月桂氮酮及电穿孔技术对萘普生经皮渗透的影响

目的 :研究月桂氮艹卓 酮及电穿孔技术对萘普生经皮渗透的影响。方法 :应用双室扩散池方法研究促渗剂月桂氮艹卓 酮及电穿孔技术对萘普生在离体大鼠腹部皮肤经皮渗透的影响。结果 :电穿孔 (指数衰减型脉冲 ,脉冲幅度为 380V ,电容器电容为2 2 μF ,脉冲率为 4pulses·min 1,脉冲宽度τ≈ 5 .5ms ,脉冲数 10 0个 )、月桂氮 艹卓 酮预处理皮肤或两者合用均可显著促进萘普生的渗透速率和累积渗透量。两者合用的渗透速率与电穿孔或月桂氮 艹卓 酮预处理的渗透速率无显著差异。结论 :月桂氮 艹卓 酮预处理及电穿孔技术均能明显促进萘普生的经皮渗透 ,两者合用并无协同作用     

维拉帕米、硝苯吡啶对大鼠输卵管活动和卵转运的影响

钙拮抗剂维拉帕米(VER)和硝苯吡啶(NIF)可明显抑制离体大鼠输卵管标本的自发性收缩活动,用求积仪测得的5min收缩曲线面积表明:VER、NIF给药后面积均明显小于给药前,呈剂量依赖性,在整体实验中VER、NIF可使妊娠3d大鼠输卵管内卵的运行加速,与对照组比较,用药组在子宫腔内回收到的卵数明显多于对照组,合笼实验证明VER、NIF没有抗着床作用。     

THE EFFECTS OF HIGH Na AND Cl CONCENTRATIONS ON RAT PROXIMAL VOLUME AND Na FLUXES AT ZERO TUBULAR FLOW

1. In vivo micropuncture techniques, with and without peritubular capillary perfusion, were used to study the effects of high extracellular Na and Cl concentrations on transepithelial volume (Jv) and sodium (JNa) fluxes in rat proximal tubules. 2. In a double blind manner, the shrinking drop technique of Gertz was used to measure Jv; JNa was calculated from this and the tubular fluid Na concentration. 3. At both 184 and 279 mmol/l pericellular Na concentrations (both inside and outside the tubular epithelium), net Jv decreased significantly by 15 and 64%, respectively. Net JNa remained constant at 184 but decreased by 29% at 279 mmol/l Na concentration. 4. Thus, at both Na concentrations, when translated to free flow conditions, fractional Na reabsorption must have decreased. These findings, also supported by previous results at these Na concentrations, indicate that active Na transport was inhibited by high pericellular Na concentrations. 5. When intratubular Cl concentration was varied between 108 and 138 mmol/l while peritubular Cl was maintained constant (blood perfusing the capillaries), neither Jv nor JNa changed. Thus, at zero tubular flow, differential Cl/HCO3 concentrations do not provide significant driving forces for net Jv or JNa. 6. When only intratubular but not peritubular Na was elevated to 279 mmol/l, Jv and JNa increased markedly by 50 and 187%, providing evidence that a true solvent drag (solute drag) effect does exist in rat proximal tubules. 7. These findings offer a mechanism to explain why Na reabsorption is not increased when the filtered load of Na is increased with an elevation of plasma Na.(ABSTRACT TRUNCATED AT 250 WORDS)     

抗真菌药物的研究VI.C-端含MEDP的寡肽的合成和抗白念珠菌活性

目的：寻找高效低毒的抗真菌化合物。方法和结果：根据违法传递概念设计合成了１２个碳端含有ＭＥＤＰ（Ｎ３［（２Ｒ,３Ｒ）４ｍｅｔｈｏｘｙｅｐｏｘｙｓｕｃｉｎｙｌ］Ｌ２,３ｄｉａｍｉｎｏｐｒｏｐａｎｏｉｃａｃｉｄ）的二肽和三肽（１～１２）,均系新化合物。结论：体外抗白念珠菌实验表明：有些二肽三肽体外实验显示了较强的抑菌活性,其中ＶａｌＭＥＤＰ的活性最强,其ＭＭＩＣ为４５ｎｍｏｌ·ｍＬ－１,较母体ＭＥＤＰ提高９６０倍。     

