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Veterinary Sciences Jun 2024The renin-angiotensin system (RAS) is increasingly being recognized to play a role in the tumor microenvironment, promoting tumor growth. Studies blocking a single part...
The renin-angiotensin system (RAS) is increasingly being recognized to play a role in the tumor microenvironment, promoting tumor growth. Studies blocking a single part of the RAS have shown mixed results, possibly due to the existence of different bypass pathways and redundancy within the RAS. As such, multimodal blockade of the RAS has been developed to exert more complete inhibition of the RAS. The aim of the present study was to assess the safety of multimodal RAS blockade in dogs. Five dogs (four with appendicular osteosarcoma, one with oral malignant melanoma) were treated with atenolol, benazepril, curcumin, meloxicam, and metformin. The dogs underwent clinical examination, blood pressure measurement, and hematology and serum biochemistry tests performed at 0, 1, 3, 6, 9, and 12 weeks, then every 3 months thereafter. End-of-life decisions were made by the owners. None of the dogs developed hypotension. One dog had intermittent vomiting during the 64 weeks it was on the trial. One dog had a one-off increase in serum SDMA(symmetrical dimethylarginine) concentration. Dogs were euthanized at weeks 3 (osteosarcoma), 10 (osteosarcoma), 17 (osteosarcoma), and 26 (oral malignant melanoma), and one dog was still alive at the end of the trial at 64 weeks (osteosarcoma). This is the first assessment of multimodal blockade of the RAS in dogs, and the results suggest it causes only mild adverse effects in some animals. The efficacy of the treatment was not assessed due to the small number of dogs. This pilot study allows for future larger studies assessing multimodal RAS blockade for the treatment of canine cancer.
PubMed: 38922022
DOI: 10.3390/vetsci11060275 -
Veterinary Sciences Jun 2024Surgical neutering in pet rabbits is common practice to prevent reproduction and associated health issues. Adequate postoperative pain management is crucial for...
Surgical neutering in pet rabbits is common practice to prevent reproduction and associated health issues. Adequate postoperative pain management is crucial for recovery, yet effective methods in clinical settings remain underexplored. This study compared the analgesic effects of carprofen and meloxicam in pet rabbits undergoing surgical neutering. Fifty rabbits of varied demographics were included, with pain assessed using the Centro Animali Non Convenzionali Rabbit Scale (CANCRS). Rabbits were allocated to receive postoperative 2 mg kg carprofen or 1 mg kg meloxicam by subcutaneous injection. Anesthesia was induced with an intramuscular combination of ketamine (20 mg kg), medetomidine (0.4 mg kg), and butorphanol (0.2 mg kg), and ovariectomy or orchiectomy were performed. The CANCRS scale was used to assess pain by evaluating the rabbit preoperatively, 6 h postoperatively, and at three time points the following day. Times of return to spontaneous feeding and fecal production were also recorded. No statistically significant difference was found between treatment groups based on CANCRS scores and resumption of food intake and fecal output. No clinically detectable adverse effects were noted. While limitations include the use of a single pain assessment scale and the absence of a placebo control group, the results suggest that both carprofen and meloxicam can be viable options in clinical practice. Further research utilizing diverse pain assessment methods is warranted to enhance understanding and optimize pain management strategies for rabbits undergoing surgical procedures.
PubMed: 38922004
DOI: 10.3390/vetsci11060257 -
Gels (Basel, Switzerland) Jun 2024The aim of this study was to obtain films based on sodium alginate (SA) for disintegration in the oral cavity. The films were prepared with a solvent-casting method, and...
