Advances in Hollow Inorganic Nanomedicines for Photothermal-Based Therapies.

Nanotechnology has prompted the development of hollow inorganic nanomedicine. These medicines are now widely investigated as photothermal-based therapies for various diseases due to their high loading capacity, tuneable wavelength, relatively small size and low density. We begin this review with a brief introduction, followed by a summary of the development of imaging-guided photothermal therapy (PTT) for cancer treatment during the last three years (from 2017 to 2020). We then introduce the antibacterial effects of these medicines on some bacterial infections, in which the pathogenic bacteria can be killed by mild photothermal effects, ions and antibiotic release. Other diseases can also be treated using hollow inorganic photothermal agents. Specifically, we discuss the use of PTT for treating Alzheimer's disease, obesity and endometriosis. Finally, we share our perspectives on the current challenges and future prospects of using hollow inorganic materials in clinical PTT for various diseases.

Advancements in Adjuvanticity of Bioactive Inorganic and Organic Compounds.

BACKGROUND: Regardless of the enormous success of vaccines over decades, the formulation of biocompatible and highly effective vaccines is still insufficient for combating new pathogens. DISCUSSION: The degree of effectiveness of any vaccine largely depends on the choice of appropriate adjuvant. Along with the optimum biocompatibility, an ideal adjuvant must be biodegradable, economical and easy to manufacture. To date, various organic and inorganic substances have been used as an adjuvant to augment the effectiveness of the vaccine. Immunological adjuvants are essential for strong and long-term effects against various pathogens. However, a very limited number of licensed adjuvants are available for the formulation of a successful vaccine. This leads to a challenging situation in medical science. CONCLUSION: The present review concisely summarizes the mechanism of action of various bioactive organic and inorganic immunological adjuvants, their limitations and future perspectives for their appropriate modification. Current trends of anticancer therapies using immunological adjuvants have also been highlighted in this review.

Eficacia clínica del MTA en Pulpotomías de pacientes pediátricos: Una Revisión Sistemática / Eficácia Clínica da MTA em Pulpotomias Pediátricas de Pacientes: Uma Revisão Sistemática / Clinical Efficacy of MTA in Pediatric Patient Pulpotomies: A Systematic Review

Objetivo: Analizar la eficacia clínica del Agregado Trióxido Mineral (MTA) en pulpotomías a través de estudios comparativos con el formocresol, sulfato férrico e hidróxido de calcio; en pacientes pediátricos con edad de tres a nueve años. Materiales y Métodos: El artículo se basa en una revisión sistemática de la literatura, por ello, se utilizaron como fuentes de información las bases de datos: PubMed, Scielo, y Biblioteca Virtual de Salud. Asimismo, como criterios de inclusión se establecieron publicaciones del año 2008 al 2019, cuya procedencia se derivó de journalsy revistas académicas arbitradas; los cuales permitieron obtener dieciséis ensayos que evaluaban la eficacia clínica a través de los signos y síntomas de las patologías pulpares más comunes: absceso, inflamación gingival, movilidad patológica, dolor a la percusión y dolor espontáneo. Resultados: El MTA obtuvo una eficacia de 97,9% en contraposición al 86,9% del Sulfato Férrico. En relación al Formocresol, el MTA logró el 99% contra un 98,3% de eficacia. Además, en la comparación del MTA con el Hidróxido de Calcio el primero logró un 98,2% y el segundo 74,5%. Conclusiones: El MTA obtuvo una mayor eficacia clínica debido a su biocompatibilidad, pH básico y su elevada facultad al sellar la cámara pulpar. Por lo tanto, puede emplearse como un material seguro para las pulpotomías de pacientes pediátricos.

