Organization of public entities to attend to the judicialization of access to medications in the state of Santa Catarina, Brazil. / Organização dos entes públicos para atender a judicialização do acesso a medicamentos no estado de Santa Catarina, Brasil.

This study describes the organization of the State of Santa Catarina (SC), Brazil, to attend to the judicialization of access to medications from the early 2000s to 2018. Document analysis and interviews with representatives of the Executive, the Judiciary, the State Attorney General Office (PGE, Procuradoria Geral do Estado/SC), the Public Defender's Office of the State of SC and the Public Prosecutor's Office of the State of SC (MPSC, Ministério Público de SC) were performed. The Judiciary, the PGE/SC and the MPSC organized themselves to address the phenomenon. Initially, the State Health Secretariat did not have an organization to attend to the judicialization; with the increase in the number of lawsuits, it created sectors, routines and systems, and at the end of 2018 there was a specific Administrative Management and sector. The main measures used were: public hearing of the Federal Supreme Court, statements by the National Justice Council, Incident of Resolution of Repetitive Demands, State Monitoring and Resolution Committee for Health Care Demands in SC, Center for Repetitive Actions in Health Care, Multidisciplinary Judicial Support Commission and the Technical Support Center. The judicialization of access to medications in SC has not yet been resolved, since all the implemented measures have not prevented the increasing rise in expenses with lawsuits.

Esse estudo descreve a organização do Estado de Santa Catarina (SC) para atender a judicialização do acesso a medicamentos do início dos anos 2000 a 2018. Foi feita análise documental e entrevistas com representantes do Executivo, do Judiciário, da Procuradoria Geral do Estado (PGE/SC), da Defensoria Pública do Estado de SC e do Ministério Público de SC (MPSC). O Judiciário, a PGE/SC e o MPSC se organizaram para abordar o fenômeno. Inicialmente, a Secretaria de Estado da Saúde não possuía uma organização para atender a judicialização; com o aumento do número de processos, criou setores, rotinas e sistemas, e ao final de 2018 havia uma Gerência e um setor específicos. As principais medidas utilizadas foram: Audiência Pública do Supremo Tribunal Federal, enunciados do Conselho Nacional de Justiça, Incidente de Resolução de Demanda Repetitiva, Comitê Estadual de Monitoramento e Resolução das Demandas de Assistência da Saúde de SC, Núcleo de Ações Repetitivas em Assistência à Saúde, Comissão Multidisciplinar de Apoio Judicial e Núcleo de Apoio Técnico. O fenômeno da judicialização do acesso a medicamentos em SC ainda não está bem solucionado, visto que todas as medidas implantadas não evitaram o aumento crescente dos gastos com as ações judiciais.

Organização dos entes públicos para atender a judicialização do acesso a medicamentos no estado de Santa Catarina, Brasil / Organization of public entities to attend to the judicialization of access to medications in the state of Santa Catarina, Brazil

Resumo Esse estudo descreve a organização do Estado de Santa Catarina (SC) para atender a judicialização do acesso a medicamentos do início dos anos 2000 a 2018. Foi feita análise documental e entrevistas com representantes do Executivo, do Judiciário, da Procuradoria Geral do Estado (PGE/SC), da Defensoria Pública do Estado de SC e do Ministério Público de SC (MPSC). O Judiciário, a PGE/SC e o MPSC se organizaram para abordar o fenômeno. Inicialmente, a Secretaria de Estado da Saúde não possuía uma organização para atender a judicialização; com o aumento do número de processos, criou setores, rotinas e sistemas, e ao final de 2018 havia uma Gerência e um setor específicos. As principais medidas utilizadas foram: Audiência Pública do Supremo Tribunal Federal, enunciados do Conselho Nacional de Justiça, Incidente de Resolução de Demanda Repetitiva, Comitê Estadual de Monitoramento e Resolução das Demandas de Assistência da Saúde de SC, Núcleo de Ações Repetitivas em Assistência à Saúde, Comissão Multidisciplinar de Apoio Judicial e Núcleo de Apoio Técnico. O fenômeno da judicialização do acesso a medicamentos em SC ainda não está bem solucionado, visto que todas as medidas implantadas não evitaram o aumento crescente dos gastos com as ações judiciais.

Abstract This study describes the organization of the State of Santa Catarina (SC), Brazil, to attend to the judicialization of access to medications from the early 2000s to 2018. Document analysis and interviews with representatives of the Executive, the Judiciary, the State Attorney General Office (PGE, Procuradoria Geral do Estado/SC), the Public Defender's Office of the State of SC and the Public Prosecutor's Office of the State of SC (MPSC, Ministério Público de SC) were performed. The Judiciary, the PGE/SC and the MPSC organized themselves to address the phenomenon. Initially, the State Health Secretariat did not have an organization to attend to the judicialization; with the increase in the number of lawsuits, it created sectors, routines and systems, and at the end of 2018 there was a specific Administrative Management and sector. The main measures used were: public hearing of the Federal Supreme Court, statements by the National Justice Council, Incident of Resolution of Repetitive Demands, State Monitoring and Resolution Committee for Health Care Demands in SC, Center for Repetitive Actions in Health Care, Multidisciplinary Judicial Support Commission and the Technical Support Center. The judicialization of access to medications in SC has not yet been resolved, since all the implemented measures have not prevented the increasing rise in expenses with lawsuits.

