Influences of angiogenesis and lymphangiogenesis on cancerous invasion in experimentally induced tongue carcinoma

BACKGROUND: Although it is clear that dissemination via the blood system involves angiogenesis, it is uncertain whether tumors also induce lymphangiogenesis or simply invade existing peritumoral vessels. The purpose of this study was to elucidate changes in tumor blood and lymph vessels in cases involving the invasion of squamous cell carcinoma in the oral cavity, and its significance. Blood and lymph vessels densities in tongue carcinomas induced in hamsters were investigated. METHODS: Tongue cancer was induced by abrading the right margin of the tongue of each hamster with an endodontic barbed broach and subsequently applying 1.0% 9,10-dimenthl-1,2-benzanthracene (DMBA) dissolved in acetone, three times a week, at the same site. Fresh frozen sections were prepared and blood vessels stained blue by perfusion with Coomassie Brilliant Blue and lymph vessels stained brown for 5'-nucleotidase. The effects on the blood vessels and lymph vessels were observed. RESULTS: The results showed that blood and lymph vessel densities were greater in the advanced carcinoma tissues than in normal tissue. These were compared in terms of the mode of cancer invasion. As tumor invasion progressed, the blood vessel density decreased but lymph vessel density tended to be higher in high-degree tumor invasion than in low-degree tumor invasion. The expression of vascular endothelial growth factor-C was seen more frequently as tumor invasion progressed. CONCLUSIONS: The present findings indicated that angiogenesis and lymphangiogenesis are affected by cancerous invasion.     

Chronic acid ingestion promotes renal stone formation in rats treated with vitamin D3

OBJECTIVE: Although hypercalciuria, a well-established adverse effect of vitamin D3, can be a risk factor of renal stone formation, the risk of nephrolithiasis has not been well defined. The consumption of a diet high in acid precursors is often cited as a risk factor for the development of calcium-based kidney stones. In the present study, we investigated the effect of chronic acid ingestion on kidney stone formation in rats treated with calcitriol (1-25[OH]2 D3). METHODS: Control rats (C-C), calcitriol-treated rats (C-V; three treatments of 0.5 microg of calcitriol per week) and acid-ingested (water containing 0.21 mol/L NH4Cl), calcitriol-treated (three treatments of 0.5 microg of calcitriol per week) rats (A-V) were fed in metabolic cages. After 1 month, urine, blood, kidney and bone samples were analyzed. RESULTS: The A-V rats exhibited elevated serum calcium concentrations, urinary calcium and phosphate excretion, urinary type I collagen cross-linked N-peptide (NTx)/creatinine values, mRNA expression of osteopontin in the kidney, and renal calcium contents as well as decreased bone mineral densities, compared with the C-C and C-V rats. Urinary citrate excretion was lower and NaDC-1 mRNA expression in the kidney was higher in the A-V rats than in the C-C and C-V rats. Calcium phosphate kidney stones were found in the A-V rats. CONCLUSIONS: The ingestion of NH4Cl, an acid precursor, promotes calcium phosphate kidney stone formation in calcitriol-treated rats. The chronic intake of a diet rich in acid precursors may be a risk factor for the development of kidney stones in subjects who are being treated with calcitriol.     

神经肽Y对心肌蛋白质合成的影响及其意义

用~3H-亮氨酸参入法与放射免疫分析法分别测定大鼠心肌蛋白质合成速度与心脏组织中神经肽Y(NPY)含量。结果显示NPY能显著促进心肌蛋白质合成,其最大效应较去甲肾上腺素(NE)大35%,所需浓度是NE的1/100。心肌梗塞后非梗塞区组织内NPY的含量在2天时无显著改变,15天时则降低71%,提示2～15天期间该区域NPY释放增加,此为非梗塞区心肌肥大的机制之一     

Minor Psychiatric Morbidity, Its Prevalence and Outcome in a Cohort of Civil Servants A Seven-year Follow-up Study

During the years 1979–1986, a cohort of direct entrantexecutive officers in the Civil Service were followed up toexamine the prevalence and outcome of minor psychiatric morbidityin an occupational setting. All studies using epidemiologicalstandardized research methods agree, that prevalence rates arehigh in occupational settings. As in primary care settings,half of the illness episodes followed a chronic course, whichemphasizes the need for early detection and prompt managementof these conditions, and for evaluative studies of interventionstrategies.     

