Histamine prevents radiation-induced mesenchymal changes in breast cancer cells.

Radiotherapy is a prime option for treatment of solid tumors including breast cancer though side effects are usually present. Experimental evidence shows an increase in invasiveness of several neoplastic cell types through conventional tumor irradiation. The induction of epithelial to mesenchymal transition is proposed as an underlying cause of metastasis triggered by gamma irradiation. Experiments were conducted to investigate the role of histamine on the ionizing radiation-induced epithelial to mesenchymal transition events in breast cancer cells with different invasive phenotype. We also evaluated the potential involvement of Src phosphorylation in the migratory capability of irradiated cells upon histamine treatment. MCF-7 and MDA-MB-231 mammary tumor cells were exposed to a single dose of 2Gy of gamma radiation and five days after irradiation mesenchymal-like phenotypic changes were observed by optical microscope. The expression and subcellular localization of E-cadherin, ß-catenin, vimentin and Slug were determined by immunoblot and indirect immunofluorescence. There was a decrease in the epithelial marker E-cadherin expression and an increase in the mesenchymal marker vimentin after irradiation. E-cadherin and ß-catenin were mainly localized in cytoplasm. Slug positive nuclei, matrix metalloproteinase-2 activity and cell migration and invasion were significantly increased. In addition, a significant enhancement in Src phosphorylation/activation could be determined by immunoblot in irradiated cells. MCF-7 and MDA-MB-231 cells also received 1 or 20µM histamine during 24h previous to be irradiated. Notably, pre-treatment of breast cancer cells with 20µM histamine prevented the mesenchymal changes induced by ionizing radiation and also reduced the migratory behavior of irradiated cells decreasing phospho-Src levels. Collectively, our results suggest that histamine may block events related to epithelial to mesenchymal transition in irradiated mammary cancer cells and open a perspective for the potential use of histamine to improve radiotherapy efficacy.

H2 antihistamines: May be useful for combination therapies in cancer?

Cancer morbimortality is still a great concern despite advances in research and therapies. Histamine and its receptors' ligands can modulate different biological responses according to the cell type and the receptor subtype involved. Besides the wide variety of histamine functions in normal tissues, diverse roles in the acquisition of hallmarks of cancer such as sustained proliferative signaling, resistance to cell death, angiogenesis, metastasis, altered immunity and modified microenvironment have been described. This review summarizes the present knowledge of the various roles of histamine H2 receptor (H2R) ligands in neoplasias. A bioinformatic analysis of human tumors showed dissimilar results in the expression of the H2R gene according to tumor type when comparing malignant versus normal tissues. As well, the relationship between patients' survival parameters and H2R gene expression levels also varied, signaling important divergences in the role of H2R in neoplastic progression in different cancer types. Revised experimental evidence showed multiple effects of H2R antihistamines on several of the cited hallmarks of cancer. Interventional and retrospective clinical studies evaluated different H2R antihistamines in cancer patients with two main adjuvant uses: improving antitumor efficacy (which includes regulation of immune response) and preventing toxic adverse effects produced by chemo or radiotherapy. While there is a long path to go, research on H2R antihistamines may provide new opportunities for developing more refined combination therapeutic strategies for certain cancer types to improve patients' survival and health-related quality of life.

"Effect of Heat Generated by Endodontic Obturation Techniques on Bond Strength of Bioceramic Sealers to Dentine".

INTRODUCTION: Gutta-percha combined with an endodontic sealer remains the most widely used obturation technique. Bioceramic sealers (BS) were developed for root canal obturation in combination with gutta-percha cones using the cold single-cone technique. Few studies have assessed the effect of thermal treatment on the performance of BS. The present study evaluated the effect of heat on BS adhesion to root dentine in the apical third of the root canal of extracted human lower premolars. MATERIALS AND METHODS: Three BS combined with a hydraulic condensation technique, a warm vertical compaction technique, and a carrier-based technique were evaluated. Sixty three lower premolars were prepared following the same surgical protocol to standardize root canal shape at the level of the apex, randomly assigned to one of nine groups, and obturated accordingly. One millimeter-thick sections were subjected to a push-out test using a universal testing machine and classified according to mode of failure. Two-way ANOVA was applied using SPSS software (IBM Corp). RESULTS: No significant differences in maximum load or failure mode were observed among BS, techniques, or when considering the interaction between sealers and techniques. CONCLUSIONS: The heat generated by the obturation techniques used here did not affect BS adhesion to the dentinal wall.

