Non-steroidal Anti-inflammatory Meloxicam Research Articles

Repurposing of non-steroidal anti-inflammatory drugs for combination therapies to combat multidrug-resistant S. aureus of bovine reproductive tract origin.

Multidrug-resistant bacteria have become the predominant etiology in bovine female reproductive tract infections and thus require effective treatment approaches. The main goal of this study was the molecular detection of mecA, blaZ, tetK, and aacA-aphD genes in Staphylococcus aureus (S. aureus) responsible for methicillin, beta-lactam, tetracycline, and aminoglycoside resistance respectively. Phylogenetic analysis was conducted to check the homology of staphylococcal genes with NCBI sequences. The in-vitro efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in combination therapies against MDR S. aureus was evaluated using well diffusion assay and checkerboard method. Vaginal swab samples (n = 384) collected from bovines suffering from endometritis, pyometra, and retained placenta were tested for S. aureus. Results showed a 17.96% overall prevalence. Both phenotypic and genotypic resistance was observed among S. aureus isolates with 50.72% and 37.68% isolates being confirmed as methicillin-resistant (MRSA), 36.23% and 18.84% isolates exhibiting beta-lactam, 40.58%, and 27.54% isolates showing tetracycline, and 33.33% and 36.23% isolates showing aminoglycosides resistance based on disc diffusion and gene confirmation, respectively. Phylogenetic analysis indicated homology with previously reported Pakistani isolates suggesting the possibility of MDR S. aureus transmission within and between animals. Synergy testing indicated that combinations of ceftriaxone-ketoprofen (153.77%), ceftriaxone-meloxicam (149.55%), amoxiclav-flunixin meglumine (106.06%), and oxytetracycline-flunixin meglumine (104.47%) showed synergy on well diffusion assay. Based on the fractional inhibitory concentration index by checkerboard method, oxytetracycline-meloxicam and gentamicin-ketoprofen combinations exhibited synergistic interaction. In conclusion, MDR S. aureus resistance was mitigated in-vitro through the combination of antibiotics (oxytetracycline, gentamicin) with NSAIDs (meloxicam, ketoprofen) that could be used to create therapeutic strategies for bovine reproductive issues.

Retrospective evaluation of the incidence of gastrointestinal bleeding in dogs receiving ophthalmic nonsteroidal anti-inflammatory drugs.

To report the incidence of gastrointestinal (GI) bleeding and associated risk factors in a population of dogs receiving ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs). Medical records of dogs prescribed ophthalmic NSAIDs (cases), dogs receiving systemic NSAIDs alone and dogs receiving systemic prednisone alone (controls). Data were collected retrospectively from the medical records of 204 dogs prescribed ophthalmic NSAIDs (diclofenac, ketorolac, or flurbiprofen), which were subdivided based on if they received any concurrent systemic NSAIDs or glucocorticoids, 136 dogs receiving a systemic NSAID (carprofen or meloxicam) alone, and 151 dogs receiving a systemic glucocorticoid (prednisone) alone at a referral hospital from 2015 to 2019. Gastrointestinal bleeds developed in 8/79 (10.1%) of topical NSAID-only cases, 10/136 (7.4%) of systemic NSAID controls, and 14/151 (9.3%) of systemic glucocorticoid controls, with no significant difference between the three groups (p = .6103). There were no significant differences in GI bleed rates between cases treated with ketorolac, diclofenac, or flurbiprofen (p = .160), although severe GI bleeding was only seen in ketorolac-treated dogs. Presence of a known concurrent risk factor for GI bleeding was significantly associated with the development of GI bleed in dogs on ophthalmic NSAIDs (p = .032). Dogs treated with ophthalmic NSAIDs developed GI bleeding at a frequency comparable to dogs receiving systemic NSAIDs or systemic glucocorticoids alone, suggesting that dogs receiving ophthalmic NSAIDs may be at increased risk of GI bleeding.

Methods of analgesia and euthanasia in backyard poultry

The keeping of chickens in the backyard is growing in popularity in urban and suburban areas, numbers of animals are increasing and as a result small animal practitioners are more and more frequently faced with chickens as patient. Clinical conditions in backyard poultry often require the treatment of pain. The challenges regarding the adequate use of analgesics include: 1. Recognition and assessment of pain, which necessitates good knowledge of chicken behaviour, 2. Selection of the adequate drug and dosage based on evidence that is often not available for chickens, but spread over different species of birds, and 3. Implementation of food safety regulations, which result from the dual use of backyard poultry as «food producing pets». Analgesics used in chickens include opiates, nonsteroidal anti-inflammatory drugs and local analgesics. The opiate butorphanol has been shown to have an analgesic effect of approximately two hours in chickens. Tramadol and methadone show some promise as analgesics, but more evidence is needed especially regarding bioavailability. The nonsteroidal anti-inflammatory drugs meloxicam and carprofen appear to have an analgesic effect. Variable metabolism between breeds of chickens and the risk of accumulation, especially when used for periods exceeding five consecutive days, need to be taken into account regarding dosage. Lidocaine and bupivacaine have successfully been used in chickens for nerve blocks and spinal anaesthesia and should be included as part of multimodal analgesia especially during surgery. In cases, where termination of life is necessary the preferred method consists of an injectable anaesthesia followed by intravenous application of a barbiturate.