Objetivo: Analisar a eficácia clínica do Agregado de Trióxido Mineral (MTA) em pulpotomias através de estudos comparativos com formocresol, sulfato férrico e hidróxido de cálcio; em pacientes pediátricos de três a nove anos de idade. Materiais e Métodos: O artigo é baseado em uma revisão sistemática da literatura, portanto, bases de dados foram utilizadas como fontes de informação: PubMed, Scielo, e Biblioteca Virtual. Da mesma forma, como critério de inclusão, foram estabelecidas publicações de 2008 a 2019, cuja origem foi derivada de periódicos e revistas acadêmicas de referência; o que nos permitiu obter dezesseis ensaios que avaliaram a eficácia clínica através dos sinais e sintomas das doenças mais comuns da polpa: abscesso, inflamação gengival, mobilidade patológica, dor na percussão e dor espontânea. Resultados: A MTA obteve uma eficácia de 97,9% contra 86,9% para o sulfato férrico. Em relação ao Formocresol, o MTA alcançou 99% contra 98,3% de eficácia. Além disso, na comparação do MTA com o hidróxido de cálcio, o primeiro atingiu 98,2% e o segundo 74,5%. Conclusões: A MTA obteve uma maior eficácia clínica devido a sua biocompatibilidade, pH básico e sua alta faculdade ao selar a câmara de celulose. Portanto, pode ser usado como material segura para pulpotomias de pacientes pediátricos.

Objective: To analyze the clinical efficacy of the Mineral Trioxide Aggregate (MTA) in pulpotomies through comparative studies with formocresol, ferric sulfate and calcium hydroxide; in pediatric patients aged three to nine years. Materials and Methods: The article is based on a systematic review of the literature, therefore, databases were used as sources of information: PubMed, Scielo, and Virtual Health Library. Likewise, as inclusion criteria, publications from 2008 to 2019 were established, whose origin was derived from journals and refereed academic journals; which allowed us to obtain sixteen trials that evaluated clinical efficacy through the signs and symptoms of the most common pulp diseases: abscess, gingival inflammation, pathological mobility, pain on percussion and spontaneous pain. Results: MTA obtained an efficacy of 97.9% as opposed to 86.9% for ferric sulfate. Concerning to Formocresol, MTA achieved 99% versus 98.3% efficacy. Also, in the comparison of MTA with Calcium Hydroxide, the former achieved 98.2% and the latter 74.5%. Conclusions: MTA obtained a higher clinical efficacy due to its biocompatibility, basic pH and its high faculty when sealing the pulp chamber. Therefore, it can be used as a safe material for pediatric patient pulpotomies.

Biodegradable Inorganic Nanoparticles for Cancer Theranostics: Insights into the Degradation Behavior.

Inorganic nanoparticles as a versatile nanoplatform have been broadly applied in the diagnosis and treatment of cancers due to their inherent superior physicochemical properties (including magnetic, thermal, optical, and catalytic performance) and excellent functions (e.g., imaging, targeted delivery, and controlled release of drugs) through surface functional modification or ingredient dopant. However, in practical biological applications, inorganic nanomaterials are relatively difficult to degrade and excrete, which induces a long residence time in living organisms and thus may cause adverse effects, such as inflammation and tissue cysts. Therefore, the development of biodegradable inorganic nanomaterials is of great significance for their biomedical application. This Review will focus on the recent advances of degradable inorganic nanoparticles for cancer theranostics with highlight on the degradation mechanism, aiming to offer an in-depth understanding of degradation behavior and related biomedical applications. Finally, key challenges and guidelines will be discussed to explore biodegradable inorganic nanomaterials with minimized toxicity issues, facilitating their potential clinical translation in cancer diagnosis and treatment.

Effect of Inorganic Nitrite vs Placebo on Exercise Capacity Among Patients With Heart Failure With Preserved Ejection Fraction: The INDIE-HFpEF Randomized Clinical Trial.

