scholarly journals Ghrelin Prevents Cisplatin-Induced Mechanical Hyperalgesia and Cachexia

Endocrinology ◽  
2007 ◽  
Vol 149 (2) ◽  
pp. 455-460 ◽  
Author(s):  
José M. Garcia ◽  
Juan P. Cata ◽  
Patrick M. Dougherty ◽  
Roy G. Smith

Complications induced by the chemotherapeutic agent cisplatin, such as neuropathy and cachexia, occur frequently, are often dose limiting, and have an impact on quality of life and survival in cancer patients. The recently discovered hormone ghrelin is a potent GH secretagogue with orexigenic and neuroprotective properties that may prevent or ameliorate these complications. The objective of this study was to determine the effects of ghrelin administration on mechanical hyperalgesia, anorexia, and cachexia induced by cisplatin. Adult male Sprague-Dawley rats were given cisplatin, ghrelin, ghrelin-cisplatin, or vehicle ip. Food intake and body weight were measured daily. Behavioral tests to assess the development of hyperalgesia were conducted by measuring mechanical and thermal sensitivity. Plasma ghrelin and IGF-I levels were also measured. Our results indicate that ghrelin coadministration inhibited the development of cisplatin-induced mechanical hyperalgesia, anorexia, and cachexia induced by cisplatin. Although ghrelin treatment had no effect on plasma IGF-I levels in control rats, it prevented the decrease in IGF-I levels induced by cisplatin. The attenuation of cisplatin-induced mechanical hyperalgesia induced by ghrelin was correlated with the prevention of cisplatin-induced lowering of IGF-I. In conclusion, ghrelin administration may be useful in the treatment or prevention of chemotherapy induced neuropathy and cachexia. Attenuation of mechanical hyperalgesia in the rat by the hormone ghrelin provides a unique model for elucidating the mechanisms involved, which are essential toward our understanding of these complications.

2005 ◽  
Vol 90 (6) ◽  
pp. 3337-3341 ◽  
Author(s):  
Susannah V. Rowles ◽  
L. Prieto ◽  
X. Badia ◽  
Steven M. Shalet ◽  
Susan M. Webb ◽  
...  

Acromegaly Quality of Life Questionnaire (AcroQoL) is a new disease-generated quality of life (QOL) questionnaire comprising 22 questions covering physical and psychological aspects of acromegaly and subdivided into “appearance” and “personal relations” categories. We have performed a cross-sectional study of QOL in 80 patients [43 male (mean age, 54.2 yr; range, 20–84); median GH, 0.93ng/ml (range, <0.3 to 23.7); IGF-I, 333.1 ng/ml (range, 47.7–899)] with acromegaly. In addition to AcroQoL, patients completed three generic QOL questionnaires: Psychological General Well-Being Schedule (PGWBS), EuroQol, and a signs and symptoms score (SSS). All three generic questionnaires confirmed impairment in QOL [mean scores: PGWBS, 69.6; EuroQol, visual analog scale, 66.4 (range, 20–100) and utility index, 0.7 (range, −0.07 to 0.92); and SSS, 12 (range, 0–27)]. There was no correlation between biochemical control and any measure of QOL. AcroQoL (57.3%; range, 18.2–93.2) correlated with PGWBS (r = 0.73; P < 0.0001); and in patients with active disease, AcroQoL-physical dimension correlated with SSS (r = −0.67; P < 0.0003). In all questionnaires, prior radiotherapy was associated with impaired QOL. In conclusion, these data underline the marked impact that acromegaly has on patients’ QOL and provide the first evidence validating AcroQoL against well-authenticated measures of QOL. This indicates the potential of AcroQoL as a patient-friendly measure of disease activity.


2015 ◽  
Vol 37 (3) ◽  
pp. 253-262 ◽  
Author(s):  
Susan B. Powell ◽  
Asma Khan ◽  
Jared W. Young ◽  
Christine N. Scott ◽  
Mahalah R. Buell ◽  
...  

Cognitive impairments appear early in the progression of schizophrenia, often preceding the symptoms of psychosis. Thus, the systems subserving these functions may be more vulnerable to, and mechanistically linked with, the initial pathology. Understanding the trajectory of behavioral and anatomical abnormalities relevant to the schizophrenia prodrome and their sensitivity to interventions in relevant models will be critical to identifying early therapeutic strategies. Isolation rearing of rats is an environmental perturbation that deprives rodents of social contact from weaning through adulthood and produces behavioral and neuronal abnormalities that mirror some pathophysiology associated with schizophrenia, e.g. frontal cortex abnormalities and prepulse inhibition (PPI) of startle deficits. Previously, we showed that PPI deficits in isolation-reared rats emerge in mid-adolescence (4 weeks after weaning; approx. postnatal day 52) but are not present when tested at 2 weeks after weaning (approx. postnatal day 38). Because cognitive deficits are reported during early adolescence, are relevant to the prodrome, and are linked to functional outcome, we examined the putative time course of reversal learning deficits in isolation-reared rats. Separate groups of male Sprague Dawley rats were tested in a two-choice discrimination task at 2 and 8 weeks after weaning, on postnatal day 38 and 80, respectively. The isolation-reared rats displayed impaired reversal learning at both time points. Isolation rearing was also associated with deficits in PPI at 4 and 10 weeks after weaning. The reversal learning deficits in the isolated rats were accompanied by reductions in parvalbumin immunoreactivity, a marker for specific subpopulations of GABAergic neurons, in the hippocampus. Hence, isolation rearing of rats may offer a unique model to examine the ontogeny of behavioral and neurobiological alterations that may be relevant to preclinical models of prodromal psychosis.


