Immunological mechanisms giving rise to latency of herpes simplex virus in the spinal ganglia of the mouse

In the model of genital herpes simplex virus (HSV)-infection of mice, early latency could be induced by passive immunization with HSV-specific antibodies and, to a lesser degree, by adoptive transfer of immune lymphocytes prepared from spleen and draining lymph nodes of genitally infected syngeneic mice. Conversely, spontaneously occurring latency was inhibited by treatment of the animals with cyclophosphamide (Cph) and, to a lesser degree, with cyclosporin A (CyA). Whereas the effect of CyA could be compensated by passively administered HSV-specific antibodies, that of Cph could not. Apparently specific antibodies cooperate with a non-specific proliferating cell type, probably macrophages and/or NK-cells, as could be demonstrated by significantly reduced antibody effect in silica-treated mice. Moreover, F(ab)₂ fragments, in contrast to complete antibody molecules, were inactive. HSV-specific antibodies and also immune lymphocytes had little effect on virus production in the mucous membranes, immune lymphocytes being at least as active as antibodies. It is therefore not probable that latency is induced by attenuation of the peripheral disease. It can rather be concluded that the neuron itself is the target for the action of specific antibodies, cooperating in turn with macrophages and/or NK cells.With support of the Deutsche Forschungsgemeinschaft, Schn 174/6-3     

Lipid-drug conjugate nanoparticles of the hydrophilic drug diminazene-cytotoxicity testing and mouse serum adsorption.

Sleeping sickness is a widely distributed disease in great parts of Africa. It is caused by Trypanosoma brucei gambiense and rhodiense, transmitted by the Tse-Tse fly. After a hemolymphatic stage, the parasites enter the central nervous system where they cannot be reached by hydrophilic drugs. To potentially deliver the hydrophilic antitrypanosomal drug diminazene diaceturate to the brain of infected mice, the drug was formulated as lipid-drug conjugate (LDC) nanoparticles (NP) by combination with stearic- (SA) and oleic acid (OA). To estimate the in vivo compatibility, the particles were incubated with human granulocytes. Because as potential delivery mechanism the absorption of specific serum proteins (ApoE, Apo AI and Apo AIV) was found to be responsible for the delivery of nanoparticles to the brain, demonstrated using PBCA nanoparticles coated with polysorbate 80 (LDL uptake mechanism) the nanoparticles were incubated with mouse serum and the adsorption pattern was determined using the 2-D PAGE technique. As a result of this study, the cytotoxic potential was shown to decrease when diminazene is part of the particle matrix compared to pure fatty acid nanoparticles and the mouse serum protein adsorption pattern differs from the samples studied earlier in human serum. Especially, the fact concerning Apo-E that could be detected when the particles were incubated in human serum is absent after the mouse serum incubation, potentially, is a critical point for the delivery via the LDL-uptake mechanism but the data demonstrate that LDC nanoparticles, with 33% (wt/wt) drug loading capacity possess the potential to act as a delivery system for hydrophilic drugs like diminazene diaceturate and that further studies have to demonstrate the usability as a brain delivery system.     

Alcohol-induced heart rate response dampening during aversive and rewarding stress paradigms in subjects at risk for alcoholism.

Individuals with a family history of alcoholism (FH+) are at risk to develop alcohol problems. In several studies, psychophysiological stress responses were more attenuated by alcohol in FH+ than in FH- subjects. However, it is not clear from these studies, if this stronger stress-response dampening effect of alcohol (SRD) in FH+ subjects is confined to aversive stimuli, or would hold for nonaversive stress conditions as well. Also, male and female FH+ subjects seem to respond differently to the alcohol challenge, but have rarely been directly compared in a SRD paradigm. Participants were 54 female and 63 male healthy adults; 31 women were daughters (DOAs) and 40 men were sons (SOAs) of alcohol-dependent fathers. The remaining 23 women (DONAs) and 23 men (SONAs) had no FH of any alcohol use disorder. The participants took part in two laboratory sessions, one with and one without alcohol. In each session, three stressor procedures were presented. Heart rate is the main dependent variable in this report. SOAs, but not SONAs showed a tendency towards SRD. Among female participants, a strong SRD occurred, but contrary to our expectation only in controls. Stress responses and SRD effects were somewhat stronger in the aversive than in the rewarding task. The extent of alcohol induced SRD was strongly influenced by BAL and the amplitude of the stress response in the no-alcohol condition (multiple regression analysis). Thus, aversive tasks might have the advantage of eliciting stronger stress responses than rewarding tasks, thereby providing better conditions for observing differences in alcohol induced SRD between FH+ and FH- subjects.     

Treatment of cremaster synkinesias with botulinum toxin A: a video case report.

