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Results for “Administration, Intranasal”

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PubMed1992

High- and low-challenge exposure doses used to compare intranasal and intramuscular administration of pseudorabies virus vaccine in passively immune pigs.

We compared 3 modified-live pseudorabies virus (PRV) vaccine strains, administered by the intranasal (IN) or IM routes to 4- to 6-week-old pigs, to determine the effect of high- and low-challenge doses in these vaccinated pigs. At the time of vaccination, all pigs had passively acquired antibodies to PRV. Four experiments were conducted. Four weeks after vaccination, pigs were challenge-exposed IN with virulent virus strain Iowa S62. In experiments 1 and 2, a high challenge exposure dose (10(5.3) TCID50) was used, whereas in experiments 3 and 4, a lower challenge exposure dose (10(2.8) TCID50) was used. This low dose was believed to better simulate field conditions. After challenge exposure, pigs were evaluated for clinical signs of disease, weight gain, serologic response, and viral shedding. When vaccinated pigs were challenge-exposed with a high dose of PRV, the duration of viral shedding was significantly (P less than 0.05) lower, and body weight gain was greater in vaccinated pigs, compared with nonvaccinated challenge-exposed pigs. Pigs vaccinated IN shed PRV for fewer days than pigs vaccinated IM, but this difference was not significant. When vaccinated pigs were challenge-exposed with a low dose, significantly (P less than 0.05) fewer pigs vaccinated IN (51%) shed PRV, compared with pigs vaccinated IM (77%), or nonvaccinated pigs (94%). Additionally, the duration of viral shedding was significantly (P less than 0.05) shorter in pigs vaccinated IN, compared with pigs vaccinated IM or nonvaccinated pigs. The high challenge exposure dose of PRV may have overwhelmed the local immune response and diminished the advantages of the IN route of vaccination.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

PubMed2001

Delivery of neurotrophic factors to the central nervous system: pharmacokinetic considerations.

Neurotrophic factors are proteins with considerable potential in the treatment of central nervous system (CNS) diseases and traumatic injuries. However, a significant challenge to their clinical use is the difficulty associated with delivering these proteins to the CNS. Neurotrophic factors are hydrophilic, typically basic, monomeric or dimeric proteins, mostly in the size range of 5 to 30 kDa. Neurotrophic factors potently support the development, growth and survival of neurons, eliciting biological effects at concentrations in the nanomolar to femtomolar range. They are not orally bioavailable and the blood-brain and blood-cerebrospinal fluid barriers severely limit their ability to enter into and act on sites in the CNS following parenteral systemic routes of administration. Most neurotrophic factors have short in vivo half-lives and poor pharmacokinetic profiles. Their access to the CNS is restricted by rapid enzymatic inactivation, multiple clearance processes, potential immunogenicity and sequestration by binding proteins and other components of the blood and peripheral tissues. The development of targeted drug delivery strategies for neurotrophic factors will probably determine their clinical effectiveness for CNS conditions. Achieving significant CNS target site concentrations while limiting systemic exposure and distribution to peripheral sites of action will lessen unwanted pleiotropic effects and toxicity. Local introduction of neurotrophic factors into the CNS intraparenchymally by direct injection/infusion or by implantation of delivery vectors such as polymer matrices or genetically modified cells yields the highest degree of targeting, but is limited by diffusion restrictions and invasiveness. Delivery of neurotrophic factors into the cerebrospinal fluid (CSF) following intracerebroventricular or intrathecal administration is less invasive and allows access to a much wider area of the CNS through CSF circulation pathways. However, diffusional and cellular barriers to penetration into surrounding CNS tissue and significant clearance of CSF into the venous and lymphatic circulation are also limiting. Unconventional delivery strategies such as intranasal administration may offer some degree of CNS targeting with minimal invasiveness. This review presents a summary of the neurotrophic factors and their indications for CNS disorders, their physicochemical characteristics and the different approaches that have been attempted or suggested for their delivery to the CNS. Future directions for further research such as the potential for CNS disease treatment utilising combinations of neurotrophic factors, displacement strategies, small molecule mimetics, chimaeric molecules and gene therapy are also discussed.