The aim of this study was to obtain films based on sodium alginate (SA) for disintegration in the oral cavity. The films were prepared with a solvent-casting method, and meloxicam (MLX) as the active ingredient was suspended in a 3% sodium alginate solution. Two different solid-dosage-form additives containing different disintegrating agents, i.e., VIVAPUR 112 (MCC; JRS Pharma, Rosenberg, Germany) and Prosolve EASYtabs SP (MIX; JRS Pharma, Rosenberg, Germany), were used, and four different combinations of drying time and temperature were tested. The influence of the used disintegrant on the properties of the ODFs (orodispersible films) was investigated. The obtained films were studied for their appearance, elasticity, mass uniformity, water content, meloxicam content and, finally, disintegration time, which was studied using two different methods. The films obtained with the solvent-casting method were flexible and homogeneous in terms of MLX content. Elasticity was slightly better when MIX was used as a disintegrating agent. However, these samples also revealed worse uniformity and mechanical durability. It was concluded that the best properties of the films were achieved using the mildest drying conditions. The type of the disintegrating agent had no effect on the amount of water remaining in the film after drying. The water content depended on the drying conditions. The disintegration time was not affected by the disintegrant type, but some differences were observed when various drying conditions were applied. However, regardless of the formulation type and manufacturing conditions, the analyzed films could not be classified as fast disintegrating films, as the disintegration time exceeded 30 s in all of the tested formulations.
PubMed: 38920926
DOI: 10.3390/gels10060379 -
Frontiers in Veterinary Science 2024Diagnosing and treating lameness in horses is essential to improving their welfare. In equine orthopedic practice, infrared thermography (IRT) can indirectly detect...
INTRODUCTION
Diagnosing and treating lameness in horses is essential to improving their welfare. In equine orthopedic practice, infrared thermography (IRT) can indirectly detect soreness. Non-steroidal anti-inflammatory drugs can treat painful and inflammatory processes in horses. Using IRT, the efficacy of meloxicam (Maxicam Gel) was evaluated in pre-treating transient synovitis in horses induced by a middle carpal joint injection of lipopolysaccharides (LPS) from 055:B5 at a dose of 10 endotoxin units.
METHODS
In a cross-over design, six healthy horses were randomly assigned to receive either 0.6 mg/kg of oral Maxicam Gel (MAXVO) or a mock administration (control group, C) following a two-week washout period. IRT of the middle carpal joint, visual lameness assessment and joint circumference were recorded over time. Clinical and hematological evaluations were performed. Synovial fluid aspirates were analyzed for total nucleated cell count, total protein, and prostaglandin E. A mixed effects analysis of variance was performed for repeated measures over time, followed by Tukey's test. A multinomial logistic regression was conducted to determine whether there is a relationship between a thermography temperature change and the lameness score.
RESULTS
There were no changes in joint circumference. The MAXVO group showed a lower rectal temperature 4 h after synovitis induction. The C group presented an increase in neutrophils and a decrease in total hemoglobin and hematocrit 8 h after induction. No changes were observed in the synovial fluid between groups. The horses that received meloxicam did not show clinically significant lameness at any time, while the C group showed an increase in lameness 2, 4, and 8 h after synovitis induction.
DISCUSSION
IRT indicated that the skin surface temperature of the middle carpal joint was lower in horses who received meloxicam, suggesting a reduction in the inflammatory process induced by LPS. It was observed that the maximum temperature peaks in the dorsopalmar and lateropalmar positions can be utilized to predict the severity of lameness, particularly when the temperature rises above 34°C. Horses pre-treated with meloxicam showed either reduced or no indication of mild to moderate pain and presented a lowehr thermographic temperature, which indicates the effectiveness of Maxicam Gel as an anti-inflammatory.
PubMed: 38919154
DOI: 10.3389/fvets.2024.1399815 -
Molecules (Basel, Switzerland) May 2024Organic-inorganic hybrids represent a good solution to improve the solubility and dissolution rates of poorly soluble drugs whose number has been increasing in the last...
Organic-inorganic hybrids represent a good solution to improve the solubility and dissolution rates of poorly soluble drugs whose number has been increasing in the last few years. One of the most diffused inorganic matrices is hydroxyapatite (HAP), which is a biocompatible and osteoconductive material. However, the understanding of the hybrids' functioning mechanisms is in many cases limited; thus, thorough physicochemical characterizations are needed. In the present paper, we prepared hybrids of pure and Mg-doped hydroxyapatite with meloxicam, a drug pertaining to the Biopharmaceutical Classification System (BCS) class II, i.e., drugs with low solubility and high permeability. The hybrids' formation was demonstrated by FT-IR, which suggested electrostatic interactions between HAP and drug. The substitution of Mg in the HAP structure mainly produced a structural disorder and a reduction in crystallite sizes. The surface area of HAP increased after Mg doping from 82 to 103 mg as well as the pore volume, justifying the slightly high drug amount adsorbed by the Mg hybrid. Notwithstanding the low drug loading on the hybrids, the solubility, dissolution profiles and wettability markedly improved with respect to the drug alone, particularly for the Mg doped one, which was probably due to the main distribution of the drug on the HAP surface.
