Disseminated tuberculosis, CMV viraemia & haemophagocytic-lymphohistiocystosis syndrome in an adult patient with anti- IFNγ autoantibodies - case report and brief review.

We report a case of an adult female with disseminated tuberculosis, cytomegalovirus viraemia and haemophagocytic-lymphohistiocystosis syndrome associated with neutralizing anti- interferon gamma (IFNγ) autoantibodies demonstrated by absent IFNγ stimulated STAT1 phosphorylation in the presence of patient sera. A brief review of immunodeficiency caused by anti-IFNγ autoantibodies is also described.

Cryptococcal laryngitis in an immunocompetent asthmatic patient using inhaled corticosteroids.

We present a case of laryngeal cryptococcosis caused by cryptococcosis neoformans var. grubii affecting a patient using excessive inhaled corticosteroids. The patient experienced symptoms for several months prior to specialist review and the visualization of a mass lesion by nasopharyngoscopy. Fortunately a biopsy was performed and through histopathology & microbiological assessment a diagnosis of cryptococcal laryngitis was made. Treatment with 6 months of fluconazole resulted in clinical cure and resolution of symptoms. It is important to raise awareness of the risk of non-Candida fungal infections in patients on high dose corticosteroids, especially in the post covid era were steroids are more commonly prescribed.

Low-level parental mosaicism in an apparent de novo case of Peutz-Jeghers syndrome.

We report the case of a female found to have mosaicism for mutation in the STK11 gene, with the mutant allele expressed in her gametes, evident by her affected offspring, and in her gastrointestinal tract demonstrated on an excised polyp analysed for diagnosis. Mosaicism for Peutz-Jeghers syndrome (PJS) has been reported in a small number of cases previously but a clinical presentation such as this has not previously been described. This finding of mosaicism was several years after initial investigations failed to identify the same STK11 mutation in this woman whose son was diagnosed with PJS at a young age. This case highlights the importance of considering mosaicism as an explanation for apparent de novo cases of PJS syndrome. It also has implications for genetic counselling, predictive testing and cancer screening.

Genetic markers for detection of Escherichia coli K-12 harboring ampicillin-resistance plasmid from an industrial wastewater treatment effluent pond.

Biotechnology industries that use recombinant DNA technology are potential sources for release of genetically modified organisms to the environment. Antibiotic-resistance marker genes are commonly used for recombinant bacteria selection. One example is the marker gene coding for ß-lactamase (bla) in plasmids found in Escherichia coli K-12. The aim of this study was to provide an approach to develop a molecular method for genetic marker detection in E. coli K-12 harboring bla genes from an industrial wastewater treatment effluent pond (IWTEP). For the detection of bla and Achromobacter lyticus protease I (api) genes in samples from IWTEP, we employed multiplex polymerase chain reaction (PCR) using E. coli K-12 genetic marker detection primers, previously described in the literature, and primers designed in our laboratory. The microbiological screening method resulted in 22 bacterial colony-forming units isolated from three different IWTEP harvesting points. The multiplex PCR amplicons showed that five isolates were positive for the bla gene marker and negative for the E. coli K-12 and api genes. The 16S rRNA regions of positive microorganisms carrying the bla gene were genotyped by the MicroSeq®500 system. The bacteria found were Escherichia spp (3/5), Chromobacterium spp (1/5), and Aeromonas spp (1/5). None of the 22 isolated microorganisms presented the molecular pattern of E. coli K-12 harboring the bla gene. The presence of microorganisms positive for the bla gene and negative for E. coli K-12 harboring bla genes at IWTEP suggests that the ampicillin resistance found in the isolated bacteria could be from microorganisms other than the E. coli K-12 strain harboring plasmid.

Impairment of toll-like receptors 2 and 4 leads to compensatory mechanisms after sciatic nerve axotomy.

