Equivalent Amount Of Normal Saline Research Articles

Antinociceptive Evaluation of Antidepressants (Cita- lopram, Duloxetine and Amitriptyline) in a Mouse Model of Acute Pain

Introduction: Acute pain is a pervasive and debilitating symptom affecting the general population as well as depressed patients who suffer even more from pain and fatigue. Aims and Objectives: To evaluate the antinociceptive effect induced by antidepressants (Citalopram, Duloxetine and Amitriptyline) in acute pain induced in mice. Place and Duration of study: Animal Research Laboratory of University of Lahore. Study Period: 2018- 2019 Material and Methods: An experimental animal study was carried out on 25 albino mice. The mice were divided into 5 groups; Group 1: Positive Control (PC), Group 2: Ibuprofen (IBO) (Standard) 80mg/kg, Group3: Citalopram (CTP)3mg/kg, Group 4: Duloxetine (DXT) 25mg/kg, Group 5: Amitriptyline (AMT) 15mg/kg. Groups 2-5 were administered drugs orally through a feeding tube as per group designation while Group 1: Control was given an equivalent amount of normal saline. One hour post treatment with test drugs, all Groups (1-5) were injected 10 ml/ kg of 2% acetic acid I/P and number of writhing movements consisting of contraction of abdominal muscles leading to extension of hind limb and periodic arching of body as well as paw licking behavior were counted for 20 minutes at 5- minute interval, using hand tally counter. Degree of analgesia was calculated by using formula of percentage effectiveness. Data was entered and analyzed utilizing SPSS version 21, p?0.05 was taken as significant. Results: Ibuprofen completely eliminated the nociceptive outcome of diluted acetic acid in writhing and licking of experimental animals. Citalopram, showed maximum decreasing effect (95%-96%) in writhing in 5-20 min. However, its effect in paw licking was low. Duloxetine showed 70% to 90% decrease in writhing at 5-20 min whereas 100 % inhibition of paw-licking was observed at 5 to 20 minutes. The writhing effect of amitriptyline was 77%-90% at 5-20 min and paw licking effect was 80-90 % at 5-20 min. Conclusion: Amitriptyline, duloxetine and citalopram have significant effect in reducing the acute nociceptive pain and may be utilized as analgesic in acute state of pain.

Effects of Dexmedetomidine on Cognitive Function, Oxidative Stress and Brain Protection in Patients Undergoing Craniocerebral Surgery

Background: The protective mechanism of dexmedetomidine on the brains of patients undergoing craniocerebral surgery remains unclear. The aim of this study was to examine the impact of dexmedetomidine on cognitive function, oxidative stress, and brain protection in such patients. Methods: Fifty-four patients who underwent craniocerebral surgery at our hospital from January 2020 to June 2023 were retrospectively selected as study subjects. They were divided into two groups: the control group (n = 27) and the study group (n = 27), based on different auxiliary anesthesia protocols. Patients in the study group received dexmedetomidine before anesthesia induction, using a midline intravenous pump to assist anesthesia, while the control group received an equivalent amount of normal saline. The remaining anesthesia induction and maintenance protocols were consistent for both groups. Cognitive function was assessed using the Mini Mental State Examination (MMSE) before and 1 day after surgery for both groups. Oxidative stress indicators, including malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) levels in the serum of both groups, were measured using enzyme-linked immunosorbent assay (ELISA). Additionally, changes in postoperative brain injury indicators, namely neuron-specific enolase (NSE) and central nervous system-specific protein (S100β), were detected and compared in the serum of both groups. Concurrently, postoperative adverse reactions were recorded for both groups. Results: The MMSE scale scores of both groups of patients 24 hours after surgery were significantly lower than those before surgery. However, the MMSE scale scores of the study group patients were notably higher than those in the control group, with a statistically significant difference (p < 0.05). One hour after surgery, the serum levels of MDA, GSH-Px, and SOD in both groups of patients were significantly elevated compared to pre-surgery levels. Yet, the study group exhibited significantly lower levels of MDA, GSH-Px, and SOD in comparison to the control group, and these differences were statistically significant (p < 0.05). The serum levels of NSE and S100β in both groups were markedly higher than preoperative levels 24 hours after surgery. However, the study group demonstrated significantly lower levels of serum NSE and S100β compared to the control group, with a statistically significant difference (p < 0.05). The incidence of postoperative complications in the study group was 7.41% (2/27), indicating a decreasing trend compared to 18.52% (5/27) in the control group. However, this difference did not reach statistical significance (χ2 = 1.477, p = 0.224). Conclusion: Dexmedetomidine-assisted anesthesia in craniocerebral surgery can effectively enhance postoperative cognitive function, mitigate oxidative stress, and facilitate overall postoperative recovery for patients. The intervention exhibits a favorable safety profile with no reported serious adverse reactions, establishing it as a relatively safe and reliable approach.

