Renal acid excretion in early infancy

In early infancy, complex disorders of acid base metabolism are more frequent than in any other age group, with a predisposition to metabolic acidosis due to an age-related low renal capacity for acid excretion and an unphysiologically high actual renal acid load in nutrition with common formulas. Recently in preterm and small-for-gestational-age infants, persistent maximum renal net acid excretion (NAE) with subnormal or normal blood acid base status, impaired weight gain, and adaptive hormonal reactions have been observed. Incipient late metabolic acidosis is one example of a mixed disorder of acid base metabolism with maximum renal NAE in early infancy. Alkali therapy is highly effective and can be realized both on an individual basis, using urine pH screening as a diagnostic criterium for maximum renal acid stimulation, or on a general preventive level using modified standard formula with a reduced actual renal NAE similar to that seen on alimentation with human milk. From an integrated point of view, the low glomerular filtration rate and renal capacity for acid excretion beyond the developmental age of more than 44 weeks, may well be interpreted as the result of a specific adaptation to breast feeding sparing energy, and thus an evolutionary advantage for the survival of mother and child. Received July 10, 1996; received in revised form and accepted October 7, 1996     

Controlled Release of Substituted Benzole and Naphthoic Acids Using Carbopol ® Gels: Measurement of Drug Concentration Profiles and Correlation to Release Rate Kinetics

Purpose. The objective of this study is to correlate drug release mechanism with measured drug concentration profiles in gel layers of Carbopol^® matrices containing mesalamine or benzoic acid. Methods. Release rate experiments with Carbopol^® matrices were performed using a rotating disk apparatus. Matrices were frozen and the gel layer in the matrices was sliced using a microtome in a cryostat. Drug concentration profiles were determined by direct measurement of the concentration of the drug in the gel slices. The pH of the slices was measured using microelectrodes, and water content was measured by Karl Fisher titration. Results. The concentration gradient in mesalamine matrices decreased over time and correlated with square root of time release rate kinetics. The concentration profiles of benzoic acid were unchanged over time and correlated with zero order release rate kinetics. Carbopol gel layers were highly hydrated (93–95% water). Gel layers in matrices with mesalamine had a more alkaline microenvironmental pH. This higher pH resulted in increased growth of the thickness of the gel layer and a reduction drug diffusivity in comparison to benzoic acid matrices. Conclusions. The release rate kinetics of mesalamine and benzoic acid correlated to the measured concentration profiles. The shape of the concentration profiles is determined by the rate of growth of the Carbopol^® gel layer and drug diffusivity.     

The effects of cysteamine on the upper gastrointestinal tract of children with cystinosis

The purpose of this study was to evaluate the effects of cysteamine on gastric acid output and serum gastrin levels in children with nephropathic cystinosis. We studied four children with nephropathic cystinosis receiving a dose of free base cysteamine of 14.35 mg/kg four times a day (range 12.30 – 18.80 mg/kg). Gastric acid was measured for the hour before and after administration of the medication. Serum gastrin levels were obtained at 0, 30, 60, and 90 min following the medication. Gastrointestinal anatomy was evaluated by endoscopy and biopsy. Following administration of the medication, all subjects showed an increase in gastric acid output. Mean acid output increased from 0.79 to 2.22 mEq/h. Mean gastric acid output adjusted for body weight increased from 0.03 to 0.09 mEq/kg per hour. Following administration of the medication, all subjects showed an increase in serum gastrin. The mean increase above the base value was 38.3 pg/dl. Two of the four subjects demonstrated visual and histological evidence of inflammation. Cysteamine has a marked effect on gastric acid production and serum gastrin, even at the dose used in children with nephropathic cystinosis. The clinical effect of this acid production is unknown but may be significant. Received February 13, 1996; received in revised form February 25, 1997; accepted February 27, 1997     

顺丁烯二酸水溶液的热反应动力学

研究了不同温度、浓度条件下，顺丁烯二酸（顺酸）非催化反应网络，即顺酸可生成反丁烯二酸（反酸）和苹果酸，反酸与苹果酸存在可逆反应。建立了该反应网络的动力学模型。测定了不同反应条件下顺酸、反酸和苹果酸浓度随时间变化的规律，据此，动力学参数进行了估值。     

全反式维甲酸对骨髓纤维细胞的影响

通过纤维细胞集落(CFU-F)的培养,观察了急性早幼粒细胞性白血病(APL)的CFU-F,结果APL 患者较正常骨髓明显低下(4.3±1.63/2×10~5细胞)(n=9);完全缓解后则上升达正常水平(12.4±2.55/2×10~5)。体外试验,维甲酸(RA)加入CFU-F 培养系后,CFU-F 下降为3.11±1.24/2×10~5细胞,明显低于对照组8.5±1.57/2×10~5(P<0.05)。提示RA 对骨髓纤维细胞有抑制作用,此结果可能为RA 治疗骨髓纤维化提供初步依据。     

Effect of linoleic acid, linoleic acid anilide, and arachidonic acid on the expression of adhesion molecules on human neutrophils

