Retraction Note: Autoantibodies detection in patients affected by autoimmune retinopathies.

The article "Autoantibodies detection in patients affected by autoimmune retinopathies", by M.R. Ceccarini, M.C. Medori, K. Dhuli, S. Tezzele, G. Bonetti, C. Micheletti, P.E. Maltese, S. Cecchin, K. Donato, L. Colombo, L. Rossetti, G. Staurenghi, A.P. Salvetti, M. Oldani, L. Ziccardi, D. Marangoni, G. Iarossi, B. Falsini, G. Placidi, F. D'Esposito, F. Viola, M. Nassisi, G. Leone, L. Cimino, L. De Simone, V. Mastrofilippo, T. Beccari, M. Bertelli, published in Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 57-63-DOI: 10.26355/eurrev_202312_34690-PMID: 38112948 has been retracted by the Editor in Chief for the following reasons. Following some concerns raised on PubPeer, the Editor in Chief has started an investigation to assess the validity of the results. The outcome of the investigation revealed that the manuscript presented major flaws in the following: -       Issues with ethical approval -       Undeclared conflict of interest In light of concerns regarding the potential manipulation of Supplementary Figure 2, the journal's inquiry has been unable to conclusively determine whether the alterations noted on PubPeer constitute figure manipulation. The investigation yielded divergent evaluations. However, given the aforementioned concerns, the Editor in Chief doubts the integrity of the findings presented and thus, has opted to retract the article. The authors disagree with this retraction. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34690.

Autoantibodies detection in patients affected by autoimmune retinopathies.

OBJECTIVE: Autoimmune retinopathies (ARs) encompass a spectrum of immune diseases that are characterized by the presence of autoantibodies against retinal proteins in the bloodstream. These autoantibodies (AAbs) lead to a progressive and sometimes rapid loss of vision. ARs commonly affect subjects over 50 years of age, but also rare cases of kids under 3 years of age have been reported. PATIENTS AND METHODS: In this study, 47 unrelated Caucasian patients were enrolled. All subjects showed negative cancer diagnoses and negative results in their genetic screenings. We studied 8 confirmed retinal antigens using Western blotting analysis, with α-enolase followed by carbonic anhydrase II being the two most frequently found in the patients' sera. RESULTS: Nineteen patients were positive (40.4%), thirteen uncertain (27.7%), and fifteen were negative (31.9%). Their gender did not correlate with the presence of AAbs (p=0.409). CONCLUSIONS: AAbs are responsible for retinal degeneration in some cases, while in others, they contribute to exacerbating the progression of the disease; however, their detection is crucial to reaching a better diagnosis and developing more effective treatments for these conditions. Moreover, finding good biomarkers is important not only for AR monitoring and prognosis, but also for helping with early cancer diagnosis.

Capsid Engineering Overcomes Barriers Toward Adeno-Associated Virus Vector-Mediated Transduction of Endothelial Cells.

Endothelial cells (EC) are targets in gene therapy and regenerative medicine, but they are inefficiently transduced with adeno-associated virus (AAV) vectors of various serotypes. To identify barriers hampering efficient transduction and to develop an optimized AAV variant for EC transduction, we screened an AAV serotype 2-based peptide display library on primary human macrovascular EC. Using a new high-throughput selection and monitoring protocol, we identified a capsid variant, AAV-VEC, which outperformed the parental serotype as well as first-generation targeting vectors in EC transduction. AAV vector uptake was improved, resulting in significantly higher transgene expression levels from single-stranded vector genomes detectable within a few hours post-transduction. Notably, AAV-VEC transduced not only proliferating EC but also quiescent EC, although higher particle-per-cell ratios had to be applied. Also, induced pluripotent stem cell-derived endothelial progenitor cells, a novel tool in regenerative medicine and gene therapy, were highly susceptible toward AAV-VEC transduction. Thus, overcoming barriers by capsid engineering significantly expands the AAV tool kit for a wide range of applications targeting EC.

Misdiagnosis of X-linked retinitis pigmentosa in a choroideremia patient with heavily pigmented fundi.

