Psammomys Research Articles

Experimental Exploration of the Soft Tissue Conduction Pathway from Skin Stimulation Site to Inner Ear

Auditory sensation can be elicited by air conduction (AC) and by bone conduction (BC). It is also possible to elicit such responses by applying the standard clinical bone vibrator to the skin over soft tissue sites on the head, neck, or thorax of humans and animals. This mode of auditory stimulation has been called soft tissue conduction (STC). This study was designed to investigate the pathway between soft tissue sites and the ear. The air in the middle ear was replaced with saline solution in an animal with unique anatomy--the fat sand rat, in which about 70% of a thin-walled inner ear bulges into the middle ear bulla cavity--while we recorded the auditory brain stem responses (ABRs) to AC, BC, and STC stimulation. This replacement of air with saline solution led to a significant improvement in STC threshold. With AC stimulation, the ABR threshold was elevated and the latency of the first ABR wave was prolonged. Consistent changes were not seen with BC stimulation. When the air (which has a very low acoustic impedance) that normally surrounds most of the inner ear is replaced with saline solution (which has an acoustic impedance similar to that of soft tissues), the STC threshold is improved. This improvement may be due to improved transmission of acoustic energy from the soft tissues to the inner ear.

Olive Leaf Extract as a Hypoglycemic Agent in Both Human Diabetic Subjects and in Rats

Olive tree (Olea europaea L.) leaves have been widely used in traditional remedies in European and Mediterranean countries as extracts, herbal teas, and powder. They contain several potentially bioactive compounds that may have hypoglycemic properties. To examine the efficacy of 500 mg oral olive leaf extract taken once daily in tablet form versus matching placebo in improving glucose homeostasis in adults with type 2 diabetes (T2DM). In this controlled clinical trial, 79 adults with T2DM were randomized to treatment with 500 mg olive leaf extract tablet taken orally once daily or matching placebo. The study duration was 14 weeks. Measures of glucose homeostasis including Hba1c and plasma insulin were measured and compared by treatment assignment. In a series of animal models, normal, streptozotocin (STZ) diabetic, and sand rats were used in the inverted sac model to determine the mechanism through which olive leaf extract affected starch digestion and absorption. In the randomized clinical trial, the subjects treated with olive leaf extract exhibited significantly lower HbA1c and fasting plasma insulin levels; however, postprandial plasma insulin levels did not differ significantly by treatment group. In the animal models, normal and STZ diabetic rats exhibited significantly reduced starch digestion and absorption after treatment with olive leaf extract compared with intestine without olive leaf treatment. Reduced digestion and absorption was observed in both the mucosal and serosal sides of the intestine. Though reduced, the decline in starch digestion and absorption did not reach statistical significance in the sand rats. Olive leaf extract is associated with improved glucose homeostasis in humans. Animal models indicate that this may be facilitated through the reduction of starch digestion and absorption. Olive leaf extract may represent an effective adjunct therapy that normalizes glucose homeostasis in individuals with diabetes.

Obesity, insulin resistance and diabetes in the sand rat exposed to a hypercaloric diet; possible protective effect for IL1-β

It is well established that, upon changing their natural desert low caloric (succulent halophilic plants) to a regular laboratory high caloric diet, sand rats undergo various phenotypic changes depending on their genetic background and including obesity and various degrees of insulin resistance. Our aim was to investigate the acute effects of Interleukin-1β (IL-1β) and Interferon-γ (IFN-γ) on glucose-induced insulin secretion in normal lean sand rats maintained on their natural diet and in obese insulin resistant normoglycemic or type 2 diabetic animals after a 9-month high caloric diet. Animals were fed either a low or a high caloric diet; after 9 months, pancreatic islets were isolated and incubated in the presence of increasing cytokine concentrations. At the end of the high-energy diet, animals were all over-weight, and probably due to a different genetic background, they displayed either insulin resistance, hyperinsulinemia and normoglycemia or a marked type-2 diabetic state. Pancreatic islets from obese insulin resistant normoglycemic animals were much more sensitive and responsive to IL-1β when compared to lean controls. The cytokine was inefficient in diabetic islets. In conclusion, the markedly increased insulinotropic effect of IL-1β in obese diabetes-resistant sand rat could participate and be involved in pancreatic β-cell hyperactivity that compensates for insulin resistance and thereby prevent the development of type 2 diabetes in these animals.

