Rhamnosidase activity of selected probiotics and their ability to hydrolyse flavonoid rhamnoglucosides.

Bioavailability of flavonoids is low, especially when occurring as rhamnoglucosides. Thus, the hydrolysis of rutin, hesperidin, naringin and a mixture of narcissin and rutin (from Cyrtosperma johnstonii) by 14 selected probiotics was tested. All strains showed rhamnosidase activity as shown using 4-nitrophenyl α-L-rhamnopyranoside as a substrate. Hesperidin was hydrolysed by 8-27% after 4 and up to 80% after 10 days and narcissin to 14-56% after 4 and 25-97% after 10 days. Rutin was hardly hydrolysed with a conversion rate ranging from 0 to 5% after 10 days. In the presence of narcissin, the hydrolysis of rutin was increased indicating that narcissin acts as an inducer. The rhamnosidase activity as well as the ability to hydrolyse flavonoid rhamnoglucosides was highly strain specific. Naringin was not hydrolysed by rhamnosidase from probiotics, not even by the purified recombinant enzyme, only by fungal rhamnosidase. In conclusion, rhamnosidases from the tested probiotics are substrate specific cleaving hesperidin, narcissin and to a small extent rutin, but not naringin.

Antioxidant activity and cytotoxicity of Cyrtosperma johnstonii extracts on drug sensitive and resistant leukemia and small cell lung carcinoma cells.

CONTEXT: The number of patients with cancer is increasing. New therapeutic agents to overcome drug-resistant tumors are urgently needed. Cyrtosperma johnstonii N.E. Br. (Araceae) is used for treatment of cancer in Thai traditional medicine. This study aimed to evaluate antioxidant activity and cytotoxicity of C. johnstonii extracts on human cancer cells. MATERIALS AND METHODS: Dried powder of C. johnstonii rhizomes was extracted with several solvents. The 0.1 mg/ml extract solution was tested for antioxidant activity by 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and ferric reducing antioxidant power (FRAP) assays. Color formation from 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to determine cell viability. Standardization of the extract was performed by high-performance liquid chromatography (HPLC) with photodiode array detector at 254 and 360 nm. Cell cycle arrest was evaluated by flow cytometry after 5 min, 12 h and 24 h treated with 20 µg/ml of the acetone extract. RESULTS: The acetone extract exhibited the highest phenolic content and antioxidant activity (TEAC and EC values = 19.2 ± 0.14 and 19.2 ± 0.31 mM/mg, respectively). The IC50 values for leukemia ranged from 11 ± 1 to 29 ± 3 µg/ml and from 5 ± 2 to 6 ± 0 µg/ml for small cell lung carcinoma cells. Cell cycle arrest occurred at the G2/M phase followed by apoptosis. HPLC analysis revealed that rutin is the major constituents of the extract. DISCUSSION AND CONCLUSION: The acetone extract of C. johnstoni is a promising source of natural antioxidants and anticancer. The extract inhibits cancer cells effectively with less effect on normal cells.

Stereotactic Radiosurgery for Benign Cavernous Sinus Meningiomas: A Multicentre Study and Review of the Literature.

Cavernous sinus meningiomas (CSMs) remain a surgical challenge due to the intimate involvement of their contained nerves and blood vessels. Stereotactic radiosurgery (SRS) is a safe and effective minimally invasive alternative for the treatment of small- to medium-sized CSMs. Objective: To assess the medium- to long-term outcomes of SRS for CSMs with respect to tumour growth, prevention of further neurological deterioration and improvement of existing neurological deficits. This multicentric study included data from 15 European institutions. We performed a retrospective observational analysis of 1222 consecutive patients harbouring 1272 benign CSMs. All were treated with Gamma Knife stereotactic radiosurgery (SRS). Clinical and imaging data were retrieved from each centre and entered into a common database. All tumours with imaging follow-up of less than 24 months were excluded. Detailed results from 945 meningiomas (86%) were then analysed. Clinical neurological outcomes were available for 1042 patients (85%). Median imaging follow-up was 67 months (mean 73.4, range 24-233). Median tumour volume was 6.2 cc (+/-7), and the median marginal dose was 14 Gy (+/-3). The post-treatment tumour volume decreased in 549 (58.1%), remained stable in 336 (35.6%) and increased in only 60 lesions (6.3%), yielding a local tumour control rate of 93.7%. Only 27 (2.8%) of the 60 enlarging tumours required further treatment. Five- and ten-year actuarial progression-free survival (PFS) rates were 96.7% and 90.1%, respectively. Tumour control rates were higher for women than men (p = 0.0031), and also for solitary sporadic meningiomas (p = 0.0201). There was no statistically significant difference in outcome for imaging-defined meningiomas when compared with histologically proven WHO Grade-I meningiomas (p = 0.1212). Median clinical follow up was 61 months (mean 64, range 6-233). Permanent morbidity occurred in 5.9% of cases at last follow-up. Stereotactic radiosurgery is a safe and effective method for treating benign CSM in the medium term to long term.

