Anil Kaul

Status of bacterial colonization, Toll-like receptor expression and nuclear factor-kappa B activation in normal and diseased human livers.

Epidemiological data on bacterial translocation (BT), colonization and inflammation in normal human livers is lacking. In this study we investigated the status of bacterial colonization and inflammation in the normal, cirrhotic primary biliary cirrhosis (PBC), and nonalcoholic steatohepatitis (NASH) human liver tissues. Comparatively normal livers showed increased bacterial colonization than PBC and NASH. We analyzed mRNA levels of Toll-like receptors (TLR) 2 and TLR4, and protein levels of TLR4. Phosphorylated IKKα (pIKKα) protein estimation served as a marker for nuclear factor-kappa B (NF-κB) activation. In spite of the increased bacterial colonization in normal liver tissues, lower levels of TLR2/4 mRNA and TLR4 and pIKKα proteins were found compared to PBC and NASH indicating the maintenance of suppressed inflammation and immune tolerance in normal livers. To our knowledge, this is the first clinical evidence showing suppressed inflammation despite bacterial colonization in normal human livers thus maintaining liver immune homeostasis.

Purification and functionalization of nanodiamond to serve as a platform for amoxicillin delivery

Urinary tract infections (UTIs) cost

Estrogen receptor expression in chronic hepatitis C and hepatocellular carcinoma pathogenesis

0.4-0.5 billion a year in the US and is the second most common disease affecting millions of people. As resistance to antibiotics becomes more common, a greater need for alternative treatments is needed. Nanodiamond particles (NDPs) are actively researched as drug delivery platforms due to their biocompatibility, particle size, and stable inert core. This research is aimed at developing NDPs as antibiotic drug delivery platforms for treating UTIs. To this end, 100 nm, 75 nm, 25 nm and 6 nm size NDPs are purified with acid and heat treatment techniques. Raman spectra of the NDPs showed that the acid treatment method resulted in higher diamond yield. Fourier transform infrared spectroscopy (FTIR) studies showed that both purification techniques result in oxygen terminated surface groups. Efficiency of loading amoxicillin on 25 nm NDPs based on electrostatic interaction of NDPs, functionalizing surfaces of NDPs with hydrogen, and polyethylenimine (PEI) are investigated. It is found that the electrostatic and surface hydrogenation approaches are not efficient in loading amoxicillin on the NDPs. On the other hand, PEI functionalized NDPs produced successful loading with amoxicillin as indicated by the presence of the β-lactam peak at 1770 cm(-1), amide peak at 1680 cm(-1), and bond between PEI NH stretching and amoxicillin -COOH group at 3650 cm(-1) by the FTIR spectra. These results are expected to lay the foundation for developing NDP based targeted drug delivery treatment techniques for treating UTIs and other infectious diseases.

Continuous Wireless Monitoring of the Cervical Dilation of a Pregnant Woman

AIM To investigate gender-specific liver estrogen receptor (ER) expression in normal subjects and patients with hepatitis C virus (HCV)-related cirrhosis and hepatocellular carcinoma (HCC). METHODS Liver tissues from normal donors and patients diagnosed with HCV-related cirrhosis and HCV-related HCC were obtained from the NIH Liver Tissue and Cell Distribution System. The expression of ER subtypes, ERα and ERβ, were evaluated by Western blotting and real-time RT-PCR. The subcellular distribution of ERα and ERβ was further determined in nuclear and cytoplasmic tissue lysates along with the expression of inflammatory [activated NF-κB and IκB-kinase (IKK)] and oncogenic (cyclin D1) markers by Western blotting and immunohistochemistry. The expression of ERα and ERβ was correlated with the expression of activated NF-κB, activated IKK and cyclin D1 by Spearman’s correlation. RESULTS Both ER subtypes were expressed in normal livers but male livers showed significantly higher expression of ERα than females (P < 0.05). We observed significantly higher mRNA expression of ERα in HCV-related HCC liver tissues as compared to normals (P < 0.05) and ERβ in livers of HCV-related cirrhosis and HCV-related HCC subjects (P < 0.05). At the protein level, there was a significantly higher expression of nuclear ERα in livers of HCV-related HCC patients and nuclear ERβ in HCV-related cirrhosis patients as compared to normals (P < 0.05). Furthermore, we observed a significantly higher expression of phosphorylated NF-κB and cyclin D1 in diseased livers (P < 0.05). There was a positive correlation between the expression of nuclear ER subtypes and nuclear cyclin D1 and a negative correlation between cytoplasmic ER subtypes and cytoplasmic phosphorylated IKK in HCV-related HCC livers. These findings suggest that dysregulated expression of ER subtypes following chronic HCV-infection may contribute to the progression of HCV-related cirrhosis to HCV-related HCC. CONCLUSION Gender differences were observed in ERα expression in normal livers. Alterations in ER subtype expression observed in diseased livers may influence gender-related disparity in HCV-related pathogenesis.

