Nitric oxide and peroxynitrite have different antiviral effects against hantavirus replication and free mature virions

Reactive nitrogen intermediates (RNI), like nitric oxide (NO) and peroxynitrite, have antiviral effects against certain viruses. Hantaviruses, like other members of the Bunyaviridae family, have previously not been shown to be sensitive to RNI. In this study, we compared the effects of NO and peroxynitrite on hantavirus replication and free mature virions in vitro, and of inducible nitric oxide synthase (iNOS) in hantavirus-infected suckling mice. The NO-generating compound S-nitroso-N-acetylpenicillamine (SNAP), as well as cytokine-induced NO, strongly inhibited hantavirus replication in Vero E6 cells, while pretreatment of free virions with SNAP only had a limited effect on their viability. In contrast, 3-morpholinosydnonimine hydrochloride (SIN-1), a peroxynitrite donor, inhibited virus replication only to a very low extent in vitro, but pretreatment of virus with SIN-1 led to a considerably lowered viability of the virions. Infections of various human cell types per se did not induce NO production. The viral titers in iNOS(-/-) mice were higher compared to the controls, suggesting that NO inhibits hantavirus replication in vivo. In conclusion, we show that NO has strong antiviral effects on hantavirus replication, and peryoxynitrite on mature free virions, suggesting that different RNI can have different effects on various parts of the replication cycle for the same virus.     

How painful is multichannel urodynamic testing?

Introduction and hypothesis  Multichannel urodynamic testing is considered to be the gold standard for evaluation of lower urinary tracts symptoms in women. The objective of this study was to assess the level of pain associated with this test. Methods  We reviewed charts of women who underwent multichannel urodynamic testing for lower urinary tract symptoms and recorded pain levels using a validated visual analog pain scale of 0–10 before, during, and 1.5 h after the test. Results  We identified 50 patients who underwent the test. Pain level increased mildly but significantly during the urodynamic test (1.24 ± 0.9 vs 0.02 ± 0.14 p < 0.001) and decreased thereafter (0.1 ± 0.35, p < 0.001). Conclusions  Multichannel urodynamic testing is associated with a low but significant level of pain, which generally abates shortly after the procedure. No correlation seems to exist between the degree of pain and various clinical and pelvic floor parameters.     

D-serine adjuvant treatment alleviates behavioural and motor symptoms in Parkinson's disease

Parkinson's disease (PD) manifestations include motor symptoms and behavioural deficits that resemble schizophrenia negative symptoms. The N-methyl-D-aspartate subtype of glutamate receptor (NMDAR) represents a novel pharmacological target in PD. D-serine (DSR) allosterically modulates in-vivo NMDAR-mediated neurotransmission and has been shown to improve negative and antipsychotic drug-induced parkinsonian symptoms in schizophrenia patients. This pilot study assessed DSR effects in ten PD patients who completed a 6-wk double-blind, placebo-controlled, crossover adjuvant treatment trial with 30 mg/kg.d DSR. Primary outcome analyses consisted of separate repeated-measures multivariate analyses of variance for Unified Parkinson's Disease Rating Scale (UPDRS), Simpson-Angus Scale for Extrapyramidal Symptoms (SAS), Abnormal Involuntary Movement Scale (AIMS), and Positive and Negative Syndrome Scale (PANSS) scores. DSR treatment was well tolerated and resulted in increased DSR serum levels (p=0.001) and significantly reduced UPDRS (p=0.02), SAS (p=0.009) and PANSS (0.05) total scores. These preliminary findings suggest that DSR treatment may be beneficial in PD. Larger-sized studies with optimized DSR dosages are warranted.     

Do mood disorders alter crying? a pilot investigation

Clinical commentators widely interpret crying as a sign of depressed mood. However, there is virtually no empirical data on this topic, and the evidence that mood disorders alter crying is surprisingly weak. This study compared mood disordered patients to a nonpsychiatric reference group on the frequency, antecedents, and consequences of crying behavior using a well-validated questionnaire measure of crying. Forty-four outpatients diagnosed with three forms of mood pathology were age and gender matched to a reference group of 132 participants sampled to be representative of the Dutch population. Both groups completed the Adult Crying Inventory, which provides estimates of the self-reported frequency, antecedents, and consequences of crying behavior. Depression severity and psychiatric symptom severity data were also collected from patients. Compared with the reference group, patients with mood pathology reported increased cry proneness to negative antecedents. By contrast, patients and controls did not differ in reported cry proneness to positive antecedents. Patients reported less mood improvement after crying than did controls. Among male patients, but not female patients, depression severity was associated with increased crying proneness and increased crying frequency. This pilot investigation suggests that mood disorders increase the frequency of negative emotional crying, and may also alter the functions of this behavior. Mood disorders may influence male crying to a greater extent than female crying. Future directions designed to clarify the causal pathways between mood disorders and alterations in crying behavior are discussed.     

Adjusting a light dispersion model to fit measurements from vertebrate ocular media as well as ray-tracing in fish lenses

Color dispersion, i.e., the dependency of refractive index of any transparent material on the wavelength of light, has important consequences for the function of optical instruments and animal eyes. Using a multi-objective goal attainment optimization algorithm, a dispersion model was successfully fitted to measured refractive indices of various ocular media and the longitudinal chromatic aberration determined by laser-scanning in the crystalline lens of the African cichlid fish, Astatotilapia burtoni. The model describes the effects of color dispersion in fish lenses and may be applicable to the eyes of other vertebrates as well.