Effect of collagenase ointment on a radiofrequency induced abrasive wound

• Aim: Radiofrequency is one of the methods used to treat wrinkles and skin lesions, but its application may result in an abrasive wound. The purpose of this study was to evaluate the effect of collagenase ointment on the epithelial healing of an abrasive wound induced by a radiofrequency system. • Methods: An abrasive wound was produced using radiofrequency at the dorsal midline of 30 guinea pigs, which were randomly divided into 2 groups: one group were treated with saline solution and the other group treated with collagenase ointment; both used twice daily. The animals were sacrificed at 1, 7, 15, 30 and 60 postoperative days. Macroscopic, histological and morphometric evaluations were performed and the results were submitted to statistical analysis. • Results: The animals treated with collagenase ointment presented accelerated healing process and less inflammatory cell infiltration than the saline solution treated animals from one to fifteen postoperative days. Morphometric evaluation showed a thicker epidermis and a thinner dermis layer in the saline solution group at one and seven postoperative days, but significant differences between both groups were not observed at thirty and sixty postoperative days. • Conclusion: According to our results the use of collagenase ointment may accelerate the healing process of a radiofrequency induced abrasive wound.

Bone regeneration in cranioplasty and clinical complications in rabbits with alloxan-induced diabetes

This research evaluated the bone repair process in surgical defects created on the parietal bones of diabetic rabbits using the guided bone regeneration technique to observe the effects of alloxan in the induction of diabetes mellitus. Twenty-four adult rabbits were divided into three study groups: control (C), diabetic (D) and diabetic associated to polytetrafluoroethylene (PTFE) membrane (D-PTFE). For diabetes induction the animals received one dose of monohydrated alloxan (90 mg/kg) by intravenous administration in the auricular or femoral vein. In group D-PTFE the membrane covered both the floor and the surface of the bone defect. In groups D and C, the bone defect was filled up with blood clot. The specimens were fixed in 10% formol and prepared for histomorphometric analysis. The results showed that the 90 mg/kg dose of monohydrate alloxan was sufficient to promote diabetes mellitus when administered in the auricular vein. Bone regeneration was slower in the diabetic group when compared with the control and diabetic-PTFE groups, but there was no significant statistical difference between the two experimental groups (D and D-PTFE). The oral and general clinical complications among the diabetics were weight loss, polyuria, polyphagia and severe chronic gingivitis.

MTA-induced neutrophil recruitment: a mechanism dependent on IL-1β, MIP-2, and LTB4

Objective: The objective of this study was to investigate the mediators and the resident peritoneal cells involved in the neutrophil migration (NM) induced by mineral trioxide aggregate (MTA) in mice. Study design: MTA (25 mg/cavity) was injected into normal and pretreated peritoneal cavities (PC) with indomethacin (IND), dexamethasone (DEX), BWA4C, U75302, antimacrophage inflammatory protein-2 (MIP-2), and anti-interleukin-1β (IL-1β) antibodies and the NM was determined. The role of macrophage (MO) and mast cells (MAST) was determined by administration of thioglycollate 3% or 48/80 compound, respectively. The concentration of IL-1β and MIP-2 exudates was measured by ELISA. Results: MTA induced dose- and time-dependent NM into mice PC, with the participation of MO and MAST. NM was inhibited by DEX, BWA4C, and U75302, as well as anti-MIP-2 and anti-IL-1β antibodies. In the exudates, IL-1β and MIP-2 were detected. Conclusions: This study suggests that MTA induces NM via a mechanism dependent on MAST and MO mediated by IL-1β, MIP-2, and LTB4. © 2008 Mosby, Inc. All rights reserved.

