Effect of chronic treatment with octreotide nasal powder on serum levels of growth hormone, insulin-like growth factor I, insulin-like growth factor binding proteins 1 and 3 in acromegalic patients

Octreotide nasal powder is a delivery system of the somatostatin analogue developed to overcome the inconvenience of repeated subcutaneous administrations. Eight patients with clinically active acromegaly were treated for three months with octreotide nasal powder which was administered at the initial dosage of 0.125 mg tid, doubling the dosage up to 2 mg tid in order to obtain a mean GH value below 5 micrograms/l during 8 daytime hours. In 4 of these patients, treatment was prolonged till the sixth month. Blood samples were taken on days 15, 29, 43, 55, 90, 120, 150, 180 for GH, IGF-I, IGFBP-3, IGFBP-1 and insulin measurements. Before treatment, mean daytime GH and morning IGF-I serum levels were both increased but not correlated with each other. Serum IGFBP-3 levels were higher than normal and positively correlated with those of GH, IGF-I and insulin. Insulin levels were elevated and positively correlated with those of GH but not with those of IGF-I and IGFBP-1. Serum IGFBP-1 levels were in the low normal range and not correlated with any of the other parameters. Treatment with octreotide nasal powder induced in all patients a marked decrease of GH which lowered below 5 micrograms/l in 7/8 patients and IGF-I levels, which fell within the normal range in 1 patient. Serum IGFBP-3 and insulin concentrations decreased by 26% and 71%, respectively, and those of IGFBP-1 underwent an only transient increase in 5/8 patients. Opposite changes of insulin and IGFBP-1 levels, with a decrease of the former followed by an increase of the latter were noted during the 8 hours following an octreotide nasal insufflation. During chronic octreotide treatment, positive correlations were found between GH and IGF-I, GH and IGFBP-3, IGF-I and IGFBP-3, insulin and IGFBP-3 and insulin and IGF-I. An improvement of the clinical picture was registered in all patients after a few days of octreotide nasal powder administration. Treatment was well tolerated, with only mild side effects and no significant changes in the nasal mucosa, and the patients' compliance was excellent.     

The Resident Assessment Instrument (RAI): promise and pitfalls

The nasal bioavailability of oxymorphone HCI was determined. Rats were surgically prepared to isolate the nasal cavity, into which a solution of oxymorphone was administered. A reference group of rats was administered oxymorphone HCl intravenously. Plasma oxymorphone concentrations were determined by HPLC. Nasal absorption was rapid, nasal bioavailability was 43%, and the iv and nasal elimination profiles were similar. Oxymorphone HCI appears to have the solubility, potency, and absorption properties required for efficient nasal delivery, which is an alternative to injections.     

Nasal delivery of peptides: an in vitro cell culture model for the investigation of transport and metabolism in human nasal epithelium

We investigated the transport- and metabolism properties of three peptides in monolayers of human nasal epithelial cells. The effective permeability coefficients of thyrotropin-releasing hormone, met-enkephalin and human recombinant insulin were found to be 4.5, 4.4 and 0.4 x 10(-7) cm/s, respectively. The permeability was inversely proportional to the molecular weight and one order of magnitude lower than in excised nasal mucosa of rabbits. The metabolic cleavage of thyrotropin-releasing hormone (TRH) to the free acid by cytosolic prolyl-endopeptidase was also detected in human nasal cell monolayers, suggesting that ca. 10% of the total amount of TRH is transported via a transcellular pathway. Met-enkephalin is a substrate for aminopeptidases, located on the apical membrane of nasal epithelial cells. Metabolites and enzyme activity are comparable with literature data. Our studies demonstrate that not only morphological, but also functional properties of human nasal epithelial cells are preserved under in vitro conditions. Such a cell culture model based on human nasal cells could be beneficial for the characterization of peptide transport on a cellular level and for investigation of the absorption enhancer mechanism. Further studies are necessary, however, to establish correlations between in vitro permeabilities in cell cultures and nasal drug absorption in animals and humans.     

Chitosan and its use as a pharmaceutical excipient

Chitosan has been investigated as an excipient in the pharmaceutical industry, to be used in direct tablet compression, as a tablet disintegrant, for the production of controlled release solid dosage forms or for the improvement of drug dissolution. Chitosan has, compared to traditional excipients, been shown to have superior characteristics and especially flexibility in its use. Furthermore, chitosan has been used for production of controlled release implant systems for delivery of hormones over extended periods of time. Lately, the transmucosal absorption promoting characteristics of chitosan has been exploited especially for nasal and oral delivery of polar drugs to include peptides and proteins and for vaccine delivery. These properties, together with the very safe toxicity profile, makes chitosan an exciting and promising excipient for the pharmaceutical industry for present and future applications.     

