The effect of high animal protein intake on the risk of calcium stone-formation in the urinary tract

1. Studies were carried out on six normal male subjects to determine the short-term effect of increasing the dietary consumption of animal protein on the urinary risk factors for stone-formation, namely, volume, pH, calcium oxalate, uric acid and glycosaminoglycans. 2. An increase of 34 g/day of animal protein in the diet significantly increased urinary calcium (23%) and oxalate (24%). Total urinary nitrogen increased by an average of 368 mmol/day. The accompanying increase in dietary purine (11 mmol of purine nitrogen/day) caused a 48% increase in the excretion of uric acid. 3. The overall relative probability of forming stones, calculated from a combination of the risk factors, was markedly increased (250%) throughout the period of high animal protein ingestion.     

Human llamas: adaptation to altitude in subjects with high hemoglobin oxygen affinity.

To assess the adaptive value of the right-shift of the oxyhemoglobin dissociation curve (decreased affinity for oxygen) observed in humans upon altitude exposure, the short-term physiologic responses to altitude-induced hypoxia were evaluated in two subjects with a high oxygen affinity hemoglobin (Hb Andrew-Minneapolis) and in two of their normal siblings. In striking contrast to normal subjects, at moderately high altitude (3,100 m) the high affinity subjects manifested: (a) lesser increments in resting heart rate; (b) minimal increases in plasma and urinary erythropoietin; (c) no decrement in maximal oxygen consumption; and (d) no thrombocytopenia. There was no difference between subject pairs in 2,3-diphosphoglycerate response to altitude exposure. These results tend to contradict the belief that a decrease in hemoglobin oxygen affinity is of adaptive value to humans at moderate altitudes. Rather, they support the hypothesis that, despite disadvantages at low altitude, a left-shifted oxyhemoglobin dissociation curve may confer a degree of preadaptation to altitude.     

A novel GT-mismatch binding protein that recognizes strict DNA sequences with high affinity

Mismatched or damaged base pairs in DNA are mutagenic and both eukaryotes and prokaryotes have a series of repair systems that decrease a spontaneous mutation rate. All exocyclic amino groups of cytosine(C), adenine(A), and guanine(G) contribute to hydrogen bonds for base pairing. High temperature and oxidative stresses increase the deamination of these bases and methylated C. These deaminated sites would be initially recognized by components of DNA repair system. We discovered a novel G/thymine(T)-mismatch binding protein (nGTBP) that bound, with high affinity, to a minimal 14-mer DNA heteroduplex with a strict 5'-TRT GNB-3' sequence (R for purine, N for any bases, and B for "not A," namely for C, G, or T ). This italicized G position mismatched with T could be replaced by hypoxanthine, the deaminated A. The nGTBP, however, barely recognized DNA duplexes individually containing 8-oxo-G, thymine glycol, and 5-methylcytosine.     

Neuromedin B binds with high affinity, elevates cytosolic calcium and stimulates the growth of small-cell lung cancer cell lines.

Previously, gastrin-releasing peptide (GRP) receptors were identified on small-cell lung cancer (SCLC) cells and GRP functioned as a SCLC autocrine growth factor. Here the effects of neuromedin B (NMB) on SCLC cells were investigated. [125I-Tyr0]NMB bound with high affinity to three of seven SCLC cell lines examined. [125I-Tyr0]NMB bound to SCLC cell line NCI-H209 and NCI-H345 in a time-dependent and reversible manner. [125I-Tyr0]NMB bound with high affinity (Kd = 1 nM) to a single class of sites (Bmax = 800/cell). Specific [125I-Tyr0]NMB binding was inhibited with high affinity by NMB (IC50 = 1 nM) and moderate affinity by bombesin, GRP and [D-Arg1, D-Pro2, D-Trp7,9, Leu11]substance P ([APTTL]SP) but not GRP1-16 (IC50 = 50, 100, 1,000 and > 10,000 nM, respectively). In Fura 2 AM loaded NCI-H345 cells, NMB elevated cytosolic calcium in a concentration-dependent manner. NMB (10 nM) elevated the cytosolic calcium from 150 to 180 nM and calcium was released from intracellular pools. The increase in cytosolic calcium caused by 10 nM NMB was reversed by 1 microM [APTTL]SP but not 1 microM [D-Phe6]bombesin6-13methylester, a GRP receptor antagonist. Also, NMB stimulated the clonal growth of NCI-H209 and NCI-H345 in a concentration-dependent manner. The increase in the clonal growth caused by NMB was reversed by 1 microM [APTTL]SP. These data suggest that NMB receptors may regulate the proliferation of some SCLC cells.     

