Frequency of Gene Polymorphisms in Admixed Venezuelan Women with Recurrent Pregnancy Loss: Microsomal Epoxy Hydroxylase (rs1051740) and Enos (rs1799983).

Recurrent pregnancy loss (RPL) affects around 2% of women of reproductive age. Primary RPL is defined by ≥2 pregnancy losses and no normal birth delivery. In secondary RPL, the losses are after a normal pregnancy and delivery. Most cases have no clear aetiology, although primary cases are the most complex. Several gene single nucleotide polymorphisms (SNPs) have been associated with RPL. The frequency of some SNPs is increased in women suffering from RLP from Asian or Caucasian races; however, in admixed populations, the information on possible genetic links is scarce and contradictory. This study aimed to assess the frequency of two SNPs present in two different enzymes involved in medical conditions observed during pregnancy. It is a case-control study. Microsomal epoxy hydrolase (mEPH) is involved in detoxifying xenobiotics, is present in the ovaries, and is hormonally regulated. The endothelial nitric oxide synthase (NOS3) that forms nitric is involved in vascular tone. Two SNPs, rs1051740 (mEPH) and rs1799983 (NOS3), were assessed. The study included 50 controls and 63 primary RPL patients. The frequency of mutated alleles in both SNPs was significantly higher in patients (p < 0.05). Double-mutated homozygotes were encountered only in RPL patients (p < 0.05). Genetic polymorphisms rs1051740 and rs1799983 may be involved in primary RPL in the Venezuelan admix population. Genetic studies could provide crucial information on the aetiology of primary RPL.

Inflammation, Autoimmunity and Neurodegenerative Diseases, Therapeutics and Beyond.

Neurodegenerative disease (ND) incidence has recently increased due to improved life expectancy. Alzheimer's (AD) or Parkinson's disease (PD) are the most prevalent NDs. Both diseases are poly genetic, multifactorial and heterogenous. Preventive medicine, a healthy diet, exercise, and controlling comorbidities may delay the onset. After the diseases are diagnosed, therapy is needed to slow progression. Recent studies show that local, peripheral and age-related inflammation accelerates NDs' onset and progression. Patients with autoimmune disorders like inflammatory bowel disease (IBD) could be at higher risk of developing AD or PD. However, no increase in ND incidence has been reported if the patients are adequately diagnosed and treated. Autoantibodies against abnormal tau, ß amyloid and α- synuclein have been encountered in AD and PD and may be protective. This discovery led to the proposal of immune-based therapies for AD and PD involving monoclonal antibodies, immunization/ vaccines, pro-inflammatory cytokine inhibition and anti-inflammatory cytokine addition. All the different approaches have been analysed here. Future perspectives on new therapeutic strategies for both disorders are concisely examined.

Autoimmunity and Immunodeficiency in Severe SARS-CoV-2 Infection and Prolonged COVID-19.

SARS-CoV-2 causes the complex and heterogeneous illness known as COVID-19. The disease primarily affects the respiratory system but can quickly become systemic, harming multiple organs and leading to long-lasting sequelae in some patients. Most infected individuals are asymptomatic or present mild symptoms. Antibodies, complement, and immune cells can efficiently eliminate the virus. However, 20% of individuals develop severe respiratory illness and multiple organ failure. Virus replication has been described in several organs in patients who died from COVID-19, suggesting a compromised immune response. Immunodeficiency and autoimmunity are responsible for this impairment and facilitate viral escape. Mutations in IFN signal transduction and T cell activation are responsible for the inadequate response in young individuals. Autoantibodies are accountable for secondary immunodeficiency in patients with severe infection or prolonged COVID-19. Antibodies against cytokines (interferons α, γ and ω, IL1ß, IL6, IL10, IL-17, IL21), chemokines, complement, nuclear proteins and DNA, anticardiolipin, and several extracellular proteins have been reported. The type and titer of autoantibodies depend on age and gender. Organ-specific autoantibodies have been described in prolonged COVID-19. Their role in the disease is under study. Autoimmunity and immunodeficiency should be screened as risk factors for severe or prolonged COVID-19.

