Expression of a Constitutively Active Human Insulin Receptor in Hippocampal Neurons Does Not Alter VGCC Currents.

Memory and cognitive decline are the product of numerous physiological changes within the aging brain. Multiple theories have focused on the oxidative, calcium, cholinergic, vascular, and inflammation hypotheses of brain aging, with recent evidence suggesting that reductions in insulin signaling may also contribute. Specifically, a reduction in insulin receptor density and mRNA levels has been implicated, however, overcoming these changes remains a challenge. While increasing insulin receptor occupation has been successful in offsetting cognitive decline, alternative molecular approaches should be considered as they could bypass the need for brain insulin delivery. Moreover, this approach may be favorable to test the impact of continued insulin receptor signaling on neuronal function. Here we used hippocampal cultures infected with lentivirus with or without IRß, a constitutively active, truncated form of the human insulin receptor, to characterize the impact continued insulin receptor signaling on voltage-gated calcium channels. Infected cultures were harvested between DIV 13 and 17 (48 h after infection) for Western blot analysis on pAKT and AKT. These results were complemented with whole-cell patch-clamp recordings of individual pyramidal neurons starting 96 h post-infection. Results indicate that while a significant increase in neuronal pAKT/AKT ratio was seen at the time point tested, effects on voltage-gated calcium channels were not detected. These results suggest that there is a significant difference between constitutively active insulin receptors and the actions of insulin on an intact receptor, highlighting potential alternate mechanisms of neuronal insulin resistance and mode of activation.

The effect of pregabalin - codeine combination on partial sciatic nerve ligation - induced peripheral mononeuropathy in rats.

The present study investigates the effects of pregabalin (PGB) and codeine (COD) combination on neuropathic hyperalgesia in an animal model of peripheral nerve injury represented by partial sciatic nerve ligation. Hot plate and analgesimeter tests were performed to evaluate the influence of PGB, COD and their combination on thermal and mechanical hyperalgesia in the hind paw with partial sciatic nerve ligation. Reactivity was evaluated by measuring the latency to withdrawal of the operated hind paw from the noxious heat and pressure stimulation. Nociceptive thresholds were evaluated before (baseline) and in the 1(st), 3(rd), 5(th) and 7(th) day after surgical procedure. The investigation demonstrates that the treatment with PGB attenuated partial sciatic nerve ligation development of thermal and mechanical hyperalgesia in rats operated hind paw. The oral administration, during 14 consecutive days of PGB-COD combination significantly reduced the degree of both thermal and mechanical hyperalgesia in the hind paw with partial sciatic nerve ligation. These results suggest that the association of PGB with COD exerted ameliorative effect on partial sciatic nerve ligation-induced neuropathic pain in rats.

Electrical probe characteristic recovery by measuring only one time-dependent parameter.

Two straightforward methods for recovering the current-voltage characteristic of an electrical probe are proposed. Basically, they consist of replacing the usual power supply from the probe circuit with a capacitor which can be charged or discharged by the probe current drained from the plasma. The experiment requires the registration of only one time-dependent electrical parameter, either the probe current or the probe voltage. The corresponding time-dependence of the second parameter, the probe voltage, or the probe current, respectively, can be calculated using an integral or a differential relation and the current-voltage characteristic of the probe can be obtained.

Persistent repeated measurements by magnetic resonance spectroscopy demonstrate minimal hepatic encephalopathy: a case report.

Minimal Hepatic Encephalopathy (MHE), previously referred to as infraclinical or subclinical is a precursor in the development of clinical hepatic encephalopathy (HE). The demonstration of MHE is done through neuropsychological testing in the absence of clinical evidence of HE, patients showing only a mild cognitive impairment. Neuropsychological tests employed consist of Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and portosystemic encephalopathy (PSE) test score. Unfortunately, there are numerous occasions when the tests prove irrelevant: in the situation of inexperienced investigators, the patient's poor education, vision problems or concurring central nervous system disease, all of which may delay or deviate from the correct diagnosis.

EBV in pediatric neoplasia--intensity of infection as independent prognostic factor.

