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1.
Infect Dis Model ; 8(1): 183-191, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36643865

ABSTRACT

Recently some of us used a random-walk Monte Carlo simulation approach to study the spread of COVID-19. The calculations were reasonably successful in describing secondary and tertiary waves of infection, in countries such as the USA, India, South Africa and Serbia. However, they failed to predict the observed third wave for India. In this work we present a more complete set of simulations for India, that take into consideration two aspects that were not incorporated previously. These include the stochastic movement of an erstwhile protected fraction of the population, and the reinfection of some recovered individuals because of their exposure to a new variant of the SARS-CoV-2 virus. The extended simulations now show the third COVID-19 wave for India that was missing in the earlier calculations. They also suggest an additional fourth wave, which was indeed observed during approximately the same time period as the model prediction.

2.
Chaos Solitons Fractals ; 156: 111785, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35035125

ABSTRACT

Phenomenological and deterministic models are often used for the estimation of transmission parameters in an epidemic and for the prediction of its growth trajectory. Such analyses are usually based on single peak outbreak dynamics. In light of the present COVID-19 pandemic, there is a pressing need to better understand observed epidemic growth with multiple peak structures, preferably using first-principles methods. Along the lines of our previous work  [Physica A 574, 126014 (2021)], here we apply 2D random-walk Monte Carlo calculations to better understand COVID-19 spread through contact interactions. Lockdown scenarios and all other control interventions are imposed through mobility restrictions and a regulation of the infection rate within the stochastically interacting population. The susceptible, infected and recovered populations are tracked over time, with daily infection rates obtained without recourse to the solution of differential equations. The simulations were carried out for population densities corresponding to four countries, India, Serbia, South Africa and USA. In all cases our results capture the observed infection growth rates. More importantly, the simulation model is shown to predict secondary and tertiary waves of infections with reasonable accuracy. This predictive nature of multiple wave structures provides a simple and effective tool that may be useful in planning mitigation strategies during the present pandemic.

3.
Epidemics ; 37: 100515, 2021 12.
Article in English | MEDLINE | ID: mdl-34763160

ABSTRACT

BACKGROUND: Recent work showed that the temporal growth of the novel coronavirus disease (COVID-19) follows a sub-exponential power-law scaling whenever effective control interventions are in place. Taking this into consideration, we present a new phenomenological logistic model that is well-suited for such power-law epidemic growth. METHODS: We empirically develop the logistic growth model using simple scaling arguments, known boundary conditions and a comparison with available data from four countries, Belgium, China, Denmark and Germany, where (arguably) effective containment measures were put in place during the first wave of the pandemic. A non-linear least-squares minimization algorithm is used to map the parameter space and make optimal predictions. RESULTS: Unlike other logistic growth models, our presented model is shown to consistently make accurate predictions of peak heights, peak locations and cumulative saturation values for incomplete epidemic growth curves. We further show that the power-law growth model also works reasonably well when containment and lock down strategies are not as stringent as they were during the first wave of infections in 2020. On the basis of this agreement, the model was used to forecast COVID-19 fatalities for the third wave in South Africa, which was in progress during the time of this work. CONCLUSION: We anticipate that our presented model will be useful for a similar forecasting of COVID-19 induced infections/deaths in other regions as well as other cases of infectious disease outbreaks, particularly when power-law scaling is observed.


Subject(s)
COVID-19 , Belgium , Communicable Disease Control , Humans , SARS-CoV-2 , South Africa
4.
Biomed Microdevices ; 23(2): 26, 2021 04 22.
Article in English | MEDLINE | ID: mdl-33885989

ABSTRACT

A continuous rise in the wastes from industrial effluents, bio-waste, and pharmaceuticals has deteriorated surface water and drinking water sources. Standard laboratory tests of total coliform are time-consuming and logistically inefficient for field data generation. Better and portable sensing technologies are needed. This paper reports an electrical impedance spectroscopic technique incorporated in a micro-fluidic chip with interdigitated microelectrodes to monitor the growth of microbial cells. Lag, log, and stationary phases of Escherichia coli cell growth with an integrated electrode are successfully detected, for samples of reverse osmosis water, standard treated tap water, and recycled water respectively. The results indicate that reverse osmosis water has a higher probability of contamination with bacterial pathogens compared to the other two types of water samples when subjected to the same amount of added nutrients. The statistical analysis shows a possible single detection range with higher-order regression, and repeat use of a single chip with the electrode was found to be within an acceptable limit. The interdigitated electrodes exposed to in-situ cell growth conditions and repeated electrical measurements have shown a promise for possible periodic or continuous monitoring. The paper further identifies several complimentary analysis methodologies that are robust towards phase noise in the measured impedance and are suited particularly for early-stage detection of bacterial contamination. The cell adhesion tendencies over the microelectrode due to the electric field need to be further analyzed.


