Moderate-dose Group Research Articles

Subchronic oral toxicity assessment of Ayurvedic herbo-metallic formulation Mahalaxmi Vilas Rasa in Wistar rats

Abstract BACKGROUND: Mahalaxmi Vilas (MV) Rasa, a revered Ayurvedic herbo-metallic formulation, holds historical significance for its therapeutic potential. In light of its traditional use, a rigorous evaluation of its safety profile in Wistar rats is imperative for establishing its evidence-based safety. This study aims to contribute valuable insights to the scientific community and healthcare practitioners, facilitating informed decision-making regarding the integration of MV into contemporary medical practices. The findings hold relevance for advancing our understanding of Ayurvedic formulations in the context of safety and efficacy, fostering a bridge between traditional wisdom and modern scientific scrutiny. METHODS: In the present study, a total of 24 Wistar rats were randomly divided into four groups as one control vehicle and three dose levels of the test drug MV Rasa. The test drug was made into suspension in a vehicle (honey-to-water ratio, 2:3) and administered orally once a day for 90 consecutive days in three dose levels (51.36, 205.44, and 513.6 mg/kg). Clinical observations, body weight changes, and food and water consumption were noted during the study. Then, on the 91st day, rats were sacrificed humanely, and parameters, such as hematological, biochemical, relative organ weight, and histopathological changes, were studied. RESULTS: There was a significant decrease in water intake in high-dose group rats (513.6mg/kg) in the weeks 1, 3, and 4, as compared with control group rats, the observed effect was not treatment related. In addition, MV (51.36, 205.44, and 513.6 mg/kg) produced no significant alterations in any of the hematological and biochemical parameters, except for a significant increase in direct bilirubin in the moderate dose group (205.44 mg/kg). However, no considerable cellular changes were found in the organs analyzed. CONCLUSION: MV had no toxic effect in Wistar rats during this repeated dose oral toxicity (90 days) study, even at 10 times the therapeutic dose (513.6 mg/kg). This was evidenced by their normal behavioral, hematological, biochemical, and histopathological examinations.

Dose-dependent increase in risk of bleeding and bleeding complications in relation to SSRI use at delivery

IntroductionDepression during pregnancy is a severe state that increases the risk of suicide, as well as adverse newborn outcomes. Selective serotonin re-uptake inhibitors (SSRIs) are effective for the treatment of depression, but increase the risk of bleeding complications at delivery. Knowledge on the dose dependency of this association is lacking. MethodsA hospital-based cohort study of all women who gave birth at Karolinska University Hospital in Stockholm over the 5-year period from 2007 to 2011, with or without SSRI use, was undertaken. In total, 334 women who delivered vaginally and were exposed to SSRIs at delivery were identified. All other women who delivered vaginally formed the control group (n = 31,929). The electronic maternal health records of the 334 SSRI users were scrutinized, and the women were categorized into two groups: moderate (n = 246) or high (n = 88) SSRI dose at delivery. The main outcome was bleeding complications at delivery in relation to SSRI dose. ResultsA dose-dependent increase in the rate of postpartum haemorrhage (≥1000 ml) was found, affecting 8.4 %, 14.6 % and 23.9 % (p ≤ 0.001) of women in the control group, the moderate-dose group and the high-dose group, respectively. In addition, a dose-dependent increase in the rate of postpartum anaemia was found, affecting 7.0 %, 9.3 % and 15.9 % (p = 0.001) of women in the control group, the moderate-dose group and the high-dose group, respectively. Mean blood loss of 406 ml, 483 ml and 482 ml (p ≤ 0.001) was found in the control group, the moderate-dose group and the high-dose group, respectively. Women exposed to SSRIs delivered earlier, but did not have higher prevalence of pre-eclampsia compared with the control group. ConclusionsThe dose-dependent relationship between SSRIs and bleeding complications may be clinically useful in the management of this vulnerable group of women.

An investigation into the potential therapeutic effects of the Qigu Zhushui decoction on mouse models of malignant ascites.

