RESUMO
OBJECTIVE: Highly active antiretroviral therapy (HAART) has considerably reduced HIV/AIDS-related morbidity and mortality; however, the therapy has been associated with the development of cardiovascular disease (CVD), and genetic predisposition factors may aggravate disease outcome. This study was aimed at investigating the relationship between haptoglobin phenotypes and risk factors of CVD in HIV patients. METHODS: A total of 105 HIV sero-positive patients on HAART and 75 HIV-infected HAART-naïve individuals were enrolled in the study. Socio-demographics and clinical characteristics of the participants were obtained using a well-structured questionnaire. Lipid profile, lactate dehydrogenase (LDH) and haptoglobin (Hp) phenotypes were analysed from serum whiles haemoglobin (Hb) level, CD4+ cell count and HIV viral RNA load were determined using whole blood. RESULTS: Atherogenic index of plasma (AIP) was significantly higher in patients on HAART than the naïve group (P < 0.05). Age, BMI, visceral fat, systolic blood pressure LDH and lipid variables strongly and positively correlated with AIP (P < 0.05), with the exception of HDL-c (P < 0.001) which showed a negative correlation. HAART was associated with hypertension (χ2 = 4.33, P = 0.037), hypercholesterolaemia (χ2 = 10.99, P < 0.001), elevated LDL-c (χ2 = 10.30, P < 0.001) and decreased HDL-c (χ2 = 3.87, P = 0.09). Hp2-2 and Hp0 collectively was strongly associated with hypertension (OR = 2.54, P = 0.011), obesity (OR = 5.97, P < 0.001) and hypercholesterolaemia (OR = 2.99, P < 0.001). CONCLUSION: HIV/AIDS patients on HAART expressing Hp phenotypes with weak antioxidant capacity have an increased risk of developing CVD.
OBJECTIF: La thérapie antirétrovirale hautement active (HAART) a considérablement réduit la morbidité et la mortalité liées au VIH/SIDA; cependant, le traitement a été associé au développement de maladie cardiovasculaire (MCV) et des facteurs de prédisposition génétique pourraient aggraver l'évolution de la maladie. Cette étude visait à étudier la relation entre les phénotypes de l'haptoglobine et les facteurs de risque de MCV chez les patients VIH. MÉTHODES: Un total de 105 patients VIH positifs sous HAART et 75 personnes infectés par le VIH mais naïfs au HAART ont été recrutés pour l'étude. Les caractéristiques sociodémographiques et cliniques des participants ont été obtenues à l'aide d'un questionnaire bien structuré. Le profil lipidique, les phénotypes de la lactate déshydrogénase (LDH) et de l' haptoglobine (Hp) ont été analysés à partir du sérum tandis que le taux d'hémoglobine (Hb), la numération des cellules CD4+ et la charge d'ARN viral du VIH ont été déterminés en utilisant du sang total. RÉSULTATS: L'indice athérogène du plasma (IAP) était significativement plus élevé chez les patients sous HAART que chez le groupe naïf (p <0,05). Les variables âge, IMC, graisse viscérale, tension artérielle systolique, LDH et lipides étaient fortement et positivement corrélées à l'IAP (p < 0,05), à l'exception du HDL-c (p < 0,001) qui présentait une corrélation négative. L'HAART a été associée à l'hypertension (χ2 = 4,33; p = 0,037), l'hypercholestérolémie (χ2 = 10,99; p <0,001), une LDL-c élevée (χ2 = 10,30; p <0,001) et une diminution de HDL-c (χ2 = 3,87; p = 0,09). Ensemble, Hp2-2 et Hp0 étaient fortement associés à l'hypertension (OR = 2,54; p = 0,011), à l'obésité (OR = 5,97; p <0,001) et à l'hypercholestérolémie (OR = 2,99; p <0,001). CONCLUSION: Les patients VIH/SIDA sous HAART exprimant des phénotypes Hp à faible capacité antioxydante ont un risque accru de développer une maladie cardiovasculaire.
