Taste alteration, mouth dryness and teeth staining as side effects of medications taken by elderly

Elderly patients generally use several types of medication, some of which may cause oral side effects. Aim: To investigate the oral side effects caused by medication in an elderly sample. Methods: Three hundred patients were interviewed about their use of medication and were divided in two groups: institutionalized (n=150) and community-dwelling (n=150) elderly. Results: The most used drugs were antihypertensives (53%) for community-dwelling elders and antiulceratives (76%) for the institutionalized ones. The more prevalent side effects were taste alterations that occurred in 19%, dry mouth in 17% and teeth staining in 2%. Conclusions: A high prevalence of oral side effects from medications used by the elderly was found in this study. The health professionals should be aware of the possible side effects caused by prescribed medications.

Effects of dipyrone, meloxicam, or the combination on hemostasis in conscious dogs

To compare the effects of dipyrone, meloxicam, and of the combination of these drugs on hemostasis in dogs. Prospective, blinded, randomized crossover study. Research laboratory at a veterinary teaching hospital. Six adult dogs. Animals received 4 intravenous treatments with 15-day washout intervals: control (physiological saline, 0.1 mL/kg), meloxicam (0.2 mg/kg), dipyrone (25 mg/kg), and dipyrone-meloxicam (25 and 0.2 mg/kg, respectively). A jugular catheter was placed for drug injection and for collecting samples for whole blood platelet aggregation (WBPA) and thromboelastometry assays at baseline, 1, 2, 3, 5, and 8 hours after treatment administration. The percent change from baseline of lag time and of the area under the curve (AUC) of impedance changes in response to collagen-induced platelet activation were recorded during WBPA. Thromboelastometry-derived parameters included clotting time, clot formation time, alpha-angle, and maximum clot firmness. The buccal mucosal bleeding time was evaluated by a blinded observer at baseline, 1, 3, and 5 hours after treatment injection. No significant changes in WBPA and thromboelastometry were recorded in the control treatment. Dipyrone significantly (P < 0.05) increased the lag time for 2 hours and decreased the AUC for 3 hours after injection. Meloxicam did not alter WBPA. Dipyrone-meloxicam significantly increased lag time for 2 hours and decreased the AUC for 5 hours after treatment injection. Experimental treatments did not differ from the control treatment for thromboelastometry and buccal mucosal bleeding time. While meloxicam does not alter hemostasis by the methods evaluated, dipyrone inhibits platelet aggregation for up to 3 hours. Meloxicam-dipyrone combination causes more prolonged inhibition of platelet function than dipyrone alone. Decreased platelet aggregation induced by dipyrone and dipyrone-meloxicam does not appear to impact the viscoelastic properties of the blood clot nor increase the risk of bleeding in dogs without preexisting hemostatic disorders.

Anti-inflammatory effects of Brazilian ginseng (Pfaffia paniculata) on TNBS-induced intestinal inflammation: experimental evidence

Inflammatory bowel disease (IBD) is a chronic, relapsing, idiopathic inflammation of the gastrointestinal tract. Clinical studies suggest that the initiation of IBD is multifactorial, involving genetics, the immune system and environmental factors, such as diet, drugs and stress. Pfaffia paniculata is an adaptogenic medicinal plant used in Brazilian folk medicine as an anti-stress agent. Thus, we hypothesised that the P. paniculata enhances the response of animals subjected to colonic inflammation. Our aim was to investigate the intestinal anti-inflammatory activity of P. paniculata in rats before or after induction of intestinal inflammation using trinitrobenzenesulfonic acid (TNBS). The animals were divided into groups that received the vehicle, prednisolone or P. paniculata extract daily starting 14days before or 7days after TNBS induction. At the end of the procedure, the animals were killed and their colons were assessed for the macroscopic damage score (MDS), extent of the lesion (EL) and weight/length ratio, myeloperoxidase (MPO) activity and glutathione (GSH), cytokines and C-reactive protein (CRP) levels. Histological evaluation and ultrastructural analysis of the colonic samples were performed. Treatment with the 200mg/kg dose on the curative schedule was able to reduce the MDS and the EL. In addition, MPO activity was reduced, GSH levels were maintained, and the levels of pro-inflammatory cytokines and CRP were decreased. In conclusion, the protective effect of P. paniculata was related to reduced oxidative stress and CRP colonic levels, and due to immunomodulatory activity as evidenced by reduced levels of IL-1β, INF-γ, TNF-α and IL-6.

