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1.
Crit Rev Biotechnol ; 39(2): 157-172, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30396282

ABSTRACT

Metal nanoparticles and metal oxides nanoparticles (MNPs/MONPs) have been widely included in a great diversity of products and industrial applications and they are already a part of our everyday life. According to estimation studies, their production is expected to increase exponentially in the next few years. Consequently, soil has been suggested as the main sink of MNPs/MONPs once they are deliberately or accidentally released into the environment. The potential negative perturbations that may result on soil microbial communities and ecological processes are resulting in concerns. Several nano-toxicological studies of MNPs/MONPs, reported so far, have focused on aquatic organisms, animals, and soil invertebrates. However, during recent years, the studies have been oriented to understand the effects of MNPs/MONPs on microbial communities and their interaction with soil components. The studies have suggested that MNPs/MONPs are one of the most toxic type to soil biota, amongst different types of nanomaterials. This may threaten soil health and fertility, since microbial communities are known to support important biological processes and ecosystem services such as the nutrient cycling, whereby their protection against the environmental pollution is imperative. Therefore, in this review we summarize the actual knowledge available from the last five years (2013-2018) and gaps about the potential negative, positive or neutral effects produced on soil by different classes of MNPs/MONPs. A particular emphasis has been placed on the associated soil microorganisms and biological processes. Finally, perspectives about future research are discussed.


Subject(s)
Metal Nanoparticles , Metals , Oxides , Soil Microbiology , Soil Pollutants , Metal Nanoparticles/chemistry , Metal Nanoparticles/toxicity , Metals/chemistry , Metals/toxicity , Microbiota , Nanotechnology , Oxides/chemistry , Oxides/toxicity , Soil/chemistry , Soil Pollutants/chemistry , Soil Pollutants/toxicity
2.
Int J Colorectal Dis ; 28(11): 1523-9, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23877264

ABSTRACT

PURPOSE: The lymph node status is one of the strongest prognostic determinants in rectal cancers. After chemoradiotherapy (CRT), lymph nodes are difficult to detect. This study aims to evaluate the feasibility of lymph node mapping in the mesorectum after CRT to analyze the pattern of metastasis spread and to assess the reliability of blue dye injection in sentinel lymph node detection. METHOD: Ten patients with cN+ mid/low RCs after CRT were prospectively enrolled. The protocol scheduled intraoperative blue dye injection, surgery, and specimen examination with fat clearance technique. The mesorectum was divided into three equal "levels" (upper, middle, and lower); each level was divided into three equal "sectors" (right anterolateral, posterior, and left anterolateral). Lymph nodes were defined "small" if ≤5 mm. RESULTS: Two hundred seventy-six lymph nodes were retrieved in ten patients; 76.5 % were small lymph nodes. Six patients were pN+ (33 metastatic lymph nodes, 76 % small); small lymph node analysis upstaged one patient from N0 to N1 and four patients from N1 to N2. Metastasis distribution across sectors was continuous, without "skip sectors." The blue dye detected the sentinel lymph node in all patients; in half of the cases, it was out of the tumor sector. Blue dye identified 69.7 % of metastatic lymph nodes; its sensitivity decreased together with the metastatic deposit size (84 % macrometastases, 28.6 % micrometastases, 0 % occult tumor cells; p = 0.004). CONCLUSION: The fat clearance technique should be the standard pathological examination in patients with RCs after CRT; N staging was improved by small lymph node identification. Lymph node metastases have a continuous spread through mesorectal sectors. Blue dye injection is effective in sentinel lymph node detection.


Subject(s)
Chemoradiotherapy , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Neoadjuvant Therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Aged , Aged, 80 and over , Humans , Intraoperative Care , Male , Middle Aged , Neoplasm Staging , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy
3.
Pancreas ; 22(4): 378-82, 2001 May.
Article in English | MEDLINE | ID: mdl-11345138

ABSTRACT

OBJECTIVE: To evaluate the short and long-term results of surgical treatment of calcifying chronic pancreatitis in our center. PATIENTS AND METHODS: We studied 55 consecutive patients operated on for chronic calcifying pancreatitis during a period of 12 years. The mean follow-up period was 6.2 years. Main outcome measures were operative mortality and morbidity, degree of pain control, diabetes onset, survival, and causes of death. RESULTS: The etiology was alcoholic in 48 patients and idiopathic in seven patients. A resection was performed in 78% of cases and a by-pass procedure was performed in 22%. Operative mortality was 3.6%; morbidity was 21.8%. A ductal adenocarcinoma was found in 3.6% of cases. The alcohol withdrawal rate was 78%. Complete pain control was achieved in 71.4% of the patients. Among diabetes, cirrhosis, type of surgery, smoking and alcohol abuse history, only alcohol withdrawal was associated with pain control (p < 0.03). A late reintervention was needed in only one patient in the by-pass group. Five and 10-year survival rates for the entire population were 80% and 61%, respectively. Among alcohol, cirrhosis, diabetes, and type of surgery, only the former was associated with survival (p < 0.003). Five-year actuarial survival was 55.6% for patients who continued drinking compared with 86.3% for ex-alcoholics. CONCLUSIONS: Surgical resection should be performed when required by the anatomical conditions because it was associated with good long-term pain control and low postoperative and late morbidity. Alcohol withdrawal has a key role for effective control of pain and prolonged survival.


