Dose Of Diclofenac Research Articles

In vitro Antioxidant and In vivo Hepatocurative and Nephrocurative Activities of Aqueous Leaf Extract of Newbouldia laevis in Albino Rats

The in vitro antioxidant activity and in vivo hepatocurative and nephrocurative potential of Newbouldia laevis aqueous leaf extract (NLALE) was evaluated. The study used 30 male, albino rats (Rattus norvegicus) weighing 180 ± 20 g, of which 25 were intoxicated by oral administration of a single dose of diclofenac (100 mg/kg b. wt.). Animals were treated by oral administration of silymarin (200 mg/kg b. wt.), furosemide (1.5 mg/kg b. wt.) and NLALE (200 mg/kg and 400 mg/kg b. wt.) for seven consecutive days before animals were sacrificed on the 8th day and serum/plasma was analyzed for biochemical markers of hepatotoxicity and nephrotoxicity. Phytochemical screening of NLALE revealed the presence of alkaloids, flavonoids, glycosides, phenols, saponins, steroids and tannins. The extract scavenged DPPH radical, reduced Fe3+ and inhibited TBARs in comparable manner to ascorbic acid in vitro. NLALE also attenuated diclofenac-induced liver and kidney intoxication as indicated by the significantly (p<0.05) reduced levels of serum biomarkers of hepatotoxicity: ALT, AST, bilirubin, but increased total protein levels and nephrotoxicity: urea, creatinine, Na+ and K+. The observed effects are dose dependent as the 400 mg/kg b. wt. appeared to be more potent than the 200 mg/kg b. wt. dose. It may be concluded from this study that Newbouldia laevis leaf has ameliorative effect against diclofenac-induced hepatotoxicity and nephrotoxicity probably through antioxidative mechanism and the curative claim and the folkloric use of the plant in the treatment of liver and kidney diseases have been scientifically validated

Oral analgesia in fixed-time interval administration versus spinal morphine for post-Cesarean pain: a randomised controlled trial.

PurposeTo compare the efficacy of fixed-time-interval oral analgesia and spinal-morphine for management of post-Cesarean pain.MethodsIn this open-label, parallel-group, randomized, controlled trial, 200 women due to undergo elective Caesarean section with spinal anaesthesia were enrolled between July 2015 and April 2016. Patients were randomly assigned to receive either spinal fentanyl followed by oral doses of tramadol, paracetamol, and diclofenac at predetermined regular intervals of 6 h for the first 48 h, and rescue treatment with percocet (oxycodone and paracetamol; oral analgesia group), or spinal morphine and rescue treatment with oral tramadol, paracetamol, and diclofenac (spinal-morphine group). The primary outcomes were pain intensity during the postoperative 48 h, measured on a 10-point numeric rating scale (NRS) and expressed as area under the curve (AUC), and the number of breakthrough events of moderate to severe pain (defined as NRS score ≥ 4).ResultsThe oral analgesia group compared to the spinal-morphine group had similar mean pain intensity (AUC (120 ± 35 versus 121 ± 31, respectively; p = 0.8) but more events of moderate-to-severe breakthrough pain (4.8 ± 2 versus 3.8 ± 1.7, respectively; p = 0.0002). Higher rates and longer durations of pruritus, nausea, and vomiting were reported among patients receiving spinal morphine, as compared with oral analgesia. Satisfaction scores were high in both groups (8.2 ± 2.4 versus 8.7 ± 1.8 in the oral analgesia and spinal morphine, respectively; p = 0.23).ConclusionsBoth oral analgesia at fixed time intervals and spinal morphine are satisfactory methods for treating post-Caesarean pain.Trial registrationClinicalTrials.gov Identifier: NCT02440399, date of registration: 07/05/ 2015. URL: https://clinicaltrials.gov/ct2/show/NCT02440399?term=enav+yefet&rank=7.

