The thymus is a central lymphoid organ for T cell development. Thymic epithelial cells (TECs) constitute a major component of the thymic stroma, which provides a specialized microenvironment for survival, proliferation, and differentiation of immature T cells. In this study, subsets of TECs were examined immunohistochemically to investigate their cytokeratin (CK) expression patterns during thymus regeneration following thymic involution induced by cyclophosphamide treatment. The results demonstrated that both normal and regenerating mouse thymuses showed a similar CK expression pattern. The major medullary TECs (mTEC) subset, which is stellate in appearance, exhibited CK5 and CK14 staining, and the minor mTEC subset, which is globular in appearance, exhibited CK8 staining, whereas the vast majority of cortical TECs (cTECs) expressed CK8 during thymus regeneration. Remarkably, the levels of CK5 and CK14 expression were enhanced in mTECs, and CK8 expression was upregulated in cTECs during mouse thymus regeneration after cyclophosphamide-induced acute thymic involution. Of special interest, a relatively high number of CK5(+)CK8(+) TEC progenitors occurred in the thymic cortex during thymus regeneration. Taken together, these findings shed more light on the role of CK5, CK8, and CK14 in the physiology of TECs during mouse thymus regeneration, and on the characterization of TEC progenitors for restoration of the epithelial network and for concomitant regeneration of the adult thymus.
Oxidative stress-induced cell death leads to phosphorylation of 14-3-3ζ at serine 58. 14-3-3ζ is detected at significant levels in cerebrospinal fluid after kainic acid (KA)-induced seizures. Here we examined temporal changes in 14-3-3ζ phosphorylation in the hippocampus and amygdala of mice after KA treatment. Mice were killed at 2, 6, 24, or 48 h after KA (30 mg/kg) injection. We observed an increase in TUNEL and Fluoro-Jade B (FJB)-stained neurons in the hippocampus and amygdala of KA-treated mice. Phospho (p)-14-3-3ζ and p-JNK expression was increased in the hippocampus 2 and 6 h after KA treatment, respectively. In immunohistochemical analysis, p-14-3-3ζ-positive cells were present in the CA3 region of the hippocampus and the central nucleus of amygdala (CeA) of KA-treated mice. Thus, phosphorylation of 14-3-3ζ at serine 58 may play an important role in KA-induced hippocampal and amygdaloid neuronal damage.
Connexin-43, a major gap junction protein, and cytokeratin-19, one of the intermediate filament keratins, are known to be markers of well-differentiated epithelium. In this study, we investigated the expression of these markers in the head region, lungs, and abdominal organs of 10 human mid-term fetuses. The expression of connexin-43 was found to be restricted to the dura mater, kidney, and adrenal cortex. In the kidney, we found a clear site-dependent difference in the expression pattern of these markers: connexin-43 expression was observed in the tubules of the renal cortex whereas cytokeratin-19 was strongly expressed in the collecting ducts and renal pelvis. This difference remained unchanged throughout the fetal stages examined. Immunoreactivity was not observed for either of the markers in the intrarenal vessels, including the glomeruli, and mesangial cells. Connexin-43 expression seemed to be restricted to the metanephric vesicle-derived structures that differentiate in the urogenital ridge of the splanchnic mesoderm. The adrenal cortex also originates from the same para-aortic mesoderm. In contrast, in the urogenital organs, cytokeratin-19 seemed to be expressed in ducts derived from the urogenital sinus.
Voltage dependent calcium channels (VDCC) participate in regulation of neuronal Ca(2+). The Rolling mouse Nagoya (Cacna1a(tg-rol)) is a spontaneous P/Q type VDCC mutant, which has been suggested as an animal model for some human neurological diseases such as autosomal dominant cerebellar ataxia (SCA6), familial hemiplegic migraine and episodic ataxia type-2. Morphology of Purkinje cell (PC) dendritic spine is suggested to be regulated by signal molecules such as Ca(2+) and by interactions with afferent inputs. The amplitude of excitatory postsynaptic current was decreased in parallel fiber (PF) to PC synapses, whereas apparently increased in climbing fiber (CF) to PC synapses in rolling mice Nagoya. We have studied synaptic morphology changes in cerebella of this mutant strain. We previously found altered synapses between PF varicosity and PC dendritic spines. To study dendritic spine plasticity of PC in the condition of insufficient P/Q type VDCC function, we used high voltage electron microscopy (HVEM). We measured the density and length of PC dendritic spines at tertiary braches. We observed statistically a significant decrease in spine density as well as shorter spine length in rolling mice compared to wild type mice at tertiary dendritic braches. In proximal PC dendrites, however, there were more numerous dendritic spines in rolling mice Nagoya. The differential regulation of rolling PC spines at tertiary and proximal dendrites in rolling mice Nagoya suggests that two major excitatory afferent systems may be regulated reciprocally in the cerebellum of rolling mouse Nagoya.
In rats, ageing results in dysfunctional patterns of micturition and diminished sexual reflexes that may reflect degenerative changes within spinal circuitry. In both sexes the dorsal lateral nucleus and the spinal nucleus of the bulbospongiosus, which lie in the L5-S1 spinal segments, contain motor neurons that innervate perineal muscles, and the external anal and urethral sphincters. Neurons in the sacral parasympathetic nucleus of these segments provide autonomic control of the bladder, cervix and penis and other lower urinary tract structures. Interneurons in the dorsal gray commissure and dorsal horn have also been implicated in lower urinary tract function. This study investigates the cellular localisation of PG-21 androgen receptors, steroid receptor co-activator one (SRC-1) and the phosphorylated form of c-AMP response element binding protein (pCREB) within these spinal nuclei. These are components of signalling pathways that mediate cellular responses to steroid hormones and neurotrophins. Nuclear expression of PG-21 androgen receptors, SRC-1 and pCREB in young and aged rats was quantified using immunohistochemistry. There was a reduction in the number of spinal neurons expressing these molecules in the aged males while in aged females, SRC-1 and pCREB expression was largely unchanged. This suggests that the observed age-related changes may be linked to declining testosterone levels. Acute testosterone therapy restored expression of PG-21 androgen receptor in aged and orchidectomised male rats, however levels of re-expression varied within different nuclei suggesting a more prolonged period of hormone replacement may be required for full restoration.
