Metamagnetic Copper(II) Diphosphonates with Layered Structures

Compounds [NH3(CH2)4NH3]Cu3(hedp)2·2H2O (1) and [NH3(CH2)3NH3]Cu3(hedp)2·3.5H2O (2), where hedp represents 1-hydroxyethylidenediphosphonate, exhibit two-dimensional structures closely related to each other. The anionic layers with composition {Cu3(hedp)2}n2n- contain four- and eight-membered rings assembled from vertex-sharing {CuO4} units and {CPO3} tetrahedra. The protonated diamines and lattice water fill the interlayer spaces. Crystal data for 2:  space group P1̄, a = 8.0315(4), b = 11.3713(6), c = 13.3117(7) Å, α = 97.122(1), β = 103.187(1), γ = 108.668(1)°, V = 1095.5(1) Å3, Z = 2. Magnetic properties of the two compounds have been investigated. Both show typical metamagnetic behaviors at low temperature. The critical field at which the antiferromagnetic ground-state switches to a ferrimagnetic state is ∼48 Oe for 1 and 185 Oe for 2 at about 2 K.

Syntheses, structures and magnetic properties of two copper(Ii) diphosphonates: [NH3(CH2)2NH3]2[Cu2(hedp)2]·H2O and [NH3CH(CH3)CH2NH3]2[Cu2(hedp)2] (hedp = 1-hydroxyethylidenediphosphonate)

This paper describes the syntheses and characterization of two new copper(II) diphosphonates: [NH3(CH2)2NH3]2[Cu2(hedp)2]·H2O (1) and [NH3CH(CH3)CH2NH3]2[Cu2(hedp)2] (2) (hedp = 1-hydroxyethylidenediphosphonate). Both compounds exhibit similar one-dimensional linear chain structures. The symmetrical {Cu2(hedp)2} dimers are connected by edge-shared {CuO5} square pyramids and form infinite chains. The Cu(II) ions are alternately bridged by O–P–O groups and O atoms. The Cu–O–Cu angles are 95.8(1) and 96.1(1)° for 1 and 2, respectively. Their magnetic properties show moderately strong antiferromagnetic interactions in both compounds.

Chemotherapy and zoledronate sensitize solid tumour cells to Vγ9Vδ2 T cell cytotoxicity

Combinations of cellular immune-based therapies with chemotherapy and other antitumour agents may be of significant clinical benefit in the treatment of many forms of cancer. Gamma delta (γδ) T cells are of particular interest for use in such combined therapies due to their potent antitumour cytotoxicity and relative ease of generation in vitro. Here, we demonstrate high levels of cytotoxicity against solid tumour-derived cell lines with combination treatment utilizing Vγ9Vδ2 T cells, chemotherapeutic agents and the bisphosphonate, zoledronate. Pre-treatment with low concentrations of chemotherapeutic agents or zoledronate sensitized tumour cells to rapid killing by Vγ9Vδ2 T cells with levels of cytotoxicity approaching 90%. In addition, zoledronate enhanced the chemotherapy-induced sensitization of tumour cells to Vγ9Vδ2 T cell cytotoxicity resulting in almost 100% lysis of tumour targets in some cases. Vγ9Vδ2 T cell cytotoxicity was mediated by perforin following TCR-dependent and isoprenoid-mediated recognition of tumour cells. Production of IFN-γ by Vγ9Vδ2 T cells was also induced after exposure to sensitized targets. We conclude that administration of Vγ9Vδ2 T cells at suitable intervals after chemotherapy and zoledronate may substantially increase antitumour activities in a range of malignancies.

Management of fragility fractures in Switzerland: results of a nationwide survey.

A nationwide survey was conducted in Switzerland to assess the quality level of osteoporosis management in patients aged 50 years or older presenting with a fragility fracture to the emergency ward of the participating hospitals. Eight centres recruited 4966 consecutive patients who presented with one or more fractures between 2004 and 2006. Of these, 3667 (2797 women, 73.8 years old and 870 men, 73.0 years old in average) were considered as having a fragility fracture and included in the survey. Included patients presented with a fracture of the upper limbs (30.7%), lower limbs (26.4%), axial skeleton (19.5%) or another localisation, including malleolar fractures (23.4%). Thirty-two percent reported one or more previous fractures during adulthood. Of the 2941 (80.2%) hospitalised women and men, only half returned home after discharge. During diagnostic workup, dual x-ray absorptiometry (DXA) measurement was performed in 31.4% of the patients only. Of those 46.0% had a T-score < or =-2.5 SD and 81.1% < or =-1.0 SD. Osteoporosis treatment rate increased from 26.3% before fracture to 46.9% after fracture in women and from 13.0% to 30.3% in men. However, only 24.0% of the women and 13.8% of the men were finally adequately treated with a bone active substance, generally an oral bisphosphonate, with or without calcium / vitamin D supplements. A positive history of previous fracture vs none increased the likelihood of getting treatment with a bone active substance (36.6 vs 17.9%, ? 18.7%, 95% CI 15.1 to 22.3, and 22.6 vs 9.9%, ? 12.7%, CI 7.3 to 18.5, in women and men, respectively). In Switzerland, osteoporosis remains underdiagnosed and undertreated in patients aged 50 years and older presenting with a fragility fracture.

