Search

Cranberry is a fruit originally from New England and currently growing throughout the east and northeast parts of the USA and Canada. The supplementation of cranberry extracts as nutraceuticals showed to contribute to the prevention of urinary tract infections, and most likely it may help to prevent cardiovascular and gastroenteric diseases, as highlighted by several clinical trials. However, aiming to validate the efficacy and safety of clinical applications as long-term randomized clinical trials (RCTs), further investigations of the mechanisms of action are required. In addition, a real challenge for next years is the standardization of cranberry's polyphenolic fractions. In this context, the optimization of the extraction process and downstream processing represent a key point for a reliable active principle for the formulation of a food supplement. For this reason, new non-conventional extraction methods have been developed to improve the quality of the extracts and reduce the overall costs. The aim of this survey is to describe both technologies and processes for highly active cranberry extracts as well as the effects observed in clinical studies and the respective tolerability notes.

A large variation in the severity of disease symptoms is one of the key open questions in coronavirus disease 2019 (COVID-19) pandemics. The fact that only a small subset of people infected with severe acute respiratory syndrome coronavirus 2 develops severe disease suggests that there have to be some predisposing factors, but biomarkers that reliably predict disease severity have not been found so far. Since overactivation of the immune system is implicated in a severe form of COVID-19 and the immunoglobulin G (IgG) glycosylation is known to be involved in the regulation of different immune processes, we evaluated the association of interindividual variation in IgG N-glycome composition with the severity of COVID-19. The analysis of 166 severe and 167 mild cases from hospitals in Spain, Italy and Portugal revealed statistically significant differences in the composition of the IgG N-glycome. The most notable difference was the decrease in bisecting N-acetylglucosamine in severe patients from all three cohorts. IgG galactosylation was also lower in severe cases in all cohorts, but the difference in galactosylation was not statistically significant after correction for multiple testing., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Information about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in HIV-infected individuals is scarce. In this prospective study, we included HIV (human immunodefeciency virus)-infected individuals (people living with HIV [PLWHIV]) with confirmed SARS-CoV-2 infection and compared them with PLWHIV negative for SARS-CoV-2. We compared 55 cases of SARS-CoV-2 infection with 69 asymptomatic PLWHIV negative for SARS-CoV-2 reverse transcription-polymerase chain reaction and/or serology. There was no significant difference between SARS-CoV-2 positive or negative patients for age distribution, gender, time with HIV infection, nadir CD4-cell counts, type and number of co-morbidities, current CD4 and CD8 counts and type of anti-HIV therapy. Positive patients presented with a median of three symptoms (interquartile range, 1-3). Most common symptoms were fever (76%), dyspnea (35%), anosmia (29%) non-productive cough (27%), fatigue 22%), and ageusia (20%). Ten patients (18%) were completely asymptomatic. Four (7.2%) subjects died of coronavirus disease 2019. Factors significantly (P < .05) associated with death included age and number of co-morbidities, while time from HIV infection and lower current CD4 counts were significant only in univariate analysis. HIV-infected individuals are not protected from SARS-CoV-2 infection or have a lower risk of severe disease. Indeed, those with low CD4 cell counts might have worse outcomes. Infection is asymptomatic in a large proportion of subjects and this is relevant for epidemiological studies., (© 2020 Wiley Periodicals LLC.)

During embryonic development, new arteries, and veins form from preexisting vessels in response to specific angiogenic signals. Angiogenic signaling is complex since not all endothelial cells exposed to angiogenic signals respond equally. Some cells will be selected to become tip cells and acquire migration and proliferation capacity necessary for vessel growth while others, the stalk cells become trailer cells that stay connected with pre-existing vessels and act as a linkage to new forming vessels. Additionally, stalk and tip cells have the capacity to interchange their roles. Stalk and tip cellular responses are mediated in part by the interactions of components of the Delta/Notch and Vegf signaling pathways. We have identified in zebrafish, that the transmembrane protein Tmem230a is a novel regulator of angiogenesis by its capacity to regulate the number of the endothelial cells in intersegmental vessels by co-operating with the Delta/Notch signaling pathway. Modulation of Tmem230a expression by itself is sufficient to rescue improper number of endothelial cells induced by aberrant expression or inhibition of the activity of genes associated with the Dll4/Notch pathway in zebrafish. Therefore, Tmem230a may have a modulatory role in vessel-network formation and growth. As the Tmem230 sequence is conserved in human, Tmem230 may represent a promising novel target for drug discovery and for disease therapy and regenerative medicine in promoting or restricting angiogenesis., (© 2017 Wiley Periodicals, Inc.)