Subject(s)
Calcinosis/complications , Calcinosis/surgery , Pancreatitis/complications , Pancreatitis/surgery , Treatment Outcome , Adult , Aged , Aged, 80 and over , Alcohol Drinking , Analgesia , Calcinosis/mortality , Chronic Disease , Diabetes Complications , Female , Humans , Male , Middle Aged , Pancreatitis/mortality , Pancreatitis, Alcoholic/complications , Pancreatitis, Alcoholic/mortality , Pancreatitis, Alcoholic/surgery , Postoperative Complications , Reoperation , Smoking , Survival Rate
4.
Am J Hypertens ; 10(9 Pt 1): 1058-63, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9324114

ABSTRACT

We explored the putative inhibitory effects of losartan, a potent nonpeptide, AT1 receptor antagonist, against thromboxane A2 (TxA2)/prostanoid (TP) receptor-mediated transcapillary shift of plasma fluid and proteins. The effects of the TP receptor agonist U-46619 (1.25 or 10 microg/kg intravenously) on hematocrit (Hct), albumin extravasation (AE), and mean arterial pressure (MAP) were evaluated in anesthetized Sprague-Dawley rats. U-46619 dose-dependently increased Hct (by 4.5% +/- 0.7% and 7.5% +/- 1.0% at the low and high dose, respectively; both P < .05 v vehicle-infused group) and decreased MAP (by 7.9% +/- 4.1% and 16.8% +/- 5.7% at the low and high dose, respectively; P = NS and P < .05 v vehicle-infused group, respectively). In these experiments, using a quantitative Evans blue technique, we showed that U-46619 dose-dependently increased AE in kidney, lung, spleen, and testis (by approximately 31%, 172%, 52%, and 57% at the highest dose) but not in adipose tissue, brain, liver, mesentery, and skeletal muscle. In the heart, AE was maximally increased by the low dose of U-46619. The U-46619 (10 microg/kg)-induced increases in Hct and AE and decreases in MAP were blocked by pretreatment with the TP receptor antagonist SQ 29,548 (2.5 mg/kg intravenously + 2.5 mg/kg/h) and the high dose of losartan (40 mg/kg intravenously). The low dose of losartan (10 mg/kg intravenously) did not significantly alter the responses to U-46619 except for the AE, which was reduced in some but not all tissues. Furthermore, the U-46619-induced changes in Hct (+6.3% +/- 1.7%), MAP (-13.9% +/- 8.4%) and AE were not affected in rats pretreated with the converting-enzyme inhibitor enalapril. Thus, selective activation of TP receptors by U-46619 induced plasma fluid and protein exudation; these responses were specifically attenuated by the relatively high dose of losartan, suggesting that this compound acts as a TP receptor antagonist in this experimental model.


Subject(s)
Capillary Permeability/drug effects , Capillary Permeability/physiology , Losartan/pharmacology , Prostaglandins/metabolism , Receptors, Cell Surface/physiology , Receptors, Thromboxane/physiology , 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Blood Pressure/drug effects , Bridged Bicyclo Compounds, Heterocyclic , Enalapril/pharmacology , Fatty Acids, Unsaturated , Hematocrit , Hydrazines/pharmacology , Male , Microcirculation/drug effects , Plasma Volume/drug effects , Rats , Rats, Sprague-Dawley , Serum Albumin/metabolism , Vasoconstrictor Agents/pharmacology
5.
J Pharmacol Exp Ther ; 280(2): 761-9, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9023289

ABSTRACT

Experiments performed in 226 pentobarbitone-anesthetized rabbits were designed to investigate the involvement of thromboxane/prostanoid and 5-hydroxytryptamine (5-HT)2A/C receptors during arterial thrombus formation in distinct low- and high-shear rate thrombosis models. Antithrombotic activities of the thromboxane/prostanoid receptor antagonist SQ 29,548 and two chemically distinct 5-HT2A/C receptor antagonists, ritanserin and ketanserin, were assessed first in low-shear rate (approximately 600 sec(-1)) arterial thrombosis, produced by insertion of a silk thread as thrombogenic substrate into the central section of an extracorporeal arteriovenous shunt established between the left carotid artery and the right jugular vein (n = 77), and second in high-shear rate (approximately 40,000 sec(-1)) arterial thrombosis, produced by critical stenosis and local endothelial injury of a carotid artery, characterized by cyclic flow reductions (CFRs) due to recurrent platelet aggregation and subsequent dislodgement of the thrombus (n = 149). Under low shear rate, SQ 29,548 (10-2500 microg/kg plus 10-2500 microg/kg/hr i.v.), but not ritanserin or ketanserin (both at 2500 microg/kg i.v.), dose-dependently inhibited thrombus formation. In contrast, under high shear rate, SQ 29,548 (10-160 microg/kg plus 10-160 microg/kg/hr i.v.) and both ritanserin and ketanserin (both at 10-2500 microg/kg i.v.) dose-dependently reduced CFR frequency, with ID50 values of 35 microg/kg (95% confidence limits, 24-58 microg/kg), 77 microg/kg (95% confidence limits, 40-132 microg/kg) and 89 microg/kg (95% confidence limits, 36-285 microg/kg) i.v., respectively. Furthermore, local infusion of the stable thromboxane A2 analog U-46619 (0.63 microg/kg/min) or 5-HT (20.8 microg/kg/min) proximal to the site of injury and stenosis in rabbits pretreated with either SQ 29,548 (40 microg/kg plus 40 microg/kg/hr i.v.) or ritanserin (160 microg/kg i.v.), respectively, restored CFR frequency to vehicle group levels in animals whose CFR frequency was previously reduced. The inhibitory activity of ketanserin and ritanserin on CFRs could not be attributed to 5-HT1B/D or alpha-1 adrenoceptor antagonist properties or to any hypotensive activity. These results provide firm evidence that thromboxane/prostanoid receptors are involved in arterial thrombosis in rabbits independently of the shear rate, whereas 5-HT2A/C receptors play a major role only in high-shear rate thrombus formation.


