Levels Of Degeneration Research Articles

Effects of wheat and corn gluten on growth performance, histopathologic and autoimmune metabolism of entero-hepatictissue in lambs

This study investigated the effects of wheat gluten and corn gluten, alone as a protein source into rations as protein sources, on fattening performance and the histopathological and autoimmune metabolism of the small intestinal and hepatic tissues in lambs. The animals enrolled in the study were fed on isonitrogenous and isoenergetic diets. The protein sources provided to the animals were soybean meal and safflower meal in the control group, wheat gluten in Group Wheat, and corn gluten in Group Corn. The study animals included 24 male Morkaraman (Red Karaman) lambs, which were of a mean age of 9 months and assigned to three groups, each of 8 animals. Mean daily body weight gain (0-56 day) were observed to be significantly lower in Group Wheat (p<0.05). Mean daily feed intake were observed to be significantly lower in Group Wheat and Group Corn (p<0.05). At the end of the study, when compared to the control group, Group Wheat displayed significantly higher levels of villous atrophy, inflammation, crypt hyperplasia and transglutaminase immunopositivity in the small intestinal tissue as well as necrosis, inflammation, bile duct hyperplasia and transglutaminase immunopositivity in the hepatic tissue, and a lower level of degeneration in the liver (p<0.05). The findings detected in Group Corn were variable. In result, wheat gluten significantly affected both performance parameters and the histopathological and autoimmune metabolism of the intestinal and hepatic tissues in lambs. Key words: Corn; gluten; lamb; wheat; histopathological

Evaluation of damage discrimination in dopaminergic neurons using dopamine transporter PET tracer [18F]FECNT-d4

BackgroundParkinson’s disease (PD) is a prevalent neurodegenerative disorder worldwide, diagnosed based on classic symptoms like motor dysfunction and cognitive impairments. With the development of various radioactive ligands, positron emission tomography (PET) imaging combined with specific radiolabelling probes has proven to be effective in aiding clinical PD diagnosis. Among these probes, 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl) nortropane ([18F]FECNT) has been utilized as a PET tracer to image dopamine transporter (DAT) integrity in striatal presynaptic dopaminergic terminals. However, the presence of brain-penetrant radioactive metabolites produced by [18F]FECNT may impact the accuracy of PET imaging. In previous research, we developed 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl-1,1,2,2-d4) nortropane ([18F]FECNT-d4), a deuterated derivative with enhanced stability in plasma and the striatum, along with a slower washout rate. In this study, we further investigated the potential of [18F]FECNT-d4 to detect dopaminergic neuron degeneration in Parkinson’s disease. This involved PET imaging in unilaterally-lesioned PD model rats and in vitro autoradiography conducted on postmortem brain sections.ResultsPET images revealed reduced specific uptake in the ipsilateral striatum of rats stereotactically injected with 6-hydroxydopamine hydrochloride (6-OHDA). Compared to the sham group, the ratio of standardized uptake value (SUV) in the ipsilateral to contralateral striatum decreased by 13%, 23%, and 63% in the mild, moderate, and severe lesioned groups, respectively. Dopaminergic denervation observed in PET imaging was further supported by behavioral assessments, immunostaining, and monoamine concentration tests. Moreover, the microPET results exhibited positive correlations with these measurements, except for the apomorphine-induced rotational behavior test, which showed a negative correlation. Additionally, [18F]FECNT-d4 uptake was approximately 40% lower in the postmortem striatal sections of a PD patient compared to a healthy subject. Furthermore, estimated human dosimetry (effective dose equivalent: 5.06 E-03 mSv/MBq), extrapolated from rat biodistribution data, remained below the current Food and Drug Administration limit for radiation exposure.ConclusionOur findings demonstrate that [18F]FECNT-d4 accurately estimates levels of dopaminergic neuron degeneration in the 6-OHDA-induced PD rat model and effectively distinguishes between PD patients and healthy individuals. This highly sensitive and safe PET probe holds promising potential for clinical application in the diagnosis and monitoring of Parkinson’s disease.

Significance of Fibrillin-1, Filamin A, MMP2 and SOX9 in Mitral Valve Pathology.

