Subchronic toxicity of Acorus gramineus rhizoma in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Acorus gramineus rhizoma (AGR) is the dry rhizome of Acorus gramineus Solander from the family Araceae that has been used as sedative, analgesic, diuretic, digestive and antifungal agent. AIM OF THE STUDY: To evaluate the no-observed-adverse-effect level (NOAEL) and the toxicity of AGR, following repeated oral administration to rats for 13 weeks. MATERIALS AND METHODS: AGR was administered by oral gavage to groups of rats (10 per group, each sex) at doses of 0 (control), 25, 74, 222, 667, or 2,000mg/kg/day, 5 times per week for 13 weeks. Mortality, clinical signs, body weights, food consumption, hematology, serum chemistry, urinalysis, vaginal cytology, sperm motility, sperm morphology, organ weights, gross and histopathological findings were compared between control and AGR groups. RESULTS: No mortality or remarkable clinical signs were observed during this 13-week study. No adverse effects on body weight, food consumption, urinalysis, hematology, serum chemistry, organ weights, gross lesion, histopathology, vaginal cytology, sperm motility or deformity were observed in any of the male or female rats treated with AGR. CONCLUSIONS: On the basis of these results, the NOAEL of AGR is determined to be 2,000mg/kg/day for male and female rats.

Acute and 28-Day Subacute Toxicity Studies of Hexane Extracts of the Roots of Lithospermum erythrorhizon in Sprague-Dawley Rats.

Lithospermum erythrorhizon has long been used as a traditional oriental medicine. In this study, the acute and 28-day subacute oral dose toxicity studies of hexane extracts of the roots of L. erythrorhizon (LEH) were performed in Sprague-Dawley rats. In the acute toxicity study, LEH was administered once orally to 5 male and 5 female rats at dose levels of 500, 1,000, and 2,000 mg/kg. Mortality, clinical signs, and body weight changes were monitored for 14 days. Salivation, soft stool, soiled perineal region, compound-colored stool, chromaturia and a decrease in body weight were observed in the extract-treated groups, and no deaths occurred during the study. Therefore, the approximate lethal dose (ALD) of LEH in male and female rats was higher than 2,000 mg/kg. In the subacute toxicity study, LEH was administered orally to male and female rats for 28 days at dose levels of 25, 100, and 400 mg/kg/day. There was no LEH-related toxic effect in the body weight, food consumption, ophthalmology, hematology, clinical chemistry and organ weights. Compound-colored (black) stool, chromaturia and increased protein, ketone bodies, bilirubin and occult blood in urine were observed in the male and female rats treated with the test substance. In addition, the necropsy revealed dark red discoloration of the kidneys, and the histopathological examination showed presence of red brown pigment or increased hyaline droplets in the renal tubules of the renal cortex. However, there were no test substance-related toxic effects in the hematology and clinical chemistry, and no morphological changes were observed in the histopathological examination of the kidneys. Therefore, it was determined that there was no significant toxicity because the changes observed were caused by the intrinsic color of the test substance. These results suggest that the no-observed-adverse-effect Level (NOAEL) of LEH is greater than 400 mg/kg/day in both sexes.

Subchronic toxicity study of Coptidis rhizoma in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Coptidis Rhizoma (CR) is a medical herb from the family Ranunculacease that has been used to treat gastroenteritis, dysentery, diabetes mellitus, and severe skin diseases. AIM OF THE STUDY: To evaluate the no-observed-adverse-effect level (NOAEL) and the toxicity of CR, following repeat oral administration to rats for 13 weeks. MATERIALS AND METHODS: CR was administered by oral gavage to groups of rats (n=10/group, each sex) at dose levels of 0 (control), 25, 74, 222, 667 or 2000 mg/kg/day 5 times per week for 13 weeks. Mortality, clinical signs, body weights, food consumption, hematology, serum chemistry, urinalysis, vaginal cytology and sperm morphology, organ weights, gross and histopathological findings were compared between control and CR groups. RESULTS: Urinalysis showed a significant increase in N-acety1-ß-glucosaminidase in males in the 2000 mg/kg/day group (P<0.01). However, no mortality or remarkable clinical signs were observed during this 13-week study. No adverse effects on body weight, food consumption, hematology, serum chemistry, organ weights, gross lesion, histopathology, vaginal cytology, sperm motility, or deformity were observed in the males or female rats treated with CR. CONCLUSIONS: On the basis of these results, the NOAEL of CR is determined to be 667 mg/kg/day for males and 2000 mg/kg/day for females.

