Ultrasound power delivery can be considered a convenient technique for charging implantable medical devices. In this work, an intra-body system has been modeled to characterize the phenomenon of ultrasound power transmission. The proposed system comprises a Langevin transducer as transmitter and an AlN-based square piezoelectric micro-machined ultrasonic transducer as receiver. The medium layers, in which elastic waves propagate, were made by polydimethylsiloxane to mimic human tissue and stainless steel to replace the case of the implantable device. To characterize the behavior of the transducers, measurements of impedance and phase, velocity and displacement, and acoustic pressure field were carried out in the experimental activity. Then, voltage and power output were measured to analyze the performance of the ultrasound power delivery system. For a root mean square voltage input of approximately 35 V, the power density resulted in 21.6 μW cm-2. Such a result corresponds to the data obtained with simulation through a one-dimensional lumped parameter transmission line model. The methodology proposed to develop the ultrasound power delivery (UPD) system, as well as the use of non-toxic materials for the fabrication of the intra-body elements, are a valid design approach to raise awareness of using wireless power transfer techniques for charging implantable devices.
- Publikační typ
- časopisecké články MeSH
Systemic administration of bisphosphonates, e.g. sodium alendronate (Aln) is characterized by extremely low bioavailability and high toxicity. To omit aforementioned drawbacks an injectable system for the intra-bone delivery of Aln based on Aln-loaded nanoparticles (NPs-Aln) suspended in a hydrogel matrix (gellan gum, GG) was developed. Aln was encapsulated in poly(lactide-co-glycolide) (PLGA 85:15) by solid-oil-water emulsification. Drug release tests showed that within 25 days all the encapsulated drug was released from NPs-Aln and the release rate was highest at the beginning and decreased with time. In contrast, by suspending NPs-Aln in a GG matrix, the release rate was significantly lower and more constant in time. The GG-NPs-Aln system was engineered to be easily injectable and was able to reassemble its structure after extrusion as shown by rheological measurements. Invitro studies showed that the GG-NPs-Aln was cytocompatible with MG-63 osteoblast-like cells and it inhibited RANKL-mediated osteoclastic differentiation of RAW 264.7 cells. The injectability, the sustained local delivery of small doses of Aln and the biological activity render the GG-NPs-Aln system promising for the local treatment of osteoporosis and other bone tissue disorders.
- MeSH
- alendronát aplikace a dávkování chemie MeSH
- bakteriální polysacharidy chemie MeSH
- buněčná diferenciace účinky léků MeSH
- farmaceutická chemie MeSH
- farmaceutická technologie metody MeSH
- hydrogely MeSH
- inhibitory kostní resorpce aplikace a dávkování chemie MeSH
- injekce MeSH
- kinetika MeSH
- kyselina mléčná chemie MeSH
- kyselina polyglykolová chemie MeSH
- lidé MeSH
- ligand RANK farmakologie MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nanočástice * MeSH
- nanotechnologie MeSH
- nosiče léků * MeSH
- osteoblasty účinky léků metabolismus MeSH
- osteoklasty účinky léků metabolismus MeSH
- RAW 264.7 buňky MeSH
- reologie MeSH
- rozpustnost MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Bisphosphonates (BPs) are compounds resembling the pyrophosphate structure. BPs bind the mineral component of bones. During the bone resorption by osteoclasts, nitrogen-containing BPs are released and internalized, causing an inhibition of the mevalonate pathway. As a consequence, osteoclasts are unable to execute their function. Alendronate (ALN) is a bisphosphonate used to treat osteoporosis. Its administration could be associated with adverse effects. The purpose of this study is to evaluate four different ALN concentrations, ranging from 10-6 to 10-10 M, in the presence of different combinations of M-CSF and RANKL, to find out the effect of low ALN concentrations on osteoclastogenesis using rat and human peripheral blood mononuclear cells. The cytotoxic effect of ALN was evaluated based on metabolic activity and DNA concentration measurement. The alteration in osteoclastogenesis was assessed by the activity of carbonic anhydrase II (CA II), tartrate-resistant acid phosphatase staining, and actin ring formation. The ALN concentration of 10-6 M was cytotoxic. Low ALN concentrations of 10-8 and 10-10 M promoted proliferation, osteoclast-like cell formation, and CA II activity. The results indicated the induction of osteoclastogenesis with low ALN concentrations. However, when high doses of ALN were administered, their cytotoxic effect was demonstrated.
