Chrysin ameliorates ANTU‐induced pulmonary edema and pulmonary arterial hypertension via modulation of VEGF and eNOs

Alpha‐naphthylthiourea (ANTU), a rodenticide induces lung toxicity. Chrysin a flavonoid possesses antioxidant, anti‐inflammatory, and antihypertensive potential. The aim of this study was to evaluate the efficacy of chrysin against ANTU‐induced pulmonary edema (PE) and pulmonary arterial hypertension (PAH) in laboratory rats. Sprague‐Dawley rats were used to induce PE (ANTU, 10 mg/kg, ip) and PAH (ANTU, 5 mg/kg, ip, 4 weeks). Animals were treated with chrysin (10, 20, and 40 mg/kg) and various biochemical, molecular, and histological parameters were evaluated. Acute administration of ANTU induces PE revealed by significant (P < 0.05) increase in relative lung weight, pleural effusion volume, lung edema, bronchoalveolar lavage fluid cell counts, total protein, 5‐hydroxytryptamine (5‐HT), lactate dehydrogenase (LDH), and γ‐glutamyl transferase (GGT), whereas pretreatment with chrysin (20 and 40 mg/kg, ip) significantly (P < 0.05) attenuated these ANTU‐induced biochemical and histological alterations. Repeated administration of ANTU caused induction of PAH evaluated by significant (P < 0.05) alterations in electrocardiographic, hemodynamic changes, and left ventricular function, whereas chrysin (20 and 40 mg/kg, p.o.) treatment significantly (P < 0.05) attenuated these alterations. ANTU‐induced hematological and serum biochemical (aspartate transaminase, alanine transaminase, LDH, and creatinine kinase MB) alterations were significantly (P < 0.05) inhibited by chrysin. It also significantly (P < 0.05) decreased elevated levels of oxido‐nitrosative stress in the right ventricle (RV) and lung. Chrysin significantly (P < 0.05) attenuated downregulated endothelial nitric oxide synthase and upregulated vascular endothelial growth factor messenger RNA and protein expressions both in the RV and pulmonary artery. Chrysin inhibited ANTU‐induced PE and PAH via modulation of inflammatory responses (5‐HT, LDH, and GGT), oxido‐nitrosative stress, and VEGF and eNOs levels.     

Screening for colorectal cancer.

In the United Kingdom there are almost 31,000 new cases of colorectal cancer each year and nearly 20,000 deaths. It is the second most common cause of all deaths from cancer in the United Kingdom. The efficacy of screening with faecal occult blood tests to detect and treat tumours at an early stage, and thereby to reduce mortality, is currently being assessed in several randomised controlled trials. In general, faecal occult blood tests have a low sensitivity and only moderate levels of uptake among the population invited for screening. Until the studies in Denmark, Sweden, and Nottingham report their findings, there is no case for providing such screening routinely to an asymptomatic population. Detecting and removing premalignant adenomas by flexible sigmoidoscopy could be more effective than detecting early localised, asymptomatic cancers in reducing deaths from colorectal cancer. It is estimated that screening people at about the age of 60 by a single flexible sigmoidoscopy examination with appropriate colonoscopic surveillance could prevent 5500 cases of colorectal cancer and 3500 deaths in the United Kingdom each year. A randomised controlled trial to confirm these observations should be seen as a priority.     

Sporadic Creutzfeldt-Jakob disease in the United Kingdom: analysis of epidemiological surveillance data for 1970-96.

OBJECTIVE: To identify changes in the occurrence of Creutzfeldt-Jakob disease that might be related to the epidemic of bovine spongiform encephalopathy. DESIGN: Epidemiological surveillance of the United Kingdom population for Creutzfeldt-Jakob disease based on (a) referral of suspected cases by neurologists, neuropathologists, and neurophysiologists and (b) death certificates. SETTING: England and Wales during 1970-84, and whole of the United Kingdom during 1985-96. SUBJECTS: All 662 patients identified as sporadic cases of Creutzfeldt-Jakob disease. MAIN OUTCOME MEASURES: Age distribution of patients, age specific time trends of disease, occupational exposure to cattle, potential exposure to causative agent of bovine spongiform encephalopathy. RESULTS: During 1970-96 there was an increase in the number of sporadic cases of Creutzfeldt-Jakob disease recorded yearly in England and Wales. The greatest increase was among people aged over 70. There was a statistically significant excess of cases among dairy farm workers and their spouses and among people at increased risk of contact with live cattle infected with bovine spongiform encephalopathy. During 1994-6 there were six deaths from sporadic Creutzfeldt-Jakob disease in the United Kingdom in patients aged under 30. CONCLUSIONS: The increase in the incidence of sporadic Creutzfeldt-Jakob disease and the high incidence in dairy farmers in the United Kingdom may be unrelated to bovine spongiform encephalopathy. The most striking change in the pattern of Creutzfeldt-Jakob disease in the United Kingdom after the epidemic of bovine spongiform encephalopathy is provided by the incidence in a group of exceptionally young patients with a consistent and unusual neuropathological profile. The outcome of mouse transmission studies and the future incidence of the disease in the United Kingdom and elsewhere, will be important in judging whether the agent causing bovine spongiform encephalopathy has infected humans.     