Animals↗

PubMed1999

Regeneration of olfactory receptor neurons following chemical lesion: time course and enhancement with growth factor administration.

Although it has been known for over 50 years that olfactory receptor neuron (ORN) neurogenesis and subsequent reinnervation of the olfactory bulb (OB) occurs following ORN injury, the precise intrinsic and extrinsic factors that regulate this dynamic process have not yet been fully identified. In the first of two experiments, we characterized the time course of anatomical recovery following zinc sulfate (ZnSO(4)) lesion of ORNs in adult male Sprague-Dawley rats. ZnSO(4) produced a near complete deafferentation of OB within 3 days following intranasal administration. A time-dependent increase in ORN reinnervation of OB was observed following 10, 20, and 30 day recovery intervals. Given the evidence that bFGF, EGF, and TGF-alpha have mitogenic effects on ORNs in vitro, a second experiment examined the extent to which these growth factors (GFs) might enhance ORN regeneration and subsequent reinnervation of OB in vivo. Rats received intranasal infusions of ZnSO(4) on day 0, followed by subcutaneous injections of either bFGF (5, 10, or 50 microgram/kg), EGF (5, 10, or 50 microgram/kg), or TGF-alpha (5 or 10 microgram/kg) on days 3-6. Horseradish peroxidase (HRP) histochemistry of OB following a 10-day recovery period revealed a dose-related enhancement in reinnervation of OB for each of the three growth factors examined, with the greatest enhancement produced by TGF-alpha. These data suggest that GFs may regulate ORN mitogenesis in vivo in a way similar to that which has been characterized in vitro.

Animals↗

PubMed1973

In vivo studies with collagenase from Pseudomonas aeruginosa.

An extracellular protease from Pseudomonas aeruginosa having collagenase activity was assayed in vivo. The lethality of the enzyme for white female mice was determined by use of intravenous, intraperitoneal, intranasal, and subcutaneous routes, respectively. The collagenase exhibited the following 72-hr mean lethal dose values: intranasally, 55 collagenase units; intraperitoneally, 148 collagenase units; and intravenously, 288 collagenase units. In the concentrations tested, no lethality was obtained when the subcutaneous route was employed. Gross and microscopic studies revealed that the collagenase was capable of eliciting a variety of tissue responses in mice depending upon its route of administration. Intranasal instillation resulted in confluent pulmonary hemorrhage, whereas intraperitoneal injections resulted in severe abdominal hemorrhage with foci on the intestinal serosa. Intravenous injections elicited abdominal hemorrhage and petechial hemorrhage with focal necrosis of the lungs, whereas subcutaneous injections resulted in necrotic, ulcerating lesions.

Bacterial Proteins↗

PubMed2005

No defect in T-cell priming, secondary response, or tolerance induction in response to inhaled antigens in Fms-like tyrosine kinase 3 ligand-deficient mice.

BACKGROUND: Respiratory tract dendritic cells (DCs) are crucial for the regulation of immune responses to inhaled antigens. However, the precise function of the multiple DC subsets present in the lungs and the lung-draining lymph nodes is unknown. Fms-like tyrosine kinase 3 ligand (FLT3L) is a hematopoietic growth factor that drives the development of multiple subsets of DCs in the lymphoid organs. OBJECTIVE: We sought to study the contribution of DC subsets in the regulation of the balance between tolerance and immunity against respiratory antigens by using FLT3L knockout mice. METHODS: Phenotypic analysis of DC subsets in the airways and lungs of FLT3L knockout mice was performed. By using various experimental models, the role of FLT3L-dependent DCs in the priming of naive T cells, the presentation of inhaled antigen to previously primed T H 2 cells, and intranasal tolerance induction was addressed. RESULTS: FLT3L knockout mice display a 90% reduction in lung parenchyma DCs but a normal number of airway DCs and blood monocytes. FLT3L knockout mice had a normal induction of eosinophilic inflammation in response to intranasal administration of allergen. FLT3L-dependent DCs were not required for the presentation of inhaled antigen to previously primed T H 2 cells, and normal induction of T-cell tolerance in response to inhaled antigen was observed in FLT3L knockout mice. CONCLUSION: Airway DC development is independent of FLT3L. FLT3L-dependent DCs are not required for the development and maintenance of airway inflammation or for the induction of intranasal tolerance. Our results point to airway DCs as the major regulators of the balance between tolerance and immunity to inhaled antigens.

