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G Perret

Publications and source records attributed to G Perret.

At least 19 recordsLinked to original sources
PubMed2005

Sudden, unexpected death due to undiagnosed frontal glioblastoma in a schizophrenic patient.

The incidence of sudden death due to undiagnosed primary intracranial tumor is low in forensic autopsy. We report a case of a 48-year-old white male, known to be a schizophrenic patient for several years, and in whom a medico-legal autopsy disclosed a large, previously undiagnosed, bilateral frontal glioblastoma infiltrating the genu of corpus callosum. We emphasize the importance of performing complete autopsy, including a thorough neuropathological examination, in all cases of sudden unexpected death, especially in those cases in which no extracerebral cause of death had been established and whose clinical history was primarily of a psychiatric nature.

Brain Neoplasms↗
PubMed2005

Integrative analysis of gene expression patterns predicts specific modulations of defined cell functions by estrogen and tamoxifen in MCF7 breast cancer cells.

To explore the mechanisms whereby estrogen and antiestrogen (tamoxifen (TAM)) can regulate breast cancer cell growth, we investigated gene expression changes in MCF7 cells treated with 17beta-estradiol (E2) and/or with 4-OH-TAM. The patterns of differential expression were determined by the ValiGen Gene IDentification (VGID) process, a subtractive hybridization approach combined with microarray validation screening. Their possible biologic consequences were evaluated by integrative data analysis. Over 1000 cDNA inserts were isolated and subsequently cloned, sequenced and analyzed against nucleotide and protein databases (NT/NR/EST) with BLAST software. We revealed that E2 induced differential expression of 279 known and 28 unknown sequences, whereas TAM affected the expression of 286 known and 14 unknown sequences. Integrative data analysis singled out a set of 32 differentially expressed genes apparently involved in broad cellular mechanisms. The presence of E2 modulated the expression patterns of 23 genes involved in anchors and junction remodeling; extracellular matrix (ECM) degradation; cell cycle progression, including G1/S check point and S-phase regulation; and synthesis of genotoxic metabolites. In tumor cells, these four mechanisms are associated with the acquisition of a motile and invasive phenotype. TAM partly reversed the E2-induced differential expression patterns and consequently restored most of the biologic functions deregulated by E2, except the mechanisms associated with cell cycle progression. Furthermore, we found that TAM affects the expression of nine additional genes associated with cytoskeletal remodeling, DNA repair, active estrogen receptor formation and growth factor synthesis, and mitogenic pathways. These modulatory effects of E2 and TAM upon the gene expression patterns identified here could explain some of the mechanisms associated with the acquisition of a more aggressive phenotype by breast cancer cells, such as E2-independent growth and TAM resistance.

Breast Neoplasms↗
PubMed2003

Carboxymethyl benzylamide dextran inhibits angiogenesis and growth of VEGF-overexpressing human epidermoid carcinoma xenograft in nude mice.

Vascular endothelial growth factor (VEGF) expression is elevated in a wide variety of solid tumours. Inhibition of VEGF activities is able to reduce angiogenesis and tumour growth. We have recently shown in vitro that carboxymethyl dextran benzylamide (CMDB7) prevents the binding of VEGF(165) to its cell surface receptors and thus inhibits VEGF activities on endothelial cells. In the present study, we explored the effects of CMDB7 on highly aggressive human epidermoid carcinoma A431 cells known to overexpress epidermal growth factor receptors (EGFRs) and produce a high amount of VEGF and a minor quantity of bFGF. In vitro, CMDB7 blocked the mitogenic activity of A431-conditioned medium on endothelial cells. Concerning A431 cells, CMDB7 inhibited their proliferation and the VEGF(165) binding to them. In vivo, administration of CMDB7 (10 mg kg(-1)) three times per week for 2 weeks inhibited the growth of A431 xenografts in nude mice by 73% as compared to the control group. Immunostaining of endothelial cells with mouse-specific GSL-1 lectin in tumour sections revealed that CMDB7 also inhibited the density of intratumour endothelial cells by 66%. These findings demonstrate that CMDB7 has an efficient antiangiogenic and antitumour action in vivo even when tumour cells produce a high level of VEGF and EGFRs.

Animals↗
PubMed2001

Sodium phenylacetate enhances the inhibitory effect of dextran derivative on breast cancer cell growth in vitro and in nude mice.

