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P Castaldo

Publications and source records attributed to P Castaldo.

At least 37 records · Page 2Linked to original sources
PubMed1998

herg encodes a K+ current highly conserved in tumors of different histogenesis: a selective advantage for cancer cells?

The human ether-a-go-go-related gene (herg) encodes a K+ current (IHERG) that plays a fundamental role in heart excitability by regulating the action potential repolarization (IKr); mutations of this gene are responsible for the chromosome 7-linked long QT syndrome (LQT2). In this report, we show that in a variety (n = 17) of tumor cell lines of different species (human and murine) and distinct histogenesis (neuroblastoma, rhabdomyosarcoma, adenocarcinoma, lung microcytoma, pituitary tumors, insulinoma beta-cells, and monoblastic leukemia), a novel K+ inward-rectifier current (IIR), which is biophysically and pharmacologically similar to IHERG, can be recorded with the patch-clamp technique. Northern blot experiments with a human herg cDNA probe revealed that both in human and murine clones the very high expression of herg transcripts can be quantified in at least three clearly identifiable bands, suggesting an alternative splicing of HERG mRNA. Moreover, we cloned a cDNA encoding for IIR from the SH-SY5Y human neuroblastoma. The sequence of this cDNA result was practically identical to that already reported for herg, indicating a high conservation of this gene in tumors. Consistently, the expression of this clone in Xenopus oocytes showed that the encoded K+ channel had substantially all of the biophysical and pharmacological properties of the native IIR described for tumor cells. In addition, in the tumor clones studied, IIR governs the resting potential, whereas it could not be detected either by the patch clamp or the Northern blot techniques in cells obtained from primary cell cultures of parental tissues (sensory neurons and myotubes), whose resting potential is controlled by the classical K+ anomalous rectifier current. This current substitution had a profound impact on the resting potential, which was markedly depolarized in tumors as compared with normal cells. These results suggest that IIR is normally only expressed during the early stages of cell differentiation frozen by neoplastic transformation, playing an important pathophysiological role in the regulatory mechanisms of neoplastic cell survival. In fact, because of its biophysical features, IIR, besides keeping the resting potential within the depolarized values required for unlimited tumor growth, could also appear suitable to afford a selective advantage in an ischemic environment.

Amino Acid Sequence↗
PubMed1998

Magnetic resonance imaging in evaluation of the common bile duct.

BACKGROUND: The ideal method for evaluation of the common bile duct (CBD) before or during cholecystectomy remains controversial. Magnetic resonance cholangiography (MRC) is a new, promising technique. A prospective evaluation is reported. METHOD: Sixty-one patients (45 women) were studied by MRC. There were 29 patients with symptomatic gallstone disease and without clinical, biochemical or ultrasonographic evidence of CBD stones (group 1); 28 of them also underwent intraoperative cholangiography (IOC). In addition, there were 21 patients with symptomatic gallstone disease, with mild biochemical and ultrasonographic signs of CBD involvement (group 2), of whom 19 underwent IOC, and 11 patients with symptomatic CBD stones (group 3), nine of whom had preoperative endoscopic retrograde cholangiopancreatography (ERCP) following MRC. RESULTS: MRC showed that no patient in group 1 and three patients in group 2 had CBD stones. Three patients (one in group 1, two in group 2) did not undergo IOC because of technical or clinical problems. In group 3, ERCP confirmed the results of MRC in nine patients. Two patients underwent open surgery because of ultrasonographic, MRC and radiographic signs of pancreatic malignancy. CONCLUSION: MRC could replace IOC and ERCP for identification of asymptomatic CBD stones. In symptomatic patients MRC combined with other non-invasive imaging techniques can direct the surgeon to appropriate management.

Cholangiography↗
PubMed1998

Biliary atresia-polysplenia syndrome: surgical and clinical relevance in liver transplantation.