Effect of Dentin Conditioning with EDTA and Diode Lasers on Expression of Odontoblast-like Cell Markers of Dental Pulp Stem Cells.

Regenerative endodontic procedures rely on the delivery of mesenchymal stem cells into the root canal and on the effect of local growth factors from the dentin and blood clot. The aim of this study was to assess the effect of dentin conditioning with ethylenediamine tetraacetic acid (EDTA) and diode lasers with different wavelengths (808 nm and 980 nm) on the expression of odontoblast-like cell markers. Forty dentin cylinders were divided into four groups according to the irrigation protocol: EDTA, EDTA + 808 nm diode laser, EDTA + 980 nm diode laser, and phosphate-buffered saline as the control group. Dental pulp stem cells were seeded into the previously conditioned cylinders and incubated for 14 days. The quantitative real-time polymerase chain reaction was used to evaluate the expression of dentin sialophosphoprotein (DSPP), dentin morphoprotein-1 (DMP-1), and transforming growth factor-beta 1 (TGF-ß1). Data analysis was performed using the Kruskal-Wallis test. The activation of EDTA with 980 nm and 808 nm diode lasers resulted in lower DSPP and DMP-1 expression than that for EDTA alone (p < 0.05 and p < 0.01, respectively). The expression of TGF was similar among all groups. The highest level of expression of odontoblast-like differentiation markers was observed with EDTA alone. However, the use of an 808 nm diode laser during EDTA irrigation reduced the expression of odontoblastic differentiation markers.

Radiotherapy for Brain Metastases Near the End of Life: Characterizing Patients and Tumor Features.

PURPOSE: Patients with brain metastases are often referred for brain radiotherapy (BrRT) when exclusive palliative management would be more appropriate. To assess the indication of BrRT during end-of-life (EOL) care and evaluate the characteristics of the patients who underwent the treatment. METHODS: This retrospective study comprised patients from four independent oncology centers who had undergone BrRT for metastases. The variables included were Karnofsky performance status (KPS), primary tumor site, metastatic status, neurologic symptomatic status, the number and size of metastases, posterior fossa or meningeal involvement, type of BrRT, having undergone brain metastasectomy, and the availability of systemic therapies after BrRT. Patients were allocated into three subgroups with ≤30, 31-60, and 61-90 days of survival, and a control group of patients who survived >90 days. RESULTS: A total of 546 patients were included in the study. A KPS of <70 (P = .021), the number of brain metastases (P = .001), the lack of brain metastasectomy (P = .006), and the lack of systemic therapies after BrRT (P = .047) were significantly associated with the EOL subgroups. Multivariate analysis showed that a KPS of <70 (P < .001), the lack of brain metastasectomy (P = .015), and the lack of systemic therapies after BrRT (P = .027) were significantly associated with worse survival. In all, 241 (44.1%) patients died within 90 days-120 (22.0%) within 30 days, 75 (13.7%) within 31-60 days, and 46 (8.4%) within 61-90 days of BrRT. Patients with colorectal cancer were significantly more likely to die within 90 days of BrRT than >90 days. CONCLUSION: Considering patients' performance status and whether they are candidates for brain metastasectomy or systemic therapies after BrRT is critical to improving BrRT benefits in scenarios of EOL.

Co-design of a Community-based Rehabilitation Program to Decrease Musculoskeletal Disabilities in a Mayan-Yucateco Municipality.

