Serum LDH Levels Research Articles

Preventive effect of imperatorin against doxorubicin-induced cardiotoxicity through suppression of NLRP3 inflammasome activation.

Cardiotoxicity is one of the major obstacles to anthracycline chemotherapy. Anthracycline cardiotoxicity is closely associated with inflammation. Imperatorin (IMP), a furocoumarin ingredient extracted from Angelica dahurica, might have potential activity in preventing anthracycline cardiotoxicity due to its anti-cancer, anti-inflammatory, anti-oxidant, cardioprotective properties. This study aims to reveal the effect of IMP on doxorubicin (DOX)-induced cardiotoxicity and its underlying mechanism. We established a rat model of DOX-induced cardiotoxicity by intraperitoneal injection with DOX (1.25mg/kg twice weekly for 6weeks), and found that both IMP (25mg/kg and 12.5mg/kg) and dexrazoxane 12.5mg/kg relieved DOX-induced reductions in heart weight, change in cardiac histopathology, and elevated serum levels of LDH, AST and CK-MB. Moreover, DOX upregulated mRNA levels of NLRP3, CASP1, GSDMD, ASC, IL-1β and IL-18, elevated protein expressions of NLRP3, ASC, GSDMD-FL, GSDMD-N, pro‑caspase‑1, caspase‑1 p20, pro‑IL‑1β and IL‑1β in heart tissues, as well as increased serum levels of pro-inflammatory cytokines including IL-1β and IL-18, however both of IMP and dexrazoxane suppressed these alterations. In addition, we carried out neonatal rat cardiomyocytes experiments to confirm the results of the in vivo study. Consistently, pretreatment with IMP 25µg/mL relieved DOX (1μg/mL)-induced cardiomyocytes injury, including decreased cell viability and reduced supernatant LDH. IMP inhibited DOX-induced activation of NLRP3 inflammasome in cardiomyocytes. In conclusion, IMP had a protective effect against DOX-induced cardiotoxicity via repressing the activation of NLRP3 inflammasome. These findings suggest that IMP may be a promising alternative or adjunctive drug for the prevention of anthracycline cardiotoxicity.

The Activation of PKM2 Induces Pyroptosis in Hippocampal Neurons via the NLRP3/Caspase-1/GSDMD Pathway in Neonatal Rats With Hypoxic-Ischemic Brain Injury.

The presence of hypoxic-ischemic brain damage (HIBD) in neonates triggers a strong neuroinflammatory reaction. Pyroptosis, a programmed cell death mechanism associated with inflammation, plays a crucial role in HIBD. Pyruvate kinase M2 (PKM2) plays a significant role in connecting metabolic processes and inflammatory responses, but whether it affects hippocampus pyroptosis in HIBD is unclear. The aim of this study is to elucidate the role of PKM2 in HIBD and to propose a novel therapeutic approach for neonatal ischemic-hypoxic encephalopathy. In this study, we employed neonatal 7-day-old Sprague Dawley rats to establish a model of HIBD using the Rice-Vannucci surgical technique and a hypoxia device. To inhibit the elevation of PKM2, we utilized the PKM2 inhibitor shikonin. The rats were categorized into four groups: Sham, Shikonin, HIBD, and Shikonin+HIBD. Behavioral tests, hematoxylin eosin staining, immunofluorescence staining, ELISA (IL-1β, IL-18), and LDH were conducted in each group to evaluate neurological function, hippocampal damage, the occurrence of neuronal pyroptosis, and the neuroinflammation. Western blot was used to assess the expression levels of PKM2, NLRP3, Caspase-1, Cleaved Caspase-1, GSDMD, GSDMDN, and IL-1β. The expression of PKM2 elevated in hippocampal tissues of the HIBD model and the localization of PKM2 in the hippocampus was activated in neurons instead of microglia during the HIBD. Meanwhile, the inhibition of PKM2 improved the behavioral test scores and the body weight of rats, the neuronal damage in the CA1 region of hippocampal tissue was also attenuated. In addition, inhibiting PKM2 alleviated neuronal pyroptosis by decreasing the expression of PKM2, NLRP3, Caspase-1, Cleaved Caspase-1, GSDMD, GSDMDN. Furthermore, serum levels of LDH and inflammatory factors IL-1β and IL-18 decrease with PKM2 inhibition. Based on these findings, we can conclude that PKM2 plays a crucial role in regulating hippocampal neuronal pyroptosis of HIBD rats via NLRP3/Caspase-1/GSDMD pathway. Therefore, inhibiting PKM2 could be a promising therapeutic strategy for the treatment of neonatal ischemic-hypoxic encephalopathy.