Drug-Induced (Thalidomide) Malformations

Phocomelia (flipper-like limbs) has long been recognized as a rare malformation. Numerous cases of phocomelia and other congenital malformations have recently been reported in the United Kingdom, Australia, Europe and Canada in which the common factor appears to have been the administration of the hypnotic compound thalidomide during early pregnancy. Two additional cases of infants born with phocomelia, amelia and alimentary abnormalities are presented. In both of these cases the administration of thalidomide was initiated early during pregnancy (five to eight weeks after the last normal menstrual period) and maintained for several weeks. Thalidomide (alpha-phthalimido glutarimide) is related chemically to other glutarimides currently in clinical use. The possibility that these compounds and/or their metabolites may induce teratogenic effects warrants consideration. Emphasis is added to the view that caution should be exercised when prescribing new drugs.     

Is That Dog a Pit Bull? A Cross-Country Comparison of Perceptions of Shelter Workers Regarding Breed Identification

Bull breeds are commonly kept as companion animals, but the pit bull terrier is restricted by breed-specific legislation (BSL) in parts of the United States and throughout the United Kingdom. Shelter workers must decide which breed(s) a dog is. This decision may influence the dog's fate, particularly in places with BSL. In this study, shelter workers in the United States and United Kingdom were shown pictures of 20 dogs and were asked what breed each dog was, how they determined each dog's breed, whether each dog was a pit bull, and what they expected the fate of each dog to be. There was much variation in responses both between and within the United States and United Kingdom. UK participants frequently labeled dogs commonly considered by U.S. participants to be pit bulls as Staffordshire bull terriers. UK participants were more likely to say their shelters would euthanize dogs deemed to be pit bulls. Most participants noted using dogs' physical features to determine breed, and 41% affected by BSL indicated they would knowingly mislabel a dog of a restricted breed, presumably to increase the dog's adoption chances.     

Effect of pulmonary oedema induced by alpha-naphthylthiourea on synthesis of cyclo-oxygenase products in rat isolated lungs

Synthesis of COP (prostaglandins; PG and thromboxanes; Tx) from exogenous and endogenous arachidonic acid (AA) was studied in isolated perfused lungs from rats treated in vivo with a single dose of alpha-naphthylthiourea (ANTU; 10mg/kg;). Lung dry:wet weight ratios showed changes characteristic of oedema between 6 and 16h after ANTU. Bioassay of COP showed that COP synthesis from exogenous AA was raised above control values in lungs from rats treated with ANTU, reaching a maximum at 16h after treatment. By radioimmunoassay, the major increase was in 6-oxo-PGF1 alpha, with lesser effects on PGE2 and PGF2 alpha levels. Synthesis of bioassayable COP from endogenous AA induced by the calcium ionophore A23187 was increased as early as 2h after ANTU treatment and remained elevated up to 70h. In lungs 28h after ANTU, 6-oxo-PGF1 alpha release was greater than in normal lungs. These results show that in this model of pulmonary oedema, the potential for COP synthesis was increased. From the time course of this effect, increased COP synthesis was probably a response to the initial damage rather than a cause of the oedema.     

Prevalence of multiple sclerosis in a south London borough.

A survey of multiple sclerosis in the London Borough of Sutton, population 169,600, yielded 195 cases, giving an overall prevalence of 115/100,000. This is the third highest prevalence for a first survey of a geographical area in the United Kingdom, exceeded only by 127/100,000 in north east Scotland and 134/100,000 in Shetland. On the classification system of Allison and Millar, three quarters of the cases were classified as probable multiple sclerosis, 15% as early probable and latent multiple sclerosis, and 10% as possible multiple sclerosis. The mean age was 49 years, the mean age at onset was 34 years, and the mean duration of the disease was 15.4 years. The age standardised female to male ratio was 2:1. The prevalence found in this survey does not differ significantly from that recorded in the first north east Scotland survey. This study suggests that, firstly, the prevalence of multiple sclerosis in south east England is probably about 100/100,000 and, secondly, the latitudinal effect on the prevalence of multiple sclerosis in the United Kingdom is less appreciable than previously believed.     

