Therapeutic Effects Of Different Doses Research Articles

Anti-Cataract Effect of the Traditional Aqueous Extract of Yerba Mate (Ilex paraguariensis A. St.-Hil.): An In Ovo Perspective.

The therapeutic effect of different doses of the traditional aqueous extract of dried leaves of yerba mate (Ilex paraguariensis A. St.-Hil.) was investigated in an experimental cataract model in chicken embryos. LC-MS/MS analysis allowed the identification and quantification of 53 metabolites. In the hydrocortisone-induced cataract model, lenses were examined morphologically after treatment and parameters related to oxidative stress (total antioxidant/oxidant status (TAS/TOS), glutathione (GSH), and malondialdehyde (MDA)) were evaluated. Antiproliferative cell nuclear antigen (PCNA) and caspase-3 H-scores were determined and crystallin alpha A (CRYAA) gene expression in the lenses was measured by RT-PCR. The degree of cataract decreased in all treatment groups. While there was no significant difference in TAS levels compared to the negative control, TOS, GSH, and MDA levels were dose-dependently regulated. Treatment groups other than the high-dose group regulated the decrease in PCNA and the increase in caspase-3. CRYAA gene expression increased significantly only at the lowest dose. YM, which is becoming increasingly popular as a traditional tea, showed a therapeutic effect on hydrocortisone-induced cataracts in chicken embryos at relatively low doses.

RNA-seq combined network pharmacology reveals that Fu-Gan-Wan (FGW) inhibits liver fibrosis via NF-κB/CCL2/CCR2 and lipid peroxidation via Nrf2/HMOX1 signaling pathway

Ethnopharmacological relevanceLiver fibrosis is a serious complication of liver disease characterized by excessive collagen deposition, without effective therapeutic agents in the clinic. Fu-Gan-Wan (FGW) is an empirical formula used for the clinical treatment of hepatitis and cirrhosis. It has been shown to reverse experimental liver fibrosis. However, its corresponding mechanisms remain unclear. Aim of the reviewThis study aimed to elucidate the key pathways and target genes of FGW in attenuating liver fibrosis. Materials and methodsThe therapeutic effects of different doses of FGW on liver fibrosis were investigated using a 2 mL/kg 15% CCl4-induced mouse model. Then, RNA-seq combined with network pharmacology was used to analyze the key biological processes and signaling pathways underlying the anti-liver fibrosis exertion of FGW. These findings were validated in a TGF-β1-induced model of activation and proliferation of mouse hepatic stellate cell line JS-1. Finally, the key signaling pathways and molecular targets were validated using animal tissues, and the effect of FGW on tissue lipid peroxidation was additionally observed. ResultsWe found that 19.5 g/kg FGW significantly down-regulated CCl4-induced elevation of hepatic ALT and AST, decreased collagen deposition, and inhibited the expression of pro-fibrotic factors α-SMA, COL1α1, CTGF, TIMP-1, as well as pro-inflammatory factor TGF-β1. Additionally, FGW at doses of 62.5, 125, and 250 μg/mL dose-dependently blocked JS-1 proliferation, migration, and activation. Furthermore, RNA-seq identified the NF-κB signaling pathway as a key target molecular pathway for FGW against liver fibrosis, and network pharmacology combined with RNA-seq focused on 11 key genes. Significant changes were identified in CCL2 and HMOX1 by tissue RT-PCR, Western blot, and immunohistochemistry. We further demonstrated that FGW significantly attenuated CCl4-induced increases in p-p65, CCL2, CCR2, and HMOX1, while significantly elevating Nrf2. Finally, FGW significantly suppressed the accumulation of lipid peroxidation products MDA and 4-HNE and reconfigured the oxidation-reduction balance, including promoting the increase of antioxidants GPx, GSH, and SOD, and the decrease of peroxidation products ROS and GSSG. ConclusionsThis study demonstrated that FGW exhibits potential in mitigating CCl4-induced hepatic fibrosis, lipid peroxidation, and iron metabolism disorders in mice. This effect may be mediated through the NF-κB/CCL2/CCR2 and Nrf2/HMOX1 pathways.

