Vascular and apoptotic changes in the placode of myelomeningocele mice during the final stages of in utero development

JOAQUIM L. REIS, M.D., PH.D.,1,2 JORGE CORREIA-PINTO, M.D., PH.D.,3,4 MARIANA P. MONTEIRO, M.D., PH.D.,1 MADALENA COSTA, B.SC.,1 AND GROVER M. HUTCHINS, M.D.5 1Department of Anatomy, Abel Salazar Institute for the Biomedical Sciences and Unit for Multidisciplinary Biomedical Research, University of Porto; 2Department of Neurosurgery, Santo António General Hospital; 4Department of Pediatric Surgery, São João Hospital, Porto; 3Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal; and 5Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland Object. Myelomeningocele (MMC) is a primary neurulation defect that is associated with devastating neurological disabilities in affected newborns. To better characterize the in utero neurodegenerative process of MMC, the authors investigated the changes in vascular organization, apoptosis, and the presence of inflammatory cells during gestation by using a mutant mouse model of MMC. Methods. The curly tail/loop tail (ct/lp) mutant mouse model of MMC was chosen to obtain fetuses at different stages of gestation. Mouse fetuses harboring MMC were harvested by caesarean section at embryonic Days 14.5, 16.5, and 18.5 (complete mouse gestation at 19 days, 6 mice/group); littermate fetuses with the same gestational age but without an MMC were used as controls. Samples of the MMC placode or normal spinal cord were stained for immunocytochemical labeling with caveolin antibody (endothelium marker) and activated caspase-3 antibody (apoptosis marker). Samples were morphometrically analyzed with a computer-assisted image analyzer. Results. The MMC mice presented with an increase in vascular density from embryonic Days 16.5–18.5 and an enhanced number of apoptotic cells at embryonic Day 18.5, compared with controls. There were scarce signals of an inflammatory reaction in the MMC placode, as a few infiltrating neutrophils were seen only at embryonic Day 18.5. Conclusions. Fetal placodes in MMC mice showed evidence of increased vascular density since embryonic Day 16.5 and increased apoptosis at embryonic Day 18.5. These new data support the view that in utero changes of the MMC placode, occurring during the last stages of gestation, contribute to the neuropathological manifestations in fullterm newborns with MMC. (DOI: 10.3171/PED/2008/2/8/150

Correlation Between The Ibopamine Provocative Test And The Diurnal Tension Curve In Glaucoma Patients

