Effects of Nitrous Oxide and Remifentanil on Cardiovascular Response to Endotracheal Intubation during Desflurane Anesthesia

BACKGROUND: Desflurane is known to causes hypertension and tachycardia when its inspired concentration is rapidly increased. We determined whether nitrous oxide (N2O) or remifentanil alters cardiovascular responses to intubation and/or inhalation of high concentrations of desflurane during induction of anesthesia. METHODS: Sixty patients were assigned randomly into three groups (n = 20 each). Anesthesia was induced with thiopental 5 mg/kg followed by saline (control and N2O groups) or remifentanil 1microg/kg (remifentanil group). Tracheal intubation was facilitated with intravenous vecuronium 0.12 mg/kg and 12% desflurane was given soon after the intubation. In addition, 75% N2O was given beginning 3 min before the intubation in the N2O group. Systolic arterial pressure (SAP), heart rate (HR), and plasma catecholamine concentrations were determined. RESULTS: The intubation resulted in an immediate increase and an additional second increase of SAP and HR at 3 to 5 min after intubation in all groups. SAP but not HR in the N2O group and both SAP and HR in the remifentanil group at first and second peak responses were lower than in the control group. Norepinephrine increased at 1 min after intubation and increased further at 5 min in the control and N2O groups but only increased at 5 min in the remifentanil group. CONCLUSIONS: A biphasic pressor and tachycardiac response in response to intubation and desflurane were noted. Although N2O did not affect tachycardiac response, it suppressed the pressor responses and augmented norepinephrine release. However, remifentanil significantly attenuated hemodynamic and catecholamine responses to endotracheal intubation and desflurane.

The effect of remifentanil and lidocaine on time interval acquired for successful tracheal intubation in inhalational induction using sevoflurane / 대한마취과학회지

BACKGROUND: This study was conducted to investigate the optimal time interval for tracheal intubation and the effect of adjuvant drugs such as remifentanil and lidocaine during induction and tracheal intubation using sevoflurane inhalation without muscle relaxant. METHODS: This study enrolled patients with the age of 20-60 years old and ASA 1 or 2. Patients were randomly assigned into one of 4 groups (S, SR, SRL, SL), in which they were given remifentanil (R) i.v. at a rate of 0.25microgram/kg/min, or lidocaine (L) i.v. bolus of 1.5 mg/kg during sevoflurane inhalation (S). Anesthesia was performed as inhalation induction 2 minutes after pre-filling with sevoflurane 8 vol%. The time interval between induction and tracheal intubation was determined using up-and-down method. When satisfied all of the categories of response to tracheal intubation, the case was assigned to 'success', otherwise 'fail'. In each groups, effective time for successful intubation in 50% (ET50) and 95% (ET95) were calculated by probit analysis. RESULTS: ET50 was 3.90 minutes (95% confidence interval 3.32-4.38) in group S, 3.18 minutes (2.92-3.48) in group SL, 2.83 minutes (2.47-3.07) in group SR, and 2.68 minutes (2.37-2.95) in group SRL. In group S, SL, SR, and SRL, ET95 was 4.52 minutes (4.17-7.95), 3.63 minutes (3.37-4.97), 3.30 minutes (3.06-4.64), and 3.12 minutes (2.89-4.42), respectively. CONCLUSIONS: The optimal time to intubate successfully using sevoflurane without muscle relaxant in 95% patients was 4.5 minutes. The optimal time is reduced to 3.1 minutes by coadministration of remifentanil and lidocaine.

