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Nociceptive markers in mice have been identified in two distinct peptidergic and nonpeptidergic neurons in the dorsal root ganglion (DRG) and distributed in different laminae of the dorsal horn of the spinal cord. Recently, however, a study in humans showed a significant overlapping in these two populations. In this study, we investigated the distribution of various nociceptive markers in the lumbar DRG and spinal cord of the dromedary camel. Immunohistochemical data showed a remarkable percentage of total neurons in the DRG expressed IB4 binding (54.5%), calcitonin gene-related peptide (CGRP; 49.5%), transient receptor potential vanilloid 1 (TRPV1; 48.2%), and nitric oxide synthase (NOS; 30.6%). The co-localization data showed that 89.6% and 74.0% of CGRP- and TRPV1-labeled neurons, respectively, were IB4 positive. In addition, 61.6% and 84.2% of TRPV1- and NOS-immunoreactive neurons, respectively, were also co-localized with CGRP. The distribution of IB4, CGRP, TRPV1, substance P, and NOS immunoreactivities in the spinal cord were observed in lamina I and outer lamina II (IIo). Quantitative data showed that 82.4% of IB4-positive nerve terminals in laminae I and IIo were co-localized with CGRP, and 86.0% of CGRP-labeled terminals were co-localized with IB4. Similarly, 85.1% of NOS-labeled nerve terminals were co-localized with CGRP. No neuropeptide Y (NPY) or cholecystokinin (CCK) immunoreactivities were detected in the DRG, and no co-localization between IB4, NPY, and CCK were observed in the spinal cord. Our results demonstrate marked convergence of nociceptive markers in the primary afferent neurons in camels, which is similar to humans rather than the mouse. The data also emphasizes the importance of interspecies differences when selecting ideal animal models for studying nociception and treating chronic pain.

Doxorubicin (DOXO) is a potent chemotherapeutic drug that is used in the treatment of a large number of cancers. Despite its important chemotherapeutic characteristics, its usage is limited because of the serious side effects; the most noticeable is cardiotoxicity which can manifest acutely or years after completion of treatment leading to left ventricular dysfunction, dilated cardiomyopathy and heart failure. Nootkatone (NK) is a recognized bioactive compound isolated from the heartwood of Cupressus nootkatensis and has been reported to have antiseptic, antioxidant, and anti-allergic activities.Male C57B6/J mice were used for mice model of DOXO-cardiac toxicity. Mice were given either DOXO or NK or DOXO+NK or vehicle (normal saline) after which the mice again had free access to food and water. Heart and plasma samples were collected 5 days after DOXO administration and were used for immunohistochemistry, electron microscopy and enzyme linked immunosorbent assay (ELISA).There were significant reduction in inflammatory markers in hearts of DOXO-NK- treated mice when compared with DOXO-treated mice. Moreover, there were significant increase in antioxidant proteins and reduction of oxidative stress in hearts of DOXO-NK-treated mice when compared with DOXO-treated mice. There was a significant reduction in myocardial damage as shown by significant reduction of troponin I in DOXO-NK- treated mice when compared with DOXO-treated mice.Nootkatone improves DOXO-induced myocardial injury through modulation of NF-κB signals and reduction of oxidative stress.

The downregulation of cannabinoid type-2 receptors (CB2R) have been reported in numerous diseases including cardiovascular diseases (CVDs). The activation of CB2R has recently emerged as an important therapeutic target to mitigate myocardial injury. We examined whether CB2R activation can protect against isoproterenol (ISO)-induced myocardial injury (MI) in rats. In the present study, we investigated the cardioprotective effect of β-caryophyllene (BCP), a naturally occurring dietary cannabinoid in rat model of MI. Rats were pre- and co-treated with BCP (50 mg/kg, orally) twice daily for 10 days along with subcutaneous injection of ISO (85 mg/kg) at an interval of 24 h for two days (9th and 10th days). AM630 (1 mg/kg), a CB2 receptor antagonist, was injected intraperitoneal as a pharmacological challenge prior to BCP treatment to reveal CB2R-mediated cardioprotective mechanisms of BCP. Desensitization of beta-adrenergic receptor (β-AR) signaling, receptor phosphorylation and recruitment of adapter β-arrestins were observed in ISO-induced MI in rats. ISO injections caused impaired cardiac function, elevated the levels of serum cardiac marker enzymes, and enhanced oxidative stress markers along with altered PI3K/Akt and NrF2/Keap1/HO-1 signaling pathways. ISO also promoted lysosomal dysfunction along with activation of NLRP3 inflammasomes and TLR4-NFκB/MAPK signaling and triggered rise in proinflammatory cytokines. There was a concomitant mitochondrial dysfunction followed by the activation of endoplasmic reticulum (ER) stress-mediated Hippo signaling and intrinsic pathway of apoptosis as well as altered autophagic flux/mTOR signaling in ISO-induced MI. Furthermore, ISO also triggered dyslipidemia evidenced by altered lipids, lipoproteins and lipid marker enzymes along with ionic homeostasis malfunction. However, treatment with BCP resulted in significant protective effects on all biochemical and molecular parameters analyzed. The cardioprotective effects were further strengthened by preservation of cardiomyocytes and cell organelles as observed in histopathological and ultrastructural studies. Interestingly, treatment with AM630, a CB2R antagonist was observed to abrogate the protective effects of BCP on the biochemical and molecular parameters except hyperlipidemia and ionic homeostasis in ISO-induced MI in rats. The present study findings demonstrate that BCP possess the potential to protect myocardium against ISO-induced MI in a CB2-dependent and independent manner.

Doxorubicin (DOXO) is an effective drug that is used in the treatment of a large number of cancers. Regardless of its important chemotherapeutic characteristics, its usage is restricted because of its serious side effects; the most obvious is cardiotoxicity, which can manifest acutely or years after completion of treatment, leading to left ventricular dysfunction, dilated cardiomyopathy, and heart failure. Galectin 3 (Gal-3) is a beta galactoside binding lectin that has different roles in normal and pathophysiological conditions. Gal-3 was found to be upregulated in animal models, correlating with heart failure, atherosclerosis, and myocardial infarction. Male C57B6/J and B6.Cg-Lgals3 /J Gal-3 knockout (KO) mice were used for a mouse model of acute DOXO-induced cardiotoxicity. Mice were given DOXO or vehicle (normal saline), after which the mice again had free access to food and water. Heart and plasma samples were collected 5 days after DOXO administration and were used for tissue processing, staining, electron microscopy, and enzyme-linked immunosorbent assay (ELISA). There was a significant increase in the heart concentration of Gal-3 in Gal-3 wild type DOXO-treated mice when compared with the sham control. There were significantly higher concentrations of heart cleaved caspase-3, plasma troponin I, plasma lactate dehydrogenase, and plasma creatine kinase in Gal-3 KO DOXO-treated mice than in Gal-3 wild type DOXO-treated mice. Moreover, there were significantly higher heart antioxidant proteins and lower oxidative stress in Gal-3 wild type DOXO-treated mice than in Gal-3 KO DOXO-treated mice. In conclusion, Gal-3 can affect the redox pathways and regulate cell survival and death of the myocardium following acute DOXO injury.

