Systemic Capillary Leak Syndrome triggered by SARS-CoV2 infection: Case Report and Systematic Review.

Objective: Systemic capillary leak syndrome (SCLS) is a severe condition characterized by the coexistence of hypovolaemic shock, haemococentration, and hypoalbuminaemia, without albuminuria, that may progress to multiorgan failure and an unfavourable outcome. Its development is often triggered by viral infections, such as influenza A virus, but it is unclear whether it is also triggered by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We aimed to investigated the association between SARS-CoV-2 and SCLS.Method: We present the case of a 55-year-old-woman affected by SARS-CoV-2 infection who developed SCLS. Moreover, we performed a systematic review of the literature to identify any common features with other cases and to describe clinical characteristics and outcomes.Results: We found three other cases of SCLS occurring during SARS-CoV-2 infection in 2020. Taking all cases together, the mean age was 50 years (range 38-63), with a 1:1 gender ratio. Respiratory manifestations were the most common symptom, and all patients required admission to the intensive care unit. The mortality rate was 50%.Conclusions: SARS-CoV-2 infection may trigger SCLS disease, either by an overproduction of proinflammatory cytokines or by direct viral infection of the endothelium. Since SCLS may have a poor prognosis, in every SARS-CoV-2-infected patient presenting the suggestive triad of hypovolaemic shock, haemoconcentration, and hypoproteinaemia, an SCLS diagnosis should be considered and early treatment initiated.

[The cerebellum as a major player in motor disturbances related to Autistic Syndrome Disorders]. / Le cervelet comme acteur majeur dans les troubles moteurs des syndromes autistiques.

SCIENTIFIC BACKGROUND: Autism spectrum disorders (ASD) are neurodevelopmental disorders associated with disturbances in communication, social interactions, cognition and affect. ASD are also accompanied by complex movement disorders, including ataxia. A special focus of recent research in this area is made on the striatum and the cerebellum, two structures known not only to control movement but also to be involved in cognitive functions such as memory and language. Dysfunction within the motor system may be associated with abnormal movements in ASD that are translated into ataxia, abnormal pattern of righting, gait sequencing, development of walking, and hand positioning. This line of study may generate new knowledge and understanding of motor symptoms associated with ASD and aims to deliver fresh perspectives for early diagnosis and therapeutic strategies against ASD. AIMS OF THE REVIEW: Despite the relative paucity of research in this area (compared to the social, linguistic, and behavioural disturbances in ASD), there is evidence that the frontostriatal motor system and/or the cerebellar motor systems may be the site of dysfunction in ASD. Indeed, the cerebellum seems to be essential in the development of basic social capabilities, communication, repetitive/restrictive behaviors, and motor and cognitive behaviors that are all impaired in ASD. Cerebellar neuropathology including cerebellar hypoplasia and reduced cerebellar Purkinje cell numbers are the most consistent neuropathologies linked to ASD. The functional state of the cerebellum and its impact on brain function in ASD is the focus of this review. This review starts by recapitulating historical findings pointing towards an implication of the cerebellum, and to a lesser extent the basal ganglia structures, in TSA. We then detail the structure/function of the cerebellum at the regional and cellular levels before describing human and animal findings indicating a role of the cerebellum and basal ganglia in ASD. HUMAN AND ANIMAL FINDINGS: Several studies have attempted to identify the nature of the motor system dysfunction in ASD, and it became apparent that the motor fronto-striatal and cerebellar systems are major sites of dysfunction in this psychiatric illness. Anomalies in these structures have been revealed both at the anatomical and functional levels in human patients as well as in animal models. These models are obtained by manipulation of genes that are often implicated in glutamate transmission, by lesions of brain structures among which the cerebellum, by pharmacological treatment with drugs such as the Valproate or by maternal infections with bacterial membrane extracts of double stranded RNA mimicking a viral infection. CONCLUSION: The "cognitive approach" has dominated ASD research for three decades and led to the design of interventional strategies, which have yielded satisfactory results. Nevertheless, new approaches and alternative hypotheses on the aetiology and diagnosis of ASD are needed. Research focused on motor rather than psychiatric symptoms may have a greater potential to elucidate the neurobiological basis of ASD.

