Habitat preference and flowering-time variation contribute to reproductive isolation between diploid and autotetraploid Anacamptis pyramidalis.

Tetraploid lineages are typically reproductively isolated from their diploid ancestors by post-zygotic isolation via triploid sterility. Nevertheless, polyploids often also exhibit ecological divergence that could contribute to reproductive isolation from diploid ancestors. In this study, we disentangled the contribution of different forms of reproductive isolation between sympatric diploid and autotetraploid individuals of the food-deceptive orchid Anacamptis pyramidalis by quantifying the strength of seven reproductive barriers: three prepollination, one post-pollination prezygotic and three post-zygotic. The overall reproductive isolation between the two cytotypes was found very high, with a preponderant contribution of two prepollination barriers, that is phenological and microhabitat differences. Although the contribution of post-zygotic isolation (triploid sterility) is confirmed in our study, these results highlight that prepollination isolation, not necessarily involving pollinator preference, can represent a strong component of reproductive isolation between different cytotypes. Thus, in the context of polyploidy as quantum speciation, that generates reproductive isolation via triploid sterility, ecological divergence can strengthen the reproductive isolation between cytotypes, reducing the waste of gametes in low fitness interploidy crosses and thus favouring the initial establishment of the polyploid lineage. Under this light, speciation by polyploidy involves ecological processes and should not be strictly considered as a nonecological form of speciation.

Experimental new automatic tools for robotic stereotactic neurosurgery: towards "no hands" procedure of leads implantation into a brain target.

The use of robotics in neurosurgery and, particularly, in stereotactic neurosurgery, is becoming more and more adopted because of the great advantages that it offers. Robotic manipulators easily allow to achieve great precision, reliability, and rapidity in the positioning of surgical instruments or devices in the brain. The aim of this work was to experimentally verify a fully automatic "no hands" surgical procedure. The integration of neuroimaging to data for planning the surgery, followed by application of new specific surgical tools, permitted the realization of a fully automated robotic implantation of leads in brain targets. An anthropomorphic commercial manipulator was utilized. In a preliminary phase, a software to plan surgery was developed, and the surgical tools were tested first during a simulation and then on a skull mock-up. In such a way, several tools were developed and tested, and the basis for an innovative surgical procedure arose. The final experimentation was carried out on anesthetized "large white" pigs. The determination of stereotactic parameters for the correct planning to reach the intended target was performed with the same technique currently employed in human stereotactic neurosurgery, and the robotic system revealed to be reliable and precise in reaching the target. The results of this work strengthen the possibility that a neurosurgeon may be substituted by a machine, and may represent the beginning of a new approach in the current clinical practice. Moreover, this possibility may have a great impact not only on stereotactic functional procedures but also on the entire domain of neurosurgery.

A randomized-controlled, double-blind study of the impact of selenium supplementation on thyroid autoimmunity and inflammation with focus on the GPx1 genotypes.

PURPOSE: To analyze the impact of selenium supplementation on serum antiTPO levels and thyroid echogenicity in patients with CAT, evaluating the response in subgroups with different GPx1 genotypes. METHODS: CAT patients (n = 55) with positive antiTPO were randomized to selenomethionine (SeMet) 200 µg daily (n = 28) or placebo (n = 27) for 3 months. Assessments included GPx1 genotyping at baseline and serum levels of plasma selenium, erythrocyte GPx1 activity, antiTPO and thyroid echogenicity at baseline, and 3 and 6 months. RESULTS: In the SeMet group, the increase in plasma levels of selenium and erythrocyte GPx1 activity was similar among patients with different GPx1 genotypes. In the overall cohort, patients randomized to SeMet showed a 5 % decrease in antiTPO levels at 3 months (p = non-significant) and 20 % at 6 months (p < 0.001 versus 3 months). In contrast, patients in the placebo group did not show significant changes in antiTPO levels at any time point. Subgroup analysis showed that patients with different GPx1 genotypes presented comparable responses in antiTPO levels and echogenicity index to SeMet. CONCLUSIONS: Selenium supplementation decreased serum antiTPO levels in CAT patients, with similar response among patients with different GPx1 genotypes.

A follow-up study of the chronic kidney disease patients treated with Brazil nut: focus on inflammation and oxidative stress.

