Administration Of Anti-inflammatory Drugs Research Articles

Chemotherapy: a double-edged sword in cancer treatment.

Chemotherapy is a well-known and effective treatment for different cancers; unfortunately, it has not been as efficient in the eradication of all cancer cells as been expected. The mechanism of this failure was not fully clarified, yet. Meanwhile, alterations in the physiologic conditions of the tumor microenvironment (TME) were suggested as one of the underlying possibilities. Chemotherapy drugs can activate multiple signaling pathways and augment the secretion of inflammatory mediators. Inflammation may show two opposite roles in the TME. On the one hand, inflammation, as an innate immune response, tries to suppress tumor growth but on the other hand, it might be not powerful enough to eradicate the cancer cells and even it can provide appropriate conditions for cancer promotion and relapse as well. Therefore, the administration of mild anti-inflammatory drugs during chemotherapy might result in more successful clinical results. Here, we will review and discuss this hypothesis. Most chemotherapy agents are triggers of inflammation in the tumor microenvironment through inducing the production of senescence-associated secretory phenotype (SASP) molecules. Some chemotherapy agents can induce systematic inflammation by provoking TLR4 signaling or triggering IL-1B secretion through the inflammasome pathway. NF-kB and MAPK are key signaling pathways of inflammation and could be activated by several chemotherapy drugs. Furthermore, inflammation can play a key role in cancer development, metastasis and exacerbation.

Effects of inflammatory prostatitis on the development and progression of benign prostatic hyperplasia: A literature review.

Benign prostatic hyperplasia is a major disease that affects the quality of life of middle-aged and older men. Although >70% of men aged >70years have pathological benign prostatic hyperplasia, its pathogenesis and progression remain unclear. In this article, we reviewed the scientific literature on this condition and examined the development of lower urinary tract symptoms. Clinically, the weight of the prostate is not always proportional to the severity of the symptoms, and many factors can influence the progression of benign prostatic hyperplasia. Other than androgens, chronic inflammation can play an essential role in its development and the induction of symptoms, especially in symptomatic hyperplasia, because inflammatory cell infiltration is frequently observed in the prostate. Inflammation-induced changes in the prostate environment lead to changes in gene expression and subsequent chronicity of inflammation. It has been suggested that chronic asymptomatic prostatitis might be associated with changes in prostate structure and subsequent symptoms. In animal studies, the administration of anti-inflammatory drugs in rats with chronic prostatitis prevented the infiltration of inflammatory cells and increased the gland-to-stroma ratio. It is hoped that future research on the molecular biology of asymptomatic prostatitis might help to develop new therapeutic strategies for lower urinary tract symptoms associated with symptomatic prostatitis. Our conclusions provide a comprehensive insight into the prevalence and development of benign prostate hyperplasia and the treatment methods that can be used to treat it.

Targeting TL1A/DR3 Signaling Offers a Therapeutic Advantage to Neutralizing IL13/IL4Rα in Muco-Secretory Fibrotic Disorders.

Mucus secretion is an important feature of asthma that highly correlates with morbidity. Current therapies, including administration of mucolytics and anti-inflammatory drugs, show limited effectiveness and durability, underscoring the need for novel effective and longer lasting therapeutic approaches. Here we show that mucus production in the lungs is regulated by the TNF superfamily member 15 (TL1A) acting through the mucus–inducing cytokine IL-13. TL1A induces IL13 expression by innate lymphoid cells leading to mucus production, in addition to promoting airway inflammation and fibrosis. Reciprocally, neutralization of IL13 signaling through its receptor (IL4Rα), completely reverses TL1A-induced mucus secretion, while maintaining airway inflammation and fibrosis. Importance of TL1A is further demonstrated using a preclinical asthma model induced by chronic house dust mite exposure where TL1A neutralization by genetic deletion or antagonistic blockade of its receptor DR3 protected against mucus production and fibrosis. Thus, TL1A presents a promising therapeutic target that out benefits IL13 in reversing mucus production, airway inflammation and fibrosis, cardinal features of severe asthma in humans.

