Simple approximation of sample size for precise estimates of SARS-CoV-2 infection from point-seroprevalence studies.

OBJECTIVE: This study aimed to model the precision of SARS-CoV-2 seroprevalence estimates. METHODS: Sample size and precision estimates were calculated using the normal approximation to the binomial distribution. The relationship between sample size and precision was visualized across a range of assumed SARS-CoV-2 seroprevalence from 2% to 75%. RESULTS: The calculation found that 2% precision was attainable by taking moderately sized sample sets when the expected seroprevalence of SARS-CoV-2 infection exceeds 2%. In populations with a low incidence of SARS-CoV-2 infection and an expected seroprevalence of less than 2%, larger samples are required for precise estimates. CONCLUSIONS: Taking a sample of 177-1000 participants can provide precise prevalence estimates of SARS-CoV-2 infection in vaccinated and unvaccinated populations. Larger sample sizes are only necessary in low prevalence settings.

Kyasanur Forest disease virus non-mouse animal models: a pilot study.

OBJECTIVES: Mouse models have delivered variable recapitulation of Kyasanur Forest disease (KFD) pathology and consistently demonstrated neurological involvement which may be a limited feature of human disease. With the purpose of more accurately modelling human disease progression we infected several small-mammalian models: guinea pigs, hamsters and ferrets with a titered infectious dose of Kyasanur Forest disease virus (KFDV). Clinical indicators of disease severity were observed for seventeen days, on day eighteen a visual post-mortem analysis of visceral organs was conducted. Viral load in selected tissues was measured to infer disease signs and the establishment of viral replication. DATA DESCRIPTION: Daily monitoring did not reveal any observable signs of illness; weight loss was minimal across species and gross pathology did not indicate severe viral infection. Tissue specific tropism and establishment of viral infection was monitored by quantitative real-time polymerase chain reaction (qRT-PCR). No viral replication was detected in ferrets (n = 0/3), but was present in the spleen of guinea pigs (n = 3/3) and the brain of hamsters (n = 3/3). Low levels of viral RNA were detected in multiple hamster tissues (kidney, liver, lung and spleen) suggesting the possibility of viral tropism and possible adaptation to the host. No serological tests were performed.

Pro-cognitive activity in rats of 3-furan-2-yl-N-p-tolyl-acrylamide, a positive allosteric modulator of the α7 nicotinic acetylcholine receptor.

BACKGROUND AND PURPOSE: α7 nicotinic acetylcholine receptors (α7 nAChRs) may represent useful targets for cognitive improvement. The aim of this study is to compare the pro-cognitive activity of selective α7-nAChR ligands, including the partial agonists, DMXBA and A-582941, as well as the positive allosteric modulator, 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2). EXPERIMENTAL APPROACH: The attentional set-shifting task (ASST) and the novel object recognition task (NORT) in rats, were used to evaluate the pro-cognitive activity of each ligand [i.e., PAM-2 (0.5, 1.0, and 2.0 mg·kg(-1) ), DMXBA and A-582941 (0.3 and 1.0 mg·kg(-1) )], in the absence and presence of methyllycaconitine (MLA), a selective competitive antagonist. To determine potential drug interactions, an inactive dose of PAM-2 (0.5 mg·kg(-1) ) was co-injected with inactive doses of either agonist - DMXBA: 0.1 (NORT); 0.3 mg·kg(-1) (ASST) or A-582941: 0.1 mg·kg(-1) . KEY RESULTS: PAM-2, DMXBA, and A-582941 improved cognition in a MLA-dependent manner, indicating that the observed activities are mediated by α7 nAChRs. Interestingly, the co-injection of inactive doses of PAM-2 and DMXBA or A-582941 also improved cognition, suggesting drug interactions. Moreover, PAM-2 reversed the scopolamine-induced NORT deficit. The electrophysiological results also support the view that PAM-2 potentiates the α7 nAChR currents elicited by a fixed concentration (3 µM) of DMXBA with apparent EC50 = 34 ± 3 µM and Emax = 225 ± 5 %. CONCLUSIONS AND IMPLICATIONS: Our results support the view that α7 nAChRs are involved in cognition processes and that PAM-2 is a novel promising candidate for the treatment of cognitive disorders.

Analgesic and sedative activities of lactucin and some lactucin-like guaianolides in mice.