Inherited retinal diseases are thought to be the leading cause of sight loss in the working age population. Mutations found in the RPGR and CHM genes cause retinitis pigmentosa (RP) and choroideremia, respectively. In the first instance, an X-linked family history of visual field loss commonly raises the suspicion of one of these two genes. In choroideremia, the classic description of a white fundal reflex secondary to the widespread chorioretinal degeneration was made over a hundred years ago in Caucasians. But, it is not so obvious in heavily pigmented fundi. Hence, the clinical diagnosis of CHM in non-Caucasian patients may be challenging in the first stages of the disease. Here we report a case of a Southeast Asian gentleman who has a family history of X-linked retinal degeneration and was found to have a confirmed in-frame deletion of 12 DNA nucleotides in exon 15 of the RPGR gene. Later in life, however, his fundal appearance showed unusual areas of circular pigment hypertrophy and clumping. He was therefore tested for carrying a disease-causing mutation in the CHM gene and a null mutation was found. Since gene therapy trials are ongoing for both of these conditions, it has now become critically important to establish the correct genetic diagnosis in order to recruit suitable candidates. Moreover, this case demonstrates the necessity to remain vigilant in the interpretation of genetic results which are inconsistent with clinical features.

Host and symbiont intraspecific variability: The case of Paramecium calkinsi and "Candidatus Trichorickettsia mobilis".

Newly isolated strains of the ciliate Paramecium calkinsi and their cytoplasmic bacterial endosymbionts were characterized by a multidisciplinary approach, including live observation, ultrastructural investigation, and molecular analysis. Despite morphological resemblance, the characterized P. calkinsi strains showed a significant molecular divergence compared to conspecifics, possibly hinting for a cryptic speciation. The endosymbionts were clearly found to be affiliated to the species "Candidatus Trichorickettsia mobilis" (Rickettsiales, Rickettsiaceae), currently encompassing only bacteria retrieved in an obligate intracellular association with other ciliates. However, a relatively high degree of intraspecific divergence was observed as well, thus it was possible to split "Candidatus Trichorickettsia" into three subspecies, one of which represented so far only by the newly characterized endosymbionts of P. calkinsi. Other features distinguished the members of each different subspecies. In particular, the endosymbionts of P. calkinsi resided in the cytoplasm and possessed numerous peritrichous flagella, although no motility was evidenced, whereas their conspecifics in other hosts were either cytoplasmic and devoid of flagella, or macronuclear, displaying flagellar-driven motility. Moreover, contrarily to previously analyzed "Candidatus Trichorickettsia" hosts, infected P. calkinsi cells frequently became amicronucleate and demonstrated abnormal cell division, eventually leading to decline of the laboratory culture.

Technique of retinal gene therapy: delivery of viral vector into the subretinal space.

PurposeSafe and reproducible delivery of gene therapy vector into the subretinal space is essential for successful targeting of the retinal pigment epithelium (RPE) and photoreceptors. The success of surgery is critical for the clinical efficacy of retinal gene therapy. Iatrogenic detachment of the degenerate (often adherent) retina in patients with hereditary retinal degenerations and small volume (eg, 0.1 ml) subretinal injections pose new surgical challenges.MethodsOur subretinal gene therapy technique involved pre-operative planning with optical coherence tomography (OCT) and autofluorescence (AF) imaging, 23 G pars plana vitrectomy, internal limiting membrane staining with Membrane Blue Dual (DORC BV, Zuidland, Netherlands), a two-step subretinal injection using a 41 G Teflon tipped cannula (DORC) first with normal saline to create a parafoveal bleb followed by slow infusion of viral vector via the same self-sealing retinotomy. Surgical precision was further enhanced by intraoperative OCT (Zeiss Rescan 7000, Carl Zeiss Meditec AG, Jena, Germany). Foveal functional and structural recovery was evaluated using best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, microperimetry and OCT.ResultsTwo patients with choroideremia aged 29 (P1) and 27 (P2) years, who had normal and symmetrical levels of best-corrected visual acuity (BCVA) in both eyes, underwent unilateral gene therapy with the fellow eye acting as internal control. The surgeries were uncomplicated in both cases with successful detachment of the macula by subretinal vector injection. Both treated eyes showed recovery of BCVA (P1: 76-77 letters; P2: 84-88 letters) and mean threshold sensitivity of the central macula (P1: 10.7-10.7 dB; P2: 14.2-14.1 dB) to baseline within a month. This was accompanied by normalisation of central retinal thickness on OCT.ConclusionsHerein we describe a reliable technique for subretinal gene therapy, which is currently used in clinical trials to treat choroideremia using an adeno-associated viral (AAV) vector encoding the CHM gene. Strategies to minimise potential complications, such as avoidance of excessive retinal stretch, air bubbles within the injection system, reflux of viral vector and post-operative vitritis are discussed.

