An Overview of Rhinoplasty Practices: European Academy of Facial Plastic Surgery, Collaborative Cross-Sectional Study.

This collaborative European Academy of Plastic Surgery (EAFPS) study aimed to provide an overview of rhinoplasty practices, informing clinician and patient decision making. It is a multicenter cross-sectional study, reported as per Strengthening the Reporting of Observational Studies in Epidemiology guidelines. All EAFPS members were contacted via email, inviting them to participate. Members expressing an interest to participate were asked to anonymously complete a questionnaire, related to rhinoplasties that they performed as first/supervising surgeon over a period from January 1, 2019 to January 1, 2022. A descriptive analysis was performed. One hundred and fifteen surgeons submitted data on 41,259 rhinoplasties from 33 countries. Eighty percent of rhinoplasties were primary, and 20% were secondary. Thirty five percent of primary rhinoplasties were closed and 65% were open. Thirty one percent of primary rhinoplasties were for cosmetic indications, 11% functional and 58% were for both. Of the 8147 secondary rhinoplasties, 44% were closed and 56% were open. Thirty percent were for cosmetic indications, 11% functional, and 59% for both cosmetic and functional. Ninety-one percent of rhinoplasties were performed by ENT surgeons, 3% by plastic surgeons, 5% by maxillofacial surgeons, and 1% were dual (maxillofacial and ENT) trained. One-thousand seven-hundred thirty primary rhinoplasties underwent revision surgery (5%) and 102 secondary rhinoplasties underwent revision surgery (1%). The most commonly reported indications for revision surgery were dorsal asymmetry, nasal blockage, and dissatisfaction with nasal tip. Three percent of rhinoplasties underwent preoperative psychological assessment. To the authors knowledge, this is the largest published rhinoplasty dataset. This study provides an overview of rhinoplasty practices that can be used for benchmarking and to guide clinician and patient decision making. Psychological assessment of prerhinoplasty appears insufficient with higher levels recommended to minimize unsuccessful outcomes. This study showcases the power of collaborative research and may serve as a catalyst for future collaborative facial plastic surgery research.

Impaired motor inhibition in developmental coordination disorder.

This study aimed to evaluate the 'inhibitory deficit' hypothesis of developmental coordination disorder (DCD). We adopted a multifaceted approach, investigating two distinct, yet complimentary facets of motor inhibition: action restraint and action cancellation. This was achieved using carefully constructed versions of the 'Go/No-go' and 'Stop-signal' tasks, respectively. The sample comprised 11 young adults with DCD aged between 18 and 30 years of age and 11 typically developing, age-matched controls. Participants completed both the 'Go/No-go' and 'Stop-signal' tasks to assess action restraint and action cancellation respectively. Individuals with DCD were less efficient than their typically developing peers at performing both action restraint and action cancellation, indicated by significantly reduced action restraint efficiency index scores on the 'Go/No-go' task and a trend towards longer stop-signal reaction times on the 'Stop-signal' task. This work clarifies disparate evidence speaking to the integrity of action restraint in DCD and provides the first account of action cancellation in DCD using a purpose-built measure. In support of the inhibitory deficit hypothesis of DCD, our results suggest that young adults with DCD experience broad difficulties with engaging inhibitory mechanisms during motor behaviour.

