Necrosis Of Cortex Research Articles

Pancreatic islets as a SARS-CoV-2 target

Aim. The study is aimed at describing pancreatic islets as one of the SARS-CoV-2 targets.Materials and methods. The object of the study was the pancreas. The study involved histological staining.Results and discussion. The autopsy study revealed the signs typical of bilateral viral interstitial pneumonia. Histological examination revealed alveoli with disatelectasis, intra-alveolar edema, hyaline membranes in a part of alveoli. The pancreas histological examination showed hemorrhages, necrotic areas of the islets and detected the following DIC signs: small hyaline thrombi in the heart cavities and large vessels, petechial hemorrhages in the internal organs and adrenal glands, foci of adrenal cortex necrosis with perifocal infiltration (Waterhouse—Friderichsen syndrome); as well as signs of necronephrosis with fibrinoid areas of necrosis in the glomerular capillary network and perivascular lymphoid infiltrates.Conclusion. SARS-CoV-2 was revealed to target human pancreatic islets, where areas of necrosis developed.

Aluminium Induced Neurodegeneration in Rat Cerebrum in Presence of Ethanol Co-exposure

Introduction: Aluminium (AL) exposure leads to neurotoxicity and many problems in the body. AL role in Alzheimer's Disease (AD) is unknown and controversial to the scientists. According to World Health Organisation (WHO) provisional tolerable weekly intake of AL is 2 mg/kg body weight. Moderate intake of alcohol may favour body in coronary heart disease and diabetes mellitus, etc. Aluminium being cheaper along with increased consumption of alcohol, mixed with each other may induce neurotoxicity. Aim: The study was designed to identify the effects of AL in cerebrum of rats in presence of ethanol co-exposure. Materials and Methods: An experimental study was carried out at Dr. RP Government Medical College, Kangra and Government Medical College, Amritsar, India after due approval from the Institute Animal Ethics Committee. Thirty-two wistar rats were divided into one vehicle control and three experimental groups. Group I received the normal saline water as vehicle control group. Group II received AL chloride 4.2 mg/kg body weight as experimental group. Group III received ethanol 1 gm/kg body weight as experimental group. Group IV received both AL chloride 4.2 mg/kg body weight and ethanol 1 gm/kg body weight as experimental group. After treatment, brain cortex was processed for histopathological observation under microscope. Results: Cerebral cortex showed normal architecture of the brain with haematoxylin and eosin staining and cresyl violet staining and modified Bielchowsky silver staining in low and high magnification in vehicle control group. Experimental group treated with AL and ethanol separately showed reduction in the count of pyramidal cells with moderate neuronal degeneration with pyknotic nuclei. Vacuolar changes and pericellular spaces around the necrotic neurons were also seen. Combined AL and ethanol treated group showed acute neurodegeneration and necrosis of cortex indicating chromatolysis and loss of substances and Neurofibrillary Tangle (NFT) and plaque. Conclusion: It has been concluded that the ethanol induced the effects of AL on the cerebrum and plays a significant role in AD pathogenesis.

First report of Fusarium solani species complex as a causal agent of Erythrina variegata decline and death after gall formation by Quadrastichus erythrinae on Okinawa Island, Japan

The defoliation and mortality of Erythrina spp. are increasing on the southern islands of Japan as well as in Taiwan. Although infestation by the gall wasp Quadrastichus erythrinae has been accepted as the cause of Erythrina decline, its role in the death of hosts has never been investigated. We thus studied the cause of the decline, focusing on physiological changes and any contributions by microorganisms. From declining and defoliated trees, Fusarium sp. within F. solani species complex (FSSC) clade 3 was primarily detected, especially from discolored xylem and necrotic phloem that had an odor. This fungus belongs to the Ambrosia Fusarium clade, a group of symbionts of ambrosia beetles that includes the causal agent of Fusarium dieback on avocado. No specific fungi were detected from twigs and leaves with Q. erythrinae galls. According to histological observations, the internal symptoms of declining E. variegata are similar to those of sudden death syndrome in soybeans, which is caused by F. virguliforme, a member of FSSC clade 2. One of the isolates of the Fusarium sp. isolated from E. variegata induced wilt and necrosis of cortex and phloem in the seedlings after artificial inoculation, and the inoculated strain was reisolated. The present results demonstrated that the isolate was pathogenic to E. variegata and may be a causal agent of Erythrina decline.

