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Article ; Online: Ameliorative Potential of Hydroethanolic Leaf Extract of

Ajayi, Lydia / Ayeleso, Ademola / Oyedepo, Temitope / Mukwevho, Emmanuel

2021 Volume 26, Issue 11

Abstract: Background: There is an increasing need for botanicals to be used as an alternative and complementary medicine in the management of male infertility. Male infertility has been a major health/social challenge to people all over the world. This study, ... ...

Abstract	Background: There is an increasing need for botanicals to be used as an alternative and complementary medicine in the management of male infertility. Male infertility has been a major health/social challenge to people all over the world. This study, therefore, investigated the ameliorative potential of hydroethanolic leaf extract of Methods: Thirty male Wistar rats were randomly allotted into six groups (n = 5). Group I (Normal control), Group II (300 mg/kg b.w. d-galactose), Group III and IV (250 and 500 mg/kg b.w. HELEPN, respectively), Group V and VI (both received 300 mg/kg b.w. of d-galactose with 250 and 500 mg/kg b.w of HELEPN, respectively). d-galactose administration started two weeks prior to HELEPN treatment which lasted for six weeks. All assays were carried out using established protocols. Results: Administration of HELEPN at 250mg/kg and 500mg/kg concomitantly with d-galactose improved paired and relative testicular weights, levels of gonadotropins (LH and FSH) and testosterone, and poor sperm quality. HELEPN treatment reduced the levels of oxidative stress biomarkers (MDA, 8-OHDG, and AGEs) and inflammatory response (TNF-alpha and NO) to normal, as well as restoring the reduced activities of antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase). In addition, HELEPN treatment mitigated testicular DNA fragmentation and down-regulated caspase 3-activities. HELEPN at 500 mg/kg was observed to have the greatest ameliorative effect. Conclusion: HELEPN protects against d-galactose-induced testicular injury through antioxidative, anti-inflammatory, and antiapoptotic mechanisms.
MeSH term(s)	Animals ; Apocynaceae/chemistry ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Ethanol/chemistry ; Galactose/adverse effects ; Gonadotropins/metabolism ; Humans ; Infertility, Male/chemically induced ; Infertility, Male/drug therapy ; Infertility, Male/metabolism ; Male ; Organ Size/drug effects ; Plant Extracts/administration & dosage ; Plant Extracts/chemistry ; Plant Extracts/pharmacology ; Plant Leaves/chemistry ; Random Allocation ; Rats ; Rats, Wistar ; Semen Analysis ; Testis/drug effects ; Testis/injuries ; Testis/metabolism ; Testosterone/metabolism
Chemical Substances	Gonadotropins ; Plant Extracts ; Ethanol (3K9958V90M) ; Testosterone (3XMK78S47O) ; Galactose (X2RN3Q8DNE)
Language	English
Publishing date	2021-06-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules26113424
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Article ; Online: Impact of hypoxia on male reproductive functions.

Oyedokun, P A / Akhigbe, R E / Ajayi, L O / Ajayi, A F

Molecular and cellular biochemistry

2022 Volume 478, Issue 4, Page(s) 875–885

Abstract: Male reproductive functions, which include testicular steroidogenesis, spermatogenesis, and sexual/erectile functions are key in male fertility, but may be adversely altered by several factors, including hypoxia. This review demonstrates the impact of ... ...

Abstract	Male reproductive functions, which include testicular steroidogenesis, spermatogenesis, and sexual/erectile functions are key in male fertility, but may be adversely altered by several factors, including hypoxia. This review demonstrates the impact of hypoxia on male reproductive functions. Acute exposure to hypoxia promotes testosterone production via stimulation of autophagy and upregulation of steroidogenic enzymes and voltage-gated L-type calcium channel, nonetheless, chronic exposure to hypoxia impairs steroidogenesis via suppression of the hypothalamic-pituitary-testicular axis. Also, hypoxia distorts spermatogenesis and reduces sperm count, motility, and normal forms via upregulation of VEGF and oxidative stress-sensitive signaling. Furthermore, hypoxia induces sexual and erectile dysfunction via a testosterone-dependent downregulation of NO/cGMP signaling and upregulation of PGE1/TGFβ1-driven penile endothelial dysfunction. Notably, hypoxia programs male sexual function and spermatogenesis/sperm quality via feminization and demasculinization of males and oxidative stress-mediated alteration in sperm DNA methylation. Since oxidative stress plays a central role in hypoxia-induced male reproductive dysfunction, studies exploring the effects of antioxidants and upregulation of transcription of antioxidants on hypoxia-induced male reproductive dysfunction are recommended.
MeSH term(s)	Male ; Humans ; Antioxidants/pharmacology ; Semen/metabolism ; Testis/metabolism ; Spermatogenesis/physiology ; Testosterone/pharmacology ; Oxidative Stress
Chemical Substances	Antioxidants ; Testosterone (3XMK78S47O)
Language	English
Publishing date	2022-09-15
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	184833-1
ISSN	1573-4919 ; 0300-8177
ISSN (online)	1573-4919
ISSN	0300-8177
DOI	10.1007/s11010-022-04559-1
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Zs.A 892: Show issues

