Incidence of thrombosis in perioperative and non-operative myocardial infarction.

BACKGROUND: The contribution of thrombosis to the aetiology of perioperative myocardial infarction (MI) is uncertain. We used optical coherence tomography (OCT) to determine the presence of thrombus and plaque morphology in patients experiencing a perioperative MI and matched patients experiencing a non-operative MI using OCT. METHODS: We conducted a single-centre, prospective, cohort study. Thirty patients experiencing a perioperative MI and 30 matched patients experiencing a non-operative MI, without ST elevation, underwent OCT to determine the presence of thrombus and culprit lesion plaque morphology. Angiography and OCT were performed a mean of 1.93(1.09) days and 1.53(0.68) days after the onset of perioperative and non-operative MI, respectively. OCT images were evaluated by an independent core laboratory without knowledge of whether the patient had suffered a perioperative or non-operative MI. RESULTS: We identified thrombus at the culprit lesion in four of 30 patients (13.3%) who experienced a perioperative MI and in 20 of 30 patients (66.7%) who experienced a non-operative MI, P<0.01. The only non-culprit lesion with thrombus was in a perioperative MI patient who also had a culprit lesion thrombus. Perioperative and non-operative MI culprit lesions demonstrated fibroatheroma in 18 patients (60.0%) us 20 patients (66.7%), respectively (P=0.52) and thin cap fibroatheroma in one patient (3.3%) us five patients (16.7%), respectively (P=0.11). One perioperative MI patient (3.3%) suffered a cardiac death and no non-operative MI patient died during the 30-day follow-up. CONCLUSIONS: Thrombosis was less common in perioperative than non-operative MI, despite similar underlying plaque morphology.

A correlation study between mean platelet volume and platelet aggregation study in acute coronary syndrome patients.

INTRODUCTION: Platelets play an important role in cardiovascular disease mainly in the development of acute thrombotic events. Elevated platelet indices have been proposed as a risk factor for acute coronary syndrome (ACS). It remains uncertain whether increased platelet indices are the result or the cause of ACS. AIM AND OBJECTIVE: This study aimed to correlate mean platelet volume (MPV) and platelet aggregation response to know the functional status of platelets based on their size. MATERIALS AND METHODS: A total of 50 patients with ST-segment elevation ACS (STE-ACS) or non-ST-segment elevation ACS (NSTE-ACS) were included and their MPV was measured and platelet aggregometry was performed. Patients were divided into two groups, patients with MPV ≤9.1 fl as group 1 and those with MPV >9.1 fl as group 2. The mean maximum platelet aggregation response (MMPAR) with ADP, Collagen, and Epinephrine, of both the groups, were compared. MMPAR to ADP, Collagen, and Epinephrine in group 1 was 74.47%, 66.13%, and 72.9%, respectively, and in group 2, 72.94%, 59.97%, and 72.43%, respectively. There was no statistically significant difference in the MMPAR to ADP, Collagen, and Epinephrine among the two groups. CONCLUSION: Increased MPV does not indicate the platelets are hyperreactive. An increase in MPV may be because of the increased release of immature platelets from bone marrow as there is increased consumption of platelets at the site of thrombus formation in ACS.

Advanced 3D In Vitro Lung Fibrosis Models: Contemporary Status, Clinical Uptake, and Prospective Outlooks.

Fibrosis has been characterized as a global health problem and ranks as one of the primary causes of organ dysfunction. Currently, there is no cure for pulmonary fibrosis, and limited therapeutic options are available due to an inadequate understanding of the disease pathogenesis. The absence of advanced in vitro models replicating dynamic temporal changes observed in the tissue with the progression of the disease is a significant impediment in the development of novel antifibrotic treatments, which has motivated research on tissue-mimetic three-dimensional (3D) models. In this review, we summarize emerging trends in preparing advanced lung models to recapitulate biochemical and biomechanical processes associated with lung fibrogenesis. We begin by describing the importance of in vivo studies and highlighting the often poor correlation between preclinical research and clinical outcomes and the limitations of conventional cell culture in accurately simulating the 3D tissue microenvironment. Rapid advancement in biomaterials, biofabrication, biomicrofluidics, and related bioengineering techniques are enabling the preparation of in vitro models to reproduce the epithelium structure and operate as reliable drug screening strategies for precise prediction. Improving and understanding these model systems is necessary to find the cross-talks between growing cells and the stage at which myofibroblasts differentiate. These advanced models allow us to utilize the knowledge and identify, characterize, and hand pick medicines beneficial to the human community. The challenges of the current approaches, along with the opportunities for further research with potential for translation in this field, are presented toward developing novel treatments for pulmonary fibrosis.