OBJECTIVE: To review a single center's 10-year experience with liver transplantation (LTx) for the biliary atresia-polysplenia syndrome (BA-PS) and to define surgical and clinical guidelines for its management. SUMMARY BACKGROUND DATA: BA is the most common indication for pediatric liver transplantation (LTx) and is associated with PS in 12% of cases. Only a few studies of LTx for BA-PS have been reported, and the optimal management of BA-PS patients undergoing LTx has yet to be determined. METHODS: From July 1985 to September 1995, 166 liver transplants were performed in 130 patients with BA and were included in the study. The malformations most commonly associated with BA-PS, surgical techniques used to overcome these anomalies, and surgical pitfalls that could have contributed to the outcome were characterized. Actuarial 10-year patient and graft survival for patients undergoing LTx for BA-PS were calculated and compared to those with isolated BA. RESULTS: Ten patients (7.8%) with BA had associated PS. An additional patient with PS without BA was included in the study. The diagnosis of PS was unknown before the transplantation in 72% of cases. Thirteen liver transplants were performed in these 11 patients. Modifications of the usual surgical technique were used to overcome the complex anatomy encountered. There was no association between the type of anomaly and the outcome, nor were there any significant differences in patient survival (72% vs. 73.5%, p = 0.79) or graft survival (56.4% vs. 54.6%, p = 0.54). CONCLUSIONS: The association of BA with various anomalies should be considered a spectrum that may vary widely from patient to patient. The finding of two or more of these malformations in a patient awaiting transplantation should lead the surgeon to look systematically for other associated anomalies. With some special surgical considerations, the outcome in BA-PS patients should not differ from those with isolated BA.

Biliary Atresia↗
PubMed1998

Reduction of advanced glycation end-product (AGE) levels in nervous tissue proteins of diabetic Lewis rats following islet transplants is related to different durations of poor metabolic control.

Advanced glycation end-products (AGEs) are irreversible compounds which, by abnormally accumulating over proteins as a consequence of diabetic hyperglycaemia, can damage tissues and thus contribute to the pathogenesis of diabetic complications. This study was performed to evaluate whether restoration of euglycaemia by islet transplantation modifies AGE accumulation in central and peripheral nervous tissue proteins and, as a comparison, in proteins from a non-nervous tissue. Two groups of streptozotocin diabetic inbred Lewis rats with 4 (T1) or 8 (T2) months disease duration were grafted into the liver via the portal vein with 1200-1500 islets freshly isolated from normal Lewis rats. Transplanted rats, age-matched control and diabetic rats studied in parallel, were followed for a further 4-month period. At study conclusion, glycaemia, glycated haemoglobin and body weight were measured in all animals, and an oral glucose tolerance test (OGTT) performed in transplanted rats. AGE levels in cerebral cortex, spinal cord, sciatic nerve proteins and tail tendon collagen were measured by enzyme-linked immunosorbent assay (ELISA). Transplanted animal OGTTs were within normal limits, as were glycaemia and glycated haemoglobin. Diabetic animal AGEs were significantly higher than those of control animals. Protein AGE values were reduced in many transplanted animals compared to diabetic animals, reaching statistical significance in spinal cord (P < 0.05), sciatic nerve (P < 0.02) and tail tendon collagen (P < 0.05) of T1 animals. Thus, return to euglycaemia following islet transplantation after 4 months of diabetes with poor metabolic control reduces AGE accumulation rate in the protein fractions of the mixed and purely peripheral nervous tissues (spinal cord and sciatic nerve, respectively). However, after a double duration of bad metabolic control, a statistically significant AGE reduction has not been achieved in any of the tissues, suggesting the importance of an early therapeutic intervention to prevent the possibly pathological accumulation of AGEs in nervous and other proteins.

Animals↗
PubMed1998

Molecular basis for the lack of HERG K+ channel block-related cardiotoxicity by the H1 receptor blocker cetirizine compared with other second-generation antihistamines.

In the current study, the potential blocking ability of K+ channels encoded by the human ether-a-go-go related gene (HERG) by the piperazine H1 receptor antagonist cetirizine has been examined and compared with that of other second-generation antihistamines (astemizole, terfenadine, and loratadine). Cetirizine was completely devoid of any inhibitory action on HERG K+ channels heterologously expressed in Xenopus laevis oocytes in concentrations up to 30 microM. On the other hand, terfenadine and astemizole effectively blocked HERG K+ channels with nanomolar affinities (the estimated IC50 values were 330 and 480 nM, respectively), whereas loratadine was approximately 300-fold less potent (IC50 approximately 100 microM). In addition, in contrast to terfenadine, cetirizine did not show use-dependent blockade. In SH-SY5Y cells, a human neuroblastoma clone that constitutively expresses K+ currents carried by HERG channels (IHERG), as well as in human embryonic kidney 293 cells stably transfected with HERG cDNA, extracellular perfusion with 3 microM cetirizine did not exert any inhibitory action on IHERG. Astemizole (3 microM), on the other hand, was highly effective. Terfenadine (3 microM) caused a marked (approximately 80%) inhibition of IHERG in SH-SY5Y cells, whereas loratadine, at the same concentration, caused a 40% blockade. Furthermore, the application of cetirizine (3 microM) on the intracellular side of the membrane of HERG-transfected human embryonic kidney 293 cells did not affect IHERG, whereas the same intracellular concentration of astemizole caused a complete block. The results of the current study suggest that second-generation antihistamines display marked differences in their ability to block HERG K+ channels. Cetirizine in particular, which possesses more polar and smaller substituent groups attached to the tertiary amine compared with other antihistamines, lacks HERG-blocking properties, possibly explaining the absence of torsade de pointes ventricular arrhythmias associated with its therapeutical use.

