24th Hr Research Articles

Location-specific prognostic significance of plaque burden, stenosis, and plaque morphology in coronary artery disease

Abstract Background The prognostic significance of coronary plaque localization, percentage atheroma volume (PAV), stenosis, and plaque morphology has been underexplored. Purpose To investigate the prognostic significance of plaque localization beyond plaque burden, presence of stenosis and plaque morphology. Methods Patients with no cardiac history who underwent coronary CTA were included. PAV, maximum diameter stenosis, and plaque morphology were assessed and classified into proximal, mid, or distal segments of the coronary tree. Major adverse cardiac events (MACE) were defined as death or non-fatal myocardial infarction. Results Among 2819 patients 267 events (9.5%) occurred during a median follow-up of 6.9 years. PAV of the proximal segments was strongly correlated to PAV localized at of the mid (R= 0.76) and distal segments (R = 0.74, p < 0.01 for both). When adjusted for traditional risk factors and presence of plaque on other locations, only proximal PAV was independently associated with MACE (3rd quartile HR 2.08, 95% 1.17–3.71, p=0.01 and 4th quartile HR 2.29, 95% CI 1.21–4.34, p=0.01). Similar results were seen for presence of stenosis. Proximal, mid, and distal PAV as a solitary metric (unadjusted) had similar predictive value for MACE with an AUC of 0.73 (95% CI 0.69-0.76) for proximal PAV and 0.72 (95% CI 0.68-0.76) for both mid and distal localized plaque). Similar results were obtained using diameter stenosis instead of PAV. The presence of low-attenuation plaque (LAP) in the proximal segments had additional prognostic value. Calcified or noncalcified PAV did not provide additional value beyond total location-specific PAV and presence of low-attenuation plaque. Conclusions Proximal located PAV is an independent predictor of death and non-fatal MI, while there was no incremental prognostic value of plaque localized at the mid or distal coronary segments. The presence of LAP in the proximal segments provided additional prognostic value for prediction of MACE.

Comparative Study Between Ultrasound Guided Serratus Anterior Plane Block versus Thoracic Erector Spinae Plane Block as Postoperative Pain Management in Modified Radical Mastectomy

Abstract Background Breast cancer is the most common malignancy in women, and its incidence continues to increase. Surgery is one of the mainstays of treatment of breast cancer, and Modified Radical Mastectomy (MRM) is one of the standard treatments for multi-centric disease or tumors with extensive coexistent ductal carcinoma in situ, where achieving a clear surgical margin becomes difficult with a segmental mastectomy. Objective This Study compared between Serratus Anterior Plane block and Thoracic Erector spinae block as efficacy of postoperative analgesia in Modified Radical Mastectomy. Patients and Methods This was a prospective controlled double blinded randomized clinical study that was conducted at Ain Shams University hospitals, Cairo, Egypt on Adult female patients undergoing modified radical mastectomy and were randomly assigned into two equal groups by computer generated method: Group A (control group): patients received general anaesthesia followed by Serratus Anterior plane block using only 20 ml 0.25% Bupivacaine (safety dose 3mg/kg). Group B(study group): patients received general anaesthesia followed by Thoracic Erector Spinae block using only 20ml bupivacaine 0.25 %. (safety dose 3mg /kg). Results In this study, we found that the postoperative VAS scores were better in Group SAP at 2nd, 4th, 6th and 12th hr as compared to group TES. The incidence of PONV and the requirement of Ondansetron were found to be similar in both groups. None of the patients in either group developed technique-related complications like hemodynamic instability, intravascular injection, pneumothorax, local anaesthetic systemic toxicity, and adverse effects like pruritus and respiratory depression. Conclusion USG-SAPB was effective and safe technique which provides better pain relief compared with the USG-TESP and reduced post operative opioid consumption. Therefore, the SAP can be used safely for post operative analgesia for patients undergoing MRM surgery to avoid the risk of developing chronic post mastectomy pain which reduces quality of life.

