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Magnesium is an essential trace metal and a necessary factor for multiple biochemical functions in humans. Its role in biology is fundamental in over 600 enzymatic reactions implicated in protein synthesis, mitochondrial functions, neuromuscular activity, bone formation, and immune system competence. Magnesium status is relevant in fetal development during gestation and in the newborn growth during the perinatal period. Moreover, magnesium is able to influence fetal programming and disease presentation in childhood or adulthood. The aim of this review is to focus on this metal homeostasis, analyzing its normal values, the causes of hypomagnesemia, the interaction with drugs and other conditions, and the diseases associated with magnesium value alteration during pregnancy, in order to study its role in fetal programming of adult diseases. The data here reported clearly indicated the existence of a connection between magnesium status and human pathology starting from intrauterine life and extending into childhood and adulthood. [ABSTRACT FROM AUTHOR]

The liver is a major hematopoietic organ during embryonic and fetal development in humans. Its hematopoietic activity starts during the first weeks of gestation and continues until birth. During this period the liver is colonized by undifferentiated hematopoietic stem cells (HSCs) that gradually differentiate and once mature, enter the circulatory system through the hepatic sinusoids, this process is called hepatic hematopoiesis. The morphology of hepatic hematopoiesis, has been studied in humans through the years, and led to a characterization of all the cell types that make up these phenomena. Studies on murine models also helped to describe the extent of hepatic hematopoiesis at different gestational ages. Using this knowledge, we attempted to describe how hepatic hematopoiesis morphologically evolves as gestation progresses, in human embryos and fetuses. Thus, we observed a total of 32 tissue specimens obtained from the livers of embryos and fetuses at different gestational ages. Basing our observations on the four stages of liver hematopoiesis identified by Sasaki and Sonoda in mice, we also described four consecutive stages of liver hematopoiesis in humans, which resulted to be highly similar to those described in murine models. [ABSTRACT FROM AUTHOR]

CD31 reactivity is generally utilized as a marker of endothelial cells. CD31 immunoreactivity in the developing human kidney revealed that fetal glomerular capillary endothelial cells change their immunohistochemical phenotype during maturation. The aim of this study was to analyze CD31 reactivity in the fetal human kidney in the different stages of intrauterine development: We observed different distribution of CD31-reactive vascular progenitors in the different areas of the developing kidney. In particular, the nephrogenic zone and the renal capsule were characterized by a scarcity of CD31-reactive cells at all gestational ages. These data suggest the hypothesis that nephrogenesis does not need high oxygen levels and confirms a major role of hypoxia in nephrogenesis. [ABSTRACT FROM AUTHOR]

The preterm kidney cannot be simply considered as a kidney small in size: as compared to the adult kidney, the developing organ of the preterm infant is characterized by marked differences regarding the architecture and cell components. At macroscopy, fine linear demarcations indenting the renal surface characterize the fetal and preterm kidney. At microscopy, multiple major architectural changes differentiate the developing kidney from the adult one: a large capsule with a high cellularity; the branching ureteric bud, extending from the hilum towards the renal capsule; striking morphological differences among superficial (just born) and deep (more mature) glomeruli; persistence of remnants of the metanephric mesenchyme in the hylum; incomplete differentiation of developing proximal and distal tubules. At cellular level, kidneys of preterm infants are characterized by huge amounts of stem/precursor cells showing different degrees of differentiation, admixed with mature cell types. The most striking difference between the preterm and adult kidney is represented by the abundance of stem/progenitor cells in the former. Multiple stem cell niches may be identified in the preterm kidney, including the capsule, the sub-capsular nephrogenic zone, the cap mesenchyme embracing the ureteric bud tips, the cortical and medullary interstitium, and the hilar zone in proximity of the ureteric origin. The sub-capsular area represents the major stem cell niche in the prenatal kidney. It has been defined "blue strip", due to the scarcity of cytoplasm of the undifferentiated stem/progenitors, which appear as small cells arranged in a solid pattern. All these data taken together, the morphological approach to the analysis of the preterm kidney appears completely different from that typically utilized in kidney biopsies from adult subjects. Such a different structure should be taken into account when evaluating renal function in a preterm infant in clinical practice. Moreover, a better knowledge of molecular biology of the blue strip stem/ progenitor cells could be at the basis of a new "endogenous" regenerative medicine, finalized to maintain and protect the nephrogenic potential of preterm infants till the 36th week of post-conceptional age, allowing them to escape oligonephronia and chronic kidney disease later in life. [ABSTRACT FROM AUTHOR]

