Factors that Impact Caregivers of Patients with Schizophrenia.

Schizophrenia, a term first introduced by Eugen Bleurer in 1911, is a controversial topic, a symbol of profound behavioral and personality disorders. Although schizophrenia mainly affects the patients, directly, it indirectly affects their caregivers. Because caregivers of subjects with schizophrenia experience significant burden in taking care of the patient, usually over a long period of time, we decided to analyze some of the factors that can impact the perceived level of stress. Our study group consisted of caregivers 124 patients with schizophrenia, interviewed between January 2018 and July 2019. We analyzed demographic, clinical and other medical variables of patients and caregivers. We also evaluated caregivers' burden, using the adapted Zarit interview. The average Zarit score in our study was 42.36±8.64, which shows moderate to high burden. Several factors that influence the perceived burden of the caregiver have been identified, such as patient gender, age of onset, patient and caregiver marital status, patient level of education and social functioning, caregiver age, somatic comorbidities and therapeutic compliance of the patient.

Functional antagonism of ß-arrestin isoforms balance IGF-1R expression and signalling with distinct cancer-related biological outcomes.

With very similar 3D structures, the widely expressed ß-arrestin isoforms 1 and 2 play at times identical, distinct or even opposing roles in regulating various aspects of G protein-coupled receptors (GPCR) expression and signalling. Recent evidence recognizes the ß-arrestin system as a key regulator of not only GPCRs, but also receptor tyrosine kinases, including the highly cancer relevant insulin-like growth factor type 1 receptor (IGF-1R). Binding of ß-arrestin1 to IGF-1R leads to ligand-dependent degradation of the receptor and generates additional MAPK/ERK signalling, protecting cancer cells against anti-IGF-1R therapy. Because the interplay between ß-arrestin isoforms governs the biological effects for most GPCRs, as yet unexplored for the IGF-1R, we sought to investigate specifically the regulatory roles of the ß-arrestin2 isoform on expression and function of the IGF-1R. Results from controlled expression of either ß-arrestin isoform demonstrate that ß-arrestin2 acts in an opposite manner to ß-arrestin1 by promoting degradation of an unstimulated IGF-1R, but protecting the receptor against agonist-induced degradation. Although both isoforms co-immunoprecipitate with IGF-1R, the ligand-occupied receptor has greater affinity for ß-arrestin1; this association lasts longer, sustains MAPK/ERK signalling and mitigates p53 activation. Conversely, ß-arrestin2 has greater affinity for the ligand-unoccupied receptor; this interaction is transient, triggers receptor ubiquitination and degradation without signalling activation, and leads to a lack of responsiveness to IGF-1, cell cycle arrest and decreased viability of cancer cells. This study reveals contrasting abilities of IGF-1R to interact with each ß-arrestin isoform, depending on the presence of the ligand and demonstrates the antagonism between the two ß-arrestin isoforms in controlling IGF-1R expression and function, which could be developed into a practical anti-IGF-1R strategy for cancer therapy.

Which is the Best Imaging Method in Pancreatic Adenocarcinoma Diagnosis and Staging - CT, MRI or EUS?

INTRODUCTION: Imaging has a decisive role in the diagnosis and staging of pancreatic cancer, the most used imaging methods being computed tomography, magnetic resonance imaging and endoscopic ultrasonography. MATERIAL AND METHOD: They were studied retrospectively over a 3 years period, 140 patients with pancreatic cancer. AIM OF THE STUDY: This study aims to determine the effectiveness of CT, MRI and EUS in diagnosis and staging of panceatic cancer. RESULTS: CT showed a diagnostic accuracy of 83.3%, with sensitivity and specificity of 81.4% and 43% respectively. MRI showed superior diagnostic accuracy compared to CT (89,1%). However, EUS demonstrated the best diagnostic value in PC (accuracy of 92,7%). Concerning the locoregional staging, the 3 diagnostic methods showed similar result. There were no significant differences concerning the diagnosis of intra-abdominal metastases. Differences have appeared in the case of extra-abdominal. Thus, there were 4 cases of lung metastases which have been identified only on CT and MRI. CONCLUSION: EUS is the most effective technique used in the diagnosis of pancreatic cancer, the present study demonstrating an accuracy of 92.7%. Moreover, EUS offers the possibility to collect samples for cytological examination by EUS guided fine needle aspiration. However, there are some limitations of EUS in identifying extra-abdominal metastases. Thus, the assessment of tumor extension must be completing by performing CT or MRI.

