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Summary Thalidomide is a medication that has been in existence for over half a century, and has proven to be useful and effective in severe dermatological conditions. For dermatologists, the ability of thalidomide to reduce the levels of the cytokine tumour necrosis factor-α, along with its immunomodulatory and anti-angiogenic properties, is of great significance, with the added advantage of being an oral medication. Its use is of course strictly monitored, owing to its potential adverse effects (AEs), particularly teratogenicity, with precautions taken to ensure its safe and correct use by both prescriber and patient. In this review, we look at the background and mechanism of action of thalidomide, provide an overview of conditions it can be used for with case examples, explain the potential AEs and monitoring requirements, and discuss future developments.

Through the boost of the natural medicinal market, individuals began to use a variety of organic materials in the marketed herbal preparation. Lagerstroemia speciosa (LS) leaves are known as banaba. People have been using a decoction of LS leaves as antidiabetic. The study aimed to investigate the acute and sub-acute oral toxicity of LS in Sprague-Dawley rats. The acute toxicity was determined by a single oral dose of LS (2000 mg/kg). Therein animal behaviour and mortality rate were observed for 14 days. The LS (200 mg/kg) was given for 28 days daily in the sub-acute study. The body weight, organ weight, food, water intake, biochemical, haematological parameters, and histopathology were studied. The findings of this study showed no mortality or morbidity was found in acute and sub-acute toxicity studies in rats. Additionally, no significant variations were found in the respective weight of organ, haematological and biochemical parameters of treated groups with reference to the control group. Moreover, no visible histological changes were detected in the liver of treated groups with reference to the control. In conclusion, the oral administration of LS did not fabricate any major toxic effect in rats. No toxic consequences were reported during acute and sub-acute toxicity investigations. Overall, LS is a safe, natural bio-actives as studied. Further investigations of cytotoxicity and genotoxicity of the above drug(s) or their combinations may be executed for appreciative safety.

Summary Objective Our objective was to evaluate the absorption of finasteride administered by oral and topical routes for treatment of androgenetic alopecia, by means of computer simulations using the GastroPlus ® software. Material and methods In vivo plasma concentration profile of oral administration of finasteride 1 mg tablets from the literature was used in the software to build a compartmental pharmacokinetic model that was extrapolated to simulate topical administration of finasteride 0.25% solution in the scalp. Results were compared to literature and other drug concentrations (0.1% and 1%) were also predicted. Results Compared to literature data, predictive plasma curve from oral administration of finasteride 1 mg showed good correlation, R2=0.992, and Cmax=4.6769 ng/mL. Simulations of topical administration in the scalp for finasteride 0.25% solution showed good correlation, R2=0.908, and Cmax=0.04325 ng/mL when compared to literature data. Topical administration was also simulated at concentrations 0.1% and 1%, both with low plasma concentrations. Conclusion The results obtained in this study suggest that topical finasteride is a potential treatment for androgenetic alopecia in the concentrations analyzed using computer simulations in GastroPlus ®.

Cypermethrin is a potent pyrethroids insecticide causing different pathological features when exposed to mammal. Vitamins are used as nutrient supplements and in clinical studies as medical intervention in some disease conditions. This study was designed to investigate the possible protective effect of vitamin C and E on Cypermethrin induced nephrotoxicity in wistar albino rats. Twenty-eight (28) wistar albino rats were sorted into four groups of seven rats per groups were used in this study. Group A serves as the control and received distilled water orally. Group B, C and D were administered 25mg/kg body weight cypermethrin orally. Group C and D were treated daily with 40mg/kg body weight vitamin C and 20mg/kg body weight vitamin E respectively by oral administration while group B was left untreated for 14 days. Cypermethrin significantly (P

1. The metabolism and excretion of cetagliptin were investigated in healthy male subjects after a single oral dose of 100mg/50μCi [14C] cetagliptin.2. The mean concentration-time profile of cetagliptin was similar to that of total radioactivity in plasma after oral administration of [14C] cetagliptin in healthy male subjects. Cetagliptin was rapidly absorbed after oral administration. Unchanged cetagliptin was the most abundant radioactive component in all matrices investigated. Approximately 53.13% of plasma AUC of total radioactivity was accounted for by cetagliptin. Each metabolite plasma AUC was not higher than 2.93% of plasma AUC of total radioactivity. By 336 h after administration, 91.68% of the administered radioactivity was excreted, and the cumulative excretion in the urine and feces was 72.88% and 18.81%, respectively. The primary route of excretion of radioactivity was via the kidneys.3. Four metabolites were detected at trace levels, and it involved hydroxylated (M436-1 and M436-3), N- sulfate (M500), and N-carbamoyl glucuronic acid conjugates (M640B) of cetagliptin. These metabolites were detected also in plasma, urine, and feces at low levels, except that metabolite M640B was not detected in feces. All metabolites were observed with < 10% of parent compound systemic exposure after oral administration.

Objectives Research about the effects of magnesium (Mg) supplementation on chronic kidney disease-mineral bone disorder (CKD-MBD) among hemodialysis (HD) patients is controversial. Thus, we conducted a meta-analysis to examine Mg supplementation's effects on CKD-MBD in patients requiring dialysis. Methods The PubMed and EMBASE databases were searched for English language studies up to September 2020. The main indicators of our study were changes in serum Mg, calcium (Ca), phosphate, parathyroid hormone (PTH), and C-reactive protein levels, and carotid intima-media thickness (CIMT) after Mg supplementation. Mg efficacy was evaluated by weighted mean difference (WMD) and confidence intervals (CIs), and subgroup analyses of intervention type and intervention duration were also performed. Results Eight eligible studies comprising 309 HD patients were included in our meta-analysis. Mg supplementation alone produced a negative effect on serum PTH levels (WMD = −236.56; 95% CI −349.71 to −123.41) and CIMT (WMD = −0.18; 95% CI −0.34 to −0.01). A subgroup analysis based on intervention type showed a significant improvement in serum Mg (WMD = 1.08; 95% CI 0.51-1.64) and Ca (WMD = −0.50; 95% CI −0.77 to −0.23) levels when Mg was administered via dialysate and oral medication, respectively. Different intervention durations had no effect on serum Mg levels. Mg supplementation had no significant effect on serum phosphate (WMD = −0.25; 95% CI −0.64 to 0.14) and C-reactive protein levels (WMD = −0.02; 95% CI −2.80 to 2,76). Conclusions Our results showed that Mg supplementation alone could improve CKD-MBD by regulating serum Ca and PTH metabolism and decreasing CIMT among HD patients.

Objective: Based on the expression changes in the TGF-β/ALK5/Smad2/3 signal transduction pathway, the repair of cartilage injury in the rabbit knee joint was investigated and evaluated by oral administration of naringin in combination with acellular dermal matrix implantation. Methods: First, twenty New Zealand white rabbits were randomly divided into five groups: a sham operation group (Sham group), a model group (Mod group), a naringin group (Nar group), an acellular dermal matrix group (ADM group), a naringin ​+ ​acellular dermal matrix group (Nar/ADM group). After the 12th week, the repaired tissues were assessed for histomorphology and repair content of the repaired site by observing the morphological characteristics of articular cartilage. The International Cartilage Repair Society (ICRS)'s macroscopic evaluation of the cartilage repair scale and the quantitative scoring repair effect of the modified O'Driscoll grading system were used as evaluation criteria. In addition, the structure of the rabbit knee joint was evaluated by micro-CT scan, histological staining (H & E staining, Alcian blue staining, Safranin-O staining) and immunohistochemical staining (TGF-β2 immunostaining, TGF-β3 immunostaining, Sox-9 immunostaining). Results: ① The observation of the repair morphology of joint defect tissues showed that the repair effects of the Nar and ADM groups were better than that of the Mod group, and the repair effect of Nar/ADM group was the best (P