The possible involvement of hyperpolarizing mechanisms in histamine-induced relaxation of the rat portal vein

The present study evaluated the effects of histamine 10 -2 M on longitudinal preparations of rat portal vein. It was observed that histamine 10 -2 M induced relaxation of rat portal vein preparations pre-contracted with phenylephrine 10 -4 M. On the other hand, no pharmacological effects were observed in preparations not pre-contracted. The observed histamine-induced relaxing effect was absent in preparations pre-contracted with KCl (120 mM) or in the presence of depolarizing nutritive solution. However, the histamine-induced relaxation was still present in the endothelium-removed preparations. The histamine-induced relaxation also was not prevented by astemizole (10 -6 M, 10 -5 M and 10 -4 M), cimetidine (10 -5 M, 10 -4 M and 10 -3 M) or thioperamide (10 -6 M, 10 -5 M and 10 -4 M), selective antagonists H 1, H 2 and H 3, respectively. The presence of L-NAME 10 -4 M or L-NAME 10 -4 M plus indomethacin 10 -5 M also did not prevent the histamine-induced relaxation observed in rat portal vein. Thus, the histamine-induced relaxation observed in rat portal vein appears to involve a non-endothelial hyperpolarizing mechanism independent of H 1, H 2 and H 3 receptors.

LH surge in Nelore cows (Bos indicus), after induced estrus or after ovarian superestimulation

Considering that there is limited information about the preovulatory LH surge in Zebu cattle (Bos indicus), the purpose of the present work was to assess the LH surge in Nelore cows during the estrous cycle and after ovarian superestimulation of ovarian follicular development with FSH. This information is particularly important to improve superovulatory protocols associated with fixed-time artificial insemination. Nelore cows (n = 12) had their estrus synchronized with an intravaginal device containing progesterone (CIDR-B ®) associated with estradiol benzoate administration (EB, 2.5 mg, i.m., Day 0). Eight days later all animals were treated with PGF2α (Day 8) in the morning (8:00 h) and at night, when CIDR devices were removed (20:00 h). Starting 38 h after the first PGF2α injection, blood sampling and ovarian ultrasonography took place every 4 h, during 37 consecutive hours. Frequent handling may have resulted in a stress-induced suppression of LH secretion resulting in only 3 of 12 cows having ovulations at 46.7 ± 4.9 and 72.3 ± 3.8 h, respectively, after removal of CIDR-B. Thirty days later, the same animals received the described hormonal treatment associated with FSH (Folltropin ®, total dose = 200 mg) administered twice a day, during 4 consecutive days, starting on Day 5. Thirty-six hours after the first injection of PGF2α, to minimize stress, only seven blood samples were collected at 4 h interval each, and ultrasonography was performed every 12 h until ovulation. In 11 of 12 cows (92%) the LH surge and ovulation were observed 34.6 ± 1.6 and 59.5 ± 1.9 h, respectively, after removal of progesterone source. The maximum values for LH in those animals were 19.0 ± 2.6 ng/ml (mean ± S.E.M.). It is concluded that, in Nelore cows submitted to a ovarian superstimulation protocol, the LH surge occurs approximately 35 h after removal of intravaginal device containing progesterone, and approximately 12 h before the LH surge observed after an induced estrus without ovarian superstimulation. © 2008 Elsevier B.V. All rights reserved.

Plasma lipid profile of experimentally induced hyperlipidemic New Zealand white rabbits is not affected by resveratrol

