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1.
Lett Appl Microbiol ; 75(6): 1579-1589, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36053759

ABSTRACT

The present study evaluated the antibacterial and antibiofilm activity of methanolic extract of Hemidesmus indicus root (MHIR) in combination with amoxicillin and clindamycin against biofilm-forming methicillin-resistant Staphylococcus aureus (MRSA) isolated from milk samples of mastitic cows. Microdilution susceptibility testing and microtitre plate assays were used to evaluate the in vitro efficacy of MHIR and antibiotic combinations against MRSA (n = 12). Furthermore, in vitro findings were validated in a murine model. Minimum inhibitory concentration and minimum biofilm inhibitory concentration of amoxicillin and clindamycin in combination with MHIR were significantly (P < 0·05) lower than when used alone against MRSA. In terms of antibacterial activity, MHIR showed additive interaction (fractional inhibitory concentrationindex >0·5-4) with amoxicillin and clindamycin against all the MRSA isolates, whereas MHIR synergizes (fractional biofilm inhibitory concentrationindex ≤0·5) the antibiofilm activity of amoxicillin and clindamycin against 58·33% and 83·33% of the MRSA isolates respectively. Amoxicillin/clindamycin in combination with MHIR significantly (P < 0·05) reduced disease activity score, and bacterial load and Gram-positive spots in kidney and liver of MRSA-infected mice. The combined efficacy of MHIR and amoxicillin/clindamycin was comparable to clindamycin alone but superior to amoxicillin alone. Hence, the combination of MHIR with amoxicillin/clindamycin is advocated in the treatment of MRSA-associated infections.


Subject(s)
Hemidesmus , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Female , Cattle , Animals , Mice , Clindamycin/pharmacology , Amoxicillin/pharmacology , Methanol , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Biofilms , Staphylococcal Infections/drug therapy , Staphylococcal Infections/veterinary , Staphylococcal Infections/microbiology
2.
Appl Radiat Isot ; 167: 109388, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33011514

ABSTRACT

K2Ca2(SO4)3:Eu nanophosphor was synthesized by chemical coprecipitation method and annealed at different temperatures from 400 to 900 °C. The nanophosphor annealed at 600 °C showed cubic structure with crystallite size ~25 nm. TEM shows morphology of K2Ca2(SO4)3:Eu nanophosphor was in the form of nanorods having diameter ~20 nm and length of ~100-200 nm. These samples were irradiated with gamma radiation for the doses varying from 10 mGy to 10 kGy and their Thermoluminescence (TL) and continuous-wave optically stimulated luminescence (CW-OSL) have been studied. CW-OSL response was found to be maximal for the sample annealed at 600 °C. The TL glow curve of the nanophosphor apparently showed a major peak at around 160 °C accompanied by three low intensity peaks at ~75, 215 and 285 °C. The traps responsible for all the TL peaks in K2Ca2(SO4)3:Eu were also found to be OSL sensitive. The qualitative correlation between TL peaks and CW-OSL response suggested that the traps associated with low temperature peaks are responsible for fast decay and the traps associated with the higher temperature peaks are responsible for slow decay of the OSL signal. OSL response showed linear behavior up to 1 kGy and saturated with further increase in the gamma dose. The wide OSL response makes studied K2Ca2(SO4)3:Eu nanophosphor a good candidate for high dose measurement.

3.
Lett Appl Microbiol ; 71(6): 611-619, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32767781

ABSTRACT

The present study was planned to detect the genes encoding carbapenemases, ESBLs and class 1 integron-integrase among bacteria obtained from retail goat meat. Fermenting and non-fermenting bacterial isolates (n = 57), recovered from 61 goat meat samples, were identified by 16S rRNA gene sequencing. Antimicrobial susceptibility of isolates was tested by the broth dilution method using ceftazidime, cefotaxime, meropenem and imipenem. Plasmids were isolated and tested for their physical characters. Plasmids were subjected to screening of carbapenemase, ESBL and intI1 gene. Conjugation assay was performed using blaNDM -positive isolates as the donor, and Escherichia coli HB101 as the recipient. Isolates showed the high rates of resistance to ceftazidime (77·2%), cefotaxime (70·2%), meropenem (22·8%) and imipenem (17·5%). They showed variability in number and size (~1 to >20 kb) of plasmids. Among all, 1, 4, 13 and 31 isolates showed the blaKPC , blaNDM , blaSHV and blaTEM genes, respectively. The blaKPC-2 gene was observed in one E. coli isolate. The blaNDM-1 gene was detected in Stenotrophomonas maltophilia (n = 2), Acinetobacter baumannii (n = 1) and Ochrobactrum anthropi (n = 1) isolates. These isolates co-harboured the blaTEM and blaSHV genes. The intI1 gene was detected in 22 (38·6%) isolates, and 16 of these isolates showed the carbapenemase and/or ESBL genes. The conjugative movement of blaNDM gene could not be proved after three repetitive mating experiments. The presence of genes encoding carbapenemases and ESBLs in bacteria from goat meat poses public health risks.


