Body Weight Dose Research Articles

Anti-inflammatory effect of caffeic acid phenethyl ester supplementation on TNF-α and NF-κB expressions throughout experimental tooth movement in vivo

Context: Orthodontic tooth movement (OTM) changes the periodontal tissue and increases the incidence of root resorption (OIRR). Caffeic acid phenethyl ester (CAPE), an antioxidant and anti-inflammatory chemical generated from honey propolis, might be useful in controlling inflammation during OTM and so reducing the risk of OIRR. Aims: To evaluate if CAPE supplementation has an anti-inflammatory impact on tumor necrosis factor-α (TNF-α) and nuclear transcription factor κB (NF-κB) during experimental OTM in male Wistar rats (Rattus novergicus). Methods: Forty-eight healthy male Wistar rats were divided into positive control group (OTM 10 g/mm2 force application) and experimental group (OTM application and CAPE administration). Each groups were observed for 3, 7, 14 days. A nickel-titanium closed coil spring that was 8.0 mm long, thick was inserted between the upper left first molar and upper central incisor in order to move the molar mesially. A 20 mg/kg body weight dose of CAPE was taken orally. Using immunohistochemistry, the expression of TNF-α and NF-κB was examined on the compression side of the OTM. Both the Tukey's honest significant difference test and the one-way analysis of variance test were applied (p<0.05). Results: TNF-α and NF-κB expression in the compression side differed considerably across groups (p<0.05). Daily administration of CAPE significantly downregulates TNF-α and NF-κB expression on the compression side. Conclusions: Administration of CAPE throughout OTM can successfully reduce the number of TNF-α and NF-κB expressions in the compression side in vivo.

Are there effects of Extract Coffee Robust Lampung as Immunonutrition in Chicken against Salmonellosis?

The poultry industry was an industry that supported the nutritional needs of all individuals and the world's food needs. Coffee was a natural ingredient consisting of antioxidant molecules such as Chlorogenic Acid (CGA). This research using ISA brown chicken layer, which divided into five groups such as healthy chicken (control group (C-)), chicken infected with Salmonella enteritidis 108 CFU/ml (control group (C+)), chicken infected with S. enteritidis 108CFU/ml and extract Coffee consecutive 500, 1000 and 1500 mg/kg body weight (BW) group (T1, T2, and T3). The relative level of TCD4, CD8, and CD45 cells was performed with One way ANOVA test. The research results showed that the relative level of TCD4+, TCD8+ and TCD45+ cells in T1 and T2 groups was not significant with the negative control group. The conclusion is that extracting Coffee in the T1 and T2 groups with a 500-1000mg/kg BW dose could regulate immune cell activation in chicken infected by S. enteritidis bacteria.

Comparative clinical outcome following individualized follitropin delta dosing in Chinese women undergoing ovarian stimulation for in vitro fertilization /intracytoplasmic sperm injection

BackgroundTo compare the efficacy and safety of follitropin delta in its individualized fixed-dose regimen with follitropin alfa in a conventional adjustable dosing regimen in Chinese women. MethodsThis was a subgroup analysis of the randomized, multi-center, assessor-blind, non-inferiority trial (GRAPE) including 759 Chinese women (aged 20–40 years) recruited in 16 reproductive medicine clinics in China. Women were randomized in a 1:1 ratio to be treated with either follitropin delta dose based on anti-Müllerian hormone (AMH) and body weight or conventional dosing with follitropin alfa following a gonadotropin-releasing hormone (GnRH) antagonist protocol. The primary outcome was ongoing pregnancy rate assessed 10–11 weeks after embryo transfer in the fresh cycle (non-inferiority margin -10.0%).Results378 in the follitropin delta group and 381 in the follitropin alfa group were randomized and exposed. Non-inferiority was confirmed with respect to ongoing pregnancy with rates of 31.0% vs. 25.7% for follitropin delta compared to follitropin alfa, estimated mean difference of 5.1% (95% confidence interval (CI) -1.3% to 11.5%). The clinical pregnancy rate (35.4% vs. 31.5%, P = 0.239) and live birth rate (31.0% vs. 25.5%, P = 0.101) were comparable between the follitropin delta group and the follitropin alfa group. Overall, the individualized follitropin delta treatment resulted in fewer oocytes retrieved compared to follitropin alfa treatment (10.3 ± 6.2 vs. 12.5 ± 7.5, P < 0.001), which was mainly due to fewer oocytes (10.5 ± 6.4 vs. 13.9 ± 7.8) in women with AMH ≥ 15 pmol/L. Accordingly there was a lower incidence of early ovarian hyper-stimulation syndrome (OHSS) and/or preventive interventions (6.1% vs. 11.0%, P = 0.013). A daily follitropin delta dose of 10.2 µg (95% CI: 9.3—11.2 µg) was estimated to provide the same number of oocytes retrieved as a starting dose of 150 IU/d of follitropin alfa.ConclusionFollitropin delta in its individualized fixed-dose regimen showed similar efficacy and improved safety compared with follitropin alfa in a conventional adjustable dosing regimen in Chinese women.Clinical trial registration numberNCT03296527.