Background/aims Galectin 3 (GAL-3) is a beta galactoside binding lectin that has different roles in normal and pathophysiological conditions. GAL-3 has been associated with heart failure and was linked to increased risk of death in a number of studies. GAL-3 was found to be up regulated in animal models of heart failure as well as myocardial infarction (MI). The objective of his study is to test if high GAL-3 after myocardial infarction has a protective role on the heart through its anti-apoptotic and anti-necrotic functions. Methods Male C57B6/J mice and GAL-3 knockout (KO) mice were used for permanent ligation of the left anterior descending artery of the heart to create infarction in the anterior myocardium. Heart and plasma samples were collected 24 hours after the induction of MI and were used for immunohistochemistry, Tunnel procedure, electron microscopy and enzyme linked immunosorbent assay (ELISA). Results Our results show that the significant increase in GAL-3 levels in the left ventricle at 24-hour following MI is associated with significant lower levels of pro-apoptotic proteins; cytochrome c, Bax, annexin V, cleaved caspase-3 and a higher levels of anti-apoptotic protein Bcl2 in GAL-3 wild MI group than GAL-3 KO group. We also have identified the anti-apoptotic activity of GAL-3 is mediated through a significant increase in Akt-1, NF kappa-B and beta- catenin proteins. In addition, we have identified the antiapoptotic activity is mediated through a significant lower levels of cathepsin-D protein. Conclusion We conclude that the increased levels of GAL-3 at 24-hour following MI regulate antiapoptotic mechanisms in the myocardium that will shape the future course of the disease. We also identified that the anti-apoptotic mechanisms are likely mediated through interaction of GAL-3 with Akt-1, NF kappa-B, beta- catenin and cathepsin D proteins.

Emerging evidence demonstrates that NLRP3 inflammasome activation, lysosomal dysfunction, and impaired autophagic flux play a crucial role in the pathophysiology of myocardial infarction (MI). Therapeutic strategies targeting NLRP3 activation, lysosomal enzyme release and correcting autophagy have shown beneficial effects in suppressing early inflammatory responses in cardiovascular diseases. Thus, the agents, which inhibit NLRP3 activation and correct lysosome dysfunction and impaired autophagic flux, can be potential drugs for MI. The present study evaluated the effects and elucidated the NLRP3 inflammasome mediated mechanism of α-bisabolol, a dietary sesquiterpene alcohol in a rat model of isoproterenol (ISO)-induced MI. In the present study, male albino Wistar rats were pre- and co-treated with intraperitoneal injection of α-bisabolol (25 mg kg-1) daily for 10 days along with the subcutaneous injection of ISO (85 mg kg-1) at an interval of 24 h for two days (9th and 10th day). ISO injections induced MI as evidenced by the elevated cardiac marker enzyme in serum and altered oxidative stress markers in the total heart and lysosomal fractions. ISO also caused activation of NLRP3 inflammasomes mediating TLR4-NFκB/MAPK signaling pathways and lysosomal dysfunction along with induction and release of proinflammatory cytokines. Interestingly, treatment with α-bisabolol favorably corrected the morphological, histopathological, ultrastructural, biochemical and molecular abnormalities induced by ISO-induced MI in rats. Furthermore, the ultrastructural studies also confirmed the improvement in the autophagic mechanism. The findings of the present study clearly demonstrate that α-bisabolol attenuates oxidative stress and inflammation by inhibiting NLRP3 inflammasome activation and TLR4-NFκB/MAPK signaling pathways along with correcting lysosomal dysfunction and impaired autophagic flux. The underlying pharmacological and molecular mechanism of cardioprotection was attributed to its antioxidant, free radical scavenging and anti-inflammatory properties.

With advent of nanotechnology, silver nanoparticles, AgNPs owing majorly to their antibacterial properties, are used widely in food industry and biomedical applications implying human exposure by various routes including inhalation. Several reports have suggested AgNPs induced pathophysiological effects in a cardiovascular system. However, cardiovascular diseases such as hypertension may interfere with AgNPs-induced response, yet majority of them are understudied. The aim of this work was to evaluate the thrombotic complications in response to polyethylene glycol- (PEG-) coated AgNPs using an experimental hypertensive (HT) mouse model. Saline (control) or PEG-AgNPs (0.5 mg/kg) were intratracheally (i.t.) instilled four times, i.e., on days 7, 14, 21, and 28 post-angiotensin II-induced HT, or vehicle (saline) infusion. On day 29, various parameters were assessed including thrombosis in pial arterioles and venules, platelet aggregation in whole blood in vitro, plasma markers of coagulation, and fibrinolysis and systemic oxidative stress. Pulmonary exposure to PEG-AgNPs in HT mice induced an aggravation of in vivo thrombosis in pial arterioles and venules compared to normotensive (NT) mice exposed to PEG-AgNPs or HT mice given saline. The prothrombin time, activated partial thromboplastin time, and platelet aggregation in vitro were exacerbated after exposure to PEG-AgNPs in HT mice compared with either NT mice exposed to nanoparticles or HT mice exposed to saline. Elevated concentrations of fibrinogen, plasminogen activator inhibitor-1, and von Willebrand factor were seen after the exposure to PEG-AgNPs in HT mice compared with either PEG-AgNPs exposed NT mice or HT mice given with saline. Likewise, the plasma levels of superoxide dismutase and nitric oxide were augmented by PEG-AgNPs in HT mice compared with either NT mice exposed to nanoparticles or HT mice exposed to saline. Collectively, these results demonstrate that PEG-AgNPs can potentially exacerbate the in vivo and in vitro procoagulatory and oxidative stress effect in HT mice and suggest that population with hypertension are at higher risk of the toxicity of PEG-AgNPs.

Type 1 diabetes mellitus (DM1) is linked to a decrease in bone strength. Bone strength entails both bone mineral density and bone quality. Limited data are available regarding diabetes-induced microdamage, which can severely influence bone quality. This study has investigated bone microdamage as a measure of bone quality in an animal model of DM1. Microdamage in the neck of the femur was labelled in vivo using multiple fluorochromes at 4, 12 and 24 weeks after the onset of DM1. Microcracks were quantified and their morphology analyzed using microscopy techniques. The mean length of microcracks at 24 weeks, and crack numerical and surface densities were significantly higher (p in vivo at different time points of DM1. DM1is associated with microcracks from the early stage, however bone microstructure shows toughening mechanisms that arrest their growth but disease progression further deteriorates bone quality resulting in longer microcracks which may increase fracture risk.

