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Neuromyelitis optica is an autoimmune inflammatory disorder targeting aquaporin-4 water channels in CNS astrocytes. Histopathological descriptions of astrocytic lesions reported in neuromyelitis optica so far have emphasized a characteristic loss of aquaporin-4, with deposition of IgG and complement and lysis of astrocytes, but sublytic reactions have been underappreciated. We performed a multi-modality study of 23 neuromyelitis optica autopsy cases (clinically and/or pathologically confirmed; 337 tissue blocks). By evaluating astrocytic morphology, immunohistochemistry and AQP4 RNA transcripts, and their associations with demyelinating activity, we documented a spectrum of astrocytopathy in addition to complement deposition, microglial reaction, granulocyte infiltration and regenerating activity. Within advanced demyelinating lesions, and in periplaque areas, there was remarkable hypertrophic astrogliosis, more subtle than astrocytic lysis. A degenerative component was suggested by ‘dystrophic’ morphology, cytoplasmic vacuolation, Rosenthal fibres and associated stress protein markers. The abundance of AQP4 mRNA transcripts in sublytic reactive astrocytes devoid of aquaporin-4 protein supported in vivo restoration following IgG-induced aquaporin-4 endocytosis/degradation. Astrocytic alterations extending beyond demyelinating lesions speak to astrocytopathy being an early and primary event in the evolving neuromyelitis optica lesion. Focal astrocytopathy observed without aquaporin-4 loss or lytic complement component deposition verifies that astrocytic reactions in neuromyelitis optica are not solely dependent on IgG-mediated aquaporin-4 loss or lysis by complement or by IgG-dependent leucocyte mediators. We conclude that neuromyelitis optica reflects a global astrocytopathy, initiated by binding of IgG to aquaporin-4 and not simply definable by demyelination and astrocytic lysis. The spectrum of astrocytic morphological changes in neuromyelitis optica attests to the complexity of factors influencing the range of astrocytic physiological responses to a targeted attack by aquaporin-4-specific IgG. Sublytic astrocytic reactions are no doubt an important determinant of the lesion’s evolution and potential for repair. Pharmacological manipulation of the astrocytic stress response may offer new avenues for therapeutic intervention.

Iridovirus infection has threatened the aquaculture industry worldwide. It has been associated with severe disease and economic losses in fish. In the present study, sixty-two fishes (Sea bream = 50; Sea bass = 3; Mullet = 9) were collected from Damietta and Sharkia Governorates, Egypt during May 2019-September 2020. The clinical signs, gross lesions and histopathological findings were recorded and later confirmed by molecular detection of Iridovirus in different fish species. Besides, isolation of molecularly identified Iridovirus from fish tissues in Vero cell cultures was done. Clinically, the affected fishes become lethargic, exhibit severe anemia, petechiae in the skin and gills. Unilateral hemorrhages in eye and cloudy eye were recorded only in Sea bream fish. Necropsy of the infected fishes revealed congestion of the internal organs, petechial hemorrhages on spleen, liver, kidneys and heart. Necrotic foci on liver were also observed. Histopathological examination revealed congestion of portal veins, cytoplasmic vacuolation with presence of intranuclear eosinophilic inclusion bodies within degenerated hepatocytes. Multifocal necrosis and various degree of inflammation in different fish tissues were observed. Molecularly, the obtained 1000 bp amplicon by PCR confirmed the presence of Iridovirus major capsid protein (MCP) gene with a percentage of 12.1%. It was detected in both fry and market size fish as well as in clinically infected and apparently healthy fish. The molecularly identified virus was able to replicate in Vero cells at 28oC, but not at 37 oC. To our knowledge, this is the first report of Iridovirus isolation in Vero cells and detection in fish within Damietta and Sharkia Governorates, Egypt. Further studies are recommended to investigate its presence on a broader scale with genomic sequence analysis.

Objectives: The post-mortem interval (PMI) refers to the amount of time elapsed between death and discovery of the body. This study aimed to evaluate light microscopic cellular changes in the oral mucosa and identify the potential of this method for predicting PMI. Methods: This prospective study was conducted between July 2016 and January 2018 at the Institute of Dental Sciences, Siksha ‘O’ Anusandhan University, Bhubaneswar, India. A total of 150 post-mortem (including 75 gingival and 75 buccal mucosa samples) and 40 ante-mortem (including 20 gingival and 20 buccal mucosa samples) tissue samples were compared using haematoxylin and eosin, periodic acid-Schiff (PAS) and van Gieson stains. Microscopic changes in the epithelium and connective tissue were categorised according to PMI stage as early (20.5 hours since death). Results: Most epithelial cellular changes occurred early, except for arc-shaped nuclei and epithelial shredding which were intermediate and late changes, respectively. However, microscopic changes in the connective tissue were only observable at ≥12.5 hours. There was a progressive decrease in intensity in van Gieson stains and an increase in intensity in PAS stains as PMI increased. Several microscopic features were found to be significant predictors of PMI including epithelial homogenisation, cytoplasmic vacuolation, nuclear degeneration, arc-shaped nuclei, chromatin clumping, red blood cell clumping and lysis, melanin incontinency, myofibril degeneration, salivary gland acini degeneration and epithelial connective tissue separation (P

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly-described adult-onset inflammatory syndrome characterized by vacuoles in myeloid and erythroid precursor cells and somatic mutations affecting methionine-41 (p.Met41) in UBA1. The VEXAS syndrome often overlaps with myelodysplastic syndromes (MDS) with autoimmune disorders (AD). By screening the UBA1 gene sequences derived from MDS patients with AD from our center, we identified one patient with a p.Met41Leu missense mutation in UBA1, who should have been diagnosed as MDS comorbid with VEXAS syndrome. This patient respond poorly to immune suppressive drugs. Patients with MDS and AD who have characteristic vacuoles in myeloid and erythroid precursor cells should be screened for UBA1 mutation, these patients are likely to have VEXAS syndrome and unlikely to improve with immunosuppressive drugs and should be considered for other alternative therapies.

Introduction: Polychlorinated biphenyl (PCB) is considered one of the environmental pollutants. It is used as hydraulic coils in vacuum pumps, pesticides transformers, heat-exchange systems, capacitors and as additives in adhesive inks, paints, plastics, copying paper and sealants. Alpha lipoic acid (ALA) is an antioxidant substance normally present in mitochondria as a coenzyme. Aim of the Work: To evaluate the protective effect of ALA on PCB induced testicular toxicity. Materials and Methods: Twenty five adult male albino rats were used in this study. They were divided into four groups, a control group included 10 rats, group II rats received alpha lipoic acid 25mg/Kg /day orally for 30 days, group III rats received PCB 5mg /Kg/day orally for 30 days and group IV rats received both PCB and alpha lipoic acid at the same previous dose for 30 days. At the appropriate time, the specimens were taken and prepared for light and electron microscope study. Results: LM examination revealed structural alterations in group III in the form of wide spaces between seminiferous tubules that contain homogeneous acidophilic substance, partial or complete detachment of the tubules from the basement membrane and total distorted irregular shaped tubules. Also dilated congested blood vessels were seen. EM examination of this group revealed Sertoli cells with cytoplasmic vacuolation and dilated rER. The basement membrane appeared as thick and irregular line under Sertoli and spermatogenic cells and it was interrupted in some points. Primary spermatocyte appeared shrunken while others revealed vacuoles in the cytoplasm and perinuclear dilatation. Leydig cells showed irregular vacuoles and swollen destroyed mitochondria. Amelioration of the previous histological changes could be detected in group IV. Conclusion: It could be concluded that alpha-lipoic acid has a protective effect against PCB induced testicular toxicity.

