Nephrotoxicity of cyclosporin A in humans: effects on glomerular filtration and tubular reabsorption rates

The contention that cyclosporin A (CyA) nephrotoxicity may be due to renal afferent arteriolar constriction was inferred from rat studies showing CyA to increase renal vascular resistance, to reduce glomerular filtration rate (GFR) and delivery of tubular fluid from the end of the proximal tubule to the loop of Henle (Vprox), and to increase proximal fractional reabsorption. In order to test whether the mechanism of human CyA nephrotoxicity is similar to its rat analogue, and whether CyA treatment causes prolonged renal malfunction after drug withdrawal, renal function was investigated with clearance techniques including lithium clearance (CLi) as a measure of Vprox. The subjects were patients (n = 11) with previously normal renal function, given CyA in the treatment of ocular manifestation of extrarenal disease, or bone-marrow transplant recipients. Nine out of these eleven patients were investigated before and during CyA treatment: GFR (P less than 0.05) and Vprox (P less than 0.005) decreased while proximal fractional reabsorption increased (P less than 0.01). In six patients investigated before CyA was given, and re-examined a mean of 273 days (range 84-384 days) after CyA withdrawal, CLi was reduced (P less than 0.05) while mean GFR was not significantly lowered (0.5 greater than P greater than 0.2). In one of these six patients GFR was reduced to a subnormal value of 26 ml min-1 (1.73 m2 body surface)-1. In conclusion, human and rat CyA nephrotoxicity have the same pattern of renal functional deterioration. Cyclosporin A nephrotoxicity was evident in patients investigated a mean of 9 months after CyA withdrawal.     

Antagonist capacities of nifedipine, captopril, phenoxybenzamine, prostacyclin and indomethacin on cyclosporin A induced impairment of rat renal function

Experimental evidence indicates that cyclosporin A (CyA) nephrotoxicity is due to renal arteriolar constriction, reducing renal blood flow, glomerular filtration rate (GFR), and delivery of tubular fluid from the end of the proximal tubule to the loop of Henle. The proximal tubular fractional reabsorption (PFR) is increased. Therefore, the impact on renal function of vasodilating agents was studied in rats given CyA. Conscious catheterized rats and clearance techniques were used. In acute experiments a preexisting CyA-nephrotoxicity was resistant to infusion of phenoxybenzamine, prostacyclin, captopril, nifedipine and indomethacin. Concomitant treatment with captopril and CyA did not improve renal function, while concomitant treatment with CyA and nifedipine improved GFR to 1.13 +/- 0.34 ml min-1 g-1 kidney weight (gKW) (n = 19, P less than 0.05), as compared to CyA and placebo treated controls (n = 12, 0.83 +/- 0.32 ml min-1 g-1 KW). Nifedipine also reduced FPR (88.6 +/- 5.1% vs. 83.2 +/- 5.6%. P less than 0.01), and increased lithium clearance from 99 +/- 54 to 184 +/- 64 microliters min-1 g-1 KW (P less than 0.001). The results are further evidence that CyA nephrotoxicity includes renal vasoconstriction, and indicates that calcium entry blockade is nephroprotective in the case of CyA toxicity.     

Enhancement of cyclosporin A induced hepato- and nephrotoxicity by glutathione depletion

