PubMed Health⌕ Search

Biomedical subjects

Marco Esposito

Publications and source records attributed to Marco Esposito.

16 recordsLinked to original sources

Nitazoxanide, a broad-spectrum thiazolide anti-infective agent for the treatment of gastrointestinal infections.

Colonisation of the gastrointestinal tract by anaerobic bacteria, protozoa, trematodes, cestodes and/or nematodes and other infectious pathogens, including viruses, represents a major cause of morbidity and mortality in Africa, South America and southeast Asia, as well as other parts of the world. Nitazoxanide is a member of the thiazolide class of drugs with a documented broad spectrum of activity against parasites and anaerobic bacteria. Moreover, the drug has recently been reported to have a profound activity against hepatitis C virus infection. In addition, nitazoxanide exhibits anti-inflammatory properties, which have prompted clinical investigations for its use in Crohn's disease. Studies with nitazoxanide derivatives have determined that there must be significantly different mechanisms of action acting on intracellular versus extracellular pathogens. An impressive number of clinical studies have shown that the drug has an excellent bioavailability in the gastrointestinal tract, is fast acting and highly effective against gastrointestinal bacteria, protozoa and helminthes. A recent Phase II study has demonstrated viral response (hepatitis C) to monotherapy, with a low toxicity and an excellent safety profile over 24 weeks of treatment. Pre-clinical studies have indicated that there is a potential for application of this drug against other diseases, not primarily affecting the liver or the gastrointestinal tract.

Animals↗

In vivo cytokine secretion and NF-kappaB activation around titanium and copper implants.

The early biological response at titanium (Ti), copper (Cu)-coated Ti and sham sites was evaluated in an in vivo rat model. Material surface chemical and topographical properties were characterized using Auger electron spectroscopy, energy dispersive X-ray spectroscopy and interferometry, respectively. The number of leukocytes, cell types and cell viability (release of lactate dehydrogenase) were determined in the implant-interface exudate. The contents of activated nuclear transcription factor NF-kappaB, interleukin-6 (IL-6) and interleukin-10 (IL-10) were determined by enzyme linked immunosorbent assay. An increase in the number of leukocytes, in particular, polymorphonuclear leukocytes, was observed between 12 and 48 h around Cu. A marked decrease of exudate cell viability was found around Cu after 48 h. The total amounts of activated NF-kappaB after 12 h was highest in Ti exudates whereas after 48 h the highest amount of NF-kappaB was detected around Cu. The levels of cytokine IL-6 were consistently high around Cu at both time periods. No differences in IL-10 contents were detected, irrespective of material/sham and time. The results show that materials with different toxicity grades (titanium with low and copper with high toxicity) exhibit early differences in the activation of NF-kappaB, extracellular expression and secretion of mediators, causing major differences in inflammatory cell accumulation and death in vivo.

Animals↗

Monocyte viability on titanium and copper coated titanium.

The role of apoptosis/cell death in the inflammatory response at the implanted materials is unexplored. Two surfaces with different cytotoxic potential and in vivo outcomes, titanium (Ti) and copper (Cu) were incubated in vitro with human monocytes and studied using a method to discriminate apoptotic and necrotic cells (Annexin V/PI staining). Further, staurosporine, a potent inducer of apoptosis, was added to the surface adherent monocytes. Lactate dehydrogenase (a marker of cell membrane injury) and TNF-alpha and IL-10, cytokines, previously suggested to play a major role in the monocyte apoptosis, were assayed in the culture medium. The results demonstrated that Ti surfaces displayed enhanced monocyte survival and production of IL-10 and TNF-alpha. Cu adherent cells exhibited apoptotic signs as early as 1h after incubation. In contrast to Ti, after 48 h the predominance of apoptotic cells switched to apoptotic/necrotic cells on Cu surfaces. Staurosporine treatment of Ti adherent cells mediated similar type of cell death. LDH and cytokine contents were low around Cu surfaces, partly explained by interference between Cu ions and LDH and cytokines. This study suggests that material properties rapidly influence the onset of human monocyte apoptosis and progression to late apoptosis/necrosis. Early detection of apoptosis and cell death may be important for the understanding of the biological response to implanted materials.

Annexin A5↗

In vitro efficacies of nitazoxanide and other thiazolides against Neospora caninum tachyzoites reveal antiparasitic activity independent of the nitro group.