Introduction: Carbimazole is used in the treatment of hyperthyroidism. Parsley is a common herb used in various types of industries such as food, cosmetics, and pharmaceuticals.Aim of the study: The current experiment is aimed to assess the harmful effect of carbimazole on the exocrine part of the pancreas of adult male albino rats and to analyze the protective role of parsley extract. Material and methods: twenty-eight rats were used and divided equally into control group, parsley group that was administered 1 ml of parsley extract /150 g/day for 8 weeks, carbimazole group that was treated with 1.35 mg of carbimazole/Kg/day for 8 weeks, and carbimazole and parsley extract-treated group that received both carbimazole and parsley extract in the same doses and durations as the previous groups. The pancreatic specimens were dissected out and prepared for light and electron microscopic examination.Results: Carbimazole induced clear histopathological alterations in the rat pancreas compared to the control group. There was degeneration in the epithelial cells of pancreatic acini with cytoplasmic vacuolation and a marked decrease in apical acidophilia. Widening in the intercellular space with mononuclear cellular infiltration and blood vessel congestion were also noticed. Morphological analysis showed a significant increase in collagen fibers in-between the pancreatic acini, around the blood vessels, and the interlobular ducts. Ultrastructure analysis also revealed dilatation in the rough endoplasmic reticulum, ballooning mitochondria with disturbed cristae as well as less electron-dense secretory granules. However, carbimazole and parsley extract co-treated showed major improvement in the histology and ultrastructure of pancreatic tissue.In conclusion: the results verified the protective role of parsley against the toxic effect of carbimazole which could belong to the antioxidant properties of parsley.KeywordsCarbimazole; Pancreas; Histopathology; Parsley; ultrastructure

Introduction: Silver nanomaterials; the engineered nanomaterials; have many industrial applications. They are used in manufacture of cosmetic and daily used products as food and clothes. Nanoparticles can pass through different biological body barriers, accumulate in the female reproductive organs as uterus and ovaries and exert their toxicity.Aim of the work: to evaluate the effect of silver nanoparticles on the histological structure of the endometrium using different histological and immunohistochemical techniques.Materials and methods: thirty-six adult female albino rats were divided into three equal groups; group I (control group), group II and group III. Silver nanoparticles were administered daily for 2 weeks at dose 30mg /kg and 300mg/kg respectively orally to group II and III. The size of the used nanoparticles is 20 nm. Specimens of uterus were taken to be processed for examination by light microscope (haematoxylin and eosin, Masson trichrome and TNF- alpha immunohistochemical staining) and transmission electron microscope.Results: AgNps-treated animals showed stratification, cytoplasmic vacuolation, discontinuation and desquamation in endometrial epithelial cells. The lamina propria showed cellular infiltration (inflammatory reaction), empty spaces and increase the deposition of collagen fibers (fibrosis). Ultrastructurally, they showed focal loss of the apical microvilli of the endometrial epithelial cells, apical cytoplasmic vacuoles, swollen, distorted and irregularly arranged mitochondria and large amount of secondary lysosomes and autophagic vacuoles. Focal separation of the epithelial cells with destruction of the intercellular junctions was seen. The lamina propria showed accumulation of collagen fibres and eosinophilic infiltration. Immunohistochemical study revealed highly significant increase in the TNF- alpha immunoexpression particularly in group III. All these changes were more severe in animals with high dose than those of low dose.Conclusion: silver nanoparticles induce structural changes in a dose dependent manner in the endometrium. So, it should be given cautiously to females to avoid uterine damage.

Covert mortality nodavirus (CMNV) is an alphanodavirus mainly infecting marine shrimp and co-inhabiting organisms in aquaculture ponds. To evaluate the possibility of CMNV prevalence in the wild fish species, epidemiological survey of CMNV infection in Larimichthys polyactis, the dominant species in the Yellow Sea and East China Sea, were conducted in the present study. We performed CMNV RT-LAMP assay in samples of L. polyactis collected in August 2018 and 2019 and found that CMNV prevalence was 18% and 7%, respectively. The nucleotide sequences of both RdRp and capsid protein genes of CMNV from L. polyactis were 99% similar to those of CMNV isolated from shrimp. CMNV-positive L. polyactis exhibited necrosis of cardiac muscle, oocytes loosely arranging, severe cytoplasmic vacuolation of hepatocytes, moderate pyknosis of brain pyramidal cells, degenerate renal tubular cells with ill-defined margins, and declined spleen cells in the histological examination. Moreover, CMNV-positive signals were further observed in pyramidal cells of the brain, the cortical area of the kidney, oocyte growth rings, and in necrotic tissues of cardiac muscle, liver, and spleen in the in situ hybridization assay. The results revealed that CMNV had colonized in the wild populations of L. polyactis and the ecological risk of CMNV spread and epidemic in wild fish in the coastal water was non-negligible.

Background: Repeated heating of vegetable oils especially palm oil that is commonly and commercially used in frying of food at homes and restaurants has been investigated for its risks on health status. It seemed to carry potential hazards on the liver tissue. Aim: To investigate the impact of eating foods fried with 5-times heated palm oil on liver of adult male rats for 8 weeks and the possibility of recovery of histomorphometric changes after stoppage of use of reheated palm oil for additional 4 weeks.Material and Methods: Thirty adult male albino rats were divided equally into 3 groups; control group (received normal balanced diet for 8 weeks), H5 group (received 5-times heated palm oil enriched diet for 8 weeks) and Recovery group (received five times heated palm oils for 8 weeks and then left on balanced diet for another 4 weeks). At the end of the experiment, animals were anesthetized with ether then sacrificed. Specimens taken from the liver were processed for histological evaluation. Morphometric studies were conducted and collected data undergone statistical analysis.Results: Histological examination showed alterations in liver tissue of H5 group including fat droplets, mononuclear cellular infiltration, dilatation of central vein and blood sinusoids, collagen deposition and degeneration and necrosis of hepatocytes. Ultrastructural examination showed lipid droplets, irregular mitochondria, cytoplasmic vacuolation, irregular nuclear envelop and dilatation of endoplasmic reticulum. Recovery group showed decreased lipid droplets, less dilatation and congestion of central vein and blood sinusoids, decreased inflammatory cells but few hepatocytes still show degeneration. Ultrastructure of hepatocytes of recovery group became more or less normal with restoration of cytoplasmic organelles. Morphometric results support the histological findings.Conclusion: Consumption of repeatedly heated palm oil is injurious to the liver tissue, and those injuries show possible recovery after stoppage of its consumption.

Introduction: Potassium bromate (KBrO3) is an oxidizing agent that is widely used as a flour improver. However, it induces genotoxic and carcinogenic effects on different body organs in a dose and duration-dependent manner. So, the aim of this study was: to explore the effects of KBrO3 on the structure of the rat jejunal mucosa and investigate the potential role of lycopene, a strong antioxidant molecule, in preventing or ameliorating the effect of KBrO3. Materials & Methods: Twenty-four adult male albino rats were used and divided equally into four experimental groups; control group, lycopene group that received 10mg of lycopene/kg/day/orally; KBrO3 group that received 100mg of KBrO3/kg/day/ orally and KBrO3 and lycopene group that received KBrO3 and lycopene in the same doses as in the previous groups. Animals were sacrificed after 4 weeks and the specimens from the jejunum were processed for histological, immunohistochemical, and ultrastructural examinations. Results: the jejunal mucosa of the KBrO3 treated group showed short and broad villi, discontinuity and desquamation of their lining epithelial cells, inflammatory cellular infiltration, and dilatation of the blood vessels. Moreover, there was a significant decrease in the number of goblet cells and PCNA immuno-stained nuclei in the jejunum. Ultramicroscopic examination showed swollen vacuolated mitochondria, dilated rough endoplasmic reticulum, and shrunken dark nuclei. Interestingly, the group treated with both lycopene and KBrO3 showed less cytoplasmic vacuolation and mitochondrial abnormalities in the epithelial cells lining the villi. Furthermore, there was a significant improvement in the height of jejunal villi, the number of goblet cells, and PCNA immuno-stained nuclei. In conclusion: KBrO3 induced cellular damage in the rat jejunal mucosa which was prevented by coadministration of lycopene.

This study evaluated the synergistic anti-cancer potential of cannabinoid combinations across the MDA-MB-231 and MCF-7 human breast cancer cell lines. Cannabinoids were combined and their synergistic interactions were evaluated using median effect analysis. The most promising cannabinoid combination (C6) consisted of tetrahydrocannabinol, cannabigerol (CBG), cannabinol (CBN), and cannabidiol (CBD), and displayed favorable dose reduction indices and limited cytotoxicity against the non-cancerous breast cell line, MCF-10A. C6 exerted its effects in the MCF-7 cell line by inducing cell cycle arrest in the G2 phase, followed by the induction of apoptosis. Morphological observations indicated the induction of cytoplasmic vacuolation, with further investigation suggesting that the vacuole membrane was derived from the endoplasmic reticulum. In addition, lipid accumulation, increased lysosome size, and significant increases in the endoplasmic reticulum chaperone protein glucose-regulated protein 78 (GRP78) expression were also observed. The selectivity and ability of cannabinoids to halt cancer cell proliferation via pathways resembling apoptosis, autophagy, and paraptosis shows promise for cannabinoid use in standardized breast cancer treatment.

