Reduction of cPLA2alpha overexpression: an efficient anti-inflammatory therapy for collagen-induced arthritis

Cytosolic phospholipase A2alpha (cPLA2) plays an important role in the development of several inflammatory diseases. The aim of the present study is to determine whether inhibition of cPLA2 expression, using specific antisense oligonucleotides against cPLA2 (antisense), is efficient in reducing inflammation after its development. Two mouse models of inflammation were included in the study: thioglicolate peritonitis and collagen-induced arthritis (CIA). The antisense was found to be specific and efficient in inhibiting cPLA2 expression and NADPH oxidase activity ex vivo in peritoneal phagocytes. Immunoblotting and immunohistochemistry analysis showed a significant elevation in cPLA2 expression in the inflamed joints of collagen-induced arthritis mice localized in cell infiltrate, chondrocytes and the surrounding skin and skeletal muscle. Similarly, the cPLA2 metabolite, leukotriene B4, accumulated in the peritoneal cavity of mice with peritonitis. Inhibition of elevated cPLA2 expression after development of inflammation by intravenous administration of antisense resulted in a dramatic reduction in inflammation and a significant reduction in neutrophils recruitment to the site of inflammation in both mouse models of inflammation. Our results demonstrate the critical role of cPLA2 for the duration of inflammation and suggest that inhibition of cPLA2 expression by antisense oligonucleotides may serve as an efficient treatment of inflammatory diseases.     

Imaging of lower extremity stress fracture injuries

Stress reactions and stress fractures in the lower extremities occur frequently in military and athletic populations. As the clinical symptoms of stress fracture may mimic other less severe musculoskeletal injuries, the diagnosis of stress fracture can often be delayed. The following article reviews the characteristics, advantages and disadvantages of the various imaging tools available to detect stress fracture of the lower limbs in order to clarify their utility when diagnosing this condition. Plain radiography, the primary imaging tool for diagnosing suspected stress injuries, may not detect stress fracture injury until fracture healing is well underway. In some cases of suspected stress fracture, this delay in diagnosis can lead to catastrophic fracture and surgical intervention. Bone scintigraphy has long been recommended for the diagnosis of stress fracture, claiming that skeletal scintigraphy is 100% sensitive for the detection of stress fracture. However, there is a potential for a false negative examination and findings might be nonspecific as tumours or infections may mimic stress injury. In addition, bone scintigraphy involves ionizing radiation and it should not be used whenever there is an alternative. Computed tomography (CT) provides exquisitely fine osseous detail, but should be reserved only for specific indications because it also involves ionizing radiation. Magnetic resonance (MR) imaging, which is noninvasive, has no ionizing radiation, is more rapidly performed than bone scintigraphy, and should be the method of choice for stress fracture diagnosis whenever it is available. However, using MR imaging demands an experienced diagnostician in order to decrease reported false-positive injuries. The ultrasonography technique, which is being used increasingly in the evaluation of the musculoskeletal system has recently been shown to have some potential in the diagnosis of stress fracture; however, currently the imaging modalities are insufficient. The peripheral quantitative CT (pQCT) device, which has been developed to specifically assess skeletal status of the extremities, provides data on bone geometry, strength and density. However, the pQCT needs further evaluation prior to being considered for use in diagnosis stress changes in bone. This article reviews the utility of each of the imaging modalities currently available to detect stress fracture injuries of the lower extremities, as well as other utilization factors, which include exposure to ionizing radiation, the ability to detect early- and late-stage reactions in the bone and surrounding soft tissues, and the ability to differentiate between different types of bone lesions.     

