The Effects of Four Compounds That Act on the Dopaminergic and Serotonergic Systems on Working Memory in Animal Studies; A Literature Review.

The dopaminergic and serotonergic systems are two of the most important neuronal pathways in the human brain. Almost all psychotropic medications impact at least one neurotransmitter system. As a result, investigating how they affect memory could yield valuable insights into potential therapeutic applications or unanticipated side effects. The aim of this literature review was to collect literature data from animal studies regarding the effects on memory of four drugs known to act on the serotonergic and dopaminergic systems. The studies included in this review were identified in the PubMed database using selection criteria from the PRISMA protocol. We analyzed 29 articles investigating one of four different dopaminergic or serotonergic compounds. Studies conducted on bromocriptine have shown that stimulating D2 receptors may enhance working memory in rodents, whereas inhibiting these receptors could have the opposite effect, reducing working memory performance. The effects of serotonin on working memory are not clearly established as studies on fluoxetine and ketanserin have yielded conflicting results. Further studies with better-designed methodologies are necessary to explore the impact of compounds that affect both the dopaminergic and serotonergic systems on working memory.

SMAD4 and TGFßR2 expression in pancreatic ductal carcinoma.

Pancreatic ductal carcinoma is the most common type of pancreatic cancer, and currently represents the fourth cause of death by cancer, worldwide. Among classical pancreatic markers that ascertain the histopathology, new emerging targets have been proposed for both diagnostic and prognostic purposes. In the present study, utilizing a group of 28 confirmed resected pancreatic ductal carcinomas, we have assessed the immunoexpression and correlation ratios of mothers against decapentaplegic homolog 4 (Drosophila) (SMAD4)∕transforming growth factor beta receptor 2 (TGFßR2), and vimentin∕cluster of differentiation 105 (CD105). SMAD4 showed an overall increase in tumors versus pancreatic control tissue, but a decrease from G1 towards poorly differentiated tumors, while TGFßR2, vimentin and CD105 showed higher expression values in the tumor areas. Vimentin-CD105 colocalization degree decreased in tumor tissues compared to controls, illustrating a desynchronization of these two markers, both of them being negative in the tumor epithelia. Altogether, it is highly plausible that all these key players revolve around the epithelial-to-mesenchymal transition phenomenon, and this itself modulates the clinical outcome of the patient.

Immunoexpression of p53 and COX-2 in basal cell carcinoma.

Basal cell carcinoma (BCC) is a variety of cutaneous carcinoma associated with an excellent prognosis because it rarely metastasizes, but it can cause significant local destruction and morbidity if surgical excision is not made. In this study, we examined the immunohistochemical expression of p53 and cyclooxygenase-2 (COX-2) in 51 BCCs, nodular and infiltrative subtypes, with various Clark levels. The immunoexpression of p53 was identified in 74.5% BCC cases and COX-2 reactions in 88.2% of cases. The scores of p53 reactions revealed significant differences depending on Clark level and borderline significance with tumor type, the high positive scores being associated to infiltrative tumors and high Clark level. No differences were revealed between COX-2 scores with both Clark level and tumor type. The analysis of the percentage values of p53 and COX-2 indicated a positive linear correlation. The positivity of p53 and COX-2 in a large proportion of BCCs, regardless of histological type and of depth of invasion, supports the two markers involvement in tumor progression.

Prognostic factors in squamous cell carcinoma of the lower lip - an immunohistochemical study.