Administration, Inhalation↗

PubMedDate not supplied

[The role of hyaluronidase in the occurrence of a generalized pneumococcal infection].

The hyaluronidase activity of pneumococcal strains isolated from 39 patients with purulent meningitis, 26 patients with acute internal otitis and 130 healthy carriers was studied. All strains isolated from patients with purulent meningitis and meningoencephalitis and 84.6% of strains isolated in cases of otitis were found to have hyaluronidase, while in healthy children hyaluronidase-synthesizing strains were detected only in 11.5% of cases. Hyaluronidase titers in pneumococcal strains isolated from patients with meningitis and meningoencephalitis were significantly higher than in strains causing purulent otitis. At the same time strains with high hyaluronidase titers were also isolated from 7% of healthy carriers. Noncapsular pneumococcal strains had no hyaluronidase. The average value of the reverse correlation between hyaluronidase activity and the virulence of strains for mice was established. Hyaluronidase activity did not correlate with different serotypes of pneumococcal strains. The intranasal administration of hyaluronidase in high titers (> or = 1:8) to mice and rats led to the penetration of the infective agent through the hematoencephalic barrier of the animals and to their death from generalized pneumococcal infection. The role of hyaluronidase as the invasiveness factor of pneumococci was confirmed in experiments on the intranasal infection of mice with low active strains mixed with the preparation of exogenous hyaluronidase.

Acute Disease↗

PubMed1996

Mucosal immunization with a measles virus CTL epitope encapsulated in biodegradable PLG microparticles.

The immunogenicity of a cytotoxic T cell epitope (CTL) representing residues 52-60 from measles virus (MV) nucleoprotein, encapsulated in poly(lactide-co-glycolide) (PLG) microparticles was evaluated after mucosal immunization. After intranasal administration of the encapsulated CTL epitope linked at the carboxyl terminus of two copies of a T-helper epitope (TT-NP6), peptide-specific and MV-specific CTL responses were detected in splenocytes. However, these responses were lower than the responses observed when the TT-NP6 peptide was administered intranasally in saline or using CTB as an adjuvant. Intranasal coadministration of the encapsulated TT-NP6 peptide with CTB did not result in any significant potentiation of the CTL responses. The effectiveness of biodegradable PLG microparticles for mucosal delivery of CTL epitopes, combined with their excellent tissue compatibility and biodegradability suggests that they represent a valuable delivery system for synthetic immunogens. However, further work is needed to define the requirements for effective absorption by the nasal epithelium.

Animals↗

PubMed2000

Lung overexpression of the vascular endothelial growth factor gene induces pulmonary edema.

