Protection by Chinese herbs against Doxorubicin-induced focal and segmental glomerulosclerosis in rats

The objective of this study was to evaluate the efficacy of Chinese herbs on Doxorubicin-induced focal and segmental glomerulosclerosis (FSGS) in rats. Twenty age-matched male Wistar rats were divided into two groups: group A (n = 10) given only water ad libitum served as the control group and group B (n = 10) was given Chinese herbs (40 ml/kg with drug concentration 1.75 g/ml) beginning at day zero. All rats were administered doxorubicin (7 mg/kg) intravenously. All the rats were placed in metabolic cages at day 0, 7, 14, 21, and 28, and daily proteinuria was measured. At day 28, the animals were killed by cervical dislocation, followed by immediate organ collection for histologic analysis of kidneys; blood was collected by tail vein and cardiac puncture (at day 28) for the measurement of serum albumin. Body weight (BW) and food intake were recorded. The rats in groups A and B demonstrated severe susceptibility to doxorubicin injection with the onset of proteinuria (80-100 mg/24h) at day 7. The rats in group B were partly resistant to doxorubicin nephropathy with decreasing proteinuria and increasing serum albumin compared with group A (p < 0.05). All 10 rats in group A developed at least 5% glomerulosclerosis with tubular casts at day 28. In contrast, the rats in group B developed less severe histologic renal disease. The difference in histologic scores between the two groups were significant at day 28 (12 in group B vs. 20 in group A, p = 0.002). Food intake of Group B animals progressively increased to reach 67-73% of those observed before the doxorubicin administration with 28-43% in Group A. After the 4-wk experimental period, BW in Group A decreased more significantly than that in Group B (-20 +/- 3 and -16 +/- 1%, respectively, p = 0.035, paired T test). Chinese herbs seem to reduce proteinuria and attenuate renal histologic severity in rats with doxorubicin-induced FSGS and may offer an alternative to the treatment of FSGS.     

Effect of hydroxyapatite porosity on growth and differentiation of human osteoblast-like cells

To study whether hydroxyapatite (HA) porosity can influence its osteoconductive properties, cell adhesion, proliferation and differentiation were compared in human osteoblast-like cells grown on HA disks of different porosity (A = 20%, B = 40%, C = 60%). Human osteoblast-like cells were isolated and characterized. Proliferation rate and alkaline phosphatase (ALP) activity were assessed at 3, 7, 15, 21, and 28 days. Type I collagen and osteonectin production were demonstrated with fluorescence microscopy and osteoblast adhesion studied at 7 and 21 days by scanning electron microscopic analysis. Cell growth on HA was three- to six-fold lower than on polystyrene control disks. At 28 days, 2141 (±350) cells/well grew on the most porous disks (Group C), with highly significant differences from controls (p < 0.005). The ALP production was 2–3 fold lower on HA than on plastic. In the Group C the mean ALP activity was of 2.95 (±0.07) UI/well after 28 days, higher than in the other two groups. At 21 and 28 days, proliferation rate and ALP activity on the three HA cultures were significantly different (p < 0.05). A decrease in cell population and increased ALP activity were observed on the most porous material, and high proliferation and poor differentiation rates on the less porous disks.     

A Composite Index of Compliance for Chronic In‐Center Hemodialysis Patients

We developed a composite compliance index as the sum of the compliance scores for interdialytic weight gain (IDWG), pre‐dialysis serum potassium and phosphorus concentrations (each scored from zero to 3, with 3 indicating the poorest compliance), and skipping hemodialysis sessions (scored from zero to 9, with 9 indicating the poorest compliance). We used this composite score to prospectively evaluate compliance in 25 prevalent hemodialysis patients over a period of 1 year. We then followed these patients for another 3.5 years. The patients studied were divided into two groups: group A (poor compliance) consisted of 9 subjects with composite score ≥ 9 (13.2 ± 3.2); group B (better compliance) consisted of 16 subjects with composite score < 9 (4.7 ± 1.8). Age, duration of hemodialysis, and frequency of diabetes mellitus did not differ between the groups. Group A contained higher fractions of subjects with history of alcoholism (66.7% vs 12.5%, p = 0.010), other substance addiction (44.4% vs 0%, p = 0.010), and severe psychosocial problems (88.9% vs 18.8%, p = 0.002). Mean survival from the beginning of observation, estimated by actuarial life‐table survival analysis, was 1.19 years in group A and 2.60 years in group B (p = 0.0265). A composite compliance index incorporating domains indicating adherence to diet, medications, and dialysis schedule identified other behavioral problems in poorly compliant patients. Hemodialysis patients characterized by this composite index as poorly compliant had shortened survival.     

