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1.
Sci Rep ; 9(1): 15316, 2019 10 25.
Article in English | MEDLINE | ID: mdl-31653893

ABSTRACT

Doxycycline, a member of the tetracycline family, is a drug used as an antibiotic (dosage of 100 mg/day) and as an anti-inflammatory drug on the dosage of 20 mg twice a day, this use has Matrix Metalloproteinases (MMP) inhibitor action. Doxycycline is a calcium chelator and therefore interferes in bone remodeling. The main objective of this study was to evaluate the action of the drug doxycycline in the control of osteopenia. Sixty three Wistars rats were divided into 9 groups with n = 7 each, as follow: the control group with doxycycline 10 mg/kg/day (C10), control with doxycycline 30 mg/kg/day (C30) and control (C), ovariectomized group with doxycycline 10 mg/kg/day (OVX10), ovariectomized with doxycycline 30 mg/kg/day (OVX30), and ovariectomized with water (OVX), sedentary group with 10 mg/kg/day (Se10), sedentary with doxycycline 30 mg/kg/day (Se30), and sedentary group with water (Se). Left femoral bone was used for bone densitometry, right femoral bone for histological analysis. The right tibia was intended for chemical quantifications, the total serum was used for cholesterol and calcium quantification. The length of the left femoral bone was measured after the densitometry analysis. Statistical analysis was performed using multivariate general linear model (ANOVA two factors with Bonferroni adjustment) and the TRAP analysis was subjected to normality test and then were subjected to nonparametric test, both with p < 0.05 significance. Statistically significant differences were found, with better results for the groups exposed to the medication (10 and 30 mg/kg/day): Se vs. Se10 and Se vs. Se30 for BMC, quantification of magnesium, amount of cancellous bone in the distal portion; OVX vs. OVX10 for BMC, BMD and calcium in serum; OVX vs. OVX10 and OVX30 for quantification in proximal and distal portion of cancellous bone; Se vs. Se30 and OVX vs. OVX30 for immunostaining for TRAP, all results with minimum of p ≤ 0.05. Doxycycline had a deleterious effect on control groups and positive action for bone organization on female rats affected by bilateral ovariectomy-induced osteopenia and sedentary lifestyle.


Subject(s)
Bone Diseases, Metabolic/drug therapy , Doxycycline/therapeutic use , Animals , Body Weight/drug effects , Bone Diseases, Metabolic/pathology , Calcium/analysis , Cancellous Bone/drug effects , Cancellous Bone/pathology , Doxycycline/chemistry , Doxycycline/pharmacology , Female , Femur/drug effects , Femur/pathology , Magnesium/analysis , Public Health , Rats, Wistar , Tartrate-Resistant Acid Phosphatase/metabolism , Zinc/analysis
2.
Curr Pharm Des ; 24(16): 1801-1810, 2018.
Article in English | MEDLINE | ID: mdl-29865998

ABSTRACT

Osteoporosis and cardiovascular diseases are common causes of morbidity and mortality worldwide, especially in people aged over 60 years. Osteoporosis is characterized by low bone mineral density, which deteriorates the microarchitecture of bones and increases the risk of bone fractures. Other pathologies also constitute risk factors for the development of osteoporosis, mainly cardiovascular diseases. In fact, a growing number of reports have shown a positive correlation between cardiovascular diseases and low bone mineral density. MMPs are proteases that participate in the organized degradation of the extracellular matrix (ECM) and which play essential physiological roles, such as cardiovascular and bone tissue remodeling. Overexpression of MMPs underlies pathological processes like osteoporosis and cardiovascular diseases. MMP-1, -2, -9, -13, and -14 are expressed in bone tissue and are key players in the digestion of bone matrix by osteoblasts. Considering this relationship between osteometabolic and cardiovascular pathologies and MMPs, this review focuses on the involvement of MMPs in osteoporosis and on their participation in cardiovascular diseases; it also deals with the positive correlation between osteoporosis and cardiovascular diseases. Although there are many drugs to treat osteoporosis, controversies exist. Here, we will describe these controversies and will discuss how inhibition of MMPs could be an alternative strategy to or an adjuvant therapy in the current treatment of osteoporosis.