We hypothesized that the angiogenic mediator, vascular endothelial growth factor (VEGF), known to be expressed in the lung and to be capable of inducing local edema in skin, might evoke the development of lung edema if expressed in excess amounts. To test this hypothesis, we developed an in vivo model of VEGF overexpression in the lung on the basis of delivery to the respiratory epithelium of the VEGF165 complementary DNA by an E1(-) adenovirus vector (AdVEGF165). Administration of AdVEGF165 by the intratracheal route (10(9) plaque-forming units [pfu]) to C57Bl/6 mice showed increased expression of VEGF messenger RNA in lung tissue by Northern analysis. Overexpression of VEGF protein in the lung at Days 1 to 10 was confirmed by enzyme-linked immunosorbent assay. Intratracheal administration of AdVEGF165 resulted in a dose-dependent increase in lung wet/dry weight ratios over time, lung histology showed widespread intra- alveolar edema, and pulmonary capillary permeability was significantly increased as quantified by the Evans blue dye assay and [(131)I]albumin permeability. To confirm the specificity of these observations, mice were pretreated with intranasal administration of an adenovirus vector expressing a truncated soluble form of the VEGF receptor flt-1 (Adsflt). Adsflt (10(9) pfu) pretreatment completely abrogated the increased lung wet/dry weight ratio caused by AdVEGF165 administration, whereas an identical adenovirus vector with an irrelevant transgene had no effect upon subsequent AdVEGF165-induced pulmonary edema. Together, these data suggest that overexpression of VEGF in the lung may be one mechanism of increased pulmonary vascular permeability in the early stages of acute lung injury.

Administration, Inhalation↗

PubMed2002

Immune responses in mice to intranasal and intracutaneous administration of a DNA vaccine encoding Helicobacter pylori-catalase.

We previously reported that the intracutaneous injection of DNA vaccines encoding Helicobacter pylori heat shock proteins elicited specific immune responses, and led to reduced infection in mice. In this study, we constructed DNA vaccine encoding H. pylori-catalase (pcDNA3.1-kat) and investigated the immune responses to intranasal and intracutaneous administration of pcDNA3.1-kat. C57/BL6 mice were immunized intracutaneously with 10 microg of pcDNA3.1-kat or intranasally with 50 microg of pcDNA3.1-kat. Catalase-specific IgG antibody was detected in the sera of intranasal and intracutaneous immunized mice. Both intranasal and intracutaneous immunized mice were significantly protected from colonization by H. pylori and had significantly reduced degrees of gastritis. These results demonstrate that DNA vaccine encoding H. pylori-catalase can induce an immune response against H. pylori, and that intranasal immunization works as well as intracutaneous immunization.

Administration, Intranasal↗

PubMed1998

In vivo adulteration: excess fluid ingestion causes false-negative marijuana and cocaine urine test results.

Drug users can be highly motivated to obtain negative results on urine drug tests and may attempt to subvert the process by in vivo adulteration. The use of herbal products for "flushing" and "detoxification" is frequently advertised as an effective means of passing drug tests. Accordingly, a study was designed to determine the effects of ingestion of two herbal products, Naturally Klean Herbal Tea and Golden Seal root, and a diuretic medication, hydrochlorothiazide. The herbal tea was prepared in 1 gal of water as specified by the manufacturer. All other products were consumed with 1 gal of water. Two control conditions in which the subject consumed only water (1 gal; 12 oz) were included. The 1-gal liquid treatments were divided into 4-qt aliquots, and 1-qt was consumed each hour for 4 h. All treatments were begun approximately 22 h after smoking of a marijuana cigarette (3.58% THC) and 22 h after intranasal administration of cocaine hydrochloride. Following all treatments with excess fluid, creatinine and specific gravity dropped in 1.5-2.0 h to levels indicative of diluted specimens (<20 mg/dL creatinine, <1.003 specific gravity). Marijuana and cocaine metabolite concentrations by immunoassay (EMIT and TDx) also dropped rapidly, and the results frequently switched from positive to negative. By the time subjects had consumed 2 qt of any fluid, they were generally producing false-negative results. For example, ingestion of excess water produced dilute specimens (<20 mg/dL creatinine; <1.003 specific gravity) in an average time plus or minus the standard error of the mean of 1.47 +/- 0.17 h (N = 5) and 1.45 +/- 0.2 h (N = 5) following smoked marijuana and intranasal cocaine, respectively. In comparison, ingestion of Klean Tea produced dilute specimens in 1.36 +/- 0.07 h (N = 4) and 1.39 +/- 0.11 h (N = 4) following marijuana and cocaine administration. Recovery of urine test measures to pre-treatment levels occurred over a period of 8-10 h. Average detection times for marijuana metabolite appeared to be slightly shorter following ingestion of 1 gal of fluids compared with ingestion of 12 oz of water as a result of the time of testing being near the end of the cannabinoid metabolite excretion phase. Consequently, negative cannabinoid results induced by fluid ingestion rarely returned to positive after excess water was eliminated. In contrast, negative cocaine results reverted to positive quickly after the dilution effects disappeared. It was concluded that excess water ingestion can produce false-negative test results, but the claims of herbal products to be an aid in passing a urine test appear to be unfounded.

