Ethanol and Acetaldehyde After Intraperitoneal Administration to Aldh2-Knockout Mice-Reflection in Blood and Brain Levels

This paper reports, for the first time, on the analysis of ethanol (EtOH) and acetaldehyde (AcH) concentrations in the blood and brains of Aldh2-knockout (Aldh2-KO) and C57B6/6J (WT) mice. Animals were administrated EtOH (1.0, 2.0 or 4.0 g/kg) or 4-methylpyrazole (4-MP, 82 mg/kg) plus AcH (50, 100 or 200 mg/kg) intraperitoneally. During the blood tests, samples from the orbital sinus of the eye were collected. During the brain tests, dialysates were collected every 5 min (equal to a 15 µl sample) from the striatum using in vivo brain microdialysis. Samples were collected at 5, 10, 15, 20, 25, 30 and 60 min intervals post-EtOH and -AcH injection, and then analyzed by head-space GC. In the EtOH groups, high AcH levels were found in the blood and brains of Aldh2-KO mice, while only small traces of AcH were seen in the blood and brains of WT mice. No significant differences in EtOH levels were observed between the WT and the Aldh2-KO mice for either the EtOH dose. EtOH concentrations in the brain were comparable to the EtOH concentrations in the blood, but the AcH concentrations in the brain were four to five times lower compared to the AcH concentrations in the blood. In the AcH groups, high AcH levels were found in both WT and Aldh2-KO mice. Levels reached a sharp peak at 5 min and then quickly declined for 60 min. Brain AcH concentrations were almost equal to the concentrations found in the blood, where the AcH concentrations were approximately two times higher in the Aldh2-KO mice than in the WT mice, both in the blood and the brain. Our results suggest that systemic EtOH and AcH administration can cause a greater increase in AcH accumulation in the blood and brains of Aldh2-KO mice, where EtOH concentrations in the Aldh2-KO mice were comparable to the EtOH concentrations in the WT mice. Furthermore, detection of EtOH and AcH in the blood and brain was found to be dose-dependent in both genotypes.     

Half-Lives of Sulphadoxine and Trimethoprim After a Single Intravenous Infusion in Cows

DAVITIYANANDA, DANIS and FOLKE RASMUSSEN: Half-lives of sulphadoxine and trimethoprim after a single intravenous infusion in cows. Acta vet. scand. 1974, 15, 356–365. — The half-life of sulphadoxine in plasma (11 hrs.) is much longer than that of trimethoprim (50–103 min.) and in accordance to this traces of sulphadoxine are demonstrated in the milk 3 days after the infusion, while trimethoprim could not be detected in milk 2 days after the infusion. The apparent volume of distribution is 0.37 for sulphadoxine and 1.14 for trimethoprim, i.e. 37 % and 114 % of the body weight, respectively. sulphadoxine; trimethoprim; half-life; cow.     

Effect of Rapid Intravenous Infusion on Serum Concentrations of Amphotericin B

The magnitude of the concentrations of amphotericin B produced in serum of patients with systemic mycoses may significantly influence the outcome of therapy with this drug. Since amphotericin B is conventionally administered in intravenous infusions lasting 4 to 6 hr, we asked whether faster infusions of this drug might yield higher serum concentrations without an increase in dose. This question was studied in three patients who received 16 infusions of this drug: eight infusions administered slowly (5 hr) and eight administered rapidly (45 min). Serum concentrations after each rapid infusion were compared with those after a slow infusion administered to the same patient. The mean serum concentration of amphotericin B 1 hr after the rapid infusions (2.02 mug/ml) was significantly higher (P < 0.001) than the mean serum concentration of amphotericin B 1 hr after the slow infusions of this drug (1.18 mug/ml). Mean serum concentrations 18 and 42 hr after rapid infusion remained slightly but not significantly higher than respective mean concentrations after slow infusions. By yielding higher initial serum concentration, rapid intravenous infusion may be therapeutically more effective than slow infusion of amphotericin B. Although rapid infusions caused no more toxicity than did slow infusions, the lack of greater toxicity with rapid infusion of amphotericin B should be further documented prior to extensive clinical application of this procedure.     

