bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastric electrical activity and gastric emptying in term and preterm newborns
Authors: Riezzo G. , Indrio F. , Montagna O. , Tripaldi C. , Laforgia N. , Chiloiro M. , Mautone A.
Published: March 2003

The aims of this study were to evaluate the gastric electrical activity and gastric emptying in preterm and term newborns and to assess the development of gastric motility by comparing newborns of different gestational ages. The cutaneous electrogastrography and the ultrasonographic study of the gastric emptying were performed before and after milk formula in three groups of infants: 12 preterm newborns with a gestational age of 28–32 weeks, 11 preterm newborns with a gestational age of 32–36 weeks, and 10 full‐term newborns with a gestational age of 36–40 weeks. All recording sessions were performed 1 week after infants had reached full enteral feeding. The percentage of normal slow waves was similar in the three groups but it was not predominant compared to tachygastria in the earliest premature infants (59.3% (12.7–92.3) vs. 29.6% (3.7–78.8); P < 0.05). In addition, a progressive increase in the normal slow wave percentage (59.3% (17.4–87.4), 60.9% (38.1–89.7), 77.8% (66.4–84.8); P < 0.05) was observed as gestation advanced. As regards gastric emptying parameters, the antral area was greater and T½ was longer in the preterm newborns of 28–32 weeks than preterm newborns of 32–36 weeks and full‐term newborns (fasting antral area: 0.96 cm2 (0.6–1.5), 0.63 cm2 (0.4–1.2), 0.55 cm2 (0.1–0.9) respectively, P < 0.05; T½: 83.4 min (76.0–108.5), 70 min (57.5–89.5) and 71.8 min (54.9–81.2), respectively P < 0.05). The comparisons of gastric emptying curves made among the three groups showed a reduced antral dilatation in preterm newborns of 28–32 weeks compared to full‐term newborns at 30 and 60 min after a meal. In conclusion, although enteral feeding is important for the development process of gastrointestinal motility, gastric electrical activity and gastric emptying show an intrinsic maturation depending on the gestational age.
The effect of mechanoreceptor stimulation of the laryngopharynx on the oesophago‐gastric junction
Authors: Noordzij  , Mittal  , Arora  , Pehlivanov  , Liu  , Reibel  , Levine
Published: March 2003

Stimulation of the pharynx by injection of minute amounts of water induces prolonged period of lower oesophageal sphincter (LOS) relaxation and augmentation of the crural diaphragm (CD) contraction. The purpose of this study was to determine the effects of stimulating mechano‐receptors at the laryngopharynx on the LOS and CD by using an air pulse stimulation device. Air pulses were delivered via the internal channel of a flexible endoscope. Oesophageal, LOS, and CD pressures; CD electromyogram; and oesophageal pH 5 cm above the LOS were recorded in nine healthy subjects. Stimulation of the laryngopharynx induced LOS relaxation in the absence of swallow and oesophageal peristalsis. The stimulation of epiglottis and arytenoid produced higher incidence of LOS relaxation compared to the base of tongue. The magnitude of LOS relaxation differed significantly between the three anatomical sites, with greater relaxation occurring at the epiglottis and arytenoid compared with the base of the tongue. None of the LOS relaxations induced by laryngeal stimulation resulted in inhibition of the CD or gastroesophageal reflux. We conclude that stimulation of the laryngopharyngeal mechanoreceptors induces LOS but not CD relaxation. The LOS relaxation induced by laryngopharyngeal stimulation is not accompanied by acid reflux in fasting state.
Increased mast cells in the irritable bowel syndrome
Authors: O’Sullivan  , Clayton  , Breslin  , Harman  , Bountra  , Mclaren  , O’Morain
Published: March 2003

Mast cells (MC) release potent mediators which alter enteric nerve and smooth muscle function and may play a role in the pathogenesis of the irritable bowel syndrome (IBS). The aim of this study was to determine if MC were increased in the colon of IBS patients compared to controls. Biopsy specimens were obtained from the caecum, ascending colon, descending colon and rectum of 28 patients: 14 IBS (Rome criteria); seven normal; and seven inflammatory controls. Tissue was stained immunohistochemically using a monoclonal mouse antibody for human mast cell tryptase (AA1). Tissue area occupied by tryptase‐positive MC (volume density of mast cells) was quantified by image analysis. The number of plasma cells, lymphocytes, eosinophils, neutrophils and macrophages were each graded semiquantitatively (0–4) in haematoxylin and eosin stained sections. Mast cell volume density was significantly (P < 0.05) higher in IBS (0.91 ± 0.18; CI 0.79; 1.0) than normal controls (0.55 ± 0.14; CI 0.40; 0.69) in the caecum but not at other sites. Apart from MC, there was no evidence of increased cellular infiltrate in the IBS group. MC were significantly increased in the caecum of IBS patients compared to controls. The multiple effects of the intestinal mast cell alone, or as a participant of a persistent inflammatory response, may be fundamental to the pathogenesis of IBS.
Histamine in the control of porcine and human sphincter of Oddi activity
Authors: Sand J. , Arvola P. , Pörsti I. , Jäntti V. , Oja O. S. , Baer G. , Nordback I.
Published: March 2003