The relationship between anti-idursulfase antibody status and safety and efficacy outcomes in attenuated mucopolysaccharidosis II patients aged 5 years and older treated with intravenous idursulfase.

In the pivotal phase II/III trial of idursulfase administered intravenously to treat mucopolysaccharidosis II, approximately half of the patients developed antibodies to idursulfase. This post-hoc analysis of data from the phase II/III trial and extension study examined the relationship between antibody status and outcomes. A total of 63 treatment-naïve patients received 0.5 mg/kg of intravenous idursulfase weekly for two years. Thirty-two patients (51%) were positive for anti-idursulfase IgG antibodies, 23 of whom (37%) became persistently positive. All patients who developed an antibody response did so by their scheduled Week 27 study visit. Positive antibody status appeared to have no statistically significant effect upon changes in six-minute walk test distance, percent predicted forced vital capacity, or liver and spleen volume. All patients showed significant decreases in urinary GAG levels, although the antibody positive group maintained somewhat higher urinary GAG levels than their antibody-negative counterparts at the end of study (138.7 vs. 94.7 µg/mg creatinine, p = 0.001). Antibody positivity was not associated with a higher event rate for serious adverse events. Among patients who had no prior infusion-related reactions, antibody positive patients were 2.3 times more likely to have a first infusion-related reaction than those who would remain negative (p = 0.017); the risk increased to 2.5 times more likely for those who were persistently positive (p = 0.009). These differences in risk disappeared among patients with a previous infusion-related reaction, likely because of preventive measures. A genotype analysis for the 36 patients with available data found that patients with nonsense or frameshift mutations may be more likely to develop antibodies, to experience infusion-related reactions, and to have a reduced uGAG response than those with missense mutations, suggesting the possibility that antibodies are not a driver of clinical outcomes but rather a marker for genotype.

Novel study on enhancing the ignition pattern of waste and inedible feedstock in a modified diesel engine-enhancing its effectiveness as renewable alternative.

The objective of the present investigation is to enhance the performance of diesel engine using Capparis spinoza fatty acid distillate biodiesel (CFAB100) at various compression ratios. The experiments were carried out at compression ratios of 16.5:1, 17.5:1, 18.5:1, and 19.5:1. It was noted that an increase in compression ratio from 16.5 to 18.5 resulted in better engine characteristics for CFAB100 and reduced at compression ratio 19.5. Brake-specific fuel consumption of CFAB100 decreased from 0.42 to 0.33 kg/kWh with an increase in compression ratio. The brake thermal efficiency of CFAB100 at a compression ratio of 16.5 is 29.64% lower than diesel, whereas it is 11.32% low at a compression ratio of 18.5. The brake thermal efficiency of CFAB100 is 26.03% higher at a compression ratio of 18.5 compared to 16.5. Due to shorter ignition delay and reduced premixed combustion, the net heat release rate of CFAB100 is lower than diesel at all compression ratios. The peak cylinder pressure for diesel is 56.21 bar, and CFAB100 at compression ratios 16.5, 17.5, 18.5, and 19.5 were 52.36, 55.12, 61.02 and 58.25 bar at full load condition. CFAB100, at a compression ratio of 18.5, had the highest nitrogen oxide emissions (2400 ppm). Carbon monoxide, unburnt hydrocarbon, and smoke showed an average reduction of 46.58%, 40.68%, and 54.89%, respectively, when the compression ratio varied between 16.5 and 19.5. At an optimum compression ratio of 18.5, the CFAB100 resulted in improved performance and emission characteristics that can replace diesel to a possible extent.

Factors associated with mortality among moderate and severe patients with COVID-19 in India: a secondary analysis of a randomised controlled trial.

