Photobiomodulation therapy reduces apoptotic factors and increases glutathione levels in a neuropathic pain model

Neuropathic pain (NP) is caused by damage to the nervous system due to reactive oxygen spices (ROS) increase, antioxidants reduction, ATP production imbalance, and induction of apoptosis. In this investigation, we applied low-level laser 660 nm (photobiomodulation therapy) as a new strategy to modulate pain. In order to study the effects of photobiomodulation therapy (660 nm) on NP, chronic constriction injury (CCI) model was selected. Low-level laser of 660 nm was used for 2 weeks. Thermal and mechanical hyperalgesia were measured before and after surgery on days 7 and 14, respectively. Paw withdrawal thresholds were also evaluated. Expression of p2x3, Bax, and bcl2 protein was measured by western blotting. The amount of glutathione (GSH) was measured in the spinal cord by continuous spectrophotometric rate determination method. The results are presented as mean?±?SD. Statistical analysis of data was carried out using SPSS 21. CCI decreased the pain threshold, 2-week photobiomodulation therapy significantly increased mechanical and thermal threshold, decreased P2X3 expression (p?<?0.001), and increased bcl2 expression (p?<?0.01), but it was not effective on the Bax expression. We speculated that although photobiomodulation therapy increased ROS generation, it increased antioxidants such as GSH. Increase in bcl2 is another mitochondrial protection mechanism for cell survival and that pain relief and decrease in P2X3 expression confirm it.     

The role of MSX1 in tooth agenesis in Iranians

INTRODUCTION: MSX1 gene has a critical role in craniofacial development, the aim of this case-control study is to test the hypothesis that MSX1 mutation contributes to congenital tooth agenesis in Iranians. MATERIALS AND METHODS: The study group consisted of 20 affected individuals with tooth agenesis of lower second premolars or upper lateral incisors with mean age of 24.6. The control group consisted of 20 unaffected individuals. DNA was extracted from all 40 individuals; the polymerase chain reaction (PCR) for MSX1 was carried out with Phenol: Chloroform: Isoamylalchol (PCI) extraction method. Ban II restriction digest and agarose gel electrophoresis of the 20 affected individuals verified the presence of mutation in all 20 affected individuals. The unaffected controls did not show any mutation. Statistical analysis performed by the chi-squared method. RESULTS: Ban II did not digest PCR product (DNA) in the control group (195 bp band on electrophoresis gel) but digested the affected allele (106 bp and 89 bp bands). There is a statistically significant correlation between tooth agenesis and MSX1 mutation (P < 0.001). CONCLUSION: The results indicated that MSX1 gene mutation contributes to tooth agenesis in Iranian individuals. As the timing of tooth calcification can vary, radiographic finding of congenital tooth agenesis can be confirmed by this molecular method during different dental ages to achieve certainty.     

Site-specific, dose-dependent, and sex-related responses to the experimental pain model induced by intradermal injection of capsaicin to the foreheads and forearms of healthy humans

AIMS: To investigate whether trigeminal manifestations of pain, sensitization, and vasomotor responses following the intradermal injection of capsaicin to the foreheads differ from manifestations following injection of capsaicin in the forearms of healthy humans. Dose dependency and sex-related differences of the evoked responses were also studied. METHODS: Twenty-eight healthy volunteers (14 women, 14 men) participated in 2 separate experiments: (1) Features of pain and vasomotor responses following intradermal injection of capsaicin (100 microg/100 microL) to the forehead and forearm were compared. (2) The features after intradermal injection of 2 different doses of capsaicin (50, 100 microg/100 microL) to the forehead were also studied. In both experiments the effect of sex was also investigated. RESULTS: Experiment 1 showed that peak pain intensity (F [1,104] = 24.4, P < .001) and duration (F [1,104] = 13.3, P < .001) were greater in the forehead. However, the areas of visible flare (F [1,104] = 5.7, P < .05) and secondary pinprick hyperalgesia (F [1,104] = 155.1, P < .001) were significantly larger in the forearm. Experiment 2 indicated that peak pain intensity in the forehead was not affected by the capsaicin dose (F [1,52] = 1.6, P = .214), but duration of pain (F [1,52] = 6.0, P < .05) and perceived pain area (F [1,52] = 13.5, P < .001) were greater for the higher dose. The areas of visible flare (F [1,52] = 27.5, P < .001) and secondary pinprick hyperalgesia (F [1,52] = 65.6, P < .001) were also larger for the higher dose. In both experiments, women showed greater manifestations in several responses. CONCLUSION: Capsaicin-evoked sensory and vasomotor manifestations were different in the forehead and forearm. The differences are most likely due to the differences in innervation density and neurovascular activity. The capsaicin-induced effects were demonstrated to be dose-dependent and sex-related phenomena.     

