Search

BACKGROUND In the developing brain, the death of immature oligodendrocytes (OLs) has been proposed to explain a developmental window for vulnerability to white matter injury (WMI). However, in neonatal mice, chronic sublethal intermittent hypoxia (IH) recapitulates the phenotype of diffuse WMI without affecting cellular viability. This work determines whether, in neonatal mice, a developmental window of WMI vulnerability exists in the absence of OLs lineage cellular death. METHODS Neonatal mice were exposed to cell-nonlethal early or late IH stress. The presence or absence of WMI phenotype in their adulthood was defined by the extent of sensorimotor deficit and diffuse cerebral hypomyelination. A separate cohort of mice was examined for markers of cellular degeneration and OLs maturation. RESULTS Compared to normoxic littermates, only mice exposed to early IH stress demonstrated arrested OLs maturation, diffuse cerebral hypomyelination, and sensorimotor deficit. No cellular death associated with IH was detected. CONCLUSIONS Neonatal sublethal IH recapitulates the phenotype of diffuse WMI only when IH stress coincides with the developmental stage of primary white matter myelination. This signifies a contribution of cell-nonlethal mechanisms in defining the developmental window of vulnerability to diffuse WMI. IMPACT The key message of our work is that the developmental window of vulnerability to the WMI driven by intermittent hypoxemia exists even in the absence of excessive OLs and other cells death. This is an important finding because the existence of the developmental window of vulnerability to WMI has been explained by a lethal-selective sensitivity of immature OLs to hypoxic and ischemic stress, which coincided with their differentiation. Thus, our study expands mechanistic explanation of a developmental window of sensitivity to WMI by showing the existence of cell-nonlethal pathways responsible for this biological phenomenon.

Given the important role of antioxidants in the cellular degeneration process, as well as the increased interest in recent years related to the use of natural antioxidants in therapy, the present study aims to investigate the antioxidant activity of a new pharmaceutical product containing natural antioxidants extracted from plant raw materials. In a first step, the product conventionally named “CILTAG”, containing a mixture in equal proportions of 10% hydroalcoholic extractive solutions of dried plant raw materials from Medicaginis herba, Trifolii pratense flores, Ginkgo bilobae folium, Myrtilli fructus, and Cynosbati fructus, was obtained. In the second stage, the antioxidant activity of the hydroalcoholic extractive solutions included in the pharmaceutical product was tested by chemiluminescence and electrochemical methods and by the superoxide dismutase (SOD) method. The electrochemical determination of the antioxidant capacity of hydroalcoholic extractive solutions was based on a method that provides an indirect evaluation of the presumed antioxidant properties of some compounds using Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), as a standard measurement. The experimental results indicate a significant antioxidant potential for both the analyzed plant extractive solutions that are part of CILTAG and the final product.

Neurodegenerative diseases are a group of conditions that affect neurons of the central nervous system characterised by progressive cellular degeneration and symptoms that significantly compromise the quality of life of patients and caretakers. Conventional treatments deal with obstacles such as the long course of the disease and the challenges of penetrating the blood–brain barrier. In the landscape of pharmaceutical research, scientists are driving their efforts towards the development of novel and efficient drug delivery systems. For an effective brain-targeting approach, several types of biodegradable nanoparticles are being exploited as promising delivery systems for drugs in the treatment of neurodegenerative diseases. While surface tailoring of nanoparticles with targeting moieties has been demonstrated to improve brain delivery, the nanoparticles need to be biodegradable, biocompatible and stable when sterilised. This chapter addresses the challenges encountered in the treatment of neurodegenerative diseases, namely, Alzheimer’s and Parkinson’s diseases, focussing on nanoparticles being developed for site-specific delivery of drugs to the brain and their sterilised production.

Background Cervicothoracic vertebral subluxation in sheep presents as a postural and locomotor disorder, and has been described in several breeds in Australia and overseas. Cervical myopathy may also be present in these cases. Case report A New South Wales sheep producer reported a postural and locomotor disorder with a low prevalence in his Poll Merino stud flock, affecting neonate, weaner and adult sheep. Animals with postural abnormalities, variable degrees of ataxia and proprioceptive deficits involving both fore and hind limbs were described. Abnormalities of the cervicothoracic vertebral column were identified grossly during necropsy, with misalignment and consequent narrowing of the posterior cervical spinal canal. Lesions ranging from pallor (cellular degeneration) to white streaky lesions with pinpoint haemorrhage (necrosis) were identified in the cervicothoracic paravertebral musculature of affected animals. Boney abnormalities were further characterised by imaging studies. Pedigree analysis of the very extensive breeding and disease incident records available for this flock suggested that the disease was inherited. A similar case recognised in a separate New South Wales Poll Merino flock is also described. Conclusion This report describes an entity of cervicothoracic vertebral subluxation in two Poll Merino sheep flocks, with cervical myopathy also identified in one, with preliminary evidence in the primary case that there is likely to be a hereditary basis. The two cases outlined in this report resemble the findings of several historical investigations into ovine flock postural disorders in Australia and beyond.

The view of mitochondria acting solely as a powerhouse of the cell is no longer accurate. Besides cell bioenergetics, primary targets of mitochondrial studies include their interplay with essential processes within the cell, including redox and calcium homeostasis, and apoptosis. Recent studies evidence the dynamic behavior of mitochondria, continuously moving, fusing, and dividing, and the interaction of these events with cellular degeneration and plasticity in neural cells. Our review summarizes novel data and technologies that are developed and applied to the identification and clarification of the mitochondrial role in neural plasticity using both cultured cells and in vivo approaches. The complete understanding and modulation of such mechanisms may represent a novel and promising therapeutic approach for treatment of diseases affecting central and peripheral nervous system.

