Histopathologic features of the vagus nerve after electrical stimulation in swine

This paper describes the histological features of the vagus nerve after its stimulation with an electrostimulation system that is being developed for morbid obesity treatment. An electrostimulation system was implanted laparoscopically around the ventral vagal trunk of five Large White female pigs (49.63+/-1.94 kg.). Vagal nerve stimulation was performed by continuous constant voltage current pulses. Thoracic samples of both ventral and dorsal vagal trunks were obtained thoracoscopically one month after implantation. Animals were sacrificed one month after thoracoscopic vaguectomy. Tissue samples were then harvested from the vagal nerve at the implantation site, 1cm cranial to it, thoracic portion of ventral and dorsal vagal trunks, sub-diaphragmatic dorsal vagal trunk, left and right vagus nerves. Specimens were analysed with light microscope. The severity of the lesions was graded from 0 to 4 (0: no lesion, 1: mild, 2: moderate, 3: severe and 4: extremely severe), taking into account fibrosis, vascularization, necrosis, fiber degeneration and inflammation. Electrode implantation resulted in thickened epineurium and endoneural connective tissue. The greatest lesion score was evidenced at the leads implantation site in the ventral vagal trunk, followed by, in order of decreasing lesion severity, left vagus nerve, thoracic portion of ventral vagal trunk, subdiaphragmatic dorsal vagal trunk, thoracic portion of dorsal vagal trunk and right vagus nerve. The stimulation device used in this study caused connective tissue growth, greatest in the samples located closer to the implantation site. However, there was no sign of altered vascularization in any studied specimen.     

A crucial role for antigen-presenting cells and alloantigen expression in graft-versus-leukemia responses

Graft-versus-leukemia (GVL) response after allogeneic bone marrow transplantation (BMT) represents one of the most potent forms of immunotherapy against malignant diseases. Antigen-presenting cells (APCs) are crucial for the induction of graft-versus-host disease (GVHD), the most serious complication of allogeneic BMT, but their role in GVL responses is unclear. Using a series of clinically relevant mouse GVL tumor models, we found that APCs and alloantigen expression on tumors are crucial for GVL. Moreover, APCs of host origin predominated in GVL responses although donor APCs contributed as the acuity of tumor burden decreased.     

Nonmuscle myosin heavy-chain gene MYH14 is expressed in cochlea and mutated in patients affected by autosomal dominant hearing impairment (DFNA4)

Myosins have been implicated in various motile processes, including organelle translocation, ion-channel gating, and cytoskeleton reorganization. Different members of the myosin superfamily are responsible for syndromic and nonsyndromic hearing impairment in both humans and mice. MYH14 encodes one of the heavy chains of the class II nonmuscle myosins, and it is localized within the autosomal dominant hearing impairment (DFNA4) critical region. After demonstrating that MYH14 is highly expressed in mouse cochlea, we performed a mutational screening in a large series of 300 hearing-impaired patients from Italy, Spain, and Belgium and in a German kindred linked to DFNA4. This study allowed us to identify a nonsense and two missense mutations in large pedigrees, linked to DFNA4, as well as a de novo allele in a sporadic case. Absence of these mutations in healthy individuals was tested in 200 control individuals. These findings clearly demonstrate the role of MYH14 in causing autosomal dominant hearing loss and further confirm the crucial role of the myosin superfamily in auditive functions.     

N-[1-Aryl-2-(1-imidazolo)ethyl]-guanidine derivatives as potent inhibitors of the bovine mitochondrial F1F0 ATP hydrolase

A series of substituted guanidine derivatives were prepared and evaluated as potent and selective inhibitors of mitochondrial F(1)F(0) ATP hydrolase. The initial thiourethane derived lead molecules possessed intriguing in vitro pharmacological profiles, though contained moieties considered non-drug-like. Analogue synthesis efforts led to compounds with maintained potency and superior physical properties. Small molecules in this series which potently and selectivity inhibit ATP hydrolase and not ATP synthase may have utility as cardioprotective agents.     