To determine whether or not a decoction made from Qigu Zhushui has a suppressive impact on malignant ascites in mice. Malignant ascites are one of the common complications of advanced malignant tumors. Patients with malignant ascites typically have a poor prognosis, with only 12 to 20 weeks of survival. Currently, the standard treatments for malignant ascites are systemic chemotherapy, which is ineffective in eradicating the disease and is associated with issues such as safety, short duration of sustained high-level drug concentration in localised regions, and drug resistance. To clarify the effect of Qigu Zhushui decoction on inhibiting malignant ascites in mice and provide the experimental basis for further research. The ascites model of liver cancer in mice was established by intraperitoneal injection of the H22-H8D8 cell line of liver cancer. ELISA detected the content of CEA, VEGF and TNF-α in ascites. Qigu Zhushui decoction combined with cisplatin group and Qigu Zhushui decoction high-dose group could significantly reduce the weight, abdominal circumference and ascites volume of mice, and their survival days and survival rate were also greatly improved; The levels of CEA and VEGF in the combination group decreased significantly, while the level of TNF-α increased; The level of TNF-a in the high dose group of Qigu Zhushui decoction was significantly increased, while the level of CEA and VEGF in the moderate dose group was decreased. Qigu Zhushui decoction can reduce the malignant ascites in mice, and the combination of Qigu Zhushui decoction and cisplatin has a significant anti-malignant ascites effect, which can significantly prolong the survival time and improve the survival rate.

Effect of Exercise Training on Lipoprotein Subclass Particle Concentrations and Sizes in Older Women: Results from a Randomized Controlled Trial.

Evidence suggests that lipoprotein subclass particles are critical markers of cardiovascular disease (CVD) risk. Older women have increased CVD risk related to age. The purpose of this study was to determine whether low and moderate doses of exercise influence lipoprotein subclasses. Women (60-75 years) were randomized into groups for 16 weeks of moderate-intensity exercise training at a low or moderate dose (33.6 and 58.8 kJ/kg body weight weekly, respectively). Lipoprotein subclasses were determined by nuclear magnetic resonance spectroscopy before and after the training. The average weekly exercise duration was 109 and 164 min, for low- and moderate-dose groups, respectively. In the low-dose group, high-density lipoprotein particle (HDL-P) concentration decreased (Δ = -1.9 ± 3.1 µmol/L, mean ± SD, p = 0.002) and mean HDL-P size increased (Δ = 0.1 ± 0.3 nm, p = 0.028). In the moderate-dose group, mean HDL-P size (Δ = 0.1 ± 0.2 nm; p = 0.024) and low-density lipoprotein particle size increased (Δ = 0.4 ± 3.9 nm; p = 0.007). Baseline body mass index, peak oxygen consumption and age were associated with changes in a few lipoprotein subclasses. In this sample of inactive older women, moderate-intensity exercise training at a dose equivalent to or even lower than the minimally recommended level by public health agencies induced changes in lipoprotein subclasses in line with reduced CVD risk. However, higher doses are encouraged for greater health benefits.

Examining Potential Modifiers of Human Skin and Plasma Carotenoid Responses in a Randomized Trial of a Carotenoid-Containing Juice Intervention

BackgroundSkin carotenoid measurements are emerging as a valid and reliable indicator of fruit and vegetable intake and carotenoid intake. However, little is known about the extent to which skin carotenoid responsivity to dietary changes differs based on demographic and physiologic characteristics. ObjectivesThis study examined potential effect modifiers of skin carotenoid and plasma carotenoid responses to a carotenoid-rich juice intervention. MethodsWe leveraged data from 2 arms of a 3-site randomized controlled trial of a carotenoid-containing juice intervention (moderate dose = 6 ounces juice, 4 mg total carotenoids/d, high dose = 12 ounces juice, 8 mg total carotenoids/d) (n = 106) to examine effect modification by age, self-categorized race/ethnicity, biological sex, baseline body fat, body mass index, skin melanin, skin hemoglobin, skin hemoglobin saturation, skin coloration, sun exposure, and baseline intake of carotenoids from foods. Skin carotenoid concentrations were assessed using pressure-mediated reflection spectroscopy (Veggie Meter), and plasma carotenoid concentrations were measured using high-performance liquid chromatography. ResultsIn bivariate analyses, among the high-dose group (8 mg/d), those of older age had lower skin carotenoid responsiveness than their younger counterparts, and those with greater hemoglobin saturation and lighter skin had higher skin carotenoid score responsiveness. In the moderate-dose group (4 mg/d), participants from one site had greater plasma carotenoid responsiveness than those from other sites. In multivariate analyses, participants with higher baseline skin carotenoids had smaller skin carotenoid responses to both moderate and high doses. ConclusionsChanges in skin carotenoid scores in response to interventions to increase fruit and vegetable intake should be interpreted in the context of baseline skin carotenoid scores, but other variables (e.g., self-categorized race/ethnicity, biological sex, baseline body fat, body mass index, skin melanin, and sun exposure) do not significantly modify the effect of carotenoid intake on changes in skin carotenoid scores.This trial was registered at clinicaltrials.gov as NCT04056624.