Background Skin rash often occurs upon oral administration of amoxicillin in children, due to non-immediate hypersensitivity. However, information on delayed hypersensitivity to amoxicillin is scarce. Moreover, the appropriate diagnostic method and actual diagnostic rate of delayed hypersensitivity to amoxicillin among Japanese children are unclear. We conducted intradermal tests (IDTs) and drug provocation tests (DPTs) and retrospectively investigated the proportion of children with a definitive diagnosis of non-immediate hypersensitivity to amoxicillin. We then evaluated the characteristics of patients with a positive allergic workup. Methods We enrolled children referred for suspected findings of mild or moderate non-immediate hypersensitivity to amoxicillin between August 2018 and March 2020. If the IDT in the delayed phase was negative, DPT with amoxicillin (60–90 mg/kg/day) was performed for 7 days. Non-immediate hypersensitivity to amoxicillin was defined when IDT or DPT was positive. We evaluated the potential of the drug-induced lymphocyte stimulation test (DLST) to reveal hypersensitivity to amoxicillin. Results This study enrolled 27 children. Fourteen children (52%) had hypersensitivity to amoxicillin, of whom 12 had positive IDTs and two had positive DPTs. No differences in age, sex, history of allergic disease, days from oral use to symptom onset, type of rash at symptom onset, generalized rash, and DLST results were observed between the hypersensitivity and non-hypersensitivity groups. Conclusions Examination should be performed for children with mild or moderate reactions because positive cases have no significant features and half of the suspected cases are negative.

BACKGROUND AND OBJECTIVE Benign Prostatic Hyperplasia (BPH) is a prevalent disease among older men caused by abnormal proliferation of the prostatic cells. Findings indicate an association between dyslipidemia and BPH. This study aimed at evaluating the effect of ethanol extract of Sphenostylis stenocarpa seed on the lipid profile of rats with testosterone propionate-induced BPH. MATERIALS AND METHODS A total of 25 male Wistar rats randomized into five groups of five rats each were used. BPH was induced in the rats by subcutaneous injection of testosterone propionate in olive oil for 28 days. The test rats (after BPH induction) were treated with ethanol extract of the plant seed at doses of 200 and 400 mg kg-1 b.wt. The concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triacylglycerol were evaluated on the sera of the rats. RESULTS The BPH control rats (model group) showed a significant (p

Background: Acute Kidney Injury (AKI), a common disease of the urinary system, can be induced by high doses of gentamicin (GM). The renin-angiotensin system exerts a key role in the progression of the AKI since elevated intrarenal levels of Ang II, and ACE activity is found in this condition. However, it is unknown whether oral administration of angiotensin (Ang)-(1-7), a heptapeptide that evokes opposite effects of Ang II, may attenuate the renal injuries induced by gentamicin. Objectives: To evaluate the effects of Ang-(1-7) on GM-induced renal dysfunction in rats. Methods: AKI was induced by subcutaneous administration of GM (80 mg/Kg) for 5 days. Simultaneously, Ang-(1-7) included in hydroxypropyl β-cyclodextrin (HPβCD) was administered by gavage [46 μg/kg HPβCD + 30 μg/kg Ang-(1-7)]. At the end of the treatment period (sixth day), the rats were housed in metabolic cages for renal function evaluation. Thereafter, blood and kidney samples were collected. Results: Ang-(1-7) attenuated the increase of the plasmatic creatinine and proteinuria caused by GM but did not change the glomerular filtration rate nor tubular necrosis. Ang-(1-7) attenuated the increased urinary flow and the fractional excretion of H2O and potassium observed in GM rats but intensified the elevated excretion of sodium in these animals. Morphological analysis showed that Ang-(1-7) also reduced the tubular vacuolization in kidneys from GM rats. Conclusion: Ang-(1-7) promotes selective beneficial effects in renal injuries induced by GM.

BACKGROUND: Despite the exact etiopathogenesis of psoriasis remains unknown, the increasing or decreasing of some trace elements and oxidative stress status are considered to play a role. In this study, the effect of Lactocare R synbiotic on the serum levels of trace elements including Zn, Cu, Mg, Na, Fe, P, Ca, and K in the patients with mild to moderate psoriasis was investigated. METHODS: Sixty-four patients with mild to moderate psoriasis were included. Patients were randomly divided into treatment (n32) and control (n32) groups. The treatment group received Lactocare R and the control group received a placebo (two times daily for 12 weeks). Eight patients from the intervention group and 18 patients from the control group discontinued the study because of the recent COVID-19 condition. For routine trace element analysis, the blood samples were collected from all patients at the baseline as well as week 12 post-treatment. The serum was then isolated and the serum levels of trace elements including Fe, K, Ca, Mg, P, Zn, Na, and Cu were measured using an automatic electrolyte analyzer. For confirmation of the effect of Lactocare R on the alteration of serum levels of trace elements, intra-group analysis was performed at two interval times: baseline and week 12 post-treatment. RESULTS: The serum levels of K, P, and Ca in the placebo group were significantly higher than that of the treatment group at baseline. Serum levels of Zn and Ca were significantly higher in the treatment group compared to the placebo group at week 12 post-treatment. Moreover, a significantly lower serum level of K, P, and Ca in the treatment group at the baseline compared to the placebo group was compensated on week 12 post-treatment. Intra-group analysis in the treatment group showed that the serum levels of Fe, Ca, Mg, P, Zn, and Na was significantly increased at week 12 post-treatment compared to baseline levels. Whereas, intra-group analysis in the control group showed only Ca has a significant difference between baseline and week 12 post-treatment. CONCLUSION: The serum levels of Fe, Zn, P, Mg, Ca, and Na are increased significantly 12 weeks after oral administration of Lactocare R in psoriatic patients. The serum level of Fe and Cu is affected by sex at pre- and post-treatment. This study supports the concept that Lactocare R exerts beneficial effects in the gastrointestinal tract to improve mineral absorption in psoriatic patients.

ObjectiveThe understanding of acceptability of existing dosage forms is limited in most of the world and hinders the development of acceptable, age‐appropriate medicines. The attributes of paediatric medicine acceptability may differ from country to country based on culture, healthcare infrastructure and health policies. This study was designed to map the acceptability of oral medicines in paediatric patients treated in hospital in India.MethodsAn observational, cross-sectional study was conducted in patients aged below 18 years and taking any form of oral medication. Acceptability scores were obtained using CAST–ClinSearch Acceptability Score Test tool.Findings490 patients were recruited and 193 evaluations of different pharmaceutical products available in 20 dosage forms and 7 routes of administration were studied. Oral liquids (50%) and tablets (35%) were the most commonly prescribed and administered forms. Regardless of the therapeutic class and age, the oral liquids were ‘positively accepted’ in infants and toddlers. Acceptability of tablets improved with age and appeared to be generally good from the age of 6.ConclusionThis study indicates the limited progress towards adoption of age-appropriate dosage forms in India and thus impact on the acceptability of existing oral dosage forms. The key challenges posed by the adoption of age-appropriate formulations in India are (1) awareness of importance of appropriate administration and acceptability of medicines to children in India, (2) availability of age-appropriate dosage forms and (3) lack of child-appropriate medicine policies.

We previously reported a 39-year-old man who presented with pulmonary and cerebral Cryptococcus gattii (genotype VGIIa) infection and was successfully treated with liposomal amphotericin B and flucytosine induction therapy. Following induction therapy, oral fluconazole treatment was initiated as consolidation therapy. However, the patient complained of progressively worsening headache, presenting an elevated cerebrospinal fluid (CSF) cell count. The minimum inhibitory concentrations of the CSF isolate were 8 and 0.12 μg/mL for fluconazole and voriconazole, respectively. The oral administration of voriconazole for more than 18 months alleviated his symptoms. Voriconazole might be useful for controlling refractory cases of C. gattii infection.