Effect of zoledronic acid used in the root surface treatment of late replanted teeth: A study in rats

This study evaluated the use of zoledronic acid, a resorption inhibitor, as a medication for root resorption treatment of late replanted teeth. Twenty-four maxillary right central incisors of rats were avulsed and kept dry for 30 min. Then, the teeth were divided into 2 groups. In group I, root surface was treated with 2% sodium fluoride for 20 min; in group II, 10-6M zoledronic acid solution was used for 20 min. All root canals were filled with calcium hydroxide. Next, teeth were replanted in their respective sockets. After 15 and 60 days post-replantation, the animals were killed and the anatomic pieces were obtained and prepared for microscopic and morphometric analyses. The results showed that zoledronic acid was capable of limiting the occurrence of root resorption and preserving cementum resorption. Further research must be performed to confirm the use of zoledronic acid in root surface treatment of late replanted teeth.

Effects of zoledronic acid on odontoblast-like cells

The aim of the study was to evaluate the effects of a highly potent bisphosphonate, zoledronic acid (ZOL), on cultured odontoblast-like cells MDPC-23. The cells (1.5 × 104 cells/cm2) were seeded for 48 h in wells of 24-well dished. Then, the plain culture medium (DMEM) was replaced by fresh medium without fetal bovine serum. After 24 h, ZOL (1 or 5 μM) was added to the medium and maintained in contact with the cells for 24 h. After this period, the succinic dehydrogenase (SDH) enzyme production (cell viability-MTT assay), total protein (TP) production, alkaline phosphatase (ALP) activity, and gene expression (qPCR) of collagen type I (Col-I) and ALP were evaluated. Cell morphology was assessed by SEM. Five μM ZOL caused a significant decrease in SDH production. Both ZOL concentrations caused a dose-dependent significant decrease in TP production and ALP activity. ZOL also produced discret morphological alterations in the MDPC-23 cells. Regarding gene expression, 1 μM ZOL caused a significant increase in Col-I expression. Although 5 μM ZOL did not affect Col-I expression, it caused a significant alteration in ALP expression (ANOVA and Tukey's test, p < 0.05). ZOL presented a dose-dependent cytotoxic effect on the odontoblast-like cells, suggesting that under clinical conditions the release of this drug from dentin could cause damage to the pulpo-dentin complex. © 2012 Elsevier Ltd.

Efeitos da Calcarea phosphorica 6CH e do alendronato na reparação da lesão óssea em ratas ovariectomizadas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Effects of Locally Administered Tiludronic Acid on Experimental Periodontitis in Rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Diretrizes para prevenção e tratamento da osteoporose induzida por glicocorticoide