Abstract The role of glutathione in cyclosporin A (cyclosporin) hepato- and nephrotoxicity has not been clarified yet. The hypothesis that a glutathione deficit enhances the hepato- and nephrotoxicity of cyclosporin was tested in an animal model. Glutathione depletion was achieved by administration of diethyl maleate (DEM). Adult Sprague Dawley rats were divided into four groups (A–D; n≥ 8) and treated for 8 d as follows: group A, glucose 5% (0·4 ml kg^-1, i.p.) + 3 h later olive oil (0·5 ml kg^-1, oral); group B, DEM (0·4 ml kg^-1, i.p.) + 3 h later olive oil (0·5 ml kg^-1, oral); group C, glucose 5% (0·4 ml kg^-1, i.p.) + 3 h later cyclosporin (50 mg kg^-1, oral); group D, DEM (0·4 ml kg^-1, i.p.) + 3 h later cyclosporin (50 mg kg^-1, oral). Cyclosporin alone increased bilirubin concentration from 1·0 ± 0·6 μmol l^-1 to 8·4 ± 1·9 μmol l^-1 (P < 0·05) without changing transaminases. In glutathione depleted rats cyclosporin caused a further elevation of serum bilirubin up to 23·4 ± 5·5 μmol l^-1. This was accompanied by a 50% increase of serum glutamic oxaloacetic transaminase (GOT). Cyclosporin alone significantly decreased creatinine clearance to 50% of controls (P < 0·05). Cyclosporin treatment following glutathione depletion resulted in a further decline of creatinine clearance to 22% of controls. DEM had no effect on kidney or liver function. In conclusion glutathione depletion increases the susceptibility to cyclosporin-induced liver and kidney injury. The results support the hypothesis that sufficient cellular glutathione concentrations may be important to prevent cyclosporin-induced hepato- and nephrotoxicity.     

Abnormal glomerular and tubular function during angiotensin converting enzyme inhibition in renovascular hypertension evaluated by the lithium clearance method

Glomerular filtration rate (GFR) and tubular function were measured by means of the lithium clearance technique in 14 patients with renovascular hypertension (RVH) and eight patients with essential hypertension (EH) before and after oral administration of captopril 25 mg. In RVH captopril reduced 51-Cr-EDTA clearance (67.3 (median) to 47.5 ml min-1, P less than 0.01), proximal absolute reabsorption of fluid (53.9 to 41.5 ml min-1, P less than 0.01) and distal absolute reabsorption of sodium (2195 to 1402 mumol min-1, P less than 0.01), whereas proximal fractional reabsorption increased slightly (77.5 to 80.2%, P less than 0.02). In EH, however, these parameters were practically unaffected by captopril. In both RVH and EH plasma concentrations of angiotensin II and aldosterone were reduced after captopril, but atrial natriuretic peptide in plasma and urinary excretion rate of prostaglandin E2 were unchanged. Blood pressure decreased after captopril in both groups, but the maximum fall in systolic BP was more pronounced in RVH (22%) than EH (13%). It is concluded that angiotensin converting enzyme inhibition markedly reduced absolute reabsorption in both the proximal and distal tubules in RVH, in contrast to EH, predominantly due to fall in the GFR, and that the slight increase in proximal fractional reabsorption may be attributed to a reduction in the hydrostatic pressure in the peritubular vessels.     

Exaggerated natriuretic response to isotonic volume expansion in hypertensive renal transplant recipients: evaluation of proximal and distal tubular reabsorption by simultaneous determination of renal plasma clearanceof lithium and 51Cr-EDTA

In fourteen hypertensive and fourteen normotensive renal transplant recipients, and in a group of thirteen healthy controls, changes in natriuresis, glomerular filtration rate (GFR), and tubular reabsorption of sodium were determined in relation to intravenous infusion of 2 mmol isotonic sodium chloride per kg body weight. An exaggerated natriuresis was demonstrated in the hypertensive renal transplant recipients. This new finding indicates that the augmented natriuresis following plasma volume expansion, which is a characteristic finding in subjects with arterial hypertension, is not mediated by the renal nerves. Investigation of the tubular reabsorption rates of sodium by simultaneous determination of the renal clearance of 51Cr-EDTA and lithium showed that in the hypertensives the changes in tubular handling of sodium were different from those registered in the normotensive subjects. The increased sodium excretion in the hypertensive renal transplant recipients was caused by an increased output of sodium from the proximal tubules which was not fully compensated for by an increased distal reabsorption. Whether this increased delivery of sodium to the distal segments was caused by changes in GFR or in the proximal tubular reabsorption of sodium could not be clarified in the present study and warrants further investigations.     

