A double-blind, randomized controlled trial to compare the effectiveness and safety of purified protein derivative of tuberculin antigen with Mycobacterium w vaccine in the treatment of multiple viral warts.

BACKGROUND: Present day therapeutic modalities for viral warts are mostly ablative in nature, limited by high recurrence rates and are unsuitable for numerous lesions. Immunotherapy has the potential to overcome these limitations. AIMS: This study aimed at comparing efficacy and safety of and quality of life changes with intradermal purified protein derivative (PPD) of tuberculin antigen and Mycobacterium w (Mw) vaccine in immunotherapy of warts. METHODS: Patients with multiple (≥5) warts were randomized (1:1) into two groups (PPDand, Mw vaccine groups). Fortnightly, 0.1 ml of either medicine was injected intradermally over the deltoidregion till complete resolution or a maximum of six doses. Patients were followed-up for another 3 months for recurrence. RESULTS: Sixty-four participants received either PPD or Mw vaccine. The number of warts were comparable at baseline (P = 0.089, Mann-Whitney test), and reduced significantly with treatment in both groups (P < 0.001, Friedman's ANOVA), as seen from the fourth follow-up onwards with Mw and fifth follow-up onwards with PPD (P < 0.05, Post hoc Dunn's test). Intergroup comparison showed significantly more (P < 0.05, Mann-Whitney test) reduction with Mw than PPD at the sixth and seventh follow-up. The size of warts also reduced significantly (P < 0.001) in both groups from the third follow-up onwards. Complete remission was more (P = 0.539, Fischer's exact test) in the Mw group (68.8%) than the PPD group (50%); and was significantly higher (P = 0.049, Mann-Whitney test) in patients having shorter duration of warts. Adverse events were significantly more (P < 0.001) with Mw including ulceration (50%), discharge (15.6%), pain-swelling-induration and scar at the injection site (97% each), whereas some of those receiving PPD noted erythema and scaling at the injection site (18.8%), and post-inflammatory hyperpigmentation (12.5%). No recurrence was seen till the end of the study. LIMITATION: Unicentric trial. CONCLUSION: Intradermal injection of Mw vaccine was more effective but had a higher incidence of adverse effects compared to PPD of tuberculin antigen in patients with warts.

Anti-inflammatory effect of triterpene 3ß, 6ß, 16ß-trihydroxylup-20(29)-ene obtained from Combretum leprosum Mart & Eich in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The 3ß, 6ß, 16ß-trihydroxylup-20(29)-ene (TTHL) is a pentacyclic triterpene obtained from a medicinal plant named Combretum leprosum. In folk medicine, this plant is used to treat several diseases associated with inflammation and pain. We previously demonstrated that TTHL presents a significant antinociceptive effect, suggesting the involvement of the glutamatergic system. AIM OF THE STUDY: This study was designed to investigate the effect of TTHL on nociception and vascular permeability induced by acetic acid. We also evaluated the effect of TTHL on carrageenan-induced peritonitis and the levels of cytokines (interleukin 1-ß [IL-1ß], tumor necrosis factor α [TNF-α] and interleukin 10 [IL-10]) on peritoneal fluid. MATERIALS AND METHODS: TTHL was administered orally by intra-gastric gavage (i.g.) 60 min prior to experimentation. Abdominal contractions and vascular permeability were induced by an intraperitoneal (i.p.) injection of acetic acid (0.6%). We also investigated whether TTHL decreases carrageenan-induced peritonitis (750 µg/cavity) by measuring leukocyte migration and vascular permeability. In addition, we evaluated the effects of TTHL on TNF-α, IL-1ß and IL-10 release induced by carrageenan on peritoneal fluid. The levels of these cytokines were measured by ELISA. RESULTS: TTHL (0.01-10 mg/kg) administered by intra-gastric (i.g.) gavage inhibited (69±3%) acetic acid-induced abdominal constrictions, with an ID50 of 0.15 (0.03-0.8) mg/kg. TTHL (10mg/kg) also reduced the leukocyte infiltration induced by acetic acid, with an inhibition of 59±9 but had no effect on abdominal vascular permeability. In addition, indomethacin (10 mg/kg, i.p.) reduced the nociceptive behavior (92±1%), total leukocyte migration (29±3%) and capillary permeability (71±3%) induced by acetic acid. While the glucocorticoid dexamethasone (2 mg/kg, s.c.) reduced partially but significantly the nociception (31±1%), besides to promote a marked reduction on total leukocyte migration (60±2%) to the peritoneal cavity caused by acetic acid. In a model of peritonitis induced by carrageenan, TTHL also reduced total leukocyte migration, mainly neutrophils (inhibition of 84±3% and 85±2% at 30 mg/kg and 100 mg/kg, respectively). Likewise, dexamethasone (0.5 mg/kg, i.p.) resulted in an inhibition of 93±3%. Nevertheless, carrageenan-induced abdominal vascular permeability was reduced by dexamethasone but was not altered by TTHL. Furthermore, dexamethasone and TTHL significantly reduced the TNF-α and IL-1ß levels in peritoneal fluid, whereas the IL-10 levels were unchanged. CONCLUSIONS: Altogether, our data confirm the antinociceptive effect of TTHL and demonstrate its effect in inflammatory animal models, providing novel data about this compound, which could be useful as an anti-inflammatory drug.

