IGF-I induced rapid recruitment of integrin beta1 to lipid rafts is Caveolin-1 dependent.

Caveolin-1 (Cav-1) regulates both insulin like growth factor receptor (IGF-IR) and integrin beta1 function. However, the role of Cav-1 in IGF-IR/integrin beta1 cross talk remains to be established. In this study, we observed that IGF-I did not induce integrin beta1 internalization but its plasma membrane reorganization. In particular, we found a rapid and transient association between integrin beta1 and Cav-1 followed by the enrichment of integrin beta1 in lipid rafts. To determine the role of Cav-1 in this process, we transfected Hacat cells with small interfering RNA specific for Cav-1 (siRNA-Cav-1) and with a scrambled siRNA as control (siRNA-Ctr). Cav-1 down regulated Hacat cells were then stimulated with IGF-I and analyzed by immunofluorescence and flow cytometry. We found that Cav-1 silencing abolished the recruitment of integrin beta1 to lipid rafts in the presence of IGF-I. These data demonstrate that IGF-IR/integrin beta1 cross talk is followed by integrin beta1 lipid raft compartmentalization and that Cav-1 is required for this process.

Degree of catecholamine hypersecretion is the most important determinant of intra-operative hemodynamic outcomes in pheochromocytoma.

Pheochromocytoma resection is often complicated by intra-operative hypertension and post-resection hypotension. Factors associated with these hemodynamic alterations are not well defined. The aim of this study was to analyse the clinical-laboratory features associated with hemodynamic parameters during pheochromocytoma resection. Twenty-seven patients submitted to tumor resection - either open (no.=18) or video laparoscopic - between 1978-2007 were included. Nineteen received pre-operative alpha-blockers. Intra-operative hemodynamic data analysed were: maximum and minimum mean arterial blood pressure (MABP), no. of severe hypertensive (systolic BP >200 mmHg) and hypotensive episodes (MABP <60 mmHg), maximum and minimum heart rate (HR), no. of episodes of tachycardia and bradycardia, need to receive iv intra-operative treatment for hypertension and hypotension and the volume of fluids administered during surgery. Patients were 39.4+/-14.4-yr-old, 66% women. Intra-operative hemodynamic parameters were not different in patients submitted to open or video laparoscopic resection. Maximum intraoperative HR and the percentage of patients with HR>100 beats/min were higher in patients without pre-operative alpha- blocker treatment (no.=8). Pre-operative urinary vanylmandelic acid was positively associated with intra-operative maximum MABP (r=0.535, p=0.047) and with maximum transoperative systolic BP (r=0.805, p=0.016). Pre-operative urinary catecholamine (Pearson correlation r=0.575, p=0.03) and vanylmandelic acid (Pearson correlation r=0.605, p=0.04) levels were associated with maximum intra- operative MABP, adjusted for the presence of pheochromocytoma symptoms, surgical approach and pre-operative alpha-blockers. In conclusion, the degree of pre-operative catecholamine secretion was the most important aspect of transoperative BP control.

The Application of Chironomid Pupal Exuvial Technique (CPET) for Ecological Analysis in a Neotropical Large River System.

This field ecological study, based on the chironomid pupal exuvial technique (CPET), is new for the Paraná River and proposes an efficient tool to be used in future ecological approaches and biomonitoring. Drifting of pupal exuviae in a river-floodplain system of the Middle Paraná River floodplain was represented by 34 Chironomidae taxa, being the characteristic association obtained from the CPET: Lopescladius, Onconeura, Paralauterborniella, Polypedilum, and Harnischia complex. Diversity, richness, dominance, total density, and density of dominant taxa were different between the longitudinal and lateral dimensions but not between hydrologic phases, with a greater diversity and richness in the main channel of the river and higher density and dominance in floodplain habitats. The species turnover is the dominant process in structuring studied assemblages in spatial and temporal analysis, increasing in the floodplain habitats and in low-water phase. The results obtained showed that drifting exuviae in the longitudinal axis were coming from different assemblages and environments of a wider area (regional), while exuviae recorded in the connections of the floodplain environments in the lateral dimension could reflect the local assemblages. We demonstrated the ecological value of CPET studies to interpret the attributes of Chironomidae assemblage in river-floodplain systems of large rivers in an integrated way.