硝苯吡啶对兔输卵管活动和卵子运行的影响

钙道阻断剂硝苯吡啶(NIF)可明显延缓卵子在兔输卵管内的运行速度。在HCG处理的麻醉兔,NIF抑制输卵管的自发收缩,并说明减弱去甲肾上腺素(NA)和15-甲基PGF_2α所致输卵管腔内压升高和电活动增强。在离体兔输卵管环肌标本,NIF能明显压低NA使峡部和壶腹部环肌张力提高的浓度—反应曲线。以上提示NIF延缓兔卵子运行可能与其阻断钙通道,抑制平滑肌收缩和/或降低输卵管平滑肌对内源性NA和PGF_2α的反应性有关。     

新吩嗪化合物K＿3－Ye的分离和结构鉴定

自一株基因工程链霉菌Ｋ３的发酵液中分离得到一吩嗪类新化合物，经光谱数据（ＵＬ，ＩＲ，１ＨＮＭＲ，１３ＣＮＭＲ，ＤＥＰＴ）分析，确定其结构为１－吩嗪氧基乙酸甲酯，代号Ｋ３－Ｙｅ。经初步测定它有较强的抗核苷转运活性。     

新吩嗪化合物K3-Ye的分离和结构鉴定

自一株基因工程链霉菌K₃的发酵液中分离得到一吩嗪类新化合物,经光谱数据(UL,IR,¹HNMR,¹³CNMR,DEPT)分析,确定其结构为1-吩嗪氧基乙酸甲酯,代号K₃-Ye。经初步测定它有较强的抗核苷转运活性。     

D—聚甘酯在各脏器的分布特点及其透过血脑屏障机制的研究

利用＾３Ｈ标记Ｄ－聚甘酯,观察了小鼠口服Ｄ－聚甘酯后在各组织和器官尤其是脑的分布特点,并对春血脑屏障的机制进行了初步探讨。实验结果显示,Ｄ－了矣甘酯可以迅速透过血脑屏障,并且除肾脏外,其在脑中的显著性地高于其他组织与器官。Ｄ－聚甘酯在中脑的２显著的高于脑的其他部位。给药３ｈ以后,脑内的Ｄ－聚甘酯９５．８％以原形存在。给小鼠等量的＾３Ｈ－Ｄ－聚甘酯和不同量的Ｄ－聚甘酯,随着Ｄ－聚甘酯量的增加,脑内的     

ERYTHROCYTE CATION FLUXES IN NORMAL AND HYPERTENSIVE HUMAN SUBJECTS

Intracellular cation concentrations ([Na]i, [K]i) and influxes of 22Na and 86Rb were determined in the erythrocytes of hypertensive and control groups of subjects. In both groups [Na]i showed a positive correlation with frusemide-resistant Na influx and was inversely correlated with ouabain-sensitive Rb influx, whereas [K]i was inversely correlated with frusemide-sensitive Na influx (FSNaI). No significant differences between groups were found in [Na]i, [K]i or frusemide-resistant Na influx. FSNaI was greater in males than females. FSNaI was slightly greater (P less than 0.06) in the hypertensive group, but the significance of the difference diminished with sex-matching. Ouabain-sensitive Rb influx was increased in the hypertensive group.     

含L-4-氧代赖氨酸寡肽的合成及其抗白念珠菌活性

本文运用“违法传送”概念,根据白念珠菌对寡肽的传送特点,设计并合成了十个含L-4-氧代赖氨酸(以下称I-677)的寡肽,以提高I-677的抗白念珠菌活性。体外抗白念珠菌试验表明:I-677-肽(I-677-X₁,I-677-X₁-X₂和I-677-X₁-X₂-Gly,其中X₁,X₂=Met,Leu,Ile,Ala,β-Ala,Gly)较I-677单体摩尔活性提高了2.1～28倍,其摩尔最低抑菌浓度为8.7×10^-8～9.3×10^-9mol/ml,传送肽和赖氨酸分别逆转I-677-肽抗菌活性的实验结果证实了I-677的“违法传送”途径。     

