Usage Of Cyclophosphamide Research Articles

Exploring the interplay of MTHFR and FGG polymorphisms with serum levels of adiponectin and leptin in pediatric lupus nephritis: a pilot study

BackgroundAdiponectin and leptin are pivotal in the regulation of metabolism. Pediatric lupus nephritis (pLN), a manifestation of childhood systemic lupus erythematosus (SLE) affecting the kidneys, is associated with impaired adipokine levels, suggesting a role in pLN pathogenesis. The aim of this study was to explore the potential relationship between specific single-nucleotide polymorphisms (SNPs)—methylenetetrahydrofolate reductase (MTHFR) rs1801131 and fibrinogen gamma chain (FGG) rs2066865—and the serum levels of leptin and adiponectin in patients with pLN.MethodsNinety-eight pLN patients and one hundred controls were enrolled in the study. Serum leptin and adiponectin levels were measured using ELISA. DNA extraction and real-time PCR genotyping were performed for MTHFR rs1801131 and FGG rs2066865 SNPs.ResultsCompared to healthy controls, pLN patients exhibited significantly greater serum leptin (11.3 vs. 18.2 ng/mL, p < 0.001) and adiponectin (18.2 vs. 2.7 ug/mL, p < 0.001). Adiponectin levels were positively correlated with proteinuria (p < 0.05), while leptin levels positively correlated with proteinuria, SLE disease activity index-2000 (SLEDAI-2K), and cyclophosphamide usage (all p < 0.05). There was no significant association between MTHFR rs1801131 or FGG rs2066865 SNPs and pLN in either codominant or allelic models (all p > 0.05). However, the AG genotype of FGG gene rs2066865 SNP was significantly associated with high leptin levels (> 15 ng/mL) (p = 0.01).ConclusionSerum adiponectin and leptin levels are associated with pathological manifestations of pLN. High leptin levels are associated with the AG genotype of FGG rs2066865 SNP in pLN patients, suggesting direct involvement in disease progression and potential utility as a disease biomarker.

L-carnitine fails to rescue chemotherapy injured ovaries by epigenetic changes of transcription factors

Cyclophosphamide (CP), as an anti-cancer drug, is frequently used to treat various types of cancer. A decreased number of ovarian follicles impaired normal ovarian function, and subsequent premature ovarian failure (POF) presented as a side effect of cyclophosphamide usage. These events may eventually affect the fertility rate of individuals. The present study showed the effect of cyclophosphamide on ovarian reserves and the protective effect of L-carnitine (LC) as an antioxidant to prevent POF.To design the study, six to eight-week-old NMRI female mice were divided into three groups: control, cyclophosphamide (CP), and cyclophosphamide + L-carnitine (CP + LC). Mice received drugs intraperitoneally (IP) for 21 days. In the following 24 h after the last injection, both ovaries were used to evaluate the expression of Sohlh1 and Lhx8 genes by Real-time PCR. Furthermore, the alteration of Lhx8 promoter methylation was examined by Methylation-sensitive high-resolution melting analysis (MS-HRM).The present data showed the negative effect of CP on regulator genes of oogenesis including Sohlh1 and Lhx8. In addition, an examination of the epigenetic status of the Lhx8 gene showed a change in promoter methylation of this gene following cyclophosphamide injection. Although, L-carnitine is an effective antioxidant in relieving oxidative stress caused by cyclophosphamide and its damage, in the present study, however, the use of L-carnitine failed to protect the ovaries from changes caused by CP injection. So, using cyclophosphamide can alter the expression of folliculogenesis genes through its effects on epigenetic changes and may cause POF. The results of the present study showed that L-carnitine consumption can’t protect the ovaries against the adverse effects of CP.