Randomized, double-blind, placebo-controlled study of oral lactobacilli to improve the vaginal flora of postmenopausal women.

OBJECTIVE: The purpose of this randomized, double-blind, placebo-controlled study was to evaluate the influence of the orally administered probiotic strains Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 on the quality of the vaginal flora in postmenopausal women. STUDY DESIGN: Postmenopausal women with Nugent scores between 4 and 6 in initial vaginal swab, were randomized into two groups. Women in the intervention group received probiotic capsules containing 2.5x10(9)CFU (colony forming units) each of lyophilized L. rhamnosus GR-1 and L. reuteri RC-14 and women in the control group received an oral placebo once daily, in both groups for 14 days. Final vaginal swabs were taken 1 day after the last administration of the medication. The primary efficacy variable was a change in the Nugent score between baseline and the end of the study of at least two grades in each individual patient. RESULTS: Seventy two women were recruited in the study, 35 assigned to the intervention group and 37 to the control group. Twenty-one of the 35 subjects (60%) in the intervention group and 6 of the 37 subjects (16%) in the control group showed a reduction in the Nugent score by at least two grades. The difference in the number of patients with improvement was highly significant (p=0.0001). The median difference in Nugent scores between baseline and the end of the study was 3 in the intervention group and 0 in the control group (p=0.0001). CONCLUSION: Our results provide evidence for an alternative modality to restore the normal vaginal flora using specific probiotic strains administered orally.

Selection of reliable reference genes for qPCR studies on chondroprotective action.

BACKGROUND: Chondroprotective agents (CPA) such as glucosamine, curcumin and diacerein represent potential remedies for the management of osteoarthritis and several studies have been performed on their effects in-vitro and in-vivo. For the investigation of chondroprotective action on chondrocyte gene expression, quantitative real-time RT-PCR is the method of choice. However, validation of applied normalization strategies represents a crucial and sometimes neglected step in the analysis process. Therefore, the present study aimed to determine the expression stability of common reference genes (ACTB, Beta actin; GAPDH, Glyceraldehyde-3-phosphate; B2M, Beta-2-microglobulin; HPRT1, Hypoxanthine phosphoribosyl-transferase I; SDHA, Succinate dehydrogenase complex, subunit A; YWHAZ, Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide) under the influence of glucosamine, curcumin and diacerein in the IL-1beta-stimulated C-28/I2 chondrocyte model, using the geNorm software tool. RESULTS: CPA treatment of C-28/I2 chondrocytes significantly affected the expression level of many reference genes (p < 0.05). According to their expression stability, geNorm analysis revealed rankings of the 3 most stable genes (from most stable to least stable) as follows: GAPDH, B2M and SDHA in glucosamine treated samples and HPRT1, GAPDH and B2M in curcumin or diacerein treated samples. Interestingly, ACTB was one of the most variably expressed genes throughout all experiments. CONCLUSION: Our study points out the problem of relying on commonly used reference genes without an accurate validation process. For normalization purposes in gene profiling studies on glucosamine action, the genes GAPDH, B2M and SDHA are recommended as single reference genes depending on the expression level of the target gene or more favourably in combination. For experiments with curcumin and diacerein the use of HPRT1, GAPDH and B2M should be considered.

Prebiotic potential of neutral oligo- and polysaccharides from seed mucilage of Hyptis suaveolens.

