Exogenous Administration of 15d-PGJ(2)-Loaded Nanocapsules Inhibits Bone Resorption in a Mouse Periodontitis Model

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Serum magnesium levels in healthy dogs submitted to the administration of cisplatin with fluid therapy

Cisplatin is an antineoplastic drug that is used to treat carcinomas and osteosarcomas in dogs. However, it can cause kidney damage which in turn leads to the loss of electrolytes. Concentration of magnesium was evaluated in the blood serum of eight dogs that had undergone therapy with cisplatin. The dogs were divided into two groups. Group 1 was supply with cisplatin (70 mg/m(2), iv) and to prevent nephrotoxcity, saline solution at 0.9% was administered (25 ml/kg/hour, iv in three hours). The animals in Group 2 were not supplied with cisplatin. There was no significant difference (P < 0.05) between the two groups and the results obtained indicated that the protocol used for Group 1 did not cause changes in the serum concentrations of magnesium. Therefore, it can be concluded that the administration of cisplatin does not cause variations if it is combined with the fluid therapy.

Preliminary Study of the Gastric Acidity in Thoroughbred Horses at Rest after Enteral Administration of Esomeprazole Magnesium (Nexium)

The regulation of gastric secretion is of crucial importance to the equilibrium of the gastroenteric system. Despite the large number of factors involved in the causes of peptic illnesses, pH = 4 is considered the threshold between physiologic and deleterious effects of stomach acid secretion. With the aim of maintaining pH greater than 4, proton-pump inhibitors, such as esomeprazole magnesium (NEXIUM), have shown excellent results in the control of acid secretion. Aimed at examining the action of this drug in the control of pH levels of gastric secretion in thoroughbreds, a single dose of 40 or 80 mg of esomeprazole magnesium was administered daily, and pH was determined serially for 5 consecutive days. The results obtained corroborated the efficacy of esomeprazole magnesium in the control of gastric pH at both doses tested, with 100% of the mean pH being greater than 5. Moreover, no statistical difference was noted between the two doses tested.

Anxiety-induced antinociception in mice: effects of systemic and intra-amygdala administration of 8-OH-DPAT and midazolam

Rationale: Mice exhibit antinociception after a single experience in the elevated plus maze (EPM), an animal model of anxiety. Objective: This study investigated the mechanisms involved in this form of anxiety-induced antinociception. Methods: Nociception was evaluated by means of the writhing test in mice confined either to the open or enclosed arms of the EPM. The effects of systemic (naloxone, midazolam and 8-OH-DPAT) or intra-amygdala (8-OH-DPAT. NAN-190 and midazolam) drug infusions were investigated in mice previously treated i.p. with 0.6% acetic acid, an algic stimulus that induces abdominal contortions. The effects of these drugs on conventional measures of anxiety (% entries and % time in open arms) in a standard EPM test were also independently investigated. Results: Open-arm confinement resulted in a high-magnitude antinociception (minimum 85%, maximum 450%) compared with enclosed arm confinement. The opiate antagonist naloxone (1 mg/kg and 10 mg/kg) neither blocked this open arm-induced antinociception (OAIA) nor modified indices of anxiety in EPM. Administration of midazolam (0.5-2 mg/kg, s.c.) increased OAIA and produced antinociception in enclosed confined animals, as well as attenuating anxiety in the EPM. The 5-HT(1A) receptor agonist 8-OH-DPAT (0.05-1 mg/kg, s.c.) had biphasic effects on OAIA, antagonising the response at the lowest dose and intensifying it at the highest dose. In addition, low doses of this agent reduced anxiety in the EPM. Although bilateral injections of 8-OH-DPAT (5.6 nmol/0.4 mu l) or NAN-190 (5.6 nmol and 10 nmol/0.4 mu l) into the amygdala did not alter OAIA, increased anxiety was observed in the EPM. In contrast, intra-amygdala administration of midazolam (10 nmol and 30 nmol/0.4 mu l) blocked both OAIA and anxiety. Conclusions: These results with systemic and intracerebral drug infusion suggest that 5-HT(1A) receptors localised in the amygdala are not involved in the pain inhibitory processes that are recruited during aversive situations. However, activation of these receptors does phasically increase anxiety. Although the intrinsic antinociceptive properties of systemically administered midazolam confounded interpretation of its effects on OAIA, intra-amygdala injections of this compound suggest that benzodiazepine receptors in this brain region modulate both the antinociceptive and behavioural (anxiety) responses to the EPM.