An Evaluation of the Effects of Photobiomodulation Therapy on the Peri-Implant Bone Healing of Implants with Different Surfaces: An In Vivo Study

(1) Background: This study evaluates the effects of photobiomodulation (PBM) therapy on the peri-implant bone healing of implants with a machined surface (MS) and treated surface (TS). (2) Methods: Topographic characterization of the surfaces (scanning electron microscopy [SEM]- energy dispersive X-ray spectroscopy [EDX]) was performed before and after implant removal. Twenty rabbits were randomly divided into four groups: MS and TS groups (without PBM therapy) and LMS and LTS groups (with PBM therapy). After implant placement, the stability coefficient (ISQ) was measured. In the periods of 21 and 42 days, the ISQ was measured again, followed by biomechanical analysis. (3) Results: The surfaces of the TS implants showed topographic differences compared with MS implants. The ISQ values of the LMS were statistically significant when compared with those of the MS at 42 days (p < 0.001). The removal torque values of the LMS were statistically significant when compared with those of the MS at 21 days (p = 0.023) and 42 days (p = 0.023). For SEM, in general, the LMS, TS and LTS presented high bone tissue coverage when compared to MS. (4) Conclusions: The PBM therapy modulated the osseointegration process and was evidenced mainly on the machined surface.     

Transepidermal water loss and skin hydration in preterm infants during phototherapy.

TEWL and skin hydration was measured in 7 body areas before and during phototherapy in 31 preterm infants (gestational age 25 to 36 weeks). Each patient served as his/her own control. There was a mean increase of 26.4% in TEWL during phototherapy. Most prominent increases were recorded in the cubital fossa (45.9%), groin (36.4%), and back (29%). There were no significant differences in stratum corneum moisture in six of the seven body areas before and during phototherapy. This study provides a better understanding of skin physiology during phototherapy in preterm infants and has important implications for the estimation of fluid replacement.     

Pharmacokinetic Analysis of the Structural Requirements for Forming “Stable” Analogues of Valpromide

The following valpromide (VPD) analogues were synthesized and their structure-pharmacokinetic relationships explored: 3-ethyl pentanamide (EPD), methylneopentylacetamide (MND), 1-methyl cyclohexanecarboxamide (MCD), cycloheptanecarboxamide (CHD), and t-butylacetamide (TBD). Two aliphatic (EPD and MND) and two cyclic amides (MCD and CHD) underwent complete or partial conversion to their corresponding acids. The only amide found in this study to be stable to the amide-acid biotransformation was TBD. It also had the lowest clearance and the longest half-life and mean residence time. Unlike the other investigated amides, TBD contained two substitutions of two methyl moieties at the position of its chemical structure. A stable valpromide analogue must have either two substitutions at the position, such as in the case of TBD, or a substitution in the and positions, such as in the case of the VPD isomer valnoctamide (VCD). This paper discusses the antiepileptic potential of stable VPD analogues which may be more potent and less teratogenic than their biotransformed isomers.     

Spectrophotometric and liquid chromatographic determination of fenofibrate and vinpocetine and their hydrolysis products

Several spectrophotometric and HPLC methods are presented for the determination of fenofibrate, vinpocetine and their hydrolysis products. The resolution of either fenofibrate or vinpocetine and their hydrolysis products has been accomplished by using numerical spectrophotometric methods as partial least squares (PLS-1) and principal component regression (PCR) applied to UV spectra; and graphical spectrophotometric methods as first derivative of ratio spectra (1DD) or first (1D) and second (2D) derivative spectrophotometry for vinpocetine and fenofibrate, respectively. In addition HPLC methods were developed using ODS column with mobile phase consisting of acetonitrile-water (80:20, v/v, pH 4) with UV detection at 287 nm for fenofibrate and a mobile phase consisting of acetonitrile-10 mM KH2PO4, containing 0.1% diethylamine (60:40, v/v, pH 4.6) with UV detection at 270 nm for vinpocetine. The proposed methods were successfully applied for the determination of each drug and its hydrolysis product in laboratory-prepared mixture and pharmaceutical preparation. The proposed HPLC and derivative spectrophotometric methods were used to investigate the kinetics of acidic and alkaline hydrolytic processes of each drug. The pH-rate profile of hydrolysis of each drug in Britton-Robinson buffer solutions was studied.     

Metástasis en la mama,un diagnóstico infrecuente. ¿Qué deben saber los radiólogos?

