Comparative evaluation of fluorinol and calcium sodium phosphosilicate-containing toothpastes in the treatment of dentin hypersensitivity.

BACKGROUND: Dentin hypersensitivity is one of the most commonly encountered clinical problems. Various desensitizing agents have been widely used in the management of dentin hypersensitivity. Fluorinol, a fluoride-containing agent, has shown to be effective in fluoridating the hydroxyapatite crystal and thus reduce enamel solubility. Calcium sodium phosphosilicate mechanically occludes open tubules and releases calcium and phosphorous to remineralize tooth structure. OBJECTIVE: To compare and assess the efficacy of fluorinol-containing toothpaste with 7.5% sodium calcium phosphosilicate-containing toothpaste in reducing dentin hypersensitivity. METHODOLOGY: Thorough oral prophylaxis was done, and the patients were subjected to the washout phase, after which they were randomly allocated to the two study groups, Group A-fluorinol-containing toothpaste, Group B-sodium calcium phosphosilicate-containing toothpaste. Patients were recalled on 2nd , 3rd and 4th weeks, and sensitivity was assessed using VAS scores by means of tactile, evaporative and cold water stimuli. Oral health-related quality of life was assessed using OHIP-14 questionnaire at baseline and 4 weeks. RESULT: Compared to baseline, there was a significant decrease in dentin hypersensitivity in both the groups. The VAS scores for tactile stimuli were significantly lower in group A at 3rd and 4th weeks. CONCLUSION: Fluorinol-containing toothpaste was shown to be effective in reducing dentinal hypersensitivity. Hence, it can be used routinely in the management of dentin hypersensitivity.

Synthesis, receptor binding, and CNS pharmacological studies of new thyrotropin-releasing hormone (TRH) analogues.

As part of our search for selective and CNS-active thyrotropin-releasing hormone (TRH) analogues, we synthesized a set of 44 new analogues in which His and pGlu residues were modified or replaced. The analogues were evaluated as agonists at TRH-R1 and TRH-R2 in cells in vitro, and in vivo in mice for analeptic and anticonvulsant activities. Several analogues bound to TRH-R1 and TRH-R2 with good to moderate affinities, and are full agonists at both receptor subtypes. Specifically, analogue 21 a (R=CH3) exhibited binding affinities (Ki values) of 0.17 µM for TRH-R1 and 0.016 µM for TRH-R2; it is 10-fold less potent than TRH in binding to TRH-R1 and equipotent with TRH in binding to TRH-R2. Compound 21 a, the most selective agonist, activated TRH-R2 with a potency (EC50 value) of 0.0021 µM, but activated TRH-R1 at EC50=0.05 µM, and exhibited 24-fold selectivity for TRH-R2 over TRH-R1. The newly synthesized TRH analogues were also evaluated in vivo to assess their potencies in antagonism of barbiturate-induced sleeping time, and several analogues displayed potent analeptic activity. Specifically, analogues 21 a,b and 22 a,b decreased sleeping time by nearly 50% more than TRH. These analogues also displayed potent anticonvulsant activity and provided significant protection against PTZ-induced seizures, but failed to provide any protection in MES-induced seizures at 10 µmol kg(-1). The results of this study provide evidence that TRH analogues that show selectivity for TRH-R2 over TRH-R1 possess potent CNS activity.

Characterization of anti-inflammatory properties and evidence for no sedation liability for the novel antihistamine SUN-1334H.

BACKGROUND: The anti-inflammatory potential of antihistamines has significant clinical utility. Long-term pharmacotherapy of so-called 'safe' antihistamines may be hampered by side effects in the central nervous system. In the present study, the new potential antihistamine SUN-1334H was compared with different antihistamines for anti-inflammatory effects, sedation potential and interaction with alcohol. METHOD: Nasal and skin allergy were induced in guinea pig and mice by ovalbumin sensitization and challenge. Neurogenic nasal inflammation was induced by capsaicin. Sedation potential and interaction with alcohol were assessed by i.v. and intracerebroventricular pentobarbital-induced sedation and alcohol-induced ataxia models. RESULTS: Ovalbumin sensitization and challenge caused rhinitis pathology including inflammatory cell infiltration, IL-4, and protein leakage in the nasal lavage fluid (NLF) and presence of inflammatory cells in nasal epithelium. A 5-day treatment of antihistamines reduced these markers of inflammation. SUN-1334H, cetirizine and hydroxyzine caused comparable inhibition of NLF leukocytes, IL-4 and total protein concentrations. Fexofenadine and desloratadine showed moderate inhibition of NLF leukocytes and had no significant effect on IL-4 concentration. While fexofenadine had no effect on total protein concentration, the effect of desloratadine was comparable with the other antihistamines. In neurogenic nasal inflammation induced by capsaicin, SUN-1334H and fexofenadine caused better inhibition at lower and middle dose levels than the other antihistamines. In skin allergy models, SUN-1334H showed potent reduction of passive and active cutaneous anaphylactic reactions. In central nervous system side effects models, SUN-1334H, desloratadine and fexofenadine were devoid of any significant effects. CONCLUSIONS: The results are suggestive of a high anti-inflammatory to sedation index of SUN-1334H among leading antihistamines.