Experience with levamisole in frequently relapsing, steroid-dependent nephrotic syndrome

This was a controlled prospective study on the use of an immunomodulator drug, levamisole, in the treatment of frequently relapsing, steroid-dependent (FR/SD) idiopathic nephrotic syndrome. The study was started on 1 January 2001 and completed on 31 December 2003. There were two groups: a treatment group who received levamisole (2.5 mg/kg) on alternate days for 1 year and a control group who received low-dose prednisolone only (<0.5 mg/kg) on alternate days for 1 year. There were a total of 56 patients (32 in the treatment group and 24 in the control group). The male to female ratio was 1.66:1 in both groups. The mean age upon initial diagnosis was 3.3 years in the levamisole group versus 4.3 years in the control group. The mean duration from diagnosis to the start of the second line treatment was 3.2 years in the levamisole group versus 2.8 years in the control group. The relapse rate and the total cumulative dose of prednisolone during the year prior to second line therapy was compared to that during the year following the institution of second line therapy in 56 patients. The mean relapse rate was reduced more significantly in the levamisole group. It was reduced by 0.29 versus 0.11 relapses/patient/month in the control group (P =0.0001). The mean cumulative dose of steroids was also reduced more significantly in the levamisole group. It was reduced by 293 versus 102 mg/m²/month in the control group (P <0.0001). Therapy failure was seen in 3/32 (9.4%) in the levamisole group versus 12/24 (50%) in the control group. Of the patients, 20/32 (62.5%) using levamisole were relapse-free in the follow-up year post therapy, while no patient was relapse-free in the control group over the same period. No major adverse effects of levamisole were seen. The cost of levamisole therapy was estimated to be US$ 25 per year for a 20-kg body weight child. Thus, we concluded that levamisole is a highly efficacious, safe and easily affordable initial therapy for FR/SD idiopathic nephrotic syndrome.     

A double-blind pediatric evaluation of levamisole in the prevention of recurrent upper respiratory tract infections

Levamisole was tested double-blind in 106 children with recurrent upper respiratory tract infections. They received either levamisole (n=53) or placebo (n=53) 0.5 ml/kg bodyweight b.i.d. for two consecutive days each week for six months. A control examination was performed every two months. Both groups were compared by means of the Fisher-test and the Mann-Whitney U-test (two-tailed probability each). Improvement was observed more frequently in the levamisole group with regard to the number of episodes of infection, and the total duration and severity of the infections. No side-effects, except for some stomach complaints in one levamisole patient, were reported.     

Haematological and serum biochemical profiles of buffalo heifers as influenced by levamisole

Serum was separated from blood samples of six healthy buffalo heifers (1–1.5 years) on day 0 (control) and after 1, 7 and 14 days of levamisole (15 mg/kg body weight) administered orally. Significant differences were observed among monocytes, ESR (1 h) and of percentage PCV (Packed Cell Volume) after 1 and 7 days of levamisole administration. Mean corpuscular volume (MCV) and mean corpuscular haemoglobin concentration (MCHC) were significantly different. Significant changes were observed among total serum protein, albumin and globulin concentrations after 1 and 7 days of levamisole administration. A significant increase in serum urea concentration was observed on day 14 of the experiment.Abbreviations >DLC differential leucocyte count - >ESR erythrocyte sedimentation rate - >HB Haemoglobin - >MCH mean corpuscular haemoglobin - >MCV mean corpuscular volume - >MCHC mean corpuscular haemoglobin concentration - >PCV packed cell volume - >RBC red blood cell - >TLC total lymphocyte count - >WBC white blood cell     

Effects of oral administration of levamisole on non-specific immunity, serum proteins and health in normal colostrum-fed neonatal dairy calves

Soon after levamisole became widely used as a veterinary anthelmintic, it was recognised that concurrent enhancement of immune responsiveness sometimes accompanied anthelmintic treatment, especially in old or chronically ill animals. There are many reports concerning the immunomodulatory effects of levamisole in immunocompromised and vaccinated animals, but information about the effects of levamisole in immunocompetent animals is limited and controversial. Thirty Holstein dairy calves were randomly divided into two groups: test (n=15) and control (n=15). Blood samples were taken from the jugular vein, between 24 h and 48 h after birth, and put into EDTA-containing tubes and plain tubes; levamisole was then administrated orally at a dose of 2 mg/kg body weight three times at 1-day intervals in test groups. Blood sampling from all the calves was continued at days 7, 14, 21 and 28. The weight of calves was measured only at days 1 and 28 (before feeding). The levels of packed cell volume (PCV) (microhaematocrit), total white blood cells (WBCS) and differential leukocyte count (manual standard methods), total serum protein (colorimetry), beta and gamma globulins (electrophoresis), albumin:globulin (A:G) (calculated) and disease occurrence were measured and recorded. Appropriate statistical methods were used for data analysis, and P0.05 was considered as significant. No significant differences were seen for PCV, total serum protein, WBC count and health between groups. In the test group, neutrophil level at day 14 and monocyte level at day 21 were significantly higher than in the control group (P<0.05). Electrophoresis showed no significant differences for beta globulin level and A:G between groups, but gamma globulin level at day 28 was significantly higher in the test group (P<0.05).     