The negative bone effects of the disease and of chronic corticosteroid treatment in premenopausal women affected by rheumatoid arthritis.

Osteoporosis is a well-known extra-articular complication in rheumatoid arthritis (RA). The chronic corticosteroid treatment, the functional impairment associated with RA and the disease itself appear to be the most relevant determinants. Most of the previous studies involved postmenopausal women, in whom the estrogenic deficiency might amplify the negative effect towards bone of both RA and corticosteroid therapy. We decided to evaluate bone health in a cohort of premenopausal RA patients. The study population includes 47 premenopausal women attending our outpatient clinic for RA and twice as many healthy age-matched control women selected from the hospital personnel. The bone density at the spine and femoral neck were significantly lower in patients with RA as compared with controls. When spine bone mineral density (BMD) values were adjusted for the cumulative glucocorticoid (GC) dose alone and for the cumulative GC dose plus body mass index (BMI) the mean differences between two groups decreased but they remained statistically significant. We found no difference when the spine BMD was adjusted for cumulative GC dose, BMI and health assessment questionnaire. The difference in femoral neck BMD remained statistically significant also after all the same adjustments. In conclusion, our study shows that a BMD deficiency is frequent also in premenopausal women affected by RA, especially at femoral site and that the main determinants of this bone loss are not only the disease-related weight loss, corticosteroid therapy and functional impairment, but also the systemic effects of the disease itself.

Cell transplantation in the damaged adult brain.

Parkinson's disease (PD) is the most common movement disorder in Europe, affecting more than two million people between 50 and 70 years of age. The current therapeutic approaches are of symptomatic nature and fail to halt the progressive neurodegenerative course of the disease. The development of innovative and complementary approaches to promote cellular repair may pave the way for disease-modifying therapies which may lead to less suffering for the patients and their families and finally to more cost-effective therapies. To date, cell replacement trials in PD aiming at replacing lost dopamine neurons were mainly focused on placing the transplanted cells within the target site, the striatum, and not within the lesioned site, the substantia nigra (SN). This was based on the misconception that the adult brain constitutes a non-permissive barrier not allowing the outgrowth of long distance axons originating from transplanted embryonic neurons. A growing body of evidence is challenging this concept and proposing instead to place the graft within its ontogenic site. This has been performed in several lesional animal models for various traumatic or neurodegenerative pathologies of the brain. For instance, transplanted neurons within the lesioned motor cortex were shown to be able to send distant and appropriate projections to target areas including the spinal cord. Similarly, in an animal model of PD, mesencephalic embryonic cells transplanted within the lesioned SN send massive projections to the striatum and, to a lesser extent, the frontal cortex and the nucleus accumbens. This has lead to the proposal that homotopic transplantation may be an alternative in cell-based therapies as transplanted neurons can integrate within the host brain, send projections to target areas, restore the damaged circuitry, increase neurotransmitter levels and ameliorate behavior. We will discuss also the potential of replacing embryonic neuronal cells by stem cell derived neurons as the use of embryonic cells is not without an ethical and logistical burden; in this line many have thrived to derive neurons from embryonic stem cells (ESC) in order to use them for cell transplantation. These studies are already yielding important information for future approaches in the field of cell therapies in PD but also in other neurodegenerative disorders where cell transplantation therapy may be considered. While the field of cell replacement therapies has been recently called into question with contrasting results in transplanted PD patients, these new sets of findings are raising new hopes and opening new avenues in this rejuvenated field.

COVID-19 Vaccine Acceptance among Ajman Undergraduate Dental Students: A Cross-Sectional Study.

