Role of Medical Approach in the Management of Stone Disease

In the management of stone disease, the medical approach concerned with the prevention of stone recurrence is equally as important as the surgical removal of stones. The application of medical approach requires an understanding of the pathophysiology of stone formation. A wide variety of physiological or environmental disturbances have been identified in stone–forming patients. They include hypercalciuria, hypocitraturia, undue urinary acidity and hyperuricosuria. Reliable diagnostic protocols have been developed which are based on the presence of above derangements. The prophylactic treatment programs are directed at the correction or amelioration of underlying environmental disturbances. Conservative measures include a high fluid intake, dietary sodium and oxalate restriction, dietary calcium restriction (in absorptive hypercalciuria and primary hyperparathyroidism), and moderate animal protein restriction. Specific medical treatments chosen for discussion are thiazide, slow–release neutral potassium phosphate, potassium citrate and potassium magnesium citrate.     

Ion channel expression by white matter glia: I. Type 2 astrocytes and oligodendrocytes

White matter is a compact structure consisting primarily of neuronal axons and glial cells. As in other parts of the nervous system, the function of glial cells in white matter is poorly understood. We have explored the electrophysiological properties of two types of glial cells found predominantly in white matter: type 2 astrocytes and oligodendrocytes. Whole-cells and single-channel patch-clamp techniques were used to study these cell types in postnatal rat optic nerve cultures prepared according to the procedures of Raff et al. (Nature, 303:390-396, 1983b). Type 2 astrocytes in culture exhibit a "neuronal" channel phenotype, expressing at least six distinct ion channel types. With whole-cell recording we observed three inward currents: a voltage-sensitive sodium current qualitatively similar to that found in neurons and both transient and sustained calcium currents. In addition, type 2 astrocytes had two components of outward current: a delayed potassium current which activated at 0 mV and an inactivating calcium-dependent potassium current which activated at -30 mV. Type 2 astrocytes in culture could be induced to fire single regenerative potentials in response to injections of depolarizing current. Single-channel recording demonstrated the presence of an outwardly rectifying chloride channel in both type 2 astrocytes and oligodendrocytes, but this channel could only be observed in excised patches. Oligodendrocytes expressed only one other current: an inwardly rectifying potassium current that is mediated by 30- and 120-pS channels. Because these channels preferentially conduct potassium from outside to inside the cell, and because they are open at the resting potential of the cell, they would be appropriate for removing potassium from the extracellular space; thus it is proposed that oligodendrocytes, besides myelinating axons, play an important role in potassium regulation in white matter. The conductances present in oligodendrocytes suggest a "modulated Boyle and Conway mechanism" of potassium accumulation.     

Enhancement of blood-brain barrier permeability to sodium fluorescein by stimulation of µ opioid receptors in mice

Summary The effects of opioids on the permeability of the blood-brain barrier (BBB) were examined in mice with sodium fluorescein as an indicator of the permeability. The brain was perfused with saline 30 min after injection of sodium fluorescein (40 mg/kg, i. v.) and examined by fluorometry. Morphine hydrochloride (0.3–10 mg/kg, s. c.) markedly increased the brain level of sodium fluorescein dose-dependently without influencing the plasma level, when administered 20 min before sodium fluorescein injection. Intracerebroventricularly (i. c. v.) injected morphine hydrochloride (0.5 and 1.0 Erg) increased the brain sodium fluorescein level. Buprenorphine (0.1 and 0.5 mg/kg, s. c.) was also effective. However, pentazocine, ethylketazocine, U-50488H and SKF-10047 had no significant influence. The i.c.v. administration of [D-Ala², McPhe⁴, Gly(ol)⁵]enkephalin (0.1 g) and [D-Ala², D-Leu⁵]enkephalin (0.5 g) but not of [D-Thr², Leu⁵]enkephalin-Thr increased the brain level of sodium fluorescein significantly. A small dose of naloxone (i. p.) significantly inhibited the effects of morphine, buprenorphine, [D-Ala², McPhe⁴, Gly(ol)⁵]enkephalin and [D-Ala³, D-Leu⁵]enkephalin. ICI-174864 co-administered i. c. v. with [D-Ala², D-Leu⁵]enkephalin was ineffective in antagonizing the effect of the latter. These findings suggest that the stimulation of µ opioid receptors results in an increase in BBB permeability to sodium fluorescein. Send offprint requests to K. Saeki     