Effect of panax notoginseng saponins on renal cortical tubule cell Bax in early stage after renal trauma in rats

Objective To measure the effect of panax notoginseng saponins (PNS) on renal cortical tubule cell apoptosis and apoptosis-related genes in early stage after renal trauma and to investigate the protective mechanism of PNS for renal trauma.Methods Seventy-eight Wistar rats were divided into trauma group (n =36),trauma + treatment group (treatment group,n =36),normal control group (control group,n =6) according to the random number table.In treatment group,rats received intraperitoneal administration of PNS (70 mg/kg).Instead,substitute of an equal dose of isotonic saline was used for the rats in trauma and normal control groups.Trauma and treatment groups were subdivided at 1,6,12,24,36 and 48 hours posttrauma,with 6 rats per group.The kidney specimens were extracted at each time point to detect Bax expression in the cortex with immunohistochemistry and in situ hybridization histochemistry.Moreover,the positive expression of Bax was compared among groups and its variation regularity with time were detected.Results In trauma group,mRNA transcription of pro-apoptosis gene Bax increased at 12 hours in the superficial cortex,but increased at 1 hour in deep cortex; protein expression of pro-apoptosis factor Bax showed no apparent reduction within 36 hours in the superficial cortex,but evident decrease within 12 hours in the deep cortex.In treatment group,mRNA transcription of pro-apoptosis gene Bax decreased immediately after treatment in the renal cortex and lasted until 48 h; protein expression of pro-apoptosis factor Bax showed unidirectional reduction until 48 h in the renal cortex.Conclusion PNS inhibits cell apoptosis by down-regulating the mRNA and protein expression of Bax. Key words: Wounds and injuries; Kidney; Apoptosis; Kidney cortex necrosis

A novel biomarker for acute kidney injury using TaqMan-based unmethylated DNA-specific polymerase chain reaction.

There has been increasing interest in the use of circulating DNA as biomarkers for various tissue injuries, cancers, and fetal conditions. DNA methylation is a well-characterized mechanism underlying the epigenetic regulation of gene expression, and many diagnostic tests based on DNA methylation patterns have been developed. We developed a novel TaqMan-based assay for the detection of acute kidney injury using a hypomethylated promoter region of Slc22a12, a urate transporter specifically expressed in proximal tubular cells. Bisulfite sequencing analysis confirmed that the CpG islands in the promoter region of mouse Slc22a12 were preferentially hypomethylated in the kidney cortex. TaqMan minor groove binder (MGB) probes reliably discriminated the DNA fragments corresponding to the unmethylated and methylated promoter regions of Slc22a12. Plasma levels of unmethylated DNA corresponding to the Slc22a12 promoter region were undetectable at baseline and were significantly elevated after acute kidney cortex necrosis. This study showed the usefulness of the TaqMan system in discriminating methylated and unmethylated DNA fragments, and the similar strategy can be applied for establishing biomarkers for various cellular injuries or pathological conditions.

Mitotane exhibits dual effects on steroidogenic enzymes gene transcription under basal and cAMP-stimulating microenvironments in NCI-H295 cells