Evaluation of the association between a single-nucleotide polymorphism of bone morphogenetic proteins 5 gene and risk of knee osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a chronic degenerative disorder probably affected by both genetic and environmental causes. Bone morphogenetic proteins (BMPs) are bone-derived factors that can induce new bone formation. Single-nucleotide polymorphisms (SNPs) of BMP5 gene alters the transcriptional activity of the BMP5 promoter that has been involved in OA susceptibility. This case-control study investigated the association of rs1470527 and rs9382564 SNP of BMP5 gene with susceptibility to knee OA (KOA). MATERIALS AND METHODS: A total of 499 cases with radiographic KOA and 458 age- and sex-matched healthy controls were enrolled. Venous blood samples were obtained from all the cases as well as controls for polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The genotype distribution for rs1470527 and rs9382564 SNP was significantly different in cases and controls (P < 0.0001). Within both the SNPs of BMP5 gene, genotype CT and TT were significantly (P < 0.0001) associated with KOA as compared to the CC genotype. T allele of both the studied SNP was significantly associated with KOA (P < 0.0001). The allele frequencies of rs1470527 were 0.56(T) and 0.44(C) in cases and 0.33(T) and 0.67(C) in controls and in rs9382564 were 0.57(C) and 0.43(T) in cases and 0.71(C) and 0.29(T) in controls. Further in relation with clinical severity of OA, we observed signification association of TT genotype with both visual analog scale (P < 0.0001) and Western Ontario and McMaster Universities score (P < 0.05). CONCLUSION: Our results indicate significant association of rs1470527 and rs9382564 polymorphism of BMP5 gene with KOA.

Association of interleukin-10 polymorphisms with chronic hepatitis C virus infection in a case-control study and its effect on the response to combined pegylated interferon/ribavirin therapy.

We conducted a case-control study involving 150 genotype 3 chronic hepatitis C virus (HCV) patients and 150 healthy controls to investigate the association of polymorphisms in the interleukin-10 (IL-10) gene with chronic HCV infection and the association of these polymorphic variants with the combination of pegylated interferon (Peg-IFN) and ribavirin therapy response. Our data revealed that the GG genotype of IL-10 -1082A/G exhibited significant association with genotype 3 chronic HCV infection compared to controls. Treatment response data also showed a significant increase in risk for the GG genotype of IL-10 -1082A/G in response-relapse patients or non-responder patients compared to sustained virological response patients. Further, a significant increase in risk was also revealed for the CC genotype of IL-10 -592A/C in response-relapse patients or non-responder patients compared to sustained virological response patients, suggesting a role of the GG genotype of IL-10 -1082A/G and CC genotype of IL-10 -592A/C in the treatment outcome of combined Peg-IFN/ribavirin therapy.

Evaluation of a service intervention to improve awareness and uptake of bowel cancer screening in ethnically-diverse areas.

BACKGROUND: Uptake of bowel cancer screening is lowest in London, in populations of lower socio-economic status, and in particular ethnic or religious groups. METHODS: We report on the evaluation of two interventions to improve uptake in an area including populations of low socio-economic status and considerable ethnic diversity. The interventions were face-to-face health promotion on bowel cancer screening at invitees' general practice and health promotion delivered by telephone only. Nine large general practices in East London were chosen at random to offer face-to-face health promotion, and nine other large practices to offer telephone health promotion, with 24 practices of similar size as comparators. Data at practice level were analysed by Mann-Whitney-Wilcoxon tests and grouped-logistic regression. RESULTS: There were 2034 invitees in the telephone intervention practices, 1852 in the face-to-face intervention practices and 5227 in the comparison practices. Median gFOBt kit uptake in the target population (aged 59-70) was 46.7% in the telephone practices, 43.8% in the face-to-face practices and 39.1% in the comparison practices. Significant improvements in the odds of uptake were observed following telephone intervention in both males (OR=1.39, 95% CI=1.20-1.61, P<0.001) and females (OR=1.49, 95% CI=1.29-1.73, P<0.001), while the face-to-face intervention mainly impacted uptake in males (OR=1.23, 95% CI=1.10-1.36), P<0.001) but did not lead to a significant increase in females (OR=1.12, 95% CI=0.96-1.29, P=0.2). CONCLUSIONS: Personally delivered health promotion improved uptake of bowel cancer screening in areas of low socio-economic status and high ethnic diversity. The intervention by telephone appears to be the most effective method.

Reduction in interval cancer rates following the introduction of two-view mammography in the UK breast screening programme.

