Multiple synchronous bilateral neoplasms of the parotid glands.

Abstract: In this paper we report the rare case of a patient who came to our attention with three synchronous Warthin tumours affecting both the right and left parotid glands. The patient was a 68-year-old female, heavy smoker, with a seven-year history of painless growing nodules in both pre-auricular areas. Left-sided subtotal parotidectomy and contralateral superficial parotidectomy were performed at two differ-ent surgical times. Multiple, simultaneous and bilateral Warthin tumours represent a rare pathological entity of the salivary glands. Careful preoperative examination and radiological evaluation of the salivary glands are critical for the early diagnosis of bilateral synchronous tumours.

Branchiogenic carcinoma with rapid growth and skin involvement: a case report.

ABSTRACT: Branchiogenic carcinoma (BC) is an extremely rare and still controversial clinic entity with few cases reported in literature. This malignant squamous epithelial wall degeneration of a pre-existing second branchial cleft cyst (SBCC) was first described by Von Volk-mann in 1882. Here we present a case of cervical cystic mass that was histologically diagnosed as a primary branchial cleft cyst carcinoma. This is the first documented cases of primary BC presenting with skin involvement on initial examination.

La arquitectura genética como herramienta de análisis del mapa genotipo-fenotipo / Genetic architecture as an analysis tool of the genotype-phenotype map

El estudio de la relación entre el genotipo y el fenotipo es de gran importancia para las investigaciones en genética y en las ciencias de la vida en general. A diferencia de la concepción tradicional de esta relación como un conjunto invariante de parámetros, el enfoque actual utiliza la arquitectura genética, una herramienta realista y dinámica que permite elucidar el mapa genotipo-fenotipo, ahora considerado una estructura en evolución. De las complejas relaciones entre los elementos del mapa genotipo-fenotipo surgen diversas propiedades emergentes que pueden explicar distintos fenómenos evolutivos. Además, algunas de estas propiedades promueven la acumulación de variabilidad genética en poblaciones naturales, la cual constituye el sustrato de procesos evolutivos como la selección natural. La caracterización y análisis de la arquitectura genética de caracteres adaptativos constituye una herramienta eficaz para comprender los procesos genéticos subyacentes al cambio evolutivo.

Studying the relationship between genotype and phenotype is of great importance for genetics and life science studies in general. In contrast with the traditional view of this relationship as an invariant set of parameters, the current approach incorporates the concept of genetic architecture, a realistic and dynamic tool that allows to elucidate the genotype-phenotype map, which is now regarded as an evolving structure. From the complex relationships between the elements in the genotype-phenotype map several emergent properties arise that can explain different evolutionary phenomena. Moreover, some of these properties promote the accumulation of genetic variability in natural populations, which constitutes the substrate to evolutionary processes such as natural selection. The characterization and analysis of the genetic architecture of adaptive traits constitutes a powerful tool to understand the genetics underpinnings of evolution.

Glutamate binding-site ligands of NMDA receptors.

Excitatory neurotransmission mediated by NMDA (N-methyl-D-aspartic acid) receptors plays a key role in both healthy and diseased processes in the brain. Therefore, bioactive compounds that can interact selectively with these receptors have been the aim of extensive research in the search of effective therapeutic agents or, at least, useful pharmacological tools. NMDA receptors are heteromeric ion channels that contain different modulatory sites capable to bind subunit-selective ligands. In particular, the activation of NMDA receptors requires two distinct ligands: glutamate (the endogenous agonist) and glycine (the co-agonist). In view of the renewed interest in this research area and the high therapeutic potential of this target, this review presents an updated survey of ligands which interact with the glutamate binding-site of the NMDA receptors, their rational development, and data on the structure-activity relationship which are of utmost importance for the design of novel lead compounds.

Use of pralidoxime without atropine in rivastigmine (carbamate) toxicity.

