Histopathological Examination Of Brain Research Articles

ROS dependent neurotoxicity, genotoxicity & histopathological alterations triggered by β-cyfluthrin, a synthetic pyrethroid

Abstract Given the widespread use of pyrethroids in home and agriculture, it becomes important to evaluate their potential effects on humans. This study was taken up to gain an insight into the genotoxicity and behavioural toxicity of β-cyfluthrin when administered orally to male Swiss albino mice. Further, the activity of acetyl cholinesterase and antioxidant enzymes was estimated and histopathological examination of brain was performed. It was found that 28 days oral exposure to β-cyfluthrin caused genotoxicity by damaging the DNA as seen by a decline in mitotic index, increase in aberrant cells, tail length and tail intensity. Neuromuscular coordination and learning ability of mice was adversely affected. Concomitantly, a reduction in acetylcholinesterase and antioxidant enzymes occur indicating oxidative stress caused by the pesticide. Histopathological examination of brain revealed structural alterations in the hippocampus region. Thus, it may be concluded that β-cyfluthrin exposure caused neurobehavioural alterations, genotoxicity, oxidative stress and histopathological changes in mice.

The anti-Alzheimer effect of telmisartan in a hyperglycemic ovariectomized rat model; role of central angiotensin and estrogen receptors

The central renin angiotensin system (RAS) is implicated in Alzheimer's disease (AD). Here, induction of experimental AD simulation was performed by D-galactose (D-Gal) injection to ovariectomized (OVX) rats fed on high fat high fructose diet (HFFD). Telmisartan administration to OVX/HFFD/D-Gal rats lowered the expression of hippocampal angiotensin 1 and 2 receptors and glucose transporter 2 in addition to lowering of the peripheral and central glucose levels. Furthermore, it improved cognitive impairment and suppressed hippocampal amyloidogenic markers including amyloid-beta level, phosphorylated tau protein and beta site amyloid precursor protein cleaving enzyme 1 expression, while elevated levels of insulin degrading enzyme and recovered permeability of blood brain barrier (BBB). In addition, it inhibited hippocampal oxido-nitrosative stress as well as neuroinflammatory and apoptotic biomarkers. Telmisartan improved memory and cognitive impairment as shown in the behavioral Morris water maze, Y-maze, novel object recognition and open field tests in addition to amelioration of depressive like behavior as shown in forced swimming test. Histopathological examination of brain and immune expression of glial fibrillary acidic protein were also improved together with astrogliosis improvement. In conclusion, telmisartan improved memory and cognitive impairment, recovered amyloidogenesis-hyperglycemic axis, astrogliosis, integrity of BBB, memory deficit and oxidonitrosative stress induced in OVX/HFFD/D-Gal rats.

Toxicological evaluation of the ethanol extract of <i>Lophira alata</i> (Ochnaceae) stem bark in rats

Though Lophira alata is used in ethnomedicine for the management of a host of central nervous and systemic diseases, the toxicity profile has not been investigated. This study evaluated the toxicological profile of the ethanol extract of Lophira alata stem bark in rats. The mean lethal dose was determined. Animals were treated with 50-800 mg/kg of the ethanol extract for four weeks after which body weight/organ ratio, haematological, biochemical (renal and hepatic) and lipid profile of test animals were evaluated. Changes in body weight and histopathological examination of brains, kidneys and livers were also carried out. Lower doses (50-400 mg/kg) did not affect body weight, organ/body weight ratio, hepatic, renal, haematological, lipid profile and morphology of organs of test animals. The highest dose affected creatinine levels, serum proteins and induced some histopathological changes. Lophira alata is relatively safe at low doses but high doses of Lophira alata should be used with caution.Keywords: Lophira alata; Toxicity; Lipd profile; Haematological indices

Toxicological Effects and Histopathological Alterations of Diazinon and Alpha Cypermethrin on Male Albino Rats