Xinmaikang-mediated mitophagy attenuates atherosclerosis via the PINK1/Parkin signaling pathway

BackgroundThe Chinese herbal compound Xinmaikang (XMK) is effective in treating atherosclerosis (AS), although the associated mechanisms of action remain unclear. We hypothesize that XMK increases mitophagy via the PINK1/Parkin signaling pathway and decreases reactive oxygen species (ROS), thus treating AS. PurposeTo explore the above-mentioned mechanisms of action of XMK in AS. Materials and methodsUltra-performance liquid chromatography assay was performed to clarify the composition of XMK. A 16-week high-fat diet was fed to APOE−/− mice to form an AS model. Next, mice were given XMK(0.95 g/kg/d, 1.99 g/kg/d, 3.98 g/kg/d, i.g.) or Atorvastatin(3 mg/kg/d, i.g.) or Rapamycin(4 mg/kg/d, i.p.) or XMK with Mdivi-1(40 mg/kg/d, i.p.) or an equivalent amount of normal saline for 4 weeks. Then mice were examined for AS plaque area, lesion area, collagen fiber, pro-inflammatory cytokines, lipid level, ROS level and mitophagy level. We assessed AS using Oil Red O, hematoxylin and eosin, and Sirius red staining, as well as ROS measurements. Mitophagy was evaluated by transmission electron microscopy, real-time quantitative polymerase chain reaction (RT-qPCR), Western blot, single-cell Western blot, and immunofluorescence staining. In vitro, by oxidizing low-density lipoprotein, formation of RAW264.7 macrophage-derived foam cells induced. we induced foam cell formation in RAW264.7 macrophages. Then cells were incubated with XMK-medicated serum with or without Mdivi-1. We examined foam cell formation, ROS level, mitophagy level in cells. Finally, we knocked down the PINK1, and examined foam cell formation and PINK1/Parkin level in RAW264.7 macrophages. ResultsUPLC analysis revealed 102 main ingredients in XMK. In vivo, XMK at medium-dose or high-dose significantly reduced AS plaques, lipids, pro-inflammatory cytokines, and ROS and increased mitophagy. In further study, Single-cell western blot showed that mitophagy level in macrophages sorted from AS mice was lower than the control mice. While XMK improved mitophagy level. In vitro, XMK reduced foam cell formation and ROS and increased mitophagy. When PINK1 was knocked down, XMK's effects on foam cell formation and PINK1/Parkin pathway activation were reduced. ConclusionThe study shows that XMK is effective against AS by mediating macrophage mitophagy via the PINK1/Parkin signaling pathway. For the treatment of AS and drug discovery, it provides an experimental basis and target.

Curcumin alleviates nuclear factor-κB/NOD-like receptor protein 3 mediated renal injury caused by acute respiratory distress syndrome through reducing mitochondrial oxidative stress

To evaluate the effect of curcumin on renal mitochondrial oxidative stress, nuclear factor-κB/NOD-like receptor protein 3 (NF-κB/NLRP3) inflammatory body signaling pathway and tissue cell injury in rats with acute respiratory distress syndrome (ARDS). A total of 24 specific pathogen free (SPF)-grade healthy male Sprague-Dawley (SD) rats were randomly divided into control group, ARDS model group, and low-dose and high-dose curcumin groups, with 6 rats in each group. The ARDS rat model was reproduced by intratracheal administration of lipopolysaccharide (LPS) at 4 mg/kg via aerosol inhalation. The control group was given 2 mL/kg of normal saline. The low-dose and high-dose curcumin groups were administered 100 mg/kg or 200 mg/kg curcumin by gavage 24 hours after model reproduction, once a day. The control group and ARDS model group were given an equivalent amount of normal saline. After 7 days, blood samples were collected from the inferior vena cava, and the levels of neutrophil gelatinase-associated lipocalin (NGAL) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The rats were sacrificed, and kidney tissues were collected. Reactive oxygen species (ROS) levels were determined by ELISA, superoxide dismutase (SOD) activity was detected using the xanthine oxidase method, and malondialdehyde (MDA) levels were determined by colorimetric method. The protein expressions of hypoxia-inducible factor-1α (HIF-1α), caspase-3, NF-κB p65, and Toll-like receptor 4 (TLR4) were detected by Western blotting. The mRNA expressions of HIF-1α, NLRP3, and interleukin-1β (IL-1β) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Renal cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). The morphological changes in renal tubular epithelial cells and mitochondria were observed under a transmission electron microscope. Compared with the control group, the ARDS model group exhibited kidney oxidative stress and inflammatory response, significantly elevated serum levels of kidney injury biomarker NGAL, activated NF-κB/NLRP3 inflammasome signaling pathway, increased kidney tissue cell apoptosis rate, and renal tubular epithelial cell damage and mitochondrial integrity destruction under transmission electron microscopy, indicating successful induction of kidney injury. Following curcumin intervention, the injury to renal tubular epithelial cells and mitochondria in the rats was significantly mitigated, along with a noticeable reduction in oxidative stress, inhibition of the NF-κB/NLRP3 inflammasome signaling pathway, and a significant decrease in kidney tissue cell apoptosis rate, demonstrating a certain dose-dependency. Compared with the ARDS model group, the high-dose curcumin group exhibited significantly reduced serum NGAL levels and kidney tissue MDA and ROS levels [NGAL (μg/L): 13.8±1.7 vs. 29.6±2.7, MDA (nmol/g): 115±18 vs. 300±47, ROS (kU/L): 75±19 vs. 260±15, all P < 0.05], significantly down-regulated protein expressions of HIF-1α, caspase-3, NF-κB p65, and TLR4 in the kidney tissue [HIF-1α protein (HIF-1α/β-actin): 0.515±0.064 vs. 0.888±0.055, caspase-3 protein (caspase-3/β-actin): 0.549±0.105 vs. 0.958±0.054, NF-κB p65 protein (NF-κB p65/β-actin): 0.428±0.166 vs. 0.900±0.059, TLR4 protein (TLR4/β-actin): 0.683±0.048 vs. 1.093±0.097, all P < 0.05], and significantly down-regulated mRNA expressions of HIF-1α, NLRP3, and IL-1β [HIF-1α mRNA (2-ΔΔCt): 2.90±0.39 vs. 9.49±1.87, NLRP3 mRNA (2-ΔΔCt): 2.07±0.21 vs. 6.13±1.32, IL-1β mRNA (2-ΔΔCt): 1.43±0.24 vs. 3.95±0.51, all P < 0.05], and significantly decreased kidney tissue cell apoptosis rate [(4.36±0.92)% vs. (27.75±8.31)%, P < 0.05], and significantly increased SOD activity (kU/g: 648±34 vs. 430±47, P < 0.05). Curcumin can alleviate kidney injury in ARDS rats, and its mechanism may be related to the increasing in SOD activity, reduction of oxidative stress, and inhibition of the activation of the NF-κB/NLRP3 inflammasome signaling pathway.

