José Aneiros-Fernández

A new perspective in Oral health: Potential importance and actions of melatonin receptors MT1, MT2, MT3, and RZR/ROR in the oral cavity

BACKGROUND Melatonin is involved in many physiological processes in mammals, amongst others; it is implicated in sleep-wake regulation. It has antioxidant and anti-inflammatory properties. It also acts as an immunomodulator, stimulates bone metabolism and inhibits various tumours. Additionally an abnormal melatonin rhythm may contribute to depression and insomnia. The mechanisms of action of melatonin include the involvement of membrane receptors (MT1, MT2), cytosolic binding sites (MT3 and calmodulin), and nuclear receptors of the RZR/ROR family. Melatonin also has receptor-independent activity and can directly scavenge free radicals. The current review addresses the functions of melatonin in the oral cavity in relation to its receptors. METHODS An extensive search was conducted on the following scientific databases Pub Med, Science Direct, ISI Web of Knowledge and Cochrane database in order to review all pertinent literature. RESULTS Melatonin from the blood into the saliva may play an important role in suppressing oral diseases. It may have beneficial effects in periodontal disease, herpes and oral cancer, amongst others. CONCLUSIONS Melatonin contributes to protecting of oral cavity from tissue damage due to its action of different receptors. From the reviewed literature it is concluded that experimental evidence suggests that melatonin can be useful in treating several common diseases of the oral cavity. Specific studies are necessary to extend the therapeutic possibilities of melatonin to other oral diseases.

Cardiovascular Risk Factors in Patients with Lichen Planus

BACKGROUND Chronic inflammation was found to play an important role in the development of cardiovascular risk factors. Recently a case-control study found that lichen planus was associated with dyslipidemia in a large series of patients. However, no data were presented about lipid values, glucose levels, or blood pressure. OBJECTIVE The objective of this case-control study was to evaluate cardiovascular risk factors included in Adult Treatment Panel III criteria for metabolic syndrome in men and women with lichen planus and in healthy controls. PATIENTS AND METHODS This case-control study included 200 patients, 100 with lichen planus (50 men and 50 women) and 100 controls consecutively admitted to the outpatient clinic in Dermatology departments in Granada, Spain. RESULTS Analysis of metabolic syndrome parameters revealed a higher significant prevalence of dyslipidemia in patients with lichen planus. No significant differences were observed in glucose levels, abdominal obesity, or blood pressure. Elevated levels of C-reactive protein, erythrocyte sedimentation rate, and fibrinogen were noted in patients with lichen planus. Adjusted odds ratio for dyslipidemia in patients with lichen planus was 2.85 (95% confidence interval, 1.33-5.09; P=.001). CONCLUSION Chronic inflammation in patients with lichen planus may explain the association with dyslipidemia. Lipid levels screening in men or women with lichen planus may be useful to detect individuals at risk and start preventive treatment against the development of cardiovascular disease.

Cortistatin Inhibits Migration and Proliferation of Human Vascular Smooth Muscle Cells and Decreases Neointimal Formation on Carotid Artery Ligation

Rationale: Proliferation and migration of smooth muscle cells (SMCs) are key steps for the progression of atherosclerosis and restenosis. Cortistatin is a multifunctional neuropeptide belonging to the somatostatin family that exerts unique functions in the nervous and immune systems. Cortistatin is elevated in plasma of patients experiencing coronary heart disease and attenuates vascular calcification. Objective: To investigate the occurrence of vascular cortistatin and its effects on the proliferation and migration of SMCs in vitro and in vivo and to delimitate the receptors and signal transduction pathways governing its actions. Methods and Results: SMCs from mouse carotid and human aortic arteries and from human atherosclerotic plaques highly expressed cortistatin. Cortistatin expression positively correlated with the progression of arterial intima hyperplasia. Cortistatin inhibited platelet-derived growth factor–stimulated proliferation of human aortic SMCs via binding to somatostatin receptors (sst2 and sst5) and ghrelin receptor, induction of cAMP and p38-mitogen–activated protein kinase, and inhibition of Akt activity. Moreover, cortistatin impaired lamellipodia formation and migration of human aortic SMCs toward platelet-derived growth factor by inhibiting, in a ghrelin-receptor–dependent manner, Rac1 activation and cytosolic calcium increases. These effects on SMC proliferation and migration correlated with an inhibitory action of cortistatin on the neointimal formation in 2 models of carotid arterial ligation. Endogenous cortistatin seems to play a critical role in regulating SMC function because cortistatin-deficient mice developed higher neointimal hyperplasic lesions than wild-type mice. Conclusions: Cortistatin emerges as a natural endogenous regulator of SMCs under pathological conditions and an attractive candidate for the pharmacological management of vascular diseases that course with neointimal lesion formation.