Investigations on suckling piglets castrated under automated isoflurane anesthesia

Investigation of defensive reactions, piglet losses, post-bleeding and recovery time of suckling piglets castrated under automated isoflurane anesthesia as well as measurements of isoflurane concentrations in ambient air and estimation of the cleaning and disinfection success of anesthesia masks. A total of 955 suckling piglets (age: 4.0 ± 1.2 days; weight: 2.0 ± 0.5 kg) were castrated under automated isoflurane anesthesia (PorcAnest 3000®) after the administration of a non-steroidal anti-inflammatory drug. Reactions during the procedure were assessed before castration using the interdigital claw reflex and during castration by defensive movements and vocal response. The piglets' recovery time was evaluated in the stable corridor (pass 1) and the farrowing pen (passes 4-5). In 73 animals, the spermatic cord was cut with a scalpel and the post-operative bleeding visually evaluated. In addition, exposure measurements of isoflurane were performed and anesthetic masks were examined for total bacterial contamination and indicator bacteria before and after the anesthetic procedure and following their disinfection. Following insufflation of isoflurane for 90 seconds 94.3 % of the piglets and after prior testing of the interdigital claw reflex and possible extension of the anesthetic supply 95.3 % of the piglets showed no or minimal defensive movements during castration. An anesthetic incident occurred in 0.9 % of the piglets, but no animal died. The recovery time lasted 7.3 ± 4.7 minutes (pass 1) and 6.2 ± 3.3 minutes (passes 4-5). Cutting the spermatic cord with a scalpel led to a higher post-bleeding score (p < 0.001) compared to use of the emasculator. Isoflurane concentrations in ambient air ranged between 4.5 und 28.1 mg/m3. Masks disinfection reduced the total germ count by 99.8 %. Contaminations with Escherichia coli and MRSA were no longer detectable in 4 of 6 cases after disinfection. Isoflurane anesthesia led in over 94 % of the piglets to no or minimal defensive reactions during castration. Anesthetic incidents occurred rarely and no piglet losses were recorded. Therefore, automated isoflurane anesthesia is associated with a low risk for suckling piglets. Measurements of isoflurane concentrations on persons involved were below the internationally lowest limit value. Disinfection of the anesthesia masks may prevent germ transmission between animal groups via this potential vector.

Impact of Non-steroidal Anti-inflammatory Drug Administration for 12 Months on Renal Function.

Background: The use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of renal complications. Resolution of renal adverse effects after NSAID administration has been observed after short-term use. Thus, the present study aimed to investigate a series of patients with chronic musculoskeletal pain who underwent long-term NSAID administration followed by switching to tramadol hydrochloride/acetaminophen (TA) combination tablets to study the impact of NSAID-induced renal adverse effects.Methods: This was a longitudinal retrospective study of 99 patients with chronic musculoskeletal pain. The patients were administrated with NSAIDs daily during the first 12 months, followed by daily TA combination tablets for 12 months. Estimated glomerular filtration rate (eGFR) and serum levels of aspartate aminotransferase and alanine transaminase were measured at baseline, after NSAID administration and after TA administration.Results: eGFR was significantly reduced after 12-month NSAID administration (median, from 84.0 to 72.8 ml/min/1.73 m2), and the reduction was not shown after the subsequent 12-month TA administration (median, 71.5 ml/min/1.73 m2). Reduction in eGFR was less in patients who received celecoxib (median, −1.8 ml/min/1.73 m2) during the first 12 months. There was no significant difference in aspartate aminotransferase and alanine transaminase in each period.Conclusions: Thus, patients receiving NSAIDs for 12 months displayed both reversible and irreversible reduction of eGFR upon cessation of NSAIDs and switching to TA. Our data highlight the potential safety benefit of utilizing multimodal analgesic therapies to minimize the chronic administration of NSAIDs.

Daily administration of ketoprofen restores AIH‐induced phrenic long term facilitation with prolonged chronic intermittent hypoxia