A postpartum enriched environment rescues impaired cognition and oxidative markers in aged mice with gestational inflammation.

Previous studies have shown that gestational inflammation can accelerate age-associated cognitive decline (AACD) in maternal mice; enriched environments (EEs) have been reported to protect normally aging mice from AACD and improve mitochondrial function. However, it is unclear whether the nitrosative stress-related proteins tet methylcytosine dioxygenase 1 (TET1) and S-nitrosoglutathione reductase (GSNOR) are involved in the accelerated aging process of gestational inflammation and whether EEs can slow this process. In this study, CD-1 female mice on the 15th day of pregnancy were injected with bacterial lipopolysaccharide (50μg/kg; LPS group) or an equivalent amount of normal saline (CON group) from the abdominal cavity for 4 consecutive days. Twenty-one days after delivery, half of the LPS-treated mice were randomly selected for EE until the end of the behavioral experiment (LPS-E group). When the female rats were raised to 6 months and 18 months of age, the Morris water maze (MWM) was used to detect spatial learning and memory ability; RT-PCR and Western blots were used to measure the mRNA and protein levels of hippocampal TET1 and GSNOR. As for the control group, compared with 6-month-old mice, the spatial learning and memory ability of 18-month-old mice decreased, and the hippocampal TET1 and GSNOR mRNA and protein levels were decreased. Gestational inflammation exacerbated these age-related changes, but an EE alleviated the effects. Pearson's correlation analysis indicated that performance during the learning and memory periods in the MWM correlated with the levels of hippocampal TET1 and GSNOR. Our findings suggest that gestational inflammation accelerates age-related learning and memory impairments and that postpartum EE exposure could alleviate these changes. These effects may be related to hippocampal TET1 and GSNOR expression.

Protective effect of mitochondria-targeted antioxidant peptide SS-31 in sepsis-induced acute kidney injury

To study the effect and mechanism of mitochondria-targeted antioxidant peptide SS-31 on sepsis-induced acute kidney injury (AKI). Sixty adult male C57BL/6 mice were randomly divided into four groups according to the random number table method: sham group (10 mice), positive control group (10 mice), sepsis model group (20 mice), and SS-31 peptide group (20 mice). The sepsis-induced AKI mouse model was reproduced by cecal ligation and puncture (CLP). The sham group only received laparotomy. SS-31 peptide (5 mg/kg) was intraperitoneally injected in SS-31 peptide group and positive control group 30 minutes after the operation, while an equivalent amount of normal saline was given in sham group and sepsis model group for 7 days. The blood samples were collected 24 hours after the operation from orbit, and the serum was collected to test the serum creatinine (SCr) and blood urea nitrogen (BUN). The mice were sacrificed 7 days after surgery. The kidney tissues were collected to observe the pathologic structure changes under the hematoxylin-eosin (HE) staining by light microscope. And the mitochondrial ultrastructure was checked under the transmission electron microscope. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method (TUNEL). The expression level of peroxisome proliferator-activated receptorγ coactivator-1α (PGC-1α), adenosine monophosphate-activated protein kinase (AMPK), and cleaved caspase-3 protein were tested by Western blotting. Compared with sham group, the levels of SCr and BUN were significantly increased in sepsis model group [SCr (μmol/L): 93.12±11.80 vs. 32.94±3.37, BUN (mmol/L): 41.36±6.48 vs. 9.49±3.58, both P < 0.05]. The expression levels of AMPK, PGC-1α and cleaved caspase-3 protein increased (AMPK/β-actin: 0.30±0.02 vs. 0.12±0.01, PGC-1α/β-actin: 0.38±0.03 vs. 0.16±0.02, cleaved caspase-3/β-actin: 0.20±0.01 vs. 0.11±0.02, all P < 0.05). HE staining showed that inflammatory cell was infiltrated, glomerular basement membrane was exposed and vacuole-like transparent casts were found in the lumen. Mitochondria were damaged under electron microscope with swelling, ridge disappearance and ruptured membranes, with increasing of apoptotic cells [cells: 24.00 (18.75, 31.00) vs. 2.00 (0.72, 3.25), P < 0.05]. Meanwhile, compared with sepsis model group, the levels of SCr, BUN and the expressions of AMPK, PGC-1α, cleaved caspase-3 protein were significantly decreased in the SS-31 peptide group [SCr (μmol/L): 71.33±10.14 vs. 93.12±11.80, BUN (mmol/L): 27.00±5.52 vs. 41.36±6.48, AMPK/β-actin: 0.23±0.01 vs. 0.30±0.02, PGC-1α/β-actin: 0.27±0.02 vs. 0.38±0.03, cleaved caspase-3/β-actin: 0.13±0.01 vs. 0.20±0.01, all P < 0.05]. HE staining showed that cell swelling reduced, the mitochondrial structure was intact, the ridge swelling was also reduced, and the membrane structure was relatively intact, the number of apoptotic cells was significantly reduced [cells: 13.00 (9.00, 16.50) vs. 24.00 (18.75, 31.00), P < 0.05]. The protective effect of SS-31 peptide on organ dysfunction induced by sepsis-induced AKI is related to maintaining mitochondrial homeostasis and inhibiting cell apoptosis.

