Diffusion-weighted imaging study of patients with essential tremor.

The pathophysiology of essential tremor (ET) is unknown. PET and fMRI studies have revealed bilateral activation and (1)H-MRS studies metabolic abnormalities in the cerebellum and other functionally related brain structures in ET. Diffusion-weighted imaging (DWI) was used to search for evidence of tissue integrity abnormalities in these areas in ET patients and 10 matched controls by calculating water apparent diffusion coefficients (ADCs). Regions of interest included the left and right cerebellum, red nucleus, thalamus, caudate, putamen, pallidum, and frontal white matter. Histograms of ADCs were generated for all pixels in the infratentorial compartment and manually segmented areas corresponding to brainstem, vermis, and cerebellar hemispheres. ADC values were similar in all brain areas in patients and controls. Our study did not detect changes affecting the investigated brain regions in ET patients. These findings argue against major structural damage in the ET brain, although more subtle neurodegenerative changes cannot be ruled out.     

Inhaltsstoffe von Fagaceae (Cupuliferae), 19. Mitt.: Triterpensaponine und Acylflavonoide aus Quercus robur var. stenocarpa Beck.

Constituents of Fagaceae (Cupuliferae), XIX: Triterpene Saponins and Acylated Flavonoids from Quercus robur L. var. stenocarpa Beck. In addition to four known glycosides from leaves of Quercus robur L. var. stenocarpa Beck. a new triterpene saponin has been isolted and identified as 28-β-d-glucopyranosyl ester of the 2α,3β,19α-trihydroxy-olean-12-ene-24,28-dioic acid ( I ).     

Oligofurostanosides from Asparagus cochinchinensis

The aqueous extract of ASPARAGUS COCHINCHINENSIS yielded a new oligofurostanoside 3- O-[alpha- L-rhamnopyranosyl-(1-->4)-beta- D-glucopyranosyl]-26- O-(beta- D-glucopyranosyl)-(25 R)-furosta-5,20-diene,-3beta,26-diol as well as two known furostanosides, methylprotodioscin and pseudoprotodioscin.     

Induction of antigen-specific antibodies in vaginal secretions by using a nontoxic mutant of heat-labile enterotoxin as a mucosal adjuvant.

Immunization of the female reproductive tract is important for protection against sexually transmitted diseases and other pathogens of the reproductive tract. However, intravaginal immunization with soluble antigens generally does not induce high levels of secretory immunoglobulin A (IgA). We recently developed safe mucosal adjuvants by genetically detoxifying Escherichia coli heat-labile enterotoxin, a molecule with a strong mucosal adjuvant activity, and here we describe the use of the nontoxic mutant LTK63 to induce a response in the mouse vagina against ovalbumin (Ova). We compared intravaginal and intranasal routes of immunization for induction of systemic and vaginal responses against LTK63 and Ova. We found that LTK63 is a potent mucosal immunogen when given by either the intravaginal or intranasal route. It induces a strong systemic antibody response and IgG and long-lasting IgA in the vagina. The appearance of vaginal IgA is delayed in the intranasally immunized mice, but the levels of vaginal anti-LTK63 IgA after repeated immunizations are higher in the intranasally immunized mice than in the intravaginally immunized mice. LTK63 also acts as a mucosal adjuvant, inducing a serum response against Ova, when given by both the intravaginal and intranasal routes. However, vaginal IgA against Ova is stimulated more efficiently when LTK63 and antigen are given intranasally. In conclusion, our results demonstrate that LTK63 can be used as a mucosal adjuvant to induce antigen-specific antibodies in vaginal secretions and show that the intranasal route of immunization is the most effective for this purpose.     

