Semen Cannabis and Oleum Hyperici: Antileishmanial activity against Leishmania tropica promastigotes and intracellular amastigotes.

The exploration of alternative agents and novel drug candidates for the effective treatment of cutaneous leishmaniasis has garnered significant attention, driven by the high cost, toxic effects, and the emergence of drug resistance associated with current therapeutic options. Plant extracts derived from Semen Cannabis, the seeds of the Cannabis sativa L. (hemp) plant, and Oleum Hyperici, the oily macerate of Hypericum perforatum L. (St. John's Wort) plant, were prepared by using solvents of varying polarity (n-hexane, chloroform, ethanol, and 60% aqueous ethanol). The primary objective of this study was to research in vitro and ex vivo antileishmanial efficacy of Semen Cannabis and Oleum Hyperici plant extracts against Leishmania tropica promastigotes and intracellular amastigotes. The efficacy of plant extracts against promastigotes were assessed using the cell counting by hemocytometer and the CellTiter-Glo assay. Additionally, their impact on infected THP-1 macrophages and the quantity of intracelluler amastigotes were investigated. Cytotoxicity was evaluated in THP-1 macrophages. Among the tested plant extracts, chloroform extract of Oleum Hyperici demonstrated significant antileishmanial activity against promastigotes (SI: 12.6) and intracellular amastigotes (SI: 16.8) of L. tropica without inducing cytotoxic effects and hold promise for further investigation as potential antileishmanial agents.

Does vanillic acid affect fracture healing? An experimental study in a rat model of femur fracture.

BACKGROUND AND OBJECTIVES: We aimed to determine the effects of vanillic acid (VA) on fracture healing radiologically, histologically, immunohistochemically, and biomechanically using a rat femur open fracture injury model. METHODS: 32 male Wistar-Albino rats were used and divided into two groups: the study group (VA) and the control group. From the time they were operated on until they were sacrificed, the rats in the study group were given 100 mg/kg/day VA by oral gavage. After sacrification, the femurs were analyzed. RESULTS: It was observed that the Huo histological scoring was significantly higher in the VA group (p = 0.001), and the ratio of the amount of callus tissue compared to intact bone tissue was significantly higher. While no significant difference was observed in immunohistochemical H-scores in ColI antibody staining (p = 1.000), a borderline significant difference in favor of VA was observed in ColIII antibody staining (p = 0.078). In biomechanical analysis, failure load (N), total energy (J), maximum stress (MPa), and stiffness (N/mm) measurements were significantly higher in the VA group (p = 0.040, p = 0.021, p = 0.015, and p = 0.035, respectively). CONCLUSION: It has been observed that VA, with its antioxidative properties, increases fracture healing in rats, in which an open fracture model was created. We are hopeful that such an antioxidant, which is common in nature, will increase fracture healing. Since this study is the first to examine the effect of VA on fracture healing, further studies are needed.

Psychological risk factors for upper extremity fractures in preschool children: A case-control study.

BACKGROUND: In school-age children, upper extremity fractures are associated with both parental and child-related factors and represent a multifactorial entity. This study aims to explore the psychological risk factors associated with upper extremity fractures in preschool children. METHODS: This single-center, hospital-based, age-matched case-control study involved 55 cases of upper extremity fractures and 55 controls experiencing growing pains. Parents of the children participated in face-to-face interviews. We examined the potential as-sociations between scores on the Mother-to-Infant Bonding Scale (MIBS), Adult Attention Deficit Hyperactivity Disorder Self-Report Scale (ASRS), Autism-Spectrum Quotient (AQ), State-Trait Anxiety Inventory (STAI), and Strengths and Difficulties Questionnaire (SDQ), and the risk of upper extremity fractures. RESULTS: Advanced parental age and lower household income emerged as risk factors for upper extremity fractures, while longer maternal educational attainment was identified as a protective factor. In the univariate analyses, elevated scores on the Autism-Spec-trum Quotient Communication subscale (AQ-C), overall AQ score, Strengths and Difficulties Questionnaire Hyperactivity subscale (SDQ-H), and Strengths and Difficulties Questionnaire Emotional and Peer Problems subscale (SDQ-Int) were associated with an increased fracture risk (Odds Ratio [OR] (95% Confidence Interval [CI]): 1.15 (1.05-1.27), OR: 1.05 (1.01-1.09), OR: 1.25 (1.01-1.54), and OR: 1.19 (1.04-1.37), respectively). The AQ-C and SDQ-Int scales remained statistically significant as risk factors for upper ex-tremity fractures (OR: 1.15 (1.02-1.28) and OR: 1.21 (1.02-1.43), respectively) in the multivariate regression analyses. CONCLUSION: Our findings suggest that psychological factors affecting both parents and children could potentially increase the risk of upper extremity fractures in preschool children.