Preliminary study on cerebrospinal fluid proteomics of Erxian Decoction against neurogenesis impairment in late-onset depression

This study aims to elucidate the underlying mechanism of Erxian Decoction(EXD) against neurogenesis impairment in late-onset depression(LOD) rats based on cerebrospinal fluid(CSF) proteomics. A total of 66 20-21-month-old male Wistar rats were randomized into naturally aged(AGED) group, LOD group, and EXD group. All rats received chronic unpredictable mild stress(CUMS) for 6 weeks for LOD modeling except for the AGED group. During the modeling, EXD group was given EXD(ig, twice a day at 4 g·kg~(-1)) and other groups received equivalent amount of normal saline(ig). After modeling, a series of behavioral tests, such as sucrose preference test(SPT), open-field test(OFT), forced swimming test(FST), and Morris water maze test(MWMT) were performed. Immunofluorescence method was used to detect the number of Ki-67/Nesti-positive cells and BrdU/DCX-positive cells in the hippocampal DG area of each group. High-concentration corticosterone(CORT) was combined with D-galactose(D-gal) to simulate the changes of LOD-related stress and aging and the proliferation and differentiation of primary neural stem cells of hippocampus in each group were observed. Data independent acquisition(DIA)-mass spectrometry(MS) was used to analyze the differential proteins in CSF among groups and bioinformatics analysis was performed to explore the biological functions of the proteins. Behavioral tests showed that sucrose consumption in SPT, total traveling distance in OFT, and times of crossing the platform in MWMT were all reduced(P&lt;0.01) and the immobility time in FST was prolonged(P&lt;0.01) in the LOD group compared with those in the AGED group, suggesting that LOD rats had developed depression symptoms such as anhedonia, decreased locomotor activity ability, and cognitive dysfunction. Behavioral abnormalities were alleviated(P&lt;0.01, P&lt;0.05) in the EXD group as compared with those in the LOD group. Immunofluorescence results demonstrated that Ki-67/Nesti-positive cells and BrdU/DCX-positive cells in the hippocampal DG area were fewer(P&lt;0.05) in LOD group than in the AGED group, and the positive cells in the EXD group were more(P&lt;0.05) than those in the LOD group. In vitro experiment showed that the proliferation and differentiation of primary hippocampal neural stem cells under the CORT+D-gal treatment were reduced(P&lt;0.01). The proliferation rate of neural stem cells decreased(P&lt;0.05) in CORT+D-gal+LOD-CSF group but increased(P&lt;0.01) in CORT+D-gal+EXD-CSF group compared with that in the CORT+D-gal group. A total of 2 620 proteins were identified from rat CSF, with 135 differential proteins between the LOD group and AGED group and 176 between EXD group and LOD group. GDF11, NrCAM, NTRK2, and GhR were related to neurogenesis and 39 differential proteins were regulated by both LOD and EXD. EXD demonstrated obvious anti-LOD effect, as it improved the locomotor activity ability and cognitive function of LOD rats and protected the proliferation and differentiation of hippocampal neural stem cells. EXD exerts anti-LOD effect by regulating the proteins related to neurogenesis in CSF, such as GDF11, NrCAM, NTRK2, and GhR and maintaining hippocampal neurogenesis.

