Tenascin-C expression by neurons and glial cells in the rat spinal cord: Changes during postnatal development and after dorsal root or sciatic nerve injury

Summary We have usedin situ hybridization with a digoxigenin-labelled probe for tenascin-C mRNA and immunocytochemistry with antibodies against tenascin-C, glial fibrillary acidic protein, OX-42 and the 200 kDa neurofilament protein to study the expression, distribution and cellular relationships of tenascin-C mRNA and protein in the developing (postnatal) and adult spinal cord of rat, and the effects thereon of dorsal root, ventral root and sciatic nerve injuries. The most interesting finding was that on postnatal day 7 (P7), P14 and in the adult, but not on P0 or P3, a group of neurons in the lumbar ventral horn expressed the tenascin-C mRNA gene. They represented about 5% of ventral horn neurons in the adult and were among the smaller such neurons. Since 40–60% of such cells were lost at P13 following sciatic nerve crush on P0, some were almost certainly motor neurons. In addition, we found that at P0 and P3, mRNA-containing glial cells were widespread in grey and white matter but sparse in the developing dorsal columns; tenascin-C immunofluorescence showed a similar distribution. By P7 there were fewer mRNA-containing cells in the ventral horns and in the area of the dorsal columns containing the developing corticospinal tract where immunofluorescence was also weak. At P14 there were no glial-like mRNA-containing cells in the grey matter; such cells were confined to the periphery of the lateral and ventral white columns but were present throughout the dorsal columns where tenascin-C immunofluorescence was also strong. No glial-like mRNA-containing cells were present in the adult lumbar spinal cord and tenascin-C immunofluorescence was confined to irregular patches in the ventral horn, especially around immunonegative cell bodies of small neurons, a zone around the central canal, and a thin zone adjacent to the glia limitans. Thus the expression of tenascin-C is differentially developmentally regulated in the grey matter and in different parts of the white matter. Three days after injury of dorsal roots L4–6, many cells containing tenascin-C mRNA, some identified as glial fibrillary acidic protein-positive astrocytes, were present in the ipsilateral dorsal column, but were rare after longer survivals. Immunoreactivity, however, was elevated in the ipsilateral dorsal column at 3 days, remained high for several months and disappeared at 6.5 months. Dorsal root injury had no effect on tenascin-C mRNA or protein in the grey matter. Sciatic nerve or ventral root injury had no effect on these molecules in any part of the spinal cord.     

Evolution and diversity of copy number variation in the great ape lineage

Copy number variation (CNV) contributes to disease and has restructured the genomes of great apes. The diversity and rate of this process, however, have not been extensively explored among great ape lineages. We analyzed 97 deeply sequenced great ape and human genomes and estimate 16% (469 Mb) of the hominid genome has been affected by recent CNV. We identify a comprehensive set of fixed gene deletions (n = 340) and duplications (n = 405) as well as >13.5 Mb of sequence that has been specifically lost on the human lineage. We compared the diversity and rates of copy number and single nucleotide variation across the hominid phylogeny. We find that CNV diversity partially correlates with single nucleotide diversity (r² = 0.5) and recapitulates the phylogeny of apes with few exceptions. Duplications significantly outpace deletions (2.8-fold). The load of segregating duplications remains significantly higher in bonobos, Western chimpanzees, and Sumatran orangutans—populations that have experienced recent genetic bottlenecks (P = 0.0014, 0.02, and 0.0088, respectively). The rate of fixed deletion has been more clocklike with the exception of the chimpanzee lineage, where we observe a twofold increase in the chimpanzee–bonobo ancestor (P = 4.79 × 10⁻⁹) and increased deletion load among Western chimpanzees (P = 0.002). The latter includes the first genomic disorder in a chimpanzee with features resembling Smith-Magenis syndrome mediated by a chimpanzee-specific increase in segmental duplication complexity. We hypothesize that demographic effects, such as bottlenecks, have contributed to larger and more gene-rich segments being deleted in the chimpanzee lineage and that this effect, more generally, may account for episodic bursts in CNV during hominid evolution.Sequence and assembly of great ape reference genomes have consistently revealed that copy number variation (CNV) affects more base pairs than single nucleotide variation (SNV) (Cheng et al. 2005; The Chimpanzee Sequencing and Analysis Consortium 2005; Locke et al. 2011). Segmental duplications, in particular, have disproportionately affected the African great ape (human, chimpanzee, and gorilla) lineages, where they appear to have accumulated at an accelerated rate (Cheng et al. 2005; Marques-Bonet et al. 2009). This has led to speculation that differences in fixation and copy number polymorphism may have contributed to the phenotypic “plasticity” and species-specific differences between humans and great apes (Olson 1999; Varki et al. 2008). While there is some evidence that fixed deletions and duplications contribute to morphological differences between humans and great apes (McLean et al. 2011; Charrier et al. 2012; Dennis et al. 2012), a comprehensive assessment of these differences at the level of the genome has not yet been performed. Previous studies of CNV have been predominated by array comparative genomic hybridization (CGH) experiments (Fortna et al. 2004; Perry et al. 2006; Dumas et al. 2007; Gazave et al. 2011; Locke et al. 2011), which provide limited size resolution, are imprecise in absolute copy number differences, and are biased by probes derived from the human reference genome. Comparisons of reference genomes have been complicated by assessments of a single individual and distinguishing CNVs from assembly errors (The Chimpanzee Sequencing and Analysis Consortium 2005; Locke et al. 2011; Ventura et al. 2011; Prüfer et al. 2012). Here, we compare the evolution and diversity of deletions, duplications, and SNVs in 97 great ape individuals sequenced to high coverage (median ∼25×) (Prado-Martinez et al. 2013). The set includes multiple individuals from the four great ape genera, including Bornean and Sumatran orangutans, each of the four recognized chimpanzee subspecies, bonobos, and both Eastern and Western gorillas, in addition to 10 diverse humans and a high-coverage archaic Denisovan individual. This data set provides unprecedented genome-wide resolution to interrogate multiple forms of genetic variation and a unique opportunity to directly compare mutational processes and patterns of diversity in great apes.     

