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With the introduction of probe-confocal laser endomicroscopy (p-CLE), some changes in the patient-care setting are required to maintain high standards of patient safety in endoscopy units. This study focuses on planning for the procedure, patient care, and risk management. After reviewing the literature on this subject, the authors investigate the technical equipment, coordination of a multifunctional team, adequate planning of endoscopic activities, and the introduction of a checklist. As a result of this study, longer procedure times for the preparation of equipment, contrast dye, and drugs were established, as well as the need for patient inter-procedural inter-monitoring; patient identification; monitoring of heartbeat, blood pressure, and oxygen before, during, and after the procedure. Sixty-three patients with gastrointestinal cancer were examined and 14 local adverse events reported. The use of a contrast dye intravenously administered led to the planning of assessments and intraprocedural observations for the correct management of possible side effects, such as anaphylactic shock. Thus, the introduction of p-CLE has a significant effect on the role of the endoscopy nurse both in patient care and in the preparation for the procedure.

We describe here new nanoparticles based on the bioconjugation of penicillin G to squalene in order to overcome severe intracellular infections by pathogen bacteria whose mechanism of resistance arises from the poor intracellular diffusion of several antibiotics. Two different squalene–penicillin G conjugates were synthesized (pH-sensitive and pH-insensitive), and their self-assembly as nanoparticles was investigated through morphology and stability studies. These nanoparticles had a size of 140 ± 10 nm (polydispersity index of 0.1) and a negative charge, and they did not display any supramolecular organization. Furthermore, they were found stable in water and in different culture medium. The cellular uptake and localization of these fluorescently labeled nanoparticles were explored on the macrophage cell line J774 by flow cytometry and confocal microscopy analysis. The squalenoylated nanoparticles were found to be cell internalized through clathrin-dependent and -independent endocytic pathways. Moreover, they induced an improved intracellular antibacterial activity on the facultative intracellular pathogen S. aureus, compared with free penicillin G, despite the absence of co-localization between the bacteria and the nanoparticles in the cells. This study suggests that the bioconjugation of an antibiotic to a squalene template could be a valuable approach for overcoming the antibiotic resistance due to intracellular bacterial infections.

Background: Alginate microspheres represent a useful tool for modified drug delivery. Their preparation is quite easy and is usually based on the gelling properties of the polysaccharide in the presence of divalent ions; nevertheless, microparticles prepared only with calcium alginate show several problems, mainly related to the mechanical stability and to the release that, in most cases, is too fast. To overcome such inconveniences, polymer-coated alginate microspheres and/or appropriately interpenetrating polymer network (semi-IPNs and IPNs) structures formed with alginate and other macromolecules were developed. Objective: This article reports a synthetic overview on the most recent searches carried out on coated alginate microspheres. Methods: After a section focused on the microsphere preparation, this article is divided into several main topics related to the specific polymer that was used as a coating material to provide a rationale in reporting literature data. In the last section, the advantages and disadvantages of the various approaches are discussed and the authors' opinion on perspectives for further studies and novel applications of coated alginate microspheres are reported. Conclusion: Ca2-alginate microparticles could experience a new era if scientists will increase their efforts in developing microparticles with smart properties.

A series of segmented polyurethanes obtained from perfluoropolyether (PFPE) and isophorone diisocyanate (IPDI) were studied by using quantitative thermal analysis. The glass transition behavior of the segregated phases of the segmented copolymers, compared to the corresponding amorphous homopolymers, was characterized in order to determine the dependence of the phase separation on the composition. The glass transition was observed to shift and broaden for both the hydrogenated and the fluorinated phase, reducing the corresponding content in the polymer, and the measured Δcp on the segregated phases deviates from the expected ones according to the homopolymer values. To investigate the effects of the size of the separated domains and of the interfacial constraints on the glass transition behavior, heat capacity measurements were carried out on PFPE models with perfluorinated or methilolic chain ends absorbed on amorphous silica. The chain mobility reduction associated with a nanoscopic confinement is responsible for the effects on the glass transition measured by DSC. This phenomenon seems to rule the observed similar behavior within the polyurethane series investigated in the present work.