Lead Exposure Assessment and Its Impact on the Structural Organization and Morphological Peculiarities of Rat Ovaries.

Lead is known to be highly toxic to humans, causing various disorders infetal development. An experiment was conducted to examine the effects of lead acetate on the structural organization of female rat ovaries. The study involved 40 non-linear female rats divided into four groups: a control group, a low-dose group, a moderate-dose group, and a high-dose group. The rats were given lead acetate solutions in varying doses for 30 days, and their ovarian tissue was examined using light microscopy.The results showed that increasing doses of lead acetate led to morphological changes in the cortex and medulla of the rat ovaries. The changes were characterized by a decrease in ovarian mass, alterations in the thickness of the tunica albuginea (protein envelope), and a reduction in the number of follicles. Light microscopy revealed that exposure to lead acetate resulted in a significant decrease in the number of follicles in all experimental groups, with the high-dose group experiencing the most significant decrease.These findings suggest that lead acetate has a dose-dependent negative impact on the morphology and function of female rat ovaries. Further studies are needed to investigate the potential impact of lead on human ovarian tissue.

Dingkun Pill modulate ovarian function in chemotherapy-induced premature ovarian insufficiency mice by regulating PTEN/PI3K/AKT/FOXO3a signaling pathway

Ethnopharmacological relevanceDingkun Pill (DKP) is a traditional Chinese medicine that has been shown to have beneficial effects on reproductive function. However, the specific mechanism underlying its effect on POI is not well understood. Aim of the studyTo investigate the effect of different doses of Dingkun Pill on ovarian function in cyclophosphamide (CTX)-induced premature ovarian insufficiency (POI) mice and to explore its molecular mechanism through PTEN/PI3K/AKT/FOXO3a signaling pathway. This study will provide valuable insights into the potential clinical application of Dingkun Pill for the treatment of POI. Materials and methodsFifty female ICR mice were randomly divided into normal control (NC) group, model control (MC) group, and Dingkun Pill low, medium, high dose (DKP-L, M, H) groups. Mice were injected with CTX to construct the POI model. Mice in the DKP-L, M, and H groups were given 0.9 g/kg, 1.8 g/kg, and 3.6 g/kg of Dingkun Pill suspension for 21 days, respectively. Mice in the NC and MC groups were given the same amount of normal saline by gavage. Changes in body weight, estrous cycle and gonadal index were observed in each group of mice. Serum levels of FSH, LH, E2 and AMH were detected by ELISA. Hematoxylin-eosin (HE) staining observed the changes of ovarian pathological morphology and follicle counts at all levels. qRT-PCR was used to measure the levels of the PTEN and FOXO3a genes in ovarian tissue. The expression of PTEN/PI3K/AKT/FOXO3a signaling pathway related proteins were detected by Western-blot and immunohistochemistry (IHC). ResultsIn POI mice, Dingkun Pill increased body weight, promoted the recovery of estrous cycle, increased ovarian index, and improved pathological morphology of the ovaries. The FSH level decreased in the medium dose group (P < 0.05), the LH level reduced significantly in the medium and high dose groups (P < 0.01), and the E2 level in the high dose group increased (P < 0.05). There was no significant difference in AMH levels across all dose groups. The number of growing follicles improved at all levels in the low and medium dose groups, but declined significantly in the high dose group. However, the number of corpus luteum increased significantly in the high dose group (P < 0.001), and the atretic follicles in the three dose groups decreased. Results from qRT-PCR, Western-blot and IHC showed that the moderate dose of Dingkun Pill suppressed the levels of the p-PI3K and p-AKT proteins by upregulating the expression of PTEN in the ovarian tissues of POI mice, thereby inhibiting the expression of the key protein p-FOXO3a. However, the inhibitory effect of the higher dose may be less than that of the lower and intermediate dose groups. ConclusionsThe Dingkun Pill modulated hormonal levels, promoted follicle growth and induced ovulation in mice with CTX-induced POI, with better results in the low and moderate dose groups. Its mechanism may be related to the regulation of the PTEN/PI3K/AKT/FOXO3a signaling pathway.

