Changes in Astroglial Water Flow in the Pre-amyloid Phase of the STZ Model of AD Dementia.

Alzheimer's disease (AD) is an age-dependent neurodegenerative disease that is typically sporadic and has a high social and economic cost. We utilized the intracerebroventricular administration of streptozotocin (STZ), an established preclinical model for sporadic AD, to investigate hippocampal astroglial changes during the first 4 weeks post-STZ, a period during which amyloid deposition has yet to occur. Astroglial proteins aquaporin 4 (AQP-4) and connexin-43 (Cx-43) were evaluated, as well as claudins, which are tight junction (TJ) proteins in brain barriers, to try to identify changes in the glymphatic system and brain barrier during the pre-amyloid phase. Glial commitment, glucose hypometabolism and cognitive impairment were characterized during this phase. Astroglial involvement was confirmed by an increase in glial fibrillary acidic protein (GFAP); concurrent proteolysis was also observed, possibly mediated by calpain. Levels of AQP-4 and Cx-43 were elevated in the fourth week post-STZ, possibly accelerating the clearance of extracellular proteins, since these proteins actively participate in the glymphatic system. Moreover, although we did not see a functional disruption of the blood-brain barrier (BBB) at this time, claudin 5 (present in the TJ of the BBB) and claudin 2 (present in the TJ of the blood-cerebrospinal fluid barrier) were reduced. Taken together, data support a role for astrocytes in STZ brain damage, and suggest that astroglial dysfunction accompanies or precedes neuronal damage in AD.

Calorie restriction protects against acute systemic LPS-induced inflammation.

Caloric restriction (CR) has been proposed as a nutritional strategy to combat chronic diseases, including neurodegenerative diseases, as well as to delay aging. However, despite the benefits of CR, questions remain about its underlying mechanisms and cellular and molecular targets.Objective: As inflammatory processes are the basis or accompany chronic diseases and aging, we investigated the protective role of CR in the event of an acute inflammatory stimulus.Methods: Peripheral inflammatory and metabolic parameters were evaluated in Wistar rats following CR and/or acute lipopolysaccharide (LPS) administration, as well as glial changes (microglia and astrocytes), in two regions of the brain (hippocampus and hypothalamus) involved in the inflammatory response. We used a protocol of 30% CR, for 4 or 8 weeks. Serum and brain parameters were analyzed by biochemical or immunological assays.Results: Benefits of CR were observed during the inflammatory challenge, where the partial reduction of serum interleukin-6, mediated by CR, attenuated the systemic response. In the central nervous system (CNS), specifically in the hippocampus, CR attenuated the response to the LPS, as evaluated by tumor necrosis factor alpha (TNFα) levels. Furthermore, in the hippocampus, CR increased the glutathione (GSH) levels, resulting in a better antioxidant response.Discussion: This study contributes to the understanding of the effects of CR, particularly in the CNS, and expands knowledge about glial cells, emphasizing their importance in neuroprotection strategies.

Management of patients with hypertension and chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. On behalf of the European Society of Hypertension Working Group on Hypertension and the Kidney.

Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70-95%]) than MRA (20% [10-30%]), SGLT2i (30% [20-50%]) or (GLP1-RA (10% [5-15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15-40%) vs 18% [10%-25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5-5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers' dosage reduction was the usual management.

What is the context? Hypertension is a strong independent risk factor for development of chronic kidney disease (CKD) and progression of CKD to ESKD. Improved adherence to the guidelines in the treatment of CKD is believed to provide further reduction of cardiorenal events. European Society of Hypertension Excellence Centres (ESH-ECs) have been developed in Europe to provide excellency regarding management of patients with hypertension and implement guidelines. Numerous deficits regarding general practitioner CKD screening, use of nephroprotective drugs and referral to nephrologists prior to referral to ESH-ECs have been reported. In contrast, real-life management of these patients among ESH-ECs is unknown. Before implementation of strategies to improve guideline adherence in Europe, we aimed to investigate how patients with CKD are managed among the ESH-ECs.What is the study about? In this study, a survey was conducted in 2023 by the ESH to assess management of CKD patients referred to ESH-ECs. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed among their centres.What are the results? RAAS blockers are initiated in 90% of ESH-ECs in CKD patients, but the initiation of MRA and SGLT2i is less frequently done. Hyperkalemia is the main barrier for initiation or adequate dosing of RAAS blockade, and its most reported management was RAAS blockers dosage reduction. These findings will be crucial to implement strategies in order to improve management of patients with CKD and guideline adherence among ESH-ECs.