Association between laboratory markers, clinical and radiological findings in patients with idiopathic intracranial hypertension: case–control study

BackgroundIdiopathic intracranial hypertension (IIH) is a disease of raised intracranial pressure. Contribution of inflammatory mediators has been suggested in IIH pathophysiology. The aim of this study was to estimate certain serum inflammatory markers in IIH patients compared to normal subjects. Also, to examine the correlation between these laboratory parameters and the clinical and radiological characteristics of IIH patients.ResultsBody mass index (BMI) was significantly higher among IIH patients compared to controls. Serum LDH, CRP, NLR and PLR were significantly higher, whereas serum iron was significantly lower in IIH patients compared to healthy controls. IIH patients with stenosis in brain MRV had significantly higher mean serum CRP compared with patients with normal MRV. There was a statistically significant positive correlation between serum CRP and the presence of stenosis in MRV, between serum LDH level and grade of papilledema, and between CRP, TIBC, and NLR with BMI.ConclusionsThere is a significant elevation of inflammatory markers in IIH patients. Moreover, cerebral venous sinus stenosis and BMI were positively associated with higher markers of inflammation as CRP, LDH and NLR indicating the role of inflammation in thrombosis and obesity associated with IIH.

4-Phenylbutyric acid suppresses psoralen-induced hepatotoxicity by inhibiting ERS and reestablishing mitochondrial fusion-fission balance in mice

Psoralen is a main active molecule of the traditional Chinese herb medicine Fructus Psoraleae. Our previous studies have shown that psoralen induced liver injury through the endoplasmic reticulum stress (ERS) signaling pathways. In this article, we studied whether the ERS inhibitor, 4-phenylbutyrate acid (4-PBA) could inhibit the liver toxicity caused by psoralen, and explored the underlying mechanisms. Mice were given the solvent, 20 mg/kg, 40 mg/kg, 80 mg/kg of psoralen, or 80 mg/kg of psoralen plus 4-PBA for 14 days. We found that 4-PBA significantly reduced the serum LDH and liver tissue MDA level, increased the activities of SOD and CAT, reduced liver weight and coefficient, repaired histopathological damage, and inhibited hepatocytes apoptosis induced by psoralen. RNA-seq transcriptomics found that except for the endoplasmic reticulum, the mitochondria was severely affected by psoralen. And genes involved in mitochondrial fusion, apoptosis, protein folding, and autophagy were found differently expressed in the psoralen group. Further studies found that 4-PBA inhibited the overexpression of GRP78 and CHOP, increased the Bcl-2/Bax ratio, and reduced the expression of Caspase-3. Moreover, 4-PBA reduced the overexpression of mitochondrial fission protein DRP1, increased the expression of fusion proteins Mfn-2 and OPA1, but has no inhibitory effects on autophagy proteins Atg5 or LC3A/B. In conclusion, 4-PBA inhibited ERS and reestablished mitochondrial fusion-fission balance, thereby blocking cell apoptosis, oxidative stress, and mitochondrial dysfunction, thus prevented against psoralen-induced hepatotoxicity.

Possibility of maintaining remission with topical therapy alone after withdrawal of dupilumab in Japanese patients with atopic dermatitis and their characteristics in the real world.

Psossibility and appropriate timing of discontinuation of dupilumab for atopic dermatitis (AD) remain unclear. We explored the possibility of patients, who could maintain remission with topical therapy alone after withdrawing dupilumab in the real world. Furthermore, we identified their characteristics. All adult AD patients who initiated dupilumab from June 2018 to July 2022 and were treated with dupilumab for more than 3 months at our hospital were included in this study. The observation period was from June 2018 to July 2023. In 138 patients, 58 (42.0%) discontinued dupilumab at least once. Among them, 18 (13.0%) discontinued dupilumab but reinitiated dupilumab later due to exacerbation. Only seven patients (5.1%) could maintain remission with topical therapy alone after discontinuation of dupilumab, with characteristics of lower POEM, VAS of pruritus, serum levels of TARC and LDH, and neutrophil counts at baseline, and those of longer duration of dupilumab until its discontinuation (24.0 ± 13.3 vs. 12.8 ± 7.3 months) and lower EASI and affected BSA at the discontinuation of dupilumab. In 118 patients treated with dupilumab for at least 1 year, 38 patients (32.2%) discontinued at least once. Only four patients (3.4%) could maintain remission with topical therapy alone after discontinuation of dupilumab, with characteristics of lower POEM at baseline and lower EASI at the discontinuation of dupilumab. In conclusion, maintaining remission after withdrawing dupilumab is challenging. Discontinuation of dupilumab may be considered in patients with low baseline POEM, after more than 2 years of dupilumab treatment, with a substantial decrease in EASI.