Background: Achieving widespread coronavirus disease 2019 (COVID-19) vaccination is crucial in controlling the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This cross-sectional study aimed to identify factors associated with the willingness of dental medicine students to receive the COVID-19 vaccine. Objectives: The study sought to assess the knowledge, attitudes, and behaviors of undergraduate dental students toward COVID-19 vaccines and to identify determinants, motivators, and barriers to vaccine uptake and booster receipt. Methods: A web-based survey was distributed to all 882 undergraduate dental surgery students in January 2022, and 70.7% of the students responded. The survey used χ2 tests and logistic regression analysis to examine the association among the variables. The significance level was set at α = 0.05. Results: Most participants (72.4%) reported having adequate knowledge of COVID-19. The vaccine acceptance rate was higher among male and older trainees, with no significant difference compared to women and younger trainees with no significant difference (p = 0.849). Acceptance of the vaccine varied according to study level (5-year program), ranging from 44.8% to 73.0%, in the following order 4th > 1st > 3rd > 5th > 2nd year. Social media (76.8%), government websites (66.5%), and family and friends (57.2%) were the main sources of COVID-19-related information. Among hesitant and unwilling participants, the main concerns were side effects (34.0%) and lack of understanding about the vaccine's mechanism (67.3%). Conclusions: Ajman dental students had moderate knowledge of COVID-19 and obtained information mainly from social media, government websites, and family and friends. Age, sex, and study year influenced vaccine acceptance. The main reasons for refusal were lack of knowledge, fear of side effects, and complications. Education campaigns are needed to increase vaccine acceptance among dental students.

Novel Coronavirus (COVID-19) Knowledge, Attitude, and Practice among Dental Sciences and Internship Students in Ajman University, United Arab Emirates: A Cross-Sectional Study.

Background: The aim of this study was to assess the COVID-19-related knowledge, attitudes, and practice among dental students (DS) and internship students at Ajman University (AU). Methods: A cross-sectional, web-based study was conducted among Ajman dental college students registered in the academic year 2019/2020, about COVID-19 during the first week of April 2020. A questionnaire was developed and distributed to all DS to examine their knowledge and attitudes toward the COVID-19 pandemic. Chi-square (χ2) test was used to investigate the level of association among categorical variables at the significance level of p < 0.05. Results: Out of 769 students in the dental college, majority (75%) had adequate knowledge of COVID-19, but only 40.6% of the participants projected a positive attitude. A positive behavior was reported by an overwhelming 94.5% of the participants. Participants above 25 years of age had significantly higher (p < 0.001) adequate knowledge (88.2%), positive attitude (56.9%), and positive behavior (100%) compared to those below 25 years of age. Study participants reported social media (71.1%), government websites (63.7%), and family and friends (41.0%) as top three sources of information regarding COVID-19 related information. Conclusion: The results of this study show that AU dental and internship students have adequate knowledge and positive attitude of the COVID-19 pandemic but the majority are not eager to adopt effective strategies to avoid the spread of COVID-19 (practice). Further education should be offered to encourage efficient infection management practices to protect students, faculty, and other university staff.

Patterns of adverse drug reactions in Jordan: a retrospective analysis of the National Pharmacovigilance Data Registry (2015-2021).

BACKGROUND: Post-marketing surveillance of drugs is a cornerstone of pharmacovigilance. This study was conducted to characterize patterns of adverse drug reactions (ADRs) reported in Jordan. RESEARCH DESIGN AND METHODS: ADR reports submitted to the pharmacovigilance database of the Jordan Food and Drug Administration during 2015-2021 were retrospectively analyzed. The most commonly reported drugs, drug classes, ADRs, and ADRs consequences were explored. Logistic regression identified possible predictors of reporting serious ADRs. RESULTS: A total of 2744 ADR reports were included, among which 28.4% were classified as serious. An annual increase in ADR reporting was observed. The most commonly implicated drug classes were antineoplastic and immunomodulating agents (24.0%), anti-infectives for systemic use (14.2%), and alimentary tract and metabolism (12.1%). Covid-19 vaccination was the most reported drug (22.8%). Fatigue (6.3%), injection site pain (6.1%), and headache (6.0%) were the top three common ADRs. Among ADRs with outcome information, 4.7% were fatal. Patient's age and intravenous medication use largely predicted reporting serious ADRs. CONCLUSIONS: This study provides contemporary insights into the post-marketing surveillance of drugs in Jordan. The findings are foundational for future studies exploring drug-ADRs causality relationships. Efforts that promote pharmacovigilance concepts should be sustained and enhanced at the national level.

An in vitro study of Ocimum sanctum as a chemotherapeutic agent on oral cancer cell-line.

