Fracturas atípicas de fémur asociadas al uso de bifosfonatos / Bisphosphonate associated atypical femur fractures

Resumen Los bifosfonatos son medicamentos ampliamente conocidos por su efecto antagonista de la resorción ósea y la consecuente reducción del riesgo de fracturas en los pacientes con osteoporosis. La literatura actual provee evidencia en términos de datos clínicos y experimentales que asocian el uso prolongado de estos medicamentos con un aumento en el riesgo de fracturas atípicas de fémur. Para establecer si esta asociación es clínicamente relevante, se requiere realizar estudios posteriores que incluyan la relación entre otros factores que podrían influir en la aparición de este tipo de fracturas como lo es la propia enfermedad osteoporótica, el tipo de bifosfonato utilizado, el mecanismo lesional que originó la fractura, medicamentos concomitantes y patologías asociadas.

Abstract Bisphosphonates are medications that are widely known for their antagonizing effect on bone resorption and their consequent reduction in the risk of fractures in patients with osteoporosis. Current literature provides evidence in terms of experimental and clinical data associating prolonged use of these drugs with an increase in the risk of atypical femur fractures. To establish if this association is clinically relevant, there lies a need for further studies that take into account other factors that might influence the occurrence of these type of fractures, like the osteoporotic disease itself, age, intake of other drugs and associated systemic illnesses.

Effect of particle size distribution and the filtering on the free silica measurement result by pyrophosphoric acid method / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To analyze the influence of experimental conditions: Distribution of particulate and the filter condition on the pyrophosphoric acid method for quantitative analysis of free silica in dust.</p><p><b>METHODS</b>According to Method for determination of dust in the air of workplace Part 3: Distribution of particulate (GBZ/T 192.3-2007) , Part 4: Content of free silica in dust (GBZ/T 192.4-2007) , the distribution of particulate of 5kinds of dust samples were observed. Different filter conditions were used to determinate the Content of free silica in the 4kinds ofdust samples: 1 filter paper, 2 filter papers, 3 filter papers, 2 filter papers with paper pulp in them.</p><p><b>RESULTS</b>The distribution of particulate of 4 kinds of dust sampleswere different. The order from high to low is defined with "I, II, III, IV, V" successively. For dust sample I, II, III, the results with different conditions increase successively (P<0.05) . The result in 2 filter papers with paper pulp were not significantly different compared with the reference value (P>0.05) . For dust sample IV, the resultin 1 filter paper were significantlylower thanthe reference value (P<0.05) . For dust sampleV, The results with different kinds of filter type were not significantly different (P>0.05) .</p><p><b>CONCLUSION</b>different filter conditions should be considered according to thecontent of free silica and the distribution of particulate in dust sample. For the dust sample which has the higher content of free silica and the distribution of particulate, 2 filter papers with paper pulp in themis the better filter condition compared with the traditional way.</p>

Clinical Evaluation of Residual Tetrasodium Pyrophosphate Released from Two Different Anticalculus Flosses

The aim of this study was to compare the residual content of tetrasodium pyrophosphate released by two different anticalculus dental flosses (Reach PP(r) - entangled polypropylene floss and Reach NT(r) - texturized nylon) in the oral cavity. Ten healthy individuals (aged between 18 and 30 years) were enrolled in this randomized crossover clinical investigation. Participants received instructions on daily dental flossing and the interventions were randomly performed in 2 different groups (NT or PP) of five individuals each according to the dental flosses. Individuals were instructed to use each dental floss with a total of six slides on the two interproximal aspects of target teeth (3 slides on each interproximal aspect). A washout period of one week was used before start flossing interventions and after each type of dental floss to prevent any bias related to the exposure to any product that contained the active ingredient. Samples were collected by #35 sterilized absorbent paper points from interdental fluid after flossing and assessed by ion chromatography. The levels of residual tetrasodium pyrophosphate were evaluated by means of binomial generalized linear model proportions and canonical link function. Both dental flosses were effective in tetrasodium pyrophosphate release at therapeutic levels in the interdental gingival crevicular fluid for a period of up to 2 h after use. No significant differences were found between both groups (p>0.05). It may be concluded that both material composition and physical structure of the new dental floss did not affect the release or the maintenance of anticalculus agent at therapeutic levels for a period of up to 2 h after single use.