Histamine decreases sphincter of Oddi (SO) contractility in vivo in opossum, but increases contractility in vitro in guinea‐pig. In resistor‐like SO, such as in pig and man, the histamine effect is poorly known. We investigated the effect of histamine on pig SO in vivo and in vitro and on human SO in vitro. Perfusion manometry catheter and two silver electrodes for simultaneous pressure and electromyography registration were inserted into the SO transduodenally by laparotomy in six anaesthetized pigs weighing for 25–28 kg. Histamine (5–10 μg kg–1) was infused intra‐arterially (i.a.) into the pancreaticoduodenal artery with and without diphenhydramine (75 μg kg–1) i.a. premedication. Acetylcholine (4 μg kg–1) i.a., a potent SO stimulator, was used as positive control. After these experiments, the SO was removed and, together with seven human SO from Whipple specimens, were cut into 1.0–1.5 mm thick transverse sections (rings). The rings were placed between two hooks in oxygenated organ bath solution at 37 °C. The SO contraction force was measured with isometric force–displacement transducers and registered on a polygraph. SO rings were incubated with histamine (10–100 μmol L–1) and acetylcholine (100 μmol L–1) with or without diphenhydramine (10 μmol L–1), cimetidine (10 μmol L–1), or atropine (1 μmol L–1). Acetylcholine induced huge electrical bursts, and basal SO pressure increased by 20 ± 10 mmHg. Histamine (10 μg kg–1) induced strong SO contraction and the SO remained oedematous for over 10 min. Histamine (5 μg kg–1) resulted in electromyographic burst activity with phasic SO contractions and increase in basal SO pressure by 34 ± 19 mmHg for over 15 min. Diphenhydramine did not alter acetylcholine‐induced SO motility, but significantly decreased histamine‐induced contractions and almost abolished electrical activity. In vitro, acetylcholine induced SO contractions in pig (335 ± 111 mg) and in man (323 ± 54 mg). Histamine did not change SO tone in man, but in pig it induced dose‐dependent contractions in the same way as acetylcholine. These contractions could be inhibited by diphenhydramine, but not by cimetidine or atropine. We conclude that histamine has a stimulatory effect, mediated by H1‐receptor, on the pig SO motility. The SO response to histamine is different in adult humans from that observed in young pigs.
Intestinal and colonic motor alterations associated with irradiation‐induced diarrhoea in rats
Authors: Picard C. , Wysocki J. , Fioramonti J. , Griffiths N. M.
Published: March 2003

Localized application of ionizing radiation to the gastrointestinal tract frequently elicits responses, which include diarrhoea. The origin of this symptom is not clear but has been attributed to loss of epithelial integrity, together with alterations in motility and increased secretion. The purpose of this study was to examine whether a 10 Gy abdominal gamma irradiation leads to an inflammatory reaction, and to compare intestinal and colonic motility in controls and abdominally irradiated rats 1, 3 and 7 days after irradiation, using an electromyographic technique. The motility parameters analysed were the frequency and velocity of propagation of migrating myoelectric complexes (MMC) in the jejunum and colonic spike activity (long spike bursts; LSB) per 10 min in fasted rats. The MMC frequency was significantly reduced on days 1 and 7 after irradiation and the MMC pattern was markedly disrupted on day 3. The frequency of colonic LSB was significantly reduced on days 1, 3 and 7. Mouth to anus transit was significantly accelerated on day 3 only and diarrhoea was observed at this time. Myeloperoxidase activity in the jejunum and colon was also increased on this day only. It is concluded that irradiation‐induced diarrhoea occurs contemporaneously with disruption of MMC in the small intestine.
Haem oxygenase in enteric nervous system of human stomach and jejunum and co‐localization with nitric oxide synthase
Authors: Miller S. M. , Reed Darcy , Sarr M. G. , Farrugia G. , Szurszewski J. H.
Published: March 2003

Recent evidence suggests that carbon monoxide (CO) may be a neurotransmitter, similar to nitric oxide (NO) in the enteric nervous system. The distribution of haem oxygenase (HO), the biosynthetic enzyme for CO, has been determined in the enteric nervous system of animals, but little is known about the distribution of HO in human gastrointestinal tract. The present study investigated the expression of HO and its colocalization with NO synthase (NOS), the biosynthetic enzyme for NO, in human antrum and jejunum. HO isoforms were identified using immunohistochemistry and NOS was identified by immunohistochemistry or NADPH‐d histochemistry. HO‐2 immunoreactive (IR) cell bodies in enteric ganglia and nerve fibres in longitudinal and circular muscle were found in both antrum and jejunum. Co‐localization of HO‐2 and NOS was about 40% in HO‐2 containing cell bodies of myenteric ganglia and only 10% or less in cell bodies of submucous ganglia. HO‐1 immunoreactivity was not detected in antrum or jejunum. The results suggest that CO is produced in human enteric ganglion neurones and indicate a possible role of CO as a neurotransmitter and possible interaction between HO and NOS pathways in inhibitory neurotransmission in the human gastrointestinal tract.
ATP and 5‐HT are the principal neurotransmitters in the descending excitatory reflex pathway of the guinea‐pig ileum
Authors: Monro R. L. , Bertrand P. P. , Bornstein J. C.
Published: March 2003

