Synergistic interaction of fluconazole/sodium bicarbonate on the inhibition of Candida glabrata phospholipase gene

Abstract Candida glabrata infections are responsible for deaths of people globally. Fluconazole is known to be less effective against C. glabrata, which developed many strategies to evade being destroyed by fluconazole. To achieve enhanced efficacy of fluconazole against C. glabrata, the interaction of fluconazole with sodium bicarbonate was investigated using the CLSI guidelines. The efficacy of fluconazole alone and in combination with sodium bicarbonate was evaluated using the time-kill and phospholipase production assays. Eventually, the expression of PLB was assessed using semi-quantitative RT-PCR to investigate the inhibitory properties of fluconazole alone and in combination with sodium bicarbonate against C. glabrata. The fluconazole/sodium bicarbonate combination displayed synergistic and antagonistic effects (FICI= 0.375-4.25). In C. glabrata ATCC, SN 152, and SN 164, the fluconazole/sodium bicarbonate combination exhibited a significant fungicidal activity (p< 0.05) but antagonistic effect in the case of SN 283. With exception of SN 283, a significant reduction was noted in phospholipase production in clinical isolates of C. glabrata treated with fluconazole/sodium bicarbonate combination. The PLB was down-regulated significantly by 0.168-0.515 fold in C. glabrata treated with fluconazole/sodium bicarbonate. The results suggested fluconazole/sodium bicarbonate to have a potential synergistic interaction in C. glabrata, and the underlying mechanism may be associated with phospholipase gene

Improvement of dose distribution in ocular brachytherapy with 125I seeds 20-mm COMS plaque followed to loading of choroidal tumor by gold nanoparticles

Aims and Objectives: Brachytherapy using removable ophthalmic plaques loaded with suitable small sealed radioactive seeds adjacent to the ocular's tumor has been widely used as an effective treatment. The aim of this study was to investigate the dose distribution in a modeled eyeball followed to loading of an ocular melanoma tumor with different concentrations of gold nanoparticles (GNPs) as dose enhancement agent by Monte Carlo (MC) calculations. Materials and Methods: The MC code of MCNPX 2.6.0 was used to modeling of COMS standard eye plaque loaded with 24 125I sources (6711 model) located on the sclera of modeled eyeball with detailed structures and materials. A choroidal melanoma tumor was simulated and loaded with different concentrations of spherical gold GNPs (50 nm in diameter). Dose enhancement factors (DEFs) of ocular components were calculated. Results: The dosimetric properties of 125I source (6711 model) and dose distribution of COMS standard eye plaque were calculated successfully as recommended by TG-43U1; AAPM. Loading of tumor with GNPs increased dose to the tumor and decreased dose to the normal tissues; the DEF was increased up to 2.280 and 2.030 for tumor apex, while it was decreased to 0.760 and 0.892 for macula and for gold-tumor mixture and nanolattice distributions, respectively. Conclusion: Loading the choroidal tumor volume with GNPs improves the dose distribution by increasing dose to the tumor and decreasing dose to the health components in ocular brachytherapy with 125I seeds 20-mm COMS plaque

Role of rectal biopsy in predicting response to intrasphincteric botulinum toxin injection for obstructive symptoms after a pullthrough operation.

OBJECTIVE: Our aim was to correlate the pathological results and clinical response in patients who underwent botulinum toxin (BT) injection for obstructive symptoms (OS) after a pullthrough operation for Hirschsprung's disease (HD). METHODS: Between August 2002 and February 2006, 16 of 107 HD patients (15%) were referred with persistent OS after pull-through (PT) operation in this center. They underwent rectal biopsy and BT injection in the internal sphincter. Their responses to BT injection were evaluated by the constipation score before, and at 1, 3 and 8 months after the injection, and anorectal manometry (ARM) before and at 2 weeks, and 1 and 8 months after the injection. The association between response to BT and acetylcholinesterase (AChE) staining of rectal biopsy was also assessed. RESULTS: Fourteen of 16 patients (87%) had improvement in bowel function after 2 weeks, and two patients did not respond at all. Six of the 14 patients with early response had recurrence of symptoms after 2-3 months. Eight patients with normal ganglia and negative AChE had good response with no recurrence on follow-up. However, 4 of 6 recurrences were neurogenic dysfunctions and 2 were intestinal neuronal dysplasia (2-4+AChE). Two patients with no response had an aganglionic segment (4+AChE). Four of 6 patients with recurrence showed improvement with BT re-injection and only 2 did not improve. CONCLUSION: A higher degree of AChE staining is associated with lack of response to BT injection. This is also a test for predicting the severity of neurogenic dysfunction in the intestinal wall.

Comparison of botulinium toxin injection and posterior anorectal myectomy in treatment of internal anal sphincter achalasia.

OBJECTIVE: We compared the efficacy of intra-sphincteric botulinum toxin (BT) injection and posterior anorectal myectomy (PARM) for the treatment of internal anal sphincter achalasia (IASA). METHODS: Twenty eight of 120 patients (23%) with chronic constipation, who were referred to our clinic from September 2005 to December 2006, were evaluated. Patients had an absence of rectoanal inhibitory reflex on anorectal manometry (ARM) and showed no transitional region on barium enema. Fourteen patients each underwent rectal biopsy, and were treated with either intrasphincteric BT injection (Group I) or PARM (Group II). Nine patients were excluded because of absent ganglion cells on histology or positive acetylcholinesterase staining (AChE). The remaining 19 patients were followed up. All patients underwent ARM and constipation severity score (CSS) assessment 2 weeks before, and 1 and 6 months after the treatment. Patients were followed up telephonically at 12 months after treatment. RESULTS: Clinically good response was seen after 12 months in 3 patients each in Groups I and II. The median values of resting rectal pressure in Group I before and 6 months after BT injection were 60 mmHg and 40 mmHg (p< 0.0001), respectively, while in Group II the corresponding values were 60 mmHg and 45 mmHg (p< 0.0001), respectively. Compared to pre-treatment, median CSS improved in both Group I (14 to 13) and Group II (16 to 14) at 6 months after treatment (p< 0.0001 for both). However, there was no difference in resting rectal pressure and CSS between the groups. Three patients in Group II developed local abscess, postoperatively. CONCLUSIONS: BT injection has a similar efficacy as compared with PARM for the treatment of IASA, is less invasive and, is also associated with fewer complications.