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Biomedical subjects

V Esposito

Publications and source records attributed to V Esposito.

At least 19 recordsLinked to original sources

Effects of gonadal steroids on the growth of human pituitary adenomas in vitro.

The effects of testosterone (T), dihydrotestosterone (DHT) and methyltrienolone (R 1881) on cell proliferation of eight human pituitary tumors in culture wre assessed by [3H]thymidine incorporation and compared to those of progesterone (Pg) and 17 beta-estradiol. Receptors for androgens (AR), estrogens (ER) and progesterone (PgR) were characterized. AR had a significant inhibitory effect on all AR-positive tumors, whatever their hormonal content. Inhibitory effects of either T and DHT < R1881 < Pg were observed in tumors co-expressing AR and PgR. The inhibitory effect of R 1881 on a PgR-positive/AR-negative tumor suggested that R 1881 action was partially PgR-mediated. The effects of either T or the nonaromatizable DHT and R 1881 were unrelated to ER expression. We conclude that AR can modulate the growth of human pituitary tumors through direct receptor-mediated intracellular pathways which may be common to various pituitary cell types.

Adenoma

Acute and chronic effects of human recombinant GH (hrGH) on adrenal steroidogenesis in children affected with isolated GH deficiency (IGHD).

In a previous study we demonstrated that, in children affected with isolated GH deficiency, an acute high-dose human recombinant GH (hrGH) treatment increases the 11-deoxycortisol and induces an IGF-I responsiveness to ACTH. The aim of the present study was to reevaluate, in the same children, the adrenal and IGF-I responsiveness to ACTH after a chronic replacement-dose GH therapy. Ten children (seven males and three females, mean age 7 years) affected with isolated GH deficiency underwent a synthetic ACTH 1-17 test before and after sc administration of human recombinant GH at a dose of 0.6 UI/kg/week for 3 months. After therapy, the 11-deoxycortisol responsiveness to ACTH significantly decreased compared with that observed after acute treatment (P < 0.001), and so it returned to baseline. No differences were detected in the responsiveness to ACTH of cortisol, dehydroepiandrosterone-sulphate, D4-androstenedione, and 17-hydroxyprogesterone. On the other hand, the chronic treatment induced an IGF-I responsiveness to ACTH (P < 0.001). In conclusion, our study demonstrates that, in isolated GH deficiency, replacement doses of hrGH do not modify the adrenal steroid basal levels or its responsiveness to ACTH, whereas both replacement and high doses of hrGH induce an IGF-I responsiveness to ACTH.

17-Ketosteroids

[Assessment of dispersion++ of ventricular recovery in patients with chronic obstructive pulmonary disease].

Cardiac arrhythmias are common in patients with chronic obstructive pulmonary disease. Several factors may contribute to the development of arrhythmias in these patients including hypoxemia, hypercapnia, acid-base disturbances. The aim of the study was to assess QTc dispersion in patients with chronic obstructive pulmonary disease, who are at high risk of arrhythmias. Interlead QT variability as measured on the 12-lead electrocardiogram is not a technical artifact but probably reflects regional differences in ventricular repolarization. Increased dispersion of ventricular recovery time is believed to provide a substrate which supports serious ventricular arrhythmias. We showed that in patients with chronic obstructive pulmonary disease, free of underlying structural heart disease, the QTc dispersion is significant greater (p = 0.036) than in a control group, despite a similar value in mean QTc value. The data of the present study suggest that the determination of dispersion of repolarization times may be affected by metabolic changes occurring in patients with chronic obstructive pulmonary disease.

Adult

Ultrastructural observations on cytotoxic effector cells infiltrating pancreatic islets of low-dose streptozocin treated mice.

