Renal effects of adenosine and their inhibition by theophylline in dogs

Summary The action of adenosine on renal blood flow and kidney function in dogs was studied with bolus injections and infusion of adenosine into the renal artery. Simultaneous infusions of theophylline, 1–5×10^–6 mol/min into the renal artery which did not affect renal function by itself inhibited the adenosine induced vasoconstriction. From the bolus injection studies a dose response curve (DRC) was constructed. Theophylline shifted the DRC to the right in a parallel manner. pA₂-pA₁₀ was 0.98 indicating that theophylline inhibition of the adenosine effects may be interpreted as a competitive antagonism. Infusions of adenosine (0.3–1.1 mol/min) caused a reduction of urine volume, sodium excretion and glomerular filtration rate (GFR). The decrease of GFR after adenosine infusion by 31.4% could be diminished by theophylline. It is suggested that adenosine action is based mainly on a constriction of the vasa afferentia in the outer zone of the cortex.with the technical assistance of O. JacobsPart of this work was presented on the 14. Frühjahrstagung der Deutschen Pharmakologischen Gesellschaft, Mainz, 18.–21. 3. 1973.Supported by Deutsche Forschungsgemeinschaft.     

Dietary zinc reduces uptake but not metallothionein binding and elimination of cadmium in the springtail,Orchesella cincta

In metal-polluted environments, high concentrations of metals such as zinc, cadmium, copper, and lead are present. Many studies have been conducted to determine uptake and binding of the nonessential, toxic metal cadmium. Effects of essential metals on this uptake and binding remain unclear. The aim of the present study was to determine the effect of zinc on cadmium kinetics and metallothionein induction in the springtail Orchesella cincta. Exposure experiments were conducted with cadmium only, zinc only, and cadmium + zinc. Metallothionein was isolated to determine zinc binding to or induction of this cadmium-binding protein. In animals exposed to cadmium only and to cadmium + zinc, metallothionein was induced. In animals exposed to zinc only, no metallothionein was induced, and zinc did not bind to the metallothionein induced by cadmium. Cadmium uptake rate was significantly lower in animals exposed to cadmium + zinc than in animals exposed to cadmium only. No significant pattern of uptake and elimination of zinc was observed. Zinc concentrations in the animals were not significantly different for the different exposures, demonstrating that this element is regulated by O. cincta. These results suggest a protective role of zinc in the uptake of cadmium but no interference of zinc with the internal cadmium distribution and elimination.     

Three-Dimensional Soft Tissue Prediction Using Finite Elements

Abstract Background and Aim: The prediction of soft tissue esthetics is important for achieving an optimal esthetic outcome in orthodontic treatment planning. Applicable procedures have so far been restricted to two-dimensional profile predictions that have not proven to be very reliable. The goal of this investigation was therefore to develop a novel finite element-based procedure that allows a three-dimensional, easily visualized, quantitative analysis and prediction of soft tissue behavior for the clinician. The procedure to be developed should be easy to handle and not entail any additional radiation exposure for the patient. Material and Methods: Using a three-dimensional scanner, the facial surfaces of 20 probands were digitalized and individual FEM models were generated. Results: After reduction of data redundancy via several conversion steps, a patient-specific simulation model was prepared consisting of 20,000 to 40,000 individual elements to which specific physical properties could be assigned. The average time required for generating a virtual model was 50 minutes. Problems occurring during model generation were rare (mainly shadowing phenomena and movement artifacts). Conclusion: The procedure outlined herein makes the reliable generation of patient-specific simulation models possible for facial soft tissue prediction in orthodontics.     

Fasting and 2-hour plasma glucose and insulin: relationship with risk factors for cardiovascular disease in overweight nondiabetic children

OBJECTIVE

To determine whether elevated fasting or 2-h plasma glucose and/or insulin better reflects the presence of cardiovascular disease (CVD) risk markers in an overweight pediatric population with normal glucose tolerance.