2008 ◽  
Vol 158 (3) ◽  
pp. 305-310 ◽  
Author(s):  
Maria P Matta ◽  
Elisabeth Couture ◽  
Laurent Cazals ◽  
Delphine Vezzosi ◽  
Antoine Bennet ◽  
...  

IntroductionAcromegaly, a chronic disease caused by GH/IGF-I excess, has a major impact on quality of life (QoL).ObjectiveTo evaluate QoL of acromegalic patients in relation to control status of the disease.Design and methodsSingle center observational study including 93 patients with acromegaly recruited to complete QoL questionnaire (AcroQol). QoL was evaluated at least 3 months after surgery and/or medical treatment. Patients were divided into two groups: controlled (I) and uncontrolled (II) according to the latest consensus acromegaly ‘control’ criteria and further subdivided into four subgroups according to the previous pituitary adenoma surgery (Ib and IIb) or without surgery (Ia and IIa).ResultsMean GH (0.81±0.47 ng/ml) and IGF-I (195±71 ng/ml) values in group I were significantly lower than in group II (GH, 7.01±12.05 ng/ml and IGF-I, 513±316 ng/ml; P<0.001). There was no difference in total AcroQol score, physical, or psychological scales between groups I and II. However, when adjusted to age and disease duration since diagnosis, patients of group I (63±20%) showed an improved psychological subscale appearance than those of group II (58±17%; P=0.035). In group II, IGF-I level was lower after surgery (IIa=588±353, IIb=410±225 ng/ml; P<0.038), and psychological subscale appearance was significantly better in subgroup IIb (64.9±18.1%) than in subgroup IIa who had medical treatment (53.9±14.3%; P=0.009).ConclusionQoL is severely impaired in acromegalic patients. Control of GH/IGF-I excess by surgery or medical treatment seems to have a positive impact on psychological subscale appearance.


2018 ◽  
Author(s):  
Ricardo Siu ◽  
James J Abbas ◽  
Brian K Hillen ◽  
Jefferson Gomes ◽  
Stefany Coxe ◽  
...  

Ventilatory pacing via electrical stimulation of the phrenic nerve or of the diaphragm has been shown to enhance quality of life compared to mechanical ventilation. However, commercially-available ventilatory pacing devices require initial manual specification of stimulation parameters and frequent adjustment to achieve and maintain suitable ventilation over long periods of time. Here, we have developed an adaptive, closed-loop, neuromorphic, pattern-shaping controller capable of automatically determining a suitable stimulation pattern and adapting it to maintain a desired breath volume profile on a breath-by-breath basis. In vivo studies in anesthetized intact and C2-hemisected male Sprague-Dawley rats indicated that the controller was capable of automatically adapting stimulation parameters to attain a desired volume profile. Despite diaphragm hemiparesis, the controller was able to achieve a desired volume in the injured animals that did not differ from the tidal volume observed prior to injury (p=0.39). The closed-loop controller was developed and parametrized in a computational testbed prior to in-vivo assessment. This bioelectronic technology could serve as an individualized and autonomous respiratory pacing approach for support or recovery from ventilatory deficiency.


2021 ◽  
Vol 18 (6) ◽  
pp. 1219-1225
Author(s):  
Farah Dayana Rosli ◽  
Noor Hashida Hashim ◽  
Yusmin Mohd Yusuf ◽  
Khairul Osman ◽  
Siti Fatimah Ibrahim ◽  
...  

Purpose: To assess the effects of thymoquinone (TQ) on the integrity of sperm DNA in nicotineinduced sperm impairment in rats. Methods: Adult male Sprague Dawley rats were randomized into four equal groups: control group received normal saline orally for 60 days; nicotine group was subcutaneously injected with 5 mg/kg/day nicotine for 30 days and then given normal saline for the next 30 days; TQ group was given normal saline for 30 days followed by TQ at 5 mg/kg/day for 30 days; and nicotine-TQ group received 5 mg/kg of nicotine for 30 days and 5mg/kg of TQ for another 30 days. Sperm DNA breakages were evaluated using Comet assay. The expression levels of protamine 1 (PT1) and transition nuclear protein 2 (Tnp2) genes which are essential for the proper compaction of the sperm DNA were analyzed by quantitative polymerase chain reaction (qPCR). Results: Thymoquinone significantly decreased DNA fragmentation in the sperm of nicotine-treated rats. However, there was no change in PT1 gene expression. Tnp2 was downregulated in the nicotine group and slightly upregulated in nicotine-TQ group (p < 0.05). Conclusion: The results demonstrate the potential benefits of TQ in improving sperm DNA quality of nicotine-induced male infertility.


