Physiology and Pharmacology
Volume:27 Issue: 1, Mar 2023

Carbon monoxide (CO) intoxication is one of the most important poisonings related to high morbidity and mortality rate. The main treatment of CO poisoning is oxygen therapy using normobaric (NBO) or hyperbaric oxygen (HBO). However, more pharmaceutical agents are needed to improve CO poisoning treatment, especially in severe cases. Recently, erythropoietin (EPO) has been examined in several studies, showing a significant reduction in cardiac and neural sequels of CO poisoning.In this article, the effect of EPO on cardio and neurotoxicity of CO poisoning were reviewed. For this purpose, EPO effect on CO poisoning was searched in papers published until 2020 using Pubmed, Scopus, and google scholar. Only English papers on three main databases have been reviewed. The review of several animal and clinical studies have been shown that EPO administration after CO poisoning could improve neurological function and reduce CO-neurotoxicity significantly. Although there is good evidence of EPO effects on CO-induced-neurological sequelae, further clinical studies are needed to establish its benefit on CO intoxication.

Melasma is a common skin problem in pregnant women that appears to be related to physiological changes. Mesenchymal stem cells (MSCs) have been used to treat skin disorders because of their direct cell-to-cell contact or release of several biomolecules. The umbilical cord, which is available at birth, is a rich source of MSCs. This study was undertaken to evaluate the effect of the umbilical cord as a natural face mask for treating women’s melasma after parturition.

This randomized clinical trial was carried out on parturients suffering from melasma. Fifty pregnant women were randomly categorized into two groups of control and treated with the umbilical cord. A section of the umbilical cord (10-20 cm) was cut immediately after parturition and used as a face mask on the face of each mother in the hyperpigmentation areas for one hour. Melasma Area Severity Index (MASI) was used to measure hyperpigmentation and calculated for each participant before and four weeks after intervention.

A significant decrease in MASI was observed in the women treated with the umbilical cord (p<0.05).

Our findings suggested that a fresh umbilical cord, as a natural face mask containing MSCs, can improve the melasma in the parturients.

Respiratory exchange ratio (RER) is the ratio between produced CO2 and used O2 for body metabolism. It indicates the type of fuel that is metabolized in the body. This study aimed to measure and compare the RER in non-obese and obese sedentary young adults in rest, moderate-intensity, and vigorous-intensity exercise.

This cross-sectional study was conducted with 23 non-obese and 24 obese sedentary young adults. Resting RER was measured with 12-h fasting after 15-min rest with an automated gas analyzer. Then, RER was measured during steady moderate-intensity and vigorous-intensity exercise on a cycle ergometer. RER was compared between males and females, non-obese and obese in resting, moderate-intensity, and vigorous-intensity exercise by t-test.

The Mean age of the non-obese and obese groups was 19.35±1.11 and 19.79±0.78 years, respectively. Males showed higher RER (in resting and moderate-intensity exercise) than females. In comparison to non-obese group, the obese group showed higher RER in resting (0.802±0.018 versus 0.821±0.022, P=0.001), moderate-intensity exercise (0.812±0.013 versus 0.83±0.02, P<0.001), and vigorous-intensity exercise (0.853±0.43 versus 0.914±0.032, P<0.001). Concerning resting value, RER significantly increased during moderate- and vigorous-intensity exercise in both the non-obese and obese groups.

Obese young adults use relatively more carbohydrates as fuel than non-obese in both resting conditions and during exercise. When the intensity of exercise increased, both obese and non-obese showed higher RER which indicates that sedentary young adults use relatively more carbohydrates as fuel in the higher grade of exercise.

“Think–Pair–Share” (TPS) is an active cooperative teaching-learning method that encourages as well as allows for individual thinking, collaboration, and presentation. It offers the benefits of small group learning and the development of higher-order thinking skills. It provides immediate feedback to students on their understanding and teachers on the extent of pupil understanding. Thus it helps in modifying both teaching and learning. Hence the current study aimed at comparing the efficacy of TPS with tutorials and assessing the perception of students towards TPS.