Hyperlipidemia is well recognized as an important risk factor in the development of atherosclerosis. Low-density lipoproteins (LDL) are components of cholesterol that are highly associated to an increased risk of cardiovascular diseases. Hypercholesterolemia induces proteolytic and oxidative changes in vasculature, leading to a local inflammatory response. Since dietary antioxidants have attracted considerable attention as preventive and therapeutic agents, the polyphenolic compound resveratrol seems to play an important role in prevention of human atherosclerosis. Researches show that resveratrol inhibits LDL oxidation and platelet aggregation, as well as vascular prolifer ation of smooth muscle cells. However, recent findings in animal models reveal conflicting results regarding its effects on plasma lipid levels. The aim of the present study was to evaluate the effect of resveratrol on plasma biochemistry profile in New Zealand white rabbits submitted to a hypercholesterolemic diet. Twenty healthy, male, adult New Zealand white rabbits were fed with ordinary diet for one week before being divided into four treatment groups, containing five animals each. Group CT received maintenance diet; group R received maintenance diet and resveratrol (3mg/kg/day) given orally; group CL received maintenance diet enriched with 1.5% cholesterol; and group CR received maintenance diet enriched with 1.5% cholesterol and resveratrol (3mg/kg/day) given orally. During the experiment, from each animal, samples of 3mL venous blood were collected in heparin twice monthly for measurements of total cholesterol, triglycerides, and low- and high-density lipoproteins. The data analysis revealed that resveratrol did not have a hypolipidemic effect in experimentally induced hypercholesterolemic New Zealand white rabbits.

Cardiovascular remodeling induced by passive smoking

Coronary heart disease (CHD) is the most common cause of death in many developed countries. The major risk factors for CHD are smoking, high blood pressure, diabetes, high cholesterol levels, and lack of physical activity. Importantly, passive smoke also increases the risk for CHD. The mechanisms involved in the effects of passive smoke in CHD are complex and include endothelial dysfunction, lipoprotein modification, increased inflammation and platelet activation. Recently, several studies have shown that exposure to tobacco smoke can result in cardiac remodeling and compromised cardiac function. Potential mechanisms for these alterations are neurohumoral activation, oxidative stress, and MAPK activation. Although the vascular effects of cigarette smoke exposure are well known, the effects of tobacco smoking on the heart have received less attention. Therefore, this review will focus on the recent findings as to the effects of passive smoking in acute and chronic phases of vascular and cardiac remodeling. © 2009 Bentham Science Publishers Ltd.

Evaluation of tissue reaction, cell viability and cytokine production induced by Sealapex Plus

The aim of this study was to investigate the effects of mineral trioxide aggregate (MTA), Sealapex, and a combination of Sealapex and MTA (Sealapex Plus) on the reaction of subcutaneous connective tissue of rats, and on cell viability and cytokine production in mouse fibroblasts. The tissue reaction was carried out with dentin tubes containing the materials implanted in the dorsal connective tissue of rats. The histological analysis was performed after 7 and 30 days. Millipore culture plate inserts with polyethylene tubes filled with materials were placed into 24-well cell culture plates with mouse fibroblasts to evaluate the cell viability by MTT assay. ELISA assays were also performed after 24 h of exposure of the mouse fibroblasts to set material disks. Histopathologic examination showed Von Kossa-positive granules that were birefringent to polarized light for all the studied materials at the tube openings. No material inhibited the cell viability in the in vitro test. It was detected IL-6 production in all root-end filling materials. MTA and Sealapex Plus induced a slight raise of mean levels of IL-1β. The results suggest that Sealapex Plus is biocompatible and stimulates the mineralization of the tissue.

Cimetidine-induced vascular cell apoptosis impairs testicular microvasculature in adult rats

Cimetidine, an H2 receptor antagonist used for treatment of gastric ulcers, exerts antiandrogenic and antiangiogenic effects. In the testes cimetidine impairs spermatogenesis, Sertoli cells and peritubular tissue, inducing apoptosis in the myoid cells. Regarding the importance of histamine and androgens for vascular maintenance, the effect of cimetidine on the structural integrity of the testicular vasculature was evaluated. Adult male rats received cimetidine (CMTG) and saline (CG) for 50 days. The testes were fixed in buffered 4% formaldehyde and embedded in historesin and paraffin. In the PAS-stained sections, the microvascular density (MVD) and the vascular luminal area (VLA) were obtained. TUNEL method was performed for detection of cell death. Testicular fragments embedded in Araldite were analyzed under transmission electron microscopy. A significant decrease in the MVD and VLA and a high number of collapsed blood vessel profiles were observed in CMTG. Endothelial cells and vascular muscle cells were TUNEL-positive and showed ultrastructural features of apoptosis. These results indicate that cimetidine induces apoptosis in vascular cells, leading to testicular vascular atrophy. A possible antagonist effect of cimetidine on the H2 receptors and/or androgen receptors in the vascular cells may be responsible for the impairment of the testicular microvasculature.