Background: In Egypt, risk assessment of pesticides usage and pesticides misuse to protect plants and increase productivity connected with health hazards and pollution problems have been of public interest. Around the world three million acute poisoning cases from pesticide exposure annually report.
 Aim of study was to investigate the histopathological alterations, biochemical and genotoxicity adverse effects of synthetic insecticides Diazinon (organophosphorus) and alpha cypermethrin (pyrethroid) which are using for agricultural and public health applications on male albino rats.
 Methods: Twenty one albino rats were detached into control and two experimental groups. The experimental groups were treated with Diazinon (DIZ) and Alpha-cypermethrin (α-CYP) at sub-lethal dose (1/10 LD50 36.51 and 1.4 mg/kg body weight, respectively) by oral treatment for consecutively 28-days. The male albino rats in control treatment were put in similar surrounding conditions and treated with 5 ml /Kg tap water. Albino rats were killed after completing exposure of 28-days, liver and brain samples were dissected out for processing and sectioning examinations.
 Results: The obtained results revealed that both tested insecticides induced oxidative damage as appearance by a significant raise in malondialdehyde (MDA) indicating lipid peroxidation and deoxyribonucleic acid (DNA) damage indicating genotoxicity in the liver and brain. Besides, increase in GSH level and decline in enzymatic antioxidants (GST, CAT, SOD) activities were observed in liver. Marked increase was noticed in GSH levels and GST activity in brain whereas CAT and SOD antioxidant enzymes activity were significantly reduced. Histopathological studies in brain and liver revealed multiplied focal hepatic necrosis, hydropic degeneration of the hepatocytes and portal infiltration inflammatory cells in the liver. Necrosis of neurons, neuronophagia, focal gliosis and cellular oedema, congestion of cerebral blood vessel were noticed in the brain of exposed rats.
 Conclusion: The histopathological examination of brain and liver tissues and oxidative damage biomarkers showed adverse effects of DIZ or α-CYP insecticides at the tested dose (1/10 LD50).

Exacerbation of Toluene’s Neuro- and Hepato-Toxicity by Amiodarone or Chlorpropamide: Involvement of Oxidative Stress

Volatile solvent abuse is an important health problem and results in serious injury to the central nervous system. Neuroprotective effects were reported for the sulfonylurea group of drugs and for the anti-arrhythmic agent amiodarone, and these drugs have a K+ channel-blocking effect. The K+ channels are of interest for their ability to modulate brain damage. The aim of this study was to investigate the effect of amiodarone and chlorpropamide on the development of oxidative stress and brain and liver damage induced by toluene injection in rats. Toluene (900 mg/kg) was intraperitoneally (ip) administered alone or in combination with amiodarone or chlorpropamide (18 or 36 mg/kg, orally) once a day for 2 consecutive days. The brain and liver content of malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide (NO), and the activity of paraoxonase-1 (PON-1) were determined. In addition, butyrylcholinesterase (BChE) and the concentration of the anti-apoptotic protein (Bcl-2) were determined in brain homogenates. Histopathological examination of brain and liver sections was also performed. Results showed that compared to controls, toluene resulted in increased oxidative stress in the brain and liver tissues. MDA and NO concentrations were markedly raised along with decreased levels of GSH and PON-1 activity. Toluene also inhibited BChE activity and decreased Bcl-2 level in the brain tissue. The biochemical changes induced by toluene were aggravated by the administration of either amiodarone or chlorpropamide. Rats treated with toluene exhibited dead neurons, perineuronal vacuolations, infiltrative cells, glial cells, and degeneration of some Purkinje cells. In the liver, massive hepatic inflammatory infiltrate, hemorrhage, vacuolar degeneration, apoptosis, and degeneration of hepatocytes were observed. The co-administration of either amiodarone or chlorpropamide caused dose-dependent exacerbation of the toluene-induced pathological changes. These findings suggest the involvement of oxidative stress in the neuro- and hepato-toxicity by toluene and imply a greater toxicity in toluene abusers treated with either amiodarone or chlorpropamide.