BACKGROUND: The introduction of two-view mammography at incident (subsequent) screens in the National Health Service Breast Screening Programme (NHSBSP) has led to an increased number of cancers detected at screen. However, the effect of two-view mammography on interval cancer rates has yet to be assessed. METHODS: Routine screening and interval cancer data were collated from all screening programmes in the United Kingdom for women aged 50-64, screened between 1 April 2003 and 31 March 2005. Interval cancer rates were compared based on whether two-view mammography was in use at the last routine screen. RESULTS: The reduction in interval cancers following screening using two-view mammography compared with one view was 0.68 per 1,000 women screened. Overall, this suggests the introduction of two-view mammography at incident screen was accompanied by a 15-20% reduction in interval cancer rates in the NHSBSP. CONCLUSION: The introduction of two-view mammography at incident screens is associated with a reduction in incidence of interval cancers. This is consistent with previous publications on a contemporaneous increase in screen-detected cancers. The results provide further evidence of the benefit of the use of two-view mammography at incident screens.

A randomised trial of weekend and evening breast screening appointments.

BACKGROUND: There is a need to research interventions that improve access to and convenience of breast cancer screening services. METHODS: We conducted a randomised trial comparing invitations to out-of-hours appointments with standard office hour appointments. Women who were to be invited for routine breast screening were randomised (3 : 1 : 1 : 1) to one of these screening invitations: standard office hour appointment, office hour appointment with the option to change to an out-of-hours appointment, weekday evening appointment, or weekend appointment. RESULTS: A total of 9410 women were invited to an office hour, 3519 to an office hour with the option to change, 3271 to a weekday evening, and 3162 to a weekend appointment. The offer of an initial out-of-hours appointment was associated with a non-significant decrease in attendance rates (73.7% vs 74.1%). The highest attendance was observed in the group offered an initial office hour appointment with the option to change to out-of-hours (76.1% vs 73.3% for standard office hour, P=0.001), with 7% of invitees exercising the option to change. CONCLUSION: The optimum strategy for improving attendance at breast screening is to offer a traditional office hour appointment and including in the letter of invitation an option to change to an evening or weekend appointment if wished.

The genesis of the PM-JAY health insurance scheme in India: technical and political elements influencing a national reform towards universal health coverage.

Many countries are using health insurance to advance progress towards universal health coverage (UHC). India launched the Pradhan Mantri Jan Arogya Yojana (PM-JAY) health insurance scheme in 2018. We examine the political economy context around PM-JAY policy formulation, by examining the perspectives of policy stakeholders shaping decisions around the reform. More specifically, we focus on early policy design at the central (national) level. We use a framework on the politics of UHC reform proposed by Fox and Reich (The politics of universal health coverage in low- and middle-income countries: A framework for evaluation and action. J. Health Polit. Policy Law 2015;40:1023-1060), to categorize the reform into phases and examine the interactions between actors, institutions, interests, ideas and ideology which shaped reform decisions. We interviewed 15 respondents in Delhi between February and April 2019, who were either closely associated with the reform process or subject experts. The ruling centre-right government introduced PM-JAY shortly before national elections, drawing upon policy legacies from prior and state insurance schemes. Empowered policy entrepreneurs within the government focused discourse around ideas of UHC and strategic purchasing, and engaged in institution building leading to the creation of the National Health Authority and State Health Agencies through policy directives, thereby expanding state infrastructural and institutional power for insurance implementation. Indian state inputs were incorporated in scheme design features like mode of implementation, benefit package and provider network, while features like the coverage amount, portability of benefits and branding strategy were more centrally driven. These balanced negotiations opened up political space for a cohesive, central narrative of the reform and facilitated adoption. Our analysis shows that the PM-JAY reform focused on bureaucratic rather than ideological elements and that technical compromises and adjustments accommodating the interests of states enabled the political success of policy formulation. Appreciating these politics, power and structural issues shaping PM-JAY institutional design will be important to understand how PM-JAY is implemented and how it advances UHC in India.

Combining ability, heterosis and performance of grain yield and content of Fe, Zn and protein in bread wheat under normal and late sowing conditions.