PubMed: 38893294
DOI: 10.3390/molecules29112419 -
Frontiers in Veterinary Science 2024Serum symmetric dimethylarginine (SDMA) and creatinine are commonly used biomarkers of renal function in cats. We hypothesize that the serum analytes creatinine and SDMA...
INTRODUCTION
Serum symmetric dimethylarginine (SDMA) and creatinine are commonly used biomarkers of renal function in cats. We hypothesize that the serum analytes creatinine and SDMA are equally effective at detecting impaired renal function caused by meloxicam-induced renal injury in cats. Our primary objective was to compare serum concentrations of SDMA and creatinine in cats before, during, and after induction of renal injury from repeated dosages of meloxicam in the context of a small pilot study.
METHODS
This follow-up study results from data collected in a well-controlled study that included 12 healthy female adult purpose-bred cats. Cats in the treatment group received meloxicam 0.3 mg/kg subcutaneously (SC) every 24 h for 31 days. Cats in the control group received saline (0.1 mL SC). Renal injury was defined as the presence of tubular damage, basement membrane damage, and/or interstitial inflammation in histological sections of kidney tissue. Serum creatinine and SDMA concentration were measured every 4 days.
RESULTS
In the control group, no cats developed renal azotemia. In the treatment group, four out of six cats developed elevated serum creatinine and histopathological evidence of renal injury. Three of these cats developed an elevation in serum SDMA. The time to the development of renal azotemia using serum creatinine or SDMA was not significantly different ( > 0.05).
DISCUSSION
In this pilot study, there was no evidence that serum SDMA was superior to serum creatinine at detecting impaired renal function caused by meloxicam-induced renal injury in cats.
PubMed: 38812562
DOI: 10.3389/fvets.2024.1395505 -
Journal of Comparative Pathology May 2024Reports of primary cardiovascular disease in goats are rare and most commonly include ventricular septal defect, valvular endocarditis, traumatic pericarditis, ionophore...
Reports of primary cardiovascular disease in goats are rare and most commonly include ventricular septal defect, valvular endocarditis, traumatic pericarditis, ionophore poisoning and nutritional cardiomyopathies. We now report the pathological findings in a 67 kg, 6-year-old, adult female Boer goat that presented with neurological signs (ie, head pressing, unsteadiness and paddling) and hyperthermia 2 days prior to death. Lack of therapeutic response to meloxicam and penicillin‒streptomycin and poor prognosis led to euthanasia of the animal. At necropsy, the main findings included severe aortic dissection with luminal thrombosis and stenosis, and pulmonary congestion and oedema. Histological examination of the aorta revealed severe chronic granulomatous and fibrosing dissecting aortitis with mineralization. Bacterial culture of the affected aortic segment resulted in isolation of a profuse growth of Pasteurella multocida and a moderate growth of Staphylococcus spp. Histopathological findings in the central nervous system were consistent with neurolisteriosis.
Topics: Animals; Pasteurella multocida; Goats; Goat Diseases; Pasteurella Infections; Female; Staphylococcal Infections; Aortic Dissection
PubMed: 38759507
DOI: 10.1016/j.jcpa.2024.04.002 -
Frontiers in Molecular Neuroscience 2024Pain mostly arises because specialized cells called nociceptors detect harmful or potentially harmful stimuli. In lower animals with less convoluted nervous system,...
INTRODUCTION
Pain mostly arises because specialized cells called nociceptors detect harmful or potentially harmful stimuli. In lower animals with less convoluted nervous system, these responses are believed to be purely nociceptive. Amongst invertebrate animal models, planarians are becoming popular in a wide range of pharmacological and behavioral studies beyond the field of regeneration. Recent publications led the way on pain studies by focusing on nociceptive behaviors such as the 'scrunching' gait displayed under various noxious stimuli, as opposed to the 'gliding' gait planarians usually adopt in normal conditions.
