Controlled release and antiviral activity of acyclovir-loaded PLA/PEG nanofibers produced by solution blow spinning.

Herpetic dermatitis and oral recurrent herpes (ORH) are among the most common human infections. Antiviral drugs such as acyclovir (ACV) are used in the standard treatment for ORH. Despite its therapeutic efficacy, ACV is continuously and repetitively administered in high doses. In this sense, the development of controlled release drug delivery systems such as core-shell fibers have a great potential in the treatment of ORH. In this work, poly(lactic acid)/poly(ethylene glycol) (PLA/PEG) fibers were produced by solution blow spinning (SBS) for the controlled release of ACV encapsulated in the core. PLA/PEG nanofibers containing four different blend ratios (100:0, 90:10, 80:20 and 70:30 wt%) without or with 10 wt% ACV were characterized by scanning electron microscopy (SEM), thermogravimetry (TG) and differential scanning calorimetry (DSC). The ACV release profile for 21 days was accessed by UV-Vis spectroscopy. Static water contact angles of the spun fiber mats were measured by the sessile drop method to evaluate fiber wettability upon contact with skin for transdermal release. Cytotoxicity and antiviral efficacy against Herpes simplex viruses (HSV-1) were evaluated using Vero cells. ACV addition did not impact on morphology, but slightly improved thermal stability of the fibers. Addition of hydrophilic PEG in PLA/PEG blends, however, increased drug release as confirmed by contact angle measurements and release profile. The in vitro tests showed the effectiveness of the drug delivery systems developed in reducing HSV-1 viral titer, which is related to the judicious combination of polymers used in the fibrous mats, in addition to not being cytotoxic to Vero cells. These results show the great potential of PLA/PEG solution blow-spun fibers in the controlled release of ACV to develop practical devices for the treatment of cold sores, while favoring the aesthetic appearance by covering them with a soft tissue patch (fibrous mats).

Catechins as Model Bioactive Compounds for Biomedical Applications.

Research regarding polyphenols has gained prominence over the years because of their potential as pharmacological nutrients. Most polyphenols are flavanols, commonly known as catechins, which are present in high amounts in green tea. Catechins are promising candidates in the field of biomedicine. The health benefits of catechins, notably their antioxidant effects, are related to their chemical structure and the total number of hydroxyl groups. In addition, catechins possess strong activities against several pathogens, including bacteria, viruses, parasites, and fungi. One major limitation of these compounds is low bioavailability. Catechins are poorly absorbed by intestinal barriers. Some protective mechanisms may be required to maintain or even increase the stability and bioavailability of these molecules within living organisms. Moreover, novel delivery systems, such as scaffolds, fibers, sponges, and capsules, have been proposed. This review focuses on the unique structures and bioactive properties of catechins and their role in inflammatory responses as well as provides a perspective on their use in future human health applications.

Immunoglobulin Therapy in a Patient With Severe Chikungunya Fever and Vesiculobullous Lesions.

Chikungunya virus (CHIKV) is an emerging arbovirus whose transmission has already been reported in several countries. Although the majority of individuals acutely infected with CHIKV appear to become asymptomatic, reports showing the occurrence of atypical and severe forms of the disease are increasing. Among them, the neurological and skin manifestations require medical attention. Treatment of CHIKV infection is almost symptomatic. In this sense, we report the case of a 56-years-old man who presented fever, headaches, paresthesia and pain in the right arm with visible red spots on the skin starting 30 days before Hospital admission. Tests determined Chikungunya infection and excluded other co-morbidities. Disease evolved with edema in hands and feet and extensive hemorrhagic bullous lesions on the skin of upper and lower limbs. Variations in hematological counts associated with liver dysfunction determined this patient's admission to the Intensive Care Unit. Then, he received intravenous antibiotic and immunoglobulin therapy (400 mg/Kg/day for the period of 5 days) with total recovery from the lesions after 10 days of follow-up. A general improvement in blood cell count and successful wound healing was observed. After discharge, no other clinical sign of the disease was reported until nowadays. This case reports for the first time the successful administration of intravenous immunoglobulin therapy to a patient with severe atypical dermatological form of Chikungunya Fever without any associated comorbidity.

Plant Extracts Loaded in Nanostructured Drug Delivery Systems for Treating Parasitic and Antimicrobial Diseases.