Aluminum oxide nanoparticles (Al2O3NPs) are one class of widely used nanomaterials. However, the teratogenicity toxicity of Al2O3NPs in mammal remains poorly understood. This study was aimed to evaluate the teratogenicity of Al2O3NPs in Sprague Dawley (SD) rats by gavage and to compare the effects of Al2O3NPs to those of equivalent dose of microscale aluminum oxide (bulk Al2O3). Sixty pregnant rats were randomly divided into 5 groups and treated with 100 and 200 mg/kg body weight (bw) Al2O3NPs (30 nm), 200 mg/kg bulk Al2O3, deionized water (as the negative control), and 300 mg/kg aspirin (as the positive control). Rats were exposed daily by oral gavage from the 7th day of gestation for 10 consecutive days and sacrificed on the 20th day of gestation. Results of the study showed that there were no significant effects of Al2O3NPs on pregnant rats (clinical signs, body weight, food consumption, ovary and uterus weight, number of corpora lutea) and fetuses (body weight, sex, body length, tail length, skeletal and visceral development). Under the experimental conditions of the present study, 10 consecutive days of repeated oral administration of Al2O3NPs at doses of up to 200 mg/kg/day did not induce any treatment-related teratogenicity in SD rats. Accordingly, the NOAEL was determined to be 200 mg/kg Al2O3NPs (106 mg Al/kg bw/day) in rats. The teratogenic effects of Al2O3NPs in rats were comparable to those of the bulk Al2O3 of same doses (200 mg/kg).

Reproductive toxicity is a major challenge associated with aluminum (Al) exposure. Therefore, this study aimed to investigate the effects of zinc oxide nanoparticle (ZnONP) treatment on Al-induced reproductive toxicity in rats. Thirty-two adult male albino rats were allocated into four equal groups as follows: control, AlCl3 orally administered group (100 mg/kg bwt), ZnONPs injected intraperitoneally (i.p.) group (4 mg/kg bwt), and ZnONPs + AlCl3–treated group. The treatment was daily extended for 42 consecutive days. Oral administration of AlCl3 showed an oxidative damage confirmed by an increase in malondialdehyde and nitric oxide levels and superoxide dismutase activity and accompanied by a decrease in glutathione content and catalase activity. Also, AlCl3 administration increased the pro-inflammatory mediator tumor necrosis factor-alpha. Furthermore, significant declines in the levels of serum male reproductive hormones testosterone, luteinizing hormone, and follicle-stimulating hormone in AlCl3-intoxicated rats were noticed. In parallel, severe histopathological alterations were observed in testis tissues. Additionally, the immunohistochemical analysis showed that AlCl3 administration potentiates cell death in the testicular tissue by elevating the immunostaining intensity signal for the pro-apoptotic protein, cysteinyl aspartate specific protease-3 (caspase-3) and a marked depletion in the cell proliferation expression marker, Ki-67, in germinal cells of AlCl3-treated group. On the other hand, the daily i.p. injection to rats with ZnONPs before AlCl3 was found to ameliorate the reproductive toxicity induced by Al administration through reducing the testicular oxidative stress and improving the inflammatory, apoptotic, and reproductive markers as well as histopathological alterations in the testis. These results suggest that ZnONPs could be used as an alternative agent to minimize the reproductive toxicity associated with Al exposure through its antioxidant, anti-inflammatory, anti-apoptotic, and reproductive modulatory activities.

Objetive To evaluate the enterohepatic circulation of 75-Selenium turoselecolic acid (75Se-SeHCAT) during the first 3 h and its correlation with the abdominal retention at the 7th day (AR7), as contribution to the clinical study of biliar acid malabsorption (BAM). Materials and methods 38 patients with chronic diarrhea were retrospectively studied. Acquisition protocol included static abdominal images at 1st, 2nd and 3rd hour and the 7th day after oral administration of the radiopharmaceutical. Images of 1–3 h determined 5 patterns of enterohepatic circulation that, due to their location, were characterized as: 1) gallbladder 2−3 h, 2) gallbladder 3 h, 3) gallbladder-abdomen 2−3 h, 4) abdomen, 5) upper left abdomen. The association of these patterns with the AR7 (Fisher, STATA) were investigated. Patients were classified as Non BAM (AR7 > 15%), mild-BAM (AR7 15−10%), moderate-BAM (AR7 10−5%) or severe-BAM (AR7 Results 19 patients had an AR7 diagnostic of BAM (7 mild-BAM, 5 moderate-BAM, 7 severe-BAM). The pattern “gallbladder at 2−3 h” was statistically associated with Non BAM (p 0,008), while “gallbladder-abdomen at 2−3 h” was correlated with having BAM (p 0,029). Conclusion Variations detected at the abdominal level in images during the first 3 h were associated with changes in intestinal absorption and the incorporation of the radiopharmaceutical into the pool of bile acids, so visual interpretation of the images at 2nd and 3rd hour could be useful in the final assessment of the study.

Diabetes mellitus (DM) is a chronic hyperglycemic that can cause complications in several organs. It could lead glycosylated hemoglobin or HbA1c formation which has ability undergo further changes into Advanced Glycation End Products (AGEs) and stimulate activation of transcription factors such as nuclear factor kappa B (NF-κB). Some studies showed that anthocyanin has antioxidant and anti-inflammatory activity and it has been found Rosa damascene contain high level of anthocyanin. Total anthocyanin content was 0.459 ± 0.003 mg/L. The aim of this study was to investigate inhibitory effect of R. damascena extract on HbA1c levels and NF-κB activation in diabetic rats. Male wistar rats (n=24) were divided into 6 groups as normal control (KN), streptozotocin-induced diabetic control (KP), diabetic treated with R. damascene (P1, P2, P3; 250, 500 and 1000 mg/kg/d respectively) and diabetic treated with metformin (KM; 500 mg/kg/d). This was carried out for 28 days. The inhibition mode of R. damascene extract was examined by measuring HbA1c levels and expression of NFκB by immunohistochemistry. The results showed p values ​​> 0.05 for HbA1c and p < 0.05 for NFκB. From immunohistochemical staining, it seen the expression of NFκB was low in treated group (P1, P2, P3 and KM) compared with KP. Thus, oral administration of R. damascene extract for 28 days could not reduce HbA1c levels, but can supress NFκB expression.

Primary enteroliths associated with Crohn's disease have been considered to be rare and are most likely caused by severe ileal stenosis. Herein, we report the case of a primary enterolith possibly caused by mild jejunal stenosis in a Crohn's disease patient who received oral administration of ursodeoxycholic acid (UDCA). A 62-year-old woman with a 6-year history of Crohn's disease, currently in clinical remission, was on UDCA prescription for liver dysfunction. Magnetic resonance imaging and double-balloon endoscopy, which were performed to examine epigastric pain, revealed mild jejunal stenosis and an enterolith on the oral side. Since it was difficult to remove or crush the enterolith endoscopically, we decided to remove it surgically with the stenotic jejunum. Component analysis revealed that more than 98% of the enterolith was composed of UDCA; subsequently, oral administration of UDCA was discontinued. This case demonstrated that primary enterolith might develop in Crohn's disease patients with mild intestinal stenosis, and oral administration of UDCA can trigger an enterolith in such patients. Therefore, routine follow-up imaging is necessary for early detection. Oral UDCA should be administered with caution for Crohn's disease patients with stenosis of the proximal small intestine.

