Interleukin newcomers creating new numbers in rheumatology: IL-34 to IL-38

The development of innovative technologies is steadily increasing the body of knowledge on molecules involved in physiological functions. Thus, several interleukins (ILs) have been identified and characterized in the past few years. Here, we detail the structural and functional characteristics of IL-34 to IL-38 with special attention to their involvement in inflammatory joint disease. IL-34 chiefly increases osteoclast activation and proliferation and therefore, it plays a direct role in bone destruction as seen in rheumatoid arthritis (RA). Regulatory T-cells (Tregs) express IL-35, which therefore exerts anti-inflammatory effects by restoring Treg suppressive capabilities and by inhibiting the Th17 pathway. IL-37 has anti-inflammatory effects mediated by a negative feedback loop that decreases the release of pro-inflammatory cytokines. IL-36 belongs to the IL-1 family and has three different forms. Although this cytokine has been chiefly studied in psoriasis and psoriatic arthritis, it also exerts pro-inflammatory effects in RA. The specific IL-36 antagonist, IL-36Ra binds to the IL-36 receptor, thereby, preventing signal transduction. Finally, IL-38 is a recently identified cytokine whose effect may resemble that of IL-36Ra as it binds to the IL-36 receptor and inhibits its effects, particularly the Th17-response. Although the exact roles for these cytokines awaits elucidation, the current improvements in our knowledge of the mechanisms that regulate chronic inflammatory conditions, such as RA may lead to the identification of new treatment targets.     

Impaired fasting glucose: Pro-diabetic, “atheroprotective” and modified by metabolic syndrome

AIM: To investigate whether impaired fasting glucose (IFG) confers cardiovascular risk.METHODS: A non-diabetic population-based sample representative of middle-aged and elderly Turks was studied at 8.5 years’ follow-up for incident diabetes and coronary heart disease (CHD). Metabolic syndrome (MetS) was defined by ATP-III criteria modified for male abdominal obesity, and IFG and type 2 diabetes were identified by criteria of the American Diabetes Association. Stratification by presence of MetS was used. Outcomes were predicted providing estimates for hazard ratio (HR) obtained by use of Cox proportional hazards regression analysis in models that controlled for potential confounders.RESULTS: In 3181 adults (aged 52 ± 11.5 years at baseline), analysis stratified by MetS, gender and IFG status distinguished normoglycemic subjects by a “hypertriglyceridemic waist” phenotype consisting of significantly higher waist circumference, fasting triglyceride and lower high-density lipoprotein-cholesterol, regardless of gender and MetS. Additionally, lipoprotein (Lp) (a) tended to be lower in (especially female) participants with MetS. Multivariable linear regression in a subset of the sample demonstrated decreased Lp (a) levels to be associated with increased fasting glucose and insulin concentrations, again particularly in women. In Cox regression analysis, compared with normoglycemia, baseline IFG adjusted for major confounders significantly predicted incident diabetes at a 3-fold HR in men and only women with MetS. Cox models for developing CHD in 339 individuals, adjusted for conventional risk factors, revealed that IFG status protected against CHD risk [HR = 0.37 (95%CI: 0.14-0.998)] in subjects free of MetS, a protection that attenuated partly in male and fully in female participants with MetS.CONCLUSION: IFG status in non-diabetic people without MetS displays reduced future CHD risk, yet is modulated by MetS, likely due to autoimmune activation linked to serum Lp (a).     

Common genetic coagulation variants are not associated with ischemic stroke in a case-control study

Abstract

Objective: Abnormalities in the coagulation pathway are often included in the diagnostic work-up of stroke patients, especially in young adults with cryptogenic stroke.

Methods: Three common genetic variants within the coagulation cascade were investigated in 500 control subjects and in 167 patients with ischemic stroke defined by TOAST subclassification. Analysed variants were factor V Leiden, prothrombin 20210G→A and factor XIII Val34Leu.

Results: The factor V Leiden mutation was over-represented in patients with cardioembolic stroke for trend, whereas the prothrombin 20210G→A variant and the factor XIII polymorphism Val34Leu were not associated with stroke of any subtype. The three polymorphisms showed no association with stroke in subgroups of patients defined by age (<40, 40–49, 50–59, ≥60 years).

Discussion: This study suggests that the analysis of prothrombin 20210G→A and factor XIII Val34Leu is not a useful diagnostic procedure in the work-up of ischemic stroke.     

Blefarospasmo y espasmo hemifacial: tratamiento a largo plazo con toxina botulínica

Introduction

Our purpose is to describe the demographic, clinical and therapeutic characteristics of patients with blepharospasm (BS) and hemifacial spasm (HFS) in treatment with botulinum toxin type A (BtA).

Patients and methods

Retrospective analysis of patients diagnosed with BS or HFS and treated with BtA in the Neurology Department at Complejo Asistencial de Segovia between March 1991 and December 2009.