A 25 mg rectal dose of diclofenac for prevention of post-ERCP pancreatitis in elderly patients

Objectives A 50–100 mg rectal dose of diclofenac or indomethacin is recommended for prophylaxis of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP); however, limited data are available regarding the appropriate dose to prevent PEP in elderly patients. We aimed to evaluate the efficacy and safety of 25 mg diclofenac in preventing PEP in elderly patients. Material and methods: Overall, 276 patients with naive papilla, aged over 75 years, were included in the present study between April 2013 and March 2020. We retrospectively evaluated the risk of PEP in patients over 75 years, administered with or without 25 mg diclofenac 30 min before ERCP using inverse probability of treatment weighting (IPTW) analysis. Results: Patients were categorized into the diclofenac group (83 patients) or non-diclofenac group (193 patients). The incidence rate of PEP in the diclofenac group was significantly lower than that in the non-diclofenac group (4% vs. 14%, p = .01). Multivariate analysis revealed that 25 mg diclofenac was an independent protective factor against PEP in elderly patients aged over 75 years (odds ratio [OR] = 0.17; 95% confidence interval [CI] = 0.04–0.67; p = 0.01). This protective effect of diclofenac against PEP remained robust after IPTW analysis (OR = 0.11; 95% CI = 0.03–0.40; p = .001). No adverse events related to diclofenac were observed. Conclusion: Diclofenac (25 mg) was considered effective and safe for preventing PEP in elderly patients. Our results may provide a new strategy for preventing PEP in elderly patients.

Evaluation of effect of Calotropis gigantea root bark in some animal models of Wister albino rats

Background: Calotropis gigantea is a well-documented traditional medicinal plant useful for many disease conditions. The present study deals with the effect of alcoholic extract of roots bark of Calotropis gigantean in some animal models.Methods: Acute anti-inflammatory activity of root extract was assessed on carrageenin induced paw edema and chronic antiinflammatory activity on cotton pellet granuloma formation in rats and compared with standard diclofenac sodium. Antiasthmatic activity was assessed in histamine and actylcholine induced bronchoconstriction in guinea pigs.Results: 100 and 200 mg/kg p.o. root extract of CG showed significant anti-inflammatory and bronchodilator activity. Antiinflammatory activity was higher than Diclofenac Sodium 50mg/kg. The combination of low dose diclofenac sodium 25mg/kg potentiated the effect. Inhibitory effect on synthesis and release of various inflammatory mediators might contribute to both of these actions. Steroid like phytoconstituents might be responsible for these effects. Further research is needed to understand the exact mechanism behind these effects.Conclusions: In the present study Calotropis gigantea root bark exhibited anti-inflammatory activity in animal models.

ID: 3519020 A 25 MG RECTAL DOSE OF DICLOFENAC FOR THE PREVENTION OF POST-ERCP PANCREATITIS IN ELDERLY PATIENTS

Population aging has increased the demand for ERCP in elderly patients. Elderly patients experience a lower rate of post ERCP pancreatitis (PEP) than non-elderly patients, but once it occurs in elderly patients, PEP can become more severe and even life-threatening. Many clinical studies have confirmed the efficacy of 50-100 mg rectal dose of diclofenac or indomethacin to prevent PEP, these studies are mainly focused on non-elderly patients and resulted in difficulty in choosing suitable prevention for PEP in elderly patients. Furthermore, the recommended dose may be toxic for elderly patients, especially frail patients with a low body weight or decreased renal function, who are more prone to adverse reactions.

Diclofenac Resensitizes Methicillin-Resistant Staphylococcus aureus to β-Lactams and Prevents Implant Infections.

Implant infections caused by methicillin‐resistant Staphylococcus aureus (MRSA) can cause major complications during the perioperative period. Diclofenac, one of the most widely used nonsteroidal anti‐inflammatory drugs, is often used to relieve pain and inflammation. In this study, it is found that high‐dose diclofenac can inhibit the growth of MRSA, and does not easily induce drug‐resistant mutations after continuous passage. However, low‐doses diclofenac can resensitize bacteria to β‐lactams, which help to circumvent drug resistance and improve the antibacterial efficacy of conventional antibiotics. Further, low‐dose diclofenac in combination with β‐lactams inhibit MRSA associated biofilm formation in implants. Transcriptomic and proteomic analyses indicate that diclofenac can reduce the expression of genes and proteins associated with β‐lactam resistance: mecA, mecR, and blaZ; peptidoglycan biosynthesis: murA, murC, femA, and femB; and biofilm formation: altE and fnbP. Murine implant infection models indicate that diclofenac combined with β‐lactams, can substantially alleviate MRSA infections in vivo. In addition, it is investigated that low dose diclofenac can inhibit MRSA antibiotic resistance via the mecA/blaZ pathway and related biofilms in implants. The synergistic effect of diclofenac and β‐lactams might have promising applications for preventing perioperative infection, considering its multitarget effects against MRSA.