BACKGROUND: Plant extracts loaded in nanostructured drug delivery systems (NDDSs) have been reported as an alternative to current therapies for treating parasitic and antimicrobial diseases. Among their advantages, plant extracts in NDSSs increase the stability of the drugs against environmental factors by promoting protection against oxygen, humidity, and light, among other factors; improve the solubility of hydrophobic compounds; enhance the low absorption of the active components of the extracts (i.e., biopharmaceutical classification II), which results in greater bioavailability; and control the release rate of the substances, which is fundamental to improving the therapeutic effectiveness. In this review, we present the most recent data on NDDSs using plant extracts and report results obtained from studies related to in vitro and in vivo biological activities.

Expression pattern of transcription factors and intracellular cytokines reveals that clinically cured tuberculosis is accompanied by an increase in Mycobacterium-specific Th1, Th2, and Th17 cells.

Tuberculosis (TB) remains a major global health problem and is the second biggest cause of death by infectious disease worldwide. Here, we investigate in vitro the Th1, Th2, Th17, and Treg cytokines and transcriptional factors produced after Mycobacterium-specific antigen stimulation in patients with active pulmonary tuberculosis, clinically cured pulmonary tuberculosis, and healthy donors with a positive tuberculin skin test (TST+). Together, our data indicate that clinical cure after treatment increases the percentages of Mycobacterium-specific Th1, Th2, and Th17 cells compared with those found in active-TB and TST+ healthy donors. These results show that the host-parasite equilibrium in latent TB breaks in favor of the microorganism and that the subsequent clinical recovery posttreatment does not return the percentage levels of such cells to those observed in latent tuberculosis. Additionally, our results indicate that rather than showing an increase in the percentage of Mycobacterium-specific Tregs, active-TB patients display lower Th1 : Treg and Th17 : Treg ratios. These data, together with lower Th1 : Th2 and Th17 : Th2 ratios, may indicate a mechanism by which the breakdown of the host-parasite equilibrium leads to active-TB and changes in the repertoire of Mycobacterium-specific Th cells that are associated with clinical cure after treatment of pulmonary tuberculosis.

CD28 family and chronic rejection: "to belatacept...And beyond!".

Kidneys are one of the most frequently transplanted human organs. Immunosuppressive agents may prevent or reverse most acute rejection episodes; however, the graft may still succumb to chronic rejection. The immunological response involved in the chronic rejection process depends on both innate and adaptive immune response. T lymphocytes have a pivotal role in chronic rejection in adaptive immune response. Meanwhile, we aim to present a general overview on the state-of-the-art knowledge of the strategies used for manipulating the lymphocyte activation mechanisms involved in allografts, with emphasis on T-lymphocyte costimulatory and coinhibitory molecules of the B7-CD28 superfamily. A deeper understanding of the structure and function of these molecules improves both the knowledge of the immune system itself and their potential action as rejection inducers or tolerance promoters. In this context, the central role played by CD28 family, especially the relationship between CD28 and CTLA-4, becomes an interesting target for the development of immune-based therapies aiming to increase the survival rate of allografts and to decrease autoimmune phenomena. Good results obtained by the recent development of abatacept and belatacept with potential clinical use aroused better expectations concerning the outcome of transplanted patients.

Differential reactivity of serum immunoglobulins from Brazilian wild mammals to staphylococcal A and streptococcal G proteins.

Human pathogens have evolved to infect vertebrate hosts other than human beings without causing symptoms of the disease, thus permitting them to complete their life cycle and to develop into infectious forms. The identification and management of infected animals are alternatives to control dissemination of the disease and to prevent human illness. In the current study, the potential use of staphylococcal A or streptococcal G proteins was evaluated with enzyme-linked immunosorbent assays (ELISAs) for seroepidemiological studies. Sera were collected from animals that were representative of 23 different Brazilian wild mammals. A high protein A binding rate was observed in all animals, except for the orders Didelphimorphia, Artiodactyla, and Rodentia, in which affinity was medium or low. Affinity for streptococcal G protein was higher in animals of the order Artiodactyla, whereas no streptococcal G protein binding was observed in samples obtained from felines (order Carnivora). Bacterial protein binding to mammalian immunoglobulins was confirmed by immunoblotting. The results suggest that secondary detection systems should be better investigated in ELISA protocols before their implementation in seroepidemiological studies involving wild mammals.

