The arterial pressure is regulated by the nervous and humoral mechanisms. The neuronal regulation is mostly carried out by the autonomic nervous system through the rostral ventrolateral medulla (RVLM), a key area for the cardiovascular regulation, and the humoral regulation is mediated by a number of substances, including the angiotensin (Ang) II and vasopressin. Recent studies suggest that central interleukin-1 (IL-1) activates the sympathetic nervous system and produces hypertension. The present study was undertaken to elucidate whether IL-1 and Ang II interact in the regulation of cardiovascular responses to the stress of hemorrhage. Thus, Sprague-Dawley rats were anesthetized and both femoral arteries were cannulated for direct measurement of arterial pressure and heart rate (HR) and for inducing hemorrhage. A guide cannula was placed into the lateral ventricle for injection of IL-1 $(0.1,\;1,\;10,\;20\;ng/2\;{\mu}l)$ or Ang II $(600\;ng/10\;{\mu}l)$. A glass microelectrode was inserted into the RVLM to record the single unit spike potential. Barosensitive neurons were identified by an increased number of single unit spikes in RVLM following intravenous injection of nitroprusside. I.c.v. $IL-1\;{\beta}$ increased mean arterial pressure (MAP) in a dose-dependent fashion, but HR in a dose-independent pattern. The baroreceptor reflex sensitivity was not affected by i.c.v. $IL-1\;{\beta}$. Both i.c.v. $IL-1\;{\alpha}\;and\;{\beta}$ produced similar increase in MAP and HR. When hemorrhage was induced after i.c.v. injection of $IL-1\;{\beta}$, the magnitude of MAP fall was not different from the control. The $IL-1\;{\beta}$ group showed a smaller decrease in HR and a lower spike potential count in RVLM than the control. MAP fall in response to hemorrhage after i.c.v. injection of Ang II was not different from the control. When both IL-1 and Ang II were simultaneously injected i.c.v., however, MAP fall was significantly smaller than the control, and HR was increased rather than decreased. These data suggest that IL-1, a defense immune mediator, manifests a hypertensive action in the central nervous system and attenuates the hypotensive response to hemorrhage by interaction with Ang II.
Khalaf, Abd EI-Azeim A.;Morgan, Ashraf M.;Mekawy, Mohey M.;Ali, Maged F.
Toxicological Research
/
제24권1호
/
pp.51-58
/
2008
The present study was designed to explore the immunotoxic effects of orally administered aluminum (AI) on pregnant rats (n = 60) and their growing fetuses and consequently on the animal wealth. The animals were randomly allocated into three equal groups of 20 rats each. The first group has no treatment and kept as a control (G1). The second and third groups of pregnant rats were treated orally with aluminum chloride at 345 mg/Kg b.wt. The second group (G2) received the tested compound from the $6^{th}$ day of gestation to the end of weaning, whereas the third group (G3) received the tested compound from the $15^{th}$h day of gestation to the end of weaning. Control and treated animals (dams and offspring) were immunized ip with (0.5 ml) 20% sheep red blood cell (SRBC) suspension seven days before the end of experiments. At the end of exposure, ten dams and ten offspring from each group were used for assessment of cell-mediated immunity and a similar number of animals were sacrificed for evaluating the humoral immune response and serum protein profile. Aluminum chloride exposure of dams ($G_2&G_3$) caused significant suppression of both cell mediated and humoral immune responses in the obtained offsprings compared to the control group ($G_1$) without any significant effect on the immune responses of these dams. Moreover, the serum total globulins, albumin/ globulin (A/G) ratio and gamma globulin fraction were significantly decreased in the treated dam's offsprings compared to the corresponding controls while the serum total protein and all serum protein fractions showed non significant difference between the control and treated dams and between the two treated dam groups themselves. There were no histopathological changes observed in thymus, spleen and liver of the control and treated dams. Thymus of treated dam's offsprings (G2) showed lymphoid depletion in both cortex and medulla. Their spleens showed lymphoid depletion in the white pulps and congestion with hemosiderosis in the red pulps. Liver of treated dam's offsprings showed dilation and congestion of its central vein with degenerative changes in the hepatocytes. These histopathological changes were more severe in G2 than in G3 offsprings. It can be concluded that gestational and/ or lactation exposure of pregnant dams to AI chloride caused suppression of both cellular and humoral immune responses of their offsprings.
