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Biomedical subjects

Vincenzo Giordano

Publications and source records attributed to Vincenzo Giordano.

8 recordsLinked to original sources

Systemic and brain metabolic dysfunction as a new paradigm for approaching Alzheimer's dementia.

Since its definition Alzheimer's disease has been at the centre of consideration for neurologists, psychiatrists, and pathologists. With John P. Blass it has been disclosed a different approach Alzheimer's disease neurodegeneration understanding not only by the means of neurochemistry but also biochemistry opening new scenarios in the direction of a metabolic system degeneration. Nowadays, the understanding of the role of cholesterol, insulin, and adipokines among the others in Alzheimer's disease etiopathogenesis is clarifying approaches valuable not only in preventing the disease but also for its therapy.

Adiponectin↗

Supervisory control of mobile sensor networks: math formulation, simulation, and implementation.

This paper uses a novel discrete-event controller (DEC) for the coordination of cooperating heterogeneous wireless sensor networks (WSNs) containing both unattended ground sensors (UGSs) and mobile sensor robots. The DEC sequences the most suitable tasks for each agent and assigns sensor resources according to the current perception of the environment. A matrix formulation makes this DEC particularly useful for WSN, where missions change and sensor agents may be added or may fail. WSN have peculiarities that complicate their supervisory control. Therefore, this paper introduces several new tools for DEC design and operation, including methods for generating the required supervisory matrices based on mission planning, methods for modifying the matrices in the event of failed nodes, or nodes entering the network, and a novel dynamic priority assignment weighting approach for selecting the most appropriate and useful sensors for a given mission task. The resulting DEC represents a complete dynamical description of the WSN system, which allows a fast programming of deployable WSN, a computer simulation analysis, and an efficient implementation. The DEC is actually implemented on an experimental wireless-sensor-network prototyping system. Both simulation and experimental results are presented to show the effectiveness and versatility of the developed control architecture.

Algorithms↗

Combining genetic algorithms and Lyapunov-based adaptation for online design of fuzzy controllers.

This paper proposes a hybrid approach for the design of adaptive fuzzy controllers (FCs) in which two learning algorithms with different characteristics are merged together to obtain an improved method. The approach combines a genetic algorithm (GA), devised to optimize all the configuration parameters of the FC, including the number of membership functions and rules, and a Lyapunov-based adaptation law performing a local tuning of the output singletons of the controller, and guaranteeing the stability of each new controller investigated by the GA. The effectiveness of the proposed method is confirmed using both numerical simulations on a known case study and experiments on a nonlinear hardware benchmark.

Algorithms↗

Carnitine replacement in end-stage renal disease and hemodialysis.

In patients with chronic renal failure, not yet undergoing hemodialysis (HD), plasma acylcarnitines accumulate in part due to a decreased renal clearance of esterified carnitine moieties. In these patients, a high acylcarnitine/free-carnitine ratio is usually found in plasma. Patients undergoing maintenance HD, usually present with plasma carnitine insufficiency, due to accumulation of metabolic intermediates combined with impaired carnitine biosynthesis, reduced protein intake and increased removal via HD. Plasma carnitine concentrations rapidly decrease to 40% of baseline level during the dialysis session, with a slow restoration of the carnitine concentration during the interdialytic period, mainly from organs of storage (skeletal muscle). Dietary intake also plays an important role in carnitine homeostasis of HD patients since the prevalence of malnutrition ranges from 18% to 75% of these cases. This could differentially affect various body compartments, with clinical consequences such as impaired muscle function, decreased wound healing, altered ventilatory response, and abnormal immune function. Repeated hemodialytic treatments are associated with decreased carnitine stores in skeletal muscle. The administration of intravenous L-carnitine (LC) postdialysis replenishes the free carnitine removed from the blood and contributes to replenishment of muscle carnitine content. LC supplementation in selected uremic patients may yield clinical benefits by ameliorating several conditions, such as erythropoietin-resistant anemia, decreased cardiac performance, intradialytic hypotension, muscle symptoms, as well as impaired exercise and functional capacities. Furthermore, LC may positively influence the nutritional status of HD patients by promoting a positive protein balance, and by reducing insulin resistance and chronic inflammation, possibly through an effect on leptin resistance.

Anemia↗

Effect of tenoxicam on fracture healing in rat tibiae.

BACKGROUND: Nonsteroidal anti-inflammatory drugs have been implicated in the development of delayed unions and nonunion after fractures in animal models. Previous investigations have identified two important factors as determinants of delayed fracture healing: early drug administration and a dose-dependent effect. OBJECTIVE: The purpose of this investigation was to study the effect of tenoxicam, a nonsteroidal anti-inflammatory drug, on the fracture healing process in rat tibiae. METHODS: Fifty-eight Wistar rats were randomly divided in four groups (I, II, III, and IV). Group I (control group, n=12) was given 0.1ml saline solution per day intramuscularly. Groups II (n=12), III (n=12), and IV (n=12) were administered 10mg per kg per day of tenoxicam intramuscularly. Administration of substances was begun on a week before to 48h after the fracturing procedure and continued during the entire experiment. Callus formation was studied histologically and histomorphologically, using light microscopy. In addition, a histologic grading based on the morphologic stage of fracture healing was carried out at 4 weeks, according to the criteria proposed by Allen et al. RESULTS: There was a significant difference in treatment effect between Group I (saline solution) and Groups II, III, and IV (tenoxicam) (P=0.07). Histologically and histomorphologically, there were qualitative and quantitative delay in callus formation at all tenoxicam groups. This was more pronounced the earlier the nonsteroidal anti-inflammatory drug was started, although no significant difference could be detected between Groups II, III, and IV (P>(alpha=10%)). Four weeks after fracture, Group I (n=3) showed complete osseous union, Groups II (n=3) and III (n=3), complete cartilaginous union, and Group IV (n=3), incomplete osseous union, according to Allen et al. By using this rating scale, the difference between control and drug-treated groups was statistically significant (P<0.1). CONCLUSION: Under studied conditions, this investigation shows that administration of tenoxicam intramuscularly delays fracture healing process in rat tibiae. These results suggest the hypothesis that early drug administration may delay bone healing after experimental fractures in animals, although it could not be detected statistically significant.