RESEARCH DESIGN AND METHODS

A total of 151 overweight youths (8–17 years old) were evaluated with oral glucose tolerance tests and measurement of CVD risk factors. The study population was categorized according to quartiles of fasting and 2-h glucose and insulin levels. ANCOVA, adjusted for age, sex, race, Tanner stage, and percent body fat (measured by dual-energy X-ray absorptiometry), was used to compare metabolic variables between the quartiles of glucose and insulin groups.

RESULTS

Increasing quartiles of fasting and 2-h insulin were associated with increasing CVD risk factors. Glucose quartiles on the other hand, either fasting or at 2 h, were not.

CONCLUSIONS

These data suggest that hyperinsulinemia may be the earliest and/or primary metabolic alteration in childhood associated with risk markers for CVD. Prospective studies are needed.The prevalence of childhood overweight is increasing relentlessly (1–2). An increase in the rates of pre-diabetes and type 2 diabetes seems to follow the upward trend of obesity (3). Longitudinal studies in adults demonstrate that cardiovascular disease (CVD) changes are established before a diagnosis of diabetes is made and correlate better with 2-h glucose levels (4–5). Guidelines on diabetes and CVD from the European Society of Cardiology and the European Association for the Study of Diabetes have summarized that 2-h glucose provides better information about risk for CVD than fasting glucose and predicts increased cardiovascular risk in subjects with normal fasting glucose levels (6).Meta-analyses of prospective data from 11 populations have shown that hyperinsulinemia, defined by the highest quartile cutoff for fasting insulin, was associated with cardiovascular mortality independently of other risk factors (7). A review of 19 Western prospective studies showed that the odds ratio (OR) for coronary heart disease for raised fasting insulin as well as nonfasting insulin were more modest than previously suspected (OR 1.12 [95% CI 0.98–1.28] and 1.35 [1.14–1.60], respectively) (8).No studies have evaluated whether a fasting or 2-h glucose and/or insulin value reflects better the presence of CVD risk factors in overweight children with normal glucose tolerance. The purpose of this investigation was to assess the relationship between glucose and insulin quartiles and CVD risk factors in an overweight pediatric population.     

In vitro and in vivo targeting properties of iodine-123- or iodine-131-labeled monoclonal antibody 14C5 in a non-small cell lung cancer and colon carcinoma model.

PURPOSE: The monoclonal antibody (mAb) 14C5 is a murine IgG1 directed against a yet undefined molecule involved in cell substrate adhesion found on the surface of malignant breast cancer tissue. mAb 14C5 is able to inhibit cell substrate adhesion and invasion of breast cancer cells in vitro. In normal tissues as well as in the stroma surrounding in situ carcinomas of the breast, no expression of the antigen 14C5 occurs. The aim of this study was to investigate the in vitro and in vivo targeting properties of 123I- and 131I-labeled mAb 14C5 as a novel agent for radioimmunodetection and radioimmunotherapy. EXPERIMENTAL DESIGN: Internalization of mAb 14C5 was investigated with 125I-labeled mAb 14C5 and by confocal laser scanning microscopy. Biodistribution studies of 131I-labeled mAb 14C5 and planar gamma imaging were done in nude mice bearing an A549 (non-small cell lung carcinoma) or a LoVo (colon carcinoma) tumor. RESULTS: Internalization studies with both A549 and LoVo cells showed that 125I-labeled mAb 14C5 is slowly internalized with approximately 30% of the initially bound mAb 14C5 internalized after 2 hours at 37 degrees C. Internalization of mAb 14C5 could be visualized with confocal laser scanning microscopy. In vivo, radioisotope uptake peaked at 24 hours for both tumor models (n = 5) with no significant difference in percentage of injected dose/g tissue (A549 10.4 +/- 0.8 and LoVo 9.3 +/- 0.8). Via planar gamma camera imaging, A549 lung tumors as well as LoVo colon tumors could be clearly visualized. CONCLUSIONS: The in vitro and in vivo targeting properties of 123I- and 131I-labeled mAb 14C5 are promising and could provide a new antibody-based agent for radioimmunodetection and radioimmunotherapy of patients bearing antigen 14C5-expressing tumors.     