OBJECTIVE: Large data on the clinical characteristics and outcome of COVID-19 in the Indian population are scarce. We analysed the factors associated with mortality in a cohort of moderately and severely ill patients with COVID-19 enrolled in a randomised trial on convalescent plasma. DESIGN: Secondary analysis of data from a Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease. SETTING: 39 public and private hospitals across India during the study period from 22 April to 14 July 2020. PARTICIPANTS: Of the 464 patients recruited, two were lost to follow-up, nine withdrew consent and two patients did not receive the intervention after randomisation. The cohort of 451 participants with known outcome at 28 days was analysed. PRIMARY OUTCOME MEASURE: Factors associated with all-cause mortality at 28 days after enrolment. RESULTS: The mean (SD) age was 51±12.4 years; 76.7% were males. Admission Sequential Organ Failure Assessment score was 2.4±1.1. Non-invasive ventilation, invasive ventilation and vasopressor therapy were required in 98.9%, 8.4% and 4.0%, respectively. The 28-day mortality was 14.4%. Median time from symptom onset to hospital admission was similar in survivors (4 days; IQR 3-7) and non-survivors (4 days; IQR 3-6). Patients with two or more comorbidities had 2.25 (95% CI 1.18 to 4.29, p=0.014) times risk of death. When compared with survivors, admission interleukin-6 levels were higher (p<0.001) in non-survivors and increased further on day 3. On multivariable Fine and Gray model, severity of illness (subdistribution HR 1.22, 95% CI 1.11 to 1.35, p<0.001), PaO2/FiO2 ratio <100 (3.47, 1.64-7.37, p=0.001), neutrophil lymphocyte ratio >10 (9.97, 3.65-27.13, p<0.001), D-dimer >1.0 mg/L (2.50, 1.14-5.48, p=0.022), ferritin ≥500 ng/mL (2.67, 1.44-4.96, p=0.002) and lactate dehydrogenase ≥450 IU/L (2.96, 1.60-5.45, p=0.001) were significantly associated with death. CONCLUSION: In this cohort of moderately and severely ill patients with COVID-19, severity of illness, underlying comorbidities and elevated levels of inflammatory markers were significantly associated with death. TRIAL REGISTRATION NUMBER: CTRI/2020/04/024775.

Identifying women with severe angiographic coronary disease.

OBJECTIVES: To determine sex/gender differences in the distribution of risk factors according to age and identify factors associated with the presence of severe coronary artery disease (CAD). DESIGN: We analysed 23,771 consecutive patients referred for coronary angiography from 2000 to 2006. SUBJECTS: Patients did not have previously diagnosed CAD and were referred for first diagnostic angiography. OUTCOME MEASURES: Patients were classified according to angiographic disease severity. Severe CAD was defined as left main stenosis > or = 50%, three-vessel disease with > or = 70% stenosis or two-vessel disease including proximal left anterior descending stenosis of > or = 70%. Univariate and multivariate logistic regression was used to assess the association between risk factors and angina symptoms with severe CAD. RESULTS: Women were less likely to have severe CAD (22.3% vs. 36.5%) compared with men. Women were also significantly older (69.8 +/- 10.6 vs. 66.3 +/- 10.7 years), had higher rates of diabetes (35.0% vs. 26.6%), hypertension (74.8% vs. 63.3%) and Canadian Cardiovascular Society (CCS) class IV angina symptoms (56.7% vs. 47.8%). Men were more likely to be smokers (56.9% vs. 37.9%). Factors independently associated with severe CAD included age (OR = 1.05; 95% CI 1.05-1.05, P < 0.01), male sex (OR = 2.43; CI 2.26-2.62, P < 0.01), diabetes (OR = 2.00; CI 1.86-2.18, P < 0.01), hyperlipidaemia (OR = 1.50; CI 1.39-1.61, P < 0.01), smoking (OR = 1.10; CI 1.03-1.18, P = 0.06) and CCS class IV symptoms (OR = 1.43; CI 1.34-1.53, P < 0.01). CCS Class IV angina was a stronger predictor of severe CAD amongst women compared with men (women OR = 1.82; CI 1.61-2.04 vs. men OR = 1.28; CI 1.18-1.39, P < 0.01). CONCLUSIONS: Women referred for first diagnostic angiography have lower rates of severe CAD compared with men across all ages. Whilst conventional risk factors, age, sex, diabetes, smoking and hyperlipidaemia are primary determinants of CAD amongst women and men, CCS Class IV angina is more likely to be associated with severe CAD in women than men.

