Beyond Fish Oil Supplementation: The Effects of Alternative Plant Sources of Omega-3 Polyunsaturated Fatty Acids upon Lipid Indexes and Cardiometabolic Biomarkers-An Overview.

Cardiovascular diseases remain a global challenge, and lipid-associated biomarkers can predict cardiovascular events. Extensive research on cardiovascular benefits of omega-3 polyunsaturated fatty acids (n3-PUFAs) is geared towards fish oil supplementation and fish-rich diets. Nevertheless, vegetarianism and veganism are becoming more popular across all segments of society, due to reasons as varied as personal, ethical and religious values, individual preferences and environment-related principles, amongst others. Due to the essentiality of PUFAs, plant sources of n3-PUFAs warrant further consideration. In this review, we have critically appraised the efficacy of plant-derived n3-PUFAs from foodstuffs and supplements upon lipid profile and selected cardiometabolic markers. Walnuts and flaxseed are the most common plant sources of n3-PUFAs, mainly alpha-linolenic acid (ALA), and feature the strongest scientific rationale for applicability into clinical practice. Furthermore, walnuts and flaxseed are sources of fibre, potassium, magnesium, and non-essential substances, including polyphenols and sterols, which in conjunction are known to ameliorate cardiovascular metabolism. ALA levels in rapeseed and soybean oils are only slight when compared to flaxseed oil. Spirulina and Chlorella, biomasses of cyanobacteria and green algae, are important sources of n3-PUFAs; however, their benefits upon cardiometabolic markers are plausibly driven by their antioxidant potential combined with their n3-PUFA content. In humans, ALA is not sufficiently bioconverted into eicosapentaenoic and docosahexaenoic acids. However, evidence suggests that plant sources of ALA are associated with favourable cardiometabolic status. ALA supplementation, or increased consumption of ALA-rich foodstuffs, combined with reduced omega-6 (n6) PUFAs intake, could improve the n3/n6 ratio and improve cardiometabolic and lipid profile.

A Biographical Journey Through the History of Ear Reconstruction.

This historical literature review of ear reconstruction differs from much of the published literature in that it focuses on the biographies of the innovators and evangelists of ear reconstruction rather than specific techniques. A biographical account of ear reconstruction demonstrates the importance of surgeons as artists, scientists, technicians, politicians, and most importantly carers of this special and fascinating group of patients who benefit from this technically challenging form of reconstruction.

Formulation parameters and release mechanism of theophylline loaded ethyl cellulose microspheres: effect of different dual surfactant ratios.

Altering the combined hydrophilic-lipophilic balance (CHLB), by varying the ratio of dual surfactants, on formulation parameters and in vitro drug release of ethyl cellulose microspheres was examined. Theophylline, a xanthine bronchodilator was used to model controlled release owing to its narrow therapeutic index. Microspheres were prepared using different ratios of dual surfactant in an emulsion-solvent evaporation process. Drug loading, encapsulation efficiency, particle size distribution, and geometric mean diameters were evaluated. Drug release was evaluated using several kinetic models including zero and first order, Higuchi square root, and Hixson-Crowell. Microspheres presented as mostly spherical particles and diffusional drug release was affected by microsphere construction. For this novel, dual surfactant system the microsphere matrix is a hydrophobic polymer and the release rate may be modulated with variation in ratio of dual surfactants. Dissolution data followed the Higuchi model and supports the formation of a monolithic microsphere matrix that releases theophylline by Fickian diffusion. Dual surfactants for preparation of microspheres are an inadequately studied research area that offers another means to modulate particle size and drug release. For the current study microspheres prepared with surfactant ratios of Span 65: Tween 40 between 3:1 and 2:1 provided the best control of size and drug release.

Transdermal permeation of novel n-acetyl-glucosamine/NSAIDs mutual prodrugs.