Subject(s)
Carotid Stenosis/physiopathology , Hemodynamics/drug effects , Hydrazines/pharmacology , Receptors, Prostaglandin/physiology , Receptors, Serotonin/physiology , Receptors, Thromboxane/physiology , Animals , Arteriovenous Shunt, Surgical , Aspirin/pharmacology , Blood Pressure/drug effects , Bridged Bicyclo Compounds, Heterocyclic , Carotid Arteries/pathology , Carotid Arteries/physiopathology , Carotid Arteries/surgery , Carotid Stenosis/pathology , Endothelium, Vascular/drug effects , Endothelium, Vascular/pathology , Endothelium, Vascular/physiopathology , Fatty Acids, Unsaturated , Heart Rate/drug effects , Jugular Veins/surgery , Ketanserin/pharmacology , Male , Oxadiazoles/pharmacology , Piperazines/pharmacology , Platelet Aggregation , Prazosin/pharmacology , Rabbits , Receptor, Serotonin, 5-HT2A , Receptor, Serotonin, 5-HT2C , Ritanserin/pharmacology , Serotonin Antagonists/pharmacology , Stress, Mechanical
6.
Naunyn Schmiedebergs Arch Pharmacol ; 356(4): 462-6, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9349632

ABSTRACT

We sought to determine whether the intrinsic pulmonary hypertensive activity of the purported thromboxane A2/prostanoid (TP) receptor antagonist, daltroban, was mediated by TP receptors, using the high efficacy TP receptor agonist, U-46619, and the silent TP receptor antagonist, SQ 29,548. In pentobarbitone-anesthetized, open-chest rats (n = 4-10 per group), non-cumulative injections of U-46619, dose-dependently increased mean pulmonary arterial pressure (MPAP) with an ED50 (geometric mean with 95% confidence limits in parentheses) of 1.4 (1.1-2.3) microg/kg i.v.. Daltroban increased MPAP in a bell-shaped manner, with an apparent ED50 [29 (21-35) microg/kg i.v.] being 21 fold less potent than that of U-46619. The maximal pulmonary hypertensive responses evoked by daltroban represented about half those induced by U-46619 (25.4+/-1.0 vs. 12.7+/-2 mmHg; P < 0.05 between groups). The TP receptor antagonist SQ 29,548 fully antagonized increases in MPAP evoked by equihypertensive doses of U-46619 (1.25 microg/kg) or daltroban (80 microg/kg). Further experiments were carried out to determine whether daltroban antagonized the pulmonary hypertensive responses evoked by the high efficacy agonist, U-46619, or by itself as receptor theory would predict for a partial agonist. Daltroban (10-2500 microg/kg) antagonized, although not fully, U-46619 (20 microg/kg)-evoked pulmonary hypertensive responses, since prominent intrinsic pulmonary hypertensive effects of daltroban were observed in the same range of doses. Furthermore, in contrast to U-46619 (1.25 microg/kg), daltroban (80 microg/kg) failed to evoke a second pulmonary hypertensive response following a previous injection, as would be expected for a partial agonist. Collectively, the results strongly suggest that daltroban behaves as a partial agonist at TP receptors in the pulmonary vascular bed of the rat in vivo.


Subject(s)
Phenylacetates/pharmacology , Receptors, Thromboxane/agonists , Sulfonamides/pharmacology , 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/antagonists & inhibitors , 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology , Animals , Blood Pressure/drug effects , Bridged Bicyclo Compounds, Heterocyclic , Fatty Acids, Unsaturated , Hydrazines/pharmacology , Hypertension, Pulmonary/chemically induced , Hypertension, Pulmonary/physiopathology , Male , Phenylacetates/antagonists & inhibitors , Rats , Sulfonamides/antagonists & inhibitors , Thromboxane A2/antagonists & inhibitors
7.
Scand J Gastroenterol ; 31(9): 917-20, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8888441

ABSTRACT

BACKGROUND: More than 100 different mutations in the adenomatous polyposis coli (APC) gene have been identified; virtually all lead to the production of a truncated protein. Clinical details of patients with missense mutations undoubtedly cosegregating with the disease have not been reported and may be relevant in understanding the APC protein function. METHODS: In one family with familial adenomatous polyposis (FAP) the APC gene was analyzed by SSCP and sequencing of the aberrant SSCP band. RESULTS: A missense mutation in exon 15 at nucleotide 4921 segregating with the disease was observed. This predicts a tryptophan instead of an arginine at amino acid 1641 of the APC protein. No such mutation was present in 100 control subjects. CONCLUSIONS: In this family the colonic manifestations are as expected for classical FAP. However, the occurrence of congenital hypertrophy of the retinal pigment epithelium is unusual, owing to the inconsistency of this manifestation between family members and because congenital hypertrophy of the retinal pigment epithelium is generally absent when mutations are after codon 1387.