EFFECTS OF BKCa CHANNELS ON THE REDUCTION OF CYTOSOLIC Ca2+ IN cGMP-INDUCED RELAXATION OF GUINEAPIG TRACHEA

1. In order to examine the mechanisms of cGMP-induced relaxation in airway smooth muscle, the effects of atrial natriuretic peptide (ANP) and 8-brom cGMP on muscle tone were studied by measuring isometric tension, while the effects on cytosolic Ca²⁺ concentrations were studied by measuring the spectra of fura-2 loaded in guinea-pig tracheal strips. 2. Atrial natriuretic peptide and 8-brom cGMP caused a concentration-dependent inhibition of spontaneous tone in the guinea-pig trachea. The relaxant effects of these agents on spontaneous tone were markedly suppressed in the presence of iberiotoxin (IbTX), a selective inhibitor of large-conductance Ca²⁺-activated K⁺ (BKca) channels. Iberiotoxin (30 nmol/L) markedly affected the maximal effect induced by ANP and 8-brom cGMP and augmented EC₇₀ values for ANP and EC₅₀values for 8-brom cGMP approximately 27- and 17-fold, respectively. The inhibitory effects of IbTX on relaxation induced by these agents were diminished in the presence of 1 μmol/L nifedipine, an antagonist of voltage-operated Ca²⁺channels (VOCC). 3. The inhibitory action of ANP and 8-brom cGMP on spontaneous tone was not affected by the presence of 10 μmol/L glibenclamide, an inhibitor of ATP-sensitive K⁺ channels, and 100 nmol/L apamin, an inhibitor of small-conductance Ca²+-activated K⁺ channels. When these agents were applied to tissues precontracted by high (40mmol/L) K⁺, the relaxant effects of these agents markedly diminished. 4. The extracellular Ca²⁺-dependent contraction was inhibited in the presence of 0.3 μmoI/L ANP or 0.1 mmol/L 8-brom cGMP. Concentration—response curves to extracellular Ca²⁺ (0.03—2.4 mmol/L) were markedly diminished by exposure to these agents. The maximal effect induced by extracellular Ca²⁺ was affected by these agents. 5. Atrial natriuretic peptide caused an inhibition of spontaneous tone accompanied by a reduction in the intracellular Ca²⁺ concentration. In the presence of IbTX, the elimination of both muscle tone and cytosolic Ca²⁺ by ANP was suppressed. 6. We conclude that ANP and 8-brom cGMP activate BKca channels and that the inhibition of Ca²⁺ influx through VOCC, mediated by BKca channel activation, may be involved in cGMP-dependent bronchodilation.     

心间隔缺损并哑性动脉导管未闭4例

我院治疗６６例心间隔缺损的病例中，有４例合并哑性动脉导管未闭（简称ＰＤＡ），发生率６％。全组病例术前均无ＰＤＡ临床体征，１例术前再次复查心脏彩超时发现，其余３例均漏诊。１例先处理ＰＤＡ，３例在纠正心内畸形同时处理ＰＤＡ。心间隔缺损合并哑性ＰＤＡ容易漏诊，但有其临床特点，手术可先处理ＰＤＡ，或在体外循环下处理ＰＤＡ。     

Pharmacological properties of Ca2+-activated K+ currents of ramified murine brain macrophages

Using the whole-cell configuration of the patch clamp technique, calcium-activated potassium currents (I_K,Ca) were investigated in ramified murine brain macrophages. In order to induce I_K,Ca the intracellular concentration of nominal free Ca²⁺ was adjusted to 1μM. The Ca²⁺-activated K⁺ current of brain macrophages did not show any voltage dependence at test potentials between –120 and +30mV. A tenfold change in extracellular K⁺ concentration shifted the reversal potential of I_K,Ca by 51mV. The bee venom toxin apamin applied at concentrations of up to 1μM did not affect I_K,Ca. Ca²⁺-activated K⁺ currents of ramified brain macrophages were highly sensitive to extracellularly applied charybdotoxin (CTX). The half-maximal effective concentration of CTX was calculated to be 4.3nM. In contrast to CTX, the scorpion toxin kaliotoxin did not inhibit I_K,Ca at concentrations between 1 and 50nM. Tetraethylammonium (TEA) blocked 8.0% of I_K,Ca at a concentration of 1mM, whereas 31.4% of current was blocked by 10mM TEA. Several inorganic polyvalent cations were tested at a concentration of 2mM for their ability to block I_K,Ca. La³⁺ reduced I_K,Ca by 72.8%, whereas Cd²⁺ decreased I_K,Ca by 17.4%; in contrast, Ni²⁺ did not have any effect on I_K,Ca. Ba²⁺ applied at a concentration of 1mM reduced I_K,Ca voltage-dependently at hyperpolarizing potentials. Received: 17 January / Accepted: 5 May 1997     

