Role of Memantine in Limiting Cochleotoxicity in Rats.

Οur aim was to test whether amikacin's well-known cochleotoxic effects could be suppressed, depending on whether an NMDA-antagonist (memantine) was administered simultaneously with or after amikacin treatment. Forty Wistar rats were used in this experiment. Ten rats acted as controls and received no medication (group A). Amikacin (200 mg/kg) was administered intraperitoneally (i.p.) once daily for 14 days to 10 animals in group B; amikacin (200 mg/kg) was administered concurrently with memantine (10 mg/kg, i.p., once daily) to the same 10 animals in group C. Group D was given intraperitoneal memantine (10 mg/kg, once daily) for 14 days following a 2-week amikacin treatment. The cochlear activity of the right ear was tested using DPOAE in conscious animals. All animals were sacrificed at the conclusion of the experiment and both cochleae were collected for histological and immunohistochemical analysis. All groups treated with amikacin showed decreased cochlear activity, as testified by decreased DPOAE-amplitudes compared to the pre-treatment state. In the rats of group B, the DPOAE reduction was more pronounced. On histologic exam, the cochlear structures of group C rats and, although to a lesser extent, group D rats showed less severe cochlea damage. Memantine plays a protective role, resulting in restoring partially cochlear structures when administered either simultaneously with or after completion of amikacin i.p. treatment in rats.

The Effect of Isotretinoin on Insulin Resistance and Serum Adiponectin Levels in Acne Vulgaris Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Isotretinoin is the drug of choice for severe acne. We sought to examine the potential link between isotretinoin and insulin resistance. METHODS: We conducted a systematic review and meta-analysis in accordance with the PRISMA statement. A comprehensive search of the PubMed/MEDLINE, SCOPUS, and Cochrane databases was performed until 12 January 2022 utilizing the PICO (Patient, Intervention, Comparison, Outcome) tool. Fifteen English-language studies focusing on isotretinoin-treated acne patients were included. Serum levels of insulin, glucose, and adiponectin were evaluated before and after treatment, and insulin sensitivity was assessed using the HOMA-IR. A meta-analysis was conducted using RevMan 5.4.1 software, and a quality assessment was undertaken using the ROBINS-I tool. RESULTS: The meta-analysis unveiled a statistically significant rise in the post-treatment levels of adiponectin, an anti-inflammatory agent, which inhibits liver glucose production while enhancing insulin sensitivity (SMD = 0.86; 95% confidence interval (95% CI) = 0.48-1.25, p-value < 0.0001; I2 = 58%). Our subgroup analysis based on study type yielded consistent findings. However, no statistically significant outcomes were observed for insulin, glucose levels, and the HOMA-IR. CONCLUSIONS: There is not a clear association between isotretinoin and insulin resistance, but it appears to enhance the serum levels of adiponectin, which participates in glucose metabolism.

Gestational Diabetes Mellitus and Its Correlation in the Development of Pancreatic Cancer: A 10-Year Systematic Review.

PURPOSE: Pancreatic cancer (PC) is a fatal malignancy with an aggressive course derived from the cells of pancreatic tissue. Gestational diabetes mellitus (GDM) is a state of spontaneous hyperglycemia occurring during gestation and has been suggested as a risk factor PC. Women with a history of GDM revealed a risk rate of 7.1% for the development of PC. The current systematic review aims to investigate the correlation between GDM and the degree to the prevalence of PC. METHODOLOGY: For this systematic review, the PICO model was prepared to construct and outline the exact questions of the study, a PRISMA flow diagram was prepared and quality assessment was conducted using the Newcastle Ottawa Scale (NOS) for Cohort Studies, the NIH Quality Assessment Tool-Criteria for Case Reports and the Cochrane quality assessment tool for Systematic Reviews and Meta-analysis studies. RESULT: A total of eight articles were retrieved from the main databases, and a table was created to summarize the information found. Even though the data found were limited, the quality assessment performed revealed that the articles were of high validity. CONCLUSIONS: It can be concluded that GDM has an association with the development of PC and can be considered as a risk factor.

