Comparative effectiveness of Low Level Laser therapy and Transcutaneous Electric Nerve Stimulation on Temporomandibular Joint Disorders

Background: Temporomandibular joint disorders are the most common source of pain on the face. There are multiple etiologies, and several types of treatment have been reported. The use of non-invasive and reversible therapies in the treatment of such problems is recommended. The present study evaluated the effect of low level laser (LLL) therapy and transcutaneous electric nerve stimulation (TENS) on temporomandibular joint disorders. Methods: In this single-blind study, 40 patients with temporomandibular disorders were randomly divided into four groups: TENS (TENSTem dental), LLL (diode 810 nm CW), sham-TENS, and sham-LLL. All subjects were examined and data on pain and tenderness in the temporomandibular joint (TMJ) and masticatory muscles (using the visual analogue scale) and mouth-opening (distance between incisal edges before feeling pain; mm) were collected before baseline (T1), after each session (T2-T5) and one month after the end of the sessions (T6)), and analyzed using repeated measure ANOVA and Boneferronie statistical tests. A p-value < 0.05 was considered significant. Results: The decrease in pain (p = 0.000), tenderness (p = 0.000) and increase in mouth-opening ability (p = 0.002) was greater in the TENS and LLL groups than in the placebo groups. At the one-month follow-up, significant decrease in pain and tenderness was recorded in the TENS and LLL groups (p = 0.000). There was no significant differences between TENS and LLL and the placebo groups for maximum mouth-opening at the end of the study (p = 0.692). Conclusion: Using TENS or LLL therapy can improve TMD symptoms at least for the short term. Although the effects of the placebo played a role in improving symptoms, their effects were less importan

Nanocarriers call the last shot in the treatment of brain cancers

Our brain is protected by physio-biological barriers. The blood–brain barrier (BBB) main mechanism of protection relates to the abundance of tight junctions (TJs) and efflux pumps. Although BBB is crucial for healthy brain protection against toxins, it also leads to failure in a devastating disease like brain cancer. Recently, nanocarriers have been shown to pass through the BBB and improve patients’ survival rates, thus becoming promising treatment strategies. Among nanocarriers, inorganic nanocarriers, solid lipid nanoparticles, liposomes, polymers, micelles, and dendrimers have reached clinical trials after delivering promising results in preclinical investigations. The size of these nanocarriers is between 10 and 1000 nm and is modified by surface attachment of proteins, peptides, antibodies, or surfactants. Multiple research groups have reported transcellular entrance as the main mechanism allowing for these nanocarriers to cross BBB. Transport proteins and transcellular lipophilic pathways exist in BBB for small and lipophilic molecules. Nanocarriers cannot enter via the paracellular route, which is limited to water-soluble agents due to the TJs and their small pore size. There are currently several nanocarriers in clinical trials for the treatment of brain cancer. This article reviews challenges as well as fitting attributes of nanocarriers for brain tumor treatment in preclinical and clinical studies

Preparation, characterization, and biodistribution of glutathione PEGylated nanoliposomal doxorubicin for brain drug delivery with a post-insertion approach

Objective(s): Brain cancer treatments have mainly failed due to their inability to cross the blood-brain barrier. Several studies have confirmed the presence of glutathione (GSH) receptors on BBB’s surface, as a result, products like 2B3-101, which contain over 5% pre-inserted GSH PEGylated liposomal Doxorubicin, are being tested in clinical trials. Here we conducted the PEGylated nanoliposomal Doxorubicin particles that are covalently attached to the glutathione using the post-insertion technique. Compared with the pre-insertion approach, the post-insertion method is notably simpler, faster, and more cost-effective, making it ideal for large-scale pharmaceutical manufacturing. Materials and Methods: The ligands of the DSPE PEG(2000) Maleimide-GSH were introduced in the amounts of 25, 50, 100, 200, and 400 on the available Caelyx. Following physicochemical evaluations, animal experiments such as biodistribution, fluorescence microscopy, and pharmacokinetics were done. Results: In comparison with Caelyx, the 200L and 400L treatment arms were the most promising formulations. We showed that nanocarriers containing 40 times fewer GSH micelles than 2B3-101 significantly increased blood-brain barrier penetrance. Due to the expressed GSH receptors on tissues as an endogenous antioxidant, Doxorubicin will likely concentrate in the liver, spleen, heart, and lung in comparison with Caelyx, according to other tissue analyses. Conclusion: The post-insertion technique was found a successful approach with more pharmaceutical aspects for large-scale production. Moreover, further investigations are highly recommended to determine the efficacy of 5% post-inserted GSH targeted nanoliposomes versus 2B3-101 as a similar formulation with a different preparation method

