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Currently, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) has been reported in almost all countries globally, and no effective therapy has been documented for COVID-19 and the role of convalescent plasma therapy is unknown. In current study, 6 COVID-19 subjects with respiratory failure received convalescent plasma at a median of 21.5 days after first detection of viral shedding, all tested negative for SARS-CoV-2 RNA by 3 days after infusion, and 5 died eventually. In conclusion, convalescent plasma treatment can discontinue SARS-CoV-2 shedding but cannot reduce mortality in critically end-stage COVID-19 patients, and treatment should be initiated earlier.

Gastric acid plays an important role in digesting food (especially proteins), iron absorption, and destroying swallowed micro-organism. N4 is secreted by the oxyntic parietal cells. Its secretion is regulated by endocrine, neurocrine and paracrine mechanisms. Gastrin released from the antral G cell is the principal physiological stimulus of gastric acid secretion. The ECL cell is accepted as the source of histamine participating in the regulation o f acid secretion and is functionally and trophically controlled by gastrin. Amidated gastrin is the main biologically active form of gastrin, and its main precursor Gly-G-17 was formerly thought to be without any biological activity. However, recent studies raised the possibility of both secretory and trophic effects of Gly-gastrin. No Glt-G-17 receptor has been cloned yet. In paper I, the effect of this peptide on gastric acid secretion was examined in the totally isolated vascularly perfused rat stomach. This study clearly demonstrates that the administration of Gly-G-17 in high doses was followed by an increase in histamine release and gastric acid output. Moreover, Gly-G-17 induced gastric acid secretion was completely inhibited by the H2 receptor antagonist ranitidine. Thus, the natural interpretation of these data is that Gly-G-17 is a weak gastrin agonist, interacting with the CCK-2 receptor on the ECL cell, resulting in a subsequent release of histamine, which in turn stimulates the parietal cell. The stomach is also regulated by nerves, principally by the vagal nerves. The gastric neurons contain various neuropeptides, some of them, such ad PACAP are known to influence gastric acid secretion. In paper II, PACAP was studied with respect to the effect on gastric acid secretion using totally isolated vascularly perfused rat stomachs, chronic fistula rats and isolated parietal cells. The results show that its stimulatory effects on gastric acid secretion is mainly due to an increase in histamine release from the ECL cell. PACAP is a powerful stimulator of histamine release from the ECL cell. As mentioned above, aside from its stimulatory effect on gastric acid secretion, gastrin also has a trophic effect on the oxyntic mucosa, especially on the ECL cell. A definite connection has been found between hypergastrinemia and gastric carcinoids both in rats and humans. Moreover, some of the gastric adenocarcinomas in rodents with hypergastrinemia have been reclassified as ECLomas. However, spontaneous gastric ECL omas in laboratory animals are extremely rare. Japanese cotton rats (Sigmodon hispidus) have a very high incidence of gastric carcinomas occurring predominately in females, and which we previously showed, were associated with achlorhydria and hypergastrinemia. In paper III, the gastric carcinomas in cotton rats are described further. Particularly the oxyntic mucosa outside the tumour is shown to contain normal parietal cells indicating a normal ability to produce acid. Long-term potent inhibitors of acid secretion resulting in secondary hypergastrinemia will induce ECL cell hyperplasia and probably carcinoids. Accordingly, the induction of ECL-cell hyperplasia and carcinoids remains a topic of considerable concern, especially in young individuals. Furthermore, the stomach is important for the absorption of calcium. Achlorhydria has been described as causing impairment of calcium absorption. Thus, a mechanism related to gastric acid secretion has been postulated to be involved in osteopenia developing in patients after gastric resection. More specifically, a postulated peptide, gastrocalcin, has been hypothesised to exist in the ECL cell. We therefore examined the effect of long-term hypergastrinemia secondary to drug induced hypoacidity with respect to bone developing in young male rats (paper IV). Long-term potent acid inhibition evoked a marked increase in plasma gastrin levels, leading to enlargement of oxyntic mucosa with ECL cell hyperplasia. However, body weight and bone mineral density were reduced in the hypergastrinemic young male rats. These findings do not support the hypothesis that the ECL cell plays a role in bone metabolism. Finally, anaesthetized animal models have been widely used to study gastric acid secretion. However, anaesthetic agents also affect acid output. Anaesthetic agents naturally reduce acid secretion by interaction with neural activity, but could also play a role by affecting the function of the different cells taking part in the regulatory chain of acid secretion as well as the parietal cell itself. In paper V, the totally isolated vascularly perfused rat stomach was used to study the effect of anaesthetic agents on the ECL cell and the parietal cell functions. The results indicate that anaesthetic agents can also affect gastric acid secretion through a direct inhibitory action on parietal cells and ECL cells. dr.med. dr.med.

To evaluate the clinical significance of endocrine-like tumor cells in human colorectal carcinomas.The immunohistochemistry method (ABC) using a rabbit polyclonal antibody against human chromogranin A (CGA) was employed to determine changes in endocrine-like tumor cells from the surgically resected colorectal carcinoma tissues of patients (35 males and 27 females, aged from 19 to 78 years, with a mean age of 50.3 years). Of the 62 specimens, 44 were from rectal carcinomas, 18 from colonic carcinomas, 14 from lymph nodes and 48 from non-involvement. Dukes classification revealed 19 of the cases were in stage A, 29 cases were in stage B and 14 cases were in stage C. All of the specimens were fixed with 10% formalin, embedded with paraffin and cut into 5 μm sections. Additionally, the correlations among CGA-positive tumor cells, as well as the clinicopathologic data, age and sex of the patients, were also investigated.CGA-positive tumor cells were found in 35.5% of the patients with colorectal cancers, representing 20.0% (5 of 25) and 45.9% (17 of 37) of the aged and non-aged, respectively. These differences were significant (χ(2) test, P0.05). Nevertheless, no significant correlations were found between the CGA-positive tumor cells and the sex, Dukes stages, tumor location, degree of histological differentiation or presence of lymph node metastasis.The low incidence of endocrine-like tumor cells found in the aged patients may be a new pathological feature for colorectal carcinomas, which could explain why the aged patients usually had a better prognosis. The exact significance of these findings requires further characterization.