Utilization of diamondback puffer (Lagocephalus guentheri) biomass for the production of bioactive oligopeptides and their inflammation suppressing effects invitro

Development of new anti-inflammatory drugs has always been of prime interest due to various side effects exerted by common non-steroidal anti-inflammatory drugs (NSAIDs). Hence, due to the biochemical diversity and efficient anti-inflammatory activities of bioactive peptides from oceanic sources, their demand is increasing. In this study, the common diamondback puffer fish (Lagocephalus guentheri) muscle (PM) and visceral (PV) mass waste was used to produce enzymatic hydrolysates using trypsin, alcalase and papain digestion which were further used to obtain inflammation suppressing peptides. High pressure liquid chromatography (HPLC) analysis showed abundant essential amino acids like arginine, alanine, tyrosine, and glutamic acid in muscle as well as visceral part. The data obtained by the anti-inflammatory assays such as albumin denaturation inhibition and membrane stabilization assay of hydrolysates showed that alcalase 12th hr and 6th hr showed highest activity for PM and PV respectively. Further, out of the fractions obtained through ultrafiltration, 10-3 kDa showed higher anti-inflammatory activity which was subsequently purified with gel filtration chromatography. Moreover, the purified active peaks were analysed using LC-MS/MS to acquire a peptide sequence of MEPLGQG (731 Da) and LLHA (453 Da) for PMpep and PVpep respectively. In vitro studies revealed non-cytotoxic effects of peptide and pro-inflammatory cytokine suppression post LPS-stimulation in RAW264.7 cells. Thus, the puffer fish and other marine waste can be exploited for the isolation of potential nutraceutical and therapeutic compounds.

The Role of Graphene and BiodentineTM on Proliferation and Odontoblastic Differentiation of Pulp Stem Cells

Objective: The need for new biomaterials with biocompatibility, mechanical, and antimicrobial properties continues in regenerative endodontic clinical applications in dentistry. Biodentine™ is successfully used in vital pulp therapies and has regenerative effects. Additionally, graphene, which possesses good physicochemical, mechanical, and biological properties, promotes cellular biomineralization and osteogenic differentiation in dentistry, along with its neuroregenerative effect. This study aims to investigate the effects of graphene and Biodentine™ on cell proliferation, oxidative stress, and odontogenic differentiation in human dental pulp stem cells (hDPSCs). Methods: Cryopreserved hDPSCs purchased from American Type Culture Collection (ATCC) were used in our study (Cat No: PT-5025). hDPSCs were seeded into the E-plate wells and subsequently four different doses of graphene (12.5, 25, 50 and 100 µg/ml) and Biodentine™ (2, 4, 8 and 16 µg/ml) were added. Results of MTT, total antioxidant capacity (TAC), total oxidant status (TOS) and alkaline phosphatase (ALP) tests were obtained at the end of the 24th hr. 96 hr-real time cell index data were collected with xCELLigence® system. Resulting data were compared using one-way analysis of variance (ANOVA). Results: 12.5 µg/ml graphene and 2 µg/ml Biodentine™ were found to be the subgroups with the highest levels of cell proliferation and the lowest oxidative stress. Antioxidative effect was determined in all Biodentine™ doses but only in 12.5 µg/ml graphene. Odontogenic differentiation was observed in all doses of graphene and Biodentine™. Conclusion: 12.5 µg/ml graphene and 2 µg/ml Biodentine™ were observed to have positive impacts on the proliferation, oxidative stress and odontogenic differentiations of hDPSCs. Keywords: Cell proliferation. Graphene. Oxidative stress. Odontogenic differentiation. Tricalcium silicate

Influence of Allium Sativum on the Hypoglycaemic Activity of Gliclazide in Normal Rats: A Possible Approach to Herb-Drug Interaction

This study depicts the selected dose of Allium sativum (104 mg/kg body weight) on the hypoglycemic activity of preferred dose of gliclazide which are studied in normal wistar rats. Materials required for the study are procured from Sai Chemicals, Visakhapatnam, India. Mature wistar rats of both the sex were used for the study. Prior to the trial the rats were confined for 18 hr with access to water ad libitum. During the study water was removed. Orally gliclazide was administered at 0.5 mg/kg, 1 mg/kg, 2 mg/kg body weight to I, II and III groups respectively. Blood samples are taken by retro-orbital puncture at intervals of 0, 1, 2, 3, 4, 6, 8, 10, 12 & 16 hr and blood glucose levels were determined by GOD/POD method. The acute dose of Allium sativum when given along with gliclazide increased the hypoglycemic activity of gliclazide at 2nd, 6th and 8th hr intervals but it was significant at 2nd hr only and the effect was shown to be reduced at all other ie., 1st, 3rd, 10th and 12th hr time intervals. The aqueous extract of Allium sativum is influencing the absorption pattern of gliclazide since it was reported to have an increasing motility of the gastro intestinal tract.

Comparison of the effects of opioid-free anesthesia (OFA) and opioid-based anesthesia (OBA) on postoperative analgesia and intraoperative hemodynamics in patients undergoing spine surgery: A prospective randomized double-blind controlled trial.