Subject(s)
Adenomatous Polyposis Coli/genetics , Mutation , Adenomatous Polyposis Coli/pathology , Adenomatous Polyposis Coli Protein , Adult , Colon/pathology , Cytoskeletal Proteins/genetics , Exons , Female , Humans , Hypertrophy , Male , Middle Aged , Pigment Epithelium of Eye/pathology , Tryptophan/genetics
8.
Minerva Gastroenterol Dietol ; 41(2): 135-42, 1995 Jun.
Article in Italian | MEDLINE | ID: mdl-7647135

ABSTRACT

Surgery does not cure Crohn's disease, but only its complications, as the recurrence rate that requires a new intervention is 6% per year. The resections performed by the surgeon should be as limited as possible, in order to avoid the consequent malabsorption. The identification of two forms of Crohn's disease, with different aggressiveness, has found that the stricturoplastic is an encouraging way of treatment for those forms with a prevalent stenotic component. A lot of studies have evaluated the relationships between recurrences and resections on margins microscopically free or affected by the disease. The aim of this study was a retrospective verification of the influence of any possible microscopical residue of the disease on the recurrence rate, evaluating whether the two different forms of aggressiveness of the disease (presence of stenosis or fistula) can influence the rate and precocity of the recurrence onset. In 37 patients operated for the first time of ileal or ileocolic resection, the overall recurrence rate was 18.9%; neither the presence of microscopically affected margins nor the presence of fistulas or stenosis has showed to have an influence on the onset of the recurrences. The only data that emerged is a greater precocity of the onset of recurrence in those patients whose disease was characterised by the presence of enteric fistulas. The forms in which fistulas and perforations were evident showed a recurrence rate not significantly higher than that of forms with stenosis only, but the period of time free from the disease was notably longer for the latter. In the end, patients in which typical granulomas were present showed a recurrence rate of just 9%, compared to 23% of patients in which granulomas were absent. MATERIALS AND METHODS. From 1980 through 1992, 61 patients affected by Crohn's disease were operated. There were 39 men and 22 women (mean age: 40.4 years). The mean length of the follow-up was 55.5 months. It was the first operation for 43 patients, while 9 had already undergone surgery in other hospitals; 9 patients showed anorectal complications. The operations performed on the patients for the first time have been ileal resection in the following localizations: duodenum-jejunum 4, jejunum and ileal 34, colic 5; the recurrences treated have been ileal-jejunum in 7 cases and colic in 2. In 2 cases of recurrence a stricturoplastic has been performed. RESULTS. The operative mortality was of 3 patients: 2 due to sepsis for anastomotic dehiscence and 1 to systemic mycosis. Four postoperative fistulas were observed. Recurrence of the disease occurred in 13 patients (26.5%), specifically in 21.4% of the patients operated for the first time and in 57.1% of those that were operated for recurrences. DISCUSSION AND CONCLUSIONS. In the treatment of Crohn's disease, it is important to identify any possible group with high risk of recurrence in order to undertake an appropriate medical prophylaxis. The results concerning the presence of microscopical disease on the resection margins are today still controversial. Some groups of authors prefer wide resection margins, some others are in favour of restricted resections. Our considerations let us assert that in those patients in which the resections have been performed on margins with microscopic presence of the disease, the interval before the recurrence occurs is not significantly shorter than that of patients with free margins. But the patients suffering from Crohn's disease with fistulae, probably need medical post-operative therapy to delay recurrences onset.


Subject(s)
Crohn Disease/surgery , Adolescent , Adult , Aged , Colitis/surgery , Female , Follow-Up Studies , Humans , Ileitis/surgery , Male , Middle Aged , Prognosis , Recurrence , Retrospective Studies , Risk Factors , Time Factors
9.
Br J Pharmacol ; 115(1): 210-6, 1995 May.
Article in English | MEDLINE | ID: mdl-7647979