Sodium phenylacetate (NaPa) and carboxymethyl benzylamide dextran derivative (CMDB(LS4)) are able to inhibit growth of breast tumour cells. In this study, we explored whether the combination of NaPa and CMDB(LS4)may enhance their respective inhibitory effects on the MCF-7ras cell growth in vitro and in vivo. NaPa inhibited MCF-7ras cell proliferation by reducing the DNA replication concomitantly with a recruitment of cells in G0/G1 phase and by inducing apoptosis in a dose- and time-dependent manner. The addition of CMDB(LS4)potentiated the NaPa antiproliferative effect in the manner dependent on the ratio of CMDB(LS4)and NaPa concentrations. In nude mice, CMDB(LS4)(150 mg kg(-1)) or NaPa (40 mg kg(-1)) administrated twice a week, for 7 weeks inhibited MCF-7ras xenograft growth by 40% and 60%, respectively. The treatment by both, CMDB(LS4)and NaPa, decreased tumour growth by 83% without any toxicity. To better understand the mechanism of NaPa and CMDB(LS4)action we assessed their effect on mitogenic activity of MCF-7ras conditioned medium (CM) on BALBC/3T3 fibroblasts. CMDB(LS4)added to the CM, inhibited its mitogenic activity whereas NaPa had an anti-mitogenic effect when CM was prepared from MCF-7ras cells pretreated with NaPa. Thus, the antiproliferative effects of NaPa and CMDB(LS4)involve 2 different mechanisms explaining, at least in part, the possible synergism between them. Overall, this study points to the potential use of a combination of dextran derivatives with NaPa to inhibit the breast tumour growth.

3T3 Cells↗
PubMed2001

Vascular endothelial growth factor 165 (VEGF(165)) activities are inhibited by carboxymethyl benzylamide dextran that competes for heparin binding to VEGF(165) and VEGF(165).KDR Complexes.

We have previously shown that carboxymethyl dextran benzylamide (CMDB7), a heparin-like molecule, inhibits the growth of tumors xenografted in nude mice, angiogenesis, and metastasis by altering the binding of angiogenic growth factors, including platelet-derived growth factor, transforming growth factor beta, and fibroblast growth factor 2, to their specific receptors. In this study, we explore the effect of CMDB7 on the most specific angiogenic growth factor, vascular endothelial growth factor 165 (VEGF(165)). We demonstrate here that CMDB7 inhibits the mitogenic effect of VEGF(165) on human umbilical vein endothelial cells (HUV-ECs) by preventing the VEGF(165)-induced VEGF receptor-2 (KDR) autophosphorylation and consequently a specific intracellular signaling. In competition experiments, the binding of (125)I-VEGF(165) to HUV-ECs is inhibited by CMDB7 with an IC(50) of 2 microm. Accordingly, CMDB7 inhibits the cross-linking of (125)I-VEGF(165) to the surface of HUV-ECs, causing the disappearance of both labeled complexes, 170-180 and 240-250 kDa. We show that CMDB7 increases the electrophoretic mobility of VEGF(165), thus evidencing formation of a stable complex with this factor. Moreover, CMDB7 reduces the (125)I-VEGF(165) binding to coated heparin-albumin and prevents a heparin-induced increase in iodinated VEGF(165) binding to soluble (125)I-KDR-Fc chimera. Concerning KDR, CMDB7 has no effect on (125)I-KDR-Fc electrophoretic migration and does not affect labeled KDR-Fc binding to coated heparin-albumin. In the presence of VEGF(165), (125)I-KDR-Fc binding to heparin is enhanced, and under these conditions, CMDB7 interferes with KDR binding. These data indicate that CMDB7 effectively inhibits the VEGF(165) activities by interfering with heparin binding to VEGF(165) and VEGF(165).KDR complexes but not by direct interactions with KDR.

Angiogenesis Inhibitors↗
PubMed2000

Identification of a peptide blocking vascular endothelial growth factor (VEGF)-mediated angiogenesis.