Opioids form the basis of perioperative pain management but are associated with multiple side effects. In opioid-free anesthesia (OFA), several non-opioid drugs or neuraxial/regional blocks are used as substitutes for opioids. Ketamine, a N-methyl-d-aspartate antagonist, provides intense analgesia. However, there is a shortage of literature on the effects of ketamine-based OFA on hemodynamics (HD) and postoperative analgesia in patients undergoing thoracolumbar spine surgery. This prospective randomized controlled trial included 60 adult patients. The patients in Group OFA (n = 30) received OFA with ketamine and ketofol (1:5) infusion, and those in Group OBA (n = 30) received opioid-based anesthesia (OBA) with fentanyl and propofol infusion. The postoperative pain-free period, pain scores, rescue analgesia, intraoperative HDs, and postoperative complications were assessed. The mean pain-free period in Group OFA (9.86 ± 1.43 hr) was significantly higher than that in Group OBA (6.93 ± 1.93 hr) (P = 0.002). During the postoperative 48 hours, the total requirement of fentanyl was considerably lower in Group OFA (P < 0.05). There was a significantly higher incidence of hypertension in Group OFA (46%) and hypotension (43%) in Group OBA (43%), respectively. Postoperative nausea vomiting (PONV) was more common in Group OBA at the 2nd and 6th hr (P = 0.046 and P = 0.038). OFA with ketamine and ketofol provided adequate postoperative analgesia with a lower incidence of PONV after spine surgery. However, hypertension in the ketamine group and hypotension in the propofol group required fine titration of the infusion rate of drugs during the intraoperative period.

Prevalence and prognostic implications of myocardial injury across different waves of COVID-19.

The prognostic ability of myocardial injury across different waves of the COVID-19 pandemic is not well established. The purpose of this study was to evaluate the prevalence and prognostic implications of myocardial injury in the first and sixth wave of COVID-19. We conducted a retrospective observational study that included patients admitted to the emergency department with COVID-19 with data on concentrations of cardiac troponin during the first and sixth wave. We compared the prevalence of myocardial injury and its predictive capacity for 30-day all-cause death in both waves. A total of 346 patients were included (1st wave 199 and 6th wave 147 patients). The prevalence of myocardial injury was 21% with non-significant differences between waves. Myocardial injury was associated, in both waves, with a higher prevalence of comorbidities and with an increased risk of 30-day all-cause death [1st wave HR: 3.73 (1.84-7.55); p < 0.001 and 6th wave HR: 3.13 (1.23-7.92); p = 0.016], with non-significant differences in predictive capacity between groups after ROC curve analysis [AUC: 1st wave 0.829 (95% CI: 0.764-0.895) and 6th wave 0.794 (95% CI: 0.711-0.876)]. As limitations, this is a retrospective study with a relatively small simple size and troponin assay was performed at the discretion of the emergency physician so selection bias could be present. In conclusion, the prevalence of myocardial injury and its prognostic capacity was similar in both waves despite vaccination programs. Myocardial injury predicts short-term mortality in all COVID-19 patients, so they should be treated intensively.

Thyroid dysfunction after immune checkpoint inhibitors in a single-centre UK pan-cancer cohort: A retrospective study

PurposeThis study investigated thyroid dysfunction with immune checkpoint inhibitors (ICIs) in terms of proportions affected, risk factors, thyroid sequelae, and overall survival (OS). MethodsAmong patients with normal baseline free T4 (fT4) and thyroid stimulating hormone (TSH) receiving ICIs at a large cancer centre, proportions of hyperthyroidism/hypothyroidism were determined (any, subclinical [normal fT4, abnormal TSH], overt [abnormal fT4, abnormal TSH], isolated hyperthyroxinaemia/hypothyroxinaemia and secondary) with onset times and subsequent thyroid statuses. Associations of overt dysfunction with OS were estimated using Cox regression and methods robust to immortal time bias (time-dependent Cox regression and 3- and 6-month landmark analyses). Associations of baseline variables with overt hyperthyroidism and hypothyroidism were estimated using Fine and Gray regression. ResultsOf 1349 patients, 34.2% developed hyperthyroidism (10.3% overt), including 54.9% receiving combination ICIs, while 28.2% developed hypothyroidism (overt 9.3%, secondary 0.5%). A third of overt hypothyroidism cases occurred without preceding hyperthyroidism. Subclinical thyroid dysfunction returned directly to normal in up to half. Overt hyperthyroidism progressed to overt hypothyroidism in 55.4% (median 1.6 months). Melanoma treatment in the adjuvant vs. advanced setting caused more overt hyperthyroidism (12.1% vs. 7.5%) and overt hypothyroidism (14.5% vs. 9.7%). Baseline eGFR < 60 mL/min/1.73 m2 (HR=1.68, 1.07–2.63) was associated with overt hyperthyroidism and sex (HR=0.60, 0.42–0.87) and TSH (4th vs. 1st quartile HR=1.87, 1.10–3.19) with overt hypothyroidism. Overt dysfunction was associated with OS in the Cox analysis (HR=0.65, 0.50–0.85, median follow-up 22.2 months) but not in the time-dependent Cox (HR=0.79, 0.60–1.03) or landmark analyses (3-month HR=0.74, 0.51–1.07; 6-month HR=0.91, 0.66–1.24). ConclusionThyroid dysfunction affects up to half of patients receiving ICIs. The association with OS is unclear after considering immortal time bias. The clinical courses include recovery, thyrotoxicosis and de novo overt hypothyroidism. Adjuvant treatment for melanoma, where longer-term harms are of concern, causes more frequent/aggressive dysfunction.

