Management of peripheral facial nerve palsy

Peripheral facial nerve palsy (FNP) may (secondary FNP) or may not have a detectable cause (Bell’s palsy). Three quarters of peripheral FNP are primary and one quarter secondary. The most prevalent causes of secondary FNP are systemic viral infections, trauma, surgery, diabetes, local infections, tumor, immunological disorders, or drugs. The diagnosis of FNP relies upon the presence of typical symptoms and signs, blood chemical investigations, cerebro-spinal-fluid-investigations, X-ray of the scull and mastoid, cerebral MRI, or nerve conduction studies. Bell’s palsy may be diagnosed after exclusion of all secondary causes, but causes of secondary FNP and Bell’s palsy may coexist. Treatment of secondary FNP is based on the therapy of the underlying disorder. Treatment of Bell’s palsy is controversial due to the lack of large, randomized, controlled, prospective studies. There are indications that steroids or antiviral agents are beneficial but also studies, which show no beneficial effect. Additional measures include eye protection, physiotherapy, acupuncture, botulinum toxin, or possibly surgery. Prognosis of Bell’s palsy is fair with complete recovery in about 80% of the cases, 15% experience some kind of permanent nerve damage and 5% remain with severe sequelae

Structural and mechanistic insights into 5-lipoxygenase inhibition by natural products

© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. Leukotrienes (LT) are lipid mediators of the inflammatory response that are linked to asthma and atherosclerosis. LT biosynthesis is initiated by 5-lipoxygenase (5-LOX) with the assistance of the substrate-binding 5-LOX-activating protein at the nuclear membrane. Here, we contrast the structural and functional consequences of the binding of two natural product inhibitors of 5-LOX. The redox-type inhibitor nordihydroguaiaretic acid (NDGA) is lodged in the 5-LOX active site, now fully exposed by disordering of the helix that caps it in the apo-enzyme. In contrast, the allosteric inhibitor 3-acetyl-11-keto-beta-boswellic acid (AKBA) from frankincense wedges between the membrane-binding and catalytic domains of 5-LOX, some 30 Å from the catalytic iron. While enzyme inhibition by NDGA is robust, AKBA promotes a shift in the regiospecificity, evident in human embryonic kidney 293 cells and in primary immune cells expressing 5-LOX. Our results suggest a new approach to isoform-specific 5-LOX inhibitor development through exploitation of an allosteric site in 5-LOX. [Figure not available: see fulltext.]

Co-infecção HIV/HCV em pacientes de Botucatu e região HIV/HCV co-infection in patients from Botucatu and region (Brazilian cities)