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Article ; Online: Codeine alters female reproductive function by targeting ovarian steroidogenesis and folliculogenesis via the induction of oxidative stress, inflammation, and apoptosis.

Akhigbe, R E / Ebiwonjumi, O S / Ajayi, L O / Ajayi, A F

Reproductive toxicology (Elmsford, N.Y.)

2022 Volume 109, Page(s) 1–9

Abstract: The rise in the abuse of codeine raises concerns about its impact on the health of users, and little has appeared on its effect on the female reproductive function. Therefore, this study evaluated the impact of codeine on female reproductive function. We ...

Abstract	The rise in the abuse of codeine raises concerns about its impact on the health of users, and little has appeared on its effect on the female reproductive function. Therefore, this study evaluated the impact of codeine on female reproductive function. We administered codeine at low (2 mg/kg) and high (5 mg/kg) doses to female animals prior to mating for 8 weeks. In comparison with a vehicle-treated group, we then assessed the impact of codeine on body weight gain and ovarian weight, female sexual behaviour, ovarian steroidogenesis, and folliculogenesis. The role of oxidative stress, inflammation, and apoptosis were also evaluated. Codeine at either dose elicited a profound deficit in the absolute and relative ovarian weight, indicative of ovarian toxicity. Also, codeine induced female sexual dysfunction, and suppressed ovarian steroidogenesis and folliculogenesis, with degeneration of the ovarian cytoarchitecture and follicles. The effects of codeine were associated with a rise in ovarian hydroxyl radical generation and oxidative stress, evident by an increase in ovarian malondialdehyde, a reduction in reduced glutathione, and a decline in the activities of ovarian enzymatic antioxidants. In addition, codeine triggered an increase in the ovarian concentration of inflammatory cytokines, TNF-α and IL-1β, and myeloperoxidase activity. Furthermore, codeine caused an increase in 8-hydroxydeoxyguanosine (8OHdG), ovarian DNA fragmentation, and caspase-3 activity, suggestive of genotoxicity and apoptosis respectively. The current study provides some of the first evidence for the adverse effects of prolong codeine use on female sexual function, ovarian steroidogenesis, and folliculogenesis. It also emphasizes the reproductive health consequences of drug abuse.
MeSH term(s)	Animals ; Apoptosis ; Codeine/toxicity ; Female ; Inflammation/chemically induced ; Ovary ; Oxidative Stress
Chemical Substances	Codeine (UX6OWY2V7J)
Language	English
Publishing date	2022-02-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	639342-1
ISSN	1873-1708 ; 0890-6238
ISSN (online)	1873-1708
ISSN	0890-6238
DOI	10.1016/j.reprotox.2022.02.001
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Zs.A 2316: Show issues

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Article ; Online: Codeine exerts cardiorenal injury via upregulation of adenine deaminase/xanthine oxidase and caspase 3 signaling.

Akhigbe, R E / Ajayi, L O / Ajayi, A F

Life sciences

2020 Volume 273, Page(s) 118717

Abstract: Aims: Codeine treatment has been shown to be associated with glucolipid deregulation, though data reporting this are inconsistent and the mechanisms are not well understood. Perturbation of glutathione-dependent antioxidant defense and adenosine ... ...