Positive and Negative Predictive Factors for Treatment Response in Patients with Chronic Viral C Hepatitis.

More than 200 million people worldwide are infected with hepatitis C virus. In the United States, suggested estimates are that more than 5 million people live with HCV. The purpose of this paper is to identify, within the Southwestern Romanian population, host factors associated with the response to Pegylated Interferon and Ribavirin treatment for Hepatitis C virus infection. We investigated several factors and their correlation to sustained virological response. The study included 267 patients diagnosed with chronic Hepatitis C between 2013 and 2016, treated with Pegylated Interferon and Ribavirin in the 2nd Medical Department of the Emergency County Hospital Craiova. From the 267 patients included in this study, 149 (55,81%) achieved sustained virological response during the 48 weeks of treatment. Several factors were taken in consideration regarding the treatment response. Positive predictive factors for achieving sustained virological response were: the female gender (35,96%), Low Viral Load at the beginning of treatment, Early Virological Response 75 (28,09%), Rapid Virologic Response133 (49,81%), and stage of fibrosis, with Stage F1 having the highest rate of Sustained Virological Response during double therapy 81 (30,34%). Although at the present time a number of more effective antiviral products have been approved for the treatment of viral hepatitis C, in our country the standard of treatment remains with PegInterferon and Ribavirin therapy. Multiple clinical and paraclinical tools can identify patients with a high chance of responding to treatment, or those who, during treatment, do not meet the criteria for prolonging therapy.

Histiocytosis X and Pericarditis - A Rare Association and a Difficult Diagnosis.

Histiocytic disorders are a group of rare diseases with systemic involvement and with multiple clinical manifestations. We present the case of a 51 years old patient investigated for dyspnea with orthopnea, dry cough, asthenia, muscular weakness and ataxia. The association of previous symptoms with skin lesions, diabetes insipidus, partial hypophyseal insufficiency and pericarditis induced many diagnostic debates. The diagnosis is Histiocytosis X must be sustained by tissue biopsy with immunohistochemical assay or genetic testing. The particularity of our patient is the presence of pericarditis, rarely associated with histiocytosis. Collaboration between medical specialties is mandatory in order to treat this disorder.

Liver Fatty Acid Binding Protein And Hemojuvelin - Potential Biomarkers For Liver Function in Rat Model.

PURPOSE: The purpose of the present study was to investigate whether the co-administration of aripiprazole and fluoxetine could produce impaired liver function in Wistar rats by means of liver fatty acid binding protein (L-FABP) and hemojuvelin (HJV) serum levels. Furthermore, the experiment intended to assess the salivary levels of L-FABP and HJV and to determine whether they correlate with the serum levels of the two markers. MATERIALS AND METHODS: Adult male Wistar rats were randomly assigned to four groups: control (saline 10ml/kg), aripiprazole (4.05 mg/kg), fluoxetine (10 mg/kg) and aripiprazole + fluoxetine (4.05 mg/kg + 10 mg/kg). The drugs were administered by gavage, daily at the same hour, along a 6 week period. L-FABP and HJV levels were determined in serum, from intraventricular blood, and in saliva. Also from intraventricular blood, serum levels for aspartate aminotransferase (ASAT) and alanine amino transferase (ALAT) were assessed. RESULTS: Positive and statistically significant correlations between serum and salivary levels of L-FABP and HJV were found. Aripiprazole + fluoxetine group experienced increased serum L-FABP levels than aripiprazole and fluoxetine groups, and salivary L-FABP as compared to aripiprazole group; but it registered decreased levels for serum and salivary HJV, for ASAT and ALAT than aripiprazole and fluoxetine groups, and for salivary L-FABP compared to fluoxetine group. CONCLUSIONS: The data indicate that: aripiprazole coprescribed with fluoxetine do not cause additional alterations in liver function; L-FABP and HJV levels can be helpful as biomarkers for impaired function of hepatocytes; and that their salivary determination can replace serum determination.

