Prevention is better than cure: identifying and dealing with the key features involved in the prevention of gestational diabetes - A bird's eye view.

Gestational diabetes (GDM) is considered to be the most common metabolic problem of pregnancy, which, if not recognized and treated on time, can lead to devastating effects on both the mother's health and the health of the fetus and the newborns. Many studies have revealed that the children born of GDM mothers or grandmothers have higher chances of developing diabetes type I or type II later in their life. Early identification of risk factors can help prevent the appearance of severe GDM and its complications witnessed both in the child and the mother. Obesity is one of the major risk factors that should not be ignored, and obese females should first undergo weight reduction plans in case of planned pregnancies. Other risk factors include a family history of DM arterial hypertension, significant weight gain during pregnancy, short sleep duration, women's exposure to stressful environments, changes in alpha and beta microbiota, and air pollution. Proper care should be provided to females of reproductive age both before and during pregnancy to avoid complications. Awareness programs for healthy lifestyles and diets, oral hygiene maintenance guides, and regular health check-ups can all be considered as a key to a healthy society. Expanding the analysis of gut microbiota in individuals at a heightened risk of GDM can hold particular value, especially during the preconception phase. The alterations in gut microbiota can serve as crucial factors in enhancing lifestyle modifications prior to conception. Further studies are required in this direction to decrease the prevalence of GDM, and efficient measures should be implemented before the consequences appear.

PLASMATIC LEVELS OF NEUROPEPTIDES, INCLUDING OXYTOCIN, IN CHILDREN WITH AUTISM SPECTRUM DISORDER, CORRELATE WITH THE DISORDER SEVERITY.

CONTEXT: Oxytocin has been investigated as a potential medication for psychiatric disorders. OBJECTIVE AND DESIGN: This study prospectively investigates correlations between oxytocin and other neuropeptides plasma levels in patients with autism spectrum disorders (ASD) according to severity and treatment, as compared to controls. SUBJECTS AND METHODS: Thirty-one children (6 neurotypical as control) participated in this study. The patients were classified into mildly and severely-affected, according to Autism Diagnostic Observation Schedule (ADOS) scores. Oxytocin, orexin A and B, α-MSH, ß-endorphins, neurotensin and substance P were investigated using a quantitative multiplex assay or a competitive-ELISA method. RESULTS: Plasma oxytocin levels differed between the groups (F (2, 24) =6.48, p=0.006, η2=0.35, observed power=86%): patients with the mild ASD had higher values of plasma oxytocin than those with the severe form (average difference=74.56±20.74pg/mL, p=0.004). CONCLUSIONS: These results show a negative correlation between plasma levels of oxytocin and the severity of ASD and support the involvement of oxytocinergic mechanisms in ASD.

Simulating real-life exposures to uncover possible risks to human health: A proposed consensus for a novel methodological approach.

In real life, consumers are exposed to complex mixtures of chemicals via food, water and commercial products consumption. Since risk assessment usually focuses on individual compounds, the current regulatory approach doesn't assess the overall risk of chemicals present in a mixture. This study will evaluate the cumulative toxicity of mixtures of different classes of pesticides and mixtures of different classes of pesticides together with food additives (FAs) and common consumer product chemicals using realistic doses after long-term exposure. Groups of Sprague Dawley (CD-SD) rats (20 males and 20 females) will be treated with mixtures of pesticides or mixtures of pesticides together with FAs and common consumer product chemicals in 0.0, 0.25 × acceptable daily intake (ADI)/tolerable daily intake (TDI), ADI/TDI and 5 × ADI/TDI doses for 104 weeks. All animals will be examined every day for signs of morbidity and mortality. Clinical chemistry hematological parameters, serum hormone levels, biomarkers of oxidative stress, cardiotoxicity, genotoxicity, urinalysis and echocardiographic tests will be assessed periodically at 6 month intervals. At 3-month intervals, ophthalmological examination, test for sensory reactivity to different types of stimuli, together with assessment of learning abilities and memory performance of the adult and ageing animals will be conducted. After 24 months, animals will be necropsied, and internal organs will be histopathologically examined. If the hypothesis of an increased risk or a new hazard not currently identified from cumulative exposure to multiple chemicals was observed, this will provide further information to public authorities and research communities supporting the need of replacing current single-compound risk assessment by a more robust cumulative risk assessment paradigm.

