Mel Group Research Articles

Melatonin in Newborn Infants Undergoing Surgery: A Pilot Study on Its Effects on Postoperative Oxidative Stress

Surgery is frequently associated with excessive oxidative stress. Melatonin acts as an antioxidant and transient melatonin deficiency has been described in neonatal surgical patients. This randomized, blinded, prospective pilot study tested the hypothesis that oral melatonin supplementation in newborn infants undergoing surgery is effective in reducing perioperative oxidative stress. A total of twenty-three newborn infants requiring surgery were enrolled: 10 received a single dose of oral melatonin 0.5 mg/kg in the morning, before surgery (MEL group), and 13 newborns served as the control group (untreated group). Plasma concentrations of melatonin, Non-Protein-Bound Iron (NPBI), Advanced Oxidation Protein Products (AOPP), and F2-Isoprostanes (F2-IsoPs) were measured. Both in the pre- and postoperative period, melatonin concentrations were significantly higher in the MEL group than in the untreated group (preoperative: 1265.50 ± 717.03 vs. 23.23 ± 17.71 pg/mL, p < 0.0001; postoperative: 1465.20 ± 538.38 vs. 56.47 ± 37.18 pg/mL, p < 0.0001). Melatonin significantly increased from the pre- to postoperative period in the untreated group (23.23 ± 17.71 vs. 56.47 ± 37.18 pg/mL; pg/mL p = 0.006). In the MEL group, the mean blood concentrations of NPBI, F2-IsoPs, and AOPP significantly decreased from the pre- to the postoperative period (4.69 ± 3.85 vs. 1.65 ± 1.18 micromol/dL, p = 0.049; 128.40 ± 92.30 vs. 50.25 ± 47.47 pg/mL, p = 0.037 and 65.18 ± 15.50 vs. 43.98 ± 17.92 micromol/dL, p = 0.022, respectively). Melatonin concentration increases physiologically from the pre- to the postoperative period, suggesting a defensive physiologic response to counteract oxidative stress. The administration of exogenous melatonin in newborn infants undergoing surgery reduces lipid and protein peroxidation in the postoperative period, showing a potential role in protecting babies from the deleterious consequences of oxidative stress.

Immunohistochemical Evidence of Melatonin Protection on Lung Tissue During Chemotherapy

The present study investigated the possible protective effects of melatonin on Bleomycin, Cisplatin and etoposide (BEP) chemotherapy regimens using immunohistochemistry. Forty male Wistar rats were divided into four groups of ten as; group 1 as untreated control; group 2 as BEP group which received the three cycles of 21 days’ regimen each of 0.5¥ dose levels ofBEP (bleomycin 0.75 mg/kg, etoposide 7.5 mg/kg and cisplatin 1.5 mg/kg). Rats in the group 3 (MEL group) received 10 mg/kg/day melatonin once daily. Group 4 received the melatonin (30 min before the BEP injections) and BEP as in groups 2. Proliferating cell nuclear antigen (PCNA) staining was used to detect cell proliferation and caspase-3, caspase-9 and Caspase-8 were detected to investigate apoptosis. PCNA immunostaining in alveolar epithelium, alveolar macrophages and bronchus was weak to moderate in BEP group. However, diffuse and strong caspase immunoreactions for caspase-3, caspase 8- and caspase-9 were detected in the bronchioles epithelium, vascular endothelium, alveolar luminal macrophages in the BEP group. PCNA and caspase immunoreactivities in MEL and Mel + BEP groups were close to the control one. The surface are in the BEP group was significantly reduced as compared to the control one ((P<0.05). However, in MEL and Mel + BEP groups, it was close to the control value (P>0.05). It can be concluded that BEP regimen can affects negatively on lung tissue and melatonin inhibits lung tissue injuries during BEP chemotherapy.