42 students who met the eligibility criteria and consented to participate in the study were included after obtaining Institutional ethics committee clearance and written informed consent. There were 2 test groups. TPS was employed to teach Group 1 while Group 2 was taught by Tutorials simultaneously for 6 sessions. A pre-test and post-test were conducted for each session. A final Multiple choice question test was conducted at the end of the study. The perception of the participants towards TPS was also obtained.

Our study did not show a significant difference between the post-test, change in mean post-test over pre-test scores, and final test scores. The participants had a good perception regarding TPS and agreed that it was engaging and improved communication with the teacher. They felt that it also should be used in the future.

Although TPS failed to exhibit an improved efficacy, it can be used in the future because it promotes active learner participation, individual thinking, and communication skills as well as provides immediate feedback.

There is some evidence of significant differences in the recovery after spinal cord injury (SCI) between males and females. In this study, we investigated the sensory function and involvement of astrocytes in the sex differences of central pain syndrome in the unilateral spinothalamic tract (STT) injury model in rats.

Rats were divided into two groups: SCI and Sham groups received a unilateral electrolytic lesion on STT at T8-T9 and a control sham surgery respectively. After recovery from surgery, the sensory function was monitored for 28 days using tail flick and von Frey filament tests. The glial fibrillary acidic protein (GFAP) level was also measured by Western blot at the same time points.

Mechanical hypersensitivity was increased from days 3 to 28 post-injury in male rats (P<0.001), but no significant change was observed in females. In the tail flick model, male rats had significantly elevated thermal withdrawal latency on day3 after STT lesion, while females showed a reduction in latency (P<0.001). Sex differences in GFAP level were observed during 4 weeks of study after injury. Results in the first week showed that GFAP level decreased in females, but the marked elevation was observed from days 7 to 28 in males (P<0.05).

This study revealed the sex differences in sensory dysfunction and the related astrocyte reactivity after SCI. It suggests a need for more studies using both sexes to fully explore the influence of sex on the recovery of sensory impairments post-SCI.

Despite all the research, no definitive treatment for stroke has been found yet. Cinnamon is a plant that has been shown to have health benefits effects. In this study, the effect of pretreatment of cinnamon on ischemia tolerance and the expression of Zonula occludens 1(ZO-1) gene in the brains of rats receiving a high-fat diet was investigated.

In this study, 72 rats were divided into six groups: control, sham, model (stroke), vehicle, lovastatin, and cinnamon. All groups except the control group received a high-fat diet for 8 weeks. Then the last three groups received Carboxymethyl cellulose, lovastatin, and cinnamon 130 mg accordingly for 6 weeks. Stroke was induced by middle cerebral artery occlusion (MCAO). Twelve hours later, the animals were examined for the extent of serum lipids, brain edema, anti-oxidant capacity and gene expression of ZO-1.

Cinnamon was effective in reducing serum cholesterol and triglyceride. Cinnamon treatment significantly diminished brain edema. It also restored anti-oxidant capacity. ZO-1 gene expression was increased in the ischemic brains after cinnamon treatment (P< 0.05).

Pretreatment with Cin130 had beneficial effects on the serum lipid profile, edema volume in ischemic brain and anti-oxidant capacity. It increased ZO-1 gene expression and so maintained cellular integrity and prevented the subsequent edema.

Chronic stress is related to cognitive impairment. Azadirachta indica A. Juss. (A. indica) leaf extract possesses antioxidant and cognitive enhancement effects. Therefore, this study was set up to evaluate the cognitive-enhancing effects of A. indica flower extract in stressed rats.

