Changes in attitudes toward diabetes in nursing students at diabetes camp.

AIM: The research purpose was to determine whether exposure to residential diabetes camps affects attitudes toward diabetes care and management in nursing students. BACKGROUND: Summer camp for children with type 1 diabetes mellitus (T1D) provides a unique and engaging clinical environment for nursing students to learn about evolving diabetes care and to help children develop diabetes management skills. METHODS: This prospective, pretest/posttest study assessed student nurses' attitudes about diabetes, who attended one of four residential summer camps in the United States, using the Diabetes Attitude Survey 3 (DAS3). The survey was administered before and after clinical experience designed to fulfill experiential curricula requirements from various nursing programs. RESULTS: After attending diabetes camp, nursing students (N = 73) had a positive change in their attitudes regarding the need for special training and the psychosocial impact of diabetes. DISCUSSION: The diabetes camp clinical experience impacted nursing students' attitudes. Diabetes camps are a unique clinical setting that uses learned clinical knowledge and judgment to promote health and prevent disease and disability, supporting the integration of primary care and public health nursing.

Student pharmacists' service-oriented learning at a camp for children with type 1 diabetes mellitus.

BACKGROUND AND PURPOSE: To describe advanced pharmacy practice experience (APPE) students' active learning engagement and changes in self-reported comfort with diabetes care activities by attending an overnight camp for children with type 1 diabetes mellitus (T1DM). EDUCATIONAL ACTIVITY AND SETTING: Fourth-year pharmacy students spend one or two weeks at an overnight camp for children ages six to 18 years with T1DM as part of their APPE and assist with diabetes care activities while participating in daily living activities. Students complete a survey one week before and one week after camp where they self-report their comfort level performing 16 different diabetes-related tasks. FINDINGS: Students (n = 21) participate in hands-on active learning while volunteering at a camp for children with diabetes. Before camp, 40-61% of students reported comfort with diabetes care activities related to pharmacotherapy, monitoring, and lifestyle management. After camp, the percent of students reporting comfort with these tasks increased to 78-96%. Specific items with greatest improvement were: when to monitor ketone levels (+79%), use of insulin pens and pumps (+64%), treatment of hypoglycemia (+50%), and carbohydrate counting (+50%). SUMMARY: By attending and participating at an overnight camp for children with T1DM, APPE students self-report gain in comfort in performing many diabetes care-related tasks.

High efficiency intranasal drug delivery using Intravail® alkylsaccharide absorption enhancers.

A new class of alkylsaccharide transmucosal delivery enhancement agents are described that overcome the principal limitations preventing broad acceptance of intranasal administration for many potential applications in systemic drug delivery, namely, poor transmucosal absorption and damage to the nasal mucosa. This review will describe recent developments in use of these excipients in human clinical trials and preclinical studies along with their chemical and pharmacological properties and explore commercial implications of the use of these excipients in introduction of new intranasal formulations of peptidic and nonpeptidic drugs.

Nasal absorption of mixtures of fast-acting and long-acting insulins.

Mixtures of fast-acting and long-acting insulins were administered nasally to anesthetized, hyperglycemic rats in the presence and absence of tetradecyl-beta-d-maltoside (TDM). The fast-acting analogs, aspart insulin, lispro insulin and glulisine insulin, were all rapidly absorbed from the nose when applied individually with 0.125% TDM (T(max)=15min). One long-acting insulin analog, glargine insulin, was also absorbed from the nose when applied individually in the presence of 0.125% TDM (T(max)=60min). The other long-acting insulin analog, detemir insulin, was not soluble when formulated with 0.125% TDM. A series of mixtures (1:1) of the three rapid-acting insulins and long-acting glargine insulin were formulated with 0.125% TDM and applied nasally. The pharmacokinetic and pharmacodynamic profiles of the insulin mixtures reflected the additive contributions of both the rapid-acting and the long-acting insulins. These results support the possibility of formulating certain insulin mixtures in tandem to provide nasal insulin products that match the needs of patients with diabetes mellitus better than those currently available.

Reestablishment of the nasal permeability barrier to several peptides following exposure to the absorption enhancer tetradecyl-beta-D-maltoside.

Regular insulin, NPH insulin, glargine insulin, calcitonin, and human growth hormone were administered to rats nasally with 0.125% tetradecyl-beta-D-maltoside (TDM), or at various times after TDM treatment. Absorption of all five peptides was enhanced initially and diminished in a time-dependent manner as the interval between administration of TDM and the peptide increased. Changes in nasal morphology were also assessed via transmission electron microscopy (TEM) immediately after TDM treatment and at various times thereafter. TEM analysis demonstrated that 0.125% TDM caused a rapid and transient alteration in the morphology of the apical membrane surface. Fewer cilia were observed and cell-cell junctions were difficult to visualize, but no epithelial cell erosion was apparent. Two hours after TDM treatment, the apical membrane surface once again contained abundant cilia and cell-cell junctions were readily visualized. The complete recovery of the nasal permeability barrier to several different peptides following TDM administration and the concomitant histological evidence demonstrate that TDM treatment transiently perturbs the nasal mucosa to stimulate peptide drug absorption and does not produce irreversible damage to the cells that line the nasal cavity.

