Disease relevance of SRL

• Intradermal administration of a killed Mycobacterium vaccae suspension (SRL 172) is associated with improvement in atopic dermatitis in children with moderate-to-severe disease [1].
• CONCLUSION: SRL 172 was associated with an improvement in the severity of the dermatitis in children with moderate-to-severe disease [1].
• Except for an increased incidence of pneumonia among patients receiving full-dose CsA and 3 mg/m2/day SRL, the incidences of opportunistic infections were similar in all treatment groups [2].
• Adverse effects attributable to CsA, including hypertension and new-onset diabetes mellitus, were not exacerbated by SRL [2].
• PURPOSE: This phase I-II study was designed to assess safety and clinical efficacy of SRL 172 vaccine in patients with advanced stage IV (AJCC) malignant melanoma [3].

High impact information on SRL

• We propose that this lumenal Ca2+ binding glycoprotein of the sarcoplasmic reticulum be designated "sarcalumenin."[4]
• Patients were randomly treated with corticosteroids (CS); low-dose cyclosporine (CsA) and sirolimus (SRL; group 1; n = 42); or CS, full-dose CsA, and mycophenolate mofetil (group 2; n = 48) [5].
• All of these proteins, calsequestrin, RyR, triadin, SERCAs, and sarcalumenin, are involved in calcium uptake, storage, and release [6].
• Specific lung resistance (SRL) was measured to assess bronchial responses to PAF, and airway responsiveness was determined by deriving a provocative dose of carbachol in breath units causing an increase in SRL to 4 L times centimeters of H2O per liters per second (PD4) from carbachol dose-response curves [7].
• Group I (152) was given sirolimus, mycophenolate mofetil, and prednisone (SRL/MMF/P) between March 2000 and September 2002; group II (168) was given cyclosporine A (CsA)/MMF/P between January 1999 and July 2002; and group III (193) was given azathioprine (AzA)/CsA/P between January 1993 and December 1997 [8].

Chemical compound and disease context of SRL

• Furthermore, CsA potentiated SRL-mediated toxicities, namely myelosuppression and increased cholesterol [9].

Biological context of SRL

• CONCLUSIONS: During a 10-year period marked by changing recipient demographics, the introduction of MMF and SRL did not result in a significant increase in transplant wound-healing complications [8].
• Therefore, we inferred that the oral bioavailability of SRL was low [10].
• SRL trough levels correlated with AUC (r(2) = 0.84, p < 0.001) [11].
• In 11 unsedated sheep, specific lung resistance (SRL) was measured before, immediately after, and serially up to 8 h after inhalation challenge with A. suum antigen [12].
• We postulated that conversion to SRL in renal recipients with KS favored regression of KS lesions without increasing the risk of graft rejection [13].

Anatomical context of SRL

• SRL in lizards can be divided into a dorsomedial portion, which projects ipsilaterally to the spinal cord, and a ventrolateral portion which projects contralaterally [14].
• Possible improved survival of patients with stage IV AJCC melanoma receiving SRL 172 immunotherapy: correlation with induction of increased levels of intracellular interleukin-2 in peripheral blood lymphocytes [3].
• These results show that urate oxidase is important into peroxisomes via a common pathway with acyl-CoA oxidase, and that the C-terminal SRL sequence functions as a peroxisomal-targeting signal [15].
• One external fixation system which has shown particularly good results is a monolateral cross-ankle articulated fixator (Orthofix SRL., Verona, Italy) which allows motion at the ankle joint as the plafond fracture is healing (Figure 1).(ABSTRACT TRUNCATED AT 250 WORDS)[16]
• Salt-depleted rats treated with SRL (0.4-6.4 mg/kg) and/or CsA (2.5-20 mg/kg) were examined for glomerular filtration rates (GFR), lipid levels, and bone marrow cellularity [9].

Associations of SRL with chemical compounds

• The mean values of daily steroid dose and the immunosuppressive drug C0 values were above the putative therapeutic targets: namely, CsA C0=294.9+/-153.2 ng/ml versus 150+/-50 ng/ml and SRL C0=20.1+/-14.0 ng/ml versus 10+/-5 ng/ml, respectively [17].
• With substitution of a lysine residue for arginine in the SRL tripeptide at the C-terminus the import activity was retained [15].
• Three patients developed mild acute cellular rejection 2 wk after initiating SRL therapy, which was fully reversed after prednisolone pulse therapy [18].
• Four immunosuppressive regimens were evaluated as potential risk factors of TMA: cyclosporin + mycophenolate mofetil (CsA + MMF), cyclosporin + sirolimus (CsA + SRL), tacrolimus + myophenolate mofetil (FK + MMF), and tacrolimus + sirolimus (FK + SRL) [19].
• Neither intravenously administered nor aerosolized gallopamil had a significant effect on baseline SRL [12].

Physical interactions of SRL

• The SRL/FKBP complex binds to the protein kinase mTOR [20].

Other interactions of SRL

• SRL 172 increases IL-2 production and the number of NK cells in vivo [21].
• METHODS: Thirty-six liver transplant patients with hepatocellular carcinoma (HCC) who were switched to SRL-based immunosuppression therapy from tacrolimus were enrolled in this study [18].
• Forty-two rugby league players, comprising 21 national league (NRL) and 21 state league (SRL) players, who regularly performed both exercises in their training, served as subjects in this investigation [22].
• RESULTS: Morphonuclear parameters IOD, SURF, LRL, SRL and C were found to correlate with the risk of recurrence and progression of superficial bladder tumours (results for ANOVA respectively IOD P < 0.001; SURF P = 0.02; LRL P = 0.05; RLD P = 0.04; SRL P = 0.04; C P < 0.001) [23].
• Genomic sequences encoding similar proteins containing both the sarcalumenin-like and eps15 homology domains have been identified in humans and Drosophila [24].

Analytical, diagnostic and therapeutic context of SRL

• METHODS: Forty-one children aged 5 to 18 years with moderate-to-severe atopic dermatitis were enrolled in a randomized, double-blind, placebo-controlled trial, where they were given either one intradermal injection of killed Mycobacterium vaccae (SRL 172) or buffer solution (placebo) [1].
• SRL may be used to reduce the exposure of renal allograft recipients to the nephrotoxic effects of CsA [25].
• This method for therapeutic drug monitoring of SRL permits one full-time technician to analyze 100 clinical specimens per week with a 24-h turnaround time [26].
• CONCLUSION: This initial experience suggests that a time-limited and reversible de novo HUS syndrome may be less frequent and milder among renal transplant recipients treated with SRL-based immunosuppression [17].
• RESULTS: The incidence of biopsy-proven acute rejection episodes within the first 6 months after transplant was reduced from 32.0% in the control group to 8.5% in patients receiving SRL (1 or 3 mg/m2/day) and full-dose Sandimmune CsA (P=0.018) [2].

References