The expression of both constitutive and inducible forms of nitric oxide synthase (NOS) was investigated by immunohistochemical staining of formalin-fixed paraffin-embedded sections in normal and Listeria monocytogenes-infected brains of goats. In normal control goats, a small number of neurons showed immunoreactivity of both iNOS and nNOS, and the number of iNOS-positive neurons was higher than the number of nNOS-positive neurons. In natural listeriosis, listeria antigens were easily immunostained in the inflammatory cells of microabscesses. In this lesion, the immunoreactivity of iNOS in neurons was more intense than the control, but nNOS was not. In microabscesses, nNOS was weakly visualized in macrophages and neutrophils, while iNOS was expressed in macrophages, but not in neutrophils. These findings suggest that normal caprine brain cells, including neurons, constitutively express iNOS and nNOS, and the expressions of these molecules is increased in Listeria monocytogenes infections. Furthermore, inflammatory cells, including macrophages, expressing both nNOS and iNOS may play important roles in the pathogenesis of bacterial meningoencephalitis in goat.
Animals ; Brain/cytology/*enzymology ; Glial Fibrillary Acidic Protein/analysis ; Goat Diseases/*enzymology ; Goats ; Immunohistochemistry ; Listeria Infections/enzymology/*veterinary ; Neurons/*enzymology ; Nitric Oxide Synthase/*analysis ; Nitric Oxide Synthase Type I ; Nitric Oxide Synthase Type II

Although heparin is better known as an anticoagulant, it also has several anti-inflammatory effects. Heparin is known to inhibit neutrophil adhesion, chemotaxis and oxygen free radical production. In addition, heparin is also known to act as an oxygen radical scavenger. Our hypothesis was that heparin would attenuate renal ischemia reperfusion injury. In this study, we investigated whether heparin had a protective effect on renal ischemia reperfusion injury. Sheep (n = 12) were prepared for the chronic study with venous, arterial and urinary catheters inserted. In addition, pneumatic occluders and ultrasonic flow probes were placed on renal arteries. After a 5-day recovery period, the sheep were randomized to either a heparin treatment group (400 IU/kg i.v. bolus 10 minutes before renal artery occlusion, followed by a continuous effusion 25,000 IU in 250 ml of 0.9% NaCl at 10 ml/hr, n = 6) or a control group (n = 6), which received an equivalent volume of 0.9% NaCl. All the sheep then underwent 90 minutes of bilateral renal ischemia followed by 24 hours of reperfusion. Blood urea nitrogen (BUN), serum creatinine (Scr), and creatinine clearance (CrCl) were determined at various intervals during both the ischemic and reperfusion periods. Kidney tissue samples were obtained at autopsy for histologic examination. As a result, there were significant differences in the degree of inflammation (1.50 +/- 1.24 Vs 0.50 +/- 0.79, P < 0.05) between the control and heparin treatment groups, but not in the degree of injury (2.83 +/- 0.44 Vs 2.33 +/- 0.28). In this study, heparin significantly attenuated polymorphonuclear leukocytes (PMNs) infiltration within the interstitium, but it did not affect the degree of renal damage as measured by urinary chemistries or renal tubular damage as assessed by histopathologic evaluation.
Animal ; Anticoagulants/pharmacology* ; Cell Movement/drug effects ; Female ; Heparin/pharmacology* ; Ischemia/pathology* ; Kidney/pathology ; Kidney/drug effects* ; Neutrophils/physiology ; Neutrophils/drug effects* ; Renal Circulation* ; Reperfusion Injury/pathology* ; Sheep

Western-style diets (WD) are associated with greater risk of colon cancer. Exposure to 2-amino-1-methyl-6-phenylimidazo(4,5-b) pyridine (PhIP), a food-borne carcinogen, is linked to increased colon cancer risk. In contrast, intake of apiaceous and cruciferous vegetables (APIs and CRUs) is associated with reduced risk. Here we evaluated effects of a WD alone or a WD containing API or CRU, relative to a purified diet (basal), on colon cancer risk in mice. All diets were fed at one of two concentrations of PhIP (100 or 400 ppm). The activity of the hepatic PhIP-activating enzyme, cytochrome P450 (CYP) 1A2, was examined at week 4 and colonic precancerous lesions (aberrant crypt foci, ACF) were enumerated at week 12. In low PhIP-fed groups, CYP1A2 activity was greater for CRU than all other groups, which did not differ from one another. WD had a significantly greater effect on the formation of ACF than the basal diet. In groups fed API or CRU, the ACF number was reduced to the level observed in the basal diet-fed group. In high PhIP-fed groups, all WD-based diets had greater CYP1A2 activity than the basal diet-fed group. Surprisingly, the basal diet group had more ACF than the WD group, and API and CRU groups did not differ from the WD alone group. Thus, at the lower dose of PhIP, the WD increased colon cancer risk in mice, compared to a purified diet, and APIs and CRUs reduced the risk of the WD. However, at the higher dose of PhIP, the enhancement of colon cancer risk by the WD was not evident, nor was the chemopreventive effect of these vegetables.

Purpose: Medical schools have faced various challenges in preparing their clinical students for the frontlines of a pandemic. This study investigated medical students’ satisfaction with their institutions during the coronavirus disease 2019 (COVID-19) pandemic with the intention of guiding educators in future public health crises. Methods: In this cross-sectional study surveying students in clinical rotations, the primary outcome was overall satisfaction regarding medical schools’ responses to the pandemic, and the four secondary outcomes were school communication, exposure to COVID-19, availability of personal protective equipment, and access to COVID-19 testing. Results: The survey was distributed to ten medical schools, of which 430 students responded for a response rate of 13.0%. While most students were satisfied (61.9%, n=266) with their schools’ response, more than one in five (21.9%, n=94) were dissatisfied. Among the four secondary outcomes, communication with students was most predictive of overall satisfaction. Conclusion In future crises, schools can best improve student satisfaction by prioritizing timely communication.

Background/Aims: Depression and anxiety are associated with poorer outcomes in patients with hepatocellular carcinoma (HCC). However, the prevalence of depression and anxiety in HCC are unclear. We aimed to establish the prevalence of depression and anxiety in patients with HCC. Methods: MEDLINE and Embase were searched and original articles reporting prevalence of anxiety or depression in patients with HCC were included. A generalized linear mixed model with Clopper-Pearson intervals was used to obtain the pooled prevalence of depression and anxiety in patients with HCC. Risk factors were analyzed via a fractional-logistic regression model. Results: Seventeen articles involving 64,247 patients with HCC were included. The pooled prevalence of depression and anxiety in patients with HCC was 24.04% (95% confidence interval [CI], 13.99–38.11%) and 22.20% (95% CI, 10.07–42.09%) respectively. Subgroup analysis determined that the prevalence of depression was lowest in studies where depression was diagnosed via clinician-administered scales (16.07%;95% CI, 4.42–44.20%) and highest in self-reported scales (30.03%; 95% CI, 17.19–47.01%). Depression in patients with HCC was lowest in the Americas (16.44%; 95% CI, 6.37–36.27%) and highest in South-East Asia (66.67%; 95% CI, 56.68–75.35%). Alcohol consumption, cirrhosis, and college education significantly increased risk of depression in patients with HCC. Conclusions One in four patients with HCC have depression, while one in five have anxiety. Further studies are required to validate these findings, as seen from the wide CIs in certain subgroup analyses. Screening strategies for depression and anxiety should also be developed for patients with HCC.