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Biomedical subjects

M De Falco

Publications and source records attributed to M De Falco.

At least 19 recordsLinked to original sources
PubMed2007

Modulation of apelin and APJ receptor in normal and preeclampsia-complicated placentas.

Apelin is an endogenous ligand of the human orphan receptor APJ. This peptide is produced through processing from the C-terminal portion in the pre-pro-protein consisting of 77 amino acid residues and exists in multiple molecular forms. Although the main physiological functions of apelin have not yet been clarified, it is known that apelin is involved in the regulation of blood pressure, blood flow and central control of body fluid homeostasis in different organs. Since human placenta is a tissue where vasculogenesis, blood pressure and flow are dramatically important to allow a normal embryonic and fetal growth and development, the aim of the present study was to investigate the immunohistochemical distribution of apelin and APJ in normal placentas throughout pregnancy and in preeclampsia-complicated placentas. Specifically, we observed that in normal placentas the expression levels of apelin decreased from the first to the third trimester of gestation in both cytotrophoblast and syncytiotrophoblast cells and in the stroma of placental villi, in contrast with increased expression levels of APJ in the cytoplasm of cytotrophoblast cells and in the cytoplasm of endothelial cells of normal placenta samples. In contrast, in preeclampsia-complicated pregnancies, we observed a very strong increase of expression levels of both apelin and APJ receptor in all the placental compartments, cytotrophoblast, syncytiotrophoblast and stroma with a particular increase in endothelial cells inside preeclamptic placental villi. Our data seem to indicate an important role of apelin and APJ in the regulation of fetal development through a correct regulation of human placenta formation during pregnancy. Moreover, the strong expression levels of apelin and APJ in preeclamptic placentas, suggest their possible involvement in the onset of this pathology.

Adult↗
PubMed2006

[GnRH agonists and antagonists in the preoperative therapy of uterine fibroids: literature review].

Uterine leiomyomas are the most frequent gynecological benign tumors. Their growth is regulated by ovarian steroids, therefore a hypoestrogenic state, like menopause or pharmacologically induced pseudo-menopause by GnRH-agonists or GnRH-antagonists, is associated with the decrease of their volume. This volume reduction allows a less invasive surgical procedure and may reduce the amount of blood loss during surgery. Therefore, GnRH-agonists and antagonists are used in presurgical treatment of uterine fibromatosis. This review analyses the effects of GnRH-agonists and GnRH-antagonists therapies. GnRH-agonists produce a down-regulation of GnRH receptor, while GnRH-antagonists compete with endogenous GnRH for pituitary binding sites. Due to the lack of any intrinsic activity of GnRH-antagonists, the characteristic initial flare-up observed with GnRH-agonist treatment is absent. So, GnRH-antagonists rapidly suppress gonadotropin release within 4-8 h, while GnRH-agonists show clinical effects after 2 or 3 weeks of treatment. GnRH-antagonist activity is dose-dependent so it is possible to adjust the dose to obtain the proper levels of inhibition. The GnRH-agonist presurgical treatment usually is a short-term therapy (3-6 months), because it causes side-effects like menopause symptoms. GnRH-antagonist clinical effects can be achieved with a short-time therapy too. Their side-effects include flushes and head-ache. After stopping therapy with both drugs, leiomyomas rapidly achieve their original size while side-effects disappear. Further studies are necessary to establish the use of GnRH-antagonists in leiomyomas therapy, but in Italy this is not possible because their use is not approved.

Female↗
PubMed2005

Apoptosis and human placenta: expression of proteins belonging to different apoptotic pathways during pregnancy.