Subject(s)
Biosensing Techniques , Microfluidics , Dielectric Spectroscopy , Electric Impedance , Electrochemical Techniques , Escherichia coli , Microelectrodes
5.
Physica A ; 574: 126014, 2021 Jul 15.
Article in English | MEDLINE | ID: mdl-33875903

ABSTRACT

Recent analysis of early COVID-19 data from China showed that the number of confirmed cases followed a subexponential power-law increase, with a growth exponent of around 2.2 (Maier and Brockmann, 2020). The power-law behavior was attributed to a combination of effective containment and mitigation measures employed as well as behavioral changes by the population. In this work, we report a random walk Monte Carlo simulation study of proximity-based infection spread. Control interventions such as lockdown measures and mobility restrictions are incorporated in the simulations through a single parameter, the size of each step in the random walk process. The step size l is taken to be a multiple of 〈 r 〉 , which is the average separation between individuals. Three temporal growth regimes (quadratic, intermediate power-law and exponential) are shown to emerge naturally from our simulations. For l = 〈 r 〉 , we get intermediate power-law growth exponents that are in general agreement with available data from China. On the other hand, we obtain a quadratic growth for smaller step sizes l ≲ 〈 r 〉 ∕ 2 , while for large l the growth is found to be exponential. We further performed a comparative case study of early fatality data (under varying levels of lockdown conditions) from three other countries, India, Brazil and South Africa. We show that reasonable agreement with these data can be obtained by incorporating small-world-like connections in our simulations.

6.
Biomicrofluidics ; 14(6): 064102, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33163137

ABSTRACT

Nano-material integrated microfluidic platforms are increasingly being considered to accelerate biological sample preparation and molecular diagnostics. A major challenge in this context is the generation of high electric fields for electroporation of cell membranes. In this paper, we have studied a novel mechanism of generating a high electric field in the microfluidic channels by using an array of semiconductor nanowires. When an electrostatic field is applied across a semiconductor nanowire array, the electric field is localized near the nanowires and the field strength is higher than what was reported previously with various other micro-geometries. Nanowires made of ZnO, Si, and Si-SiO2 and their orientation and array spacing are considered design parameters. It is observed that for a given ratio of the spacing between nanowires to the diameter, the electric field enhancement near the edges of ZnO nanowires is nearly 30 times higher compared to Si or Si-SiO2 nanowire arrays. This enhancement is a combined effect of the unique geometry with a pointed tip with a hexagonal cross section, the piezoelectric and the spontaneous polarization in the ZnO nanowires, and the electro-kinetics of the interface fluid. Considering the field localization phenomena, the trajectories of E. coli cells in the channel are analyzed. For a given inter-nanowire spacing and an applied electric field, the channels with ZnO nanowire arrays have a greater probability of cell lysis in comparison to Si-based nanowire arrays. Detailed correlations between the cell lysis probability with the inter-nanowire spacing and the applied electric field are reported.

7.
Biotechnol Lett ; 42(5): 853-863, 2020 May.
Article in English | MEDLINE | ID: mdl-32040672

ABSTRACT

OBJECTIVE: This study aims to detect pathogenic Escherichia coli (E. coli) bacteria using non-destructive fluorescence microscopy and micro-Raman spectroscopy. RESULTS: Raman vibrational spectroscopy provides additional information regarding biochemical changes at the cellular level. We have used two nanomaterials zinc oxide nanoparticles (ZnO-NPs) and gold nanoparticles (Au-NPs) to detect pathogenic E. coli. The scanning electron microscope (SEM) with energy dispersive X-ray (EDAX) spectroscopy exhibit surface morphology and the elemental composition of the synthesized NPs. The metal NPs are useful contrast agents due to the surface plasmon resonance (SPR) to detect the signal intensity and hence the bacterial cells. The changes due to the interaction between cells and NPs are further correlated to the change in the surface charge and stiffness of the cell surface with the help of the fluorescence microscopic assay. CONCLUSIONS: We conclude that when two E. coli strains (MTCC723 and MTCC443) and NPs are respectively mixed and kept overnight, the growth of bacteria are inhibited by ZnO-NPs due to changes in cell membrane permeability and intracellular metabolic system under fluorescence microscopy. However, SPR possessed Au-NPs result in enhanced fluorescence of both pathogens. In addition, with the help of Raman microscopy and element analysis, significant changes are observed when Au-NPs are added with the two strains as compared to ZnO-NPs due to protein, lipid and DNA/RNA induced conformational changes.


