Effect Of Administration Time Research Articles

Effect of meloxicam or robenacoxib administration timing on renal function and postoperative analgesia in cats undergoing ovariohysterectomy: A randomized, blinded, controlled clinicaltrial.

We evaluated the effect of administration timing of meloxicam and robenacoxib on renal function, platelet cyclo-oxygenase and perioperative analgesia in 60 cats undergoing ovariohysterectomy, in a prospective randomized blinded controlled study. Twelve cats were randomly allocated to one subcutaneous treatment group: meloxicam (0.2 mg/kg) or robenacoxib (2 mg/kg) at admission (MA, RA), at induction (MI, RI) and robenacoxib at the end of surgery (RE). All cats received the same anaesthesia protocol. Plasma renin activity (PRA), plasma creatinine, drug concentrations and serum thromboxane (TxB2) were measured sequentially. Anaesthesia significantly increased PRA, as activity at end of the surgery was higher than 2 h later (mean ± SD: 26.6 ± 2.8 versus 10.0 ± 3.9 ng/mL/h). PRA remained higher at 2 h post-surgery in admission groups compared to induction groups (p = .01). Serum TxB2 was lower with meloxicam than robenacoxib (p = .001), and was lower in the MA than each robenacoxib group at catheter placement. Admission groups (16/24 from RA and MA groups) received earlier rescue analgesia than other groups (p = .033). In conclusion, the renin-angiotensin system was activated during anaesthesia despite cyclo-oxygenase inhibition, possibly due to hypotension or surgical stimulation. There was no effect of drug or timing on the markers of renal function but one cat receiving meloxicam at induction had suspected IRIS grade II acute kidney injury.

Comparison of the Effect of Administration Time of Prophylactic Antibiotics on Post-Operative Wound Infection after Caesarean Section

Objective: To compare the post-operative wound infection rate after cesarean section in women receiving prophylactic antibiotics before skin incision with women receiving antibiotic after cord clamping of baby.
 Study design: Randomized controlled trial
 Place and Duration of Study: Department of Obstetrics and Gynecology, Holy Family hospital, Rawalpindi from October 2017 to April 2018.
 Materials & Methods: 356 patients pregnant female of age 20-45 years who were at term undergoing elective cesarean section for any indication were enrolled. All the patients were randomly divided into two groups. Group A (study group) was comprised of patients who received prophylactic antibiotic dose 15-60 min before the start of surgery. Group B (control group) was comprised of patients who received the antibiotic after the cord clamping of the baby. The wound infection was noted for both the groups. All the patients were followed up for 8 days to assess infection. Data was analyzed using SPSS version 22. 
 Results: Mean maternal age of the total study population found to be 28.6±5.3 years. Mean gestational age in all the enrolled patients found to be 37.7±1.2 weeks. Wound infection was noted in 28.4% (n=101) of total study population. Out of 101 total patients who presented with wound infection, 63 patients (62.4%) were of control group while only 38 (37.6%) patients belonged to study group. The difference was statistically significant (P<0.05).
 Conclusions: Prophylactic antibiotic are useful for controlling post cesarean wound infection.
 KEY WORDS: Cesarean delivery, Ceftriaxone, Wound infection

Determining the Optimal Administration Conditions under Which MIF Exerts Neuroprotective Effects by Inducing BDNF Expression and Inhibiting Apoptosis in an In Vitro Stroke Model.

Macrophage migration inhibitory factor (MIF) exerts neuroprotective effects against cerebral ischemia/reperfusion injury by inhibiting neuronal apoptosis and inducing the expression of brain-derived neurotrophic factor (BDNF). However, the optimal administration conditions of MIF are currently unknown. Here, we aimed to identify these conditions in an in vitro model. To determine the optimal concentration of MIF, human neuroblastoma cells were assigned to one of seven groups: control, oxygen and glucose deprivation/reperfusion (OGD/R), and OGD/R with different concentrations (1, 10, 30, 60, and 100 ng/mL) of MIF. Six groups were studied to investigate the optimal administration time: control, OGD/R, and OGD/R with MIF administered at different times (pre-OGD, OGD-treat, post-OGD, and whole-processing). Water-soluble tetrazolium salt-1 assay, Western blot analysis, and immunocytochemistry were used to analyze cell viability and protein expression. We found that 60 ng/mL was the optimal concentration of MIF. However, the effects of administration time were not significant; MIF elicited similar neuroprotective effects regardless of administration time. These findings correlated with the expression of BDNF and apoptosis-related proteins. This study provides detailed information on MIF administration, which offers a foundation for future in vivo studies and translation into novel therapeutic strategies for ischemic stroke.