The effect of remifentanil and lidocaine on time interval acquired for successful tracheal intubation in inhalational induction using sevoflurane / 대한마취과학회지

BACKGROUND: This study was conducted to investigate the optimal time interval for tracheal intubation and the effect of adjuvant drugs such as remifentanil and lidocaine during induction and tracheal intubation using sevoflurane inhalation without muscle relaxant. METHODS: This study enrolled patients with the age of 20-60 years old and ASA 1 or 2. Patients were randomly assigned into one of 4 groups (S, SR, SRL, SL), in which they were given remifentanil (R) i.v. at a rate of 0.25microgram/kg/min, or lidocaine (L) i.v. bolus of 1.5 mg/kg during sevoflurane inhalation (S). Anesthesia was performed as inhalation induction 2 minutes after pre-filling with sevoflurane 8 vol%. The time interval between induction and tracheal intubation was determined using up-and-down method. When satisfied all of the categories of response to tracheal intubation, the case was assigned to 'success', otherwise 'fail'. In each groups, effective time for successful intubation in 50% (ET50) and 95% (ET95) were calculated by probit analysis. RESULTS: ET50 was 3.90 minutes (95% confidence interval 3.32-4.38) in group S, 3.18 minutes (2.92-3.48) in group SL, 2.83 minutes (2.47-3.07) in group SR, and 2.68 minutes (2.37-2.95) in group SRL. In group S, SL, SR, and SRL, ET95 was 4.52 minutes (4.17-7.95), 3.63 minutes (3.37-4.97), 3.30 minutes (3.06-4.64), and 3.12 minutes (2.89-4.42), respectively. CONCLUSIONS: The optimal time to intubate successfully using sevoflurane without muscle relaxant in 95% patients was 4.5 minutes. The optimal time is reduced to 3.1 minutes by coadministration of remifentanil and lidocaine.

Anesthetic Requirements in Chronic Cord-injured Patients Undergoing Surgery below the Level of Injury / 대한마취과학회지

BACKGROUND: We determined the effect of spinal cord injury (SCI) on sevoflurane requirements and stress hormone responses, and sevoflurane concentration to block autonomic hyperreflexia (AHR) in SCI patients. METHODS: In the first series, sevoflurane concentrations to maintain bispectral index score (BIS) at 40-50 and stress hormone response were examined in 27 SCI patients undergoing surgery below the level of injury.Fifteen patients without SCI served as control.Measurements included end-tidal sevoflurane concentrations (ET(SEVO)), systolic blood pressure (SBP), heart rate (HR), catecholamines, vasopressin, and cortisol concentrations.In the second series, sevoflurane concentration to block AHR was examined in 31 SCI patients undergoing transurethral litholapaxy.When a patient developed an episode of AHR, the target sevoflurane concentration was maintained for 10 min, and then the procedure was repeated.Each target concentration was determined by up-down method based on SBP. RESULTS: During surgery, SBP, HR, and BIS were comparable between SCI and control.However, ETSEVO was significantly smaller in the SCI than the control.Plasma concentrations of norepinephrine, epinephrine and cortisol were significantly lower in the SCI than the control.SBP rose by 67 +/- 31 mmHg, whereas HR fell by 13 +/- 8 bpm during the 1st trial in the SCI (P < 0.01).Hypertensive events were associated with increases of norepinephrine concentrations.ETSEVO required to prevent AHR were 3.12% in 50% of patients, 3.83% in 95% of patients. CONCLUSIONS: SCI reduces the anesthetic requirement by 39%, and decreases stress hormone responses during surgery below the level of injury.To prevent AHR in 95% of SCI patients undergoing litholapaxy, ETSEVO 3.83% may be required.

Hemodynamic and Catecholamine Responses to Laryngoscopy and Endotracheal Intubation in Paraplegic Patients: Time Course and Relation to the Affected Level / 대한마취과학회지

BACKGROUND: We determined whether the cardiovascular responses to endotracheal intubation change as a function of the time elapsed after injury and the level of injury in patients with spinal cord injury. METHODS: One-hundred-eighty six patients with complete cord injury were grouped into 3 according to the level of injury:high- (T1-T4, n = 34), mid- (T5-T10, n = 47) and low paraplegics ( 10 yrs.Twenty-five patients with no cord injury served as controls.Systolic arterial blood pressure (SAP), heart rate (HR), and plasma catecholamine concentrations were measured. RESULTS: The intubation caused an increase of SAP and norepinephrine concentrations in every group.However, the magnitude of their peak increases was less in high paraplegics compared with all other groups (P < 0.05).HR was similarly increased in all groups (P < 0.01).Pressure but not either HR or norepinephrine response was enhanced in mid- and low-paraplegics whose injury elapsed more than 10 yrs compared with controls (P < 0.05).The incidence of arrhythmias did not differ among the groups. CONCLUSIONS: The pressure and plasma catecholamine changes associated with endotracheal intubation may be attenuated in high-paraplegics, and the pressure changes may be enhanced over time in mid- and low-paraplegics.