Prebiotics are selectively fermented by the gastrointestinal microflora, resulting in benefits to human health. The seed mucilage of Hyptis suaveolens contains neutral and acidic polysaccharides in a ratio of 1:1. The neutral polysaccharides consist of galactose, glucose and mannose whereas the acidic polysaccharides contain fucose, xylose and 4-O-methylglucuronic acid -residues. The growth of probiotics in the presence of total, acidic or neutral polysaccharides and oligosaccharides was tested using turbidity measurements. The majority (11 out of 14) of the tested probiotic strains significantly grew in the neutral fraction. Growth occurred with some time delay, but may be longer lasting than with other lower molecular prebiotics. The extent of growth increased with neutral polysaccharides from H. suaveolens corresponding to the externally available galactose units (20%). In conclusion, neutral poly- and oligosaccharides from H. suaveolens have a prebiotic potential characterized by a delayed but long lasting effect.

Molecular dimensions and structural features of neutral polysaccharides from the seed mucilage of Hyptis suaveolens L.

The seed mucilage of Hyptis suaveolens L. includes acid - and neutral heteropolysaccharides in a ratio of about 1:1. The anionic charged fraction responsible for swelling and viscous behaviour possesses an average molar mass of Mw=350kg/mol, Mn=255kg/mol. The neutral polysaccharide fraction shows an average molar mass of Mw=47kg/mol and Mn=28kg/mol and is composed of d-Galp-, d-Glcp- and d-Manp residues in a molar ratio of about 3:2:1. The structural features present galactoglucan (30%) and galactoglucomannan (70%) with a high level of terminal ß-linked d-Galp residues (18%). Structural details of galactoglucomannan are derived by combined enzymatic and chemical methods as well as NMR spectroscopy. Sequences of octa/nonasaccharide ß-d-Glcp-(1→4)[ß-d-Galp-(1→2)-α-d-Galp-(1→6)]-ß-d-Manp-(1→4)-ß-d-Glcp-(1→4)-ß-d-Glcp-(1→4)[ß-d-Galp-(1→2)-α-d-Galp-(1→6)]-ß-d-Manp and lower mass tetrasaccharide repeating units ß-d-Glcp-(1→4)[ß-d-Galp-(1→2)-α-d-Galp-(1→6)]-ß-d-Manp were found. The level of the prebiotic activity is related to the availability of ß-linked d-Galp residues in the side chains of the molecules.

Compounds from Caesalpinia sappan with anti-inflammatory properties in macrophages and chondrocytes.

The heartwood of Caesalpinia sappan is a traditional ingredient of food and beverages in South East Asia and has been used in traditional medicine as an analgesic and anti-inflammatory drug or to promote blood circulation. Scientific studies have confirmed different bioactivities associated with its use. Here, five fractions were isolated from the ethanolic extract of C. sappan heartwood, including episappanol (1), protosappanin C (2), brazilin (3), (iso-)protosappanin B (4) and sappanol (5) using high-performance liquid chromatography (HPLC). All compounds were tested for their anti-inflammatory effects in two different cell lines. Cytokine concentrations in the cell supernatant were determined using enzyme-linked immunosorbent assay (ELISA), and mRNA levels were measured using reverse-transcription quantitative polymerase chain reaction (RT-qPCR). In lipopolysaccharide-stimulated macrophages, all compounds significantly inhibited the secretion of the pro-inflammatory cytokines interleukin (IL-6) and tumor necrosis factor-alpha (TNF-α). Sappanol (5) increased the secretion of the anti-inflammatory IL-10. In IL-1ß-stimulated chondrocytes, all fractions reduced the mRNA expression and the secretion of the pro-inflammatory cytokines IL-6 and TNF-α. The highest anti-inflammatory effect was found for brazilin (3) in both cell lines. Of note, this is the first study which shows the anti-inflammatory effect of sappanol and episappanol. This study provides evidence for the efficacy of the traditional use of C. sappan as an anti-inflammatory remedy. Given the high prevalence of inflammation-related pathologies including arthritis, and the urgent need to clinically intervene with these diseases, the anti-inflammatory activity of diverse compounds from C. sappan may be of interest for the development of complementary and alternative treatment strategies.

Anti-inflammatory Effects of Compounds from Polygonum odoratum.