Effects of different doses of exercise and diet-induced weight loss on beta-cell function in type 2 diabetes (DOSE-EX): a randomized clinical trial

Diet-induced weight loss is associated with improved beta-cell function in people with type 2 diabetes (T2D) with remaining secretory capacity. It is unknown if adding exercise to diet-induced weight loss improves beta-cell function and if exercise volume is important for improving beta-cell function in this context. Here, we carried out a four-armed randomized trial with a total of 82 persons (35% females, mean age (s.d.) of 58.2 years (9.8)) with newly diagnosed T2D (<7 years). Participants were randomly allocated to standard care (n = 20), calorie restriction (25% energy reduction; n = 21), calorie restriction and exercise three times per week (n = 20), or calorie restriction and exercise six times per week (n = 21) for 16 weeks. The primary outcome was beta-cell function as indicated by the late-phase disposition index (insulin secretion multiplied by insulin sensitivity) at steady-state hyperglycemia during a hyperglycemic clamp. Secondary outcomes included glucose-stimulated insulin secretion and sensitivity as well as the disposition, insulin sensitivity, and secretion indices derived from a liquid mixed meal tolerance test. We show that the late-phase disposition index during the clamp increases more in all three intervention groups than in standard care (diet control group, 58%; 95% confidence interval (CI), 16 to 116; moderate exercise dose group, 105%; 95% CI, 49 to 182; high exercise dose group, 137%; 95% CI, 73 to 225) and follows a linear dose–response relationship (P > 0.001 for trend). We report three serious adverse events (two in the control group and one in the diet control group), as well as adverse events in two participants in the diet control group, and five participants each in the moderate and high exercise dose groups. Overall, adding an exercise intervention to diet-induced weight loss improves glucose-stimulated beta-cell function in people with newly diagnosed T2D in an exercise dose-dependent manner (NCT03769883).

Cell cycle dysregulation on prenatal and postnatal arsenic exposure in skin of Wistar rat neonates

This study explores the effects of prenatal and postnatal (until weaning period) arsenic exposure given via pregnant females on Wistar rat neonates. Pregnant female rats were divided in four groups – control, low dose, moderate dose and high dose groups of sodium arsenite exposure during gestation and weaning period. Half of the neonates were sacrificed at day 1 of birth and other half at day 21 of birth. Cell cycle analysis in epidermal keratinocytes using flowcytometer revealed that there was a consistent increase in number of cells in G2/M phase from 0.04% in control group to 0.88%, 1.59% and 2.77% in low, moderate and high dose groups respectively for neonates sacrificed at day-1. Whereas, the increase in number of cells with increasing doses in G2/M phase of neonates sacrificed at day-21 was from 3.44% to 5.1%, 6.82%, and 9.17%. At postnatal day 21, mRNA expression of Cyclin A and B1, p53, Caspases 3, 7 and 9, and Bax were found to be up-regulated. Whereas that of Cyclin E, CDK 1 and 2 and Bcl2 were down regulated consistently in skin tissues of arsenic exposed groups.

The Anti-hyperuricemia and Anti-inflammatory Effects of Atractylodes Macrocephala in Hyperuricemia and Gouty Arthritis Rat Models.

Atractylodes macrocephala is a traditional Chinese medicine with a variety of pharmacological activities. This study aimed to evaluate its anti-hyperuricemia and antiinflammatory effects on gout, and to preliminarily explore its mechanism. The hyperuricemia rat model was established by intraperitoneal injection of oteracil potassium and intragastric gavage of yeast powder solution. And the acute gouty arthritis (GA) model was established by injecting monosodium urate (MSU) suspension. In the study of the antihyperuricemia effect of Atractylodes macrocephala, the healthy male Sprague-Dawley rats were randomly divided into the blank group, hyperuricemia group allopurinol group as well as low, moderate and high dose groups of Atractylodes macrocephala decoction (N=8 rats in each group). Serum, liver and kidney tissue samples were collected from each group. Serum uric acid (UA), adenosine deaminase (ADA) and xanthine oxidase (XOD) levels in each group were detected by enzyme-linked immunosorbent assay (ELISA). Protein levels of ADA and XOD in liver tissues were detected by Western blot, and renal histological changes were observed by Hematoxylin-eosin (H&E) and Masson staining. In order to investigate the anti-inflammatory effect of Atractylodes macrocephala, the healthy male Sprague-Dawley rats were randomly divided into the blank group, GA group, colchicine group, high, moderate and low dose groups of Atractylodes macrocephala decoction (N=8 rats in each group), and serum and synovial tissue of each group were collected. Then the level of serum interleukin (IL)-1β and tumor necrosis factor (TNF)-α was observed by ELISA, and the histological changes of synovial tissue were observed by H&E staining. Besides, the expression of adenosine monophosphate- activated protein kinase (AMPK) /silent information regulator (SIRT) 1/ nuclear factor kappa B (NF-κB) protein in synovial tissue was observed by Western blot and immunohistochemistry. The markers of M1 and M2 macrophages, inducible nitric oxide synthase (iNOS) and arginase-1 (ARG1) were observed by Western blot and immunofluorescence. Atractylodes macrocephala could reduce the production of UA by inhibiting the level of ADA and XOD, and could improve renal injury and fibrosis. In addition, Atractylodes macrophages could reduce the levels of IL-1β and TNF-α, activate AMPK/SIRT1 signaling pathway, and inhibit the activation of NF-κB and the polarization of macrophages to a pro-inflammatory phenotype. Atractylodes macrocephala shows good anti-hyperuricemic and anti-inflammatory effects, and its anti-inflammation pharmacological activity may be related to the inhibition of M1 macrophage polarization and NF-κB activation through activating AMPK/SIRT1.

