PubMed Health⌕ Search

Biomedical subjects

M Morpurgo

Publications and source records attributed to M Morpurgo.

At least 19 recordsLinked to original sources
PubMed2005

Influence of synthesis and processing conditions on the release behavior and stability of sol-gel derived silica xerogels embedded with bioactive compounds.

The influence of processing parameters and synthetic strategies in the properties of sol-gel derived silica matrices intended for the release of bioactive compounds was investigated. The time-evolution of the matrix properties during its aging at room temperature in the dry and wet forms was investigated by measuring some of its physical and drug retaining properties. The results indicate that long term gel aging in the wet form is fundamental for the obtainment of dry matrices that are stable upon storage, a fundamental requirement for any practical application. In the case of hybrid matrices obtained by replacing part of the tetraethoxysilane precursor with mono-methyl trimethoxysilane, the order of addition of the reaction component is also important in determining the properties of the final dry gel, probably by influencing the polymer structural properties. This parameter acts synergistically with the matrix composition in determining the release properties of xerogels embedded with bioactive compounds.

Chemical Phenomena↗
PubMed2005

In vitro methods for the evaluation of drug availability from suppositories: comparison between biological and artificial membranes.

Drug availability from suppositories is currently evaluated in vitro by means of a model consisting of a dialysis tube (porous membrane) or isolated biological membrane (animal rectum). We propose a new alternative in vitro method to determine drug availability from suppositories consisting of an artificial membrane soaked with n-octanol, coupled with a filter paper sheet soaked with phosphate buffer. This method provides for an integrated hydro-lipophilic simulation of the biological membrane, including the mucus layer adhering to the rectal mucosa. By simply using the porous membrane, the amount of drug released varied directly according to its solubility for formulations with lipophilic excipients. For formulations with hydrophilic excipients, drugs with low/intermediate solubility in water showed increased availability in comparison to lipophilic excipients. The in vitro rat rectum model provided overall results that were similar to those obtained with the porous membrane method, although the percentage values of AUC were lower. The new model of in vitro simulated absorption produced a degree of drug availability that was lower in comparison to both previous methods. However, the simulated model appeared to give a pattern of drug availability closer to that of the model of in vitro rat rectum. The new in vitro artificial model thus appears to be useful in suppositories preformulation studies, allowing for an estimate of drug availability and the choice of the most adequate excipient.

Algorithms↗
PubMed2004

Silica xerogels as a delivery system for the controlled release of different molecular weight heparins.

In this work, we investigated a sol-gel derived silica matrix as a delivery system for the prolonged release of different molecular weight heparins, which allows the glycosaminoglicons to retain their whole biological activity. Several xerogels were obtained by embedding different molecular weight heparins into matrices prepared by using different amount of NH4OH as a catalyst during gel formation. Gel synthesis parameters, drug release properties, and xerogels surface area were evaluated. Unfractionated, low and oligo-molecular weight heparins were embedded into xerogels and the effect of the molecular weight on the release kinetics and the retained biological activity has been investigated. The results show that the surface area of the matrix is a determinant parameter affecting drug release kinetics. This structural feature can be modified by varying the catalyst tetraethoxysilane molar ratio used during the matrix synthesis. In most cases release kinetics fitted the Higuchi diffusive model and a lower diffusion rate was observed from silica matrices characterized by a smaller surface area. In the case of matrices with lower surface area, loaded with unfractionated heparin, zero order kinetics was observed. In this paper, we have defined a heparin release silica xerogel system and we have pointed out how modulation of its synthesis parameters allows adjusting the release of heparin according to therapeutic needs.

Anticoagulants↗
PubMed2001

[Pulmonary embolism: the past and . . . the future].

The history of pulmonary embolism cannot be reconstructed reliably beyond the last two centuries, starting with the Napoleon's times by the works of Laennec. We owe the first pathological and clinical descriptions to European scientists, especially French, German and Italian. Interestingly, some ideas regarding pathophysiology and even hemodynamics can be found in papers published as early as the end of the 19th century. Of note, the strong relationship between venous thrombosis and pulmonary embolism, suspected already in the middle of the 19th century, resulted later in a new clinical entity named venous thromboembolic disease. Only just before the second world war "modern" diagnostic tests entered into the clinical arena. Beginning with electrocardiography and X-ray techniques including pulmonary angiography, the progress in the field of imaging continued with lung scan, echocardiography, computed tomography, and finally still largely unexplored ultra-fast magnetic resonance imaging techniques: despite this technological development the correct diagnosis of pulmonary embolism in daily practice remains an important challenge. This is due to the lack of a single test which would combine high diagnostic power, round-the-clock availability and reasonably low cost. Though thrombotic origin of pulmonary embolism was well documented for almost two centuries, anticoagulation as a treatment for venous thromboembolism dates back much less than a century and thrombolysis was initiated only 30 years ago. What is even worse, those 30 years were not enough for us to identify clear-cut criteria in the selection between thrombolysis and anticoagulation in individual patients. Not to speak about the problem regarding optimal duration of secondary prophylaxis after a thromboembolic episode. Still how long shall we be debating about the same problems at the bed of our patients with venous thromboembolism? Or maybe the near future will bring completely new answers to our old questions? What type of case report related to pulmonary embolism will have the chance to be accepted for publication in the Italian Heart Journal in the year ... 2050? Future will show? But only if we help it....