Introduction  Testicular microlithiasis (TM), characterized by the presence of intratubular calcifications in a single or both the gonads, is an uncommon entity with unknown etiology and outcome in pediatric and adolescent age. In this study, the results of a multicenter long-term survey are presented. Materials and Methods  From 11 units of pediatric urology/surgery, patients with TM were identified and yearly, followed up in a 7-year period, adopting a specific database. The recorded items were: age at diagnosis, presenting symptoms/associated abnormalities, ultrasonographic finding, surgery and histology at biopsy, if performed. Results  Out of 85 patients, 81 were evaluated yearly (4 patients lost to follow-up). TM was bilateral in 66.6% of the patients. Associate genital abnormalities were present in 90%, more frequently undescended/retractile testis (23.4%) and varicocele (22.2%). TM remained unchanged at 4.7 years follow-up in 77 patients (93.8%) and was reduced in 4 patients after 1 to 5 years of inguinoscrotal surgery. Orchiectomy was performed in three patients (3.7%), one for severe testicular hypoplasia and two for seminoma (2.5%), respectively, concurrent and metachronous to diagnosis of TM. Tumorectomy with parenchymal sparing surgery was performed in a teratoma associated with TM. Conclusion  TM is a controversial entity, often associated with several inguinogenital features, which rarely can recover. Testicular malignancy, although present in TM, has not proven definitively associated to microliths. Proper counseling, yearly ultrasound, and self-examination are long-term recommended., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: The goal of this study was to determine the in vivo functions of the synaptic proteins neurexins and neuroligins in embryonic vascular system development using zebrafish as animal model., Methods and Results: In the present study, we show that the knockdown of the α-form of neurexin 1a induces balance defects and reduced locomotory activity, whereas β-neurexin 1a and neuroligin 1 morphants present defects in sprouting angiogenesis and vascular remodeling, in particular in the caudal plexus and subintestinal vessels. Coinjection of low doses of morpholinos for β-neurexin 1a and neuroligin 1 together or in combination with morpholinos targeting the -heparin--binding isoforms of vascular endothelial growth factor A (encoded by the VEGFAb gene) recapitulates the observed abnormalities, suggesting synergistic activity of these molecules. Similar coinjection experiments with morpholinos, targeting the enzyme heparan sulfate 6-O-sulfotransferase 2, confirm the presence of a functional correlation between extracellular matrix maturation and β-neurexin 1a or neuroligin 1., Conclusions: Our data represent the first in vivo evidence of the role of neurexin and neuroligin in embryonic blood vessel formation and provide insights into their mechanism of action.

Two consecutive children, motor vehicle accident victims, were treated between December 2006 and January 2007. They reported duodenal perforations due to lap-belt action. In the first case (a 9-year-old boy), symptoms became immediately evident after the trauma. Early computerized tomography (CT) scan demonstrated biliaryhemoperitonitis and free sub-diaphragmatic air. At the laparotomy a complete duodenal transection, at the level of duodenal bulb, was found. In the second patient, early X-ray and CT scan revealed no free abdominal air; only the second CT scan, repeated after 48 hours, when general conditions of the girl become critical, demonstrated biliary peritonitis and aerial extraluminal gas image in the right peri-kidney space. At the surgical exploration a duodenal laceration was noted, at the passage between the second and the third duodenal portion, in the postero-lateral wall, with an extension of 6 cm. In both children direct suture of duodenal injury without stoma construction was performed. Not early or late postoperative complications were registered (follow-up: 18 months). In the traumatic duodenal lesions an early diagnosis is not always possible because of the paucity of the clinical signs. Tightened clinical and radiological monitoring of the patient is fundamental in the successive hours to the trauma. Early diagnosis and high level of suspicious rest crucial for better prognosis in this group of patients.

The dysmorphogenic activity of the triazole fungicide triadimefon (FON) has been evaluated using Xenopus laevis development. Embryos, exposed to 500 μM FON during early neurulation phases (stages 13-17, Nieuwkoop and Faber), were allowed to develop until stage 47. Larvae revealed serious craniofacial defects, bent forebrain, and abnormal hindbrain segmentation. CRABP and CYP26 (markers related to retinoic acid homeostasis) gene and protein expression and protein distribution have been evaluated at stage 17 and at the end of the branchial arch morphogenesis (stage 27) by real-time PCR, western blot and whole-mount immunostaining. A significant increase of CYP26 transcript has been observed at both embryonic stages. A co-localization of the two markers has been observed at the cephalic region. Embryos exposed to FON showed abnormal distribution of positive tissues. Due to the strict similarity of these results with those previously described in rodents, a FON-related alteration of mechanism conserved during vertebrate evolution is suggested., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Neuroligins constitute a family of transmembrane proteins localized at the postsynaptic side of both excitatory and inhibitory synapses of the central nervous system. They are involved in synaptic function and maturation and recent studies have linked mutations in specific human Neuroligins to mental retardation and autism. We isolated the human Neuroligin homologs in Danio rerio. Next, we studied their gene structures and we reconstructed the evolution of the Neuroligin genes across vertebrate phyla. Using reverse-transcriptase polymerase chain reaction, we analyzed the expression and alternative splicing pattern of each gene during zebrafish embryonic development and in different adult organs. By in situ hybridization, we analyzed the temporal and spatial expression pattern during embryonic development and larval stages and we found that zebrafish Neuroligins are expressed throughout the nervous system. Globally, our results indicate that, during evolution, specific subfunctionalization events occurred within paralogous members of this gene family in zebrafish.