Memantine effects on ingestion microstructure and the effect of administration time: A within-subject study.

In a between-subject comparison of two memantine administration schedules we observed that treatment with the NMDA receptor antagonist memantine before testing sessions reduced ingestion of a 10% sucrose solution in rats, due to reduced licking burst size, thus suggesting a blunted hedonic response. Conversely, daily post-session administration reduced burst number, indicating a reduced level of behavioural activation, likely due to the development of conditioned taste aversion (CTA). In this study, the effect of pre-session and post-session memantine administration was investigated within-subjects. Memantine was administered in daily intraperitoneal injections for 13 days, on alternate days, either 1-h before-"before testing" sessions-or immediately after a 30-min session-"after testing" sessions. The effects on the microstructure of licking for a 10% sucrose solution were examined in the course of treatment and for 21 days after treatment discontinuation. The results show reduced burst size in the "before testing" sessions, without effects on the intra-burst lick rate, an index of motoric effects. Moreover, burst number was reduced since the third session of both administration conditions until the end of treatment. Interestingly, the effect of memantine of reducing the activation of ingestive behaviour was less pronounced in this study with respect to that observed with the previous study post-session administration schedule, in spite of the longer treatment. This apparent paradox might be explained if one considers these effects as instances of a memory-related effect, such as the development of CTA. In the framework of this hypothesis, the "before testing" sessions, not being followed by memantine administration, can be considered as extinction sessions performed every other day. Moreover, the animals treated with memantine at the highest dose failed to recover to pre-treatment ingestion levels 21 days after treatment discontinuation, while the animals treated after testing sessions in the previously published study showed a complete recovery well before the 15th day test. Within the same interpretative framework, this might depend by the reduced number and frequency of the extinction trials-i.e. the number of the sessions run after treatment discontinuation-in the present study. These results provide further support to the conclusion that memantine administration before sessions reduce burst size, an effect which is likely due to blockade of NMDA receptors occurring during behavioural testing. The observation that this effect can be obtained even in absence of a reduced intra-burst lick rate, which rules out the involvement of motor impairment, provides an important piece of evidence in support to the interpretation of this effect as a blunted hedonic response. Moreover, these results provide further evidence that burst number reduction is due to a memory-related effect induced by memantine administration after sessions.

The Effect of Warfarin Administration Time on Anticoagulation Stability (INRange): A Pragmatic Randomized Controlled Trial.

Without supporting evidence, clinicians commonly recommend that warfarin be taken in the evening. We conducted a randomized controlled trial to evaluate the effect of administration time (morning vs evening) on the stability of warfarin's anticoagulant effect. A total of 236 primary care physicians serving 54 western Canadian communities mailed letters of invitation to all their warfarin-using patients. Eligible patients were community-dwelling warfarin users (any indication) with at least 3 months of evening warfarin use and no plans for discontinuation. Participants were randomized (by web-based allocation) to morning vs continued evening warfarin ingestion. We used the Rosendaal method to determine the proportion of time within therapeutic range (TTR) of the international normalized ratio (INR) blood test month 2 to 7 postrandomization vs the 6 months prerandomization. The primary outcome was the percent change in proportion of time outside target INR range (with an a priori minimum clinically important difference of ±20%). All analyses were intention to treat. Between March 8, 2015 and September 30, 2016, we randomized 109 participants to morning and 108 to evening warfarin use. TTR rose from 71.8% to 74.7% in the morning group, and from 72.6% to 75.6% in the evening group, for a change in TTR of 2.9% in the former vs 3.0% in the latter (difference, -0.1%; P = .97; 95% CI for the difference, -6.1% to 5.9%). The difference in percent change in proportion of time outside the therapeutic INR range (obtained via Hodges-Lehmann estimation of the difference in medians) was 4.4% (P = .62; 95% CI for the difference, -17.6% to 27.3%). Administration time has no statistically significant nor clinically important impact on the stability of warfarin's anticoagulant effect. Patients should take warfarin whenever regular compliance would be easiest.

The cacao procyanidin extract-caused anti-hyperglycemic effect was changed by the administration timings.