Cytoprotective effects of cinnamaldehyde and adipoRon against cyclophosphamide‐induced cardio-renal toxicity in rats: Insights into oxidative stress, inflammation, and apoptosis

Cyclophosphamide is an alkylating agent used in the treatment of various types of tumors and autoimmune diseases. Unfortunately, cyclophosphamide usage is limited in clinical situations due to its cardio-renal toxicity. The current study investigates the protective effects of cinnamaldehyde and adipoRon against cyclophosphamide-induced cardio-renal toxicity. 24 adult male Sprague-Dawley rats were assorted in a random manner into 4 groups; control, cyclophosphamide, cyclophosphamide+cinnamaldehyde (90 mg/kg) and cyclophosphamide+adipoRon (25 mg/kg), rats treated with cinnamaldehyde and adipoRon for 10 days and on the 7th day of the experiment, rats were given a single I.P. injection of cyclophosphamide (200 mg/kg). Thereafter, specimens of heart and kidney tissues were used for biochemical, immunohistochemical and histopathological analysis. Cinnamaldehyde and adipoRon attenuated the cardio-renal intoxication induced by cyclophosphamide which was manifested by a marked decrease in cardiac-renal injury markers (CK-MB, LDH, cTnI, serum creatinine and blood urea nitrogen) accompanied with normalization of histopathological changes. Moreover, cinnamaldehyde and adipoRon reversed cardio-renal oxidative stress, inflammation, and apoptosis as they have significantly decreased 8-OHdG levels, MDA contents, NF-κB, TNF-α and caspase-3 expression. On the other hand, cinnamaldehyde and adipoRon have upregulated antioxidant biomarkers; GSH concentration, Nrf2 expression as well as the anti-inflammatory cytokine; IL-10 and the antiapoptotic; BCL2. In conclusion, these cytoprotective effects of cinnamaldehyde and adipoRon suggesting the possibility of using them in combination with cyclophosphamide treatment protocols to minimize their unwanted side effects.

Predictors of Avascular Necrosis in a Cohort of Egyptian Systemic Lupus Erythematosus Patients: Retrospective Two Centers Study.

Avascular necrosis is a common complication in patients with SLE. This study aimed to investigate the risk factors for the occurrence of avascular necrosis among SLE patients receiving steroid therapy at various doses in combination with immunosuppressants. In this retrospective study, the medical records of all SLE patients under follow-up at the outpatient clinics of Cairo and Kafr Elsheikh University hospitals through the period from November 2014 to August 2019 were included. Avascular necrosis was diagnosed by the findings of different imaging modalities. We retrieved the medical records of 770 SLE patients during the study period; of them, 55 patients (7.1%) had avascular necrosis. There was significant higher usage of cyclophosphamide (p = 0.003), total cumulative dose of steroids 15-35g plus immunosuppressants (p < 0.001), and steroids >35g plus immunosuppressants (p = 0.016) in the avascular necrosis cohort. Based on the univariate analysis, disease duration of more than five years and cumulative use of steroids were statistically significant predictors for the evolvement of avascular necrosis. Multivariate logistic regression analysis revealed that a disease duration of more than five years was associated independently with avascular necrosis. Our data seem to show a role of the association of immunosuppressants plus steroids in the risk of developing avascular necrosis.

Antifungal resistance and clinical significance in small animals

In conjunction with the increasing number of immunosuppressive diseases in human and animal populations, fungal diseases have also been rising. Despite the introduction of new antifungal agents in recent years, the incidence of fungal infections continues to increase, and subsequently, the prevalence of resistance to these drugs is remarkably increased, posing significant health concerns. While antifungal drug resistance is of great importance in human medicine, especially against Candida spp., there are few studies about antifungal resistance in veterinary medicine. Indeed, several fungal infections in dogs have been reported, especially in cases of neutropenia associated with the usage of cyclophosphamide or parvoviral enteritis infection. ketoconazole, fluconazole, itraconazole, and terbinafine, the mainly used antifungal drugs in treating dermatomycosis, have been encountered in feline and canine medicine. However, it has been reported that the desired success could not be obtained from the treatments applied in various cases in recent years. This review aimed to emphasize the role of the development of resistance against antifungal agents on treatment failures. In this context, monitoring of antifungal resistance in veterinary clinics and animal facilities by veterinarians and other animal health authorities is recommended