Von Willebrand factor propeptide and pathophysiological mechanisms in European and Iranian patients with type 3 von Willebrand disease enrolled in the 3WINTERS-IPS study

Background Type 3 von Willebrand disease (VWD) is a severe bleeding disorder caused by the virtually complete absence of von Willebrand factor (VWF). Pathophysiological mechanisms of VWD like defective synthesis, secretion, and clearance of VWF have previously been evaluated using ratios of VWF propeptide (VWFpp) over VWF antigen (VWF:Ag) and factor (F)VIII coagulant activity (FVIII:C) over VWF:Ag. Objective To investigate whether the VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios may also be applied to understand the pathophysiological mechanism underlying type 3 VWD and whether VWFpp is associated with bleeding severity. Methods European and Iranian type 3 patients were enrolled in the 3WINTERS-IPS study. Plasma samples and buffy coats were collected and a bleeding assessment tool was administered at enrolment. VWF:Ag, VWFpp, FVIII:C, and genetic analyses were performed centrally, to confirm patients' diagnoses. VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios were compared among different variant classes using the Mann-Whitney test. Median differences with 95% confidence intervals (CI) were estimated using the Hodges-Lehmann method. VWFpp association with bleeding symptoms was assessed using Spearman's rank correlation. Results Homozygosity/compound heterozygosity for missense variants showed higher VWFpp level and VWFpp/VWF:Ag ratio than homozygosity/compound heterozygosity for null variants ([VWFpp median difference, 1.4 IU/dl; 95% CI, 0.2-2.7; P = .016]; [VWFpp/VWF:Ag median difference, 1.4; 95% CI, 0-4.2; P = .054]). FVIII:C/VWF:Ag ratio was similarly increased in both. VWFpp level did not correlate with the bleeding symptoms (r = .024; P = .778). Conclusions An increased VWFpp/VWF:Ag ratio is indicative of missense variants, whereas FVIII:C/VWF:Ag ratio does not discriminate missense from null alleles. The VWFpp level was not associated with the severity of bleeding phenotype.Peer reviewe

Bleeding symptoms in patients diagnosed as type 3 von Willebrand disease : Results from 3WINTERS-IPS, an international and collaborative cross-sectional study

Background Type 3 von Willebrand's disease (VWD) patients present markedly reduced levels of von Willebrand factor and factor VIII. Because of its rarity, the bleeding phenotype of type 3 VWD is poorly described, as compared to type 1 VWD. Aims To evaluate the frequency and the severity of bleeding symptoms across age and sex groups in type 3 patients and to compare these with those observed in type 1 VWD patients to investigate any possible clustering of bleeding symptoms within type 3 patients. Methods We compared the bleeding phenotype and computed the bleeding score (BS) using the MCMDM-1VWD bleeding questionnaire in patients enrolled in the 3WINTERS-IPS and MCMDM-1VWD studies. Results In 223 unrelated type 3 VWD patients, both the BS and the number of clinically relevant bleeding symptoms were increased in type 3 as compared to type 1 VWD patients (15 versus 6 and 5 versus 3). Intracranial bleeding, oral cavity, hemarthroses, and deep hematomas were at least five-fold over-represented in type 3 VWD. A more severe bleeding phenotype was evident in patients having von Willebrand factor antigen levels <20 IU/dL at diagnosis in the two merged cohorts. In type 3 patients, there was an apparent clustering of hemarthrosis with gastrointestinal bleeding and epistaxis, whereas bleeding after surgery or tooth extraction clusters with oral bleeding and menorrhagia. Conclusions In the largest cohort of type 3 VWD patients, we were able to describe a distinct clinical phenotype that is associated with the presence of a more severe hemostatic defect.Peer reviewe