Apoptosis occurs during normal development and it is important for the right balance between the loss of old, non-functional cells and the formation of new cells in different organs and tissues. Apoptosis is triggered by different cell-type-specific signals which involve several pathways, such as mitochondrial and receptor-mediated pathways, resulting in caspase cascade activation. Several studies have suggested that apoptosis plays an important role in the normal development, remodelling and aging of the placenta. Moreover, it has been demonstrated that apoptosis increases as pregnancy progresses suggesting that it is a normal physiological phenomenon throughout gestation. In the last years, it has been hypothesized that the process known as syncytial fusion is directly or indirectly related to apoptotic events. In particular, it has been suggested that cytotrophoblast cells early express most important apoptotic proteins that translocate in the syncytiotrophoblast with the fusion. This suggests that apoptosis has a central role in the villous trophoblast turnover. Recently, another important involvement of apoptotic processes in human placenta has been demonstrated. In particular, the apoptosis, mainly through Fas-FasL or TRAIL-R-TRAIL signalling, may be a defence mechanism against rejection of the fetal allograft by maternal immune system. The whole data suggest that regulation of apoptotic events is important to allow a correct development, differentiation and function of the placenta throughout pregnancy and that an unbalance of this process leads to severe pathologies such as pre-eclampsia and intrauterine growth retardation. Therefore, due to its extensive proliferation and invasive properties, the placenta mimics a malignant tumor and represents an interesting model to evaluate those processes leading to carcinogenesis.

Animals↗
PubMed2005

Helicobacter pylori and gastric epithelial cells: from gastritis to cancer.

Helicobacter pylori is a spiral, gram-negative rod-shaped pathogen that attaches to gastric epithelial cells in the human stomach and is a causative agent of chronic active gastritis, peptic ulcer and neoplasia. H. pylori is one of the most common pathogens afflicting humans and is the major environmental factor in the development of gastric cancer increasing from 4 to 6 folds the risk of its development. Several specific virulence factors are implicated in the mechanism of H. pylori infection like the bacterial motility; the secretion of large amounts of urease; specific adhesins for the interaction between H. pylori and the gastric surface epithelium; the traslocation into gastric ephitelial cells of the cytotoxin-associated gene A (CagA), the vacuolating cytotoxin A (VacA) and the heat shock protein HspB. Adherence of H. pylori to the gastric epithelium and secretion of interleukins are believed to be an important step in the induction of active inflammation of the mucosal layer. Several studies have demonstrated that H. pylori infection induces gastric epithelial cell proliferation activating ERK and MAPK pathways and increase of mitosis and mutations. Therefore, H. pylori infection seems to increase apoptosis, implying increased gastric epithelial cell turnover. Recently, it has been shown that H. pylori-induced apoptosis in gastric epithelial cells is mediated via the CD95-receptor/ ligand system but that TRAIL also plays an important role in this regulation.

Gastric Mucosa↗
PubMed2005

Major complications in thyroid surgery: utility of bipolar vessel sealing (Ligasure Precise).

In the present study the Authors tried and assess the advantages of the standard sutureless thyroidectomy performed by the Ligasure Vessel Sealing System, thanks to the use of the dedicated Precise handle. The Authors compared the efficacy of haemostasis and the economical impact of the device, in terms of drug administration and costs. The Authors comparatively analyzed 120 total extracapsular thyroidectomies (TET) performed by the standard operative technique (Group A, control) and 70 TET achieved by the "sutureless technique" (Group B, case). There was a statistically significant decrease of transient postoperative hypocalcemia (5.71% vs 7.5%) and also of mean operative time (about 20 minutes) in patients of the group B. Non significant decrease of other kind of complications (postoperative hemorrhage, transient and permanent inferior laryngeal palsy, stupor of the superior laryngeal nerve, seromas) were also observed. The use of the Ligasure Precise resulted easy, safe and efficient in the Authors' experience. It allowed the decrease of postoperative haemorrhages and mean operative time.

Case-Control Studies↗
PubMed2005

Gastrointestinal tumours in elderly.

The Authors report their experience concerning 129 cases of gastrointestinal neoplasms (gastric, colonic, anorectal), recorded during the last years among patients aged between 70 and 81 years, who underwent radical surgery. The main issues evaluated were: anaesthesiological risk, stage, post-operative mortality and morbidity. Elderly seems not to be a contraindication, nor a limit for surgery if the patient is correctly and strictly managed pre and post-operatively.

Aged↗
PubMed2004

Immunohistochemical distribution of proteins belonging to the receptor-mediated and the mitochondrial apoptotic pathways in human placenta during gestation.

