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2.
Int Ophthalmol ; 44(1): 297, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38951293

ABSTRACT

BACKGROUND/OBJECTIVES: To evaluate the effect of topical cyclosporine A (CsA) 0.05% in patients with pterygium surgery using fibrin glue (FG). SUBJECTS/METHODS: Patients with primary nasal pterygium were retrospectically analyzed and categorized into two groups: Group 1 with 41 eyes from 38 patients as a control group and group 2 with 39 eyes from 36 patients who received topical CsA twice a day for 6 months. Patients were assessed for recurrence rate, tear film parameters, side effects, and complications at postoperative intervals of 1-7 days; 1st, 3rd, 6th and 12th months. The follow-up period was 1 year. RESULTS: The two groups were age (p = 0.934) and sex (p = 0.996) matched. CsA drop was discontinued in one patient due to burning sensation and conjunctival hyperemia after 1 week. There was no statistically significant difference between the mean preoperative and postoperative 1st year Schirmer I and tear break-up time (TBUT) values in group 1 (p = 0.136; p = 0.069). Although the difference between the mean preoperative and postoperative 1st year TBUT values in group 2 was not statistically different (p = 0.249), Schirmer I results were higher postoperatively (p = 0.003). There was no statistically significant difference between preoperative Schirmer (p = 0.496), postoperative Schirmer (p = 0.661), preoperative TBUT (p = 0.240) and postoperative TBUT (p = 0.238) results of the two groups. Recurrence was observed in only one patient from group 1. CONCLUSION: No recurrent pterygium cases were observed in group 2. Schirmer I values were higher postoperatively in group 2; thus,topical CsA treatment may improve lacrimal secretion and be effective after pterygium surgery with FG.


Subject(s)
Cyclosporine , Fibrin Tissue Adhesive , Immunosuppressive Agents , Pterygium , Humans , Pterygium/surgery , Pterygium/diagnosis , Cyclosporine/administration & dosage , Male , Female , Middle Aged , Fibrin Tissue Adhesive/administration & dosage , Immunosuppressive Agents/administration & dosage , Retrospective Studies , Follow-Up Studies , Adult , Tissue Adhesives/administration & dosage , Tissue Adhesives/therapeutic use , Treatment Outcome , Aged , Ophthalmic Solutions/administration & dosage , Ophthalmologic Surgical Procedures/methods , Ophthalmologic Surgical Procedures/adverse effects , Recurrence , Conjunctiva , Tears/metabolism , Tears/physiology
3.
Yakugaku Zasshi ; 144(7): 775-779, 2024.
Article in English | MEDLINE | ID: mdl-38945852

ABSTRACT

Venetoclax (VEN) is used in patients with acute myeloid leukemia (AML) and is primarily metabolized by CYP3A4, a major drug-metabolizing enzyme. Patients with AML simultaneously administered VEN and CYP3A4 inhibitors require a more appropriate management of drug-drug interactions (DDIs). Here, we report two cases of patients with AML (54-year-old man and 22-year-old woman) administrated VEN and CYP3A4 inhibitors, such as posaconazole, cyclosporine, or danazol. In the first case, we evaluated the appropriateness of timing for adjusting VEN dosage subsequent to the cessation of posaconazole. Consequently, modifying the VEN dosage in conjunction with the cessation of Posaconazole simultaneously may result in elevated plasma VEN levels. In the second case, plasma VEN concentrations were markedly elevated when co-administered with several CYP3A4 inhibitors. Additionally, in vitro assays were conducted for reverse translational studies to analyze CYP3A4 inhibition. CYP3A4 inhibition by combinatorial administration of cyclosporine A and danazol was demonstrated in vitro, which potentially explains the increasing plasma VEN concentrations observed in clinical settings. Although the acquisition of therapeutic effects is a major priority for patients, frequent therapeutic drug monitoring and dosage adjustments considering DDIs would be important factors in chemotherapy.