Brazil nut is the richest known food source of selenium. The supplementation with Brazil nut during 3 months was effective in reducing oxidative stress and inflammation in hemodialysis (HD) patients. However, there are no available data on the antioxidant effect after that supplementation. The objective of this work was to determine if the beneficial effects of one Brazil nut supplementation per day during 3 months for the HD patients could be sustained after 12 months. Twenty-nine HD patients (58.6 % men, 51.0 ± 3.3 years) from RenalCor Clinic, Rio de Janeiro, Brazil, were followed up 12 months after the supplementation study had finished. The plasma levels of antioxidant substances as selenium, glutathione peroxidase (GPx), 8-isoprostane, 8-hydroxy-2-deoxyguanosine (8-OHdG) and cytokines (tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6)) were determined before, after 3 months of supplementation and after 12 months. After 3-months supplementation, cytokines, 8-OHdG and 8-isoprostane plasma levels have decreased and the activity of GPx and selenium plasma levels have increased significantly. Additionally, after 12 months, the values of 8-isoprostane, 8-OHdG and cytokines increased and the activity of GPx and selenium plasma levels decreased significantly. The levels of oxidative stress and inflammation biomarkers after 12 months increased compared to the basal levels. Consequently, it is necessary to motivate patients to adopt different dietary intake patterns.

Analysis of plasma and erythrocyte zinc levels in premenopausal women with breast cancer.

INTRODUCTION: Zinc deficiency has been associated with damage and oxidative changes in DNA that may increase an individual's risk of cancer. Furthermore, zinc metabolism may be affected in cancer patients, leading to alterations in its distribution that would favor carcinogenesis. Plasma and erythrocyte zinc levels in women with breast cancer were evaluated in this cross-sectional, controlled study. MATERIAL AND METHODS: Fifty-five premenopausal women of 25 to 49 years of age with and without breast cancer were divided into two groups: Group A, composed of women without breast cancer (controls, n = 26) and Group B, composed of women with breast cancer (cases, n = 29). Plasma and erythrocyte zinc levels were measured by flame atomic absorption spectrophotometry at γ = 213.9 nm. Diet was assessed using the 3-day diet recall method and analyzed using the NutWin software program, version 1.5. Student's t-test was used to compare means and significance was established at p = 0.05. RESULTS: Mean plasma zinc levels were 69.69 ± 9.00 g/dL in the breast cancer patients and 65.93 ± 12.44 g/dL in the controls (p = 0.201). Mean erythrocyte zinc level was 41.86 ± 8.28 µgZn/gHb in the cases and 47.93 ± 7.00 µgZn/gHb in the controls (p < 0.05). In both groups, dietary zinc levels were above the estimated average requirement. CONCLUSIONS: The present results suggest that zinc levels are lower in the erythrocyte compartment of pre-menopausal women with breast cancer.

Novel missense mutations and unexpected multiple changes of RYR1 gene in 75 malignant hyperthermia families.

Malignant hyperthermia (MH) is an autosomal dominant pharmacogenetic disorder of skeletal muscle characterized by disturbance of intracellular calcium homeostasis in the sarcoplasmic reticulum. Mutations of the ryanodine receptor 1 (RYR1) gene account for most cases, with some studies claiming up to 86% of mutations in this locus. However, RYR1 gene is large and variants are common even in the normal population. We examined 54 families with MH susceptibility and 21 diagnosed with equivocal MH. Thirty-five were selected for an anesthetic reaction, whereas the remainder for hyperCKemia. In these, we studied all 106 exons of the RYR1 gene. When no mutation was found, we also screened: sodium channel voltage-gated, type IV alpha subunit (SCN4A), calcium channel voltage-dependent, L type, alpha 1S subunit (CACNA1S), and L-type voltage-gated calcium channel alpha 2/delta-subunit (CACNL2A). Twenty-nine different RYR1 mutations were discovered in 40 families. Three other MH genes were tested in negative cases. Fourteen RYR1 amino acid changes were novel, of which 12 were located outside the mutational 'hot spots'. In two families, the known mutation p.R3903Q was also observed in malignant hyperthermia-nonsusceptible (MHN) individuals. Unexpectedly, four changes were also found in the same family and two in another. Our study confirms that MH is genetically heterogeneous and that a consistent number of cases are not due to RYR1 mutations. The discordance between in vitro contracture test status and the presence of a proven causative RYR1 mutation suggests that the penetrance may vary due to as yet unknown factors.