Phytoremediation potential of Brassica oleracea varieties through cadmium tolerance gene expression analysis.

BACKGROUND: Brassica oleracea var. acephala, commonly referred to as kale, is a well-documented plant species, a food crop but well recognized for its capacity to endure and manage the accumulation of heavy metals. In this research, the phytoremediation potential of kale was evaluated based on cadmium intake, utilizing three distinct kale varieties originating from Bosnia and Herzegovina. All kales were grown in controlled conditions, with different concentrations of cadmium (Cd), a known strong pollutant found in small concentrations in soil under normal environmental conditions. After the root length analysis and cadmium atomic spectrometry, we utilized quantitative PCR (qPCR) and cycle threshold (Ct) values to calculate the expression levels of five genes associated with Cd heavy metal response: Mitogen-activated protein kinase 2 (MAPK2), Farnesylated protein 26 and 27 (HIPP26, HIPP27), Natural resistance-associated macrophage protein 6 (RAMP6), and Heavy metal accumulator 2 (HMA2). RESULTS: The atomic reader's analysis of rising cadmium concentrations revealed a proportional decline in the length of kale roots. The gene expression levels corresponded to cadmium stress differently among varieties, but mostly showing notable up-regulations under Cd stress, indicating the strong Cd presence within the plant. CONCLUSIONS: This study demonstrated differences in gene expression behavior among three B. oleracea varieties from Bosnia and Herzegovina, indicating and filtering the Cd-resistant kale, and kale varieties suitable for phytoremediation. For the first time, such a study was conducted on kale varieties from Bosnia and Herzegovina, analyzing the impact of cadmium on the growth and resilience of these species.

The role of the psychological attributes of parents and children, and fracture history in upper extremity fractures in school-age and adolescents: A case-control study.

OBJECTIVES: This study aims to investigate the influence of parents and children's psychological attributes and previous fracture history on upper extremity fractures in school-aged and adolescent children. PATIENTS AND METHODS: Between January 2022 and January 2023, a total of 194 participants consisting of 97 cases with upper extremity fractures (23 males, 74 females; median age: 10 years; range, 6 to 16 years) and 97 age-matched controls suffering from growing pains (47 males, 50 females; median age: 10 years; range, 6 to 16 years) were included in this case-control study. Both cases and controls were of school-age or over. The parents of the children were interviewed face-to-face using psychological scales including the Adult Attention Deficit Hyperactivity Disorder Self-Report Scale (ASRS), the Autism-Spectrum Quotient (AQ), the Short Form of the Conners' Parent Rating Scale-Revised (CPRS-R:S), and the Developmental Coordination Disorder Questionnaire 2007 (DCDQ'07). The results derived from these scales and the demographics of the participants were evaluated in terms of their association with the risk of upper extremity fractures. RESULTS: A household income below the official minimum monthly wage (MMW) and a previous fracture history showed a higher risk for upper extremity fractures (odds ratio [OR]=2.38, 95% confidence interval [CI]: 1.07-5.26 and OR=24.93, 95% CI: 3.27-189.98, respectively). In the univariate analyses, elevated scores on the hyperactivity subscale of CPRS-R:S (CPRS-R:SHS) were associated with a higher fracture risk (OR=1.14, 95% CI: 1.05-1.24). Furthermore, both a household income below MMW, a previous fracture history, and higher CPRS-R:S-HS scores were found as independent risk factors for upper extremity fractures in the multivariate regression analysis (OR=2.78, 95% CI: 1.13-6.86, OR=21.79, 95% CI: 2.73-174.03), and OR=1.11, 95% CI: 1.02-1.22, respectively). CONCLUSION: Our study results highlight the importance of known risk factors for upper extremity fractures such as lower monthly wage and the presence of previous fractures. The psychological states of parents and children should be evaluated together.