Formulation and evaluation of controlled porosity oral osmotic pump tablets of furosemide

Oedema is an abnormal accumulation of fluid in the interstitium located beneath the skin and in the cavities of the body which can cause severe pain. Furosemide has been shown to be effective and safe in patients with hypertension and/ or coronary heart disease. Osmotic pump tablets deliver the drug in an optimized manner to maintain drug concentration within the therapeutic window and minimize toxic effects. The major objective of the study was to prepare and evaluate oral controlled porosity osmotic pump tablets of furosemide, to reduce the dosing frequency and thereby side effects, and to release the drug for a prolonged period in a controlled manner that is independent of pH and hydrodynamic activity. Pre-formulation studies and pre-compression parameters of tablet blends of osmotic pump tablets of furosemide were carried out. Oral-controlled porosity osmotic pump tablets of furosemide were prepared and subjected to different evaluation tests. Precompression parameters indicated that granules have a good flow property. All the formulations showed good mechanical strength. All the nine formulations showed a drug release of more than 60% in the 12th hour. Optimised formulation showed a drug release of 99.21% in 12th hr. Stability studies conducted indicate that the product is stable.

Preparation, statistical optimization, in-vitro evaluation and characterization of solid lipid nanoparticles of an anti-retroviral drug Nevirapine

Nevirapine-loaded solid lipid Nanoparticles (SLNs) were manufactured using lipid and emulsifying agent by hot homogenization method. The goal of research was to formulating a SLN system to target the HIV reservoir which is mostly found in the lymphatic system and to conquer the obstacle of drug itself. Also, nearly 50% of antiviral drugs fall within BCS class 2, which have low solubility. 44% antiviral drugs belongs to BCS class 3 have inadequate permeability and 6% belongs to class 4 with inadequate solubility and inadequate permeability. Depending on the NVP solubility and stable formulation, stearic acid as a lipid and poloxamer 188 and tween 80 as an emulsifying agent were chosen and SLNs were manufactured with the help of hot homogenization method. Optimization of independent variables such as lipid concentration, emulsifying agent concentration and no. homogenization cycle was carried. The effect of independent variables on the dependent variables i.e. particle size and entrapment efficiency was studied. Optimized formulation which was lyophilized (L-SLN) and this L-SLN additionally characterized using DSC, SEM and XRD analysis. Also, in-vitro drug release of optimized batch studied in 0.04 M Sodium phosphate buffer pH 6.8 containing 2% SLS, demonstrated 41.83% release at the end of 24th hr. Absence of low intensity in XRD indicated the presence of amorphous SLNs. SEM showed the morphology of SLNs. No prominent changes observed in the accelerated stability studies.

Effect of Intrathecal Morphine on Postdural Puncture Headache in Obstetric Anaesthesia.