BACKGROUND: Chronic musculoskeletal (MSK) diseases are an important cause of disability in the Mayan community of Chankom in Yucatán, Mexico. OBJECTIVE: To understand a community-based participatory research (CBPR) strategy implemented in Chankom to design a community-based rehabilitation (CBR) program for people living with MSK diseases. METHODS: Qualitative descriptive thematic analysis from an ethnographic work conducted in Chankom, during the implementation of a CBPR strategy from 2014 to 2017. RESULTS: Four main themes describe the main processes that formed our CBPR strategy: 1) forming and maintaining an alliance between academic and community members, 2) prioritizing community needs, 3) integrating local and global knowledge and 4) shared-decision-making. This CBPR strategy allowed the design of a CBR program formed by six main interventions: 1) health services coordination, 2) personal support, 3) community venous blood sampling services, 4) community specialized services, 5) health promotion, and 6) health transportation services. CONCLUSIONS: Co-designing a CBR program for people living with chronic MSK diseases in Chankom was possible through an extensive community engagement work structured around four main processes, including the essential principles of CBPR. The designed CBR program includes culturally sensitive interventions aimed at improving the quality, availability, accessibility, and acceptability of health care services. Moreover, the program mainly addressed the "health" component of the World Health Organization-CBR matrix, suggesting a need for a new CBPR cycle after it is implemented and evaluated in the future.

Genomic history of coastal societies from eastern South America.

Sambaqui (shellmound) societies are among the most intriguing archaeological phenomena in pre-colonial South America, extending from approximately 8,000 to 1,000 years before present (yr BP) across 3,000 km on the Atlantic coast. However, little is known about their connection to early Holocene hunter-gatherers, how this may have contributed to different historical pathways and the processes through which late Holocene ceramists came to rule the coast shortly before European contact. To contribute to our understanding of the population history of indigenous societies on the eastern coast of South America, we produced genome-wide data from 34 ancient individuals as early as 10,000 yr BP from four different regions in Brazil. Early Holocene hunter-gatherers were found to lack shared genetic drift among themselves and with later populations from eastern South America, suggesting that they derived from a common radiation and did not contribute substantially to later coastal groups. Our analyses show genetic heterogeneity among contemporaneous Sambaqui groups from the southeastern and southern Brazilian coast, contrary to the similarity expressed in the archaeological record. The complex history of intercultural contact between inland horticulturists and coastal populations becomes genetically evident during the final horizon of Sambaqui societies, from around 2,200 yr BP, corroborating evidence of cultural change.

PANC-1 cells proliferative response to ionizing radiation is related to GSK-3ß phosphorylation.

Radiotherapy may be used to treat pancreatic cancer and relieve pain. We have previously reported that histamine modulates pancreatic adenocarcinoma PANC-1 cell proliferation. This work was aimed to evaluate whether histamine improves radiosensitivity of PANC-1 cells in relation to phosphorylation/inhibition of glycogen synthase kinase-3ß (GSK-3ß). Immediately after γ irradiation, intracellular hydrogen peroxide was markedly decreased together with a rapid increase in catalase activity. Although histamine diminished catalase activity in nonirradiated cells, it only partially hindered the increase observed in irradiated cells and could not modify radiosensitivity. In control cells, a high expression of total and a very low expression of phosphorylated/inactive GSK-3ß were found. An increment in reactive oxygen species levels produced an augmentation in GSK-3ß phosphorylation and suppressed cell proliferation. In both control and histamine-treated irradiated cells, the rise in catalase activity lowered reactive oxygen species levels and only a small increase in phosphorylated GSK-3ß was detected. Alternatively, 3-aminotriazole, an irreversible inhibitor of catalase, reduced the survival fraction in irradiated control cells along with an increment in phosphorylated GSK-3ß. These results suggest that upon irradiation, early catalase activation may be responsible for keeping GSK-3ß active conceding cells a survival advantage toward cytotoxic effects of ionizing radiation.

Non-tumorigenic epithelial breast cells and ionizing radiation cooperate in the enhancement of mesenchymal traits in tumorigenic breast cancer cells.

