An evaluation of Vitamin E and Pycnogenol in children suffering from oral mucositis during cancer chemotherapy.

OBJECTIVE: The purpose of the present study was to evaluate and compare the effectiveness of Vitamin E (E) and Pycnogenol (P) in treatment of Chemotherapy-Related Oral Mucositis (ChROM) in children. MATERIALS AND METHODS: A total of 72 children, aged between 6 and 15 years, with ChROM were selected and randomly divided into three groups after assessment of oral mucositis (OM) by WHO grading system. Glycerine (control), E, and P were topically applied in group I, II, and III, respectively, and the prognosis of OM was assessed by functional, objective, and subjective parameters. RESULTS: Patients of group II and III showed significant improvement when ChROM was analyzed through scoring systems - WHO grading, Oral Mucositis Assessment Scale (OMAS), and Children's International Mucositis Evaluation Scale (ChIMES) as compared to group I (P < 0.001); however, there was no significant difference between groups II and III. CONCLUSION: Both the drugs E and P per se are effective for treatment of OM with P being not effective for the treatment of severe mucositis (grade 4). Combination of E and P and additional agents may be tried for better results.

A comparative evaluation of drops versus atomized administration of intranasal ketamine for the procedural sedation of young uncooperative pediatric dental patients: a prospective crossover trial.

OBJECTIVE: The objective of this study was to compare and evaluate the efficacy and safety of drops and atomized administration of intranasal ketamine (INK) in terms of behavioral response for agent acceptance during administration and for agent efficacy and safety for the sedation of young uncooperative pediatric dental patients. STUDY DESIGN: Thirty-four uncooperative ASA grade-1 children, requiring dental treatment were randomly assigned to receive INK as drops and atomized spray in one of the subsequent visit. This was a two stage cross-over trial and each child received INK by both modes of administration. The vital signs were monitored continuously during each visit. RESULTS: A statistically significant difference in patients acceptance (P < 0.0001) was observed in the atomized administration when compared to drops administration for the procedural event of drug administration. Moreover there were also significant differences (P < 0.05) between onset of sedation and recovery time between two groups. All the vital signs were within normal physiological limits and there were no significant adverse effects in either group. CONCLUSIONS: INK is safe and effective by either mode of intranasal (IN) drug administration for moderate sedation in facilitating dental care for anxious and uncooperative pediatric dental patients. Moreover, INK when administered with the mucosal atomization device, the acceptance of the drug was associated with less aversive reaction, rapid onset and recovery of sedation, as compared to the drop administration of the same agent.

A comparative evaluation of intranasal midazolam, ketamine and their combination for sedation of young uncooperative pediatric dental patients: a triple blind randomized crossover trial.

OBJECTIVE: The purpose of this study was to evaluate and compare the efficacy and safety of intranasal (IN) administration of midazolam (M), ketamine (K) and their combination (MK) to produce moderate sedation in young, uncooperative pediatric dental patients. STUDY DESIGN: In this three stage crossover trial forty five uncooperative ASA type-1 children, who required dental treatment, were randomly assigned to receive one of the three drugs/combination by IN route during three subsequent visits. The efficacy and safety of the agents were assessed by overall success rate and by monitoring of vital signs, respectively. RESULTS: The onset of sedation was rapid with K as compared to M and MK. The difference was statistically significant (P < 0.01) between K and M. The overall success rate was 89% with K, MK was 84% and 69% with M. The difference between the overall success rates of K and M was statistically significant (P < 0.01). Vital signs were within physiological limits and there were no significant adverse effects with any medication. CONCLUSIONS: M, K and MK are safe and effective by IN route to produce moderate sedation for providing dental care to pediatric dental patients who have been otherwise indicated for treatment under general anesthesia.

Midazolam-fentanyl analgo-sedation in pediatric dental patients--a pilot study.