Mammals have the biological clocks with approximately 24 h-rhythm. Energy metabolism including glucose metabolism is regulated by the biological clocks. Glucose metabolism is affected by not only meal volume and its energy but also meal timing. We have reported that cacao liquor procyanidin-rich extract (CLPr) ameliorated the postprandial hyperglycemia through AMP-activated protein kinase pathway. However, the effect of administration timing of CLPr on the postprandial hyperglycemia and its signaling pathway are still unclear. In the present study, we compared the effect of CLPr-administration at the rest-phase (light-period) and active-phase (dark-period) on glucose metabolism. Single oral administration of CLPr to ICR mice at the rest-phase, but not at the active-phase, promoted phosphorylation of AMP-activated protein kinase and its upstream liver kinase B1 and translocation of glucose transporter 4 to the plasma membrane in the skeletal muscle, resulting in reduced postprandial hyperglycemia. These results indicated that the intake of CLPr at the rest-phase more effectively suppressed postprandial hyperglycemia.

The modified Si-Jun-Zi Decoction attenuates colon cancer liver metastasis by increasing macrophage cells

BackgroundThe modified Si-Jun-Zi Decoction (SJZ), a Chinese medicine formula, is clinically used against multiple malignancies including colorectal cancer (CRC). This study aims to evaluate the effect of modified SJZ on CRC liver metastasis and identify the therapeutic mechanisms.MethodsHuman CRC cells with GFP fluorescence were transplanted into Balb/c nude mice spleens. Modified SJZ, 5-fluorouracil or the combined treatment was given for 3 weeks. CRC liver metastasis was measured by fluorescence imaging and plasma cytokines were analyzed. Furthermore, the effects of administration time and doses for the modified SJZ were investigated in nude mice.ResultsModified SJZ could increase the survival rate and reduce CRC liver metastasis in the nude mice model. Plasma GM-CSF level was elevated. Three weeks of treatment with the modified SJZ at the full dose (45 g/kg) could significantly increase the number of macrophages but not neutrophils in the spleen.ConclusionsThese results indicate that modified SJZ can inhibit CRC liver metastasis by activating the innate immune system, providing a complementary and alternative therapy for CRC.

Effects of granulocyte colony-stimulating factor administration time on pain.

This study was aimed at evaluating the effect of administration time of granulocyte colony-stimulating factor (G-CSF) on the level of pain related to G-CSF. This study was carried out with 48 cancer patients divided into A and B groups. In the first stage of the study, the groups A and B were planned to be administered with G-CSF at 10: 00 and 14: 00, respectively. In the second stage, patients in groups A and B were asked to self-administer filgrastim at 14: 00 and 10: 00, respectively. Patients were also asked to assess their pain level after G-CSF administration for a total of 4 times. According to the findings, the incidence of pain related to G-CSF was 91.7 %. The pain score after G-CSF being administered at 10: 00 was significantly higher compared to administration at 14: 00 in both groups (group A after 4, 8, and 12 hours: p < 0.05; group B after 4 and 8 hours: p < 0.05). The results of the present study have demonstrated that the pain score related to G-CSF administration at 14:00 p.m. was significantly reduced. Thus, in order to minimize the pain, it will be more beneficial to administer G-CSF at 14: 00 (Tab. 4, Ref. 31). Text in PDF www.elis.sk.

Effect of administration timing of postchemotherapy granulocyte colony-stimulating factor on host-immune cell recovery and CD8+ T-cell response

Granulocyte colony-stimulating factor (G-CSF), a hematopoietic growth factor, is a standard supportive therapy given during cancer treatment. It induces acceleration in neutrophil recovery through stimulation of mobilization of hematopoietic progenitors. Given that the latter is also induced by chemotherapy itself, the timing of administration of G-CSF postchemotherapy might impact the resultant overall effects. The present study aimed to determine the optimal timing of G-CSF postchemotherapy to exert its optimal effects on the immune cell recovery and its impact on antigen-specific CD8+ T-cell response. B6 mice were treated once with cyclophosphamide (4 mg/mouse; CTX) and then daily with G-CSF (5 g/mouse) from Days 1–5, 2–5 or 5–9 post-CTX treatment. The total numbers of various immune cell types were analyzed on Days 7, 9 and 12 post-CTX treatment. To evaluate effects on CD8+ T-cell response, a pmel-1 transgenic mouse model was used in combination with prime boost peptide vaccination therapy. The total number of white blood cells (WBC), neutrophils, monocytes, lymphocytes, granulocytes and dendritic cells (DC) were significantly increased after G-CSF treatment in particular when G-CSF was administered from Days 2–5 post-CTX treatment. Application of this timing of G-CSF and CTX treatment after adoptive transfer of T-cells followed by prime-boost vaccination with antigenic peptide did not block the expansion of the donor pmel-1 CD8+ T-cells. In conclusion, adjusting the timing of treatment with G-CSF postchemotherapy can optimize its promoting effects on recovery of myeloid cells without altering the associated antigen-specific immunity.

