• Archives of Pharmacal Research
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• 제19권2호
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• pp.137-142
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• 1996

Effects of plantago-mucilage A (P-MA) on the immune responses were studied in ICR mice. Mice were divided into 4 groups (10 mice/group), and P-MA at doses of 7, 21 and 63 mg/kg were orally administered to mice once a day for 21 consecutive days. Mice were immunized and challenged with sheep red blood cells (SRBC). P-MA at 63 mg/kg/day significantly increased the body weight gain and the relative weights of spleen and thymus, as compared with those in controls. However, there were no significant effects on liver weight due to P-MA treatment. Plaque forming cells (PFC) and hemagglutination (HA) titers to SRBC were significantly enhanced in mice dosed at 21 and 63 mg/kg/day P-MA, as compared with those in controls. Delayed-type hypersensitivity (DTH) reaction to SRBC, phagocyte activity and circulating leukocyte were also significantly increased in mice dosed at 63 mg/kg/day P-MA. These results demonstrate that P-MA markedly enhances both humoral immune and allergic reaction to SRBC at concentrations which don't act on the relative weight of liver.

• Tuberculosis and Respiratory Diseases
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• 제77권3호
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• pp.145-148
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• 2014

Valproic acid is one of the most common antiepileptic drugs used for the treatment of several seizure disorders. A 20-year-old man presented with a sudden decline of consciousness. He had a neurosurgery operation for intracranial and intraventricular hemorrhage. Following surgery, antiepileptic medication was administered to the patient in order to control his seizure events. On valproic acid treatment, he began to complain of fever and dyspnea. His symptoms persisted despite receiving empirical antibiotic treatment. All diagnostic tests for infectious causes were negative. A high-resolution computed tomography scan of the chest revealed predominantly dependent consolidation and ground-glass opacities in both lower lobes. The primary differential was drug associated with interstitial lung disease. Therefore, we discontinued valproic acid treatment and began methylprednisolone treatment. His symptoms and radiologic findings had significantly improved after receiving steroid therapy. We propose that clinicians should be made aware of the potential for valproic acid to induce lung injury.

• 약학회지
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• 제40권3호
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• pp.326-334
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• 1996

Effects of methanol extract of Astragali Radix (AR) on the immune responses were studied using ICR mice. Mice were divided into 4 groups (10mice/group), and methanol extracts of AR at doses of 0.05, 0.25 and 1.25g/kg were orally administered to ICR mice once a day for 2 weeks. Mice were immunized and challenged with sheep red blood cells (SRBC). The results of this study were summarized as follows; (1) Methanol extract of AR at 0.05, 0.25 and 1.25g/kg didn't affect the weight ratios of thymus to body, as compared with those in controls, but significantly increased spleen weight ratio. (2)Methanol extract of AR at 0.05 and 0.25g/kg significantly increased hemagglutination titer and splenic plaque forming cells corresponding to humoral immunity, as compared with those in controls, but their enhancements were somewhat lowered at a high dose (1.25g/kg). (3) Methanol extract of AR at 0.05 and 0.25g/kg siginificantly increased delayed-type hypersensitivity reaction resulted from cell-mediated immunity, as compared with those in controls, but not so significant increases were observed at a high dose (1.25g/kg). (4) Methanol extract of AR at 0.05 and 0.25g/kg significantly increased phagocytic activity and the number of circulating leukocyte compared with those in controls, but their enhancements were lowered at a high dose (1.25g/kg). These results suggest that methanol extract of Astragali Radix increased humoral and cell-mediated immune responses, phagocytic activity and the number of circulating leukocyte, dependent upon dose, but inhibited their enhancement effects were decreased at a high dose (1.25g/kg).

• 약학회지
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• 제40권2호
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• pp.202-211
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• 1996

Experiments were performed on male Sprague-Dawley rats to investigate the immunobiological effects on route of administration of amygdalin(AM). Rats were administered orally at 12.5, 25, or 50mg/kg/day of AM or injected wtih 25,50, or 100mg/kg/day of AM intravenously for 2 weeks. Rats were immunized and challenged with sheep red blood cells(SRBC). The results of this study were summarized as follows;(1) In oral administration of AM, body weight gains were significantly increased by 50mg/kg AM as compared with controls, the relative weights of liver and thymus also were significantly increased by 12.5 and 25mg/kg AM. However, 2-mercaptoethanol-resistant hemagglutination titier (2-MER HA), Plaque forming cells (PFC) and rosette forming cells (RFC) were non-dose dependently decreased. Phagocytic activity and delayed-type hypersensitivity (DTH) reaction also were significantly decreased by 50mg/kg AM. (2) In intravenous injection of AM, body weight gains, hemagglutination titer (HA), 2MER-HA, DTH reaction, PFC, RFC and circulating leukocytes were not influenced by AM. However, the relative weights of liver, spleen and thymus were significantly enhanced 100mg/kg AM. These results indicated that oral administration of AM non-dose dependently suppresses humoral and cell-mediated immunity in SD rats, and that intravenous injection of AM is unaffected humoral and cell-mediated immunity, however, the high dose of it significantly enhances phagocytic activity.

