Association of TNF-α, IL-10 and IL-6 promoter polymorphisms in pulmonary tuberculosis patients and their household contacts of younger age group

Single nucleotide polymorphisms (SNPs) of cytokine genes have been found to be involved in the clinical outcome of Tuberculosis. The present study was aimed to identify the high risk genotypes in Tuberculosis patients and their household contacts. A total of 490 subjects were studied which includes 150 active pulmonary tuberculosis patients (APTB), 190 household contacts (HHC) and 150 healthy controls (HC). The SNPs of TNF-α (-308A/G), IL-10(-1082G/A) and IL-6(-174G/C) were performed by ARMs PCR. The IL-10 GA genotype showed significant association in APTB and HHC and was 2.3 times higher risk in APTB and 3.7 times in HHC compared to HCs. The A allele was found to be significantly associated with the risk of disease. The CC genotype of IL-6 was found to be significantly associated in APTB and an insignificant positive association in HHCs. The multifactor dimensionality reduction (MDR) analysis indicated that the genotypes of IL-6 were showing high risk with GA genotype of IL-10. In conclusion the gene interaction may be useful for identification of genotypes as biomarkers to distinguish high risk individuals.     

Role of integrons in the proliferation of multiple drug resistance in selected bacteria occurring in poultry production

ABSTRACT

• 1. The increase in microbial resistance, and in particular multiple drug resistance (MDR), is an increasing threat to public health. The uncontrolled use of antibiotics and antibacterial chemotherapeutics in the poultry industry, especially in concentrations too low to cause inhibition, and the occurrence of residues in feed and in the environment play a significant role in the development of resistance among zoonotic food-borne microorganisms.

• 2. Determining the presence and transmission methods of resistance in bacteria is crucial for tracking and preventing antibiotic resistance. Horizontal transfer of genetic elements responsible for drug resistance is considered to be the main mechanism for the spread of antibiotic resistance.

• 3. Of the many well-known genetic elements responsible for horizontal gene transfer, integrons are among the most important factors contributing to multiple drug resistance. The mechanism of bacterial drug resistance acquisition through integrons is one of the essential elements of MDR prevention in animal production.

     

Modification of Marine Natural Product Ningalin B and SAR Study Lead to Potent P-Glycoprotein Inhibitors

In this study, new marine ningalin B analogues containing a piperazine or a benzoloxy group at ring C have been synthesized and evaluated on their P-gp modulating activity in human breast cancer and leukemia cell lines. Their structure-activity relationship was preliminarily studied. Compounds 19 and 20 are potent P-gp inhibitors. These two synthetic analogues of permethyl ningalin B may be potentially used as effective modulators of P-gp-mediated drug resistance in cancer cells.     

Pet birds as potential reservoirs of virulent and antibiotic resistant zoonotic bacteria

Bacterial pathogens carried by pet birds are considered a risk for birds, workers, and pet owners. This study investigated the potential of pet birds as reservoirs for virulent multidrug-resistant (MDR) zoonotic bacteria and assessed the genetic relatedness and diversity of bacterial isolates from pet birds and human contacts. Cloacal and tracheal swabs from 125 pet birds and 70 hand swabs from human contacts were collected. The results revealed that the pet birds were reservoirs for Escherichia coli, Klebsiella pneumoniae (17.6 %, each), and Staphylococcus aureus (15.2 %). These isolates were also identified in their human contacts, at percentages of 14.3 %, 12.9 %, and 24.3 %, respectively. Virulence associated genes were identified from E. coli (stx2, stx2f, eaeA, and hlyA), K. pneumoniae (fimH, TraT, and magA), and S. aureus (PVL, hly, sea, sed genes) isolates. Multidrug-resistant E. coli, K. pneumoniae, and S. aureus were highly prevalent (81.3 %, 90.3 %, and 61.1 %, respectively). The genetic relationship between the E. coli and K. pneumoniae isolates from the pet birds and human contacts were determined by ERIC-PCR, while, RAPD-PCR was used for the S. aureus isolates. ERIC-PCR was found to have the highest discriminatory power. The clustering of the isolates from the pet birds and human contacts indicated potential transmission between the birds and workers. In conclusion, pet birds could act as potential reservoirs for zoonotic bacterial pathogens; thus, posing a risk to their human contacts.     

