Objective: Traditional denoising algorithms perform less due Limited Directional Selectivity problem and do not adequately capture directional information in pixels. Traditional algorithms' edge representation and texture details are insufficient for the earlier detection of DH. Limited Directional Selectivity leads to inaccurate diagnosis and classification of Disc Herniation (DH) stages. The DH stages are (i) Degeneration (ii) Prolapse (iii) Extrusion and (iv) Sequestration. Moreover, detection of DH size below 2mm using MR image is the major problem.

Methods: To solve the above problem, spinal cord MR images fed to the proposed Parrot optimization tuned Denoising Convolutional Neural Network (Po- DnCNN) algorithm for perspective enhancement of nucleus pulposus region in the spinal cord, vertebrae. The perspective enhancement of Spinal cord image led to the accurate classification of stages and earlier detection of DH by using the proposed Hippopotamus optimization- Fast Hybrid Vision Transformer (Ho–FastViT) algorithm. For this study, spinal cord MR images are obtained from the Grand Challenge website – SPIDER dataset.

Results: The proposed Po-DnCNN method and Ho-FastViT results are analysed quantitatively and qualitatively based on the edge, contrast, classification of the stage, and enhancement of the projected nucleus pulposus region in the spinal cord and vertebrae. The predicted DH results using the proposed method are compared with the manual Pfirrman Grade value of the spinal card method.

Conclusion: Proposed method is better than traditional methods for earlier detection of DH. Po-DnCNN and Ho-FastViat methods give high accuracy of about 98% and 97% compared to traditional methods.

Objectives: The purpose of this article is to provide a narrative review on the management of DKA.

Methods: A PubMed search was performed with clinical queries using the key term “diabetic ketoacidosis”. The search strategy included randomized controlled trials, clinical trials, meta-analyses, observational studies, guidelines, and reviews. The search was restricted to English literature and the age range of 18 years and younger. Moreover, we reviewed and compared major guidelines.

Results: Selected international guidelines for DKA, namely International Society for Pediatric and Adolescent Diabetes (ISPAD), National Institute for Health and Care Excellence (NICE), British Society for Paediatric Endocrinology and Diabetes (BSPED), and South Thames Retrieval Service (STRS) were reviewed. There are considerable differences in the management approaches for DKA between different countries. One of the main areas of differences between guidelines is the administration of fluid, with most guidelines adopting a restrictive approach. This is based on the concern over cerebral oedema, a lethal sequela allegedly to be caused by excessive fluid administration. However, recent new clinical studies suggest that there is no causal relationship between intravenous fluid therapy and DKA-related cerebral injury. The British Society of Paediatric Endocrinology updated its guideline in 2020 to adopt a more permissive approach to fluid administration, which has sparked controversy among some paediatricians.

Conclusion: The management of DKA involves early recognition, accurate diagnosis, meticulous fluid and insulin treatment with close monitoring of blood glucose, ketones, electrolytes, renal function, and neurological status. There is still limited clinical evidence to support either a restrictive or permissive approach in the fluid management of paediatric DKA patients. Clinicians should exercise caution when applying different guidelines in their clinical practice, considering the specific circumstances of individual paediatric patients.

Objective: The use of Memantine, a non-competitive antagonist with low to moderate affinity for the NMDA (N-methyl-D-aspartate) receptor, has been approved for the treatment of mild to moderately severe Alzheimer's disease (AD). The efficacy of cholinesterase inhibitors (ChEIs) in the treatment of dementia varies depending on the drug type and ease of administration. Numerous techniques have been employed to evaluate the quality of life (QOL) of individuals suffering from dementia. QOL data is a well-established measure of an intervention's effectiveness. Up to now, cost-effectiveness studies have concentrated on both pharmaceutical and non-pharmacological therapy. Each unit of QoL-AD improvement costs USD27.82578 at mean values.

Methods: Searches were conducted to observe studies of the pharmacoeconomic impact of dementia medications with the help of previous articles published in journals and collected from Google Scholar with name search dementia or Alzheimer's cross-referenced with pharmacoeconomic or costs and effectiveness.

Objective: To create a systematic correlation between the disease and locate the exact mechanism and receptors responsible for it. So, this article covers a proper way to resolve the conditions and their manifestation through literacy and diagrammatic.

Conclusion: Hence, this will be an insight for many scholars to understand the exact mechanism involved in the process.

Method: According to the PRISMA guideline, a systematic search was accomplished to identify all relevant scientific papers on “the role of resveratrol against cisplatin-induced ototoxicity” in different electronic databases up to May 2021. Fifty-five articles were screened based on a predefined set of inclusion and exclusion criteria. Eight eligible studies were finally included in the current systematic review. The in-vitro findings revealed that cisplatin administration significantly decreased the HEI-OC1 cell viability compared to the untreated cells; however, resveratrol co-treatment (in a dose-dependent manner) could protect HEI-OC1 cells against cisplatin-induced decrease in cell viability.

Results: Furthermore, the in-vivo finding showed a decreased value of DPOAE, and increased values of ABR threshold, ABR-I, ABR-IV, and ABR I-IV interval in cisplatin-treated animals; in contrast, resveratrol co-administration demonstrated an opposite pattern on these parameters.

Conclusion: Thus, it can be mentioned that resveratrol co-treatment alleviates cisplatin-induced ototoxicity. Mechanically, resveratrol exerts its otoprotective effects through various mechanisms such as anti-oxidant, anti-apoptosis, and anti-inflammatory.

Background: This study aimed to evaluate the sub-chronic toxicity of Z. roseum, commonly known as rosy ginger, using a mouse model. Z. roseum has been traditionally used for its medicinal properties; however, there is limited information regarding its potential toxic effects.

Objective: The objective of this study is to assess the safety profile of ZRR extract at various doses and conduct a detailed analysis of hematological, biochemical, and histological parameters regarding sub-chronic toxicity.

Methods: Mice were orally administered ZRR methanolic extract at doses of 300, 600, and 1200 mg/kg for 14 days as per the guidelines of ‘The Brazilian Agency of National Health Surveillance.’ Subchronic toxicity was conducted by monitoring multiple indicators, including changes in body weight, food and water consumption, blood profile (HB, RBC, WBC, and PLT), and biochemical markers (ALT, AST, ALP, TP, ALB, TC, TG, HDL, LDL, Creatinine, and Urea) and histopathological examination of the liver.