Clinicopathologic Findings of CARS2 Mutation

ObjectivesWe describe a 13-year-old girl with a past medical history of epilepsy, intellectual impairment, dysphagia with gastric tube dependence, and autism spectrum disorder who presented with focal status epilepticus. MethodsVideo-electroencephalography revealed left occipital pseudoperiodic epileptiform discharges and frequent seizures originating from the left hemisphere. The seizure was refractory to antiepileptic medications and pharmacologic coma. Subsequently, left occipital lobectomy was done. Extensive evaluation including whole exome sequencing, histopathologic examination of brain and muscle samples, mitochondrial DNA content analysis of tissue sample was completed to detect the etiology. ResultsSkeletal muscle mitochondrial DNA content (qPCR) analysis showed approximately 37% of the mean value of age and tissue matched control group consistent with a mitochondrial depletion syndrome. Microscopic examination of the brain showed cortical abnormalities that largely consisted of infarct-like pathology in a laminar manner, abnormalities of neuronal distribution, and white matter changes. Compound heterozygous mutations of the CARS2 gene were identified by whole exome sequencing; V52G variant [p.Val52Gly (GTG>GGG):c.155 T>G in exon 1] was inherited from the mother and T188M variant[p.Thr188Met (ACG>ATG): c.563 C>T in exon 5] was inherited from the father. ConclusionThis is the first detailed clinicopathologic description of the Alpers-Huttenlocher syndrome phenotype from CARS mutations.

The Effect of Passive Smoking for Different Periods on Histopathological Central Nervous System of Male Mice Mus musculus

The research aims to show the histopathological changes caused by passive smoking in the central nervous system tissues. Laboratory animals were offered for (10, 20) weeks for a period of passive smoking (2,4) hours per day. Histopathological examination of brain and spinal cord showed the presence of degeneration and necrotic neurons in the brain tissue and spinal cord in addition to vacuolation and heavy hemorrhage in the brain tissue and congestion of blood vessels of the brain and spinal cord and clarity clot inside the blood vessel of the brain tissue.

Preventive effects of cannabis on neurotoxic and hepatotoxic activities of malathion in rat

Objective: To investigate the effect of Cannabis sativa extract on the development of neuro- and hepato-toxicity caused by malathion injection in rats. Methods: The extract of Cannabis sativa was obtained from the plant resin by chloroform treatment. Δ-Tetrahydrocannabinol content of the extract (20%) was quantified using gas chromatography–mass spectrometry. The doses of cannabis extract were expressed as Δ -tetrahydrocannabinol content of 10 or 20 mg/kg. Malathion (150 mg/kg) was intraperitoneally administered followed after 30 min by the cannabis extract (10 or 20 mg/kg, subcutaneously). Rats were euthanized 4 h later. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide and paraoxonase-1 (PON-1) activity were determined in brain and liver. Brain 5-lipoxygenase and butyrylcholinesterase (BChE) activity were measured as well. Histopathological examination of brain and liver tissue was also performed. Results: Compared to controls, malathion resulted in increased oxidative stress in brain and liver. MDA and nitric oxide concentrations were significantly increased (P

Grape Seed Extract Alone or Combined with Atropine in Treatment of Malathion Induced Neuro- and Genotoxicity