AIMS: Radioresistance and recurrences are crucial hindrances in cancer radiotherapy. Fractionated irradiation can elicit a mesenchymal phenotype in irradiated surviving cells and a deep connection exists between epithelial mesenchymal transition, radioresistance, and metastasis. The aim of this study was to analyze the effect of the secretoma of irradiated non-tumorigenic mammary epithelial cells on surviving irradiated breast tumor cells regarding the gain of mesenchymal traits and migratory ability. MAIN METHODS: MDA-MB-231 and MCF-7 breast cancer cells, irradiated or not, were incubated with conditioned media from MCF-10A non-tumorigenic epithelial breast cells, irradiated or not. After five days, we evaluated the expression and localization of epithelial and mesenchymal markers (by western blot and indirect immunofluorescence), cell migration (using transwells) and metalloproteinases activity (by zymography). We also assessed TGF-ß1 content in conditioned media by immunoblot, and the effect of A83-01 (a selective inhibitor of TGF-ß receptor I) and PP2 (a Src-family tyrosine kinase inhibitor) on nuclear Slug and cell migration. KEY FINDINGS: Conditioned media from MCF-10A cells caused phenotypic changes in breast tumor cells with attainment or enhancement of mesenchymal traits mediated at least in part by the activation of the TGF-ß type I receptor and a signaling pathway involving Src activation/phosphorylation. The effects were more pronounced mostly in irradiated tumor cells treated with conditioned media from irradiated MCF-10A. SIGNIFICANCE: Our results suggest that non-tumorigenic epithelial mammary cells included in the irradiation field could affect the response to irradiation of post-surgery residual cancer cells enhancing EMT progression and thus modifying radiotherapy efficacy.

Morphometric affinities and direct radiocarbon dating of the Toca dos Coqueiros' skull (Serra da Capivara, Brazil).

The biological variation of the earliest skeletons of South America has been intensely debated for the last two centuries. One of the major research constraints has been the limited number of available samples dating to the early Holocene. We here present the first direct radiocarbon-date for the early Holocene human skeleton from Toca dos Coqueiros (Serra da Capivara, Brazil), also known as "Zuzu" (8640 ± 30 BP; 9526-9681 cal years BP). We performed craniometric analyses using exclusively samples from Brazil, to revisit the sex of the skeleton, and to discuss the evolutionary processes involved in the occupation of the continent. The sex of the individual was estimated as a female when compared to late and early Holocene individuals, but as a male when compared only to the early Holocene series. We also found that Zuzu presents the strongest differences with the late Holocene Guajajara individuals, located nearby, and the strongest similarities with the early Holocene series from Lagoa Santa, attesting for solid biological affinities among early Holocene individuals from Brazil, as well as a moderate level of morphological variation among them. This suggests that the early individuals were part of the same heterogeneous lineage, possibly a different one from which late Holocene populations diverged.

Amerindian mtDNA haplogroups and celiac disease risk HLA haplotypes in mixed-blood Latin American patients.

BACKGROUND AND OBJECTIVE: Risk haplotypes have been described in celiac disease (CD), but the influence of native genes on CD in Hispanic Americans is unknown. The aim of the study was to measure the frequency of Amerindian mitochondrial DNA (mtDNA) haplogroups (inherited by the maternal line) in mixed-blood patients with CD from Chile, Argentina, and Uruguay, and to assess the relation between these and human leukocyte antigen (HLA) alleles and haplotypes and clinical presentations. PATIENTS AND METHODS: Clinical history, histological data, and genetic studies were conducted following 2 protocols: a case-control study of 72 Chilean patients with CD and controls, and an assessment of 43 (additional) samples of celiac patients from Chile, 96 from Argentina, and 57 from Uruguay, compared with the mtDNA frequency in the corresponding country. HLA typing was performed by a commercial kit, and mtDNA was determined by means of polymerase chain reaction and restriction fragment length polymorphisms analysis. RESULTS: A total of 73.6% of cases had typical presentations. The most frequent HLA alleles were HLA-DQB*201 and 202. No-DQ2/DQ8 HLA haplotypes were found in 7% of cases. mtDNA frequencies for typical Amerindian haplogroups were found in 71% of cases and 64% of controls (P χ2 = 0.016); in the comparative analysis, mtDNA distribution was not different from the figures reported for the respective general country population. No relation was found between haplotypes or haplogroups and clinical presentations. CONCLUSIONS: mtDNA haplogroups A/B/C/D were frequently found in celiac patients and controls, but no relations appeared between haplogroups, haplotypes, and clinical presentations.