Analgesic Effect of Epidural Fentanyl-Neostigmine after Radical Subtotal Gastrectomy / 대한마취과학회지

BACKGROUND: This study evaluated the efficacy of an epidural single dose of neostigmine combined with fentanyl to provide postoperative analgesia after radical subtotal gastrectomy. METHODS: Fifty two adults patients with ASA physical status 1 and 2 are randomly allocated to receive a single injection of either epidural fentanyl 100 microgramor combination of fentanyl 100microgram with neostigmine 250, 500 and 750microgramin a total volume of 10 ml. Pain scores were recorded after 0, 5, 10, 15, 20, 30 mins to determine the onset of analgesia. Patients' vital signs as well as side effects were monitored at regular intervals. RESULTS: Patients' demographic data were not different from each other. Epidural neostigmine 750 microgram with fentanyl 100 microgram produced effective analgesia (visual analog scale at 10 min ; 35 +/- 10.6 mm). The time to first rescue analgesics administration was significantly longer in the neostigmine group (250 microgram: 84.2 +/- 9.4, 500 microgram: 90.9 +/- 7.1, 750 microgram: 92.5 +/- 14.4 min) than the control group (53.0 +/- 20.0 min). CONCLUSIONS: Combination of fentanyl with neostigmine was proven to be more effective for treating postoperative pain after subtotal gastrectomy than fentanyl alone. Additionally, the most effective dose of epidural neostigmine was 750microgram.

Assessment of Changes in Computerized Neurobehavioral Performance across Multiple Test Sessions / 대한산업의학회지

OBJECTIVE: A cross-sectional study was performed to assess changes in computerized neurobehavioral performance across multiple test sessions for developing a valid performance level and reducing test time. METHODS: The study was conducted on 118 male car painters exposed to low-dose, mixed organic solvents. The study controls were 113 unexposed reference workers matched for age and educational year from different sections of the same factory. Each worker completed a medical and occupational exam and questionnaire. Three tests of the Swedish Performance Evaluation System (5 minutes of Simple Reaction Time, 9 sessions of Symbol Digit, and 4 sessions of Finger Tapping Speed) were administered to each group. RESULTS: The mean age, mean duration of employment, and mean years of education were 33 years, 6.7 years, and 12 years in both groups, respectively. The mean reaction times of the Simple Reaction Time increased with the lapse of time. The known group difference between the exposed and control groups was larger for the first minute than for the successive 3 minutes. Both groups showed improved performance across the first to the seventh sessions on Symbol Digit. Following the seventh session, the performance levels of Symbol Digit had worsened. The t statistic of the two groups was the largest when the two mean reaction times were calculated from the sessions of the fifth to the seventh. In the dominant and non-dominant hands, the number of taps increased and decreased, respectively, across the sessions on Finger Tapping Speed. The known group difference was the largest when comparing the performances from the first to the second sessions. CONCLUSIONS: For valid interpretation and timesaving in computerized neurobehavioral tests, the following is recommended: one practice and one test session for Simple Reaction Time, four practice and three test sessions for Symbol Digit, and one practice and two test sessions for Finger Tapping Speed.