Subject(s)
Anti-Bacterial Agents/pharmacology , Escherichia coli/isolation & purification , Gold/pharmacology , Zinc Oxide/pharmacology , Anti-Bacterial Agents/chemistry , Cell Membrane Permeability , Escherichia coli/drug effects , Escherichia coli/pathogenicity , Escherichia coli Proteins/drug effects , Escherichia coli Proteins/metabolism , Gold/chemistry , Metal Nanoparticles/chemistry , Microbial Sensitivity Tests , Microscopy, Fluorescence , Surface Properties , Zinc Oxide/chemistry
8.
J Assoc Physicians India ; 67(11): 60-65, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31793271

ABSTRACT

Oral anticoagulants are commonly prescribed in patients with kidney diseases having atrial fibrillation and thromboembolic risk. It is very important to understand their clinical pharmacology and changes that may occur as GFR declines. Risks and benefits of newer oral anticoagulants are different in patients with CKD and patients with ESRD. Patients with GFR < 30 ml/min per 1.73 m2, including those on dialysis, were systematically excluded from landmark trials. All of the NOACs are dependent on renal clearance to some degree and so the risk of NOAC associated bleeding may be expected to be greater in patients with renal failure. Apixaban may be at least as safe as (or possibly safer than) warfarin in individuals with ESRD. Until more data become available, use of dabigatran, rivaroxaban, and edoxaban in patients with CKD stage 5 and ESRD is not indicated. Available strategies for reversing the anticoagulant effect of NOAC are - specific reversal agents available for dabigatran (idarucizumab) and for the oral direct factor Xa inhibitors - andexanet alfa, antifibrinolytic agents, DDAVP and prothrombin complex concentrates (PCCs). In this review clinical and pharmacological aspects of newer oral anticoagulants in the setting of chronic kidney disease will be discussed.


Subject(s)
Anticoagulants , Atrial Fibrillation , Renal Insufficiency, Chronic , Administration, Oral , Anticoagulants/pharmacology , Anticoagulants/therapeutic use , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Dabigatran/pharmacology , Dabigatran/therapeutic use , Factor Xa Inhibitors , Humans , Renal Insufficiency, Chronic/complications , Rivaroxaban/pharmacology , Rivaroxaban/therapeutic use
9.
Ultrasonics ; 93: 81-92, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30476786

ABSTRACT

In this paper, a thermodynamically consistent generalized three-dimensional modeling scheme is developed to simulate vibro-thermography and subsequently perform a quantitative investigation on a test structure. Simulation results are analyzed considering a plate with Structural Features (SF) which are used in a gas turbine engine structural components to reduce structural mass and enhance cooling. The modeling framework includes (i) coupled thermo-elastic heat generation and (ii) effects of various sources of nonlinear vibration arising due to the amplitude of the excitation, the engagement force on the target structure due to the ultrasonic horn, and structural boundary conditions. Transient heat generation behavior in the target structure with SF is analyzed. Dynamic contact models are used to capture the nonlinear harmonics. The effects of engagement force on the dynamic response are analyzed. Simulation results are obtained by incorporating the model in a finite element scheme. The simulation results show that the thermographic inspection can be optimally designed using a relationship between the SF sizes with reference to wavelength based resonance phenomenon. The spectral components obtained at various locations in the SF reveals the presence of both sub- and super-harmonics.

10.
ACS Appl Mater Interfaces ; 10(15): 12441-12452, 2018 Apr 18.
Article in English | MEDLINE | ID: mdl-29589895

ABSTRACT

Developing a biodegradable scaffold remains a major challenge in bone tissue engineering. This study was aimed at developing novel alginate-chitosan-collagen (SA-CS-Col)-based composite scaffolds consisting of graphene oxide (GO) to enrich porous structures, elicited by the freeze-drying technique. To characterize porosity, water absorption, and compressive modulus, GO scaffolds (SA-CS-Col-GO) were prepared with and without Ca2+-mediated crosslinking (chemical crosslinking) and analyzed using Raman, Fourier transform infrared (FTIR), X-ray diffraction (XRD), and scanning electron microscopy techniques. The incorporation of GO into the SA-CS-Col matrix increased both crosslinking density as indicated by the reduction of crystalline peaks in the XRD patterns and polyelectrolyte ion complex as confirmed by FTIR. GO scaffolds showed increased mechanical properties which were further increased for chemically crosslinked scaffolds. All scaffolds exhibited interconnected pores of 10-250 µm range. By increasing the crosslinking density with Ca2+, a decrease in the porosity/swelling ratio was observed. Moreover, the SA-CS-Col-GO scaffold with or without chemical crosslinking was more stable as compared to SA-CS or SA-CS-Col scaffolds when placed in aqueous solution. To perform in vitro biochemical studies, mouse osteoblast cells were grown on various scaffolds and evaluated for cell proliferation by using MTT assay and mineralization and differentiation by alizarin red S staining. These measurements showed a significant increase for cells attached to the SA-CS-Col-GO scaffold compared to SA-CS or SA-CS-Col composites. However, chemical crosslinking of SA-CS-Col-GO showed no effect on the osteogenic ability of osteoblasts. These studies indicate the potential use of GO to prepare free SA-CS-Col scaffolds with preserved porous structure with elongated Col fibrils and that these composites, which are biocompatible and stable in a biological medium, could be used for application in engineering bone tissues.