The Estrogen-Induced Effects on Myometrium Are the Result of Activation of Two Different Receptor Types: GPER and ERα.

GPER (G protein coupled estrogen receptor 1), a particular estrogen binding site, is ubiquitously present in human tissues, but its precise physiological role is still very disputed. GPER is associated with normal and abnormal estrogen-dependent proliferations in female tissues and is involved in generation of rapid estrogenic answers. A very important fact is that GPER-induced genomic effects are additive to those mediated by "classic" estrogen receptors, but regarding the rapid effects, as we prove in this study, these can be significant different or even antagonistic.

Pegylated Interferon-Induced Sarcoidosis Presenting With Anterior Uveitis in a Patient with Chronic Hepatitis C - Case Report.

Sarcoidosis is a chronic inflammatory systemic disorder of unknown etiology. It is known to be triggered by an autoimmune process, and is currently recognized as a rare adverse event to interferon therapy for Hepatitis C Virus Infection. Clinical presentation of interferon-triggered sarcoidosis is varied, but ocular manifestation as a first symptom was only once, previously reported. We report the case of a 32 year old woman, infected with hepatitis C, for whom antiviral therapy was initiated. Prior to treatment, the patient had outstanding medical history. Three months from the initiation, patient accused pain and redness of the left eye and mild visual loss. The diagnosis of Interferon induced sarcoidosis was established. We are presenting this case because it illustrates the possibility of sudden and severe complications and we want to emphasize the importance of performing ophthalmological examination in patients treated with pegylated interferon α.

Neuronostatin is co-expressed with somatostatin and mobilizes calcium in cultured rat hypothalamic neurons.

Neuronostatin (NST) is a newly identified peptide of 13-amino acids encoded by the somatostatin (SST) gene. Using a rabbit polyclonal antiserum against the human NST, neuronostatin-immunoreactive (irNST) cells comparable in number and intensity to somatostatin immunoreactive (irSST) cells were detected in the hypothalamic periventricular nucleus. Fewer and/or less intensely labeled irNST cells were noted in other regions such as the hippocampus, cortex, amygdala, and cerebellum. Double-labeling hypothalamic sections with NST- and SST-antiserum revealed an extensive overlapping of irNST and irSST cells in the periventricular nucleus. Pre-absorption of the NST-antiserum with NST (1 microg/ml) but not with SST (1 microg/ml) abrogated irNST and vice versa. The activity of NST on dissociated and cultured hypothalamic neurons was assessed by the Ca(2+) imaging method. NST (10, 100, 1000 nM) concentration-dependently elevated intracellular Ca(2+) concentrations [Ca(2+)](i) in a population of hypothalamic neurons with two distinct profiles: (1) a fast and transitory increase in [Ca(2+)](i), and (2) an oscillatory response. Whereas, SST (100 nM) reduced the basal [Ca(2+)](i) in 21 of 61 hypothalamic neurons examined; an increase was not observed in any of the cells. Optical imaging with a slow-responding voltage sensitive dye DiBAC(4)(3) showed that NST (100 nM) depolarized or hyperpolarized; whereas, SST (100 nM) hyperpolarized a population of hypothalamic neurons. The result shows that NST and SST, though derived from the same precursor protein, exert different calcium mobilizing effects on cultured rat hypothalamic neurons, resulting in diverse cellular activities.

Endometrial stromal sarcoma: clinico-pathological report of four cases and review of the literature.

Endometrial stromal sarcoma (ESS) represents a very rare pathological entity occurring as a malignant disease in women genital sphere. Our clinical report is based on a group of four women aged 37, 48, 50 and 70-year-old, that have been histologically diagnosed with endometrial stromal sarcoma. The most common symptom sending the patient to the physician has been the vaginal bleeding, occurring in all patients. Other associated symptoms were the abdominal enlargement and the presence of the pelviabdominal mass generated by the tumor, low to medium abdominal pain or polakiuria. Two patients were diagnosed with ESS after accomplishing a biopsic curettage of the uterus. Total abdominal hysterectomy and salpingo-oophorectomy have been successfully performed for all of the patients. Adjuvant therapy-radiotherapy has been administered to three patients. At this time, none of the patients died of the disease. Our paper also includes a concise review of the literature in order to have an up-to-date conception regarding diagnosis, therapy and outcome for ESS.