The thiazolide nitazoxanide [2-acetolyloxy-N-(5-nitro-2-thiazolyl)benzamide] (NTZ) exhibits a broad spectrum of activities against a wide variety of intestinal and tissue-dwelling helminths, protozoa, and enteric bacteria infecting animals and humans. The drug has been postulated to act via reduction of its nitro group by nitroreductases, including pyruvate ferredoxin oxidoreductase. In this study, we investigated the efficacies of nitazoxanide and a number of other thiazolides against Neospora caninum tachyzoites in vitro. We employed real-time-PCR-based monitoring of tachyzoite adhesion, invasion, and intracellular proliferation, as well as electron microscopic visualization of the effects imposed by nitazoxanide. In addition, we investigated several modified versions of this drug. These modifications included on one hand the replacement of the nitro group on the thiazole ring with a bromide, thus removing the most reactive group, and on the other hand the differential positioning of methyl groups on the salicylate ring. We show that the thiazole-associated nitro group is not necessarily required for the action of the drug and that methylation of the salicylate ring can result in complete abrogation of the antiparasitic activity, depending on the positioning of the methyl group. These findings indicate that other mechanisms besides the proposed mode of action involving the pyruvate ferredoxin oxidoreductase enzyme could be responsible for the wide spectrum of antiparasitic activity of NTZ and that modifications in the benzene ring could be important in these alternative mechanisms.

Animals↗

The role of implant surface modifications, shape and material on the success of osseointegrated dental implants. A Cochrane systematic review.

We tested the hypothesis of no difference in implant failures between various dental implant types. We searched for all randomised clinical trials comparing different implant types/systems with a follow up of at least one year on four databases. Screening of eligible trials, quality assessment and data extraction were conducted in duplicate. Thirty-one trials were identified. Twelve trials, reporting results of 512 patients, were included. No significant differences were observed for implant failures. There were minor statistically significant differences for peri-implant bone level changes. Turned surfaces had a 20% reduction in risk of being affected by perimplantitis over a 3-year period.

Dental Implantation, Endosseous↗

The role of B- and T-cell immunity in toltrazuril-treated C57BL/6 WT, microMT and nude mice experimentally infected with Neospora caninum.

Neospora caninum is a protozoan parasite predominantly known for causing abortion in cattle and neuromuscular disease in dogs. So far, no efficient metaphylactic chemotherapy has been developed. In preliminary studies, toltrazuril had been successfully used against experimental neosporosis in mice and calves. In the present study, we used immunocompetent and immunodeficient mouse strains to address the role of immunity in supporting the chemotherapy of experimental N. caninum infection. WT, microMT and athymic nude mice were intraperitoneally inoculated with 1x10(6) Nc-1 tachyzoites. The drug was administered in the drinking water for 6 consecutive days so as to obtain a daily dose of approximately 20 mg toltrazuril/kg body weight. The course of infection was monitored by clinical, histological and immunohistochemical means, as well as by the search for parasite DNA using PCR-analyses of various organs. In immunocompetent WT mice, treatment proved to be of high efficacy by abrogation of any lesion formation or PCR-positivity in medicated C57BL/6 mice and a significant reduction of lesion formation or PCR-positivity in BALB/c animals. Similarly, treated microMT mice exhibited a significant reduction in cerebral lesion formation as well as in parasite DNA detectability by PCR when compared to untreated animals. Athymic nude mice, however, did not respond to treatment in that only a delay of the parasite dissemination was achieved, and nude mice still showed the neosporosis disease symptoms, although later than untreated animals. We conclude that treatment with toltrazuril appears to act parasitostatically rather than parasitocidically. This is supported by the fact that: (1) although the lack of B-cells did not impair the effect of toltrazuril, (2) the lack of T-cells did not allow for a full efficacy of treatment. Therefore, chemotherapy with toltrazuril against experimental infections with N. caninum requires the support of T-cell immunity in order to be successful.

Administration, Oral↗

Enamel matrix derivative for periodontal tissue regeneration in treatment of intrabony defects: a Cochrane systematic review.

We reviewed the literature on the efficacy of enamel matrix derivative (EMD) in comparison with open flap debridement, guided tissue regeneration (GTR), and bone grafting for the treatment of intrabony defects. We searched four major electronic databases for randomized controlled trials (RCTs) with at least one year of follow-up. Several journals were handsearched with no language restrictions. Outcome measures were: tooth loss, changes in probing attachment levels (PAL), pocket depths (PPD), gingival recessions (REC), marginal bone levels on intraoral radiographs, and postoperative infections. Screening of eligible RCTs, assessment of the methodological quality, and data extraction were conducted in duplicate. No difference in tooth loss was observed. A meta-analysis (eight trials) showed that EMD-treated sites displayed statistically significant PAL improvements (mean difference 1.3 mm) and PPD reduction (1 mm) when compared to flap surgery. When EMD was compared to GTR (six trials), GTR showed a statistically significant reduction of PPD (0.6 mm) and increase of REC (0.5 mm). No difference in postoperative infections was observed. No trials compared EMD with bone grafts alone. EMD is able to significantly improve PAL levels and PPD reduction when compared to flap surgery; however, there is no evidence that more teeth could be saved. There was no evidence of important differences between EMD and GTR.