Polimorfismos de nucleótidos simples V4 y T1 del gen ADAM33 en pacientes venezolanos con asma o enfermedad pulmonar obstructiva crónica / Single nucleotide polymorphisms V4 and T1 of the ADAM33 gene in Venezuelan patients with asthma or chronic obstructive pulmonary disease

ADAM33 es una metaloproteinasa de la matriz extracelular involucrada en la remodelación tisular y, por ello, en el asma y la enfermedad pulmonar obstructiva crónica (EPOC). Se han reportado varios polimorfismos del gen de ADAM33 asociados a la actividad enzimática. Los polimorfismos más estudiados son el V4, citosina por una guanina en la región 3’ UTR, y el T1, adenina por una guanina en el exón 19 del gen. El objetivo del presente trabajo fue determinar la posible asociación de los polimorfismos de nucleótido simple de ADAM33, V4 y T1, con la presencia de asma o EPOC en pacientes venezolanos. Los polimorfismos V4 y T1 fueron analizados en 303 individuos (103 asmáticos, 100 EPOC, y 100 controles) mediante PCR-RFLP (reacción en cadena de la polimerasa y análisis de polimorfismos por longitud de fragmentos de restricción enzimática). La frecuencia genotípica del polimorfismo V4 fue significativamente mayor (p<0,05) en ambos grupos de pacientes, asmáticos y EPOC, con respecto al control. No se encontraron diferencias significativas (P=0,4) en el polimorfismo T1. Sin embargo, se evidenció una diferencia significativa (p<0,05) cuando los haplotipos y diplotipos de ADAM33 V4/T1 se compararon entre los tres grupos. Se concluye que el polimorfismo ADAM33 V4 está asociado con la presencia de asma o EPOC en pacientes venezolanos.

ADAM33 is a metalloproteinase important in the extracellular matrix for tissue remodeling, and, consequently, in asthma and chronic obstructive pulmonary disease (COPD). Several polymorphisms of the ADAM33 gene have been associated with enzyme activity. One of the most studied polymorphisms is V4, cytosine for guanine in the 3’UTR region, and T1, adenine for guanine in the exon 19 of the gen. The aim of this study was to ascertain the possible association among single polymorphisms of ADAM33, V4 and T1, in Venezuelan patients with asthma or COPD. The polymorphisms V4 and T1 were analyzed in 303 individuals (103 asthmatic, 100 COPD and 100 controls) by PCR-RFLP (polymerase chain reaction and restriction fragment length polymorphisms). There was a significant difference (P<0.05) in the frequency of ADAM33 V4 polymorphism in both, asthmatic and COPD patients groups, as compared to controls. No significant differences (P=0.4) were found for T1 polymorphism. However, there were significant differences (P<0.05) when haplotypes and diplotypes of ADAM33 V4/T1 were compared in all three groups. It can be concluded that the polymorphism V4 of ADAM33 is associated with asthma or COPD in Venezuelan patients.

Single nucleotide polymorphisms V4 and T1 of the ADAM33 gene in Venezuelan patients with asthma or chronic obstructive pulmonary disease.

ADAM33 is a metalloproteinase important in the extracellular matrix for tissue remodeling, and, consequently, in asthma and chronic obstructive pulmonary disease (COPD). Several polymorphisms of the ADAM33 gene have been associated with enzyme activity. One of the most studied polymorphisms is V4, cytosine for guanine in the 3 'UTR region, and T1, adenine for guanine in the exon 19 of the gen. The aim of this study was to ascertain the possible association among single polymorphisms of ADAM33, V4 and T1, in Venezuelan patients with asthma or COPD. The polymorphisms V4 and T1 were analyzed in 303 individuals (103 asth- matic, 100 COPD and 100 controls) by PCR-RFLP (polymerase chain reaction and restriction fragment length polymorphisms). There was a significant difference (P<0.05) in the frequency of ADAM33 V4 polymorphism in both, asthmatic and COPD patients groups, as compared to controls. No significant differences (P=0.4) were found for T1 polymorphism. However, there were significant differences (P

Vaccine therapy update for pregnant, immunocompromised, and chronic diseases patients.

