Non-malignant conjunctival epithelial masses with ocular surface squamous neoplasia-like optical coherence tomography features

International Ophthalmology - To observe and describe the anterior segment optical coherence tomography features of limbally localised non-malignant epithelial mass lesions Thirteen patients (age:...     

Different administration schedules of darbepoetin alfa affect oxidized and reduced glutathione levels to a similar extent in 5/6 nephrectomized rats

Background

The development of erythropoiesis-stimulating agents (ESAs) with extended serum half-lives has allowed marked prolongation of the administration intervals. The level of oxidative stress is increased in chronic kidney disease, and is reportedly decreased after long-term ESA treatment. However, the effect of different dosing regimens of ESAs on oxidative stress has not been elucidated.

Methods

Five-sixths nephrectomized (NX) rats received either 0.4 μg/kg darbepoetin alfa (DA) weekly or 0.8 μg/kg DA fortnightly between weeks 4 and 10. NX animals receiving saline and a sham-operated (SHAM) group served as controls. The levels of oxidized and reduced glutathione (GSSG, GSH) were followed from blood samples drawn fortnightly.

Results

During the follow-up, the ratios GSSG/GSH showed similar trends in both DA groups, levels being significantly lower than those in the SHAM group at weeks 8 and 10. GSSG levels were lower than the baseline throughout the study in all groups except for NX controls. The GSH levels were increased in all three NX groups (weeks 6–10) compared with both the baseline and the SHAM group

Conclusion

Our results suggest that the extent of oxidative stress is similar in response to different dosing regimens of DA in 5/6 NX rats when comparable hemoglobin levels are maintained. These findings remain to be confirmed in chronic kidney disease patients.     

Myocardial Uptake and Release of Substrates in Type II Diabetics Undergoing Coronary Surgery

Objective - Knowledge about myocardial metabolism in diabetic patients is limited, and even more so in association with myocardial ischaemia and cardiac surgery. This study investigates myocardial substrate utilization in type II diabetic patients after elective coronary artery bypass graft surgery (CABG). Design - Myocardial substrate utilization in 10 type II diabetic patients was assessed during the first hours after elective CABG with the coronary sinus catheter technique. Results - No significant myocardial uptake of carbohydrates was observed. Free fatty acids were extracted throughout the study period but uptake was not related to arterial levels. As arterial levels of beta-hydroxybutyric acid tended to increase a significant myocardial uptake emerged. The average extraction rate of beta-hydroxybutyric acid was 31% with a peak of 42%. A comparable extraction rate of glutamate was also found whereas alanine was released from the heart. Conclusion - Free fatty acids were the main source of energy for the heart whereas uptake of carbohydrates was restricted. The high extraction rates of beta-hydroxybutyric acid and glutamate suggest an adaptive role for these substrates during this unfavourable metabolic state for the post-ischaemic diabetic heart.     

Vinpocetine increases cerebral blood flow and oxygenation in stroke patients: a near infrared spectroscopy and transcranial Doppler study.

