[Sensitivity of the sympathetic skin response and scintigraphy in the diagnosis of complex regional pain syndrome]. / Sensibilidad de la respuesta simpática cutánea y de la gammagrafía en el diagnóstico del síndrome dolor regional complejo.

OBJECTIVE: To evaluate the sensitivity of sympathetic skin response (SSR) and compare it with scintigraphy in patients with complex regional pain syndrome diagnosed according to the Budapest criteria. MATERIAL AND METHODS: Twenty-two patients with complex regional pain syndrome who attended the Rehabilitation and Physical Medicine Department between January-2018 and May-2022 have been prospectively evaluated. The scintigraphy was considered positive if in the 1st-2nd phase slight asymmetric and diffuse uptake was observed, or when in the 3rd phase marked periarticular radioisotope uptake was observed. SSR was abnormal if: a) no response after 20 stimuli; b) lack of habituation with permanence of the stimuli greater than 67.2%. RESULTS: Age 55.4±8.57 years. Complex regional pain syndrome was more frequent in women (90.9%), more common in upper limbs (68.2%) than lower limbs (31.8%). In SSR, we have observed normal response (<67.2%) in 2 patients (11.1%), lack of SSR in 2 patients (11.1%) and lack of habituation (>67.2%) in 14 patients (77.8%). In total, 16 patients presented abnormal or absent responses (88.8%). The diagnostic sensitivity of scintigraphy is similar to that of SSR (89.5% vs 88.8%), with no statistical difference (P=.6721). CONCLUSION: Scintigraphy has shown similar sensitivity to SSR, although the simplicity, security, low cost, non-ionizing and non-invasiveness of the latter technique suggest that it could be more cost-effective. The lack of habituation and the absence of response could identify response patterns and localize the involvement in the afferent, central, efferent or post-ganglionic pathways.

Expression profiling of breast tumors based on human epidermal growth factor receptor 2 status defines migration-related genes.

OBJECTIVE: Breast cancer is a heterogeneous neoplasm. Distinct subtypes of breast cancer have been defined, suggesting the existence of molecular differences contributing to their clinical outcomes. However, the molecular differences between human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative breast cancer tumors remain unclear. The aim of this study was to identify a gene expression profile for breast tumors based on their HER2 status. METHODS: The HER2 status was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in 54 breast tumor samples. Using Affymetrix microarray data from these breast tumors, we established the expression profiling of breast cancer based on HER2 IHC and FISH results. To validate microarray experiment data, real-time quantitative reverse transcription-PCR was performed. RESULTS: We found significant differences between the HER2-positive and HER2-negative breast tumor samples, which included overexpression of HER2, other genes located on 17q12 and genes functionally related to migration. CONCLUSION: Our study shows the potential of integrated genomic profiling to shed light on the molecular knowledge of HER2-positive breast tumors.

[Calcification of the medial collateral ligament of the knee: Rehabilitative management with radial electro shock wave therapy plus iontophoresis of a rare entity. Clinical case and review]. / Calcificación del ligamento colateral medial de la rodilla: manejo rehabilitador con ondas de choque más iontoforesis de una entidad poco frecuente. Caso clínico y revisión.

The medial collateral ligament (MCL) of the knee is a commonly injured ligament structure. Calcification of the MCL is very infrequent, benign, related to metabolic disorders and is a consequence of the deposition of calcium hydroxyapatite in the periarticular region. The clinical, histological and radiological picture of calcific tendonitis is defined and the etiology is multifactorial. Treatment is initially conservative and if it fails, interventionist; surgery being the last therapeutic step. There are very few reports in the literature, with only 10 cases/case series published. It is important to differentiate it from the Pellegrini-Stieda sign and/or syndrome, where the traumatic history is essential to diagnose it. The clinical case is that of a 64-year-old woman in whom we present the treatment of calcification of the MCL using radial electro shock wave therapy plus iontophoresis, we report the effectiveness of the treatment in the management of pain and calcification, and we carry out a brief review on the subject.

[Transcutaneous stimulation of the posterior tibial nerve modifies the sympathetic skin response and improves overactive bladder syndrome: Case series and possible diagnostic test]. / La estimulación transcutánea del nervio tibial posterior modifica la respuesta simpática cutánea y mejora el síndrome de vejiga hiperactiva: serie de casos y posible prueba diagnóstica.