ABSTRACT

1. We evaluated the effects of daltroban on (i) human platelet shape change and aggregation in vitro, and (ii) mean systemic and pulmonary arterial pressures (MAP and MPAP, respectively) as well as haematocrit, in anaesthetized, open-chest Sprague-Dawley rats, compared with those of a chemically distinct prostanoid thromboxane A2 (TxA2) receptor antagonist, SQ 29,548, and agonist, U-46619. 2. In human platelets in vitro, daltroban (10 nM-100 microM; n = 6 per group) concentration-dependently induced shape change, attaining at 50 microM, a maximum amplitude of 0.83 +/- 0.09 mV representing 46.4 +/- 4.8% of that evoked by U-46619 (1.78 +/- 0.20 mV at 0.2 microM; n = 9); and inhibited U-46619-induced platelet aggregation with an IC50 of 77 (41-161)nM. SQ 29,548 (10 nM-100 microM; n = 6 per group) failed to evoke any platelet shape change, but potently inhibited U-46619-induced platelet aggregation with an IC50 < 10 nM. 3. In anaesthetized rats in vivo, daltroban (10-2500 micrograms kg-1, i.v. infused over 2 min; n = 4-8 per group) produced a bell-shaped dose-response curve for MPAP and haematocrit, and evoked maximal increases of 12.7 +/- 2.1 mmHg and 5.8 +/- 1.5% at 80 micrograms kg-1 (n = 6) and 630 micrograms kg-1 (n = 8), respectively (both P < 0.05) with ED50s of 20 (16-29) and 217 (129-331) micrograms kg-1, respectively. By comparison, U-46619(0.16-20 microg kg-1, i.v.), induced dose-dependent increases in MPAP and haematocrit (25.4 +/- 1.0 mmHg and 16.1 +/- 2.9% at the highest dose; n = 12, both P<0.01), with ED50s of 1.8 (1.3-2.5) and 3.9(3.5- 5.4) microg kg- 1, respectively. Daltroban dose-dependently increased MAP with a maximum amplitude of 42.2 +/- 4.4 mmHg at a dose of 80 microg kg-1 [ED50 = 94 (64-125) microg kg-1], similar to that induced by U-46619 (41.3 +/- 9.6 mmHg) at a dose of 0.63 microg kg-1 [ED50= 0.22 (0.13-0.24) microg kg-1]. SQ 29,548(10-2500 microg kg-1, i.v.; n =4 per group) failed to modify significantly any of these parameters.4. Our results clearly demonstrate that daltroban, in a similar manner to the TxA2 analogue, U-46619,but unlike the TxA2 receptor antagonist, SQ 29,548, exhibits significant intrinsic activity in human platelets in vitro and in the rat vasculature in vivo, possibly through TxA2 receptor activation.


Subject(s)
Blood Platelets/drug effects , Blood Pressure/drug effects , Phenylacetates/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation/drug effects , Sulfonamides/pharmacology , Thromboxanes/antagonists & inhibitors , 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid , Animals , Blood Platelets/physiology , Bridged Bicyclo Compounds, Heterocyclic , Dose-Response Relationship, Drug , Fatty Acids, Unsaturated , Hematocrit , Humans , Hydrazines/pharmacology , In Vitro Techniques , Male , Prostaglandin Endoperoxides, Synthetic/pharmacology , Rats , Rats, Sprague-Dawley , Thromboxane A2/analogs & derivatives , Thromboxane A2/pharmacology
10.
Am J Physiol ; 268(2 Pt 2): R366-74, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7864230

ABSTRACT

We investigated whether the stable thromboxane A2 (TxA2) analogue U-46619 had any direct effect on extracellular fluid partition. In anesthetized open-chest rats, U-46619 (1.25 and 20 micrograms/kg iv) dose dependently increased mean pulmonary arterial pressure and hematocrit, whereas mean systemic arterial pressure was raised only at the low dose of agonist. The increase in hematocrit (13.2 +/- 2.9% at 20 micrograms/kg; P < 0.05) still occurred in bilaterally nephrectomized rats and in binephrectomized plus splenectomized rats (11.6 +/- 2.7 and 12.2 +/- 4.6%, respectively; both P = NS vs. U-46619 in control rats), corresponding to a calculated decrease in plasma volume of 22.1 +/- 4.5, 19.6 +/- 4.0, and 19.2 +/- 5.8%, respectively. Plasma protein concentration increased less than hematocrit, and the coefficient of reflection was significantly lower in these groups, suggesting protein extravasation. Additional experiments showed that U-46619 (1.25 and 10 micrograms/kg iv) dose dependently increased the vascular leak of albumin mainly in lung, kidneys, and spleen but not in brain, liver, mesentery, and cardiac and skeletal muscles. Pretreatment with the TxA2 receptor antagonist SQ-29,548 (2.5 mg/kg iv bolus plus 2.5 mg.kg-1.h-1 as maintenance) abolished all effects of U-46619, including the increase in mean pulmonary arterial pressure, hematocrit, plasma protein concentration, and albumin extravasation and the decrease in mean systemic arterial pressure, plasma volume, and coefficient of reflection.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Capillary Permeability , Thromboxane A2/metabolism , 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid , Animals , Blood Proteins/metabolism , Bridged Bicyclo Compounds, Heterocyclic , Fatty Acids, Unsaturated , Hematocrit , Hemodynamics/drug effects , Hydrazines/pharmacology , Male , Microcirculation , Nephrectomy , Osmolar Concentration , Prostaglandin Endoperoxides, Synthetic/pharmacology , Pulmonary Circulation/drug effects , Rats , Rats, Sprague-Dawley , Receptors, Thromboxane/antagonists & inhibitors , Serum Albumin/metabolism , Splenectomy , Thromboxane A2/analogs & derivatives , Thromboxane A2/pharmacology
11.
Arch Mal Coeur Vaiss ; 87(8): 971-4, 1994 Aug.
Article in French | MEDLINE | ID: mdl-7755474