Intrathecal morphine is used as an effective component of multimodal analgesia in postoperative analgesia in cesarean section patients. We aimed to analyze the relationship between intrathecal morphine administration and postdural puncture headache (PDPH), pain score and analgesia consumption in the postoperative period, and maternal fetal effects. One hundred four pregnant women aged ≥18 years (American Society of Anesthesiology physical status I or II, >36 weeks gestation) who were scheduled for elective cesarean section under spinal anaesthesia were included in this study. Spinal anesthesia consisted of bupivacaine with or without morphine (Group M: 10 mg heavy marcaine + 25 mcg fentanyl + 100 mcg morphine; Group F: 10 mg heavy marcaine + 25 mcg fentanyl). The effect of intrathecal morphine on PDPH, postoperative pain score, analgesia consumption, and maternal and fetal effects were recorded for 5 days. PDPH developed in a total of 33 patients (Group M: 18 and Group F: 15, P=0.274). When we evaluated PDPH with the VAS, there was no significant difference between the groups. The postoperative visual analogue scale (VAS) was lower in the morphine group, and no statistically significant difference was found in the VAS 1st hr and VAS 2nd hr, whereas the VAS 6th hr and VAS 24th hr were found to be statistically significant. There was no difference in terms of PDPH, the first analgesic requirement and postoperative nausea-vomiting, but meperidine consumption was lower in the morphine group. Low-dose intrathecal morphine did not affect the incidence of PDPH. It is an effective method that can be used in cesarean section patients without increasing the maternal and fetal side effects from postoperative analgesia.

Association of air pollution with postmenopausal breast cancer risk in UK Biobank

BackgroundWe investigated the association of several air pollution measures with postmenopausal breast cancer (BCa) risk.MethodsThis study included 155,235 postmenopausal women (of which 6146 with BCa) from UK Biobank. Cancer diagnoses were ascertained through the linkage to the UK National Health Service Central Registers. Annual exposure averages were available from 2005, 2006, 2007, and 2010 for NO2, from 2007 and 2010 for PM10, and from 2010 for PM2.5, NOX, PM2.5–10 and PM2.5 absorbance. Information on BCa risk factors was collected at baseline. Cox proportional hazards regression was used to evaluate the associations of year-specific and cumulative average exposures with BCa risk, overall and with 2-year exposure lag, while adjusting for BCa risk factors.ResultsPM10 in 2007 and cumulative average PM10 were positively associated with BCa risk (2007 PM10: Hazard ratio [HR] per 10 µg/m3 = 1.18, 95% CI 1.08, 1.29; cumulative average PM10: HR per 10 µg/m3 = 1.99, 95% CI 1.75, 2.27). Compared to women with low exposure, women with higher 2007 PM10 and cumulative average PM10 had greater BCa risk (4th vs. 1st quartile HR = 1.15, 95% CI 1.07, 1.24, p-trend = 0.001 and HR = 1.35, 95% CI 1.25, 1.44, p-trend < 0.0001, respectively). No significant associations were found for any other exposure measures. In the analysis with 2-year exposure lag, both 2007 PM 10 and cumulative average PM10 were positively associated with BCa risk (4th vs. 1st quartile HR = 1.19, 95% CI 1.10, 1.28 and HR = 1.29, 95% CI 1.19, 1.39, respectively).ConclusionOur findings suggest a positive association of 2007 PM10 and cumulative average PM10 with postmenopausal BCa risk.

POST OPERATIVE ANALGESIC EFFECT OF INTRATHECAL FENTANYL AS AN ADJUVANT TO 0.5% HYPERBARIC BUPIVACAINE COMPARED TO 0.5% HYPERBARIC BUPIVACAINE IN SUBARACHNOID BLOCK IN LOWER LIMB ORTHOPAEDIC SURGERIES: AN OBSERVATIONAL STUDY.

Background: Pain is an unkind sensory and sensitive practice associated with actual or potential tissue damage and also is associated with uncomfortable sensations in body. Postoperative pain management holds the key aspect of postoperative care. In this study, we have compared the intrathecal 0.5% hyperbaric bupivacaine with intrathecal fentanyl as adjuvant to 0.5% hyperbaric bupivacaine in terms of safety, efcacy, and postoperative analgesia in patients undergoing lower limb orthopaedic surgeries and also studied the side effects of the drugs used. An Material: analytical, prospective, observational study was conducted in Department of anaesthesia of a tertiary care teaching hospital. All adult patients eligible by the mentioned inclusion and exclusion criteria were considered as sample who were observed and analysed. Total 112 patients were included in the study, which were divided in two equal groups. Group I (BF)- Patients who received 3 ml of 0.5% hyperbaric bupivacaine and 25 μg of fentanyl intrathecally. Group II (B)- Patients who received 3 ml of 0.5% hyperbaric bupivacaine and 0.5 ml of CSF intrathecally. In Results: present study there was no statistical signicant difference in mean age, sex, weight, and ASA grade between two groups. In the study there was statistically signicant difference in mean VAS score between two groups at post op 3rd hrs,4th and 5th hrs. At these intervals mean VAS score was high in group II compared to group I. Mean time of First Rescue Analgesia in group I was 4.85 ± 0.47 hrs and in group II was 3.5 ± 0.53 hrs which highly statistically signicant. There was no statistical signicant difference in side effects amongst the two groups. There was statistically signicant difference in mean HR between two groups at post op 4th and 5th hr. Mean HR was high in group II compared to group I at these two intervals. In the study there was no statistically signicant difference in mean SBP, DBP and MAP between two groups from baseline to post op 6 hrs. Present study concluded that addition of 25 μg fentanyl to intrathecal bupivacai Conclusion: ne offers longer duration of postoperative analgesia. So, it has suggested that fentanyl is a better choice with regards to postoperative analgesia in lower limb orthopaedic surgeries.