Abstract
 
Neurotransmission underlying descending excitatory reflexes evoked by distension was studied in opened segments of guinea‐pig ileum and compared with peristalsis in intact segments. The opened segments were distended by inflating a balloon against the serosa at the oral end and changes in muscle length recorded from the anal end. Distension elicited contractions in both circular (CM) and longitudinal (LM) muscle layers. Granisetron, a 5‐HT3receptor antagonist (10 nmol L−1to 1 µmol L−1) reduced CM contractions (24% control), without affecting the LM. The P2 receptor antagonist, pyridoxal phosphate‐6‐azopheyl‐2′,4′‐disulphonic acid (PPADS; 10 µmol L−1), reduced CM contractions to 31% and LM contractions to 39%. Hexamethonium (500 µmol L−1) enhanced LM contractions, but had no effect on CM contractions. Granisetron (1 µmol L−1) had no significant effect on the threshold for peristaltic contractions in a modified Trendelenburg preparation, but decreased the decay time of these contractions by 37%. PPADS (10 µmol L−1) had no significant effect in this preparation. Thus, the descending excitatory pathways to CM and LM can be distinguished pharmacologically; the former depend on 5‐HT3and P2 ATP receptors, the latter are independent of 5‐HT3receptors. Nicotinic receptors may have little part in either pathway. These properties differ from conventional peristaltic reflexes, which are effectively abolished by nicotinic blockade.
Modulation of human swallowing behaviour by thermal and chemical stimulation in health and after brain injury
Authors: Hamdy S. , Jilani S. , Price V. , Parker C. , Hall N. , Power M.
Published: March 2003

Abstract Few data support thermal or chemical stimulation as therapy for neurogenic dysphagia. Our aims were to explore the behavioural effects of thermal (cold) and chemical (citrus) modalities on water swallowing in health (n = 65, mean age 45 years, 44 females) and acute stroke (n = 22, mean age 67 years, eight females). Multiple randomized timed 50‐mL swallowing tests were performed for each of four water conditions: (a) room temperature (RT), (b) cold (CD), (c) citrus (CT) and (d) combined cold and citrus (CD + CT). The inter‐swallow interval (ISI), swallowing volume velocity (speed), and volume per swallow (capacity) were measured. In health, compared to RT, only CD + CT slowed the speed (12.3 ± 0.5 vs 10.3 ± 0.5 mL s−1, P < 0.03) and decreased the capacity (16.4 ± 0.9 vs 14.6 ± 0.7 mL per swallow, P < 0.02) of swallowing. ISI was unaffected, except by CD + CT in healthy young subjects (<60 years) where it was reduced (1.44 ± 0.02 vs 1.30 ± 0.02 s, P < 0.02). Despite smaller volumes ingested by stroke patients, CD + CT, compared to RT, again slowed both the speed (3.8 ± 0.4 vs 4.5 ± 0.5 mL s−1, P < 0.03) and capacity (7.6 ± 0.7 vs 8.5 ± 0.7 mL per swallow, P < 0.03) of swallowing but had no effect on ISI. We conclude that combined thermal and chemical modification of water consistently alters swallowing behaviour in health and after cerebral injury. These findings have relevance in the management of neurogenic swallowing problems.
Amyloid β protein (Aβ) deposition in dementia with Lewy bodies: predominance of Aβ42(43) and paucity of Aβ40 compared with sporadic Alzheimer’s disease
Authors: Mann  , Brown  , Owen  , Baba  , Iwatsubo
Published: March 2003

Amyloid β protein (Aβ) deposition was investigated by quantitative immunohistochemistry in 13 cases of dementia with Lewy bodies (DLB) and compared with that in a series of age, gender and ApoE genotype matched cases of Alzheimer’s disease (AD). In DLB the predominant Aβ peptide species deposited was Aβ42(43) and this was similar in amount to that in AD. By contrast, Aβ40 deposition was sparse in DLB and was lower than that in AD as was the total Aβ (Aβ40+Aβ42(43) ) deposition. These data reinforce the viewpoint that in all disorders in which Aβ deposition is characteristic, the initial and predominant peptide species deposited is the longer form, Aβ42(43) . The density of Lewy bodies (LB) in DLB was unrelated to the extent of Aβ deposition, although those cases possessing one or more copies of the apolipoprotein E E4 allele had a higher LB density than those without an E4 allele. This suggests that the apolipoprotein E E4 isoform might facilitate, though not necessarily trigger, the formation of LB in susceptible individuals.
Histopathological responses in the CNS following inoculation with a non‐neurovirulent mutant (1716) of herpes simplex virus type 1 (HSV 1): relevance for gene and cancer therapy
Authors: McKie  , Brown  , MacLean  , Graham
Published: March 2003

The RL1 gene of herpes simplex virus (HSV) encodes a polypeptide, ICP34.5 which is a specific virulence determinant. RL1 null mutants fail to replicate in both the PNS and CNS and are incapable of causing encephalitis. Additionally, RL1 null mutants have the capacity to replicate in actively dividing cells but fail to replicate in growth arrested or terminally differentiated cells. This selective replication phenotype has highlighted their use as both tumour killing agents and gene delivery vehicles particularly to the nervous system. Before their full potential can be assessed, however, it is necessary to determine the pathological and immune responses induced following direct intracerebral inoculation. Fourteen mice were injected in the left cerebral hemisphere with a high dose of the HSV‐1, RL1 null mutant 1716. At regular time intervals up to 28 days, the mice were killed and the distribution of virus antigen, histopathological changes and immune responses in the CNS determined by H & E staining and immunohistochemistry. Control mice were injected with either wild type HSV‐1 or buffer. At early times post‐ inoculation with 1716, there is a low grade meningoencephalitis with a limited inflammatory response. This is accompanied by virus antigen expression confined to the site of inoculation. By 28 days the CNS is histopathologically normal; virus antigen and immune responses are no longer detectable. These findings demonstrate that infection of the CNS by RL1 null mutants of HSV results in a finite, self‐limiting response and highlights their potential for therapeutic use.
The presence of FAC1 protein in Hirano bodies
Authors: Jordan‐Sciutto  , Dragich  , Walcott  , Bowser
Published: March 2003