Inhibitory effect of ketoconazole and voriconazole on the pharmacokinetics of carvedilol in rats

The aim of this study was to investigate the effect of orally administered ketoconazole and voriconazole on the pharmacokinetics of carvedilol and its metabolites in rats. Fifteen healthy male Sprague–Dawley (SD) rats were randomly divided into three groups: A group (30?mg/kg ketoconazole), B group (30?mg/kg voriconazole) and C group (control group). A single dose of carvedilol was administered orally 30?min after administration of ketoconazole and voriconazole. Carvedilol and its metabolites plasma levels were measured by ultra-high performance liquid chromatography-mass spectrometry method (UPLC–MS/MS), and pharmacokinetic parameters were calculated by DAS 3.0 software. The co-administrated with ketoconazole could significantly increase the maximal plasma concentration (C_max) and area under the curve (AUC) of carvedilol (p?C_max of its three metabolites 4′-hydroxyphenyl carvedilol (4′-HPC), 5′-hydroxyphenyl carvedilol (5′-HPC) and o-desmethyl carvedilol (o-DMC) decreased drastically by 39.4% (p?p?p?T_max of carvedilol and o-DMC increased, and the C_max of 5′-HPC decreased by 27.7% (p?相似文献   

Repair of experimental Achilles tenotomy with porcine renal capsule material in a rat model

Porcine small intestinal submucosa (SIS) is a collagenous acellular matrix which has found substantial utility as a tissue growth scaffold. In the present study, the utility of porcine renal capsule matrix (RCM) was compared to SIS in a rat Achilles tenotomy repair model. Groups of rats underwent surgical tenotomy followed by either no repair, repair with a SIS graft, or repair with a RCM graft. The weight-bearing ability of the manipulated limb was evaluated for 10 days following surgery using a subjective scale. Tenotomy sites sampled 28 days after surgery were numerically graded for degree of histologic change. There were no statistically significant differences between groups with respect to return to weight-bearing ability (p ≥ 0.05) or degree of histologic change (p ≥ 0.001); however, a non-significant trend suggested that rats treated with SIS or RCM experienced a faster return to limb function than untreated rats, and RCM-treated rats had slightly higher scores for degree of histologic change, suggesting a more rapid repair of the tenotomy site than in SIS-treated or untreated rats. The harvested tenotomy sites in all treatment groups were characterized by marked fibroplasia and presence of macrophages. Remnants of SIS surrounded by macrophages and multi-nucleated giant cells were still present in some rats, however remnants of RCM were not observed, suggesting more rapid incorporation of RCM. The results show that RCM is equivalent to SIS as a material for repair of Achilles tendon injury and merits further study in other tendon injury models.     

Repair of goat tibial defects with bone marrow stromal cells and β-tricalcium phosphate

Tissue engineering techniques have been proven effective in bone regeneration and repairing load-bearing bone defects. Previous studies, however, have heretofore been limited to the use of slowdegradable or natural biomaterials as scaffolds. There are, however, no reports on using biodegradable, synthetic beta-tricalcium phosphate (β-TCP) as scaffolds to repair weight-bearing bone defects in large animals. In the present study, highly porous β-TCP scaffolds prepared by the polymeric sponge method were used to repair goat tibial defects. Fifteen goats were randomly assigned to one of three groups, and a 26 mm-long defect at the middle part of the right tibia in each goat was created. In Group A (six goats), a porous β-TCP ceramic cylinder that had been loaded with osteogenically induced autologous bone marrow stromal cells (BMSCs) was implanted in the defect of each animal. In Group B (six goats), the same β-TCP ceramic cylinder without any cells loaded was placed in the defect. In Group C (three goats), the defect was left untreated. In Group A, bony union can be observed by gross view, X-ray and micro-computed tomography (Micro-CT) detection, and histological observation at 32 weeks post-implantation. The implanted β-TCP scaffolds were almost completely replaced by tissue-engineered bone. Bone mineral density in the repaired area of Group A was significantly higher (p < 0.05) than that of Group B, in which scant new bone was formed in each defect and the β-TCP hadn’t been completely resorbed at 32 weeks. Moreover, the tissue-engineered bone of Group A had similar biomechanical properties as that of the normal left tibia in terms of bending strength and Young’s modulus (p > 0.05). In Group C, little or no new bone was formed, and non-union occurred, showing that the 26 mm segmental defect of the goat tibia was critical sized at 32 weeks. Thus, it can be concluded that the mechanical properties of the BMSCs/β-TCP composites could be much improved via tissue engineering approach and β-TCP might be used to repair the weight-bearing segmental defects of goat tibias. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Effects of elastin-derived peptide on Achilles' tendon healing: An experimental study