BACKGROUND: Peripheral nerve injury results in retrograde cell body-related changes in the spinal motoneurons that will contribute to the regenerative response of their axons. Successful functional recovery also depends on molecular events mediated by innate immune response during Wallerian degeneration in the nerve microenvironment. A previous study in our lab demonstrated that TLR 2 and 4 develop opposite effects on synaptic stability in the spinal cord after peripheral nerve injury. Therefore, we suggested that the better preservation of spinal cord microenvironment would positively influence distal axonal regrowth. In this context, the present work aimed to investigate the influence of TLR2 and TLR4 on regeneration and functional recovery after peripheral nerve injury. METHODS: Eighty-eight mice were anesthetized and subjected to unilateral sciatic nerve crush (C3H/HeJ, n = 22, C3H/HePas, n = 22; C57Bl6/J, n = 22 and TLR2(-/-), n = 22). After the appropriate survival times (3, 7, 14 days, and 5 weeks), all mice were killed and the sciatic nerves and tibialis cranialis muscles were processed for immunohistochemistry and transmission electron microscopy (TEM). Gait analysis, after sciatic nerve crushing, was performed in another set of mice (minimum of n = 8 per group), by using the walking track test (CatWalk system). RESULTS: TLR4 mutant mice presented greater functional recovery as well as an enhanced p75(NTR) and neurofilament protein expression as compared to the wild-type strain. Moreover, the better functional recovery in mutant mice was correlated to a greater number of nerve terminal sprouts. Knockout mice for TLR2 exhibited 30 % greater number of degenerated axons in the distal stump of the sciatic nerve and a decreased p75(NTR) and neurofilament protein expression compared to the wild type. However, the absence of TLR2 receptor did not influence the overall functional recovery. End-point equivalent functional recovery in transgenic mice may be a result of enhanced axonal diameter found at 2 weeks after lesion. CONCLUSIONS: Altogether, the present results indicate that the lack of TLR2 or the absence of functional TLR4 does affect the nerve regeneration process; however, such changes are minimized through different compensatory mechanisms, resulting in similar motor function recovery, as compared to wild-type mice. These findings contribute to the concept that innate immune-related molecules influence peripheral nerve regeneration by concurrently participating in processes taking place both at the CNS and PNS.

High-resolution photoelectron spectroscopy with angular selectivity - a tool to probe valence-Rydberg states and couplings in HCl(+).

Due to strong electron correlation effects and electron coupling with nuclear motion, the molecular inner-valence photoionization is still a challenge in electron spectroscopy, resulting in several interesting phenomena such as drastic changes of angular dependencies, spin-orbit induced predissociation, and complex interplay between adiabatic and nonadiabatic transitions. We investigated the excited electronic states of HCl(+) in the binding energy range 27.5-30.5 eV using synchrotron radiation based high-resolution inner-valence photoelectron spectroscopy with angular resolution and interpreted the observations with the help of ab initio calculations. Overlapping electronic states in this region were disentangled through the analysis of photoelectron emission anisotropies. For instance, a puzzling transition, which does not seem to obey either an adiabatic or a nonadiabatic picture, has been identified at ∼28.6 eV binding energy. By this study, we show that ultrahigh-resolution photoelectron spectroscopy with angular selectivity represents a powerful tool to probe the highly excited ionic molecular electronic states and their intricate couplings.

Case report: metachronous central nervous system desmoid tumours and thyroid carcinoma in a young familial adenomatous polyposis patient.

We report a familial adenomatous polyposis patient with a known truncating mutation on exon 15 of the APC gene who developed an invasive follicular thyroid cancer in addition to multiple intra-cranial and spinal desmoids. This combination of manifestations has not previously been recorded in the literature.

Arrabidaea chica extract improves gait recovery and changes collagen content during healing of the Achilles tendon.