Delivery of nasal powders of beta-cyclodextrin by insufflation

PURPOSE: Delivery of nasal powders of granulated beta-cyclodextrin by insufflation was studied in order to find the relationship between powder properties and delivery behavior. METHODS: Three nasal powder formulations, prepared by granulating beta-cyclodextrin with different binders, were delivered from a powder insufflation device, in which the dose to be emitted was loaded in a gelatin capsule. The delivery sequence of powder was recorded and characterized using an image analysis program. RESULTS: Particle size was the main parameter affecting nasal powder delivery, both as to the amount of dose sprayed and the aspect of cloud produced. Between 50-150 mu m of particle size a substantial change in delivery behavior of powders was observed. Powder of around 100 mu m in size showed useful insufflation characteristics for nasal delivery. Bioavailability of nasal formulations of progesterone/beta-cyclodextrin powders was discussed in term of delivery behavior. CONCLUSIONS: The formulation approaches for improving nasal delivery of powders require the use of size optimized carriers. Insufflation of powders over 50 mu m can favour the particle deposition by impaction, whereas for powders below 50 mu m, deposition by sedimentation is moved. beta-cyclodextrin is a suitable carrier for achieving high systemic availability following nasal administration of powder formulations.     

Permeation of polysucrose 15000 across the human nasal mucosa in vivo

Studies of the nasal permeation of small molecules (< 1000 Da) have yielded important information about the integrity of the human airway mucosa in health and disease. In this study, we used a much larger tracer molecule, polysucrose (PS) 15,000 (approx. 14,700 Da), to predict the mucosal permeation of inhalational allergens. PS 15,000 (50 mg/ml; 15 ml), with or without a detergent type of permeation enhancer (dioctyl sodium sulfosuccinate 10 mg/ml), was maintained for 15 min in one nasal cavity of 12 healthy nonatopic subjects by employment of a nasal-pool device. Permeation as determined by the 24-h urine recovery of PS (micro-ELISA analysis assay) was expressed as percentage of nasal instillate. Mean baseline permeation was 0.044% (range 0.009-0.250%). In the presence of the detergent, permeation increased to 0.600% (range 0.007-2.260%) (P < 0.01). After oral intake of 750 mg of PS 15,000 (50 micrograms/ml; 15 ml), the 24-h urinary recovery was 0.013% (range 0.004-0.023%). Our study thus demonstrates a measurable baseline permeation of PS 15,000, an elevated permeation rate in the presence of an epithelium-damaging detergent molecule, and a negligible permeation by the oral route. These properties support the utility of PS 15,000 as a nasal airway permeation tracer. Its size further suggests that its permeation may reflect mucosal perviousness to many allergens.     

Evaluation of the effects of nasal decongestants with acoustic rhinometry

Acoustic rhinometry is a new method of evaluating the geometrical distributions of the cross-section and volume of the nasal cavity. Its characteristics are that of a nontraumatic procedure requiring minimal time for measurements. Eight males (27-39 years old) without nasal lesions were investigated with acoustic rhinometry before and after unilateral administrations of decongestants. Conventional nasal decongestants such as naphazolin nitrate 0.1% (Privina) and tetrahydrozoline hydrochloride 0.1%, as well as prednisolone 0.02% (Cor-tyzine), were used in solutions diluted 10 or 100 times. As to the method of decongestant application, we adopted the head tilt method, in the successive order of backward, lateral (toward the non-application side) tilt and backward. Each position was maintained for 30 seconds. Minimal cross sectional area of the nasal cavity, and nasal volume were evaluated with acoustic rhinometry. After the application of nasal drops, the minimal cross sectional area increased within 10 minutes, followed by a plateau level for one hour. With the application of nasal decongestants, an I-notch, corresponding to the nasal valve, was unchanged, whereas the C-notch, corresponding to the anterior and of the inferior turbinate, often shifted upwards. Thus, the minimal cross sectional area changed from an I-notch to a C-notch location. The volume of the nasal cavity increased within 10 minutes, and maintained a plateau level for one hour which was similar to that of the minimal cross sectional area. Changes in the ratio of the minimal cross sectional area were greater for less diluted solutions. Changes in the ratio of the nasal cavity were similar to those of the minimal cross sectional area.     