Zigui-Yichong-Fang protects against cyclophosphamide-induced premature ovarian insufficiency via the SIRT1/Foxo3a pathway

Ethnopharmacological relevanceZigui-Yichong-Fang (ZGYCF) is a traditional Chinese medicine prescription for the treatment of infertility and premature ovarian insufficiency (POI). It is clinically used to regulate hormone levels, improve ovarian reserve and increase pregnancy rate. However, the exact mechanism of action is not yet clear. Aims of the studyThis study aimed to explore the potential impact and mechanism of ZGYCF on POI, and provide a scientific basis for its clinical application. Materials and methodsUHPLC‒MS/MS was used to identify the main compounds of ZGYCF. Female 8-week-old C57BL/6N mice were randomized into four group containing the vehicle control (Veh) group, the cyclophosphamide (CTX) model group, the low-dose ZGYCF (CTX-ZG-L) group and the high-dose ZGYCF (CTX-ZG-H) group. A mouse POI model was induced with a single intraperitoneal injection of CTX, and the therapeutic effects of different doses of ZGYCF on POI were evaluated according to the ovarian weight coefficient, serum AMH, serum E2, ovarian histomorphology and follicle counts. After the dose screening experiment, the CTX-ZG-L group was renamed the CTX-ZG group and subjected to follow-up experiments. RNA-seq was used to explore the mechanism of POI and the therapeutic mechanism of ZGYCF on POI in Veh group, CTX group and CTX-ZG group. The mechanism of action of ZGYCF on POI were determined by measuring serum hormone level, histomorphology, follicle counts, protein expression and acetylation modification in groups of Veh, CTX, CTX-ZG and CTX-ZG-Nam (SIRT1 inhibitor). ResultsA total of 37 compounds in ZGYCF were identified. ZGYCF attenuated the morphological changes in ovarian tissue in POI model mice, increased serum AMH and E2 levels, reduced the damage to primordial follicles and other follicles at all stages, and protected ovarian reserve. RNA-seq results suggested that the genes expression of the PI3K signaling and apoptosis signaling pathways was increased in POI mice, while ZGYCF upregulated SIRT1 gene and the expression of estradiol, apoptosis inhibition and other signaling pathway genes. Immunohistochemical staining, TUNEL staining, Western blot analysis and immunoprecipitation results showed that in CTX group, SIRT1 expression and Foxo3a nuclei localization were decreased, while Ac-Foxo3a, p-AKT, p-Foxo3a and apoptotic markers were upregulated. After administration of ZGYCF, these conditions were reversed, however, after treatment with the SIRT1 inhibitor, the results were opposite to those of ZGYCF. ConclusionsAcetylated Foxo3a plays an important role in the occurrence of POI. ZGYCF improves the ovarian reserve of CTX-induced POI mice by activating SIRT1-mediated deacetylation of Foxo3a, and played a role in the treatment of POI. SIRT1 may be a novel target for ZGYCF to ameliorate POI.

Therapeutic effects of different doses of peroperative intravenous dexmedetomidine for postoperative incision pain in rats

It is essential to minimize postoperative pain immediately after an operation. We compared the effects of different doses of preoperative intravenous dexmedetomidine (DMED) on treating postoperative incision pain in rats. Forty healthy, male, and clean-grade Sprague-Dawley rats were randomly divided into five groups: group C, group B, group D1, group D2, and group D3. The rat hind-limb incision pain model was implemented. The cumulative pain score of each group was determined at two h after surgery. Western blotting was used to determine the spinal cord expression of PKC γ, and high-performance liquid chromatography was used to determine spinal cord glutamate levels. Compared with group C, group B had a significantly greater cumulative pain score and greater spinal cord levels of PKCγ and glutamate. There were significantly lower pain scores and levels of PKCγ and glutamate in groups D2 and D3 than in group D1. Perioperative DMED reduced the release of glutamate and inhibited the expression of PKCγ in the rat spinal cord and these changes correlated with reduced postoperative pain. The treatment effect was most evident at the highest tested dose of DMED (1 µg/kg).

Effects of Shengjiangsan, white silkworm and Periostracum cicadae on cytokines in Henoch-Schönlein purpura nephritis

