The human placenta: a model for tenascin expression

Summary Tenascin is a large glycoprotein of the extracellular matrix. Previous reports have demonstrated that it is associated with epithelial-mesenchymal interfaces and is expressed during embryonic and tumour development, wound healing, cell proliferation and it may be involved in immunomodulation. The human placenta shows numerous features related to these aspects. We have investigated the presence of tenascin in the human placenta throughout pregnancy by immunohistochemistry. We used monoclonal (mAb) and polyclonal (pAb) antibodies to tenascin, a mAb to fibrin, a pAb to fibrinogen, and the mAb Ki-67 as proliferation marker. Tenascin was highly expressed in the mesenchymal villi which are considered the basis of growth and differentiation of the villous trees. Moreover, fibrinoid deposits at the surfaces of the villous trees were always separated from the fetal stroma by tenascin. The stroma of villi encased in fibrinoid was also positive for tenascin. This glycoprotein was also expressed in the villous stroma directly apposed to cell islands and cell columns. In the proximal portions of both epithelial structures, cytotrophoblast was Ki-67 positive. These data show that tenascin is expressed during the development of the placenta, particularly in the mesenchymal villi, cell islands and cell columns. These structures are considered to be the proliferating units of the villous trees. Tenascin underlying fibrinoid deposits suggests that it also participates in repair mechanisms. Thus, in the human placenta tenascin expression can be correlated with villous growth, cell proliferation, and fibrinoid deposition. Its role in immunoprotection of fetal tissues in areas where syncytiotrophoblast as barrier is missing or damaged is discussed.     

The human placenta: a model for tenascin expression.

Tenascin is a large glycoprotein of the extracellular matrix. Previous reports have demonstrated that it is associated with epithelial-mesenchymal interfaces and is expressed during embryonic and tumour development, wound healing, cell proliferation and it may be involved in immunomodulation. The human placenta shows numerous features related to these aspects. We have investigated the presence of tenascin in the human placenta throughout pregnancy by immunohistochemistry. We used monoclonal (mAb) and polyclonal (pAb) antibodies to tenascin, a mAb to fibrin, a pAb to fibrinogen, and the mAb Ki-67 as proliferation marker. Tenascin was highly expressed in the mesenchymal villi which are considered the basis of growth and differentiation of the villous trees. Moreover, fibrinoid deposits at the surfaces of the villous trees were always separated from the fetal stroma by tenascin. The stroma of villi encased in fibrinoid was also positive for tenascin. This glycoprotein was also expressed in the villous stroma directly apposed to cell islands and cell columns. In the proximal portions of both epithelial structures, cytotrophoblast was Ki-67 positive. These data show that tenascin is expressed during the development of the placenta, particularly in the mesenchymal villi, cell islands and cell columns. These structures are considered to be the proliferating units of the villous trees. Tenascin underlying fibrinoid deposits suggests that it also participates in repair mechanisms. Thus, in the human placenta tenascin expression can be correlated with villous growth, cell proliferation, and fibrinoid deposition. Its role in immunoprotection of fetal tissues in areas where syncytiotrophoblast as barrier is missing or damaged is discussed.     

Placental structure in gestational diabetes mellitus

The placenta is a transitory organ, located between the mother and the foetus, which supports intrauterine life. This organ has nutritional, endocrine and immunologic functions to support foetal development. Several factors are related to the correct functioning of the placenta including foetal and maternal blood flow, appropriate nutrients, expression and function of receptors and transporters, and the morphology of the placenta itself. Placental morphology is crucial for understanding the pathophysiology of the organ as represents the physical structure where nutrient exchange occurs. In pathologies of pregnancy such as diabetes mellitus in humans and animal models, several changes in the placental morphology occur, related mainly with placental size, hypervascularization, higher branching capillaries of the villi and increased glycogen deposits among others. Gestational diabetes mellitus is associated with modifications in the structure of the human placenta including changes in the surface area and volume, as well as histological changes including an increased volume of intervillous space and terminal villi, syncytiotrophoblast number, fibrinoid areas, and glycogen deposits. These modifications may result in functional changes in this organ thus limiting the wellbeing of the developing foetus. This review gives an overview of recurrent morphological changes at macroscopic and histological levels seen in the placenta from gestational diabetes in humans and animal models. This article is part of a Special Issue entitled: Membrane Transporters and Receptors in Pregnancy Metabolic Complications edited by Luis Sobrevia.     

