| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Forskningsöversikt (refereegranskat)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
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| 3. |
- DeAngelis, Nicola, et al.
(författare)
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2020 WSES guidelines for the detection and management of bile duct injury during cholecystectomy
- 2021
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Ingår i: World Journal of Emergency Surgery. - : BMC. - 1749-7922. ; 16:1
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Forskningsöversikt (refereegranskat)abstract
- Bile duct injury (BDI) is a dangerous complication of cholecystectomy, with significant postoperative sequelae for the patient in terms of morbidity, mortality, and long-term quality of life. BDIs have an estimated incidence of 0.4-1.5%, but considering the number of cholecystectomies performed worldwide, mostly by laparoscopy, surgeons must be prepared to manage this surgical challenge. Most BDIs are recognized either during the procedure or in the immediate postoperative period. However, some BDIs may be discovered later during the postoperative period, and this may translate to delayed or inappropriate treatments. Providing a specific diagnosis and a precise description of the BDI will expedite the decision-making process and increase the chance of treatment success. Subsequently, the choice and timing of the appropriate reconstructive strategy have a critical role in long-term prognosis. Currently, a wide spectrum of multidisciplinary interventions with different degrees of invasiveness is indicated for BDI management. These World Society of Emergency Surgery (WSES) guidelines have been produced following an exhaustive review of the current literature and an international expert panel discussion with the aim of providing evidence-based recommendations to facilitate and standardize the detection and management of BDIs during cholecystectomy. In particular, the 2020 WSES guidelines cover the following key aspects: (1) strategies to minimize the risk of BDI during cholecystectomy; (2) BDI rates in general surgery units and review of surgical practice; (3) how to classify, stage, and report BDI once detected; (4) how to manage an intraoperatively detected BDI; (5) indications for antibiotic treatment; (6) indications for clinical, biochemical, and imaging investigations for suspected BDI; and (7) how to manage a postoperatively detected BDI.
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| 4. |
- Abdalla, Mohammed A., et al.
(författare)
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Effect of pharmacological interventions on lipid profiles and C-reactive protein in polycystic ovary syndrome : A systematic review and meta-analysis
- 2022
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Ingår i: Clinical Endocrinology. - : John Wiley & Sons. - 0300-0664 .- 1365-2265. ; 96:4, s. 443-459
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Forskningsöversikt (refereegranskat)abstract
- Context: Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age. It is associated with dyslipidaemia and elevated plasma C-reactive protein (CRP), which increase the risks of cardiovascular disease (CVD).Objective: To review the existing evidence on the effects of different pharmacological interventions on lipid profiles and CRP of women with PCOS.Data Sources: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library, and Web of Science in April 2020 and updated the results in March 2021.Study Selection: The study included randomized controlled trials (RCTs) and follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA).Data Extraction: Two independent researchers extracted data and assessed for risk of bias using the Cochrane risk of bias tool. Covidence systematic review software were used for blinded screening and study selection.Data Synthesis: In 29 RCTs, there were significant reductions in triglycerides with atorvastatin versus placebo [mean difference (MD): -0.21 mmol/L; 95% confidence interval (CI): -0.39, -0.03, I-2 = 0%, moderate grade evidence]. Significant reductions were seen for low-density lipoprotein cholesterol (LDL-C) with metformin versus placebo [standardized mean difference (SMD): -0.41; 95% CI: -0.85, 0.02, I-2 = 59%, low grade evidence]. Significant reductions were also seen for total cholesterol with saxagliptin versus metformin (MD: -0.15 mmol/L; 95% CI: -0.23, -0.08, I-2 = 0%, very low grade evidence). Significant reductions in C-reactive protein (CRP) were seen for atorvastatin versus placebo (MD: -1.51 mmol/L; 95% CI: -3.26 to 0.24, I-2 = 75%, very low-grade evidence).Conclusion: There were significant reductions in the lipid parameters when metformin, atorvastatin, saxagliptin, rosiglitazone and pioglitazone were compared with placebo or other agents. There was also a significant reduction of CRP with atorvastatin.