Effects of morning compared with evening bright light administration to ameliorate short-photoperiod induced depression- and anxiety-like behaviors in a diurnal rodent model

The lack of appropriate animal models for affective disorders is a major factor hindering better understanding of the underlying pathologies and the development of more efficacious treatments. Because circadian rhythms play an important role in affective disorders, we recently suggested that diurnal rodents can be advantageous as model animals. We found that in diurnal rodents, short photoperiod induces depression- and anxiety-like behaviors, with similarities to human seasonal affective disorder. In a pilot study we also found that these behaviors are ameliorated by morning bright light administration. In the present study we further evaluated the effects of morning and evening bright light administration on short photoperiod-induced depression- and anxiety-like behaviors in diurnal fat sand rats. Animals were maintained under short (5L:19D) or neutral (12L:12D) photoperiod and treated with morning or evening bright light or red dim light as control. Morning bright light ameliorated the behavioral deficits in the elevated plus maze and social interaction tests whereas evening bright light was effective only in the social interaction test. This is the first detailed presentation of the effects of bright light treatment in an animal model and a clear demonstration to the advantages of utilizing diurnal rodents to study interactions between circadian rhythms and affect.

Impact of the Glucolipotoxicity In vivo and Insulinotoxicity Inducing in Fibroblast Aortic of Sand Rat (Psammomys obesus)

It was established that the sand rat Psammomys obesus is an experimental model of type diabetes 2 and dyslipidemia, in this in vivo study the sand rats were submitted to natural diet associated with fat (10%) and sucrose (20%) enriched diet /rat per day for 6 months. The initial time and once of the months, plasma parameters were evaluated and at 6th month aortic morphology were examined. To simulate hyperinsulinemic stress, the effects of high dose of insulin 10 UI/ml during 6 h were investigated on subcultured aortic control fibroblasts which were implicated in extracellular matrix remodeling during the atherosclerosis process. In this work report, the proliferation rates, morphological aspects of apoptosis, few markers of oxidative stress (malonaldehyde and nitric oxid) and type I and III collagen contained in extracellular compartment were evaluated. Others animals received a high fat high sucrose diet showed hyperglycemia associated with hyperinsulinemia, dyslipidemia, hyperproteinemia, increase of cardiac markers, low and very low density lipoproteins and decrease high density lipoprotein versus control group. The aortas of diabetic ranimals were exhibited an important disorganization and remodeling of vascular extracellular matrix. In vitro results indicated a decrease in cellular proliferation rate, the apparition of some morphological characters of apoptosis (hypertrophy fibroblasts, hypercondensation chromatin, oncosis) and increase of malonaldehyde, total nitrite production in intracellular compartment and increase of total proteins, type I and III collagen especially type III were observed in extracellular compartment. The high fat high sucrose diet induced diabetes associated with hyperinsulinemia and development of extracellular matrix remodeling in sand rats similar to human advanced atherosclerotic lesions. The high insulin dose induced an increase of both some markers of oxidative stress caused apoptosis and extracellular type III collagen especially.

Islet protection and amelioration of diabetes type 2 in <i>Psammomys obesus</i> by treatment with cannabidiol

Background and purpose: Cannabidiol (CBD), a non-psychoactive component of Cannabis sativa, has been shown by us, to have an anti-inflammatory effect in collagen-induced arthritis in DBA mice and in type 1 diabetes in NOD mice. As inflammation is a process involved in diabetes type 2, we administered CBD to Psammomys obesus (sand rats), a species which develops diabetes type 2 when fed high-energy (HE) diet, to investigate whether we can hinder the development of the disease. Experimental Approach: Male Psammomys obesus were kept on a high energy diet during the experiments. They were treated with CBD (i.p injection, 5 mg/kg, 5 times/week) for 4 weeks and kept (without CBD) for another 29 - 39 days. The weights of the animals as well as blood glucose and plasma insulin levels were determined and the morphology of the pancreatic islets was examined. Key results: CBD significantly reduced blood glucose levels in Psammomys obesus, without effecting body weight. Plasma insulin levels were significantly higher in the CBD-treated group. The most striking effect noted was the marked decrease of the destruction of pancreatic islets and beta cells. Conclusions and implications: CBD partially protects pancreatic islets and beta cells from destruction. CBD lowers significantly the blood glucose level and increases insulin level in Psammomys obesus with diabetes type 2, but does not lead to obesity. As CBD already has been administered to patients for other medical indications we propose its use as a therapeutic agent in diabetes type 2.