O objetivo deste estudo foi comparar o teor residual de pirofosfato de tetrasodio liberado por dois tipos diferentes de fio dental anti-cálculo (Reach PP(r) - polipropileno entrelaçado e Reach NT(r) - nylon texturizado) na cavidade oral. Dez indivíduos saudáveis (com idade entre 18 e 30 anos) foram selecionados para este estudo clínico em modelo crossover. Os participantes receberam instruções sobre como utilizarem os fios dentais e as intervenções foram randomicamente realizadas em 2 grupos de 5 participantes de acordo com o tipo de fio avaliado. O participantes foram instruídos a passarem cada fio dental em um total de 6 passadas ao redor dos 2 espaços interproximais dos dentes selecionados (3 passadas em cada face interproximal). Um período de washout de 1 semana foi utilizado antes do início do estudo e após cada intervenção com o objetivo de prevenir a ocorrência de viés relacionado à exposição de algum agente terapêutico. Amostras do fluido interdental após as intervenções foram avaliadas por meio de cromatografia de íons. A porcentagem residual de pirofosfato tetrassódico foi verificada empregando-se o método da cromatografia de íons, pela colheita do fluido interdental com cones de papel absorvente esterilizados. Os teores de pirofosfato tetrassódico residual foram comparados para cada fio dental e para cada tempo de colheita do fluido interdental. Não foram observadas diferenças significantes entre os grupos avaliados (p>0,05). Conclui-se que a composição do material e a estrutura física dos fios dentais não exerceram influência na liberação e na permanência do agente anti-tártaro, que permaneceu em níveis terapêuticos por um período de até 2 h após o uso único.

Rapid determination of ATP, ADP, AMP and phosphate in drug by 31P NMR spectroscopy / 药学学报

The content of ATP, ADP, AMP, sodium phosphate and sodium pyrophosphate were determined by 31P NMR, the linear range of ATP, ADP and AMP were found to be 0.004-0.080 mol x L(-1), sodium phosphate and sodium pyrophosphate were 0.005-0.100 mol x L(-1). The RSD were 0.40%-1.30%, the recovery were 96.9% - 105.2%. The method has been applied to the determination of ATP injection. The impurities of ATP injection were ADP and sodium phosphate. The content of ATP is in line with the requirement of the pharmacopoeia. The results indicated that the method is of good reproducibility, high accuracy, rapid and simple operation, without pretreatment and interference of other elements, 31P NMR is a new and reliable method of analyzing ATP, ADP, AMP and phosphate.

Laboratory evaluation and field trial of activation indigenous microbial displacements in the reservoirs after polymer flooding / 生物工程学报

Most main oilfields in China have already entered a "double high" development stage (high water cut, high recovery degree). To further enhance oil recovery in reservoirs after polymer flooding (RAPFs), an efficient activator formulation for promoting metabolism of endogenous microorganism was studied by aerogenic experiments, physical simulation experiments, electron microscopy scanning and pyrophosphate sequencing. Results show that the activator could activate the endogenous microorganisms in the injected water and make the pressurized gas reach 2 MPa after 60 d static culture of the activator in a high pressure vessel. The oil recovery efficiency of natural core physical simulation flooding can be improved by more than 3.0% (OOIP) in RAPFs when injected 0.35 PV activator with 1.8% mass concentration, and a lot of growth and reproduction of activated endogenous microorganism in the core was observed by electron microscopy scanning. Field trial with 1 injector and 4 producers was carried out in the east of south II block of Sa Nan in December 2011. By monitoring four effective production wells, changes of carbon isotope δ13C (PDB) content of methane and carbon dioxide were -45 per thousand to -54 per thousand and 7 per thousand to 12 per thousand. Compared with east II of Sa Nan block, the oil amount increased by 35.9%, water cut stabled at 94%. The incremental oil was 5 957 t during the three and a half years, which provides an alternative approach for further improving oil recovery in similar reservoirs.