Advances in drug design based on the amino acid approach: Taurine analogues for the treatment of CNS diseases

Amino acids are well known to be an important class of compounds for the maintenance of body homeostasis and their deficit, even for the polar neuroactive aminoacids, can be controlled by supplementation. However, for the amino acid taurine (2-aminoethanesulfonic acid) this is not true. Due its special physicochemical properties, taurine is unable to cross the blood-brain barrier. In addition of injured taurine transport systems under pathological conditions, CNS supplementation of taurine is almost null. Taurine is a potent antioxidant and anti-inflammatory semi-essential amino acid extensively involved in neurological activities, acting as neurotrophic factor, binding to GABA A/glycine receptors and blocking the excitotoxicity glutamate-induced pathway leading to be a neuroprotective effect and neuromodulation. Taurine deficits have been implicated in several CNS diseases, such as Alzheimer's, Parkinson's, epilepsy and in the damage of retinal neurons. This review describes the CNS physiological functions of taurine and the development of new derivatives based on its structure useful in CNS disease treatment.&; 2012 by the authors; licensee MDPI, Basel, Switzerland.

Tachycardia-induced cardiomyopathy

Tachycardia-induced cardiomyopathy (TIC) is an important cause of heart failure as it is potentially reversible after ventricular rate control. A 66-year-old hypertensive woman presented with a 15-day history of tachycardia, dyspnoea and oedema. ECG revealed atrial fibrillation with ventricular frequency of 130 beats per minute (bpm). Echocardiogram showed dilated left ventricle (LV) with 0.39 ejection fraction. Angiography revealed non-obstructed coronary arteries. Heart rate and cardiac failure were controlled with amiodarone, digoxine, captopril, metoprolol and furosemide. During follow-up, despite drug dose optimisation, the patient kept complaining of tachycardia and dyspnoea with a ventricular rate between 108 and 120 bpm. Medical staff suspected she was not taking her medicines properly. Two months later, the patient was asymptomatic and had converted to sinus rhythm (heart rate of 76 bpm). Echocardiogram showed normal LV size and function. Patient 's diagnosis was TIC. Although rare, TIC should be considered in all cases of systolic dysfunction associated with tachyarrhythmia. Copyright 2012 BMJ Publishing Group. All rights reserved.

Cardiac remodeling induced by smoking: Concepts, relevance, and potential mechanisms

Cardiac or ventricular remodeling is characterized by molecular, cellular, and interstitial alterations that lead to changes in heart size, mass, geometry and function in response to a given insult. Currently, tobacco smoke exposure is recognized as one of these insults. Indeed, tobacco smoke exposure induces the enlargement of the left-sided cardiac chambers, myocardial hypertrophy, and ventricular dysfunction. Potential mechanisms for these alterations include hemodynamic and neurohormonal changes, oxidative stress, inflammation, nitric oxide bioavailability, matrix metalloproteinases and mitogen-activated protein kinase activation. This review will focus on the concepts, relevance, and potential mechanisms of cardiac remodeling induced by tobacco smoke. © 2012 Bentham Science Publishers.