Modulatory effects of propolis samples from Latin America (Brazil, Cuba and Mexico) on cytokine production by human monocytes

Propolis has been used in folk medicine in different regions of the world including Latin America. Propolis is a resinous mixture of substances collected by honey bees from several botanical sources, and its composition contains a rich chemical variety, depending on the geographical area and plant sources. Our aim was to compare the modulatory effect of propolis samples from three different countries of Latin America (Brazil, Cuba and Mexico) on pro- and anti-inflammatory cytokine production (tumor necrosis factor (TNF)-α and interleukin (IL)-10, respectively) by human monocytes. Cells were incubated with propolis for 18 h at 37°C. Cell viability was assessed by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide method, and cytokine production was determined by ELISA. All samples did not affect monocyte viability. Brazilian propolis stimulated both TNF-α and IL-10 production by monocytes. Cuban propolis stimulated TNF-α and inhibited IL-10 production, while Mexican sample exerted the opposite effect, inhibiting TNF-α and stimulating IL-10 production. The major compounds found in Brazilian, Cuban and Mexican propolis samples were artepillin C, isoflavonoids and pinocembrin, respectively. Brazilian, Cuban and Mexican propolis contained different components that may exert pro- and anti-inflammatory activity depending on concentration, what may provide a novel approach to the development of immunomodulatory drugs containing propolis.

Effects of 5-hydroxytryptophan and m-hydroxybenzylhydrazine associated to Lactobacillus spp. on the humoral response of broilers challenged with Salmonella Enteritidis

This study investigates the effects of different doses of serotonin, its precursor 5-hydroxytry-ptophan (5HTP), and m-hydroxybenzylhydrazine inhibitor (NSD1015), administered via intraperitoneal for 5 consecutive days, on behavior and average body weight of broilers. We also measured the humoral immune response and quantification of Salmonella Enteritidis in broilers chickens that received the drugs evaluated and a Lactobacillus pool. The study was divided into 3 experiments: Experiment 1--administration of pharmaceuticals with choice of dosage; Experiment 2--administration of pharmaceuticals and a Lactobacillus pool in birds that were not challenged with S. Enteritidis, and Experiment 3--administration of pharmaceuticals and a Lactobacillus pool in birds challenged with S. Enteritidis. The ELISA was used to scan dosages of intestinal IgA and serum IgY. We used colony-forming units to quantify S. Enteritidis. The concentrations of IgA and IgY did not show significant differences (P>0.05) in Experiment 2. In Experiment 3, NSD1015 associated with Lactobacillus determined higher IgA concentrations, promoting greater stimulus to the immune system than 5HTP. Regarding quantification of S. Enteritidis in the cecal content of birds, 5HTP associated to Lactobacillus determined the smallest number of bacteria, showing possible interaction of 5-hydroxytryptophan and Lactobacillus spp. with the immune system of broiler chickens.

Effects of nitric oxide synthesis inhibitor or fluoxetine treatment on depression-like state and cardiovascular changes induced by chronic variable stress in rats