Influence of volume expansion on sodium excretion during parabiotic dialysis.

Dialysis of a saline-infused against a noninfused dog was associated with a significant increase in Na excretion in both animals without a significant change in creatinine clearance or filtered Na. This indicates that there was movement by diffusion of a humoral agent between the two animals. The observed increase in Na excretion in the noninfused animal resulted from gain of a natriuretic hormone, since in a second series of experiments a natriuretic rather than antinatriuretic hormone appeared to be involved.     

Recent environmental toxic effect in the Polish copper mining territory on human reproduction. Part I. Response of the placenta to the chemical stress

This study examined morphochemical differences between 49 full term human placentas collected from healthy non-smoking women living in the high polluted region, i.e. the Copper Mining Territory (CMT) and the 38 control placentas (C) obtained from little polluted eastern Carpathian regions. The placentas were studied by histochemical, immunohistochemical and morphometric methods. In CMT placentas a decrease in the cytochrome c oxidase and glucose-6-phosphate activities and the immunoreactivity of glutathione S-transferase pi in the villous syncytiotrophoblast and amniotic epithelium was noted. All CMT placentas showed abundance of mineral and fibrinoid deposits and of lipid droplets. This produced a compensatory increase in the mother-fetus exchange area due to excessive proliferation of placental villi which in turn decreased the intervillous space and thus the influx of indispensable maternal blood. Lately slight signs of increase in the cytochrome c oxidase activity accompanied by a noticeable decrease in number of the thinnest (most abundant) terminal villi is observed.     

Creatinine and inulin clearance at the different nitrogen and energy intake in sheep

1. Renal creatinine and inulin clearances were compared between sheep fed (a) high nitrogen and high energy diet; (b) low nitrogen and high energy diet and (c) low nitrogen and low energy diet. 2. Inulin clearance was significantly lower in sheep on both low nitrogen diets vs the group with high nitrogen intake. Differences were not ascertained between the groups on low nitrogen diets. 3. No significant differences were found in the creatinine clearance. The creatinine inulin clearance ratio was higher when animals were fed low nitrogen diets, vs the group on a high nitrogen diet. 4. Results suggest that the endogenous creatinine is not suitable for the GFR measurement in sheep under the different conditions of nutrition.     

Renal function after long-term treatment with lithium.

Daily urine volumes, plasma creatinine concentrations, and creatinine clearance were measured in 106 patients with unipolar and bipolar affective disorders attending a "lithium" clinic. Urine volumes exceeded 3.51 in only six patients, plasma creatinine concentrations exceeded 150 mumol/1 (1.7 mg/100 ml) in only five, and creatinine clearance was below 50 ml/min in 16. Renal function was assessed by measuring creatinine clearance and renal tubular function, including response to 20 hours of water deprivation, in a representative sample of 30 patients from the lithium clinic and 30 psychiatric patients matched for age and sex who were taking other psychotropic drugs. Creatinine clearance and tubular function, including urine osmolality after water deprivation, were not significantly different between the two groups. Urinary excretion of arginine vasopressin (AVP), however, was much greater in the lithium-treated patients, who therefore had a diminished tubular responsiveness to AVP. The findings do not support suggestions that long-term lithium treatment results in seriously impaired renal function, renal damage, and polyuria. Compared with other series, however, the patients were being maintained with low serum lithium concentrations, which apparently area as effective prophylactically as higher concentrations.     

Effects of gender on kidney function in magnesium-deficient rats

This study investigated the gender differences in the kidney function of magnesium (Mg)-deficient rats. Male and female rats were fed a control diet or a Mg-deficient diet for 21 d. Mg-deficient diet had no significant effect on kidney calcium (Ca) or phosphorus (P) concentration in male rats, while Ca and P concentrations in female rats were significantly higher in Mg-deficient rats than in the control rats. With regard to indicators of kidney function, no significant differences in creatinine clearance and serum urea nitrogen concentration were observed among the groups. Serum albumin concentrations were significantly lower in rats fed the Mg-deficient diet than in rats fed the control diet. In both sexes, urinary albumin excretion was significantly higher in rats fed the Mg-deficient diet than in rats fed the control diet. Gender differences had no significant influence on creatinine clearance, serum urea nitrogen concentration, serum albumin concentration and urinary albumin excretion. These results suggest that gender differences have no effect on kidney function in Mg-deficient rats under the condition used.     