Comparative analysis of neurological recovery and adverse effects in chondrodystrophic dogs with thoracolumbar intervertebral disc herniation treated with methylprednisolone versus non-steroidal anti-inflammatory drugs

Thoracolumbar intervertebral disc herniation is a common neurological disease presented to the small-animal practitioner. The use of methylprednisolone sodium succinate (MPSS) as an adjunct to surgical decompression in cases of acute spinal cord injury following intervertebral disc extrusion is controversial. A prospective study was undertaken to compare the perioperative use of MPSS and non-steroidal anti-inflammatory drugs (NSAIDs) in 40 chondrodystrophic dogs presenting with similar signs and undergoing spinal decompressive surgery. Twenty dogs received MPSS and 20 had NSAIDs administered preoperatively. Dogs were administered with either MPSS intravenously 20 min before surgery (30 mg/kg) or NSAID (meloxicam 0.2 mg/kg or carprofen 4 mg/kg) subcutaneously 20 min before surgery. Dogs were evaluated by neurological examination of gait 24 h postoperatively, at time of discharge, and then at 8 weeks. The neurological recovery was similar in both groups, but the frequency of side effects such as vomiting (MPSS group: 90% vs NSAIDs group: 55%), and anorexia within the first three days (present in all 20 dogs pretreated with MPSS) was significantly different, with complications being more prevalent in the MPSS group. This study showed that side effects were significantly more evident with the MPSS treatment group than with the NSAID group, with a neurological recovery similar in both groups.

The impact of clamp castration on the behaviour and body temperature of reindeer (Rangifer tarandus tarandus) – Effects of local anesthesia and non-steroidal anti-inflammatory drug.

Yearly, 2500–4000 reindeer (Rangifer tarandus tarandus) bulls are castrated in Finland, mostly without pain alleviation. No previous research exists concerning pain-related behaviours during castration in reindeer. Our aims were to investigate the effects of Burdizzo clamp castration on reindeer behaviour and rectal temperature during the procedure, and how these are affected by handling, local anaesthesia (LA) with lidocaine, and a non-steroidal anti-inflammatory (NSAID) drug meloxicam. A total of 44 1.5-year-old-reindeer were clamp castrated with either no pain alleviation (TRAD), perioperative meloxicam (NSAID), local lidocaine anaesthesia (LA), or with a combination of LA and NSAID (LA+NSAID), n = 11 in each treatment group. The fifth group was a non-castrated control (CONTROL), n = 11. We scored the reindeer behaviours, i.e., head, neck, and leg movements, nostril closure, panting, defecation, abdominal muscle contractions, and respiratory rate, from video recordings prior to and during castration and LA injection. We measured rectal temperatures (T) during the experiment and scored the number of reindeer reaching a T of at least 39.5ºC. Differences between treatments were analysed with the Kruskal-Wallis and chi square tests and differences between sampling intervals with the Wilcoxon signed rank and Friedman tests. During castration, nostril closures and abdominal muscle contractions occurred more often and for longer duration in the TRAD, NSAID, LA, and LA+NSAID groups than in the CONTROL group (p < 0.05 for all) or prior to castration (p < 0.001 for all). T increased during the experiment for all treatments. Overall, a total of 25 animals reached T 39.5ºC and treatments differed (p < 0.05): a larger number reached T 39.5ºC in the LA+NSAID group (11/11) than in the TRAD (2/10), NSAID (3/11), LA (4/11), or CONTROL (5/11) groups. The median respiratory rates decreased overall during the experiment for all treatments. During castration, TRAD had the highest median respiratory rate, differing from LA (38(40) vs. 32(20) breaths per min, n = 10 and 11, respectively, p = 0.003). Reindeer appear to express pain during clamp castration by closing their nostrils and contracting their abdominal muscles. Local lidocaine anaesthesia failed to significantly reduce the pain-related behaviours, at least with the 5-minute effect time used in this study. Moreover, a long handling time increased the rectal temperature of reindeer, especially when combined with other stressors such as injecting NSAIDs.

Effect of a single meloxicam administration on newborn Holstein-Friesian dystocia calves: Field results from the first 10 days of life.

