scholarly journals Long-Term Intranasal Insulin Aspart: A Profile of Gene Expression, Memory, and Insulin Receptors in Aged F344 Rats

2019 ◽  
Vol 75 (6) ◽  
pp. 1021-1030 ◽  
Author(s):  
Hilaree N Frazier ◽  
Adam O Ghoweri ◽  
Emily Sudkamp ◽  
Eleanor S Johnson ◽  
Katie L Anderson ◽  
...  

Abstract Intranasal insulin is a safe and effective method for ameliorating memory deficits associated with pathological brain aging. However, the impact of different formulations and the duration of treatment on insulin’s efficacy and the cellular processes targeted by the treatment remain unclear. Here, we tested whether intranasal insulin aspart, a short-acting insulin formulation, could alleviate memory decline associated with aging and whether long-term treatment affected regulation of insulin receptors and other potential targets. Outcome variables included measures of spatial learning and memory, autoradiography and immunohistochemistry of the insulin receptor, and hippocampal microarray analyses. Aged Fischer 344 rats receiving long-term (3 months) intranasal insulin did not show significant memory enhancement on the Morris water maze task. Autoradiography results showed that long-term treatment reduced insulin binding in the thalamus but not the hippocampus. Results from hippocampal immunofluorescence revealed age-related decreases in insulin immunoreactivity that were partially offset by intranasal administration. Microarray analyses highlighted numerous insulin-sensitive genes, suggesting insulin aspart was able to enter the brain and alter hippocampal RNA expression patterns including those associated with tumor suppression. Our work provides insights into potential mechanisms of intranasal insulin and insulin resistance, and highlights the importance of treatment duration and the brain regions targeted.

2004 ◽  
Vol 16 (6) ◽  
pp. 319-325 ◽  
Author(s):  
Pierre S. Chue ◽  
Peter D'Hoore ◽  
J. Michael Ramstack

Chronic disorders such as schizophrenia require long-term treatment programs in order to maintain patients at the lowest level of symptomatology, reduce the likelihood of psychotic relapse, and support achievement of remission and recovery. Evidence suggests that treatment with long-acting injectable antipsychotics reduces the impact of partial compliance and provides predictable release of medication, assuring continuous therapeutic coverage. Until recently, only conventional antipsychotic agents were available in long-acting formulations, thereby foregoing the advantages of the atypical class. Atypical agents which are given orally have been shown to provide long-term efficacy and tolerability benefits compared with conventional agents, but are limited by the need for daily administration. The most recent pharmacological strategy to achieve optimal maintenance treatment has been to combine the benefits of an atypical antipsychotic with delivery in a water-based long-acting formulation. The first antipsychotic to achieve this combination – long-acting risperidone – may thus represent an important advance in the optimization of long-term treatment outcomes in patients with schizophrenia.


Spine ◽  
2006 ◽  
Vol 31 (26) ◽  
pp. 3061-3069 ◽  
Author(s):  
Steven J. Atlas ◽  
Yuchiao Chang ◽  
Robert B. Keller ◽  
Daniel E. Singer ◽  
Yen A. Wu ◽  
...  

2020 ◽  
Vol 60 (1) ◽  
pp. 13-7
Author(s):  
Lilik Indrayati ◽  
Fadhilah Tia Nur ◽  
Bambang Soebagyo

Background Epileptic seizures are a transient occurrence resulting from abnormal, excessive, or synchronous neural activity in the brain. Epilepsy requires long-term treatment, increasingly larger doses, and combination therapy. Anti-epileptic drugs (AEDs), especially valproic acid (VPA), are the main treatment of choice. Thrombocytopenia is the most common adverse event from AEDs. Objective To evaluate platelet counts in epileptic children receiving valproic acid monotherapy vs. polytherapy. Methods This analytic, observational, retrospective cohort study was conducted in children with epilepsy below 18 years of age and treated in Dr. Moewardi Hospital, Surakarta, Central Java. Subjects had received VPA treatment for at least 6 months, either as monotherapy or polytherapy. There were 40 subjects in each group (VPA monotherapy vs. VPA polytherapy). The exclusion criteria were patients who had thrombocytopenia and did not take valproic acid regularly. The data was taken from laboratory and the outcome assessed was decreasing of platelet count. Results  Administration of VPA as monotherapy vs. polytherapy was not significantly associated with incidence of thrombocytopenia. However, duration of VPA use > 2 years was associated with significantly greater proportion of thrombocytopenia, with OR 33.0 (95%CI 4.157 to 261.962; P=0.001) compared to VPA use < 2 years. Similarly, VPA dose of >30 mg/kg/day was significantly associated with greater proportion of thrombocytopenia, with OR 4.081 (95%CI 1.337 to 12.458; P=0.013) compared to <30 mg/kg/day dosage. Conclusion Incidence of thrombocytopenia is not significantly different between VPA as a  monotherapy and polytherapy. However, higher VPA dose and longer VPA duration are associated with higher proportion of thrombocytopenia.


2010 ◽  
Vol 06 ◽  
pp. 68
Author(s):  
Rosario Pivonello ◽  
Renata S Auriemma ◽  
Mariano Galdiero ◽  
Ludovica FS Grasso ◽  
Annamaria Colao ◽  
...  