Subchronic oral toxicity of evodia fruit powder in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Evodia, a fruit from Evodia rutaecarpa, has been used in oriental medicine, and since its various pharmaceutical actions, including anti-cancer activity, have become known, evodia has been widely used as a dietary supplement. However, information regarding its toxicity is limited. MATERIALS AND METHODS: Evodia fruit from Evodia rutaecarpa (Juss.) Benth. var. officinalis (Dode) Huang (0, 25, 74, 222, 667, and 2000 mg/kg) was administered orally five times per week for 13 weeks. Clinical signs, body weight, food consumption, hematology, serum chemistry, urinalysis, vaginal cytology, sperm morphology, organ weight, and gross and histopathological findings were evaluated. RESULTS: Urinary ketone body excretion was detected in males at 667 and 2000 mg/kg and in females at 2000 mg/kg. An increase in absolute/relative liver weight was observed in both sexes at 2000 mg/kg. Although levels of serum alanine aminotransferase, glucose, total cholesterol, and triglycerides were significantly reduced in males and/or females at 200 and/or 667 and 2000 mg/kg, all values were within normal ranges and were considered non-adverse. In addition, no treatment-related differences in body weight, food consumption, hematology, vaginal cytology, sperm morphology, or gross and histopathological examination were detected. CONCLUSIONS: The subchronic no-observable-adverse-effect level for evodia fruit powder following oral administration in rats is greater than 2000 mg/kg.

Comparison of dexmedetomidine and epinephrine as an adjuvant to 1% mepivacaine in brachial plexus block / 대한마취과학회지

BACKGROUND: Dexmedetomidine extends the duration of nerve block when administered perineurally together with local anesthetics by central and/or peripheral action. In this study, we compared the duration of nerve block between dexmedetomidine and epinephrine as an adjuvant to 1% mepivacaine in infraclavicular brachial plexus block. METHODS: Thirty patients, scheduled for upper limb surgery were assigned randomly to 3 groups of 10 patients each. We performed brachial plexus block using a nerve stimulator. In the control group (group C), patients received 40 ml of 1% mepivacaine. In group E, patients received 40 ml of 1% mepivacaine containing 200 microg of epinephrine as an adjuvant. In group D, patients received 40 ml of 1% mepivacaine containing 1 microg/kg of dexmedetomidine as an adjuvant. Sensory block duration, motor block duration, time to sense pain, and onset time were assessed. We also monitored blood pressure, heart rate, oxygen saturation and bispectral index. RESULTS: In group D and group E, sensory block duration, motor block duration and time to sense first pain were prolonged significantly compared to group C. However, there was no significant difference between group D and group E. CONCLUSIONS: Perineural 1 microg/kg of dexmedetomidine similarly prolonged nerve block duration compared to 200 microg of epinephrine, but slowed heart rate. Thus, dexmedetomidine is expected to be a good alternative as an adjuvant to local anesthesia in patients who are cautioned against epinephrine.

A four-week repeated study of intravenous toxicity of recombinant human interleukin-2 in Sprague-Dawley rats.

Interleukin-2 (IL-2) is a lymphokine with a potential role in cancer therapy. Many clinical trials of recombinant human IL-2 (rhIL-2) have been conducted to treat malignant renal carcinoma, melanoma, leukemia, lymphoma, multiple myeloma. BMI Korea has developed a method to manufacture rhIL-2 in bulk using Escherichia coli as a biosimilar. Prior to conducting human clinical trials, 4-week repeated toxicity study of rhIL-2 was conducted. In this study, rhIL-2 was administered intravenously to rats at doses of 9×10(6), 18×10(6), and 36×10(6)IU/kg/day over a period of 4 weeks. Adverse effects were observed in RBC, HGB, HCT, reticulocyte, mesenteric lymph node from middle dose, and changes of total bilirubin, femoral bone marrow, thymus, and clinical signs were observed at high dose. Local irritation was determined at low dose of female rats and at middle dose of male ones. Taken together, no observed adverse effect levels (NOAEL) was determined at dose of 9×10(6)IU/kg/day in male, and NOAEL was determined under the dose level in female rats. It suggests that present rhIL-2 is less toxic prior produced rhIL-2 and may be contribute more effective cancer-treatment strategy in human.