Effects of High-Intensity Interval Training on Executive Functions in College Students: Evidence from Different Doses

Different doses of high-intensity interval training (HIIT) may affect individuals' executive functions (EF). In this study, low-dose HIIT and moderate-dose HIIT were used to explore different doses of HIIT in terms of the impact on the EF of college students. All the participants were randomly divided into three groups. One group was not assigned any HIIT, which was called the control group. One group was assigned one session of HIIT/week, which was called the low-dose group. The last group was assigned wo sessions of HIIT/week, which was called the moderate-dose group. All groups were subjected to EF measurements. The first measurement comprised an EF a baseline measurement (Time 1) before the experiment began; the second measurement was taken (Time 2) after 6 weeks; the third measurement was taken (Time 3) after 12 weeks. Time 1: We found that there was no significant difference in EF among the groups (p > 0.05). Time 2: The moderate-dose group and low-dose group improved in terms of EF. However, the improvement effect was different, and the improvement effect of the moderate-dose group EF was better than that of the low-dose group. The second measurement, EF was better for all exercise groups than for the control group. Inhibition test (reaction time: 3.97-8.24%, p < 0.05, effect size: 0.413); cognitive flexibility (accuracy: 6.66-7.32%, p < 0.05, effect size: 0.203; reaction time: 5.55-7.49%, p < 0.05, effect size: 0.521); working memory (accuracy: 4.05-4.69%, p < 0.05, effect size: 0.515; reaction time: 2.73-5.42%, p < 0.05, effect size: 0.430). Time 3: the moderate-dose group and low-dose group showed a downward trend in terms of EF. Low-dose HIIT and moderate-dose HIIT improved the EF in college students, but moderate-dose HIIT was better. This study suggests that moderate-dose HIIT should be adopted to improve the EF in college students.

Long-term dietary nitrate supplementation slows the progression of established atherosclerosis in ApoE−/− mice fed a high fat diet

Background and aimsAtherosclerosis is associated with a reduction in the bioavailability and/or bioactivity of endogenous nitric oxide (NO). Dietary nitrate has been proposed as an alternate source when endogenous NO production is reduced. Our previous study demonstrated a protective effect of dietary nitrate on the development of atherosclerosis in the apoE−/− mouse model. However most patients do not present clinically until well after the disease is established. The aims of this study were to determine whether chronic dietary nitrate supplementation can prevent or reverse the progression of atherosclerosis after disease is already established, as well as to explore the underlying mechanism of these cardiovascular protective effects.Methods60 apoE−/− mice were given a high fat diet (HFD) for 12 weeks to allow for the development of atherosclerosis. The mice were then randomized to (i) control group (HFD + 1 mmol/kg/day NaCl), (ii) moderate-dose group (HFD +1 mmol/kg/day NaNO3), or (iii) high-dose group (HFD + 10 mmol/kg/day NaNO3) (20/group) for a further 12 weeks. A group of apoE−/− mice (n = 20) consumed a normal laboratory chow diet for 24 weeks and were included as a reference group.ResultsLong-term supplementation with high dose nitrate resulted in ~ 50% reduction in plaque lesion area. Collagen expression and smooth muscle accumulation were increased, and lipid deposition and macrophage accumulation were reduced within atherosclerotic plaques of mice supplemented with high dose nitrate. These changes were associated with an increase in nitrite reductase as well as activation of the endogenous eNOS-NO pathway.ConclusionLong-term high dose nitrate significantly attenuated the progression of established atherosclerosis in the apoE−/− mice fed a HFD. This appears to be mediated in part through a XOR-dependent reduction of nitrate to NO, as well as enhanced eNOS activation via increased Akt and eNOS phosphorylation.