Understanding and overcoming resistance to immunotherapy in genitourinary cancers.

The introduction of novel immunotherapies has significantly transformed the treatment landscape of genitourinary (GU) cancers, even becoming the standard of care in some settings. One such type of immunotherapy, immune checkpoint inhibitors (ICIs) like nivolumab, ipilimumab, pembrolizumab, and atezolizumab play a pivotal role by disturbing signaling pathways that limit the immune system's ability to fight tumor cells. Despite the profound impact of these treatments, not all tumors are responsive. Recent research efforts have been focused on understanding how cancer cells manage to evade the immune response and identifying the possible mechanisms behind resistance to immunotherapy. In response, ICIs are being combined with other treatments to reduce resistance and attack cancer cells through multiple cellular pathways. Additionally, novel, targeted strategies are currently being investigated to develop innovative methods of overcoming resistance and treatment failure. This article presents a comprehensive overview of the mechanisms of immunotherapy resistance in GU cancers as currently described in the literature. It explores studies that have identified genetic markers, cytokines, and proteins that may predict resistance or response to immunotherapy. Additionally, we review current efforts to overcome this resistance, which include combination ICIs and sequential therapies, novel insights into the host immune profile, and new targeted therapies. Various approaches that combine immunotherapy with chemotherapy, targeted therapy, vaccines, and radiation have been studied in an effort to more effectively overcome resistance to immunotherapy. While each of these combination therapies has shown some efficacy in clinical trials, a deeper understanding of the immune system's role underscores the potential of novel targeted therapies as a particularly promising area of current research. Currently, several targeted agents are in development, along with the identification of key immune mediators involved in immunotherapy resistance. Further research is necessary to identify predictors of response.

Immunotherapy has transformed the treatment landscape for many cancer types, including genitourinary malignancies such as renal and bladder cancers.However, not all patients or tumor types, such as prostate cancer, respond to this type of treatment.Understanding the mechanisms of immunotherapy resistance is critical for developing strategies to overcome these challenges.Primary resistance, which is present at the onset of treatment, can bedue to genetic abnormalities or immune system dysregulation. These factors alter the interactions between host cells and cancer cells.Adaptive resistance develops during therapy due to dynamic changes in the levels of growth factors, cytokines, and the tumor microenvironment (TME).Acquired resistance mainly occurs at the genetic and translational levels, involving the downregulation of critical human leukocyte antigen (HLA) molecules and interference with mutational repair.Future therapies may focus on detailed genetic profiling of patients to guide treatment selection and on the use of immune profile monitoring to assist in assessing responsiveness, alongside developing novel targeted therapies and ICIs.Further research is needed to identify predictors of response to ICIs.

HIIT serves as an efficient training strategy for basketball players by improving blood fluidity and decreasing oxidative stress.

BACKGROUND: A challenge for coaches and athletes is to find the best combination of exercises during training. Considering its favorable effects, HIIT has been very popular recently. OBJECTIVE: The goal of this study was to investigate anthropometric features, performance, erythrocyte deformability, plasma viscosity (PV) and oxidative stress in response to acute and long-term (6 weeks) HIIT in adolescent basketball players. METHODS: 22 sportsmen between the ages of 14-16 were included. Tabata protocol was applied to the HIIT group in addition to their routine training program 3 days/week, for 6 weeks. Erythrocyte deformability was determined using an ectacytometer (LORCA), PV with a rotational viscometer. Total oxidant status (TOS), total antioxidant status (TAS) were measured by kits. RESULTS: HIIT for 6 weeks induced an improvement in performance tests and waist circumference. 6 weeks of HIIT resulted in a decrement, while the last exercise session yielded an increment in RBC deformability. PV and TOS of HIIT groups were decreased on the 6th week. CONCLUSIONS: Our results demonstrate that, HIIT in addition to the routine exercise program is beneficial for improving performance and blood fluidity as well as decreasing oxidative stress in basketball players. Therefore, HIIT seems as an efficient training strategy for highly-trained individuals.

