Glutamine restores testicular glutathione-dependent antioxidant defense and upregulates NO/cGMP signaling in sleep deprivation-induced reproductive dysfunction in rats.

Oxidative stress has been linked with sleep deprivation (SD)-induced pathological conditions and reproductive dysfunction. On the other hand, glutamine has been established to have antioxidant property. However, the impact of SD, with or without glutamine, on male reproductive function is yet to be elucidated. Thus, this study was designed to investigate the role of SD, with or without glutamine, on male reproductive function and possible associated mechanisms. Ten-week old male Wistar rats weighing 175.6 g± 0.42 were randomly assigned into vehicle that received per os (p.o.) distilled water, glutamine (1 g/kg; po), SD, and SD + glutamine that received treatments as glutamine and SD. Treatment/exposure lasted for 72 h. The results showed that SD led to reduced body weight, seminiferous luminal and epididymal sperm density, low sperm quality, increased testicular and epididymal malondialdehyde, uric acid, DNA fragmentation, and testicular injury markers. In addition, SD caused a reduction in reduced glutathione level and activities of superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, glutathione peroxidase, and glutathione-S-transferase. Also, SD increased tumor necrotic factor-α, interleukin-1ß, and nuclear factor-kappa B levels. Furthermore SD led to impaired libido and erectile dysfunction, and suppression of circulatory nitric oxide, gonadotropins and testosterone, and penile cGMP. However, glutamine attenuated the effects induced by SD. Taken together, the findings of this study demonstrate that SD induces reproductive dysfunction via glutathione-dependent defense depletion and down-regulation of NO/cGMP signaling, which was abolished by glutamine supplementation.

Improved detection of bacterial central nervous system infections by use of a broad-range PCR assay.

A universal PCR assay for bacteria and fungi detected meningitis pathogens in 65% of 20 cerebrospinal fluid (CSF) samples from patients with suspected central nervous system (CNS) infections compared to a 35% detection rate by culture and/or microscopy methods. Thus, the PCR assay can improve the diagnosis rate of infective meningitis when standard methods provide a negative result.

Treatment of steroid-unresponsive optic neuritis with plasma exchange.

OBJECTIVES: Until now, the significance of plasma exchange (PE) as a treatment for steroid-unresponsive optic neuritis (ON) is still unclear because placebo-controlled and larger studies are missing. We report our experience with 23 patients treated by PE due to steroid-unresponsive ON. MATERIALS AND METHODS: Patients were admitted to the University Medical Center Hamburg-Eppendorf between 2006 and 2010 with a visual acuity of <50% on the affected eye following steroid treatment. Ten patients suffered from RR-MS, one from neuromyelitis optica, and 12 patients developed ON as a clinically isolated syndrome. Routinely, they were treated with five cycles of PE. Visual acuity was measured before and directly after PE and during follow-up (first follow-up after 50 days, second follow-up after 174 days). RESULTS: Altogether, 70% of our patients improved after PE, 69% of them showed a good or very good response to therapy. Patients who improved well after PE (n = 11) showed a mean visual acuity of 16% before PE compared to 45% immediately after PE and 60% at the first follow-up. No serious adverse events occurred. CONCLUSIONS: To our knowledge, our study is the largest case series of patients with steroid-unresponsive ON treated with PE. Based on our experience, we conclude that PE is an important treatment option for patients with steroid-unresponsive ON although placebo-controlled studies are missing until now.

Long-term outcome after angioplasty of symptomatic internal carotid artery stenosis with and without stent.