The balance between cell death and cell proliferation and its regulation are essential features of many physiological processes and are particularly important in fetal morphogenesis and adult tissue homeostasis. Apoptosis is a type of cell suicide that is activated in two main ways: through a receptor-mediated pathway or through a mitochondrial pathway. We have investigated the immunohistochemical distribution of proteins belonging to these two pathways in human placenta during gestation by comparing their expression levels between the first and third trimester of gestation. In the first trimester, the receptor-mediated pathway prevails over the mitochondrial pathway with a moderate/intense expression of its three components, viz., Fas ligand (FasL), Fas, and caspase-8, and weak positivity of anti-apoptotic FLIP, these proteins being mainly localized in the cytotrophoblast compartment. In the third trimester of gestation, there is an increased expression of mitochondrial pathway proteins, viz., Apaf-1 and caspase-9. We have also investigated the expression level of caspase-3, the primary effector caspase of both pathways, and have observed that it is moderately expressed during gestation, being mainly localized in the cytotrophoblast during the first trimester and in both placental compartments during the third trimester of gestation. Thus, both pathways actively function in human placenta to execute cell death. By means of immunoelectron microscopy, we have further shown that, in human placenta, the two proteins of the mitochondrial pathway together with caspase-3 are localized both in the cytoplasm and in the nucleus. In particular, Apaf-1 and caspase-9 are distributed near to the nuclear envelope suggesting an important role for these two proteins in disrupting the nuclear-cytoplasmic barrier.

Adult↗
PubMed2004

Pattern of expression of cyclin D1/CDK4 complex in human placenta during gestation.

Progression through the cell cycle in eukaryotic cells is controlled by a family of protein kinases, termed cyclin-dependent kinases (CDKs), and their specific partners, the cyclins. In particular, the control of mammalian cell proliferation occurs largely during the G1 phase of the cell cycle. Five mammalian G1 cyclins have been enumerated to date: cyclins D1, D2, and D3 (D-type cyclins), and cyclins E and E2. By the use of immunohistochemistry and immunoelectron microscopy, we observed that in the first trimester of gestation of human placenta, cyclin D1 was distributed in the nuclei of the cytotrophoblast compartment together with a weak positivity of endothelial cells surrounding blood vessels. The endothelial positivity of cyclin D1 strongly increased in the third trimester of gestation. Moreover, we observed the subcellular localization of cyclin D1 that was present both in the stroma of placental villi and in the nuclei of syncytiotrophoblast cells. Therefore, we observed that CDK4 was localized in the nuclei of the cytotrophoblast compartment during the first and third trimesters and it also had a nuclear positivity in the endothelial cells of blood vessels at the end of the third trimester of gestation. In conclusion we may hypothesize that cyclin D1/CDK4 complex functions to regulate the cell cycle progression in the proliferative compartment of human placenta, the cytotrophoblast, during the first trimester through interaction with p107 and p130. Therefore, cyclin D1 and CDK4 seem to be involved in the control of placental angiogenesis during the third trimester of gestation.

Cell Cycle↗
PubMed2004

Annual variations of adrenal gland hormones in the lizard Podarcis sicula.

The adrenal gland regulates metabolism and maintains normal electrolyte balance. Adrenal hormones are equivalent in all vertebrates; the chromaffin tissue produces adrenaline and noradrenaline and the steroidogenic tissue produces most of the steroid hormones present in mammals. Podarcis sicula belongs to the Squamata family of lizards and it is the most abundant lizard species in southern Italy. This species shows a reproductive annual cycle and the presence of seasonal variations in the activity of the hypothalamus-hypophyseal-thyroid axis. To investigate the existence of an annual cycle of lizard adrenal gland, we have measured plasma concentrations of corticosterone, ACTH, noradrenaline and adrenaline. We have shown that corticosterone rapidly increased from January to March to reach a peak value that persisted until July, then, it slowly decreased until December. ACTH levels increased from January to May and slowly decreased from July to December. Noradrenaline levels were higher in March and then decreased until December. On the contrary, adrenaline levels increased from March to July and slowly decreased until December. Our results demonstrate the existence of an annual cycle of the lizard adrenal gland activity. This is very interesting because its activity is important to rightly regulate the reproductive status of the Podarcis sicula lizard.