The aim of this study was to observe the ultrastructural events, during the onset of diabetes mellitus in the low-dose streptozocin (LDS)-treated mouse model with emphasis on the infiltrating elements. Forty male C57 BL/6J mice were given 40 mg/streptozocin on 5 consecutive days and killed 5, 6, 7, 8, 9, 10, 15, and 18 days after the first injection. Results demonstrated that islet infiltration occurring in LDS-treated mice is characterized by a very early pre-infiltration state in which mononuclear phagocytes in islet capillary vessels were considerably increased in number. A new histopathological time sequence for the early insulitis is described, in which attraction of blood mononuclear phagocytes into the islet capillary lumen is the first step. During the successive stage, occurring on days 6-8 we observed that mononuclear phagocytes migrate through capillary and venule walls into the islet parenchyma, where they differentiate into tissue macrophages. It was only later (step 3) that these macrophages acquired novel properties, typical of their "activated state" and started to phagocytose islet beta-cell debris. These data suggest that during the pre-infiltration and early insulitis the mononuclear phagocyte system plays a key role in the onset of LDS diabetes.

Animals

Extrahepatic portal vein aneurysm: report of a case treated by thrombectomy and aneurysmorrhaphy.

Extrahepatic portal vein aneurysm is a rare condition with only 15 cases before ours being reported in the English literature. The etiology is thought to be congenital, secondary to portal hypertension or associated with abnormal weakness of the vein wall. It often presents in conjunction with major gastrointestinal bleeding, but may occur with minimal or no symptoms. Diagnosis is made with color duplex ultrasound, computed tomographic scan, venous phase mesenteric angiography, magnetic resonance imaging, or splenoportography. Thrombosis, rupture, and pressure effects are the major complications of portal vein aneurysm. Shunting procedures are recommended in cases with portal hypertension secondary to liver disease. We report the first case treated by thrombectomy and aneurysmorrhaphy with a successful 10 year follow-up. This procedure should be considered to preserve portal vein flow when portal hypertension is absent or is secondary to the aneurysm itself.

Adult

Further evaluation of IGF-I responsiveness to ACTH in children affected with IGHD.

In our previous studies we had demonstrated that, in children affected with isolated GH deficiency (IGHD), a short-term recombinant growth hormone (rGH) therapy increases the 11-deoxycortisol (S) secretion and induces an IGF-I responsiveness to the ACTH challenge. The aim of the present study was to further investigate the mechanisms by which IGF-I is secreted after ACTH challenge in children affected with IGHD by correlating IGF-I versus cortisol (F) time courses after ACTH administration. Ten children affected with IGHD were subjected to rGH therapy (4 IU/day subcutaneously) for 10 days. The responsiveness of IGF-I, F and S to the ACTH 1-17 test were evaluated before and at the end of the therapy. No IGF-I response to the ACTH test was recorded in the patients before the rGH treatment, whereas after rGH administration ACTH induced a significant IGF-I release (p < 0.001) which started at the 1st hour, reached a peak value between the 5th and 6th hours and disappeared at the 10th hour. In conclusion, our study confirms that a short-term rGH therapy induces an IGF-I responsiveness to ACTH and helps to better define the kinetics and the mechanism of this IGF-I response to ACTH.

Adrenocorticotropic Hormone

Immunomodulation of low dose streptozocin diabetes in mice reveals that insulitis is not obligatory for B cell destruction.

Twenty male C57Bl/J mice were injected with 50 microliters complete Freund's adjuvant (CFA) 1 wk before and 1 wk after induction of diabetes with 45 mg streptozocin (STZ)/kg body weight i.p. over 5 d. CFA administration prevented islet infiltration. Inflammatory cells were not seen within any of the islets observed. However, islet B cell destruction still occurred. These cells showed evidence of considerable damage, containing swollen mitochondria, contracted nuclei and areas of vacuolation and degranulation. Inflammation is therefore not obligatory for the development of low dose STZ induced diabetes.

Animals

Pulmonary embolism in neurosurgical patients.

We report the outcome of a retrospective study on the frequency of pulmonary embolism during the hospital stay in a series of 7,250 neurosurgical patients. Of 4,500 patients who underwent surgery 25 (0.55%) developed pulmonary embolism at some point after the operation while 5 of the 2,750 patients not operated on (0.18%) developed a fatal pulmonary embolism. We analyze the general risk factors--age, sex, length of stay and paralysis of the limbs. Meningioma was the most frequent intracranial tumor to be affected by this complication. We discuss the connection between thromboembolism and meningioma.

