Enteral glutamine supplementation reducing infectious morbidity in burns patients: a randomised controlled trial

Purpose

Enteral glutamine supplements have been shown to reduce infectious morbidity in trauma patients, but their effect on patients with burns is not completely studied. The objective of this study was to measure the impact of enteral glutamine supplementation on infectious morbidity and in turn, the hospital-stay in patients with burns.

Methods

Thirty patients with burns were randomly divided into two groups with 15 patients in each, the study (glutamine supplemented) and control group. Patients were randomised to receive either isonitrogenous mixture without glutamine or isonitrogenous mixture with glutamine until complete healing of the burn wound occurred. Incidence of positive blood culture, wound culture, total leucocyte count, hospital-stay and mortality was recorded.

Results

The results showed that the incidence of positive blood culture was considerably reduced in the study group (0.20±0.41) vs. control (0.73±0.96; p = 0.065). The incidence of positive wound culture was significantly reduced in the study group (1.00 ± 1.25) vs. control (3.53 ± 2.47; p = 0.001). In addition, the wound healing was better and hospital-stay days were reduced in the study group (22.73 ± 9.13 days) vs. (39.73 ± 18.27 days; p = 0.003).

Conclusions

These results indicate that enteral glutamine supplementation in adult burn patients could abate the degree of infectious morbidity and reduce hospital-stay.     

Molecular origins of fluorocarbon hydrophobicity

We have undertaken atomistic molecular simulations to systematically determine the structural contributions to the hydrophobicity of fluorinated solutes and surfaces compared to the corresponding hydrocarbon, yielding a unified explanation for these phenomena. We have transformed a short chain alkane, n-octane, to n-perfluorooctane in stages. The free-energy changes and the entropic components calculated for each transformation stage yield considerable insight into the relevant physics. To evaluate the effect of a surface, we have also conducted contact-angle simulations of water on self-assembled monolayers of hydrocarbon and fluorocarbon thiols. Our results, which are consistent with experimental observations, indicate that the hydrophobicity of the fluorocarbon, whether the interaction with water is as solute or as surface, is due to its “fatness.” In solution, the extra work of cavity formation to accommodate a fluorocarbon, compared to a hydrocarbon, is not offset by enhanced energetic interactions with water. The enhanced hydrophobicity of fluorinated surfaces arises because fluorocarbons pack less densely on surfaces leading to poorer van der Waals interactions with water. We find that interaction of water with a hydrophobic solute/surface is primarily a function of van der Waals interactions and is substantially independent of electrostatic interactions. This independence is primarily due to the strong tendency of water at room temperature to maintain its hydrogen bonding network structure at an interface lacking hydrophilic sites.     

Extensive Neonatal Dermatophytoses

Abstract: We report a 25‐day‐old boy who was referred to our dermatology unit for evaluation of extensive annular erythematous lesions on his body. We initially considered the differential diagnoses of candidiasis and neonatal lupus erythematosus but investigations revealed the case as tinea corporis due to a relatively uncommon causative agent, Microsporum gypseum. To the best of our knowledge it is the first case of extensive neonatal dermatophytoses caused by this organism. The possible causes and the role of steroids in producing the clinical picture in our patient are discussed.     

Corneal fibroblasts respond rapidly to changes in local mechanical stress

PURPOSE: To investigate the response of corneal fibroblasts to local changes in extracellular matrix (ECM) tension. METHODS: Rabbit and human corneal fibroblasts were plated inside fibrillar collagen matrices. After 18 to 72 hours, a glass microneedle was inserted into the ECM and either pushed toward a cell to reduce local tension, or pulled away to increase tension. Time-lapse differential interference contrast (DIC) imaging was performed both before and after needle micromanipulation. ECM displacements were quantified, and strain maps were generated by finite element modeling. In some experiments, cells were treated with the Rho-kinase inhibitor Y-27632 either 30 minutes before, or 1 hour after they were pushed with the microneedle. Changes in focal adhesion organization were also evaluated in a subset of cells expressing green fluorescent protein (GFP)-zyxin, by simultaneous fluorescent and DIC imaging. RESULTS: Pulling on the ECM resulted in initial cell elongation, followed by disengagement and retraction of pseudopodia. In contrast, pushing the ECM toward a cell induced rapid shortening (contraction), presumably since existing cellular forces were no longer counterbalanced by ECM tension. Pseudopodial extension (spreading) was then observed at both ends of the cell. The ECM was pulled inward during this secondary spreading, and rapid turnover of focal adhesions was observed along extending pseudopodia. Preincubation with Y-27632 or cytochalasin D blocked both the initial contractile and secondary spreading responses. CONCLUSIONS: Overall, the data suggest that corneal fibroblasts actively respond to increases or decreases in local matrix stress in an attempt to maintain tensional homeostasis (constant tension), and that this response may be mediated by Rho and/or Rac.     

Saccadic localization in the presence of cues to three-dimensional shape

Saccades directed to simple two-dimensional (2D) target shapes under instructions to look at the target as a whole land near the center of gravity (COG) of the shape with a high degree of precision (He & Kowler, 1991; Kowler & Blaser, 1995; McGowan, Kowler, Sharma, & Chubb, 1998; Melcher & Kowler, 1999; Vishwanath, Kowler, & Feldman, 2000). This pattern of performance has been attributed to the averaging of visual signals across the shape. Natural objects, however, are three-dimensional (3D), and the shape of the object can differ dramatically from its 2D retinal projection. This study examined saccadic localization of computer-generated perspective images of 3D shapes. Targets were made to appear either 2D or 3D by manipulating shading, context, and contour cues. Average saccadic landing positions (SD approximately 10% eccentricity) fell at either the 2D or 3D COG, and occasionally in between, depending on the nature of the 3D cues and the subject. The results show that saccades directed to objects are not compelled to land at the 2D COG, but can be sensitive to other visual cues, such as cues to 3D structure. One way to account for these results, without abandoning the averaging mechanism that has accounted well for performance with simple 2D shapes, is for saccadic landing position to be computed based on averaging across a weighted representation of the shape in which portions projected to be located at a greater distance receive more weight.     

