Building the Momentum for A Stronger Pharmaceutical System in Africa.

Despite impressive progress, nearly two billion people worldwide have no access to essential medicines. The COVID-19 pandemic revealed Africa's vulnerability due to its reliance on imports for most vaccines, medicines, and other health product needs. The vaccine manufacturing is complex and requires massive financial investments, with global, regional, and national regulatory structures introducing consistent and urgent reforms to assure the quality and safety of medicines. In 2020, there were approximately 600 pharmaceutical manufacturers in Africa, 80% of which were concentrated in eight countries: Egypt, Algeria, Morocco, Tunisia, Nigeria, Ghana, Kenya, and South Africa. Only 4 countries had more than 50 manufacturers, while 22 countries had no local production. Out of the 600, around 25% were multinational companies. Africa is equally affected by modest scaled capacities substantially engaging in packaging and labelling, and occasionally fill and finish steps, facing criticalities in terms of solvent domestic markets. This article discusses the challenges in the development of a local pharmaceutical manufacturing in Africa and reflects on the importance of the momentum for strengthening the local medical production capacity in the continent as a critical opportunity for advancing universal health coverage (UHC).

H2S donating corticosteroids: Design, synthesis and biological evaluation in a murine model of asthma.

Introduction: Hydrogen sulfide (H2S) is a fundamental biological endogenous gas-mediator in the respiratory system. It regulates pivotal patho-physiological processes such as oxidative stress, pulmonary circulation, airway tone and inflammation. Objectives: We herein describe the design and synthesis of molecular hybrids obtained by the condensation of several corticosteroids with different hydrogen sulfide releasing moieties. Methods: All the molecules are characterized for their ability to release H2S both via amperometric approach and using a fluorescent probe. The chemical stability of the newly synthesized hybrid molecules has been investigated at differing pH values and in human serum. Results: Prednisone-TBZ hybrid (compound 7) was selected for further evaluations. The obtained results from the in vitro and in vivo studies clearly show evidence in favor of the anti-inflammatory properties of the released H2S. Conclusions: The protective effect on airway remodeling makes the hybrid Prednisone-TBZ (compound 7) as a promising therapeutic option in reducing allergic asthma symptoms and exacerbations.

[Acute pancreatitis in pediatrics as a complication of multi-systemic inflammatory syndrome associated with COVID-19: A case report]. / Pancreatitis aguda en pediatría como complicación de síndrome inflamatorio multisistémico asociado a COVID-19: un caso clínico.

In April 2020, UK studies informed a condition in children similar to incomplete Kawasaki disease or toxic shock syndrome. From that time onwards, papers on children suffering from similar conditions have been published in different parts of the world. Today the disease is named multisystem inflammatory syndrome in children (MIS-C) associated with Covid-19. Acute pancreatitis was reported mainly in adult patients with acute SARS-COV-2 infection developing direct cytopathic effect or immune-mediated and systemic inflammatory indirect cellular responses. However, there are only a few studies, which describe the acute pancreatitis case during MIS-C period. The present article describes the clinical presentation, therapy and evolution of a 9 years-old female patient developing an acute pancreatitis case suffering from MIS-C.

En abril de 2020, en informes provenientes del Reino Unido se notificó una presentación en niños similar a la enfermedad de Kawasaki incompleta o al síndrome de choque tóxico asociados con la enfermedad por el nuevo coronavirus (COVID-19). Desde entonces, ha habido informes de niños afectados de manera similar en otras partes del mundo. En la actualidad, la afección se ha denominado síndrome inflamatorio multisistémico asociado a COVID-19 en niños (SIM-C). Por otra parte, se notificaron casos de pancreatitis aguda, en su mayoría en pacientes adultos, en el contexto de la infección aguda por el coronavirus 2 causante del síndrome respiratorio agudo grave (SARS-COV-2), causada por efectos citopáticos directos o respuestas celulares indirectas sistémicas inflamatorias e inmunomediadas. Sin embargo, son escasas las notificaciones en las que se describe el cuadro de pancreatitis aguda durante el SIM-C. Se describe aquí la presentación clínica, el tratamiento y la evolución de una paciente de 9 años que presen.

Home parenteral nutrition patients on mixed oil lipid emulsion have a higher rate of hospitalizations compare to those on soybean oil- a prospective 2-year cohort study.