Importance: There are few effective treatments for heart failure with preserved ejection fraction (HFpEF). Short-term administration of inorganic nitrite or nitrate preparations has been shown to enhance nitric oxide signaling, which may improve aerobic capacity in HFpEF. Objective: To determine the effect of 4 weeks' administration of inhaled, nebulized inorganic nitrite on exercise capacity in HFpEF. Design, Setting, and Participants: Multicenter, double-blind, placebo-controlled, 2-treatment, crossover trial of 105 patients with HFpEF. Participants were enrolled from July 22, 2016, to September 12, 2017, at 17 US sites, with final date of follow-up of January 2, 2018. Interventions: Inorganic nitrite or placebo administered via micronebulizer device. During each 6-week phase of the crossover study, participants received no study drug for 2 weeks (baseline/washout) followed by study drug (nitrite or placebo) at 46 mg 3 times a day for 1 week followed by 80 mg 3 times a day for 3 weeks. Main Outcomes and Measures: The primary end point was peak oxygen consumption (mL/kg/min). Secondary end points included daily activity levels assessed by accelerometry, health status as assessed by the Kansas City Cardiomyopathy Questionnaire (score range, 0-100, with higher scores reflecting better quality of life), functional class, cardiac filling pressures assessed by echocardiography, N-terminal fragment of the prohormone brain natriuretic peptide levels, other exercise indices, adverse events, and tolerability. Outcomes were assessed after treatment for 4 weeks. Results: Among 105 patients who were randomized (median age, 68 years; 56% women), 98 (93%) completed the trial. During the nitrite phase, there was no significant difference in mean peak oxygen consumption as compared with the placebo phase (13.5 vs 13.7 mL/kg/min; difference, -0.20 [95% CI, -0.56 to 0.16]; P = .27). There were no significant between-treatment phase differences in daily activity levels (5497 vs 5503 accelerometry units; difference, -15 [95% CI, -264 to 234]; P = .91), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (62.6 vs 61.9; difference, 1.1 [95% CI, -1.4 to 3.5]; P = .39), functional class (2.5 vs 2.5; difference, 0.1 [95% CI, -0.1 to 0.2]; P = .43), echocardiographic E/e' ratio (16.4 vs 16.6; difference, 0.1 [95% CI, -1.2 to 1.3]; P = .93), or N-terminal fragment of the prohormone brain natriuretic peptide levels (520 vs 533 pg/mL; difference, 11 [95% CI, -53 to 75]; P = .74). Worsening heart failure occurred in 3 participants (2.9%) during the nitrite phase and 8 (7.6%) during the placebo phase. Conclusions and Relevance: Among patients with HFpEF, administration of inhaled inorganic nitrite for 4 weeks, compared with placebo, did not result in significant improvement in exercise capacity. Trial Registration: ClinicalTrials.gov Identifier: NCT02742129.

Inorganic nanoparticles in diagnosis and treatment of breast cancer.

Nanoparticles are being actively developed for biomolecular profiling of cancer biomarkers, tumor imaging in vivo, and targeted drug delivery. These nanotechnology-based techniques can be applied widely in the management of different malignant diseases, such as breast cancer. Although the number of different types of nanoparticles is increasing rapidly, most can be classified into two major types: particles that contain organic molecules as a major building material (such as dendrimers, micelles, liposomes and carbon nanotubes, and other polymers); and those that use inorganic elements, usually metals, as a core. In particular, inorganic nanoparticles have received increased attention in the recent past as potential diagnostic and therapeutic systems in the field of oncology. This review primarily discusses progress in applications of inorganic nanoparticles for breast cancer imaging and treatment.

Acoustic Cavitation Enhances Focused Ultrasound Ablation with Phase-Shift Inorganic Perfluorohexane Nanoemulsions: An In Vitro Study Using a Clinical Device.

Purpose. To investigate whether acoustic cavitation could increase the evaporation of a phase-shift inorganic perfluorohexane (PFH) nanoemulsion and enhance high intensity focused ultrasound (HIFU) ablation. Materials and Methods. PFH was encapsulated by mesoporous silica nanocapsule (MSNC) to form a nanometer-sized droplet (MSNC-PFH). It was added to a tissue-mimicking phantom, whereas phosphate buffered saline (PBS) was added as a control (PBS-control). HIFU (P ac = 150 W, t = 5/10 s) exposures were performed in both phantoms with various duty cycles (DC). US images, temperature, and cavitation emissions were recorded during HIFU exposure. HIFU-induced lesions were measured and calculated. Results. Compared to PBS-control, MSNC-PFH nanoemulsion could significantly increase the volume of HIFU-induced lesion (P < 0.01). Peak temperatures were 78.16 ± 5.64°C at a DC of 100%, 70.17 ± 6.43°C at 10%, 53.17 ± 4.54°C at 5%, and 42.00 ± 5.55°C at 2%, respectively. Inertial cavitation was much stronger in the pulsed-HIFU than that in the continuous-wave HIFU exposure. Compared to 100%-DC exposure, the mean volume of lesion induced by 5 s exposure at 10%-DC was significantly larger, but smaller at 2%-DC. Conclusions. MSNC-PFH nanoemulsion can significantly enhance HIFU ablation. Appropriate pulsed-HIFU exposure could significantly increase the volume of lesion and reduce total US energy required for HIFU ablation.

