Abnormal Histological Changes Research Articles

The Impact of Tamoxifen Usage in Breast Cancer Patients on the Development of Histopathological Lesions in the Cervix Uteri.

Background and Objectives: The purpose of the present study was to compare the results of colposcopic biopsies in patients with breast cancer and those who tested positive for HPV in cervix uteri cytological screenings, with a control group of HPV-positive individuals without breast cancer. Additionally, through this study, we aimed to investigate the impact of tamoxifen treatment, an anti-oestrogen drug used following breast cancer treatment, on histopathological changes. Breast cancer is the most common type of cancer and cause of death in women worldwide. Cervical cancer ranks as the second most prevalent form of cancer among women globally, with prevalence rates ranking just behind those of breast cancer. Human papillomavirus (HPV) positivity is a requirement for the development of cervical cancer, although it is not the sole factor responsible. Materials and Methods: A comparison was made between the histopathological results of 52 patients diagnosed with breast cancer, who tested positive for HPV in routine cervical cytological screenings and underwent colposcopic biopsy, and 230 cases without any abnormalities. A study was conducted to compare healthy individuals between the ages of 30 and 65 who were diagnosed with breast cancer and those who did not have breast cancer. The participants underwent HPV screening as part of the national cervical cytology screening programme. Results: The average age of those diagnosed with breast cancer was 46.73 ± 7.54; in comparison, the average age of participants in the control group was 47.49 ± 7.95. There was no statistically significant difference in age between the two groups (p: 0.530). A total of 51 cases (98.1%) of breast cancer were found to have actively used the anti-oestrogen drug tamoxifen for a duration ranging from at least 6 months to 5 years. One patient (1.9%) in the breast cancer group did not use tamoxifen. During routine cervical cytological screenings, it was observed that both breast cancer cases and healthy cases tested positive for HPV. The most commonly detected types of HPV in both groups were HPV 16 and 18, with rates of 73.1% noted in the breast cancer group and 92.6% noted in the healthy group, results consistent with the rates found in the general population. HPV 16 was found in 58.7% of participants in the control group and 42.3% of participants in the breast cancer group. There was a statistically significant difference between the two groups (p: 0.032). There was no statistically significant difference observed between the two groups in terms of normal, high-grade cervical intraepithelial lesions (HGSILs); low-grade cervical intraepithelial lesions (LGSILs); and chronic cervicitis histopathological lesions based on colposcopic and endocervical biopsy results, smear cytology, and HPV results (p-values of 0.913 and 0.877, respectively). Conclusions: Our study results indicate that tamoxifen treatment, an anti-oestrogen drug administered for chemoprevention purposes in the management of breast cancer, does not lead to an increase in abnormal histological changes in the cervix uteri. In all cases of breast cancer, gynaecological examination and cervical cytological screening should be advised.

Gross and Micro Anatomical Study of Placenta from Normal and Hypertensive Pregnancies

Introduction: The examination of the placenta gives a clear idea of what happened with fetus when it was in the mother’s womb. The changes in placenta of women with pregnancy induced hypertension and normal pregnancies can be compared. Objective: This study was done to find out differences in gross structure and histology between normal and hypertensive placentas. Methods: Placenta from case and control group was collected from the Gynecology and Obstetrics Department of B.P.Koirala Institute of Health Sciences, Dharan. The histology slides were prepared, examined and parameters was collected. Results: The mean weight of placenta in control group was 469.5±148.9gm and in case group was 375.50 ± 109.08gm which was statistically significant. The histological observation of syncytial knot, hyalinized villi, stromal fibrosis, necrosis, hemorrhage and calcification in placenta was significantly higher in case group than that of in normotensive group. Conclusions: It is concluded that, in hypertension complicating pregnancy, with increase of severity, there is decrease in morphology and increase in abnormal histological changes of placenta. So, the reduction in placental morphological parameters and histological changes might be the reason for retarded growth of baby with increased complication of hypertension.

