Antibiotic combination therapy in patients with chronic, treatment-resistant pouchitis

BACKGROUND: Pouchitis is the major long-term complication after ileal pouch-anal anastomosis for ulcerative colitis. About 15% of patients have a chronic, treatment-resistant disease. AIMS: To evaluate the efficacy of an antibiotic combination for chronic active, treatment-resistant pouchitis. PATIENTS AND METHODS: Eighteen patients were treated orally with rifaximin 1 g b.d. + ciprofloxacin 500 mg b.d. for 15 days. Symptoms assessment, endoscopic and histological evaluations were performed at screening and after 15 days using the Pouchitis Disease Activity Index (PDAI). Improvement was defined as a decrease of at least 3 points in PDAI score, and remission as a PDAI score of 0. Systemic absorption of rifaximin was determined by high performance liquid chromatography. Faecal samples were collected before and after antibiotic treatment for stool culture. RESULTS: Sixteen out of 18 patients (88.8%) either improved (n=10) or went into remission (n=6); the median PDAI scores before and after therapy were 11 (range 9-17) and 4 (range 0-16), respectively (P < 0.002). No side-effects were reported. Rifaximin plasma levels and urinary excretion were negligible, confirming its mainly topical activity. A significant decrease in total anaerobes and aerobes, enterococci, lactobacilli, bifidobacteria and bacteroides in faecal samples was observed, while the reduction in number of coliforms and Clostridium perfringens did not reach a statistical significance. CONCLUSIONS: A combination of rifaximin and ciprofloxacin was effective in patients with active chronic, treatment-resistant pouchitis, suggesting the need, in these patients, for treatment using antibiotic agents with wide antibacterial spectrum of activity.     

Memory and the septo-hippocampal cholinergic system in the rat

This study examined the effects of intrahippocampal injections of scopolamine (a muscarinic antagonist drug) on performance of a working-memory task (contingently) reinforced T-maze alternation) and a reference-memory task (visual discrimination) by the same rats in the same maze. Rats in the first shipment were trained in delayed alternation, received bilateral implantation of cannulae aimed at the CA3 field of the dorsal hippocampus, and were tested for retention with 1 l microinjections of scopolamine (35 g) and saline on alternate days. These rats were then trained on visual discrimination and tested alternately under scopolamine or saline as described above. It was found that scopolamine impaired performance of delayed alternation to a greater extent than performance of visual discrimination. Data from rats in the second shipment replicated this finding, with the order of the tasks reversed, and, additionally, showed that delayed alternation, but not visual discrimination, was impaired at a dose of 12 g/l. A dose of 4 g/l had no effect on either task. It is concluded that performance of a workingmemory task is significantly more sensitive to disruption of cholinergic mechanisms in the hippocampus than performance of a reference-memory task.Supported by PHS Training Grant MH-14577. Now at the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA     

Mutagenic activity in waste from an aluminum products factory in Salmonella/microsome assay

The mutagenic activity of waste material originating from an aluminum products factory was determined by the Salmonella/microsome assay, using the bacterial strains TA100, TA98 and YG1024. The material was obtained by sweeping the factory floor at the end of the work shift. Organic compounds were extracted by ultrasound for 30 min in dichloromethane or 70% ethanol. After evaporation of solvent, these extracts were dissolved in dimethylsulfoxide, and tested for the mutagenic activity at varying concentrations. All the extracts from the factory had mutagenic activity, especially in the YG1024 strain, suggesting the presence of aromatic amines, later confirmed by chemical analysis. The TA98 strain also showed mutagenic activity, though it did not exhibit the highest mutagenicity index observed with the YG1024 strain. In TA100, mutagenic activity was not observed. This study should serve as an alert to management and those who are occupationally exposed, and as a warning that this type of waste should not be discarded in the environment without any control.     