PRELIMINARY INSIGHTS IN OXYTOCIN ASSOCIATION WITH THE ONSET OF DIABETIC NEUROPATHY.

Diabetes is one of the most prevalent chronic disorders, associating numerous somatic and behavioral modifications. Oxytocin has been widely studied for its involvement in social behavior and psychiatric disorders. This pilot study presents a series of 3 patients with type 1 diabetes and diabetic neuropathy in which the values of plasma oxytocin, neurotensin, ß-endorphins, α-MSH, substance P and orexin A were measured in comparison to 3 healthy controls with matching ages. In the diabetic patients group, there was a strong negative correlation between the value of plasma glucose and oxytocin (r=-0.99, p=0.04), respectively neurotensin (r=-0.99, p=0.03). These values did not correlate in the control group. The results suggest that oxytocin, in conjunction with neurotensin, could be investigated as a potential early detection marker of diabetic neuropathy and, to our knowledge, this is the first report focusing on plasma oxytocin levels in patients with diabetic neuropathy.

Preeclampsia screening from the patient's perspective.

Preeclampsia represents an important cause of maternal and fetal morbidity and mortality. The early identification of pregnant women at risk represents a priority in reducing preeclampsia complications. For a better evaluation of the importance of preeclampsia screening, a questionnaire was developed. Methods. The questionnaire based on 14 items was distributed online. The form was anonymously completed. All forms consisted of simple questions. Results. Data from 151 completed forms were collected and analyzed. The analysis revealed the importance of arterial pressure control. 15% of the responders needed hypertensive treatment in pregnancy. They were interested in completing the preeclampsia risk test (88%). Conclusions. The results suggested that preeclampsia screening and measurement of the atrial pressure may become a valuable tool for evaluating and for determining the diagnosis in question, but the possibility of emotional distress for the subjects at risk of developing the condition should be taken in consideration.

THE ROLE OF ESTROGENS AND ESTROGEN RECEPTORS IN MELANOMA DEVELOPMENT AND PROGRESSION.

Melanoma has a significant mortality and its growing incidence is associated with important social and health care costs. Thus, investigation of the complex mechanisms contributing to emergence and development of melanoma are of real interest both in scientific research and clinical practice. Estrogens play an important role in the emergence and development of certain types of cancer, such as breast cancer, endometrial cancer and ovarian cancer, but their role in development of cutaneous melanoma is still a matter of debate. Various data suggest that increased levels of endogenous estrogens during pregnancy or exposure to exogenous estrogens by use of oral contraceptives (OCs) and hormone replacement therapy (HRT) may have a potential role in melanoma development and progression. Moreover, there were revealed several intracellular pathways which can support the connection between estrogens, estrogen receptors (ER) and melanoma. While ER-ß plays an antiproliferative role, ER-α promotes cell growth and cellular atypia. Thus, inhibition of ER-ß activity in the skin can increase the risk for development of cutaneous melanoma and spread of metastatic cells. However, despite recent advances in this area, the exact role and clinical implications of estrogens and estrogen receptors in melanoma are still not entirely understood and require further investigations.

From punishment to education--juvenile delinquency in Romanian criminal law.

For centuries children were considered "mini-adults". Together with expressing the need to educate children and putting a stop to their integration in the work field from the earliest years the 19th century also displayed a new image of the child, which clearly separates him from the adults. In this paper the authors analyze the Romanian legislation addressing juvenile delinquency in criminal temporal evolution. On the one hand the minority age limits are sought and modulation of legislative provisions according to these, and on the other hand, types of penalties for minors are discussed. The authors conclude that the approach to juvenile delinquency in the current Romanian Criminal Code is the result of a long process of reflection of the legislators on adopting a different system of sanctions for juvenile offenders and on creating special regulations concerning the prosecution, trial and enforcement of the decisions regarding them.

Utility of autopsy in medical education--students' opinions and attitudes.