Cyproterone acetate-loaded nanostructured lipid carriers: effect of particle size on skin penetration and follicular targeting

Cyproterone acetate (CPA) is used to treat various skin disorders such as acne, hirsutism, and alopecia. Due to the limited skin penetration of CPA, nanostructured lipid carriers (NLCs) with different size ranges were considered in this study in order to enhance skin penetration and to target hair follicles. Drug loading, drug release and morphological assessment were evaluated for each targeted size (100, 300, and 600?nm). Ex vivo skin penetration was also investigated using Franz diffusion cells. Finally, in vivo follicular targeting was evaluated using rhodamine B-loaded micro and nanoparticles. Results revealed that 60–85% of drug was slowly released from lipid nanoparticles within 72?h. CPA-NLC with average diameter of 600?nm had better penetration and deposition in dermis-epidermis layer, also CPA-NLC 100 and 300?nm significantly increased drug penetration in dermis-epidermis in comparison to free CPA. Follicular targeting results revealed that NLC 300?nm had the best accumulation capacity in hair follicles. CPA-NLC with average diameter of 300?nm could be a promising topical novel drug delivery system for specific targeting of hair follicles and sebaceous glands to treat androgenic skin disorders such as acne, hirsutism, and alopecia.     

The need for a paradigm shift in adherence research: The case of ADHD

Nonadherence to long-term medications attenuates optimum health outcomes. There is an abundance of research on measuring and identifying factors affecting medication adherence in a range of chronic medical conditions. However, there is a lack of standardisation in adherence research, namely in the methods and measures used. In the case of attention deficit hyperactivity disorder, this lack of standardisation makes it difficult to compare and combine findings and to draw meaningful conclusions. Standardisation should commence with a universally accepted categorisation or taxonomy of adherence which takes into consideration the dynamic nature of medication-taking. This should then be followed by the use of valid and reliable measures of adherence which can accurately quantify adherence at any of its phases, and provide useful information which can be utilised in planning targeted interventions to improve adherence throughout the patient medication-taking journey.     

Time Course Analysis of the Effects of Botulinum Neurotoxin Type A on Pain and Vasomotor Responses Evoked by Glutamate Injection into Human Temporalis Muscles

The effect of botulinum neurotoxin type A (BoNTA) on glutamate-evoked temporalis muscle pain and vasomotor responses was investigated in healthy men and women over a 60 day time course. Subjects participated in a pre-BoNTA session where their responses to injection of glutamate (1 M, 0.2 mL) and saline (0.2 mL) into the temporalis muscles were assessed. On Day 1, BoNTA (5 U) was injected into one temporalis muscle and saline into the contralateral temporalis muscle, in a randomized order. Subjects then received intramuscular injections of glutamate (1 M, 0.2 mL) into the left and right temporalis muscles at 3 h and subsequently 7, 30 and 60 days post-injection of BoNTA. Pain intensity, pain area, and neurogenic inflammation (skin temperature and skin blood perfusion) were recorded. Prior to BoNTA treatment, glutamate evoked significantly greater pain and vasomotor reactions (P < 0.001) than saline. BoNTA significantly reduced glutamate-evoked pain intensity (P < 0.05), pain area (P < 0.01), skin blood perfusion (P < 0.05), and skin temperature (P < 0.001). The inhibitory effect of BoNTA was present at 3 h after injection, peaked after 7 days and returned to baseline by 60 days. Findings from the present study demonstrated a rapid action of BoNTA on glutamate-evoked pain and neurogenic inflammation, which is in line with animal studies.     

What is patient adherence? A terminology overview

It is well known that patient adherence to appropriately prescribed medications is essential for treatment efficacy and positive therapeutic outcomes. It is also understood that patients who are prescribed medications do not necessarily take them as prescribed. Indeed, variation in patients' medication-taking is an age old conundrum which remains the focus of much interest amongst researchers and clinicians owing to its far-reaching consequences. Despite the extensive adherence-related research over the last four decades and a recent surge in this field, there remains a lack of uniformity in the terminology used to describe adherence and its related concepts. In turn, it is often difficult to conduct comparisons between adherence-related studies, which may be associated with the non-cumulative nature of work in this field. The purpose of this commentary is to provide an overview of key terminology relating to the field of adherence research.     

A humanized tissue-engineered in vivo model to dissect interactions between human prostate cancer cells and human bone

Currently used xenograft models for prostate cancer bone metastasis lack the adequate tissue composition necessary to study the interactions between human prostate cancer cells and the human bone microenvironment. We introduce a tissue engineering approach to explore the interactions between human tumor cells and a humanized bone microenvironment. Scaffolds, seeded with human primary osteoblasts in conjunction with BMP7, were implanted into immunodeficient mice to form humanized tissue engineered bone constructs (hTEBCs) which consequently resulted in the generation of highly vascularized and viable humanized bone. At 12 weeks, PC3 and LNCaP cells were injected into the hTEBCs. Seven weeks later the mice were euthanized. Micro-CT, histology, TRAP, PTHrP and osteocalcin staining results reflected the different characteristics of the two cell lines regarding their phenotypic growth pattern within bone. Microvessel density, as assessed by vWF staining, showed that tumor vessel density was significantly higher in LNCaP injected hTEBC implants than in those injected with PC3 cells (p < 0.001). Interestingly, PC3 cells showed morphological features of epithelial and mesenchymal phenotypes suggesting a cellular plasticity within this microenvironment. Taken together, a highly reproducible humanized model was established which is successful in generating LNCaP and PC3 tumors within a complex humanized bone microenvironment. This model simulates the conditions seen clinically more closely than any other model described in the literature to date and hence represents a powerful experimental platform that can be used in future work to investigate specific biological questions relevant to bone metastasis.