Henoch-Schönlein purpura (HSP, also named IgA vasculitis) is a common childhood vascular disease, which is characterized by immunoglobulin A (IgA deposition) in small blood vessels; HSP causes kidney involvement to develop Henoch-Schönlein purpura nephritis (HSPN). However, the exact pathogenesis of HSPN is not fully understood, and it is still necessary to explorer new drugs for the treatment of HSPN. In this study, bovine serum albumin (BSA), lipopolysaccharide (LPS) and carbon tetrachloride (ClC4) were used to induce IgAN in rat, and the blood stasis and heat syndrome model was established concurrently, and was combined to establish the HSPN model. The therapeutic effects of different doses of Shengjiangsan (5, 10, 20 g/kg), white silkworm (1, 2, 4 g/kg), and Periostracum cicadae (0.5, 1, 2 g/kg) on HSPN model rats were studied, then 24 h urine was collected and blood from the abdominal aorta was taken to detect the protein changes in urine and blood. Immunofluorescence staining was used assess to IgA deposition in glomeruli. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin 6 (IL-6), and immunoglobulin A (IgA) levels were measured in serum by enzyme-linked immunosorbent assay. Hematoxylin and eosin (H&E) and periodic acid Schiff (PAS), immunohistochemical staining was performed to observe the histopathological changes in kidney tissues. In addition, Western blotting was used to detect the changes in the expression levels of IgA, TNF-α, and toll-like receptor 4 (TLR4). In the results, Shengjiangsan, white silkworm, and Periostracum cicadae could significantly reduce the levels of urine protein, blood urea nitrogen (BUN) and serum creatinine (CREA) in HSPN rats. Serum levels of IgA, TNF-α, IL-1β, and IL-6 were significantly reduced in the treatment groups. The treatment group can effectively improve renal tissue inflammation and mesangial hyperplasia. The accumulation of IgA protein in renal tissue was significantly reduced in the treatment group. The expression of monocyte chemoattractant protein (MCP)-1, TLR4, and IgA were significantly reduced and responded in a dose-dependent manner. Moreover, levels of transforming growth factor beta 1 (TGF-β1) decreased in kidney tissues in the treatment groups. In conclusion, Shengjiangsan, white silkworm, and Periostracum cicadae could improve HSPN in rats by reducing renal inflammation and fibrosis, and the therapeutic effects of white silkworm and Periostracum cicadae were slightly better than Shengjiangsan.

Therapeutic effects of exercise-accompanied escitalopram on synaptic potency and long-term plasticity in the hippocampal CA1 area in rats under chronic restraint stress.

Administration of antidepressants and exercise are among the therapeutic approaches to chronic stress. Therefore, this study compared the therapeutic effects of different doses of escitalopram, exercise, and exercise-accompanied escitalopram on synaptic potency and long-term plasticity in the hippocampal CA1 area in rats under chronic restraint stress. The rats were allocated to different groups. The chronic restraint stress (6 hr/day) continued for 14 days. Injection of escitalopram (10 and 20 mg/kg) and treadmill running (1 hr/day) were performed after the stress induction. The input/output (I/O) functions and LTP induction were evaluated in the hippocampal CA1 area. The fEPSP slope and amplitude after the LTP induction significantly decreased in the chronically stressed group. However, the serum corticosterone levels had significant enhancement in this group. In addition to serum corticosterone levels, the fEPSP slope and amplitude after the LTP induction were enhanced by exercise, escitalopram 20 mg/kg alone, and exercise-accompanied escitalopram 10 and/or 20 mg/kg in chronically stressed groups. Overall, chronic stress impaired synaptic potency and long-term plasticity. These impairments were effectively reversed by exercise, escitalopram 20 mg/kg alone, and exercise-accompanied escitalopram 10 and 20 mg/kg. However, escitalopram 10 mg/kg alone could not alleviate the memory deficits in chronically stressed subjects. Therefore, exercise with both doses of escitalopram seems to have had additive effects on chronic stress conditions.

The influence of a nanoparticle gel loaded with siRNA-cyclooxygenase on flexor tendon healing: an in vivo animal study.

We investigated the influence of cyclooxygenase (COX)-1 and COX-2 siRNAs delivered through a nanoparticle-gel system on the strength of flexor tendon repairs. Sixteen flexor digitorum profundus (FDP) tendons of chicken toes were transected, repaired and wrapped with gels to evaluate gel adherence. We found that the gel adhered to the tendon surface firmly. Next, 56 tendons were used in a first set of in vivo experiments to compare the therapeutic effects of different doses of COX siRNAs. Another 15 tendons were added in a second set to further assess the effects of a dosage of 12 μg. After 4 weeks, the mean strength of the repaired tendons increased most notably in the toes treated with 12 μg COX siRNAs, and the number of samples with low strength (<35 N) was significantly smaller than in the group without molecular treatment. We conclude that COX-1 and COX-2 siRNAs delivered through a nanoparticle-gel system increased the healing strength of the repaired tendons.

Cinnamon could improve hepatic steatosis caused by a high-fat diet via enhancing hepatic beta-oxidation and inhibiting hepatic lipogenesis, oxidative damage, and inflammation in male rats.