The only compounds with antagonistic activity via AT$_1$receptor, one of two subtypes of angiotensin II (AII) receptor, have been demonstrated to block the vasoconstriction effects of AII and thereby provide therapeutic potential. This initiated the search for compounds with high specific affinity to AT$_1$receptor and their effective screening methods. The radioligand binding assay for the AII receptor is regarded as the primary method for the evaluation of AT$_1$receptor antagonists for their activity. In this paper, we characterized the liver AT$_1$receptor and describe the efficient method of the radioligand binding assay using rat liver as a source of AT$_1$receptor. Equilibrium binding studies with rat adrenal cortex, adrenal medulla, liver and bovine adrenal showed that the specific bindings of [$^3$H] AII were saturable in all tissues and the Scatchard plots of those data were linear, suggesting a single population of binding sites. Hill slopes were very near to the unity in all tissues. Kinetic studies of [$^3$H) AII binding in rat liver homogenates yielded two association rate constants, 4.10$\times$10$^{7}$ M$^{-1}$ min$^{-1}$ and 4.02$\times$10$^{9}$ M$^{-1}$ min$^{-1}$ , with a single dissociation rate constant, 7.07$\times$10$^{-3}$ min-$^{-1}$ , possibly due to the partial dissociation phenomenon. The rank order of inhibition potencies of [$^3$H] AII binding in rat liver was AII>Sarile>Losartan>PD 123177. Rat liver homogenates revealed to have very high density of homogeneous population of the AT$_1$receptor subtype, as the specifically bound [$^3$H] AII was not inhibited by PD 123177, the nonpeptide antagonist of AT$_2$. The results of this study demonstrated that the liver homogenates from rats could be the best receptor preparation for the AT$_1$receptor binding assay and provide an efficient system for the screening of newly synthesized candidate compounds of AT$_1$receptor antagonist.
This study is aimed to report two cases of chronic kidney disease treated with Korean traditional medicine. We treated the patients with traditional herbal medicine and other treatments including acupuncture. We measured serum creatinine, estimated glomerular filtration rate(eGFR), blood urea nitrogen(BUN), albumin, red blood cell count(RBC), hemoglobin for several times during admission. Case 1 patient was diagnosed with right medulla infarction, bladder stone, chronic kidney disease. The symptoms were quadriplegia, right side dysesthesia, drowsiness and edema. Case 2 patient was diagnosed with acute cerebral infarction, hypertension, chronic kidney disease. The symptoms were right side weakness, delusion, anorexia, low back pain. Case 1 patient was hospitalized for 80 days, and case 2 patient was for 31 days. Korean traditional medicine decreased serum creatinine and BUN level, improved eGFR, increased RBC and hemoglobin. The symptoms of chronic kidney disease such as edema, general body weakness and anorexia were also improved. These cases suggest that Korean traditional medicine can be effective and safe for patients with chronic kidney disease.
