Peripheral blood gene expression profile of atherosclerotic coronary artery disease in patients of different ethnicity in Malaysia

The molecular basis of coronary artery disease (CAD) has been widely studied in the western world but there is no published work on the Malaysian population. This study looked at the global gene expression profiling of the peripheral blood of patients with CAD from the 3 main ethnic groups in Malaysia. Male subjects selected were based on angiographically confirmed CAD (≥50% stenosis) and normal control subjects (0% stenosis) with age range of 55.6±5.3 and 51.0±5.5years, respectively. The global gene expression of 12 angiographically documented CAD patients and 11 matched control subjects were performed. The combined group samples identified 6 up regulated differential expression (DE) genes (GHRL, LTA, CBS, HP, ITGA2B, and OLR1) and 12 down regulated DE genes (IL18R1, ITGA2B, IL18RAP, HP, OLR1, SOD2 ITGB3, IL1B, MMP9, PLA2G7, UTS2, and CBS) to be involved in CAD at the fold change of 1.3 with fault discovery rate (FDR) of 1%. Three genes, MMP9, IL1B, and SOD2 were down regulated in all the 3 ethnic groups making them potential biomarker candidates for CAD across all three ethnicities. Further verification in a cohort study is needed.     

Symptomatic change and gastrointestinal quality of life after pancreatectomy

Background

Pancreatectomy affects gastrointestinal (GI) symptoms. Our purpose was to assess the quality of life of pancreatectomy patients in relation to GI function.

Methods

Pancreatectomy patients were asked qualitative, open-ended questions about symptoms. They also completed the Gastrointestinal Symptom Rating Scale (GSRS) for reflux syndrome, acute pain syndrome, indigestion syndrome, diarrhoea syndrome and constipation syndrome.

Results

A total of 52 patients participated. Of these, 69% reported an improvement and 31% reported no change in preoperative symptoms. No patients reported a worsening of symptoms. Half (50%) of the patients experienced new, different symptoms. Median GSRS scores were 0 for reflux syndrome [interquartile range (IQR): 0–1.0], 0 for acute pain syndrome (IQR: 0–1.0), 2.0 for indigestion syndrome (IQR: 1.0–4.0), 2.0 for diarrhoea syndrome (IQR: 0.5–4.5), and 0 for constipation syndrome (IQR: 0–1.0). Whipple operation patients scored higher on the reflux syndrome (0.5 vs. 0; P = 0.08) and indigestion syndrome (3.5 vs. 1.5; P = 0.06) domains. A total of 68% of Whipple operation patients experienced new symptoms, compared with 32% of patients who had undergone other types of pancreatectomy (P = 0.002). Scores of patients who had undergone surgery <2 years and >2 years earlier, respectively, did not differ.

Conclusions

Patients who underwent pancreatectomy frequently experienced an improvement in preoperative symptoms, but also experienced new postoperative symptoms. This was more common after Whipple operations. However, these symptoms were relatively mild in severity. These mild symptoms seem to persist over time.     

Adsorptive,kinetics and regeneration studies of fluoride removal from water using zirconium-based metal organic frameworks

Fluoride contamination has been recognised as one of the major problems worldwide, imposing a serious threat to human health and affecting the safety of drinking water. Adsorption is one of the widely considered appropriate technologies for water defluorination. The present study describes the preparation of a zirconium-based metal organic framework (MOF-801) adsorbent using a solvothermal method and its adsorption efficiency for removal of fluoride ions from water. The morphology of MOF-801 was characterized by PXRD, FESEM and XPS, and the pore structure and surface area were calculated according to BET. It was found that the synthesized MOF-801 showed the distinguishable octahedral shape particle with a lattice spacing of 0.304 nm, indicative of (011) planes of ZrO₂. Adsorption studies were carried out to study the defluorination effectiveness by varying contact time (30–150 min), adsorbent dose (0.3–1.5 g L⁻¹), adsorbate concentration (5–25 mg L⁻¹), as well as kinetics and isotherms. The maximum removal efficiency for fluoride using MOF-801 at equilibrium was found to be 92.3%. Moreover, the adsorption kinetic studies indicate that the overall fluoride adsorption process was best described by pseudo-second-order kinetics. The adsorption data were well-fitted with the Langmuir isotherm model (R² = 0.9925) with maximum adsorption capacity of 19.42 mg g⁻¹. The synthesized MOF-801 had good reusability and was used in up to four cycles for fluoride removal attaining around 79% removal efficiency after the fourth cycle. All the results suggested that the synthesized MOF-801 has potential to be an excellent adsorbent for wastewater defluorination treatment.

A facile solvothermal method is used to prepare octahedral MOF-801 with a lattice spacing of 0.304 nm representative of ZrO₂ (011) planes for water defluorination.     

Regeneration of a deactivated surface functionalised polyacrylonitrile supported Fenton catalyst for use in wastewater treatment

Successful attempts to regenerate a used surface functionalised nanocoated polyacrylonitrile (PAN) catalyst are described here. During use in wastewater treatment, the novel Fenton catalyst (F1) is deactivated due to iron loss caused by acid hydrolysis. In this study the deactivated catalyst (D1) is subjected to reactions with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC), followed by reactions with either hydroxylamine to give sample T1 or hydroxylamine and hydrazine to give sample T2. The samples were then impregnated with iron(iii) salt to give either Fe-T1 or Fe-T2. The catalysts were characterized by Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR), Atomic Absorption (AA) and UV/VIS spectroscopies, Scanning Electron Microscopy (SEM) with energy-dispersive X-ray (EDX) spectroscopy and Electron Spin Resonance (ESR) spectroscopy. The iron on the regenerated catalyst was found to be in complexed form but had deposited iron oxide species as well. The catalysts were tested in batch mode and compared with the fresh modified PAN catalyst in the degradation of the dye Reactive Orange 16 (RO-16) with analysis by UV/VIS spectroscopy. The reactivated catalysts prepared with EDC were found to be more active and faster (as measured at 120 min) in decolourising RO-16 than the fresh catalytic mesh but also with a higher degree of Fe leaching (0.85% loss of iron per gram of Fe-T2 catalyst over 6 cycles compared to 0.32% loss of Fe per gram of F1 catalyst over 6 cycles). This leaching was found not to contribute significantly to degradation of the dye and the preliminary results suggest that the regime can be used for catalyst regeneration encouraging industrial uptake.