Vascular endothelial growth factor (VEGF) binding to the kinase domain receptor (KDR/FLK1 or VEGFR-2) mediates vascularization and tumor-induced angiogenesis. Since there is evidence that KDR plays an important role in tumor angiogenesis, we sought to identify peptides able to block the VEGF-KDR interaction. A phage epitope library was screened by affinity for membrane-expressed KDR or for an anti-VEGF neutralizing monoclonal antibody. Both strategies led to the isolation of peptides binding KDR specifically, but those isolated by KDR binding tended to display lower reactivities. Of the synthetic peptides corresponding to selected clones tested to determine their inhibitory activity, ATWLPPR completely abolished VEGF binding to cell-displayed KDR. In vitro, this effect led to the inhibition of the VEGF-mediated proliferation of human vascular endothelial cells, in a dose-dependent and endothelial cell type-specific manner. Moreover, in vivo, ATWLPPR totally abolished VEGF-induced angiogenesis in a rabbit corneal model. Taken together, these data demonstrate that ATWLPPR is an effective antagonist of VEGF binding, and suggest that this peptide may be a potent inhibitor of tumor angiogenesis and metastasis.

Amino Acid Sequence↗
PubMed2000

Lethal methadone intoxications in Geneva, Switzerland, from 1994 to 1998.

AIMS: To estimate the number of methadone lethal intoxications in Geneva from 1994 to 1998, where the number of patients in methadone treatment has more than doubled since 1990. DESIGN: Retrospective study of all toxicological, autopsy and clinical data. SETTING: The Geneva Department of Forensic Medicine. PARTICIPANTS: All suspected overdose deaths in Geneva from 1994 to 1998. Cases were selected on the basis that the only cause of death was a potentially lethal drug concentration in the postmortem blood sample. MEASUREMENT: Toxicology and autopsy findings, clinical and drug history. FINDINGS: There were 106 lethal drug intoxications over the period. The overall number of drug intoxication deaths went from 33 in 1994 to nine in 1998. Thirty-six cases had methadone identified in their blood. All the 36 cases but one had medications or other drugs used illicitly present in the blood or urine. Of these 36 cases, 21 were attributed to methadone lethal intoxication. Only seven of these 21 decedents were enrolled in a methadone programmes. The number of deaths attributed to methadone intoxication ranged from three to five per year. CONCLUSION: Most lethal methadone intoxication is due to diverted or illegal methadone in association with medications or other drugs used illicitly. Furthermore, the increase in methadone prescription under strict medical control with health measures aimed at drug abuse prevention did not lead, in our study, to an increase of methadone lethal intoxication and may have been partly responsible for the large decrease of overall drug intoxication deaths during the time of our study.

Adolescent↗
PubMed2000

[L-tryptophan plasma levels in treatment resistant depressive states].

10 to 30% of depressions are resistant to standard treatment. Different therapeutic strategies are used to treat the resistant depressions. Therefore, before initiating an antidepressant treatment, it would be important to know which patients will probably not respond to a standard treatment. Numerous studies have shown that serotonin is involved in depressive illness and its synthesis in the brain is dependent on the availability of tryprophan from plasma. As tryptophan plasma level is decreased in depression, resistant depressions may also be characterized by alterations of tryptophan plasma level. 141 depressed patients were admitted in our psychiatric unit in Geneva between 1984 and 1990. 36 were diagnosed as treatment resistant depression. Although treatment resistant patients group had more women and a more severe score of depression on the AMDP-4 scale, we did not observe a significant difference in tryptophan plasma level compared to patients who respond to treatment.

Adult↗
PubMed2000

[Hemodynamic consequences of endogenous hyperinsulinism in obese rats with lesions of the ventromedial hypothalamus].

The rat with ventromedian hypothalamus lesions (VMH) is characterized by massive obesity, hyperinsulinemia, increase in parasympathetic tonus and sympathetic depression. The aim of this study was to examine in this model the hemodynamic changes and the baroreflex response and to compare the data with the evaluation of beta adrenergic sensitivity. In VMH rats and Sham operated rats hemodynamic parameters were followed until 8 weeks after operation. Heart rate (HR) and blood pressure (BP) were monitored each week during 24 hours by a telemetric system, a catheter being implanted in aorta. In VMH, HR was significantly lower by the first week (p = 0.02) and until the last measurement. Systolic BP increased progressively in the two groups but was higher in VMH only at 8 weeks (p = 0.03). Compared with Sham rats, 5 days after operation, the percentage of HR acceleration in response to atropine and isoprenaline was significantly higher in VMH, whereas HR response to sodium nitroprussiate was similar in the two groups. Plasma epinephrine and norepinephrine levels were significantly higher in VMH rats. The density of cardiac beta receptors decreased from 15 days to 3 months after operation, similarly in VMH and Sham rats. The affinity of cardiac beta receptors remained stable during the same period and very similar in VMH and Sham rats. This study suggests that in VMH rats 1. bradycardia results mainly from an increase in parasympathetic tone; 2. the increase in reflex tachycardia described in normal rats after insulin infusion needs a normal activity of the sympathetic nervous system; 3. catecholamine levels may be increased despite sympathetic depression, probably as a result of an increase in adrenomedullary secretion possibly due to endogenous hyperinsulinemia; 4. the lack of hypertension in this model including a massive obesity is likely to result from the proper vasodilatory effect of insulin.