[Whipple's Disease: retrospective analysis of twelve cases and review of the literature]. / Doença de Whipple: análisis retrospectivo de doce casos e revisión de la literature.

BACKGROUND: Whipple's disease is a rare and chronic bacterial disease with multiorganic involvement. Although there is no valid estimate of its actual prevalence, only about 1,000 cases have been reported. OBJECTIVE: To describe the demographic, clinical, laboratory, endoscopic and pathologic features, type of treatment used, its duration and response. METHODS: Based on the duodenal histology, we identified twelve cases of Whipple's disease in the Hospital Centre of Vila Nova de Gaia, between 1997 and 2010. RESULTS. Nine patients (75%) were male and the mean age at diagnosis was 58 years. All patients experienced at least one gastrointestinal and general symptom. Arthralgia were reported in four patients (33%) and occurred on average six years before the onset of gastrointestinal and general symptoms. In 10 patients the initial treatment was trimethoprim-sulfamethoxazole. The initial treatment duration was one year in 8 cases (80%). Seven patients (70%) had a symptomatic resolution between the third and sixth months of antibiotic therapy, as well as an endoscopic and histological improvement. Even in these patients, there was maintenance of periodic acid-Schiff positive macrophages, although in small number and with a more diffuse distribution. Gastrointestinal symptoms predominated in cases of clinical relapse. CONCLUSIONS: The gastrointestinal and general symptoms as well as the arthralgia were the predominant manifestations. The majority of patients showed clinical and endoscopic improvement in response to treatment with trimethoprim-sulfamethoxazole. However, in these cases periodic acid-Schiff positive macrophages can remain for years. Thus, in the absence of clinical deterioration, the presence of these structures is not indicative ofactive disease.

Screening and management of hypertensive patients with chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. A pilot survey based on questionnaire.

OBJECTIVE: Real-life management of hypertensive patients with chronic kidney disease (CKD) is unclear. METHODS: A survey was conducted in 2023 by the European Society of Hypertension (ESH) to assess management of CKD patients referred to ESH-Hypertension Excellence Centres (ESH-ECs) at first referral visit. The questionnaire contained 64 questions with which ESH-ECs representatives were asked to estimate preexisting CKD management quality. RESULTS: Overall, 88 ESH-ECs from 27 countries participated (fully completed surveys: 66/88 [75.0%]). ESH-ECs reported that 28% (median, interquartile range: 15-50%) had preexisting CKD, with 10% of them (5-30%) previously referred to a nephrologist, while 30% (15-40%) had resistant hypertension. The reported rate of previous recent (<6 months) estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) testing were 80% (50-95%) and 30% (15-50%), respectively. The reported use of renin-angiotensin system blockers was 80% (70-90%). When a nephrologist was part of the ESH-EC teams the reported rates SGLT2 inhibitors (27.5% [20-40%] vs. 15% [10-25], P  = 0.003), GLP1-RA (10% [10-20%] vs. 5% [5-10%], P  = 0.003) and mineralocorticoid receptor antagonists (20% [10-30%] vs. 15% [10-20%], P  = 0.05) use were greater as compared to ESH-ECs without nephrologist participation. The rate of reported resistant hypertension, recent eGFR and UACR results and management of CKD patients prior to referral varied widely across countries. CONCLUSIONS: Our estimation indicates deficits regarding CKD screening, use of nephroprotective drugs and referral to nephrologists before referral to ESH-ECs but results varied widely across countries. This information can be used to build specific programs to improve care in hypertensives with CKD.

[Symptomatic acute hepatitis C: the importance of diagnosis]. / Hepatite C aguda sintomática--a importância do diagnóstico.