Animals↗
PubMed1997

Regulation of the human ether-a-gogo related gene (HERG) K+ channels by reactive oxygen species.

Human ether-a-gogo related gene (HERG) K+ channels are key elements in the control of cell excitability in both the cardiovascular and the central nervous systems. For this reason, the possible modulation by reactive oxygen species (ROS) of HERG and other cloned K+ channels expressed in Xenopus oocytes has been explored in the present study. Exposure of Xenopus oocytes to an extracellular solution containing FeSO4 (25-100 microM) and ascorbic acid (50-200 microM) (Fe/Asc) increased both malondialdehyde content and 2',7'-dichlorofluorescin fluorescence, two indexes of ROS production. Oocyte perfusion with Fe/Asc caused a 50% increase of the outward K+ currents carried by HERG channels, whereas inward currents were not modified. This ROS-induced increase in HERG outward K+ currents was due to a depolarizing shift of the voltage-dependence of channel inactivation, with no change in channel activation. No effect of Fe/Asc was observed on the expressed K+ currents carried by other K+ channels such as bEAG, rDRK1, and mIRK1. Fe/Asc-induced stimulation of HERG outward currents was completely prevented by perfusion of the oocytes with a ROS scavenger mixture (containing 1,000 units/ml catalase, 200 ng/ml superoxide dismutase, and 2 mM mannitol). Furthermore, the scavenger mixture also was able to reduce HERG outward currents in resting conditions by 30%, an effect mimicked by catalase alone. In conclusion, the present results seem to suggest that changes in ROS production can specifically influence K+ currents carried by the HERG channels.

Animals↗
PubMed1997

10-year experience of total thyroidectomy with special reference to 85 thyroid cancers in one Italian centre.

The ideal surgical approach for differentiated thyroid carcinomas (DTC) is a matter for debate. Total (TT) or near total (NT) thyroidectomy on one side, and lobectomy (LL) or lobo-isthmusectomy (LI) on the other side are the options. Extended (TT, NT) resections are preferable for several reasons, and LL or LI are preferred by some groups. Our 10-year experience indicates that the post-operative complications percentage may be low enough to make TT the preferred surgical option.

Adult↗
PubMed1997

Experience with enteric conversion after pancreatic transplantation with bladder drainage.

BACKGROUND: Bladder drainage by the duodenal segment technique is currently the preferred method of handling the exocrine secretions after vascularized pancreatic transplantation. Despite improving results, however, the management of metabolic and urologic complications associated with bladder drainage remains problematic. STUDY DESIGN: A retrospective survey was performed of a consecutive case series of 196 pancreatic transplantations in 186 patients with diabetes over an 80-month period. All patients underwent whole organ pancreatic transplantation with bladder drainage by the duodenal segment technique. RESULTS: A total of 25 conversions (13 percent) from bladder drainage to enteric drainage were performed in 24 patients (24 side-to-side duodenoenterostomies, one Roux-en-Y limb duodenoenterostomy). The mean time of enteric conversion after pancreatic transplantation was 22 +/- 18 months (range, 1 to 72 months). All but two of the enteric conversions were performed at least 6 months after pancreatic transplantation. Indications for enteric conversion included dehydration with intractable metabolic acidosis (n = 18; 9 percent), urologic complications (n = 5; 3 percent), or problems with the duodenal segment (n = 2; 1 percent). The mean length of hospitalization for enteric conversion was 12 +/- 7 days (range, 6 to 30 days). All patients experienced improvement in their symptoms after enteric conversion. Anastomotic leaks developed postoperatively in five patients; two were managed operatively and three were managed nonoperatively. Oral bicarbonate supplementation was eliminated in all but one patient after enteric conversion. Patient survival is 100 percent and pancreatic graft survival (insulin independence) is 96 percent after a mean follow-up of 22 months after enteric conversion. CONCLUSIONS: Enteric conversion after pancreatic transplantation with bladder drainage is a safe and effective therapy for refractory problems related to the duodenal segment, altered physiologic function, or urologic complications and should be considered after 6 months for patients with persistent side effects.

Adult↗
PubMed1997

Levels of advanced glycosylation end-products (AGE) in sera of pregnant diabetic women: comparison between type 1, type 2 and gestational diabetes mellitus.