The secretome of non-tumorigenic mammary cells MCF-10A elicits DNA damage in MCF-7 and MDA-MB-231 breast cancer cells.

Radiotherapy is used in breast cancer to destroy tumor cells lingering after surgery. It is accepted that lethal effects of ionizing radiation occur as a result of damage to DNA in irradiated (IR) cells. However, response mechanisms may promote cell survival with efficient DNA repair or genomic alterations. Chromosomal aberrations are frequent in surviving cells and may enhance chromosomal instability (CIN) which is associated with increased risk of recurrence and metastasis. Intercellular communication can affect the response in IR cells and cause damage in non-irradiated (N-IR) cells. We evaluated the effect of the secretome of non-tumorigenic mammary cells (MCF-10A) on proliferation and DNA damage in breast cancer cells (MCF-7 and MDA-MB-231). Results showed that conditioned media from IR and N-IR MCF-10A cells produced cycles of DNA double-strand breaks in N-IR and IR tumor cells leaving them with residual damage. CIN markers (micronuclei, nucleoplasmic bridges, nuclear buds) were also increased in IR and N-IR tumor cells, being the effect of conditioned media from IR MCF-10A greater in many cases. The inhibition of phosphorylation/activation of Src kinase in cancer cells hindered CIN markers' increment. Besides, clonogenic survival of tumor cells was differentially modulated by conditioned media from MCF-10A: decreased in MCF-7 and enhanced in MDA-MB-231 cells. These results signal the relevance of tumor-host interaction in tumor behavior and the response to radiotherapy.

Root dentine thickness in C-shaped lower second molars after instrumentation: A CBCT and micro-CT study.

Stripping perforation is a possible complication in instrumentation of C-shaped canals. This study evaluated the minimum thickness of the root canal wall in C-shaped teeth after instrumentation. Twelve extracted C-shaped mandibular second molars (four teeth of type I, II and III each) were examined by CBCT (voxel size 90 µm) before and after instrumentation with WOG primary file. Micro-CT scans (voxel size 30 µm) were obtained after instrumentation. Percentage of canal wall area touched by the file and minimum thickness of dentine were measured and compared between CBCT and micro-CT. In type I C-shape canals, less than 10% of the canal wall area was touched by the instrument. In ten teeth, the shortest distance to root surface was from the instrumented area; no perforations occurred. CBCT and micro-CT measurements were in good agreement in ten cases; in two teeth, micro-CT revealed considerably shorter distance to root surface. The two shortest distances were 0.27 and 0.41 mm.

Effects of Endodontic Infections on the Maxillary Sinus: A Case Series of Treatment Outcome.

This article shows the follow-up of several cases of maxillary sinusitis of dental (usually endodontic) origin, with different manifestations, diagnostic challenges, and outcomes.Cases from 14 patients from 3 countries and treated by 7 different endodontists are presented, all of them with inflammatory sinus changes represented by mucositis, osteoperiostitis, and/or partial/full obstruction. All cases showed dental and/or sinus signs/symptoms that resolved after dental management. In 13 cases, the sinus condition had an endodontic origin, 4 of them concurrently with periodontal involvement. In 1 case, sinusitis was caused by trauma to the face. All cases but 1 had a satisfactory response of the periradicular tissues and maxillary sinus to treatment that consisted of root canal therapy, root amputation, extraction, or trauma management.The successful management of most cases reported in this article emphasizes the importance of endodontics as a specialty engaged in saving teeth and promoting health not only in the oral cavity but also in other areas that may be affected by infections of endodontic origin, including the maxillary sinus.