Different matrix macromolecules modulate the tendon healing process. Elastin contains sequences which exhibit chemotactic activity both in vitro and in vivo. We analyzed the effects of synthetic elastin-derived peptide Val-Gly-Val-Ala-Pro-Gly suspended in a gel solution on the healing process of Achilles' tendon in a rat model. A total tenotomy at the middle 3rd was performed in 32 rats. During the suture repair the gel with (Group A) or without (Group B) the elastin-derived peptide was applied to the tendon stumps. Four animals for each period and group were killed at 10, 30, 60 and 90 days after surgery. The scar tissue was processed for histochemical, immuno-histochemical and morphometric analysis. An improved healing process with increase in cellularity and vascularity, especially at the early stage of the Achilles' tendon healing process was observed in Group A compared to Group B. The fiber alignment was also positively influenced by the factor. Immunolabeling with HAM 56 and lisozyme revealed a stronger reaction for the presence of monocyte/macrophage in Group A vs Group B especially in early stages. Chondral metaplasia and endochondral ossification occurred in the healed tissue of both group at 60 and 90 days.     

Co-delivery of hydrophilic and hydrophobic drugs by micelles: a new approach using drug conjugated PEG–PCLNanoparticles

Co-delivery strategy has been proposed to minimize the amount of each drug and to achieve the synergistic effect for cancer therapies. A conjugate of the antitumor drug, doxorubicin, with diblock methoxy poly (ethylene glycol)-poly caprolactone (mPEG-PCL) copolymer was synthesized by the reaction of mPEG–PCL copolymer with doxorubicin in the presence of p-nitrophenylchloroformate. The conjugated copolymer was characterized in vitro by ¹H-NMR, FTIR, DSC and GPC techniques. Then, the doxorubicin conjugated mPEG–PCL(DOX–mPEG-PCL) was self-assembled into micelles in the presence of curcumin in aqueous solution. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM).The encapsulation efficiency of doxorubicin and curcumin were 82.31?±?3.32 and 78.15?±?3.14%, respectively. The results revealed that the micelles formed by the DOX–mPEG-PCL with and without curcumin have spherical structure with average size of 116 and 134?nm respectively. The release behavior of curcumin and doxorubicin loaded to micelles were investigated in a different media. The release rate of micelles consisted of the conjugated copolymer was pH dependent as it was higher at lower pH than in neutral condition. Another feature of the conjugated micelles was a sustained release profile. The cytotoxicity of micelles were evaluated by MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, atetrazole) assay on lung cancer A549 cell lines. In vitro cytotoxicity assay showed that the mPEG–PCL copolymer did not affect the growth of A549 cells. The cytotoxic activity of the micelles against A549 cells was greater than free doxorubicin and free curcumin.     