Photoperiodic-dependent histomorphological changes in the excurrent duct system of helmeted guinea fowl subjected to short day (8L:16D), long-day (16L:8D) light/dark cycles and exogenous melatonin

In the present study, the influence of varying photoperiods [short day light 8L:16D, long day light 16L;8D] and exogeneous melatonin on the excurrent duct system of male helmeted guinea fowl was investigated using histo-morphological and histometric approaches. A total of twenty-eight (28) guinea fowl birds were randomly divided into Group I: Short daylight (SD; 8 HL), Group II: (SD +1mg/kg melatonin; 8 HL+ Mel), Group III: Long daylight (LD; 16 HL) and Group IV: (LD +1mg/kg; 16 HL + Mel)] and comprises of seven birds (n=7) per group. At the end of the 8 weeks of experimentation, the excurrent ducts were excised and processed for routine histological examination and the variations in histo-morphometrical parameters were determined using the GIMP2 software. Histologically, apart from the moderate cellular degeneration observed in efferent duct epithelia of the SD subgroups: (8 HL and 8 HL + Mel), there was remarkable spermatozoa presence in the lumens of the epididymal duct and ductus deferens of both 16 HL and 16 HL + Mel groups. The histo-morphometric data (luminal, ductal diameters and epithelial heights) were significantly increased (p <0.05) in the excurrent ducts of guinea fowl exposed to 16 HL and 16 HL + Mel, as compared to other groups. There was significant decrease (p <0.05) in stereocilia height (SH) in 16 HL compared to 8 HL sub-groups of lower segments. Although, a non-significant (p >0.05) increase in SH was observed in melatonin-treated groups, regardless of photoperiod. Taken together, these sets of data from this study indicate the importance of artificial light and exogenous melatonin in the control of seasonality of reproduction and which could be used to influence the reproductive cycle of the guinea fowl.

The role of selenoprotein M in nickel-induced pyroptosis in mice spleen tissue via oxidative stress.

Nickel (Ni) is a heavy metal element and a pollutant that threatens the organism's health. Melatonin (Mel) is an antioxidant substance that can be secreted by the organism and has a protective effect against heavy metals. Selenoprotein M (SelM) is a selenoprotein widely distributed of the body, and its role is to protect these tissues from oxidative damage. To study the mechanism of Ni, Mel, and SelM in mouse spleen, 80 SelM+/+ wild-type and 80 SelM-/- homozygous mice were divided into 8 groups with 20 mice in each group. The Ni group was intragastric at a concentration of 10mg/kg, while the Mel group was intragastric at 2mg/kg. Mice were injected with 0.1mL/10g body weight for 21days. Histopathological and ultrastructural observations showed the changes in Ni, such as the destruction of white and red pulp and the appearance of pyroptosomes. SelM knockout showed more severe injury, while Mel could effectively interfere with Ni-induced spleen toxicity. The results of antioxidant capacity determination showed that Ni could cause oxidative stress in the spleen, and Mel could also effectively reduce oxidative stress. Finally, Ni exposure increased the expression levels of the pyroptotic genes, including apoptosis-associated speck protein (ASC), absent in melanoma-2 (AIM2), NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), Caspase-1, interleukin- (IL-) 18, and IL-1β (p < 0.05). Loss of SelM significantly increased these (p < 0.05), while Mel decreased the alleviated impact of Ni. In conclusion, the loss of SelM aggravated Ni-induced pyroptosis of the spleen via activating oxidative stress, which was alleviated by Mel, but the effect of Mel was not obvious in the absence of SelM, which reflected the important role of SelM in Ni-induced pyroptosis.

Decreased thioredoxin reductase 3 expression promotes nickel-induced damage to cardiac tissue via activating oxidative stress-induced apoptosis and inflammation.

Thioredoxin reductase 3 (Txnrd3) plays a crucial role in antioxidant and anti-cancer activities, and sperm maturation. The damage of heavy metals, including Nickel (Ni), is the most prominent harm in social development, and hampering Txnrd3 might exacerbate Ni-induced cardiac damage. In this study, a total of 160 8-week-old C57BL/N male mice with 25-30 g weight of Txnrd3+/+ wild-type and Txnrd3-/- homozygote-type were randomly divided into eight groups. The mice in the control and Ni groups were gavaged with distilled water and a freshly prepared 10mg/kg NiCl2 solution. Melatonin (Mel) groups were administered at a concentration of 2mg/kg for 21 days at the mice's 0.1ml/10g body weight. Ni exposure up-regulated the messenger RNA (mRNA) levels of mitochondrial apoptosis (caspase-3, caspase-9, cytochrome c, p53, and BAX), autophagy (LC3, ATG 1, ATG 7, and Beclin-1), and inflammation (TNF-α, COX 2, IL-1β, IL-2, IL-6, and IL-7)-related markers, but down-regulated the mRNA levels of BCL-2, p62 and mTOR (p < .05). Ni exposure decreased the expression of BCL-2 and p62 protein but increased the expression levels of caspase-3, caspase-9, cytochrome c, p53, BAX, ATG 7, Beclin-1, TNF-α, COX 2, IL-1β and IL-2 protein (p < .05). Ni increased the contents of glutathione disulfide (GSSG) and malondialdehyde (MDA) and decreased the activities of catalase (CAT) and total superoxide dismutase (T-SOD) (p < .05). Decreased Txnrd3 expression significantly exacerbated changes compared to the Ni exposure (p < .05). Mel significantly attenuated these changes, but the effect decreased when Txnrd3 was inhibited (p < .05). In conclusion, decreased Txnrd3 expression promoted Ni-induced mitochondrial apoptosis and inflammation via oxidative stress and aggravated heart damage in mice. Decreased Txnrd3 expression significantly reduced the protective effect of Mel to Ni exposure.