Bhasmas are Ayurvedic herbo-mineral formulations that have been used since ancient times for therapeutic benefits. Godanti Bhasma (GB) is an anhydrous calcium sulfate preparation processed by heating of gypsum powder with herbal extracts. Thermo-transformation of gypsum into the anhydrous GB was confirmed by Raman and FT-IR spectroscopy. GB particle showed size range of 0.5-5 µm and neutral surface charge. Exposure to mammalian cells with GB particles showed massive vacuolation in their cytoplasm. Interestingly, no vacuolation was observed with parent gypsum particle. The result indicated that the cytoplasmic vacuolation by GB was due to its unique physicochemical property obtained during the thermo-transformation of gypsum. Using lysosomal inhibitors Bafilomycin A1 (BFA1) and Chloroquine (CQ), the process of vacuole formation was suppressed indicating GB induced vacuolation require acidic environment. The GB induced vacuolation was also found to follow dose and time dependent manner. Vacuolation often accompany with the sign of cell death whereas, in our study, massive vacuolation by GB did not induce any cell death. Moreover, GB treated cells survive with massive vacuolar process, which was reversed following post-treatment with vacuole inhibitors in GB treated cells, suggesting normal vacuolar function is essential for cell survival. Treatment of cells with GB was also found to induce translocation of LC3 protein from the nucleus to vacuolar membrane, indicating LC3 associated phagocytosis (LAP) is involved in the vacuolar process. Interestingly, the LAP function was found to be reversed in the cells treated with vacuole inhibitors. Our results provide a mechanistic correlation with GB induced vacuolation and associated LAP function, essential for cell survival.Abstract Figure

Background: Ulcerative colitis is a major health problem and its occurrence is progressively increasing around the world. Royal Jelly is widely used up in diets all over the world due to its beneficial effects: Antioxidant, antitumor and anti-inflammatory.Aim: This work aimed to investigate whether an oral pretreatment with Royal Jelly would have any effect on rats submitted to ulcerative colitis using different histological techniques.Material and Methods: Thirty adult male albino rats were divided into control, Royal Jelly (RJ) (received 100mg/kg/day royal jelly orally for two weeks), Dextran Sodium Sulfate (DSS) (received orally 5ml DSS 5% daily for seven days for induction of ulcerative colitis) and (DSS & RJ) (received royal jelly 7 days before induction of ulcerative colitis and continued during the induction period) groups. Colon speci-mens were processed for light and electron microscopic examinations. Quantitative assessment and statistical analysis were done for the mean number of goblet cells and the mean color intensity of cyclooxygenase 2 (COX 2).Results: Light microscopic examination of DSS group revealed desquamated epithelial cells, erosions, heavy mono-nuclear cellular infiltration, dilated congested vessels and abnormal shaped crypts. Statistical results revealed significant decreased goblet cell number and significant increased color intensity of COX-2 immune reaction in comparison to control group. Electron microscopic examination revealed shrunken cells, focal loss of microvilli, widening of intercellular spaces, cytoplasmic vacuolation, irregular nuclei and inflammatory cellular infiltration. DSS & RJ group revealed preserved mucosal architecture, statistically nonsignificant difference in mean goblet cell number but significant increase in color intensity of COX-2 immune reaction in comparison to control group.Conclusion: Royal jelly reduced histological alterations in induced ulcerative colitis.

Aim To assess various cytological changes for predicting radiosensitivity of oral squamous cell carcinoma by exfoliative cytology. Materials and methods Histologically proven 30 cases of oral squamous cell carcinoma who underwent fractionated radiotherapy in a dose of 45-60 Gy in 5 fractions/week were enrolled in the study. The exfoliative cytology smear was evaluated on lesional and adjacent oral mucosa before radiotherapy, during radiotherapy (8 and 11th fraction) and post radiotherapy (4, 6 and 8 weeks). Various parameters like multinucleation, cellular enlargement, nuclear enlargement, cytoplasmic vacuolation, cytoplasmic granulation, leukocytic infiltration were evaluated. Results Statistical significant values were seen in the inter-group comparison of all the parameters when compared adjacent mucosa and normal mucosa for leukocytic infiltration in pretreatment smear. Conclusion The study showed that radiation-induced cytological changes in oral squamous cell carcinoma have a significant dose-related increase. This dose-response relationship and the high intratumoral variations suggest that serial assay of these changes has potential use for radiosensitivity prediction. Clinical significance Radiosensitivity prediction can be evaluated by means of cytological smears in one stop crisis centre (OSCC) individuals subjected to fractionated radiotherapy by evaluating the cytological parameters.

The aim of this study was to investigate the effectiveness of alpha-lipoic acid (α-LA) against cyclosporine A (CsA)-induced pancreatic toxicity in rats. Thirty-two male albino rats were divided into four equal groups. Group I treated orally (per os, p.o.) with vehicles and served as control; Group II received α-LA (100 mg/kg b.w. /day, p.o.) for 21 days; Group III received CsA (25 mg/kg b.w./day, p.o.) for 21 days; and Group IV received α-LA 1 hr before oral treatment by CsA for 21 days. Histological examination of the pancreas of CsA-treated rats showed marked changes represented by wide interlobular septae that contained congested blood vessels, cytoplasmic vacuolation of some acinar cells, and distortion of the other cells. Most of the islets of Langerhans showed vacuolation, degenerative changes, and loss of uniform cellular distribution. Some of the islets appeared shrunken with few cells. In the CsA group, the immunohistochemical and morphometric study demonstrated a decrease in the number of insulin-secreting β-cells and also a reduction in islet diameters, with statistically significant difference (p0.001 and p = 0.004), respectively, compared with the control group. Ultrastructure of the exocrine and endocrine pancreatic cells of the CsA-treated group confirmed the light microscopic observation and showed dilated rough endoplasmic reticulum, decreased zymogen and secretory granules, damaged mitochondria, and abnormal nuclei. However, α-LA administration simultaneously with CsA resulted in some sort of regression of the previously mentioned effects.α-LA attenuated CsA-induced structural and ultrastructural changes in pancreatic cells, which were nearly reverted to their normal structure.

Several cationic-amphiphilic drugs such as chloroquine and amiodarone are known to induce phospholipidosis in the cornea by systemic administration. However, the characteristics of ophthalmological and pathological changes when phospholipidosis-inducing drugs are topically applied have not been well studied. This study was conducted to investigate the characteristics of corneal changes caused by topical application of chloroquine and amiodarone to Japanese white rabbits. The changes were evaluated by ophthalmological, histopathological, and ultrastructural examinations. An in vivo confocal microscopy was also applied to the chloroquine-treated corneas. In both chloroquine- and amiodarone-treated corneas, diffuse cloudiness was observed by slit-lamp biomicroscopy, and its transparency increased with duration of dosing. Confocal microscopy showed punctate dots in the corneal epithelium. Histopathologically, cytoplasmic vacuolation was found in the corneal epithelium and keratocytes in both chloroquine- and amiodarone-treated eyes. Furthermore, foamy cytoplasm of the corneal endothelium was observed in the chloroquine-treated eyes. Ultrastructural examination showed multi-lamellar inclusion bodies or membrane-like debris in the lysosome-like vacuoles in the cytoplasm of corneal cells, which is a characteristic of the lesions of phospholipidosis. These changes disappeared after a withdrawal period. Continuous dosing of chloroquine resulted in corneal erosion and focal corneal opacity as shown by gross observation and slit-lamp biomicroscopy. Confocal microscopy could detect the corneal changes prior to the appearance of these ophthalmological changes. The present study showed that phospholipidosis caused by ocular administration of chloroquine and amiodarone first induces reversible diffuse corneal cloudiness. Confocal microscopy is a useful method for monitoring induction of corneal phospholipidosis.