EFFECT OF EXERCISE ON GLUTAMINE SYNTHESIS AND TRANSPORT IN SKELETAL MUSCLE FROM RATS

• 1 Reductions in plasma glutamine are observed after prolonged exercise. Three hypotheses can explain such a decrease: (i) high demand by the liver and kidney; (ii) impaired release from muscles; and (iii) decreased synthesis in skeletal muscle. The present study investigated the effects of exercise on glutamine synthesis and transport in rat skeletal muscle.
• 2 Rats were divided into three groups: (i) sedentary (SED; n = 12); (ii) rats killed 1 h after the last exercise bout (EX‐1; n = 15); and (iii) rats killed 24 h after the last exercise bout (EX‐24; n = 15). Rats in the trained groups swam 1 h/day, 5 days/week for 6 weeks with a load equivalent to 5.5% of their bodyweight.
• 3 Plasma glutamine and insulin were lower and corticosterone was higher in EX‐1 compared with SED rats (P < 0.05 and P < 0.01, respectively). Twenty‐four hours after exercise (EX‐24), plasma glutamine was restored to levels seen in SED rats, whereas insulin levels were higher (P < 0.001) and costicosterone levels were lower (P < 0.01) than in EX‐1. In the soleus, ammonia levels were lower in EX‐1 than in SED rats (P < 0.001). After 24 h, glutamine, glutamate and ammonia levels were lower in EX‐24 than in SED and EX‐1 rats (P < 0.001). Soleus glutamine synthetase (GS) activity was increased in EX‐1 and was decreased in EX‐24 compared with SED rats (both P < 0.001).
• 4 The decrease in plasma glutamine concentration in EX‐1 is not mediated by GS or glutamine transport in skeletal muscle. However, 24 h after exercise, lower GS may contribute to the decrease in glutamine concentration in muscle.

     

REDUCED LUNG WATER TRANSPORT RATE ASSOCIATED WITH DOWNREGULATION OF AQUAPORIN-1 AND AQUAPORIN-5 IN AGED MICE

• 1 The purpose of the present study was to examine lung water transport properties and the expression and regulation of the alveolar endothelial water channel aquaporin (AQP)‐1 and the epithelial water channel AQP‐5 in aged mouse lung using gene expression analysis and water permeability measurements.
• 2 In aged (20–24‐month‐old) mice, AQP‐1 and AQP‐5 mRNA expression decreased by 55.5 and 50.3%, respectively, compared with that in young (8–10‐week‐old) mice (P < 0.01). In addition, AQP‐1 and AQP‐5 protein expression decreased in aged mice by 36.9 and 44.6%, respectively, compared with that in young mice (P < 0.01).
• 3 The osmotically driven water transport rate between the airspace and capillary compartments was reduced by 31.7% in aged mice compared with young mice (2.8 ± 0.3 vs 4.1 ± 0.3 mg/s, respectively; P < 0.01). The hydrostatically driven lung water accumulation rate in response to a 10 cmH₂O increase in pulmonary artery pressure was also reduced in aged mice by 21.9% compared with young mice (0.32 ± 0.06 vs 0.41 ± 0.04 mg/s, respectively; P < 0.01).
• 4 There was a 62.7% decrease in serum glucocorticoids in aged mice compared with young mice (67.6 ± 26.8 vs 181.3 ± 44.4 nmol/L, respectively; P < 0.01). In vivo administration of dexamethasone (4 mg/kg) for 5 consecutive days to aged mice increased lung AQP‐1 mRNA and protein expression by 2.1 ± 0.1 fold (P < 0.01) and 1.8 ± 0.2 fold (P < 0.01), respectively. Accordingly, osmotically and hydrostatically driven water transport rates increased by 35.6% (P < 0.01) and 31.2% (P < 0.01), respectively.
• 5 The present study provides the first evidence of altered lung water transport associated with downregulation of AQPs in aged lung. Blood glucocorticoid hormone levels are important to maintain normal AQP‐1 expression in the lung microvascular endothelium. Corticosteroid‐induced AQP‐1 upregulation may contribute to the role of corticosteroids in accelerating oedema clearance in aged lung.

     

EFFECTS OF TORASEMIDE ON RENAL HAEMODYNAMICS AND FUNCTION IN ANAESTHETIZED DOGS

1. We examined the effects of torasemide (0.3 and 1 mg/kg i.v.) on renal haemodynamics and function employing renal clearance and stop-flow techniques in anaesthetized dogs and compared these with furosemide (1 and 3 mg/kg i.v.). 2. Torasemide and furosemide did not influence renal haemodynamics, in the renal clearance study, but caused a dose-related and significant increase in urine flow and urinary excretion of sodium and potassium. Torasemide and furosemide increased fractional excretion of sodium in the distal tubules with a relatively small increase in the fractional excretion of lithium (index of sodium excretion at the proximal tubules, FELi). The diuretic profile of torasemide was of long duration, compared with that of furosemide. 3. Torasemide and furosemide inhibited sodium reabsorption at the distal portion of the tubules in the stop-flow study. 4. It is suggested from these results, that the main diuretic site of action of torasemide is the ascending limb of the loop of Henlé.     