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| 5. |
- Abdalla, Mohammed Altigani, et al.
(författare)
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Impact of metformin on the clinical and metabolic parameters of women with polycystic ovary syndrome : a systematic review and meta-analysis of randomised controlled trials
- 2022
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Ingår i: Therapeutic Advances in Endocrinology and Metabolism. - : Sage Publications. - 2042-0188 .- 2042-0196. ; 13
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Forskningsöversikt (refereegranskat)abstract
- Context: Polycystic ovary syndrome (PCOS) is one of the commonest endocrine disorders affecting women of reproductive age, and metformin is a widely used medication in managing this condition.Aim: To review the available literature comprehensively on the therapeutic impact of metformin on the clinical and metabolic parameters of women with PCOS.Data source: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library and the Web of Science and selected sources for grey literature from their inception to April 2020. An updated search in PubMed was performed in June 2022.Data synthesis: Two reviewers selected eligible studies and extracted data, and the review is reported following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).Results: In 24 eligible randomised controlled trials (RCTs) involving 564 participants who received metformin therapy, metformin was associated with significant reduction in body weight by 3.13 kg (95% CI: -5.33, -0.93), body mass index (BMI) by 0.82 kg/m(2) (95% CI: -1.22, -0.41), fasting blood glucose [standardised mean difference (SMD): -0.23; 95% CI: -0.40, -0.06], low-density lipoprotein cholesterol (LDL-C) (SMD: -0.41; 95% CI: -0.85, 0.03), total testosterone (SMD: -0.33; 95% CI: -0.49, -0.17), androstenedione (SMD: -0.45; 95% CI: -0.70, -0.20), 17-hydroxyprogesterone (17-OHP) (SMD: -0.58; 95% CI: -1.16, 0.00) and increase the likelihood of clinical pregnancy rate [odds ratio (OR): 3.00; 95% CI: 1.95, 4.59] compared with placebo.Conclusion: In women with PCOS, metformin use has shown a positive impact in reducing body weight, BMI, total testosterone, androstenedione, 17-OHP, LDL-C, fasting blood glucose and increasing the likelihood of pregnancy in women with PCOS.
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| 6. |
- Abdalla, Mohammed A., et al.
(författare)
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Impact of pharmacological interventions on anthropometric indices in women with polycystic ovary syndrome : A systematic review and meta-analysis of randomized controlled trials
- 2022
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Ingår i: Clinical Endocrinology. - : John Wiley & Sons. - 0300-0664 .- 1365-2265. ; 96:6, s. 758-780
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Forskningsöversikt (refereegranskat)abstract
- Context: Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age and is associated with increased body weight.Objective: To review the literature on the effect of different pharmacological interventions on the anthropometric indices in women with PCOS.Data sources: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library, and the Web of Science in April 2020 with an update in PubMed in March 2021.Study selection: The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)2020.Data extraction: Reviewers extracted data and assessed the risk of bias using the Cochrane risk of bias tool.Results: 80 RCTs were included in the meta-analysis. Metformin vs placebo showed significant reduction in the mean body weight (MD: -3.13 kg; 95% confidence interval [CI]: -5.33 to -0.93, I-2 = 5%) and the mean body mass index (BMI) (MD: -0.75 kg/m(2); 95% CI: -1.15 to -0.36, I-2 = 0%). There was a significant reduction in the mean BMI with orlistat versus placebo (MD: -1.33 kg/m(2); 95% CI: -2.16 to -0.66, I-2 = 0.0%), acarbose versus metformin (MD: -1.26 kg/m(2); 95% CI: -2.13 to -0.38, I-2 = 0%), and metformin versus pioglitazone (MD: -0.91 kg/m(2); 95% CI: -1.62 to -0.19, I-2 = 0%). A significant increase in the mean BMI was also observed in pioglitazone versus placebo (MD: + 2.59 kg/m(2); 95% CI: 1.78-3.38, I-2 = 0%) and in rosiglitazone versus metformin (MD: + 0.80 kg/m(2); 95% CI: 0.32-1.27, I-2 = 3%). There was a significant reduction in the mean waist circumference (WC) with metformin versus placebo (MD: -1.21 cm; 95% CI: -3.71 to 1.29, I-2 = 0%) while a significant increase in the mean WC with pioglitazone versus placebo (MD: + 5.45 cm; 95% CI: 2.18-8.71, I-2 = 0%).Conclusion: Pharmacological interventions including metformin, sitagliptin, pioglitazone, rosiglitazone orlistat, and acarbose have significant effects on the anthropometric indices in women with PCOS.