Forecasting↗
PubMed2000

A labeling, detection, and purification system based on 4-hydroxyazobenzene-2-carboxylic acid: an extension of the avidin-biotin system.

We introduce a new nonradioactive, chromogenic label based on 4-hydroxyazobenzene-2-carboxylic acid (HABA), which is suitable for bioanalytical application, e.g., detection, localization, isolation, and purification. The HABA label is superior to other systems where it is difficult to separate labeled from unlabeled molecules or to determine the amount of label. HABA is readily detected spectroscopically by its absorption at 350 nm or by its interaction with avidin that results in a red shift to 500 nm. The HABA reagents described can be conjugated to a variety of functional groups on biomolecules and purified thereafter by affinity chromatography on an avidin column. The interaction of the HABAylated biomolecules with their corresponding targets is detected with high-affinity anti-HABA antibodies or with avidin. The nonradioactive, chromogenic HABA-based reagents form a homogeneous system that can complement or replace systems where facile quantification of the label is desired.

Antibodies↗
PubMed2000

[The cardiologist facing pulmonary embolism. The experience of 160 cases of acute cor pulmonale].

BACKGROUND: The results of recent multicenter studies dealing with pulmonary embolism often reveal remarkable discrepancies in terms of diagnosis, prognosis and treatment, partly due to the heterogeneity of study patients and of evaluation criteria. Our prospective study focused exclusively on patients affected by pulmonary embolism with a hemodynamic pattern of acute cor pulmonale, investigated at a single center. Particular attention was paid to in-hospital mortality, embolic recurrences, major bleeding and underlying pathologies. METHODS: This study includes 160 cases (103 women with a median age of 71 years and 57 men with a median age of 65 years) in whom the clinical and echocardiographic findings suggestive of acute pulmonary embolism were confirmed by lung perfusion scan, pulmonary angiography, techniques for the detection of deep vein thrombosis and/or autopsy. RESULTS: The most common clinical manifestations were: dyspnea (92% of cases), tachycardia (80%), syncope (44%), cardiac arrest (22%), and shock (20%). Thoracic pain was present in only 27% of patients. None of the patients showed a normal ECG; a right bundle branch block was found in 47% of cases. T-wave inversion in the precordial leads (32%) was not related to the severity and outcome of pulmonary embolism. Present or previous deep vein thrombosis was found in 53 and 26% of cases, respectively. Only in 2 patients pulmonary embolism was secondary to a deep vein thrombosis of the upper limbs. Intravenous heparin alone was used in 36% of cases, whereas 56% were treated with thrombolytic agents + heparin. Major bleeding occurred in 9% of patients treated with heparin alone, and in 16% of those who received heparin + thrombolytic drugs. Death occurred in 17% of the former, and in 27% of the latter patients. The in-hospital mortality rate was related not only to the presence of cardiac arrest and--to a lower degree--of shock, but also to the recurrence of pulmonary embolism and to the underlying heart disease. No relationship was found between mortality and age, intracardiac thrombi or malignancy. Prognosis was quite different depending on clinical presentation, with a death rate ranging from 11% in the absence of systemic hypertension, and 77% in the presence of cardiac arrest. CONCLUSIONS: Even the "massive" pulmonary embolism that is observed in a cardiac department represents a true "spectrum" of pathological conditions, a spectrum that should be taken into account not only in order to evaluate prognosis and treatment in a particular case, but also when meta-analyses are performed.

Acute Disease↗
PubMed1999

Bioconjugation in pharmaceutical chemistry.

