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Biomedical subjects

G Cavallaro

Publications and source records attributed to G Cavallaro.

At least 19 recordsLinked to original sources

A new biodegradable and biocompatible hydrogel with polyaminoacid structure.

The preparation and physicochemical and biological characterization of a novel polyaminoacid hydrogel have been reported. The alpha,beta-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) has been used as a starting polymer for a derivatization reaction with methacrylic anhydride (MA) to give rise to the methacrylate derivative named PHM. Photocrosslinking of PHM has been performed in aqueous solution at 313 nm and in the absence of toxic initiators. PHM-based hydrogel has been characterized by scanning electron microscopy, X-ray diffractometry, swelling measurements in aqueous media; the degradation of PHM-based hydrogel has been evaluated as a function of time in the absence or in the presence of esterase. Besides, the biocompatibility of this hydrogel and of its degradation products has been evaluated by performing in vitro assays on human chronic myelogenous leukaemia cells (K-562), chosen as a model cell line. Finally, ATR-FTIR measurements have showed that interaction between PHM-based hydrogel and each of four plasma proteins (albumin, gamma-globulin, transferrin and fibrinogen) does not cause change in protein conformation thus supporting its potential use as a material to prepare parenteral drug delivery systems.

Biocompatible Materials↗

Giant GIST of the mesocolon: report of a case.

UNLABELLED: Gastrointestinal stromal tumors are rare neoplasms arising from mesenchymal cells of the gastrointestinal tract, that strongly express a class III receptor tyrosine kinase, called KIT, due to some mutations in the KIT proto-oncogene. Two thirds of GISTs are found in the stomach, 20% to 50% in the small bowel (one third in the duodenum), and 5% to 15% in colon and rectum; GISTs, however, may rarely be found also in the oesophagus, omentum, mesentery or the retroperitoneum. Their treatment is strictly surgical, and only R0 resection can achieve good RESULTS: Treatment with Imatinib seems to be promising in case of unresectable or metastatic GIST, even if some trials are studying its effects after curative resection. GIST of the mesocolon are rare, and as in the other locations, require extensive surgery. The Autohrs report a case of giant malignant GIST arising from transverse mesocolon, treated by en-bloc resection of the tumor with a segment of transverse colon and great omentum.

Aged↗

K(+) and Na(+) effects on the gelation properties of kappa-Carrageenan.

The effects of K(+), Na(+) ions and their mixture on the conformational transition and macroscopic gel properties of kappa-Carrageenan system have been studied using different experimental techniques. The macroscopic gelation properties of kappa-Carrageenan were found to be dependent upon cosolute type. Indeed, a more ordered and strong gel was obtained in the presence of K(+) with respect to Na(+) ions. The gel properties obtained using mixtures of two cosolutes are shown to depend on the [K(+)]/[Na(+)] ratio.

Carrageenan↗

Dual role of VEGF in pretreated experimental ePTFE arterial grafts.

BACKGROUND: Lack of endothelialization and abnormal smooth muscle cell (SMC) growth adversely affect the outcome of vascular synthetic grafts. The aims of our study were to investigate how a coating of extracellular matrix (ECM) and vascular endothelial growth factor (VEGF) might affect the endothelialization rate, smooth muscle cells (SMC) proliferation, and myointimal hyperplasia in experimental arterial ePTFE grafts. METHODS: In each of 30 male Lewis rats, a 1-cm-long ePTFE graft was inserted at the level of the abdominal aorta. Animals were randomized in five groups (six animals each): groups A and A1 received ePTFE grafts coated with a synthetic extracellular matrix (growth factor-reduced matrigel) containing VEGF; groups B and B1 received ePTFE grafts coated with synthetic ECM; and group C received ePTFE grafts alone. The grafts were explanted at 30 days from surgery for immunohistochemical analysis. RESULTS: Both endothelialization rate and myointimal hyperplasia were augmented in group A versus groups B and C, and these findings were statistically significant. SMC density resulted significantly higher in group A versus groups B and C, and this was associated with an altered expression of bFGF and TGFbeta. CONCLUSIONS: Pretreating ePTFE grafts with synthetic ECM and VEGF results in better endothelialization, but also in undesired higher SMC density and myointimal hyperplasia.

Animals↗

Synthesis, physico-chemical and biological characterization of a paclitaxel macromolecular prodrug.