Subject(s)
Bridged Bicyclo Compounds, Heterocyclic , Cytochrome P-450 CYP3A Inhibitors , Cytochrome P-450 CYP3A , Drug Interactions , Drug Monitoring , Leukemia, Myeloid, Acute , Sulfonamides , Humans , Sulfonamides/administration & dosage , Leukemia, Myeloid, Acute/drug therapy , Cytochrome P-450 CYP3A Inhibitors/administration & dosage , Male , Young Adult , Middle Aged , Bridged Bicyclo Compounds, Heterocyclic/administration & dosage , Bridged Bicyclo Compounds, Heterocyclic/pharmacokinetics , Bridged Bicyclo Compounds, Heterocyclic/blood , Female , Cytochrome P-450 CYP3A/metabolism , Cyclosporine/administration & dosage , Triazoles/administration & dosage , Antineoplastic Agents/administration & dosage
4.
Allergy Asthma Immunol Res ; 16(3): 300-307, 2024 May.
Article in English | MEDLINE | ID: mdl-38910287

ABSTRACT

Severe atopic dermatitis (AD) is not a localized cutaneous disease, but a systemic disease that often accompanies comorbidities. In this nationwide population-based study, we aimed to analyze the prevalence of severe AD and chronic systemic diseases in Koreans aged ≤ 20 years between 2011 and 2019 using the data from the Korean Health Insurance Review and Assessment Service. Total AD and severe AD were defined according to the International Classification of Diseases-10 code L20. In children aged 6-20 years, the prevalence of severe AD significantly increased from 0.02% in 2011 to 0.04% in 2019 (P for trend < 0.001), with the ratio of severe AD to total AD increasing from 0.76% in 2011 to 1.10% in 2019 (P for trend < 0.001). The prevalence rates of severe AD significantly increased between 2011 and 2019 in children aged 6-12 years (P for trend < 0.05) and 13-18 years (P for trend < 0.001). Severe AD was more frequently found in males than in females each year (all P < 0.001, from 2011 to 2019). During the period from 2011 to 2019, the prevalence rate of chronic systemic diseases was higher in subjects with severe AD than in those without AD (P < 0.001) or with mild-to-moderate AD (P < 0.001). In conclusion, our results suggest that the prevalence of severe AD is increasing in Korean children and adolescents and is higher in males and older age groups. Moreover, severe AD is associated with chronic systemic diseases. Therefore, more attention should be paid to managing severe AD.

5.
Iran J Basic Med Sci ; 27(8): 1023-1032, 2024.
Article in English | MEDLINE | ID: mdl-38911250

ABSTRACT

Objectives: The present study aimed to explore the mechanisms underlying the potency of the renoprotective effect of the EtOAc fraction of Limonium duriusculum (EALD) (Plumbaginaceae) against cyclosporine A (CsA), in comparison to vitamin E (Vit. E). Materials and Methods: In the in-vivo experiment, a model of CsA-induced nephrotoxicity was established by dosing male Wistar rats with 25 mg/kg, for 14 days. The protective effect of EALD was investigated through pretreatment of rats with a dose of 200 mg/kg for 14 days, compared to the oral administration of Vit. E at 100 mg/kg. Renal function and markers of oxidative stress were then assessed. Furthermore, a complementary in-vitro study was carried out to evaluate CsA-induced endoplasmic reticulum stress (ERS) and inflammation on cell culture (3T3 cells and MCT cells) using western blot and quantitative RT-PCR.. Results: Pretreatment of rats with EALD significantly attenuated the elevated levels of renal dysfunction markers (BUN, creatinine) and suppressed malondialdehyde (MDA) levels; It also significantly regulated the changes in superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxydase (GPx), and glutathione S-transferase (GST) levels as compared to Vit. E, demonstrating a more effective recovery in renal tissues. Treatment of cells with CsA was linked to the expression of ERS and inflammatory markers activating transcription factor (ATF4), inositol-requiring enzyme 1α (IRE1α), binding immunoglobulin protein (BiP), and monocyte chemoattractant protein-1 (MCP1). In contrast, pretreatment of cells with EALD resulted in a significant decrease in both ERS and inflammatory markers. Conclusion: These findings indicate the renoprotective potential of L. duriusculum, as it demonstrated the ability to ameliorate CsA-induced renal dysfunction through its distinctive antioxidant properties.

