Regional extraction of circulating norepinephrine, DOPA, and dihydroxyphenylglycol in humans

Dihydroxyphenylglycol (DHPG) is the main intraneuronal metabolite of the sympathetic neurotransmitter, norepinephrine (NE), and dihydroxyphenylalanine (DOPA) the immediate product of the rate-limiting step in catecholamine biosynthesis. Simultaneous measurements of regional rates of appearance (spillovers) of NE, DOPA, and DHPG in plasma have the potential to provide unique information about aspects of sympathoneural function but have not actually been measured in humans. In the present study, spillovers of DHPG, DOPA, and NE in the heart, head, leg, and lungs, were estimated from regional extraction fractions of infused [3H]-1-NE, DHPG, and [13C6]DOPA or unlabelled DOPA in humans during cardiac catheterization. There was little cardiac extraction of DHPG (7 +/- SEM 2%) or DOPA (8 +/- 4%) but substantial extraction of NE (69 +/- 4%). Values for cardiac spillover of DHPG and DOPA therefore were similar to values for the arteriovenous increment times plasma flow (arteriovenous production rate), whereas the cardiac spillover of NE averaged about 7-times the NE arteriovenous production rate. Cardiac DHPG spillover (28 +/- 3 ng/min) exceeded the spillovers of NE (9 +/- 2 ng/min) and DOPA (15 +/- 4 ng/min). In contrast, cranial DOPA spillover (159 ng/min) exceeded those of NE and DHPG by 8- and 2-fold and accounted for about 1/10 of the total spillover of DOPA into arterial plasma. In the femoral vascular bed, arteriovenous production rates of NE and DHPG were unrelated to femoral spillovers of NE and DHPG. Arterial and regional clearances of [13C6]DOPA were similar to those of unlabelled DOPA. The results suggest that (1) endogenous NE, DOPA, and DHPG all are released into the bloodstream by the heart, head, and limbs of humans; (2) DHPG and DOPA are not co-released with NE; (3) cardiac arteriovenous production rates of DOPA and DHPG can be used to indicate cardiac spillover of these catechols, whereas the cardiac NE arteriovenous production rate substantially underestimates cardiac NE spillover; and (4) estimates of limb spillover of NE and DHPG require concurrent measurements of the corresponding regional clearances.     

Rapid hypertensinogenic effect of lead: studies in the spontaneously hypertensive rat.

Chronic lead exposure may cause hypertension in normotensive rats. This hypertensinogenic effect has been attributed to perturbations in the renin-angiotensin axis, the contractile response of the vascular smooth muscle, or the intracellular Ca2+ homeostasis as a consequence of the inhibition of Na(+)-K(+)-ATPase activity. In this study we examined the short-term effect of lead exposure on blood pressure, plasma renin activity, vascular contractility, and renal Na(+)-K(+)-ATPase activity and abundance in the spontaneously hypertensive rat. Our data indicate that modest lead exposure caused blood pressure elevation within two weeks in this rat strain that is genetically susceptible to the development of hypertension. This rapid blood pressure-elevating effect did not appear to depend on the mechanisms described in hypertension associated with more chronic lead exposure listed above. This acute model provides an additional approach to the study of lead-induced hypertension.     

High-efficiency stable gene transfection using chloroquine-treated Chinese hamster ovary cells

We describe a highly efficient stable gene transfection procedure for Chinese hamster ovary (CHO) cells using a modification of the calcium phosphate-DNA coprecipitation method. We have found that treatment of CHO cells with chloroquine increases the efficiency of gene transfer by up to 20-fold (from approx. 0.01% to approx. 0.2%) when transfection is done using the pSV2-neo plasmid. The optimized transfection procedure requires that CHO cells to be incubated with calcium phosphate-DNA coprecipitate and chloroquine (100 µM) for a total of 16 h. By using high-molecular-weight human genomic DNA as a DNA source for transfection, we show that this procedure is equally efficient for stably transferring a much larger gene, such as the 49-kb human hypoxanthine phosphoribosyltransferase gene.     

Fusiform posterior cerebral artery aneurysm treated with excision and end-to-end anastomosis. Case report

A case of a ruptured fusiform aneurysm of the posterior cerebral artery is reported. The aneurysm was excised and end-to-end anastomosis was carried out between the two ends of the posterior cerebral artery. There is no previous report of a posterior cerebral artery aneurysm treated with this technique. The pertinent literature is reviewed and the significance of this technique in the treatment of unclippable cerebral aneurysms is discussed.     