Identification and characterization of a bovine cDNA and the corresponding gene coding for a novel protein structurally related to Zar1, therefore called Zar1-like, are here reported for the first time. Structure of Zar1-like is similar to Zar1 gene, nevertheless they are located on distinct chromosomes. We demonstrated that the new gene as well as its genomic context are conserved along the whole vertebrate lineage. Analysis of the deduced protein primary structure showed a high conservation, among vertebrates, of the C-terminal region, where the putative presence of both zinc finger motifs and classical nuclear localization signals is also shared with Zar1. Bovine Zar1-like and the only two other available mRNA leader sequences (human and chicken) exhibit a number of upstream AUGs, suggesting that they are likely to be regulated at translational level. Expression patterns of the cattle transcripts show that Zar1-like is absent in early stages of embryo development, whereas Zar1 is expressed in matured oocytes and in in vitro produced pre-implantation embryos. In adult tissues Zar1-like transcript expression appears to be less restricted than Zar1, nevertheless, at least in bovine, both mRNAs are co-expressed in gonads, raising the question of a possible functional link.

This study was conducted in order to analyse gene-expression alterations in rat embryos following exposure to triazoles, using an easy-handling approach. Triazole derivatives have been shown to alter the morphology of cranio-facial structures and to induce abnormalities in hindbrain patterning and neural crest cell migration. Specification of hindbrain segments is regulated by retinoic acid and the hox code. Krox20 was chosen as molecular marker for its specific distribution in the anterior neural tube. In fact, this zinc-finger protein is expressed in rhombomere 3 and 5. Mis-regulation of Krox20 levels have shown to induce severe alterations in the correct patterning of the rhomboencephalon and the derived structures. In order to analyse Krox20 mRNA levels in rat embryos exposed in vitro to the triazole derivative triadimefon, a semi-quantitative approach utilising the competitive RT-PCR was chosen. A lambda phage-based plasmid construct that could compete with target and internal standard gene at the same time during enzymatic reaction was generated. Results were confirmed by real-time RT-PCR analysis on the same samples. Our data show a down-regulation of Krox20 transcript levels after exposure to the triazole derivative, implying a key role of this molecule in the pathogenic pathway induced by triazole exposure.

Prion protein (PrP) and PrP-related proteins have been identified in reptiles, amphibians, and fishes by means of cDNA cloning, genome database searching and comparative genomics. However, no studies have been reported so far on the expression of PrP at the protein level in those animals. This report presents a procedure to obtain and purify recombinant PrP from Xenopus laevis expressed in Escherichia coli as a fusion protein in which mature PrP (residues 21-194) is linked to a 35-amino acid N-terminal extension containing a hexahistidine stretch. The protein was used to raise and purify by affinity chromatography anti-Xenopus PrP polyclonal antibodies which were suitable to detect the presence of PrP in Xenopus brain by Western blot. This is the first report of a positive identification of PrP in amphibian at the protein level. Anti-Xenopus PrP antibodies do not cross react with PrP from different sources (human, bovine, sheep, and turtle). Similarly, Xenopus PrP do not react with anti-turtle PrP(143-248) antibodies.