Introduction: Cyclophosphamide (CP) is a widely used anti-cancer drug which can induce serious male infertility.Aim of the study: The present study aims at determining the protective role of alpha-lipoic acid and royal jelly in improving biochemical, histological and ultrastructural disorders in the testis of rats induced by CP.Materials and Methods: 64 rats were separated into eight groups each of 8 rats. (G1) control group, (G2) alkaline solution treated group, (G3) DMSO treated group, (G4) Alpha-lipoic acid (LA) treated group, (G5) Royal jelly (RJ) treated group, (G6) CP treated group (5 mg/kg b.wt) three days per a week for 4 weeks, (G7) CP plus LA treated group (25 mg/kg b. wt) and (G8) CP plus RJ treated group (1g/kg b. wt). Animals were sacrificed after 4 weeks.Results: CP leads to an increase in lipid peroxidation in form of malonaldehyde (MDA) and decline in superoxide dismutase (SOD) in comparison with control. It caused histopathological changes in testes of rats including vacuolation, exfoliation of germ cells in the lumina of the seminiferous tubules, and maturation arrest. Furthermore, oedema was also observed and congestion of the intertubular blood vessels. Ultrastructurally, the boundary tissue of some tubules displayed noticeable changes; it was thickened and folded. Sertoli cells displayed an increase in the number of lysosomes and their nuclei showed signs of pyknosis, cytoplasmic vacuolation. Administration of LA and RJ to CP-treated rats revealed marked improvement in the altered level of SOD and MDA activities when compared with the CP-treated group and showed improvement in histopathology and ultrastructure of the testis.Conclusion: Treatment of the cyclophosphamide with the alpha-lipoic acid-induced great regaining of the damaged testicular tissues and royal jelly induced little regaining of the damaged testicular tissues, so LA was effective in treatment with CP than RJ with CP. This enhancement because of their antioxidant properties and its scavenging abilities against active free radicals.

Background: Levetiracetam is a broad-spectrum antiseizure agent and one of the most commonly prescribed drugs for epilepsy. The aim of this work was to assess the effect of levetiracetam at its therapeutic range on the liver and kidney of pregnant albino rats. Materials and methods: Forty pregnant rats were divided equally into two groups (I–II), Rats in the group I were gavaged 1.5 mL/day distilled water in two divided doses throughout pregnancy. Rats in the group II were gavaged 1.5 mL/day distilled water (containing 36 mg levetiracetam) in two divided doses throughout pregnancy. At the end of the experiment, blood samples were taken and the sera were separated and used for biochemical analysis. The kidneys and livers of both groups were excised and used for light and electron microscopic examination. Results: Treatment with levetiracetam induced undesirable histopathological changes in the liver and kidney of pregnant albino rats. These changes were in the form of distortion of the hepatic architecture, dilatation of the central and the portal veins, widening of the Bowman’s spaces, thickening and disruption of the glomerular basement membrane, fusion and effacement of secondary foot processes, cytoplasmic vacuolation, and swollen mitochondria with loss of their cristae. Such changes were confirmed by alteration of certain biochemical parameters related to the liver and kidney functions. Conclusions: Levetiracetam induced deleterious effects on the liver and kidney of pregnant albino rats. Further investigations are recommended to clarify the mechanism of levetiracetam toxicity.

Non-apoptotic cell-death induction is a potential strategy for cancer treatment. Cytoplasmic vacuolation-associated cell death represents a novel type of non-apoptotic cell-death. Here, we showed that isobavachalcone (IBC), a naturally occurring chalcone compound, selectively induced cell death with massive cytoplasmic vacuolation in some leukemic cells but not in normal peripheral blood cells. Although the IBC-induced cell death displayed certain apoptotic changes, the caspase inhibitor Z-VAD-FMK did not significantly suppress IBC-induced cell death. IBC-induced vacuoles are acidic in nature, as revealed by neutral red staining. However, these vacuoles could not be labeled by lysosome or mitochondrial trackers. Moreover, the knockdown of several autophagy-related genes, such as LC3, Beclin-1, and ATG7, did not inhibit IBC-induced vacuolation. Transmission electron microscope examination revealed that these vacuoles mainly derived from the endosome. Surprisingly, Vacuolar-type H + -ATPase inhibitors, weak bases, such as chloroquine and AKT inhibitors, markedly abrogated vacuolization but enhance IBC-induced cell death, suggesting that IBC-induced vacuolation and cell death go into different direction and the vacuolization is a protective action rather than a part of the death mechanism. In conclusion, by using IBC as a chemical probe, we provide new characteristics of methuosis-like cell death. Inducing methuosis-like cell death may represent a novel strategy to combat leukemia.

Obesity is a multi-factorial chronic disorder which causes some serious problems. Sibutramine is anti-obesity drug with established efficacy in sustained weight reduction, but it has a side effect on blood pressure and heart rate elevation. The present study aimd to pinpointing the effects of sibutramine and green coffee in ameliorating the histological and ultrastructural disorders in the testes of rats induced by obesity. This study was assessed in male albino rats (120-150 g). The rats were divided into four groups: the 1st group received a normal diet and acted as a control negative, the 2nd high fat diet (HFD) group acted as control positive, the 3rd HFD group treated with sibutramine (10 mg/kg body weight/day), and the 4th HFD group treated with green coffee (100 mg/kg body weight/day). The present histological study revealed that sibutramine caused histopathological changes in the testes of obese rat including vacuolation, maturation arrest and exfoliation of germ cells in the lumina of the seminiferous tubules. Moreover, congestion of the intertubular blood vessels and proliferation of Leydig cells in the interstitial tissue were also observed. Ultrastructurally, the boundary tissue of some tubules showed marked changes; it was folded and thickened. Sertoli cells showed cytoplasmic vacuolation, vacuolated mitochondria, increased number of lysosomes and their nuclei showed signs of pyknosis. Moreover, Leydig cells revealed vacuolation and decrease in the number of lipid droplets. On the other hand, treatment of the obese rats with green coffee induced great recovery of the damaged testicular tissues. This improvement may be due to the antioxidant properties and scavenging abilities of green coffee against active free radicals.

The Rhipicephalus sanguineus is considered a species of medical and veterinary importance. The feeding process of these animals occurs due to the combined action of their mouthparts and the saliva produced by the salivary glands, vital organs for the biological success of the ticks. In addition, these glands act as storage sites for the pathogens transmitted to the host through the inoculation of the saliva. In this sense, the present study had the objective to analyze the behavior of male Wistar rat hepatic cells submitted to in vivo application of the salivary gland extract (SGE) obtained from R. sanguineus female ticks. The study involved five groups (four male adults each): CG (non-inoculated individuals); PBS1 (one phosphate buffer saline injection); PBS2 (two PBS injections); SGE1 (one injection of SGE at 0.04 μg/μL) and SGE2 (two injections of SGE at 0.04 μg/μL). After the exposures, the livers were removed and submitted to the following histological and histochemical stains: HE, toluidine blue, Xylidine Ponceau, alcian blue/PAS, and osmium-imidazole. The results showed that both the PBS and the SGE caused hepatic moderate alterations, such as: (a) emergence of lipid plaques among the hepatic cords; (b) cytoplasmic vacuolation of the hepatic cells; (c) hepatocytes showing pyknotic nuclei; (d) presence of homogeneous or granular secretion in the cytoplasm of the hepatocytes. Despite the slight morphological alterations observed in the hepatic cells and tissue, the latter did not show signs of disorganization after the exposure to the extracts.

Purpose: To evaluate the effect of lignocaine on growth and apoptosis indication of primary human Tenon’s capsule fibroblast (HTFs) in an in vitro model. Patients and Methods: Tenon’s capsule tissue obtained from patients undergoing trabeculectomy were grown in cell culture medium. The effect of different concentrations of lignocaine (0.5, 1.0, 1.5, and 2%) on the morphology and growth of the fibroblasts was studied using microscopy, cell viability, and proliferation assay, and apoptosis was detected using the FITC Annexin V Apoptosis Kit. Results: Morphological changes similar to those of apoptotic cells, including cytoplasmic vacuolation, shrinkage, and rounding were visualized in the cells treated with concentrations greater than 1.0% (i.e., 1.5, 2.0%). Though proliferation inhibition was found with all four concentrations (0.5–2.0%), the viability of cells decreased from 1.0% lignocaine. Conclusion: 0.5% lignocaine prevents proliferation of fibroblasts without causing apoptosis in vitro.