Background Dehydration has deleterious effects in many species, but camels tolerate long periods of water deprivation without serious health compromise. The kidney plays crucial role in water conservation, however, some reports point to elevated kidney function tests in dehydrated camels. In this work, we investigated the effects of dehydration and rehydration on kidney cortex and medulla with respect to pro-inflammatory markers, oxidative stress and apoptosis along with corresponding gene expression. Results The cytokines IL-1β and IL-18 levels were significantly elevated in the kidney cortex of dehydrated camel, possibly expressed by tubular epithelium, podocytes and/or mesangial cells. Elevation of IL-18 persisted after rehydration. Dehydration induced oxidative stress in kidney cortex evident by significant increases in MDA and GSH, but significant decreases in SOD and CAT. In the medulla, CAT decreased significantly, but MDA, GSH and SOD levels were not affected. Rehydration abolished the oxidative stress. In parallel with the increased levels of MDA, we observed increased levels of PTGS1 mRNA, in MDA synthesis pathway. GCLC mRNA expression level, involved in GSH synthesis, was upregulated in kidney cortex by rehydration. However, both SOD1 and SOD3 mRNA levels dropped, in parallel with SOD activity, in the cortex by dehydration. There were significant increases in caspases 3 and 9, p53 and PARP1, indicating apoptosis was triggered by intrinsic pathway. Expression of BCL2l1 mRNA levels, encoding for BCL-xL, was down regulated by dehydration in cortex. CASP3 expression level increased significantly in medulla by dehydration and continued after rehydration whereas TP53 expression increased in cortex by rehydration. Changes in caspase 8 and TNF-α were negligible to instigate extrinsic apoptotic trail. Generally, apoptotic markers were extremely variable after rehydration indicating that animals did not fully recover within three days. Conclusions Dehydration causes oxidative stress in kidney cortex and apoptosis in cortex and medulla. Kidney cortex and medulla were not homogeneous in all parameters investigated indicating different response to dehydration/rehydration. Some changes in tested parameters directly correlate with alteration in steady-state mRNA levels.

Mitochondrial dysfunction plays crucial role in the pathologenesis of myocardial infarction (MI). The present study evaluated the protective effect of α-bisabolol against isoproterenol (ISO)-induced mitochondrial dysfunction and apoptosis in rats. Male albino Wistar rats were pre- and co-treated with intraperitoneal injection of α-bisabolol (25 mg/kg body weight) daily for 10 days. To induce experimental MI, ISO (85 mg/kg body weight) was injected subcutaneously to the rats at an interval of 24 h for 2 days (9th and 10th day). ISO-induced MI was indicated by the decreased activities of heart creatine kinase and lactate dehydrogenase in rats. ISO administration also enhanced the concentrations of heart mitochondrial lipid peroxidation products and decreased the activities/concentrations of mitochondrial antioxidants, Kreb’s cycle dehydrogenases and mitochondrial electron transport chain complexes I, II + III and IV in rats. Furthermore, ISO triggers calcium overload and ATP depletion in the rat’s heart mitochondria followed by the mitochondrial cytochrome-C release and the activation of intrinsic pathway of apoptosis by upregulating the myocardial pro-apoptotic Bax, P53, APAF-1, active caspase-3, active caspase-9 and down regulating the expressions of anti-apoptotic Bcl-2. α-Bisabolol pre and co-treatment showed considerable protective effects on all the biochemical and molecular parameters studied. Transmission electron microscopic study and mitochondrial swelling assay confirmed our biochemical and molecular findings. The in vitro study on hydroxyl radical also revealed the potent free radical scavenging activity of α-bisabolol. Thus, α-bisabolol attenuates mitochondrial dysfunction and intrinsic pathway of apoptosis in ISO-induced myocardial infarcted rats.

The effects of early (5-day) onset of diabetes mellitus (DM) on retina ultrastructure and cellular bioenergetics were examined. The retinas of streptozotocin-induced diabetic rats were compared to those of non-diabetic rats using light and transmission electron microscopy. Tissue localization of glucagon-like-peptide-1 (GLP-1), exendin-4 (EXE-4), and catalase (CAT) in non-diabetic and diabetic rat retinas was conducted using immunohistochemistry, while the retinal and plasma concentration of GLP-1, EXE-4, and CAT were measured with ELISA. Lipid profiles and kidney and liver function markers were measured from the blood of non-diabetic and diabetic rats with an automated biochemical analyzer. Oxygen consumption was monitored using a phosphorescence analyzer, and the adenosine triphosphate (ATP) level was determined using the Enliten ATP assay kit. Blood glucose and cholesterol levels were significantly higher in diabetic rats compared to control. The number of degenerated photoreceptor cells was significantly higher in the diabetic rat retina. Tissue levels of EXE-4, GLP-1 and CAT were significantly (p = 0.002) higher in diabetic rat retina compared to non-diabetic controls. Retinal cellular respiration was 50% higher (p = 0.004) in diabetic (0.53 ± 0.16 µM O2 min−1 mg−1, n = 10) than in non-diabetic rats (0.35 ± 0.07 µM O2 min−1 mg−1, n = 11). Retinal cellular ATP was 76% higher (p = 0.077) in diabetic (205 ± 113 pmol mg−1, n = 10) than in non-diabetic rats (116 ± 99 pmol mg−1, n = 12). Thus, acute (5-day) or early onslaught of diabetes-induced hyperglycemia increased incretins and antioxidant levels and oxidative phosphorylation. All of these events could transiently preserve retinal function during the early phase of the progression of diabetes.

The feline immunodeficiency virus (FIV) full-length Pr50Gag precursor is a key player in the assembly of new viral particles. It is also a critical component of the efficient selection and packaging of two copies of genomic RNA (gRNA) into the newly formed virus particles from a wide pool of cellular and spliced viral RNA. To understand the molecular mechanisms involved during FIV gRNA packaging, we expressed the His6-tagged and untagged recombinant FIV Pr50Gag protein both in eukaryotic and prokaryotic cells. The recombinant Pr50Gag-His6-tag fusion protein was purified from soluble fractions of prokaryotic cultures using immobilized metal affinity chromatography (IMAC). This purified protein was able to assemble in vitro into virus-like particles (VLPs), indicating that it preserved its ability to oligomerize/multimerize. Furthermore, VLPs formed in eukaryotic cells by the FIV full-length Pr50Gag both in the presence and absence of His6-tag could package FIV sub-genomic RNA to similar levels, suggesting that the biological activity of the recombinant full-length Pr50Gag fusion protein was retained in the presence of His6-tag at the carboxy terminus. Successful expression and purification of a biologically active, recombinant full-length Pr50Gag-His6-tag fusion protein will allow study of the intricate RNA-protein interactions involved during FIV gRNA encapsidation.