Background. Promising studies have been conducted with many substances to reduce the ototoxic effects of cisplatin, but there is no treatment that completely eliminates the ototoxic effect. Objectives. To determine the effectiveness of astaxanthin (ASX) as a protective agent against cisplatin-induced ototoxicity. Materials and methods. Thirty-six rats were randomly divided into 6 groups. Group 1 received no drug injections except for anesthetics; group 2 received intraperitoneal (IP) olive oil only for 8 days; group 3 received only IP ASX 75 mg/kg dissolved in olive oil for 8 days; group 4 received a single dose of only IP 16 mg/kg cisplatin on the 5th day; group 5 received 25 mg/kg ASX IP daily for 8 days and a single 16 mg/kg dose of cisplatin on the 5th day; group 6 received 75 mg/kg ASX IP daily for 8 days and a single 16 mg/kg dose of cisplatin on the 5th day. The animals were tested for distortion product otoacoustic emissions (DPOAE) before and 3 days after cisplatin treatment. The animals in all groups were sacrificed under anesthesia on the 10th day. Before sacrifice, inferior vena cava blood samples were drawn into commercial tubes for biochemical analysis and their cochlea were prepared for histological analysis. Results. The ASX+cisplatin groups demonstrated significantly higher DPOAE thresholds when compared to the cisplatin-only group (p < 0.05). The ASX 25 mg/kg/day+cisplatin group showed a significant increase in total antioxidant capacity compared to the cisplatin-only group, whereas the ASX 75 mg/kg/day+cisplatin group had significantly lower total oxidative stress and oxidative stress index. Histologic results showed that the cortical organ was better preserved in the ASX+cisplatin groups compared to the cisplatin-only group, and the degeneration in the spiral ganglion and inner and outer hair cells was less visible in the ASX groups. Conclusions. Astaxanthin can protect hearing from cisplatin-induced ototoxicity, prevent cellular degeneration and significantly reduce oxidative stress.

Xanthomatous changes can be observed in various conditions including primary xanthomatosis that is linked to an underlying hypercholesterolemia and more commonly associated with secondary xanthomatous degenerative processes in neoplasm and chronic inflammation. Meningioma with extensive xanthomatous change is exceedingly rare. The presence of cholesterol clefts within this peculiar meningioma subtype has not been described. Herein, we report an unusual case of xanthomatous meningioma in an 83-year-old normolipidemic woman, who presented to us with worsening lower limb weakness and global aphasia. There was increasing evidence to suggest that the presence of xanthomatous changes in long-standing meningioma is merely a sequela of cellular degeneration rather than true metaplastic change as previously hypothesized. Hence, the diagnosis of "xanthomatous meningioma" in the metaplastic category should be revisited and considered as a distinct histological subtype. The possible histogenesis of such intriguing phenomenon is discussed with a review of the literature.

Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus (DM) causing vision impairment even at young ages. There are numerous mechanisms involved in its development such as inflammation and cellular degeneration leading to endothelial and neural damage. These mechanisms are interlinked thus worsening the diabetic retinopathy outcome. In this review, we propose oxidative stress as the focus point of this complication onset.

The study evaluated the effect of transportation over long distances on cattle muscle tissue of submitted to emergency slaughter in slaughterhouses in northern Tocantins, Brazil. The evaluations consisted in pH, muscle and liver glycogen, muscle histopathology and creatine kinase (CK), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity. Animals were placed into two groups: Experimental Group (EG), consisting of 19 bovines intended for immediate emergency slaughter, and Control Group (CG), composed of 24 bovines slaughtered in accordance with the normal flow. CK and ALT levels were high in EG. AST did not differ between groups. EG showed higher muscle pH and mean of degenerate fibers, mainly on the intercostal. However, muscle and liver glycogen did not differ between groups. In conclusion, cattle transported over long distances and subjected to immediate emergency slaughter showed markedly stress condition, with changes in biochemical parameters in the muscle tissue, determined by cellular degeneration. RESUMO O presente trabalho objetivou avaliar o efeito do transporte em longas distâncias sobre o tecido muscular de bovinos encaminhados ao abate de emergência. Foram avaliados pH, glicogênio muscular e hepático, análise histopatológica muscular, creatina quinase (CK), alanina aminotransferase (ALT) e aspartato aminotransferase (AST). Os animais foram alocados em dois grupos: grupo experimental (GE), constituído por 19 bovinos destinados ao abate de emergência, e grupo controle (GC), composto por 24 bovinos abatidos de acordo com o fluxo normal do frigorífico. A CK e a ALT estavam aumentadas no GE. O AST não diferiu entre os grupos. O GE apresentou maior percentual de fibras degeneradas, e o músculo intercostal teve maior quantidade de degenerações. O pH muscular foi superior no GE. O glicogênio muscular e o hepático não diferiram entre os grupos. Concluiu-se que bovinos encaminhados ao abate de emergência sofrem estresse severo pelo transporte por longas distâncias, com alterações bioquímicas no tecido muscular determinada pela degeneração celular.

Radiotherapy is a method of treatment used on malignant head and neck tumors; however, it may lead to adverse effects by influencing other tissues because its effects are not specific to tumor tissues. These adverse effects limit the effectiveness of the treatment and sometimes lead to termination of the treatment. This study aims to histopathologically and biochemically investigate the protective effect of whortleberry against the cellular degeneration and oxidative stress that take place in salivary glands due to radiotherapy. The rats were divided into 6 groups. One group was given radiotherapy only, one group was given radiotherapy and 100 mg/kg of whortleberry, and one group was given radiotherapy and 200 mg/kg of whortleberry. The remaining 3 groups were designated as whortleberry, sham, and control groups. At the end of the study, samples collected were histopathologically and biochemically analyzed. In the group given radiotherapy only, acinar areas were reduced histopathologically, whereas ductal areas increased ( P < .01). Oxidative stress increased only in the group given radiotherapy, whereas the oxidative stress levels in the other groups were close to those in the control groups. In conclusion, whortleberry reduces cellular degeneration and oxidative stress that take place in salivary glands due to radiotherapy.

Rationale In Duchenne muscular dystrophy (DMD), a genetic mutation results in a loss of dystrophin which leads to microtubular disorganization, cellular degeneration and muscle weakness. However, a...