Temporal development of neurochemical and cognitive impairments following reserpine administration in rats.

The systemic administration of low reserpine (RES) doses (0.1-1.0 mg/kg) has been proposed as a valuable rat model for the study of non-motor symptoms of Parkinson's disease (PD). Here, we investigated the temporal-dependent effects of RES (1 mg/kg, s.c.) on short-term memory and locomotion, as well as, the levels of dopamine, serotonin and its metabolites in the striatum, hippocampus and prefrontal cortex at 3, 24 or 72 h after RES administration. RES administrations resulted in social and object recognition memory impairment and increased dopamine turnover in the striatum, without changes in the rat spontaneous locomotor activity, 3 h after RES administration. Altogether, these results provide new insights for the use of RES administration as an experimental design for the study of PD non-motor symptoms in rats.

The Gender-Biased Effects of Intranasal MPTP Administration on Anhedonic- and Depressive-Like Behaviors in C57BL/6 Mice: the Role of Neurotrophic Factors.

Depression is a highly prevalent and debilitating non-motor symptom observed during the early stages of Parkinson's disease (PD). Although PD prevalence is higher in men, the depressive symptoms in PD are more common in women. Therefore, the aim of this study was to investigate the development of anhedonic- and depressive-like behaviors in male and female mice and the potential mechanisms related to depressive symptoms in an experimental model of PD. Young adult male and female C57BL/6 mice (3 months old) received a single intranasal (i.n.) administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and were submitted to a battery of behavioral tasks (sucrose consumption, splash test, tail suspension, forced swimming and open field tests) to assess their emotional and motor profiles. Considering the role of sexual hormones in emotional behaviors, the same protocol of i.n. MPTP administration and the splash, tail suspension, and open field tests were conducted in ovariectomized (OVX) and aged C57BL/6 female (20 months old) mice. We also investigated the immunocontent of neurotrophins (BDNF, GDNF, and VEGF) in the hippocampus and prefrontal cortex by western blot. I.n.  MPTP administration induced more pronounced anhedonic- and selective depressive-like behaviors in female adult mice, also observed in OVX and aged female mice, with the absence of motor impairments. Furthermore, MPTP induced a more pronounced depletion of neurotrophins in the prefrontal cortex and hippocampus in female than male mice. This study provides new evidence of increased susceptibility of female mice to anhedonic- and depressive-like behaviors following i.n. MPTP administration. The observed gender-related effects of MPTP on emotional parameters seem to be linked to increased depletion of neurotrophins (particularly BDNF and GDNF) in the hippocampus and prefrontal cortex of female mice.

Moderate traumatic brain injury increases the vulnerability to neurotoxicity induced by systemic administration of 6-hydroxydopamine in mice.

Moderate traumatic brain injury (TBI) might increase the vulnerability to neuronal neurodegeneration, but the basis of such selective neuronal susceptibility has remained elusive. In keeping with the disruption of the blood-brain barrier (BBB) caused by TBI, changes in BBB permeability following brain injury could facilitate the access of xenobiotics into the brain. To test this hypothesis, here we evaluated whether TBI would increase the susceptibility of nigrostriatal dopaminergic fibers to the systemic administration of 6-hydroxydopamine (6-OHDA), a classic neurotoxin used to trigger a PD-like phenotype in mice, but that in normal conditions is unable to cross the BBB. Adult Swiss mice were submitted to a moderate TBI using a free weight-drop device and, 5h later, they were injected intraperitoneally with a single dose of 6-OHDA (100mg/kg). Afterwards, during a period of 4weeks, the mice were submitted to a battery of behavioral tests, including the neurological severity score (NSS), the open field and the rotarod. Animals from the TBI plus 6-OHDA group displayed significant motor and neurological impairments that were improved by acute l-DOPA administration (25mg/kg, i.p.). Moreover, the observation of the motor deficits correlates with (i) a significant decrease in the tyrosine hydroxylase levels mainly in the rostral striatum and (ii) a significant increase in the levels of striatal glial fibrillary acidic protein (GFAP) levels. On the whole, the present findings demonstrate that a previous moderate TBI event increases the susceptibility to motor, neurological and neurochemical alterations induced by systemic administration of the dopaminergic neurotoxin 6-OHDA in mice.

Neopterin acts as an endogenous cognitive enhancer.