Adult↗

PubMed1978

Lung response to congenitally athymic (nude), heterozygous, and Swiss Webster mice to aerogenic and intranasal infection by Nocardia asteroides.

Congenitally athymic (nude, Nu/Nu), heterozygous (Nu/+), and Swiss Webster mice were exposed to virulent Nocardia asteroides GUH-2 inhaled from aerosols or administered intranasally. Clearance of the bacteria from the lungs was determined at 6 h and 1, 2, 3 and 7 days after infection. N. asteroides aspirated into the lungs from intranasal administration were killed less rapidly and induced more severe pulmonary infections than did comparable numbers of organisms inhaled from aerosols. Bacterial clearance and histological data indicated that nude mice were significantly more susceptible to nocardial infection than were heterozygous littermates or Swiss Webster mice. From these data we conclude that: (i) pulmonary defenses cope less well with intranasally administered N. asteroides than with aerosolized organisms, (ii) alveolar macrophages alone appear not to be an efficient barrier to nocardial infections, and (iii) T cells are important to pulmonary clearance and prevention of dissemination of N. asteroides from the lung.

Animals↗

PubMedDate not supplied

[Maprotiline versus fluvoxamine: comparison of their effects on the hypothalamo-hypophyseal-thyroid axis].

The TRH test has been used in psychiatry these last 20 years. One of the most promising results is that concerning the possibility to use it to identify the best moment to stop a treatment after clinical recovery of the depressive episode. For that it is necessary to demonstrate an absence of intrinsic action of antidepressants on the HPT axis physiology. This overt, randomized study has compared the actions on T3, T4, basal TSH and its response to the TRH test after 75 mg/day of maprotiline and 100 mg/day of fluvoxamine, both administrated in depressed patients during 28 days. Forty patients (20 men and 20 women) were studied, 20 patients per treatment. The inclusion criteria were those of DSM III-R for major depression and dysthymia as well a minimum score of 25 at MADRS scale. Blood samples for T3, T4 and basal TSH dosages were made before TRH intranasal administration (2 mg) at days 1 and 28 of the treatment. We haven't observed any difference before treatment between the 2 groups for clinical and biological studied parameters. After treatment both antidepressants produced equivalent improvement of depression evaluated by MADRS (fluvoxamine:dMADRS = 16.95 +/- 7.11; maprotiline: dMADRS = 17.10 +/- 6.84. t = 0.07, NS). T3 and T4 variations between the beginning and the end of the study weren't also significantly different between the 2 groups. Basal TSH was increased in the maprotiline group but decreased in the fluvoxamine group resulting in a significant difference (fluvoxamine: dTSH = 0.31 +/- 0.76 mUI/l. Maprotiline : dTSH = -0.23 +/- 0.66 mUI/l. t = 2.40, p < 0.02). The TSH response to TRH was decreased in the fluvoxamine group (ddTSH = 0.24 +/- 6.65 mUI/l. dAUC = 103.98 +/- 596.84 mUI/l) while it was increased in the maprotiline group (ddTSH = -3.59 +/- 5.88 mUI/l. dAUC = -355.80 +/- 505.67 mUI.min/l). The difference between the 2 treatments was not significant when evaluated by ddTSH (t = 1.53, NS) but it became significant if evaluated by dAUC (t = 2.63, p < 0.01). As we could demonstrate an absence of influence of the clinical evolution between both groups in the hormonal variations observed, we concluded to a intrinsic difference action on HPT axis between fluvoxamine and maprotiline. This difference could be linked to the different aminergic action of these 2 antidepressants.