Species- and sex-specific variations in binding of ochratoxin A by renal proteins in vitro

The mycotoxin ochratoxin A (OTA) is a potent renal carcinogen in rodents and induces renal fibrosis in pigs. Furthermore, OTA has been associated with the development of renal tumors and nephropathies in humans. Large species- and sex-differences are observed in sensitivity toward OTA-mediated toxicity and carcinogenicity, yet neither the mechanism(s) resulting in OTA toxicity nor the reasons for the observed species- and sex-specificities are known. This paper investigated variations in OTA handling viz binding to renal proteins which could possibly explain the observed differences in OTA susceptibility in vivo and in vitro. The results obtained via a modification of a standard receptor-binding assay demonstrated the presence of at least one homogeneous binding component in renal cortical homogenates from pig, mouse, rat and humans. This component was shown to bind OTA in a specific and saturable manner. A range of compounds selected for their affinity for steroid receptors and/or for various known organic anion transporters were employed in a competition assay to answer the question whether this homogenous OTA binding component represents a steroid-like receptor component or one of the known organic anion transporters of the kidney. Although many of the compounds were able to compete with OTA for protein-binding, the competition patterns displayed a distinct species specificity and did not correspond to the competition patterns associated with presently known organic anion transporters of the kidney in the mouse, rat or human. The data thus suggests the presence of a new organic anion transporter or more likely, a cytosolic binding component of unknown function with high affinity and capacity for OTA binding in humans, rats, mice and possibly pigs.     

臀、会阴及其周围Ⅲ度烧伤的早期切痂治疗体会

目的　总结臀、会阴及其周围Ⅲ度烧伤的早期切痂治疗的经验。方法　对 3 2例臀、会阴Ⅲ度烧伤患者于伤后 3～ 7d内行切痂 ,嵌皮、大张皮片或皮瓣修复创面的资料进行回顾分析。结果　本组病例皮瓣、皮片大部分成活好 ,外观、功能恢复满意。结论　臀、会阴及周围Ⅲ度烧伤早期切痂治疗可缩短疗程 ,减少外观及功能障碍 ,近远期效果好     

The significance of a rapid cold hemagglutination test for detecting mycoplasma infections in children with asthma exacerbation.

BACKGROUND AND PURPOSE: Mycoplasma pneumoniae infection is a frequent cause of community-acquired respiratory infections in children and adults. However, standardized, rapid, specific methods for its diagnosis are lacking. The relationship between M. pneumoniae infection and asthma exacerbation has been recently discussed in the literature. We investigated the accuracy of rapid detection of mycoplasma infection by cold hemagglutination test compared to conventional enzyme immunoassays. The clinical characteristics of mycoplasma infection seen during emergent visits in asthmatic children were reviewed. METHODS: We retrospectively reviewed medical records of patients with asthma exacerbation visiting the Department of Pediatric Emergency, National Taiwan University Hospital, over a 12-month period. Subjects 2-18 years of age diagnosed with asthma at our outpatient clinic were included in this study. Patients with immunodeficiency, congenital anomalies, neurological diseases and irregular follow-up were excluded. RESULTS: A total of 269 children (174 males and 95 females) with a mean (+/- standard deviation) age of 6.15 +/- 3.08 years were included. The prevalence of asthma exacerbation in regular follow-up patients was 13.4%, and as many as 19.6% of cases (74/378 person-times) required hospitalization. Asthma attacks were most prevalent during December. 126 patients had both rapid cold hemagglutination testing and mycoplasma immunoglobulin M titers determined using acute blood samples drawn in the emergency room; 46 (36.5%) of these patients demonstrated mycoplasma infection. Sensitivity and specificity of the rapid cold hemagglutination test was 78.3% and 41.3%, respectively. The positive predictive value was 43.4%. Comparison of patients with or without mycoplasma infection revealed no differences in gender, age, chest X-ray findings, and most symptoms/signs and laboratory data, except that more signs of fever and auscultatory rales were seen in the non-mycoplasma infection group. CONCLUSIONS: Mycoplasma infections could be an exacerbating factor for asthma, and the rapid cold hemagglutination test should not be a guideline for prescribing macrolides in the emergency room.