AMP-activated protein kinase (AMPK), an enzyme involved in energy homeostasis, regulates inflammatory responses, but its precise mechanisms are not fully understood. Recent evidence has shown that resveratrol (RES), an AMPK activator, reduces prostaglandin E(2) production in lipopolysaccharide (LPS)-treated microglia. Here, we examined the effect of RES on nuclear factor kappa B (NF-κB) dependent cyclooxygenase (COX)-2 activation in LPS-treated RWA 264.7 macrophages. We found that treatment with RES increased AMPK activation. AMPK and acetyl CoA carboxylase phosphorylation were attenuated in cells treated with LPS+RES, compared to cells treated with LPS alone. RES inhibited tumor necrosis factor (TNF)-α and TNF receptor 1 in LPS-treated cells. Finally, RES inhibited LPS-induced NF-κB translocation into the nucleus and COX-2 expression. Moreover, the effects of 5-aminoimidazole-4-carboxamide ribose and compound C were consistent with the effects of RES in LPS-treated cells. Taken together, these results suggest that the anti-inflammatory action of RES in RAW 264.7 macrophages is dependent on AMPK activation and is associated with inhibition of the LPS-stimulated NF-κB-dependent COX-2 signaling pathway.
The high resistance to infections in lizard wounds suggests that these reptiles possess effective antimicrobial peptides in their tissues. The present immunocytochemical study shows the cellular localization of beta-defensin 27 in tail tissues and in the blood, a defensin previously identified in the lizard Anolis carolinensis through biomolecular methods. Beta-defensin-27 immunoreactivity is only observed in some large granules mainly contained in heterophilic granulocytes that are sparse within the dermis of the skin or in the isolated blood. This peptide is absent in other cell types of the skin, in keratinocytes and in subdermal muscle tissue of the tail in normal conditions. Pre-corneous keratinocytes of the regenerating tail epidermis are unlabeled or show a weak labeling for the peptide only in sparse cytoplasmic areas or in the extracellular spaces among corneocytes of the wound and regenerating epidermis. The study suggests that beta-defensin 27 is normally stored in granulocytes present in the blood or in connective tissues while in the epidermis keratinocytes do not show the presence of this peptide unless these cells are stimulated from injury to produce and likely release beta-defensins.
Mast cells participate in allergies and inflammation by secreting a variety of pro-inflammatory mediators. Curcumin, the active component of turmeric, is a polyphenolic phytochemical with anti-tumor, anti-inflammatory, anti-oxidative, and anti-allergic properties. The effects of curcumin on compound 48/80-induced mast cell activation and passive cutaneous anaphylactoid reactions are unknown. In this report, we investigated the influences of curcumin on the passive cutaneous anaphylactoid response in vivo and compound 48/80-induced mast cell activation in vitro. The mechanism of action was examined by calcium uptake measurements and cAMP assays in mast cells. Curcumin significantly attenuated the mast cell-mediated passive cutaneous anaphylactoid reaction in an animal model. In agreement with this in vivo activity, curcumin suppressed compound 48/80-induced rat peritoneal mast cell (RPMC) degranulation and histamine release from RPMCs. Moreover, compound 48/80-elicited calcium uptake into RPMCs was reduced in a dose-dependent manner by curcumin. Furthermore, curcumin increased the level of intracellular cAMP and significantly inhibited the compound 48/80-induced reduction of cAMP in RPMCs. These results corroborate the finding that curcumin may have anti-allergic activity.
Alpha-lipoic acid (LA), a naturally occurring dithiol compound, is an essential cofactor in metabolic reactions involved in energy utilization. LA improves glycemic control, reduces diabetic polyneuropathies, atherosclerosis, and allergic inflammation. The effects of LA on mast cell-mediated anaphylactic reactions, however, are unknown. LA dose-dependently inhibited systemic and passive cutaneous anaphylaxis-like reactions in mice induced by compound 48/80, a condensation product of N-methyl-p-methoxyphenethylamine and formaldehyde. Pretreatment with LA, prior to induction of the systemic anaphylaxis-like reaction with compound 48/80, reduced plasma histamine levels in a dose-dependent manner. In our in vitro study, LA decreased histamine release from rat peritoneal mast cells (RPMCs) triggered by compound 48/80. Moreover, an increase in calcium uptake activated by compound 48/80 was inhibited by LA. LA also significantly elevated intracellular cyclic adenosine-3',5' monophosphate (cAMP) levels in RPMCs. This inhibition of mediator release from RPMCs may be due to inhibition of calcium uptake and augmentation of intracellular cAMP levels. Based on these results, we suggest that LA may be a potential remedy for allergy-related diseases.
Women with tubal ectopic pregnancies have high levels of circulating interleukin 6 (IL-6). IL-6 treatment in vitro significantly reduces the ciliary activity of tubal epithelium. The effects of IL-6 on target cells occur via the formation of a high-affinity complex with its receptors IL-6Rα and glycoprotein 130 (Gp130). IL-6Rα is specifically expressed in the cilia of the epithelial cells. In this study, we performed a quantitative reverse transcriptase polymerase chain reaction to determine the mRNA expression of IL-6Rα and Gp130 in the fallopian tubes obtained from 12 women with ectopic pregnancies, 12 women with normal pregnancies, and 12 healthy nonpregnant women in the luteal phase of their menstrual cycle. Fallopian tubes were evaluated from specimens taken during tubal ligation in normal pregnancies and nonpregnant fertile women or during tubal surgery in ectopic pregnancies. We observed that IL-6Rα mRNA expression in fallopian tubes was increased in ectopic pregnancy compared with that in the midluteal phase. We also found that the Gp130 mRNA expression was significantly lower in fallopian tubes from ectopic pregnancies than in those from nonpregnant women during the midluteal phase of their menstrual cycle, although its expression was noticeably high in fallopian tubes in the midluteal phase, which suggests that high Gp130 levels may possibly contribute to embryo transport into the uterus.
The regular extract of Ginkgo biloba has been shown to possess neuroprotective properties in disorders like hypoxia, ischemia, seizure activity and peripheral nerve damage. Also, G. biloba has received attention as a potential cognitive enhancer for the treatment of Alzheimer's disease, but there is not any documentation about the effect of an extract of G. biloba on astrocytes. Therefore, the aim of this study was examined the effects of G. biloba extract on the rat's hippocampal astrocytes after scopolamine based amnesia. In this study, 36 adult male Wistar rats were used. Rats were randomly distributed into control, sham, protective and treatment groups. The rats in the sham group only received scopolamine hydrobromide (3 mg/kg) intraperitoneally. The rats in the protective and treatment groups received G. biloba extract (40, 80 mg/kg) for 7 days intraperitoneally before and after scopolamine injection. Forty eight hours after the last injection, the brains of the rats were withdrawn and fixed with paraformaldehide, and then after histological processing, the slices were stained with phosphotungstic acid-haematoxylin for astrocytes. Data were analyzed by the analysis of variance (ANOVA) post hoc Tukey test; P<0.05 was considered significant. Results showed that scopolamine can reduce the number of astrocytes in all areas of hippocampal formation compared with the control. However, G. biloba extract can compensate for the reduction in the number of astrocytes in the hippocampus before or after the encounter with scopolamine. We concluded that a pretreatment and treatment injection of G. biloba extract can have a protective effect for astrocytes in all areas of hippocampal formation.