Adult

Further morphological and biochemical observations on early low dose streptozocin diabetes in mice.

Conflicting published data regarding the role of macrophages and other cell types during the early stages of diabetes mellitus led us to further study this problem. To this end we diabetized mice, using low doses of streptozocin (STZ), 40 mg/kg body wt/day/5 days, and processed their pancreatic tissue for immunocytochemistry and ultrastructural observations; immunohistochemistry was performed on days 5 and 18 after the first STZ injection, and islets were observed ultrastructurally on days 5, 9, 10, and 18. Animals were tested for fasting serum glucose, and isolated islets were assayed for insulin secretion capacity. Immunohistology demonstrated that expression of major histocompatability complex class 2 antigens is strongly induced by multiple, low dose STZ treatments prior to impaired insulin release, and that different types of cells within the islet are capable of expressing Ia molecules. Ultrastructurally we found (a) a small number of macrophages (most probably resident monocytes/macrophages) containing B-cell debris, that were located close to either damaged or intact B cells; (b) a large number of recruited macrophages in a vascular or perivascular position; and (c) macrophages recognizable in the exocrine portion, close to the islets, occasionally containing exocrine cell debris. This led us to believe that recruited macrophages play an important role in the early islet-infiltrating stage.

Animals

Medium-term cyclosporin renal dysfunction and its reversibility in rats.

Renal dynamics and morphology were investigated by metabolic, renal micropuncture (RM), and electron microscopy (EM) studies in 50 female rats treated with cyclosporin A (CsA, 40 mg.kg body wt-1.48 h-1) for either 10, 20, or 30 days (groups CsA 10, CsA 20, and CsA 30, respectively); control rats received olive oil (group N). Body weight gain, sodium metabolism, and plasma volume were not altered by CsA administration in any group. GFR was decreased in group CsA 10 vs. group N (-10%, P less than 0.05) and was further impaired in groups CsA 20 and CsA 30 (-45%, P less than 0.01 vs. group N). RM studies showed a significant decrease of single-nephron glomerular filtration rate (SNGFR) in group CsA 30 vs. group N (-26%, P less than 0.01) after the fall of glomerular capillary pressure (Pgc;-8%, P less than 0.05), the increase of afferent arteriole resistance (Ra; +40%, P less than 0.05), and the consequent decrease of glomerular plasma flow (GPF; -28%, P less than 0.05). Thirty days after CsA withdrawal, SNGFR returned to normal values (P less than 0.01 vs. group CsA) as a result of the normalization of Pgc, Ra, and GPF.EM showed only a progressive vacuolation of proximal and distal tubular cells. These data suggest that medium-term administration of CsA is associated with reversible changes in glomerular dynamics and only mild histological lesions.

Animals

Early macrophage infiltration in mice treated with low-dose streptozocin decreases islet superoxide dismutase levels: prevention by silica pretreatment.

It has been hypothesized that streptozocin (STZ) given in low doses for 5 consecutive days produces diabetes by induction of peroxidation phenomena similar to those induced by free radicals. Moreover, it has been demonstrated that macrophages are among the first to invade the pancreatic parenchyma and destroy islet B cells supposedly by the release of interleukin-1 that induces free radical formation. Superoxide dismutase (SOD) is a free radical scavenger present in cells, and islet B cells are known to have extremely low levels of this enzyme. Therefore, our aim was to observe SOD activity concomitantly with the appearance of intra-islet macrophages, in early diabetes induced by low-dose streptozocin (LDS). Silica-pretreated mice showed SOD values which were comparable to those found in control animals. In LDS-only-treated mice we found that SOD levels were decreased even after only 4 days from the last STZ injection and that it is at this time that the first 'recruited' macrophages appear in the islets. Moreover, the SOD levels found at this early stage (animals were still normoglycaemic and therefore not as yet diabetic) were similar to levels found by us in a previous work, in prediabetic Bio Breeding rats, thereby ascribing a crucial factor to the lowering of SOD levels even in LDS-induced diabetes.