Assuntos
Antioxidantes/análise , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Infecções por HIV/tratamento farmacológico , Haptoglobinas/análise , Adulto , Aterosclerose/sangue , Aterosclerose/epidemiologia , Doenças Cardiovasculares/sangue , Estudos de Casos e Controles , Estudos Transversais , Feminino , Gana , Infecções por HIV/sangue , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/epidemiologia , Hipertensão/sangue , Hipertensão/epidemiologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Fenótipo , Medição de Risco , Fatores de RiscoRESUMO
People living with HIV (PLWH) usually suffer from co-infections and co-morbidities including respiratory tract infections. SARS-CoV-2 has been reported to cause respiratory infections. There are uncertainties in the disease severity and immunological response among PLWH who are co-infected with COVID-19. This review outlines the current knowledge on the clinical outcomes and immunological response to SARS-CoV-2 among PLWH. Literature was searched in Google scholar, Scopus, PubMed, and Science Direct conforming with the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines from studies published from January 2020 to June 2023. A total of 81 studies from 25 countries were identified, and RT-PCR was used in confirming COVID-19 in 80 of the studies. Fifty-seven studies assessed risk factors and clinical outcomes in HIV patients co-infected with COVID-19. Thirty-nine of the studies indicated the following factors being associated with severe outcomes in HIV/SARS-CoV-2: older age, the male sex, African American race, smoking, obesity, cardiovascular diseases, low CD4+ count, high viral load, tuberculosis, high levels of inflammatory markers, chronic kidney disease, hypertension, diabetes, interruption, and delayed initiation of ART. The severe outcomes are patients' hospitalization, admission at intensive care unit, mechanical ventilation, and death. Twenty (20) studies, however, reported no difference in clinical presentation among co-infected compared to mono-infected individuals. Immune response to SARS-CoV-2 infection was investigated in 25 studies, with some of the studies reporting high levels of inflammatory markers, T cell exhaustion and lower positive conversion rate of IgG in PLWH. There is scanty information on the cytokines that predisposes to severity among HIV/SARS-CoV-2 co-infected individuals on combined ART. More research work should be carried out to validate co-infection-related cytokines and/or immune markers to SARS-CoV-2 among PLWH.
Assuntos
COVID-19 , Infecções por HIV , Humanos , COVID-19/imunologia , Citocinas , Infecções por HIV/complicaçõesRESUMO
Gastric cancer (GC) prevalence is on the increase in Ghana, and Epstein-Barr virus (EBV) is one of the factors that have been implicated in the etiology of the cancer. It is therefore important to know the contribution of EBV genotype and strains that are associated with GC. In this study, we aimed at genotyping EBV and determining predominant strains in GC biopsies in Ghanaian patients. Genomic DNA was extracted from 55 GC biopsies (cases) and 63 normal gastric tissues (controls) were amplified by polymerase chain reaction (PCR) using specific primers for EBV detection and genotyping followed by PCR fragments sequencing. Epstein-Barr virus positivity were 67.3% and 49.2% in the GC and normal biopsies, respectively. Both cases and controls had the Mediterranean + strain of EBV. The predominant genotype of the virus in the GC cases was genotype-1 (75.7%) compared to 66.7% of genotype-2 among the control group. Infection was associated with GC in the study population (OR = 2.11, P = 0.014, 95% CI: 1.19 - 3.75), and EBV genotype-1 significantly increased the risk of GC (OR = 5.88, P < 0.0001, 95% CI: 3.18-10.88). The mean EBV load in the cases (3.507 ± 0.574) was significantly higher than in the controls (2.256 ± 0.756) (P < 0.0001). We conclude that EBV, especially Mediterranean + genotype-1, was the predominant strain in GC biopsies and GC type or progression is independent of the viral load.
Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Humanos , Herpesvirus Humano 4/genética , Gana/epidemiologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Biópsia , GenótipoRESUMO
Preeclampsia increases the risk of pregnancy-related complications, nevertheless a successful spiral vessel remodeling, and trophoblast invasion reduces disorders of pregnancy. Matrix metalloproteinase-2 (MMP-2) clears the path for trophoblast invasion, and activation of MMP-2 largely depends on extracellular matrix metalloproteinases inducer (EMMPRIN) protein. This study aimed to investigate EMMPRIN gene polymorphism and MMP-2 activity in preeclampsia patients. Archival whole blood and serum samples of 74 preeclampsia and 66 normotensive pregnant women age-matched were used in this case-control study. Genomic DNA was extracted from the whole blood samples and EMMPRIN gene amplified with specific primers following fragments sequence mutation analysis. Serum MMP-2 activity was determined using enzyme-linked immunosorbent assay (ELISA) and socio-demographic data of participants retrieved from the database. Age of preeclampsia patients (32.78 ± 6.39) years and body mass index (BMI) (33.09 ± 7.27) kg/m2 compared with the normotensive counterparts (32.33 ± 5.56) years and (32.33 ± 5.56) kg/m2,respectively, were not statistically significant (P > 0.05). Serum matrix metalloprotease-2 (MMP-2) activity was significantly reduced in preeclampsia group (16.34 ± 7.07) compared with the normotensives (25.63 ± 4.56) (P < 0.001), and rs424243T/G variant (55.6%) was overrepresented among the cases compared with the normotensives (16.7%). The single-nucleotide polymorphism T/G was found to be associated with preeclampsia (odds ratio [OR] = 7.63; 95% confidence interval [CI] = 3.95-14.75; P < 0.0001). Decreased activity of MMP-2 and rs424243T/G SNP of EMMPRIN gene was reported in preeclampsia. These preliminary data warrant a further investigation into the relationship between EMMPRIN gene polymorphism and MMP-2 activity in preeclampsia.
Assuntos
Basigina , Pré-Eclâmpsia , Adulto , Feminino , Humanos , Gravidez , Basigina/genética , Basigina/metabolismo , Estudos de Casos e Controles , Matriz Extracelular/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Polimorfismo Genético , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismoRESUMO
Introduction: breast cancer development is linked to mutant single nucleotide polymorphism of breast cancer type 1 (BRCA1) gene usually harboured within exon 11. It has also been linked to finger dermatoglyphics where certain patterns have been associated with breast cancer. This study suggests a possible relationship between finger dermatoglyphic patterns and single nucleotide polymorphism of BRCA1 gene. Methods: in a quantitative cross-sectional approach, finger dermatoglyphic patterns were obtained using the ink method from 70 female breast cancer patients and 70 age-matched apparently healthy females. Approximately 5 ml of venous blood was obtained from each participant from which DNA was extracted from the white blood cells collected after centrifugation. DNA was amplified and sequenced and the data aligned with the wildtype template of BRCA1 gene. Fingerprint patterns were analyzed with Chi-square. Mean frequency of fingerprint patterns was analyzed with independent student's t-test. Differences in data set with p<0.05 were statistically significant. Results: luminal B was the predominant breast cancer molecular subtype among the patients. The predominant fingerprint pattern among breast cancer participants was the loop. Six or more loops had higher frequency among breast cancer females. The predominant BRCA1 gene variant locations were c.34311, c.34320, and c.34321 with c.34311A>C being the predominant variant. Higher percentage frequency of six or more loops in relation to c.34311A>C was observed in apparently healthy females compared to breast cancer females. Conclusion: the study reports for the very first time in Ghana, BRCA1 gene variants and finger dermatoglyphics among breast cancer patients. Although the results are preliminary and inconclusive it creates an avenue for extended studies.