超声造影评估早期骨再生血管化的实验研究

目的探讨超声造影(Contrast Enhanced Ultrasound,CEUS)在骨再生过程中骨移植材料早期血管化的应用价值,为临床骨再生不良提供早期诊断信息。方法将25只斯泼累格·多雷(Sprague Dawley,SD)级雄性大鼠,于左侧后肢近股骨头处肌间隙内植入磷酸钙骨水泥/重组人骨形态蛋白2(Calcium Phosphate Cement/recombination huaman Bone Morphogenetic Protein-2,CPC/rh BMP-2),建立大鼠肌内异位成骨模型。在术后3、7、14、21、28 d分别进行高频超声、CEUS及病理学检测。观察不同时间CPC/rh BMP-2内的血流灌注情况及骨生成情况,并与病理结果进行对照。结果 CEUS显示,术后3 d,支架外周见少许星点状造影剂灌注,随着时间的增加,造影剂逐步向中央填充,且时间-强度曲线定量分析显示,峰值强度(Peak Intensity,PI)及曲线下面积(Area Under the Curve,AUC)逐渐上升;术后14确d,PI和AUC均达到最大值,术后21、28 d造影剂的PI、AUC降低。各组间差异具有统计学意义(p0.05),各组间达峰时间(Tine To Oeak,TTP)差异无明显统计学意义(p0.05)。苏木精伊红(Hematoxylin-Eosin,HE)染色显示,术后3、7、14、21、28 d支架内可见不同程度的新生血管形成,术后14 d为显著,与CEUS检查相符。结论 CEUS可早期显示CPC/rh BMP-2的新生血管形成情况,为骨移植的生长评估及骨再生不良提供诊断依据。     

Resource settings have a major influence on the outcome of maintenance hemodialysis patients in South India

Chronic kidney disease is reaching epidemic proportions and the number of patients on renal replacement therapy (RRT) is increasing worldwide and also in developing countries. To meet the challenge of providing RRT, a few charity organizations provide hemodialysis units for underprivileged patients, as the private hospitals are unaffordable for the majority. There is a paucity of information on the outcome of dialysis in these patients. Here, we describe the outcome of hemodialysis patients comparing the middle‐ and upper‐class income group with the lower class income group. A retrospective analysis was carried out in 558 CKD patients initiated on maintenance hemodialysis in two different dialysis facilities. Group A (n=247) included those who belonged to the lowermost socioeconomic status and were undergoing dialysis in two nonprofit, charity (TANKER)‐run dialysis units, and Group B (n=311) was undergoing dialysis in a nonprofit hospital setting where no subsidy was given. Those patients of a low socioeconomic status, especially those who are diabetics, have a higher death rate (Group A‐38.1%, Group B‐4.2%) and loss to follow‐up (Group A‐25.9%, Group B‐0.3%) compared with those who are in the middle‐ and high‐income group. Higher EPO use and hence higher hemoglobin levels (Group A‐6.4±1.2, Group B‐8.9±1.5 P<0.001) were observed in those who were in the middle and the higher income group. Lower serum phosphorus level was observed in the low‐socioeconomic group (Group A‐4.7±1.5, Group B‐5.5±1.9, P<0.001). Patients belonging to the middle and higher socioeconomic group undergo more transplantations compared with the lower socioeconomic group (Group A‐2.4%, Group B‐65.6%).     

Influence of quercetin on the pharmacokinetics of ranolazine in rats and in vitro models

The aim of our study was to enhance the bioavailability of ranolazine by using herbal-bioenhancer quercetin in rats and to study the role of P-glycoprotein (P-gp) in vitro models. In single dose study (SDS), rats were divided into four groups, Group I was treated with 0.5% sodium carboxy methyl cellulose (SCMC), Group II was treated with ranolazine (14?mg/kg), Group III was treated with quercetin (20?mg/kg) and Group IV was treated with both ranolazine and quercetin. The blood samples were collected at 0.5, 1, 2, 3, 4, 6, 8 and 12?h, and the concentration of ranolazine in the plasma was estimated by reverse phase high performance liquid chromatography (RP-HPLC) method. In multiple dose study (MDS), rats were treated with same drugs for 7 days. On 8th day, the concentration of ranolazine in plasma was estimated. In vitro study performed on the rat and chick intestinal sacs to study the intestinal transport of ranolazine in the presence and absence of quercetin and verapamil (P-gp-inhibitor). Quercetin increased the peak concentration (C_max) of ranolazine from 254?±?8.45 to 324?±?10.21 and 331?±?9.65?ng/mL in SDS and MDS, respectively. Quercetin also increased area under the curve (AUC) of ranolazine from 1565.12?±?52.24 to 2016.98?±?142.65 and 2070.85?±?271.60?ng/mL/h in SDS and MDS, respectively. The transport of ranolazine from mucosal side to serosal side was increased in presence of quercetin. Quercetin is an inhibitor of CYP3A4 and P-gp. So it increased the AUC and C_max of ranolazine.     

