A comprehensive review of intake estimates of di-isononyl phthalate (DINP) based on indirect exposure models and urinary biomonitoring data

Di-isononyl phthalate (DINP) is a high molecular weight general purpose plasticizer used principally in the manufacture of flexible polyvinyl chloride (PVC) articles. DINP metabolites can be measured in biological media such as blood and urine. However, measurement of a substance in the blood or urine does not by itself mean that the chemical causes or is associated with adverse health outcomes. This is particularly pertinent given the advances in modern analytical techniques whereby ever diminishing trace amounts of substances can be detected. Therefore, it is a scientific necessity that risk assessors understand the relationship of biomonitoring data to estimation of exposure so that appropriate comparisons can be made to the no observed adverse effects levels (NOAELs) or other points of departure from toxicological studies in animals. In this paper, estimates of daily DINP intake are calculated for various population segments based on urinary biomonitoring data and are compared to estimates of exposure based on indirect methods and to health-based exposure guidance values. In general, intake estimates converge on a mean of 1–2 μg/kg/day regardless of source of exposure or population cluster; a value 2-orders of magnitude lower than health-based exposure guidance values, ranging from 120 to 290 μg/kg/day, which have been established by regulatory authorities and other authoritative bodies as representing acceptable levels.     

Life span differences in digoxin uptake and excretion

Little is known about the underlying mechanisms for the altered susceptibility to digitalis with age. To this end, we investigated the digoxin uptake and excretion in mice and rats of different ages through the life span, including the periods of growth, maturity, and aging. Digoxin uptake by cardiac slices was linear from 0 to 15 min, with steady state occuring at 45 min. The rate in the mature 12-month mouse was significantly less than that of the senescent 30-month mouse. The kinetic parameters revealed a significant decrease in Km with a concomitant increase in Vmax during senescense. On the other hand uptake by renal cortical slices was highest during growth, decreased to a maturation plateau and then declined further during senescence. Renal clearance and the secretory capacity for digoxin increased 30 and 62%, respectively, during growth and progressively decreased from maturity through senescence and were 59 and 77%, respectively, during aging. In summary, there was an increase in digoxin clearance and tubular activity during growth, and in increase in myocardial uptake of digoxin and a decrease in renal excretion during aging. Thus, these results may explain the clinical observations of altered susceptibility to digitalis with age.     

The biliary excretion and pharmacokinetics of mezlocillin in jaundiced patients with external bile drainage

ABSTRACT— The biliary excretion and pharmacokinetics of mezlocillin have been studied in jaundiced patients with total external bile drainage through a percutaneous transhepatic catheter. In 10 of 11 studies, 2 g mezlocillin intravenously resulted in biliary concentrations sufficient to exceed the minimum inhibitory concentrations of most common biliary pathogenic organisms. In 6 h, 0.2–6.2% of the dose given was recovered in bile. The biliary clearance was 0.21–7.82 ml/min and increased with the duration of biliary decompression. The serum half-life of mezlocillin was prolonged (1.81 ± 0.23 h, mean ± SD), and was due to reduced biliary and renal clearance.     

Angiotensinogen gene T235 variant: a marker for the development of persistent microalbuminuria in children and adolescents with type 1 diabetes mellitus

AIM: We examined genetic polymorphisms in the renin-angiotensin system (RAS) coding for angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) for angiotensinogen (AGT) M235T and angiotensin II receptor type 1 (AGTR1) A1166C as predictors for the development of microalbuminuria (MA) in children with type 1 diabetes mellitus (T1DM). METHODS: Four hundred fifty-three (215 males, 238 females) T1DM children [median (interquartile range): age, 16.7 years (13.9-18.3); diabetes duration, 6.9 years (3.3-10.8); age at diagnosis, 9.1 years (5.8-11.8)] were followed prospectively from diagnosis until the development of MA (two of three consecutive overnight urine samples with albumin excretion rates of > or =20 and <200 microg/min). Kaplan-Meier survival curves and Cox proportional multivariate model estimated the probability of developing MA and the relative risk for MA among different variables. RESULTS: MA developed in 41 (9.1%) subjects. The frequencies of genotypes were as follows: ACE-II 112 (25%), ACE-ID 221 (49%), and ACE-DD 117 (26%) (n=450); AGT-MM 144 (32%), AGT-MT 231 (51%), and AGT-TT 77 (17%) (n=452); AGTR1-AA 211 (47%), AGTR1-AC 204 (45%), and AGTR1-CC 37 (8%) (n=452). The cumulative risk for the development of MA was higher in ACE-DD versus ACE-ID/II groups (log-rank test, P=.05), and a trend was noticed when AGT-TT was compared to AGT-MT/MM groups (log-rank test, P=.08). AGT-TT polymorphism conferred a fourfold increased risk for MA compared to AGT-MM/MT (hazard ratio=3.8; 95% confidence interval=1.43-10.3; P=.008). INTERPRETATION: Our findings suggest that RAS gene polymorphism at AGT M235T is a strong predictor for early MA in young T1DM subjects.     