The chronic hyperglycemia can lead to an increase of the advanced glycosylation end-products (AGE) levels on proteins and macromolecules. Abnormal levels of AGE in several tissues has been associated with the pathogenesis of late diabetic complications. In diabetic pregnant women, high AGE levels might influence the delicate maternal-fetal balance and therefore alter the pregnancy outcome. In this preliminary study, we have measured the AGE in sera of 44 diabetic women in two trimester. Sixteen sera from non diabetic pregnant women have been used as controls. The AGE have been analyzed by means of an ELISA method with an antiserum anti-RNAse-AGE, produced in the Laboratory of Clinical Biochemistry of the Istituto Superiore di Sanità. Diabetic patients type 1 and type 2, in good metabolic control, showed normal AGE levels at both trimester. Patients with gestational diabetes showed significantly high serum AGE levels (p < 0.05). A more extended study will give better insight on the association between AGE levels and a physiopathology of diabetic pregnancy.

Adult↗
PubMed1996

Protection by coenzyme Q10 of tissue reperfusion injury during abdominal aortic cross-clamping.

PURPOSE: To evaluate the effect of coenzyme Q10 in reducing the skeletal muscle reperfusion injury following clamping and declamping the abdominal aorta. METHODS: 30 patients undergoing elective vascular surgery for abdominal aortic aneurysm or obstructive aorto-iliac disease were randomly divided into two groups: patients in group I were treated with coenzyme Q10 (150 mg/day) for seven days before operation, and those in group II received a placebo. We studied the hemodynamic profile in each patient during clamping and declamping of the abdominal aorta. The plasma concentrations of thiobarbituric acid reactive substances (malondialdhehyde), conjugated dienes, creatine kinase and lactate dehydrogenase were measured in samples from both arterial and inferior vena cava sites. Serial sampling was performed after induction of anesthesia, 5 and 30 minutes after abdominal aortic cross clamping, 5 and 30 minutes after aortic cross-clamp removal. RESULTS: The concentrations of malondialdehyde, conjugated dienes, creatine kinase and lactate dehydrogenase in patients who received CoQ10 were significantly lower than in the placebo group. Decrease of plasma malondialdehyde concentrations correlated positively (p < 0.01) with decrease of both creatine kinase and lactate dehydrogenase release in samples from the inferior vena cava. The hemodynamic profile during clamping and declamping the abdominal aorta was similar in both groups. CONCLUSIONS: Our findings suggest that pre-treatment with coenzyme Q10 may play a protective role during routine vascular procedures requiring abdominal aortic cross clamping by attenuating the degree of peroxidative damage.

Aortic Aneurysm, Abdominal↗
PubMed1995

Experience with protocol biopsies after solitary pancreas transplantation.

The early detection of allograft rejection remains elusive after solitary pancreas transplantation (PTX). We have previously described a modified technique of cystoscopic transduodenal PTX biopsy using the Biopty gun under ultrasound guidance. During the last 2 years, we performed 24 solitary PTXs with prospective protocol biopsy monitoring as well as biopsies performed whenever clinically indicated. The study group included 17 pancreas transplants alone, 6 sequential pancreas after kidney transplants, and 1 sequential pancreas after liver transplant. Five patients received pancreas retransplants. A total of 92 cystoscopically directed core PTX biopsies were performed, including 50 protocol biopsies (mean 2.1 per patient). Protocol biopsies were performed at 1 month (19), 2 months (3), 3 months (20), 6 months (7), and 12 months (1) after PTX. Adequate PTX tissue for histopathologic examination was obtained in 49 cases (98%). Biopsy findings included no rejection (34), mild rejection (13), pancreatitis (1), and cytomegalovirus infection (1). Overall, 15 of the 49 evaluable biopsies (31%) had significant histopathologic findings. All but 1 of the cases of mild rejection were treated with bolus steroids. Eight of these patients subsequently developed recurrent biopsy-proven rejection within 2 months; 5 grafts were subsequently lost to rejection between 3 and 13 months after PTX. Three biopsy complications occurred: 1 hematoma, 1 pancreatitis, and 1 ileus. Patient survival is 96% and PTX graft survival (complete insulin independence) is 75% after a mean follow-up of 15 months. In the remaining 42 clinically indicated biopsies, 3 were insufficient, 8 showed no rejection, and 31 (79%) had rejection. In half of these cases, the rejection was graded as moderate to severe. In conclusion, prospective monitoring with protocol PTX biopsies may result in the earlier detection of allograft rejection and have a direct effect on improving results after solitary PTX.

Adolescent↗