Expression of Musashi-1 Increases in Bone Healing.

Musashi-1 (MSI1) is an RNA-binding protein that regulates progenitor cells in adult and developing organisms to maintain self-renewal capacities. The role of musashi-1 in the bone healing environment and its relation with other osteogenic factors is unknown. In the current study, we analyze the expression of MSI1 in an experimental model of rat femoral bone fractures. We also analyze the relation between MSI1 expression and the expression of two osteogenic markers: periostin (POSTN) and runt-related transcription factor 2 (RUNX2). We use histological, immunohistochemical, and qPCR techniques to evaluate bone healing and the expression of MSI1, POSTN, and RUNX2 over time (4, 7, and 14 days). We compare our findings with non-fractured controls. We find that in bone calluses, the number of cells expressing MSI1 and RUNX2 increase over time and the intensity of POSTN expression decreases over time. Within bone calluses, we find the presence of MSI1 expression in mesenchymal stromal cells, osteoblasts, and osteocytes but not in hypertrophic chondrocytes. After 14 days, the expression of MSI1, POSTN, and RUNX2 was significantly correlated. Thus, we conclude that musashi-1 potentially serves in the osteogenic differentiation of mesenchymal stromal cells and bone healing. Therefore, further studies are needed to determine the possibility of musashi-1's role as a clinical biomarker of bone healing and therapeutic agent for bone regeneration.

Effects of Ischemic Preconditioning and C1 Esterase Inhibitor Administration following Ischemia-Reperfusion Injury in a Rat Skin Flap Model.

BACKGROUND: Ischemia-reperfusion (I/R) injury is a serious condition that can affect the success rate of microsurgical reconstructions of ischemic amputated limbs and complex tissue defects requiring free tissue transfers. The purpose of this study was to evaluate the effects of ischemic preconditioning (IPC) and C1 esterase inhibitor (C1-Inh) intravenous administration following I/R injury in a rat skin flap model. METHODS: Superficial caudal epigastric skin flaps (3 cm × 7 cm) were performed on 50 Wistar rats that were randomly divided into five groups. Ischemia was not induced in the control group. All other flaps underwent 8 hours of ischemia prior to revascularization: I/R control group (8-hour ischemia), IPC group (preconditioning protocol + 8-hour ischemia), C1-Inh group (8-hour ischemia + C1-Inh), and IPC + C1-Inh group (preconditioning protocol + 8-hour ischemia + C1-Inh). Survival areas were macroscopically assessed after 1 week of surgery, and histopathological and biochemical evaluations were also measured. RESULTS: There were no significant differences in flap survival between the treatment groups that were suffering 8 hours of ischemia and the control group. A significant increase in neovascularization and lower edema formation were observed in the IPC group compared with that in the I/R group. Biochemical parameters did not show any significant differences. CONCLUSION: Intravenous administration of C1-Inh did not significantly modulate I/R-related damage in this experimental model, but further research is needed. On the other hand, IPC reduces tissue damage and improves neovascularization, confirming its potential protective effects in skin flaps following I/R injury.

Increased Expression of Musashi-1 Evidences Mesenchymal Repair in Maxillary Sinus Floor Elevation.

This study aimed to analyze the expression of Musashi-1 (MSI1) in maxillary native bone and grafted bone after maxillary sinus floor elevation. To do so, fifty-seven bone biopsies from 45 participants were studied. Eighteen samples were collected from native bone while 39 were obtained 6 months after maxillary sinus grafting procedures. Musashi-1 was analyzed by immunohistochemistry and RT-PCR. MSI1 was detected in osteoblasts and osteocytes in 97.4% (38/39) of grafted areas. In native bone, MSI1 was detected in only 66.6% (12/18) of the biopsies, mainly in osteocytes. Detection of MSI1 was significantly higher in osteoprogenitor mesenchymal cells of grafted biopsies (p < 0.001) but minor in smooth muscle and endothelial cells; no expression was detected in adipocytes. The mesenchymal cells of the non-mineralized tissue of native bone showed very low nuclear expression of MSI1, in comparison to fusiform cells in grafted areas (0.28(0.13) vs. 2.10(0.14), respectively; p < 0.001). Additionally, the detection of MSI1 mRNA was significantly higher in biopsies from grafted areas than those from native bone (1.00(0.51) vs. 60.34(35.2), respectively; p = 0.029). Thus, our results regardig the significantly higher detection of Musashi-1 in grafted sites than in native bone reflects its importance in the remodeling/repair events that occur after maxillary sinus floor elevation in humans.