Adrenergic Agonists↗
PubMed1998

Downregulation of 5-HT1A receptors in rat hypothalamus and dentate gyrus after "binge" pattern cocaine administration.

The effect of chronic cocaine exposure on the central serotonergic system in the rat was investigated using a selective 5-HT1A receptor agonist, [3H]8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT), and a 5-HT2A receptor antagonist, [3H]ketanserin, as tritiated ligands in a quantitative autoradiography study. Rats were administered cocaine in a "binge" pattern, 15 mg/kg/injection, three times a day, at 1-h intervals for 14 days to mimic the pattern often seen in human cocaine addicts. A significant decrease in the binding of [3H]8-OH-DPAT was found in the ventromedial hypothalamus (P < 0.001) and the dorsal dentate gyrus (P < 0.01) in rats administered cocaine as compared with rats injected with saline. No significant difference in the binding of [3H]ketanserin was found in frontal, parietal, agranular insular, and piriform cortices, caudate-putamen, olfactory tubercle, nucleus accumbens, thalamus, septohippocampal nucleus, and claustrum. Several studies have shown that 5-HT1A receptor agonists have antidepressant properties. Other studies, in animal models, have shown that 5-HT1A receptor agonists stimulate the hypothalamic-pituitary-adrenal axis, which is of interest, since chronic activation of this axis has been related to anxiety and depression. Our data show that the 5-HT1A component of the serotonergic system is altered following chronic "binge" pattern cocaine administration in an animal model and may be related to changes in the HPA axis and behavior.

Animals↗
PubMed1998

Nalmefene causes greater hypothalamic-pituitary-adrenal axis activation than naloxone in normal volunteers: implications for the treatment of alcoholism.

Among other actions, opioid antagonists modulate the control endogenous opioids exert on the hypothalamic-pituitary-adrenal (HPA) axis. Naloxone, nalmefene, and naltrexone are the opioid antagonists approved for use in man and are primarily mu-opioid selective. Naltrexone and nalmefene have been demonstrated to be useful in the treatment of alcoholism. Compared with naloxone, nalmefene has a longer half-life, is more potent at the mu-receptor, and has a higher affinity for kappa- and delta-opioid receptors. We conducted an inpatient study comparing the effects of 10 and 30 mg doses of intravenous naloxone and nalmefene in normal, nonsubstance nor alcohol-abusing, volunteers. Significant increases in ACTH and cortisol were observed after both antagonists, without an apparent dose-response relationship; however, both doses of nalmefene resulted in greater HPA axis activation than either dose of naloxone (ACTH: p <0.005). These results indicate that kappa- and delta-opioids may play important roles in the regulation of the HPA axis; nalmefene may be useful as both a probe to explore the HPA axis physiology and as a pharmacotherapeutic agent.

Adrenocorticotropic Hormone↗
PubMed1998

Analysis of the pharmacokinetic interaction between cephalexin and quinapril by a nonlinear mixed-effect model.