Nanoparticles in medicine: Current challenges facing inorganic nanoparticle toxicity assessments and standardizations.

Although nanoparticles research is ongoing since more than 30years, the development of methods and standard protocols required for their safety and efficacy testing for human use is still in development. The review covers questions on toxicity, safety, risk and legal issues over the lifecycle of inorganic nanoparticles for medical applications. The following topics were covered: (i) In vitro tests may give only a very first indication of possible toxicity as in the actual methods interactions at systemic level are mainly neglected; (ii) the science-driven and the regulation-driven approaches do not really fit for decisive strategies whether or not a nanoparticle should be further developed and may receive a kind of "safety label". (iii) Cost and time of development are the limiting factors for the drug pipeline. Knowing which property of a nanoparticle makes it toxic it may be feasible to re-engineer the particle for higher safety (safety by design). FROM THE CLINICAL EDITOR: Testing the safety and efficacy of nanoparticles for human use is still in need of standardization. In this concise review, the author described and discussed the current unresolved issues over the application of inorganic nanoparticles for medical applications.

Response of E. faecalis biofilms to different associations of auxiliary substances during root canal preparation: a confocal laser microscopy analysis.

OBJECTIVE: This in vitro study evaluated the effect of different endodontic auxiliary chemical substances over Enterococcus faecalis (Ef) biofilm through confocal laser scanning microscopy (CLSM). METHODS: Forty-five bovine incisors were infected with Ef for 21 days. Teeth were divided into five groups: group 1: 2.5% NaOCl + EDTA, group 2: 2% CHX gel + EDTA, group 3: 2% CHX liquid + EDTA, group 4: 2.5% NaOCl + 2% CHX gel + EDTA, group 5: 2.5% NaOCl + 2% CHX liquid + EDTA and a negative and a positive control group (NCG; PCG). The samples were stained with SYTO9 and propidium iodide and analyzed by CLSM. Bacterial viability was quantitatively analyzed by the proportions of dead and live bacteria in the biofilm remnants. Scores were standardized according to the total bacterial load (TBL)-1: ≤ 25%, 2: >25 ≤ 50%, 3: >50 ≤ 75%, 4: >75% and debris-1: absence of debris; 2: presence of debris. Statistical analysis was carried out through the Kruskal-Wallis and the Fischer exact tests (P = 0.05). RESULTS: No statistical differences were observed to CFU, debris and bacterial viability. CONCLUSION: None of the tested substances could completely eliminate Ef from the root canal space.

Surface engineering of inorganic nanoparticles for imaging and therapy.

