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The clinical manifestation of foetal anaemia caused by maternal Kell alloantibodies differs from that caused by non-Kell alloantibodies. Severe anaemia develops in the foetus in the early weeks of gestation; therefore, proper management and early intervention are important. A systematic review and meta-analysis was performed to determine whether the anti-K1 titre can determine the sequelae of Kell alloimmunised pregnancies. Prospective and retrospective cohort studies were used to conduct a systematic review following a comprehensive literature search, in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Studies were screened based on a defined set of inclusion and exclusion criteria. A total of 5143 potential articles were identified. Ten studies were used in the meta-analysis of pregnancy outcomes for a specific anti-K1 titre cut-off. The meta-analysis identified statistical significance for intrauterine transfusion (ARD: 0.351; 95 % CI: 0.593-0.109; p-value = 0.004), hydrops (ARD: 0.808; 95 % CI: 1.145-0.472; p-value <0.001), intrauterine foetal death (ARD: 0.938; 95 % CI:1.344 to -0.533; p-value <0.001) and intrauterine transfusion for Doppler middle cerebral artery >1.5 MoM (ARD: 0.381; 95 % CI:1.079 to -0.317; p-value = 0.285). It was concluded that there is no correlation between anti-K1 titre and Kell sensitised pregnancy outcomes, but monitoring the anti-K1 titre is important to manage the pregnancy and it helps clinicians determine the need for intrauterine transfusions. Doppler middle cerebral artery peak systolic velocity is strongly correlated with foetal anaemia and is an efficient routine method for determining the need for intrauterine transfusions in pregnancies affected by anti-K1.
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BACKGROUND: Foetal anaemia is caused by a severe pregnancy complication, haemolytic disease of the foetus and newborn. Intrauterine transfusions (IUTs) are performed to treat foetal anaemia in alloimmunised pregnant women. If left untreated hydrops can develop thereby reducing the chance of survival. Survival rates have improved but the procedure is not without complications. Procedure-related complications can be associated with early gestational age, hence delaying IUT could improve outcomes. This review aims to determine the effectiveness and safety of IUTs by examining survival and mortality rates, procedure-related complications with associated foetal mortality and the influence of hydrops. STUDY DESIGN AND METHOD: A systematic review was conducted by searching keywords in four scientific databases from January 2000 to April 2022. A meta-analysis was performed with the OpenMeta-Analyst software using an arcsine transformed proportion with the binary random-effects model and maximum likelihood method. RESULTS: Fifteen studies were identified as eligible and used in the meta-analysis. The forest plots all showed statistically significant outcomes with heterogeneity of data. Results indicated a greater foetal survival rate with IUT to treat anaemic foetuses, a low foetal mortality rate, and low risk of procedure-related complications associated with foetal loss but a higher risk of foetal mortality when hydrops is present. CONCLUSION: The findings of this systematic review and meta-analysis provide evidence that IUT is a safe and effective treatment for foetal anaemia in the absence of hydrops when experienced personnel perform the procedure to minimise the risk of procedure-related complications.
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Autoimmune haemolytic anaemia (AIHA) is a rare clinical condition with immunoglobulin fixation on the surface of erythrocytes, with or without complement activation. The pathophysiology of AIHA is complex and multifactorial, presenting functional abnormalities of T and B lymphocytes that generate an imbalance between lymphocyte activation, immunotolerance and cytokine production that culminates in autoimmune haemolysis. In AIHA, further laboratory data are needed to predict relapse and refractoriness of therapy, and thus, prevent adverse side-effects and treatment-induced toxicity. The metabolomic profile of AIHA has not yet been described. Our group developed a cross-sectional study with follow-up to assess the metabolomic profile in these patients, as well as to compare the metabolites found depending on the activity and intensity of haemolysis. We analysed the plasma of 26 patients with primary warm AIHA compared to 150 healthy individuals by mass spectrometry. Of the 95 metabolites found in the patients with AIHA, four acylcarnitines, two phosphatidylcholines (PC), asymmetric dimethylarginine (ADMA) and three sphingomyelins were significantly increased. There was an increase in PC, spermine and spermidine in the AIHA group with haemolytic activity. The PC ae 34:3/PC ae 40:2 ratio, seen only in the 12-month relapse group, was a predictor of relapse with 81% specificity and 100% sensitivity. Increased sphingomyelin, ADMA, PC and polyamines in patients with warm AIHA can interfere in autoantigen and autoimmune recognition mechanisms in a number of ways (deficient action of regulatory T lymphocytes on erythrocyte recognition as self, negative regulation of macrophage nuclear factor kappa beta activity, perpetuation of effector T lymphocyte and antibody production against erythrocyte antigens). The presence of PC ae 34:3/PC ae 40:2 ratio as a relapse predictor can help in identifying cases that require more frequent follow-up or early second-line therapies.