Adrenal Glands↗
PubMed2003

Shift from noradrenaline to adrenaline production in the adrenal gland of the lizard, Podarcis sicula, after stimulation with vasoactive intestinal peptide (VIP).

The aim of this study was to investigate the distribution and function of VIP in the adrenal gland of the lizard, Podarcis sicula. We have shown by immunohistochemistry that VIP fibers were localized exclusively around clusters of chromaffin cells in the dorsal ribbon of the lizard adrenal gland. Moreover, a strong positivity for this peptide was observed within ganglial cells and within most chromaffin cells of the gland. To investigate the effects of VIP on the adrenal gland, we have treated lizards with several doses of this peptide and we have shown that injections of exogenous VIP increased plasma levels of catecholamines and corticosteroids, but not of ACTH. This probably suggests a direct effect of VIP on the control of adrenal hormone secretion without the involvement of the hypothalamo-hypophyseal axis. Our results also establish that the increased levels of the hormones were modulated in a time- and dose-dependent manner. Therefore, our morphological studies showed a clear increased function of steroidogenic cells. In the medullary region, VIP administration induced not only a functional enhancement of adrenaline release from adrenergic cells, but also a shift of noradrenaline cells to adrenaline ones.

Adrenal Cortex Hormones↗
PubMed2003

Immunocytochemical localization of substance P in the adrenal gland of Podarcis sicula (Reptilia, Lacertidae): evidence for its involvement in the modulation of adrenal activity.

The occurrence of substance P (SP) immunoreactivity was investigated in the adrenal gland of the lizard Podarcis sicula by ABC immunocytochemical technique: SP-immunoreactivity was present in both adrenaline and noradrenaline cells, in ganglion cells and nerve fibers in the connective capsule surrounding the gland. The involvement of substance P in the modulation of pituitary-interrenal axis was studied in vivo by intraperitoneal injections of SP. The effects were estimated by means of the morphological and morphometrical features of the tissues, as well as the plasma levels of adrenocorticotropic hormone (ACTH), corticosterone and catecholamines, adrenaline and noradrenaline. Substance P (0.07 mg/100 g body wt) decreased ACTH plasma levels and raised corticosterone release from steroidogenic tissue, that showed clear signs of stimulation. In the chromaffin tissue, the decrease in the number of noradrenaline cells, and the increase in the number of adrenaline cells, lowered numeric noradrenaline/adrenaline cell ratio. Moreover, an increase in adrenaline plasma level and a decrease in noradrenaline plasma level were found. The results suggest that (1) also in Reptiles as in other Vertebrates, SP may affect pituitary-adrenal axis activity, and (2) the chromaffin cells may be involved in the paracrine control of steroidogenic activity.

Adrenal Glands↗
PubMed2003

Effects of gonadotropin-releasing hormone agonists on uterine volume and vasculature and on the immunohistochemical expression of basic fibroblast growth factor (bFGF) in uterine leiomyomas.

We investigated the effect of the GnRH agonist (GnRH-a) on the uterine volume and on the immunohistochemical expression of basic fibroblast growth factor (bFGF) and the vasculature of leiomyomas. Twenty-five women were treated with leuprorelin acetate for 3 months; 46 untreated patients were enrolled as a control group. The uterine volume was measured by ultrasonography. After myomectomy or hysterectomy, the immunoexpression of bFGF and the endothelial marker, CD34, was studied and compared in treated and untreated leiomyomas. Uterine volume decreased after therapy. The number of cells expressing bFGF and the vascularity were diminished in treated leiomyomas. Reduction in the blood supply might be responsible, in part, for uterine-volume shrinkage after GnRH-a therapy.

Adult↗
PubMed2003

[Cancer risk in breast lesions: diagnostic and therapeutic strategy].