Results: Throughout the study, the mice showed normal behavior and appeared healthy. The administration of Z. roseum at all tested doses did not significantly affect body weight, food, and water intake, blood, biochemical markers, or liver. Z. roseum at these doses was safe, with no fatalities or harm.

Conclusion: Lastly, the sub-chronic administration of Z. roseum at doses of 300, 600, and 1200 mg/kg in a mice model did not elicit any toxic effects, indicating its potential safety as a therapeutic agent.

Objective: This study aims to get more insights into the role of inflammatory cytokines and chemokines during the development of osteoarthritis and to evaluate a possible blocking strategy using anti-inflammatory molecules, we resort to an in vitro experimental model using an established human chondrosarcoma cell line that underwent to a well known pro-inflammatory stimulus as bacterial lipopolysaccharide.

Methods: We tested the production of inflammatory-related cytokines and chemokines, and the efficacy of low-dose (LD) administration of anti-inflammatory compounds, namely IL-10 and anti-IL-1, to block inflammatory cellular pathways.

Results: Following an inflammatory insult, chondrocytes upregulated the expression of several pro-inflammatory cyto-/chemokines and this induction could be counteracted by LD IL-10 and anti-IL-1. We reported that these effects could be ascribed to an interfering effect of LD drugs with the NF-κB signaling.

Conclusion: Our results provided a good indication that LD drugs can be effective in inhibiting the inflammatory response in chondrocytes opening the way to new therapies for the treatment of diseases such as osteoarthritis.

Objective: The capability of the unconventional Accelerated Stability Assessment Program (ASAP) to decode chemical stability and expedite shelf-life prediction is discussed in the manuscript.

Methods: As per the ASAP approach, shelf-life limiting attributes for two APIs’ and a formulation were identified based on the isoconversion ratio. Isoconversion times at varying accelerated conditions were obtained and the degradation kinetics were modeled using the humidity-modified Arrhenius equation. R2 and Q2 values were derived to assure model predictability. Temperature and humidity sensitivity of the attributes were determined from the activation energy; Ea, and humidity sensitivity factor, B, respectively. Degradation plots demonstrated the dynamics of degradation with time. The predicted values were verified by the available real-time data.

Results: The degradation rate was modeled for impurities that exhibited conversion substantiated by an isoconversion ratio between 0.25-2.0. The Ea and B data provided valuable details regarding the sensitivity of the products. Predicted shelf-life of less than a year for the finished product instigated redevelopment. In the case of the APIs’, the existing storage conditions were found unsuitable for shelf-life stability, and alternate conducive conditions were identified.

Conclusion: The study provided cognizance regarding the distinct degradation pattern of an API and its formulation and the contradictory storage requirement for APIs’ of two different molecules. While the traditional approach claims 3-6 months to predict shelf-life, the ASAP approach provides the same with enhanced accuracy in just 3-4 weeks.

Objective: In this work, we aimed to summarize the interesting results from preclinical and clinical studies that assessed the effects of natural alkaloids (berberine, nigelladine A, piperine, trigonelline, capsaicin, nuciferine, evodiamine, mahanine, and magnoflorine) on impaired insulin sensitivity and worsened insulin resistance, which play a pivotal role in the pathogenesis of type 2 diabetes.

Methods: In the current review, PubMed, ScienceDirect, Springer, and Google Scholar databases were used. The inclusion criteria were based on the following keywords and phrases: insulin sensitivity, insulin resistance, alkaloids and insulin resistance, alkaloids and type 2 diabetes, mechanisms of action, and alkaloids.

Results: The outcomes reported in this review demonstrated that the selected alkaloids increased insulin sensitivity and reduced insulin resistance in vitro and in vivo evidence, as well as in clinical trials, through improving insulin-signaling transduction mainly in hepatocytes, myocytes, and adipocytes, both at cellular and molecular levels. Insulin signaling components (InsR, IRS-1, PI3K, Akt, etc.), protein kinases and phosphatases, receptors, ion channels, cytokines, adipokines, and microRNAs, are influenced by alkaloids at transcriptional and translational levels, also in terms of function (activity and/or phosphorylation). Multiple perturbations associated with insulin resistance, such as ectopic lipid accumulation, inflammation, ER stress, oxidative stress, mitochondrial dysfunction, gut microbiota dysbiosis, and β-cell failure, are reversed after treatment with alkaloids. Furthermore, various indices and tests are employed to assess insulin resistance, including the Matsuda index, insulin sensitivity index (ISI), oral glucose tolerance test (OGTT), and insulin tolerance test (ITT), which are all enhanced by alkaloids. These improvements extend to fasting blood glucose, fasting insulin, and HbA1c levels as well. Additionally, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and the Homeostasis Model Assessment of β-cell function (HOMA-β) are recognized as robust markers of insulin sensitivity and β-cell function, and it is noteworthy that alkaloids also lead to improvements in these two markers.

Conclusion: Based on the findings of the current review, alkaloids may serve as both preventive and curative agents for metabolic disorders, specifically type 2 diabetes. Nonetheless, there is an urgent need for additional clinical trials to explore the potential benefits of alkaloids in both healthy individuals and those with type 2 diabetes. Additionally, it is crucial to assess any possible side effects and interactions with antidiabetic drugs.

Methods: Diabetic ketoacidosis is more common in type 1 diabetic patients, although it can also be fall in type 2 diabetic patients. DKA occurs when the body lacks enough insulin to allow blood sugar to enter the cells and is used for energy. Instead, the liver breaks down fat for fuel-producing chemicals known as ketones.

Results: When too many ketones are created too quickly, they can reach dangerously high levels in the body. Mucormycosis is a rare but serious infectious disease that requires medication or surgical removal.

Conclusion: The confluence of diabetes and COVID-19 makes managing mucormycosis a serious and dead issue. Although the effectiveness of prophylactic antifungal therapy has yet to be demonstrated, hyperglycemia control appears to be the most important step in managing mucormycosis in DKA patients.

Methods: This study was carried out on 165 cases of COVID-19 and 138 controls. ACE2 and MCP1 levels were measured in COVID-19 cases and control by ELISA and micro-RNA-146 expression by PCR.

Results: We found an increased blood level of ACE2 and MCP1 in COVID- 19 patients than in healthy persons and a significant down-regulation of micro-RNA 146 gene expression in cases than in controls. There was a significant correlation between increased blood level of ACE2, regulation of micro-RNA 146 gene expression and severity of lung affection, a significant correlation was found between increased blood level of MCP1 and thrombosis in COVID-19 patients. Neurological complications were significantly correlated with more viral load, more ACE2 blood level, and down regulation of micro RNA146 expression.