ABCB1-1Δ Polymorphism Can Predict Hematologic Toxicity in Dogs Treated with Vincristine

Background: Dogs that harbor the naturally occurring ABCB1-1Δ polymorphism experience increased susceptibility to avermectin-induced neurological toxicosis as a result of deficient P-glycoprotein function. Whether or not the ABCB1-1Δ polymorphism affects susceptibility to toxicity of other P-glycoprotein substrate drugs has not been studied.
Hypothesis: Dogs that possess the ABCB1-1Δ mutation are more likely to develop hematologic toxicity associated with vincristine than ABCB1 wild-type dogs.
Animals: Thirty-four dogs diagnosed with lymphoma were included in this study.
Methods: Cheek swab samples were obtained from dogs diagnosed with lymphoma that were to be treated with vincristine. DNA was extracted from cheek swabs and the ABCB1 genotype was determined. Hematologic adverse drug reactions were recorded for each dog and graded according to the Veterinary Comparative Oncology Group's criteria for adverse event reporting (Consensus Document). In order to avoid possible bias, ABCB1 genotype results for a particular patient were not disclosed to oncologists until an initial adverse event report had been submitted.
Results: Dogs heterozygous or homozygous for the ABCB1-1Δ mutation were significantly more likely to develop hematologic toxicity, specifically neutropenia ( P = .0005) and thrombocytopenia ( P = .0001), after treatment with vincristine than ABCB1 wild-type dogs.
Conclusions and Clinical Implications: At currently recommended dosages (0.5–0.7 mg/M²), vincristine is likely to cause hematologic toxicity in dogs with the ABCB1-1Δ mutation, resulting in treatment delays and unacceptable morbidity and mortality. Assessing the ABCB1-1Δ genotype before vincristine administration and decreasing the dosage may prevent toxicity and treatment delays resulting from neutropenia or thrombocytopenia.     

Prevalence of Multi-Drug-Resistant Salmonella in Equids Maintained by Low Income Individuals and on Designated Equine Farms in India

We examined 872 equids (445 maintained by low-income individuals and 427 maintained on nine designated equine farms) and, using previously described methods for bacteria, isolated Salmonella from fecal samples of 59 (6.77%) animals. Of the 646 horses, 183 donkeys, and 43 mules that had feces cultured for Salmonella, 42 (6.5%), 7 (3.8%), and 10 (23.3%), respectively, were excreting Salmonella strains in feces. Six horse mares were excreting Salmonella enterica of two different serovars simultaneously. A total of 65 Salmonella enterica isolates belonged to 13 serovars, namely S. paratyphi B var Java (14), S. I. 4, 5, 12, 27: r, i: 1, 5 (11), S. Drogana (8), S. Newport (7), S. Saintpaul (5), S. Lagos (4), S. Typhimurium (5), S. Kottbus (3), S. Bovismorbificans (3), S. Dumfries (2), S. Tshiongwe (1) S. Weltevreden (monophasic) (1), and S. enterica ssp salamae (1). With Salmonella-specific polymerase chain reaction (PCR) using hisJ gene primers, 107 (12.3) fecal samples yielded a specific amplicon of 496 bp. On using PCR, prevalence of Salmonella in donkeys, horses, and mules was 4.9%, 10.8%, and 65.1%, respectively. With both methods of Salmonella detection in feces, prevalence was significantly higher in female than in male donkeys and horses. Salmonella shedding in feces was significantly higher in equids maintained by low-income people than those at designated equine farms. Almost all Salmonella isolates (63 of 65) had multiple-drug-resistance (MDR, resistance to three or more drugs). Salmonella isolates were commonly resistant to sulfamethoxazole (90.8%), tetracycline (70.8%), doxycycline (67.7%), furazolidone (66.2%), and colistin (55.4%). A few isolates had resistance to trimethoprim (3.1%), ciprofloxacin (3.1%), ceftriaxone (3.1%), ceftazidime (3.1%), cefoperazone (3.1%), chloramphenicol (4.6%), cefotaxime (6.2%), gentamicin (9.2%), ampicillin + cloxacillin (9.2%), cotrimoxazole (13.8%), kanamycin (13.8%), amoxicillin + clavulanic acid (16.9%), imipenem (16.9%), ampicillin (18.5%), amikacin (23.1%), neomycin (27.7%), nalidixic acid (33.8%), and streptomycin (36.9%). With the exception of 13 Salmonella isolates of S. Drogana (4), S. Newport (4), S. I. 4, 5, 12, 27: r, i: 1, 5 (4) and S. Kottbus (1) serovars, all had one or more than one plasmid. Molecular weight of plasmids ranged between 3 kDa and >87 kDa. One heavy plasmid (≥87 kda) was present in all the 52 plasmid-positive strains. Presence of plasmid could not be correlated with MDR in Salmonella isolates from equids.