Follow-up of patients tested for malignant hyperthermia susceptibility.

BACKGROUND AND OBJECTIVE: Malignant hyperthermia is an inherited disorder of skeletal muscle characterized by muscle contracture and hypermetabolic crisis following exposure to halogenated anaesthetics and depolarizing muscle relaxants. We planned this follow-up to get more information about the safety of non-triggering anaesthesia in susceptible patients; the safety of the use of trigger agents in non-susceptible patients and any minor sequelae following the biopsy. METHODS: A questionnaire was sent to 244 patients tested for susceptibility between 1998 and 2004 enquiring about sequelae from the biopsy, subsequent experience with anaesthesia and difficulties encountered because of the investigation. RESULTS: Replies were received from 129 patients. Thirty-four complained about sequelae from the biopsy: 10 reported headache and nausea; 16 experienced pain and a lack of strength in the biopsed leg and 8 found the scar less than satisfactory. Ten patients found it difficult to find a diagnostic centre. Eighteen reported problems and/or delay when they had needed a subsequent anaesthetic. Fourteen patients found the anaesthesiologist reluctant to anaesthetize them and four experienced a delay. Forty-three patients received anaesthesia since their biopsy. Complete medical records were available for 24 anaesthetic exposures in 23 patients. No documented perioperative complications occurred. Only three non-susceptible patients received one trigger agent. CONCLUSIONS: It is safe to use trigger-free anaesthesia in susceptible patients. The difficulties encountered by patients to be anaesthetized and the management of the majority of non-susceptible patients during general anaesthesia show the need of more accurate educational programmes and methods for promoting patient-centred care.

Mutations in the RYR1 gene in Italian patients at risk for malignant hyperthermia: evidence for a cluster of novel mutations in the C-terminal region.

Mutations in the ryanodine receptor type 1 (RYR1) gene are associated with Malignant Hyperthermia (MH) and Central Core Disease (CCD). We report here on the molecular analysis of the RYR1 gene in Italian families referred as potential cases of MH or in patients with CCD or multicore/minicore myopathy. Of a total of 20 individuals with mutations in the RYR1 gene, 14 were part of a group of 47 MH susceptible (MHS) patients, 4 of 34 individuals diagnosed as MH equivocal (MHE), and 2 were patients diagnosed with minicore myopathy and CCD, respectively. Mutations were found to segregate with the MHS or MHE phenotype within the families of the probands. A discordance between phenotype and genotype was observed in a family where a mutation detected in an MHS proband was also found in the father who had been diagnosed MH normal (MHN) at the IVCT. In addition to known mutations, seven novel mutations were found, five of which occurred in exons encoding the C-terminal region of RYR1. These results indicate that the C-terminal region of RYR1 represents an additional hot spot for mutations in patients with MH, similar to what has been reported for patients with CCD.

Suppression of natural killer cell function and production of soluble ICAM-1: endometrial stroma versus melanoma.

PROBLEM: It has been suggested that specific mechanisms commonly used by different cellular systems to evade immunologic recognition are involved in the development of endometriosis. To gain insight into this aspect, we looked at the relationship between two of these mechanisms in endometrial stroma and the melanoma system for which the ability to create an environment of immune privilege has been well established. METHOD OF STUDY: Media conditioned by endometrial stromal cultures and malignant melanoma A375 were examined to test their effects on peripheral blood mononuclear cell-mediated cytotoxicity directed against K562 target. Moreover, these media were tested for the concentration of the soluble form of intercellular adhesion molecule-1 (sICAM-1), which has been suggested as a marker for spreading potential. RESULTS: Media conditioned by endometrial stromal cultures exerted a significant suppressive effect on cell cytotoxicity when compared with those derived from malignant melanoma Moreover, the constitutive release of sICAM-1 was significantly higher in supernatants from endometrial stromal than in melanoma cells. CONCLUSIONS: These results indicate that two specific properties suggested to be involved in the ability of tumor cells to evade the immune system are more pronounced in the endometrium than in a malignant melanoma. Since the properties evaluated have been previously demonstrated to be even more notable in endometrial samples derived from endometriosis patients, a role of these mechanisms in the development of the disease may be hypothesized.