ABSTRACTSeveral published studies show a relationship between craniofacial morphology and head posture. The aim of this study was to evaluate the association between cervical lordosis angle and mandibular length from lateral skull radiographs, and to investigate the relationship between mandibular retrusion and cervical lordosis angle decreasing. The sample comprised 70 Caucasian adult women, average 27.4, in skeletal class II and Angle class II. Lateral skull radiographs were obtained in natural head position (mirror position). Ten morphological variables were individuated on tracings. In order to assess errors due to landmark identification, double measurements were made in ten randomly selected radiographs and were compared with Dahlberg's formula. A Sperman's rank correlation test showed a negative correlation (P<0.01) between cervical lordosis and mandibular length (compensatory curvature of the cervical spine) and positive correlation between anterior cranial base and maxillary length (P<0.05). Based upon the cross-sectional method, no conclusion was possible about the mechanism concerning these results. Future longitudinal studies in growing patients should be directed to understanding the extent of environmental and genotype influences on cervical lordosis angle.

A series of perfluoropolyether bis-carboxylic esters was synthesized and their hydrolytic stability investigated. Their formula is ROOCCF2O(CF2CF2O)p(CF2O)qCF2COOR, where p/q = 1.07 and p + q = 2.94. The alkyl group, R, varied both in terms of steric hindrance and electron-withdrawing ability. Kinetic and thermodynamic data were obtained under homogeneous conditions and compared to a fully hydrogenated ester having a closely related structure CH3(CH2)3OOCCH2O(CH2CH2O)nCH2COO(CH2)3CH3, where &nmacr; = 10.6. Neutral ester hydrolysis (NEH) conditions were selected with methyl ethyl ketone as a solvent and a 3–4:1 water/ester ratio. The course of the reaction was monitored by ¹⁹F NMR or ¹H NMR (when R = CH3CH2&bond;). Results indicated that the hydrolysis of fluorinated esters, with alkyl aliphatic substituents, is governed by steric hindrance of the substituents. Two distinctive kinetic regimes were observed. The first one, at low conversion, was characterized by lower kinetic constants and related to true NEH conditions. The second regime appeared at higher conversion when acidic autocatalysis dictated the reaction behavior. This is the only observed mechanism when esters more sensitive to the hydrolysis are considered. In these cases, polar factors prevail over steric considerations. Finally, all fluorinated esters of the class (I) showed a much higher reactivity than the hydrogenated ester whose hydrolysis took place only in the presence of a strong acidic catalyst. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 4266–4280, 2002

The effects of low-intensity, prolonged swimming on functional recovery of the rat heart (Langendorff preparations) from ischaemia-reperfusion (I/R) were investigated. Three groups of rats (120 days old) were used: sedentary rats (S) and rats exercised by a single bout of swimming lasting 5 (E5) or 8 h (E8), respectively. The effect of exercise on the response to I/R was related to an index of oxidative damage such as lipid peroxidation, as well as to the tissue antioxidant capacity and the response of heart tissue to in vitro oxidative stress. The intrinsic performance of E5 Langendorff preparations paced at 220 beats min-1 was also determined. A group of sedentary animals was used for H2O2-treated preparations. The effect of antioxidant treatment on inotropic recovery during reperfusion was studied on preparations from 5 or 8 h swimming vitamin E-treated (EVT5 and EVT8) and 5 or 8 h swimming untreated (EVU5 and EVU8) rats. Hearts from exercised animals displayed a reduced preischaemic inotropism, which in E5 rats was accompanied by an increase in the intrinsic heart rate. The lower intrinsic cardiac inotropism of E5 animals was confirmed in the paced preparations. The reduced contractility found in control hearts after addition of H2O2 to perfusion medium suggested that the low inotropism of E5 and E8 hearts was due to an exercise-induced increase in reactive oxygen species. Inotropic recovery during reperfusion was low in the S hearts, was significantly increased in the E5 hearts, and was again reduced to the S level in the E8 hearts. In the E8 hearts the indexes of cellular damage (LDH release) and oxidative stress increased, and antioxidant capacity decreased, while in E5 hearts there was no evidence of significant changes in such parameters. Performance and reperfusion recovery of hearts from 5 h swimming rats was not affected by vitamin E treatment, while those of hearts from 8 h swimming rats was the highest observed. We suggest that the higher inotropic recovery during reperfusion in the hearts from the E5 rats is related to the negative inotropic effect of exercise. The fall in recovery following the 8 h exercise was instead related to the increased oxidative stress. Experimental Physiology (2001) 86.3, 341-348.