OBJECTIVE: To investigate the effect of vinpocetine on cerebral blood flow (CBF) in the compromised circulation of a stroke affected hemisphere using transcranial Doppler (TCD) and near infrared spectroscopy (NIRS) methods. METHODS: 43 patients with ischemic stroke were randomized into vinpocetine (VP) and placebo group in a double blind, placebo-controlled study of the effect of a single-dose i.v. infusion of vinpocetine on cerebral blood perfusion and oxygenation. In the VP group 20 mg VP in 500 ml saline, in the placebo group 500 ml saline alone were administered. The concentrations of oxy-, reduced- and total hemoglobin were measured by NIRS frontolaterally on the side of lesion while the mean cerebral blood flow velocity (CBFV), the pulsatility index (PI) and Doppler spectral intensity (DSI) were monitored by TCD in the middle cerebral artery on the same side. Values were averaged for the first 5 min prior to the infusion and for the last 5 min of infusion and they were compared between groups. RESULTS: The concentration of all three chromophores increased during infusion in the VP group (mean dHbT = 1.03, CI(95) = 0.84, P = 0.058; mean dHbO = 0.92, CI(95) = 0.91, P = 0.071; mean dHb = 0.10, CI(95) = 0.21, P = 0.297). The HbT and HbO showed a substantially smaller increase in the placebo group (mean dHbT = 0.31, CI(95) = 0.74, P = 0.22; mean dHbO = 0.57, CI(95) = 0.80, P = 0.094) while the Hb decreased (mean dHb = -0.26, CI(95) = 0.29, P = 0.05). Comparing to the placebo group Hb increased significantly in the VP group (P = 0.027) while the increase of HbO and HbT did not reach the level of significance (P = 0.29 and 0.11). DSI showed a significantly larger increase in the VP than in placebo group (dDSI=25.8 CI(95)=8.8 [VP]; dDSI =3.3, CI(95) = 3.7 [Placebo], P < 0.005). The CBFV and PI did not differ significantly between groups. (dVm = 5.0+/-2.98 cm/s [VP], dVm = 4.1+/-2.57 cm/s [Placebo], P = 0.28; dPI = 0.08 [VP], dPI = 0.09 [Placebo]; P = 0.47). CONCLUSION: VP increases cerebral perfusion and parenchymal oxygen extraction as well. The increased perfusion was indicated by NIRS and by TCD measurement of DSI while conventional velocity and pulsatility measurements failed to detect theses effects. NIRS is a sensitive, feasible method of measuring changes in regional blood flow and tissue oxygenation in the superficial cortex.     

Sevoflurane therapy for life-threatening acute severe asthma: a case report

Introduction

Acute severe asthma is a life-threatening form of bronchial constriction in which the progressively worsening airway obstruction is unresponsive to the usual appropriate bronchodilator therapy. Pathophysiological changes restrict airflow, which leads to premature closure of the airway on expiration, impaired gas exchange, and dynamic hyperinflation (“air-trapping”). Additionally, patients suffering from asthma for a prolonged period of time usually have serious comorbidities. These conditions constitute a challenge during the treatment of this disease. Therapeutic interventions are designed to reduce airway resistance and improve respiratory status. To achieve therapeutic goals, appropriate bronchodilator treatment is indispensable, and mechanical ventilation under adequate sedation may also be required. The volatile anesthetic agent, sevoflurane, meets both criteria; therefore, its use can be beneficial and should be considered.

Case presentation

A 67-yr-old Caucasian male presented with acute life-threatening asthma provoked by an assumed upper airway infection and non-steroidal anti-inflammatory drug antipyretics, complicated by chronic atrial fibrillation and hemodynamic instability. Due to frequent premature ventricular contractions, conventional treatment was considered unsafe and discontinued, and sevoflurane inhalation was initiated via the AnaConDa? (Anaesthetic Conserving Device). Symptoms of life-threatening bronchospasm resolved, and the patient’s respiratory status improved within hours. Adequate sedation was also achieved without any hemodynamic adverse effects.

Conclusion

The volatile anesthetic agent, sevoflurane, is used widely in anesthesia practice. Its utility for treatment of refractory bronchospasm has been appreciated for years; however, its administration was difficult within the environment of the intensive care unit due to the need for an anesthesia machine and a scavenging system. The introduction of the AnaConDa eliminates these obstacles and makes the use of sevoflurane safe and simple. Our case report reveals the potential of sevoflurane as a “two-in-one” (bronchodilator and sedative) drug to treat a severe acute asthma attack.