Extension de Leishmania major au nord de l’Algérie

Since a long time, Leishmania major and L. infantum foci in Algeria were geographically separated by the mountains of the Tell Atlas which represent a natural barrier. Recently, a new focus of cutaneous leishmaniasis (CL) has emerged in the village of El M'hir, located on the north side of the chain of the Tell Atlas, in the basin of the Soummam. During the period 2004-2010, 152 CL cases have been registered and 12 isolates were obtained from patients who declared never having been outside the village the last years. The identification of the parasites showed that all strains belonged to L major MON-25. Investigations on the reservoir hosts showed the presence of the sand rat (Psammomys obesus), for the first time, in this locality. Five strains isolated from this rodent belonged to L. major MON-25. The sand rat, which is usually observed around the chotts in the Saharan and steppe areas, acts as the main reservoir of L. major in Algeria. Its presence in the new focus of El M'hir is reported for the first time. Entomological surveys carried out in 2009 showed the predominance of two sandfly species: Phlebotomus papatasi and P. perniciosus. The first one is known as a vector of L major in the Algerian Sahara. This study highlights the spread of L. major from the arid zones towards the semi arid areas, particularly in the Soummam valley. Climate changes and desertification observed in the steppe area northern Sahara could play a role in the extension of the disease.

Simplified and improved monitoring traps for sampling sand flies

Simplified and improved monitoring traps for sampling sand flies Gunter C. Muller1, Edita, E. Revay2, and John C. Beier3 1Department of Microbiology and Molecular Genetics , IMRIC, Kuvin Centre for the Study of Infectious and Tropical Diseases, Faculty of Medicine, Hebrew University, Jerusalem 91120, Israel, guntercmuller@hotmail.com 2Department of Anatomy and Cell Biology, Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel 3Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, FL 33136, U.S.A.

The Sand Rat,Psammomys obesus, Develops Type 2 Diabetic Retinopathy Similar to Humans

Diabetic retinopathy (DR) is a leading cause of blindness, yet pertinent animal models are uncommon. The sand rat (Psammomys obesus), exhibiting diet-induced metabolic syndrome, might constitute a relevant model. Adult P. obesus (n = 39) were maintained in captivity for 4 to 7 months and fed either vegetation-based diets (n = 13) or standard rat chow (n = 26). Although plant-fed animals exhibited uniform body weight and blood glucose levels over time, nearly 60% of rat chow-raised animals developed diabetes-like symptoms (test group). Animals were killed, and their eyes and vitreous were processed for immunochemistry. Compared with plant-fed animals, diabetic animals showed many abnormal vascular features, including vasodilation, tortuosity, and pericyte loss within the blood vessels, hyperproteinemia and elevated ratios of proangiogenic and antiangiogenic growth factors in the vitreous, and blood-retinal barrier breakdown. Furthermore, there were statistically significant decreases in retinal cell layer thicknesses and densities, accompanied by profound alterations in glia (downregulation of glutamine synthetase, glutamate-aspartate transporter, upregulation of glial fibrillar acidic protein) and many neurons (reduced expression of protein kinase Cα and Cξ in bipolar cells, axonal degeneration in ganglion cells). Cone photoreceptors were particularly affected, with reduced expression of short- and mid-/long-wavelength opsins. Hypercaloric diet nondiabetic animals showed intermediate values. Simple dietary modulation of P. obesus induces a rapid and severe phenotype closely resembling human type 2 DR. This species presents a valuable novel experimental model for probing the neural (especially cone photoreceptor) pathogenic modifications that are difficult to study in humans and for screening therapeutic strategies.

Anti-diabetic activity of Chiliadenus iphionoides

Ethnopharmacological relevanceChiliadenus iphionoides (Boiss. & Blanche) Brullo (Asteraceae), a small aromatic shrub found throughout Israel, is used traditionally in the treatment of diabetes mellitus. In this study, Chiliadenus iphionoides anti-diabetic activity was characterized using cellular and animal models. Materials and methodsPancreatic β cells, adipocytes, and skeletal myotubes were treated with an ethanolic extract of Chiliadenus iphionoides to study the extract's effects on insulin secretion and glucose uptake. The sand rat (Psammomys obesus) was used to study Chiliadenus iphionoides acute and long term effects in vivo. An oral starch tolerance test was performed as well as a 30 day feeding study. ResultsChiliadenus iphionoides extract increased insulin secretion in β cells as well as glucose uptake in adipocytes and skeletal myotubes. The extract also displayed hypoglycemic activity in the diabetic sand rat. ConclusionsChiliadenus iphionoides exhibits considerable anti-diabetic activity, although the mechanism of action remains to be determined.