Psorisis Infantil: Prevalencia y formas clínicas. Nuestra experiencia en un hospital pediátrico público / Chilhood Psoriasis: Prevalence and clinical types. Our experence in a pediatric publical hospital

El principal objetivo de este trabajo es conocer la prevalencia de la psoriasis en menores de 16 años inclusive, en relación al total de las consultas por dicha patología, en el servicio de dermatología del hospital Pediátrico del Niño Jesús, en el período comprendido entre Julio de 2008 y Agosto de 2009. Durante este período se atendieron 5753 consultas dermatológicas, entre niños y adultos, ya que en dicho servicio se atienden todos los grupos etarios. De 5753 consultas dermatológicas, 115 pacientes correspondieron a psoriasis, de los cuales 26 eran menores de 17 años. Se estudiaron retrospectivamente 26 niños entre los 3 meses y 16 años. Siendo las mujeres las más afectadas con una relación mujer-hombre de 4,2:1. El grupo etario más afectado fue entre los 9 y 13 años. Los factores desencadenantes, tanto externos como sistémicos, pueden inducir la psoriasis en individuos predispuestos genéticamente. En nuestro trabajo las infecciones se observaron en 8 pacientes (30,77%), el estrés psicógeno y los fármacos fueron observados en 2 casos cada uno (7,7%). La forma clínica mas observada fue la vulgar o en placas en 12 pacientes (46,15%) y la "guttata", siendo el prurito el síntoma más común en 18 (69,23%). El 88,46% de los casos fueron tratados exitosamente con terapéuticas tópicas y solo el 11,54%, requirió tratamientos sistémicos específicos para la entidad Se concluye que la prevalencia en relación al total de las consultas de psoriasis, en este lapso y en este hospital, fue del 22,6% para este grupo etario.

The main objective of this study was to determine the prevalence of psoriasis in children less than 16 years including in relation to the total number of consultations for this disease in the dermatology service at Pediatric Hospital "Niño Jesus", since July 2008 to August 2009. During this period of time 5753 dermatological consultations were attended, children and adults as well. In 5753 dermatological consultations, 115 were for psoriasis patients, of whom 26 were under 17. We studied 26 children between 3 months and 16 years. Women being the most affected with a female man 4,2: 1. The most affected age group was between 9 and 13. The precipitating factors, both external and systemic, may raise psoriasis in predisposed individuals from the genetic standpoint, in this study infections were observed in 8 patients (30.77%), psychogenic stress in 2 of them (7, 7%), and drugs also in 2 (7.7%) The clinical variant most common were the vulgar-plaques and guttate in 12 patients (46.15%) and pruritus the most common symptom in 18 (69.23%). The 88.46% of the cases were successfully treated with topical treatment and only 11.54% required more aggressive treatment. We conclude that this age group is frequently affected by psoriasis with prevalence in relation with total visits for the pathology of 22.6%. In the future, it will be interesting to investigate more deeply childhood psoriasis in our city due it important prevalence and to correlate the findings with other local or international studies.

