Chronic nicotine exposure stimulates biliary growth and fibrosis in normal rats

BackgroundEpidemiological studies have indicated smoking to be a risk factor for the progression of liver diseases. Nicotine is the chief addictive substance in cigarette smoke and has powerful biological properties throughout the body. Nicotine has been implicated in a number of disease processes, including increased cell proliferation and fibrosis in several organ systems.AimsThe aim of this study was to evaluate the effects of chronic administration of nicotine on biliary proliferation and fibrosis in normal rats.MethodsIn vivo, rats were treated with nicotine by osmotic minipumps for two weeks. Proliferation, α7-nicotinic receptor and profibrotic expression were evaluated in liver tissue, cholangiocytes and a polarized cholangiocyte cell line (normal rat intrahepatic cholangiocyte). Nicotine-dependent activation of the Ca²⁺/IP₃/ERK 1/2 intracellular signalling pathway was also evaluated in normal rat intrahepatic cholangiocyte.ResultsCholangiocytes express α7-nicotinic receptor. Chronic administration of nicotine to normal rats stimulated biliary proliferation and profibrotic gene and protein expression such as alpha-smooth muscle actin and fibronectin 1. Activation of α7-nicotinic receptor stimulated Ca²⁺/ERK1/2-dependent cholangiocyte proliferation.ConclusionChronic exposure to nicotine contributes to biliary fibrosis by activation of cholangiocyte proliferation and expression of profibrotic genes. Modulation of α7-nicotinic receptor signalling axis may be useful for the management of biliary proliferation and fibrosis during cholangiopathies.     

Distinct Membrane Effects of Spinal Nerve Ligation on Injured and Adjacent Dorsal Root Ganglion Neurons in Rats

Background: Painful peripheral nerve injury results in disordered sensory neuron function that contributes to the pathogenesis of neuropathic pain. However, the relative roles of neurons with transected axons versus intact adjacent neurons have not been resolved. An essential first step is identification of electrophysiologic changes in these two neuronal populations after partial nerve damage.

Methods: Twenty days after spinal nerve ligation (SNL), intracellular recordings were obtained from axotomized fifth lumbar (L5) dorsal root ganglion neurons and adjacent, intact L4 neurons, as well as from control neurons and others subjected to sham-SNL surgery.

Results: Pronounced electrophysiologic changes were seen only in L5 neurons after SNL. Both A[alpha]/[beta] and A[delta] neuron types showed increased action potential duration, decreased afterhyperpolarization amplitude and duration, and decreased current threshold for action potential initiation. A[alpha]/[beta] neurons showed resting membrane potential depolarization, and increased repetitive firing during sustained depolarization developed in A[delta] neurons. The afterhyperpolarization duration in neurons with C fibers shortened after axotomy. In contrast to the axotomized L5 neurons, neighboring L4 neurons showed no changes in action potential duration, afterhyperpolarization dimensions, or excitability after SNL. Depolarization rate (dV/dt) increased after SNL in L4 A[alpha]/[beta] and A[delta] neurons but decreased in L5 neurons. Time-dependent rectification during hyperpolarizing current injection (sag) was greater after SNL in A[alpha]/[beta] L4 neurons compared with L5. Sham-SNL surgery produced only a decreased input resistance in A[alpha]/[beta] neurons and a decreased conduction velocity in medium-sized cells. In the L5 ganglion after axotomy, a novel set of neurons, consisting of 24% of the myelinated population, exhibited long action potential durations despite myelinated neuron conduction velocities, particularly depolarized resting membrane potential, low depolarization rate, and absence of sag.     

Migration and health in the European Union

The paper gives a brief overview of a wide spectrum of health issues and problems, ranging from communicable disease to mental health and family formation, which affect migrants and host countries.     

The effects of Ipomoea carnea on goats and sheep

The clinical signs and lesions of Nubian goats and Desert sheep orally dosed with fresh and dry leaves and stems of Ipomoea carnea at 2.5, 5 and 10 g/kg/day were studied. The signs of Ipomoea poisoning were inappetence, depression, weakness of the hind limbs, dyspnea, staggering, and pallor of the visible mucous membranes. The main lesions were focal necrosis and fatty vacuolation of centrilobular hepatocytes, accumulation of fibroblasts in hepatic portal tracts, degeneration or necrosis of the cells of the renal proximal convoluted tubules, hemorrhage in renal cortices, in renal medullas and in cardiac muscle fibers, focal pulmonary edema, and emphysema and straw-colored fluid in serous cavities. Increased serum aspartate amino transferase and ammonia concentrations, and decreased concentrations of total protein, calcium and magnesium in the serum of Ipomoea-poisoned animals were detected. Hematological changes indicated the development of normocytic normochromic anaemia.     

