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[Corticotropic action of a new, synthetic analogue of ACTH (ACTH1-17) in man after intravenous, intramuscular and intranasal administration (author's transl)].

Ala1-lys17-ACTH(1-17)-4-amino-n-butylamide (ACTH1-17), a synthetic analogue of ACTH with shortened amino acid sequence exerts a corticotropic action of at least 8 hours duration in healthy male subjects after either intravenous or intramuscular administration. After intranasal administration of the compound an increased production of cortisol was observed only for three hours. The prolonged action of this new analogue of ACTH following intramuscular administration suggests that it may be of value for therapeutic purposes.

Administration, Intranasal

Plasma gonadotropin and gonadotropin-releasing hormone levels after intranasal administration of gonadotropin releasing hormone.

Intranasal administration of gonadotropin hormone (GnRH) in doses ranging from 2-4 mg produced a consistently prolonged LH response in patients with secondary amenorrhea. In 4 cases, a delayed secondary rise occurred. A similarly prolonged FSH response was observed in the majority of patients. Six hours after intranasal GnRH, FSH and LH values were well above basal levels and were higher than those observed at a similar interval after intravenous GnRH. Plasma GnRH levels after intranasal administration failed to achieve the high peaks found after the intravenous route but maintained elevated levels for at least an hour and often longer. Despite the much lower plasma GnRH levels, intranasal GnRH produced a sustained effect on LH and FSH secretion, greater than GnRH given by the intravenous route.

Administration, Intranasal

Luteolytic effect of intranasal administration of [D-Ser(TBU)6,DES-Gly-NH2(10)]-luteinizing hormone-releasing hormone ethylamide in normal women.

Intranasal administration of two doses of potent agonist of luteinizing hormone (LH)-releasing hormone (LHRH), [D-Ser(TBU)6,des-Gly-NH2(10)]LHRH ethylamide (500 micrograms), a 8 A.M. and 5 P.M. on 1 day between day 4 and 9 following the LH peak in six normal women during two consecutive menstrual cycles shortened the luteal phase from 13.6 +/- 0.3 days to 10.9 +/- 0.3 days (mean shortening, 2.7 days; range, 0.5 to 4.5 days) and reduced plasma progesterone levels to 61.3% +/- 9.2% of control. Hormone changes were followed by daily measurements of plasma LH, follicle-stimulating hormone, 17 beta-estradiol, and progesterone during two pretreatment cycles, two treatment cycles, and two post-treatment cycles. No side effect was observed, and apparently normal cycles occurred immediately after treatment. The present data indicate that the intranasal administration of a potent LHRH agonistic analog can induce luteolysis and control time of occurrence of menses in normal women. This finding opens the possibility of a new and physiologic approach to fertility control.

Administration, Intranasal

Prolonged elevation of luteinizing hormone (LH) after intranasal administration of an analog of LH-releasing hormone.

[D-Leu-6,desGly-NH2-10]-LH-RH-ethylamide, an analog of luteinizing hormone-releasing hormone (LH-RH), was administered by intranasal spray or tube to 18 healthy men. A significant release of LH occurred within 15 minutes and was sustained for as long as 12 hours in what appeared to be a diphasic response. Both the spray and rhinyl tube were shown to be effective methods for releasing LH by intranasal administration of the LH-RH analog.

Administration, Intranasal

Efficacy of intravaginal and intranasal administration of micronized estradiol-17beta.

Absorption of micronized 17beta-estradiol (E2), after intravaginal administration of 1 mg dose, suspended in saline, is extremely rapid and sustained. A mean peak increment of circulating E2 concentrations of more than 110 times the basal level is achieved at 2 h and remains elevated more than 6 times the basal level even at 24 h. Increments in estrone (E1) are smaller and slower than those of E2 with a mean peak concentration of less than 10% of E2 and remain 3 times the basal level at 24 h. With 0.5 mg dose, the incremental changes in E2 and E1 as well as the degree of gonadotropin suppression are essentially the same. In contrast, intranasal administration of E2 of 1 mg dose induces a rapid but short-lasting increase in both serum E2 and E1 levels. The mean increments of E1 exhibited a higher and sustained elevation with a rise in mean E1/E2 ratio well above unity beginning 1 hr after intranasal application. These findings indicate intravaginal but not intranasal routes of E2 absorption are quantitatively much greater and circumvent the local conversion of E2 to E1 observed after oral administration of E2, and thus represent a practical and highly effective means of delivering E2 into the circulation.