Comparison of Single and Multiple Low-Level Laser Applications After Rapid Palatal Expansion on Bone Regeneration in Rats: Low-Level Laser Therapy After Palatal Expansion

Introduction: This study was performed to compare the effects of single and multiple irradiations of low-level laser therapy (LLLT) on bone regeneration in a mid-palatal suture following rapid palatal expansion (RPE).Methods: In this animal study, 40 male Wistar rats underwent RPE for 7 days and were divided into 4 groups including A: single LLLT on day 7, B: Multiple LLLT on days 7, 9, 11, 13 and 15, C: control (no LLLT), and D: sacrificed on day 7. Animals in group D were used to determine the amount of suture expansion. LLLT was done by a diode laser set at an 808 nm wavelength with a useful power output of 100 mW and duration of 0.1 ms. LLLT was applied to three points. After three weeks of retention, the rats were sacrificed and beheaded and the maxilla was evaluated by occlusal radiography, μ-CT, and histomorphometric analyses. A comparison of the mean measurements between the groups was performed using ANOVA and the Tukey post hoc test.Results: Based on occlusal radiography and μCT, bone density in group B was significantly higher than group A and group C (P &lt; 0.05). There was no significant difference in bone density between group A and group C (P &gt; 0.05). Mean suture width (MSW) in group B was significantly lesser than the control group (P = 0.027) while there was no significant difference between MSWnin groups A and B (P = 0.116) and groups A and C (P = 0.317).Conclusion: It may be concluded that multiple low-power laser irradiation improves bone regeneration after RPE while single irradiation does not have a positive effect

Correlation between blood lead concentration and iron deficiency in Iranian children

Background: Iron deficiency anaemia is the most common nutritional anaemia among children. Lead toxicity is a serious health threat, especially in developing countries due to environmental pollution. It was thus aimed to investigate correlation between blood lead concentration and iron deficiency in children of Mashhad, Iran. Materials and Methods: This cross sectional study was performed on children between 1 year and 10 years, in Imam Reza teaching hospital of Mashhad, Iran, in 2010. Indeed during complete blood count (CBC), we measured iron and total iron binding capacity (TIBC) by colorimetric methods, ferritin by radioimmune assay and blood lead concentration by atomic absorption method. Results were analysed by Statistical Package for Social Sciences (SPSS) (version 11.5), using statistical tests including independent sample t-test, Mann-Whitney U test, Spearman′s test and analysis of variance (ANOVA) and Pearson′s or Spearman′s correlation coefficient. P value ≤ 0.05 was considered as a significant level. Results: We studied 223 cases including 98 control children and 125 patients. All children had lead intoxication. Mean (±SD) blood lead concentration in the control group was 57.1 ± 25.3 (ranged 20-212) μg/dl and in the patient group was 57 ± 20.4 (ranged 10.9-159) μg/dl with no significant difference (P value = 0.713). We also did not find any correlation between blood lead concentration and haemoglobin, ferritin, iron, TIBC, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), white blood cells (WBC) and platelets. Conclusion: Based on these results, no correlation was found between blood lead concentration and iron deficiency in the children. Because all children had lead intoxication, further studies in highly polluted and a comparison with a low polluted area are necessary to make a general conclusion

Role of the Lewis and ABO Blood Group Antigens in Helicobacter pylori Infection

Background: Helicobacter pylori infection is a major risk factor for chronic gastritis and gastric cancer. Some findings show increased frequencies of these diseases in individuals with type O blood and in secretors (expressing Leb antigen), but other studies have not found any relationship between blood groups and this infection. Given that H. pylori infection and gastric cancer are common in Iran, the assessment of the pathogenesis of this infection in relation to these blood groups could be valuable. Methods: In a cross-sectional study, we determined the ABO and Lewis blood groups of participants using the tube method and evaluated the level of anti-H. pylori immunoglobulin G using an enzyme-linked immunosorbent assay. This study included 171 Iranian blood donors from Mashhad, Iran, during 2010. The significance of the differences in the frequencies of the Lewis and ABO phenotypes between individuals infected with and without H. Pylori infection were tested using the Chi-square test. A P-value < 0.05 was considered significant. Results: H. pylori infection was found in 76.6% of the study subjects (n = 131). The most common ABO blood group was O (33.9%), and the most common Lewis blood group was Le(a-b+) (54.7%). The frequencies of the ABO, Lewis, and secretion phenotypes were not significantly different between the infected and uninfected subjects. Conclusion: We did not find any significant relationship between the Lewis, ABO, and secretion phenotypes and H. pylori infection