Fungal toxins in nutrition can cause organ dysfunction or even failure. Aflatoxin B1 (AFB1)-induced renal impairment is not sufficiently studied regarding its extent and prevention. The aim of this experiment was to study the effect of AFB1 on renal cortical tissue and whether its possible harmful effect could be prevented by the conventional economical antioxidant, vitamin E. Forty rats were divided into four groups; I-IV. Group I represented the control while the others received vitamin E (Vit E), AFB1 and AFB1+Vit E, respectively. Renal cortex specimens were taken from each group after 25 days. Then, specimens were prepared for histological study by hematoxlyin and eosin (H&E), Masson's trichrome, caspase-3 as well as for ultrastructural examination and oxidative stress parameters evaluation. Data were morphometrically and statistically analyzed. In AFB1-treated group, focal tubulo-interstitial affection in the form of tubular cytoplasmic vacuolation, mitochondrial disruption, numerous lysosomes, marked increase in collagen deposition and in caspase-3 expression were observed. Glomerular impairment in the form of fusion of podocytes enlarged foot processes and thickening of the glomerular basement membrane (GBM) with loss of its trilaminar appearance were detected. In the group treated by AFB1+Vit E, there were minimal affection of the histological structure of the renal cortex as well as significant increase in the anti-oxidative parameters which were significantly decreased in the AFB1-treated group. Therefore, Vit E could be considered in wide experimental studies to be a first choice antioxidant of high cost-effectiveness in prevention of fungal toxins pro-oxidant-induced renal impairment.

In 2012, a freshwater farm in south China experienced a severe disease outbreak in cultured giant mottled eel Anguilla marmorata, resulting in high mortality. The diseased eels showed extreme ulcerative injuries throughout their bodies and obvious swelling of the liver and body kidney. A pure culture of a bacterial strain, designated HZHM, was isolated and identified as Edwardsiella tarda based on its physiological and biochemical characteristics and on phylogenetic analysis of 16S rRNA and fimbrial genes. The HZHM strain was unable to produce hydrogen sulphide (H2S) from thiosulphate in biochemical testing. In addition, results of the challenge trial confirmed that the HZHM strain was virulent for A. marmorata, with an LD50 value of 1.3 × 106 colony-forming units (CFU). Histologically, severe hemorrhage occurred in most organs, increased melano-macrophage reaction was observed in the spleen and body kidney, and cytoplasmic vacuolation and liquefactive necrosis were found in the brain. To our knowledge, this is the first report of E. tarda-associated pathogenicity in A. marmorata.

Cytological responses in different organs of sentinel organisms have proven to be useful tools for characterizing the health status of those organisms and assessing the impact of environmental contaminants. Our study shows that nickel (II) accumulated in both germ cells (oogonia and developing oocytes) and somatic cells (muscle cells, follicle cells) in the Astacus leptodactylus ovary. Muscle cells from ovarian wall show disorganization and the disruption of cytoplasmic microtubules and pyknosis of the cell nucleus. Follicle cells, both those that surround the developing oocytes and also those that are not associated with the oocytes contained within the cytoplasm vacuoles of different sizes, degenerated mitochondria, myelin bodies, disorganized microtubules, and pyknotic nuclei. The most evident pathological phenomenon was the alteration and disorganization of the basal matrix, which separates the ovarian interstitium from ovarian follicles compartment. Exposure to nickel induces cytoplasmic vacuolation in oogonia and developing oocytes, structural alteration of the developing yolk granules and condensation of the nucleoli. Ultrastructural autometallography has shown grains of silver-enhanced nickel inside the cytoplasm of the muscle cells with altered morphology, including the cytoplasm, nucleus, and basal matrix of the follicle cells, and in intracisternal granules and developing yolk granules of the oocytes.

Nonalcoholic fatty liver disease is a major health problem and is considered the most common worldwide liver disease. Pomegranate has many biological activities and could modify the risk of hypercholesterolemia. The objective of the current research was to study the histological changes of experimentally induced fatty liver and possible protection by pomegranate. For this purpose, 50 adult male albino rats were divided into four groups, control group, pomegranate treated group that were given pomegranate juice for six weeks, fatty liver induced group that were fed on high fat diet for six weeks and protective group that were fed on high fat diet and received pomegranate juice for six weeks. Histological changes were detected in the fatty liver induced group in the form of disturbed hepatic architecture, dilatation and congestion of central veins, blood sinusoids and portal veins. Most of hepatocytes showed variable degrees of cytoplasmic vacuolation, mitochondrial structural changes, dilatation of endoplasmic reticulum in addition to nuclear structural changes like condensed chromatin, irregular shrunken nuclei and vacuolated nuclei. All these changes were associated with inflammatory cellular infiltrations, deposition of collagen fibers around the central vein, blood sinusoids, portal areas and in between the hepatocytes in addition to significant increase in number of hepatic stellate cells that was proved by electron microscope and confirmed by immunohistochemical study. Moreover, these structural changes were much less pronounced in animals treated with pomegranate either with or before receiving high fat diet. These findings suggested that pomegranate has a protective effect against experimentally induced fatty liver.

Rotavirus diarrhea is a major worldwide cause of infantile gastroenteritis; however, the mechanism responsible for intestinal fluid loss remains unclear. Water transfer across the intestinal epithelial membrane seems to occur because of aquaporins (AQPs). Accumulating evidence indicates that alterations in AQPs may play an important role in pathogenesis. Here, we focus on changes in AQPs in a mouse model of rotavirus diarrhea. In the present study, 32 of 35 mice developed diarrhea and mild dehydration within 24 hours after infection with rotavirus strain SA11. Intestinal epithelial cells demonstrated cytoplasmic vacuolation, malaligned villi, and atrophy. AQP1 expression was significantly attenuated in the ileum and colon in comparison with controls; likewise, AQP4 and -8 protein expression were significantly decreased in the colon of rotavirus diarrhea-infected mice. In contrast, AQP3 protein expression was significantly increased in the colon of rotavirus-infected mice in comparison with controls. These results indicate that rotavirus diarrhea is associated with the downregulation of AQP1, -4, and -8 expression. Therefore, AQPs play an important role in rotavirus diarrhea.

The present study examined the apoptosis inducing effects of Amaranthus spinosus L. aqueous extract in Allium cepa root meristematic cells and human erythrocytes. Cytogenetic assay revealed many apoptosis inducing cytogenetic aberrations viz., cytoplasmic breakage, cytoplasmic disintegration, cytoplasmic shrinkage, receding of cytoplasm, cytoplasmic vacuolation, enucleated cell, ghost cell, nuclear vacuolation, nuclear fragmentation and nuclear disintegration. A remarkable modification of red blood cell surface morphology was observed in the result of RBC assay. The treated RBCs show membrane blebbing and shrinkage, features typical for apoptosis in nucleated cells. Significant induction of cell death was observed in treated Allium root tip cells after Evans blue staining, disclosing the membrane damage potential of the plant extract. TTC assay results in reduced mitochondrial/metabolic activity in Allium root tip cells after treatment, designating the adverse effect of plant extract on mitochondrial respiratory chain. These results confirm the apoptosis inducing potential of A. spinosus extract. Confirming the present results by further in vitro studies, it can be effectively targeted against cell proliferation during cancer treatment by inducing apoptosis. Thus from the present investigation it can be concluded that the aqueous extract of A. spinosus exhibited apoptosis induction and cytotoxic activities.

Alloxan has been widely used to produce experimental diabetes mellitus syndrome. This study was undertaken to investigate the protective effect against alloxan-induced pancreatic damage by curcumin. Rats were divided into four groups. (1) Control group. (2) Curcumin control group. (3) Diabetic group with a single intraperitoneal injection of 100 mg alloxan/kg b.wt. (4) Diabetic group treated with curcumin orally at a dose of 60 mg/kg b.wt dissolved in distilled water. Blood samples were collected for the detection of serum glucose levels. The pancreas was prepared for histopathological, immunohistochemical stain using anti-insulin antibody and ultrastructural studies. The electron microscopic examination of diabetic pancreas showed marked changes in pancreatic acini represented by dilated rough endoplasmic reticulum, decrease of secretory granules, cytoplasmic vacuolation and irregular contours of nuclei. β-Cells showed fusion of some granules, obvious vacuolation and pyknotic nuclei. α Cells revealed focal necrosis and vacuolation, dilated rough endoplasmic reticulum and depletion of secretory granules. Curcumin improved the histopathology and ultrastructure changes of the islets, alpha cells and exocrine acini, which nearly reverted to their normal structure. It increased insulin immunoreactivity and decreased the elevated glucose concentrations.