The Cricotopus (Oliveiriella) (Diptera: Chironomidae) of the High Altitude Andean Streams, with Description of a New Species, C. (O.) rieradevallae.

The genus Oliveiriella (Chironomidae, Orthocladiinae) was erected by Wiedenbrug & Fittkau (1997). The adults have characteristic black spots on their wings and other characteristics similar to the genus Cricotopus. Pupal skins are very characteristic with strong short spines in the anal lobe instead of setae, while larvae are distinguishable by the long anal papillae and the intense blue color of their body. However, Andersen et al (2013) consider Oliveiriella as a subgenera of Cricotopus. In this paper, using the sequences of the cox1 gene, we conclude that Oliveiriella should be considered a subgenus within Cricotopus, confirming its status in Andersen et al (2013). Furthermore, we describe Cricotopus (Oliveiriella) rieradevallae Prat & Paggi sp. n. from the Saltana river (Ecuador). The adult males, females, and preimaginal stages of the two species of subgenus Oliveiriella known from South America Cricotopus (O.) almeidai n. comb. from Peru, Brazil, and Argentina and Cricotopus (O.) sanjavieri n. comb. from Argentina are compared with those of Cricotopus (O.) rieradevallae sp. n. from Ecuador. The differences allow the distinction of the three species. The cox1 gene reveals that at least three different undescribed species of the same subgenus are present in the high-altitude tropical Andes. The morphology of the available pupae and pupal exuviae reveals the presence of several morphotypes that are candidates to be described as new species. A key used to distinguish these pupal morphotypes is provided, including the three described species. Additionally, the distribution of the subgenus is discussed.

The receiver operating characteristics curve in the evaluation of a random urine specimen as a screening test for diabetic nephropathy.

OBJECTIVE: To assess the performance of measurements of urinary albumin concentration (UAC) and urinary albumin:creatinine ratio (UACR) in a diurnal random urine specimen (RUS) for the screening of diabetic nephropathy. RESEARCH DESIGN AND METHODS: A total of 95 ambulatory NIDDM patients (49 women, ages 40-75 years) collected 123 RUSs during the morning after completing a timed 24-h urine collection. Albumin was measured by immunoturbidimetry. According to timed urinary albumin excretion rate (UAER) measured in the 24-h collection (criterion standard), samples were classified as normoalbuminuric (UAER < 20 micrograms/min; n = 54), microalbuminuric (UAER 20-200 micrograms/min; n = 44), and macroalbuminuric (UAER > 200 micrograms/min; n = 25). The receiver operating characteristics (ROC) curve approach was used. The ROC curves of UAC and UACR in RUS for screening of microalbuminuria (normo- and microalbuminuric samples; n = 98) and macroalbuminuria (micro- and macroalbuminuric samples; n = 69) were plotted. RESULTS: Spearman's coefficients of correlation of 24-h UAER vs. UAC and UACR were 0.91 and 0.92, respectively (P < 0.001). The calculated areas (+/- SE) under the ROC curves to screen microalbuminuria for UAC (0.9766 +/- 0.015) and UACR (0.9689 +/- 0.014) were similar (P > 0.05) as were the corresponding areas for macroalbuminuria (0.9868 +/- 0.0094 and 0.9614 +/- 0.0241, respectively; P > 0.05). The first point with 100% sensitivity and the point of intersection with a 100%-to-100% diagonal for microalbuminuria were as follows: 16.9 and 33.6 mg/l for UAC and 15.0 and 26.8 mg/g for UACR; for macroalbuminuria 174.0 and 296.2 mg/l for UAC and 116.0 and 334.3 mg/g for UACR, respectively. CONCLUSIONS: Albumin measurements (UAC and UACR) in an RUS presented almost perfect accuracy for the screening of micro- and macroalbuminuria and UAC measured in an RUS is simpler and less expensive than UACR and UAER. It is suggested as a valid test for use in screening for diabetic nephropathy.