Subject(s)
Bacterial Proteins/genetics , Escherichia coli Proteins/genetics , Escherichia coli/isolation & purification , Integrases/genetics , Integrons , Meat/microbiology , beta-Lactamases/genetics , Animals , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/metabolism , Escherichia coli/drug effects , Escherichia coli/enzymology , Escherichia coli/genetics , Escherichia coli Infections/microbiology , Escherichia coli Proteins/metabolism , Food Contamination/analysis , Goats/microbiology , Humans , Integrases/metabolism , Microbial Sensitivity Tests , Plasmids/genetics , Plasmids/metabolism , beta-Lactamases/metabolism
4.
Lett Appl Microbiol ; 71(1): 70-77, 2020 Jul.
Article in English | MEDLINE | ID: mdl-31587338

ABSTRACT

The present study was aimed to detect the carbapenemase, extended-spectrum ß-lactamase (ESBL), and intI1 gene of class 1 integron among fermenting (n = 61) and nonfermenting (n = 10) bacterial isolates recovered from water samples (n = 128). Isolates were identified by 16S rRNA sequencing. These isolates showed reduced-susceptibility to third-generation cephalosporins and carbapenems. The isolates varied in number and size of plasmids (2 kb to >20 kb). Plasmid DNA screening showed 5·6, 7, 11·2 and 26·7% prevalence of blaKPC , blaNDM , blaSHV and blaTEM genes respectively. Diverse blaNDM (blaNDM-1 and blaNDM-4 ) and blaSHV subtypes (blaSHV-2 and blaSHV-11 ) were recorded, unlike the single allelic blaKPC (blaKPC-2 ) and blaTEM (blaTEM-1 ) gene. Of the total 27 bla-gene-producing bacterial isolates, seven isolates co-harboured the carbapenemase genes (blaNDM or blaKPC or the both) along with the ESBL genes (blaSHV or blaTEM ). The intI1 gene of class 1 integron was detected among 12 (44·4%) of ESBL- and/or carbapenemase-harbouring isolates. Gene transferability was seen among four of the 10 Enterobacteriaceae donors. Carbapenemases and ESBLs with class 1 integron among aquatic environmental isolates raise the serious issue of the biosecurity and health of the ecosystem. SIGNIFICANCE AND IMPACT OF THE STUDY: Anthropologically affected and polluted environment harbours the resistance threats, where a diverse bacterial species maintain, develop and exchange genetic determinants that constitute a risk to human and ecological health. The antimicrobial resistance (AMR) in Enterobacteriaceae and non-Enterobacteriaceae bacteria caused the failure of the therapy of last resort (carbapenems) and thus lead to life-threatening infections affecting public health. Surveillance and monitoring of AMR could be important for epidemiological, diagnostic testing and control of pathogens. This is a point-prevalence study reporting the comparative occurrence and co-occurrence of carbapenemase and extended-spectrum ß-lactamase genes among fermenting and nonfermenting bacteria isolated from the aquatic environment in India.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Carbapenems/pharmacology , Drug Resistance, Bacterial/genetics , Enterobacteriaceae/genetics , beta-Lactamases/genetics , Cross-Sectional Studies , Ecosystem , Enterobacteriaceae/drug effects , Enterobacteriaceae/isolation & purification , Humans , India , Integrons , Microbial Sensitivity Tests , Plasmids/genetics , RNA, Ribosomal, 16S , Water
5.
Vet World ; 10(6): 640-649, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28717316

ABSTRACT

Since the embryonic stem cells have knocked the doorsteps, they have proved themselves in the field of science, research, and medicines, but the hovered restrictions confine their application in human welfare. Alternate approaches used to reprogram the cells to the pluripotent state were not up to par, but the innovation of induced pluripotent stem cells (iPSCs) paved a new hope for the researchers. Soon after the discovery, iPSCs technology is undergoing renaissance day by day, i.e., from the use of genetic material to recombinant proteins and now only chemicals are employed to convert somatic cells to iPSCs. Thus, this technique is moving straightforward and productive at an astonishing pace. Here, we provide a brief introduction to iPSCs, the mechanism and methods for their generation, their prevailing and prospective applications and the future opportunities that can be expected from them.