Obesity is a health and medical problem and is known as the accumulation of fat that increases the risk of cardiovascular, type 2 diabetes mellitus, and infertility. Cinnamon is a spice that is used mainly as a flavoring additive and folk remedies to treat diabetes. Molecular mechanisms of its effects on hepatic lipogenesis and beta-oxidation, inflammation, and oxidative damage are not fully understood. Therefore, the aim of this study was to evaluate the protective and therapeutic effect of different doses of cinnamon in obese male rats. Forty-eight adult male Wister rats were randomly assigned into eight controlled and treated groups. Serum levels of lipid, glucose, and insulin profiles were measured along with liver levels of antioxidant enzymes, MDA and TNF-α. Hepatic expression of genes involved in beta-oxidation, lipogenesis, oxidative stress, and inflammation was also evaluated. Hepatic levels of oxidative and inflammatory biomarkers and serum levels of glucose, liver enzymes, insulin, and lipid profiles increased significantly in obese rats. Moreover, hepatic expression of SREBP-1c and NF-κB increased, and PPAR-alpha, CD36, FAS, CPT-1, and Nrf-2 decreased in obese rats. However, pretreatment and treatment with different doses of cinnamon in obese rats could significantly ameliorate them in obese rats. It can be concluded that cinnamon could improve hepatic steatosis caused by a high-fat diet via enhancing hepatic beta-oxidation and inhibiting hepatic lipogenesis, oxidative damage, and inflammation in male rats. PRACTICAL APPLICATIONS: Obesity as a medical and psychiatric problem is seen in more than a third of the world's population. Obesity leads to cardiovascular disease, diabetes, and in some cases even death. Cinnamon as a spice and folk remedy has long been used as a treatment for obesity and liver disease. Cinnamon has received a great of attention from the past to the present due to its pharmacological properties and in addition to its availability, cheapness and low side effects. Cinnamon can prevent dyslipidemia, hyperglycemia, oxidative damage, and inflammation by modulating multiple signaling pathways. Our results showed that cinnamon could improve hepatic steatosis caused by HFD via enhancing hepatic beta-oxidation and inhibiting hepatic lipogenesis, oxidative damage, and inflammation. Therefore, it can be recommended that cinnamon and its products can be used as a very suitable option for the production of pharmaceutical supplements for the prevention and treatment of metabolic diseases.

Dynamic Electrocardiogram under P Wave Detection Algorithm Combined with Low-Dose Betaloc in Diagnosis and Treatment of Patients with Arrhythmia after Hepatocarcinoma Resection.

This work aimed to study the diagnostic value of dynamic electrocardiogram (ECG) based on P wave detection algorithm for arrhythmia after hepatectomy in patients with primary liver cancer, and to compare the therapeutic effect of different doses of Betaloc. P wave detection algorithm was introduced for ECG automatic detection and analysis, which can be used for early diagnosis of arrhythmia. Sixty patients with arrhythmia after hepatectomy for primary liver cancer were selected as the research objects. They were randomly divided into control group, SD group, MD group, and HD group, with 15 cases in each group. No Betaloc, low-dose (≤47.5 mg), medium-dose (47.5–95 mg), and high-dose (142.5–190 mg) Betaloc were used for treatment. As a result, P wave detection algorithms can mark P waves that may be submerged in strong interference. P waves from arrhythmia database were used to verify the performance of the proposed algorithm. The prediction precision (Pp) of ventricular arrhythmia and atrial arrhythmia was 98.53% and 98.76%, respectively. Systolic blood pressure (117.35 ± 7.33, 126.44 ± 9.38, and 116.02 ± 8.2) mmHg in SD group, MD group, and HD group was significantly lower than that in control group (140.3 ± 7.21) mmHg after two weeks of treatment. Moreover, those of SD group and HD group were significantly lower than MD group (P < 0.05). The effective rate of cardiac function improvement in SD group (72.35 ± 1.21%) was significantly higher than that in control group, MD group, and HD group (38.2 ± 0.98%, 65.12 ± 1.33%, and 60.43 ± 1.25%; P < 0.05). In short, dynamic ECG based on P wave detection algorithm had high diagnostic value for arrhythmia after hepatectomy in patients with primary liver cancer. It was safe and effective for patients to choose small dose of Betaloc.

Ameliorative effects of astaxanthin on brain tissues of alzheimer's disease-like model: cross talk between neuronal-specific microRNA-124 and related pathways.