The effect of atrial natriuretic peptide on acid-base balance in rats with chronic renal failure

We explored the effects of 12-hour infusion of atrial natriuretic peptide (alpha-rANP:rat, 1-28) on arterial acid-base balance, using 5/6 nephrectomized rats with chronic renal failure. Before the infusion, nephrectomized rats had a higher mean arterial blood pressure, greater urine volume, and lower creatinine clearance than the normal controls, but they did not show a significant difference in arterial hydrogen ion concentration (pH), plasma bicarbonate concentration (HCO3-), partial pressure of carbon dioxide (PCO2), plasma base excess (BE), or plasma ANP concentration. alpha-rANP infusion produced a continuous blood pressure reduction in both nephrectomized and control rats. Urine volume and urinary sodium and potassium excretion tended to increase at 2-hour infusion, but not at 12-hour infusion. In the controls alpha-rANP significantly increased pH from 7.47 to 7.50, and decreased PCO2 by 14%. In contrast, in nephrectomized rats alpha-rANP significantly decreased pH from 7.48 to 7.44, HCO3- by 13%, and BE from -0.07 to -3.22 meq/l. Rats with chronic renal failure had greater reduction in HCO3- than the controls (p less than 0.05). There was no difference in plasma ANP level between the two groups. Thus, it is indicated that the long-term infusion of alpha-rANP reduces pH in rats with chronic renal failure, thereby adversely affecting the acid-base balance.     

Stereological analysis of alpha and beta zones of syncytiotrophoblast in human term placenta.

The investigations were carried out to attempt to define and analyze various quantitative structural parameters of syncytiotrophoblast in human term placenta, especially of its functionally active parts, that is alpha and beta zones. The results demonstrated the following: The arrangement of alpha and beta zones in the placenta as a whole is even and regionally independent. Beta zones prevail quantitatively. Alpha zones make up only 8% of the total volume, 18% of the total surface and 39% of the thickness of beta zones. Sexual dimorphism is shown by a significantly higher volume density (VVa)(P less than 0.002), total volume (Va)(P less than 0.05) and surface density (SVa) (P less than 0.025) of alpha zones in placentas of female newborns. The fetoplacental index is higher in male newborns. During the tenth lunar month the structure of syncytiotrophoblast is changed. Between the 38th and 39th week the volume and surface densities of alpha zones are significantly higher (P less than 0.01), and in the 40th week the volume density and total volume of beta zones prevail significantly (P less than 0.01).     

前列地尔联合尿毒清颗粒对慢性肾衰竭患者血清甲状旁腺激素、同型半胱氨酸水平及临床疗效的影响

目的:探究前列地尔联合尿毒清颗粒对慢性肾衰竭患者血清甲状旁腺激素、同型半胱氨酸及临床疗效的影响。方法:收集我院收治的慢性肾衰竭患者74例,根据随机对照表分为对照组和试验组,每组37例。对照组予以前列地尔注射液治疗,试验组在对照组基础上予以尿毒清颗粒治疗。观察并比较两组患者临床疗效,治疗前后血清肌酐(SCr)、尿素氮(BUN)、血尿酸(UA)、内生肌酐清除率(Ccr)、超敏C反应蛋白(hs-CRP)、同型半胱氨酸(Hcy)、甲状旁腺素(PTH)、β2微球蛋白(β2-MG)水平以及不良反应的发生情况。结果:与对照组相比,试验组治疗后临床总有效率较高(P0.05)。两组治疗后血清肌酐、尿素氮、血尿酸水平下降(P0.05),内生肌酐清除率水平升高(P0.05);与对照组相比,试验组血清肌酐、尿素氮、血尿酸水平较低(P0.05),内生肌酐清除率水平较高(P0.05)。两组治疗后超敏C反应蛋白、同型半胱氨酸、甲状旁腺素以及β2微球蛋白水平降低(P0.05);与对照组相比,试验组超敏C反应蛋白、同型半胱氨酸、甲状旁腺素以及β2微球蛋白水平较低(P0.05)。两组不良反应发生情况相比差异无统计学意义(P0.05)。结论:前列地尔联合尿毒清颗粒对慢性肾衰竭患者的临床疗效显著,安全性较高,可能与其下调血清甲状旁腺激素以、同型半胱氨酸及β2微球蛋白水平有关。     