Ozone and temperature trends associated with the 11-year solar cycle.

Evidence is presented which suggests that trends in the ozone concentration and stratospheric temperature, reported between the early 1960's and 1976, are to a large extent due to solar ultraviolet flux variability associated with the 11-year solar cycle. Radiative-convective-photochemical simulations of ozone and temperature variations have been made with a solar ultraviolet flux variability model. Results for temperatures and ozone concentrations, when compared with published data, show good agreement.

Incremental detection of coronary artery disease by assessment of non-calcified plaque on coronary CT angiography.

AIM: The purpose of this study was to evaluate the improved assessment of coronary atherosclerotic plaque burden by measurement of non-calcified plaque in addition to calcified plaque using CT coronary angiography (CTA). MATERIALS AND METHODS: Low to intermediate-risk outpatients with suspected coronary artery disease were prospectively recruited. Patients underwent CTA and calcium scoring in addition to invasive angiography. The presence of plaque (calcified, non-calcified, and mixed) was analysed on a per segment basis (percentage of segments with disease) with stratification by calcium score (CS). RESULTS: Seventy-six patients were enrolled of whom 30 had a CS of 0, 26 had a CS of 1-200, and 20 had a CS of >200. One thousand, one hundred and two segments were analysed using CTA and invasive angiography. The prevalence of segments with calcified or mixed plaque was 3.1% (n=13) for a CS of 0, 15.1% (n=57) for a CS of 1-200, and 50% (n=142) for a CS of >200 (all p<0.0001). The proportion of segments with non-calcified plaque alone was low and similar among the three groups: 5.4% (n=23; CS=0), 8.2% (n=32; CS=1-200), and 8.6% (n=25; CS= >200), (CS=0 versus CS= >200; p=0.04, others p=ns). The relative increase in diseased segments by additional assessment of non-calcified plaque was greatest for patients with a CS of 0 (173%) versus a CS of 1-200 (55%), and a CS of >200 (17%). CONCLUSION: CTA offers increased relative incremental detection of non-calcified plaque, particularly in those with negative CS; however, the absolute detection of non-calcified plaque in those with negative CS is low. The prognostic significance of non-calcified plaque for the prediction of cardiac events, particularly in patients with low CS, requires continued study.

Massage therapy in the workplace: reducing employee strain and blood pressure.

AIM: Assess the effects of workplace-based massage therapy on physiological and psychological outcomes. METHODS: We used afield experiment in which 28 participants were randomly assigned into either an experimental (n = 14) or control (n = 14) group. The experimental group received weekly massage treatments at work for a four week period while the control group did not. RESULTS: Both strain and blood pressure were significantly reduced during treatment for the experimental group but not for the control group. CONCLUSIONS: This study provides initial support for the effectiveness of workplace-based massage therapy as part of a comprehensive workplace health strategy.

Myosin IIA and formin dependent mechanosensitivity of filopodia adhesion.

Filopodia, dynamic membrane protrusions driven by polymerization of an actin filament core, can adhere to the extracellular matrix and experience both external and cell-generated pulling forces. The role of such forces in filopodia adhesion is however insufficiently understood. Here, we study filopodia induced by overexpression of myosin X, typical for cancer cells. The lifetime of such filopodia positively correlates with the presence of myosin IIA filaments at the filopodia bases. Application of pulling forces to the filopodia tips through attached fibronectin-coated laser-trapped beads results in sustained growth of the filopodia. Pharmacological inhibition or knockdown of myosin IIA abolishes the filopodia adhesion to the beads. Formin inhibitor SMIFH2, which causes detachment of actin filaments from formin molecules, produces similar effect. Thus, centripetal force generated by myosin IIA filaments at the base of filopodium and transmitted to the tip through actin core in a formin-dependent fashion is required for filopodia adhesion.