Nephroprotective potential of Spondias mombin against aluminum chloride induced-renal injury in female albino rats

Aluminum chloride (AlCl3) is a toxic to human and animals, and it’s widely distributed in the environment. Spondias mombin is a herbal medicine used as a therapy for several ailment, renal diseases inclusive. This study evaluated the protective potential of spondias monbin against aluminum chloride induced-nephrotoxicity in female albino rat. Fifteen (15) adult female rats were divided into three (3) groups of five rats each. Group I served as negative control and received distilled water and feed. Group II served as positive control and received AlCl3, and group III received aluminum chloride (100mg/kg body weight) and Spondias mombin (100mg/kg body weight) for 14 days. All treatment was given orally and lasted for a period of fourteen days. The result revealed that AlCl3 significantly (p<0.05) increases urea, creatinine, and malondialdehyde (MDA) levels, and reduced renal superoxide dismutase and catalase activity as compared to the control group. The histopathological result showed marked detectable histopathological alternations in the renal tissues including degenerated glomeruli showing wide urinary space, vacuolar degeneration of tubules, and necrosis of cells. However, serum urea, creatinine and malondialdehyde levels were significantly (p<0.05) reduced in the Spondias mombin + AlCl3 administered rats. While, superoxide dismutase and catalase activity were significantly (p<0.05) increased in Spondias mombin + AlCl3 administered rats compared with the control. In addition, no abnormal histological changes were observed in the Spondias mombin + AlCl3 administered rats compared with the AlCl3. The results indicate that Spondias mombin possess nephroprotective potential against AlCl3 induced renal injury via restoring oxidant/antioxidant balance.

Advancing combination treatment with cilostazol and caffeine for Alzheimer's disease in high fat-high fructose-STZ induced model of amnesia

Several studies have suggested that phosphodiesterase (PDE) inhibitors may be a disease-modifying for Alzheimer’s disease (AD). Cilostazol (CSZ) has been shown to be a new treatment for cognitive impairment with limited efficacy. Our aim was to investigate the effect of caffeine on the efficacy of CSZ against STZ-induced type 2 diabetes (T2D)-related cognitive impairment in high fat/high fructose fed rats. The efficacy of low doses of caffeine, CSZ, and CSZ plus caffeine against abnormal behavioral, biochemical, histological, or genetic changes of animal models of AD was examined. Eight weeks treatment with CSZ plus caffeine was more effective than CSZ or caffeine in improving impaired behavioral tests for cognition and memory. Histological examination exhibited a significant augmentation in the efficacy of CSZ by caffeine in protecting neurons from damage in T2D rats. Importantly, CSZ and caffeine normalized the accumulation of Amyloid beta (Aβ-42) and phosphorylated tau protein (p-tau) positive cells in the brain of T2D rats. CSZ or CSZ plus caffeine reversed low glutamate gene expression, elevated cholinesterase level, and elevated caspase-3 activity in T2D rats. Furthermore, CSZ plus caffeine was significantly more effective than CSZ or caffeine in inhibiting the increase in malondialdehyde (MDA) level, total oxidative stress, pro-inflammatory cytokines and glucogen synthase kinase-3 beta (GSK-3β) in the hippocampus of T2D rats. Also, CSZ plus caffeine was more effective than CSZ or caffeine in alleviating insulin resistance and hypercholesterolemia in T2D rats. Our findings suggest the possibility of effective treatment of AD by enhancing the therapeutic potential of CSZ through combined treatment with lower doses of caffeine. The enhancement of CSZ effect by caffeine is attributed to the increased inhibitory effect of CSZ on insulin resistance, GSK-3β activity, hypercholesterolemia, oxidative stress and pro-inflammatory cytokines.

Histopathology of the temporomandibular joint disc: Findings in 30 samples from joints with degenerative disease.