PHYTOCHEMICAL AND PHARMACOLOGICAL EVALUATION OF Cucurbita maxima Duchesne AND Euphorbia royleana Boiss

Phytochemical analysis of the ethanolic extract of the leaves of Cucurbita maxima indicated the presence of reducing sugars, alkaloids, saponins, tannin, steroid and glycosides whereas Euphorbia royleana indicated the presence of glycosides, alkaloids, steroids and tannin. The possible analgesic and anti-oxidant activities of Cucurbita maxima and Euphorbia royleana were investigated. Cucurbita maxima exhibited inhibition of writhing reflex 16.13% and 41.94% respectively (P&lt;0.001 and P&lt;0.001) and Euphorbia royleana exhibited inhibition of writhing reflex 19.35% and 45.16% respectively (P&lt;0.02 and P&lt;0.001) on animal model (Swiss Albino mice) at 250 and 500mg/kg body weight dose level. Diclofenac sodium was used as standard drug. Both plants showed little antioxidant activity, both qualitatively and quantitatively. In the quantitative assay, Cucurbita maxima and Euphorbia royleana displayed free radical scavenging activity in the DPPH assay IC50 = 218 µg/ml. and IC50 = 237 µg/ml respectively whereas that for ascorbic acid was IC50 = 17 µg/ml. The results provide a support for the use of this plant as analgesic and antioxidant.

De-intensification of basal-bolus insulin regimen after initiation of a GLP-1 RA improves glycaemic control and promotes weight loss in subjects with type 2 diabetes.

To evaluate the impact of adding a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in people with type 2 diabetes (T2D) in basal-bolus (BB) insulin regimen, on insulin requirement, HbA1c, weight loss up to 24months. Data on subjects with T2D on BB who initiated a GLP-1 RA have been retrospectively collected. HbA1c, body weight, and insulin dose were recorded at baseline, 6, 12, and 24months after initiation of GLP-1 RA therapy. A linear mixed model for repeated measures was used to evaluate the changes in HbA1c, body weight, and insulin requirement over time. We included 156 subjects (63.5% males; age 62 ± 11years, HbA1c 70 ± 22.0mmol/mol; 8.6 ± 4.2%). Compared to baseline, HbA1c and body weight were significantly lower at 6months after introducing a GLP-1RA and remained stable up to 24months (all p < 0.0001 vs. baseline). At 24months, 81% of subjects discontinued prandial insulin, while 38.6% discontinued basal insulin as well. Insulin requirement at baseline (aOR 0.144; 95% CI, 0.046-0.456; P = 0.001) was the only significant predictor of prandial insulin discontinuation. Replacing prandial insulin with GLP-1 RA is a valuable strategy to simplify the BB insulin regimen while improving glycaemic control and promoting weight loss in subjects with T2D.

Pharmacokinetics of hydroxychloroquine in Japanese systemic lupus erythematosus patients with renal impairment.