Background and Aim:Calves have increased morbidity and mortality rates after dystocia. One cause is pain during birth, which reduces their colostrum intake. The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) may break this causality. This study aimed to determine the consequences of a single administration of the NSAID meloxicam to dystocia calves after birth.Materials and Methods:Fifty Holstein–Friesian calves born with dystocia from four dairy cattle farms were included in this study. The animals were randomized into two groups. The animals in Group I (n=25, treatment group) received subcutaneous 0.5 mg meloxicam/kg body weight 2-8 h after birth. The animals in Group II (n=25, control group) received a control substance (Amynin®, bovine infusion solution, Merial) with the same volume. The newborn calves were clinically examined on the 1st and 10th days of life. The information regarding the days in between was gathered by questioning the farmer.Results:There was a significant difference (p=0.04) only in calves with thin, mushy fecal consistency on the 10th day in the treatment group compared with the control group. Moreover, meloxicam had no effect on dystocia calves.Conclusion:Since NSAID administration did not produce a significant clinical effect, its necessity is questionable. Further studies should examine how modifying its application time would have an effect. The primary indicators of well-being, such as pain indicators in the blood, were not measured; however, these should be considered in subsequent studies.

Administration of meloxicam to improve the welfare of mice in research: a systematic review (2000 - 2020).

Although laboratory animals experience pain as a necessary component of the objectives of experimental protocols, the level of pain should be minimized through use of an adequate analgesic regimen. The non-steroidal anti-inflammatory drug meloxicam may be beneficial in alleviating post-operative pain in mice, although no regimen has been demonstrated as universally efficacious owing to differences in experimental protocols, strain, sex, and incomplete descriptions of methodology in the literature. The aim of this systematic literature review was to identify potential applications of meloxicam for pain management in experimental mice and to evaluate the general quality of study design. Searches of MEDLINE, Scopus and CAB Direct databases elicited 94 articles published between January 2000 and April 2020 that focused on the analgesic efficacy of meloxicam in the management of momentary or persistent pain in mice. The extracted data showed that most articles were deficient in descriptions of housing, husbandry, group size calculation and humane endpoint criteria, while few described adverse effects of the drug. A wide range of dosages of meloxicam was identified with analgesic efficiencies that varied considerably according to the different models or procedures studied. It was impossible to correlate the extracted data into a single meta-analysis because of the differences in experimental protocols and strains employed, the low representation of female mice in the studies, and incomplete descriptions of the methodology applied. We conclude that meloxicam has potential application for pain management in mice but that the dosage must be adjusted carefully according to the experimental procedures. Moreover, authors must take more care in designing their studies and in describing the methodology employed.

Toxic Effects of High-dose Meloxicam and Carprofen on Female CD1 Mice.

The nonsteroidal anti-inflammatory drugs meloxicam and carprofen are commonly used as analgesics in mice. The current recommended doses of meloxicam at 0.2-1.0 mg/kg once daily and carprofen at 5-10 mg/kg twice daily may not be adequate to provide analgesia in mice. Several studies have suggested that doses up to 20 mg/kg of meloxicam and carprofen are needed to provide analgesic efficacy. This study investigated the clinical safety of these higher doses of meloxicam and carprofen by evaluating their potential for renal and gastrointestinal toxicity. Female CD-1 mice were given 20 mg/kg of either meloxicam, carprofen, or an equivalent volume of saline subcutaneously once daily for 3 or 7 d. On day 4, mice treated for 3 d were euthanized, and on days 8 and 15, mice treated for 7 d were euthanized. Blood was collected by cardiocentesis for serum chemistry analysis. Feces was collected from the colon for fecal occult blood testing, and tissues were collected for histopathology. No clinically significant changes in serum chemistry profiles were found in the drug-treated mice at any time point as compared with the saline controls. Fecal occult blood and histologic evidence of gastritis was associated with meloxicam administration in mice evaluated at days 4 and 8. By day 15, there was no association with meloxicam treatment and the presence of fecal occult blood or gastritis. There was no association between fecal occult blood and gastritis in the carprofen or saline-treated mice regardless of the treatment durations. These findings suggest that 20 mg/kg of meloxicam in mice causes gastric toxicity when given for 3 or 7 d and should be used cautiously; however, carprofen at 20 mg/kg appears to have minimal toxic effects with regard to the parameters measured.