Further studies on the mechanism of the natriuretic response to low-dose dopamine in man: effect on lithium clearance and nephrogenic cAMP formation

The effect of intravenous infusion of low-dose dopamine on electrolyte excretion, lithium clearance, nephrogenous cAMP formation and renal haemodynamics was investigated in healthy volunteers. Dopamine significantly increased the urine flow rate by 70.6% and urinary sodium excretion by 72%, but did not change creatinine clearance, PRA or plasma levels of AVP, ANP and cAMP. Renal plasma flow significantly increased by 48.6%; the glomerular filtration rate was not changed. Lithium per se increased basal PRA, but had no effect on the increments of urine flow rate, sodium excretion and renal blood flow induced by dopamine. Dopamine significantly increased the fractional excretion of lithium (representing fractional excretion of sodium at the proximal level). The increase in urinary sodium excretion during dopamine infusion, significantly correlated with the increase in fractional excretion of lithium (r = 0.94; P less than 0.01) and the increase in nephrogenous cAMP formation (r = 0.96; P less than 0.01). No correlation was found between the increase in urinary sodium excretion and the increase in renal blood flow. In conclusion, this study confirms that low-dose dopamine increases renal blood flow and urinary sodium excretion in healthy volunteers. This natriuretic response appears to be due to interaction with proximal tubular dopamine receptors, which are positively coupled to adenylate cyclase.     

Evaluation and comparison of therapeutic monitoring of whole-blood levels of cyclosporin A and its metabolites in renal transplantation by HPLC and RIA methods

Background: The aim of the work was to evaluate the possibility to estimate the level of cyclosporin A (CyA) metabolites as the difference of radioimmunoassay (RIA) non-specific and RIA specific methods. Methods: Blood samples of renal transplant patients were analyzed by three different methods: RIA specific method (CYCLO-Trac, DiaSorin, USA) (RIA_SP), RIA non-specific method (Immunotech, Czech Republic) (RIA_NS), and high performance liquid chromatography (HPLC) method. Results: Although values obtained by RIA_SP correlated well those obtained by HPLC (RIA_SP=0.995·HPLC+9.68; r²=0.962, n=448), the results of HPLC methods were lower by 8%. The values obtained by RIA_NS were 2.57 times higher than the values obtained by RIA_SP (RIA_SP=0.356RIA_NS; r²=0.713, n=448). The ratio (CyA+CyA metabolites)/(CyA) calculated as the ratio RIA_NS/RIA_SP values for 42 renal transplant patients was relatively stable for each particular patient. The sum of selected CyA metabolites (M1+M17+M21) measured by HPLC correlated well with that estimated from the difference of RIA_NS−RIA_SP: HPLC_metab=0.921·(RIA_NS−RIA_SP)+21.3; (r²=0.746, n=448). Conclusion: The combination of both the specific and non-specific methods for the determination of CyA presents an improved means for the TDM of CyA and CyA metabolites in renal transplant patients. Moreover, a combination of both methods can help to elucidate some unexpected events, such as the persistence of high cyclosporin blood levels.     

环孢菌素A治疗自身免疫性溶血性贫血和Evans综合征疗效观察

目的 探讨环孢菌素A（CsA)在自身免疫性溶血性贫血（AIHA）和Evans综合征的综合免疫抑制治疗中所起的作用。方法 前瞻性研究CsA合并传统方案（泼尼松 达那唑（18例）和单用传统方案（26例）治疗Coombs试验阳性的AIHA和Evans综合征的疗效。结果 CsA组3个月有效率为94.4%,平均起效时间为19.9d,完全缓解率为88.9%,其中进行长期随访的12例患者1年内仅1例复发（复发率3.3%）,2年内2例复发（复发率（16.7%),3年复发率仍为16.7%;而传统方案3个月有效率为92%,平均起效时间为23.2d,完全缓解率为100%。两组治疗有效率、平均起效时间差异无显著性,而完全缓解率CsA组显著高于传统方案组,3年内复发率CsA组明显低于传统方案组。结论 使用含CsA的综合免疫抑制方案治疗AIHA和Evans综合征可提高并巩因疗效。     

Enhanced renal production of cyclic GMP and reduced free water clearance during sodium nitroprusside infusion in healthy man