Human N-acetylation genotype determination with urinary caffeine metabolites

The human acetylation genotype was determined by measuring urinary caffeine metabolites by use of a modification of a previously published HPLC method. The problem of separation of 7-methylxanthine (7X) from 1-methyluric acid (IU) in urine extracts was achieved by adding a phenyl column, in tandem with a C18 reverse-phase column, by means of a methanol:aqueous acetic acid gradient elution system. The urinary molar ratios of (AAMU)/(AAMU + 1U + 1X) and (AAMU)/(1X) were estimated in 20 subjects phenotyped with dapsone, with 100% concordance for the [AAMU]/[1X] ratio. A population study of 42 unrelated individuals exhibited trimodal distribution in acetylation capacity, consistent with the Hardy-Weinberg theory of population genetics. Definitive pedigree analysis of 16 families (75 subjects) resulted in significant similarity between the observed genotypic matings and those expected by classical Mendelian segregation. This noninvasive genotyping method promises to be useful in future investigation of the relationship between the human acetylation polymorphism and clinical disorders.     

Effect of indapamide on urinary calcium excretion in patients with and without urinary stone disease

BACKGROUND: Indapamide is an antihypertensive agent similar to thiazides, but with some different effects. Thiazide and thiazide-like diuretics are useful in preventing recurrent urinary stone formation due to their hypocalciuric effects. OBJECTIVE: To determine the hypocalciuric and other effects on certain laboratory parameters of indapamide 1.5 mg in different patient groups. METHODS: Four groups of patients recruited from urology and nephrology outpatient departments were experiencing non-hypercalciuric urinary stone disease (group 1), idiopathic hypercalciuria (group 2), urinary stone disease with hypercalciuria (group 3), and essential hypertension (group 4). In all patients, fasting serum uric acid, calcium, sodium, potassium, cholesterol, triglyceride, parathyroid hormone (PTH) values, and morning second-spot urine calcium and creatinine levels were assessed before and 8 weeks after treatment with indapamide. RESULTS: Urinary calcium excretion was reduced significantly in all groups: group 1 from 0.10 +/- 0.02 to 0.07 +/- 0.03 (mean +/-SD; 30% reduction; p < 0.001), group 2 from 0.30 +/- 0.15 to 0.15 +/- 0.10 (50% reduction; p < 0.001), group 3 from 0.35 +/- 0.15 to 0.20 +/- 0.10 (43% reduction; p < 0.001), and group 4 from 0.10 +/- 0.03 to 0.08 +/- 0.02 (20% reduction; p < 0.0010). These results should be interpreted with caution since no control group was included in this study. Mean serum uric acid and triglyceride levels were significantly increased, and mean PTH and potassium levels and diastolic and systolic blood pressure were significantly decreased in all groups. Few temporary adverse effects, such as dizziness and fatigue, were noticed and none of them caused discontinuation of treatment. CONCLUSIONS: Indapamide 1.5 mg/day is effective in decreasing calciuria in patients with non-hypercalciuric urinary stone disease, idiopathic hypercalciuria, urinary stone disease with hypercalciuria, and essential hypertension. This could be achieved with few adverse effects similar to those of thiazides and indapamide 2.5 mg. Indapamide decreased the PTH levels in all groups. Long-term clinical benefits of these effects should be evaluated prospectively with further randomized studies.     

Radioimmunoassay for erythropoietin using anti-recombinant erythropoietin antibody with high affinity

A sensitive radioimmunoassay (RIA) for the detection of erythropoietin (EPO) was developed using anti-recombinant EPO antibody with high affinity. The sensitivity was 100 amol/tube (5 mIU/ml) and it was possible to detect a serum EPO level between 5 and 200 mIU/ml. This method enabled us to measure native EPO as well as recombinant EPO. With this method we determined serum EPO levels in healthy individuals and patients with chronic renal disease, rheumatoid arthritis and iron deficiency anemia. Values in patients with chronic renal disease were lower than those in healthy individuals, while values in patients with rheumatoid arthritis, or iron deficiency anemia were significantly higher than those in healthy individuals.     

Human urinary protein 1: evidence for identity with the Clara cell protein and occurrence in respiratory tract and urogenital secretions.

Protein 1 (P1), a low mol mass urinary protein of unknown function, has been purified, sequenced and quantified in human biological fluids. The molecular size, subunit composition and partial amino acid sequence of P1 are similar to those of the 10 kDa Clara cell protein (CC10), a lung secretory protein. P1 is found in high concentrations in sputum, bronchoalveolar lavages, urine and semen of healthy individuals and in urine of some pregnant women. Contrary to what is claimed, P1 or CC10 is not a specific and unique product of the lung, but like its homologue in rabbits (uteroglobulin) it is also present in urogenital secretions. P1 or CC10 may act as a natural immunosuppressor protecting the respiratory and urogenital tracts from unwanted inflammatory reactions.     