Genetic factors play a significant role in the pathogenesis of mitral valve diseases, including mitral valve prolapse (MVP) and mitral valve regurgitation. Genes like Fibrillin-1 (FBN1), Filamin A (FLNA), matrix metalloproteinase 2 (MMP2), and SRY-box transcription factor 9 (SOX9) are known to influence mitral valve pathology but knowledge of the exact mechanism is far from clear. Data regarding serum parameters, transesophageal echocardiography, and genetic and histopathologic parameters were investigated in 54 patients who underwent cardiovascular surgery for mitral valve regurgitation. The possible association between Fibrillin-1, Filamin A, MMP2, and SOX9 gene expressions was checked in relationship with the parameters of systemic inflammatory response. The mRNA expression levels (RQ-relative quantification) were categorized into three distinct groups: low (RQ < 1), medium/normal (RQ = 1-2), and high (RQ > 2). Severe fibrosis of the mitral valve was reflected by high expression of FBN1 and low expression of MMP2 (p < 0.05). The myxoid degeneration level was associated with the mRNA expression level for FBN1 and a low lymphocyte-monocyte ratio was associated with an increased mRNA expression of FBN1 (p < 0.05). A high number of monocytes was associated with high values of FBN1 whereas the increase in the number of lymphocytes was associated with high levels of MMP2. In addition, we observed that the risk of severe hyalinization was enhanced by a low mRNA expression of FLNA and/or SOX9. In conclusion, a lower FLNA mRNA expression can reflect the aging process that is highlighted in mitral valve pathology as a higher risk for hyalinization, especially in males, that might be prevented by upregulation of the SOX9 gene. FBN1 and MMP2 influence the inflammation-related fibrotic degeneration of the mitral valve. Understanding the genetic base of mitral valve pathology can provide insights into disease mechanisms, risk stratification, and potential therapeutic targets.

The Relationship Between Craniocervical Morphology and the Presence and Level of Cervical Facet Joint Degeneration.

To investigate the relationship between craniocervical morphology and the presence and level of cervical facet joint degeneration (FJD). A total of 108 consecutive female patients aged 45-55 years who had undergone neck + brain CT angiography were included in this retrospective sectional study. Only patients of a certain age and of the same gender were included in order to eliminate the differences that create a disposition to the development of spinal degeneration. The presence of facet joint (FJ) arthritis (grade ≥2 degeneration in at least one affected facet joint) and the grade of the facet joint degeneration for each patient were recorded. A total of 20 lengths and 3 angles of craniocervical morphology were measured. The differences between the individuals with and without FJ arthritis were investigated with the independent-sample t test, and the relationship between the FJD grade and craniocervical morphology was investigated using the Spearman correlation test. Individuals with FJ arthritis were found to have longer Grabb-Oakes measurement, shorter FM AP length, lower ADI, lower EOP thickness, higher clivus length, higher crista gall-ATS distance, lower CCA angle, lower distance between the C1 vertebra lateral masses, and higher BAI than those without FJ arthritis (P ˂ 0.05). Besides, we found that the FJD grade increased as the Grabb-Oakes measurement increased, ADI distance decreased, FM AP length decreased, EOP thickness decreased, clivus length increased, basal angle increased, distance between the C1 vertebra lateral masses decreased, and BAI increased (P ˂ 0.05). Differences in craniocervical morphology are statistically associated with degenerative processes that result in degenerative changes in the facet joint. Therefore, some morphological changes in craniocervical anatomy cause changes in the momentum and distribution of the load on the facet joints, predisposing the patient to facet arthropathy and osteoarthritis.

Astrocyte reactivity is associated with tau tangle load and cortical thinning in Alzheimer’s disease