     

The efficacy of long-term captopril treatment on micro- and macroalbuminuria in hypertensive diabetics

Microalbuminuric [16] and macroalbuminuric [17] hypertensive insulin dependent diabetics were followed up for 4 years after the initiation of captopril therapy to assess the efficacy of ACE inhibitor therapy on albuminuria and blood pressure normalisation. Within the first six months of captopril therapy mean systolic blood pressure decreased in microalbuminuric and macroalbuminuric patients from 168.1±17.6 mmHg to 134.4±12.1 mmHg (19.2±7.1%) and from 177.6±16.8 mmHg to 143.5±12.7 (18.9±6.7%) mmHg, respectively. Mean diastolic blood pressure, similarly, showed a decrease from 91.9±9.1 mmHg to 74.4±10.3 mmHg (19.0±9.4%) in the microalbuminuric and from 95.3±13.7 mmHg to 78.2±7.3 (16.9±9.5%) mmHg in the macroalbuminuric group. After six months of captopril administration albumin excretion rates decreased as well, from 97.4±35.9 μg/min to 51.9±19.9 μg/min (46.9±7.6%) and from 766.7±577.9 μg/min to 365.1±298.4 μg/min (50.4±8.4%) in the micro- and macroalbuminuric groups, respectively. Thereafter, mean albumin excretion rates and blood pressure rose significantly, but at the end of the fourth year they were still significantly lower compared to that of the pretreatment period. After four years, albumin excretion rates were 71.3±29.6 μg/min in the microalbuminuric and 391.2±204.7 μg/min in the macroalbuminuric group. We conclude that ACE inhibitor therapy results in a rapid decrease of albuminuria and blood pressure, and despite a slow gradual increase, the albumin excretion rates and blood pressure values remain significantly lower than the initial values after four years.     

Airway and tissue mechanics in anesthetized paralyzed children

To estimate the mechanical properties of the airways and respiratory tissues, respiratory system impedance (Zrs) was measured with low-frequency forced oscillations in 26 anesthetized, paralyzed children (aged 3 months-10 years) undergoing surgical correction of congenital heart diseases. Zrs was determined from the signals of tracheal flow and pressure between 0.4-12 Hz before surgery at zero mean transrespiratory pressure. The pulmonary (Z(L)) and chest wall (Z(W)) components of Zrs were also determined in 5 children by measuring esophageal pressure. A model containing frequency-independent resistance (R) and inertance (I), and coefficients of tissue-damping (G) and elastance (H), was fitted to the Zrs, Z(L), and Z(W) spectra. The total respiratory parameters normalized to body weights were 82.2 +/- 8.5 (SE) hPa x sec x l(-1) x kg, 0.152 +/- 0.05 hPa x sec(2) x l(-1) x kg, 293.8 +/- 20.0 hPa. l(-1) x kg, and 1,583 +/- 65.5 hPa x l(-1) x kg, for R, I, G, and H, respectively. The measurements of Z(L) and Z(W) revealed the dominance of the lungs in R (91 +/- 4.3%) and I (109 +/- 16%), and the major contribution of the lung parenchyma to G (61 +/- 7.3%) and H (66 +/- 7.4%) of the total respiratory system. It is concluded that anesthesia-paralysis provides an ideal condition for the measurement of low-frequency forced oscillatory impedance and its partitioning into airway and tissue components in mechanically ventilated children. The separation of pulmonary and chest wall mechanics demonstrates that airway properties can be estimated appropriately from Zrs data, while the chest wall may damp the changes in parenchymal properties.     

The in vitro treatment with vitamin D3 is ineffective on the expression of PKC isoenzymes,but decreases further the impaired production of IL-2 in the T lymphocytes of SLE patients

The objective of the study was to investigate the possibility whether the in vitro treatment with vitamin D₃ can restore the impaired expression of protein kinase C (PKC) isoenzymes and IL-2 production in the lymphocytes of patients with systemic lupus erythematosus (SLE). Purified T lymphocytes from 14 patients with SLE and 13 healthy controls were cultured for 48 h in the presence and absence of 1 and 100 nM doses of vitamin D₃. The expressions of various PKC isoenzymes were tested by Western blot analysis, and the amounts of various cytokines were detected by ELISA in the culture supernatants. Neither the low (1 nM) nor the high (100 nM) doses of vitamin D₃ (1α,-25-dihydroxyvitamin) applied in vitro for 48 h were able to restore the decreased expression of PKC isoenzymes in the T cells of SLE patients. However, 100 nM of vitamin D₃ significantly increased the release of IL-10, but suppressed the production of IL-2, IL-6, interferon γ and TNF α in the culture supernatants of both groups. As the low production of IL-2 is one of the main pathologic features of SLE, we recommend to avoid the use of high doses of vitamin D₃ for treatment of lupus patients with vitamin D₃ deficiency.     