Role of Vitamin B complex as an add-on therapy to diclofenac in patients with primary osteoarthritis of the knee

Objective: This study was conducted with the aim to evaluate the efficacy and safety of Vitamin B complex as an add-on therapy to diclofenac in patients with primary osteoarthritis (OA) of the knee. Materials and Methods: In this prospective, open-labeled, randomized, and comparative clinical study, a total of 130 patients of age >40 years with primary OA of knee attending orthopedics OPD were randomly allocated into two groups of 65 each, i.e., Group D and Group B. In Group D, patients received tablet diclofenac 75 mg and in Group B, patients received tablet Vitamin B complex along with diclofenac once daily for 4 weeks, respectively. Clinical assessment was done at baseline and at the end of 4 weeks and 8 weeks by the visual analog scale (VAS), WOMAC index, and Lequesne index. Results: During the intergroup comparison, it was found that Vitamin B complex as an add-on therapy to diclofenac produced statistically significant reduction in mean VAS pain score (P 0.05). Mild side effects were seen at 4 weeks, but no side effects persisted up to 8 weeks in both the groups. Conclusion: The present study suggested that Vitamin B complex as an add-on therapy was found to cause a significant reduction in pain score. It could be a promising drug in patients with OA to improve the analgesic effect, when combined can reduce the dose of diclofenac, thereby minimizing the side effects.

Połączenie diklofenaku z witaminami z grupy B – skuteczność i bezpieczeństwo w praktyce klinicznej

Diclofenac is one of the most commonly used non-steroidal anti-inflammatory drugs in the World, eagerly chosen for the therapy of skeletal, joint and muscle pain. However, the use of diclofenac is associated with side effects common for the entire class of drugs, including enhancement of cardiovascular risk. It has been shown that B vitamins are involved in many processes essential for the nervous system activity, as well as in the mechanism of initiating and transmitting pain stimuli. Besides, they have a synergistic analgesic effect when combined with diclofenac. Application of both drugs in analgesic therapy resulted in more effective pain relief, but also allowed for the reduction of diclofenac doses, leading to minimize the risk of side effects. The combination of B vitamins has a positive effect on the efficacy and safety of the therapy, which is important especially for low cardiovascular risk patients.

Rhabdomyolysis: an unusual complication following diclofenac and amitraz consumption

Amitraz is a pesticide with central alpha 2 agonistic action and diclofenac is a non- steroidal anti-inflammatory drug. Rhabdomyolysis is not commonly associated with either compound consumption. We report the case of a 28-year-old male who after presenting to us following 25ml of amitraz consumption, developed diffuse myalgia, muscle tenderness, cola coloured urine with oliguric acute renal failure which was followed by altered sensorium. Further probing revealed that he had also consumed 10 tablets of unknown dose of tablet diclofenac along with the amitraz. Rhabdomyolysis was suspected which was confirmed by an elevated creatinine phosphokinase. He was hydrated with IV fluids, given bicarbonate and N-acetylcysteine and in view of deteriorating renal function underwent 6 sessions of hemodialysis. Following the same, sensorium improved, urine output normalised, renal function improved and creatinine phosphokinase levels showed a decreasing trend indicating a reduction of the rhabdomyolysis. In poisoning cases it is often difficult to reliably confirm the drug consumed at the time of presentation. Therefore, like in our case, in addition to initial supportive measures, a periodic review of history, examination, regular monitoring of vitals and timely appropriate blood investigations can help confirm the nature of the poison and detect early the possible complications, and thus enable the early initiation of life saving treatment with improved patient outcomes.