The protective effects of apocynin on ionizing radiation-induced intestinal damage in rats

Background and aims: Radiation colitis typically emerges during radiotherapy of intra-abdominal malignancies. While the underlying mechanism remains unclear, it is considered that free oxygen radicals act like cellular mediators to cause colonic damage. Apocynin (APO) prevents oxidative stress and apoptotic cell death by inhibiting NADPH oxidase, and preventing the formation of free oxygen radicals. The aim of the present study was to investigate the protective effect of APO, a strong antioxidant and antiinflammatory agent, on radiation induced colonic oxidative damage in rats.

Materials and methods: Rats were randomly divided into four groups (n?=?8/group). Group I (control group); Group II (Group RAD) received a single dose of 800 cGy ionizing radiation to the whole abdomen with a linear accelerator (LINAC); Group III (Group APO) received a single dose of 20?mg/kg of APO intraperitoneally for five days; Group IV (Group APO+RAD) received APO for five days before radiation exposure (similar to Group III), (similar to Group II).

Results: APO treatment prior to radiation led to protection in the biochemical and histopathological parameters.

Conclusions: Our study shows that APO treatment before radiation improves radiation induced colonic injury in rats, by decreasing oxidative stress and apoptosis.     

Outcomes of Severe Methanol Intoxication Treated with Hemodialysis: Report of Seven Cases and Review of Literature

To identify factors associated with the outcome of severe methanol intoxication treated with hemodialysis, we analyzed the clinical course of 7 patients admitted with serum methanol level higher than 50 mg/dL, and therefore requiring hemodialysis. Four patients (group A) had adverse outcomes (1 death, 3 severe neurological deficits and/or blindness) and 3 patients (group B) had no adverse outcomes. Compared to group B, group A appeared to have a longer delay between ingestion of methanol and arrival at the emergency department (ED), a longer wait in the ED until ethanol infusion was started (3.6 ± 2.7 vs 1.3 ± 0.9 hr, p < 0.05), and, on admission, higher serum methanol (504 ± 219 vs 321 ± 228 mg/dL, p < 0.05), higher serum osmolality (460.5 ± 98.2 vs 397.6 ± 52.3 mOsm/kg, p < 0.05), higher serum osmolal gap (162.6 ± 76.7 vs 105.6 ± 52.9 mOsm/kg, p < 0.05), lower arterial pH (6.86 ± 0.08 vs 7.38 ± 0.16, p < 0.01), lower serum bicarbonate (4.6 ± 1.6 vs 19.9 ± 5.7 mmol/L, p < 0.01), and higher serum anion gap (36.5 ± 1.3 vs 14.3 ± 6.7 mEq/L, p < 0.01). Delay in the ED until hemodialysis was started did not differ (group A 6.4 ± 2.6 hr, group B 5.3 ± 3.5 hr), while duration of hemodialysis until serum methanol levels became permanently undetectable was longer in group A (15.0 ± 0.5 vs 8.4 ± 4.4 hr, p < 0.01). The ingested dose of methanol and the delay between ingestion and initiation of therapy to block methanol metabolism (ethanol infusion) and remove methanol from the body (hemodialysis) appear to be the critical factors influencing the outcome of methanol intoxication. Early diagnosis and initiation of treatment before substantial parts of the ingested methanol have been metabolized are of paramount importance in ensuring a favorable outcome.     