Squamous cell carcinoma (SCC) of the lip represents 15-30% of SCC of cephalic extremity, located on the lower lip in about 90% of cases. The present paper aimed to define the profile of SCC of the lip with major risk factors. The study included 20 selected cases diagnosed with lower lip SCC, using a panel of antibodies which addressed cell proliferation (Ki67), perturbation of the cell cycle (p53), angiogenesis (VEGF - vascular endothelial growth factor), factors related to tumor cell interaction with the extracellular matrix (CD44). Ki67 immunoexpression was identified in all the cases. Poorly differentiated (PD) SCC presented a mean value of Ki67 positivity index (PI) significantly higher compared to well-differentiated (WD) and moderately differentiated (MD) SCC. We found significantly higher mean values of Ki67 PI in pT3 lesion, compared with pT2 and pT lesions, and with no statistically significant differences in lip SCC with associated lymph node metastasis (pN1), compared to those with no lymph node metastasis (pN0). PD SCC presented a higher mean value of p53 PI compared to WD and MD SCC, but without significant differences. Analysis indicated significantly higher values in pT3 lesions and in pT2 and pT1 and in pN1 SCC. In WD SCC, CD44 immunoexpression had a higher intensity. For PD and MD SCC the immunolabelings presented low÷moderate heterogeneous intensity. WD lip SCC presented a statistically significant higher mean value for CD44 PI compared to MD and PD SCC, and not statistically significant higher in pT1, pT2 then in pT3 and in pN0 cases then in pN1. WD lip SCC presented statistically significant higher mean value of VEGF PI related to those with MD and PD SCC. VEGF PI values were higher in pT1, pT2 then in pT3 and in the pN0 SCC, but without statistically significant differences. We found a positive linear correlation for Ki67÷p53, although statistically not significant and for CD44÷VEGF statistically significant (p=0.001). Also, the analysis identified negative a linear statistically significant correlation for Ki67÷CD44 and for Ki67÷VEGF statistically significant as well (p=0.001). Immunohistochemical investigations in lip SCC, regarding the expression of p53, Ki67, CD44 and VEGF, revealed results that suggest their ability to assess the prognosis and progression of tumor evolution.

Cutaneous mastocytosis, problems of clinical diagnosis of four cases.

Mastocytosis is a rare disease characterized by a pathological increased of mast cells in one or more tissues, particularly in the skin, bone marrow, liver, spleen, lymph nodes and gastrointestinal tract. Cutaneous mastocytosis represents over 90% of cases found with predilection in children. The aim of the paper was to summarize the authors' clinical, histopathological and immunohistochemical observations on patients with cutaneous mastocytosis. We present four cases of cutaneous mastocytosis, sporadic form, customized by clinical presentation and age of onset: two installed in the neonatal period, a case with onset in infancy and another in adulthood. For the assessment of the severity and the effectiveness of the treatment, we used SCORMA Index. We performed in each patient histopathological examination of the skin (Hematoxylin-Eosin and Giemsa stains), the dosage of mediators (serum tryptase level, serum histamine levels, urinary histamine metabolites) and the balance of expansion (complete blood cell count, liver biological investigations, abdominal ultrasound, skeletal radiography, chest radiography). For the adult with mastocytosis, we performed abdominal scanner and cytological study of the bone marrow. Following investigations carried out in each case, we mentioned the diagnosis of cutaneous mastocytosis, and also excluded several diseases confounded by clinically and histologically aspect. Considering the fact that the balance expansion was negative, we excluded the diagnosis of systemic mastocytosis. The presence of anemia and protein energetic malnutrition in children with mastocytosis involves carrying out balance extension for the exclusion of a systemic form of the disease. Histopathological examination of the skin using special stains, the dosage of mediators (serum tryptase level, serum histamine levels, urinary histamine metabolites) and balance expansion establish the diagnosis of cutaneous mastocytosis and also exclude many confusions because of the clinical presentation.

Impact of a new levonorgestrel intrauterine system, Levosert(®), on heavy menstrual bleeding: results of a one-year randomised controlled trial.

OBJECTIVE: To evaluate a new levonorgestrel-releasing intrauterine system (LNG-IUS) called Levosert(®) for the treatment of heavy menstrual bleeding (HMB) in comparison to the reference product Mirena(®). METHODS: A multicentre, randomised, controlled trial, in non-menopausal women diagnosed with functional HMB (defined as menstrual blood loss [MBL] ≥ 80 mL) randomised to either Levosert(®) or Mirena(®) and followed for up to one year. MBL was evaluated using a validated modified version of the Wyatt pictogram. RESULTS: A total of 280 women were randomised (141 to Levosert(®) and 139 to Mirena(®)). During the one-year treatment period, both Levosert(®) and Mirena(®) dramatically decreased MBL and increased haemoglobin and ferritin levels. There were no statistically significant differences between Levosert(®) and Mirena(®) regarding any of the parameters evaluated during the study. Similar bleeding patterns were observed in both groups. Levosert(®) was inserted with the same ease as Mirena(®). Both treatments were associated with identical expulsion rates and no perforations occurred in either treatment group. CONCLUSION: Levosert(®), a new LNG-IUS designed to release the same daily amount of LNG as Mirena(®), is highly effective in the treatment of HMB. No differences were observed between Levosert(®) and Mirena(®) regarding all evaluated outcomes, including safety profile.