The cannabinoid type 2 receptor (CB

Epstein-Barr virus-encoded RNAs (EBER1 and EBER2) are two highly abundant, non-protein coding RNAs consistently expressed in all EBV infected cells, but their function remains poorly understood. Conventional in situ hybridization studies have indicated that these RNAs are present exclusively in the nucleus. We have recently demonstrated that EBERs can be excreted from infected cells via exosomes. However, the details of the steps involved in their excretion remain unknown. In this study, we aimed to directly track the journey of EBERs from the nucleus to the excretory exosomes of EBV immortalized B-lymphocytes. Using a combination of molecular and novel immuno-gold labelled electron microscopy (EM) based techniques, we demonstrate the presence of EBERs, not only in the nucleus, but also in the cytoplasm of EBV infected B cell lines. EBERs were also seen in exosomes shed from infected cells along with the EBER binding protein La. Our results show, for the first time, that at least a proportion of EBERs are transported from the nucleus to the cytoplasm where they appear to be loaded into multi-vesicular bodies for eventual excretion via exosomes.

Inflammation is a crucial defense mechanism that protects the body from the devastating effects of invading pathogens. However, an unrestrained inflammatory reaction may result in systemic manifestations with dire consequences to the host. The extent of activation of the inflammatory response is tightly regulated through immunological and neural pathways. Previously, we demonstrated that cholinergic stimulation confers enhanced protection in experimental animals orally infected with virulent Salmonella enterica serovar Typhimurium. In this study, we investigated the mechanism by which this enhanced protection takes place. Cholinergic stimulation was induced by a 3-week pretreatment with paraoxon, a highly specific acetylcholinesterase inhibitor. This treatment enhanced host survival following oral-route infection and this correlated with significantly reduced bacterial load in systemic target organs. Enhanced protection was not due to increased gut motility or rapid bacterial clearance from the gastrointestinal tract. Moreover, protection against bacterial infection was not evident when the animals were infected systemically, suggesting that acetylcholine-mediated protective effect was mostly confined to the gut mucosal tissue. In vivo imaging demonstrated a more localized infection and delay in bacterial dissemination into systemic organs in mice pre-treated with paraoxon. Morphological analysis of the small intestine (ileum) showed that acetylcholinesterase inhibition induced the degranulation of goblet cells and Paneth cells, two specialized secretory cells involved in innate immunity. Our findings demonstrate a crucial pathway between neural and immune systems that acts at the mucosal interface to protect the host against oral pathogens.

Nociceptin (NC), also known as Orphanin FQ, is a brain peptide involved in the regulation of pain, but its role in the endocrine pancreas is poorly understood. The present study examines the pattern of distribution of NC and its effect on insulin and glucagon secretion after the onset of diabetes mellitus (DM). Male Wistar rats weighing 150–200 g were made diabetic with streptozotocin (60 mg/kg body weight, intraperitoneally). Four weeks after the induction of DM, pancreatic tissues were retrieved and processed for immunofluorescence, immunoelectron microscopy, and insulin and glucagon secretion. Isolated islets from non-diabetic and diabetic rats were used to determine the effect of NC on insulin release. NC was discerned in islet cells of non-diabetic control and diabetic rat pancreata. NC co-localized only with insulin in pancreatic beta cells. NC did not co-localize with either glucagon or somatostatin or pancreatic polypeptide. The number of NC-positive cells was markedly (p

OBJECTIVES Nociceptin has been reported to play an important role in the regulation of pancreatic exocrine secretion. Most of the studies performed on nociceptin are mainly physiological rather than morphological in nature. The present study investigated the pattern of distribution of nociceptin in the endocrine pancreas of normal and diabetic rats. METHODS Immunohistochemistry, immunofluorescence, Western blot, and double-labeled immunoelectron microscopy were used in this study. Diabetes was induced using streptozotocin (60 mg/kg body weight). RESULTS Nociceptin-immunoreactive cells were observed in the central and peripheral regions of the islets of both normal and diabetic rat pancreas. The number of nociceptin-positive cells was significantly (P < 0.05) lower in the islet of diabetic rats compared with the control. Immunofluorescence study showed that nociceptin colocalizes with insulin in pancreatic β-cells. The degree of colocalization of nociceptin with insulin was severely deranged after the onset of diabetes. Moreover, immunogold particles conjugated with either nociceptin or insulin were observed on the granules of pancreatic β-cell. The number of nociceptin-labeled colloidal gold particles was significantly lower after the onset of diabetes. CONCLUSIONS Nociceptin is present in pancreatic islets cells and colocalizes with insulin. Nociceptin may have a physiological role in the metabolism of insulin.

The present study investigates the cardioprotective effect of β-caryophyllene against doxorubicin-induced acute cardiotoxicity in rats. Doxorubicin (12.5 mg/kg) and β-caryophyllene (25, 50 or 100 mg/kg) were administered intraperitoneally to male albino Wistar rats. Doxorubicin-treated rats showed elevated levels of creatine kinase-MB in serum and oxidative stress in the myocardium as evidenced by decreased superoxide dismutase, catalase and glutathione with a concomitant rise in malondialdehyde levels. Doxorubicin also induced pro-inflammatory cytokines release following activation of the nuclear factor kappa-B and elevated expressions of inducible nitric oxide synthase and cyclooxygenase-2 in the myocardium. Additionally, doxorubicin also increased expression of γ-H2AX, a marker of DNA damage as well as increased expression of proapoptotic (Bax, p53, and active caspase-3) proteins along with the decreased expression of anti-apoptotic protein, Bcl2 in the myocardium. The histological and ultrastructural studies further revealed edema, inflammation and structural degeneration of cardiomyocytes following doxorubicin injection. However, treatment with β-caryophyllene showed significant cardioprotective effects as evidenced by favorable improvement of biochemical and molecular parameters along with remarkable preservation of cardiomyocytes in histological and ultrastructural studies. Results of the present study demonstrate that β-caryophyllene has potential to protect heart against doxorubicin-induced acute cardiotoxicity in rats. Moreover, the antioxidant and free radical scavenging properties of β-caryophyllene was confirmed by in vitro assays. Provided the anticancer and chemosensitizing properties of β-caryophyllene, the cardioprotective effects of β-caryophyllene are suggestive of its multiple properties that provides an additional basis of its possible therapeutic application in chemotherapy-associated cardiotoxicity.

Nociceptinergic system has become an important target for drug development since the identification of the "orphan", opioid-like-1 receptor and the isolation of its endogenous agonist nociceptin. Involvement of nociceptinergic system has been verified in a wide range of pathophysiological processes. A large number of nociceptinergic agonists and antagonists with peptide and non-peptide structures have been developed. Several non-peptide nociceptinergic antagonists have recently shown effective on different animal models of parkinsonism. Neuropharmacological background for antiparkinsonian effect of nociceptinergic antagonists, experimental models with high predictive value, nociceptinergic antagonists shown to have potential effect in Parkinson's disease are summarized. Medicinal chemistry data (logP and TPSA) of the NOP receptor antagonists which are found to be effective in animal models of Parkinson's disease are provided.