OBJECTIVE: (a) To assess the effect of transcutaneous neuromodulation (TNM) of the posterior tibial nerve plus biofeedback on the sympathetic skin response (SSR). (b) Evaluate its effect on clinical symptoms. (c) Consider SSR as a probable neurophysiological test useful both for diagnosis and for follow-up in patients with overactive bladder (OAB). (d) Evaluate its cost compared to other techniques. MATERIAL AND METHODS: A prospective quasi-experimental before and after study in 10 OAB patients. OUTCOME VARIABLES: daytime (DUF) and nighttime (NUF) urinary frequency, strength of the pelvic floor muscles measured by manometry (maximum and mean pressure) and sympathetic skin response (SSR). RESULTS: DUF improved from 10.3±5.45 to 5.9±2.42 episodes (P=.0050). The NUF improved from 2.4±1.5 to 0.6±0.69 episodes (P=.0012). The maximum pressure ranged from 34.7±16.51 to 39.7±3.65mmHg (P=.0195). The mean pressure of the pelvic floor muscles improved from 6.6±3.65 to 9.3±5.43mmHg (P=.0333). SSR changed from 100% hyperexcitability prior to treatment to 50±14.14% (P=.0000). CONCLUSION: TNM plus biofeedback could modify SSR and improve clinical and manometry variables in a series of patients with OAB. The probable diagnostic and prognostic utility of this neurophysiological test in OAB and detrusor hyperactivity is reported for the first time. A larger sample study is needed to confirm the promising findings seen in this preliminary study.

Real-time RT-PCR analysis for evaluating the Her2/neu status in breast cancer.

OBJECTIVE: The Her2/neu status is of great clinical value in breast tumor patients. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) techniques are the test of choice for many practicing pathologies. The main objective of this retrospective study was to investigate the relationship between Her2/neu breast cancer amplification and overexpression (DNA, mRNA and protein). METHODS: To accomplish this goal, we evaluated Her2/neu mRNA expression by real-time quantitative RT-PCR, gene amplification by FISH and protein expression by IHC. RESULTS: An excellent correlation between FISH and IHC Her2/neu results was observed, confirming that protein levels were directly related to DNA amplification. Polysomy 17 was frequently found in tumors showing Her2/neu overexpression. However, we did not find any statistically significant correlation among DNA, mRNA and protein levels, suggesting that Her2/neu could be post-transcriptionally regulated. CONCLUSIONS: There was a highagreement between Her2/neu gene amplification and protein overexpression but not mRNA expression levels. Nevertheless, IHC3+ and FISH-positive tumors indicated higher expression levels of Her2/neu mRNA by RT-PCR than those observed in IHC and FISH-negative tumors. These findings question the relevance of quantitative RT-PCR in routine assessment of Her2/neu overexpression in human breast cancer in the clinical laboratory setting.

[Multiple insufficiency fractures (metatarsial, calcaneal and sacral) as the first manifestation of lung adenocarcinoma. A case report and literature review]. / Fracturas múltiples por insuficiencia (metatarsianos, calcáneo y sacro) como signo inicial de adenocarcinoma pulmonar. Caso clínico y revisión de la literatura.

Insufficiency fractures, or pathological fractures, are produced after minimal trauma or no prior trauma and normally affect weakened bone. Their presence should be suspected in fractures showing abnormal patterns, when several fractures occur in a short period of time and in those with no apparent or only minimal trauma. On confirmation of an insufficiency fracture, a differential diagnosis should be made between tumoral and metastatic fractures if there is a history of underlying primary malignancy. The epidemiology of lung cancer has changed due to women's adoption of smoking. In women, the most frequent type of lung cancer is adenocarcinoma, which is less aggressive and has lower mortality, with 5-year survival of 9.5%. Consequently, in Spain, 44% of pulmonary nodules are due to adenocarcinomas. Therefore, all solitary pulmonary nodules should be followed-up for at least 5 years. A history of solitary pulmonary nodule is found in one out of every 1,000 x-rays. However, in patients younger than 35 years, only 1% is malignant. In persons with a history of malignancy and age older than 35 years, this percentage increases to 68%. Size larger than 3cm increases the percentage of malignancy to up to 93%. Therefore, in female smokers older than 50 years with a history of solitary pulmonary nodule, the nodule should be considered malignant until demonstrated otherwise. We report for the first time in Spain the case of a woman with risk factors (smoking, age older than 50 years, with a 3-cm solitary pulmonary nodule that showed no significant growth in 3 years) who had multiple insufficiency fractures in a short period of time. Rehabilitation therapy was unsuccessful and the patient underwent investigation for malignancy. Unfortunately, histopathological study confirmed that the fractures were the initial manifestation of lung adenocarcinoma.

