Pentoxifylline has favorable preventive effects on experimental chronic pancreatitis model

Abstract

Background: To investigate the protective efficacy of pentoxifylline through biochemical parameters and histopathological scores in a caerulein- and alcohol-induced experimental model of chronic pancreatitis in rats.

Methods: A model of chronic pancreatitis with caerulein and alcohol was created in female rats of the genus Sprague Dawley. Pentoxifylline was administered in doses of 25?mg/kg (low dose) and 50?mg/kg (high dose) as a protective agent. Each group contained 8 animals. The groups were: group 1 (control group); caerulein?+?alcohol, group 2 (low-dose pentoxifylline group); caerulein?+?alcohol?+?pentoxifylline 25?mg/kg, group 3 (high-dose pentoxifylline group); caerulein?+?alcohol?+?pentoxifylline 50?mg/kg, group 4 (placebo); caerulein?+?alcohol?+?saline, group 5 (sham group); only saline injection.Rats were sacrificed 12?h after the last injection, and TNF-α, TGF-β, MDA, and GPx concentrations were measured in blood samples. The histopathologic examination was conducted by a pathologist who was unaware of the groups.

Results: The biochemical results of the treatment groups (group 2 and group 3) were statistically significantly lower compared with the control group (group 1) (p?<?.05). The difference between the low-dose treatment group (group 2) and high-dose treatment group (group 3) was significant in terms of biochemical parameters (p?<?.05). The difference between group 2 and the control group was not significant in terms of histopathologic scores (p?>?.05), whereas the difference between the group 3 and the control group was statistically significant (p?<?.05).

Conclusions: As a result, pentoxifylline, which has anti-inflammatory and antioxidant properties, was shown to have protective efficacy in an experimentally generated model of chronic pancreatitis.     

Topical analgesia following excisional haemorrhoidectomy: a systematic review and meta-analysis of randomised controlled trials

International Journal of Colorectal Disease - Post-operative pain following excisional haemorrhoidectomy poses a particular challenge for patient recovery, as well as a burden on hospital...     

Variability in Temperature-Related Mortality Projections under Climate Change

Background: Most studies that have assessed impacts on mortality of future temperature increases have relied on a small number of simulations and have not addressed the variability and sources of uncertainty in their mortality projections.Objectives: We assessed the variability of temperature projections and dependent future mortality distributions, using a large panel of temperature simulations based on different climate models and emission scenarios.Methods: We used historical data from 1990 through 2007 for Montreal, Quebec, Canada, and Poisson regression models to estimate relative risks (RR) for daily nonaccidental mortality in association with three different daily temperature metrics (mean, minimum, and maximum temperature) during June through August. To estimate future numbers of deaths attributable to ambient temperatures and the uncertainty of the estimates, we used 32 different simulations of daily temperatures for June–August 2020–2037 derived from three global climate models (GCMs) and a Canadian regional climate model with three sets of RRs (one based on the observed historical data, and two on bootstrap samples that generated the 95% CI of the attributable number (AN) of deaths). We then used analysis of covariance to evaluate the influence of the simulation, the projected year, and the sets of RRs used to derive the attributable numbers of deaths.Results: We found that < 1% of the variability in the distributions of simulated temperature for June–August of 2020–2037 was explained by differences among the simulations. Estimated ANs for 2020–2037 ranged from 34 to 174 per summer (i.e., June–August). Most of the variability in mortality projections (38%) was related to the temperature–mortality RR used to estimate the ANs.Conclusions: The choice of the RR estimate for the association between temperature and mortality may be important to reduce uncertainty in mortality projections.Citation: Benmarhnia T, Sottile MF, Plante C, Brand A, Casati B, Fournier M, Smargiassi A. 2014. Variability in temperature-related mortality projections under climate change. Environ Health Perspect 122:1293–1298; http://dx.doi.org/10.1289/ehp.1306954     

Efficacy of poly(adenosine diphosphate-ribose) polymerase inhibition in extracorporeal shock wave-induced renal injury

Objectives: Extracorporeal shock wave lithotripsy (ESW) induces renal damage by excessive production of free oxygen radicals. Free Oxygen radicals cause cellular injury by inducing nicks in DNA. The enzyme poly(adenosine diphosphate-ribose) polymerase (PARP) involved in the process of repair of DNA in damaged cells. However, its activation in damaged cells can lead to adenosine triphosphate depletion and death. Thus, we designed a study to evaluate the efficacy of 3-aminobenzamide (3-AB), a PARP inhibitor, against extracorporeal shock wave induced renal injury. Methods: Twenty-four Sprague-Dawley rats were divided into three groups: control, ESW, ESW?+?3-AB groups. All groups except control group were subjected to ESW procedure. ESW?+?3-AB group received 20?mg/kg/day 3-aminobenzamide intraperitoneally at 2?h before ESW and continued once a day for consecutive 3 days. The surviving animals were sacrificed at the 4th day and their kidneys were harvested for biochemical and histopathologic analysis. Blood samples from animals were also obtained. Results: Serum ALT and AST levels, serum neopterin and tissue oxidative stress parameters were increased in the ESW group and almost came to control values in the treatment group (p?p?Conclusion: Our data showed that PARP inhibition protected renal tissue against ESW induced renal injury. These findings suggest that it would be possible to improve the outcome of ESW induced renal injury by using PARP inhibitors as a preventive therapy.     