Psorisis Infantil: Prevalencia y formas clínicas. Nuestra experiencia en un hospital pediátrico público / Chilhood Psoriasis: Prevalence and clinical types. Our experence in a pediatric publical hospital

El principal objetivo de este trabajo es conocer la prevalencia de la psoriasis en menores de 16 años inclusive, en relación al total de las consultas por dicha patología, en el servicio de dermatología del hospital Pediátrico del Niño Jesús, en el período comprendido entre Julio de 2008 y Agosto de 2009. Durante este período se atendieron 5753 consultas dermatológicas, entre niños y adultos, ya que en dicho servicio se atienden todos los grupos etarios. De 5753 consultas dermatológicas, 115 pacientes correspondieron a psoriasis, de los cuales 26 eran menores de 17 años. Se estudiaron retrospectivamente 26 niños entre los 3 meses y 16 años. Siendo las mujeres las más afectadas con una relación mujer-hombre de 4,2:1. El grupo etario más afectado fue entre los 9 y 13 años. Los factores desencadenantes, tanto externos como sistémicos, pueden inducir la psoriasis en individuos predispuestos genéticamente. En nuestro trabajo las infecciones se observaron en 8 pacientes (30,77%), el estrés psicógeno y los fármacos fueron observados en 2 casos cada uno (7,7%). La forma clínica mas observada fue la vulgar o en placas en 12 pacientes (46,15%) y la "guttata", siendo el prurito el síntoma más común en 18 (69,23%). El 88,46% de los casos fueron tratados exitosamente con terapéuticas tópicas y solo el 11,54%, requirió tratamientos sistémicos específicos para la entidad Se concluye que la prevalencia en relación al total de las consultas de psoriasis, en este lapso y en este hospital, fue del 22,6% para este grupo etario.(AU)

The main objective of this study was to determine the prevalence of psoriasis in children less than 16 years including in relation to the total number of consultations for this disease in the dermatology service at Pediatric Hospital "Niño Jesus", since July 2008 to August 2009. During this period of time 5753 dermatological consultations were attended, children and adults as well. In 5753 dermatological consultations, 115 were for psoriasis patients, of whom 26 were under 17. We studied 26 children between 3 months and 16 years. Women being the most affected with a female man 4,2: 1. The most affected age group was between 9 and 13. The precipitating factors, both external and systemic, may raise psoriasis in predisposed individuals from the genetic standpoint, in this study infections were observed in 8 patients (30.77%), psychogenic stress in 2 of them (7, 7%), and drugs also in 2 (7.7%) The clinical variant most common were the vulgar-plaques and guttate in 12 patients (46.15%) and pruritus the most common symptom in 18 (69.23%). The 88.46% of the cases were successfully treated with topical treatment and only 11.54% required more aggressive treatment. We conclude that this age group is frequently affected by psoriasis with prevalence in relation with total visits for the pathology of 22.6%. In the future, it will be interesting to investigate more deeply childhood psoriasis in our city due it important prevalence and to correlate the findings with other local or international studies.(AU)

Psorisis Infantil: Prevalencia y formas clínicas. Nuestra experiencia en un hospital pediátrico público / Chilhood Psoriasis: Prevalence and clinical types. Our experence in a pediatric publical hospital

El principal objetivo de este trabajo es conocer la prevalencia de la psoriasis en menores de 16 años inclusive, en relación al total de las consultas por dicha patología, en el servicio de dermatología del hospital Pediátrico del Niño Jesús, en el período comprendido entre Julio de 2008 y Agosto de 2009. Durante este período se atendieron 5753 consultas dermatológicas, entre niños y adultos, ya que en dicho servicio se atienden todos los grupos etarios. De 5753 consultas dermatológicas, 115 pacientes correspondieron a psoriasis, de los cuales 26 eran menores de 17 años. Se estudiaron retrospectivamente 26 niños entre los 3 meses y 16 años. Siendo las mujeres las más afectadas con una relación mujer-hombre de 4,2:1. El grupo etario más afectado fue entre los 9 y 13 años. Los factores desencadenantes, tanto externos como sistémicos, pueden inducir la psoriasis en individuos predispuestos genéticamente. En nuestro trabajo las infecciones se observaron en 8 pacientes (30,77%), el estrés psicógeno y los fármacos fueron observados en 2 casos cada uno (7,7%). La forma clínica mas observada fue la vulgar o en placas en 12 pacientes (46,15%) y la "guttata", siendo el prurito el síntoma más común en 18 (69,23%). El 88,46% de los casos fueron tratados exitosamente con terapéuticas tópicas y solo el 11,54%, requirió tratamientos sistémicos específicos para la entidad Se concluye que la prevalencia en relación al total de las consultas de psoriasis, en este lapso y en este hospital, fue del 22,6% para este grupo etario.(AU)

