Search

Magnetic resonance imaging (MRI) is mandatory to identify the epileptogenic zone in refractory temporal lobe epilepsy (TLE). The correct identification of lesions is essential to obtain good post-surgery seizure control. Low grade tumours (LGT) and focal cortical dysplasia (FCD) are common findings in symptomatic TLE, and frequently coexist. The aim of this study was to identify the MRI characteristics in the diagnosis of FCD associated with LGT. We analyzed 24 subjects with TLE who underwent tailored surgery. They all had LGTs. Two expert neuroradiologists analyzed the imaging data and compared them with histological results, hypothesizing the causes of diagnostic errors in the identification of FCD. We selected three exemplary cases to report the most important causes of errors. In the diagnosis of FCD we reported false positives and false negatives due to different causes. An incomplete MRI protocol, the large dimensions of the tumour, infiltration and related oedema were the most important factors limiting MRI accuracy. MRI can be limited by an incomplete protocol. In addition, the presence of an LGT may limit the neuroradiological diagnosis of FCD in the temporal lobe. Advanced MRI techniques could help reveal subtle lesions that eluded a previous imaging inspection.

We report on three sibs who have autosomal recessive Clericuzio‐type poikiloderma neutropenia (PN) syndrome. Recently, this consanguineous family was reported and shown to be informative in identifying the C16orf57gene as the causative gene for this syndrome. Here we present the clinical data in detail. PN is a distinct and recognizable entity belonging to the group of poikiloderma syndromes among which Rothmund–Thomson is perhaps the best described and understood. PN is characterized by cutaneous poikiloderma, hyperkeratotic nails, generalized hyperkeratosis on palms and soles, neutropenia, short stature, and recurrent pulmonary infections. In order to delineate the phenotype of this rare genodermatosis, the clinical presentation together with the molecular investigations in our patients are reported and compared to those from the literature. © 2010 Wiley‐Liss, Inc.

Coenzyme Q10 (CoQ10, or ubiquinone) is an electron carrier of the mitochondrial respiratory chain (electron transport chain) with antioxidant properties. In view of the involvement of CoQ10 in oxidative phosphorylation and cellular antioxidant protection a deficiency in this quinone would be expected to contribute to disease pathophysiology by causing a failure in energy metabolism and antioxidant status. Indeed, a deficit in CoQ10 status has been determined in a number of neuromuscular and neurodegenerative disorders. Primary disorders of CoQ10 biosynthesis are potentially treatable conditions and therefore a high degree of clinical awareness about this condition is essential. A secondary loss of CoQ10 status following HMG-Coa reductase inhibitor (statins) treatment has been implicated in the pathophysiology of the myotoxicity associated with this pharmacotherapy. CoQ10 and its analogue, idebenone, have been widely used in the treatment of neurodegenerative and neuromuscular disorders. These compounds could potentially play a role in the treatment of mitochondrial disorders, Parkinsons disease, Huntingtons disease, amyotrophic lateral sclerosis, Friedreichs ataxia, and other conditions which have been linked to mitochondrial dysfunction. This article reviews the physiological roles of CoQ10, as well as the rationale and the role in clinical practice of CoQ10 supplementation in different neurological and muscular diseases, from primary CoQ10 deficiency to neurodegenerative disorders. We also briefly report a case of the myopathic form of CoQ10 deficiency.

The authors report the clinical and polygraphic features of rhythmic teeth grinding observed in a patient as the predominant symptom related to temporal lobe seizures during sleep and wakefulness. This observation demonstrates that exceptionally a teeth-grinding event can be not only a parasomnia (sleep bruxism) but also an epileptic-related motor event. Electromyographic and autonomic features of seizure-related teeth grinding support the interpretation of this motor phenomenon as a particular form of masticatory activity.

To clarify the mode of action of the vasoactive agent buflomedil, we evaluated plasma levels of adenosine and adenine nucleotides after intravenous (i.v.) infusion in humans of 50, 100, and 200 mg of the drug in 20 min. Buflomedil induced an increase of the same order of magnitude in plasma levels of adenosine and adenine nucleotides. Maximal adenosine increase (84) was observed at the end of the infusion period, whereas peak plasma levels of ATP and ADP (69 and 55, respectively) and of AMP (61) were detected 10 and 5 min after discontinuation of infusion, respectively. Although the exact mode of action of buflomedil at the molecular level remains unclear, some indirect findings suggest that the increase in adenosine may be due to enhanced release rather than to inhibition of cell uptake. Because such activity of buflomedil consists of enhancement of physiologic mechanisms of vasodilation and tissue protection occurring in the course of ischemic events, new pharmacologic perspectives for the drug may arise.