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| 7. |
- Abdalla, Mohammed Altigani, et al.
(författare)
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Impact of pharmacological interventions on biochemical hyperandrogenemia in women with polycystic ovary syndrome : a systematic review and meta-analysis of randomised controlled trials
- 2022
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Ingår i: Archives of Gynecology and Obstetrics. - : Springer. - 0932-0067 .- 1432-0711.
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Forskningsöversikt (refereegranskat)abstract
- Context: Polycystic ovary syndrome (PCOS) is a complex endocrine disease that affects women of reproductive age and is characterised by biochemical and clinical androgen excess.Aim: To evaluate the efficacy of pharmacological interventions used to decrease androgen hormones in women with PCOS.Data source: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library and the Web of Science from inception up to March 2021. Data synthesis Two reviewers selected eligible studies and extracted data, and the review is reported according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).Results: Of the 814 randomised clinical trials (RCTs) located in the search, 92 met the eligibility criteria. There were significant reductions in total testosterone level with metformin versus (vs) placebo (SMD: - 0.33; 95% CI - 0.49 to - 0.17, p < 0.0001, moderate grade evidence) and dexamethasone vs placebo (MD:-0.86 nmol/L; 95% CI - 1.34 to - 0.39, p = 0.0004, very low-grade evidence). Significant reductions in the free testosterone with sitagliptin vs placebo (SMD: - 0.47; 95% CI - 0.97 to 0.04, p = 0.07, very low-grade evidence), in dehydroepiandrosterone sulphate (DHEAS) with flutamide vs finasteride (MD: - 0.37 mu g/dL; 95% CI - 0.05 to - 0.58, p = 0.02, very low-grade evidence), a significant reduction in androstenedione (A4) with rosiglitazone vs placebo (SMD: - 1.67; 95% CI - 2.27 to - 1.06; 59 participants, p < 0.00001, very low-grade evidence), and a significant increase in sex hormone-binding globulin (SHBG) with oral contraceptive pill (OCP) (35 mu g Ethinyl Estradiol (EE)/2 mg cyproterone acetate (CPA)) vs placebo (MD: 103.30 nmol/L; 95% CI 55.54-151.05, p < 0.0001, very low-grade evidence) were observed.Conclusion: Metformin, OCP, dexamethasone, flutamide, and rosiglitazone use were associated with a significant reduction in biochemical hyperandrogenemia in women with PCOS, though their individual use may be limited due to their side effects.PROSPERO registration No CRD42020178783.
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| 8. |
- Abdalla, Mohammed A., et al.