Successful attempts to regenerate a used surface functionalised nanocoated polyacrylonitrile (PAN) catalyst are described here.     

Risk of renal cell carcinoma and polymorphism in phase I xenobiotic metabolizing CYP1A1 and CYP2D6 enzymes

The progressive increase in sporadic renal cell carcinoma (RCC) observed in industrialized countries supports the opinion that certain carcinogens present in the environment (tobacco smoke, drugs, pollutants, and dietary constituents) may affect the occurrence and progression of this disease in developing countries like India. The polymorphism of the enzymes involved in metabolism of such environmental factors may, therefore, confer variable propensity to RCC. The possible association between RCC and a polymorphism of the CYP1A1 and CYP2D6 genes specific to the Indian population was examined using peripheral blood DNA from 196 RCC cases and 250 population controls with detailed data of clinicopathologic characteristics for the disease. The CYP1A1 (val) “variant” genotype, which contains at least 1 copy of the CYP1A1 variant alleles, was found to be associated with a 2.03-fold [GG ver. AA/AG, unadjusted OR = 2.03; 95%CI = 1.233–3.342; P = 0.005] increase in the risk of RCC. There was also a significant association (p^trend = 0.034) between higher frequency of RCC subjects containing at least of copy of the CYP1A1 (val) “variant” genotype with III or IV Fuhrman's grade. Whereas, the CYP2D6 polymorphism did not show any association with RCC risk [TT ver. CT/CC, unadjusted OR = 95%CI = 1.233–3.342; P = 0.005]. There was a significant association (p^trend = 0.001) between the poor metabolizer CYP2D6 (TT) and progression towards higher pathological stage of RCC. Our data demonstrate for the first time a significant association between pharmacogenetic polymorphisms of CYP1A1 and risk of RCC development in the Indian population. The findings suggest that inter-individual variation in the phase I metabolic enzymes involved in the fictionalization and detoxification of specific xenobiotics is an important susceptibility factor for development and progression of RCC in Indians.     

Locking Compression Plate in Musculoskeletal Oncology 'a Friend in Need'

Background

We are presenting our experience in the use of locking compression plate (LCP) after juxta-articular oncological resections in addition to its use in pathologic fracture.

Methods

A retrospective audit of skeletal reconstruction using LCP in 25 cases of long bone tumors was performed from 2008 to 2010. Reconstruction following limb salvage surgery was done in 17 patients and internal fixation of pathological fracture was done in 8 patients. All patients were available for > 12 months of follow-up, and thus assessed for union at the resected ends.

Results

There were 8 males and 17 females in the study. The average age at the time of surgery was 30 years (range, 9 to 66 years). The minimum follow-up was 12 months (range, 12 to 32 months). All patients except three went on to heal successfully. Complications occurred in those three patients: wound infection in one, nonunion in another, and periprosthetic fracture in the other patient. In the remaining patients, union was achieved at an average of 6.5 months after reconstruction in curative resection and 4.75 months after fixation of pathological fractures.

Conclusions

Joint sparing limb salvage surgery was made successfully possible after sekeletal reconstruction with LCP. Its use was also quite effective in pathological fractures with poor bone quality. Use of locking plates for musculoskeletal oncological reconstruction resulted in a good and predictable rate of union.     

Cholinergic control of morphine‐induced locomotion in rostromedial tegmental nucleus versus ventral tegmental area sites

M5 muscarinic acetylcholine receptors expressed on ventral tegmental dopamine (DA) neurons are needed for opioid activation of DA outputs. Here, the M5 receptor gene was bilaterally transfected into neurons in the ventral tegmental area (VTA) or the adjacent rostromedial tegmental nucleus (RMTg) in mice by means of a Herpes simplex viral vector (HSV) to increase the effect of endogenous acetylcholine. Three days after HSV‐M5 gene infusion in VTA sites, morphine‐induced locomotion more than doubled at two doses, while saline‐induced locomotion was unaffected. When the HSV‐M5 gene was infused into the adjacent RMTg, morphine‐induced locomotion was strongly inhibited. The sharp boundary between these opposing effects was found where tyrosine hydroxylase (TH) and cholinesterase labelling decreases (?4.00 mm posterior to bregma). The same HSV‐M5 gene transfections in M5 knockout mice induced even stronger inhibitory behavioural effects in RMTg but more variability in VTA sites due to stereotypy. The VTA sites where HSV‐M5 increased morphine‐induced locomotion receive direct inputs from many RMTg GAD‐positive neurons, and from pontine ChAT‐positive neurons, as shown by cholera‐toxin B retrograde tracing. Therefore, morphine‐induced locomotion was decreased by M5 receptor gene expression in RMTg GABA neurons that directly inhibit VTA DA neurons. Conversely, enhancing M5 receptor gene expression on VTA DA neurons increased morphine‐induced locomotion via cholinergic inputs.