Acute intermittent hypoxia (AIH) elicits a form of spinal, respiratory motor plasticity known as phrenic long-term facilitation (pLTF). Preconditioning with a single day of chronic intermittent hypoxia (8 hours, 2 min hypoxic episodes with 2 min intervals) abolishes AIH-induced pLTF through a mechanism that requires systemic inflammation and spinal p38 MAP kinase activation (Huxtable et al., 2015). pLTF is restored by high-dose, systemic administration of the non-steroidal anti-inflammatory drug, ketoprofen, or spinal p38 MAP kinase inhibition. Similarly, preconditioning with 7 days of CIH (8 hours per day, 2 min episodes, 2 min intervals) abolishes pLTF, but we observed that phospho-p38 within phrenic motor neurons is unchanged from control rats (Gonzalez-Rothi and colleagues, unpublished). Thus, mechanisms whereby 7 days of CIH undermines AIH-induced pLTF are unclear. Since CIH induces time-dependent spinal inflammatory gene expression profiles over time (Smith et al., 2013), we hypothesize that prolonged CIH (versus a single day) blunts LTF through an inflammation-dependent mechanism that is independent of p-38MAP kinase. Thus, in ongoing experiments, the impact of anti-inflammatory drugs on AIH-induced pLTF in rats preconditioned with prolonged CIH (7 days). pLTF was restored when ketoprofen was administered each day just prior to the IH7 exposure (70% increase, p=.0013 vs. vehicle), but not when a single dose of ketoprofen was delivered just prior to assessment of pLTF (19% increase, p=0.9975 vs. vehicle). Upcoming experiments will explore the role of p38 MAP kinase with prolonged CIH exposure. These experiments are the first to explore shifting mechanisms whereby prolonged CIH and associated inflammation undermine phrenic motor plasticity. Such experiments are essential since chronic intermittent hypoxia is a hallmark of sleep apnea, a condition highly prevalent in individuals living with neurological disorders (spinal cord injury, ALS, etc.). It is therefore important to identify and mitigate factors which may undermine the potential for therapeutic interventions (i.e., repetitive AIH) to harness endogenous plasticity and ultimately improve breathing.

A novel mouse model for checkpoint inhibitor-induced adverse events.

Immune checkpoint inhibitors have demonstrated significant efficacy in the treatment of a variety of cancers, however their therapeutic potential is limited by abstruse immune related adverse events. Currently, no robust animal model exists of checkpoint inhibitor-induced adverse events. Establishing such a model will improve our mechanistic understanding of this process, which in turn will inform design of improved therapies. We developed a mouse model to determine inflammatory toxicities in response to dual checkpoint blockade in the presence of syngeneic tumors. Mice from susceptible genetic backgrounds received intraperitoneal injections of anti-mouse PD-1 and CTLA-4 antibodies. The mice were monitored for weight loss and histologic evidence of inflammation. Blood was collected for basic metabolic panels and titers of anti-nuclear antibodies. In parallel, mice were also treated with prednisolone, which is commonly used to treat immune related adverse events among cancer patients. Among all the genetic backgrounds, B6/lpr mice treated with anti-CTLA-4 and anti-PD-1 antibodies developed more substantial hepatitis, pancreatitis, colitis, and pneumonitis characterized by organ infiltration of immune cells. Mice that developed tissue infiltration demonstrated high serum levels of glucose and high titers of anti-nuclear antibodies. Finally, while administration of prednisolone prevented the development of the inflammatory adverse events, it also abrogated the protective anti-tumor effect of the checkout inhibitors. Genetic background and treatment modalities jointly modified the inflammatory adverse events in tumor bearing mice, suggesting a complex mechanism for checkpoint inhibitor-related inflammation. Future studies will assess additional genetic susceptibility factors and will examine possible contributions from the administration of other anti-inflammatory drugs.

Cinnamon Aqueous Extract Attenuates Diclofenac Sodium and Oxytetracycline Mediated Hepato-Renal Toxicity and Modulates Oxidative Stress, Cell Apoptosis, and Inflammation in Male Albino Rats.

Among commonly consumed anti-inflammatory and antimicrobial drugs are diclofenac sodium (DFS) and oxytetracycline (OTC), especially in developing countries because they are highly effective and cheap. However, the concomitant administration of anti-inflammatory drugs with antibiotics may exaggerate massive toxic effects on many organs. Cinnamon (Cinnamomum zeylanicum, Cin) is considered one of the most broadly utilized plants with various antioxidant and anti-inflammatory actions. This study aimed to evaluate the possible protective effects of cinnamon aqueous extract (Cin) against DFS and OTC hepato-renal toxicity. Eight groups (8/group) of adult male albino rats were treated orally for 15 days with physiological saline (control), Cin aqueous extract (300 mg/kg b.w.), OTC (200 mg/kg b.w.), single dose of DFS at the 14th day (100 mg/kg b.w.), DFS + OTC, Cin + DFS, Cin + OTC, and Cin + DFS + OTC. The administration of DFS and/or OTC significantly increased (p < 0.05) the serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea, creatinine, and uric acid. Serum levels of pro-inflammatory cytokines, as well as hepatic and renal malondialdehyde and nitric oxide metabolites, were also raised following DFS and OTC administration. Meanwhile, the activities of reduced glutathione, superoxide dismutase, and catalase in liver and kidney were significantly suppressed in DFS, OTC, and DFS + OTC treated rats. Moreover, hepatic and renal tissue sections from these rats exhibited overexpression of caspase-3 and cyclooxygenase-II on immunohistochemical investigation. The administration of Cin aqueous extract ameliorated the aforementioned deteriorations caused by DFS, OTC, and their combination. Conclusively, Cin is a promising protective plant extract capable of attenuating the oxidative damage, apoptosis, and inflammation induced by DFS and OTC either alone or combined, on hepatic and renal tissues.