Alzheimer's disease (AD) is a chronic, progressive, multifactorial, and the most common neurodegenerative disease which causes dementia and mental deterioration in the elderly. The available treatments for AD are not disease-modifying drugs and only provide symptomatic relief. Astaxanthin (ATX), a second-generation antioxidant, is a dark red carotenoid and exhibits the highest antioxidant capacity, anti-inflammatory, neuroprotective, and antiapoptotic effects. In this study, we investigated the therapeutic effect of different doses of ATX on the cerebral cortex and hippocampus of AD-like rats. The AD-like model was induced in rats using hydrated aluminum chloride (AlCl3.6H2O) solution that was given orally at a dose of 75mg/kg daily for 6weeks. Morris water maze (MWM) behavioral test was performed to confirm the cognitive dysfunction then AD-like rats were orally treated with different doses of ATX (5, 10, and 15mg/kg) dissolved in dimethyl sulfoxide (DMSO) for six weeks. The results indicated that ATX significantly and dose-dependently improved the performance of AD-like rats treated with ATX during MWM and suppress the accumulation of amyloid β1-42 and malondialdehyde. Also, significantly inhibit acetylcholinesterase and monoamine oxidase activities and the expression of β-site amyloid precursor protein cleaving enzyme 1 (BACE 1). ATX also significantly elevated the content of acetylcholine, serotonin, and nuclear factor erythroid-2-related factor 2 (Nrf2) and miRNA-124 expression. The effect of ATX treatment was confirmed by histopathological observations using H&E stain and morphometric tissue analysis. From this study, we concluded that ATX may be a promising therapeutic agent for AD through targeting different pathogenic pathways.

Dihydroartemisinin alleviates atopic dermatitis in mice by inhibiting mast cell infiltration

To observe the therapeutic effect of different doses of dihydroartemisinin (DHA) on atopic dermatitis (AD) in mice and explore the mechanism. Forty-two C57BL/6 mice were randomly divided into 7 groups (n=6), including a blank control group, a 2, 4-dinitrochlorobenzene (DNCB)-induced AD model group, a solvent-treated group, 3 DHA treatment groups treated with 25, 75, and 125 mg/kg DHA, and a dexamethasone treatment group. The counts of skin scratches were recorded and the lesion scores were evaluated on a daily basis. After 7 consecutive days of treatment, skin tissues were sampled from the lesions on the back and ear of the mice for pathological examination with HE staining, Masson staining and toluidine blue staining. Treatment with 25, 75, and 125 mg/kg DHA and dexamethasone all alleviated AD symptoms of mice, reduced the severity scores of skin lesions, and ameliorated pathological changes of the skin tissue. DHA at 125 mg/kg produced the most obvious therapeutic effect and significantly alleviated mast cell infiltration in the lesions as compared with the other treatment groups (P < 0.05). DHA is effective for the treatment of AD in mice with an optimal dose of 125 mg/kg. The therapeutic effect of DHA is achieved probably through regulation of local immunity by inhibiting mast cell infiltration in the lesions.

Prophylactic and therapeutic effects of different doses of vitamin C on high-fat-diet-induced non-alcoholic fatty liver disease in mice

Epidemiological studies support the association between inadequate vitamin C (Vc) intake and non-alcoholic fatty liver disease (NAFLD). However, the intervention dose of Vc, and the prophylactic and therapeutic effects on NAFLD are unclear. This study aimed to investigate the prophylactic and therapeutic effects of low (LVc), medium (MVc) and high (HVc) doses of Vc on NAFLD. C57BL/6 mice were randomly assigned to prophylactic groups (mice received a high-fat diet (HFD) concomitant with different doses of Vc) and therapeutic groups (HFD-induced NAFLD mice treated with different doses of Vc). Results showed that prophylactic LVc and MVc administration reduced the risk of NAFLD development in HFD-fed mice, as evidenced by significantly lowered body weight, perirenal adipose tissue mass, and steatosis, whereas prophylactic HVc administration did not prevent HFD-induced NAFLD development. Furthermore, therapeutic MVc administration significantly ameliorated HFD-induced increase in body weight, perirenal adipose tissue mass and steatosis, whereas therapeutic LVc and HVc administration did not ameliorate NAFLD symptoms. In fact, therapeutic HVc administration significantly increased body weight, perirenal adipose tissue mass, and lobular inflammation. Moreover, prophylactic LVc administration was more effective than therapeutic LVc administration as evidenced by significantly lower body weight, perirenal adipose tissue mass, steatosis, ballooned hepatocytes, and lobular inflammation in prophylactic LVc administration. The same trends were observed between prophylactic HVc administration and therapeutic HVc administration. In addition, all Vc-administered mice exhibited low blood glucose, triglycerides and homeostasis model assessment of insulin resistance values and high adiponectin levels compared to HFD-fed mice. Our study suggested that MVc was beneficial for HFD-induced NAFLD prophylaxis and therapy. LVc prevented HFD-induced NAFLD development, while HVc for NAFLD management was risky. This study offers valuable insight into the effect of various Vc doses on NAFLD management.