Abstract	Aims: Codeine treatment has been shown to be associated with glucolipid deregulation, though data reporting this are inconsistent and the mechanisms are not well understood. Perturbation of glutathione-dependent antioxidant defense and adenosine deaminase (ADA)/xanthine oxidase (XO) signaling has been implicated in the pathogenesis of cardiometabolic disorders. We thus, hypothesized that depletion of glutathione contents and upregulation of ADA/XO are involved in codeine-induced glucolipid deregulation. The present study also investigated whether or not codeine administration would induce genotoxicity and apoptosis in cardiac and renal tissues. Materials and methods: Male New Zealand rabbits received per os distilled water or codeine, either in low dose (4 mg/kg) or high dose (10 mg/kg) for 6 weeks. Key findings: Codeine treatment led to reduced absolute and relative cardiac and renal mass independent of body weight change, increased blood glucose, total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL-C), as well as increased atherogenic indices and triglyceride-glucose index (TyG). Codeine administration significantly increased markers of cardiac and renal injury, as well as impaired cardiorenal functions. Codeine treatment also resulted in increased cardiac and renal malondialdehyde, Advanced Glycation Endproducts (AGE) and 8-hydroxydeoxyguanosine (8-OH-dG), and myeloperoxidase (MPO), ADA, XO, and caspase 3 activities. These observations were accompanied by impaired activities of cardiac and renal proton pumps. Significance: Findings of this study demonstrate that upregulation of ADA/XO and caspase 3 signaling are, at least partly, contributory to the glucolipid deregulation and cardiorenal injury induced by codeine.
MeSH term(s)	Acute Kidney Injury/chemically induced ; Acute Kidney Injury/metabolism ; Acute Kidney Injury/pathology ; Adenosine Deaminase/metabolism ; Animals ; Apoptosis ; Caspase 3/metabolism ; Codeine/toxicity ; Gene Expression ; Gene Expression Regulation, Enzymologic/drug effects ; Glucose/metabolism ; Heart/drug effects ; Heart/physiopathology ; Insulin Resistance ; Male ; Narcotics/toxicity ; Rabbits ; Triglycerides/metabolism ; Up-Regulation ; Xanthine Oxidase/metabolism
Chemical Substances	Narcotics ; Triglycerides ; Xanthine Oxidase (EC 1.17.3.2) ; Caspase 3 (EC 3.4.22.-) ; Adenosine Deaminase (EC 3.5.4.4) ; Glucose (IY9XDZ35W2) ; Codeine (UX6OWY2V7J)
Language	English
Publishing date	2020-11-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2020.118717
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Article: Usefulness and expectations on skills development and entrepreneurship among women of low socioeconomic status in Ogun State, Nigeria.

George, Tayo O / Oladosun, Muyiwa / Oyesomi, Kehinde / Orbih, Mary U / Nwokeoma, Nwanne / Iruonagbe, Charles / Ajayi, Lady / Lawal-Solarin, Esther

African journal of reproductive health

2023 Volume 25, Issue s5, Page(s) 171–187

Abstract: The acquisition of vocational training skills and entrepreneurial know-how is acknowledged as an added advantage and a safety net to navigate poverty, especially in dwindling economic recession time and massive unemployment. This study examined the ... ...

Abstract	The acquisition of vocational training skills and entrepreneurial know-how is acknowledged as an added advantage and a safety net to navigate poverty, especially in dwindling economic recession time and massive unemployment. This study examined the factors influencing the usefulness and perceived realization of skills development/empowerment to encourage more women's involvement in small scale businesses and promote its effect on poverty alleviation in households across Nigeria. Data collection involved a structured questionnaire and in-depth interviews conducted post-the vocational skill/empowerment training. The training was organized among Campus Keepers in a private university in Ogun State, Nigeria. Forty Campus Keepers were selected using the systematic sampling technique from a total population of 224, and 37 of the 40 selected voluntarily participated in this study. The Campus Keepers were women with low socioeconomic status who worked as cleaners on the university campus. Five of the Campus Keepers were purposively selected as key informants for the study. Results showed that respondents who had earlier knowledge and vocational skills training reported that it leads to self-employment. This view was higher for respondents who had more people in their household than those with fewer people (OR = 22.7 [CI= .56, 921.31]). The perception that the training can lead to additional income was lower for respondents who reported that either they or their spouses were sole breadwinners in their household than for those who reported that both/others/none were breadwinners (OR = .05 [CI=0, 1.2]). The odds that the skills development/empowerment training will result in perceived improved business was higher for respondents who gained more knowledge/information from the training than those who did not (OR=29.19 [CI = 1.1, 777.48]). Findings from the qualitative study suggest that key informants who participated in past training were yet to establish a profitable business of their dream fully. Governmental policy and program intervention that incorporates these findings will lead to increased participation of the target population in similar training in the future, leading to poverty alleviation towards achieving the SDGs for Nigeria.
Language	English
Publishing date	2023-08-10
Publishing country	Nigeria
Document type	Journal Article
ZDB-ID	2111906-5
ISSN	1118-4841
ISSN	1118-4841
DOI	10.29063/ajrh2021/v25i5s.16
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Article: Codeine exerts cardiorenal injury via upregulation of adenine deaminase/xanthine oxidase and caspase 3 signaling

Akhigbe, R.E / Ajayi, L.O / Ajayi, A.F

Life sciences. 2021 May 15, v. 273

2021

Abstract: Codeine treatment has been shown to be associated with glucolipid deregulation, though data reporting this are inconsistent and the mechanisms are not well understood. Perturbation of glutathione-dependent antioxidant defense and adenosine deaminase (ADA) ...