We have previously reported that the FAC1 protein is contained in hippocampal structures that resemble Hirano bodies. Hirano bodies are cytoplasmic inclusions containing actin filaments that are numerous in the hippocampus of many Alzheimer’s disease patients. FAC1 is a developmentally regulated protein that is localized to the cytoplasm of neurons during development and is predominately a nuclear protein in adult brain. In hippocampal sections from non‐demented adults, Alzheimer’s disease, and dementia with Lewy bodies patients, Hirano bodies were immunolabelled with antibodies to the FAC1 protein. Confocal laser microscopy demonstrated the presence of actin in FAC1 labelled Hirano bodies, and ultrastructural analysis confirmed the presence of a lattice structure within FAC1 labelled Hirano bodies. Numerous FAC1 immunoreactive swollen dendrites were also present in the hippocampus of Alzheimer’s disease and dementia with Lewy bodies patients. Within any one case the total number of FAC1 positive swollen dendrites correlated with the total number of Hirano bodies, suggesting an association between the two structures. Thus, FAC1 protein is contained in Hirano bodies and swollen dendrites in the hippocampus of patients with Alzheimer’s disease and dementia with Lewy bodies.
Expression of amyloid precursor protein (β‐APP) in the neonatal brain following hypoxic ischaemic injury
Authors: Baiden‐Amissah  , Joashi  , Blumberg  , Mehmet  , Edwards  , Cox
Published: March 2003

Perinatal hypoxic ischaemic brain injury (HII) is a major cause of neonatal mortality and long‐term neurological morbidity. An understanding of the molecular events which follow HII may lead to novel treatments to improve the final outcome for affected infants. The β‐amyloid precursor protein (β‐APP) is a widely expressed transmembrane protein whose proposed functions include stabilization of neuronal calcium fluxes, inhibition of the clotting cascade and cell–cell or cell–matrix adhesion. Normally present at low levels in neurons its expression is induced as part of the acute response of the adult brain to HII. This study aimed to determine whether β‐APP is also part of the acute adaptive response of the infant brain to HII. Immunohistochemistry and Western blotting were used to assess cerebral β‐APP expression in 14‐day‐old rat pups subjected to unilateral HII, and in 10 term human infants, who died between 12 h and 16 months after severe perinatal HII. In the rat pups β‐APP expression was increased by 2 h post‐injury, peaked, fourfold above control levels, at 24 h and gradually declined over the following 4 days. Expression was induced bilaterally, but was greater on the side of injury. In the human infants, increased, predominantly neuronal expression of β‐APP, was detectable immunohistochemically within 24 h of injury and was greatest in those infants dying within 3 days. Expression was particularly strong in the areas showing histological evidence of injury, but was also seen in apparently undamaged areas. We conclude that β‐APP induction is part of the the acute adaptive response of the neonatal brain to HII.
A murine model of HIV encephalitis: xenotransplantation of HIV‐infected human neuroglia into SCID mouse brain
Authors: Sanders  , Mehta  , White  , Achim
Published: March 2003

The degree of neuronal damage in HIV encephalitis (HIVE) and the mechanisms leading to it are not known. Post‐mortem human studies provide limited information concerning pathogenesis, and there are few animal models of HIVE. We have developed a murine model of HIVE based on HIV‐infected human brain tissues grafted within the host CNS milieu. HIV‐infected blood‐derived macrophages were cocultured with and incorporated within second trimester human fetal brain neuroglia. Mixed neuronal‐glial aggregates were injected into the striatum of SCID mice where they survived for more than 6 months. Cellular proliferation and differentiation were determined by immunohistochemical staining for proliferating cell nuclear antigen and cellular markers. Synapse formation was seen by immunocytochemistry for synapsin and by electron microscopy. Virus was detected by immunohistochemical staining for HIV gp41. Based on the long‐term survival of human neuroglial xenografts containing HIV infected macrophages, we believe that this model will support the study of chronic HIV‐associated neurodegeneration and the testing of various CNS targeted therapeutic interventions.
Galectin‐3 and galectin‐3‐binding site expression in human adult astrocytic tumours and related angiogenesis
Authors: Gordower  , Decaestecker  , Kacem  , Lemmers  , Gusman  , Burchert  , Danguy  , Gabius  , Salmon  , Kiss  , Camby
Published: March 2003