6.
Radiat Environ Biophys ; 55(2): 255-64, 2016 May.
Article in English | MEDLINE | ID: mdl-26846648

ABSTRACT

The thermoluminescence (TL) and optically stimulated luminescence (OSL) properties of human nails and hairs containing α-keratin proteins have been investigated. For the present studies, black hairs and finger nails were selectively collected from individuals with ages between 25 and 35 years. The collected hairs/nails were cut to a size of < 1 mm and cleaned with distilled water to remove dirt and other potential physical sources of contamination. All samples were optically beached with 470 nm of LED light at 60 mW/cm(2) intensity and irradiated by a (60)Co γ source. The hair and nail samples showed overlapping multiple TL glow peaks in the temperature range from 70 to 210 ° C. Continuous wave (CW)-OSL measurements of hair samples at a wavelength of 470 nm showed the presence of two distinct OSL components with photoionization cross section (PIC) values of about 1.65 × 10(-18) cm(2) and about 3.48 × 10(-19) cm(2), while measurements of nail samples showed PIC values of about 6.98 × 10(-18) cm(2) and about 8.7 × 10(-19) cm(2), respectively. This difference in PIC values for hair and nail samples from the same individual is attributed to different arrangement of α-keratin protein concentrations in the samples. The OSL sensitivity was found to vary ± 5 times among nail and hair samples from different individuals, with significant fading (60% in 11 h) at room temperature. The remaining signal (after fading) can be useful for dose estimation when a highly sensitive OSL reader is used. In the absorbed dose range of 100 mGy-100 Gy, both the TL and OSL signals of hair and nail samples showed linear dose dependence. The results obtained in the present study suggest that OSL using hair and nail samples may provide a supplementary method of dose estimation in radiological and nuclear emergencies.


Subject(s)
Hair/metabolism , Keratins/metabolism , Luminescent Measurements , Nails/metabolism , Optical Phenomena , Radiometry/methods , Adult , Female , Hair/radiation effects , Humans , Male , Nails/radiation effects
7.
Annu Int Conf IEEE Eng Med Biol Soc ; 2016: 231-234, 2016 Aug.
Article in English | MEDLINE | ID: mdl-28268319

ABSTRACT

An electroencephalogram (EEG) based image encryption combined with Quantum walks (QW) is encoded in Fresnel domain. The computational version of EEG randomizes the original plaintext whereas QW can serve as an excellent key generator due to its inherent nonlinear chaotic dynamic behavior. First, a spatially coherent monochromatic laser beam passes through an SLM, which introduces an arbitrary EEG phase-only mask. The modified beam is collected by a CCD. Further, the intensity is multiply with the QW digitally. EEG shows high sensitivity to system parameters and capable of encrypting and transmitting the data whereas QW has unpredictability, stability and non-periodicity. Only applying the correct keys, the original image can be retrieved successfully. Simulations and comparisons show the proposed method to be secure enough for image encryption and outperforms prior works. The proposed method opens the door towards introducing EEG and quantum computation into image encryption and promotes the convergence between our approach and image processing.


Subject(s)
Algorithms , Computer Security , Electroencephalography/methods , Image Processing, Computer-Assisted/methods
8.
Nat Commun ; 6: 8201, 2015 Sep 14.
Article in English | MEDLINE | ID: mdl-26365682

ABSTRACT

Exploration of optical properties of organic crystalline semiconductors thin films is challenging due to submicron grain sizes and the presence of numerous structural defects, disorder and grain boundaries. Here we report on the results of combined linear dichroism (LD)/ polarization-resolved photoluminescence (PL) scanning microscopy experiments that simultaneously probe the excitonic radiative recombination and the molecular ordering in solution-processed metal-free phthalocyanine crystalline thin films with macroscopic grain sizes. LD/PL images reveal the relative orientation of the singlet exciton transition dipoles at the grain boundaries and the presence of a localized electronic state that acts like a barrier for exciton diffusion across the grain boundary. We also show how this energy barrier can be entirely eliminated through the optimization of deposition parameters that results in films with large grain sizes and small-angle boundaries. These studies open an avenue for exploring the influence of long-range order on exciton diffusion and carrier transport.