Dose-Response Relationship between Head and Neck Radiation and Damages to Gustatory Cells in Mice.

To investigate the dose-response relationship between radiation to the head and neck regions and damage observed in mice gustatory cells. A total number of 45 mice (C57BL/6) (aged 8-12 weeks) were enrolled in this study. The head and neck regions of the mice were irradiated at doses of 8 Gy (low-dose group, n = 15), 16 Gy (moderate-dose group, n = 15), and 24 Gy (high-dose group, n = 15). Each time, 3 mice from each group were sacrificed before radiation and then 2-day, 4-day, 7-day, and 14-day post the irradiation, respectively. The immune-histochemical staining method was employed to obtain gustatory papilla tissues and mark gustatory cells. Careful calculation of the numbers of proliferative cells, taste buds, and type II gustatory cells was conducted. A decrease in the number of Ki-67-marked proliferative cells was noted at 2 days postirradiation (DPI), and the number of cells was recovered to the normal level at 4-DPI in each group. The number of Ki-67-marked proliferative cells was hypercompensation (significantly higher than normal) in the moderate-dose and high-dose groups at 7-DPI and insufficient compensation (significantly lower than normal) in the high-dose group at 14-DPI. There was a significant reduction of taste buds and type II gustatory cells at 2-DPI and is lowest at 4-DPI in the moderate-dose and high-dose groups, while little change was observed in the low-dose group. Damages to Gustatory Cells after head and neck radiation were dose-related and compensation occurred in 14-DPI and may be insufficient when overdosed.

Reflection Spectroscopy-Assessed Skin Carotenoids Are Sensitive to Change in Carotenoid Intake in a 6-Week Randomized Controlled Feeding Trial in a Racially/Ethnically Diverse Sample

BackgroundReflection spectroscopy, utilized by the Veggie Meter, is a less-expensive, noninvasive method to quantify skin carotenoids and is a valid approximation of fruit and vegetable (FV) intake. However, it is unknown to what degree Veggie Meter–assessed skin carotenoid score change is responsive to changes in carotenoid intake. ObjectivesThis study aimed to evaluate Veggie Meter–assessed skin carotenoid score response in a 6-wk randomized controlled trial of a carotenoid-containing juice to determine whether the Veggie Meter can be used to detect nutritionally relevant changes in carotenoid intake; and to compare skin and plasma carotenoid responses with the 6-wk trial. MethodsIn this 6-wk trial, participants (n = 162) who self-identified as one of 4 US racial/ethnic groups (25% Black, 25% Asian, 27% non-Hispanic White, 23% Hispanic) were randomized to a control group, receiving negligible carotenoids (177 mL apple juice/d), moderate-dose group, receiving 4 mg total carotenoids/d (177 mL orange–carrot juice/d), or high-dose group, receiving 8 mg total carotenoids/d (355 mL orange–carrot juice/d). Skin carotenoid score and plasma total carotenoid concentrations (α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein, zeaxanthin) were assessed at baseline, 3 wk, and 6 wk (n = 158 completed the trial). Repeated measures linear models were used to examine skin and plasma carotenoids over time and between groups. ResultsAt 6 wk, participants in the high-dose and moderate-dose groups had significantly higher mean skin carotenoid scores [414.0 (SD = 100.6) and 369.7 (SD = 100.3), respectively] compared with those in the control group [305.2 (100.5)]. In the high-dose group, there was a 42% change in skin carotenoids from baseline (mean = 290.4) to a 6-wk follow-up (increase of 123, 123/290 = 42.4%). There was a 61% change in the plasma carotenoids in the high-dose group. ConclusionsThe Veggie Meter is sensitive to increases in daily carotenoid intake in diverse racial/ethnic groups over 6 wk. Clinical Trials Registry numberThis trial was registered at clinicaltrials.gov as ID: NCT04056624. Study URL: https://clinicaltrials.gov/ct2/show/NCT04056624

The Effect of Ethanolic Extract of Justicia Secunda on Kidney Function in Female Wistar Rats

Purpose: The kidneys serve as the excretory organ of the body. The assessment of serum creatinine, urea, and electrolytes (Na+, K+, HCO3-, Cl-) are crucial and sensitive biochemical markers that are usually involved in the diagnosis of renal impairments (Agbasi et al. 2010; Tietz, 2008; Yakubu et al. 2003).&#x0D; Methodology: Thirty-six animals were grouped into 6, with 6 rats in each group. The animals were housed at room temperature in metal cages. Animals in each group had access to clean water and commercial standard rodent pellets. Group 1 (control group) received distilled water, Groups 2-6 were treated orally with low, middle, and high doses of ethanolic extract of Justicia secunda leaves daily for 42 days.&#x0D; Findings: A significant increase in the level of urea concentration was observed compared to the control. From the present study, Na+, K+, Cl-, and HCO3 increased significantly in the moderate and high dose groups.&#x0D; Unique contribution to theory, policy and practice: In conclusion, this study indicates that ethanolic extract of Justicia secunda increased the serum level of urea, creatinine, and electrolytes.

