Development of a novel intramuscular liposomal injection for advanced meloxicam delivery: Preparation, characterization, in vivo pharmacokinetics, pharmacodynamics, and pain assessment in an orthopedic pain model.

Pain produces several physiological, and degenerative complications. This study aimed to formulate meloxicam (MLX) in liposomes to increase solubility and deliver MLX in a controlled manner to overcome its poor aqueous solubility and relatively short t1/2 problems. Liposomes were prepared by thin film hydration followed by ultrasonication. Tests for characterizing formulations included particle size, span, entrapment efficiency, drug loading, stability, differential scanning calorimetry (DSC), Fourier transformation infrared (FT-IR) spectroscopy, morphology, in vitro release, release kinetics mathematical modeling, and an in vivo pain model in dogs undergoing orthopedic surgeries, followed by in vivo pharmacokinetics, pharmacodynamics, and pain assessment studies in comparison to the reference standard, Mobitil®. Liposomal MLX had a particle size of around 100 nm, 82 % entrapment efficiency, and 4.62 % drug loading. Stability studies, DSC, and FT-IR spectroscopy indicated that liposomes were highly stable. The formulation showed an improved in vitro controlled release pattern and an enhanced in vivo pharmacokinetic behavior as manifested by higher t1/2 and AUC0 - 24 and lower Cl/F in comparison to Mobitil®. The pharmacodynamics study and pain scales demonstrated liposomal MLX managed postoperative pain better than Mobitil®. In conclusion, the incorporation of MLX in liposomes increased its solubility and stability, as well as its pain management properties.

Correction: Mahmoud et al. Neurotoxic Effect of Fipronil in Male Wistar Rats: Ameliorative Effect of L-Arginine and L-Carnitine. Biology 2021, 10, 682.

In the original publication [...].

Reconstruction of a partial esophageal defect using tunica vaginalis and buccal mucosa autograft: an experimental study in mongrel dogs.

In veterinary clinics, esophageal reconstruction is essential in many clinical situations. In this study, two autografts, the tunica vaginalis (TV) and the buccal mucosa (BM), were proposed to reconstruct a semi-circumferential cervical esophageal defect in dogs. This study aimed to verify whether these two grafts could successfully patch esophageal defects. Twelve male mongrel dogs were divided into two groups. Following cervical esophagoplasty, the defective area was patched with either a TV or a BM graft. Comprehensive clinical, serum biochemical, and histological analyses were performed to evaluate the two grafts. Throughout the study (120 days), the dogs survived the procedure well with minor complications. The lumen of the patched areas was covered with mucosa, with slight scar retraction. Compared with that of the natural esophagus, the average relative luminal diameter was not significantly decreased. Importantly, the measured cortisol and inflammatory marker levels returned to the preoperative levels after 14 days. Although histological examination revealed that both grafts repaired the esophageal defect with complete re-epithelialization, the BM graft showed a histological structure similar to that of the natural esophagus. Both grafts effectively repaired the esophageal defect with minor complications; therefore, both are recommended as promising low-cost clinical alternatives for cervical esophagoplasty in dogs.

Evaluation of Cadmium or Lead Exposure with Nannochloropsis oculata Mitigation on Productive Performance, Biochemical, and Oxidative Stress Biomarkers in Barki Rams.