Oral squamous cell carcinoma (OSCC) is the most commom cancer in the world. If remain untreated for several years, it may be fatal. Hence, it is important to prevent and treat OSCC at an early stage. In this study the effect of aqueous and dry leaves extract of Ocimum sanctum was observed on Ca9-22 cell line, which is an OSCC cell line. For this, Ca9-22 cell line was cultured and maintained. After 24 h, the cells were treated with aqueous and dry leaves extract of Ocimum sanctum plant. Viability of the cancerous cells were studied by 3-(4, 5-dimethythiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and neutral red uptake (NRU) assay. Minimum inhibitory concentrations (MIC), lethal concentration25 (LC25), lethal concentration50 (LC50) and highest permissive concentration (HPC) was calculated by probit computational method. Experimentally, the MIC value was 5 mg/L, whereas the HPC was 30 mg/L of the plant extract in aqueous state. For the dry extract the MIC was 5 mg/L whereas the HPC was 35 mg/L for both MTT and NRU assays. For MTT assay LC values: 7.41 (LC25), 14.79 (LC50) and 26.91 mg/L (LC75) for aqueous extract and 12.58 (LC25), 20.89 (LC50), 29.51 mg/L (LC75) for dry extract. For NRU assay LC values were 10.23 (LC25), 14.79 (LC50) and 20.89 mg/L (LC75) aqueous extract, and 16.59 (LC25), 23.44 (LC50), 30.19 mg/L (LC75) dry extract of the plant. From the above study it was concluded that, Ocimum sanctum have anti-cancerous activity. It can further be used for therapeutic purposes.

Anti-Cancer Activity of Curcumin on Multiple Myeloma.

Multiple Myeloma (MM) is the third most common and deadly hematological malignancy, which is characterized by a progressive monoclonal proliferation within the bone marrow. MM is cytogenetically heterogeneous with numerous genetic and epigenetic alterations, which lead to a wide spectrum of signaling pathways and cell cycle checkpoint aberrations. MM symptoms can be attributed to CRAB features (hyperCalcemia, Renal failure, Anemia, and Bone lesion), which profoundly affect both the Health-Related Quality of Life (HRQoL) and the life expectancy of patients. Despite all enhancement and improvement in therapeutic strategies, MM is almost incurable, and patients suffering from this disease eventually relapse. Curcumin is an active and non-toxic phenolic compound, isolated from the rhizome of Curcuma longa L. It has been widely studied and has a confirmed broad range of therapeutic properties, especially anti-cancer activity, and others, including anti-proliferation, anti-angiogenesis, antioxidant and anti-mutation activities. Curcumin induces apoptosis in cancerous cells and prevents Multidrug Resistance (MDR). Growing evidence concerning the therapeutic properties of curcumin caused a pharmacological impact on MM. It is confirmed that curcumin interferes with various signaling pathways and cell cycle checkpoints, and with oncogenes. In this paper, we summarized the anti- MM effects of curcumin.

Monitoring diclofenac adsorption by organophilic alkylpyridinium bentonites.

Organoclays have been applied as efficient adsorbents for pharmaceutical pollutants from aqueous solution. In this work, dodecylpyridinium chloride (C12pyCl) and hexadecylpyridinium chloride (C16pyCl) cationic surfactants were used for the preparation of organobentonites destined for diclofenac sodium (DFNa) adsorption, an anionic drug widely detected in wastewater. The organofunctionalization of the clay samples was performed under microwave irradiation at 50 °C for 5 min with surfactant amounts of 100% and 200% in relation to the cation exchange capacity (CEC) of the pristine bentonite. The amount of incorporated ammonium salts based on CHN elemental analysis was higher for all samples prepared with 200% of the CEC. The basal spacings of the organoclays ranged from 1.54 to 2.13 nm, indicating the entrance of organic cations into the interlayer spacing of the clay samples, and the spacing depended on the size of the alkyl organic chain. The hydrophobic character of the organobentonites was verified by thermogravimetry and infrared spectroscopy (FTIR). The adsorption isotherms showed that the drug capacity adsorption was influenced by the amount of surfactant incorporated into the bentonite, the packing density and the arrangement of the surfactants in the interlayer spacing. Zeta potential measurements of the organobentonites and FTIR analysis after drug adsorption suggested that electrostatic and nonelectrostatic interactions contributed to the mechanism of adsorption.

Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity.

The mechanism by which psychostimulants act as calming agents in humans with attention-deficit hyperactivity disorder (ADHD) or hyperkinetic disorder is currently unknown. Mice lacking the gene encoding the plasma membrane dopamine transporter (DAT) have elevated dopaminergic tone and are hyperactive. This activity was exacerbated by exposure to a novel environment. Additionally, these mice were impaired in spatial cognitive function, and they showed a decrease in locomotion in response to psychostimulants. This paradoxical calming effect of psychostimulants depended on serotonergic neurotransmission. The parallels between the DAT knockout mice and individuals with ADHD suggest that common mechanisms may underlie some of their behaviors and responses to psychostimulants.

Anterior pituitary hypoplasia and dwarfism in mice lacking the dopamine transporter.

Deletion of the dopamine transporter (DAT) results in increased dopaminergic tone, anterior pituitary hypoplasia, dwarfism, and an inability to lactate. DAT elimination alters the spatial distribution and dramatically reduces the numbers of lactotrophs and somatotrophs in the pituitary. Despite having normal circulating levels of growth hormone and prolactin in blood, hypoplastic glands from DAT-/- mice fail to respond to secretagog stimulation. The effects of DAT deletion on pituitary function result from elevated DA levels that down-regulate the lactotroph D2 DA receptors and depress hypothalamic growth hormone-releasing hormone content. These results reveal an unexpected and important role or DA in the control of developmental events in the pituitary gland and assign a critical role for hypothalamic DA reuptake in regulating these events.

Clinical review of the management of fulminant clostridium difficile infection.

BACKGROUND: Clostridium difficile infection (CDI) is a frequent cause of morbidity and mortality among elderly hospitalized patients. A small but increasing number of patients have developed fulminant CDI, and a significant number of these patients require emergency colectomy. In this review, we discuss the risk factors, pathophysiology, diagnosis, and management of fulminant CDI. DATA SOURCES: A literature search (Medline, Embase, Cochrane Library, Biosis, Science Citation Index, Ovid Journals) was performed from the period between January 1980 and June 2008 using the key words "Clostridium difficile,""pseudomembranous enterocolitis,""colectomy,""acute abdomen,""antibiotic-associated diarrhea," or "fulminant Clostridium difficile colitis." Articles not in English or not related to human subjects were excluded. For this review, we analyzed the articles identified in our original search and those articles cited in the original review articles. No randomized trials were found on the surgical management of fulminant CDI and only retrospective studies with a minimum of five patients were used in the review. With respect to medical treatment, we based our review on guideline articles, systematic reviews, and available randomized trials. CONCLUSION: Both the incidence and severity of CDI are increasing. Fulminant CDI is underappreciated as a life-threatening disease because of a lack of awareness of its severity and its nonspecific clinical syndrome. Early diagnosis and treatment are essential for a good outcome, and early surgical intervention should be used in patients who are unresponsive to medical therapy. The surgical procedure of choice is a total abdominal colectomy with end ileostomy, although the mortality rate remains high.

Cyanobacterial formation of intracellular Ca-carbonates in undersaturated solutions.

Cyanobacteria have long been thought to induce the formation of Ca-carbonates as secondary by-products of their metabolic activity, by shifting the chemical composition of their extracellular environment to conditions favoring mineral precipitation. Some cyanobacterial species forming Ca-carbonates intracellularly were recently discovered. However, the environmental conditions under which this intracellular biomineralization process can occur and the impact of cyanobacterial species forming Ca-carbonates intracellularly on extracellular carbonatogenesis are not known. Here, we show that these cyanobacteria can form Ca-carbonates intracellularly while growing in extracellular solutions undersaturated with respect to all Ca-carbonate phases, that is, conditions thermodynamically unfavorable to mineral precipitation. This shows that intracellular Ca-carbonate biomineralization is an active process; that is, it costs energy provided by the cells. The cost of energy may be due to the active accumulation of Ca intracellularly. Moreover, unlike cyanobacterial strains that have been usually considered before by studies on Ca-carbonate biomineralization, cyanobacteria forming intracellular carbonates may slow down or hamper extracellular carbonatogenesis, by decreasing the saturation index of their extracellular solution following the buffering of the concentration of extracellular calcium to low levels.