Chronic infection by the hepatitis C virus (HCV) is one of the leading causes of chronic liver disease with an estimate worldwide prevalence of over 200 million people. Acute hepatitis C infection is usually asymptomatic and rarely identified in clinical practice, leading to chronic infection in about 80% of all cases. However, when symptomatic, only about 50% of acute infections progress to chronicity. Correctly identifying acute HCV infection is of paramount importance once it presents itself as an unique treatment opportunity with sustained virological response of about 90%, which is very distant from the 30% to 80% of sustained virological response achieved with standard chronic HCV treatment. The authors present four cases of acute HCV infection. There was spontaneous viral clearance in two pa- tients at week 12 of follow-up. In one case viral RNA was positive at week 12 but sustained virological response was eventually achieved after peginterferon alpha2a monotherapy.

Design and experimental validation of a new wheelchair seat stabilization system.

PURPOSE: Seat tilting wheelchair features can increase the comfort and safety of the user. Although many power wheelchairs have tilting mechanisms, they are often designed with a specific wheelchair model in mind. In this study, a design process for seat tilting mechanisms that can be applied to most rear-wheel drive wheelchair models is developed. METHODOLOGY: Equations were developed to describe the geometrical and load constraints that were used to size the electric actuator that powers the system and define its position. Finally, the equations were used to create the seat tilting mechanism of a prototype wheelchair, which was then tested. RESULTS: The equations yielded coherent results which showed that advantageous actuator positions from a load minimization perspective usually require dimensions that cannot be found in commercial actuators. Also, there are positions in which the load increases exponentially, which should be avoided. The tests showed that the system was able to function properly on the prototype wheelchair and that the actuator position affected the time taken for the actuator to execute different parts of the tilting movement. CONCLUSIONS: The design process presented here was successful and modelled by general equations that can be applied to most front-wheel drive wheelchairs. It presents a low-cost option for the design of seat tilting systems, which can increase their accessibility.

Developing new systems to provide improvements in assistive technologies is fundamental for social reintegration and quality of life improvement.Wheelchairs with a seat stabilization system for moving through inclined terrain can provide greater comfort and safety to the user.Adding low-cost functionalities to wheelchairs is essential to make them more accessible to people, therefore, this paper provides a design method of a new seat stabilization system applied to low-cost wheelchairs.

How S100B crosses brain barriers and why it is considered a peripheral marker of brain injury.

S100B is a 21-kDa protein that is produced and secreted by astrocytes and widely used as a marker of brain injury in clinical and experimental studies. The majority of these studies are based on measurements in blood serum, assuming an associated increase in cerebrospinal fluid and a rupture of the blood-brain barrier (BBB). Moreover, extracerebral sources of S100B are often underestimated. Herein, we will review these interpretations and discuss the routes by which S100B, produced by astrocytes, reaches the circulatory system. We discuss the concept of S100B as an alarmin and its dual activity as an inflammatory and neurotrophic molecule. Furthermore, we emphasize the lack of data supporting the idea that S100B acts as a marker of BBB rupture, and the need to include the glymphatic system in the interpretations of serum changes of S100B. The review is also dedicated to valorizing extracerebral sources of S100B, particularly adipocytes. Furthermore, S100B per se may have direct and indirect modulating roles in brain barriers: on the tight junctions that regulate paracellular transport; on the expression of its receptor, RAGE, which is involved in transcellular protein transport; and on aquaporin-4, a key protein in the glymphatic system that is responsible for the clearance of extracellular proteins from the central nervous system. We hope that the data on S100B, discussed here, will be useful and that it will translate into further health benefits in medical practice.

S100B Secretion in Astrocytes, Unlike C6 Glioma Cells, Is Downregulated by Lactate.