Adrenocortical carcinoma (ACC) is an extremely rare and aggressive endocrine malignancy with a poor prognosis. The most common symptom of ACC is hypercortisolism (Cushing's syndrome), which has the highest mortality. Mitotane is used as a steroidogenesis inhibitor for Cushing's syndrome or as a chemical adrenalectomy drug for ACC. Mitotane induces adrenal cortex necrosis, mitochondrial membrane impairment, and irreversible binding to CYP proteins. In this study, we explored the molecular effect of mitotane on steroidogenesis in human adrenocortical cancer NCI-H295 cells. Mitotane (10–40μM) inhibited basal and cAMP-induced cortisol secretion but did not cause cell death. Mitotane exhibited an inhibitory effect on the basal expression of StAR and P450scc protein. Furthermore, 40μM of mitotane significantly diminished StAR, CYP11A1 and CYP21 mRNA expression. HSD3B2 and CYP17 seem to be insensitive to mitotane. The stimulatory effects of mitotane on CYP11B1 were more remarkable than its inhibitory effects. In contrast, the activation of cAMP signaling strongly elevated the expression of all these genes. Mitotane (40μM) almost completely neutralized this positive effect and returned 8-Br-cAMP-induced StAR, CYP11A1, CYP17 and CYP21 mRNA to control levels. After cAMP activation, mitotane did not change the levels of CYP11B1 mRNA. The present study demonstrates that mitotane can inhibit cortisol biosynthesis due to a non-specific interference with the gene transcription of steroidogenic enzymes under both basal and 8-Br-cAMP-activated conditions in NCI-H295 cells. We also identified that StAR and CYP11A1 key enzymes that participate in the rate-limiting step of steroidogenesis, were more sensitive to mitotane. In addition, the biphasic effect of mitotane on CYP11B1 was also elucidated.

A Case of Acute Kidney Cortex Necrosis Caused by Tranexamic-Acid

Kidney cortex necrosis is a relatively rare cause of acute kidney injury and is characterized by complete or partial destruction of the renal cortex, but sparing of the medulla. Tranexamic acid has antifibrinolytic activity and is used to reduce bleeding. We report a rare case of kidney cortex necrosis caused by tranexamic acid. A 49-year-old woman complained of coughing up blood-tinged sputum. She had a history of bronchiectasis and was treated with tranexamic acid for 3 days. Four days after admission, she developed anuria and azotemia. Computerized tomography showed enhancement of the renal medulla, but not the bilateral renal cortex. The patient was treated with hemodialysis, and has since been maintained on hemodialysis for 6 months. Due to the development of kidney cortex necrosis in patients treated with tranexamic acid, all its potential complications should be considered. (Korean J Med 2012;82:503-506)

Rhinocerebral and rhinopharyngeal conidiobolomycosis in sheep

The present study aimed to report the occurrence as well as the clinical, laboratorial, pathological and mycological findings of three outbreaks of rhinocerebral and rhinopharyngeal conidiobolomycosis in sheep from Rio Grande do Norte state, Brazil. A total of six sheep with clinical signs of conidiobolomycosis were evaluated, and information on history was obtained from ranchers. Clinical signs included depression, progressive emaciation, sero-sanguinolent nasal discharge, tachycardia, dyspnea, miosis and unilateral exophthalmia with increased ocular globe volume, corneal ulceration and nervous system signs. The main hematological alteration was neutrophilia. Serum biochemical evaluation revealed increased values for AST, GGT, creatinine, urea, and glucose, and decreased total proteins and albumin levels. Cerebrospinal fluid analysis showed the presence of fibrin reticules and pleocytosis. Upon necropsy, longitudinal sections of the head revealed the presence of a nodular mass with a friable consistency and a white-yellowish coloration. Microscopic findings included meningitis, cortex necrosis and encephalitis with the presence of eosinophilic Splendore-Hoeppli substance. Histopathology of the lungs revealed a Splendore-Hoeppli-like material and hyperplasia of alveolar and bronchiolar epithelium. Renal lesions were suggestive of amyloidosis.

A comparative study of protective mechanisms of glycine and L-arginine against cisplatin-induced nephrotoxicity in rat renal cortical slices

Amino acids exert nephroprotective effects in various forms of acute renal injury depending on their renal hemodynamic effects. The present study was designed to elucidate and compare the role of non hemodynamic mechanisms in protective actions afforded by glycine and L-arginine against cisplatin (CDDP)-induced nephrotoxicity using rat renal cortical slices (RCS). We have investigated the possible modulatory effect of glycine and L-arginine on oxidative stress and necrosis induced by CDDP as well as on CDDP uptake by kidney. After 4 h of incubation with 2 mM CDDP, nephrotoxicity was demonstrated by significant increased lactate dehydrogenase leakage, decreased ability of the slices to reduce 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, increased lipid peroxides and depleted reduced glutathione. Also, CDDP significantly inhibited pyruvate-stimulated gluconeogenesis. Histopathological examination of RCS confirmed the occurrence of tubular coagulative necrosis in cortex and corticomedullary regions. Preincubation of RCS with 1 mM glycine or L-arginine 1 h before CDDP addition significantly attenuated the oxidative stress and tubular necrotic effects of CDDP. L-Arginine showed greater antioxidant properties while glycine showed a greater antinecrotic effect. Moreover, the nephroprotective effect was mediated through lowering the platinum uptake by RCS. However, they could not counteract the inhibition of gluconeogenesis induced by CDDP. In conclusion, the present study sheds light on the mechanisms involved in glycine and L-arginine nephroprotection.