Vascular anomalies are frequently encountered in abdomen. But they are usually asymptomatic and diagnosed accidently during angiography or surgery leading into severe complications. Thus knowledge of angioarchitecture in abdomen, whether normal or variant, is considered prerequisite for successful, uncomplicated surgeries and interventional radiology. This case report describes one of such varying branching pattern of celiac trunk and superior mesenteric artery. During routine abdominal dissection, gastroduodenal artery was seen arising from celiac trunk along with its usual three branches. Common hepatic artery continued as left hepatic artery after giving rise the right gastric artery and a tortuous replaced right hepatic artery arose from superior mesenteric artery. An unusually long cystic artery arose from left hepatic artery and gave rise to 2-3 small anastomotic branches towards hepatic flexor of colon, in addition to its normal gallbladder supply. Awareness of such variations would certainly be helpful in upper abdominal surgeries.
We report on an extremely rare case of multiple absences of the branches of abdominal aorta with congenital absence of the portal vein, unilateral adrenal agenesis and persistent ductus arteriosus in an adult female cadaver. Specifically, instead of celiac trunk, superior and inferior mesenteric arteries, solely a single arterial trunk aroused from the anterior aspect of abdominal aorta, inferior phrenic and ovarian arteries were absent in both sides. Left kidneys drained by two veins. There were not superior, splenic and mesenteric veins, while left renal vein received an additional vein, which run downward and drained primarily all parts of digestive tract and its associated glands (portal vein did not exist). Right adrenal gland was absent. To the best of our knowledge, it is the only reported case with such widespread anomalies. We think the importance of this case is beyond the surgical consideration and needs more profound developmental studies.
A term "mesoesophagus" has been often used by surgeons, but the morphology was not described well. To better understand the structures attaching the human abdominal and lower thoracic esophagus to the body wall, we examined serial or semiserial sections from 10 embryos and 9 fetuses. The esophagus was initially embedded in a large posterior mesenchymal tissue, which included the vertebral column and aorta. Below the tracheal bifurcation at the fifth week, the esophagus formed a mesentery-like structure, which we call the "mesoesophagus," that was sculpted by the enlarging lungs and pleural cavity. The pneumatoenteric recess of the pleuroperitoneal canal was observed in the lowest part of the mesoesophagus. At the seventh week, the mesoesophagus was divided into the upper long and lower short parts by the diaphragm. Near the esophageal hiatus, the pleural cavity provided 1 or 2 recesses in the upper side, while the fetal adrenal gland in the left side was attached to the lower side of the mesoesophagus. At the 10th and 18th week, the mesoesophagus remained along the lower thoracic esophagus, but the abdominal esophagus attached to the diaphragm instead of to the left adrenal. The mesoesophagus did not contain any blood vessels from the aorta and to the azygos vein. The posterior attachment of the abdominal esophagus seemed to develop to the major part of the phrenoesophageal membrane with modification from the increased mass of the left fetal adrenal. After postnatal degeneration of the fetal adrenal, the abdominal esophagus might again obtain a mesentery. Consequently, the mesoesophagus seemed to correspond to a small area containing the pulmonary ligament and aorta in adults.
We found multiple aneurysms in the intracranial arteries and abdominal aorta of an 87-year-old Korean female cadaver, whose cause of death was reported as "cholangiocarcinoma." An abdominal aortic aneurysm was observed in the infrarenal aorta, where the inferior mesenteric artery arose. The intracranial aneurysms were found in the A3 segment of the anterior cerebral artery and at the bifurcation of the middle cerebral artery. This case provides an example of the very rare association of peripheral intracranial aneurysms with an abdominal aortic aneurysm. Clinicians as well as anatomists should recognize the potential association between these two aneurysm types.
Wnt/β-catenin signaling plays a critical role in bone formation and regeneration. Dentin and cementum share many similarities with bone in their biochemical compositions and biomechanical properties. Whether Wnt/β-catenin signaling is involved in the dento-alveolar complex formation is unknown. To understand the roles of Wnt/β-catenin signaling in the dento-alveolar complex formation, we generated conditional β-catenin activation mice through intercross of Catnb(+/lox(ex3)) mice with Col1a1-cre mice. In mutant mice, tooth formation and eruption was disturbed. Lower incisors and molars did not erupt. Bone formation was increased in the mandible but tooth formation was severely disturbed. Hypomineralized dentin was deposited in the crown but roots of molars were extremely short and distorted. In the odontoblasts of mutant molars, expression of dentin matrix proteins was obviously downregulated following the activation of β-catenin whereas that of mineralization inhibitor was increased. Cementum and periodontal ligament were hypoplastic but periodontal space was narrow due to increased alveolar bone formation. While cementum matrix proteins were decreased, bone matrix proteins were increased in the cementum and alveolar bone of mutant mice. These results indicate that local activation of β-catenin in the osteoblasts and odontoblasts leads to aberrant dento-alveolar complex formation. Therefore, appropriate inhibition of Wnt/β-catenin signaling is important for the dento-alveolar complex formation.
Knowledge of the renal vascular anatomy may greatly contribute to the success of surgical, invasive and radiological procedures of the retroperitoneal region. Here, morphometric and histological studies of a human cadaveric specimen presented a complex, anomalous pattern of renal veins. The left renal vein had an oblique retro-aortic course and received two lumbar veins. It bifurcated near its drainage point into the inferior vena cava. The right renal vein received the right testicular vein. In addition, the left kidney was located at a low position. The spleen was enlarged. The present case is unique and provides information that may help surgeons or angiologists to apply safer interventions.
To identify genes that participate in the abortion process, normal pregnant uteri were compared to lipopolysaccharide (LPS)-induced abortion uteri. At day 6 of pregnancy, mice were treated with LPS at various time points to induce an abortion. Total RNAs were applied to a cDNA microarray to analyze genes with altered expression. At the early stage (2 hours) of LPS-induced abortion, upregulated genes were mainly composed of immune responsive genes, including Ccl4, Ccl2, Cxcl13, Gbp3, Gbp2, Mx2, H2-Eb1, Irf1 and Ifi203. Genes related to toll-like receptor signaling were also overexpressed. At late stages of abortion (12-24 hours), many genes were suppressed rather than activated, and these were mainly related to the extracellular matrix, cytoskeleton, and anti-apoptosis. Altered expression of several selected genes was confirmed by real time reverse transcription-polymerase chain reaction. The results demonstrated that many known genes were altered in the LPS-treated pregnant uterus, implying that the molecular mechanisms of the genes involved in LPS-induced abortion are complicated. Further analysis of this expression profile will help our understanding of the pathophysiological basis for abortion.