Assuntos
Neoplasias da Mama , Genes BRCA1 , Humanos , Feminino , Gana , Neoplasias da Mama/genética , Dermatoglifia , Polimorfismo de Nucleotídeo Único , Proteína BRCA1/genéticaRESUMO
Breast cancer is the most common malignancy in women, with alarming mortalities. Neoadjuvant treatments employ chemotherapy to shrink tumours to a well-defined size for a better surgical outcome. The current means of assessing effectiveness of chemotherapy management are imprecise. We previously showed that breast cancer patients have higher serum circulating cell-free DNA concentrations. cfDNA is degraded cellular DNA fragments released into the bloodstream. We further report on the utility of cfDNA in assessing the response to chemotherapy and its potential as a monitoring biomarker. A total of 32 newly diagnosed and treatment-naive female breast cancer patients and 32 healthy females as controls were included. Anthropometric, demographic and clinicopathological information of participants were recorded. Each participant donated 5 mL of venous blood from which sera were separated. Blood sampling was carried out before the commencement of chemotherapy (timepoint 1) and after the third cycle of chemotherapy (timepoint 2). qPCR was performed on the sera to quantify ALU 115 and 247 levels, and DNA integrity (ALU247/ALU115) was determined. ALU 115 and 247 levels were elevated in cancer patients but were significantly decreased after the third cycle of chemotherapy (T2) compared to T1. DNA integrity increased after the third cycle. Serum cfDNA may provide a relatively inexpensive and minimally invasive procedure to evaluate the response to chemotherapy in breast cancer.
Assuntos
Neoplasias da Mama , Ácidos Nucleicos Livres , Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , DNA , Feminino , Humanos , Terapia NeoadjuvanteRESUMO
Nasopharyngeal cancer (NPC) is associated with Epstein Barr virus (EBV) infection. However different viral strains have been implicated in NPC worldwide. This study aimed to detect and characterize EBV in patients diagnosed with NPC in Ghana. A total of 55 patients diagnosed with NPC by CT scan and endoscopy were age-matched with 53 controls without a known oncological disease. Venous blood was collected from the study participants and DNA extracted from the blood samples. Detection of EBV and genotyping were done by amplifying Epstein Barr nuclear antigen 1 (EBNA-1) and Epstein Barr nuclear antigen 2 (EBNA-2), respectively, using specific primers. Viral load in patients and controls was determined using real-time polymerase chain reaction. EBV positivity in controls (92%) was significantly greater than that of NPC patients (67%) (χ2 = 19.17, p < 0.0001), and viral infection was independent of gender (χ2 = 1.770, p = 0.1834). The predominant EBV genotypes in patients and controls were genotype 2 (52%) and genotype 1 (62%), respectively. Median EBV load was significantly higher in NPC patients than the control group (p < 0.01). In summary, prevalence of EBV genotype 2 infection was higher in NPC patients than the control group. Assessment of EBV load may be used as a biomarker for the diagnosis of NPC.
Assuntos
Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/genética , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/virologia , Adulto , Estudos de Casos e Controles , DNA Viral/genética , Infecções por Vírus Epstein-Barr/virologia , Antígenos Nucleares do Vírus Epstein-Barr/genética , Feminino , Técnicas de Genotipagem , Gana , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/etiologia , Neoplasias Nasofaríngeas/etiologia , Reação em Cadeia da Polimerase , Reação em Cadeia da Polimerase em Tempo Real , Carga Viral , Proteínas Virais/genéticaRESUMO
BACKGROUND: Breast cancer is the commonest malignancy in women worldwide. It is estimated to affect approximately 1.5 million women annually and responsible for the greatest number of cancer-related mortalities among women. In 2018, breast cancer mortalities stood at 627,000 women representing approximately 15% of all cancer deaths among women. In Ghana, breast cancer is the second leading cause of cancer deaths, with an incidence of 2,900 cases annually; one of eight women with the disease die. This gives impetus to the fight for improved early detection, treatment, and/management. In this light, we investigated the potential of death-associated protein kinase 1 (DAPK1) as a biomarker for breast cancer. As a tumour suppressor, its expression is activated by several carcinogens to influence cellular pathways that result in apoptosis, autophagy, immune response, and proliferation. AIM: To investigate DAPK1 as a blood biomarker for breast cancer. METHODS: Blood samples of participants diagnosed with breast cancer and healthy controls were collected and processed to obtain serum. Information on age, treatment, diagnosis, and pathology numbers was retrieved from folders. Pathology numbers were used to retrieve breast tissue blocks of patients at the Department of Pathology