THE FIRST EXPERIENCE OF LYMPHOTROPIC ANTIBACTERIAL THERAPY FOR ACUTE PANCREATITIS

Acute pancreatitis remains one of the most common surgical diseases of the abdominal cavity. Its incidence has been constantly increasing in recent years. Mortality remains high with pancreatitis: 15–45%. To study capacity for increasing the effectiveness of treatment of acute pancreatitis by lymphotropic administration of antibacterial and anti-inflammatory drugs. We observed 17 patients with acute pancreatitis, with the average age of 47.7 years; all patients were hospitalized within the first two days of the disease. The treatment was performed in addition to the infusion therapy in accordance with the order of the Ministry of Health of Ukraine No. 297 dated April 2, 2010, using lymphotropic administration of antibacterial therapy, which was tested at the Department of Surgery of SSU and differed in that antibacterial and anti-inflammatory drugs were injected regionally into the pancreas. In the first 4 days, according to the ultrasound findings, the size of the inflamed pancreas decreased from 31.25, 18.5, and 27.25 cm to 25.25, 15.75, and 18 cm, and the size of the spleen decreased from 262.64 cm3 to 160.99 cm3, which is the evidence of drug targeted effect on the pancreas and spleen. Lymphotropic antibacterial and anti-inflammatory therapy used for 4 days reduced the size of the head, body and tail of the gland by 6.4, 3.9, and 7.0 cm. The reduction in the size of the gland contributed to the elimination of clinical signs of inflammation, especially pain, and leukocytes number decrease, which indicates the "targeted" effect of the drugs. The reduction in the size of the spleen from 308.9 cm3 to 227.1 cm3 proves the effect produced by lymphotropic use of drugs on the immune system. This is also supported by corrected immunoglobulin levels.

FDA-Approved Drugs with Potent In Vitro Antiviral Activity against Severe Acute Respiratory Syndrome Coronavirus 2.

(1) Background: Drug repositioning is an unconventional drug discovery approach to explore new therapeutic benefits of existing drugs. Currently, it emerges as a rapid avenue to alleviate the COVID-19 pandemic disease. (2) Methods: Herein, we tested the antiviral activity of anti-microbial and anti-inflammatory Food and Drug Administration (FDA)-approved drugs, commonly prescribed to relieve respiratory symptoms, against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the viral causative agent of the COVID-19 pandemic. (3) Results: Of these FDA-approved antimicrobial drugs, Azithromycin, Niclosamide, and Nitazoxanide showed a promising ability to hinder the replication of a SARS-CoV-2 isolate, with IC50 of 0.32, 0.16, and 1.29 µM, respectively. We provided evidence that several antihistamine and anti-inflammatory drugs could partially reduce SARS-CoV-2 replication in vitro. Furthermore, this study showed that Azithromycin can selectively impair SARS-CoV-2 replication, but not the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). A virtual screening study illustrated that Azithromycin, Niclosamide, and Nitazoxanide bind to the main protease of SARS-CoV-2 (Protein data bank (PDB) ID: 6lu7) in binding mode similar to the reported co-crystalized ligand. Also, Niclosamide displayed hydrogen bond (HB) interaction with the key peptide moiety GLN: 493A of the spike glycoprotein active site. (4) Conclusions: The results suggest that Piroxicam should be prescribed in combination with Azithromycin for COVID-19 patients.

Risk factors of post-tonsillectomy hemorrhage in adults.