Some experimental models suggest that the use of pralidoxime in carbamate toxicity is deleterious. Although pretreatment with atropine minimizes the adverse effect of pralidoxime reported in these models, concerns over the risks of pralidoxime in humans with carbamate poisoning continue. We present a unique case of carbamate toxicity treated successfully with pralidoxime alone. An 80-year-old woman with Alzheimer's dementia presented to the emergency department with 3-4 days of lightheadedness, vomiting, diarrhea, and bilateral lower extremity muscle pain. Extensive review of systems was otherwise negative. Her vital signs were BP, 207/85 mmHg; pulse, 101 beats/min; rectal temperature, 36.6( degrees )C; respirations, 18/min; and SpO(2), 95% breathing room air. Her bedside glucose measurement was 6.7 mmol/L. Physical examination revealed a confused, diaphoretic, ill-appearing woman with miosis and fasciculations of the tongue, eyelids, gastrocnemius and quadriceps bilaterally. The heart, lung, abdominal and head, eyes, ears, nose and throat examinations were otherwise unremarkable. Nine 5-cm(2) rivastigmine patches (9.5 mg/24-hour) were found adherent to her torso and lower extremities. The patches were immediately removed and underlying skin cleansed with soap and water. Laboratory values including complete blood count, basic metabolic panel, calcium, magnesium, phosphorus, troponin, coagulation studies and urinalysis were unremarkable. Due to the absence of pulmonary muscarinic findings, no atropine was administered. However, 1 g of pralidoxime was administered intravenously over 30 min to treat fasciculations. Within 30 min of this treatment, there was significant improvement in symptoms and resolution of fasciculations. She was admitted to the hospital, required no further pralidoxime therapy and was discharged after 3 days. Rivastigmine is a reversible (carbamate) cholinesterase inhibitor used to treat dementia. In overdose, cholinergic crisis is expected and in this case was precipitated by patch overuse. We believe there was a causal relationship between pralidoxime administration and the prompt resolution of symptoms and fasciculations. This case of apparently safe and effective pralidoxime use without concomitant atropine administration in a patient with carbamate toxicity reinforces recent data demonstrating the potential safety of pralidoxime in carbamate toxicity.

Inconsistent approach to the treatment of chronic digoxin toxicity in the United States.

Evidence-based guidelines do not exist for the treatment of patients with chronic mild-moderate digoxin toxicity. We sought to evaluate differences among specialists in the use of digoxin-specific antibody fragments and the decision to admit these patients. A sample of cardiologists, emergency physicians, and medical toxicologists was surveyed. The survey detailed four hypothetical cases of chronic digoxin toxicity created by consensus among authors. All cases had the same digoxin concentration, but signs and symptoms varied in an attempt to explore four different thresholds. For each scenario, clinicians made decisions about admission and treatment. Survey response varied: cardiologists 17%, emergency physicians 6.7%, and toxicologists 39%. Statistically significant difference was found in the administration of Fab among cardiologists (67%), emergency physicians (82%), or toxicologists (91.5%) and admission rate (cardiologists 34%, emergency physicians 28%, and toxicologists 46%). Differences exist among clinicians of various specialties regarding treatment of chronic digoxin toxicity. These differences may reflect diverse perspectives or knowledge gaps and may translate into excess cost or less than ideal care. Exploring these differences may improve patient care, improve interactions among providers, and set the stage for development of consensus guidelines and research.

Degradation of 5-hydroxymethylfurfural in honey.

5-Hydroxymethylfurfural (HMF) is the most important intermediate product of the acid-catalyzed dehydration reaction of hexoses and/or Maillard reaction; furthermore, it is the most used index to evaluate thermal damages or ageing in food products. Usually its degradation reactions, being very slow, are neglected. This study reports the findings concerning the degradation kinetics of HMF, in honeys of different floral origin at a temperature between 25 and 50 degrees C. The results highlighted higher degradation rates (k(HMF) (degradation)) compared to the corresponding formation rates (k(HMF) (formation)) in chestnut and citrus samples. Similar k-values were found in multifloral honey. Moreover, the reaction of HMF degradation was characterized by lower activation energy (E(a)) values compared to E(a) formation values. The final concentration of HMF in honey, during storage at room temperature, should be ascribed to high sugar concentration. The fluctuation of HMF in honeys could depend on the equilibrium between the accumulation and the degradation processes. This can affect the validity of HMF as storage index in some honeys, above all during the analysis of those honeys whose legislation is too restrictive (citrus) or in chestnut honey analysis where it does not accumulate.