Single melatonin injection enhances the testicular artery hemodynamic, reproductive hormones, and semen parameters in German shepherd dogs

This study aimed to determine the effects of melatonin administration on testicular vascular perfusion in relation to steroid hormones and semen characteristics in dogs. The study included 12 normospermic German shepherd dogs (weighed 35 ± 0.5 kg and aged 4 ± 0.5 years). Males received a single melatonin administration (melatonin dimethyl sulfoxide + corn oil via subcutaneous route; MEL; n = 6), while the rest of the animals served as controls (dimethyl sulfoxide + corn oil; Control; n = 6). Males were subjected to routine examination on days -15, 0, 15, 30, 45, and 60. All examined dogs were subjected to Doppler screening, semen collection, and blood sampling. The MEL group showed a significant (P < 0.05) elevation in semen volume, concentration, percentage of sperm motility, and total sperm × 106 / ejaculate compared to other control males. Doppler indices as resistance (RI) and pulsatility (PI) indices declined (P < 0.05) from D 30 (1.02 ± 0.01) until day 60 (0.87 ± 0.02) of treatment. In MEL males, the peak systolic point of velocity (PSV; cm/sec) of the testicular artery elevated (P < 0.05) on day 60 (20.15 ± 0.99) compared to its value on day 0 (17.39 ± 1.84). On D 60, the levels of testosterone (T), estradiol 17-ß (E2), and nitric oxide (NO) elevated (P < 0.05). A negative correlation was detected between testicular volume, scrotal circumference (SC), T levels, Doppler indices, and velocities. In conclusion, single melatonin administration could improve testicular vascularization via increasing Doppler velocities and intratesticular colored areas. In addition, it could improve semen picture and steroids (T and E2) and nitric oxide.

Therapeutic Effect of Bee Venom and Melittin on Skin Infection Caused by Streptococcus pyogenes.

Streptococcus pyogenes (S. pyogenes) bacteria cause almost all primary skin infections in humans. Bee venom (BV) and melittin (Mel) have multiple effects, including antibacterial and anti-inflammatory activities. This study aims to demonstrate their effects on bacterial mouse skin infection using S. pyogenes. The dorsal skin was tape-stripped, then S. pyogenes was topically applied. BV or Mel were topically applied to the lesion. The tissues were stained with hematoxylin and eosin, while immunohistochemical staining was performed with anti-neutrophil. S. pyogenes-infected skin revealed increased epidermal and dermal layers, but it was reduced in the BV and Mel groups. Finding increased neutrophils in the mice infected with S. pyogenes, but the BV and Mel mice showed decreased expression. These results suggest that BV and Mel treatments could reduce the inflammatory reactions and help improve lesions induced by S. pyogenes skin infection. This study provides additional assessment of the potential therapeutic effects of BV and Mel in managing skin infection caused by S. pyogenes, further suggesting that it could be a candidate for developing novel treatment alternative for streptococcal skin infections.