Introduction: Ototoxicity has been defined as the tendency of certain therapeutic agents and other chemical substances to cause functional impairments and cellular degeneration of the tissues of the inner ear resulting in hearing loss. Objectives: This review is intended to provide details of a standardized preclinical assessment for ototoxicity under the current US FDA guidance documents that represents “industry best practices” for new drug application review of all new chemical entities being developed for human use. Methods: A literature review was conducted to assimilate study strategies that represent “Industry Best Practices” for the conduct of preclinical ototoxicity evaluation for submission to regulatory drug approval agencies. Conclusion: We have proposed a systems-approach and protocol criteria for the valid and reliable assessment of auditory function that can be easily included as a screening tool for ototoxicity within the Tiered Structure of preclinical assays required for approval of any chemical entity targeted for human use.

Protein misfolding due to mutation(s) and/or generation of unstable intermediate state(s) can be the cause of aberrant aggregations, leading to cellular degeneration. While molecular signatures like amyloidogenic regions cause aggregation, other features in proteins, like disorder and unique complexity regions, regulate and restrict such adhesive accumulation processes. Huntingtin interacting protein K (HYPK) is an aggregation-prone protein. Using various biophysical, microscopy, and computational techniques, we have deciphered how HYPK's N-terminal nanodisordered region plays a significant modulatory role in preventing its own aggregation and that of other proteins. HYPK's C-terminal hydrophobic regions lead to annular oligomerization and intermolecular charge interactions among the residues of low-complexity region (LCR) generate amorphous aggregates. The N-terminal disordered nanostructure loops toward the C-terminus, and a negative charge-rich patch in this region interacts with the LCR to shield LCR's positive charges. This interaction is required to prevent HYPK aggregation. Loss of this interaction causes partial unfolding of the structured C-terminus, resulting in HYPK's molten globule-like state and rapid annular oligomerization. The N-terminus also determines the specificity to mediate the differential bindings with aggregation-prone and wild type Huntingtin-exon1 proteins (Huntingtin97Q-exon1 and Huntingtin25Q-exon1). A sliding interaction of the specific N-terminal segment of HYPK along the extended polyglutamine region of Huntingtin-exon1 is responsible for HYPK's higher affinity for aggregation-prone Huntingtin than for its non-aggregating counterpart. Overall, our study provides evidence of the existence of disordered nanostructure in HYPK protein that mechanistically plays a decisive role in preventing both self and non-self protein aggregation.

The aim of the present study is to investigate the efficiency of colchicine in the experimental rat ovarian torsion model in the light of histological and biochemical data.A total of 35 Wistar albino female rats were randomly divided into 5 groups, group 1: (control-sham operated, n = 7); group 2: (torsion/detorsion, n = 7) 2 hours of ischemia and 2 hours of reperfusion; group 3: (torsion/detorsion, n = 7), 2 hours of ischemia and 5 days of reperfusion; group 4: (torsion/detorsion, n = 7) 2 hours of ischemia and 2 hours of reperfusion and a signal dose of oral 1 mL/kg colchicine; and group 5: (torsion/detorsion, n = 7), 2 hours of ischemia and 5 days of reperfusion and 5 days of oral 1 mg/kg colchicine. Histopathologic evaluation was performed by a scoring that assesses congestion, bleeding, edema, and cellular degeneration in the ovarian tissue. Catalase, tissue malondialdehyde (MDA), and protein carbonyl levels were calculated.The histopathologic scores, MDA, and protein carbonyl levels in the control and colchicine groups were significantly lower than groups 2 and 3 (P.001). Catalase activities were significantly higher in the control and colchicine groups than in groups 2 and 3 (P.001). The results of the histopathologic parameters and biochemical markers showed that protective effects of colchicine treatment persisted up to 5 days.Our study results revealed that colchicine reduced ovarian ischemia-reperfusion injury in experimental rat ovarian torsion model. As the ovarian detorsion is the first choice of the treatment modality in the early phase, antioxidant and anti-inflammatory treatment modalities like colchicine might be used to reduce ovarian ischemia-reperfusion injury.

Aims: This study assessed the neuroprotective effect of the aqueous extract of Garcinia kola on monosodium glutamateinduced toxicity in the cerebellar cortex of adult Wistar rats. Study Design: Twenty-five adult Wistar rats were randomly assigned into five groups (n=5): A, B, C, D, and E. Group A served as the control while the other groups served as the treated groups. Animals in group A were given feed and water liberally. Place and Duration of Study: This study was carried out in the Animal Holdings of the Department of Anatomy, Ladoke Akintola University of Technology Ogbomoso, Nigeria between September 2011 and December, 2011. Methodology: Animals in group B received 2.5 g/kg of monosodium glutamate orally for 14 days, Original Research Article Adeshina et al.; EJMP, 5(1): 13-22, 2015; Article no. EJMP.2015.002 14 group C received 200 mg/kg of Garcinia kola extract orally for 14 days, group D received 2.5 g/kg of monosodium glutamate and 200 mg/kg of Garcinia kola extract orally for 14 days and group E was pretreated with 200 mg/kg of Gracinia kola extracts orally for 14 days prior to the administration of 2.5 g/kg of monosodium glutamate for 14 days. The brain was excised and weighed before fixing in 10 % formal saline for histological processing. Results: The results reveal intact cerebellar neurons in group A, C and D. Group B reveals some cellular degeneration of cortical layers compared with other groups. Preservation of cerebellar tissue was observed in group B. Group E which was pretreated with Garcinia kola shows an appreciable preserved cerebellar tissue. Conclusion: This study concluded that Garcinia kola has protective effects on monosodium glutamate-induced cerebellar damage in adult Wistar rats.