Frailty评分对枸橼酸伊沙佐米治疗多发性骨髓瘤不良反应的预测价值

目的 探讨Frailty评分对枸橼酸伊沙佐米治疗多发性骨髓瘤(multiple myeloma, MM)不良反应的预测价值。方法 选取MM患者72例,均予以枸橼酸伊沙佐米联合沙利度胺、地塞米松方案治疗,观察治疗效果及不良反应。并根据患者不良反应程度分为Ⅰ～Ⅱ级组和Ⅲ～Ⅳ级组。比较2组Frailty评分;采用Cox回归模型分析化疗相关Ⅲ～Ⅳ级不良反应的影响因素;采用ROC曲线模型分析Frailty评分对化疗相关Ⅲ～Ⅳ级不良反应的预测价值。结果 72例MM患者均实施枸橼酸伊沙佐米治疗,总有效率为80.55%;出现不良反应70例、以乏力占比最高,发生率为72.22%,其次为淋巴细胞降低25.00%、贫血18.06%,未出现任何不良反应2例。Ⅲ～Ⅳ级组Frailty评分高于Ⅰ～Ⅱ级组(P<0.05)。70例出现不良反应患者均随访12个月,其平均生存时间(22.30±2.28)个月。Cox回归分析结果显示,Frailty评分≥2分是MM患者发生Ⅲ～Ⅳ级不良反应的影响因素。ROC曲线分析显示,Frailty评分预测化疗相关Ⅲ～Ⅳ级不良反应AUC值为0.925(95%CI:0.816～1.00...     

The effect of harmaline on intestinal sodium transport and on sodium-dependentd-glucose transport in brush-border membrane vesicles from rabbit jejunum

Harmaline inhibition of sodium uptake and of sodium-dependentd-glucose transport was investigated using brush-border membrane vesicles from frozen rabbit jejunum. Under sodium-gradient conditions, initiald-glucose uptake (20 s) was inhibited by harmaline at concentrations above 0.5 mM, but at lower harmaline concentrationsd-glucose uptake was stimulated by 10–15%. When a similar potassium gradient was used, harmaline had no effect. At concentrations upt to 2 mM, harmaline did not alter the equilibrium uptake ofd-glucose ord-mannitol. After pre-equlibration with sodium (25 mM),d-glucose uptake was inhibited at harmaline concentrations ranging from 0.1 to 2 mM. Sodium (10 mM) uptake was also inhibited by harmaline. Increasing the sodium concentration reduced the inhibitory effect of harmaline on tracer sodium uptake as well as on sodium-dependentd-glucose uptake. Similar to phlorizin, harmaline (1 mM) was able to prevent glucose-induced sodium influx across the brush-border membrane.Sodium uptake into brush-border membrane vesicles seems to be inhibited at lower harmaline concentrations than sodium-dependentd-glucose uptake. At high (2 mM) inhibitor concentrations, however, sodium-dependent glucose uptake is more strongly inhibited than sodium uptake. These results suggest that harmaline inhibits both sodium and sodium-dependent transport across intestinal brush-border membranes by interacting with specific sodium-binding sites.     

Plasma levels of atrial natriuretic peptide are raised in essential hypertension during low and high sodium intake

Summary Plasma levels of -human atrial natriuretic peptide (hANP) were measured in 17 patients with primary hypertension (11 females, 6 males, aged 22–61; blood pressure systolic 154±7 mmHg, diastolic 92±4 mmHg) and in 9 normotensive controls (4 males, 5 females, aged 20–71; blood pressure systolic 117±4 mmHg, diastolic 76±2 mmHg) during unrestricted sodium diet, at the 4th day of a low sodium intake (40–60 mEq/day) and at the 6th day of sodium loading (280–320 mEq/day) both after an overnight rest and after 4 h of upright posture. In the controls, plasma levels of hANP at 8:00 a.m. were lowered from 73±11 to 49±7 pg/ml during low sodium diet and increased to 128±37 pg/ml after high salt intake. Plasma ANP levels were significantly lower after 4 h of upright posture during unrestricted, low and high sodium intake. In the hypertensive group, plasma ANP levels were elevated during unrestricted diet (203±43 pg/ml), during the low sodium period (139±31 pg/ml), and after high sodium intake (267±63 pg/ml) compared to the controls. All levels were lowered by upright posture. The absolute decrease was more pronounced compared to the normotensives, the relative decline was similar in both groups. In the hypertensives, plasma ANP levels significantly correlate with systolic and diastolic blood pressure (r=0.468,r=0.448,P<0.05) and with urinary aldosterone during unrestricted diet (r=0.536,P<0.05). There was an inverse correlation between plasma ANP levels and plasma renin concentration during low and high sodium intake (r=–0.469,r=–0.496,P<0.05).These studies demonstrate raised circulating plasma ANP levels in patients with essential hypertension. The modulation of ANP by different sodium intake and by upright posture is maintained similar to the changes in plasma ANP in normotensive controls. Raised ANP levels in the hypertensives are correlated with low renin secretion and high aldosterone excretion. High ANP levels, therefore, might indicate sodium retention in essential hypertension.Abbreviation ANP atrial natriuretic peptide Supported by a grant from Ministerium für Wissenschaft und Forschung, NRW     