9.
AIDS Care ; 27(12): 1487-92, 2015.
Article in English | MEDLINE | ID: mdl-26186023

ABSTRACT

In India, programme for prevention of mother-to-child transmission (PMTCT) of HIV is primarily implemented through public health system. State AIDS Control Societies (SACSs) encourage private hospitals to set up integrated counselling and testing centres (ICTCs). However, private hospitals of Delhi did not set up ICTCs. Consequently, there is no information on PMTCT interventions in private hospitals of Delhi. This study was undertaken by Delhi SACS during March 2013 through September 2013 to assess status of implementation of PMTCT programme in various private hospitals of Delhi to assist programme managers in framing national policy to facilitate uniform implementation of National PMTCT guidelines. Out of total 575 private hospitals registered with Government of Delhi, 336 (58.4%) catering to pregnant women were identified. About 100 private hospitals with facility of antenatal care, vaginal/caesarean delivery and postnatal care and minimum 10 indoor beds were selected for study. Study sample comprised of large corporate hospitals (≥100 beds; n = 29), medium-sized hospitals (25 to <100 beds; n = 42) and small nursing homes (10 to <25 beds; n = 29). A pre-tested questionnaire was designed to obtain basic information about hospital in context to PMTCT programme. Interviews of heads of obstetrics and gynaecology and paediatric departments were conducted by trained interviewers. It was observed that in private hospitals in year 2012, out of 38,186 antenatal women tested, 52 (0.14%) were detected HIV-positive. However, against National Policy, HIV testing was done without pre/post-test counselling/or consent of women, no PMTCT protocol existed, delivery of HIV-positive women was not undertaken and no efforts were made to link HIV-positive women to antiretroviral treatment. Major intervention observed was medical termination of pregnancy, which indicates lack of awareness in private hospitals about available interventions under national programme. The role of private hospitals in management of HIV in pregnant women must be recognized and mainstreamed in HIV control efforts. There is an urgent need for capacity building of private health care providers to improve standards of practice. National AIDS Control Organization may consider establishing linkages or adopting model developed by some countries with generalized epidemic for delivering PMTCT services in private health sector.


Subject(s)
HIV Infections/prevention & control , Health Plan Implementation/statistics & numerical data , Hospitals, Private , Infectious Disease Transmission, Vertical/prevention & control , Prenatal Care/methods , AIDS Serodiagnosis/statistics & numerical data , Abortion, Induced/statistics & numerical data , Child , Counseling , Delivery, Obstetric/statistics & numerical data , Female , Guideline Adherence , HIV Infections/transmission , Health Policy , Humans , India , Interviews as Topic , Mothers , Pregnancy , Private Sector
10.
Br J Surg ; 102(10): 1278-84, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26095525

ABSTRACT

BACKGROUND: Pelvic exenteration is a potentially curative treatment for locally advanced primary rectal cancer. Previous studies have been limited by small sample sizes and heterogeneous data. A consecutive series of patients was studied to identify the clinicopathological determinants of survival. METHODS: All patients undergoing pelvic exenterative surgery for primary rectal cancer (1992-2014) at this hospital were analysed. The primary outcome measure was 5-year overall survival. Secondary endpoints included length of hospital stay, complication rate, 30-day mortality and disease recurrence rate. Statistical analysis was performed using Kaplan-Meier and Cox regression analysis. RESULTS: A total of 174 patients with a median age of 65 (range 31-90) years were included. Ninety-six patients underwent posterior pelvic exenteration and 78 had total pelvic exenteration. Median follow-up was 48 (range 1-229) months. Two patients (1.1 per cent) died within 30 days of surgery and 16.1 per cent returned to the operating theatre. The 5-year survival rate following complete resection (R0) was 59.3 per cent. In univariable analysis, adverse survival was associated with advanced age (P = 0.003), metastatic disease (P = 0.001), pathological node status (P = 0.001), circumferential resection margin (P = 0.001), local recurrence (P = 0.015) and the need for neoadjuvant therapy (P = 0.039). CONCLUSION: Pelvic exenteration is an aggressive treatment option with a high morbidity rate that provides favourable long-term outcomes in patients with locally advanced primary rectal cancer.


Subject(s)
Pelvic Exenteration/mortality , Rectal Neoplasms/surgery , Risk Assessment/methods , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Hospital Mortality/trends , Humans , Male , Middle Aged , Neoplasm Staging , Rectal Neoplasms/diagnosis , Rectal Neoplasms/mortality , Retrospective Studies , Risk Factors , Survival Rate/trends , Time Factors , United Kingdom/epidemiology
11.
Clin Transl Oncol ; 14(4): 302-11, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22484638