Histamine H4 receptor agonists induce epithelial-mesenchymal transition events and enhance mammosphere formation via Src and TGF-ß signaling in breast cancer cells.

Epithelial-mesenchymal transition (EMT) contributes to cell invasion and metastasis during the progression of epithelial cancers. Though preclinical evidence suggests a role for histamine H4 receptor (H4R) in breast cancer growth, its function in the EMT is less known. In this study we proposed to investigate the effects of H4R ligands on EMT and mammosphere formation as a surrogate assay for cancer stem cells in breast cancer cells with different invasive phenotype. We also investigated the participation of Src and TGF-ß signaling in these events. Breast cancer cells were treated with the H4R agonists Clobenpropit, VUF8430 and JNJ28610244 and the H4R antagonist JNJ7777120. Immunodetection studies showed cytoplasmic E-cadherin, cytoplasmic and nuclear beta-catenin, nuclear Slug and an increase in vimentin and α-smooth muscle actin expression. There was also an enhancement in cell migration and invasion assessed by transwell units. All these effects were prevented by JNJ7777120. Moreover, H4R agonists induced an increase in phospho-Src levels detected by Western blot. Results revealed the involvement of phospho-Src in EMT events. Upon treatment with H4R agonists there was an increase in phospho-ERK1/2 and TGF-ß1 levels by Western blot, in Smad2/3 positive nuclei by indirect immunofluorescence, and in tumor spheres formation by the mammosphere assay. Notably, the selective TGF-ß1 kinase/activin receptor-like kinase inhibitor A83-01 blocked these effects. Moreover, cells derived from mammospheres exhibited higher Slug expression and enhanced migratory behavior. Collectively, findings support the interaction between H4R and TGF-ß receptor signaling in the enhancement of EMT features and mammosphere formation and point out intracellular TGF-ß1 as a potential mediator of these events.

Expression of estrogen receptor α variants and c-Fos in rat mammary gland and tumors.

Breast cancer is currently the leading cause of cancer death among women worldwide. AP-1 (c-Fos/c-Jun) is associated with proliferation and survival, while cytoplasmic c-Fos activates phospholipid synthesis in cells induced to differentiate or grow. Estrogen receptor α 46 (ERα46) is a splice variant of full-length ERα66 and it is known that it has an inhibitory role in cancer cell growth. We investigated c-Fos localization, its relationship to AP-1, the non genomic pathway of phospho-Tyr537-ERα66, as well as ERα46 and ERα66 isoforms in rat mammary gland development and carcinogenic transformation, and in mammary tumors. Female rats were injected: a) saline solution (Control mammary gland, CMG) or b) N-Nitroso-N-methyl urea (NMU), and samples were taken at 60, 90, 120 and 150 days of life. In addition, we analyzed hormone-dependent (HD) and independent (HI) tumors in ovariectomized rats, and intact tumors (IT) in non-ovariectomized ones. Our results show that, in CMG, nuclear c-Fos and proliferation decreased with age, AP-1 content was low, and nuclear ERα46/ERα66 ratio was higher than 1. In NMU, nuclear c-Fos and proliferation increased with carcinogenic transformation, AP-1 content was high, and nuclear ERα46/ERα66 was below 1. As tumor grade increased, proliferation, nuclear c-Fos and AP-1 expression were negatively associated to nuclear ERα46/ERα66 in IT. In HD, nuclear ERα46/ERα66, nuclear c-Fos expression, AP-1 levels and proliferation were lower than in HI, whose growth is estrogen-independent. Phospho-Tyr537-ERα66 content and ERK1/2 activation were associated with AP-1 levels and cell proliferation. Collectively, our findings support the notion that variant detection and ERα46/ERα66 ratio could shed light on the role of ERα isoforms in mammary gland transformation and the behavior of ERα positive mammary tumors.

