Smart contact lens: A promising therapeutic tool in aniridia.

OBJECTIVE: The perform pre-clinical testing using optical design tools to simulate the optical quality of a smart artificial iris platform encapsulated in a scleral contact lens. These tools allow us to generate aniridia eye models and evaluate different metrics of visual quality and retinal illumination based on the aperture of the artificial iris based on liquid crystals. METHOD: The OCT imaging technique was used to measure the geometry of the anterior segment in a patient with aniridia and, from these data, the eye model was generated with the Zemax optical design program and specific programs developed in Matlab. Ocular aberrations were calculated and the visual function of the anirida eye model was evaluated in three scenarios: (i) without optical correction, (ii) with correction with a commercial scleral contact lens, and (iii) with correction with an optical lens. Intelligent contact based on artificial iris. RESULTS: Optical quality in patients with aniridia is limited by the magnitude of high-order aberrations. Conventional scleral contact lens design accurately corrects for blur but is unable to compensate for high-order ocular aberrations, especially spherical aberrations. The artificial iris-based smart contact lens design enables virtually all high-order aberrations to be compensated with active control of the pupillary diameter (activation of liquid crystal cells based on ambient lighting). In addition to minimizing high-order aberrations, reducing the pupil size would increase the depth of focus. CONCLUSIONS: This article demonstrates by means of optical simulations the concept of an intelligent artificial iris platform encapsulated in a scleral contact lens and its possible application in patients with aniridia. Furthermore, it allows us to anticipate possible visual results in clinical trials with healthy patients (after application of mydriatic agents) and in patients with aniridia. The results demonstrate a better visual quality and a decrease in retinal illumination.

Smart contact lens: a promising therapeutic tool in aniridia. / Lente de contacto inteligente: una prometedora herramienta terapéutica en aniridia.

OBJECTIVE: To perform pre-clinical testing using optical design tools to simulate the optical quality of a smart artificial iris platform encapsulated in a scleral contact lens. These tools allow us to generate aniridia eye models and evaluate different metrics of visual quality and retinal illumination based on the aperture of the artificial iris based on liquid crystals. METHOD: The OCT imaging technique was used to measure the geometry of the anterior segment in a patient with aniridia and, from these data, the eye model was generated with the Zemax optical design program and specific programs developed in Matlab. Ocular aberrations were calculated and the visual function of the anirida eye model was evaluated in three scenarios: (i) without optical correction, (ii) with correction with a commercial scleral contact lens, and (iii) with correction with an optical lens. intelligent contact based on artificial iris. RESULTS: Optical quality in patients with aniridia is limited by the magnitude of high-order aberrations. Conventional scleral contact lens design accurately corrects for blur but is unable to compensate for high-order ocular aberrations, especially spherical aberrations. The artificial iris-based smart contact lens design enables virtually all high-order aberrations to be compensated with active control of the pupillary diameter (activation of liquid crystal cells based on ambient lighting). In addition to minimizing high-order aberrations, reducing the pupil size would increase the depth of focus. CONCLUSIONS: This article demonstrates by means of optical simulations the concept of an intelligent artificial iris platform encapsulated in a scleral contact lens and its possible application in patients with aniridia. Furthermore, it allows us to anticipate possible visual results in clinical trials with healthy patients (after application of mydriatic agents) and in patients with aniridia. The results demonstrate a better visual quality and a decrease in retinal illumination.

Increased thirst and vasopressin secretion after myocardial infarction in rats.

Impaired regulation of salt and water balance in left ventricular dysfunction and heart failure can lead to pulmonary and peripheral edema and hyponatremia. Previous studies of disordered water regulation in heart failure have used models of low cardiac output with normal cardiac function (e.g., inferior vena cava ligation). We investigated thirst and vasopressin (AVP) secretion in a rat myocardial infarction model of chronic left ventricular dysfunction/heart failure in response to a 24-h water deprivation period. Thirst (implied from water drunk), hematocrit, plasma renin activity, and plasma AVP concentrations increased with water deprivation vs. ad libitum water access. Thirst and plasma AVP concentrations were significantly positively correlated with infarct size after 24-h water deprivation but not under ad libitum water access conditions. The mechanism by which this occurs is unclear but could involve increased osmoreceptor sensitivity, altered stimulation of baroreceptors, the renin-angiotensin system, or altered central neural control.

Endothelin ETA receptor antagonism does not attenuate angiotensin II-induced cardiac hypertrophy in vivo in rats.

1. Angiotensin (Ang) II causes cardiac hypertrophy in vitro and in vivo. It also stimulates the release of endothelin (ET)-1. Endothelin-1 induces hypertrophy of cardiomyocytes in vitro. 2. In the present study, we examined whether the cardiac hypertrophic action of AngII in vivo was mediated by ET-1 via ETA receptors. We also determined whether arginine vasopressin (AVP), another ET-1 stimulator, could cause cardiac hypertrophy in vivo through an ET-1-dependent pathway. 3. In Sprague-Dawley rats (n = 8 per group), we determined whether the orally administered ETA receptor antagonist BMS 193884 could attenuate the cardiac hypertrophic effect of: (i) i.v. AngII infusion at either 100 or 200 ng/kg per min, i.v., for 1 week; (ii) AngII infusion at 100 ng/kg per min, i.v., for 2 weeks; and (iii) AVP infusion at either 2 or 10 ng/kg per min, i.v., for 1 week. Mean arterial pressure and heart rate were also measured. 4. Infusion with AngII for both 1 and 2 weeks increased left ventricular weight. Only AngII infusion at 200 ng/kg per min for 1 week increased blood pressure. Endothelin ETA receptor blockade did not attenuate the left ventricular hypertrophy, even though it reduced the hypertensive effect of AngII. Arginine vasopressin increased blood pressure, but did not cause cardiac hypertrophy. 5. We showed that AngII can cause cardiac hypertrophy through a direct, blood pressure-independent effect on the heart. Endothelin-1 did not mediate the cardiac hypertrophic effect of AngII through ETA receptors. This may indicate the involvement of ETB receptors in this model of cardiac hypertrophy. Arginine vasopressin did not cause cardiac hypertrophy in vivo.