The use of vaccines in pregnant, immunocompromised or chronic diseases patients has been widely discussed in the literature recently. Vaccines continue to be a safe and effective method to induce or recall immune response to several infective agents or even induce an effective response in chronically infected patients. The general presumption of adverse events, lack of response and unwanted tolerance seem to be responsible for the decreased vaccination rate in these patients. In the present review, the use of rational vaccination schemes, new patents of use, along as new approaches and patents have been discussed with the scope to diminish the high morbidity and mortality often encountered in these patients.

Study of the fibrinolytic process in a patient with antiphospholipid syndrome.

The antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of antibodies against ß2-Glycoprotein I (aß2-GPI), cardiolipin (aCL) and lupus anticoagulant combined with venous or arterial thrombosis and/or foetal losses. A 28-year-old female was positive for aß2-GPI, aCL, aPT (antibodies against prothrombin) and lupus anticoagulant. She had two miscarriages and a deep vein thrombosis event. The patient plasma fibrinogen and IgG concentrations were two times higher than control. Fibrinolysis was induced in vitro adding tPA, before clotting plasma with 0.03 or 0.6 IU/ml thrombin, and in purified system with normal fibrinogen in the presence of 0.5 mg/ml of patient or normal IgG. The APS patient had 1.5 and 1.9 times higher clot rate formation (CRL) and maximum absorbance (MaxAbsL) at both thrombin concentrations. At 0.6 IU/ml of thrombin, the patient delay on fibrin polymerization onset was corrected. The patient Lys50MA (time needed for 50% clot dissolution) was slower (P < 0.05) at 0.03 IU/ml of thrombin; however, the lysis rate was faster at both thrombin concentrations. After adjusting the polymerization and fibrinolytic parameters according to the sample plasma fibrinogen concentration, there were almost no differences between patient and control at 0.6 IU/ml. In an IgG-fibrinogen purified system, fibrinolysis was equivalent in the presence of patient or normal IgG. In conclusion, the patient IgG fraction has no inhibitors against proteins of the fibrinolytic pathway. The differences observed between the APS patient and the control were more evident at low thrombin concentration due to the presence of aPT.

Metabolic syndrome and asthma.

Metabolic syndrome (MetS) is a syndrome that involves at least three disorders dyslipidemia, insulin resistance, obesity and/or hypertension. MetS has been associated with several chronic diseases in the adulthood; however, in the recent years, the syndrome was redefined in children. Girls with early menarche and asthma, and children with MetS and asthma that reach adulthood appear to have higher risk to develop severe or difficult to control asthma and a higher probability to suffer cardiovascular diseases. It has been proposed that patients with MetS and endocrinological disorders should be considered a different entity in which pharmacologic treatment should be adjusted according to the individual. Recent patents on the field have addressed new issues on how endocrine control should be managed along with asthma therapeutics. In the near future, new approaches should decrease the high morbidity and mortality associated to these types of patients.

Beta 2 adrenergic receptor polymorphisms, at codons 16 and 27, and bronchodilator responses in adult Venezuelan asthmatic patients.