Hepatotoxic effects of Diclofenac and Febuxostat combination on mice liver function tests after oral administration

Background: The liver is a major organ and involved in metabolizing various toxins, including chemicals, drugs, and natural substances.1 Diclofenac is a commonly used non-steroidal anti-inflammatory drug. Febuxostat is a novel non-purine xanthine oxidase inhibitor prescribed in various hyperuricemic states. Rise in liver enzymes with diclofenac use is a well-established fact. When both drugs are used in combination, these may lead to profound hepatotoxicity. To find out these facts this study was planned.
 Subjects and methods: An experimental study on mice was planned to explore these facts in University of Health sciences, Lahore. Animals were divided into 6 groups having 10 animals in each group. The animals were given drugs for 7 days. One served as control. 2nd group was given Diclofenac alone (100mg/kg), 3rd group was given Febuxostat (50mg/kg) alone while rest of three groups were administered drugs combination (Diclofenac + Febuxostat). Dose of Diclofenac (100mg/kg) kept constant while dose of Febuxostat increased in each group (5mg/kg, 10mg/kg and 50mg/kg). All drugs administered orally by gavage. After 7 days, the serum levels of liver enzymes assessed. Statistical analysis was performed using SPSS 20. One way ANOVA and Post hoc Tukey tests were applied. A p-value of ≤0.05 was considered statistically significant.
 Results: The results showed that Diclofenac and Febuxostat caused liver damage when used separately but hepatotoxicity was much significant (p-value <0.001) when drugs were used in combination.
 Conclusion: Both drugs Diclofenac and Febuxostat when administered in combination, causes more liver profound liver damage. That is why their use in combination should be avoided in clinical settings.

Initiation of febuxostat for acute gout flare does not prolong the current episode: a randomized clinical trial.

ObjectiveOur objective was to determine whether initiation of febuxostat during an acute gout flare prolongs the current episode.MethodsIn this randomized, placebo-controlled, single-blinded, multicentre trial, patients with acute gout flares within 72 h were randomized (1:1) to the placebo and febuxostat (40 mg/day) groups. All patients were administered diclofenac (150 mg/day) for 7 days and then open-labelled on the eighth day. Febuxostat 40 mg daily and diclofenac 75 mg daily were administered from day 8 through 28 for the remission period. The dose of diclofenac was 150 mg/day before remission in both arms, and the original protocol was maintained until remission. The primary outcome was ‘days to resolution’.ResultsWe randomized 140 patients, 70 into each arm. The mean days to resolution was 5.98 days [median 7.00, interquartile range (IQR) 2.45 days] for the placebo and 6.50 days (median 7.00, IQR 3.67 days) for the febuxostat group (P = 0.578). The rate of resolution within 7 days was 84.38% for the placebo group and 76.92% for the febuxostat group (P = 0.284). There were no statistically significant differences in joint pain, swelling, tenderness and erythema scores at days 1, 3, 5 and 7. The mean serum uric acid levels were 507.54 and 362.62 μmol/l for the placebo and febuxostat group, respectively, on day 7 (P = 0.000). The rate of recurrent gout flares was 10.00% for the placebo group and 6.56% for the febuxostat group from day 8 through 28 (P = 0.492).ConclusionInitiation of febuxostat administration during an acute gout flare did not prolong the duration of acute flares.Trial registrationChinese Clinical Trial Registry, http://www.chictr.org.cn/, ChiCTR1800015962

Evaluation of Single dose of Oral Diclofenac pre-operatively in patients undergoing laparoscopic cholecystectomy on pain management

Evaluation of Single dose of Oral Diclofenac pre-operatively in patients undergoing laparoscopic cholecystectomy on pain management

Diclofenac for prophylaxis of heterotopic ossification after hip arthroplasty: a systematic review.