We recently reported that hyperthyroidism affects the heart response to ischemia/reperfusion. A significant tachycardia during reperfusion was associated with an increase in the oxidative stress of hearts from T3-treated animals. In the present study we checked the possible role of nitric oxide (NO) in this major stress induced by the hyperthyroid state. We compared the functional recovery from ischemia/reperfusion of Langendorff preparations from euthyroid (E) and hyperthyroid (H, ten daily intraperitoneal injections of T3, 10 μg/100 g body weight) rats, in the presence and in the absence of 0.2 mM Nω-nitro-L-arginine (L-NNA). At the end of the ischemia/reperfusion protocol (10 min preischemic perfusion, 20 min global ischemia, 30 min reperfusion) lipid peroxidation, antioxidant capacity (CA) and susceptibility to in vitro oxidative stress were determined on heart homogenates. The main effect of hyperthyroidism on the reperfusion functional response was confirmed to be a strong tachycardic response (154% recovery at 25 min reperfusion) accompanied by a low recovery in both left ventricular diastolic pressure (LVDP) and left ventricular dP/dtmax. This functional response was associated with a reduction in CA and an increase in both lipid peroxidation and susceptibility to oxidative stress. Perfusion of hearts with L-NNA per se had small but significant negative chronotropic and positive inotropic effects on preischemic performance of euthyroid rat hearts only. More importantly, L-NNA perfusion completely blocked the reperfusion tachycardic response in the hyperthyroid rats. Concomitantly, myocardium oxidative state (lipid peroxidation, CA and in vitro susceptibility to oxidative stress) of L-NNA perfused hearts was similar to that of E animals. These results suggest that the higher reperfusion-induced injury occurring in hyperthyroid animals is associated with overproduction of nitric oxide.

The possible relation between respiratory capacity and antioxidant capacity and susceptibility to oxidative stress of the liver has been investigated in Rattus norvegicus, Gallus gallus domesticus, Lacerta s. sicula, and Rana esculenta. Accordingly, we measured oxygen consumption and cytochrome oxidase activity, glutathione peroxidase and glutathione reductase activity and overall antioxidant capacity, and lipid peroxidation and response to oxidative stress in vitro in liver. The order of liver oxygen consumption and cytochrome oxidase activity among the different species was rat > chick > lizard > frog. The antioxidant defenses supplied by the combined action of glutathione peroxidase and glutathione reductase were not adapted to the respiratory capacities. In particular, there was no correlation either between the activities of two enzymes or between their activities and oxygen consumption. In contrast, the overall antioxidant capacity of the liver appeared to be related to its oxidative capacity, and the malondialdehyde formation, an indirect measure of lipid peroxidation, was inversely related to antioxidant capacity. The response to oxidative stress in vitro indicated that the liver susceptibility to oxidative challenge is higher in ectothermic than in endothermic species. Such higher susceptibility appeared to depend on both lower antioxidant capacity and higher levels of free radical producing species. This finding is apparently in contrast with a higher content of cytochromes in endotherms, which are able to determine both respiratory characteristics and sensitivity to pro-oxidants. However, it could indicate the existence of species-related differences in the tissue content of either preventive antioxidants or hemoproteins able to trap the radicals produced at their active center. J. Exp. Zool. 284:610–616, 1999.© 1999 Wiley-Liss, Inc.

We studied the changes in the anti-oxidant capacity of tissues, such as heart, liver, and blood in male and female rats, as a parameter for evaluating oxidative stress after either a prolonged (210 min) or an exhausting bout of swimming. Furthermore, we also investigated exercise-induced changes in the electrophysiological properties, measured in vitro, of papillary muscle fibres. Small decreases of anti-oxidant capacities after prolonged exercise [0.10 (SEM 0.04) in heart, 0.43 (SEM 0.19) in liver, 0.22 (SEM 0.05) in blood] and greater decreases after exhausting exercise [0.23 (SEM 0.04) in heart, 0.90 (SEM 0.29) in liver, 0.34 (SEM 0.04) in blood] were found in tissues from the male rats. For the female rats, similar changes were found only in the blood [0.11 (SEM 0.07) and 0.35 (SEM 0.06) for prolonged and exhausting exercise, respectively]. Liver and heart anti-oxidant capacity remained unchanged after prolonged exercise, while after exhausting swimming it underwent a decrease almost the same as found in the male rats, though the swimming time to exhaustion (endurance capacity) was much greater [706 (SEM 10) min and 444 (SEM 32) min for the females and males, respectively]. The duration of the action potential, recorded from papillary muscle fibres, underwent changes related to the decreases in heart anti-oxidant capacity. In fact, the action potential duration (APD) was shorter only in preparations from the male rats after prolonged exercise, but in all preparations after exhausting exercise. After such exercise, the APD was similar for the male and female rats [37.1 (SEM 3.4) ms and 37.0 (SEM 3.6) ms, respectively]. Such a pattern was independent of stimulation frequency, since it was found substantially unchanged when the frequency was increased from 1 to 5 Hz. We concluded that the different susceptibilities to the effects of physical exercise, exhibited by tissues from these male and female rats might have been related to different capacities to oppose oxidative stress effectively.

