Measuring the potency labelling of onabotulinumtoxinA (Botox<Superscript>®</Superscript>) and incobotulinumtoxinA (Xeomin<Superscript>®</Superscript>) in an LD50 assay

The biological potency of botulinum toxin (BT) drugs is determined by a standardised LD50 assay. However, the potency labelling varies vary amongst different BT drugs. One reason for this may be differences in the LD50 assays applied. When five unexpired batches of onabotulinumtoxinA (Botox^®) and incobotulinumtoxinA (Xeomin^®) are compared in the Xeomin^® batch release assay, the potency variability of both BT drugs fell within the range allowed by the European Pharmacopoiea. Statistical analyses failed to detect differences in the potency labelling of both products. Although the existence of a conversion ratio has been questioned recently, our experimental data are in line with previous clinical experience showing that Botox^® and Xeomin^® can be compared using a 1:1 conversion ratio. Identical potency labelling allows easy exchange of both BT drugs in a therapeutic setting, and direct comparison of efficacy, adverse effects and costs.     

Reduced hippocampal neurogenesis in the GR<Superscript>+/−</Superscript> genetic mouse model of depression

Glucocorticoid receptor (GR) heterozygous mice (GR^+/− ) represent a valuable animal model for major depression. GR^+/− mice show a depression-related phenotype characterized by increased learned helplessness on the behavioral level and neuroendocrine alterations with hypothalamo-pituitary-adrenal (HPA) axis overdrive characteristic of depression. Hippocampal brain-derived neurotrophic factor (BDNF) levels have also been shown to be reduced in GR^+/− animals. Because adult hippocampal neurogenesis has been implicated in the pathophysiology of affective disorders, we studied here the effects of the GR^+/− genotype on neurogenesis in vivo. In a 2 × 2 design, GR^+/− mice and GR^+/+ littermate controls were either subjected to 1 h of restraint stress or left undisturbed in their home cages after intraperitoneal injection of BrdU. Stress exposure and BrdU injections were performed once daily for 7 days and neurogenesis analyzed 4 weeks later. BrdU cell counts were significantly reduced as an effect of GR^+/− genotype and as an effect of stress. Majority of the BrdU+ cells showed co-labeling with mature neuronal marker NeuN or astrocytic marker S100β with no further significant effect of either experimental condition or of genotype. In sum, this results in reduced neurogenesis in GR^+/− mice which is further repressed by restraint stress. Our results, thus, reinforce the link between reduced neurogenesis, stress, neurotrophins, and behavioral symptoms of and susceptibility to depression.     

Distribution of Peripherally Injected Peptide YY ([<Superscript>125</Superscript>I] PYY (3–36)) and Pancreatic Polypeptide ([<Superscript>125</Superscript>I] hPP) in the CNS: Enrichment in the Area Postrema

The mechanism by which blood-borne peptide YY (3-36) (PYY(3-36)) and pancreatic polypeptide (PP) inhibit food intake is not clear and could implicate peripheral (vagal afferent pathways) and/or central (direct action on specific brain nuclei) mechanisms. To identify the primary brain structure(s) that could be activated after a peripheral injection of neuropeptide Y-related peptides, we investigated the distribution of radioactive materials using whole body autoradiography and coronal brain sections. Rats were injected with [125I] porcine (p) PYY(3-36) (i.p., 10 microCi) and killed after 30 min, 1, 2, or 4 h. After i.p. administration, significant amounts of radioactive materials were rapidly (<30 min) detected in the blood circulation and various tissues including the kidneys, liver, lung, heart, bone marrow, gastrointestinal tract, and thyroid gland, whereas in the brain, low but significant amounts of radioactive materials were detected at the level of the area postrema. Next, we investigated the distribution of radioactive labeling in the brain after i.v. injections of [125I]pPYY(3-36) (Y2 and Y5 subtypes), [125I] human (h) PP (Y4 and Y5 receptors), and [125I][Leu(31), Pro(34)] pPYY (Y1, Y4 and Y5 classes) in the rat brain. Fifteen minutes post injection, autoradiograms revealed positive signals only in the area postrema after the injection of [125I]-hPP and [125I][Leu(31), Pro(34)]pPYY. Whereas the presence of [125I]pPYY(3-36)-related labeling was detected in the area postrema, subfornical organ, and median eminence. In all other brain structures, including all hypothalamic nuclei and other circumventricular organs, near background level signals were detected. These data suggest that the inhibition of food intake observed after peripheral injections of pPYY(3-36) and hPP could involve receptor activation preferentially located at the level of the area postrema, a structure well-known to be involved in the modulation of food intake.     