of the KBTH. Tissue blocks were sectioned and immunohistochemically stained with anti-DAPK1 and counterstained with hematoxylin to determine the DAPK1 expression levels. DAKP1 levels in blood sera were quantified using a commercial anti-DAPK1 ELISA kit. Case and control group means were compared using one-way ANOVA and Chi-square test. Statistical significance was set at p ≤ 0.05. Results and Discussion. DAPK1 levels were higher in sera and breast tissues of breast cancer patients than controls. The augmented DAPK1 expression can be interpreted as a stress response survival mechanism to remediate ongoing deleterious events in the cells orchestrated by carcinogenesis. In the presence of abundant DAPK1, the proliferative power of cells (both cancerous and noncancerous) is increased. This may explain why high DAPK1 expression strongly associates with aggressive breast cancer phenotypes like the ER-negative breast cancers, especially the triple-negative breast cancers (TNBC) which are the most aggressive, fast-growing, and highly metastatic. CONCLUSION: DAPK1 is highly expressed in sera and breast tissues of breast cancer patients than nonbreast cancer participants. The elevated expression of DAKP1 in circulation rather than in breast tissues makes it a candidate for use as a blood biomarker and potential use as therapeutic target in drug development.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Proteínas Quinases Associadas com Morte Celular/sangue , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proteínas Quinases Associadas com Morte Celular/genética , Proteínas Quinases Associadas com Morte Celular/metabolismo , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Worldwide, approximately 257 million people have chronic hepatitis B virus (HBV) infection, with the highest infection rates recorded in Africa and Asia. Although HBV infection has been associated with dyslipidemia, which may lead to death via liver related complications, the effect of the virus on the lipid profile of patients remain unclear. This study was designed to evaluate the effect of chronic hepatitis B virus infection on lipid profile of sero-positive individuals from Ghana. METHODS: Blood samples were collected from chronic HBV infected patients who were recruited from the Korle-Bu Teaching Hospital, Accra, and HBV sero-negative healthy volunteers who were used as controls. Demographic and clinical data were obtained using a structured questionnaire. Blood pressure and body mass index were determined, and HBV profile markers and lipid profiles of the patients were determined using a commercially available kit and a chemistry analyzer, respectively. RESULTS: Triglycerides, low density lipoproteins (LDL), high density lipoproteins (HDL), very low density lipoproteins (VLDL), and total cholesterol were used as indices of lipid metabolism disorder. Body mass index and diastolic blood pressures were significantly elevated in patients compared to healthy volunteers. CONCLUSION: The observed high total cholesterol and LDL, with a significantly lower HDL levels compared to healthy controls suggest an increased cardiovascular disease risk index in the patients. There is therefore the need to regularly monitor HBV infected patients for signs of cardiovascular diseases.
RESUMO
Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) have been associated with high oxidative stress in HIV patients. The disparity in antioxidant-oxidant levels in HIV patients favours viral replication and disease progression. This study aimed at determining the effect of ART on antioxidant enzymes activities and trace elements levels in Ghanaian HIV patients. A total of 242 participants; comprising of 105 HIV-infected patients on ART, 77 HIV-infected ART-naïve, and 60 HIV seronegative controls were recruited for the study. Whole blood was collected and used for haematological profiling, and the determination of CD4+ counts, superoxide dismutase (SOD) activity and trace element levels. Serum was used for liver function tests and the determination of glutathione reductase (GR) activity, and plasma was used to estimate reduced glutathione (GSH) levels. Low levels of haemoglobin (HB), hematocrit, mean cell volume (MCV) and mean cell hemoglobin (MCH), and trace elements were found in ART-naïve patients compared to those on ART and the seronegative controls. In the ART-naïve patients, glutathione reductase (GR) activity and reduced glutathione (GSH) level were significantly low compared to patients on ART and seronegative controls. Activity of SOD was significantly reduced in ART-naïve patients compared to those on ART and the control group, and manganese is the only trace element that showed a strong negative correlation with SOD activity and a positive and significant correlation with CD4+ count, and therefore needs to be investigated further. The study suggests that assessing antioxidant levels or enzymes activities of patients infected with HIV should be considered during therapy.
