Long-term effects of spinal transection of the development and function of sympathetic ganglia

The long-term effect of interruption of descending central pathways on the biochemical development and function of sympathetic neurons was examined in the sixth lumbar (L6) sympathetic ganglia of the rat. Previous investigations had defined the normal maturation of presynaptic choline acetyltransferase (CAT) activity, postsynaptic tyrosine hydroxylase (T-OH) activity and total protein in L6 ganglia. Neonatal spinal cord transection prevented the normal ontogeny of CAT activity: enzyme activity was 40% of control one week and one year after surgery. Similarly, T-OH activity failed to develop normally after transection and was 22% of control one year postoperatively. Spinal transection at 30 days of age did not alter baseline CAT or T-OH activities in L6 ganglia when examined up to 6 months after surgery. Apparently during the first month of life descending central pathways exert critical facilitatory influences on sympathetic ganglia maturation; interruption of these influences results in long-lasting biochemical deficits. We also examined the role of central mechanisms in adult sympathetic function. Stressful stimuli, including reserpine treatment, normally induce adult T-OH through reflex sympathetic activation. This biochemical adaptability was studied by treating rats with reserpine after spinal transection. After motor and autonomic spinal reflexes returned in paraplegic animals, reserpine treatment was initiated. Spinal animals did not exhibit T-OH induction. These observations indicate that central rather than spinal mechanisms govern this biochemical adaptability of mature sympathetic neurons.     

Steady state plasma levels of the enantiomers of trimipramine and of its metabolites in CYP2D6-, CYP2C19- and CYP3A4/5-phenotyped patients

Steady state plasma concentrations of the (L)- and (D)-enantiomers of trimipramine (TRI), desmethyltrimipramine (DTRI), 2-hydroxytrimipramine (TRIOH) and 2-hydroxydesmethyl-trimipramine (DTRIOH) were measured in 27 patients receiving between 300 and 400 mg/day racemic TRI. The patients were phenotyped with dextromethorphan and mephenytoin, and the 8-hour urinary ratios of dextromethorphan/dextrorphan, dextromethorphan/3-methoxymorphinan, and (S)-mephenytoin/(R)mephenytoin were used as markers of cytochrome P-450IID6 (CYP2D6), CYP3A4/5 and CYP2C19 activities, respectively. One patient was a CYP2D6 and one was a CYP2C19 poor metabolizer. A stereoselectivity in the metabolism of TRI has been found, with a preferential N-demethylation of (D)-TRI and a preferential hydroxylation of (L)-TRI. CYP2D6 appears to be involved in the 2-hydroxylation of (L)-TRI, (L)DTRI and (D)-DTRI, but not of (D)-TRI, as significant correlations were measured between the dextromethorphan/dextrorphan ratios and the (L)-TRI/(L)-TRIOH (r = 0.45, p = 0.019), the (L)-DTRI/(L)-DTRIOH (r = 0.47, p = 0.014), and the (D)-DTRI/(D)-DTRIOH (r = 0.51, p = 0.006), but not with the (D)-TRI/(D)-TRIOH ratios (r = 0.29, NS). CYP2C19, but not CYP2D6, appears to be involved in the demethylation pathway, with a stereoselectivity toward the (D)-enantiomer of TRI, as a significant positive correlation was calculated between the mephenytoin (S)/(R) ratios and the concentrations to dose-to-weight ratios of (D)-TRI (r = 0.69, p = 0.00006). CYP3A4/5 appears to be involved in the metabolism of (L)-TRI to a presently not determined metabolite. The CYP2D6 poor metabolizer had the highest (L)-DTRI and (D)-DTRI concentrations to dose-to-weight ratios, and the CYP2C19 poor metabolizer had the highest (L)-TRI and (D)-TRI concentrations to dose-to-weight ratios of the group.     