<Superscript>123</Superscript>I-β-CIT binding and recovery from depression

Abstract. Eighteen depressive outpatients were investigated using single-photon emission computerized tomography (SPECT) with a high-affinity dopamine (DA) and serotonin transporter (SERT) specific radioligand, ¹²³I-labeled -CIT (2-carbomethoxy-3-(4-iodophenyl)-tropane). The patients were tested at the beginning of the study and on follow-up after six months. The severity of depression was evaluated using the 17-item Hamilton Rating Scale of Depression (HRSD). Eight of the eighteen patients had an HRSD score below the median (12 points) on follow-up, and they had a significantly greater increase in ¹²³I--CIT binding in the midbrain region compared with those patients who did not recover (ANCOVA: F = 8.12; df = 1, 14; p = 0.013). These results indicate that recovery from depression is associated with an increase in ¹²³I--CIT binding in the midbrain.     

The murine <Emphasis Type="Italic">Bis1</Emphasis> seizure gene and the <Emphasis Type="Italic">Kcnab2</Emphasis> gene encoding the β2-subunit of the K<Superscript>+</Superscript> channel are different

Received: April 22, 1999 / Accepted: August 30, 1999 / Published online: January 10, 2000     

<Emphasis Type="Italic">N</Emphasis><Superscript>ε</Superscript>-Carboxymethyllysine in diabetic and non-diabetic polyneuropathies

Increased oxidative stress and advanced glycosylation are important factors in the development of diabetic neuropathy. In non-diabetic neuropathies their influence has not been investigated in detail so far. We studied the localisation of N(epsilon)-carboxymethyllysine (CML) - a biomarker for oxidative stress - by immunohistochemistry in sural nerve biopsies of 31 patients with different polyneuropathies [diabetic polyneuropathy (n=5), alcohol-associated polyneuropathy (n=4), vitamin B12-deficient polyneuropathy (n=6), chronic inflammatory demyelinating polyneuropathy (CIDP) (n=6), vasculitic neuropathy (n=6), Charcot-Marie-Tooth disease type I (CMT I) (n=4)] and 4 normal controls. CML was detected in the perineurium of patients with diabetic, alcohol-associated, vitamin B12-deficient and vasculitic polyneuropathies. Epineurial, perineurial and endoneurial vessels were CML positive in diabetic, vitamin B12-deficient and vasculitic polyneuropathies. CML was also found in mononuclear inflammatory cells in vasculitic neuropathy. In CIDP and normal controls there was only marginal perineurial CML deposition in 2/6 and 1/4 cases. In CMT I no CML was detected. Immunohistochemical results were confirmed by immunoblot. Our data suggest a role of oxidative stress in the pathogenesis not only of diabetic but also of alcohol-associated, vitamin B12-deficient and vasculitic polyneuropathies. It may be a minor pathogenetic factor in CIDP and may not be involved in CMT I. Underlying causes for increased oxidative stress may be an elevated production of reactive oxygen species and an impairment of antioxidative defences. Therefore, an antioxidative treatment should be considered in alcohol-associated, vitamin B12-deficient and vasculitic polyneuropathy.     

