Inhibitory Effect of Estrogens,Phytoestrogens,and Caloric Restriction on Oxidative Stress and Hepato-toxicity in Aged Rats

Objective To investigate the protective effect of 17β-estradiol （E2）, peganum harmala extract （PHE） administration and calorie restriction （CR） treatment （60%） on oxidative stress and hepato-toxicity in aged rats. Methods Eighteen months old animals that were treated at the age of 12 months were divided into 4 groups： normal control group with free access to food, E2 treatment group, PHE treatment group and CR treatment group of the food given to control group. Six male rats at the age of 4 months were used as a reference group. Results Aging significantly decreased superoxide dismutase （SOD）, catalase （CAT） and glutathione peroxidase （GPX）, and increased lactate deshydrogenase （LDH）, gamma-glyiamyl transferase （GGT）, pbosphatase alkalines （PAL）, aspartate and lactate transaminase （AST and ALT） activities in the liver. Aging also induced an increased lipid peroxidation level, histological changes and a decreased E2 level. However, treatment with E2, PHE, and CR increased 17β-estradiol, and decreased hepatic dysfunction parameters and lipid peroxidation as well as histological changes in the liver of aged rats. Conclusion The antioxidant and hepatoprotective activity of PHE and CR is possibly attributed to its ability to increase E2 level, which as an antioxidant, acts as a scavenger of ROS. Further studies on the pharmaceutical functions of E2 in males may contribute to its clinical application.     

2型糖尿病降糖治疗对癌症风险的影响

2型糖尿病患者实性肿瘤的发生风险可能受降糖治疗的影响。为了了解肿瘤的发生风险与口服降糖药物、人胰岛素、胰岛素类似物治疗的关系,研究者对62809例患者进行了一项回顾性队列研究。所有患者年龄〉40岁,并且在2000年后开始应用胰岛素或口服药物治疗。患者被分成4个治疗组：单独应用二甲双胍、单独应用磺脲类、上述两种药物联用、应用胰岛素。应用胰岛素治疗的患者又被分为4个亚组：甘精胰岛素、长效人胰岛素、双相胰岛素类似物、双相人胰岛素。     

Target setting in intensive insulin management is associated with metabolic control: the Hvidoere Childhood Diabetes Study Group Centre Differences Study 2005

Swift PGF, Skinner TC, de Beaufort CE, Cameron FJ, Åman J, Aanstoot H‐J, Castaño L, Chiarelli F, Daneman D, Danne T, Dorchy H, Hoey H, Kaprio EA, Kaufman F, Kocova M, Mortensen HB, Njølstad PR, Phillip M, Robertson KJ, Schoenle EJ, Urakami T, Vanelli M, Ackermann RW, Skovlund SE for the Hvidoere Study Group on Childhood Diabetes. Target setting in intensive insulin management is associated with metabolic control: the Hvidoere Childhood Diabetes Study Group Centre Differences Study 2005. Objective: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control. Methods: Clinical data and questionnaires were completed by adolescents, parents/carers and diabetes teams in 21 international centres. HbA1c was measured centrally. Results: A total of 2062 adolescents completed questionnaires (age 14.4 ± 2.3 yr; diabetes duration 6.1 ± 3.5 yr). Mean HbA 1c = 8.2 ± 1.4% with significant differences between centres (F = 12.3; p < 0.001) range from 7.4 to 9.1%. There was a significant correlation between parent (r = 0.20) and adolescent (r = 0.21) reports of their perceived ideal HbA1c and their actual HbA1c result (p < 0.001), and a stronger association between parents' (r = 0.39) and adolescents' (r = 0.4) reports of the HbA1c they would be happy with and their actual HbA1c result. There were significant differences between centres on parent and adolescent reports of ideal and happy with HbA1c (8.1 < F > 17.4;p < 0.001). A lower target HbA1c and greater consistency between members of teams within centres were associated with lower centre HbA1c (F = 16.0; df = 15; p < 0.001). Conclusions: Clear and consistent setting of glycaemic targets by diabetes teams is strongly associated with HbA1c outcome in adolescents. Target setting appears to play a significant role in explaining the differences in metabolic outcomes between centres.     

Genome scanning of Amazonian Plasmodium falciparum shows subtelomeric instability and clindamycin-resistant parasites