Male Wistar rats were randomly divided into control and stress groups. Restraint stress was induced to stress groups 3 h daily. The stressed rats were given vehicles, donepezil (a positive control meditation used to improve cognition), and A. indica at 250, 500, and 1000 mg/kg BW for 30 days. The novel object recognition test (NORT) was used to assess cognitive function, and the open field test (OFT) was utilized to assess spontaneous locomotor activity. Their brains and blood were taken to measure levels of brain-derived neurotrophic factor (BDNF), blood cortisol levels, and the density of survival neurons.

The discrimination index ratio of the stressed rats treated with either donepezil or A. indica flower extract at all doses was significantly improved as measured by NORT. Moreover, there was no significant difference between the control and stress groups in the locomotor behaviors of rearing and number of crossing. The stressed rats treated with donepezil and A. indica flower extract had significantly higher BDNF levels and also survival neuron density in the brain. However, their blood cortisol levels were lower than the stressed rats given the vehicle.

A. indica flower extract helps improve cognitive function in stressed rats by boosting BDNF and protecting against neuronal loss in the brain.

Malathion (MAL), a kind of organophosphate pesticide (OPs), is one of the oldest phosphoric pesticides used for both domestic and commercial agricultural purposes. However, it possesses adverse effects and organ-specific toxicity for the heart, kidney, and other vertebrate organs. The exact effects of the short-term toxicity of MAL on lipid peroxidation, antioxidant activity, and pro-inflammatory cytokines have not been sufficiently elucidated yet.

We evaluated lipid peroxidation (MDA level), antioxidant activity [superoxide dismutase (SOD) and catalase (CAT)], tumor necrosis factor alpha (TNF-α), and Interleukin-1 beta (IL-1β) in different tissues of MAL-treated Wistar rats, at doses of 50, 100, and 200 mg/kg.

After 14 days of exposure, CAT and SOD activities and MDA level increased in most tissues. Based on the histopathological results, the liver, kidney, and heart were the most affected, while the testes and lungs showed no damage. Also, increased TNF-α was measured as an inflammatory cytokine compared to untreated rats. IL-1β levels showed a dual response to the toxic effects of MAL, such as an increase in testis, kidney, and lung tissues and reduced in liver, heart, and blood tissues.

The present findings reinforce the concept that MAL can cause tissue-specific damage while enhancing the activity of antioxidant enzymes and reducing cytokine levels.

Given some limitations in the efficacy of N-acetyl cysteine (NAC) or remote ischemic preconditioning (RIPC) to prevent contrast-induced nephropathy (CIN), the present study investigated the beneficial effects of NAC alone or in combination with RIPC on CIN prevention.

Rats were randomly assigned into five groups of eight animals each. Group 1 was sham-operated controls. In group 2, an experimental model of diatrizoate-induced CIN was induced. In groups 3 and 4, NAC (150 mg/kg orally, 24 h before the CIN induction) or RIPC (3 cycles of 4 min/4 min of ischemia and reperfusion in the forelimbs 24 h before the CIN induction) was applied, and both strategies were applied in group 5. 48 hours after the intervention, serum was collected to assess creatinine (Cr) and blood urea nitrogen (BUN) levels. Kidney tissue samples were also kept to evaluate the histology and measure malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity.

Considerable increases in serum Cr (0.82±0.04 vs 0.53±0.03 mg/dl) and BUN (49.87±2.85 vs 22.93±1.11 mg/dl) levels in the CIN group showed renal functional damages compared to the sham group. The morphological changes (2 vs 0 score), increased renal MDA levels (8.11±1.27 vs 3.12±0.52 μmol/100 mg tissue), and decreased renal SOD activity (2.29±0.65 vs 27.32±0.98 U/g tissue) in the CIN group represent a remarkable renal injury and oxidative stress compared to the sham group. The individual use of NAC (serum Cr levels: 0.59±0.01 mg/dl; serum BUN levels: 27.24±1.01 mg/dl; morphological changes: 1 score; renal MDA levels: 4.35±0.58 μmol/100 mg tissue; renal SOD activity: 17.24±1.48 U/g tissue) and RIPC (serum Cr levels: 0.60±0.03 mg/dl; serum BUN levels: 28.78±1.66 mg/dl; morphological changes: 1 score; renal MDA levels: 5.34±0.53 μmol/100 mg tissue; renal SOD activity: 13.11±1.96 U/g tissue) improved all indices above. However, the combination of NAC and RIPC (serum Cr levels: 0.57±0.01 mg/dl; serum BUN levels: 25.32±1.14 mg/dl; morphological changes: 1 score; renal MDA levels: 3.56±0.52 μmol/100 mg tissue; renal SOD activity: 30.54±2.92 U/g tissue) was more effective than other strategies used alone.