• 한국임상약학회지
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• 제20권2호
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• pp.128-137
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• 2010

This review summarizes gender differences in pharmacokinetics, pharmacodynamics, and adverse drug reactions. Gender differences in pharmacokinetics are categorized by four major factors: absorption/bioavailability, distribution, metabolism, and elimination. There are sex-based differences in gastric emptying time, gastric alcohol dehydrogenase activity, apparent volume of distribution, ${\alpha}1$-acid glycoprotein level, phase I (CYP) and phase II metabolizing enzymes, glomerular filtration rate, and drug transporters. This review also reports gender differences in pharmacokinetics and pharmacodynamics of cardiovascular agents, central nervous system acting agents and antiviral agents. In addition, it has been reported that females experience more adverse reactions such as coughing, tachycardia, nausea, vomiting, rash, hypersensitivity, hepatotoxicity, and metabolic disorder after taking cardiovascular, central nervous system acting and antiviral agents. Therefore, in order to provide optimal drug dosage regimens both in male and female, gender differences in pharmacokinetics, pharmacodynamics, and adverse drug reactions must be considered.

• Tuberculosis and Respiratory Diseases
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• 제59권4호
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• pp.423-426
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• 2005

Imatinib-mesylate는 만성 골수성 백혈병과 소화기 위장관 기질암의 효과적인 치료제로 인정되면서 사용량이 급격하게 증가하고 있다. Imatinib-mesylate로 치료 중 발생하는 기침이나 호흡곤란은 대부분 폐부종이나 흉수, 간질성 폐질환에 의하여 발생하며, 간질성 폐질환의 경우 조직학적으로는 비특이적 간질성 폐렴, 과민성 폐렴, 호산구 침착 등의 형태로 발생한다. 그러나 imatinib-mesylate에 의하여 간질성 폐질환이 발생하는 기전은 아직 알려져 있지 않다. 치료는 대부분 imatinib-mesylate를 중단하거나 부신피질호르몬제를 사용한 후 호전된다. Imatinib-mesylate를 사용하는 경우 호흡기계에 발생하는 부작용에 대한 관찰이 필요할 것이다. 저자들은 위장관 기질암으로 imatinib-mesylate를 복용하던 중 발생한 과민성 폐렴을 경험하여 보고하는 바이다.

• Biomolecules & Therapeutics
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• 제28권5호
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• pp.456-464
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• 2020

Mast cells (MCs) are systemically distributed and secrete several allergic mediators such as histamine and leukotrienes to cause type I hypersensitivity. Dasatinib is a type of anti-cancer agent and it has also been reported to inhibit human basophils. However, dasatinib has not been reported for its inhibitory effects on MCs or type I hypersensitivity in mice. In this study, we examined the inhibitory effect of dasatinib on MCs and MC-mediated allergic response in vitro and in vivo. In vitro, dasatinib inhibited the degranulation of MCs by antigen stimulation in a dose-dependent manner (IC₅₀, ~34 nM for RBL-2H3 cells; ~52 nM for BMMCs) without any cytotoxicity. It also suppressed the secretion of inflammatory cytokines IL-4 and TNF-α by antigen stimulation. Furthermore, dasatinib inhibited MC-mediated passive cutaneous anaphylaxis (PCA) in mice (ED₅₀, ~29 mg/kg). Notably, dasatinib significantly suppressed the degranulation of MCs in the ear tissue. As the mechanism of its effect, dasatinib inhibited the activation of Syk and Syk-mediated downstream signaling proteins, LAT, PLCγ1, and three typical MAP kinases (Erk1/2, JNK, and p38), which are essential for the activation of MCs. Interestingly, in vitro tyrosine kinase assay, dasatinib directly inhibited the activities of Lyn and Fyn, the upstream tyrosine kinases of Syk in MCs. Taken together, dasatinib suppresses MCs and PCA in vitro and in vivo through the inhibition of Lyn and Fyn Src-family kinases. Therefore, we suggest the possibility of repositioning the anti-cancer drug dasatinib as a treatment for various MC-mediated type I hypersensitive diseases.