The palmaris longus (PL) is a slender, spindle-shaped weak flexor of the wrist. Congenital absence of the PL is estimated to occur in 15% among individuals worldwide. However, the frequency of its absence varies considerably among different population groups and with different detection techniques. In the present study, the presence of the PL tendon was examined in a Korean population (n=269) using three clinical tests, namely the Traditional Test, Mishra's Test II, and the Gangata Test. We classified subjects into six types based on whether inspection or palpation was required to determine the presence of the PL and flexor carpi radialis. The most reliable test was determined using Kendall's coefficient of concordance. Our results showed that the PL tendon was absent in 4.1% of the subjects in our study, and bilateral and unilateral absences were 2.2% and 1.8%, respectively. Statistical analysis revealed that these tests had similar reliability for assessing the PL tendon, and the Traditional Test showed the highest effectiveness, at 93%. Therefore the Traditional Test was found to be the most effective for revealing the PL in this Korean population.
Congenital anomalies such as positional anomalies of the right half of the colon are more common when compared to its left half. We report a rare case of congenital anomaly where the transverse colon was totally absent. Ascending colon continued as descending colon at the right colic flexure. Ascending and descending colons formed an inverted U shaped loop which was situated in the right half of the abdomen. The sigmoid colon began from the descending colon, on the right side of the midline and coursed to the left iliac fossa. The terminal part of ascending colon and entire descending colon had a persistent mesocolon. The jejunum and ileum were situated in the upper left part of the abdominal cavity. This anomaly can cause volvulus of the colon at any stage of life. Furthermore, the knowledge of this anomaly is very useful for radiologists, gastroenterologists and surgeons.
A 43-year-old female cadaver showed a complete bilateral absence of the musculocutaneous nerve. The anterior compartment muscles of both arms were supplied by median nerve excepting the coracobrachialis which was innervated by a direct branch from the lateral cord of brachial plexus. The median nerve, after supplying the biceps and brachialis muscles, gave onto the lateral cutaneous nerve of the forearm. The median nerve also showed variation on the left side where it was formed by two lateral roots and one medial root. Variations of the brachial plexus are of great interest to anatomists, clinicians and surgeons, in that they may be incorporated in their day to day practice. Our present case may be noted for its clinical and surgical significance in the variations of brachial plexus which can be useful for diagnostic purposes.
Quantitative studies to date on the effects of opioid consumption and abstinence on the nervous system using modern stereological methods have not received enough attention. In addition, they have yielded controversial results. The present study was conducted to investigate the effects of morphine, with or without abstinence, on the neurons and oligodendrocytes of the medial prefrontal cortex (MPFC) in rats using quantitative stereological methods. The male rats were divided into four groups: the first (saline [SAL]) and second (morphine [MOR]) groups were treated with saline and an escalating dose of morphine (5-20 mg/kg) for 30 days, respectively; the third (SAL+abstinence [ABS]) and fourth (MOR+ABS) groups were treated in the same manner as the previous groups plus they had a 30-day abstinence period. The results showed that the volume of the MPFC and its subdivisions decreased by approximately 15% in the MOR group compared with that in the SAL group (P<0.05). In addition, the volume decreased by approximately 24% in the MOR+ABS group compared with that in the SAL+ABS group (P<0.05). The number of neurons in the MOR and MOR+ABS groups decreased by approximately 44% and 35%, respectively, compared with that in their corresponding control groups. Moreover, the number of the oligodendrocytes in the MOR and MOR+ABS groups decreased by approximately 41% and 37%, respectively. No significant difference was noted in the number of cells in the MOR and MOR+ABS groups. In conclusion, morphine consumption leads to a permanent reduction in the number of neurons and oligodendrocytes, and no additional neuron and oligodendrocyte loss occurs after abstinence.
Muscular variations of the flexor compartment of forearm are usual and can result in multiple clinical conditions limiting the functions of forearm and hand. The variations of the muscles, especially accessory muscles may simulate soft tissue tumors and can result in nerve compressions. During a routine dissection of the anterior region of the forearm and hand, an unusual muscle was observed on the left side of a 65-year-old male cadaver. The anomalous muscle belly arose from the medial epicondyle approxiamately 1 cm posterolateral to origin of normal flexor carpi ulnaris muscle (FCU), and from proximal part of the flexor digitorum superficialis muscle. It inserted to the triquetral, hamate bones and flexor retinaculum. Passive traction on the tendon of accessory muscle resulted in flexion of radiocarpal junction. The FCU which had one head, inserted to the pisiform bone hook of hamate and palmar aponeurosis. Its contiguous muscles displayed normal morphology. Knowledge of the existence of muscle anomalies as well as the location of compression is useful in determining the pathology and appropriate treatment for compressive neuropathies. In this study, a rare accessory muscle has been described.
Pancreatic islets are responsible for blood glucose homeostasis. Reduced numbers of functional (insulin-secreting) beta-cells in pancreatic islets underlies diabetes. Restoration of the secretion of the proper amount of insulin is a goal. Beta-cell mass is increased by neogenesis, proliferation and cell hypertrophy, and is decreased by beta-cell death primarily through apoptosis. Many hormones and nutrients affect beta-cell mass, and glucose and free fatty acid are thought to be the most important determinants of beta-cell equilibrium. A number of molecular pathways have been implicated in beta-cell mass regulation and have been studied. This review will focus on the role of the principle metabolites, glucose and free fatty acid, and the downstream signaling pathways regulating beta-cell mass by these metabolites.
We examined morphological differences between the sublingual and submandibular glands with special reference to their innervation. The sublingual gland contained abundant periodic acid Schiff-positive mucous acini: some lobules were composed of purely mucous acini, while others were purely serous or mixed. However, in the submandibular gland, the area of mucous acini was very limited. Notably, in the sublingual gland, immunohistochemistry for neuron-specific enolase demonstrated that the serous acini carried a higher density of nerve elements than the mucous acini. However, no such difference was evident in the submandibular gland, possibly due to the small areas of the mucous acini. In both types of gland, neuronal nitric oxide synthase-positive parasympathetic nerves as well as tyrosine hydroxylase-positive sympathetic nerves were observed in the interlobular tissue, but we were unable to trace these thin fibers to the acini. Myoepithelial cells expressed smooth muscle actin, but were negative for S100B protein, glial fibrillary acidic protein and neuron-specific enolase. However, antibody against S100A stained some of the myoepithelial cells and ductal cells in the sublingual gland. Cells positive for peripheral myelin protein 22 were seen in some of the ductal cells in the submandibular gland, but not in the sublingual gland. Therefore, with regard to the neurogenic features of the gland cells, S100B reactivity might disappear first in postnatal life, whereas S100A reactivity is likely to remain as aging progresses. The sublingual gland in elderly individuals seems to provide a good model for comparison of the nerve supply between mucous and serous acini.