METHODS
In this study, we adapted commonly used nociceptive tests to further explore nociception in planarians of the species . By using behavioral analysis in open fields and place preferences, we managed to set up chemical, thermal and mechanical nociceptive tests. We also adapted RNA interference protocols and explored the effects of knocking down TRPA1 ion channels, one of the main effectors of chemically and thermally-induced nociceptive responses in vertebrates.
RESULTS
Consequently, we demonstrated the reliability of the scrunching gait in this planarian species, which they displayed in a dose-dependent manner when exposed to the irritant AITC. We also showed that suppressing the expression of TRPA1 ion channels completely suppressed the scrunching gait, demonstrating the involvement of TRPA1 nociceptors in this nociceptive reaction. Besides, we also explored the effects of two common analgesics that both displayed strong antinociceptive properties. First, morphine reduced the chemically-induced nociceptive scrunching gaits by more than 20% and shifted the of the dose-response curve by approximately 10 μM. Secondly, the NSAID meloxicam drastically reduced chemically-induced scrunching by up to 60% and reduced heat avoidance in place preference tests.
DISCUSSION
Thus, we managed to characterize both behavioral and pharmacological aspects of 's nociception, further developing the use of planarians as a replacement model in pain studies and more globally the study of invertebrate nociception.
PubMed: 38751713
DOI: 10.3389/fnmol.2024.1368009 -
Journal of Clinical Medicine Apr 2024: In the context of the current opioid crisis, non-pharmacologic approaches to pain management have been considered important alternatives to the use of opioids or... (Review)
Review
: In the context of the current opioid crisis, non-pharmacologic approaches to pain management have been considered important alternatives to the use of opioids or analgesics. Advancements in nano and quantum technology have led to the development of several nanotransporters, including nanoparticles, micelles, quantum dots, liposomes, nanofibers, and nano-scaffolds. These modes of nanotransporters have led to the development of new drug formulations. In pain medicine, new liposome formulations led to the development of DepoFoam™ introduced by Pacira Pharmaceutical, Inc. (Parsippany, NJ, USA). This formulation is the base of DepoDur™, which comprises a combination of liposomes and extended-release morphine, and Exparel™, which comprises a combination of liposomes and extended-release bupivacaine. In 2021, Heron Therapeutics (San Diego, CA, USA) created Zynrelef™, a mixture of bupivacaine and meloxicam. Advancements in nanotechnology have led to the development of devices/patches containing millions of nanocapacitors. Data suggest that these nanotechnology-based devices/patches reduce acute and chronic pain. : Google and PubMed searches were conducted to identify studies, case reports, and reviews of medical nanotechnology applications with a special focus on acute and chronic pain. This search was based on the use of keywords like nanotechnology, nano and quantum technology, nanoparticles, micelles, quantum dots, liposomes, nanofibers, nano-scaffolds, acute and chronic pain, and analgesics. This review focuses on the role of nanotechnology in acute and chronic pain. : (1) Nanotechnology-based transporters. DepoDur™, administered epidurally in 15, 20, or 25 mg single doses, has been demonstrated to produce significant analgesia lasting up to 48 h. Exparel™ is infiltrated at the surgical site at the recommended dose of 106 mg for bunionectomy, 266 mg for hemorrhoidectomy, 133 mg for shoulder surgery, and 266 mg for total knee arthroplasty (TKA). Exparel™ is also approved for peripheral nerve blocks, including interscalene, sciatic at the popliteal fossa, and adductor canal blocks. The injection of Exparel™ is usually preceded by an injection of plain bupivacaine to initiate analgesia before bupivacaine is released in enough quantity from the depofoarm to be pharmacodynamically effective. Finally, Zynrelef™ is applied at the surgical site during closure. It was initially approved for open inguinal hernia, abdominal surgery requiring a small-to-medium incision, foot surgery, and TKA. (2) Nanotechnology-based devices/patches. Two studies support the use of nanocapacitor-based devices/patches for the management of acute and chronic pain. A randomized study conducted on patients undergoing unilateral primary total knee (TKA) and total hip arthroplasty (THA) provided insight