La gestación en la perra transcurre entre la fecundación y el parto, y su duración tiene importancia clínica. La compleja biología de los gametos y embriones influye en la duración de la gestación, cuyo lapso fisiológico fluctúa entre los 57 y 70 días. Este amplio rango puede estar influenciado por los métodos referenciales para la estimación del inicio de la gestación. El realizar montas o inseminaciones en base a detección de la ovulación permite estrechar el rango a 62 a 64 días. Una condición de alto impacto obstétrico es la gestación de un solo cachorro, la cual es más prolongada y representa alto riesgo de distocia. Dada la importancia clínica de una adecuada proyección de la duración de la gestación y de la predicción de la fecha de parto, se han desarrollado fórmulas matemáticas para el cálculo de la edad fetal y tiempo al parto a través de la sistematización de la ultrasonografía gestacional., The purpose of the study was to describe and quantify cytological findings in the cat’s endometrium (Felis catus). Twenty genital tracts were obtained by ovariohysterectomy. To establish the status of the estrous cycle, vaginal cytology was evaluated and ovarian structures were recorded, resulting that all females were in the luteal phase. According to the presence of corpora lutea and follicles, a classification of the luteal phase was proposed: early diestrus: corpora lutea and follicles of 2 mm (n=3), mid-diestrus: corpora lutea without follicles (n= 4), and late diestrus: corpora lutea and follicles 0.5-1 mm (n=13). In the smears of the uterine mucosa, morphological patterns comparable to those described in the canine species were observed, emphasizing that it is possible to verify a decrease in the proportion of normal endometrial epithelial cells and an increase in cellular degeneration towards the final stage of the luteal phase (p

Present study reports post-ingestional effects of red chilli in stomach of house rat, Rattus rattus. Three different groups of female rats (5 per group) were fed on bait containing 1 and 2% red chilli powder and plain bait, respectively. Histomorphological study revealed cellular degeneration of gastric region, sloughing and distortion of superficial layer of epithelium and lymphocytic infiltration in the treated groups of rats. Histoenzymic study revealed an increase in AKPase and decrease in LDH, SDH, G-6-PD and GLD activities in glandular stomach of treated groups of rats. The present study revealed that the ingestion of red chilli powder causes gastric lesions and variation in the activity of alkaline phosphatase and oxidoreductases.

During endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), a needle is commonly used with a stylet, although recently the stylet has been omitted. This prospective study aimed to compare the quality of specimens obtained by EBUS-TBNA performed with and without a stylet. Between November 2013 and November 2014, 131 patients with lung cancer underwent EBUS-TBNA, with a total of 148 mediastinal or hilar lymph nodes sampled both with and without an inner-stylet, yielding 296 cytological specimens. Specimens were scored cytologically using five parameters: background blood or clot, amount of cellular material, degree of cellular degeneration, degree of cellular trauma, and retention of appropriate architecture. The procedure with a stylet required significantly longer operation time than without a stylet (14.5±0.8 vs 12.7±1.1 min, P

AIM: To compare the efficacy of fine – needle non – aspiration cytology (FNNAC) with that of fine – needle aspiration cytology (FNAC) of thyroid lesions. Materials and Methods: FNAC and FNNAC techniques were studied in 88 cases of thyroid lesions. All the needle – sampling procedures were done by a single operator. The samples were assessed cytologically and evaluated using five parameters, that is, background blood or clot, amount of cellular material, degree of cellular degeneration, and degree of cellular trauma and retention of appropriate architecture. Statistical Analysis: Wilcoxon signed rank test was performed using SPSS 14 software. Differences between all the individual parameters as observed in FNAC and FNNAC smears were insignificant. Results and Conclusion: After evaluation of FNAC and FNNAC on the basis of these scores, greater numbers of diagnostically superior samples were obtained by FNNAC; however, by FNAC more number of diagnostically adequate smears were observed. The numbers of unsuitable smears were also more by FNNAC technique.

Background: Differentiation between benign and malignant serous effusions always poses a great diagnostic dilemma. Differentiation often requires clinical findings, morphological evaluation and sometimes immunocytochemistry. Diagnostic possibility is enhanced if cell blocks are made along with the conventional cytology smears. This will help the clinicians in both treating the patient and determining the outcome of the disease process. Materials and methods: This hospital-based cross sectional analytical study was carried out in Department of Pathology in National Academy of Medical Sciences, Bir Hospital for one year. The objective of this study was to compare the smears cytology with cell blocks sections in serous effusions. Results: The four criteria scored for each technique were volume of background blood, amount of diagnostic cellular material, degree of cellular degeneration and trauma and architectural preservation. Background blood, amount of diagnostic material present and retention of architecture was more in cell block sections compared with smears cytology; whereas cellular degeneration and trauma was less appreciated in cell block sections which scored more than the smears cytology. Conclusion: Cell block preparation is simple, rapid and inexpensive technique for serous fluids in which malignant cells can be reliably detected thus avoiding unnecessary invasive procedure in patient management. DOI: http://dx.doi.org/10.3126/jpn.v3i6.8998 Journal of Pathology of Nepal (2013) Vol. 3, 482-486

Plant-derived natural products have made their own niche in the treatment of neurological diseases since time immemorial. Parkinson’s disease (PD), the second most prevalent neurodegenerative disorder, has no cure and the treatment available currently is symptomatic. This chapter thoughtfully and objectively assesses the scientific basis that supports the increasing use of these plant-derived natural products for the treatment of this chronic and progressive disorder. Proper considerations are made on the chemical nature, sources, preclinical tests and their validity, and mechanisms of behavioural or biochemical recovery observed following treatment with various plants derived natural products relevant to PD therapy. The scientific basis underlying the neuroprotective effect of 6 Ayurvedic herbs/formulations, 12 Chinese medicinal herbs/formulations, 33 other plants, and 5 plant-derived molecules have been judiciously examined emphasizing behavioral, cellular, or biochemical aspects of neuroprotection observed in the cellular or animal models of the disease. The molecular mechanisms triggered by these natural products to promote cell survivability and to reduce the risk of cellular degeneration have also been brought to light in this study. The study helped to reveal certain limitations in the scenario: lack of preclinical studies in all cases barring two; heavy dependence on in vitro test systems; singular animal or cellular model to establish any therapeutic potential of drugs. This strongly warrants further studies so as to reproduce and confirm these reported effects. However, the current literature offers scientific credence to traditionally used plant-derived natural products for the treatment of PD.

The development of new treatments for stroke remains a formidable challenge as emphasized in the article by Frank Sharp and colleagues [1]. However, with the recent advances in genomic and proteomic profiling [2–4], in vitro screening methodologies [5–7], predictive animal models [8–12], and a greater understanding of the complexity of processes and mechanisms involved in cellular degeneration and behavioral deficits following a stroke [13,14], we now have the basic tools in our repertoire to develop and systematically test new candidates in a preclinical translational setting. Moreover, with more sophisticated adaptive clinical trial design [15–18], therapy can be targeted to specific stroke patient populations to ensure some extent of efficacy, rather than complete failure. If the best that we can expect to achieve is to treat some patients, then we should accept that fact!