Paclitaxel was attached to poly(hydroxyethylaspartamide) via a succinic spacer arm by a two-step protocol: (1) synthesis of 2'-O-succinyl-paclitaxel; (2) synthesis of PHEA-2'-O-succinyl-paclitaxel. The 2'-O-succinyl-paclitaxel derivative and the macromolecular conjugate were characterized by UV, IR, NMR and mass spectrometry analysis. The reaction yields were over 95% and the purity of products over 98%. Paclitaxel release and degradation from 2'-O-succinyl-paclitaxel occurred at a faster rate at pH 5.5 than 7.4. After 30 h of incubation at pH 5.5 and 7.4 the released free paclitaxel was about 40 and 20%, respectively. In plasma both drug release and degradation were found to occur at a higher rate than in buffer at pH 7.4 suggesting that an enzymatic mechanism could be involved. The paclitaxel release and degradation from PHEA-2'-O-succinyl-paclitaxel were negligible at pH 5.5 and 7.4 and very slow in plasma. Investigation carried out using murine myeloid cell line showed that the polymeric prodrug maintains partial pharmacological activity of paclitaxel. The DL50 of the conjugate (over 40 ng/ml) as compared to free paclitaxel (about 1 ng/ml) was correlated to the slow drug release. Finally a pharmacokinetic study carried out by intravenous inoculation of the macromolecular prodrug to mice demonstrated that the polymer conjugation modify dramatically the in vivo fate of the drug. The conjugate disappeared from the bloodstream much more quickly as compared to both free drug and naked polymer. Massive accumulation of bioconjugate in the liver (80% of the dose) was found to persist throughout 1 week.

Animals↗

Presurgical antimicrobial prophylaxis: effect on ocular flora in healthy patients.

OBJECTIVE: Evaluation of presurgical antimicrobial prophylaxis for reduction of ocular flora. SETTING: Ophthalmology Section, Department of Medicine and Surgery, University of Catania, Italy. METHODS: Three days before photorefractive keratectomy (PRK), conjunctiva of 70 healthy patients (100 eyes) were swabbed. After 3 days of instillation of ofloxacin 0.3% (3 times daily), conjunctival swabs were taken again. Bacteria were isolated and identified from each swab. RESULTS: A total of 191 independent isolates were obtained prior to antimicrobial treatment. Bacteria were isolated from all 100 eyes sampled. Gram-positive species predominated, with Staphylococcus epidermidis and Staphylococcus aureus cultured from 69% and 25% of eyes sampled, respectively. Species of the anaerobic genera Peptococcus and Peptostreptococcus were found in 22% and 14% of eyes, respectively. After prophylaxis with ofloxacin, bacteria could be cultured from only 7% of eyes (10 independent isolates). All isolates were sensitive to ofloxacin except 5 strains of S. epidermidis, which displayed intermediate sensitivity. No infections occurred after PRK. CONCLUSION: Prophylaxis by instillation of ofloxacin 0.3% 3 times daily for 3 days substantially reduced the ocular flora of 100 healthy eyes prior to refractive surgery.

Administration, Topical↗

Effects of zafirlukast on bronchial asthma and allergic rhinitis.

Asthma and allergic rhinitis are common conditions, occurring with increasing prevalence and frequently coexist. In both conditions histamine and cysteinil leukotrienes are important pathogenic inflammatory mediators. We evaluated the effects of the leukotriene receptor antagonist zafirlukast, 20mg administered twice daily for 2 weeks, in patients with allergic rhinitis and bronchial asthma during the grass pollen season. Patients underwent skin prick testing, spirometry, rhinomanometry, mucus transport test with saccharine, nasal epithelial brushing to study ciliary beat and, finally, nasal lavage.Thirty-five subjects completed the study. At the end of the study period, zafirlukast significantly reduced asthma and rhinitis symptoms (P< or =0.05); FEV(1) values were unchanged (P=0.10), whereas nasal resistances showed a decrease following treatment (P=0.01). Ciliary beat frequency (CBF) also improved (P=0.00), although mucociliary transport showed no improvement (P=0.87). The number of eosinophils in nasal lavage fluid decreased (P=0.00) while that of neutrophils was unchanged (P=0.09). These positive effects suggest that zafirlukast may be usefully employed in the treatment of both bronchial asthma, as previously demonstrated, and allergic rhinitis.

Adolescent↗

Clinical results and thoughts on sensory nerve repair by autologous vein graft in emergency hand reconstruction.