Cyclandelate, a vasoactive substance consisting of the mandelic acid ester of 3,3,5-trimethylcyclohexanol, was administered to 10 patients with cerebrovascular and/or peripheral vascular disease. Blood specimens were collected at 1 − 6 h after oral administration of 1600 mg cyclandelate, and the ester and acid were extracted from plasma in acid medium using n-hexane/isopropyl alcohol. The concentrations were determined by a high-performance liquid chromatography isocratic system. The highest plasma cyclandelate concentrations were detected at the third hour, whereas plasma mandelic acid concentrations were still increasing 6 h after administration.

The behaviour of the complement and of its components C4 and C3 has been studied in serum and in blister fluid both in patients with pemphigus vulgaris and other bullous dermatoses and in healthy subjects with experimentally induced blisters.

In 6 normal volunteers given single oral doses of 250, 500 and 1000 mg ticlopidine (T), the peak plasma level of unchanged drug was reached after about 2 h. There was no correlation between the plasma T level and its inhibitory effect on platelet function, expressed as % inhibition of ADP-induced aggregation. By means of HPLC and GC/MS significant concentrations of T were demonstrated in washed red cells, platelets and neutrophils, with a marked difference in the time course of the appearance of cell-associated drug. The time course of platelet-associated T very accurately fitted that of the antiaggregatory activity.

The interaction of levamisole and/or adenosine in vitro an E-rosette forming cells (RFC) of healthy subjects and on low RFC of patients affected with various diseases was investigated. Levamisole did not enhance normal RFC. The drug enhanced low RFC in some patients (responders) but not in others (non-responders). Adenosine inhibited normal and low RFC and this inhibition could be reversed by levamisole.Further, levamisole 150 mg 2 days a week was given to 12 Hodgkin's disease (HD) responders for 2 weeks, then 150 mg 1 day weekly for 2 1/2 months After one week of treatment RFC increased and the enhancement could be maintained during the whole treatment period.Lastly levamisole in vitro and in vivo diminished serum adenosine deaminase activity in normal subjects and HD patients.

The murine lymphomacrophage hybrids ESb, EbF1, EbF2-c4, which express c -fesconstitutively, were found by Southern analysis to bear a c -fesdeletion of almost 100 bp. The deleted allele was transmitted to the metastatic hybrids by their nonexpressing, poorly metastatic T-lymphoma progenitor Eb, which also has a structurally normal c -fesallele. PCR amplification and sequencing of fescDNA spanning exons 3–5, where the deletion mapped, ruled out any involvement of coding sequences in the rearrangement. PCR amplification of the as yet unsequenced murine c -fesIVS3 and IVS4 showed they are about 50% longer than their human and feline homologs. Sequencing of IVS4 showed no difference between tumor and control DNA. Sequencing of part of the ~2600-bp IVS3 was guided by the restriction analysis of PCR products from control and hybrid DNAs. This showed that differences from the control appeared to be mainly located in the 900-bp HindIII-EcoRI fragment, localized in the middle of IVS3. As all three hybrids had the same restriction map, this fragment was sequenced in one of them (ESb). A run of >200 CA repeats was found in control DNA, and a reduction in the CAnmicrosatellite accounted for most of the c-fesdeletion in the ESb hybrid. Interestingly, the 50% reduction in the size of human and feline c -fesIVS3 as compared with the murine homolog is mostly due to contraction of the same microsatellite.

The effect of i.v. infusion of adenosine (20/μg/kg/min over 10 min + 40/μg/kg/min over 10 min) on peripheral haemodynamics, blood rheology and platelet aggregation has been studied in 8 volunteers. Blood pressure, heart rate, rest flow at the lower limbs, blood viscosity, whole blood filterability, haemoglobin affinity for O2(P50), 2,3-diphosphoglycerate (2,3-DPG), platelet aggregation were measured. Free cytosolic calcium levels were evaluated in platelets in resting conditions and after in vitro stimulation. Plasma adenosine levels were detected by HPLC. Adenosine infusion did not induce significant changes in rest flow, blood pressure and heart rate. At the end of infusion a significant reduction in blood viscosity (p<0.01) with a concomitant significant increase of blood filterability (p<0.05) was observed. P50and 2,3-DPG tended to increase at the end of infusion as an expression of reduced haemoglobin affinity for O2potentially associated to an increased delivery of O2to peripheral tissues. Adenosine induced a significant reduction of platelet aggregability (p<0.01) with a decrease of free cytosolic calcium levels.In conclusion adenosine induces a series of biological changes possibly useful at the microcirculatory level at infusion rates that are well tolerated and devoid of significant haemodynamic effect.