Melatonin and cancer: current knowledge and its application to oral cavity tumours

BACKGROUND Melatonin (MLT) is a molecule secreted by the pineal gland in cyclical periods. In mammals, MLT is involved in physiological processes, such as sleep/wake regulation in the circadian cycle. It has antioxidant and anti-inflammatory properties, functions as an immunomodulator, and stimulates bone metabolism. MLT is also involved in tumour processes in breast, prostate, liver, and bone cancers, among others, and in oral cavity tumours like epidermoid carcinoma. We are gradually increasing our knowledge of the underlying mechanism of MLT action in the aforementioned tumour processes, in which MT1, MT2, MT3, and RZR receptors appear to play a highly important role. These receptors belong to a large family of G-protein-coupled transmembrane receptors, some of which have been linked to melatonins anticancer action, to tumour growth, and to prognosis. The objective of this article is to provide a clear review of research into the range of MLT functions, focusing specifically on MT receptors. We aim to contribute interesting, new approaches to research into oral cavity tumours. METHODS An extensive review of the research literature was conducted using PubMed, Science Direct, ISI Web of Knowledge, and the Cochrane base. RESULTS This study highlights the growing importance of MLT in the prognosis and treatment of certain tumours, including epidermoid carcinoma in the oral cavity. Moreover, it opens up a highly original, encouraging line of research in the field of tumours. CONCLUSIONS MLT contributes to protecting the oral cavity from tissue damage caused by receptor action. Experimental evidence suggests that it may be useful in the treatment and prognosis of tumour processes in the oral cavity.

A Novel Histochemical Method for a Simultaneous Staining of Melanin and Collagen Fibers

For the histopathologic diagnosis of melanocytic lesions, it could be necessary to identify the melanin pigment because its visualization is unspecific with hematoxylin-eosin (HE). The Fontana-Masson (FM) technique is used in histopathology in this type of lesion, which allows the identification of the pigment, but it loses all the morphologic parameters. The authors describe a modification to the FM method, for the evaluation of the morphology, the argentaffin reaction of the melanin, and collagens fibers of the extracellular matrix simultaneously, for which they have developed the Fontana-Masson picrosirius (FMPS) method. Biopsies of different melanocytic lesions were used for the performance of the HE, FM, and FMPS methods. The pixel intensity of the reaction for melanin, collagen, and epithelium was determined with ImageJ software. The FMPS method allows the evaluation of morphological characteristics, identifying the melanin pigment and collagen fibers with high intensity simultaneously. This method does not differ significantly from FM in the identification of melanin, maintaining its sensitivity and specificity. In addition, it does not differ in the demonstration of the morphology with HE. However, FMPS is significantly superior in the identification of collagen fibers. The FMPS method combines morphological and histochemical parameters that could be useful in the study of pigmented lesions of melanocytic origin.

Glypican 3 is a sensitive, but not a specific, marker for the diagnosis of yolk sac tumours.