Further studies on acid phosphatase in obese subjects.

Low activity genetic variants of acid phosphatase (ACP1) are positively associated with extreme body mass deviations in obese subjects. The same pattern has been found in non-diabetic children, in diabetic pregnant women, and in non-diabetic adult subjects. Low activity variants of ACP1 also show a positive association with family history of obesity, supporting the hypothesis of an enhancing action of these variants on expressivity of obesity.

Twenty-four-hour pattern of hunger sensation in obesity complicated by type 2 diabetes mellitus: a pattern recognition by spectral analysis.

Hunger sensation (HS) in humans physiologically shows intraday (circadian) and within-day (ultradian) recursivity. This intrinsic periodicity was investigated by applying the cosinor method and spectral analysis to the 24-hour profile of HS (orexigram) derived by a self-rating score (from 1 to 10 hunger units [HU]) recorded every half-hour. The study of circadian and ultradian recursivity on the orexigram was performed in 30 diabetic obese patients ([DOPs], 14 men and 16 women aged 22 to 62 years; body weight, 77 to 130 kg; body mass index, 31-47). The control group consisted of 30 clinically healthy subjects ([CHS], 15 men and 15 women aged 21 to 60 years; body weight, 65 to 72 kg; body mass index, 23 to 25). DOPs showed two types of orexigrams in which hunger was felt with limitation to the diurnal part of the day or with extension to the night, respectively. The type 1 orexigram was characterized by a normal spectrum and circadian rhythm. The type 2 orexigram was characterized by subsidiary ultradian components associated with an abnormal elevation of the circadian mesor and a significant delay of the circadian phase, as the spectral analysis was indicative of a structural difference in the frequencies that sustain the intraday and within-day recursivity of the HS. Accordingly, DOPs can be recognized by their orexigram as "eurectic" or "hyperrectic" to indicate subjects with a normal or an exaggerated HS, respectively, during the 24-hour span.

Chronobiometric identification of disorders of hunger sensation in essential obesity: therapeutic effects of dexfenfluramine.

In human beings, hunger is a proprioceptive signal that shows intraday (circadian components) and within-day (ultradian components) recursivity. Both periodic components can be investigated by chronobiometric procedures by combining the Cosinor method with spectral analysis. A 24-hour profile of hunger sensation (HS) can be plotted on a 1-to-10 scale of intensity using self-rated scores performed every half-hour of the day. Circadian and ultradian components were studied in 60 patients affected by essential obesity (20 men and 40 women; mean age, 38.4 years; mean body weight, 101 kg) before and after treatment with dexfenfluramine (Isomeride; Servier, Orléans, France) 15 mg orally twice daily, for 30 days. The control group consisted of 30 clinically healthy subjects (15 men and 15 women; mean age, 37.5 years; mean body weight, 69 kg). Chronobiometric analysis shows three patterns in obese patients, which suggests that HS may be normal (eurectic obesity), exaggerated (hyperrectic obesity), or diminished (hyporectic obesity). After dexfenfluramine administration, HS was showed a substantial decrease in the daily mean level. The spectrum of resolution in circadian and ultradian components was found to be maintained in eurectic obesity and partially readjusted in hyperrectic and hyporectic obesities. This demonstrates that dexfenfluramine acts not only as an anorectic but also as a chronizer by interfering with the recursive components of HS. The anorectic and chronizing effects suggest that dexfenfluramine is a "chronoanorectic drug" that interacts with the chronobiologic properties of the serotoninergic system.

Combination studies between polycationic peptides and clinically used antibiotics against Gram-positive and Gram-negative bacteria.