Background: While Helicobacter pylori exists in a bacillary form in both the natural habitat and the human host, detrimental environmental circumstances have been observed to lead to the conversion of H. pylori from the bacillary to the coccoid form. However, the viability or nonviability of coccoid forms remains to be established in H. pylori. The aim of this study was to determine whether the quantitative PCR combined with propidium monoazide could be an alternative and good technique to determine H. pylori viability in environmental samples and, to contribute to understanding of the role of the H. pylori forms. Materials and Methods: Viability, morphological distribution, and the number of live H. pylori cells were determined using a propidium monoazide-based quantitative PCR method, at various time points. Results: Under adverse environmental conditions was observed the conversion of H. pylori from the bacillary to the coccoid form, and the decrease in amplification signal, in samples that were treated with propidium monoazide, over the time. Conclusions: Incorporation of propidium monoazide indicates that there is an increase in H. pylori cells with the damaged membrane over the study, leading to the manifestation of cellular degeneration and death. Consequently, quantitative PCR combined with propidium monoazide contributes to our understanding of the role of H. pylori cells, under adverse environmental conditions.

Summary The ultrastructure of the crops of chickens maintained on an experimental diet deficient in zinc is described. In the stratum basale and especially the stratum spinosum there were reduced numbers of desmosomes, desmosomal filaments, tonofilaments and membrane-coating granules; the intercellular spaces were distended. Ribosomes were less numerous in severely affected prickle cells, in which there was cytoplasmic vesiculation and cellular degeneration. Heterophil infiltration was present. The nuclei and nucleoli of the epithelial cells were enlarged. Enlargement and ring-shaped appearance of the nucleolus and atypical morphology of its fibrillar and nucleolonemal components were very prominent; these phenomena are discussed in relation to the effects of zinc deficiency on nucleic acid and protein synthesis. Zusammenfassung Die Ultrastruktur des Kropfes bei Kuken mit Zinkmangel Bei Kucken mit experimentellem Zinkmangel wird die Ultrastruktur des Kropfes beschrieben. Im Stratum basale und speziell im Stratum spinosum wurde eine reduzierte Anzahl von Desmosomen, desmosomalen Filamenten, Tonofilamenten und membrangebundenen Granula gefunden. Die Interzellularraume waren erweitert. Stark affizierte Stachelzellen enthielten weniger Ribosomen, zudem zeigten diese Zellen eine zytoplasmatische Vesikulation und Degenerationserscheinungen. Auch wurden heterophile Infiltrate gefunden. Die Kerne und Kernkorperchen der Epithelzellen waren vergrosert. Auffallig waren ringformige Nukleolen mit einer atypischen Struktur der fibrillaren und nukleolonemalen Komponenten. Diese Erscheinungen werden als Einflus des Zinkmangels auf die Synthese der Nucleinsauren- und Protein-synthese diskutiert. Resume L'ultrastructure du jabot chez des poussins carences en zinc L'ultrastructure du jabot est decrite chez des poussins experimentalement carences en zinc. On a trouve un nombre reduit de desmosomes, de filaments desmosomaux, de tonofilaments et de granulations liees a la membrane dans Stratum basale et specialement dans Stratum spinosum. Les espaces intercellulaires etaient elargis. Les elements de la couche filamenteuse fortement atteints contenaient moins de ribosomes et ces cellules presentaient une vesicule cytoplasmique et des signes de degenerescente. Des infiltrations heterophiles furent egalement trouvees. Les noyaux et nucleoles des cellules epitheliales etaient grossais. Des nucleoles en forme d'anneau avec une structure atypique des composants fibrillaires et «nucleolonemaux» furent frappants. Ces observations sont discutees en fonction de l'influence de la carence en zinc sur la synthese des acides nucleiques et des proteines. Resumen La ultraestructura del buche en pollitos con deficiencia de cinc Se describe la ultraestructura del buche en pollitos con deficiencia experimental de cinc. En el estrato basal y especialmente en el estrato espinoso se hallo una cantidad reducida de desmosomas, filamentos desmosomales, tonofilamentos y granulos que revisten a las membranas. Los espacios intercelulares se encontraban distendidos. Las celulas espinosas muy afectadas contenian menos ribosomas; las mismas celulas mostraban una vesiculacion citoplasmatica y manifestaciones degenerativas. Tambien se hallaron infiltraciones heterofilas. Los nucleos y nucleolos de las celulas epiteliales se encontraban agrandados. Eran muy prominentes los nucleolos anulares con una estructura atipica de los componentes fibrilares y nucleolonemales. Se discuten estos fenomenos en relacion con los efectos de la deficiencia de cinc sobre la sintesis de los acidos nucleicos y de las proteinas.

Polyglutamine pathologies are neurodegenerative diseases that manifest both general polyglutamine toxicity and mutant protein-specific effects. Dentatorubral-pallidoluysian Atrophy (DRPLA) is one of these disorders caused by mutations in the Atrophin-1 protein. We have generated several models for DRPLA in Drosophila and analysed the mechanisms of cellular and organism toxicity. Our genetic and ultrastructural analysis of neurodegeneration suggests that autophagy may have a role in cellular degeneration when polyglutamine proteins are overexpressed in neuronal and glial cells. Clearance of autophagic organelles is blocked at the lysosomal level after correct fusion between autophagosomes and lysosomes. This leads to accumulation of autofluorescent pigments and proteinaceous residues usually degraded by the autophagy-lysosome system. Under these circumstances, further pharmacological and genetic induction of autophagy does not rescue neurodegeneration by polyglutamine Atrophins, in contrast to many other neurodegenerative conditions. Our data thus provide a crucial insight into the specific mechanism of a polyglutamine disease and reveal important differences in the role of autophagy with respect to other diseases of the same family.