Polygonum odoratum is an edible plant traditionally used as an antidiabetic, antimicrobial, anti-inflammatory, and antitumor agent in Asia. The aim of the study was to evaluate the anti-inflammatory effect of P. odoratum and the isolation and characterization of its main fractions. Extracts of the aerial parts were tested for anti-inflammatory activity as indicated by a change in the cytokine secretion in lipopolysaccharide-stimulated macrophages. After separation of the extract by reversed-phase high-performance liquid chromatography, the anti-inflammatory activity of the fractions was determined. Furthermore, the two main fractions were identified by nuclear magnetic resonance spectroscopy ((1)H- and (13)C-NMR). The ethanolic extract significantly reduced IL-6 secretion (IC50 25 pg/mL). The two main fractions (5 and 7) significantly decreased IL-6 production with an IC(50) of 102 µM (5) and 77 µM (7), respectively, and were identified as scutellarein-7-glucoside (5) and quercitrin (7). Since inflammation plays a major role in various diseases with high prevalence globally, it may be of importance that P. odoratum and its main constituents scutellarein-7-glucoside and quercitrin can be used as either an alternative or complementary treatment. Additionally, both are glycosides and their activity may be enhanced tremendously by deglycosylation by the gut microbiota.

Apoptosis of human breast cancer cells induced by microencapsulated betulinic acid from sour jujube fruits through the mitochondria transduction pathway.

Betulinic acid (BA), a natural pentacyclic triterpenoid, was isolated from sour jujube fruits for the first time. An inclusion complex comprising BA and ß-cyclodextrin (ß-CD) was formed to improve the dissolution of BA, but little is known about its anticancer effect. In this study, the anti-proliferative and apoptosis mechanisms of BA-ß-CD on human breast cancer MCF-7 cells were further investigated. Experimental results confirmed that the complexation model inhibited the growth of MCF-7 cells in a dose-dependent manner, arrested cell cycle in the G2/M phase and induced apoptosis via the mitochondria transduction pathway. Gene and protein analyses showed that the complexation model significantly inhibited Bcl-2 expression and promoted Bax expression, causing caspase-3 and caspase-9 cascade activation. These findings corroborated evidence on microencapsulated BA as an apoptosis inducer in MCF-7 cells. Thus, sour jujube fruits may have potential use as a breast cancer chemotherapeutic agent.

Azido derivatives of cellobiose: oxidation at C1 with cellobiose dehydrogenase from Sclerotium rolfsii.

We report the chemo-enzymatic synthesis of three cellobiono-1,5-lactone azido derivatives, designed as building blocks for biomedical polymer scaffolds. The synthesis is based on regioselective protection of cellobiose or 1,6-O-anhydro-ß-d-cellobiose before azidation and subsequent deprotection. The oxidation to the corresponding cellobiono-1,5-lactones was investigated with 6'-azido-6'-deoxycellobiose (6'N3Clb, 5), 6-azido-6-deoxycellobiose (6N3Clb, 11) and 2-azido-2-deoxycellobiose (2N3Clb, 15) under the catalysis of cellobiose dehydrogenase (CDH) from the plant-pathogenic fungus Sclerotium rolfsii. Substrate binding characteristics and kinetics of CDH for the three cellobiose azido derivatives were studied employing computational docking, steady-state and presteady-state techniques. The process of enzymatic oxidation of the cellobiose azido intermediates was optimized by using the available kinetic information. Whereas the conversion of 15 by CDH is very slow, the conversion of 5 and 11 by a regenerated, bi-enzymatic process (CDH/redox mediator/laccase/O2) is fast, quantitative and produces azido derivatives of cellobiono-1,5-lactone in an environmentally friendly, oxygen-driven process.

Caesalpinia sappan extract inhibits IL1ß-mediated overexpression of matrix metalloproteinases in human chondrocytes.