Genetic and Epigenetic Factors Associated with Postpartum Psychosis: A 5-Year Systematic Review.

Purpose: Postpartum psychosis (PPP) is a serious mental health illness affecting women post-parturition. Around 1 in 1000 women are affected by postpartum psychosis, and the symptoms usually appear within 2 weeks after birth. Postpartum mental disorders are classified into 3 main categories starting from the least to most severe types, including baby blues, postpartum depression, and postpartum psychosis. Materials and Methods: In this systematic review, genetic and epigenetic factors associated with postpartum psychosis are discussed. A PRISMA flow diagram was followed, and the following databases were used as main sources: PubMed, ScienceDirect, and Scopus. Additional information was retrieved from external sources and organizations. The time period for the articles extracted was 5 years. Results: Initially, a total of 2379 articled were found. After the stated criteria were applied, 58 articles were identified along with 20 articles from additional sources, which were then narrowed down to a final total of 29 articles. Conclusions: It can be concluded that there is an association between PPP and genetic and epigenetic risk factors. However, based on the data retrieved and examined, the association was found to be greater for genetic factors. Additionally, the presence of bipolar disorder and disruption of the circadian cycle played a crucial role in the development of PPP.

Carbapenem-resistant Klebsiella pneumoniae in the Balkans: Clonal distribution and associated resistance determinants.

Carbapenems are considered to be among the last line antibiotics against extended-spectrum ß-lactamase producing Enterobacterales. Carbapenem-resistant Klebsiella pneumoniae (CRKP) has been frequently reported and its spread in Europe is indisputable and poses an enormous threat to hospitalized patients which is of growing concern. This review aims to record prevalence of CRKP in the Balkan region and to review the current knowledge about this life-threatening pathogen. In this review, we summarize data about clinical isolates of carbapenem-resistant K. pneumoniae from Greece, Croatia, Romania, Bulgaria, Serbia, Slovenia, Montenegro, Bosnia-Herzegovina and Albania from published reports between 2000 and 2023. Among Balkan countries, Greece and Romania are the ones with the most reports about CRKP. Since 2007, KPCs are the dominant carbapenemases in both countries. KPC-2 and NDM-1-producing K. pneumoniae strains have been identified as the most frequent CRKP in Croatia, Bulgaria, Serbia, and Slovenia. OXA-48 enzyme has been identified in most Balkan countries. In addition, since 2018, CRKP sequence type 11 (ST11) seems to have replaced ST258 in Balkan Peninsula, while ST15 continues to thrive throughout the years. Not only efficacy of colistin against CRKP has decreased dramatically during the last ten years but colistin resistance mechanism is based on alterations of chromosomal mgrB gene, rather than the already known mcr genes.Moreover, ceftazidime-avibactam-resistant CRKP were detected mostly in Greece. Emergence of CRKP poses a severe threat to the Balkan countries. Due to the narrow therapeutic window, it is essential to prevent the spread of multiresistant K. pneumoniae strains.

Stress, Anxiety, and Depression Levels among University Students: Three Years from the Beginning of the Pandemic.

BACKGROUND: Three years after the outbreak of the COVID-19 pandemic, psychological distress among college students remains increased. This study assesses stress, anxiety, and depression levels among students of the Aristotle University of Thessaloniki by the end of the third year of the pandemic (November 2022), revealing demographic characteristics and probable stressors. METHODS: A questionnaire was distributed in November 2022 via the academic students' e-mails. The evaluation was performed with the DASS21 survey tool. The correlation analysis and the effect size calculation were performed with the t-test. RESULTS: The majority of participants were undergraduates, on their first or second academic year, female students (67%), age of 18 to 21, unmarried or single (91%), and vaccinated against COVID-19 infection (83.4%). Severely increased levels of stress, anxiety, and depression (21.3%, 23.3%, and 25.1%, respectively) were measured. The normal and mild levels of stress, anxiety, and depression were 64.0%, 66.5%, and 57.2%, respectively. Female and younger students were at a higher risk of extremely severe stress, anxiety and depression prevalence (ORs up to 2.07, p-Values < 0.00001). Participants who were receiving psychological or psychiatric treatment exhibited severe stress, anxiety, and depression levels (ORs above 2.9, p-Values < 0.00001). CONCLUSIONS: Despite the undeniable withdrawal of the COVID-19 pandemic, the community of the Aristotle University of Thessaloniki presents high stress, anxiety, and depression levels, similar to those reported during the first year of the pandemic (November 2020). Stressors and risk factors were according to the reported literature and previous studies on Greek students. Academic psychological support offices should consider the students' "profile" in order to evaluate properly the potential risk for emotional and psychological distress. Evidence suggest that new technology (virtual reality, tele-psychiatry or tele-support apps and sessions) should also be implemented in universities.