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Anemia Hemolítica Autoimune , Humanos , Anemia Hemolítica Autoimune/terapia , Hemólise , Estudos Transversais , EritrócitosRESUMO
Lactococcus spp. are industrially crucial lactic acid bacteria (LAB) used to manufacture lactic acid, pickled vegetables, buttermilk, cheese, and many kinds of delicious dairy foods and drinks. In addition to these, they are also being used as probiotics in specific formulations. However, their uses as probiotics are comparatively less than the other LAB genera. The present communication hypothesizes to validate the probiotic potentiality of two new Lactococcus lactis subsp. lactis strains for their future uses. These native food fermenting strains were characterized for in vitro acid tolerance, tolerance to simulated gastric and pancreatic juices, autoaggregation and co-aggregation, hydrophobicity, haemolytic activity, bile salt deconjugation, cholesterol removal, antimicrobial spectrum, and antibiotic sensitivity. The in vivo live bacterial feeding of these strains for 30 days was done in Swiss albino mice either singly or in combination with prebiotic inulin and evaluated for hypocholesterolemic activity, immune enhancement, and gut colonization efficiency and compared with the commercial probiotic consortia. The study revealed that the strains could survive in human gut bile concentration, gastric pH conditions at pH 2.0, 3.0, and 8.0 for 6 h, had a broad antibacterial spectrum, and cholesterol binding efficacy. The strains could survive with higher colony-forming units (CFU/mL) when amended with sodium caseinate. The strains had autoaggregation ranges from 15 to 25% over 24 h and had a significant co-aggregation with both lactic acid and Gram-positive and Gram-negative bacterial strains related to human illness. The strains also showed solvent and media-specific hydrophobicity against n-hexane and xylene. The live bacterial feeding either singly or in combination with prebiotic inulin resulted in a significant reduction of LDL (low-density lipoprotein), VLDL (very low-density lipoprotein) cholesterol and triglyceride (TG), and a significant increase in HDL (high-density lipoprotein) cholesterol level, and improved gut colonization and gut immunomodulation. The results prove that these non-haemolytic, non-toxic strains had significant health benefits than the commercial probiotics consortium with the recommended prebiotics mix. Thus, these new Lactococcus lactis subsp. lactis strains could be trialled as a new probiotic combination for human and animal feeds.
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Lactobacillales , Lactococcus lactis , Probióticos , Simbióticos , Animais , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Bactérias , Inulina , Ácido Láctico/metabolismo , Lactococcus lactis/metabolismo , Lipoproteínas LDL , CamundongosRESUMO
Antimicrobial peptides (AMPs) represent a promising and effective alternative for combating pathogens, having some advantages compared to conventional antibiotics. However, AMPs must also contend with complex and specialised Gram-negative bacteria envelops. The variety of lipopolysaccharide and phospholipid composition in Gram-negative bacteria strains and species are decisive characteristics regarding their susceptibility or resistance to AMPs. Such biological and structural barriers have created delays in tuning AMPs to deal with Gram-negative bacteria. This becomes even more acute because little is known about the interaction AMP-Gram-negative bacteria and/or AMPs' physicochemical characteristics, which could lead to obtaining selective molecules against Gram-negative bacteria. As a consequence, available AMPs usually have highly associated haemolytic and/or cytotoxic activity. Only one AMP has so far been FDA approved and another two are currently in clinical trials against Gram-negative bacteria. Such a pessimistic panorama suggests that efforts should be concentrated on the search for new molecules, designs and strategies for combating infection caused by this type of microorganism. This review has therefore been aimed at describing the currently available AMPs for combating Gram-negative bacteria, exploring the characteristics of these bacteria's cell envelop hampering the development of new AMPs, and offers a perspective regarding the challenges for designing new AMPs against Gram-negative bacteria.