Impact of Topical Heparin on Healing of Skin Graft Donor Site in Burn Patients

Abstract Background The ability of topical heparin application to improve the healing outcome of burn wounds has been demonstrated by several studies. However, its impact on healing of skin graft donor site was not studied. Aim The present study was done to compare the healing outcome (healing time, pain, itching, scarring and complications) of topical heparin treatment with topical conventional treatment in the donor areas after skin grafting in burn patients. Methods This prospective, interventional, controlled, single-blinded clinical study was done on 40 patients with 2nd or 3rd degree burns of any etiology and &amp;lt;30% of body surface area requiring skin grafting, aged 18-65 years, of both sexes. Each patient was subjected to harvesting of two grafts. Patients served as their own controls. One donor area was treated with topical heparin and the other was treated with the topical conventional treatment. Immediately after graft harvesting, all donor areas were treated conventionally. Starting from the 2nd day, each donor area was treated once daily according to its group allocation. The topical heparin donor area was treated with heparin diluted in saline in a concentration of 250 IU/ml in a dose of 4200 IU/1% total body surface area (TBSA). The area was covered with gauze soaked with the solution for 5 days. The conventional treatment (control) donor area was covered by gauze soaked with an equivalent amount of normal saline on top of Vaseline gauze. Heparin was to be discontinued if the platelet count before each session was &amp;lt; 100,000 /mm3 and/or APTT exceeded double the reference value. Pain was assessed twice daily for 5 days. The patients’ donor areas were followed-up postoperatively for 8 weeks for healing time in days, itching over the wound and scarring using Vancouver Scar Scale. Complications in the form of wound site bleeding or infection were recorded. An analgesic was given twice daily for 5 days then as needed. Results There were no statistically significant differences between the two donor areas regarding the site and size. The healing time was significantly shorter in the heparin donor areas (P &amp;lt; 0.00001) with less scarring reported as significantly lower scores of the Vancouver scar scale compared with the control donor areas for each component and the total score (P &amp;lt; 0.05). Pain, itching and infection rate were insignificantly less in the heparin area. Bleeding was not observed in any of the areas in all cases and the daily values of platelet count and APTT in the five treatment days did not differ significantly compared with the preoperative values. None of the patients showed a platelet count &amp;lt; 100,000 /mm3 or APTT exceeding double the reference value. Conclusion Topical heparin treatment, compared with topical conventional treatment, of the donor areas after skin grafting in burn patients resulted in better clinical outcome manifested as significantly shorter wound healing time and significantly less scarring with no treatment-related complications.

Combined topical and intravenous administration of tranexamic acid further reduces postoperative blood loss in adolescent idiopathic scoliosis patients undergoing spinal fusion surgery: a randomized controlled trial

BackgroundTo indicate whether combined topical and intravenous (IV) administration of tranexamic acid (TXA) could further reduce the blood loss after surgery for adolescent idiopathic scoliosis (AIS) compared with IV-TXA alone.MethodsNinety AIS patients who underwent posterior spinal fusion were prospectively randomized to combined group (IV + topical- TXA group) and IV-TXA alone group. TXA was infused at a loading dose of 1 g from the beginning of the surgery with a maintenance dose of 10 mg/kg/h until the wound was closed. In the combined group, 2 g TXA was injected retrogradely through a drain, while an equivalent amount of normal saline was injected in the IV-TXA alone group. The drain tube was clamped for 2 h in both groups. The amount of wound drainage and transfusion rates were analyzed.ResultsThe drainage volume and duration of drain were significantly lower in the combined group compared with that in the IV-TXA alone group (372.0 ± 129.7 mL vs. 545.2 ± 207.7 mL, P < 0.001;64.7 ± 13.9 h vs. 82.0 ± 12.5 h, P < 0.001). Postoperative length of hospital stay was also significantly shorter in the combined group (6.5 ± 1.51 days vs. 7.95 ± 1.44 days, P < 0.05). Transfusion and complication rates were comparable between the two groups .ConclusionsIV injection of TXA combined with retrograde injection of TXA into a drain and clamping it for 2 h could further reduce the total volume of drainage in AIS patients who underwent spinal fusion surgery.Trial registrationChinese Clinical Trial Registry: ChiCTR1900024177, Registered 29 June 2019, http://www.chictr.org.cn/showproj.aspx?proj=40214

Effect of vasodilator PGE1 on sciatic nerve function, VEGF level, vascular permeability and peripheral nerve in type 2 diabetic rats

Purpose: To investigate the effect of vasodilator prostaglandin E1 (PGE1) on sciatic nerve function, vascular endothelial growth factor (VEGF), vascular permeability and peripheral nerve in type 2 diabetes mellitus (T2DM) rats.&#x0D; Methods: Twenty-one rats in the study group were intraperitoneally injected with PGE1, while rats in T2DM untreated group (n = 21) were injected with an equivalent amount of normal saline. Seven rats were randomly selected from the study and the control groups every seven days for 21 days for determination of changes in sciatic nerve function, VEGF level, vascular permeability and peripheral nerves.&#x0D; Results: Sciatic nerve motor nerve conduction velocity (MNCV) was significantly higher in the study group than in T2DM untreated control group at the three time-points post-treatment (p &lt; 0.01). The level of VEGF in the study group decreased, relative to the T2DM untreated control group on the 7th 14th and 21st days post- treatment (p &lt; 0.05) while the water content of sciatic nerve tissue in study group was markedly decreased, relative to control value on day 21 (p &lt; 0.05). Rats in the study group showed decreased TTT, relative to those in T2DM untreated group on days 7, 14 and 21 post-treatment (p &lt; 0.01).&#x0D; Conclusion: PGE1 improves the sciatic nerve function of T2DM rats, reduces the level of serum VEGF and vascular permeability, and protects peripheral nerves. These findings provide a basis for the development of new T2DM drugs

A Comparative Study of Intravenous Clonidine and Dexmedetomidine on Characteristics of Bupivacaine Spinal Anesthesia