ObjectiveTonsillectomy is an essential surgery and is conducted on both children and adults. However, the risk factors of post‐tonsillectomy hemorrhage for adult patients remain unclear. In this study, we analyzed post‐tonsillectomy hemorrhage in adult patients.MethodsWe retrospectively analyzed 325 adult patients who underwent a tonsillectomy between 2014 and 2018 in our facilities.ResultsThe average age of this study's population was 31.7 ± 10.5 years (range: 19‐70 years), and 250 (76.9%) patients were male. Overall, post‐tonsillectomy hemorrhage occurred in 71 (21.8%) patients and 5 (1.5%) patients required a second surgery for hemostasis. Post‐tonsillectomy hemorrhage often occurred on postoperative day zero or six. Using multiple logistic regression analysis, current smoking status (odds ratio 3.491; 95% confidence interval 1.813‐6.723), male sex (odds ratio 3.924; 95% confidence interval 1.548‐9.944), and perioperative non‐steroidal anti‐inflammatory drug administration (odds ratio 7.930; 95% confidence interval 1.004‐62.64) were revealed as overall post‐tonsillectomy hemorrhage risk factors. To analyze the hemorrhage period after tonsillectomy, we categorized the post‐tonsillectomy hemorrhage patients into the primary (bleeding within postoperative day one) and secondary hemorrhage (bleeding on or after postoperative day two) groups. The current smoking status and older age were risk factors for primary hemorrhage and the current smoking status and sex (male) were risk factors for secondary hemorrhage.ConclusionsIn this study, smoking status, sex, and perioperative non‐steroidal anti‐inflammatory drug administration were the clinical risk factors for adult post‐tonsillectomy hemorrhage. Thus, smoking cessation is, at least, mandatory for patients who receive tonsillectomy to avoid post‐tonsillectomy hemorrhage.Level of Evidence4

Perioperative Nonsteroidal Anti-inflammatory Drugs (NSAID) Administration and Acute Kidney Injury (AKI) in Major Gastrointestinal Surgery: A Prospective, Multicenter, Propensity Matched Cohort Study.

This study aimed to determine the relationship between early postoperative nonsteroidal anti-inflammatory drug (NSAID) administration and postoperative acute kidney injury (AKI) and anastomotic leak. NSAIDs have analgesic, opioid-sparing, and anti-inflammatory effects. However, their postoperative use is limited by concerns around increased risk of AKI and anastomotic leak. A secondary analysis of a multicenter, prospective cohort study including patients undergoing elective or emergency major gastrointestinal surgery from September to December 2015 across 173 hospitals in the United Kingdom and ireland. Exposure to early postoperative NSAIDs was defined as NSAID administration on postoperative days 0 to 3. The primary outcome was the 7-day postoperative AKI rate. Propensity score matching was used to balance treatment groups and estimate treatment effects that are presented as odds ratios, alongside the corresponding 95% confidence interval (CI). Overall 19.8% (1039/5240) of patients received early NSAIDs. AKI rates were 10.6% in the early NSAID group and 14.9% in the no NSAID group. The anastomotic leak rate in patients who received an anastomosis was 4.8% in the NSAIDs group and 6.0% in the no NSAIDs group. Following propensity score matching, early use of NSAIDs was not significantly associated with AKI (adjusted odds ratio 0.80, 95% CI 0.63-1.00, P = 0.057). This finding was consistent in subgroup analyses by NSAID dosage and timing. In patients who had a gastrointestinal anastomosis, NSAIDs were not associated with anastomotic leak (adjusted odds ratio 0.85, 95% CI 0.58-1.21, P = 0.382). Administration of NSAIDs in the early postoperative period is safe in selected patients following major gastrointestinal surgery.

Evaluation of renal and hepatic blood value screening before non-steroidal anti-inflammatory drug administration in dogs.