Using computer‐assisted microscopy, the present work aimed to quantitatively characterize the level of the histochemically detectable expression of galectin‐3 and galectin‐3‐binding sites in sections of a series of 84 astrocytic tumours (including 22 grade II, 21 grade III and 41 grade IV specimens) and seven non‐tumoural specimens used as controls. The presence of galectin‐3 and reactive sites for this lectin were monitored by means of a specific polyclonal anti‐galectin‐3 antibody (aGal3) and biotinylated galectin‐3 (Gal3), respectively. The pattern of expression of galectin‐3‐binding sites is compared to the pattern of expression of laminin (a potential galectin‐3 ligand) revealed using a biotinylated anti‐laminin antibody (aLam). Three variables quantitatively characterizing histochemical staining reactions were evaluated by means of computer‐assisted microscopy for each of the 3 probes under study (aGal3, Gal3 and aLam). The labelling index (LI) is the percentage of tissue area specifically stained by a histochemical probe. The mean optical density (MOD) denotes staining intensity. The concentration heterogeneity (CH) feature expresses the concentrational spread of individual fields. The data obtained in the present study show that: (i) white matter of a non‐tumoural brain expresses galectin‐3 (and also galectin‐3‐binding sites); (ii) the level of galectin‐3 expression significantly decreases in the majority of tumour astrocytes from low to high grade astrocytic tumours; while (iii) some tumour cell clones expressing high amounts of galectin‐3 emerged with increasing levels of malignancy; and (iv) the level of accessible galectin‐3‐binding sites was apparently not heavily modified in the course of malignancy progression. In conclusion, the results obtained in the present study show that human astrocytic tumours are very heterogenous in their galectin‐3 levels of expression. If high levels of galectin‐3 determine the invasiveness potential of a tumour cell, then within a heterogenous tumour the presence of even a small, but actively proliferating number of tumour cell clones expressing high levels of galectin‐3 can be expected to lead to tumour invasiveness.
Mechanisms of damage to myelin and oligodendrocytes and their relevance to disease
Authors: Merrill  , Scolding
Published: March 2003

Oligodendrocytes synthesize and maintain myelin in the central nervous system (CNS). Damage may occur to these cells in a number of conditions, including infections, exposure to toxins, injury, degeneration, or autoimmune disease, arising both in the course of human disease and in experimental animal models of demyelination and dysmyelination; multiple sclerosis is the commonest human demyelinating disorder. Conventional classical accounts of the pathology of this and other myelin diseases have given great insights into their core features, but there remain considerable uncertainties concerning the timing, means and cause(s) of oligodendrocyte and myelin damage. At present, therapeutic efforts largely concentrate on immune manipulation and damage limitation, an approach that has produced only modest effects in multiple sclerosis. One reason for this must be the limited understanding of the mechanisms underlying cell damage – clearly, successful therapeutic strategies for preserving the oligodendrocyte‐myelin unit must depend on knowledge of how oligodendrocyte damage and death occurs.

In this review, mechanisms of oligodendrocyte and myelin damage are considered, and attempts made to relate them to disease processes, clinical and experimental. The hallmarks of different cell death processes are described, and oligodendrocyte‐myelin injury by cellular and soluble mediators is discussed, both in vitro and invivo. Recent developments concerning the pathological involvement of oligodendrocytes in neurodegenerative disease are summarized. Finally, these neuropathological and applied neurobiological observations are drawn together in the context of multiple sclerosis.
Synapse loss is greater in presenile than senile onset Alzheimer disease: implications for the cognitive reserve hypothesis
Authors: Bigio E. H. , Hynan L. S. , Sontag E. , Satumtira S. , White C. L.
Published: March 2003

In the past, ‘Alzheimer disease’ (AD) referred to pathologic AD with clinical onset of dementia in the presenium, while ‘senile dementia of the Alzheimer type’ (SDAT) referred to senile onset AD. Because AD appears clinically homogeneous regardless of age of onset, the two subtypes in more recent years have not been distinguished. Pathologic differences have been noted, but synapse loss has not previously been compared between the two groups. Hypothesizing that synapse loss would be greater in presenile onset than senile onset AD, we compared synapse loss, as well as Alzheimer pathology in presenile and senile onset AD, using an ELISA method to quantify synaptophysin. Synaptophysin was significantly lower in presenile than senile AD in right frontal and bilateral parietal lobes. Neuritic plaque counts were significantly higher in presenile than senile AD in bilateral frontal and parietal lobes. Semi‐quantitative evaluation of neurofibrillary tangles revealed significantly more tangles in bilateral frontal and parietal lobes in presenile than senile AD. Brain weight was significantly lower in presenile than senile AD. The differences in synapse loss and Alzheimer‐type pathology in presenile and senile onset AD support the hypothesis that ‘cognitive reserve’ protects the human brain from neurodegenerative disease.
Early accumulation of p62 in neurofibrillary tangles in Alzheimer's disease: possible role in tangle formation
Authors: Kuusisto E. , Salminen A. , Alafuzoff I.
Published: March 2003