The current investigation reports skin permeation of three novel mutual prodrugs (MP) which couple n-acetyl-glucosamine with an NSAID, either ketoprofen or ibuprofen. They were evaluated for transdermal permeation using shed snakeskin, and to our knowledge represent the first MPs synthesized for this purpose, although they also could be used for subcutaneous delivery. MPs are defined as two active drug compounds usually connected by an ester linkage. Glucosamine administration has been linked to damaged cartilage repair, and pain relief in joints afflicted with osteoarthritis. NSAIDs are commonly used orally in transdermal creams or gels for joint pain relief. Two novel compounds we report (MP1 and MP2) covalently link ibuprofen and ketoprofen directly to the amide nitrogen of n-acetyl-glucosamine (NAG); the other compound (MP3) covalently links ibuprofen to the amide nitrogen, using a short chain acetyl linker. Permeability studies show that the ketoprofen mutual prodrug (MP2) permeates shed snakeskin more than three times greater than either ibuprofen derivative, while ethanol markedly increases the permeation for all three. The ketoprofen mutual prodrug appears the most likely candidate for transdermal administration; all three mutual prodrugs may be candidates for subcutaneous injection.

An alternative methodology for the prediction of adherence to anti HIV treatment.

BACKGROUND: Successful treatment of HIV-positive patients is fundamental to controlling the progression to AIDS. Causes of treatment failure are either related to drug resistance and/or insufficient drug levels in the blood. Severe side effects, coupled with the intense nature of many regimens, can lead to treatment fatigue and consequently to periodic or permanent non-adherence. Although non-adherence is a recognised problem in HIV treatment, it is still poorly detected in both clinical practice and research and often based on unreliable information such as self-reports, or in a research setting, Medication Events Monitoring System caps or prescription refill rates. To meet the need for having objective information on adherence, we propose a method using viral load and HIV genome sequence data to identify non-adherence amongst patients. PRESENTATION OF THE HYPOTHESIS: With non-adherence operationally defined as a sharp increase in viral load in the absence of mutation, it is hypothesised that periods of non-adherence can be identified retrospectively based on the observed relationship between changes in viral load and mutation. TESTING THE HYPOTHESIS: Spikes in the viral load (VL) can be identified from time periods over which VL rises above the undetectable level to a point at which the VL decreases by a threshold amount. The presence of mutations can be established by comparing each sequence to a reference sequence and by comparing sequences in pairs taken sequentially in time, in order to identify changes within the sequences at or around 'treatment change events'. Observed spikes in VL measurements without mutation in the corresponding sequence data then serve as a proxy indicator of non-adherence. IMPLICATIONS OF THE HYPOTHESIS: It is envisaged that the validation of the hypothesised approach will serve as a first step on the road to clinical practice. The information inferred from clinical data on adherence would be a crucially important feature of treatment prediction tools provided for practitioners to aid daily practice. In addition, distinct characteristics of biological markers routinely used to assess the state of the disease may be identified in the adherent and non-adherent groups. This latter approach would directly help clinicians to differentiate between non-responding and non-adherent patients.

Accelerated dissolution testing for controlled release microspheres using the flow-through dissolution apparatus.

Theophylline controlled release capsules (THEO-24 CR) were used as a model system to evaluate accelerated dissolution tests for process and quality control and formulation development of controlled release formulations. Dissolution test acceleration was provided by increasing temperature, pH, flow rate, or adding surfactant. Electron microscope studies on the theophylline microspheres subsequent to each experiment showed that at pH values of 6.6 and 7.6 the microspheres remained intact, but at pH 8.6 they showed deterioration. As temperature was increased from 37-57 degrees C, no change in microsphere integrity was noted. Increased flow rate also showed no detrimental effect on integrity. The effect of increased temperature was determined to be the statistically significant variable.

Preparation and evaluation of Eudragit S 100 microspheres as pH-sensitive release preparations for piroxicam and theophylline using the emulsion-solvent evaporation method.

Microencapsulation of the anti-inflammatory drug piroxicam and the anti-asthmatic drug theophylline was investigated as a means of controlling drug release and minimizing or eliminating local side effects. Microspheres of both drugs that are different in the chemical nature and size were successfully encapsulated at a theoretical loading of 25% with the pH sensitive Eudragit S 100 polymer using the emulsion-solvent evaporation method. Solvent composition, stirring rate and the volume of the external phase were adjusted to obtain reproducible, uniform and spherical microspheres. The size distribution of microsphere batches generally ranged from 125-500 microm with geometric means close to 300 microm. Optical light microscopy was used to identify the microsphere shape. Drug loading was determined by completely dissolving the microspheres in an alkaline borate buffer at pH 10. In vitro dissolution studies were carried out on the microspheres at 37 degrees C (+/-0.5 degrees C) at 100 rpm with USP Dissolution Apparatus II using the procedure for enteric-coated products at two successive different pH media (1.2 and 6.5). Both preparations exhibited an initial rapid release in the acidic medium with theophylline showing a larger increase in the amount released during this stage. The drug release was sustained for both preparations at pH 6.5 with theophylline microspheres, showing more extended release. Drug release rate kinetics followed a Higuchi spherical matrix model for both microsphere preparations.