Cortical Laminar Necrosis in an Infant with Severe Traumatic Brain Injury

Cortical laminar necrosis appears as hyperinense lesions with a laminar pattern on T1 weighted magnetic resonance (MR) imaging, without signs of hemorrhage or calcification on T2 weighted MR imaging or computed tomography. It has been reported to be associated with hypoxia, metabolic disturbances, drugs, and infections. We present a 12 month-old male infant who suffered diffuse brain injuries following car accident and showed laminar necrosis of cortex.

Sickle Cell Anemia: Conclusions from a Forensic Case Report of a Young African Woman Who Died After Anesthesia

A 20-year old African woman underwent anesthesia for interruption of an unwanted pregnancy. As a consequence of the anesthesia, she went into coma because of an as yet unknown and untested homozygotic state of sickle cell anemia. Her vital functions were maintained for more than 1 year by intensive medicine, but she died finally in multiorgan failure and aspiration pneumonia. Because of the complications under anesthesia and the missing preanesthetic test for hemoglobinopathy, autopsy was conducted in the forensic medicine department and not in the department of pathology. The sickle cell disease was diagnosed by electrophoresis of the blood, by molecular detection of mutation in the hemoglobin gene, as well as by postmortem light and electron microscopy. Sickle cells were found in capillaries of brain, liver, lung, bone marrow, and spleen. Electrophoretic analysis revealed 80.2% HbS in addition to 3.2% HbA2 and 16.6% HbF, whereas no HbA0 could be detected in blood, confirming the homozygosity of sickle cell anemia. Because of sickle cell crisis, occluded blood vessels, and severe brain cortex necrosis, the patient died in spite of reanimation and intensive medicine. This case demonstrates that it is still important to realize the possibility of this disease and diagnostic obstacles even in regions where its manifestation is not endemic, as in Northern and Central Europe.

Mefenamate, an agent that fails to attenuate experimental cerebral infarction.

Blockade of nonselective cation channels is a potential therapeutic approach that has not been attempted in cerebral ischemia, in spite of the ability of these channels to allow cellular calcium influx into neurons. Fenamates are a class of molecules that block these channels, and many congeners are also anti-inflammatory and free radical scavenging. These three mechanisms may contribute to brain damage in ischemia. Pretreatment or posttreatment with mefenamate (30 mg/kg) was evaluated in a temperature-controlled rat transient focal ischemia model. Quantitative histopathology on 26 coronal sections allowed determination of tissue necrosis and tissue atrophy at one week survival. Neither pre- nor postischemic administration of a dose previously shown effective in preventing epileptic neuronal necrosis was found to reduce necrosis in cortex, nor in any subcortical structures. We conclude that nonselective cation channel blockade with mefenamate affords no neuroprotection in this model. Publication bias against negative studies exists in the literature, but we here report negative findings due to the multiple potentially positive actions of the drug. Closer examination of the effects of the molecule, however, reveals several potentially negative effects as well. We conclude there may be inherent weakness in pharmacologic monotherapy, even with molecules having protean potentially beneficial effects. This conclusion seems to have been borne out by the results of recent clinical trials.