BACKGROUND: One of the gene polymorphisms often studied in asthmatic patients is the ß2 adrenergic receptor (ADRß2). Even though in the Venezuelan Mestizo population there is a high incidence of asthma, there are no direct reports of ADRß2 gene polymorphism, and treatment response. The aim of this study was to assess, in this population, the gene frequency of ADRß2 polymorphisms at codons 16 Arg/Gly and 27 Gln/Glu, allergen sensitization, and its relationship to bronchodilator response. METHODS: Purified genomic DNA was obtained form 105 Mestizo asthmatic and 100 Mestizo healthy individuals from Venezuela. The two polymorphisms were assessed by PCR-RFLP. Patient sensitization to aeroallergens and their response to bronchodilatation were correlated. RESULTS: Significant differences between patients and controls were recorded in: 1) the prevalence of Arg/Arg at codon 16 (28.6% in patients vs. 47% in controls, P<0.01), 2) the frequency of heterozygotes Arg/Gly (55% in patients vs. 35% in controls, P<0.01). Conversely, no differences in polymorphism frequencies were found at codon 27. The haplotypes Arg/Gly-Gln/Gln were more common in patients than controls (P <0.01), whereas the Arg/Arg-Gln/Glu combination prevailed in the control group (P<0.01). The Arg/Gly and Gln/Glu genotypes were associated with better responses after salbutamol. The asthmatic homozygotes Arg/Arg have higher sensitivity to aeroallergens. CONCLUSION: The difference in Arg/Arg frequency between groups suggests that this could be a protective genotype although the asthmatic group had a higher sensitivity to aeroallergens. The asthmatic heterozygotes had better bronchodilator responses than the homozygotes.

Sensibilización al maní en pacientes venezolanos con enfermedades atópicas y/o urticaria / Sensitization to peanut in Venezuelan patients with atopic diseases and / or uticaria

La sensibilización y las manifestaciones alérgicas al maní se han incrementado últimamente a nivel mundial, constituyendo el mismo la causa principal de anafilaxia por alimentos. Como la prevalencia de alergia al maní varía de acuerdo a las regiones nos propusimos evaluar, en una etapa preliminar, la sensibilización al maní por pruebas cutáneas (“skin prick test”) en pacientes venezolanos atópicos y/o con urticarias que acudieron a la Consulta ambulatoria de Alergía del Instituto de Inmunología. El 5,4 % de los pacientes manifestó algún tipo de manifestación cutánea o respiratoria al ingerir maní. Se demostró sensibilización al maní por pruebas cutánea en el 6,5 % de los pacientes. Sin embargo, un porcentaje pequeño (2 %) de ellos mostró, en conjunto, pruebas cutáneas positivas y síntomas a la ingesta del maní. Ningún paciente refirió síntomas severos tras la ingestión de maní. La mayoría de los pacientes con pruebas positivas al maní, también mostraron pruebas positivas a otros alimentos. Estos resultados concuerdan con la percepción de los médicos venezolanos de una baja frecuencia de reacciones adversas, especialmente graves, a la ingesta de maní en nuestro país

Peanut allergy and sensitization incidence has increased world wide to become the first cause of food anaphylaxis. Since the prevalence of peanut allergy changes according to geographical areas, the aim of the study was to assess, in a preliminary report, peanut allergy incidence by skin prick test in atopic Venezuelan patients with atopy and or urticaria from the outpatient allergy clinic of the Institute of Immunology. Cutaneous or respiratory manifestations after peanut ingestion was observed in 5.4 % of the patients studied. Cutaneous test was positive in 6.5 % of patients. In the other hand, a small group (2 %), showed positive skin test along with symptoms after peanut ingestion. None of the patients had severe reactions. Most of the patients with peanut positive skin test were positive to other food allergens. These results are in accordance with the general clinical perception of small frequency of adverse reaction, specially the most serious ones, to peanut ingestion in our country

Perspectives of new therapies for endometriosis.

Endometriosis is an inflammatory disease characterized by the presence of endometrial glandular epithelial and stromal cells growing in the extra-uterine environment. The disease affects: ovarian function, oocyte quality, embryo development and implantation, and uterine function resulting in infertility or spontaneous pregnancy loss. Even though the world's prevalence is above 10 %, an effective treatment has not yet been found. New pharmacological approaches have been designed and patented that could serve as future therapies for this disease.

Role of beta2 agonists in respiratory medicine with particular attention to novel patents and effects on endocrine system and immune response.