Evaluation of the relationship of the molecular aggregation state of amphotericin B in medium to its genotoxic potential.

This work analyzes the genotoxicity potential, in the G2 phase of the cellular cycle, of an amphotericin B (AmB) commercially available form (Fungizone), and correlates it with the physicochemical properties of this product in aqueous media. The genotoxic studies were performed using peripheral blood lymphocytes from human donors. The chromosome aberrations and mitotic index were determined. Absorption spectra of Fungizone were obtained by dispersion of the stock solution in water for injection at various AmB concentrations, and using different cuvette path lengths for spectrophotometric determination. The absorption spectra of Fungizone in water are concentration dependent. High concentrations of Fungizone present a spectrum with an intense band at 340 nm, characteristic of AmB self-association. Conversely, at low concentrations, the spectra are similar to those obtained with AmB in methanol, with a positive band at 409 nm, assigned to AmB monomeric form. Similarly, the cytogenetic analysis shows an important decrease on the mitotic index, which is also concentration dependent when compared with control. Furthermore, the chromosome aberrations present a small, not statistically significant, increase only at the highest concentration. The results suggest that the Fungizone presents a cytotoxicity similar to membrane pore formation in mammalian cells that depends on the existence of self-associated AmB. In the presence of only monomeric forms, this phenomenon disappears. However, no genotoxicity was observed in this study.

Amphotericin B/emulsion admixture interactions: an approach concerning the reduction of amphotericin B toxicity.

Mixing Fungizone with a fat emulsion used for nutritional purpose (Intralipid or Lipofundin ) was reported to decrease Amphotericin B (AmB) toxicity in clinical use. In an effort to understand the reason for this phenomenon, spectral and morphological analyses were done for the Fungizone and Fungizone /Lipofundin admixture (FLmix). The absorption spectra analyses showed that not only Fungizone but also FLmix presented spectra that were concentration dependent. Moreover, the spectra of FLmix remained stable until the concentration of 5 x 10(-7) M, and only at 5 x 10(-8) M did they become similar in shape to the Fungizone spectra. Morphological studies revealed that even though emulsion droplets with or without Fungizone presented the same particle size, the former was less electron dense compared with Lipofundin alone. These results suggest a kind of association between Fungizoneand Lipofundin that remains over the whole range of concentrations. This hypothesis was confirmed by in vitro studies in which FLmix presented an important selectivity against human and fungal cells compared with Fungizone. These findings suggest that parenteral emulsions should be able to reduce the AmB toxicity probably by changing the AmB self-association state by binding it with emulsion droplets.

Investigation of potential ionic interactions between anionic and cationic polymethacrylates of multiple coatings of novel colonic delivery system.

The objective of this work was to investigate potential interactions between anionic (Eudragit FS) and cationic (Eudragit RL) polymethacrylates of multiple coatings of a novel colonic drug delivery system. Aqueous films of pure polymers Eudragit FS (FS) and Eudragit RL (RL) and their superimposedfilm (FS-RL) were cast on glass slabs. The potential ionic interactions were studied by analysing the dried films using differential scanning calorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), and nuclear magnetic resonance (NMR). The glass transition temperatures (Tg) of pure RL and FS were 60 degrees C and 22 degrees C, respectively; FS-RL showed two distinct glass transitions at 59 degrees C and 24 degrees C in the second heating cycle. In the 13C-MAS spectra of the samples in the solid state, no shifts of the resonance could be detected in the superimposed film compared with the pure polymers. The FT-IR spectra of the superimposed film did not show any significant shift of the bands of the -NMe3+ group of RL and the -COO- function of FS compared with the spectra of the pure polymers. No ionic interactions between anionic and cationic polymethacrylates were revealed by DSC, FT-IR, and NMR.