工业化国家的环境问题—中、英生态学会联合学术讨论会论文

中英两国有着完全不同的历史。在英国,工业发展始于18世纪,随着财富的积累,迅速席卷了英伦三岛。由于对因此而造成的环境破坏没有得到重视,污染物不可避免地沉积下来,当时流行的一句话是“哪有烟尘,哪就有金钱”。尽管在某种程度上也曾提出过早期的     

There's a long, long trail a-winding: the complexities of GM foods regulation, a cautionary tale from the UK

The evolution of the regulatory process for genetically modified (GM) food in the United Kingdom is reviewed from its formal inception in 1988 to the present, drawing out lessons which have been learned from a series of cases brought to the committee for approval. The unexpected but highly professional anti-GM campaign is described, and issues regarding public perceptions of risk are discussed. Recent failures to find a consensus solution in the United Kingdom are described, and a proposal is made for a way forward.     

Effect of pulmonary oedema induced by α-naphthylthiourea on synthesis of cyclo-oxygenase products in rat isolated lungs

Synthesis of COP (prostaglandins; PG and thromboxanes; Tx) from exogenous and endogenous arachidonic acid (AA) was studied in isolated perfused lungs from rats treated in vivo with a single dose of α-naphthylthiourea (ANTU; 10mg/kg;). Lung dry: wet weight ratios showed changes characteristic of oedema between 6 and 16h after ANTU. Bioassay of COP showed that COP synthesis from exogenous AA was raised above control values in lungs from rats treated with ANTU, reaching a maximum at 16h after treatment. By radioimmunoassay, the major increase was in 6-oxo-PGF_1α, with lesser effects on PGE₂ and PGF_2α levels. Synthesis of bioassayable COP from endogenous AA induced by the calcium ionophore A23187 was increased as early as 2h after ANTU treatment and remained elevated up to 70h. In lungs 28h after ANTU, 6-oxo-PGF_1α release was greater than in normal lungs. These results show that in this model of pulmonary oedema, the potential for COP synthesis was increased. From the time course of this effect, increased COP synthesis was probably a response to the initial damage rather than a cause of the oedema.     

Evolutionary dynamics of local pandemic H1N1/2009 influenza virus lineages revealed by whole-genome analysis

Virus gene sequencing and phylogenetics can be used to study the epidemiological dynamics of rapidly evolving viruses. With complete genome data, it becomes possible to identify and trace individual transmission chains of viruses such as influenza virus during the course of an epidemic. Here we sequenced 153 pandemic influenza H1N1/09 virus genomes from United Kingdom isolates from the first (127 isolates) and second (26 isolates) waves of the 2009 pandemic and used their sequences, dates of isolation, and geographical locations to infer the genetic epidemiology of the epidemic in the United Kingdom. We demonstrate that the epidemic in the United Kingdom was composed of many cocirculating lineages, among which at least 13 were exclusively or predominantly United Kingdom clusters. The estimated divergence times of two of the clusters predate the detection of pandemic H1N1/09 virus in the United Kingdom, suggesting that the pandemic H1N1/09 virus was already circulating in the United Kingdom before the first clinical case. Crucially, three clusters contain isolates from the second wave of infections in the United Kingdom, two of which represent chains of transmission that appear to have persisted within the United Kingdom between the first and second waves. This demonstrates that whole-genome analysis can track in fine detail the behavior of individual influenza virus lineages during the course of a single epidemic or pandemic.     

Comparisons of therapeutic effects of levodopa,levodopa and selegiline,and bromocriptine in patients with early,mild Parkinson's disease: three year interim report. Parkinson's Disease Research Group in the United Kingdom.