Beta adrenergic receptors are very important in respiratory medicine. Traditionally, the stimulation of beta adrenergic receptors by beta2-agonists is commonly used for giving bronchodilation in chronic airflow obstruction However; the wide distribution of these receptors in cells and tissues other than airway smooth muscle suggests that beta agonists should offer other beneficial effects in respiratory disease. Recent studies have shown the importance of these receptors in the modulation of endocrine and immune system that affect respiratory function and may decrease therapy effectiveness in asthma and chronic obstructive pulmonary disease. New patented compound and uses have provided new insights in future therapeutics of respiratory diseases in which genetic, endocrine and immune response should be considered.

Inhibitors of phosphoinositol 3 kinase and NFκB for the treatment of chronic obstructive pulmonary disease.

Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable disease characterized mainly by pulmonary airflow limitation that is not fully reversible. New different pharmacological approaches to decrease inflammation of the airways and consequently disease progression and increase airway obstruction reversibility have been developed. In the present article, we review the new patents on phosphoinositide 3 kinase and NFκb inhibitors for future therapies.

[Effect of antiphospholipid antibodies on the formation and lysis of fibrin network in patients with recurrent miscarriage]. / Efecto de los anticuerpos antifosfolipidicos en la formación y degradación de la malla de fibrina en pacientes con aborto recurrente.

The present work was intended to study the process of fibrin formation and lysis and plasmin generation in a group of patients with recurrent miscarriage (RM), due to the presence of antiphospholipid antibodies (N = 10); as well as in women with RM without the antiphospholipid syndrome (APS) (N = 6), compared with those of a group of healthy women (N= 8). In the group of patients with APS, nine were positive for antibodies against cardiolipin (aCL), five for anti-beta2-glycoprotein I (anti-beta2GPI), four for both antibodies, and one for antibodies against prothrombin (aPT) and lupus anticoagulant (LA). Fibrin formation and lysis was followed by turbidity and plasmin generation using chromogenic substrate S2251. The polymerization curves from RM patients without APS and the LA patient showed an increased slope and maximum turbidity compared to those of the control group. The speed of lysis was higher in the LA patient (21 +/- 0) 10(-4) deltaOD/seg and the RM patients without APS (19.6 +/- 5.7) 10(-4) deltaDO/seg, compared to that of the control group (14.5 +/- 2.8) 10(-4) deltaDO/seg. Plasmin generation increased only in RM patients without APS (85 +/- 24%) against the control group (52 +/- 3%), p = 0.005. The changes observed in the fibrin polymerization and lysis process of women with RM without APS and LA seem to be related to their higher fibrinogen levels, while the increased plasmin generation was related to the patients' morbidity.

New pharmacological treatments for patients with chronic obstructive pulmonary disease (COPD).

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable disease characterized mainly by pulmonary airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with abnormal inflammatory response of the lung to noxious particles or gasses. New different pharmacological approaches to decrease inflammation of the airways and consequently disease progression and increase airway obstruction reversibility have been developed. METHODS AND RESULTS: A literature search using PubMed, Science Direct, EBSCO and free patents on line for the years 2000-2010. CONCLUSIONS: Recent discoveries in the physiology and pathology of airways diseases have served to generate potential new drugs for the treatment of COPD patients. Several substances that block or activate specific pathways and receptors the aim of which is to decrease inflammation and increase airway obstruction reversibility are being used in different clinical protocols and hopefully will be available for patients in the near future.

Efecto de los anticuerpos antifosfolipídicos en la formación y degradación de la malla de fibrina en pacientes con aborto recurrente / Effect of antiphospholipid antibodies on the formation and lysis of fibrin network in patients with recurrent miscarriage

