phenylephrine-hydrochloride and Central-Nervous-System-Diseases

Topics: Body Height; Body Weight; Bronchial Diseases; Canada; Central Nervous System Diseases; Child, Preschool; Follow-Up Studies; Humans; Hypoxia; Infant; Infant, Newborn; Intellectual Disability; Intubation, Intratracheal; Lung Diseases; Nose; Positive-Pressure Respiration; Respiratory Distress Syndrome, Newborn; Respiratory Function Tests; Respiratory Tract Infections; Trachea; Vocal Cords

Nose-to-brain drug administration along the olfactory and trigeminal nerve pathways offers an alternative route for the treatment of central nervous system (CNS) disorders. The characterization of particle deposition remains difficult to achieve in experiments. Alternative numerical approach is applied to identify suitable aerosol particle size with maximized inhaled doses.. This study numerically compared the drug delivery efficiency in a realistic human nasal cavity between two aerosol drug administration systems targeting the olfactory region: the aerosol mask system and the breath-powered bi-directional system. Steady inhalation and exhalation flow rates were applied to both delivery systems. The discrete phase particle tracking method was employed to capture the aerosol drug transport and deposition behaviours in the nasal cavity. Both overall and regional deposition characteristics were analysed in detail.. The results demonstrated the breath-powered drug delivery approach can produce superior olfactory deposition with peaking olfactory deposition fractions for diffusive 1 nm particles and inertial 10 μm. While for particles in the range of 10 nm to 2 μm, no significant olfactory deposition can be found, indicating the therapeutic agents should avoid this size range when targeting the olfactory deposition.. The breath-powered bi-directional aerosol delivery approach shows better drug delivery performance globally and locally, and improved drug administration doses can be achieved in targeted olfactory region.

Topics: Administration, Inhalation; Administration, Intranasal; Brain; Central Nervous System Agents; Central Nervous System Diseases; Drug Delivery Systems; Humans; Models, Anatomic; Models, Biological; Nasal Sprays; Nose; Particle Size

Satratoxin G (SG), a macrocyclic trichothecene produced by Stachybotrys chartarum, induces apoptosis in cultured neuronal cells as well as nasal olfactory sensory neurons (OSN) in the nose and brain of mice exposed intranasally to this toxin. The purposes of this study were to (1) develop a facile method for production and purification of both SG and its putative biosynthetic precursor, roridin L2 (RL2), from S. chartarum cultures and (2) compare their relative neurotoxicity in vitro and in vivo. Stachybotrys chartarum 29-58-17 was cultured in Fernbach flasks on rice (5 x 10(5) spores/250 g rice) for 4 to 6 wk. Following extraction with acetonitrile, the extract was dried, dissolved in dichloromethane, and subjected to Michel-Miller silica-gel chromatography using a stepwise acetonitrile-dichloromethane gradient with SG and RL2 eluting in the 30 and 40% acetonitrile fractions, respectively. Purification of the two compounds was completed by C18 semipreparative reverse-phase liquid chromatography using an acetonitrile-water gradient, and purity was confirmed by electrospray ionization/collision-induced dissociation (ESI-CID) tandem mass spectroscopy. Although viability significantly decreased in PC-12 neuronal cells treated with 10 to 25 ng/ml of SG, RL2 at concentrations up to 1000 ng/ml was not toxic. Flow cytometry and agarose DNA fragmentation assays revealed that SG at 10 to 25 ng/ml induced apoptotic death in the PC-12 cells, while RL2 at concentrations up to 1000 ng/ml was without effect. In a similar fashion, intranasal exposure of mice (female B6C3F1) to SG at 100 microg/kg body weight (bw) induced marked OSN apoptosis and atrophy of the olfactory epithelium, whereas RL2 at the equivalent dose did not exhibit toxicity. Taken together, an optimized protocol for production and isolation of trichothecenes from S. chartarum cultures is described and further demonstrates that while the macrocyclic SG was neurotoxic in vitro and in vivo, its biosynthetic precursor, RL2, was nontoxic.

Topics: Animals; Central Nervous System Diseases; DNA Fragmentation; Female; Mice; Mice, Inbred Strains; Molecular Structure; Nose; PC12 Cells; Rats; Respiratory Mucosa; Stachybotrys; Trichothecenes

Sinusitis secondary to nasotracheal intubation has not been reported to occur in neurosurgical patients. Over a 1-year period, 11 patients admitted to the Intensive Care/Trauma Unit at St. Paul Ramsey Medical Center developed this entity. The mean age of these patients was 36 +/- 4 years; 7 were trauma victims, 3 had each had a subarachnoid hemorrhage, and 1 had suffered hypertensive hemorrhage. The patients presented with fever of unknown origin (FUO) and evidence of persistent hypermetabolism without an obvious cause. In 8 cases, the diagnosis was not suspected until mucopurulent nasal discharge was noted. Three additional cases were evaluated for suspected sinusitis before the occurrence of discharge. The mean duration of intubation before the diagnosis of sinusitis was 7.8 +/- 1.5 days. The diagnosis was confirmed by sinus films with a Waters view in 7 cases or by computed tomographic scanning in 4 cases and by bacteriological cultures. Two cases involved only the maxillary sinus on the side of intubation; the rest were polysinusites. The organisms involved included gram-positive and gram-negative species; all were polymicrobial with a single organism predominant. Secondary pulmonary involvement was common, and 4 patients revealed a bacteremia consistent with the major sinus organism. One patient developed septic shock. Treatment involved either orotracheal intubation or tracheostomy. This was curative in all cases. It is concluded that neurosurgical patients nasally intubated are at risk for sinusitis, which can have untoward effects such as septicemia or pulmonary infection. A high degree of suspicion will permit early diagnosis and treatment.

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Central Nervous System Diseases; Female; Humans; Intubation, Intratracheal; Male; Middle Aged; Nose; Sinusitis

Rhinophony, which is a change of vocal sound, can appear as a major symptom in many peripheral or central disorders of childhood, adolescence and adulthood. Its investigation, aetiology and management from various points of view are discussed. These are considered broadly as rhinophony aperta (palatal paralysis, functional rhinophony aperta, congenitally short palate); as rhinophony clausa (organic in origin, functional nasal speech); and mixed types of rhinophony. Typical phoniatric problems related to cleft lip and palate are also presented.

Topics: Auscultation; Central Nervous System Diseases; Cleft Lip; Cleft Palate; Diagnosis, Differential; Humans; Jaw Abnormalities; Nose; Palate; Paralysis; Peripheral Nervous System Diseases; Speech Disorders; Voice

Topics: Adult; Brain Neoplasms; Central Nervous System Diseases; Encephalitis; Eyebrows; Humans; Male; Movement Disorders; Neurologic Manifestations; Nose

Topics: Animals; Biological Evolution; Brain Neoplasms; Cats; Central Nervous System Diseases; Cerebral Arteries; Cerebral Cortex; Craniocerebral Trauma; Diagnosis, Differential; Electroencephalography; Encephalocele; Endocrine System Diseases; Female; Genital Diseases, Female; Genital Diseases, Male; Haplorhini; Humans; Hypothalamus; Limbic System; Lymphatic Metastasis; Male; Manometry; Neoplasm Metastasis; Neural Conduction; Neuroectodermal Tumors, Primitive, Peripheral; Neurons; Nose; Nose Neoplasms; Olfaction Disorders; Olfactory Mucosa; Olfactory Nerve; Rabbits; Sensory Receptor Cells; Smell