Oral ddAVP for nighttime urinary incontinence in characterized nursing home residents: a pilot study.

OBJECTIVES: To (1) identify abnormalities in arginine vasopressin (AVP, a water-conserving hormone) secretion and release in nursing home (NH) residents with nighttime urinary incontinence (UI); and (2) perform a pilot test of desmopressin acetate (ddAVP, a synthetic analog of the naturally occurring hormone) replacement in these residents. DESIGN: Diagnostic evaluation and open-label treatment trial. SETTING: Two community nursing homes in a metropolitan area. PARTICIPANTS: Male and female NH residents 65 years of age and older with nighttime UI. INTERVENTION: Characterizations of AVP status followed by a 7-day open-label trial of oral ddAVP (either 0.1 mg or 0.2 mg). MEASUREMENTS: Water deprivation test results, AVP levels, voided volumes, number of voids, incontinent episodes, number of nighttime checks found wet (out of 6 total checks per night). RESULTS: All participants had measurable AVP levels of 2.0 pg/mL or higher. Six of 10 individuals had an abnormal water deprivation test. Two of 4 participants on 0.2 mg of ddAVP and 2 of 6 participants on 0.1 mg had a 200 mL or more mean reduction in nighttime urine volume. Both ddAVP dosages yielded a mean reduction of 0.7 fewer nighttime wet checks found wet. One participant in each group developed hyponatremia (1 of 6 on 0.1 mg and 1 of 4 on 0.2 mg). Hyponatremia resolved with discontinuation of the drug. CONCLUSION: Both 0.1 mg and 0.2 mg of ddAVP given to carefully screened NH residents for 7 days produced a modest average reduction in nighttime urine volume and number of nighttime incontinent episodes that is likely of little clinical importance. The role of ddAVP in this population requires further research.

Correlation of tetradecylmaltoside induced increases in nasal peptide drug delivery with morphological changes in nasal epithelial cells.

The effect of tetradecylmaltoside (TDM) on nasal peptide drug absorption was assessed with four peptides of distinct molecular size: insulin (5.7 kDa), leptin (16 kDa), somatropin (22.1 kDa), and epoetin alfa (30.4 kDa). The nasal uptake of the smallest peptides, insulin and leptin, was significantly increased at a TDM concentration of only 0.06%. The uptake of somatropin was significantly increased when concentrations of 0.125% or more were used. The uptake of the largest peptide, epoetin alfa, was not significantly increased, in the presence of 0.125-0.5% TDM. Light microscopy revealed that formulations containing 0.125% TDM caused moderate alterations in nasal epithelial cell morphology, while higher concentrations of TDM (0.5%), caused more extensive morphological changes. Following treatment with 0.125% TDM, the distribution of cilia was altered and the number of pinocytotic vesicles was increased, at a time that correlated with increased nasal absorption of insulin. Consistent with these findings, FITC-insulin applied nasally in the absence of TDM did not enter nasal epithelial cells, whereas FITC-insulin co-administered with 0.125% TDM was internalized into the cells, with a uniform distribution, consistent with transcellular movement of the peptide through the cells.

Obstructive sleep apnea, nocturia and polyuria in older adults.

STUDY OBJECTIVE: The purpose of this study was to examine the relationship between nocturia and obstructive sleep apnea (OSA) in community dwelling older men and women. DESIGN: A repeated measures design was employed over a 24-hour period. SETTING: The study was conducted in a clinical research center. PARTICIPANTS: Thirty community-dwelling elders (mean age=65.5, SD=8.4 years) with symptoms of nocturia and sleep disordered breathing, volunteered to participate. Both men (n = 13) and women (n = 17) and minority subjects (African-Americans, n = 19; Caucasian, n = 11) were included in the study. INTERVENTIONS: NA. MEASUREMENTS: Blood specimens were collected every 4 hours, except for an 8-hour collection period overnight. Urine specimens were collected ad libitum and at the end of each data collection interval. Urine and blood specimens were analyzed for ANP and AVP content. Polysomnography was conducted using a full 18-channel montage. Apnea was defined as a decrease in airflow of > or = 90% for a minimum of 10 seconds. Hypopnea was defined as > or = 30% decrease in airflow and desaturations required a > or = 3% decrease in oxygen saturation for a minimum of 10 seconds. The apnea hypopnea index (AHI) was calculated as the sum of apneas and hypopneas divided by hours of sleep. RESULTS: Twenty of the thirty subjects were found to have clinically diagnosable OSA (AHI > or = 5). AVP excretion was not correlated with changes in AHI levels. Conversely, total urine output, plasma ANP and urine ANP excretion were significantly higher among subjects with higher AHI levels (> 15). CONCLUSION: In subjects with elevated AHI (> 15), nighttime urine production and ANP excretion are elevated.