2-(2,6-Dihalophenyl)-3-(pyrimidin-2-yl)-1,3-thiazolidin-4-ones as non-nucleoside HIV-1 reverse transcriptase inhibitors.

Several 1,3-thiazolidin-4-ones bearing a 2,6-dihalophenyl group at C-2 and a substituted pyrimidin-2-yl ring at the N-3 were synthesised and evaluated as anti-HIV agents. The results of the in vitro tests showed that some of them were highly effective inhibitors of human immunodeficiency virus type-1 (HIV-1) replication at 10-40 nM concentrations with minimal cytotoxicity. Structure-activity relationship studies revealed that the nature of the substituents at the 2 and 3 positions of the thiazolidinone nucleus had a significant impact on the in vitro anti-HIV activity of this class of potent antiretroviral agents. The compounds had significantly reduced activity against the characteristic NNRTI-resistant virus mutants (bearing the K103N and Y181C RT mutations), thereby acting as non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors (NNRTIs).

Prevalence of oesophagitis in patients with persistent upper respiratory symptoms.

A growing body of evidence suggests that a variety of upper respiratory symptoms (URS) are associated with gastro-oesophageal reflux (GORD). The aim of this study was to determine the prevalence of endoscopic erosive, and non-erosive, oesophagitis among patients complaining of persistent URS, in the absence of typical GORD symptoms, and to compare them with a comparison group of similar age. A group of 110 patients aged 18-75, presenting with persistent URS with no suspicion of GORD symptoms, underwent upper flexible endoscopy, with biopsy sampling for histology, and was compared with a group of 117 patients of similar age undergoing endoscopy for reasons other than GORD. Patients affected with upper airway disorders, such as posterior laryngitis, chronic sinusitis and vocal fold nodules, had a significantly higher prevalence of oesophagitis of varying degrees (31 per cent) compared to the comparison population (15.4 per cent) (p < 0.01). These data suggest that in many patients with chronic URS occult gastro-oesophageal diseases are present.

Solid-phase microextraction and gas chromatography-mass spectrometry for rapid characterisation of semi-hard cheeses.

A headspace solid-phase microextraction (HS-SPME) method in combination with gas chromatography-mass spectrometry (GC-MS) has been used for extraction and identification of components of the volatile fraction of "Provola dei Nebrodi", a typical semi-hard Sicilian cheese. Cheese samples from different producers and at different ripening stages have been examined. The effects of various conditions (e.g. sample volume, sample headspace volume, sample heating temperature, extraction time, etc.) on extraction efficiency were studied in order to optimise the technique. The technique used made it possible to identify 61 components: fatty acids from C(2) to C(14) and their esters, aldehydes, alcohols, methyl ketones, delta-lactones, aromatic compounds, hydrocarbons and terpenes. The main components were butanoic, hexanoic and octanoic acids. The linear free fatty acids (FFA) from C(2) to C(10) were quantified by using the standard addition method. Calibration curves constructed for the FFA spiked into cheese were highly linear with a correlation coefficient R(2) > 0.998. Significant statistical differences (P> or =0.05) were evident for the even-carbon-number fatty acids during ripening.

Chromatographic determination of 7,8-methylenedioxy-4H-2,3-benzodiazepin-4-ones in rat plasma: relationship to their anticonvulsant activity.