Designing a wireless sensor system for continuous monitoring of the cervical dilation of a pregnant woman

A novel electronic sensor system is designed to continuously monitor the dilation of the cervix of a pregnant female approaching labor and delivery. The system is capable of wirelessly transmitting the progress of dilation to a central monitoring agency that can get in touch with the attending physician and/or the hospital of the pregnant female. Using wireless telephony, the monitoring agency and/or the physician can advise the female about the medical care she needs at that moment, even though the female might be at her home, or away from home and away from the medical facility.

Nanodiamonds facilitate killing of intracellular uropathogenic e. Coli in an in vitro model of urinary tract infection pathogenesis

A novel electronic sensor system is designed to continuously monitor the dilation of the cervix of a pregnant female approaching labour and delivery. The system is capable of wirelessly transmitting the progress of dilation to a central monitoring agency that can get in touch with the attending physician and/or the hospital of the pregnant female. Using wireless telephony, the monitoring agency and/or the physician can advise the female about the medical care she needs at that moment, even though the female might be at her home or away from home, and away from the medical facility. This is an expanded version of a paper presented at the 3rd IEEE International Workshop on Medical Measurements and Applications, 9 10 May 2008, Ottawa, ON, Canada.

PROTEIN KINASE C – ZETA INHIBITORS: A NEW HOPE FOR CONTROLLING MATERNAL INTRAUTERINE INFECTION INDUCED PREMATURE BIRTH.

About 25–44% of women will experience at least one episode of recurrent UTI and the causative agent in over 70% of UTI cases is uropathogenic Escherichia coli (UPEC). UPEC cause recurrent UTI by evading the bladder’s innate immune system through internalization into the bladder epithelium where antibiotics cannot reach or be effective. Thus, it is important to develop novel therapeutics to eliminate these intracellular pathogens. Nanodiamonds (NDs) are biocompatible nanomaterials that serve as promising candidates for targeted therapeutic applications. The objective of the current study was to investigate if 6 or 25 nm NDs can kill extracellular and intracellular UPEC in infected bladder cells. We utilized the human bladder epithelial cell line, T24, and an invasive strain of UPEC that causes recurrent UTI. We found that acid-purified 6 nm NDs displayed greater antibacterial properties towards UPEC than 25 nm NDs (11.5% vs 94.2% CFU/mL at 100 μg/mL of 6 and 25 nm, respectively; P<0.001). Furthermore, 6 nm NDs were better than 25 nm NDs in reducing the number of UPEC internalized in T24 bladder cells (46.1% vs 81.1% CFU/mL at 100 μg/mL of 6 and 25 nm, respectively; P<0.01). Our studies demonstrate that 6 nm NDs interacted with T24 bladder cells in a dose-dependent manner and were internalized in 2 hours through an actin-dependent mechanism. Finally, internalization of NDs was required for reducing the number of intracellular UPEC in T24 bladder cells. These findings suggest that 6 nm NDs are promising candidates to treat recurrent UTIs.

A comparative review of HLA associations with hepatitis B and C viral infections across global populations.

Arun Kumar 1 , Showket Hussain 2 , Ankita Singh 3 , Rashmi Kaul 4 , Anil Kaul 5 , Rahul Prabhas 6 , Sunil Kumar Srivastava 7 , Nitin Goel 8 and V. K. Narang 9 . 1. M.Sc. Biotechnology, Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT)Bombay, Mumbai, India 2. Scientist C, Division of Molecular Oncology, National Institute of Cancer Prevention and Research (NICPR), ICMR, Noida, India. 3. ICMR-Post Doctoral Fellow, National Institute of Cancer Prevention and Research (NICPR), ICMR, Noida, India. 4. Associate Professor, Department of Biochemistry and Microbiology, Oklahoma State University Center for Health Sciences, USA. 5. Director of clinical laboratories and Associate professor of obstetrics and gynecology, Oklahoma State University Center for Health Sciences, USA. 6. M.Sc. Medical Microbiology, M.M. Institute of Medical Science and Research, Ambala, Haryana, India. 7. Associate Professor, Department of Microbiology, Swami Shraddhanand College, University of Delhi, Delhi India. 8. Assistant Professor, Department of Microbiology, M.M. Institute of Medical Science and Research, Ambala, Haryana, India. 9. Professor and Head of the Department, Department of Microbiology, Glocal Medical College, Saharanpur, UP, India. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History