BACKGROUND: The classification, diagnostic recognition and surgical treatment of breast lesions at risk of neoplastic transformation represent some of the most important objectives in breast research. Attention has been focused on lesions at risk of neoplastic transformation in breast pathology, such as: atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), multiple intraductal papilloma and sclerosing adenosis. METHODS: Our experience regards activity carried out from 1996 to 2001; the diagnostic approach included routine performance of echotomographic examination, mammography screening indicated in women >40 and, in selected cases, in women <40; FNAB was carried out in all lesions containing suspicious cells. In the case of non-palpable lesions we carried out a CT-guided FNAB using the stereotaxic technique. In cases of secreting breast, galactography proved useful. As regard clinically suspect nipple secretions, cytology was useful in the diagnosis of intraductal papillomatous lesions. Surgery was indicated for: mammographically negative nodular lesions with cytological finding of suspect lesions. Continuous, spontaneous mono-orificial, serous, sero-hematic or hematic secretion of the nipple also in the presence of negative and/or inconclusive galactographic and cytological findings. From a nosological viewpoint we have distinguished 3 groups: A) 49 women (average age 47.3 years) with suspect lesions subjected to biopsy. On the basis of the cytological response we carried out: 37 quadrantectomies with extemporary examination, 4 excisional biopsies, 5 radical ductectomies and 3 microductectomies. B) 26 patients (36.7 years) subjected to mammary biopsy for non-suspect lesions; in 24 cases excisional biopsy of the lesion and in 2 cases radical ductectomy. C) Control group consisting of 141 women (average age 44.5 years) suffering from benign pathology not suspected of lesions at risk and not subjected to surgery. RESULTS: The final histological examination evidenced: Group A: 7 cases of T1aN0M0 carcinoma (14.3%); 20 lesions at risk (40.8%); 22 lesions not at risk; Group B: 25 (96.1%) lesions not considered at risk, in 1 case (3.9%) area of sclerosing adenosis with ductal proliferation and slight atypias; Group C: in 4 cases (3.1%) the onset at follow-up of lesions at risk made it necessary to remove the lesion. Histology did not confirm the presence of cancer in any case. CONCLUSIONS: The diagnostic and therapeutic protocol proposed enables us to identify and radically treat high risk patients (Group A) and follow them up closely. On the contrary, Group B evidenced a very low incidence of lesions at risk which escaped preoperative diagnosis and in confirmation of this in Group C, during follow-up, the onset of only 4 lesions at risk was identified in which histological examination however excluded the presence of cancer.

Adult↗
PubMed2002

Atrial natriuretic factor in amniotic fluid and in maternal venous blood of pregnancies with fetal cardiac malformations and chromosomal abnormalities.

OBJECTIVE: We evaluated the levels of atrial natriuretic factor (ANF) in amniotic fluid and in maternal venous blood in pregnancies with fetal cardiac malformations and chromosomal abnormalities. METHOD: Between the 16th and 18th week of pregnancy, 151 women were divided into three groups. Group A included patients at lowest risk, carrying a fetus with a normally developing heart and normal karyotype (control group). Group B included women with a fetus suffering from cardiac malformations, with or without associated chromosomal abnormalities. Group C included women carrying a fetus affected with chromosomal abnormalities without congenital cardiopathies. ANF was evaluated by radioimmunoassay. RESULTS: In maternal venous blood, the mean levels of ANF were 42.1, 53.1 and 38.7 pg/ml in groups A, B and C, respectively. In amniotic fluid, the mean levels of ANF were 34.2, 101.8 and 35.8 pg/ml in groups A, B and C, respectively. In group A (control group) there was no statistical difference in ANF levels across the gestational age range of 16-18 weeks, either in amniotic fluid or in maternal venous blood. A significant difference of ANF content in maternal venous blood was revealed in comparing group A with group B (p < 0.01), and group C with group B (p < 0.01). A statistically significant difference in ANF levels was also found in amniotic fluid between group A and group B (p < 0.01), and between group C and group B (p < 0.01). No statistically significant differences were found between group C and group A in comparing ANF levels in maternal venous blood and amniotic fluid. CONCLUSION: ANF levels in amniotic fluid and in maternal venous blood are increased early in the case of fetuses with cardiac malformations, with or without associated karyotype alteration. Chromosomally abnormal fetuses without heart malformations have normal ANF levels. These results could be useful for elucidating fetal pathophysiology mechanisms.