Purpose Lorlatinib is a third-generation tyrosine kinase inhibitor currently approved for the treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer. This open-label, phase 1, randomized two-sequence, two-treatment, two-period, crossover study investigated the absolute oral bioavailability of lorlatinib in healthy participants. Methods Eligible participants were randomized to receive two treatments in one of two sequences: lorlatinib 100 mg single oral dose followed by lorlatinib 50 mg intravenous (IV) dose, or lorlatinib IV dose followed by lorlatinib oral dose, each with at least a 10-day washout between successive lorlatinib doses. Blood samples for pharmacokinetics were collected for up to 144 hours (h) after dosing. Validated liquid chromatographic-tandem mass spectrometry was used to determine plasma concentrations of lorlatinib and its benzoic acid metabolite PF-06895751. Results In total, 11 participants were enrolled (mean age 37.6 years, all male). The adjusted geometric mean (90% confidence interval) for the absolute oral bioavailability was 80.78% (75.73–86.16%). Using non-compartmental analysis, the estimated arithmetic mean elimination plasma half-life of lorlatinib was 25.5 and 27.0 h after the oral and IV doses, respectively. No deaths, serious adverse events (AEs), or severe AEs were reported, and most treatment-emergent AEs were mild in severity, with two events of transaminase increase of moderate severity. All treatment-emergent AEs were resolved by the end of the study. Conclusion Both oral and IV lorlatinib were well-tolerated in healthy participants and oral lorlatinib is highly bioavailable after oral administration.

Background. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment option for various hematopoietic diseases and certain hereditary diseases. Chronic graft-versus-host disease (cGVHD) has become the main life-threatening complication and cause of death in later stage postallo-HSCT. Current treatment options for cGVHD are limited. Hydrogen gas (H2) has been demonstrated that has antioxidative, anti-inflammatory, and antifibrosis effects. The aim of this study was to confirm whether oral administration hydrogen-rich water exerted therapeutic effects on a scleroderma cGVHD mouse model and tried to explain the mechanism underly it. Methods. A mouse cGVHD model was established by haploidentical bone marrow transplantation. To evaluate therapeutic effects of H2 on cGVHD, survival rate, changes in clinical scores, and skin pathologic characteristics of cGVHD mice were observed. To evaluate its therapeutic mechanism, we detected the expression levels of antioxidative enzymes heme oxygenase-1(HO-1) and NAD (P)H: quinone acceptor oxidoreductase 1(NQO1) in skin homogenates. We also detected the expression level of the apoptotic protein caspase-3 in skin homogenates. Results. 1-month survival rate of cGVHD mice in the hydrogen group reached 93.3%, significantly higher than 66.7% in the nonhydrogen group ( p < 0.05 ). Clinical score of cGVHD mice was improved by hydrogen-rich water at 96 days posttransplantation (2.2 versus 4.5, p < 0.05 ). The skin pathological condition of cGVHD mice was significantly improved by hydrogen-rich water. At 96 days posttransplantation, average skin pathological hematoxylin and eosin (HE) staining score in the hydrogen group was 1.05, which was significantly lower than 3.2 in the nonhydrogen group ( p < 0.01 ). Average Masson staining score was 0.6 point in the hydrogen group, lower than 0.9 point in the nonhydrogen group ( p < 0.05 ). Both the relative expression levels of HO-1 and NQO1 proteins in skin specimens of cGVHD mice in the hydrogen group were lower than that in the nonhydrogen group (2.47 versus 6.21 and 1.83 versus 3.59, p < 0.05 ). The relative expression level of caspase-3 protein in skin specimens of cGVHD mice increased to 7.17 on the 96th day after transplantation, significantly higher than 4.36 in the hydrogen group. Conclusion. In this study, we found that oral hydrogen-rich water improved the survival rate and clinical symptoms of cGVHD mice by antioxidant and antiapoptosis. This study would pave the way for further clinical study, which may provide a new treatment option for cGVHD.

The functional characteristics of Lactobacillus johnsonii BFE6154, first isolated from Maasai traditional fermented milk, were previously identified in vitro, but its cholesterol-lowering properties have not been verified yet. In this study, we investigated the effect of L. johnsonii BFE6154 on cholesterol regulation and the mode of action. Stimulation of Caco-2 intestinal epithelial cells with L. johnsonii BFE6154 downregulated the gene expression of Niemann-Pick C1-like 1 (NPC1L1) through the activation of liver X receptor (LXR). Also, stimulation of HepG2 cells with the metabolites produced by L. johnsonii BFE6154 revealed an increase in the gene expression of low-density lipoprotein receptor (LDLR). Oral administration of L. johnsonii BFE6154 in mice receiving a high-fat and high-cholesterol diet (HFHCD), reduced total cholesterol and low-density lipoprotein-cholesterol (LDL) and increased high-density lipoprotein-cholesterol (HDL) in the blood, compared to the control. Diet-induced hypercholesterolemic mice receiving L. johnsonii BFE6154 showed a suppression of cholesterol absorption under the control of NPC1L1 in the intestine. Furthermore, L. johnsonii BFE6154 consumption ameliorated the hepatic cholesterol level and LDLR expression, which was reduced by HFHCD. These molecular modulations led to the increase of cholesterol excretion and the decrease of cholesterol levels in the feces and liver, respectively. Taken together, these results suggest that L. johnsonii BFE6154 may protect against diet-induced hypercholesterolemia through the regulation of cholesterol metabolism in the intestine and liver.

Metoclopramide is a prokinetic agent used to promote gastrointestinal motility. It is available for intramuscular, intravenous, subcutaneous and oral administration. In June 2020, metoclopramide nasal spray (MNS) 15 mg (administered 30 min before each meal and at bedtime for 2–8 weeks), received FDA-approval for the acute and chronic management of diabetic gastroparesis (DG) in adults. Four studies that evaluated the efficacy and tolerability of MNS in patients with DG were identified, but none evaluated MNS 15 mg. Of the four studies, one found MNS more effective than metoclopramide tablets: per-protocol patients receiving MNS 10 mg and 20 mg experienced a statistically significant reduction in total symptom scores at six weeks, versus metoclopramide 10 mg tablets. In three placebo-controlled 4-week studies, DG symptom improvements seen with MNS 10 mg or 14 mg were statistically insignificant in men but were statistically significant in women. Adverse events of mild-to-moderate severity included headache, cough, nasal discomfort and dysgeusia. Further research is needed to assess the efficacy (e.g., individual and combined symptom scores, hospitalizations due to acute flares), tolerability, pharmacokinetics and cost-effectiveness of MNS 15 mg over 8–12 weeks in patients with DG.

The aim of this article is to consider and support the rationale for prescribing decisions throughout the Parkinson's disease trajectory. The authors will discuss the challenges of managing both motor and non-motor features of Parkinson's disease mindful of potential complications attributable to both progression and medications used. This will include motor fluctuations and impulse control behaviours, which can adversely affect quality of life. The Parkinson's specialist will need to consider a treatment regimen that optimises symptom control while limiting the potential adverse effects of medications. This article will provide an overview of oral medications used throughout the recognised stages of Parkinson's disease.

Finding new, safe strategies to prevent and control rheumatoid arthritis is an urgent task. Bioactive peptides and peptide‐rich protein hydrolyzate represent a new trend in the development of functional foods and nutraceuticals. The resulting tissue hydrolyzate of the chicken embryo (CETH) has been evaluated for acute toxicity and tested against chronic arthritis induced by Freund's full adjuvant (modified Mycobacterium butyricum) in rats. The antiarthritic effect of CETH was studied on the 28th day of the experiment after 2 weeks of oral administration of CETH at doses of 60 and 120 mg/kg body weight. Arthritis was evaluated on the last day of the experiment on the injected animal paw using X‐ray computerized microtomography and histopathology analysis methods. The CETH effect was compared with the non‐steroidal anti‐inflammatory drug diclofenac sodium (5 mg/kg). Oral administration of CETH was accompanied by effective dose‐dependent correction of morphological changes caused by the adjuvant injection. CETH had relatively high recovery effects in terms of parameters for reducing inflammation, inhibition of osteolysis, reduction in the inflammatory reaction of periarticular tissues, and cartilage degeneration. This study presents for the first time that CETH may be a powerful potential nutraceutical agent or bioactive component in the treatment of rheumatoid arthritis., Finding new, safe strategies to prevent and control rheumatoid arthritis is an urgent task. Bioactive peptides and peptide‐rich protein hydrolyzate represent a new trend in the development of functional foods and nutraceuticals. This study presents for the first time that CETH may be a powerful potential nutraceutical agent or bioactive component in the treatment of rheumatoid arthritis.

