Amplification of pulsatile glucagon counterregulation by switch-off of α-cell-suppressing signals in streptozotocin-treated rats

Glucagon counterregulation (GCR) is a key protection against hypoglycemia that is compromised in diabetes via an unknown mechanism. To test the hypothesis that α-cell-inhibiting signals that are switched off during hypoglycemia amplify GCR, we studied streptozotocin (STZ)-treated male Wistar rats and estimated the effect on GCR of intrapancreatic infusion and termination during hypoglycemia of saline, insulin, and somatostatin. Times 10 min before and 45 min after the switch-off were analyzed. Insulin and somatostatin, but not saline, switch-off significantly increased the glucagon levels ( P = 0.03), and the fold increases relative to baseline were significantly higher ( P < 0.05) in the insulin and somatostatin groups vs. the saline group. The peak concentrations were also higher in the insulin (368 pg/ml) and somatostatin (228 pg/ml) groups vs. the saline (114 pg/ml) group ( P < 0.05). GCR was pulsatile in most animals, indicating a feedback regulation. After the switch-off, the number of secretory events and the total pulsatile production were lower in the saline group vs. the insulin and somatostatin groups ( P < 0.05), indicating enhancement of glucagon pulsatile activity by insulin and somatostatin compared with saline. Network modeling analysis demonstrates that reciprocal interactions between α- and δ-cells can explain the amplification by interpreting the GCR as a rebound response to the switch-off. The model justifies experimental designs to further study the intrapancreatic network in relation to the switch-off phenomenon. The results of this proof-of-concept interdisciplinary study support the hypothesis that GCR develops as a rebound pulsatile response of the intrapancreatic endocrine feedback network to switch-off of α-cell-inhibiting islet signals.

Download Full-text

Genotoxic and mutagenic effects of vigabatrin, a γ-aminobutyric acid transaminase inhibitor, in Wistar rats submitted to rotarod task

Human & Experimental Toxicology ◽

10.1177/0960327115611970 ◽

2016 ◽

Vol 35 (9) ◽

pp. 958-965 ◽

Cited By ~ 5

Author(s):

VR Coelho ◽

K Sousa ◽

TR Pires ◽

DKM Papke ◽

CG Vieira ◽

...

Keyword(s):

Acute Treatment ◽

Wistar Rats ◽

Micronucleus Test ◽

Repeated Administration ◽

Saline Group ◽

Aminobutyric Acid ◽

Subchronic Treatment ◽

Motor Activities ◽

Male Wistar Rats ◽

Mutagenic Effects

Vigabatrin (VGB) is an antiepileptic drug thatincreases brain γ-aminobutyric acid (GABA) levels through irreversible inhibition of GABA transaminase. The aim of this study was to evaluate neurotoxicological effects of VGB measuring motor activity and genotoxic and mutagenic effects after a single and repeated administration. Male Wistar rats received saline, VGB 50, 100, or 250 mg/kg by gavage for acute and subchronic (14 days) treatments and evaluated in the rotarod task. Genotoxicity was evaluated using the alkaline version of the comet assay in samples of blood, liver, hippocampus, and brain cortex after both treatments. Mutagenicity was evaluated using the micronucleus test in bone marrow of the same animals that received subchronic treatment. The groups treated with VGB showed similar performance in rotarod compared with the saline group. Regarding the acute treatment, it was observed that only higher VGB doses induced DNA damage in blood and hippocampus. After the subchronic treatment, VGB did not show genotoxic or mutagenic effects. In brief, VGB did not impair motor activities in rats after acute and subchronic treatments. It showed a repairable genotoxic potential in the central nervous system since genotoxicity was observed in the acute treatment group.