The present investigation was designed to develop an assay suitable for pharmacokinetic studies of new compounds, i.e. the novel 7,8-methylenedioxy-4H-2,3-benzodiazepin-4-one derivatives (2a and 2b), acting as non-competitive AMPA-receptor antagonists. A reversed-phase high-performance liquid chromatographic method has been developed to determine the time-course of plasma concentrations of derivatives 2a and 2b administered intraperitoneally to Sprague-Dawley rats. The separation of compounds studied and a N-methyl-2,3-benzodiazepin-4-one derivative as internal standard (I.S.) from plasma, were carried out by liquid-liquid extraction using diethyl ether. The samples were injected onto the analytical column (Partisil 10 ODS) eluted with acetonitrile/0.01 M acetate buffer (pH 5.3) at a flow-rate of 2 ml/min and detected at 240 nm. Compounds 2a, 2b and I.S. gave retention times of 8.5, 5.25 and 11.1 min, respectively. The selectivity of the method was satisfactory. The mean recovery from spiked rat plasma ranged from 86.7 to 91.6% for 2a, and from 85.1 to 87.0% for 2b. The procedures were validated with a good reproducibility and linear response from 0.0625 to 2 microg/ml, with a regression coefficient of 0.9932 for 2a and 0.9854 for 2b. The lower limit of quantification (LOQ) was taken as 15 ng/ml for the two compounds. 2a and 2b showed no signs of significant degradation in rat plasma during storage at -20 degrees C and following freeze/thaw cycles. Moreover, plasma levels of the tested compounds have been correlated with their anticonvulsant activity, determined in vivo in genetically epilepsy-prone rats. Due to its sensitivity, the method was suitable for application to pharmacokinetic study.

[Postoperative pain in laparoscopic surgery]. / Il dolore post-operatorio in chirurgia laparoscopica.

The occurrence of post-operative pain, although less severe and frequent than in open surgery, may affect length of hospital stay and early return to normal activity in some patients operated on with laparoscopic surgery. Although several pathogenetic factors have been indicated in the literature, the mechanism responsible for post-operative pain after laparoscopy; still remains unclear. In this study the Authors evaluated post-operative pain in 90 patients submitted to laparoscopic cholecystectomy and correlated it to the length of operation, endoabdominal CO2 pressure maintained during surgery, and use of local anesthesia instilled din the liver bed and in the sites of introduction of trocars. Measuring post-operative pain by means of a modified Scott-Huskisson Visual Analogue Scale, no difference in the severity of the pain was noted in the two subgroups of patients with a length of operation inferior or superior to 60 minutes, respectively. Conversely, a statistical significant difference (p = 0.04 and p = 0.049 according to Fisher exact test and Pearson test, respectively) was observed evaluating the use of local anesthesia and the level of CO2 endoabdominal pressure, with less pain in patients whose pressure was maintained under 10 mmHg and in patients treated with instillation of local anesthetic drugs in the liver bed and in the sites of introduction of trocars.

4,5-Dihydro-7,8-dimethoxy-1-phenyl-3H-2,3-benzodiazepin-4-one.

The title compound, C(17)H(16)N(2)O(3), is an antagonist for AMPA/kainate receptors. The molecule has its seven-membered oxadiazole ring in a boat conformation. Asymmetry of the two methoxy bond angles is evident, with (Me)O-C-C angles of 115.45 (12) and 124.78 (13) degrees, and 114.67 (12) and 125.31 (12) degrees. A centrosymmetric dimer involving the HN-CO moieties, with an N...O distance of 2.876 (2) A, graph set R(2)(2)(8), is further linked into chains through methoxy Csp(3)-H...N hydrogen bonds, with a C...N distance of 3.418 (2) A.

Synthesis and antitumour activity of 1H,3H-thiazolo[3,4-a]benzimidazole derivatives.

A series of 1H,3H-thiazolo[3,4-a]benzimidazoles were synthesized and tested for their in vitro antitumour activity against 60 human tumour cell lines. Some derivatives exhibited both tumour growth inhibition activity and cellular selectivity. In particular, compound 8c, the most active of the series, was very active towards all cell lines at concentrations ranging from 10(-7)-10(-5) M. Compound 4a, on the other hand, was highly selective against the CNS cancer cell line.

