Characterizing renal involvement in Hermansky-Pudlak Syndrome in a zebrafish model.

Hermansky-Pudlak Syndrome (HPS) is a rare disease caused by mutations in the genes coding for various HPS proteins. HPS proteins are part of multi-subunit complexes involved in the biogenesis of organelles from the lysosomal-endosomal-system. In humans, this syndrome is characterized by the presence of albinism, platelet dysfunction and pulmonary fibrosis. The renal component to the disease remains unstudied and untreated in patients with HPS. Here we demonstrate that in humans, HPS proteins have a high renal expression with active transcription of HPS1, 3, 4 and 5 in human podocyte cell culture, suggesting that impaired function of HPS proteins could directly impact renal function. Therefore, we developed a zebrafish model to study the renal involvement of HPS proteins in proteinuric kidney disease. Remarkably, knockdown of HPS genes in zebrafish causes glomerular injury with edema, proteinuria and structural changes of the glomerular filtration barrier. Moreover, reduced expression of HPS proteins in zebrafish recapitulates other important disease hallmarks, like hypopigmentation and accumulation of intracellular debris characteristic of lysosomal disorders. In conclusion, we present a valid zebrafish model that highlights the previously underestimated relevance of renal disease in HPS. This draws attention to the therapeutic options available to manage this component of the syndrome.

Circulating factors cause proteinuria in parabiotic zebrafish.

Proteinuria can be induced by impairment of any component of the glomerular filtration barrier (GFB). To determine the role of circulating permeability factors on glomerular damage, we developed a parabiosis-based zebrafish model to generate a common circulation between zebrafish larvae. A morpholino-mediated knockdown of a podocyte specific gene (nephronectin) was induced in one zebrafish larva which was then fused to an un-manipulated fish. Notably, proteinuria and glomerular damage were present in the manipulated fish and in the parabiotically-fused partner. Thus, circulating permeability factors may be induced by proteinuria even when an induced podocyte gene dysregulation is the initiating cause.

What do parents want for their children who are overweight when visiting the paediatrician?

OBJECTIVE: The objective of this study was to determine whether parental preferences regarding primary care weight-management strategies differ by child age, gender, overweight severity, race/ethnicity or parental agreement that their child is overweight. METHODS: A survey was administered to parents of 2- to 18-year-old children who are overweight at an academic primary-care clinic regarding perception of child overweight, helpful/harmfulness of having the child present during weight discussions, and dietary-advice preferences. Multivariable analyses examined factors associated with preferred weight-management strategies, after adjustment for parent/child characteristics. RESULTS: Eighty-three per cent of parents agreed that a child's presence during weight discussions is helpful/very helpful, 74% that paediatricians should prescribe specific diets, and 55% preferred specific vs. general dietary advice only (N = 219). In multivariable analyses, characteristics associated with helpfulness of child presence included older child age (vs. 2-5 year olds, 6-11 year olds: odds ratio [OR], 4.6; 95% CI, 1.3-16; 12- to 18-year-olds: OR, 23; 95% CI, 4-136), male gender (OR, 5.0; 95% CI, 1.7-10) and obesity (vs. overweight: OR, 2.8; 95% CI, 1.7-12). Characteristics associated with preferring specific diets included Latino race/ethnicity (OR, 5.3; 95% CI, 3-12), older age (vs. 2-5 year olds, 6-11 year olds: OR, 2.8; 95% CI, 1.1-7; 12-18 year olds: OR, 3.7; 95% CI, 1.5-10) and agreement that the child is overweight (OR, 2.3; 95% CI, 1.1-5) and, for specific dietary advice, older age (vs. 2-5 year olds: OR, 2.3; 95% CI, 1.1-5) and agreement that the child is overweight (OR, 2.1; 95% CI, 1.2-4). CONCLUSIONS: Findings suggest that weight-management strategies tailored to child age, gender, over-weight severity, race/ethnicity and parental agreement that their child is overweight may prove useful in improving child weight status.

Nuclear localization of cystatin B, the cathepsin inhibitor implicated in myoclonus epilepsy (EPM1).