Dynamics of (Cd,Zn)-metallothioneins in gills, liver and kidney of common carp Cyprinus carpio during cadmium exposure.

Cadmium concentrations, (Cd,Zn)-metallothionein (MT) concentrations, MT synthesis and the relative amounts of cadmium bound to (Cd,Zn)-MTs were determined in gills, liver and kidney of common carp Cyprinus carpio exposed to 0, 0.5 microM (0.06 mg.l(-1)), 2.5 microM (0.28 mg.l(-1)) and 7 microM (0.79 mg.l(-1)) Cd for up to 29 days. Cadmium accumulation was in the order kidney > liver > gills. Control levels of hepatic (Cd,Zn)-MT were four times higher compared to those of gills and kidney. No increases in (Cd,Zn)-MT concentrations were observed in liver during the exposure period. In comparison with control carp, (Cd,Zn)-MT concentrations increased up to 4.5 times in kidney and two times in gills. In both these organs, (Cd,Zn)-MT concentrations were linearly related with cadmium tissue levels and with the de novo synthesis of MTs. Hepatic cadmium was almost completely bound to (Cd,Zn)-MT, while percentages of non-MT-bound cadmium were at least 40% in gills and 25% in kidney. This corresponded with a total saturation of (Cd,Zn)-MT by cadmium in kidney and a saturation of approximately 50 and 60% in gills and liver, respectively. The final order of non-MT-bound cadmium was kidney > gills > liver. Our results indicate that cadmium exposure causes toxic effects, which cannot be correlated with the accumulated levels of the metal in tissues. Although cadmium clearly leads to the de novo synthesis of MT and higher (Cd,Zn)-MT concentrations, the role of this protein in the detoxification process is clearly organ-specific and its synthesis does not keep track with cadmium accumulation.

Stress responses and changes in protein metabolism in carp Cyprinus carpio during cadmium exposure.

Stress responses and changes in protein metabolism were studied in common carp Cyprinus carpio exposed to 0, 0.8, 4, and 20 microM cadmium (Cd) over a 29-day period. Blood and other tissue samples were taken after 4 and 29 days of exposure. The highest Cd concentration proved to be lethal to the fish, resulting in 100% mortality after 21 days of exposure. Cd accumulated in the tissues in the following order: kidney>liver>gills. Blood hematocrit, blood hemoglobin, plasma glucose, plasma lactate, and tissue total protein contents were not significantly altered. The concentrations of Cd and zinc (Zn) binding metallothioneins ((Cd, Zn)-MTs) were in the following order=liver>kidney>gills. An increase in (Cd, Zn)-MTs was observed at all exposure concentrations at days 4 and 29 in kidney and at Day 29 in gills. No significant changes in (Cd, Zn)-MT contents were found in liver. The concentrations of free amino acids and the activities of proteases were increased at Day 4 in gills, liver, and kidney of carp exposed to 4 and 20 microM Cd, and in gills and kidney at Day 29 in carp exposed to 4 microM Cd. The observed increases in the activities of aspartate aminotransferase and alanine aminotransferase suggest that the observed proteolysis is intended to increase the role of proteins in the energy production during Cd stress. However, this increased activity of both aminotransferases was not found in gills during exposure to the lethal Cd concentration, indicating that Cd may also cause an inhibitory effect on the activity of these enzymes above a certain level.

Cadmium-binding to transferrin in the plasma of the common carp Cyprinus carpio.

In this study, it was investigated by autoradiography with radioactive cadmium after Western blotting of two-dimensional electrophoresis gels, to which proteins cadmium is mainly bound in plasma of common carp Cyprinus carpio. The obtained results demonstrate that in carp plasma, cadmium is primarily bound to two high molecular weight proteins. Relative small amounts are bound to a protein with M(r) approximately 60000. The other metal-binding protein, with M(r) approximately 70000 and pI approximately 6.7 was identified as transferrin. The conditional equilibrium constants for the binding of cadmium ions to the two metal-binding sites of this protein were calculated as logK(1)=5.40+/-0.12 and logK(2)=4.66+/-0.21, which are comparable to those of human transferrin under the same experimental conditions. Transport of cadmium in plasma of carp was found to be different from that of brown trout Salmo trutta and man, where cadmium is mainly bound to albumin and transferrin. The prominent binding of cadmium to transferrin can be explained by the absence or at least the very low concentrations in which albumin is present in carp plasma.

Hypertension due to a renal renin-secreting tumour.

We report a case of a 25 year old man referred to our department because of a blood pressure of 162/122 mmHg, found during a general physical examination. A renal renin-secreting tumour was found to be the cause of the hypertension. It had a diameter of 4 cm and was enucleated from the right kidney. Subsequently the blood pressure returned to normal levels. Histological examination revealed a hemangiopericytoma.

Continuous imaging of regional blood flow in peripheral vascular disease using Krypton-81m: effect of Ketanserin, a new selective serotonin antagonist.

A new technique consisting of continuous intraarterial infusion of the ultra-short-lived 81mKr for the study of blood flow in patients with severe peripheral vascular disease is described. With the gamma camera high resolution images and typical time activity curves, reflecting local regional blood flow in the feet, could be obtained under resting conditions during reactive hyperemia and administration of vasodilating drugs. Preliminary promising results of Ketanserin, a new selective serotonin antagonist, in patients with impending gangrene and ulcerations are discussed.