Wheat (Triticum aestivum L.) is inherently low in protein content, Zn and Fe. Boost yield gains have unwittingly reduced grain Zn and Fe, which has had negative impacts on human health. The aim of this study was to understand the inheritance of grain yield per plant and grain Fe, Zn, and protein concentrations in bread wheat (Triticum aestivum L.) under normal and late sown conditions. Half diallel crosses were performed using 10 parents. The crosses and parents were evaluated in replicated trials for the two conditions, to assess the possibility of exploiting heterosis to improve micronutrient contents. The per se performance, heterosis, combining ability, and genetic components were estimated for different characters in both environments. The results revealed that hybrid GW 451 × GW 173 exhibited better parent heterosis (BPH) and standard heterotic effects (SH) in all environments. In both sowing conditions, the general combining ability (GCA) effects of poor × poor parents also showed high specific combining ability (SCA) effects of hybrids for both the micronutrients and protein contents. However, σ2A/σ2D greater than unity confirmed the preponderance of additive gene action for protein content, and GW 173 was identified as a good general combiner for these characteristics under both environments. SCA had positive significant (P < 0.001) correlations with BPH, SH1, SH2, and the phenotype for yield component traits and grain protein, Fe, and Zn concentrations in both conditions. A supplementary approach for biofortifying wheat grainis required to prevent malnutrition.

Effect of plastic-covered ultrasonic scalers on titanium implant surfaces.

OBJECTIVES: Maintaining oral health around titanium implants is essential. The formation of a biofilm on the titanium surface will influence the continuing success of the implant. These concerns have led to modified ultrasonic scaler instruments that look to reduce implant damage while maximising the cleaning effect. This study aimed to assess the effect of instrumentation, with traditional and modified ultrasonic scalers, on titanium implant surfaces and to correlate this with the oscillations of the instruments. MATERIALS AND METHODS: Two ultrasonic insert designs (metallic TFI-10 and a plastic-tipped implant insert) were selected. Each scaler probe was scanned using a scanning laser vibrometer, under loaded and unloaded conditions, to determine their oscillation characteristics. Loads were applied against a titanium implant (100g and 200 g) for 10 s. The resulting implant surfaces were then scanned using laser profilometry and scanning electron microscopy (SEM). RESULTS: Insert probes oscillated with an elliptical motion with the maximum amplitude at the probe tip. Laser profilometry detected defects in the titanium surface only for the metallic scaler insert. Defect widths at 200 g high power were significantly larger than all other load/power conditions (P<0.02). Using SEM, it was observed that modifications to the implant surface had occurred following instrumentation with the plastic-tipped insert. Debris was also visible around the defects. CONCLUSIONS: Metal scalers produce defects in titanium implant surfaces and load and power are important factors in the damage caused. Plastic-coated scaler probes cause minimal damage to implant surfaces and have a polishing action but can leave plastic deposits behind on the implant surface.

Sensitivity analysis of water quality for Delhi stretch of the River Yamuna, India.

Simulation models are used to aid the decision makers about water pollution control and management in river systems. However, uncertainty of model parameters affects the model predictions and hence the pollution control decision. Therefore, it often is necessary to identify the model parameters that significantly affect the model output uncertainty prior to or as a supplement to model application to water pollution control and planning problems. In this study, sensitivity analysis, as a tool for uncertainty analysis was carried out to assess the sensitivity of water quality to (a) model parameters (b) pollution abatement measures such as wastewater treatment, waste discharge and flow augmentation from upstream reservoir. In addition, sensitivity analysis for the "best practical solution" was carried out to help the decision makers in choosing an appropriate option. The Delhi stretch of the river Yamuna was considered as a case study. The QUAL2E model is used for water quality simulation. The results obtained indicate that parameters K(1) (deoxygenation constant) and K(3) (settling oxygen demand), which is the rate of biochemical decomposition of organic matter and rate of BOD removal by settling, respectively, are the most sensitive parameters for the considered river stretch. Different combinations of variations in K(1) and K(2) also revealed similar results for better understanding of inter-dependability of K(1) and K(2). Also, among the pollution abatement methods, the change (perturbation) in wastewater treatment level at primary, secondary, tertiary, and advanced has the greatest effect on the uncertainty of the simulated dissolved oxygen and biochemical oxygen demand concentrations.