孤立肾多发结石患者超声引导微创经皮肾穿刺取石术治疗的效果分析

目的:分析孤立肾多发结石患者超声引导微创经皮肾穿刺取石术治疗的效果。方法:64例孤立肾多发结石患者随机均分为试验组和对照组。其中对照组患者均采用常规开放式取石术治疗,试验组患者则在超声引导下实施微创经皮肾穿刺取石术治疗。比较两组患者的手术时间和术中出血量以及术后取净率等临床资料。结果:两组患者的手术时间并无明显差异(t=1.942,P0.05)且试验组患者的术后取净率和术后两个月排净率均显著高于对照组患者(t=4.731,P0.05,t=4.288,P0.05);对照组患者的并发症发生率显著高于试验组患者(t=4.333,P0.05);试验组患者的术中出血量显著低于对照组(t=3.762,P0.01)。两组患者术前术后以及术后2个月的血肌酐水平比较均无明显差异(均P0.05),并且两组患者血肌酐水平组间比较亦无明显差异(均P0.05)。结论:超声引导下对孤立肾多发结石患者实施微创经皮肾穿刺取石术治疗具有较高的安全性和临床疗效。     

化疗联合冷循环射频消融术治疗原发性肝癌的效果分析

目的：探讨化疗联合冷循环射频消融术治疗原发性肝癌的疗效及安全性。方法：108例原发性肝癌患者随机分为两组,均给予灌注化疗,每4周进行一次灌注化疗,对照组（n=54）进行3次,治疗组（n=54）只进行一次。治疗组给予冷循环射频消融术。评价生活质量Kamofsky评分,治疗前后检查患者的血、尿、便常规,肝肾功能（包括天冬氨酸转氨酶、丙氨酸转氨酶（AVr）、白蛋白（ALB）、总胆红素、肌酐及尿素氮等指标）,甲胎蛋白（AFP）,T细胞亚群和加强肝脏CT扫描。随访1年,经CT确定肝癌复发。结果：治疗组Kamofsky评分有效率为59．26％,对照组Kamofsky评分有效率为37．03％,两组Kamofsky评分有效率相比较,差异有统计学意义（P〈0．05）。两组治疗后症状变化相比较,除腹胀外其余各项指标差异均有统计学意义（P〈O．05）。治疗后两组相比较,ALT和AFP差异有统计学意义（P〈0．05）。治疗后两组T细胞亚群变化相比较,治疗组各项指标均变化显著（P〈0．05）。治疗后随访一年,治疗组复发率为22．22％;对照组复发率为53．70％。两组治疗一年后复发率相比较,差异有统计学意义（P〈0．05）。结论：化疗结合冷循环射频消融术治疗原发性肝癌疗效肯定,并发症及副作用小,复发率低。     

Bone fracture in elderly female with primary hyperparathyroidism: relationship among renal function, vitamin D status and fracture risk

Among 12 aged postmenopausal females with primary hyperparathyroidism, 5 had no bone fracture and 7 had fractures. Both serum 1,25 (OH)2D levels and creatinine clearance values in patients with fracture were significantly lower than those without fracture (p less than 0.025). In addition, significant positive correlation was observed between serum 1,25 (OH)2D levels and creatinine clearance values (p less than 0.05). These data suggest that decreased serum 1,25 (OH)2D level due to renal dysfunction may causally correlate to bone fracture in postmenopausal primary hyperparathyroidism.     