Bioreplicated visual features of nanofabricated buprestid beetle decoys evoke stereotypical male mating flights

Recent advances in nanoscale bioreplication processes present the potential for novel basic and applied research into organismal behavioral processes. Insect behavior potentially could be affected by physical features existing at the nanoscale level. We used nano-bioreplicated visual decoys of female emerald ash borer beetles (Agrilus planipennis) to evoke stereotypical mate-finding behavior, whereby males fly to and alight on the decoys as they would on real females. Using an industrially scalable nanomolding process, we replicated and evaluated the importance of two features of the outer cuticular surface of the beetle’s wings: structural interference coloration of the elytra by multilayering of the epicuticle and fine-scale surface features consisting of spicules and spines that scatter light into intense strands. Two types of decoys that lacked one or both of these elements were fabricated, one type nano-bioreplicated and the other 3D-printed with no bioreplicated surface nanostructural elements. Both types were colored with green paint. The light-scattering properties of the nano-bioreplicated surfaces were verified by shining a white laser on the decoys in a dark room and projecting the scattering pattern onto a white surface. Regardless of the coloration mechanism, the nano-bioreplicated decoys evoked the complete attraction and landing sequence of Agrilus males. In contrast, males made brief flying approaches toward the decoys without nanostructured features, but diverted away before alighting on them. The nano-bioreplicated decoys were also electroconductive, a feature used on traps such that beetles alighting onto them were stunned, killed, and collected.Biomimicry of insect visual communication signals has received much recent attention, with growing interest in nanofabrication processes that result in artificially produced structural colors (1) such as those emanating from the ridges on butterfly wing scales (2). The fidelity of the nanoreplication of visual signals with communication value to such organisms has been underexplored, however. Visually induced behavior in arthropods often integrates color and edge-motion detection, with interactions often involving a variety of biotic and abiotic entities, making it difficult to reproduce experimentally (3).Bioreplication of visual signaling structures might be manipulated so as to provide insight into the mechanisms of such signaling processes; however, all currently known examples of bioreplicated nanostructures that have been created to affect behavior involve unicellular movements across particular textured environments (4–7), rather than directed to evoke responses of specialized sensory organs of more complex multicellular organisms. Bioreplicated structures emitting behaviorally effective visual cues also may be useful for such practical purposes as the monitoring and detection of pest species, but the communication efficacy of the bioreplica needs to be validated under field conditions using naturally occurring (i.e., wild) populations.In contrast, biomimicry of chemical signals, such as insect pheromones, has been a burgeoning field for more than half a century. Synthetically reproduced pheromones have been successfully applied under field conditions to manipulate insect behavior for invasive species pest detection, population monitoring of endemic species, and disruption of mating. Thousands of studies have described the essential components of nanoscale levels (nanograms) of semiochemical signals that trigger behavioral responses, such as upwind flight for mating (8), alarm responses (9), and trail following (10). Furthermore, neurophysiological techniques have elucidated how these signals are transduced by peripheral sensory organs (11) and integrated into odor sensations in the higher processing centers of the insect brain (12). In the realm of applied science, these insights have led to trapping protocols for pest population detection, attract-and-kill protocols, and mating disruption (13). Visually attractive features of trapping technologies generally have not been approached with such rigor, however, and are usually optimized by simple manipulations of trap colors without efforts to understand the underlying mechanisms of visual attraction.In an effort to initiate such an approach to manipulation of visual signaling systems, we used an industrially scalable nano-bioreplication technique (14) to produce high-fidelity replicas of the structural features of the cuticle of the hard wing covers (elytra) of an