6.
Cureus ; 16(5): e59654, 2024 May.
Article in English | MEDLINE | ID: mdl-38836142

ABSTRACT

Good's syndrome is a pathologic condition characterized by thymoma and immunoglobulin disorder. Here, we report a rare case of a patient with Good's syndrome with simultaneous pure red cell aplasia (PRCA) and subclinical myasthenia gravis with detectable serum anti-acetylcholine receptor antibody (AChR Ab). While thymectomy did not result in the improvement of any paraneoplastic syndromes, cyclosporine A (CsA) treatment successfully improved PRCA; however, hypoglobulinemia was not recovered, and anti-AchR Ab did not disappear by CsA treatment in our case. A review of the literature on simultaneous Good's syndrome with PRCA also suggested the efficacy of CsA on PRCA but not hypoglobulinemia, suggesting the distinct underlying mechanisms between these two paraneoplastic symptoms with thymoma. Future research is needed to understand the mechanism underlying this rare pathologic condition and to generate appropriate treatment.

7.
Eye Vis (Lond) ; 11(1): 22, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38872158

ABSTRACT

BACKGROUND: Dry eyes can cause discomfort. To treat dry eye disease, cyclosporine A (CsA) and Lifitegrast are two eye drugs approved by the U.S. Food and Drug Administration (FDA). However, frequent use of eye drops can be challenging and lead to poor compliance, especially in elderly patients. Therefore, this study aimed to develop a drug sustained-release vector and explore its therapeutic effect in animal models of dry eye. METHODS: Firstly, drug membranes loaded with both CsA and Lifitegrast using a carrier called poly(lactate-co-ε-caprolactone) (P(LLA-CL)) were prepared and evaluated for their physicochemical properties, release behavior in vitro, and safety in vivo. Next, a rabbit dry eye model using a 0.1% benzalkonium chloride (BAC) solution was developed and treated by drug-loaded micro membranes. We observed and recorded conjunctival hyperemia, corneal staining, corneal edema, corneal neovascularization, conjunctival goblet cells and hematoxylin and eosin (H&E) staining. Finally, we detected the MUC5AC and MMP-9 by immunofluorescence staining and enzyme-linked immunosorbent assay (ELISA). RESULTS: The composite film released both CsA and Lifitegrast for at least one month. Compared to the blank membrane group, conjunctival hyperemia, corneal fluorescein staining, corneal edema, corneal neovascularization and conjunctival goblet cells recovered faster in the drug membrane group, and the difference was statistically significant. At the molecular level, the drug membrane group showed an increase in mucin density and a significant anti-inflammatory effect. CONCLUSIONS: The implantation of CsA/Lifitegrast loaded P(LLA-CL) membrane under the subconjunctival of the rabbit eye is safe. The study suggests that this subconjunctival administration could be developed into a minimally invasive delivery system to help patients with dry eye disease who require multiple daily eyedrops but have poor compliance.

8.
Molecules ; 29(11)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38893485

ABSTRACT

The following review focuses on the manufacturing and parameterizing of ocular drug delivery systems (DDS) using polymeric materials to create soft contact lenses. It discusses the types of drugs embedded into contact lenses, the various polymeric materials used in their production, methods for assessing the mechanical properties of polymers, and techniques for studying drug release kinetics. The article also explores strategies for investigating the stability of active substances released from contact lenses. It specifically emphasizes the production of soft contact lenses modified with Cyclosporine A (CyA) for the topical treatment of specific ocular conditions. The review pays attention to methods for monitoring the stability of Cyclosporine A within the discussed DDS, as well as investigating the influence of polymer matrix type on the stability and release of CyA.


Subject(s)
Cyclosporine , Drug Liberation , Cyclosporine/chemistry , Humans , Kinetics , Drug Delivery Systems , Contact Lenses, Hydrophilic , Drug Stability , Polymers/chemistry
9.
Clin Ophthalmol ; 18: 1525-1534, 2024.
Article in English | MEDLINE | ID: mdl-38827771