[Tarlov cyst and faecal incontinence: A case report and literature review]. / Quiste de Tarlov e incontinencia fecal: caso clínico y revisión de la literatura.

Tarlov, or perineural cysts, are lesions of the nerve root usually located at the sacral level of the spine. Their cause is unclear. These cysts are generally identified as an incidental finding and are usually asymptomatic. Symptomatic cysts are infrequent, with symptoms usually consisting of pain, radiculopathy and, less frequently, bladder, bowel and sexual dysfunction. We report the case of a 70-year-old woman with Tarlov cyst, provoking faecal incontinence, and review the aetiology, pathophysiology and management of this particular case.

[Effectiveness of multimodal rehabilitation (biofeedback plus capacitive-resistive radiofrequency) on chronic pelvic pain and dyspareunia: prospective study and literature review]. / Efectividad de la rehabilitación multimodal (biofeedback más radiofrecuencia capacitiva-resistiva) sobre el dolor pélvico crónico y la dispareunia: estudio prospectivo y revisión de la bibliografía.

OBJECTIVE: To determine whether a multimodal rehabilitation protocol (Biofeedback [BFB] plus capacitive-resistive [INDIBA®] radiofrequency [RF]) reduces pain and increases muscular strength in patients with chronic pelvic pain (CPP) and dyspareunia. MATERIAL AND METHODS: We performed a prospective, quasi-experimental, before-after study in 37 patients with CPP and/or dyspareunia referred to the Rehabilitation Department of Hospital Universitario Santa Cristina (January 2016 to December 2018). The protocol consisted of 8 sessions of pelvic floor exercises assisted by manometric BFB (15min of tonic/phasic exercises each) supervised by a physiotherapist, followed by suprapubic and perineovaginal bipolar RF [capacitive(5 min)/resistive(10 min)]. The variables evaluated were pain (VAS 0-10) and strength (mmHg) of the pelvic floor musculature and the start/end of the treatment. RESULTS: The mean age was 41.5±12.65 years. The prevalence was higher among women aged 21-40 years (n=20, 54%) and those aged 41-60 years (n=12; 32.4%). Dyspareunia was present in 34 patients (91.8%), and non-specific CPP in 3 (8.2%). The protocol improved pain (from 7.27±1.34 to 3.75±2.21 points), maximal muscular strength (from 25.56±15.9mmHg to 35.35±20.4mmHg) and mean muscular strength (from 4.86±3.53mmHg to 7.18±4.46mmHg) respectively (p<0.0001). CONCLUSION: CPP and dyspareunia are a diagnostic challenge that requires multidisciplinary management. Treatment should be started early and should consist of distinct therapeutic modalities. The protocol of multimodal rehabilitation including BFB and capacitive-resistive RF reduces pain and improves strength in patients with CPP and dyspareunia.

Correction to: BRG1 regulation by miR-155 in human leukemia and lymphoma cell lines.

Following the publication of the original article the author listed as Antonio Herrera contacted the Publisher to state that his correct and full name is Antonio Herrera-Merchan. Antonio Herrera-Merchan has agreed to the publication of this erratum.

[Effectiveness of 6 manometric biofeedback sessions on urinary incontinence and quality of life: A before-after study of 67 patients]. / Efectividad de 6 sesiones de biofeedback manométrico en la incontinencia urinaria y la calidad de vida: estudio prospectivo tipo antes-después, 67 casos.