Objective : Aneurysms of vertebral artery and its branches make up approximately 3% of all intracranial aneurysms. As the aneurysm have an intimate relationship with lower cranial nerves and medulla, surgical management of the aneurysms are one of the challenging neurosurgical problems. The authors analyzed the management outcomes for aneurysms arising from vertebral artery and its branches. Methods : At the authors' institution between May 1989 and Jan. 2000, 42 patients were treated with transcranial and endovascular surgery for aneurysms of vertebral artery and its branches. The medical records and neuroimaging studies of the patients were reviewed retrospectively. Results : Forty two patients were comprised of 28 female and 14 male patients aged from 26-80 year old(mean : 51.8). Of the 42 patients, 37 patients(88%) had subarachnoid hemorrhage. Of the 37 patients with subarachnoid hemorrahge, 35 patients(95%) were in good neurological status(Hunt Hess grade I-III), 2 patients(5%) in poor grade(H-H grade IV-V) before operation. Location of the aneurysm were 16 in vertebral artery, 12 in vertebro-PICA junction, and 14 in the peripheral PICA. Twenty nine patients were treated with transcranial surgery and 13 patients with endovascular surgery. The management outcome of the transcranial surgery was : Glasgow outcome scale(GOS) I and II ; 24, GOS III ; 2, GOS IV ; 1 and GOS V(death) ; 2. The causes of mortality related to transcranial surgery were rebleeding after failure in clipping in one and suspected brainstem infarct in one. Morbidity was attributed to vasospasm(3), lower CN palsy(7, including temporary dysfunction) and pseudomeningocele(1). The management outcome of the endovascular surgery was : Glasgow outcome scale(GOS) I-II ; 9, GOS III ; 1, GOS IV ; 1, and GOS V(death) ; 2. The causes of mortality related to endovascular surgery were sepsis from pneumonia(1) and vasospasm(1). There were one cerebellar infarct and one lateral medullary syndrome. Conclusion : Excellent and good surgical results can be expected in 80% of the patients with aneurysms of vertebral arery and its branches. The outcomes of endovascular surgery in treating vertebral artery aneurysm were satisfactory and endovascular surgery may offer a therapeutic alternative especially in vertebral dissecting aneurysm.
It is well known that chromaffin cells of adrenal medulla secrete catecholamine in response to sympathetic nerve activation and the influx of $Ca^{2+}$ through the voltage dependent $Ca^{2+}$ channels (VDCC) in the cell membrane do a major role in this secretory process. In this study, we explored the effect of divalent cations on VDCC of rat chromaffin cells. Rat (Sprague-Dawley rat, 150-250 gm) chromaffin cells were isolated and cultured. Standard giga seal, whole cell recording techniques were employed to study $Ca^{2+}$ current with external and internal solutions that could effectively isolate VDCC currents $(NMG\;in\;external\;and\;TEA\;and\;Cs^{2+}\;in\;internal\;solution)$. The voltage dependence and the inactivation time course of VDCC in our cells were identical to those of bovine chromaffin cells. A persistent inward current was first activated by depolarizing step pulse from the holding potential (H.P.) of -80 mV to -40 mV, increased to maximum amplitude at around +10 mV, and became smaller with progressively higher depolarizing pulses to reverse at around +60 mV. The inactivation time constant $(\tau)$, fitted from the long duration test potential (2 sec) was $1295.2{\pm}126.8$ msec $(n=20,\;1\;day\;of\;culture,\;mean\;{\pm}S.E.M.)$ and the kinetic parameters were not altered along the culture duration. Nicardipine $(10\;{\mu}M)$ blocked the current almost completely. Among treated divalent cations such as $Cd^{2+},\;Co^{2+},\;Ni^{2+},\;Zn^{2+}\;and\;,Mn^{2+},\;Cd^{2+}$ was the most potent blocker on VDCC. When the depolarizing step pulse from -80 mV to 10 mV was applied, the equilibrium dissociation constant $(K_d)$ of $Cd^{2+}\;was\;39\;{\mu}M,\;K_d\;of\;Co^{2+}\;was\;100\;{\mu}M\;and\;K_d\;of\;Ni^{2+}];was];780{\mu}M.$ The principal findings of this study are as follows. First, the majority of $Ca^{2+}$ channels in rat chromaffin cells are well classified to L-type $Ca^{2+}$ channel in the view of kinetics and pharmacology. Second, all divalent cations tested could block the $Ca^{2+}$ current and the most potent blocker among the tested was $Cd^{2+}$.