Sir: The recent study of Zynger et al. analyses glypican 3 (GLP3) as an alternative marker to a-fetoprotein (AFP) in the diagnosis of yolk sac tumours (YSTs). The authors report that GLP3 has a higher sensitivity than AFP. We evaluated immunostaining patterns of GLP3 and other germ cell tumour markers in a series of 28 testicular germ cell tumours, and correlated them with those present in normal embryonal tissues. Although our findings confirmed that GLP3 has a high sensitivity for YST areas, they also revealed that GLP3 is not wholly specific, as it can also be positive in other types of germ cell tumour. We performed GLP3 immunohistochemistry (clone 1G12, prediluted; Bio Mosaics, Burlington, VT, USA) in a randomly selected series of 28 recent cases of testicular germ cell tumour. There were seven pure seminomas, one of which had a syncytiotrophoblastic component, two pure embryonal carcinomas, and one case of pure YST. Sixteen mixed germ cell tumours showed the following components: five seminomas, 12 embryonal carcinomas, 11 YSTs, 11 teratomas and five chorionic areas. The remaining two cases were a pure carcinoid and a spermatocytic seminoma. As expected, the YST patterns were mixed, and contained the usual reticular–microcystic (nine cases), glandular–alveolar (eight cases) and hepatic (two cases) phenotypes. Tumours were additionally analysed for AFP (polyclonal, prediluted), placental-like alkaline phosphatase (PLAP) (clone 8A9, prediluted), D2-40 (clone D-40, prediluted) and CD30 (clone BerH2, prediluted), all from Dako Denmark A ⁄ S Glostrup, as well as OCT3 ⁄ 4 (clone C-10, prediluted; Master Diagnostica, Granada, Spain). For the correlation of tumour tissue with early embryonal tissues, an 11th-week embryo and an 8th-week embryo, with a histologically normal secondary yolk sac, were studied, together with their placentas, using the same antibodies. Our results showed that, in the placenta, GLP3 had membranous and ⁄ or cytoplasmic positivity for syncytiotrophoblast and the mesenchymal cells of the villous cores (Figure 1A), and was negative in the cytotrophoblast. In the secondary human yolk sac, it showed strong, membranous and cytoplasmic positivity for the cells lining the endodermal yolk sac tubules (Figure 1B), delineating intercellular and intracellular lumina (Figure 1B, inset). In somatic embryonal tissues, GLP3 showed marked granular cytoplasmic positivity in the liver and apical positivity in the renal proximal tubules and epithelium of Bowman’s capsule. The neuroepithelium was also positive (Figure 1C). Weak positivity was also observed in the pulmonary epithelium and the acinary cells of the pancreas. In the 12 cases containing areas of various YST patterns, cytoplasmic GLP3 positivity was strong in both the reticular–microcystic (Figure 1D) and glandular–alveolar components, and GLP3 showed marked granular cytoplasmic overexpression in areas of hepatic YST (Figure 1E). Although the GLP3 immunoreactivity was broadly parallel to that of AFP, for GLP3 there was an increased number of positive tissue areas with more intense staining. Background staining was absent for GLP3 but prominent for AFP (Figure 1D,E). Embryonal carcinoma areas were identified by both their characteristic histology and their marked, diffuse coexpression of CD30 and OCT3 ⁄ 4. However, eight cases also showed GLP3 staining, which was focal in seven cases and diffuse in one (Figure 1F,G). GLP3 positively stained the primitive endodermal cavities of embryoid bodies present in one case of embryonal carcinoma (Figure 1H). Trophoblastic areas associated with embryonal carcinoma also showed membranous and cytoplasmic GLP3 positivity in the syncytia of three of the five cases (Figure 1I). However, both the cytotrophoblastic component of these areas and the isolated syncytiotrophoblastic cells found in a pure seminoma were negative. Teratomatous somatic tissues also showed GLP3 positivity in otherwise AFP-negative, morphologically non-YST foci. It occurred in immature, narrow glands (five cases), periglandular immature stroma (three cases), foci of cartilage (two cases), intestinal-type glands (Figure 1J) (one case) and neuroepithelial structures (Figure 1K) (one case). Seminoma and intratubular germ cell neoplasia were positive for PLAP, D2-40 and OCT3 ⁄ 4, but were both consistently negative for GLP3. Normal adjacent testicular tubules never expressed GLP3. Spermatocytic seminoma showed intense granular positivity in its large-cell component (Figure 1L) as well as some membranous positivity in intermediate cells.

