Retinoic acid synergistically enhances the melanocytotoxic and depigmenting effects of monobenzylether of hydroquinone in black guinea pig skin

Monobenzylether of hydroquinone (MBEH) has long been utilized for the depigmentation therapy of patients with extensive vitiligo. In this approach, the normally pigmented areas surrounding vitiligo lesions are depigmented to achieve a uniform skin tone. One of the important disadvantages of MBEH therapy, however, is the resistance of a considerable number of vitiligo patients against the depigmenting effect of this agent. We have previously proposed that the glutathione-dependent cytoprotection of melanocytes can be impaired through the inhibition of the enzyme glutathione S-transferase by retinoic acid (RA). The combination of RA with melanocytotoxic agents could thus lead to increased susceptibility of melanocytes to such compounds. In this study we have shown, for the first time, that the melanocytotoxic and depigmenting effects of MBEH are synergistically enhanced when it is combined with RA. The treatment of black guinea pig skin with RA (0.025%) alone induced no significant changes in the number of epidermal melanocytes and no skin depigmentation. On the other hand, MBEH (10%) produced mild to moderate skin depigmentation and reduced the average number of melanocytes from 76 (+/-5)/field (magnification: x 40) in control sites, to 42 (+/-6)/field in the depigmented skin. The RA (0.025%)-MBEH (10%) combination, however, produced a complete degree of depigmentation in the majority of treated sites after 10 days of application and reduced the average number of melanocytes to only 6 (+/-6)/field. RA-MBEH combination serves as a very potent skin depigmenting formula and now awaits future assessments of its potential use for the treatment of extensive vitiligo.     

Do clinical and paraclinical findings have the power to predict critical conditions of injured patients after traumatic injury resuscitation?Using data mining artificial intelligence

Purpose The triage and initial care of injured patients and a subsequent right level of care is paramount for an overall outcome after traumatic injury.Early recognition of patients is an important case of such decision-making with risk of worse prognosis.This article is to answer if clinical and paraclinical signs can predict the critical conditions of injured patients after traumatic injury resuscitation.Methods The study included 1107 trauma patients,16 years and older.The patients were trauma victims of Levels I and II triage and admitted to the Rajaee(Emtiaz)Trauma Hospital,Shiraz,in 2014–2015.The cross-industry process for data mining methodology and modeling was used for assessing the best early clinical and paraclinical variables to predict the patients’prognosis.Five modeling methods including the support vector machine,K-nearest neighbor algorithms,Bagging and Adaboost,and the neural network were compared by some evaluation criteria.Results Learning algorithms can predict the deterioration of injured patients by monitoring the Bagging and SVM models with 99%accuracy.The most-fitted variables were Glasgow Coma Scale score,base deficit,and diastolic blood pressure especially after initial resuscitation in the algorithms for overall outcome predictions.Conclusion Data mining could help in triage,initial treatment,and further decision-making for outcome measures in trauma patients.Clinical and paraclinical variables after resuscitation could predict short-term outcomes much better than variables on arrival.With artificial intelligence modeling system,diastolic blood pressure after resuscitation has a greater association with predicting early mortality rather than systolic blood pressure after resuscitation.Artificial intelligence monitoring may have a role in trauma care and should be further investigated.     

Safety evaluation of mutagenicity,genotoxicity, and cytotoxicity of Lactobacillus spp. isolates as probiotic candidates

BackgroundProbiotics promote a healthy balance of gut bacteria and have many beneficial effects on human digestive physiology. Although, few side effects of probiotics have been reported. This study aimed to assess the safety of five probiotic candidate Lactobacillus strains isolated from healthy individuals by examining mutagenicity, genotoxicity, and oral toxic effects.MethodsFive selected candidate probiotic (SCPs) strains were evaluated for genotoxicity (Ames test with Salmonella typhimurium), in vitro mammalian chromosome aberration test and an in vivo mouse micronucleus assay on peripheral blood of mice. To evaluate the oral dose toxicity, BALB/c mice models were treated repeatedly (2000, 1000, and 500 mg/kg body weight /day) for 28‐days.ResultsThe Ames test performed for two S. typhimurium strains TA 98 and TA100 (both in the absence and in the presence of S‐9 metabolic activation system) did not show an increase in reverse mutation because of exposure to the SCPs in any of the doses (5.0, 2.5, 1.25, 0.625, and 0.3125 mg/plate). There was no genotoxicity in the SCPs treatment in the vitro chromosome aberration assay with Chinese hamster ovary cells (CHO‐K1). In addition, none of the tested strains increased the frequency of micronucleated reticulocytes in reticulocytes, the SCPs with the studied doses caused no substantial variation in the experimental groups compared to the negative control group (p > 0.05). SCPs were not acutely toxic when administered to male and female BALB/c mice by single gavage at (2000, 1000, and 500 mg/kg b.w/day) with no mortality or clinical signs, change in body weight or macroscopic abnormalities were observed in this dose range.ConclusionAs a result, SCPs did not induce mutagenic potential in vitro with bacterial reverse mutation, clastogenicity, and in vivo tests in the ranges of concentrations evaluated in our study.     

Lack of evidence for <Emphasis Type="Italic">Helicobacter pylori</Emphasis> to prevent children growth efficiently

We have read with great interest an article by Kocaoglu et al published in May issue of the World Journal of Pediatrics.[1] A total of 243 children aged between 8-18 years were examined based on growth determinants and existence of Helicobacter pylori (H.pylori) colonization in Turkey.The conclusion of this research is that H.pylori colonization affected children growth;and the longer duration of infection,the worse effect on growth.     

Effects of patellar taping on knee pain,functional disability,and patellar alignments in patients with patellofemoral pain syndrome: A randomized clinical trial

Question

What are the effects of patellar taping on pain, functional disability and patellar alignments in Patellofemoral Pain Syndrome (PFPS)?

Nano-based strategies to overcome p-glycoprotein-mediated drug resistance

Introduction: The discussion about cancer treatment has a long history. Chemotherapy, one of the promising approaches in cancer therapy, is limited in the clinic as plenty of factors evolve and prevent appropriate therapeutic response to drugs. Multi-drug resistance (MDR), which is mostly P-glycoprotein-mediated, is described as the most well-known impediment in this contribution. It extrudes several agents out of cells, arising MDR and decreasing the bioavailability of drugs. Hence, cancer cells become insensitive to chemotherapy.

Areas covered: Many agents have been developed to reverse MDR, but it is difficult to deliver them into cancer sites and cancer cells. The emerging nano-based drug delivery systems have been more effective to overcome P-glycoprotein-mediated MDR by increasing the intracellular delivery of these agents. Here, we represent systems including siRNA-targeted inhibition of P-gp, monoclonal antibodies, natural extracts, conventional inhibitors, hard nanoparticles and soft nanoparticles as delivery systems in addition to a novel approach applying cell penetrating peptides.

Expert opinion: Overcoming cancer drug resistance using innovative nanotechnology is being increasingly used and developed. Among resistance mechanisms, drug efflux transporter inhibitors and MDR gene expression silencing are among the those being investigated. In the near future, it seems some of these nanomedical approaches might become the mainstay of effective treatment of important human conditions like cancer.