INTRODUCTION: Tendon lesions are still a serious clinical problem. The leaves of the Bignoniaceae Arrabidaea chica (Humb. & Bonpl.) B. Verlot. (syn. Bignonia chica (Bonpl.)) have been used in traditional medicine and described in the literature for its healing properties. However, no study has shown the effects of A. chica during tendon healing. The aim of this study was to investigate the healing properties of the A. chica leaves extract on tendons after partial transection. METHODS: A partial transection in the tension region of the Achilles tendon of rats was performed with subsequent posterior topical application of A. chica extract (2.13g/mL in 0.85% saline solution) at the site of the injury. The animals (n=154) were separated into 7 groups: N - rats with tendons without transection; S7, S14 and S21 - rats with tendons treated with topical applications of saline for 7 days and sacrificed on the 7th, 14th and 21st days after surgery, respectively; A7, A14 and A21 - rats with tendons treated with topical applications of the plant extract. The transected regions of the tendons were analyzed through biochemical, morphological and functional analyses. To evaluate the type and concentration of collagen, Western blotting for collagen types I and III was performed, and the hydroxyproline concentration was determined. The participation of metalloproteinases (MMP)-2 and -9 during tendon remodelling was investigated through zymography. Gait recovery was analyzed using the catwalk system. The organization of the extracellular matrix and morphometry were detected in sections stained with haematoxylin-eosin. RESULTS: The application of A. chica extract in the region of tendon injury led to an increase in the amount of hydroxyproline (mg/g tissue) on the 7th (91.5±18.9) and 21st (95.8±11.9) days after the tendon lesion relative to the control groups treated with saline (S7: 75.2±7.2; and S21: 71.9±7.9). There were decreases in collagen types I and III (as determined by densitometry) in the groups treated with the plant extract 7 days after injury (type I: 103.9±15.9; type III: 206.3±8.1) compared to the saline-treated groups (type I: 165.2±31.1; type III: 338.6±48.8). The plant extract stimulated the synthesis of MMP-2 on the 21st day after the lesion and decreased the amount of latent and active isoforms of MMP-9 on the 14th day. Analysis by the catwalk system (max contact intensity) showed that the A. chica extract improved the gait of rats on the 7th day of the healing process when compared to the saline group. CONCLUSIONS: The use of A. chica extract during the healing process of the tendon leads to an increase in collagen content and improved gait recovery. Further studies will be performed to analyze the effect of this plant extract on the organization of the collagen bundles of tendons after lesions and to study its probable anti-inflammatory effect.

Alpha motoneurone input changes in dystrophic MDX mice after sciatic nerve transection.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy. At present, a lot is known about the muscular degeneration in DMD, but few studies have focused on the effects on the central nervous system. In this sense, retrograde changes in the microenvironment around motor neurones in the spinal cord may contribute to the pathogenesis of the dystrophinopathies. AIMS: The aim of this study was to investigate synaptic alterations and glial reactivity in the microenvironment close to spinal motor neurones in a DMD animal model. METHODS: Six-week-old male MDX mice were subjected to left sciatic nerve transection. The axotomy was performed after the muscular degeneration/regeneration cycles previously described in such animal models. C57BL/10 mice were used as the control. Seven days after surgery, the animals were sacrificed and the lumbar spinal cords processed for immunohistochemistry using antibodies to the major histocompatibility complex of class I (MHC I), synaptophysin, IBA-1 and glial fibrillary acidic protein (GFAP). RESULTS: MHC I expression increased in both strains after axotomy. Nevertheless, the MDX mice displayed significantly lower MHC I up-regulation. With respect to GFAP expression, the MDX mice showed greater astrogliosis as compared with C57BL/10 mice. The MDX mice displayed a significant decrease in synaptophysin expression. Indeed, the ultrastructural quantitative analysis showed more intense synaptic detachment in MDX mice, indicating a reduction in synaptic activity before and after axotomy. CONCLUSIONS: The reduction in active inputs and increased gliosis in MDX mice may be associated with the muscle degeneration/regeneration cycles that occur postnatally, and could contribute to the seriousness of the disease.