Lead (Pb) is known to cause abnormal function of several systems including the male reproductive system, where it has been shown to reduce sperm count. In order to examine the morphological basis of the reduction in sperm count and a possible effect of vitamin E, lead acetate (1 mg/kg body weight) was given to control and vitamin E-treated mice daily, intraperitoneally for 3 weeks. The testis and body of epididymis of the mice were subjected to electron microscopy study. Pb caused degenerative changes in spermatids inducing vacuolization and a reduction in the number of cytoplasmic organelles in Leydig cells. Pb also destroyed the stereocilia of epididymal epithelium. The addition of vitamin E ameliorated the severity of these morphological changes. In conclusion, Pb-induced reduction in sperm count may be due to changes in the ultrastructure of spermatids, epididymal epithelia and Leydig cells. These changes can be reduced by vitamin E.

Organophosphorus compounds (OPCs) have a wide range of applications, from agriculture to warfare. Exposure to these brings forward a varied kind of health issues globally. Terbufos is one of the leading OPCs used worldwide. The present study investigates the cardiac effect of no observable dose of a metabolite of terbufos, terbufos-sulfone (TS), under non-diabetic and streptozotocin-induced diabetic condition. One hundred nanomoles per rat (1/20 of LD50) was administered intraperitoneally to adult male Wister rats daily for fifteen days. The left ventricle was collected for ultrastructural changes by transmission electron microscopy. The blood samples were collected for biochemical tests including RBC acetylcholinesterase, creatinine kinase (CK), lactate dehydrogenase (LDH), cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, ALT, AST, and GGT. The study revealed about 10 % inhibition of RBC-AChE in two weeks of TS treatment in non-diabetic rats whereas RBC-AChE activity was significantly decreased in diabetic TS treated rats. CK, LDH, and triglycerides were significantly higher in diabetic TS treated rats. Electron microscopy of the heart showed derangement and lesions of the mitochondria of cardiomyocytes in the TS treated groups. The present study concludes that a non-lethal dose of TS causes cardiac lesions which exacerbate under diabetic condition. Biochemical tests confirmed the ultrastructural changes. It is concluded that a non-lethal dose of TS may be a risk factor for a cardiovascular disease, which may be fatal under diabetic condition.

Background Ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) are being developed for several biomedical applications including drug delivery and imaging. However, little is known about their possible adverse effects on thrombosis and cardiac oxidative and DNA damage. Methods Presently, we investigated the acute (1 h) effect of intravenously (i.v.) administered USPIO in mice (0.4, 2 and 10 μg/kg). Diesel exhaust particles (DEP; 400 μg/kg) were used as positive control. Results USPIO induced a prothrombotic effect in pial arterioles and venules in vivo and increased the plasma plasminogen activator inhibitor-1 (PAI-1). Both thrombogenicity and PAI-1 concentration were increased by DEP. The direct addition of USPIO (0.008, 0.04 and 0.2 μg/ml) to untreated mouse blood dose-dependently induced in vitro platelet aggregation. USPIO caused a shortening of activated partial thromboplastin time (aPTT) and prothrombin time (PT). Similarly, DEP administration (1 μg/ml) triggered platelet aggregation in vitro in whole blood. DEP also reduced PT and aPTT. The plasma levels of creatine phosphokinase-MB isoenzyme (CK-MB), lactate dehydrogenase (LDH) and troponin-I were increased by USPIO. DEP induced a significant increase of CK-MB, LDH and troponin I levels in plasma. The cardiac levels of markers of oxidative stress including lipid peroxidation, reactive oxygen species and superoxide dismutase activity were increased by USPIO. Moreover, USPIO caused DNA damage in the heart. Likewise, DEP increased the markers of oxidative stress and induced DNA damage in the heart. Conclusion We conclude that acute i.v. administration of USPIO caused thrombosis and cardiac oxidative stress and DNA damage. These findings provide novel insight into the pathophysiological effects of USPIO on cardiovascular homeostasis, and highlight the need for a thorough evaluation of their toxicity.

A novel in vitro system was developed to investigate the effects of two forms of calcined mesoporous silica particles (MCM41-cal and SBA15-cal) on cellular respiration of mouse tissues. O(2) consumption by lung, liver, kidney, spleen, and pancreatic tissues was unaffected by exposure to 200 μg/mL MCM41-cal or SBA15-cal for several hours. Normal tissue histology was confirmed by light microscopy. Intracellular accumulation of the particles in the studied tissues was evident by electron microscopy. The results show reasonable in vitro biocompatibility of the mesoporous silicas with murine tissue bioenergetics.

The infective larva of the spirurid nematode Habronema muscae, a parasite of houseflies, was measured and specimens fixed in Karnovsky's fluid were examined by scanning electron microscopy. The oral opening contains six teeth and is surrounded by large bilobed dorsal and ventral lips and smaller lateral lips. A pair of amphids lie behind the lateral lips. There are two rows of four cephalic papillae. The body is deeply ridged, both transversely and longitudinally. The caudal end of the worm is studded by small papillae. The position of the anal opening is somewhat ambiguous. These larval morphological features are discussed, as well as the changes which must have occurred in the metamorphosis of the infective larva to the adult in the stomach of horses.

Overdose of acetaminophen (APAP) causes tissue injury particularly in the liver. However, the precise mechanism of APAP toxicity is not clear. Glutathione (GSH) depletion and oxidative stress are believed to be the main cause of APAP toxicity. The role of macrophages in APAP-induced tissue injury is controversial. Using mouse macrophage J774.2 cells, we recently demonstrated that like in animal models, APAP reduces GSH pool and alters GSH metabolism by increasing the production of reactive oxygen species (ROS). In the present study, we show that APAP-induced cytotoxicity and apoptosis in macrophages are associated with increased mitochondrial metabolic and oxidative stress, alterations in the mitochondrial membrane potential and activities of the respiratory enzyme complexes. APAP treatment also altered ROS/NO production and inhibited the expression of COX-2 and iNOS in LPS-stimulated macrophages. Electron microscopic studies also confirmed morphological changes associated with apoptosis at the lower dose of APAP, while at the higher dose late apoptosis/necrotic changes were visible. These results suggest that mitochondrial metabolic and oxidative stress are the main causes of cytotoxicity and cell death in APAP treated macrophages. The study may have long term implications to better understand the role of macrophages in the toxicology and pharmacology of APAP.