Adult↗

PubMed2001

Derivation and characterization of a live attenuated equine influenza vaccine virus.

OBJECTIVE: To develop and characterize a cold-adapted live attenuated equine-2 influenza virus effective as an intranasal vaccine. ANIMALS: 8 ponies approximately 18 months of age. PROCEDURES: A wild-type equine-2 virus, A/Equine/Kentucky/1/91 (H3N8), was serially passaged in embryonated chicken eggs at temperatures gradually reduced in a stepwise manner from 34 C to 30 C to 28 C to 26 C. At different passages, infected allantoic fluids were tested for the ability of progeny virus to replicate in Madin-Darby canine kidney (MDCK) cells at 34 C and 39.5 C. Virus clones that replicated at 26 C in eggs and at 34 C in MDCK cells, but not at 39.5 C in MDCK cells, were tested for stability of the cold-adapted, temperature-sensitive (ts), and protein synthesis phenotypes. A stable clone, P821, was evaluated for safety, ability to replicate, and immunogenicity after intranasal administration in ponies. RESULTS: Randomly selected clones from the 49th passage were all ts with plaquing efficiencies of < 10(-6) (ratio of 39.5 C:34 C) and retained this phenotype after 5 serial passages at 34 C in either embryonated eggs or MDCK cells. The clone selected as the vaccine candidate (P821) had the desired degree of attenuation. Administered intranasally to seronegative ponies, the virus caused no adverse reactions or overt signs of clinical disease, replicated in the upper portion of the respiratory tract, and induced a strong serum antibody response. CONCLUSION AND CLINICAL RELEVANCE: A candidate live attenuated influenza vaccine virus was derived by cold-adaptation of a wild-type equine-2 influenza virus, A/Equine/Kentucky/1/91, in embryonated eggs.

Animals↗

PubMed1989

Use of a gonadotropin-releasing hormone agonist during ovarian stimulation leads to significant concentrations of peptide in follicular fluids.

The penetration of a gonadotropin-releasing hormone agonist (GnRH-a), Buserelin (Hoechst AG, Frankfurt, West Germany), into human follicular fluids (FF) was studied by means of a radioimmunoassay (RIA) and a bioassay. Acute nasal administration of a therapeutic dose of Buserelin (300 and 600 micrograms) before the ovum pickup for in vitro fertilization leads to significant concentrations of Buserelin in one-third of the FF. These concentrations ranged between 28 and 124 pg/ml, which represents 10% to 50% of the serum concentrations achieved in these patients. Follicular penetration of this agonist is time-dependent. Chronic administration during the follicular phase leads to low but significant concentrations of peptide 36 hours after the last inhalation. A very good correlation was observed between the RIA and the bioassay. This demonstrates the accuracy and the specificity of the RIA. In addition, it indicates that the Buserelin that reaches follicles is intact and is not the inactive product of degradation. Intranasal administration of Buserelin stopped 35 hours before ovum pickup appears to be an adequate way of minimizing the exposure of maturing oocytes to the GnRH-a.

Adult↗

PubMedDate not supplied

Hemolytic activity of plasma and urine from rabbits experimentally infected with Legionella pneumophila.

Rabbits were infected with Legionella pneumophila by intravenous administration of allantoic fluid from eggs infected with this organism. Heated plasma from animals with severe illness caused by L. pneumophila lysed erythrocytes from guinea pigs in a radial hemolysis assay. Plasma from control rabbits did not lyse guinea pig erythrocytes in parallel assays. Urine from two of the infected animals also showed hemolytic activity. Attempts to induce illness in rabbits by intranasal administration of L. pneumohpila were less successful. Allantoic fluid from embrynated hen eggs developed hemolytic activity when maintained eithr in vitro at room temperature or in eggs whose embryos were killed by refrigeration. Hemolytic activity in filtrates of allantoic fluid from eggs infected with L. pneumophila, as previously reported, may not be due to the presence of bacterial hemolysins in the fluid.