Amyloid-Positronenemissionstomographie mit [<Superscript>18</Superscript> F]-Florbetaben in der Demenzdiagnostik

Background

To this day the definite diagnosis of Alzheimer’s disease still relies on post-mortem histopathological detection of neurofibrillary tangles and beta-amyloid deposits. Amyloid positron emission tomography (PET) is a new diagnostic tool that enables the in vivo quantification of pathological beta-amyloid deposits. The aim of the current study was to evaluate to what extent ¹⁸F-florbetaben-PET (FBB-PET) influences the diagnosis of patients with dementia.

Material and methods

Imaging with FBB-PET was performed on 33 patients from our outpatient department for cognitive neurology. Beforehand all patients underwent a comprehensive clinical, neuropsychiatric and laboratory examination as well as imaging by means of magnetic resonance imaging (MRI) and fluorodeoxyglucose-PET. The working diagnoses before and after FBB-PET imaging were compared.

Results

17 out of 33 patients were scored as FBB-PET positive. In four cases the initial diagnosis had to be changed to Alzheimer’s disease (three cases) and cerebral amyloid angiopathy (one case) due to the positive FBB-PET scan. 16 patients showed a negative FBB-PET scan. In three patients the initial diagnosis of Alzheimer’s disease could be ruled out due to the negative FBB-PET scan. Overall, in 7 out of 33 examined patients the initial diagnosis had to be changed because of the findings of the FBB-PET scan. In 24 patients the initial diagnosis was confirmed by the results of the FBB-PET scan.

Conclusion

Amyloid-PET is currently no standard procedure in the diagnosis of dementia; however, it can be a helpful additional diagnostic tool when used according to the “Appropriate Use Criteria” and the S3 guidelines on dementia in cases of unclear clinical presentation, atypically early age of onset as well as in patients with persistent or progressive unexplained mild cognitive impairment. By facilitating early diagnosis amyloid-PET imaging allows patient selection for therapeutic drug trials.

     

New perspectives on neurochemical effects of amantadine in the brain of parkinsonian patients: a PET – [<Superscript>11</Superscript>C]raclopride study

Summary. Amantadine, is a non competitive NMDA receptors antagonist that has been proved beneficial in Parkinson's disease. However its mechanism of action at therapeutic doses is still under discussion. Aim of this study was to evaluate the effect of repeated administration of amantadine on striatal dopaminergic system by measuring [¹¹C]raclopride binding to striatal D₂ dopamine receptors, in patients with moderate idiopathic Parkinson's disease. Eight patients completed the study undergoing a PET scan, before and after 10–14 days treatment with Amantadine (200 mg/day). Patients were on treatment with L-DOPA, which was suspended 1 night before each PET scans, and free from dopaminergic agonists, anticholinergic and antidepressants. Amantadine treatment significantly increased [¹¹C-]Raclopride binding (caudate: 10% p = 0.04; putamen 11% p = 0.01). A slight reduction (−7.3%, p = 0.062) of UPDRS total scores was also observed. The increased availability of striatal D₂ receptors, is likely to be caused by drug induced modification of receptors expression. This hypothesis is consistent with previous experiments, indicating an increase in striatal D₂ receptors in rats treated with amantadine or other non competitive NMDA antagonists and suggests that the neo-synthesis of D₂ receptors may represent a reinforcing mechanism of drug efficacy. Received October 17, 2001; accepted January 3, 2002 Published online June 28, 2002     

CCL2 transgene expression in the central nervous system directs diffuse infiltration of CD45<Superscript>high</Superscript>CD11b<Superscript>+</Superscript> monocytes and enhanced Theiler’s murine encephalomyelitis virus-induced demyelinating disease

CCL2 is a member of the CC chemokine family that mediates the migration and recruitment of monocytes and T cells and has been identified in the central nervous system (CNS) during several neuroinflammatory diseases. In order to examine the biological effect of constitutive CCL2 expression in the CNS, the authors engineered a mouse that expressed CCL2 in the CNS under control of the human glial fibrillary acidic protein (hGFAP) promoter. The results demonstrated that transgenic expression of CCL2 in the CNS resulted in diffuse CNS monocyte infiltration and accumulation. Transgenic CCL2 expression did not alter normal development, differentiation, or function of T cells. There was no evidence of overt CNS disease or other pathologic phenotype when mice were left unchallenged with antigen or uninfected. However, when CCL2 transgenic mice were given a peripheral challenge of lipopolysaccharide (LPS), an inflammatory infiltrate with organized perivascular lesions developed. Infection of the transgenic mice with Theiler's murine encephalomyelitis virus (TMEV) resulted in accelerated onset and increased severity of clinical and histological disease. These results suggest that CCL2 expression in the CNS is a major pathogenic factor that drives macrophage accumulation in the development of CNS inflammatory disease.     