2016 ◽  
Author(s):  
Stephen Shalet ◽  
Peter Jonsson ◽  
Andreas Pleil ◽  
Cecilia Camacho-Hubner ◽  
Roger Abs
Keyword(s):  

2021 ◽  
Vol 15 ◽  
Author(s):  
Han Qiu ◽  
Tianyang Qian ◽  
Tong Wu ◽  
Ting Gao ◽  
Qinghe Xing ◽  
...  

Hypoxic-ischemic (HI) injury is one of the initial factors contributing to neonatal brain injury. Src family kinases (SFKs) are considered to act as molecular hubs for N-methyl-d-aspartate receptor (NMDAR) regulation and participate in the HI injury process. The objectives of this study were to evaluate the levels of phospho-Src (p-Src), the relationship between NMDARs and SFKs, and the effects of SFK inhibition on an immature rat HI brain injury model. The model was induced in 3-day-old Sprague–Dawley rats using the Rice-Vannucci model operation. The level of p-Src was evaluated using Western blotting. The association of NMDARs with SFKs was detected using Western blotting and coimmunoprecipitation. After intraperitoneal injection of 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo [3,4-d] pyrimidine (PP2), an SFK-selective inhibitor, neuropathological changes were observed by performing H&amp;E and immunofluorescence staining, and the neurological functions were assessed using the following behavioral tests: modified neurological severity score, open field test, and Morris water maze test. The levels of p-Src first decreased at 0 h after injury, increased at 2 h after injury, and continuously decreased from 6 h to 3 days. Along with the increased p-Src levels observed at 2 h after injury, the phosphorylation of NMDAR subunit NR2B at tyrosine 1472 was increased. Following the administration of PP2, the increased p-Src and NMDAR-2B levels detected at 2 h after injury were decreased, and tissue injury and myelin basic protein expression were improved at 7 days after injury. The PP2 intervention improved the performance of injured rats on behavioral tests. In conclusion, we determined the patterns of p-Src expression after HI brain injury in immature rats and showed a relationship with the activated NMDA receptor. The inhibition of p-Src ameliorates neuropathological changes and damages neurological functions induced by HI injury.


2013 ◽  
Vol 98 (2) ◽  
pp. 761-768 ◽  
Author(s):  
Aimee J. Varewijck ◽  
Steven W. J. Lamberts ◽  
Sebastian J. C. M. M. Neggers ◽  
Leo J. Hofland ◽  
Joseph A. M. J. L. Janssen
Keyword(s):  

2015 ◽  
Vol 20 (2) ◽  
pp. 112-116 ◽  
Author(s):  
Mina Park ◽  
Ho Sun Lee ◽  
Jun-Jae Choi ◽  
Hyeonjin Kim ◽  
Jun Ho Lee ◽  
...  

Objective: To compare the quality of perilymphatic enhancement in the rat inner ear after intratympanic injection of two types of gadolinium with a 9.4-tesla micro-MRI. Materials and Methods: Gadolinium was injected into the middle ear in 6 Sprague-Dawley rats via the transtympanic route. The left ear was injected with Gd-DO3A-butrol first, and then the right ear was injected with Gd-DOTA. MR images of the inner ear were acquired 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4 h after intratympanic (IT) injection using an Agilent MRI system 9.4T/160/AS. The normalized signal intensity was quantitatively analyzed at the scala vestibuli (SV), scala media, and scala tympani (ST) using a Marosis M-view system. Then the normalized signal intensities (SIs) were compared between the two contrast agents. Results: For Gd-DO3A-butrol, the SI was as low as 1.0-1.5 throughout 1-4 h at the SV and ST of the basal turn. The maximum SI was 1.5 ± 0.5 at the SV (2 h) and 1.3 ± 0.5 at the ST (2 h). For Gd-DOTA, the 1-hour postinjection SI at the basal turn was 2.5 ± 0.5 at the SV, 1.6 ± 0.3 at the ST, and 1.2 ± 0.3 at the scala media. In the apical turn, the maximum SI was reached after 2.5 h. The maximum SI in the apical turn was 1.8 ± 0.4 at the SV (3.5 h), 1.8 ± 0.4 at the ST (4 h), and 1.4 ± 0.3 at the scala media (4 h). Conclusions: We were able to clearly visualize and separate the ST and SV using IT Gd and 9.4-tesla micro-MRI. We recommend using Gd-DO3A-butrol over Gd-DOTA and to perform the MRI 2.5 h after using IT Gd in the rat inner ear.


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