Subject(s)
Graphite/chemistry , Alginic Acid , Animals , Biocompatible Materials , Cell Proliferation , Chitosan , Collagen , Mice , Porosity , Tissue Engineering , Tissue Scaffolds
11.
Indian J Nephrol ; 26(5): 368-369, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27795633

ABSTRACT

Renal infarction usually occurs against a background of heart disease or a thromboembolic tendency and rarely is associated with infections. Here we present a case of a young boy who reported with painless gross hematuria following primary Varicella infection and was found to have an isolated renal infarct.

12.
Mater Sci Eng C Mater Biol Appl ; 63: 78-87, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27040198

ABSTRACT

Targeting of superior osteogenic drugs to bone is an ideal approach for treatment of osteoporosis. Here, we investigated the potential of using risedronate/zinc-hydroxyapatite (ZnHA) nanoparticles based formulation in a rat model of experimental osteoporosis. Risedronate, a targeting moiety that has a strong affinity for bone, was loaded to ZnHA nanoparticles by adsorption method. Prepared risedronate/ZnHA drug formulation was characterized by field-emission scanning electron microscopy, X-ray diffraction analysis and fourier transform infrared spectroscopy. In vivo performance of the prepared risedronate/ZnHA nanoparticles was tested in an experimental model of postmenopausal osteoporosis. Therapy with risedronate/ZnHA drug formulation prevented increase in serum levels of bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b better than risedronate/HA or risedronate. With respect to improvement in the mechanical strength of the femoral mid-shaft and correction of increase in urine calcium and creatinine levels, the therapy with risedronate/ZnHA drug formulation was more effective than risedronate/HA or risedronate therapy. Moreover, risedronate/ZnHA drug therapy preserved the cortical and trabecular bone microarchitecture better than risedronate/HA or risedronate therapy. Furthermore, risedronate/ZnHA drug formulation showed higher values of calcium/phosphorous ratio and zinc content. The results strongly implicate that risedronate/ZnHA drug formulation has a therapeutic advantage over risedronate or risedronate/HA therapy for the treatment of osteoporosis.


Subject(s)
Bone Density Conservation Agents/chemistry , Durapatite/chemistry , Nanoparticles/chemistry , Risedronic Acid/chemistry , Alkaline Phosphatase/metabolism , Animals , Bone Density Conservation Agents/therapeutic use , Bone and Bones/diagnostic imaging , Calcium/urine , Creatinine/urine , Disease Models, Animal , Drug Carriers/chemistry , Nanomedicine , Osteoporosis/drug therapy , Rats , Rats, Wistar , Risedronic Acid/therapeutic use , Tartrate-Resistant Acid Phosphatase/blood , X-Ray Diffraction , X-Ray Microtomography , Zinc/chemistry
13.
Rev. bras. reumatol ; 55(3): 240-250, May-Jun/2015. tab, graf
Article in Portuguese | LILACS | ID: lil-752092

ABSTRACT

Objetivos: O desuso pelo repouso no leito, pela imobilização de membros ou por missões espaciais provoca a perda óssea rápida. Fez-se este estudo para investigar os efeitos terapêuticos do ácido zoledrônico (ZOL), isoladamente e em combinação ao alfacalcidol (ALF), em um modelo de rato com osteoporose por desuso. Métodos: Ratos Wistar machos de três meses foram submetidos à imobilização da pata traseira direita (IPTD) por 10 semanas para induzir a osteopenia; em seguida, foram divididos em quatro grupos: 1 – IPTD para controle positivo; 2 – IPTD mais ZOL (50 µg/kg, dose única intravenosa); 3 – IPTD mais ALF (0,5 µg/kg, via oral diariamente); 4 – IPTD mais ALF (0,5 µg/kg, via oral diariamente) mais ZOL (50 µg/kg, dose única intravenosa) por outras 10 semanas. Um grupo de ratos não imobilizados foi usado como controle negativo. No fim do tratamento, os fêmures foram removidos e testaram-se a porosidade do osso e suas propriedades mecânicas, além do peso seco e das cinzas do osso. Resultados: A terapia combinada com ZOL mais ALF foi mais eficaz em reduzir a porosidade do osso do que a monoterapia com um dos fármacos administrado isoladamente em ratos submetidos à IPTD. No que diz respeito à melhoria da resistência mecânica da diáfise femoral média, o tratamento combinado com ZOL mais ALF foi mais eficaz do que a monoterapia com um dos fármacos administrado isoladamente. Além disso, a terapia combinada com ZOL mais ALF foi mais eficaz na melhoria do peso seco e das cinzas do osso do que a monoterapia com ZOL ou ALF em ratos submetidos à IPTD. Conclusões: Esses dados sugerem que a terapia combinada com ZOL mais ALF representa uma opção terapêutica potencialmente útil para o tratamento da osteoporose por desuso. .