The effect of cyclophosphamide combined with zinc on male mice Mus musculus spermatozoa

Background: The usage of cyclophosphamide leads to infertility of reproductive system caused by acrolein. Acrolein can itself cause oxidative damage by depletion of cellular glutathione (GSH) by conjugation, leading to membrane disruption, DNA and mitochondrial damage and can exacerbate apoptosis, which may affect spermatogenesis. Zinc (Zn) which is constituents of superoxide dismutase, has a protective effect towards free radicals from physiological or pathologic effects to minimize the cell’s damage. &#x0D; Objective: The purpose of this research was to know the effect of Zn on the spermatozoa count of Mus musculus that was given cyclophosphamide intraperitoneally.&#x0D; Methods: In the present study, cyclophosphamide was administered in saline 200 mg/kg 1x weekly for 5 weeks by ip route, whereas Zn was supplemented by oral route with doses of 25, 50, 100 mg/Kg/day for 5 weeks. The data were analyzed with Anova and followed by Bonferroni Test at a significant level of 5%.&#x0D; Results: The result of this research revealed that high Zn diet and Cp administration decrease sperm count simultaneously. It showed by the decrease of sperm count from 1490 (1 x 103)/ml sperm in the control group becomes 240 (1 x 103)/ml sperm in treatment group with 100 mg/kg of oral Zn and 200 mg/kg of cyclophosphamide.&#x0D; Conclusion: This research shows that Zn supplement to prevent cyclophosphamide toxic effect in spermatogenesis does not have a protective effect, in fact its reduce sperm count by excess of Methallothine production and alter the spermatogenesis by reduce Cu intake from intestine.

Prospective Analysis of Hemorrhagic Cystitis and BK Viremia in Allogeneic Hematopoietic Stem Cell Transplantation

Objective:BK virus (BKV) infection has been shown to be related to hemorrhagic cystitis (HC) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). There are conflicting data regarding the association between BKV titers in plasma and clinical disease as well as the risk factors for BKV-related HC. Our aim is to study the risk factors and relationship with plasma BK viral load for development of HC in a prospective analysis.Materials and Methods:We prospectively evaluated 59 patients who received allo-HSCT between 2014 and 2016 by quantitative BK virus polymerase chain reaction (PCR) (Altona Diagnostics, Germany) from blood samples at days 0, 30, 60, and 90 after allo-HSCT. The patients were monitored for signs and symptoms of HC.Results:HC was diagnosed in 22 patients (37%) at a mean of 100 days (range: 0-367 days). In multivariate analysis, the usage of cyclophosphamide (sub-distribution hazard ratio [sdHR]: 7.82, confidence interval [CI]: 1.375-39.645, p=0.02), reactivated CMV (sdHR: 6.105, CI: 1.614-23.094, p=0.008), and positive BKV viremia (sdHR: 2.15, CI: 1.456-22.065, p=0.01) significantly increased the risk of developing HC. Patients with higher viral loads at day 30 and day 60 were diagnosed with more severe HC (p<0.001). Median BK viral loads of >101.5 copies/mL at day 0 (sensitivity 0.727, specificity 0.875), >98.5 copies/mL at day 30 (sensitivity 0.909, specificity 0.875), and >90.0 copies/mL at day 60 (sensitivity 0.909, specificity 0.875) were indicative of HC.Conclusion:Our study showed that administration of cyclophosphamide, CMV reactivation, and BK virus positivity were associated with HC. Plasma BK virus PCR titers at days 0, 30, and 60 after transplant were sensitive tools for predicting clinically proven HC.