The effect of clopidogrel on pharmacokinetics of ivabradine and its metabolite in rats

The present study aimed to investigate the effect of clopidogrel (CLO) on pharmacokinetics of ivabradine (IVA) and its metabolite in rats and develop a reliable method to determine IVA and its metabolite N-demethyl ivabradine in serum. Healthy male SD rats were randomized to be given 0.8?mg/kg IVA or IVA combined with 8?mg/kg CLO. Blood samples were collected at 0.083, 0.16, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24?h after administration. The serum concentrations of IVA and N-demethyl ivabradine were determined by ultra-performance liquid chromatography–mass spectrometry and pharmacokinetic parameters were calculated using DASver3.0 software. The parameters of AUC_(0???t), AUC_(0???∞), and C_max for IVA in the group of IVA?+?CLO were significantly higher than those in the group of IVA (p?t_1/2) in the IVA?+?CLO group was extended compared to IVA (p?p?(0???_t), AUC_(0???∞), and C_max for N-demethyl ivabradine in the group of IVA?+?CLO was significantly compared to the group of IVA (p?p?t_1/2 was slightly increased. In this study, we find that CLO restrains the metabolism of IVA into N-demethyl ivabradine, which may be related to its competitive inhibition effect on cytochrome P450 isoform 3A4(CYP3A4).     

Assessment of effects of IR and IPC on activities of cytochrome P450 isozymes in rats by a five-drug cocktail approach

Background and objective: To evaluate the effects of ischemia and reperfusion (IR) and ischemic preconditioning (IPC) on the metabolic activities of cytochrome P450 (CYP) isozymes in rats by a five-drug cocktail approach.

Methods: Cocktail approach was used to evaluate the influence of IR and IPC on the activities of CYP1A2, CYP2C9, CYP2E1, CYP2D6 and CYP3A4, which were reflected by the changes of pharmacokinetic parameters of five specific probe drugs: caffeine, chlorzoxazone, tolbutamide, metoprolol and midazolam, respectively. Rats were randomly divided into IR, IPC and sham groups, and then injected the mixture of five probe drugs. Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by a HPLC method with UV detection. The pharmacokinetic parameters were calculated by the software of DAS 2.0.

Results: The parameters including t_1/2β, CLs, AUC, MRT and K₁₀ exhibited a similar tendency for both IR and IPC groups. Compared with sham group, CLs and K₁₀ of five probe drugs were significantly lower (p?t_1/2β of five or some probe drugs were significantly increased in IR and IPC groups (p?p?Conclusion: IR can variably decrease the activities of CYP isozymes in rats and this decrease can be attenuated by IPC.     

Pharmacokinetic interaction study of combining imatinib with dasatinib in rats by UPLC–MS/MS

Abstract

This study examined whether oral administration of dasatinib to the rats with imatinib led to any pharmacokinetic interactions. Twenty-four rats were divided randomly into three groups, imatinib group (imatinib 25?mg/kg, n?=?8), dasatinib group (dasatinib 15?mg/kg, n?=?8) and co-administration group (dasatinib 15?mg/kg and imatinib 25?mg/kg, n?=?8). The concentration of imatinib and dasatinib in rat plasma was determined by a sensitive and simple UPLC–MS/MS method. There was statistical pharmacokinetics difference for imatinib in the imatinib group and co-administration group, when co-oral administration imatinib with dasatinib, MRT_(0–t) increased (p?<?0.01). There was statistical pharmacokinetics difference for dasatinib in the dasatinib group and co-administration group, when co-oral administration dasatinib with imatinib, C_max and AUC increased (p?<?0.01), CL and V decreased (p?<?0.01). These data indicate dasatinib could slightly influence the pharmacokinetic profile of imatinib in rats, and imatinib could influence the pharmacokinetic profile of dasatinib in rats, which might cause drug–drug interactions when using imatinib with dasatinib.     

Arterial Hypertension Is Associated with Increased Serum Lipoprotein(a) Levels in End‐Stage Renal Disease Patients

In addition to disorders in lipoprotein metabolism, several other factors are involved in the development of atherosclerotic changes in end‐stage renal disease (ESRD) patients. One of these is arterial hypertension. We evaluated serum lipids—total cholesterol (TC), triglycerides (TG), apolipoproteins (A_I , A _II , B, E), lipoprotein(a) [Lp(a)]—in 109 ESRD patients on dialysis [46 on hemodialysis (HD); 63 on continuous ambulatory peritoneal dialysis (CAPD)] and in 45 hyperlipidemic patients without renal failure (HL group). Dialysis patients were divided in two groups. Group A included 42 hypertensive patients (mean age: 62.3 ± 15.5 years) whose blood pressure (BP) was satisfactorily controlled with anti‐hypertensive medications. Group B included 67 non hypertensive patients (mean age: 66.6 ± 11.9 years). Levels of Lp(a) were significantly higher in both the HD (p = 0.001) and the CAPD (p < 0.05) patients as compared with the HL group. When the HD and CAPD groups were divided into hypertensive and non hypertensive patients, Lp(a) levels were significantly higher in the hypertensive patients; this difference was not observed among non renal failure patients. These results indicate that arterial hypertension is associated with elevated Lp(a) serum levels in ESRD patients undergoing either HD or CAPD.     