Dissociation between in vitro and in vivo epileptogenicity in a rat model of cortical dysplasia.

OBJECTIVE: Malformations of cortical development are frequent causes of human refractory epilepsy. The freeze-lesion model in rats shows histopathological features similar to those found in human polymicrogyria. Previous studies reported in vitro hyperexcitability in this model, but in vivo epileptogenicity has not been confirmed. METHODS: Neocortical freeze lesions were induced in Sprague-Dawley rat pups (n = 10) on postnatal day 0 or 1 (P0/P1). Sham-operated animals served as controls (n = 10). On P60, animals were implanted with epidural electrodes for long-term video-EEG monitoring (4 weeks). The threshold for pentylenetetrazol-induced seizures was determined. Animals were sacrificed and brain sections processed for histological staining and in vitro electrophysiological recordings. Epileptiform field potential repetition rate, amplitude and integral were compared between slices containing a cortical freeze lesion, and slices from sham-operated rats. RESULTS: No interictal spikes and no electrographic or clinical seizures occurred in either group. The median threshold for pentylenetetrazol-induced seizures was 60 mg/kg for lesioned, and 45 mg/kg for control animals (difference not significant). No spontaneous epileptiform field potentials were recorded from either freeze-lesion or control slices bathed in normal, artificial cerebrospinal fluid (ACSF). Upon omission of Mg(2+) from the bath, epileptiform field potentials were elicited that showed a significantly higher burst integral in the freeze lesion slices compared to control slices. CONCLUSION: Neocortical freeze lesions induced in newborn rat pups show histological characteristics reminiscent of human cortical dysplasia. Brain slices containing neocortical freeze lesions display hyperexcitability in vitro, but the same lesion does not appear to show spontaneous epileptogenicity in vivo.     

Role of mitotic, pro-apoptotic and anti-apoptotic factors in human kidney development

The expression pattern of mitotic Ki-67 and anti-apoptotic bcl-2 proteins, as well as apoptotic caspase-3 and p53 proteins, were investigated in the human mesonephros and metanephros of 5–9 week-old human conceptuses. Apoptotic cells were additionally detected using the terminal deoxynucleotidyl transferase (TdT) nick-end labelling (TUNEL) method. Between the 5th and 7th developmental weeks Ki-67, caspase-3 and TUNEL-positive cells characterized all mesonephric structures, indicating importance of cell proliferation in the growth of the mesonephros and role of apoptosis in nephrogenesis. From the 7th week on, p53 and bcl-2 positive cells appeared in the mesonephros as well. Regressive changes in the mesonephros could be regulated by activation of p53, while bcl-2 could contribute to selective survival of some tubules giving rise to adult structures. In the early human metanephros (5–7 weeks), Ki-67 positive cells characterized all metanephric structures, indicating a role of cell proliferation in branching of the ureteric bud and in nephron formation. During the same period bcl-2, caspase-3 and TUNEL-positive cells were found only in the metanephric mesenchyme and nephrons. Bcl-2 protein probably protected nephrons from apoptosis, while caspase-3 protein controlled cell death in the mesenchyme. At later stages (7–9-weeks), appearance of p53-expressing cells could participate in further morphogenesis of the metanephric collecting system. The factors investigated had a spatially and temporally restricted pattern of appearance in developing kidneys. Changes in that pattern might lead to serious disturbances of kidney formation and function in early childhood.     

Work related diseases and injuries on an oil rig

The analysis of diseases and injuries in the workers on an American oil rig, operating in the Mediterranean Sea, was done in the period of one year, from 1 May 1996 to 1 May 1997. In total, 518 medical examinations of sick and injuried workers were conducted. At the first place in morbidity, there were injuries and poisonings (26.7% of all registered cases). Then followed musculo-skeletal (17.5%), respiratory (14.2%), gastrointestinal diseases (12.1%), mental disorders (10.3%), nervous system (9.2%), skin (6.5%), urogenital (2.9%) and circulatory system diseases (0.6%). Out of all cases, the hand and finger injuries (48.3%) were most frequent, followed by injuries of the leg (13.4%), eye (11.3%), head and neck (10.1%), arm (7.9%), foot (6.7%) and trunk (2.3%). To reduce the incidence of diseases and injuries, special attention should be paid to the workers' basic medical education, to protective measures and providing first aid at the work site.