Does concomitant vaginal prolapse repair affect the outcomes of the transobturator tape procedure in the long term?

Introduction and hypothesis

Little information is available on the effects of concomitant vaginal prolapse repair on the outcomes of the transobturator tape (TOT) procedure. The purpose of this study is to assess the results and complications of TOT when combined with vaginal prolapse repair with a long-term follow-up.

Methods

We conducted a retrospective cohort study of 232 female patients who underwent the TOT procedure at two institutions. There were two groups: group 1 consisted of patients who had undergone TOT alone and group 2 consisted of patients who had undergone concomitant vaginal prolapse repair. The outcomes were analyzed considering four postoperative parameters: objective cure, subjective cure, resolution of urgency urinary incontinence (UUI), and patient satisfaction. The mean follow-up was 66.3 months (range 60–85).

Results

A total of 117 patients in group 1 and 104 patients in group 2 were documented in this study. The subjective and objective cure rates were 87.17 %, 64.95 % in group 1 and 89.42 %, 68.26 % in group 2. Patient satisfaction rates (visual analog scale [VAS] score ≥80) were 71.79 and 83.65 % in groups 1 and 2 respectively (p?=?0.035). Complications were reported according to the Clavien–Dindo classification with grade I 7.7 %, grade II 69.2 %, grade IIIa 7.7 %, and grade IIIb 15.4 %, and grade I 9.5 %, grade II 47.6 %, grade IIIa 42.8 %, and grade IIIb 0 % in groups 1 and 2 respectively.

Conclusions

Concomitant vaginal prolapse repair with TOT does not have any negative effects on continence outcomes; on the contrary, it increases patient satisfaction.     

Clinicopathologic and molecular features of intracranial desmoplastic small round cell tumors

Desmoplastic small round cell tumors (DSRCTs) are highly aggressive sarcomas that most commonly occur intra‐abdominally, and are defined by EWSR1‐WT1 gene fusion. Intracranial DSRCTs are exceptionally rare with only seven previously reported fusion‐positive cases. Herein, we evaluate the clinical, morphologic, immunohistochemical and molecular features of five additional examples. All patients were male (age range 6–25 years; median 11 years), with four tumors located supratentorially and one within the posterior fossa. The histologic features were highly variable including small cell, embryonal, clear cell, rhabdoid, anaplastic and glioma‐like appearances. A prominent desmoplastic stroma was seen in only two cases. The mitotic index ranged from <1 to 12/10 HPF (median 5). While all tumors showed strong desmin positivity, epithelial markers such as EMA, CAM 5.2 and other keratins were strongly positive in only one, focally positive in two and negative in two cases. EWSR1‐WT1 gene fusion was present in all cases, with accompanying mutations in the TERT promoter or STAG2 gene in individual cases. Given the significant histologic diversity, in the absence of genetic evaluation these cases could easily be misinterpreted as other entities. Desmin immunostaining is a useful initial screening method for consideration of a DSRCT diagnosis, prompting confirmatory molecular testing. Demonstrating the presence of an EWSR1‐WT1 fusion provides a definitive diagnosis of DSRCT. Genome‐wide methylation profiles of intracranial DSRCTs matched those of extracranial DSRCTs. Thus, despite the occasionally unusual histologic features and immunoprofile, intracranial DSRCTs likely represent a similar, if not the same, entity as their soft tissue counterpart based on the shared fusion and methylation profiles.     

Myxoid glioneuronal tumor,PDGFRA p.K385‐mutant: clinical,radiologic, and histopathologic features

“Myxoid glioneuronal tumor, PDGFRA p.K385‐mutant” is a recently described tumor entity of the central nervous system with a predilection for origin in the septum pellucidum and a defining dinucleotide mutation at codon 385 of the PDGFRA oncogene replacing lysine with either leucine or isoleucine (p.K385L/I). Clinical outcomes and optimal treatment for this new tumor entity have yet to be defined. Here, we report a comprehensive clinical, radiologic, and histopathologic assessment of eight cases. In addition to its stereotypic location in the septum pellucidum, we identify that this tumor can also occur in the corpus callosum and periventricular white matter of the lateral ventricle. Tumors centered in the septum pellucidum uniformly were associated with obstructive hydrocephalus, whereas tumors centered in the corpus callosum and periventricular white matter did not demonstrate hydrocephalus. While multiple patients were found to have ventricular dissemination or local recurrence/progression, all patients in this series remain alive at last clinical follow‐up despite only biopsy or subtotal resection without adjuvant therapy in most cases. Our study further supports “myxoid glioneuronal tumor, PDGFRA p.K385‐mutant” as a distinct CNS tumor entity and expands the spectrum of clinicopathologic and radiologic features of this neoplasm.