Heterotopic ossification (HO) is defined as the formation of lamellar bone in extraskeletal soft tissues. HO can be a severe complication after hip arthroplasty but can possibly be prevented by postoperative treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or radiotherapy. Diclofenac is 1 of the most used drugs in HO prophylaxis because it is effective and long established. However, there is still no uniform therapy regimen in terms of duration, dose and side effect profile regarding the application of diclofenac in HO prevention. We have, therefore, conducted the first systematic review investigating diclofenac for HO prophylaxis after hip arthroplasty. The aim of this study is to assess the efficacy, dose and duration of diclofenac therapy in preventing HO after total hip arthroplasty (THA). According to the PRISMA Guidelines we performed a systematic literature search in EMBASE via Ovid, in MEDLINE via PubMed and in the Cochrane Library addressing all studies in English and German regarding the prophylaxis of HO with diclofenac after THA. We identified 731 potential studies and included 6 randomised controlled trials with 957 patients. The studies were heterogeneous with regard to duration of therapy, dose, comparative group and follow-up period. The therapy duration ranged from 9 to 42 days, the applied diclofenac doses ranged from 75 mg to 150 mg daily. Patients treated with diclofenac showed a significant reduction in the total incidence of HO regarding to the Brooker Classification compared to placebo and no clinically relevant ossifications occured (Brooker III and IV). Diclofenac is efficacious in the prevention of HO and can be used routinely after THA. The existing data indicates that a minimum dose of 75 mg diclofenac per day started on the first postoperative day for a minimum of 9 days is needed to prevent HO with an acceptable incidence of side effects, such as gastrointestinal symptoms.

Safety and efficacy of dexamethasone as an adjuvant to bupivacaine in bilateral transversus abdominis plane block in children undergoing major abdominal surgery

BackgroundThis prospective randomized controlled double-blind clinical study was conducted on 52 patients of both genders divided into two groups (26 patients each). Local anaesthetic solution of isobaric bupivacaine 0.25% (0.3 ml/kg) was prepared. Group A received bilateral transversus abdominis plane (TAP) block with bupivacaine and dexamethasone (0.3 mg/kg) while group B received bilateral TAP block with bupivacaine and volume of saline equal to the amount of dexamethasone given in group A. Patients were observed for FLACC pain scale at the time of discharge from the post-anaesthesia care unit and then every 2 h for 36 h after the operation. This study was conducted to assess the safety and efficacy of adding dexamethasone to bupivacaine on the quality of bilateral US-guided transversus abdominis plane (TAP) block in children undergoing major abdominal surgeryResultsDexamethasone added to local anaesthetic in ultrasound-guided TAP block significantly decreased FLACC score at 8, 10, and 12 up to 24 h postoperatively, The time to the first requested analgesia was prolonged in the dexamethasone group (P = 0.000). The total dose of acetaminophen consumption over 36 h after surgery was also reduced (P = 0.000), but no difference was found regarding the total dose of rectal diclofenac (P = 0.068).ConclusionAdding dexamethasone to isobaric bupivacaine TAP block reduces postoperative pain and analgesic requirements compared to isobaric bupivacaine TAP block alone in children undergoing major abdominal surgery.

Efficacy of low dose rectal diclofenac for preventing post-endoscopic retrograde cholangiopancreatography pancreatitis: Propensity score-matched analysis.

Acute pancreatitis is a major adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Rectal administration of non-steroidal anti-inflammatory drugs (NSAIDs) decreases the incidence of post-ERCP pancreatitis (PEP). However, the efficacy of low dose rectal NSAIDs for preventing PEP remains controversial. We performed a retrospective study of 301 patients with native papilla and a body weight of <50kg who underwent ERCP between September 2010 and October 2019. After July 2016, a 25mg dose of rectal diclofenac was routinely administered within 15min before ERCP (NSAIDs group, n=72) and the control group (n=229) consisted of patients undergoing ERCP before this date without treatment. We compared the incidence of PEP between the two groups using propensity score matching. A total of 66 pairs of patients in each group were selected. The patients and procedural-related factors were similar in both groups. In total, 15 patients (11.4%) developed PEP: 12.1% (8/66) in the NSAIDs group and 10.6% (7/66) in the control group (Odds ratio (OR) 1.2; 95% confidence interval (CI) 0.4-3.5; P=0.78). There was no significant difference in incidence of other adverse events related to ERCP between the two groups. Prophylactic administration of a 25mg dose of rectal diclofenac did not reduce the incidence of PEP in patients with a native papilla and a body weight of <50kg in this study and a certain dose of rectal NSAIDs, such as a 100-mg dose, should be administered regardless of body weight to prevent PEP.