Reduction of the hydroxychloroquine (HCQ) dosage is recommended in systemic lupus erythematosus (SLE) patients with renal impairment, but a pharmacokinetics (PK) study of patients with renal impairment has not yet been performed. We investigated the PK of both single and multiple doses of HCQ and its metabolites in SLE patients with renal impairment who newly started HCQ at a daily dose of 300 mg based on an ideal body weight dosage of 6.5 mg/kg. Population PK analysis was performed using a non-linear mixed-effects model. In total, 219 samples from 21 patients were analysed. The PK of HCQ in blood after single and multiple oral administrations followed the two-compartment model. At steady state, the concentration ratio of HCQ to each metabolite was HCQ:desethylhydroxychloroquine:desethylchloroquine:bisdesethylchloroquine = 1:0.28:0.1:0.06. The HCQ concentration correlated positively with that of each metabolite. The estimated values (relative standard error) of the population PK parameters were the total clearance at 110 l/h (31%) and a central volume of distribution of 398 l (19%). Co-administration of prednisolone and age, but not renal impairment, were factors affecting the total clearance of HCQ. From the PK perspective, a dosage reduction is unnecessary in SLE patients with impaired renal function.

Preliminary Investigative Study on the Blood Pressure-Lowering Potential of Aqueous Leaf Extract of Simarouba glauca (AESG) on Normotensive Adult Wistar Rats

Studies have shown that plants possess medicinal properties and compounds are beneficial in managing and treating diseases, including high blood pressure and related cardiovascular conditions. Simarouba glauca (SG) has been widely reported to possess antibacterial activity, anti-oxidant, anti-proliferative and hemolytic activity; amongst others. However, there is paucity of data on its effect on blood pressure. Hence, the study research aimed at assessing the hypotensive prospect inherent in the aqueous leaf extract of Simarouba glauca (AESG) on normotensive male Wistar rats. The study was conducted using adult male Wistar rats (n = 3), a urethane/thiopental (1205/20 mg/kg) anesthesia and a chart paper attached to Ugo Basile Uni-recorder Model 400700 data capsule. Under full anesthesia, the rat’s trachea and the carotid artery were cannulated for assisted respiration and blood pressure measurement. At stable variables; following the administration of 0.2 mL normal saline, the AESG was administered intravenously via the caudal vein at 2.5 and 5.0 mg/kg body weight dose respectively. The data was recorded on a chart; indicated the characteristic dose-dependent hypotensive effect of AESG on normotensive rats; at doses of 2.5 mg/kg and 5.0 mg/kg, with marked decreases in the systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) from basal levels of 127.83 ± 1.01 mmHg, 91.00 ± 1.00 mm Hg and 103.27 ± 0.99 mm Hg respectively. The outcome of the preliminary investigation indicates that the AESG demonstrated a hypotensive effect on the BP of normotensive male Wistar rats dependent on varying doses administered; indicative of further evaluation.

Biochemical and Ultrastructural Studies for Toxicity of Kaempferol Derivative Recovered from the Plant Lysimachia Ramosa

Leaves of Lysimachia ramosa are used by various tribes of Meghalaya to cure intestinal helminth infections. Preliminary investigations disclosed impressive anthelmintic effects of the kaempferol derivative, an active component of the plant, however, toxic effects on its consumers, if any, are not known. Therefore, the present study has been undertaken to investigate the acute and sub-acute toxic effects of kaempferol derivative, of the plant, taking Wistar rats as a model. Following OECD 407, 250 mg, 500 mg, and 1000 mg/kg body weight doses of the active component have been selected to treat the animals for 28 days. On the 29th day, the animals have been sacrificed to assess different toxicological effects on animals. The LD50 value of the anthelmintic component was found to be more than 5000 mg/kg body weight of rats. Histological, ultrastructural, haematological, biochemical, andorgano-somatic (HSI and RSI) studies demonstrate changes in surface characteristics of various cellular organelles of different vital organs such as the liver, kidney, and intestine. Alterations were also recorded in different vital enzymes such as AST, ALT, and ALP in the phytochemical exposed rats at higher doses. The results revealed that treatment with the active component at a higher concentration may lead to toxicological effects if treatment persists for a longer period.

Biological and phytochemical characterization of Phragmanthera regularis (Loranthaceae) from Ethiopia

Phragmanthera regularis is a hemi-parasitic shrub. It is known for treating various health ailments. The aim of this study was to evaluate the antimicrobial activity, toxicity, and chemical characterization of the leaf extracts of P regularis collected from the Schinus molle host plant in Ethiopia. The antimicrobial properties of crude extracts obtained with chloroform, ethyl acetate, methanol, and water solvents were assayed against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The methanol extract significantly inhibited the growth of S. aureus, E. coli and P. aeruginosa were resistant to any of these solvent extracts. The methanol extract was tested at 175, 550, and 2000 mg/kg body weight doses in white mice and did not reveal any toxicity. The LC-MS qTOF analysis detected flavonoids, phenolic acids, and alkaloids in the crude methanol extract. Further study is needed to investigate the effectiveness of these compounds against S. aureus.