Long term follow-up results of 1 year MDT in MB leprosy patients treated with standard MDT + once a month Minocycline and Ofloxacin.

BACKGROUND: This study was initiated in consultation with the National Leprosy Eradication Programme (NLEP) in mid nineties to try new treatment regimens for leprosy which were more robust in terms of control of reactions, long term relapses, operationally easier to undertake and feasible in field conditions. It was also envisaged to see if the addition of newer bactericidal drugs would be beneficial. OBJECTIVES: (i) To test the feasibility, safety and response of the patients to the new regimen. (ii) To observe the incidence of reactions during and after stoppage of therapy, for a period of 8-10 years after release from treatment. MATERIALS AND METHODS: A total of one hundred skin smear positive MB patients (15 LL, 35 BL and 50 BB) patients were included in this study. All the patients received the standard MDT + once a month supervised 100 mg of Minocycline and 400 mg of Ofloxacin for 12 months during the treatment phase. Thereafter, the treatment was stopped in all the patients which were followed-up on placebo (B complex tablets). Of these, 70 patients completed the treatment schedule of one year therapy and the post treatment follow-up of 9 to 10 years. RESULTS: All the patients tolerated the drugs well. The clinical response of the patients to the treatment was very good of which 32.85% of cases had history of reactions before starting treatment. During treatment, the incidence of reactions increased marginally to 38.5%, but these were easily controlled with concurrent administration of steroids. After completion of treatment the incidence was much less i.e. 10% and 3% after 1 and 2 years of post treatment follow-up respectively. The overall relapse rate is 5.7% (4/70) with an incidence density of 0.05/100 patient years. Relapses were confirmed by clinical, bacteriological, molecular biological (rRNA probes and 36 kD targeting PCR) as well as ATP bioluminescence. The relapsed patients presented with the appearance of new lesions, slit-skin smears were again found to become positive after becoming negative. Three of the four cases who relapsed had the initial mean BI of 2 to 2.9+ whereas one had the initial mean BI of 1.5+. Also, 2 of the 4 relapsed patients had positive PCR signals at the time of stoppage of treatment. CONCLUSION: The addition of Minocycline and Ofloxacin to the standard FDT has been observed to be a well tolerated. Overall as of now, the incidence of reactions observed with the newer treatment regimen is found to be significantly lower than that of 2 years fixed duration MB-MDT. The efficacy of this regimen regarding bacteriological clearance and relapse rates could not be compared due to non-availability of the results of experience with standard 1 year MDT regimen. However, this regimen appears to be operationally feasible and safe for the users.

HEF1 is a necessary and specific downstream effector of FAK that promotes the migration of glioblastoma cells.

The highly invasive behavior of glioblastoma cells contributes to the morbidity and mortality associated with these tumors. The integrin-mediated adhesion and migration of glioblastoma cells on brain matrix proteins is enhanced by stimulation with growth factors, including platelet-derived growth factor (PDGF). As focal adhesion kinase (FAK), a nonreceptor cytoplasmic tyrosine kinase, has been shown to promote cell migration in various other cell types, we analysed its role in glioblastoma cell migration. Forced overexpression of FAK in serum-starved glioblastoma cells plated on recombinant (rec)-osteopontin resulted in a twofold enhancement of basal migration and a ninefold enhancement of PDGF-BB-stimulated migration. Both expression of mutant FAK(397F) and the downregulation of FAK with small interfering (si) RNA inhibited basal and PDGF-stimulated migration. FAK overexpression and PDGF stimulation was found to increase the phosphorylation of the Crk-associated substrate (CAS) family member human enhancer of filamentation 1 (HEF1), but not p130CAS or Src-interacting protein (Sin)/Efs, although the levels of expression of these proteins was similar. Moreover downregulation of HEF1 with siRNA, but not p130CAS, inhibited basal and PDGF-stimulated migration. The phosphorylated HEF1 colocalized with vinculin and was associated almost exclusively with 0.1% Triton X-100 insoluble material, consistent with its signaling at focal adhesions. FAK overexpression promoted invasion through normal brain homogenate and siHEF1 inhibited this invasion. Results presented here suggest that HEF1 acts as a necessary and specific downstream effector of FAK in the invasive behavior of glioblastoma cells and may be an effective target for treatment of these tumors.