Download Full-text

Influence of preoperative supplementation of omega-3 fatty acid in the healing of colonic anastomoses in malnourished rats receiving paclitaxel

Revista do Colégio Brasileiro de Cirurgiões ◽

10.1590/0100-69912015002009 ◽

2015 ◽

Vol 42 (2) ◽

pp. 116-123 ◽

Cited By ~ 3

Author(s):

Alvo Orlando Vizzotto Junior ◽

Antonio Carlos Ligocki Campos ◽

Eneri Vieira de Souza Leite Mello ◽

Tiago Jacometo Castilho

Keyword(s):

Fatty Acids ◽

Rupture Strength ◽

Saline Group ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Colonic Anastomoses ◽

Omega 3 Fatty Acid ◽

Paclitaxel Group ◽

Male Wistar Rats ◽

Maturation Index

OBJECTIVE: To evaluate the effect of preoperative supplementation of omega-3 fatty acids on the healing of colonic anastomoses in malnourished rats receiving paclitaxel. METHODS: we studied 160 male Wistar rats, divided in two groups: one subjected to malnutrition by pair feeding (M) for four weeks, and another that received food ad libitum (W). In the fourth week, the groups were further divided into two subgroups that received omega-3 or olive oil by gavage. The animals were submitted to colonic transection and end-to-end anastomosis. After the operation, each of the four groups was divided into two subgroups that received intraperitoneal isovolumetric solutions of saline or paclitaxel. RESULTS: mortality was 26.8% higher in the group of animals that received paclitaxel (p = 0.003). The complete rupture strength was greater in well-nourished-oil Paclitaxel group (WOP) compared with the the malnourished-oil Paclitaxel one (MOP). The collagen maturation index was higher in well-nourished-oil saline group (WOS) in relation to the malnutrition-oil-saline group (MOS), lower in malnourished-oil-saline group (MOS) in relation to malnourished-ômega3-saline one (M3S) and lower in the well-nourished-omega3-saline group (W3S) compared with the malnourished-omega3-saline (M3S). The blood vessel count was higher in the malnourished-oil-saline group (MOS) than in the malnourished-oil-paclitaxel group (MOP) and lower in the malnourished-oil-saline group (MOS) in relation to the malnourished-omega3-paclitaxel group (M3P). CONCLUSION: supplementation with omega-3 fatty acids was associated with a significant increase in the production of mature collagen in malnourished animals, with a reversal of the harmful effects caused by malnutrition associated with the use of paclitaxel on the rupture strength, and with a stimulus to neoangiogenesis in the group receiving paclitaxel.

Download Full-text

Auditory Profile-based Hearing-aid Fitting: A Proof-Of-Concept Study

10.1101/2020.04.14.20036459 ◽

2020 ◽

Author(s):

Raul Sanchez-Lopez ◽

Michal Fereczkowski ◽

Sébastien Santurette ◽

Torsten Dau ◽

Tobias Neher

Keyword(s):

Hearing Aids ◽

Hearing Aid ◽

Data Driven ◽

Proof Of Concept ◽

Hearing Aid Fitting ◽

Concept Study ◽

Pure Tone Audiogram ◽

Comprehensive Test ◽

Study Support

AbstractObjectiveThe clinical characterization of hearing deficits for hearing-aid fitting purposes is typically based on the pure-tone audiogram only. In a previous study, a group of hearing-impaired listeners were tested using a comprehensive test battery designed to tap into different aspects of hearing. A data-driven analysis of the data yielded four clinically relevant patient subpopulations or “auditory profiles”. In the current study, profile-based hearing-aid settings were proposed and evaluated to explore their potential for providing more targeted hearing-aid treatment.DesignFour candidate hearing-aid settings were implemented and evaluated by a subset of the participants tested previously. The evaluation consisted of multi-comparison preference ratings carried out in realistic sound scenarios.ResultsListeners belonging to the different auditory profiles showed different patterns of preference for the tested hearing-aid settings that were largely consistent with the expectations.ConclusionThe results of this proof-of-concept study support further investigations into stratified, profile-based hearing-aid fitting with wearable hearing aids.