Abstract. A 90–min intravenous infusion of the direct vasodilator sodium nitroprusside (SNP) was compared with a placebo infusion in 32 healthy control subjects in order to study the acute effects of SNP on renal haemodynamics, tubular function evaluated by the lithium clearance technique, the plasma levels of atrial natriuretic peptide (ANP), angiotensin II (Ang II), aldosterone (Aldo) and arginine vasopressin (AVP) and the tubular transport of cGMP (T_cGMP). SNP infusion induced a significant reduction in mean arterial blood pressure (from 89.5 to 81.5 mmHg), urinary output (from 7.7 to 4.5 ml min^-1), free water clearance (from 4.0 to 1.3 ml min-^I) and ANP (from 3.3 to 2.5 pmoll-¹) and a significant increase in heart rate (from 57 to 64 beats min^-l), Ang II (from 11 to 18 pmoll^-1), Aldo (from 189 to 308 pmol L^-1) and in the tubular secretion of cGMP (T_cgmP from 28.8 to 214.4 pmol min^-1), (all values are medians and changes from baseline to 90 min after infusion start). Glomerular filtration rate, renal plasma flow, urinary sodium excretion, lithium clearance and plasma level of AVP were not significantly changed. It is concluded that SNP infusion in healthy subjects decreases urinary output and free water clearance without any change in sodium excretion, indicating a dissociation between the salt and water retaining effects of SNP in the early phase of treatment, probably due to an enhanced distal tubular water reabsorption of water. It is suggested that this increase in reabsorption of water in the distal parts of the nephron during SNP infusion may be mediated by an increase of cGMP production in the kidney, as indicated by the increase in T_cGMP during the SNP infusion.     

Natriuretic factors and lithium clearance in patients with the syndrome of inappropriate antidiuretic hormone (SIADH)

Because the syndrome of inappropriate antidiuretic hormone (SIADH) is a state of disturbed body fluid volume regulation and altered sodium balance we sought to determine if recently described volume regulatory factors were stimulated in SIADH. We measured atrial natriuretic peptide (ANP), endogenous digitalis-like natriuretic factor (EDNF) and urinary free dopamine in SIADH (n = 27). We also determined fractional clearance of lithium (FCLi). The data obtained in SIADH were compared with similar measurements performed in sodium retaining hyponatremias, such as those of heart failure (n = 26), liver cirrhosis (n = 19) and volume contraction (n = 28). We observed: ANP was 19.5 +/- 2.7 fM/ml in SIADH; it was significantly lower than ANP in cardiac failure, but no different from ANP in volume contraction. Urinary free dopamine was 2.2 +/- 0.8 microM/24 h in SIADH; this was significantly higher than in volume contraction and liver cirrhosis. EDNF (259 +/- 42 nM/24 h) and FCLi (21.4 +/- 2%) were both numerically higher in SIADH than in other hyponatremic disorders; however, the differences did not achieve significance. In conclusion, our observations did not establish a specific role of ANP in chronic stable SIADH. As to the importance of EDNF, dopamine and proximal tubular fluid reabsorption (FCLi) additional work using acute volume changes may demonstrate their participation in the renal sodium handling of SIADH more clearly than our study did.     

利培酮与碳酸锂治疗躁狂发作对照研究

目的比较利培酮与碳酸锂治疗躁狂发作的疗效及安全性。方法将80例躁狂发作患者随机分为利培酮组和碳酸锂组各40例．观察治疗4w,采用Bech-Rafaelsen躁狂量表及副作用量表评定疗效和不良反应并进行对比分析。结果利培酮组治疗1w末Rech-Rafaelsen躁狂量表总分比治疗前明显降低（P〈0．05）．且显著低于碳酸锂组（P〈0．05）;治疗4w末两组均显著低于治疗前（P〈0．01）．组间比较无显著性差异（P〉0．05）。副作用量表同期评定提示。利培酮组不良反应发生率较低,且程度较轻．患者耐受性好。结论利培酮治疗躁狂发作起效快,疗效肯定,不良反应较轻。治疗依从性好。     

Hepatocellular clearance function of bacterial lipopolysaccharides and free lipid A in mice with endotoxic shock