To evaluate the potential association between signalment, history and physical examination findings and elevated renal and hepatic blood values before non-steroidal anti-inflammatory drug administration in dogs. Secondary objectives were to investigate clinicopathologic differences between dogs that were and were not prescribed a non-steroidal anti-inflammatory drug. Medical records of 81 dogs that underwent renal and hepatic blood value screening before drug administration via a non-steroidal anti-inflammatory drug blood panel were reviewed retrospectively. Patient signalment, history and physical examination findings were recorded. Six (7%) dogs had an elevated blood urea nitrogen, 2 (2%) dogs had an elevated creatinine, 24 (30%) dogs had an elevated alanine aminotransferase, 29 (36%) had an elevated aspartate aminotransferase and 14 (17%) had an elevated alkaline phosphatase. Forty-five (56%) dogs had an elevation in at least 1 renal or hepatic blood value. Dogs less than 8 years of age and with a longer duration of clinical signs were less likely to have an elevated renal or hepatic blood value. Dogs with elevated hepatic blood values were less likely to be prescribed a non-steroidal anti-inflammatory drug; however, this was not true for elevated renal parameters alone. The results of this preliminary study suggest that blood value screening before non-steroidal anti-inflammatory drug administration may be important for dogs greater than 8 years of age. Hepatic enzyme elevations may play a greater role in clinical decision making in comparison to renal parameters.

Outcomes from Experimental Testing of Nonsteroidal Anti-Inflammatory Drug (NSAID) Administration during the Transition Period of Dairy Cows.

Simple SummaryThe treatment of dairy cows with nonsteroidal drugs is applied experimentally to investigate the relevance of inflammation during the periparturient period. Despite appearing healthy, dairy cows throughout the transition period and mainly after parturition can develop a pro-inflammatory status that may negatively influence milk production and cows’ health. The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) has been demonstrated to have both positive or negative effects on health and milk production, depending on the type of inhibition mechanism, the dose administered and the cows’ lactation numbers. At present, the safety and efficacy of NSAIDs have not been irrefutably demonstrated; therefore, their use to improve metabolic and inflammatory status, as well as milk production and cow health after parturition, should be carefully evaluated.During the transition period, dairy cows experience great physiological stress caused by changes in metabolism and in the immune and endocrine systems. A pro-inflammatory state is another difficulty faced by even apparently healthy animals. The most significant negative consequences of inflammation in dairy cows are substantial impairment of milk production and deleterious effects on cows’ health in extreme cases. Nonetheless, a certain degree of inflammation is necessary to sustain physiological adaptations. In recent years, many studies have attempted to determine whether the use of nonsteroidal anti-inflammatory drugs (NSAID) in the transition period of dairy cows could positively affect milk production and cows’ health by controlling the inflammation status. This literature indicates that NSAIDs that act as preferential inhibitors of cyclooxygenase-1 (COX-1) activity show important side effects (e.g., increased risk of retained placenta, culling, or metritis) even if milk production is, on average, ameliorated. In contrast, preferential inhibitors of cyclooxygenase-2 (COX-2) activity have overall positive effects on cows’ health, with potential beneficial effects on milk production. Furthermore, it is important to note that with certain NSAID treatments, milk discarding is mandatory to prevent contamination with drug residues, but increased milk production can compensate for the loss of milk revenue during the withdrawal period.

The Elevated Pre-Treatment C-Reactive Protein Predicts Poor Prognosis in Patients with Locally Advanced Rectal Cancer Treated with Neo-Adjuvant Radiochemotherapy.

The aim of the present study was to investigate the association of the pre-treatment C-reactive protein (CRP) plasma level with survival outcomes in a cohort of 423 consecutive patients with locally advanced rectal cancer treated with neo-adjuvant radiochemotherapy followed by surgical resection. To evaluate the prognostic value of the CRP level for clinical endpoints recurrence-free survival (RFS), local-regional control (LC), metastases-free survival (MFS), and overall survival (OS), uni- and multivariate Cox regression analyses were applied, and survival rates were calculated using Kaplan–Meier analysis. The median follow-up time was 73 months. In univariate analyses, the pre-treatment CRP level was a significant predictor of RFS (hazard ratio (HR) 1.015, 95% CI 1.006–1.023; p < 0.001), LC (HR 1.015, 95% CI 1.004–1.027; p = 0.009), MFS (HR 1.014, 95% CI 1.004–1.023; p = 0.004), and OS (HR 1.016, 95% CI 1.007–1.024; p < 0.001). Additionally, univariate analysis identified the MRI circumferential resection margin (mrCRM) and pre-treatment carcinoembryonic antigen (CEA) as significant predictor of RFS (HR 2.082, 95% CI 1.106–3.919; p = 0.023 and HR 1.005, 95% CI 1.002–1.008; p < 0.001). Univariate analysis also revealed a significant association of the mrCRM (HR 2.089, 95% CI 1.052–4.147; p = 0.035) and CEA (HR 1.006, 95% CI 1.003–1.008; p < 0.001) with MFS. Age and CEA were prognostic factors for OS (HR 1.039, 95% CI 1.013–1.066; p = 0.003 and HR 1.005, 95% CI 1.002–1.008; p < 0.001). In multivariate analysis that included parameters with a p-level < 0.20 in univariate analysis, the pre-treatment CRP remained a significant prognostic factor for RFS (HR 1.013, 95%CI 1.001–1.025; p = 0.036), LC (HR 1.014, 95% CI 1.001–1.027; p = 0.031), and MFS (HR 1.013, 95% CI 1.000–1.027; p = 0.046). The results support the hypothesis that an elevated pre-treatment CRP level is a predictor of poor outcome. If confirmed by additional studies, this easily measurable biomarker could contribute to the identification of patients who might be candidates for more aggressive local or systemic treatment approaches or the administration of anti-inflammatory drugs.