[Utilization of different iron concentrations on pregnant adolescents also supplemented with zinc and folate]. / Utilização de diferentes concentrações de ferro por adolescentes grávidas também suplementadas com zinco e ácido fólico.

The pregnant teenager is considered at nutritional risk specially due to the fact that most of them still growing and developing. Therefore the demands of pregnancy compete with those of growth causing an extra need for her and the fetus (1). Iron, zinc and folate are essential nutrients that are frequently low on the teenagers diet. Besides that there is not much specific information available about these nutrient recommendations and their interaction among each other. The data available is limited and demands more investigation. This study was conducted at a Public Maternity Hospital located at Teresina, Piauf, Brazil. The main objective of this study was to investigate the effect of different concentrations of iron supplementation (80 and 120 mg of ferrous sulfate) together with folate (250 micrograms) and zinc (5 mg) on the hemoglobin concentration and iron stores (plasma ferritin) of pregnant adolescents. The supplementation was done from the 16th to 20th weeks of gestation until delivery. The data founded proved that either 80 mg or 120 mg of iron supplements had similar effect on the improvement of hemoglobin concentration although results showed no statistical significance.

Dynamic aspects of endometriosis in a mouse model through analysis of implantation and progression.

The aim of this study was to use normal immunocompetent mice to set up a model for endometriosis which allowed to study the dynamic aspects involved in initiation and progression of the disease. Thirty mice were surgically transplanted with autologous endometrium and at 3 weeks showed evidence of endometriosis. Diagnosis of endometriotic lesions was histologically confirmed. Visual inspection using a caliper revealed that, after an initial decrease in size (from 33.44+/-2.33 mm2 to 24.24+/-2.37 mm2 (p<0.01)) detected at 3 weeks after transplantation, there was a significant increase of lesion area from 21.30+/-3.15 mm2 to 43.93+/-6.29 mm2 (p<0.05) in the following 4 weeks. When we compared these results to those obtained in mice which underwent bilateral annessiectomy, we observed that, when bilateral annessiectomy was performed simultaneously to endometrial transplantation, lesion surfaces were similar between mice which were or were not subjected to bilateral ovariectomy. On the other hand, when bilateral annessiectomy was performed at second laparotomy and then evaluated after 4 weeks, differently from what observed in control mice, surface values decreased from 21.24+/-2.29 mm2 to 10.58+/-3.40 mm2 (p<0.01). Finally, progression of lesions in estrogen supplemented mice seems less evident than in control mice since only a slight but not significant increase in size (from 21.32+/-3.32 mm2 to 26.18+/-6.98 mm2, p=0.32) was detected. The results presented herein demonstrate that surgically induced endometrial implants in mice are dynamic lesions and that implantation and progression of endometriosis represent different stages in the ethiopathogenesis of the disease. Moreover, we showed that progression, but not implantation, of ectopic endometrium is dependent upon the functionally and structurally integrity of the ovaries. This is a model of endometriosis established in normal immunocompetent mice, and, consequently, may represent a reliable tool for testing new immunological therapeutical approaches and studying the role of different genes using transgenic mice.

Mutation screening of the RYR1 gene and identification of two novel mutations in Italian malignant hyperthermia families.

Point mutations in the ryanodine receptor (RYR1) gene are associated with malignant hyperthermia, an autosomal dominant disorder triggered in susceptible people (MHS) by volatile anaesthetics and depolarising skeletal muscle relaxants. To date, 17 missense point mutations have been identified in the human RYR1 gene by screening of the cDNA obtained from muscle biopsies. Here we report single strand conformation polymorphism (SSCP) screening for nine of the most frequent RYR1 mutations using genomic DNA isolated from MHS patients. In addition, the Argl63Cys mutation was analysed by restriction enzyme digestion. We analysed 57 unrelated patients and detected seven of the known RYR1 point mutations. Furthermore, we found a new mutation, Arg2454His, segregating with the MHS phenotype in a large pedigree and a novel amino acid substitution at position 2436 in another patient, indicating a 15.8% frequency of these mutations in Italian patients. A new polymorphic site in intron 16 that causes the substitution of a G at position -7 with a C residue was identified.

In vitro contracture test for diagnosis of malignant hyperthermia following the protocol of the European MH Group: results of testing patients surviving fulminant MH and unrelated low-risk subjects. The European Malignant Hyperthermia Group.