Meloxicam clinical effects

Pain syndromes, acute and chronic, against the background of inflammatory diseases (such as osteoarthritis (OA)), degenerative-dystrophic changes (involutive process, trauma) or systemic diseases (rheumatoid arthritis, etc.) dictate a steady increase in the intake of nonsteroidal anti-inflammatory drugs (NSAIDs). The choice of the most «safe NSAID» is based on the assessment of the toxicity index (the ratio when blocking cyclooxygenase (COX)) and the development of relative risks (the benefit/risk ratio). As well as those adverse events that can be detected with individual sensitivity to a specific NSAIDs, taking into account the anamnesis of previous diseases and intolerance to NSAIDs, existing chronic diseases (gastrointestinal tract, cardiovascular system, type 2 diabetes mellitus), limiting the appointment of NSAIDs. Considering these circumstances, the NSAID meloxicam (Amelotex) can be recommended for the treatment of various genesis pain syndromes. A number of studies have demonstrated the efficacy and safety of meloxicam with different methods of its administration (per oral (p/o), intramuscularly (i/m)) in the treatment of pain syndrome in the lower back, with OA, etc. Recent studies concern intravenous (i/v) meloxicam (30 mg) administration with moderate and severe postoperative pain syndrome. Today, the most commonly pain therapy scheme using meloxicam includes step-by-step administration of injectable and oral forms: meloxicam i/m (1.5 ml) for 3-5 days, followed by a transition to p/o (7.5-15 mg) intake for 14 days, or complex therapy with meloxicam (Amelotex), with muscle relaxant and B vitamins.

Effect of bupivacaine liposome suspension administered as a cornual nerve block on indicators of pain and distress during and after cautery dehorning in dairy calves

Dehorning is performed on a high percentage of dairies worldwide. Concern about the negative effect of dehorning on animal welfare has contributed to the development of new guidelines that require the use of pain management at the time of disbudding in the United States. However, livestock producers are limited in how to address this requirement due to a lack of (1) approved analgesic drugs, (2) analgesic options that control pain for an extended duration, and (3) analgesic formulations that are practical for producers to administer. The objective of this study was to evaluate the effectiveness of bupivacaine liposome suspension, a novel, long-acting, local anesthetic formulation administered as a nerve block at dehorning, compared with current industry standard analgesic approaches using lidocaine nerve blocks alone or in combination with the nonsteroidal anti-inflammatory drug meloxicam. Fifty male Holstein calves, 10 to 14 wk of age, were enrolled and randomly assigned to 1 of 5 treatment groups before cautery dehorning as follows: (1) bupivacaine liposome suspension block, oral placebo (BUP); (2) lidocaine block, oral placebo (LID); (3) lidocaine block, oral meloxicam (1 mg/kg of body weight; LID + MEL); (4) saline block, oral placebo (CON); and (5) saline block, oral placebo, sham dehorn (SHAM). Biomarkers were collected from 0 to 120 h postdehorning and included infrared thermography, mechanical nociceptive threshold (MNT), pressure mat gait analysis, chute defense and behavior scoring, and blood sampling for serum cortisol and prostaglandin E2 metabolites. Responses were analyzed using repeated measures with calf nested in treatment designated as a random effect, and treatment, time, and their interaction designated as fixed effects. At 2 h postdehorning, the BUP group had a higher MNT compared with the CON group. Furthermore, at 24 h postdehorning, the BUP group had a higher MNT compared with the LID group. Gait distance differed significantly between treatment groups; the CON, LID, and LID + MEL groups had an increased gait distance relative to the SHAM group. The CON group exhibited a higher chute defense behavior score during the dehorning procedure compared with all other treatments. Furthermore, the CON group exhibited more ear flicks than the BUP and LID + MEL groups postdehorning. At 4 h and 24 h after dehorning, the LID + MEL group had a lower average prostaglandin E2 metabolites concentration compared with all other treatment groups. These data showed that administration of bupivacaine liposome suspension as a cornual nerve block at the time of dehorning was as effective at controlling pain as a multimodal approach of lidocaine and meloxicam.

Intravenous ibuprofen for acute treatment of migraine: A double-blind, randomized, placebo-controlled pilot study.

