S-nitrosoglutathione decreases inflammation and bone resorption in experimental periodontitis in rats

Background: S‐nitrosoglutathione (GSNO) is a nitric oxide donor that may exert antioxidant, anti‐inflammatory, and microbicidal actions and is thus a potential drug for the topical treatment of periodontitis. In this study, the effect of intragingival injections of GSNO‐containing polyvinylpyrrolidone (PVP) formulations is evaluated in a rat model of periodontitis. Methods: Periodontal disease was induced by placing a sterilized nylon (000) thread ligature around the cervix of the second left upper molar of the animals, which received intragingival injections of PVP; saline; or PVP/GSNO solutions which corresponded to GSNO doses of 25, 100, and 500 nmol; 1 hour before periodontitis induction, and thereafter, daily for 11 days. Results: PVP/GSNO formulations at doses of 25 and/or 100, but not 500 nmol caused significant inhibition of alveolar bone loss, increase of bone alkaline phosphatase, decrease of myeloperoxidase activity, as well as significant reduction of inflammatory and oxidative stress markers when compared to saline and PVP groups. These effects were also associated with a decrease of matrix metalloproteinases 1 and 8, inducible nitric oxide synthase, and nuclear factor‐κB immunostaining in the periodontium. Conclusion: Local intragingival injections of GSNO reduces inflammation and bone loss in experimental periodontal disease.     

Physical therapy and anesthetic blockage for treating temporomandibular disorders: A clinical trial

Purpose: the aim of this study was to evaluate the use of physical therapy and anesthetic blockage of the auriculotemporal nerve as a treatment for temporomandibular joint disorders. Methods: the sample comprised of twenty patients with a diagnosis of disc displacement with/ without reduction and arthralgia according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD Axis I Group IIa, IIb and IIIa). Ten patients (group 1) underwent a cycle of eight anesthetic blockages of the auriculotemporal nerve with injections (1 per week) of 1 ml of bupivacaine 0.5% without vasoconstrictor for 8 weeks. The other 10 patients (group 2) received anesthetic blockage and physical therapy (massage and muscular stretching exercises). After the end of treatment all patients were evaluated at baseline, 1st week, 4th week and 2 months. The t-Student and F (ANOVA) tests were used for statistical analysis, with a significance rate of 5%. Results: there was a significant difference when both groups were compared according to VAS score (p=0.027). There was no significant difference for the other variables: MMO and jaw protrusion. Conclusion: the anesthetic blockage and physical therapy, when used together, are effective in the reduction of pain in patients with TMD. Key words:Temporomandibular joint disorders, physical therapy, physiotherapy and nerve block, local anesthetic, bupivacaine.     

Epidural spinal cord stimulation plus quipazine administration enable stepping in complete spinal adult rats

We hypothesized that epidural spinal cord stimulation (ES) and quipazine (a serotonergic agonist) modulates the excitability of flexor and extensor related intraspinal neural networks in qualitatively unique, but complementary, ways to facilitate locomotion in spinal cord-injured rats. To test this hypothesis, we stimulated (40 Hz) the S(1) spinal segment before and after quipazine administration (0.3 mg/kg, ip) in bipedally step-trained and nontrained, adult, complete spinal (mid-thoracic) rats. The stepping pattern of these rats was compared with control rats. At the stimulation levels used, stepping was elicited only when the hindlimbs were placed on a moving treadmill. In nontrained rats, the stepping induced by ES and quipazine administration was non-weight bearing, and the cycle period was shorter than in controls. In contrast, the stepping induced by ES and quipazine in step-trained rats was highly coordinated with clear plantar foot placement and partial weight bearing. The effect of ES and quipazine on EMG burst amplitude and duration was greater in flexor than extensor motor pools. Using fast Fourier transformation analysis of EMG bursts during ES, we observed one dominant peak at 40 Hz in the medial gastrocnemius (ankle extensor), whereas there was less of dominant spectral peak in the tibialis anterior (ankle flexor). We suggest that these frequency distributions reflect amplitude modulation of predominantly monosynaptic potentials in the extensor and predominantly polysynaptic pathways in the flexor muscle. Quipazine potentiated the amplitude of these responses. The data suggest that there are fundamental differences in the circuitry that generates flexion and extension during locomotion.     

Novel isomannide-based peptide mimetics containing a tartaric acid backbone as serine protease inhibitors

Hepatitis C viral infection is a cause of chronic liver disease, and current therapies are only effective in 50 % of patients. Serine proteases, which are present in both hepatitis C virus (HCV) and the dengue virus, are the most studied class of proteolytic enzymes and are the primary targets for drug development in this field. In this paper, we describe the synthesis of a novel class of isomannide-based peptide mimetic compounds based on a tartaric acid backbone. Our data showed that substitutions at position 168 (D168A) and 170 (V170A) conferred low-level resistance against compound 5a3, whereas substitutions at position 155 (R155K) and 156 (A156V) conferred no resistance. These data suggest that even though compound 5a3 is a noncompetitive inhibitor; it is able to interact with important residues located near the catalytic site. In addition, this novel compound class exhibits potent antiviral activity against variants carrying resistance mutations to boceprevir and telaprevir. Our docking studies showed important interactions, including hydrogen bonds and a π–π interaction, between compound 5a3 and residues of the allosteric site of NS3/4A. Biological and theoretical results indicate that 5a3 is a promising lead compound for the development of new drugs targeting HCV infection.