Objective: To correlate the urge syndrome due to bladder overactivity and the lazy bladder syndrome, demonstrating that, at least in some cases, the lazy bladder may be the final stage of the evolution of an overactive bladder when associated with overactivity of the pelvic floor during micturition., Patients and Methods: From January 1998 to December 1999, 38 children, 30 females and 8 males, 5 to 16 yrs. old (median 7.4 yrs), presenting with urge symptoms and never treated before, have been evaluated with repeated urodynamic investigations. At presentation all the patients underwent complete baseline urodynamics including evaluation of free flow, EMG, cystometrogram, subtracted detrusor pressure and flow/pressure studies. Flow/EMG was repeated every four months during the treatment period and full urodynamic investigation every year., Results: The first urodynamic study showed that 17 patients were affected by pure detrusor overactivity with good detrusor-sphincter co-ordination, while 21 presented both detrusor and pelvic floor muscles overactivity. All the patients have been treated with oxibutinin (0.3-0.5 mg/Kg. in 3 divided doses) and a timed voiding program with the help of a frequency-volume chart. At the end of the study 16 out of the 17 children with pure overactive bladder were cured (94%), while only 12 of the 21 patients with both bladder and sphincter overactivity were clinically and urodinamically normal Nine girls showed a progressive shift towards the development of a lazy bladder syndrome (capacious, hypocontractile bladder with large post-voiding residual and a non relaxing sphincter during micturition). Clinically this shift was signalled by recurrent urinary tract infections., Conclusions: The transition from an overactive bladder to a hypocontractile one has been reported previously, but it has not been extensively investigated in children and its causes are largely hypothetical. In our cases this phenomenon occurred only in girls that, initially showed both detrusor urethral sphincter overactivity, therefore we can reasonably conceive that, at least in some cases, the lazy bladder syndrome may be due to prolonged and repeated high pressure bladder contractions opposed by a non relaxing sphincter that may lead to a progressive loss of the contractile properties of detrusor muscle fibres. The rather rapid shift observed in our patients might have been favoured by the use of anticholinergic medications.

We report evidence from cDNA isolation and expression analysis as well as analyses of genome, expressed sequence tag (EST), cDNA and expression databases for a new gene named SPRN (shadow of prion protein). SPRN comprises two exons, with the open reading frame (ORF) contained within exon 2, and codes for a protein of 130-150 amino acids named Shadoo (Japanese shadow), predicted to be extracellular and GPI-anchored. The SPRN gene was found in fish (zebrafish, Fugu) and mammals (mouse, rat, human). Conservation of order and transcription orientation of two proximal genes between fishes and mammals strongly indicates gene orthology. Sequence comparison shows: a highly conserved N-terminal signal sequence; Arg-rich basic region containing up to six tetrarepeats of consensus XXRG (where X is G, A or S); a hydrophobic region of 20 residues with strong homology to PrP; a less conserved C-terminal domain containing a conserved glycosylation motif; and a C-terminal peptide predicted to be a signal sequence for glycophosphotidylinositol (GPI)-anchor attachment. Fish Shadoos (Sho) show well conserved sequences (identity 54%) over 106 amino acids (zebrafish length), and conservation among the mammalian sequences is very high (identity 81-96%). The fish and mammalian sequences are also well conserved, particularly for zebrafish, to beyond the end of the hydrophobic sequence (identity 41-53%, 78 amino acids, zebrafish length). The overall structure appears closely related to prion proteins (PrPs), although the C-terminal domains of Shos are quite different from those of PrPs, for which conformational changes in mammals are implicated in disease. The structural similarity is particularly interesting given recent reports of three new genes with similarities to PrPs found in Fugu (PrP-like, PrP-461/stPrP-1 and stPrP-2) and other fish, but for which direct evolution to higher vertebrate PrPs is unlikely and for which no other mammalian homologues have been found. Database information indicates expression of SPRN in embryo, brain and retina of mouse and rat, hippocampus of human, and in embryo and retina of zebrafish, and we directly confirmed a strikingly specific expression of the mammalian (human, mouse, rat) transcripts in whole brain. This result together with some common structural features led to the suggestive hypothesis of a possible functional link between mammalian PrP and Sho proteins.

Methods: The correlation between hypertension and related risk factors has been studied in 733 type 2 diabetic patients. Hypertension was more frequent in women (65.35%) than in men (50.35%) (p < 0.0001)., Results: Hypertensive patients showed older age (p < 0.0001) and greater Body Mass Index (BMI) (p < 0.03) than normotensive. In the diabetic group on diet only basal insulinaemia was higher (p < 0.05) in hypertensive than in normotensive diabetic men, but not in women. Such a difference, was not seen in patients of both sexes treated with oral hypoglycaemic agents; besides there was no difference in fasting C-peptide levels between hypertensive and normotensive insulin treated patients. In both sexes hypertension was independently correlated with age, BMI, increased urinary albumin excretion, triglycerides. The strongest correlation was with the family history of hypertension. On the contrary there was no correlation between hypertension and waisthip ratio., Conclusions: In conclusion, the association between hypertension and type 2 diabetes depends on various risk factors, but a relationship with insulin levels is not surely demonstrable.