PSXIII-B-19 The Effect of Maternal Melatonin Supplementation During mid to Late Gestation on Fetal Piglet Hepatic Gene Expression

Abstract Using melatonin as a gestational therapeutic due to its antioxidant and vasodilative properties increases fetal morphometric measurements in ruminant models, however its effects on gestating swine and fetal circadian regulation remain unknown. This study evaluated the effects of dietary melatonin supplementation during gestation on fetal hepatic circadian regulatory and metabolic gene expression. Twenty-four pregnant sows were randomly assigned to either melatonin (20mg/d; MEL) or control (CON) and 0500h (AM) or 1700h (PM) harvest timepoint across fall and spring replicates. The fall replicate occurred from gestational day 38±1 to 99±1, while spring was days 41 to 106±1. At harvest small, medium, and large piglets were identified by body weight and their livers were collected. Data were analyzed using a linear mixed model by the MIXED procedure of SAS. Cry1 expression tended to increase (P=0.0575) in large fetuses compared to small during the fall, while large fetuses had the greatest expression, medium intermediary, and small least during the spring (P=0.0056). Cry2 was reduced (P&amp;lt; 0.001) in MEL offspring compared to CON in the fall. There was a Treatment × Class interaction (P=0.0104) for Cry2 expression during spring wherein, CON-AM was reduced compared to CON-PM, however no differences between MEL groups. A Treatment × Class interaction (P=0.0511) of Per2 expression was present in the fall, where expression of small control fetuses was reduced compared to remaining controls. Spring Per2 expression increased (P=0.0122) in large fetuses compared to other sizes, Per2 also increased (P=0.0039) in PM compared to AM. Fall IGF1 expression increased (P=0.0366) in large fetuses compared to medium and small, and spring IGF1 expression increased (P=0.0067) in large fetuses compared to small. These findings suggest that maternal melatonin supplementation during gestation modulates expression of hepatic circadian regulatory and metabolic genes which may impact growth and developmental efficiency postnatally in a seasonal manner.

PSI-16 Effects of Melatonin on Physiological Parameters, Chute and Exit Scores in Beef Calves Exposed to Summer Heat Stress

Abstract This study was designed to evaluate the effects of melatonin on rectal temperature (RT), respiratory rate (RR), heat shock protein 70 (HSP 70), growth hormone (GH), chute (CS) and exit scores (ES) in beef calves exposed to heat stress during the summer. A total of twenty (20) eight months old calves divided into 2 groups were used for the study: melatonin group (MEL, n = 10) received 24mg of melatonin, once every 28 days, and control group (CON, n = 10) did not receive any subcutaneous melatonin implant. The effect of melatonin on RT, RR, HSP 70, GH, chute (CS) and ES were evaluated biweekly (Day 0, 14, 28, 42, 56, 70). The mean ambient temperature (AT) 24.00 ± 0.21°C, relative humidity (RH) 81.60 ± 0.76 % and temperature-humidity index (THI) 89.97 ± 0.70 recorded during the study were above the normal range reported for calves. The biweekly fluctuation of weight gain (WG) in MEL were higher than the CON. The mean RT (39.40 ± 0.06°C), RR (62.57 ± 1.15 cpm), CS (1.13 ± 0.04) and ES (1.5 ± 0.09) in the MEL group were lower (P &amp;lt; 0.05) than the corresponding values of 40.10 ± 0.06°C, 71.53 ± 1.59 cpm, 1.40 ± 0.07 and 1.80 ± 0.10 in the CON group. The biweekly variations in RT, RR, CS, ES, HSP 70 were lower (P &amp;lt; 0.05) in the MEL than the CON. Growth hormone concentrations were higher at D56 and 70 in MEL compared to the CON. Our results demonstrated that MEL ameliorates heat stress during the summer by lowering RT, RR, CS, and ES of beef heifers during the study period. In addition, melatonin influenced the biweekly variation in WG, RT, RR, CS, ES, HSP 70 and GH of heifers during the study period.

ADSCs Combined with Melatonin Promote Peripheral Nerve Regeneration through Autophagy.

Background In the early stage of nerve injury, damaged tissue is cleared by autophagy. ADSCs can promote nerve axon regeneration. However, the microenvironment of the injury was changed, and ADSCs are easily apoptotic after transplantation. Mel plays a role in the apoptosis, proliferation, and differentiation of ADSCs. Therefore, we investigated whether Mel combined with ADSCs promoted peripheral nerve regeneration by enhancing early autophagy of injured nerves. Materials and Methods SD rats were randomly split into the control group, model group, Mel group, ADSCs group, ADSCs + Mel group, and 3-MA group. On day 7, autophagy was observed and gait was detected on days 7, 14, 21, and 28. On the 28th day, the sciatic nerve of rats' renewal was detected. Results After 1 w, compare with the model group, the number of autophagosomes and lysosomes and the expressions of protein of LC3-II/LC3-I and Beclin-1 in the ADSCs + Mel group were prominently increased, while the 3-MA group was significantly decreased. After 4 w, the function of the sciatic nerve in ADSCs + Mel was similar to that in the control group. Compared with the model group, the ADSCs + Mel group significantly increased myelin regeneration and the number of motor neurons and reduced gastrocnemius atrophy. Conclusions It was confirmed that ADSCs combined with Mel could promote sciatic nerve regeneration in rats by changing the early autophagy activity of the injured sciatic nerve.