Amyloidogenesis defines a condition in which a soluble and innocuous protein turns to insoluble protein aggregates known as amyloid fibrils. This protein suprastructure derived via chemically specific molecular self-assembly process has been commonly observed in various neurodegenerative disorders such as Alzheimer's, Parkinson's, and Prion diseases. Although the major culprit for the cellular degeneration in the diseases remains unsettled, amyloidogenesis is considered to be etiologically involved. Recent recognition of fibrillar polymorphism observed mostly from in vitro amyloidogeneses may indicate that multiple mechanisms for the amyloid fibril formation would be operated. Nucleation-dependent fibrillation is the prevalent model for assessing the self-assembly process. Following thermodynamically unfavorable seed formation, monomeric polypeptides bind to the seeds by exerting structural adjustments to the template, which leads to accelerated amyloid fibril formation. In this review, we propose another in vitro model of amyloidogenesis named double-concerted fibrillation. Here, two consecutive assembly processes of monomers and subsequent oligomeric species are responsible for the amyloid fibril formation of alpha-synuclein, a pathological component of Parkinson's disease, following structural rearrangement within the oligomers which then act as a growing unit for the fibrillation. [BMB reports 2009; 42(9): 541-551].

To evaluate the protective effect of intravesical oxybutynin on the ultrastructure of rabbits with detrusor overactivity (DO). Seventeen North Folk male rabbits were distributed into three groups: GI (n = 5) used as control, GII (n = 5), and GIII (n = 5) with DO. One animal from GII and one from GIII were excluded because they did not develop DO. In GIII, the animals were treated with daily intravesical application of 0.5 mg/Kg of oxybutynin for 30 days. Bladder weight was significantly higher in animals from GII and GIII as compared to GI. After 30 days, cystometric study revealed that vesical capacity was significantly decreased in GII and GIII. Detrusor pressure was significantly higher in GII. Electron microscopy showed increase of intercellular space, cell junctions and caveolae areas asymmetries, mitochondria and cellular degeneration in GII, while in GIII, these alterations have improved after a 30-day treatment. Animals treated with intravesical oxybutynin presented ultrastructural aspect similar to normal.

A restorative therapy for a disease such as Parkinson's, where substantial cellular degeneration has already occurred at the time of diagnosis, is likely to require a more complex intervention than simply enhancing dopamine output in the brain. Here we assess the value and feasibility of a variety of strategies aimed at either replacing the lost neuronal circuitry or providing one-off delivery of corrective and/or neuroprotective genes.

Many studies have shown that apoptotic cell death occurs at an increased rate in osteoarthritic cartilage. Whichever type of cell death takes places in articular cartilage, it is important to prevent, because it is detrimental to articular cartilage maintenance. Thus, it is important to characterize events going on during cellular degeneration in more detail. Overall, physicians have reached a reasonable level of understanding of the extent of cell death occurring in the disease process, but they are still at an early stage in the understanding of the mechanisms underlying this process and the means of intervening in this facet of cartilage destruction.

Introduction: Fine needle aspiration (FNA) has been adopted as a simple and cost effective technique for cytologic studies of thyroid nodules. The recently introduced fine needle nonaspiration (FNNA) technique, however, is claimed to be superior because it provides specimens with larger number of cells and better preserved cytomorphology and architecture of thyroid papillae and follicles. In this study, we compare the efficacy of the two methods. Materials and Methods: Two hundred patients with thyroid nodules, 1–4 cm in size, were recruited. FNA and FNNA techniques were applied to each patient. In a single-blind setting, all specimens were examined by a single cytopathologist. The specimens were scored (0, 1, or 2) on the basis of background blood or clot, number of obtained cells, preserved architecture of papillae and follicles, and cellular degeneration. Nonparameteric methods were then used to compare the scores of the two techniques. Results: Two hundred patients (162 female, 38 male) were entered into the study. Specimens from 43 patients were inadequate. In the remaining 157 patients, no statistically significant difference was seen between FNNA and FNA average scores in each parameter (p>0.05). Conclusion: We concluded that FNNA is not superior to FNA in the cytopathologic studies of thyroid nodules.

The dermal toxicity due to industrial chemicals is well recognised. They may be the cause of skin irritation and skin sensitization. Some of the chemicals may result in dermal reactions such as changes in skinfold thickness, cellular degeneration and necrosis. The absorption through the skin may also cause penetration of chemicals into the organism causing systemic effects.

Background: Podocyte injury and loss, caused by a variety of insults, is a common and determining factor for the progression of glomerular diseases. Being postmitotic and highly differentiated, podocytes have no or a very limited ability to proliferate or regenerate. Thus, understanding the mechanisms that help maintain and defend podocytes is of great importance. Autophagy is a cellular process by which cytoplasmic cargos are sequestered within autophagosomes and then delivered to lysosomes for degradation and turnover. Recent research has highlighted an important role of autophagy in the maintenance of cellular homeostasis under physiological and pathological conditions. Summary: A high basal level of autophagy is a characteristic hallmark of differentiated podocytes, which may contribute critically to the structural and functional integrity of the cells. Autophagy is also essential for long-term podocyte homeostasis in aging, protecting podocytes against cellular degeneration and age-related kidney diseases. In glomerular diseases, alteration of autophagic activity may be an adaptive and protective mechanism against podocyte injury and disease progression. Recent studies have further suggested an intriguing and unique interplay between mTOR signaling and autophagy in podocytes. Key Messages: Altogether, these findings unveil an emerging role of autophagy in the physiology and pathology of podocytes. Further work should elucidate the regulatory mechanism of autophagy in podocytes, determine its pathophysiological role in various kidney diseases, and test autophagy-targeting therapies.

Conceptually and from a practical standpoint, bone marrow has been the most influential source of stem cells that offers a possibility of being used in a wide range of therapeutics. Clinical situations frequently demand stem cells with dependable quality and quantity to treat disorders of cellular degeneration. Challenges to bring advances to the clinical mount have expanded rapidly, engendering new perspectives concerning the identity, origin, and full therapeutic potential of various tissue-specific stem cells. Recent progress in stem cell biology has allowed researchers to investigate distinct stem cell populations in such divergent mammalian tissues and organs. Taking stem cells adaptable for regenerative medicine applications in adequate quantities at the right time is a challenge. In this respect, an emerging body of literature suggests that redundant adipose tissue serves as an abundant, accessible, and reliable source of stem cells that can be readily harvested with minimal risk to the patients. Rapidly accumulating evidence suggests that adipose tissue-derived stem cells (ADSC), especially from white adipose tissue, possess a far wider property of self-renewal and multilineage differentiation capacity, thereby highlighting their importance and effectiveness in regenerative medicine [1–5]. Despite literature supporting the capacity and plasticity of ADSC for regenerative medicine, there are functional and heterogeneous discrepancies associated with it, thus presenting ADSC research a difficult and challenging task. Promising strides are continuously being made to unravel these challenges and realize the potential of ADSC. While much progress on adipose-derived stem cells has been made in the last few years, there remain a lot to be explored.