Fertility regulatory potential of Persicaria hydropiper (L.) Delarbre methanolic root extract in female albino mice: An insight into the phytochemicals present and role of the extract in contraception

People from some parts of the world traditionally depend on different herbal medicines for fertility regulation. The Mishing women of Assam, India have been using the dry root powder of Persicaria hydropiper for years as a birth control medicine. The present study was designed to investigate the chemical composition of methanolic extract from the dry roots of P. hydropiper as well as to study its anti-implantation effect. P. hydropiper roots were collected from paddy fields and the methanolic extract was prepared using dry powdered roots. Gas chromatography-mass spectrometry (GCMS) analysis of the methanolic root extract was performed for phytochemical analysis. The estrous cycle of the female mice was monitored by observation of the cells in the vaginal smear. The estrogenic and anti-implantation effect was observed using routine histological procedures with Haematoxylin & Eosin staining performed in mice. Total serum cholesterol level was also measured. The GCMS analysis revealed the presence of stigmasterol and 3-deoxyestradiol, which are known to possess antifertility properties. The extract (1000 mg/kg bodyweight dose) altered the duration and sequence of the estrous cycle of cyclic females with a prolonged metestrous of 2 days, followed by an early estrous. There was hyperplasia in the endometrial epithelium and even shedding of the same on high duration treatment on day 6. There was a significant (p < 0.05) rise in total cholesterol levels in the treated groups. The highest rise was observed in the day 1 group (from 67.91 ± 1.98 to 147.53 ± 3.20 mg/dl) while the lowest change was there in the day 2 group (from 78.76 ± 2.04 to 103.26 ± 2.34 mg/dl). The presence of compounds like stigmasterol and 3-deoxyestradiol with profound antifertility properties possibly has an influence on the molecular pathway for embryo implantation. The changes in uterine histoarchitecture in the form of uterine hyperplasia on treatment with the extract point out towards the effect of the estrogenic compounds. Such implantation preventing results provides support to the traditional belief and opens the door for new drug discovery for reproduction regulation. A detailed molecular study is necessary in this regard.

Histopathological Evaluation of Ethanolic Leaf Extract of Lippia adoensis on Liver, Kidney, and Biochemical Parameters in Swiss Albino Mice.

BackgroundEighty percent of Ethiopians use traditional medicine, one of which is the leaf of Lippea adoensis.ObjectiveTo investigate subacute toxicity of aqueous extracts of L. adoensis leaves on the liver and kidney and biochemical parameters in Swiss albino mice.MethodsLD50 was assessed with nine experimental groups and one control group of adult female Swiss albino mice (five in each group). In the subacute study, 40 mice of both sexes were randomly divided into four groups of ten mice (both sexes) per group. Group I served as controls and received distilled water and feed only. Groups II–IV were used as treatment groups. They received calculated doses of aqueous leaf extracts orally at doses of 500 mg/kg, 1000 mg/kg, and 2000 mg/kg body weight, respectively.ResultsSince 80% of deaths occurred at the 10,000 mg/kg body-weight dose in this experiment, LD50 was considered to be <10,000 mg/kg. In the subacute test, general signs of toxicity like hypoactivity, piloerection, lethargy, and a single episode of convulsion were observed at the 2000 mg/kg dose. Beginning from the third week of administration, both male and female mice receiving 500 mg/kg and 2000 mg/kg and all treatment groups in the fourth week showed significant (P<0.05) weight loss compared to controls. Biochemical parameters were found to increase in all groups treated with ethanolic leaf extracts. Several histopathological changes like congestion, hemorrhage, severe necrosis, and infiltration of inflammatory cells in both liver and kidney in the L. adoensis–treated rats were observed at all doses.ConclusionIn the present study, the ethanolic leaf extracts of L. adoensis produced dose-dependent weight loss and histopathological and biochemical changes in Swiss albino mice.