- MeSH
- aktiny metabolismus MeSH
- alendronát farmakologie MeSH
- barvení a značení MeSH
- DNA metabolismus MeSH
- faktor stimulující kolonie makrofágů farmakologie MeSH
- karboanhydrasa II metabolismus MeSH
- krysa rodu rattus MeSH
- kyselá fosfatasa rezistentní k tartarátu metabolismus MeSH
- leukocyty mononukleární účinky léků metabolismus MeSH
- lidé MeSH
- ligand RANK farmakologie MeSH
- osteogeneze účinky léků MeSH
- osteoklasty účinky léků enzymologie metabolismus MeSH
- proliferace buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Cortical bone, the dominant component of the human skeleton by volume, plays a key role in protecting bones from fracture. We analyzed the cortical bone effects of teriparatide treatment in postmenopausal women with osteoporosis who had previously received long-term alendronate (ALN) therapy or were treatment naïve (TN). Tetracycline-labeled paired iliac crest biopsies obtained from 29 ALN-pretreated and 16 TN women were evaluated for dynamic histomorphometric parameters of bone formation at the periosteal, endocortical and intracortical bone compartments, before and after 24months of teriparatide treatment. At baseline, the frequency of specimens without any endocortical and periosteal tetracycline labeling, and the percentage of quiescent osteons, was higher in the ALN than the TN group. Endocortical and periosteal mineralizing surface (MS/BS%), periosteal bone formation rate (BFR/BS), mineral apposition rate (MAR) and the number of intracortical forming osteons were significantly lower in the ALN-pretreated patients than in the TN group. Following teriparatide treatment, the frequency of endocortical and periosteal unlabeled biopsies decreased; in the ALN-pretreated group the percentage of quiescent osteons decreased and, in contrast, forming and resorbing osteons were increased. Teriparatide treatment resulted in significant increases of MAR in the endocortical, and MS/BS% in the periosteal compartment in the ALN-pretreated group. Most indices of bone formation remained lower in the ALN-pretreated group compared with the TN group at study end. Endocortical wall width was increased in both ALN-pretreated and TN groups. Cortical porosity and cortical thickness were significantly increased in the ALN-pretreated group after teriparatide treatment. Our results suggest that 24months of teriparatide treatment increases cortical bone formation and cortical turnover in patients who were either TN or had previous ALN therapy.
- MeSH
- alendronát farmakologie terapeutické užití MeSH
- fyziologická kalcifikace účinky léků MeSH
- lidé MeSH
- osteogeneze účinky léků MeSH
- postmenopauzální osteoporóza farmakoterapie patofyziologie MeSH
- senioři MeSH
- teriparatid farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
PURPOSE: Osteoporosis is a severe health problem with social and economic impacts on society. The standard treatment consists of the systemic administration of drugs such as bisphosphonates, with alendronate (ALN) being one of the most common. Nevertheless, complications of systemic administration occur with this drug. Therefore, it is necessary to develop new strategies, such as local administration. METHODS: In this study, emulsion/dispersion scaffolds based on W/O emulsion of PCL and PF68 with ALN, containing hydroxyapatite (HA) nanoparticles as the dispersion phase were prepared using electrospinning. Scaffolds with different release kinetics were tested in vitro on the co-cultures of osteoblasts and osteoclast-like cells, isolated from adult osteoporotic and control rats. Cell viability, proliferation, ALP, TRAP and CA II activity were examined. A scaffold with a gradual release of ALN was tested in vivo in the bone defects of osteoporotic and control rats. RESULTS: The release kinetics were dependent on the scaffold composition and the used system of the poloxamers. The ALN was released from the scaffolds for more than 22 days. The behavior of cells cultured in vitro on scaffolds with different release kinetics was comparable. The difference was evident between cell co-cultures isolated from osteoporotic and control animals. The PCL/HA scaffold show slow degradation in vivo and residual scaffold limited new bone formation inside the defects. Nevertheless, the released ALN supported bone formation in the areas surrounding the residual scaffold. Interestingly, a positive effect of systemic administration of ALN was not proved. CONCLUSION: The prepared scaffolds enabled tunable control release of ALN. The effect of ALN was proved in vitro and in in vivo study supported peri-implant bone formation.