Inhibitory effect of resveratrol on the pharmacokinetic of ibrutinib by UPLC–MS/MS

Objective: To investigate the impact of resveratrol on the metabolism of ibrutinib in vitro and in vivo.

Methods: In vitro, rat liver microsomes (RLM) and human liver microsomes (HLM) were used to study. In vivo, 18 male SD rats were randomly divided into three groups (n?=?6): ibrutinib and the multiple dose of 100?mg/kg resveratrol for consecutive 7 days (Group A), ibrutinib and the single dose of 100?mg/kg resveratrol (Group B), ibrutinib (Group C). Processed samples were analyzed by UPLC–MS/MS.

Results: Resveratrol showed inhibition on RLM and HLM in vitro. The IC₅₀ of resveratrol was 8.745?µM in RLM and 7.789?µM in HLM. Furthermore, Groups A and B both increased the AUC and reduced the CLz/F. The C_max of Group A and the MRT_(0–t) of Group B were significantly improved.

Conclusions: Resveratrol inhibits the pharmacokinetic of ibrutinib in vitro and in vivo. It is necessary to pay more attention to adjust the dose of the drug when resveratrol is used in combination with ibrutinib.     

Acutely repaired proximal anterior cruciate ligament ruptures in sheep – by augmentation improved stability and reduction of cartilage damage

The aim of this study was to evaluate the healing capacity of proximal anterior cruciate ligament (ACL) ruptures following primary repair with and without a bioresorbable augmentation. The ACL was transected at the femoral origin in the right knee joint of 24 sheep. The ACL was repaired in eight sheep (group B) without, and in eight sheep (group C) with a bioresorbable augmentation. Eight sheep without repair served as a control (group A). No immobilization was performed in any group. The sheep were sacrificed 13 weeks post-operatively. Macroscopically, all repaired ACLs were healed. The augmentation device was broken in all cases, but not completely degraded. In group A, none of the transected ACLs had healed. The anterior drawer under a load of 50 N was significantly lower in group C than in group A (p<0.01). No significant difference was seen between groups B and A. The distribution and extent of chondromalacia (CM) in the operated knees depended on the type of operative treatment (p<0.01). Groups A and B showed significantly more CM in the operated knee than in the non-operated knee (each p<0.05). Proximal ACL ruptures can heal in sheep after both non-augmented and augmented ACL repair with free-functional rehabilitation. However, augmented repair leads to significantly better stability of the knee joint compared to transected controls and better limits the development of degenerative changes.     

Modeling of particle size distribution and energy consumption of wet milled maize at varying soaking period and method in the production of Ogi

Energy consumptions and particles size distribution of soaked maize grains at varying time were studied and modeled. Rosin–Rammler–Bennet (RRB) model well fitted first milling size distribution with a high coefficient of determination (R²) and low root mean square error (RSME). The milling energy of maize grains decreased significantly (p?<?0.05) with increase in soaking time. The milling energy decrease from 32 to 8.72?kWh/kg and 32.00 to 9.00?kWh/kg for maize variety E9W at 24th hour soaking conditions of 28 and 65°C, respectively. Similar observations for A4W, B2Y and C3Y at 24?h of soaking were recorded. The Work index, Kick’s and Rittinger’s constants decreased with increase in soaking time. There was significant difference (p?<?0.05) in values obtained for Bond work index, Rittinger’s and Kick’s constants; these decreased with increase in soaking time. Predicted energy consumption followed similar trend. The interaction effect between energy consumption, Moisture content, and Milling time showed a high R² (0.8767–0.99349); while the regressed model for determining energy consumption from relationship between the mass, moisture content, milling time and the ratio of the geometric diameter mean and final size of the product were also established in this work with R² ranging from 0.9355 to 0.967.