Objective To compare the therapeutic effect on menopausal hot flashes between acupuncture and Climen so as to provide a new approach to the treatment of this disease. Methods A total of 80 cases in line with inclusion criteria were randomized into a treatment group (treated with acupuncture) and a control group (oral administration with climen), 40 cases in each one. The treatment for 1 month was as 1 course and lasted consecutively for 2 courses. Before and after treatment, the contents of serum estrogen (estradiol, E2) and 5-hydroxytryptamine (HT) and the scores of the attack frequency and severity scale of hot flashes and sweating, domestic modified Kupperman scale and traditional Chinese medicine (TCM) symptom scale were observed, and the clinical therapeutic effect was evaluated in the two groups separately. Results Before treatment, there was no difference in the content of E2 and 5-HT, the score of hot flashes and sweating, Kupperman score and TCM symptom score in the patients between two groups, indicating the comparability (all P > 0.05). Compared with the data before treatment, the contents of serum E2 (treatment group vs control group: 22.24 ± 11.02 vs 33.12 ± 1.01; 22.11 ± 10.19 vs 25.29 ± 2.23) and 5-HT (treatment group vs control group: 96.12 ± 8.21 vs 131.21 ± 30.21; 96.98 ± 7.99 vs 108.29 ± 22.08), the score of hot flashes and sweating (treatment group vs control group: 8.24 ± 1.02 vs 3.12 ± 1.01; 8.11 ± 1.19 vs 5.29 ± 2.23), Kupperman score (treatment group vs control group: 26.12 ± 2.21 vs 11.21 ± 0.21; 26.98 ± 1.99 vs 18.29 ± 2.08) and TCM symptom score (treatment group vs control group: 18.97 ± 3.87 vs 10.12 ± 0.16; 19.01 ± 2.29 vs 15.61 ± 2.89) were statistically different after treatment in the two groups (all P Conclusion Acupuncture effectively reduces Kupperman score and TCM symptom score in the patients and its therapeutic effect is better than climen. Regarding relieving hot flashes symptoms in menopausal patients of kidney yin deficiency and improving in attack frequency and severity of hot flashes and sweating, the effects of acupuncture are superior to Climen. Acupuncture obviously increases the contents of serum E2 and 5-HT.

To observe the clinical efficacy of ‘Tong Du Yun Pi’ (Governor Vessel-unblocking and spleen-promoting) manipulation in treating infantile diarrhea in autumn. Eighty-four kids were divided into a control group and an observation group using the random number table method, with 42 cases in each group. The control group was intervened by oral administration of montmorillonite powder, and the observation group was given additional ‘Tong Du Yun Pi’ pediatric massage (tuina) treatment. After treatment, the traditional Chinese medicine (TCM) symptoms scores, symptom improvement time, clinical efficacy and immune function indicators were compared between the two groups. After treatment, the total effective rate was 95.2% in the observation group versus 76.2% in the control group, and the between-group difference was statistically significant (P

The aim of this work was to evaluate the effectiveness of quercetin addition to the treatment regimen for patients with COVID-19 associated pneumonia. Materials and methods. The effectiveness of two dosage forms of quercetin was studied in 200 patients, who were divided equally into the main and control groups. The main group patients received quercetin in addition to the basic therapy: intravenous drip of Quercetin/Polyvinylirolidone during the first 10 days followed by oral administration of Quercetin/Pectin over the next 10 days. Patients from the control group received only the basic therapy drugs. The study evaluated the dynamics of the disease symptoms (saturation level, respiratory rate, body temperature, cough, general weakness), as well as laboratory markers (C-reactive protein (CRP), ferritin, D-dimer). Results. Two dosage forms of quercetin consistently used in addition to the basic therapy improve pulmonary gas exchange and accelerate the lung function recovery. This is evidenced by a statistically significant majority of patients with positive dynamics in the symptoms of “Saturation level” and “Cough” as well as the meeting a complex indicator of the therapy effectiveness 2 days earlier than in the control group. The treatment regimen applied also helps to stabilize the level of D-dimer in the blood of the main group patients. Conclusions. The use of two dosage forms of quercetin in addition to the basic therapy accelerates the recovery of patients with coronavirus disease associated pneumonia and can help to prevent the progression of COVID-19 associated coagulopathy.

Background: Direct relation between hypercholesterolemia and hyposalivation was suggested. Phytosterols of herbal origin have been used as prophylactic or curative agents against many disorders. Objectives: Evaluate the protective role of Nigella sativa (Ns) versus Lepidium sativum (Ls) on the histological picture of submandibular salivary glands in hypercholesterolemic albino rat; and its immunomodulatory role of nuclear factor kappa B cell (NF-κB) and alpha smooth muscle actin (α-SMA) expression on the tissues. Materials and method: This study was performed with forty male albino rats, divided into four equal groups as follow: Group 1 (n=10): served as negative control, Group 2 (n=10): were fed with hypercholesteremic supplement (HCS) for 8 weeks. Group 3 (n=10): were fed HCS with oral administration of (Ns) seeds for 8 weeks. Group 4 (n=10): were fed HCS with oral administration of (Ls) seeds suspension for 8 weeks. Results: Histological results of submandibular salivary gland in group 2 revealed severe atrophic and degenerative changes in the secretory terminal portions & ducts. In group 3, the tissues appeared with nearly normal histological structures which reflect the beneficial effects of Ns. In group 4, a lesser degree of improvement was noticed with Ls. Quantitative analysis for α-SMA and NF-κB revealed highly statistically significant decrease in group 3 and 4 in comparison with group 2. Conclusion: The immunohistochemical finding confirmed the histological results of the present study that proved the superior protective effects of Ns rather than Ls seeds against hypercholesterolemia on the submandibular salivary glands of albino rats.

The first insulin preparation capable of consistently lowering blood glucose was developed in 1921. But 100 years later, blood glucose control with insulin in people with diabetes is nearly universally suboptimal, with essentially the same molecule still delivered by the same inappropriate subcutaneous injection route. Bypassing this route with oral administration appears to have become technologically feasible, accelerating over the past 50 years, either with packaged insulin peptides or by chemical insulin mimetics. Some of the problems of prospective unregulated absorption of insulin into the circulation from subcutaneous depots might be overcome with glucose-responsive insulins. Approaches to these problems could be modification of the peptide by adducts, or the use of nanoparticles or insulin patches, which deliver insulin according to glucose concentration. Some attention has been paid to targeting insulin preferentially to different organs, either by molecular engineering of insulin, or with adducts. But all these approaches still have problems in even beginning to match the responsiveness of physiological insulin delivery to metabolic requirements, both prandially and basally. As would be expected, for all these technically complex approaches, many examples of abandoned development can be found. Meanwhile, it is becoming possible to change the duration of action of subcutaneous injected insulin analogues to act even more rapidly for meals, and towards weekly insulin for basal administration. The state of the art of all these approaches, and the barriers to success, are reviewed here.

Naringin, a natural flavonoid mainly found in citrus fruit, has been reported to exert a positive effect on improving skeletal muscle health. However, the effects and potential mechanisms of naringin on skeletal muscle fiber switching is still unclear. Here, we discovered that oral administration of naringin increased the low-speed running time, four-limb hanging time, body oxygen consumption in mice, enhanced aerobic enzyme activity, MyHC I expression, and slow-twitch fiber percentage in mice skeletal muscle. By contrast, naringin decreased α-GPDH enzyme activity, MyHC IIb expression, and fast-twitch fiber percentage. Moreover, naringin increased the concentration of serum adiponectin and activated the expression of AdipoR1, APPL1, AMPK, and PGC-1α. Furthermore, by the in vitro experiment and AdipoR1 knockdown, we found that inhibition of the AdipoR1 signaling pathway significantly reduced the effect of naringin on slow-twitch fiber-/fast-twitch fiber-related gene and protein expression. In conclusion, our results indicated that naringin could induce skeletal muscle fiber transition from fast twitch to slow twitch via the AdipoR1 signaling pathway. This study may provide new strategy for improving exercise endurance and slow muscle fiber deficiency-related diseases.