Control of feeding during saline consumption and fluid deprivation in hamsters

Cellular dehydration induced by water deprivation or hypertonic saline injection reduces feeding in a variety of species. Normal feeding in rats is maintained during isotonic saline consumption by increasing the intake of saline compared to the usual intake of water. Hamsters do not show the spontaneous preference for isotonic saline noted in rats, even after adrenalectomy. In the present investigation, feeding by hamsters was depressed during both isotonic and hypertonic saline consumption compared to the usual feeding with water. Saline intakes did not exceed water intakes under similar conditions. When fluid intakes were elevated by prior fluid deprivation, feeding rates increased at all concentrations of saline after a delay proportional to the osmolality of the solution. Positive 24-hr sodium balances were always associated with saline consumption. Water and hypertonic saline injections reduced feeding, and the fluid loads were excreted very slowly. When hamsters were fluid deprived prior to injections, saline totally suppressed feeding, while water increased feeding compared to sham injected controls. It is concluded that cellular dehydration produces a reduction of feeding in hamsters drinking isotonic or hypertonic saline. Reduced feeding with isotonic saline consumption results from the failure of hamsters to increase their ad lib intake of that solution. The prolonged retention of both sodium and fluid after saline consumption or injection suggests that further saline intake may be inhibited by an expansion of the extracellular space.     

Sodium bicarbonate secretion indicated by ultrastructural cytochemical localization of HCO3 −, Cl−, and Na+ ions on rat bile duct brush cells

Brush cells are widely distributed in the digestive and respiratory apparatus, but their function is still unknown. Because brush cells (BC) are found in organs secreting NaHCO₃, it was hypothesized that these cells may secrete NaHCO₃. To test this possibility, rat common bile duct epithelia were examined by ultrastructural cytochemical methods for localizing HCO₃⁻, Cl⁻, and Na⁺ ions. All three ion precipitates were few in or on BCs of rats without stimulation. Lead carbonate precipitates, which localized HCO₃⁻ ions by the lead nitrate-osmium method, increased markedly on the surface of the microvilli (MV) of BCs after secretin or meal stimulation, but similar precipitates were few on the luminal surface of principal cells (PCs). Silver chloride precipitates, which indicate the presence of Cl⁻ ions by the silver-osmium method, increased in the apical cytoplasm and in MV of BCs after secretin or meal stimulation, but they were few in PCs. Sodium pyroantimonate precipitates, which localize Na⁺ ions by the potassium pyroantimonate-osmium method, increased on the surface of the MV, along the basolateral membrane, and in the apical cytoplasm of BCs after secretin or meal stimulation, but they were few in PCs. These results strongly suggest that BCs may be a significant source of NaHCO₃ secretion.     

Primary sequence and functional expression of a novel β subunit of the P-ATPase gene family

The cortical collecting tubule (CCT) of the mammalian kidney reabsorbs sodium and potassium, processes that are mediated by Na/K-ATPase and H/K-ATPase. CCT is also an important site for proton secretion, which is driven, in part, by H/K-ATPase. Na/K-ATPase and H/K-ATPase are members of the ion-motive P-ATPase gene family. They are closely related plasma membrane proteins which consist of heterodimers. The urinary bladder of the toad Bufo marinus is the amphibian counterpart of mammalian CCT. We have previously characterized a ouabain-resistant Na/K-ATPase [see ref. 17], from TBM cells, a clonal cell line derived from the toad bladder, which expresses transepithelial sodium transport. In the present study, we report the primary sequence and functional expression of a novel subunit ( _bladder= _bl) isolated from a toad bladder epithelial cell cDNA library. The deduced polypeptide is 299 amino acids in length and has a predicted molecular mass of 33 kDa. The _bl protein exhibits 35% amino acid identity to the previously characterized ₁ of B. marinus Na/K-ATPase and 39% identity with ₃ of B. marinus Na/K-ATPase. It shares 38% identity with the mammalian gastric H/K-ATPase and 52% with the mammalian ₂ Na/K-ATPase. Northern blot analysis shows that a 1.4×10³-base mRNA is expressed at a high level in bladder epithelial cells and eye and at a trace level in kidney; it is not detectable in significant amounts in the stomach, colon and small intestine. The _bl subunit can associate with the ₁ subunit of B. marinus Na/K-ATPase to form a functional sodium pump in the Xenopus laevis oocyte. Our data indicate that, in addition to the known ₁ and ₃ isoforms, a third distinct isoform of the subunit is present in the bladder epithelium. This new isoform could be functionally associated with subunits of either Na/K- or H/K-ATPase.