Three patients affected by the congenital mono-ophthalmia syndrome were submitted to horizontal eye movements recording. The aim was to study the nystagmus and its characteristics, in order to give information that could explain signs and symptoms of the syndrome.Eye movements recording and analysis displayed a jerk nystagmus with a decreasing-velocity exponential slow phase, characteristic of a latent/manifest-latent nystagmus. The intensity of nystagmus decreased in adduction of the viewing eye, and increased in abduction in accordance with Alexander's law. The fast phase was toward the viewing eye. There was no reversal of the fast phase, nor an instability of gaze in the blind eye.

A simple approach to quantitative determination of antioxidant capacity of rat liver homogenate is proposed. It consists of measuring chemiluminescence generated by a suitable system "detector" for OH radicals produced from sodium perborate. The system generating the light signal contained luminal and compounds producing enhancement of light emission, such as sodium benzoate and indophenol. Two different methods, utilizing the same technique of enhanced luminescence, were set up.In a previous work, a parameter b, contained in the equation, which best describes the dependence of the intensity of light emission (E) on liver homogenate concentration (C) (E - a C/exp(bC), was found to be related to the level of antioxidants in the homogenate. Therefore, in the first method, the light emission from several dilutions of both liver homogenates, and homogenate and antioxidant mixtures, stressed with sodium perborate, was detected by a luminometer. The best fitting of data to theoretical equation provided b values, which were introduced in a system of equations relating such values to the antioxidant concentration. The solution of above system supplied the antioxidant concentration in the homogenate in terms of the equivalent concentration of the antioxidant used.In the other method, evaluations of the antioxidant capacity of liver homogenates were obtained by the determination of the ability of 10% homogenates to quench the light emission induced by either peroxidase or cytochrome c in comparison to the ability of antioxidant solutions.Both methods are able to evidence the decrease of the antioxidant concentration of liver homogenates after oxidative stress with ter-butylhydroperoxide. The value of both concentration changes and standard errors indicates that the method using a standard curve obtained with peroxidase, such as catalyst of radical reaction, and deferoxamine, such as antioxidant, is to be preferred.

An enhanced luminescence technique was used to monitor the response of liver homogenates stressed with sodium perborate. Rat liver homogenates were subjected to oxidative stress with sodium perborate, and the light signals, generated by a suitable system, containing luminol and compounds producing enhancement of light emission such as sodium benzoate and indophenol.were detected by a luminometer. The intensity of light emission (E) was found dependent on homogenate concentration (C). When C increased, E at first increased as well and, then, decreased rapidly. The graphic expression of this phenomenon resulted as a curve that can be described by the equation: E = a C/exp(b C). It is proposed that the a value represents the capacity of the tissue to catalyze the production of OH radical species. The b value might be related to the capacity of the tissue to scavenge such radicals, since it increases when homogenates are supplemented with antioxidants and decreases when homogenates are treated with prooxidant. The results obtained by supplementing homogenates with iron containing substances, or using model systems, suggest that cell substances catalyzing the luminescent reaction, such as the hemoproteins, are "scavengers" as well as radical producers. The concentration-emission curve obtained with suitable model system is described by the equation: E = a C/exp(b Ck). It is suggested that.using the k value, information can be obtained on the relative capacity of hemoproteins and antioxidant systems to interact with OH radicals.

The serum thyroid hormone levels [total (TT3) and free (FT3) triiodothyronine] and the heart rates were determined in neonatal rats of different ages (1-5-10 days). Thyroid hormone levels increase gradually in the first 10 days of age. The heart rate, tested at a body temperature of 37°C, also increases during the same period. As the increase in heart rate in this phase of rat life is not due to the catecholamines, it is suggested that such an increase might depend on the increased thyroid hormone activity. On the other hand in congenitally hypothyroid rats the levels of both hormones and heart rates are lower than in normal animals of the same age.The electrophysiological properties of ventricular muscle fibres include a longer action potential, irrespective of stimulation frequency, in younger, naturally hypothyroid animals. The duration of action potential is greater in the congenitally hypothyroid animals, at all ages.These data demonstrate that, as in young and adult rats, the age-related modifications in heart rate, found in neonatal rats, might be due to thyroid dependent modifications of cardiac electrophysiology.