Immunohistochemical study of MMP-2, MMP-9, EGFR and IL-8 in decidual and trophoblastic specimens of recurrent pregnancy loss cases.

BACKGROUND AND AIM: Unexplained recurrent pregnancy loss has been a a challenging research task to experts since there is no explicit pathophysiological mechanism and therefore, the treatment remains elusive. Immunological imbalance and morphological abnormalities are under investigation. This study aims to evaluate the implication of MMP-2, MMP-9, EGFR, and IL-8 in recurrent pregnancy loss cases. MATERIALS & METHODS: The study was carried out through comparison among two groups; the unexplained miscarriage group which consisted of 22 women, and the control group consisted of 18 women, who had electively terminated their pregnancies. Both groups were in the first trimester of gestation. The specimens included the trophoblast, decidua basalis, and decidua parietalis. The study was conducted via immunohistochemical methods. Antibodies were used against MMP-2, MMP-9, EGFR, and IL-8. The results were presented at a contingency table and were statistically analyzed with the Chi-Square Test (X2). RESULTS: There were remarkable disparities in some cases in the comparison of the two groups. MMP-9 was detected significantly high in recurrent pregnancy loss (RPL) cases, both on trophoblastic and decidual specimens (p-value < .00001), MMP-2 displayed no difference among the two groups (mild to moderate detection on trophoblast and almost negative on decidual tissues). EGFR was highly detected in trophoblastic tissue (p-value = .014). IL-8 detection was particularly different in both trophoblast and decidua parietalis of the two groups (p-value < .01). CONCLUSION: The study revealed both morphological and immunological dysregulations that might participate in the RPL pathogenesis.

The Effect of Electromagnetic Radiation Transmitted from Routers on Antibiotic Susceptibility of Bacterial Pathogens.

Background: Electromagnetic non-ionizing radiation has both thermal and non-thermal outcomes on biological systems, such as humans, animals, and bacteria. Objective: This study aimed to investigate the effect of non-ionizing radiofrequency radiation, emitted by Wi-Fi routers, on bacterial strains and the modification of their susceptibility to modern antibiotics. Material and Methods: In this case-control paired study, four bacteria were selected, and one colony from each bacterial strain was exposed to Wi-Fi radiation forming the exposure group. Another set of colonies was not exposed to Wi-Fi radiation, forming the control group. Eight different antibiotic disks were set on the bacterial plates, and the inhibition zone was measured every 3 h for each colony. Results: Electromagnetic radiation affects bacterial colonies and their susceptibility to antibiotics. Analysis revealed statistically significant differences, correlated with the bacterial strain, the antibiotic agent, and the time of the exposure, in the inhibition zones, mostly after 6 and 24 h (p-value < 0.05). Conclusion: A correlation was observed between antibiotic susceptibility and non-ionizing radiofrequency exposure. Studying the effects of radiofrequency radiation on prokaryotic organisms could clarify more complicated cell structures and organisms, such as eukaryotic. Further experiments, in vitro and in vivo, could provide more information about these outcomes and cause experts to discuss the current guidelines of exposure limits.

The Effects of Intravitreal Administration of Antifungal Drugs on the Structure and Mechanical Properties Peripheral Blood Erythrocyte Surface in Rabbits.