(författare)
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Impact of pharmacological interventions on insulin resistance in women with polycystic ovary syndrome : A systematic review and meta-analysis of randomized controlled trials
- 2022
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Ingår i: Clinical Endocrinology. - : John Wiley & Sons. - 0300-0664 .- 1365-2265. ; 96:3, s. 371-394
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Forskningsöversikt (refereegranskat)abstract
- Objective: Polycystic ovary syndrome (PCOS) is a complex endocrine condition affecting women of reproductive age. It is characterized by insulin resistance and is a major risk factor for type 2 diabetes mellitus (T2DM). The objective was to review the literature on the effect of different pharmacological interventions on insulin resistance in women with PCOS.Design: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library and the Web of Science in April 2020 and updated in March 2021. The study follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-ana. Reviwers extracted data and assessed the risk of bias using the Cochrane risk of bias tool.Results: In 58 randomized controlled trials there were significant reductions in the fasting blood glucose (FBG) with metformin versus placebo (standardized mean difference [SMD]: -0.23; 95% confidence interval [CI]: -0.40, -0.06; I-2 = 0%, low-grade evidence), and acarbose versus metformin (mean difference [MD]: -10.50 mg/dl; 95% CI: -15.76, -5.24; I-2 = 0%, low-grade evidence). Significant reductions in fasting insulin (FI) with pioglitazone versus placebo (SMD: -0.55; 95% CI: -1.03, -0.07; I-2 = 37%; p = .02, very-low-grade evidence). A significant reduction in homoeostatic model assessment of insulin resistance (HOMA-IR) was seen with exenatide versus metformin (MD: -0.34; 95% CI: -0.65, -0.03; I-2 = 0%, low-grade evidence). No effect on homoeostatic model assessment of beta cells (HOMA-B) was observed.Conclusions: Pharmacological interventions, including metformin, acarbose, pioglitazone and exenatide have significant effects on FBG, FI, HOMA-IR but not on HOMA-B.
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| 9. |
- Alfalasi, Maryam, et al.
(författare)
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Effect of Nitric Oxide Pathway Inhibition on the Evolution of Anaphylactic Shock in Animal Models : A Systematic Review
- 2022
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Ingår i: Biology. - : MDPI. - 2079-7737. ; 11:6
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Forskningsöversikt (refereegranskat)abstract
- Simple Summary: Anaphylactic shock (AS) is the most serious consequence of anaphylaxis, with life-threatening sequelae including hypovolemia, shock, and arrhythmias. The literature lacks evidence for the effectiveness of interventions other than epinephrine in the acute phase of anaphylaxis. Our objective was to assess, through a systematic review, how inhibition of nitric oxide (NO) pathways affects blood pressure, and whether such blockade improves survival in AS animal models. AS was induced in all included studies after or before drug administration that targeted blockade of the NO pathway. In all animal species studied, the induction of AS caused a reduction in arterial blood pressure. However, the results show different responses to the inhibition of nitric oxide pathways. Overall, seven of fourteen studies using inhibition of nitric oxide pathways as pre-treatment before induction of AS showed improvement of survival and/or blood pressure. Four post-treatment studies from eight also showed positive outcomes. This review did not find strong evidence to propose modulation of blockade of the NO/cGMP pathway as a definitive treatment for AS in humans. Well-designed in vivo AS animal pharmacological models are needed to explore the other pathways involved, supporting the concept of pharmacological modulation.Abstract: Nitric oxide (NO) induces vasodilation in various types of shock. The effect of pharmacological modulation of the NO pathway in anaphylactic shock (AS) remains poorly understood. Our objective was to assess, through a systematic review, whether inhibition of NO pathways (INOP) was beneficial for the prevention and/or treatment of AS. A predesigned protocol for this systematic review was published in PROSPERO (CRD42019132273). A systematic literature search was conducted till March 2022 in the electronic databases PubMed, EMBASE, Scopus, Cochrane and Web of Science. Heterogeneity of the studies did not allow meta-analysis. Nine hundred ninety unique studies were identified. Of 135 studies screened in full text, 17 were included in the review. Among six inhibitors of NO pathways identified, four blocked NO synthase activity and two blocked guanylate cyclase downstream activity. Pre-treatment was used in nine studies and post-treatment in three studies. Five studies included both pre-treatment and post-treatment models. Overall, seven pre-treatment studies from fourteen showed improvement of survival and/or arterial blood pressure. Four post-treatment studies from eight showed positive outcomes. Overall, there was no strong evidence to conclude that isolated blockade of the NO/cGMP pathway is sufficient to prevent or restore anaphylactic hypotension. Further studies are needed to analyze the effect of drug combinations in the treatment of AS.
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| 10. |
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