Autophagy in Inflammatory Response against SARS-CoV-2.

The coronavirus disease pandemic, which profoundly reshaped the world in 2019 (COVID-19), and is currently ongoing, has affected over 200 countries, caused over 500 million cumulative cases, and claimed the lives of over 6.4 million people worldwide as of August 2022. The causative agent is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Depicting this virus' life cycle and pathogenic mechanisms, as well as the cellular host factors and pathways involved during infection, has great relevance for the development of therapeutic strategies. Autophagy is a catabolic process that sequesters damaged cell organelles, proteins, and external invading microbes, and delivers them to the lysosomes for degradation. Autophagy would be involved in the entry, endo, and release, as well as the transcription and translation, of the viral particles in the host cell. Secretory autophagy would also be involved in developing the thrombotic immune-inflammatory syndrome seen in a significant number of COVID-19 patients that can lead to severe illness and even death. This review aims to review the main aspects that characterize the complex and not yet fully elucidated relationship between SARS-CoV-2 infection and autophagy. It briefly describes the key concepts regarding autophagy and mentions its pro- and antiviral roles, while also noting the reciprocal effect of viral infection in autophagic pathways and their clinical aspects.

Pancreatic polypeptide: a review of its involvement in neuro-endocrine reflexes, islet-acinar interactions and ethanol-evoked physiopatologic pancreatic gland changes.

prevents, in pancreocytes, the evolving of a "supramaximalecbolic-stimulation" process. The PP involvement as a modulating agent of pancreon's reactivity is reflected by the progressive increment of its plasma values in the first week of an evolving AP episode. In the AP associated to a large meal, an overpowering of the pancreon's brake might have a pivotal role. In experimental and clinical chronic alcoholism, a vagal neuropathy of the Pavlov inhibitory fibers that, as a consequence, impairs the pancreon's brake through a depression of PP secretion is at the basis of an enhanced reactivity of the duodeno-pancreatic reflexes. The latter leads to intrapancreatic cholinergic hypertonus and to Vater papilla's dysfunction. These changes, plus an enhanced pancreocyte's response to CCK, are at the core of acinar cell "supramaximal stimulation" with the organelle disruption that process implies. The intrapancreatic cholinergic hypertonus, the enhanced exocrine cell reactivity to CCK stimulation, and the augmented resistance to the pancreatic secretion flow at Oddi sphincter, explain the aggravating influence of chronic alcoholism on an episode of acute biliary pancreatitis. As the PP secretion, normally elicited by secretin, CCK, food and insulin hypoglycemia, is depressed in the presence of an augmented number of PP cells, as it is in the cases of chronic alcoholics, cystic fibrosis patients and, also, in dogs with pancreatic fibrosis (ductal ligation), it has been inferred, besides our postulated impairment of the Pavlov inhibitory fibers in the vagus nerves, that the defect of PP release is localized to the common final pathway of the above stimuli, probably in or near the PP cell itself This review was prompted by the unexpected experimental finding in canines that Tissucol-induced pancreatic ductal blockade elicits Pancreatic Polypeptide (PP) release and seems to be at the basis of the beneficial effects on taurocho- late-induced acute pancreatitis (AP). In the release mechanism of this regulatory peptide secreted by PP cells located in the periphery of Langerhans islets and scattered in the ductal epithelium, two neuroendocrine reflexes (NER) are involved. The "short" NER is evoked from the duodenum by an unknown component of bile-pancreatic secretion. The "long" NER is triggered by a vagovagal reflex. PP induces a depression of the intrapancreatic cholinergic tone. On the one hand suppressing, hormonally, nervous impulses discharge from the vagal nuclear complex in the brainstem. On the other, interfering paracrinically on the cholinergic transmission by acting, presynaptically, on post-ganglionic cholinergic neurons. The resulting PP-evoked fall of the intrapancreatic cholinergic tone depresses the hormone induced (secretin, CCK) pancreons secretory response. PP, with other agents, contributes to the "fail-safe" system or pancreon's brake that

Streptozotocin-induced diabetes, bile-pancreatic secretion and insulo-pancreon-axis interaction.

