Physiology and Pharmacology
Volume:27 Issue: 3, Sep 2023

Glucocorticoids are widely employed for treating various disorders, but their administration is associated with multiple adverse effects. To study and understand these side effects, preclinical animal models have been developed. Experimental models that replicate essential aspects of human diseases offer valuable tools for assessing potential therapeutic agents and elucidating molecular and cellular pathways in a controlled environment. In this review, we provide an overview of various animal models in which glucocorticoids have been utilized to induce humanlike disorders across different body systems. These disorders encompass hypertension, skin atrophy, hair loss, insulin resistance, dyslipidemia, gastric mucosal damage, growth retardation, muscle atrophy, osteoporosis, osteonecrosis, depression-like behavior, glaucoma, and cataracts.

TThe term “Smart hospital” is a highly comprehensive concept and it has not received the attention it deserves among researchers, as it is more than using a smart tool in a hospital. This study was designed to conduct a review of smart hospitals. In this systematic review, 808 studies were identified using keywords through searches on PubMed, Science Direct, Embase, Scopus and IEEE databases. After applying the inclusion and exclusion criteria (705 based on abstracts and titles and 35 after reading full texts) and removing duplicates (43), 25 studies were included in this review. Geographically, of the majority of the articles were from Asia (60%). The highest number of publications was observed in 2012 and 2020. A multidisciplinary team was involved in 72% of the research, and 68% were conducted in more than one research center. Most articles have been published in Q1 quality journals (48%), and high-income countries accounted for the largest percentage (56). Notably, 32% of these studies focused on patient care. RFID technology was the most used technology, featured in 66.67% of the studies, which primarily centered on the implementation of smart hospitals. It should be noted that development or implementation of a smart device in a hospital should not be equated with the implementation of a smart hospital and it is far beyond that.

Light-dark cycles regulate the body’s physiological activity; hence, marked changes in these cycles could lead to conditions with impaired brain functions and disrupted moods (e.g., stress). Therefore, this study compared the impact of stress due to various photoperiodic durations on anxiety-like behavior, learning, memory, locomotor activity and memory consolidation in rats.

Thirty-five male rats were divided into five groups with different light(L)-dark(D) cycles: L20/D4, L16/D8, L12/D12 (control), L8/D16 and L4/D20 groups. After14 days, the elevated plus-maze (EPM) and passive avoidance (PA) tests were performed to assess the anxiety-like behaviors and brain functions.

The percentage of spent time, number of entries to the open arm of the EPM test and the entrance latency to the dark room of the PA test decreased significantly in the L20/D4 and L4/D20 groups; however, the reduction of latency to enter the dark room was particularly significant in the L20/D4 group. In addition, there were significant differences between the initial latency and latency after one day (as learning) in all experimental groups. The total dark stay time increased significantly in different photoperiods.

An abnormal light-dark length could disrupt certain brain functions, such as learning, memory, locomotor activity, memory consolidation and anxiety-like behavioral responses at different levels in a time-independent manner. The light-dark length (both minimum and especially the maximum day length) led to increased learning impairment and memory deficits, as well as worsened anxiety-like behaviors. The memory consolidation was also disrupted with various photoperiods.

Preeclampsia is the principal cause of maternal morbidity and is characterized by hypertension, proteinuria, and edema. It is believed that oxidative stress plays an essential role in the pathophysiology of preeclampsia. This study was conducted to determine the effect of tempol on fetal limb hemorrhage, malformations, and oxidative stress in an N-nitro-L-arginine methyl ester (L-NAME)-induced preeclamptic rat model.

To induce preeclampsia, L-NAME (50 mg/kg/day, oral) was administered from day 11 of pregnancy to day 22. Four preeclamptic groups received L-NAME alone, L-NAME+tempol (20, 60, 180 mg/kg/day; L-NAME, L-T20, L-T60, L-T180 groups, respectively). The control group (normal pregnant) received only tap water, and the T60 group received tempol (60 mg/Kg) alone (without L-NAME). The concentration of 8-isoprostane in plasma and placenta, number and weight of the fetuses, and the limb defects were measured on the 22nd day of the pregnancy.