Animals↗

Antiangiogenic effects of the novel camptothecin ST1481 (gimatecan) in human tumor xenografts.

ST1481 (gimatecan) is a novel lipophilic camptothecin with a promising preclinical pharmacological profile. On the basis of its high antitumor efficacy when delivered by the oral route, the compound is suitable for prolonged administration. This schedule of treatment has been reported as the most appropriate to exploit the antiangiogenic effects of cytotoxic drugs. The aim of the study was to investigate the antiangiogenic and antitumor effects of oral ST1481 in human tumor xenografts. In spite of a marginal drug effect against the s.c. growing A549 lung carcinoma following administration with an intermittent schedule (q4dx4 times, maximum tolerated dose: 2 mg/kg), tumor growth was strongly inhibited by a daily low-dose (0.5 mg/kg) prolonged administration. Immunohistochemical analysis showed a reduced number of microvessels in tumors of both treated groups versus controls and a significantly higher reduction in the daily versus the q4dx4-treated tumors (P < 0.0001, by Student's t test). In our experimental model, the relation between microvessel density and tumor size (r = 0.738, by the Spearman rank test) suggests a role of inhibition of tumor vasculature in tumor response. Significant inhibition of tumor angiogenesis (P < 0.0001 versus control tumors) was observed even with a very low drug dose (0.06 mg/kg) in the orthotopically implanted (i.d.) MeWo melanoma, under conditions causing minimal tumor growth inhibition. Additional evidences of the antiangiogenic activity of ST1481 were provided by antimotility effects on endothelial cells, in vivo inhibition of vascularization in the Matrigel assay, and down-regulation of the expression of the proangiogenic basic fibroblast growth factor in A549 tumor cells associated with inhibition of the pathway involving Akt. In conclusion, the available results support the possibility that the antiangiogenic properties of ST1481 contribute to its antitumor potential and that this effect might be enhanced by the continuous low-dose treatment.

Administration, Oral↗

Compression of the medial branch of the deep peroneal nerve, relieved by excision of an os intermetatarseum. A case report.

The authors report a case of direct compression of the medial branch of the deep peroneal nerve by an os intermetatarseum in a 52-year-old female patient who was referred to their Institution because of pain over the dorsum of her left foot associated with paraesthesias in the first web space. Examination disclosed a positive Tinel sign over the dorsal aspect of the first metatarsal bone. Plain radiographs revealed a small, irregular accessory ossicle on the dorsum of the left foot, between the medial cuneiform and first and second metatarsals. At operation, the os intermetatarseum was found to impinge on the medical branch of the deep peroneal nerve. Excision of the os intermetatarseum and nerve decompression was performed. After four years, the patient has normal function and is completely relieved of her symptoms.

Female↗

Bis-indols: a novel class of molecules enhancing the cytodifferentiating properties of retinoids in myeloid leukemia cells.

Enhancing the pharmacologic activity of all-trans retinoic acid (ATRA) is potentially useful in the management of acute promyelocytic leukemia (APL) and other types of myeloid leukemia. In this report, we identify a novel class of experimental agents selectively potentiating the cytodifferentiating activity of ATRA and synthetic retinoic acid receptor alpha agonists in APL and other myeloid leukemia cell lines. These agents have a bis-indolic structure (BISINDS), and ST1346 is the prototypical compound of the series. Gene-profiling experiments and determination of the level of expression of myeloid-associated markers indicate that ST1346 stimulates many aspects of the granulocytic maturation process set in motion by ATRA. Stimulation of the cytodifferentiating activity of ATRA by ST1346 enhances the efficacy of the retinoid in vivo, as demonstrated in the APL model of the severe combined immunodeficiency (SCID) mouse receiving transplants of NB4 cells. Although the molecular mechanisms underlying the ATRA-potentiating action of ST1346 and congeners have not been completely clarified, bis-indols are not ligands and do not exert any direct effect on the ATRA-dependent transactivation of nuclear receptors. However, ST1346 inhibits the down-regulation of cyclic adenosine monophosphate (cAMP)-dependent CREB transcriptional complexes and enhances the level of expression of signal transducers and activators of transcription-1 (STAT1), 2 putative molecular determinants of the differentiation process activated by ATRA in APL cells. More importantly, ST1346 relieves the down-regulation of Jun N-terminal kinases (JNK) afforded by ATRA. In addition, a specific JNK inhibitor blocks the enhancing effect of ST1346 on ATRA-induced maturation of NB4 cells. This demonstrates an important role for the mitogen-activated protein kinase in the molecular mechanisms underlying the pharmacologic activity of the bis-indol.

Antineoplastic Agents↗