Conclusion: High viral load, increased blood level of ACE2, and down-regulation of micro-RNA 146 expression are associated with more severe lung injury and the presence of neurologic complications like convulsions and coma in COVID-19 Egyptian patients.

Case Presentation: Here, a 55-year-old lady was referred with a history of diffuse headache and intermittent fever for two months, projectile vomiting, and altered mental status for five days. Nonpruritic maculopapular rashes and diffuse desquamation of the skin were noted. She had no significant previous medical history. Based on clinical findings and investigations, she was diagnosed with ICL having disseminated cryptococcosis. Unfortunately, the patient did not undergo specific treatment as she was recognized late, and unfortunately, she died.

Conclusion: It is of paramount importance to recognize the clinical entity as early as possible to start appropriate treatment, which may positively impact the outcome. Therefore, the clinician must be aware of disseminated cryptococcosis associated with non-HIV states.

Case Presentation: We report a case series of patients with advanced kidney disease and baclofen-induced encephalopathy that settled with discontinuation of the drug and hemodialysis sessions.

Conclusion: We report this cluster of patients with baclofen toxicity to highlight the common occurrence of neurotoxicity after its use in patients with end-stage renal disease and its resolution after cessation of the drug and hemodialysis sessions.]]> https://www.benthamscience.comarticle/126271 https://www.benthamscience.comarticle/121429Background: The COVID-19 pandemic has encouraged doctors to look for novel ways of treating patients with respiratory failure due to the limited availability of ventilators and highflow nasal cannula. The study aims to assess the efficacy of using the Bains circuit as an alternative to HFNC and NIV as life-saving tools in patients with respiratory failure during the second wave of the COVID-19 pandemic in India.

Methods: This is a prospective interventional study carried out in the intensive care unit of Shri B.M Patil Medical College Hospital and Research Centre, Vijayapur, India, from May 2021 to June 2021. All patients (n=90) with respiratory failure not responding to therapy with an oxygen mask were included. Patients were placed on Bain circuits, one end connected to a non-invasive ventilation mask fitted to the face of the patients, and the other end connected to a central oxygen port. Patients’ vital parameters were assessed on an hourly basis. The blood gas analyses were done before and after using Bains.

Results: The study showed diabetes (33.4%), hypertension (22.2%), and diabetes with hypertension (11.1%) as comorbid factors among the ICU admitted patients. The results from the arterial blood gas analyses showed a statistically significant increase in Sp02 (%) and a decrease in respiratory rate (cycles/min) in the patients after being kept on Bains (p<0.05). Further, it showed that 72% of ICU patients with 70-79% Sp02 had a recovery by using Bains. The overall outcome of ICU admitted COVID-19 patients on Bains showed that 38.9% of patients improved and were shifted to 02/NRBM masks.

Conclusion: The study highlights a novel concept of using the Bains circuit as an effective alternative to HFNC and NIV for oxygenation in critically ill COVID-19 patients during scarcity of NIV and HFNC at the peak of the pandemic.]]> https://www.benthamscience.comarticle/121118 https://www.benthamscience.comarticle/117202Background: This study was conducted by considering the vital role of Vascular Endothelial Growth Factor (VEGF) in the development of Diabetic Retinopathy (DR) on the one hand and the frequent association between Subclinical Hypothyroidism (SCH) and DR on the other hand.

Objective: The present study was proposed to explore the possible role of VEGF in the relation between SCH and DR; thus, we investigated the relationship between SCH and VEGF levels in patients with DR.

Methods: Two hundred patients with DR were recruited in this study [100 patients with Proliferative Diabetic Retinopathy (PDR) and 100 patients with Non-Proliferative Diabetic Retinopathy (NPDR)]. Patients with DR were divided into 2 groups according to thyroid function, patients with SCH or those with euthyroidism. Patients were subjected to careful history taking and underwent clinical and ophthalmological examination. Fasting blood glucose, glycosylated hemoglobin, fasting insulin, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), TSH, FT4, FT3, VEGF, and thyroid volume were assessed.

Results: Among all the studied patients, 21.5% (43/200) had SCH. DR patients with SCH had older age, longer diabetes duration, and higher HbA1c, HOMA-IR, and VEGF than those with euthyroidism. The frequency of PDR in patients with SCH was 72.1% (31/43) and 43.9% (69/157) in those with euthyroidism, whereas the frequency of NPDR in patients with SCH was 27.9 (12/43) and 56.1% (88/157) in those with euthyroidism (P 0.003). In multivariate analysis, PDR, HOMA- IR, and VEGF levels were the significant predictor variables of SCH.

Conclusion: Increased VEGF levels may be implicated in the relationship between SCH and DR.

Objective: This article aimed to provide a comprehensive overview of the anticancer effects of naphthoquinone compounds through a detailed review of literature and Chinese patents, and discuss their potential to be developed as anticancer drugs for clinical application.

Methods: Research papers were collected through the databases of PubMed, Cnki and SciDirect using keyword searches “naphthoquinone compounds” and “anticancer”. The keywords of “shikonin” and “shikonin derivatives” were also used in PubMed, Cnki and SciDirect databases to collect research articles. The Chinese patents were collected using the Cnki patent database.

Results: Naphthoquinone compounds have been found to possess anti-cancer activity, and their modes of action are associated with inducing apoptosis, inhibiting cancer cell proliferation, promoting autophagy in cancer cells, anti-cancer angiogenesis and inhibition of cell adhesion, invasion and metastasis, inhibiting glycolysis and inhibiting DNA topoisomerase activity.

Conclusion: Most of the naphthoquinone compounds show effective anti-cancer activity in vitro. The structure modification of naphthoquinone aims to develop anti-cancer drugs with high efficacy and low toxicity.

Objective: The current research paper was targeted to evaluate the potential effects of Ech on male fertility, and to highlight the possible involved mechanisms.

Methods: Eighteen adult male rats were randomly distributed into three groups: control (1 ml of 2% DMSO, p.o.), low dose Ech (0.1 mg/kg, p.o.), and high dose Ech (1 mg/kg p.o.).