En el presente trabajo se estudió el proceso de formación y disolución de la malla de fibrina y la generación de plasmina en un grupo de pacientes con aborto recurrente (AR) debido a la presencia de anticuerpos antifosfolipídicos (N= 10), mujeres con AR sin el síndrome antifosfolipídico (SAF) (N= 6) y se comparó con un grupo de mujeres sanas (N= 8). Del grupo de pacientes estudiadas con SAF, nueve fueron positivas para anticuerpos anticardiolipina (aCL), cinco para la anti-b2-glicoproteína I (anti-b2GPI), cuatro para ambos anticuerpos, una para anticuerpos antiprotrombina (aPT) y anticoagulante lúpico (AL). El proceso de formación de la fibrina y su disolución fue estudiado por turbidimetría y la generación de plasmina mediante sustrato cromogénico S2251. Las curvas de polimerización de la(s) paciente(s) con AR sin SAF y AL presentaron un incremento en la pendiente y turbidez final, comparado con las del grupo control de mujeres sanas. La velocidad de disolución del coágulo fue mayor en la paciente con AL (21 ± 0) 10-4 DDO/seg y en las AR sin SAF (19,6 ± 5,7) 10-4 DDO/seg, comparado con el grupo control (14,5 ± 2,8) 10-4 DDO/seg. La generación de plasmina estuvo incrementada solamente en las AR sin SAF (85 ± 24%) comparado con 52 ± 3% en el grupo control, p= 0,005. Los cambios observados en el proceso de polimerización y fibrinólisis de la(s) paciente(s) con AR sin SAF y AL pudieran estar relacionados con el incremento en los niveles de fibrinógeno, mientras que los de la generación de plasmina con la entidad mórbida.

The present work was intended to study the process of fibrin formation and lysis and plasmin generation in a group of patients with recurrent miscarriage (RM), due to the presence of antiphospholipid antibodies (N= 10); as well as in women with RM without the antiphospholipid syndrome (APS) (N= 6), compared with those of a group of healthy women (N= 8). In the group of patients with APS, nine were positive for antibodies against cardiolipin (aCL), five for anti-b2-glycoprotein I (anti-b2GPI), four for both antibodies, and one for antibodies against prothrombin (aPT) and lupus anticoagulant (LA). Fibrin formation and lysis was followed by turbidity and plasmin generation using chromogenic substrate S2251. The polymerization curves from RM patients without APS and the LA patient showed an increased slope and maximum turbidity compared to those of the control group. The speed of lysis was higher in the LA patient (21 ± 0) 10-4 DOD/seg and the RM patients without APS (19.6 ± 5.7) 10-4 DDO/seg, compared to that of the control group (14.5 ± 2.8) 10-4 DDO/seg. Plasmin generation increased only in RM patients without APS (85 ± 24%) against the control group (52 ± 3%), p= 0.005. The changes observed in the fibrin polymerization and lysis process of women with RM without APS and LA seem to be related to their higher fibrinogen levels, while the increased plasmin generation was related to the patients´ morbidity.

Prevalencia de la alergia y de la sensibilización al látez en el estudiante de postgrado de la facultad de odontología de la ucv / Prevalence of allergy and sensitization latez graduate student in the faculty of dentistry ucv

a exposición ocupacional al látex incrementa el riesgo de sensibilización al mismo en los profesionales de la salud. El objetivo de este estudio ha sido establecer la prevalencia de la alergia y de la sensibilización al látex en una población conformada por los estudiantes de postgrado de la Facultad de Odontología de la UCV e identificar los posibles factores de riesgo. Pacientes y métodos: Se realizó un cuestionario sobre actividad laboral y antecedentes de síntomas y reacciones alérgicas. También se diagnosticó la hipersensibilidad tipo I mediante la prueba cutánea por técnica de "prick test" como prueba in vivo y un método ELISA utilizando el ENEASystem III como prueba in vitro. Resultados: Estas dos pruebas diagnósticas arrojaron un total de un 32% (27) participantes con hipersensibilidad tipo I al látex. Referente a los factores considerados como de riesgo, 33% (9) de estos pacientes sensibilizados tenían antecedentes familiares de alergia; 44% (12) reportaron antecedentes personales de alergia y 59% (16) habían sido sometidos a intervenciones quirúrgicas. Del total de los individuos sensibilizados al látex 56% (15) manifestaron síntomas respiratorios o cutáneos al entrar en el área odontológica.Conclusiones: En este estudio se encontró una elevada prevalencia de hipersensibilidad tipo I al látex (32%) en los estudiantes de postgrado de la Facultad de Odontología de la UCV, siendo necesario, a futuro, aclarar si esta tendencia se mantiene en un grupo mas heterogéneo (odontólogos y su personal auxiliar)