Cocaine-induced sensitization is associated with altered dynamics of transcriptional responses of the dopamine transporter, tyrosine hydroxylase, and dopamine D2 receptors in C57Bl/6J mice.

RATIONALE: Behavioural sensitization is a long lasting phenomenon that has been proposed to be involved in drug addiction. Although the expression of cocaine-induced sensitization has been associated with the activity of the mesencephalic dopaminergic neurons, little is known about the transcriptional adaptations of these neurons to a new challenge with cocaine long after cessation of repeated exposure to the drug. OBJECTIVES: We studied the time course of the mRNA levels of three main regulatory elements of dopaminergic transmission after a challenge with cocaine (15 mg/kg) that followed 21 days of withdrawal from a cocaine pretreatment (20 mg/kg, ip, every 2 days for 21 days) in C57Bl/6J mice. MATERIALS AND METHODS: Mice were placed 45 min in activity chambers and were killed 45 min, 2 h or 24 h after the challenge injection. Dopamine transporter (DAT), D2 auto-receptor (D2) and tyrosine hydroxylase (TH) mRNA levels were assessed by in situ hybridization in the ventral tegmental area and the substantia nigra compacta. RESULTS: As compared to vehicle challenge, cocaine challenge in vehicle pretreated mice induced a rapid increase (+208%) in DAT mRNA (45 min) followed by a delayed decrease (-70%) (24 h), while TH and D2 mRNA were both increased (+45%) 24 h after the challenge. In cocaine pretreated mice, cocaine-induced short-term increase and long-term decrease in DAT mRNA levels were amplified (+328%) and reduced (-40%), respectively. CONCLUSIONS: Repeated exposure to cocaine alters the transcriptional response of DA neurons to a new cocaine challenge long after cessation of repeated exposure to the drug. They point to the DAT mRNA as a major responsive element to a new presentation of cocaine.

Green nanocomposites: synthesis and characterization.

A series of intercalated and exfoliated nanocomposites montmorillonite-ulvan was prepared. Ulvan, extracted from the green algae, is a water-soluble polysaccharide biopolymer. Depending on the drying process, air or freeze drying, ulvan were inserted in the interlayer space or adsorbed on the both sides of inorganic layers. The crystallization of water molecules bounded to the ulvan induced the delamination of the layers during the lyophilization. Thermogravimetric experiments show a high percentage (approximately 51%) of organic matter for the freeze dried samples and a lowest one (approximately 17%) for the air dried solids. X-Ray Diffraction patterns exhibit a d(001) varying with the content of organic matter. When the delamination occurs, the (001) reflection disappears. Transmission electron microscopy micrographs show individual layers for the highest amount of ulvan.

Gene expression regulation following behavioral sensitization to cocaine in transgenic mice lacking the glucocorticoid receptor in the brain.

Several findings suggest that glucocorticoid hormones influence the propensity of an individual to develop cocaine abuse. These hormones activate two related transcription factors, the glucocorticoid receptor and the mineralocorticoid receptor. We have shown previously that mice carrying a mutation of the glucocorticoid receptor gene specifically in neural cells, glucocorticoid receptor knock-out in the brain, show a dramatic decrease in cocaine-induced self-administration and no behavioral sensitization to this drug, two experimental procedures considered relevant models of addiction. Here, we investigated in glucocorticoid receptor knock-out in the brain mice the consequences of this mutation at the level of the expression of neuropeptide, dopamine receptor and glutamate receptor subunit mRNAs. We quantified mRNA levels in the cortex, striatum and accumbens under basal conditions and following acute or repeated cocaine treatments. Our results show that, under basal conditions, neuropeptide (substance P, dynorphin) and dopamine receptor (D1, D2) mRNAs were decreased in glucocorticoid receptor knock-out in the brain mice in the dorsal striatum but not in the accumbens. However, cocaine-induced changes in the levels of these mRNAs were not modified in glucocorticoid receptor knock-out in the brain mice. In contrast, mutant mice showed altered response in mRNA levels of N-methyl-D-aspartate, GLUR5 and GLUR6 glutamate receptor subunits as well as of enkephalin following cocaine administration. These modifications may be associated to decrease of behavioral effects of cocaine observed in glucocorticoid receptor knock-out in the brain mice.

