Different Doses of Calcium Supplementation to Prevent Gestational Hypertension and Pre-Eclampsia: A Systematic Review and Network Meta-Analysis

ObjectiveCalcium supplementation can prevent gestational hypertension and pre-eclampsia. However, besides the non-consensus of existing studies, there is a lack of evidence regarding the optimal dosing of calcium.MethodEight electronic databases, namely, the Cochrane Library, PUBMED, Web of Science, EMBASE, WANGFANG, VIP, CBM, and CNKI, were searched. The studies were retrieved from inception to July 13, 2021. Two researchers independently screened the literature, extracted data, and evaluated the methodological quality based on the inclusion criteria. In particular, the calcium supplementation doses were divided into three groups, namely, the high-dose (≥1.5 g), medium-dose (1.0–1.49 g), and the low-dose group (<1.0 g). The participants were also divided into high-risk and low-risk groups, according to the risk of developing gestational hypertension and pre-eclampsia.Results and DiscussionA total of 48 studies were incorporated into the final analyses. All doses of calcium supplementation reduced the incidence of gestational hypertension in the low-risk population (low dose - three studies; medium dose- 11 studies; high dose- 28 studies), whereas the medium-dose (three studies) reduced the incidence of gestational hypertension in high-risk groups. Moreover, a medium dose of calcium supplementation had the maximum effect in reducing gestational hypertension in low-risk and high-risk populations. The medium (three studies) and high doses (13 studies) of calcium supplementation reduced the incidence of pre-eclampsia in the low-risk groups. However, a medium-dose calcium supplementation maximally prevented pre-eclampsia in the low-risk population. The authenticity and reliability of the results were reduced due to the limitations of contemporary studies in terms of experimental design, result measurement, statistics, and evidence quality. Therefore, high-quality studies with larger sample size are required to evaluate further the effect of calcium supplementation in preventing gestational hypertension and pre-eclampsia.

Effects of Industrial Waste Fish Oil Administration on Interleukin-6 (Il-6) Expression at Mice Colon being Induced by Azoxymethane (AOM) and Dextran Sodium Sulphate (DSS)

Colorectal cancer (CRC) is the world’s third most cancer and the second highest mortality rate. The searching for new anti-inflammation substances with less adverse effects than aspirin for chemoprevention and adjuvant chemotherapy of CRC is running. The most notable one is fish oil containing omega 3. Kusmardi, et al. studied that industrial waste fish oil omega-3 level comes close enough to conventional fish oil industry. Study aims to reducing the level IL-6 on mice colon tissue being induced CRC using AOM/DSS by fish oil administration. Thirty male Swiss Webster mice are grouped into six treatments: positive control (aspirin), negative control (physiological saline), normal, high dose (fish oil 6mg/kgBW), medium dose (fish oil 3mg/kgBW), dan solvent control (corn oil). Colon tissue was stained using anti IL-6 antibody. Ten photos per slide were taken by microscope (400x), analyzed for the IL-6 expression by ImageJ®, and quantified for H-score. Data was analyzed using SPSS 24.0 (CI 95%) and p-value <0.05 is consider significant. Data are not normally distributed with median of 161.64 (119.4-260.67). Kruskal-Wallis test is significant in addition with Mann-Whitney test shows only high dose group has significant difference to negative control (p=0.008), medium dose (p=0.016) dan and solvent control (p=0.008). No significant difference reported between high dose and positive control group (p=0.69). High dose industrial waste fish oil can lower IL-6 expression in mice colon tissue induced CRC using AOM/DSS.

Kinetics of DNA Repair Under Chronic Irradiation at Low and Medium Dose Rates in Repair Proficient and Repair Compromised Normal Fibroblasts

We present time and dose dependencies for the formation of 53BP1 and γH2AX DNA damage repair foci after chronic radiation exposure at dose rates of 140, 250 and 450 mGy/day from 3 to 96 h, in human and mouse repair proficient and ATM or DNA-PK deficient repair compromised cell models. We describe the time/dose-response curves using a mathematical equation which contains a linear component for the induction of DNA damage repair foci after irradiation, and an exponential component for their resolution. We show that under conditions of chronic irradiation at low and medium dose rates, the processes of DNA double-strand breaks (DSBs) induction and repair establish an equilibrium, which in repair proficient cells manifests as a plateau-shaped dose-response where the plateau is reached within the first 24 h postirradiation, and its height is proportionate to the radiation dose rate. In contrast, in repair compromised cells, where the rate of repair may be exceeded by the DSB induction rate, DNA damage accumulates with time of exposure and total absorbed dose. In addition, we discuss the biological meaning of the observed dependencies by presenting the frequency of micronuclei formation under the same irradiation conditions as a marker of radiation-induced genomic instability. We believe that the data and analysis presented here shed light on the kinetics of DNA repair under chronic radiation and are useful for future studies in the low-to-medium dose rate range.