S100B is a calcium-binding protein produced and secreted by astrocytes in response to various extracellular stimuli. C6 glioma cells are a lineage commonly employed for astroglial studies due to the expression of astrocyte specific markers and behavior. However, in high-glucose medium, C6 S100B secretion increases, in contrast to the trend in primary astrocyte cultures. Additionally, S100B secretion decreases due to fluorocitrate (FC), a Krebs cycle inhibitor, highlighting a connection between S100B and metabolism. Herein, we investigate the impact of FC on S100B secretion in primary astrocyte cultures, acute hippocampal slices and C6 glioma cells, as well as lactate mediation. Our results demonstrated that C6 responded similarly to astrocytes in various parameters, despite the decrease in S100B secretion, which was inversely observed in astrocytes and slices. Furthermore, FC inversely altered extracellular lactate in both models, suggesting a role for lactate in S100B secretion. This was reinforced by a decrease in S100B secretion in hippocampal slices treated with lactate and its agonist, but not in C6 cells, despite HCAR1 expression. Our findings indicate that extracellular lactate mediates the decrease in S100B secretion in astrocytes exposed to FC. They also emphasize the differences in C6 glioma cells regarding energetic metabolism. The proposed mechanism via HCAR1 provides further compelling evidence of the relationship between S100B and glucose metabolism.

Polypill use for the prevention of cardiovascular disease: A position paper.

Cardiovascular (CV) guidelines stress the need for global intervention to manage risk factors and reduce the risk of major vascular events. Growing evidence supports the use of polypill as a strategy to prevent cerebral and cardiovascular disease, however it is still underused in clinical practice. This paper presents an expert consensus aimed to summarize the data regarding polypill use. The authors consider the benefits of polypill and the significant claims for clinical applicability. Potential advantages and disadvantages, data regarding several populations in primary and secondary prevention, and pharmacoeconomic data are also addressed.

Prevalence of latent tuberculosis infection among patients with interstitial lung disease requiring immunosuppression.

OBJECTIVE: To characterize the prevalence of latent tuberculosis infection (LTBI) in patients with interstitial lung diseases (ILDs) requiring immunosuppression. Only 5 to 10% of individuals infected with Mycobacterium tuberculosis develop tuberculosis, and certain groups of patients have an increased risk of illness, such as the immunocompromised. Patients with ILDs are frequently treated with immunosuppressants and, therefore, might have a higher risk of developing the disease. METHODS: Prospective study conducted at the ILD reference center of the Federal University of Paraná from January 2019 to December 2020. The screening of LTBI was performed with the use of the tuberculin skin test (TST). RESULTS: The sample consisted of 88 patients, of whom 64.8% were women, with a mean age of 61.4 years. The most frequent diagnoses were autoimmune rheumatic disease ILD (38.6%) and hypersensitivity pneumonitis (35.2%). The most common immunosuppressant in use at the time of the TST was prednisone, either in combination with mycophenolate (19.3%) or alone (17.1%). The majority of participants had fibrotic lung disease, characterized by a reticular interstitial pattern on chest computed tomography (79.5%) and moderate to severe functional impairment (mean FVC 69.2%). A prevalence of LTBI of 9.1% (CI 95%, 2.1%-15.1%) was found, with a TST median of 13. CONCLUSION: Patients with ILD who are treated with immunosuppressants are not commonly screened for LTBI, despite being under a greater risk of progression to active disease. This study suggests the need for a more cautious approach to these patients.

Profile of patients with post-tuberculosis bronchiectasis in a tertiary care hospital in Brazil.

Bronchiectasis are abnormal permanently dilated bronchi which lead to chronic cough and other respiratory symptoms. Though tuberculosis (TB) is a common cause of bronchiectasis, data on this association are scarce. The objective of this study was to describe the profile of patients with post-TB bronchiectasis at a tertiary hospital in the southern region of Brazil. This was a retrospective study with data from patients in follow-up at our hospital from January 2005 to December 2020. We included patients 14 years of age or older who had bronchiectasis on chest computed tomography and a history of pulmonary TB. We excluded patients with bronchiectasis due to other causes or with confirmed non-tuberculous mycobacteria infection. We included 54 of the 204 non-cystic fibrosis bronchiectasis patients seen at our hospital during the study period. Most of the patients were female, older, and non-smokers. Less than a third had chronic bronchial infection by some agent. More than two thirds had some type of ventilatory defect, the most common being obstruction. More than half had upper-lobe impairment. Severity of the disease seemed to be equally distributed from mild to severe. Treatment was varied, including bronchodilators, inhaled corticosteroids, and azithromycin. We found that the profile of patients in our hospital is similar to that described in other studies, with slight differences in regard to microbiology and treatment.