Limb salvage surgery complimented by customised mega prostheses for malignant fibrous histiocytomas of bone.

PURPOSE: To assess functional and oncological outcomes of patients with malignant fibrous histiocytomas of bone, after limb salvage surgery complimented by a customised prosthesis. METHODS: Between May 1991 and December 2002, 15 men and 5 women (mean age, 42 years) with histologically proven malignant fibrous histiocytoma of bone underwent treatment involving limb salvage surgery complimented by a customised mega prosthesis. Most of the tumours were stage II according to the Enneking system, and located around the knee. Wide resection margins were achieved in 18 patients. RESULTS: Following a mean follow-up of 58 months, 4 patients underwent amputation for local recurrence and 5 died of the disease. Two patients had prosthesis fractures; revision of the prosthesis was carried out in one. The functional result was excellent in 5 and good in 9 patients. The Kaplan-Meier 5-year survival rates of the patients treated without chemotherapy and with chemotherapy were 50% and 76%, respectively. CONCLUSION: Limb salvage surgery with chemotherapy is a viable treatment option for patients with malignant fibrous histiocytoma of bone. It achieves higher survival rates than resection alone. Such therapy improves quality of life and provides a useful and functional limb.

A survey of doctors at a UK teaching hospital to assess understanding of recent changes to consent law.

BACKGROUND: The UK Supreme Court recently ruled that when consenting patients for treatments or procedures, clinicians must also discuss any associated material risks. We surveyed medical staff at a large UK teaching hospital in order to ascertain knowledge of consent law and current understanding of this change. MATERIALS AND METHODS: Email survey sent to medical staff in all specialities at Norfolk and Norwich University Hospital in February 2016. RESULTS: 245 responses (141 Consultants and 104 junior doctors, response rate 32%). 82% consent patients for procedures at least monthly and 23% daily. 31% were not familiar with the concept of material risk. 35% were familiar with the recent change in consent law, 41% were not. 18% were "very uncertain" and 64% "a little uncertain" that their consenting process meets current legal requirements. >92% think that landmark cases and changes in law should be discussed through professional bodies and circulated better locally. CONCLUSION: The majority were not familiar with the concept of material risk and recent legal changes. A majority were not confident that their practice meets current requirements, suggesting that recent changes in consent law may not be widely understood at this hospital. We suggest more guidance and education may be necessary than is currently available. Increased understanding of recent changes to consent law will reduce the risk taken by NHS trusts and offer patients a service compliant with Supreme Court guidance.

A mononuclear iron carbonyl complex [Fe(µ-bdt)(CO)2(PTA)2] with bulky phosphine ligands: a model for the [FeFe] hydrogenase enzyme active site with an inverted redox potential.

A mononuclear hexa-coordinated iron carbonyl complex [Fe(µ-bdt)(CO)2(PTA)2] 1 (bdt = 1,2-benzenedithiolate; PTA = 1,3,5-triaza-7-phosphaadamantane) with two bulky phosphine ligands in the trans position was synthesized and characterized by X-ray structural analysis coulometry data, FTIR, electrochemistry and electronic structure calculations. The complex undergoes a facilitated two-electron reduction 1/12- and shows an inverted one-electron reduction for 1/1- at higher potentials. Electrochemical investigations of 1 are compared to the closely related [Fe(bdt)(CO)2(PMe3)2] compound. A mechanistic suggestion for the hydrogen evolution reaction upon proton reduction from acid media is derived. The stability of 1 in both weak and strong acids is monitored by cyclic voltammetry.

Abdominal wall ectopic testis torsion mimicking a Spigelian hernia in an adult.

We report an unusual case of an ectopic testis identified in a 37-year-old man presenting with acute severe right iliac fossa pain and an irreducible mass. Initially diagnosed as a Spigelian hernia, computed tomography and ultrasonography identified the presence of an ectopic testis in the abdominal wall. Interparietal testicular ectopia is an extremely rare condition. We present and discuss the first case in the literature of an ectopic testis located between the internal and external oblique muscle layers of the anterior abdominal wall in an adult.