EFFECT OF ORAL ADMINISTRATION OF Emilia coccinea LEAF EXTRACT ON ETHANOL INDUCED GASTRIC DAMAGE IN ADULT WISTAR RATS

The effect of the aqueous extract of Emilia coccinea leaves on ethanol- induced gastric damage was investigated on adult wistar rats for four weeks. 30 experimental animals weighing between 180g and 250g were used and they were divided into five groups of six animals each; groups A,B,C,D and E. Group A animals served as negative control, group B animals served as the positive control and they were given ethanol only, group C to E animals were administered with 1ml/kg of ethanol each to inducegastric erosion and they were later administered with the aqueous extract of Emilia coccinea leaves orally for four weeks. Group C animals were the low dose group and they were administered 200mg/kg body weight of the extract; Group D animals were the moderate dose group and were administered 400mg/kg body weight of the extract while Group E was the high dose group given 600mg/kg body weight of the extract.The animals were sacrificed after 4 weeks and the stomach tissue was harvested fortissue processing and histological observations.The experiment showed that the aqueous extract had ameliorative effects on ethanolinduced gastric damage in a dose- dependent- manner in the experimental animals.

Initial statin dose after myocardial infarction and long-term cardiovascular outcomes.

Effective statin therapy is a cornerstone of secondary prevention after myocardial infarction (MI). Real-life statin dosing is nevertheless suboptimal and largely determined early after MI. We studied long-term outcome impact of initial statin dose after MI. Consecutive MI patients treated in Finland who used statins early after index event were retrospectively studied (N=72401; 67% men; mean age 68 years) using national registries. High-dose statin therapy was used by 26.3%, moderate dose by 69.2%, and low dose by 4.5%. Differences in baseline features, comorbidities, revascularisation, and usage of other evidence-based medications were adjusted for with multivariable regression. The primary outcome was major adverse cardiovascular or cerebrovascular event (MACCE) within 10 years. Median follow-up was 4.9 years. MACCE was less frequent in high-dose group compared with moderate dose [adjusted hazard ratio (HR) 0.92; P<0.0001; number needed to treat (NNT) 34.1] and to low dose [adj.HR 0.81; P<0.001; NNT 13.4] as well as in moderate-dose group compared with low dose (adj.HR 0.88; P<0.0001; NNT 23.4). Death (adj.HR 0.87; P<0.0001; NNT 23.6), recurrent MI (adj.sHR 0.91; P=0.0001), and stroke (adj.sHR 0.86; P<0.0001) were less frequent with a high- vs. moderate-dose statin. Higher initial statin dose after MI was associated with better long-term outcomes in subgroups by age, sex, atrial fibrillation, dementia, diabetes, heart failure, revascularisation, prior statin usage, or usage of other evidence-based medications. Higher initial statin dose after MI is dose-dependently associated with better long-term cardiovascular outcomes. These results underline the importance of using a high statin dose early after MI.

Hydroxyurea for secondary stroke prevention in children with sickle cell anemia in Nigeria: a randomized controlled trial

AbstractWe tested the hypothesis that fixed oral moderate-dose hydroxyurea (20 mg/kg per day) for initial treatment of secondary stroke prevention results in an 80% relative risk reduction of stroke or death when compared with fixed oral low-dose hydroxyurea (10 mg/kg per day) in a phase 3 double-blind, parallel-group, randomized controlled trial in children with sickle cell anemia (SCA) living in Nigeria. A total of 101 participants were randomly allocated to low-dose (n = 49) and moderate-dose (n = 52) hydroxyurea treatment groups. The median participant follow-up was 1.6 years (interquartile range, 1.0-2.3), with a planned minimum follow-up of 3.0 years. A total of 6 recurrent strokes and 2 deaths vs 5 recurrent strokes and 3 deaths occurred in the low- and moderate-dose groups, respectively. The incidence rate ratio (IRR) of the primary outcome measure of stroke or death in the low- and moderate-dose hydroxyurea treatment groups was 0.98 (95% confidence interval [CI], 0.32-3.00; P = .97). The trial was stopped early owing to no clinical difference in the incidence rates of the primary outcome measure. The incidence rates of recurrent strokes were 7.1 and 6.0 per 100 person-years in the low- and moderate-dose groups, respectively, (IRR, 1.18; 95% CI, 0.30-4.88; P = .74). As a measure of adherence to the oral hydroxyurea therapy, the median percent of returned pills was 3.0% and 2.6% in the low- and moderate-dose groups, respectively. No participant had hydroxyurea therapy stopped for myelosuppression. For children with SCA in low-income settings without access to regular blood transfusion therapy, initial low-dose hydroxyurea is a minimum known efficacious dose for secondary stroke prevention.