The main objective of this study was to determine the prevalence of psoriasis in children less than 16 years including in relation to the total number of consultations for this disease in the dermatology service at Pediatric Hospital "Niño Jesus", since July 2008 to August 2009. During this period of time 5753 dermatological consultations were attended, children and adults as well. In 5753 dermatological consultations, 115 were for psoriasis patients, of whom 26 were under 17. We studied 26 children between 3 months and 16 years. Women being the most affected with a female man 4,2: 1. The most affected age group was between 9 and 13. The precipitating factors, both external and systemic, may raise psoriasis in predisposed individuals from the genetic standpoint, in this study infections were observed in 8 patients (30.77%), psychogenic stress in 2 of them (7, 7%), and drugs also in 2 (7.7%) The clinical variant most common were the vulgar-plaques and guttate in 12 patients (46.15%) and pruritus the most common symptom in 18 (69.23%). The 88.46% of the cases were successfully treated with topical treatment and only 11.54% required more aggressive treatment. We conclude that this age group is frequently affected by psoriasis with prevalence in relation with total visits for the pathology of 22.6%. In the future, it will be interesting to investigate more deeply childhood psoriasis in our city due it important prevalence and to correlate the findings with other local or international studies.(AU)

Obesity in the childhood: a link to adult hypertension.

The rapid increasing prevalence of obesity worldwide represents a serious health hazard. Obesity predisposes to increased risk for diabetes, hypertension, renal failure. Direct mechanisms link visceral adiposity and the atherosclerosis process through the action of adipose-derived proinflammatory cytokines. In particular, hypertension can be considered the most important cardiovascular risk factor linking obesity to the development of cardiovascular disease. Obesity among children and adolescents has also reaching epidemic proportions in the industrialized world. Childhood obesity strongly predisposes to cardiovascular adult mortality. Recent reports documented a tracking of blood pressure from childhood to adulthood and obesity occurring in young age plays a crucial pathogenic role. Indeed, fighting overweight and obesity in the pediatric and adolescent age may prevent the occurrence of adults with hypertension and cardiovascular disease. The main strategies for prevention and treatment of overweight and obesity in childhood, which need to involve community, school and family, are the promotion of lifestyle interventions, including as a correct dietary approach, rich in fruit and vegetables and low-fat dairy products, and physical activity.

The combination of amlodipine/valsartan 5/160 mg produces less peripheral oedema than amlodipine 10 mg in hypertensive patients not adequately controlled with amlodipine 5 mg.

AIMS: To demonstrate the benefit of the combination amlodipine/valsartan 5/160 mg over amlodipine 10 mg, in producing a lower incidence of peripheral oedema for a comparable mean sitting systolic blood pressure (MSSBP) reduction. METHODS: After a 4-week amlodipine 5 mg run-in phase, inadequately controlled hypertension patients (aged > or = 55 years, MSSBP > or = 130 and < or = 160 mmHg) were randomised to receive amlodipine/valsartan 5/160 mg or amlodipine 10 mg for 8 weeks, followed by amlodipine/valsartan 5/160 mg for 4 weeks for all patients. Primary variables were MSSBP change from baseline to week 8 and incidence of peripheral oedema reported as an AE. Resolution of peripheral oedema was assessed 4 weeks after switching patients from amlodipine 10 mg to amlodipine/ valsartan 5/160 mg. RESULTS: At week 8, MSSBP showed greater reduction with amlodipine/valsartan 5/160 mg than amlodipine 10 mg (least square mean: -8.01 vs.-5.95 mmHg, p < 0.001 for non-inferiority and p = 0.002 for superiority). Systolic control, overall BP control and systolic response rate at week 8 were significantly higher with combination than amlodipine 10 mg (34 vs. 26%; 57 vs. 50%; 36.57 vs. 27.77%, respectively). Incidence of peripheral oedema was significantly lower with the combination than amlodipine 10 mg (6.6 vs. 31.1%, p < 0.001). Peripheral oedema resolved in 56% patients who switched from amlodipine 10 mg to the combination, without the loss of effect on BP reduction. CONCLUSION: In non-responders to amlodipine 5 mg, treatment with amlodipine/valsartan 5/160 mg induced significantly less peripheral oedema than amlodipine 10 mg for similar BP reduction. Peripheral oedema resolved in > 50% patients switching from amlodipine 10 mg to the combination.