OBJECTIVE: The objective of this study was to comparatively evaluate the effectiveness ofsubmucosalfentanyl when administered in conjunction with oral midazolam during pediatric procedural sedations. STUDY DESIGN: Twenty three uncooperative ASA type I children who met the selection criteria were randomly assigned to receive either submucosal fentanyl (3 microg/kg) or placebo, along with oral midazolam (0.5 mg/kg). A triple blind, 2-stage cross-over design was adopted so that each child received both the regimens. RESULTS: Transient oxygen desaturation was observed in 4 children who were sedated with the combination of oral midazolam and submucosalfentanyl. The overall success was 73.91% with oral midazolam and submucosal fentanyl regimen and 47.83% for oral midazolam and submucosal placebo regimen. The chances of 'satisfactorily'completing a 45 minute dental procedure in an uncooperative pediatric patient was 2.8 times more, when submucosalfentanyl was used along with oral midazolam. CONCLUSION: Submucosal fentanyl appears to improve the short working time associated with oral midazolam. But the oxygen desaturation associated with this regimen necessitates further studies to evaluate the efficacy of this combination at relatively lower doses before being used routinely for pediatric procedural sedation and analgesia.

A comparative evaluation of agents producing analgo-sedation in pediatric dental patients.

OBJECTIVE: Procedural sedation and analgesia (PSA) has reduced the need for general anesthesia (GA) for many surgical procedures in pediatric patients. The objective of this study was to evaluate the efficacy of four analgo-sedative combinations- midazolam plus ketamine (MK), midazolam plus tramadol (MT), promethazine plus tramadol (PT) and promethazine plus ketamine (PK) in facilitating dental treatment of uncooperative children. STUDY DESIGN: Thirty six uncooperative ASA type I children who required extensive dental treatment were randomly assigned to receive one of the four analgo-sedative combinations during each visit. A 4-stage cross-over design was adopted so that each child received all the four combinations. Safety was monitored through vital signs and side effects. RESULTS: The overall success was 81% with MK, 69% for PK, 67% for MT and 42% for PT and the difference between the success rates of these agents was statistically significant (p < 0.001). The required dental treatment could be successfully completed at least during 3 sessions in 23 children (62.2%). CONCLUSIONS: Segmental dental treatment under analgo-sedation can be considered as a viable alternative before considering patients for dental management under GA. MK and MT were found to be safe and effective for sedating pediatric dental patients.

Hepatitis C virus NS3-4A serine protease inhibitors: SAR of new P1 derivatives of SCH 503034.

Substitutions on the P(1) cyclobutyl side chain of SCH 503034 were studied by introduction of hydroxyl and fluoro substituents. Additionally, effects of fluoro substitution on other P1 moieties were evaluated.

Presence of opioid receptors in mesencephalic nucleus dorsalis raphe concerned in cardiovascular regulation in cats.

The effects of microinjection of opioid receptor agonist and antagonist into mesencephalic nucleus dorsalis raphe, were studied on mean arterial pressure and heart rate to elucidate the nature and role of these opioid receptors in cardiovascular regulation. Microinjection of morphine (5 micrograms and 10 micrograms) into nucleus dorsalis raphe elicited both inhibitory and excitatory cardiovascular responses respectively, while microinjection of opioid receptor antagonist, naloxone (10 micrograms) failed to produce any significant cardiovascular responses. However, local pretreatment with naloxone blocked both inhibitory and excitatory responses of graded doses of morphine. These opioid receptors seem to be localised in the neurons of the nucleus since microinjection of morphine into neural structures adjoining nucleus dorsalis raphe failed to induce any cardiovascular responses. Furthermore, the dose or morphine (2 micrograms) which was ineffective when microinjected into nucleus dorsalis raphe, produced inhibitory cardiovascular responses after pretreatment with LM5008, a 5-HT uptake blocker. Similarly, the excitatory cardiovascular responses of morphine microinjection were blocked by spinal cord transection (C1) and p-CPA, guanethidine and piperoxan pretreatments, while bilateral cervical vagotomy failed to do so. Thus, it is likely that the inhibitory cardiovascular responses of morphine are mediated directly through stimulation of opioid receptors present in the neurons of nucleus dorsalis raphe while the excitatory responses to higher dose of morphine, appear to be due to a release of noradrenaline which in turn modulates the activity of neurons by acting on alpha adrenoceptors.

Cardiovascular responses elicited by microinjection of monoamines into mesencephalic nucleus dorsalis raphe in cats.