Myositis Ossificans Circumscripta Without History of Trauma

UNLABELLED Myositis ossificans circumscripta is a form of heterotopic ossification that is benign in nature associated to a trauma, but may appear clinically and radiologically as a malignant neoplasm. We describe a rare case of calcifying of myositis ossificans not associated to trauma in a 35-year-old woman with a mass in her upper third and external of right thigh. We discuss some of the difficulties of diagnosis and histological evolution of the lesion. KEYWORDS Myositis ossificans; Thigh; Differential diagnosis; Nontraumatic.

Cutaneous metastases in renal cell carcinoma: a case report

Renal cell carcinoma is the most common form of malignant renal tumour and is extremely lethal. About 25% of the patients develop metastasis at the time of diagnosis, and in many cases during the course of the disease, affecting the lung, lymphatic ganglions, liver, and bone, with skin metastases being quite rare.A 73-year-old patient, who had undergone surgery for adenocarcinoma in the left kidney 10 years previously, visited the dermatological service due to the appearance of recent, rapidly-developing lesion at the back of his neck. It was decided to remove it surgically. The histological study confirmed clear cell carcinoma that was probably of renal origin. A computed tomography scan was performed on the thorax and abdomen, and lesions were observed that were compatible with metastasis in the right kidney and left lung. Treatment with a multikinase angiogenesis inhibitor (sunitib) was started.Due to the late development of the skin metastases and those in other regions that worsen the prognosis, these patients must be subjected to long-term clinical observation. Urologist should pay attention to cutaneous lesion appearing in these patients as in many times they look like benign lesion.

Primary cutaneous and subcutaneous leiomyosarcomas: evolution and prognostic factors

Cutaneous and subcutaneous leiomyosarcomas (LMS) are uncommon neoplasms. We reviewed the MEDLINE database to assess their rates of recurrence and metastasis, mortality and recommended follow-up period. Other prognostic factors were also studied. This review included 112 subcutaneous LMS and 313 cutaneous LMS. In subcutaneous LMS, we observed that rates of recurrence, metastasis and mortality were 36.63%, 43.23% and 37.82%, respectively, after a median follow-up period of 4.40 years, while in cutaneousLMSthose figures were 24.40%, 4.22% and 3.33%, respectively, after a median follow-up period of 3.45 years. Although subcutaneous and cutaneous LMS show similar morphologic features, the latter show less tendency to recur and metastasize; in certain cases they both may be the cause of death. For these reasons we suggest avoiding the term “atypical intradermal smooth muscle neoplasm”. Location, size and histologic grade are essential prognostic factors for superficial LMS. Recurrence after incomplete excision can be avoided when performed with a surgical margin of at least 1 cm. Follow-up should be at least five years.

Poly(ADP-Ribose) Polymerase-1 Expression Is Related To Cold Ischemia, Acute Tubular Necrosis, and Delayed Renal Function In Kidney Transplantation

Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD) transplantation. Ischemia-reperfusion (IR) injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1) activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN). Materials and Methods Nuclear PARP-1 immunohistochemical expression was studied in 326 paraffin-embedded renal allograft biopsies (193 with different degrees of ATN and 133 controls) and in murine Parp-1 knockout model of IR injury. Results PARP-1 expression showed a significant relationship with cold ischemia time (r coefficient = 0.603), time to effective diuresis (r = 0.770), serum creatinine levels at biopsy (r = 0.649), and degree of ATN (r = 0.810) (p = 0.001, Pearson test). In the murine IR model, western blot showed an increase in PARP-1 that was blocked by Parp-1 inhibitor. Immunohistochemical study of PARP-1 in kidney allograft biopsies would allow early detection of possible delayed renal function, and the administration of PARP-1 inhibitors may offer a therapeutic option to reduce damage from IR in donor kidneys by preventing or minimizing ATN. In summary, these results suggest a pivotal role for PARP-1 in the ATN of renal transplantation. We propose the immunohistochemical assessment of PARP-1 in kidney allograft biopsies for early detection of a possible delayed renal function.