BACKGROUND: Fungal infections can pose great threat to sight. Immediate treatment is usually required; antifungal agents are widely accepted and are effective in most cases. The present experimental study aims to investigate the probable effects of intravitreal injection of antifungal agents on the structure and mechanical properties of the surface of peripheral blood erythrocytes. METHODS: Nine albino New Zealand white rabbits, aged five months old, were chosen for the experiment. Solutions of micafungin, voriconazole, or balanced salt solution (BSS) were injected into the midvitreous. Animals were divided into two experimental groups and one control group. Blood sampling from an intravenous (IV) line was performed after 10 days from the last IV injection. An atomic force microscope (AFM) was used to study the structural and mechanical properties of cell surfaces. RESULTS: The analysis results showed that the parameters of the cytoskeleton's spatial organization changed insignificantly with the antifungal drug treatment. CONCLUSIONS: Our findings suggest that locally administered antifungal drugs can cause significant changes to the structure and frictional properties of the erythrocyte surface. These effects occur in the long-term period after administration of the drugs and represent a potential possibility for violation of blood supply to tissues, and the further development of negative side effects.

Cataract Surgery during the COVID-19 Pandemic: Insights from a Greek Tertiary Hospital.

BACKGROUND: COVID-19 has affected everyday clinical practice, having an impact on the quality of healthcare provided, even in eye clinic departments. The aim of this study is to evaluate the consequences of this worldwide pandemic on cataract surgery in a Greek tertiary university hospital. METHODS: A total of 805 patients were included in this study. The number of cataract surgeries (CS), the type, the unilateral or bilateral appearance as well as the stage of cataract were recorded for the months between January and June 2019 (pre-COVID period) and compared with the same period in 2021 (during the pandemic outbreak) in the Department of Ophthalmology of Thessaloniki General Hospital G. Papanikolaou. RESULTS: A significant reduction in the number of CS as well as a significant increase in advanced and/or bilateral cataracts in 2021 compared to the pre-COVID period were observed. CONCLUSION: The COVID-19 pandemic has affected equally the value of ophthalmic interventions as well as the patients' quality of life, being a powerful reminder of the significant physical and psychological benefits of CS, especially for older adults and patients with comorbidities.

Stress, Anxiety and Depression Prevalence among Greek University Students during COVID-19 Pandemic: A Two-Year Survey.

Background: The negative effect of COVID-19 pandemic on college students' mental health is well-demonstrated. The aim of this study is to assess the impact of the pandemic on the students of Aristotle University of Thessaloniki (Northern Greece), in terms of stress, anxiety, and depression, and to analyze the probable correlation of various social and phycological factors. Methods: The survey was conducted in the form of a questionnaire, which was first distributed in November 2020 and then re-launched in November 2021. The evaluation was carried out through the DASS21 screening tool. Associations regarding participants' characteristics and the three variables (stress, anxiety, and depression) were investigated with Pearson's chi-squared (Χ2) test. Results: The first-year results (November 2020) revealed severe prevalence of stress, anxiety, and depression (37.4%, 27.2% and 47% respectively). The second-year results (November 2021) revealed a significant augmentation in all three variables, mainly for the extreme severe scales (47.3%, 41.1% and 55% respectively). Participants who were receiving psychiatric treatment exhibited higher levels of stress, anxiety, and depression, especially during the second year of the pandemic (p-Value < 0.00001). Female students' mental health was at higher risk, as elevated prevalence of negative symptoms was observed (p-Value < 0.00001). Conclusions: The community of Aristotle University of Thessaloniki has been greatly affected during the last 2 years. The inherent risks of the confinement measures on students' well-being and mental health are undeniable. Recurrent annual psychological evaluation in universities and colleges is strongly advised.

Renal Injuries after Cardiac Arrest: A Morphological Ultrastructural Study.

