Transdermal donepezil on the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is the most common type of senile dementia, characterized by cognitive deficits related to degeneration of cholinergic neurons. The first anti-Alzheimer drugs approved by the Food and Drug Administration were the cholinesterase inhibitors (ChEIs), which are capable of improving cholinergic neurotransmission by inhibiting acetylcholinesterase. The most common ChEIs used to treat cognitive symptoms in mild to moderate AD are rivastigmine, galantamine, and donepezil.

A case of congenital hypothyroidism in PHACE syndrome.

Although hemangiomas, benign tumors of vascular origin, are very common among children and represent the most frequent benign tumor at that age, their association with other malformations constitutes a rare neurocutaneous disorder called PHACE syndrome. This condition is characterized by posterior fossa anomalies, hemangioma of the face, arterial alterations, cardiac defects, and eye anomalies (as represented by the acronym PHACE); sternum defects, endocrinopathies, and thyreopathies may be present as well. In this report, we describe a case of congenital hypothyroidism due to an empty thyroid site, as demonstrated by ultrasound, in an Italian child.

Sanger sequencing in routine KRAS testing: a review of 1720 cases from a pathologist's perspective.

Background: Sanger sequencing (SS) of PCR products is still the most frequent method to test colorectal cancer for KRAS mutations in routine practice.

Methods: An audit of SS on 1720 routine cases was carried out, taking into account age, gender, specimen type (resection vs biopsies), tumour site (primary vs metastasis), tumour stage, neoplastic cells abundance (>30% vs <30%) and fixation type (buffered formalin vs simple formalin). In a subset of 50 wild-type (WT) patients correlations between SS findings and response rate (RR), progression-free survival (PFS) and overall survival (OS) were also evaluated.

Pressor response to oral tyramine and monoamine oxidase inhibition during treatment with ralfinamide (NW-1029).

Ralfinamide, an original Na(+) channel blocker developed for the treatment of chronic pain, inhibits monoamineoxidase-B with no apparent effect on monoamineoxidase-A. To evaluate the pressor response to oral tyramine under fasting conditions during treatment with ralfinamide in healthy normotensive subjects. Ten women and 10 men aged 52.

pPKCα-mediated effect on in vitro Aβ production in response to gamma secretase inhibitor LY411575 in rat CTXTNA2 astrocytes.

Alzheimer's Disease implies memory and cognitive impairment due to beta amyloid accumulation, presence of reactive microglia and astrocytes, loss of synapses, neural network dysfunctions and modifications of neuronal signalling. A key role in such events is played by astrocytes, which actively secrete high levels of beta amyloid protein originating from sequential cleavage of APP by alpha, beta and gamma secretases. Since inhibition of such process could represent an important strategy against the occurrence of Alzheimer's Disease, in this paper the role played by pPKC alpha in the in vitro beta amyloid production in response to gamma secretase inhibitor in rat cortical astrocytes is reported.

KRAS mutation detection by high-resolution melting analysis significantly predicts clinical benefit of cetuximab in metastatic colorectal cancer.

Background: Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies are restricted to KRAS wild-type (WT) metastatic colorectal cancers (mCRCs), usually identified by direct sequencing, that may yield false negative results because of genetic heterogeneity within the tumour. We evaluated the efficiency of high-resolution melting analysis (HRMA) in identifying KRAS-mutant (MUT) tumours.

Methods: We considered 50 mCRC patients scored as KRAS-WT by direct sequencing and treated with cetuximab-containing chemotherapy, and tested the correlations between HRMA findings and response rate (RR), progression-free (PFS) and overall survival (OS).

Comparison of two entry methods for laparoscopic port entry: technical point of view.

Laparoscopic entry is a blind procedure and it often represents a problem for all the related complications. In the last three decades, rapid advances in laparoscopic surgery have made it an invaluable part of general surgery, but there remains no clear consensus on an optimal method of entry into the peritoneal cavity. The aim of this paper is to focus on the evolution of two used methods of entry into the peritoneal cavity in laparoscopic surgery.

Facial nerve schwannoma involving middle cranial fossa: when the unilateral sensorineural hearing loss guide to the correct diagnosis.