长江下游丘陵地区环境碘来源调查

目的 调查长江下游丘陵地区环境碘来源.方法 对0～岁、6～岁、12～岁及成人、妊娠、哺乳妇女在同一时点同时测定其每天食盐食用量、食盐碘含量和尿碘排泄量.结果 0～岁、6～岁、12～岁及成人、妊娠、哺乳妇女环境碘来源分别为79.4μg/d,123.5μg/d,283.5μg/d和151.0μg/d,其平均水平为117.0μg/d.结论 环境碘来源是调整食盐加碘量的基础.     

胰岛素强化治疗对早期糖尿病肾病的疗效观察

目的观察胰岛素强化治疗对2型糖尿病合并早期糖尿病肾病(DN)的临床疗效。方法选取我院糖尿病早期肾病患者116例,A组给予胰岛素强化治疗,B组应用口服降糖药治疗。结果胰岛素强化治疗组治疗后尿白蛋白排泄率(UAER)、空腹血糖、餐后两小时血糖、糖化血红蛋白(GHbA1c)显著下降,空腹C肽及餐后2小时C肽显著升高,与治疗前及对照组比较均有统计学意义(P<0.05),其中逆转为正常蛋白尿14例;对照组上述指标治疗前、后比较无统计学意义(P>0.05),进展为临床期糖尿病6例。结论应用胰岛素强化治疗控制血糖水平,可能会改善糖尿病预后,延缓糖尿病肾病进展。     

血液透析联合血液灌流治疗甲氨蝶呤排泄延迟的护理

总结应用血液透析联合血液灌流救治6例行大剂量甲氨蝶呤化疗后药物排泄延迟的急性淋巴细胞白血病病人的护理措施。血液净化护理重点为大剂量甲氨蝶呤化疗不良反应的观察与护理、股静脉导管维护、血液透析联合血液灌流治疗常见并发症的观察与护理等。本组6例病人未出现血液净化护理并发症,5例症状好转出院,1例因合并严重的肺部和肠道感染放弃治疗后院外死亡。     

Occurrence of a mosquito vector in bird houses: Developmental consequences and potential epidemiological implications

Even with continuous vector control, dengue is still a growing threat to public health in Southeast Asia. Main causes comprise difficulties in identifying productive breeding sites and inappropriate targeted chemical interventions. In this region, rural families keep live birds in backyards and dengue mosquitoes have been reported in containers in the cages. To focus on this particular breeding site, we examined the capacity of bird fecal matter (BFM) from the spotted dove, to support Aedes albopictus larval growth. The impact of BFM larval uptake on some adult fitness traits influencing vectorial capacity was also investigated. In serial bioassays involving a high and low larval density (HD and LD), BFM and larval standard food (LSF) affected differently larval development. At HD, development was longer in the BFM environment. There were no appreciable mortality differences between the two treatments, which resulted in similar pupation and adult emergence successes. BFM treatment produced a better gender balance. There were comparable levels of blood uptake and egg production in BFM and LSF females at LD; that was not the case for the HD one, which resulted in bigger adults. BFM and LSF females displayed equivalent lifespans; in males, this parameter was shorter in those derived from the BFM/LD treatment. Taken together these results suggest that bird defecations successfully support the development of Ae. albopictus. Due to their cryptic aspects, containers used to supply water to encaged birds may not have been targeted by chemical interventions.     

The effects of Sarconesiopsis magellanica larvae (Diptera: Calliphoridae) excretions and secretions on fibroblasts

Sarconesiopsis magellanica is a necrophagous blowfly which is relevant in both forensic and medical sciences. Previous studies regarding this species have led to understanding life-cycle, population and reproduction parameters, as well as identifying and characterising proteolytic enzymes derived from larval excretions and secretions (ES). As other studies have shown that ES proteolytic activity plays a significant role in wound healing and fibroblasts play a relevant role in granulation tissue formation during such healing, the present study was aimed at analysing the biological effect of S. magellanica larval ES on fibroblasts. ES were obtained from third-instar larvae and added to fibroblast cells at three concentrations (10, 5 and 1 μg/mL) to evaluate their behaviour. MTT assays were used for analysing cell proliferation and viability, whilst cell adhesion was measured by optical density with 10% SDS. Fibroblast migration and morphology was recorded by microscopic observation. ES did not affect fibroblast viability and induced an increase in cell proliferation; cell adhesion became reduced, whilst cell migration through extracellular matrix increased. ES also induced a decreased cell surface and morphological alterations. Changes in all the above-mentioned parameters were reduced when ES were incubated at 60 °C, probably due to protease denaturation. These results suggested that the proteases contained in S. magellanica larval ES contributed towards granulation tissue formation, increased cell migration and promoted cell proliferation. All these data support carrying out further experiments aimed at validating S. magellanica usefulness in larval therapy.