What factors are associated with osteoarthritis after cementation for benign aggressive bone tumor of the knee joint: a systematic review and meta-analysis.

Background: The current systematic review aimed to answer the following questions: (i) Does extended curettage combined with the PMMA technique for the treatment of aggressive bone tumors around the knee led to the development of knee osteoarthritis? (ii) What factors are associated with osteoarthritis after bone cementation around the knee joint? Methods: This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All electronic searches were performed on November 20, 2022, by a single researcher who evaluated the full texts of potentially eligible studies to determine inclusion. In these patients, the presence of osteoarthritis secondary to the surgical procedure was investigated. Data extracted included study type, characteristics of participants, sample size, gender, tumor site (femur or tibia), secondary osteoarthritis, tumor volume, distance from the joint cartilage, reoperation, follow-up time, Campanacci grade, and pathological fracture. Results: In total, 11 studies comprising 204 patients were evaluated, and it was found that 61 (30%) patients developed knee osteoarthritis due to extensive curettage and bone cement application for benign aggressive tumor treatment. According to the results obtained based the random effects model with the 11 studies included in the meta-analysis, the mean odds ratio of development knee OA with the 95% CI was calculated as -2.77 (-3.711, -1.83), which was statistically significant (z = -5.79; P < 0.000). Conclusion: The association of distance between the tumor and joint cartilage and development of osteoarthritis was not shown in this meta-analysis. Level of Evidence: Level IV prognostic study.

Effectiveness of gonarthrosis treatment via intra-articular injections of linear vs. cross-linked hyaluronic acids.

OBJECTIVES: The study aimed to compare the outcomes of single-dose cross-linked hyaluronic acid and the linear regimen of three doses of HA knee injections among patients with gonarthrosis. PATIENTS AND METHODS: This single-center, retrospective study was conducted with 60 patients (47 females, 13 males; mean age: 57.9±4.29 years; range, 50 to 65 years) with Kellgren-Lawrence Grade 2 or 3 gonarthrosis between February 2020 and February 2022. Patients were either subjected to intra-articular cross-linked hyaluronic acid (n=30) or linear hyaluronic acid (n=30) injection treatments. Comprehensive assessments of the patients were conducted prior to the injections, as well as at three and six months after injection. The two injection groups were compared regarding the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Oxford Knee Score. RESULTS: Both injections showed a statistically significant improvement from baseline in both WOMAC and Oxford Knee Score at three and six months (p<0.001). There was no notable distinction in the alteration of WOMAC knee scores between the two injection types. However, a notable discrepancy was observed in the elevation of Oxford Knee Score among patients who received cross-linked knee injections compared to those who underwent linear hyaluronic acid knee injections, signifying a significant increase in the former group (p<0.001). CONCLUSION: The advantage of a single-dose administration of cross-linked HA knee injections, as opposed to the three-dose regimen required for linear hyaluronic acid, translates into reduced time and cost for the injection process. Moreover, this approach minimizes injection-associated discomfort for patients due to the singular dose administration.

Unpleasant Souvenir: Imported Plasmodium falciparum Malaria in Türkiye.

Objective: Each year, approximately 125 million people visit malaria-endemic countries. This study aimed to investigate the clinical characteristics of imported Plasmodium falciparum malaria infections in Türkiye. Methods: The study included patients diagnosed with P. falciparum malaria between 1996 and 2022. A retrospective evaluation was conducted on whole blood samples and/or blood smears, as well as detailed medical histories, clinical manifestations, and laboratory findings. A total of 131 imported cases of P. falciparum were included in the study. Results: Among the patients, 121 were male. Of these, 101 had traveled to Africa, while 30 had visited Asia. Among the patients, 109 were returned travelers, and 22 were refugees/migrants. Early trophozoites were observed in all patients, while gametocytes were detected in 30 patients. Cerebral malaria developed in 15 patients, resulting in the death of two individuals. Additionally, 10 patients received preventive chemoprophylaxis. Conclusion: Turkey is situated on migration routes that connect two continents to Europe, where more than 95% of the global malaria burden exists. The importation of malaria through returned travelers poses a risk of malaria reintroduction in our country, given the presence of suitable vectors, climate conditions, and environmental factors. Importantly, 30 patients (22.9%) exhibited gametocyte forms of P. falciparum, which have the potential to infect Anopheles species, thus establishing a basis for local malaria transmission.