Assuntos
Antioxidantes/metabolismo , Glutationa Peroxidase/sangue , Glutationa Redutase/sangue , Infecções por HIV/sangue , Superóxido Dismutase/sangue , Oligoelementos/sangue , Adulto , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Feminino , Gana/epidemiologia , Glutationa/sangue , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , HIV , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/metabolismo , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Superóxido Dismutase/metabolismoRESUMO
Data on Helicobacter pylori (H. pylori) infection and virulence factors in countries across West Africa are scattered. This systematic review seeks to present an update on the status of H. pylori infection focusing on prevalence rate, distribution of virulent genes, and their link to clinical outcomes across countries in the western part of Africa. This information is expected to broaden the knowledge base of clinicians and researchers regarding H. pylori infection and associated virulence factors in West African countries. Search Method. A comprehensive search of the scientific literature in PubMed and ScienceDirect was conducted using the search terms including "Helicobacter pylori infection in West Africa". Databases were sourced from January 1988 to December 2018. Results. Data on the incidence of H. pylori infection and related pathological factors were found for some countries, whereas others had no information on it. Smoking, alcohol, exposure to high levels of carcinogens and diet were reported to be involved in the pathogenesis of gastroduodenal diseases and gastric cancer. Besides the environmental factors and genetic characteristics, there are important characteristics of H. pylori such as the ability to infect, replicate, and persist in a host that have been associated with the pathogenesis of various gastroduodenal diseases. Concluding Remarks. This systematic search has provided information so far available on H. pylori virulence factors and clinical outcomes in West Africa. Accordingly, this piece has identified gaps in the body of knowledge highlighting the need for more studies to clarify the role of H. pylori virulence factors and associated clinical outcomes in the burden of this bacterial infection in West Africa, as data from these countries do not give the needed direct relation.
Assuntos
Genes Bacterianos , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Helicobacter pylori/patogenicidade , África Ocidental , Infecções por Helicobacter/epidemiologia , Humanos , Prevalência , Resultado do Tratamento , Virulência/genéticaRESUMO
BACKGROUND: Cancer incidence and its related mortality is rising and is currently the second leading cause of death globally. In Africa, breast and prostate cancer in females and males, respectively, are the worst globally. However, biomarkers for their early detection and prognosis are not well developed. This study sought to investigate circulating cell-free DNA (ccfDNA) integrity and its potential utility as diagnostic and/or prognostic biomarker. Circulating cell-free DNA (ccfDNA) is degraded DNA fragments released into the blood plasma. In healthy individuals, the source of ccfDNA is solely apoptosis, producing evenly sized shorter DNA fragments. In cancer patients, however, necrosis produces uneven longer cell-free DNA fragments in addition to the shorter fragments originating from apoptosis. DNA integrity, expressed as the ratio of longer fragments to total DNA, may be clinically useful for the detection of breast and prostate cancer progression. METHODS: Sixty-four (64) females, consisting of 32 breast cancer patients and 32 controls, and 61 males (31 prostate cancer patients and 30 controls) were included in the study. Each participant donated 5â¯ml peripheral blood from which sera were separated. Real-time qPCR was performed on the sera to quantify ALU 115 and 247 levels, and DNA integrity (ALU247/ALU115) determined. RESULTS & CONCLUSION: ALU species 115 and 247 levels in serum were elevated in breast and prostate cancer patients compared to their counterpart healthy controls. DNA integrity was higher in prostate cancer patients than in the control, but in breast cancer patients was lower compared to their controls. In prostate but not in breast cancers, DNA integrity increased with disease severity and higher staging.