Effects of the permeability enhancers, tetradecylmaltoside and dimethyl-beta-cyclodextrin, on insulin movement across human bronchial epithelial cells (16HBE14o-).

The permeability of human bronchial epithelial cells (16HBE14o(-)) to radiolabelled insulin ([125I]insulin) formulated in the absence or presence of two different saccharide-containing permeability enhancers was investigated. In the absence of either enhancer, mannitol permeability and transepithelial electrical resistance (R(TE)) remained essentially unaffected for the duration of a 2-h experiment. Addition of either 0.125% tetradecylmaltoside (TDM) or 1% dimethyl-beta-cyclodextrin (DMBCD) to the apical surface of cells resulted in increased mannitol permeability and decreased R(TE), suggesting a loosening of cellular tight junctions and a concomitant increase in paracellular movement. Addition of [125I]insulin to the apical side of 16HBE14o(-) cells in the absence or presence of 1% DMBCD resulted in little or no [125I]insulin movement to the basolateral chamber or degradation in the apical chamber. However, in the presence of 0.125% TDM, the amount of intact [125I]insulin remaining in the apical chamber was substantially decreased, while [125I]insulin and 125I-labeled fragments were recovered on the basolateral side of the cells after 2 h. These findings provide evidence that the loosening of the tight junctions between cells achieved with DMBCD is not sufficient to stimulate transepithelial insulin movement, whereas exposure to 0.125% TDM causes an increase in [125I]insulin permeation and degradation.

Arginine vasopressin and nocturnal polyuria in older adults with frequent nighttime voiding.

PURPOSE: We determined in older adults whether frequent nighttime voiding is associated with urine overproduction at night or nocturnal polyuria (NP) and whether NP is associated with abnormalities of arginine vasopressin (AVP) blood levels and/or renal responsiveness to AVP. MATERIALS AND METHODS: We used a convenience sample of adults 65 years and older in home and general clinical research center settings. A total of 45 participants completed the 3-day general clinical research center stay. We used 7-day voiding diaries to determine which participants had 2 or greater nighttime voids and NP, defined as 35% or greater of 24-hour urine output at night. Abnormalities in AVP release and secretion were determined by water deprivation testing and by twice daily blood AVP measurement. RESULTS: There was a strong positive association between the number of nighttime voids and the proportion of urine produced at night (r = 0.6, p <0.001). There was no association between NP and AVP blood levels or action. Participants with and without NP had similar maximum urine osmolality following water deprivation and exogenous AVP administration (mean 549 mOsm, range 422 to 713 and 547 mOsm, range 353 to 692, respectively). CONCLUSIONS: We found no association between NP and AVP abnormalities in this sample of older adults. Study participants had low maximal urine osmolality in response to fluid deprivation and exogenous vasopressin administration irrespective of whether they were identified as having NP.

Sucrose cocoate, a component of cosmetic preparations, enhances nasal and ocular peptide absorption.

Sucrose cocoate (SL-40), an emulsifier employed in emollient, skin-moisturizing cosmetic formulations, contains a mixture of sucrose esters of coconut fatty acids in aqueous ethanol solution. In order to determine its potential utility in enhancing nasal and ocular drug delivery, absorption studies were performed in anesthetized Sprague-Dawley male rats with calcitonin and insulin, two distinct therapeutic peptides. Administration of a nasal insulin formulation containing 0.5% sucrose cocoate caused a rapid and significant increase in plasma insulin levels, with a concomitant decrease in blood glucose levels. When insulin was administered ocularly in the presence of 0.5% sucrose cocoate, a smaller increase in plasma insulin levels, and a decrease in blood glucose levels, were observed. Administration of a nasal calcitonin formulation containing 0.5% sucrose cocoate caused a rapid increase in plasma calcitonin levels and a concomitant decrease in plasma calcium levels. Mass spectrometric analyses were used to characterize the nature of the sucrose fatty acid esters in the mixture. The most abundant sucrose ester in sucrose cocoate was sucrose monododecanoate, with smaller amounts of sucrose monodecanoate and sucrose monotetradecanoate. In vivo experiments confirmed that this ester was an effective enhancer of nasal peptide drug absorption.