Results: The high dose Ech caused a significant decline in the levels of glucose, ALT, AST, ALP, urea, Cr, uric acid, TG, TC and LDL-C and testicular tissue MDA, while it caused a significant rise in the levels of albumin, TP, HDL-C, FSH, LH, testosterone and testicular tissue GSH activity. Moreover, it showed a significant positive effect on the testis weight, caudal epididymis weight, sperm count, sperm motility, sperm morphology, fructose concentration, and α-glucosidase activity. However, no significant changes were observed in the histological examination of testicular tissue among all groups.

Conclusion: High dose Ech improved male rat-fertility either directly by activating the pituitarygonadal axis, and or indirectly via enhancing the renal and hepatic functions, the lipid profile and or the antioxidant pathways.

Methods: Chinese patients with T2DM were recruited and divided into two groups based on the Montreal Cognitive Assessment score. Demographic data were collected, LPL was measured and neuropsychological test results were examined.

Results: Seventy-nine patients with diabetes and MCI had significantly decreased plasma LPL levels (p = 0.007) when compared with health-cognition controls (n = 91). Correlation analysis revealed that LPL was positively correlated with clock drawing test (r = 0.158, p = 0.043) and logical memory test (r = 0.162, p = 0.037), while lipoprotein a (r = -0.214, p = 0.006) was inversely associated with LPL. Logistic regression analysis further demonstrated that LPL concentration was an independent factor for diabetic MCI (p = 0.036). No significant differences were observed in the distributions of rs328 variants between patients with MCI and the controls. Moreover, no remarkable association was found among plasma LPL levels, cognitive performances, and lipid levels between the genotypic subgroups. The trail making test A was increased in the GC group when compared with the CC genotype in the control group.

Conclusion: Decreased plasma level of LPL could probably predict early cognitive deficits, especially verbal disfluency.

Objective: To identify all the potential adverse reactions due to minocycline and analyze them in terms of the number of cases reported so far, salient features, severity and clinical outcome.

Methods: Comprehensive PubMed search of English and non-English literature for case reports of adverse reactions to minocycline was conducted.

Results: A total of 550 cases were identified from over 200 publications. The major reported adverse events caused by minocycline are drug reaction with eosinophilia and systemic symptoms syndrome, autoimmune syndromes like hepatitis, lupus and vasculitis, acute eosinophilic pneumonia, pseudotumor cerebri, hyperpigmentation, serum sickness-like reaction, Sweet’s syndrome and drug fever. Several other reactions involving multiple organ systems have also been reported. These show an overlap of clinical features and may be associated with multiple events causing considerable morbidity. Eight of these cases resulted in the death of the patients.

Conclusion: In view of the evident potential of minocycline to cause long-lasting and severe adverse effects, significant morbidity and even mortality, it should be prescribed with caution in the first-line treatment for moderate to severe acne.

Methods: Per-oral sub-acute toxicity study was performed in rats using three dose levels (200, 400 and 800 mg/kg b.w.) of the extract for 28 days. The control group received gum acacia suspended in water. Bodyweight was measured weekly. Biochemical parameters were analysed using the serum; the blood-cell count was performed using the whole blood. Pathological changes were also checked in highly perfused tissues. Further, in-vitro reducing power assay, nitric oxide scavenging assay, and DPPH free-radical scavenging assay were performed to evaluate the antioxidant activity of the extract.

Results: There were no significant alterations found in the blood-cell count and biochemical parameters analysed in the treatment group when compared with the normal control. Histopathology study of liver, kidney, pancreas, heart and brain revealed normal cellular architecture in the treatment groups alike the control group animals. Quercus serrata also showed a significant reduction of DPPH with an IC₅₀ value of 4.48±0.254 μg/mL, in-vitro reducing power activity with an IC₅₀ value of 121.65±0.320 μg/mL and nitric oxide scavenging activity with an IC50 value of 106.43±0.338 μg/mL.

Conclusion: The study showed that standardized methanolic extract of Quercus serrata leaves was safe after sub-acute oral administration in rats and possesses good antioxidant potential.]]> https://www.benthamscience.comarticle/112331Objective: Extensive retinal ischemia caused by proliferative diabetic retinopathy (PDR) may develop into neovascular glaucoma (NVG). We searched for the proteins which might participate in neovascularization through the analysis of aqueous humor (AH) proteomics in patients with NVG secondary to PDR to increasing the understanding of the possible mechanism of neovascularization.

Methods: We collected 12 samples (group A) of AH from patients with NVG secondary to PDR as the experimental group and 7 samples (group B) of AH from patients with primary acute angle-closure glaucoma (PAACG) & diabetes mellitus without diabetic retinopathy (NDR) as the control group. Differential quantitative proteome analysis of the aqueous humor samples was performed based on the data-independent acquisition (DIA) method. The differentially expressed proteins were functionally annotated by Ingenuity Pathway Analysis (IPA). The important differentially expressed proteins were validated in another group (group A: 5 samples and group B: 5 samples) by parallel reaction monitor (PRM) approach.

Results: A total of 636 AH proteins were identified, and 82 proteins were differentially expressed between the two groups. Functional annotation showed that the differentially expressed proteins were mainly associated with angiogenesis and cell migration. Signaling pathways analysis showed that the proteins up-regulated in group A were mainly related to Liver X receptor/Retinoid X receptor (LXR/RXR) activation and acute reaction.

Conclusion: This study presented a pilot work related to NVG secondary to PDR, which provided a better understanding of the mechanisms governing the pathophysiology of NVG.

Objective: This study explored pyroptosis of retinal neurons and the effects of melatonin in preventing retinal neurons from pyroptosis after acute HIOP injury.

Methods: An acute HIOP model of rats was established by increasing the IOP followed by reperfusion. Western Blot (WB) was adopted to detect molecules related to pyroptosis at the protein level, such as GSDMD, GASMDp32, Caspase-1, and caspase-1 p20, and the products of inflammatory reactions, such as IL -18 and IL-1β. At the same time, immunofluorescence (IF) was used to co-localize caspase-1 with retinal neurons to determine the position of caspase-1 expression. Morphologically, ethidium homodimer III staining, a method commonly used to evaluate cell death, was carried out to stain dead cells. Subsequently, Lactate Dehydrogenase (LDH) cytotoxicity assay kit was used to quantitatively analyze the LDH released after cell disruption.

Results: The results suggested that pyroptosis played a vital role in retinal neuronal death, especially in the Ganglion Cell Layer, by acute HIOP injury and peaked at 6h after HIOP injury. Furthermore, it was found that melatonin (MT) might prevent retinal neurons of pyroptosis via NF-κ B/NLRP3 axis after HIOP injury in rats.