A hipóxia-isquemia (HI) encefálica neonatal causa diversas seqüelas motoras e cognitivas permanentes devido à grande degeneração celular que ocorre no encéfalo dos neonatos. Esse dano é progressivo e gera atrofias visíveis em diversas estruturas encefálicas, principalmente hipocampo, estriado e córtex cerebral. Um estudo recente do nosso grupo de pesquisa mostrou que o tratamento com ácido fólico (AF) reverteu o déficit cognitivo e a diminuição da atividade da enzima Na+, K+-ATPase, em ratos submetidos à HI neonatal. Assim, buscando compreender melhor a possível eficácia do ácido fólico em tratar e/ou prevenir o dano causado pela HI neonatal, o objetivo desse estudo foi avaliar os efeitos do tratamento com ácido fólico na degeneração celular na região CA1 do hipocampo dorsal 24 horas após o evento lesivo e em diferentes marcos do desenvolvimento de animais submetidos à hipóxia-isquemia neonatal. Foram utilizados ratos Wistar de ambos os sexos que foram submetidos ao modelo de Levine-Rice no 7º dia de vida pós-natal, sendo divididos em quatro grupos experimentais: 1) controle tratado com salina (CTS); 2) controle tratado com ácido fólico (CTAF); 3) HI tratado com salina (HIS); 4) HI tratado com ácido fólico (HIAF). Os animais receberam uma dose intraperitoneal de AF (0,011 μmol/g de peso corporal) 24 horas antes, imediatamente antes e 24 horas após a HI ou, diariamente, até o 14° DPN. Não foram encontradas diferenças na quantificação de células imunomarcadas para caspase-3 clivada pela técnica de imunoistoquímica, porém na avaliação da densidade celular observou-se uma diminuição de células no grupo HIS 13 quando comparado com os grupos CTAF e HIAF no hipocampo direito. Tanto na análise qualitativa quanto quantitativa da ultraestrutura dos neurônios piramidais da região CA1 hipocampal também foi possível encontrar uma importante degeneração celular nos grupos submetidos à HI neonatal, predominantemente caracterizada pelo padrão necrótico, porém no grupo tratado com AF essa degeneração foi menos expressiva. Quanto aos marcos do desenvolvimento, não verificou-se diferença nem pela lesão nem pelo tratamento. A partir desse estudo, portanto, podemos concluir que 24h após a HI ocorre diminuição da densidade celular e evidente processo lesivo ao tecido hipocampal, mais expressivamente por necrose. Ainda, a suplementação com ácido fólico foi capaz de reduzir e/ou prevenir o dano celular na região CA1 do hipocampo ipsilateral à oclusão arterial. Neonatal hypoxia-ischemia (HI) causes diverse permanent motor and cognitive sequelae due to extensive cellular degeneration that occurs in the brain of neonates. This damage is progressive and generates visible atrophy in several brain structures, particularly the hippocampus, cerebral cortex and striatum. A recent study from our research group demonstrated that treatment with folic acid (FA) reversed cognitive deficits and decreased activity of the enzyme Na+, K+-ATPase in rats submitted to neonatal HI. Thus, in order to better understand the possible effectiveness of folic acid in recovering and / or preventing the damage caused by neonatal HI, the aim of this study was to evaluate the effects of treatment with folic acid on cell degeneration in the CA1 region of the dorsal hippocampus 24 hours after neonatal hypoxia-ischemia and at different developmental milestones of animals submitted to neonatal hypoxia-ischemia. Wistar rats of both sexes were submitted to the Levine - Rice model on the 7th postnatal day, being divided into four experimental groups: 1) control treated with saline (CTS); 2) control treated with folic acid (CTAF); 3) HI treated with saline (HIS) 4) HI treated with folic acid (HIAF). Animals received an intraperitoneal dose of FA (0.011μmol/g of body weight) 24 hours before, immediately before and 24 hours after the HI. No differences were found in the quantification of positive cells for cleaved caspase-3 by immunohistochemistry, but in the assessment of cell density was observed a decrease of cells in the HIS group when compared with the CTFA and HIFA groups in the right hippocampus. In the analysis of the ultrastructure of pyramidal neurons of the 15 hippocampal CA1 region was also possible to find an important cellular degeneration in the groups subjected to neonatal HI, predominantly characterized by necrotic pattern, but in the group treated with FA this degeneration was less expressive. As for developmental milestones, no significant difference was observed either by injury or by treatment. Concluding, 24 hours after HI occurs decreased cell density and evident degeneration process to hippocampal tissue, most significantly with death by necrosis. Yet, supplementation with folic acid was able to reduce and / or prevent cell damage in the CA1 region of the hippocampus ipsilateral to the arterial occlusion.

In the case of an asymptomatic 10-year-old girl with neurofibromatosis type 1, a concomitant cystic brain lesion was demonstrated on cranial magnetic resonance imaging. The nature of these cysts is unknown: they may represent cellular degeneration of the lesions imaged as unidentified bright objects, cystic cortical dysplasia, or giant Virchow-Robin spaces. The novel finding in this child of coexisting unusual cystic lesion and neurofibromatosis could be coincidental; however, recent report of an asymptomatic cystic lesion in two patients with neurofibromatosis suggests otherwise.