To evaluate the efficacy and safety of intravenous (IV) Ibuprofen for acute treatment of migraine. IV nonsteroidal anti-inflammatory drugs (NSAIDs) are an alternative to oral NSAIDs, especially in patients with severe migraine who have emesis or gastroparesis. To date, only three IV NSAIDs (ketorolac, ibuprofen, and meloxicam) are available in the United States for use in moderate and severe pain, but no placebo-controlled trial is available for migraine. We performed a single-center, double-blind, randomized, placebo-controlled pilot study to evaluate the efficacy and safety of IV ibuprofen as an acute treatment of migraine (NCT01230411). Individuals with episodic migraine were screened at the Jefferson Headache Center. Qualified subjects were treated for migraine attacks within 2-72h following the headache onset with either 800mg of IV ibuprofen or placebo in 250ml saline bolus. Migraine pain intensity (4-point Likert scale) and associated symptoms were assessed at predetermined time points (0.25, 0.5, 1, 1.5, 2, 4, 8, 24h). The primary endpoint was pain relief at 2h after infusion. Important secondary endpoints included pain freedom at 2h, sustained relief over 24h, use of rescue therapy, and absence of associated symptoms. Adverse events (AEs) were also collected. Seventy-four participants were enrolled between 2011 and 2017. Forty-four subjects (female 33/44; 75.0%) with mean (SD) age 41.0 (11.2) 11.2 years came for the treatment. All treated subjects (n=44) were included in the analysis. Among them, 23 were randomized to receive IV ibuprofen. Both groups were demographically similar except for longer migraine duration (i.e., years lived with disease) in the active treatment than in the placebo group. At 2h posttreatment, pain relief was found in 74% (17/23) and 48% (10/21) after IV ibuprofen and placebo, respectively (odds ratio [OR] 3.12, 95% CI: 0.88-11.0; p=0.078). Other secondary endpoints at 2 and 24h were not significant. The longitudinal repeated-measures analysis within 2h on ibuprofen treatment showed significant pain relief (OR 2.47, 95% CI 1.08-5.7; p=0.033) and absence of associated symptoms: photophobia (OR 4.0, 95% CI 1.57-10.3; p=0.004), phonophobia (OR 3.12, 95% CI 1.16-8.4; p=0.025), and osmophobia (OR 3.45, 95% CI 1.01-11.8; p=0.048). AEs were observed in seven subjects in both groups, with arm pain being the most common. No serious AE was reported. This study did not meet the primary endpoint but showed pain relief and elimination of several associated symptoms within 2h on repeated-measures analysis. Although limited by small sample size and high placebo response, our results indicate that IV ibuprofen may be a safe and effective option for acute treatment of migraine, but more extensive studies are necessary.

Structural and functional state of Heren carcinoma after local fractional X-irradiation and irradiation combined with meloxicam

Background. One of the most important problems of oncology is the overcoming of therapeutic resistance of tumors, which occurs in particular due to increased levels of the enzyme cyclooxygenase 2 (COX-2). It is known that the growth of COX-2 and the product of its activity, prostaglandin-E2 in cancer, promotes such processes in the body as tumor growth, stimulation of proliferation, induction of cancer stem cells, inhibition of apoptosis, activation of angiogenesis, invasion, metastasis and development of chemoresistance. The use of COX-2 inhibitors, which are nonsteroidal anti-inflammatory drugs (NSAIDs), significantly limits these processes and improves survival and mortality in cancer patients, and in combination with chemotherapeutics eliminates the resistance they cause. Purpose – study of the structural and functional state of Guerin’s carcinoma cells after the combined use of nonsteroidal anti-inflammatory drug meloxicam and local X-irradiation in total doses of 1.0 and 10 Gy. Materials and methods. On 33 rats with inoculated Guerin’s carcinoma, the ultrastructure of tumor cells (TC) was studied using standard methods of electron microscopy 24 hours after the combined use of the meloxicam drug at a dose of 0.2 mg per 1 kg of body weight one day before the first and 2 hours before the second session fractional local X-irradiation in total doses of 1 and 10 Gy (twice daily at 0.5 and 5.0 Gy, respectively. The mitotic index (the number of cells in the state of mitosis per 100 TC,%), the apoptosis index (the number of cells in the state of apoptotic death per 100 TC,%) and the frequency of TC with small nuclei (%). Results. It was found that irradiation of Guerin’s tumor in a total dose of 10 Gy causes disturbances in the ultrastructure associated with damage to the nuclear apparatus of the TC. Pleiomorphism of the nuclei, the appearance of binucleated cells and micronuclei, a significant decrease in mitotic activity and a slight increase in the apoptosis index are observed. Stimulation of the functional activity of macrophages is also noted. Under irradiation in a total dose of 1 Gy, such effects are less pronounced or completely absent, such as, for example, the processes of phagocytosis. The frequency index of TC with small nuclei is equally reliably increased at both radiation doses. The administration of the drug meloxicam leads to a significant decrease in mitotic activity and an increase in the frequency of small cells, while the ultrastructural picture of the tumor remains almost unchanged. With the combined action of the drug and radiation in both doses, violations of the fine structure of the OC are identical to those found during irradiation. At the same time, the mitotic index in the group with the combined effect of the drug and radiation at a dose of 10 Gy is significantly lower than with only irradiation.In addition, at both doses, the frequency of small forms of PC significantly increases in comparison with the indicators of both the intact control group and the corresponding irradiation groups. Only in combination with radiation does meloxicam reliably stimulate apoptosis, while in other groups its index remains at the level of control values. The relationship was confirmed, which was constantly revealed in all experimental groups, between a decrease in the level of the mitotic index and an increase in the frequency of TC with small nuclei in Guerin’s carcinoma. An inverse correlation was found between these indicators (r = 0.80, P = 0.05). Conclusions. The combined action of the drug and irradiation significantly increases the effectiveness of both therapeutic factors due to the property of meloxicam to reliably inhibit proliferative activity and promote post-radiation development of apoptosis in tumor tissue. The presence of a correlation between the mitotic index and the frequency of cells with small nuclei in Guerin’s tumor may indicate the relationship between cell growth and division. Under the combined action of both investigated factors, changes in the tumor ultrastructure are mainly caused by irradiation. The administration of meloxicam increases the efficiency of the combined use of both therapeutic agents due to its ability to reliably inhibit proliferative activity and promote post-radiation development of apoptosis in tumor tissue. The presence of a correlation dependence between the mitotic index and the frequency of cells with small nuclei in Guerin’s tumor may indicate the relationship between the processes of cell growth and division.