Oligopeptidic drugs such as beta-lactams and angiotensin-converting enzyme inhibitors share the same carriers in humans and animals, which results in possible pharmacokinetic interactions. To model such interactions, the effects of quinapril on cephalexin pharmacokinetics were investigated in rats. Blood cephalexin concentrations were measured by liquid chromatography, and the data were analyzed by a noncompartmental method and by fitting a bicompartmental model by a nonlinear mixed-effect modeling approach. Five groups of eight rats were examined. In the first three groups, cephalexin elimination kinetics after intra-arterial administration alone or in combination with quinapril given by the parenteral or the oral route were studied, and the occurrence of a pharmacokinetic interaction was not revealed. The absence of an effect of quinapril on cephalexin elimination after parenteral administration might be explained either by the higher affinity of cephalexin for the renal anionic transport system than that of quinapril or by the much higher concentrations of cephalexin than those of quinapril. In the last two groups, cephalexin was administered by the oral route alone or in combination with quinapril. The mean area under the concentration-time curve (AUC) for cephalexin was increased by ca. 30% by coadministration of quinapril (40.1 versus 31.4 mg.h/liter; P = 0.04). The mean elimination clearance of cephalexin was significantly decreased by quinapril, from 0.81 to 0.64 liter/h/kg of body weight (P < 0.05), probably by competitive inhibition of cephalexin secretion at the tubular level. The mean absorption rate constant of cephalexin was significantly lowered by quinapril (from 0.249 to 0.177 h-1; P < 0.01), without modification of the extent of absorption (89%). This pharmacokinetic interaction could be explained by competitive inhibition of cephalexin active transport by quinapril at the intestinal level.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Predictive value of serum sex hormone binding globulin for the occurrence of hepatocellular carcinoma in male patients with cirrhosis.

BACKGROUND/AIMS: The incidence of hepatocellular carcinoma is higher in males, presumably due to the influence of sex steroids. Therefore, to further assess the role of sex steroids in the occurrence of hepatocellular carcinoma, this study investigated the predictive value of different sex hormones and their binding protein. METHODS: Among 101 male patients with cirrhosis included in a prospective screening study, 29 developed hepatocellular carcinoma. We assessed the predictive value of 17 clinico-biological and 4 serum hormonal variables collected at enrollment, by the log-rank test and the Cox model. RESULTS: Age (p = 0.003), bilirubin (p = 0.04), sex-hormone-binding-globulin (p = 0.006) and albumin (p = 0.08) were predictive using the log-rank test, while estradiol and total and free testosterone were not. The Cox model showed age (p = 0.0003; relative risk = 7.52), sex-hormone-binding globulin (p = 0.001, relative risk = 3.37) and albumin (p = 0.02, relative risk = 2.94) as the most predictive parameters. CONCLUSION: We conclude that high serum sex-hormone-binding-globulin levels have an independent predictive value for the occurrence of hepatocellular carcinoma. Serum sex-hormone-binding-globulin could be used to define patients at high risk for hepatocellular carcinoma and could hypothetically play a role in hepatocarcinogenesis.

Carcinoma, Hepatocellular↗
PubMed1997

Impairment of antidiuretic hormone and atrial natriuretic peptide regulation in the obese woman with a swelling syndrome and an increase in capillary permeability to albumin.

OBJECTIVE: To study the regulation of antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) in obese and lean women with a swelling syndrome. PATIENTS: Thirty-four obese women and 12 lean women with a swelling syndrome and an abnormal isotopic test of capillary permeability to albumin were investigated. MEASUREMENTS: After 10 nocturnal hours of fluid restriction, subjects were asked at 8am to ingest a tap water load of 20 ml/kg within 10 min and to remain strictly recumbent until twelve noon on the first day, and to remain standing and to walk around until twelve noon on the second day. Free water clearance and the cGMP/creatinine and albumin/creatinine ratios were determined hourly in the morning. RESULTS: The total 4 h-urinary volume/ingested water volume ratio was significantly lower on the second day both in the lean and the obese patients, the differences being slightly larger in the obese patients. The increase in free water clearance was significantly less on the second day in the obese patients. The increase in cGMP/creatinine ratio was also significantly lower on the second day in the obese patients. The maximum level of the urinary albumin/creatinine ratio was significantly higher on the second day in the obese patients. CONCLUSION: In obese women with a swelling syndrome: (1) The higher increase in the urinary albumin excretion rate after water loading followed by a sustained upright position suggests a widespread alteration in capillary function, which is also indicated by the isotopic test of capillary permeability to albumin. (2) The water load-induced inhibition of ADH secretion and stimulation of ANP secretion or ANP activity, more defective in the upright position than in the recumbent one, is probably another major contributing factor to orthostatic oedema.

Adult↗
PubMed1997

Short-term effects of continuous subcutaneous insulin infusion treatment on insulin secretion in non-insulin-dependent overweight patients with poor glycaemic control despite maximal oral anti-diabetic treatment.