Assuntos
Neoplasias da Mama/sangue , Ácidos Nucleicos Livres/sangue , DNA de Neoplasias/sangue , Detecção Precoce de Câncer/métodos , Neoplasias da Próstata/sangue , Adulto , Idoso , Elementos Alu/genética , Biomarcadores Tumorais/sangue , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Ácidos Nucleicos Livres/genética , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Glutathione S-transferase (GST) family of enzymes are involved in a two-stage detoxification process of a wide range of environmental toxins, carcinogens and xenobiotics. The GST enzymes play important roles in oxidative stress pathways, and polymorphisms in the GSTM1 and GSTT1 genes mediate susceptibility and outcome in different diseases. Human immunodeficiency virus (HIV) infection is associated with oxidative stress, but there is limited data on the frequency of deleted GSTM1 and GSTT1 genes in HIV/AIDS patients and their effect on progression among Ghanaians. This study sought to investigate the association between homozygous deletion of GSTM1 and GSTT1 genes (both null deletion) with HIV/AIDS disease progression in Ghanaian patients. HIV-infected individuals on antiretroviral therapy (ART), ART-naïve HIV patients, and HIV seronegative individuals were recruited for the study. HIV/AIDS disease progression was assessed by measuring CD4+ cell count and viral load of the patients, and GST polymorphism was determined by amplifying the GSTT1 and GSTM1 genes using multiplex PCR, with CYP1A1 gene as an internal control. The mean CD4+ count of patients that were naïve to ART (298 ± 243 cells/mm3) was significantly lower than that of patients on ART (604 ± 294 cells/mm3), and viral load was significantly lower in the ART-experienced group (30379 ± 15073 copies/mm3) compared to the ART-naïve group (209882 ± 75045 copies/mm3). Frequencies of GSTM1 and GSTT1 deletions were shown to be 21.9% and 19.8%, respectively, in the HIV patients, and patients with homozygous deletion of both GSTM1 and GSTT1 were more likely to have their CD4+ count rising above 350 cells/mm3 (OR = 6.44, 95% CI = 0.81-51.49, p = 0.039) suggesting that patients with homozygous deletion of GSTM1 and GSTT1 genes have slower disease progression. The findings of this study show that double deletion of glutathione S-transferases M1 and T1 is statistically associated with normal CD4+ count in patients diagnosed with HIV/AIDS. Further study is required to investigate the clinical importance of the both null deletion in HIV patients.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Glutationa Transferase/genética , Infecções por HIV/imunologia , HIV/imunologia , Homozigoto , Deleção de Sequência , Adulto , Estudos Transversais , Progressão da Doença , Feminino , Predisposição Genética para Doença , Genótipo , Infecções por HIV/genética , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de RiscoRESUMO
INTRODUCTION: There is limited data on the prevalence of thyroid dysfunction in Ghanaian individuals with chronic kidney disease (CKD). Studies exploring the effect of thyroid hormones on renal function decline are also scanty. Unrecognized thyroid dysfunction in CKD may increase the burden of adverse health outcomes. The aim of this study was to determine thyroid hormone status and lipid profiles in patients with CKD attending the Renal Unit of the Korle-Bu Teaching Hospital. METHODS: 60 clinically euthyroid patients with CKD, and 65 clinically euthyroid subjects without CKD were recruited for this study. Estimation of effective glomerular filtration rate (eGFR) was done using the 4-variable Modification of Diet in Renal Disease (MDRD) formula with subsequent staging of CKD (stages 2-4). Collected venous blood samples from all study participants were analyzed for creatinine, free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), total cholesterol (TC), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) and triglycerides (TG). RESULTS: Levels of TC, HDL, LDL, and TSH levels did not differ significantly between the two study groups. However, TG, VLDL, FT3 and FT4 levels were significantly higher in CKD patients than in the control group. TC, TG, HDL, LDL, VLDL and TSH levels were not significantly different between stages of CKD in study subjects, although FT4 and FT3 levels were significantly different between all stages of CKD. CONCLUSION: Higher levels of FT3 and FT4 but not TSH, are associated with the incidence of CKD and eGFR decline in Ghanaian CKD patients.