Synkinesias secondary to nerve lesions and aberrant re-innervation are well-known phenomena especially after lesions of the facial nerve. Synkinesias can successfully be treated with botulinum toxin A (BTx A). Synkinesias of the cremaster muscle have not been described or treated to date. We present the case of a 62-year-old man who developed synkinesias of both cremaster muscles after extensive laparatomy for esophageal cancer. Treatment of synkinesias with various oral medications had been unsuccessful. Electromyography-guided injections of BTx A in both cremaster muscles (15 MU on the right and 10 on the left) led to significant symptom relief for an average of 8 weeks. We present the case including pre- and posttreatment video clips.     

Temperature-influenced ordering of mesogens in comb-like liquid-crystalline poly(methylsiloxane) macromolecules with side groups consisting of “phenyl benzoate” moieties in solution

Comb-like poly(methylsiloxane) macromolecules P4, P6, and P11, with side groups consisting of “phenyl benzoate” moieties and different alkyl spacers (from 4 to 11 C-atoms) between the backbone and the mesogenic side groups have been synthesized and investigated as well as low-molar-mass compounds M4, M6, and M11, as model molecules analogous to side chains of the macromolecule. The liquid-crystalline phase transition temperatures have been determined. Mobility of the mesogens and the macromolecule as a whole in dilute solution was studied in external fields (electric and mechanical shear field). In dilute solution under the influence of a sinusoidal electric field, the polymer behaviour is typical of flexible-chain polymer molecules where each mesogenic unit is oriented independently of the other ones. This is in contrast to the effect observed in a mechanical shear flow field. The Maxwell constant in positive for the solutions of compounds M4, M6, M11 and negative in polymers P4, P6, P11. This indicates the orientation of the macromolecule as a whole in the shear flow field, the mesogenic group main axis being oriented in the direction preferably normal to the macromolecular axis of primary polarizability. Temperature effects are also discussed.     

Cardinal points and image–object magnification with an accommodative lens implant (1 CU)

A simple mathematical method for the determination of the cardinal points of pseudophakic eyes after implantation of an accommodative intraocular lens [posterior chamber intraocular lenses (PCIOL)] is presented. The purpose of this study was to explore the changes during pseudophakic accommodation (PAC) in (1). the positions of the cardinal points, (2). the distance of the object conjugate with the retina, and (3). the image-object magnification. These theoretical accommodation data are compared with clinical measurements. METHODS AND PATIENTS: Using biometrical measurements of the axial length, equivalent power of the cornea and the anterior chamber depth (ACD) in the non-accommodated state we used linear geometric optics for determination of the cardinal points and object distance as well as lateral magnification (the ratio of image to object size). With the measurement of ACD decrease (following pharmacological stimulation of the ciliary muscle with 2% pilocarpine eye drops) we determined the changes of the cardinal points and magnification to assess PAC amplitude from the shortening of the object distance. Calculated values of PAC amplitude were compared with the respective measured values derived from amplitude measures by accommodometer, defocusing and streak retinoscopy. We analysed the results of a prospective study on 35 eyes of 28 patients after cataract surgery (target refraction: -0.2 D) and accommodative PCIOL implantation (1 CU, Human Optics AG, Erlangen, Germany) 3 months after surgery. RESULTS: After pilocarpine eye drops, ACD (mean +/- S.D., range; median) decreased by 0.88 +/- 0.48 mm (0.51-1.91; 0.66). Distance of the in-focus object decreased from the non-accommodated state (-5.62 +/- 1.83 m, -25 to -1.1; -4.83 m) to the accommodated state (ACD decrease) (-0.81 +/- 0.21, -2.11 to -0.65; -0.79 m). For a theoretical ACD decrease of 1.0 mm (the intrinsic limitation of the PCIOL design) it was -0.59 +/- 0.28, -1.31 to -0.51; -0.63 m and resulted in an objective accommodative response of 1.49 +/- 0.16, 1.21-1.81; 1.46 D, depending on the actual geometry of the individual eye. On average, magnification as induced by PAC in contrast to that induced by adequate spectacle addition differed by only about 1%. Accommodation measured with defocusing and the accommodometer correlated significantly with the theoretical value based on IOLMaster measurement of ACD decrease (r = 0.752, p = 0.005 and r = 0.676, p = 0.02). Likewise, accommodation measured with streak retinoscopy correlated weakly with the theoretical value based on IOLMaster ACD decrease (r = 0.465, p = 0.05). CONCLUSIONS: Using geometrical optics, PAC can be derived from the biometric data of the eye and the measured ACD decrease. This approach may be an additional indicator for the accommodative response in pseudophakic patients and may allow a subdivision of the measured accommodation into true PAC and pseudoaccommodation, for example, because of increased depth of focus induced by pupillary constriction.