Abstract	Codeine treatment has been shown to be associated with glucolipid deregulation, though data reporting this are inconsistent and the mechanisms are not well understood. Perturbation of glutathione-dependent antioxidant defense and adenosine deaminase (ADA)/xanthine oxidase (XO) signaling has been implicated in the pathogenesis of cardiometabolic disorders. We thus, hypothesized that depletion of glutathione contents and upregulation of ADA/XO are involved in codeine-induced glucolipid deregulation. The present study also investigated whether or not codeine administration would induce genotoxicity and apoptosis in cardiac and renal tissues.Male New Zealand rabbits received per os distilled water or codeine, either in low dose (4 mg/kg) or high dose (10 mg/kg) for 6 weeks.Codeine treatment led to reduced absolute and relative cardiac and renal mass independent of body weight change, increased blood glucose, total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL-C), as well as increased atherogenic indices and triglyceride-glucose index (TyG). Codeine administration significantly increased markers of cardiac and renal injury, as well as impaired cardiorenal functions. Codeine treatment also resulted in increased cardiac and renal malondialdehyde, Advanced Glycation Endproducts (AGE) and 8-hydroxydeoxyguanosine (8-OH-dG), and myeloperoxidase (MPO), ADA, XO, and caspase 3 activities. These observations were accompanied by impaired activities of cardiac and renal proton pumps.Findings of this study demonstrate that upregulation of ADA/XO and caspase 3 signaling are, at least partly, contributory to the glucolipid deregulation and cardiorenal injury induced by codeine.
Keywords	adenine deaminase ; adenosine deaminase ; antioxidant activity ; apoptosis ; blood glucose ; body weight ; caspase-3 ; cholesterol ; codeine ; genotoxicity ; glutathione ; glycation ; low density lipoprotein ; malondialdehyde ; myeloperoxidase ; pathogenesis ; xanthine oxidase ; New Zealand
Language	English
Dates of publication	2021-0515
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-light
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2020.118717
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Article ; Online: Ureteral stricture rate after endoscopic treatments for urolithiasis and related risk factors: systematic review and meta-analysis.

Moretto, S / Saita, A / Scoffone, C M / Talso, M / Somani, B K / Traxer, O / Angerri, O / Knoll, T / Liatsikos, E / Herrmann, T R W / Ulvik, Ø / Skolarikos, A / Cracco, C M / Keller, E X / Paciotti, M / Piccolini, A / Uleri, A / Tailly, T / Carmignani, L /

Pietropaolo, A / Corrales, M / Lughezzani, G / Lazzeri, M / Fasulo, V / De Coninck, V / Arena, P / Nagele, U / Ferretti, S / Kronenberg, P / Perez-Fentes, D / Osther, P J / Goumas, I K / Acquati, P / Ajayi, L / Diana, P / Casale, P / Buffi, N M

World journal of urology

2024 Volume 42, Issue 1, Page(s) 234

Abstract: Purpose: We aimed to accurately determine ureteral stricture (US) rates following urolithiasis treatments and their related risk factors.: Methods: We conducted a systematic review and meta-analysis following the PRISMA guidelines using databases ... ...