Hepatic uptake of bacterial lipopolysaccharides (LPS) in defined salt forms and free lipid A was studied in C3H mice. Extracts of ¹⁴C-labeled and unlabeled LPS from Salmonella abortus equi and lipid A from Salmonella minnesota R 595 (Re) were administered intravenously in doses sufficient to induce endotoxic shock. Sixty minutes after administration of ¹⁴C-LPS, 40% of the total activity was found in the liver tissue, 10% was in the isolated nonparenchymal cells, and only 1% was in the isolated hepatocytes. However, at this time only one third of the hepatocytes could be isolated; the other two thirds were obviously damaged. After 240 minutes, 55% of the total activity was measured in the liver tissue. The nonparenchymal cells had 8% of the activity, and all hepatocytes were damaged. By use of immunofluorescence, LPS S abortus equi was localized in sinusoidal cells 5 to 10 minutes after administration, and LPS S minnesota R 595 and lipid A were found in both nonparenchymal and parenchymal liver cells. All toxins were localized in both cell populations 60 and 240 minutes after injection. After application of LPS or lipid A, the third complement component (C3) was detectable in sinusoidal cells. In decomplemented mice the hepatic deposits of LPS and lipid A were unaffected, without demonstration of C3. The data indicate that LPS and lipid A interact in vivo with Kupffer cells and hepatocytes. Hepatic clearance of endotoxin seems to be independent of complement.     

A micropuncture study of renal phosphate transport in rats with chronic renal failure and secondary hyperparathyroidism.

Micropuncture studies were carried out in rats to determine changes in tubular transport of phosphate which occur in chronic renal failure and secondary hyperparathyroidism. Rats underwent subtotal nephrectomy (NX) and were fed a low calcium, high phosphorus diet for 3--4 wk. Other groups consisted of normal control animals, normal rats infused with sodium phosphate to raise filtered load of phosphate, subtotal NX rats parathyroidectomized (PTX) on the day of experiment, and normal PTX rats infused with sodium phosphate. It was found that filtered phosphate/nephron is markedly increased in subtotal NX rats due to high single nephron filtration rates, proximal tubular fluid plasma phosphate ratios are less than 1.0, and fractional reabsorption of phosphate is decreased in the proximal tubule. More phosphate was present in the final urine than in surface distal convoluted tubules. Acute PTX in subtotal NX rats resulted in a striking increase in proximal phosphate reabsorption, and urinary phosphate became approximately equal to that remaining in surface distal tubules. Phosphate loading in normal rats reduced fractional reabsorption in the proximal tubule, but urinary phosphate was not greater than that at the end of surface distal tubules. Acute PTX in normal phosphate-loaded animals had no significant effect on proximal tubular phosphate reabsorption. These observations suggest that phosphate homeostasis in chronic renal failure is acheived by inhibition of proximal phosphate reabsorption, counteracting a greatly enhanced intrinsic capacity for reabsorption. In addition, the large amount of urinary phosphate is consistent either with secretion by the collecting ducts or with a disproportionately high contribution by deep nephrons. The changes in phosphate transport are mediated by parathyroid hormone and are completely abolished by acute removal of the hormone.     

A prospective comparative study of gentamicin- and amikacin-induced nephrotoxicity in patients with normal baseline renal function

The aim of this study was to compare the nephrotoxic potential of amikacin (AK) and gentamicin (GM) in patients with normal baseline renal function. This study was a 1-year, non-interventional prospective study of patients administered either GM or AK. The study was carried out at the internal medicine department of Al-Watani governmental study. Nephrotoxicity was defined as a serum creatinine (SCr) increase of ≥0.5 mg/dL from the basal (normal) SCr level. The two groups (GM, n  = 45 and AK, n  = 49) were similar in population composition, and underlying pathological and infectious processes requiring antimicrobials. No significant difference in age was found between patients in the GM and AK groups, P  = 0.83. Patients in the GM group received comparatively lower doses than those in the AK group (mean = 2.5 mg/kg/day and 14.4 mg/kg/day, respectively) but the duration of treatment was similar. Sixteen of 45 patients receiving GM (35.6%) and eight of 49 patients receiving AK (16.3%) developed nephrotoxicity, P  = 0.033. Single daily dosing with GM, regardless of the total daily dose, produced less nephrotoxicity than multiple dosing. In contrast, AK given at a total dose of 1 g daily, showed no benefit of single dosing compared with multiple dosing. In patients with initial normal renal function, GM was significantly more nephrotoxic than AK. Multiple dosing of GM was more nephrotoxic than single dosing. AK-induced nephrotoxicity was not significantly dependent on dosing frequency.     