The Facial Nerve Schwannoma is a rare tumor and it seldom involved the middle cranial fossa. Facial nerve schwannoma has various manifestations, including facial palsy but unfortunately facial nerve is very resistant to compression and often facial nerve paralysis or a facial weakness are not present. We present a case of giant facial nerve schwannoma involved the middle cranial fossa without facial nerve paralysis.

Synthesis of novel 4-aryl-1,2,3,4-tetrahydroisoquinolines as probes for dopamine receptor ligands.

Dopamine (DA) agonists, bearing catechol or phenol rings, are endowed with low oral bioavailability and short effect duration. In this report, the synthesis of novel differently substituted 4-(3-pyridyl)-1,2,3,4-tetrahydroisoquinolines and (1,2,3,4-tetrahydroisoquinolin-4-yl)phenylmethanols as potential non phenolic and non catecholic DA receptor ligands is reported. The new compounds, evaluated by binding tests on cerebral striatal membranes, bound to DA receptors with moderate affinity.

Exhaled nitric oxide is related to bronchial eosinophilia and airway hyperresponsiveness to bradykinin in allergen-induced asthma exacerbation.

Exhaled nitric oxide (FeNO) has been associated with bronchial eosinophilia and with airway hyperresponsiveness (AHR) in mild stable asthma. We previously demonstrated in a large project that allergen exposure is able to raise FeNO and to worsen AHR to bradykinin. We postulated that allergen-induced increase in FeNO could be related to heightened mucosal eosinophils and AHR to bradykinin in atopic asthma.

Vertigo in childhood: a methodological approach.

Children complaints dizziness merit meticulous evaluation to differentially diagnose a vestibular disease. A syndrome mimicking certain classic signs and symptoms of adult vestibular disorders may be presents in children, such as benign paroxysmal positional vertigo, usually associated with aging. Benign paroxysmal vertigo, in which migraine is a manifestation, with sudden onset of dizziness is a rare peripheral vestibular disorder that is commonly ignored or misdiagnosed.

Biomarkers in heart failure.

The meaning of the term biomarker has been standardized by a working group of the National Institutes of Health as "a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention". The ability of a biomarker to enhance the quality and efficacy of clinical care depends on several factors, including pretest probability, sensitivity and specificity, costs, benefits, risks, and even patient preference and alternatives. With the aim to better diagnose the multifactorial and complex syndrome of heart failure, research has led to discover many categories of potential pathophysiologic biomarkers for this debilitating disease.

Designing prodrugs for the treatment of Parkinson's disease.

Introduction: Current Parkinson's disease (PD) therapy is essentially symptomatic, and l-Dopa (LD), is the treatment of choice in more advanced stages of the disease. However, motor complications often develop after long-term treatment, and at this point physicians usually prescribe adjuvant therapy with other classes of antiparkinsonian drugs, including dopamine (DA) agonists, catechol-O-methyl transferase (COMT) or monoamine oxidase (MAO)-B inhibitors. In order to improve bioavailability, the prodrug approach appeared to be the most promising, and some antiparkinsonian prodrugs have been prepared in an effort to solve these problems.

Comparison of nerve content in removed parametrial tissue after classic radical hysterectomy and nerve-sparing radical hysterectomy--histologic evaluation.

Purpose Of Investigation: The aim of this study was to find whether nerve-sparing radical hysterectomy resulted in a lower amount of nerves in the removed parametrial tissue.

Methods: Histological specimens from nerve-sparing radical hysterectomy (28 cases) were compared with those obtained after classic radical hysterectomy (26 cases). Width of the parametria and vaginal cuff were measured.

Primary hepatic lymphoma in a patient with previous rectal adenocarcinoma: a case report and discussion of etiopathogenesis and diagnostic tools.

Primary hepatic lymphoma is an extremely rare malignancy accounting for 0.016% of all cases of non-Hodgkin lymphomas. Approximately 1-4% of histologies described show a follicular pattern.

Comparison of repositioning maneuvers for benign paroxysmal positional vertigo of posterior semicircular canal: advantages of hybrid maneuver.

Objective: The prevalence of benign paroxysmal positional vertigo (BPPV) is becoming more frequent in elderly population. The presence of comorbid factors has to be considered before assessment as well as before commencing any repositioning treatment. Our aims were evaluation of the maneuvers efficacy and evaluation of the applicability of hybrid maneuver (HM) in patients with physical limitation.