Many kinds of inorganic nanoparticles (NPs) including semiconductor, metal, metal oxide, and lanthanide-doped NPs have been developed for imaging and therapy applications. Their unique optical, magnetic, and electronic properties can be tailored by controlling the composition, size, shape, and structure. Interaction of such NPs with cells and/or in vivo compartments is critically determined by the surface properties, and sophisticated control over the NP surface is essential to control their fate in biological environments. We review NP surface coating strategies using the categories of small surface ligand, polymer, and lipid. Use of small ligand molecules has the advantage of maintaining the minimal hydrodynamic (HD) size. Polymers can be advantageous in NP anchoring by combining multiple affinity groups. Encapsulation of NPs in polymers, lipids or surfactants can preserve the as-synthesized NPs. NP surface properties and reaction conditions should be carefully considered to obtain a bioconjugate that maintains the physicochemical properties of NP and functionalities of the conjugated biomolecules. We highlight how the surface properties of NPs impact their interactions with cells and in vivo compartments, especially focused on the important surface design parameters such as HD size, surface charge, and targeting. Typically, maximal cellular uptake can take place in the intermediate NP size range of 40-60nm. Clearance of NPs from blood circulation is largely dependent on the degree of uptake by reticuloendothelial system when they are larger than 10nm. When the HD size is below 10nm, NPs show broad distribution over many organs. Reduction of HD size below the limit of renal barrier can achieve fast clearance of NPs. For maximal tumor accumulation, NPs should have long blood circulation time and should be large enough to prevent rapid penetration. NPs are also desired to rapidly clear out from the body after the mission before they cause toxic side effects. However, efficient clearance from the body to avoid side effects may result in the reduction in residence time required for accumulation in target tissues. Smart design of NP surface coating that can meet the conflicting demands can open a new avenue of NP applications. Surface charge and hydrophobicity need to be carefully considered for NP surface design. Positively charged NPs more adsorb on cell membranes and consequently show higher level of internalizations when compared with negatively charged or neutral NPs. NPs encounter a large variety of biomolecules in vivo, where non-specific adsorptions can potentially alter the physicochemical properties of the NPs. For optimal performance, NPs are suggested to have neutral surface charge at physiological conditions, small HD size, and minimal non-specific adsorption levels. Zwitterionic NP surface coating by small surface ligands can be a promising approach. Toxicity is one of most critical issues, where proper control of the NP surface can significantly reduce the toxicities.

Inorganic polymers: morphogenic inorganic biopolymers for rapid prototyping chain.

In recent years, considerable progress has been achieved towards the development of customized scaffold materials, in particular for bone tissue engineering and repair, by the introduction of rapid prototyping or solid freeform fabrication techniques. These new fabrication techniques allow to overcome many problems associated with conventional bone implants, such as inadequate external morphology and internal architecture, porosity and interconnectivity, and low reproducibility. However, the applicability of these new techniques is still hampered by the fact that high processing temperature or a postsintering is often required to increase the mechanical stability of the generated scaffold, as well as a post-processing, i.e., surface modification/functionalization to enhance the biocompatibility of the scaffold or to bind some bioactive component. A solution might be provided by the introduction of novel inorganic biopolymers, biosilica and polyphosphate, which resist harsh conditions applied in the RP chain and are morphogenetically active and do not need supplementation by growth factors/cytokines to stimulate the growth and the differentiation of bone-forming cells.

Inorganic nitrite therapy: historical perspective and future directions.

Over the past several years, investigators studying nitric oxide (NO) biology and metabolism have come to learn that the one-electron oxidation product of NO, nitrite anion, serves as a unique player in modulating tissue NO bioavailability. Numerous studies have examined how this oxidized metabolite of NO can act as a salvage pathway for maintaining NO equivalents through multiple reduction mechanisms in permissive tissue environments. Moreover, it is now clear that nitrite anion production and distribution throughout the body can act in an endocrine manner to augment NO bioavailability, which is important for physiological and pathological processes. These discoveries have led to renewed hope and efforts for an effective NO-based therapeutic agent through the unique action of sodium nitrite as an NO prodrug. More recent studies also indicate that sodium nitrate may also increase plasma nitrite levels via the enterosalivary circulatory system resulting in nitrate reduction to nitrite by microorganisms found within the oral cavity. In this review, we discuss the importance of nitrite anion in several disease models along with an appraisal of sodium nitrite therapy in the clinic, potential caveats of such clinical uses, and future possibilities for nitrite-based therapies.

Carbocyclic 6-benzylthioinosine analogues as subversive substrates of Toxoplasma gondii adenosine kinase: biological activities and selective toxicities.