Comorbidity between mood disorders and cardiovascular disease has been described extensively. However, available antidepressants can have cardiovascular side effects. Treatment with selective inhibitors of neuronal nitric oxide synthase (nNOS) induces antidepressant effects, but whether the antidepressant-like effects of these drugs are followed by cardiovascular changes has not been previously investigated. Here, we tested in male rats exposed to chronic variable stress (CVS) the hypothesis that nNOS blockers are advantageous compared with conventional antidepressants in terms of cardiovascular side effects. We compared the effects of chronic treatment with the preferential nNOS inhibitor 7-nitroindazole (7-NI) with those evoked by the conventional antidepressant fluoxetine on alterations that are considered as markers of depression (immobility in the forced swimming test, FST, decreased body weight gain and increased plasma corticosterone concentration) and cardiovascular changes caused by CVS. Rats were exposed to a 14-day CVS protocol, while being concurrently treated daily with either 7-NI (30 mg/kg) or fluoxetine (10 mg/kg). Fluoxetine and 7-NI prevented the increase in immobility in the FST induced by CVS and reduced plasma corticosterone concentration in stressed rats. Both these treatments also prevented the CVS-evoked reduction of the depressor response to vasodilator agents and baroreflex changes. Fluoxetine and 7-NI-induced cardiovascular changes independent of stress exposure, including cardiac autonomic imbalance, increased intrinsic heart rate and vascular sympathetic modulation, a reduction of the pressor response to vasoconstrictor agents, and impairment of baroreflex activity. Altogether, these findings provide evidence that fluoxetine and 7-NI have similar effects on the depression-like state induced by CVS and on cardiovascular function.

Experimental evidence of MAP kinase gene expression on the response of intestinal anti-inflammatory drugs

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

Experimental evidence of heparanase, Hsp70 and NF-κB gene expression on the response of anti-inflammatory drugs in TNBS-induced colonic inflammation

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

The effects of conjugated estrogen, raloxifene and soy extract on collagen in rat bones

Objective To evaluate the action of conjugated equine estrogen, raloxifene and isolated or combined genistein-rich soy extracts on collagen fibers in the bones of oophorectomized rats. Materials and methods Seventy female rats received testosterone propionate (0.1 mu g/g) on the 9th day after birth. At 6 months of age, the rats were administered the vehicle (propylene glycol, 0.5 ml/day), and ten of the rats were randomly chosen to comprise the non-oophorectomized control group (GI). The other 60 rats were ovariectomized and randomized into six groups of ten as follows: GII, vehicle; GIII, conjugated equine estrogen (CEE), 50 mu g/kg/day; GIV, raloxifene (RAL), 0.75 mg/kg/day; GV, genistein-rich soy extract (GSE), 300 mg/kg/day; GVI, CEE + GSE, 50 mu g/kg/day + 300 mg/kg/day; and GVII, CEE + RAL, 50 mu g/kg/day + 0.75 mg/kg/day. Three months after surgery, the drugs were administered for 60 consecutive days. All rats were euthanized, and their left tibiae were removed for histological routine. The histological sections were stained with hematoxylin-eosin, and picrosirius for evaluating bone microarchitecture. Types I and II collagen fibers were analyzed by immunofluorescence. Data analysis was carried out with ANOVA and Tukey's test. Results Collagen reduction was significant in the GIII animals when compared to the other groups (p < 0.05). There was no significant difference in the thickness of collagen fibers among the groups. There was a greater quantity of type III collagen in GVI than in the other groups. Conclusion Our data indicate that conjugated equine estrogen improves bone quality because it increases the quantity of type I collagen while reducing the quantity of thin collagen fibers. In addition, the combination of CEE and raloxifene or genistein-rich soy extract is not as efficient as CEE itself to improve bone quality.

Inhibition of iNOS induces antidepressant-like effects in mice: Pharmacological and genetic evidence

Recent evidence has suggested that systemic administration of non-selective NOS inhibitors induces antidepressant-like effects in animal models. However, the precise involvement of the different NOS isoforms (neuronal-nNOS and inducible-iNOS) in these effects has not been clearly defined yet. Considering that mediators of the inflammatory response, that are able to induce iNOS expression, can be increased by exposure to stress, the aim of the present study was to investigate iNOS involvement in stress-induced behavioral consequences in the forced swimming test (FST), an animal model sensitive to antidepressant drugs. Therefore, we investigated the effects induced by systemic injection of aminoguanidine (preferential iNOS inhibitor), 1400W (selective iNOS inhibitor) or n-propyl-L-arginine (NPA, selective nNOS inhibitor) in mice submitted to the FST. We also investigated the behavior of mice with genetic deletion of iNOS (knockout) submitted to the FST. Aminoguanidine significantly decreased the immobility time (IT) in the FST. 1400W but not NPA, when administered at equivalent doses considering the magnitude of their Ki values for iNOS and nNOS, respectively, reduced the IT, thus suggesting that aminoguanidine-induced effects would be due to selective iNOS inhibition. Similarly, iNOS KO presented decreased IT in the FST when compared to wild-type mice. These results are the first to show that selective inhibition of iNOS or its knockdown induces antidepressant-like effects, therefore suggesting that iNOS-mediated NO synthesis is involved in the modulation of stress-induced behavioral consequences. Moreover, they further support NO involvement in the neurobiology of depression. This article is part of a Special Issue entitled 'Anxiety and Depression'. (C) 2011 Elsevier Ltd. All rights reserved.