Identificação do limiar anaeróbio em indivíduos com diabetes tipo-2 sedentários e fisicamente ativos / Identification of the anaerobic threshold in sedentary and physically active individuals with type 2 diabetes

OBJETIVO: Comparar intensidades de limiar anaeróbio (LA) obtidas a partir do lactato, ventilação e glicemia em diabéticos tipo-2 ativos (DA) e sedentários (DS) e não-diabéticos ativos (NDA), e correlacionar variáveis metabólicas, hemodinâmicas e de composição corporal com o LA. METODOLOGIA: Grupos de DS (n= 09, 56,7 ± 11,9 anos), DA (n= 09, 50,6 ± 12,7 anos) e NDA (n= 10, 48,1 ± 10,8 anos) foram submetidos a um teste em cicloergômetro com incrementos de 15W até a exaustão. Freqüência cardíaca, pressão arterial (PA), percepção de esforço, lactato, glicemia e variáveis ventilatórias foram mensuradas nos 20seg finais de cada estágio de 3min para determinação dos limiares de lactato, ventilatório e glicêmico. RESULTADOS: As intensidades associadas ao LA identificado pelos diferentes métodos não diferiram entre si (p> 0,05). As intensidades absolutas foram menores para o grupo DS em relação aos grupos ativos (p< 0,05), não sendo observadas diferenças entre os grupos para as intensidades relativas ao consumo máximo de oxigênio ( por centoVO2 pico) e potência máxima ( por centoPpico) de ocorrência do LA. Observou-se correlação significativa entre LA e o percentual de gordura (r= -0,52), com tendência à correlação entre o LA e a glicemia ambulatorial (r= -0,33). Variáveis hemodinâmicas e LA não demonstraram correlações. CONCLUSÃO: O LA foi identificado a partir das técnicas estudadas em diabéticos tipo-2 e não-diabéticos. Apesar das diferenças entre grupos para as intensidades absolutas (Watts), a patologia pareceu não influenciar as intensidades relativas em que o LA foi observado. O LA apresentou correlação com a composição corporal e tendência a se correlacionar com a glicemia ambulatorial, sugerindo-se, com isso, o LA como um parâmetro importante na avaliação clínica destes pacientes.

OBJECTIVE: To compare anaerobic threshold (AT) intensities determined from blood lactate, blood glucose and ventilatory responses among sedentary (SD) and physically active (AD) type-2 diabetics and active non-diabetics (AND), and to correlate metabolic, hemodynamic and body composition variables with the AT. METHOD: The SD (n= 9, 56.7 ± 11.9 years), AD (n= 9, 50.6 ± 12.7 years) and AND (n= 10, 48.1 ± 10.8 years) groups performed a cycle ergometer test with increases of 15 watts every three minutes until exhaustion. Heart rate, arterial pressure, perceived exertion, blood lactate, blood glucose and ventilatory variables were measured during the last 20 seconds of each incremental stage, to determine the lactate, ventilatory and glucose thresholds. RESULTS: The AT intensities identified by the different methods did not differ from each other (p> 0.05). However, the absolute intensities were lower for SD than for the active groups (p< 0.05). No differences in intensity were found between the groups in relation to maximum oxygen consumption ( percentVO2 peak) and maximum power ( percentPpeak) at which the AT was observed. There was a significant correlation between AT and percentage fat (r= -0.52), and there was a trend towards correlation between AT and ambulatory blood glucose (r= -0.33). The hemodynamic variables did not show any correlations with AT. CONCLUSION: The AT was identified by means of the techniques studied, among type 2 diabetics and non-diabetics. Despite the differences between the groups with regard to absolute intensities (watts), diabetes did not appear to influence the relative intensities at which the AT was observed. The AT presented a correlation with body composition and a trend towards correlation with ambulatory blood glucose, thus suggesting that the AT is an important parameter in clinical assessments for such patients.

Effect of xylitol:sorbitol on fluoride enamel demineralization reduction in situ.