Results

Different variables were collected from 34 patients with BS and 55 with HFS, of whom 44.1% and 32.7% respectively had been undergoing treatment with BtA for more than 10 years. Elapsed time from symptom onset to the first visit was 24 months in the BS group and 59.7 months in the HFS group. Diagnosis was given on the first visit for 76.5% of the BS patients and 90.7% of the HFS patients. Patients were referred by their primary care centres in 34.6% of the cases with BS and in 77.6% of the cases with HFS. The most commonly used BtA preparation was BOTOX^® in both groups, and there were no cases of primary or secondary resistance. The median dose of BtA was raised gradually in both groups, and the increase was statistically significant during the early years of treatment. The most common side effect was ptosis (47.1% in BS, 32.5% in HFS).

Conclusions

BS and HFS are the most common facial movement disorders. The demographic and clinical characteristics and therapeutic findings from this study show that treatment with BtA is both effective and safe over the long term.     

Relevancia del efecto de posición serial en el diagnóstico diferencial entre el deterioro cognitivo leve,la demencia de tipo Alzheimer y el envejecimiento normal

Serial position effects are observed when a person memorises a series of words exceeding his or her attention span. Cognitively normal individuals recall words at the beginning and end of the list more frequently than those in the middle, which reflects the way that short- and long-term episodic memory works.     

Resultados quirúrgicos a largo plazo en pacientes con epilepsia fármaco-resistente del lóbulo temporal sin anormalidades histológicas

Introduction

Reports on surgical outcomes in patients with drug-resistant temporal lobe epilepsy without histological abnormalities are scarce.

Methods

Retrospective review of data from patients with drug-resistant temporal lobe epilepsy and no histopathological alterations who underwent anterior mesial temporal lobectomy. We analysed the following variables: age, sex, age at seizure onset, age at surgery, time elapsed between diagnosis and the date of the surgery, follow-up time, and classification according to the Engel rating scale.

Results

From a database of 256 temporal lobectomies, 21 were identified as meeting the inclusion criteria. The average age upon diagnosis of epilepsy was 8.3 years and average age at time of surgery was 28.6 years. The mean time elapsed between diagnosis and surgery was 20.2 years. After a mean follow-up of 6.5 years, 90.5% of the patients showed favourable outcomes (classes i and ii) and 42.9% were seizure-free (class IA). Comparative analysis of the variables revealed that average age at seizure onset was the only statistically significant difference between groups, with age at onset being lower in patients with favourable outcomes.

Conclusion

Although long-term surgical outcomes were favourable for a large majority of patients, the percentage of seizure-free patients is lower than in patients with lesional epilepsy and comparable to that previously reported in the literature.     

Syntenin‐a promotes spinal cord regeneration following injury in adult zebrafish

In contrast to mammals, adult zebrafish recover locomotor function after spinal cord injury, in part due to the capacity of the central nervous system to repair severed connections. To identify molecular cues that underlie regeneration, we conducted mRNA expression profiling and found that syntenin‐a expression is upregulated in the adult zebrafish spinal cord caudal to the lesion site after injury. Syntenin is a scaffolding protein involved in mammalian cell adhesion and movement, axonal outgrowth, establishment of cell polarity, and protein trafficking. It could thus be expected to be involved in supporting regeneration in fish. Syntenin‐a mRNA and protein are expressed in neurons, glia and newly generated neural cells, and upregulated caudal to the lesion site on days 6 and 11 following spinal cord injury. Treatment of spinal cord‐injured fish with two different antisense morpholinos to knock down syntenin‐a expression resulted in significant inhibition of locomotor recovery at 5 and 6 weeks after injury, when compared to control morpholino‐treated fish. Knock‐down of syntenin‐a reduced regrowth of descending axons from brainstem neurons into the spinal cord caudal to the lesion site. These observations indicate that syntenin‐a is involved in regeneration after traumatic insult to the central nervous system of adult zebrafish, potentially leading to novel insights into the cellular and molecular mechanisms that require activation in the regeneration‐deficient mammalian central nervous system.     

Validation of micro-CT against the section method regarding the assessment of marginal leakage of sealants

Background: The aim of this study was to validate the micro‐CT and related software against the section method using the stereomicroscope for marginal leakage assessment along the sealant‐enamel interface. Methods: Pits and fissures of the occlusal surface of 10 teeth were sealed with a resin‐fissure sealant material without acid etching, thermocycled for 5000 cycles, immersed in 50% silver nitrate for three hours and scanned using micro‐CT. Teeth were embedded in epoxy resin and cut in three sections. The middle section was subjected to micro‐CT and stereomicroscopy. Images were taken from the left and right sides of the sealant‐enamel interface at both the left and the right site of the section. Two experienced evaluators assessed marginal leakage. Results: Both assessment instruments observed no leakage in 37 out of the 40 images evaluated. Leakage at the sealant‐enamel interface was observed in three stereomicroscopy images only. A fracture line in the sealant was seen on eight stereomicroscopy images and observed in only two micro‐CT images. Conclusions: The quality of the micro‐CT and related software used in the present study does not qualify it to replace the section method as the gold standard for marginal leakage assessment at the sealant‐enamel interface of permanent teeth.