Toxoplasma gondii adenosine kinase (EC 2.7.1.20) is the major route of adenosine metabolism in this parasite. The enzyme is significantly more active than any other enzyme of the purine salvage in T. gondii and has been established as a potential chemotherapeutic target for the treatment of toxoplasmosis. Several 6-benzylthioinosines have already been identified as subversive substrates of the T. gondii but not human adenosine kinase. Therefore, these compounds are preferentially metabolized to their respective nucleotides and become selectively toxic against the parasites but not its host. In the present study, we report the testing of the metabolism of several carbocyclic 6-benzylthioinosines, as well as their efficacy as anti-toxoplasmic agents in cell culture. All the carbocyclic 6-benzylthioinosine analogues were metabolized to their 5'-monophosphate derivatives, albeit to different degrees. These results indicate that these compounds are not only ligands but also substrates of T. gondii adenosine kinase. All the carbocyclic 6-benzylthioinosine analogues showed a selective anti-toxoplasmic effect against wild type parasites, but not mutants lacking adenosine kinase. These results indicate that the oxygen atom of the sugar is not critical for substrate binding. The efficacy of these compounds varied with the position and nature of the substitution on their phenyl ring. Moreover, none of these analogues exhibited host toxicity. The best compounds were carbocyclic 6-(p-methylbenzylthio)inosine (IC(50)=11.9 microM), carbocyclic 6-(p-methoxybenzylthio)inosine (IC(50)=12.1 microM), and carbocyclic 6-(p-methoxycarbonylbenzylthio)inosine (IC(50)=12.8 microM). These compounds have about a 1.5-fold better efficacy relative to their corresponding 6-benzylthioinosine analogues (Rais et al., Biochem Pharmacol 2005;69:1409-19 [29]). The results further confirm that T. gondii adenosine kinase is an excellent target for chemotherapy and that carbocyclic 6-benzylthioinosines are potential anti-toxoplasmic agents.

Designing inorganic light-protective skin nanotechnology products.

In this review, we discuss the use of inorganic nanoparticles, mainly zinc oxide (ZnO) and titanium dioxide (TiO2), for sunscreen applications considering their intrinsic physical properties and the Mie theory. These properties cause, from one side, attenuation of the ultraviolet light by absorption and scattering (dependent on a particle size), which is the purpose sunscreens are designed for, and formation of free radicals (i.e., phototoxicity) during this process--from the other. Particle penetration into skin is also an important issue addressed in this review due to possible adverse effects associated with interaction between nanoparticles and skin living cells.

Cancer imaging and therapy with metal nanoparticles.

Nanotechnology offers unique opportunities for cancer detection, therapy and the ability to monitor therapeutic interventions. This potential has to be analyzed in context of challenges that need to be overcome in translation of nanoparticles to clinical applications including specific delivery in tissues and clearance from the body. Here, we will present a case study of plasmonic nanoparticles in cancer imaging and therapy.

Traditional eye medicine use by newly presenting ophthalmic patients to a teaching hospital in south-eastern Nigeria: socio-demographic and clinical correlates.

BACKGROUND: This study set out to determine the incidence, socio-demographic, and clinical correlates of Traditional Eye Medicine (TEM) use in a population of newly presenting ophthalmic outpatients attending a tertiary eye care centre in south-eastern Nigeria. METHODS: In a comparative cross-sectional survey at the eye clinic of the University of Nigeria Teaching Hospital (UNTH), Enugu, between August 2004 - July 2006, all newly presenting ophthalmic outpatients were recruited. Participants' socio-demographic and clinical data and profile of TEM use were obtained from history and examination of each participant and entered into a pretested questionnaire and proforma. Participants were subsequently categorized into TEM- users and non-users; intra-group analysis yielded proportions, frequencies, and percentages while chi-square test was used for inter-group comparisons at P = 0.01, df = 1. RESULTS: Of the 2,542 (males, 48.1%; females, 51.9%) participants, 149 (5.9%) (males, 45%; females, 55%) used TEM for their current eye disease. The TEMs used were chemical substances (57.7%), plant products (37.7%), and animal products (4.7%). They were more often prescribed by non-traditional (66.4%) than traditional (36.9%) medicine practitioners. TEMs were used on account of vision loss (58.5%), ocular itching (25.4%) and eye discharge (3.8%). Reported efficacy from previous users (67.1%) and belief in potency (28.2%) were the main reasons for using TEM. Civil servants (20.1%), farmers (17.7%), and traders (14.1%) were the leading users of TEM. TEM use was significantly associated with younger age (p < 0.01), being married (p < 0.01), rural residence (p < 0.01), ocular anterior segment disease (p < 0.01), delayed presentation (p < 0.01), low presenting visual acuity (p < 0.01), and co-morbid chronic medical disease (p < 0.01), but not with gender (p = 0.157), and educational status (p = 0.115). CONCLUSION: The incidence of TEM use among new ophthalmic outpatients at UNTH is low. The reasons for TEM use are amenable to positive change through enhanced delivery of promotive, preventive, and curative public eye care services. This has implications for eye care planners and implementers. To reverse the trend, we suggest strengthening of eye care programmes, even distribution of eye care resources, active collaboration with orthodox eye care providers and traditional medical practitioners, and intensification of research efforts into the pharmacology of TEMs.