奎硫平与碳酸锂治疗双相障碍躁狂发作对照研究

目的 探讨奎硫平与碳酸锂治疗双相障碍躁狂发作的临床疗效和安全性. 方法 将84例双相障碍躁狂发作患者随机分为两组,各42例,研究组口服奎硫平治疗,对照组口服碳酸锂治疗,观察8周.于治疗前及治疗第1周、2周、4周、6周、8周末采用Beck-Rafaelsen躁狂量表及临床总体印象量表评定临床疗效,副反应量表评定不良反应. 结果 治疗后两组躁狂量表及临床总体印象量表总分均较治疗前显著下降（P＜0.01）,研究组治疗1周、2周末临床总体印象量表评分显著低于对照组（P＜0.01）,2周、4周末躁狂量表评分显著低于对照组（P＜0.05或0.01）;治疗8周末研究组显效率85.7%、总有效率95.24%,对照组分别为88.1%、95.24%,两组疗效无显著性差异（P＞0.05）.两组不良反应发生率无显著性差异（P＞0.05）. 结论 奎硫平治疗双相障碍躁狂发作疗效显著,且与碳酸锂相当,安全性高,但较碳酸锂起效更快,且不需常规监测血药浓度,更适合在基层社区应用.     

Impact of fraction unbound,CYP3A,and CYP2D6 in vivo activities,and other potential covariates to the clearance of tramadol enantiomers in patients with neuropathic pain

The pharmacokinetics of tramadol is characterized by a large interindividual variability, which is partially attributed to polymorphic CYP2D6 metabolism. The contribution of CYP3A, CYP2B6, fraction unbound, and other potential covariates remains unknown. This study aimed to investigate the contribution of in vivo activities of cytochrome P450 (CYP) 2D6 and 3A as well as other potential covariates (CYP2B6 genotype to the SNP g.15631G>T, fraction unbound, age, body weight, creatinine clearance) to the enantioselective pharmacokinetics of tramadol. Thirty patients with neuropathic pain and phenotyped as CYP2D6 extensive metabolizers were treated with a single oral dose of 100 mg tramadol. Multiple linear regressions were performed to determine the contribution of CYP activities and other potential covariates to the clearance of tramadol enantiomers. The apparent total clearances were 44.9 (19.1–102‐2) L/h and 55.2 (14.8–126.0) L/h for (+)‐ and (?)‐tramadol, respectively [data presented as median (minimum–maximum)]. Between 79 and 83% of the overall variation in apparent clearance of tramadol enantiomers was explained by fraction unbound, CYP2D6, and CYP3A in vivo activities and body weight. Fraction unbound explained 47 and 41% of the variation in clearance of (+)‐tramadol and (?)‐tramadol, respectively. Individually, CYP2D6 and CYP3A activities were shown to have moderate contribution on clearance of tramadol enantiomers (11–16% and 11–18%, respectively). In conclusion, factors affecting fraction unbound of drugs (such as hyperglycemia or co‐administration of drugs highly bound to plasma proteins) should be monitored, because this parameter dominates the elimination of tramadol enantiomers.     