AimThe aim of this study is to show the anatomical and histological features of the displaced temporomandibular joint (TMJ) disc in joints with degenerative disease.MethodsThis study was performed on a total of 30 TMJ discs extracted from 22 patients, who underwent surgical discectomy after failure of conservative non‐surgical treatment regimens to control pain and/or limited range of motion. All joints had imaging signs of an anteriorized disc position and degenerative joint disease. Samples of the extracted discs were stored in formalin, cut into 3 micron‐thick sections imbedded in paraffin and processed with hematoxylin‐eosin.ResultAll the samples present irreversible morphologic and histological alterations. The macroscopical evaluation showed that 14 discs were worn and fragmented in several parts, and one disc was perforated. Morphological alterations with deformation and degenerative signs were shown in all discs, which were all severely worn and compromised. Histologically, various alterations were found, such as pre‐fibrous sclerosis with myxoid degeneration and collagen deposits (N = 25), an increase in fibro‐hyaline and fibrous tissues, with loss of elasticity (N = 25), scattered calcifications (N = 15), and synovial inflammation with microvascular proliferation and increased cellularity, presence of lymphocytes, histiocytes and plasma cells (N = 18). After the intervention, all patients reported decreased pain levels and showed improved function at 6 months.ConclusionThese observations suggest that degenerative joint disease is accompanied by a anteriorized discs featuring abnormal macroscopical and histological changes. From a clinical viewpoint, this may suggest that, when treatment escalation leads to consider TMJ surgery, total discectomy is the most reasonable approach.

Unusual Fatal Outcome Following Administration of a Combination of anti-PD1 and anti-CTLA4 in Metastatic Renal Cell Carcinoma: Liver Toxicity Case Report and a Literature Review

Hepatic dysfunction, in the absence of liver metastases, occurs in 10–15% of renal cell carcinoma (RCC) patients, while immune hepatitis due to anti-CTLA4 and anti-PD1 administration affects about 3–9% and 0.7–1.8% of treated patients, respectively. Liver toxicity following combination therapy (anti-CTLA4 and anti-PD1) is seen in 29% of patients overall and grade 3–4 toxicity in 14% of patients.Stauffer’s syndrome is a rare para-neoplastic phenomenon associated with RCC and characterized by abnormal liver function tests, hepato-splenomegaly and histological changes consistent with non-specific hepatitis. We describe a case of RCC treated with anti-CTLA4 and anti-PD1 therapy resulting in immediate liver toxicity and death after 2 months of progressive hepatic impairment. We hypothesize that high IL-6 levels due to Stauffer’s syndrome might have contributed to immune-related hepatic failure.LEARNING POINTSConsider Stauffer’s syndrome in patients who develop liver toxicity unresponsive to immunotherapy.Evaluate IL-6 as high levels are seen in Stauffer’s syndrome patients undergoing immunotherapy.Consider taking a liver biopsy to assess the severity of liver injury.

Podocyte RNF166 deficiency alleviates diabetic nephropathy by mitigating mitochondria impairment and apoptosis via regulation of CYLD signal

Diabetic nephropathy (DN) is a major cause of renal failure in diabetic patients. RING-finger protein 166 (RNF166), composed of an N-terminal RING domain and C-terminal ubiquitin interaction motif, plays a critical role in mediating various cellular processes. However, its potential in DN has not been investigated. In the present study, we found that DN patients exhibited significantly increased expression of RNF166 in renal tissues compared with the normal individuals, and abundant RNF166 was detected in podocytes. We then showed that podocyte-conditional RNF166 knockout (RNF166cKO) markedly reduced blood glucose levels and ameliorated renal dysfunction in streptozotocin (STZ)-induced diabetic mice. Additionally, abnormal histological changes and podocyte injury were observed in STZ-induced diabetic mice, while being markedly ameliorated by RNF166cKO. Furthermore, podocyte-specific RNF166 deficiency considerably mitigated apoptosis and mitochondrial impairments in glomeruli podocytes of STZ-challenged mice through suppressing Caspase-3 cleavage and improving mitochondrial fission-associated molecules. In vitro studies further confirmed that high glucose (HG) induced mitochondrial dysfunction, along with enhanced releases of Cyto-c from mitochondria and elevated expression of cleaved Caspase-9, contributing to intrinsic apoptosis in podocytes. Intriguingly, these effects triggered by HG were dramatically ameliorated by RNF166 knockout. Mechanistically, we demonstrated that RNF166 directly interacted with cylindromatosis (CYLD), and negatively regulated CYLD expression. Notably, RNF166 knockout-attenuated mitochondrial damage and apoptosis were mainly through CYLD in podocytes upon HG stimulation. Together, all these findings provided new insights into the novel effects of RNF166 on maintaining mitochondrial function and apoptosis in podocytes during DN progression both in vivo and in vitro through interacting with CYLD, indicating that RNF166/CYLD may be an innovative therapeutic target for developing effective strategy against DN development.