OBJECTIVE: To determine whether a short 6-session protocol of tonic/ phasic exercises can enhance quality of life and muscular strength in patients with urinary incontinence (UI). MATERIAL AND METHODS: A prospective before-after study was performed in 67 patients with UI referred to the Rehabilitation Department of the Santa Cristina University Hospital in Madrid, Spain. In the initial assessment, the patient's personal details, predisposing factors and type of UI were registered. Patients received lifestyle recommendations. The ICIQ-SF/I-QOL questionnaires/scales were completed at the beginning and end of treatment. The manometric evaluation was registered in the first and last assessment by the MYOMED® 932 equipment. The protocol consisted of a 30-minute session of tonic/phasic exercises (15minutes each) twice weekly for a maximum of 6 sessions, supervised by a physiotherapist. RESULTS: The mean age was 52.1±12.7 years and 94% of the patients (n=63) were women. The maximum and mean strength of the pelvic floor contraction was 26.4±15.6 and 5.3±3.9mmHg, respectively, which significantly increased after treatment to 35.5±19.6 and 7.6±4.4mmHg (P<.0001). The ICIQ-SF score was 10.1±5 and significantly decreased to 6.6±4.6 (P<0.0001). The I-QOL score significantly increased from 66.1±21.9 to 77.9±18.1 points (P<.0001). The I-QOL ALB subscale (avoidance and limiting behaviour) increased from 63.7±22.6 to 77.3±17.8 (P<.0001); the I-QoL PSI subscale (psychosocial impact) increased from 73.8±23.9 to 82.5±18.7 (P=.0004); and the I-QOL SE subscale (social embarrassment) increased from 56.5±23.7 to 70.5±22.1 (P<.0001). CONCLUSION: Manometric feedback reduces UI and improves both quality of life and manometric values. This short 6-session protocol could be applied in other public and private centres and could provide economic benefits to the health system and to patients.

BRG1 regulation by miR-155 in human leukemia and lymphoma cell lines.

INTRODUCTION/PURPOSE: BRG1 is a key regulator of leukemia stem cells. Indeed, it has been observed that this type of cells is unable to divide, survive and develop new tumors when BRG1 is down-regulated. MATERIALS AND METHODS: We assessed BRG1 and miR-155 expression in 23 leukemia cell lines, and two no pathological lymphocyte samples using qPCR. MiR-155 transfection and western blot were used to analyze the relationship between miR-155 and its validated target, BRG1, by measuring protein expression levels. The effect of miR-155 on cell proliferation and prednisolone sensitivity were studied with resazurin assay. RESULTS: BRG1 expression levels could correlate negatively with miR-155 expression levels, at least in Burkitt's lymphoma and diffuse large B cell lymphoma (DLBCL) cell lines. To clarify the role of miR-155 in the regulation of BRG1 expression, we administrated miR-155 mimics in different leukemia/lymphoma cell lines. Our results suggest that miR-155 regulate negatively and significantly the BRG1 expression at least in the MOLT4 cell line. CONCLUSION: Our study revealed a previously unknown miR-155 heterogeneity that could result in differences in the treatment with miRNAs in our attempt to inhibit BRG1. However, the expression levels of BRG1 and miR-155, before prednisolone treatment were not statistically significantly associated prednisolone sensitive leukemia cells.

A haplotype containing the p53 polymorphisms Ins16bp and Arg72Pro modifies cancer risk in BRCA2 mutation carriers.

Germline mutations in the BRCA1 and BRCA2 genes confer a high lifetime risk of developing breast and other cancers; however, remarkable differences exist regarding disease manifestation in mutation carriers. It has been suggested that other genetic and/or environmental factors modify not only the appearance but also the age of onset and type of tumor in BRCA1/2-associated cases. The aim of the present study was to investigate the role of two p53 polymorphisms (c.97-147ins16bp and c.215c>g, p.Arg72Pro) as potential modifiers. For this purpose we investigated the possible association between the two polymorphisms and disease status in 447 BRCA1/2 mutation carriers belonging to 170 Spanish breast and/or ovarian cancer families. Genotype and haplotype analyses revealed that the presence of a specific haplotype carrying the allele without the 16-bp insertion and the variant allele for the Arg72Pro (No Ins-72Pro haplotype) was associated with an earlier age of onset in BRCA2 mutation carriers. We found an increased risk of developing a first primary tumor (breast or ovarian) before 35 years of age for individuals who carried at least one No Ins-72Pro haplotype (OR: 2.69; 95% CI: 1.15-6.29; P=0.022). We confirmed these data by a functional study in which we compared different p53 genotypes in relation to their apoptotic response after cell treatment with a cytotoxic drug (AraC). Our results revealed a decrease in p53 apoptotic rate associated with the No Ins-72Pro haplotype.

Differential expression of NF-kappaB pathway genes among peripheral T-cell lymphomas.