Bispectral Index Values at a Sevoflurane Concentration of 1% in Patients Undergoing Lower Segment Cesarean Delivery: A Comparison between Painful Labor and Painless Labor / 대한마취과학회지

BACKGOUND: An end-tidal concentration of 1% sevoflurane with 50% nitrous oxide (N2O) during a Cesarean section resulted in bispectral index (BIS) values > 60, which are considered at risk for awareness. The present study aimed to determine whether the presence or absence of labor pain prior to the Cesarean section would affect the BIS value. METHODS: Sixty women scheduled to undergo Cesarean section under general anesthesia, were allocated to three groups of 20 patients: women undergoing elective surgery without labor pain (group 1, control), or emergency surgery without (group 2) or with (group 3) active labor pain. After endotracheal intubation, anesthesia was maintained with end-tidal 1% sevoflurane and 50% N2O in oxygen throughout the surgery. The BIS value, systolic blood pressure and heart rate were measured before (baseline) and during the induction of anesthesia, intubation, skin incision, uterine incision, delivery and at 1, 3, 5 and 10 min after delivery. Neonatal effects were assessed using Apgar scores at 1 and 5 min after delivery. RESULTS: BIS values were significantly lower in group 3 than in groups 1 and 2 throughout the study, except at baseline and induction (P < 0.05). However, the systolic blood pressure, heart rate and Apgar scores did not differ among the three groups. CONCLUSIONS: These results demonstrate that 1.0% sevoflurane combined with 50% N2O results in BIS values < 60 during Cesarean delivery in women with active labor pain but not in those without active labor pain, consistent with an adequate depth of anesthesia to prevent recall.

The Proportional Mortality Ratios of Specific-cause Mortality by Occupation and Education among Men Aged 20-64 in Korea (1993-2004) / 예방의학회지

OBJECTIVES: This study investigated the relationship of occupational class and educational background with proportional mortality ratios in Korea. METHODS: Mortality was investigated using the entire registered death data from 1993 to 2004, obtained from the Korean National Statistics Office. Proportional mortality ratios (PMRs) for specific diseases were calculated according to the occupational class and educational background of men aged 20-64. RESULTS: Manual workers were found to have higher PMRs for liver disease and traffic accidents, as did the lower educated group. Especially, this study showed trends of an increasing of the wide gap between lower and higher socioeconomic stati for liver disease, traffic accidents, diabetes mellitus and cerebral vascular disease. The mortality for cerebrovascular disease, diabetes mellitus, heart disease, traffic accident and liver disease showed increasing trends according to the calendar year for the lower than the higher social class. CONCLUSIONS: The specific conditions that had higher PMRs in the Korean lower social class were liver disease and traffic accidents. Especially, there was an increasing trend for a widening of the gap between manual and nonmanual groups in relation to mortality from liver disease, diabetes mellitus and traffic accidents.

Potentiation of Morphine's Antinociception by Group II and Group III Metabotropic Glutamate Receptors Agonists on a Rat Incisional Pain / 대한통증학회지

BACKGROUND: The aim of this study was to clarify the role of spinal groups II and III metabotropic glutamate receptors (mGluRs) with respect to postoperative pain at the spinal level. In addition, the nature of the pharmacological interaction between groups II and III mGluRs agonists and morphine was determined. METHODS: Catheters were inserted into the intrathecal space of male SD rats. To induce postoperative pain, an incision was made in the plantar surface of the hind paw. A pharmacological characteristic for the interaction between groups II and III mGluRs agonists and morphine was evaluated using a fixed-dose analysis. RESULTS: None of intrathecal group II and III mGluRs agonists modified the withdrawal threshold of the incisional pain. The administration of intrathecal morphine resulted in an increase of a dose dependent withdrawal threshold. A fixed-dose analysis revealed that the group III mGluRs agonist, ACPT-III, increased the antinociceptive action of morphine, while the group II mGluRs agonist, APDC, had no effect the antinociception of morphine. CONCLUSIONS: These results suggest that group II and III mGluRs may not play a direct modulatory role in the processing of postoperative pain at the spinal level. However, agonizing group III mGluRs may indirectly contributable to the potentiation of morphines antinociception in the spinal cord. Thus, the combination of morphine and a group III mGluRs agonist may be useful in the management of spinal postoperative pain.