Amido-Bridged Nucleic Acid-Modified Antisense Oligonucleotides Targeting SYT13 to Treat Peritoneal Metastasis of Gastric Cancer

Patients with peritoneal metastasis of gastric cancer have dismal prognosis, mainly because of inefficient systemic delivery of drugs to peritoneal tumors. We aimed to develop an intraperitoneal treatment strategy using amido-bridged nucleic acid (AmNA)-modified antisense oligonucleotides (ASOs) targeting synaptotagmin XIII (SYT13) and to identify the function of SYT13 in gastric cancer cells. We screened 71 candidate oligonucleotide sequences according to SYT13-knockdown efficacy, in vitro activity, and off-target effects. We evaluated the effects of SYT13 knockdown on cellular functions and signaling pathways, as well as the effects of intraperitoneal administration to mice of AmNA-modified anti-SYT13 ASOs. We selected the ASOs (designated hSYT13-4378 and hSYT13-4733) with the highest knockdown efficiencies and lowest off-target effects and determined their abilities to inhibit cellular functions associated with the metastatic potential of gastric cancer cells. We found that SYT13 interfered with focal adhesion kinase (FAK)-mediated intracellular signals. Intraperitoneal administration of hSYT13-4378 and hSYT13-4733 in a mouse xenograft model of metastasis inhibited the formation of peritoneal nodules and significantly increased survival. Reversible, dose- and sequence-dependent liver damage was induced by ASO treatment without causing abnormal morphological and histological changes in the brain. Intra-abdominal administration of AmNA-modified anti-SYT13 ASOs represents a promising strategy for treating peritoneal metastasis of gastric cancer.

Histomorphometric Effects of Smokeless Tobacco on Submandibular Gland in Albino Rat

Background: Use of the smokeless tobacco is a major public health problem. Oral mucosal hyper keratinization occurs due to smokeless form of tobacco. Objective: To determine the Submandibular Gland injuries induced by smokeless tobacco in Albino Rat. Study Design: Experimental study. Settings: Department of Oral biology, Liaquat University of Medical & Health Sciences, Jamshoro-Pakistan. Duration: From November 1, 2015 to April 30, 2016. Methodology: Aalbano healthy rats were used to observe smokeless tobacco effects on submandibular glands. After initial weight record, rats were placed in three groups (A, B, C); Group-A (control group), group-B and group-C were fed with tobacco; non-smokeless, smokeless 5%, and smokeless 10%, respectively. During experiment, weight gain was recorded weekly and sub-mandibular gland weight was measured at the end of the trial. T-test was applied to analyze the data. H & E stain and reticulin stain were used to observed structural integrity of submandibular gland. All the data was recorded in the self-made proforma. Results: Overall body weight and submandibular weight were decreased in B and C groups as compared to control group. In group A, seromucinous acini was seen in parenchymal tissue, cuboidal epithelium showed duct line and red blood cells distended vessels. Stromal changes, narrow duct lumen and reasonable damage in parenchymal tissue with atrophy were detected in group B. Stromal tissues increased and atrophy of acini were observed in H and E stain during histological study. Further, as compared to control groups, in group B and C under reticulin stain and stromal tissues were enlarged with pragmatic vascular collapse. Conclusion: This study revealed abnormal histological changes in submandibular gland of albino female rats by oral use of smokeless tobacco.