Purpose: To correlate the ibopamine provocative test with the diurnal tension curve (highest intraocular pressure-IOP and range) in glaucoma. Methods: This is a prospective case series including glaucoma patients from the Federal University of Goiás, Glaucoma Service. Two 2% ibopamine eyedrops were instilled into one or both eyes of each patient, 5 minutes apart. Intraocular pressure was checked before and 30 and 45 minutes after the second ibopamine instillation. Thereafter, the diurnal tension curve of each patient was assessed with five independent measurements (atevery 2:30 hours), from 8:00 o'clock AM to 6:00 o'clock PM. Pearson's correlation coefficient was used to test the linear relation between the intraocular pressure after the ibopamine instillation with the highest intraocular pressure value and the intraocular pressure range in the diurnal curve. Results: Thirty-one eyes from 22 patients were included. There was a significant correlation between the intraocular pressure 30 and 45 minutes after ibopamine instillation and the highest intraocular pressure assessed in the diurnal curve (r=0.356, p=0.04 and r=0.429, p=0.01, respectively). However, no correlation between IOP after the use of ibopamine and the diurnal intraocular pressure range at 30 (r=0.046, p=0.8) and 45 minutes (r=0.109, p=0.5) was observed. Conclusion: The ibopamine provocative test shows a significant corellation with the highest intraocular pressure in the diurnal tension curve in glaucoma patients. However, no correlation was observed with the intraocular pressure range.694477480Armaly, M.F., Water-drinking test. I. Characteristics of the ocular pressure response and the effect of age (1970) Arch Ophthalmol, 83 (2), pp. 169-175Winder, A.F., Siddiqui, A.A., Donovan, H.C., Ocular hypertension and systemic responses to the water-drinking test (1978) Br J Ophthalmol, 62 (6), pp. 414-419Spaeth, G.L., Effects of topical dexamethasone on intraocular pressure and the water drinking test (1966) Arch Ophthalmol, 76 (6), pp. 772-783Harris, L.S., Galin, M.A., Cycloplegic provocative testing (1969) Arch Ophthalmol, 81 (3), pp. 356-358Marchini, G., Babighian, S., Tosi, R., Perfetti, S., Bonomi, L., Comparative study of the effects of 2% ibopamine, 10% phenylephrine, and 1% tropicamide on the anterior segment (2003) Invest Ophthalmol Vis Sci, 44 (1), pp. 281-289McLaren, J.W., Herman, D.C., Brubaker, R.F., Nau, C.B., Wayman, L.L., Ciarniello, M.G., Effect of ibopamine on aqueous humor production in normotensive humans (2003) Invest Ophthalmol Vis Sci, 44 (11), pp. 4853-4858Virno, M., Taverniti, L., De Gregorio, F., Sedran, L., Longo, F., Increase in aqueous humor production following D1 receptors activation by means of ibopamine (1996) Int Ophthalmol, 20 (1-3), pp. 141-146Magacho, L., Lima, F.E., Costa, M.L., Fayad, F.A., Guimaraes, N.L., Avila, M.P., Ibopamine provocative test and glaucoma: Consideration of factors that may influence the examination (2004) Curr Eye Res, 28 (3), pp. 189-193De Gregorio, F., Pecori Giraldi, J., Pannarale, L., Saccucci, S., Virno, M., Ibopamine in glaucoma diagnostics: A new pharmacological provocative test (1996) Int Ophthalmol, 20 (1-3), pp. 151-155Brogliatti, B., Boles Carenini, A., Bogetto, C., Vadala, G., Grignolo, F.M., Boles Carenini, B., Ibopamine test in healthy and glaucomautous eyes: Tonometric and pupillographic study (2000) Acta Ophthalmol Scand Suppl, 78 (232), pp. 13-14Lima, F.E., Guimarães, N.L.D., Santos, L.M., Costa, L.P., Ávila, M.P., Ibopamina tópica na propedêutica do glaucoma (2002) Rev Bras Oftalmol, 61 (2), pp. 109-113Kitazawa, Y., Horie, T., Diurnal variation of intraocular pressure in primary open-angle glaucoma (1975) Am J Ophthalmol, 79 (4), pp. 557-566Sacca, S.C., Rolando, M., Marletta, A., Macri, A., Cerqueti, P., Ciurlo, G., Fluctuations of intraocular pressure during the day in open-angle glaucoma, normal-tension glaucoma and normal subjects (1998) Ophthalmologica, 212 (2), pp. 115-119David, R., Zangwill, L., Briscoe, D., Dagan, M., Yagev, R., Yassur, Y., Diurnal intraocular pressure variations: An analysis of 690 diurnal curves (1992) Br J Ophthalmol, 76 (5), pp. 280-283Zeimer, R.C., Wilensky, J.T., Gieser, D.K., Viana, M.A., Association between intraocular pressure peaks and progression of visual field loss (1991) Ophthalmology, 98 (1), pp. 64-69. , Comment in: Ophthalmology. 1991;98(9):1323Asrani, S., Zeimer, R., Wilensky, J., Gieser, D., Vitale, S., Lindenmuth, K., Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma (2000) J Glaucoma, 9 (2), pp. 134-142. , Comment in: J Glaucoma. 2000;9(6):487-8Anderson, D.R., Patella, V.M., (1999) Automated Static Perimetry, , 2nd ed. St. Louis, Missouri: Year Book MosbyThe relationship between control of intraocular pressure and visual field deterioration (2000) Am J Ophthalmol, 130 (4), pp. 429-440. , The AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS): 7. Comment in: Am J Ophthalmol. 2000;130(4):490-1Armaly, M.F., The visual field defect and ocular pressure level in open angle glaucoma (1969) Invest Ophthalmol, 8 (1), pp. 105-124The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma (1998) Am J Ophthalmol, 126 (4), pp. 498-505. , Collaborative Normal-Tension Glaucoma Study Group. Comment in: Am J Ophthalmol. 1998;126 (4):578-81Am J Ophthalmol. 1999;128(6):776-7Am J Ophthalmol. 1999;127 (5):623-5Am J Ophthalmol. 1999;127(5):625-6Ziai, N., Dolan, J.W., Kacere, R.D., Brubaker, R.F., The effects on aqueous dynamics of PhXA41, a new prostaglandin F2 alpha analogue, after topical application in normal and ocular hypertensive human eyes (1993) Arch Ophthalmol, 111 (10), pp. 1351-135

Структурные изменения в системе гемостаза у больных меланомой кожи на ранней стадии ее развития

Мета дослідження – оцінка показників системи гемостазу у 27 хворих на меланому шкіри. Виявлено подовження активованого часткового тромбопластинового часу, подовження часткового тромбопластинового часу, подовження часу рекальцифікації, зниження рівня антитромбіну III, підвищення рівня розчинних фібрін-мономерних комплексів. Таким чином, мають місце серйозні структурні зміни системного гемостазу - гіпокоагуляція і гіперфібриноліз. Діагностика та корекція цих змін допоможе поліпшити клінічний перебіг і прогноз захворювання.A research aim is an estimation of indexes of the system of hemostasis at 27 patients by the melanoma of skin. Lengthening of the activated partial tromboplastin time, lengthening of partial tromboplastin time, lengthening of time of recalcification, decline of level of antithrombin of III, increase of level of soluble fibrinmonomers complexes is educed. Thus, the serious structural changes in the system of hemostasis - incoagulability and hyperfibrinolysis take place. Diagnostics and correction of these changes will help to improve a clinical flow and prognosis of disease