The relationship between adiponectin, ageing and renal function in a bi-ethnic sample

Ageing is associated with elevated adiponectin levels. Our aim was to assess whether age-related increase in adiponectin is associated with a decrease in renal function. The study comprised African (N=277) and Caucasian (N=326) men and women. Adiponectin levels, estimated creatinine clearance rate and obesity indices were determined. African men revealed significantly higher adiponectin levels compared to Caucasian men (p<0.01), reflecting the lower adiposity levels of the African men. No difference in obesity measures (p=0.92) and adiponectin levels (p=0.27) was observed between African and Caucasian women. A significant increase in adiponectin levels with ageing was observed in both African men and women (p<0.01). To the contrary, progressive ageing seems not to be significantly related to elevated adiponectin levels within Caucasians. Renal impairment decreased significantly within all of the groups (p<0.01). Single regression analyses performed in all specified groups revealed significant associations between adiponectin and estimated creatinine clearance, however a multiple regression model revealed that insulin resistance had the strongest association with adiponectin within all the groups. In conclusion, age-related rise in adiponectin levels observed in Africans may not be due to renal impairment.     

Effect of rosmarinic acid on inhibition of gentamicin induced nephrotoxicity in rats

The present investigation reports the effect of rosmarinic acid (RA), an antioxidant on gentamicin sulphate (GS)-induced renal oxidative damage in rats. Rosmarinic acid (RA) has been demonstrated to have antioxidant, free radical scavenger and anti-inflamatory effects. Twenty-eight Sprague-Dawley rats were divided in to four equal groups as follows: group 1 (control), group 2 (GS 100 mg/kg/d ip), group 3 (GS 100 mg/kg/d ip + RA 50 mg/kg/d) and group 4 (GS 100 mg/kg/d ip + RA 100 mg/kg/d). Treatments were administrated once daily for 12 days. After 12 days 24 h urine was collected, blood was sampled and kidneys were removed. Serum and kidney tissue MDA assessed by thiobarbituric acid. Kidney paraffin sections (5 μm thickness) from the left kidney stained with periodic acid Schiff. Tubular necrosis was studied semiquantitatively and glomerular volume and volume density of proximal convoluted tubule (PCT) estimated stereologically. Kidney homogenize were prepared from right kidney. Serum creatinine, urea and kidney antioxidant enzymes activity were assessed by special kits. Data were compared by SPSS 13 software and Mann–Whitney test at p < 0.05. Co treatment of GS and RA (High dose) significantly decreased serum creatinine, MDA, urea, tubular necrosis (p < 0.05) and increase renal GSH, GPX, CAT, SOD, volume density of PCT and creatinine clearance significantly in comparison with GS group (p < 0.05). Treatment with RA (high dose) maintained serum creatinine, volume density of PCT, renal GSH, GPX, SOD and MDA as the same level as control group significantly (p < 0.05). In conclusion, RA alleviates GS nephrotoxicity via antioxidant activity, increase of renal GSH content and increase of renal antioxidant enzymes activity.     

Metabolic syndrome during gestation and lactation: An important renal problem in dams. selenium renal clearance

BackgroundMetabolic syndrome (MS) in lactating dams leads to several cardiometabolic changes related to selenium (Se) status and selenoproteins expression which produce hypertension. However, little is known about the state of these dams’ kidney functions and their Se deposits.MethodsTwo experimental groups of dam rats were used: control (Se: 0.1 ppm) and MS (Fructose 65 % and Se: 0.1 ppm). At the end of lactation (21d postpartum) kidney weight and protein content, Se deposits, and the activity of the antioxidant selenoprotein glutathione peroxidase (GPx) were measured in dams. Kidney functional parameters: albuminuria, creatinine clearance, serum aldosterone and uric acid levels and water and electrolyte (Na⁺ and K⁺) balance were also evaluated. Systolic blood pressure (SBP) was measured.ResultsIn MS dams at the end of lactation Se deposits and GPx activity are higher in the kidney; however, lipid renal peroxidation appears, relative Se clearance increases, and the dams have lost Se by urine. MS dams have polyuria and polydipsia, high uric acid serum levels, albuminuria and high creatinine clearance, implying glomerular renal malfunction with protein loss. They also present hypernatremia, hypokalemia and hyperaldosteronemia, leading to high SBP; however, a natriuretic process is taking place.ConclusionSince these alterations appear, at least in part, to be related to oxidative stress in renal cells, Se supplementation could be beneficial to avoiding greater lipid renal oxidation during lactation.     