Prognostic Role of Clinicopathological Characteristics and Serum Markers in Metastatic Melanoma Patients Treated with BRAF and MEK Inhibitors.

A total of 199 patients with advanced melanoma treated with BRAF + MEK inhibitors were included in our single-center retrospective study. We analyzed the risk of progression and death using multivariate Cox proportional hazard models. The predictive effect of prognostic factors on progression-free survival (PFS) was evaluated in ROC analysis. We found that primary tumor localization, Clark level, pT category, baseline M stage and baseline serum S100B are independent and significant prognostic factors for PFS. The discriminative power of the combination of these factors was excellent for predicting 18 month PFS (AUC 0.822 [95% CI 0.727; 0.916], p < 0.001). Primary tumor localization on the extremities, Clark level V, baseline M1c stage or M1d stage, and elevated baseline serum S100B and LDH levels were independently and significantly associated with unfavorable overall survival (OS). Baseline M stage and serum S100B appear to be independent prognostic factors for both PFS and OS in melanoma patients treated with BRAF + MEK inhibitors. We newly identified significant and independent prognostic effects of primary tumor localization and Clark level on survival that warrant further investigation.

Impact of JAK2 V617F mutation on disease profile and prognostic risk factors in primary myelofibrosis (MPN) - A tertiary care experience.

Objective: To evaluate the association between JAK2 mutation status, PMF disease characteristics, and prognostic features as assessed by the DIPSS Plus scoring system. We analyzed clinical and laboratory data from a cohort of PMF patients to determine the influence of JAK2 mutation on disease presentation and progression. Study Design: Cross Sectional study. Setting: Department of Pathology and Oncology, King Edward Medical University/Mayo Hospital, Lahore. Period: December 2022 to December 2023. Methods: Total 27 patients with PMF were enrolled in the study by non-probability consecutive sampling technique. Patients were diagnosed according to WHO 2016 criteria. CBC and serum LDH were performed by automated hematology and chemistry analyzers respectively. Real-time PCR was used to identify the JAK2 mutations. Risk stratification was done by DIPPS criteria. Data was analyzed by Microsoft Excel 2010. Mean and standard deviation was calculated. Student ‘T’ test was used for comparison of mean between two groups with and without JAK2 mutations. Results: Out of 27 patients 66.6% were males and median age was 59 years. Splenomegaly was the dominant clinical feature accounting for 51.4% with mean splenic span of 17.8±2.91cm. Mean LDH levels was 872.5±324. JAK2 positive expression was found to be significantly correlated with increased splenic span and raised LDH levels with P-value of &lt;0.05. Risk stratification showed 11% patients were in high-risk group. Conclusion: Marked enlargement of spleen and raised in serum LDH levels indicate that patients in our settings had clinically advanced stage of the disease. Apart from this manifestation of JAK2 V617F mutated patients indicated a more aggressive phenotype of the disease.

Female Patients with Small Cell Lung Cancer Have Better Survival than Males with Extensive but Not Limited Disease

Introduction: Several previous studies have explored whether sex has prognostic significance in patients with small cell lung cancer (SCLC). In this retrospective study, we aimed to show the clinical significance of sex in SCLC patients. Methods: A total of 378 SCLC patients were assessed retrospectively. Results: Sixty-one (16.1%) patients were women; 26 of 131 (19.9%) patients had limited disease (LD-SCLC); and 14.2% of patients (35 of 247 patients) had extended disease (ED-SCLC). In all SCLC patients, regardless of stage, female patients were more likely to be nonsmokers (7.7 vs. 1%, p = 0.04 for LD-SCLC; and 11.4 vs. 1.4%, p = 0.001 for ED-SCLC) and more often to be anemic (26.9 vs. 11.4%, p = 0.04 for LD-SCLC; and 45.7 vs. 28%, p = 0.03 for ED-SCLC). While women with LD-SCLC were diagnosed younger (<60) than men (65.4 vs. 37.1%, p = 0.009), they had larger (>5 cm) tumors (69.2 vs. 42.9%, p = 0.01). Moreover, obesity (77.1 vs. 56.4%, p = 0.02) and less weight loss (88.6 vs. 73.6%, p = 0.04) were more common in women with ED-SCLC than in men. However, there were no associations between sex and significant prognostic factors, such as performance status, metastasis site, serum LDH level, response to chemotherapy, and disease recurrence. Outcomes in LD-SCLC patients were found to be similar between sexes; median overall survivals in women compared to men was 18 versus 15 months, respectively (p = 0.8). On the other hand, female patients with ED-SCLC had better survivals; median survivals for women versus men were 10 versus 7 months, respectively (p = 0.008). This significance for female ED-SCLC patients was also maintained in the multivariate analysis (p = 0.001). Conclusion: While the survival rates of female patients, who constitute a small proportion of SCLC patients, are no different from men in LD-SCLC, they are better in ED-SCLC.