invasive buprestid beetle pest, the emerald ash borer (Agrilus planipennis). This species is a tree-killing pest of Asian origin whose visual signal is emitted by the elytra of a female at rest on an ash leaf in direct sunlight, which triggers attraction of flying males that are patrolling the canopy. Male responses unfold as rapid flights toward the females from heights of up to 2 m, usually terminating with the males alighting directly on the females and attempting to copulate (15). This “paratrooper” descent behavior by flying A. planipennis males in the field can be repeatedly evoked by affixing dead A. planipennis females to ash leaves (15, 16). Furthermore, various other potentially invasive European and North American tree-feeding Agrilus species have been observed performing similar stereotypical inflight descents onto dead beetle decoys affixed to the leaves of preferred host trees (17, 18). Such approaches are often seen to congeneric, heterospecific targets. One such species, the two-spotted oak borer, Agrilus biguttatus, that is similar in size and habits to A. planipennis is known to kill oak trees within its native range in Europe (19), particularly after drought (20) or defoliation events (21).The base colors of many metallic-colored beetles, including buprestid beetles (Fig. 1A), are known to be structurally produced by the repeated alternation of cuticle layers (Fig. 1D) with different refractive indices (22, 23). This periodically multilayered assemblage functions as a quarter-wave Bragg stack reflector in a particular spectral regime (2) and is thus highly effective for creating a color of narrow specificity in sunlight, unlike many naturally occurring pigments. The reflected light is also affected by regular fine-scale topographic features of the surface, including thousands of sharp spicules each emitting green to yellow colors, which are further scattered by numerous spines (Fig. 1 B and C). Many of the physical attributes of the A. planipennis cuticle that produce its attractive visual signal have been replicated by a process that involves the stamping of a polymer quarter-wave Bragg stack reflector with a set of dies cast from the actual elytra of a female A. planipennis (Fig. 2) (14).Open in a separate windowFig. 1.Structural color and surface topography of A. planipennis wings. (A) Optical microscopy showing a dorsal view of the beetle elytron. (B) Higher-magnification optical microscopy showing spines and cilia. (C) Scanning electron micrograph showing a higher-resolution image of the surface topography. (D) Transmission electron micrograph of a cross-section of an elytron, showing four alternating layers of differing refractive indices. (C and D are reprinted with permission from ref. 14.)Open in a separate windowFig. 2.Nano-bioreplicated decoy characteristics. (A) Optical microscopy of the nickel die. (B) Scanning electron micrograph of a nickel die used for bioreplication, showing a similar structure as the A. planipennis surface (Fig. 1), but without the cilia. (C) Optical microscopy of the dorsal view of a nano-bioreplicated A. planipennis decoy that reproduces the surface structure of the beetle and is colored by metallic paint. (A and B are reprinted with permission from ref. 14.)Here we report on direct field observations of A. planipennis and A. biguttatus male behavior toward natural beetle decoys versus three types of synthetic decoys with varying degrees of verisimilitude with respect to the fidelity of bioreplication. These synthetic decoys included: (i) a bioreplicated decoy created by a nanomolding process and colored with a polymer functioning as a Bragg reflector; (ii) another bioreplicated decoy created by a nanomolding process and colored with a metallic green paint; and (iii) a 3D-printed decoy consisting of a smooth polymer surface without a nanomolded bioreplicated surface structure, also colored with green metallic paint. We investigated whether the nanomolding process could create light-scattering patterns similar to those of real decoys by observing light emissions resulting from the application of a white laser to the surfaces of real and synthetic decoys in a dark room. We hypothesized that a sufficient degree of verisimilitude with respect to color and fine-scale topological features of the elytra could be achieved through the bioreplication process to elicit inflight mating approaches and landings similar to those evoked by real beetles. We also incorporated the bioreplicated decoys into a trapping system in which the electroconductive properties of the decoy are used to electrocute male beetles when they approach and alight on the decoys.