- MeSH
- alendronát * farmakologie MeSH
- emulze farmakologie MeSH
- hydroxyapatit farmakologie MeSH
- inhibitory kostní resorpce * farmakologie MeSH
- krysa rodu rattus MeSH
- osteoblasty MeSH
- osteogeneze MeSH
- osteoklasty MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The aim of this study was to assess the effects of the antiresorptive treatments of alendronate (ALN), risedronate (RIS) and raloxifene (RLX) on the response of bone to endogenous parathyroid hormone (PTH) induced by acute hypocalcemia. Forty women (age, 55-80 years) with postmenopausal osteoporosis (treated with ALN, RIS and RLX or untreated-control group) were given infusions of sodium ethylenediaminetetraacetic acid (EDTA; 10 mg/kg of body weight). Serum ionized calcium (iCa), plasma intact PTH and marker of bone resorption, serum beta C-terminal telopeptide of type I collagen (beta-CTX; beta CrossLaps) were followed for 180 min. In all women, decrease in serum iCa following the EDTA load resulted in an acute increase in serum PTH. Between 60 and 180 min, plasma PTH in the ALN and RIS treated women remained significantly higher than in the control group. The integrated beta-CTX responses (area under curves, AUCs) to peaks of PTH were significantly lower in the ALN treated women than in those treated with RIS, RLX or control group. There was no significant difference in beta-CTX AUC response to PTH between RIS, RLX and control women. Taken together, these findings suggest that in women with postmenopausal osteoporosis treated with ALN, a substantial reduction of bone turnover blunts the acute bone resorbing effect of endogenous PTH.
- MeSH
- alendronát terapeutické užití MeSH
- biologické markery krev MeSH
- chelátory farmakologie MeSH
- EDTA farmakologie MeSH
- financování organizované MeSH
- hypokalcemie chemicky indukované MeSH
- inhibitory kostní resorpce terapeutické užití MeSH
- kolagen typu I účinky léků MeSH
- kyselina etidronová analogy a deriváty terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- parathormon metabolismus MeSH
- peptidy účinky léků MeSH
- plocha pod křivkou MeSH
- postmenopauzální osteoporóza farmakoterapie krev MeSH
- raloxifen hydrochlorid terapeutické užití MeSH
- remodelace kosti účinky léků MeSH
- resorpce kosti metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
Marked suppression of bone turnover by bisphosphonates is associated with increased bone microdamage accumulation in animal models. The purpose of this study was to test the hypothesis that long-term treatment with alendronate (ALN) results in accumulation of microdamage in bone in women after menopause. Sixty-six postmenopausal women with osteoporosis (mean age of 68.0 years and mean BMD T-score of -1.7 at total hip and -2.8 at lumbar spine; 62% with prevalent fractures) were evaluated in this cross-sectional analysis. Thirty-eight had been treated previously with ALN (10 mg/day or 70 mg/week for a mean duration of 63.6 months) while twenty-eight were treatment naive (TN). Without adjustments, crack surface density (Cr.S.Dn) and crack density (Cr.Dn) were not different between ALN and TN patients. After adjustment for potential confounders (age, prevalent fractures, femoral neck BMD, activation frequency and center), Cr.Dn was elevated in ALN patients (P=0.028 and P=0.069 for Cr.S.Dn). In ALN patients only, lower femoral neck BMD (Cr.S.Dn, r=-0.58, P=0.003; Cr.Dn, r=-0.54, P=0.005) and increased age (Cr.S.Dn, r=0.43, P=0.03; Cr.Dn, r=0.43, P=0.03) were associated with microdamage accumulation. Among potential confounders, femoral neck BMD was the only independent predictor for these correlations (P=0.04 for Cr.Dn and P=0.03 for Cr.S.Dn). We conclude that increased microdamage accumulation may occur in low BMD patients treated with alendronate.