Therapeutic effects of different doses of prebiotic (isolated from Saccharomyces cerevisiae) in comparison to n-3 supplement on glycemic control, lipid profiles and immunological response in diabetic rats

BackgroundThe regular intake of fiber generates numerous health benefits. However, the efficacy depends on the duration of consumption and the ingested dose. Studies investigating the optimal dose are of interest to enable the inclusion of fiber in the routine treatment of diabetic patients.ObjectiveWe aimed to evaluate the effects of different doses of β-glucan (BG—isolated from Saccharomyces cerevisiae), in comparison to n-3 supplement, on the inflammatory and metabolic parameters of Wistar rats induced to diabetes by streptozotocin.MethodsForty animals were randomly divided into six groups receiving 0 mg/kg, 10 mg/kg, 20 mg/kg, or 40 mg/kg BG daily for 4 weeks or fish oil derivative [1000 mg/kg of omega-3 fatty acids (n-3)] for the same period. One additional group was composed of healthy controls. Serum metabolic and immunological parameters were evaluated by colorimetric and ELISA assays respectively. Histopathological analysis of the liver, small intestine and pancreas were also conducted. Significant changes due to BG intake were set into regression models with second-degree fit in order to estimate the optimal BG dose to achieve health benefits.ResultsThe animals that ingested BG had lower food and water intake (p < 0.05) than the negative control group (0 mg/kg). However, consumption was still elevated in comparison to healthy controls. Blood glucose and serum levels of total cholesterol, LDL-c, and TG (p < 0.05) reduced in comparison to diabetic animals without treatment (better or similar to n-3 group depending on dose), but did not reach normal levels (in comparison to healthy controls). HDL-c was not different (p > 0.05) among all groups. These reductions were already seen with the lowest dose of 10 mg/kg. On average, the serum levels of the hepatic enzymes ALT and AST were 40% and 60% lower in the BG groups in comparison to diabetic animals without treatment (better results than n-3 group). The group receiving 40 mg/kg reached similar values of healthy controls for ALT; whereas the same result occurred from the dose of 10 mg/kg for AST. The ideal dose, estimated from the mean of all metabolic parameters was approximately 30 mg/kg/day. Regarding the immunological profile, TNF-α significantly decreased in the BG groups compared to controls (p < 0.05), reaching better values than n-3 group and similar to healthy controls. No significant differences were found between the groups in IL-1β or IL-10 (p > 0.05). No histological changes were found in the pancreas, liver, or intestine due to treatment among diabetic animals.ConclusionsBG significantly reduced blood glucose as well as serum total cholesterol, LDL-c and TG. There was a hepatoprotective effect due to the reduction in ALT and AST and a reduction in TNF-α, indicating a modulation of the immune response. In general, BG effects were better than n-3 supplement (or at least comparable) depending on the dose.

Prophylactic and Therapeutic Effect of Aqueous Stem Extract of Costus afer on Lipids and Atherogenic Profile of Albino Rats in Acetaminophen Induced Liver Toxicity