Subject(s)
Cardiovascular Diseases/metabolism , Matrix Metalloproteinases/metabolism , Osteoporosis/metabolism , Animals , Cardiovascular Diseases/drug therapy , Humans , Osteoporosis/drug therapy , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology
3.
Biomed Mater ; 13(2): 025022, 2018 02 08.
Article in English | MEDLINE | ID: mdl-29053112

ABSTRACT

Bone grafts are used in the medical-surgical field for anatomical and functional reconstruction of lost bone areas, aiding the bone repair process by osteogenesis, osteinduction and osteoconduction. New materials such as F1 (fraction 1) protein extracted from the rubber tree Hevea brasiliensis have been investigated and currently present important properties for tissue repair, and are associated with neoangiogenesis, promoting cell adhesion and extracellular matrix formation. The main objective of this study was to investigate the association of F1 protein to different bone grafts in the repair of critical bone defects in the calvaria of Wistar rats. A total of 112 Wistar rats were divided as follows: autograft (AuG), allograft (AlG), xenograft (XeG), autograft/F1 (AuG-F1), allograft/F1 (AlG-F1), xenograft/F1 (XeG-F1), F1 (F1), control (CTL), with a waiting period of 4 and 6 weeks (w). The stereological AuG, AlG, AuG-F1 and AlG-F1 results had greater bone neoformation (p < 0.05). For immunohistochemistry, the angiogenic and osteogenic factors were higher for AuG-F1 and AlG-F1. TRAP-positive cells were higher in XeG-F1 and AlG (37 ± 9.53, 13.3 ± 4.16) (4 w) and XeG, AlG-F1 and XeG-F1 (20.33 ± 7.37; 15.25 ± 6.02, 19.33 ± 3.21) (6 w). For zymography, F1 showed increased gelatinolytic activity of MMP-2 and -9. It was concluded that the bone graft associated or not with F1 increases the angiogenic and osteogenic, biochemical and stereological factors.


Subject(s)
Bone Regeneration , Bone Transplantation/methods , Latex/therapeutic use , Animals , Cell Adhesion , Extracellular Matrix , Heterografts , Hevea , Immunohistochemistry , Latex/chemistry , Male , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Osteogenesis/drug effects , Peroxidases/chemistry , Rats , Rats, Wistar , Skull/drug effects , Transplantation, Autologous , Transplantation, Homologous , Vascular Endothelial Growth Factor A
4.
J Photochem Photobiol B ; 174: 126-132, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28772237

ABSTRACT

Acute arthritis is an inflammation that affects many joints. The principal treatment options comprise drugs (corticosteroids), invasive and painful surgery. The objective of this study was to evaluate the efficacy of low intensity laser therapy (LILT), a non-invasive treatment, in a murine model of acute inflammation model. 48 mice received a synovial injection of Zymosan A into one knee. Mice were treated with LILT by three different wavelengths, either as a single (S) or dual (D) application immediately after the injury or after 24h following initiation of an inflammatory response. The histological analysis aimed at identifying inflammatory infiltrate and the structure of the articular surfaces as an indicator of a long-term damage due to inflammation. Statistical analysis (Kruskal-Wallis test), did not allow to reject the null hypothesis. However, LILT promoted histological alterations in some treatment groups. Histological evidence (Median and confidence interval) of anti-inflammatory effects was especially noticeable in knees of mice irradiated with lasers emitting moderate intensity and continuous 660nm (S=18.5 (11.4; 27.6); D=16.0 (6.93; 27.0)) and high intensity and pulsed 905nm (S=17.5 (10.2; 24.79), with decrease of the resorbed region. However, the 905nm pulsed laser was responsible for exacerbation of inflammation for multiple LILT sessions with a short delay (D=45.0 (22.84; 63.83)), tending to aggravate the resorption of the articular surface (p<0.05). LILT showed signs of an anti-inflammatory effect when applied once, but promoted increased resorptive area when used for two sessions, indicating the importance of a controlled LILT protocol to reach therapeutic effects.


Subject(s)
Arthritis/radiotherapy , Low-Level Light Therapy , Acute Disease , Animals , Arthritis/chemically induced , Arthritis/metabolism , Arthritis/pathology , Lipopolysaccharides/pharmacology , Male , Mice , Osteocalcin/metabolism , Osteoprotegerin/metabolism , RANK Ligand/metabolism , Tartrate-Resistant Acid Phosphatase/metabolism
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