The Viral Knock: Ameliorating Cancer Treatment with Oncolytic Newcastle Disease Virus.

The prospect of cancer treatment has drastically transformed over the last four decades. The side effects caused by the traditional methods of cancer treatment like surgery, chemotherapy, and radiotherapy through the years highlight the prospect for a novel, complementary, and alternative cancer therapy. Oncolytic virotherapy is an evolving treatment modality that utilizes oncolytic viruses (OVs) to selectively attack cancer cells by direct lysis and can also elicit a strong anti-cancer immune response. Newcastle disease virus (NDV) provides a very high safety profile compared to other oncolytic viruses. Extensive research worldwide concentrates on experimenting with and better understanding the underlying mechanisms by which oncolytic NDV can be effectively applied to intercept cancer. This review encapsulates the potential of NDV to be explored as an oncolytic agent and discusses current preclinical and clinical research scenarios involving various NDV strains.

Activity of siderophores against drug-resistant Gram-positive and Gram-negative bacteria.

Infections by drug-resistant bacteria are life-threatening. As iron is a vital element for the growth of bacteria, iron-chelating agents (siderophores) can be used to arrest their multiplication. Exogenous siderophores - exochelin-MS and deferoxamine-B - were evaluated for their inhibitory activity against methicillin-resistant Staphylococcus aureus and metallo-ß-lactamase producers - Pseudomonas aeruginosa and Acinetobacter baumannii - by disc diffusion, micro-broth dilution, and turbidimetric growth assays. The drug-resistant isolates were inhibited by the synergistic activity of siderophores and antibiotics. Minimum inhibitory concentration of exochelin-MS+ampicillin for different isolates was between 0.05 and 0.5 mg/mL. Minimum inhibitory concentration of deferoxamine-B+ampicillin was 1.0 mg/mL and greater. Iron-chelation therapy could provide a complementary approach to overcome drug resistance in pathogenic bacteria.

Preliminary evaluation of anti-tuberculosis potential of siderophores against drug-resistant Mycobacterium tuberculosis by mycobacteria growth indicator tube-drug sensitivity test.

BACKGROUND: Alternative treatment strategies have become essential in overcoming the problem of drug-resistant Mycobacterium tuberculosis (Mtb). In this preliminary in vitro study, the anti-tuberculosis (anti-TB) activity of exogenous iron chelators (xenosiderophores) such as Exochelin-MS (Exo-MS) and Deferoxamine-B (DFO-B) was evaluated against ten multi-drug-resistant (MDR) and seven pyrazinamide-resistant (PZA R ) Mtb isolates. METHODS: Mycobacteria Growth Indicator Tube-Drug Susceptibility Test was used to assess the anti-TB effect of Exo-MS or DFO-B individually and their combinations with isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA). RESULTS: For the MDR-Mtb isolates, Exo-MS alone inhibited two out of the five isolates tested. Whereas, DFO-B alone inhibited nine out of the ten MDR isolates tested. For PZA-resistant Mtb isolates, both Exo-MS and DFO-B individually inhibited five out of the seven isolates. The MIC of Exo-MS in combination with INH, RIF and PZA remained the same. The MIC of DFO-B decreased when tested in combination with INH, RIF and PZA. CONCLUSIONS: Exo-MS and DFO-B were shown to have activity against drug-resistant Mtb isolates. Therefore, these xenosiderophores may be useful adjuncts to antibiotics in overcoming the problem of drug-resistant Mtb in clinical setting.

Effect of microbial siderophores on mammalian non-malignant and malignant cell lines.

BACKGROUND: Iron is a vital nutrient for all cells, and malignant cells have a higher requirement for the metal due to their rapid multiplication. Bacterial siderophores can be used to reduce free ferric ion concentration from the cellular environment. METHODS: In the present study, we have evaluated effect of three siderophores - exochelin-MS, mycobactin S and deferoxamine B on the proliferation of mammalian cell lines using MTT assay. RESULTS: These siderophores caused a significant decrease in the viability of malignant cells, without significantly affecting non-malignant cells. CONCLUSIONS: Based on these results, we suggest that iron-chelation therapy could be explored as an adjunctive therapeutic option against cancer along with other therapies.

Polymerase chain reaction for the rapid diagnosis of tuberculous meningitis.