Superior Canal Dehiscence Effect on Hearing Thresholds

Superior semicircular dehiscence syndrome is associated with vestibular symptoms and an air-bone gap component in the audiogram, apparently caused by the creation of a pathological bony "third window" in the superior semicircular canal. The aim of this study was to evaluate changes in auditory air- and bone-conduction thresholds to low- and high-frequency stimuli in an animal model of a bony fenestration facing the aerated mastoid cavity. Anatomic, audiological. Tertiary university-affiliated medical center. A small hole was drilled in the bony apical portion of the superior semicircular canal facing the mastoid bulla/cavity, with preservation of the membranous labyrinth, in 5 adult-size fat sand rats. Auditory brain stem responses to clicks and 1-kHz tone bursts delivered by air and bone conduction before surgery, after opening the bulla, and after fenestration. After fenestration, a significant air-bone gap was measured in response to clicks (mean ± standard deviation, 37 ± 5.8 dB) and bursts (mean ± standard deviation, 34 ± 14.5 dB). The gap was attributable solely to the significant deterioration in air-conduction thresholds, in the absence of a significant change in bone conduction thresholds. The pattern of auditory brain response changes closely resembled that reported for middle ear dysfunction, namely, an increase in absolute latency of waves I, III, and V without significant alterations in interpeak latency differences. Bony fenestration of the superior semicircular canal toward an aerated cavity in a rodent model mimics the auditory loss pattern of patients with superior semicircular dehiscence syndrome. The dehiscent membrane accounts for the auditory changes.

Bone conduction activation through soft tissues following complete immobilization of the ossicular chain, stapes footplate and round window

Classically it has been thought that bone conduction activation at the mastoid leads to relative motion between the stapes footplate and the oval window due to inertial and to compression (distortion) mechanisms. However, several recent clinical findings and experimental manipulations may point to additional mechanisms. These manipulations were extended in the present study. In ten fat sand rats, following obliteration of one ear, auditory nerve brainstem evoked response (ABR) thresholds were recorded in response to broad band click stimuli, either air conducted (AC) through insert earphones or bone conducted (BC) delivered directly to the exposed skull bone. Following this, the entire ossicular chain, stapes footplate and round window were completely immobilized with super glue, leading to a mean AC threshold elevation of 44 dB, but to a mean BC threshold change (elevation) of only 3.5 dB. In this state of complete immobilization, the bone vibrator was applied to a pool of saline in the surgical area and ABR was elicited with a mean threshold which was not significantly different from that of the BC threshold. When the bone vibrator was then applied to the eye without touching the bone at the orbit, the resulting ABR threshold was about 20 dB greater than the BC threshold. In conclusion, BC stimulation can activate the cochlea without two mobile windows. Furthermore, the cochlea can be activated by a fluid pathway and by application of a bone vibrator to non-osseous sites (soft tissue conduction).

Genetic variation in SH3-domain GRB2-like (endophilin)-interacting protein 1 has a major impact on fat mass

The SH3-domain GRB2-like (endophilin)-interacting protein 1 (SGIP1) gene has been shown to be differentially expressed in the hypothalamus of lean versus obese Israeli sand rats (Psammomys obesus), and is suspected of having a role in regulating food intake. The purpose of this study was to assess the role of genetic variation in SGIP1 in human disease. We performed single-nucleotide polymorphism (SNP) genotyping in a large family pedigree cohort from the island of Mauritius. The Mauritius Family Study (MFS) consists of 400 individuals from 24 Indo-Mauritian families recruited from the genetically homogeneous population of Mauritius. We measured markers of the metabolic syndrome, including diabetes and obesity-related phenotypes such as fasting plasma glucose, waist:hip ratio, body mass index and fat mass. Statistical genetic analysis revealed associations between SGIP1 polymorphisms and fat mass (in kilograms) as measured by bioimpedance. SNP genotyping identified associations between several genetic variants and fat mass, with the strongest association for rs2146905 (P=4.7 × 10(-5)). A strong allelic effect was noted for several SNPs where fat mass was reduced by up to 9.4% for individuals homozygous for the minor allele. Our results show association between genetic variants in SGIP1 and fat mass. We provide evidence that variation in SGIP1 is a potentially important determinant of obesity-related traits in humans.