Abstract	Purpose: We aimed to accurately determine ureteral stricture (US) rates following urolithiasis treatments and their related risk factors. Methods: We conducted a systematic review and meta-analysis following the PRISMA guidelines using databases from inception to November 2023. Studies were deemed eligible for analysis if they included ≥ 18 years old patients with urinary lithiasis (Patients) who were subjected to endoscopic treatment (Intervention) with ureteroscopy (URS), percutaneous nephrolithotomy (PCNL), or shock wave lithotripsy (SWL) (Comparator) to assess the incidence of US (Outcome) in prospective and retrospective studies (Study design). Results: A total of 43 studies were included. The pooled US rate was 1.3% post-SWL and 2.1% post-PCNL. The pooled rate of US post-URS was 1.9% but raised to 2.7% considering the last five years' studies and 4.9% if the stone was impacted. Moreover, the pooled US rate differed if follow-ups were under or over six months. Patients with proximal ureteral stone, preoperative hydronephrosis, intraoperative ureteral perforation, and impacted stones showed higher US risk post-endoscopic intervention with odds ratio of 1.6 (P = 0.05), 2.6 (P = 0.009), 7.1 (P < 0.001), and 7.47 (P = 0.003), respectively. Conclusions: The overall US rate ranges from 0.3 to 4.9%, with an increasing trend in the last few years. It is influenced by type of treatment, stone location and impaction, preoperative hydronephrosis and intraoperative perforation. Future standardized reporting and prospective and more extended follow-up studies might contribute to a better understanding of US risks related to calculi treatment.
MeSH term(s)	Humans ; Adolescent ; Constriction, Pathologic ; Prospective Studies ; Retrospective Studies ; Urolithiasis/surgery ; Ureteroscopy/adverse effects ; Ureteral Calculi/surgery ; Hydronephrosis
Language	English
Publishing date	2024-04-13
Publishing country	Germany
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Review
ZDB-ID	380333-8
ISSN	1433-8726 ; 0724-4983
ISSN (online)	1433-8726
ISSN	0724-4983
DOI	10.1007/s00345-024-04933-2
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Zs.A 1832: Show issues

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Article ; Online: Codeine-induced hepatic injury is via oxido-inflammatory damage and caspase-3-mediated apoptosis.

Akhigbe, R E / Ajayi, L O / Adelakun, A A / Olorunnisola, O S / Ajayi, A F

Molecular biology reports

2020 Volume 47, Issue 12, Page(s) 9521–9530

Abstract: Codeine (3-methylmorphine) is a known analgesic, antitussive, and antidiarrheal drug that is often abused for recreational purposes. It is metabolized in the liver via the cytochrome P450 system and thus hypothesized to induce hepatic injury especially ... ...

Abstract	Codeine (3-methylmorphine) is a known analgesic, antitussive, and antidiarrheal drug that is often abused for recreational purposes. It is metabolized in the liver via the cytochrome P450 system and thus hypothesized to induce hepatic injury especially when misused. Thus, the present study aimed at investigating changes in liver function, hepatic enzyme biomarker, proton pumps, antioxidant status, free radicals and TNF-α levels, as well as caspase 3 activities and hepatic DNA fragmentation after 6 weeks of oral codeine administration. Twenty-one male rabbits were randomized into 3 groups (n = 7). The control group had 1 ml of normal saline, while the low-dose and high-dose codeine groups received 4 and 10 mg/kg b.w of codeine respectively daily. The codeine-treated animals had significantly lower levels of serum proteins, increased activities of hepatic enzyme biomarkers and caspase 3, raised hepatic concentrations of free radicals and TNF-α, as well as increased hepatic DNA fragmentation. Codeine treatment also led to a significant decline in hepatic weight, activities of hepatic enzymatic antioxidant, Na
MeSH term(s)	Analgesics, Opioid/adverse effects ; Animals ; Apoptosis/drug effects ; Apoptosis/genetics ; Calcium-Transporting ATPases/genetics ; Calcium-Transporting ATPases/metabolism ; Caspase 3/genetics ; Caspase 3/metabolism ; Chemical and Drug Induced Liver Injury/etiology ; Chemical and Drug Induced Liver Injury/genetics ; Chemical and Drug Induced Liver Injury/metabolism ; Chemical and Drug Induced Liver Injury/pathology ; Codeine/adverse effects ; DNA Fragmentation ; Drug Administration Schedule ; Gene Expression Regulation ; Liver/drug effects ; Liver/metabolism ; Liver/pathology ; Liver Function Tests ; Male ; Nitric Oxide/metabolism ; Oxidation-Reduction/drug effects ; Oxidative Stress ; Rabbits ; Signal Transduction ; Sodium-Potassium-Exchanging ATPase/genetics ; Sodium-Potassium-Exchanging ATPase/metabolism ; Tumor Necrosis Factor-alpha/genetics ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	Analgesics, Opioid ; Tumor Necrosis Factor-alpha ; Nitric Oxide (31C4KY9ESH) ; Caspase 3 (EC 3.4.22.-) ; Calcium-Transporting ATPases (EC 7.2.2.10) ; Sodium-Potassium-Exchanging ATPase (EC 7.2.2.13) ; Codeine (UX6OWY2V7J)
Language	English
Publishing date	2020-11-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-020-05983-6
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Article ; Online: Pain management in adult patients with sickle cell disease in the emergency department: how does current practice compare with existing standards of care?