Antinociceptive properties of the ethanolic extract and of the triterpene 3beta,6beta,16beta-trihidroxilup-20(29)-ene obtained from the flowers of Combretum leprosum in mice.

The present study examined the antinociceptive effects of the ethanolic extract (EE) and of the triterpene 3beta,6beta,16beta-trihidroxilup-20(29)-ene obtained from the flowers of Combretum leprosum in chemical and thermal behavioural models of pain in mice. The EE (10-1000 mg/kg) given orally (p.o.), 1 h prior to testing, produced dose-dependent inhibition of acetic acid-induced visceral pain, with mean ID50 value of 131.9 mg/kg. In the formalin test, the EE (10-300 mg/kg, p.o.) also caused significant inhibition of both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin-induced licking, however, it was more potent and efficacious in relation to the late phase of the formalin test, with mean ID50 values for the neurogenic and the inflammatory phases of approximately 300 and 88.8 mg/kg, respectively. The EE (10-1000 mg/kg, p.o.) also caused significant and dose-dependent inhibition of capsaicin- and glutamate-induced pain, with mean ID50 values of 160.5 and 38.3 mg/kg, respectively. Furthermore, the triterpene 3beta,6beta,16beta-trihidroxilup-20(29)-ene (1-30 mg/kg), given p.o., 1 h prior to testing, also produced dose-related inhibition of glutamate-induced pain, with a mean ID50 value of 5.6 mg/kg. When assessed in a thermal model of pain, the EE (10-300 mg/kg, p.o.) and fentanyl (100 microg/kg, s.c.) caused a significant and marked increase in the latency response on the hot-plate test (50 degrees C). The antinociception caused by EE (100 mg/kg, p.o.) in the glutamate test was significantly attenuated by intraperitoneal (i.p.) treatment of mice with naloxone (opioid receptor antagonist, 1 mg/kg), pindolol (a 5-HT 1A/1B receptor/beta adrenoceptor antagonist, 1 mg/kg), WAY100635 (a 5-HT 1A receptor antagonist, 0.7 mg/kg) or ketanserin (a 5-HT 2A receptor antagonist, 0.3 mg/kg). In contrast, EE (100 mg/kg, p.o.) antinociception was affected neither by L-arginine (precursor of nitric oxide, 600 mg/kg) nor by ondansetron (a 5-HT3 receptor antagonist, 0.5 mg/kg) i.p. treatment. It was not associated with non-specific effects such as muscle relaxation or sedation. Together, these results indicate that EE produces dose-related antinociception in several models of chemical and thermal pain through mechanisms that involve an interaction with opioid and serotonergic (i.e., through 5-HT 1A/1B and 5-HT 2A receptors) systems.

Capsaicin and the cause of causalgia.

From self-experimentation, I propose that the pain which occurs after application of capsaicin is causalgia and that this "capsaicin causalgia" is due to actual or functional depletion of neuropeptides such as substance P. This idea could provide an objective definition of the causalgic syndromes and improve the means of diagnosis. The analogy with capsaicin causalgia could also be extended to the pain of epidermal necrolysis, solar and thermal burns, and leprosy. The concept could lead to a better treatment of these causalgic syndromes by modulation of neuropeptide concentration or responsivity, or by mitigation of the consequences of its depletion.

Role of rifampicin in arthralgia induced by pyrazinamide

Arthralgia during daily treatment with chemotherapy regimens containing pyrazinamide was found to be considerably less in patients who received rifampicin concomitantly...