Meloxicam with Filgrastim may Reduce Oxidative Stress in Hematopoietic Progenitor Cells during Mobilization of Autologous Peripheral Blood Stem Cells in Patients with Multiple Myeloma.

Autologous stem cell transplantation (ASCT) is a potentially curative therapy but requires collection of sufficient blood stem cells (PBSC). Up to 40 % of patients with multiple myeloma (MM) fail to collect an optimum number of PBSC using filgrastim only and often require costly plerixafor rescue. The nonsteroidal anti-inflammatory drug meloxicam mobilizes PBSC in mice, nonhuman primates and normal volunteers, and has the potential to attenuate mobilization-induced oxidative stress on stem cells. In a single-center study, we evaluated whether a meloxicam regimen prior to filgrastim increases collection and/or homeostasis of CD34+ cells in MM patients undergoing ASCT. Mobilization was not significantly different with meloxicam in this study; a median of 2.4 × 106 CD34+ cells/kg were collected in the first apheresis and 9.2 × 106 CD34+ cells/kg were collected overall for patients mobilized with meloxicam-filgrastim, versus 4.1 × 106 in first apheresis and 7.2 × 106/kg overall for patients mobilized with filgrastim alone. CXCR4 expression was reducedon CD34+ cells and a higher CD4+/CD8+ T-cell ratio was observedafter mobilization with meloxicam-filgrastim. All patients treated with meloxicam-filgrastim underwent ASCT, with neutrophil and platelet engraftment similar to filgrastim alone. RNA sequencing of purified CD34+ cells from 22 MM patients mobilized with meloxicam-filgrastim and 10 patients mobilized with filgrastim only identified > 4,800 differentially expressed genes (FDR < 0.05). Enrichment analysis indicated significant attenuation of oxidative phosphorylation and translational activity, possibly mediated by SIRT1, suggesting meloxicam may counteract oxidative stress during PBSC collection. Our results indicate that meloxicam was a safe, low-cost supplement to filgrastim mobilization, which appeared to mitigate HSPC oxidative stress, and may represent a simple means to lessen stem cell exhaustion and enhance graft quality.

Incidence of Heterotopic Ossification with NSAID Prophylaxis Is Low After Open and Arthroscopic Hip Preservation Surgery

PurposeWe evaluate the incidence of heterotopic ossification (HO) development with nonsteroidal anti-inflammatory drug (NSAID) prophylaxis in patients after open and arthroscopic hip preservation surgery.MethodsA retrospective review identified patients who underwent hip preservation surgery at a single institution within the past 3 years. Patients who underwent hip arthroscopy with or without periacetabular osteotomy (PAO) or femoral osteotomy (FO) were included. Those who did not receive 3-month postoperative radiographs were excluded. The incidence and Brooker classification (BC) of HO in patients taking Naproxen or another NSAID (meloxicam, celecoxib, indomethacin, or aspirin alone) was assessed using AP radiographs available from 3-, 6-, and 12-month follow-up appointments. Univariate analysis was conducted to compare numerical means and categorical data (significance level P = .05).ResultsA total of 328 hips (284 patients) were included. All patients received hip arthroscopy, while 71 patients (21.6%) received concurrent periacetabular osteotomy (PAO; n = 65) or femoral osteotomy (FO; n = 6). Overall, 276 hips (84.4%) received Naproxen for HO prophylaxis. In total, 5 of 328 hips (1.5%) developed HO (4, BC I; 1, BC III). The rate of HO development was significantly higher in males versus females (4 of 121 (3.31%) vs 1 of 207 (.48%), P = .0441). All 5 patients received arthroscopic cam resection and labral repair, and 1 patient also received PAO. Three patients in the Naproxen group (.91%) developed HO, which was not statistically different from those taking a different NSAID (.61%, P = .1797).ConclusionThe incidence of HO development was low with NSAID prophylaxis after hip preservation surgery.