INTRODUCTION: Carotid angioplasty and stenting (CAS) has widely replaced balloon angioplasty (percutaneous transluminal angioplasty, PTA) in the treatment of internal carotid artery stenosis (ICAS). Here we assess whether the use of stents increases the safety and long-term efficacy of angioplasty in patients with ICAS. Our aim was to test the hypothesis that the long-term efficacy of CAS is superior to that of PTA. METHODS: At the University Medical Center Hamburg-Eppendorf, PTA was performed from 1990 to 1997 and CAS was performed from 1998 to 2006. All patients undergoing these procedures were symptomatic. Selection and follow-up examinations were performed by independent vascular neurologists. Follow-up terms were 1, 3, 6 and 12 months, then annually. RESULTS: In the PTA group (n=71), 2.8% of the patients showed severe periinterventional complications (i.e. lasting neurological deficits). Of these 71 patients, 57.7% were followed up for an average period of 51 months. Stenosis >70% was observed in 9.8% of the PTA patients, while 4.9% of the patients had ipsilateral occlusions. In the CAS group (n=354), 4.2% of the patients showed severe periinterventional complications. In total, 61% of the CAS patients were followed up for an average period of 25 months, of whom 4.6% showed stenosis of >70% and 1.9% had ipsilateral occlusions. Periprocedural complications and new symptoms that appeared during follow-up occurred at a rate of 5.6% (PTA) and 5.9% (CAS). There was no difference in the rate of annual ipsilateral events (1.1% in PTA vs. 1.3% in CAS, p=1.000) CONCLUSION: Overall, the use of stents, rather than PTA only, shows no beneficial clinical effect in the treatment of ICA stenosis. While the rate of restenosis may be significantly reduced, this merely suggests that the impact of restenosis is less apparent than expected.

PEGylation of microspheres generates a heterogeneous population of particles with differential surface characteristics and biological performance.

Surface PEGylation of polystyrene microspheres with methoxy-poly(ethylene glycol)-5000 (mPEG-5000) generated a heterogeneous population of entities that differed in surface characteristics and in vitro biological performance (phagocytosis and complement activation). Surface heterogeneity was determined by hydrophobic interaction chromatography, measurements of particle electrophoretic mobility in a defined field and adlayer thickness of the projected mPEG chains. The particle population separation by hydrophobic interaction chromatography demonstrated a remarkable linear relationship between the particle zeta potential and phagocytosis by J774 A1 macrophage-like cells. Microsphere populations bearing a predominant surface of mPEG molecules as high-density mushroom-brush intermediate and/or brush configuration were most resistant to phagocytosis and activated the human complement system poorly. Conversely, those populations with predominant surface mPEGs in a mushroom regime were potent activators of the complement system and were prone to phagocytosis. Therefore, surface heterogeneity explains why a fraction of intravenously injected 'long-circulating' nanoparticles is cleared rapidly by macrophages of the reticuloendothelial system. Hydrophobic interaction chromatography can readily assess the extent of surface heterogeneity of PEGylated particulate drug delivery systems and pre-select particles with optimal retention times in the blood. These observations may also be relevant with respect to successful surface camouflaging of cells, drug depots and implantable devices.

Visual recovery in a man with the rare combination of mtDNA 11778 LHON mutation and a MS-like disease after mitoxantrone therapy.

We describe a young man with prognostic unfavourable homoplasmatic mitochondrial DNA(mt DNA) 11778 Leber's hereditary optic neuropathy (LHON) point mutation and confirmed multiple sclerosis (MS). This combination of LHON and MS-like disease is rare in both sexes, and in men has been described in only a few case reports. In a 4-year follow-up during immunosuppressive therapy with mitoxantrone, we found a remarkable time delayed visual recovery 12 months after acute onset of rapid sequential bilateral subtotal visual loss followed by episodes of isolated acute demyelinative optic neuropathy. Visual recovery to such extent after this latency is uncommon in both mtDNA 11778 LHON mutation and optic neuritis (ON) in MS. Relapses in visual deterioration must be considered as extremely rare in LHON. This case might support the hypothesis of an immunological pathogenetic factor in combined LHON and MS, and possibly in LHON alone. We suggest a search for the LHON mutation in MS patients with predominant visual impairment, independent of patients' gender.

Failure of ondansetron in treating cerebellar tremor in MS patients--an open-label pilot study.

Cerebellar tremor is a frequent and disabling symptom in multiple sclerosis (MS) patients. Supportive pharmacological treatment with different drugs showed only minor effects in a few studies and in clinical practice. Encouraged by previous studies with ondansetron, a 5HT3-antagonist, we conducted a small open-label, prospective and controlled study with 14 MS patients suffering predominantly from cerebellar tremor of the upper extremities. Principal outcome measure to evaluate a functional improvement of the single intravenous administered ondansetron injection was the subject performance in the 9-hole-peg-test (9HPT) and 3 blind assessed upper extremity writing and copying tasks. We neither found significant improvement in the upper extremity tests nor in the subjective response of the patients. In conclusion we could not confirm a beneficial effect of ondansetron on cerebellar tremor of MS patients.