With the incidence of end-stage renal disease increasing dramatically during the last ten years, its prevalence rising about 8% per year, chronic kidney disease (CKD) represents one of the most problematic public health problems worldwide. CKD represents a growing clinical problem that, in its terminal stages, requires renal replacement therapy. Kidney transplant has been proposed as the definitive therapy able to address the growing clinical, social and economic problems related to the increasing prevalence of end-stage kidney disease (ESKD). Traditional stem cell-based regenerative medicine, when applied to kidneys disrupted by end-stage renal disease, has been shown to be unable to regenerate the damaged organ. The theme of this work is to hypothesize a new approach to the prevention of CKD, based on the management of the huge amount of stem/progenitor cells physiologically present in the kidney of preterm babies at birth. Here a new concept of primary prevention of renal disease is suggested: a true primary prevention, starting in the perinatal period aimed at increasing the number of functioning glomeruli. This approach has been defined as “physiological regenerative medicine”, in order to underline the use of physiological tools, including endogenous renal stem cells and stem cell stimulators physiologically expressed in our cells. [ABSTRACT FROM AUTHOR]

Nephron number at birth has relevant clinical importance with implications for long-term renal health. In recent years, the podocyte depletion hypothesis has emerged as an important concept in kidney pathology. This study was aimed at verifying whether human podocyte number changes significantly during intrauterine life. To this end, 62 subjects with gestational ages ranging from 20 to 41 wk were examined. Kidney sections were stained with hematoxylin and eosin and digitally scanned at ×400 magnification. Subjects were subdivided into fetuses (gestational age ×24 wk, n = 5), preterms (gestational age ≥25 and ≤36 wk, n = 39), and full-term newborns (gestational age ≥37 wk, n = 18). The average podocyte number of 1,908 ± 645, 1,394 ± 498, and 1,126 ± 256 was, respectively, observed in fetuses, preterms, and full-term newborns. A significant main effect (P = 0.0051) of gestational age on podocyte number was observed with a significantly lower number in full-term newborns than in fetuses (P < 0.01). Intragroup variability was also observed. We speculate that variations in podocyte number could be correlated with factors such as drugs and maternal diet occurring during intrauterine life. In conclusion, this study shows, for the first time, a decreasing trend in podocyte number during gestation. [ABSTRACT FROM AUTHOR]

Objective. Evaluation of neuronal changes in an animal experimental model of normocapnic hypoxia- reoxygenation. Materials and Methods. Fifty male piglets were the study subjects; normocapnic hypoxia was induced in 40 piglets and ten were shamoperated (controls). When bradycardia and/or severe hypotension occurred, reoxygenation was initiated. Animals were allocated in 4 groups according to the oxygen concentration, they were resuscitated with 18%, 21%, 40%, and 100% O2. Persisting asystole despite 10 minutes of cardiopulmonary resuscitation and return of spontaneous circulation were the endpoints of the experiment. Surviving animals were euthanized and brain cortex samples were collected, hematoxylin and eosin-stained, and examined for apoptotic bodies observing 10 consecutive high power fields. Results.Histological examination of the control group did not showany pathological change. On the contrary, apoptosis of neurons was found in 87.5% of treated animals. When specimens were examined according to the oxygen concentration used for resuscitation, we found marked intergroup variability; a higher percentage of apoptotic neurons was observed in piglets of group 4 (100% oxygen) compared to the others (P = 0.001). Conclusions. This preliminary data shows that normocapnic hypoxia and reoxygenation in Landrace/Large White piglets resulted in significant histological changes in the brain cortex. The degree of pathological changes in cortical neurons was significantly associated with the oxygen concentration used for reoxygenation, with a higher percentage of apoptotic neurons being observed in piglets reoxygenated with 100% compared to 18% O2 and to 21% O2. [ABSTRACT FROM AUTHOR]