The effect of monoaminergic agonists and antagonists microinjected into mesencephalic nucleus dorsalis raphe has been studied on blood pressure and heart rate to elucidate the nature and role of these monoaminergic receptors in cardiovascular regulation. Microinjection of monoamines, noradrenaline, phenylephrine and 5-hydroxytryptamine (5-HT) into nucleus dorsalis raphe elicited hypertension and tachycardia which could be blocked by local pretreatment with piperoxan (an alpha-adrenoceptor blocker) and methysergide (a 5-HT receptor blocker) respectively. However, isoprenaline microinjections failed to evoke any response. Bilateral vagotomy did not prevent these cardiovascular responses evoked by monoamines microinjection, while cervical spinal cord (C1) transection with bilateral vagotomy prevented these responses. These monoaminergic receptors seem to be localized in nucleus dorsalis raphe since microinjection of monoamines into neural structures adjoining nucleus dorsalis raphe, failed to induce any cardiovascular response. Monoaminergic receptors are present in nucleus dorsalis raphe which modulate cardiovascular activity by influencing sympathetic preganglionic neurons in the intermediolateral columns of the spinal cord.

A comparative evaluation of oral midazolam with other sedatives as premedication in pediatric dentistry.

The purpose of present study was to evaluate the safety and efficacy of orally administered midazolam in children as a sedative agent and to compare it with two other older agents, triclofos and promethazine. The study was conducted on ninety child patients requiring some short dental procedure. All the patients were with a good physical status (ASA-I). The ages ranged between 3 and 9 years. The patients were randomized into three study groups: Group 1, midazolam, Group II, triclofos and Group III, promethazine, on the basis of the drugs to be administered. After administration of drugs in each group, the effects were evaluated in terms of onset of action, sedative effect, ease of treatment completion, recovery time and postoperative amnesia. Midazolam was found to be the best drug among the three to produce conscious sedation in children.

Hepatitis C virus NS3-4A serine protease inhibitors: use of a P2-P1 cyclopropyl alanine combination for improved potency.

Modification of the P(2) and P(1) side chains of earlier P(3)-capped alpha-ketoamide inhibitor of HCV NS3 serine protease 1 resulted in the discovery of compound 24 with about 10-fold improvement in potency.

Hepatitis C virus NS3-4A serine protease inhibitors: SAR of P'2 moiety with improved potency.

We have discovered that introduction of appropriate amino acid derivatives at P'2 position improved the binding potency of P3-capped alpha-ketoamide inhibitors of HCV NS3 serine protease. X-ray crystal structure of one of the inhibitors (43) bound to the protease revealed the importance of the P'2 moiety.

Cardiovascular responses elicited by microinjection of cholinergic agents into nucleus dorsalis raphe in cats.

The effect of cholinomimetics and cholinoceptor blocking agents microinjected into nucleus dorsalis raphe (NDR) has been studied on heart rate and blood pressure to identify the nature and role of these cholinoceptors in cardiovascular regulation. Microinjection of the cholinoceptor agonists, pilocarpine and carbachol into NDR elicited bradycardia and hypotension accompanied by salivation which could be blocked by local pretreatment with ethybenztropine (a muscarinic receptor blocker), but not by chlorisondamine (a nicotinic receptor blocker). Pretreatment with atropine methylnitrate (i.v.), which blocks only peripheral muscarinic receptors, did not prevent these cardiovascular responses evoked by carbachol microinjection. These cholinergic receptors seem to be localized in NDR since, microinjection of carbachol into neural structures adjoining NDR, failed to induce any cardiovascular responses. Muscarinic cholinoceptors are present in NDR which modulate cardiovascular activity by influencing sympathetic preganglionic neurons in the intermediolateral columns of the spinal cord.

Chemical modifications and structure activity studies of ziracin and related everninomicin antibiotics.

Chemical modifications of eveminomicin antibiotics, particularly ziracin (1), were carried out to study the SARs as well as the chemical properties of this class of compounds. Use of allyl ether group for protection and selective deprotection of phenolic groups provided access to a variety of novel analogs of the title compounds, some of which exhibited the same high in vitro potency as the parent compounds.