Differential behavioral and neuroendocrine effects of repeated nicotine in adolescent and adult rats

Despite the high prevalence of tobacco abuse among adolescents, the neurobiology of nicotine addiction has been studied mainly in adult animals. Repeated administration of this drug to adult rats induces behavioral sensitization. Nicotine activates the HPA axis in adult rats as measured by drug-induced increases in ACTH and corticosterone. Both behavioral sensitization and corticosterone are implicated in drug addiction. We examined the expression of behavioral sensitization induced by nicotine as well as the changes in corticosterone levels after repeated injections of nicotine in adolescent and adult animals. Adolescent and adult rats received subcutaneous (s.c.) injections of saline or 0.4 mg/kg of nicotine once daily for 7 days. Three days after the last injection animals were challenged with saline or nicotine (0.4 mg/kg; s.c.). Nicotine-induced locomotion was recorded in an activity cage. Trunk blood samples were collected in a subset of adolescent and adult rats and plasma corticosterone levels were determined by radioimmunoassay. Adult, but not adolescent, rats expressed behavioral sensitization. Pretreatment with nicotine abolished corticosterone-activating effect of this drug only in adult animals, indicating the development of tolerance at this age. Our results provide evidence that adolescent rats exposed to repeated nicotine display behavioral and neuroendocrine adaptations distinct from that observed in adult animals. (c) 2004 Elsevier B.V. All rights reserved.

Comparative effects of acute and subacute lycopene administration on chromosomal aberrations induced by cisplatin in male rats

Lycopene is a natural carotenoid, free radical scavenger, and presents protective effects by inhibiting oxidative DNA damage. The objective of the current study was to investigate the cytogenetic effects of a single acute and four daily gavage administrations of lycopene, and to examine possible protective effects on chromosomal damage induced by the antitumor drug cisplatin (cDDP) in rat bone marrow cells. The animals were divided into treatment groups, with three lycopene doses in the acute treatment (2, 4, and 6 mg/kg b.w.), three lycopene doses in the subacute treatment (0.5, 1.0, and 1.5 mg/kg b.w.) with and without cDDP (5 mg/kg b.w. i.p.), and respective controls. The results indicated that lycopene is neither cytotoxic nor clastogenic when compared with the negative controls (P > 0.01). cDDP-treated animals submitted to acute and subacute treatments with different lycopene doses showed a significant reduction (p < 0.01) in the number of abnormal metaphases when compared with the animals treated only with cDDP. The protective effects of lycopene on cDDP-induced chromosomal damage may be attributed to its antioxidant activity. These results suggest that this carotenoid may prove useful in reducing some of the toxic effects associated with certain classes of chemotherapeutic agents. (c) 2006 Elsevier Ltd. All rights reserved.

Controlled transscleral drug delivery formulations to the eye: establishing new concepts and paradigms in ocular anti-inflammatory therapeutics and antibacterial prophylaxis

Importance of the field: The use of topical agents poses unique and challenging hurdles for drug delivery. Topical steroids effectively control ocular inflammation, but are associated with the well-recognized dilemma of patient compliance. Although administration of topical antimicrobials as prophylaxis is acceptable among ophthalmologists, this common practice has no sound evidence base Developing a new antimicrobial agent or delivery strategy with enhanced penetration by considering the anatomical and physiological constraints exerted by the barriers of the eye is not a commonly perceived strategy. Exploiting the permeability of the sclera, subconjunctival routes may offer a promising alternative for enhanced drug delivery and tissue targeting.Area covered in this review: Ocular drug delivery strategies were reviewed for ocular inflammation and infections clinically adopted for newer class of antimicrobials, which use a multipronged approach to limit risks of endophthalmitis.What the reader will gain: The analysis substantiates a new transscleral drug delivery therapeutic approach for cataract surgery.Take home message: A new anti-inflammatory and anti-infective paradigm that frees the patient from the nuisance of topical therapeutics is introduced, opening a large investigative avenue for future improved therapies.

Rheological, mechanical and mucoadhesive properties of thermoresponsive, bioadhesive binary mixtures composed of poloxamer 407 and carbopol 974P designed as platforms for implantable drug delivery systems for use in the oral cavity

This study described the formulation and characterisation of the viscoelastic, mechanical and mucoadhesive properties of thermoresponsive, binary polymeric systems composed of poloxamer (P407) and poly(acrylic acid, C974P) that were designed for use as a drug delivery platform within the oral cavity. Monopolymeric and binary polymeric formulations were prepared containing 10, 15 and 20% (w/w) poloxamer (407) and 0.10-0.25% (w/w) poly(acrylic acid, 934P). The flow theological and viscoelastic properties of the formulations were determined using controlled stress and oscillatory rheometry, respectively, the latter as a function of temperature. The mechanical and mucoadhesive properties (namely the force required to break the bond between the formulation and a pre-hydrated mucin disc) were determined using compression and tensile analysis, respectively. Binary systems composed of 10% (w/w) P407 and C934P were elastoviscous, were easily deformed under stress and did not exhibit mucoadhesion. Formulations containing 15 or 20% (w/w) Pluronic P407 and C934P exhibited a sol-gel temperature T(sol/gel), were viscoelastic and offered high elasticity and resistance to deformation at 37 degrees C. Conversely these formulations were elastoviscous and easily deformed at temperatures below the sol-gel transition temperature. The sol-gel transition temperatures of systems containing 15% (w/w) P407 were unaffected by the presence of C934P; however, increasing the concentration of C934P decreased the T(sol/gel) in formulations containing 20%(w/w) P407. Rheological synergy between P407 and C934P at 37 degrees C was observed and was accredited to secondary interactions between these polymers, in addition to hydrophobic interactions between P407 micelles. Importantly, formulations composed of 20% (w/w) P407 and C934P exhibited pronounced mucoadhesive properties. The ease of administration (below the T(sol/gel)) in conjunction with the viscoelastic (notably high elasticity) and mucoadhesive properties (at body temperature) render the formulations composed of 20% (w/w) P407 and C934P as potentially useful platforms for mucoadhesive, controlled topical drug delivery within the oral cavity. (c) 2009 Published by Elsevier B.V.