The aim of this study was to investigate the effect of treatment with grape seed extract (GSE) on the neurotoxic and genotoxic effects of acute malathion exposure. Rats received malathion (150 mg/kg by i.p. injection) for two successive days alone or combined with GSE at doses of 150 or 300 mg/kg, orally or with GSE at 300 mg/kg and atropine at a dose of 2 mg/kg, i.p. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, paraoxonase (PON1) were determined in cortex, striatum, and rest of brain tissue (subcortex). Interleukin-1β (IL-1β), and butyrylcholinesterase (BChE) activities were determined in brain regions. Cytogenetic analyses for chromosomal aberrations in somatic and germ cells, micronucleus test, Comet assay, DNA fragmentation of liver cells and histopathological examination of brain and liver sections were also performed. Malathion resulted in an increase in MDA, nitric oxide; a decrease in GSH and PON1 activity in different brain regions. IL-1β increased, while BChE activity decreased in brain after the administration of malathion. The insecticide also caused marked structural and numerical chromosomal aberrations and increased liver DNA fragmentation. The Comet assay showed a significant increase in DNA damage of peripheral blood lymphocytes. These effects of malathion were alleviated with the administration of GSE alone or combined with atropine. Addition of atropine to treatment with GSE was associated with significant decrease in MDA, BChE and chromosomal aberrations compared with GSE only treatment. Our data indicate that GSE protects against malathion neurotoxic and genotoxic effects, most likely through reducing brain oxidative stress and inflammatory response.

Nitric oxide synthase inhibitors protect against brain and liver damage caused by acute malathion intoxication.

To investigate the effect of NG-nitro-l-arginine methyl ester (l-NAME), a non-selective nitric oxide synthase (NOS) inhibitor, and 7-nitroindazole (7-NI), a selective neuronal NOS inhibitor, on oxidative stress and tissue damage in brain and liver and on DNA damage of peripheral blood lymphocytes in malathion intoxicated rats. Malathion (150mg/kg) was given intraperitoneally (i.p.) along with l-NAME or 7-NI (10 or 20mg/kg, i.p.) and rats were euthanized 4h later. The lipid peroxidation product malondialdehyde (MDA), nitric oxide (nitrite), reduced glutathione (GSH) concentrations and paraoxonase-1 (PON-1) activity were measured in both brain and liver. Moreover, the activities of glutathione peroxidase (GPx) acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), total antioxidant capacity (TAC), glucose concentrations were determined in brain. Liver enzyme determination, Comet assay, histopathological examination of brain and liver sections and inducible nitric oxide synthase (iNOS) immunohistochemistry were also performed. (i) Rats treated with only malathion exhibited increased nitric oxide and lipid peroxidation (malondialdehyde) accompanied with a decrease in GSH content, and PON-1 activity in brain and liver. Glutathione peroxidase activity, TAC, glucose concentrations, AChE and BChE activities were decreased in brain. There were also raised liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and increased DNA damage of peripheral blood lymphocytes (Comet assay). Malathion caused marked histopathological changes and increased the expression of iNOS in brain and liver tissues. (ii) In brain of malathion-intoxicated rats, l-NAME or 7-NI resulted in decreased nitrite and MDA contents while increasing TAC and PON1 activity. Reduced GSH and GPx activity showed an increase by l-NAME. AChE activity increased by 20mg/kg l-NAME and 10mg/kg 7-NI. AChE activity decreased by the higher dose of 7-NI while either dose of 7-NI resulted in decreased BChE activity. (iii) In liver of malathion-intoxicated rats, decreased MDA content was observed after l-NAME or 7-NI. Nitrite level was unchanged by l-NAME but increased after 7-NI which also resulted in decreased GSH concentration and PON1 activity. Either inhibitor resulted in decreased liver ALT activity. (iv) DNA damage of peripheral blood lymphocytes was markedly inhibited by l-NAME or 7-NI treatment. (v) iNOS expression in brain and liver decreased by l-NAME or 7-NI. (vi) More marked improvement of the histopathological alterations induced by malathion in brain and liver was observed after 7-NI compared with l-NAME. In malathion intoxicated rats, the neuronal NOS inhibitor 7-NI and to much less extent l-NAME were able to protect the brain and liver tissue integrity along with improvement in oxidative stress parameters. The decrease in DNA damage of peripheral blood lymphocytes by NOS inhibitors also suggests the involvement of nitric oxide in this process.