硒和/或维生素E预防大鼠内皮细胞损伤的实验研究

用含硒（Ｓｅ０．５ｍｇ／ｋｇ）和／或维生素Ｅ（ＶＥ０．６ｇ／ｋｇ）的高脂饲料喂养成年雄性Ｗｉｓｔａｒ大鼠１２周。结果：高脂对照组大鼠血浆前列腺素Ｆｌα（６－酮－ＰＧＦ１α）水平下降，而血清脂质过氧化物（ＬＰＯ）、血浆血栓素（ＴＸＢ２）及内皮素（ＥＴ）水平上升；补Ｓｅ、ＶＥ及Ｓｅ＋ＶＥ可明显降低大鼠血清ＬＰＯ、血浆ＴＸＢ２、ＥＴ及ＴＸＢ２／６－酮－ＰＧＦ１α比值。同时，除了明显提高血浆谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）活力外，血浆６－酮－ＰＧＦ１α浓度明显升高。实验提示，Ｓｅ和／或ＶＥ有调节花生四烯酸代谢及保护内皮细胞的作用。     

补肾中药对肾虚骨质疏松症大鼠红细胞膜PKC、 Ca2+-Mg2+- ATP酶活性影响的实验研究

本实验研究切除卵巢造成肾虚骨质疏松症大鼠模型。通过观测红细胞膜蛋白激酶Ｃ（ＰＫＣ）和Ｃａ２＋－Ｍｇ２＿－ＡＴＰ酶的活性，探讨肾虎骨质疏松症病理机制中肌醇脂质系统的变化，并结合全身和脊柱骨密度（ＢＭＤ）指标观察了补肾中药（密骨灵）的疗效，与正常对照组、模型空白组和阳性药（骨疏康颗粒剂）对照组进行对照，探讨补肾法的防治机理。结果表明；模型空白组大鼠红细胞膜ＰＫＣ和Ｃａ２＋－Ｍｇ２＋－ＡＴＰ酶、Ｍｇ２＋－ＡＴＰ酶的活性明显低于正常组（ｐ均＜０．０５）；密骨灵组与骨疏康组大鼠全身、脊柱ＢＭＤ和红细胞膜ＰＫＣ、Ｃａ２＋－Ｍｇ２＋－ＡＴＰ酶的活性均明显高于模型空白组（ｐ均＜０．０５），并且与正常组大鼠无明显差别（ｐ均＞０．０５）；密骨灵组大鼠红细胞膜Ｍｇ２＋－ＡＴＰ酶活性高于模型空白组和骨疏康组（ｐ＜０．０５），并且与正常组无显著性差异（ｐ＞０．０５）；密骨灵组大鼠红细胞膜ＰＫＣ活性高于骨疏康组（Ｐ＜０．０５）。结论：肾虎骨质疏松症具有红细胞膜ＰＫＣ和Ｃａ２＋－Ｍｇ２＋－ＡＴＰ酶、Ｍｇ２＋－ＡＴＰ酶活性的改变；密骨灵可以恢复肾虎骨质疏松症大鼠全身骨量，达到防治目的；补肾中药可以恢复红细胞膜ＰＫＣ活性和钙镁泵的活性，是补     

Study of the role of vitamin B12 and folinic acid supplementation in preventing hematologic toxicity of zidovudine

Abstract: A prospective, randomized study was conducted to evaluate the role of vitamin B₁₂ and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4 + cell counts < 500/mm³ were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B₁₂ (1000 μg monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B₁₂ and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm³ and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B₁₂ or folate levels and development of myelosuppression. Vitamin B₁₂ and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.