BACKGROUND: This study aims to investigate the probable lesions and injuries induced in the renal tissue after a cardiac arrest. The renal ischemia-reperfusion model in cardiac arrest describes the effects of ischemia in the kidneys, alongside a whole-body ischemia-reperfusion injury. This protocol excludes ischemic conditions caused by surgical vascular manipulation, venous injury or venous congestion. METHODS: For the experimental study, 24 swine were subjected to cardiac arrest. Seven minutes later, the cardiopulmonary resuscitation technique was performed for 5 min. Afterwards, advanced life support was provided. The resuscitated swine consisted one group and the non-resuscitated the other. Tissue samples were obtained from both groups for light and electron microscopy evaluation. RESULTS: Tissue lesions were observed in the tubules, parallel to destruction of the microvilli, reduction in the basal membrane invaginations, enlarged mitochondria, cellular vacuolization, cellular apoptosis and disorganization. In addition, fusion of the podocytes, destruction of the Bowman's capsule parietal epithelium and abnormal peripheral urinary space was observed. The damage appeared more extensive in the non-resuscitated swine group. CONCLUSIONS: Acute kidney injury is not the leading cause of death after cardiac arrest. However, evidence suggests that the kidney damage after a cardiac arrest should be highly considered in the prognosis of the patients' health outcome.

Management of Harlequin Ichthyosis: A Brief Review of the Recent Literature.

Harlequin ichthyosis (HI) is a life-threatening genetic disorder that largely affects the skin of infants. HI is the most severe form of the autosomal recessive disorder known as ichthyosis. It is caused by mutations in the A12 cassette (lipid-transporter adenosine triphosphate-binding cassette A12). Neonates affected by this disease are born with specific morphological characteristics, the most prominent of which is the appearance of platelet keratotic scales separated by erythematous fissures. The facial features include eclabium, ectropion, a distinct flattened nose, and dysplastic ears. A common finding among those with HI is impaired skin barrier function. The purpose of the present narrative review is to assess the most recent literature regarding the management of HI. Emphasis is given to surgical management and consultation, to the indications for timing and surgical intervention, to the risks that are presented with surgery, and to the details of the surgical procedure itself. Management of HI requires a multidisciplinary team of experts, and specific guidelines are needed in order for the risks to be minimized and viability to be increased.

Antidiabetic Drugs in the Treatment of Alzheimer's Disease.

The public health burden of type 2 diabetes mellitus and Alzheimer's disease is steadily increasing worldwide, especially in the population of older adults. Epidemiological and clinical studies suggest a possible shared pathophysiology between the two diseases and an increased risk of AD in patients with type 2 diabetes mellitus. Therefore, in recent years, there has been a substantial interest in identifying the mechanisms of action of antidiabetic drugs and their potential use in Alzheimer's disease. Human studies in patients with mild cognitive impairment and Alzheimer's disease have shown that administration of some antidiabetic medications, such as intranasal insulin, metformin, incretins, and thiazolidinediones, can improve cognition and memory. This review aims to examine the latest evidence on antidiabetic medications as a potential candidate for the treatment of Alzheimer's disease.

Immunohistochemical Evaluation of CD3, CD4, CD8, and CD20 in Decidual and Trophoblastic Tissue Specimens of Patients with Recurrent Pregnancy Loss.

Recurrent miscarriages affect up to 5% of couples. CD3+ (T-lymphocytes), CD4+ (helper T-lymphocytes), CD8+ (cytotoxic T-lymphocytes), and CD20+ (B-lymphocytes) cells may participate in the pathophysiology of recurrent pregnancy loss (RPL). The aim of this study was to investigate the complicity of these molecules in RPL. The experimental specimens were obtained from 20 females who underwent miscarriages in the first gestational trimester, while the control group's specimens consisted of 20 females who proceeded with voluntary pregnancy termination during the same period. Tissue samples were taken from the decidua basalis, decidua parietalis, and trophoblast (placental chorionic villi) and were studied using immunohistochemical methods. Monoclonal antibodies were used against CD3, CD4, CD8, and CD20 cells. The lymphocyte levels in the decidua parietalis displayed profound disparities among the two groups. The decidua basalis and trophoblast exhibited almost the same disparities regarding positive CD cells. The comparison of CD4+ and CD8+ cells in the endometrial tissue revealed a significant difference between the two groups of study. The analysis uncovered a strong relationship between RPL and the presence of CD3+, CD4+, CD8+, and CD20+ cells in the decidua parietalis tissue. The number of positive T cells was decreased in the decidual basalis and chorionic villi, proving that their absence significantly disrupts the balance of the immunological environment.