Diclofenac Enhances Docosahexaenoic Acid-Induced Apoptosis in Vitro in Lung Cancer Cells.

Simple SummaryPolyunsaturated fatty acids (PUFAs) and non-steroidal anti-inflammatory drugs (NSAIDs) have limited anticancer capacities when used alone. We examined whether combining NSAIDs with docosahexaenoic (DHA) would increase their anticancer activity on lung cancer cell lines. Our results indicate that combining DHA and NSAIDs increased their anticancer activities by altering the expression of critical proteins in the RAS/MEK/ERK and PI3K/Akt pathways. The data suggest that DHA combined with low dose diclofenac provides more significant anticancer potential, which can be further developed for chemoprevention and adjunct therapy in lung cancer.Polyunsaturated fatty acids (PUFAs) and non-steroidal anti-inflammatory drugs (NSAIDs) show anticancer activities through diverse molecular mechanisms. However, the anticancer capacities of either PUFAs or NSAIDs alone is limited. We examined whether combining NSAIDs with docosahexaenoic (DHA), commonly derived from fish oils, would possibly synergize their anticancer activity. We determined the viability of lung cancer cell lines (NCI-H1573, A549, NCI-H1299, and NCI-H1975) after exposure to DHA and various NSAIDs. We further conducted cell apoptosis assays and analyzed apoptosis-associated proteins and some key proteins in the RAS/MEK/ERK and PI3K/Akt pathways using western blot analysis. We also determined the impact of the treatment on the expression of inducible cancer-related genes using nCounter PanCancer Pathways gene expression analysis. The results showed that the combination of DHA and NSAIDs increased suppression of cell viability in all the lung cancer cell lines tested compared to each of the compounds used alone, with diclofenac being the most potent NSAID tested. This synergistic effect is especially significant in A549 and NCI-H1573 cells. The combination treatment was more effective at inhibiting clonogenic cell growth and anchorage-independent growth in soft agar, inducing caspase-dependent apoptosis, and altering expression of critical proteins in the RAS/MEK/ERK and PI3K/Akt pathways. The data from this study demonstrate that DHA combined with low dose diclofenac provides greater anticancer potential, which can be further developed for chemoprevention and adjunct therapy in lung cancer.

Effescts of acute diclofenac exposure on intestinal histology, antioxidant defense, and microbiota in freshwater crayfish (Procambarus clarkii)

In the present study, we exposed Procambarus clarkii to different doses (0, 1, and 10 mg/L) of diclofenac (DCF). Meanwhile, we investigated the effects of exposure to DCF on intestinal histology, antioxidant defense, and microbial communities in P. clarkii. The results showed DCF caused histological changes in the intestines. Additionally, DCF induced significant changes in the expression of antioxidant genes including Mn-sod, cat, gst, and gpx. High-throughput sequencing of 16 S rRNA gene revealed DCF changed the diversity, richness, and composition of intestinal microbial communities. The relative abundances of the predominant phyla Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria showed significant changes at the phylum level after treatment with DCF. At the genus level, the most predominant genera with marked differences in abundance were Lucibacterium, Shewanella, Bacteroides, Anaerorhabdus, Aeromonas, Acinetobacter, Clostridium XlVb, Arcobacter, Bosea, and so on. To conclude, treatment with DCF could cause intestinal histological damage, induce significant changes of the expression of intestinal antioxidant genes, and impact the composition of intestinal microbiota in P. clarkii. This research will provide novel insights into the toxic effects of DCF on aquatic crustaceans.