OBJECTIVE--To determine the optimum treatment for early Parkinson''s disease. DESIGN--An open, long term, prospective randomised trial conducted by the Parkinson''s Disease Research Group of the United Kingdom. SETTING--93 hospitals throughout the United Kingdom. SUBJECTS--782 patients with early Parkinson''s disease who were not receiving dopaminergic treatment. INTERVENTIONS--Patients allocated to treatment with levodopa/dopa decarboxylase inhibitor alone (arm 1), levodopa/decarboxylase inhibitor/selegiline in combination (arm 2), or bromocriptine (arm 3). MAIN OUTCOME MEASURES--Disability assessment as judged by improvement on Hoehn and Yahr, modified Webster, and North Western University disability scales. Adverse event profile and mortality ratios. RESULTS--Interim results indicate that all three treatment regimens led to improvement in baseline disabilities after 12 months'' treatment and that deterioration in control was apparent by three years. No significant differences were found between the results of treatment in arm 1 and arm 2, but both were significantly more effective than bromocriptine (arm 3) and had fewer early adverse reactions. The adjusted difference (95% confidence interval) in Webster rating for arm 3 v 1 was 0.93 points (0.27 to 1.50; p = 0.0058) and for arm 3 v 2 was 1.25 points (0.61 to 1.89; p = 0.0002). The incidence of dyskinesias and motor oscillations, however, was significantly lower in arm 3 (2% and 5%, respectively) than in arm 1 (27% and 33%, respectively) and arm 2 (34% and 35%, respectively). CONCLUSIONS--As there were no marked differences in functional improvement between the three groups the choice of treatment in the early stages of Parkinson''s disease may not be critical.     

Phylogenetic surveillance of viral genetic diversity and the evolving molecular epidemiology of human immunodeficiency virus type 1

With ongoing generation of viral genetic diversity and increasing levels of migration, the global human immunodeficiency virus type 1 (HIV-1) epidemic is becoming increasingly heterogeneous. In this study, we investigate the epidemiological characteristics of 5,675 HIV-1 pol gene sequences sampled from distinct infections in the United Kingdom. These sequences were phylogenetically analyzed in conjunction with 976 complete-genome and 3,201 pol gene reference sequences sampled globally and representing the broad range of HIV-1 genetic diversity, allowing us to estimate the probable geographic origins of the various strains present in the United Kingdom. A statistical analysis of phylogenetic clustering in this data set identified several independent transmission chains within the United Kingdom involving recently introduced strains and indicated that strains more commonly associated with infections acquired heterosexually in East Africa are spreading among men who have sex with men. Coalescent approaches were also used and indicated that the transmission chains that we identify originated in the late 1980s to early 1990s. Similar changes in the epidemiological structuring of HIV epidemics are likely to be taking in place in other industrialized nations with large immigrant populations. The framework implemented here takes advantage of the vast amount of routinely generated HIV-1 sequence data and can provide epidemiological insights not readily obtainable through standard surveillance methods.     

Sequential changes in lung metabolism, permeability, and edema after ANTU

Lung injury and pulmonary edema were induced in rats after intraperitoneal injection of 10 mg/kg alpha-naphthylthiourea (ANTU). The time course of development of lung injury was assessed by the clearance of 99mTc-diethylenetriamine pentaacetate (99mTcDTPA) from the lung into the blood, the pharmacokinetics of tritiated prostaglandin E2 [( 3H]PGE2) in the isolated perfused lung, and by increase in the weight ratio (wet-to-dry) of lung. Two hours after ANTU administration, the clearance of 99mTcDTPA was significantly faster than in untreated animals and implied an increase in permeability of the alveolar-capillary barrier. This change preceded the increase in wet-to-dry weight ratio of lung, which was not significant until 5 h after ANTU administration. The pharmacokinetics of [3H]PGE2 were significantly altered after ANTU and these changes persisted beyond the time when both lung weight ratio and 99mTcDTPA clearance had recovered to normal values. We conclude that both 99mTcDTPA clearance and PGE2 pharmacokinetics change in ANTU-induced lung injury but with different time courses. In the progressive phase of lung injury due to ANTU, the early change in clearance of 99mTcDTPA suggests that an increased permeation of the alveolar capillary barrier by this small molecule precedes pulmonary edema due to an increased colloid permeability of the barrier. Abnormal metabolism in the pulmonary microvasculature persists when the permeability defect and edema have recovered.     

Granulocyte colony-stimulating factor enhances alpha-naphthylthiourea-induced pulmonary hypertension.