RATIONALE: Cancer disease is continuously rising worldwide as far as its incidence is concerned. Efforts were made in order to identify the etiologic factors. A good example for exogenous factors is Epstein Barr virus (EBV) which is largely spread worldwide, over 90% of the adult general population being infected by it. EBV is believed to be implicated in Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, etc. OBJECTIVE: In this paper, we will try to present the experience of two centers in Cluj County involved in the treatment of pediatric cancer, focusing on the influence of the presence of Epstein Barr virus in the outcome of the neoplasia. METHODS AND RESULTS: we took into account the clinical data regarding histology, stage of the disease, titer of specific antibodies for EBV, serological and imagistic evaluations of the patients treated in a retrospective consecutive manner for 5 years--2005-2010. Regarding our cohort of 120 patients, we analyzed the items in the paper in detail together with the statistical analysis and searched for a link between the intensity of the infection of EBV and response, disease, free survival, toxicities of the treatment. DISCUSSION: there are few data concerning the influence of EBV regarding the outcome of pediatric neoplasia. The published studies suggest a positive influence of EBV especially in Hodgkin disease mixed cellular subtype. In this study, EBV negative patients do better than the EBV positive, but the infection with EBV protects the patients against hematological toxicities.

Updates in MRI characterization of the thymus in myasthenic patients.

PURPOSE: To evaluate the imaging appearance of the thymus in the myasthenic patients by using chemical shift magnetic resonance imaging, and, to correlate the chemical shift ratio (CSR) with pathologic findings after surgical excision. MATERIALS AND METHODS: In the past year, a total of 11 myasthenic patients (4 males, 7 females; age range of 26-65 years), have been investigated by MRI centered at the thymic lodge. Our protocol included a Dual-Echo technique, T1-weighted In-phase/Opposed-phase MR images in all patients. A chemical shift ratio (CSR) was calculated by comparing the signal intensity of the thymus gland with that of the chest wall muscle for quantitative analysis. For this purpose, we have used standard region-of-interest electronic cursors at a slice level of the maximum axial surface of the thymus. We have identified two patients groups: a thymic hyperplasia group and a thymic tumoral group. RESULTS: With the decrease in the signal intensity of the thymus gland at chemical shift, the MR imaging was evident only in the hyperplasia group. The mean CSR in the hyperplasia group was considerably lower than that in the tumor group, 0,4964 ± 0,1841, compared with 1,0398 ± 0,0244. The difference in CSR between the hyperplasia and tumor groups was statistically significant (P=0,0028). CONCLUSION: MR imaging using T1-weighted In-phase/Opposed-phase images could be a useful diagnostic tool in the preoperative assessment of the thymic lodge and may help differentiate thymic hyperplasia from tumors of the thymus gland.

Skeletal and dentoalveolar changes in the maxillary bone morphology using two-arm maxillary expander.

OBJECTIVE: The purpose of this study was to evaluate the dental and skeletal changes in the maxillary bone morphology, produced by two-arm rapid palatal expansion appliances. PATIENTS AND METHODS: The study included 22 girls with an average age of 11.9 years treated with RPE appliances at the Department of Pedodontics and Orthodontics, Faculty of Dentistry, Timisoara, Romania. We evaluated the changes on study casts, using an optical 3D scanner--Activity 101 (SmartOptics) and also on radiographs. The level of statistical significance was set by comparing the changes between pre and post treatment values. We also used the Pearson's correlation coefficient (r) to measure the strength of the association between the recorded measurements. The correlations were significant at p<0.05. RESULTS: Significant changes were found in intermolar width change, interpremolar width change, molar tipping and alveolar tipping. Less significant changes were found in molar rotation and palatal depth change. After rapid maxillary expansion, five of the 21 correlations were found to be statistically significant. Positive medium correlations were found between intermolar width change and alveolar tipping and between interpremolar width change and alveolar tipping. A negative medium correlation was found between palatal depth change and alveolar tipping. Weak, but statistically significant correlations were found between intermolar width change and interpremolar width change and between intermolar width change and palatal depth change. No statistically significant correlation was found between the other variables. CONCLUSIONS: This type of maxillary expander is capable of expanding the maxillary dentition and alveolar process, opening the midpalatal suture and changing the maxillary bone morphology. The most remarkable changes occurred in the transverse plane. Future research is required to evaluate a larger group of patients.

Magnetic resonance spectroscopy--a non-invasive method in evaluating focal and diffuse central nervous system disease.

Magnetic Resonance Spectroscopy is a non-invasive method, which can be performed following a routine Magnetic Resonance investigation within the same examination, and can provide very useful molecular information related to the metabolism and function of the normal and pathological structures of the brain. Its role is increasing in the establishment of a clear diagnosis, in both focal and diffuse central nervous system diseases, and the tendency is to replace the histopathology test, in certain cases, with similar or sometimes better diagnostic accuracy. This paper summarizes the principle, method, and main clinical applications, standing as a guide to procedure performing and results interpretation.