Intraoral minor salivary gland tumors: a review of 75 cases in a Libyan population.

Minor salivary gland carcinomas are uncommon but most often occur in the oral cavity, particularly the hard palate. Dental examination may provide an opportunity for early detection. During the period of 1977-2000 a group of 75 patients (31 males and 44 females, median age 44.2 years and range 15-86 years) with minor salivary gland tumors were diagnosed, based on the 1991 WHO classification. The peak occurrence of the tumors was in the fifth decade for males and sixth decade for females. The frequency of benign tumors was 38.6% (n = 29) and malignant tumors 61.3% (n = 46). Pleomorphic adenoma was the most common histological type of benign tumor identified whereas mucoepidermoid carcinoma and adenoid cystic carcinoma were the most common malignant tumors. The most common primary location of the tumors was the palate followed by the cheek. A benign tumor usually presented as an asymptomatic swelling and ulceration, pain being more frequently associated with the malignant tumors. This study shows that intraoral tumors of minor salivary glands vary widely in presentation, and should be taking into account by medical and dental practitioners in any differential diagnosis when assessing intraoral pathology. Any lesion arising from the hard palate (the most common site in this series) should be considered as a possible minor salivary gland tumor. Referral to a multidisciplinary head and neck clinic following diagnosis is strongly recommended.

Protease-activated receptors (PARs) in cancer: Novel biased signaling and targets for therapy.

Despite the fact that G protein-coupled receptors (GPCRs) mediate numerous physiological processes and represent targets for therapeutics for a vast array of diseases, their role in tumor biology is under appreciated. Protease-activated receptors (PARs) form a family which belongs to GPCR class A. PAR1&2 emerge with a central role in epithelial malignancies. Although the part of PAR1&2 in cancer is on the rise, their underlying signaling events are poorly understood. We review hereby past, present, and future cancer-associated PAR biology. Mainly, their role in physiological (placenta-cytotophobalst) and patho-physiological invasion processes. The identification and characterization of signal pleckstrin homology (PH)-domain-binding motifs established critical sites for breast cancer growth in PAR1&2. Among the proteins found to harbor important PH-domains and are involved in PAR biology are Akt/PKB as also Etk/Bmx and Vav3. A point mutation in PAR2, H349A, but not R352A, abrogated PH-protein association and is sufficient to markedly reduce PAR2-instigated breast tumor growth in vivo as also placental extravillous trophoblast (EVT) invasion in vitro is markedly reduced. Similarly, the PAR1 mutant hPar1-7A, which is unable to bind PH-domain, inhibits mammary tumors and EVT invasion, endowing these motifs with physiological significance and underscoring the importance of these previously unknown PAR1 and PAR2 PH-domain-binding motifs in both pathological and physiological invasion processes.

Silylation of leached-vermiculites following reaction with imidazole and copper sorption behavior.

Organically modified vermiculites were synthesized by previous silylation of three leached vermiculites, V0.3Cl, V0.5Cl and V0.8Cl, under anhydrous conditions following reaction with imidazole (Im), which acted as chelating agent for copper retention. Elemental analysis, X-ray diffraction, infrared spectroscopy, scanning electronic microscopy, transmission electron microscopy, (29)Si and (13)C NMR and nitrogen adsorption/desorption measurements were used to characterize pristine, leached and organofunctionalized solids. X-ray photoelectron spectroscopy (XPS) was used to evaluate the surface after copper sorption. Parameters such as contact time, pH and initial cation concentration for the adsorption of Cu(II) ions were investigated. The adsorption equilibrium data were fitted using the Langmuir isotherm model and the monolayer adsorption capacities were 2.38, 2.52 and 2.69mmolg(-1) for V0.5Cl-Im, V0.3Cl-Im and V0.8Cl-Im, respectively, at pH 6.0 and 298K for a time reaction of 80min. The sorption rates were described by pseudo-second-order kinetics. The chloropropyl imidazole vermiculites are promising adsorbents for the rapid removal of Cu(II) ions from aqueous solution.