Neurofibrillary tangles (NFTs) and neuritic plaques (NPs) are two major histopathological lesions in Alzheimer's disease (AD). Although their aetiological relationship is unclear, both NFTs and dystrophic neurites of NPs display immunoreactivity for ubiquitin. This suggests that dysfunction in ubiquitin‐mediated proteolysis and the resulting accumulation of ubiquitin‐conjugated proteins may contribute to the origination of dystrophic neurites and NFTs. We recently discovered a novel constituent of neuropathological protein aggregates, ubiquitin‐binding protein p62, with evidence that the accumulation of ubiquitin‐conjugated proteins and p62 into cytoplasmic inclusions might be interconnected. In the present work we examined in detail the role of p62 in AD‐type pathology, i.e. NFTs, NPs and neuropil threads. Using immunohistochemistry for p62, ubiquitin and hyperphosphorylated tau, we analysed parietal cortical samples of 15 clinicopathologically verified AD cases and nine nondemented aged subjects with abundant NPs. We found that p62 immunoreactivity appears early during neurofibrillary pathogenesis and is invariably and stably present in NFTs. In contrast, p62 was absent or barely detectable in neuropil threads. Furthermore, NP‐associated dystrophic neurites were generally devoid of p62, regardless of their content of hyperphosphorylated tau and/or ubiquitin. The results suggest that early involvement of p62 might be critical in the aggregation of hyperphosphorylated tau into perikaryal aggregates, i.e. NFTs.
The role of cytochrome c oxidase deficient hippocampal neurones in Alzheimer's disease
Authors: Cottrell D. A. , Borthwick G. M. , Johnson M. A. , Ince P. G. , Turnbull D. M.
Published: March 2003

Defects of mitochondrial function have been proposed as a potential mechanism in the development and pathogenesis of Alzheimer's disease (AD) and neuronal apoptosis. Mitochondrial enzyme‐deficient pyramidal neurones are found in greater quantities in the hippocampus of AD patients than in age‐matched controls. The presence of these neurones indicates that high levels of mutant mtDNA (mitochondrial DNA), sufficient to cause a biochemical deficiency within individual neurones, occur more frequently in AD than in normal ageing. This study analyses the relationship of cytochrome c oxidase (COX)‐deficient neurones with the neuropathological markers of AD, neurofibrillary tangles (NFTs) and amyloid plaques, as well as markers of neuronal apoptosis known to occur in AD brains. Frozen sections of hippocampi from three AD patients were used to directly colocalize in situ the presence of histochemically COX‐deficient neurones with immunohistology for the classical neuropathological markers of AD, tau and β‐amyloid. In addition, we also directly colocalized these mitochondrial‐enzyme deficient neurones using terminal deoxynucleotidyl transferase‐mediated dUTP nick end labelling and cleaved caspase‐3. The distribution of amyloid plaques is anatomically distinct from the COX‐deficient hippocampal pyramidal neurones and the neurones that contained NFTs or apoptotic labelling were always COX‐positive. COX‐deficient, succinate dehydrogenase‐positive hippocampal neurones indicative of high mtDNA mutation load do not appear to be prone to apoptosis or to directly participate in the over production of tau or β‐amyloid. Biochemically significant mitochondrial defects do occur in AD and are likely to contribute to the overall central nervous system dysfunction in impairing neuronal function and possibly causing neurodegeneration via mechanisms other than apoptosis.
Accumulation of immunoglobulin across the ‘blood–nerve barrier’ in spinal roots in adoptive transfer experimental autoimmune neuritis
Authors: Hadden R. D. M. , Gregson N. A. , Gold R. , Smith K. J. , Hughes R. A. C.
Published: March 2003

At the onset of Guillain–Barré syndrome, disruption of diffusion barriers, such as the blood–nerve barrier, probably increases the exposure of spinal roots and peripheral nerves to macromolecules, some of which might be pathogenic. As a measure of such disruption, we measured the accumulation in the endoneurium of spinal roots and sciatic nerve of systemically administered 125I‐labelled immunoglobulin in adoptive transfer experimental autoimmune neuritis (AT‐EAN) in the rat. AT‐EAN is a model of Guillain–Barré syndrome, induced by injection of activated T lymphocytes sensitized to myelin P2 protein. Immunoglobulin accumulation was expressed as counts/min/mg in fixative‐perfused roots as a percentage of that in serum, measured 24 h after intraperitoneal injection of 0.1 µCi 125I‐labelled immunoglobulin. Immunoglobulin accumulation in the roots of normal rats was 3 ± 1% (mean ± SE), but this first increased 3½ days after cell injection, peaked at 22 ± 2% on day 4½, and declined to normal by day 8. T lymphocytes and polymorphonuclear leucocytes first appeared within the endoneurium at day 3½, and macrophages and a few erythrocytes at day 4. Neurological deficit appeared on day 4 and was maximal on day 6. Demyelination and axonal degeneration began at day 5. The first abnormality detected in AT‐EAN was a rapid increase in the passage of immunoglobulin into spinal roots, together with endoneurial infiltration of T lymphocytes and polymorphonuclear leucocytes. Accumulation of immunoglobulin was maximal during the worsening of neurological deficit, and declined rapidly before the onset of neurological recovery.
An overlooked population of the beira antelope Dorcatragus megalotis in Djibouti
Authors: Künzel Th. , Künzel S.
Published: March 2003

The beira antelope Dorcatragus megalotis, which is listed as possibly extinct in Djibouti in the 1996 IUCN Red List, was observed there by the authors in 1993/94. The authors discuss its status in the country and the action needed for its conservation.
Status survey of slender loris Loris tardigradus lydekkerianus in Dindigul, Tamil Nadu, India
Authors: Singh Mewa , Lindburg Donald G. , Udhayan A. , Kumar M. Anand , Kumara H. N.
Published: March 2003