Gastric pathology is a common complication in diabetes mellitus. The aim of the study was to evaluate the functions and morphological changes of the parietal cells of the rat stomach after streptozotocin-induced diabetes. Diabetes mellitus was induced in Wistar rats by a single intraperitoneal injection of streptozotocin (60 mg/kg body weight). The rats were weighed weekly and sacrificed after 6 months. The glandular portion of the stomach was removed and processed for H+-K+-ATPase immunohistochemistry and light and electron microscopy studies. Acid secretion was measured in vivo. After 6 months of diabetes, the mean weight of the rats was significantly lower (P < 0.001) compared to control. The mean weight of the stomach to body weight percentage increased significantly (P < 0.001) compared to control. The blood glucose level in diabetic rats was significantly higher (P < 0.001) than in normal control. Diabetic rats showed significant (P < 0.001) decrease in basal and stimulated acid secretion when compared to control. Electron micrographs of the parietal cells of glandular stomach of diabetic rats revealed significant (P < 0.0002) reduction in the number of mitochondria and a small though not significant increase in the number of canaliculi in the parietal cells compared with normal. Immunohistochemistry showed reduced H+-K+-ATPase (P < 0.00001) compared to control. Long-term diabetes induces morphological as well as functional changes in gastric parietal cells. The decrease in the number of mitochondria accompanied by reduced in H+-K+-ATPase in parietal cells may explain the reduced acid secretion observed in diabetics.

The prevalence of diabetes mellitus (DM) is about 6 % across the globe. This prevalence has been reported to increase in the near future. This means that the number of women with DM who would like to get pregnant and have children will also increase. The present study is aimed at investigating the morphological changes observed in the uterus after the onset of DM. The study also examined the pattern of distribution of nociceptin (NC), a neuropeptide involved in the regulation of pain, a major physiological factor during parturition. The study shows a severe atrophy of uteri as early as 15 days post DM and continued until the termination of the eight-week study. This atrophy was confirmed by light microscopy. Electron microscopy study showed atrophy of the columnar cells of the endometrium, reduced myofibril number and destruction of smooth muscle cells in the myometrium of diabetic rats compared to control. Immunofluorescence and immunoelectron microscopy studies clearly demonstrated the presence of NC in the endometrium, myometrium and on the myofibrils of the smooth muscles of both control and diabetic rat uteri. In addition, NC-positive neurons and varicose fibres were observed in the myometrium of both normal and diabetic rats. However, the expression of NC decreased after the onset of DM. Morphometric analysis showed that the number of NC-labeled cells was significantly (p

Hyperthermia is teratogenic to human and animal embryos and induces mainly anomalies of the nervous system. However, the teratogenic mechanism is poorly understood. Mammalian embryos are known to switch from anaerobic to aerobic metabolism around the time of neural tube closure. This critical event might be sensitive to hyperthermia. The objective of the present study was to evaluate the ultrastructural changes of the mitochondria of the neuroepithelium (NE) of rat embryos following maternal exposure to hyperthermia. Pregnant rats were heat stressed for an hour on gestation day (GD) 9 and embryos were examined by electron microscopy on GD 10. NE presented extensive apoptosis. Intercellular junctions were weakened and copious cellular debris projected into the ventricle. The mitochondria were of diverse size and shape. Most of them were swollen and had short cristae and electron dense matrix. Hydropic changes were also observed in numerous mitochondria. Lipid-laden mitochondria were found in the apical portions of neuroblasts. The mesenchyme (ME) of heat-treated embryos showed paucity of cells and only as frequent apoptosis as the controls. Their mitochondria also showed changes similar to those of the NE. Additionally extensive lipid accumulation was observed in and in the vicinity of mitochondria, often surrounded by short strands of endoplasmic reticulum. Whereas mitochondrial pathology was associated with profound apoptosis in the NE, growth restriction and lipid accumulation accompanied mitochondrial changes in the ME. The results of this study indicate that the embryonic response to maternal heat shock is tissue-specific and morphologically distinct in this species.

The objective of this study was to evaluate the ultra-structural changes in the urinary bladder of diabetic rats in relation to disease duration since the morphological bases of diabetes-induced bladder dysfunction are poorly understood. Urinary bladders were examined chronologically by electron microscopy in a female Wistar-rat model of streptozotocin-induced diabetes mellitus and compared to control samples. Numerous dark mitochondria with swollen cristae and electron lucent, large, calcified and degenerated mitochondria were observed first in the urothelium. Intraepithelial capillaries surrounded by thick collagen were also present. Gap junctions between myocytes were interrupted or extensively widened with reduced mitochondria and caveolae. Collagen accumulation, degenerated nerve fibres and myelin bodies were seen between myocytes with increased collagen content and frequent mast cells, phagocytes and lymphocyte aggregates in the stroma. All ultra-structural lesions became augmented with longer duration of diabetes. Diabetes induces time-dependent pathologic changes in the urinary bladder of rats that might account for bladder dysfunction.

The C57BL/6J mouse has a genetic susceptibility to develop diabetes when fed with a high-fat, high-sucrose diet. The general characteristics of diet-induced diabetes in this model include progressive development of hyperinsulinaemia, hyperglycaemia, insulin resistance and obesity, features that are frequently observed in the clinical setting. This study investigated the progressive effects of a fat enriched (FE) diet on contraction and intracellular Ca2+ in ventricular myocytes from the C57BL/6J mouse. The characteristics of the mice fed with the FE diet compared to mice receiving control diet included progressive increase in the rate of body weight gain, increased fasting blood glucose and time-dependent differences in the disposal of blood glucose after a glucose challenge. The ultrastructure of cardiac myocytes and associated capillaries did not show any gross morphological alteration after 27 weeks of FE diet compared to controls. At 5 months the resting cell length (RCL) and the kinetics of shortening were not significantly altered in ventricular myocytes from mice receiving the FE diet compared to age-matched controls. At 5 and at 7 months the amplitude of shortening was increased in myocytes receiving the FED diet compared to controls. At 7 months the time to half (THALF) relaxation of myocyte contraction was shortened in myocytes from mice receiving the FE diet compared to controls. Mean THALF relaxation in myocytes from mice fed the FE diet was 32.0 +/- 1.4 ms (n = 23) compared to 40.2 +/- 2.0 ms (n = 27) in controls. Neither resting intracellular Ca+ nor the kinetics or amplitude of the Ca2+ transient were altered by FE diet. Differences in myofilament sensitivity to Ca2+ might underlie the changes in contractility.