Compound Yuye Decoction protects diabetic rats against cardiomyopathy by inhibiting myocardial apoptosis and inflammation via regulating the PI3K/Akt signaling pathway

To explore the therapeutic mechanism of compound Yuye Decoction against diabetic cardiomyopathy (DCM). Drugbank, Gene Cards, OMIM and PharmGKb databases were used to obtain DCM-related targets, and the core targets were identified and functionally annotated by protein-protein interaction network analysis followed by GO and KEGG enrichment analysis. The "Traditional Chinese Medicine-Key Component-Key Target-Key Pathway" network was constructed using Cytoscape 3.9.1, and molecular docking was carried out for the key components and the core targets. In the animal experiment, Wistar rat models of DCM were treated with normal saline or Yuye Decoction by gavage at low (0.29 g/kg) and high (1.15 g/kg) doses for 8 weeks, and the changes in cardiac electrophysiology and histopathology were evaluated. The changes in serum levels of LDH, CK, and CK-MB were examined, and myocardial expressions of PI3K, P-PI3K, Akt, P-AKT, BAX, IL-6, and TNF-α were detected using Western blotting. We identified 61 active compounds in Yuye Decoction with 1057 targets, 3682 DCM-related disease targets, and 551 common targets between them. Enrichment of the core targets suggested that apoptosis, inflammation and the PI3K/Akt pathways were the key signaling pathways for DCM treatment. Molecular docking studies showed that the active components in Yuye Decoction including gold amidohydroxyethyl ester and kaempferol had strong binding activities with AKT1 and PIK3R1. In DCM rat models, treatment with Yuye Decoction significantly alleviated myocardial pathologies, reduced serum levels of LDH, CK and CK-MB, lowered myocardial expressions of BAX, IL-6 and TNF-α, and increased the expressions of P-PI3K and P-AKT. The therapeutic effect of compound Yuye Decoction against DCM is mediated by its multiple active components that act on multiple targets and pathways to inhibit cardiomyocyte apoptosis and inflammatory response by regulating the PI3K/Akt signaling pathway.

The therapeutic effect of NRF2 activator, ezetimibe, in cardiac cachexia.

Heart failure (HF) is caused by functional and structural irregularity leading to impaired ejection or filling capacity of the heart. HF leads to chronic inflammatory conditions in the heart leads to weight loss, anorexia, and muscle atrophy known as cachexia. The present study was carried out to investigate the role of Ezetimibe, an NRF2 activator, in cardiac cachexia and to develop a treatment strategy for cardiac cachexia. Balb/c mice of either sex at 6-8 weeks of age were given 2 mg/kg of doxorubicin in 0.9% sodium chloride solution intraperitoneally (i.p.) for the alternate days for the first week and then once a week for the next 4 weeks. After induction of cardiac atrophy, treatment with Ezetimibe (1.5 mg/kg, p.o) was given for the next 4 weeks. In the cardiac cachectic animals, a significant decrease in body weight, food, and water intake was observed. Cardiac cachectic animals showed a significant increase in serum glucose, total cholesterol, LDL, triglyceride, VLDL, CK-MB, LDH, and CRP levels. Cardiac atrophic index, heart weight to body weight ratios (HW/BW), right ventricular weight to heart weight ratios (RV/HW), and left ventricular weight to heart weight ratios (LV/HW), were significantly decreased in cardiac cachectic animals. The weights of the skeletal muscles such as EDL, gastrocnemius, soleus, tibialis anterior, and quadriceps muscles, and the weight of adipose tissue such as subcutaneous, visceral, perirenal, and brown adipose tissue were significantly decreased in the cardiac cachectic group relative to the normal group. Treatment with ezetimibe improves body weight, food intake, and water intake. Ezetimibe decreases serum glucose, total cholesterol, LDL, triglyceride, VLDL, CK-MB, LDH and CRP levels. Cardiac atrophic markers such as HW/BW, RV/HW, and LV/HW were improved. The weight of skeletal muscles and adipose tissue was increased after treatment with ezetimibe. Our data showed that the NRF2 activator, Ezetimibe produces a beneficial effect on cardiac cachexia in the doxorubicin-induced cardiac cachexia model. Ezetimibe was successful to reduce the levels of inflammatory cytokines, ameliorate the effects on cardiac muscle wasting, lipid levels, fat tissues, and skeletal muscles.

Exosomes of mesenchymal stem cells and PRP restore spermatogenesis in the rat model of non-obstructive azoospermia.