Gulilat, Markus / Tunji-Ajayi, Lanre / Thompson, Serena / Poku, Marie-Pascale / Appiah-Boateng, Ruth / Navarro, Nia / Sheikh, Hasan / Hulme, Jennifer / Bryan, Jennifer

CJEM

2023 Volume 25, Issue 10, Page(s) 836–844

Abstract: Purpose: Sickle cell disease (SCD) is an inherited blood disorder with a natural course punctuated by acute complications including painful vaso-occlusive episodes. The objectives were: (1) to determine what proportion of patients with SCD receive ... ...

Abstract	Purpose: Sickle cell disease (SCD) is an inherited blood disorder with a natural course punctuated by acute complications including painful vaso-occlusive episodes. The objectives were: (1) to determine what proportion of patients with SCD receive opioids within 30 min of triage as recommended by the current clinical recommendations and quality standard; and (2) to identify facilitators to timely opioid administration for patients with SCD. Methods: This was a retrospective observational study. The primary outcome was the proportion of visits in which patients received opioid analgesia within 30 min of triage. Secondary outcomes were time in minutes from triage to any analgesic administration and time from triage to first opioid administration. Patient demographics and ED encounter characteristics were included as potential associated variables. Results: There were 236 patient visits (by 103 patients) that met inclusion criteria. Patients received opioid analgesia within 30 min of triage in only 5.2% of visits. The median time from triage to opioid analgesia was 80 (IQR = 49.0, 125.5) minutes. Using an order set and receiving opioid analgesia prior to physician assessment were both associated with shorter times to opioid analgesia. Conclusion: Existing recommendations are that opioid analgesia be provided within 30 min of triage for patients with SCD and VOEs. Our data show this target is rarely met, even in a department in which SCD VOEs are a common presenting concern. The association of earlier opioid analgesia with order set use and administration prior to physician assessment highlights potential avenues for improving time to analgesia.
Language	English
Publishing date	2023-09-03
Publishing country	England
Document type	Journal Article
ISSN	1481-8043
ISSN (online)	1481-8043
DOI	10.1007/s43678-023-00579-y
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Article: Codeine-induced hepatic injury is via oxido-inflammatory damage and caspase-3-mediated apoptosis

Akhigbe, R. E / Ajayi, L. O / Adelakun, A. A / Olorunnisola, O. S / Ajayi, A. F

Molecular biology reports. 2020 Dec., v. 47, no. 12

2020

Abstract	Codeine (3-methylmorphine) is a known analgesic, antitussive, and antidiarrheal drug that is often abused for recreational purposes. It is metabolized in the liver via the cytochrome P450 system and thus hypothesized to induce hepatic injury especially when misused. Thus, the present study aimed at investigating changes in liver function, hepatic enzyme biomarker, proton pumps, antioxidant status, free radicals and TNF-α levels, as well as caspase 3 activities and hepatic DNA fragmentation after 6 weeks of oral codeine administration. Twenty-one male rabbits were randomized into 3 groups (n = 7). The control group had 1 ml of normal saline, while the low-dose and high-dose codeine groups received 4 and 10 mg/kg b.w of codeine respectively daily. The codeine-treated animals had significantly lower levels of serum proteins, increased activities of hepatic enzyme biomarkers and caspase 3, raised hepatic concentrations of free radicals and TNF-α, as well as increased hepatic DNA fragmentation. Codeine treatment also led to a significant decline in hepatic weight, activities of hepatic enzymatic antioxidant, Na⁺-K⁺-ATPase and Ca²⁺-ATPase. These alterations were more pronounced in high-dose codeine treated animals than in the low-dose group. Histopathological study showed moderate fatty degeneration of hepatic parenchyma, infiltration of the portal tract by inflammatory cells with dense collagen fibre deposition in codeine-treated animals. The present study revealed that codeine induced liver injury and hepatic DNA damage via caspase 3-dependent signaling by suppressing hepatic antioxidant status and enhancing free radical and TNF-α generation.
Keywords	DNA damage ; DNA fragmentation ; analgesics ; antioxidants ; apoptosis ; biomarkers ; blood serum ; caspase-3 ; codeine ; collagen ; cytochrome P-450 ; free radicals ; histopathology ; liver ; liver function ; males ; molecular biology
Language	English
Dates of publication	2020-12
Size	p. 9521-9530.
Publishing place	Springer Netherlands
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-020-05983-6
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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Bonn / Germany

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Inter-library loan at ZB MED