UNLABELLED: Autopsy has been for centuries part of medical education, providing benefits to medical students in terms of knowledge, skills, and development of respect, empathy and compassion. AIM: To evaluate the utility of autopsy in medical education based on the opinions and attitudes of medical students. MATERIAL AND METHODS: A questionnaire was applied to 219 medical students. The answers were grouped according to two main themes: the utility of autopsy in medical education and students' attitudes toward autopsy. RESULTS: Most of the respondents considered that autopsy is useful to society, medical practice and medical education. On average, participants felt "moderately uncomfortable" on exposure to the first autopsy. CONCLUSIONS: Our study indicates the need for medical education to emphasize the utility of autopsy in the medical practice. Extracurricular activities to deepen the medico-legal knowledge and skills would be beneficial for the students who are particularly interested in this specialty. It is also necessary to take into account the possible negative psychological reactions of the students caused by the first exposure to autopsy and identify adequate methods to solve them.

Anti-Mullerian hormone--a prognostic marker for metformin therapy efficiency in the treatment of women with infertility and polycystic ovary syndrome.

BACKGROUND: The anti-Mullerian hormone (AMH) is secreted in women exclusively by the granulosa cells of the ovarian follicles. The serum level of AMH is a precise marker of follicle pool size. In recent clinical studies of polycystic ovary syndrome (PCOS), the serum levels of AMH were elevated about two to threefold. The use of metformin in women with infertility and PCOS has proved to be efficient: restoring ovulation and reducing metabolic dysfunctions. The aim of our study is to assess AMH as a prognostic marker for metformin therapy efficiency in the treatment of women with infertility and polycystic ovary syndrome (PCOS). METHODS: Eleven patients with infertility and PCOS were enrolled; PCOS was diagnosed according to the criteria of Androgen Excess and Polycystic Ovarian Syndrome Society 2006 (AE/PCOS). All patients have received metformin therapy. Serum AMH was recorded before and after 2 months of treatment; the normal laboratory values were 2.0-6.8 ng/ml. RESULTS: The primary serum AMH level of all women in study was very high: 8.99±0.99 ng/ml. After 2 months of treatment with metformin ovulation was restored in all the patients and the serum AMH levels were significantly decreased. CONCLUSIONS: In clinical practice, serum AMH levels of women with infertility and PCOS receiving metformin are a useful predictive marker for the treatment efficiency.

The role of confocal microscopy in the dermato-oncology practice.

Reflectance-mode confocal microscopy (RCM) is a new in vivo skin imaging technique. We present our one-year experience in RCM examinations in skin tumors and the retrospective analysis of patients enrolled in the Dermatological Department of 'N. Paulescu' Institute using the Fotofinder Dermoscope IIW for the dermatoscopy analysis and VivaScope 1500W for in vivo RCM. We established the rank of RCM in the complex algorithm of skin cancer diagnose, showing that the presented experience can open new possibilities to implement this automated image analyzing system in the routine practice. Our analyzed cases clearly showed that confocal microscopy, therefore, optical biopsy, could guide the clinician towards an accurate diagnosis before surgical removal. Moreover, we emphasized that the development of this technique increases the potential of future teledermatologic applications.

The kinetics of cell adhesion to solid scaffolds: an experimental and theoretical approach.

The process of cell seeding on biocompatible scaffolds has a major impact on the morphological evolution of an engineered tissue because it involves all the key factors of tissue formation: cells, matrix, and their mutual interactions. In order to characterize the efficiency of cell seeding techniques, mainly static parameters are used such as cell density, cell distribution, and cell viability. Here, we present an experimental model that incorporates an optical density meter providing real-time information on the cell seeding velocity, a relevant dynamic parameter of cell-matrix interaction. Our setup may be adapted to fit various cell seeding protocols. A modified fluorimetric cuvette is used as bioreactor culture flask. The optical density of the magnetically stirred cell suspension is recorded by a digital optoelectronic device. We performed calibration experiments in order to prove that, in our experimental conditions, optical density depends linearly on the number of cells in the unit volume of suspension. Control studies showed that, during the time course of a typical experiment (up to 10 h), the cells (murine 3T3 fibroblasts) neither aggregated nor adhered significantly to the walls of the cuvette. Hence, our setup yields the number of cells attached to the scaffold as a function of time. In order to analyze the experimental seeding curves, we built a kinetic model based on Langmuir's adsorption theory, which was extended to include a preliminary step of integrin function recovery. We illustrate the proposed approach by two sets of experiments that involved trypsin-EDTA or only EDTA treatment (no trypsin) used to detach the cells from the culture flasks. The data indicate that in both cases cell-matrix adhesion has a sequential, two-step dynamics, but kinetic parameters and attachment site availability depend on the experimental protocol.