Characterization of genetically inactivated pertussis toxin mutants: candidates for a new vaccine against whooping cough.

the introduction of two amino acid substitutions within the enzymatically active subunit S1 of pertussis toxin (PT) abolishes its ADP-ribosyltransferase activity and toxicity on CHO cells (Pizza et al., Science 246:497-500, 1989). These genetically inactivated molecules are also devoid of other in vivo adverse reactions typical of PT, such as induction of leukocytosis, potentiation of anaphylaxis, stimulation of insulin secretion, and histamine sensitivity. However, the mutant PT molecules are indistinguishable from wild-type PT in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and maintain all the physical and chemical properties of PT, including affinity for toxin-neutralizing poly- and monoclonal antibodies. Either alone or stabilized with formaldehyde, PT mutants are able to induce high levels of neutralizing antibodies and to protect mice in a dose-dependent fashion against intracerebral challenge with virulent B. pertussis. These results clearly show that these genetically inactivated PT molecules are nontoxic but still immunogenic and justify their development as a component of a new, safer acellular vaccine against whooping cough.     

Protective levels of diphtheria-neutralizing antibody induced in healthy volunteers by unilateral priming-boosting intranasal immunization associated with restricted ipsilateral mucosal secretory immunoglobulin a

Subunit intranasal vaccines offer the prospect of inducing combined systemic-mucosal immunity against mucosally transmitted infections such as human immunodeficiency virus. However, although human studies have demonstrated the induction of active immunity, secretory immunoglobulin A (sIgA) responses are variable, and no study has demonstrated protection by accepted vaccine-licensing criteria as measured by direct toxin-neutralizing activity. Using the genetically inactivated mutant diphtheria toxoid CRM(197) in a bioadhesive polycationic polysaccharide chitosan delivery system, we found that a single nasal immunization was well tolerated and boosted antitoxin neutralizing activity in healthy volunteers, which could be further boosted by a second immunization. The neutralizing activity far exceeded accepted protective levels and was equivalent to that induced by standard intramuscular vaccine and significantly greater than intranasal immunization with CRM(197) in the absence of chitosan. A striking but unexpected observation was that although unilateral intranasal immunization induced circulating antitoxin antibody-secreting cells, a nasal antitoxin sIgA response was seen only after the second immunization and only in the vaccinated nostril. If these data are reproduced in larger studies, an intranasal diphtheria vaccine based on CRM(197)-chitosan could be rapidly licensed for human use. However, a restricted sIgA response suggests that care must be taken in the priming-boosting strategy and clinical sampling techniques when evaluating such vaccines for the induction of local mucosal immunity.     

Umbelliferose from Cachrys ferulacea Seeds: Determination of the Sugar Sequence by NMR 2D-COLOC Technique

Umbelliferose has been isolated from the fruits of CACHRYS FERULACEA (L.) Calestani and the sugar sequence has been determined by NMR spectroscopic 2D-COLOC technique. The method of identification of the trisaccharide, which occurs only in the Umbelliferae family and may have a chemotaxonomic significance, is described and briefly discussed.     

Anti-inflammatory doses of ibuprofen: effect on neutrophils and exercise-induced muscle injury

The purpose of the study was to determine the effect of anti-inflammatory doses of ibuprofen on neutrophils, neutrophil O2* production, and markers of muscle injury. Males (n=10) performed 2 bouts of one-arm eccentric exercise on opposite arms separated by three weeks. Subjects received 2400 mg x d(-1) of ibuprofen or a placebo 5 d before exercise and during 10 d of recovery. Measurements were made before the treatments, pre-exercise, at 4 h, and at 1, 2, 3, 4 and 10 d post-exercise. Circulating neutrophil counts were similar between the treatments at the sampling points. Neutrophil counts were higher (p<0.05) for ibuprofen and were elevated (p<0.05) at 4h post-exercise relative to pre-exercise in both treatments. Stimulated neutrophil O2* production was lower for ibuprofen relative to placebo at pre-exercise and was increased (p<0.05) at 4 h and 4 d of both treatments. CK activity at 3 d post-exercise was lower (p<0.05) for ibuprofen relative to placebo. Isometric strength, soreness, tenderness, and arm angles were similar between the treatments. In conclusion, anti-inflammatory doses of ibuprofen reduced CK activity but not the neutrophil response or other indirect markers of muscle injury during recovery from eccentric arm exercise.