Since available therapeutic approaches for chemotherapy-induced non-obstructive azoospermia (NOA) patients are not enough efficient, an urgent need for treatment alternatives is felt. This study shows that adipose tissue-derived mesenchymal stem cells-derived exosome (AD-Exo) treatment is more effective in ameliorating busulfan-induced NOA rat models compared to platelet-rich plasma (PRP). Patients with non-obstructive azoospermia (NOA) are unable to have their children. Therefore, there is an urgent need for additional treatment alternatives for these patients. Recently, novel treatments based on the exosomes derived from mesenchymal stem cells (MSCs) as the agents responsible for exerting the paracrine effects and consequently biological functions of MSCs are proposed. Besides, platelet-rich plasma (PRP) as a significant blood byproduct has been therapeutically applied in several male infertility studies. In this study, we compared the effects of PRP and exosome treatment on spermatogenesis restoration in NOA rat models. Exosomes and PRP were isolated from the adipose tissue-derived MSCs (AD-MSCs) collected from conditioned medium and peripheral blood of human volunteers, respectively. Non-obstructive azoospermia (NOA) induction was done through two doses of busulfan at a 21-day interval. Thirty-five days after NOA induction, intratesticular injection of AD-MSCs-derived exosome (AD-Exo), PRP, and PBS was performed. The control group did not receive any treatment. Two months later, the rats were euthanized for further analysis. Our results revealed that both AD-Exo and PRP treatments improved the size and weight of testis, modulated the expression level of Dazl, Ddx4, Stra8, Pwil1, and Ccna1, and ameliorated the serum level of LDH, SOD, and GR enzymes in NOA rats. Moreover, the AD-Exo group showed improved testosterone, GPx, MAD, and CAT serum levels, sperm motility, and protein levels of DAZL and DDX4. This investigation verified the more efficient effects of AD-Exo treatment in comparison to PRP in ameliorating busulfan-induced NOA rat models.

Deletion of Dux ameliorates muscular dystrophy in mdx mice by attenuating oxidative stress via Nrf2.

DUX4 has been widely reported in facioscapulohumeral muscular dystrophy, but its role in Duchenne muscular dystrophy (DMD) is unclear. Dux is the mouse paralog of DUX4. In Dux-/- mdx mice, forelimb grip strength test and treadmill test were performed, and extensor digitorum longus (EDL) contraction properties were measured to assess skeletal muscle function. Pathological changes in mice were determined by serum CK and LDH levels and muscle Masson staining. Inflammatory factors, oxidative stress, and mitochondrial function indicators were detected using kits. Primary muscle satellite cells were isolated, and the antioxidant molecule Nrf2 was detected. MTT assay and Edu assay were used to evaluate proliferation and TUNEL assay for cell death. The results show that the deletion of Dux enhanced forelimb grip strength and EDL contractility, prolonged running time and distance in mdx mice. Deleting Dux also attenuated muscle fibrosis, inflammation, oxidative stress, and mitochondrial dysfunction in mdx mice. Furthermore, Dux deficiency promoted proliferation and survival of muscle satellite cells by increasing Nrf2 levels in mdx mice.

Rutin mitigates acetic acid-induced ulcerative colitis: novel coloprotective mechanism.

Ulcerative colitis, an inflammatory bowel disease, is characterized by a status of oxidative stress and inflammation. Rutin is a natural flavonoid with many pharmacological activities and its role in acetic acid-induced ulcerative colitis through the high mobility group B1 (HMGB1)/ toll-like receptor-4 (TLR4)/ myeloid differentiation primary response protein 88 (MYD88)/ nuclear factor-kB (NF-kB) signaling pathway needs to be explored. Four experimental groups were divided into control group, rutin group: treated with 100mg/kg/day rutin orally for 10days, acetic acid (AA) group: given intracolonic instillation of AA to induce ulcerative colitis, and acetic acid with rutin treatment (AA/Rutin) group. Acetic acid caused a marked increase in the colon weight/length ratio and induced colonic histopathological changes, leading to a marked rise in the colonic histopathological scores. Acetic acid exhibited a significant rise in LDH and CRP serum levels as well as TOS colonic levels, accompanied by a marked decline in TAS colonic contents compared to the control group. Moreover, AA-induced activation of the HMGB1/TLR4/MYD88/NF-kB signaling pathway. Rutin demonstrated a significant decrease in the colon weight/length ratio, ameliorated the colonic histopathological changes induced by AA, and exhibited a marked decline in the colonic histopathological scores. Rutin showed a significant decrease in serum LDH, and CRP levels as well as colonic TOS contents when compared with the AA group. Rutin suppressed the colonic activation of the HMGB1/TLR4/MYD88/NF-kB signaling pathway. Rutin could be a promising coloprotective agent against AA-induced ulcerative colitis by targeting the HMGB1/TLR4/MYD88/NF-kB signaling pathway.