Predictors of adolescents’ mental health problems in Saudi Arabia: findings from the Jeeluna<Superscript>®</Superscript> national study

Background

Depression and anxiety among adolescents require further attention as they have profound harmful implications on several aspects of adolescents’ wellbeing and can be associated with life threatening risk behaviors such as suicide.

Objective

To examine the underlying risk factors for feeling so sad or hopeless and for feeling worried among adolescents in Saudi Arabia.

Methods

Data from Jeeluna^® national survey was used. A cross-sectional, multi-stage, stratified, cluster random sampling technique was applied among a sample of students aged 10–19 years attending intermediate and secondary schools in Saudi Arabia. A self-administered questionnaire assessing several domains, including feeling so sad or hopeless and worried, was used to collect data. Logistic regression models were fitted to determine the different factors associated with mental health.

Results

A sample of 12,121 students was included in this study. Feeling so sad or hopeless and feeling worried were significantly more prevalent among females and older adolescents (p < 0.0001). The results showed that poor relationship with parents, negative body image, and chronic illness to be significantly associated with feeling so sad or hopeless and worried.

Conclusions

Symptoms suggestive of mental health problems among adolescents in Saudi Arabia are prevalent and deserve special attention. Adopting effective strategies, including regular screening and intervention programs are highly needed to better address, detect, and control early signs of these problems.

     

Sapphire<Superscript>®</Superscript> platinum detachable coil experience in a tertiary-care facility

Background

The Guglielmi Detachable Coil introduced by the Boston Scientific Corporation has been widely used for endovascular coiling of aneurysm. Recently, Sapphire® platinum detachable coils (eV3, Irvine, CA) have been introduced for aneurysm coiling. Herein, we report our clinical experience with the Sapphire® coil to evaluate the incidence of coil related complications and the rate of aneurysm occlusion.

Methods

Consecutive patients who underwent embolization with Sapphire® detachable coils were prospectively enrolled from January 2004 to September 2004 and the data were retrospectively analyzed. Patient demographics, including age, gender, presenting symptoms, Hunt and Hess grade, Fisher grade and locations of the vascular anomalies were collected. Additionally, complications associated with the coils and rates of aneurysm occlusion were observed and the data compiled.

Results

29 patients underwent Sapphire® coil embolization for intracranial aneurysms. Mean age was 50 ± 18 (mean ± SD) years with 81% being females. Aneurysm neck reconstruction was required in 7 cases, 6 with Neuroform stent (5 unruptured aneurysms) and 1 with balloon assistance (ruptured aneurysm). In 7 cases, Sapphire® coils were used along with other coils. There were no events of thromboembolism or ruptures of aneurysms during coil embolization. However, multi-diameter coils demonstrated stretching in 4 stent-assisted cases without any adverse consequences. Complete occlusion of the aneurysm was achieved in 79.31% of the patients, neck remnant in 6.89, and partial coiling was achieved in 13.79%.

Conclusion

The Sapphire® coil could safely be used in the treatment of both ruptured and unruptured aneurysms. However, multi-diameter non-stretch resistant coils may be associated with coil stretching when used in conjunction with a stent. Further study is still required for definitive results.