Occupational exposure increases the risk of latex sensitization in health professionals. The aim of this study was to establish the prevalence of allergy and latex sensitization in graduate students of the Faculty of Dentistry of the Universidad Central de Venezuela and to identify possible risk factors. Patients and methods: We conducted a questionnaire on work activity, history of symptoms and allergic reactions. We diagnosed type I hypersensitivity by skin test as evidence in vivo and an ELISA using ENEASystem III as evidence in vitro. Results: 32% (27) participants were diagnosed with type I hypersensitivity to latex, 33% (9) of sensited participants had family history of allergy, 44% (12) reported a history of allergy and 59% (16) had undergone surgery. Of all patients sensitized to latex 56% (15) reported respiratory symptoms or skin to enter the dental area.Conclusions: This study found a high prevalence of type I hypersensitivity to latex (32%) in students of the Faculty of Dentistry, in future, need to clarify whether this trend continues in a more heterogeneous group (dentists and their staff)

Niveles séricos de metaloproteinasa 9 (mmp-9) y del inhibidor tisular de mmp tipo 1 (timp-1) en pacientes venezolanos con asma o con enfermedad pulmonar obstructiva crónica (epoc) / Serum metalloproteinase 9 (MMP-9) and tissue inhibitor of MMP-1 (TIMP-1) in venezuelan patients with asthma or chronic obstructive pulmonary disease (copd)

Los niveles séricos de la metaloproteinasa (MMP) 9, enzima involucrada en inflamación, y su contraparte, el inhibidor tisular de la metaloproteinasas tipo 1 (TIMP-1), se encuentran significativamente (P < 0,01) incrementados en pacientes con asma o con enfermedad pulmonar obstructiva crónica (EPOC) en comparación con los grupos control del mismo rango etario. El incremento de ambos parámetros se hace más significativo en los pacientes severos de ambos grupos (P < 0,0001) y particularmente en los pacientes con EPOC severo en comparación con los asmáticos severos (P < 0,01). El incremento en los niveles séricos de MMP-9 en relación con severidad es mayor que lo observado para TIMP-1 en ambas patologías. Se concluye que los niveles séricos de MMP-9 y TIMP-1 pueden ser un marcador importante para determinar severidad en estas enfermedades

Serum levels of metalloproteinase (MMP) 9, an enzyme involved in inflammation, and its counterpart, the tissue inhibitor of metalloproteinases type 1 (TIMP-1) are significantly (P < 0.01) increased in patients with asthma or with chronic obstructive pulmonary disease (COPD) as compared with controls of the same age. The increase in both parameters is more significant (P < 0.0001) in severe patients of both groups, and particularly in patients with severe COPD as compared to severe asthmatics (P < 0.01). The increase in serum MMP-9 levels in relation with severity is higher than the observed values for TIMP-1 in both diseases. It is concluded that serum levels of MMP-9 and TIMP-1 may be important markers to establish severity in these diseases

Pharmacological properties of thalidomide and its analogues.

Thalidomide and its immunomodulatory imide drugs (IMiDs) analogues CC-5013 (Revlimid, Lenalidomide) and CC-4047 (Actimid, Pomalidomide) have been used as anti-inflammatory and anticancerous drugs in the recent years. Thalidomide and IMiDs inhibit the cytokines tumour necrosis factor-alpha (TNF-alpha), interleukins (IL) 1-beta, 6, 12, and granulocyte macrophage-colony stimulating factor (GM-CSF). They also costimulate primary human T, NKT and NK lymphocytes inducing their proliferation, cytokine production, and cytotoxic activity. On the other hand, the compounds are anti-angiogenic, anti-proliferative, and pro-apoptotic. Thalidomide analogues have been used as inhibitors of alpha glucosidase and could be potential drugs for diabetes treatment. In this review, we explore the current trend of the different structures, the new patents, and the possible new applications in different pathologies.