Anesthetic Efficacy of Meperidine in Teeth With Symptomatic Irreversible Pulpitis

Achieving adequate pulpal anesthesia in mandibular teeth is always a challenge. Supplementary injections and using drugs in combination are some methods implemented to overcome this hurdle. In this randomized clinical trial, use of meperidine in conjunction with lidocaine in intraligamentary injection did not exhibit significant improvement in anesthesia.Key Words: Periodontal ligament, Meperidine, Irreversible pulpitis, Dental anesthesiaThe failure rate of the inferior alveolar nerve block (IANB) in some experimental studies has been reported up to 75%.^1–4 This lack of success has even increased to a maximum of 81% in some recent studies.^5–7 To overcome this shortcoming, dental clinicians have actively sought measures to improve the patients'' anesthesia during different dental procedures. Apart from the anatomical variations mentioned in the applied anatomy of injections,⁸ several authors have attempted to modify the anesthetic technique,^9–12 and others have compared different anesthetic agents¹³ or their concentrations¹⁴ to improve their efficacy.Activating the opioid receptors peripherally in inflammatory conditions has become a new trend in research to manage postoperative pain.¹⁵ Synergy between local anesthetics and opioids has become an interesting field of research recently.¹⁶ Opioids are frequently added to local anesthetics in a variety of surgical procedures, eg, intrathecal application for minor surgery.¹⁷ Meperidine or its derivatives, eg, pethidine (meperidine chloride) or norpethidine (Pethidine Intermediate B) are agonists of μ-opioid receptors, which block the pathway of pain signals to the trigeminal nucleus. They also activate peripheral opioid receptors and block sodium channels.^17–22 Despite controversy regarding the use of meperidine as an anesthetic,²² recent studies have demonstrated its benefits over prilocaine in arthroscopy with local anesthesia,¹⁶ nasal packing removal,²³ etc.However, only a few studies have investigated the dental anesthetic efficacy of such combinations.^24,25 The effect of the addition of meperidine to lidocaine in IANB for pain management in normal teeth²⁴ and also in teeth with irreversible pulpitis²⁵ has been studied. The aim of our study was to compare the efficacy of local anesthetics with and without meperidine for intraligamentary supplemental injection for teeth with irreversible pulpitis. Our null hypothesis stated that the addition of meperidine to standard lidocaine with epinephrine does not improve the efficacy of supplemental intraligamentary anesthesia in teeth with symptomatic irreversible pulpitis. The specific objectives were to randomly allocate volunteers with complete soft tissue anesthesia following an IANB, yet having positive pulp response, into 2 groups, and then compare the efficacy of lidocaine with epinephrine plus meperidine with that of lidocaine with epinephrine plus an equal volume of sterile water for supplemental periodontal ligament anesthesia.     

Menace of childhood non-accidental traumatic brain injuries: A single unit report

Background:

Childhood traumatic brain injury (TBI) has high rate of mortality and morbidity worldwide. There are dearths of reports from developing countries with large paediatric population on trauma; neurosurgery trauma of nonaccidental origin is not an exemption. This study analysed menace of non-accidental TBI in the paediatric population from our center.

Materials and Methods:

This is a single unit, retrospective study of the epidemiology of non-accidental TBI in children starting from September, 2008 to March, 2014. The management outcomes of the epidemiology of the non-accidental TBI were analysed.

Results:

Total of 109 children age range from 0 (intra-natal) to 16 years with a mean of 5.8 ± 4.6 years (median, 5 years) were enrolled into the study. 34 (31.2%) were domestic violence, 26 (23.9%) street assaults, 16 (14.7%) were due to animal assaults and mishaps, 17 (15.6%) fall from heights. Seven (6.4%) cases of collapsed buildings were also seen during the period. Four (3.7%) industrial accidents and two (1.8%) were self-inflicted injuries. There were also three (2.8%) cases of iatrogenic TBI out of which two infants (1.8%) sustained TBI from cesarean section procedure while one patient (0.9%) under general anaesthesia felt from the operation bed resulting to severe TBI.

Conclusion:

Child abuse, unprotected child labour, parental/care-givers negligence are the main cause of nonaccidental TBI. Human right activists and government agents should be incorporated in curtailing the menace.     

AIDS and heart disease: is cardiac surgery justified?

A compromised immune system, limited survival and increased risk to the anaesthetic and surgical team of acquiring HIV infection have been the major concerns in offering cardiac surgery to patients with AIDS. The current report presents a patient with AIDS who underwent successful, uncomplicated coronary artery surgery. He remains free of ischaemic and any infectioe symptoms 12 months postoperatively.