Objectives: Disuse by bed rest, limb immobilization or space flight causes rapid bone loss. We conducted the present study to investigate the therapeutic effects of zoledronic acid (ZOL), alone and in combination with alfacalcidol (ALF) in a rat model of disuse osteoporosis. Methods: In the present study, 3-month-old male Wistar rats had their right hind-limb immobilized (RHLI) for 10 weeks to induce osteopenia, then were divided into four groups: 1 – RHLI positive control; 2 – RHLI plus ZOL (50 µg/kg, i.v. single dose); 3 – RHLI plus ALF (0.5 µg/kg, oral gauge daily); 4 – RHLI plus ALF (0.5 µg/kg, oral gauge daily) plus ZOL (50 µg/kg, i.v. single dose) for another 10 weeks. One group of non-immobilized rats was used as negative control. At the end of the treatment, the femurs were removed and tested for bone porosity, bone mechanical properties, and bone dry and ash weight. Results: Combination therapy with ZOL plus ALF was more effective in decreasing bone porosity than each drug administered as monotherapy in RHLI rats. With respect to improvement in the mechanical strength of the femoral mid-shaft, the combination treatment of ZOL plus ALF was more effective than each drug administered as a monotherapy. Moreover, combination therapy using ZOL plus ALF was more effective in improving dry bone and ash weight, than single-drug therapy using ZOL or ALF in RHLI rats. Conclusions: These data suggest that combination therapy with ZOL plus ALF represents a potentially useful therapeutic option for the treatment of disuse osteoporosis. .


Subject(s)
Rats , Bone Density Conservation Agents/therapeutic use , Diphosphonates/therapeutic use , Hydroxycholecalciferols/therapeutic use , Imidazoles/therapeutic use , Osteoporosis/drug therapy , Bone Density Conservation Agents/pharmacology , Diphosphonates/pharmacology , Disease Models, Animal , Drug Synergism , Hindlimb Suspension , Hydroxycholecalciferols/pharmacology , Imidazoles/pharmacology , Osteoporosis/etiology
14.
Rev. bras. reumatol ; 55(2): 103-112, Mar-Apr/2015. tab, graf
Article in Portuguese | LILACS | ID: lil-746141

ABSTRACT

Objetivos: Este estudo foi desenvolvido para investigar a eficácia e a segurança do ácidozoledrônico (ZOL) e do propranolol (PRO) como monoterapia e terapia combinada em ummodelo de rato com osteoporose pós-menopáusica. Métodos: Ratas Wistar fêmeas foram ovariectomizadas (OVX) ou submetidas à cirurgia simulada (placebo) aos três meses de idade. Doze semanas depois da cirurgia, as ratas foram divididas em seis grupos: (1) placebo + veículo; (2) OVX + veículo; (3) OVX + ZOL (100 µg/kg, dose única intravenosa); (4) OVX + ZOL (50 µg/kg, dose única intravenosa); (5) OVX + PRO (0,1 mg/kg, via subcutânea, cinco dias por semana); (6) OVX + ZOL (50 µg/kg, dose única intravenosa) + PRO (0,1 mg/kg, via subcutânea, cinco dias por semana) durante 12 semanas. Depois do tratamento, testou-se a densidade óssea, a porosidade e a microarquitetura tra-becular dos fêmures. Também foram avaliados marcadores bioquímicos séricos e urinários. Resultados: A terapia combinada com ZOL mais PRO foi mais eficaz em corrigir a diminuição do cálcio sérico e o aumento do nível sérico de fosfatase alcalina e fosfatase ácida resistenteao tartarato do que a monoterapia com ZOL ou PRO. Além disso, a terapia combinada comZOL mais PRO foi mais eficaz em corrigir o aumento dos níveis urinários de cálcio, fósforo ecreatinina do que a monoterapia com ZOL ou PRO. A terapia combinada com ZOL mais PRO também preservou a microarquitetura trabecular e a porosidade do osso cortical. Conclusão: Os resultados sugerem que a terapia combinada com ZOL mais PRO pode ser aabordagem mais eficaz para o tratamento da osteoporose grave em humanos. .