Lesions of the digital and other sensory nerves in the hand are common. Based on experimental studies on vein graft as a support for peripheral nerve regeneration, the Authors have been using a simple vein graft to bridge sensory nerve gaps when treating acute hand injuries. This is a retrospective study on the results of 22 sensory nerves repaired using vein grafts in cases in which primary suture was not feasible, in emergency hand reconstruction. Patients were informed that a secondary nerve graft could possibly be necessary in the future. Patients were reviewed by two independent observers at least one year after repair and evaluated using the Highest scale as modified by MacKinnon & Dellon. Evaluation chart included influence of repair on rehabilitation program and presence of painful neuromas and scars as well as patient satisfaction. Results were classified according to Sakellarides and 20/22 were classified as very good or good. Cases classified as poor were satisfied and no secondary nerve grafting has been carried out. Rehabilitation of the associated lesions (tendon lacerations or bone and soft tissue damage) was not influenced by the nerve repair and no painful neuroma was reported in the series. In conclusion, since the literature shows unsatisfactory results in repair of digital nerves with nerve grafts, since it's been demonstrated that an unrepaired sensory nerve leads to painful scar and painful neuroma and since we are reluctant to use nerve grafts in emergency procedures, we recommend this simple method because it is easy, low-cost and effective.

Adolescent↗

[Telangiectasias associated with reticular veins. Sclerotherapy or combined sclerotherapeutic and surgical approach?].

BACKGROUND: We compare the results obtained with sclerotherapy or combined surgical and sclerotherapic approach in two groups of patients, affected by reticular veins-related telangiectasias without incompetence of the saphenous systems or perforating veins. METHODS: 44 female patients were evaluated at our Institution. The first group (21 patients) was treated with sclerotherapy (polidocanol at a concentration of 1% for the reticular veins and 0.25% for the telangiectasias); the second group (23 patients) was treated with a combined approach (ambulatory phlebectomy according to Müller and sclerosis using polidocanol at a concentration of 0.25%). Six and twelve months after surgery or sclerotherapy, we evaluated the appearance of hyperpigmentation or telangiectatic matting, and the recurrence of the treated vessels. RESULTS: In the first group, the hyperpigmentations and the appearance of telangiectatic matting showed, after 6 months, an incidence rate of 14.3% after 12 months, a recurrence of the treated vessels was observed in 4 patients (19%). In the second group, the hyperpigmentations and the appearance of telangiectatic matting showed, after 6 months, an incidence rate of 4.3% at 12 month follow-up no recurrence of treated vessels was observed. CONCLUSIONS: The combined approach might be considered, in selected patients, a valid alternative to sclerotherapy in the treatment of reticular veins-related telangiectasias, particularly in preventing side effects such as hyperpigmentations and telangiectatic matting.

Adult↗

alpha,beta-poly(asparthylhydrazide)-glycidyltrimethylammonium chloride copolymers (PAHy-GTA): novel polymers with potential for DNA delivery.

Hydrophilic polycations form complexes when mixed with plasmids. Following functionalisation with glycidyltrimethylammonium chloride (GTA) alpha,beta-poly(asparthylhydrazide) (PAHy), a water-soluble synthetic macromolecule, becomes polycationic and potentially useful for systemic gene delivery. Initially the biocompatibility of PAHy and PAHy-GTA derivatives with different degrees of positive charge substitution were studied and it was shown that PAHy-GTA was neither haemolytic nor cytotoxicity up to 1 mg/ml. After intravenous injection (125)I-labelled PAHy-GTA derivative containing 46 mol% (PAHy-GTA(b)) of trimethylammonium groups did not accumulate in the liver (4.1+/-0.9% of the recovered dose after 1 h) but was subjected to renal excretion (45+/-21% of the recovered dose was in the kidneys after 1 h). PAHy-GTA formed complexes with DNA (gel retardation) and they protected against degradation by DNase II. Finally the ability of the PAHy-GTA(b) derivative to mediate the transfection of HepG2 cells using the marker gene beta-galactosidase was studied. The optimum plasmid/polymer mass ratio was examined in comparison to LipofectACE, Lipofectin and polyethylenimine.

Animals↗

Synthesis and biopharmaceutical characterisation of new poly(hydroxyethylaspartamide) copolymers as drug carriers.