Download Full-text

Treatment of traumatic brain injury with thymosin β4 in rats

Journal of Neurosurgery ◽

10.3171/2010.4.jns10118 ◽

2011 ◽

Vol 114 (1) ◽

pp. 102-115 ◽

Cited By ~ 57

Author(s):

Ye Xiong ◽

Asim Mahmood ◽

Yuling Meng ◽

Yanlu Zhang ◽

Zheng Gang Zhang ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Sham Group ◽

Therapeutic Potential ◽

Cell Loss ◽

Saline Group ◽

Lesion Volume ◽

Male Wistar Rats ◽

Left Parietal Cortex ◽

First Time

Object This study was designed to investigate the efficacy of delayed thymosin β4 (Tβ4) treatment of traumatic brain injury (TBI) in rats. Methods Young adult male Wistar rats were divided into the following groups: 1) sham group (6 rats); 2) TBI + saline group (9 rats); 3) and TBI + Tβ4 group (10 rats). Traumatic brain injury was induced by controlled cortical impact over the left parietal cortex. Thymosin β4 (6 mg/kg) or saline was administered intraperitoneally starting at Day 1 and then every 3 days for an additional 4 doses. Neurological function was assessed using a modified neurological severity score (mNSS), foot fault, and Morris water maze tests. Animals were killed 35 days after injury, and brain sections were stained for immunohistochemistry to assess angiogenesis, neurogenesis, and oligodendrogenesis after Tβ4 treatment. Results Compared with the saline treatment, delayed Tβ4 treatment did not affect lesion volume but significantly reduced hippocampal cell loss, enhanced angiogenesis and neurogenesis in the injured cortex and hippocampus, increased oligodendrogenesis in the CA3 region, and significantly improved sensorimotor functional recovery and spatial learning. Conclusions These data for the first time demonstrate that delayed administration of Tβ4 significantly improves histological and functional outcomes in rats with TBI, indicating that Tβ4 has considerable therapeutic potential for patients with TBI.

Download Full-text

K-core analysis and modeling for network centralities

International Journal of Engineering & Technology ◽

10.14419/ijet.v7i2.7.10285 ◽

2018 ◽

Vol 7 (2.7) ◽

pp. 168

Author(s):

V MNSSVKR Gupta ◽

Ch V.Phani Krishna

Keyword(s):

Network Modeling ◽

Network Graph ◽

Frequency Limit ◽

Cloud Data ◽

Undirected Network ◽

Word Cloud ◽

Interdisciplinary Study ◽

Network Centralities ◽

Word Frequencies ◽

Different Levels

Network modeling is the interdisciplinary study of relationships. Network analysis deals with relational data and Network modeling represents the interdisciplinary study of relationships. Network structure can be studied at many different levels. Around 1000 article titles on cancer, published in journal resources were considered as a dataset. Data exploration was done through displaying nodes and edges in various layouts. With a term frequency limit of 100, nearly 64 terms appeared which less than 1% sparse is. Word cloud data was plotted using word frequencies from term matrix data. An undirected network graph plotted and evaluated density, average path length and modularity, which were found to be within limits. K-cores have also been used to analyze the connectivity of a network. Network centralities such as Degree centrality, Closeness, Eigenvector and between’s centrality resulted in node carcinoma being more central in the network.

Download Full-text

Blockade of prelimbic glutamate receptor reduces the reinforcing effect of morphine

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2017-0758 ◽

2018 ◽

Vol 96 (8) ◽

pp. 815-822 ◽

Cited By ~ 2

Author(s):

Fateme Aboutalebi ◽

Hojjatallah Alaei ◽

Shahrbanoo Oryan ◽

Maryam Radahmadi

Keyword(s):

Ampa Receptors ◽

Nmda Antagonist ◽

Saline Group ◽

Glutamatergic Transmission ◽

Self Administration ◽

Morphine Group ◽

Active Lever ◽

Male Wistar Rats ◽

Lever Pressing ◽

Different Doses

The prelimbic cortex (PrL) as a part of the medial prefrontal cortex (mPFC) plays a crucial role in drug addiction. Previous studies have shown that glutamatergic transmission through the NMDA and AMPA receptors plays an important role in morphine rewarding properties. In this study, we evaluated the effect of glutamate receptors blockade within the PrL on morphine self-administration. Male Wistar rats were randomly selected and divided into 7 groups. Trained rats were placed in self-administration apparatus, where they pressed an active lever for receiving morphine (5 mg/mL) in test groups and saline in saline group during 11 consecutive days for 2 h per session. The effects of intra-prelimbic AMPA receptor antagonist (CNQX; 0.5 and 2.5 μg/0.5 μL) and the NMDA antagonist (AP5; 0.1 and 1 μg/0.5 μL) on self-administration were tested. Our results demonstrated that intra-prelimbic injection of different doses of CNQX and AP5, and co-administration of these 2 drugs before self-administration significantly decreased active lever pressing compared with morphine group (p < 0.001). Also, the number of self-infusion significantly decreased in test groups compared with morphine group (p < 0.001). These findings suggest that a reduction in PrL glutamatergic output can modulate morphine reinforcement.