Comparisons of Clinical Features in Japanese Patients with Behçet’s Uveitis Treated in the 1990s and the 2000s

ABSTRACTPurpose: We investigated clinical characteristics of ocular Behçet’s disease (BD) patients treated in the 1990s and the 2000s.Methods: We retrospectively examined records of 68 newly arrived patients with ocular BD followed for more than 4 months during the 2000s and compared to those of 107 patients during the 1990s. Patient profiles, ocular and systemic symptoms, frequency of ocular attacks, BD ocular attack score 24–6 months (BOS24-6M), best-corrected visual acuity (BCVA), and immunomodulatory treatment were noted.Results: Clinical characteristics in the 2000s showed increases in iridocyclitis type, intestinal-, vasculo-, and neuro-BD cases, oral corticosteroid, methotrexate, and infliximab therapy usage, cataract and glaucoma surgery, and pseudophakia, and decreases in BOS24-6M and cyclophosphamide usage. BCVA of 20/30 or better at the final visit was slightly increased in the 2000s.Conclusions: Milder ocular BD tendency was seen in cases in the 2000s, whereas the incidence of special type of BD might be increasing.

Safety of Cyclophosphamide Therapy in Autoimmune Rheumatic Diseases

Cyclophosphamide (CYC) is one of the most potent antineoplastic and immunosuppressant agents. It is used as a drug of choice in many organ-threatening manifestations of systemic autoimmune rheumatic diseases (AIRDs) such as lupus nephritis, antineutrophil cytoplasmic antibody-associated vasculitis, classical polyarteritis nodosa, and myositis. It is also used in connective tissue disease-related interstitial lung disease and Behcet's disease. However, its use may be limited by the toxicities including its adverse effects on gonads in the childbearing age group, severe infections, hemorrhagic cystitis, and malignancies associated with prolonged usage. As a result, mycophenolate, azathioprine, and rituximab have gained popularity over CYC as an induction and maintenance agent in many AIRDs. However, in the event of failure of aforementioned agents in aggressive rheumatic diseases or in a resource-limited setting, the usage of CYC continues to be a useful therapeutic strategy. In this review, we have appraised the adverse effects of CYC therapy in AIRDs which would help clinicians in taking informed decisions regarding CYC usage.

Histological and immunohistochemical study of cyclophosphamide effect on adult rat testis

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Nowadays, cyclophosphamide is widely used as anticancer and immunosuppressive agent in various drug regimens in many diseases and in young and old age. The aim of this research is to study the possible histological changes that may occur in the testes of adult male albino rats as a result of chronic exposure to cyclophosphamide and the prognosis of this effect.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; Thirty healthy adult male albino rats were used in this study. They were equally divided into three groups; a control, an experimental and a withdrawal groups. The Animals of the experimental group were treated with daily dose of 5 mg/ kg cyclophosphamide orally for successive 28 days. Animals of the withdrawal group were left without treatment and sacrificed after 28 days from the last dose of cyclophosphamide. At the time of sacrifice, all animals were anesthetized by ether inhalation and their testes were dissected out carefully and processed for light and electron microscope examinations&lt;span lang="EN-IN"&gt;. &lt;/span&gt;&lt;span lang="EN-IN"&gt; &lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Testes of the cyclophosphamide treated group revealed presence of many distorted shrunken seminiferous tubules which appeared with marked reduction in the thickness of the epithelium and wide lumina. Many germ cells with deeply stained nuclei, giant cells in mitosis and intracellular vacuoles were observed. Cross sections in mid pieces of sperms showed marked affection of axoneme, fibrous sheath and mitochondrial sheath. The cytoplasm of the Leydig cells contained mitochondria, dilated SER, Golgi cisternae and RER. Testes of the withdrawal group showed that the seminiferous tubules still had reduced height of their epithelium with wide intercellular spaces. Abnormal stratification and destructed germinal epithelium were evident with desquamated germ cells. Cross sections of mid pieces of the sperms showed distorted axoneme and swollen mitochondrial sheath. The cytoplasm of leydig cells contained many electron dense granules, RER, many dilated SER and mitochondria.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Chronic cyclophosphamide treatment not only produced serious histological changes of the testis but also in its serological parameter. These changes persisted after cessation of cyclophosphamide administration which indicates the cumulative irreversible toxic effect of cyclophosphamide. So, it is advisable to avoid the usage of cyclophosphamide as possible especially in young patients&lt;span lang="EN-IN"&gt;. &lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt; &lt;/p&gt;