Hypolipidemic Potential of Ethyl acetate Extract of Hyphaene thebaica Fruit in Streptozotocin-induced Diabetic Rats

Hyperlipidemia is characterized by elevated levels of Triglycerides, Cholesterol, LDL, and decreased levels of HDL are challenges in the management of Diabetes mellitus which might lead to death. This study aimed to determine the hypolipidemic potential of ethyl acetate extract of Hyphaene thebaica fruit in streptozotocin-induced diabetic rats. The hypolipidemic potential of H. thebaica fruit in streptozotocin-induced diabetic rats was determined. Rats were divided into six groups. Treatment groups were administered the extract at doses of 400 and 200 mg/kg body weight. Oral administration of the extract at 400 mg/kg body weight for four weeks significantly (p &lt; 0.05) decreased the levels of total cholesterol (151.7 mg/dl ±2.40), Triglyceride (84.0 mg/dl ±1.15), LDL (75.2 mg/dl ±1.20) and increased HDL (39.3 mg/dl ±1.88) level. However no significant (p &lt; 0.05) difference was observed between the 400 and 200 mg/kg body weight dose. Conclusively, H. thebaica can be used as a medicinal plant due to its protective action against dyslipidemic complications of diabetes mellitus.

The role of autophagy in high-fat diet-induced insulin resistance of adipose tissues in mice.

AimsStudies have observed changes in autophagic flux in the adipose tissue of type 2 diabetes patients with obesity. However, the role of autophagy in obesity-induced insulin resistance is unclear. We propose to confirm the effect of a high-fat diet (HFD) on autophagy and insulin signaling transduction from adipose tissue to clarify whether altered autophagy-mediated HFD induces insulin resistance, and to elucidate the possible mechanisms in autophagy-regulated adipose insulin sensitivity.MethodsEight-week-old male C57BL/6 mice were fed with HFD to confirm the effect of HFD on autophagy and insulin signaling transduction from adipose tissue. Differentiated 3T3-L1 adipocytes were treated with 1.2 mM fatty acids (FAs) and 50 nM Bafilomycin A1 to determine the autophagic flux. 2.5 mg/kg body weight dose of Chloroquine (CQ) in PBS was locally injected into mouse epididymal adipose (10 and 24 h) and 40 µM of CQ to 3T3-L1 adipocytes for 24 h to evaluate the role of autophagy in insulin signaling transduction.ResultsThe HFD treatment resulted in a significant increase in SQSTM1/p62, Rubicon expression, and C/EBP homologous protein (CHOP) expression, yet the insulin capability to induce Akt (Ser473) and GSK3β (Ser9) phosphorylation were reduced. PHLPP1 and PTEN remain unchanged after CQ injection. In differentiated 3T3-L1 adipocytes treated with CQ, although the amount of phospho-Akt stimulated by insulin in the CQ-treated group was significantly lower, CHOP expressions and cleaved caspase-3 were increased and bafilomycin A1 induced less accumulation of LC3-II protein.ConclusionLong-term high-fat diet promotes insulin resistance, late-stage autophagy inhibition, ER stress, and apoptosis in adipose tissue. Autophagy suppression may not affect insulin signaling transduction via phosphatase expression but indirectly causes insulin resistance through ER stress or apoptosis.

Effect of Mentone® on depression- and anxiety-like profiles and regional brain neurochemistry in the adolescent Wistar Kyoto rat, a putative model of endogenous depression