Download Full-text

Antimalarial combination therapies increase gastric ulcers through an imbalance of basic antioxidative-oxidative enzymes in male Wistar rats

10.21203/rs.2.22004/v1 ◽

2020 ◽

Author(s):

Muhamudu Kalange ◽

Miriam Nansunga ◽

Keneth Iceland Kasozi ◽

Josephine Kasolo ◽

Jackline Namuleme ◽

...

Keyword(s):

Gastric Mucosa ◽

Wistar Rats ◽

Saline Group ◽

Positive Control ◽

Negative Control ◽

Oxidative Enzymes ◽

Gastric Ulcers ◽

Combination Therapies ◽

Male Wistar Rats ◽

High Gastric Ulcer

Abstract Objective: Antimalarials are globally used against plasmodium infections, however, information on the safety of new antimalarial combination therapies on the gastric mucosa is scarce. The aim of the study was to establish the effects of Artesunate-Amodiaquine and Artemether-Lumefantrine on gastric ulcers, malondialdehyde (MDA), reduced glutathione (GSH) and identify major histological changes in male Wistar rats. Gastric ulcers were induced using Indomethacin in four groups and group 1 was administered Artesunate, group 2 received Artesunate-Amodiaquine, group 3 received Artemether-Lumefantrine, and group 4 was a positive control (normal saline). Group five was the negative control consisting of healthy rats. Results: Antimalarial combination therapies were associated with a high gastric ulcer index than a single antimalarial agent, Artesunate. In addition, levels of MDA were significantly higher in the combination of therapies while levels of GSH were lower in comparison to Artesunate and the negative control. Microscopically, antimalarial combination therapies were associated with severe inflammation and tissue damage than Artesunate in the gastric mucosa showing that antimalarial combination therapies exert their toxic effects through oxidative stress mechanisms, and this leads to apoptosis. Findings in this study demonstrate a new to revisit information on the pharmacodynamics of major circulating antimalarial agents in developing countries.

Download Full-text

Study on antihyperglycemic effect of bromocriptine in dexamethasone induced hyperglycemic wistar rats

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20212081 ◽

2021 ◽

Vol 10 (6) ◽

pp. 699

Author(s):

Rekha M. B. ◽

Basavaraj Bhandare ◽

Satyanarayana V. ◽

Hemamalini M. B.

Keyword(s):

Diabetes Mellitus ◽

Normal Saline ◽

Wistar Rats ◽

Saline Group ◽

Control Group ◽

Normal Saline Group ◽

Male Wistar Rats ◽

Group B ◽

Control Group Group

Background: Diabetes mellitus is a chronic metabolic disorder that develops due to insulin deficiency or insulin resistance. Recent animal and human studies have reported bromocriptine to be effective in the management of type 2 diabetes mellitus. The present study was done to evaluate the antihyperglycemic effect of bromocriptine in dexamethasone induced hyperglycemic rats.Methods: Male wistar rats were used and divided into 5 groups. Dexamethosone was used to induce hyperglycemia in group B-E. Group A was the untreated control group, group B was the standard control group, group C was the oral 10 mg/kg of bromocriptine dissolved in 0.9% normal saline, group D was the oral 20 mg/kg metformin dissolved in 0.9% normal saline, group E was the oral 10 mg/kg bromocriptine+20 mg/kg metformin dissolved in 0.9% normal saline. Fasting blood glucose, post prandial blood glucose and body weight was estimated on day 1, 15, 30.Results: It was seen that dexamethasone induced hyperglycemia and increase in body weight in male wistar rats, which were significantly controlled by oral bromocriptine and bromocriptine with metformin combination.Conclusions: Results obtained from this study showed that bromocriptine can be a promising drug with novel mechanism to treat type 2 diabetes mellitus.