Inorganic materials for bone repair or replacement applications.

In recent years, excipient systems have been used increasingly in biomedicine in reconstructive and replacement surgery, as bone cements, drug-delivery vehicles and contrast agents. Particularly, interest has been growing in the development and application of controlled pore inorganic ceramic materials for use in bone-replacement and bone-repair roles and, in this context, attention has been focused on calcium-phosphate, bioactive glasses and SiO2- and TiO2-based materials. It has been shown that inorganic materials that most closely mimic bone structure and surface chemistry most closely function best in bone replacement/repair and, in particular, if a substance possesses a macroporous structure (pores and interconnections >100 microm diameter), then cell infiltration, bone growth and vascularization can all be promoted. The surface roughness and micro/mesoporosity of a material have also been observed to significantly influence its ability to promote apatite nucleation and cell attachment significantly. Pores (where present) can also be packed with pharmaceuticals and biomolecules (e.g., bone morphogenetic proteins [BMPs], which can stimulate bone formation). Finally, the most bio-efficient - in terms of collagen formation and apatite nucleation - materials are those that are able to provide soluble mineralizing species (Si, Ca, PO(4)) at their implant sites and/or are doped or have been surface-activated with specific functional groups. This article presents the context and latest advances in the field of bone-repair materials, especially with respect to the development of bioactive glasses and micro/mesoporous and macroporous inorganic scaffolds. It deals with the possible methods of preparing porous pure/doped or functionalized silicas or their composites, the studies that have been undertaken to evaluate their abilities to act as bone repair scaffolds and also presents future directions for work in that context.

[Bio-inductive effects of inorganic elements on skin wound healing].

