Aging, aluminium and basal forebrain lesions modify substrate kinetics of erythrocyte membrane Na,K-ATPase in the rat

Several studies suggested that the activity of erythrocyte Na,K-ATPase declines with aging. Here, it is postulated that alterations in the substrate kinetics of the erythrocyte membrane Na,K-ATPase could be more aggravated in conditions of brain cholinergic dysfunction seen in Alzheimer's disease than in normal aging. To test this hypothesis, we compared the Na,K-ATPase activity (Vmax/Km parameters) in aged rats with those in young rats with brain cholinergic dysfunction induced by electrolytic-, kainic acid-lesioned nucleus basalis magnocellularis (NBM) or by intracerebroventricular AlCl_{3} administration. In the above mentioned groups, Vmax values were significantly lower in comparison to the control animals. Furthermore, Km values were significantly higher in animals with electrolytic-induced NBM lesions, AlCl_{3} treated rats and aged animals. However, Km was significantly lower in kainic acid-induced NBM lesions compared to the control group. The Na,K-ATPase catalytic efficiency, estimated by the ratio Vm/Km, decreased as followed: young animals > aged animals > kainic acid lesion > electrolityc lesion > AlCl_{3}. Our data suggest that neurodegenerative processes similar to those seen in Alzheimer's disease affect the sodium/potassium pump functionality which might be detected in peripheral blood erythrocyte membranes.     

Histamine and histamine intolerance

Histamine intolerance results from a disequilibrium of accumulated histamine and the capacity for histamine degradation. Histamine is a biogenic amine that occurs to various degrees in many foods. In healthy persons, dietary histamine can be rapidly detoxified by amine oxidases, whereas persons with low amine oxidase activity are at risk of histamine toxicity. Diamine oxidase (DAO) is the main enzyme for the metabolism of ingested histamine. It has been proposed that DAO, when functioning as a secretory protein, may be responsible for scavenging extracellular histamine after mediator release. Conversely, histamine N-methyltransferase, the other important enzyme inactivating histamine, is a cytosolic protein that can convert histamine only in the intracellular space of cells. An impaired histamine degradation based on reduced DAO activity and the resulting histamine excess may cause numerous symptoms mimicking an allergic reaction. The ingestion of histamine-rich food or of alcohol or drugs that release histamine or block DAO may provoke diarrhea, headache, rhinoconjunctival symptoms, asthma, hypotension, arrhythmia, urticaria, pruritus, flushing, and other conditions in patients with histamine intolerance. Symptoms can be reduced by a histamine-free diet or be eliminated by antihistamines. However, because of the multifaceted nature of the symptoms, the existence of histamine intolerance has been underestimated, and further studies based on double-blind, placebo-controlled provocations are needed. In patients in whom the abovementioned symptoms are triggered by the corresponding substances and who have a negative diagnosis of allergy or internal disorders, histamine intolerance should be considered as an underlying pathomechanism.     

Heterosubtypic cross‐protection induced by whole inactivated influenza virus vaccine in mice: influence of the route of vaccine administration

Background

Development of influenza vaccines capable of inducing broad protection against different virus subtypes is necessary given the ever‐changing viral genetic landscape. Previously, we showed that vaccination with whole inactivated virus (WIV) induces heterosubtypic protection against lethal virus infection in mice. Whole inactivated virus‐induced cross‐protection was found to be mediated primarily by flu‐specific CD8+ T cells.

Objectives

As it has been demonstrated that the route of vaccine administration strongly influences both the quantity and quality of vaccine‐induced immunity, in this study, we determined which route of WIV administration induces optimal heterosubtypic cross‐protection.

Methods

We compared the magnitude of the immune response and heterosubtypic protection against lethal A/PR/8/34 (H1N1) infection after subcutaneous (SC), intramuscular (IM), and intranasal (IN) vaccination with A/NIBRG‐14 (H5N1) WIV.

Results

Subcutaneous and IM administration was superior to IN administration of influenza WIV in terms of flu‐specific CD8+ T‐cell induction and protection of mice against lethal heterosubtypic challenge. Surprisingly, despite the very low flu‐specific CD8+ T‐cell responses detected in IN‐vaccinated mice, these animals were partially protected, most likely due to cross‐reactive IgA antibodies.

Conclusion

The results of this study show that the magnitude of WIV‐induced flu‐specific CD8+ T‐cell activity depends on the applied vaccination route. We conclude that parenteral administration of WIV vaccine, in particular IM injection, is superior to IN vaccine delivery for the induction of heterosubtypic cross‐protection and generally appears to elicit stronger immune responses than mucosal vaccination with WIV.     

Changes in cardiac innervation during maturation in long-term diabetes

Diabetic autonomic neuropathy being a common complication of diabetes mellitus (DM) is related to an increased risk of cardiovascular mortality. However, mechanisms underlying changes of innervation density in affected hearts remain insufficiently understood. Hence, the aim of this study was to describe quantitative changes of intra-myocardial nerve terminals in hearts of diabetic rats of various ages.     

Cryosurgery of focal lesions of the liver in patients requiring reoperation

Cryosurgery ++ (cryoresection and cryodestruction) was carried out in 21 of a group of 43 patients (48.8%) during resection and +re-resection of the liver in repeated operations. One patient died. It was found that cryodestruction combined with radical and palliative resections of the liver in reoperations improved the late-term results of the operation significantly. With the use of cryotechniques, blood loss is reduced and intraoperative dissemination of the tumour cells and alveococcus and recurrences in the postoperative period are prevented.     

Skin Homografts in Patients with Cancer of the Cervix

Skin homografts were applied to patients with cervical cancer. In 9% (10 of 110) of untreated patients, grafts survived for more than two weeks. The frequency of prolonged graft survival was increased by pelvic surgery or radiotherapy. It was highest, 62% (34 of 55), in those with recurrent cancer. Recurrence and death in patients studied prior to treatment and followed up six months to two and a half years was three times more frequent in those with grafts tolerated over two weeks than in those rejecting them in a shorter period, i.e. five of 10 and 10 of 74, respectively.     

Value of using dietary factors in the prevention and treatment of ischemic heart disease

Influence of differentiated use of the alimentary factors on the lipemia level, hemocoagulation activity, arterial pressure level, carbohydrate tolerance and catecholamine content in the blood plasma of CHD patients was shown under the conditions of controlled dietotherapy. Incorporation of diet in multimodality therapy and prevention of this disease under inpatient, sanatorium-prophylactic and outpatient conditions was emphasized.