Conclusion: Melatonin treatment might be considered a new strategy for protecting retinal neurons against pyroptosis following acute HIOP injury.

Objective: To determine whether the inflammatory cytokines in the tear film of patients with dry eye correlate with parameters such as Tear Break-Up Time (TBUT) and Tear Meniscus Height (TMH) and could be used together as predictive biomarkers of disease severity.

Methods: This study included 58 eyes (29 female subjects; age, 19–25 years) comprising 20 normal eyes (control), 20 eyes (level 1 dryness), and 18 eyes (level 2 dryness). Dryness level 1 or 2 is keratographic diagnosis according to the tear break-up time cut-off value obtained. After ophthalmic examinations, including determination of non-invasive TBUT average and first second and TMH using Keratograph 4 (to measure dryness level), tears of all participants were collected. Five cytokines, including interleukin 6, 10, 12, interferon-γ, and tumor necrosis factor-α, were measured using ELISA.

Results: Significant changes were observed in all measured cytokines and these changes correlated with eye dryness severity scores. Both groups (levels 1 & 2) showed remarkable changes related to ocular surface alterations in clinical examinations. Significantly, shorter TBUT and TMH were recorded in both groups and were positively correlated with the dryness severity.

Conclusion: Cytokines could be used as predictive markers for pre-clinical diagnosis of dry eye diseases and as prognostic markers to monitor treatment effectiveness.

Objective: The main objective of this review is to deeply discuss the role of biotransformation in the occurrence of antidepressant and anticonvulsant induced inter individual variabilities with the focus on genetic variations and drug interactions.

Methods: An extensive search of the literature has been conducted related to biotransformation of the antidepressant and anticonvulsant agents on relationships between genetic differences and drug interactions on available databases. Following keywords are used for relevant articles: “metabolic enzyme”, “pharmacokinetic”, “antidepressant”, “anticonvulsant”, “genetic variations”, “enzyme inhibition”, “enzyme induction” and also with a list of all included antidepressant and anticonvulsants.

Results: In the present review, we provided an overview of documented clinically significant pharmacokinetic drug interactions, physiological and environmental differences. We further discuss the significance of genetic variations in drug metabolizing enzymes to underline the need for using the information on both genotype and drug interactions towards implementing better clinical outcomes through personalized medicine in neurology and psychiatry.

Conclusion: The present review clearly illustrates that interindividual differences in the biotransformation (including genetic variability of the drug metabolizing enzymes, age, sex, diet) of the antidepressant and anticonvulsant drugs, which are commonly prescribed medications globally, has a crucial role in the occurrence of adverse effects and various drug responses. Therefore, the potential results of the drug-drug interactions and individual genetic characteristics should always be considered to make pharmacotherapy safer and more effective, as they have major clinical implications.

Case Presentation: We described the case of a pregnant woman complaining of nausea, vomiting and weight loss. Diagnosis of gestational PHPT (GPHPT) was made based on elevated serum calcium and parathyroid hormone levels (3.4 mmol/L and 41.6 pmol/L). Neck ultrasound documented a nodule suggestive of enlarged parathyroid, whereas the abdomen ultrasound revealed renal microlithiasis. Conservative treatment was started with oral hydration and a low-calcium diet. Clinical and biochemical monitoring was weekly and multidisciplinary. Despite our suggestion, the patient refused parathyroidectomy in the second trimester. Additional intravenous fluid rehydration from the 15th to the 25th week of gestation ameliorated the symptoms rapidly, and reduced calcium levels progressively from the 23rd week. At week 40, the woman gave birth to a healthy girl. At month 8 postpartum, calcemia and PTH were still elevated, and accompanied by osteoporosis and nephrocalcinosis. Surgery was accepted, and a parathyroid adenoma was removed.

Conclusion: In the absence of guidelines for GPHPT management, its treatment should be individualized. In our case, despite high calcium levels, conservative treatment with strict monitoring led to a positive outcome of pregnancy.

Objective: This review aimed to discuss the impact of probiotics/prebiotics and supplements on the prevention and treatment of respiratory infections, especially emerging pathogens.

Methods: The data were searched in PubMed, Scopus, Google Scholar, Google Patents, and The Lens-Patent using keywords of probiotics and viral respiratory infections in the title, abstract, and keywords.

Results: Probiotics consumption could decrease the susceptibility to viral respiratory infections, such as COVID-19 and simultaneously enhance vaccine efficiency in infectious disease prevention through the immune system enhancement. Probiotics improve the gut microbiota and the immune system via regulating the innate system response and production of anti-inflammatory cytokines. Moreover, treatment with probiotics contributes to intestinal homeostasis restitution under antibiotic pressure and decreasing the risk of secondary infections due to viral respiratory infections. Probiotics present varied performances in different conditions; thus, promoting their efficacy through combining with supplements (prebiotics, postbiotics, nutraceuticals, berberine, curcumin, lactoferrin, minerals, and vitamins) is important. Several supplements reported to enhance the probiotics’ efficacy and their mechanisms as well as probiotics- related patents are summarized in this review. Using nanotechnology and microencapsulation techniques can also improve probiotics’ efficiency.

Conclusion: Given the global challenge of COVID-19, probiotic/prebiotic and following nutritional guidelines should be regarded seriously. Additionally, their role as an adjuvant in vaccination for immune response augmentation needs attention.

Purpose: The present study is aimed to assess the safety and efficacy of intravitreal injection of Ranibizumab (IVR) versus intravitreal Dexamethasone implant (IVD) in patients with DME in a tertiary care centre upto 4 months.

Methods: This is a comparative, prospective, randomized study that was done on 140 patients with macular edema confirmed on optical coherence tomography (OCT). IVD group received Ozurdex® (Allergan, Inc, Ireland) while the IVR group received Lucentis® (Novartis, Basel, Switzerland); the groups were followed up at day-1 and weeks 4, 8, 12, 16. Patients were divided into Group A, in which patients were given 3 doses (monthly) of IVR 0.3 mg in 0.05 ml (n=70). Group B patients were given a single dose of IVD implant 0.7 mg (n=70).