Objectives: The present study was designed to investigate further the efficacy and safety of zoledronic acid (ZOL) and propranolol (PRO) as monotherapy and combination therapy in a rat model of postmenopausal osteoporosis. Methods: Female Wistar rats were ovariectomized (OVX) or sham-operated at 3 months ofage. Twelve weeks post-surgery, rats were randomized into six groups: (1) sham + vehicle; (2) OVX + vehicle; (3) OVX + ZOL (100 뀅g/kg, i.v. single dose); (4) OVX + ZOL (50 뀅g/kg, i.v. single dose); (5) OVX + PRO (0.1 mg/kg, s.c. 5 days per week); (6) OVX + ZOL (50 뀅g/kg, i.v. single dose) + PRO (0.1 mg/kg, s.c. 5 days per week) for 12 weeks. After treatment, femurs were tested for bone density, porosity and trabecular micro-architecture. Biochemical markers in serum and urine were also determined. Results: Combined treatment with ZOL plus PRO corrected the decrease in serum calcium and increase in serum alkaline phosphatase and tartarate resistant acid phosphatase level better than single-drug therapy using ZOL or PRO. Moreover, combined treatment with ZOL plus PRO corrected the increase in urine calcium, phosphorous and creatinine level better than single-drug therapy using ZOL or PRO. Combination therapy using ZOL plus PRO also preserved the trabecular micro-architecture and cortical bone porosity. Conclusion: These data suggest that combined treatment with ZOL plus PRO could be a more effective approach for treating severe osteoporosis in humans. .


Subject(s)
Humans , Animals , Female , Rats , Adrenergic beta-Antagonists/pharmacology , Adrenergic beta-Antagonists/therapeutic use , Bone Density Conservation Agents/pharmacology , Bone Density Conservation Agents/therapeutic use , Bone Density/drug effects , Bone Diseases, Metabolic/drug therapy , Bone Remodeling/drug effects , Diphosphonates/pharmacology , Diphosphonates/therapeutic use , Imidazoles/pharmacology , Imidazoles/therapeutic use , Osteoporosis, Postmenopausal/drug therapy , Propranolol/pharmacology , Propranolol/therapeutic use , Biomarkers , Drug Synergism , Drug Therapy, Combination , Ovariectomy , Random Allocation
15.
Rev Bras Reumatol ; 55(2): 103-12, 2015.
Article in English | MEDLINE | ID: mdl-25582996

ABSTRACT

OBJECTIVES: The present study was designed to investigate further the efficacy and safety of zoledronic acid (ZOL) and propranolol (PRO) as monotherapy and combination therapy in a rat model of postmenopausal osteoporosis. METHODS: Female Wistar rats were ovariectomized (OVX) or sham-operated at 3 months of age. Twelve weeks post-surgery, rats were randomized into six groups: (1) sham + vehicle; (2) OVX + vehicle; (3) OVX + ZOL (100 µg/kg, i.v. single dose); (4) OVX + ZOL (50 µg/kg, i.v. single dose); (5) OVX + PRO (0.1 mg/kg, s.c. 5 days per week); (6) OVX + ZOL (50 µg/kg, i.v. single dose) + PRO (0.1 mg/kg, s.c. 5 days per week) for 12 weeks. After treatment, femurs were tested for bone density, porosity and trabecular micro-architecture. Biochemical markers in serum and urine were also determined. RESULTS: Combined treatment with ZOL plus PRO corrected decrease in serum calcium and increase in serum alkaline phosphatase and tartarate resistant acid phosphatase level better than single-drug therapy using ZOL or PRO. Moreover, combined treatment with ZOL plus PRO corrected increase in urine calcium, phosphorous and creatinine level better than single-drug therapy using ZOL or PRO. Combination therapy using ZOL plus PRO also preserved the trabecular micro-architecture and cortical bone porosity. CONCLUSION: These data suggest that combined treatment with ZOL plus PRO could be more effective approach for treating severe osteoporosis in humans.


Subject(s)
Adrenergic beta-Antagonists/pharmacology , Adrenergic beta-Antagonists/therapeutic use , Bone Density Conservation Agents/pharmacology , Bone Density Conservation Agents/therapeutic use , Bone Density/drug effects , Bone Diseases, Metabolic/drug therapy , Bone Remodeling/drug effects , Diphosphonates/pharmacology , Diphosphonates/therapeutic use , Imidazoles/pharmacology , Imidazoles/therapeutic use , Osteoporosis, Postmenopausal/drug therapy , Propranolol/pharmacology , Propranolol/therapeutic use , Animals , Biomarkers , Drug Synergism , Drug Therapy, Combination , Female , Humans , Ovariectomy , Random Allocation , Rats , Rats, Wistar , Zoledronic Acid
16.
Rev Bras Reumatol ; 55(3): 240-50, 2015.
Article in Portuguese | MEDLINE | ID: mdl-25440697