A study of diaphyseal nutrient foramina in human tibia

To investigate the effect of NG-nitro-l-arginine methyl ester (l-NAME), a non-selective nitric oxide synthase (NOS) inhibitor, and 7-nitroindazole (7-NI), a selective neuronal NOS inhibitor, on oxidative stress and tissue damage in brain and liver and on DNA damage of peripheral blood lymphocytes in malathion intoxicated rats.Malathion (150 mg/kg) was given intraperitoneally (i.p.) along with l-NAME or 7-NI (10 or 20 mg/kg, i.p.) and rats were euthanized 4 h later. The lipid peroxidation product malondialdehyde (MDA), nitric oxide (nitrite), reduced glutathione (GSH) concentrations and paraoxonase-1 (PON-1) activity were measured in both brain and liver. Moreover, the activities of glutathione peroxidase (GPx) acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), total antioxidant capacity (TAC), glucose concentrations were determined in brain. Liver enzyme determination, Comet assay, histopathological examination of brain and liver sections and inducible nitric oxide synthase (iNOS) immunohistochemistry were also performed.(i) Rats treated with only malathion exhibited increased nitric oxide and lipid peroxidation (malondialdehyde) accompanied with a decrease in GSH content, and PON-1 activity in brain and liver. Glutathione peroxidase activity, TAC, glucose concentrations, AChE and BChE activities were decreased in brain. There were also raised liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and increased DNA damage of peripheral blood lymphocytes (Comet assay). Malathion caused marked histopathological changes and increased the expression of iNOS in brain and liver tissues. (ii) In brain of malathion-intoxicated rats, l-NAME or 7-NI resulted in decreased nitrite and MDA contents while increasing TAC and PON1 activity. Reduced GSH and GPx activity showed an increase by l-NAME. AChE activity increased by 20 mg/kg l-NAME and 10 mg/kg 7-NI. AChE activity decreased by the higher dose of 7-NI while either dose of 7-NI resulted in decreased BChE activity. (iii) In liver of malathion-intoxicated rats, decreased MDA content was observed after l-NAME or 7-NI. Nitrite level was unchanged by l-NAME but increased after 7-NI which also resulted in decreased GSH concentration and PON1 activity. Either inhibitor resulted in decreased liver ALT activity. (iv) DNA damage of peripheral blood lymphocytes was markedly inhibited by l-NAME or 7-NI treatment. (v) iNOS expression in brain and liver decreased by l-NAME or 7-NI. (vi) More marked improvement of the histopathological alterations induced by malathion in brain and liver was observed after 7-NI compared with l-NAME.In malathion intoxicated rats, the neuronal NOS inhibitor 7-NI and to much less extent l-NAME were able to protect the brain and liver tissue integrity along with improvement in oxidative stress parameters. The decrease in DNA damage of peripheral blood lymphocytes by NOS inhibitors also suggests the involvement of nitric oxide in this process.

Estimation of Postmortem Intervals by Some Biochemical Changes and DNA Degradation in Rat Brain and Skeletal Muscle Tissues

Accurate estimation of postmortem interval (PMI) is one of the most important and difficult issues in forensic medicine. After death, the tissues undergo autolysis and biomacromolecules degrade. The relationship of extent of DNA damage and certain components of the oxidant/antioxidant balance in brain and femoral muscle tissues of rats killed by cervical dislocation or drowning, with the post-mortem intervals was investigated and examined by making a relation with the histopathological finding in brain tissue. The results showed that the oxidant/antioxidant balance in brain and femoral muscle tissue was shift insignificant favour of the oxidants at 24 hrs postmortem and lasted tell 96 hours post-mortem toward the oxidant. The percentage of DNA fragmentation was detected increased parallel to significant increase of oxidant level from zero to 96 hrs post-mortem. The histopathological alterations in brain and muscle tissues of drowned or cervical dislocation were found to be in full accordance with biochemical finding and DNA fragmentation. Our results suggest that biochemical analysis, DNA fragmentation as well as histopathological examination of brain and muscle tissues provide an accurate estimation of post-mortem intervals.

Evaluation of Some Biochemical Parameters and Brain Oxidative Stress in Experimental Rats Exposed Chronically to Silver Nitrate and the Protective Role of Vitamin E and Selenium.