Urea-induced unfolding of Glossoscolex paulistus hemoglobin, in oxy- and cyanomet-forms: A dissociation model

The urea effect on the giant extracellular hemoglobin of Glossoscolex paulistus (HbGp) stability was studied by analytical ultracentrifugation (AUC) and small angle X-ray scattering (SAXS). AUC data show that the sedimentation coefficient distributions curves c (S), at 1.0mol/L of urea, display a single peak at 57 S, associated to the undissociated protein. The increase in urea concentration, up to 4.0mol/L, induces the appearance of smaller species, due to oligomeric dissociation. The sedimentation coefficients and molecular masses are 9.2S and 204kDa for the dodecamer (abcd)3, 5.5S and 69kDa for the tetramer (abcd), 4.1S and 52kDa for the trimer (abc) and 2.0 S and 17kDa for the monomer d, respectively. SAXS data show initially a decrease in the I(0) values due to the oligomeric dissociation, and then, above 4.0mol/L of denaturant, for oxy-HbGp, and above 6.0mol/L for cyanomet-HbGp, an increase in the maximum dimension and gyration radius is observed, due to the unfolding process. According to AUC and SAXS data the HbGp unfolding is described by two phases: the first one, at low urea concentration, below 4.0mol/L, characterizes the oligomeric dissociation, while the second one, at higher urea concentration, is associated to the unfolding of dissociated species. Our results are complementary to a recent report based on spectroscopic observations. © 2012 Elsevier B.V.

Photodynamic therapy for the treatment of induced mammary tumor in rats

The objective of this work was to evaluate photodynamic therapy (PDT) by using a hematoporphyrin derivative as a photosensitizer and light-emitting diodes (LEDs) as light source in induced mammary tumors of Sprague-Dawley (SD) rats. Twenty SD rats with mammary tumors induced by DMBA were used. Animals were divided into four groups: control (G1), PDT only (G2), surgical removal of tumor (G3), and submitted to PDT immediately after surgical removal of tumor (G4). Tumors were measured over 6 weeks. Lesions and surgical were LEDs lighted up (200 J/cm2 dose). The light distribution in vivo study used two additional animals without mammary tumors. In the control group, the average growth of tumor diameter was approximately 0.40 cm/week. While for PDT group, a growth of less than 0.15 cm/week was observed, suggesting significant delay in tumor growth. Therefore, only partial irradiation of the tumors occurred with a reduction in development, but without elimination. Animals in G4 had no tumor recurrence during the 12 weeks, after chemical induction, when compared with G3 animals that showed 60 % recurrence rate after 12 weeks of chemical induction. PDT used in the experimental model of mammary tumor as a single therapy was effective in reducing tumor development, so the surgery associated with PDT is a safe and efficient destruction of residual tumor, preventing recurrence of the tumor. © 2012 Springer-Verlag London Ltd.

Doxorubicin induced dilated cardiomyopathy in a rabbit model: An update

Dilated cardiomyopathy (DCM) is characterized by chamber dilation and cardiac dysfunction. Because of the poor prognosis, models are needed for the investigation of and development of new therapeutic approaches, as well as stem cell therapy. Doxorubicin (DOX), used as chemotherapeutic agent, is reported to be cumulative cardiotoxic causing DCM. The aim of the study was to investigate the onset of systolic dysfunction using echocardiography in rabbits receiving two different doses of DOX (1. mg/kg twice a week and 2. mg/kg once a week). Twenty rabbits were treated with doxorubicin in two different doses for 6. weeks and compared with a control group treated with NaCl 0.9%. The effect of doxorubicin on the myocardium was investigated with histological analysis and scanning electron microscopy of left ventricle (LV), as well as in the interventricular septum (IVS) and right ventricle (RV). The results showed a high mortality rate for rabbits receiving 2. mg/kg once a week. A significant reduction in systolic function was present in animals treated with DOX after 6. weeks, with decreased ejection fraction and shortening fraction. Histology and electron microscopy revealed vacuolization, intracytoplasmic granulation, necrosis and interstitial fibrosis in LV, as well as in the IVS and RV. Doxorubicin induced changes are present in the LV, RV and IVS, and the administration at the dose of 1. mg/kg twice a week for only 6. weeks is safe and sufficient to induce DCM in rabbits. © 2012 Elsevier Ltd.