Polyphosphate binds with high affinity to exosite II of thrombin

Summary. Background: Polyphosphate (a linear polymer of inorganic phosphate) is secreted from platelet dense granules, and we recently showed that it accelerates factor V activation by thrombin. Objective: To examine the interaction of polyphosphate with thrombin. Methods and Results: Thrombin, but not prothrombin, altered the electrophoretic migration of polyphosphate in gel mobility assays. Thrombin binding to polyphosphate was influenced by ionic strength, and was evident even in plasma. Two positively charged exosites on thrombin mediate its interactions with other proteins and accessory molecules: exosite I (mainly with thrombin substrates), and exosite II (mainly with certain anionic polymers). Free thrombin, thrombin in complex with hirudin’s C‐terminal dodecapeptide and γ‐thrombin all bound polyphosphate similarly, excluding exosite I involvement. Mutations within exosite II, but not within exosite I, the Na⁺‐binding site or hydrophobic pocket, weakened thrombin binding to polyphosphate as revealed by NaCl dependence. Surface plasmon resonance demonstrated tight interaction of polyphosphate with thrombin (K_d approximately 5 nm ) but reduced interaction with a thrombin exosite II mutant. Certain glycosaminoglycans, including heparin, only partially competed with polyphosphate for binding to thrombin, and polyphosphate did not reduce heparin‐catalyzed inactivation of thrombin by antithrombin. Conclusion: Polyphosphate interacts with thrombin’s exosite II at a site that partially overlaps with, but is not identical to, the heparin‐binding site. Polyphosphate interactions with thrombin may be physiologically relevant, as the polyphosphate concentrations achievable following platelet activation are far above the approximately 5 nm K_d for the polyphosphate–thrombin interaction.     

Five methods for determining urinary calcium compared

We compared frequently used methods for calcium in urine with respect to linearity, analytical recovery, within- and between-batch imprecision, bias, and practicability. We assayed serum, lyophilized urine, native urine, and an aqueous reference solution of calcium carbonate. We found that atomic absorption spectrometry and the Corning 940 Analyzer have the widest ranges of linearity; the methylthymol blue method has the poorest analytical recovery. All methods--the aforementioned three plus the Du Pont aca and Technicon RA-1000 methods--had acceptable precision, although random errors were found with the methylthymol blue method, and, except for one type of commercial lyophilized urine assayed by the Technicon method, there were no matrix problems or difficulties with bias. We cannot recommend the methylthymol blue method, but evidently urinary calcium assays can be adequately done with many currently available methods. Intralaboratory attention to methodology should give improved performance in assessment programs.     

瑞舒伐他汀钙对急性脑梗死患者血脂和血清超敏C反应蛋白的影响

目的：比较瑞舒伐他汀钙和辛伐他汀对急性脑梗死患者血脂的疗效,并对两组患者高敏C‐反应蛋白（hs‐CRP）水平对比分析。方法选取120例脑梗死合并高脂血症的患者,随机分为观察组和对照组各60例。分别予以瑞舒伐他汀钙、辛伐他汀治疗,用药4周后检测血清脂蛋白、hs‐CRP水平。结果观察组较对照组血清低密度脂蛋白、hs‐CRP显著降低（P＜0．05）。结论瑞舒伐他汀钙可降低急性脑梗死患者的血脂及hs‐CRP水平,对急性脑梗死具有较好的疗效。     

Human epididymis protein 4 is a biomarker for transitional cell carcinoma in the urinary system

Objective: To investigate human epididymis protein 4 (HE4) levels in transitional cell carcinoma (TCC) of the urinary system and its relationship with clinicopathological features. Methods: 102 patients with TCC, 60 with benign urinary diseases, and 60 healthy controls were included in this study. The HE4 levels were used to analyze different clinicopathologic characteristics and changes between pre‐ and postsurgical operation. Results: The HE4 level was significantly increased in patients with TCC compared to patients with benign urinary diseases patients (P<0.01) and healthy controls (P<0.01), and the level of HE4 in patients with superficial TCC (Tis Ta T1) was significantly higher than that of the benign urogenital group (P<0.05)and healthy controls (P<0.05). There was a significant difference between HE4 levels in patients before and after operation (P<0.05). There was no difference between HE4 levels based on tumor recurrence, clinical TNM stage, lymph node metastasis, or pathological stage (P>0.05). The HE4 level was also different between patients with a single tumor versus patients with multiple tumors. The area under the curves of HE4 is 0.821. The sensitivity and specificity of HE4 at a cutoff value of 45.7 pM were 67.6 and 88.3%, respectively. Conclusions: HE4 may be a screening tool for early diagnosis of TCC in the urinary system, and may become a prognostic marker for TCC in the urinary system. J. Clin. Lab. Anal. 23:357–361, 2009. © 2009 Wiley‐Liss, Inc.     

