Alleviating cancer drug toxicity by inhibiting a bacterial enzyme

The dose-limiting side effect of the common colon cancer chemotherapeutic CPT-11 is severe diarrhea caused by symbiotic bacterial β-glucuronidases that reactivate the drug in the gut. We sought to target these enzymes without killing the commensal bacteria essential for human health. Potent bacterial β-glucuronidase inhibitors were identified by high-throughput screening and shown to have no effect on the orthologous mammalian enzyme. Crystal structures established that selectivity was based on a loop unique to bacterial β-glucuronidases. Inhibitors were highly effective against the enzyme target in living aerobic and anaerobic bacteria, but did not kill the bacteria or harm mammalian cells. Finally, oral administration of an inhibitor protected mice from CPT-11-induced toxicity. Thus, drugs may be designed to inhibit undesirable enzyme activities in essential microbial symbiotes to enhance chemotherapeutic efficacy.     

The management of bovine fractures: a review of 59 cases

Current trends in bovine fracture repair are reviewed with reference to 59 cases. Thirty-one cases were managed surgically, 14 by external fixation, and six by stall confinement. Eight animals were slaughtered without treatment being attempted. A successful outcome was achieved in 90 per cent of the surgically treated cases, compared with 57 per cent for those treated by external fixation methods.     

Efficacy of doramectin against natural and experimental infections of Lernaea cyprinacea in carps

Efficacy of doramectin administered via oral and parenteral routes against experimentally induced and natural infections of the copepod parasite Lernaea cyprinacea in carps was studied. Administration of doramectin incorporated in feed at 1mg/kg b.wt. of fish for 10 days effectively controlled experimentally induced Lernaea infection in Labeo fimbriatus fingerlings within an average of 19 days of post-treatment as compared to the normal course of 41 days. Similarly, doramectin given through feed at 1mg/kgb.wt. of fish for 10 days was equally effective in controlling natural infection of this parasite in the underyearlings of Catla catla and L. fimbriatus. Intramuscular administration of doramectin at 200mug/kgb.wt. of fish effectively removed adult Lernaea infection in L. fimbriatus as early as 18 days of treatment as compared to the time period of 43 days taken by the untreated fish to get rid of the infection. Single intramuscular administration of the drug was more effective against the parasite than its administration in multiple divided doses. In all cases, doramectin did not cause any noticeable adverse reactions or toxicity to the fish host. In view of the handling associated stress and other operational difficulties involved, a single intramuscular administration of the drug at 200mug/kgb.wt. is suggested for treatment of heavily infected adults and brood stock of carps. Doramectin incorporated in feed at 1mg/kgb.wt. of fish is best suited for treatment of Lernaea infection in young fish including fingerlings. However, detailed studies on the toxicity and pharmacokinetics of doramectin upon its administration to aquatic organisms and the environmental impact of its usage are required to be undertaken before finally recommending the safe use of this drug for control of parasitic infections of aquatic organisms.     

Induction of triploidy and tetraploidy in stinging catfish, Heteropneustes fossilis (Bloch), using heat shock

Induction of triploidy and tetraploidy was attempted in Heteropneustes fossilis using heat shock. The optimal age of zygote, temperature level and duration of thermal shock required for effective induction of triploidy and tetraploidy was investigated in a series of experiments. A maximum of 82±7% triploids (3n=87) were obtained when fertilized eggs (2.5‐min old) were heat shocked at 40°C for 4‐min duration. A maximum of 40±8% tetraploids (4n=116) was obtained when the fertilized eggs (30‐min old) were heat shocked at 40°C for 4‐min duration. The triploid and tetraploid red blood cells (RBCs) nucleus volumes were 1.4 and 2.1 times greater, respectively, than that of the diploid RBC nucleus.     

A mid–late Holocene flood record from the alluvial reach of the Mahi River, Western India

Flooding of rivers in India is linked with the peak monsoons. Investigating the linkage between monsoonal patterns and flood history of various rivers is therefore of fundamental importance in the Indian context. In the present study, the slackwater deposits in the alluvial reaches of the Mahi river basin, western India have been documented. These occur in the ravines incised during the early Holocene on an alluvial surface comprising sediments of Late Pleistocene age. The slackwater deposits occur at elevations up to 20 m from the present river level and extend to about 500 m inland. The carbonate rich sediments forming the ravine cliffs have provided bank stability and the dissections in the ravines have helped in the accumulation of slackwater deposits due to backflooding of the floodwater from the main channel. Recent gullies have incised the sediments and exposed deposits related to major flood events. The best exposures of slackwater deposits have been observed at Dodka. The sediment succession of the slackwater deposits is dominated by bedsets and laminasets of silt and sand separated by colluvial sediments. Four events of flood deposition occurred during the mid to late Holocene. Two units of slackwater deposits, SWD 2 and 4 have been dated by IRSL at 4.6 ± 1 ka and 1.7 ± 0.5 ka. The stratigraphy of these deposits indicates that the first two slackwater units (SWD1 and SWD2) have resulted due to flooding in a regime of intense monsoon. The other two units, however, represent extreme high magnitude floods in a period of low average precipitation.     