EXPOSURE TO MELAMINE FROM THE EARLY POSTNATAL PERIOD CAUSES NEPROTOXICITY: A HISTOPATHOLOGIC AND ULTRASTRUCTURAL STUDY

Objective: Melamine (mel), which is illegally added to formula to providing false-positive protein content, has caused acute renal failure in infants due to crystal formation. This study aimed to investigate the nephrotoxic effects of chronic low-dose mel exposure from the weaning period (supplementary food period). Materials and Methods: Eighteen female rats in the weaning period (21-days-old) were divided into three groups. A 0.1 ml saline was given to the control group by oral gavage (p.o). Fifty mg/kg mel was given to the second group and 75 mg/kg mel to the third group dissolved in 0.1 ml saline for twenty one days p.o.. At the end of the experiment, the animals were sacrificed, and histopathologic, morphometric, and ultrastructural analysis were performed on kidney tissues. Results: There was an inflammatory cell infiltration in the tubulointerstitial area, and no crystal formation was observed in either of the mel groups. In the 75 mg mel group, glomerular and tubular epithelial damage and significant increases in Bowman’s space were observed (p&lt;0.05). In the ultrastructural analysis, the capillary lumen was closed due to endothelial enlargement, dilatation in the pedicles and hypertrophy in podocytes were found in the 75 mg group. Pedicles in the 50 mg group appeared to be enlarged more than the control group, but the capillary lumen was more open than the 75 mg group. Conclusion: The results show that low dose mel exposure causes kidney damage with increased doses from the early postnatal period.

Effects of EGF and melatonin on gene expression of cumulus cells and further in vitro embryo development in bovines.

Despite previous research demonstrating the benefits of including growth factors and antioxidants to maturation medium to support embryo production, to date the effect of epidermal growth factor (EGF) and melatonin (Mel) on oocyte competency has not been studied. This study supplemented in vitro maturation (IVM) medium with EGF (10 ng/ml) and Mel (50 ng/ml) alone, or in combination, and evaluated cumulus cell (CC) gene expression and the development and quality of parthenogenetic blastocysts. No differences in CC gene expression levels indicative of developmental potential were found among the treatment groups. Antioxidant gene CuZnSOD was significantly (P < 0.05) decreased in CCs from the Mel group. Moreover, blastocyst rates on day 7 were significantly increased in EGF or Mel (P < 0.05), but not EGF+Mel. Significant decrease (P < 0.05) in GPX1, CuZnSOD, SLC2A1 and HSPA1A (P = 0.07) mRNA levels was observed in blastocysts from the Mel group. OCT4 gene expression was significantly increased (P < 0.05) in EGF+Mel and confirmed using immunofluorescence. Our results indicate that, despite the lack of changes of competence-related genes in CCs, IVM medium supplemented with Mel improved the culture environment sufficiently, resulting in improved blastocysts. Moreover, EGF and Mel combined during maturation increased OCT4 gene and protein expression in blastocysts, indicating its potential for stem cells.

Melatonin improves testicular hemodynamics and sperm quality in rams subjected to mild testicular heat stress