Endothelial function assessment in complicated hypertension.

A large body of evidence indicates that patients with essential hypertension, and even more those with complicated hypertension, are characterized by endothelial dysfunction characterized by impaired NO availability secondary to oxidative stress production. A dysfunctioning endothelium is an early marker of the development of atherosclerotic changes and can also contribute to cardiovascular events. Vascular reactivity tests represent the most widely used methods in the clinical assessment of endothelial function. In the last two decades, many studies have evaluated the endothelium in hypertensive patients, using different techniques. Several methodologies were developed to study microcirculation (resistance arteries and arterioles) and macrocirculation (conduit arteries), both in coronary and peripheral vascular districts. This review will centre on the most relevant available techniques in the research on endothelial dysfunction in essential hypertension, their advantages and limitations, focusing on available data on endothelial dysfunction which characterizes patients with complicated hypertension. No available test to assess endothelial function has sufficient sensitivity and specificity to be used in clinical practice. Therefore, the optimal methodology for investigating the multifaceted aspects of endothelial dysfunction is still under debate. Only the growing concordant results from different reproducible and reliable methods exploring endothelial function with different stimuli will support and strengthen experimental findings, thus providing conclusive answers in this area of research.

Treatment with low doses of cabergoline is not associated with increased prevalence of cardiac valve regurgitation in patients with hyperprolactinaemia.

INTRODUCTION AND AIM: Dopamine agonists have been reported to increase the risk of cardiac valve regurgitation in patients with Parkinson's disease. However, it is unknown whether these drugs might be harmful for patients with hyperprolactinaemia (HyperPRL). The aim of the study was to evaluate whether HyperPRL patients treated with dopamine agonists had a higher prevalence of cardiac valves regurgitation than that of general population. METHODS AND PATIENTS: One hundred consecutive patients (79 women, 21 men, mean age 41 +/- 13 years) with HyperPRL during treatment with cabergoline were enrolled in an observational case-control study and compared with 100 matched normal subjects (controls). Valve regurgitation was assessed by echocardiography according to the American Society of Echocardiography recommendations. RESULTS: Seven HyperPRL patients (7%) and six controls (6%) had moderate (grade 3) regurgitation in any valve (p = 0.980). All were asymptomatic and had no signs of cardiac disease. Mean duration of cabergoline treatment was 67 +/- 39 months (range: 3-199 months). Mean cumulative dose of cabergoline was 279 +/- 301 mg (range: 15-1327 mg). Moderate valve regurgitation was not associated with the duration of treatment (p = 0.359), with cumulative dose of cabergoline (p = 0.173), with age (p = 0.281), with previous treatment with bromocriptine (p = 0.673) or previous adenomectomy (p = 0.497) in patients with HyperPRL. DISCUSSION: In conclusion, treatment with cabergoline was not associated with increased prevalence of cardiac valves regurgitation in patients with HyperPRL. Mean cumulative dose of cabergoline was lower in patients with HyperPRL than that reported to be deleterious for patients with Parkinson's disease: hence, longer follow-up is necessary, particularly in patients receiving weekly doses > 3 mg.

Planarians, a tale of stem cells.