The in vitro interaction between five polycationic peptides, buforin II, cecropin P1, indolicidin, magainin II, and ranalexin, and several clinically used antimicrobial agents was evaluated against several clinical isolates of Gram-positive and Gram-negative aerobic bacteria, using the microbroth dilution method. The combination studies showed synergy between ranalexin and polymyxin E, doxycycline and clarithromycin. In addition, magainin II was shown to be synergic with betalactam antibiotics.

Evolution of neuropsychological changes after partial callosotomy in intractable epilepsy.

Early neuropsychological changes following partial anterior callosotomy were evaluated in 15 patients with epilepsy (10 secondary generalized and 5 Lennox-Gastaut syndromes) by comparing their performances 1 month before surgery and then 15-20 and 90-100 days postoperatively without modifying the anticonvulsant treatment. The following neuropsychological and motor functions were tested: memory, attention, visuo-motor ability, posture, motor dexterity, language, praxis and gnosis. Social behaviour was also investigated. The main results are as follows: (i) most cognitive functions showed no significant variation; (ii) motor organization was still slightly impaired at the second check-up after the surgery; (iii) improvements in social behaviour and posture were frequently observed at the final evaluation. The analysis of individual cases highlights the influence of the extent of commissurotomy, lesions related to the surgical procedure and preoperative brain damage in determining the post-surgical profile. On this basis, the short-term neuropsychological cost of partial callosotomy appears to be low and seems to depend mostly on surgical parameters and brain conditions before the operation.

Modifications in morphology of epileptic seizures after callosotomy.

The callosotomy on drug-resistant epileptic seizures may abolish or reduce their frequency and may modified the morphology of different kind of seizures. Our series is composed of 36 patients. Drop-attacks and complex partial seizures (CP) were present in all patients, generalized tonic-clonic seizures (GTC) in 16 (44.4%) and simple partial seizures (SP) and myoclonic attacks (MY) in 6 patients each. We found two kinds of modifications: a) lateralization of hypotonia which becomes hemisomatic, with lateral bending to the hypotonic side; b) different way of falling, due not only to the lateralization of hypotonia but also to the gradual impairment of muscle tone. Modifications in CP mainly concerned automatisms, which disappeared in 39.1% of patients, while 34.8% of them had a significant reduction in automatisms; this reduction consisted in simplification of automatic movements and in shorter duration of seizures.

Predictive factors of callosotomy in drug-resistant epileptic patients with a long follow-up.

Some possible factors to predict outcome after callosotomy were investigated in a personal series composed of 36 patients. Twenty-seven of them were submitted to anterior callosotomy, 1 to posterior callosotomy and the remaining 8 patients to two stage complete division of corpus callosum. All factors, either positive or negative, do not appear completely reliable; they can be envisaged only in relative terms and do not seem to be relevant to make surgical decision or to discard surgery. In author's series, dealing specifically with drop-attacks, it clearly appeared that abrupt falls to the ground unpreceded by other epileptic features did definitely better. This was the only statistically significant datum.

EEG Patterns after callosotomy.

In 36 patients with drug-resistant epilepsy submitted to anterior callosotomy (27 cases), to two-stage total callosotomy (8 cases) and to posterior callosotomy (1 case) the EEG variations concerning background activity, focal activity and sharp-waves (SW) bisynchronous activity were evaluated. EEG modifications observed after callosotomy are the following: background rhythm tends to be better organised as spectral analysis demonstrated, this finding usually coincide with reduction of bisynchronous discharges. It appears that improvement in background activity cannot be correlated with outcome, but it seems to be to some extent since at the same time cognitive functions also seem to improve; however, this last aspect need to be checked in much larger series. The number and location of EEG foci do not change, but they appear to be more active; this is likely to depend only on the concomitant reduction of bisynchronous activity. No correlation seems to exist between the number and the location of foci, which are generally multiple. Lateralization of bisynchronous discharges as well as the reduction of their frequency and duration were observed. However, the clinical course is quite different: in some patients we have achieved good clinical responses in others postoperative results were poor. Lateralization of bisynchronous discharges is never absolute, on the grounds that in prolonged recordings bisynchronous discharges are nearly always present. Bisynchronous discharges in some cases are alternatively predominant in both hemispheres even within minutes or seconds. It was observed that after certain time, generally some months, lateralized discharges tend to generalize again, confirming that corpus callosum is replaced in discharge diffusion by other structures (brain-stem, diencephalon).