Background: Spinal anesthesia with bupivacaine is administered routinely for lower abdominal and lower limb surgeries. The ensuing nerve block is sufficient to ensure patient’s well being, while motor block facilitates the surgeon’s work. In patients receiving spinal anaesthesia, with local anesthetic agents like bupivacaine, the addition of another drug as adjuvant prolongs the analgesia. The present study is designed to study the effect of dexmedetomidine (D) and Clonidine (C) on the duration of motor and sensory block as well as postoperative analgesia by intrathecal bupivacaine in patients undergoing lower limb orthopedic surgery. Subjects and Methods: This study was carried out on 90 patients in the age group of 18 to 50 years, belonging to the American Society of Anesthesiologists(ASA) physical status I and II presenting for lower limb orthopedic surgery were included in the study. Patients were divided randomly into 3 groups. Group D received 1μg kg-1of dexmedetomidine, group C received 2 μg kg-1 of clonidine and group NS Control group received an equivalent amount of normal saline. Results: From the current study we observed that single dose of 1 μg kg-1 dexmedetomidine over 20 minutes started 20 minutes after spinal block and a single dose of 2 μg kg-1 Clonidine resulted in a significant prolongation of time to two-segment regression, postoperative analgesia, sensory block and motor block with the maintenance of hemodynamic parameters. Intravenous dexmedetomidine was more effective than Clonidine at the prolongation of time to two-segment regression, postoperative analgesia, sensory block and motor block of spinal anesthesia with 0.5% hyperbaric bupivacaine. Conclusion: Dexmedetomidine (1μg kg-1) in comparison to Clonidine (2 μg kg-1) and placebo is far more effective in the motor blockade, sensory blockade and duration of postoperative analgesia.

Protective effects and mechanism of curcumin on myocardial injury induced by coronary microembolization.

Coronary microembolization (CME) is a common complication during the percutaneous coronary intervention (PCI). CME-induced local myocardial inflammation and myocardial apoptosis are the primary causes of progressive cardiac dysfunction. Curcumin exerts a protective role in various cardiovascular diseases; however, its effects in CME are yet to be clarified. Therefore, the current study investigated the effects of curcumin on myocardial inflammatory responses, myocardial apoptosis, and cardiac dysfunctions induced by CME in rats. A total of 40 Sprague-Dawley rats were randomly divided into the following groups: Sham operation (sham group),CME group, curcumin, and control with 10 rats in each group. The ascending aortas were clamped, and the CME-model group was established by injecting microspheres into the apex of the left ventricle. An equivalent amount of normal saline was injected to establish the sham group. The cardiac functions, serum c-troponin I level, and apoptotic index was examined. Also, the levels of Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MYD88), nuclear factor κB (NF-κB) p65, BCL2-associated Xprotein (Bax), B-cell lymphoma 2 (Bcl-2), cleaved caspase-3, tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β) were detected. Myocardial dysfunction enhanced serum c-troponin I, and apoptotic index were induced following CME. Moreover, CME elevated the expression of TLR4, MyD88, NF-κB p65, cleaved caspase-3, TNF-α, and IL-1β, while the Bcl-2/Bax ratio decreased. Curcumin reversed these effects by CME, while the gastric lavage control did not exert any effect. Curcumin was responsible for the anti-CME-induced myocardial injury. The effector mechanism might be related to the reduction of cardiomyocyte apoptosis and inhibition of myocardial inflammatory responses mediated by TLR4/MyD88/NF-κB signaling pathway.

Effects of atorvastatin on p38 phosphorylation and cardiac remodeling after myocardial infarction in rats.

The aim of the present study was to examine the effects of atorvastatinon p38 phosphorylation and cardiac remodeling after myocardial infarction in rats. A total of 43 rats were randomly divided into the control, sham operation, post-modeling medication (medication) and post-modeling non-medication (non-medication) groups. The control group did not receive any treatment. Anterior descending arteries of the rats in the medication and non-medication groups were ligated, and threading at the anterior descending arteries was conducted for the rats in the sham operation group. Atorvastatin (10 mg/kg) was given daily to the rats in the medication group, and an equivalent amount of normal saline was given daily to the rats in the sham operation group. Four weeks later, the cardiac function, morphological changes in the myocardial cells, and the expression of tumor necrosis factor-α (TNF-α) and p38 in each group was detected. At 4 weeks after treatment, the myocardial infarction size, fibrosis and myocardial necrosis of the rats in the medication group was examined compared with those in the non-medication group (P<0.05). The cardiac function of the rats in the non-medication group was significantly lower than that of the rats in the control and sham groups (P<0.05), while it was obviously elevated in the medication group compared with that in the non-medication group (P<0.05). The expression of TNF-α and phosphorylated p38 of the left ventricle in the non-medication group was higher than that in the control group (P<0.05), while it was obviously reduced in the non-medication group compared with that in the control group (P<0.05). Atorvastatin can improve cardiac remodeling after myocardial infarction in rats, which may be associated with its inhibition of p38 phosphorylation and its decrease of TNF-α expression.

Protective effects of beef decoction rich in carnosine on cerebral ischemia injury by permanent middle cerebral artery occlusion in rats.