ABSTRACT

INTRODUCTION: Curcumin has been suggested to possess anti-neoplastic properties. As oesophageal adenocarcinoma (OA) and Barrett's oesophagus (BO) represent a neoplastic series, we postulated that curcumin supplementation may slow neoplastic progression at this site. Our aim was to investigate the effects of curcumin in vitro and in vivo on markers of oesophageal cancer progression. METHODS: We investigated the in vitro ability of curcumin to prevent bile acid-induced DNA damage using micronucleus assay and nuclear factor-kappaB (NF-κB) activity in the oesophageal cell lines (OE33) using real-time PCR of the extracted RNA. We also analysed NF-κB p65 activation in curcumin-pre-treated OE33 cells exposed to deoxycholic acid (DCA) using ELISA. In another pilot study, BO patients took a daily 500 mg curcumin tablet for 7 days prior to their endoscopy. In biopsies collected from these patients (n=33, 16 curcumin, 17 control), we examined NF-κB-driven gene expression (interleukin (IL)-8, inhibitor- kappaB (I-κB)) using real-time PCR of the extracted RNA from the biopsy sample. The apoptotic frequency was assessed by counting the number of apoptotic bodies in the epithelial cells from the Barrett's tissue with and without curcumin. RESULTS: In vitro, curcumin (50 µM) significantly abrogated DNA damage and NF-κB activity induced by bile. Pretreating OE33 cells with curcumin (50 µM) completely abolished the ability of DCA (300 µM) to activate NF-κB. In vivo, IL-8 expression was non-significantly suppressed in the curcumin-supplemented patients compared to the squamous control tissue, whilst also showing a doubling in the apoptotic frequency compared to non-supplemented control patients. CONCLUSIONS: Curcumin abrogated bile-driven effects in vitro. The in vivo data also suggests that curcumin supplementation had beneficial effects (increased apoptosis, potentially reduced NF-κB activity) in the Barrett's tissues themselves, despite poor delivery of the curcumin to the oesophagus.


Subject(s)
Adenocarcinoma/pathology , Anticarcinogenic Agents/pharmacology , Antineoplastic Agents/pharmacology , Apoptosis , Barrett Esophagus/pathology , Curcumin/pharmacology , Esophageal Neoplasms/pathology , NF-kappa B/metabolism , Adenocarcinoma/drug therapy , Aged , Barrett Esophagus/drug therapy , Bile/chemistry , Biopsy , Cell Line, Tumor , DNA Damage , Enzyme-Linked Immunosorbent Assay/methods , Esophageal Neoplasms/drug therapy , Female , Humans , Male , Middle Aged , Pilot Projects , Real-Time Polymerase Chain Reaction/methods
12.
Clin. transl. oncol. (Print) ; 14(4): 302-312, abr. 2012.
Article in English | IBECS | ID: ibc-126191

ABSTRACT

INTRODUCTION: Curcumin has been suggested to possess anti-neoplastic properties. As oesophageal adenocarcinoma (OA) and Barrett's oesophagus (BO) represent a neoplastic series, we postulated that curcumin supplementation may slow neoplastic progression at this site. Our aim was to investigate the effects of curcumin in vitro and in vivo on markers of oesophageal cancer progression. METHODS: We investigated the in vitro ability of curcumin to prevent bile acid-induced DNA damage using micronucleus assay and nuclear factor-kappaB (NF-κB) activity in the oesophageal cell lines (OE33) using real-time PCR of the extracted RNA. We also analysed NF-κB p65 activation in curcumin-pre-treated OE33 cells exposed to deoxycholic acid (DCA) using ELISA. In another pilot study, BO patients took a daily 500 mg curcumin tablet for 7 days prior to their endoscopy. In biopsies collected from these patients (n=33, 16 curcumin, 17 control), we examined NF-κB-driven gene expression (interleukin (IL)-8, inhibitor- kappaB (I-κB)) using real-time PCR of the extracted RNA from the biopsy sample. The apoptotic frequency was assessed by counting the number of apoptotic bodies in the epithelial cells from the Barrett's tissue with and without curcumin. RESULTS: In vitro, curcumin (50 μM) significantly abrogated DNA damage and NF-κB activity induced by bile. Pretreating OE33 cells with curcumin (50 μM) completely abolished the ability of DCA (300 μM) to activate NF-κB. In vivo, IL-8 expression was non-significantly suppressed in the curcumin-supplemented patients compared to the squamous control tissue, whilst also showing a doubling in the apoptotic frequency compared to non-supplemented control patients. CONCLUSIONS: Curcumin abrogated bile-driven effects in vitro. The in vivo data also suggests that curcumin supplementation had beneficial effects (increased apoptosis, potentially reduced NF-κB activity) in the Barrett's tissues themselves, despite poor delivery of the curcumin to the oesophagus (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Antineoplastic Agents/pharmacology , Anticarcinogenic Agents/pharmacology , Apoptosis , Barrett Esophagus/pathology , Curcumin/pharmacology , Esophageal Neoplasms/pathology , NF-kappa B/metabolism , Barrett Esophagus/drug therapy , Bile/chemistry , Biopsy/methods , Cell Line, Tumor , DNA Damage , Enzyme-Linked Immunosorbent Assay/instrumentation , Enzyme-Linked Immunosorbent Assay/methods , Esophageal Neoplasms/drug therapy , Pilot Projects , Real-Time Polymerase Chain Reaction/methods
13.
J Hazard Mater ; 192(3): 1040-5, 2011 Sep 15.
Article in English | MEDLINE | ID: mdl-21733625