Visual imagery in hemianopic patients.

In this article we report some findings about visual imagery in patients with stable homonymous hemianopia compared to healthy control subjects. These findings were obtained by analyzing the gaze control through recording of eye movements in different phases of viewing and imagery. We used six different visual stimuli for the consecutive viewing and imagery phases. With infrared oculography, we recorded eye movements during this presentation phase and in three subsequent imagery phases in absence of the stimulus. Analyzing the basic parameters of the gaze sequences (known as "scanpaths"), we discovered distinct characteristics of the "viewing scanpaths" and the "imagery scanpaths" in both groups, which suggests a reduced extent of the image within the cognitive representation. We applied different similarity measures (string/vector string editing, Markov analysis). We found a "progressive consistency of imagery," shown through raising similarity values for the comparison of the late imagery scanpaths. This result suggests a strong top-down component in picture exploration: In both groups, healthy subjects and hemianopic patients, a mental model of the viewed picture must evolve very soon and substantially determine the eye movements. As our hemianopic patients showed analogous results to the normal subjects, we conclude that these patients are well adjusted to their deficit and, despite their perceptual defect, have a preserved cognitive representation, which follows the same top-down vision strategies in the process of visual imagery.

Disease specific quality of life instruments in multiple sclerosis: validation of the Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS).

Quality of life (QoL) is discussed as an additional outcome measure in multiple sclerosis (MS). However, few questionnaires assessing disease specific QoL in MS have been published. On the basis of the literature and interviews with clinicians and MS patients, we have developed a disease specific QoL instrument and validated it in a broad range of patients with MS. In this study, a heterogeneous sample of n = 237 MS patients completed the newly developed Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS, in German language) and a battery of already validated questionnaires. They further underwent neurological scoring and objective tests. By these means, we investigated its validity, appropriateness, internal consistency, and retest reliability. Internal consistency and retest coefficients were high and satisfied psychometric standards. Convergent and discriminant validity was supported by direction, magnitude and pattern of correlations with other health measures. HAQUAMS subscales and its total score distinguished between patient groups of varied disease severity, cognitive impairment, and affective symptomatology. No floor or ceiling effects were found in either of the HAQUAMS subscales. The HAQUAMS is a reliable, valid and appropriate instrument for QoL assessment in multiple sclerosis. Data of responsiveness are currently being obtained.

CD95-mediated apoptosis and DNA fragmentation in MS.

OBJECTIVE: To investigate possible associations of soluble CD95 (sCD95) serum levels and DNA defragmentation with different MS disease stages and activities. METHODS: Sera of 114 patients were analysed by an ELISA technique for sCD95. In a subgroup of 18 relapsing-remitting MS patients and controls we studied DNA fragmentation by the TUNEL-method in CSF cytospins. RESULTS: sCD95 was detectable in sera of MS patients, healthy controls and meningitis patients without significant differences. CSF specimens showed modest amounts of apoptotic cells in MS and controls. CONCLUSION: We could not demonstrate an association of MS disease course or activity with the expression of sCD95 in sera. DNA fragmentation in the CSF was not significantly enhanced compared to controls. Thus the analysed markers of programmed cell death appear not suitable to monitor MS disease courses.

IL-1ra serum levels in disease stages of MS--a marker for progression?

Interleukin-1 (IL-1) is one of the major proinflammatory cytokines expressed consistently in multiple sclerosis (MS) lesions. Interleukin-1 receptor antagonist (IL-1ra) is the only known naturally occurring specific antagonistic cytokine counteracting IL-1. Thus IL-1ra may have a downregulating potential in the disease course of MS. We analysed if circulating IL-1ra could be associated with different disease stages of MS in sera of 84 MS patients and 18 controls. IL-1ra showed considerable variations in MS patients and controls. Nevertheless we found significantly elevated serum levels in active as well as in stable disease stages compared to controls. IL-1ra levels were higher in progressive disease courses compared to relapsing-remitting MS, but not statistically significant (median: 516 versus 434 pg/ml). Further analysis with larger groups of patients and longitudinal studies will clarify if IL-1ra is useful as a prognostic serum marker in MS.