The serum LDH level and KELIM scores are potential predictors of a benefit from bevacizumab first-line therapy for patients with advanced ovarian cancer.

The survival benefit of first-line treatment with bevacizumab in advanced ovarian cancer patients are multifaceted. In our study, we aimed to identify potential markers of bevacizumab efficacy to help predict which patients would experience survival benefits. This was a retrospective analysis of 114 patients examined from January 1, 2015, to March 1, 2023, and data on clinical, biological, and imaging variables, such as ascites, serum LDH, and CA125, were extracted from electronic medical records. We performed a correlation analysis and principal component analysis to investigate correlations among variables and reduce their dimensionality. Then, univariate and multivariate Cox proportional hazards regression analyses were used to identify the predictors of progression-free survival. Favorable KELIM score (≥ 1, HR 0.376, 95% CI [0.202-0.700], p = 0.002), which indicated better chemosensitivity, and lower LDH levels (≤ 210 U/L, HR 38.73, 95% CI [6.108-245.6], p < 0.001) were found to be independent predictors of a treatment benefit with bevacizumab in patients with advanced ovarian cancer. Regardless of LDH level, patients with favorable KELIM scores had a higher progression-free survival (PFS) benefit (p = 0.18). Among patients with unfavorable KELIM scores, those with higher LDH levels had the lowest PFS benefit (median: 11.5months, p = 0.0059). Patients with poor chemosensitivity and low LDH levels are more likely to benefit from first-line bevacizumab treatment. The combination of the two markers can be a helpful predictor of patients who are most likely to benefit from treatment and a guide for treatment decisions-making. Retrospectively registered: 2020-MD-371, 2020.10.12.

Examinatıon of D-Dimer, Fibrınogen, CRP, and LDH Levels in Serum of Patients with COVID-19 Diabetes Mellitus

Examinatıon of D-Dimer, Fibrınogen, CRP, and LDH Levels in Serum of Patients with COVID-19 Diabetes Mellitus

Effect of Lignocaine on Postoperative Serum Lactate Dehydrogenase and Lactate Levels in Patients Undergoing Bowel Surgery

Objective: To evaluate effect of intraoperative lignocaine on postoperative serum LDH and lactate levels and to compare with placebo in patients undergoing bowel surgery. Methodology: This randomized controlled trial was conducted at the Department of Biochemistry, Islam Medical, Sialkot, Pakistan from August 2023 to January 2024. Serum LDH and lactate levels were measured preoperatively on automatic biochemical analyzer (produced by Beckman Coulter, GRM, 2166) was used to analyze, before extubation, and at 6 and 24 hours postoperatively, between patients who received intraoperative lignocaine versus those who received saline during bowel surgery under general anesthesia. Results: The study involved two groups: Group lignocaine (n = 20) where patients received 2% lignocaine at the rate of 1.5 mg/kg intravenous followed by maintenance infusion at the same rate until the end of surgery, and Group normal saline (n = 20) where patients received normal saline at the rate 1.5 mg/kg IV followed by infusion at the same rate until the end of surgery The average serum lactate postoperative, before extubation, 6 hours and 24 hours of lignocaine group was 2.68±0.32 mmol/l, 1.26±0.22 mmol/l, 1.09±0.28 mmol/l, and 1.15±0.13 mmol/l, respectively (p&lt;0.001). Whereas the average serum lactates at postoperative, before extubation, 6 hours and 24 hours of normal saline group was 2.86±0.37 mmol/l, 2.64±0.65 mmol/l, 2.15±0.31 mmol/l, and 1.65±0.38 mmol/l, respectively (p&lt;0.001). Conclusion: Patients undergoing bowel surgery who received intraoperative IV lignocaine exhibited lower postoperative serum LDH and lactate levels compared to those who received normal saline. It was also concluded that indirectly intravenous lignocaine also improves postoperative outcomes by reducing pain and hospital stay.

Primary Protection of Diosmin Against Doxorubicin Cardiotoxicity via Inhibiting Oxido-Inflammatory Stress and Apoptosis in Rats.