BACKGROUND: Determination of sensitivity and specificity of the in vitro contracture test (IVCT) for malignant hyperthermia (MH) susceptibility using the European MH Group (EMHG) protocol has been performed in some laboratories but only on a small sample from the combined EMHG. Thus, the purpose of the present study was to determine combined EMHG sensitivity and specificity of the test. METHODS: Results of IVCT of patients with previous fulminant MH and normal, low-risk subjects (controls) were collected from 22 centres of the EMHG. IVCT was performed according to the EMHG protocol. Patients were included in the study if the clinical crisis had a score of at least 50 points with the Clinical Grading Scale. Low-risk subjects were included provided they did not belong to a family with known MH susceptibility, they had not developed any signs of MH at previous anaesthetics, and they did not suffer from any neuromuscular disease. For inclusion of both MH patients and low-risk subjects, at least 1 muscle bundle in the IVCT should have twitches of 10 mN (1 g) or more. For evaluation of individual tests, only muscle bundles with twitch heights of 10 mN (1 g) or more were used. RESULTS: A total of 1502 probands had undergone IVCT because of a previous anaesthesia with symptoms and signs suggestive of MH. Of these, 119 had clinical scores of 50 and above. From these 119 MH-suspected patients and from 202 low-risk subjects, IVCT data were collected. Subsequently, 14 MH-suspected patients were excluded from further analysis for the following reasons: In 3 patients, the suspected MH episode could be fully explained by diseases other than MH; in 11 MHS patients, IVCT was incomplete (n = 1), data were lost (n = 3), or none of the muscle bundles fulfilled twitch criteria (n = 7). Of the remaining 105 MH-suspected patients, 89 were MHS, 10 MHEh, 5 MHEc, and one MHN. Thus, we observed a diagnostic sensitivity of the IVCT of 99.0% if the MHE group is considered susceptible (95% confidence interval 94.8-100.0%). Of the 202 low-risk subjects, 3 were MHS, 5 MHEh, 5 MHEc, and 189 MHN. This gives a specificity of the IVCT of 93.6% (95% confidence interval 89.2-96.5%). CONCLUSION: The IVCT for diagnosis of MH susceptibility in Europe has a high sensitivity and a satisfactory specificity.

[Effect of supplementation with peach palm as source of vitamin A: study with rats]. / Efeito da suplementação com pupunha como fonte de vitamina A em dieta: estudo em ratos.

The effect of supplementation with peach palm (Bactris gasipaes H.B.K.), as an alternative source of vit. A, in the regional diet of Manaus, AM, Brazil, in which the pulp was cooked and transformed into flour, was studied. The biological trial involved rats which were depleted in zinc and vitamin A, followed by repletion using the regional diet (RD), RD plus peach palm and RD plus vitamin A. The parameters used to determine the utilization of vitamin A were the vitamin A concentrations in the liver and plasma, and the growth of the animals. The diet was prepared according to the data of Shrimpton and Giugliano for families earning less than two legal minimum salaries. Adult post-partum rats were used, with six male pups each, which received a diet based on casein washed with 1% EDTA, without the addition of zinc or vitamin A for a period of 25 days, for the purpose of obtaining newly-weaned animals which were deficient in Zn and Vit.A. A control group received a diet also based on casein washed with 1% EDTA, but with all the nutrients in the quantities suggested by the Committee on Laboratory Animal Diets. The repletion period of the newly-weaned rats was of 30 days and the experimental design was entirely randomized with four groups of eight rats each. The diet supplementation followed the recommendations of the Committee on Laboratory Animal Diets. At the end of the experiment, it was observed that rats which consumed the diet based on the regional diet of Manaus supplemented with either peach palm or vitamin A showed a significantly greater concentration of vitamin A in the liver, 43.3 +/- 6.5 micrograms/g, 42.0 +/- 4.3 micrograms/g, respectively in relation to the regional diet, 5.5 +/- 1.1 micrograms/g (p < 0.05). The amount of zinc present in the regional diet, 10.7 mg per day, was bioavailable as determined by the concentration of zinc in the femurs. The results suggest that the regional diet of Manaus needs to be supplemented with vitamin A to maintain the hepatic reserves, and that such supplementation can be accomplished with peach palm, an abundant local commodity.

[Interaction of vitamin A and zinc in lactating rats. Experimental deficiency model]. / Interação de zinco e vitamina A em ratos na lactação. Modelo de deficiência experimental.