We have studied the effects of in vivo administration of different T3 doses to thyroidectomized rats on electrophysiological properties, measured in vitro, of papillary muscle fibers. The treatment with increasing T3 doses was associated with a significant reduction of the action potential duration up to a dose as large as 25 μg/100 g body weight every second day. The treatment with larger doses of T3 tended to restore the values of the action potential duration present in animals treated with physiological doses (5 μg/100 g body weight every second day).Action potential duration is frequency dependent. As the stimulation rate was increased from 1 to 5 Hz, this duration increased in all groups. However the difference between the rat groups remained significant. The cardiac frequency measured in unanaesthetized rats increased as the T3 doses. Furthermore the intrinsic frequency showed a similar increase, indicating a direct effect of T3 on the pacemaker cells in all thyroid states. The mechanism of this action of the thyroid hormone is not, however clear.

Hyperthermia, with no signs of any underlying infection, may occur in the course of neuroleptic malignant syndrome, fatal catatonia, heat stroke, or malignant hyperthermia. We describe hyperthermia as a complication after discontinuance of antiparkinsonian treatment with levodopa/carbidopa and bromocriptine. Impaired nigrostriatal, hypothalamic, and mesolimbic dopaminergic functions could be involved in pathogenesis.

The authors have determined the serum thyroid hormone levels [total (TT3) and free (FT3) triiodothyronine], the heart weight/body weight ratio and the heart rate of differently aged male rats. The variations of these parameters show a modification of thyroid state as a function of ageing. The authors have also recorded, at about 26°C, resting and action potentials from single cells of papillary muscles isolated from the same groups of rats. The animals in the higher thyroid state exhibited a repolarization speed higher than the other animals. The thyroidectomy, performed on 50 day old rats, and T3 treatment of the thyroidectomized rats give rise to modifications of repolarization speed and then of action potential duration analogous to ones obtained in previous study for animals thyroidectomized at 30 days of age. These data demonstrate that the modifications of heart electrophysiological properties with age, are due fundamentally to thyroid state modifications. The results suggest also that the cardiac chronotropism modifications which the rat undergoes as a function of ageing are due to the changes of levels of thyroid hormone which might exert its effect by modifying the ion channel kinetics as well as the cardiac receptors.

The activity of red blood cell galactose-1-P-uridyl transferase in 22 patients with congenital and infantile cataract and in 18 age-matched controls was investigated. All control subjects examined showed normal enzymatic levels, while 31.8% of patients with congenital and infantile cataract presented a statistically significant reduced enzymatic activity (mean - 2 SD in controls). Twenty-four parents of children with congenital and infantile cataract were also examined. Four parents were affected by congenital cataract and the other 20 showed transparent lenses. The parents were compared with a group of 20 age-matched control subjects examined previously. There was no difference in the average enzymatic activities between the groups. The results suggest that a chronic disorder of galactose metabolism may be involved in the development of congenital and infantile cataract.

Confirming the literature data the authors describe that the heart rate is smaller in the newborn rats than in adult ones and increases until the adult values during the first two weeks of life. On the other hand, the blood thyroid hormone exhibits the same pattern, showing an early postnatal increment. As, according the Adolph's data (1967), the heart rate enhancement is not due to the catecholamines, the authors suppose that such enhancement might conceivably depend on thyroid hormone increment.

Melanoma diagnosed during childbearing period or up to 1 year after delivery is defined as pregnancy-associated melanoma (PAM). There is some evidence that PAM has worse prognosis if compared with melanoma in nonpregnant women, although literature is still inconclusive. Many biological mechanisms could explain this behavior, such as hormonal and immune status, increased lymphangiogenesis but also delay in diagnostic and therapeutic management. If PAM is suspected, a prompt excisional biopsy under local anesthesia can be performed regardless of the gestational period. Conversely, additional staging procedures (such as sentinel lymph node biopsy or imaging) and systemic therapy are still debatable during pregnancy. A multidisciplinary tailored approach should be preferred, together with exhaustive counseling of the mother.

Further investigation of Cape aloe led to the isolation of two new 5-methylchromones. Their structures have been established as 2-acetonyl-7-hydroxy-8-(3-hydroxyacetonyl)-5-methylchromone (2) and 2-acetonyl-8-(2-furoylmethyl)-7-hydroxy-5-methylchromone (3) on the basis of spectroscopic data. A mechanistic hypothesis to account for their occurrence in the drug is presented.