Antinociceptive Effects of Intrathecal Melatonin on Formalin: and Thermal-induced Pain in Rats / 대한통증학회지

BACKGROUND: It has been known that melatonin is involved in the modulation of nociceptive transmission. However, the effect of melatonin administered spinally has not been examined. Therefore, we examined the effect of melatonin on the formalin-induced or thermal-induced nociception at the spinal level. METHODS: Intrathecal catheter was inserted into the subarachnoid space of male Sprague-Dawley rats. Pain was assessed by formalin test (induced by injection of 50microliter of a 5% formalin solution to the hindpaw) or Hot-Box test (induced by radiant heat application to the hindpaw). The effect of intrathecal melatonin was examined on flinching behavior in the formalin test or withdrawal response in Hot-Box test. RESULTS: Intrathecal melatonin produced a limited, but dose-dependent reduction of the flinching response during phase 1 and 2 in the formalin test. In addition, melatonin delivered at evening also decreased the flinching response in both phases of the formalin test. Melatonin restrictively increased the withdrawal latency in Hot-Box test. CONCLUSIONS: These results suggest that melatonin is active against the formalin- and thermal-induced nocicpetion at the spinal level, but the effect is limited.

Comparison of the Effects on Increase of Heart Rate and Blood Pressure between Tracheal Intubation and Desflurane Inhalation during Propofol Anesthesia / 대한마취과학회지

BACKGROUND: This study was undertaken to compare the hemodynamic effects between desflurane inhalation and endotracheal intubation, and to evaluate the intensity of airway irritation by desflurane inhalation of high concentration. METHODS: Twenty adult patients with ASA 1 were enrolled in this study. Radial artery was catheterized and heart rate (HR) and mean arterial pressure (MAP) were measured throughout the study. Anesthesia was induced by propofol and effect site concentration of propofol was maintained at 4microgram/ml using target controlled infusor (TCI). Peak HR and MAP following tracheal intubation were recorded and inhalation of 12 vol% desflurane was started after HR and MAP had been returned to pre-intubation value. The HR, MAP, inspiratory (Fi) and end-tidal fraction (Et) were observed after desflurane inhalation for 10 minutes. RESULTS: The HR and MAP were significantly increased after tracheal intubation and desflurane inhalation, and the peak hemodynamic change after desflurane inhalation was significantly delayed as compared to tracheal intubation. The maximal HR change from baseline after tracheal intubation or desflurane inhalation was not different, but maximal MAP change was significantly lower during desflurane inhalation compared with tracheal intubation. The maximal change of HR and MAP when end-tidal fraction of desflurane had been reached 6 vol% was lower than that of tracheal intubation or desflurane inhalation. CONCLUSIONS: Despite of propofol administration required for general anesthesia, the HR and MAP were significantly increased during desflurane inhalation of high concentration. In particular, the extent of HR increase during desflurane inhalation was similar to that by tracheal intubation.

Comparison of Anesthetic Techniques for Preventing Postoperative Nausea and Vomiting Undergoing Thyroidectomy / 대한마취과학회지

BACKGROUND: The aim of this study was to compare the anesthetic techniques for preventing postoperative nausea and vomiting (PONV) in the patients undergoing thyroidectomy. METHODS: Sixty patients of ASA status I or II, undergoing thyroidectomy were studied. Patients were allocated randomly to one of three groups. Group 1 (n = 22): anesthesia was induced by propofol (2 mg/kg) and maintained with desflurane and 50% nitrous oxide in oxygen. Group 2 (n = 22): anesthesia was induced and maintained propofol and alfentanil using a computer controlled infusion system in 60% medical air in oxygen. Group 3 (n = 16): anesthesia was induced propofol using computer controlled infusion system in combination 50% nitrous oxide in oxygen. The incidence of PONV was assessed at 6 and 24 hours after the surgery and standardized by Rhodes index of nausea, vomiting and retching (RINVR) score. RESULTS: In group 3, the incidence of PONV within the first 6 hours after surgery, was significantly lower as P < 0.05. But, there was no statistical differences among the three groups in the 6 to 24 hours' RINVR score after surgery. CONCLUSIONS: The use of propofol for induction and maintenance with combination 50% N2O is the most effective technique at preventing PONV among the three groups within the first 6 hours after thyroidectomy. This study found no statistically significant difference between the RINVR score, using desflurane-N2O and propofol-alfentanil.