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Introduction: Introduction: Thrombotic microangiopathies (TMAs) are rare disorders associated with fatal outcomes if left uncared for. However, healthcare problems in developing countries tend to limit medical assistance to patients. Methods: Methods: We prospectively studied an Argentine cohort of 294 consecutive patients from 2013 to 2016. Patients' subcategory classification relied on clinical symptoms and presence or absence of trigger events associated with TMA. Results: Main suspected disorders were the primary TMAs known as thrombotic thrombocytopenic purpura (TTP) (n = 72/294, 24%) and atypical haemolytic uraemic syndrome (aHUS) (n = 94/294, 32%). In acute phase, demographic parameters for acquired TTP (aTTP) (n = 28) and aHUS (n = 47) showed that both groups were characterised by a young median age (37 and 25 years, respectively) and female predominance (60% and 86%). Median of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 activity was significantly lower in aTTP than in aHUS group (1.4% vs 83%) and was associated with a more severe thrombocytopenia (15 × 109 vs 53 × 109/L). Creatinine (Cr) and urea (Ur) were significantly increased in aHUS compared to aTTP subjects (Cr: 3.7 vs 0.7 mg/dL, Ur: 118 vs 33 mg/dL). Gastrointestinal and neurological symptoms were more frequent in aHUS and aTTP, respectively. Conclusion: The first description of a TMA cohort in Argentina revealed similar clinical presentations to those of other countries.
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RESUMEN La crisis renal esclerodérmica (CRS) es una manifestación rara de la esclerosis sistémica (ES). Se presenta como hipertensión arterial de nuevo inicio, empeoramiento o aceleración de la hipertensión arterial crónica o rápido deterioro de la función renal, frecuentemente acompañada de signos de hemolisis microangiopática. Su relación con el síndrome hemo lítico urémico es infrecuente, existiendo tan solo un caso similar reportado en la literatura. Presentamos el caso de una mujer de 36 arios en tratamiento para ES con cefalea global, pulsátil e intensa, convulsión tónico-clónica, cifras de presión arterial altas, falla renal aguda y hemólisis no autoinmune persistente. La evaluación de ADAMTS13 mostró un 60,6% de actividad. El estudio genético para búsqueda de mutaciones predisponentes para sín drome hemolítico urémico atípico (SHUa) reveló variante homocigota en el gen ADAMTS13, c.3287G>A (p.Arg1096His). Se inició tratamiento con eculizumab, observándose en poco tiempo mejoría de la hemólisis, función renal y estado clínico, con algunos efectos benéficos notorios e inesperados sobre la ES.
ABSTRACT Scleroderma renal crisis (SRC) is a rare manifestation of systemic sclerosis (SSc), presented as hypertension of new onset, worsening and / or acceleration of chronic hypertension, or rapid deterioration of renal function, often accompanied by signs of microangiopathic haemolysis. It is rarely associated with haemolytic uraemic syndrome, and there is only one similar case reported in the literature. The case is presented here of a 36-year-old woman on treatment for SSc with global, pulsatile and intense headache, clonic tonic convulsions, high blood pressure levels, acute renal failure, and persistent non-autoimmune haemoly sis. The evaluation of ADAMTS13 showed 60.6% of activity. The genetic study to search for mutations predisposing to atypical haemolytic uraemic syndrome (aHUS) revealed a homozygous variant in ADAMTS13 gene, c.3287G>A (p.Arg1096His). Eculizumab was star ted, with an improvement being observed in a short time in the haemolysis, renal function, and clinical status, with some notable and unexpected beneficial effects on SSc.