Rats develop hyperalgesia and allodynia in the hind paw after L5 spinal nerve ligation. Phosphorylated extracellular regulated kinase (pERK) was used as a pain marker to investigate the potential role of adjacent uninjured L4 nerve in the development of heat hyperalgesia after L5 nerve injury. Left L5 nerve was ligated and sectioned in rats. Three days later, rats were randomly assigned to five groups; each had both hind paws immersed in water at different temperatures (no heat, 37, 42, 47, and 52 °C) under sevoflurane anesthesia for 2 minutes. Five minutes after stimulation the rats were sacrificed and sections of L3-L6 spinal segments were stained immunocytochemically with pERK antibody. pERK immunoreactivity, which is not detectable in the normal spinal cord, was discernible in neurons (not glia) of the superficial dorsal horn after noxious heat stimuli. pERK-positive neurons clearly overlapped in laminae I-II with normal unmyelinated and thin myelinated afferents labeled with calcitonin gene-related peptide and isolectin B4, and injured unmyelinated afferents labeled with vasoactive intestinal polypeptide. There was a linear increase in pERK immunoreactivity on both sides with an increase in temperature. Importantly, the number of positive pERK neurons was significantly higher in the ipsilateral side of L4 spinal segment, which receives innervation from uninjured L4 nerve, compared with the contralateral control side, which receives both uninjured L4 and L5 spinal nerves. The data demonstrate that the uninjured L4 nerve plays an important role in the development of heat hyperalgesia at the spinal cord level after L5 nerve injury.

Incretins, such as glucagon-like peptide-1 (GLP)-1, have been shown to elevate plasma insulin concentration. The purpose of this study is to investigate the cellular and molecular basis of the beneficial effects of GLP-1. Normal and diabetic male Wistar rats were treated with GLP-1 (50 ng/kg body weight) for 10 weeks. At the end of the experiment, pancreatic tissues were taken for immunohistochemistry, immunoelectron microscopy and real-time polymerase chain reaction studies. Samples of blood were retrieved from the animals for the measurement of enzymes and insulin. The results show that treatment of diabetic rats with GLP-1 caused significant (P

Glucagon-like peptide 1 (GLP1) agonists are promising therapeutic agents in the treatment of diabetes mellitus. This study examines the mechanism of the protective effects of exenatide in experimental diabetes, employing four groups of ten rats each, in which two groups were streptozotocin-induced diabetic and two were control groups. One control and one diabetic group were treated with exenatide (1 μg/kg body weight (BW)) for 10 weeks. Blood plasma was taken for biochemical analyses while pancreatic tissue was taken for immunofluorescence and immunoelectron microscopy studies and real-time PCR to examine the expression of genes. The results show that exenatide improved BW gain and reduced blood glucose in diabetic rats compared with controls. Similarly, exenatide enhanced insulin release from the pancreatic fragments and improved liver and kidney functions and lipid profile in diabetic rats compared with controls. Exenatide not only induced significant increases in serum insulin level but also elevated the number of insulin-, GLP1- and exenatide-positive cells compared with untreated controls. Exenatide also elevated the number of catalase- and glutathione reductase-positive cells in diabetic rat pancreas compared with controls. Exenatide caused significant elevation in the expressions of pancreatic duodenal homeobox-1, heat shock protein-70, glutathione peroxidase, insulin receptor and GLP1 receptor genes in the pancreas of both control and diabetic rats compared with untreated animals. The results have demonstrated that exenatide can exert its beneficial and protective effects by elevating the levels of endogenous antioxidants and genes responsible for the survival, regeneration and proliferation of pancreatic β-cell.

In vivo and in vitro systems were employed to investigate the biocompatibility of two forms of calcined mesoporous silica microparticles, MCM41-cal and SBA15-cal, with ventricular myocytes. These particles have potential clinical use in delivering bioactive compounds to the heart. Ventricular myocytes were isolated from 6 to 8 week male Wistar rats. The distribution of the particles in ventricular myocytes was investigated by transmission electron microscopy and scanning electron microscopy. The distribution of particles was also examined in cardiac muscle 10 min after intravenous injection of 2.0 mg/mL MCM41-cal. Myocyte shortening and the Ca(2+) transient were determined following exposure to 200 μg/mL MCM41-cal or SBA15-cal for 10 min. Within 10 min of incubation at 25 °C, both MCM41-cal and SBA15-cal were found attached to the plasma membrane, and some particles were observed inside ventricular myocytes. MCM41-cal was more abundant inside the myocytes than SBA15-cal. The particles had a notable affinity to mitochondrial membranes, where they eventually settled. Within 10 min of intravenous injection (2.0 mg/mL), MCM41-cal traversed the perivascular space, and some particles entered ventricular myocytes and localized around the mitochondrial membranes. The amplitude of shortening was slightly reduced in myocytes superperfused with MCM41-cal or SBA15-cal. The amplitude of the Ca(2+) transient was significantly reduced in myocytes superperfused with MCM41-cal but was only slightly reduced with SBA15-cal. Overall, the results show reasonable bioavailability and biocompatibility of MCM41-cal and SBA15-cal with ventricular myocytes.

Nociceptin and nocistatin are endogenous ligands of G protein coupled receptor family. Numerous techniques have been used to study the diverse parameters including, localization, distribution and ultrastructure of these peptides. The majority of the study parameters are based on their physiological roles in different organ systems. The present study presents an overview of the different methods used for the study of nociceptin, nocistatin and their receptors. Nociceptin has been implicated in many physiological functions including, nociception, locomotion, stressed-induced analgesia, learning and memory, neurotransmitter and hormone release, renal function, neuronal differentiation, sexual and reproductive behavior, uterine contraction, feeding, anxiety, gastrointestinal motility, cardiovascular function, micturition, cough, hypoxic–ischemic brain injury, diuresis and sodium balance, temperature regulation, vestibular function, and mucosal transport. It has been noted that the use of light and electron microscopy was less frequent, though it may be one of the most promising tools to study the intracellular localization of these neuropeptides. In addition, more studies on the level of circulating nociceptin and nocistatin are also necessary for investigating their clinical roles in health and disease. A variety of modern tools including physiological, light and electron microscopy (EM) are needed to decipher the extent of intracellular localization, tissue distribution and function of these peptides. The intracellular localization of nociceptin and nocistatin will require a high resolution transmission EM capable of identifying these peptides and other supporting molecules that co-localize with them. A tracing technique could also elucidate a possible migratory ability of nociceptin and nocistatin from one cellular compartment to the other.

We report on the pneumatocyte structure and function of mouse lung specimens exposed in vitro to two calcined mesoporous silica particles, MCM41-cal (spheres, ∼300 to 1000 nm in diameter) and SBA15-cal (irregular rods averaging ∼500 nm in diameter and ∼1000 nm in length). These mesoporous silica particles are in consideration for potential medical application as delivery vehicles for genes, drugs, and bio-imagers. In the study, lung specimens (about 10 mg each) were excised from male Balb/c mice, immediately immersed in Krebs-Henseleit buffer, ice-cold, and continuously gassed with O(2):CO(2) (95:5). The samples were incubated at 37°C in the same buffer with and without 200 μg/mL MCM41-cal or SBA15-cal for 5-14 h. The tissues were then rinsed thoroughly and processed for light and electron microscopy. Normal alveolar morphology was evident in all the studied specimens. There was no significant difference in the number of apoptotic cells between the treated and untreated samples. Despite their relatively large sizes, the particles were abundantly present in pneumocytes, macrophages, endothelial cells, fibroblasts, and interstitium. They were seen in different areas of the cytoplasm, suggesting intracellular movements. Their presence did not appear to disturb cellular configuration or micro-organelles. Due to their rigidity and surface charges, some were firmly attached to (indenting) the nuclear membrane. The rate of respiration (cellular mitochondrial O(2) consumption, in μM O(2)/min/mg) in specimens exposed to 200 μg/mL particles for up to 12 h was the same as untreated specimens. These findings confirm "reasonable" bioavailability and biocompatibility of calcined mesoporous silicas with mouse lung within at least 5-14 h of exposure time.

