The report emphasizes that sevoflurane is capable of producing excitatory central nervous system (CNS) phenomena in spite of causing primarily CNS depressant effects.
A 33-year-old woman weighing 108 kg with obesity and neurofibromatosis was presented with a 2-year history of poorly controlled hypertension, headaches, palpitations, and occasional chest pain. Her blood pressure was 170/100 mm Hg, and she was treated with daily oral dose of diltiazem (360 mg), hydrodiuril (12.5 mg), lisinopril (20 mg), and metoprolol XL (25 mg) tablets. Biochemical evaluation for pheochromocytoma showed elevated 24-hour urine metanephrine levels of 5496 mcg and normetanephrine level of 6415 mcg. A computed tomographic scan of the abdomen showed a 6 Â 6-cm right adrenal mass. The remainder of her preoperative tests was otherwise normal. Three weeks before surgery, the patient was started on phenoxybenzamine of 10 mg per day orally, which was gradually increased to 30 mg 3 times a day. The day before the planned surgery, the patient was admitted to surgical floor, her average blood pressure and heart rate were 134/76 mm Hg and 65 bpm, respectively. At midnight, she was given an extra dose of 40 mg of phenoxybenzamine and also received 1 L of 5% dextrose with 0.45% normal saline. The following morning patient was taken to the operating room, standard monitors were
Background
The Covid-19 pandemic has emerged as the leading public health challenge of our time (20th century). While vaccinations have finally blunted the death rate, concern has remained about more virulent forms highlighting the need for alternative approaches. Epidemiological studies indicate that physical activity has been shown to decrease the risk of infection of some respiratory viruses. Part of the salutary effects of exercise is believed to be through the elaboration of cytokines by contracting skeletal muscles (termed myokines). The objective of this study was to investigate whether exercise-induced myokines would mitigate the SARS-CoV-2 infectivity of the bronchial epithelium through modulating the SARS-CoV-2 Covid-19 receptor (angiotensin-converting enzyme 2 -ACE2) its priming enzyme, transmembrane serine protease 2 (TMPRSS2).
Methods
We utilized a cell culture model of exercise to generate myokines by differentiating C2C12 cells into myotubules and inducing them to contract via low-frequency electric pulse stimulation. Condition media was concentrated via centrifugation and applied to human immortalized human bronchial epithelium cell line (6HBE14o) along with conditioned media from unstimulated myotubules as controls. Following exposure to myokines, the 16HBE14o cells were harvested and subjected to quantitative RT-PCR and Enzyme-Linked Immunosorbent Assay (ELISA) for assessment of mRNA and protein levels of ACE2 and TMPRSS2, respectively. Pilot proteomic data was performed with isotope barcoding and mass spectroscopy.
Results
Quantitative Real-Time PCR of 16HBE14o with 48 h treated unstimulated vs. stimulated myokine treatment revealed a reduction of ACE2 and TMPRSS2 mRNA by 32% (p<2.69x10-5) and 41% (p<4.57x10-5), respectively. The high sensitivity of ELISAs showed downregulation of ACE2 and TMPRSS2 protein expression in 16HBE14o cells by 53% (p<0.01) and 32% (p<0.03) respectively with 48 h treated. For rigor, this work was replicated in the human lung cancer cell line A549, which mirrored the downregulation. Proteomic analysis showed dramatic alteration in myokine profile between contracted and uncontracted C2C12 tubules.
Conclusions
The current study explores a novel approach of a modified exercise cell culture system and uses ACE2 and TMPRSS2 as a surrogate marker of SARS-CoV-2 infectivity. In conclusion, we demonstrated biological data supporting exercise’s protective effect against Covid-19. These further strengthen myokines’ beneficial role as potential therapeutic targets against SARS-CoV-2 and similar viruses albeit these preliminary cell culture studies will require future validation in animal models.
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