ABSTRACT

OBJECTIVES: Disuse by bed rest, limb immobilization or space flight causes rapid bone loss. We conducted the present study to investigate the therapeutic effects of zoledronic acid (ZOL), alone and in combination with alfacalcidol (ALF) in a rat model of disuse osteoporosis. METHODS: In the present study, 3-month-old male Wistar rats had their right hind-limb immobilized (RHLI) for 10 weeks to induce osteopenia, then were divided into four groups: 1- RHLI positive control; 2- RHLI plus ZOL (50 µg/kg, i.v. single dose); 3- RHLI plus ALF (0.5 µg/kg, oral gauge daily); 4- RHLI plus ALF (0.5 µg/kg, oral gauge daily) plus ZOL (50 µg/kg, i.v. single dose) for another 10 weeks. One group of non-immobilized rats was used as negative control. At the end of the treatment, the femurs were removed and tested for bone porosity, bone mechanical properties, and bone dry and ash weight. RESULTS: Combination therapy with ZOL plus ALF was more effective in decreasing bone porosity than each drug administered as monotherapy in RHLI rats. With respect to improvement in the mechanical strength of the femoral mid-shaft, the combination treatment of ZOL plus ALF was more effective than each drug administered as a monotherapy. Moreover, combination therapy using ZOL plus ALF was more effective in improving dry bone and ash weight, than single-drug therapy using ZOL or ALF in RHLI rats. CONCLUSIONS: These data suggest that combination therapy with ZOL plus ALF represents a potentially useful therapeutic option for the treatment of disuse osteoporosis.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Diphosphonates/therapeutic use , Hydroxycholecalciferols/therapeutic use , Imidazoles/therapeutic use , Osteoporosis/drug therapy , Animals , Bone Density Conservation Agents/pharmacology , Diphosphonates/pharmacology , Disease Models, Animal , Drug Synergism , Hindlimb Suspension , Hydroxycholecalciferols/pharmacology , Imidazoles/pharmacology , Male , Osteoporosis/etiology , Rats , Rats, Wistar , Zoledronic Acid
17.
Am J Otolaryngol ; 36(2): 122-9, 2015.
Article in English | MEDLINE | ID: mdl-25447932

ABSTRACT

OBJECTIVE: The aim of this study is to validate the applicability of the PolyVinyliDene Fluoride (PVDF) nasal sensor to assess the nasal airflow, in healthy subjects and patients with nasal obstruction and to correlate the results with the score of Visual Analogue Scale (VAS). METHODS: PVDF nasal sensor and VAS measurements were carried out in 50 subjects (25-healthy subjects and 25 patients). The VAS score of nasal obstruction and peak-to-peak amplitude (Vp-p) of nasal cycle measured by PVDF nasal sensors were analyzed for right nostril (RN) and left nostril (LN) in both the groups. Spearman's rho correlation was calculated. The relationship between PVDF nasal sensor measurements and severity of nasal obstruction (VAS score) were assessed by ANOVA. RESULTS: In healthy group, the measurement of nasal airflow by PVDF nasal sensor for RN and LN were found to be 51.14±5.87% and 48.85±5.87%, respectively. In patient group, PVDF nasal sensor indicated lesser nasal airflow in the blocked nostrils (RN: 23.33±10.54% and LN: 32.24±11.54%). Moderate correlation was observed in healthy group (r=-0.710, p<0.001 for RN and r=-0.651, p<0.001 for LN), and moderate to strong correlation in patient group (r=-0.751, p<0.01 for RN and r=-0.885, p<0.0001 for LN). CONCLUSION: PVDF nasal sensor method is a newly developed technique for measuring the nasal airflow. Moderate to strong correlation was observed between PVDF nasal sensor data and VAS scores for nasal obstruction. In our present study, PVDF nasal sensor technique successfully differentiated between healthy subjects and patients with nasal obstruction. Additionally, it can also assess severity of nasal obstruction in comparison with VAS. Thus, we propose that the PVDF nasal sensor technique could be used as a new diagnostic method to evaluate nasal obstruction in routine clinical practice.


Subject(s)
Diagnostic Techniques, Respiratory System/instrumentation , Nasal Obstruction/diagnosis , Polyvinyls , Rhinomanometry/instrumentation , Rhinomanometry/methods , Adult , Analysis of Variance , Case-Control Studies , Equipment Design , Female , Humans , Male , Middle Aged , Nasal Cavity/physiopathology , Nasal Obstruction/physiopathology , Reference Values , Transducers , Visual Analog Scale
18.
Sci Pharm ; 82(2): 357-74, 2014.
Article in English | MEDLINE | ID: mdl-24959400