Cyclic glycine-proline (cGP) is a natural nutrient of breast milk and plays a role in regulating the function of insulin-like growth factor-1 (IGF-1). IGF-1 function is essential for post-natal brain development and adult cognitive function. We evaluated the effects of cGP on spatial memory and histological changes in the hippocampus of the adult rats following infancy administration. Infant rats were treated with either cGP or saline between post-natal days 8 and 22 via oral administration to lactating dams. The spatial memory was evaluated between post-natal days 70 and 75 using Morris water maze tests. The changes of capillaries, astrocytes, synaptophysin and glutamate receptor-1 were examined in the CA1 stratum radiatum of the hippocampus. Compared to saline-treated group, cGP-treated group showed higher path efficiency of entry and lower average heading errors to the platform zone. cGP-treated group also showed longer, larger and more astrocytic processes, more capillaries and higher glutamate receptor-1 expression. The rats made less average heading error to the platform zone have more capillaries, larger and longer astrocytic branches. Thus cGP treatment/supplementation during infancy moderately improved adulthood spatial memory. This long-lasting effect of cGP on memory could be mediated via promoting astrocytic plasticity, vascularization and glutamate trafficking. Therefore, cGP may have a role in regulating IGF-1 function during brain development.

The aim of this work is to study the functional features of the multifunctional enzyme of the carbohydrate metabolism, malate dehydrogenase (MDH), in normal rats, rats with alloxan-induced diabetes, and in animals with a pathology which were orally given the alcohol extract of wormwood. It also investigated the isolation of the enzyme using ion exchange chromatography. The induction of experimental diabetes was carried out by a single intraperitoneal injection of 5% alloxan solution to Wistar white male laboratory rats (Rattus norvegicus). After the signs of diabetes appeared, all rats were divided into 3 groups: control animals (no injections of alloxan), the “diabetes” group (animals with signs of diabetes), and the “diabetes + wormwood extract (WE)” group (rats with increased glucose levels in blood that were given alcohol extract of wormwood instead of water). The comparison of the specific activity of MDH from hepatocytes of livers of the rats from the control group subjected to alloxan diabetes and animals with a pathology which were given the wormwood extract, showed that under the conditions of induced diabetes, the rate of MDH functioning increases, while oral administration of the wormwood extract reduced the studied parameter to normal values. A purification of malate dehydrogenase was carried out to resolve the issue regarding the activation of certain metabolic processes associated with malate dehydrogenase activity in case of alloxan-induced diabetes. The study showed that in comparison with the control animals, whose hepatocytes contained two MDH2 and MDH1 isoforms with a specific activity of 39.7 U/mg protein and 48.0 U/mg protein and the purification degree of 99.2 and 120.0, respectively, the animals with experimental diabetes also had an additional isoform of MDG3 with a specific activity of 38 U/mg protein and the degree of purification of 47.5. Two MDH isoforms with a specific activity of 72.08 and 60.5 U/mg protein and the degree of purification of 182.0 and 152.2, respectively, were characteristic of the group of rats that were orally administered a wormwood extract, which was consistent with the trends characteristic of malate dehydrogenase isoenzymes from the control group of animals. Thus, the use of 4-stage purification made it possible to obtain highly purified preparations of MDH isoforms from rat liver with alloxan-induced diabetes. The increase in activity and the appearance of a new isoform of MDH in the liver of diabetic rats confirm the possibility of the participation of the malate dehydrogenase enzyme system in the adaptive response of the organism under stress conditions. The results of the study indicate that a wormwood extract has a hypoglycemic effect, which is manifested in a noticeable decrease in the concentration of glucose in the blood of rats with alloxan-induced diabetes and in blocking the formation of an additional MDH isoform in animals with experimental diabetes.

Several studies on the potential adverse effects of aluminum oxide nanoparticles (Al2O3NPs) have reported conflicting results. The present study investigated the potential adverse effects of Al2O3NPs in Sprague–Dawley rats following 28-day repeated oral administration. In addition, we aimed to determine the target organ and no-observed-adverse-effect level (NOAEL) of Al2O3NPs. Al2O3NPs was administered once daily by gavage to male and female rats at dose levels of 0, 500, and 1000 mg/kg/day for 28 days. There were no treatment-related adverse effects as indicated by the clinical signs, body weight, food consumption, urinalysis, ophthalmology, hematology, serum biochemistry, gross pathology, organ weight, and histopathology at all the tested doses. Under the experimental conditions of the present study, 28-day repeated oral administration of Al2O3NPs at doses of up to 1000 mg/kg/day did not induce any treatment-related systemic toxicity in male and female rats. The NOAEL of Al2O3NPs was set at 1000 mg/kg/day in both male and female rats and no target organs were identified.

Rebamipide (RBM) is known to have a specific absorption window in the upper GI tract. However, there have been no in vivo studies reporting the regional absorption of RBM, which may lead to misjudgment in formulation development considering the many other physiological factors involved in oral absorption. Therefore, this study aimed to assess the regional absorption of RBM. Barium sulfate was incorporated into RBM-sustained release (SR) tablets as a radiopaque marker and the location of RBM-SR tablets was monitored using X-ray imaging after oral administration of RBM-SR tablets in Beagle dogs. Based on the gastric residence time (GRT) of RBM-SR tablets, dogs were divided into two groups: GRTlow for 0.25 and 1.5 h and GRThigh for 3 and 5 h. GRThigh had significantly delayed time to reach peak plasma concentration (Tmax), longer mean residence time (MRT), and higher area under the plasma concentration–time curve from time zero to the last observation time point (AUClast) than GRTlow, which indicates the presence of an absorption window in the upper GI tract. This study, for the first time, reports on the regional absorption of RBM. The findings of this study may be useful for developing RBM-SR formulations.

Renoprotection is a system of measures for primarily pharmacological control, contributing to the continued preservation of renal function. When choosing renoprotection tactics, it is necessary to consider not only the estimated GFR (using the EPI formula), but also a functional renal reserve. The method of determining the renal reserve with oral administration of 0.45–0.50% sodium chloride solution at the rate of 0.5 % of body weight is considered to be physiologically substantiated. The renal reserve determining based on this technique as a routine method for examining nephrological patients provides additional information not only on the number of functioning nephrons, but also on their condition. A differentiated approach to prescribing renoprotective agents has been proposed, taking into account the stage of the disease and the functional renal reserve for maximum preservation of functioning nephrons.

Background: The aim was to determine the effect of feeding on chiral inversion of Ibuprofen isomers. Method: Six healthy volunteers participated in a two-treatment crossover study where a single dose of Ibuprofen racemate was given. One stage consisted in an 8-hour interval of fasting, while in the other, the drug was administered with a solution of saccharose and a standard food intake regimen was implemented.