Alveolar Bone Loss↗

Short-term bone response to titanium implants coated with thin radiofrequent magnetron-sputtered hydroxyapatite in rabbits.

BACKGROUND: It has been suggested that calcium phosphate (CaP) coatings initiate faster bone growth around implants. A major concern about the viable use of these coatings has been their biologic performance related to the coating characteristics. PURPOSE: The purpose of this study was to investigate the early bone response to micron- and submicron-thick hydroxyapatite (HA) coatings in cortical and trabecular bone. MATERIALS AND METHODS: CaP coatings were manufactured by magnetron sputtering. Heat treatment was subsequently used to increase the crystallinity of the coatings. Coatings were characterized by x-ray diffraction, Fourier transform infrared spectroscopy, inductively coupled plasma optical emission spectroscopy (ICP-OES), and stylus profilometry. Four types of CaP-coated implants were used (0.1 microm and 2.0 microm amorphous; 0.1 microm and 2.0 microm crystalline); uncoated machined commercially pure titanium implants served as controls. Four hundred eighty implants were randomly placed in 60 rabbits. Ten animals were followed up for 1 week, 10 for 3 weeks, and 40 for 6 weeks. The bone response was histomorphometrically evaluated. RESULTS: Coatings with a CaP ratio very close to that of HA were produced. Crystalline coatings significantly improved the early bone-implant contact whereas the amorphous-coated implants behaved similarly to uncoated titanium. CONCLUSIONS: Crystalline CaP coatings 100 nm thick on titanium implants elicited an improved early bone response compared with that of uncoated titanium implants. No further improvement in the bone response was observed with 2 microm coatings.

Animals↗

Therapeutic use of hyperbaric oxygen for irradiated dental implant patients: a systematic review.

The aim of this systematic review was to investigate the effectiveness of hyperbaric oxygen (HBO) therapy for irradiated patients who require dental implants using data from randomized controlled clinical trials (RCTs). The review was prepared according to Cochrane Collaboration guidelines. The Cochrane Oral Health Group Specialist Register and the Cochrane Controlled Trials Register were searched (Cochrane Library 2002, Issue 2), together with Medline from 1966 or Embase from 1974. Several journals were hand-searched, and fifty-five implant manufacturers were contacted in an attempt to identify ongoing or unpublished studies. The results were that no RCTs comparing HBO with no HBO for implant treatment in irradiated patients were identified. Our principal conclusions are that clinicians ought to be aware and make patients aware of the lack of reliable clinical evidence for or against the clinical effectiveness of HBO therapy in irradiated patients requiring dental implants. There is a need for RCTs to determine the effectiveness of HBO.

Cranial Irradiation↗

Morphologic and immunohistochemical observations of tissues surrounding retrieved transvenous pacemaker leads.

Immunohistochemical and morphologic techniques were employed to evaluate the tissue response around chronically implanted pacing leads. Seventeen leads were retrieved from 12 patients. Leads were extracted by direct manual traction (1), extraction with sheaths and locking stylets (1), or with by a combination of mechanical tools and Excimer laser sheaths (15). Mean lead implantation time was 5.6 years (range 1-8 years). Frozen sections, 6-8 microm thick, were incubated with antibodies against HLA-DR antigen, endothelial cells, macrophages, T cells, plasma cells, fibrinogen, and interleukin-1beta. Prominent morphologic observations were fibrous encapsulations of the leads. Immunohistochemical analysis revealed a tissue generally devoid of inflammatory and immune cells. The fibrous capsule surrounding the lead was partially or completely covered with a monolayer of CD34 expressing endothelial cells. The results from this study provide useful information in design and material selection for pacemaker leads. Endothelialization of the fibrous encapsulation indicates a functionalization of blood-contacting surfaces around pacemaker materials, thus providing a mechanism for long-term persistence of foreign materials in the blood. The laser method allowed an efficient extraction of pacemaker leads without damage to the studied tissues, as suggested by the presence of immunolabeled cells close to the cut surfaces.