ObjectiveTo analyze the imaging characteristics of histologically diagnosed metastases to the breast.Material and methodsWe selected patients histologically diagnosed with metastases to the breast in our diagnostic and interventional breast imaging unit between March 2010 and September 2018.ResultsA total of 9 patients (all women; mean age, 60 y; age range, 28–89 y) were diagnosed with metastases to the breast. In 1 (11.11%) case, the primary disease was diagnosed from the breast lesion. The primary tumors were melanoma (n = 5), neuroendocrine tumor (n = 2, one from the small bowel and one from the cervix), lung adenocarcinoma (n = 1), and ovarian cancer (n = 1). The clinical and imaging manifestations depend on the type of dissemination of disease and can simulate benign and malignant primary breast lesions.ConclusionThere is no specific imaging pattern for metastases to the breast that would help to orient the diagnosis. It is important to consider this etiological possibility if the patient has a history of a primary tumor in another organ.     

A Chlamydia trachomatis 23S rRNA G1523A variant escaping detection in the Aptima Combo 2 assay (Hologic) was widespread across Denmark in July–September 2019

Chlamydia trachomatis infection is the most common bacterial sexually transmitted infection globally, and nucleic acid amplification tests (NAATs) are recommended for highly sensitive and specific diagnosis. In early 2019, the Finnish new variant of Chlamydia trachomatis (FI-nvCT) was identified. The FI-nvCT has a C1515T mutation in the 23S rRNA gene, making it escaping detection in the Aptima Combo 2 (AC2; Hologic) NAAT, and the FI-nvCT has been subsequently reported in Sweden and Norway. In the present study, we investigated the presence of the FI-nvCT and other AC2 diagnostic-escape CT mutants in July–September 2019 in Denmark. The FI-nvCT was present but rare in Denmark. However, another AC2 diagnostic-escape CT mutant (with a 23S rRNA G1523A mutation) was found to be widespread across Denmark, accounting for 95% (76/80) of AC2 diagnostic-escape nvCT samples from five Danish CT-diagnostic laboratories. This nvCT-G1523A has previously only been detected in one single sample in the United Kingdom and Norway, respectively. It is vital to monitor the continued stability of the NAAT targets in local, national and international settings and monitor as well as appropriately analyse incidence, unexplained shifts in diagnostics rates and/or annual collections of samples diagnosed as negative/equivocal using NAATs with different target(s). Furthermore, diagnostic CT NAATs with dual target sequences are crucial, and fortunately, an updated Hologic AC2 assay including one additional target sequence is in advanced development.     

Altered Spinal Excitability in Patients with Primary Fibromyalgia: A Case-Control Study

Background and PurposeAbnormal excitability of the central nervous system, both spinal and supraspinal, has previously been described as a pathophysiological plastic mechanism for chronic pain syndromes. Primary fibromyalgia (FM) as one extreme of this spectrum of diseases. This case-control study aimed to determine the changes in the spinal excitability by investigating the Hoffman reflex (H-reflex) in patients with FM.MethodsThirty-eight patients with FM and 30 healthy controls participated in this case-control study. We measured the H-reflex bilaterally in the upper limbs (flexor carpi radialis) and the lower limbs (gastrocnemius and soleus). Moreover, pain-related variables were measured, including pain severity (using a visual analogue scale), pain duration, Widespread Pain Index, and the score on the Symptom Severity Scale. Various psychiatric comorbidities and quality-of-life parameters were measured for each patient, including scores on the Hamilton Depression Rating Scale, Taylor''s Manifest Anxiety Scale, and the Revised Fibromyalgia Impact Questionnaire.ResultsA significant increase in the ratio of the maximum baseline-to-peak amplitudes of H and M waves (H_max/M_max) but not in the H-wave minimum latency was found in patients with FM compared with healthy controls. There were no significant correlations between this ratio in both muscles and the various pain-related measures, psychiatric comorbidity, and quality of life in patients with FM. Patients with FM suffered more depression and anxiety than did the controls.ConclusionsWe found increased spinal excitability in patients with FM, which was not confined to the site of maximum pain. This information may help in the diagnosis of FM and supports the hypothesis of central sensitization.