The anatomy of the vascular cylinders of 150-mm-long pea primary roots (Pisum sativum cv Alaska) grown at 10° and 25°C was examined by light and electron microscopy. Root and vascular cylinder diameters were greater at 10°C. At maturity vascular cylinder cells were longer at 10°C than at 25°C, but did not differ in mean diameter (11-16 μm). This effect was most pronounced in the xylem sectors (626 vs. 429 μm). Observation of cell ultrastructure showed cellular degeneration in some central xylem cells at both temperatures in the region 20-24 mm from the root tip, but degeneration was more extensive at 25°C. The ultrastructure of degenerating cells was similar to that of senescing cells. At 25°C, within the region 25-29 mm from the tip, expanding metaxylem tracheary elements (MTEs) appeared to cause pressure on surrounding cells. This stress appeared to disrupt walls of degenerating cells, leading to the formation of small lacunae in the region 30-34 mm from the root tip. The lacunae expanded by similar lys...

The main problem of tremor is the damage caused to the quality of the life of patients, especially those at more advanced ages. There is not a consensus yet about the origins of this disorder, but it can be examined in the correlations between the biological signs of aging and the tremor characteristics. This work sought correlations between the osmotic fragility of erythrocytes and features extracted from electromyographic (EMG) activity resulting from physiological tremor in healthy patients (N=44) at different age groups (24-87 years). The osmotic fragility was spectrophotometrically evaluated by the dependence of hemolysis, provided by the absorbance in 540 nm (A 540 ), on the concentration of NaCl. The data were adjusted to curves of sigmoidal regression and characterized by the half transition point (H 50 ), amplitude of lysis transition ( dx ) and values of A 540 in the curve regions that characterize the presence of lysed (A 1 ) and preserved erythrocytes (A 2 ). The approximate entropy was estimated from EMG signals detected from the extensor carpi ulnaris muscle during the movement of the hand of subjects holding up a laser pen towards an Archimedes spiral, fixed in a whiteboard, and from an acelerometer fixed at the pen. The evaluations were carried out with the laser pen at rest, at the center of the spiral, and in movement from the center to the outside and from outside to the center. The correlations among the parameters of osmotic fragility, tremor, gender and age were tested. Negative correlations with age were found for A 1 and dx. With the hand at rest, a positive correlation with H 50 was found for the approximate entropy. Negative correlations with H 50 were found for the entropy with the hand in movement, as from the center to the outside or from the outside to the center of the spiral. In neurological healthy individuals, the increase in the erythrocyte osmotic fragility was associated with a decrease in the approximate entropy for rest tremor and with an increase of the entropy for movement tremor. This suggests that the neuromuscular degeneration associated with tremor entails also the mechanisms involved in the breakdown of structural homeostasis of the erythrocyte membrane.

Human diseases involving protein misfolding and aggregation have received increasing attention in recent years. Alzheimer’s disease and other diseases associated with aging are sweeping the developed countries whose populations are rapidly aging. Recent progress has improved our knowledge about molecular and cellular pathogenesis of these diseases. For more than 20 years, multiple diseases such as Alzheimer’s and Parkinson’s diseases have been associated with accumulation of abnormal protein fibrils. These self-assembling fibrils, referred as “amyloid,” have been considered the pathogenic molecules that cause cellular degeneration. Accumulation of fibrillar Aβ in plaques underlies the theory for Alzheimer’s disease. Recent experiments have provided evidence that fibrils are not the only neurotoxins. Soluble oligomers and protofibrils play a crucial role in causing cellular dysfunction and death. These oligomers, the missing links in the original amyloid cascade hypothesis, have been incorporated into an updated amyloid cascade. Despite new information gained, there is no disease-modifying treatment. New insights into disease mechanisms and new therapeutic strategies give hope for change.

TRP channels participate in many cellular processes including cell death. These channels mediate these effects mainly by changing the cellular concentration of Ca(2+), a prominent cellular second messenger. Measuring the current-voltage relationship and state of activation of TRP channels is of utmost importance for evaluating their contribution to a cellular process within a spatial and temporal context. The study of TRP channels and characterization of their mode of activation will benefit and progress our understanding of each channel's role in specific cellular mechanisms. Many TRP channels exhibit constitutive activity, which is mostly observed in cell-based expression systems. This constitutive activity can lead, in many cases, to cellular degeneration, which can be readily observed morphologically and by biochemical assays. This chapter describes in brief different modes of TRP channel activity and their current-voltage relationships. The chapter outlines methods for visualizing this activity and methods to correlate between TRP channel activity and cell death, and it illustrates mechanisms that prevent cell death in spite of constitutive activity. Finally, it describes methods for qualitatively and quantitatively measuring the accompanied cellular degeneration.

Multiple diseases, as diverse as diabetes and mad cow disease, exhibit accumulations of abnormal protein fibrils. Generically referred to as “amyloid,” these self-assembling fibrils typically have been considered the pathogenic molecules that cause cellular degeneration (toxins, not just tombstones). A prominent example is the “amyloid cascade hypothesis” proposed for Alzheimer’s disease (Hardy and Higgins, 1992). Fibrils, however, are not the only toxins generated by protein self-association, probably in some cases not even the most relevant ones. We now know of toxic subfibrillar species—soluble oligomers and protofibrils. The emerging hypothesis considered here is that these novel subfibrillar assemblies, the hidden toxins, constitute significant pathogenic molecules in diseases of fibrillogenic proteins.

The effects on morphology and diagnostic interpretation of delayed processing of refrigerated effusion samples have not been well documented. The potential for cellular degeneration has led many laboratories to reflexively fix samples rather than submit fresh/refrigerated samples for cytologic examination. We sought to determine if effusion specimens are suitable for morphologic, immunocytochemical, and DNA-based molecular studies after prolonged periods of refrigerated storage time. Ten fresh effusion specimens were refrigerated at 4 degrees C; aliquots were processed at specific points in time (days 0, 3, 5, 7, 10, 14). Specimens evaluated included four pleural (3 benign, 1 breast adenocarcinoma) and six peritoneal (2 ovarian adenocarcinomas, 1 malignant melanoma, 2 mesotheliomas, 1 atypical mesothelial) effusions. The morphology of the cytologic preparations from the 10 effusions was preserved and interpretable after 14 days of storage at 4 degrees C. The immunocytochemical profile of the samples (AE1/AE3, EMA, calretinin, and LCA) was consistent from day 0 to day 14. Amplifiable DNA was present in all samples tested on day 14. We conclude that cytopathologic interpretation of effusion samples remains reliable with refrigeration at 4 degrees C even if processing is delayed.