This study was designed to determine the lead or cadmium exposure of Barki rams and the beneficial role of Nannochlorposis oculata (N. oculata) 4% as a feed supplement, as well as its mitigating role against these elements' impacts concerning performance, biochemical markers of liver enzymes and kidney function, thyroid hormone activity, and oxidative stress markers. Six groups of 36 Barki rams (33.63 ± 1.29 kg) were divided into G1: which served as control; G2: was given 4% dietary N. oculata; G3: was given oral 1 mg/kg cadmium chloride; G4: was given 5 mg/kg/day lead acetate; G5: was given oral 1 mg/kg cadmium chloride and 4% dietary N. oculata, and G6: was given oral 5 mg/kg/day lead acetate and 4% dietary N. oculata; and treatments were continued for 60 days. Cadmium and lead-exposed groups exhibited lower and weaker weight gain as well as feed conversion ratio, respectively, than the control and other groups. Additionally, levels of T3, T4, total proteins, albumin, and glutathione (GSH) were significantly reduced in both G3 and G4 compared to control. However, urea, creatinine, ALT, AST, total cholesterol, triglycerides, protein carbonyl content (PCC), and malondialdehyde (MDA) were significantly increased (P ≤ 0.05) in cadmium and lead-exposed groups. Dietary N. oculata (4%) improves serum proteins, creatinine, urea, T4, and oxidative stress indicators as compared to the control group. Finally, 4% dietary N. oculata greatly enhances the investigated parameters in terms of performance, thyroid hormones, serum biochemical, and antioxidant activity and may assist in reducing the endocrine disrupting effects of Pb and Cd.

Selective Calpain Inhibition Improves Functional and Histopathological Outcomes in a Canine Spinal Cord Injury Model.

Calpain activation has been implicated in various pathologies, including neurodegeneration. Thus, calpain inhibition could effectively prevent spinal cord injury (SCI) associated with neurodegeneration. In the current study, a dog SCI model was used to evaluate the therapeutic potential of a selective calpain inhibitor (PD150606) in combination with methylprednisolone sodium succinate (MPSS) as an anti-inflammatory drug. SCI was experimentally induced in sixteen mongrel dogs through an epidural balloon compression technique. The dogs were allocated randomly into four groups: control, MPSS, PD150606, and MPSS+PD150606. Clinical evaluation, serum biochemical, somatosensory evoked potentials, histopathological, and immunoblotting analyses were performed to assess treated dogs during the study. The current findings revealed that the combined administration of MPSS+PD150606 demonstrated considerably lower neuronal loss and microglial cell infiltration than the other groups, with a significant improvement in the locomotor score. The increased levels of inflammatory markers (GFAP and CD11) and calcium-binding proteins (Iba1 and S100) were significantly reduced in the combination group and to a lesser extent in MPSS or PD150606 treatment alone. Interestingly, the combined treatment effectively inhibited the calpain-induced cleavage of p35, limited cdk5 activation, and inhibited tau phosphorylation. These results suggest that early MPSS+PD150606 therapy after acute SCI may prevent subsequent neurodegeneration via calpain inhibition.

Dietary Parsley Seed Mitigates Methomyl-Induced Impaired Growth Performance, Hemato-Immune Suppression, Oxidative Stress, Hepato-Renal Damage, and Pseudomonas aeruginosa Susceptibility in Oreochromis niloticus.

The present experiment investigated the potential protective role of parsley (Petroselinum crispum) seed meal (PSM) in alleviating methomyl (MET)-adverse impacts on growth, whole-body composition, hematological indicators, hepatorenal function, immune response, oxidative status, and disease resistance to Pseudomonas aeruginosa. For this purpose, 225 healthy Nile tilapia (Oreochromis niloticus) were allotted into five groups (45 fish/group in triplicate). One group was reared in clean water and fed a non-supplemented basal diet, while the other groups were exposed to 20.39 µg L-1 MET and fed a non-fortified basal diet or basal diets supplemented with 0.5, 1.0, or 2.0% of PSM for 60 days. The obtained data revealed significantly lower weight gain, feed intake, and specific growth rate, but higher feed conversion ratio and decreases in crude protein, lipid, and ash contents in the MET-exposed fish. Anemia, leukopenia, lymphocytopenia, and esonipenia were also obvious. Furthermore, MET-exposed fish had significantly higher serum levels of hepatic enzymes and renal damage products. Nevertheless, there was a significant depletion of enzymatic and non-enzymatic antioxidants and increased malondialdehyde, myeloperoxidase, and tumor necrosis factor-α levels in MET-exposed fish. The MET exposure significantly depressed lysozyme activity, nitric oxide, complement3, acetylcholinesterase activity, total proteins, globulin, and albumin levels in O. niloticus serum. Furthermore, pathological alterations in the liver and kidney were noted. The relative percentage of survival rate in MET-exposed fish was dramatically reduced on day 14 post-challenge with P. aeruginosa. The inclusion of PSM, on the other hand, greatly alleviated most of the MET-related negative effects. Taken together, the dietary intervention with PSM has a promising role in alleviating MET-deleterious impacts, rendering parsley seeds a viable aqua feed additive for O. niloticus.