Antibiotic prophylaxis for caesarean section at a Ugandan hospital: a randomised clinical trial evaluating the effect of administration time on the incidence of postoperative infections.

BackgroundProphylactic antibiotics are used to prevent postoperative infections after caesarean section. Studies have suggested that the timing of prophylaxis plays an important role. Over the years, the role of the anaesthesiologist in the administration of prophylactic antibiotics has become prominent. Therefore, there is an increasing need for anaesthesia providers to understand the rationale of antibiotic prophylaxis. We therefore sought to compare the effect of antibiotics prophylaxis within 1 hour before skin incision and after skin incision on the incidence of postoperative infections in patients undergoing caesarean section at Mulago Hospital.MethodsWe conducted a single-blind randomised clinical trial conducted at Mulago Hospital evaluating 464 patients undergoing emergency caesarean section. Patients were randomly assigned a group number that allocated them to either arm of the study. They received the same prophylactic antibiotic according to their allotment, that is, either within 1 hour before skin incision or after skin incision as per current standards of practice in Mulago Hospital. They were followed up to detect infection up to 10 days postoperatively. The primary outcome was postoperative infection. The data collected were analysed with STATA version 12 using univariate and bivariate analysis.ResultsThe risk of overall postoperative infection was significantly lower when prophylaxis was given within an hour before incision (RR O.77, 95% CI 0.62–0.97). We also found endometritis to be significantly reduced in the pre-incision group (RR 0.62; 95% CI 0.39–0.99; P value 0.036).ConclusionsGiving prophylactic antibiotics before skin incision reduces risk of postoperative infection, in particular of endometritis.Trial registrationPan African Clinical Trial Registry PACTR201311000610495.Date of trial registration: 12th August 2013.

Allogeneic adipose stem cell therapy in acute myocardial infarction

Stem cell therapy offers a promising approach to reduce the long-term mortality rate associated with heart failure after acute myocardial infarction (AMI). To date, in vivo translational studies have not yet fully studied the immune response to allogeneic adipose tissue-derived mesenchymal stem cells (ATMSCs). We analysed the immune response and the histological and functional effects of allogeneic ATMSCs in a porcine model of reperfused AMI and determine the effect of administration timing. Pigs that survived AMI (24/26) received intracoronary administration of culture medium after reperfusion (n = 6), ATMSCs after reperfusion (n = 6), culture medium 7 days after AMI (n = 6) or ATMSCs 7 days after AMI (n = 6). At 3-week follow-up, cardiac function, alloantibodies and histological analysis were evaluated. Administration of ATMSCs after reperfusion and 7 days after AMI resulted in similar rates of cell engraftment; some of those cells expressed endothelial, smooth muscle and cardiomyogenic cell lineage markers. Delivery of ATMSCs after reperfusion compared with that performed at 7 days was more effective in increasing: vascular density (249 ± 64 vs. 161 ± 37 vessels/mm2; P < 0.01), T lymphocytes (1 ± 0.4 vs. 0.4 ± 0.3% of area CD3(+) ; P < 0.05) and expression of vascular endothelial growth factor (VEGF; 32 ± 7% vs. 20 ± 4% of area VEGF(+) ; P < 0.01). Allogeneic ATMSC-based therapy did not change ejection fraction but generated alloantibodies. The present study is the first to demonstrate that allogeneic ATMSCs elicit an immune response and, when administered immediately after reperfusion, are more effective in increasing VEGF expression and neovascularization.

Effect of Administration Time of Exenatide on Satiety Responses, Blood Glucose, and Adverse Events in Healthy Volunteers

The objective was to investigate whether varying administration time of exenatide affects the magnitude of satiety responses, blood glucose, and adverse events in healthy volunteers. In this randomized, single-blind, placebo-controlled, 4-period crossover, single-dose study, the authors measured satiety responses, blood glucose, and adverse events in 20 participants receiving exenatide (10 µg) at either -60 minutes, -30 minutes, or -15 minutes or placebo at -30 minutes relative to a standardized test meal. Compared with placebo, exenatide reduced caloric intake (P = .0059), food intake (P = .0032), and glucose concentrations at 60 (P < .001) and 120 minutes after meals (P = .015). Nausea (63% vs 20%), reduced appetite (43% vs 10%), and vomiting (18% vs 0%) occurred more frequently in exenatide-treated subjects compared with placebo (P < .05). Significant differences were noted in caloric intake (P = .0149) and food intake (P = .0205) based on the administration time of exenatide, with doses given further from meals producing reduced feeding responses. No such difference was found in postprandial glucose concentrations or adverse events based on timing of exenatide administration. Single-dose exenatide administered further from mealtime had an increased magnitude on satiety responses in healthy volunteers. Postprandial glucose concentrations and the frequency of adverse events did not differ by the administration time of exenatide.