Light and Electron Microscopic Study on the Possible Protective Effect of Melatonin on Formaldehyde Induced Testicular Damage in Adult Albino Rats

Background: Formaldehyde is a chemical compound used in industrial field and hospitals. Melatonin is an endogenous hormone released by the pineal gland. Melatonin has an antioxidant effects. This work aimed to detect the abnormal histological changes in the testis of adult albino rats induced by formaldehyde and the possible protective role of using a melatonin drug in combination with formaldehyde.Material and Methods: Thirty adult albino rats weighing 180-220 gm were divided into three groups; Group I (control): Rats of this group were intraperitoneally injected with 5% ethanol once every other day for one month. Group II (Formaldehyde treated group): Rats were intraperitoneally injected with formaldehyde at a dose of 10 mg/kg body weight once every other day for one month. Group III (Formaldehyde and melatonin treated group): Rats were intraperitoneally injected with formaldehyde at a dose of 10mg/kg body weight and after one hour they were intraperitoneally injected with melatonin at a dose of 25 mg/kg body weight. Both drugs were injected once every other day for one month. The rats were sacrified, the testes were dissected, processed for light microscopy using) H&E ,Masson’s trichrome, PAS(, electron microscope, morphometric and statistical measurements were also done.Results: Examination of formaldehyde treated rats revealed thickening of tunica albuginea, tubular degeneration, loss of normal architecture of tubules, marked increase in the collagen fibers deposition, degenerated nuclei with indented and thickened nuclear envelope, ballooned mitochondria, karyolitic nucleus of a head of a sperm. Rats treated with melatonin together with formaldehyde showed obvious improvement in the previous alterations.Conclusion: It could be concluded that formaldehyde induced histological alterations in the testis of albino rats that could be improved by using melatonin, so, it is essential to supply workers in anatomy department and food industries with melatonin but the human application needs further studies to adjust the dose and the route of administration

Chitosan from crustacean shell waste and its protective role against lead toxicity in Oreochromis mossambicus

In the current study heavy metal removing capability and antioxidant properties of chitosan supplemented diet tested in lead poisoning induced Oreochromis mossambicus in comparison with and standard fish diet. O. mossambicus fishes weighed (20 ± 2gm) were purchased from a local commercial fish pond and acclimated to the laboratory conditions for 10 days. After that fish were dived into four groups, each group received respective feed throughout the experimental period. The fish fed with standard diet exhibited drastic weakening of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GR), glutathione peroxidase (GPx), ascorbic acid, α- tocopherol and β-carotene and also displayed abnormal histological changes in gills, liver, and intestine. The fish fed with a chitosan supplemented diet for 10 days showed substantial enhancements in antioxidant levels and also normal histological structures of organs in the fish.

Progressive cardiac arrhythmias and ECG abnormalities in the Huntington's disease BACHD mouse model.

Huntington's disease (HD) is a dominantly inherited neurodegenerative disease. There is accumulating evidence that HD patients have increased prevalence of conduction abnormalities and compromised sinoatrial node function which could lead to increased risk for arrhythmia. We used mutant Huntingtin (mHTT) expressing bacterial artificial chromosome Huntington's disease mice to determine if they exhibit electrocardiogram (ECG) abnormalities involving cardiac conduction that are known to increase risk of sudden arrhythmic death in humans. We obtained surface ECGs and analyzed arrhythmia susceptibility; we observed prolonged QRS duration, increases in PVCs as well as PACs. Abnormal histological and structural changes that could lead to cardiac conduction system dysfunction were seen. Finally, we observed decreases in desmosomal proteins, plakophilin-2 and desmoglein-2, which have been reported to cause cardiac arrhythmias and reduced conduction. Our study indicates that mHTT could cause progressive cardiac conduction system pathology that could increase the susceptibility to arrhythmias and sudden cardiac death in HD patients.

