Neuropathy in Parkinson's disease patients with intestinal levodopa infusion versus oral drugs.

BACKGROUND: Severe polyneuropathy has been observed in a number of patients treated for Parkinson's disease with Levodopa/Carbidopa intestinal gel infusion. This may reflect a rare individual complication or a systematic side effect. OBJECTIVE: To investigate whether peripheral nerve function differed between patients with oral treatment versus Levodopa/Carbidopa intestinal gel infusion. METHODS: In an observational design, data from median, tibial, and peroneal neurography were prospectively assessed and compared between patients with conventional drug treatment (n = 15) and with Levodopa/Carbidopa intestinal gel infusion (n = 15). The groups were matched for age and disease duration. In view of the medical risk profile for polyneuropathy, comorbidity and basic serological parameters were assessed. RESULTS: Axonal neuropathy was common in both patient groups. However, although group differences in risk factors for polyneuropathy were not evident, neurographic abnormalities were more severe in the patients treated with Levodopa/Carbidopa intestinal gel infusion than in the orally treated patients. In the group with Levodopa/Carbidopa intestinal gel infusion, the degree of neuropathic change correlated with weight lost since therapy initiation and with the drug dose. In contrast to the axonal abnormalities, conduction velocity was found normal in both groups. CONCLUSION: The results are compatible with the promotion of axonal neuropathy by Levodopa/Carbidopa intestinal gel infusion. This could be due to the intrinsically high levodopa doses associated with the therapy and/or malnutritional effects from intestinal drug application. The results should be corroborated by a larger longitudinal and controlled trial

Epithelial cell lines of the cotton rat (<i>Sigmodon hispidus</i>) are highly susceptible in vitro models to zoonotic <i>Bunya-</i>, <i>Rhabdo-</i>, and <i>Flaviviruses</i>

Background: Small mammals such as bats and rodents have been increasingly recognized as reservoirs of novel potentially zoonotic pathogens. However, few in vitro model systems to date allow assessment of zoonotic viruses in a relevant host context. The cotton rat (Sigmodon hispidus) is a New World rodent species that has a long-standing history as an experimental animal model due to its unique susceptibility to human viruses. Furthermore, wild cotton rats are associated with a large variety of known or potentially zoonotic pathogens. Methods: A method for the isolation and culture of airway epithelial cell lines recently developed for bats was applied for the generation of rodent airway and renal epithelial cell lines from the cotton rat. Continuous cell lines were characterized for their epithelial properties as well as for their interferon competence. Susceptibility to members of zoonotic Bunya-, Rhabdo-, and Flaviviridae, in particular Rift Valley fever virus (RVFV), vesicular stomatitis virus (VSV), West Nile virus (WNV), and tick-borne encephalitis virus (TBEV) was tested. Furthermore, novel arthropod-derived viruses belonging to the families Bunya-, Rhabdo-, and Mesoniviridae were tested. Results: We successfully established airway and kidney epithelial cell lines from the cotton rat, and characterized their epithelial properties. Cells were shown to be interferon-competent. Viral infection assays showed high-titre viral replication of RVFV, VSV, WNV, and TBEV, as well as production of infectious virus particles. No viral replication was observed for novel arthropod-derived members of the Bunya-, Rhabdo-, and Mesoniviridae families in these cell lines. Conclusion: In the current study, we showed that newly established cell lines from the cotton rat can serve as host-specific in vitro models for viral infection experiments. These cell lines may also serve as novel tools for virus isolation, as well as for the investigation of virus-host interactions in a relevant host species.</p

Correlation of daily levodopa dose and the number of neurographically impaired nerves.

<p>The daily levodopa dose is indicated on the abscissa, the number of neurographically impaired nerves on the ordinate. Triangles and dots reflect the values of the orally treated and LCIG patients respectively. The regression line is provided for the data from the LCIG group for which the correlation coefficient (r) was significantly higher than in the orally treated group.</p

Correlations between the number of impaired nerves and patient parameters.

<p>The first two data columns provide the correlation values per parameter in each group. The last column indicates the p-values for the comparisons of the correlation coefficients between the groups (reflecting the probability of erroneously assuming distinct correlations in LCIG versus orally treated patients).</p><p>LD: levodopa dose.</p><p>LED: levodopa equivalence dose.</p><p>numbers: Spearman rank correlation (with asterisk: p<0.05).</p><p>Δ (p-value): probability of erroneously assuming different correlations between the groups.</p

Laboratory results in LCIG and orally treated patients.

<p>ESR: erythrocyte sedimentation rate; HbA₁c: glycated haemoglobin, TSH: thyroid-stimulating hormone; ALT: alanine transaminase, AST: aspartate transaminase; GGT: gamma-glutamyltransferase; ANA: anti-nuclear antibodies last column: p-values for group comparisons per parameter Data provided as mean values ± standard deviation.</p

Bat Airway Epithelial Cells: A Novel Tool for the Study of Zoonotic Viruses

<div><p>Bats have been increasingly recognized as reservoir of important zoonotic viruses. However, until now many attempts to isolate bat-borne viruses in cell culture have been unsuccessful. Further, experimental studies on reservoir host species have been limited by the difficulty of rearing these species. The epithelium of the respiratory tract plays a central role during airborne transmission, as it is the first tissue encountered by viral particles. Although several cell lines from bats were established recently, no well-characterized, selectively cultured airway epithelial cells were available so far. Here, primary cells and immortalized cell lines from bats of the two important suborders Yangochiroptera and Yinpterochiroptera, <i>Carollia perspicillata</i> (Seba's short-tailed bat) and <i>Eidolon helvum</i> (Straw-colored fruit bat), were successfully cultured under standardized conditions from both fresh and frozen organ specimens by cell outgrowth of organ explants and by the use of serum-free primary cell culture medium. Cells were immortalized to generate permanent cell lines. Cells were characterized for their epithelial properties such as expression of cytokeratin and tight junctions proteins and permissiveness for viral infection with Rift-Valley fever virus and vesicular stomatitis virus Indiana. These cells can serve as suitable models for the study of bat-borne viruses and complement cell culture models for virus infection in human airway epithelial cells.</p></div

Virus infection studies with vesicular stomatitis virus (VSV) (A, B) and Rift Valley fever virus (RVFV) (C, D), and at MOI of 0.1 (left side) and 0.001 (right side), in subclones of immortalized <i>C. perspicillata</i> airway epithelial cells (subclone 3, designated CarperAEC.B-3) and <i>E. helvum</i> airway epithelial cells (subclone 1, designated EidheAEC.B-1).

<p>Viruses were detected by quantitative real-time RT-PCR. All cells were infectable and able to support replication of RVFV and VSV.</p