Controlled ovarian hyperstimulation and IVF pregnancy prognosis.

IVF (in vitro fertilization) often represents the ultimate step in our attempt to treat infertility. Nowadays this method is more and more used, couple's expectations are higher and higher, so that optimizing the chance that one IVF pregnancy became a healthy newborn child is becoming an important issue. In this study we analyzed the controlled ovarian hyperstimulation impact on IVF pregnancy prognosis. We studied 307 patients who had IVF fresh procedures in "Panait Sirbu" Clinical Hospital of Obstetrics and Gynecology - Department of Assisted Human Reproduction between 01.01.2008 - 31.12.2010 and obtained pregnancy; pregnancy rate according to our statistics is 34%. For statistic analysis we used the odd Student test. Our data proved better results (defined as a better birth/abortion ratio) for the patients where recombinant FSH was used towards patients where highly purified urinary gonadotropin or the combination of the two drugs was used. Our statistical data also proved that none of the variables: age, BMI (body mass index), endometrium thickness, number of oocytes, number of embryos or number of days of stimulation is a favorable variable for this better result, but the number of units of gonadotropin is a favorable variable for a better birth/abortion ratio. We consider that our data gives an interesting perspective upon the connection between controlled ovarian hyperstimulation and pregnancy outcome, especially these days when tendencies are to obtain as many oocytes in one procedure as we can, which often means to use high doses of gonadotropin.

Clinical and morphological correlations in acute ischemic stroke.

We studied the clinical and histopathological changes in twenty-seven cases of acute ischemic stroke, aged between 65 and 75 years. All deaths occurred within 30 days after stroke. The aim of our study was to establish the clinical and histological correlations in acute ischemic stroke to detect prognostic factors. Brain lesions after acute stroke were observed in all regions. Our study describes the heterogeneity of brain injury after acute ischemic stroke with the participation of all brain components and the chronology in which these lesions develop and evolve. By histological and immunohistochemical studies, we identified neuronal, glial and vascular damage. The neurons had undergone in the area of lesion a process of necrosis, ballooning or condensation process. In the ischemic penumbra, we observed the presence of red neurons. Vascular lesions were represented by the discontinuity of capillaries, always associated with a marked perivascular edema. The following clinical and morphological correlations were established: liquefactive necrosis, astrocyte gliosis, phagocytosis phenomena are the more intense the later the death of the patient; apoptosis phenomena are the more intense the faster the death of the patient; the entire cerebral microcirculation presented microscopic modifications following the ischemic strokes, regardless of the time since the lesion occurred and the histological examination was made; the major neurological complications of the ischemic stroke - the hemorrhagic transformation phenomena, cerebral edema, were microscopically objectified, regardless of the time since the lesion occurred and the histological examination was made.

Histological and immunohistochemical aspects of cerebral vessels of the elderly.

The central nervous system is considered the most complex morphological structure of the human body. Between nervous tissue and cerebral circulation is a very close relationship, so transient vascular meningocerebral disturbances cause changes in neuronal function clinically expressed as various neurological signs and symptoms, especially in the elderly. In this study, we examined from the histological and immunohistochemical point of view encephalon fragments collected from 24 patients aged between 46 and 85 years. All patients exhibited changes in meningocerebral vessels, ranging from atheromatous plaques to vascular rupture. Immunohistochemical techniques have shown changes in the vascular endothelium, smooth muscle fibers of arterial walls and blood-brain barrier disruption.

The vasculogenesis--a possible histological identification criterion for the molar pregnancy.

The benign hydatidiform mole (partial and complete) practically represents an associated pathology of the first trimester miscarriage; it is considered that it represents the initial pathology, which, evolutionally, may be followed by the appearance of invasive mole and choriocarcinoma. The authors have studied clinical and cytogenetical 61 cases selected according to some specific criteria for the suspicion of molar pregnancy or hydropic abortion and 21 cases that represented the control group made by patients with normal pregnancy which have been presented for legal abortion. In all cases has been made a histological exam and has been studied the vasculogenesis by immunohistochemistry labeling for CD31 and CD34. Following-up the results has been established a number of histological and immunohistochemical criteria for the evaluation and differentiation of various molar pregnancy types and the vasculogenesis characteristics. The most important differential diagnosis criteria between partial and complete mole is represented by the trophoblast disposition and the atypical trophoblast in the complete mole.