Molecular, biochemical and histopathological studies on the ameliorative effect of vitamin C on the renal and muscle tissues of Nile tilapia fish ( Oreochromis niloticus ) affected by the usage of engine oil

The present study was performed to evaluate the effect of vitamin C on the performance of Nile tilapia (Oreochromis niloticus) affected by the usage of engine oil. A total of 120 tilapia fish were randomly divided into four equal groups according to dietary treatments applied for 3 weeks: group I (control); group II was exposed to engine oil; group III was exposed to engine oil and supplemented with vitamin C: and group IV was fed only a diet supplemented with vitamin C. According to our results, the group exposed to engine oil (II) showed an induced elevation of kidney function parameters, an upregulation of CYP1A1 mRNA expression level, a reduction in antioxidant status (SOD, GSH) and severe abnormal histological and ultra-structural changes in the head kidney, trunk kidney and muscle tissue. Supplementation of group III with vitamin C ameliorated the toxic effect induced by engine oil through improvement of kidney function parameters, elevation of the antioxidant status of tissue and improvement of the histological images of renal and muscle tissues. In conclusion, vitamin C has the ability to ameliorate engine oil oxidative stress toxicity in Nile tilapia.

Altered expression of leptin and leptin receptor in the development of immune-mediated aplastic anemia in mice.

The current study aimed to explore the levels of leptin (LEP) and LEP receptor (LEP-R) on the progression of aplastic anemia (AA) with bone marrow fat conversion. An AA model was developed by infusing C57BL/6 lymph node cells into BALB/c mice. At 0, 3, 6, 9, 12, 15 and 18 days after modeling, routine blood counts, bone marrow biopsy slides, lymphocyte subsets (CD4+ and CD8+ T cells) and cytokine levels [including interleukin (IL)-2, IL-4, IL-5 and interferon-γ] were assessed. LEP and LEP-R levels in peripheral blood serum, mesenchymal stem cells (MSCs) and bone marrow were also analyzed by enzyme-linked immunosorbent assay, polymerase chain reaction and immunohistochemistry. The relevance of LEP, LEP-R and other factors was analyzed by Pearson's correlation analysis. Peripheral pancytopenia (reduced count of white blood cells, red blood cells, hemoglobin and platelets), abnormal immune factor levels and histological changes in bone marrow sections were detected in the AA model mice, suggesting that these mice mimicked the pathological changes commonly observed in AA. In addition, following the establishment of AA, the LEP level was gradually increased and the LEP-R level was reduced in the mice over time (P<0.05). The expression of adipogenic genes, including CCAAT/enhancer-binding protein (C/EBP)α, C/EBPβ and peroxisome proliferator-activated receptor γ, was markedly increased, while the expression of the osteogenic gene runt-related transcription factor 2 was reduced compared with the levels in the control group (P<0.05). Taken together, damage to LEP-R may lead to dysregulation of LEP and the enhancement of MSCs to differentiate into adipocytes, resulting in excessive fat in bone marrow of AA patients.

The positive effect of metformin and metronidazole on the diabetic rats experimentally

Diabetes mellitus is considering most serious disease of endocrine, it affecting large number of people in worldwide. This study was performed to insured the effect of combination of metformin and metronidazole on disorder in metabolic that concomitant with injection of alloxan IP induced diabetes in rats. In this study forty male rats: divided into four groups including control group G1, alloxn group (150 mg/kg single dose) G2, alloxn group orally treated with metformin (150mg/kg/BW) G3, and alloxn group orally treated with metformin (150mg/kg/BW) and metronidazole (500mg/kg/BW) G4. The experiment last for 14 days. The result shows marked increase in MDA, glucose and also in liver enzymes, lipid profiles and even observed disorder in kidney function test by increased in the creatinine, urea, and uric acid levels. In addition to study the histological changes in diabetic liver of rats characterized by kupffer cells activation, dilation and congestion of central vein and hepatic sinusoids. Administration of metformin and combination of metformin and metronidazole, result in significant reduction return abnormal parameters to the normal values. Also correct the abnormal histological changes of liver.

Impact of the Di(2-Ethylhexyl) Phthalate Administration on Trace Element and Mineral Levels in Relation of Kidney and Liver Damage in Rats.