Histopathological aspects of co-administration of dexamethasone and diclofenac sodium on male albino rats

Background and objective: Treatment of an animal with dexamethasone will result in sinuses extension, fat accumulation in the liver, and enlargement of hepatocytes. Whereas, non-steroidal anti-inflammatory drugs (diclofenac sodium) administration may lead to degeneration and formation of wide areas in the form of sinusoidal. Hydropic degeneration possibly is seen in the tubular epithelial cells of the kidney tissue. This study aimed to assess the toxic and side effects of dexamethasone and diclofenac sodium on the liver and kidney in rats, whether used separately or together. Methods: A total of 40 male albino rats were divided into four groups of ten in each, including the control group. One set was treated with dexamethasone (1.6 mg/kg/day), the other was treated with diclofenac sodium (30 mg /kg/day), and the last was treated with both drugs together at the same dose without mixture. Both drugs were administered intramuscularly for 30 days. Sections from the liver and kidney were stained by Hematoxeline and Eosin, then examined under a microscope. Results: Histopathological variation in the liver and kidney tissue of the treated animals have revealed that each drug (dexamethasone, diclofenac sodium) showed a significant alteration. Strong changes (+ + +) were observed in kidney tissue include degeneration, inflammatory aggregation, fibrosis, and edema, whereas in liver showed central vein dilatation, necrosis, and kupffer cells hyperplasia. Treating with the two drugs together, less alteration (+) in the tissues was noticed. Conclusion: The effect of both used drugs (dexamethasone and diclofenac sodium) was observed on the liver and kidney tissues of the experimental animals (rats) regardless of being applied separately or the two together. A probable inhibition role of the two drugs on each other have been noticed that lead to call for more detail investigation on this matter in years to come.

Timpanismo abomasal em bezerra da raça Holandesa

This paper reports a case of abomasal bloat in a Holstein heifer, after an episode of the complete fracture of the left thoracic limb, which occurred on the farm. The animal, with 15 days of age, was donated to Veterinary Teaching Hospital (Hovet) of Faculty of Veterinary Medicine and Animal Science of University of Sao Paulo (FMVZ/USP) where it was operated, resulting in a complete fracture consolidation and no post-surgical complications. At 52 days of age, the heifer manifested acute apathy, anorexia, abdominal discomfort, and diarrhea. After physical and complementary (i.e., blood count and abdominal ultrasound) examinations and the assessment of nutritional management, the calf was diagnosed with abomasal bloat. Therefore, the following treatment was performed: correction of dehydration, antibiotic therapy, administration of a non-steroidal anti-inflammatory drug, and attempt of gas release through the esophageal tube. Moreover, dietary adjustments were made and consisted in interrupting the supply of concentrate, decreasing the volume of milk replacer, as well as supplying ruminal liquid, water, and green grass. Despite the acute and fatal characteristics seen in abomasal tympanism, the rapid identification of the initial clinical manifestations presented by the heifer allowed immediate therapeutic intervention, culminating in the survival of the animal and complete recovery at the end of the treatment.

Retrospective evaluation of acute kidney injury in dogs with pit viper envenomation (2008-2017): 56 cases.