Changes in the provision of undergraduate ENT clinical placements across the UK in response to the coronavirus disease 2019 pandemic.

OBJECTIVE: This study aimed to report the changes made to ENT placements across the UK in response to the pandemic and their impact on student experience. METHODS: A questionnaire eliciting how ENT placements were provided before and after coronavirus disease 2019 was disseminated amongst Student and Foundation Doctors in Otolaryngology representatives. RESULTS: Thirty-eight respondents from 27 medical schools across the UK completed the survey (response rate of 90 per cent). Twenty-nine of the 38 respondents (76 per cent) reported a change in ENT placements in response to the pandemic. Six of the 38 students (16 per cent) remained satisfied with their ENT placements, as compared to 12 students prior to the pandemic (32 per cent). CONCLUSION: There is considerable variability in how medical schools responded to the pandemic. Most medical schools placed students into smaller groups, with less direct contact in the hospital. These changes resulted in lower student satisfaction. The increased emphasis on e-learning underscores the need for high quality e-learning materials to promote learning throughout the pandemic and in the future.

Bacterial localization and viability assessment in human ex vivo dentinal tubules by fluorescence confocal laser scanning microscopy.

AIM: To develop a convenient method for the localization and quantification of live and dead bacteria in human ex vivo mineralized dentinal tubules. METHODOLOGY: The roots from human single-rooted teeth (n = 12) were infected with Enterococcus faecalis V583 and either treated with calcium hydroxide paste or left untreated; six control roots were uninoculated and untreated. Following further incubation, roots were stained with fluorescent DNA-binding reagents, washed thoroughly, sectioned and examined by confocal laser scanning microscopy. Computer-assisted determinations of fluorescence (bacterial viability) were compared statistically. RESULTS: Bacteria were distributed in the tubules throughout the length of the roots but tubule penetration distance was slightly reduced in the apical sections. There was no significant difference in bacterial tubule penetration between roots from different teeth and small standard deviations indicated reproducibility appropriate for experimental application. Following treatment with calcium hydroxide paste, live and dead bacteria were readily distinguishable by contrasting green and red fluorescence. Bacterial viability determinations amongst roots treated in the same way were not significantly different, and the small standard deviation is commensurate with experimental application. CONCLUSIONS: Fluorescent viability staining is a convenient, accurate and reproducible method for localizing and quantifying live and dead bacteria in human ex vivo mineralized dentinal tubules.

Outcomes of repeat two-stage exchange hip arthroplasty for prosthetic joint infection.

AIMS: The increasing infection burden after total hip arthroplasty (THA) has seen a rise in the use of two-stage exchange arthroplasty and the use of increasingly powerful antibiotics at the time of this procedure. As a result, there has been an increase in the number of failed two-stage revisions during the past decade. The aim of this study was to clarify the outcome of repeat two-stage revision THA following a failed two-stage exchange due to recurrent prosthetic joint infection (PJI). PATIENTS AND METHODS: We identified 42 patients who underwent a two-stage revision THA having already undergone at least one previous two stage procedure for infection, between 2000 and 2015. There were 23 women and 19 men. Their mean age was 69.3 years (48 to 81). The outcome was analyzed at a minimum follow-up of two years. RESULTS: A satisfactory control of infection and successful outcome was seen in 26 patients (57%). There therefore remained persistent symptoms that either required further surgery or chronic antibiotic suppression in 16 patients (38%). One-third of patients had died by the time of two years' follow-up. CONCLUSION: The rate of failure and complication rate of repeat two-stage exchange THA for PJI is high and new methods of treatment including host optimization, immunomodulation, longer periods between stages, and new and more powerful forms of antimicrobial treatment should be investigated. Cite this article: Bone Joint J 2019;101-B(6 Supple B):110-115.

An alternative mantle irradiation technique using 3D CT- based treatment planning for female patients with Hodgkin's disease.