ABSTRACT

Purpose: To evaluate dry eye disease (DED) signs and symptoms six months after a single treatment with Localized Heat Therapy (LHT) (TearCare, Sight Sciences) for patients previously treated for six months with cyclosporine (0.05%) ophthalmic emulsion (CsA) BID (Restasis, Allergan). Setting: Nineteen ophthalmic and optometric practices in 11 US states. Design: Multicenter, cross-over, six month extension to the SAHARA randomized, controlled trial (RCT). Included patients were those randomized to CsA in Phase 1 of the SAHARA RCT. Methods: This was the second phase of the SAHARA RCT in which, following the 6-month endpoint, all patients that had been randomized to CsA discontinued CsA and were treated with LHT and subsequently followed for an additional six months. Outcome measures at 12 months for CsA patients crossed over to LHT included TBUT, OSDI and MGSS. Results: One hundred and sixty-one patients (322 eyes) were analyzed. Mean (SD) baseline TBUT prior to CsA was 4.4 (1.2) seconds, 5.6 (2.6) at 6 months which improved to 6.6 (3.2) and 6.1 (2.8) seconds (both P < 0.001) at 9 and 12 months (3, 6 months post LHT). Mean (SD) OSDI was 50.0 (14.9) at baseline and 34.2 (21.5) after CsA. With LHT at 6 months, this improved to 30.0 (20.6) and 31.0 (19.5) at 9 and 12 months (P = 0.162 vs month 6, P < 0.0001 vs baseline). MGSS was 7.1 (3.2) at baseline, 13.3 (8.2) at the end of CsA treatment which improved to 17.4 (8.8) and 16.1 (9.0) at 9 and 12 months; both P <0.001. Conclusion: SAHARA showed 6-month superiority of LHT to CsA in clinical signs and non-inferiority in symptom scores. This extension shows that patients treated with CsA for 6 months can achieve meaningful additional improvement in signs and symptoms lasting for as long as 6 months following a single LHT treatment without the need for topical prescription therapy.

10.
Article in English | MEDLINE | ID: mdl-38841924

ABSTRACT

Background Psoriasis is a chronic, inflammatory, systemic disease with predominant manifestations in the skin and joints impairing patient's quality of life. A proportion of patients have frequent severe disease exacerbations requiring repeated systemic treatments. There is a scarcity of literature evaluating the role of systemic maintenance therapy in psoriasis patients in preventing such frequent disease flares. Objective To evaluate the efficacy and safety of weekend cyclosporine treatment (WCT) as maintenance therapy in moderate to severe chronic plaque psoriasis patients for the prevention of frequent disease exacerbations. Methods In this retrospective cohort study, 22 psoriasis patients with a history of frequent disease exacerbations (≥ 3 in the last 1 year) who were administered WCT (group A) were compared with the same number of matched patients (age and gender) not on WCT or any systemic maintenance therapy (group B). Results Four patients (18.2%) in group A had disease exacerbations which was significantly lower (p = 0.00, Fisher's exact test) as compared to 21 patients (95.5%) in group B during the study period. Also, patients in group A had significantly lower number of overall exacerbations [mean ± SD: 0.23 ± 0.53 vs 2.95 ± 1.43) p = 0.00, Mann-Whitney U test] as compared to group B. Four (9.1%) patients in group A encountered adverse effects (acneiform eruptions - two, mild gingival hyperplasia - one, myalgia - one) as compared to three (acneiform eruptions - two, headache - one) in group B (p = 1.00). Conclusion WCT significantly reduced the number of disease exacerbations and is a safe and effective mode of maintenance therapy in such subset of psoriasis patients.

11.
Pediatr Nephrol ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834892

ABSTRACT

BACKGROUND: The efficacy of rituximab in steroid-resistant nephrotic syndrome (SRNS) is controversial. We previously reported that rituximab in combination with methylprednisolone pulse therapy (MPT) and immunosuppressants was associated with favorable outcomes. We determined risk factors for poor response following rituximab treatment, which remains unknown. METHODS: This retrospective study included 45 patients with childhood-onset SRNS treated with rituximab across four pediatric kidney facilities. Treatment effects were categorized as complete remission (CR), partial remission (PR), and no remission (NR) at one year after rituximab treatment. The primary outcome was the rate of CR, PR, and NR. Risk factors for non-CR were calculated with multivariate logistic regression. Adverse events and the relationship between disease status at one year and long-term prognosis were also evaluated. RESULTS: The rates of CR, PR, and NR at one year were 69%, 24%, and 7%, respectively. The median time from rituximab administration to CR was 90 days. The median follow-up period after rituximab administration was 7.4 years. In multivariate analysis, significant risk factors for poor response were the pathologic finding of focal segmental glomerular sclerosis and a long interval between SRNS diagnosis and rituximab administration. The rates of CR were 90.3% and 21.4% in patients receiving rituximab within and after 6 months following SRNS diagnosis, respectively (p < 0.001). Five patients developed chronic kidney disease stage G5, including 2 of the 11 patients with PR and all 3 patients with NR, whereas none of the 31 patients with CR developed chronic kidney disease stage G5. CONCLUSION: Early administration of rituximab in combination with MPT and immunosuppressants might achieve favorable outcomes in patients with SRNS.