Renal Artery Embolization with Diluted Hot Contrast Medium: An Experimental Study

To evaluate the safety and efficacy of diluted hot contrast medium to embolize the renal arteries in a canine model. Transcatheter embolization was performed in 15 dogs (five dogs in each phase: I, II, and control). The diluted hot contrast medium was heated to 90 degrees C--100 degrees C and 30--60 mL were injected into a renal artery of each dog in phase I (optimization studies) and II (efficacy studies). In the control group, balloon inflation was performed without injection of diluted hot contrast medium. The temperature measurement was performed on one dog in phase I by temperature probe. Follow-up angiography was performed immediately (n = 15), at 1 week (n = 9), at 1 month (n = 9), and after 3 months (n = 5). All dogs were killed and kidneys were removed for histologic examination. The procedure was performed successfully in all dogs. Follow-up angiography showed complete obstruction of the injected renal arteries in phases I and II. The microscopic findings showed acute full-thickness necrosis of the renal cortex and renal artery in phase I, and complete coagulative necrosis of the cortex, medulla, and intrarenal blood vessels in phase II. There were no histologic changes of renal veins, inferior vena cava (IVC), and aorta. There were nonspecific findings in the control group. This preliminary experimental study suggests that diluted hot contrast medium may be a safe agent for renal ablation without thrombus formation in the renal vein or IVC.

Graded hypotension and MCA occlusion duration: effect in transient focal ischemia.

The first 2 h of middle cerebral artery occlusion (MCAO) are likely critical in determining the final outcome in ischemic stroke. To study this early postischemic period, male Wistar rats (n = 161) were subjected to right MCAO with closely spaced step variations in both duration of MCAO and blood pressure (BP), using the intraluminal suture technique. Quantitative neuropathology was performed at 25 coronal planes of the brain after 1-week survival. Atrophy was measured as the difference between the two hemispheres and was added to cortical and striatal necrosis to obtain total tissue loss. Damage consistently increased monotonically with increasing duration of occlusion only when infarct size was expressed as percentage of the contralateral hemisphere, but not when expressed as mm3, because of variable tissue size. The results showed that already at 1 week, the quantity of tissue loss due to resorption and transsynaptic effects approached the quantity of geographically traceable necrosis in cortex and striatum. Minimum brain damage (5%) occurred after 60 min at a BP of 80 mm Hg, with almost no cortical necrosis. Damage was extremely sensitive to hypotension and MCAO duration. At a BP of 40 mm Hg, 60 min of MCAO produced 25% damage, accelerating every 20 min during the 2-h period studied. At BP 80 mm Hg, 120 min of MCAO produced the same damage as only 80 min of MCAO at BP 60 mm Hg. At 60-, 80-, 100-, and 120-min duration of MCAO, infarct size was significantly reduced with increasing BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Prechronic Inhalation Toxicity Studies of 2-Mercaptobenzimidazole (2-MBI)in F344/N Rats

2-Mercaptobenzimidazole (2-MBI), used in rubber processing, is a suspect carcinogen structurally related to ethylene thiourea. The inhalation toxicity of 2-MBI was evaluated in male and female F344/N rats exposed 6 hr/day, 5 days/week to respirable aerosols generated by spray atomization of aqueous suspensions of the 2-MBI powder and subsequent drying of the resulting aerosols. Twelve exposures at target concentrations of 0, 6.3, 12.5, 25.0, 50.0, or 100 mg/m3 of 2-MBI produced a dose-related reduction in body weight gains, thyroid follicular cell hyperplasia, adrenal cortex fatty change, and pituitary atrophy. Sub-chronic exposures were conducted at target concentrations of 0, 3.1, 6.2, 12.5, 25.0, and 50.0 mg/m3 of 2-MBI. Rats at ≥25 mg/m3 displayed hunched posture, hypoactivity, and reduced body weight gain, with compound related mortality at the highest exposure level. Anemia; increased SGPT, SGOT, alkaline phosphatase, sorbitol dehydrogenase, BUN, and cholesterol; and reduced free fatty acid were seen in rats at ≥25 mg/m3. Increased thyroid weight and thyroid follicular cell hyperplasia were noted in both sexes at ≥6.2 mg/m3, with reduced triiodothyronine and thyroxine levels in both sexes at > 12.5 mg/m3. Thyroid follicular cell hyperplasia was also seen in rats at 3.1 mg/m3. Thymus weights were significantly reduced in both sexes at all exposure levels with liver weight increases at ≥6.2 mg/m3. Exposure-related histopathologic changes included pituitary cytoplasmic vacuolization, adrenal cortex necrosis, lymphoid depletion, thymic atrophy, liver cell hypertrophy, renal mineralization and tubular atrophy, and hypocellularity of the bone marrow.