Administration, Intranasal

Hyposensitization of patients with allergic rhinitis by intranasal administration of chemically modified grass pollen allergen. A pilot study.

In a pilot study, five adult patients with allergic rhinitis due to grass pollen underwent local intranasal hyposensitization with a chemically modified grass pollen extract--a so-called allergoid. Local hyposensitization during a pre-seasonal period resulted in an increased serum level of timothy-specific IgE antibodies in all patients, indicating that the allergoid had immunogenic properties. In four of the patients the clinical effect during the grass pollen season was judged satisfactory. Pre- and post-seasonal provocation test in these four patients also showed a reduction of the nasal sensitivity during this period. All patients tolerated the treatment well without any marked side effects. These promising preliminary results motivate further investigation into this form of therapy.

Administration, Intranasal

Urinary excretion of immunologically reactive metabolite(s) after intranasal administration of cocaine, as followed by enzyme immunoassay.

Using the enzyme immunoassay technique (EMIT), we determined the time course of urinary excretion of benzoylecgonine in 16 surgical patients and three volunteers who received intranasal cocaine. After doses varying from 13 to 130 mg, the test for benzoylecgonine was positive in 1 to 4 h, peaked at about 10 to 12 h, remained positive for 18 to 27 h, and became negative after about 17 h. This information should be considered by drug dependency treatment programs in which the EMIT procedure is used to screen urines for cocaine use.

Administration, Intranasal

Evaluation of transduction properties and vaccine efficacy of a simian adenovirus type 25-based vector.

Although human adenovirus serotype 5 (Ad5) is widely used as a vaccine vector for infectious diseases due to its high transduction efficiency, pre-existing immunity to Ad5 in many people reduces vaccine efficacy. To address this limitation, simian Ad vectors, such as ChAdOx1 and ChAdOx2, have been explored as alternative vaccine platforms. ChAdOx2 is based on simian Ad25 (SAd25), but the fundamental characteristics of gene transduction by SAd25-based vectors have not been fully elucidated. This study aimed to characterize the gene transduction efficiency, tissue distribution, and immunogenicity of an SAd25-based vector in comparison with those of the Ad5 vector following various routes of administration. Compared with intravenous administration of the Ad5 vector, intravenous administration of the SAd25 vector showed distinct biodistribution patterns, including reduced liver accumulation and predominant expression in the lung. Transduction by the SAd25 vector was not inhibited by human serum, whereas transduction by the Ad5 vector was inhibited, indicating that the SAd25 vector, but not the Ad5 vector, can evade pre-existing Ad immunity. Although intramuscular administration of the SAd25 vector induced lower transgene product-specific antibody production than intramuscular administration of the Ad5 vector, gene expression and Ad genome distribution mediated by the SAd25 vector, but not the Ad5 vector, were localized only to the muscle at the administration site. Intranasal administration of the SAd25 vector induced an antigen-specific antibody response in serum more rapidly than intranasal administration of the Ad5 vector. The SAd25 vector induced antigen-specific antibody production in bronchoalveolar lavage fluid (BALF) that was comparable to that induced by the Ad5 vector. These findings provide essential insights into the biological characteristics of the SAd25 vector, supporting its potential as a safe and effective vaccine vector.

Animals

[The treatment of patients with diabetes insipidus by a synthetic analogue of vasopressin, DDAVP (author's transl)].

The effects of a synthetic analogue of vasopressin, DDAVP (1-deamino-8-D-arginine vasopressin) were investigated in 98 patients with cranial diabetes insipidus. In all patients, intranasal administration of DDAVP one to three times daily, usually twice daily, was found to be satisfactory in the control of diabetes insipidus. Thus, by DDAVP administration, daily urinary volume changed from 3520 +/- 2150 ml to 1620 +/- 830 ml (mean +/- SD), and urinary osmolarity changed from 126 +/- 75 mOsm/kgH2O to 446 +/- 194 mOsm/kgH2O (mean +/- SD). A daily dose of DDAVP ranged from 2.0 to 20 microgram in children (average dose 12.8 microgram), while 10 to 20 microgram of DDAVP was usually required in adult patients (average dose 14.2 microgram). No serious side effects have been observed. It is concluded that DDAVP is safe and effective in the treatment of cranial diabetes insipidus.