Correlations of Trace Element Levels in the Diet,Blood, Urine,and Feces in the Chinese Male

In order to explore the associations between trace elements in dietary intake and the other three biological media (blood, urine, or feces) and inter-element interactions among the latter, we simultaneously collected 72-h diet duplicates, whole blood, and 72-h urine and feces from 120 free-living healthy males in China. Correlations among the toxic (cadmium [Cd], lead [Pb]), and nutritionally essential (zinc [Zn], copper [Cu], iron [Fe], manganese [Mn], selenium [Se], iodine [I]) elements were evaluated using Spearman rank correlation analysis based on analytical data determined by inductively coupled plasma-mass spectrometry. Dietary Cd intakes were highly correlated with the fecal Cd and blood Cd levels. Inverse correlations were found for Fe–Cd and Fe–Pb in both diet versus blood and diet versus feces. Cd–Zn and Cd–Se were significantly directly correlated in the urine and feces. Cd–Se and Pb–Se were negatively correlated in blood. In addition, there existed an extremely significant association between urinary Se and urinary I. Moreover, the other two highly direct correlations were found for Se–Fe and for I–Fe in urine. Improved knowledge regarding their mutual associations is considered to be of fundamental importance to understand more the complex interrelationships in trace element metabolism.     

Simple Method for Rapid Determination of Antibiotic Blood Levels

A simple method for the rapid determination of antibiotic blood levels is described. Results are readily obtainable within 4 to 6 hr. The reported procedure is based upon determination of the highest dilution of a patient's serum capable of inhibiting dextrose fermentation by a standardized inoculum of a staphylococcus strain or of an Escherichia coli strain, when colymycin or polymyxin are involved, as compared to previously determined endpoints in this regard of defined concentrations of the different antibiotics dissolved in normal human serum. Excellent correlation was observed with 36 serum specimens that contained different antimicrobial agents in varied concentrations when simultaneously assayed by the standard method and the subject procedure of this report.     

In-Use Contamination of Intravenous Infusion Fluid

During the 1970 to 1971 nationwide epidemic of septicemias caused by Enterobacter cloacae and Enterobacter agglomerans traced to intrinsic contamination of Abbott intravenous infusion products, 94 infusion systems manufactured by Baxter Laboratories were studied microbiologically and epidemiologically during hospital use. Intravenous fluid from 10 systems (11%) contained microorganisms, usually Staphylococcus or Bacillus species; one infusion was heavily contaminated with Klebsiella pneumoniae. No national epidemic organisms, E. cloacae or E. agglomerans (formerly Erwinia), were recovered, suggesting that during this period frequent contamination with these organisms was unique to Abbott's infusion products. Contamination in this study appeared to be extrinsic in origin (introduced during clinical use) and related to the duration of continuous intravenous therapy. Nine of 61 systems (15%) that had been used longer than 48 h were contaminated, whereas only 1 of 33 used less than 48 h (3%) contained microorganisms. This study and the recent national outbreak indicate that contamination of infusion fluid, both from intrinsic and extrinsic sources, must be recognized as an additional risk of intravenous therapy; however, a once-daily replacement of the delivery apparatus can significantly diminish this hazard.     

Lead and Mercury Levels in Preterm Infants Before and After Blood Transfusions

Biological Trace Element Research - Very low birth weight (VLBW) infants usually receive packed red blood cell unit (pRBC) transfusions. Heavy metal transfer via pRBCs is not widely discussed...     

Duration of Voluntary Breath Holding and Blood Parameters

Stange's and Genci's functional tests performed at rest and during exercise and blood tests have shown that the duration of voluntary breath holding depends on appearance in the blood of hypoxia, hypercapnia, and acidosis signs only after the influence of fatigue of respiratory muscles and respiratory center has become insufficient.     

Rapid Initiation of Intravenous Epoprostenol Infusion Is the Favored Option in Patients with Advanced Pulmonary Arterial Hypertension

Background

Intravenous infusion (IVI) of epoprostenol is an effective treatment for patients with advanced pulmonary arterial hypertension (PAH). However, there is no widely accepted standard method for initiating the IVI therapy. This study evaluated the hemodynamic improvements achieved with IVI epoprostenol to determine the optimal protocol for treatment initiation.

Methods and Results

We retrospectively analyzed 42 consecutive PAH patients who underwent IVI epoprostenol in Keio University Hospital from 2001 to 2013. The study group comprised 30 women with a mean age of 34.3 ± 1.9 years. The etiology of PAH was idiopathic or heritable PAH (I/HPAH) in 38 cases, PAH associated with connective tissue disease in 3, and Eissenmenger’s syndrome in the remaining case. We divided the patients into rapid- and slow-initiation therapy groups according to the cumulative epoprostenol dose administered during the first 180 days, and compared the hemodynamic changes between the groups. The median cumulative doses were 6142 ± 165 μg/kg and 3998 ± 132 μg/kg epoprostenol, respectively. While there were no significant differences in mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), or cardiac index (CI) between the groups before the IVI epoprostenol therapy, the rapid-initiation therapy group achieved significant improvements in these hemodynamic data compared with the slow-initiation therapy group (P < 0.005) at the follow-up right-heart catheterization (RHC).

Conclusion

Rapid initiation of IVI epoprostenol therapy achieved the optimal hemodynamic improvements in patients with severe PAH.     