Instrumental role of Na(+) and Ca(2+) influx via Na(+)/K(+) adenosine triphosphatase (Na(+)/K(+)-ATPase) and Na(+)/Ca(2+) exchanger 1 (NCX1) is examined in the N-Methyl-D-aspartate (NMDA) receptor-mediated pathogenesis of penumbra after focal cerebral ischemia. An experimental model of 3, 6, and 24 h focal cerebral ischemia by permanent occlusion of middle cerebral artery was developed in rats. The changes in protein expression of Na(+)/K(+)-ATPase and NCX1 as well as functional subunits of NMDA receptor 2A and 2B (NR2A and NR2B) in the penumbra were assessed using by quantitative immunoblottings. The most prominent changes of Na(+)/K(+)-ATPase (78±6%, n=4, (*)P<0.05) and NCX1 (144±2%, n=4, (*)P<0.05) in the penumbra were developed 24 h after focal cerebral ischemia. The expression of NR2A in the penumbra was significantly increased (153±9%, n=4, (*)P<0.05) whereas the expression of NR2B was significantly decreased (37±2%, n=4, (*)P<0.05) as compared with sham-operated controls 3 h after focal cerebral ischemia. However, the expression of NR2A and NR2B in the penumbra was reversed 24 h after focal cerebral ischemia (NR2A: 40±7%; NR2B: 120±16%, n=4, (*)P<0.05). Moreover, the decreased expression of neuronal nuclei (NeuN) in the penumbra was most prominent than that of glial fibrillary acidic protein (GFAP) 24 h after focal cerebral ischemia. These findings imply that intracellular Na(+) accumulation via decreased Na(+)/K(+)-ATPase exacerbate the Ca(2+) overload cooperated by the increased NCX1 and NR2B-containing NMDA receptor which may play an important role in the pathogenesis of the penumbra.
Among the several rotenoids, amorphigenin is isolated from the leaves of Amopha Fruticosa and it is known that has anti-proliferative effects and anti-cnacer effects in many cell types. The main aim of this study was to investigate the effects of amorphigenin on osteoclast differentiation in vitro and on LPS treated inflammatory bone loss model in vivo. We show here that amorphigenin inhibited RANKL-induced osteoclast differentiation from bone marrow macrophages in a dose dependent manner without cellular toxicity. Anti-osteoclastogenic properties of amorphigenin were based on a down-regulation of c-fos and NFATc1. Amorphigenin markedly inhibited RANKL-induced p38 and NF-κB pathways, but other pathways were not affected. Micro-CT analysis of the femurs showed that amorphigenin protected the LPS-induced bone loss. We concluded that amorphigenin can prevent inflammation-induced bone loss. Thus we expect that amorphigenin could be a treatment option for bone erosion caused by inflammation.
A holy grail of curing neurodegenerative diseases is to identify the main causes and mechanisms underlying neuronal death. Many studies have sought to identify these targets in a wide variety of ways, but a more important task is to identify critical molecular targets and their origins. Potential molecular targets include advanced glycation end products (AGEs) that can promote neuronal cell death, thereby contributing to neurodegenerative disorders such as Alzheimer disease or Parkinson disease. In this study, we showed that AGE-albumin (glycated albumin) is synthesized in microglial cells and secreted in the human brain. Our results provide new insight into which microglial cells can promote the receptor for AGE-mediated neuronal cell death, eventually leading to neurodegenerative diseases.
Activating transcription factor 3 (ATF3) and c-Jun play key roles in either cell death or cell survival, depending on the cellular background. To evaluate the functional significance of ATF3/c-Jun in the peripheral nervous system, we examined neuronal cell death, activation of ATF3/c-Jun, and microglial responses in facial motor nuclei up to 24 weeks after an extracranial facial nerve axotomy in adult rats. Following the axotomy, neuronal survival rate was progressively but significantly reduced to 79.1% at 16 weeks post-lesion (wpl) and to 65.2% at 24 wpl. ATF3 and phosphorylated c-Jun (pc-Jun) were detected in the majority of ipsilateral facial motoneurons with normal size and morphology during the early stage of degeneration (1-2 wpl). Thereafter, the number of facial motoneurons decreased gradually, and both ATF3 and pc-Jun were identified in degenerating neurons only. ATF3 and pc-Jun were co-localized in most cases. Additionally, a large number of activated microglia, recognized by OX6 (rat MHC II marker) and ED1 (phagocytic marker), gathered in the ipsilateral facial motor nuclei. Importantly, numerous OX6- and ED1-positive, phagocytic microglia closely surrounded and ingested pc-Jun-positive, degenerating neurons. Taken together, our results indicate that long-lasting co-localization of ATF3 and pc-Jun in axotomized facial motoneurons may be related to degenerative cascades provoked by an extracranial facial nerve axotomy.
Spatially and temporally programmed expression of the Hox genes along the antero-posterior (A-P) axis is essential for correct pattern formation during embryonic development. An accumulating body of evidence indicates the pivotal role of spatial chromatin organization for the coordination of gene regulation. Recently, chromosome conformation capture (3C) technique has been developed and opened a new way to study chromosomal interactions in the nucleus. In this study, we describe 3C method we applied in F9 embryonic teratocarcinoma cells and demonstrate that the chromosomal interactions at Hox loci are successfully detected. Interestingly, at Hoxc loci, the abundance of intrachromosomal interactions with neighboring fragments was drastically decreased when the genes are expressed. These results indicate the possibility of the dynamic pattern of chromosomal interaction in association with the transcriptional regulation of Hox genes.
Treatment with cisplatin for cancer therapy has a major side effect such as nephrotoxicity; however, the role of poly (ADP-ribose) polymerase 1 (PARP1) in necrosis in response to cisplatin nephrotoxicity remains to be defined. Here we report that cisplatin induces primary necrosis through PARP1 activation in kidney proximal tubular cells derived from human, pig and mouse. Treatment with high dose of cisplatin for 4 and 8 hours induced primary necrosis, as represented by the percentage of propidium iodide-positive cells and lactate dehydrogenase release. The primary necrosis was correlated with PARP1 activation during cisplatin injury. Treatment with PJ34, a potent PARP1 inhibitor, at 2 hours after injury attenuated primary necrosis after 8 hours of cisplatin injury as well as PARP1 activation. PARP1 inhibition also reduced the release of lactate dehydrogenase and high mobility group box protein 1 from kidney proximal tubular cells at 8 hours after cisplatin injury. Oxidative stress was increased by treatment with cisplatin for 8 hours as shown by 8-hydroxy-2'-deoxyguanosine and lipid hydroperoxide assays, but PARP1 inhibition at 2 hours after injury reduced the oxidative damage. These data demonstrate that cisplatin-induced PARP1 activation contributes to primary necrosis through oxidative stress in kidney proximal tubular cells, resulting in the induction of cisplatin nephrotoxicity and inflammation.