Chemical profiling and evaluation of toxicological, antioxidant, anti-inflammatory, anti-nociceptive and tyrosinase inhibitory potential of Portulacaria afra using in-vitro, in-vivo and in-silico studies

Portulacaria afra Jacq (Portulacaceae) is a medicinal plant used traditionally in the treatment of pain and inflammation. This study aimed to evaluate the phytochemical composition, toxicity, antinociceptive, and enzyme inhibition potential of P. afra. The methanol extract (PAME) was prepared through maceration and fractionated with ethanol to ethanol fraction of P. afra (ETPA). Both PAME and ETPA were found to be rich in total phenolic (TPC) and total flavonoid contents (TFC). Similarly, PAME showed the highest antioxidant potential through ABTS 93.16 ± 0.05 mg TE /g of dry extract (D.E.) while ETPA showed maximum results (462 ± 1.44 mg TE/g) in the CUPRAC method. The RP-UHPLC-MS analysis of PAME showed tentative identification of 101 compounds in the positive mode and 14 compounds in the negative mode of ionization while GC–MS profiling gave a total of 15 compounds. The acute oral toxicity study of PAME revealed the safety and biocompatibility of the extract up to a dose of 5000 mg/kg orally in rats. In-vitro data revealed that varying concentrations of P. afra significantly (p < 0.05) inhibited heat-induced BSA denaturation compared to indomethacin in a concentration-dependent manner. PAME suppressed carrageenan-induced paw edema at the 4th hr with maximum inhibition. The analgesic efficacy of PAME was determined by the hotplate, writhing method, and tail-flicking rat models. In the hot plate method, PAME treated groups showed a significant effect (p < 0.0001). While in the writhing model, the PAME treated groups showed a significant (p < 0.0001) anti-nociceptive effect at 200 mg/kg and 400 mg/kg compared to the control group. Similarly, PAME treated groups in the tail flicking model showed a significant (p < 0.001) anti-nociceptive effect at 200 mg/kg and 400 mg/kg. A dose-dependent increase in latency time (8.78 ± 0.090 at (30 min), 11.39 ± 0.005 at (60 min), 12.14 ± 0.01 at (90 min) 15.19 ± 0.03 at (120 min), p < 0.0001 was observed, compared to the control group. Similarly, the extract and fraction showed significant inhibitory potential against tyrosinase in in vitro and in-silico studies. Conclusively the current study unveiled P. afra as a novel non-toxic source with good total antioxidant-mediated anti-inflammatory and analgesic potential.

COMPARATIVE STUDY OF THE USAGE OF RECTAL TRAMADOL SUPPOSITORY VERSUS WITHOUT SUPPOSITORY FOR POST-OPERATIVE PAIN MANAGEMENT IN CASES OPERATED UNDER SPINALANESTHESIA

Introduction: Various techniques and medications are employed to lessen postoperative discomfort. Present study aimed to assess the efcacy of pre-operative tramadol suppository administration for the management of post-operative pain in patients undergoing surgery under spinal anaesthesia, requirement of analgesia and duration of hospital stay. Material &amp; Method: The present comparative study with patients presenting to the department of General Surgery, AVMCH who were posted for elective surgeries &amp; with no evidence/signs of inammation/infection consenting were included in the study. Patients were grouped based on utility of tramadol suppository, cases were with administration of rectal suppository and control group was with no pre-operative administration of rectal suppository. The patients were assessed for the post-operative pain at different point of time, mean duration of hospital stay and any side effects like nausea, vomiting between the groups. Results: Total 152 patients included in the study, with mean age of 47.57yrs. The pain score was signicantly lower among the cases compared to control at 1st hr, 6th hr, 12th hr and 24th hr post-operative period. (p&lt;0.05) There was signicant shorter duration of hospital stay among the cases (2.3days) compared to controls (3.2days).(p&lt;0.05) Conclusion: A signicant pain management in post-operative period with the utility of tramadol suppository administration compared to the patients without suppository

Protective effects of melatonin receptor agonists on endotoxin-induced uveitis in rats.