Adult↗

The reporting of randomized controlled trials in prosthodontics.

PURPOSE: This article evaluates the reporting of randomized controlled trials (RCT) in prosthodontics, excluding endosseous implant-based prosthetics. MATERIALS AND METHODS: Reports of RCTs published to the end of 2000 in any language were identified using a multilayered search strategy. The Cochrane Oral Health Group specialized register, Medline, and personal libraries were searched. Three researchers appraised the articles independently using guidelines following Jadad and CONSORT, complemented with an evaluation of the appropriateness of the reported statistics. RESULTS: Ninety-two reports of RCTs were evaluated, covering a wide spectrum of study hypotheses, topics, and issues within various prosthodontic domains. The interrater agreements on appraisal criteria were relatively high, with median kappa values ranging between 0.65 and 0.79. The reports were in general of poor methodologic quality. Randomization and procedures for concealment allocation were not described in 70% of the articles. The methods used to generate the random allocation sequence were not mentioned in 82%. The methods used to implement the random allocation sequence, clarifying whether it was concealed until all interventions were assigned, was not mentioned in 94%. Reporting who generated allocation sequence, who enrolled patients, and who assigned participants to groups was not reported in 7%. Reasons for withdrawals were not given in 23% of the reports. No attempt at blinding was reported in 72%. Statistical analysis was not described in 6% of the papers, while these analyses were assessed as appropriate for 75%, unclear in 12%, and inappropriate in 7%. CONCLUSION: Few RCTs in prosthodontics are reported in accordance with contemporary guidelines for adequate reporting of trials.

Adhesives↗

Long-term bone response to titanium implants coated with thin radiofrequent magnetron-sputtered hydroxyapatite in rabbits.

PURPOSE: The present study was designed to investigate the long-term bone response around machined screw-type uncoated and calcium phosphate (CaP) -coated commercially pure titanium implants. MATERIALS AND METHODS: Using a magnetron sputtering technique, implants with a CaP coating similar in composition and CaP ratio to hydroxyapatite were produced. Heat treatment was subsequently used to increase the crystallinity of the coatings. Four types of coatings (0.1 and 2.0 microm amorphous and 0.1 and 2.0 microm crystalline) were manufactured; uncoated implants served as a control. Three hundred twenty implants (64 of each type) were randomly placed in the tibial cortical and trabecular femoral bones of 40 rabbits. The rabbits were sacrificed 9 months after implant placement. RESULTS: Histomorphometric evaluation carried out on ground sections revealed that the crystalline CaP coatings achieved the highest bone-implant contact in both tibiae and femora compared with amorphous CaP-coated and uncoated titanium. DISCUSSION: The present study suggests that submicron crystalline hydroxyapatite coating adds bioactive properties to titanium oral implants. CONCLUSION: An ultra-thin, 0.1-microm crystalline CaP coating can elicit and maintain an improved long-term bone response compared to amorphous coated or uncoated Ti implants, without any adverse tissue reactions.

Analysis of Variance↗

A 5-year follow-up comparative analysis of the efficacy of various osseointegrated dental implant systems: a systematic review of randomized controlled clinical trials.

PURPOSE: To test the null hypothesis that there is no difference in failure rates between various root-formed osseointegrated dental implant systems after 5 years of loading. MATERIALS AND METHODS: A search was conducted for all randomized controlled clinical trials (RCTs) comparing different implant systems with a follow-up of 5 years. The Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, and EMBASE were searched. Several dental journals were also searched by hand. Written contacts were established with authors of the identified RCTs and with more than 55 oral implant manufacturers and personal contacts to identify unpublished RCTs. No language restriction was applied. The last electronic search was conducted on February 1, 2005. Screening of eligible studies, quality assessment, and data extraction were conducted in duplicate. Results were expressed as random effect models using weighted mean differences for continuous outcomes and relative risk for dichotomous outcomes with 95% confidence intervals. RESULTS: Ten RCTs were identified. Four of these RCTs, reporting results from a total of 204 patients, were considered suitable for inclusion. Six different implant types were compared. On a per-patient rather than a per-implant basis, there were no statistically significant differences, with the exception of more marginal bone loss around early loaded Southern implants when compared to early loaded Steri-Oss implants (mean difference -0.35 mm; 95% CI -0.70 to -0.01). However, the difference disappeared in the meta-analysis. DISCUSSION AND CONCLUSIONS: There were no clinical differences among implant systems. However, these findings are based on only 4 RCTs with few participants. More RCTs should be conducted with larger patient samples.

Dental Implantation, Endosseous↗