Nuclear factor kappa B (NF-kappaB) is one important pathway in T-cell proliferation and survival. In a previously reported microarray study, we found NF-kappaB pathway genes differentially expressed between peripheral (PTCL) and lymphoblastic lymphomas. Here, we investigated the expression of NF-kappaB pathway genes using cDNA microarrays in a group of 62 PTCL and in reactive lymph nodes. We found two different subgroups of PTCL based on the expression of NF-kappaB pathway genes. One-third of PTCL showed clearly reduced expression of NF-kappaB genes, while the other group was characterized by high expression of these genes. This distinction was found among all T-cell lymphoma categories analyzed (PTCL unspecified, angioimmunoblastic, cutaneous and natural killer/T lymphomas) with the exception of anaplastic lymphomas (ALCL), which were characterized by reduced NF-kappaB expression in anaplastic cells. Quantitative RT-PCR and immunohistochemical analysis of NF-kappaB-p65 protein confirmed these differences among PTCL subgroups. Importantly, we found that differentiation between NF-kappaB-positive and -negative PTCL could be of clinical interest. The expression profile associated to reduced expression of NF-kappaB genes was significantly associated with shorter survival of patients and seems to be an independent prognostic factor in a multivariate analysis.

The origin and differentiation of microglial cells during development.

Some authors claim that microglia originate from the neuroepithelium, although most now believe that microglial cells are of mesodermal origin, and probably belong to the monocyte/macrophage cell line. These cells must enter the developing central nervous system (CNS) from the blood stream, the ventricular space or the meninges. Afterward microglial cells are distributed more or less homogeneously through the entire nervous parenchyma. Stereotyped patterns of migration have been recognized during development, in which long-distance tangential migration precedes radial migration of individual cells. Microglial cells moving through the nervous parenchyma are ameboid microglia, which apparently differentiate into ramified microglia after reaching their definitive location. This is supported by the presence of cells showing intermediate features between those of ameboid and ramified microglia. The factors that control the invasion of the nervous parenchyma, migration within the developing CNS and differentiation of microglial cells are not well known. These phenomena apparently depend on environmental factors such as soluble or cell-surface bound molecules and components of the extracellular matrix. Microglial cells within the developing CNS are involved in clearing cell debris and withdrawing misdirected or transitory axons, and presumably support cell survival and neurite growth.

Ozono y COVID-19: bases fisiológicas y sus posibilidades terapéuticas según el estadio evolutivo de la infección por SARS-CoV-2 / Ozone and COVID-19: physiological bases and their therapeutic possibilities according to the evolutionary stage in SARS-CoV-2 infection

No existe a la fecha un tratamiento definitivo para la nueva pandemia SARS-CoV-2. Están reconocidos tres estadios evolutivos en la infección por SARS-CoV-2 (infección temprana, fase pulmonar e hiperinflamación sistémica), con signos y síntomas clínicos característicos. Hay en marcha 80 ensayos experimentales internacionales que buscan un tratamiento efectivo para la pandemia COVID-19. De ellos, solo hay tres que consideran como alternativa de tratamiento la ozonoterapia (autohemoterapia mayor). No existe ningún estudio que evalúe la insuflación rectal de ozono, a pesar de ser una técnica segura, barata, sin riesgos y que es una vía de administración sistémica (oxígeno-ozono 95 %-5 %) y que justifica la realización de ensayos clínicos para validar las propiedades teóricas del ozono en el manejo del SARS-CoV-2, dados los excelentes resultados observados en el manejo del ébola. El ozono tiene demostradas cuatro propiedades biológicas que podrían ser de potencial utilidad teórica como terapia complementaria en las diferentes fases de la infección por SARS-CoV-2. El ozono podría inactivar el virus por oxidación indirecta (ROS y LOP) y podría estimular el sistema inmune celular y humoral, siendo útil en la fase de infección temprana (estadios 1 y 2a). El ozono puede mejorar el intercambio gaseoso, reducir la inflamación y modular el sistema antioxidante, por lo que sería útil en la fase de hiperinflamación o "tormenta de citocinas", y en la fase de hipoxemia y/o fallo multiorgánico (estadios 2b y estadio 3). Dada la actual pandemia, urge llevar a cabo un estudio experimental que confirme o descarte las propiedades biológicas del ozono y le permita así ser una terapia complementaria o compasiva para el manejo efectivo de la infección por SARS-CoV-2.(AU)

