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     

Buffering the stomach content enhances the absorption of diflunisal in man

Diflunisal, a lipophilic salicylate, is absorbed more slowly in healthy volunteers than aspirin. In this paper we report on attempts to influence diflunisal absorption by buffering the gastric milieu. Sodium bicarbonate given together and 30 min after diflunisal tablets significantly (p less than 0.05) shortened the time to reach peak plasma concentration (tmax greater than 15 per cent), raised maximum plasma concentration slightly (Cmax 6 per cent) and increased the area under the plasma concentration-time curve (AUC greater than 8 per cent). Other pharmacokinetic parameters, including terminal half-life and renal elimination of the compound, were not considerably influenced. These findings indicate that the absorption of diflunisal was enhanced by increased gastric pH, presumably a result of an increased solubility of diflunisal in the stomach together with faster transport into the small intestine. In one volunteer, after intravenous administration diflunisal plasma concentrations declined in a triphasic manner with a terminal half-life of 12.8 h. The volume of distribution was approximately 10 per cent of body weight. Based on the ratio of AUC after equivalent i.v. and oral diflunisal doses, the absolute bioavailability was 89.5 per cent.     

The course of schizophrenia: Some remarks on a yet unsolved problem of retrospective data collection

Summary The retrospective assessment of symptoms and syndromes is a basic measure in research of the longitudinal course of schizophrenia. In spite of its importance there have been few studies evaluating the standard of quality of instruments for retrospective data collection. Combining retrospectively and cross-sectionally collected data on schizophrenic symptomatology in a cohort study over a period of 5 years revealed a significant underestimation of symptoms when assessed in retrospect. The need for studies on the validity of instruments for the retrospective assessment of symptoms is stressed.     

123I-amphetamine-SPECT in classical migraine and migraine accompagnée

Migraine is considered to be a functional neurological disorder. In classical migraine (headache associated with prodromal visual field disturbances) and migraine accompagnée (headache associated with transient neurological symptoms), disturbances of cerebral blood flow and amine metabolism are thought to be pathogenetic factors. However, conventional methods of neuroimaging (CAT, NMR) usually do not yield any pathological findings in patients. Since 123I-iodoamphetamine (123I-IMP) crosses the intact blood brain barrier, 123I-IMP-SPECT is used for the assessment of cerebral perfusion in various neurological diseases, including functional disorders. 123I-IMP-SPECT was performed on 5 patients with classical migraine and 18 patients with migraine accompagnée. At the time of investigation, all patients were symptom-free. Cerebral blood flow was decreased in all patients with migraine accompagnée, and often corresponded to the site of headache as well as to the topography of transient neurological symptoms. This reduction was most obvious in a patient with persisting neurological symptoms. Most patients with classical migraine, however, did not show any alteration of cerebral perfusion. It appears that migraine--and in particular migraine accompagnée--is characterized by a permanent alteration not only of cerebral blood flow but also of neuronal activity. Migraine attacks may occur in connection with exacerbations of preexisting metabolic alterations.     

Functional parameters before and after parathyroidectomy: a prospective, randomized long-term trial on different rat strains.

For clinical controls before and after parathyroidectomy and for evaluation of the function of transplants of parathyroid tissue, it is necessary to establish standard values of relevant laboratory parameters for donor and recipient animals as well as for different types of nutrition. Since no such data are yet available, it was the purpose to define such standards. In a prospective randomized trial on 400 rats of the Dark Agouti (DA) and Lewis strain, different functional laboratory parameters such as total calcium, intact parathyroid hormone, phosphate, 1.25-dihydroxyvitamin D, and alkaline phosphatase were measured under a standard and low calcium diet over a period of 40 weeks. Two hundred of these animals underwent a parathyroidectomy four weeks after the beginning of the study and specimens were evaluated histologically. For all eight different study groups normal values could be defined within tight limits for parameters which describe the function of the parathyroid gland or elements of calcium metabolism under different conditions. The optimal conditions for a transplantation model of parathyroid glands were established. Lewis-rats were identified as the ideal donor and DA rats as the better recipient animals. These data can serve as reference values for future studies on transplantation of the parathyroid without immunosuppression.     

Differential Stripping: Determination of the Amount of Topically Applied Substances Penetrated into the Hair Follicles

The determination of penetration pathways of topically applied substances into the skin is the subject of several investigations. Recently, follicular penetration has become a major focus of interest. To date, a direct, non-invasive quantification of the amount of topically applied substance penetrated into the follicles had not been possible. The development of such a method was the aim of this study. Therefore, the advantages of both stripping techniques, tape stripping and cyanoacrylate skin surface biopsy, were combined and evaluated. Tape stripping was used to remove the part of the stratum corneum that contained the topically applied dye. Subsequently, the follicular contents were ripped off by cyanoacrylate skin surface biopsy. The combined method termed "differential stripping" was evaluated in vitro and in vivo , and the amount of topically applied fluorescent dye penetrated into the hair follicles was quantified after different penetration times. After 30 min, 5% of the recovered concentration of sodium fluorescein was found in the follicular infundibula, where it was still detectable after 48 h. Altogether, the results of this investigation revealed that differential stripping is a new method that can be used to study the penetration of topically applied substances into the follicular infundibula non-invasively and selectively.