Acute Methylglyoxal-Induced Damage in Blood-Brain Barrier and Hippocampal Tissue.

Methylglyoxal (MG) is a reactive dicarbonyl compound formed mostly via the glycolytic pathway. Elevated blood glucose levels can cause MG accumulation in plasma and cerebrospinal fluid in patients with diabetes mellitus and Alzheimer's disease. Under these disease conditions, the high reactivity of MG leads to modification of proteins and other biomolecules, generating advanced glycation end products (AGEs), which are considered mediators in neurodegenerative diseases. We investigated the integrity of the blood-brain barrier (BBB) and astrocyte response in the hippocampus to acute insult induced by MG when it was intracerebroventricularly administered to rats. Seventy-two hours later, BBB integrity was lost, as assessed by the entry of Evans dye into the brain tissue and albumin in the cerebrospinal fluid, and a decrease in aquaporin-4 and connexin-43 in the hippocampal tissue. MG did not induce changes in the hippocampal contents of RAGE in this short interval, but decreased the expression of S100B, an astrocyte-secreted protein that binds RAGE. The expression of two important transcription factors of the antioxidant response, NF-κB and Nrf2, was unchanged. However, hemeoxigenase-1 was upregulated in the MG-treated group. These data corroborate the idea that hippocampal cells are targets of MG toxicity and that BBB dysfunction and specific glial alterations induced by this compound may contribute to the behavioral and cognitive alterations observed in these animals.

High-Flow Nasal Cannula Therapy in Patients With COVID-19: Predictive Response Factors.

BACKGROUND: COVID-19 pneumonia has been responsible for many ICU patients' admissions with hypoxemic respiratory failure, and oxygen therapy is one of the pillars of its treatment. The current pandemic scenario has limited the availability of ICU beds and access to invasive ventilation equipment. High-flow nasal cannula (HFNC) can reduce the need for orotracheal intubation compared with conventional oxygen therapy, providing better results than noninvasive respiratory support. However, HFNC use has been controversial due to concerns about the benefits and risks of aerosol dispersion. In this context, we evaluated the performance of the HFNC therapy in patients with COVID-19 and investigated factors that can predict favorable responses. METHODS: A prospective observational study was conducted, which included hospitalized adult subjects with COVID-19 in the respiratory wards who needed oxygen therapy. Clinical and laboratory parameters were collected to compare HFNC therapy use and the outcomes. RESULTS: In 6 months, 128 subjects were included and the success rate of HFNC therapy was 53%. Logistic regression analysis showed that the Charlson comorbidity score, need for oxygen flow, [Formula: see text], and breathing frequency predicted therapy failure. The mortality rate increased among the non-responders versus the responders (47% vs 3%), 48% of failure occurred in the first 24 h of the HFNC therapy. A ROX (respiratory frequency - oxygenation) index > 4.98 in 6 h and > 4.53 in 24 h predicted success of the HFNC therapy with an area under the curve of 0.7, and a ROX index < 3.47 predicted failure with 88% of specificity. CONCLUSIONS: HFNC in the subjects with COVID-19 was associated with reduced mortality and improved oxygenation in the subjects with respiratory distress. Close monitoring of specific parameters defines eligible patients and rapidly identifies those in need of invasive ventilatory support.

Prevalence of latent tuberculosis infection among patients with interstitial lung disease requiring immunosuppression / Prevalência de infecção latente por tuberculose em pacientes com doença pulmonar intersticial com necessidade de imunossupressão