BackgroundIt is not fully established whether plasma β-amyloid(Aβ)42/Aβ40 and phosphorylated Tau181 (p-Tau181) can effectively detect Alzheimer’s disease (AD) pathophysiology in older Chinese adults and how these biomarkers correlate with astrocyte reactivity, Aβ plaque deposition, tau tangle aggregation, and neurodegeneration.MethodsWe recruited 470 older adults and analyzed plasma Aβ42/Aβ40, p-Tau181, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) using the Simoa platform. Among them, 301, 195, and 70 underwent magnetic resonance imaging, Aβ and tau positron emission tomography imaging. The plasma Aβ42/Aβ40 and p-Tau181 thresholds were defined as ≤0.0609 and ≥2.418 based on the receiver operating characteristic curve analysis using the Youden index by comparing Aβ-PET negative cognitively unimpaired individuals and Aβ-PET positive cognitively impaired patients. To evaluate the feasibility of using plasma Aβ42/Aβ40 (A) and p-Tau181 (T) to detect AD and understand how astrocyte reactivity affects this process, we compared plasma GFAP, Aβ plaque, tau tangle, plasma NfL, hippocampal volume, and temporal-metaROI cortical thickness between different plasma A/T profiles and explored their relations with each other using general linear models, including age, sex, APOE-ε4, and diagnosis as covariates.ResultsPlasma A+/T + individuals showed the highest levels of astrocyte reactivity, Aβ plaque, tau tangle, and axonal degeneration, and the lowest hippocampal volume and temporal-metaROI cortical thickness. Lower plasma Aβ42/Aβ40 and higher plasma p-Tau181 were independently and synergistically correlated with higher plasma GFAP and Aβ plaque. Elevated plasma p-Tau181 and GFAP concentrations were directly and interactively associated with more tau tangle formation. Regarding neurodegeneration, higher plasma p-Tau181 and GFAP concentrations strongly correlated with more axonal degeneration, as measured by plasma NfL, and lower plasma Aβ42/Aβ40 and higher plasma p-Tau181 were related to greater hippocampal atrophy. Higher plasma GFAP levels were associated with thinner cortical thickness and significantly interacted with lower plasma Aβ42/Aβ40 and higher plasma p-Tau181 in predicting more temporal-metaROI cortical thinning. Voxel-wise imaging analysis confirmed these findings.DiscussionThis study provides a valuable reference for using plasma biomarkers to detect AD in the Chinese community population and offers novel insights into how astrocyte reactivity contributes to AD progression, highlighting the importance of targeting reactive astrogliosis to prevent AD.

Should the pelvis be included? An analysis of distal junctional failure risk factors in correcting adult spinal deformity in women with fusion to L5.

To identify the risk factors for distal junctional failure (DJF) in women treated for adult spine deformity with fusion to L5 and to highlight the significance of preoperative assessment, surgical decision-making, and postoperative care. This is a retrospective study of data collected prospectively on the local institutional spine surgery registry (2016-2021). All patients, women older than 18 years, with a diagnosis of adult spine deformity who underwent long posterior instrumentation to L5 and had a minimum of 2-years follow-up were included in the study (two groups: with or without DJF). Demographic and radiographic data, corrective strategy, preoperative level of degeneration at L5/S1 and GAP score were compared between the two groups. Forty-eight patients (n = 48) satisfied eligibility criteria. At two-years follow-up, nine patients (18,7%) developed a DJF that required surgical revision. Thirty-nine patients did not present distal junctional complications. Patients with or without DJF showed significant differences in terms of preoperative spinopelvic parameters (PT: 28°± 6° vs. 23°± 9°, p-value 0.05; DJF group vs. not DJF) and degeneration of L5-S1 (Pfirmann grade L5-S1 disc 3.7 ± 1.0 vs. 2.6 ± 0.8, p-value 0.001; DJF group vs. not DJF) (L5-S1 Facet joint Osteoarthritis 3.1 ± 0.8 vs.2.4 ± 0.8, p-value 0.023; DJF group vs. not DJF). DJF following spinal deformity correction surgery is influenced by a combination of patient-related, surgical and implant-related factors. Fusion construct length, preoperative and postoperative sagittal alignment and the grade of degeneration of the distal disc have been identified as significant risk factors. Surgeons should carefully evaluate these factors and employ appropriate strategies.

Carbon monoxide-releasing molecule-3 exerts neuroprotection effects after cardiac arrest in mice: A randomized controlled study

BackgroundPost-cardiac arrest brain injury (PCABI) is the leading cause of death in survivors of cardiac arrest (CA). Carbon monoxide-releasing molecule (CORM-3) is a water-soluble exogenous carbon monoxide that has been shown to have neuroprotection benefits in several neurological disease models. However, the effects of CORM-3 on PCABI is still unclear. MethodsA mice model combined asystole with hemorrhage was used. Mice were anesthetized and randomized into 4 groups (n = 12/group) and underwent either 9.5 min CA followed by cardiopulmonary resuscitation (CPR) or sham surgery. CORM-3 (30 mg/kg) or vehicle (normal saline) were administered at 1 h after return of spontaneous circulation or sham surgery. Survival, neurologic deficits, alterations in the permeability of the brain-blood barrier and cerebral blood flow, changes of oxidative stress level, level of neuroinflammation and neuronal degeneration, and the activation of Nrf2/HO-1 signaling pathway were measured. ResultsIn CORM-3 treated mice that underwent CA/CPR, significantly improved survival (75.00% vs. 58.33%, P = 0.0146 (24 h) and 66.67% vs. 16.67%, P < 0.0001 (72 h)) and neurological function were observed at 24 h and 72 h after ROSC (P < 0.05 for each). Additionally, increased cerebral blood flow, expression of tight junctions, and reduced reactive oxygen species generation at 24 h after ROSC were observed (P < 0.05 for each). CORM-3 treated mice had less neuron death and alleviated neuroinflammation at 72 h after ROSC (P < 0.05 for each). Notably, the Nrf2/HO-1 signaling pathway was significantly activated in mice subjected to CA/CPR with CORM-3 treatment. ConclusionsCORM-3 could improve survival and exert neuroprotection after CA/CPR in mice. CORM-3 may be a novel and promising pharmacological therapy for PCABI.