- MeSH
- alendronát škodlivé účinky MeSH
- inhibitory kostní resorpce škodlivé účinky MeSH
- kosti a kostní tkáň patologie účinky léků MeSH
- kostní denzita fyziologie účinky léků MeSH
- lidé MeSH
- postmenopauza MeSH
- postmenopauzální osteoporóza farmakoterapie MeSH
- průřezové studie MeSH
- senioři MeSH
- věkové faktory MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- klinické zkoušky MeSH
- multicentrická studie MeSH
The level of increased bone formation after 24 months of treatment with teriparatide (rhPTH (1-34), TPTD) is similar in patients who were either treatment-naïve (TN) or had lower bone turnover initially due to previous alendronate (ALN) therapy. INTRODUCTION: Bone anabolic effects of TPTD in postmenopausal women with osteoporosis may be blunted during the initial phase after switching from ALN to TPTD. To explore the long-term implications, we examined histomorphometric and biochemical markers of bone turnover of patients on TPTD therapy after long-term ALN treatment. METHODS: Paired biopsies were obtained after tetracycline double labeling at baseline and after 24 months of TPTD treatment from 29 ALN-pretreated (64.5 ± 16.4 months) and 16 TN patients. Biochemical markers were measured at baseline, during the treatment, or at study end. RESULTS: Compared with the baseline, after 24-month TPTD, activation frequency (Ac.F.) and osteoid surface (OS) increased in both groups: 0.11-0.34 cycles per year, 3.96-9.8% in the ALN-pretreated group and 0.19-0.33 cycles per year, 6.2-11.3% (p < 0.05) in the TN group, respectively. Biochemical and histomorphometric markers correlated positively both at baseline and endpoint. Serum amino terminal propeptide of type I procollagen (PINP) correlated with Ac.F. (r = 0.57, p < 0.001 and r = 0.48, p < 0.01) and OS (r = 0.51, p < 0.01 and r = 0.56, p < 0.01) at baseline and endpoint, respectively. Following 3 months of treatment, increases in biochemical markers like PINP predicted the increase in Ac.F. (r = 0.52, p < 0.01) and OS (r = 0.54, p < 0.01) after 24 months. CONCLUSIONS: The increased level of formation is similar in patients who were either TN or had lower bone turnover initially due to previous ALN therapy. Elevated bone formation in postmenopausal women with osteoporosis was sustained over a 24-month period by TPTD. Biochemical markers of bone formation are a good surrogate for the assessment of TPTD effects.