The importance of inflammatory biomarkers in ischemic stroke patients with carotid artery stenosis.

OBJECTIVE: This study aims to investigate inflammatory markers and their relationship with the degree of stenosis in ischemic stroke patients with carotid artery stenosis. METHODS: This retrospective case-control study was conducted with 70 newly diagnosed ischemic stroke patients and 70 age- and gender-matched healthy controls. Laboratory analyses were carried out including serum hemogram, biochemistry profiles, erythrocyte sedimentation rate, and C-reactive protein (CRP). Mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-high-density lipoprotein cholesterol ratio (MHR) values were calculated, and compared between the patients and healthy controls. Patients were divided into two groups according to the degree of arterial carotid stenosis. The degree of carotid stenosis was <50% in Group 1 and it was 50% and above in Group 2. RESULTS: In the patient group, neutrophil, monocyte, MPV, CRP, sedimentation, MHR, PLR, and NLR levels were significantly higher than the control group. There was no significant correlation between the level of carotid stenosis and inflammatory biomarkers. There was a significant correlation between the presentation NIHSS value and CRP, PLR, and NLR values. CONCLUSION: Inflammatory biomarker values were higher in stroke patients with carotid artery stenosis than in healthy individuals. However, they should neither be used to predict the degree of carotid artery stenosis.

Coronal plane growth modulation for genu valgum in skeletal dysplasia / Modulação do crescimento do plano coronal para genu valgum na displasia esquelética

ABSTRACT Objective: To investigate the efficiency and rates of correction by hemiepiphysiodesis using 8-plate to manage genu valgum deformity in children with skeletal dysplasia. Methods: Eleven children with skeletal dysplasia (three female, eight male; mean age = 10.5 years; age range = 7-13) who underwent temporary hemiepiphysiodesis using 8-plates for genu valgum deformity were retrospectively reviewed. There were nine bilateral cases and two unilateral cases. The mean follow-up time from the index surgery to the final follow-up was 45 (ranging from 24 to 72) months. Radiographical assessment including preoperative and final follow-up measurements of joint orientation angles and mechanical axis deviation (MAD) were conducted. Results: Deformities were completely corrected in nine lower extremities (45%) and partially corrected in seven extremities (35%). In four extremities of two children with Morquio syndrome, MAD worsened. The correction rate of MAD was 1.25 ± 1.62 mm/mo. Conclusion: Though hemiepiphysiodesis using 8-plate requires a longer treatment period, it seems to be an effective treatment for correction of genu valgum in children with skeletal dysplasia. Level of Evidence IV, Case Series.

RESUMO Objetivo: Investigar a eficiência e as taxas de correção da hemiepifisiodese usando placa-8 no tratamento da deformidade de geno valgo em crianças com displasia esquelética. Métodos: Foram avaliadas retrospectivamente 11 crianças com displasia esquelética (três meninas e oito meninos; idade média = 10,5 anos; faixa etária = 7-13) que foram submetidas à hemiepifisiodese temporária com placa-8 devido à deformidade do geno valgo. Havia nove casos bilaterais e dois casos unilaterais. O acompanhamento médio desde a cirurgia de implante até o acompanhamento final foi de 45 (variação de 24 a 72) meses. Foi feita avaliação radiográfica incluindo medidas de acompanhamento pré e pós-operatórias dos ângulos de orientação da articulação e desvio mecânico do eixo (MAD). Resultados: As deformidades foram completamente corrigidas em nove extremidades inferiores (45%) e parcialmente corrigidas em sete (35%). Em quatro extremidades de duas crianças com síndrome de Morquio, o MAD piorou. A taxa de correção do MAD foi de 1,25 ± 1,62 mm/mês. Conclusão: Embora a hemiepifisiodese com placa-8 necessite de um período de tratamento mais longo, a técnica parece ser um tratamento eficaz para a correção do geno valgo em crianças com displasia esquelética. Nível de Evidência IV, Série de Casos.