Downstream health impacts of employment losses during the COVID-19 pandemic

Objectives The Canadian workforce has experienced significant employment losses during the COVID-19 pandemic, in part as a result of non-pharmaceutical interventions to slow COVID-19 transmission. Health consequences are likely to result from these job losses, but without historical precedent for the current economic shutdown they are challenging to plan for. Our study aimed to use population risk models to quantify potential downstream health impacts of the COVID-19 pandemic and inform public health planning to minimize future health burden.MethodsThe impact of COVID-19 job losses on future premature mortality and high-resource health care utilization (HRU) was estimated using an economic model of Canadian COVID-19 lockdowns and validated population risk models. Five-year excess premature mortality and HRU were estimated by age and sex to describe employment-related health consequences of COVID-19 lockdowns in the Canadian population.ResultsWith federal income supplementation like the Canadian Emergency Response Benefit, we estimate that each month of economic lockdown will result in 5.6 new high-resource health care system users (HRUs), and 4.1 excess premature deaths, per 100,000, over the next 5 years. These effects were concentrated in ages 45–64, and among males 18–34. Without income supplementation, the health consequences were approximately twice as great in terms of both HRUs and premature deaths.ConclusionEmployment losses associated with COVID-19 countermeasures may have downstream implications for health. Public health responses should consider financially vulnerable populations at high risk of downstream health outcomes.Supplementary InformationThe online version contains supplementary material available at 10.17269/s41997-021-00588-3.     

广东省消灭淋巴丝虫病的监测与审评

目的：消灭传染源，阻断传播，达到全省消灭淋巴丝虫病。方法：按消灭丝虫病的监测方案进行病原学和媒介学监测。结果：至2001年，全省血检1575905人，发现和治疗微丝蚴血症4074例。原丝虫病流行区各流行县(市)于无微丝蚴血症次年起，按达到基本消灭丝虫病标准后10年内和10年后分别统计，共病原学监测178个乡镇316544人和341个乡镇520120人；每县(市)均在3个以上的病原学监测点进行蚊媒监测，在429个点共解剖雌性致倦库蚊250377只和中华按蚊(含嗜人按蚊)2297只。人群和蚊媒均未发现人体丝虫感染，结果显示这些地区丝虫病的传播已被阻断。结论：2001年9月，全省按照卫生部消灭丝虫病审评方案的要求，通过省级审评达到卫生部消灭淋巴丝虫病的标准。     

Autoantibodies against oxidatively modified low-density lipoprotein in patients with Beh?et's disease.

BACKGROUND: Change of lipids and lipoprotein metabolism and an imbalance of the oxidant-antioxidant system related to the disease activity have been reported in Beh?et's disease. Therefore, there is a tendency of oxidative modification of lipids and lipoproteins in patients with the disease. OBJECTIVE: To investigate serum autoantibodies against oxidatively modified low-density lipoprotein (oxLDL) as a marker for the degree of in vivo oxidation of lipoproteins in Beh?et's disease. METHODS: Serum autoantibodies against oxLDL, total cholesterol, triacylglycerol, HDL cholesterol, LDL cholesterol, apolipoprotein (Apo) AI, Apo B, alpha1-antitrypsin, alpha2-macroglobulin and erythrocyte sedimentation rate were determined in 37 patients and 30 sex- and age-matched healthy volunteers. Autoantibodies against oxLDL were measured by a commercial enzyme-linked immunosorbent assay. RESULTS: Serum autoantibody levels against oxLDL were significantly higher in patients than in controls (425 +/- 365 and 187 +/- 132 mU/ml, respectively; p < 0.05). The levels of autoantibodies against oxLDL in the patients were found to correlate with total cholesterol, LDL cholesterol, HDL cholesterol and alpha1-antitrypsin levels (r = 0.38, p < 0.05; r = 0.42, p < 0.05; r = -0.38, p < 0.05; r = 0.42, p < 0. 05, respectively). CONCLUSION: It has been shown in previous studies that high autoantibody titers against oxLDL may be important in diseases with atherosclerosis as seen in systemic lupus erythematosus and rheumatoid arthritis. High autoantibody titers against oxLDL are not specific for Beh?et's disease but probably important for pathologic processes in the disease. We suggest that increased levels of autoantibodies against oxLDL may be a factor responsible for endothelial dysfunction and development of vascular pathology in Beh?et's disease.     