Iron bioavailability in Wistar rats fed with fortified rice by Ultra Rice® technology with or without addition of yacon flour (Smallanthus sonchifolius) / Biodisponibilidad de hierro en ratas Wistar alimentadas con arroz fortificado por medio de la tecnología Ultra Rice® con o sin adición de harina de yacon (Smallanthus sonchifolius).

This study aimed to evaluate iron (Fe) bioavailability in Wistar rats fed with rice fortified with micronized ferric pyrophosphate (FP) by Ultra Rice® (UR) technology with or without addition of yacon flour as a source of 7.5% of fructooligosaccharides (FOS). Diets were supplied with 12 mg iron/kg from the following sources: ferrous sulfate (FS - control diet), fortified rice with micronized ferric pyrophosphate (Ultra Rice®) (UR diet), ferrous sulfate + yacon flour (FS + Y diet) or Ultra Rice® + yacon flour (UR + Y diet). Blood samples were collected at the end of depletion and repletion stages for determination of hemoglobin concentration and calculation of the relative biological value (RBV). Also, the content of short chain fatty acids (SCFA) (acetic, propionic and butyric acids) from animals’ stools and caecum weight were determined. The UR diet showed high iron bioavailability (RBV = 84.7%). However, the addition of yacon flour in the diet containing fortified rice (UR + Y diet) decreased RBV (63.1%) significantly below the other three groups (p<0.05). Groups that received yacon flour showed higher acetic acid values compared to those who did not. In conclusion, fortified UR® with micronized ferric pyrophosphate showed high iron bioavailability but the addition of yacon flour at 7.5% FOS reduced iron bioavailability despite increased caecum weight and SCFA concentration.

Este estudio tuvo como objetivo evaluar la biodisponibilidad de hierro (Fe) en ratas Wistar alimentadas con arroz fortificado con pirofosfato férrico micronizado por medio de la tecnología Ultra Rice® (UR®), con o sin adición de harina de yacón. Las dietas contenían 12 mg de hierro/kg a partir de las siguientes fuentes: sulfato ferroso (SF - dieta de control), Ultra Rice® (dieta UR®), sulfato ferroso + harina de yacón (dieta SF + Y) o Ultra Rice® + harina de yacón (dieta UR® + Y). Al final del estudio, se recogieron muestras de sangre para la determinación de la concentración de hemoglobina y el cálculo del valor biológico relativo (RBV). También se determinó el contenido de ácidos grasos de cadena corta (AGCC) (ácidos acético, propiónico y butírico) en las heces de los animales. La dieta UR® mostró alta biodisponibilidad de hierro (RBV = 84,7%). Sin embargo, la adición de harina de yacón en la dieta que contenía arroz fortificado (dieta UR® + Y) disminuyó el RBV (63,1%) (p <0,05). Los grupos que recibieron harina de yacón mostraron los valores más altos de ácido acético en comparación con aquellos que no recibieron. En conclusión, el arroz fortificado con pirofosfato férrico micronizado por medio de la tecnología UR® mostró alta biodisponibilidad de hierro. La adición de harina de yacón, con el fin de proporcionar 7,5% de fructooligosacáridos (FOS) en la dieta, causó aumento del peso del ciego y de la concentración de AGCC, aunque disminuyó la biodisponibilidad de hierro.

Clinical evaluation of the bleaching effect of chewing gum containing amorphous calcium phosphate, hydroxyapatite, and tricalcium pyrophosphate on human enamel / 대한구강보건학회지