Morphopathological changes induced by the Obstetrical Antiphospholipid Antibody Syndrome in fetal adnexa and uterus.

The Obstetrical Antiphospholipid Antibody Syndrome (OAAS) is representing a separate entity of the global Antiphospholipid Antibody Syndrome (APS), focusing the pregnancy morbidity. OAAS is generating morphopathological changes in almost all components of the gestational biologic transitory system (GBTS): placenta, umbilical cord or uterine wall. The most important, serious and lengthened anomalies are occuring in placenta. Our research has been developed on a group of 68 patients diagnosed with OAAS, initially using the Sapporo criteria and later using the "Sydney" ones. There have been morphopathologically examined: placenta, umbilical cord and myometrium. Histological examination revealed on one hand macroscopic modifications: fibrinoid deposits, white or red placental infarctions, intervillous thrombosis, marginal or basal decidual hematoma, calcareous deposits, umbilical cord thrombosis, and on the other hand microscopic findings: placental infarction, fibrinoid necrosis, myometrial thrombosis, degenerative myometrial disorders, focal myometrial necrosis, villous stasis and necrosis, umbilical cord thrombosis. Because of the increased prothrombotic background, in APS, any vessel or organ could be involved, with no exception for GBTS elements. The basis of the pregnancy morbidity from the obstetrical APS is represented by the morphopathological changes occurring in fetal adnexa and uterine structures.

[Experimental study of the use of piritramide as intrathecal analgesic]. / Cercetari experimentale privind utilizarea piritramidei ca analgezic intratecal.

Opioids proved their advantages as general and intrathecal (i.t.) analgesics. Piritramide (P), a largely used analgesic opioid today, has not been studied in i.t. administration. Our experimental research aimed in determining the efficiency, security and optimal dose of i.t. P. In 9 adult mongrel dogs equally randomized in 3 groups we injected i.t. P 1.3 mg x kg-l (group 1), P 0.8 mg x kg-l (group 2) and sodium chloride 0,9% (group 3) and we registered the motility, the pain reaction to electrical and mechanical nociceptive stimuli, the respiratory rate and amplitude, electrocardiogram, heart rate, mean arterial blood pressure electroencephalogram and, for 2 subjects from group 1, electromyogram. The P-induced analgesia was strong, dose-dependent, and segmental, with a time of onset of 5-8 min, duration of 1h 45 min-2h 30 min, and prolonged residual analgesic level for 5-6 h. The dogs from the 1st group presented moderate side effects: bradypnea, tachycardia and arterial hypotension at 5 min, reduction in the posterior limbs motility, sleep. We could conclude that i.t. piritramide 0.8 mg x kg-l provides a solid, segmental, long-lasting analgesia, without marked adverse effects.

Pre-emption dimensional study aiming to obtain significant statistical results for the variation of serum cortisol during ovarian stimulation.

UNLABELLED: Ovarian stimulation has an important place in the contemporary impressive development of infertility treatment. There are few and not concordant data concerning its influence on cortisol serum levels. AIM: The present study aimed at finding the necessary number of determinations in order to statistically assess the variation of cortisol during and caused by the ovarian stimulation. METHODS: In 25 consecutive infertile women (23-45 years old, average: 32.4 years) enrolled in an ovarian stimulation program (gonadotropin releasing hormone agonist--busereline--from the first day of the cycle, human menopausal gonadotropin beginning with the 14th day of the cycle, ovulation triggering by human chorionic gonadotropin), serum cortisol was measured one month before the study, the 1st, 14th, 16th, 19th, 22nd, 24th day, the day before the triggering of the ovulation, one, two, 19 days and one month after triggering. General methods of data analysis map into descriptive and inferential statistics were used, with BMDP, SAS 6.0 and Epilnfo 5 software. RESULTS AND CONCLUSIONS: The calculated number of determinations, in order to obtain a significant statistical variation of cortisol for the studied set of samples and stimulation protocol is between 28-35--but smaller (15 and 19) around ovulation triggering and 39 patients for a > or = 5% variation compared to control values. The suppositions considered in the present paper seem to offer a correct estimation for obtaining the size of the sample sets to be analyzed in a future study.