Gentamicin (GM) is a polybasic, aminoglycoside antibiotic used frequently for the treatment of serious gram-negative infections. The major limiting factors in the clinical use of GM as well as other aminoglycoside antibiotics are their nephrotoxicity and ototoxicity. The primary mechanism of cell injury in aminoglycoside toxicity appears to be the disruption of normal membrane function and the inhibition of $Na^{+}-K^{+}$ ATPase activity. There are both indirect and direct evidences which suggests that the effect of aminoglycoside antibiotics on $Na^{+}-K^{+}$ ATPase may explain, or contribute to, their toxicity. It has been shown that aminoglycoside reduce total ATPase activity (Kaku et al., 1973) and $Na^{+}-K^{+}$ ATPase activity (linuma et al., 1967) in the stria vascularis and spiral ligament of the guinea-pig cochlea. Lipsky and Lietman (1980) reported that aminoglycoside antibitoics inhibited the activity of $Na^{+}-K^{+}$ ATPase in microsomal fractions of the cortex and medulla of the guinea-pig kidney, isolated rat renal tubule and human erythrocyte ghosts. The present invstigation was undertaken to elucidate the mechanism of GM on human erythrocytes by examining its effect on $Na^{+}-K^{+}$ ATPase activity, actives sodium and potassium transport across red blood cell and $^{3}H-ouabain$ binding to red blood cell membranes. The results obtained are summarized as follows: 1) CM inhibited significantly both the activity of total ATPase and $Na^{+}-K^{+}$ ATPase at all concentrations tested. 2) GM inhibited active $^{22}Na$ efflux across red blood cell. When ouabain is present, the rate of $^{22}Na$ efflux was completely inhibited. When both GM and ouabain were added, the inhibitory effect of active $^{22}Na$ efflux was more pronounced. 3) Active $^{86}Rb$ influx was inhibited significantly by GM. In the presence of ouabain, the rate of $^{86}Rb$ influx is markedly inhibited. But $^{86}Rb$ influx is not appreciably altered by the presence of both GM and ouabain. 4) In the presence of GM, $^{3}H-ouabain$ binding to red blood cell membrane increased. From the above results, it may be concluded that the inhibition of active sodium and potassium transport across red blood cell by gentamicin appears to be due to the inhibition of $Na^{+}-K^{+}$ ATPase activity and an increase in ouabain binding to red blood cell membranes.
It has been well known that the renal cortical blood flow rate was much higher than that of the medulla and the renal blood flow distribution was affected by hemorrhage, volume expansion or salt-loading. The existance of the heterogeneities of glomerular filtration rate and nephron has also been reported. In order to understand the regulations and physiological roles of the heterogeneities, studies on the intrarenal renin-angiotensin system have been focused. Although it is well known that the granularity of iuxtaglomerular cells and renal renin content are more marked in superficial than in the deep glomeruli, their physiological significance is not quite clear. This study was therefore undertaken to clarify changes in renin response and isoelectric ronin profile to TMB-8 in outer, mid and inner cotices of normotensive and hypertensive rats. The basal rate of renin release was highest in outer cortex of Sprague-Dawley rat (SDR), Wistar rat (WR) and spontaneously hypertensive rat (SHR). The basal renin release from outer and inner cortex of SHR was significantly lower than that from those of SDR. The reponse of renin release to TM8-8 was highest in mid cortex and the increase of renin release in response to TMB-8 from inner cortex of SDR was significantly higher than that in SHR. In dehydrated rats, the basal renin release from renal cortical slices of SDR was increased but that from WR and SHR was not. The response of renin release to TMB-8 from mid and inner cortex of dehydrated WR tended to increase. In dehyrated SHR, increase of renin release from inner cortex was significantly higher than that in euhydrated SHR. No significant differences in the isoelectric renin profile were found both in different cortical areas and strains. In dehydrated rats, the percentage of renin form 2 was decreased and those of renin form 5 and 6 were increased. These results suggest that the heterogeneity of renin release from cortical area of euhydrated and dehydrated rats in response to TMB-8 may be related to the changes of renal blood flow and/or calcium metabolism in cortical area. These data also suggest that the renin forms with different isoelectric points may have an physiological significance.