Effects of Gabexate Mesilate (Foy(R)) on Endotoxin-Induced Acute Lung Injury in Rabbit / 대한마취과학회지

BACKGROUND: This study was to clarify the effects of gabexate mesilate (Foy(R)), a synthetic protease inhibitor, on endotoxin induced acute lung injury in rabbit. METHODS: Animals were randomly assigned to one of four groups: saline only (n = 7), saline and Escherichia coli endotoxin 5 mg/kg over 30 mins (n = 7), Foy(R) 1 mg/kg bolus, followed by infusion of Foy(R) at 1 mg/kg/h and endotoxin (n = 7), Foy(R) 2 mg/kg bolus, followed by infusion of Foy(R) at 2 mg/kg/h and endotoxin (n = 7). Infusion of saline or Foy(R) was started 0.5 hour before the start of infusion of saline or endotoxin and continued for 6.5 hours. At the end infusion animals were sacrificed, and the wet to dry (W/D) weight ratio of lung, lung injury score and leukocyte counts, percentage of polymorphonuclear leukocyte (PMNL), and concentrations of albumin and interleukin-8 (IL-8) in bronchoalveolar lavage fluid (BALF) were evaluated. RESULTS: Endotoxin decreased the PaO2 and peripheral blood leukocyte and platelet counts. And it increased the W/D weight ratio of lung, lung injury score and leukocyte counts, percentage of PMNL, and concentrations of albumin and IL-8 in BALF. Foy(R) attenuated all these changes except the decreased peripheral blood leukocyte count. CONCLUSIONS: These findings suggest that Foy(R) attenuates endotoxin-induced acute lung injury in rabbit by inhibiting neutrophil, IL-8 and platelet responses which may play a central role in sepsis related lung injury.

Antinociceptive Effects of Intrathecal Metabotropic Glutamate Receptor Compounds and Morphine in Rats / 대한통증학회지

BACKGROUND: Spinal metabotropic glutamate receptors (mGluRs) and opioid receptors are involved in the modulation of nociception. Although opioid receptors agonists are active for pain, the effects of the compounds for the mGluRs have not been definitely investigated at the spinal level. We examined the effects of the intrathecal mGluR compounds and morphine in the nociceptive test, and then we further clarified the role of the spinal mGluRs. In addition, the nature of the pharmacological interaction after the coadministration of mGluRs compounds with morphine was determined. METHODS: Catheters were inserted into the intrathecal space of male SD rats. For the induction of pain, 50microl of 5% formalin solution or a thermal stimulus was applied to the hindpaw. An isobolographic analysis was used for the evaluation of the drug interaction. RESULTS: Neither group I mGluR compounds nor group III mGluR compounds produced any antinociceptive effect in the formalin test. The group II mGluR agonist (APDC) had little effect on the formalin-induced nociception. The group II mGluR antagonist (LY 341495) caused a dose-dependent suppression of the phase 2 flinching response on the formalin test, but it did not reduce the phase 1 response of the formalin test nor did it increase the withdrawal latency of the thermal stimulus. Isobolographic analysis revealed a synergistic interaction after the intrathecal delivery of a LY 341495-morphine mixture. CONCLUSIONS: These results suggest that group II mGluRs are involved in the facilitated processing at the spinal level, and the combination of LY 341495 with morphine may be useful to manage the facilitated pain state.

A Case of Acquired Digital Fibrokeratoma / 대한피부과학회지

Acquired digital fibrokeratoma is a rare form of benign tumor of the fibrous tissue involving the skin. Histopathologically, the epidermis shows marked hyperkeratosis and acanthosis. The core of lesion is formed by thick, interwoven bundles of collagen predominantly oriented in the direction of the vertical axis of the lesion. We report a case of acquired digital fibrokeratoma in a 50-year-old female who has given consistent trauma on finger tip for corn removal.