The in vitro effect of a low molecular weight heparin, nadroparin (Fraxiparine), on leukocytes obtained from patients with vascular diseases.

BACKGROUND: Both lymphocytes and granulocytes may play a role in the immune system-mediated inflammatory response associated with non-Q wave infarction and aortic aneurysms. METHODS: The purpose of this study was to establish the in vitro effects of a low molecular weight heparin (LMWH), nadroparin (Fraxiparine), on some functional parameters of peripheral granulocytes and lymphocytes isolated from control subjects and patients with aortic aneurysm or non-Q wave infarction. RESULTS: Nadroparin (0.06-600 AXaU/ml) exerted different in vitro effects on granulocytes and lymphocytes isolated from normal subjects and the patient groups. The following indices were assessed: superoxide anion release, lymphocyte proliferation, phagocytic activity and the cellular respiratory burst. The effects of nadroparin varied according to the patient group and the index of lymphocyte/granulocyte assessed. CONCLUSIONS: Since peripheral granulocytes isolated from these patients are activated, the observed inhibition exerted by nadroparin on superoxide anion release may be beneficial. LMWHs have additional effects that are independent of their anticoagulant activity. These effects may influence the "inflammatory component" of the atherosclerotic process.

On the Na+,K+ pump in fluctuating membrane potentials.

The present work investigates the usefulness of noise in the activity of the Na+,K+ pump. Random gating activity of the neighboring ion channels causes local fluctuations of the electric potential. They are modeled by a Markovian symmetric dichotomic noise, added to the membrane potential. The noise-averaged pump current is calculated for a general rectangular voltage signal and the model parameters of the effective two-state enzyme cycle are tuned to fit experimental results. Then, using these parameters, the amount of transported charge is calculated, and studied as a function of noise intensity. Signal and noise characteristics are identified at which fluctuations enhance pump activity. The biological impact of this phenomenon seems to be absent in physiological conditions for it occurs at noise amplitudes over 50 mV, which are unlikely to appear due to ion channels. However, under some conditions, externally applied dichotomic noise of intensity about 150 mV may sensibly increase the quantity of transported charge.

Fluctuations and the Hofmeister effect.

The Hofmeister effect consists in changes of protein solubility triggered by neutral electrolyte cosolutes. Based on the assumption that salts cause stochastic fluctuations of the free energy barrier profiles, a kinetic theory of this phenomenon is proposed. An exponentially correlated noise, of amplitude proportional to the salt concentration, is added to each energy level, and the time-dependence of the mean protein concentration is calculated. It is found that the theory yields the well-known Setschenow equation if the noise correlation time is low in comparison to the aggregation time constant. Experimental data on salting-in agents are well fitted, whereas, in the case of salting-out cosolutes, two independent dichotomic fluctuations are needed to fit the data. This may result from the fact that, in both cases, the low-concentration regime is dominated by salting-in electrostatic contributions, whereas, at high salt concentrations, electron donor/acceptor interactions become important; these have opposite effects. The theory offers a novel way to metricate Hofmeister effects and also leads to thermodynamic quantities, which account for the influence of salts. The formalism may also be applied to describe kinetic phenomena in the presence of cosolutes.

Protection against simian immunodeficiency virus vaginal challenge by using Sabin poliovirus vectors.

Here we provide the first report of protection against a vaginal challenge with a highly virulent simian immunodeficiency virus (SIV) by using a vaccine vector. New poliovirus vectors based on Sabin 1 and 2 vaccine strain viruses were constructed, and these vectors were used to generate a series of new viruses containing SIV gag, pol, env, nef, and tat in overlapping fragments. Two cocktails of 20 transgenic polioviruses (SabRV1-SIV and SabRV2-SIV) were inoculated into seven cynomolgus macaques. All monkeys produced substantial anti-SIV serum and mucosal antibody responses. SIV-specific cytotoxic T-lymphocyte responses were detected in three of seven monkeys after vaccination. All 7 vaccinated macaques, as well as 12 control macaques, were challenged vaginally with pathogenic SIVmac251. Strikingly, four of the seven vaccinated animals exhibited substantial protection against the vaginal SIV challenge. All 12 control monkeys became SIV positive. In two of the seven SabRV-SIV-vaccinated monkeys we found no virological evidence of infection following challenge, indicating that these two monkeys were completely protected. Two additional SabRV-SIV-vaccinated monkeys exhibited a pronounced reduction in postacute viremia to <10(3) copies/ml, suggesting that the vaccine elicited an effective cellular immune response. Three of six control animals developed clinical AIDS by 48 weeks postchallenge. In contrast, all seven vaccinated monkeys remained healthy as judged by all clinical parameters. These results demonstrate the efficacy of SabRV as a potential human vaccine vector, and they show that the use of a vaccine vector cocktail expressing an array of defined antigenic sequences can be an effective vaccination strategy in an outbred population.

