The Role of Topiramate in the Management of Cocaine Addiction: A Possible Therapeutic Option

Topiramate (TPM) is an antiepileptic drug able to play a role in both neurological and psychiatric disorders. TPM facilitates gamma-aminobutyric acid (GABA) transmission and inhibits glutamatergic transmission (i.e. AMPA/kainate receptors).Several studies reported that the modulation of GABAergic and glutamatergic synaptic transmission may reduce cocaine reinforcement. Therefore, TPM could be used in the management of cocaine dependence.     

Prognostic Value of p27, p53, and Vascular Endothelial Growth Factor in Dukes A and B Colon Cancer Patients Undergoing Potentially Curative Surgery

PURPOSE Early-stage colon cancer patients (Dukes A or B; pT1–T3 pNO pMO) are excluded from adjuvant chemotherapy following potentially curative surgery because they are expected to have good long-term survival. However, 20 percent to 30 percent of these patients ultimately succumb from recurrent disease. This indicates that the conventional staging procedures may be unable to precisely predict cancer prognosis.METHODS In 65 early-stage colon cancers, we investigated by immunohistochemistry the role of molecular markers such as p27, p53, and vascular endothelial growth factor in identifying high-risk patients who may benefit from adjuvant treatments.RESULTS No clinicopathologic factor, namely Dukes stage, t parameter, number of resected nodes, and vascular or lymphatic invasion, was found be an independent significant predictor of disease-specific and disease-free survival. In contrast, each molecular marker predicted survival and recurrence rates much better than the conventional Dukes staging system. The best combination of variables for prediction of long-term outcome and recurrence rate included p27, p53, and vascular endothelial growth factor. Interestingly, the greater the number of molecular alterations, the lower the five-year estimated survival function. Nearly all cancer-related deaths were observed among patients whose colon cancers expressed all three molecular alterations. Regardless of Dukes stage, the recurrence rate was found to increase with the increase in the number of molecular alterations. Early-stage colon cancers expressing p27 down-regulation and high p53 and vascular endothelial growth factor immunoreactivity showed a 100 percent actuarial four-year recurrence rate.CONCLUSIONS Assessment of molecular alterations may be useful to identify a higher-risk group of early-stage colon cancer patients who may benefit from adjuvant chemotherapy.     

Quantitative visualization of passive transport across bilayer lipid membranes

The ability to predict and interpret membrane permeation coefficients is of critical importance, particularly because passive transport is crucial for the effective delivery of many pharmaceutical agents to intracellular targets. We present a method for the quantitative measurement of the permeation coefficients of protonophores by using laser confocal scanning microscopy coupled to microelectrochemistry, which is amenable to precise modeling with the finite element method. The technique delivers well defined and high mass transport rates and allows rapid visualization of the entire pH distribution on both the cis and trans side of model bilayer lipid membranes (BLMs). A homologous series of carboxylic acids was investigated as probe molecules for BLMs composed of soybean phosphatidylcholine. Significantly, the permeation coefficient decreased with acyl tail length contrary to previous work and to Overton's rule. The reasons for this difference are considered, and we suggest that the applicability of Overton's rule requires re-evaluation.     

Allergic rhinitis phenotypes based on mono-allergy or poly-allergy

Inflammation Research - Allergic rhinitis (AR) is characterized by typical symptoms that are dependent on inflammation. Poly-allergy is a frequent phenomenon. Phenotyping AR represents an...     

Social Factors Associated with Readiness for Sexual Activity in Adolescents: A Population-Based Cohort Study

Archives of Sexual Behavior - Various factors are associated with sexual activity in adolescence and it is important to identify those that promote healthy and adaptive romantic and sexual...     

Synchronous colorectal cancer using CT colonography vs. other means: a systematic review and meta-analysis

Objectives

The objective of our study was to systematically review the evidence about synchronous colorectal cancer diagnosed with or without computed tomography colonography (CTC).

Materials and methods

Two systematic searches were performed (PubMed and EMBASE) for studies reporting the prevalence of synchronous colorectal cancer (CRC): one considering patients who underwent CTC and the another one considering patients who did not undergo CTC. A three-level analysis was performed to determine the prevalence of patients with synchronous CRC in both groups of studies. Heterogeneity was explored for multiple variables. Pooled prevalence and 95% confidence interval (CI) were calculated. A quality assessment (STROBE) was done for the studies.

Results

For CTC studies, among 2645 articles initially found, 21 including 1673 patients, published from 1997 to 2018, met the inclusion criteria. For non-CTC studies, among 6192 articles initially found, 27 including 111,873 patients published from 1974 to 2015 met the inclusion criteria. The pooled synchronous CRC prevalence was 5.7% (95% CI 4.7%–7.1%) for CTC studies, and 3.9% (95% CI 3.3%–4.4%) for non-CTC studies, with a significant difference (p = 0.004). A low heterogeneity was found for the CTC group (I² = 10.3%), whereas a high heterogeneity was found in the non-CTC group of studies (I² = 93.5%), and no significant explanatory variables were found. Of the 22 STROBE items, a mean of 18 (82%) was fulfilled by CTC studies, and a mean of 16 (73%) by non-CTC studies.

Conclusions

The prevalence of synchronous CRC was about 4–6%. The introduction of CTC is associated with a significant increase of the prevalence of synchronous CRCs.