Planarians possess amazing abilities to regulate tissue homeostasis and regenerate missing body parts. These features reside on the presence of a population of pluripotent/totipotent stem cells, the neoblasts, which are considered as the only planarian cells able to proliferate in the asexual strains. Neoblast distribution has been identified by mapping the cells incorporating bromodeoxyuridine, analyzing mitotic figures and using cell proliferation markers. Recently identified molecular markers specifically label subgroups of neoblasts, revealing thus the heterogeneity of the planarian stem cell population. Therefore, the apparent totipotency of neoblasts probably reflects the composite activities of multiple stem cell types. First steps have been undertaken to understand how neoblasts and differentiated cells communicate with each other to adapt the self-renewal and differentiation rates of neoblasts to the demands of the body. Moreover, the introduction of molecular resource database on planarians now paves the way to renewed strategies to understand planarian regeneration and stem cell-related issues.

C-reactive protein and hypertension: is there a causal relationship?

There is a large body of evidence indicating that inflammation plays a crucial role in all steps characterizing the atherosclerotic process. C-Reactive Protein is a circulating marker of inflammation which recently emerged as a powerful independent determinant of cardiovascular events. Hypertension is closely linked to inflammation. Experimental data and results from cross-sectional studies in humans indicate a relationship between CRP levels and blood pressure. In particular, CRP seems to be related with markers of arterial stiffness, thus suggesting a specific interaction between CRP and systolic blood pressure. However, such observational studies cannot provide any direct evidence for a cause-effect relation. Prospective studies are likely candidates to better define the putative causal relationship on this association. Available results from longitudinal studies are scanty, and do not allow to draw definitive conclusions. Moreover, prospective, placebo-controlled intervention trials documenting that reduction of CRP levels by pharmacological treatment might lead to a reduced risk to develop hypertension are not yet available. Without such crucial information, at the present time the causal connection between inflammation and blood pressure, although regarded as an intriguing possibility, remains undiscovered.

Cloning, tissue expression, and inducibility of CYP 3A79 from sea bass (Dicentrarchus labrax).

Multiple members of the CYP3A subfamily have been identified and intensively studied in mammals as they represent prominent CYP enzymes involved in drug metabolism. Also in fish, some CYP3A genes have been identified by cDNA cloning and immunological techniques, but relatively little is known about their function, distribution, and inducibility. In this study, a novel CYP3A, designated as CYP3A79 was isolated from adult male sea bass, an economically valuable species in fisheries. The sea bass CYP3A79 that was cloned contained an open-reading frame of 1512 bp that encoded a 504 amino acid protein and shared a high-sequence identity with medaka, killifish, and trout CYP3As. Interestingly, CYP3A79 also shares five of six substrate recognition sites (SRS) with the SRS of other fish CYP3As, suggesting an evolutionary conservation of the function of these enzymes. In this fish, we also investigated the expression of CYP3A79 and its susceptibility to induction by various compounds including clotrimazole and dehydroepiandrosterone, two strong ligands of zebrafish PXR. The expression of CYP3A79 mRNA was detected by RT-PCR only in the intestine and liver. The immunoblot analysis by antitrout CYP3A27 confirmed the presence of a CYP3A-like protein in the microsomes of these tissues, but, in addition, a immunoreactive protein with this antibody was also observed in the heart microsomes, suggesting the presence of other CYP3A isoforms in this fish. Accordingly, the southern blot analysis of genomic DNA indicated that multiple CYP 3As may be present in sea bass. All attempts to induce 6beta-testosterone hydroxylase, as a marker of CYP3A79, by dexametasone, 17beta-estradiol, pregnenolone 16alpha-carbonitrile, corticosterone, clotrimazole, and dehydroepiandrosterone failed. On the contrary, the administration of 17beta-estradiol, pregnenolone 16alpha-carbonitrile, and corticosterone strongly inhibited this activity and, in parallel, reduced the expression of CYP3A79 transcript. Thus, the sea bass CYP3A79 appears to be resistant to induction, suggesting that this enzyme and likely other CYP3As are regulated differently compared to those of mammals.

Resolving surface details with reflection and fluorescence video-confocal profilometry.

Video-confocal profilometry has been exploited to characterize reflecting and non-reflecting surfaces in materials with tilted and corrugated areas. An alternative method based on fluorescence detection has been developed and tested to characterize metal surfaces modified by intense laser irradiation. Combined representations of surface topography have been obtained on the basis of both reflectance and fluorescence signals. A discussion of results and problems encountered in reflection and fluorescence based techniques is provided.