     

Identification of N<Superscript>ɛ</Superscript>-(carboxymethyl)lysine-positive cells in astroglia-rich primary cultures

Summary. Astroglia-rich primary cultures from rat brain were used to investigate the presence in glial cells of N-(carboxymethyl)lysine (CML), an advanced glycation endproduct. Westernblot analysis of homogenates of rat brain as well as of astroglia-rich cultures demonstrated the presence of CML-modified proteins in these samples. Immunocytochemical staining of astroglia-rich cultures revealed that only a minority of the cells in these cultures were intensively stained for CML. The staining intensity of CML-positive cells was strongly reduced, if the cells were not permeabilized, indicating that intracellular proteins were CML-modified. The CML-positive cells were identified as astrocytes and oligodendrocytes by double-labelling immunocytochemical staining for CML and the cellular markers galactocerobroside, myelin basic protein and glial fibrillary acidic protein. In contrast to other glial cells, microglial cells in astroglia-rich cultures were CML-negative. The finding that only a minority of cells in astroglia-rich cultures contains high amounts of intracellular CML-modified proteins indicates that specific properties of these CML-positive cells are responsible for the CML-formation in these cells.Received January 28, 2003; accepted April 22, 2003 Published online June 30, 2003     

Delta-9-Tetrahydrocannabinol (∆<Superscript>9</Superscript>-THC) Induce Neurogenesis and Improve Cognitive Performances of Male Sprague Dawley Rats

Neurogenesis is influenced by various external factors such as enriched environments. Some researchers had postulated that neurogenesis has contributed to the hippocampal learning and memory. This project was designed to observe the effect of Delta-9-tetrahydrocannabinol (?⁹-THC) in cognitive performance that influenced by the neurogenesis. Different doses of ?⁹-THC were used for observing the neurogenesis mechanism occurs in the hippocampus of rats. The brains were stained with antibodies, namely BrdU, glial fibrillary acidic protein (GFAP), nestin, doublecortin (DCX) and class III β-tubulin (TuJ-1). The cognitive test was used novel-object discrimination test (NOD) while the proteins involved, DCX and brain-derived neurotrophic factor (BDNF), were measured. Throughout this study, ?⁹-THC enhanced the markers involved in all stages of neurogenesis mechanism. Simultaneously, the cognitive behaviour of rat also showed improvement in learning and memory functions observed in behavioural test and molecular perspective. Administration of ?⁹-THC was observed to enhance the neurogenesis in the brain, especially in hippocampus thus improved the cognitive function of rats.     

LEGO<Superscript><Emphasis Type="Bold">®</Emphasis></Superscript> Therapy and the Social Use of Language Programme: An Evaluation of Two Social Skills Interventions for Children with High Functioning Autism and Asperger Syndrome

LEGO therapy and the Social Use of Language Programme (SULP) were evaluated as social skills interventions for 6-11 year olds with high functioning autism and Asperger Syndrome. Children were matched on CA, IQ, and autistic symptoms before being randomly assigned to LEGO or SULP. Therapy occurred for 1 h/week over 18 weeks. A no-intervention control group was also assessed. Results showed that the LEGO therapy group improved more than the other groups on autism-specific social interaction scores (Gilliam Autism Rating Scale). Maladaptive behaviour decreased significantly more in the LEGO and SULP groups compared to the control group. There was a non-significant trend for SULP and LEGO groups to improve more than the no-intervention group in communication and socialisation skills.     

Down-regulation of the AMPA glutamate receptor subunits GluR1 and GluR2/3 in the rat cerebellum following pre- and perinatal Δ<Superscript>9</Superscript>-tetrahydrocannabinol exposure