Assuntos
Lipídeos/sangue , Insuficiência Renal Crônica/sangue , Doenças da Glândula Tireoide/diagnóstico , Hormônios Tireóideos/sangue , Adulto , Idoso , Estudos de Casos e Controles , Creatinina/sangue , Feminino , Gana/epidemiologia , Taxa de Filtração Glomerular , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/fisiopatologia , Doenças da Glândula Tireoide/epidemiologia , Testes de Função Tireóidea , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
BACKGROUND: Breast cancer, the most commonly diagnosed cancer among women and leading cause of cancer-related deaths worldwide, exhibits aggressive behavior in indigenous African women evidenced by high histologic grade tumours with low hormone receptor positivity. Aggressive breast cancers grow quickly, easily metastasize and recur and often have unfavourable outcomes. The current study investigated candidate genes that may regulate tumour aggression in Ghanaian women. We hypothesize that increased expression and function of certain genes other than the widely-held view attributing breast cancer aggression in African populations to their younger population age may be responsible for the aggressive nature of tumours. METHODS: Employing ELISA, we assayed for vimentin and death-associated protein kinase 1 (DAPK1) from thawed archived (stored at -80 °C) serum samples obtained from 40 clinically confirmed Ghanaian breast cancer patients and 40 apparently healthy controls. Patients' clinical records and tumour parameters matching the samples were retrieved from the database of the hospital. ANOVA was used to compare means of serum protein concentration among groups while Chi-square analysis was used for the categorical data sets with p-value ≤0.05 considered significant. Multiple logistic regression analysis was conducted to determine the association between protein concentration and tumour parameters. RESULTS: Of the 80 samples, 27 (33.8%) and 53 (66.2%) were from young (<35 years) and old (≥35 years), respectively. Vimentin and DAPK1 concentration were higher in patients than controls with higher levels in "young" age group than "old" age group. Vimentin concentration was highest in grade 3 tumours followed by grade 2 and 1 but that for DAPK1 was not significant. For vimentin, tumour area strongly correlated with tumour grade (r = 0.696, p < 0.05) but weakly correlated with tumour stage (r = 0.420, p < 0.05). Patient's age correlated with DAPK1 concentration (r = 0.393, p < 0.05). DAPK1 serum levels weakly correlated with cancer duration (r = 0.098, p = 0.27) and tumour size (r = 0.40, p < 0.05). CONCLUSION: Serum concentration of Vimentin and DAPK1 are elevated in Ghanaian breast cancer patients. This may be partly responsible for aggressive nature of the disease among the population. Vimentin and DAPK1 should be explored further as potential breast cancer biomarkers in Africans.
RESUMO
AIM: Smoking has been established as a major risk factor for cardiovascular disease. It causes oxidative stress and sub-clinical inflammation, which undermine the antioxidant defense system of the body. We reasoned that natural antioxidant defense systems may be compromised in smokers. To this end, we examined whether haptoglobin (Hp), a potent antioxidant, is impacted negatively by smoking. METHODS: Study participants consisted of 121 current smokers and 105 healthy non-smokers without diabetes and without blood smear-positive P. falciparum. Smokers were defined as individuals who smoke at least 1 cigarette a week and are current smokers (occasional and regular). Baseline demographics, hematological indices, lipid profiles, blood pressure, lactate dehydrogenase activity and haptoglobin phenotypes were determined. RESULTS: Ahaptoglobinemia was found to be highly overrepresented in smokers (odds ratio (OR)=3.1, 95% confidence interval (CI)=1.5-6.5, p=0.002). This observation was not attributed to intravascular hemolysis. Hp2-2 phenotype was found to be under represented in smokers (OR=0.53, 95% CI=0.28-0.99, p=0.05). Smoking was confirmed to augment hypertension (diastolic blood pressure (DBP) and systolic blood pressure (SBP) in male smokers (p=0.0001). Interestingly, however, this appeared not to be related to lipid metabolism, as HDL was elevated (p=0.0007) while LDL was decreased (p=0.004) in smokers within the study population. CONCLUSION: We conclude that smoking is a risk factor for ahaptoglobinemia, which will impact negatively on anti-oxidant defenses and augment pro-oxidative stress effects.