Prechronic inhalation toxicity studies of 2-mercaptobenzimidazole (2-MBI) in [formula omitted] rats

2-Mercaptobenzimidazole (2-MBI), used in rubber prucessing, is a suspect carcinogen structurally related to ethylene thiourea. The inhalation toxicity of 2-MBI was evaluated in male and female F344 N rats exposed 6 hr/day, 5 days/week to respirable aerosols generated by spray atomization of aqueous suspensions of the 2-MBI powder and subsequent drying of the resulting aerosols. Twelve exposures at target concentrations of 0, 6.3, 12.5, 25.0, 50.0, or 100 mg/m 3 of 2-MBI produced a dose-related reduction in body weight gains, thyroid follicular cell hyperplasia, adrenal cortex fatty change, and pituitary atrophy. Subchronic exposures were conducted at target concentrations of 0, 3.1, 6.2, 12.5, 25.0, and 50.0 mg/m 3 of 2-MBI. Rats at ≥25 mg/m 3 displayed hunched posture, hypoactivity, and reduced body weight gain, with compound related mortality at the highest exposure level. Anemia; increased SGPT, SGOT, alkaline phosphatase, sorbitol dehydrogenase, BUN, and cholesterol; and reduced free fatty acid were seen in rats at ≥25 mg/m 3. Increased thyroid weight and thyroid follicular cell hyperplasia were noted in both sexes at ≥6.2 mg/m 3, with reduced triiodothyronine and thyroxine levels in both sexes at ≥12.5 mg/m 3. Thyroid follicular cell hyperplasia was also seen in rats at 3.1 mg/m 3. Thymus weights were significantly reduced in both sexes at all exposure levels with liver weight increases at ≥6.2 mg/m 3. Exposure-related histopathologic changes included pituitary cytoplasmic vacuolization, adrenal cortex necrosis, lymphoid depletion, thymic atrophy, liver cell hypertrophy, renal mineralization and tubular atrophy, and hypocellularity of the bone marrow.

Nervous System Effects of Cardiac Arrest in Monkeys

Thirteen juvenile monkeys were taught two visual discrimination tasks. After 12 to 24 hours of food deprivation, ten underwent 14-minute episodes of cardiac arrest. Three served as controls. Five of the ten arrested animals survived and were tested in the discrimination box. All continued to perform color and pattern discrimination tasks with one to eight days' delay. All appeared neurologically intact, while brain pathologic examination after 11 to 64 days' survival showed either intact brains or injury restricted to nuclear structures in the brain stem, cerebellar Purkinje cells, and hippocampus. Five animals died 4 to 36 hours after they were resuscitated. Two required prolonged cardiac massage and, despite return of adequate cardiovascular function, died early. A third animal dislodged its arterial catheter and exsanguinated. The remaining two animals, who received infusions of glucose just prior to arrest, developed widespread fasciculations and myoclonic seizures. They became decerebrate and opisthotonic and were killed after 10 and 36 hours. Their brains showed mild edema and widespread necrosis of cortex and basal ganglia. Thus, food-deprived monkeys tolerate 14 minutes of circulatory arrest well and show minimal neurologic and pathologic changes, while administration of glucose just before arrest markedly augments the severity of brain injury and alters its distribution.

CORTICAL NECROSIS OF THE KIDNEY FOLLOWING TONSILLITIS

Bilateral, symmetric necrosis of the renal cortex is a rare condition which during the life of the patient often represents a rather difficult diagnostic problem. Kaufmann1described this condition as an extensive necrosis of the cortex of the kidney leading to rapid suppression of the excretion of urine and to death attended by uremic symptoms. Extensive confluent yellowish areas of cortical necrosis are found surrounded by deep red hemorrhagic rims and associated with extensive thromboses of the intrarenal arteries and veins. This lesion has been observed chiefly as a fatal complication of pregnancy, and 86 per cent of the cases reported in the literature fall in this group (Evans and Gilbert2). Other etiologic factors, such as tonsillitis, periarteritis nodosa, diphtheria, pulmonary tuberculosis, peritonitis and intravenous injections of camphor, must be considered as extremely rare; they are responsible for the small number of cases in which the condition has