Endometrial Changes in Surgical Specimens of Perimenopausal Patients Treated With Ulipristal Acetate for Uterine Leiomyomas.

Ulipristal acetate (UPA) is used to treat leiomyomas, and its effect on the endometrium has been studied in biopsy material. Reversible histologic modifications were found, named progesterone receptor modulators-associated endometrial changes (PAEC). However, hysterectomies from patients treated with UPA have not been analyzed. For the first time, we examined surgical specimens from 100 leiomyoma-treated patients for UPA-related endometrial changes. We analyzed the distribution of lesions, involution after treatment, and the relationship between type and extent of lesions and dosage. Clinically, 72 patients were treated with 1 cycle of UPA; 23 patients with 2 cycles, and 5 with 3 cycles. A total of 66 patients underwent surgery in the first 4 wk after treatment, 24 were operated between 5 and 12 wk after discontinuation of UPA, and 10 after more than 12 wk after the last cycle, up to a maximum of 32 wk. Histologically normal endometria were found in 41 cases and PAEC in 59 cases. PAEC consisted of irregular, cystic glands showing a flattened secretory-like epithelium with vacuolation, coexisting mitoses and apoptosis, and were found focally within cyclic endometria in 51 cases. Only in 8 cases did diffuse PAEC involve the whole endometrium, transforming it into a thick spongy cushion. PAEC also occurred in adenomyosis. There was no relationship between dosage and type and extent of lesions. Diffuse PAEC, which usually presents differential diagnoses with hyperplasia, occurred in only 8 cases, being only present during the first 4 wk after discontinuation of treatment and was independent of the number of cycles administered.

Ghrelin and adipose-derived mesenchymal stromal cells improve nerve regeneration in a rat model of epsilon-caprolactone conduit reconstruction.

OBJECTIVE: Attempts have been made to improve nerve conduits in peripheral nerve reconstruction. We investigated the potential therapeutic effect of adipose-derived mesenchymal cells (ASCs) and ghrelin (GHR), a neuropeptide with neuroprotective, trophic, and developmental regulatory actions, on peripheral nerve regeneration in a model of severe nerve injury repaired with nerve conduits. MATERIAL AND METHODS: The right sciatic nerves of 24 male Wistar rats were 10-mm transected unilaterally and repaired with Dl-lactic-ε-caprolactone conduits. Rats were then treated locally with saline, ASCs, or GHR. At 12 weeks post-surgery, we assessed limb function by measuring ankle stance angle and percentage muscle mass reduction and evaluated the histopathology, immunohistochemistry, ultrastructure, and morphometry of myelinated fibers. MAIN RESULTS: Rats receiving GHR or ASCs showed no significant increased functional recovery in ankle stance angle (p=0.372) but a higher nerve area (p=0.015), myelin area (p=0.046) and number of myelinated fibers (p=0.012) in the middle and distal segments of operated sciatic nerves in comparison to saline-treated control animals. CONCLUSION: These results suggest that utilization of ghrelin or ASCs may improve nerve regeneration using Dl-lactic-ε-caprolactone conduits.

Osteoarticular Expression of Musashi-1 in an Experimental Model of Arthritis.

BACKGROUND: Collagen-induced arthritis (CIA), a murine experimental disease model induced by immunization with type II collagen (CII), is used to evaluate novel therapeutic strategies for rheumatoid arthritis. Adult stem cell marker Musashi-1 (Msi1) plays an important role in regulating the maintenance and differentiation of stem/precursor cells. The objectives of this investigation were to perform a morphological study of the experimental CIA model, evaluate the effect of TNFα-blocker (etanercept) treatment, and determine the immunohistochemical expression of Msi1 protein. METHODS: CIA was induced in 50 male DBA1/J mice for analyses of tissue and serum cytokine; clinical and morphological lesions in limbs; and immunohistochemical expression of Msi1. RESULTS: Clinically, TNFα-blocker treatment attenuated CIA on day 32 after immunization (P < 0.001). Msi1 protein expression was significantly higher in joints damaged by CIA than in those with no lesions (P < 0.0001) and was related to the severity of the lesions (Spearman's rho = 0.775, P = 0.0001). CONCLUSIONS: Treatment with etanercept attenuates osteoarticular lesions in the murine CIA model. Osteoarticular expression of Msi1 protein is increased in joints with CIA-induced lesion and absent in nonlesioned joints, suggesting that this protein is expressed when the lesion is produced in order to favor tissue repair.

Ovarian Small Cell Carcinoma of Pulmonary Type Arising in Mature Cystic Teratomas With Metastases to the Contralateral Ovary.