• 한국임상약학회지
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• 제27권3호
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• pp.143-149
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• 2017

Background: L-asparaginase (L-ASP) is a critical agent for the treatment of acute lymphoblastic leukemia and lymphoma, which is associated with serious toxicities including hypersensitivity, pancreatitis and thrombosis. Methods: To evaluate the toxicity of L-ASP in real clinical settings, we included the patients with L-ASP adverse drug reactions (ADRs) reported in a regional pharmacovigilance center of Seoul St. Mary's hospital from January 2014 to December 2015. Results: A total of 83 cases of L-ASP related ADRs were reported in 54 patients. Of these 83 cases, 65 cases (78.3%, 65/83) were spontaneously reported and 18 cases (21.7%, 18/83) were detected by further medical records review. Of the patients with ADRs, pediatric patients accounted for 83.3% of the cases (45/54) and median age was 9 years. The most common clinical manifestations of ADRs were hematology manifestations (31.3%, 26/83), followed by hepatobiliary manifestations (18.1%, 15/83). Thirty-four serious ADRs were reported in 19 patients. The sserious ADR group showed significantly longer hospitalization and higher rate of discontinuation of L-ASP than the non-serious ADR group (p = 0.005, 0.03). The most common clinical manifestations of serious ADRs were hepatobiliary manifestations (41.2%, 14/34). In total, 8 cases (9.6%, 8/83) of unlabeled ADRs were identified. They were serious ADRs. Conclusion: We identified unlabeled serious ADRs of L-ASP. Also, correlations were observed between serious ADRs and length of hospitalization, discontinuation rate respectively. Further investigations and developed spontaneous ADR reporting systems are needed to evaluate these correlations.

• Archives of Plastic Surgery
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• 제47권4호
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• pp.297-300
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• 2020

Hyaluronidase, an enzyme that breaks down hyaluronic acid, has long been used to increase the absorption of drugs into tissue and to reduce tissue damage in cases of extravasation of a drug. With the increasing popularity of hyaluronic acid filler, hyaluronidase has become an essential drug for the correction of complications and unsatisfactory results after filler injection. For this reason, when performing procedures using hyaluronic acid filler, a sufficient knowledge of hyaluronidase is required. In order for hyaluronidase to dissolve a hyaluronic acid filler, it must interact with its binding sites within the hyaluronic acid. The reaction of a filler to hyaluronidase depends on the hyaluronic acid concentration, the number of crosslinks, and the form of the filler. Hyaluronidase is rapidly degraded and deactivated in the body. Therefore, in order to dissolve a hyaluronic acid filler, a sufficient amount of hyaluronidase must be injected close to the filler. If the filler is placed subcutaneously, injection of hyaluronidase into the filler itself may help, but if the filler is placed within a blood vessel, it is sufficient to inject hyaluronidase in the vicinity of the vessel, instead of into the filler itself. Allergic reactions are a common side effect of hyaluronidase. Most allergic reactions to hyaluronidase are local, but systemic reactions may occur in infrequent cases. Since most allergic responses to hyaluronidase are immediate hypersensitivity reactions, skin tests are recommended before use. However, some patients experience delayed allergic reactions, which skin tests may not predict.

• 약학회지
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• 제48권6호
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• pp.335-344
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• 2004

Interleukin-2 (IL-2), a glycoprotein mainly secreted by CD4+ T helper Iymphocytes, has been developed to use recombinant cytokine to augment the immune response against cancer since IL-2 not only stimulates T Iymphocytes but also enhances natural killer (NK) cell activity. In order to evaluate the immunological safety of recombinant mouse IL-2 (rmIL-2) in cancer therapy, renal cell carcinoma was established in the flank by s.c. injection of renca cell line. Tumor-bearing BALB/c mice were treated with I.p. injections with $2{\times}10^5$ Lu rmIL-2. Even though the tumor size was diminished, there were not significant recovery of body and relative lymphoid organ weights including thymic atrophy in rmIL-2 immunotherapy. Distribution ratios of T cell subsets in thymus were analysed using flow cytometry. Without regard to dosage of rmIL-2, the ratio of CD3+CD4-CD8- T cells was increased in accordance with survival of solid tumor but that of CD4+CD8+ T cells was decreased dramatically. Emergence of autoantibodies (ANA, anti-dsDNA, and anti-histone) in blood was measured after rmIL-2 treatment. The results showed that the levels of ANA and anti-dsDNA did not significantly changed, but the level of anti-histone was increased significantly owing to rmIL-2 therapy. These results indicate rmIL-2 immunotherapy is to induce the autoimmune potential, and the anti-histone measurement as a biomarker of autoimmunity is useful in cancer immunotherapy.