Objectives: Antidepressants, when prescribed to treat adolescent depression tend to induce adverse effects, including suicidal tendencies. This is because the adolescent brain circuitry is still maturing and is therefore extremely vulnerable. As such, the search is on for compounds for use in complementary/alternative medicine. Polyherbal formulations are widely used as therapeutic alternatives for the treatment of depression. Such formulations and plant extracts are being studied in adult rodent models using standard pharmacological parameters, but not much emphasis has been given to testing the same in adolescents and endogenous animal models of depression. Therefore, the present study was focused on testing out the effect of the polyherbal formulation Mentone® on depression- and anxiety-like profiles and brain neurochemistry in the adolescent Wistar Kyoto rat (WKY), a putative model of endogenous and treatment-resistant depression (TRD). Materials and Methods: Mentone®, a polyherbal formulation comprising of four different plant species: Centella asiatica (Brahmi), Evolvulus alsinoides (Shankapushpi), Tinospora cordifolia (Guduchi), and Glycyrrhiza glabra (Yashtimadhu) was tested at two (18 and 36 mg/kg body weight) doses from the post-natal day (pnd) 25 to pnd 42 using standard neurobehavioral paradigms. Vehicular controls were intubated with saline and positive controls with 10 mg/kg body weight of conventional antidepressant, Fluoxetine. From pnd 35 onwards, animals were tested on a battery of tests, including sucrose preference, novel open field, elevated plus maze, and forced swim or Porsolt’s learned helplessness test. On pnd 42, animals were sacrificed and brain regional tissues such as the Prefrontal cortex (PFC), Striatum (Str), Nucleus Accumbens (NAc), and Hippocampus were microdissected out and subjected to reverse phase HPLC for the separation and quantification of monoamines: Norepinephrine (NE), dopamine (DA), serotonin (5-HT) and their metabolites, 3,4-Dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) in reference to external standards. Results: Mentone® reversed anhedonia by increasing sucrose consumption in Mentone®-treated as compared to Fluoxetine-treated groups. However, there was no effect on anxiety-related parameters in the novel open field or elevated plus-maze. Mentone® exhibited significant anti-depressant-like effects as indicated by its ability to reduce swim stress-induced immobility in Porsolt’s behavioural despair test with a concomitant increase in climbing or struggling behaviour, signifying reversal of depressive-like symptomatology. HPLC-based separation and quantification of brain regional levels of monoamines and their metabolites revealed increased DA levels in NAc and Str in treated groups with decreased levels of metabolite DOPAC in Mentone®-treated groups indicating increased DA tone. Significantly reduced 5-HT metabolite 5-HIAA levels in both PFC and Str is indicative of increased 5-HT tone in both Mentone®- and Fluoxetine-treated groups. NE was variably affected. Conclusion: While no anxiolytic effects and differential neurochemical effects were observed in brain regional areas in relation to Mentone® and Fluoxetine treatment, anhedonia and forced swim test, which are gold-standard tests for assessing depressive-like profiles indicated an effect of Mentone® that was on par with Fluoxetine. Thus, studies on such Ayurvedic formulations would enable a teasing out or differentiation between anxiolytic-like and depressive-like symptomatology and could constitute a source that holds promise in the development of complementary/alternative therapies for the treatment of depression in general and TRD in particular.

Human Neutrophil Defensins Disrupt Liver Interendothelial Junctions and Aggravate Sepsis

Human neutrophil peptides 1-3 (HNP1-3), also known as human α-defensins, are the most abundant neutrophil granule proteins. The genes that encode HNP1-3, DEFA1/DEFA3, exhibit extensive copy number variations, which correlate well with their protein levels. Human and mouse studies have shown that increased copy numbers of DEFA1/DEFA3 worsen sepsis outcomes. Additionally, high concentrations of HNP1-3 in body fluids have been reported in patients with sepsis. However, direct evidence for the pathogenic role of HNP1-3 proteins during sepsis progression is lacking. In current study, sepsis was induced by means of cecal puncture and ligation. Various doses of HNP-1 (low dose with 0.5 mg/kg body weight and high dose with 10 mg/kg body weight) or phosphate buffer saline were intraperitoneally administered to mice at six hours after sepsis onset. Survival rate was monitored, and vascular permeability, endothelial cell pyroptosis, and immunofluorescence of endothelial adherens junction protein vascular endothelial-cadherin were evaluated. The administration of a high dose of HNP-1 after sepsis onset led to increased mortality, more severe liver injury, and increased vascular permeability in the liver and mesentery. The injection of high dose of HNP-1 did not directly induce liver endothelial cell death but destroyed interendothelial junctions in the liver. Moreover, genetic deficiency of nucleotide-binding oligomerization domain-like receptor protein-3 or caspase-1 abrogated the high mortality and disrupted liver interendothelial junctions caused by high dose of HNP-1 during sepsis. This study directly demonstrates that neutrophil defensins play a key role in regulating endothelial stability during sepsis development.

