Matrix metalloproteinases are associated with severity of disease among COVID-19 patients: A possible pharmacological target.

COVID-19 is a devastating disease and imbalanced matrix metalloproteinase (MMP) activity may contribute to its pathophysiology. This exploratory study examined whether increased circulating concentrations of MMP-2 and MMP-9, and their endogenous inhibitors, the tissue inhibitors of MMP (TIMP)-1, TIMP-2, TIMP-3 and TIMP-4 are persistently found in patients 2 weeks after their recovery from severe or critical COVID-19 as compared with those in healthy controls. Subjects who had severe (n = 26) or critical (n = 25) PCR-confirmed COVID-19 and healthy controls (n = 21) had blood samples drawn 2 weeks after recovery and serum MMP-2, MMP-9, TIMP-1, TIMP-2, TIMP-3 and TIMP-4 were determined using two Human Luminex® Discovery Assays. Circulating MMP activity was also determined by gel zymography. Patients who had severe or critical COVID-19 had increased circulating MMP-9 and MMP-2 concentrations, with increased MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios indicating increased MMP activity, confirmed by gel zymography (all p < 0.05). Higher circulating MMP-9 (but not MMP-2) concentrations were found in critical versus severe COVID-19 (p < 0.05). We found increased circulating MMP-9 and MMP-2 concentrations and activity many days after recovery from the acute disease, with MMP-9 levels associated with disease severity. These biochemical alterations suggest that MMP-2 and MMP-9 may be important pharmacological targets in COVID-19.

Exercise and pyridostigmine prevents gastric emptying delay and increase blood pressure and cisplatin-induced baroreflex sensitivity in rats.

Cisplatin treatment induces an autonomic dysfunction and gastrointestinal and cardiovascular disorders. Physical exercise as well as pyridostigmine treatment induces improves in the autonomic nervous system. In the current study, we investigated the effect of physical exercise and pyridostigmine treatment on gastrointestinal and cardiovascular changes in cisplatin-treated rats. Rats were divided into groups: Saline (S), Cisplatin (Cis), Exercise (Ex), Cisplatin+Exercise (Cis+Ex), Pyridostigmine (Pyr), and Cisplatin+Pyridostigmine (Cis+Pyr). We induced gastrointestinal dysmotility by administering 3 mg kg-1 of cisplatin once week for 5 weeks. The Ex was swimming (1 h per day/5 days per week for 5 weeks with 5% b.w.). GE was evaluated through the colorimetric method of fractional red phenol recovery 10 min after feeding. Pyr groups received 1.5 mg kg-1, p.o. or concomitant Cis treatment. Moreover, gastric contraction in vitro and hemodynamic parameters such as MAP, HR, and evoked baroreflex sensitivity were assessed, as well as sympathetic and parasympathetic tone and intrinsic heart rate (IHR). Cis decrease GE vs. saline (p<0.05). Cis+Ex or Cis+Pyr prevented (p<0.05) decrease in GE vs. Cis rats. Cis decreased (p<0.05) gastric responsiveness in vitro vs. saline. Cis+Ex or Cis+Pyr prevented this phenomenon. Cis treatment increase MAP and decrease in HR (p<0.05) vs saline. Cis+Ex or Cis+Pyr attenuated (p<0.05) both alterations. Cis increased sympathetic tone and decreased vagal tone and IHR (p<0.05) vs. the saline. Cis+Ex or Cis+Pyr prevented those effects vs. the Cis group. In conclusion, physical exercise and pyridostigmine treatment improves autonomic dysfunction and prevented GE delay and changes in hemodynamic parameters, baroreflex sensitivity, and cardiac autonomic control in cisplatin-treated rats.

Acetylcholinesterase inhibition prevents alterations in cardiovascular autonomic control and gastric motility in L-NAME-induced hypertensive rats.