Discovery of 2,3-diaryl-1,3-thiazolidin-4-ones as potent anti-HIV-1 agents.

Design, synthesis and anti-HIV activity of a series of 2,3-diaryl-1,3-thiazolidin-4-ones are reported. Some derivatives proved to be highly effective in inhibiting HIV-1 replication at nanomolar concentrations thereby acting as non-nucleoside HIV-1 RT inhibitors (NNRTIs). SAR studies evidenced that the nature of the substituents at the 2 and 3 positions of the thiazolidinone nucleus largely influenced the in vitro anti-HIV activity of this new class of potent antiviral agents.

7-Chloro-1-(2,6-difluorophenyl)-1H,3H-thiazolo.

The title molecules, C(15)H(9)ClF(2)N(2)S and C(16)H(12)F(2)N(2)S, respectively, display the well known butterfly-like conformation with a flat thiazolobenzimidazole system. In both compounds, the mean plane through the tricyclic system is almost perpendicular to the 2,6-difluorophenyl ring. This arrangement of the aryl group is determined by two intramolecular hydrogen bonds and by an attractive F.S interaction.

Synthesis and anticonvulsant activity of novel and potent 1-aryl-7,8-methylenedioxy-1,2,3,5-tetrahydro-4H-2,3-benzodiazepin-4-ones.

The synthesis and anticonvulsant activity of 1-aryl-7,8-methylenedioxy-1,2,3,5-tetrahydro-4H-2,3-benzodiazepin-4-(thi)ones (4a-d) and their 3-N-alkylcarbamoyl derivatives (4e-h) are reported. The new compounds possess marked anticonvulsant properties, comparable to those of the dehydro analogues 3 and higher than that of GYKI 52466 (1). Noteworthy, compound 4c shows a longer-lasting anticonvulsant activity. Electrophysiological experiments show that derivative 4c is less effective than 1 and 3c to reduce the KA-evoked currents in cerebellar granule neurons.

Synthesis and structure-activity relationships of 2,3-benzodiazepines as AMPA receptor antagonists.

There is increasing evidence of the potential therapeutic utility of glutamate receptor antagonists in the treatment of several neurodegenerative disorders, including stroke and epilepsy. In the last few years noncompetitive AMPA receptor antagonists have received considerable attention due to their therapeutic potentiality. The discovery of GYKI 52466, the prototype of noncompetitive AMPA receptor antagonists endowed with anticonvulsant and neuroprotective properties, induced growing interest on 2,3-benzodiazepine derivatives. This review covers the chemistry and pharmacology of this important class of AMPA receptor antagonists.

Synthesis, biological activity, pharmacokinetic properties and molecular modelling studies of novel 1H,3H-oxazolo[3,4-a]benzimidazoles: non-nucleoside HIV-1 reverse transcriptase inhibitors.

New 1H,3H-oxazolo[3,4-albenzimidazoles (OBZs) were synthesized as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTI) to extend the structure-activity relationships observed for an early series of related 1H,3H-thiazolo[3,4-a]benzimidazole derivatives (TBZs). The new compounds showed inhibitory activity against the replication of various HIV-1 strains, including NNRTI-resistant strains. Testing of a representative OBZ derivative in an HPLC assay on biological fluids, indicated that the sulphur substitution appreciably improved the metabolic stability of the TBZ compound. In addition, molecular modelling studies demonstrated that OBZs, TBZs and other NNRTIs have similar structural properties, that is a butterfly-like conformation, which is a key structural requirement for reverse transcriptase inhibition.

Synthesis and anticonvulsant properties of 2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-one derivatives.

A number of novel 1H-pyrrolo[1,2-a]benzimidazol-1-one derivatives were prepared and their anticonvulsant properties evaluated. The new synthesized compounds proved to possess anticonvulsant effects depending on the nature of substituents at C-6, C-2, and C-3a positions of the polycyclic system. In particular, the 6-chloro-3a-(p-tolyl)-2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-one derivative (22) displayed potency fivefold higher than unsubstituted compound (13).