To date, there is no definitive treatment for the new SARS-CoV-2 pandemic. Three evolutionary stages are recognized in SARS-CoV-2 infection (early infection, pulmonary phase and systemic hyperinflammation), with characteristic clinical signs and symptoms. There are 80 international experimental trials underway seeking an effective treatment for the COVID-19 pandemic. Of them, there are only 3 that consider to Ozone Therapy as an alternative (major auto hemotherapy). There is no study that evaluates Rectal Ozone Insufflation, despite being a safe, cheap, risk-free technique and that it is a systemic administration route (Oxygen-Ozone 95 %-5 %) and that justifies conducting clinical trials to validate the theoretical properties of Ozone in the management of SARS-CoV-2, given the excellent results observed in the management of ebola. Ozone has 4 proven biological properties that could be of potential theoretical utility as a complementary therapy in the different phases of SARS-CoV-2 infection. Ozone could inactivate the virus by indirect oxidation (ROS and LOP) and could stimulate the cellular and humoral immune system, being useful in the early infection phase (stages 1 and 2a). Ozone can improve gas exchange, reduce inflammation, and modulate the antioxidant system, so it would be useful in the hyperinflammation or cytokine storm phase, and in the hypoxemia and / or multi-organ failure phase (stages 2b and stage 3). Given the current pandemic, it is urgent to carry out an experimental study to confirm or rule out the biological properties of Ozone and thus allow it to be a complementary or compassionate therapy for the effective management of SARS-CoV-2 infection.(AU)

Un nuevo paradigma para el tratamiento de la osteoartritis de rodilla: el papel del ácido hialurónico, el plasma rico en plaquetas (PRP) y el ozono en la modulación de la inflamación: una revisión / A new paradigm for the treatment of knee osteoarthritis: the role of hyaluronic acid, platelet-rich plasma (prp) and ozone in the modulation of inflammation: a review

Introducción: La osteoartritis (OA) es la causa más común de la artritis. Tradicionalmente, la OA se consideraba como una enfermedad de "desgaste". Sin embargo, los factores metabólicos e inflamatorios se están considerando ahora como los factores patogénicos hasta el punto de que algunos autores están redefiniendo la OA como una enfermedad de "inflamación crónica de bajo grado". Evidencia: En la artrosis de rodilla están involucradas muchas vías de señalización y mediadores inflamatorios. El nuevo paradigma de tratamiento se basa en los tratamientos celulares sobre las vías de señalización de la inflamación, basados en componentes celulares y proteicos para combatir el entorno inflamatorio de la articulación artrósica y regenerar el tejido dañado. Resultados: El enfoque de tratar solo una diana terapéutica (inhibidores de óxido nítrico, nutracéuticos, agentes reductores de uratos y fármacos biológicos) que han demostrado su eficacia en el tratamiento de enfermedades inflamatorias como la artritis reumatoide no se ha traducido en un manejo eficaz de la OA. Un enfoque de tratamiento dirigido simultáneamente a varias dianas sería capaz de manejar la OA de manera más eficiente. Las pautas estándar (AAOS, OARSI, ACR, NICE o EULAR) no consideran el ácido hialurónico, el plasma rico en plaquetas ni el ozono, aunque estas opciones de tratamiento han mostrado propiedades inmunomoduladoras y curativas. En ese escenario, planteamos la hipótesis de que el ácido hialurónico, el plasma rico en plaquetas y el ozono son alternativas prometedoras para el manejo de la OA de rodilla, debido a sus propiedades multidiana, como se observará en esta revisión. Conclusión: En el presente estudio se ha revisado la fisiopatología de la OA, centrándose principalmente en el mecanismo inflamatorio, las vías de señalización implicadas y los posibles objetivos del tratamiento...(AU)