This paper reports the effects of pre- and perinatal exposure to delta9-tetrahydrocannabinol (THC) on expression levels of specific AMPA glutamate receptor subunits (GluR1 and GluR2/3) in the cerebellum of male and female rats. Pregnant rats were administered saline or THC from gestational day 5 (ED5) to postnatal day 20 (PD20). Expression of the GluR1 and GluR2/3 subunits of AMPA glutamate receptors was analyzed by immunohistochemistry in THC-exposed rats at three postnatal ages: PD20 (still exposed to THC) to study the direct effect of drug exposure, and PD30 and PD70 (10 and 50 days following THC withdrawal) to analyze the long-term effects of prenatal exposure. Compared to controls, pre- and perinatal THC exposure decreased the immunoreactivity levels of the GluR1 subunit in Bergmann glial cells, as well as levels of the GluR2/3 subunit in Purkinje neurons at PD20. These changes in AMPA receptor subunit levels may correlate with the decreased excitatory neurotransmission described in the cerebellum after cannabinoid treatment, which could play a significant role in the biochemical effects of THC. In addition, the reduced glutamate receptor expression observed at PD20 did not return to normal even after THC withdrawal (PD30 and PD70). The results support the idea that THC exposure during critical stages of cerebellar development may alter the glutamatergic system, not only during the drug exposure period itself but also in adults following THC withdrawal. The decreased expressions of glutamate receptors induced by developmental THC exposure could lead to functional alterations through the inhibition of glutamatergic neurotransmission, and clearly demonstrate an interaction between cannabinoids and the glutamatergic system.     

Discrimination of white matter lesions and multiple sclerosis plaques by short echo quantitative <Superscript>1</Superscript>H—magnetic resonance spectroscopy

Multiple sclerosis (MS) plaques and age related white matter lesions (WML) are of similar morphological appearance on T2 weighted MRI. Therefore their differentiation is sometimes crucial. Proton magnetic resonance spectroscopy (¹H–MRS) adds metabolic information to conventional imaging and may help to distinguish inflammatory MS plaques from vascular related WML. This study was performed to evaluate the metabolite pattern in MS plaques and WML. 15 MS patients, 14 elderly individuals with WML and 16 controls were investigated by conventional MRI and short echo quantitative ¹H–MRS (TE: 30ms, TR: 3000ms). The mean metabolite concentrations in normal control white matter (NCWM), MS plaques and WML were: t–NAA: 8.96 mmol/l (SD:0.93) vs 6.79 mmol/l (SD: 1.99) vs 7.18 mmol/l (SD: 1.41); Cho: 1.66 mmol/l (SD: 0.4) vs 1.49 mmol/l (SD: 0.45) vs 1.46 mmol/l (SD: 0.34); PCr: 5.64 mmol/l (SD: 0.83) vs 4.9mmol/l (SD: 1.3) vs 4.95 mmol/l (SD: 0.86); myo–Ins: 4.57 mmol/l (SD:1.05) vs 6.34 mmol/l (SD: 2.03) vs 4.5 mmol/l (SD: 0.96). t–NAA reduction in MS plaques and WML was significant compared with controls (p ≤ 0.001). MS plaques showed significantly elevated myo– Ins concentrations compared with controls (p = 0.002) and to WML (p = 0.003). In summary MS plaques and WML show a decrease in their t–NAA concentrations compared with controls. Elevated concentrations of myo–Ins in MS plaques but not in WML makes this metabolite of special interest for their differentiation.     

Pharmacological Effects on Ceroid Lipofuscin and Neuronal Structure in <Emphasis Type="Italic">Cln3</Emphasis><Superscript><Emphasis Type="Italic">∆ex7/8</Emphasis></Superscript> Mouse Brain Cultures

Juvenile Batten disease (JBD) is an inherited disorder that is characterized by the development of blindness, seizures, and progressive motor, psychiatric, and cognitive impairment. A model of JBD expressing the predominant human mutation (Cln3 ^?ex7/8 ) has been explored. Dissociated brain cultures from Cln3 ^?ex7/8 knock-in mice were compared to wild type (WT) for effects on granules of ceroid lipofuscin (CL) and neuronal structure. Utilizing high content image analysis of CL granules identified with antibodies to mitochondrial ATP synthase subunit c or tripeptidyl peptidase-1, significant increases in the areas for both immunoreactive granules were observed in Cln3 ^?ex7/8 cultures in comparison to WT. CL granules also exhibit autofluorescence at 488 and 560 nm, and the areas of these autofluorescent spots were found to be significantly increased in Cln3 ^?ex7/8 cultures in comparison to WT. Progressive increases in CL granule area in Cln3 ^?ex7/8 cultures were observed during culture development. Because current therapies for JBD provide only symptomatic support, a therapeutic strategy has been explored based on the observations that JBD-related tissues are deficient in β-galactosyl ceramide. Treatment of cultures for 40 h with a potent analog of β-galactosyl ceramide (SNB-4050) produced significant decreases in CL granule area in the Cln3 ^?ex7/8 cultures; whereas identical studies on WT cultures produced no detectible changes. Significant decreases in average neurite length and neurite branch point number were also observed in the Cln3 ^?ex7/8 cultures that were attenuated by treatment with 1 nM SNB-4050. These studies indicate Cln3 ^?ex7/8 brain cultures may be useful to screen therapeutic agents for treatment of JBD.     