13.
Cureus ; 16(5): e60875, 2024 May.
Article in English | MEDLINE | ID: mdl-38910697

ABSTRACT

Rhupus syndrome is an autoimmune disorder that combines the symptoms of lupus and rheumatoid arthritis. It is a rare condition that affects the connective tissues of the body such as the joints, muscles, and skin. The symptoms of rhupus syndrome can be similar to those of lupus, including joint pain, fatigue, and skin rashes. However, rhupus syndrome can also cause symptoms of rheumatoid arthritis, such as joint stiffness and swelling. Treatment for rhupus syndrome usually involves a combination of medications and lifestyle changes to manage symptoms and improve the overall quality of life. A 24-year-old female patient was referred by a local physician for evaluation of pancytopenia. Her history dates back to six months when she developed progressive fatigue, dyspnea on mild exertion, and polyarthralgia. Initial laboratory investigations revealed pancytopenia, positive antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA), and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Bone marrow examination confirmed the diagnosis of aplastic anemia. She was started on cyclosporine with an aim to maintain a trough level between 200 and 250 ng/mL. She responded well with hematological recovery in three to four months. This case highlighted the excellent response to cyclosporine hematologically and clinically in rhupus syndrome complicated with aplastic anemia. Further studies are required to establish the long-term efficacy of cyclosporine in this patient population.

14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 841-846, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38926977

ABSTRACT

OBJECTIVE: To analyze the efficacy and influencing factors of cyclosporine (CsA) alone in the treatment of children with acquired aplastic anemia (AA). METHODS: The clinical data of children diagnosed with AA and treated with CsA alone from January 1, 2016 to December 31, 2020 in the Children's Hospital of Chongqing Medical University were collected, and the efficacy and influencing factors of CsA treatment were evaluated. RESULTS: Among the 119 patients, there were 62 male and 57 female, with a median age of 7 years and 1 month. There were 45 cases of very severe AA (VSAA), 47 cases of severe AA (SAA), and 27 cases of non-severe AA (NSAA). At 6 months after treatment, the efficacy of VSAA was lower than that of SAA and NSAA, and there was a statistical difference (P < 0.01). 6 cases died early, 16 cases relapsed, 2 cases progressed to AML and ALL. The results of univariate analysis showed that the high proportion of lymphocyte in the bone marrow at 6 months was an adverse factor for the efficacy of CsA, while high PLT count was a protective factor (P =0.008, P =0.002). The ROC curve showed that the cut-off values of PLT count and the proportion of bone marrow lymphocyte at 6 months were 16.5×109 /L, 68.5%, respectively. Multivariate analysis showed that the high proportion of lymphocyte in bone marrow at 6 months was an independent adverse factor for IST (P =0.020, OR =0.062), and high PLT count was a protective factor (P =0.044, OR =1.038). At 3 months of treatment, CsA response and NSAA were the risk factor for recurrence (P =0.001, 0.031). CONCLUSION: The efficacy of NSAA was higher than that of SAA and VSAA after 6 months of treatment with CsA alone. A high PLT count at the initial diagnosis was a good factor for the effectiveness of CsA, and a high proportion of bone marrow lymphocyte was an unfavorable factor. CsA response at 3 months and NSAA were risk factors for recurrence.


Subject(s)
Anemia, Aplastic , Cyclosporine , Humans , Anemia, Aplastic/drug therapy , Cyclosporine/therapeutic use , Female , Male , Child , Treatment Outcome , Platelet Count , Immunosuppressive Agents/therapeutic use , Child, Preschool , Adolescent , Bone Marrow
15.
Immunol Allergy Clin North Am ; 44(3): 503-515, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38937012

ABSTRACT

Chronic spontaneous urticaria (CSU) affects 0.5% to 1% of the general population and is often managed by allergy and immunology specialists. Guidelines have evolved over the past several decades with an emphasis on decreasing extensive screening laboratory testing as they are of low-yield and cost-ineffective. The utility of biomarkers remains under investigation but total immunoglobulin E may be helpful in determining specific endotypes and response to omalizumab. Antihistamines and omalizumab remain the primary therapeutic options for CSU, but an expanding body of evidence supports the use of immunosuppressants and anti-inflammatory medications in refractory cases.