Introduction: Osteoarthritis (OA) is the most common cause of arthritis. Traditionally, OA was viewed as a "wear and tear" disease. However, metabolic and inflammatory factors are now being considered as pathogenic factors to the point that some authors are redefining OA as a "chronic low-grade inflammation" disease. Evidence: In knee osteoarthritis, many inflammatory signaling pathways and mediators are involved. The new treatment paradigm is based on cellular treatments on the signaling pathways of inflammation, based on cellular and protein components to combat the inflammatory environment of the arthritic joint and regenerate damaged tissue. Results: The approach of treating only one therapeutic target (nitric oxide inhibitors, nutraceuticals, urate reducing agents, and biologics) that have demonstrated their efficacy in the treatment of inflammatory diseases such as rheumatoid arthritis has not been translated into effective management in OA. A treatment approach aimed simultaneously at multiple targets would be able to manage OA more efficiently. The standard guidelines (AAOS, OARSI, ACR, NICE, or EULAR) do not consider hyaluronic acid, platelet-rich plasma, or ozone, although these treatment options have shown immunomodulatory and healing properties. In this scenario, we hypothesized that hyaluronic acid, platelet-rich plasma, and ozone are promising alternatives for the management of knee OA, due to their multidial properties, as will be seen in this review. Conclusion: In the present study the pathophysiology of OA has been reviewed, focusing mainly on the inflammatory mechanism, the signaling pathways involved and the possible goals of treatment. Hyaluronic acid, platelet-rich plasma and ozone are proposed as multi-target options for the treatment of knee osteoarthritis.

Effect of Lippia alba and Cymbopogon citratus essential oils on biofilms of Streptococcus mutans and cytotoxicity in CHO cells.

BACKGROUND: Caries is a public health problem, given that it prevails in 60 to 90% of the school-age global population. Multiple factors interact in its etiology, among them dental plaque is necessary to have lactic acid producing microorganisms like Streptococcus from he Mutans group. Existing prevention and treatment measures are not totally effective and generate adverse effects, which is why it is necessary to search for complementary strategies for their management. AIM: The study sought to evaluate the eradication capacity of Streptococcus mutans biofilms and the toxicity on eukaryotic cells of Lippia alba and Cymbopogon citratus essential oils. METHODOLOGY: Essential oils were extracted from plant material through steam distillation and then its chemical composition was determined. The MBEC-high-throughput (MBEC-HTP) (Innovotech, Edmonton, Alberta, Canada) assay used to determine the eradication concentration of S. mutans ATCC 35668 strain biofilms. Cytotoxicity was evaluated on CHO cells through the MTT cell proliferation assay. RESULTS: The major components in both oils were Geraniol and Citral; in L. alba 18.9% and 15.9%, respectively, and in C. citratus 31.3% and 26.7%. The L. alba essential oils presented eradication activity against S. mutans biofilms of 95.8% in 0.01mg/dL concentration and C. citratus essential oils showed said eradication activity of 95.4% at 0.1, 0.01mg/dL concentrations and of 93.1% in the 0.001mg/dL concentration; none of the concentrations of both essential oils showed toxicity on CHO cells during 24h. CONCLUSION: The L. alba and C. citratus essential oils showed eradication activity against S. mutans biofilms and null cytotoxicity, evidencing the need to conduct further studies that can identify their active components and in order to guide a safe use in treating and preventing dental caries.

First appearance, distribution, and origin of macrophages in the early development of the avian central nervous system.

A phagocytic cell system of hemopoietic origin exists in the early avian embryo (Cuadros, Coltey, Nieto, and Martin: Development 115:157-168, '92). In this study we investigated the presence of cells belonging to this system in the central nervous system (CNS) of chick and quail embryos by using both histochemical staining for acid phosphatase and immunolabelling with antibodies recognizing cells of quail hemangioblastic lineage. The origin of these cells was traced in interspecific chick-quail yolk sac chimeras. Hemopoietic cells were detected within the CNS from developmental stage HH15 on, and steadily increased in number at subsequent stages. Analysis of yolk sac chimeras revealed that most of these cells were of yolk sac origin, although some hemopoietic cells of intramebryonic origin were also found in the CNS. Immunocytochemical, histochemical, and ultrastructural characterization allowed us to identify hemopoietic cells in the CNS as macrophages. These cells were consistently found in the brain vesicles and spinal cord, appearing (1) between undifferentiated neuroepithelial cells at dorsal levels of the CNS; (2) in areas of cell death; (3) in the marginal layer in close relationship with developing axons; (4) in large extracellular spaces in the subventricular layer; (5) on vascular buds growing through the marginal and subventricular layers; and (6) in the ventricular lumen. Macrophages in different locations varied in morphology and ultrastructure, suggesting that in addition to their involvement in phagocytosis, they play a role in other processes in the developing CNS, such as axonal growth and vascular development. The first macrophages migrate to the CNS independently of its vascularization, apparently traversing the pial basal lamina to reach the nervous parenchyma. Other macrophages may enter the CNS together with vascular buds at subsequent stages during CNS vascularization.