Four new poly(hydroxyethylaspartamide)-based copolymers bearing (a) poly(ethylene glycol) 2000, (b) poly(ethylene glycol) 5000, (c) poly(ethylene glycol) 2000 and hexadecylalkyl, (d) poly(ethylene glycol) 5000 and hexadecylalkyle, as pendant groups were synthesised. The copolymers were obtained by partial aminolysis of polysuccinimide with poly(ethylene glycol) and hexadecylalkyl amino derivatives followed by reaction with ethanolamine. Naked polyhydroxyaspartamide was obtained by polysuccinimide reaction with ethanolamine. The nuclear magnetic resonance, infrared, light scattering and elemental analysis allowed for the extensive physico-chemical characterisation of the carriers. The molecular mass of all the polymers was in the range of 27000-34000 Da, and the polydispersivity was in the range of 1.5-1.7. By intravenous injection to mice bearing a solid tumour, all the polymeric carriers displayed a bi-compartmental pharmacokinetic behaviour. Both the poly(ethylene glycol) and the hexadecylalkyle conjugation prolonged and enhanced the distribution phase of poly(hydroxyethylaspartamide). The poly(ethylene glycol) conjugation was found to promote the carrier elimination by kidney ultrafiltration and to prevent partially the accumulation in the spleen and in the liver. The poly(ethylene glycol)/hexadecylalkyle conjugates localised preferentially in the liver were over 30% of the dose/g of tissue was determined after 144 h from administration. In the tumour all the polymers displayed a relevant accumulation that significantly increased throughout the time to reach high concentrations after 24 h. In particular, the poly(ethylene glycol)/hexadecylalkyle conjugates achieved a concentration of 15-25% of the dose/g of tissue after 24 h from administration that was maintained up to 144 h.

Animals↗

Opposing cardioprotective actions and parallel hypertrophic effects of delta PKC and epsilon PKC.

Conflicting roles for protein kinase C (PKC) isozymes in cardiac disease have been reported. Here, deltaPKC-selective activator and inhibitor peptides were designed rationally, based on molecular modeling and structural homology analyses. Together with previously identified activator and inhibitor peptides of epsilonPKC, deltaPKC peptides were used to identify cardiac functions of these isozymes. In isolated cardiomyocytes, perfused hearts, and transgenic mice, deltaPKC and epsilonPKC had opposing actions on protection from ischemia-induced damage. Specifically, activation of epsilonPKC caused cardioprotection whereas activation of deltaPKC increased damage induced by ischemia in vitro and in vivo. In contrast, deltaPKC and epsilonPKC caused identical nonpathological cardiac hypertrophy; activation of either isozyme caused nonpathological hypertrophy of the heart. These results demonstrate that two related PKC isozymes have both parallel and opposing effects in the heart, indicating the danger in the use of therapeutics with nonselective isozyme inhibitors and activators. Moreover, reduction in cardiac damage caused by ischemia by perfusion of selective regulator peptides of PKC through the coronary arteries constitutes a major step toward developing a therapeutic agent for acute cardiac ischemia.

Amino Acid Sequence↗

Ocular tolerability and in vivo bioavailability of poly(ethylene glycol) (PEG)-coated polyethyl-2-cyanoacrylate nanosphere-encapsulated acyclovir.

Acyclovir-loaded polyethyl-2-cyanoacrylate (PECA) nanospheres were prepared by an emulsion polymerization process in the micellar phase and characterized. The influence of the presence of nonionic surfactant as well as other substances [i.e., 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and poly(ethylene glycol) (PEG)], on formulation parameters and loading capacity was investigated. In particular, the presence of PEG resulted in an increase of mean size and size distribution. To obtain PEG-coated PECA nanospheres with a mean size of < 200 nm, Pluronic F68 at concentrations > 1.5% (w/v) should be used during preparation. The presence of PEG also resulted in a change in zeta potential, from -25.9 mV for uncoated nanospheres to -12.2 mV for PEG-coated PECA nanospheres. The presence of HP-beta-CyD elicited an increase of nanosphere size and size distribution, but zeta potential was not influenced. In vitro drug release from nanospheres was determined in both phosphate buffer (pH 7.4) and plasma. The presence of HP-beta-CyD and PEG did not influence the acyclovir release rate in plasma. In the case of release in phosphate buffer, PEG-coated nanospheres showed a slower release. Ocular tolerability of PEG-coated PECA nanospheres was evaluated by the in vivo Draize test. This colloidal carrier was well tolerated, eliciting no particular inflammation at the level of the various ocular structures. In vivo ocular bioavailability was evaluated by instilling 50 microL of the acyclovir-loaded nanospheres only once in the conjunctival sac of rabbit eyes. At various time intervals, aqueous humour acyclovir content was determined by high-performance liquid chromatography. Acyclovir-loaded PEG-coated PECA nanospheres were compared with an aqueous solution of the drug and a physical mixture of acyclovir nanospheres. The acyclovir-loaded PEG-coated PECA nanospheres showed a significant (p < 0.001) increase of drug levels (25-fold) in aqueous humor compared with the free drug or the physical mixture. This finding is probably due to an improved ocular mucoadhesion of PEG-coated PECA nanospheres.