OBJECTIVE: To explore the bio-inductive effects of inorganic elements (Dermlin) on the human epithelial proliferation and differentiation and their promoting effects on skin wound healing. METHODS: 1 ). Cellular test: Normal human skin epithelial cells were cultured with 20 g/L Dermlin supplemented culture medium (E group) and regular culture medium (C group), respectively. The cell proliferation rate and the expressions of type IV collagen and epidermal growth factor (EGF) in the supernatant were determined in 12 and 20 post culture days (PCD). (2). Animal test: Self-consubstantiality control was employed in the study. Sixty Sprague - Dawley rats were inflicted with two symmetric 10% TBSA of superficial or deep partial thickness scald on the back of each rat, and were divided into control[ C, with topical application of silver sulfadiazine (SD - Ag) cream to the wounds] and treatment (T, with 1 g/100 cm2 Dermlin topical application to the wounds) groups. The pathological changes in wound skin were observed and the wound healing rate was calculated on 3, 5, 7, 10, 14 and 18 post treatment day (PTD). (3). Randomized, double-blinded and consubstantiality control method was employed in the clinical trial. Ninety patients were enrolled in the clinical study, among them 30 cases with 60 donor site wounds, 30 with 60 superficial and 30 with 60 deep partial thickness burn wounds were included. Dermlin in dose of 1 g/100 cm2 was applied to the wounds in T group and SD - Ag cream in C group for up to 18 days. Furthermore, sixty patients with diabetic foot ulcers were included for 1 g/100 cm2 Dermlin treatment. The wound healing rate was observed. And the blood and urine test and the indices of hepatic and renal function were determined. RESULTS: 1). Cellular test: The cell proliferation rate and the expression of type IV collagen and EGF in the culture supernatant were obviously higher than those in control group at the same time points (P < 0.01). 2). Animal test: Hyperplastic granulation tissue occurred in the rat wound in the T group since 5 PTD, while that occurred in the C group since 7 PTD. The healing rate of superficial thickness wound in T group on 7, 10, 14 PTD, and that of deep partial thickness wound in T group on 5, 10, 18 PTD were obviously higher than that in the C group (P <0.05). 3). Clinical study indicated that the wound healing rate of the patients with superficial or deep partial thickness scald in the T group was evidently higher than that in the C group on 5 and 10 PTD (P <0.05), but the wound healing time of the superficial, deep partial thickness wound and donor site wound in the T group was significantly shorter than that in the C group (P < 0.05). Before treatment, the square of the ulcers on the foot of the patients with diabetic was (39 +/- 28) cm2, and it was reduced to (19 +/- 23) cm2 2 weeks later, with the therapeutic efficacy reaching 62.5% . For all patients, no obvious change was found in the blood test and hepatic and renal function indices. CONCLUSION: The inorganic element (Dermlin) is beneficial to wound healing and to the proliferation and differentiation of epithelial cells.

Gallium and other main group metal compounds as antitumor agents.

Gallium has been the second metal to show activity against malignant tumors in humans soon after the establishment of platinum drugs in routine clinical practice. It has the unique property of inhibiting tumor growth as a simple cation, mainly because of its close resemblance to ferric iron. Even though its inability to shift between the trivalent and a divalent oxidation state precludes that gallium behaves as an iron analogue in every respect, it strongly interferes with cellular acquisition of iron from blood by competitive interaction with transferrin and transferrin receptor-mediated endocytosis. Furthermore, gallium also seems to affect intracellular availability of iron already taken up via this pathway, probably due to its inhibitory activity on vacuolar-type H(+)-ATPases. Apart from the consequences of iron deprivation, gallium exerts cytotoxic effects by direct interaction with the iron-dependent enzyme ribonucleotide reductase, resulting in reduced dNTP pools and inhibition of DNA synthesis. Both the abundance of transferrin receptors and upregulation of ribonucleotide reductase render tumors susceptible to gallium-induced cytotoxicity. However, some experimental findings raise the question whether these effects resulting from the iron-mimicking properties of gallium are solely responsible for its antineoplastic activity or whether additional mechanisms are involved, such as antimitotic effects which result from its capability of inhibiting tubulin polymerization. The limitations experienced with gallium nitrate and gallium chloride, which call for a prolonged exposure to low steady-state gallium levels in blood in order to adequately exploit the affinity of gallium to tumor tissues and to avoid severe toxic effects, may be overcome by oral gallium complexes such as tris(3-hydroxy-2-methyl-4H-pyran-4-onato)gallium(III) (gallium maltolate) or tris(8-quinolinolato)gallium(III) (KP46), which are currently being evaluated in clinical trials and show promise to initiate a revival of gallium in the clinical setting. These two investigational drugs, albeit differing in their complex stability, have both been developed with the intention of providing gallium in a form which allows sufficient intestinal absorption, but without altering its pharmacodynamic effects. Gallium complexes based on other rationales are scarce and, with regard to the well-known antineoplastic potential of this metal, noticeably under-explored. With the recent approval of arsenic trioxide for the second-line treatment of acute promyelocytic leukemia, the clinical revival of arsenic compounds, which have been the mainstay of antileukemic therapy before the age of modern cancer chemotherapy, has already begun. Currently, strong efforts are being made to explore the activity spectrum in other (less rare) malignancies and to gain a deeper insight into the mode of action. Although this development is currently focusing on arsenic trioxide, it should be suited to stimulate investigations into the therapeutic potential of other arsenic compounds as well.