The present tests were undertaken in order to analyze in male Wistar rats the changes in the exocrine and endocrine pancreas and on the interactions that normally evolve in the insulo-pancreon-axis. To evaluate this by a single i.p. Boots secretin injection, glycemia (G), amylasemia (A) and lipasemia (L) were determined. In bile-pancreatic secretion, we analyzed, pre and post-secretin, the following parameters: volume (V), bicarbonate output (BO), amylase output (AO) and lipase output (LO). Three groups of tests were done: a) control (C); b) streptozotocin-treated non-diabetic-rats (St-ND) and c) streptozotocin-treated diabetic animals (St-D) which showed morning glycemia values higher than 16.0 mmol/l. Four months later, under Tiopental i.p anesthesia, a bile-pancreatic fistula was done. Following a 30 min basal period, Boots secretin (20 CU/kg) was i.p injected. Bile-pancreatic secretion put in evidence a significant fall of BO in both St-ND and St-D series. In controls, AO revealed a post-secretin increase of 160%, while in the St-D rats showed a depression of 41%. The behavior of L was different, being augmented (+27%) in the C, while in the St-D rats the response was significantly higher (+95%). In bile-pancreatic-secretion, the fall of BO and AO in the St-ND and St-D series in respect to the C, are probably consequence of the diminishing potentiating effects exerted normally by insulin on the secretin-induced water and bicarbonate secretion of the pancreon units. In contrast, the rising of LO in the St-D, an expression of an enhancing pancreocyte's synthesis and secretion of lipase. The blood changes of A (depression) and of L (increase) in respect to the C values, although without reaching significant level, mirror those observed in bile-pancreatic secretion.

[Biochemical profile of the pancreatic function: pancreolauril and oral glucose tolerance tests]. / Evaluación bioquímica de la función pancreática: Pruebas del pancreolauril y de la tolerancia a la glucosa oral.

BACKGROUND: The pancreas is a mixed gland that takes part in the digestion of nutrients and in the homeostasis ofglycemia. Chronic pancreopathy is the cause of secretory insufficiency, characterized by an inflammatory process that leads to fibrosis of the pancreas, with a progressive loss of both exocrine and endocrine functions of the gland. OBJECTIVE: To study both the exocrine and endocrine pancreatic relationship in patients with pancreatopathies and other non-pancreatic digestive alterations, by means of serum pancreolauril (sPL) and oral glucose tolerance tests (OGTT). Glycemia and insulin, basal and at 30, 60 and 120 minutes; amylase and lipase; and the HOMA index (homeostatic model) were determined in serum. MATERIAL AND METHODS: Thirty-two patients were evaluated: normal OGTT (n=11, control group) and pathologic OGTT (n=21). From the latter group, a subgroup (n=11) with a diagnosis of chronic pancreatitis (CP) was studied. RESULTS: Patients with pathologic OGTT in relation with normal OGTT presented a significant increase of glycemia at the four periods of time and of insulin at 120 minutes (P < 0.05), and a significant decrease of sPL (P < 0.05). In patients with CP, men were more than women, and all of them presented a pathologic OGTT and the sPL was significantly lower (P < 0.001). CONCLUSION: By the biochemical tests used, pancreas functionality corresponds with a close relationship between exocrine and endocrine pancreas. Thus, we suggest the use of the sPL test as a helpful tool for the diagnosis of CP.

Streptozotocin-induced diabetes, bile-pancreatic secretion and insulo-pancreon-axis interaction / Streptozotocin-induced diabetes, bile-pancreatic secretion and insulo-pancreon-axis interaction.

The present tests were undertaken in order to analyze in male Wistar rats the changes in the exocrine and endocrine pancreas and on the interactions that normally evolve in the insulo-pancreon-axis. To evaluate this by a single i.p. Boots secretin injection, glycemia (G), amylasemia (A) and lipasemia (L) were determined. In bile-pancreatic secretion, we analyzed, pre and post-secretin, the following parameters: volume (V), bicarbonate output (BO), amylase output (AO) and lipase output (LO). Three groups of tests were done: a) control (C); b) streptozotocin-treated non-diabetic-rats (St-ND) and c) streptozotocin-treated diabetic animals (St-D) which showed morning glycemia values higher than 16.0 mmol/l. Four months later, under Tiopental i.p anesthesia, a bile-pancreatic fistula was done. Following a 30 min basal period, Boots secretin (20 CU/kg) was i.p injected. Bile-pancreatic secretion put in evidence a significant fall of BO in both St-ND and St-D series. In controls, AO revealed a post-secretin increase of 160

, while in the St-D rats showed a depression of 41

. The behavior of L was different, being augmented (+27

) in the C, while in the St-D rats the response was significantly higher (+95

). In bile-pancreatic-secretion, the fall of BO and AO in the St-ND and St-D series in respect to the C, are probably consequence of the diminishing potentiating effects exerted normally by insulin on the secretin-induced water and bicarbonate secretion of the pancreon units. In contrast, the rising of LO in the St-D, an expression of an enhancing pancreocyte’s synthesis and secretion of lipase. The blood changes of A (depression) and of L (increase) in respect to the C values, although without reaching significant level, mirror those observed in bile-pancreatic secretion.