Polymer conjugation is of increasing interest in pharmaceutical chemistry for delivering drugs of simple structure or complex compounds such peptides, enzymes and oligonucleotides. For long time drugs, mainly with antitumoral activity, have been coupled to natural or synthetic polymers with the purpose of increasing their blood permanence time, taking advantage of the increased mass that reduces kidney ultrafiltration. However only recently complex constructs were devised that exploit the 'enhanced permeability and retention' (EPR) effect for an efficient tumor targeting, the high molecular weight for adsorption or receptor mediated endocytosis and finally a lysosomotropic targeting, taking advantage of acid labile bonds or cathepsin susceptible polypeptide spacers between polymer and drug. New original, very active conjugates of this type, as those based on poly(hydroxyacrylate) polymers, are already in advanced state of development. Labile oligonucleotides, including antisense drugs, were also successfully coupled to polymers in view of an increased cell penetration and stabilization towards nucleases. However, the most active research activity resides in the field of polypeptides and proteins delivery, mainly for the two following reasons: first of all because a great number of therapeutically interesting compounds are now being produced by genetic engineering in large quantity and, secondly, because these products are difficult to administer to patients for several inherent drawbacks. Proteins are in fact easily digested by many endo- and exo-peptidases present in blood or in other body districts; most of them are immunogenic to some extent and, finally, they are rapidly excreted by kidney ultrafiltration. Covalent polymer conjugation at protein surface was demonstrated to reduce or eliminate these problems, since the bound polymer behaves like a shield hindering the approach of proteolytic enzymes, antibodies, or antigen processing cell. Furthermore, the increase of the molecular weight of the conjugate allows to overcome the kidney elimination threshold. Many successful results were already obtained in peptides and proteins, conjugated mainly to water soluble or amphiphilic polymers like poly(ethylene glycol) (PEG), dextrans, or styrenemaleic acid anhydride. Among the most successful are the conjugates of asparaginase, interleukin-2 or -6 and neocarcinostatin, to remind some antitumor agents, adenosine deaminase employed in a genetic desease treatment, superoxide dismutase as scavenger of toxic radicals, hemoglobin as oxygen carrier and urokinase and streptokinase as proteins with antithrombotic activity. In pharmaceutical chemistry the conjugation with polymers is also of great importance for synthetic applications since many enzymes without loss of catalytic activity become soluble in organic solvents where many drug precursors are. The various and often difficult chemical problems encountered in conjugation of so many different products prompted the development of many synthetic procedures, all characterized by high specificity and mild condition of reaction, now known as 'bioconjugation chemistry'. Bioconjugation developed also the design of new tailor-made polymers with the wanted molecular weight, shape, structure and with the functional groups needed for coupling at the wanted positions in the chain.

Animals↗
PubMed1999

N-hydroxysuccinimide carbonates and carbamates are useful reactive reagents for coupling ligands to lysines on proteins.

Ligands containing amino or hydroxyl groups were converted to their corresponding activated N-hydroxysuccinimidyl carbamate and carbonate by reaction with disuccinimidyl carbonate (DSC). The latter reagents can be used for the group-specific modification of primary amines as an alternative to the widespread usage of N-hydroxysuccinimide esters. Biotin and 2,4-dinitrophenyl (DNP) derivatives were used as examples to demonstrate the approach. Biotin and DNP were each extended by attaching two different spacer arms, carrying either a hydroxyl group or a primary amine as terminal functions. The latter were then activated via their conversion to N-hydroxysuccinimide carbonates and carbamates, respectively. The usefulness of these reagents for protein modification was investigated. The modified proteins obtained exhibited similar stability and activity characteristics compared to those modified with active N-hydroxysuccinimdyl esters. The activation of hydroxy- or amino-terminating compounds with DSC represents a general method that can be applied to any ligand which contains these functional groups for its covalent coupling to amines.

Avidin↗
PubMed1998

Factors influencing the clinical diagnosis of pulmonary embolism: analysis of 229 postmortem cases.

Although appreciable advances have been made in understanding epidemiology, diagnosis and treatment, acute pulmonary embolism (PE) is still largely undetected and untreated. The aim of our study was to ascertain whether the rate of correct clinical diagnosis of acute PE has changed in recent years (from 1989 to 1995) and, possibly, to identify factors that might contribute to the underdiagnosis of the disease.

Acute Disease↗
PubMed1998

[The traps of pulmonary embolism].

The clinical diagnosis of pulmonary embolism (PE), even massive, remains difficult and perplexing. In our hospital, the percentage of exact clinical diagnoses has not significantly changed over recent years, with a false-negative rate of 78%, and a false-positive rate of 2%. In approximately 20% of cases, autopsy showed several emboli and pulmonary infarctions of various ages, indicating recurrent embolic episodes. The diseases most frequently associated were cardiac diseases (51%) and tumours (24%). Pneumonia considerably decreases the probability of an exact diagnosis of PE; hospitalisation in the Cardiology department or Intensive Care Unit increased the probability of this diagnosis. While the numerous diagnostic algorithms recently proposed have a limited value, the process integrating clinical and instrumental data in order to establish a prospective clinical probability, should facilitate identification of acute PE in live patients.