Animals

A comparison of computerized tomography-guided stereotactic and ultrasound-guided techniques for brain biopsy.

Forty-one patients with brain lesions underwent brain biopsy using either a computerized tomography (CT)-guided stereotactic approach or an ultrasound-guided technique. The cases were selected according to location and size of the mass lesion. Lesions 15 mm or less in diameter and those in the posterior fossa were biopsied by a CT-guided stereotactic technique (18 patients). Supratentorial lesions with a diameter larger than 15 mm were approached using ultrasound guidance (23 patients). These criteria for procedure selection provided a diagnostic yield of 94% for the CT-guided procedures and 91% for those guided by ultrasound. Safety for the two procedures was similar. The ultrasound procedure was more rapid, simpler, and less costly to perform. It is concluded that, with the protocol described, CT-guided stereotactic procedures could be reserved for cases in which absolute accuracy is mandatory.

Biopsy

Islet B cell neoproliferation in early low dose streptozocin induced diabetes in mice: a ducto-endocrine proliferation?

Several authors have documented cases of newly forming B cells from ductules of diabetic animals in their studies but few have enlarged on this phenomenon. We, therefore, diabetized 15 mice, with low dose injections of streptozocin (STZ) for 5 days, and observed their pancreatic islets 6 (group 1) and 14 (group 2) days after the last STZ injection in order to further the argument. We found that: i) mice without infiltration of their islets did not present any newly formed B cells; ii) mice belonging to group one, showing a mild or scarce lymphomonocytic infiltration, had a few (one or two) newly formed B cells; iii) mice belonging to group two, showing a massive islet infiltration, had two to three neoformed B cells; iv) we observed in one animal intact newly formed islets of Langerhans with a clearly observable ductule within each of them, as in a case of nesidioblastosis. All these neoformations occurred in animals with very low insulin levels. Morphometric evaluations did not show any significant modification in the number of D cells in group one animals when compared to control D cell numbers, but showed an increase in group two animals. We believe that the formation of these newly formed B cells, that might be named "ducto-endocrine proliferation", is an attempt to compensate for the loss of B cells at the onset of the diabetic syndrome.

Animals

Capillary area in early low-dose streptozocin-treated mice.

It has been reported that vasoconstriction of intra-islet capillaries plays an important role in the initiation of the insulitis seen in the islets of Langerhans of diabetic animals. Nevertheless, only a few studies have concentrated on islet vessels. This led us to perform an experiment with the aim to compare the islet capillary area of normal untreated and multiple low-dose streptozocin (LDS) (40 mg/kg b.wt. i.p./5 days)-treated mice. In order to identify endothelial cells a method devised by Gomori, based on the fact that these cells present alkaline phosphatases on their surface, was used. Results revealed that in LDS-treated animals the capillary area per islet is significantly reduced when compared to the vascular area of controls (p less than 0.05). This could be due to a vasoconstriction phenomenon that occurs in the islet capillaries after the streptozocin administration and before the appearance of any inflammation. Our findings could demonstrate that vasoconstriction events are involved in initiation of the diabetic disease.

Alkaline Phosphatase

Amphotericin B-induced depression in the phagocytic function of the isolated rat liver and its prevention by nifedipine.

We investigated the effects of the antimycotic agent amphotericin B (AmB) on the phagocytic activity of the isolated perfused rat liver. At a concentration of 5 microM, the drug markedly reduced the clearance of latex beads by the liver as compared to control preparations. Scanning electron microscopy observations showed that latex beads were attached only to Kupffer cells. A liver scan performed infusing 99Tc-colloidal albumin showed that AmB depressed the uptake of the colloid in all hepatic lobes, with no focal defects. Both in control and AmB experiments no trypan blue uptake occurred. The pretreatment of the perfused liver with the calcium antagonist nifedipine prevented the decrease in phagocytosis induced by AmB. In addition, AmB had no effect on livers perfused with a Ca2(+)-free medium. A decrease in the phagocytic capacity of the perfused liver was also observed after the administration of the Ca2(+)-ionophore A23187. The observations suggest that AmB may exert an intrinsic toxicity on the Kupffer cells, which is, at least in part, responsible for the decrease in phagocytosis induced by the drug. This effect may be of relevance to clinical situations and deserves careful consideration.