Immune-antioxidant trait, Aeromonas veronii resistance, growth, intestinal architecture, and splenic cytokines expression of Cyprinus carpio fed Prunus armeniaca kernel-enriched diets.

Currently, the intervention of plant by-products in the fish diet has gained tremendous attention owing to the economic and high nutritious value. The current study is a pioneer attempt to incorporate the apricot, Prunus armeniaca kernel powder (PAKP) into the Common carp, Cyprinus carpio diets, and assess its efficacy on growth, digestion, intestinal morphology, immunity, antioxidant capacity, and splenic cytokines expression, besides the antibacterial role against Aeromonas veronii infection. Apparently healthy fish (N = 120) with an initial body weight of 24.76 ± 0.03g were allotted in 12 glass aquaria (60 L) and randomly distributed into four groups (triplicates, 10 fish/aquarium). The control group (PAKP0) was fed a basal diet without additives. The second, third, and fourth groups were provided PAKP diets with various concentrations (2.5 (PAKP2.5), 5 (PAKP5), and 10 g kg-1 (PAKP10)) respectively. After 60 days (feeding trial), sub-samples of the fish (12 fish/group) were intraperitoneally injected with 1 × 107 CFU mL-1 of A. veronii. Results revealed that body weight gain, feed conversion ratio, and specific growth rates were significantly augmented in the PAKP10 group in comparison to the other groups. The dietary inclusion of PAKP at all concentrations boosted the digestive capacity and maintained the intestinal morphology (average villus length, villus width, and goblet cells count) with a marked improvement in PAKP10. Moreover, fish fed on PAKP10 followed by PAKP5 then PAKP2.5 diets had noticeably elevated values of immunological biomarkers (IgM, antiprotease, and lysozyme activity) and antioxidant capabilities (the total antioxidant capacity, superoxide dismutase, and reduced glutathione) as well as significant up-regulation of immune and antioxidant-related genes (TGF-ß2, TLR-2, TNF-α, IL-10, SOD, GPx, and GSS). Fourteen days post-infection with A. veronii, the highest relative percentage survival of fish was observed in PAKP10 (83.33%), followed by PAKP5 (66.67%), and PAKP2.5 (50%). Our results indicated that a dietary intervention with PAKP could promise growth, digestion, immunity, and protect C. carpio against A. veronii infection in a dose-dependent manner. This offers a framework for future application of such seeds as a growth promotor, immune-stimulant, and antioxidant, besides an alternative cheap therapeutic antibacterial agent for sustaining the aquaculture industry.

Augmentation cystoplasty in dogs: A comparative study of different tunica vaginalis grafts.

In veterinary practice, numerous urological disorders that cause bladder dysfunction necessitate augmentation cystoplasty (AC). The purpose of this study is to evaluate the dog tunica vaginalis allograft (DTVA), sheep tunica vaginalis xenograft (STVX) and sheep tunica vaginalis decellularized extracellular matrix (STVDEM) as graft materials for urinary bladder (UB) reconstruction following a 45±5% cystectomy model in dogs. In this study, 18 adult apparently healthy mongrel dogs of both sexes were divided into three groups (6 dogs each): the DTVA group, the STVX group, and the STVDEM group. The evaluation of the AC in different groups was carried out using clinical, hematological, serum biochemical, urine, ultrasonographic, retrograde positive cystogram, and histopathological analysis all over the study period of 12 weeks. The dogs in all groups survived the procedures, except three dogs died from both STVX and DTVA groups. The mean bladder capacity indicated that the DTVA and STVX groups had regained 82.22% and 68.62%, respectively, of their preoperative baseline capacity. Interestingly, the STVDEM group's bladder capacity increased to 113.70%. Although histological analysis revealed that the three grafts successfully rebuilt the bladder wall, the STVDEM demonstrated well-organized and well-differentiated epithelial and muscular tissues that resembled, but were not identical to, native UB tissues. As a result, STVDEM is proposed as an ideal and potential acellular graft for UB reconstruction in dogs, whereas DTVA and STVX could be employed in emergencies requiring UB reconstruction.