Conjugation of therapeutic proteins with high molecular weight polyethylene glycols (HMW PEGs) is used to extend the half-life of biologics. To evaluate the effects of HMW PEGs in animals, we used an immunohistochemical procedure to study the tissue distribution and toxicity of unconjugated HMW PEGs in rats given 100 mg/kg 10KPEG, 20KPEG, or 40KPEG intravenously. Both the PEG cellular distribution and the histology were different between groups. In 10KPEG and 20KPEG groups, PEG immunoreactivity was most prominent in the renal tubule epithelium and in alveolar macrophages and hepatic Kupffer cells and cellular vacuolation was absent. In contrast, rats given 40KPEG had strong PEG immunoreactivity in splenic subcapsular red pulp macrophages, renal interstitial macrophages, and choroid plexus epithelial cells that was frequently associated with cytoplasmic vacuolation. While the vacuolation appeared to be an adaptive response, there was focal renal tubular epithelial degeneration associated with strong PEG immunoreactivity in one rat given 40KPEG. These data indicate that both the tissue distribution and the vacuolation observed with unconjugated HMW PEGs are markedly influenced by the molecular weight of the PEG and that when vacuolation is observed it is likely an adaptive change that is associated with PEG cytoplasmic immunoreactivity.

The nasal septa of fetal rabbits at 26 days of gestation were harvested by cesarean section of the does while under anesthesia and then exposed to Bordetella bronchiseptica or its lipopolysaccharide (LPS) for periods of 2 and 4 hours. A total of 240 explants were used. The tissues were examined using the Hematoxylin & Eosin technique. Then, semithin sections (0.5 m) were stained with toluidine blue and examined with indirect immunoperoxidase (IPI) and lectin histochemistry. The most frequent and statistically significant findings were as follows: (1) cell death and increased goblet cell activity when exposed to bacteria and (2) cell death, cytoplasmic vacuolation and infiltration of polymorphonuclear leukocytes when exposed to LPS. The lesions induced by the bacterium were more severe than with LPS alone, except for the cytoplasmic vacuolation in epithelial cells. IPI stained the ciliated border of the epithelium with the bacterium more intensely, while LPS lectin histochemistry preferentially labeled the cytoplasm of goblet cell. These data indicate that B. bronchiseptica and its LPS may have an affinity for specific glycoproteins that would act as adhesion receptors in both locations.

Determining the time of death is a constant dilemma in forensic medicine. While age-old conventional methods are adequate for estimation of time of death during routine medico legal autopsies, newer methods are being investigated. The present study aims to evaluate light-microscopically observable ‘degenerations’ of labial mucosa at varying post-mortem intervals. Labial mucosa samples obtained from 31 non-refrigerated cadavers at varied post-mortem intervals (0–8 hrs, 8–16 hrs and 16–24 hrs) were evaluated for histologic post-mortem changes in the epithelium and connective tissue. The early changes in the epithelium included homogenization, eosinophilia, nuclear changes while cytoplasmic vacuolation, shredding, ballooning, acanthosis, epithelial degeneration and split were observed in the later post-mortem intervals (16–24 hrs). Reduction of the submucosal compartment was the earliest manifestation observed in the connective tissue along with disruption of collagen, adipose tissue and muscle. Increased sp...

Effects of glyphosate-based commercial herbicide, Excel Mera 71 were performed to evaluate the pathological responses in stomach and intestine of Heteropneustes fossilis (Bloch) for duration of 30 days both under rice field and laboratory concentrations. Under light microscopy, stomach showed distortion in columnar epithelial cells (CEC), lamina propria (LP) and gastric glands under both conditions, but the severity of responses were more pronounced under laboratory condition. Severe fragmentation in mucosal folds (MF) and epithelial cells, and excessive mucus secretion were observed under scanning electron microscopic (SEM) study in laboratory study but alterations in stratified epithelial cells and microridges structure were not prominent under field; while deformation in mitochondria and endoplasmic reticulum and cytoplasmic vacuolations were seen under transmission electron microscopic (TEM) observation in both the conditions, but less severe in field study. Intestine showed distortion and fatty deposition in lamina propria, lifting of CEC and loss of brush border structures in laboratory study, while damage only at the tip of the mucosal villi and CEC were observed under field study through light microscopic observation. Under SEM study, degeneration in CEC and excessive mucus secretion over CEC were prominent, while under TEM study deformation and necrosis in mitochondria, severe cytoplasmic vacuolation, necrosis, cytosolic disorganization, and loss of cellular compartmentation were observed in laboratory study, but intestinal epithelium showed normal appearance under field observation. Therefore, present investigation depicted that long-term glyphosate exposure caused stronger pathological alterations under laboratory condition compared with field study and finally, displayed responses could be considered as indicators of herbicidal contamination in aquatic environment.

Objective: Present study was aimed to study the cytopathological effects of almix herbicide in Indian freshwater teleost, Oreochromis niloticus (Linn.) both under field and laboratory exposure. Methods: O. niloticus (Linn.) was exposed to almix herbicide at sublethal concentrations of 8 g/acre and 66.67 mg/L under field and laboratory conditions respectively for 30 days. Field experiment was performed in cage, submerged in the field pond. Cytopathological study both through light and electron microscopic (scanning electron microscopy and transmission electron microscopy) observations were based on gill, liver and kidney. Results: Histopathological observations revealed hypertrophy and proliferation in gill epithelium, curling and fusion of secondary gill lamellae (SGL), distortion in chloride and pillar cells under laboratory experiment. Scanning electron microscopy displayed severe loss of normal array of concentric microridges, swelling of microridges, damage in epithelial cells and appearance of vacuoles on the stratified epithelium, while loss of regular pattern of microridges were observed under field condition. Transmission electron microscopic study of gill showed severe damages which included degenerative changes in mitochondria, cellular vacuolation, damage in tubule vascular system, presence of lipid droplets, elongated nucleus, but in case of field experiment dilated mitochondria and cytoplasmic vacuolation were more prominent. Degenerative hepatopancreas, necrosis in hepatocytes, severe cytoplasmic vacuolation and disarrangement of hepatic cords in liver of O. niloticus were prominent seen under light microscopy in the laboratory condition, but in field condition elongated hepatocytes with increased nuclei and vacuolation in cytoplasm of hepatocytes were prominent, while TEM study showed degeneration in mitochondria, dilation in rough endoplasmic reticulum, damage in nucleus and appearance of cytoplasmic vacuolation in hepatocytes under laboratory condition. In kidney, degenerative changes in PCT and DCT, shrinkage of glomerulus, vacuolation in the haematopoietic tissues and excess fat deposition were notable changes. In TEM study necrosis in nucleus, severe vacuolation, appearance of endoplasmic reticulum as whorl pattern, degeneration in mitochondria in kidney were serious after almix exposure. Conclusion: Present study claimed the more profound responses under laboratory condition compared to field and different significant marked changes in these two conditions were prominent. Therefore, these responses in gill, liver and kidney of O. niloticus could be considered as potential of exposure of agrochemicals.

The present investigation was designed to evaluate the effect of two oral administered antibiotics (Rifampicin and Tetracycline) on some physiological parameters in the serum of male albino rats. Histopathological alterations in liver and kidney were also examined. Data showed that treatment of rats with rifampicin caused a significant increase in the total cholesterol, triglycerides and LDL-cholesterol levels, while HDL-cholesterol level showed a significant decrease. Moreover, significant increases in serum AST, ALT, bilirubin and urea were observed. Also, the levels of the total protein, albumin and alpha 1-globulin were significantly decreased. No significant changes were recorded in the rest of the globulin fractions (alpha 2-, beta- and gamma-globulin) and albumin/globulin ratio (A/G) as well as creatinine level. In the serum of tetracycline-treated rats, the triglycerides, LDL-cholesterol, AST, ALT, bilirubin, urea, creatinine and gamma-globulin levels increased significantly. On the other hand, HDL-cholesterol, total protein, albumin levels and A/G ratio showed significant decreases. No significant changes in the total cholesterol, alpha 2- and beta-globulin levels were detected. Histological examination of the liver and kidney in the rifampicin-treated rats indicated that the liver pathology includes necrosis of hepatocytes, cytoplasmic vacuolation, and distended sinusoids with some lymphatic aggregations. In the kidney, the glomeruli increased in size, the mesangial matrix was expanded and the renal tubules were degenerated. Histological analysis of liver samples of tetracycline – treated rats revealed high vacuolation of the cytoplasm of hepatic cells, sinusoidal dilation, hepatocellular necrosis and disappearance of the cell membrane in some hepatocytes. The kidney sections of rats treated with tetracycline showed shrinkage of the glomeruli, widening of the Bowman’s space, in addition to necrosis and vacuolation of the renal tubules.