Pancreatitis y pancreatopatía crónica: evaluación fisiopatogénica, clínica y funcional: (basada en 1.300 casos en más de tres décadas en el Hospital de Clínicas de Bs. As.) / Chronic pancreatitis and chronic pancreatopathy: physiopathogenic, clinical and funcitonal evaluation. experience with 1,300 cases during three decades

Siguiendo a una experiencia de 33 años, de orden clínico y funcional (test de secretina), se intenta, por una parte, precisar los conceptos de pancreatitis crónica (PC) y de pancretopatía crónica (Pt.p.Cr.). Por otra, de consignar los índices de incidencia y de sus peculiaridades clínicas de expresión. El término de PC se propone cuando: "Las alteraciones estructurales del páncreas, con las eventuales modificaciones de los órganos y elementos anatómicos que con él se vinculan, y/o el déficit funcional de su componente exocrino ("pancreón") constituyen la fuente de la expresión clínica que predomina, de manera ostensible, en el complejo sindromático que exhibe el paciente en evaluación". Se estima como no ajustada a la realidad la noción clásica que considera a la PC como una afección de curso progresivo inexorable. Se enfatiza, por el contrario, la noción de que la PC cuando es adecuadamente tratada puede detener su evolución e, incluso, mostrar evidencias clínico-funcionales de su capacidad regenerativa. La denominación de pancreatopatía crónica (Pt.p.Cr.) es propuesta para aquellas condiciones en las que: "Los signos y/o síntomas originados por eventuales alteraciones anátomos-estructurales del páncreas y/o por modificaciones funcionales de su componenete secretorio exocrino se hallan disimuladamente inmersos dentro de un complejo sindromático que tiene génesis extra-pancreonal". De los 1.300 tests de secretina efectuados, 100 fueron dedicados a perfilar la respuesta secretoria exocrina normal. Y ello tanto en el hombre como en la mujer, discriminando, además, en ambos sexos, los resultados obtenidos por encima y por debajo de una edad crítica límite trazada a los 45 años. En 368 casos, la evaluación conjunta clínica-funcional permitió incluir a los pacientes dentro de la categoría de las PC. Dentro de esta entidad nosológica, se hizo el distingo entre la PC calcificante (alcohólica e idiopática), la autoinmune y la obstructiva. Como PC alchólica fueron.

Following a clinical evaluation and an exocrine pancreatic secretion exploration with the secretin test for more than three decades, we have tried to delineate the concepts of chronic pancreatitis (CP) and chronic pancreatopathy (Chr. Ptp). Besides, the rate of incidence of these two clinical entities in the Clinicas Hospital of Bs. As. was analyzed and discussed. The term CP was accepted when: "The anatomo-structural changes of the pancreatic gland and/or the exocrine functional component impairment constitute the patient's dominant clinical expresion". It is considered as erroneous and misleading the assumption that considers CP as a disease of an inexorable progressive course. On the contrary, the authors empehasize their conviction, based on experimental and clinical experiences, that CP is susceptible, when appropriately treated, of stopping its evolution and even disclose clinical-functional imporovements testifyng the inherent regenerative capacity of the gland. In contrast to the above, the denomination of Chr.Ptp. should be restricted when: "The signs and/or symptoms induced by the anatomo-structural changes of the pancretic gland and/or the functional derangement of the exocrine component remain disguised in the clinical syndrome of other diseases". Out of the 1,300 secretin tests performed, 100 were done on healthy controls. This study allowed establishing the normal statistical values of the different parameters. Besides, of showing the differences between men and women, especially above the critical age of 45. This clinical-functional evaluation allowed classifying 368 cases as CP. The folowing sub-groups were delineated: Calcifyiung "CP" (alcoholic, 240 cases and idiopathic, 119 cases); autoimmune CP (n=7) and Obstructive "CP" (n=11). In the Chr.Ptp. entity were classified 171 cases. As it is implied in the definition, this type of chronic inflammation of the pancreatic gland remained immersed in other disease entities.

Lipasa: una enzima singular por sus interacciones neuro-hormonales. (Revisión y análisis experimental y clínico) / Lipase: a particular enzyme because of its neuro-hormonal interactions

Un objetivo de esta presentación es el de analizar las peculiaridades distintivas de la enzima lipasa proveniente de diferentes fuentes: gástrica (LG), intestinal (LI)hepática (LH), lipoproteica (LLP), pero, en especial, aquella de la pancreática (LP), sobre todo en lo relativo a sus interacciones neuro-hormonales.