Antidiabetic effects of Psidium x durbanensis Baijnath & Ramcharun ined. (Myrtaceae) leaf extract on streptozotocin-induced diabetes in rats

Ethnopharmacological relevancePsidium guajava L. leaves are used to treat diabetes in South African folkloric medicine and in other parts of the world. Psidium x durbanensis Baijnath & Ramcharun ined. (PD) is a natural sterile hybrid and congener of Psidium guajava that is expected to share the medicinal properties of the genus Psidium and is widely distributed in South Africa.Aim of the study: This study investigates the antioxidant, antidiabetic effects, and mechanisms of action of hydro-methanolic leaf extracts of PD on streptozotocin-induced diabetes in rats. Material and methodsPhytochemical constituents of hydro-methanolic extract of PD were analyzed by gas chromatography-mass spectrometry (GC-MS). Male Wistar rats 250–300 g body weight (BW) were rendered diabetic after a single intraperitoneal injection with streptozotocin, 45 mg/kg BW. The diabetic rats were treated with hydro-methanolic (20:80 v/v) leaf extracts of PD (400 mg/kg/BW) or subcutaneous injections of regular insulin (2.0U/kg/BW, bid) for 56 days. The body weights of the animals were recorded daily. Fasting blood glucose, glucose tolerance tests, and insulin resistance index were measured. The effects of the extracts on total superoxide dismutase, catalase, and reduced glutathione activities, histopathology, and gene expression of insulin receptor substrate 1 and glucose transporter 4 were determined in the liver, pancreas, and gastrocnemius muscles of the rats. ResultsIn the acute toxicity studies, there were no signs of toxicity observed for PD up to 2000 mg/kg BW doses. Diabetic animals showed significant weight loss, elevated and reduced fasting blood glucose and insulin, respectively, impaired glucose tolerance and diminished antioxidant enzymes’ activities compared to controls. Treatment with PD hydro-methanolic leaf extracts improved body weight, glucose tolerance, insulin resistance, and antioxidant enzymes but not plasma insulin in diabetic animals compared to controls, respectively. GC-MS analysis identified organic acids, alcohols, vitamins, terpenoids, and esters in the extracts. Treatment with PD improved glucose uptake by stimulating mRNA expression of GLUT 4 in gastrocnemius muscles of diabetic animals compared to the untreated control and also restored histological aberrations in the pancreas and liver of diabetic rats compared with the untreated control rats. ConclusionCollectively, the present study suggests that treatment with PD leaf extracts significantly ameliorated diabetes symptoms and oxidative stress in rats, and these effects may be linked to the bioactive phytoconstituents present in the plant. This study further suggests that PD improves insulin resistance by increasing glucose uptake in gastrocnemius muscles in an insulin-independent manner.

​Surgical Management of Mechanical Intestinal Ileus under Right Paravertebral Nerve Block and Lignocaine Continuous Rate of Infusion in Cattle

Background: Mechanical intestinal ileus is an abdominal emergency that is potentially life threatening in cattle. Early diagnosis and surgical correction is challenging for clinician under field conditions. Successful outcome depends upon effective management of visceral pain during surgical procedure and restoration of early intestinal motility. The present study is aimed to study the quality of visceral analgesia using right paravertebral nerve block and lignocaine continuous rate of infusion in standing surgery and prokinetic effect of azithromycin. Methods: The present work was carried out from April 2019 to September 2021, in 6 cattle presented to the veterinary clinical complex, veterinary college and research institute, Namakkal with a history of not voiding the dung. In all the cases, clinical, haematological, biochemical, ultrasonographic, anaesthetic, prokinetic evaluation and surgical management was performed. Result: In the present study, inclusion of lignocaine as intravenous bolus @ 2mg/kg body weight and continuous rate infusion (CRI) dose of 50 µg/kg/min produced good quality of visceral analgesia and no animal was recumbent intraoperatively. Prokinetic action of azithromycin was found effective to control the post-operative ileus in intestinal surgical procedures.

Prophylactic Anti-Osteoporotic Effect of Matricaria chamomilla L. Flower Using Steroid-Induced Osteoporosis in Rat Model and Molecular Modelling Approaches.