Chordoid meningioma is an uncommon variant of meningioma, and is very rarely found in the pineal region. We report a case of pineal region chordoid meningioma occurring in a young woman complicated by repetitive hemorrhages in the setting of pregnancy. A 23-year-old woman, 28 weeks pregnant, was transferred to our hospital for further management of a multi-septated, hemorrhagic pineal region mass and hydrocephalus. MRI revealed a heterogeneous T2-hyperintense lesion measuring 1.7 × 1.7 cm in the pineal gland. Resection of the tumor through an occipital transtentorial approach was performed. Histopathologic examination of the lesion confirmed the diagnosis of chordoid meningioma demonstrating cords and clusters of eosinophilic cells with rare cytoplasmic vacuolation arranged in a mucinous stroma. Additionally, there was abundant lymphoplasmacytic infiltration within the tumor. The details of this case are presented with a review of the literature.

Histopathological alterations in gill, liver and kidney of common carp, Cyprinus carpio, intoxicated with sub-lethal concentrations of chlorpyrifos (O,O,-diethyl-O-3,5,6-trichloro-2-pyridyl phosphorothioate) pesticide (1 and 100 μg/L) for a period of 14 days were analyzed under light microscope. Gill exhibited hyperplasia and hypertrophy of gill epithelium, blood congestion, dilation of marginal channel, epithelial lifting, lamellar fusion, lamellar disorganization, lamellar aneurysm, rupture of the lamellar epithelium, rupture of pillar cells and necrosis. Alterations in hepatocytes were more pronounced, including nuclear and cellular hypertrophy, cellular atrophy, irregular contour of cells and nucleus, cytoplasmic vacuolation, cytoplasmic and nuclear degeneration, cellular rupture, pyknotic nucleus, necrosis and melanomacrophages aggregations. Histopathological lesions in kidney were cellular and nuclear hypertrophy, narrowing of tubular lumen, cytoplasmic vacuolation, hyaline droplet degeneration, nuclear degeneration, occlusion of tubular lumen, tubular regeneration, dilation of glomerular capillaries, degeneration of glomerulus and hemorrhage in Bowman's space. The most significant conclusion drawn from this study was that with the increased concentration and duration the toxicosis of chlorpyrifos would be enhanced as shown through the analysis of mean assessment value (MAV) and degree of tissue changes (DTC) also.

The study was carried out on a total of 100 broiler chicks divided into six equal groups at day 7 of age. Birds were fed copper sulphate and urea in different combinations for up to 37 days and then the birds of all the groups were fed plan feed for one week. The general signs were an increased water intake, ruffled feathering, watery droppings along with salivation in treatment groups. These signs were mild in groups fed low level of urea, while were severe in fed higher levels of these compounds together. Mild to moderate gross changes were observed in the birds of group B, C and D, while more pronounced changes were seen in birds of group E and F. In the latter groups, the liver was pale to yellowish and fragile. Kidneys were enlarged, swollen, congested and sometimes hemorrhagic. Histologically, mild cytoplasmic vacuolation and condensation/pyknosis or disappearance of the nucleus in the cells of the liver and kidney were the salient changes observed in the treatment groups, those were severe in birds fed higher levels of the two compounds. Changes in lungs were congestion and edema. Changes in the bursa of Fabricius were mild cytoplasmic vacuolation, cell depletion and chromatolysis. The live and carcass weights were lower in broilers fed higher levels of both copper and urea than the control group. The weights of kidney and heart were higher in birds fed higher levels of both of the compounds than the control group. It can be concluded from the present study that urea above 2% and copper sulphate above 1 gm in combination cause tissue damage, especially the liver and kidneys.

In the present study, goldfish toxicity and superficial damage from 1-methyl-3-octylimidazolium bromide ([C8mim]Br) exposure were evaluated by an acute toxicity test. These results show that the 24-h 50% lethal concentration for [C8mim]Br in goldfish is 244 mg L−1, and this indicates that [C8mim]Br is a chemical with moderate or low toxicity to organisms. Scanning electronic microscope and histological observations revealed that acute exposure to [C8mim]Br induced obvious superficial damage to the skin, gill filaments, and intestinal villi of the goldfish, and this suggests that the skin, gills, and intestines may be the first direct targets of the ionic liquid in this fish. Histological examination also indicated that [C8mim]Br-exposure caused damage to the goldfish's hepatopancreas and kidney, consisting mainly of hepatic cords in a loose connection, hepatic cytoplasmic vacuolation, renal parenchyma vacuolization, and intumescence of the renal tubule. In addition, we found that [C8mim]Br caused a significant increase in malondialdehyde (MDA) level in the hepatopancreases from these goldfish, and thus we suggest that the MDA level may be a biomarker of [C8mim]Br-toxicity in goldfish. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Intoxication with Ipomoea carnea has been reported in goats, sheep, and cattle in tropical regions worldwide. The disease has been characterized only in goats; therefore, the present study was conducted in sheep. Nine animals were fed feed rations that contained 3 different concentrations of Ipomoea carnea subsp. fistulosa. Individual intake varied between 10.5 and 135.2 g of fresh plant per kilogram of body weight (BW) per day. Animals first showed clinical signs between day 43 and day 63. The maximum survival time was 133 days. Sheep presented with weight loss and neurologic abnormalities. Neurologic signs were dominated by marked depression, abnormal behavior, and musculoskeletal weakness, with poorly defined motor and proprioceptive deficits. In mature animals, cytoplasmic vacuolation, consistent with accumulation of secondary lysosomes, affected neurons, astrocytes, exocrine pancreatic acinar epithelia, hepatocytes and Kupffer cells, renal tubular epithelia, thyroid follicular epithelia, cortical adrenal epithelia, endothelia and perivascular cells, and macrophages in lymph nodes and spleen. In the central nervous system, there was axonal degeneration and astrogliosis. Abortion was observed as early as day 22 of the trial. In fetal tissues and placenta of chronically poisoned ewes, cytoplasmic vacuolation was histologically detected in neurons, exocrine pancreatic acinar epithelia, hepatocytes, renal tubular epithelia, and thyroid follicular epithelia. All the sheep developed a glycoprotein storage disease, with lysosomal accumulation of N-glycosidically linked oligosaccharides, which was indistinguishable from that induced by the alkaloid swainsonine alone.

Rabah, S.O., Ali, S.S., Alsaggaf, S.M. and Ayuob, N.N. 2010. Acute taxol toxicity: the effects on bone marrow mitotic index and the histology of mice hepatocytes. J. Appl. Anim. Res., 38: 201–207. Hepatotoxic effects of acute intraperitoneal administration of 3 doses; MTD (Maximum tolerated dose) 1.7, ID (Intermediate dose) 1.15 and MD (Medical dose) 0.6 mg/kg Taxol were histologically studied. Mitotic index in hone marrow cells was used to test the drug effect on cell cycle. Vascular congestion, dilation and bile ducts dilatation was observed in liver. Hepatocytes became ballooned and the cytoplasm appeared vacuolated. Apoptotic cells were frequently encountered in all samples. Ultrastructure changes included degeneration of hepatocytes cellular organelles such as endoplasmic reticulum and mitochondria, lipid accumulation and cytoplasmic vacuolation. A significant decrease in mitotic index values in bone marrow cells was observed with higher doses after 24, 48 h. The frequencies of MicroNucleate...

Cytoplasmic vacuolation of sensory neurons has been reported to occur within the dorsal root ganglia in studies investigating various neuropathic conditions including the effects of neurotoxic chemicals. In this study, we investigated this lesion in adult (98–119 days old) male Long-Evans rats, after multiple exposures to two organophosphates (tri-ortho-tolyl phosphate [TOTP] and chlorpyrifos) and the modifying effects of concurrent corticosterone. Tri-ortho-tolyl phosphate was administered by gavage (75, 150, or 300 mg/kg) every other day between days 14 and 28 and between days 49 and 63, chlorpyrifos (60 mg/kg) was administered subcutaneously on days 7 and 42, and corticosterone was provided in the drinking water throughout the study at a concentration of 400 µg/mL. Although relatively uncommon, there was an increase in frequency of cytoplasmic vacuoles seen in treatment groups having multiple exposures to TOTP. They were characterized as peripherally located, single-limiting membrane-bound structures in the neuronal perikarya. There was no associated cell death, even when vacuoles were large. This is the initial report of an association of this change following exposure to neurotoxic organophosphates.