Results: The mean number of injections given was 1 Ozurdex® per patient vs. 3 Lucentis® per patient. The maximum reduction in central macular thickness (CMT) with IVD was 167.8 μm and 138.8μm in the 2nd and 3rd months, respectively, with IVR. The mean best-corrected visual acuity (BCVA) in the 4th month was 0.34 logMAR and 0.33 logMAR, in IVD and IVR groups, respectively, with consistent improvement. Patients with 0-5 letters, 6-10 letters and 10-15 letters, and >15 letters visibility in IVD group were 9.5, 20.6, 4.8, 6.4%, and 20.4, 18.8, 20.3 20.3% in IVR groups, respectively. The maximum intraocular pressure (IOP) rise with IVD was found to be 16 mmHg in 2 patients (3.17%). IOP rise >10 mmHg was observed in 14/63 patients (22.22%); the majority of patients indicated a high rise at 2nd month with all returning to baseline by 4th month. No reports of infectious endophthalmitis or new cataracts were detected in either of the treated groups.

Conclusion: Both intravitreal Ranibizumab injection and Dexamethasone implants were found to be safe and effective in lowering CMT and improving BCVA at the 4-month follow up in patients with DME. Since there was no recurrence of CMT in the Dexamethasone implant group, we suggest that early administration before the 4th month may indicate superior efficacy over the ranibizumab injection. Further randomized trials in a large sample size with a longer period follow- up would be performed to justify the obtained results in the present study.

Methods: We searched Pub Med (132 articles) and Google scholar (9 articles) databases and gathered the clinical (4 articles), and preclinical (28 articles) studies, reports on cell culture models (30 articles), and other original and review articles (78 articles) related to inflammation, cancer, and cannabinoids.

Results: Cannabinoids are described in three different forms, comprising endo- phyto- and synthetic compounds that exert biological effects. The molecular and cellular pathways of endogenous cannabinoids in the maintenance of homeostasis are well documented. In addition to classical cannabinoid receptors type 1 and 2, Vanilloid receptors and G protein-coupled receptor 55 were identified as common receptors. Subsequently, the effectiveness of phyto- and synthetic cannabinoids mediated by cannabinoid receptors has been demonstrated in the treatment of inflammatory diseases, including neurodegenerative diseases as well as gastrointestinal and respiratory inflammations. Another accepted property of cannabinoids is their anti-cancer effects. Cannabinoids were found to be effective in the treatment of lung, colorectal, prostate, breast, pancreas, and hepatic cancers. The anti-cancer effects of cannabinoids were characterized by their anti-proliferative property, inhibition of cancer cell migration, suppression of vascularization, and induction of apoptosis.

Conclusion: The current review provides an overview of the role of the endocannabinoid system in the mediation of physiological functions and the type and expression of cannabinoids receptors under physiological and pathological conditions. In addition, the molecular pathways involved in the effects of cannabinoids and the effectiveness of cannabinoids in the treatment of inflammations and cancers are highlighted.

Methods: The goal of the review was to comprehensively study the utilization of nanotechnology and the role that carbon nanotubes can play as a drug delivery system for the amelioration of Alzheimer’s disease.

Results: Nanotechnology is one of the most researched domains of modern science. It contributes significantly to therapeutics by facilitating drug therapy to reach the target sites, which are otherwise difficult to reach with conventional drug delivery systems. Carbon nanotubes are the allotropes of carbon in which several carbon atoms bind with each other to form a cylindrical or a tube-like structure. The carbon nanotubes possess several unique qualities, which confer them with a high potential of being utilized as an efficient drug delivery system. They offer high drug loading and can readily cross the toughest biological barriers like the BBB. Carbon nanotubes also facilitate the passage of drugs to the brain via the olfactory route, which further helps in restoring normal autophagy, thus preventing the elimination of autophagic chemicals. They can carry a vast range of cargos, including drugs, antigens, genetic materials, and biological macromolecules.

Conclusion: Carbon nanotubes are a highly promising drug delivery system for anti-Alzheimer’s drugs. They have the potential of overcoming the various biological barriers like the BBB. However, more extensive research is required so as to set up a firm base for the development of advanced commercial products based on carbon nanotubes for the treatment of Alzheimer’s disease.

Introduction: The increase in the number of hematological malignancy-related cases in our modern society urges suitable treatment of such disease. In this current era, there is still a major deficiency in the number of suitable chemotherapeutic agents for the treatment of hematological malignancies.

Methods: The researchers were successful in identifying various cellular, extracellular proteins, and cytokines, as well as their involvement in different hematological malignancies via epigenetic modulation and regulation of other proteins and signaling pathways. Here, we have discussed the structural aspects, connection, and pathophysiological contributions of a group of different cellular and extracellular proteins that are regulated and/or have a significant influence on the progression of different hematological malignancies along with their potent inhibitors.

Result and Conclusion: The correlation of physiological proteins with cancerous hematological conditions has been discussed here. It can be crucial for the development of potent inhibitors as chemotherapeutic agents to contest such malignancies. This review will also be useful in the chemotherapeutic agent development by providing crucial information about such hematological malignancy-related proteins and their inhibitors. The repurposed drugs with potential for anticancer applications are also discussed.

Summary: Increasing evidence has shown that lncRNAs contribute considerably to modulate autophagy in the context of CVDs. In this review, we first summarize the current knowledge of the role lncRNAs play in cardiovascular autophagy and autophagy-involved CVDs. Then, recent developments of antisense oligonucleotides (ASOs) designed to target lncRNAs to specifically modulate autophagy in diseased hearts and vessels are discussed, focusing primarily on structure-activity relationships of distinct chemical modifications and relevant clinical trials.

Perspective: ASOs are promising in cardiovascular drug innovation. We hope that future studies of lncRNA-based therapies would overcome existing technical limitations and help people who suffer from autophagy-involved CVDs.

Objective: This review covers the recent synthesis and pharmacological advancement of dihydropyrimidinones/ thiones moiety, along with covering the structure-activity relationship of the most potent compounds, which may prove to become better, more efficacious and safer agents. Thus, this review may help the researchers in drug designing and development of new Dihydropyrimidinones entities.

Conclusion: This review focuses on the wide application of dihydropyrimidinone/thione review reports the design, synthesis and pharmacological activities of nitrogen-sulphur containing dihydropyrimidinone moiety by using multi-component reaction. Dihydropyrimidinones (DHPM) pharmacophore is an important heterocyclic ring in medicinal chemistry. It is derived from multi-component reactions, “Biginelli reaction” and plays a critical role as anticancer, antioxidant, antimicrobial, anti-inflammatory, anti-HIV-1, antimalarial, anti-inflammatory, antihypertensive and anti-tubercular agents. Exhaustive research has led to its vast biological profile, with a wide range of therapeutic application.