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Humanos , Feminino , Adulto , Terapêutica , Síndrome Hemolítico-Urêmica , Rim , Escleroderma Sistêmico , Sinais e Sintomas , Anticorpos MonoclonaisRESUMO
The aim of this study was to synthesize and investigate the in vitro antifungal properties of 23 cinnamyl Schiff bases. In addition, cytotoxic effects of such cinnamyl Schiff bases against human lung, kidney or red blood cells were also checked. The compounds were synthesized in a single-step, 2 min of reaction under microwave irradiation produced up to 97% yield. Six of the 23 cinnamyl Schiff bases possessed antifungal activities against strains of Candida, Aspergillus, Fonsecaea and, particularly, Cryptococcus species. Indeed, cinnamyl Schiff bases 1 and 23 exhibited minimum inhibitory concentration (MIC) values more than twofold lower than fluconazole (FCZ) against all the Cryptococcus neoformans strains (MIC = 1·33, 1·4 and 5·2 µg ml-1 , respectively) and Cryptococcus gattii strains (MIC = 5·3, 2·8 and 9·2 µg ml-1 , respectively) (12 strains of each species) while cinnamyl Schiff base 11 was as potent as FCZ against all strains from both Cryptococcus species. No significant cytotoxic effects were observed for Schiff bases against human lung, kidney or red blood cells, all presenting selective indexes higher than 10. In conclusion, this study revealed cinnamyl Schiff bases, especially 1 and 23, as new lead anticryptococcal agents for the discovery of novel antifungal drugs. SIGNIFICANCE AND IMPACT OF THE STUDY: The occurrence and severity of fungal infections have increased in recent decades due to resistance to available antifungal drugs and the appearance of new emerging pathogens. Thus, the search for new antifungal agents is mandatory. From a series of 23 cinnamyl Schiff bases, two compounds (1 and 23) were interrogated as new anticryptococcal agents without significant cytotoxicity against human lung, kidney or red blood cells. In turns, these new Schiff bases are lead compounds for the discovery of novel antifungal drugs.
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Antifúngicos/farmacologia , Micoses/tratamento farmacológico , Bases de Schiff/farmacologia , Antifúngicos/síntese química , Antineoplásicos/farmacologia , Aspergillus/efeitos dos fármacos , Candida/efeitos dos fármacos , Cryptococcus gattii/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Fluconazol/farmacologia , Fonsecaea/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Bases de Schiff/síntese químicaRESUMO
Antimicrobial peptides (AMPs) have been recognised as a significant therapeutic option for mitigating resistant microbial infections. It has been found recently that Plasmodium falciparum-derived, 20 residue long, peptide 35409 had antibacterial and haemolytic activity, making it an AMP having reduced selectivity, and suggesting that it should be studied more extensively for obtaining new AMPs having activity solely targeting the bacterial membrane. Peptide 35409 was thus used as template for producing short synthetic peptides (<20 residues long) and evaluating their biological activity and relevant physicochemical characteristics for therapeutic use. Four of the sixteen short peptides evaluated here had activity against E. coli without any associated haemolytic effects. The 35409-1 derivative (17 residues long) had the best therapeutic characteristics as it had high selectivity for bacterial cells, stability in the presence of human sera, activity against E. coli multiresistant clinical isolates and was shorter than the original sequence. It had a powerful membranolytic effect and low potential for inducing resistance in bacteria. This peptide's characteristics highlighted its potential as an alternative for combating infection caused by E. coli multiresistant bacteria and/or for designing new AMPs.
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The objectives of this study were to examine the physicochemical and structural properties of peptide derivatives of dermaseptin S4, investigate their detrimental effects on red blood and sperm cells and ascertain their antibacterial potency to control bacterial contaminants in fresh bovine semen. The dermaseptin S4 peptide derivatives used in this study were K4S4, S4(5-28), S4(5-28)a, K20S4(5-28), K4S4(1-16)a, K4S4(1-15)a and K4S4(1-15). Peptides K4S4, S4(5-28)a, K20S4(5-28), K4S4(1-15)a and K4S4(1-16)a, with a higher positive charge, were the most potent against the bacterial strains tested, with the lowest minimum inhibitory concentration (MIC), whereas S4(5-28) and K4S4(1-15), with a lower positive charge, showed the highest MIC (p < .01). Haemolysis percentage depended on peptide concentration (p < .01). The K4S4 was the most powerful haemolytic peptide, showing the highest haemolysis percentage at all peptide concentrations (p < .01). In contrast, S4(5-28), S4(5-28)a, K20S4(5-28) and K4S4(1-15) were not able to produce 50% cell lysis up to 100 µM (p < .01). All peptides reduced sperm motility in a dose-dependent manner when used in concentrations from 16 to 64 µM (p < .01). The highest reduction was seen due to K4S4 activity, and the lowest reductions of sperm motility were observed due to K4S4(1-16)a and K4S4(1-15)a activity (p < .01). Hence, we can conclude that K4S4(1-16)a and K4S4(1-15)a at a concentration of approximately 15 µM are the most promising peptides as antibacterial agents in fresh bovine semen, because at this concentration, they showed the most potent antibacterial activity against evaluated strains without significant effects on haemolysis or a reduction in sperm motility.