Inflammation has a role in the cerebral injury induced by ischemia and the present study aimed to determine the mechanism of the protective effect of beef decoction (BD) with carnosine against it. A rat model of permanent middle cerebral artery occlusion was established using a suture method in the vehicle and each of the BD groups. In experiment 1, 72 Sprague Dawley (SD) rats were randomly divided into three groups: Sham, vehicle and BD-treated group. Rats in the BD group were given 600 mg/kg BD by oral gavage for 1, 3 and 7 days. The sham and vehicle group rats received an equivalent amount of normal saline. In experiment 2, 60 SD rats were randomly divided into six groups: Sham-operated I, sham-operated II, vehicle, low-dose BD, medium-dose BD and high-dose BD group. Rats in the low-, medium- and high-dose BD groups were given BD at the dose of 200, 400 and 600 mg/kg, respectively, by oral gavage for 7 days. Rats in the sham-operated II group were given 600 mg/kg BD. Rats in the sham-operated I group and vehicle group were given the same volume of normal saline by oral gavage. The body weight, neurological deficits and infarct volume were recorded at 1, 3 and 7 days after the operation. Furthermore, the effect of different doses of BD on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-4 (IL-4) levels in peripheral blood was measured at 7 days. BD-treated rats showed less neurological deficits and a smaller infarct volume at 7 days. BD at 400 and 600 mg/kg significantly decreased the infarct volume in rats. At 600 mg/kg BD, a decline in IL-6, TNF-α, IFN-γ and an increase in IL-4 expression was observed in the BD groups, while no difference in body weight and neurological dysfunction was detected. In conclusion, BD is a neuroprotective agent that may be used as a supplement treatment of ischemic stroke.

Correlations between physiological parameters related with kidney function and minute-by-minute urine output.

Recently, devices capable of measuring minute-by-minute urine output (UOm) have become available. It is not known how UOm correlates with physiological parameters in normal conditions and in disease states characterized by vascular dysfunction. This paper analyzes correlations between UOm and physiological parameters related to kidney perfusion to provide some insight about UOm pathophysiological interpretation and its relationship with renal blood flow. We studied 14 male pigs were anesthetized, tracheostomized, and mechanically ventilated. Mean systemic blood pressure (PART ), mean pulmonary artery blood pressure (PPA ), carotid artery blood flow (QCA ), as well as total (QREN ), cortical (QCOR ) and medullary (QMED ) renal blood flows, and the renal resistive index (RRI) were measured or calculated. Animals received an intravenous dose of live E. coli for the induction of sepsis (septic group), or an equivalent amount of normal saline (nonseptic group). Three groups were studied: nonseptic (n = 6) and septic (n = 4), both receiving for resuscitation NaCl 0.9% at 4 mL/kg per h; and septic (n = 4), receiving for resuscitation NaCl 0.9% at 17 mL/kg per h. Animals were monitored for 5 h after the induction of sepsis. In septic animals, UOm was strongly positively correlated with QREN (Kendall's τ = 0.770, P < 0.05), QCOR (τ = -0.566, P < 0.05) and QMED (τ = 0.632, P < 0.05); and negatively correlated with PPA (τ = -0.524, P < 0.05) and RRI (τ = -0.672, P < 0.05). Control animals exhibited weaker correlations. UOm is a good physiological surrogate marker of total and regional renal blood flows and vascular resistance, particularly under septic conditions, probably reflecting glomerulo-tubular dysfunction in sepsis.

Rhodiola rosea suppresses thymus T-lymphocyte apoptosis by downregulating tumor necrosis factor-α-induced protein 8-like-2 in septic rats.

In recent years, several studies have shown that Rhodiola rosea can enhance cellular immunity and humoral immune function in mice, and thus, it has become a research hotspot. However, its underlying mechanism of action has remained elusive. The present study investigated whether Rhodiola rosea was able to downregulate the expression of tumor necrosis factor-α-inducible protein 8-like 2 (TIPE2), thereby inhibiting the expression of apoptotic genes, attenuating T-lymphocyte apoptosis and improving immunity in septic mice. A mouse model of caecal ligation and puncture (CLP)-induced sepsis was established, and animals in the treatment group were pre-treated with an intraperitoneal injection of Rhodiola rosea extract, while animals in the control group and sham-operated group were injected with an equivalent amount of normal saline. TIPE2, B-cell lymphoma 2 (Bcl-2), Fas and Fas ligand (FasL) mRNA and protein levels in thymic T cells were determined using reverse transcription quantitative polymerase chain reaction and western blot analysis, respectively. Furthermore, the thymus T-lymphocyte apoptosis rate, thymus T-lymphocyte count and thymus T-lymphocyte sub-sets were assessed using flow cytometry. Levels of T-helper cell type 1 (Th1) cytokines [Interleukin (IL)-2, IL-12 and interferon (IFN)-γ] and Th2 cytokines (IL-4 and IL-10) were determined using ELISA. The results showed that, compared to that in the CLP group, the expression of TIPE2, Fas and FasL in the treatment group was significantly decreased, while the expression of Bcl-2 was increased (P<0.05). The thymus lymphocyte count in the CLP group was significantly higher compared with that in the treatment group (P<0.05). Furthermore, the apoptotic rate of thymus T-lymphocytes in the treatment group was significantly lower than that in the CLP group (P<0.05). In addition, treatment with Rhodiola rosea rescued decreased in the counts of the CD3+ T and CD4+ T sub-sets of thymus T lymphocytes in the CLP group (P<0.05), while not affecting the increased levels of Th2 cytokines (IL-4 and IL-10) in the CLP group compared with those in the control groups. In addition, the Th1 cytokines (IL-12, IL-2 and IFN-γ) were significantly increased (P<0.05) in the CLP group, and treatment with Rhodiola rosea led to further increases. The thymus index of septic mice treated with Rhodiola rosea as well as their survival rate were improved as compared with those in the CLP group. These findings suggested that Rhodiola rosea has protective effects against sepsis by decreasing apoptosis, increasing Th1 cytokines and enhancing the host’s immunity via the regulation of TIPE2 expression.