Discovery of circulating blood biomarkers in patients with and without Modic changes of the lumbar spine: a preliminary analysis.

The following study aimed to determine the existence of blood biomarkers in symptomatic patients with or without lumbar Modic changes (MC). A cross-sectional sub-analyses of a prospective cohort was performed. Fasting blood samples were collected from patients with and without lumbar MC who had undergone spinal fusion or microdiscectomy. An 80-plex panel and CCL5/RANTES were used to assess preoperative plasma cytokine concentrations. Patient demographics and imaging phenotypes were also assessed. Thirty-one subjects were analysed (n = 18 no MC; n = 13 MC). No significant differences were found in age, sex, body mass index, smoking and alcohol history, and surgical procedure (i.e. fusion, decompression) between the two groups (p > 0.05). Several statistically significant blood biomarkers in MC patients were identified, including elevated levels of C-C Motif Chemokine Ligand 5 (CCL5, p = 0.0006), while Macrophage Migration Inhibitory Factor (MIF) was significantly lower (p = 0.009). Additionally, C-X-C Motif Chemokine Ligand 5 (CXCL5, p = 0.052), Pentraxin 3 (PTX3, p = 0.06) and Galectin-3 (Gal-3, p = 0.07) showed potential relevance. Moreover, MC patients exhibited significantly higher levels of disc degeneration (p = 0.0001) and displacement severity (p = 0.020). Based on multivariate analyses and controlling for disc degeneration/displacement, CCL5 (OR 1.02; 95% CI 1.002-1.033; p = 0.028) and MIF (OR 0.60; 95% CI 0.382-0.951; p = 0.030) were independently associated with MC patients. This "proof-of-concept" study is the first to identify specific and significantly circulating blood biomarkers associated with symptomatic patients with lumbar MC, independent of disc alterations of degeneration and/or bulges/herniations. Specifically, differences in CCL5 and MIF protein levels were significantly noted in MC patients compared to those without MC.

Potential of Dual-Energy CT-Based Collagen Maps for the Assessment of Disk Degeneration in the Lumbar Spine

Rationale and ObjectivesLumbar disk degeneration is a common condition contributing significantly to back pain. The objective of the study was to evaluate the potential of dual-energy CT (DECT)-derived collagen maps for the assessment of lumbar disk degeneration. Patients and MethodsWe conducted a retrospective analysis of 127 patients who underwent dual-source DECT and MRI of the lumbar spine between 07/2019 and 10/2022. The level of lumbar disk degeneration was categorized by three radiologists as follows: no/mild (Pfirrmann 1&2), moderate (Pfirrmann 3&4), and severe (Pfirrmann 5). Recall (sensitivity) and accuracy of DECT collagen maps were calculated. Intraclass correlation coefficient (ICC) was used to evaluate inter-reader reliability. Subjective evaluations were performed using 5-point Likert scales for diagnostic confidence and image quality. ResultsWe evaluated a total of 762 intervertebral disks from 127 patients (median age, 69.7 (range, 23.0 – 93.7), female, 56). MRI identified 230 non/mildly degenerated disks (30.2%), 484 moderately degenerated disks (63.5%), and 48 severely degenerated disks (6.3%). DECT collagen maps yielded an overall accuracy of 85.5% (1955/2286). Recall (sensitivity) was 79.3% (547/690) for the detection of no/mild lumbar disk degeneration, 88.7% (1288/1452) for the detection of moderate disk degeneration, and 83.3% (120/144) for the detection of severe disk degeneration (ICC=0.9). Subjective evaluations of DECT collagen maps showed high diagnostic confidence (median 4) and good image quality (median 4). ConclusionThe use of DECT collagen maps to distinguish different stages of lumbar disk degeneration may have clinical significance in the early diagnosis of disk-related pathologies in patients with contraindications for MRI or in cases of unavailability of MRI.

Phenotypical characterization of exteroceptive sensation and pain symptoms on diabetic patients.