Mutism in 36 patients who underwent callosotomy for drug-resistant epilepsy.

Thirty-six drug-resistant epileptic patients submitted to callosotomy were studied. Anterior callosotomy was performed in 27 patients, total two-stage callosotomy was performed in 8 patients and 1 patient had only posterior callosotomy. We found mutism in 10 patients (2 after complete callosotomy and 8 after anterior section). The patients did not speak, but the comprehension was present: they were able to carry out orders and to write. Their attitude to the environment was characterized by complete indifference. The mutism was always transient, lasting from 4 to 25 days (mean 7 days). Regression of mutism was always complete. We think that this complication should be chiefly attributed mainly to surgical manipulation, even if it is impossible to completely exclude a multi-factorial etiology.

Lipid anomaly in a child with partial duplication 3p.

The authors report a case regarding a 7-year-old girl affected by short height, bone growth delay, lipidic alterations (hypercholesterolemia, hypertriglyceridemia and high apolipoprotein B values) and by a partial duplication of the short arm of the third chromosome: 46,XX, dup(3)(p26-pter). This chromosomal alteration appears "de novo", as the parent's karyotypes are normal and none of the patient's next of kin showed evidence of lipidic anomalies. The patient's short height and slight frontal bossing were the only features that could be described as typical of the dup3p syndrome.

Methimazole treatment in Graves' disease: behaviour of CD5+B lymphocytes and regulatory T cell subsets.

In the present study we analyzed some circulating lymphocyte subsets in eleven patients affected by Graves' disease before and after three and six months of methimazole treatment. Peripheral blood mononuclear cells were studied by a panel of monoclonal antibodies with single and double fluorescence cytometric analysis. Our results demonstrated an increased percentage of CD5+B cells and HLADR+T lymphocytes at the beginning of the disease in comparison to the normal controls (p < 0.001), and a significant decrease after six months of treatment (p < 0.01 and p < 0.05, respectively). The CD4+ CD45RA+ subset was significantly reduced in untreated Graves' patients in comparison to the normal group (p < 0.01), and increased towards normalization after six months of treatment. The significant modifications of lymphocyte subsets, as well as the reduction of thyroid autoantibodies, support a direct or mediated effect of methimazole on the immune system.

[Congenital thyroid abnormality (subhyoid ectopy) associated with mitral valve prolapse]. / Anomalia congenita della tiroide (ectopia sottoioidea) associata a prolasso della mitrale.

By echocardiographic technique the Authors have studied a rare congenital anomaly: "sub-hyoid ectopy of the thyroid gland". The patient, a 35 years unmarried woman, with manifest clinic symptoms of hypothyroidism, was affected with mesotelesystolic prolapse of the posterior leaflet of the mitral valve. It has also been possible to put in evidence the findings of mixoedematous cardiopathy and its resolution after thyroid opotherapy.

[Atrial stunning and pharmacologic cardioversion in idiopathic atrial fibrillation of recent onset]. / Stunning atriale e cardioversione farmacologica di fibrillazione atriale idiopatica di recente insorgenza.