Kidney adaptation in nitric oxide-deficient Wistar and spontaneously hypertensive rats

We investigated the renal structural and functional consequences of nitric oxide (NO) deficiency co-treated with angiotensin-converting enzyme inhibitor (ACEi) in 20 adult male Wistar rats and 20 spontaneously hypertensive rats (SHR). The animals were separated into eight groups (n = 5) and treated for 30 days: Control, L-NAME (NO deficient group), Enalapril, L-NAME + Enalapril. The elevated blood pressure in NO deficient rats was partially reduced by enalapril. Serum creatinine was elevated in L-NAME-SHRs and effectively treated with enalapril. The proteinuria was significantly higher only in L-NAME-SHRs, and this was reduced by treatment with ACEi. The glomerular volume density (Vv(gl)) in L-NAME rats, both Wistar and SHR, was greater than in matched control rats, and enalapril treatment effectively prevented this Vv(gl) increase. No significant differences were observed in tubular volume density, Vv(tub), or tubular surface density, Sv(tub), in all Wistar groups. The Vv(tub) was smaller in L-NAME-SHRs than in control SHRs, and this tubular alteration was not prevented by enalapril. The Sv(tub) was not different among the SHR groups. In Wistar rats no changes were seen in vascular surface density, but a greatly increased cortical vascular volume density was seen in the enalapril treated rats. The vascular length density was greatly diminished in NO deficient rats that was effectively prevented with enalapril treatment. The vascular cortical renal stereological indices are normally reduced in SHRs. Administration of enalapril, but not L-NAME, changed this tendency. However, enalapril was not totally effective in preventing vascular damage in SHR NO deficient animals.     

Cyclosporin treatment of IgA nephropathy: a short term controlled trial.

Cyclosporin''s known regulatory effects on the immune system suggest that it may be useful in treating patients with IgA nephropathy. A randomised prospective single blind study of 19 patients with IgA nephropathy and proteinuria (greater than 1.5 g/day) was conducted to determine the therapeutic value of cyclosporin. The patients were divided into two groups: nine patients were given oral cyclosporin (5 mg/kg/day) for 12 weeks and 10 patients a placebo. The two groups were comparable in age of presentation, ratio of men to women, plasma creatinine and serum IgA concentrations, creatinine clearance, daily urinary protein excretion, severity of renal histopathological changes, and prevalence of hypertension. A significant reduction of proteinuria and an increase of plasma albumin concentration was observed with treatment with cyclosporin. Nevertheless, a significant rise of plasma creatinine concentration and a fall in creatinine clearance was found in patients after six weeks'' treatment with cyclosporin, although the plasma cyclosporin concentrations were maintained within a narrow therapeutic range. Serum IgA concentrations were reduced in seven patients. Renal function improved within eight weeks after treatment was stopped. Three months after treatment was stopped proteinuria remained less than half of the pretreatment values in three patients. No similar biochemical changes were observed in the controls. Short term cyclosporin therapy may be beneficial in reducing proteinuria in some patients with IgA nephropathy. As transient renal impairment was seen, despite cyclosporin concentrations being maintained within a narrow therapeutic range, indiscriminate use of cyclosporin in glomerulonephritis should be discouraged.     

Localization of intermediate filament proteins in various structures of the human placenta as revealed by immunoperoxidase technique.

Formalin-fixed, paraffin embedded fragments of normal human placenta were subjected to immunoperoxidase technique with the use of Dako Kits appropriate for detection of vimentin, desmin, and cytokeratins (K 660, 530, and 518 respectively). Distribution of the intermediate filament proteins in syncytiotrophoblast, connective tissue of villous stroma, walls of blood vessels as well as in cells of basal plate and placental islets was compared. General pattern of staining and its localization was characteristic for each of the 3 types of antibodies. In spite of that, most structures observed revealed the presence of more than one type of intermediate filament proteins, with the exception of syncytiotrophoblast containing cytokeratins only. Staining of blood serum and of connective tissue matrix with anti-desmin and anti-cytokeratin antibodies was also observed, whereas fibrinoid remained always negative.