Contractile effects by intracellular angiotensin II via receptors with a distinct pharmacological profile in rat aorta.

1. We studied the effect of intracellular angiotensin II (Ang II) and related peptides on rat aortic contraction, whether this effect is pharmacologically distinguishable from that induced by extracellular stimulation, and determined the Ca2+ source involved. 2. Compounds were delivered into the cytoplasm of de-endothelized aorta rings using multilamellar liposomes. Contractions were normalized to the maximum obtained with phenylephrine (10(-5) M). 3. Intracellular administration of Ang II (incorporation range: 0.01-300 nmol mg(-1)) resulted in a dose-dependent contraction, insensitive to extracellular administration (10(-6) M) of the AT1 receptor antagonist CV11947, the AT2 receptor antagonist PD 123319, or the non-selective AT receptor antagonist and partial agonist saralasin ([Sar1,Val5,Ala8]-Ang II (P<0.05). 4. Intracellular administration of CV11947 or PD 123319 right shifted the dose-response curve about 1000 fold or 20 fold, respectively. PD 123319 was only effective if less than 30 nmol mg(-1) Ang II was incorporated. 5. Contraction was partially desensitized to a second intracellular Ang II addition after 45 min (P<0.05). 6. Intracellular administration of Ang I and saralasin also induced contraction (P<0.05). Both responses were sensitive to intracellular CV11947 (P<0.05), but insensitive to PD 123319. The response to Ang I was independent of intracellular captopril. 7. Contraction induced by extracellular application of Ang II and of Ang I was abolished by extracellular pre-treatment with saralasin or CV11947 (P<0.05), but not with PD 123319. Extracellular saralasin induced no contraction. 8. Intracellular Ang II induced contraction was not affected by pre-treatment with heparin filled liposomes, but completely abolished in Ca2+-free external medium. 9. These results support the existence of an intracellular binding site for Ang II in rat aorta. Intracellular stimulation induces contraction dependent on Ca2+-influx but not on Ins(1,4,5)P3 mediated release from intracellular Ca2+-stores. Intracellular Ang I and saralasin induce contraction, possibly via the same binding site. Pharmacological properties of this putative intracellular receptor are clearly different from extracellular stimulated AT1 receptors or intracellular angiotensin receptors postulated in other tissue.

[Laboratory studies of the effect of Pavulon on the blood pressure in induced autonomic dystonias]. / Cercetari de laborator referitoare la influenta Pavulon-ului asupra presiunii sanguine, în functie de unele distonii vegetative provocate.

In experimental studies performed in dogs Pavulon enhances the hypertensive effects of para- and orthosympathicomymetics (nicotinelike and liberation of cathecholamine respectively), parasympaticolytics lowering essentially the rise of the blood pressure induced by Pavulon, which sympathicolytics--depending on the dose administered--can decrease until zero. These facts have a significant role in the anesthesia and intensive care practice.

[Influence of changes in the vegetative tonus on the effects of succinylcholine on blood pressure (experimental data)]. / Influenta variatiilor tonusului vegetativ asupra efectelor succinilcolinei care privesc presiunea sanguina (date experimentale)

Intravenous administration of small amounts (0,1 mg/kg of body weight) of succinyl-choline in dogs results in the increase of blood pressure through nicotine-like effects. The increase of succinyl-choline doses induces at first a lowering of the blood pressure through a muscarine-like effect, then its increase. Atropinization, as well as prealable vagotomy, prevents the lowering of the blood pressure but increases it through a nicotine-like effect. Neomistigmine increases both the nicotinic and the cholinergic (muscarinic) effects of succinyl-choline. The use of alpha-sympatico-mimetic drugs, followed by administration of succinyl-choline, generates hypertension and conjugation of alpha-sympatico-mimetic drugs with lepto-currarine induces hypotension, even when para-sympatic lysis has been performed in advance. Inhibition of the beta-sympatic components, followed by inhibition of the alpha-sympatic ones, prevents the development of the succinyl-cholinic hypotension. These facts indicate that the action of succinyl-choline on the blood pressure depends, to a considerable extent, on the condition of the central nervous system.