ZMIANY MORFOLOGICZNE W TKANKACH STAWU KOLANOWEGO KRÓLIKA SPOWODOWANE CHOROBĄ ZWYRODNIENIOWĄ STAWÓW PO ZASTOSOWANIU EKSPERYMENTALNEJ METODY WYKORZYSTUJĄCEJ MEZENCHYMALNE KOMÓRKI MACIERZYSTE

The purpose of the study was to investigate the regenerative processes in the knee joint of rabbits with experimental osteoarthritis after using of allogeneic bone marrow stem cells and a traditional treatment with the non-steroidal anti-inflammatory drug Meloxicam. For the experiment were used 27 male California rabbits (males). Three groups of animals were formed: a control group; the first experimental group treated by the traditional method; the second experimental group treated with allogeneic mesenchymal stem cells (MSC). Animals in the three groups were subjected to osteoarthritis of the knee joint by double injection of 3.44% retinol acetate into the joint cavity at a dose of 1 ml at intervals of 7 days. Tissue from the affected site was sampled for histological examination at 7, 14 and 28 days. The histological sections were stained with haematoxylin-eosin and examined under a microscope. It has been established that intra-articular administration of 3.5 × 106 cells of allogeneic MSCs in experimental osteoarthritis contributes to the restoration of the superficial layer of cartilage, as evidenced by the formation of columns of chondrocytes in the middle layer of articular cartilage and the appearance of isogenic groups of cartilage cells with basophilic cytoplasm in the matrix, uniform articular surface. The use of the traditional method of treating rabbits using the drug Meloxicam is accompanied by incomplete chondrogenesis: part of the chondrocytes is localized in typical chambers, in some cases chondrocyte chambers did not differentiate; articular cartilage had unequal thickness, cell placement was uneven.

In vitro effects of non-steroidal anti-inflammatory drugs (Meloxicam and Flunixin Meglumine) and phytochemical (Harpagoside) on the respiratory burst of porcine polymorphonuclear neutrophils (PMNs)

In vitro effects of non-steroidal anti-inflammatory drugs (Meloxicam and Flunixin Meglumine) and phytochemical (Harpagoside) on the respiratory burst of porcine polymorphonuclear neutrophils (PMNs)

In vitro effects of non-steroidal anti-inflammatory drugs (Meloxicam and Flunixin Meglumine) and phytochemical (Harpagoside) on the respiratory burst of porcine polymorphonuclear neutrophils (PMNs)

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in veterinary medicine. Additionally, interest regarding the anti-infammatory properties of phytochemicals has emerged in recent years. In the present study, we aim to investigate the in vitro effects of meloxicam, flunixin meglumine, and harpagoside on the respiratory burst of porcine polymorphonuclear neutrophils (PMNs). We observed that harpagoside was able to suppress the respiratory burst, similarly to flunixin meglumine. Conversely, meloxicam enhanced the PMNs response. However, these effects were only detected at concentrations higher than those achievable in plasma and tissues. The present study intends to offer insights into the role of these molecules on phagocytosis mechanisms in animals to complement what is already known regarding human PMNs.

Potential Protection Effect of ER Homeostasis of N6-(2-Hydroxyethyl)adenosine Isolated from Cordyceps cicadae in Nonsteroidal Anti-Inflammatory Drug-Stimulated Human Proximal Tubular Cells.

Nonsteroidal anti-inflammatory drugs (NSAIDs) belong to a class of universally and commonly used anti-inflammatory analgesics worldwide. A diversity of drawbacks of NSAIDs have been reported including cellular oxidative stress, which in turn triggers the accumulation of unfolded proteins, enhancing endoplasmic reticulum stress, and finally resulting in renal cell damage. Cordyceps cicadae (CC) has been used as a traditional medicine for improving renal function via its anti-inflammatory effects. N6-(2-hydroxyethyl)adenosine (HEA), a physiologically active compound, has been reported from CC mycelia (CCM) with anti-inflammatory effects. We hypothesize that HEA could protect human proximal tubular cells (HK–2) from NSAID-mediated effects on differential gene expression at the mRNA and protein levels. To verify this, we first isolated HEA from CCM using Sephadex® LH–20 column chromatography. The MTT assay revealed HEA to be nontoxic up to 100 µM toward HK–2 cells. The HK–2 cells were pretreated with HEA (10–20 µM) and then insulted with the NSAIDs diclofenac (DCF, 200 µM) and meloxicam (MXC, 400 µM) for 24 h. HEA (20 µM) effectively prevented ER stress by attenuating ROS production (p < 0.001) and gene expression of ATF–6, PERK, IRE1α, CDCFHOP, IL1β, and NFκB within 24 h. Moreover, HEA reversed the increase of GRP78 and CHOP protein expression levels induced by DCF and MXC, and restored the ER homeostasis. These results demonstrated that HEA treatments effectively protect against DCF- and MXC-induced ER stress damage in human proximal tubular cells through regulation of the GRP78/ATF6/PERK/IRE1α/CHOP pathway.