Doxorubicin (DOX) is the cornerstone of chemotherapy. However, it has dose-dependent cardiotoxic events that limit its clinical use. This study was intended to investigate the efficiency of DOX as an anti-cancer against the MCF-7 cell line in the presence of diosmin (DIO) and to appraise the protective impact of DIO against DOX cardiotoxicity in vivo. In vitro study was carried out to establish the conservation of DOX cytotoxicity in the presence of DIO. In vivo study was conducted on 42 adult female Wistar rats that were equally allocated into 6 groups; control, DIO (100 mg/kg), DIO (200 mg/kg), DOX (20 mg/kg, single dose i.p.), DIO (100 mg/kg) + DOX, received DIO orally (100 mg/kg) for 30 days, then administrated with a single dose of DOX and DIO (200 mg/kg) + DOX, received DIO orally (200 mg/kg) for 30 days, then administrated with DOX. In vitro study showed preservation of cytotoxic activity of DOX on MCF-7 in the presence of DIO. In vivo study indicated that DOX altered electrocardiograph (ECG) parameters. Also, it yielded a significant rise in CK-MB, cTnT and LDH serum levels and cardiac contents of MDA, IL-1β; paralleled by a significant drop in cardiac IL-10 and SOD. Moreover, significant upregulation of Bax, TNF-α, and HIF-1α, in concomitant with significant downregulation of Bcl-2 mRNA in cardiac tissue have been recorded in the DOX group. Furthermore, histopathological description of cardiac tissues showed that DOX alters normal cardiac histoarchitecture. On the opposite side, DIO pretreatment could ameliorate ECG parameters, suppress IL-1β and enhanceIL-10, promote activity of SOD and repress MDA. Additionally, downregulation of Bax, TNF-α, HIF-1α and upregulation of Bcl-2 have been demonstrated in DIO-pretreated rats. Furthermore, the histopathological examination of cardiac tissues illustrated that DIO had a favorable impact on the protection of heart histoarchitecture. DIO is suggested for protection against acute cardiotoxicity caused by DOX without affecting antitumor activity.

Clinical and paraclinical approach to community-acquired pneumonia in obese individuals

Introduction. Obesity is a metabolic disease that presents a real challenge for the medical system due to the significant increase in the number of obese people in recent decades. Currently, 38% of the global population is overweight or obese. Obesity is an important risk factor for multiple chronic pathologies and lung infections, especially pneumonia. For obese subjects, chronic proinflammatory status due to an excess of fat cells is characteristic. Material and methods. This prospective cohort study is based on clinical and laboratory examinations of patients hospitalized with community-acquired pneumonia in the Department of Internal Medicine at Holy Trinity Municipal Hospital, Chisinau, Republic of Moldova. The study included 210 patients with community-acquired pneumonia, divided into two groups: the base group (group 1) consisted of 105 patients with varying degrees of obesity, and the control group (group 2) consisted of 105 normal-weight patients. The research was conducted according to the principles of the Helsinki Declaration - WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects. The study was approved by the Research Ethics Committee of the Nicolae Testemiţanu State University of Medicine and Pharmacy, with the issuance of favorable opinion no. 46 from March 27, 2018. All patients were examined clinically and paraclinically (radiological examination, pulse oximetry screening, complete blood count, erythrocyte sedimentation rate, fibrinogen, LDH, C-reactive protein, oxidative stress markers). The obtained data were statistically analyzed using Statistical Package for the Social Sciences (SPSS) version 20. Results. According to the obtained data, the most common comorbidities associated with obesity were cardiovascular and metabolic diseases. The main symptom that prevailed in the obese was dyspnea (97%). Obese subjects showed more frequent signs of acute respiratory failure (86.7%), required oxygen therapy with an average duration of 7.62±6.23 days, showed increased serum levels of LDH (286.31±94.66 U/L) and C-reactive protein (66.08±71.44 mg/l), data that influenced the clinical course of pneumonia. Conclusions. Patients with obesity and community-acquired pneumonia presented with infectious symptoms and acute respiratory failure, increased values of inflammatory markers, and required oxygen therapy more frequently compared to those of normal weight.

Role of inflammatory markers in predicting mortality and outcome of acute encephalitis syndrome in children of Eastern Uttar Pradesh India