Neopterin is found at increased levels in biological fluids from individuals with inflammatory disorders. The biological role of this pteridine remains undefined; however, due to its capacity to increase hemeoxygenase-1 content, it has been proposed as a protective agent during cellular stress. Therefore, we investigated the effects of neopterin on motor, emotional and memory functions. To address this question, neopterin (0.4 and/or 4pmol) was injected intracerebroventricularly before or after the training sessions of step-down inhibitory avoidance and fear conditioning tasks, respectively. Memory-related behaviors were assessed in Swiss and C57BL/6 mice, as well as in Wistar rats. Moreover, the putative effects of neopterin on motor and anxiety-related parameters were addressed in the open field and elevated plus-maze tasks. The effects of neopterin on cognitive performance were also investigated after intraperitoneal lipopolysaccharide (LPS) administration (0.33mg/kg) in interleukin-10 knockout mice (IL-10(-/-)). It was consistently observed across rodent species that neopterin facilitated aversive memory acquisition by increasing the latency to step-down in the inhibitory avoidance task. This effect was related to a reduced threshold to generate the hippocampal long-term potentiation (LTP) process, and reduced IL-6 brain levels after the LPS challenge. However, neopterin administration after acquisition did not alter the consolidation of fear memories, neither motor nor anxiety-related parameters. Altogether, neopterin facilitated cognitive processes, probably by inducing an antioxidant/anti-inflammatory state, and by facilitating LTP generation. To our knowledge, this is the first evidence showing the cognitive enhancer property of neopterin.

Effects of Agmatine on Depressive-Like Behavior Induced by Intracerebroventricular Administration of 1-Methyl-4-phenylpyridinium (MPP(+)).

Considering that depression is a common non-motor comorbidity of Parkinson's disease and that agmatine is an endogenous neuromodulator that emerges as a potential agent to manage diverse central nervous system disorders, this study investigated the antidepressant-like effect of agmatine in mice intracerebroventricularly (i.c.v.) injected with the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)). Male C57BL6 mice were treated with agmatine (0.0001, 0.1 or 1 mg/kg) and 60 min later the animals received an i.c.v. injection of MPP(+) (1.8 µg/site). Twenty-four hours after MPP(+) administration, immobility time, anhedonic behavior, and locomotor activity were evaluated in the tail suspension test (TST), splash test, and open field test, respectively. Using Western blot analysis, we investigated the putative modulation of MPP(+) and agmatine on striatal and frontal cortex levels of tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF). MPP(+) increased the immobility time of mice in the TST, as well as induced an anhedonic-like behavior in the splash test, effects which were prevented by pre-treatment with agmatine at the three tested doses. Neither drug, alone or in combination, altered the locomotor activity of mice. I.c.v. administration of MPP(+) increased the striatal immunocontent of TH, an effect prevented by the three tested doses of agmatine. MPP(+) and agmatine did not alter the immunocontent of BDNF in striatum and frontal cortex. These results demonstrate for the first time the antidepressant-like effects of agmatine in an animal model of depressive-like behavior induced by the dopaminergic neurotoxin MPP(+).

Effects of pentylenetetrazole kindling on mitogen-activated protein kinases levels in neocortex and hippocampus of mice.

The epileptogenesis process involves cell signaling events associated with neuroplasticity. The mitogen-activated protein kinases (MAPKs) integrate signals originating from a variety of extracellular stimuli and may regulate cell differentiation, survival, cell death and synaptic plasticity. Here we compared the total and phosphorylated MAPKs (ERK1/2, JNK1/2 and p38(MAPK)) levels in the neocortex and hippocampus of adult Swiss male mice quantified by western blotting analysis 48 h after the last injection of pentylenetetrazole (PTZ), according to the kindling protocol (35 mg/kg, i.p., on alternated days, with a total of eight injections). The total levels of the investigated MAPKs and the phospho-p38(MAPK) in the neocortex and hippocampus were not affected by the PTZ injections. The MAPKs phosphorylation levels remain unaltered in PTZ-treated animals without convulsive seizures. The phospho-JNK2 phosphorylation, but not the phospho-JNK1, was increased in the hippocampus of PTZ-treated animals showing 1-3 days with convulsive seizures, whereas no significant changes were observed in those animals with more than 3 days with convulsive seizures. The phospho-ERK1/2 phosphorylation decreased in the neocortex and increased in the hippocampus of animals with 1-4 days with convulsive seizures and became unaltered in mice that showed convulsive seizures for more than 4 days. These findings indicate that resistance to PTZ kindling is associated with unaltered ERK1/2, JNK1/2 and p38(MAPK) phosphorylation levels in the neocortex and hippocampus. Moreover, when the PTZ kindling-induced epileptogenesis manifests behaviorally, the activation of the different MAPKs sub-families shows a variable and non-linear pattern in the neocortex and hippocampus.