Myelinated Schwann cells in the peripheral nervous system express the p75 nerve growth factor receptor (p75NGFR) as a consequence of Schwann cell dedifferentiation during Wallerian degeneration. p75NGFR has been implicated in the remyelination of regenerating nerves. Although many studies have shown various mechanisms underlying Schwann cell dedifferentiation, the molecular mechanism contributing to the re-expression of p75NGFR in differentiated Schwann cells is largely unknown. In the present study, we found that lysosomes were transiently activated in Schwann cells after nerve injury and that the inhibition of lysosomal activation by chloroquine or lysosomal acidification inhibitors prevented p75NGFR expression at the mRNA transcriptional level in an ex vivo Wallerian degeneration model. Lysosomal acidification inhibitors suppressed demyelination, but not axonal degeneration, thereby suggesting that demyelination mediated by lysosomes may be an important signal for inducing p75NGFR expression. Tumor necrosis factor-α (TNF-α) has been suggested to be involved in regulating p75NGFR expression in Schwann cells. In this study, we found that removing TNF-α in vivo did not significantly suppress the induction of both lysosomes and p75NGFR. Thus, these findings suggest that lysosomal activation is tightly correlated with the induction of p75NGFR in demyelinating Schwann cells during Wallerian degeneration.
Atherosclerosis is readily observed in areas where disturbed flow is formed, while the atheroprotective region is found in areas with steady laminar flow (L-flow). It has been established that L-flow protects endothelial cells against endothelial dysfunction, including apoptosis and inflammation. It has also been reported that extracellular signal-regulated kinase 5 (ERK5) regulated endothelial integrity and protected endothelial cells from vascular dysfunction and disease under L-flow. However, the molecular mechanism by which L-flow-induced ERK5 activation inhibits endothelial apoptosis has not yet been determined. Transcription factor p53 is a major pro-apoptotic factor which contributes to apoptosis in various cell types. In this study, we found that 15-deoxy-Δ(12,14)-prostaglandin J(2) induced p53 expression and that endothelial apoptosis was reduced under the L-flow condition. This anti-apoptotic response was reversed by the biochemical inhibition of ERK5 activation. It was also found that activation of ERK5 protected endothelial apoptosis in a C terminus of Hsc70-interacting protein (CHIP) ubiquitin ligase-dependent manner. Moreover, molecular interaction between ERK5-CHIP and p53 ubiquitination were addressed with a CHIP ubiquitin ligase activity assay. Taken together, our data suggest that the ERK5-CHIP signal module elicited by L-flow plays an important role in the anti-apoptotic mechanism in endothelial cells.
Vitamin C, one of essential micronutrients, has been reported to modulate the humoral immune responses in some mammals. We investigated whether vitamin C might modulate this response in mice by directly affecting B cells. Splenic B cells were isolated and activated by CD40- and B cell receptor-ligation in vitro. The cells were cultured with a pretreatment of vitamin C from 0 to 1 mM of concentrations. Vitamin C slightly increased apoptosis of B cells dose-dependently and behaved as an antioxidant. We found that in vivo administration of vitamin C by intraperitoneal injection affected isotype switching as previously reported: the titer of antigen-specific IgG1 antibody was decreased, while that of IgG2a was unaffected. Somewhat different from those observed in vivo, in vitro exposure to vitamin C slightly decreased isotype switching to IgG1 and increased isotype switching to IgG2a. Pretreatment with vitamin C in the safe range did not affect either proliferation of cultured B cells or the expression of CD80 and CD86 in those cells. Taken together, in vivo results suggest that vitamin C acts to modulate isotype switching in the mouse. However, because of our in vitro results, we suggest that the modulation exerted by vitamin C in vivo is by indirectly affecting B cells, perhaps by directly influencing other immune cells such as dendritic cells.
Selective labeling of small populations of neurons of a given phenotype for conventional neuronal tracing is difficult because tracers can be taken up by all neurons at the injection site, resulting in nonspecific labeling of unrelated pathways. To overcome these problems, genetic approaches have been developed that introduce tracer proteins as transgenes under the control of cell-type-specific promoter elements for visualization of specific neuronal pathways. The aim of this study was to explore the use of tracer gene expression for neuroanatomical tracing to chart the complex interconnections of the central nervous system. Genetic tracing methods allow for expression of tracer molecules using cell-type-specific promoters to facilitate neuronal tracing. In this study, the rat tyrosine hydroxylase (TH) promoter and an adenoviral delivery system were used to express tracers specifically in dopaminergic and noradrenergic neurons. Region-specific expression of the transgenes was then analyzed. Initially, we characterized cell-type-specific expression of GFP or RFP in cultured cell lines. We then injected an adenovirus carrying the tracer transgene into several brain regions using a stereotaxic apparatus. Three days after injection, strong GFP expression was observed in the injected site of the brain. RFP and WGA were expressed in a cell-type-specific manner in the cerebellum, locus coeruleus, and ventral tegmental regions. Our results demonstrate that selective tracing of catecholaminergic neuronal circuits is possible in the rat brain using the TH promoter and adenoviral expression.
Stress has long been known to be a causative factor of various disease states. In this study, we investigated the effects of repeated restraint stress on platelet endothelial cell adhesion molecule-1 (PECAM-1), a very important mediator in inflammation, immunoreactivity and protein levels as well as neuronal damage, in the gerbil hippocampus after 5 minutes of transient cerebral ischemia. Transient ischemia-induced neuronal death was shown in CA1 pyramidal cells 4 days after ischemia/reperfusion. However, repeated restraint stress protected neuronal death induced by ischemic damage. In the ischemia-group, PECAM-1 immunoreactivity and its protein levels were significantly increased in all the hippocampal subregions 4 days after ischemia/reperfusion. However, PECAM-1 immunoreactivity and its protein levels did not change significantly in the hippocampus of the stress-ischemia-group compared to the sham-groups. These results indicate that repeated restraint stress protects neuronal damage induced by transient cerebral ischemia, and this may be associated with maintenance of PECAM-1levels.