Displaced scapular fractures: indication and long-term results of open reduction and internal fixation

Displaced scapular fractures are often found in polytraumatized patients. In emergency treatment they assume a minor role. Advances in dealing with severely injured patients in most instances allow us to perform an operation on the fractured scapula within the first 2 weeks after injury. A differentiated approach is necessary as exclusively conservative treatment does not always bring about good results. From 1981–1991 we performed open reduction and internal fixation (ORIF) in 25 patients with displaced fractures of the scapula. The long-term results could be assessed in 20 patients after an average of 6.1 years. The different types of fractures were classified according to Habermeyer/Ideberg, and the Constant score was used in the evaluation of results. Some 64% of patients were involved in road accidents, and 64% suffered concomitant injuries. Articular fractures (n = 6) were the most common ones, followed by fractures of the coracoid process (n = 5) and the neck of the scapula (n = 2). There was no early postoperative complication, and follow-up showed a breakage of K-wires in one patient (fracture of the acromion). Thirteen patients obtained a very good, two patients a good, four a fair and one a poor result (according to the Constant score). Fractures of the scapular neck had the best results in terms of pain, daily activity, range of motion, and strength) as compared with fractures of the glenoid and apophyseal fractures. The radiological evaluation of the articular fractures showed advanced arthrosis of the glenoid with a discrepancy of the surface of more than 2 mm in one patient and a moderate arthrosis (first degree) with an intra-articular displacement of less than 2 mm in another one. The remaining four patients were free of articular incongruencies and other signs of arthrosis. In this retrospective study of operativley treated patients with displaced scapular fractures, more than 70% achieved very good or good results. In severely injured patients, the diagnosis of scapular fractures should be carefully excluded. Timely detection by radiography and computed tomography is mandatory for judicious decision-making concerning conservative and operative treatment.     

Effects of a nonpeptide motilin receptor antagonist on proximal gastric motor function

AIM: To assess the effects of the motilin receptor antagonist RWJ-68023 on basal and motilin-stimulated proximal gastric volume. METHODS: Eighteen healthy male volunteers received RWJ-68023 in two different doses or placebo for 135 min. After 45 min, subjects received a motilin infusion for 90 min. Proximal gastric volume was measured with a barostat at constant pressure and during isobaric distensions. Abdominal symptoms were scored using visual analogue scales. Motilin and RWJ-68023 concentrations were assessed by radioimmunoassay and liquid chromatography-mass spectrometry, respectively. RESULTS: Both dosages of RWJ-68023 were safe and well tolerated. The most common adverse events were of gastrointestinal origin. RWJ-68023 did not affect basal proximal gastric volume, but the high-dose RWJ-68023 reduced the contractile effect of motilin on the stomach. This antagonizing effect of RWJ-68023 was only significant (P = 0.014) during the distension procedure. CONCLUSIONS: The RWJ-68023 doses used in this study were selected to accomplish plasma concentrations that would block the motilin effect entirely. However, the antagonizing effect of RWJ-68023 was partial and only present when the tonic condition of the stomach was modulated by motilin.