Melatonin has an important role in regulating a variety of physiological functions of the body. We investigated the protective effects of Agomelatine (AGO) and Ramelteon (RAME) on Endotoxin-Induced Uveitis (EIU) in rats. 70 rats were randomly divided into fourteen groups. Healthy group normal saline, (IP), Uveitis group (200 μg/kg lipopolysaccharide (LPS), SC), DEX group (200 μg/kg LPS plus 1 mg/kg dexamethasone, IP), AGO20 group received 200 μg/kg LPS plus 20 mg/kg AGO, AGO40 group received 200 μg/kg LPS plus 40 mg/kg AGO, RAME2 group received 200 μg/kg LPS plus 2 mg/kg RAME, and group RAME4 received 200 μg/kg LPS plus 4 mg/kg RAME. Each group had two subgroups: the 3rd and 24th hr. The eye tissues were collected and investigated biomicroscopically (clinical manifestations and scoring, molecularly(qRT-PCR analyses of tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and caspase 3 and caspase 9 mRNA expression), biochemically (Superoxide dismutase activity (SOD), Glutathione (GSH), and malondialdehyde levels (MDA)) and histopathologically (staining with Harris Hematoxylin and Eosin Y). Melatonin receptor agonist treatment reduced the clinical score count of ocular inflammation in the uveitic rats. TNF-α, VEGF, caspase 9, and caspase 3 levels markedly decreased in the uveitic rats. Melatonin receptor agonists significantly ameliorated fixed changes in GSH, SOD, and MDA levels. Melatonin receptor agonists also ameliorated histopathological injury in eye tissues associated with uveitis. Melatonin receptor agonists ameliorated the inflammatory response in EIU. These findings suggest that melatonin receptor agonists may represent a potential novel therapeutic drug for uveitis treatment.

Morin provides therapeutic effect by attenuating oxidative stress, inflammation, endoplasmic reticulum stress, autophagy, apoptosis, and oxidative DNA damage in testicular toxicity caused by ifosfamide in rats.

In the present study, it was evaluated whether morin has a protective effect on testicular toxicity caused by ifosfamide (IFOS), which is used in the treatment of various malignancies. For this purpose, 100 or 200 mg/kg morin was given to Sprague Dawley rats for 2 days, and a single dose (500 mg/kg) IFOS was administered on the 2nd day. At the 24th hr of IFOS administration, animals were decapitated and testicular tissues were taken and the status of oxidative stress, inflammation, endoplasmic reticulum stress (ERS), autophagy, and apoptosis markers were analyzed by biochemical, molecular, and histopathological methods. According to the data obtained, it was determined that IFOS caused oxidative stress in testicular tissues. It was observed that inflammation, ERS, autophagy, apoptosis, and oxidative DNA damage occurred with oxidative stress. Morin treatment suppressed oxidative stress. Morin showed anti-inflammatory effects by reducing TNF-α and IL-1β protein levels. It also increased the mRNA transcript levels of the ERS marker ATF-6, PERK, IRE1, GRP-78, and CHOP genes, and the apoptosis marker genes Bax, Casp-3, and apaf-1. It up-regulated the anti-apoptotic protein Bcl-2 gene and the cell survival signal AKT-2 gene. Morin caused a decrease in beclin-1 protein levels and showed an anti-autophagic effect. In addition, morin attenuated oxidative DNA damage and decreased 8-OHdG immune-positive cell numbers. As a result, it was observed that IFOS caused cellular damage by activating various signaling pathways in testicular tissue, while morin exhibited protective properties against this damage.

Evaluation of protective effects of heat-inactivated cyprinid herpesvirus-2 (CyHV-2) vaccine against herpesviral hematopoietic necrosis disease (HVHND) in goldfish (Carassius auratus)