Nasal administration of low molecular weight heparin.

The main objective of this study was to determine if the systemic absorption of therapeutic amounts of heparin was possible following nasal administration. Sprague-Dawley rats received nosedrops containing a low molecular weight heparin (LMWH) or unfractionated heparin (UFH) formulated with or without tetradecylmaltoside (TDM). TDM is a nonionic surfactant that has been previously shown to be a potent absorption enhancer in studies with peptide drugs. LMWH/UFH absorption was determined by measuring plasma anti-Factor Xa activity. The inclusion of 0.25% TDM in nasal formulations containing LMWH resulted in a significant increase in the C(max) and area under the curve (AUC) of anti-Factor Xa activity when compared to LMWH formulated in saline alone. The addition of TDM to a nasal formulation containing UFH resulted in a much smaller increase in the C(max) and the AUC of anti-Factor Xa activity. The absolute bioavailability of LMWH was increased from 4.0 +/- 0.4% in the absence of TDM to 19 +/- 0.3% in the presence of TDM. The reversibility of the absorption enhancing effect of TDM was studied by applying LMWH nasally 60 or 120 min after the enhancer. The effect of TDM on the nasal epithelia appeared to be rapidly reversible. In conclusion, nasal delivery of LMWH, but not UFH, was successful when an absorption enhancer was included to increase nasal permeability.

Synthetic long-chain alkyl maltosides and alkyl sucrose esters as enhancers of nasal insulin absorption.

A series of new glycosides with extended alkyl side-chains (C(13-16)) linked to maltose or sucrose were synthesized and tested for their efficacy in enhancing nasal insulin absorption in anesthetized rats. The new reagents were compared to previously tested alkylglycosides with shorter alkyl side chains (C(8-12)). Dose-response studies revealed that within the family of alkylmaltoside derivatives, (C(8-16)), maximal increases in insulin absorption took place when tetradecylmaltoside (C(14)) was added to the formulation. Pentadecylmaltoside (C(15)) and hexadecylmaltoside (C(16)) were less potent at increasing insulin absorption, although both reagents achieved maximal effects when used at higher concentrations. Within the family of alkanoylsucrose derivatives, tridecanoylsucrose (C(13)) and tetradecanoylsucrose (C(14)) were most potent at increasing insulin absorption. Cross-comparisons between alkylmaltoses and alkanoylsucroses showed that the alkyl chain length had a greater impact than the glycoside moiety in determining the potency of a potential insulin-absorption enhancing agent. When tetradecylmaltoside was applied to the nasal mucosa 15 min before insulin was applied, the enhanced insulin absorption was still observed.

Nocturnal polyuria in type 2 diabetes: a symptom of obstructive sleep apnea.

PURPOSE: Polyuria and nocturia in individuals with type 2 diabetes may be due to obstructive sleep apnea (OSA), a recently recognized etiology of excess nighttime urine production. This exploratory study examined the relationships among glucose control, OSA, and nocturnal urine production. METHODS: A sample of community-dwelling older adults (20 nondiabetic subjects and 10 poorly controlled type 2 diabetes subjects) was recruited based on self-report of nocturia more than twice per night. Participants were monitored on a metabolic research unit for 24 hours to track intake/output, collect blood and urine samples, and conduct an overnight polysomnography sleep study. RESULTS: None of the subjects had fasting serum glucose levels above the renal threshold. OSA was found in 65% of subjects. Those with moderate/severe OSA had significantly greater overnight urine production than subjects without OSA. Subjects with type 2 diabetes and moderate/severe OSA had the highest nocturnal urine production. CONCLUSIONS: The high incidence of undetected OSA in subjects with type 2 diabetes with nocturia suggests that nocturia, OSA, and type 2 diabetes frequently coexist and may be interrelated.

Misoprostol Modulation of Dendritic Cell Function in Immune Responses.

Dendritic cells (DC) from blood and other tissues are potent accessory cells for primary immune responses. Because prostaglandins from monocytes and macrophages can suppress DC and T-cell function, we sought to investigate the binding properties of misoprostol (MPL), a prostaglandin E(1) analog, and its regulation of DC function. Results of mouse and human experiments have suggested 1) that MPL could significantly inhibit DC-induced T-cell proliferation in oxidative mitogenesis and allogeneic mixed leukocyte reactions by decreasing interleukin-2 production in DC-T cell cocultures, and 2) that MPL could bind to human peripheral blood mononuclear cells via specific high-affinity MPL binding sites as well as through nonspecific MPL uptake. Taken together, these data suggest that MPL can bind high-affinity and/or nonspecific cell surface receptors and subsequently regulate T-cell growth and cytokine production such as that induced by DC and associated with primary immune responses.