Exacerbated production of matrix metalloproteinases (MMPs) is a key event in the progression of osteoarthritis (OA) and represents a promising target for the management of OA with nutraceuticals. In this study, we sought to determine the MMP-inhibitory activity of an ethanolic Caesalpinia sappan extract (CSE) in human OA chondrocytes. Thus, human articular chondrocytes isolated from OA cartilage and SW1353 chondrocytes were stimulated with Interleukin-1beta (IL1ß), without or with pretreatment with CSE. Following viability assays, the production of MMP-2 and MMP-13 was assessed using ELISA, whereas mRNA levels of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-13 and TIMP-1, TIMP-2, TIMP-3 were quantified using RT-qPCR assays. Chondrocytes were co-transfected with a MMP-13 luciferase reporter construct and NF-kB p50 and p65 expression vectors in the presence or absence of CSE. In addition, the direct effect of CSE on the proteolytic activities of MMP-2 was evaluated using gelatin zymography. We found that CSE significantly suppressed IL1ß-mediated upregulation of MMP-13 mRNA and protein levels via abrogation of the NF-kB(p65/p50)-driven MMP-13 promoter activation. We further observed that the levels of IL1ß-induced MMP-1, MMP-3, MMP-7, and MMP-9 mRNA, but not TIMP mRNA levels, were down-regulated in chondrocytes in response to CSE. Zymographic results suggested that CSE did not directly interfere with the proteolytic activity of MMP-2. In summary, this study provides evidence for the MMP-inhibitory potential of CSE or CSE-derived compounds in human OA chondrocytes. The data indicate that the mechanism of this inhibition might, at least in part, involve targeting of NF-kB-mediated promoter activation.

Quantification of butyryl CoA:acetate CoA-transferase genes reveals different butyrate production capacity in individuals according to diet and age.

The gastrointestinal microbiota produces short-chain fatty acids, especially butyrate, which affect colonic health, immune function and epigenetic regulation. To assess the effects of nutrition and aging on the production of butyrate, the butyryl-CoA:acetate CoA-transferase gene and population shifts of Clostridium clusters lV and XlVa, the main butyrate producers, were analysed. Faecal samples of young healthy omnivores (24 ± 2.5 years), vegetarians (26 ± 5 years) and elderly (86 ± 8 years) omnivores were evaluated. Diet and lifestyle were assessed in questionnaire-based interviews. The elderly had significantly fewer copies of the butyryl-CoA:acetate CoA-transferase gene than young omnivores (P=0.014), while vegetarians showed the highest number of copies (P=0.048). The thermal denaturation of the butyryl-CoA:acetate CoA-transferase gene variant melting curve related to Roseburia/Eubacterium rectale spp. was significantly more variable in the vegetarians than in the elderly. The Clostridium cluster XIVa was more abundant in vegetarians (P=0.049) and in omnivores (P<0.01) than in the elderly group. Gastrointestinal microbiota of the elderly is characterized by decreased butyrate production capacity, reflecting increased risk of degenerative diseases. These results suggest that the butyryl-CoA:acetate CoA-transferase gene is a valuable marker for gastrointestinal microbiota function.

Anti-inflammatory activity of an ethanolic Caesalpinia sappan extract in human chondrocytes and macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia sappan is a common remedy in Traditional Chinese Medicine and possesses diverse biological activities including anti-inflammatory properties. Osteoarthritis (OA) is a degenerative joint disease with an inflammatory component that drives the degradation of cartilage extracellular matrix. In order to provide a scientific basis for the applicability of Caesalpinia sappan in arthritic diseases, the present study aimed to assess the effects of an ethanolic Caesalpinia sappan extract (CSE) on human chondrocytes and macrophages. MATERIALS AND METHODS: Primary human chondrocytes were isolated from cartilage specimens of OA patients. Primary cells, SW1353 chondrocytes and THP-1 macrophages were serum-starved and pretreated with different concentrations of CSE prior to stimulation with 10 ng/ml of interleukin-1beta (IL-1ß) or lipopolysaccharide (LPS). Following viability tests, nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) were evaluated by Griess assay and ELISA, respectively. Using validated real-time PCR assays, mRNA levels of IL-1ß, TNF-α, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were quantified. SW1353 cells were cotransfected with a COX-2 luciferase reporter plasmid and nuclear factor-kappa-B (NF-κB) p50 and p65 expression vectors in the presence or absence of CSE. RESULTS: CSE dose-dependently inhibited the expression of pro-inflammatory cytokines IL-1ß and TNF-α in IL-1ß-stimulated chondrocytes and LPS-stimulated THP-1 macrophages. CSE further suppressed the synthesis of NO in primary OA chondrocytes by blocking iNOS mRNA expression. The inhibition of COX-2 transcription was found to be related with the CSE inhibition of the p65/p50-driven transactivation of the COX-2 promoter. CONCLUSIONS: The present report is first to demonstrate the anti-inflammatory activity of CSE in an in vitro cell model of joint inflammation. CSE can effectively abrogate the IL-1ß-induced over-expression of inflammatory mediators at the transcriptional level in human chondrocytes and macrophages, most likely by inhibiting NF-κB (p65/p50) signaling. Blockade of IL-1ß-induced NF-κB signaling and its downstream pro-inflammatory targets by CSE may be beneficial for reducing cartilage breakdown in arthritis.