Administration of the Rho-Kinase Inhibitor Fasudil Before Ischemia or just After Reperfusion, but not 30 min After Reperfusion, Protects the Stunned Myocardium in Swine

We assessed the effect of administration time for fasudil treatment of the stunned myocardium in 40 anesthetized open chest swine. All swine were subjected to 12 min ischemia followed by reperfusion to generate stunned myocardium. Group A (n = 11) received saline in place of fasudil both before ischemia and after reperfusion. Group B (n = 10) received 30 min intravenous fasudil at a rate of 13 mug/kg/min starting 45 min before ischemia and received saline after reperfusion. Groups C (n = 10) and D (n = 9) received saline before ischemia, and received fasudil at a rate of 13 microg kg(-1) min(-1) starting just before reperfusion in group C and 30 min after reperfusion in group D. In both groups, treatment lasted 30 min. Myocardial contractility was assessed by percent segment shortening (%SS). Three swine in group A, 2 swine in each of groups B and C, and one swine in group D had ventricular fibrillation or tachycardia after reperfusion and were excluded from further analysis. The changes of %SS from baseline at 90 min after reperfusion in groups B and C were 68 +/- 8% and 75 +/- 8%, respectively, which were significantly higher than in group A or D (47 +/- 10% or 43 +/- 8%). We conclude that fasudil administered before ischemia or just after reperfusion, but not 30 min after reperfusion, protects the stunned myocardium.

Comparison of breakfast and bedtime administration of insulin glargine in children and adolescents with Type 1 diabetes

Objective The purpose of this study was to evaluate the effect of administration time of insulin glargine (IG) on glycemic control in children and adolescents with Type 1 diabetes. Materials and methods A total of 31 children and adolescents (15 F and 16 M) with Type 1 diabetes on intensive therapy (bedtime NPH and premeal insulin aspart) were randomized to receive once-daily IG either at breakfast (breakfast group, n = 15) or bedtime (bedtime group, n = 16) while continuing insulin aspart premeals for 6 months. Blood glucose levels were measured fasting, preprandially and bedtime. Total daily insulin dose (TDD), body mass index (BMI), glycosylated hemoglobin (HbA 1c), and frequency of hypoglycemia in the preceding 3 months were assessed at recruitment, third month and sixth month. Results The dose of IG, TDD, and fasting blood glucose levels were similar in both groups during the study period. The only significant difference in blood glucose levels between breakfast and bedtime groups was found for dinnertime at 6 months (135 ± 26 mg/dl versus 161 ± 33 mg/dl, respectively, p = 0.035). In the breakfast group, the mean HbA 1c level was significantly lower than that of baseline at month 6 (9.4 ± 2.5% versus 8.0 ± 0.9%, respectively, p = 0.022), whereas there was no significant change in the bedtime group (9.2 ± 2.1% versus 8.9 ± 2.2%, respectively). The frequency of hypoglycemia was lower with IG than NPH (2.7 ± 2.8/6 months versus 6.4 ± 6.7/6 months, respectively, p = 0.008). Conclusions Once-daily IG at breakfast in children and adolescents with Type 1 diabetes on intensive therapy is more efficacious than bedtime administration to improve metabolic control. Also, the number of hypoglycaemic events decreased with both breakfast and bedtime administrations of IG.

Endometrial thickness of postmenopausal breast cancer patients treatedwith tamoxifen

The effect of administration time of tamoxifen was assessed in 52 postmenopausal patients with mammary cancer in order to evaluate its effect on endometrium and serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol. Mean age of the patients was 61.5 years, 23% had a history of smoking, mean body mass index (BMI) was 26.9 kg/m2, and mean age at menarche, menopause and administration time of tamoxifen was 12.9, 48 and 3.5 years, respectively. Serum FSH and LH concentrations were decreased by 41.8% and 44.9%, respectively, compared with mean normal postmenopausal levels. The FSH decrement was associated with BMI and LH level, whereas the LH decrement was associated with patient age and FSH concentration. Endometrium thickness <5 mm was reported in 60.5% of the patients, while endometrium thickness ≥5 mm was found in 39.5% of the cases. Histology revealed that 75% of the patients had atrophic endometrium; the remaining patients (25%) did not show atrophic changes. Administration time of tamoxifen was not associated with endometrial thickness or with serum FSH and LH concentrations.

