuated and killed vaccines are being used in broiler and breeder ducks above 2 weeks of age. Since DEV is capable of becoming latent as well as shed intermittently, recombinant subunit and DNA vaccines either alone or in combination (polyvalent) are being targeted for its benign prevention. This review describes DEV, epidemiology, transmission, the disease (DVE), pathogenesis, and advances in diagnosis, vaccination and antiviral agents/therapies along with appropriate prevention and control strategies.     

Rabies – epidemiology,pathogenesis, public health concerns and advances in diagnosis and control: a comprehensive review

Rabies is a zoonotic, fatal and progressive neurological infection caused by rabies virus of the genus Lyssavirus and family Rhabdoviridae. It affects all warm-blooded animals and the disease is prevalent throughout the world and endemic in many countries except in Islands like Australia and Antarctica. Over 60,000 peoples die every year due to rabies, while approximately 15 million people receive rabies post-exposure prophylaxis (PEP) annually. Bite of rabid animals and saliva of infected host are mainly responsible for transmission and wildlife like raccoons, skunks, bats and foxes are main reservoirs for rabies. The incubation period is highly variable from 2 weeks to 6 years (avg. 2–3 months). Though severe neurologic signs and fatal outcome, neuropathological lesions are relatively mild. Rabies virus exploits various mechanisms to evade the host immune responses. Being a major zoonosis, precise and rapid diagnosis is important for early treatment and effective prevention and control measures. Traditional rapid Seller's staining and histopathological methods are still in use for diagnosis of rabies. Direct immunofluoroscent test (dFAT) is gold standard test and most commonly recommended for diagnosis of rabies in fresh brain tissues of dogs by both OIE and WHO. Mouse inoculation test (MIT) and polymerase chain reaction (PCR) are superior and used for routine diagnosis. Vaccination with live attenuated or inactivated viruses, DNA and recombinant vaccines can be done in endemic areas. This review describes in detail about epidemiology, transmission, pathogenesis, advances in diagnosis, vaccination and therapeutic approaches along with appropriate prevention and control strategies.     

Prevalence and pathology of dermatophilosis in camels (Camelus dromedaries) in Iran

Gross and histopathologic lesions of the integumentary system were studied in 103 camels (Camelus dromedarius) slaughtered in Yazd Province of Iran. Dermatophilosis was diagnosed in 14 (13.6%) of the studied camels. Grossly, patchy thickening of the skin with dark brown scabs or crusts were observed on the rump, flanks, abdomen, shoulders, and neck. A heavy infestation with brown hard ticks was present on the lesions in almost all of the affected camels. On parasitology examination, all the ticks were identified as Hyalomma spp. Histopathologic examination of the affected skins revealed prominent superficial thickening of the epidermis as orthokeratotic and parakeratotic hyperkeratosis, degenerating neutrophils, serous fluid, and bacterial filaments. A lot of keratinaceous debris associated with an exudate rich in neutrophils were seen as remarkable features of the lesions on the superficial epidermis. Dermal inflammation was mild with infiltration of mononuclear inflammatory cells, particularly lymphocytes, around superficial vessels. A Gram-positive filamentous organism which was divided into parallel rows of cocci was observed in the crusts by Brown and Brenn Gram stain. This is the first report of the occurrence of dermatophilosis in the camels of Iran. With regard to infestation of the lesions by Hyalomma spp., it seems that this tick may have an important role in the pathogenesis of dermatophilosis in the camels of this region.     

LRP6 mutation in a family with early coronary disease and metabolic risk factors

Coronary artery disease (CAD) is the leading cause of death worldwide and is commonly caused by a constellation of risk factors called the metabolic syndrome. We characterized a family with autosomal dominant early CAD, features of the metabolic syndrome (hyperlipidemia, hypertension, and diabetes), and osteoporosis. These traits showed genetic linkage to a short segment of chromosome 12p, in which we identified a missense mutation in LRP6, which encodes a co-receptor in the Wnt signaling pathway. The mutation, which substitutes cysteine for arginine at a highly conserved residue of an epidermal growth factor-like domain, impairs Wnt signaling in vitro. These results link a single gene defect in Wnt signaling to CAD and multiple cardiovascular risk factors.     

The effective dominance of resistance genes in relation to the evolution of resistance

Field selection for a rare insecticide resistance (R) gene can be substantially delayed if R is rendered effectively recessive [if all or most heterozygotes ( R + ) are killed by the field dosages] and if a representative sample (+ +, R +, RR) of the population is permitted to escape exposure. The relationship between heterozygote mortality and escape in influencing selection rates has been considered at various frequencies of R. The cases when mating precedes selection, and when selection precedes mating, have been calculated using computer simulations. It is concluded that when R genes are rare it is advantageous (a) to apply the highest possible doses of insecticide in such a form that all exposed insects pick up an amount sufficient to kill all or most heterozygotes, (b) to apply the insecticide to adults after they have mated, rather than to younger adults or to larvae, and (c) to ensure that the proportion of insects given the opportunity to escape contact is as high as practical considerations allow. Once resistance is obvious (when samples are brought into the laboratory for tests), the R gene frequency will have risen to a level which makes the suggested strategy no longer valuable. Alternative strategies are briefly discussed.     

Organic pesticides. XV. Synthesis and insecticidal activity of some compounds containing phosphorus and fluorine

Forty new organofluorine compounds, containing phosphorus, have been synthesised as potential pesticides. The compounds include esters of O,O-dialkyl phosphoramidic acids of the type (RO)₂P(O)NHAr; thioesters of O,O-dialkyl thiophosphoramidic acids of the type (RO)₂P(S)NHAr; esters of O,O-dialkyl phosphonic acid of the type (RO)₂P(O)Ar and esters of O,O-dialkyl thiophosphonic acid (RO)₂P(S)OAr. All the compounds have been screened for their insecticidal activity against adult cockroaches (Periplanata americana) and a few show appreciable activity.     

Effect of organic amendments on rice yield trend,phosphorus use efficiency,uptake, and apparent balance in soil under long-term rice-wheat rotation

The experiment was conducted in a 22nd cycle of rice-wheat rotation established in the eastern India with a randomized block designed with various combinations of inorganic and organic sources of nutrients like farm yard manure (FYM), paddy straw (PS), and green manure in rice crop only. Application of nitrogen, phosphorus, and potassium (NPK) and its combination with FYM, PS, and green manuring increased the grain yield of rice significantly. Rice yield declined only in control plots (?0.003 t ha^?1 year^?1), whereas positive yield trend was maintained in all the treatments. All organically amended plots showed a better uptake as well as use efficiencies of applied phosphorus (P) inputs over control. The apparent P balance showed positive value in control treatment over the years ranging from ?4.8 to 24.8 kg ha^?1 year^?1. The positive yield trend of rice was maintained due to buildup of P from various organic inputs.