Clofazimine in Mycobacterium abscessus peritonitis: A pediatric case report.

Peritonitis- and catheter-related infections due to nontuberculous mycobacteria (NTM) including Mycobacterium abscessus have been reported among adults on peritoneal dialysis (PD). There is no recommended antimicrobial regimen for the treatment of M. abscessus peritonitis. Clofazimine has emerged as an important adjuvant antimicrobial treatment of M. abscessus lung infection. We report, to our knowledge, the first case of M. abscessus PD peritonitis in a child treated successfully using clofazimine as a novel adjuvant therapy to amikacin and clarithromycin. Her clinical features were similar to those of bacterial peritonitis, but she had persistence of symptoms and high inflammatory markers despite empirical therapy for peritonitis. Bacterial culture of PD effluent became positive for M. abscessus after 5 days. There was complete symptom resolution after 6 days of multidrug therapy. Due to ototoxicity, amikacin was discontinued after 6 weeks, while clarithromycin and clofazimine were continued for 9 months to ensure complete pathogen eradication before a planned renal transplant. A high index of suspicion in refractory or culture-negative cases is important for the diagnosis of NTM peritonitis. Multidrug therapy is recommended for M. abscessus infections. Clofazimine was chosen as a novel adjunct antimicrobial because of its pharmacokinetics, ease of administration, cost-effectiveness, and lack of serious adverse events.

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.

Preoperative CT staging in sigmoid diverticulitis--does it correlate with intraoperative and histological findings?

PURPOSE: This study was designed to evaluate whether the computed tomography (CT) reflects the extent of the inflammation in sigmoid diverticulitis (SD) in order to draw conclusions for selecting the appropriate treatment. METHODS: Two hundred four patients who underwent resection for SD from January 2003 to December 2008 were included. The preoperative CT stage was compared with intraoperative and histological findings. Patients were classified into phlegmonous (Hansen-Stock IIa), abscess-forming (HS IIb), and free perforated (HS IIc) forms of SD. Patients with a recurrent type of diverticulitis were excluded. RESULTS: In the phlegmonous type (HS IIa; n = 75), we found a correlation with the preoperative stage in 52% (intraoperative) and 56% (histological), an understaging in 12% (intraoperative) and 11% (histological), and an overstaging in 36% (intraoperative) and 33% (histological). In the abscess-forming type (HS IIb, Hinchey I/II; n = 87), we found conformity in 92% (intraoperative) and 90% (histological), understaging in 3% (intraoperative) and 0% (histological), and overstaging in 5% (intraoperative) and 10% (histological). In the presence of a free perforation (HS IIc, Hinchey III/IV; n = 42), we saw conformity in 100% (intraoperative and histological). The positive predictive value for correctly diagnosing of phlegmonous type (HS IIa), abscess-forming type (HS IIb), and free perforation (HS IIc) by CT was intraoperatively (histologically) 52% (56), 92% (90), and 100% (100), respectively. CONCLUSIONS: The CT is one of the most accurate methods for staging in SD. However, in the phlegmonous type (HS IIa), it leads to an overestimation of the findings in every third patient. It must be clarified whether this pronounced low inflammation should really be regarded as a complicated form of SD. In contrast, the abscess-forming (HS IIb) and free perforated (HS IIc) type of complicated SD is very well reflected by CT.

Involvement of NO in the inhibitory effect of Calotropis procera latex protein fractions on leukocyte rolling, adhesion and infiltration in rat peritonitis model.

AIM OF THE STUDY: The latex of Calotropis procera has been used in the traditional medicinal system for the treatment of leprosy, ulcers, tumors, piles and diseases of liver, spleen, abdomen and toothache. It comprises of a non-dialyzable protein fraction (LP) that exhibits anti-inflammatory properties and a dialyzable fraction (DF) exhibiting pro-inflammatory properties. The present study was carried out to evaluate the effect of LP sub-fractions on neutrophil functions and nociception in rodent models and to elucidate the mediatory role of nitric oxide (NO). MATERIAL AND METHODS: The LP was subjected to ion exchange chromatography and the effect of its three sub-fractions (LP(PI), LP(PII) and LP(PIII)) thus obtained was evaluated on leukocyte functions in the rat peritonitis model and on nociception in the mouse model. RESULTS: LP sub-fractions exhibit distinct protein profile and produce a significant decrease in the carrageenan and DF induced neutrophil influx and exhibit anti-nociceptive property. The LP and its sub-fractions produced a marked reduction in the number of rolling and adherent leukocytes in the mesenteric microvasculature as revealed by intravital microscopy. The anti-inflammatory effect of LP(PI), the most potent anti-inflammatory fraction of LP, was accompanied by an increase in the serum levels of NO. Further, our study shows that NO is also involved in the inhibitory effect of LP(PI) on neutrophil influx. CONCLUSIONS: Our study shows that LP fraction of Calotropis procera comprises of three distinct sets of proteins exhibiting anti-inflammatory and anti-nociceptive properties of which LP(PI) was most potent in inhibiting neutrophil functions and its effects are mediated through NO production.