Melatonin is a potent free-radical scavenger, with anti-inflammatory, anti-oxidative, and anti-apoptotic effects. The objective was to determine whether melatonin promoted testicular blood flow and protected sperm quality in rams after mild heat stress (HS; scrotal neck insulation). Twelve yearling Dorset rams with good semen quality were housed indoors (∼18–20 °C). Once weekly for 2 wk, Doppler indices (resistive index [RI] and pulsatility index [PI]) were measured in the supratesticular artery and semen collected by electroejaculation. Then, rams were randomly allocated into two equal groups, and given either 36 mg melatonin in 1 ml corn oil SQ under the ear (MEL), or only corn oil (CONT). At 15 d after treatment, all rams were subjected to mild HS for 96 h, with blood flow measurements and semen collection done once weekly for 7 wk. There were group, week and group∗week interaction effects (P < 0.005) for total and progressive sperm motility (CASA); total sperm abnormalities and acrosome integrity had effects of group, week and group∗week interaction effects (P < 0.00); and there were group and week effects for RI and PI (P < 0.005), with no significant differences before treatment. Changes in total and progressive motility and sperm abnormalities were evident at Week 1 post-HS in CONT rams, but MEL mitigated (P ˂ 0.05) these effects from Weeks 2–7. Furthermore, both PI and RI were reduced (P ˂ 0.05; i.e., significant increase in blood flow) in MEL versus CONT rams most weeks after HS. In MEL rams, sperm motility and total abnormalities had recovered at Weeks 5 and 6, respectively, whereas CONT rams had not completely recovered by Week 7. There was no difference (P < 0.05) between MEL and CONT groups in scrotal subcutaneous temperatures in the 4-d intervals before, during and after HS. In conclusion, melatonin significantly improved testicular blood flow and protected sperm motility and morphology in rams exposed to testicular HS. Therefore, melatonin has potential for mitigating effects of testicular HS under field conditions.

Melatonin relieves liver fibrosis induced by Txnrd3 knockdown and nickel exposure via IRE1/NF-kB/NLRP3 and PERK/TGF-β1 axis activation

AimsNickel(Ni) accumulates in the environment due to human activities such as electroplating, alloy production, stainless steel, Ni‑cadmium batteries and industrial production. Ni enriched in humans and animals through food chains, poses a serious health threat. Txnrd3, as a member of the thioredoxin reductase family, has long been thought to be testicular specific and involved in sperm maturation. However, its role in liver diseases still unknown. Melatonin exerts its antioxidant effects directly through its ability to clear free radicals and protects the liver from oxidative damage. Hepatic fibrosis with an ever-increasing incidence year by year, is correlating with outcome and risk of hepatocellular carcinoma. Materials and methodsIn this study, 60 8-week-old male C57BL/6 wild-type mice and 60 Txnrd3−/− mice were randomly divided into three groups, respectively. Control group was gavaged with distilled water, 10 mg/kg NiCl2 in Ni group, Ni + Mel group treated with 2 mg/kg melatonin in the morning, 10 mg/kg NiCl2 in the afternoon, serum and tissue was extracted after 21 days. Key findingsResults showed that liver function was significantly worse after Ni exposure, morphological and masson staining showed more significant liver fibrosis in Txnrd3−/− mice, damage of organelles in hepatocytes was observed. qPCR and WB results showed activation of the IRE1/Nuclear factor-kappa B/NLRP3 axis during Ni exposure lead to hepatocyte pyroptosis, while upregulation of PERK/TGF-β promoted liver fibrosis process and Txnrd3 knockout exacerbated liver damage during Ni exposure. SignificanceThe above results will lay the theoretical foundation for the monitoring and clinical treatment of Ni exposure.

Melatonin is effective in attenuating cisplatin-induced neurotoxicity.

Cisplatin (Cis) is a chemotherapeutic agent that has many side effects. Neurotoxicity is one of the most important of these side effects. Oxidative stress and neuroinflammation are the best-known mechanisms in the pathogenesis of neurotoxicity development. In this study, we aimed to determine whether melatonin (Mel), with antioxidant and anti-inflammatory effects, is effective in preventing Cis-induced neurotoxicity. Forty-eight male Sprague-Dawley rats were divided into six groups (n = 8) as follows: control (0.9% NaCl), vehicle (5% ethanol), Cis (6 mg/kg), Cis (6 mg/kg) + vehicle (5% ethanol), Mel (20 mg/kg), and Cis (6 mg/kg) + Mel (20 mg/kg) groups. Cis was administered as a single dose on the 3rd day of the experiment while Mel was given for 5 days. All administrations were performed via intraperitoneal injection. After injections, T-maze, rotarod, and hot plate tests were performed to evaluate cognitive, motor, and sensory functions, respectively. Following sacrification oxidative stress markers, cholinergic function, and proinflammatory cytokines were studied from brain homogenates. Cis impaired cognitive function and motor performance in the Cis and Cis+Vehicle groups. The drug also increased oxidative stress in the brain. Mel significantly improved brain oxidant/antioxidant status and also decreased the overproduction of proinflammatory cytokines (superoxide dismutase activities in Cis+Vehicle and Cis+Mel groups: 104.55 ± 9.50 µU/mg protein vs. 150.13 ± 4.70 µU/mg protein, respectively, p < 0.05; tumor necrosis factor-α levels in Cis and Cis+Mel groups: 40 pg/ml vs. 20 pg/ml, respectively, p < 0.05). It seems that Mel can improve Cis neurotoxicity. For a more firm conclusion, further studies using Mel at different doses with larger groups should be performed.