Os glicocorticoides (GC) são prescritos por praticamente todas as especialidades médicas, e cerca de 0,5% da população geral do Reino Unido utiliza esses medicamentos. Com o aumento da sobrevida dos pacientes com doenças reumatológicas, a morbidade secundária ao uso dessa medicação representa um aspecto importante que deve ser considerado no manejo de nossos pacientes. As incidências de fraturas vertebrais e não vertebrais são elevadas, variando de 30%-50% em pessoas que usam GC por mais de três meses. Assim, a osteoporose e as fraturas por fragilidade devem ser prevenidas e tratadas em todos os pacientes que iniciarão ou que já estejam em uso desses esteroides. Diversas recomendações elaboradas por várias sociedades internacionais têm sido descritas na literatura, porém não há consenso entre elas. Recentemente, o Americam College of Rheumatology publicou novas recomendações, porém elas são fundamentadas na FRAX (WHO Fracture Risk Assessment Tool) para analisar o risco de cada indivíduo e, dessa maneira, não podem ser completamente utilizadas pela população brasileira. Dessa forma, a Comissão de Osteoporose e Doenças Osteometabólicas da Sociedade Brasileira de Reumatologia, em conjunto com a Associação Médica Brasileira e a Associação Brasileira de Medicina Física e Reabilitação, implementou as diretrizes brasileiras de osteoporose induzida por glicocorticoide (OPIG), baseando-se na melhor evidência científica disponível e/ou experiência de experts. DESCRIÇÃO DO MÉTODO DE COLETA DE EVIDÊNCIA: A revisão bibliográfica de artigos científicos desta diretriz foi realizada na base de dados MEDLINE. A busca de evidência partiu de cenários clínicos reais, e utilizou as seguintes palavras-chave (MeSH terms): Osteoporosis, Osteoporosis/chemically induced*= (Glucocorticoids= Adrenal Cortex Hormones, Steroids), Glucocorticoids, Glucocorticoids/administration and dosage, Glucocorticoids/therapeutic use, Glucocorticoids/adverse effects, Prednisone/adverse effects, Dose-Response Relationship, Drug, Bone Density/drug effects, Bone Density Conservation Agents/pharmacological action, Osteoporosis/ prevention&control, Calcium, Vitamin D, Vitamin D deficiency, Calcitriol, Receptors, Calcitriol; 1-hydroxycholecalciferol, Hydroxycholecalciferols, 25-Hydroxyvitamin D3 1-alpha-hydroxylase OR Steroid Hydroxylases, Prevention and Control, Spinal fractures/prevention & control, Fractures, Spontaneous, Lumbar Vertebrae/injuries, Lifestyle, Alcohol Drinking, Smoking OR tobacco use disorder, Movement, Resistance Training, Exercise Therapy, Bone density OR Bone and Bones, Dual-Energy X-Ray Absorptiometry OR Absorptiometry Photon OR DXA, Densitometry, Radiography, (Diphosphonates Alendronate OR Risedronate Pamidronate OR propanolamines OR Ibandronate OR Zoledronic acid, Teriparatide OR PTH 1-34, Men AND premenopause, pregnancy, pregnancy outcome maternal, fetus, lactation, breast-feeding, teratogens, Children (6-12 anos), adolescence (13-18 anos). GRAU DE RECOMENDAÇÃO E FORÇA DE EVIDÊNCIA: A) Estudos experimentais e observacionais de melhor consistência; B) Estudos experimentais e observacionais de menor consistência; C) Relatos de casos (estudos não controlados); D) Opinião desprovida de avaliação crítica, com base em consensos, estudos fisiológicos ou modelos animais. OBJETIVO: Estabelecer as diretrizes para a prevenção e o tratamento da OPIG.

Bisphosphonates for metastatic bone disease in lung cancer

Bisphosphonates have proven effectiveness in preventing skeletal-related events (SREs) in advanced breast cancer, prostate cancer and multiple myeloma. The purpose of this study was to assess efficacy of bisphosphonates in preventing SREs, in controlling pain, and in increasing life expectancy in lung cancer patients with bone metastases.^ We performed an electronic search in MEDLINE, EMBASE, Web of Science, and Cochrane library databases up to April 4, 2010. Hand searching and searching in clinicaltrials.gov were also performed. Two independent reviewers selected all clinical trials that included lung cancer patients with bone metastases treated with bisphosphonates. We excluded articles that involved cancers other than lung, patients without bone metastasis and treatment other than bisphosphonates. Outcome questions answered were efficacy measured as overall pain control, overall improvement in survival and reduction in skeletal-related events or SREs (fracture, cord compression, radiation or surgery to the bone, hypercalcemia of malignancy). The quality of each study was evaluated using the Cochrane Back Review group questionnaire to assess risk of bias (0-worst to 11-best). Data extraction and quality assessments were independently performed by two assessors. Meta-analyses were performed where more than one study with similar outcomes were found.^ We identified eight trials that met our inclusion criteria. Three studies evaluated zoledronic acid, three pamidronate, three clodronate and two ibandronate. Two were placebocontrol trials while two had multi-group comparisons (radiotherapy, radionucleotides, and chemotherapy) and two had different bisphosphonate as active controls. Quality scores ranged from 1-4 out of 11 suggesting high risk of bias. Studies failed to report adequate explanation of randomization procedures, concealment of randomization and blinding. Metaanalysis showed that patients treated with zoledronic acid alone had lower rates of developing SREs compared to placebo at 21 months (RR=0.80, 95% CI=0.66-0.97, p=0.02). Meta-analyses also showed increased pain control when a bisphosphonate was added to the existing treatment modality like chemotherapy or radiation (RR=1.17, 95% CI=1.03-1.34, p=0.02). However, pain control was not statistically significantly different among various bisphosphonates when other treatment modalities were not present. Despite improvement in SRE and pain control, bisphosphonates failed to show improvement in overall survival (Difference in means=109.1 days, 95% CI= -51.52 – 269.71, p=0.183).^ Adding biphosphonates to standard care improved pain control and reduced SREs. Biphosphonates did not improve overall survival. Further larger studies with higher quality are required to stengthen the evidence.^ Keywords/MeSH terms Bisphosphonates/diphosphonates: generic, chemical and trade names.^

Fracionamento de kits de HMDP para marcação com 99mTc: influência da temperatura e da idade das frações

Mestrado em Medicina Nuclear - Área de especialização: Radiofarmácia