Diurnal rodents as animal models of human central vision: characterisation of the retina of the sand rat Psammomys obsesus

Cone photoreceptor-based central vision is of paramount importance in human eyesight, and the increasing numbers of persons affected by macular degeneration emphasizes the need for relevant and amenable animal models. Although laboratory mice and rats have provided valuable information on retinal diseases, they have inherent limitations for studies on macular pathology. In the present study, we extend our recent analyses of diurnal murid rodents to demonstrate that the sand rat Psammomys obesus has a remarkably cone-rich retina, and represents a useful adjunct to available animal models of central vision. Adult P. obesus were captured and transferred to animal facilities where they were maintained under standard light/dark cycles. Animals were euthanised and their eyes enucleated. Tissue was either fixed in paraformaldehyde and prepared for immunohistochemistry, or solubilized in lysis buffer and separated by SDS-PAGE and subjected to western blot analysis. Samples were labelled with a battery of antibodies against rod and cone photoreceptors, inner retinal neurones, and glia. P. obesus showed a high percentage of cones, 41% of total photoreceptor numbers in both central and peripheral retina. They expressed multiple cone-specific proteins, including short and medium-wavelength opsin and cone transducin. A second remarkable feature of the retina concerned the horizontal cells, which expressed high levels of glial fibrillar acidic protein and occludin, two proteins which are not seen in other species. The retina of P. obesus displays high numbers of morphologically and immunologically identifiable cones which will facilitate analysis of cone pathophysiology in this species. The unusual horizontal cell phenotype may be related to the cone distribution or to an alternative facet of the animals lifestyle.

Imidacloprid as a potential agent for the systemic control of sand flies

Our goal was to study the effectiveness of the insecticide imidacloprid as a systemic control agent. First, to evaluate the blood-feeding effect, we fed adult female Phlebotomus papatasi with imidacloprid-treated rabbit blood and monitored blood-feeding success and survival. Second, to evaluate the feed-through effectiveness of this insecticide, we fed laboratory rats and sand rats with insecticide-treated food and evaluated the survival of sand fly larvae feeding on rodents' feces. In the blood-feeding experiment, 89.8% mortality was observed with the higher dose (5 mg/ml) and 81.3% with the lower dose (1 mg/ml). In the larvicide experiments, both sand fly species demonstrated a typical dose-response curve with the strongest lethal effect for the 250 ppm samples. Lutzomyia longipalpis larvae, however, were less sensitive. In all experiments, 1(st) instar larvae were more sensitive than the older stages. First instar P. papatasi larvae feeding on sand rat feces passed the larvicidal threshold of 90% mortality at doses higher than 50 ppm. In comparison, in older stages 90% mortality was obtained with a dose of only 250 ppm. Overall, results support the feasibility of imidacloprid as a systemic control agent that takes advantage of the tight ecological association between the reservoir host and the sand fly vector.

Colchicine prolongs patency of myringotomy in an animal model

ObjectiveChronic otitis media with effusion (COME) is a frequently observed condition in childhood. The most common and effective surgical therapy for COME is myringotomy with insertion of a ventilation tube (VT). Our aims were to investigate the combined effect of myringotomy and the topical application of Colchicine solution to the external ear canal for the prolongation of patency in the treatment of patients with COME and to evaluate the ototoxicity of Colchicine applied directly to the middle ear. MethodsA prospective study on 47 ears in 26 fat sand rats was fashioned. In the first phase, solutions of different concentrations of Colchicine were applied to the middle ear cavity in order to determine the drug's ototoxicity, assessing inner ear function with ABR. In the second phase myringotomy was performed and a non ototoxic concentration of Colchicine applied to 12 external ear canals, while saline was applied to nine. ResultsIn the first phase, Colchicine concentration of 0.1% and higher applied to the middle ear cavity caused an ABR threshold elevation. In the second phase, the mean closure time after 0.01% Colchicine application was prolonged to >2.14 weeks (P<0.05). ConclusionColchicine has a proven potential for prolongation of myringotomy patency when applied as a solution to the external ear as a 0.01% solution. Further investigations are required to validate these results in humans and to study the potential effect of repetitive Colchicine application on the duration of myringotomy patency for the treatment of COME.