Effect of Zinc Supplementation on the Status of Thyroid Hormones and Na,K, and Ca Levels in Blood Following Ethanol Feeding

The influence of zinc (Zn) on the serum levels of triiodothyronine (T₃), thyroxine (T₄), thyroid-stimulating hormone (TSH) and sodium (Na), potassium (K), and calcium (Ca) was evaluated following ethanol toxicity to the rats. To achieve this, male Wistar rats (150–195 g) were given 3 ml of 30% ethanol orally, and zinc was given in the form of zinc sulfate (227 mg/l) in their drinking water daily for 8 weeks. Ethanol feeding resulted in a slight decrease in T₃ and T₄ levels and a significant increase in thyroid-stimulating hormone concentration, which may be due to the direct stimulatory effect of ethanol on thyroid. Interestingly, when zinc was given to these rats, all the above levels were brought quite close to their normal levels, thus indicating the positive role of zinc in thyroid hormone metabolism. Serum Zn and Ca levels were found to be reduced, but Na levels were raised upon ethanol feeding. Restoration of normal levels of these metals upon zinc supplementation to ethanol fed rats confirms that zinc has potential in alleviating some of the altered thyroid functions following ethanol administration.     

Effects of Intravenous Infusion of Phosphorothioate Oligonucleotides on Coagulation,Complement Activation and Hemodynamics

Abstract

Several acute toxicities in monkeys have been associated with administration of phosphorothioate oligonucleotides including effects on coagulation and complement cascades. These effects are transient in nature and the severity is closely associated with peak plasma concentrations of the oligonucleotide. Similar properties have been observed for several oligonucleotides with different base sequences.     

不同时间脂肪乳输注对大鼠葡萄糖输注率的影响

目的观察不同时间脂肪乳输注使血浆游离脂肪酸（FFA）升高对大鼠葡萄糖输注率（GIR）的影响。方法分别给大鼠输注脂肪乳2、5、7和48 h,行高胰岛素-正血糖钳夹试验评价葡萄糖输注率,测定血浆葡萄糖、FFA。结果与生理盐水输注组比较,2 h脂肪乳输注使血浆FFA升高了2倍（P〈0.01）,GIR下降27%（P〈0.05）,脂肪乳输注5 h GIR降低了52%（P〈0.01）,7 h GIR降低56%（P〈0.01）,输注48 h脂肪乳GIR降低58%（P〈0.01）,5 h组7、h组及48 h脂肪乳输注组间GIR差异没有统计学意义。结论大鼠输注脂肪乳使FFA浓度达到基础值的3倍左右,可复制出脂毒性胰岛素抵抗的模型,而且胰岛素抵抗达到一定程度后保持恒定。     

The Almost-one Parameter Hypothesis Applied to Pharmacokinetics of Ethanol Infusion

They say that the pharmacokinetics of constant-rate intravenous infusion of ethanol obeys the Henri-Michaelis-Menten (H-M-M) model. In analysing the original data from the viewpoint of the almost-one parameter hypothesis (see box 1), we found that the whole process should be divided into four phases and the H-M-M model was valid only in the last phase.     

Behaviour of Standard Gravity-fed Administration Sets Used for Intravenous Infusion

The major factor influencing drip rate during intravenous infusion using a standard administration set is the variation in the venous pressure of the patient. Creep in the plastic material, though present, is shown to be unimportant. For steady and accurate infusion it is necessary to provide the ordinary gravity-fed administration set with some form of servo-control mechanism.     

Chromium, Cadmium, and Lead Levels in Urine of Children with Autism and Typically Developing Controls

Although potentially harmful effects of heavy metals are well known, limited numbers of studies exist regarding their relationship with autism. The aim of this study was to investigate urine levels of some heavy metals such as of chromium (Cr), cadmium (Cd), and lead (Pb) in children with autism and healthy subjects. Urine levels of Cr, Cd, and Pb were measured by atomic absorption spectrometry in 30 children with autism and compared with 20 healthy controls. Urine Cd and Pb levels were found as significantly decreased in children with autism compared to healthy subjects (p?<?0.05). On the other hand, urine Cr levels were significantly higher in children with autism than healthy subjects (p?<?0.05). This study suggested that autism may be associated with significant decrease in excretion rate of Cd and Pb and a significant increase excretion rate in the levels of Cr in the urine. These results have indicated that further studies are warranted for investigation of possible roles of heavy metals in autism.     

Rapid Detection of Certain Basic Drugs in Urine

Equipment costing only a few pounds can be used to detect a wide range of drugs in urine by anyone with a minimum of scientific knowledge. A run of tests takes about half an hour to perform and cost about 10p.