Polymerase chain reaction (PCR) based on the amplification of a 169 bp DNA fragment specific for the Mycobacterium tuberculosis complex was evaluated for the rapid diagnosis of tuberculous meningitis (TBM). A total of 105 CSF specimens from clinically suspected cases of TBM were studied. Clinical details of the cases and cytochemical parameters of the CSF specimens were recorded. For PCR 10 CSF specimens from cases other than TBM, 4 non-mycobacterial culture isolates (one strain of E coli, one strain of proteus species and 2 strains of salmonella species) and one sample of sterile distilled water were processed as negative controls. For positive control standard culture of Mycobacterium tuberculosis H37Rv was processed with every batch of specimens. Besides PCR, smear for AFB by the Ziehl-Neelsen (ZN) and the fluorochrome method and culture on Lowenstein-Jensen medium was also carried out. By PCR, 31.42% specimens were found positive, whereas by conventional culture on Lowenstein-Jensen medium only 3.8% specimens were positive.

Molecular epidemiology and clinical implications of TT virus (TTV) infection in Indian subjects.

GOALS: This study was aimed at obtaining data on the epidemiology and clinical course of TT virus (TTV) infections among Indian subjects. BACKGROUND: The TTV is a nonenveloped DNA virus, first identified in the peripheral blood of individuals with posttransfusion hepatitis of unknown etiology. There has been much conjecture regarding the disease association of this virus. STUDY: A total of 494 serum specimens from various groups of high-risk and control subjects were screened for TTV DNA by a semi-nested PCR, using the ORF1-derived N22 primers. The sera were also screened for the HBsAg surface antigen by an ELISA, HCV RNA by a 5' NCR-based RT-PCR and GBV-C/HGV RNA by a 5' UTR-based RT-PCR. The clinical and hepatic profiles of the various subjects were also studied. Seventy-one randomly picked TTV isolates were directly sequenced and their phylogeny was studied. RESULTS: TTV showed an overall positivity rate of 45.34% with a significant higher prevalence of 52.9% among the high-risk subjects as against a prevalence of 28% among healthy control subjects (P < 0.001). Abnormal liver function profiles were frequent among TTV viremic individuals and among the acute hepatitis cases studied a higher mortality rate correlated with a superimposed TTV infection. The 71 TTV isolates sequenced were found to belong to genotype 1a being closely homologous to TTV prototype TA278. CONCLUSION: The TT virus shows a significant prevalence in the Indian population, particularly among subjects at risk for acquiring parenterally transmitted infections. Our study corroborates a putative role of the virus in the etiology of liver disease, particularly in coinfection with other agents.

GB virus C/hepatitis G virus infection in Indian blood donors and high-risk groups.

The hepatitis G virus (HGV) or GB virus C (GBV-C) was discovered in 1995 as a putative agent of post-transfusion, non-A-E hepatitis. The present study was carried out with the aim to find the prevalence of this virus among various subject groups at risk for parenteral transmission as well as in healthy control subjects both individually and along with other parenterally transmitted hepatitis viruses. Of the 402 subjects tested, 6.22% were positive for the HBsAg surface antigen, 7.21% were positive for HCV RNA while only 2.24% were seen to be carriers of the HGV/GBV-C RNA. All the HGV/GBV-C positive cases were either multi-transfused thalassaemic subjects or hemodialysis patients. None of the healthy control subjects showed presence of the virus. Seven of the HGV/GBV-C positive subjects showed co-infection with one or more additional virological markers. Also, of the 9 HGV/GBV-C positive subjects, 5 showed elevated ALT levels while 4 showed elevated alkaline phosphatase levels. Overall our findings seem to indicate that HGV infections generally are asymptomatic, transient and self-limiting and the virus does not seem to show a very high prevalence among the Indian population.

Study of fungal and bacterial infections of the diabetic foot.

Microbiological study for aerobic organisms, anaerobic organisms and fungi from 105 cases of diabetic foot ulcers was carried out to determine the aetiological agents and their antibiograms. Out of 265 microbial isolates obtained, 160 were aerobes, 50 anaerobes and 55 fungal strains. Polymicrobial infection was observed in 73 (69.5%) cases. The most frequently isolated aerobic microorganisms were Staphylococcus aureus and Pseudomonas aeruginosa. Among the anaerobes Bacteroides melaninogenicus and Bacteroides fragilis were most common. Candida species were preponderant among the fungal isolates. Antimicrobial sensitivity pattern of the isolates is discussed in detail.