Psychological Distress in Primary Healthcare Workers during the COVID-19 Pandemic in Greece.

OBJECTIVE: The present study aims to evaluate the symptoms of psychological distress during the COVID-19 pandemic, in Greek primary healthcare workers, correlating them with their individual characteristics. MATERIALS AND METHODS: The research is based on a self-report questionnaire distributed to primary HCWs of Thessaloniki's public health care units. A sample of 143 respondents was gathered. The questionnaire consists of 21 items: 6 demographic questions, 9 on personal distress, 5 on work-related distress and 1 on one dominant feeling of the participants. These items were based on existing validated measures, such as the "Depression Anxiety Stress Scale-21", the "Kessler Psychological Distress Scale-10", "General Health Questionnaire- 28" and "Hospital Anxiety and Depression Scale". The associations between participants' gender, education, specialty and parenthood were determined with Pearson's chi-squared (χ2) test. RESULTS: Overall, 70.4% of HCWs were generally affected by the pandemic. The personal distress factors revealed that the majority (67%) experienced distress due to routine changes. The effects on health behavior (sleep, eating behavior and substance use) were not high. Psychological/psychiatric needs were relatively low, while negative emotions and need of social support were high. 31.4% displayed intense emotional instability. All work-related distress factors were rated high. Worry about contracting COVID-19 in the workplace scored the highest (82.6%). Almost half of the participants felt exposed to COVID-19 infection (47.0%). Anxiety (47.2%) and burn-out (78.4%) symptoms were also revealed. Female participants appeared to be more anxious (P<0.01) and upset (P=0.013). CONCLUSION: The exposure to a constant risk could potentially lead to an increase in HCWs' psychological distress. Designing the right tools and organizing the right plans are of paramount importance to prevent the deterioration of their wellness and quality of life.

Diagnosis and Staging of Pediatric Non-Alcoholic Fatty Liver Disease: Is Classical Ultrasound the Answer?

The increased prevalence of non-alcoholic fatty liver disease (NAFLD) requires special attention in pediatric patients, as it manifests in them in a more severe and progressive way compared to adults. The implementation of the appropriate therapeutic interventions is determinant of the attempts to treat it. For that purpose, early diagnosis and staging of the disease is essential. The purpose of this review was to find and reveal the most appropriate diagnostic strategies and tools for diagnosis and staging of pediatric NAFLD/NASH based on their accuracy, safety and effectiveness. The methodology followed was that of the literature review. Particular emphasis was put on the recent bibliography. A comparative study of published articles about the diagnosis and management of pediatric NAFLD/NASH was also performed. In terms of diagnosis, the findings converged on the use of classical ultrasound. Ultrasound presented average sensitivity and specificity for diagnosing the disease in children, while in the adult population, sensitivity and specificity were significantly higher. Proton density fat fraction magnetic resonance imaging has been increasingly used for the diagnosis of steatosis in pediatric patients. Elastography is an effective tool for staging liver fibrosis and discriminating NASH from NAFLD in children. Even though liver biopsy is the gold standard, especially for NASH, it should be avoided for pediatric patients. Biochemical tests are less specific and less sensitive for the diagnosis of NAFLD, and some of them are of high cost. It seems that diagnostic imaging should be a first-line tool for the staging and monitoring pediatric NAFLD/NASH in order for appropriate interventions to be implanted in a timely way.

mcr Genes Conferring Colistin Resistance in Enterobacterales; a Five Year Overview.