Due to undesirable hazardous interactions with biological systems, this investigation was undertaken to evaluate the effect of chronic exposure to silver on certain biochemical and some oxidative stress parameters with histopathological examination of brain, as well as the possible protective role of selenium and/or vitamin E as nutritional supplements. Thirty six male rats were divided into six groups of six each: the first group used as a control group. Group II given both vitamin E (400 mg/kg) of diet and selenium (Se) (1 mg/L) in their drinking water. Group III given silver as silver nitrate (AgNO3) (20 mg/L). Group IV given vitamin E and AgNO3. Group V given both AgNO3 and selenium. Group VI given AgNO3, vitamin E and Se. The animals were in the same exposure conditions for 3 months. According to the results which have been obtained; there was an increase in serum lactate dehydrogenase (LDH), lipase activities and cholesterol level, a decrease in serum total protein, calcium and alkaline phosphatase (ALP) activity in Ag-intoxicated rats. Moreover, the findings showed that Ag+ ions affected antioxidant defense system by decreasing superoxide dismutase (SOD) activity and increasing vitamin E concentration with a high level of malondialdehyde (MDA) in brain tissue. The histological examination also exhibited some nervous tissue alterations including hemorrhage and cytoplasm vacuolization. However, the co-administration of selenium and/or vitamin E ameliorated the biochemical parameters and restored the histological alterations. In conclusion, this study indicated that silver could cause harmful effects in animal body and these effects can be more toxic in high concentrations or prolonged time exposure to this metal. However, selenium and vitamin E act as powerful antioxidants which may exercise adverse effect against the toxicity of this metal.

Efficacy of intranasal administration of artesunate in experimental cerebral malaria.

BackgroundImproving management of patients suffering from cerebral malaria is needed to reduce the devastating mortality and morbidity of the disease in endemic areas. Intravenous artesunate is currently the first-line treatment, but the lack of material and skills in the field make it difficult to implement in endemic areas. Intranasal route provides a very easy and direct gateway to blood and brain to deliver medications, by-passing the brain blood barrier. Therefore, it could be helpful and suitable to administer artesunate in the context of cerebral malaria, especially in young children. In this study, intranasal administration of artesunate to rescue from cerebral malaria using a murine model was tested.MethodsCBA/J mice infected with Plasmodium berghei ANKA strain received artesunate (20 mg/kg) or a placebo solution intranasally, either on day 5, 6 or 7 post-infection, during a controlled, blinded, randomized trial. Primary endpoint was mortality on day 12 post-infection. Secondary endpoints were parasitaemia and clinical stage. Pharmacokinetics data following administration were collected in blood and brains of treated mice. Local toxicity was evaluated by histopathologic examination of brain and nasal sections in blinded manner.ResultsIntranasal administration of artesunate dramatically reduced the mortality rate (p < 0.001), preventing death in most cases. Parasitaemia loads decreased by 88.7% (61.8-100%) within 24 hours after administration. Symptoms of cerebral malaria were prevented or reversed. Dihydroartemisinin was detected in mice blood and brain within 15 minutes of intranasal administration. No direct nasal or brain toxicity was detected.ConclusionIntranasal delivery is an efficient route to timely and efficiently administer artesunate and therefore may contribute to decreasing malaria-related mortality.

Effects of Orlistat and herbal mixture extract on brain, testes functions and oxidative stress biomarkers in a rat model of high fat diet