Возможности терапии болевого синдрома у больных сахарным диабетом

The prevalence of lower back pain (LBP) in type 2 diabetes mellitus (DM2) is almost 2 times higher than in the similar control group (by age and gender). The association of DM2 with the severity, chronicity and recurrence of LBP was revealed. DM2 duration correlates with the severity and prevalence of degenerative-dystrophic changes. The representation of concomitant somatic pathology in patients with DM2 is significantly higher than in patients without DM2. Rational selection of the therapy regimen for LBP should be based on comorbid pathology. The molecular mechanisms of synergism of muscle relaxant (tolperizone), nonsteroidal anti-inflammatory drug (NSAID) (meloxicam), and B vitamins as part of complex pharmacotherapy of pain were analyzed. This treatment regimen has a number of benefits: lack of dependence, anti-inflammatory effect, neuroprotective and remyelinating effect, reduction of muscular hypertonus. A number of studies have shown the efficacy of such combination therapy in patients of different age groups with comorbid conditions. It does not require an increase in NSAID doses and significantly reduces the risk of adverse events (AE). The applied treatment regimen is a combination of a muscle relaxant (tolperizone), NSAID (meloxicam) and a complex of B vitamins has already demonstrated its efficacy in the treatment of LBP in patients with comorbid diseases, according to the effect on the inflammatory process indicators (in the absence of AE). KEYWORDS: diabetes mellitus, lower back pain, body mass index, nonsteroidal anti-inflammatory drugs, meloxicam, muscle relaxants, tolperizone, B vitamins. FOR CITATION: Shavlovskaya O.A., Bokova I.A., Shavlovsky N.I., Yukhnovskaya Yu.D. Possibilities of pain syndrome therapy in patients with diabetes mellitus. Russian Medical Inquiry. 2021;5(5):307–315 (in Russ.). DOI: 10.32364/2587-6821-2021-5-5-307-315.

Failed back surgery syndrome: the role of central sensitization and treatment approaches

To study a role of central sensitization (CS) in patients with Failed Back Surgery Syndrome (FBSS) after decompression of the lumbar and/or sacral roots. The study included three groups of patients: 1) early FBSS (e-FBSS, n=23), pain after surgery decreased, but continued to significantly bother the patient, or recurred in the first 6 months after surgery; 2) middle FBSS (m-FBSS, n=42), pain after surgery completely stopped, but recurred within 6-12 months; 3) late FBSS (l-FBSS, n=31), if pain relapse occurred more than 12 months later. Neurological status assessment, study of muscle trigger zones (MTZ), postoperative scar trigger zones (TZS), pain assessment according to the Visual Analogue Scale (VAS), CS assessment according to the Russian version of the Central Sensitization Inventory (CSI) were performed. Treatment included the following stages: stage 1 (non-steroidal anti-inflammatory drug (NSAID) meloxicam 15 mg 7 days); stage 2 (aminophenylbutyric acid hydrochloride (APAH) 250 mg 3 times a day 14 days); stage 3 (fluvoxamine 50 mg daily 8 weeks); stage 4 (MTZ and TZS treatment, fitness program). In addition to the previously described 96 patients, 15 patients (4 men and 11 women, aged 36-47 years) with FBSS and widespread pain, corresponding to the criteria for fibromyalgia ACTTION-APS Pain Taxonomy, who took only milnacipran 25-50 mg daily for two months (WSP-FBSS group), were studied. At baseline, CSI and VAS are as follows: CSI=72.2±6.5; VAS=58.5±8.8 in the e-FBSS group; CSI=49.2±9.0; VAS=39.5±5.3 in the m-FBSS group; CSI=18.1±5.9; VAS=18.1±5.4 in the l-FBSS group. All patients have active MTZ and TZS. The differences between MTZ and TZS subgroups were in the reproduction of pain - the appearance of pain characteristic of the patient during stimulation (pressure) of the MTZ or TZS. In the e-FBSS group, there is the low efficacy of NSAIDs, the moderate efficacy of APAH, the high efficacy of fluvoxamine. In the m-FBSS group, the moderate efficacy of NSAIDs and APAH and the high efficacy of fluvoxamine are observed. In the l-FBSS group, there is the high efficacy of NSAIDs. In the WSP-FBSS group, VAS and CSI are 58.8±9.2 mm and 75.1±8.04, respectively, before treatment, 15.51±5.1 mm (p=0.00032) and 25.6±8.2 (p=0.0002), respectively, after 2 months of treatment. In patients with FBSS, MTZ and TZS should be treated taking into account CS. The study shows the efficacy of APAH, fluvoxamine and milnacipran in the presence of CS.