Objective: Therapeutic options for chronic HCV infection have evolved dramatically since 2014, with a translation from pegylated interferon and ribavirin (associated with suboptimal cure and high treatment-related toxicity) to oral direct-acting antiviral treatment. There are four classes of direct-acting antivirals which differ by their mechanism of action and therapeutic target. They are all pointed to proteins that form the cytoplasmic viral replication complex. Multiple studies have demonstrated that direct-acting antiviral therapy is extremely well tolerated, highly efficacious, with few side effects.

Methods: We performed an indexed MEDLINE search with keywords regarding specific direct-acting antiviral regimes and their pharmacokinetics, drug-drug interactions, and metabolism in specific settings of pregnancy, lactation, liver cirrhosis, liver transplantation and HCC risk, kidney failure and kidney transplantation.

Results: We present a comprehensive overview of specific direct-acting antiviral metabolism and drug-drug interaction issues in different settings.

Conclusion: Despite its complex pharmacokinetics and the possibility of drug-drug interactions, direct-acting antivirals are highly efficacious in providing viral clearance, which is an obvious advantage compared to possible interactions or side effects. They should be administered cautiously in patients with other comorbidities, and with tight control of immunosuppressive therapy.

Methods: The association between glycemic dysregulation and health outcomes for inpatients with diabetes was systematically reviewed. PubMed, Embase, and LILACS databases were searched. Two independent reviewers were involved in each of the following steps: screening titles, abstracts, and fulltexts; assessing the methodological quality; and extracting data from included reviews. Descriptive analysis method was used.

Results: Seven cohort studies were included, and only two had a prospective design, consisting of 7,174 hospitalized patients with diabetes. In-hospital occurrence of hypoglycemia, hyperglycemia, and glycemic variability were assessed, and outcomes were mortality, infections, renal complications, and adverse events. Among the exposure and outcomes, an association was observed between severe hypoglycemia and mortality, hyperglycemia and infection, and hyperglycemia and adverse events.

Conclusion: In-hospital uncontrolled glycemia in patients with diabetes is associated with poor health outcomes. More studies should be conducted for proper investigation because diabetes is a complex condition. Effects of glycemic dysregulation should be investigated on the basis of overall health of a patient instead from only organ-target perspective, which makes the investigation difficult.]]> https://www.benthamscience.comarticle/110628Background: The fibroblast growth factor (FGF) family is comprised of 23 highly regulated monomeric proteins that regulate a plethora of developmental and pathophysiological processes, including tissue repair, wound healing, angiogenesis, and embryonic development. Binding of FGF to fibroblast growth factor receptor (FGFR), a tyrosine kinase receptor, is facilitated by a glycosaminoglycan, heparin. Activated FGFRs phosphorylate the tyrosine kinase residues that mediate induction of downstream signaling pathways, such as RAS-MAPK, PI3K-AKT, PLCγ, and STAT. Dysregulation of the FGF/FGFR signaling occurs frequently in cancer due to gene amplification, FGF activating mutations, chromosomal rearrangements, integration, and oncogenic fusions. Aberrant FGFR signaling also affects organogenesis, embryonic development, tissue homeostasis, and has been associated with cell proliferation, angiogenesis, cancer, and other pathophysiological changes.

Objective: This comprehensive review will discuss the biology, chemistry, and functions of FGFs, and its current applications toward wound healing, diabetes, repair and regeneration of tissues, and fatty liver diseases. In addition, specific aberrations in FGFR signaling and drugs that target FGFR and aid in mitigating various disorders, such as cancer, are also discussed in detail.

Conclusion: Inhibitors of FGFR signaling are promising drugs in the treatment of several types of cancers. The clinical benefits of FGF/FGFR targeting therapies are impeded due to the activation of other RTK signaling mechanisms or due to the mutations that abolish the drug inhibitory activity on FGFR. Thus, the development of drugs with a different mechanism of action for FGF/FGFR targeting therapies is the recent focus of several preclinical and clinical studies.

Objective: This work aims to fully review the state-of-the-art regarding pathophysiology, diagnosis, treatment, and other relevant clinical and forensic features of pharmacobezoars.

Results: Patients of a wide range of ages and of both sexes present with signs and symptoms of intoxications or more commonly gastrointestinal obstructions. The exact mechanisms of pharmacobezoar formation are unknown but are likely multifactorial. The diagnosis and treatment depend on the gastrointestinal segment affected and should be personalized to the medication and the underlying factor. A good and complete history, physical examination, image tests, upper endoscopy, and surgery through laparotomy of the lower tract are useful for diagnosis and treatment.

Conclusion: Pharmacobezoars are rarely seen in clinical and forensic practice. They are related to controlled or immediate-release formulations, liquid, or non-digestible substances, in normal or altered digestive motility/anatomy tract, and in overdoses or therapeutic doses, and should be suspected in the presence of risk factors or patients taking drugs which may form pharmacobezoars.

Methods: This literature-based review focuses on metabolism-based DDIs, the most prevalent DDIs responsible for difficulties in therapeutic management in patients with CRDs.

Results: Clinically relevant metabolism-based DDIs occur between drugs used for the treatment of respiratory diseases (corticosteroids, orally inhaled bronchodilators, methylxanthines, anti-leukotrienes, antimicrobials, endothelin receptor antagonists, phosphodiesterase inhibitors, antitussives, and antineoplastic agents) and drugs affecting cytochrome P450 (CYP) (inducers and inhibitors). Considering alternative therapies, adjusting medication doses, or monitoring patients during treatment are recommended to prevent the harmful consequences of these interactions.

Conclusion: Providing information on clinically relevant interactions of drugs more likely prescribed in daily practices of physicians is essential to improve patient safety. A list of known metabolism-based interactions of drugs affecting the respiratory systems should be available for physicians engaged in the treatment of CRDs.

Objective: The CSC hypothesis, cellular therapy, and the most recent patents on CSCs were reviewed.

Methods: PubMed, Scopus, and Google Scholar were screened for this information. Also, an analysis of the most recent data targeting CSCs in pediatric cancer developed at two Canadian institutions is provided. The genes involved with the activation of CSCs and the drugs used to antagonize them are also highlighted.

Results: It is underlined that (1) CSCs possess stem cell-like properties, including the ability for self-renewal; (2) CSCs can start carcinogenesis and are responsible for tumor recurrence after treatment; (3) Although some limitations have been raised, which may oppose the CSC hypothesis, cancer progression and metastasis have been recognized to be caused by CSCs.