A survey of the slender loris Loris tardigradus, a Vulnerable primate, was carried out in the Dindigul Forests of Tamil Nadu, India, in 1996 in order to assess prevalence. Lorises were found in high densities in the open Euphorbia scrub forests and in crop lands nearby. Although most often seen in bushes and Acacia trees, the species uses a wide variety of vegetation and substrates. Individuals were found mostly at an altitude of 300–500 m. Body measurements taken on sample animals revealed that the population belongs to the subspecies L. t. lydekkerianus. Conservation measures for the species in this region include additional surveys and evaluation of prospects for establishing a slender loris sanctuary.
Wildlife rescues—the case of the Petit Saut hydroelectric dam in French Guiana
Authors: Vié Jean-Christophe
Published: March 2003

Many wildlife rescues have been carried out over the past few decades but most were not documented and were controversial. However, such operations can be useful, providing risks are evaluated and elementary guidelines are followed. In addition to saving lives and being desirable from an ethical point of view, such operations can be very valuable for both biological research and conservation, and are certainly preferable than the alternative: to do nothing. Previous rescues are reviewed and the operation conducted in French Guiana during the filling of the Petit Saut reservoir is described. Objectives, methods, results and financial aspects are discussed. Around 5500 mammals and reptiles were captured, sampled and translocated to a protected area. The successful results of the translocation, the large amount of original data obtained, the interest shown by scientists in our samples and the subsequent new conservation impetus that appeared in the government corroborate our initial conviction that the operation was worthwhile.
Local community involvement in conservation—the use of mini-guides in a programme for sea turtles in Brazil
Authors: Vieitas Claudia F. , Lopez Gustave G. , Marcovaldi Maria A.
Published: March 2003

The Brazilian Sea Turtle Conservation Programme (TAMAR) was established in 1980 to protect sea turtles in Brazil and to re-establish their natural life cycle, which had been disrupted by humans. The programme is based on grassroots involvement by the coastal communities, and provides jobs and generates alternative sources of income. Within this framework, the mini-guides programme was created. It consists of a summer training course in which local children between 8 and 13 years old learn basic information about marine ecosystems and sea turtles, strategies to promote their conservation, and skills to interact effectively with tourists. After the course, children are given onsite experience by working as interns at the TAMAR visitor centre at Praia do Forte, on schedules designed to avoid conflicts with their studies at school. The children work closely with tourists, informing them about sea turtles and TAMAR's work; they also help the biologists in field activities. In this way, they enhance their own awareness, and by extension their families' and the community's concern about environmental conservation. Their involvement provides them not only with valuable skills, but also an extra source of income, thereby providing economic benefits to their families. The success of this programme is indicated by the excellent approval ratings given by the tourists visiting the area.
The conservation status of the Chinese alligator
Authors: Thorbjarnarson John , Xiaoming Wang
Published: March 2003

The Chinese alligator Alligator sinensis is one of the world's most endangered reptiles. At one time widespread throughout much of the lower Yangzi River basin, the remaining wild individuals are now restricted to a small area in southern Anhui Province and perhaps in adjacent Zhejiang Province. Population estimates conducted in the 1980s suggested that only 500–735 wild individuals remained at that time. Current figures suggest that the wild population is c. 400 individuals and continues to decline. The principal factor contributing to historic population decline has been habitat loss, but deliberate killing of alligators and the heavy use of pesticides have also had significant negative effects. The current conservation programme in Anhui Province is based on captive breeding and the establishment of a reserve for small groups of wild alligators. However, the inferred recent decline in the size of the wild population suggests that the reserve design is inadequate for the long-term survival of alligators. Programmes to survey the status of the remaining wild populations and evaluate the feasibility of establishing new wild populations by reintroducing captive-bred animals are currently being developed.
Conserving the African wild dog Lycaon pictus. I. Diagnosing and treating causes of decline
Authors: Woodroffe Rosie , Ginsberg Joshua R.
Published: March 2003

The African wild dog Lycaon pictus has declined dramatically over the past 30 years. Formerly distributed throughout sub-Saharan Africa, today c. 5000 wild dogs remain in total, mostly in southern and eastern Africa. Wild dogs' decline reflects the expansion of human populations and the associated fragmentation of habitat available to wildlife. Because wild dogs live at very low densities, even ‘fragments’ covering thousands of square kilometres may not support viable populations. Furthermore, packs often range beyond the borders of reserves, so even nominally protected populations are often subject to persecution, road accidents, snaring and disease contracted from domestic dogs. Such edge effects mean that reserves smaller than c. 10,000 sq km will provide only incomplete protection. The highest priority for wild dog conservation, therefore, is to maintain and promote the contiguity of areas available to wildlife. Establishing cross-border parks and buffer zones, and encouraging game ranching on reserve borders, will all be beneficial. In smaller areas, protecting wild dogs requires that edge effects be mitigated by: (i) working with local farmers to limit persecution; (ii) controlling snaring; (iii) routing roads carrying high-speed traffic away from wildlife areas; and (iv) minimizing contact between wildlife and domestic dogs. Most of these measures will also benefit other wildlife.
African elephants and humans in conflict: the outlook for co-existence
Authors: Hoare Richard
Published: March 2003