Di(2-ethylhexyl) phthalate (DEHP) is a widely used synthetic polymer in the industry. DEHP may induce reproductive and developmental toxicity, obesity, carcinogenesis and cause abnormal endocrine function in both human and wildlife. The aim of this study was to investigate trace element and mineral levels in relation of kidney and liver damage in DEHP-administered rats. Therefore, prepubertal male rats were dosed with 0, 100, 200, and 400mg/kg/day of DEHP. At the end of the experiment, trace element and mineral levels, glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6-PGD), glutathione reductase (GR) and glutathione S-transferase (GST) enzyme activities were evaluated in the serum, liver, and kidney samples of rats. Furthermore, serum clinical biochemistry parameters, organ/body weight ratios and histological changes were investigated to evaluate impact of DEHP more detailed. Our data indicated that sodium (Na), calcium (Ca), potassium (K), lithium (Li), rubidium (Rb) and cesium (Cs) levels significantly decreased, however iron (Fe) and selenium (Se) concentrations significantly increased in DEHP-administered groups compared to the control in the serum samples. On the other hand, upon DEHP administration, selenium concentration, G6PD and GR activities were significantly elevated, however 6-PGD activity significantly decreased compared to the control group in the kidney samples. Decreased G6PD activity was the only significant change between anti-oxidant enzyme activities in the liver samples. Upon DEHP administration, aberrant serum biochemical parameters have arisen and abnormal histological changes were observed in the kidney and liver tissue. In conclusion, DEHP may induce liver and kidney damage, also result abnormalities in the trace element and mineral levels.

Protective role of Diospyros lotus on cisplatin-induced changes in sperm characteristics, testicular damage and oxidative stress in rats.

The aim of this study was to investigate the protective effect of Diospyros lotus (DL) on cisplatin (CP)-induced testicular damage in male rats. Twenty-eight male rats were randomly divided into four groups: group 1 - control, given isotonic saline solution; group 2 - CP 7 mg kg(-1) given intraperitoneally as single dose; group 3 - DL 1000 mg kg(-1) per day given orally for 10 days; group 4 - CP and DL given together at the same doses. CP caused a significant increase in thiobarbituric acid-reactive substances (TBARS) level and a significant decrease in superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione (GSH) levels in rats testis tissues compared to the control group. CP caused a significant increase in lipid peroxidation in testis tissues compared to the control group, whereas DL led to a significant increase in SOD and GSH levels. However, there were no statistically significant changes in GPx and CAT levels. In addition, serum testosterone levels, sperm concentration and sperm motility were significantly decreased, but abnormal sperm rate and histological changes were increased with CP. However, these effects of CP on sperm parameters, histological changes and the tissue weights were eliminated by DL treatment. In conclusion, our study showed that the reproductive toxicity caused by CP may be prevented by DL treatment.

Isolation and characterization of a "phiKMV-like" bacteriophage and its therapeutic effect on mink hemorrhagic pneumonia.

The objective of this study was to investigate the potential of using phages as a therapy against hemorrhagic pneumonia in mink both in vitro and in vivo. Five Pseudomonas aeruginosa (P. aeruginosa) strains were isolated from lungs of mink with suspected hemorrhagic pneumonia and their identity was confirmed by morphological observation and 16S rDNA sequence analysis. Compared to P. aeruginosa strains isolated from mink with hemorrhagic pneumonia in 2002, these isolates were more resistant to antibiotics selected. A lytic phage vB_PaeP_PPA-ABTNL (PPA-ABTNL) of the Podoviridae family was isolated from hospital sewage using a P. aeruginosa isolate as host, showing broad host range against P. aeruginosa. A one-step growth curve analysis of PPA-ABTNL revealed eclipse and latent periods of 20 and 35 min, respectively, with a burst size of about 110 PFU per infected cell. Phage PPA-ABTNL significantly reduced the growth of P. aeruginosa isolates in vitro. The genome of PPA-ABTNL was 43,227 bp (62.4% G+C) containing 54 open reading frames and lacked regions encoding known virulence factors, integration-related proteins and antibiotic resistance determinants. Genome architecture analysis showed that PPA-ABTNL belonged to the “phiKMV-like Viruses” group. A repeated dose inhalational toxicity study using PPA-ABTNL crude preparation was conducted in mice and no significantly abnormal histological changes, morbidity or mortality were observed. There was no indication of any potential risk associated with using PPA-ABTNL as a therapeutic agent. The results of a curative treatment experiment demonstrated that atomization by ultrasonic treatment could efficiently deliver phage to the lungs of mink and a dose of 10 multiplicity of infection was optimal for treating mink hemorrhagic pneumonia. Our work demonstrated the potential for phage to fight P. aeruginosa involved in mink lung infections when administered by means of ultrasonic nebulization.