Effects of synovial fluid on the respiratory burst of granulocytes in rheumatoid arthritis.

Neutrophil infiltration in the synovia is an important feature of the local inflammatory process associated with rheumatoid arthritis. The present study is focused on the effects exerted in vitro by the synovial fluid versus serum on the respiratory burst of granulocytes isolated either from blood or synovial fluid of rheumatoid arthritis patients. The respiratory burst was evaluated as superoxide anion release, by lucigenin-amplified chemiluminescence. Our data show that the respiratory burst of granulocytes isolated from rheumatoid arthritis patients might trigger a significant oxidative stress both in periphery and the inflamed joint. These cells show no pathological pattern when activated in vitro by the chemotactic peptide fMLP, heterologous synovial fluid or serum. Acellular synovial fluid amplifies the superoxide anion release induced by fMLP more than the corresponding serum, indicating that a bacterial infection in the joint might enhance the oxidative damage in the inflamed synovium.

Flow cytometry measurements of intracellular Ca2+ in K 562 cells.

The aim of this study is to show the intracellular Ca2+ changes induced by methotrexate, a cell cycle inhibitor, in order to prove the intracellular Ca2+ implication in cell proliferation processes. The fluorescent dye used to measure this parameter is Fluo-3, a fluorescein derivative useful for measuring the kinetics of Ca2+ transitions, waves and oscillations. The alterations of Ca2+ concentration proper to K562 cells have been studied, using methotrexate as a cell activation factor, both as direct effects on the cell response (1-15 minutes), and effects in time (24h.), using methotrexate in the culture medium. The K562 response at Ca2+ level in time remained constant for the cells grown in methotrexate medium, showing a slight increase in the control medium. We proved that methotrexate, a cell cycle inhibitor decreased the cytoplasmatic Ca2+ concentration in K562 cells, soon after adding methotrexate both to T0 and T1.

Peripheral leukocytes activation in aortic aneurysmal disease.

The pathogenesis of aneurysmal disease involves factors acting over time. A sustained chronic inflammatory reaction is observed in association with initiations, maintenance, rapid growth and rupture of aortic aneurysms. This study was designed to identify the possible pathogenic role of the inflammatory cells in the outcome of aneurysmal disease, testing the activation state of peripheral lymphocytes and neutrophils. Circulating activated lymphocytes and repeated peaks of neutrophils activation in sequential follow-up is associated with larger aneurysms, mural thrombosis, tendency to aneurysm extension and rupture.

[Parinaud's dermoepithelioma]. / Consideratiuni asupra dermoepiteliomului Parinaud.

The paper presents the clinical and histopathological findings in 18 cases with Parinaud dermoepithelioma an uncommon tumor of the conjunctiva, in a retrospective study made on patients who were investigated in our clinic, during January 1975-January 1995.

The immune response induced by a split influenza vaccine. Studies on cellular immunity.

The aim of this study is to evaluate the effects exerted in vivo upon the general reactivity of the immune system by a commercial split influenza vaccine produced by the Cantacuzino Institute, Bucharest-Romania. The vaccine was intramuscularly administered to 14 volunteers with no precedent of influenza vaccination and no major immune disorders. We have investigated in vitro the polyclonal proliferation of peripheral lymphocytes and the phagocytosis developed by peripheral granulocytes, before and three weeks after vaccination. Our experimental results indicate that the vaccine might have a modulatory action on peripheral leukocyte concentration induces the activation of polyclonal lymphocyte proliferation and of the phagocytosis potential of granulocytes. These effects are not dependent on the age of the vaccinees.