The future persistence of African elephants over the 80 per cent of the species's range that remains outside protected areas is increasingly uncertain in many parts of the continent. Conflict between elephants and agriculturalists is already widespread and can lead to displacement or elimination of elephants, causing a further decline in their range and numbers. ‘Protectionist’ conservation groups have recently attempted to play down the importance of human–elephant conflict, contending that it has been greatly exaggerated by those advocating sustainable use of wildlife. The future of elephants in ecosystems over much of the continent will depend largely upon the attitudes and activities of humans. The realities of survival faced by rural Africans may mean that little attention will be paid to a debate taking place on conservation philosophy in the developed world. Therefore, the IUCN African Elephant Specialist Group (AfESG) is investigating how human land use can be integrated with the needs of elephant populations in Africa's biogeographical regions. Findings from these studies will be used in attempts to benefit elephant conservation and management in the 37 African elephant range states.
Bird and mammal conservation in Gaoligongshan Region and Jingdong County, Yunnan, China: patterns of species richness and nature reserves
Authors: Lan Daoying , Dunbar Robin
Published: March 2003

Elevational and latitudinal patterns of species richness for birds and mammals were compared with human population density in relation to nature reserve designation in two areas of Yunnan Province, China. Results suggest that species richness is not the same for the two areas. In Gaoligongshan Region, species richness is inversely correlated with elevation and altitude, while reserve designation is positively correlated with elevation and latitude. In Jingdong County, reserve designations are positively correlated with elevation, but species richness shows no clear trends. In general, the present situation is strongly influenced by human activities. It appears that reserve designation is mismatched with species richness in Gaoligongshan Region, while there is a better fit between the two in Jingdong County. In both areas, however, it appeared that reserves were located primarily in order to reduce conflict with humans rather than to maximize conservation of biodiversity, probably because humans were responsible for forest—especially primary forest—destruction and degradation in the low-lying areas.
A population survey of the estuarine crocodile in the Ayeyarwady Delta, Myanmar
Authors: Thorbjarnarson John , Platt Steven G. , Khaing U. Saw Tun
Published: March 2003

The estuarine crocodile Crocodylus porosus was formerly abundant in coastal regions of Myanmar, but is now known principally from the lower Ayeyarwady Delta. We conducted a survey during January 1999 to assess quantitatively the status of crocodile populations in protected areas of the lower delta. Spotlight counts were conducted along 275.4 km of waterways. Sixty-one crocodiles (50 juveniles, 4 subadults, 2 adults and 5 eyeshines) were observed in the Meinmahla Kyun Wildlife Sanctuary (MKWS), and the total population was estimated to be less than 100. The Kadônkani and Pyindaye Reserved Forests (RF) apparently no longer support viable populations. Although crocodiles remain critically endangered in the region, a comparison with survey data from 1980 suggests localized recovery is occurring in MKWS. Population declines are attributed to a combination of commercial skin hunting, habitat loss, drowning in fishing nets and over-collection of living animals to supply crocodile farms. A programme of law enforcement, habitat protection and head-starting juveniles is necessary to ensure the continued survival of estuarine crocodiles in the Ayeyarwady Delta.
Status of a reintroduced population of mountain gazelles Gazella gazella in central Arabia: management lessons from an aridland reintroduction
Authors: Dunham Kevin M.
Published: March 2003

Mountain gazelles were reintroduced to central Arabia during 1991–95. Hawtah reserve was searched for gazelles during the 1998–99 winter. Gazelles were seen in one wadi system and their signs were found in several others and on the plateau. Sightings were used to calculate the minimum number of gazelles in the Matham wadi system, which previously held most of the population. During October–November 1998, the minimum number was 64 per cent less than 4 years earlier. Frequent observation of recent signs in areas where no gazelles were seen suggested that daytime sightings alone were no longer adequate for monitoring this population. The decline in the number of gazelles seen, an increase in their flight distance and an apparent change in their activity patterns were consistent with the rangers' claim that poaching had commonly occurred. Poaching started after reserve management built, without adequate consultation, a new fence that was intended to bar local people from part of the reserve. Management lessons include the need for the following: continued monitoring of reintroduced populations after the initial postrelease phase; long-term dialogue with local people; effective law enforcement; and the management of aridland domestic livestock in ways that prevent inter specific competition for food causing the elimination of wild ungulates.
Is there a legal obligation to reintroduce animal species into their former habitats?
Authors: Rees P. A.
Published: March 2003

Species reintroduction programmes are an important feature of global conservation efforts. There is evidence within the texts of some international and European laws of legal obligations to reintroduce species to their former habitats. However, these obligations are inconsistent between legal instruments, and it is not at all clear exactly what it is they are legislating to recreate. In particular, definitions of native species are either absent from the law or unclear, especially in an historical context. Attempts to reintroduce some predators have been met with legal challenges, and so it is essential that conservation authorities have a clear mission in their reintroduction activities and that this mission is reflected in their national law. Successful reintroductions will be achieved only with public support, and this is more likely where clear objectives have been established after public consultation. Conservation authorities undertaking reintroduction projects should use the legal system and the international commitments made by their governments to validate their efforts.
Distribution and status of the Apennine hare Lepus corsicanus in continental Italy and Sicily
Authors: Angelici Francesco M. , Luiselli Luca
Published: March 2003

The current distribution of Lepus corsicanus (recently considered to be a distinct species from L. europaeus) in peninsular Italy and Sicily is presented in this paper. Our data suggest that L. corsicanus is declining markedly in mainland Italy, and perhaps also in Sicily, and that it should be categorised as Endangered on the IUCN Red List. Conservation recommendations for this species are presented.