In April 2007, two newborn springboks (Antidorcas marsupialis) from a zoo of southern France were found dead. Necropsy was performed on the two animals and revealed arthrogryposis, mild facial structural abnormalities, and bilateral enlargement of the kidneys with concurrent hydronephrosis in both newborns. Histopathologically, extensive cytoplasmic vacuolation of neurons in the central nervous system, thyroid follicular epithelium, renal tubular epithelium, enterocytes, hepatocytes, and ruminal epithelial cells was the most remarkable lesion in both animals. By electron microscopy, the vacuoles were membrane bound and contained scattered membranous and granular material within a primarily electron-lucent background. Hence, a diagnosis of lysosomal storage disease was established, with gross, histological, and ultrastructural features suggestive of an inherited form of mannosidosis. This report documents the first case of lysosomal storage disease in springboks.

Objectives: Recent reports have shown significant associations between organopshophorus pesticide (OP) exposure and decreased sperm motility in workers and laboratory animals. However, the notion that OPs possess spermatotoxicity has yet to be established. The aim of this study was to clarify the effects of OP exposure on detailed sperm toxicity markers, i.e., motility, morphology and sperm adenine nucleotide contents, and the histopathology of the testis and epididymis. Methods: Ten-week-old Wistar rats were divided into 4 groups (n=10) and orally administered corn oil, dichlorvos (DDVP; 5, 10 mg/kg) or diazinon (DZN; 3 mg/kg) 6 days a week for 9 wk. Sperm motility and morphology markers were analyzed with a computer-assisted sperm analysis (CASA) system. Results: In addition to a significant decrease in acetylcholinesterase (AChE) activities and a significant increase in urinary OP metabolites, DDVP and DZN significantly reduced sperm motility, but they did not influence sperm adenine nucleotide contents. The OPs also significantly increased the percentage of broken sperm, and DDVP significantly increased the percentage of cytoplasmic droplets. Importantly, both OPs significantly increased cytoplasmic vacuolation and nuclear shrinkage in the epithelial cells of the ductus epididymis, whereas the testes did not show significant histopathological changes. Conclusions: The broken sperm and cytoplasmic droplets as well as reduced sperm motility were the relevant spermatotoxicity makers of DDVP and DZN. To our knowledge, this is the first report to suggest that the above-mentioned OP-induced spermatotoxicity is related to histopathological impairment of the caput epididymis.

Fumonisin B(1) (FB(1)), the most prevalent member of toxins produced by several species of Fusarium molds, which occur mainly in maize, causes several fatal hepatopathies and nephropathies of animals. The current study was scrutinized to ascertain different cytotoxic and morphological transformations in rat hepatocytes induced by the treatments of diverse concentrations (300, 500, or 1000 microM) of fumonisin B(1) in vitro, using both monolayer and spheroid cultures. In each hepatocyte culture, the cytotoxicity of FB(1) was augmented in dose- and time-response manners. Morphological transformations among FB(1)-treated groups integrated accumulation of lipid droplets, cytoplasmic vacuolation in hepatocyte monolayers, and bleb formation in the hepatocyte spheroids. Additionally, electron microscopy revealed the loss of microvilli, mitochondrial swelling, and formation of lamellar membranous whorl in the vacuoles and bile canaliculi-like structures. Appearance of electron dense bodies in the monolayers, and loss of cell-to-cell contact in spheroids were depicted in 1000 microM FB(1)-treated hepatocytes. These outcomes insinuate different vital events in explaining morphological transformations in the cell membrane and organelles, induced by fumonisins in rat hepatocytes.

The present study investigated the sorbitol toxicity on the retinas of normal albino rats and founded by the light microscope that intra-peritoneal injection of Sorbitol (10-mg/kg-body weight per day) for 24 weeks produced similar diabetic like retinal lesions in these rats. The retinopathic effects of sorbitol injection affect retinal microvessels, pigment epithelium, neural retina and glial cells. Cytoplasmic vacuolation of the pigment epithelium and oedema of the neural retinal cells were evident. Microvascular abnormalities include thick-walled, elongated and dilated blood capillaries. The abnormal capillaries showed aneurysms and were occluded with deformed, fragmented, and adherent blood cells. Another finding was the pyknosis of glial cells. The present investigation concluded that sorbitol is toxic to the retinal tissue and it may play a role in the setup of diabetic retinopathy.

Objective To investigate the effects of herbs for replenishing yin to tonify kidney on testicular ultrastructural changes in rats with glucocorticoid-induced kidney deficiency. Methods Thirty rats were randomized into three groups: normal control group, untreated group and Erdi Biejia Decoction (EDBJD)-treated group. Kidney deficiency rat model was induced by glucocorticoid. Testicular structure and ultrastructure were observed under the light microscope and the transmission electron microscope. Results The light microscope revealed the decreased thickness of seminiferous epithelium layer, reduced number of spermatogenic cells, interstitial tissue edema, and a qualitative reduction in the number of interstitial cells and hematoxylin-eosin stained cytoplasm in the untreated group. The transmission electron microscope revealed loose structure of seminiferous epithelium, degenerative mitochondria, and increased amounts of lysosome, presence of numerous cytoplasmic vacuolation and chromatin in interstitial cell cytoplasm in the untreated group. The aggregates of heterochromatin around the nuclear membrane and the shrinkage of nucleus were also observed. Compared to the untreated group, these pathological changes were inconspicuous in EDBJD-treated group. Conclusion EDBJD as replenishing yin to tonify kidney herbs can suppress glucocorticoid induced pathological changes in the testes of rats.

The neurovirulent retroviruses FrCasE and Moloney MLV-ts1 cause noninflammatory spongiform neurodegeneration in mice, manifested clinically by progressive spasticity and paralysis. Neurons have been thought to be the primary target of toxicity of these viruses. However the neurons themselves appear not to be infected, and the possible indirect mechanisms driving the neuronal toxicity have remained enigmatic. Here we have re-examined the cells that are damaged by these viruses, using lineage-specific markers. Surprisingly, these cells expressed the basic helix-loop-helix transcription factor Olig2, placing them in the oligodendrocyte lineage. Olig2+ cells were found to be infected, and many of these cells exhibited focal cytoplasmic vacuolation, suggesting that infection by spongiogenic retroviruses is directly toxic to these cells. As cytoplasmic vacuolation progressed, however, signs of viral protein expression appeared to wane, although residual viral RNA was detectable by in situ hybridization. Cells with the most advanced cytoplasmic effacement expressed the C/EBP-homologous protein (CHOP). This protein is up-regulated as a late event in a cellular response termed the integrated stress response. This observation may link the cellular pathology observed in the brain with cellular stress responses known to be induced by these viruses. The relevance of these observations to oligodendropathy in humans is discussed.

Background: Oral mucositis, a debilitating side-effect of chemotherapy, is difficult to prevent or treat. The aim of this study was to characterize the histological and ultrastructural change in the human oral mucosa following cytotoxic chemotherapy. Methods: Oral buccal mucosa biopsies were taken from four volunteers and 20 cancer patients. Each patient had one biopsy prior to chemotherapy and a second biopsy at varying intervals after chemotherapy. Biopsies were assessed histologically and ultrastructurally. Results: Apoptosis increased in the basal layer in the first 3 days after chemotherapy, began to decline at 6 days, but never returned to levels of volunteers by 11 days after treatment. Ultrastructural changes included increased intercellular fibres in basal layer cells, cytoplasmic vacuolation, loss of membrane contact with neighboring cells, multinucleation of suprabasal cells and loss of cellular cytoplasm. These changes persisted in prechemotherapy biopsies in patients who had prior chemotherapy. Conclusions: Apoptosis occurs early, and persists in the basal layer of the buccal mucosa after chemotherapy. Ultrastructural changes were present and remained up to 11 days after chemotherapy.

A 31-year-old woman presented with a pleomorphic xantho-astrocytoma (PXA) manifesting as epilepsy. The tumour was partially resected. Histological examination revealed cellular pleomorphism and cytoplasmic vacuolation consistent with PXA, but no mitoses, necrosis, or endothelial proliferation. Follow-up neuro-imaging showed the residual tumour had grown rapidly with dissemination in the spinal cord. The recurrent lesion was totally resected and was shown to be glioblastoma. The patient has survived without signs of recurrence for 36 months after adjuvant radiochemotherapy. The biological behaviour of PXA cannot be predicted based on the histological features and careful follow up is essential.