Characterization and species distribution of high affinity GTP-coupled receptors for human rantes and monocyte chemoattractant protein 1

Equilibrium binding studies with recombinant human chemoattractant cytokines Rantes and monocyte chemoattractant protein 1 (MCP-1) on monocytic THP-1 cells have allowed the functional identification of two distinct receptors for C-C chemokines. One is a novel oligospecific receptor with high affinity for Rantes (50% maximal inhibitory concentration [IC50], 0.68 nM) and low affinity (IC50, 35 nM) for MCP- 1, while the other is the previously described specific receptor for MCP-1 (IC50, 0.5 nM). Receptor affinity for Rantes is enhanced on preparation of isolated membranes with a 12-fold decrease in receptor Kd. The basis of this enhancement is not understood. The Rantes receptor appears to be G protein linked, as binding activity is abolished by guanosine 5'-O-(3-thiotriphosphate) (IC50, 7.3 nM). In contrast to the consequences of MCP-1 binding, we were unable to demonstrate ligand-dependent calcium fluxes on binding of Rantes to human monocytes or THP-1 cells. The binding of Rantes and MCP-1 to mononuclear cells from dog, rabbit, and rat were tested. While high affinity binding could be demonstrated in dog and rabbit, differences in ligand-induced Ca2+ fluxes could be shown between species. This suggests that receptor-ligand interactions and receptor coupling is best examined with autologous receptors and cytokine.     

Urinary calcium response to high dose vitamin D3 with calcium supplementation in patients with multiple sclerosis

ObjectiveTo characterize the effect of vitamin D₃ intake on urinary calcium:creatinine ratios across predefined ranges of serum 25(OH)D.DesignPatients with multiple sclerosis (n = 25) received escalating doses of vitamin D₃ (4000–40,000 IU/d) with calcium (1200 mg/d).ResultsUrinary calcium:creatinine was driven by increased 25(OH)D when concentrations were < 75 nmol/L (r = 0.424, p = 0.009) and > 200 nmol/L (r = 0.281, p = 0.01), but no relationship existed when 25(OH)D concentrations were 76–200 nmol/L.ConclusionsA “safe”, physiological range of 25(OH)D concentrations is 75–200 nmol/L.     

人尿激肽原酶治疗脑梗死120例

目的:探讨人尿激肽原酶治疗脑梗死的临床疗效。方法:脑梗死患者120例,病程3h～12d。给予生理盐水100mL+人尿激肽原酶0.15PNAU静脉滴注,每日1次,连用7～14d。于治疗前后进行神经功能缺损程度评分(NIHSS),并记录不良反应。结果:人尿激肽原酶治疗脑梗死总有效率达61.7%(74/120)。120例脑梗死患者治疗前NIHSS评分为9.9±3.9,治疗7～14d后,NIHSS评分为5.5±2.8,治疗前后NIHSS评分差异有显著性(P<0.05)。<48h与48h～12d开始治疗的病例临床疗效差异无显著性。颈内动脉系统与椎基底动脉系统的脑梗死的治疗效果差异无显著性。结论:人尿激肽原酶治疗脑梗死有效且安全,在脑损害晚期仍具有促进修复和再生能力而产生神经保护作用,激肽原酶治疗脑梗死具有重要的价值。     

Dietary chloride and urinary calcium in stone disease

We studied six patients with renal stone disease, hypercalciuria,cystinuria and/or hyperuricosuria, during variations in dietaryNa and Cl intake. Switching between equimolar NaCl and NaHCO₃intakes reduced urinary Ca (UCa) during the NaHCO₃ phase, despitesteady-state urinary Na. Switching between equimolar NaCl andKCl did not change UCa, despite a sharp fall in UNa. The resultssuggest a predominant role for Cl rather than Na ions duringsodium-chloride-induced changes in UCa. In stone disease ofmixed aetiology, where alkalinization of the urine as well asreduction in UCa may be desirable, treatment with NaHCO₃ loadingis not accompanied by a rise in UCa, provided that dietary Clis maintained moderately low at 80–100 mmol/day. The mechanismwhereby Cl intake influences UCa remains undefined. Plasma PTHand calcitriol levels showed no significant alteration, andatrial natriuretic peptide levels in one patient remained unchanged.