Biological Parameters for Evaluating the Toxic Potency of Petroleum Ether Extract of Wattakaka volubilis in Wistar Female Rats.

Objectives:The present study investigated the toxic properties of petroleum ether extract of Wattakaka (W.) volubilis in Wistar female rats.Methods:An in vitro brine shrimp lethality bioassay was studied in A. Salina nauplii, and the lethality concentrations were assessed for petroleum ether extract of W. volubilis. A water soluble portion of the test extract was used in different concentrations from 100-1000 μg/mL of 1 mg/mL stock solution. A 24-hours incubation with a 1-mL aliquot in 50 mL of aerated sea water was considered to calculate the percentage rate of dead nauplii with test extract administration against a potassium-dichromate positive control. The acute and the sub-acute toxicities of petroleum ether extract of W. volubilis were evaluated orally by using gavage in female Wistar rats. Food and water intake, body weight, general behavioral changes and mortality of animals were noted. Toxicity or death was evaluated following the administration of petroleum ether extract for 28 consecutive days in the female rats. Serum biochemical parameters, such as alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, total cholesterol, triglyceride, total protein, glucose, urea, creatinine, sodium, potassium and α-amylase levels, were measured in the toxicity evaluations. Pathological changes in isolated organs, such as the liver, kidneys, and pancreas, were also examined using hematoxylin and eosin dye fixation after the end of the test extract’s administration.Results:The results of the brine-shrimp assay indicate that the evaluated concentrations of petroleum ether extract of W. volubilis were found to be non-toxic. In the acute and the sub-acute toxicity evaluations, no significant differences were observed between the control animals and the animals treated with extract of W. volubilis. No abnormal histological changes were observed in any of the animal groups treated with petroleum ether extract of W. volubilis.Conclusion:These results suggest that petroleum ether extract of W. volubilis has a non-toxic effect in Wistar female rats.

Echinacoside ameliorates D-galactosamine plus lipopolysaccharide-induced acute liver injury in mice via inhibition of apoptosis and inflammation

Objective. This study aimed to investigate the protective effects of echinacoside, one of the phenylethanoids isolated from the stems of Cistanche salsa, a Chinese herbal medicine, on D-galactosamine (GalN) and lipopolysaccharide (LPS)-induced acute liver injury in mice. Methods. We administered GalN (650 mg/kg) together with LPS (30 μg/kg) to mice by intraperitoneal injection to induce acute liver damage. Echinacoside (60 mg/kg) was given intraperitoneally to mice at 1 h prior to GalN/LPS exposure. Mice were sacrificed at different time points following GalN/LPS treatment, and the liver and blood samples were collected for future analysis. Results. It showed that GalN/LPS treatment produced severe hepatic injury, evidenced by significantly elevated plasma alanine aminotransferase (ALT) levels and abnormal histological changes such as hepatocyte necrosis or apoptosis, hemorrhage, fatty degeneration, and neutrophil infiltration. Notably, pretreatment with echinacoside remarkably improved the survival rate of GalN/LPS-treated mice and attenuated acute hepatotoxicity, as demonstrated by decreased ALT levels and improved histological signs. Echinacoside shows both anti-apoptotic and anti-inflammatory properties, characterized by a substantial inhibition of hepatocyte apoptosis and a significant reduction in the inflammatory markers, including myeloperoxidase, extracellular nucleosomes, high-mobility group box 1, and inflammatory cytokines in the plasma of mice, which may be important mechanisms related to its protective effect. Conclusion. Our results suggest that echinacoside can provide a pronounced protection against GalN/LPS-induced acute liver injury in mice, which may complement the available strategies for management of acute liver damage in clinical settings.