OBJECTIVES: To evaluate if sugar alcohols would reduce enamel demineralization enhancing the fluoride (F) effect. METHODS: A crossover in situ study was conducted in four phases, during which 10 volunteers were submitted to one of the treatments: (I) Distilled and deionized water, as a negative control; (II) F (226 microg F/ml as NaF; concentration used in commercial mouthrinse); (III) X:S (xylitol:sorbitol 1:3; final concentration 1.6M; 28% of sugar alcohols) and (IV) F+X:S (same final concentration that groups II and III). The volunteers wore palatal appliances containing four bovine enamel blocks of known surface microhardness (SMH), covered with a 'test plaque' of mutans streptococci, which were immersed during 1 min in one of the allocated treatment solutions simultaneously that the volunteers rinsed their mouths with the same solution. After the rinsing the appliances were put in the mouth and after 20 min a cariogenic challenge was made with 20% sucrose solution during 1 min. After further 45 min the 'test plaque' was collected for F analysis, enamel SMH was again determined and the percentage of change in relation to baseline was calculated; F uptake in enamel was also determined. RESULTS: With respect to all the analyses made, the group F+X:S did not differ from the F treatment (p>0.05) and the groups treated with F and F+X:S differed from the negative control (p<0.05). CONCLUSIONS: The results suggest that xylitol:sorbitol may not enhance the effect of fluoride present in mouth rinse on the reduction of enamel demineralization.

Effect of a calcium carbonate-based dentifrice on in situ enamel remineralization.

This crossover study evaluated the effect of calcium carbonate (CaCO(3))-based monofluorophosphate dentifrice on enamel remineralization. Ten volunteers wore palatal appliances containing four enamel blocks with caries-like lesions, two of them covered by a test plaque of mutans streptococci. The following treatments were evaluated: a negative control, a silica-based or a CaCO(3)-based dentifrice, and the percentage of enamel surface microhardness recovery was determined. The CaCO(3)-based dentifrice was more effective than the negative control on the enhancement of enamel remineralization, either in the presence or absence of test plaque. This efficacy was also shown by the silica-based dentifrice but only in the presence of test plaque.

Effect of a calcium carbonate-based dentifrice on enamel demineralization in situ.

Since the effect of calcium carbonate (CaCO(3)) based dentifrice on enamel demineralization is not clearly established, it was evaluated using the IEDT model described by Zero's group in 1992. This study had a crossover design and 10 volunteers were submitted to 3 treatment groups: a negative control, brushing without dentifrice; an active control, brushing with silica-based dentifrice (SiO(2)/MFP group), and the experimental group, brushing with CaCO(3)-based dentifrice (CaCO(3)/MFP). Both dentifrices contained 1,500 microgram F/g (w/w) as sodium monofluorophosphate (MFP). Enamel surface microhardness was determined in the dental blocks and the percentage change in relation to baseline was calculated. Fluoride uptake in enamel and its concentration in 'test plaque' were determined. The results showed that the dentifrice containing CaCO(3)/MFP was more effective than SiO(2)/MFP in reducing enamel demineralization (p < 0.05). A higher concentration of fluoride ion was found in 'test plaque' treated with CaCO(3)/MFP than in the negative control (p < 0.05). The results suggest that CaCO(3) abrasive may enhance the effect of fluoride present in dentifrice on dental caries control.

Headspace gas chromatographic determination of 1,3-butadiene in simulated saliva.

A headspace gas chromatographic (GC) method was developed to determine 1,3-butadiene (1,3-BD) in simulated saliva in contact with chewing gum. The calibration graph was linear, and the limit of detection was 0.004 mg/L, which is well below the migration limit for this substance. The headspace GC method provides rapid and reliable analysis for monitoring 1,3-BD migration from chewing gum into simulated saliva. In this paper, we report headspace methodology for sensitive determination of 1,3-BD in chewing gum and results of selected analyses, enabling preliminary assessment of possible exposure to 1,3-BD through migration.

[Plasmapheresis in Landry-Guillain-Barré-Strohl syndrome with or rapidly appearing respiratory insufficiency]. / Plasmaferese na síndrome de Landry-Guillain-Barré-Strohl com insuficiência ventilatória ou rapidamente ascendente.

The authors report three cases of Landry-Guillain-Barré-Strohl syndrome successfully treated by plasma exchange--the only cases in the Brazilian State of Rio Grande do Sul. The authors go through a brief literature revision and discuss more thoroughly the plasma exchange procedure, establishing criteria for its indication.