BACKGROUND & AIMS: Mixed oil intravenous lipid emulsion (MO ILE) that contains 30% soybean oil (SO), 30% medium chain triglycerides, 25% olive oil and 15% fish oil can benefit hospitalized patients receiving parenteral nutrition (PN) but there are very few studies on its long-term use. Our goal was to evaluate the clinical outcomes of adults receiving home PN (HPN) with MO versus those receiving SO ILE over a 2-year period. METHOD: This is a retrospective analysis of data collected prospectively from a cohort of patients recorded in the Canadian HPN Registry over a 2-year period. HPN patients from academic programs across Canada were entered in the Registry according to a validated protocol. For this study, demographic, nutritional, laboratory and clinical data were extracted from January 1st 2015, when MO lipid emulsion became available in Canada, to July 24th 2019. Clinical data for each patient included: number of hospitalizations, number of hospitalizations related to HPN and number of hospitalization days related to HPN, over a year; incidence of line sepsis per 1000 catheter days and mortality. Data are presented as median (1st, 3rd quartile) for continuous variables and frequency (percentage) for categorical variables. Comparisons between groups were performed using two sample t-test or Wilcoxon Rank Sum tests for continuous variables and Chi-square tests or Fisher's exact tests for categorical variables. Univariate and multiple linear regressions were also carried out. Statistical significance is set at a p-value <0.05. RESULTS: A total of 120 patients were included (MO n = 68, SO n = 52). Significant differences at baseline between the two groups were a higher use of Hickman line (62.12% vs 42%, p = 0.038) and more western Canada based hospital care with MO (75% vs 42.31%, p = 0.0002). The MO group had significantly more hospitalizations (p = 0.001), more hospitalizations related to HPN (p = 0.012) and more hospitalization days related to HPN (p = 0.016) per patient per year compared to SO patients. There was no significant difference between groups for line sepsis per 1000 catheter days (MO: 0.05 (0.0, 1.0) vs SO: 0.0 (0.0, 0.22), p = 0.053) or mortality. All other variables, including biochemical variables, were similar between groups. In a multiple regression analysis, the following factors were significantly associated with a greater number of hospitalizations per patient per year: use of MO, high blood glucose from the last recorded value and having died by the end of the study period. CONCLUSION: This 2-year prospective cohort study suggests an increased risk of hospitalization in HPN patients receiving MO lipid emulsion. The long-term effect of using MO lipid emulsion in HPN patients should be further evaluated using a large randomized controlled trial. THE STUDY WAS REGISTERED IN CLINICALTRIALS.GOV: (NCT02299466).

Pancreatitis aguda en pediatría como complicación de síndrome inflamatorio multisistémico asociado a COVID-19: un caso clínico / Acute pancreatitis in pediatrics as a complication of multi-systemic inflammatory syndrome associated with COVID-19: A case report

En abril de 2020, en informes provenientes del Reino Unido se notificó una presentación en niños similar a la enfermedad de Kawasaki incompleta o al síndrome de choque tóxico asociados con la enfermedad por el nuevo coronavirus (COVID-19). Desde entonces, ha habido informes de niños afectados de manera similar en otras partes del mundo. En la actualidad, la afección se ha denominado síndrome inflamatorio multisistémico asociado a COVID-19 en niños (SIM-C). Por otra parte, se notificaron casos de pancreatitis aguda, en su mayoría en pacientes adultos, en el contexto de la infección aguda por el coronavirus 2 causante del síndrome respiratorio agudo grave (SARS-COV-2), causada por efectos citopáticos directos o respuestas celulares indirectas sistémicas inflamatorias e inmunomediadas. Sin embargo, son escasas las notificaciones en las que se describe el cuadro de pancreatitis aguda durante el SIM-C. Se describe aquí la presentación clínica, el tratamiento y la evolución de una paciente de 9 años que presentó un cuadro de pancreatitis aguda en el contexto del SIM-C.

In April 2020, UK studies informed a condition in children similar to incomplete Kawasaki disease or toxic shock syndrome. From that time onwards, papers on children suffering from similar conditions have been published in different parts of the world. Today the disease is named multisystem inflammatory syndrome in children (MIS-C) associated with Covid-19. Acute pancreatitis was reported mainly in adult patients with acute SARS-COV-2 infection developing direct cytopathic effect or immune-mediated and systemic inflammatory indirect cellular responses. However, there are only a few studies, which describe the acute pancreatitis case during MIS-C period. The present article describes the clinical presentation, therapy and evolution of a 9 years-old female patient developing an acute pancreatitis case suffering from MIS-C

Mitochondrial proteomics investigation of a cellular model of impaired dopamine homeostasis, an early step in Parkinson's disease pathogenesis.

Impaired dopamine homeostasis is an early event in the pathogenesis of Parkinson's disease. Generation of intracellular reactive oxygen species consequent to dopamine oxidation leads to mitochondrial dysfunction and eventually cell death. Alterations in the mitochondrial proteome due to dopamine exposure were investigated in the SH-SY5Y human neuroblastoma cell line. The combination of two orthogonal proteomic approaches, two-dimensional electrophoresis and shotgun proteomics (proteomeXchange dataset PXD000838), was used to highlight the specific pathways perturbed by the increase of intracellular dopamine, in comparison with those perturbed by a specific mitochondrial toxin (4-methylphenylpyridinium, MPP(+)), a neurotoxin causing Parkinsonism-like symptoms in animal models. Proteins altered by MPP(+) did not completely overlap with those affected by dopamine treatment. In particular, the MPP(+) target complex I component NADH dehydrogenase [ubiquinone] iron-sulfur protein 3 was not affected by dopamine together with 26 other proteins. The comparison of proteomics approaches highlighted the fragmentation of some mitochondrial proteins, suggesting an alteration of the mitochondrial protease activity. Pathway and disease association analysis of the proteins affected by dopamine revealed the overrepresentation of the Parkinson's disease and the parkin-ubiquitin proteasomal system pathways and of gene ontologies associated with generation of precursor metabolites and energy, response to topologically incorrect proteins and programmed cell death. These alterations may be globally interpreted in part as the result of a direct effect of dopamine on mitochondria (e.g. alteration of the mitochondrial protease activity) and in part as the effect on mitochondria of a general activation of cellular processes (e.g. regulation of programmed cell death).