Nerve fiber growth in culture on tissue substrata from central and peripheral nervous systems

In adult mammals, injured neurons regenerate extensively within the PNS but poorly, if at all, within the CNS. We have studied the effect of substrata consisting of tissue sections from various nervous systems on nerve fiber growth in culture and correlated our results with the growth potential of these tissues in vivo. Ganglionic explants from embryonic chicks (9-12 d) fail to extend nerve fibers onto sections of adult rat optic nerve or spinal cord (CNS) but do so on sciatic nerve (PNS). Dissociated DRG neurons behave similarly whether in serum-containing or defined medium. Tissue substrata from nervous systems that support regeneration in vivo--i.e., goldfish optic nerve, embryonic rat spinal cord, degenerating sciatic nerve--also support fiber growth in culture. Within the same culture, neurons will grow onto sciatic nerve rather than neighboring optic nerve sections, suggesting that the responsible agent(s) is not soluble. In addition, neurons adhere more extensively to sciatic nerve substrata than to optic nerve. The occurrence of 3 molecules known to be involved in neuron-substratum adhesion and nerve fiber growth in vitro has been documented immunocytochemically in the tissue sections. One of these, laminin, is demonstrable in all tissues tested that supported nerve fiber growth. Immunoreactivities for fibronectin and heparan sulfate proteoglycan are found in only some of these tissues. None of these 3 molecules can be demonstrated in neural cells of normal adult rat CNS tissue. Our data suggest that these molecules may be important effectors of nerve regeneration in neural tissues.     

Congenital anophthalmias: a case of trisomy 13

Congenital anophthalmia is the result of a lack of development or regression of the primary optic vesicle in utero. It can be isolated or associated with other malformations and can be unilateral or, rarely, bilateral. Different etiologies are usually found such as chromosomal aberrations, gene mutations, toxic agents, and infections. We report a case of bilateral congenital anophthalmia in a setting of a polymalformative syndrome with microcephalia and bilateral lip cleft. Karyotype studies confirmed trisomy 13 known as Patau's syndrome. Trisomy 13 is a rare lethal chromosomal aberration frequently responsible for uni- or bilateral microphthalmia and occasionally for anophthalmia.     

Determination of Genotypic Diversity of Mycobacterium avium Subspecies from Human and Animal Origins by Mycobacterial Interspersed Repetitive-Unit-Variable-Number Tandem-Repeat and IS1311 Restriction Fragment Length Polymorphism Typing Methods