ABSTRACT

We investigated the possibility that the selective angiotensin II type 1 (AT1) receptor antagonist, losartan, interacts with thromboxane A2/endoperoxide (TxA2/PGH2) receptors. We measured changes in mean pulmonary arterial pressure (MPAP) induced by the stable TxA2 analogue, U-46619, during blockade of either TxA2/PGH2 or AT1 receptors, in anesthetized, open chest rats (n = 4-8 per group). U-46619 (1.25 and 10 micrograms/kg) dose-dependently increased MPAP. The U-46619 (1.25 micrograms/kg)-evoked increase in MPAP (approximately 51%; p < 0.01) was dose-dependently inhibited by the TxA2/PGH2 receptor antagonist, SQ 29,548 (approximately 94 and 102% at 0.63 and 2.5 mg/kg, respectively; both p < 0.05). Losartan also dose-dependently reduced this increase (approximately 11 and 65% at 2.5 and 10 mg/kg, respectively; p = NS and p < 0.05, respectively). Furthermore, losartan dose-dependently prevented the increase in MPAP (approximately 112%) induced by an 8 fold higher dose of U-46619 (10 micrograms/kg) by approximately 9 and 75% at doses of 10 and 40 mg/kg, respectively; p = NS and p < 0.05, respectively. Thus, selective activation of TxA2/PGH2 receptors by the TxA2 analogue, U-46619, induced pulmonary hypertension, which was specifically inhibited by the TxA2/PGH2 receptor antagonist, SQ 29,548 and the AT1 receptor antagonist, losartan, suggesting that the latter compound exerts antagonist activity at TxA2/PGH2 receptors.


Subject(s)
Angiotensin II/antagonists & inhibitors , Antihypertensive Agents/therapeutic use , Biphenyl Compounds/therapeutic use , Hypertension, Pulmonary/prevention & control , Imidazoles/therapeutic use , Tetrazoles/therapeutic use , Thromboxane A2/analogs & derivatives , 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid , Angiotensin II/therapeutic use , Animals , Biphenyl Compounds/pharmacology , Hypertension, Pulmonary/chemically induced , Imidazoles/pharmacology , Losartan , Prostaglandin Endoperoxides, Synthetic/adverse effects , Rats , Rats, Sprague-Dawley , Tetrazoles/pharmacology , Thromboxane A2/adverse effects , Vasoconstrictor Agents/adverse effects
12.
J Pharmacol Exp Ther ; 268(2): 747-52, 1994 Feb.
Article in English | MEDLINE | ID: mdl-8113986

ABSTRACT

Losartan is a potent, nonpeptide, angiotensin II type 1 receptor antagonist. We investigated the possibility that losartan may interact with thromboxane A2 (TxA2)/prostaglandin H2 (PGH2) receptors. We measured changes in mean systemic (MS) and pulmonary (MP) arterial pressures (AP) as well as in hematocrit induced by the TxA2 analog, U-46619 (9, 11-dideoxy-9 alpha, 11 alpha-methanoepoxy PGF2 alpha, during pharmacological blockade of either TxA2/PGH2 receptors or the renin-angiotensin system. In anesthetized, open chest rats, U-46619 dose dependently increased MPAP whereas MSAP presented a biphasic evolution. The U-446619 (1.25 micrograms/kg)-increased MPAP (52.4 +/- 12.1%; P < .005) was dose dependently inhibited by the TxA2/PGH2 receptor antagonist, SQ 29,548 ([1S-[1 alpha,2 alpha (5z),3 alpha, 4 alpha]]-7- [3-[[2-[(phenylamino)-carbonyl)hydrazino]methyl]-7-oxabiacyclo [2.2.1]hept-2-yl]-5-heptenoic acid) (10.6 +/- 2 and 2.1 +/- 1.4% at 0.63 and 2.5 mg/kg, respectively; both P < .05 vs. U-46619 in control rats). Losartan dose dependently reduced this increase (45.5 +/- 5.8 and 11.9 +/- 1.8% at 2.5 and 10 mg/kg, respectively; P = N.S. and P < .05 vs. U-46619 in control rats) whereas chronic suppression of angiotensin II generation by the converting-enzyme inhibitor enalapril (10 mg/kg/day per os for 4-5 days) did not affect this response. None of these treatments significantly reduced the U-46619-associated increase in MSAP. Moreover, the angiotensin II-evoked increases in MSAP and MPAP were suppressed by pretreatment with losartan but not with SQ 29,548.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Angiotensin II/antagonists & inhibitors , Angiotensin Receptor Antagonists , Antihypertensive Agents/pharmacology , Biphenyl Compounds/pharmacology , Hypertension, Pulmonary/prevention & control , Imidazoles/pharmacology , Receptors, Thromboxane/physiology , Tetrazoles/pharmacology , 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid , Animals , Blood Pressure/drug effects , Bridged Bicyclo Compounds, Heterocyclic , Enalapril/pharmacology , Fatty Acids, Unsaturated , Hematocrit , Hydrazines/pharmacology , Hypertension, Pulmonary/etiology , Losartan , Male , Prostaglandin Endoperoxides, Synthetic/pharmacology , Rats , Rats, Sprague-Dawley , Thromboxane A2/analogs & derivatives , Thromboxane A2/pharmacology
13.
Eur J Pediatr ; 150(6): 413-5, 1991 Apr.
Article in English | MEDLINE | ID: mdl-2040350