Autoimmune thyroiditis in a child with steroid-dependent nephrotic syndrome

Autoimmune thyroiditis is rarely described in association with nephrotic syndrome. Herein we report a girl who developed autoimmune thyroiditis insidiously during the course of minimal change nephrotic syndrome. She was streroid-sensitive, but developed severe steroid dependency and did not respond to cyclophosphamide therapy. She went into stable remission with levamisole. Five months after introduction of levamisole a mild goiter was found on systematic examination at school. The diagnosis of autoimmune thyroiditis was established with typical ultrasound appearance of the thyroid gland along with significant titers of antithyroid antibodies. It is very unlikely that levamisole was responsible for thyroiditis because experimental animal administration of high doses of levamisole inhibited lymphocyte infiltration of the thyroid. Since levamisole has had a beneficial effect on the nephrotic syndrome in our patient we decided to continue the treatment. She has been receiving levamisole for 3 years, and no adverse effects have been observed during the treatment period.     

Alkaline phosphatase inhibition by levamisole prevents 1,25-dihydroxyvitamin D3-stimulated bone mineralization in the mouse

Summary To determine the relationship between alkaline phosphatase (AP), 1,25(OD)₂D₃ and bone formationin vivo, we have examined the effects of levamisole, a stereospecific inhibitor of AP on bone formation and on 1,25(OH)₂D₃-stimulated bone mineralization in the mouse. Normal mice were injected daily with levamisole at doses of 40 and 80 mg/kg/b.w. The compound was given alone or in combination with 1,25(OH)₂D₃ infusion (0.05 μg/kg/d) for 7 days. Treatment with levamisole alone inhibited the serum AP activity (mainly of skeletal origin in mice) by 18.4 and 61.3% for the low and high dose respectively. No deleterious effect on body growth, tibia length, and bone cells population was detected. The moderate inhibition of AP activity produced by the lower dose of levamisole alone (18.4%) or in combination with 1,25(OH)₂D₃ (37.9%) was associated with a reduced endosteal matrix apposition rate (MaAR) determined by double³H-proline labeling method. This effect was related to a levamisole-induced fall in serum phosphate. Despite the moderate inhibition of AP activity, the mineral apposition rate (MiAR) determined by the double tetracycline labeling method remained normal. Moreover, 1,25(OH)₂D₃ infusion still resulted in increased MiAR which was stimulated to the same extent as in the absence of levamisole. By contrast, the more severe inhibition of AP activity induced by 80 mg/kg of levamisole alone (61.3%) or in combination with 1,25(OH)₂D₃ (45.8%) inhibited both the MaAR and the MiAR and prevented the stimulatory effect of 1,25(OH)₂D₃ on bone mineralization. The data show that AP activity affects the bone matrix and mineral apposition ratesin vivo and that severe inhibition of AP activity inhibits the 1,25(OH)₂D₃-induced stimulation of bone mineralization in the mouse.     

盐酸左旋咪唑片的右旋体监测

分别采用手性高效液相色谱法和旋光法检查和控制盐酸左旋咪唑片中右旋异构体的含量.方法一:使用Chiral AGP手性柱,10 mmol·L-1甲酸铵溶液(pH值约6.2)为流动相,检测波长为214 nm,盐酸左旋咪唑与对映体的分离度大于1.5.方法二:使用二氯甲烷提取后测定旋光度,可有效消除辅料的干扰.两种方法均可用于盐酸左旋咪唑片中的右旋体杂质的控制.     

Levamisole suppresses activation and proliferation of human T cells by the induction of a p53-dependent DNA damage response

Levamisole (LMS) is a small molecule used in the treatment of idiopathic nephrotic syndrome (INS). The pathogenesis of INS remains unknown, but evidence points toward an immunological basis of the disease. Recently, LMS has been shown to increase the relapse-free survival in INS patients. While LMS has been hypothesized to exert an immunomodulatory effect, its mechanism of action remains unknown. Here, we show that LMS decreased activation and proliferation of human T cells. T-cell activation-associated cytokines such as IL-2, TNF-α, and IFN-γ were reduced upon LMS treatment, whereas IL-4 and IL-13 were increased. Gene expression profiling confirmed that the suppressive effects of LMS as genes involved in cell cycle progression were downregulated. Furthermore, genes associated with p53 activation were upregulated by LMS. In agreement, LMS treatment resulted in p53 phosphorylation and increased expression of the p53 target gene FAS. Accordingly, LMS sensitized activated T cells for Fas-mediated apoptosis. LMS treatment resulted in a mid-S phase cell cycle arrest accompanied by γH2AX-foci formation and phosphorylation of CHK1. Our findings indicate that LMS acts as an immunosuppressive drug that directly affects the activation and proliferation of human T cells by induction of DNA damage and the activation of a p53-dependent DNA damage response.     

Susac-Like Syndrome in a Chronic Cocaine Abuser: Could Levamisole Play a Role?

Introduction

Toxic leukoencephalopathy is a possible but rare complication of chronic cocaine abuse. The role of adulterants, mainly levamisole, is still debated.

Case Report

We describe an atypical case of fatal leukoencephalopathy mimicking Susac syndrome in a 22-year-old man who was chronically abusing cannabis and cocaine. Exposure to levamisole as adulterant to cocaine was proven by hair analysis. Despite cessation of exposure to cocaine and aggressive immunosuppressive therapy, the patient remained in a minimally conscious state until death.

Discussion

Susac syndrome is a rare entity, and its etiology is not yet fully elucidated. The toxic etiologies have been poorly investigated to date. Further observations are required to determine if cocaine and/or adulterants might play a significant role.     

Levamisole‐induced occlusive necrotising vasculitis in cocaine abusers: an unusual cause of skin necrosis and neutropenia

We present three cases describing the various skin manifestations of presumed levamisole‐contaminated cocaine use. Antibody‐mediated vasculitis and neutropenia were consistent findings in these cases and repeat exposure resulted in distinct dermatologic complications. This phenomenon of levamisole‐induced vasculitis and neutropenia is being increasingly described and has characteristic wound manifestations that must be recognised and treated early.