Obtenção de sistemas multiparticulados de isoniazida revestidos com polímero de liberação entérica

Known for thousands of years, tuberculosis (TB) is the leading cause of mortality by a single infectious disease due to lack of patient adherence to available treatment regimens, the rising of multidrug resistant strains of TB (MDR-TB) and co-infection with HIV virus. Isoniazid and rifampicin are the most powerful bactericidal agents against M. tuberculosis. Because of that, this couple of drugs becomes unanimity in anti-TB treatment around the world. However, the rifampicin in acidic conditions in the stomach can be degraded rapidly, especially in the presence of isoniazid, which reduces the amount of available drug for absorption, as well as its bioavailability, contributing to the growing resistance to tuberculostatic drugs. Rifampicin is well absorbed in the stomach because of its high solubility between pH 1 and 2 and the gastric absorption of isoniazid is considered poor, therefore it is mostly intestinal. This work has as objective the development of gastro-resistant multiple-systems (granules and pellets) of isoniazid aiming to prevent the contact with rifampicin, with consequent degradation in acid stomach and modulate the release of isoniazid in the intestine. Granules of isoniazid were obtained by wet method using both alcoholic and aqueous solutions of PVP K-30 as aggregating and binder agent, at proportions of 5, 8 and 10%. The influence of the excipients (starch, cellulose or filler default) on the physical and technological properties of the granules was investigated. The pellets were produced by extrusionesferonization technique using isoniazid and microcrystalline cellulose MC 101 (at the proportion of 85:15) and aqueous solution of 1% Methocel as platelet. The pellets presented advantages over granular, such as: higher apparent density, smaller difference between apparent and compaction densities, smoother surface and, especially, smaller friability, and then were coated with an organic solution of Acrycoat L 100 ® in a fluidized bed. Different percentages of coating (15, 25 and 50%) were applied to the pellets which had their behavior evaluated in vitro by dissolution in acidic and basic medium. Rifampicin dissolution in the presence of uncoated and coated isoniazid pellets was evaluated too. The results indicate that the gastro resistance was only achieved with the greatest amount of coating and isoniazid is released successfully in basic step. The amount of rifampicin in the dissolution medium when the isoniazid pellets were not coated was lower than in the presence of enteric release pellets. Therefore, the polymer Acrycoat L 100 ® was efficient for coating with gastro-resistant function and can solve the problem of low bioavailability of rifampicin and help to reduce its dosage

Síndrome de Guillain-Barré: epidemiologia, prognóstico e fatores de risco

Introduction. Guillain-Barré syndrome (GBS) is an immune-mediated polyneuropathy and the principal cause of acute neuromuscular paralysis. The most prominent GBS subtypes are: acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor-sensory axonal neuropathy (AMSAN) and Fisher syndrome (FS). Differences in geographical distribution of variants have been reported. In Brazil, there are few studies describing the characteristics of GBS, but none on the frequency of GBS variants and their clinical manifestations. Infection-induced aberrant immune response resulting from molecular mimicry and formation of cross-reacting antibodies, contribute to complement activation. Functional biallelic polymorphism in immunoglobulin receptors that influence the affinity of IgG subclasses and the type of immune response have been described, suggesting genetic susceptibility to developing disease. It remains unclear whether individuals carrying different FCGR alleles have differential risk for GBS and⁄or disease severity. The goals of this study were: (1) To characterize GBS and describe the clinical findings in a cohort of patients with GBS from the state of Rio Grande do Norte, Brazil; (2) to determine whether polymorphism in FCGR were associated with development of GBS, and (3) to tease out whether the global gene expression studies could be a tool to identify pathways and transcriptional networks which could be regulated and decrease the time of disease. Methods. Clinical and laboratory data for 149 cases of GBS diagnosed from 1994 to 2013 were analyzed. Genomic DNA and total RNA were extracted from whole blood. Antigangliosides antibodies were determined in the sera. In addition, we also assessed whether FCGR polymorphism are present in GBS (n=141) and blood donors (n=364), and global gene expressions were determined for 12 participants with GBS. Blood samples were collected at the diagnosis and post-recovery. Results. AIDP was the most frequent variant (81.8%) of GBS, followed by AMAN (14.7%) and AMSAN (3.3%). The incidence of GBS was 0.3 ⁄ 100,000 people for the state of Rio Grande do Norte and cases occurred at a younger age. GBS was preceded by infections, with the axonal variant associated with episodes of diarrhea (P = 0.025). Proximal weakness was more frequent in AIDP, and distal weakness predominant in the axonal variant. Compared to 42.4% of cases with AIDP (P<0.0001), 84.6% of cases with the axonal variant had nadir in <10 days. Individuals with the axonal variant took longer to recover deambulation (P<0.0001). The mortality of GBS was 5.3%. A worse outcome was related to an axonal variant (OR17.063; P=0.03) and time required to improve one point in the Hughes functional scale (OR 1.028; P=0.03). The FCGR genotypes and allele frequencies did not differ significantly between the patients with GBS and the controls (FCGR2A p=0.367 and FCGR3A p=0.2430). Global gene expression using RNAseq showed variation in transcript coding for protein isoforms during acute phase of disease. Conclusions. The annual incidence of GBS was 0.3 per 100,00 and there was no seasonal pattern. A predominance of the AIDP variant was seen, and the incidence of the disease decreased with age. The distribution of weakness is a function of the clinical variants, and individuals with the axonal variant had a poorer prognosis. Early diagnosis and variant identification leads to proper intervention decreasing in long-term morbidity. FCGR polymorphisms do not seem to influence susceptibility to GBS in this population. This study found deregulated genes and signs of transcriptional network alterations during the acute and recovery phases in GBS. Identification of pathways altered during disease might be target for immune regulation and with potential to ameliorate symptoms.