Central nervous system lymphoma occurring in a patient with neurofibromatosis type 1 (von Recklinghausen disease).

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder, which confers an increased risk of a wide range of cancers, and malignant tumors are the most common cause of death in individuals with NF1. Although in children with NF1, the most common neoplasms are optic nerve gliomas and brain tumors, an elevated risk of myeloid leukemia and an increased relative risk of acute lymphoblastic leukemia and non-Hodgkin lymphoma were reported. In adults with NF1, the relative risk of brain tumor is 100 times higher than in the general population.

An ELIME assay for the rapid diagnosis of coeliac disease.

Coeliac disease (CD) is a gluten-induced autoimmune enteropathy found in genetically susceptible subjects. Because of the high number of undetected cases, rapid and cheaper screening methods are needed. Currently, the CD diagnosis involves the detection of anti-transglutaminase IgA antibodies (anti-tTG IgA) in blood serum through the use of ELISA systems with confirmation by histology of the intestinal mucosa.

A specific miRNA signature correlates with complete pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

Purpose: MicroRNAs (miRNAs) are small, noncoding RNA molecules that can be down- or upregulated in colorectal cancer and have been associated to prognosis and response to treatment. We studied miRNA expression in tumor biopsies of patients with rectal cancer to identify a specific "signature" correlating with pathological complete response (pCR) after neoadjuvant chemoradiotherapy.

Methods And Materials: A total of 38 T3-4/N+ rectal cancer patients received capecitabine-oxaliplatin and radiotherapy followed by surgery.

Convergent sets of data from in vivo and in vitro methods point to an active role of Hsp60 in chronic obstructive pulmonary disease pathogenesis.

Background: It is increasingly clear that some heat shock proteins (Hsps) play a role in inflammation. Here, we report results showing participation of Hsp60 in the pathogenesis of chronic obstructive pulmonary diseases (COPD), as indicated by data from both in vivo and in vitro analyses.

Methods And Results: Bronchial biopsies from patients with stable COPD, smoker controls with normal lung function, and non-smoker controls were studied.

Gender-based blood transcriptomes and interactomes in multiple sclerosis: involvement of SP1 dependent gene transcription.

In this study we investigated the contribution of gender to global gene expression in peripheral blood mononuclear cells from multiple sclerosis (MS) patients and healthy controls. We observed that, in contrast to the conventional approach, gender-based case-control comparisons resulted in genelists with significantly reduced heterogeneity in human populations. In addition, MS was characterized by significant changes both in the quantity and in the quality of the sex-specific genes.

Methylene blue MMX tablets for chromoendoscopy. Safety tolerability and bioavailability in healthy volunteers.

Methylene blue-MMX tablets are proposed as colonic diagnostic staining. Methylene blue taken prior to colonoscopy is expected to provide an effective staining of colonic and rectal mucosa leaving unstained the dysplastic or polypoid areas. The present single dose, open-label study investigated the safety of methylene blue after single oral doses of 200 and 400mg in healthy volunteers.

L-Dopa prodrugs: an overview of trends for improving Parkinson's disease treatment.

L-Dopa is the mainstay of Parkinson's disease therapy; this drug is usually administered orally, but it is extensively metabolized in the gastrointestinal tract, so that relatively little arrives in the bloodstream as intact L-Dopa. The peripheral conversion of L-Dopa by amino acid decarboxylase to dopamine is responsible for the typical gastrointestinal and cardiovascular side effects. To minimize the conversion to dopamine outside the central nervous system, L-Dopa is usually given in combination with peripheral inhibitors of amino acid decarboxylase.

Capillary haemangioma of the middle ear: a rare lesion difficult to evaluate.

Haemangiomas are benign vascular tumours relatively common in the head and neck district but very rare in the temporal bone. Depending on its clinical presentation, haemangioma can be mistaken for other vascular masses such as glomus tumour or other lesions of the middle ear. Unfortunately, clinical and radiological evaluation may be insufficient to make a pre-operative diagnosis and the diagnosis is often based upon intra-operative biopsy specimen findings.