ABSTRACT

Sorption of technetium by alumina has been studied in absence as well as in presence of humic acid using (95)Tc(m) as a tracer. Measurements were carried out at fixed ionic strength (0.1M NaClO(4)) under varying pH (3-10) as well as redox (aerobic and reducing anaerobic) conditions. Under aerobic conditions, negligible sorption of technetium was observed onto alumina both in absence and in presence of humic acid. However, under reducing conditions (simulated with [Sn(II)] = 10(-6)M), presence of humic acid enhanced the sorption of technetium in the low pH region significantly and decreased at higher pH with respect to that in absence of humic acid. Linear additive as well as surface complexation modeling of Tc(IV) sorption in presence of humic acid indicated the predominant role of sorbed humic acid in deciding technetium sorption onto alumina.


Subject(s)
Aluminum Oxide/analysis , Chemistry/methods , Humic Substances/analysis , Technetium/analysis , Adsorption , Aerobiosis , Aluminum Oxide/chemistry , Anaerobiosis , Colloids/chemistry , Hydrogen-Ion Concentration , Hydrolysis , Models, Theoretical , Potentiometry/methods , Surface Properties
14.
Mutagenesis ; 23(5): 399-405, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18515815

ABSTRACT

Deoxycholic acid (DCA) is a secondary bile acid implicated in various cancers of the gastrointestinal (GI) tract. In oesophageal adenocarcinoma, DCA is believed to contribute to carcinogenesis during reflux where stomach contents enter the lower oesophagus. It is imperative that we understand the mechanisms whereby oesophageal carcinogens function in order that therapeutic options may be developed. We have previously shown that DCA can damage chromosomes and does so through its generation of reactive oxygen species (ROS). We show here, after detailed experiments, that DCA appears to have a non-linear dose response for DNA damage. DCA induces DNA damage (as measured by the micronucleus assay) at doses of 100 microM and higher in oesophageal OE33 cells, but fails to induce such DNA damage below this cut-off dose. We also show that in terms of NF-kappaB activation (as measured by up-regulation of two NF-kappaB target genes) by DCA, a similar dose response is observed. This dose-response data may be important clinically as DCA exposure to the oesophagus may be used as a way to identify the 10% of Barrett's oesophagus patients currently progressing to cancer from the 90% of patients who do not progress. Only quantitative studies measuring DCA concentrations in refluxates correlated with histological progression will answer this question. We further show here that ROS are behind DCAs ability to activate NF-kappaB as antioxidants (epigallocatechin gallate, resveratrol and vitamin C) abrogate DCAs ability to up-regulate NF-kappaB-controlled genes. In conclusion, low doses of DCA appear to be less biologically significant in vitro. If this were to be confirmed in vivo, it might suggest that reflux patients with low DCA concentrations may be at a lower risk of cancer progression compared to patients with high levels of DCA in their refluxate. Either way, antioxidant supplementation may possibly help prevent the deleterious effects of DCA in the whole GI tract.


Subject(s)
DNA Damage , DNA/drug effects , Deoxycholic Acid/toxicity , Esophagus/drug effects , Mutagens/toxicity , NF-kappa B/metabolism , Reactive Oxygen Species/metabolism , Adenocarcinoma/chemically induced , Adenocarcinoma/etiology , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Barrett Esophagus/complications , Cell Line, Tumor , Cell Transformation, Neoplastic/chemically induced , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Esophageal Neoplasms/chemically induced , Esophageal Neoplasms/etiology , Esophageal Neoplasms/genetics , Esophageal Neoplasms/metabolism , Esophagus/metabolism , Esophagus/pathology , Gene Expression/drug effects , Gene Expression Regulation , Humans , Micronucleus Tests
15.
Eur J Vasc Endovasc Surg ; 32(2): 146-8, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16520068

ABSTRACT

Acute pancreatitis is a rare complication after aortic surgery and carries a high mortality. We report the successful management of an infected aortic graft secondary to complicated severe pancreatitis in a 77-year-old man by open drainage of the abscess and replacement of the prosthetic graft with superficial femoro-popliteal vein (SFPV). The patient remains free from infection with a patent graft 8 months later.