The thymus in myasthenic patients: correlation between mediastinal CT imaging and histopathological findings.

PURPOSE: To correlate computed tomographic (CT) appearance of the thymus with results from histologic examination of thymic tissue in myasthenic patients who underwent thymectomy. MATERIALS AND METHODS: A retrospective study, based on case series report, between January 2000 and December 2010 on 247 patients with generalized myasthenia gravis or myasthenic syndrome explored by CT using a specific protocol, in the Radiology and Medical Imaging Department of Fundeni Clinical Institute. All subjects in the study were operated and had a histologic evaluation. RESULTS: CT examinations of these 247 subjects showed remaining thymic mass, remnant of thymic tissue, fatty infiltration of the thymus and tumoral thymus or focal thymic mass. The results of histologic examination showed normal thymus, thymic lymphoid follicular hyperplasia, thymic atrophy, fatty infiltration and thymoma. CONCLUSION: It was a 100% correlation between CT examinations and intra-operative findings regarding the presents of focal thymic masses in our study. In the diagnostic of focal thymic mass, the only inter-disciplinary correlation is between radiological and macroscopic aspects. CT examination has a limited value in differential diagnosis between thymic lymphoid follicular hyperplasia and thymoma.

Updates in CT characterization of thymic epithelial tumors in patients with myasthenia gravis.

Thymic epithelial tumors have been traditionally classified into two main types: noninvasive and invasive thymoma. Several classifications have been proposed for thymic tumors, but according to these classifications, the prognosis of patients with thymomas varies considerably. Our purpose is to present different CT aspects according to various subtypes of thymic epithelial neoplasms based on the simplified World Health Organization classification. In this article, we will discuss and illustrate histologic and functional features of the thymus and a spectrum of thymic tumors associated with Myasthenia Gravis. Smooth contours and a round shape are the most suggestive of type A thymic epithelial tumors, whereas irregular contours and heterogeneous enhancement are the most suggestive of type C tumors. Calcifications are suggestive of type B tumors. CT findings may serve as predictors of postoperative recurrence or metastasis for the thymic epithelial tumors.

Recurrent spontaneous pneumothorax in renal transplantation.

Renal transplantation could be associated with severe complications. Pneumothorax is a rare and severe complication among renal transplant recipients. The relationship between pneumothorax and post transplantation status, pulmonary infections or immunosuppressive treatment is controversial. We report the case of a young female with normal renal graft function who developed recurrent pneumothorax after three years of kidney graft.

Structure-activity correlations for illicit amphetamines using ANN and constitutional descriptors.

The goal of this study was to develop an expert system capable to identify the potential biological activity of new substances having a molecular structure similar to illicit amphetamines. For this purpose we have designed two types of artificial neural network (ANN) systems, which have been trained to classify amphetamines according to their toxicological activity (stimulant amphetamines or hallucinogenic amphetamines) and distinguish them from nonamphetamines. Such a system is essential for testing new molecular structures for epidemiological, clinical, and forensic purposes. The first type of artificial neural network is a "spectral" neural network, which has as input variables the most important 100 absorption intensities from a total of 260 measured for each normalized infrared spectrum 10cm(-1) apart. The spectral data consists of a database built with the GC-FT-IR spectra of the most popular drugs of abuse (mainly central stimulants, hallucinogens, sympathomimetic amines, narcotics and other potent analgesics), precursors and derivatized counterparts. All samples were also characterized by their constitutional descriptors (CDs). For each sample, a number of 45 CDs were computed and introduced as input variables for a second type of ANN, which uses a structural database. The efficiency of this "structural" artificial neural network (CD-ANN) has been improved by optimizing the training set and increasing the number of input variables (CDs). A comparative analysis of the spectral and the structural networks is presented.

[Efficacy of a combined Sabal-urtica preparation in the symptomatic treatment of benign prostatic hyperplasia. Results of a placebo-controlled double-blind study]. / Symptomatische Wirksamkeit eines Sabal-urtica-Kombinationspräparats in der Therapie des benignen Prostatasyndroms. Ergebnisse einer plazebokontrollierten Doppelblindstudie.