Intravesical botulinum toxin-A injections reduce bladder pain of interstitial cystitis/bladder pain syndrome refractory to conventional treatment - A prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial.

Intravesical onabotulinumtoxinA (BoNT-A) injection is a beneficial treatment for interstitial cystitis/bladder pain syndrome (IC/BPS), yet its therapeutic efficacy remains to be validated. This study tests efficacy and safety of intravesical BoNT-A injections for treatment of IC/BPS. A multicenter, randomized, double-blind, placebo-controlled trial in patients with IC/BPS refractory to conventional treatment. Patients were randomized in a 2:1 ratio to hydrodistention plus suburothelial injections of BoNT-A 100 U (Botox group) or the equivalent amount of normal saline (N/S group). The primary endpoint was a decrease in pain assessed using a visual analog scale (VAS) at week 8 after treatment. Secondary endpoints included voiding diary and urodynamic variables. The Wilcoxon sign rank and rank sum tests were used for statistical analyses. A total of 60 patients (8 males, 52 females, age 50.8 ± 13.9 years) including 40 in the Botox and 20 in the N/S groups were enrolled. At week 8, a significantly greater reduction of pain was observed in the Botox group compared to the N/S group (-2.6 ± 2.8 vs. -0.9 ± 2.2, P = 0.021). The other variables did not differ significantly between groups except for cystometric bladder capacity, which was increased significantly in the Botox group. The overall success rates were 63% (26/40) in the Botox group and 15% (3/20) in the N/S group (P = 0.028). Adverse events did not differ between the groups. Intravesical injections of 100 U of BoNT-A effectively reduced bladder pain symptoms in patients with IC/BPS. The adverse events were acceptable. Neurourol. Urodynam. 35:609-614, 2016. © 2015 Wiley Periodicals, Inc.

Treatment and mechanism of BMMSCs on deep II degree scald of hamster skin

In this study, we examined the treatment and mechanism of BMMSC on a deep II degree scald of the hamster skin. A deep II degree scald model on the skin of 40 hamsters was duplicated and divided randomly into a stem cell plantation group (group A) and model control group (group B). Skin cells were cultured in vitro until the allogeneic BMMSCs of the 5th generation formed with a cell count of 1 x 10(7)/mL. Local injection plus liquid supernatant smearing was used to plant the cells into the position of the scald in the stem cell plantation group. The control group was given an equivalent amount of normal saline to observe the healing action, and 5 samples were taken in each group after 1, 3, 7, and 14 days for hematoxylin and eosin staining for physiological observation. Polymerase chain reaction was used to detect the amount of chymotrypsin in mast cells. The speed of healing in the stem cell transplantation group was greater than that in the control group; staining results showed that the quality of healing in the transplantation group was better than that in the control group. Chymotrypsin expression was detected in both groups, reaching a peak on day 3. BMMSCs can accelerate wound healing, and chymotrypsin in mast cells may participate in the wound healing process.

Histopathological Changes in Multiple Fetal Tissues Exposed In-Utero to Zidovudine

Objective: Zidovudine, the first antiretroviral drug is used to prevent vertical transmission of HIV infection. Without any adequate proof of its safety to fetus, the drug was administered to pregnant women. The present experiment aims to study at the light microscopic level, the effect of zidovudine in fetus exposed in-utero to the drug. Material and method: Sixty Swiss mice were divided into two groups of control (n=20) and experimental (n=40). A dose of 50 mg/kg/day was administered orally to experimental group and an equivalent amount of normal saline to control group. Drug was administered from day 8 to day 16 of gestation and on day 19 the animal was sacrificed. Fetus collected after laparotomy were fixed in 10% neutral formalin and then subjected to light microscopic study to assess the histopathological changes. H&E stained sections of liver, lung, kidney, brain and maternal ovary was analysed. Result: Fatty degeneration of liver, degenerative changes in kidney section, dilatation of alveoli with thinning of alveolar wall, microcystic degeneration in cerebral cortex was observed. The maternal ovary of experimental group had small corpus luteum. Conclusion: Multiple tissues are affected by in-utero administration of ZDV. Further study at ultrastructural level is needed.

A study on the effect of aqueous extract of &lt;i&gt;Lobelia chinensis&lt;/i&gt; on colon precancerous lesions in rats

This paper studies the effects of Lobelia chinensis on colon precancerous lesions and on colonic epithelial proliferation and apoptosis in DMH-induced rats. After two weeks of feeding, 50 Wistar rats were randomly divided into five groups, namely the normal group, model group, Lobelia chinensis low-dose group, medium-dose group and high-dose group. Lobelia chinensis was made into ACF model, and administered to experimental groups for 10 consecutive weeks. Control group was given equivalent amount of normal saline. After feeding for 10 weeks, the rats in each group were sacrificed and the changes in colonic ACF number of rats in experimental groups were observed, and the inhibition rates were calculated. The results showed that among the rats fed for 24 h and 48 h, the number of apoptotic cells in colonic crypts of rats in DMH group did not differ significantly from the control group, while the difference was obvious between the control group and Lobelia chinensis treatment groups. The medium and high doses, that is, 0.45 g/kg and 1.35 g/kg can significantly inhibit ACF formation (P<0.01). The inhibition rates of low, medium and high doses were 8.12%, 59.42% and 65.44%, respectively.