Effects of cyclophosphamide on immune system and gut microbiota in mice

Cyclophosphamide (CP) is the most commonly used drug in autoimmune disease, cancer, blood and marrow transplantation. Recent data revealed that therapy efficacy of CP is gut microbiota-dependent. So, it is very important to understand how CP affects intestinal microbiota and immune function. In this study, the effects of CP on mice immuno-activity were firstly evaluated, then, the fecal microbiota from normal and CP-treated mice was compared, and the characteristic bacterial diversity and compositions were identified, using 454 pyrosequencing technology. The results showed that CP reduced the diversity and shifted the fecal microbiota composition. Specifically, CP treatment decreased the proportion of Bacteroidetes while increased the proportion of Firmictutes in the microbial community. Most importantly, specific microbiota signatures belonging to Bacteroides acidifaciens, Streptococcaceae and Alistipes were also identified, which would provide new insight into the efficacy and side effects in clinical usage of CP. This should be helpful for further demonstration of CP's action mechanism, development of personalized therapy strategies, and prediction of potential side effects related to various treatment regimens of CP.

Hemorrhagic cystitis in children treated with alkylating agent cyclophosphamide: The experience of a medical center in Taiwan

Hemorrhagic cystitis is a common complication with chemotherapeutic alkylating agents. We investigated the possible prognostic factors of cyclophosphamide-induced hemorrhagic cystitis in children. Medical records of children (< 18 years old) with cyclophosphamide-related hemorrhagic cystitis were collected retrospectively from January 2000 to December 2010 in a tertiary care center. We also prospectively enrolled children (< 18 years old) with cyclophosphamide treatment. The retrospective study consisted of 23 patients whose median age was 11 years. The median day of onset time was 1 day after cyclophosphamide usage. The hemato-oncological diseases included acute leukemia (39.1%), lymphoma (13%), blastoma (13%), sarcoma (13%), aplastic anemia (13%), and others (8.7%). Patients who received bone marrow transplantation (BMT) had significantly longer duration of hemorrhagic cystitis than those who did not receive BMT (p < 0.05). Serum uric acid, checked prior to and after the onset of hemorrhage cystitis, was significantly lower after the development of hemorrhagic cystitis (p < 0.05). In the prospective study, 11 children were enrolled with a median age of 5 years. The urinary nitrite/nitrate and 8-iso-prostaglandin F2α levels increased significantly after cyclophosphamide usage (p < 0.05). Alteration serum uric acid level and BMT could be indicators for severe hemorrhagic cystitis. The elevated levels of urinary nitrite/nitrate and 8-iso-prostaglandin F2α may indicate the essential roles played by nitric oxide syntheses and reactive oxidative stress in cyclophosphamide-induced hemorrhagic cystitis. These findings may help clinicians formulate a better strategy for treating cyclophosphamide-induced hemorrhagic cystitis.