ABSTRACT Objective To characterize the prevalence of latent tuberculosis infection (LTBI) in patients with interstitial lung diseases (ILDs) requiring immunosuppression. Only 5 to 10% of individuals infected with Mycobacterium tuberculosis develop tuberculosis, and certain groups of patients have an increased risk of illness, such as the immunocompromised. Patients with ILDs are frequently treated with immunosuppressants and, therefore, might have a higher risk of developing the disease. Methods Prospective study conducted at the ILD reference center of the Federal University of Paraná from January 2019 to December 2020. The screening of LTBI was performed with the use of the tuberculin skin test (TST). Results The sample consisted of 88 patients, of whom 64.8% were women, with a mean age of 61.4 years. The most frequent diagnoses were autoimmune rheumatic disease ILD (38.6%) and hypersensitivity pneumonitis (35.2%). The most common immunosuppressant in use at the time of the TST was prednisone, either in combination with mycophenolate (19.3%) or alone (17.1%). The majority of participants had fibrotic lung disease, characterized by a reticular interstitial pattern on chest computed tomography (79.5%) and moderate to severe functional impairment (mean FVC 69.2%). A prevalence of LTBI of 9.1% (CI 95%, 2.1%-15.1%) was found, with a TST median of 13. Conclusion Patients with ILD who are treated with immunosuppressants are not commonly screened for LTBI, despite being under a greater risk of progression to active disease. This study suggests the need for a more cautious approach to these patients.

RESUMO Objetivo Caracterizar a prevalência de Infecção Latente por Tuberculose (ILTB) em pacientes com Doenças Pulmonares Intersticiais (DPIs) que necessitam de imunossupressão. Apenas 5 a 10% dos indivíduos infectados pelo Mycobacterium tuberculosis desenvolvem tuberculose, sendo que certos grupos de pacientes apresentam maior risco de doença, tais como os imunocomprometidos. Pacientes com DPIs são frequentemente tratados com imunossupressores, portanto, podem apresentar maior risco de desenvolver a doença. Métodos Estudo prospectivo conduzido no Centro de Referência para DPI da Universidade Federal do Paraná (UFPR), entre Janeiro de 2019 e Dezembro de 2020. O rastreio de ILTB foi realizado por meio da Prova Tuberculínica (PT). Resultados A amostra foi composta por 88 pacientes, dos quais 64,8% eram mulheres, com, em média, 61,4 anos de idade. Os diagnósticos mais frequentes foram DPI associada a doença reumática autoimune (DRAI) (38,6%) e pneumonite de hipersensibilidade (35,2%). Prednisona foi o imunossupressor mais comumente utilizado à época da PT, em combinação com micofenolato (19,3%) ou isoladamente (17,1%). A maioria dos participantes tinha doença pulmonar fibrótica, caracterizada por infiltrado reticular em tomografia computadorizada de tórax (79,5%), bem como comprometimento funcional moderado a grave (Capacidade Vital Forçada (CVF) média de 69,2%). Observou-se uma prevalência de ILTB de 9,1% (Intervalo de Confiança (IC) 95%, 2,1%-15,1%), com mediana da PT de 13. Conclusão Não é comum que pacientes com DPI tratados com imunossupressores sejam avaliados quanto à presença de ILTB, apesar de estarem sob um maior risco de progressão para doença ativa. Este estudo sugeriu a necessidade de uma abordagem mais cuidadosa em relação a esses pacientes.

Identification of the most relevant factors that affect and reflect the quality of granules by application of canonical and cluster analysis.

The production of granules by wet granulation in a fluidized bed was assessed according to two statistical techniques to identify the most relevant factors that affect the quality of the granules. The statistics used include Canonical Analysis and Cluster Analysis. The factors studied, according to a center of gravity design, included the solubility of a model drug, different grades of polyvinylpirrolidone (PVP), the polarity and the rate of administration of the granulation solution, the atomizing air pressure, the inlet air pressure and rate. The properties of the granules considered were the yield, the assay of the drug, the size, the densities (true, bulk and tapped), the friability, the flowability and one compressibility index. Statistical analysis of the factors evaluated has shown that the solubility of the materials and the pressure of the atomizing air in the nozzle were the most critical parameters affecting the quality of the granules. Less relevant were the granulation solution and the grade of PVP. The properties of the granules that best described their quality were the yield and the densities. From the Cluster Analysis it was possible to divide the granules in two clusters, where cluster 1 was identifiable by the yield, the assay, the flowability, and the friability, whereas cluster 2 was better identified by the size of the granules.