Neurotoxic Effect of Fipronil in Male Wistar Rats: Ameliorative Effect of L-Arginine and L-Carnitine.

The ameliorative effect of L-arginine (LA) and L-carnitine (LC) against fipronil (FPN)-induced neurotoxicity was explored. In this case, 36 adult male rats were randomly divided into six groups: group I received distilled water, group II received 500 mg/kg LA, group III received 100 mg/kg LC, group IV received 4.85 mg/kg FPN, group V received 4.85 mg/kg FPN and 500 mg/kg LA and group VI received 4.85 mg/kg FPN and 100 mg/kg LC for 6 weeks. Cognitive performance was assessed using Barnes maze (BM). Serum corticosterone, brain total antioxidant capacity (TAC), malondialdehyde (MDA) and dopamine were measured. Histopathology and immunohistochemistry of ionized calcium-binding adaptor (Iba-1), doublecortin (DCX) and serotonin (S-2A) receptors were performed. Fipronil induced noticeable deterioration in spatial learning and memory performance. In addition, FPN significantly (p < 0.05) diminished brain antioxidant defense system and dopamine coincide with elevated serum corticosterone level. Histopathological examination revealed degenerative and necrotic changes. Furthermore, Iba-1 and DCX were significantly expressed in cortex and hippocampus whereas S-2A receptors were significantly lowered in FPN group. However, administration of LA or LC alleviated FPN-induced deteriorations. In conclusion, LA and LC could be prospective candidates for mitigation of FPN-induced neurotoxicity via their antioxidant, anti-inflammatory and neuropotentiating effects.

Subclinical endometritis and postpartum ovarian resumption in respect to TNF-α, IL-8 and CRP in Egyptian buffaloes.

The study was carried out to find the relation between subclinical endometritis (SCE) and postpartum (pp.) ovarian resumption as well as to evaluate serum and endometrial TNF-α, IL-8 and serum CRP in buffaloes with and without SCE. Thirty-nine pluriparous buffaloes at the 3rd (W3), 5th (W5) and 7th (W7) week pp. were involved in this experiment. The parity of the buffaloes ranged from 4 to 8 with an average 5.8±0.2. Subclinical endometritis was diagnosed by the percentage of polymorphonuclear cells (PMNs) in uterine cytology obtained from endometrial cytobrush at W5 and W7. The cut-off point of PMNs% in buffaloes for SCE was ≥ 6% at W5 or ≥ 4% at W7. According to PMNs%, buffaloes were divided into SCE group (n=27) and non-SCE group (n=12). Ovarian cyclicity was monitored by rectal palpation, ultrasonography and progesterone assay at W3, W5 and W7. Serum and endometrial TNF-α, IL-8 and serum CRP were estimated at W5 and W7. Buffaloes with SCE (55.6%) showed delayed ovarian activity as compared to non-SCE (16.7%) animals (P=0.036). Significant increase in serum cytokines and CRP levels were detected at W5 (P ˂0.05) and W7 (P <0.01) in SCE buffaloes as compared to non-SCE. Endometrial levels of cytokines were significantly (P ˂0.05) elevated in SCE buffaloes. Serum and endometrial cytokines showed significant positive correlation. Furthermore, levels of TNF-α, IL-8 and CRP exhibited significant positive correlation with PMNs%. In conclusion, SCE delayed postpartum ovarian cyclicity in buffaloes. Moreover, TNF-α, IL-8 and CRP assessments could be efficient tools in prediction of SCE in buffaloes.

Hormonal and metabolic profiles related to placental retention with emphasis on oxidative stress and serotonin receptors in pluriparous buffaloes.