IL-1beta and TNF-alpha alter the glycophenotype of primary human chondrocytes in vitro.

Despite the significance of glycoproteins for extracellular matrix assembly in cartilage tissue, little is known about the regulation of the chondrocyte glycophenotype under inflammatory conditions. The present study aimed to assess the effect of IL-1beta and TNF-alpha on specific features of the glycophenotype of primary human chondrocytes in vitro. Using LC-MS, we found that both cytokines increased overall sialylation of N- and O-glycans and induced a shift towards alpha-(2-->3)-linked sialic acid residues in chondrocyte glycoproteins. These results were supported by quantitative PCR showing increased expression of alpha-(2-->3) sialyltransferases in treated cells. Moreover, we found that both IL-1beta and TNF-alpha induced a considerable shift from oligomannosidic glycans towards complex-type N-glycans. In contrast, core alpha-(1-->6)-fucosylation of chondrocyte N-glycans was found to be reduced particularly by TNF-alpha. In summary, inflammatory conditions induce specific alterations of the chondrocyte glycophenotype which might affect cell-matrix interactions or the function of endogenous lectins.

European position paper on endoscopic management of tumours of the nose, paranasal sinuses and skull base.

Tumours affecting the nose, paranasal sinuses and adjacent skull base are fortunately rare. However, they pose significant problems of management due their late presentation and juxtaposition to important anatomical structures such eye and brain. The increasing application of endonasal endoscopic techniques to their excision offers potentially similar scales of resection but with reduced morbidity. The present document is intended to be a state-of-the art review for any specialist with an interest in this area 1. to update their knowledge of neoplasia affecting the nose, paranasal sinuses and adjacent skull base; 2. to provide an evidence-based review of the diagnostic methods; 3. to provide an evidence-based review of endoscopic techniques in the context of other available treatments; 4. to propose algorithms for the management of the disease; 5. to propose guidance for outcome measurements for research and encourage prospective collection of data. The importance of a multidisciplinary approach, adherence to oncologic principles with intent to cure and need for long-term follow-up is emphasised.

Efficacy and safety of radiosurgical callosotomy: a retrospective analysis.

PURPOSE: Anterior callosotomy is a surgical option for the treatment of generalized tonic or atonic seizures associated with drop attacks. Besides open surgery, a radiosurgical callosal disconnection using the gamma knife (GK) also can be performed, but reliable data about tolerability and efficacy are sparse. METHODS: Eight patients (three female, five male age range, 5 to 69 years) with severe generalized epilepsy associated with disabling drop attacks underwent GK callosotomy between 1993 and 2004. In six patients, the anterior third of the corpus callosum was radiosurgically disconnected. In one patient a second procedure with GK treatment of the middle third of the corpus callosum was added 17 months later. In two patients posterior GK callosotomy had followed partial hemispherotomy. RESULTS: Drop attacks (DAs) were completely abolished in three patients, and two patients had a marked DA seizure reduction of 60%. Two of four patients with additional generalized tonic-clonic seizures showed a reduction of 100%, and the remaining, a 50% and 60% decrease, respectively. Other seizure types responded less well to the radiosurgical treatment. In both patients with posterior GK callosotomy after hemispherotomy, partial seizures decreased. Beside transient headache in two patients, no immediate or long-term postradiosurgical side effects were observed. CONCLUSIONS: Palliative radiosurgical callosotomy is an efficient and safe noninvasive alternative to the open procedure with comparable results. No signs of postradiosurgical side effects were noted within an up to 12-year posttreatment period.