Cystatin B is an anti-protease implicated in myoclonus epilepsy, a degenerative disease of the central nervous system. In vitro, cystatin B interacts with and inhibits proteases of the cathepsin family. Confocal microscopy analysis of the subcellular localization of cystatin B and cathepsin B shows that, in vivo, the two proteins are concentrated in different cell compartments. In fact, cystatin B is found mainly in the nucleus of proliferating cells and both in the nucleus and in the cytoplasm of differentiated cells, while cathepsin B, in either case, is essentially cytoplasmic. However, colocalization of cystatin and cathepsin B is observed in the isolated cell matrix and in the nuclear scaffold of differentiated neuroblastoma cells but not of proliferating cells. This suggests that at least a fraction of cystatin B is bound to the protease in differentiated cells. The electron microscopy analysis of the cell matrix confirms the observation made with confocal microscopy. The cellular activity of cathepsin B was analyzed with a fluorogenic cytochemical assay. A fluorescent signal is observed in the cytoplasm of proliferating cells but is undetectable in the cytoplasm of differentiated cells, suggesting that cathepsin B is active mainly during the cell cycle. This result is consistent with the separate compartimentalization of cystatin B and cathepsin B that we have observed in growing cells.

Responding to threat: hemispheric asymmetries and interhemispheric division of input.

This investigation examined how hemispheric asymmetry and interhemispheric processing contribute to attentional biases toward emotional information. Participants (n = 88) named the color of lateralized squares presented concurrently with neutral, positive, or threatening words. A left-hemisphere advantage in color naming was reduced when distractors were emotional, suggesting right-hemisphere priming by emotional stimuli. Furthermore, the advantage of dividing the word and color across visual fields was increased for emotion words when they were frequently presented, indicating a strategic use of interhemispheric division of labor to reduce the distracting effect of emotional words. Finally, participants with high levels of anxious apprehension were most likely to make use of this interhemispheric processing strategy, supporting a processing efficiency theory of cognitive function in anxiety.

Contrasting patterns of brain activity in anxious apprehension and anxious arousal.

Evidence suggests that a distinction between anxious apprehension (worry) and anxious arousal (somatic anxiety) might account for some discrepancies in the literature examining brain activity in anxiety. In the current study, we compared the regional brain activity of groups of anxious apprehension and anxious arousal participants, selected on the basis of self-report measures previously shown to be psychometrically distinct from each other and from a specific measure of depression. Patterns of hemispheric asymmetry in electroencephalogram alpha distinguished the two types of anxiety, with the anxious arousal group showing more right than left activity. No significant asymmetry was found for the anxious apprehension group. The results provide further support for contrasting patterns of brain activity in distinct types of anxiety. Research is needed to specify further the topography and functional significance of this distinction.

[Multilocular cystic nephroma in children. Description of a case]. / Nefroma cistico multiloculare in età pediatrica. Descrizione di un caso.

In paediatric age there may occur the various types of cystic renal tumor also of different clinical meaning; we can count among them shapes openly or potentially deadly, among which Wilms tumor cystic owing to haemorrhages and tumoral necrosis, congenital mesoblastic cystic nephroma, clear cell carcinoma, cystic, partially differentiated nephroblastoma (CPDN) and benign forms such as multilocular cystic nephroma (MLCN), cystic localized dysplasia of the kidney. In some cases, the differential diagnosis is difficult and it becomes only by histology: particularly the differential diagnosis between MLCN and CPDN, indistinguishable on the basis of the imaging and the macroscopic aspect, it is possible only by histology. It is described a case of multicystic lesion in a baby, male, aged twenty-two months, with an indolent mass of left side, screened by US and TC. The US examination has put into evidence the presence of renal with clean outlines of eight cms, formed by multiple small cysts, divided by thin regular septa . These aspects have been confirmed by TC. The histological examination has diagnosed a multilocular cystic nephroma, without atypias. Therefore, the multilocular cystic lesions of the kidney have to be considered potentially malignant and submitted to surgical treatment.

[Food allergy in children. Diagnostic difficulties, doubts and digressions]. / Allergia alimentare nel bambino. Difficoltà diagnostiche, dubbi, divagazioni.

It is very difficult to diagnose an alimentary allergy especially because of: the difference among individuals in their physical, psychic and humoral reactions to the environment; weakness and variability of these reactions during the puberty; limited reliability in the results of certain kind of research (i.e. false positiveness and negativeness, discordance between laboratory results and the results of the challenge, neutralization of diagnostic antigenic extracts and/or the presence in these extracts of lectin, etc.); the bad compliance of some therapies and their restricted efficaciousness, particularly in the little children. Moreover: the superimposition of the clinical manifestations of alimentary allergy and pseudoallergy with those of allergy, the possibility of an association between the alimentary and the respiratory allergy, the acquisition on behalf of the allergic child of other kinds of allergy, false polyallergy, the allergy might change its seats and in consequence also its manifestations. The authors, apart a short account of the different diagnostic methods, lay stress on the challenge as the most reliable. They discuss upon the dose of a nourishment that can be given to the patient without risk, besides they suggest to take into account the type and the seriousness of the clinical manifestations in fixing this dose.