Ultrasound-guided adductor canal block using levobupivacaine versus periarticular levobupivacaine infiltration after totalknee arthroplasty: a randomized clinical trial

ABSTRACT BACKGROUND: Both postoperative pain control and range of motion are important in total knee arthroplasty (TKA). However, in the literature, there is little comparison of peripheral nerve blocks and periarticular infiltration techniques using levobupivacaine. The aim of our study was to measure pain with visual analogue scale (VAS) and knee range of motion (ROM) between in patients undergoing adductor canal block (ACB) for TKA using levobupivacaine compared to periarticular levobupivacaine infiltration (PAI-L). DESIGN AND SETTING: Prospective randomized clinical trial in a university hospital. METHODS: Patients aged 40-85 years who underwent unilateral TKA were included; 39 were treated withperiarticular infiltration using 40 ml (0.125 mg) of levobupivacaine (PAI-L group); and 40 were treated with ACB using 20 ml of 0.25% levobupivacaine (ACB-L group). Postoperative pain scores at rest and during active physical therapy were assessed using a VAS, along with knee ROM in flexion and extension. In addition, 100-foot walking time results, total morphine consumption and time of first analgesia requirement were recorded postoperatively. RESULTS: VAS scores at rest and during active physical therapy and the total amount of morphine consumed were lower in the ACB-L group than in the PAI-L group (P < 0.05). In contrast, knee ROM in flexion and extension and 100-foot walking times were greater in the PAI-L group than in the ACB-L group (P < 0.05). CONCLUSION: ACB-L was superior to PAI-L regarding pain treatment after TKA; however, PAI-L was superior to ACB-L regarding postoperative ROM and walking ability. CLINICAL TRIAL REGISTRY: ACTRN-12618000438257.

The effect of prophylactic dose of a low molecular weight heparin on skin wound healing of rats / Efeito da dose profilática de heparina de baixo peso molecular na cicatrização de feridas na pele de ratos

PURPOSE: To investigate the effect of prophylactic dose of a low molecular weight heparin, enoxaparin, on skin wound healing of rats. METHODS: Forty rats were used for the study. Rats were randomly assigned to two equal groups. Experimental group received prophylactic dose of enoxaparin. Physiologic saline was administered to the control group. Parameters of wound healing of experimental and control groups were compared. For comparison of the groups in terms of fibrosis, vascularization, inflammation, epithelization, and tensile strength test (Newton). Mann-Whitney-U test was used because variables were categorical data (fibrosis, vascularization, inflammation and epithelization). Differences between groups were analyzed with independent samples t-test (tensile strength). Significance was set at p<0.05. RESULTS: Skin wound of the experimental group presented tensile strength significantly decreased (p<0.001), histopathologic examination revealed a significant (p<0.001) delayed epithelization and decreased in fibrosis, vascularization, inflammation (p<0.001) in the experimental group. CONCLUSION: Enoxaparin delay wound healing by decreased inflammatory cells, fibroblast contents and their products (growth factors), and by promoted hemorrhage.

OBJETIVO: Investigar o efeito de dose profilática da heparina de baixo peso molecular, enoxaparina, na cicatrização de feridas na pele de ratos. MÉTODOS: Quarenta ratos foram utilizados para o estudo. Ratos foram distribuídos aleatoriamente a dois grupos iguais. O grupo experimental recebeu profilática de enoxaparina. Solução salina fisiologica foi administrada ao grupo controle. Foram comparados parâmetros de cicatrização dos grupos experimental e controle.Os grupos foram comparados em termos de fibrose, vascularização, inflamação, epitelização e força tensil (teste de Newton). Foi realizado o teste de Mann-Whitney-U para variáveis com dados categóricos (fibrose, cicatrização, inflamação e epitelização). Diferenças entre os grupos foram analisadas como amostras independentes pelo t-teste (força tensil). Significância foi fixada para p < 0,05. RESULTADOS: A ferida do grupo experimental apresentou força tensil diminuída significativamente (p < 0,001), o exame histopatológico revelou um significativo (p < 0,001) retardo na epitelização e diminuição na fibrose, cicatrização, inflamação (p < 0,001) no grupo experimental. CONCLUSÃO: A enoxaparina retarda a cicatrização da ferida pela diminuição das células inflamatórias, pelo menor conteúdo de fibroblasto e seus produtos (fatores de crescimento) e por promover hemorragia. O grupo experimental foi incluído pela perda significativa da força tênsil no presente estudo.