OBJECTIVES: The purpose of this study was to evaluate the bleaching effect of chewing gum containing amorphous calcium phosphate (ACP), hydroxyapatite (HA), and tricalcium pyrophosphate (TSP) on human enamel. METHODS: Seventy-three subjects aged 20-30 years were recruited after obtaining their informed consent and approval of the Institutional Review Board. All subjects were randomly assigned to the following four groups: (I) negative control group; (II) 50% gum group; (III) 100% gum group; and (IV) positive control group (10% carbamide peroxide). They received gum containing ACP, HA, and TSP, three times a day, for 4 weeks. Group IV also received 10% CP application using individual trays, once a day, for 2 weeks. Color change was measured using the Shade Eye-NCC colorimeter at weekly intervals, during the 4-week period. Statistical analysis was performed using SPSS 18.0. RESULTS: Color changes (DeltaE*) were significantly different among the groups at 2 and 4 weeks after chewing the gum (P<0.05). Given that bleaching effect of Group IV was 100%, bleaching effects of Group III, Group II, and Group I were 54%, 46%, and 36%, respectively. CONCLUSIONS: Chewing gum containing ACP, HA, and TSP was effective enough to bleach the human enamel. Further comprehensive studies and assessment will be required to ascertain the bleaching effects and mechanism of chewing gum containing various components such as ACP, HA, and TSP using various methods of experiment and analysis.

Exome Sequencing Reveals a Novel PRPS1 Mutation in a Family with CMTX5 without Optic Atrophy

BACKGROUND: X-linked Charcot-Marie-Tooth disease type 5 (CMTX5) is caused by mutations in the gene encoding phosphoribosyl pyrophosphate synthetase I (PRPS1). There has been only one case report of CMTX5 patients. The aim of this study was to identify the causative gene in a family with CMTX with peripheral neuropathy and deafness. CASE REPORT: A Korean family with X-linked recessive CMT was enrolled. The age at the onset of hearing loss of the male proband was 5 months, and that of steppage gait was 6 years; he underwent cochlear surgery at the age of 12 years. In contrast to what was reported for the first patients with CMTX5, this patient did not exhibit optic atrophy. Furthermore, there was no cognitive impairment, respiratory dysfunction, or visual disturbance. Assessment of his family history revealed two male relatives with very similar clinical manifestations. Electrophysiological evaluations disclosed sensorineural hearing loss and peripheral neuropathy. Whole-exome sequencing identified a novel p.Ala121Gly (c.362C>G) PRPS1 mutation as the underlying genetic cause of the clinical phenotype. CONCLUSIONS: A novel mutation of PRPS1 was identified in a CMTX5 family in which the proband had a phenotype of peripheral neuropathy with early-onset hearing loss, but no optic atrophy. The findings of this study will expand the clinical spectrum of X-linked recessive CMT and will be useful for the molecular diagnosis of clinically heterogeneous peripheral neuropathies.

Miosite ossificante progressiva: relato de caso / Myositis ossificans progressiva: case report

A miosite ossificante progressiva é uma doença rara, com menos de 1.000 casos descritos, autossômica dominante. O paciente apresenta edemas, devidos a processos inflamatórios, que vão se calcificando, com perda da mobilidade da região afetada. O objetivo deste trabalho é descrever um caso de miosite ossificante progressiva, apresentando as manifestações clínicas e discutindo os tratamentos disponíveis (ácido ascórbico oral e bifosfonato endovenoso).

Myositis Ossificans Progressiva is a rare autosomal dominant disease with less than 1,000 case reports. Such patients presents edema, caused by inflammatory processes that progressively calcify, and with loss of mobility in the region affected. The objective of this study was to describe a case of myositis ossificans progressiva, present its clinical manifestations and discuss the treatments available (oral ascorbic acid and intravenous bisphosphonate).

Characterization of recombinant single-stranded DNA-binding protein from Escherichia coli and its application in accurate pyrosequencing / 生物工程学报

We expressed recombinant single-stranded DNA-binding protein (r-SSBP) from Escherichia coli with the molecular weight of 24-kDa by using genetic engineering strategy, and demonstrated the single-stranded DNA (ssDNA)-binding activity of r-SSBP by electrophoretic mobility shift assay (EMSA). To further characterize r-SSBP, we studied the effects of r-SSBP on melting temperature (T(m)) of DNA. The results showed that r-SSBP could bind to ssDNA, and lower the T(m) of DNA, especially for single-base mismatched DNA. Therefore, r-SSBP significantly increased the T(m) difference between single-base mismatched DNA and perfect matched DNA. These results are very beneficial for single-nucleotide polymorphism detection. Moreover, we applied r-SSBP in high sensitive pyrosequencing system developed by our group. The results suggest that the r-SSBP decreased non-specific signals, corrected the proportion of signal peak height and improved the performance of pyrosequencing.