Purpose: Carotid plaques analysed by MDCTA can show contrast enhancement. The purpose of this study was to explore the association between carotid plaque enhancement (CPE) and microvessel density.Materials and Methods: We obtained IRB approval. Twenty-nine consecutive (male, 20; median age, 63) symptomatic patients studied with 16-detector CT were prospectively analysed. Examinations were performed before and after intravenous contrast medium administration, and analysis of plaque enhancement was performed. Patients underwent "en bloc" carotid endarterectomy; histological sections were prepared and the presence of microvessels quantified. Logistic regression analysis as well as ROC curve and area under the curve was calculated.Results: A statistically significant association between the degree of CPE and microvessel density (P = 0.009; rho = 0.553) was observed. The ROC curve analysis confirmed this association with an area under the curve of 0.906, 0.735, 0.644 and 0.546 for CPE of 10 HU, 15 HU, 20 HU and 25 HU respectively. There was a statistically significant difference between the CPE and the degree of neovascularisation (P = 0.0003).Conclusion: Results of this preliminary study suggest that CPE might be associated with the microvessel density. Histological analysis seems to demonstrate that the degree of intra-plaque neo-vascularisation is statistically associated with CPE.Key Points: Carotid artery plaque enhancement at CT is associated with microvessel density. The degree of intra-plaque neo-vascularisation is statistically associated with carotid plaque enhancement. Plaque enhancement at CT should be considered when assessing vulnerable plaques. [ABSTRACT FROM AUTHOR]

CD10 was first identified in tumor cells of acute lymphoblastic leukemia. Most studies on CD10 expression have dealt with tumor pathology. Since no data are available for specific role in the fetal kidney, this study aimed at investigating CD10 expression during the different phases of renal embryogenesis. To this end, the expression of CD10 was evaluated in the kidney of two human fetus and in three newborns. In both fetuses, immunostaining for CD10 was compartmentalized and mainly concentrated in the mid-deep cortex. Reactivity for CD10 was stronger in the glomerular epithelium, in proximal tubules and in metanephric mesenchymal cells. At 25 weeks of gestation, CD10 was also detected in the subcapsular regions, including some pretubular aggregates of cap mesenchymal cells and renal vesicles. At 34 weeks of gestation, we observed an increased immunoreactivity for CD10 in visceral and parietal glomerular epithelium. At 39 weeks of gestation, CD10 was also expressed in the collecting tubules and in the Henle loops. Our data show a strong expression of CD10 in all stage of human kidney development, characterized by dynamic changes and support the hypothesis that CD10 plays a relevant role in renal embryogenesis. [ABSTRACT FROM AUTHOR]

Examines subjects carrying rare variants of alpha1-antitrypsin deficiency (AATD) in Italy. Identification of alleles associated with reduced or absent plasma AAT levels; Efforts of the researchers to gain insight into the epidemiology or associated clinical phenotypes of the pathologic condition; Analysis of the genotypes carried by subjects affected by AATD.

Dermatofibrosarcoma protuberans (DFSP) is a highly recurrent low-grade soft tissue sarcoma, which is usually located on the trunk. Presentation in the vulva is rare, with only 13 cases being reported to date, none of which have been investigated at the cytogenetic or molecular level. Specific cytogenetic abnormalities, involving chromosomes 17 and 22, are characteristic features of DFSP and giant cell fibroblastoma (GCF), a tumor closely related to DFSP. These chromosomal rearrangements result in the fusion of the COL1A1 and PDGFB genes in both lesions and show wide variation in the position of the fusion point in COL1A1. Here, we describe a case of DFSP of the vulva with a typical monotonous storiform pattern, with no foci of multinucleated giant cells. Cytogenetic analysis showed a 47,XX,+r karyotype in 50% of the cells, and molecular investigation disclosed the presence of a transcript fusing COL1A1 exon 37 to PDGFB exon 2. This is the first case of DFSP showing such a fusion point, which is intriguingly identical to that found in a GCF case, indicating that the COL1A1/PDGFB fusion point position does not seem to affect tumor morphology. This finding further underlines the very close relationship between these two morphologically distinct entities. [ABSTRACT FROM AUTHOR]

A histological and ultrastructural study, coupled with transmission and scanning electron microscopy of the early changes in the liver following a single administration of cycloheximide (CHX), was carried out in male Wistar rats. At the histological level, apoptosis was already present in the liver 2 h after treatment. By scanning electron microscopy, the following sequential changes were observed: brightness and progressive detachment of hepatocytes from neighbouring cells, formation of surface infolds with multiple blebs and, finally, release of several membrane-bounded apoptotic bodies (ABs) in the extracellular space and into the sinusoidal lumen. Three hours after CHX administration, the apoptotic cycle was completed, as shown by the presence of phagocytosed ABs inside the cytoplasm of intact liver cells. Light microscopic examination of the liver 6 h after CHX administration showed ABs mainly located in the cytoplasm of intact hepatocytes and inside activated Kupffer cells. By transmission electron microscopy, it was possible to demonstrate that cells undergoing apoptosis were hepatocytes. At 24 h, the livers of treated animals appeared normal, with no evidence of apoptosis. [ABSTRACT FROM AUTHOR]