Cyprinid herpesvirus-2 (CyHV-2) is an important virus that causes herpesviral hematopoietic necrosis disease (HVHND) leading to huge economic losses in goldfish (Carassius auratus). However, until now no proper prophylactic measure or treatment is available for CyHV-2 infection in goldfish. Hence, in this experiment, we developed a heat-inactivated CyHV-2 vaccine and evaluated its performance in goldfish. Initially, CyHV-2 was propagated in the fantail goldfish fin (FtGF) cell line and the titer of the viral inoculum was 107.8 TCID50/ml. Subsequently, various temperatures (40 °C, 50 °C, 60 °C, 70 °C, and 80 °C) were evaluated to achieve the complete inactivation of CyHV-2. Only the viral inoculum inactivated at 80 °C for 1 h did not show any cytopathic effect in the FtGF cell line after five blind passages. Hence the heat-inactivated CyHV-2 vaccine developed at 80 °C was further used for immunization trials in goldfish. The experimental goldfish were intraperitoneally immunized with 300 μL of the heat-inactivated CyHV-2 vaccine. Subsequently, the kidney and spleen tissues were sampled at various time points post-vaccination (6th hr, 2nd day, 4th day, 6th day, 10th day, 16th day, and 30th day) to evaluate the expression of immune genes (IL-12, IL-10, IFN-γ, CD8, and CD4). A significant upregulation of immune genes was observed at various time points in the kidney and spleen tissue of the vaccinated goldfish. Furthermore, in order to study the efficacy of the vaccine, the experimental fish were challenged with CyHV-2 (107.8 TCID50/ml) after the 30th day post-vaccination. The survival of the fish in the vaccine group (86.7%) was significantly higher compared to the non-vaccinated group (20%). Moreover, the relative percentage survival of the vaccinated group was 83.34%. In spite of the single dose, the heat-killed vaccine developed in the present study elicited the immune response and offered better protection in goldfish against CyHV-2. However, further large-scale field performance evaluation studies are necessary to develop this vaccine on a commercial scale.

Evaluation of Sodium Alginate Stabilized Nanoparticles and Antibiotics against Drug Resistant Escherichia coli Isolated from Gut of Houbara Bustard Bird.

Alternative approaches and/or modified approaches to tackle resistance in gut microbes are need of the hour. The current study was planned to find the resistance modulation and toxicity potential of sodium alginate stabilized MgO nanoparticles and antibiotics against Escherichia coli (E. coli) isolated from the gut of Houbara bustard bird (n = 105 fecal samples). The preparations consisted of gel stabilized ampicillin (G+A), gel stabilized MgO and ampicillin (G+M+A), gel stabilized MgO and cefoxitin (G+M+C), gel stabilized tylosin (G+T), gel stabilized MgO and tylosin (G+M+T), and gel stabilized MgO (M+G). The fecal samples showed 53% (56/105) prevalence of E. coli which was found to be significantly (p < 0.05) associated with most of the assumed factors and resistant to multiple drugs. G+M+T showed the lowest (4.883 ± 0.00μg/mL) minimum inhibitory concentration (MIC) followed G+M+C, G+M+A, G+A, M+G, and G+T. Significant reduction (p < 0.05) in MIC with respect to incubation interval found at the 16th hr for G+M+A, G+A, and G+M+C that further remained nonsignificant (p > 0.05) onwards until the 24th hr of incubation. In the case of G+T and M+G, significant reduction in MIC was found at the 20th hr and 24th hr of incubation. Ecotoxicology and histopathology trials on snails showed mild changes in MICs of the preparations. The study thus concluded increasing drug resistance in E. coli of houbara bird while sodium alginate stabilized MgO nanoparticles and antibiotics were effective alternative antibacterial composites with mild toxicity.

The effect of epidural analgesia added to general anesthesia on systemic immune-inflammation index in radical prostatectomy surgery: A retrospective study.

Systemic immune-inflammation index (SII) is increasingly valued for its simplicity and predictability. Anesthesia/analgesia technique may affect cancer survey. The primary aim of this study is to offer a comparative evaluation for the effect of different anesthesia/analgesia techniques employed in radical prostatectomy surgery on SII, a new inflammatory index. Eighty-one patients who underwent radical prostatectomy between January 1, 2012, and December 31, 2020, were included in the study. We recorded oncological demographic data of Group G (n = 45) and Group GE (n = 36), preoperative and postoperative (within the first 4 hrs and 24th hr) SII values, perioperative surgical bleeding, and amount of blood transfusion. Despite the lack of significant difference in the SII values between the groups, both the peak SII level and the SII change in the postoperative period became higher in Group G than in Group GE. In addition, the amount of surgical bleeding and blood transfusion was observed to be significantly lower in Group GE (P < 0.001, P = 0.092, respectively). GE in radical prostatectomy surgery in terms of SII, the SII change in the postoperative period was more pronounced in Group G. However, a significant difference was noted in surgical bleeding in Group GE. We can conclude that comparing the SII values of different anesthesia techniques with prospective studies might thus create a difference in survival and metastasis at the micro-level.