INHIBITION OF K+ TRANSPORT IN HUMAN SICKLE CELL ERYTHROCYTES BY OKADAIC ACID AND SODIUM FLUORIDE

1. The effect of okadaic acid and sodium fluoride on swelling-and N-ethylmaleimide (NEM)-stimulated KC1 cotransport was examined in blood cells from homozygote sickle cell anaemia patients. 2. Blood was drawn into heparin or EDTA by vein puncture from sickle cell patients previously diagnosed in the haematology clinics of Princess Badee'a Teaching Hospital. A standard method for measuring flux by using radioactive rubidium was used. 3. Okadaic acid strongly inhibited swelling-stimulated KC1 cotransport if added before swelling. Okadaic acid and sodium fluoride added before NEM inhibited the activation of transport by NEM. Okadaic acid added after NEM did not inhibit transport. 4. The inhibition of the effects of NEM by okadaic acid and sodium fluoride indicates that activation of the flux by NEM requires the action o. phosphatase.     

EFFECT OF BLOOD FLOW AND HAEMATOCRIT ON THE RELATIONSHIP BETWEEN MUSCLE VENOUS Po2 AND OXYGEN UPTAKE IN DOG MAXIMALLY CONTRACTING GASTROCNEMIUS IN SITU

1. To clarify the limiting factors for peak V?o₂ (V?o_2peak)> we measured muscle venous Po₂ (Pvo₂) and V?o_{2, peak} under various O₂ delivery conditions (arterial O₂ concentration X flow) via the alteration of blood flow and haematocrit (Hct) in anaesthetized dog gastrocnemius muscle (n= 11) stimulated by 1 Hz isometrically and tetanically. 2. Two levels of flow (high and moderate) were maintained by using a pump (ISO and 100 mL/min per 100 g, respectively). Haematocrit was adjusted to 45 and 30% by isovolaemic haemodilution with dextran (MW 40 000). 3. The decrease in Hct induced a 31% decrease in O₂ delivery (P<0.05), a 9–12% decrease in Pvo₂, a 23% decrease in V?o_{2, peak}(P<0.05) and a 12–14% increase in O₂ extraction (V?o₂/O₂delivery) at both flow levels. The decrease in flow induced a 24–25% decrease in O₂ delivery (P<0.05), a 15–17% decrease in P_vo2 (P<0.05), a 9% decrease in V?o_2,peak (P<0.05) and a 19–22% increase in O₂ extraction (P<0.05) at both Hct levels. 4. The results suggest that the limiting factor of V?o_2peak, unrelated to O₂ diffusion limitation (i.e. the change in the heterogeneity of V?o₂ to O₂ delivery ratio among capillaries), due to lowering Hct may be different from that due to lowering blood flow in maximally contracting muscle.     

Renal Transport of Drugs: An Overview of Methodology with Application to Cimetidine

The development of new methods to study transport processes in renal epithelia has greatly enhanced our knowledge of the mechanisms involved in the transport of a number of endogenous compounds. More recently, these methods have been applied to study mechanisms of specific drug transport. This article is intended to provide an overview of the various methods used to study renal elimination of compounds. References to more detailed reviews of the individual methods are provided. Studies of the renal transport of cimetidine, a histamine H₂-receptor antagonist, are presented to illustrate the application of these methods to the study of specific drugs. Methods such as clearance techniques and the Sperber chicken preparation used to study renal elimination of compounds in whole animals are briefly described. Techniques to identify the site of renal transport including stop flow, isolated perfused tubules, and micropuncture methods are discussed and references to more technical reviews are cited. The more recently developed methods of isolated membrane vesicles for studying transport across the individual polar membranes of the proximal tubule are discussed along with the relevant studies of the use of these membranes in elucidating the mechanisms involved in the renal transport of cimetidine. Finally, the use of cultured renal epithelial cell lines in studying renal transport is described. Knowledge of drug transport mechanisms in the kidney is important both in drug targeting to the kidney and in understanding the pharmacokinetics of renally eliminated drugs. As exemplified by the studies with cimetidine, only by combining the data from experiments using diverse methodology can the mechanisms involved in the renal excretion of compounds be delineated. With the use of existing methods and the development of new technologies, many of the questions related to drug transport mechanisms can be addressed.     