Evidence of zinc deficiency in competitive swimmers

ObjectiveThe aim of this study was to assess the nutritional zinc (Zn) status of elite swimmers during different training periods.MethodsA longitudinal paired study was performed at the University of Sao Paulo in eight male swimmers 18 to 25 y old who had been swimming competitively at the state and national levels for at least 5 y. The swimmers were evaluated over a total period of 14 wk: before the basic and specific preparatory period (BSPP-baseline), at the end of the basic and specific preparatory period (post-BSPP), and at the end of the polishing period (PP). Levels of Zn were determined in the plasma, erythrocyte, urine, and saliva by atomic absorption spectrophotometry. Anthropometric measurements and a 3-d food record were also evaluated.ResultsThe median plasma Zn concentration was below the reference value in all training periods (BSPP-baseline 59 μg/dL, post-BSPP 55.9 μg/dL, after PP 58.8 μg/dL, P > 0.05), as were threshold values for erythrocytes (BSPP-baseline 36.5 μg of Zn/g of hemoglobin, post-BSPP 42 μg of Zn/g of hemoglobin, after PP 40.7 μg of Zn/g of hemoglobin, P > 0.05), urinary Zn (BSPP-baseline 280 μg/24 h, post-BSPP 337 μg/24 h, after PP 284 μg/24 h, P > 0.05), and salivary Zn (BSPP-baseline 66.1 μg/L, post-BSPP 54.1 μg/L, after PP 79.7 μg/L, P > 0.05). Salivary Zn did not correlate with plasma and erythrocyte Zn levels.ConclusionThe results suggest that the elite swimmers studied presented a possible Zn deficiency and that salivary Zn was not adequate to evaluate the Zn nutritional status.     

PARP inhibitor rucaparib induces changes in NAD levels in cells and liver tissues as assessed by MRS

Poly(adenosine diphosphate ribose) polymerases (PARPs) are multifunctional proteins which play a role in many cellular processes. Namely, PARP1 and PARP2 have been shown to be involved in DNA repair, and therefore are valid targets in cancer treatment with PARP inhibitors, such as rucaparib, currently in clinical trials. Proton magnetic resonance spectroscopy (¹H‐MRS) was used to study the impact of rucaparib in vitro and ex vivo in liver tissue from mice, via quantitative analysis of nicotinamide adenosine diphosphate (NAD⁺) spectra, to assess the potential of MRS as a biomarker of the PARP inhibitor response. SW620 (colorectal) and A2780 (ovarian) cancer cell lines, and PARP1 wild‐type (WT) and PARP1 knock‐out (KO) mice, were treated with rucaparib, temozolomide (methylating agent) or a combination of both drugs. ¹H‐MRS spectra were obtained from perchloric acid extracts of tumour cells and mouse liver. Both cell lines showed an increase in NAD⁺ levels following PARP inhibitor treatment in comparison with temozolomide treatment. Liver extracts from PARP1 WT mice showed a significant increase in NAD⁺ levels after rucaparib treatment compared with untreated mouse liver, and a significant decrease in NAD⁺ levels in the temozolomide‐treated group. The combination of rucaparib and temozolomide did not prevent the NAD⁺ depletion caused by temozolomide treatment. The ¹H‐MRS results show that NAD⁺ levels can be used as a biomarker of PARP inhibitor and methylating agent treatments, and suggest that in vivo measurement of NAD⁺ would be valuable.     

Long-Term Outcome and Prognostic Factors After Spontaneous Cerebellar Hemorrhage

Cerebellar hemorrhage is the least common type of intracranial hemorrhage (ICH) encountered in clinical practice, and clinical data concerning the long-term outcomes are limited. This study aimed to investigate the long-term outcomes following spontaneous cerebellar hemorrhage in a cohort of Chinese patients. This single-center observational study was carried out between 1996 and 2010 and included 72 consecutive Chinese patients with a first spontaneous cerebellar hemorrhage. Of 440 patients with primary ICH, 72 (16.4%) had primary cerebellar hemorrhage. The mean age was 67.5?±?12.3?years and patients were predominantly male (54%). The 30-day mortality was 16.7% with Glasgow coma scale ??8 as the only predictor. At 6?months, 56.7% of patients who survived the first 30?days had a persistently poor functional status with modified Rankin scale score >2. After a mean follow-up of 4.7?years, 3.3% of patients had recurrent ICH, a recurrence rate of 7.3 per 1,000 patient-years. Ischemic stroke occurred in 12% of patients, an incidence of 25.5 per 1,000 patient-years. This study provided data on the long-term outcome of post-cerebellar hemorrhage in Chinese patients.