Comprehensive Evaluation of the Effects of Enalapril on Matrix Metalloproteinases Levels in Hypertension

Angiotensin-converting enzyme inhibitors (ACEi) may downregulate matrix metalloproteinases (MMPs). We examined whether enalapril affects MMP-2, MMP-8, and MMP-9 levels and activity, and their endogenous inhibitors (tissue inhibitors of MMPs, TIMP-1 and TIMP-2) levels in hypertensive patients. Moreover, we assessed the effects of enalaprilat on MMP-9 and TIMP-1 secretion by human endothelial cells (HUVECs). Thirty-eight hypertensive patients received enalapril for 8 weeks and were compared with thirty-eight normotensive controls. Blood samples were collected at baseline and after treatment. Plasma ACE activity was determined by a fluorimetric assay. Plasma MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 were measured by ELISA and gelatin zymography. A fluorogenic peptide cleavage assay was used to measure MMP activity. HUVECs cells were stimulated by phorbol-12-myristate-13-acetate (PMA) and the effects of enalaprilat (10(-10) to 10(-6) M) on MMP-9 and TIMP-1 levels were determined. Enalapril decreased blood pressure and ACE activity in hypertensive patients (P < 0.05), but had no effects on plasma MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 levels, or MMP activity. Enalaprilat had no effects on PMA-induced increases in MMP-9 and TIMP-1 secretion by HUVECs or on MMP activity. We show consistent evidence, both in vivo and in vitro, that enalapril does not affect MMPs and TIMPs levels in hypertensive patients.

Inhibition of nuclear factor-kappa B by dehydroxymethylepoxyquinomicin induces schedule-dependent chemosensitivity to anticancer drugs and enhances chemoinduced apoptosis in osteosarcoma cells

Osteosarcoma (OS) is the most common primary malignant bone tumor, usually developing in children and adolescents, and is highly invasive and metastatic, potentially developing chemoresistance. Thus, novel effective treatment regimens are urgently needed. This study was the first to investigate the anticancer effects of dehydroxymethylepoxyquinomicin (DHMEQ), a highly specific nuclear factor-kappa B (NF-kappa B) inhibitor, on the OS cell lines HOS and MG-63. We demonstrate that NF-kappa B blockade by DHMEQ inhibits proliferation, decreases the mitotic index, and triggers apoptosis of OS cells. We examined the effects of combination treatment with DHMEQ and cisplatin, doxorubicin, or methotrexate, drugs commonly used in OS treatment. Using the median effect method of Chou and Talalay, we evaluated the combination indices for simultaneous and sequential treatment schedules. In all cases, combination with a chemotherapeutic drug produced a synergistic effect, even at low single-agent cytotoxic levels. When cells were treated with DHMEQ and cisplatin, a more synergistic effect was obtained using simultaneous treatment. For the doxorubicin and methotrexate combination, a more synergistic effect was achieved with sequential treatment using DHMEQ before chemotherapy. These synergistic effects were accompanied by enhancement of chemoinduced apoptosis. Interestingly, the highest apoptotic effect was reached with sequential exposure in both cell lines, independent of the chemotherapeutic agent used. Likewise, DHMEQ decreased cell invasion and migration, crucial steps for tumor progression. Our data suggest that combining DHMEQ with chemotherapeutic drugs might be useful for planning new therapeutic strategies for OS treatment, mainly in resistant and metastatic cases. Anti-Cancer Drugs 23:638-650 (C) 2012 Wolters Kluwer Health broken vertical bar Lippincott Williams & Wilkins.