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Treatment course of steroid-dependent nephrotic syndrome: Emphasized on treatment effect

Children with steroid-dependent nephrotic syndrome (SDNS) need long-term steroid usage to maintain sustained remission. Cyclophosphamide is a well-known alternative agent to spare the use of steroids and avoid the side-effects that result from long-term steroid therapy. Most children may continue to have SDNS despite receiving cyclophosphamide. Additional alternative drugs may be needed. In the present study, the effects on SDNS of sequential treatment after cyclophosphamide usage were established. Forty-six children with SDNS were enrolled in this retrospective uncontrolled study. In addition to prednisolone, patients were treated with cyclophosphamide as a first-line alternative drug. Children who still had SDNS despite cyclophosphamide therapy received chlorambucil, levamisole or another course of cyclophosphamide. The treatment responses were recorded and the mean duration of follow up was 96 months. Seventeen patients (37%) experienced no relapse after cyclophosphamide therapy. Twenty-five patients (54%) had varied responses. Only four patients showed no effect. Children who still had SDNS despite cyclophosphamide therapy received second or more alternative drugs. Cyclophosphamide with or without chlorambucil resolved steroid-dependency in 33 of 46 (72%) children who either had complete remission or developed steroid-sensitive, rather than steroid-dependent, nephrotic syndrome. With the exception of four patients who were lost to follow up and four who were refractory and needed other treatment, most children with SDNS could spare the steroid (complete remission or steroid sensitive nephrotic syndrome) after using one or more of these modulating agents.

Dyspnoea in a young woman with active systemic lupus erythematosus

Diffuse alveolar haemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). We present the case of a 24-year-old Cambodian woman with SLE followed in the Brigham and Women's Hospital Lupus Center in Boston, Massachusetts. She presented with dyspnoea and chest pain and was found to have DAH that required a prolonged hospitalization that was complicated by recurrent DAH episodes and multiple infections. We discuss the diagnostic approach and management of patients with SLE-associated DAH as well as treatment options for refractory disease. Emerging therapies include plasmapheresis, the anti-CD20 monoclonal antibody rituximab and recombinant activated Factor VII therapy. In addition, we review the literature to date and compile what is known about the epidemiology, presenting features, diagnostic findings, management and outcomes in this condition. We found that DAH has been reported in 1.9% of patients with SLE. These patients were mostly female (88%) and young (mean age 30.2 years). Common presenting features included dyspnoea (94%), anaemia (97%) and new radiographic chest infiltrate (99%). Bronchoscopy, when performed, identified DAH in 90% of cases. Corticosteroids were the mainstay of care, and usage of cyclophosphamide varied by report. Despite recent advances in therapy, mortality has not improved substantially (48% overall survival versus 53% survival in reports published since 1993).

Intravenous cyclophosphamide is the drug of choice for steroid dependent nephrotic syndrome.

Steroid dependency is a major problem seen after therapy for idiopathic nephrotic syndrome in childhood. Although there is consensus about the usage of cyclophosphamide (CYC) in frequent relapsers, there is still a controversy concerning its usage in steroid-dependent nephrotic syndrome (SDNS). In the present study, nineteen children with SDNS were treated with CYC: ten via the intravenous (i.v.) route, and nine via the oral route. Remission was then maintained with prednisolone. Oral CYC therapy consisted of CYC at a dose of 2 mg/kg per day for 12 weeks. Intravenous (i.v.) CYC therapy consisted of CYC 500 mg/m2 per month (with intravenous 3500 cc/m2 per 24 h one-third saline hydration) for 6 months. The cumulative dose of CYC was 168 mg/kg in the oral group and 132 mg/kg in the IV group. Daily oral CYC dose was 1.96~0.31 mg/kg, whereas i.v. CYC dose was 0.73~0.03 mg/kg. Long-term complications and side-effects such as alopecia, infection and hemorrhagic cystitis were not observed in the i.v. CYC treated group. In the long term, the dosage of prednisolone that held remission after CYC, the annualized relapse rates and the subsequent relapse time were significantly better in the i.v. CYC group, and the number of patients in remission for 2 years was significantly higher in the i.v. treated group (P<0.05). In SDNS, i.v. CYC has a long lasting effect with lower annualized relapse rates and longer subsequent relapse time with a lower steroid dosage required to maintain remission than oral CYC. The results of the present study showed the safety of the i.v. route, and it is the preferable treatment in noncompliant patients for its long lasting remission and simple and inexpensive follow up.