ABSTRACT

Disuse by bed rest, limb immobilization, or space flight causes rapid bone loss by arresting bone formation and accelerating bone resorption. Propranolol (a non-selective ß-adrenergic antagonist) has been shown to improve bone properties by increasing bone formation and decreasing bone resorption in an ovariectomy-induced rat model. However, no studies have yet compared the osteoprotective properties of propranolol with well-accepted therapeutic interventions for the treatment and prevention of immobilization/disuse osteoporosis. To clarify this, we investigated the effects of propranolol compared with zoledronic acid and alfacalcidol in a new animal model of immobilization/disuse osteoporosis. Three-month-old male Wistar rats were divided into five groups with six animals in each group: (1) immobilized (IMM) control; (2) normal control; (3) IMM + zoledronic acid (50 µg/kg, intravenous single dose); (4) IMM + alfacalcidol (0.5 µg/kg, per oral daily); (5) IMM + propranolol (0.1 mg/kg, subcutaneously 5 days/week) for 10 weeks. In groups 1 and 3-5, the right hindlimb was immobilized. At the end of treatment, the femurs were removed and tested for bone porosity, bone mechanical properties, and cortical microarchitecture. Treatment with propranolol induced greater reductions in the bone porosity of the right femur and improved the mechanical properties of the femoral mid-shaft femur in comparison to the IMM control. Moreover, treatment with propranolol also improved the microarchitecture of cortical bones when compared with the IMM control, as indicated by scanning electron microscopy. The anti-osteoporotic property of propranolol was comparable with zoledronic acid and alfacalcidol. This study shows that the bone resorption induced by immobilization/disuse in rats can be suppressed by treatment with propranolol.

19.
J Osteoporos ; 2014: 586431, 2014.
Article in English | MEDLINE | ID: mdl-24800099

ABSTRACT

We conducted the present study to investigate the therapeutic effects of propranolol (PRO), alone and in combination with the antiresorptive agent ZOL, in a rat model of postmenopausal osteoporosis. Female Wistar rats were OVX or sham-operated at 3 months of age. Twelve weeks after surgery, rats were randomized into six groups: (1) sham + vehicle, (2) OVX + vehicle, (3) OVX + ZOL (100 µ g/kg, i.v. single dose), (4) OVX + ZOL (50 µ g/kg, i.v. single dose), (5) OVX + PRO (0.1 mg/kg, s.c. 5 days per week), and (6) OVX + ZOL (50 µ g/kg, i.v. single dose) + PRO (0.1 mg/kg, s.c. 5 days per week) for 12 weeks. At the end of treatment study, various bone parameters were evaluated. With respect to improvement in the mechanical strength of the lumbar spine and the femoral mid-shaft, the combination treatment of ZOL and PRO was more effective than each drug administered as a monotherapy. Moreover, combination therapy using ZOL and PRO preserved the trabecular microarchitecture better than single-drug therapy using ZOL or PRO in OVX rats. These data suggest that combination therapy with ZOL plus PRO represents a potentially useful therapeutic option for patients with osteoporosis.

20.
Am J Rhinol Allergy ; 28(1): e62-7, 2014.
Article in English | MEDLINE | ID: mdl-24717887

ABSTRACT

BACKGROUND: Deviated nasal septum (DNS) is one of the major causes of nasal obstruction. Polyvinylidene fluoride (PVDF) nasal sensor is the new technique developed to assess the nasal obstruction caused by DNS. This study evaluates the PVDF nasal sensor measurements in comparison with PEAK nasal inspiratory flow (PNIF) measurements and visual analog scale (VAS) of nasal obstruction. METHODS: Because of piezoelectric property, two PVDF nasal sensors provide output voltage signals corresponding to the right and left nostril when they are subjected to nasal airflow. The peak-to-peak amplitude of the voltage signal corresponding to nasal airflow was analyzed to assess the nasal obstruction. PVDF nasal sensor and PNIF were performed on 30 healthy subjects and 30 DNS patients. Receiver operating characteristic was used to analyze the DNS of these two methods. RESULTS: Measurements of PVDF nasal sensor strongly correlated with findings of PNIF (r = 0.67; p < 0.01) in DNS patients. A significant difference (p < 0.001) was observed between PVDF nasal sensor measurements and PNIF measurements of the DNS and the control group. A cutoff between normal and pathological of 0.51 Vp-p for PVDF nasal sensor and 120 L/min for PNIF was calculated. No significant difference in terms of sensitivity of PVDF nasal sensor and PNIF (89.7% versus 82.6%) and specificity (80.5% versus 78.8%) was calculated. CONCLUSION: The result shows that PVDF measurements closely agree with PNIF findings. Developed PVDF nasal sensor is an objective method that is simple, inexpensive, fast, and portable for determining DNS in clinical practice.


Subject(s)
Diagnostic Techniques, Respiratory System/instrumentation , Nasal Obstruction/diagnosis , Nasal Septum/pathology , Polyvinyls , Adult , Aged , Female , Humans , Inhalation , Male , Middle Aged , ROC Curve , Sensitivity and Specificity , Young Adult
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