Summary: In order to define the pharmacodynamic profile of salmon calcitonin (sCT) in humans, several markers of the biological activity of the drug have been studied, namely cAMP, adenosine and pO2 in venous blood, and the cytosolic free calcium level in circulating cells. Different dosages and routes of administration (1.5 IU. kg−1 and 0.75 IU kg−1 IM, and 1.5 IU. kg−1 via nasal spray) were compared. sCT caused an increase in cAMP, adenosine and pO2, and a decrease in cytosolic free calcium in neutrophils, lymphocytes and platelets. The peak times of all these parameters ranged between 109 and 182 min, and 101 and 168 min after IM and nasal spray administration respectively. There was greater variability in the values after IM than nasal spray of administration of sCT. It is concluded that adenosine and p02 in venous blood, and cytosolic free calcium in circulating cells are valuable markers of the activity of sCT and that sCT decreases the cytosolic free calcium level in neutrophils, lymphocytes and platelets. Pharmacodynamic analysis of the biological effects of the drug is highly reliable and valuable in predicting its pharmacological profile. sCT administration via a nasal spray is able to produce significant biological effects, although they are less marked than after IM dosing.

In the past few years there has been increasing interest in the role of the vascular endothelium as an active modulator of biological responses. Endothelial cells exert antithrombotic activity by the release of prostacyclin [23] and adenine nucleotides [16], the availability on the cell surface of heparin-like substances [3], and thrombomodulin-mediated activation of protein C [8]. In addition, endothelium is involved in the regulation of fibrinolysis by releasing soluble factors, such as tissue plasminogen activator (tPA; [10]) and plasminogen activator inhibitor (PAI; [22, 11]), as well as in the control of vascular responsiveness by the production of smooth muscle relaxing and contracting factors. Endothelial cells have also been shown to synthesize and to express procoagulant activities [18].

Directin situRTPCR has been successfully applied to paraffin-embedded human placental specimens. The expression of stem cell factor (SCF) mRNA visualized in cytotrophoblast and stromal cells is validated by the lack of any specific signal in parallel specimens where reverse transcription is omitted.

Intrauterine growth retardation and multiple malformations ascertained by echography allowed prenatal diagnosis of penta X syndrome at the 35th week of gestation. The proband's phenotype at birth was consistent with the antenatal observations and the clinical phenotype described in previous patients. The main clinical features were somatic hypodevelopment as compared to gestational age, craniofacial anomalies, congenital heart defects, and agenesia of the right kidney and ureter. Analysis of X-linked RFLPs in the parents and the proband allowed the maternal origin of the three extra X chromosomes to be established, suggesting consecutive nondisjunction events: one in meiosis I and the second, involving both X chromosomes, in meiosis II. Neither maternal age nor familial recurrence of chromosomal aneuploidies was a predisposing cause for the sequential nondisjunction in this case.

Abstract—Carbon dioxide inhibits phorogenesis in Phycomycesas does a gas produced by Phycomyces.We have isolated mutants which are supersensitive (B451, B452) or resistant (B455, B457) to the gas. These mutants are also supersensitive or resistant to CO2. We conclude that the gas is CO2. A pulse of blue, but not red, light overcomes this inhibition. The CO2sensitive step is completed 5–10 h before the appearance of visible sporangiophore initials.

The plasma kinetics of adenosine was investigated in healthy volunteers after a 1 minute infusion of 2.5, 5 and 10 mg (38, 79 and 148 µg·kg-1 respectively) and after infusion of 200 µg·kg-1 in 10 min followed by 400 µg·kg-1 in 10 min.

Aim: In the present study, we have evaluated whether physical exercise affect low osteocalcin concentrations observed in patients with subclinical hypercortisolism. Subjects and methods: Sixteen patients (10 men and 6 women, age 38–55 yr) with adrenal incidentaloma were studied. Fifteen healthy volunteers matched for age (range 35–47 yr) were used as controls. Subjects were submitted to a 8-week exercise-training program with cycle-ergometer for 1 h/day 3–4 days/week at 60% of their individual VO2 max. Before and after this period, resting venous serum osteocalcin and GH concentrations were measured in the same batch. The blood sampling after 8 weeks of the training program were performed after resting for one day. All patients and controls underwent also the following endocrine evaluation: serum cortisol, plasma ACTH. Results: Our results demonstrate a significant increase of osteocalcin after physical exercise and a positive correlation between osteocalcin and GH. This later might suggest a role of GH in the increased osteocalcin secretion. Conclusions: The data of the present study suggest a positive effect of physical exercise on bone metabolism in patients with adrenal incidentaloma.