Acyclovir↗

[Arterial aneurysms associated with cystic hepato-renal disease].

BACKGROUND: Ehlers Danlos syndrome (type IV) and kidney and liver cyst disease can present a common factor: anomalous biosynthesis of structural collagen and elastic tissue. We present an exceptional case. CASE REPORT: A 62-year-old man complained of pain in the upper left quadrant of the abdomen. Ultrasonography, magnetic resonance imaging and arteriography evidenced an aneurysm of the splenic artery, an aneurysm of the hypogastric artery, multiple cysts in the kidney and liver, and mitral valvulopathy. Treatment was splenectomy with resection of the splenic aneurysm and resection of the iliac aneurysm and iliac-iliac bypass. DISCUSSION: The association of kidney and liver cyst disease with venous gastrointestinal and cardiovascular complications is well known. The simultaneous presence of cysts and peripheral and visceral aneurysms with anomalies of the arterial wall resembling Ehlers Danlos syndrome (type IV) would suggest that these two diseases might result from a common connective tissue anomaly. The underlying mechanism(s) remain unknown.

Aneurysm↗

Vascular complications of native arteriovenous fistulas for hemodialysis: role of microsurgery.

This article describes the treatment of 56 early and late vascular complications of native arteriovenous fistula (AVF) in patients with end-stage renal disease, between January 1987 and January 1999. Twenty-six were arteriovenous aneurysms and 2 pseudoaneurysms; 25 were thromboses. We also observed two cases of periarteritis associated with systemic lupus erythematosus (SLE) and one complex iatrogenic lesion caused by an attempt at percutaneous restoration of potency. We applied microsurgical principles, instruments, and techniques. It was possible to restore a vascular access at the original site, using the same vessels in 45 cases (80.4%). In 10.7% of cases, we were able to rescue the original AVF by microsurgical revision. A new vascular access had to be created proximally in the same limb or in the contralateral forearm in 11 cases of aneurysms (19.6% of the total, 42% of the aneurysms). After a minimum follow-up of 8 months, a total of four patients had to be reoperated for further complications (7.2%). Our data support the idea that microsurgical treatment of vascular complications of native AVF is highly successful compared with results obtained by conventional surgery and, in a defined subgroup of patients, permits salvage of the fistula.

Aged↗

Cystic peritoneal mesothelioma: report of a case.

Peritoneal mesothelioma is a rare disease, especially when it arises in a cystic form with tardive and often nonspecific symptoms. While diffuse neoplasms have an unfavorable prognosis, cystic forms are usually benign. An accurate diagnosis can only be made only with electron microscopy and immunohistochemical studies. A 92-year-old woman with an ultrastructurally ascertained cystic peritoneal mesothelioma was admitted to the hospital's emergency ward, and was considered to be unusual because of the size of the mass and the patient's age. A review of the literature is made, and the clinical and diagnostic aspects of this disease are also discussed.

Aged↗

Baroreflex failure syndrome after bilateral excision of carotid body tumors: an underestimated problem.

Carotid body tumors (CBTs) are relatively rare paragangliomas that develop from neural crest cells at the bifurcation of the common carotid artery. They are generally slow growing and benign. Excision is currently considered the treatment of choice, although vascular and especially neural injuries are still relatively frequent in patients with large or bilaterally resected tumors. The baroreflex failure syndrome (BFS) has recently been identified as a severe, rarely recognized, and certainly underestimated complication after the bilateral excision of CBTs. The present report describes a case of a bilateral CBT followed by BFS and reviews the experiences reported in the literature. In light of the low incidence of malignancy of these tumors, their biologic behavior, their very high rate of cranial nerve palsy, and the occurrence of BFS in bilaterally resected paragangliomas, the current practice of bilaterally removing these tumors is questioned.

Baroreflex↗