[Chronic inflammation and endothelial dysfunction: analysis of a cohort of patients with SLE and UCTD]. / Flogosi cronica e disfunzione endoteliale: analisi di una coorte di pazienti affetti da LES e UCTD.

OBJECTIVE: Cardiovascular complications, mainly caused by an accelerated atherosclerosis, are one of the leading causes of death and disability in patients with systemic autoimmune diseases. Endothelial dysfunction is considered the earliest and reversible step of atherogenesis. Aim of the present study is to investigate endothelial function (EF) in patients with systemic lupus erythematosus (SLE), undifferentiated connective tissue diseases (UCTD) and correlate the results with clinical and laboratory variables. METHODS: EF was assessed on the peripheral microcirculation by the perfused forearm technique that can estimate both endothelium- dependent and endothelium- independent vasodilatation. The same evaluation has been repeated in two patients after the administration of 20 mg of 6-metilprednisolone. RESULTS: Twenty-three female patients with SLE or UCTD, with a follow up of at least 1 year have been studied and compared with 8 healthy controls matched for epidemiological variables and traditional risk factors for cardiovascular disease. A significant reduction both in endothelium dependent than endothelium independent vasodilatation was observed in both patients groups compared with controls. In addition, UCTD patients demonstrated a significant reduction in the nitric oxide pathway compared with controls and SLE patients. Finally, steroid administration induced an improvement of vascular reactivity. CONCLUSIONS: Despite the well documented side effects of chronic corticosteroid therapy, our data might suggest a role for antinflammatory and immunosuppressive therapy in the prevention of premature atherosclerosis in patients with systemic autoimmune diseases.

Subthalamic nucleus stimulation in Parkinson's disease : anatomical and electrophysiological localization of active contacts.

OBJECTIVES: 1 - To assess the anatomical localization of the active contacts of deep brain stimulation targeted to the subthalamic nucleus (STN) in Parkinson's disease patients. 2 - To analyze the stereotactic spatial distribution of the active contacts in relation to the dorsal and the ventral electrophysiologically-defined borders of the STN and the stereotactic theoretical target. METHODS: Twenty-eight patients underwent bilateral high-frequency stimulation of the STN (HFS-STN). An indirect anatomical method based on ventriculography coupled to electrophysiological techniques were used to localize the STN. Clinical improvement was evaluated by Unified Parkinson's Disease Rating Scale motor score (UPDRS III). The normalized stereotactic coordinates of the active contact centres, dorsal and ventral electrophysiologically-defined borders of the STN were obtained from intraoperative X-rays images. These coordinates were represented in a three-dimensional stereotactic space and in the digitalized atlas of the human basal ganglia. RESULTS: HFS-STN resulted in significant improvement of motor function (62.8%) in off-medication state and levodopa-equivalent dose reduction of 68.7% (p < 0.05). Most of the active contacts (78.6%) were situated close to (+/- 1.6 mm) the dorsal border of the STN (STN-DB), while 16% were dorsal and 5.4% were ventral to it. Similar distribution was observed in the atlas. The euclidean distance between the STN-DB distribution center and the active contacts distribution center was 0.31 mm, while the distance between the active contacts distribution center and the stereotactic theoretical target was 2.15 mm. Most of the space defined by the active contacts distribution (53%) was inside that defined by the STN-DB distribution. CONCLUSION: In our series, most of the active electrodes were situated near the STN-DB. This suggests that HFS-STN could influence not only STN but also the dorsal adjacent structures (zona incerta and/or Fields of Forel).

Modì: a new mobile instrument for in situ double-pulse LIBS analysis.

Laser-induced breakdown spectroscopy (LIBS) is a promising technique for in situ elemental analysis. A new mobile instrument for LIBS analysis, developed in a collaboration between Marwan Technology s.r.l. and the Applied Laser Spectroscopy Laboratory in Pisa, is presented, and some applications of it and results from it are outlined. The innovative experimental set-up, based on the use of two suitably retarded laser pulses and a standardless analysis procedure, which overcomes problems related to matrix effects, greatly improves the potential of this technique for accurate quantitative analysis.