Mortality in hepatitis C patients who achieve a sustained viral response compared to the general population

Background & Aims: The number of people living with previous hepatitis C infection that have attained a sustained viral response (SVR) is expected to grow rapidly. So far, the prognosis of this group relative to the general population is unclear. Methods: Individuals attaining SVR in Scotland in 1996–2011 were identified using a national database. Through record-linkage, we obtained cause-specific mortality data complete to Dec 2013. We calculated standardised mortality ratios (SMRs) to compare the frequency of mortality in SVR patients to the general population. In a parallel analysis, we used Cox regression to identify modifiable patient characteristics associated with post-SVR mortality. Results: We identified 1824 patients, followed on average for 5.2 years after SVR. In total, 78 deaths were observed. Overall, all-cause mortality was 1.9 times more frequent for SVR patients than the general population (SMR: 1.86; 95% confidence interval (CI): 1.49–2.32). Significant cause-specific elevations were seen for death due to primary liver cancer (SMR: 23.50; 95% CI: 12.23–45.16), and death due to drug-related causes (SMR: 6.58, 95% CI: 4.15–10.45). Together these two causes accounted for 66% of the total excess death observed. All of the modifiable characteristics associated with increased mortality were markers either of heavy alcohol use or injecting drug use. Individuals without these behavioural markers (32.8% of cohort) experienced equivalent survival to the general population (SMR: 0.70; 95% CI: 0.41–1.18) Conclusions: Mortality in Scottish SVR patients is higher overall than the general population. The excess was driven by death from drug-related causes and liver cancer. Health risk behaviours emerged as important modifiable determinants of mortality in this population. Lay summary: Patients cured of hepatitis C through treatment had a higher mortality rate overall than the general population. Most of the surplus mortality was due to drug-related causes and death from liver cancer. A history of heavy alcohol and injecting drug use were associated with a higher mortality risk

Interaction of RuIII(EDTA) with cellular thiols and O2: biological implications thereof

Reaction of [RuIII(EDTA)(CyS)]2− (edta4− = ethylenediaminetetraacetate; CySH = cysteine) with molecular oxygen (O2) has been studied as a function of pH (4.0–8.0) and cysteine concentration (0.2–2.0 mM) at room temperature (25 °C). Biological activities of the [Ru(EDTA)]/CySH/O2 system pertaining to cleavage of supercoiled plasmid DNA to its nicked open circular form has been explored in this work. Results are discussed in regard to the reaction of the ruthenium(III)-complex with molecular oxygen) and a working mechanism is proposed for the biological activities of the ruthenium(III)-complex in the presence of O2

Interaction of Ru^III(EDTA) with cellular thiols and O₂: biological implications thereof

<div><p>Reaction of [Ru^III(EDTA)(CyS)]²⁻ (edta⁴⁻ = ethylenediaminetetraacetate; CySH = cysteine) with molecular oxygen (O₂) has been studied as a function of pH (4.0–8.0) and cysteine concentration (0.2–2.0 mM) at room temperature (25 °C). Biological activities of the [Ru(EDTA)]/CySH/O₂ system pertaining to cleavage of supercoiled plasmid DNA to its nicked open circular form has been explored in this work. Results are discussed in regard to the reaction of the ruthenium(III)-complex with molecular oxygen) and a working mechanism is proposed for the biological activities of the ruthenium(III)-complex in the presence of O₂.</p></div

Iron(III) Coordinated Polymeric Nanomaterial: A Next-Generation Theranostic Agent for High-Resolution T₁‑Weighted Magnetic Resonance Imaging and Anticancer Drug Delivery

Theranostic-based nanomedicine plays a crucial role in the field of cancer therapy. This is due to having the capability to combine both therapy and diagnosis together in a single system. Herein a new class of metal–ligand-based nanocarrier in a norbornene backbone has been designed as a theranostic system. Fe³⁺-terpyridine complex <b>(Fe-Tpy)</b> has been used here as T₁ contrast agent for high-resolution MR imaging, and hydrazone-linked doxorubicin is used for effective pH-responsive delivery. Polyethylene glycol functionalized with a folic acid (peg folate) motif is used to make the entire polymeric system dispersible in water for longer retention and site-specific therapy. All these specialty functional groups are anchored in a single system by using the ring-opening metathesis polymerization (ROMP) technique under the norbornene backbone. Relaxivity study and 1D image experiments have shown the utility of <b>Fe-Tpy</b> complex as an effective T₁ contrast agent. <i>In vitro</i> studies are performed to confirm the promising potentiality of the nanocarrier as the efficient nanotheranostic system in prostate cancer

Super paramagnetic Norbornene Copolymer Functionalized with Biotin and Doxorubicin: A Potential Unique Site-Specific Theranostic Agent

Polymer-based nanosystems have been extensively explored either as therapeutic agents or bioimaging probes in the cancer diagnosis. However, very few systems are successful in combining both therapy and imaging. Herein, a new class of norbornene based copolymer, <b>Nor-Dox-Cob-Btn</b> is proposed as potential theranostics agent for tumor diagonosis. The copolymer (<b>Nor-Dox-Cob-Btn</b>) with doxorubicin, cobalt carbonyl complex, and biotin as pendent functionalized group is synthesized, using ring opening metathesis polymerization (ROMP). The cell viability, drug release, NMR relaxation, NMR 1-D image and Epi fluorescence microscopy studies on <b>Nor-Dox-Cob-Btn</b> nanocarrier are thoroughly studied. The effect of nanocarrier on transverse relaxation (<i>T</i>₂) of water molecule and NMR 1-D image suggest that the nanocarrier has the potential application in magnetic resonance imaging agent. The <i>T</i>₂-weighted MRI agent, along with biotin receptor assisted pH responsive doxorubicin release from <b>Nor-Dox-Cob-Btn</b>, prompts us to envision this newly developed polymer for future application in theranostics