Acute Disease↗
PubMed1997

Prevalence and prognostic significance of right-sided cardiac mobile thrombi in acute massive pulmonary embolism.

The prevalence of right-sided cardiac mobile thrombi, "in transit" from the systemic venous system, was 18% in a series of 130 patients with massive pulmonary embolism referred to early echocardiography and receiving thrombolytic drugs (56%) or intravenous heparin (40%). The mortality rate was lower than previously reported and seemed to be related more to clinical and hemodynamic impairment than to presence of thromboembolus.

Acute Disease↗
PubMed1997

Modulation of pulmonary arterial input impedance during transition from inspiration to expiration.

We investigated whether respiration influences pulmonary arterial input impedance during transition from inspiration to expiration in five anesthetized, spontaneously breathing dogs. Impedance (Z) was separately assessed for heart beats occurring in inspiration, in expiration, and during the transition from inspiration to expiration (transitional beat). Transitional beats were scored by the ratio between the fraction of beat falling in expiration and the total beat duration [expiratory fraction (Efr)] to quantify their position within the transition. In transitional beats, input resistance linearly increased with Efr; Z modulus at the heart-rate frequency (fHR) decreased up to -50% for Efr = 50%. Z phase at fHR was greater than in inspiration for Efr <40% and lower for Efr >50%. Unlike blood flow velocity, mean value and first harmonic of pulmonary arterial pressure were correlated to Efr and paralleled the changes of input resistance and Z at fHR. This indicates that respiration influences Z through modifications in arterial pressure. The evidence of important respiratory influences on Z function may help the pathophysiological interpretation of dysfunctions of the right heart pumping action, such as the so-called cor pulmonale.

Animals↗
PubMed1997

"False negatives" and "false positives" in acute pulmonary embolism: a clinical-postmortem comparison.

Although recent advances have been made in understanding its epidemiology, diagnosis and treatment, pulmonary embolism (PE) is still largely undetected and untreated, and the mortality rate has not appreciably changed in the last decades. The aim of this study was to: compare the postmortem frequency of massive and sub-massive PE during two different time periods in the same general hospital; ascertain whether the percentage of correct clinical diagnosis of PE has changed; identify factors which might contribute to the inaccuracy of the clinical diagnosis of PE. Altogether, 288 patients with autopsy-proven PE and adequate clinical data were collected in the first period; 182 subjects with the same characteristics were found in the second period. Cases observed from 1989 through 1994 were evaluated in terms of frequency of false negatives and false positives, predictive value of the clinical diagnosis of PE, and correlations between clinical and post-mortem diagnosis of PE on one side and several independent variables such as age, gender, associated diseases, recent surgery on the other. In our hospital the frequency of massive and submassive PE at autopsy was 8.6% from 1966 through 1974, 12.6% from 1989 through 1994 (p < 0.01). The percentage of correct clinical diagnosis of PE was 19.6% in the former period, 21.6% in the latter (NS) with 78.57% of false negatives and only 1.73% of false positives. Altogether the true positives were 21.42%, most of them being patients with massive PE. Clinical findings showed the coexistence of heart disease in 51.6% of the cases, congestive heart failure in 20.15%, metabolic disease in 7%, stroke in 12.5%, recent surgery in 12.5%. Autopsy revealed the presence of pulmonary infarction in 22% of cases, malignancy in 24.0%, pneumonia in 17.05%, acute myocardial infarction in 14.8%. Seventy percent of the cases in whom the point of origin of thromboemboli could be demonstrated had one or more thrombus in the district of inferior vena cava, more frequently at the level of the femoral and iliac veins. The positive predictive value of the clinical diagnosis of PE was 0.60, the negative predictive value 0.84. Multivariate logistic regression analysis showed that the clinical diagnosis of PE was hindered by the presence of pneumonia, facilitated by admission to the Cardiological Department. Age, duration of hospitalization, presence of pulmonary infarction, cancer, obesity, stroke, heart failure and recent surgery did not influence the clinical diagnosis of PE in this series. A positive correlation (p < 0.05) was found between autopsy rate and the percentage of correct clinical diagnosis of PE in the various hospital departments. This relationship needs further investigation, all the more so as in most countries the autopsy rate has been dramatically declining in recent times, especially in late life. In conclusion, at least in some institutions, the autopsy frequency of PE has increased during the last decades, and this increase has not been paralleled by a significant improvement in clinical diagnosis.

Acute Disease↗