Background: Medicinal plants are widely used in Nigeria because they are believed to be effective in the treatment of various medical conditions and are also easily accessable with minimal side effect.&#x0D; Aim: This study evaluates the prophylactic and therapeutic effects of different doses (200 mg/kg, 400 mg/kg and 800 mg/kg body weight) of Costus afer on lipid profile of 50 male albino rats.&#x0D; Methodology: The research study was divided into 2 phases with 25 rats used for each phases. The 25 rats used for each phase were randomly selected into 5 groups with each group containing 5 rats. The rats used for the prophylactic phase were induced with 800 mg/kg body weight paracetamol for liver toxicity after administration of the various concentrations of aqueous stem extract of C. afer for 28 days while those used during the therapeutic phase were administered with the various concentrations of aqueous stem extract of C. afer following confirmation of liver toxicity using 800 mg/kg body weight acetaminophen. The effect of the aqueous extract was assessed by measuring the serum concentration of total cholesterol, triglycerides and high density lipoprotein using Randox reagent, while low density lipoprotein was calculated from the other parameters. Atherogenic ratios were also computed. The result obtained from the experiment was subjected to statistical analysis using Graph pad prism version 5.3 and values were considered significant at p&lt;0.05.&#x0D; Results: Total cholesterol, triglycerides and LDL levels were significantly (p&lt;0.05) reduced and HDL significantly increased in the treatment groups (prophylactic and therapeutic phases) compared to the positive control. When both phases were compared, total cholesterol and triglycerides showed significant (p&lt;0.05) difference in concentration in groups fed with 400 mg/kg, 200 mgkg while LDL-C showed significant (p&lt;0.05) variation between the two phases only at 400 mg/kg body weight. The extracts were also found to significantly (p&lt;0.05) reduce the atherogenic status of the albino rats in both phases of treatment and between each treatment phase.&#x0D; Conclusion: Findings from this study suggest that Costus afer possesses the ability to regulate paracetamol induced dyslipidaemia and improve the anti-atherogenic status of treated albino rats.

The relationships between different doses of vancomycin with blood drug trough concentration and renal dysfunction in children with severe infection in ICU

Objective To investigate the relationships between different doses of vancomycin with blood drug trough concentration and renal dysfunction in children with severe infection in intensive care unit (ICU). Methods 100 children with severe infection treated with vancomycin from January 2018 to November 2018 in the Ⅱ Department of Critical Care Medicine of Hunan Children's Hospital were studied, according to the dosage, they were divided into high-dose group [15 mg/(kg·time), 57 cases] and low-dose group [15 mg/(kg·time), 43 cases]. At the same time, according to the condition of renal dysfunction, children were divided into normal renal function group (42 cases), mild injury group (43 cases), moderate injury group (15 cases). The blood drug trough concentration was measured, and its relationship with serum creatinine (Scr), serum urea nitrogen (BUN), and renal dysfunction was analyzed. At the same time, the therapeutic effects of different doses of vancomycin were evaluated. Results The cure rate and blood drug trough concentration of children with severe infection in high-dose group were significantly higher than those in low-dose group (P<0.05), and the time to reach effective blood drug trough concentration was significantly shorter than that in low-dose group (P<0.05); the levels of serum Scr and BUN in low-dose group and high-dose group were significantly lower than those before treatment (P< 0.05); the blood drug trough concentration and the proportion of reaching the target trough concentration in mild injury group were significantly higher than those in normal group and moderate injury group (P<0.05); the dose of vancomycin in mild injury group and moderate injury group was significantly higher than that in normal group (P<0.05), and the course of treatment in mild injury group and moderate injury group was lower than that in normal group (P<0.05). Conclusions The high dose of vancomycin 15 mg/(kg/time) is effective in the treatment of ICU children with severe infection. the blood drug trough concentration and renal dysfunction should be monitored and individualized treatment plan should be formulated. Key words: Vancomycin; Drug dosage; Plasma concentration; Renal dysfunction; Infection; Child

The effects of different doses of teriparatide on bisphosphonate‐related osteonecrosis of the jaw in mice

This study aimed to investigate the therapeutic effect of different doses of teriparatide (TPTD) on bisphosphonate-related osteonecrosis of the jaw (BRONJ). To establish the BRONJ model, 20 mice were randomly divided into two groups: a group that received tail vein administration of zoledronic acid with dexamethasone (ZA-125 µg/kg, DEX 5 mg/kg) and a group that received saline weekly. The mice subsequently underwent bilateral maxillary first molar extraction. After 8 weeks of modeling administration, the maxilla samples were examined by micro-computed tomography and histological staining (haematoxylin-eosin, Masson's trichrome, and tartrate-resistant acid phosphatase) and the cytokine level was measured (enzyme-linked immunosorbent assay and western blot). To determine the role of TPTD in BRONJ, the same protocol as previously described was applied in 100 mice (80 received ZA+DEX and 20 received saline). After 8 weeks of modeling administration, 80 ZA+DEX mice were randomly divided into four groups: three groups with subcutaneous administration of TPTD (i.e. T1-3, T2-10, and T3-30 µg/kg/d) and one group with saline daily for the next 8 weeks. The other 20 saline mice continued to receive saline daily. In PART ONE, the level of receptor activator of nuclear factor kappa-Β ligand and the numbers of osteoclasts differed between the model and control groups. In PART TWO, we found that TPTD had a positive effect on BRONJ in a mouse model based on clinical and histomorphological observations. Among the three treatment groups, the T1 and T2 groups significantly differed from the model group, whereas the T3 group showed no statistical differences. Subcutaneous administration of TPTD has a beneficial effect on BRONJ in mice. Nevertheless, further studies are needed to determine whether the therapeutic effect on BRONJ is dose-dependent.