Degree of exposure to psychotropic medications and mortality in people with bipolar disorder.

To investigate the associations between psychotropic medication dosage and mortality in patients with bipolar disorder. A nationwide cohort of individuals aged ≥15 years who had received a diagnosis of bipolar disorder in 2010 was identified from the Taiwanese national health-care database linked with the mortality registry and followed up for 5 years. The mean defined daily dose (DDD) of mood stabilizers, antipsychotics, antidepressants, and sedative-hypnotics was estimated, and survival analyses were conducted to assess the effects of degree of exposure to psychotropic medications on mortality. A total of 49,298 individuals (29,048 female individuals, 58.92%) with bipolar disorder were included. Compared with individuals without exposure to mood stabilizers, those prescribed mood stabilizers had a decreased overall mortality risk, regardless of exposure dosage. By contrast, compared with a reference group with no exposure to antipsychotics, individuals using antipsychotics had dose-dependent, increased mortality in both overall causes of deaths and deaths due to cardiovascular diseases, with hazard ratios of 1.13 (95% CI: 1.21-1.42) in the low-dose (<0.5 DDD) group, 1.69 (1.51-1.90) in the moderate-dose (0.5-1.5 DDD) group, and 2.08 (1.69-2.57) in the high-dose (>1.5 DDD) group for overall mortality. In sum, mood stabilizers were associated with decreased overall mortality in individuals with bipolar disorder, regardless of the dosage. However, the use of antipsychotics appeared to be associated with a dose-dependent increased mortality risk. Owing to study limitations, precise information on prior use of psychotropic medications, and patient's adherence to medication are not available. Potential adverse effects and benefits should be carefully considered when prescribing psychotropic medications for long-term use in patients with bipolar disorder.

Effects of different doses of methylprednisolone therapy on acute respiratory distress syndrome: results from animal and clinical studies

BackgroundThe optimal dose of glucocorticoids for acute respiratory distress syndrome (ARDS) is uncertain. This study aimed to evaluate the effects of different doses of methylprednisolone on sepsis-induced acute lung injury (ALI) rats and a cohort of moderate and severe ARDS patients.MethodsALI rats, challenged with lipopolysaccharide, were randomly received intraperitoneal injection of normal saline (model group) and different doses of methylprednisolone (0.5, 2, 8 mg/kg, named as low-, moderate- and high-dose group, respectively) for 5 days. The body weight changes of rats, inflammatory factors in bronchoalveolar lavage fluid (BALF), lung wet/dry ratio, histopathological score, and the mRNA expressions of glucocorticoid receptor α (GRα), GRβ and nuclear factor-κB (NF-κB) were measured. Forty moderate and severe ARDS patients were treated with standard of care or plus different doses of methylprednisolone (40, 80, 120 mg/day, named as low-, moderate- and high-dose group, respectively) for 5 days. Clinical outcomes were PaO2/FiO2 ratio and C-reactive protein (CRP) level at day 5, intubation rate, hospital stay, 28-day mortality, and adverse events rate.ResultsIn animal experiment, different doses of methylprednisolone could increase the body weight of rats, and reduce inflammatory factors in BALF and the degree of lung injury compared with model group. The efficacy of methylprednisolone at moderate-dose was better than that at low-dose, but was equivalent to that at high-dose, which was consistent with the differential changes in the mRNA expression of GRα, GRβ and NF-κB. In clinical study, the moderate-dose group was associated with higher PaO2/FiO2 ratio and lower CRP level. No significant difference in other clinical outcomes among groups was detected.ConclusionsThis study showed that the efficacy of methylprednisolone in ARDS treatment was not always dose-dependent due to the differential regulation of related receptors. The moderate-dose of methylprednisolone may be the potential optimal dose for ARDS treatment, which needs to be further verified by larger clinical trials.