Here, we fully characterize the genomes of 14 Plasmodium falciparum patient isolates taken recently from the Iquitos region using genome scanning, a microarray-based technique that delineates the majority of single-base changes, indels, and copy number variants distinguishing the coding regions of two clones. We show that the parasite population in the Peruvian Amazon bears a limited number of genotypes and low recombination frequencies. Despite the essentially clonal nature of some isolates, we see high frequencies of mutations in subtelomeric highly variable genes and internal var genes, indicating mutations arising during self-mating or mitotic replication. The data also reveal that one or two meioses separate different isolates, showing that P. falciparum clones isolated from different individuals in defined geographical regions could be useful in linkage analyses or quantitative trait locus studies. Through pairwise comparisons of different isolates we discovered point mutations in the apicoplast genome that are close to known mutations that confer clindamycin resistance in other species, but which were hitherto unknown in malaria parasites. Subsequent drug sensitivity testing revealed over 100-fold increase of clindamycin EC₅₀ in strains harboring one of these mutations. This evidence of clindamycin-resistant parasites in the Amazon suggests that a shift should be made in health policy away from quinine + clindamycin therapy for malaria in pregnant women and infants, and that the development of new lincosamide antibiotics for malaria should be reconsidered.The World Health Organization (WHO) campaign to eradicate malaria in the 1950s and 1960s was initially largely successful in decreasing the burden of malaria. Drug failure eventually led to a resurgence in the number of malaria cases in the 1990s and caused vast numbers of deaths that could have been avoided through a better appreciation of the prevalence of drug-resistant malaria and more informed choices of first-line drugs (Greenwood et al. 2008). While malaria deaths are now likely to decline, primarily because of the introduction of artemisinin-based combination therapy (ACT) as well as increased insecticide spraying and the use of bed nets (Greenwood et al. 2008), this may only be temporary. Indeed, there has been a general increase in the parasite clearance times in ACT-treated Plasmodium falciparum malaria cases from near the Thai–Cambodian border, suggesting that case numbers may soon begin increasing (Dondorp et al. 2009).Remarkably, although artemisinin is used on tens of millions of individuals annually, we have little idea about how it acts or which genes contribute to resistance, confounding the community''s ability to monitor the spread of resistance using molecular markers and to deploy new therapies (Eastman and Fidock 2009). The fact that the genes involved in artemisinin resistance are not known is due to a variety of problems, including the fact that in vivo resistance has not been replicated in vitro (Dondorp et al. 2009). Additionally, the association of phenotypes with genotypes in P. falciparum is hampered by the difficulties in performing complementation studies due to extremely low transfection efficiencies and the fact that laboratory crosses of drug-sensitive and drug-resistant P. falciparum cannot be easily performed. Thus, it took more than 40 yr between the identification of chloroquine resistance in the field (Harinasuta et al. 1965) and confirmation that resistance is due to mutations in the chloroquine resistance transporter (pfcrt, MAL7P1.27) (Wellems et al. 1990; Fidock et al. 2000; Sidhu et al. 2002). While the recombinant progeny from one of the three extant crosses (Walliker et al. 1987; Wellems et al. 1990; Hayton et al. 2008) have most famously been used to map chloroquine resistance (Wellems et al. 1990), they have been used to map loci contributing to a wide variety of phenotypes that distinguish parental clones. For example, they have already been scored for a variety of different phenotypes that are related to drug sensitivity, including antifolate sensitivity (Wang et al. 2004b), quinine sensitivity (Ferdig et al. 2004), expression levels (Gonzales et al. 2008), and plasmodial surface ion channels (Alkhalil et al. 2009), but they could be scored for any phenotype that quantitatively distinguishes the parental strains Dd2 and HB3, such as propensity to mutate in the laboratory (Rathod et al. 1997). However, there are a limited number of phenotypes that distinguish these two laboratory strains that were derived from patients 40 yr ago. While more crosses would provide valuable data for many researchers interested in parasite genetics, there are ethical considerations associated with using primates in research. An alternative to creating new recombinant progeny is to find existing recombinant isolates that arose from recent meioses occurring in humans. Such parasites might be identified by performing full-genome analyses on parasites from a limited geographical area and could provide the malaria community with an unprecedented number of parasites differing in a variety of phenotypes for use in linkage or quantitative trait locus (QTL) studies.One attractive group of parasites for full genome investigation is from the Peruvian Amazon. Due to the low transmission rates it is expected that parasites isolated from an individual will be from a single clone infection. In addition, malaria was eradicated in the 1960s in this region but re-emerged with epidemics in the early 1990s (Aramburu Guarda et al. 1999; Branch et al. 2005), suggesting that the genomes might contain signatures of selective sweeps (Wootton et al. 2002; Roper et al. 2004). At first, malaria in this region was treated with chloroquine (first-line), sulfadoxine-pyrimethamine (second-line), and quinine with clindamycin or tetracycline (third-line) (Aramburu Guarda et al. 1999), but the emergence of resistance resulted in widespread chloroquine and antifolate treatment failure (Durand et al. 2007). Today, malaria remains hypoendemic with low levels of seasonal transmission of P. falciparum and P. vivax parasites in the region surrounding Iquitos, Peru (Roshanravan et al. 2003). Previous studies of parasites in the region describe only one or two independent haplotypes for important drug-resistance genes, suggesting a limited number of founders for this population (Bacon et al. 2009) and suggest that we might find recombinant progeny in this region.In this study, we performed genome scanning on 14 P. falciparum patient isolates from a limited geographical region. We show that the parasite population in the Peruvian Amazon is very closely related, with combinations of only two to four different genotypes for drug resistance genes, suggesting at most four parental haplotypes. Furthermore, some parasites taken from different patients who presented with symptoms were essentially clones of one another, while others were recent meiotic siblings that could be useful in linkage studies or eQTL analyses. Unexpectedly, genome scanning also revealed uncharacterized mutations in the apicoplast 23S rRNA that distinguished some Peruvian strains from the reference strain, 3D7. Because one of these mutations had been previously associated with lincosamide antibiotic resistance in the chloroplast and many bacterial species (Vester and Douthwaite 2001), sensitivity testing was performed revealing that the parasites harboring the mutation had indeed become resistant to clindamycin, a drug used in combination with quinine to treat pregnant women and infants for malaria in Peru. These are the first documented cases of resistance to this class of drugs in malaria and suggest that the use of lincosamide drugs in treating malaria should be reconsidered.     