Efficacy of intermittent epidural dexamethasone bolus for zoster-associated pain beyond the acute phase.

Herpes zoster develops when latent varicella zoster virus is reactivated in the trigeminal or dorsal root ganglions. Zoster-associated pain (ZAP) is neuropathic pain caused by the herpes zoster virus. Histological studies of postherpetic neuralgia patients suggest that inflammation is involved in ZAP. The effectiveness of local anesthetic and steroid epidural injections in ZAP patients has been reported. However, most studies included patients with acute herpes zoster, and the safety and therapeutic effects of different doses of epidural steroids in ZAP patients remain elusive. In this study, we randomly assigned 42 patients with severe ZAP beyond the acute phase, as determined by a numeric rating scale (NRS) score ≥7, to receive continuous epidural infusion of local anesthetics with either a one-time 5-mg dose or intermittent repeated doses (15 mg total) of dexamethasone. We found that intermittent repeated epidural dexamethasone bolus resulted in reduced NRS scores and an increased likelihood of complete remission in ZAP patients without any adverse effects. Thus, our results suggest that intermittent repeated epidural dexamethasone administration is safe and effective for treatment of ZAP beyond the acute phase.

Mid-dose losartan mitigates diabetes-induced hepatic damage by regulating iNOS, eNOS, VEGF, and NF-κB expressions

Background/aimLosartan, an antihypertensive drug, is highly preferred in patients with diabetes mellitus (DM) and hypertension because of its retarding effect on diabetic nephropathy. In this study, we investigated the potential therapeutic effect of different doses of losartan on hepatic damage in a streptozotocin (STZ, 50 mg/kg)-induced DM model in rats.Materials and methodsIn this study, five different groups were formed: control, DM, low-dose losartan (5 mg/kg), mid-dose losartan (20 mg/kg), and high-dose losartan (80 mg/kg). Liver tissues of experimental groups were evaluated immunohistochemically for TUNEL, iNOS, eNOS, VEGF, and NF-κB pathways. In addition to immunohistochemical analysis, analyses of SOD and MDA, which are oxidative stress markers, were also performed and the results were evaluated together.ResultsWhen biochemical and immunohistochemical findings were evaluated together, it was found that the results obtained from the mid-dose losartan group were closer to those of the control than the other groups.ConclusionThis study indicated that mid-dose losartan administration may have a therapeutic effect by inhibiting apoptosis and regulating iNOS, eNOS, VEGF, and NF-κB protein expressions in DM-induced hepatic damage.

Efficacy of different doses of botulinum toxin A injections on bromhidrosis in adolescents

Objective To explore the therapeutic effect of different doses of botulinum toxin A injections on bromhidrosis. Methods A total of 200 cases were divided into mild-to-moderate group (N=100) and severe group (N=100) based on the grade of bromhidrosis, and each group was further divided into two groups: low dose group (50 cases) were treated by botulinum toxin A injections (100 U) and high dose group (50 cases) were treated with 200 U for bilateral axillary. The total effective rate and recurrence rate in both groups were compared. Results In the mild to moderate group, after treatment for 3 months, the total effective rate of both groups had no statistical difference (P>0.05), and the same with recurrence rate in 6 months follow-up (P>0.05). In the severe group, after treatment for 3 months, the total effective rate of the high dose group (82%) was significantly higher than that of the low dose group (64%), with statistical significance (χ2=4.110, P<0.05). After 6 months follow-up, recurrence rate in the high dose group (22%) was significantly lower than that of the low dose group(46%), with statistical significance (χ2=6.417, P<0.05). Conclusions A suitable dose of botulinum toxin A can be selected based on the severity of bromhidrosis, which is a individualized therapy for cost savings and might have potential benefits for patients with osmidrosis. Key words: Bromidrosis; Botulinum toxins, type A; Dose-response relationship, drug; Treatment outcome; Disease classification

Therapeutic effect of different doses of Ligustrazine on non-proliferative diabetic retinopathy

Therapeutic effect of different doses of Ligustrazine on non-proliferative diabetic retinopathy