Tangnaikang Alleviates Hyperglycemia and Improves Gut Microbiota in Diabetic Mice

Dysregulation of gut microbiota contributes to the development of type 2 diabetes. To investigate the antidiabetic effect of Tangnaikang and its regulation of gut microbiota in diabetic KKAy mice, a type 2 diabetes mouse model was established by feeding KKAy mice with a high-fat diet (HFD) for 2 weeks. The diabetic KKAy mice were treated with vehicle, Acarbose, or different doses of Tangnaikang once a day for 8 weeks. The fasting plasma glucose (FPG) levels and bodyweights were measured weekly. The fecal and blood samples were collected 8 weeks after treatment. The 16s rRNA sequencing and bioinformatics analysis were conducted to explore the effects of Tangnaikang treatment on the richness, diversity, and relative abundance of gut microbiota. Compared with other treatments, high-dose Tangnaikang (4.68 g/kg) significantly reduced FPG levels while elevating bodyweights in model mice. Compared with saline treatment, different doses of Tangnaikang significantly increased gut microbial species richness and diversity. Linear discriminant analysis effect size identified potential bacterial biomarkers associated with Tangnaikang treatment. Relative abundance analysis revealed that Tangnaikang treatment modulated the abundance of gut bacteria at the class and genus levels, such as Bacilli, Lactobacillus, and Alistipes. The principal component analysis demonstrated that, compared with the samples of the high-dose group, the samples of medium-dose and low-dose groups were closer to those of the model group. Tangnaikang alleviated hyperglycemia and improved the composition and abundance of gut microbiota in diabetic KKAy mice.

Continuous Intake of High Doses of Piper guineense (Ashanti pepper) Aqueous Seed Extract Impairs Renal Function in Wistar Rats

BACKGROUND: Piper guineense seed is a well known spice consumed in many parts of West Africa as a result of its nutritional and medicinal properties. METHODS: Twenty Wistar rats were divided into four groups of five per group. The phytochemical analyses was done; different concentration of aqueous seed extract of Piper guineense was administered for 21 days to three experimental groups, Group 2 (25 mg/kg), Group 3 (50 mg/kg), Group 4 (100 mg/kg), while group 1 were given only rat feed and water. RESULTS: The investigation revealed that in low and medium dose groups, creatinine (62.3±7.3 to 51.1±4.5 and 51.1±8.1 respectively) and urea (6.6±1.3 to 5.2±0.8 and 4.8±1.0) levels decreased significantly while in high dose group, creatinine (62.3±7.3 to 66.9±11.0) and urea (6.6±1.3 to 7.0±0.8) increased significantly. There was a dose dependent increase in the serum electrolyte (sodium, potassium, chlorine and bicarbonate). Only bicarbonate (19.1±0.8 to 24.3±1.3) and chloride (102.4±3.8 to 107.0±1.6) had significant increase in their values. The histological study showed that at a low (25mg/kg) and medium dose (50mg/kg) of aqueous seed extract of Piper guineense the normal cyto-architecture of the kidney was maintained while in high dose group (100mg/kg) normal cyto-architecture of the kidney was distorted. CONCLUSION: The result obtained suggests that Piper guineense seed may not be harmful at a moderate dose; but high doses could be toxic. Caution should be taken on the quantity of Piper guineense seed consumed.