A bilateral small cell ovarian carcinoma pulmonary-type (SCCOPT), arising in bilateral mature cystic teratomas (MCTs) presented as stage IIIB in a 37-year-old woman. Microscopically, tumor nests were related to the dermoid protuberance and expressed pancytokeratin, EMA, CD56, chromogranin A, NSE, synaptophysin, and SOX2. SALL4 was also focally positive. CDX2, TTF1, PAX8, CK7, CK20, and several neuroendocrine gut hormones were negative. Serum NSE was elevated. This case represents a SCCOPT arising in an MCT in the right ovary with metastasis to the left one also containing a synchronous MCT. Surface implants and lymphovascular invasion suggested metastasis from the right ovarian SCCOPT and excluded a metastatic origin from usual locations of small cell carcinoma (SCC). SCCOPT is morphologically identical to SCC elsewhere, even sharing NSE serum elevation. Although the tumor was closely related to teratomatous mature tissues, a complex immunohistochemical panel failed to provide a tissue of origin.

Eosinophilic cholecystitis: an infrequent cause of acute cholecystitis.

Eosinophilic cholecystitis (EC) is a rare disease that is characterised by eosinophilic infiltration of the gallbladder. Its pathogenesis is unknown, although many hypotheses have been made. Clinical and laboratory manifestations do not differ from those of other causes of cholecystitis. Diagnosis is histological and usually performed after analysis of the surgical specimen. We report the case of a woman aged 24 years, with symptoms of fever, vomiting and pain in the right upper quadrant. When imaging tests revealed acalculous cholecystitis, an urgent cholecystectomy was performed. Histological examination of the surgical specimen revealed eosinophilic cholecystitis. No cause of the symptoms was found.

Colecistitis eosinofílica: causa infrecuente de colecistitis aguda / Eosinophilic cholecystitis: an infrequent cause of acute cholecystitis

La colecistitis eosinofílica (CE) es una enfermedad rara caracterizada por una infiltración eosinófila de la vesícular biliar. Su etiopatogenia es desconocida, aunque se han postulado múltiples hipótesis. Las manifestaciones clínicas y de laboratorio no difieren de otras causas de colecistitis. El diagnóstico es histológico y suele realizarse tras el análisis de la pieza quirúrgica. Presentamos el caso de una mujer de 24 años, con clínica de fiebre, dolor en hipocondrio derecho y vómitos. Las pruebas de imagen evidenciaban una colecistitis alitiásica, tras lo cual se realizó una colecistectomía urgente. Los hallazgos histológicos de la pieza quirúrgica revelaban una colecistitis eosinofílica. En este caso, no se encontró causa que justificase el cuadro

Eosinophilic cholecystitis (EC) is a rare disease that is characterised by eosinophilic infiltration of the gallbladder. Its pathogenesis is unknown, although many hypotheses have been made. Clinical and laboratory manifestations do not differ from those of other causes of cholecystitis. Diagnosis is histological and usually performed after analysis of the surgical specimen. We report the case of a woman aged 24 years, with symptoms of fever, vomiting and pain in the right upper quadrant. When imaging tests revealed acalculous cholecystitis, an urgent cholecystectomy was performed. Histological examination of the surgical specimen revealed eosinophilic cholecystitis. No cause of the symptoms was found

Ulcerated upper lip tumour: diagnostic procedure.

A Mediterranean Spanish woman, aged 56 years and in good health, presented with a nodule above her upper lip, which had rapidly evolved to central ulceration with crusting. As part of the work-up, samples were taken for microbiological and histopathological investigation. At the follow-up appointment the lesion had almost disappeared and a small fibrotic area of scarring remained. The diagnostic procedure to distinguish between localised cutaneous leishmaniasis and keratoacanthoma, both characterised by rapidly growing nodules on the face, is presented in this case-based article.

Cutaneous indurated plaque on the abdomen associated with diabetes mellitus.

A woman, 74 years of age, presented to the emergency department with a lesion on the lower abdominal wall that had started a month earlier and was not associated with any other symptoms. Her family physician had treated it with emollient creams. Relevant past medical history included congestive heart failure, hypertension, hypertensive heart disease, pulmonary hypertension, mitral regurgitation, chronic atrial fibrillation, rosacea and diabetes mellitus that was being treated with oral hypoglycaemics (metformin). Physical examination revealed an area of skin on the lower abdominal wall that was ill-defined and indurated, with whitish papules and a 'cobblestone' appearance (Figure 1).