The vagal nerve as a link between the nervous and immune system in the instance of polymicrobial sepsis

Background The role of the vagal nerve in the autonomic nervous system is widely well known. Recently, an additional function was revealed serving as a connector between the nervous and immune system. This connection is called the “cholinergic inflammatory pathway.” Through stimulation of the acetylcholine receptors located upon the macrophages, the “unspecific” immune system can be directly influenced. Methods The vagal nerve was completely transected directly posterior to its passage through the diaphragm. The effect of complete vagotomy was analyzed using a murine model of polymicrobial peritonitis (colon ascendens stent peritonitis, CASP). Survival and clinical course of vagotomized or sham-operated mice were analyzed in the CASP model. Results After CASP surgery, vagotomy led to a significantly increased mortality (64.7%) in comparison to sham-vagotomized animals (34%). No difference in the bacterial load of various tissues (lung, liver, spleen, blood, lavage fluid, and kidney) from septic animals with or without vagotomy was observed. Vagotomized animals reveal elevated serum cytokine levels (TNF, IL-6, IL-10, and MCP-1) 20 h after the induction of polymicrobial peritonitis. Conclusion The vagal nerve is therefore an important modulator of the immune system. W. Kessler and T. Traeger contributed equally to this work Best of Forum Papers presented at the Annual Meeting of the German Society of Surgery, 2–5 May 2006, Berlin, Germany     

Increased prevalence of apolipoprotein E2 in patients with retinitis pigmentosa

Apolipoprotein E isoforms were determined in 139 unrelated patients with retinitis pigmentosa (RP). When compared to prevalence rates for the general population in Germany, an increased prevalence was observed for phenotypes E2/E2: 10.1 vs. 1.0% (p less than 0.001), E2/E3: 19.4 vs. 12.0% (p less than 0.05), and E2/E4: 5.8 vs. 1.5% (n.s.), while the prevalence appeared to be reduced for phenotypes E3/E3: 48.9 vs. 59.8% (n.s.) E3/E4: 13.7 vs. 22.9% (p less than 0.05), and E4/E4: 2.2 vs. 2.8% (n.s.). These findings suggest that genetically determined abnormalities of plasma lipoprotein metabolism may be associated with some forms of RP.     

Basophil releasability in severely burned patients.

Thermal injury is known to induce dysregulation of the immune system; however, the precise mechanisms have to be clarified. We investigated the histamine release of basophil granulocytes from severely burned patients (n = 12) after stimulation with anti-IgE or the Ca-ionophore A 23187, respectively. The anti-IgE-induced basophil histamine release of all patients was reduced in comparison to healthy donors beginning at day one postburn (p.b.) (5.0 +/- 2.3% vs. 30.5 +/-3.4%), while the Ca-ionophore-induced release was not decreased before day two p.b. Basophils of patients who finally succumbed to their injuries showed poor responsiveness (to zero levels) over the total time. In contrast, the basophil releasability of surviving patients returned to nearly normal levels (fifth to seventh week p.b.). Already in the second week p.b. there was a significant difference in histamine release between survivors and nonsurvivors [e.g., days 6-9 p.b.: 23.7 +/- 4.0 vs. 6.9 +/- 2.7 (p less than 0.005) after Ca-ionophore stimulation]. The altered basophil histamine release was neither due to a diminished dose- or a delayed time-response to the stimuli nor due to differences in the basophil counts or the cellular histamine content. Our data indicate that the decrease of the basophil releasability, which may be secondary to altered signal transduction pathways in severely burned patients correlates with the clinical outcome.     

Management und Kontrolle einer Influenzapandemie Konzeptionelle Überlegungen für einen deutschen Influenzapandemieplan

The World Health Organization (WHO) and the majority of the influenza experts assume that an influenza pandemic might reemerge again at any time. Therefore WHO has called upon all member states to set up a national pandemic preparedness plan. For Germany such a plan is long overdue. In order to gain as much time as possible early identification of the pandemic virus is of highest priority. Furthermore progression of a pandemic is influenced by the time needed to develop a subtype specific vaccine as well as by the vaccines availability. However, in case of a pandemic a shortage of vaccines and prophylactic pharmaceuticals cannot be avoided. Therefore, decisions have to be made in order to establish priorities concerning the vaccination and the prophylactic and/or therapeutic antimicrobial treatment of selected sub-populations. There is also a need to lay down measures ensuring the distribution of vaccines and antiviral drugs, adequate health care and ambulance service, and the organization of dignified funerals of the deceased. It is also necessary to enter into an early agreement with vaccine manufacturers on a guaranteed supply of respective batches of vaccine doses. In addition procedures should be established to allow an increase in vaccine production in case of a pandemic. There is also a need for early agreements with the manufacturers of antiviral agents and for a decision concerning the establishment of a national stockpile to guarantee an adequate supply. Some measures must already be taken in the inter-pandemic period. Those are: enhancement of surveillance and research, development of new vaccines and new methods of vaccine production, licensing of new vaccines in case of a pandemic and establishment of a national influenza committee. Problems like the effectiveness of antiepidemic measures, such as immigration control and the closing of schools, must be solved in advance of a pandemic.     

Postnatal formation of the blood-testis barrier in the rat with special reference to the initiation of meiosis

Summary Postnatal formation of the Blood-Testis Barrier (BTB) in the rat was studied by either fixation in hypertonic fixative or employing lanthanum tracer. After 15 days of age, meiosis has reached different stages of spermatogenesis in differnt zones of the seminiferous cords. Only in those parts where germ cells are in the pachytene stage of meiosis do Sertoli cells form an effective barrier or tight compartment. Between 16 and 19 days of age, final formation of the BTB, which is to be found in the adult rat testis, occurs by zygotene and then leptotene stages successively entering the tight compartment. Thus, formation of a BTB by Sertoli cells does not occur synchronously along the length of the seminiferous cord but in accordance with the stage of meiosis of the associated germ cells.     

Prefrontal cortex dysfunction and depression in atypical parkinsonian syndromes.

Depressive symptoms are common in patients with neurodegenerative disorders. Imaging studies suggest that a disruption of frontal-subcortical pathways may underlie depression associated with basal ganglia disease. This pilot study tested the hypothesis that frontal dysfunction contributes to depression associated with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Depressed patients with MSA (n = 11), PSP (n = 9), and age-matched controls (n = 25) underwent measures of cerebral glucose metabolism applying positron emission tomography with (18)F-fluorodeoxyglucose. Regional metabolism in the patient groups was compared to the normal subjects using the voxel-based statistical parametric mapping. Depressive symptom severity (Hamilton Depression Rating) and degree of locomotor disability (Hoehn & Yahr) were assessed in the patient groups. The association between prefrontal metabolism and the occurrence of depressive symptoms and the degree of locomotor disability was investigated. When compared to controls, MSA patients revealed significant metabolic decreases in bilateral frontal, parietal, and cerebellar cortex and in the left putamen. In PSP patients, significant hypometabolism was demonstrated in bilateral frontal cortex, right thalamus, and midbrain. Depression severity but not the patients' functional condition was significantly associated with dorsolateral prefrontal glucose metabolism in both patient groups. The findings of this pilot study support the hypothesis that depressive symptoms in MSA and PSP are associated with prefrontal dysfunction.