The effect of naringenin on the intestinal and renal transport of organic solutes

Summary Naringenin (4,5,7-trihydroxy-flavanone) inhibits the accumulation of glycine, -methyl-glucoside, p-amino-hippurate and N¹-methyl-nicotinamide in dog renal cortex slices. It also inhibits oxygen consumption by this tissue. Since the sensitivity of amino-acid uptake to the drug is less than the sensitivity of oxygen consumption, the inhibition of this transport might be secondary to an effect on intermediary metabolism. The inhibition of PAH uptake occurs at a lower concentration of the drug, and so naringenin may affect this process at the membrane level.Naringenin inhibits the transport of sugars and amino-acids by dog, guinea-pig and rat small intestine. Both steady-state accumulation and initial rates of entry are affected. Amino-acid uptake is depressed both in the presence or absence of sodium ions. The inhibition is reversible provided short contact times are employed. According to kinetic analysis, naringenin appeared to be a fully non-competitive inhibitor of phenylalanine influx. Examination of the unidirectional transmural fluxes of phenylalanine across guinea-pig intestine revealed that only the mucosal-serosal flux was affected, and then only if the flavanone was added to the solution bathing the mucosal face of the tissue. Naringenin does not inhibit mucosal Na⁺-K⁺-ATPase, but it does alter the intracellular ion concentrations.Although some of the results can be explained in terms of an effect of naringenin on metabolism, others can not. It is argued that naringenin has a direct action on cell membranes.Some of these results have been presented to the Physiological Society and a short report has appeared in their proceedings (Robinson, 1979)     

PRIMARY ACTIVE TRANSPORT OF PROVASTATIN ACROSS THE LIVER CANALICULAR MEMBRANE IN NORMAL AND MUTANT EISAI HYPERBILIRUBINAEMIC RATS

We have previously demonstrated that the HMG-CoA reductase inhibitor pravastatin is efficiently taken up by the liver via the ‘multispecific anion transporter’ in an active manner.³ To further examine the fate of pravastatin within the liver, its biliary excretion was studied in a single-pass liver perfusion system and isolated liver canalicular membrane vesicles (CMVs) using normal (Sprague–Dawley rats; SDRs) and mutant Eisai hyperbilirubinaemic rats (EHBRs). In the liver perfusion experiments, the outflowing drug concentration reached a steady state at 30 min and the extraction ratio was approximately 0·7 in both rat strains. Both the steady state biliary excretion rate and bile flow rate of the EHBR group were 40% of those of SDRS. At steady state, the fraction of unchanged drug in bile was 25–34% in both groups. The concentration ratios of unbound drug in cytosol versus that in sinusoid and of that in bile versus that in cytosol were, respectively, 11 and 87 in SDRs, and 13 and 94 in EHBRs. After correction for the membrane potential (−40 mV in cytosol), the ratios became 49 and 19 in SDR and 58 and 21 in EHBRs, respectively. The finding that all of these values were much larger than unity suggested that active transport occurred from liver to bile, as well as from plasma to liver, in both rat strains. Furthermore, ATP-dependent uptake of pravastatin was clearly observed in CMVs prepared from EHBRs as well as SDRs, whereas the stimulation by ATP of DNP-SG transport in CMVs was observed only in SDRs. It was concluded that pravastatin is excreted into bile in high concentrations and a primary active transport mechanism which is maintained in EHBRs contributes to the biliary excretion of this drug.     

基层医院小儿危重症的急救转运128例报道

目的探讨基层医院急救转运模式及方法,提高本地区危重患儿的抢救成功率,降低危重患儿死亡率及致残率。方法对丰顺县人民医院近3年来转运的危重患儿128例进行回顾性分析。结果全部危重病患儿均安全转运至上级医院相应专科病房,在转运患儿的原发病以新生儿疾病、重症肺炎和各种感染为主,无1例在途中发生意外或死亡。结论加强转运前、转运途中质量控制,充分估计病情变化,密切监测病情是安全转运的前提条件,快捷安全的转运,提高了本地区危重患儿的抢救成功率,降低危重患儿死亡率及致残率是非常有效的。