Methods: The correlation between hypertension and related risk factors has been studied in 733 type 2 diabetic patients. Hypertension was more frequent in women (65.35%) than in men (50.35%) (p < 0.0001)., Results: Hypertensive patients showed older age (p < 0.0001) and greater Body Mass Index (BMI) (p < 0.03) than normotensive. In the diabetic group on diet only basal insulinaemia was higher (p < 0.05) in hypertensive than in normotensive diabetic men, but not in women. Such a difference, was not seen in patients of both sexes treated with oral hypoglycaemic agents; besides there was no difference in fasting C-peptide levels between hypertensive and normotensive insulin treated patients. In both sexes hypertension was independently correlated with age, BMI, increased urinary albumin excretion, triglycerides. The strongest correlation was with the family history of hypertension. On the contrary there was no correlation between hypertension and waist-hip ratio., Conclusions: In conclusion, the association between hypertension and type 2 diabetes depends on various risk factors, but a relationship with insulin levels is not surely demonstrable.

Unlabelled: The aim of this study was to assess the prevalence of various forms of diabetic neuropathy (DN), by clinical and electrophysiological tests, on 374 diabetic patients (66 with type 1 and 308 with type 2 diabetes mellitus) and the concordance between clinical and electroneurological alterations and relative risk factors impact. The overall prevalence of DN, according to the Saint Antonio Conference criteria, was 44.9% (28.88% somatic, 14.44% mixed and 1.60% autonomic) without statistical difference between type 2 and type 1 diabetes (46.43% and 37.88% respectively). In 32.24% of patients nerve conduction velocity (NCV) abnormalities were present together with clinical signs or symptoms of neuropathy, while 12.68% presented only signs and/or symptoms. In addition 9.36% of patients showed alterations of NCV in the absence of clinical signs or symptoms of neuropathy. The most frequent form was asymptomatic (30.21%), followed by symptomatic neuropathy (12.83%); rare was the severe neuropathy. Relative risk increased for diabetes duration > 20 years (p < 0.0001)., In Conclusion: 1) the Saint Antonio Consensus Conference criteria can be considered the most complete test for neuropathy diagnosis; 2) NCV alterations may not be concordant with signs-symptoms of neuropathy; 3) the duration of diabetes seems to be the most important risk factor.

The aim of the study was to evaluate the frequency of Coronary Heart Disease (CHD) and some related risk factors since as hyperlipidemia, hypertension, obesity and visceral distribution of adipose tissue on 733 type 2 diabetic patients in ambulatory care compared to 3500 nondiabetic subjects, matched for age and sex. The frequency of CHD, hyperlipidemias, hypertension, obesity and visceral distribution of adipose tissue was significantly higher in diabetic than in nondiabetic subjects. The risk for CHD was greater in diabetic vs nondiabetic women (4.22) as compared to diabetic vs nondiabetic men (2.6). CHD was mostly associated (over 50% of cases) with hypertension, hyperlipidemia and visceral distribution of adipose tissue. Both cholesterol and triglyceride values, such as CHD frequency, were higher in diabetic patients with poor glycemic control with respect to those with acceptable glycemic, especially in women.

The treatment of NIDDM patients with secondary failure to sulfonylureas is still a debated problem. In this study we compared in NIDDM patients with secondary failure to glyburide, the effect of adding a single, low-dose bed time either NPH or ultralent insulin injection (0.15-0.2 U/kg) to the previously ineffective sulfonylurea treatment. Both NPH and ultralent insulin therapy have been demonstrated to be effective in ameliorating metabolic control in NIDDM patients with secondary failure to sulfonylureas. However, the addition of bed-time ultralent insulin caused a greater and significant decrease in post prandial plasma glucose. In contrast, the average fasting plasma glucose decrease was significantly greater after NPH insulin administration. These results indicate that in NIDDM patients with secondary failure to glyburide bed-time ultralent insulin administration is a better tool to improve the post prandial plasma glucose.

In the past eight years, we observed 23 cases of neonatal urethral obstruction: 15 posterior urethral valves, one urethral polyp, two urethral diverticula, one penile urethra hypoplasia, two syringoceles, one scafoid urethra, one urethral agenesis in Prune Belly syndrome. In most cases a prenatal diagnosis of uropathy had been made by ultrasonography that allowed a faster diagnosis and possibly a long-term better prognosis in those patients in which early treatment reduced postnatal damage. In all patients endoscopic resection was performed under direct view. In 14 of them endoscopic treatment solved the problem, while further surgery on the upper urinary tract was needed in the others. We had no stenotic nor other-short and medium-term complications. The incidence of renal dysplasia is high with posterior urethral valves, while upper urinary tract damages are sensibly less frequent with more distal obstructions.