Subject(s)
Chronic Urticaria , Humans , Chronic Urticaria/diagnosis , Chronic Urticaria/therapy , Chronic Urticaria/drug therapy , Disease Management , Omalizumab/therapeutic use , Biomarkers , Histamine Antagonists/therapeutic use , Anti-Allergic Agents/therapeutic use , Immunoglobulin E/immunology , Immunosuppressive Agents/therapeutic use
16.
Toxicol Mech Methods ; : 1-12, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937256

ABSTRACT

Cyclosporine A (CsA) has shown efficacy against immunity-related diseases despite its toxicity in various organs, including the liver, emphasizing the need to elucidate its underlying hepatotoxicity mechanism. This study aimed to capture the alterations in genome-wide expression over time and the subsequent perturbations of corresponding pathways across species. Six data from humans, mice, and rats, including animal liver tissue, human liver microtissues, and two liver cell lines exposed to CsA toxic dose, were used. The microtissue exposed to CsA for 10 d was analyzed to obtain dynamically differentially expressed genes (DEGs). Single-time points data at 1, 3, 5, 7, and 28 d of different species were used to provide additional evidence. Using liver microtissue-based longitudinal design, DEGs that were consistently up- or down-regulated over time were captured, and the well-known mechanism involved in CsA toxicity was elucidated. Thirty DEGs that consistently changed in longitudinal data were also altered in 28-d rat in-house data with concordant expression. Some genes (e.g. TUBB2A, PLIN2, APOB) showed good concordance with identified DEGs in 1-d and 7-d mouse data. Pathway analysis revealed up-regulations of protein processing, asparagine N-linked glycosylation, and cargo concentration in the endoplasmic reticulum. Furthermore, the down-regulations of pathways related to biological oxidations and metabolite and lipid metabolism were elucidated. These pathways were also enriched in single-time-point data and conserved across species, implying their biological significance and generalizability. Overall, the human organoids-based longitudinal design coupled with cross-species validation provides temporal molecular change tracking, aiding mechanistic elucidation and biologically relevant biomarker discovery.

18.
Diagnostics (Basel) ; 14(12)2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38928687

ABSTRACT

Vernal keratoconjunctivitis is a persistent allergic ocular disease predominantly mediated by the T-helper 2 lymphocyte-associated immune response. The standard therapeutic approaches for vernal keratoconjunctivitis include topical corticosteroids and immunosuppressive eye drops. However, managing vernal keratoconjunctivitis with only topical treatments becomes challenging during seasonally exacerbated periods. Systemic treatments such as oral corticosteroids or cyclosporine may be alternative options. Recently, dupilumab's efficacy in refractory vernal keratoconjunctivitis treatment has been documented. Here, we report a case of refractory vernal keratoconjunctivitis coexisting with atopic dermatitis that rapidly improved after upadacitinib administration. An 18-year-old Japanese woman presented with atopic dermatitis, vernal keratoconjunctivitis, and hay fever. In winter, the patient experienced widespread erythema and escalated itching, leading to significant discomfort and insomnia. Owing to the difficulty in maintaining her current regimen, upadacitinib (15 mg), a Janus kinase inhibitor was initiated. After upadacitinib administration, the treatment-resistant vernal keratoconjunctivitis and erythema improved. Upadacitinib is beneficial in severe cases of atopic dermatitis. Consequently, in our case, upadacitinib may offer therapeutic benefits for refractory vernal conjunctivitis by improving the T-helper 1/2 type immune response, autoimmunity, and oxidative stress. To our knowledge, this is the first report suggesting the potential utility of upadacitinib in managing severe vernal conjunctivitis.