A Case of Cronkhite-Canada Syndrome / 대한피부과학회지

The Cronkhite-Canada syndrome is a rare, non-neoplastic, non-hereditary condition which consists of gastrointestinal polyposis associated with alopecia, onychodystrophy and hyperpigmentation of the skin. It usually encountered with severe diarrhea, weight loss and other malabsorption symptoms. The etiology of the condition is unknown. Usually, this syndrome is associated with a poor prognosis due to the effect of malabsorption and generalized debility. We report a case of this syndrome showing unusually rapid improvement after 3-month following only conservative treatment. To our knowledge, this is the first case report of Cronkhite-Canada syndrome in the Karean dermatologic literature.

A Case of Sezary Syndrome / 대한피부과학회지

Patients with idiopathic erythroderma have often been regarded to have a pre-Sezary syndrome because some of them have developed a cutaneous T-cell lymphoma during follow-up. Sezary syndrome is a form of leukemia-lymphoma characterized clinically by erythroderma, pruritus, adenopathy, and circulating atypical cells with cerebriform nuclei. We describe a case of Sezary syndrome in a 40-year-old man, who suffered from idiopathic erythroderma for 3 years. We suggest that close and long-term follow-up should be performed on patients with idiopathic erythroderma.

A Case of Trichoblastic Fibroma

Trichoblastic fibroma is a rare, benign trichogenic tumor that has both an epithelial and mesenchymal component. This tumor may be confused clinically and/or histologically with basal cell carcinoma and other tumors with hair follicle differentiation. We describe here a patient with trichoblastic fibroma on the nose. For further characterization of the tumor, we studied the bcl-2 expression in this case and compared it with those of trichoepitheliomas and basal cell carcinomas. The bcl-2 expression in this case and trichoepitheliomas were positive at the periphery of the tumor nest only, whereas those of basal cell carcinomas were positive diffusely throughout the tumor nest.

The Effects of Immunosuppressants Rapamycin and Cyclosporin A on the Proliferation, Cell Cycle, and Cyclin Expression of Cultured Human Keratinocyte Cell Line HaCaT Cells / 대한피부과학회지

BACKGROUND: Rapamycin and cyclosporin A display an immunosuppressive effect by inhibiting the proliferation of T lymphocytes. Both immunosuppressants are effective in the treatment of psoriasis which is considered to be a T-cell mediated immunological disease. The inhibition of helper T-cells by immunosuppressants is considered to be a therapeutic mechanism on psoriasis. Recent studies have demonstrated that rapamycin and cyclosporin A can directly inhibit the proliferation of many non-hematopoietic cells other than T lymphocytes direct inhibitory effect of two immunosuppressants on keratinocyte proliferation may be another anti-psoriatic mechanism. OBJECTIVE: We investigated the direct inhibitory effects of rapamycin and cyclosporin A on the proliferation of cultured human keratinocyte cell line HaCaT cells without T-cell involvement, and also compared the effects of the two immunosuppressants on the cell cycle and cyclic expression of HaCaT cells. METHODS: The effects of rapamycin and cyclosporin A on the proliferation of cultured human keratinocytes were examined by using the MTS {3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium} method and we also performed a flow cytometric study to determine whether the two immunosuppressants could affect the cell cycle and cyclic expression of HaCaT cells. RESULTS: The results are summarized as follows: 1. Rapamycin and cyclosporin A significantly inhibited the proliferation of cultured human normal keratinocytes and HaCaT cells in a dose-dependent fashion(p<0.05), and the degree of suppression was more evident in normal keratinocytes than in HaCaT cells. 2. Both immunosuppressants reduced the number of HaCaT cells in the S phase and the number of S phase cells was decreased early (Dl) by cyclosporin 4, while rapamycin reduced S phase cells more slowly. 3. The expression of cyclic D2 was significantly inhibited after 16 hours of rapamycin treatment and after 2 hours of cyclosporin A treatment(p<0.05). The expression of cyclic A was significantly suppressed after 2 hours of both immunosuppressant treatments(p<0.05). CONCLUSION: We have shown that rapamycin and cyclosporin A can directly inhibit the proliferation of keratinocytes without T-cell involvement by blocking cell cycle progression in the G1 phase through reducing the number of S phase cells and inhibition of cyclic D2 expression.