Nuclear translocation and DNA-binding activity of NFKB (NF-kappaB) after exposure of human monocytes to pulsed ultra-wideband electromagnetic fields (1 kV/cm) fails to transactivate kappaB-dependent gene expression.

The objective of this study was to investigate whether exposure of human monocytes to a pulsed ultra-wideband electromagnetic field (EMF) of 1 kV/cm average peak power triggers a signaling pathway responsible for the transcriptional regulation of NFKB (NF-kappaB)-dependent gene expression. Human Mono Mac 6 (MM6) cells were exposed intermittently to EMF pulses for a total of 90 min. The pulse width was 0.79+/-0.01 ns and the pulse repetition rate was 250 pps. The temperature of the medium was maintained at 37 degrees C in both sham- and EMF-exposed flasks. Total NFKB DNA-binding activity was measured in the nuclear extracts by the electrophoretic mobility shift assay. Cells exposed to the EMFs and incubated for 24 h postexposure showed a 3.5+/-0.2-fold increase in the NFKB DNA-binding activity. Since activation of NFKB was observed, the possibility of kappaB-dependent gene expression in response to exposure to the EMFs was investigated using NFKB signal-specific gene arrays. The results revealed no difference in the NFKB-dependent gene expression profiles at 8 or 24 h postexposure, indicating that activated NFKB does not lead to the differential expression of kappaB-dependent target genes. To determine whether the absence of the kappaB-dependent gene expression was due to compromised transcriptional regulation of NFKB, the functional activity of NFKB was examined in cells transiently transfected with Mercury Pathway constructs containing 4x NFKB binding sites associated either with the luciferase reporter system or a control vector. Pulsed EMF exposure did not induce NFKB-driven luciferase activity in these cells, indicating that the activation of NFKB at 24 h after the 1 kV/cm EMF exposure is functionally inactive. From these results, it is clear that the EMF-induced NFKB activation is only a transient response, with minimal or no downstream effect.

A Case of Hepatopulmonary Syndrome.

We report the case of a 52-year-old female, a known case of Chronic Liver Disease with portal hypertension. She presented with dyspnoea, platypnoea, melena, cyanosis, clubbing and orthodeoxia. She had oesophageal varices and splenomegaly indicating portal hypertension. Her arterial blood gas revealed hypoxaemia and orthodeoxia. From this clinical background and investigation, a diagnosis of hepatopulmonary syndrome was made. Patient was managed conservatively as she was not willing for liver transplantation.

Protection against oxidative protein damage induced by metal-catalyzed reaction or alkylperoxyl radicals: comparative effects of melatonin and other antioxidants.

Melatonin is a well-known hydroxyl radical (*OH) scavenger that protects DNA and lipids from free radical attack. In this paper, we studied the ability of melatonin to prevent oxidative damage to bovine serum albumin (BSA) induced by two different paradigms: the metal-catalyzed oxidation (MCO) induced by Cu(2+)/H(2)O(2) and the alkoxyl and alkylperoxyl radicals formed by the azo initiator 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH, 40 mM). The protective effects of melatonin were compared with 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox), glutathione (GSH), ascorbate, 3,4',5-trihydroxy-trans-stilbene (resveratrol, 0.1 microM-4 mM) and mannitol (50 microM-100 mM). Melatonin efficiently prevented protein modification induced by both models, as assayed by polyacrylamide gel electrophoresis and carbonyl content. Both trolox and ascorbate had an obvious pro-oxidant effect in the Cu(2+)/H(2)O(2) model, whereas both prevented BSA damage induced by AAPH. In the MCO model, the efficacy of GSH in terms of protein protection was higher than melatonin at relatively high concentrations (250 microM-4 mM); however, at lower concentrations (50-250 microM), the efficacy of melatonin was superior to GSH. D-Mannitol (50 microM-100 mM) and resveratrol did not protect BSA from the site-specific damage induced by Cu(2+)/H(2)O(2). On the other hand, the relative protective efficiency in the AAPH model was melatonin approximately trolox>GSH>ascorbate.