Diabetic neuropathy (DN) is one of the most common complications of diabetes, affecting about half of individuals with the disease. Among the various symptoms of DN, the development of chronic pain stands out and manifests as exacerbated responses to sensorial stimuli. The conventional clinical treatments used for general neuropathy and associated painful symptoms, still brings uncomplete and unsatisfactory pain relief. Patients with neuropathic pain syndromes are heterogeneous. They present with a variety of sensory symptoms and pain qualities which difficult the correct diagnosis of sensory comorbidities and consequently, the appropriate chronic pain management. Herein, we aimed to demonstrate the existence of different sensory profiles on diabetic patients by investigating epidemiological and clinical data on the symptomatology of a group of patients with DN. This is a longitudinal and observational study, with a sample of 57 volunteers diagnosed with diabetes from outpatient day clinic of Hospital Universitário of the University of São Paulo-Brazil. After being invited and signed the Informed Consent Form (ICF), patients were submitted to clinical evaluation and filled out pain and quality of life questionnaires. They also performed quantitative sensory test (QST) and underwent skin biopsy for correlation with cutaneous neuropathology. Data demonstrate that 70% of the studied sample presented some type of pain, manifesting in a neuropathic or nociceptive way, what has a negative impact on the life of patients with DM. We also demonstrated a positive association between pain and anxiety and depression, in addition to pain catastrophic thoughts. Three distinct profiles were identified in the sample, separated according to the symptoms of pain: (i) subjects without pain; (ii) with mild or moderate pain; (iii) subjects with severe pain. We also identified through skin biopsy that diabetic patients presented advanced sensory impairment, as a consequence of the degeneration of the myelinated and unmyelinated peripheral fibers. This study characterized the painful symptoms and exteroceptive sensation profile in these diabetic patients, associated to a considerable level of sensory degeneration, indicating, and reinforcing the importance of the long-term clinical monitoring of individuals diagnosed with DM, regarding their symptom profiles and exteroceptive sensitivity.

A Simple Immunofluorescence Method to Characterize Neurodegeneration and Tyrosine Hydroxylase Reduction in Whole Brain of a Drosophila Model of Parkinson's Disease.

Dopaminergic (DAergic) neurodegeneration in the substantia nigra pars compacta of the human brain is the pathological feature associated with Parkinson's disease (PD). Drosophila also exhibits mobility defects and diminished levels of brain dopamine on exposure to neurotoxicants mimicking PD. Our laboratory demonstrated in a Drosophila model of sporadic PD that there is no decrease in DAergic neuronal number; instead, there is a significant reduction in tyrosine hydroxylase (TH) fluorescence intensity (FI). Here, we present a sensitive assay based on the quantification of FI of the secondary antibody (ab). As the FI is directly proportional to the amount of TH synthesis, its reduction under PD conditions denotes the decrease in the TH synthesis, suggesting DAergic neuronal dysfunction. Therefore, FI quantification is a refined and sensitive method to understand the early stages of DAergic neurodegeneration. FI quantification is performed using the ZEN 2012 SP2 single-user software; a license must be acquired to utilize the imaging system to interactively control image acquisition, image processing, and analysis. This method will be of good use to biologists, as it can also be used with little modification to characterize the extent of degeneration and changes in the level of degeneration in response to drugs in different cell types. Unlike the expensive and cumbersome confocal microscopy, the present method will be an affordable option for fund-constrained neurobiology laboratories. Key features • Allows characterizing the incipient DAergic and other catecholaminergic neurodegeneration, even in the absence of loss of neuronal cell body. • Great alternative for the fund-constrained neurobiology laboratories in developing countries to utilize this method in different cell types and their response to drugs/nutraceuticals.

Fraction of C. d. collilineatus venom containing crotapotin protects PC12 cells against MPP + toxicity by activating the NGF-signaling pathway.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. There is no effective treatment for neurodegenerative diseases. Snake venoms are a cocktail of proteins and peptides with great therapeutic potential and might be useful in the treatment of neurodegenerative diseases. Crotapotin is the acid chain of crotoxin, the major component of Crotalus durissus collilineatus venom. PD is characterized by low levels of neurotrophins, and synaptic and axonal degeneration; therefore, neurotrophic compounds might delay the progression of PD. The neurotrophic potential of crotapotin has not been studied yet. We evaluated the neurotrophic potential of crotapotin in untreated PC12 cells, by assessing the induction of neurite outgrowth. The activation of the NGF signaling pathway was investigated through pharmacological inhibition of its main modulators. Additionally, its neuroprotective and neurorestorative effects were evaluated by assessing neurite outgrowth and cell viability in PC12 cells treated with the dopaminergic neurotoxin MPP+ (1-methyl-4-phenylpyridinium), known to induce Parkinsonism in humans and animal models. Crotapotin induced neuritogenesis in PC12 cells through the NGF-signaling pathway, more specifically, by activating the NGF-selective receptor trkA, and the PI3K/Akt and the MAPK/ERK cascades, which are involved in neuronal survival and differentiation. In addition, crotapotin had no cytotoxic effect and protected PC12 cells against the inhibitory effects of MPP+ on cell viability and differentiation. These findings show, for the first time, that crotapotin has neurotrophic/neuroprotective/neurorestorative potential and might be beneficial in Parkinson's disease. Additional studies are necessary to evaluate the toxicity of crotapotin in other cell models.