Acoustic rhinometry in the study of the acute nasal allergic response

Acoustic rhinometry is a recently developed method for the objective assessment of nasal patency. In this study, acoustic rhinometry was used to measure changes in nasal cavity dimensions in the immediate response to nasal allergen challenge in eight pollen-sensitive subjects. Acoustic rhinometric changes were compared with subjective symptoms, as well as histamine in nasal secretions, cytology of nasal mucosal scrapings, and changes in olfactory function. A significantly greater decrease in nasal airway caliber occurred following allergen challenge as compared to buffer diluent challenge in the same individuals (70% +/- 7% versus 22% +/- 5%). During an allergic response, a strong correlation was found between the minimum cross-sectional area and the volume of the nasal cavity measured by acoustic rhinometry (r = .9). However, no correlation was observed between nasal airway caliber and concomitant subjective congestion reported by the subjects. A modest decrease in olfactory function was seen following allergen challenge (3.1 +/- 1.4 fewer odors identified correctly out of 20; p = .08). However, the alterations of olfactory function did not correlate with changes in nasal patency. The results presented in this study demonstrate that acoustic rhinometry has great potential as a reproducible method for the objective assessment of nasal obstruction occurring in nasal allergen challenge studies.     

Spontaneous neoplasms of the nasal cavity in rats

The histomorphological features of two adenocarcinomas and two adenomas of the nasal cavity observed in two female Wistar rats and a male Sprague-Dawley rat are described. In one of the Wistar rats, a second tumour, classified as an adenoma, occurred in the posterior part of the nasal cavity.     

Training model for nasal packing

A model is described for practising packing of the nose with ribbon gauze in the treatment of epistaxis. The model was constructed from accurate casts of a cadaveric nasal cavity. The value of the model as a practical teaching aid is shown by a trial on a group of 15 accident and emergency (A&E) doctors. After training on the model, there was a significant improvement in the confidence of the doctors to pack a nose, the amount of gauze packed and the visual appearance of the pack. Use of the model should raise the generally poor standard of nasal packing by doctors working in A&E departments.     

Cytotoxic effects of islet cell surface antibodies

Antibodies against rat islet cells were produced by immunisation of rabbits with neonatal rat islet cells. In the presence of complement the rabbit anti-rat islet cell surface sera were strongly cytotoxic for both, neonatal rat islet cells and spleen lymphocytes as revealed by the high percentage of 51Cr release from these cells. However, after absorption with rat lymphocytes and rat liver powder the cytotoxicity of the islet cell antisera for rat lymphocytes was drastically reduced while the release of 51Cr from islet cells was only slightly influenced. These data indicate that islet cell specific antibodies were still present in the antisera after absorption. Native normal rabbit serum was also cytotoxic for neonatal rat islet cells and spleen lymphocytes. The release of 51Cr from islet cells and lymphocytes was vigorously reduced after absorption of the normal rabbit serum with lymphocytes and was paralleled by a similar decrease of insulin release from intact islets under conditions where the active insulin secretion was blocked pharmacologically. Intact islets prelabeled with 51Cr were also used as targets but this approach was less suitable for the detection of cytotoxic islet cell surface antibodies.     

Nasal cancer and nasal mucus-transport rates in woodworkers

Among 17 patients with adenocarcinoma of the nasal cavity, 12 had been heavily exposed to wood-dust inhalation, 10 as furniture makers, one as a turner, and one as a coach builder. Measurements of the nasal mucus-transport rate in 68 wood-dust workers demonstrated a significantly higher frequency of mucostasis than in a control group.     

Collapse of the nasal endotracheal tube in the nasal cavity

A 27-year-old female with maxillary maldevelopment was admitted for mandibular sagittal splitting osteotomy with mandibular progeny. General anesthesia was induced with 100 mg of propofol and 8 mg of vecuronium. When a soft and preformed 7.0 mm North-Polar-nasotracheal tube (Portex) was inserted into the nasopharynx through the left nasal cavity, it was very difficult to advance beyond the choana. After nasotracheal intubation, the buking became harder than before when she had been ventilated with a face mask. The peak airway pressure had reached higher than 50 cmH2O with ventilation of 500 ml tidal volume. Bronchoscopy revealed that the fiberscope (3.5 mm O.D.) could not go through the choanal stenosis, because it was too narrow. Therefore, she had to be intubated by a spiral tube, 6.0 mm I.D., through the other nasal cavity with assistance of bronchoscopy, instead of the North-Polar-tube. So, we have to pay attention to the possibility of compression and collapse of a soft nasotracheal tube in the nose of the patient with choanal stenosis due to maxillary maldevelopment.     