Acute Oral or Dermal and Repeated Dose 90-Day Oral Toxicity of Tetrasodium Pyrophosphate in Spraque Dawley (SD) Rats

OBJECTIVES: Tetrasodium pyrophosphate (TSP) is used in processed meat products, as an emulsifier in cheese, and as a color preservative in soybean paste. However, little is known about its toxicity. This study was conducted to investigate the potential acute and repeated dose toxicity of TSP in Spraque Dawley (SD) rats. METHODS: In the acute study, animals were administered with oral or dermal doses of 2,000 mg/kg TSP. In the repeated dose study, animals were administered doses of 0, 250, 500, and 1,000 mg/kg by oral gavage five times a week for 90 days. RESULTS: In acute toxicity studies, no dead animals or abnormal necropsy findings were found in the control or treated group. In the repeated dose toxicity study, there were no significant changes in body weight in the 1,000 mg/kg treatment group, or food consumption, urinalysis, and hematology in any group. With regards serum biochemistry, the levels of total protein, albumin, A/G ratio, triglyceride, calcium and inorganic phosphate were altered at doses of 500 and 1,000 mg/kg. However, no changes were observed at the dose of 250 mg/kg. With regards histopathological findings, cortical tubular basophilia of the kidney increased at the dose of 1,000 mg/kg, but not at doses of 250 and 500 mg/kg. No significant changes were observed in other organs at doses of 250, 500, and 1,000 mg/kg. CONCLUSIONS: Based on the results, TSP is unclassified according to the Globally Harmonization System, with an LD50 value of over 2,000 mg/kg. The no observed effect level (NOEL) and no observed adverse effect level (NOAEL) were 250 and 500 mg/kg /day respectively and the target organ appears to be the kidney.

A novel non-radioactive assay for HIV-RT (RdDp) based on pyrosequencing for high-throughput drug screening

Current in vitro assays for the activity of HIV-RT (reverse transcriptase) require radio-labeled or chemically modified nucleotides to detect reaction products. However, these assays are inherently end-point measurements and labor intensive. Here we describe a novel non-radioactive assay based on the principle of pyrosequencing coupled-enzyme system to monitor the activity of HIV-RT by indirectly measuring the release of pyrophosphate (PP(i)), which is generated during nascent strand synthesis. The results show that our assay could monitor HIV-RT activity with high sensitivity and is suitable for rapid high-throughput drug screening targeting anti-HIV therapies due to its high speed and convenience. Moreover, this assay can be used to measure primase activity in an easy and sensitive manner, which suggests that this novel approach could be wildly used to analyze the activity of PP(i)-generated and ATP-free enzyme reactions.

A Case of CPPD Crystal Deposition Disease in a Patient with Rheumatoid Arthritis and Systemic Sclerosis / 대한류마티스학회지

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is an inflammatory arthropathy that is defined by the deposition of CPPD crystals in articular and periarticular structures. CPPD crystal deposition disease has various clinical manifestation patterns ranging from an absence of symptoms to a severely destructive arthropathy. CPPD crystal deposition disease very rare with rheumatoid arthritis or systemic sclerosis. We report a case of CPPD crystal deposition disease combined in a patient with rheumatoid arthritis and systemic sclerosis.

Advances in the study of the anti-tumor activity of small molecule vascular disrupting agents / 药学学报

Vascular disrupting agents (VDAs) have presented a new kind of anti-cancer drug in recent years. VDAs take advantage of the weakness of established tumor endothelial cells and their supporting structures. In contrast to anti-angiogenic therapy, which inhibits the outgrowth of new blood vessels, vascular targeting treatments selectively attack the existing tumor vasculature. Here we summarized the anti-tumor activities, mechanisms and clinical applications of small molecule VDAs.