This study was carried out to investigate the branch and distribution of Nervus facialis of the Korean native goat. The observation was made by dissection of embalmed cadavers of ten Korean native goats. The results were as follows; 1. N. facialis arose from the ventrolateral surface of the medulla oblongata. 2. In the facial canal, N. facialis gave off N. petrosus major, N. stapedius and Chorda tympani. 1) N. petrosus major arose from Ganglion geniculi, passed through the pterygoid canal and terminated in Ganglion pterygopalatinum. 2) Chorda tympani joined N. lingualis at the lateral surface of the internal pterygoid muscle. 3. At the exit of the stylomastoid foramen, N. facialis gave off N. caudalis auricularis, Ramus auricularis internus, Ramus stylohyoideus and Ramus digastricus. 1) N. caudalis auricularis arose by two branches in 6 cases and by a single branch in 4 cases. N. caudalis auricularis gave off branches to the caudoauricuIar muscles and the internal surface of the conchal cavity. 2) Ramus auricularis internus arose by a single branch except in 2 cases in which it arose in common with N. caudalis auricularis. It penetrated the caudolateral surface of the tragus and distributed in the skin of the scapha. 3) Ramus stylohyoideus and Ramus digastricus arose separately from N. facialis. 4. In the deep surface of the parotid gland, N. facialis divided into N. auriculopalpebralis, Ramus buccalis dorsalis and Ramus buccalis ventralis. In 6 cases, N. facialis gave off Ramus buccalis ventralis and then divided into N. auriculopalpebralis and Ramus buccalis dorsalis. In 3 cases, N. facialis trifurcated into Ramus buccalis ventralis, Ramus buccalis dorsalis and N. auriculopalpebralis. In one case, N. facialis gave off N. auriculopalpebralis and then divided into Ramus buccalis dorsalis and Ramus buccalis ventralis. 1) Ramus buccalis ventralis ran along the ventral border of the masseter muscle and distributed to the buccinator and depressor labii inferioris muscles. Ramus buccalis ventralis communicated with a branch of Ramus buccalis dorsalis and N. buccalis. In 2 cases, it also communicated with N. mylohyoideus. 2) Ramus buccalis dorsalis communicated with Ramus transverses faciei, N. buccalis, N. infraorbitalis and a branch of Ramus buccalis ventralis. Ramus buccalis dorsalis distributed to the orbicularis oris, caninus, depressor labii inferioris, levator labii superioris, buccinator, malaris, nasolabialis and zygomaticus muscles. 3) N. auriculopalpebralis gave off Rami auriculares rostrales, which supplied the zygomaticoauricularis muscle, the frontoscutularis muscle and the skin of the base of the ear. N. auriculopalpebralis then continued as Ramus zygomaticus, which innervated the frontal muscle, the lateral surface of the base of the horn, the orbicularis oculi muscle and the adjacent skin of the orbit. N. auriculopalpebralis communicated with Nn. auriculares rostrales and Ramus zygomaticotemporalis. In 7 cases, it also communicated with N. infratrochlearis.
The mature guinea pigs were grouped as indicated in the table 1. Radio-active iodine(I-131)in dose of 4.5mci, was administered to the experimental groups. The animals were killed for examination in 1, 7, 14, 28, 42, and 55 days after the administration the radio-active iodine. The thyroid and adrenal glands were observed histologically. The results obtained were as follows; 1. One day after the administration, thyroid epithelial cells were abnormally enlarged. After seven days, specimens taken from the middle of the thyroid showed that the follicles and epithelial cells were changing to fibrous tissue, however, some follicles still remained in the verge of the thyroid. Follicles were not observed after fourteen days. After twenty-eight days, the follicles had all changed to fibrous tissue, and had lost their function. 2. The size of the zonas gromerulosa of adrenal cortex epually, in both male and female, showed slight fluctuation in size with no tendency to be changed. 3. Among the zones of the adrenal glands, zona fasciculata showed marked changes. Zona fasciculata was atrophied in Process of time. In females, it was atrophied significantly(P<0.05) after fourteen days, and highly significant (P<0.01) in twenty-eight and fifty-six days after the administration of radioactive iodine. In males, it also decreased significantly(P<0.05) in seventy-eight days and highly significant(P<0.01) in forty-two and fifty-six days after the administration. 4. The size of the Zona reticularis of adrenal cortex in the females increased significantly (P<0.05) in twenty-eight days after the administration. In males, it showed slight fluctuation until twenty-eight days, but it increased significantly(P<0.05) in forty-two and fifty-six days after the administration. 5. The size of the adrenal medulla increased significantly(P<0.05) in twenty-eight and forty-two days in females. It was increased significantly(P<0.05) in fourth-two days and high significantly(P<0.01) in fifty-six days after the administration.
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