Efficacy and tolerance of acetate free biofiltration: a central Italian multicenter trial.

One hundred and thirteen patients from 51 dialysis units have been treated for 12 months on AFB using a high flux AN69 dialyzer (Filtral 12 or 16-Hospal), a buffer free dialysate (Na+ 139, K+ 2, Ca++ 2 mmol/liter, glucose 1 g/liter) and a reinfusate solution containing 145 mmol/liter HCO3Na. All of them had previously been stabilized on acetate dialysis (30 patients) or bicarbonate dialysis (46 patients) or different dialysis procedures (37 patients). AFB sessions were performed for 3.71 +/- 0.28 hrs, three times a week, at an average blood flow of 308 +/- 8.5 ml/min so as to ensure a stable Kt/V value > 1 (1.16 +/- 0.08). Blood samples were drawn monthly pre- and post-dialysis, for blood electrolytes, calcium, phosphate, chloride, urea, creatinine and uric acid, proteins and lipid profiles, hemochrome. Body weights, blood pressures and adverse side effects were recorded at each session. Using a mean infusion volume of 7.96 +/- 0.61 liter/session, post-dialytic bicarbonate values consistently > 25 mmol/liter (26.33 +/- 2.71) were achieved. Intradialytic occurrence of symptoms was very low at an average rate < 1.5 episodes patient/month. After 12 months of Tx an adequate control of uremia, of electrolytes, of Ca-PO4 balance and of BP was obtained. AFB gets a very high intradialytic tolerance and an excellent depurative capacity which contributes to the well being of the patients.

Lipids in the progression of chronic renal failure.

Lipid disturbances have been linked to the progression of chronic renal disease. We examined 52 patients with a creatinine clearance (CCr) of 38.5 +/- 7.9 ml/min due to various nephropathies, on free diet. Bimonthly, over a 12-month period, we assessed: serum creatinine (Cr); CCr; daily urinary urea excretion; urinary protein excretion per unit of residual renal function (UProt/CCr); total, HDL, VLDL and LDL cholesterol; triglycerides; Apo A, Apo B. Chronic renal failure was progressive in 22 patients with a slope of 1/Cr-0.00358 +/- 0.00247, stable in 30 with a slope of 0.00420 +/- 0.00285. Lipid parameters did not differ significantly between the two groups but for the lower Apo A and Apo A/Apo B ratio values in the progressive group. Overall slope inversely correlated with basal CCr; in the progressive patients the slope correlated with the percentage variation of UProt/CCr and only partially with the altered Apo profile.

Zinc-mediated lymphocyte energy charge modification in dialysis patients.

The authors studied the effects of 6 months of zinc therapy on cell-mediated immunity in regular dialysis therapy patients. Serum zinc was significantly enhanced (p less than 0.01) at 2 months. While cells, OKT3, and OKT4 did not show significant variation, but after 6 months of therapy a significant (p less than 0.02) decrease of OKT8 cells, with enhancement of the OKT4/OKT8 ratio, and a significant (p less than 0.01) increase in the Multitest Composite score were found. At the same time, a significant elevation (p less than 0.001) of adenosine triphosphate (ATP), and a reduction (p less than 0.01) of lymphocyte adenosine monophosphate was seen; consequently, energy charge levels increased. Zinc-induced improvement of uremic lymphocyte function is likely mediated by an increase in intracellular ATP.

[IgA deficiency in pediatrics]. / Deficit di IgA in pediatria.

To evaluate the IgA deficiency we have considered 368 children, admitted to "Day hospital" for different pathologies: 64 of them had serum IgA levels lower than the normal values for their age according to Ellis and Robbin. The age of the children with this deficiency was included from 4 months up to 8 years: 39 were boys, 25 were girls. In 54 cases the IgA deficiency was "partial" that is: the IgA value found out was lower than the normal for the age, but higher than 5 mg%. In 10 cases the IgA deficiency was "severe" (the IgA value was lower than 5 mg%). Six cases, among the 29 ones with intestinal diseases, had a severe deficiency, whereas among the 22 cases with respiratory diseases 3 had a "severe" deficiency. The 2 patients with urinary disease had a partial deficiency; only one case of the remaining 11 with different pathologies had a "severe" deficiency. Among the carriers of serum IgA deficiency an high incidence of chronic pathology has been found out (83%). Nevertheless the percentage of IgA deficiency extrapolated from the all case histories doesn't differ very much (64 cases among 368 = 17.39%) considering only those patients with chronic relapsing pathology (53 cases among 275 = 18.2%). Therefore it seems that the IgA deficiency could be considered a chronicizing factor in the examinated pathology even if in few cases. Anyway the frequency of IgA deficiency has reached major values (29/54; 45.3%) in the patients with enteric diseases. The frequency of IgA deficiency is smaller but still important in those patients with respiratory diseases (22/64: 34.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