Effect of conservation agriculture on stratification of soil organic matter under cereal-based cropping systems

ABSTRACT

Degradation of soil quality caused by conventional tillage practices is a major concern for the sustainability of rice-wheat cropping systems in South Asian region. Therefore, suitable conservation agriculture (CA) practices are required. This study investigates the stratification and storage of soil organic carbon (SOC) and total nitrogen (TN) as affected by eight years of different CA practices in the North-West Indo-Gangetic Plains of India. There were four treatments: (1) conventionally tilled rice-wheat cropping system, (2) reduced-till CA-based rice-wheat-mungbean system, (3) no-till CA-based rice-wheat-mungbean system, and (4) no-till CA-based maize-wheat-mungbean system. The mean stratification ratio (SR) (i.e. a ratio of the concentrations of SOC and TN in the soil surface to those in a deeper layer) of SOC and TN for 0–5:5–10, 10–15, 15–20, 20–25 and 25–30 cm were found higher (> 2) under CA practices compared to intensive tillage-based conventional agricultural practice (< 2). No-till CA-based rice-wheat-mungbean system stored the highest amount of SOC (25.32 Mg ha^?1) whereas reduced till CA-based rice-wheat-mungbean system stored highest amount of TN (3.21 Mg ha^?1) at 0–30 cm soil depth. This study shows that CA stratifies SOC and TN and helps to enhance SOC sequestration and soil quality.     

Effect of dietary resveratrol in ameliorating aflatoxin B1‐induced changes in broiler birds

Consumption of aflatoxin B1 (AFB1) contaminated feed by poultry affects the health of broiler birds causing severe economic losses. The use of phytochemicals is a safe, effective, alternative and practical approach to combat the toxic effect of AF in broilers. Resveratrol, a polyphenol derived from red grapes, berries and peanuts, exerts anti‐inflammatory, antioxidant and immunomodulatory effects. Our study was aimed at evaluating the possible protective effects of resveratrol against the adverse effects of AFB1 in broiler birds. A feeding trial of 42 days of duration was undertaken in a completely randomized design with five dietary treatments: G1‐AFB1(1.0 ppm); G2‐CTR (basal diet alone); G3‐AFB1(1.0 ppm)+Resv 0.5%; G4‐AFB1(1.0 ppm)+Resv 1%; and G5‐Resv 1%. Gain in body weight (BWG) and feed intake (FI) was observed to be highest (p < 0.05) in the AFB1 birds followed by the control group. Feed conversion ratio was lowest in G2‐CTR birds and failed to record any significant variation (p > 0.05) between groups as well as within groups. Birds fed resveratrol at both 0.5% and 1.0% levels in combination with AFB1 as well as alone along with basal diet had lower BWG and FI between the fourth and fifth week and also at the fifth week (p < 0.05). No variation (p > 0.05) was obtained in the FCR of AFB1 and resveratrol group of broiler birds. AFB1 feeding significantly increased the activities of aspartate‐(AST) and alanine‐(ALT) amino transferase, superoxide dismutase (SOD) and catalase (CAT) activities (p < 0.05) but lowered glucose, cholesterol and triglyceride levels in serum. Supplementation of resveratrol helped in increasing the activities of the oxidative enzymes and in improving the plasma total antioxidant capacity (TAOC) and total protein (TP) significantly (p < 0.05) and protein values. The livers of AFB1 group showed degeneration of hepatocytes, bile duct hyperplasia and microgranuloma formation. In resveratrol supplemented birds, the severity and degree of the liver lesions was far less. Apoptotic proteins failed to show any variation in expression between AFB1, control and resveratrol group of birds. The inclusion of resveratrol in broiler diets enhanced antioxidant status of birds indicating the protective effect of resveratrol against AFB1‐induced toxicity. So, we advice use of resveratrol as a feed additive to control aflatoxicosis in poultry farms.