PURPOSE: For female patients, radiotherapy treatment for Hodgkin's disease invariably results in the irradiation of breast tissue that may lead to radiation induced secondary cancers. The risk for secondary breast cancer is correlated with dose. We have developed a technique in an attempt to increase breast sparing during mantle field irradiation for female patients. MATERIAL AND METHODS: To minimize the irradiated breast volume, a virtual simulation technique making use of a Styrofoam breast immobilization board has been developed whereby the patient lies prone with the breasts positioned in grooves within the board. The breast position is adjusted using Styrofoam wedges, and breast placement is verified using an AP CT-pilot view. A CT scan of the neck and thoracic regions is taken, and the lymph nodes, breast volume and critical structures are outlined. Virtual simulation of the mantle fields (typically AP/PA isocentric beams) is performed, and beam blocks are drawn on the digitally reconstructed radiographs (DRR) generated by the virtual simulation package. The shielding is designed to allow adequate margins around the lymph nodes while maximizing shielding of the lung and breast tissues. The para-aortic fields are also easily determined through virtual simulation, where multi-planar reconstructions (MPR) and 3D renderings of the patient's CT data are used to determine the field limits and beam gaps. In addition to allowing for the geometric optimization of the positioning of the breasts under the lung shields, the virtual simulation technique provides the necessary information for a 3D dosimetric analysis, including dose-volume histograms (DVHs) of the irradiated breast volume. RESULTS: The 3D breast sparing technique was qualitatively and quantitatively compared to non-CT-based techniques and other 3D techniques currently available to assess the protection of the breasts. In a preliminary analysis, virtual simulation images (DRRs, 3D rendering and multi-planar reconstruction) demonstrated the advantage of using the breast sparing technique. A further analysis of DVHs showed a reduction of at least 50% in the volume of breast tissue irradiated when using the breast positioning board and virtual simulation as compared to the conventional simulation techniques where a breast immobilization board was not used. CONCLUSIONS: The use of a breast immobilization board and of a virtual simulation technique is recommended for the planning and treatment of female patients with Hodgkin's disease. DVH analysis has shown that this leads to a decrease in the volume of breast irradiated. It is hoped that this approach will reduce the risk of secondary breast malignancies in female patients with Hodgkin's disease.

Mitochondrial ATPase: a target for paracetamol-induced hepatotoxicity.

We examined the effect of paracetamol treatment (650 mg/kg) on the function of ATPase from rat hepatic mitochondria. The drug treatment caused an overall 35% decrease in ATPase activity, with a complete loss of the high affinity component as determined by substrate kinetic studies. The Km for the intermediate and low affinity components decreased by about 30% without change in Vmax, which may represent a compensatory mechanism. The drug treatment also resulted in a dramatic decrease in the phase transition temperature by about 19 degrees C without affecting the energies of activation of the enzyme. Mitochondrial total phospholipid content increased significantly with a reciprocal decrease in the cholesterol content. The total phospholipid/cholesterol molar ration increased by 50% after paracetamol treatment. However, phospholipid composition (as % of total) of the mitochondria was unaltered.

Visual prognostic value of the pattern electroretinogram in chiasmal compression.

BACKGROUND/AIMS: The visual loss associated with compression of the optic chiasm by pituitary tumours may be transient or permanent, possibly related to the extent of irreversible retrograde degeneration to the retinal ganglion cells. The pattern electroretinogram (PERG) N95 component is thought to rise in relation to retinal ganglion cell function and hence may be a potential prognostic indicator for visual function following decompressive surgery. METHODS: The notes and electrodiagnostic records of 72 eyes from 36 patients with chiasmal compression were retrospectively analysed. RESULTS: The postoperative change in visual field was found to be associated with the PERG N95:P50 ratio (p=0.01). Improvement in visual field was shown by a greater proportion of eyes with a normal N95:P50 ratio (65%) than with an abnormal ratio (27%). No change in visual field occurred in 26% of the eyes with a normal N95:P50 ratio compared with 67% of those with an abnormal ratio. Only 8% of eyes showed a worsening of visual field following surgery, in similar proportions for eyes with normal and abnormal N95:P50 ratios. There was no significant relationship with visual acuity. CONCLUSION: The PERG is a useful visual prognostic indicator in the preoperative assessment of chiasmal compression.