Background: The present study was performed to study the role of inflammatory markers viz. C-reactive protein, procalcitonin, serum ferritin and serum lactate dehydrogenase in predicting the mortality and outcome in patients with acute encephalitis syndrome admitted to pediatrics ICU, BRD medical college, Gorakhpur. Methods: 140 patients/children of the age group ranging from 1 year to 16 years admitted in the acute encephalitis syndrome unit of BRDMC during 1 August 2021 to 31 July 2022 were analyzed with the prospective observational study. Results: Vaccination status (p&lt;0.001) and socioeconomic status (p=0.020) were associated with mortality outcome in AES patients. Serum procalcitonin levels with cut off value &gt;0.10 mg/dl and serum LDH levels with cut off value of 480u/L have shown a positive association with the mortality in AES patients. (p=0.041 and p=0.038, and strength of association is 0.67 and 0.65, respectively. C-reactive protein with a cut-off value 10 mg/dl and serum ferritin with a cut-off value 140 ng/ml have shown no association with mortality with p values of 0.143 and 0.267, respectively. The Area under the ROC curve is maximum for serum procalcitonin (0.937) with a cut-off value 0.10 ng/dl with 100% sensitivity and 75.8% specificity (confidence interval 95%: 0.894-0.980). The negative predictive value is 100% and PPV is 13.7%. Similarly, the area under the ROC curve for CRP with a cut-off 10mg/dl is 0.900 (confidence interval 95%: 0.841-0.959) with 100% sensitivity of and 64.8%. specificity. Consequently, the negative predictive value is 100 % and the positive predictive value of 11.1%. Conclusions: For predicting the mortality in AES patients 2 prognostic markers viz. C reactive protein and procalcitonin can prove to be promising prognostic screening tests, and therefore, both the tests are advised consecutively.

#1883 SUrvey of renal Biopsy database and Anti-cancer dRUg therapy in Japan (SUBARU-J study)

Abstract Background and Aims The frequency of consultations for renal complications associated with anti-cancer drug therapy has greatly increased in recent years, but the actual situations remain yet to be fully understood. We aimed to investigate the clinical outcomes of anti-cancer drug therapy-associated renal complications, using the Japan Renal Biopsy Registry (J-RBR), a nationwide registry system in Japan. Method This nationwide survey was performed in 449 cases with “drug-induced” checked in J-RBR database from 2018 to 2021. In total 449 subjects, top-ranked histopathological diagnoses were as follows, TIN (49.8%), TMA (14.5), MN (10.0), MCNS (6.5), FSGS (4.4), Vasculitis (2.2) and others (12.2). Regardless of the causative agent, TIN was the most common diagnosis. Though, it was followed by TMA or MN in anti-cancer drug (n = 139)- or non-anticancer drug (n = 190)-related cases, respectively. Because there was also TMA included as 2nd highest in causative-agent unidentified cases (n = 120), we employed total 259 subjects of anti-cancer drug-related and causative-agent unidentified for this survey. Our surveillance files investigating on renal pathology, medications and cancer prognosis were distributed. Of the 224 cases with a file uploaded, a total of 135 anti-cancer drug-related cases confirmed by the information were analyzed. Patients’ clinical data collected at pre- and post-biopsy as well as histopathological diagnoses were used for epidemiological and clinicopathological analyses. Mann-Whitney U test or chi-square test was used for continuous or categorical variables. Overall survival (OS) was estimated using Kaplan–Meier method and compared by log-rank test. Results In total 135 subjects, top-ranked histopathological diagnoses were as follows: tubulointerstitial nephritis (TIN; 64 cases), thrombotic microangiopathy (TMA; 48), focal segmental glomerulosclerosis (FSGS; 5), IgA nephropathy (IgAN; 4), acute tubular necrosis (ATN; 3), minimal change nephrotic syndrome (MCNS; 3), crescentic glomerulonephritis (CrGN; 2), membranoproliferative glomerulonephritis (MPGN; 2) and others (4). 80% of TIN and 75% of TMA, the most frequent diagnoses in our survey, were associated with immune-checkpoint inhibitors (ICI) and anti-angiogenic therapy (AAG), respectively. All IgAN, MCNS and CrGN cases were ICI-related. Proton pump inhibitors and antibiotics were used concomitantly in TIN (p = 0.054) and TMA (p &amp;lt; 0.001), respectively. Among cases with TIN, their OS in the subgroups of targeted therapy (Tx), and the combination with Tx and conventional cytotoxic agents (Combi) seemed to be worse than that of cytotoxic agents alone (CTx); it may be due to more cases in the Tx and Combi subgroups with treatment response category of progressive disease (by RECIST criteria). In contrast, among TMA cases, OS in each of the three subgroups of Tx, CTx, and Combi seemed to be overlapped, suggesting the prognostic impact of TMA on OS. The serum LDH level was higher in TMA associated with CTx (CTx-TMA) than that with others (Fig. 1: 393.2 vs. 225.1 U/L, p = 0.06). Of note, Kaplan-Meier curves for OS in TMA cases with increased LDH (&amp;gt;220 U/L) showed poor prognosis in CTx-TMA than in others-TMA (Fig. 2: p = 0.018). Conclusion Our nationwide survey using J-RBR registry database with renal biopsy data provides a snapshot of kidney complications associated with anti-cancer drug therapy. Higher LDH in CTx-TMA cases may be associated with systemic TMA, probably leading to the poor prognosis. To explore the detail of anti-cancer drug-associated TMA and other complications, further research employing more sample size is warranted in the future.