环孢菌素A对肾血管性高血压大鼠心肌肥厚和心功能的影响 一项关于CaN对心肌肥厚及心功能影响的随机对照实验

目的通过建立两肾一夹高血压大鼠心肌肥厚模型,研究环孢菌素(CsA)对心肌肥厚及心功能的影响,以探讨钙调神经磷酸酶(CaN)在心肌肥厚进展中的作用。方法制备两肾一夹肾血管性高血压大鼠模型,术后2月,经心脏超声和部分大鼠(两肾一夹2月组)病理学证实心肌肥厚后,将大鼠随机分为两组,分别予生理盐水(两肾一夹3月组)或CsA(CsA组)腹腔注射,持续1月,并以假手术组作对照。观察大鼠左室重与胫骨长度比值、心肌细胞面积、左室后壁和室间隔厚度、CaN活性和心功能的改变。结果两肾一夹2月和3月组大鼠左室重与胫骨长度比值、心肌细胞面积、左室后壁和室间隔厚度较相应假手术组增高(F=12.4,13.0;P<0.05),CsA治疗组较两肾一夹2月和3月组均明显降低,与假手术组差异无显著性。CaN活性在两肾一夹2月和3月组均显著高于假手术组,CsA治疗后CaN活性下降(F=8.8;P<0.05)。各组射血分数、左室短轴缩短率及零负荷下等容收缩期心肌纤维收缩成分的缩短速度相似(F=1.0,1.1;P>0.05),CsA组左室舒张末压、等容舒张期压力下降时间常数较两肾一夹3月组显著下降(F=3.4,10,3;P<0.05)。结论CaN参与了肾血管性高血压心肌肥厚进展,CsA可逆转心肌肥厚,改善心脏舒张功能。     

Analysis of nutritive sucking function in very low and extremely low birthweight infants in Japan: A pilot study

Aim: The purpose of the present study was to investigate the differences in nutritive sucking patterns between very low, extremely low birth‐weight infants (LBWI) and full‐term infants (FTI) and to examine the change in those sucking patterns within 5 months after birth. Methods: Sucking patterns of eight LBWI and seven FTI were compared. In addition, sucking patterns were measured in four of the LBWI and seven of the FTI until 5 months of age to determine change in sucking wave patterns over time. Results: During the first month after birth, there was a significant difference in the sucking wave between the LBWI and FTI. The sucking cycle time was significantly shorter and the intensity of the sucking pressure was significantly smaller in the LBWI than that in the FTI. By 5 months, significant correlations were noted between the actual age or the modified age and the sucking pressure in both LBWI and FTI. Conclusions: The findings suggest that the weakness of oral muscular function and less sucking skill can bring about the weakness of intensity of sucking pressure, decreased time of the sucking stage in a sucking cycle, and unstable intensity of sucking pressure and time of the sucking stage in LBWI infants, causing low efficiency of milk intake and smaller amounts of milk swallowing during each sucking period as they obstructs the development of oral muscular function itself. These problems last for a longer period of time in LBWI than in FTI, leading to a deficit in the development of masticatory function in LBWI. The results of the current pilot study will serve as a foundation to investigate the development of masticatory function in LBWI as they grow into early childhood.     

人尿激酶原酶对心肌梗死大鼠血清淀粉样蛋白A和脂蛋白相关磷脂酶A2的影响分析

目的探讨与分析人尿激酶原酶对心肌梗死大鼠血清淀粉样蛋白A(SAA)和脂蛋白相关磷脂酶A2(LP-PLA2)的影响。方法 48只清洁级SD雄性大鼠购自北京维通利华公司,体重230 g左右,均给予建立心肌梗死模型。其中42只心肌梗死大鼠按照随机数字表法分为3组-模型组、实验1组、实验2组,每组各14只。实验1组、实验2组分别给予灌胃人尿激肽原酶1、2 mg/kg,模型组给予等量0.9%氯化钠溶液灌胃,1次/d,共4周。测定左心室舒张末期容积(LVEDV)、收缩末期容积(LVESV)、等容收缩期左心室内压力上升最大速率(d P/dt Max)与最小速率(d P/dt Min);计算心脏重量与大鼠体重比值(HW/BW)和心尖部心肌组织厚度;采用酶联免疫吸附试验法检测血清SAA和LPPLA2含量。结果实验1组、实验2组治疗第2周与第4周的LVEDV、LVESV均低于模型组,d P/dt Max与d P/dt Min值高于模型组,差异均有统计学意义(P <0.05),实验1组与实验2组对比差异无统计学意义(P>0.05)。实验1组、实验2组治疗第4周的心肌厚度与HW/BW比值均高于模型...