Intra- and interspecific competition between biotypes B and Q of Bemisia tabaci (Hemiptera: Aleyrodidae) from Spain

Biotypes B and Q of Bemisia tabaci (Gennadius), collected from the islands of Tenerife and Majorca respectively, were exposed to competition conditions on tomato cv. Marmande in the laboratory. Both biotypes were established in single and mixed cultures at different densities. Increased mortality of biotype Q females and immature instars was observed together with a lower rate of fecundity and progeny size compared to biotype B, when reared in single or mixed cultures. The female:male sex ratio of F1 individuals of biotype Q was higher in single than in mixed cultures. However, the sex ratio of F1 individuals of biotype B was the same in single and mixed cultures, suggesting reproductive interference. Whitefly density did not affect interspecific interactions. It had a moderate effect on developmental rate of both biotypes, and on mortality of immature instars and progeny size of biotype B only. The results indicate that under laboratory conditions the studied biotype B should displace biotype Q.     

beta-Endorphin: characteristics of binding sites in the rat brain.

Stereospecific binding of human β-endorphin to rat membrane preparations is described for the first time using $\text{[}{}^3\text{H-Tyr}{}^{27}\text{]-β}{}_{\mathrm{h}}\text{-endorphin}$ as the ligand. The binding is time dependent and saturable with respect to β_h-endorphin with an apparent dissociation constant of 0.3 nM. Sodium ion (100 mM) elevates this value to 2.5 nM but has no effect on the total number of binding sites present in the membrane preparation. The ability of certain β-endorphin analogs, opiate agonists as well as antagonists to inhibit the binding of β_h-endorphin, is presented.     

A novel neurotoxoid vaccine prevents mucosal botulism

The threat posed by botulism, classically a food- and waterborne disease with a high morbidity and mortality, has increased exponentially in an age of bioterrorism. Because botulinum neurotoxin (BoNT) could be easily disseminated by terrorists using an aerosol or could be used to contaminate the food or water supply, the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases has classified it as a category A agent. Although clearly the development of a safe and effective mucosal vaccine against this toxin should be a high priority, essentially no studies to date have assessed mucosal immune responses to this disease. To bridge this gap in our knowledge, we immunized mice weekly for 4 wk with nasal doses of BoNT type A toxoid and a mutant of cholera toxin termed E112K. We found elevated levels of BoNT-specific IgG Abs in plasma and of secretory IgA Abs in external secretions (nasal washes, saliva, and fecal extracts). When mice given nasal BoNT vaccine were challenged with 4 x 10(3) LD50 of BoNT type A (BoNT/A) via the i.p. route, complete protection was seen, while naive mice given the same dosage died within 2 h. To further confirm the efficacy of this nasal BoNT vaccine, an oral LD50 was determined. When mice were given an oral challenge of 5 microg (2 x oral LD50) of progenitor BoNT/A, all immunized mice survived beyond 5 days, while nonimmunized mice did not. The fecal extract samples from nasally vaccinated mice were found to contain neutralizing secretory IgA Abs. Taken together, these results show that nasal BoNT/A vaccine effectively prevents mucosal BoNT intoxication.     

Biopesticide effect of green compost against fusarium wilt on melon plants

AIMS: The biopesticide effect of four green composts against fusarium wilt in melon plants and the effect of soil quality in soils amended with composts were assayed. METHODS AND RESULTS: The composts consisted of pruning wastes, with or without addition of coffee wastes (3/1 and 4/1, dry wt/dry wt) or urea (1000/1, dry wt/dry wt). In vitro experiments suggested the biopesticide effect of the composts against Fusarium oxysporum, while only the compost of pine bark and urea (1000/1dry wt/dry wt) had an abiotic effect. Melon plant growth with composts and F. oxysporum was one to four times greater than in the non-amended soil, although there was no significant decrease in the level of the F. oxysporum in the soil. The addition of composts to the soil also improved its biological quality, as assessed by microbiological and biochemical parameters: ATP and hydrolases involved in the P (phosphatase), C (beta-glucosidase) and N (urease) cycles. CONCLUSIONS: Green composts had greater beneficial characteristics, improved plant growth and controlled fusarium wilt in melon plants. These composts improve the soil quality of semi-arid agricultural soils. SIGNIFICANCE AND IMPACT OF THE STUDY: Biotic and abiotic factors from composts have been tested as responsible of their biopesticide activity against fusarium wilt.     

Diterpenoids from Ajuga chamaepitys: Two neo-clerodane derivatives

From the whole plant of Ajuga chamaepitys two new neo-clerodane diterpenoids, ajugapitin and its dihydro derivative, have been isolated. Their