Leupeptin reduces impulse noise induced hearing loss

BackgroundExposure to continuous and impulse noise can induce a hearing loss. Leupeptin is an inhibitor of the calpains, a family of calcium-activated proteases which promote cell death. The objective of this study is to assess whether Leupeptin could reduce the hearing loss resulting from rifle impulse noise.MethodsA polyethelene tube was implanted into middle ear cavities of eight fat sand rats (16 ears). Following determination of auditory nerve brainstem evoked response (ABR) threshold in each ear, the animals were exposed to the noise of 10 M16 rifle shots. Immediately after the exposure, saline was then applied to one (control) ear and non-toxic concentrations of leupeptin determined in the first phase of the study were applied to the other ear, for four consecutive days.ResultsEight days after the exposure, the threshold shift (ABR) in the control ears was significantly greater (44 dB) than in the leupeptin ears (27 dB).ConclusionLeupeptin applied to the middle ear cavity can reduce the hearing loss resulting from exposure to impulse noise.

Intermittent fasting modulation of the diabetic syndrome in sand rats. III. Post-mortem investigations

The present report concerns several post-mortem variables examined in sand rats that were either maintained on a vegetal diet (control animals) or exposed first during a 20-day transition period to a mixed diet consisting of a fixed amount of a hypercaloric food and decreasing amounts of the vegetal food and then to a 30-day experimental period of exposure to the hypercaloric food. During the latter period, all animals were either given free access to food or fasting daily for 15 h, i.e. from 5.00 p.m. to 8.00 a.m. The body weight, liver wet weight, pancreas wet weight, plasma glucose and haemoglobin A1c concentration, plasma insulin concentration, insulinogenic index, insulin resistance HOMA, plasma cholesterol and triglyceride concentration, liver triglyceride and phospholipid content were all measured. Pancreatic islet (insulin, GLUT2) and liver (lipid droplets) histology were also examined. The main findings consisted in a lower body weight of fasting than non-fasting animals, a higher liver weight in non-diabetic and diabetic rats than in control non-fasting (but not so in fasting) animals, a decrease of pancreas weight in non-diabetic and diabetic as distinct from control animals, a fasting-induced decrease in plasma glucose, plasma insulin and insulin resistance HOMA, plasma cholesterol and triglyceride concentration and triglyceride liver content.

Leg Amputation Accelerates Senescence of Rat Lumbar Intervertebral Discs

Several senescence biomarkers were observed to investigate cell senescence in degenerative intervertebral lumbar discs of foreleg-amputated rats. To determine if cell senescence is accelerated in degenerative intervertebral lumbar disc cells in an upright-rat model. Cellular senescence was accelerated in human and sand rat degenerative intervertebral disc (IVD) cells. Repeated use of upright posture by rats contributed to degenerative disc changes. No convincing evidence of cell senescence was observed in the lumbar disc of the foreleg amputated rat. The forelimbs of 20 rats were amputated at 1 month of age such that they maintained an upright stance; rats were housed in custom-made cages. Nonamputated rats, also 1 month of age, were kept in regular cages and served as a control group. The lumbar IVDs were harvested from rats in 2 groups, at 5 or 9 months following amputation. Senescence-associated-β-galactosidase-positive staining was used to detect cell senescence. p16INK4a and p27KIP were assessed by immunohistochemistry analysis. Total RNA isolated from these samples was used to measure the gene expression of p16INK4a, RB, cyclin D1, CDK4, PTEN, p27KIP, p19ARF, p21, TERT, and RAGE by real-time polymerase chain reaction assay. The highest levels of SA-β-GAL activity were detected in 9-month amputated rats. Quantitative immunohistochemical analysis showed that there were highest rates of p16INK4a and p27KIP protein expression in the cartilage endplate and anulus fibrosus of 9-month amputated rats. The mRNA levels of p16INK4a, RB, PTEN, p27KIP, p19ARF, and RAGE were upregulated. The increased cyclin D1 mRNA level was statistically significant only at the ninth month following amputation; CDK4 and TERT mRNA levels were downregulated to a similar extent at both points compared with nonamputated controls. mRNA expression of p21 was significantly downregulated. Accelerated cell senescence was associated with forelimb amputation that causes abnormal loading in rat lumbar IVDs.

New Rural Focus of Plague, Algeria

New Rural Focus of Plague, Algeria