An experimental deficiency model of vitamin A and zinc in lactating rats was developed. The experimental design consisted in a depletion period of 4 weeks immediately after birth where test group animal received a casein based feed, deficient in zinc and vitamin A, and a control feed according to the recommendations of the Committee on Laboratory Animal Diets. Female Rathus norvergicus, var albinus (Rodentia, Mammalia) with 6 young males each were used. These came from the Biotério of the Faculdade de Ciências, Farmacêuticas of USP. At the end of the depletion period it was found that the weight of the males control group (109.1 g +/- 3.9 g) was significantly greater than that of the test group (40.8 g +/- 6.7 g). The same was true for the concentration of zinc in the femurs of these animals, in the control group the concentration was significantly greater (115.7 micrograms/g +/- 5.4 micrograms/g) than in the test group (35.5 micrograms/g +/- 3.3 micrograms). The concentration of vitamin A in the plasma of the control group (31.5 micrograms/dL +/- 2.5 micrograms/dL) also was significantly greater than the test group animals (8.9 micrograms/dL +/- 3.4 micrograms/dL). The concentration of hepatic vitamin A was similar for both groups. We can conclude that there was interaction of zinc and vitamin A, by liver and depletion in zinc. Although the plasmatic concentration of vitamin A indicates a depletion, this cannot be considered as total because of the hepatic reserves.

Role of immunosuppression in recurrence after liver transplantation for diethylnitrosamine-induced tumors in rats.

Hepatocellular carcinoma is one of the world's most common malignant diseases, with an increasing incidence related to liver cirrhosis. The purpose of the study was to evaluate the role of immunosuppression in recurrence in rats transplanted after liver tumor induction by diethylnitrosamine (DENA), which has proved to be a reliable carcinogen. In 14-week-old Lewis rats weighing 200 g, tumors were induced by the oral administration (5 mg/100 ml in drinking water ad libitum) of DENA for 13 weeks. Orthotopic liver transplantation (OLT) was performed after 4 weeks' latency. In the Lewis/Lewis rats weighing 200 g, tumors sporin A (CsA) treatment, median survival was 199-days with no recurrence or metastasis. In the BN/Lewis group with no CsA (5 ats) median survival was 144 days. All rats died due to rejection. In the other BN/Lewis group (10 rats), OLT was followed by CsA administration (7.5 mg/kg). Median survival was 161 days. In three rats (218 days), there was liver tumor recurrence; in two rats (137.5 days), kidney and lung metastases were found. The remaining rats died of septic complications. In the Lewis/Lewis + CsA group (10 rats), median survival was 131 days with 5 recurrencies and/or metastases. Two rats are still surviving at 84 and 88 days. Our results suggest that the DENA model is reliable; it proved to have a similar carcinologic pattern to HCC in man. Moreover, immunosuppression seems to play an important role in determining recurrence. Further studies are needed to investigate the efficacy of chemotherapy agents pre- and post-transplantation.

[Iron supplementation effects on zinc bioavailability in a regional diet of northeastern Brazil]. / Efeito da suplementação com ferro na biodisponibilidade de zinco em uma dieta regional do nordeste do Brasil.

The effects of supplementation with iron on the zinc bioavailability of the regional diet of northeastern Brazil (RDN), were investigated. One assay with Wistar rats, feed on RDN and control diets was carried out. The RDN diets contained 16 mg Zn/kg and levels of 35 mg, 70 mg and 140 mg Fe/kg, respectively. The control diets were prepared according to the standards of the Committee on Laboratory Animal Diets, with levels of protein, iron and zinc identical to those of RDN diets. Index of apparent absorption and zinc retained in the femur of the animals were the parameters utilized to measure zinc bioavailability. The results demonstrated that the supplementation with iron decreased the zinc bioavailability, and the effects were seen to affect diet quality and the Fe:Zn ratio. This fact must be taken into consideration in practices such as the fortying of foodstuffs and the administration of vitamin-mineral supplements to populations with nutritional deficiencies.

[Gardner's syndrome]. / La sindrome di Gardner.

The Gardner syndrome is characterized by polyposis coli and multiple hard and soft tissue tumors. This work show crucial dentist's role in the early diagnosis important for the highly malignant potential of this syndrome.