[Short near-fainting in children with or without loss of conscience]. / Malesseri fugaci del bambino con o senza perdita di coscienza.

Short near-faints with or without loss of consciousness have different etiologies and pathogenesis and, according to these, they recur with various frequency. This subject was reported on several publications and here is again examined with the contribute of personal experience and the description of distinct cases. The following causes were examined: vagal hypertonia, digestive troubles (gastroesophageal reflux), metabolic troubles (cyclic ketosis, hypoglycemia and hypocalcemia with peculiar clinic manifestations). Among the neurological causes were examined: epilepsy, benign paroxysmal vertigos and, particularly, the so called breath-holding spells and the migraine, about that were reported a few examples of "migraine accompagnée". Among the cardiovascular causes (ischaemic cerebral crisis), -particular attention was dedicated to orthostatic hypotension syncope. A short hint about hysteria ends the exposition of psychical causes of short near-faints.

Computerised non-invasive monitoring of cardiovascular stress in haemodialysis patients.

Haemodynamic instability is one of the most frequent problems occurring during dialysis treatment. Ten clinically stable patients (8 M and 2 F) undergoing chronic maintenance haemodialysis for at least 6 months were investigated. Two groups of five patients each, were selected on the basis of presence (IG) or absence (SG) of cardiovascular instability during dialysis. The cardiovascular function was assessed by computerised electrical bioimpedance performed during dialysis setting and by echocardiography immediately pre- and post-dialysis. In SG dialysis treatment did not change cardiac index (CI), stroke index (SI) and systemic vascular resistances index (SVRI). However CI, SI and SVRI, tended to decrease in IG patients; the reduction in CI was primarily due to a decrease in SI. Ejection velocity index increased significantly in SG but not in IG. Evaluation of cardiac function by Döppler echocardiography revealed a significant increment in fractional shortening, mean velocity of circumferential fiber shortening and Suga' index in SG with dialysis but not in IG. Stress index decreased significantly in both groups. Hormonal and biochemical parameters were not significantly different before and after dialysis in both groups. In IG the decrease in mean blood pressure, due to a reduction of SI, recognises in the inadequate response of myocardial contractility to volume subtraction, the genesis of its drop. Finally, impedance cardiography in uraemic patients helps to identify the factors that contribute to the impairment of cardiac performance and that should be studied before selecting new and advanced dialysis programmes.

Electrophysiological aspects of nervous conduction in uremia.

Some neurophysiological techniques have been employed in clinical nephrology to record abnormalities of nervous conduction in central and peripheral pathways. The electrical monitoring on the peripheral and central nervous systems has allowed the detection of uremic neural injury, the diagnosis of specific electrophysiological abnormalities, the evaluation of various treatments employed and the identification of those abnormalities that uremia can induce. A group of 156 subjects subdivided into four groups were examined: 100 healthy subjects (64 M, 36 F); 56 patients (21 glomerulonephritis, 14 pyelonephritis, 5 nephrolithiasis, 5 polycystic kidney, 4 nephroangiosclerosis, 7 undetermined) with chronic renal failure treated with a conventional low nitrogen diet (CLND, 0.6 g/kg b.w./d. of proteins), 8 of whom passed from CLND to a very low nitrogen diet supplemented with alpha-keto-analogues; a group of 22 of these 56 underwent a regular dialysis treatment for 12 to 15 hours/weekly for 40.5 +/- 10.2 months. Three patients of the CLND group and 13 patients underwent renal transplantation after a variable period of RDT. In the uremic patients we found different populations of motor unit potentials; a decreased MNCV was found in 35% of the CLND patients, RDT patients had slowed MNCV in 42%. The SNCV was compromised more frequently than the MNCV. An increased duration of evoked potentials was sometimes observed in CLND and RDT patients inducing us to consider this a hallmark of uremic syndrome. The alpha-keto-analogues and HD/HP treated patients showed an improvement in several features.(ABSTRACT TRUNCATED AT 250 WORDS)