Amphotericin B

Ciclosporin administration during pregnancy induces ultrastructural changes on pancreatic beta-cells of newborn rats.

Ciclosporin (CS) is an immunosuppressive agent used in the prevention of graft rejections and in the management of type 1 diabetes. However, the drug is not without side effects. The aim of this study was to evaluate eventual cytotoxic phenomena in the pancreas of newborn rats whose mothers had been treated with therapeutic doses of CS. For this purpose, 25 female Wistar rats were used, 20 of which were subjected to daily injections of 10 mg/kg BW/day i.p. of CS dissolved in Intralipid, administered during the whole gestational period. The results obtained indicated that CS did not arrest fetal development, even though the number of newborns per mother was reduced when compared to controls. Moreover, mothers and newborn rats were subjected to vacuolation of kidney proximal tubular cells and of the insulin-secreting pancreatic beta-cells. This alteration was more evident in the islet beta-cells of newborn rats. Therefore, CS is not only toxic to the mothers' endocrine beta-cells but also to those of any eventual offspring.

Animals

Hemorrhagic pituitary adenomas: clinicopathological features and surgical treatment.

Forty-five (9.9%) of 453 pituitary adenomas operated on between January 1973 and November 1988 demonstrated hemorrhagic changes at surgery: 24 had a blood collection, 12 had a blood collection associated with hemorrhagic necrosis, and 9 had hemorrhagic necrosis. Thirteen patients (28.9%) experienced the acute symptoms of pituitary apoplexy, whereas another 32 had an "asymptomatic" hemorrhage, that is, the clinical course was comparable to an uncomplicated adenoma. Nineteen tumors (42.2%) showed marked suprasellar extension, 8 (17.8%) showed moderate extension, and 11 (24.5%) showed slight extension; another 2 (4.4%) were laterosellar and 5 (11.1%) were intrasellar. Invasive behavior was present in 32 cases (71.1%) and this may suggest another hypothesis to explain the pathogenesis of tumoral hemorrhage. The incidence of hemorrhagic complications in invasive adenomas with marked suprasellar extension was particularly impressive; therefore, we do not suggest preoperative bromocriptine treatment in this type of tumor. Two of 14 patients operated on by the transcranial route died after surgery, whereas there was no operative mortality in the 31 patients operated on by the transsphenoidal route. It proved advantageous to operate as early as possible, even during the acute phase of pituitary apoplexy. The transsphenoidal approach gave the best results, but to achieve satisfactory late results multidisciplinary treatment was necessary, namely, postoperative radiotherapy in 23 patients, bromocriptine in 12, and endocrine replacement therapy in almost all. In an average follow-up period of 6.2 years, 5 (11.1%) symptomatic recurrences were observed.

Adenoma

Effects of amphotericin B on the excretory function and the colloid clearance capacity of the perfused rat liver.

The effects of amphotericin B (AmB) on the hepatic excretory function and the colloid clearance capacity were investigated in the perfused rat liver. AmB at 5 or 10 microM caused dose-dependent reductions in bile and perfusate flow rates and in biliary bile acid (BA) excretion. BA concentration in bile tended to increase, due to a prominent reduction in bile water induced by the drug. At 5 microM, AmB also caused an increase in [14C]sucrose clearance by the liver and a release of hepatocytic enzymes into the perfusate. These alterations were not related to the decrease in the perfusate flow induced by AmB. In addition, the drug, at 5 microM, caused a significant decrease in the colloidal carbon clearance by the liver. In this case also, the effect was independent of the reduction in the perfusate flow induced by the drug. The toxic effects of AmB on the rat liver could be interpreted as a derangement of the cell membrane functional integrity, which causes cholestasis, enzyme leakage and an impairment of the reticuloendothelial system function. This latter effect deserves careful evaluation of its clinical implications.

Amphotericin B