Physiopathological discrepancies exist between the most widely used models of pulmonary hypertension (PH), namely monocrotaline- and hypoxia-induced PH. The development of a new model could help in the understanding of underlying mechanisms. Repeated alpha-naphthylthiourea (ANTU) injections (5 mg/kg weekly, 3 wk) induced pulmonary vascular remodeling, which was associated with development of PH and right ventricular hypertrophy. ANTU followed by granulocyte colony-stimulating factor (G-CSF; 25 microgram. kg(-1). day(-1) subcutaneously, 3 days/wk) induced higher pulmonary arterial pressures and right ventricular hypertrophy than ANTU alone. Lidocaine, which inhibits neutrophil functions, inhibited PH exacerbation by G-CSF. Endothelial nitric oxide synthase expression, measured to assess ANTU-related endothelial toxicity, decreased significantly in ANTU-treated rats and fell even more sharply when G-CSF was given. This occurred despite a significant increase in vascular endothelial cell growth factor expression in lung and right ventricle in rats given ANTU alone and even more in rats given ANTU plus G-CSF. Repeated ANTU administration induces PH with vascular remodeling that can be further aggravated by the neutrophil activator G-CSF.     

National census of availability of neonatal intensive care. British Association for Perinatal Medicine

ObjectiveTo determine whether availability of neonatal intensive care cots is a problem in any or all parts of the United Kingdom.DesignThree month census from 1 April to 30 June 1999 comprising simple data sheets on transfers out of tertiary units.SettingThe 37 largest high risk perinatal centres in the United Kingdom.ParticipantsOne obstetric specialist and one neonatal specialist in each centre.ResultsAll units provided data. The number of intensive care cots in each unit was between five and 16. During the three months 309 transfers occurred (equivalent to 1236 per year), of which 264 were in utero and 45 postnatal. Sixty five in utero transfers involved multiple births, hence the census related to 382 babies (1528 per year). There was considerable regional variation. The reason for transfer in most cases was “lack of neonatal beds”.ConclusionsCurrently most major perinatal centres in the United Kingdom are regularly unable to meet in-house demand; this has implications for the service as a whole. The NHS has set no standards to help health authorities and primary care groups develop services relating to this specialty; such a step may well be an appropriate lever for change.     

STUDIES ON SEED HEALTH

An account is given of the survey made in 1940-55 to determine the incidence of the seed-borne fungal parasites of flax. It was shown that fibre flax seed produced in eastern and south-eastern England was relatively free from contamination with Colletotrichum linicola, Polyspora lini and Phoma sp. and that there was no build-up of infection in seed stocks in these areas. In the wetter and cooler regions west and north of the Pennines, conditions were more favourable for these fungi, and seed contamination tended to increase.
Seed contamination with Botrytis cinerea was general throughout the United Kingdom, with a tendency to be higher in coastal and upland areas. The incidence of Fusarium lini and Alternaria linicola in fibre flax seed produced in the United Kingdom was negligible.
The examination of seed samples from other countries indicated the possible importance of P. lini in Denmark, of B. cinerea and C. linicola in the Netherlands, of A. linicola as a contaminant of oil flax seed in Sweden, and of C. linicola in parts of Canada.
Seed disinfection, using a thiram product, proved useful for the control of flax diseases in general, but should be used as an ancillary to the method of avoiding seed infection by limiting the production of seed flax to areas where the risk of contamination is slight or absent. Where there is any risk of a build-up of contamination, seed disinfection should be carried out as a routine practice each season.     

The acquired immune deficiency syndrome and epidemic of infection with human immunodeficiency virus: costs of care and prevention in an inner London district.

The epidemic of the acquired immune deficiency syndrome (AIDS) and infection with human immunodeficiency virus (HIV) necessitates early planning of services and allocation of resources. The use of hospital resources by patients with AIDS and the planned additional costs of clinical and preventive services for the epidemic of infection with HIV were calculated for an inner London health district that has treated 18% of the cases in the United Kingdom. Patients with AIDS required on average 50 days of inpatient hospital care each at an estimated current average lifetime cost of pounds 6800. These costs, however, underestimated the additional capital and revenue costs of planned new preventive and treatment services, estimated as being pounds 388,000 revenue and pounds 472,000 capital for 1986-7. It is important to invest now in preventive services throughout the United Kingdom to reduce the future social and financial costs of AIDS.     

Distribution of Oriental and German cockroaches, Blatta orientalis and Blattella germanica (Dictyoptera), in the United Kingdom

Results are presented of a survey carried out by Rentokil Ltd on the distribution of the Oriental cockroach Blatta orientalis L. and the German cockroach Blattella germanica L. in the United Kingdom. The known ranges of both species are increased considerably by the findings of the survey, with several new vice-county records for Scotland (including the Western Isles), England and Wales. The frequency at which Blatta orientalis was observed in outdoor habitats may indicate that this species sometimes spreads to new areas without human assistance.