Adiponectin is an adipocytokine released by the adipose tissue and has multiple roles in the immune system and in the metabolic syndromes such as cardiovascular disease, Type 2 diabetes, obesity and also in the neurodegenerative disorders including Alzheimer's disease. Adiponectin regulates the sensitivity of insulin, fatty acid catabolism, glucose homeostasis and anti-inflammatory system through various mechanisms. Previous studies demonstrated that adiponectin modulates memory and cognitive impairment and contributes to the deregulated glucose metabolism and mitochondrial dysfunction observed in Alzheimer's disease. Here, we aim to summarize recent studies that suggest the potential correlation between adiponectin and Alzheimer's disease.
Mesenchymal stem cells (MSCs) of human origin have been frequently applied to experimental animal models to evaluate their immunomodulatory functions. MSCs are known to be activated by cytokines from T cells, predominantly by interferon-γ (IFN-γ), in conjunction with other cytokines such as tumor necrosis factor-α (TNF-α) and interlukin-1β. Because IFN-γ is not cross-reactive between human and mouse species, the manner in which human MSCs administered in experimental animals are activated and stimulated to function has been questioned. In the present study, we established MSCs from human adipose tissue. They successfully suppressed the proliferation of not only human peripheral blood mononuclear cells but also mouse splenic T cells. When these human MSCs were stimulated with a culture supernatant of mouse T cells or recombinant murine TNF-α, they expressed cyclooxygenase-2 (COX-2), but not indoleamine 2,3-dioxygenase. The dominant role of COX-2 in suppressing mouse T cell proliferation was validated by the addition of COX-2 inhibitor in the co-culture, wherein the suppressed proliferation was almost completely recovered. In conclusion, human MSCs in a murine environment were activated, at least in part, by TNF-α and mainly used COX-2 as a tool for the suppression of in vitro T cell proliferation. These results should be considered when interpreting results for human MSCs in experimental animals.
Using immunohistochemical staining for alpha-smooth muscle actin (α-SMA), glial fibrillary acidic protein (GFAP), S100 protein (S100), p63, cytokeratin 14 (CK14), and cytokeratin 19 (CK19), we studied acinar and myoepithelial cells of major and minor salivary glands obtained from 14 donated cadavers (78-92 years old) and 5 donated fetuses (aborted at 15-16 weeks of gestation). CK and p63 expression was investigated only in the adult specimens. SMA was detected in all adult glands as well as in fetal sublingual and pharyngeal glands. GFAP expression was seen in a limited number of cells in adult glands, but was highly expressed in fetal pharyngeal glands. S100-positive myoepithelial-like cells were present in adult minor glands as well as in fetal sublingual and pharyngeal glands. Expression of p63 was evident in the ducts of adult glands. CK14 immunoreactivity was observed in a limited number of glandular cells in adults, in contrast to consistent expression of CK19. In both adults and fetuses, a mosaic expression pattern was usually evident for each of the examined proteins. A difference in immunoreactivity for the nerve markers GFAP and S100 was observed between the major and minor glands. Thus, in the present histologic study, we distinguished between the specific gland types on the basis of their immunohistochemical staining. A mosaic expression pattern suggested that the immunoreactivity against nerve protein markers in myoepithelial cells could not be due to the persistence of neural crest remnants or the physiological status of the gland, such as age-related degeneration.
The occurrence of a brachial plexus united into a single cord is very rare. During routine dissection of an elderly female cadaver, the brachial plexus united into a single cord was observed bilaterally. On the left side, C4, C5, and C6 roots combined to form the upper trunk, the C7 root continued as the middle trunk, and C8 and T1 united to form the lower trunk. All three trunks almost immediately fused to form a single cord. On the right side, C5 and C6 roots joined to form the upper trunk, which divided into anterior and posterior divisions. C7, C8, and T1 roots combined to form the lower trunk. The anterior and posterior divisions united with the lower trunk to form a single cord. On both sides, the subclavian artery was superior to the single cord. Supraclavicular brachial plexus injuries in such individuals may have serious clinical manifestations.
Ultrastructural parameters related to synaptic release and their correlation with synaptic connectivity were analyzed in the low-threshold mechanoreceptive vibrissa afferent boutons in laminae III and IV of the trigeminal caudal nucleus (Vc). Rapidly adapting vibrissa afferents were intra-axonally labeled, and quantitative ultrastructural analyses with serial sections were performed on the labeled boutons and their presynaptic endings (p-endings). The volume of the labeled boutons was widely distributed from small to large ones (0.8~12.3 µm(3)), whereas the p-endings were small and uniform in size. The volume of the labeled boutons was positively correlated with the ultrastructural parameters such as mitochondrial volume (correlation coefficient, r=0.96), active zone area (r=0.82) and apposed surface area (r=0.79). Vesicle density (r=-0.18) showed little correlation to the volume of labeled boutons, suggesting that the total vesicle number of a bouton is proportional to its volume. In addition, the bouton volume was positively correlated with the number of p-endings (r=0.52) and with the number of dendrites postsynaptic to the labeled bouton (r=0.83). These findings suggest that low-threshold mechanoreception conveyed through vibrissa afferents is processed in a bouton size-dependent manner in the Vc, which may contribute to the sensory-motor function of laminae III/IV in Vc.
Previously, anatomists considered paranasal sinuses as a mysterious region of the human skull. Historically, paranasal sinuses were first identified by ancient Egyptians and later, by Greek physicians. After a long period of no remarkable improvement in the understanding of anatomy during the Middle Ages, anatomists of the Renaissance period-Leonardo da Vinci and Vesalius-made their own contribution. Nathaniel Highmore's name is also associated with the anatomy of paranasal sinuses as he was first to describe the maxillary sinus.
Nitric oxide (NO) production by endothelial nitric oxide synthase (eNOS) plays a protective role in cerebral ischemia by maintaining vascular permeability, whereas NO derived from neuronal and inducible NOS is neurotoxic and can participate in neuronal damage occurring in ischemia. Matrix metalloproteinases (MMPs) are up-regulated by ischemic injury and degrade the basement membrane if brain vessels to promote cell death and tissue injury. We previously reported that agmatine, synthesized from L-arginine by arginine decarboxylase (ADC) which is expressed in endothelial cells, has shown a direct increased eNOS expression and decreased MMPs expression in bEnd3 cells. But, there are few reports about the regulation of eNOS by agmatine in ischemic animal model. In the present study, we examined the expression of eNOS and MMPs by agmatine treatment after transient global ischemia in vivo. Global ischemia was induced with four vessel occlusion (4-VO) and agmatine (100 mg/kg) was administered intraperitoneally at the onset of reperfusion. The animals were euthanized at 6 and 24 hours after global ischemia and prepared for other analysis. Global ischemia led severe neuronal damage in the rat hippocampus and cerebral cortex, but agmatine treatment protected neurons from ischemic injury. Moreover, the level and expression of eNOS was increased by agmatine treatment, whereas inducible NOS (iNOS) and MMP-9 protein expressions were decreased in the brain. These results suggest that agmatine protects microvessels in the brain by activation eNOS as well as reduces extracellular matrix degradation during the early phase of ischemic insult.