into the potential value of nanocapacitor-based technology for the control of postoperative acute pain. The results were based on 2 studies, one observational and one randomized. The observational study was conducted in 128 patients experiencing chronic pain for at least one year. This study suggested that compared to baseline, the application of a nanocapacitor-based Kailo™ pain relief patch on the pain site for 30 days led to a time-dependent decrease in pain and analgesic use and an increase in well-being. The randomized study compared the effects of standard of care treatment to those of the same standard of care approach plus the use of two nanocapacitor-based device/patches (NeuroCuple™ device) placed in the recovery room and kept in place for three days. The study demonstrated that the use of the two NeuroCuple™ devices was associated with a 41% reduction in pain at rest and a 52% decrease in the number of opioid refills requested by patients over the first 30 days after discharge from the hospital. : For the management of pain, the use of nano-based technology has led to the development of nano transporters, especially focus on the use of liposome and nanocapacitors. The use of liposome led to the development of DepoDur™, bupivacaine Exparel™ and a mixture of bupivacaine and meloxicam (Zynrelef™) and more recently lidocaine liposome formulation. In these cases, the technology is used to prolong the duration of action of drugs included in the preparation. Another indication of nanotechnology is the development of nanocapacitor device or patches. Although, data obtained with the use of nanocapacitors are still limited, evidence suggests that the use of nanocapacitors devices/patches may be interesting for the treatment of both acute and chronic pain, since the studies conducted with the NeuroCuple™ device and the based Kailo™ pain relief patch were not placebo-controlled, it is clear that additional placebo studies are required to confirm these preliminary results. Therefore, the development of a placebo devices/patches is necessary. : Increasing evidence supports the concept that nanotechnology may represent a valuable tool as a drug transporter including liposomes and as a nanocapacitor-based device/patch to reduce or even eliminate the use of opioids in surgical patients. However, more studies are required to confirm this concept, especially with the use of nanotechnology incorporated in devices/patches.
PubMed: 38731140
DOI: 10.3390/jcm13092611 -
Clinical and Translational Science May 2024Fexuprazan, a novel potassium-competitive acid blocker, is expected to be used for the prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) induced ulcer. This... (Randomized Controlled Trial)
Randomized Controlled Trial
Fexuprazan, a novel potassium-competitive acid blocker, is expected to be used for the prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) induced ulcer. This study aimed to evaluate pharmacokinetic (PK) interactions between fexuprazan and NSAIDs in healthy subjects. A randomized, open-label, multicenter, six-sequence, one-way crossover study was conducted in healthy male subjects. Subjects randomly received one of the study drugs (fexuprazan 40 mg BID, celecoxib 200 mg BID, naproxen 500 mg BID, or meloxicam 15 mg QD) for 5 or 7 days in the first period followed by the combination of fexuprazan and one of NSAIDs for the same days and the perpetrator additionally administered for 1-2 days in the second period. Serial blood samples for PK analysis were collected until 48- or 72-h post-dose at steady state. PK parameters including maximum plasma concentration at steady state (C) and area under plasma concentration-time curve over dosing interval at steady state (AUC) were compared between monotherapy and combination therapy. The PKs of NSAIDs were not significantly altered by fexuprazan. For fexuprazan, differences in PK parameters (22% in C, 19% in AUC) were observed when co-administered with naproxen, but not clinically significant. The geometric mean ratio (90% confidence interval) of combination therapy to monotherapy for C and AUC was 1.22 (1.02-1.46) and 1.19 (1.00-1.43), respectively. There were no significant changes in the systemic exposure of fexuprazan by celecoxib and meloxicam. Fexuprazan and NSAIDs did not show clinically meaningful PK interactions.
Topics: Humans; Male; Anti-Inflammatory Agents, Non-Steroidal; Adult; Drug Interactions; Young Adult; Cross-Over Studies; Healthy Volunteers; Area Under Curve; Meloxicam; Naproxen; Celecoxib; Middle Aged
PubMed: 38700290
DOI: 10.1111/cts.13798