Prenatal diclofenac exposure delays pubertal development and induces behavioral changes in rats

Diclofenac is a non-steroidal anti-inflammatory drug widely used by the general population and, although generally contraindicated during pregnancy, it is also used by some pregnant women. This study investigated endocrine, reproductive and behavioral effects of diclofenac in male and female offspring rats exposed in utero from gestational days 10–20. Pregnant rats were treated with diclofenac at doses of 0.2, 1 and 5 mg/kg/day via oral gavage. Anogenital distance (AGD), number of nipples, and developmental landmarks of puberty onset - vaginal opening (VO), first estrus (FE) and preputial separation (PPS) – were evaluated in the offspring. At adulthood, behavioral and reproductive parameters were assessed. Male and female rats were tested in the elevated plus maze test to assess locomotor activity and anxiety-like behaviors, while male rats were also evaluated in the partner preference test. No significant effects were observed on AGD and number of nipples in both males and females. Diclofenac treatment induced an overall delay in developmental landmarks of puberty onset in male and female offspring, which reached statistical significance for PPS at the lowest diclofenac dose. Prenatal exposure to all tested doses abolished the preference of male rats for an estrous female, suggesting an impairment of brain masculinization. No changes were observed on male or female reproductive parameters at adulthood. Overall, our results indicate that prenatal exposure to therapeutically relevant doses of diclofenac may have an impact in the pubertal development of rats and negatively affect male partner preference behavior.

Low Eosinophil Percentages as a New Predictive Marker for Infusion Reactions Due to Trastuzumab.

Infusion reactions (IRs) often occur with trastuzumab. Although premedication by non-steroidal anti-inflammatory drugs can be effective to a certain extent, IRs are still common and infrequently severe. Therefore, a predictive marker that can select patients requiring further prophylaxis is useful for appropriate prevention, but remains unclear. We conducted a retrospective analysis for 136 consecutive female inpatients aged 18 years and older who received 8 mg/kg of the initial trastuzumab administration for breast cancer with a 25-mg dose of rectal diclofenac before trastuzumab infusion between May 2007 and April 2019, in order to assess IRs. Overall, 57 patients were eligible for inclusion in the study. IRs were observed in 17.5% (10/57) of the patients. Univariate analysis showed that patients with a low eosinophil percentage (≤2%) were associated with IRs (p=0.016). A low eosinophil percentage can be a useful new predictive marker for trastuzumab-induced IRs in patients with breast cancer.

Efficacy of β-D-Mannuronic Acid [M2000] on the Pro-Apoptotic Process and Inflammatory-Related Molecules NFκB, IL-8 and Cd49d using Healthy Donor PBMC.

This investigation evaluates the pro-apoptotic and anti-inflammatory effects of β-D-mannuronic acid [M2000] compared to diclofenac, based on gene expression involved in apoptosis and inflammation process [including Bcl2, NFκB, IL-8 and Cd49d] in Peripheral Blood Mononuclear Cells [PBMCs] of healthy donors under exvivo conditions. The venous blood samples of twelve healthy volunteers with aged 25-60 years were collected in heparinized tubes. The healthy volunteers were selected from no smoking group and without using illicit drugs and suffering from diabetes. The PBMCs were separated and divided into untreated and treated groups. The PBMCs of each sample were cultured in 5 wells of culture plate, so that the first well consisted of 2×106 cells exposed by LPS-EB [1μg/ml] to stimulate PBMCs and absence of M2000 [untreated well]. The second, third, fourth and fifth wells containing 2×106 cells/well and LPS-EB, after 4 hours incubation at 37ºC, received 5, 25 and 50 μg/well of M2000 and 5 μg/well of diclofenac, respectively as treated group. The PBMCs were separated and RNAs were then extracted and cDNAs synthesized and gene expression levels were assessed by qRT-PCR. Furthermore, we studied whether M2000 is able to facilitate apoptosis in PBMCs. Our findings represent that the high dose of M2000 could significantly decrease the expression level of NFκB gene compared to untreated group (p < 0.0002). On the other hand, no significant change was observed in treated cells with diclofenac. All doses of M2000 could significantly augment apoptosis compared to untreated group [p < 0.0001]. Additionally, we observed the same apoptotic effects between the medium dose of M2000 and diclofenac. Besides, no significant reduction was shown in expression levels of IL8, Bcl2 and Cd49d genes in all doses of M2000 and diclofenac compared to untreated group. This experiment demonstrates M2000 as a new effective NSAID with immunosuppressive characteristics capable of stimulating apoptosis through lowering expression levels of NFκB gene, which might be probably considered as an appropriate drug for reducing the risk of developing inflammatory diseases and cancer.