This study was designed to assess the effectiveness of herbal mixture extracts of pumpkin seed oil, peanuts shell and Orlistat on brain, testes functions, oxidative stress biomarkers and histopathological changes in male albino rats administered high fat diet. Fifty male rats were divided into four groups: 1st administered normal diet, 2nd administered high fat diet, 3rd administered high fat diet with Orlistat and 4th administered high fat diet with herbal mix.A group of rats were fed with a standard control diet (1st control group was 12 rats for 22 weeks) and another group of rats were fed a diet containing 35% fat (2nd high fat diet) for 16 weeks. Then, this group of high fat diet was divided into 3 groups for the following 6 weeks: 1st group administered high fat diet only (13 rats), 2nd group administered high fat diet plus 2 mg/kg bw/day Orlistat (12 rats) and 3rd group administered high fat diet plus 5 mg/kg bw/day pumpkins and 2 mg/kg bw/day peanut shell extract (13 rats). Blood samples, brain and testes tissues were collected for biochemical assays and histopathological studies.High fat diet group showed a high significant increase (P < .001) in feed intake, body weight and body mass index. HFD showed a significant increasing in Nor Epinephrine, Dopamine, BCHE, Homocysteine and malondialdehyde contents in brain. In testes high fat diet increased malonaldehyde contents of testes. An improvement by the treatments with Orlistat and herbal mixture was observed. Histopathological examination of brain and testes sections of high fat diet rats supported the previous biochemical results.We concluded that the treatment with Orlistat and herbal mixture ameliorated the harmful effects of the high fat diet and reduce feed intake.

An evaluation of neurotoxic effect of metronidazole in rabbits

The present study was undertaken to assess the neurotoxic effect of metronidazole in rabbits .Eighteen rabbits were randomly divided into three equal groups ,first group was injected with metronidazole at the therapeutic dose 20 mg/kg.B.W. , second group was injected with metronidazole at double therapeutic dose where as the last group serve as a control .Each animal in all groups was administered intraperitoneally twice daily for (20) days . The evaluations markers have used in this study were monitering of clinical symptoms and determination of histopathological changes in brain and sciatic nerve. The careful observation of clinical signs ,reflexes (patellar ,cross extensor ,and papillary light) and certain responses (pupil size ,nystagmus and a menance response) in first and second group showed a remarkable nervous system dysfunction has improved by histopathological examination of brain and sciatic nerve .there were sever vacuolation in brain ,where the lesion was characterized by spongiform changes ,and degeneration of the nerve bundles in sciatic nerve were detected in rabbits treated with metronidazole at therapeutic dose ,where as there is degeneration and selective loss of parkinjii cells with sever congestion in brain as well as demylination and degeneration in sciatic nerve in rabbits treated with metronidazole at double therapeutic dose .This study revealed that metronidazole has a neurotoxic effect in rabbits (both centrally and peripherally ) with a severity depended on its dose and duration of administration.

Diagnosis of Clostridium Perfringens Intestinal Infections in Sheep and Goats

Clostridium perfringens produces enteric diseases, generically called enterotoxemias, in sheep, goats, and other animals. This microorganism can be a normal inhabitant of the intestine of most animal species, including humans, but when the intestinal environment is altered by sudden changes in diet or other factors, C. perfringens proliferates and produces potent toxins that act locally or are absorbed into the general circulation with usually devastating effects on the host. History, clinical signs, and gross postmortem findings are useful tools for establishing a presumptive diagnosis of clostridial enterotoxemia in sheep and goats. Definitive diagnosis requires laboratory confirmation. Isolation of some types of C. perfringens (e.g., B and C) can be of diagnostic value, but other types (e.g., A) are so commonly found in the intestine of normal animals that isolation is meaningless from a diagnostic point of view. The most accepted criterion in establishing a definitive diagnosis of enterotoxemia is detection of C. perfringens toxins in intestinal contents. Also, histopathological examination of brain is very useful for diagnosis of type D disease, as lesions produced by epsilon toxin in the brains of sheep and goats are pathognomonic for type D enterotoxemia. Ancillary tests, such as measuring urine glucose or observing Gram-stained smears of intestinal mucosa, can be used. However, although such tests have a presumptive diagnostic value when positive, they cannot be used to rule out a diagnosis of enterotoxemia when negative.