Pharmacologic approaches to daytime and nighttime symptoms of allergic rhinitis

Allergic rhinitis is associated with sleep disturbances, daytime somnolence, and fatigue. The exact relationship between rhinitis and sleep disturbance is unknown; however, both the symptoms and underlying pathology of allergic rhinitis can interfere with sleep quality. Nasal congestion, which has been shown to cause sleep-disordered breathing, is thought to be primarily responsible for rhinitis-related sleep disorders. The severity of nasal congestion follows a circadian rhythm, being worst at night and in the early morning. Chronotherapy is the study of the effects of administration time on the safety and efficacy of drug therapy based on circadian influences on the pharmacokinetics and pharmacodynamics of medications. Chronotherapy studies in allergic rhinitis suggest there are benefits to nighttime dosing of antiallergy medications. For example, the antihistamine mequitazine has shown improved efficacy when administered in the evening compared with morning dosing. More study is needed to determine whether this is a class effect. Leukotriene receptor antagonists are indicated for evening administration; these drugs significantly improve nighttime rhinitis symptoms. Intranasal corticosteroids administered in the morning have demonstrated efficacy in improving nighttime symptoms; however, it is unknown whether evening administration would improve their effects on nocturnal rhinitis symptoms. Because of the significant detrimental effects of nocturnal rhinitis symptoms on quality of life, allergic rhinitis therapies should be evaluated for efficacy in ameliorating nighttime symptoms.

Enhancement of Radiation- induced Mortality by Friend Leukemia Virus Infection: Differential Effects of Administration Timing on Hematopoiesis

Enhancement of Radiation- induced Mortality by Friend Leukemia Virus Infection: Differential Effects of Administration Timing on Hematopoiesis

Effects of carbon tetrachloride administration on initiation of liver cell foci by the non-hepatocarcinogens N-methyl- N′-nitro- N-nitrosoguanidine (MNNG) and benzo( a)pyrene (B(a)P)

In a development trial for an initiation bioassay system, cell proliferation kinetics after partial hepatectomy (PH) or CCl 4 administration (1 ml/kg b.w., i.g.) and the effect of administration time after PH or CCl 4 treatment on liver cell foci induction by the direct and indirect non-hepatocarcinogens, N-methyl- N′-nitro- N-nitrosoguanidine (MNNG) and benzo( a)pyrene (B(a)P) were investigated. Male F344 rats were killed 12, 18, 24, 36, 48, 72 or 96 h after PH or CCl 4 treatment and liver cell proliferation was examined with the bromodeoxiuridine (BrdU) labeling method. Appreciable increase in the BrdU labeling index was observed 18–36 h after PH with a peak at 24 h, and 18–72 h following treatment with CCl 4 with a peak at 48 h. MNNG (80 mg/kg i.g.)or B(a)P (100 mg/kg i.g.) were administered to 7-week-old male F344 rats at various times after PH or CCl 4 treatment and lesion induction was assessed using the resistant hepatocyte model. MNNG caused significant numbers of glutathione S-transferase placental form (GST-P)-positive liver cell foci in rats when given 12–36 h after PH, with a peak at 24 h. In contrast, the numbers of foci induced by B(a)P were maximal with exposure at 12 h after PH. In the CCl 4 study, both MNNG and B(a)P induced significant increase in GST-P-positive liver cell foci when given 12–72 h after CCl 4 treatment, with a peak at 48 h, the results being directly in line with the changes in BrdU labeling. From these findings, it is concluded that initiation assay protocols with a CCl 4 proliferative stimulus to hepatocytes may prolong the appropriate administration period for effective detection of the initiation potential of both direct and indirect carcinogens targeting sites other than the liver.

Effect of Administration Time of Lidocaine on the Cardiovascular Changes induced by Endotracheal Intubation

Effect of Administration Time of Lidocaine on the Cardiovascular Changes induced by Endotracheal Intubation

Ａｍｉｋａｃｉｎの薬物動態に及ぼす投与タイミングの影響

Ａｍｉｋａｃｉｎの薬物動態に及ぼす投与タイミングの影響