Members of the Mycobacterium avium complex (MAC) are ubiquitous bacteria that can be found in water, food, and other environmental samples and are considered opportunistic pathogens for numerous animal species, mainly birds and pigs, as well as for humans. We have recently demonstrated the usefulness of a PCR-based mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing for the molecular characterization of M. avium subsp. paratuberculosis and M. avium strains exclusively isolated from AIDS patients. In the present study we extended our analysis, based on eight MIRU-VNTR markers, to a strain collection comprehensively comprising the other M. avium subspecies, including M. avium subsp. avium, M. avium subsp. hominissuis, and M. avium subsp. silvaticum, isolated from numerous animal species, HIV-positive and HIV-negative humans, and environmental sources. All strains were fully typeable, with the discriminatory index being 0.885, which is almost equal to that obtained by IS1311 restriction fragment length polymorphism (RFLP) typing as a reference. In contrast to IS1311 RFLP typing, MIRU-VNTR typing was able to further discriminate M. avium subsp. avium strains. MIRU-VNTR alleles strongly associated with or specific for M. avium subspecies were detected in several markers. Moreover, the MIRU-VNTR typing-based results were consistent with a scenario of the independent evolution of M. avium subsp. avium/M. avium subsp. silvaticum and M. avium subsp. paratuberculosis from M. avium subsp. hominissuis, previously proposed on the basis of multilocus sequence analysis. MIRU-VNTR typing therefore appears to be a convenient typing method capable of distinguishing the three main subspecies and strains of the complex and providing new epidemiological knowledge on MAC.The most frequent agents of nontuberculous mycobacterioses belong to the Mycobacterium avium complex (MAC); in particular, M. avium subsp. hominissuis is a frequent agent of human mycobacterioses (12, 25). Members of this subspecies are also frequent infectious agents for pigs, leading to significant economic losses in pig farming, albeit that subspecies produces very low rates of morbidity in this animal species (23, 24). Two other MAC members, M. avium subsp. avium and M. avium subsp. paratuberculosis, are the causative agents of two other important, often fatal (2) animal pathologies, avian tuberculosis (40) and ruminant paratuberculosis (Johne''s disease) (6), respectively. Like other opportunistic agents, M. avium subsp. avium and M. avium subsp. hominissuis are also capable of infecting a wide range of animal species, including cattle, deer, wild boars, goats, and horses (40). In contrast, M. avium subsp. silvaticum is taxonomically very close to M. avium subsp. avium but almost exclusively infects wood pigeons (41).In the particular case of M. avium subsp. hominissuis, strains with similar or identical genotypes are usually found in common between pigs and human patients (26), which does not permit the potential zoonotic risk of this subspecies to be discarded. Moreover, these mycobacteria can be found in environmental sources such as water, biofilms, soil, aerosols, and phagocytic protozoa and amoebae (11), all of which can act as common sources of infection for animals and humans.For epidemiological investigations of MAC, the current reference molecular typing technique is restriction fragment length polymorphism analysis (RFLP) based on the IS1245 (47) and IS1311 (19, 20) insertion sequences. Whereas IS1311 RFLP usually generates clear hybridization patterns, IS1245 RFLP yields complex multiband patterns which are difficult to compare among different experiments and laboratories, mainly because of the heterogeneity in the intensities of the hybridization bands (19, 20, 42). Recently, an even simpler PCR-based molecular typing method, multilocus variable-number tandem-repeat analysis (MLVA), which is based on mycobacterial repetitive elements called mycobacterial interspersed repetitive-unit-variable-number tandem repeats (MIRU-VNTRs) (14, 34, 36, 37), has been described for M. avium subsp. paratuberculosis (38). This method presented better results for the differentiation of strains of this subspecies than those obtained by the standard IS900 RFLP method (38) and showed a promisingly good discrimination index (DI) with a panel of M. avium strains isolated from human AIDS patients (38).In the study described here, we extended that initial study by applying MIRU-VNTR typing to a large strain panel set comprising M. avium subsp. hominissuis, M. avium subsp. avium, and M. avium subsp. silvaticum strains isolated from diverse animal and human sources. Our aim was to further analyze the power of MIRU-VNTR typing to discriminate isolates within these subspecies and to identify possible specific signatures within the complex for better characterization and detection of interspecies transmission patterns.     

Impact of norepinephrine on the relationship between pleth variability index and pulse pressure variations in ICU adult patients

Introduction  

Pleth Variability Index (PVI) is an automated and continuous calculation of respiratory variations in the perfusion index. PVI correlates well with respiratory variations in pulse pressure (ΔPP) and is able to predict fluid responsiveness in the operating room. ICU patients may receive vasopressive drugs, which modify vascular tone and could affect PVI assessment. We hypothesized that the correlation between PVI and ΔPP and the ability of PVI to identify patients with ΔPP > 13% is dependent on norepinephrine (NE) use.     

General principles of conception of cochlear implants]

Cochlear implants have greatly been developed on last ten years. Their diversity makes their use and choice more complex. The authors expose simply the physiopathology of the implanted auditory system and basic principles of cochlear implants. Cochlear implants are caracterised by the number of channels and electrodes (monochannel, multichannel), the strategy of encoding (analogiq, digital), the transmission of signal (per-cutaneous, electro-magnetic induction), the site of stimulation (extra or intra-cochlear), the signal wave (sinusoid, pulse), the diffusion of current (monopolar, bipolar).