ABSTRACT

This paper describes the percentile curves for red blood cell (RBC) count, Hb, mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) values of beta zero-thalassaemia heterozygotes during infancy, childhood and adolescence. Hb values were about 2 g/dl below those of normal controls with a progressive increase with age paralleling the normal developmental trend. The Hb increase with age was due to a progressive rise in the Hb content per cell, the number of RBC remaining nearly constant. MCV and MCH values also increased with age with a pattern parallel to normal control. Because of the high prevalence of alpha-thalassaemia in the Sardinian population, to which all the subjects investigated belong, the 3rd MCH-MCV percentile curves of normal overlap the 97th curve of beta-thalassaemia heterozygotes. The HbA2 levels, however, were always increased as compared to normal. These results confirm in children than screening for heterozygous beta-thalassaemia in populations with a high incidence of alpha and beta-thalassaemia by MCV-MCH determination may overlook a sizeable proportion of beta-thalassaemia carriers. The knowledge of the extent of variation of RBC indices of beta-thalassaemia heterozygotes during infancy, childhood and adolescence, is very useful for the evaluation of a child presenting with a mild microcytic anaemia.


Subject(s)
Erythrocyte Count , Erythrocyte Indices , Hemoglobins/analysis , Thalassemia/blood , Adolescent , Age Factors , Child , Child, Preschool , Female , Genetic Carrier Screening , Heterozygote , Humans , Infant , Italy , Male , Thalassemia/genetics
15.
Dis Colon Rectum ; 30(4): 267-72, 1987 Apr.
Article in English | MEDLINE | ID: mdl-3030677

ABSTRACT

A physiologic and metabolic assessment was carried out on eight patients six months after total proctocolectomy with ileal reservoir for ulcerative colitis and familial adenomatosis coli. All patients were continent and able to defecate spontaneously, stool frequency ranging from two to five per 24 hours. Anal sphincter resting pressures (35 +/- 14 mmHg) and squeeze pressures (88 +/- 24.2 mmHg) were similar to those of a healthy population, with the exception of one patient's complaint of nocturnal mucous leakage per anus. Biopsies of the ileal mucosa of the reservoirs showed a mild inflammation in seven patients; in one a subtotal villous atrophy (plus glandular pattern) was found. Anthropometric measurements, lymphocyte counts, hemoglobin, albumin, transferrin, iron, B12, and folate were normal in all. In the majority of patients there was no evidence of bacterial overgrowth. Vitamin B12 absorption was reduced slightly in only one patient. Lipid absorption (as judged by the 14C-Triolein breath test) was abnormal in three patients. Fecal clearance of alpha 1 antitrypsin as protein losses index was abnormal in three patients. Bile acid malabsorption was the most important ileal dysfunction observed in the patients.


Subject(s)
Adenomatous Polyposis Coli/surgery , Anal Canal/surgery , Colectomy , Colitis, Ulcerative/surgery , Ileum/surgery , Adenomatous Polyposis Coli/physiopathology , Adult , Anal Canal/physiopathology , Breath Tests , Colectomy/adverse effects , Colitis, Ulcerative/physiopathology , Defecation , Feces/analysis , Feces/microbiology , Female , Humans , Ileum/physiopathology , Intestinal Absorption , Male , Manometry , Middle Aged , Rectum/surgery , alpha 1-Antitrypsin/analysis
16.
Helv Paediatr Acta ; 38(3): 255-65, 1983 Aug.
Article in English | MEDLINE | ID: mdl-6618892

ABSTRACT

We report the results of a two-year non randomized prednisolone trial carried out in 18 thalassemia major patients with chronic active hepatitis and in 16 controls. We found a beneficial effect on the biochemical remission rate and on the extent of liver inflammation with no significant side effects and no overt reactivation of possible latent HBV infection at three-year follow-up. However, a more prolonged longitudinal study is necessary in order to evaluate whether steroid treatment can impede the evolution to cirrhosis without determining long-term consequences, depending on virus-host interactions such as liver cell carcinoma.


Subject(s)
Hepatitis, Chronic/drug therapy , Hepatitis, Viral, Human/drug therapy , Methylprednisolone/therapeutic use , Thalassemia/therapy , Blood Transfusion , Child , Child, Preschool , Hepatitis B Surface Antigens/analysis , Hepatitis, Chronic/complications , Hepatitis, Chronic/immunology , Hepatitis, Viral, Human/immunology , Humans , Liver/pathology , Thalassemia/complications
17.
Am J Pediatr Hematol Oncol ; 5(1): 73-7, 1983.
Article in English | MEDLINE | ID: mdl-6859457

ABSTRACT

In this study we evaluated the effect of 1-year, subcutaneous desferrioxamine daily infusion on iron balance in 23 thalassemia major children, aged 8-74 months, with transfusional iron accumulation less than 3.8 g at the outset of the trial. Statistical analysis showed a significant correlation between transfusional iron accumulation and percentage of transfusional iron eliminated. Confidence limits analysis of these data indicated that over 3.5 g of transfusional iron load, 95% of the patients may achieve balance. The appropriate time to begin desferrioxamine infusion, therefore, seems to be after about 30 transfusions of packed red blood cells when iron accumulation of approximately 3 g is reached. As we found a statistically significant correlation between transfusional iron eliminated and serum ferritin levels, the evaluation of serum ferritin alone can also predict when balance can be obtained.