Adult↗
PubMed2002

[Post-thyroidectomy hypocalcemia. Personal experience].

BACKGROUND: The study evaluates the incidence of both early and protracted post-thyroidectomy hypocalcemia over a 6-year period (1995-2000) in a series of 330 consecutive thryoid operations. The aim was to identify the profile of patients with the greatest risk of permanent parathyroid functional insufficiency and a suitable treatment protocol. METHODS: Having performed a statistical ana-lysis of all the variables, we divided the entire population of 330 patients into 4 groups based on the extent of demolition, the method of organotherapeutic replacement with L-Thyroxine and the (eco-radioguided) procedure used to identify the parathyroids: 59 patients undergoing subtotal thyroidectomy; 155 patients undergoing total thyroidectomy who commenced replacement organotherapy from postoperative day 15-30; 94 patients undergoing total thyroidectomy who commenced replacement organotherapy from postoperative day 1; 22 patients undergoing total thyroidectomy who underwent routine intraoperative parathyroid assay. RESULTS: The results show that the impact of more radical surgery in determining hypocalcemia, in particular protracted hypocalcemia, represents the most striking characteristic of patients with the greatest probability of permanent parathyroid insufficiency. We emphasise that early correction of postoperative hypothyroidism can drastically reduce the incidence of both early and protracted hypocalcemia. CONCLUSIONS: In conclusion, hypoparathyroidism is an exceptional event, whereas hypocalcemia is relatively common after total thyroidectomy. The effects of the early correction of postoperative hypothyroidism are undoubtedly beneficial, as is the use of eco- and radioguided methods for the intraoperative identification of the parathyroid glands, although they are not free from limits and criticism.

Adult↗
PubMed2002

[Prenatal telemedicine and teledidactic networking. A report on the TOCOMAT project].

Telemedicine originates with the combined use of electromedical equipment, information technologies and telecommunication systems designed to improve healthcare by overcoming the limitations of time and space. Moreover, telemedicine also possesses greater didactic potential than instruction by traditional means. Teledidactic networking, both as e-learning and e-teaching, represents a new integrated system of computer-aided education for the development and management of distance learning programs. Our study evaluated the effectiveness of teledidactic applications in the first Italian project in conventional and computerized telecardiotocography (TOCOMAT). Five cardiotocography outpatient monitoring facilities were linked telematically to a university central operating unit to obtain computerized analysis of telecardiotocographic (CTG) tracings and specialist consulting. The peripheral site operators received theoretical-practical training in the function and use of the system, the guidelines for CTG tracing interpretation and the diagnostic-therapeutic protocols. Improvement in learning progress was observed in the reduction of technical errors in CTG recording and in the increased ability of the outpatient clinic staff to select, analyze and interpret test RESULTS. Results from the feedback questionnaires on the didactic impact of the project indicated objective improvement in the specific skills acquired by the physicians at these facilities. The findings also show that a well-structured distance learning course can improve clinical, technical and managerial skills and behavior of healthcare operators by promoting the kind of professional continuing education a modern medical school should provide.

Female↗
PubMed2001

Alteration of the Bcl-2:Bax ratio in the placenta as pregnancy proceeds.

The placenta is the primary site of nutrient and gas exchange between mother and foetus. During human placental development, proliferation, differentiation and apoptosis occur at different stages. In order to clarify some of the molecular mechanisms underlying these events, we investigated the pattern of expression of two members of the Bcl-2 family in human placenta samples and compared them to the level of apoptosis detected by the TUNEL method. In particular, we evaluated the expression of Bcl-2 and Bax and their ratio during the first and third trimester. We found that Bcl-2 was generally expressed at low levels during the entire gestational period. On the other hand, Bax was low during the first trimester but increased towards the end of gestation. In accordance with the change of ratio of these two molecules, the increase of apoptotic cells was observable in the third trimester. These data indicate that Bcl-2 and Bax are spatio-temporally regulated during placental development and that the different expression of the above mentioned genes is at least in part responsible for the delicate balance between cell proliferation and programmed cell death in the human placenta during pregnancy.

Adult↗