Recent observations on a correlation between fetal serum ferritin and gestational age, consistent with an increase in fetal iron stores during pregnancy, led us to study liver iron content in 22 human stillborns, newborns and infants of different gestational and postnatal age. At autopsy, a longitudinal liver slice was subdivided into ten blocks. Each sample was analyzed for iron content by atomic absorption spectroscopy. The mean iron concentration in the studied livers was 21.6 μM/g dry tissue (d.t.). A striking interindividual variability in iron content was observed: the hepatic concentration of the metal ranged from 3.3 to 64.4μM/g d.t. No correlation was found between the hepatic iron concentration and gestational age or other clinical parameters of the patients studied. Moreover, the total storage iron of the liver did not appear to be correlated with the gestational age. The analysis of iron concentration in ten blocks in each liver revealed an irregular distribution of the metal. Lobar differences were observed, with a tendency of the left lobe to accumulate more iron than the right one. Furthermore, striking differences in iron content were found between adjacent liver samples, ranging in one instance from 4.5 up to 109.0 μM/g of dry tissue. Perls' stain for iron was positive in 7 out of the 22 livers examined, showing an irregular acinar distribution, with preferential periportal localization. Our data show that the newborn liver can be considered an interesting model for the study of iron storage. The observed uneven distribution of the metal, even in the absence of fibrosis normally associated with iron storage in adults, casts doubt on the interpretation of iron concentration of a small liver sample as representative of the mean hepatic iron concentration. [ABSTRACT FROM AUTHOR]

Experiments were designed to determine the efficacy of different types of liver cell proliferative stimuli given during exposure to several liver tumor-promoting regimens, on the formation of foci of enzyme-altered hepatocytes. Male Wistar rats were initiated sith diethylnitrosamine (150 mg/kg body wt). After a 2 week recovery period animals were subjected to promoting regimens, the resistant hepatocyte model, the phenobarbital model and the orotic acid model. While the rats were on these regimens they were given liver cell proliferative stimulus, either a compensatory type (two-thirds partial hepatectomy or a necrogenic dose of carbon tetrachloride) or a direct hyperplastic stimulus such as that induced by the primary mitogen, lead nitrate. Initiated cells so promoted by these regimens were monitored as foci of enzyme-altered hepatocytes positive for γ-glutamyltransferase and placental glutathione S-transferase or deficient for adenosine triphosphatase. While carbon tetrachloride and partial hepatectomy-induced compensatory regeneration stimulated the promoting ability of the regimens used, direct hyperplasia could not stimulate the formation of foci and/or nodules from initiated hepatocytes. Evaluation of thymidine incorporation indicated that there was no significant difference in the extent of DNA synthesis in both the proliferative stimuli irrespective of the promoting procedure used. [ABSTRACT FROM PUBLISHER]

We describe the case of a Sardinian female child affected by SMARD1, a genetic composite heterozygote, in whom a new nonsense mutation (R788X) was found. A sister was affected by generalized muscular hypotonia and died from respiratory insufficiency at the age of 9 months, before a diagnostic definition had been formulated. Our patient died at 6 months due to respiratory insufficiency. At autopsy some differences with previous published cases were observed. In fact, our case is to the best of our knowledge the first report of giant cell hepatitis and myocarditis in SMARD1-affected patients, although this could be a chance association. [ABSTRACT FROM AUTHOR]

An abstract of the conference paper "Extrauterine undifferentiated endometrioid stromal sarcoma arising in endometriosis of the rectovaginal septum of a postmenopausal patient with recent onset of pelvic pain," by S. Guerriero and colleagues is presented.

The first examination of classical Kaposi's sarcoma incidence in southern Sardinia (Italy) in 1998-2002 found the highest rate recorded in the island of 2.49 per 100 000 per year (standardised). [ABSTRACT FROM AUTHOR]

The article discusses a study on two isoforms of the small proline-rich protein 3 (SPRR3) in newborn saliva. The study used different electrospray ionization-mass spectrometry (ESI-MS) approaches and c-DNA sequencing to examine the isoforms. It also showed the difference between the two proteins and one of the approximate octapeptide tandem repeats present in the isoform with higher Mav value.