The morphological and biochemical changes that occur in the early phase of streptozotocin (STZ)-induced beta cell failure have not been characterized. The pancreas and plasma of rats treated with STZ were processed for morphological and biochemical parameters 1-24 h and 4 weeks after STZ treatment. Marked reduction in body weight was observed as early as 3 h post STZ treatment and hyperglycemia coupled with hypoinsulinaemia appeared in rats 1 h after treatment with STZ. Hyperglycemia, hyperglucagonemia and hypoinsulinemia became permanent 24 h after STZ treatment. The number of insulin-positive cells decreased significantly (p

The visceral pleura of the camel (Camelus dromedarius) possesses a fibrous curtain of pleural threads or extensions along its basal margins, which extends into the pleural cavity of the costophrenic recesses. These threads are lined by mesothelium and have a core or stroma, which is largely collagenous. Small threads are avascular and nearly acellular. In larger proximal threads, blood vessels in the stroma are often arranged in a branching network, with irregular endothelia surrounded by several incomplete basal laminae. Lymphocytes and other inflammatory cell types aggregate in the stroma near blood vessels. The threads are lined by typical mesothelium except in patches close to the main pleural surface. These patches consist of layers of loosely applied cells with numerous cellular processes and features suggestive of phagocytosis. The position of the pleural curtain in the costophrenic recess and the presence of possibly phagocytotic cells suggest that the pleural curtain stirs, samples, and cleans the pleural fluid. The pleural curtain appears to be a feature of camelids and has also been seen in giraffes.

The distribution and relative frequency of neuroendocrine cells in the small and large intestines of one-humped camel were studied using antisera against 5-hydroxytryptamine (5-HT), cholecystokinin (CCK-8), somatostatin (SOM), peptide tyrosine tyrosine (PYY), gastric inhibitory polypeptide (GIP), neuronal nitric oxide synthase (nNOS), gastrin releasing peptide (GRP), substance P (SP), and neurokinin A (NKA). Among these cell types, CCK-8 immunoreactive (IR) cells were uniformly distributed in the mucosa, while others showed varied distribution in the villi or crypts of the small intestine. Immunoreactive cells like 5HT, CCK-8, and SOM showed peak density in the villi and crypts of the small intestine and in the colonic glands of the large intestine, while cells containing SP were discerned predominately in the crypts. 5-HT, CCK-8 and SOM cells were mainly flask-shaped and of the open-variety, while PYY and SP immunoreactive cells were mainly rounded or basket-shaped and of the closed variety. Basically the distribution pattern of the endocrine cells in the duodenum, jejunum and colon of the one-humped camel is similar to that of other mammals. Finally, the distribution of these bioactive agents may give clues as to how these agents aid in the function of the intestinal tract of this desert animal.

Adult male rhesus monkeys (Macaca mulatta) were given oral treatment of either Aroclor 1242 or vehicle (corn oil and glycerol) at a dose of 200 microg/kg body wt/day for 6 months to investigate the effects of the pollutant on plasma testosterone and the morphology of testes and accessory glands. Aroclor 1242 treatment significantly decreased testicular size and testosterone levels in plasma and adversely affected spermatogenic activity by disrupting epithelial organization. All components of the germinal epithelium were greatly reduced. The spermatogonia were either hypertrophied or had shrunken vesiculated cytoplasm with distorted mitochondria and nuclear pyknosis. Changes were milder in the Sertoli cells, where nuclear infoldings were reduced. Characteristic features of treated Leydig cells were the presence of electron-dense and electron-opaque zones, appearing as plaques, cell membrane abnormalities, and high variability in nuclear shape and heterochromatin distribution. All the Aroclor 1242-treated accessory glands contained more connective tissue than their vehicle-treated counterparts. The epithelium contained many layers of irregularly shaped necrotic cells possessing stereocilia in the epididymides, either hypochromic and hypertrophied or hyperchromic and hypotrophied cells in the prostate and shrunken cuboidal cells with elongated nuclei in the seminal vesicles. In conclusion, Aroclor 1242 treatment causes severe structural alterations on gonads and accessory organs in adult male rhesus monkeys, and these effects could be mediated through both estrogen and Ah receptors.

Mohammed T Al Samri,1,* Rafael Silva,2,* Saeeda Almarzooqi,3 Alia Albawardi,3 Aws Rashad Diab Othman,1 Ruqayya SMS Al Hanjeri,1 Shaikha KM Al Dawaar,1 Saeed Tariq,4 Abdul-Kader Souid,1 Tewodros Asefa2,51Department of Pediatrics, United Arab Emirates University, Abu Dhabi, United Arab Emirates; 2Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ, USA; 3Department of Pathology, 4Department of Anatomy, United Arab Emirates University, Abu Dhabi, United Arab Emirates; 5Department of Chemical Engineering and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, USA*These authors contributed equally to this workAbstract: We present here comparative assessments of murine lung toxicity (biocompatibility) after in vitro and in vivo exposures to carbon (C–SiO2-etched), carbon–silica (C–SiO2), carbon–cobalt–silica (C–Co–SiO2), and carbon–cobalt oxide–silica (C–Co3O4–SiO2) nanoparticles. These nanoparticles have potential applications in clinical medicine and bioimaging, and thus their possible adverse events require thorough investigation. The primary aim of this work was to explore whether the nanoparticles are biocompatible with pneumatocyte bioenergetics (cellular respiration and adenosine triphosphate content). Other objectives included assessments of caspase activity, lung structure, and cellular organelles. Pneumatocyte bioenergetics of murine lung remained preserved after treatment with C–SiO2-etched or C–SiO2 nanoparticles. C–SiO2-etched nanoparticles, however, increased caspase activity and altered lung structure more than C–SiO2 did. Consistent with the known mitochondrial toxicity of cobalt, both C–Co–SiO2 and C–Co3O4–SiO2 impaired lung tissue bioenergetics. C–Co–SiO2, however, increased caspase activity and altered lung structure more than C–Co3O4–SiO2. The results indicate that silica shell is essential for biocompatibility. Furthermore, cobalt oxide is the preferred phase over the zerovalent Co(0) phase to impart biocompatibility to cobalt-based nanoparticles.Keywords: carbon nanoparticles, cobalt nanoparticles, silica nanoparticles, cobalt oxide nanoparticles, biocompatibility, nanotoxicology