L-NAME administration caused placental oxidative stress, limb defects and hemorrhage, and low fetal weight. Administration of tempol at 20 and 60 mg/kg/day reduced limb defects (10.5 and 7.2 percent versus 24.7 percent) and limb hemorrhage (14.5 and 9.5 percent versus 23 percent) induced by L-NAME. After administration of tempol (20 and 60 mg/kg), fetal weight increased (5.14±0.08 and 5.44±0.15 versus 4.27± 0.11 g). Administration of tempol at the high dose (180 mg/kg/day) did not produce any significant effects on the measured parameters.

Tempol with certain doses improves fetal outcomes in an experimental rat model of preeclampsia. These may be the results of its antioxidant action.

We investigated the subchronic toxicity concerns of a polyherbal formulation (PHF; Dr Iguedo Goko Cleanser®) on haematological indices, brain and spleen histomorphology in exposed Wistar rats of both sexes.

Thirty Wistar rats randomly allotted to six groups (5/group) were experimentally exposed to PHF via the oral route for 60 days as follows: control groups (1 and 4; given 5ml/kg distilled water); groups 2, 5 (476.24mg/kg) and 3, 6 (158.75mg/kg) body weight PHF, respectively. On 62nd day, animals were euthanized using carbon dioxide and sacrificed; spleen and brain tissues were evis-cerated, weighed and fixed in 10% buffered-formalin for histopathological assessment.

Our results showed significant increase in platelet in all experimental rats relative to control. Low dosed (158.75mg/kg) male rats recorded a significant increase in WBC relative to control. Also increased were MCV and MCH in male rats. High dosed female rats had increased RBC and MCV. Neutrophils and lymphocyte differentials were respectively decreased and increased in experimental groups relative to control. Histopathology of the spleen and brain tissues revealed degrees of pathologies like abnormal cytostructure of lymphoid follicle, degenerated T-lymphocytes, numerous organic deposits, degenerating neural cells, proliferating astrocytes, widely scattered blood vessel amongst others.

Our findings revealed exposure-associated toxic effects of the quasi-drug formulation on blood parameters and histostructure of the spleen and brain. Findings suggest utmost caution on long-term use of the polyherbal formulation and avoidance whenever possible.

Ganoderma lucidum (G. lucidum), a medicinal mushroom, exerts protective effects on cardiovascular diseases but, it’s effect in isoproterenol-induced heart failure has not been studied. Therefore, the aim of the present study was whether G. lucidum has protective effects in isoproterenol-induced heart failure.

Thirty male Wistar rats were assigned into five groups (n=6) of control, heart failure (HF) and G. lucidum (50, 100 and 200mg/kg). For induction of HF in rats, isoproterenol (5mg/ kg) was injected subcutaneously for two weeks. In G. lucidum treated groups, G. lucidum was orally gavaged for three weeks and on day 8 isoproterenol was injected for two weeks. Then, Electrocardiogram pattern and cardiodynamic parameters, as well as myeloperoxidase activity, malondialdehyde level, cardiac remodeling and apoptosis were studied.

G. lucidum improved hemodynamic factors such as mean arterial blood pressure as well as electrocardiogram pattern. Pre-treatment with G. lucidum also decreased myeloperoxidase activity, malondialdehyde level and apoptosis in cardiac tissue. Histopathologic results showed a decrease in cardiac necrosis and fibrosis. However, it had no significant effect on cardiac hypertrophy.

Our results show that pre-treatment with G. lucidum demonstrates protective effects against HF, and thereby suggest that G. lucidum can be considered as a possible clinical use for preventive and adjuvant treatment in heart failure.

The molecular mechanism of idiopathic antibiotic-associated diarrhea is not clear. Сeftriaxone, a third-generation cephalosporin, is a broad-spectrum antibiotic and diarrhea is the main side-effect of ceftriaxone treatment. The present study tested the hypothesis that ceftriaxone-induced diarrhea is associated with a shift in microbiota composition followed by the alteration in colonic water/ion transport, the expression pattern of transporters and epithelial barrier function.

Male Wistar rats were treated daily with ceftriaxone (50 mg/kg, i.m.) for 5 or 14 days. Epithelial net water and ion transport (Na+ , K+ , Cl- ) were evaluated on the 6th or 15th day respectively by isolated colonic loop perfusion technique in vivo. Gene expression by RT-PCR, glycoproteins levels by PAS-staining, and microbiota by culture method on the elective medium were evaluated.