The effect of 810-nm low-level laser therapy on pain caused by orthodontic elastomeric separators

The purpose of this study was to assess the effect of 810-nm (DMC Equipamentos, Sao Carlos, Brazil) continuous wave low-level laser therapy (LLLT) on the pain caused by orthodontic elastomeric separators. Thirty-seven orthodontic patients (12 male and 25 female, aged 11–32 years, mean age = 24.97 years) participated in the study, including 20 subjects aged 18 years or more, and 17 under 18 years of age. Four elastomeric separators (Dentarum, Springen, Germany) were placed for the first permanent molars (distal and mesial), either for maxillary (22 patients) or mandibular (15 patients) arches; one quadrant was randomly selected and used as a placebo group (received no laser irradiation). After separator placement for each quadrant, patients received 10 doses (2 J/cm2, 100 mW, 20 s) of laser irradiation on the buccal side (at the cervical third of the roots), for distal and mesial of the second premolars and first permanent molars, as well as distal of second permanent molars (five doses). The same procedure was repeated for the lingual or palatal side (five doses). After 24 h, patients returned to the clinic and received another 10 doses of laser irradiation on the same quadrant. Postseparation pain level recorded on a 10-cm visual analog scale for both jaws immediately (hour 0), and after 6, 24, 30 h, as well as on days 3, 4, 5, 6, and 7. Significant differences in the pain perception (PP) were found between the laser and placebo groups at 6, 24, 30 h, and day 3 of the experiment (P < 0.05). Friedman’s test of multiple comparisons revealed significant differences in the PP among various time intervals for laser (chi-square = 173.407, P = 0.000) and placebo (chi-square = 184.712, P = 0.000) groups. In both groups, pain was highest at 6 and 30 h after placing elastomeric separators. No gender differences were observed in both groups. More pain was recorded in the mandible (P < 0.05) at 24 (laser group) and 30 h (both groups) after starting the experiment. The PP was significantly higher (P < 0.05) for the group aged 18 years or more, only at days 3 [both groups] and 4 [laser group only] of the experiment. The 810-nm continuous wave LLLT significantly reduced the PP in the first 3 days after orthodontic separation. However, the mean postseparation PP in both groups was low and wide ranges of PP scores were observed

The Effect of An Angiogenic Cytokine on Orthodontically Induced Inflammatory Root Resorption

Objective Orthodontically induced inflammatory root resorption (OIIRR) is an undesirable sequel of tooth movement after sterile necrosis that takes place in periodontal ligament due to blockage of blood vessels following exertion of orthodontic force. This study sought to assess the effect of an angiogenic cytokine on OIIRR in rat model. Materials and Methods In this experimental animal study, 50 rats were randomly divided into 5 groups of 10 each: E10, E100 and E1000 receiving an injection of 10, 100 and 1000 ng of basic fibroblast growth factor (bFGF), respectively, positive control group (CP) receiving an orthodontic appliance and injection of phosphate buffered saline (PBS) and the negative control group (CN) receiving only the anesthetic agent. A nickel titanium coil spring was placed between the first molar and the incisor on the right side of maxilla. Twenty-one days later, the rats were sacrificed. Histopathological sections were made to assess the number and area of resorption lacunae, number of blood vessels, osteoclasts and Howship’s lacunae. Data were statistically analyzed using ANOVA and Tukey’s honest significant difference (HSD) test. Results Number of resorption lacunae and area of resorption lacunae in E1000 (0.97 ± 0.80 and 1. 27 ± 0.01×10-3, respectively) were significantly lower than in CP (4.17 ± 0.90 and 2.77 ± 0.01×10-3, respectively, P=0.000). Number of blood vessels, osteoclasts and Howship’s lacunae were significantly higher in E1000 compared to CP (P<0.05). Conclusion Tooth movement as the outcome of bone remodeling is concomitant with the formation of sterile necrosis in the periodontal ligament following blocked blood supply. Thus, bFGF can significantly decrease the risk of root resorption by providing more oxygen and angiogenesis