Comparison of the Efficacy and Safety of Different Doses of Linaclotide for Patients with Chronic Constipation: A Meta-Analysis and Bayesian Analysis

Background. It is ambiguous whether a higher dose of linaclotide provides higher efficacy for chronic constipation (CC) patients. The meta-analysis aimed to assess the efficacy and safety of linaclotide doses ranging from 62.5 μg to 600 μg for CC patients. Methods. A comprehensive search was conducted, and STATA16 software was used for data analysis. Results. Seven studies with 4,107 patients were eligible. A significantly enhanced number of completely spontaneous bowel movement (CSBM) responders were found in the extremely low-dose group (OR: 2.94; 95% CI: 1.98–4.34; p < 0.001 ), the low-dose group (OR: 3.24; 95% CI: 2.44–4.31; p < 0.001 ), the medium-dose group (OR: 3.08; 95% CI: 1.46–6.50; p = 0.003 ), and high-dose group (OR: 4.79; 95% CI: 3.04–7.54; p < 0.001 ). Bayesian analysis showed the high-dose group obtained the maximum CSBM responder rate (OR: 4.94; 95% credible interval (CrI): 3.22–7.79; probability rank = 0.87) indirectly compared with extremely low-dose, low-dose, and medium-dose groups. However, no significant difference presented in the CSBM responder rate by pairwise comparisons of the different dose groups. Additionally, no more any adverse events occurred in the higher linaclotide dose group (RR: 0.91; 95% CrI: 0.60–1.38) indirectly compared with other dose groups. Conclusions. High dose of linaclotide could be more effective and safer for CC patients, which need more trials to confirm in the future.

Effect of Nalbuphine Combined With Intravenous Propofol for Anesthesia During Intestinal Endoscopic Submucosal Dissection in the Elderly

Objective: To investigate the effects of different doses of nalbuphine combined with an intravenous propofol pump for anesthesia during intestinal endoscopic submucosal dissection (ESD) in the elderly.Methods: A total of 85 elderly patients attending the Hanchuan People's Hospital from January 2016 to January 2018 were divided into low, medium, and high dose groups according to the intravenous dosing of nalbuphine given with a continuous propofol pump.The heart rate (HR), mean arterial pressure (MAP), and blood oxygen saturation (SaO2) were evaluated at five different time points (T1-T2).The levels of norepinephrine (NE), cortisol and blood glucose were intervals recorded. The occurrence of adverse reactions, hospitalization days, visual analogue scale (VAS) score, Ramsay sedation, and wake score after waking from anesthesia were assessed. Neurocognitive function was assessed at discharge and after surgery using the Montreal Cognitive Assessment (MoCA). Results: MR, MAP and SaO2 decreased significantly at T0-T4 in tested groups. The levels of NE, Cor, and Glu were significantly increased in three groups at T1-T3 and decreased among the medium-dose group. There was no statistically significant difference between the three groups in the total duration of anesthesia and the operative duration. The medium-dose group was performing significantly better than the low and high dose groups in clinical indicators. The postoperative VAS and Ramsay scores were higher in the low dose group (P＜0.05). There was a significant difference in neurocognitive function scores and no significant differences in postoperative anesthesia satisfaction and hospitalization days were observed amongst the three groups (P>0.05).Conclusions: The use of nalbuphine (0.1 mg/kg) combined with propofol for anesthesia during intestinal ESD in the elderly can shorten recovery times and reduce the incidence of postoperative adverse events and neurocognitive disorders.

Effects of Caffeine Consumption on Autologous Full-Thickness Skin Graft Healing in an Animal Model

Background There exists contradictory evidence that states both the beneficial and deleterious effects of caffeine on wound healing. The general population might unknowingly consume caffeine that negatively affects wound healing. The main objective of this study is to investigate the effect of daily caffeine consumption on wound healing, specifically full-thickness skin graft (FTSG). Methods Forty Sprague-Dawley rats were randomized into four groups of equal size: control-dose (CD), low-dose (LD), medium-dose (MD), and high-dose (HD) caffeine groups. After autologous FTSG, all subjects in the intervention group were given daily pure caffeine gavage. The FTSG was explanted 7 days posttransplant. The graft viability, secondary contraction, and adherence were evaluated macroscopically, while fibroblast and collagen deposition was analyzed microscopically with hematoxylin eosin stain. Results The least graft viability (72.8 ± 20.7%, clinical wound assessment scale [CWAS] 2.4), highest secondary contraction (11.4 ± 10.5%), and fibroblast count (331.8 ± 88.6 cells/5 high power fields) were observed in the MD group. More collagen synthesis was observed in subjects who consumed caffeine. The level of secondary contraction, fibroblast count as well as graft viability and collagen synthesis were positively correlated. Conclusions Daily consumption of caffeine impairs graft viability when given in medium dose and increases collagen synthesis, irrespective of dosage. This study was in experimental rats; the results are not directly translatable to humans.