Stroke or cerebrovascular injury is the leading cause of disability and the third leading cause of deaths worldwide. After the initial ischemic injury, sympathetic signals are transmitted to the spleen and a compromised blood-brain barrier, coupled with expression of adhesion molecules by the vascular endothelial cells permits an influx of peripheral immune cells. This influx of peripheral immune cells into the brain exacerbates the local brain inflammatory response, leading to enhanced neurodegeneration. Agmatine is a primary amine formed by decarboxylation of L-arginine synthesized in the mammalian brain. In this study, we determined the effect of agmatine on the immune response in the spleen after transient cerebral ischemia. Twenty-three hours after transient cerebral ischemia, the white pulp area was reduced and the number of CD11b(+) macrophages and CD4(+)CD25(+) regulatory T cells (T reg cells) were increased in the spleens in the experimental group as a result of alteration of the immune response in the spleen, as regulated by inflammatory cytokines. In the agmatine treatment group (100 mg/kg IP), the contraction of white pulp was diminished and the number of CD11b(+) macrophages and CD4(+)CD25(+)T reg cells were decreased. Twenty-three hours after transient cerebral ischemia, the brain infarction area was significantly reduced (5.51±1.63% of the whole brain) in the agmatine treatment group compared to 15.02±4.28% of the whole brain in the experimental control group. These results suggest that agmatine treatment can reduce brain infarction through minimizing neuroinflammation and can lessen the danger of post-stroke infection from depression of the immune system after stroke.
Cannabinoids have been proposed to possess neuroprotective properties; though their mechanism of action remains contentious, they are posited to prevent neurodegenerative disorders, including Parkinson's disease, the pathogenesis of which has not been established. Recent studies have demonstrated that induction of proteasomal dysfunction in animal models results in a phenotype similar to Parkinson's disease. Here, we investigated the neuroprotective function of a synthetic cannabinoid-receptor agonist (WIN55.212.2) in dopaminergic neuronal death induced by a proteasomal synthase inhibitor (PSI), additionally testing the hypothesis that WIN55.212.2 modulates cytoplasmic accumulation of parkin and α-synuclein, a key feature of proteasomal dysfunction in Parkinson's. WIN55.212.2 protects PC12 cells from PSI-induced cytotoxicity, concomitantly inhibiting PSI-induced polyADP ribose polymerase expression and activation of caspase-3. While PSI induces cytoplasmic accumulation of α-synuclein and parkin, WIN55.212.2 counters these effects. Interestingly, however, while PSI induces the activation and nuclear translocalization of nuclear factor κB, WIN55.212.2 potentiates this effect. These data are suggestive that WIN55.212.2 might confer a neuroprotective benefit in PSI-induced proteasomal dysfunction, and could further protect against neuronal degeneration stemming from cytoplasmic accumulation of α-synuclein and parkin. These results indicate that WIN55.212.2 may be a candidate for treatment of neurodegenerative diseases, including Parkinson's disease.
Stem cell research has been widely studied over the last few years and has attracted increasing attention from researchers in all fields of medicine due to its potential to treat many previously incurable diseases by replacing damaged cells or tissues. As illustrated by hematopoietic stem research, understanding stem cell differentiation at molecular levels is essential for both basic research and for clinical applications of stem cells. Although multiple integrative analyses, such as genomics, epigenomics, transcriptomics and proteomics, are required to understand stem cell biology, proteomics has a unique position in stem cell research. For example, several major breakthroughs in HSC research were due to the identification of proteins such as colony-stimulating factors (CSFs) and cell-surface CD molecules. In 2007, the Human Proteome Organization (HUPO) and the International Society for Stem Cell Research (ISSCR) launched the joint Proteome Biology of Stem Cells Initiative. A systematic proteomics approach to understanding stem cell differentiation will shed new light on stem cell biology and accelerate clinical applications of stem cells.
The present study examined the efficacy of Ocimum basilicum (basil) extract, a natural herb, with antioxidant properties, against testicular toxicity induced by cadmium (Cd), which is one of the most important toxic heavy metals. The intoxicated rats showed significant alterations in the testicular tissue including decreased seminiferous epithelium height and changes in the arrangement of spermatogenic layers. Hypospermatogensis with cytoplasmic vacuolization and pyknotic nuclei were observed. Intertubular hemorrahage and absence of spermatozoa were noted. Decreased cell proliferation was reflected by a decrease in Ki-67 expression, whereas the increase in apoptotic rate was associated with a decrease in the Bcl/Bax ratio. Concomitant treatment with aqueous basil extract led to an improvement in histological, morphometrical and immunohistochemical changes induced by Cd. The beneficial effects of basil extract could be attributed to its antioxidant properties.
Using computerized tomographic data and three dimensional model, we studied the influence of tibial intramedullary canal axis and other morphologic factors of the tibia on the entry point for tibial intramedullary alignment guides. Various anatomical parameters including tibial anteroposterior dimensions (AP), mediolateral dimensions (ML), aspect ratio (ML/AP), bowing and the intramedullary canal axis were studied. In addition, the entry point for the intramedullary alignment guide for primary and revision total knee arthroplasty were studied. The averaged entry point at the level of the tibial plateau was 5.7±2.2 mm anterior and 4.3±2.0 mm lateral to the classical entry point (P<.001). Furthermore, this entry point was more anterolateral in females when compared to males (P<.001). At a depth 10 mm below the tibial plateau, the entry point was on average 8.8±1.9 mm anterior and 2.9±1.9 mm lateral to the center of the cut surface. With increasing tibial varus the entry point tended to shift laterally at both levels (r=0.49) (P<.001). In Korean, the entry point for tibial intramedullary alignment systems is anterolateral to the classically described entry point. Moreover, the increment of tibial varus necessitates more lateral placement of the entry point. Intraoperatively, the entry point can be localized during primary knee arthroplasty to a point 15.9±2.8 mm anterior to and 1.2±2.8 mm lateral to the lateral tibial spine. For revision knee arthroplasty the point is on average 8.8±1.9 mm anterior and 2.9±1.9 mm lateral to the center of the cut surface of the tibia at a depth of 10 mm from the articular surface.