Knowledge, attitudes and biosecurity practices among the small-scale dairy farmers in Sylhet district, Bangladesh.

BACKGROUND: In the context of zoonosis, Bangladesh's small-scale dairying is yet to frame satisfactory levels due to poor biosecurity practices. OBJECTIVES: This study intended to reveal the degree of knowledge, attitudes and biosecurity practices among Sylhet district, Bangladesh's small-scale dairy farmers. We also focused on the association between biosecurity practices and the incidence of non-specific enteritis in humans. METHODS: A questionnaire-based survey was conducted on the farmers' KAP via personal interviews of 15 farmers from the randomly selected fifteen small-scale dairy farms. The questionnaire was developed with 6 questions for knowledge, 6 questions for attitude and 12 questions for the practice of biosecurity measures. Alongside that, data on the number of non-specific enteritis cases experienced by the farmers or their family members were also recorded. Spearman correlation was used to find out the correlation among KAP variables and between practice scores and non-specific enteritis incidences. RESULTS: We found an insignificant (p > 0.05) influence of demographic characteristics over knowledge, attitude and biosecurity practices. Significant (p < 0.05) and strong correlations were found in knowledge-attitude (r = 0.65), knowledge-practice (r = 0.71) and attitude-practice (r = 0.64). Incidences of non-specific enteritis and biosecurity measures' practice were also strongly correlated (r = -0.9232) and statistically significant (p < 0.05). CONCLUSIONS: Our study suggests that increasing knowledge and developing a good attitude are necessary to increase the adaptation of biosecurity measures as three of these factors are correlated. Moreover, farm biosecurity measures are closely related to human health.

Characterization of potent and selective iodonium-class inhibitors of NADPH oxidases.

The NADPH oxidases (NOXs) play a recognized role in the development and progression of inflammation-associated disorders, as well as cancer. To date, several NOX inhibitors have been developed, through either high throughput screening or targeted disruption of NOX interaction partners, although only a few have reached clinical trials. To improve the efficacy and bioavailability of the iodonium class NOX inhibitor diphenylene iodonium (DPI), we synthesized 36 analogs of DPI, focusing on improved solubility and functionalization. The inhibitory activity of the analogs was interrogated through cell viability and clonogenic studies with a colon cancer cell line (HT-29) that depends on NOX for its proliferative potential. Lack of altered cellular respiration at relevant iodonium analog concentrations was also demonstrated. Additionally, inhibition of ROS generation was evaluated with a luminescence assay for superoxide, or by Amplex Red® assay for H2O2 production, in cell models expressing specific NOX isoforms. DPI and four analogs (NSCs 740104, 751140, 734428, 737392) strongly inhibited HT-29 cell growth and ROS production with nanomolar potency in a concentration-dependent manner. NSC 737392 and 734428, which both feature nitro functional groups at the meta position, had >10-fold higher activity against ROS production by cells that overexpress dual oxidase 2 (DUOX2) than the other compounds examined (IC50≈200-400nM). Based on these results, we synthesized and tested NSC 780521 with optimized potency against DUOX2. Iodonium analogs with anticancer activity, including the first generation of targeted agents with improved specificity against DUOX2, may provide a novel therapeutic approach to NOX-driven tumors.

Synthesis of gemcitabine triphosphate (dFdCTP) as a tris(triethylammonium) salt.

First synthesis of gemcitabine triphosphate (dFdCTP) as a tris(triethylammonium) salt is reported.

A bifunctional colchicinoid that binds to the androgen receptor.

Castrate-resistant prostate cancer (CRPC) continues to be dependent on the androgen receptor (AR) for disease progression. We have synthesized and evaluated a novel compound that is a conjugate of colchicine and an AR antagonist (cyanonilutamide) designed to inhibit AR function in CRPC. A problem in multifunctional AR-binding compounds is steric hindrance of binding to the embedded hydrophobic AR ligand-binding pocket. Despite the bulky side chain projecting off of the AR-binding moiety, this novel conjugate of colchicine and cyanonilutamide binds to AR with a K(i) of 449 nmol/L. Structural modeling of this compound in the AR ligand-binding domain using a combination of rational docking, molecular dynamics, and steered molecular dynamics simulations reveals a basis for how this compound, which has a rigid alkyne linker, is able to bind to AR. Surprisingly, we found that this compound also binds to tubulin and inhibits tubulin function to a greater degree than colchicine itself. The tubulin-inhibiting activity of this compound increases cytoplasmic AR levels in prostate cancer cells. Finally, we found that this compound has greater toxicity against androgen-independent prostate cancer cells than the combination of colchicine and nilutamide. Together, these data point to several ways of inhibiting AR function in CRPC.