19.
Mod Rheumatol Case Rep ; 8(2): 352-356, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38780240

ABSTRACT

Kikuchi-Fujimoto disease (KFD) is an inflammatory disease of unknown aetiology characterised by fever and cervical lymphadenopathy. Although KFD is a self-limiting disease, patients with severe or long-lasting course require glucocorticoid therapy. We presently report a 17-year-old boy with KFD who had seven relapses since the onset at 4 years old. He suffered from hypothermia, bradycardia, and hypotension during the treatment with prednisolone or methylprednisolone. All of his vital signs recovered after cessation of the drug in addition to fluid replacement and warming. Thus, glucocorticoid was effective but could not be continued because of the adverse event. Although hypothermia developed during the treatment with 5 mg/kg/day of cyclosporine A (CsA) at his second relapse, he was successfully treated with lower-dose CsA (3 mg/kg/day). Thereafter, he had five relapses of KFD until the age of 12 years and was treated by 1.3-2.5 mg/kg/day of CsA. Hypothermia accompanied by bradycardia and hypotension developed soon after concomitant administration of ibuprofen at his fifth and sixth relapses even during low-dose CsA therapy. Conclusively, glucocorticoid, standard dose of CsA, or concomitant use of non-steroidal anti-inflammatory drugs may cause hypothermia, bradycardia, and hypotension and needs special attention. Low-dose CsA could be a choice for such cases with KFD.


Subject(s)
Bradycardia , Cyclosporine , Glucocorticoids , Histiocytic Necrotizing Lymphadenitis , Hypotension , Hypothermia , Humans , Male , Bradycardia/chemically induced , Bradycardia/diagnosis , Bradycardia/etiology , Cyclosporine/adverse effects , Cyclosporine/therapeutic use , Cyclosporine/administration & dosage , Adolescent , Glucocorticoids/therapeutic use , Glucocorticoids/adverse effects , Glucocorticoids/administration & dosage , Hypotension/chemically induced , Hypotension/etiology , Hypothermia/chemically induced , Hypothermia/diagnosis , Histiocytic Necrotizing Lymphadenitis/diagnosis , Histiocytic Necrotizing Lymphadenitis/complications , Histiocytic Necrotizing Lymphadenitis/drug therapy , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Methylprednisolone/administration & dosage , Methylprednisolone/therapeutic use , Methylprednisolone/adverse effects , Prednisolone/administration & dosage , Prednisolone/therapeutic use , Prednisolone/adverse effects , Recurrence
20.
Sci Rep ; 14(1): 12540, 2024 05 31.
Article in English | MEDLINE | ID: mdl-38822034

ABSTRACT

Cyclosporine A (CyA) holds significant importance as a strategic immunosuppressive drug for organ transplant patients. In this study, we aimed to produce pure and cost-effective Cyclosporine A (CyA) by fermenting a culture medium containing dairy sludge, using Tolypocladium inflatum PTCC 5253. Following the fermentation stage, ethyl acetate extraction and fast protein liquid chromatography were employed for sample purification. The initial evaluation of the effectiveness of CyA obtained from these processes was performed through bioassay, wherein the antimicrobial clear zone diameter was found to be larger compared to the sample obtained from the fermentation culture. The concentration of CyA was determined using high-performance liquid chromatography, yielding values of 334 mg/L, 456 mg/L, and 578 mg/L for the fermented, extracted, and purified samples, respectively. Further analysis utilizing liquid chromatography tandem mass spectrometry (LC/MS/MS) confirmed a purity of 91.9% and proper agreement with the standard sample based on the ion intensity of Z/m 1205. To validate the structure of CyA, nuclear magnetic resonance spectroscopy, Fourier-transform infrared (FT-IR), and Raman spectroscopy were employed. X-ray diffraction and differential scanning calorimetry analyses demonstrated that the purified CyA exhibited a crystal structure similar to the standard sample, characterized by two broad peaks at 2θ = 9° and 20°, and comparable glass transition temperatures (57-68 °C for the purified sample; 53-64 °C for the standard sample). Dynamic light scattering analysis confirmed a uniform particle size distribution in both the purified and standard samples. The zeta potentials of the purified and standard samples were determined to be - 25.8 ± 0.16 and - 23.63 ± 0.12 mV, respectively. Our results demonstrate that dairy sludge can serve as a suitable culture medium for the production of (CyA).


Subject(s)
Cyclosporine , Fermentation , Industrial Waste , Cyclosporine/chemistry , Industrial Waste/analysis , Hypocreales/chemistry , Hypocreales/metabolism , Agriculture , Chromatography, High Pressure Liquid , Tandem Mass Spectrometry , X-Ray Diffraction , Spectroscopy, Fourier Transform Infrared
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