The Comparison of the Concentration of Free Hemoglobin in Packed RBC, Intraoperative Salvaged Blood and CPB Residual Blood during Cardiac Surgery / 대한마취과학회지

BACKGROUND: Intraoperative autotransfusion or residual blood in a cardiopulmonary bypass (CPB) circuit has been used to reduce the need for an homologous blood transfusion during cardiac surgery. However, it may contain some free hemoglobin released from damaged cells. The load of blood containing free hemoglobin may cause renal dysfunction. We measured the amount of free hemoglobin in banked blood, cell saver blood and CPB blood to evaluate what is the least hemolytic blood transfused in cardiac surgery. METHODS: This study was performed in 20 patients undergoing cardiac surgery. In each patient, the banked blood, intraoperative salvaged blood with a cell saver and CPB residual blood were sampled at the end of the operation. The concentration of free hemoglobin, hemoglobin and platelet counts were measured in these blood samples and percent of hemolysis was calculated (%hemolysis = [free hemoglobin] / [free hemoglobin hemoglobin]) RESULTS: In salvaged blood with a cell saver, CPB residual blood and banked blood, hemoglobin concentrations were 20.1+/-2.7 g/dl, 8.0+/-1.1 g/dl, and 22.2+/-2.7 g/dl, respectively. Free hemoglobin concentrations were 336.6+/-239.5 mg/dl, 49.2+/-26.8 mg/dl, and 279.5+/-167.5 mg/dl respectively. Platelet counts were 26.1+/-22.2X10(3)/mm3, 116.8+/-56.5X10(3)/mm3, and 94.9+/-43.6X10(3)/mm3 respectively. % Hemolysis were 1.6+/-1.1%, 0.6+/-0.4%, and 1.2+/-0.7% respectively. In the comparison between the salvaged blood with a cell saver and CPB residual blood, free hemoglobin concentration, % hemolysis, and platelet counts had positive correlations (r = 0.8, 0.7, and 0.6). CONCLUSIONS: In twenty cardiac surgeries, CPB residual blood had a lower free hemoglobin level than the other two blood groups. The platelet counts in CPB residual blood were higher than those in cell saver blood but did not differ from those in banked blood. Therefore, CPB residual blood was the least hemolytic blood among the three blood groups when a transfusion was performed in cardiac surgery.

The Effects of Pre-incisional Lidocaine Infiltration into Tonsils with Low-dose Fentanyl Supplementation on the Blood pressure and the Heart rate for Pediatric Adenotonsillectomy / 대한마취과학회지

The purpose of this study was to evaluate the effects of pre-incisional lidocaine injected into tonsils with low-dose fentanyl supplementation on the cardiovascular stability and on the developrnent of intraoperative arrhythmia for pediatric adenotonsillectomy under general anesthesia. Thirty-three pediatric patients undergoing adenotonsillectomy under general anesthesia were randomly aUocated to one of the 3 groups according to the medications used for anesthesia.; 1) N2-O2-halothane only, 2) N2-O2-halothane plus pre-incisional infiltration of 2% lidocaine and 1: 80,000 epinephrine into tonsils after tracheal intubation, 3) N2-O2-halothane plus 2 mcg/kg intravenous fentanyl before induction of anesthesia plus pre-incisional infiltration of 2% lidocaine and 1: 80,000 epinephrine into tonsils after tracheal intubation. All Patients received (0.01/kg+0.15) mg atropine sulfate and 5 mg/kg thipental sodium and inhaled N2-O2-halothane (2 L-2 L-2 vol%) for induction. Tracheal intubation was facilitated with 1.5 mg/kg succinylcholine. After tracheal intubation, anesthesia was maintained with 5% N2O in oxygen and 1 vo1% halothane. 0.1 mg/kg vecuronium was used for myorelaxation. SBP, DBP, MAP, and HR were measured at 1 min, 3 min after intubation, immediately after the incision of tonsils, and after the position change of endotracheal tube. ECG changes were also observed during surgery. After surgery, the degree of irritability and the recovery time were evaluated in all patients in the recovery room. The results were as follows; 1) In Gmup 3, the increases of systolic BP at 3 min and HR at 1 min after tracheal intubation were significantly lower than other two groups. 2) The maximum value of intraoperative systolic BP was the highest in Group 1, followed by Group 2, and then Group 3. 3) The peak intraoperative HR attained was the lowest in Group 3. Difference between Group 1 and 2 was not significant. 4) No cardiac arrhythmia was present in Group 3, 5) The degree of postaperative imtabiTity was the lowest in Gmup 3 and the highest in Group 1. In conclusion, these results indicate that supplementation of low-dose fentanyl and preincisional infiltration of tonsils with lidocaine for pediatric adenotosillectomy under genral anesthesia is useful in reducing cardiovascular instability during tracheal intubation and surgery as well as the incidence of intraoperative cardiac arrhythmia, and postoperative pain.