UNLABELLED: This re-evaluation of a double-blind placebo-controlled therapeutic study of the combined sabal-urtica preparation PRO 160/120 investigates the changes in the irritative symptoms of benign prostatic hyperplasia (BPH) under the test substance in comparison with placebo. It was found that, over the study period of 24 weeks, the micturition symptoms frequency and urgency were statistically significantly improved under the well-tolerated PRO 160/120 in comparison with placebo. The patient's quality of life was also significantly better under PRO 160/120 in comparison with placebo. CONCLUSION: The often distressing symptoms of BPH can be effectively ameliorated already after only a few weeks of treatment with the sabal-urtica preparation PRO 160/120. In particular those patients with the stigmatizing symptoms urinary urgency and frequency benefit from such treatment.

Hereditary motor and sensory neuropathy-russe: new autosomal recessive neuropathy in Balkan Gypsies.

A novel peripheral neuropathy of autosomal recessive inheritance has been identified in Balkan Gypsies and termed hereditary motor and sensory neuropathy-Russe (HMSN-R). We investigated 21 affected individuals from 10 families. Distal lower limb weakness began between the ages of 8 and 16 years, upper limb involvement beginning between 10 and 43 years, with an average of 22 years. This progressive disorder led to severe weakness of the lower limbs, generalized in the oldest subject (aged 57 years), and marked distal upper limb weakness. Prominent distal sensory loss involved all modalities, resulting in neuropathic joint degeneration in two instances. All patients showed foot deformity, and most showed hand deformity. Motor nerve conduction velocity was moderately reduced in the upper limbs but unobtainable in the legs. Sensory nerve action potentials were absent. There was loss of larger myelinated nerve fibers and profuse regenerative activity in the sural nerve. HMSN-R is a new form of autosomal recessive inherited HMSN caused by a single founder mutation in a 1 Mb interval on chromosome 10q.

Disseminated tuberculosis with gradual evolution and unusual localization.

We present a case of disseminated tuberculosis (pulmonary, skeletal and lymph nodes) accompanied by subcutaneous abscesses and with unusual localization, osteolytic lesions of the skull caused by Mycobacterium tuberculosis var. hominis. Although the patient was immunocompetent, the disease had a gradual and unexpected progression. In the malign forms of tuberculosis, treatment must be extended for a year or more.

[Clinical study of the efficacy of albendazole treatment in human hydatidosis]. / Studiu clinic al eficientei tratamentului cu albendazol în hidatidoza umana.

A follow-up study of Albendazol effectiveness therapy in human hydatid diseases was carry out using WHO methodology. Albendazole was given at a dose of 10 mg/Kg body/day in cycles of 28 days separated by 14 days without treatment. The efficacy of chemotherapy was evaluated by clinical improvement and changes in the cyst's morphology (detachment and collapse of the cyst membrane and increased density of the cyst fluid). We performed this study in 134 patients with hydatidosis: 17 patients with pre and post surgery treatment, 50 patients with post surgery treatment and 67 patients with chemotherapy only. Albendazole was effective in the hydatid disease; the patients with complex chemotherapy treatment did not report any secondary hydatidosis during the follow-up period (max. 2 years); the patients with exclusive chemotherapy reported 79% successful response, only 21% of them remained with unchanged cyst's size, but with modified internal structure. The therapeutic response depends of the cyst's size and its visceral site.

[Exudative uveitis, chronic labial herpes and interstitial pneumonia in an HIV-positive child]. / Uveita exsudativa, herpes labial cronic si pneumonie interstitiala la un copil HIV pozitiv.

The paper presents the case of a 6 and a half year-old child, with marked hipotrophy in height and weight (15 kg weight, which make a deficit of about 6 kg). The right eye presented pupilar sinekies, loaded vitreous and two white-yellow exsudative coroidal placards. One of them was inter-maculo-papilar having 4DP in diameter, difuse margins and aspect, the other was infero-macular. The right eye vision was only 2/50 n.c. The child also presented cronical labial herpes and interstitial pneumony. The ELISA test (+) confirmed the HIV suspicion. The paper insisted on the herpetical ethiology of the corio-retineal exsudative lesions.

Associated pathology with Wallenberg's syndrome. A report of three cases.

Three cases with Wallenberg's syndrome were reported, in which CT-scan revealed silent old right temporal infarction, right recent cerebellar haematoma and left calcified parietal subdural haematoma evidenced after 10 years since trauma due to a traffic accident. Although Wallenberg's syndrome constitutes a fully clinical diagnosis, CT-scan does not seem to be justified by the management logical deductions of the medical act; however, it is better to perform it in order to identify a possible associated pathology.