Absorption, pharmacokinetics and metabolism of 14C-sumatriptan following intranasal administration to the rat

1. Studies have been carried out to investigate the absorption of sumatriptan after intranasal administration to rats. The pharmacokinetics, metabolism and excretion of 14C-sumatriptan were compared following intranasal and intravenous dosing to male and female albino rats using an aqueous buffered formulation at pH 5.5. 2. Following intravenous administration sumatriptan was eliminated from plasma with a half-life of about 1.1 h. After intranasal administration there was rapid absorption of part of the dose and two peak plasma concentrations were observed, initially at 0.5 and then at 1.5-2 h. The elimination half-life after the second peak was estimated as being about 4 h. 3. Radioactivity was largely excreted in urine (up to 89% of dose in 168 h) after both intravenous and intranasal administration, with a faster rate of excretion after intravenous dosage (73% males, 64% females within 6 h) than after intranasal dosage (37% males, 40% females within 6 h). 4. 14C-sumatriptan was the major component in urine and in extracts of faeces after both intravenous and intranasal administration. The major metabolite excreted in urine and faeces was GR49336, the indole acetic acid analogue. 5. The results of this in vivo rat study suggest that absorption of the dose via the nasal mucosa is incomplete after intranasal administration and that there is a secondary absorption phase probably reflecting oral absorption of part of the dose. The bioavailability is estimated as about 30%, for the period 0-6 h.     

The effect of unilateral nasal patency on the contralateral side

This investigation was designed to verify the possible feed-back mechanism which works to compensate for changes in the nasal volume of one side by the other side. Acoustic rhinometry, with which nasal volume is easily evaluated, was used in this investigation. Acoustic rhinometry was performed at 4 points in time (immediately after, and three, six and nine minutes after, the setting of experimental conditions). This investigation was composed of two studies. In the first study, ten healthy subjects (nine males and one female, 26-49 years of age, mean age 30 years) were evaluated to estimate the effect of decreased unilateral nasal patency upon the other side. In this study, one nasal cavity was occluded with an acryle plug, and the nasal volume of the other side was evaluated by acoustic rhinometry before and after the occlusion. In the second study eight healthy subjects (five males and three females, 24-34 years of age, mean age 29 years) were evaluated to estimate the effect of increased unilateral nasal patency upon the other side. This study covered a period of three days. A small piece of cotton soaked in a vasoconstrictor solution (1/1000 adrenalin or 0.05% naphazolin nitrate) was put in one nasal cavity (the right on the first day, the left on the second day) and the other side was evaluated before and after administration of the solution. On the third day of the control study, a similar piece of cotton soaked in physiological saline solution was put in one nasal cavity, and the other side was evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bovine nasal granuloma: a review

The literature on granulomatous nasal diseases of cattle is reviewed, with emphasis on nasal granuloma, a disease of unknown cause which is enzootic in Australian dairy cattle. It is concluded that on available evidence the disease is most probably a form of allergic rhinitis.     

Cobalt 60 radiotherapy for treatment of squamous cell carcinoma of the nasal cavity and paranasal sinuses in three horses

Three adult horses underwent aggressive treatment of squamous cell carcinoma of the nasal cavity and paranasal sinuses, using course-fractionated cobalt 60 radiotherapy. Squamous cell carcinoma of the nasal cavity and paranasal sinuses is not commonly diagnosed in horses. Historically, horses with this type of neoplasm have not been treated or have undergone some form of surgery. The prognosis for long-term survival or cure has been poor. Long-term results of cobalt 60 radiotherapy were good to excellent and exceeded those usually reported for horses treated surgically. On the basis of these results, use of radiotherapy for these neoplasms is recommended.     

Treatment of planocellular carcinoma of the nasal vestibule

In the ICD-9 system, carcinomas of the nasal vestibule are classified together with carcinomas in the nasal cavity. As a rule, however, they are squamous cell carcinomas derived from the skin, and thus prognosis is better than in the case of squamous cell carcinomas derived from the mucosa of the nasal cavity. The article highlights essential features of brachytherapy. The authors present a critical assessment of the criteria for staging, and describe a specific patient material. Based on clinical experience and theoretical considerations, brachytherapy alone is recommended for T1-3 N0 tumours. In the case of T4 tumours external radiation therapy and brachytherapy combined is recommended for the primary tumour, with prophylactical irradiation towards regional lymph nodes.     

A new pneumatic nasal tamponade (author's transl)

In order to control severe bleeding in the nose and nasopharynx, a pneumatic nasal tamponade has been devised. The tube is available in three sizes, and can be easily introduced into the nasal cavity to sufficiently block bleeding areas.     

Actinomycosis in otorhinolaryngology. Apropos of a case with localization in the nasal cavity

The authors report an atypical case of actionomycosis implanted in the nasal cavity and occurring twenty years after septum surgery. Treatment by penicillin and surgical excision gave a good result. Cervicofacial actinomycosis is caused by actinomyctes which usually lives as a saprophyte in the oral cavity. A trauma is often found in the previous history. Diagnosis with tumors and abscess may be difficult. The histopathological examination shows typical aspects of the granuloma (gram+ and Grocott+) and the bacteriological isolation of the germ is difficult to obtain. Penicillin associated with surgical excision is the best therapy, but high doses must be used for a long time. The literature is reviewed without finding such a case.