The effects of linoleic acid, linoleic acid anilide, and arachidonic acid on the expression of CD11b/CD18, CD11c/CD18 integrins and l-selectin on human neutrophils were studied by flow cytometry in a whole blood assay. None of these compounds had any effect on the basal expression of CD11b, CD11c, or l-selectin in the concentration range of 20–100 μM. However, linoleic acid at a concentration of 1000 μM slightly up-regulated CD11b and CD11c by a factor of 2.1 and 1.7, respectively. Linoleic acid, linoleic acid anilide, and arachidonic acid did not affect the formyl-methionyl-leucyl-phenylalanine induced up-regulation of CD11b or CD11c. However, linoleic acid and linoleic acid anilide slightly inhibited the phorbol myristate acetate (PMA)-induced expression of CD11b, which was decreased by 27 and 21% at concentrations of 100 and 1000 μM, respectively. Likewise, arachidonic acid at 40 μM inhibited the PMA-induced expression of CD11b by 19%. Our results suggest that linoleic acid, linoleic acid anilide, and arachidonic acid do not dramatically affect the expression of leukocyte adhesion molecules in a whole blood assay. Received: 17 February 1997  / Accepted: 5 May 1997     

缺氧缺血性脑病新生鼠胃壁内一氧化氮的改变

目的探讨缺氧缺血性脑病新生鼠胃壁局部一氧化氮（ＮＯ）的改变及窒息对消化系统的影响。方法采用二氢硫辛酰胺脱氢酶ＮＡＤＰＨ组织化学方法，检测２４只正常或缺氧新生鼠胃壁各层一氧化氮合成酶（ＮＯＳ）的分布变化。结果急性缺氧组与正常对照组相比，ＮＯＳ阳性产物无论在分布、染色深浅、纤维密度及ＮＯＳ阳性胞体数目上，差异均无显著意义（Ｐ＞０．０５）。但在缺氧缺血性脑病组，其肌层的ＮＯＳ阳性纤维无论是密度还是染色深浅，均明显强于正常对照组，ＮＯＳ阳性胞体亦明显多于正常对照组，其差异有非常显著意义（Ｐ＜０．０１）；而粘膜和粘膜下层的ＮＯＳ分布与正常对照组相比，差异无显著意义（Ｐ＞０．０５）。结论窒息时胃动力降低及胃粘膜病变与一氧化氮在胃壁内的改变有关     

Folic acid in the treatment of acute watery diarrhoea in children: a double-blind, randomized, controlled trial

One-hundred and six male children aged 6-23 months with a history of acute watery diarrhoea of less than 72 h duration were randomized to receive either folic acid in a dose of 5 mg at 8-h intervals or placebo for 5 d. There were 54 children in the folic acid group and 52 in the placebo group. The admission characteristics were comparable between the two groups. No significant differences were observed in the intake of oral rehydration solution or stool output between the groups. The mean ± SD of total stool output (g kg⁻¹) was 532 ± 476 vs 479 ± 354 and the duration (h) of diarrhoea was 108 ± 68 vs 103 ± 53 in the folic acid vs placebo group, respectively. The findings, therefore, should have a positive influence on preventing the inappropriate use of folic acid in acute diarrhoea.     

Analysis of the Inhibitory Effect of Oestradiol on Functional GABA/5-HT Relationship in the Rat Suprachiasmatic Area

The purpose of this study was to test the capacity of oestradiol to modulate the stimulating effect of a-aminobutyric acid (GABA) on serotonin (5-HT) metabolism, previously described in the Suprachiasmatic area of the male rat. After an in vivo stimulation of GABA transmission by systemic administration of a GABA-transaminase inhibitor (amino-oxyacetic acid) or a GABA_B agonist (RS-baclofen), the 5-HT metabolism was studied in the Suprachiasmatic area of ovariectomized, and ovariectomized oestradiol-treated rats. Amino-oxyacetic acid or RS-baclofen treatment increased the endogenous content of 5-HT in the Suprachiasmatic area of males and ovariectomized rats. These two treatments were without effect in ovariectomized oestradiol-treated rats. GABA transmission stimulation induced by amino-oxyacetic acid treatment failed to affect the release and synthesis of 5-HT in ovariectomized oestradiol-treated rats while it increased these two parameters of 5-HT metabolism in the Suprachiasmatic area of male and ovariectomized rats. To investigate the main target of oestradiol effect, comparative studies of the serotoninergic and GABAergic metabolism in the Suprachiasmatic area were performed in the three experimental groups. Under our experimental conditions the endogenous 5-HT metabolism was similar between ovariectomized and ovariectomized oestradiol-treated rats. Nevertheless, 5-HT metabolism was higher in the two female groups than in the male group. Neither GABA metabolism nor GABAergic response to GABA-related drug treatment differed between ovariectomized, and ovariectomized oestradiol-treated rats. However, the turnover of GABA was higher when compared to the two female groups. It is concluded that the lack of 5-HT responsiveness to GABA transmission stimulation in ovariectomized oestradiol-treated rats was not related to an effect of oestradiol on 5-HT metabolism or to an effect of the steroid on GABA turnover. Furthermore, our results suggest a sex difference in the activity of serotoninergic and GABAergic systems in the Suprachiasmatic area.