Subject(s)
Abscess/microbiology , Blood Vessel Prosthesis/microbiology , Pancreatic Diseases/microbiology , Prosthesis-Related Infections/microbiology , Abscess/therapy , Aged , Anti-Bacterial Agents/therapeutic use , Aortic Aneurysm, Abdominal/surgery , Aortic Rupture/surgery , Drainage , Femoral Vein/transplantation , Humans , Male , Pancreatic Diseases/therapy , Popliteal Vein/transplantation , Prosthesis-Related Infections/therapy
16.
Br J Surg ; 92(11): 1345-53, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16237743

ABSTRACT

BACKGROUND: Parathyroid carcinoma is a rare malignancy affecting 0.5-5 per cent of all patients with primary hyperparathyroidism. This article reviews the literature on the pathogenesis, pathology, clinical features, diagnosis and management of parathyroid carcinoma. METHODS: A Medline search was performed and all relevant English language articles published between 1970 and 2005 were retrieved. The search words included 'parathyroid carcinoma', 'pathology', 'genetics', 'management' and 'radiotherapy'. Secondary references were obtained from key articles. RESULTS AND CONCLUSION: The exact aetiology of parathyroid carcinoma remains obscure. Recently, the HRPT2 gene has been implicated in its pathogenesis and may prove to be a genetic target in future. Surgical resection is the accepted 'gold standard'. There is now a growing consensus on the use of adjuvant radiotherapy as it has been shown to provide a survival benefit.


Subject(s)
Parathyroid Neoplasms , Combined Modality Therapy , Humans , Neoplasm Recurrence, Local/therapy , Parathyroid Neoplasms/diagnosis , Parathyroid Neoplasms/etiology , Parathyroid Neoplasms/therapy , Treatment Outcome
17.
QJM ; 98(1): 29-34, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15625351

ABSTRACT

BACKGROUND: Post-herpetic neuralgia is difficult to treat. Divalproex sodium (valproic acid and sodium valproate in molar ratio 1:1) has been used successfully in the management of various painful neuropathies. AIM: To study the effectiveness and safety of divalproex sodium in the management of post-herpetic neuralgia. DESIGN: Randomized double-blind placebo-controlled trial. METHODS: We enrolled 48 consecutively attending out-patients with post-herpetic neuralgia, out of whom three were excluded (two had insufficient pain, one withdrew consent). Quantification of pain was by Short Form-McGill pain questionnaire (SF-MPQ), visual analogue scale (VAS), present pain intensity score (PPI) and 11 point Likert scale (11 PLS) at the beginning of the study, after 2 weeks, 4 weeks and at the end of the study (8 weeks). We also assessed patients' global impression of change by questionnaire at the end of the study. RESULTS: After 8 weeks treatment with 1000 mg/day divalproex sodium, there was significant reduction in pain: SF-MPQ, 20.47 +/- 2.29 to 11.90 +/- 6.52 (p < 0.0001); PPI 4.0 +/- 0.52 to 1.95 +/- 1.29 (p < 0.0001); VAS 70.17 +/- 9.21 to 31.27 +/- 29.74 (p < 0.0001) and 11 PLS 6.97 +/- 0.73 to 3.63 +/- 2.34 (p < 0.0001) in comparison to placebo (means +/- SEM). The 'global impression of change' questionnaire showed much or moderate improvement in pain in 58.2% of patients receiving divalproex vs. 14.8% of those receiving placebo. The drug was well tolerated by all patients, except one who developed severe vertigo after 10 days of treatment. DISCUSSION: Divalproex sodium provides significant pain relief in patients of post-herpetic neuralgia, with very little incidence of adverse reactions. These data provide a basis for longer trials in a larger group of patients.


Subject(s)
GABA Agents/therapeutic use , Herpes Zoster/complications , Neuralgia/drug therapy , Valproic Acid/therapeutic use , Adult , Aged , Double-Blind Method , Female , GABA Agents/adverse effects , Humans , Male , Middle Aged , Neuralgia/virology , Pain Measurement/methods , Patient Satisfaction , Treatment Outcome , Valproic Acid/adverse effects
18.
Appl Radiat Isot ; 60(5): 621-4, 2004 May.
Article in English | MEDLINE | ID: mdl-15082037

ABSTRACT

The sorption and desorption behaviour of several radionuclides, including 241Am, 152,154Eu, 233U, 137Cs, 90Sr and 90Y was studied under varying acidities using zirconium vanadate as ion exchanger. The sorption follows the order: Cs > Eu > Am >Y > U, while Sr was not taken up by the ion exchanger. A radiochemical separation scheme for the 90Y daughter from its 90Sr parent using zirconium vanadate ion exchanger has been developed. The exchanger was synthesized and characterized in our laboratory.