Allantois↗

PubMed1993

Infarcted intramural uterine leiomyomata during buserelin acetate treatment.

Using continuous administration of gonadotropin releasing hormone analogues (GnRH-analogue) to induce a hypoestrogenic state and amenorrhea, leading to uterine fibroid volume reduction, has been reported to be successful and acceptable. Only a few adverse effects related to the therapy have been reported. We report a case of acute onset of abdominal pain, increased sedimentation rate and low grade fever during treatment with intranasal administration of Buserelin acetate. An emergent myomectomy was performed to remove an infarcted intramural myoma. We propose that acute ischemia of a large leiomyoma, especially during the postpartum period, is a noticeable complication during medical treatment with buserelin acetate for uterine leiomyoma.

Adult↗

PubMed1987

Calcitonin-induced hypocalcaemia as a possible index of osteoclastic activity in patients with chronic renal failure.

It has been suggested that the intensity of hypocalcaemic response to the administration of calcitonin may reflect the degree of osteoclastic activity and thus the state of the parathyroid function. We have performed the calcitonin test in 14 healthy volunteers and in 17 patients with chronic renal failure undergoing haemodialysis. The test involved the intramuscular injection of 100 MRC units of synthetic salmon calcitonin, serum calcium being determined before and after 5 h of the injections of the hormone. In 7 of the patients, the test was repeated using intranasal administration by means of a spray of calcitonin. In renal patients, serum calcium fell from 9.73 +/- 0.76 to 7.88 +/- 1.01 mg/dl (1.85 +/- 0.67 mg/dl). In the control group, serum calcium fell from 9.51 +/- 0.56 to 8.89 +/- 0.34 mg/dl (0.62 +/- 0.35 mg/dl). The calcium fall in renal patients was significantly greater than in the control group (p less than 0.001). In patients there was a statistically significant correlation between the fall in serum calcium and the level of alkaline phosphatase, but no with the serum concentration of immunoreactive parathormone (C-Terminal). After intranasal calcitonin, serum calcium fell from 9.81 +/- 0.55 to 8.83 +/- 0.72 mg/dl (1.42 +/- 0.42 mg/dl), a reduction comparable to that obtained after the intramuscular injection of the hormone in the same patients (1.84 +/- 0.69 mg/dl). These results provide evidence of an increase in osteoclastic activity in chronic renal failure, perhaps reflecting parathyroid hyperfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1978

DDAVP (1-desamino-8-D-arginine-vasopressin) treatment of central diabetes insipidus--mechanism of prolonged antidiuresis.

DDAVP, 1-desamino-8-D-arginine-vasopressin, is a synthetic analog of arginine vasopressin which produces prolonged antidiuresis after intranasal administration to patients with complete central diabetes insipidus. We have studied the mechanism of the prolonged antidiuretic effect by specific radioimmunossay of DDAVP in plasma of patients and by in vitro studies on the adenylate cyclase-cylic AMP system of the rat outer renal medulla. When DDAVP was administredd to patients, all responded, but the duration of response among patients varied from 5-21 h. The peak level of DDAVP in plasma was achieved up to 4 h after administration indicating a slow absorption from the nasal mucosa. The disappearance time of DDAVP from plasma correlated significantly with the duration of antidiuresis, P less than 0.001. On a molar basis DDAVP was 3-fold greater than AVP in its stimulation of outer medullary adenylate cyclase activity and 10-fold greater than AVP in its stimulation of cyclic AMP content. The prolonged antidiuresis of intranasally administered DDAVP is due to slow absorption, presistence in plasma, and enchanced effect on the kidney.

Adenylyl Cyclases↗