It is difficult to treat obese non-insulin-dependent diabetic patients (NIDDs) whose glycaemic control remains poor despite maximal oral antidiabetic therapy. We studied the effect of a continuous subcutaneous insulin infusion (CSII) associated with a low-calorie diet and metformin 1,700 mg/day on glycaemic control and basal and stimulated insulin secretion in a series of 82 overweight NIDD before (T1), during CSII (T2), and after CSII withdrawal (T3). Patients were treated for 8 to 23 days with a mean amount of 0.50 +/- 0.02 IU/kg/day. Glycaemic control was very good after 3-5 days of CSII and remained good at T3. At T2, fasting and postprandial plasma C peptide levels decreased significantly. At T3, fasting C peptide was very similar to T1, and postprandial C peptide was significantly higher than at T1. The molar fasting and postprandial plasma C peptide/glycaemia ratios increased significantly at T3. After glucagon injection, the molar delta C peptide/glycaemia ratio was significantly increased at T2 and even higher at T3. At T2, as at T1 and T3, there were significant correlations between fasting and postprandial C peptide levels and between the glucagon-induced C peptide peak and fasting and postprandial C peptide levels. Between T1 and T3 weight changes correlated significantly with the molar fasting C peptide/glycaemia ratio at T1. Twenty-nine of the 30 patients for whom this ratio was > 6.6 x 10(-8) lost weight. The length of CSII treatment did not correlate with weight changes or other biological parameters. This study shows that CSII with moderate amounts of insulin associated with a low-calorie diet and metformin provided rapid glycaemic control, led to weight loss, maintained regulation of insulin secretion and seemed to improve insulin secretion and sensitivity. These results were obtained in only 8 to 10 days.

Administration, Cutaneous↗
PubMed1996

TSH and prolactin responses to thyrotropin releasing hormone (TRH) and domperidone in patients with empty sella syndrome.

The aim of this study was to investigate TSH and PRL response to TRH and domperidone, an antidopaminergic drug which does not cross the blood-brain barrier, in 16 patients with primary empty sella (PES) and either normal or elevated plasma PRL level and to compare it with the response observed in 8 patients with prolactinoma. In the patients with PES and hyperprolactinemia, the PRL response to TRH was significantly lower than in the controls and the patients with PES and normal PRL, which suggests there is impaired PRL synthesis and release in cases of PES with hyperprolactinemia. The TSH response to domperidone was significantly elevated in patients with PES and either normal or elevated PRL, as in patients with prolactinoma. The PRL response to domperidone was significantly reduced in patients with PES and hyperprolactinemia as in patients with prolactionoma. These results suggestthat in PES with prolactinoma the inhibiting dopaminergic tone is increased on the thyrotropic cells and reduced on the lactotropic cells in PES with elevated PRL and that some patients with PES might bear a microprolactinoma in the bottom of the sella which remained undetected by the CT scan.

Adult↗
PubMed1996

Effect of insulin concentration on bioavailability during nasal spray administration.

The bioavailability of rapid-acting insulin administered as a nasal spray was studied in 6 type 1 (insulin-dependent) diabetic patients. They received long-acting bovine insulin (Ultratardum 40 U/ml, Organon) as basal treatment at 8 a.m. Rapid-acting insulin was also administered at 8 a.m., then at noon and 6 p.m, subcutaneously on day 1 as a 100 U/ml solution and intranasally by aerosol spray as a 100 U/ml and 500 U/ml with 1% (w/v) 9 lauryl ether solution on day 2 and day 3 respectively. On days 2 and 3, the dose of insulin was at least nine times higher than the subcutaneous dose on day 1. Free and total plasma insulin concentrations were assayed after the noon insulin administration. The peaks of the free and total plasma insulin levels were reached earlier and the return to basal levels was obtained earlier after nasal insulin administration than after insulin injected subcutaneously. The bioavailability of nasal spray insulin versus subcutaneous insulin with a 100 U/ml insulin solution was similar to that with a 500 U/ml insulin solution: 5.14 +/- 0.38% (m +/- SEM) and 4.64 +/- 0.46% according to the total plasma insulin level. This study suggests that the bioavailability of nasal spray insulin is not increased by increasing insulin concentration in our experimental conditions.

Administration, Intranasal↗