This article discusses the impact of long-term treatment of acromegaly on cardiovascular, metabolic, respiratory and articular complications as well as on malignancies. The main goals of treatment of acromegaly include normalisation of biochemical markers of disease activity, improvement in signs and symptoms of the disease, removal or reduction of tumour mass and preservation of pituitary function, together with prevention of complications. Cardiovascular and respiratory complications are the main causes of morbidity and mortality, whereas neoplasms are a minor cause of increased risk of death. Other associated diseases are arthropathy, carpal tunnel syndrome and reproductive disorders. The prolonged elevation of growth hormone (GH) and insulin-like growth factor (IGF)-I levels results in premature death, whereas strong biochemical control improves wellbeing and restores life expectancy to normal.


1984 ◽  
Vol 321 (1) ◽  
pp. 45-54 ◽  
Author(s):  
Franca Cerrito ◽  
Maria Martire ◽  
Paolo Preziosi

2021 ◽  
Vol 9 ◽  
Author(s):  
Lorraine Stallard ◽  
Séamus Hussey

The impact of endoscopic and histological mucosal healing on outcomes in adult settings is impressive. Despite many clinical parallels, pediatric ulcerative colitis (UC) is set apart from adult disease in several respects. Many frequently used indices are not fully validated, especially in pediatric settings, and consensus on precise definitions in clinical settings are lacking. Endoscopic mucosal healing is an acceptable long-term treatment goal in pediatrics, but not histologic normalization. Early prediction of disease course in UC may allow treatment stratification of patients according to risks of relapse, acute severe colitis, and colectomy. Putative endoscopic and histologic predictors of poor clinical outcomes in adults have not held true in pediatric settings, including baseline endoscopic extent, endoscopic severity, and specific histologic characteristics which are less prevalent in pediatrics at diagnosis. In this mini-review we appraise predictive endoscopic and histologic factors in pediatric UC with reference to relapse, severe colitis, and colectomy risks. We recommend that clinicians routinely use endoscopic and histologic sores to improve the quality of clinical and research practice. The review summarizes differences between adult and pediatric prediction data, advises special consideration of those with primary sclerosing cholangitis, and suggests areas for future study in this field.


2016 ◽  
Vol 5 (4) ◽  
pp. 16-27
Author(s):  
V. T. Vayradyan ◽  
A. M. Mudunov ◽  
R. I. Azizyan ◽  
I. A. Zaderenko ◽  
S. B. Alieva ◽  
...  

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5163-5163
Author(s):  
Marie-Anne van Lierde ◽  
Filipo Serra ◽  
Larissa De Rop ◽  
Eric Strobbe ◽  
Karen MacDonald ◽  
...  

Abstract BACKGROUND. ImRx for CML is a long-term treatment. Patterns and prevalence of NA to ImRx remain largely unknown. Short-term NA trends may be indicative of long-term NA. Methods for clinical NA assessment vary in reliability. A multimethod approach is indicated. OBJECTIVE. Multimethod estimation of patterns and prevalence of ImRx NA in CML pts at baseline (BL) and follow-up (FU) at 90 days (90d), incl. BL to 90d changes. DESIGN AND PATIENTS. Data subset from prospective, 90d observational, open-label, multicenter study. 169 evaluable pts on ImRx for minimum 30d at enrollment [1]. METHODS OF NA ASSESSMENT. At BL (NA with prior ImRx) and 90d (NA during study): visual analog scale (VAS) for physicians (phs; mVAS), pts (pVAS), cos (cVAS); Basel Assessment of Adherence Scale for pts (pBAAS; structured interview re NA in past 4 weeks [4wks]); pts reported persistence (pPST); % clinic appointments (%CAPPTS) kept (if any scheduled). At 90d also: % of ImRx taken per pill count (%pts@ImRx). RESULTS. See Table 1. CONCLUSIONS. Intuitive adherence ratings (VAS) by phs, pts, and cos are very high and differ from those from structured interview, where about one-third of patients exhibited NA behavior in 4wks prior to BL and FU - despite high persistence. Pill count suggests patterns of under- and overtaking, with only 1 out 7 patients being perfectly adherent. Rate of clinic appointments may be affected by physician scheduling practices and collateral input is a function of availability of collateral person. Consenting to participate in the ADAGIO study did not reduce NA. Though patient self-reports in structured interview (pBAAS) and pill counts have inherent biases, both indices suggest that NA with ImRx may be similar to NA rates in other disease categories. Especially pBAAS and pill count may be useful rapid clinical assessment tools, with pBAAS having the benefit of validated categorical assessment (vs. continuous in other methods). Determinants of NA and the impact of NA on treatment outcomes must be examined. Table 1 - Multimethod Assessment of Non-Adherence with Imatinib Method BL 90d n M±SD/Min-Max M±SD/Min-Max P mVAS 164 95.0±7.6/60–100 94.9±9.9/0–100 ns pVAS 169 95.3±8.5/25–100 95.7±6.1/75–100 ns cVAS 56 97.1±5.1/80–100 97.4±5.1/75–100 ns %pts@ImRx 162 - 91.0±21.1/29.5–2002.2 71.0% @ < 100% ImRx 14.2% @ 100% ImRx n % NA % NA P pBAAS 163 36.2% 32.5% ns %CAPPTS 51 94.1% 88.2% 0.001 pPST 163 98.8% 100.0% ns


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