The present review aims to study and detect the global emergence of mcr genes in E. coli, K. pneumoniae and Salmonella spp., isolates from human specimens over the last six years. Nowadays the rise of multidrug-resistant superbugs has made essential the return of drugs that were previously abandoned. A clear example is colistin, which acts against multidrug - resistant gram - negative pathogens, including Enterobacterales. Colistin resistance is an unfortunate fact, with the emergence of mcr genes conferring resistance to colistin in Enterobacterales posing the most recent threat. Literature about mcr genes and their spread in E. coli, K. pneumoniae and Salmonella spp. is cited, focusing on the emergence of mcr genes in human specimens since 2015. The data were taken from the PubMed and Scopus databases. It seems that the mcr-1 gene continues to be the protagonist among the three species. E. coli is the dominant species harbouring mcr genes. Moreover, plasmid - mediated colistin resistance is also conferred upon other species that carry different genes resistant to antibiotics. There are only scarse reports on human Salmonella spp isolates harbouring mcr genes. Finally, the emergence of the mcr-9 gene in all of them is quite remarkable. CONCLUSION: Plasmid - mediated colistin resistance in Enterobacterales is a global issue and has been worsening over the years. The continuous mutations of mcr gene subtypes underline the need for better surveillance, constant investigation and wise use of colistin, especially in countries with high levels of antibiotic resistance.

In Utero Exposure to Antihypertensive Medication during the First Trimester: Is the Risk Worth Taking?

The aim of this study is to evaluate and present the evidence so far, regarding fetal outcomes after in utero exposure to antihypertensive medication. Hypertensive disorders during pregnancy constitute a significant risk factor for maternal and fetal outcomes, necessitating antihypertensive treatment. However, current data concerning the safety of in utero exposure to antihypertensive medication are controversial. While some studies recommend the administration of certain agents, others underline the possible adverse effects on fetal development. This review aims to summarize the outcomes of studies published during the last decade, referring to first trimester in utero exposure to antihypertensive agents. In general, a-methyldopa, ß-blockers and calcium channel blockers are the first or second treatment line for hypertension during pregnancy. However, ACEIs, ARBs and diuretics are mostly contraindicated, as the potential risk outweighs the benefits of their administration. Additionally, several drugs should be avoided, due to the lack of data regarding their safety. CONCLUSION: As current studies are restricted for ethical reasons, there is a significant lack of evidence concerning diverse antihypertensive agent use. In utero exposure to antihypertensive medication needs to be carefully evaluated and supported by further research.

Cell adhesion molecules' altered profile in benign and malignant salivary gland tumors. The paradigm of beta4-integrin, desmoglein-2, ICAM-1 and CD44s.

BACKGROUND: Alterations in intercellular and cell-extracellular matrix connections contribute to tumour development. This study investigates the expression of specific cell adhesion molecules (CAMs) in salivary gland tumors (SGTs). METHODS: Formalin-fixed, paraffin- embedded tissue specimens of different types of 34 benign and 31 malignant SGTs and normal salivary glands were studied using Envision/HRP immunohistochemical technique for Desmoglein-2 (Dsg-2), beta4-integrin, CD44s and ICAM-1. Intensity of staining was evaluated in a semi-quantitative manner. Results were analyzed using Kendall's τ and Spearman's ρ as correlation criteria. RESULTS: Dsg-2 in intercellular space, beta4-integrin in cell-basal membrane, and CD44s in both types of contacts were strongly expressed in normal acinar and ductal cells, whereas ICAM-1 was expressed only at the endothelium and sparse stromal cells and monocytes. Strong correlation was found between Dsg-2 expression in adenomas and controls and between adenocarcinomas and controls. In adenomas, a distinct cytoplasmic presence of Dsg-2 was observed in addition to the usual membranous expression, with decreased expression in comparison with normal tissue. In malignant SGTs, Dsg-2 expression was absent. In most SGTs, beta4-integrin was expressed also with a distinct pattern, involving the cytoplasm and the unpolarised membrane, while CD44 was found only on the membrane. Strong correlation between beta4-integrin expression in adenomas and controls was noted, while CD44 expression was found to be correlated significantly between adenocarcinomas and controls (p < 0.001). Regarding ICAM-1, its expression was found increased in adenomas, with non-specific distribution in malignant SGTs and strong correlation between the histological subtypes and controls (p < 0.001). CONCLUSION: The different expression profile of CAMs in SGTs could possibly suggest a role on their pathogenesis, representing a model of how neoplastic cells can take advantage of normal tissue architecture and cell-extracellular matrix interactions.