Subject(s)
Deferoxamine/pharmacology , Iron/metabolism , Age Factors , Child, Preschool , Deferoxamine/administration & dosage , Dose-Response Relationship, Drug , Humans , Infant , Infusions, Parenteral , Iron/blood , Iron/urine , Thalassemia/blood , Thalassemia/metabolism
18.
Pediatr Res ; 15(11): 1443-6, 1981 Nov.
Article in English | MEDLINE | ID: mdl-7301464

ABSTRACT

The distribution of red blood cell G6PD phenotype was studied by means of the methemoglobin elution test in newborn (46) and adult (50) GdMediterranean heterozygous females and newborn (20) and adult (30) hemizygous males. Newborn heterozygotes had a statistically significant (P less than 0.0005) lower mean red blood cell G6PD enzymatic activity (3.23 +/- 1.04) than did normal newborns (8.78 +/- 1.91), whereas there was no significant difference (P greater than 0.30) from the mean of adult heterozygotes (2.93 +/- 0.86). Like adults, newborn heterozygous females showed: (1) a clear correlation (P less than 0.001) between the percentage of enzyme-deficient red blood cells and G6PD enzymatic activity; and (2) the expected two red blood cell population, i.e., one deficient and the other normal (mosaicism). However, in newborns, the distribution of the subjects according to G6PD-deficient red blood cell percentage (mean percent, 43.67) was significantly shifted (P less than 0.025) in favour of the normal phenotype, unlike adult heterozygotes, who showed a symmetrical distribution of G6PD positive and negative red blood cells (mean percent G6PD-deficient red blood cells, 53.27; P greater than 0.20). Newborn hemizygous males showed a consistent percentage (average, 8.28 +/- 2.2) of stained red blood cells due to the presence of young erythrocytes (pseudomosaicism) unlike the occasional stained cells (less than or equal to 5) seen in adults. The prevalence of hyperbilirubinemia in hemizygous males and heterozygous females was 10.22 and 2.2%, respectively, whereas in G6PD normal newborns it was 5.1%. The practical implication of this study is that the diagnosis at birth of the heterozygous state for G6PD deficiency of the Mediterranean type may be more difficult than in adults. Therefore, very sensitive methods, such as the methemoglobin elution test, should be carried out.


Subject(s)
Erythrocytes/enzymology , Glucosephosphate Dehydrogenase Deficiency/genetics , Glucosephosphate Dehydrogenase/blood , Heterozygote , Female , Glucosephosphate Dehydrogenase Deficiency/enzymology , Humans , Infant, Newborn , Jaundice, Neonatal/etiology , Male , Phenotype , Regression Analysis
19.
Eur J Pediatr ; 137(3): 267-71, 1981 Nov.
Article in English | MEDLINE | ID: mdl-7318837

ABSTRACT

This study on serum ferritin levels in urinary iron excretion after 12h subcutaneous infusion of desferrioxamine in 10 thalassemia intermedia patients shows that even nontransfusion-dependent patients may have positive iron balance resulting in iron overload from 5 years of age. However, the iron overload found in these patients appears to be much lower than in age matched patients with transfusion-dependent thalassemia major. Iron overload increases with advancing age, as shown by increasing serum ferritin levels and desferrioxamine-induced urinary iron elimination. After a six month trial of 12h continuous subcutaneous desferrioxamine administration there was a significant decline in serum ferritin levels. From this study it seems that iron chelation is indicated in thalassemia intermedia patients over 5 years of age in order to prevent iron accumulation. However, the appropriate treatment schedule should be tailored to the individual needs of each patients, established by close monitoring of serum ferritin levels and desferrioxamine-induced urinary iron elimination.


Subject(s)
Deferoxamine/therapeutic use , Thalassemia/drug therapy , Adolescent , Age Factors , Child , Child, Preschool , Female , Ferritins/blood , Humans , Infant , Iron/blood , Iron/urine , Male , Thalassemia/blood
20.
Acta Haematol ; 65(1): 32-9, 1981.
Article in English | MEDLINE | ID: mdl-6791435

ABSTRACT

The quantitative and/or qualitative distribution of liver iron was assessed in 81 transfusion-dependent thalassemia major patients with chronic liver disease (36 with chronic active hepatitis, 23 with chronic persistent hepatitis, 22 with siderosis). Viral marker studies showed only 3 cases with both HBsAg and anti-HBc positivity in the serum, while the others had anti-HBc and anti-HBs or only anti-HBs or no B viral markers. A significantly higher iron overload was found in chronic hepatitis, particularly chronic active hepatitis, than in siderosis. The increased iron overload may be due to less intensive chelation treatment, higher intestinal absorption secondary to lower mean Hb levels, and/or to liver inflammation-dependent iron deposition. The liver iron overload in turn amy facilitate the development or persistence of chronic progressive liver disease.


Subject(s)
Iron/metabolism , Liver/metabolism , Thalassemia/metabolism , Transfusion Reaction , Adolescent , Child , Child, Preschool , Chronic Disease , Female , Hepatitis/metabolism , Hepatitis B Surface Antigens/analysis , Humans , Liver Diseases/etiology , Liver Diseases/metabolism , Male , Siderosis/metabolism
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