<Emphasis Type="Italic">Euphorbia hirta</Emphasis> reverses chronic stress-induced anxiety and mediates its action through the GABA<Subscript>A</Subscript> receptor benzodiazepine receptor-Cl<Superscript>−</Superscript> channel complex

Summary. Chronic stress is known to result in impairment of learning and memory and precipitate several affective disorders including depression and anxiety. Drugs of natural origin are known to possess several effects on the central nervous system and are emerging as promising alternative therapies. In this context, the hydroalcoholic extract of Euphorbia hirta (Eh) was evaluated for anxiolytic property in chronically stressed rats subjected to elevated plus maze (EPM) and open field test (OFT). Eh treatment (200 mg/kg, p.o.; seven days) showed marked anti-anxiety activity in chronic immobilization stress. In contrast, the forced swim stress-induced anxiety was only partially decreased by Eh. Co-treatment of rats with flumazenil (0.5 mg/kg, i.p.), bicuculline (1 mg/kg, i.p.) or picrotoxin (1 mg/kg, i.p.) resulted in a significant reduction of anxiolytic effect of Eh indicating that its actions are mediated through GABA_A receptor-benzodiazepine receptor-Cl⁻ channel complex. Thus, our studies indicate that Eh is a potential anxiolytic drug, which might be beneficial in the treatment of stress-induced anxiety disorders. Correspondence: B. S. Shankaranarayana Rao, Department of Neurophysiology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, PB 2900, Bangalore 560 029, India     

Efficacy of St. John’s wort extract WS<Superscript>®</Superscript> 5570 in acute treatment of mild depression

Based on the original data from two double-blind, randomized, placebo-controlled clinical trials and the acute phase of a long-term study that investigated the antidepressant efficacy of St. John’s wort extract WS^® 5570, we present a re-analysis of a subset of patients suffering from an acute episode of mild depression according to DSM criteria. Out of a total of more than 1,200 patients included into these trials 217 had a pre-treatment total score ≤20 points on the 17-item Hamilton Rating Scale for Depression (HAMD) and were eligible for our re-analysis. They received 600, 900, or 1,200 mg/day WS^® 5570 or placebo for 6 weeks. In patients treated with WS^® 5570 the HAMD total score decreased by averages of 10.8 (600 mg/day), 9.6 (900 mg/day), and 10.7 (1,200 mg/day) points between the pre-treatment baseline value and the end of acute treatment, compared to 6.8 points in the placebo group (p < 0.01 for all pairwise comparisons of WS^® 5570 against placebo). This corresponded to average relative decreases by 49–57% for WS^® 5570 and by 36% for placebo. The rates of responders (i.e., patients with a HAMD total score decrease ≥50%) were 73%, 64%, 71%, and 37% for WS^® 5570 600 mg/day, 900 mg/day and 1,200 mg/day, and placebo, respectively. At the end of acute treatment 57% of the patients treated with WS^® 5570 600 mg/day, 33% in the 900 mg/day group and 62% in the 1,200 mg/day group, as well as 25% in the placebo group were in remission (HAMD total score ≤7 points). The analysis shows that St. John’s wort extract WS^® 5570 has a meaningful beneficial effect during acute treatment of patients suffering from mild depression and leads to a substantial increase in the probability of remission.