Decreases in Na+ and water absorption, surface mucus layer, and Scnn1b and Aqp8 gene expression were associated with more severe diarrhea after 5 days-antibiotic treatment. After 14-days of antibiotic treatment, fewer animals with diarrhea were observed. At the same time, there was a decrease of Cl- and an increase in Na+ absorption, along with increased mucus secretion and upregulation of Cftr, Scnn1b, Slc9a3, Muc2, Ocln, and Tjp1 gene expression. These changes were accompanied by an increase in the number of culturable conditionally pathogenic microbiota after 5 days of treatment which almost returned to the control value after 14 days of treatment.

We concluded that the observed transitory antibiotic-associated diarrhea was a well-orchestrated physiological defense response at the molecular level driven by the shift in normal microbiota composition.

Tacca chantrieri Andre is frequently used by traditional healers to alleviate pain and fever, primirily by reducing inflammation. Its rhizome extract possesses remarkable peripheral anti-inflammatory and antioxidant bioactivities. However, there is limited information available regarding its potential anti-neuroinflammation effects. This study aimes to assess the neuroprotective effects of T. chantrieri rhizome ethanol extract (TCE) against lipopolysaccharides (LPS)-induced neuroinflammation.

Rats were orally administered with TCE at doses of 50, 100, and 200 mg/kg continually for 9 days. On the 7th day of treatment, each rat received a single intraperitoneal injection of LPS (0.83 mg/kg). Cognitive performance was assessed using the Y-maze test and novel object recognition (NOR) test. Thereafter, the proinflammatory cytokine level in the hippocampus was measured by ELISA.

Systemic LPS administration induced sickness behavior, cognitive impairment, and neuroinflammation. TCE at doses of 100 and 200 mg/kg reversed the LPS-induced behavioral deficits, showing improvements in spontaneous alternation in the Y-maze test and discrimination index in the NOR test. Additionally, pretreatment with TCE at doses of 100 and 200 mg/kg significantly attenuated the LPS-induced increase in protein expression of TNF-α.

TCE exhibited neuroprotective effects against LPS-induced cognitive deficits and suppressed the production of pro-inflammatory mediators in a dose-dependent manner. These findings indicate that TCE may hold therapeutic potential in preventing neuroinflammation associated cognitive impairment. However, further studies are necessary to validate the possible mechanisms of its neuroprotective effects.

It has been approved that selective serotonin reuptake inhibitors (SSRIs) may exhibit anti-proliferative or cytotoxic effects on several types of cancers. The aim of the present study was to evaluate the cytotoxic effects of a newly formulated niosome of Escitalopram oxalate on a colorectal cancer cell line.

The niosomes were prepared using a thin layer hydration method, resulting in particles with a size range between 150 – 450 nm and spherical morphology. Moreover, its permeability release showed 25% in 4 hours. The cytotoxicity evaluation was performed using a quantitative colorimetric MTT assay.

The cell viability of colon cancer cells after treatment with niosomes and pure escitalopram reduced to 28.3 ± 0.83 % and 24.07 ± 0.56%, respectively. However, the cytotoxicity assay of escitalopram-loaded niosomes suggested that the anti-proliferative effect of the niosomal formulation of escitalopram was dose and incubation time-dependent.

These results confirm the potential of the anti-proliferative activity of escitalopram-loaded niosomes. Further application to an in vivo model is needed to study various pharmacokinetic and pharmacodynamics parameters to establish its complete therapeutic potential.

Two of the most important ion channels in the smooth muscle membrane are L-type and T-type calcium channels. L-type calcium channels are responsible for smooth muscle contraction, while T-type calcium channels are involved in cell membrane depolarization.

In this study, a model consisting of 1200 cells was used to simulate the smooth muscle of the gastric wall. The paper explores the effects of blocking 10%, 50%, 90%, and 100% of L-type and T-type calcium channels on the spatiotemporal wavefront propagation in human gastric wall smooth muscle cells, simulated separately.

The results showed that complete blockage had the most significant effect on the slow-wave. Blockage of the L-type calcium channel led to a reduction of -3.4% and -0.8% in the membrane potential during the spike and plateau phases, respectively. The T-type calcium channel reduced the spike and resting membrane potential by -1.8% and -0.9%, respectively. In addition, the L-type calcium channel exhibited a greater impact on reducing muscle contraction compared to the T-type calcium channel. This suggests that higher blockage of calcium channels led to decreased membrane potential during slow-wave phases and reduced muscle contraction, compared to the physiological state.

Blocking ion channels in electrophysiological models can potentially help control gastrointestinal tract motility disorders and smooth muscle contraction.