This study was designed to investigate the hormonal and metabolic factors associated with placental retention in buffaloes with respect to the roles of oxidative stress biomarkers and serotonin receptors. Blood samples were collected at weeks 3, 2 and 1 pre-partum and at calving from 37 buffaloes; thirty normally dropped their placentae (Non-RFM group) and 7 dropped their placentae after 12 hr post-calving (RFM group). Serum progesterone (P4 ), oestradiol, cortisol, non-esterified fatty acids (NEFA), beta-hydroxybutyric acid (BHBA), antioxidant/oxidant biomarkers and mineral concentrations were assessed. Histopathology and histochemistry were implemented to detect collagen in foetal placental tissues. Immunohistochemistry for serotonin receptors in placental tissues was performed. Significant elevations in P4 , cortisol, NEFA, BHBA and oxidative biomarkers concentrations were observed in the RFM group. However, oestradiol, antioxidants and mineral concentrations were significantly lower in RFM buffaloes than Non-RFM group. Histopathological examination revealed degenerative changes and necrosis in retained placental tissue compared with that in normal placental tissues. Serotonin receptors were significantly expressed with collagen condensation in retained placental tissues. Furthermore, inferior reproductive performance was pronounced in the retained group. In conclusion, retained foetal membranes in buffaloes were associated with hormonal imbalance, metabolic perturbation, oxidative stress, serotonin receptor upregulation and markedly reduced fertility indices.

Associations between metabolic profiles, post-partum delayed resumption of ovarian function and reproductive performance in Egyptian buffalo: Roles of IGF-1 and antioxidants.

This study was conducted on 47 pluriparous pregnant Egyptian buffalo. Body condition score (BCS) was classified and blood samples were collected pre-partum and post-partum for estimation of IGF-1, hormonal, metabolic and antioxidants values. There was palpation per rectum and ultrasonography in addition to quantitation of progesterone (P4) and estradiol-17ß (E-17ß) for monitoring post-partum ovarian resumption. Reproductive indices were calculated 60, 90, 120 and 150 days post-partum. Based on the concentrations of P4 and E-17ß, buffalo were divided into ovulatory and non-ovulatory groups. The P4 and E-17ß were greater (P < 0.001) in ovulatory compared to non-ovulatory buffalo. The BCS and IGF-1 post-partum were greater (P =  0.024; 0.001, respectively) in ovulatory than non-ovulatory buffalo. Glucose and albumin were greater during pre- (P < 0.001; 0.013) and post-partum (P = 0.005; 0.003) periods in ovulatory than non-ovulatory buffalo. Post-partum, NEFA and BHBA concentrations were greater (P < 0.001) in non-ovulatory than ovulatory buffalo. The BUN concentrations were greater (P =  0.002) in non-ovulatory buffalo during pre- and post-partum periods. There were differences in GSH and SOD concentrations between groups (P < 0.001; 0.002, respectively). The BCS, albumin, IGF-1, GSH and SOD concentrations post-partum were negatively correlated with the delay of post-partum ovulation. The post-partum NEFA and BHBA concentrations, however, were positively correlated with delayed post-partum ovulation. Ovulatory buffalo had fewer (P < 0.01) days non-pregnant and for calving intervals as well as greater pregnancy rates than non-ovulatory buffalo. In conclusion, buffalo with delayed post-partum ovarian resumption were prone to have negative energy balance.

Cancer: Thymoquinone antioxidant/pro-oxidant effect as potential anticancer remedy.

Recently, there is growing interest in the natural bioactive components having anticancer activity. Thymoquinone (TQ), the principle active constituent of black seed (Nigella sativa), has promising properties including anticancer and chemosensitizing peculiarities. The anticancer power of TQ is accomplished by several aspects; including promotion of apoptosis, arrest of cell cycle and ROS generation. In addition, it boosts the immune system and lessens the side effects associated with traditional anticancer therapy. TQ also controls angiogenesis and cancer metastasis. This review focuses on the potential aspects and mechanisms by which TQ acquires its actions.