Social defeat stress in rats: escalation of cocaine and speedball binge self-administration, but not heroin

Exposure to intermittent episodes of social defeat stress can increase drug seeking and leads to intense drug taking in rats.This study investigated the consequences of repeated, intermittent social defeat stress on patterns of drug self-administration in rats with access to heroin, cocaine, or a heroin-cocaine combination (speedball).Male Long-Evans rats were either handled (controls) or subjected to 25-min social defeat stress episodes on days 1, 4, 7, and 10 during confrontations with an aggressive resident. Ten days following the last defeat, rats were assessed for locomotor cross-sensitization in response to heroin or cocaine. Animals were then prepared with intrajugular catheters for drug self-administration. Separate groups of controls and defeated rats were examined for self-administration of heroin (experiment 1), a heroin-cocaine combination (experiment 2), or cocaine (experiment 3). Drug self-administration patterns were evaluated using fixed or progressive ratio schedules of reinforcement during limited access sessions or a 24-h unlimited access binge.Rats with a history of intermittent social defeat stress showed sensitized locomotor behavior when challenged with heroin or cocaine relative to controls. During the 24-h binge session, defeated rats escalated cocaine-taking behavior (ca. 110 mg/kg vs. 66 mg/kg in controls), persisted in self-administering cocaine or the heroin-cocaine mixture for more hours, and showed a tendency for increased heroin-cocaine intake, but no effects on heroin taking.A history of social defeat stress seems to preferentially promote escalated intake of cocaine but not heroin, unless a heroin-cocaine combination is available.

Repeated exposure of adolescent rats to oral methylphenidate does not induce behavioral sensitization or cross-sensitization to nicotine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Repeated administration of caffeine induces either sensitization or tolerance of locomotor stimulation depending on the environmental context

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of subcutaneous methadone, morphine, buprenorphine or saline on thermal and pressure thresholds in cats

This study compared pressure and thermal thresholds after administration of three opioids in eight cats. Pressure stimulation was performed via a bracelet taped around the forearm. Three ball-bearings were advanced against the forearm by inflation of a modified blood pressure bladder. Pressure in the cuff was recorded at the end point (leg shake and head turn). Thermal threshold was tested as previously reported using a heated probe held against the thorax [Dixon et al. (2002) Research in Veterinary Science, 72, 205]. After baseline recordings, each cat received subcutaneous methadone 0.2 mg/kg, morphine 0.2 mg/kg, buprenorphine 0.02 mg/kg or saline 0.3 mL in a four period cross-over study. Measurements were made at 15, 30, 45 min and 1, 2, 3, 4, 8, 12 and 24 h after the injection. Data were analysed by ANOVA (P < 0.05). There were no significant changes in thresholds after saline. Thermal threshold increased at 45 min after buprenorphine (maximum 2.8 +/- 3 degrees C), 1-3 h after methadone (maximum 3.4 +/- 1.9 degrees C) and 45 min to 1 h (maximum 3.4 +/- 2 degrees C) after morphine. Pressure threshold increased 30-45 min (maximum 238 +/- 206 mmHg) after buprenorphine, 45-60 min after methadone (maximum 255 +/- 232 mmHg) and 45-60 min and 3-6 h (maximum 255 +/- 232 mmHg) after morphine. Morphine provided the best analgesia, and methadone appears a promising alternative. Buprenorphines limited effect was probably related to the subcutaneous route of administration. Previously, buprenorphine has produced much greater effects when given by other routes.

Clinical and Histological Effects of the Intrathecal Administration of Methylprednisolone in Dogs

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Evaluation of the adverse effects of subcutaneous carprofen over six days in healthy cats

This study evaluated the adverse effects of carprofen in seven healthy cats. Values for CBC, biochemical profiles and platelet aggregation were measured before and at seven days after SID treatment with subcutaneous carprofen: 4 mg/kg (day 1), 2 mg/kg (day 2 and 3) and 1 mg/kg (day 4 and 6) (CG) or 0.35 ml of saline (SG) for six days in a randomized, blinded, cross-over study with a four-week washout period. No treatment was given on day 5. Endoscopy of the GI tract was performed pre-treatment and on day 7 post-treatment. There were no significant changes in hematological profiles, biochemical profiles and endoscopy grading scores within nor between groups, except for lower albumin values at baseline than on day 7 (CG), and globulin and ALP values were higher at baseline than on day 7 in CG and SG. SC administration of carprofen over six days did not cause any adverse effects on gastrointestinal, hematological, or serum biochemical variables. (c) 2008 Elsevier Ltd. All rights reserved.