Ancient Parasite Analysis and Zoonotic Potential of Spirometra sp. in Two Related Sites from Pernambuco, Brazil.

Pathoecology studies the environmental and cultural factors that contribute to the maintenance of infections or diseases in populations. Concerning parasites, it requires the evaluation of these factors based on the presence and life cycle of these organisms. For this reason, it is possible to apply this concept in the context of ancient populations in order to understand the parasite-host dynamic or even the health consequences faced by the members of the populations. This study aimed to apply the pathoecology concept in Pedra do Tubarão and Cemitério do Caboclo archaeological sites. Six coprolite samples were analyzed and 1 was positive for Spirometra sp. eggs. Spirometra is a cestode that has copepods as the first intermediate host; amphibians, reptiles, birds, and mammals as the second intermediate hosts; and felines and canines as definitive hosts. Humans can be infected by ingesting the first or second intermediate hosts and can develop sparganosis, which can cause health consequences depending on the location of the spargana. The presence of this parasite, of a water fount near the site, where the first intermediate host can live, and the findings of the bones of some of the second intermediate hosts in these sites, suggesting dietary purposes, indicate that this infection was probably present in this population.

Colchicine-Induced Rhabdomyolysis: Clinical, Biochemical, and Neurophysiological Features and Review of the Literature.

We report the case of a 46-years-old man with long-term asymptomatic hyperuricemia who started taking colchicine (0.5 mg/day) and allopurinol (100 mg/d) for normalization of biochemical values. After the third week of starting treatment, acute weakness was present; and by the fifth week, profound weakness in lower extremities and tenderness and cramps on thighs and calves with inability to climb stairs were also observed. Biochemical evaluation showed elevated muscle enzymes (creatinine kinase [CK] raised to five-folds its normal value) and electromyographic features were consistent with myopathy (at rest, fibrillations, positive sharp waves, high-frequency myotonic discharges; motor unit action potentials [MUAPs] of small amplitude, small duration, increased polyphasic Index and occasional satellite potentials; at maximal effort, interferential recruitment pattern with reduced amplitudes were observed). Normal motor and sensitive nerve conduction studies and normal late F-responses and H-reflex discarded neuropathy. Rapid improvement in muscle strength and prompt resolution of abnormal elevated muscle enzymes was observed after withdrawal of both medications. Colchicine is associated with some cases of myotoxicity but very small cases of colchicine-induced rhabdomyolysis are reported on the literature. Colchicine-induced rhabdomyolysis is related to the concomitant use of drugs (statins, steroids, erythromycin, and cyclosporine), renal, and/or hepatic impairment. To the best of our knowledge, this is an uncommon presentation of a case of colchicine-induced rhabdomyolysis reported in a patient without renal or hepatic dysfunction. Therefore, patients receiving colchicine even in the absence of renal insufficiency should be monitored for the development of myopathy and more rarely to rhabdomyolysis.

Continued root maturation despite persistent apical periodontitis of immature permanent teeth after failed regenerative endodontic therapy.

Three immature permanent teeth with pulp necrosis and apical periodontitis were treated with regenerative endodontic therapy (RET), which included root canal disinfection with sodium hypochlorite irrigation, intra-canal medication with calcium hydroxide paste, 17% EDTA rinse, induction of periapical bleeding into the canal, collagen matrix and MTA coronal seal, and composite resin restoration of access cavities. After different periods of follow-up, it was observed that continued root maturation, especially apical closure occurred despite persistent apical periodontitis of immature permanent teeth after failed RET. This finding is of interest as the secondary goal of further root maturation occurred despite failure of the primary goal of elimination of clinical symptom/sign and periapical inflammation. The possible biological mechanisms that could allow for further root maturation to occur in spite of persistent root canal infection of immature permanent teeth are discussed. Based on these observations, the biology of wound healing of immature permanent teeth after injury is not fully understood and should be further investigated. This case report demonstrates that whilst further root maturation is considered a successful outcome for teeth treated with RET, the primary objective must be the resolution of the signs and symptoms of apical periodontitis.