Ampiang-Dadih-a combination of Indonesian traditional fermented buffalo milk and black glutinous rice-prevents hypercholesterolemia and liver cell degeneration in vivo: A pilot study.

We aimed to evaluate the potential of Ampiang-Dadih (AD), a combination of Indonesian traditional fermented buffalo milk (Dadih) and black glutinous rice flakes (Ampiang) as an anti-hypercholesterolemic agent and to prevent liver-cell degeneration using a rat model. A mixture of black glutinous rice powder (0.3 gm/gm feed) and fermented buffalo milk (3.74/200 gm BW) was prepared to obtain AD. Fifteen adult male Sprague Dawley rats were divided into three groups of five animals each: (A) negative control group (distilled water; 5 weeks), (B) hypercholesterolemia group (1% cholesterol per feed; 5 weeks), and (C) preventive AD group (1% cholesterol and AD; 5 weeks). The blood lipid profiles were measured at weeks 2, 4, and 5. The liver enzyme activity, cholesterol level, and histology were observed at the end of week 5. AD administration simultaneously with cholesterol in Group C significantly prevented an increase in total plasma cholesterol and low-density lipoprotein levels compared to Group B. Alanine transaminase and aspartate transaminase were maintained at normal levels in Group C. Furthermore, the levels of liver cholesterol and liver cell degeneration in Group C were also maintained because of AD administration compared to that in Group B. This study demonstrated that AD has the potential to be developed as a functional food for hypercholesterolemia prevention.

The Impact of the Placement of the L5 Vertebra in Relation to the Intercrest Line on the Level of Disc Herniation.

To determine whether there is a correlation between a deeply seated L5 vertebra in relation to the intercrest line (ICL) and the level of degeneration of lumbar discs. The study included 152 patients who underwent surgery for lumbar disc herniation. After analyzing the radiographs, the patients were separated into two groups. Group 1 patients had an ICL that passed through the L4 corpus, and Group 2 patients had an ICL that passed through the L4-5 disc distance or the L5 vertebra. Group 1 patients were classified as having a deeply seated L5 vertebra, while Group 2 patients were classified as not having a deeply seated L5 vertebra. The study found that male patients had a significantly higher incidence of a deeply seated L5 vertebra compared to female patients (p=0.003). Patients who underwent surgery at the L4?5 level exhibited disc heights that were notably higher than those who underwent surgery at the L5-S1 level. In Group 1, 68% of the patients had surgery at the L4-5 level, compared to only 41.7% in Group 2 (p=0.009). When investigating the effects of the position of the L5 vertebra in relation to the ICL at the L4-5 and L5-S1 disc levels, the study found that having a deeply seated L5 vertebra protected against L5-S1 disc herniation and that L4-5 disc herniation was more common in these patients. This is believed to be due to the L5?S1 segment being less mobile when the L5 vertebra is deeply seated.

Combining adhesive and nonadhesive injectable hydrogels for intervertebral disc repair in an ovine discectomy model.