Effect of hair removal by Nd:YAG laser on the recurrence of pilonidal sinus

Background  Pilonidal sinus (PNS) is chronic inflammatory process of the skin in the natal cleft. Management of PNS is mainly surgical. Although different types of surgery have been performed, the recurrence rate is still high.
Objective  To evaluate the effectiveness of laser hair removal (LHR) in the natal cleft area on the recurrence rate of PNS as an adjuvant therapy after surgical treatment.
Methods  Twenty five patients with PNS were included in this study. Fifteen patients underwent LHR treatment using Nd:YAG laser after surgical excision of PNS (Patients group) while ten subjects with PNS did not do LHR and served as a control group.
Results  All of the patients were male patients. Their age ranged from 17 to 29 years with a mean of 21.60 ± 3.13 years. They had Fitzpatrick skin type III, IV and V. The patients have got 3 to 8 sessions of LHR (mean 4.87 ± 1.64). Follow up period lasted between 12 to 23 months. None of the patients, who underwent LHR, has required further surgical treatment to date. Seven patients out of ten in the control group have developed recurrent PNS. Pain was the most frequent side effect and it was seen in 6 patients (40%).
Conclusion  LHR can prevent the recurrence of PNS. LHR should be advised as an essential adjuvant treatment after surgical excision of PNS. In non-complicated recurrent PNS, LHR is strongly advocated to be started before and continued after doing surgical treatment.     

Reduction in mortality from sudden infant death syndrome in New Zealand: 1986-92

Mortality from sudden infant death syndrome (SIDS, or cot death) in New Zealand has been high by international standards (4/1000 live births). Within New Zealand the rate is higher in Maori than in non-Maori (predominantly European infants) and higher in South Island than in North Island. The National Cot Death Prevention Programme aims to reduce the prevalence of four modifiable risk factors for SIDS, namely infants sleeping prone, maternal smoking, lack of breast feeding, and infants sharing a bed with another person. The aim of this study is to describe the total postneonatal and total SIDS mortality in New Zealand from 1986 to 1992. Official publications from 1986 to 1990 and preliminary death notifications for 1991 and 1992 were examined. Deaths from all causes in the postneonatal age group (28 days to 1 year) and the total number of deaths from SIDS irrespective of age decreased markedly in 1990 and has continued to decrease. This decrease occurred particularly in non-Maori groups, in South Island, and in the winter months. The proportion of infants sleeping in a prone position has decreased from 43% to less than 5%. This suggests that the prone position is causally related to SIDS. The mechanism appears to be related directly or indirectly to environmental temperature.     

Travel and changes in routine do not increase the risk of sudden infant death syndrome

We investigated the relationship between travel and changes in routine and the sudden infant death syndrome (SIDS) among 485 SIDS cases compared with 1800 randomly selected control infants. There was no increased risk of SIDS with travel. Special events, such as christenings, were not associated with an increased risk of SIDS. However, visits to and by friends or relatives were associated with a significantly reduced risk of SIDS after controlling for potential confounders (odds ratios = 0.70; 95% confidence interval = 0.52, 0.96). These findings may indicate less social support in SIDS cases.     

Arterial oxygen tension and response to oxygen breathing in differential diagnosis of congenital heart disease in infancy

Arterial oxygen tension was measured from radial artery samples in 276 infants referred for cardiological investigation. Values obtained during air breathing in infants with congenital heart disease showed considerable overlap between 'cyanotic' and 'acyanotic' groups, and are of limited diagnostic use. By contrast, values obtained while breathing oxygen in concentrations of over 80%, measured in 182 infants, allowed clear differentiation between these groups. All infants with acyanotic, but only 2 of 109 with cyanotic lesions, achieved an arterial oxygen tension of more than 150 mmHg. In the cyanotic group the response to oxygen breathing was significantly greater in common mixing situations and in the hypoplastic left heart syndrome than with either pulmonary outflow tract obstruction or transposition of the great arteries. Infants with transposition had a significantly lower mean arterial oxygen tension in air than infants with other forms of cyanotic congenital heart disease. Of 23 infants whose final diagnosis was primary lung disease but in whom cyanotic congenital heart disease had been suspected, 7 achieved arterial oxygen tensions of more than 150 mmHg during oxygen breathing, and on this basis cardiac catheterization was not performed. We therefore conclude that measurement of the arterial oxygen tension while breathing high concentrations of oxygen should be routinely performed in the initial assessment of sick infants with suspected congenital heart disease.