ENPP1 K121Q Genotype Not Associated with Coronary Artery Calcification in Korean Patients with Type 2 Diabetes Mellitus / 당뇨병

BACKGROUND: Ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) generates inorganic pyrophosphate, a solute that serves as an essential physiological inhibitor of calcification. Inactivating mutations of ENPP1 are associated with generalized calcification in infancy and an increased risk of developing type 2 diabetes mellitus (T2DM). We hypothesized that the ENPP1 K121Q variant may be associated with increased coronary artery calcification in T2DM patients. METHODS: The study subjects were aged 34 to 85 years and showed no evidence of clinical cardiovascular disease prior to recruitment. A total of 140 patients with T2DM were assessed for their coronary artery calcium (CAC) scores and ENPP1 K121Q polymorphisms were identified. RESULTS: The prevalence of subjects carrying the KQ genotype was 12.9% (n = 18). There were no 121QQ homozygotes. Patients with the KQ genotype did not show a significantly higher CAC score (122 vs. 18; P = 0.858). We matched each patient with the KQ genotype to a respective control with the KK genotype by gender, age, and duration of diabetes. When compared to matched controls, we observed no significant difference in CAC score (P = 0.959). CONCLUSIONS: The ENPP1 K121Q polymorphism does not appear to be associated with coronary artery calcification in patients with T2DM.

Idiopathic Calcium Pyrophosphate Dihydrate (CPPD) Crystal Deposition Disease in a Young Female Patient : A Case Report

PURPOSE: Calcium pyrophosphate dihydrate crystal deposition disease(CPPD) is a disease of the elderly and extremely rare in young individuals. If young people develop CPPD crystal deposition disease, it may be associated with metabolic diseases, such as hemochromatosis, hyperparathyroidism, hypophosphatasia, hypomagnesemia, Wilson's disease, hypothyroidism, and gout. MATERIALS AND METHODS: Therefore, in young-onset CPPD crystal deposition disease, an investigation of any predisposing metabolic conditions is warranted. CONCLUSION: We report a case of a young female patient who presented with idiopathic CPPD crystal deposition disease at 25 years of age.

[Management of bone density abnormalities in inflammatory bowel diseases]

Osteoporosis is a common and life-threatening problem in patient with inflammatory bowel diseases. Its management is so very important and must be systematically investigated. The incomplete comprehension of pathogenesis and physiopathology of osteopenia in IBD is source of big difficulties in the treatment of this abnormality. Many advances had been realized last years in the management of osteopenia of IBD. This paper is a review of the physiopathology of low mineral density in patients with IBD and its implications on treatment

Effects of formula fertilization to yield and content on polysaccharide of Isatis indigotica / 中国中药杂志

<p><b>OBJECTIVE</b>To select the optimum formula fertilization of Isatis indigotica through analyzing the yield and contents of polysaccharide of Radix Isatis for different treatments.</p><p><b>METHOD</b>An orthogonal experiment design on the basis of three factors and four levels was applied for studying the effect of formula fertilization on yield. The contents of polysaccharides were determined with phenol-witriolic colorimetry.</p><p><b>RESULT</b>The optimum formula fertilization of Radix Isatis was carbamide 869.0 kg x hm(-2), superphosphate 1 428.6 kg x hm(-2) and potassium sulfate 0 kg x hm(-2).</p><p><b>CONCLUSION</b>Superphosphate can observably influence the yields of Radix Inditis. while carbamide influence the contents of polysaccharide of Radix Inditis.</p>

Osteoporose pós-menopausa: opçöes terapêuticas / Postmenopausal osteoporosis: therapeutic options

O autor realizou uma revisäo na literatura sobre o tratamento atual da osteoporose pós-menopausa, abordando os principais trabalhos voltados para as drogas que efetivamente elevam a BMD e reduzem a freqüência de novas fraturas. Os estrógenos, os moduladores seletivos dos receptores de estrógenos (SERMs), os bisfosfonatos e a calcitonina foram analisados, assim como a utilizaçäo do cálcio e da vitamina D. Conclui com uma proposta de algoritmo prático de tratamento da osteoporose na pós-menopausa imediata e tardia, baseado na avaliaçäo prévia dos resultados da densitometria óssea e dos marcadores bioquímicos ósseos.