Devido à similaridade nas rotas de transmissão, a co-infecção HIV/HCV é freqüente, afetando em média 30 a 50% dos portadores de HIV. O presente estudo visou avaliar uma possível associação entre os subtipos do HIV e genótipos do HCV em pacientes co-infectados, com base na análise das freqüências em pacientes mono e co-infectados. Para determinação da freqüência dos subtipos HIV e genótipos HCV, foram analisados respectivamente 124 e 496 pacientes mono-infectados. O estudo da co-infecção foi realizado num grupo de 150 pacientes HIV positivos e esteve presente em 22 (14,7%) dos pacientes. A freqüência dos subtipos do HIV-1 em mono-infectados foi: subtipo B (85,5%), subtipo F (12,9%) e recombinante B/F (1,6%), enquanto nos genótipos HCV foi: 1a (25%), 1b (29,4%), 1a/1b (3,6%), 3a (35%), 2 (1,8%) e 5 (0,4%). Nos co-infectados o padrão de distribuição dos subtipos HIV-1 é semelhante aos mono-infectados, ou seja, subtipo B (85,0%), seguido do subtipo F (15,0%). A distribuição de freqüência de genótipos HCV nos co-infectados foi: 1a (36,3%), 1b (27,3%), 1a/1b (9,1%) e 3a (27,3%) mostrando um aumento de 10% na freqüência do genótipo 1, queda de 7,7% no genótipo 3 e ausência de outros genótipos. A análise estatística de associação entre os subtipos HIV e genótipos HCV (Goodman) mostrou que no genótipo 1 (HCV) ocorreu predominância do subtipo B, enquanto no genótipo 3 (HCV) a distribuição dos subtipos B e F (HIV-1) foi casual. Isto aponta para a necessidade de mais estudos desse grupo e um maior valor amostral.<br>HIV/HCV co-infection is a frequent event due to the similarity of the means of transmission of both viruses; 30-50% of HIV infected individuals are co-infected¹. This paper assesses the possible association among HCV and HIV genotypes in co-infected patients based on frequency distribution in mono and co-infected patients. To determine HIV and HCV genotype frequency 124 and 496 respectively, mono infected patients were analyzed. The study of co-infection was performed in 150 HIV positive patients and 22 (14.7%) patients were found. The frequency of HIV-1 subtypes was 106 B subtype (85.5%), 16 F (12.9%), and 2 B/F recombinant (1.6%); HCV genotypes were 1a (25%), 1b (29.4%), 1a/1b (3.6%), 3a (35%), 2 (1.8%) and 5 (0.4%). The HCV genotype could not be determined in 6.3% of samples using the technique. The HIV-1 subtype distribution standard was B subtype (85.0%) and F subtype (15.0%) in mono-infected as in co-infected. The frequency distribution of HCV genotypes in co-infected was 1a (36.4%), 1b (27.3%), 1a/1b (9.1%) and 3a (27.3%). These results showed a 10% increase in frequency of 1a genotype, 7.7% decrease in 3 genotype and lack of other genotypes. The statistical analysis of association of HCV genotypes and HIV-1 subtypes (Goodman Test) showed a predominance of the B HIV subtype among HCV genotype 1, and among HCV genotype 3 the distribution of B and F HIV subtypes was casual. These results suggest the need for further studies in this group and larger samples

Time to face the fats: What can mass spectrometry reveal about the structure of lipids and their interactions with proteins?

Free to read at publisher Since the 1950s, X-ray crystallography has been the mainstay of structural biology, providing detailed atomic-level structures that continue to revolutionize our understanding of protein function. From recent advances in this discipline, a picture has emerged of intimate and specific interactions between lipids and proteins that has driven renewed interest in the structure of lipids themselves and raised intriguing questions as to the specificity and stoichiometry in lipid-protein complexes. Herein we demonstrate some of the limitations of crystallography in resolving critical structural features of ligated lipids and thus determining how these motifs impact protein binding. As a consequence, mass spectrometry must play an important and complementary role in unraveling the complexities of lipid-protein interactions. We evaluate recent advances and highlight ongoing challenges towards the twin goals of (1) complete structure elucidation of low, abundant, and structurally diverse lipids by mass spectrometry alone, and (2) assignment of stoichiometry and specificity of lipid interactions within protein complexes

Assessment of sleep-related disorders in children with sickle cell disease

Sleep-related disorders (SRDs) are common in sickle cell disease, however, identification may be time-consuming. Simultaneous survey of multiple SRDs utilizing a simplified instrument would facilitate screening. A simplified questionnaire investigating SRDs [sleep-disordered breathing (SDB), restless legs syndrome (RLS), insomnia, parasomnias, and daytime effects of disrupted sleep] was administered to 2-18-year-old children with sickle cell disease. One hundred participants completed this 5-7 minute survey without difficulties: 54 awoke unrefreshed, 41 had short-term insomnia, 30 had sleep-maintenance insomnia, 21 had chronic sleep-onset insomnia, 54 had chronic habitual snoring and 11 met the criteria for RLS. Sleep-maintenance insomnia was associated with increased body mass index (BMI) (p = 0.001), and chronic sleep-onset insomnia was associated with higher hemoglobin (Hb) levels (p = 0.04). Survey-reported symptoms of SRDs were significantly higher than that reported in the general pediatric population. A fast and simplified SRD survey is feasible and suggests a high prevalence of SRDs in children with sickle cell disease