Conclusion: The significant roles of cell therapy may include an auto-transplant with high-dose treatment, an improvement of the immune function, creation of chimeric antigen receptor T cells, and the recruitment of NK cell-based immunotherapy.

Objective: The number of drugs being used in chemotherapy has heterocycles as their basic structure in spite of various side effects. Medicinal chemists are focusing on nitrogen-containing heterocyclic compounds like pyrrole, pyrrolidine, pyridine, imidazole, pyrimidines, pyrazole, indole, quinoline, oxadiazole, azole, benzimidazole, etc. as the key building blocks to develop active biological compounds. The aim of this study is to attempt to compile a dataset of nitrogen-containing heterocyclic anti-cancer drugs.

Methods: We adopted a structural search on notorious journal publication websites and electronic databases such as Bentham Science, Science Direct, PubMed, Scopus, USFDA, etc. for the collection of peer-reviewed research and review articles for the present review. The quality papers were retrieved, studied, categorized into different sections, analyzed and used for article writing.

Conclusion: As per FDA databases, nitrogen-based heterocycles in the drug design are almost 60% of unique small-molecule drugs. Some of the nitrogen-containing heterocyclic anti-cancer drugs are Axitinib, Bosutinib, Cediranib, Dasatanib (Sprycel®), Erlotinib (Tarceva®), Gefitinib (Iressa®), Imatinib (Gleevec®), Lapatinib (Tykerb ®), Linifanib, Sorafenib (Nexavar®), Sunitinib (Sutent®), Tivozanib, etc. In the present review, we shall focus on the overview of nitrogen-containing heterocyclic active compounds as anti-cancer agents.

Objective: To evaluate the efficacy, safety and possible future directions of anti-VEGF agents used for the treatment of CNV owing to different aetiologies.

Methods: A computerized search of articles dealing with the topic of anti-VEGF therapy in CN was conducted in PubMed, Scopus and Medline electronic databases. The following key phrases were used: anti-VEGF agents, corneal neovascularization, bevacizumab, ranibizumab, vascular endothelial growth factor, angiogenesis.

Results: The use of anti-VEGF therapy in the treatment of CN reduced pathological vessel density without causing significant side effects. Various administration routes such as topical, subconjunctival and intrastromal ones are available, and the choice depends on patient and disease characteristics. Much more effectiveness is achieved in case of early administration before mature and wellestablished vessels take place. A combined approach between various drugs including anti-VEGF agents should be adopted in those cases at higher risk of neovascularization recurrence such as chronic long-standing diseases where ischemic and inflammatory stimuli are not definitively reversed.

Conclusion: The efficacy and safety of anti-VEGF agents support their adoption into the daily clinical practice for the management of CN.

Objective: The anti-diabetic effects of β -glucan from Aureobasidium pullulans were assessed in a streptozotocin (STZ)-induced rat diabetes model at 62.5 and 125 mg/kg doses. In addition, the possibility of changes in the effects of β-glucan according to the severity of diabetes was also assessed at one dosage (62.5 mg/kg): severe, >360 mg/dL; slight, 130-200 mg/dL.

Methods: Test articles were administered orally to STZ-induced diabetic rats from 21 days after STZ dosing for 4 weeks. Each of five or six female rats per group was selected using blood glucose levels at 21 days after STZ dosing. Changes in body weight were recorded during the study, along with blood glucose, blood urea nitrogen, creatinine, and serum aspartate aminotransferase and alanine aminotransferase levels. On the day of sacrifice, livers and kidneys were weighed and observed microscopically for changes in the percentage of degenerative regions and numbers of degenerative tubules in the kidney.

Results: β-glucan showed no hypoglycemic effects in the STZ-induced diabetic rat model. However, it had favorable effects on decreasing diabetic complications related to diabetic nephropathy and hepatopathy.

Conclusion: Based on the results of this study, it was concluded that β-glucan showed favorable effects in decreasing diabetic complications in STZ-induced rat diabetes model.

Introduction: The SGLT2 inhibitors by inhibiting the SGLT2 in the proximal nephron, helps in reducing the reabsorption of approximately 90% of the filtered glucose and increased urinary glucose excretion (UGE).

Methods: The literature related to SGLT2 inhibitors has been thoroughly explored from various available public domains and reviewed extensively for this article. Detailed and updated information related to SGLT2 inhibitors with a major focus on the recently approved Ertuglifolzin is structured in this review.

Result: The present review is an effort to understand the management of diabetes mellitus over the past few decades with a special focus on the role of SGLT2 receptor in the causes of therapeutic and preventive strategies for diabetes mellitus. Pragmatic placement of the currently available Canagliflozin, Dapagliflozin, and Empagliflozin as oral antidiabetic agents has been done. Well accommodated stereochemistry and a high docking score of Ertugliflozin in ligand-receptor simulation studies attribute to its high potency.

Conclusion: This review highlights the unique mechanism of SGLT2 Inhibitors coupled with pleiotropic benefits on weight and blood pressure, which make it an attractive choice of therapy to diabetic patients, not controlled by other medications.

Objective: This study aimed to explore the effect of mannitol on spinal cord edema after SCI in rats.

Methods: Seventy-eight adult female rats were assigned to three groups randomly: a sham control group (n = 18), a contusion and normal saline contrast group (n=30), and a contusion and mannitol treatment group (n=30). We used the open-field test to estimate the functional recovery of rats weekly. Spinal cord water content was measured to determine the spinal cord edema. The ultrastructure features of the injured dorsolateral spinal cord were determined on the 7th day after SCI by HE staining.

Results: The mannitol group had greatly improved Basso-Beattie-Bresnahan (BBB) scores when compared with the saline contrast group. The spinal cord water content was increased significantly after SCI, and there was no significant difference in the water content between the NaCl and mannitol groups 1 day after SCI. The water content at 3 and 7 days after SCI was significantly lower in the mannitol group than in the NaCl group (p < 0.05). Mannitol can reduce spinal cord edema by increasing the number of red blood cells in the injured spinal cord and decrease the ratio (dorsoventral diameter/ mediolateral diameter) of spinal cord 7 days post-SCI.

Conclusion: Mannitol increases recovery of motor function in rats, reduces spinal cord edema and increases the number of red blood cells in the injured spinal cord, decreasing the ratio of spinal cord to reduce pressure.