Bioadhesive tablets for controlled transdermal delivery of drugs

Transdermal bioadhesive tablets were formulated by the direct compression method and evaluated. Carboxyfluorescein (CF) was used as a model permeant. The compression parameters were kept consistent and the composition of the formulation was varied to alter the release rate of the drug from the formulations. The dosage form was evaluated for physicochemical, adherence, and in vitro diffusion parameters. The transdermal flux of the drug decreased with the increasing ratio of Ethyl cellulose (EC)/hydroxypropyl cellulose (HPC). The test formulations were subjected to pharmacokinetic studies in mice. The formulations were able to maintain a steady state plasma concentration up to 12 hours. They were found to be safe for transdermal use as interpreted from skin irritation studies carried out on rabbits.     

Procoagulant activity of Calotropis gigantea latex associated with fibrin(ogen)olytic activity.

The latex of Calotropis gigantea is a rich source of useful components that has medicinal properties and one of the main applications is in controlling bleeding. The crude latex extract contained many proteins, which are highly basic in nature and exhibited strong proteolytic activity. The crude extract hydrolyses casein, human fibrinogen and crude fibrin clot in a dose-dependent manner. The hydrolyzing activity was completely inhibited by IAA indicating they belong to the super family, cysteine proteases. Crude extract hydrolyses Aalpha, Bbeta and gamma subunits of fibrinogen. Among all the subunits the preferential subunit to get hydrolyzed was Aalpha followed by Bbeta and gamma subunit is highly resistant and hydrolyzed at higher protein concentration or over a prolonged incubation time. The crude extract hydrolysis crude fibrin clot strongly compared to trypsin and papain. Pharmacologically the crude extract is hemorrhagic and induces skin hemorrhage at >75 microg and reduces the coagulation time of citrated plasma from 150 to 47 s and promotes blood coagulation. Procoagulation and blood clot hydrolysis are important in wound healing process. This is due to unique cysteine proteases of plant latex and is responsible for the pharmacological actions observed in folk medicine.     

Edema-inducing activity of phospholipase A2 purified from human synovial fluid and inhibition by aristolochic acid

A neutral-active, Ca²⁺-dependent phospholipase A₂ (PLA₂) purified 11,000-fold from human synovial fluid (HSF) induced edema when injected into the mouse foot pad. The edema produced by HSF-PLA₂ was dose-dependent and was positively correlated with the dose-dependent in vitro expression of PLA₂ activity. Maximum edema was achieved within 45 min after the injection and persisted for atleast 6 h. Aristolochic acid [8-methoxy-6-nitrophenanthro(3,4-d)-1,3-dioxole-5-carboxylic acid], a major chemical component derived from various species ofAristolochia plant, produced a dose-dependent inhibition of in vitro phospholipid hydrolysis by HSF-PLA₂, porcine pancreatic PLA₂, snake venom (Naja naja) PLA₂, and PLA₂ isolated from human platelet. The sensitivity of these PLA₂s to inhibition by aristolochic acid varied markedly: HSF-PLA₂>N.naja PLA₂>human platelet PLA₂>porcine pancreatic PLA₂. The inhibition of HSF-PLA₂ by aristolochic acid was independent of substrate concentration (18–144M and Ca²⁺ concentration (0.1–4.0 mM). These observations indicate that inhibition of HSF-PLA₂ by aristolochic acid may result from direct interaction with the enzyme. When aristolochic acid was mixed with HSF-PLA₂ and then injected into the mouse foot pad, edema was inhibited in a dose-dependent manner and was positively correlated with in vitro inhibition of PLA₂ activity. Alkylation of HSF-PLA₂ withp-bromophenacyl bromide concomitantly inhibited both enzyme and edema-inducing activity. These results clearly demonstrate that the neutral-active, Ca²⁺-dependent PLA₂ isolated from human synovial fluid is proinflammatory and that catalytic activity is positively correlated with in vivo proinflammatory effects.     

Synthesis and evaluation of trimethoxyphenyl isoxazolidines as inhibitors of secretory phospholipase A2 with anti-inflammatory activity

A series of trimethoxyphenyl isoxazolidine derivatives, 5a(i-v) and 5b(i-v), bearing different constituents at the 5th position of the isoxazolidine ring were synthesized and evaluated in vitro and in vivo for their inhibitory activity against purified group I and II phospholipase A2 (PLA2) enzymes from snake venom and human inflammatory synovial fluid. Irrespective of modification to the pharmacophore (isoxazolidine ring), they exhibited greater specificity for group II PLA2. The length of alkyl or aryl group at the 5th position, which alters the hydrophobic and aromatic property, was responsible for enhancing the inhibition towards PLA2 enzymes. All of the compounds quench the fluorescent property of the purified PLA2 enzyme, and quenching increases with the increase in length of alkyl or aryl group. The inhibitory effect of compounds appeared to be due to the direct interaction of compounds with the enzyme. Inhibition is substrate-dependent, and the inhibitor likely competes with the substrate for the same binding site of the enzyme. The IC50 value for the most potent interacting inhibitor 5b(v) was 54.8 microM. The most active interacting compounds 5a(v) and 5b(v) from in vitro inhibition of PLA2 activity showed similar potency in in vivo neutralization of PLA2-induced mouse paw edema and hemolytic activity.