19.
QJM ; 97(1): 33-8, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14702509

ABSTRACT

BACKGROUND: Various drugs are effective in the management of painful diabetic neuropathy, but none is completely satisfactory. We previously found sodium valproate to be effective and safe in a short-term study. AIM: To test the effectiveness and safety of sodium valproate in the management of painful diabetic neuropathy over 3 months. DESIGN: Randomized double-blind placebo-controlled study. METHODS: Consecutive attending patients with type 2 diabetes mellitus with painful neuropathy were asked to participate in the trial: 48 agreed. Five were excluded: three with HbA(1c) > 11, one with too low a pain level and one who withdrew consent. The remaining 43 were given either drug (group A) or placebo (group B). Each patient was assessed clinically. Quantitative assessment of pain was done by McGill Pain Questionnaire, Visual Analogue Score and Present Pain Intensity, at the beginning of the study, after 1 month and after 3 months. Motor and sensory nerve conduction velocities were measured initially and after 3 months. Liver function tests and other adverse drug-related effects were assessed periodically. RESULTS: Of the 43 patients, four dropped out: one in group A and three in group B. There was significant improvement in pain score in group A, compared to group B, at 3 months (p < 0.001). Changes in electrophysiological data were not significant. The drug was well-tolerated by all patients, except one, who had raised serum AST and ALT levels after 1 month of treatment, and whose treatment was discontinued. DISCUSSION: Sodium valproate is well-tolerated, and provides significant subjective improvement in painful diabetic neuropathy.


Subject(s)
Diabetic Neuropathies/drug therapy , GABA Agents/therapeutic use , Valproic Acid/therapeutic use , Adult , Diabetic Neuropathies/physiopathology , Double-Blind Method , Female , GABA Agents/adverse effects , Humans , Male , Middle Aged , Neural Conduction/drug effects , Pain Measurement/methods , Valproic Acid/adverse effects
20.
QJM ; 96(7): 505-12, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12881593

ABSTRACT

BACKGROUND: According to the WHO, signs of hepatic dysfunction are unusual, and hepatic encephalopathy is never seen in malaria. However, in recent years, isolated cases have been reported from different parts of world. AIM: To identify the evidence for hepatocyte dysfunction and/or encephalopathy in jaundiced patients with falciparum malaria. DESIGN: Prospective observational study. METHODS: We studied 86 adult patients of both sexes who had malaria with jaundice (serum bilirubin > 3 mg%). The main outcome measures were: flapping tremor, deranged psychometric test, level of consciousness, serum bilirubin level, serum aspartate transaminase (AST) and alanine transaminase (ALT) levels, blood ammonia level, viral markers for hepatitis, ultrasonography of liver and gall bladder and electroencephalography (EEG). RESULTS: The range of serum bilirubin was 3-48.2 mg% (mean +/- SD 10.44 +/- 8.71 mg%). The ranges of AST and ALT levels were 40-1120 IU/l (294.47 +/- 250.67 IU/l) and 40-1245 IU/l (371.12 +/- 296.76 IU/l), respectively. Evidence of hepatic encephalopathy was seen in 15 patients. Asterexis was observed in 9 patients, impaired psychometric tests in 12 and altered mental state in 13. Arterial blood ammonia level was 120-427 meq/l (310 +/- 98.39 meq/l). EEG findings included presence of large bilateral synchronous slow waves, pseudo burst suppression and triphasic waves. Four patients died due to multiple organ dysfunction; the others made rapid recoveries. DISCUSSION: There is strong evidence of hepatocyte dysfunction and hepatic encephalopathy in some of these patients, with no obvious non-malarial explanation. Current guidelines may need to be revised.


Subject(s)
Hepatic Encephalopathy/parasitology , Hepatocytes/parasitology , Liver Diseases, Parasitic/complications , Malaria, Falciparum/complications , Adult , Alanine Transaminase/blood , Antimalarials/therapeutic use , Aspartate Aminotransferases/blood , Bilirubin/blood , Biomarkers/blood , Female , Hepatic Encephalopathy/drug therapy , Humans , Jaundice/drug therapy , Jaundice/parasitology , Liver Diseases, Parasitic/diagnosis , Liver Diseases, Parasitic/drug therapy , Malaria, Falciparum/drug therapy , Male , Prospective Studies , Quinine/therapeutic use , Treatment Outcome
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