The combined use of NAC and RIPC may be more useful in preventing CIN than the individual use of possible additive effects through reducing oxidative stress.

Neural stem cells (NSCs) are multipotent stem cells residing in the central nervous system that is capable of self-renewal to support ongoing requirements for neurogenesis in the adult brain. Since NSCs are considered potential candidate cells for neuro-regenerative medicine, applying safe induction methods for them is very important. Synthetic modified-mRNA (mmRNA) as an alternative to traditional DNA- or protein-based methods, is regarded as a powerful tool for inducing short-term gene expression in cells with no genetic manipulation.

Here, we aimed to develop an optimized condition for mmRNA transfection in primary NSCs. In vitro-transcribed EGFP mmRNA (mmRNAEGFP) was delivered to human embryonic kidney cells (HEK293T) and mouse NSCs by using two commercial agents, Lipofectamine-2000 (LF2000) and TransIT. Also, a plasmid DNA was used to transfect cells considered EGFP-expressing positive control. In addition, the poly(A) tail (poly adenosine tail) elongation and chloroquine (CQ) treatment were performed to improve transfection efficiency. Finally, flow cytometry, fluorescence microscopy, and MTT assays were performed to assess the cells.

In comparison with HEK293T, NSCs were very sensitive to transfection, the efficacy of transfection using DNA/LF2000 was higher in HEK293T cells, but mmRNAEGFP/ TransIT showed better transfection efficacy in NSCs. Poly(A) tail elongation; also, treating the cells with CQ before transfection significantly improved its efficacy.

The mmRNA poly(A) tail elongation and the use of specific transfection agents in combination with TLR inhibitors can lead to a more effective transfection in NSCs.

Acute accidental and deliberate poisoning by medications and pharmaceuticals is the third cause of death in suicides after hanging and self-immolation. To determine the common pattern of intentional drug poisoning in Tehran, this descriptive and retrospective study has reviewed and analyzed the data related to the records of patients admitted due to intentional drug poisoning, 2018-2019 at Loghman-Hakim-Hospital-Poison-Center (LHHPC).

This is an epidemiological, cross-sectional investigation based on the medical profile of 9245 patients who were admitted to LHHPC for intentional drug poisoning from May 2018 to May 2019. The verified variables included: age, gender, type of drug used, previous history of mental health problems, presence or absence of a previous history of suicide, the outcome of hospitalization and time of emergency visit. All inquiry data were coded and statistically analyzed using SPSS Version 26 software.

The average age of the admitted cases was 29.3±12.4, with a minimum age of 12 years. The greatest proportion of poisoning occurred between the ages of 21-30 years. About 17.10% of patients had a previous history of self-harm and 57.77% had mental disorders. The most common pharmaceuticals for deliberate poisoning were anti-epileptics-sedative-hypnotics, antipyretics-non-opioid-analgesics, narcotics- hallucinogens and antidepressant-antipsychotic. Mortality was significantly higher in men and also following methadone and benzodiazepines.

The high prevalence of intentional poisoning and its resulting mortality among young adults requires considerable attention and further studies to understand the underlying causes. Besides, strict rules need to be enforced regarding the sale of central nervous system drugs and opioids.