Adding bendamustine to melphalan before ASCT improves CR rate in myeloma vs. melphalan alone: A randomized phase-2 trial

Definite cure remains exceptional in myeloma patients even after high-dose chemotherapy (HDCT) with melphalan (Mel) and autologous stem cell transplantation (ASCT). Thus, improving efficacy of HDCT in MM remains an unresolved issue. This randomized phase II trial compared standard 200 mg/m2 Mel HDCT to experimental HDCT with 200 mg/m2 bendamustine, given both at days −4 and −3, combined with 100 mg/m2 melphalan at days −2 and −1 (BenMel) before ASCT as first-line consolidation in myeloma patients. The primary endpoint aimed to identify at least a 15% improvement in the complete remission rate (stringent CR + CR) after HDCT with BenMel compared with Mel alone. A total of 120 MM patients were 1:1 randomized. The rate of sCR/CR after ASCT was higher in BenMel than in Mel treated patients (70.0% vs. 51.7%; p = 0.039). Three patients in the BenMel group (5.0%) had reversible acute renal insufficiency compared with none in Mel patients. Minimal residual disease negativity (<10-5) by flow cytometry was observed in 26 (45.6%) BenMel patients and 22 (37.9%) in the Mel group (p = 0.375). Our data suggest that BenMel HDCT is safe and improves the sCR/CR rate compared with standard Mel alone.

Comparison of lidocaine alone or in combination with a local nerve block of ethanol, bupivacaine liposome suspension, or oral meloxicam to extend analgesia after scoop dehorning in Holstein calves

The American Veterinary Medical Association recommends the use of practices that reduce or eliminate pain and discomfort associated with dehorning. Identification of an effective, long-acting local anesthetic that is practical for producers to implement and reduces pain from dehorning would benefit animal welfare. Thirty-two Holstein bulls and heifers were enrolled. The objective of this study was to compare the efficacy and duration of activity of bupivacaine liposome suspension (BUP; n = 8), ethanol (ETH; n = 8), or meloxicam (LID + MEL; n = 8) co-administered with lidocaine compared with lidocaine only (LID; n = 8), and to quantify their effect on pain biomarkers and behaviors after scoop dehorning with cauterization in approximately 20-wk-old calves. Outcome variables collected included infrared thermography (IRT), mechanical nociceptive threshold (MNT), visual analog scale (VAS) scoring, and blood sampling for serum cortisol and prostaglandin E2 metabolites (PGEM). There was evidence of a sex effect for MNT, with bulls demonstrating a higher threshold (13.74 kgf) compared with heifers (12.12 kgf). There was a treatment by time interaction for cortisol concentrations (ng/mL). At 2 h, the BUP group had higher cortisol values (17.32 ng/mL) than the LID + MEL group (3.10 ng/mL). Heifers also had higher mean cortisol values (13.88 ng/mL) compared with bulls (6.96 ng/mL). There was a treatment by time interaction for PGEM concentration. Calves in the LID + MEL group had lower PGEM values at 4 and 8 h (10.23 and 9.12 pg/mL) than at −24, 0, and 0.5 h (20.38, 27.27, and 22.59 pg/mL, respectively). At 4 h, the LID + MEL group had lower PGEM concentrations (10.23 pg/mL) than the ETH group (27.08 pg/mL). At 8 h, the LID + MEL group had lower PGEM concentrations (9.12 pg/mL) than both the ETH and BUP groups (24.80 and 20.52 pg/mL). Thus, LID + MEL reduced cortisol and prostaglandin metabolite concentrations more effectively than ETH + LID or BUP + LID administered as a local infiltration and cornual block, respectively, before scoop dehorning followed by cauterization. The treatments administered in the present study did not seem to extend the duration of analgesia beyond the currently recommended multimodal approach, including local anesthesia and systemic analgesia such as lidocaine and meloxicam. Evidence from the current study suggests that sex influences pain biomarkers such as nociceptive threshold and cortisol concentration, with males having a higher nociceptive threshold and lower cortisol responses.