To describe the clinicopathological characteristics of dogs that develop acute kidney injury (AKI) secondary to pit viper envenomation, and to describe the association between development of AKI and clinical course and outcome. Retrospective study. University teaching hospital. Client-owned dogs treated with at least 1 vial of antivenom following pit viper envenomation and that had at least 2 plasma creatinine concentrations measured during the course of hospitalization. None. Sixty-three dogs met the inclusion criteria. One was excluded due chronic kidney disease, and 6 were excluded due to nonsteroidal anti-inflammatory drug administration. Of the 56 dogs included in the study, 16 developed AKI (29%). Dogs with AKI received a significantly higher dose of antivenom, 8.7 ± 6.8 total vials versus dogs in the non-AKI group that received 4.2 ± 2.6 vials (P=0.006). Dogs in the AKI group were significantly more tachycardic (P=0.028), hypotensive (P=0.002), had a higher shock index (P=0.012), and were more likely to receive transfusions with packed red blood cells (P=0.042) than dogs in the non-AKI group. No significant association was identified between the development of AKI and length of hospitalization. The only factors that were significantly associated with degree of severity of AKI included the receipt of blood transfusion (P=0.006) and number of vials of antivenom administered (P=0.03). The development of AKI was significantly associated with outcome (P<0.001), with 5 of 16 (31%) dogs in the AKI group surviving to discharge, 7 of 16 (44%) dying, and 4 of 16 (25%) being euthanized versus 39 of 40 (98%) surviving to discharge in the non-AKI group and 1 of 40 (2%) dying in hospital. Development of AKI in dogs following pit viper envenomation carries an increased risk of mortality that is associated with severity of shock at presentation and increased doses of antivenom administration.

Osteogenic and Anti-Inflammatory Behavior of Injectable Calcium Phosphate Loaded with Therapeutic Drugs.

Bone fractures related to musculoskeletal disorders determine long-term disability in older people with a consequent significant economic burden. The recovery of pathologically impaired tissue architecture allows avoiding bone loss-derived consequences such as bone height reduction, deterioration of bone structure, inflamed bone pain, and high mortality for thighbone fractures. Actually, standard therapy for osteoporosis treatment is based on the systemic administration of biphosphonates and anti-inflammatory drugs, which entail several side effects including gastrointestinal (GI) diseases, fever, and articular pain. Hence, the demand of innovative therapeutic approaches for locally treating bone lesions has been increasing in the last few years. In this scenario, the development of injectable materials loaded with therapeutically active agents (i.e., anti-inflammatory drugs, antibiotics, and peptides mimicking growth factors) could be an effective tool to treat bone loss and inflammation related to musculoskeletal diseases, including osteoporosis and osteoarthritis. According to this challenge, here, we propose three different compositions of injectable calcium phosphates (CaP) as new carrier materials of therapeutic compounds such as bisphosphonates (i.e., alendronate), anti-inflammatory drugs (i.e., diclofenac sodium), and natural molecules (i.e., harpagoside) for the local bone disease treatment. Biological quantitative analyses were performed for screening osteoinductive and anti-inflammatory properties of injectable drug-loaded systems. Meanwhile, cell morphological features were analyzed through scanning electron microscopy and confocal investigations. The results exhibited that the three systems exerted an osteoinductive effect during later phases of osteogenesis. Simultaneously, all compositions showed an anti-inflammatory activity on inflammation in vitro models.

Therapeutic Manipulation of Macrophages Using Nanotechnological Approaches for the Treatment of Osteoarthritis.

Osteoarthritis (OA) is the most common joint pathology causing severe pain and disability. Macrophages play a central role in the pathogenesis of OA. In the joint microenvironment, macrophages with an M1-like pro-inflammatory phenotype induce chronic inflammation and joint destruction, and they have been correlated with the development and progression of the disease, while the M2-like anti-inflammatory macrophages support the recovery of the disease, promoting tissue repair and the resolution of inflammation. Nowadays, the treatment of OA in the clinic relies on systemic and/or intra-articular administration of anti-inflammatory and pain relief drugs, as well as surgical interventions for the severe cases (i.e., meniscectomy). The disadvantages of the pharmacological therapy are related to the chronic nature of the disease, requiring prolonged treatments, and to the particular location of the pathology in joint tissues, which are separated anatomical compartments with difficult access for the drugs. To overcome these challenges, nanotechnological approaches have been investigated to improve the delivery of drugs toward macrophages into the diseased joint. This strategy may offer advantages by reducing off-target toxicities and improving long-term therapeutic efficacy. In this review, we describe the nanomaterial-based approaches designed so far to directly or indirectly manipulate macrophages for the treatment of osteoarthritis.