Effect of di(2-ethylhexyl)phthalate (DEHP) on spermatogenesis in adult rats.

Oral administration of di(2-ethylhexyl)phthalate (DEHP) in doses of 250, 500, 1000 and 2000 mg/kg to adult rats for 15 days caused a significant dose dependent decrease in the sperm count of the epididymal spermatozoa. The activity of gamma-glutamyl transpeptidase (gamma GT) and lactate dehydrogenase (LDH) was significantly increased in the animals of the treated groups. An increase in the activity of beta-glucuronidase and decrease in the activity of acid phosphatase was also observed at the highest dose of DEHP. The activity of sorbitol dehydrogenase (SDH) was found to be decreased in the animals exposed to 1000 and 2000 mg/kg of DEHP. These results suggest that DEHP can affect spermatogenesis by altering the activities of the enzymes responsible for the maturation of sperms. The reduced number of sperms may be responsible for the antifertilic effects of DEHP.

Cytochrome P450 2E1 dependent catalytic activity and lipid peroxidation in rat blood lymphocytes.

To investigate the similarities in the catalytic activity of blood lymphocyte P450 2E1 in blood lymphocyte with the liver isoenzyme, NADPH dependent lipid peroxidation and activity of N-nitrosodimethyamine demethylase (NDMA-d) was studied in rat blood lymphocytes. Blood lymphocytes were found to catalyse NADPH dependent (basal) lipid peroxidation and demethylation of N-nitrosodimethylamine (NDMA). Pretreatment with ethanol or pyrazole or acetone resulted in significant increase in the NADPH dependent lipid peroxidation and the activity of NDMA-d in blood lymphocytes and liver microsomes. In vitro addition of CCl(4) to the blood lymphocytes isolated from control or ethanol pretreated rats resulted in an increase in the NADPH dependent lipid peroxidation. Significant inhibition of the basal and CCl(4) supported NADPH dependent lipid peroxidation and NDMA-d activity in blood lymphocytes isolated from control or ethanol pretreated rats by dimethyl formamide or dimethyl sulfoxide or hexane, solvents known to inhibit P450 2E1 catalysed reactions in liver and anti- P450 2E1, have indicated the role of P450 2E1 in the NADPH dependent lipid peroxidation in rat blood lymphocytes. The data indicating similarities in the NADPH dependent lipid peroxidation and NDMA-d activity in blood lymphocyte with the liver microsome have provided evidence that blood lymphocyte P450 2E1 could be used as a surrogate to monitor and predict hepatic levels of the enzyme.

Cytochrome P450 1A1 (CYP1A1) in blood lymphocytes evidence for catalytic activity and mRNA expression.

Studies initiated to characterise the catalytic activity and expression of CYP1A1 in rat blood lymphocytes revealed significant activity of 7-ethoxyresorufin-O-deethylase (EROD) in rat blood lymphocytes. Pretreatment with 3-methylcholanthrene (MC) and beta-naphthoflavone (NF) resulted in significant induction in the activity of lymphocyte EROD suggesting that like the liver enzyme, EROD activity in lymphocytes is inducible and is mediated by the MC inducible isoenzymes of P450. The increase in the activity of EROD was associated with a significant increase in the apparent Vmax and affinity of the substrate towards EROD. That this increase in the activity of EROD could be primarily due to the increase in the expression of CYP1A1 isoenzymes was demonstrated by RT-PCR and western immunoblotting studies indicating an increase in the expression of CYP1A1 in blood lymphocytes after MC pretreatment. Significant inhibition in the EROD activity of MC induced lymphocyte by anti-CYP1A1/1A2 and alpha-naphthoflavone further provided evidence that the CYP1A1/1A2 isoenzymes are involved in the activity of EROD in blood lymphocytes. The data indicating similarities in the regulation of CYP1A1 in blood lymphocytes with the liver isoenzyme suggests that factors which may affect expression of CYP1A1 in liver may also affect expression in blood lymphocytes and that blood lymphocytes could be used as a surrogates for studying hepatic expression of the xenobiotic metabolising enzymes.