The effects on mucociliary clearance of prednisone associated with bronchial section

OBJECTIVE: Infections have been and remain the major cause of morbidity and mortality after lung transplantation. Because mucociliary clearance plays an important role in human defense mechanisms, the influence of drugs on the mucociliary epithelium of patients undergoing lung transplantation must be examined. Prednisone is the most important corticosteroid used after lung transplantation. The aim of this study was to evaluate the effects of bronchial transection and prednisone therapy on mucociliary clearance. METHODS: A total of 120 rats were assigned to 4 groups according to surgical procedure or drug therapy: prednisone therapy (1.25 mg/kg/day); bronchial section and anastomosis + prednisone therapy (1.25 mg/kg/day); bronchial section + saline solution (2 ml/day); and saline solution (2 ml/day). After 7, 15, or 30 days, the animals were sacrificed, and the lungs were removed from the thoracic cavity. The in situ mucociliary transport velocity, ciliary beat frequency and in vitro mucus transportability were evaluated. RESULTS: Animals undergoing bronchial section surgery and anastomosis had a significant decrease in the ciliary beat frequency and mucociliary transport velocity 7 and 15 days after surgery (p<0.001). These parameters were normalized 30 days after the surgical procedure. Prednisone improved mucous transportability in the animals undergoing bronchial section and anastomosis at 15 and 30 days (p<0.05). CONCLUSION: Bronchial section and anastomosis decrease mucociliary clearance in the early postoperative period. Prednisone therapy improves mucus transportability in animals undergoing bronchial section and anastomosis.

Infrared (810 nm) Low-Level Laser Therapy in Experimental Model of Strain-Induced Skeletal Muscle Injury in Rats: Effects on Functional Outcomes

Muscle strains are among the most prevalent causes for athletes absence from sport activities. Low-level laser therapy (LLLT) has recently emerged as a potential contender to nonsteroidal anti-inflammatory drugs in muscle strain treatment. In this work we investigated effects of LLLT and diclofenac on functional outcomes in the acute stage after muscle strain injury in rats. Muscle strain was induced by overloading the tibialis anterior muscle of rats during anesthesia. The injured groups received either no treatment, or a single treatment with diclofenac 30 min prior to injury, or LLLT (810 nm, 100 mW) with doses of 1, 3, 6 or 9 J, at 1 h after injury. Functional outcome measures included a walking index and assessment of electrically induced muscle performance. All treatments (except 9 J LLLT) significantly improved the walking index 12 h postinjury compared with the untreated group. The 3 J group also showed a significantly better walking index than the drug group. All treatments significantly improved muscle performance at 6 and 12 h. LLLT dose of 3 J was as effective as the pharmacological agent in improving functional outcomes in the early phase after a muscle strain injury in rats.

Protective effects of bone marrow mononuclear cell therapy on lung and heart in an elastase-induced emphysema model

We hypothesized that bone marrow-derived mononuclear cell (BMDMC) therapy protects the lung and consequently the heart in experimental elastase-induced emphysema. Twenty-four female C57BL/6 mice were intratracheally instilled with saline (C group) or porcine pancreatic elastase (E group) once a week during 4 weeks. C and E groups were randomized into subgroups receiving saline (SAL) or male BMDMCs (2 x 10(6), CELL) intravenously 3 h after the first saline or elastase instillation. Compared to E-SAL group, E-CELL mice showed, at 5 weeks: lower mean linear intercept, neutrophil infiltration, elastolysis, collagen fiber deposition in alveolar septa and pulmonary vessel wall, lung cell apoptosis, right ventricle wall thickness and area, higher endothelial growth factor and insulin-like growth factor mRNA expressions in lung tissue, and reduced platelet-derived growth factor, transforming growth factor-beta, and caspase-3 expressions. In conclusion, BMDMC therapy was effective at modulating the inflammatory and remodeling processes in the present model of elastase-induced emphysema. (c) 2012 Elsevier B.V. All rights reserved.