A 90-Day Toxicological Evaluation of 1,5-Anhydro-d-Fructose in Sprague–Dawley Rats

1,5-Anhydro-d-fructose (1,5-AF) is a novel monosaccharide produced by the action of α-1,4-glucan lyase (EC 4.2.2.13) on glycogen, starch, or related substrates such as maltose and maltosaccharides. 1,5-AF is of interest as a compound to be used as a food supplement because of its antioxidant, antimicrobial, and antidiabetic properties. This enforces the safety of 1,5-AF and therefore, in the current study, four groups of male and female Sprague–Dawley rats were provided with 1,5-AF in the drinking water (at 0 or 1.0 g/kg body weight daily) for a period of 90 days (n=10 in each group). All the animals survived, and no clinical signs of toxicity or alterations in hematological or clinical chemistry parameters were observed. Furthermore, organ weight and histopathological examination of brain, heart, urinary bladder, gastrointestinal tract, and pancreas were normal after 1,5-AF treatment. Moreover, there was no change in food consumption, water intake, or body weight gain in rats receiving 1,5-AF. In conclusion, administration of 1,5-AF did not induce any significant toxicological effects and, therefore, 1,5-AF seems safe to administer in vivo over a long period of time.

Dexamethasone Mediated Inhibition of Local IL-2 Immunotherapy is Dose Dependent in Experimental Brain Tumors

Local delivery of cytokines has been shown to have a potent anti-tumor activity against a wide range of malignant brain tumors. In this study, we examined the role of systemic immunosuppression using dexamethasone on the efficacy of local IL-2 immunotherapy in treating experimental murine CNS tumors. An endothelial cell line secreting hIL-2 (NTC-121) was injected intracranially in C57BL/6 mice (n = 10/ group) along with B16/F10 (wild type) melanoma cells. A separate set of animals also received daily injections of either 1 mg/k or 10 mg/kg of dexamethasone. Sixty percent of mice treated with IL-2 (P < 0.001 vs. control) vs. 55% (P < 0.005) of mice treated with IL-2 and 1 mg/kg of dexamethasone were long-term survivors (LTS) of > 120 days. There was no difference in survival between control animals that received only wild type cells or animals that were treated with IL-2 and 10 mg/kg of dexamethasone. Histopathological examination of brains from animals sacrificed at different times showed an accumulation of CD8 + T-cells around the site of the injected tumor only in the IL-2 group and the group that received 1 mg/kg of dexamethasone. These results suggest that while high doses of dexamethasone can completely inhibit the immune response observed with IL-2, lower and more likely therapeutic doses of dexamethasone do not inhibit local IL-2 immunotherapy.

Gene therapy for experimental brain tumors using a xenogenic cell line engineered to secrete hIL-2.

Local delivery of cytokines has been shown to have a potent anti-tumor activity against a wide range of malignant brain tumors. In this study, we examined the feasibility and efficacy of using a rat endothelial cell line (NTC-121) transfected with the human interleukin-2 (IL-2) gene in treating experimental murine CNS tumors. The NTC-121 cells were injected intracranially in C57BL/6 mice (N = 10/group) along with non-irradiated, non-transfected B16/F10 (wild type) melanoma cells. Sixty percent of mice treated with IL-2 (p < 0.001 vs. control) were long-term survivors (LTS) of > 120 days. Control animals that received only wild type cells had a median survival of 18 days (range 15-20). Histopathological examination of brains from animals sacrificed at different times showed no tumor growth in the non-irradiated NTC-121 group, moderate (1-2 mm) tumor growth in the irradiated group, and gross tumor invasion (>2 mm) and tissue necrosis in the control group. Moreover, animals treated with IL-2 showed an accumulation of CD8+ T cells around the site of the injected tumor. The use of a xenogenic cell line to deliver hIL-2 stimulates a strong immunologic cytotoxic anti-tumor response that leads to significant prolongation of survival in mice challenged with the B16/F10 intracranial melanoma tumor. Our findings demonstrate that the use of a xenogenic cell line can provide a potent vehicle for the delivery of gene therapy and may therefore represent a new approach for brain tumor therapy.