Intervertebral disc (IVD) disorders (e.g., herniation) directly contribute to back pain, which is a leading cause of global disability. Next-generation treatments for IVD herniation need advanced preclinical testing to evaluate their ability to repair large defects, prevent reherniation, and limit progressive degeneration. This study tested whether experimental, injectable, and nonbioactive biomaterials could slow IVD degeneration in an ovine discectomy model. Ten skeletally mature sheep (4-5.5 years) experienced partial discectomy injury with cruciate-style annulus fibrosus (AF) defects and 0.1 g nucleus pulposus (NP) removal in the L1-L2, L2-L3, and L3-L4 lumbar IVDs. L4-L5 IVDs were Intact controls. IVD injury levels received: (1) no treatment (Injury), (2) poly (ethylene glycol) diacrylate (PEGDA), (3) genipin-crosslinked fibrin (FibGen), (4) carboxymethylcellulose-methylcellulose (C-MC), or (5) C-MC and FibGen (FibGen + C-MC). Animals healed for 12 weeks, then IVDs were assessed using computed tomography (CT), magnetic resonance (MR) imaging, and histopathology. All repaired IVDs retained ~90% of their preoperative disc height and showed minor degenerative changes by Pfirrmann grading. All repairs had similar disc height loss and Pfirrmann grade as Injury IVDs. Adhesive AF sealants (i.e., PEGDA and FibGen) did not herniate, although repair caused local endplate (EP) changes and inflammation. NP repair biomaterials (i.e., C-MC) and combination repair (i.e., FibGen + C-MC) exhibited lower levels of degeneration, less EP damage, and less severe inflammation; however, C-MC showed signs of herniation via biomaterial expulsion. All repair IVDs were noninferior to Injury IVDs by IVD height loss and Pfirrmann grade. C-MC and FibGen + C-MC IVDs had the best outcomes, and may be appropriate for enhancement with bioactive factors (e.g., cells, growth factors, and miRNAs). Such bioactive factors appear to be necessary to prevent injury-induced IVD degeneration. Application of AF sealants alone (i.e., PEGDA and FibGen) resulted in EP damage and inflammation, particularly for PEGDA IVDs, suggesting further material refinements are needed.

The effects of intratesticular injection of sodium chloride on liveweights, reproductive characteristics, and histological appearance of testes in goat kids

The aim of this study was to investigate the effectiveness of intratesticular injection (ITI) of sodium chloride (NaCl) at two different concentrations for supressing reproductive development in goat kids at two months of age. The experiment was carried out at the experimental unit of Aydın Adnan Menderes University, Çine Vocational School, located in Çine, Aydın, Turkey. The experimental groups were control (C, n = 9), a single ITI of 20% NaCl (T1, n = 8) or 40% NaCl (T2, n = 8). The growth, reproductive characteristics, and histological appearance of the testis in the kids were examined up to nine months of age in different periods. The live weights, scrotal circumference, semen and sexual behavior characteristics were not different among groups. The histogical findings were observed in both testes at nine months of age. Greater intensity of destruction was observed in the testes of T1 and T2 kids than that of C kids. High levels of tubular degeneration were detected in testicular tissue samples in T1 and T2 groups. Based on the results, however, it was concluded that neither 20 nor 40% concentrations of NaCl did ensure the castration effect in the goat kids.

Comparison between enzymatic and molecular diagnostic techniques for identification of Meloidogyne spp. on coffee in Brazil and restricted occurrence of M. izalcoensis

Root-knot nematodes (RKNs), Meloidogyne spp. are considered important pathogens of the coffee crop, limiting production and causing economic losses. Meloidogyne izalcoensis was recently detected in the Triângulo Mineiro region, Minas Gerais (MG) state of Brazil, parasitizing coffee plants. To investigate the distribution of this particular nematode species in this region, two small prospective surveys targeting Meloidogyne spp. on coffee plantations were carried out, employing two different techniques (esterase phenotypes (Est) and SCAR markers) in the municipalities of Araguari and Indianópolis where M. izalcoensis had been previously detected. Unfortunately, the high level of female degeneration in the second survey prevented us from identifying the species using esterase phenotypes. In both surveys, we employed the SCAR-coffee Kit, which proved to be highly effective in accurately identifying all the species of Meloidogyne found in coffee plants especially M. exigua. By using eggs and second stage juveniles (J2s) extracted from coffee roots, we obtained reliable markers for the identification of M. exigua (41.67%), M. incognita (33.33%), M. paranaensis (20.83%) and M. izalcoensis (4.17%), which can be used as unique tools in multiplex in the characterization of Meloidogyne spp. from coffee. Mixed population species were also observed in 20.83% of the samples. The use of SCAR markers proved to be the most effective tool for accurately identifying M. exigua and mixed species. These surveys confirmed that M. izalcoensis has a restricted occurrence in the region where it was initially detected.

Correlation of MRI Findings with ODI and VAS Score in Patients with Lower Back Pain

Background: In clinical practice, there is a very common discrepancy between the clinical findings of patients with lumboischialgia and the radiological findings. Objective: This research aimed to determine the degree of correlation between the ODI index and the VAS scale with degenerative changes in the lumbar spine found using MRI. Methods: The study included 100 patients, who were referred for an MRI of the lumbar spine and who had a clear clinical picture of lumboischialgia. Patients underwent MRI. Degenerative changes in the lumbar spine and discs were analysed. Patients were asked to answer the questions in the questionnaire about the subjective feeling of pain and functional status, and ODI and VAS scores were calculated. Results: There has been a statistically significant correlation found between the answers to the survey questions and the VAS score (p &lt; 0.001). There was a significant correlation obtained between the level of degeneration and the disability index (p = 0.022), while the correlation with the VAS score has not been found to be significant (p = 0.325). Conclusion: This study has demonstrated a significant correlation between the VAS pain score and the ODI, as well as a significant correlation between the level of degeneration on MRI scans and the disability index; however, the correlation of MRI scan results with VAS score has not been found to be significant.

