Inhaled Liposomal Ciprofloxacin Nanoparticles Control the Release of Antibiotic at the Bronchial Epithelia

The cycle of respiratory tract infection (RTI) and inflammation in patients with chronic obstructive lung diseases, such as cystic fibrosis (CF), periodically develops into exacerbations, where chronic colonization of the airway by bacteria causes severe decline in lung function, leading to increased hospitalization and high mortality rates (1, 2). Current antibiotic inhalation treatments approved for the management of chronic airway infections in cystic fibrosis are limited to tobramycin (TOBI®) and more recently, aztreonam (Cayston®). A major drawback to these localized treatments of RTIs is the rapid absorption and clearance of antibiotics from the lungs requiring multiple daily inhalations of high concentration antibiotic solutions. Hence, liposomal ciprofloxacin nanoparticles were developed to prolong lung residence time of the antibiotics, with the view to enhance antimicrobial activity and reduce the burden of therapy for the patients and their relatives who often have to assist them. Although in vivo studies with aerosolized delivery of liposomal ciprofloxacin have previously been performed on human and animal subjects, in vitro cell models may be better suited to study the transport, interactions of drugs and carrier systems, and drug localization within and on the airway cell epithelium at a molecular level. Therefore, the aim of this study was to investigate the newly developed system allowing nebulized liposomal ciprofloxacin to be delivered directly to the bronchial epithelial surface in an established air interface Calu-3 cell model

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

Gender Differences in Myogenic Regulation along the Vascular Tree of the Gerbil Cochlea

Regulation of cochlear blood flow is critical for hearing due to its exquisite sensitivity to ischemia and oxidative stress. Many forms of hearing loss such as sensorineural hearing loss and presbyacusis may involve or be aggravated by blood flow disorders. Animal experiments and clinical outcomes further suggest that there is a gender preference in hearing loss, with males being more susceptible. Autoregulation of cochlear blood flow has been demonstrated in some animal models in vivo, suggesting that similar to the brain, blood vessels supplying the cochlea have the ability to control flow within normal limits, despite variations in systemic blood pressure. Here, we investigated myogenic regulation in the cochlear blood supply of the Mongolian gerbil, a widely used animal model in hearing research. The cochlear blood supply originates at the basilar artery, followed by the anterior inferior cerebellar artery, and inside the inner ear, by the spiral modiolar artery and the radiating arterioles that supply the capillary beds of the spiral ligament and stria vascularis. Arteries from male and female gerbils were isolated and pressurized using a concentric pipette system. Diameter changes in response to increasing luminal pressures were recorded by laser scanning microscopy. Our results show that cochlear vessels from male and female gerbils exhibit myogenic regulation but with important differences. Whereas in male gerbils, both spiral modiolar arteries and radiating arterioles exhibited pressure-dependent tone, in females, only radiating arterioles had this property. Male spiral modiolar arteries responded more to L-NNA than female spiral modiolar arteries, suggesting that NO-dependent mechanisms play a bigger role in the myogenic regulation of male than female gerbil cochlear vessels

Neuronal Plasticity and Multisensory Integration in Filial Imprinting

Many organisms sample their environment through multiple sensory systems and the integration of multisensory information enhances learning. However, the mechanisms underlying multisensory memory formation and their similarity to unisensory mechanisms remain unclear. Filial imprinting is one example in which experience is multisensory, and the mechanisms of unisensory neuronal plasticity are well established. We investigated the storage of audiovisual information through experience by comparing the activity of neurons in the intermediate and medial mesopallium of imprinted and naïve domestic chicks (Gallus gallus domesticus) in response to an audiovisual imprinting stimulus and novel object and their auditory and visual components. We find that imprinting enhanced the mean response magnitude of neurons to unisensory but not multisensory stimuli. Furthermore, imprinting enhanced responses to incongruent audiovisual stimuli comprised of mismatched auditory and visual components. Our results suggest that the effects of imprinting on the unisensory and multisensory responsiveness of IMM neurons differ and that IMM neurons may function to detect unexpected deviations from the audiovisual imprinting stimulus