Download Full-text

Is there a therapeutic window for pentoxifylline after the onset of acute pancreatitis?

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502012000700010 ◽

2012 ◽

Vol 27 (7) ◽

pp. 487-493 ◽

Cited By ~ 4

Author(s):

Ana Maria Mendonça Coelho ◽

Tiago Alexandre Kunitake ◽

Marcel Cerqueira Cesar Machado ◽

Joilson Oliveira Martins ◽

Rosely Antunes Patzina ◽

...

Keyword(s):

Acute Pancreatitis ◽

Saline Solution ◽

Serum Levels ◽

Saline Group ◽

Therapeutic Window ◽

Enzyme Linked Immunosorbent Assay ◽

Myeloperoxidase Activity ◽

Tnf Α ◽

Male Wistar Rats ◽

Necrosis Factor

PURPOSE: To investigate the effects of pentoxifylline (PTX) in experimental acute pancreatitis (AP) starting drug administration after the induction of the disease. METHODS: One hundred male Wistar rats were submitted to taurocholate-induced AP and divided into three groups: Group Sham: sham-operated rats, Group Saline: AP plus saline solution, and Group PTX: AP plus PTX. Saline solution and PTX were administered 1 hour after induction of AP. At 3 hours after AP induction, peritoneal levels of tumor necrosis factor (TNF)-α, and serum levels of interleukin (IL)-6 and IL-10 levels were assayed by Enzyme-Linked Immunosorbent Assay (ELISA). Determinations of lung myeloperoxidase activity (MPO), histological analysis of lung and pancreas, and mortality study were performed. RESULTS: PTX administration 1 hour after induction of AP caused a significant decrease in peritoneal levels of TNF-α and in serum levels of IL-6 and IL-10 when compared to the saline group. There were no differences in lung MPO activity between the two groups with AP. A decrease in mortality was observed in the PTX treatment compared to the saline group. CONCLUSIONS: Administration of PTX after the onset of AP decreased the systemic levels of proinflammatory cytokines, raising the possibility that there is an early therapeutic window for PTX after the initiation of AP.

Download Full-text

Moderate-intensity interval training (MIT) can protect rats against Methamphetamine –induced injuries

10.21203/rs.3.rs-1021997/v1 ◽

2021 ◽

Author(s):

Ahad Shafiei Bafti ◽

Amir Hossein Haghighi ◽

Roya Askari ◽

Alireza Keyhani ◽

Mahla sadat Nabavi Zadeh ◽

...

Keyword(s):

Gene Expression ◽

Antioxidant Enzymes ◽

Spatial Memory ◽

Interval Training ◽

Saline Group ◽

Neural System ◽

Male Rats ◽

Moderate Intensity ◽

Morris Water Maze Test ◽

Male Wistar Rats

Abstract Methamphetamine (METH) can cause neurotoxicity and increase the risk of neurodegenerative disorders such as Alzheimer disease and Parkinson disease. This study aimed to investigate the effect of moderate-intensity interval training (MIT) on gene expression and antioxidant status of the hippocampus of METH-dependent rats. Twenty-eight male Wistar rats were randomly divided into four equal groups (n=7): saline, METH, MIT, and METH+MIT. METH was injected intraperitoneally at 5 mg/kg for 21 days. The MIT (intermittent running) was performed on the treadmill 5 days a week for 8 weeks. Morris Water Maze test was performed to measure learning and memory. Then, the hippocampal tissue was extracted to evaluate changes in gene expression and biochemical enzymes. The data were analyzed using one-way and two-way ANOVA methods at P<0.05. The results showed that METH injection significantly reduced spatial memory and antioxidant enzymes and increased the expression of α-synuclein (α-syn), cyclin-dependent kinase 5 (CDK5), tau and phosphorylated tau (p-Tau) genes compared to the saline group. MIT significantly increased spatial memory and antioxidant enzymes. However, it reduced α-syn, CDK5, tau and p-tau expression. Thus, METH caused neural damage, and MIT could protect the neural system against METH-induced insults in male rats.

Download Full-text