Sepse neonatal precoce: níveis de citocinas no sangue de cordão umbilical no diagnóstico e durante o tratamento / Early-onset neonatal sepsis: cord blood cytokine levels at diagnosis and during treatment

OBJETIVO: Avaliar parâmetros clínicos, laboratoriais e citocinas séricas em 55 neonatos que desenvolveram sepse precoce. MÉTODOS: Avaliamos os parâmetros clínicos dos neonatos relacionados com sepse precoce. No dia do diagnóstico de sepse e 48 horas após, foram realizados o leucograma diferencial e a dosagem de proteína C reativa e glicemia. As citocinas IL-1β, IL-10, IL-6 e TNF-α foram determinadas no sangue do cordão, no dia do diagnóstico de sepse, 48 e 96 horas após o início do tratamento. RESULTADOS: O tempo de internação dos neonatos foi inversamente proporcional ao peso no nascimento. Os parâmetros clínicos foram variados, especialmente a temperatura corpórea. Alterações de glicemia foram frequentes, principalmente a hipoglicemia. A alteração de hemograma mais prevalente foi a leucopenia, devido principalmente à neutropenia. Os níveis de proteína C reativa se mostraram correlacionados com o índice neutrofílico. Observamos uma correlação positiva entre os níveis de TNF-α e IL-10 entre o curso da sepse precoce e os níveis observados no cordão umbilical. CONCLUSÕES: As alterações clínicas e laboratoriais entre os neonatos com sepse são variadas. Neonatos que apresentam elevações no padrão de citocinas no momento do parto permanecem com seus níveis elevados durante o processo infeccioso.

OBJECTIVE: To assess clinical and laboratory parameters and serum cytokine levels in 55 neonates who developed early-onset sepsis. METHODS: Clinical parameters associated with early-onset neonatal sepsis were assessed. White blood cell differential and serum C-reactive protein and glucose levels were measured upon diagnosis of sepsis and 48 hours later. IL-1β, IL-10, IL-6, and TNF-α levels were measured in cord blood samples obtained on the day of diagnosis and from samples collected 48 and 96 hours after treatment onset. RESULTS: Among newborns with early-onset sepsis, the length of hospital stay was inversely correlated with birth weight. Clinical parameters varied widely, especially body temperature. Blood glucose changes - particularly hypoglycemia - were common. Leukopenia, usually due to neutropenia, was the most prevalent change in blood cell count. C-reactive protein levels correlated with the immature-to-total neutrophil ratio. Serum TNF-α and IL-10 levels measured early in the course of sepsis were positively correlated with those detected in cord blood. CONCLUSIONS: Clinical and laboratory parameters varied widely among neonates with sepsis in this sample. In neonates who presented with increased cytokine levels at birth, this abnormality persisted throughout the infectious process.

Early-onset neonatal sepsis: cord blood cytokine levels at diagnosis and during treatment.

OBJECTIVE: To assess clinical and laboratory parameters and serum cytokine levels in 55 neonates who developed early-onset sepsis. METHODS: Clinical parameters associated with early-onset neonatal sepsis were assessed. White blood cell differential and serum C-reactive protein and glucose levels were measured upon diagnosis of sepsis and 48 hours later. IL-beta, IL-10, IL-6, and TNF-α levels were measured in cord blood samples obtained on the day of diagnosis and from samples collected 48 and 96 hours after treatment onset. RESULTS: Among newborns with early-onset sepsis, the length of hospital stay was inversely correlated with birth weight. Clinical parameters varied widely, especially body temperature. Blood glucose changes - particularly hypoglycemia - were common. Leukopenia, usually due to neutropenia, was the most prevalent change in blood cell count. C-reactive protein levels correlated with the immature-to-total neutrophil ratio. Serum TNF-α and IL-10 levels measured early in the course of sepsis were positively correlated with those detected in cord blood. CONCLUSIONS: Clinical and laboratory parameters varied widely among neonates with sepsis in this sample. In neonates who presented with increased cytokine levels at birth, this abnormality persisted throughout the infectious process.

Evaluation of a modified microscopic direct diagnosis of dermatophytosis.

Here we present a modified protocol for dematophyte diagnosis, utilizing a simple centrifugation step to significantly decrease false-negative results of the original KOH direct microscopy-based technique. Although culture constitutes the gold-standard diagnosis, the time spent for results is a limit. Fast and low-cost techniques are important for infection screening in underdeveloped countries.