The anti-osteoporotic activity of ethanol extract from the Matricaria chamomilla L. flower was evaluated using steroid-induced osteoporosis in a rat model for the first time. Biochemical parameters such as serum calcium, phosphate, magnesium, creatinine, and alkaline phosphatase were assessed. At a 400 mg/kg body weight dose, the extract showed 54.01% and 27.73% reduction in serum calcium and phosphate ions serum levels, respectively. Meanwhile, it showed a 20% elevation in serum magnesium level, compared to the steroid-treated group. It also showed a significant decrease in creatinine and alkaline phosphatase levels, by 29.41% and 27.83%, respectively. The obtained results were further supported by biomechanical analyses, which revealed that a 400 mg/kg body weight dose of the flower extract increased bone strength and thickness. At the same time, it does not affect the bone length, compared to the diseased group. Histopathological examination revealed that the extract showed a significant increase in trabecular thickness, and it had restored the architecture of the cortical and trabecular structure with well-organized bone matrix. The possible inhibitory effect of the major phenolic compounds identified from the plant extract on cathepsin K was investigated using molecular docking. Rutin (4) had the best-fitting score within the active site, as evidenced by the free binding energy, (∆G = −54.19 Kcal/mol). ADMET/TOPKAT revealed that the examined compounds had variable pharmacodynamics and pharmacokinetic properties that could be improved to enhance the bioavailability during incorporation in various dosage forms. Thus, it can be concluded that this plant extract showed potential therapeutic benefits for osteoporosis.

Platelet inhibition by low-dose aspirin is not influenced by body mass or weight

Aspirin’s clinical efficacy may be influenced by body weight and mass. Although inadequate platelet inhibition by aspirin is suggested as responsible, evidence for this in non-diabetic patients is sparse. We investigated the influence of body weight and mass on aspirin’s inhibition of platelet aggregation in healthy adults without diabetes. Cohort one (NYU, n = 84) had light transmission aggregometry (LTA) of platelet-rich plasma to submaximal adenosine diphosphate (ADP) and arachidonic acid (AA) before and following 1 week of daily 81 mg non-enteric coated aspirin. Subjects in the validation cohort (Duke, n = 66) were randomized to 81 mg or 325 mg non-enteric coated aspirin for 4 weeks, immediately followed by 4 weeks of the other dose, with LTA to submaximal collagen, ADP, and AA before and after each dosage period. Body mass index (BMI) range was 18.0–57.5 kg/m2 and 25% were obese. Inhibition of platelet aggregation was similar irrespective of BMI, body weight and aspirin dose. There was no correlation between platelet aggregation before or after aspirin with BMI or body weight. Our data demonstrate that aspirin produces potent inhibition of direct and indirect COX1-mediated platelet aggregation in healthy adults without diabetes regardless of body weight or mass – suggesting that other mechanisms explain lower preventive efficacy of low-dose aspirin with increasing body weight/mass.

Adherence to Sedation Targets With Weight-Based Propofol and Dexmedetomidine in Patients With Morbid Obesity.

Propofol and dexmedetomidine are routinely used in intensive care units (ICUs). Both are lipophilic, potentially leading to accumulation in adipose tissue. Limited evidence exists on what body weight to utilize in patients with morbid obesity. The purpose of this research was to evaluate the safety and efficacy of weight-based sedation with propofol and dexmedetomidine in ICU patients with morbid obesity. Retrospective review of ICU patients admitted from January 2018 to January 2020 who were sedated for ≥48 hours was performed. The primary outcome was the percentage of time within target sedation during the first 48 hours, stratified by body mass index (BMI) <40 or ≥40 kg/m2. Additional outcomes included adverse events and the infusion rate to achieve target sedation. Data were evaluated using descriptive statistics. A total of 80 patients were analyzed. Patients on propofol with a BMI <40 kg/m2 were in their target Richmond Agitation-Sedation Scale (RASS) 11.7% versus 16.1% with a BMI ≥40 kg/m2 (P = .580). Patients with a BMI <40 kg/m2 on dexmedetomidine were in their target RASS 27.6% versus 10.7% with a BMI ≥40 kg/m2 (P = .053). Body mass index did not significantly alter propofol target sedation attainment. However, patients with morbid obesity on dexmedetomidine demonstrated significantly less time in target sedation. An actual body weight dosing strategy of these drugs did not achieve desired target sedation for those with a BMI ≥40 versus BMI <40 kg/m2. These findings support future research on the optimal sedation dosing strategy in this patient population.