Lactucin (1) and its derivatives lactucopicrin (2) and 11beta,13-dihydrolactucin (3), which are characteristic bitter sesquiterpene lactones of Lactuca virosa and Cichorium intybus, were evaluated for analgesic and sedative properties in mice. The compounds showed analgesic effects at doses of 15 and 30 mg/kg in the hot plate test similar to that of ibuprofen, used as a standard drug, at a dose of 30 mg/kg. The analgesic activities of the compounds at a dose of 30 mg/kg in the tail-flick test were comparable to that of ibuprofen given at a dose of 60 mg/kg. Lactucopicrin appeared to be the most potent analgetic of the three tested compounds. Lactucin and lactucopicrin, but not 11beta,13-dihydrolactucin, also showed sedative properties in the spontaneous locomotor activity test.

Exogenous and endogenous ghrelin in gastroprotection against stress-induced gastric damage.

Ghrelin, identified in the gastric mucosa has been involved in control of food intake and growth hormone (GH) release but little is known about its influence on gastric secretion and mucosal integrity. The effects of ghrelin on gastric secretion, plasma gastrin and gastric lesions induced in rats by 75% ethanol or 3.5 h of water immersion and restraint stress (WRS) were determined. Exogenous ghrelin (5, 10, 20, 40 and 80 microg/kg i.p.) increased gastric acid secretion and attenuated gastric lesions induced by ethanol and WRS and this was accompanied by the significant rise in plasma ghrelin level, gastric mucosal blood flow (GBF) and luminal NO concentrations. Ghrelin-induced protection was abolished by vagotomy and attenuated by suppression of COX, deactivation of afferent nerves with neurotoxic dose of capsaicin or CGRP(8-37) and by inhibition of NOS with L-NNA but not influenced by medullectomy and administration of 6-hydroxydopamine. We conclude that ghrelin exerts a potent protective action on the stomach of rats exposed to ethanol and WRS, and these effects depend upon vagal activity, sensory nerves and hyperemia mediated by NOS-NO and COX-PG systems.

Ghrelin-a new gastroprotective factor in gastric mucosa.

Ghrelin, a novel peptide expressed in the gastrointestinal tract, especially in the gastric mucosa, exerts several biological activities including the stimulation of appetite and food intake, the stimulation of intestinal motility and the release of growth hormone. The aim of this study was to examine the expression of ghrelin in gastric mucosa after its exposure to ethanol and its effects on gastric lesions induced by ethanol with and without pretreatment with indomethacin. Acute gastric lesions were induced by intragastric administration of 75% ethanol in rats pretreated with saline-vehicle or ghrelin injected intraperitoneally (i.p.) without or with i.p. pretreatment with indomethacin. At the end of experiments, the rats were anesthetized, the stomach was exposed to measure gastric blood flow (GBF), to determine the area of gastric lesions and to take biopsy samples from the oxyntic mucosa for determination of transcripts of ghrelin, tumor necrosis alpha (TNF-alpha) and transforming growth factor alpha (TGFalpha) using RT-PCR and to assess the generation of PGE(2) by RIA. Exposure of gastric mucosa to 75% ethanol resulted in numerous mucosal lesions of an area of about 115 mm(2) and in the increase of mucosal expression of TNF-alpha, PGE(2), TGFalpha and ghrelin with concomitant decrease in GBF. Exogenous ghrelin reduced dose-dependently acute gastric lesions with simultaneous attenuation of GBF and a decrease in the expression of TNF-alpha but not TGFalpha. Pretreatment with indometahcin, which suppressed the generation of PGE(2) by about 85%, augmented ethanol-induced gastric lesions and eliminated the ghrelin-induced protection of mucosa against ethanol. We conclude that ghrelin, whose mucosal expression is enhanced after exposure to ethanol, exhibits a strong gastroprotection, at least in part, due to its anti-inflammatory action mediated by prostaglandins.

Biochemical and morphological study on liver Golgi complex in streptozotocin-diabetic and control rats treated with bis(kojato)oxovanadium(IV) [VO(ka)2]x2H2O. Part I. One week treatment with vanadium compound.

In comparison with untreated control, reduced body and liver weights were found in two groups of rats (such as control and STZ-diabetic) treated orally with bis(kojato)oxovanadium(IV) solution. Free blood sugar in STZ-diabetic rats was lower by about 38%, but did not achieve euglycemic values. Yields of Golgi-rich fraction were lower than those in untreated controls, similar to the activity of galactosyl transferase (GalT) in both vanadium treated groups (control and diabetic). Under electron microscope in the control kojate-treated group, subcellular changes were observed. The morphology of Golgi apparatus was typical, resembled that in untreated animals. In diabetic animals treated with kojate subcellular changes were less severe. Golgi apparatus was usually semicircular or arched in shape similar to that observed previously in diabetic untreated rats.