Comparison between microendoscopic laminectomy and open posterior decompression surgery for single-level lumbar spinal stenosis: a multicenter retrospective cohort study

BackgroundMicroendoscopic laminectomy (MEL), in which a 16-mm tubular retractor with an internal scope is used, has shown excellent surgical results for patients with lumbar spinal canal stenosis. However, no reports have directly compared MEL with open laminectomy. This study aimed to elucidate patient-reported outcomes (PROs) and perioperative complications in patients undergoing MEL versus open laminectomy.MethodsThis is a multicenter retrospective cohort study of prospectively registered patients who underwent lumbar spinal surgery at one of the six high-volume spine centers between April 2017 and September 2018. A total of 258 patients who underwent single posterior lumbar decompression at L4/L5 were enrolled in the study. With regard to demographic data, we prospectively used chart sheets to evaluate the diagnosis, operative procedure, operation time, estimated blood loss, and complications. The follow-up period was 1-year. PROs included a numerical rating scale (NRS) for lower back pain and leg pain, the Oswestry Disability Index (ODI), EuroQol 5 Dimension (EQ-5D), and patient satisfaction with the treatment.ResultsOf the 258 patients enrolled, 252 (97%) completed the 1-year follow-up. Of the 252, 130 underwent MEL (MEL group) and 122 underwent open decompression (open group). The MEL group required a significantly shorter operating time and sustained lesser intraoperative blood loss compared with the open group. The MEL group showed shorter length of postoperative hospitalization than the open group. The overall complication rate was similar (8.2% in the MEL group versus 7.7% in the open group), and the revision rate did not significantly differ. As for PROs, both preoperative and postoperative values did not significantly differ between the two groups. However, the satisfaction rate was higher in the MEL group (74%) than in the open group (53%) (p = 0.02).ConclusionsMEL required a significantly shorter operating time and resulted in lesser intraoperative blood loss compared with laminectomy. Postoperative PROs and complication rates were not significantly different between the procedures, although MEL demonstrated a better satisfaction rate.

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.

Amelioration of Chemical Induced Hepatic Injury by Vitex agnus castus ExtractAmelioration of Chemical Induced Hepatic Injury by Vitex agnus castus Extract

Objective: The liver is the major organ of detoxification of ingested materials such as food, beverages and drugs, thus it is prone to toxicity with attendant pathologies. We studied the ability of Vitex agnus castus plant extract to ameliorate the biochemical and structural alterations in Wistar rats with carbon tetrachloride-induced liver injury.&#x0D; Methods: Forty adult male Wistar rats were allotted into eight equal groups. Group1 was normal control (NC); Group 2 Liver injury without extract (LI). The remaining six groups were paired composite group of varying dosage of the plant extract (200 mg/kg, 400 mg/kg and 600 mg/kg). Only one member of each pair had induced liver injury. Consequently, the groups were Low extract without liver injury (LE), Low extract with liver injury (LEL); Medium extract without liver injury(ME)&#x0D; Medium extract with liver injury (MEL) and High extract without liver injury (HE),High extract with liver injury (HEL).The biochemical parameters evaluated were the liver function test {Total protein plus globulin and albumen fractions; liver enzymes- alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase}. Oxidative stress was evaluated by measuring the activities of antioxidants namely; Superoxide dismutase (SOD), Catalase, Malondialdehyde (MDA) and Glutathione Peroxidase (GPx).Histology of the harvested liver specimens was used to assess the structural alterations.&#x0D; Results: The mean liver weight was highest in the HEL group and significantly different from that of its control (HE) and NC.The mean serum total protein of all the groups were significantly higher than that of the NC.The mean aspartate amino transferase levels of the LEL, ME and MEL groups were significantly lower than that of the control while that of the HEL was significantly higher than those of the LEL and MEL. The results of alanine amino transferase were similar to those of aspartate amino transferase. The alkaline phosphatase levels in all the experimental groups were significantly depressed when compared with the control. Amongst the experimental groups, the serum alkaline phosphatase level was significantly raised than those of the LEL, and MEL groups.&#x0D; The glutathione (GSH) activities of LE, HE and HEL were significantly lower. While the glutathione peroxidase (GPX) activity of the control was significantly lower to those of groups LEL, ME, MEL and HEL.Histopathology of the liver showed preservation of the liver architecture with normal hepatocytes in all the groups.&#x0D; Conclusion: The ethanolic extract of Vitex agnus castus was able to reduce the severity of carbon tetrachloride induced liver injury in wistar rats.