Chengxin Li,&ast; Jiejiu Lu,&ast; Siru Zhou, Yinyi Wei, Chunle Lv, Taotao Liu, Yun Wu, Dongni Wu, Jianying Qi, Rongda Cai Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Taotao LiuDepartment of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi Province, People’s Republic of ChinaTel +86 7715356789Email liutaotao@gxmu.edu.cnPurpose: To analyze factors influencing tacrolimus (TAC) trough concentration (C0) in β-thalassemia major (β-TM) pediatric patients after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and to investigate the effects of genotype polymorphism and drug-drug interactions on TAC trough concentration in children with β-TM. Furthermore, to analyze the correlation between TAC C0 and efficacy and adverse reactions.Patients and Methods: Prospectively collection of demographic information and details of combined treatment of patients with β-TM receiving HSCT, and genotypes of CYP3A4, CYP3A5, and ABCB1 (rs1045642, rs1128503, rs2032582) were obtained for each patient. Univariate analysis and multiple linear regression analysis were used to investigate influencing factors on TAC C0. The impact of different genotypes and the co-administration of azole antifungal drugs on β-TM patients receiving TAC were evaluated, together with the correlation between acute graft-versus-host disease (aGVHD), infection, and liver injury of TAC C0.Results: A total of 46 patients with 587 concentration data were included. The multiple linear regression results showed that the patient’s sex, weight, postoperative time, hemoglobin, platelet count, serum cystatin C, and combined voriconazole were independent influencing factors of the infusion trough concentration/daily dose, C0/Div. Age, body surface area, postoperative time, co-administration of voriconazole, and CYP3A4&ast;18B are independent influencing factors of C0/Dpo. Group comparisons showed that voriconazole can affect TAC C0 administered intravenously (IV) and orally in β-TM pediatric patients, while patient genotype can affect TAC C0 during oral administration. TAC C0 does not correlate with aGVHD or liver injury, but infection may be associated with TAC C0.Conclusion: The concentration of TAC should be closely monitored when co-administered with voriconazole. It is worth considering that the influence of genotype on the trough concentration of oral TAC and individualized drug administration warrant investigation. Finally, this study indicated that C0 is not suitable as an indicator of the efficacy of TAC.Keywords: β-thalassemia major, allogeneic hematopoietic stem cell transplantation, tacrolimus, trough concentration

Introduction There have been no prospective clinical studies investigating adherence and tolerability of HIV post-exposure prophylaxis (PEP) in China. Tolerability, adherence, and transmitted drug resistance are concerns, especially when single-tablet regimen (STR) usage is low. The present study aimed to explore the safety, tolerability, and adherence of regimens containing albuvirtide (ABT) compared with recommended non-STR antiretrovirals for HIV PEP. Methods This was a prospective, open-label, multicenter cohort study. The subjects were stratified into 3 groups based on their preference: ABT + Dolutegravir (DTG) (Group 1), ABT + Tenofovir disoproxil fumarate (TDF) + Lamivudine (3TC) (Group 2), and DTG + TDF + 3TC (Group 3). All enrolled subjects received PEP within 72 h after exposure and continued for 28 days, and were followed-up for 12 weeks. Results A total of 330 participants were enrolled in the three groups. Most participants were male (87.2%). Sexual contact was the most frequent mode of exposure (91.9%). The average time from exposure to treatment was 26.8 ± 19.5 h. There were no statistically significant differences between the three study groups with respect to completion of oral medication at 28 days. The 28-day completion rate was shown to be significantly higher with ABT versus oral (88.9% vs. 64.0%; p

The first-generation taxanes (including paclitaxel and docetaxel) are widely used for the treatment of various cancers in clinical settings. In the past decade, a series of new-generation taxanes have been developed which are effective in the inhibition of tumor resistance. However, intravenous (i.v.) infusion is still the only route of administration, and may result in serious adverse reactions with respect to the utilization of Cremophor EL or Tween-80 as solvent. Besides, the dosing schedule is also limited. Therefore, oral administration of taxanes is urgently needed to avoid the adverse reactionss and increase dosing frequency. In this review, we first outlined the discovery and development of taxane-based anticancer agents. Furthermore, we summarized the research progress on the oral formulations of taxanes and proposed some thoughts on the future development of oral taxane formulations.

Acute and subacute toxicity tests were undertaken on a novel galacto-oligosaccharide (GOS) produced from lactose by β-galactosidase derived from Bacillus circulans. Toxicity was evaluated by single dose oral administration (5,000 mg/kg) and was repeated at day 28 (1,000 mg/kg) in male and female Sprague-Dawley rats. In acute toxicity tests, the protein levels of male rats administered GOS showed a significant difference from controls, but remained within the normal range. There were no GOS-related changes in clinical symptoms, weight, food intake, hematology, blood chemistry, relative organ weight, or severe pathology in rats treated with GOS compared with controls. The no observed adverse effect level of GOS was at least 1,000 mg/kg/d in both male and female rats. Bovine-specific genes were not detected in GOS 70%-based products (NeoGOS-P70, NeoGOS-L70, and organic GOS), indirectly showing the absence of an allergen and that products containing GOS 70% are non-toxic and allergen-free.

In this study, we found that the reduction in muscle sympathetic nerve activity at the onset of static handgrip exercise was blunted following GABAA receptor activation with oral administration of diazepam in young, healthy individuals. The present findings provide novel insight into neural circuitry mechanisms controlling muscle sympathetic outflow during exercise in humans.

The aim of this study was to make animal dyslipidemia models in Sprague Dawley strains induced by a high fat goat diet formula as hypercholesterol feed for two months. The experimental animal used in this study was 30 male rats (Rattus norvegicus strain Sprague Dawley) with an age of 2-3 months with an average body weight of 150g. Animal models are divided into two groups consisting of a control group without additional diet and dyslipidemia group given food consumption goat hypercholesterolemia with high-fat diet formula orally every day for two months. Physiological characteristics of dyslipidemia SD rats had higher body weight, increased food consumption and fecal weight, and decreased water intake and urine volume than the control group. Total cholesterol, triglyceride, and LDL-cholesterol levels increased, while HDL-cholesterol levels did not change in the dyslipidemia rats group compared to the control group. The conclusion of this study indicated that the hypercholesterol diet formula with a high composition of goat fat was successfully induced the SD rats to become dyslipidemia model rat with specific hypercholerol characteristics.

The gut microbiome plays significant role in the function and integrity of the gastrointestinal tract. They also maintain immune homeostasis and host energy metabolism. The metabolic products of these intestinal microbes can alter carbohydrate metabolism, nutrient absorption and reduce appetite to promote healthy lifestyle. Intestinal disbiosis observed in metabolic disorders like obesity and diabetes. Restoration of dysbiosed gut microbiome through oral administration of probiotics that may have profound health effect in diabetes. In case of diabetes, reports postulated impaired level of incretin, therefore we explored the effect of oral administration of probiotic bacteria Lactobacillus casei NCDC 017 (LC017) and Bifidobacterium bifidum NCDC 231 (BB231) alone and in combination on secretion of incretin hormones such as glucagon like peptide-1 and glucose dependent insulinotropic polypeptide. Thirty six male Wistar rats were randomly divided into six groups and diabetes was induced by single dose of streptozotocin (50 mg/kg body weight) in experimental rats intraperitonially except a group of healthy rats. The diabetic rats were daily administered orally with single dose (~107cfu/ml) of LC017 and BB231 alone and in combination for 28 days. Also, one group of diabetic rats was treated with an anti-diabetic drug, acarbose (10mg/kg body weight) and used a standard control. The change in body weight, sucrose tolerance test, GLP-1, GIP level in serum and GLP-1 level in different part of intestine were observed. The results have shown reduction in body weight in diabetic rats as compared to non-diabetic rats but improved after treatment of probiotic bacteria. Administration of LC017 and BB231 significantly improved GLP-1 and GIP level which were initially impaired in diabetic rats and their combination significantly decreased glucose level in sucrose tolerance test. This study indicated that LC017 and BB231 have significant hypoglycaemic potential in diabetic rats by increasing GLP-1 and GIP level. These findings offered a base for the use of LC017 and BB231 for improvement and treatment of diabetes.