Administration, Intranasal

Clinical evaluation of intranasal topical flunisolide therapy in allergic rhinitis.

A double-blind, vehicle control, parallel clinical trial evaluated the effectiveness and safety of the local application of flunisolide, a potent new topical steroid, in the treatment of ragweed hay fever. Fifty patients with well-defined, poorly controlled ragweed allergy were studied during the 1974 ragweed season. Analysis of the data showed that the active drug group had a significant decrease in individual symptoms of sneezing, nasal stuffiness, and nasal secretions, compared with the placebo group. Antihistamine usage was statistically decreased in the active drug over placebo group. There was no evidence of adrenal suppression. This study indicates that intranasal administration of flunisolide in adult patients is both efficacious and safe in the treatment of seasonal allergic rhinitis.

Administration, Intranasal

Assessment of pituitary response to nasal application of synthetic gonadotropin-releasing hormone in men.

An attempt has been made to assess the pituitary response to the nasal application of synthetic gonadotropin-releasing hormone (GnRH) in three oligospermic and two azoospermic men. Intranasal administration of 3 mg of GnRH in aqueous or natural plant gum solution produced a pituitary response pattern similar to that produced by the intramuscular injection of 100 microng, with respect to plasma concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). No technical difficulties or side effects were observed. GnRH in a nasal drop preparation seems to be effective in releasing LH and FSH in men. These findings may have a practical application in those cases where long-term therapy with the hormone is indicated.

Administration, Intranasal

Clinical trials of immunization with the Towne 125 strain of human cytomegalovirus.

The Towne 125 strain of human cytomegalovirus (CMV), adapted to growth in human diploid cell strain WI-38 and propagated in this cell line for 129 consecutive passages, was administered to male volunteers with or without preexisting antibodies to CMV. Infection was not achieved by intranasal administration. In contrast, subcutaneous inoculation of virus induced seroconversion in all seronegative volunteers and a booster antibody response in some previously seropositive individuals. Transient local reactions occured at the site of inoculation of the virus, but systemic symptoms and signs of disease were notably absent.

Administration, Intranasal

Neutralizing influenza antibodies, IgA and total protein in the nasopharyngeal secretions of subjects vaccinated by nasal route with the inactivated influenza vaccine prepared in the "Stefan S. Nicolau" Institute of Virology.

Intranasal administration of two doses of the inactivated influenza vaccine prepared in the "Stefan S. Nicolau" Institute of Virology was followed by rises in the level of neutralizing secretory influenza antibodies in 82% of the cases. The concomitant study of secretory antibody, IgA and total protein levels, as well as of the serum HAI influenza antibodies demonstrated that their evolution was parallel only in 23% of the vaccinees. The percentage of secretory antibody conversion was similar to the rate of protection conferred by the vaccine.

Administration, Intranasal

Immunity studies in calves vaccinated with a multivalent live respiratory vaccine composed of I.B.R., parainfluenza 3 and bovine adenovirus type 3.

The persistence of systemic and local antibodies was studied after two intranasal administrations of the vaccine, six weeks apart. Systemic antibodies to I.B.R. and adenovirus 3 evoked by the vaccine were still present 21 weeks following the second dose of the vaccine. Inconslusive results were obtained regarding the persistence of systemic and local PI-3 antibodies because of an intercurrent natureal PI-3 infection occurring during the observation period. Local antibodies to adenovirus type 3 were found in a high percentage of vaccinated animals 21 weeks after the second dose of the vaccine, whereas local antibodies to I.B.R. remained detectable in 50% of the animals eight weeks after thesecond dose. The results of a challenge study 21 weeks after revaccination show that the presence of local and systemic antibodies prevent the multiplication of PI-3 and BAV-3 in the upper respiratory tract. Protection against I.B.R. was achieved in the absence of detectable local antibodies.

Adenoviridae