O polimorfismo VNTR no gene codificador do antagonista do receptor da interleucina-1 está associado com a doença arterial coronariana / Interleukin-1 receptor antagonist gene VNTR polymorphism is associated with coronary artery disease

FUNDAMENTO: A Doença Arterial Coronariana (DAC) é a aterosclerose das artérias coronárias que transportam o sangue para o coração. A aterosclerose é uma doença inflamatória. As variações gênicas das citocinas - como as associadas à família IL1 - fazem parte da patogênese da aterosclerose. OBJETIVO: O objetivo deste estudo foi determinar a relação entre os polimorfismos da família IL1 (VNTR do IL1RN, posições -511 e +3953 do IL1B) e a DAC na população turca. MÉTODOS: Um total de 427 indivíduos foram submetidos à angiografia coronariana e em seguida divididos da seguinte forma: 170 no grupo controle e 257 no grupo de pacientes com DAC. Os sujeitos com DAC foram divididos em dois subgrupos: 91 no grupo de Doença Coronariana em um único vaso (Single Vessel Disease - SVD) e 166 no grupo Doença Coronariana em múltiplos vasos (Multiple Vessel Disease - MVD). Os genótipos de IL1RN e IL1B (-511, +3953) foram determinados por reação em cadeia da polimerase (RCP), seguida de análise da digestão por enzima de restrição. RESULTADOS: Não foram observadas diferenças significantes nas distribuições de genótipos de IL1RN e IL1B (-511 e +3953) entre os sujeitos com DAC e os controles, ou entre sujeitos com MVD e controles. No entanto, observou-se uma relação significante no genótipo IL1RN 2/2 entre sujeitos portadores de SVD e controles (P= 0,016, x2: 10,289, OR: 2,94IC 95 por cento 1,183 - 7,229). Tampouco foi observada diferença estatisticamente significante nas freqüências dos alelos de IL1RN e IL1B (-511 e +3953) entre os sujeitos com DAC e controles, os sujeitos com MVD e controles, ou ainda os sujeitos SVD e controles. CONCLUSÃO: Não foi observada nenhuma relação na freqüência alélica e nem na distribuição genotípica dos polimorfismos de IL1RN e IL1B entre sujeitos com DAC e grupos controle. No entanto, o genótipo IL1RN 2/2 pode representar um fator de risco para sujeitos com SVD na população turca.

BACKGROUND: Coronary Artery Disease (CAD) is the atherosclerosis of coronary arteries that carry blood to the heart muscle. Atherosclerosis is an inflammatory disease. Cytokine gene variations such as those associated with the IL1 family are involved in the pathogenesis of atherosclerosis. OBJECTIVE: The purpose of this study was to determine the relationship between IL1 family polymorphisms (IL1RN VNTR, IL1B positions -511 and +3953) and CAD in Turkish population. METHODS: 427 individuals were submitted to coronary angiography and were grouped as 170 control subjects and 257 CAD patients. The CAD subjects were divided into two subgroups: 91 Single Vessel Disease (SVD) and 166 Multiple Vessel Disease (MVD) subjects. The genotypes of IL1RN and of IL1B (-511, +3953) were determined by polymerase chain reaction (PCR) followed by restriction digestion analysis. RESULTS: No significant difference was found in IL1RN and IL1B (-511 and +3953) genotype distributions between CAD and control subjects or MVD and control subjects. However, significant association was seen in IL1RN 2/2 genotype between SVD and control subjects (P= 0.016, x2: 10.289, OR: 2.94, 95 percent CI: 1.183-7.229). Similarly, no statistically significant difference was found in IL1RN and IL1B (-511 and +3953) allele frequencies between CAD and control subjects, MVD and control subjects or SVD and control subjects. CONCLUSION: No association was found in either allele frequency or genotype distribution of IL1RN and IL1B polymorphisms between CAD and the control groups. However; IL1RN 2/2 genotype may be a risk factor for SVD in the Turkish population.