Inhibition of PP2A ameliorates intervertebral disc degeneration by reducing annulus fibrosus cells apoptosis via p38/MAPK signal pathway

BackgroundIntervertebral disc degeneration (IVDD) is considered one of the main reasons for low back pain (LBP). To date, the specific pathology of IVDD remains unclear. The annulus fibrosus (AF) is an important part of the intervertebral disc, and AF cell oxidative stress, apoptosis plays a vital role in disc degeneration. Protein phosphatase 2 A (PP2A), a serine/threonine phosphatase, has regulatory functions in various processes, including apoptosis and autophagy. However, thus far, the effect of PP2A on IVDD is not clear. MethodsAF cells derived from caudal intervertebral discs in SD rats were used to analyze the levels of oxidative stress, apoptosis and degeneration as well as PP2A expression. A PP2A agonist (FTY720), inhibitor (microcystin-LR) and siRNA (si-PPP2CA) were employed in IVDD induced by H2O2 to investigate the levels of apoptosis and degeneration. The p38/MAPK signal pathways were evaluated, and a p38 inhibitor (SB203580) and ERK inhibitor (U0126) were added for verification. Finally, FTY720 and microcystin-LR were administered to IVDD rats to assess the effects on levels of apoptosis and degeneration and the relief of IVDD. ResultsThe expression of PP2A was increased in rat AF cells after H2O2 intervention.The levels of apoptosis and degeneration were higher with upregulation of PP2A but were significantly reduced after inhibition of PP2A. The PP2A inhibitor relieved cell apoptosis and degeneration by downregulating the p38/MAPK pathway. In vivo, the knockdown of PP2A resulted in a more complete morphology of discs and less apoptotic and degenerative expression. ConclusionsThis study suggests that the downregulation of PP2 A could reduce AF cell apoptosis and degeneration via the p38/MAPK pathway. It also revealed that the inhibition of PP2 A is expected to be a therapeutic target for IVDD.

Chemonucleolysis combined with dynamic loading for inducing degeneration in bovine caudal intervertebral discs.

Chemonucleolysis has become an established method of producing whole organ culture models of intervertebral disc (IVD) degeneration. However, the field needs more side-by-side comparisons of the degenerative effects of the major enzymes used in chemonucleolysis towards gaining a greater understanding of how these organ culture models mimic the wide spectrum of characteristics observed in human degeneration. In the current work we induced chemonucleolysis in bovine coccygeal IVDs with 100µL of papain (65U/mL), chondroitinase ABC (chABC, 5U/mL), or collagenase II (col'ase, 0.5U/mL). Each enzyme was applied in a concentration projected to produce moderate levels of degeneration. After 7days of culture with daily dynamic physiological loading (0.02-0.2MPa, 0.2Hz, 2h), the cellular, biochemical and histological properties of the IVDs were evaluated in comparison to a PBS-injected control. Papain and collagenase, but not chABC, produced macroscopic voids in the tissues. Compared to day 0 intact IVDs, papain induced the greatest magnitude glycosaminoglycan (GAG) loss compared to chABC and col'ase. Papain also induced the greatest height loss (3%), compared to 0.7%, 1.2% and 0.4% for chABC, col'ase, and PBS, respectively. Cell viability in the region adjacent to papain and PBS-injection remained at nearly 100% over the 7-day culture period, whereas it was reduced to 60%-70% by chABC and col'ase. Generally, enzyme treatment tended to downregulate gene expression for major ECM markers, type I collagen (COL1), type II collagen (COL2), and aggrecan (ACAN) in the tissue adjacent to injection. However, chABC treatment induced an increase in COL2 gene expression, which was significant compared to the papain treated group. In general, papain and col'ase treatment tended to recapitulate aspects of advanced IVD degeneration, whereas chABC treatment captured aspects of early-stage degeneration. Chemonucleolysis of whole bovine IVDs is a useful tool providing researchers with a robust spectrum of degenerative changes and can be utilized for examination of therapeutic interventions.