AIMS: Autonomic dysfunction in arterial hypertension affects cardiorespiratory control and gastric motility and has been characterized by increased sympathetic and reduced parasympathetic activity. In the present work we investigated the effects of anticholinesterase drugs [donepezil (DON) or pyridostigmine (PYR)] on cardiovascular, autonomic, and gastric parameters in L-NAME-induced hypertensive rats. MATERIALS AND METHODS: Daily oral gavage of L-NAME (70 mg/kg/day) was performed over 14 days in male Wistar rats (180-220 g), whereas daily oral gavage of DON or PYR (1.6 and 22 mg/kg/day, respectively) started 2 days after the L-NAME treatment initiation and lasted 12 days. The development of hypertension was verified by tail plethysmography technique. After the end of treatments, the animals were subjected to experimental protocols (6-12 animals per group; total number of animals used: 78). KEY FINDINGS: L-NAME hypertensive animals had no alterations in heart rate (HR) and intrinsic HR, but showed reduction in baroreflex sensitivity, parasympathetic tone, and gastric motility; and the sympathetic tone, chemoreflex sensitivity, and the LF (low frequency) band of systolic arterial pressure (SAP) variability were increased. DON or PYR attenuated the increase in mean arterial pressure (MAP) induced by L-NAME. Both anticholinesterase drugs were effective in preventing the decrease in baroreflex sensitivity, parasympathetic tone and gastric motility, and also prevented the increases in peripheral chemoreflex response and cardiac sympathetic tone. SIGNIFICANCE: Acetylcholinesterase inhibition with DON or PYR is a promising pharmacological approach to increase parasympathetic function, thus preventing the hypertension-induced alterations in the cardiovascular, gastrointestinal and autonomic systems.

Cellular changes diagnosed by cérvico-vaginal cytology in a public health laboratory of Teresina-PI / Alterações celulares diagnosticadas por meio da citologia cervico-vaginal no laboratório de saúde pública de Teresina-PI

Objective: to verify the frequency of cellular alterations of the female genital tract of women assisted by a public clinical laboratory in Teresina ­ Piaui in 2016, as well as to evaluate the relation between patients' education levels and the frequency of atypia found. Methodology: data from the 9040 forms of cervical-vaginal oncocytology (SUS standard) from the 2016 year were collected. Results: 9040 reports were analyzed, among which 8,095 (89.55%) had negative and 945 (10.45%) were positive to oncologic abnormalities. It was identified squamous cells of indeterminate significance with 5.84%, low-grade intraepithelial lesions (LSIL) with 1,97%, high-grade intraepithelial lesions (HSIL) 1.33%, glandular cell atypia (ACG) with 1.25% and invasive squamous cell carcinoma 0.06%. Regarding the level of schooling, women who attended elementary and high school corresponded to the higher percentage of patients. Conclusion: it is concluded that the incidence of atypia was considerably higher than described in the previous literature. Thus, it is recommended the adoption of strategies to improve the adherence and the awareness of the population regarding the necessity of this exam.

Objetivo: verificar a frequência das alterações celulares do trato genital feminino que acometeram mulheres atendidas no ano de 2016 em um laboratório clínico público em Teresina-PI, avaliar a frequência dos níveis de escolaridade das pacientes e correlacionar com a frequência das atipias encontradas. Metodologia: os dados foram coletados a partir das fichas de requisição de exame citopatológico do colo do útero (padrão SUS), referentes ao ano de 2016. Resultados: dos 9040 laudos analisados, 8.095 (89,55%), tiveram citologia negativa para as alterações oncológicas e 945 (10,45%) foram positivos. Estes ficaram assim distribuídos: células escamosas de significado indeterminados com 5,84%, as lesões intra-epiteliais de baixo grau (LSIL) com 1,97%, lesões intra-epiteliais de alto grau (HSIL) com 1,33%, atipias de significado indeterminado em células glandulares (ACG) com 1,25% e carcinoma epidermóide invasor com 0,06%. No que se refere ao grau de escolaridade, maior frequência foi observada entre pacientes que frequentaram o ensino fundamental e médio. Conclusão: os resultados permitiram concluir que a incidência das atipias foi muito além das observadas na literatura. Para equacionar esse problema, o país deve adotar estratégias que visem a adesão e a conscientização da população sobre a necessidade do exame.