Aims We report population pharmacokinetic (popPK) and exposure-response (E-R) analyses for efficacy (induced amenorrhoea [IA]) and safety (unbound oestradiol [E2] concentrations) of the selective progesterone receptor modulator vilaprisan. Results were used to inform the dose for the Phase 3 programme in patients with uterine fibroids. Methods A popPK model was developed using data from Phase 1 and 2 studies (including ASTEROID 1 and 2). The relationship between vilaprisan exposure (steady-state AUC) and IA after oral administration of 0.5, 1, 2 or 4 mg/day over 3 months was analysed in ASTEROID 1 using logistic regression and qualified in ASTEROID 2 by comparing simulated and observed probability for IA after 2 mg/day. The exposure-E2 relationship was analysed visually. Results Vilaprisan clearance was 22.7% lower in obese vs non-obese patients. The E-R relationship for IA in ASTEROID 1 was steep and consistent with ASTEROID 2, with a maximum probability (Pmax ) of 59% (95% CI: 49-68%). The exposure at which 50% of Pmax is obtained was 36.9 μg*h/L (95% CI: 27.7-48.7 μg*h/L). Simulations showed that 36% of the patients will be below 90% of Pmax for IA after 1 mg/day compared to 2% after 2 mg/day. E2 levels tended to decrease with increasing exposure. While E2 levels remained largely within the physiologic follicular phase range, the clinical relevance of this decrease will be evaluated in long-term studies. Conclusions A 2 mg/day dose was selected for Phase 3 as E-R analyses show this dose results in a close to maximum probability for IA, without any safety concerns noted.

Background: Osteoarthritis is the leading cause of chronic disability affecting more than 80% of people over the age of 55. Several treatment options are there for early Osteoarthritis (OA) knee, like- rest, ice, brace, NSAIDs, intra-articular corticosteroid, Intra-Articular Hyaluronic Acid (IAHA), and intra-articular platelet-rich plasma (PRP) injection. Growth factors in PRP (PDGF, IGF, VEGF) promote matrix synthesis, cell growth, and migration, thus facilitating protein transcription. Several studies regarding PRP injection in the management of OA knee support this line of management without any documented complications of PRP at the knee joint. Case Report: We report 4 cases of acute inflammation related to PRP injection for the treatment of OA knee. Two patients developed mild inflammation which was treated with oral medication on an outpatient basis. Another two patients developed moderate to severe inflammation which warranted surgical intervention. Conclusion: Intraarticular PRP injection has been reported in the literature as a successful modality of treatment in OA knee without any significant adverse effect. We are reporting four cases of adverse events following intraarticular PRP injection. Two cases were mild inflammations while the other two were moderate to severe. All four patients recovered and the outcome was satisfactory compared to the preinjection status. The exact cause for the reaction after PRP injection in the knee is not known. Further study is needed for the cause of the inflammatory reaction. Keywords: PRP, OA Knee, Inflammation.

The prevalence of vitamin В12deficiency is about 3—16% in the general population, while in older people, it ranges from 10 to 20%. An increase in the proportion of people on reduced-calorie diets, the widespread use of drugs that can result in vitamin В12deficiency, an increase in life expectancy, on the one hand, a variety of clinical manifestations and the lack of precise algorithms for laboratory diagnostics, on the other hand, suggest that the number of patients with vitamin В12deficiency is significantly higher. Vitamin В12can be absorbed by passive diffusion, regardless of intrinsic factor and other underlying causes of the deficiency. The presence of an additional route of absorption brings in new expectations for the oral administration of cyanocobalamin in therapeutic doses. Comparative clinical trials of the use of cyanocobalamin have shown that the oral route of administration is as effective as the parenteral. Considering the need for long-term, and in some cases — life-long, use of the drug, there is a need to develop dosage regimens for oral administration comparable in effectiveness to parenteral administration. The use of functional vitamin В12deficiency biomarkers, such as vitamin В12levels, cholotranscobalamin, methylmalonic acid, homocysteine, made it possible to establish that a daily dose of 1000 mkg is the most effective, which at the initial stage is as efficient as intramuscular administration. In some circumstances, maintenance therapy (intramuscularly at a dose of 1 mg/month) was more effective; thus, a differentiated approach scheme to determining the maintenance oral dose was proposed, depending on the result obtained at the initial stage of therapy. Comparative studies covering the entire spectrum from the recommended dietary allowance to the dose commonly used for cobalamin injections have shown that an oral daily dose of 1000 mcg of cyanocobalamin normalizes serum vitamin В12levels and causes an 80—90% decrease in plasma methylmalonic acid concentration from the assumed maximum value. The oral route of administration provides a higher patient treatment adherence.

Scoparia dulcis (Linn) is a widespread herbal medicine; it bears an enormous number of pharmacological activities. The present study was undertaken to find out the chronic toxicity profile of oral administration of Scoparia dulcis ethanol leaf extract (SDELE) on the liver and the kidney of wistar rats. The animals were grouped into four and administered varying doses of SDELE (100 mg/kg, 200 mg/kg, 400 mg/kg body weight and 0.2 ml distilled water respectively) for a period of fourteen weeks (100 days). The acute toxicity, body weight, relative organ weight, hematological parameters, biochemical markers for liver and kidney damage were monitored and histopathology of the liver and kidney of the rat were carried out. The LD50 of SDELE was found to be 1131 mg/kg body weight. There was a significant (p0.05) in the relative weight of the organs. There was also a significant increase (p0.05) in any of the parameters studied in the group administered 100 mg/kg body weight dose when compared with the controlled group. Ethanol leaf extracts of Scoparia dulcis showed hepatotoxic and nephrotoxic tendencies and should be used with caution especially when employed in the treatment of chronic diseases

We report a case of mesenteric phlebosclerosis (MP) in a woman in her 50s who had been taking Kamishoyosan for 13 years. Colonoscopic findings 13 years after the start of oral administration were nonspecific, with decreased vascular permeability and redness of the mucosa. The extent of the lesion was initially from the cecum to the ascending colon but expanded over time to the transverse colon. In colon biopsies, there was a remarkable deposition of collagen fibers around the small vessels in the lamina propria of the cecum or the ascending colon over time, and the specific lesions expanded to the transverse colon. The deposition of collagen fibers around the vessels in the lamina propria was already present when the total oral dose of the Sanshishi component was low. In this valuable case of MP, changes after the start of oral administration of Kamishoyosan could be followed over time via endoscopy and biopsy.

18F-FDG PET myocardial metabolic imaging (MMI) is sometimes uninterpretable due to background activity from uncontrolled glucose homeostasis in diabetic mellitus (DM) patients. Trimetazidine is an oral medication that promotes the transformation of myocardial energy supply from free fatty acids to glucose. We aimed to investigate the feasibility and application of trimetazidine in 18F-FDG PET MMI of DM patients. With DM patients exhibiting severe coronary artery disease (CAD) symptoms serving as self-controls, the effects of trimetazidine on PET MMI image quality, myocardial viability assessment, quantitative analytical parameters, and 18F-FDG uptake of different myocardial segments were elucidated. The image quality of 18F-FDG MMI was graded visually as good, moderate, and uninterpretable. After trimetazidine, grades of good, moderate, and uninterpretable were observed in 14 (60.9%), 8 (34.8%), and 1 (4.3%) patients, respectively, and in 4 (17.4%), 15 (65.2%), 4 (17.4%) patients without trimetazidine. The myocardial SUV and myocardial to blood pool SUV ratio (M/B ratio) were significantly higher after trimetazidine administration than those before (3.11 ± 1.07 vs 2.32 ± 1.00, 2.67 ± 1.41 vs 1.81 ± 0.75, P all < 0.01). 6 (3, 7) viable myocardium segments were detected with a mismatch score of 10 (6, 17) after trimetazidine, significantly higher than those before trimetazidine [5 (2, 7) and 8 (2, 17), P < 0.05]. Meanwhile, the 18F-FDG uptake in myocardial segments with decreased and normal perfusion showed different ranges of increase (by 15.30%-57.77%). Trimetazidine is feasible and effective in DM patients with severe CAD before 18F-FDG PET MMI, which can significantly improve the image quality and increase the number of viable myocardium segments detected. The study was registered in the Chinese Clinical Trial Registry (ChiCTR2000038559).