A step forward

Funding: Authors gratefully acknowledge Fundação para a Ciência e a Tecnologia (FCT) through projects UIDB/00645/2020, UIDB/04138/2020, PTDC/MED-QUI/31721/2017, UIDP/04138/2020 and Lusófona University, ULHT. Authors are also thankful to FCT/MCTES for the financial support to CESAM (UIDP/50017/2020, UIDB/50017/2020), through national funds.Anaplastic thyroid carcinoma (ATC) is a very rare subtype of thyroid carcinoma and one of the most lethal malignancies. Poor prognosis is mainly associated with its undifferentiated nature, inoperability, and failing to respond to the typically used therapies for thyroid cancer. Photothermal Therapy (PTT) entails using light to increase tissues’ temperature, leading to hyperthermia-mediated cell death. Tumours are more susceptible to heat as they are unable to dissipate it. By using functionalized gold nanoparticles (AuNPs) that transform light energy into heat, it is possible to target the heat to the tumour. This study aims to formulate ATC-targeted AuNPs able to convert near-infrared light into heat, for PTT of ATC. Different AuNPs were synthetized and coated. Size, morphology, and surface plasmon resonances band were determined. The optimized coated-AuNPs were then functionalized with ligands to assess ATC’s specificity. Safety, efficacy, and selectivity were assessed in vitro. The formulations were deemed safe when not irradiated (>70% cell viability) and selective for ATC. However, when irradiated, holo-transferrin-AuNPs were the most cytotoxic (22% of cell viability). The biodistribution and safety of this formulation was assessed in vivo. Overall, this novel formulation appears to be a highly promising approach to evaluate in a very near future.publishersversionpublishe

The implementation of radiation technology program in Portugal

The development of ionizing radiation pplications for Industrial purposes in Portugal began near of 1982 with the support of IAEA. The main steps to put forward prior to the implementation were the sitting and the design study in order to build up the facility. Subsequently, the main parameters to be achieved were the construction, the commissioning, the operation, the maintenance and the foreseen decommission. Once a quality system for the gamma facility was established, the following stage is to develop, validate and control the terilization/disinfection process. The research activities carried out in the UTR have been closely related with the main applications of this technology namely, the sterilization of medical devices and pharmaceuticals and other products’ decontamination. Recently, a research Cobalt-60 equipment was upgraded and a LINAC was implemented in order to sustain the R&D. Fundamental and development research is ngoing in order to understand the irradiation mechanisms of action and to apply the technology with safety and quality patterns.The first author would like to thank Gulbenkian Foundation in Portugal and NIC2010 the financial support for the opportunity to participate at NAARRI International Conference

On weak vs. strong universality in the two-dimensional random-bond Ising ferromagnet

We address the issue of universality in two-dimensional disordered Ising systems, by considering long, finite-width strips of ferromagnetic Ising spins with randomly distributed couplings. We calculate the free energy and spin-spin correlation functions (from which averaged correlation lengths, $\xi^{ave}$, are computed) by transfer-matrix methods. An {\it ansatz} for the size-dependence of logarithmic corrections to $\xi^{ave}$ is proposed. Data for both random-bond and site-diluted systems show that pure system behaviour (with $\nu=1$) is recovered if these corrections are incorporated, discarding the weak--universality scenario.Comment: RevTeX code, 4 pages plus 2 Postscript figures; to appear in Physical Review B Rapid Communication

Combination of magnetic resonance cholangiopancreatography and conventional magnetic resonance imaging for the diagnosis of bile duct stenosis

This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the diagnostic accuracy of the magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) for detecting the presence of bile duct stenosis. To evaluate the ability of the MRI and MRCP to determine the site of stenosis. To evaluate the ability of MRI and MRCP to differentiate between benign and malignant bile duct stenosis

Entanglement generation and transfer between remote atomic qubits interacting with squeezed field

A pair of two level atoms A1A2, prepared either in a separable state or in an entangled state, interacts with a single mode of two mode squeezed cavity field while a third atomic qubit B interacts with the second mode of the squeezed field in a remote cavity. We analyze, numerically, the generation, sudden death and revival of three qubit entanglement as a function of initial entanglement of qubits A1A2 and degree of squeezing of electromagnetic field. Global negativity of partially transposed state operator is used to quantify the entanglement of three atom state. It is found that the initial entanglement of two mode field as well as that of the pair A1A2, both, contribute to three atom entanglement. A maximally entangled single excitation Bell pair in first cavity and two mode field with squeeze parameter s=0.64 are the initial conditions that optimize the peak value of three qubit mixed state entanglement. A smaller value of s=0.4 under similar conditions is found to generate a three qubit mixed state with comparable entanglement dynamics free from entanglement sudden death.Comment: 14 pages, 7 figures, sections III and IV merged with section II and analytic expressions moved to Appendices A and B. Figures improved and corrected typo