BACKGROUND: Normal atrial mechanic function may not return immediately after the successful cardioversion of atrial fibrillation. It has been suggested that the delayed recovery of atrial contraction (atrial stunning) might be due to: 1. the energy delivered during direct current cardioversion 2. the time from the onset of atrial fibrillation 3. the left atrial size 4. the associated cardiac disease. This study evaluates "atrial stunning" in patients pharmacologically treated, with atrial fibrillation of recent onset, normal atrial size and without heart disease. Doppler echocardiography is well suited for assessment of atrial function due to the ability of recording the peak velocity of atrial contraction (A wave). METHODS: Twenty-five patients with no evidence of heart disease and M-mode left atrial dimension less than 40 mm underwent successful pharmacologic cardioversion (pro-paphenon or flecainide 2 mg/kg/10 min) of atrial fibrillation of recent onset (less than 48 hours). After cardioversion an echocardiographic study was performed within 12 hours (ECO 1), on day 3 (ECO 2), on day 12 (ECO 3), and on day 30 (ECO 4). RESULTS: No significant difference of both left atrial size (37 +/- 3.9 mm; 38.22 +/- 3.8 mm; 38.02 +/- 4.7 mm; 38.2 +/- 4.14 mm) and peak E velocity (57.97 +/- 18.3 mm/sec; 59.4 +/- 18.3 mm/sec; 59.0 +/- 16 mm/sec; 59.07 +/- 16.7 mm/sec) was demonstrated among serial echocardiographic evaluations. Both peak A velocity (mm/sec) and E/A ratio were significantly different in ECO 1 (60.29 +/- 12.3-1.0 +/- 0.37) than in ECO 2 (73.1 +/- 10.7, p < 0.005-0.82 +/- 0.27, p < 0.05); no statistical difference was found between ECO 2 and ECO 3 (76.31 +/- 12-0.78 +/- 0.24 mm/sec)--ECO 4 (76.91 +/- 14.8-0.78 +/- 0.21 mm/sec). CONCLUSIONS: This study suggests that patients with atrial fibrillation of recent onset have a delayed recovery of normal atrial systolic function after pharmacologic cardioversion.

[Endemic goiter in Latium: environmental and genetic factors]. / Gozzo endemico nel Lazio: fattori ambientali e fattori genetici.

Most studies on the pathogenesis of endemic goiter focus above all on iodine deficiency. In some endemic goiter areas (i.e. Nigeria) there is no evidence of iodine deficiency; therefore, we suggest the taking into account of various factors, both environmental and non-environmental. We report the results of two studies carried out in three different areas in Latium: one of them (Cerveteri, RM) could be classified as high prevalence of goiter area, while the two others (Roccasecca dei Volsci, LT and Castel San Pietro Romano, RM) are true endemic goiter areas. The role of environmental factors, radioactivity and electromagnetism, foodstuff, the hydrogeological and chemical composition of natural water and the importance of genetics are here discussed, assuming that the endemic goiter could have a multifactorial pathogenesis.

[Remarks on callosotomy in the treatment of drug-resistant epilepsy]. / Remarques sur la callosotomie dans le traitement de l'épilepsie pharmaco-résistante.

In this report 17 patients with long-standing non-focal epilepsy underwent callosotomy (this was total in two patients and performed in two stages, and anterior-subtotal in the remaining patients). In all patients the atonic-hypertonic seizures with sudden falls were the most disabling epileptic fits. Callosotomy proved efficient in controlling atonic fits in 10 out of 15 patients in whom surgical results are evaluated. In 3 additional patients the frequency of atonic fits was reduced by more than 50%. In the remaining two patients, no therapeutic effect was observed. Callosotomy was less effective on seizures which were not atonic. Therefore, this procedure appears to be indicated in patients in whom atonic fits are predominant. The main effect of callosotomy is to transform drug-resistant seizures into drug-sensitive ones. Neuropsychological sequels are insignificant unless the splenium is severed. However, considerable psychic and behavioral improvement was nearly always observed after surgery. Despite the fact that on a therapeutic level results were often satisfactory, a number of practical problems still remain. These concern the full spectrum of indications for callosotomy, the extent of corpus callosum section, choice of methods in severely mentally retarded patients and, finally, the age at which the operation should be carried out.