- MeSH
- alendronát terapeutické užití MeSH
- bederní obratle patofyziologie MeSH
- biologické markery krev MeSH
- biopsie MeSH
- dospělí MeSH
- inhibitory kostní resorpce terapeutické užití MeSH
- kostní denzita účinky léků MeSH
- krček femuru patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- náhrada léků MeSH
- osteogeneze účinky léků MeSH
- postmenopauzální osteoporóza farmakoterapie patologie patofyziologie MeSH
- remodelace kosti účinky léků MeSH
- senioři MeSH
- teriparatid terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky kontrolované MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
Laser Desorption Ionisation (LDI) and Matrix-Assisted Laser Desorption Ionisation (MALDI) Time-of-Flight Mass Spectrometry (TOFMS) were used to study the pulsed laser ablation of aluminium nitride (AlN) nano powder. The formation of Al(m)(+) (m=1-3), N(n)(+) (n=4, 5), AlN(n)(+) (n=1-5, 19, 21), Al(m)N(+) (m=2-3), Al(3)N(2)(+), Al(9)N(n)(+) (n=5, 7, 9, 11 and 15), Al(11)N(n)(+) (n=4, 6, 10, 12, 19, 21, 23, and 25), and Al(13)N(n)(+) (n=25, 31, 32, 33, 34, 35, and 36) clusters was detected in positive ion mode. Similarly, Al(m)(-) (m=1-3), AlN(n)(-) (n=1-3, 5), Al(m)N(-) (n=2, 3), Al(2)N(n)(-) (n=2-4, 28, 30), N(n)(-) (n=2, 3), Al(4)N(7)(-) Al(8)N(n)(-) (n=1-6), and Al(13)N(n)(-) (n=9, 18, 20, 22, 24, 26, 28, 33, 35, 37, 39, 41 and 43) clusters were observed in negative ion mode. The formation of the stoichiometric Al(10) N(10) cluster was shown to be of low abundance. On the contrary, the laser ablation of nano-AlN led mainly to the formation of nitrogen-rich Al(m)N(n) clusters in both negative and positive ion mode. The stoichiometry of the Al(m)N(n) clusters was determined via isotopic envelope analysis and computer modelling.
- Publikační typ
- časopisecké články MeSH
[Extraction of caval filter 7 years after placement]
Plicní embolie je závažné, mnohdy život ohrožující postižení kardiovaskulárního systému. Jako prevence plicní embolie se kromě medikamentózní terapie provádí také implantace kaválního filtru do dolní duté žíly. Představuje mechanickou překážku pro průnik krevních sraženin do plic. Předkládáme kazuistiku nemocné, které byl ALN kavální filtrimplantován před 7 lety po porodu, kdy byl prokázán vlající trombus v dolní duté žíle, trombus zasahoval až k odstupu pravé rená lni žíly. Proto byl filtrimplantován atypicky nad odstupy renálních žil. Sedm let po implantaci kaválního filtru přichází pacientka s neurčitými bolestmi v pravém podžebří k vyšetření. Protože nebezpečí plicní embolie pominulo, bylo rozhodnuto pokusit se o endovaskulámí odstranění tohoto filtru. Filtr byl úspěšně odstraněn, výkon proběhl bez komplikací, jen bylo nutné použít o 1 F větší sheath, nežje doporučeno, což lze patrně vysvětlit tím, že po dlouhé době implantace byly kotvící nožičky filtru potaženy fibrinem. Popisovaná kazuistika patří k případům, kde byl kavální filtr úspěšně odstraněn po poměrně dlouhé době po implantaci.
Pulmonary embolia is serious, often life threatening disease. As a pulmonary embolia prevention anticoagulation therapy is usually used, but in some cases inferior vena cava filter placement is employed. Filter creates a mechanical barrier preventing the passage of the embolus into lungs. We present a case of female patient with ALN caval filter placed 7 years ago after child delivery. She had floating thrombus in inferior vena cava, the top of the thrombus was up to ostium of right renal vein. It was the reason why the filter was placed atypically above renal veins level. Seven years after filter placement the patient complains on non-specific pain in right upper abdominal area. As the risk of pulmonary embolia is not present anymore it was decided to remove the filter by endovascular approach. The filter removal was successful and was complication-free. We had to use a sheath 1 F larger than recommended, most probably due to fibrin coating of the filter anchoring struts. Presented case belongs to the few presented case reports when the filter was removed after relatively long time after placement.
- Klíčová slova
- kavografie,
- MeSH
- dospělí MeSH
- kavální filtry * škodlivé účinky MeSH
- lidé MeSH
- plicní embolie terapie MeSH
- počítačová rentgenová tomografie MeSH
- tromboembolie terapie MeSH
- vena cava inferior diagnostické zobrazování patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH