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Selection experiment for increased egg production under 23 H and 24 H light-dark cycles in the domestic fowl.

A selection experiment was conducted for increased rate of lay under 23-h (23 HS line) and 24-h (24 HS line) light-dark cycles over 5 generations. In generation 5, rate of lay was higher in the 23 HS line than in the 24 HS line, and the proportion of hens with mean intra-sequence intervals of less than 24 h in the 23 HS line increased to 88% in the generation 5 from 15% in the base generation. The realised heritability for rate of lay was 0.25 plus/minus 0.04 in the 23 HS line and 0.15 plus/minus 0.05 in the 24 HS line. Egg weight and shell weight decreased in both lines, and the decrease in the proportion of shell was larger in the 23 HS line than in the 24 line. It is suggested that a regimen of 23 h light and dark may be an effective environment for selection to improve the laying performance of a population approaching a plateau for egg production.

Animals↗

L-selectin blockade and liver function in rats after uncontrolled hemorrhagic shock.

Hemorrhagic shock (HS) and resuscitation can be seen as a global body ischemia-reperfusion (I/R) injury characterized by neutrophil infiltration and organ damage. Liver dysfunction occurs early after HS. Adhesion molecules are needed for the first steps ofneutrophil migration. Thus, the purpose of this study was to investigate the role of L-selectin in the liver after uncontrolled HS and resuscitation. Forty-eight Sprague Dawley rats were subjected to uncontrolled HS and resuscitation. Animals were divided into three groups: sham, uncontrolled HS and resuscitation, and uncontrolled HS and resuscitation with anti-L-selectin treatment. At 6 we evaluated liver injury tests, liver tissue myeloperoxidase (MPO), and liver histology. Survival was followed for 3 days and compared between groups. Statistical analysis included Fisher's exact test and one-way analysis of variance. Survival significantly increased from 30% in the control group to 60% in the treated group (p < .05). Hepatocellular and structural injury as well as neutrophil infiltration was significantly decreased in treated animals (p < .05). Thus, blockade of L-selectin resulted in decreased hepatocellular injury and increased survival in our model of uncontrolled HS. Selectins may be important therapeutic targets for blockade in the treatment of HS.

Animals↗

Temporal effect of hemoglobin resuscitation on sepsis survival.

Hemoglobin (Hb)-based oxygen carriers are promising resuscitation fluids for hemorrhagic shock. However, infusion of large amounts of Hb-based material could interfere with reticuloendothelial function potentiating postresuscitation sepsis mortality. We investigated the temporal relationship between hemorrhage-resuscitation and sepsis survival. Male SD rats were subjected to hemorrhage and resuscitated with shed blood volumes of purified human hemoglobin solution (HS). Sepsis was induced by cecal ligation and puncture (CLP) 24 h before, 0, 24, or 72 h after hemorrhage/resuscitation (H/R) and survival was monitored. In additional animals with or without Hb resuscitation, hepatic heme oxygenase-1 (HO-1) gene expression and HO activity were assessed. Seven-day survival for animals resuscitated with HS prior to sepsis induction was significantly higher than other groups. Animals resuscitated with HS showed hepatic HO-1 gene expression while non-HS resuscitated animals did not. In addition, hepatic HO activity levels were significantly higher in HS resuscitated animals than non-HS resuscitated animals. In conclusion, HS resuscitation does not appear to enhance postresuscitation sepsis mortality. Rather, when conducted concomitantly or prior to sepsis, HS resuscitation appears to improve survival from a subsequent sepsis challenge.

Animals↗

The role of gender in salt-induced hypertension.

To evaluate gender differences in salt-induced hypertension, female and male Dahl salt-sensitive rats were fed high (8.0% NaCl, HS) and low (0.3% NaCl, LS) salt diets. During a 3-week treatment period, blood pressure was significantly elevated in both female and male HS groups compared to their respective LS groups. The blood pressure and 4 week mortality rate of the female HS group, however, were significantly lower than those of the male HS group. Renal and aortic blood flows were reduced in male rats on HS diet compared to the LS group, while, in females, renal blood flow was elevated and aortic flow was maintained while on HS diet. Plasma prostaglandin E2 and prostacyclin levels were higher in females than males and unaffected by diet. In contrast, plasma nitric oxide levels were reduced by HS, regardless of gender. In isolated aortic rings, HS diet caused a smaller elevation in the stimulated norepinephrine release ratio in female rats than in males. Thus, salt-induced hypertension is associated with a reduction in levels of nitric oxide regardless of gender. Plasma prostaglandin E2 and prostacyclin levels were higher in females. Taken together, the higher plasma prostaglandin levels and reduced sympathetic activity in females may be contributing factors in their lower blood pressure and reduced mortality.

Animals↗

Intestinal dopaminergic activity in obese and lean Zucker rats: response to high salt intake.

The present study examined intestinal dopaminergic activity and its response to high salt (HS, 1% NaCl over a period of 24 hours) intake in obese (OZR) and lean Zucker rats (LZR). The basal Na+,K+-ATPase activity (nmol Pi/mg protein/min) in the jejunum of OZR was higher than in LZR on normal salt (NS) (OZR-NS = 111.3 +/- 6.0 vs. LZR-NS = 88.0 +/- 8.3). With the increase in salt intake, the basal Na+,K+-ATPase activity significantly increased in both animals (OZR-HS = 145.9 +/- 11.8; LZR-HS = 108.8 +/- 6.7). SKF 38393 (10 nM), a specific D1-like dopamine receptor agonist, inhibited the jejunal Na+,K+-ATPase activity in OZR on HS intake, but failed to inhibit enzyme activity in OZR on NS intake and LZR on NS and HS intakes. The aromatic L-amino acid decarboxylase (AADC) activity in OZR was lower than in LZR on NS intake. The HS intake increased AADC activity in OZR, but not in LZR. During the NS intake the jejunal monoamine oxidase (MAO) activity in OZR was similar to that in LZR. The HS intake significantly decreased MAO activity in both OZR and LZR. The jejunal COMT activity in OZR was higher than in LZR on NS intake. The HS intake reduced COMT activity in OZR but not LZR. It is concluded that inhibition of jejunal Na+,K+-ATPase activity through D1 dopamine receptors is dependent on salt intake in OZR, whereas in LZR, the enzyme failed to respond to the activation of D1 dopamine receptors irrespective of their salt intake.

Animals↗

QSulf1 remodels the 6-O sulfation states of cell surface heparan sulfate proteoglycans to promote Wnt signaling.

The 6-O sulfation states of cell surface heparan sulfate proteoglycans (HSPGs) are dynamically regulated to control the growth and specification of embryonic progenitor lineages. However, mechanisms for regulation of HSPG sulfation have been unknown. Here, we report on the biochemical and Wnt signaling activities of QSulf1, a novel cell surface sulfatase. Biochemical studies establish that QSulf1 is a heparan sulfate (HS) 6-O endosulfatase with preference, in particular, toward trisulfated IdoA2S-GlcNS6S disaccharide units within HS chains. In cells, QSulf1 can function cell autonomously to remodel the sulfation of cell surface HS and promote Wnt signaling when localized either on the cell surface or in the Golgi apparatus. QSulf1 6-O desulfation reduces XWnt binding to heparin and HS chains of Glypican1, whereas heparin binds with high affinity to XWnt8 and inhibits Wnt signaling. CHO cells mutant for HS biosynthesis are defective in Wnt-dependent Frizzled receptor activation, establishing that HS is required for Frizzled receptor function. Together, these findings suggest a two-state "catch or present" model for QSulf1 regulation of Wnt signaling in which QSulf1 removes 6-O sulfates from HS chains to promote the formation of low affinity HS-Wnt complexes that can functionally interact with Frizzled receptors to initiate Wnt signal transduction.

Animals↗

Chédiak-Higashi gene in humans I. Impairment of natural-killer function.

Natural-killer (NK)-cell function was profoundly depressed in donors homozygous for the Chediak-Steinbrinck-Higashi syndrome (C-HS) gene when compared with age- and sex-matched normals. This apparent defect was not simply a result of a delayed response because little cytolysis was evident in kinetics experiments even after 24 h of incubation. NK cells from C-HS donors failed to lyse adherent (MDA, CEM, and Alab) or nonadherent (K562 and Molt-4) tumor cell lines or nontransformed human fetal fibroblasts. Therefore, the apparent C-HS defect was not a result of a shift in target selectivities. In addition, the depressed reactivity did not appear to be a result of suppressor cells or factors because: (a) enriched NK populations (nonadherent lymphocytes bearing receptors for the Fc portion of IgG) from C-HS donors were low in NK-cell function, (b) C-HS mononuclear cells did not inhibit the cytotoxicity of normal cells in coculture experiments, and (c) cells from the C-HS donors remained poorly reactive even after culture for up to 7 d. The nature of the defective NK activity in C-HS patients is not clear but may lie within the lytic mechanism rather than at the level of the recognition structure or population size because the frequency of target-binding cells was normal. In vitro NK activity could be partially restored by interferon treatment. Combined with the results presented in the following paper (4), these observations suggest that the C-HS gene causes a selective immunodeficiency disorder, mainly involving NK cells. This finding, in conjunction with the high incidence of spontaneous possibly malignant, lymphoproliferative disorders in these patients, may have important implications regarding the theory of immune surveillance mediated by NK cells.

Adult↗

Etiological point mutations in the hereditary multiple exostoses gene EXT1: a functional analysis of heparan sulfate polymerase activity.

Hereditary multiple exostoses (HME), a dominantly inherited genetic disorder characterized by multiple cartilaginous tumors, is caused by mutations in members of the EXT gene family, EXT1 or EXT2. The corresponding gene products, exostosin-1 (EXT1) and exostosin-2 (EXT2), are type II transmembrane glycoproteins which form a Golgi-localized heterooligomeric complex that catalyzes the polymerization of heparan sulfate (HS). Although the majority of the etiological mutations in EXT are splice-site, frameshift, or nonsense mutations that result in premature termination, 12 missense mutations have also been identified. Furthermore, two of the reported etiological missense mutations (G339D and R340C) have been previously shown to abrogate HS biosynthesis (McCormick et al. 1998). Here, a functional assay that detects HS expression on the cell surface of an EXT1-deficient cell line was used to test the remaining missense mutant exostosin proteins for their ability to rescue HS biosynthesis in vivo. Our results show that EXT1 mutants bearing six of these missense mutations (D164H, R280G/S, and R340S/H/L) are also defective in HS expression, but surprisingly, four (Q27K, N316S, A486V, and P496L) are phenotypically indistinguishable from wild-type EXT1. Three of these four "active" mutations affect amino acids that are not conserved among vertebrates and invertebrates, whereas all of the HS-biosynthesis null mutations affect only conserved amino acids. Further, substitution or deletion of each of these four residues does not abrogate HS biosynthesis. Taken together, these results indicate that several of the reported etiological mutant EXT forms retain the ability to synthesize and express HS on the cell surface. The corresponding missense mutations may therefore represent rare genetic polymorphisms in the EXT1 gene or may interfere with as yet undefined functions of EXT1 that are involved in HME pathogenesis.

Amino Acid Sequence↗

Analysis of the interaction between adeno-associated virus and heparan sulfate using atomic force microscopy.

Adeno-associated virus (AAV) has been widely used as a viral vector to deliver genes to animal and human tissues in gene therapy studies. Both AAV-2 and AAV-3 use cell surface heparan sulfate (HS), a highly sulfated polysaccharide, as a receptor to establish infections. In this study, we used atomic force microscopy (AFM) to investigate the interaction of HS and AAV. A silicon chip functionalized with HS was used as a substrate for binding AAV for AFM analysis. To validate our approach, we found that the binding of AAV-2 to the HS surface was effectively competed by soluble HS, suggesting that the binding of AAV-2 to the functionalized surface was specific. In addition, we examined the binding of various AAV serotypes, including AAV-1, AAV-2, AAV-3, and AAV-5, to the HS surface. As expected, only AAV-2 and AAV-3 bound, whereas AAV-1 and AAV-5 did not. This observation was consistent with the previous conclusion that AAV-1 and AAV-5 do not use HS as a receptor for infection. In conclusion, we developed a novel approach to investigate the interaction of AAV virus with its polysaccharide-based receptor at the level of a single viral particle. Given that HSs serve as receptor for numerous viruses, this approach has the potential to become a generalized method for studying interactions between the viral particle and HS, as well as other virus-cell interactions, and potentially serve as a platform for screening antiviral therapies.

Cell Line↗

Cloacal gland and testes development in male Japanese quail selected for divergent adrenocortical responsiveness.

The time course of sexual development in male quail from lines selected for either a reduced (low stress, LS) or an exaggerated (high stress, HS) plasma corticosterone response to brief restraint was determined. Sexual development was assessed by examination of cloacal gland area (CAREA) and volume (CVOL), proportion of individuals that produced cloacal gland foam, and the intensity of cloacal gland foam production (CFP) at 4, 5, 6, 8, 10, 14, and 16 wk of age. These intervals encompass ages during which growing, photostimulated quail would be expected to evolve from being totally prepubescent to well into adulthood. Testes weight (TW) and the proportion of individuals that had achieved a combined TW of 500 mg (PI500) were also measured at 6 and 16 wk of age. Mean CAREA and CVOL were similar in LS and HS quail at 4 wk of age. Beginning at 5 wk of age and thereafter, CAREA was greater (P < 0.05) in LS than in HS quail. Similarly, beginning at 6 wk of age and thereafter, CVOL was greater (P < 0.05) in LS than in HS quail. More LS than HS birds also expressed foam at 4 (P < 0.05), 5 (P = 0.15), and 6 wk (P < 0.05) of age. From 8 wk on, all birds were in foam production. CFP results mimicked those found for CAREA and CVOL in that LS quail tended toward higher CFP values than HS quail at all intervals of measurement. TW were higher (P < 0.02) in LS than HS quail when data from the 2 ages at which testes were harvested were combined. At 6 wk of age, the LS and HS birds showed a PI500 line difference (P < 0.08) of 1.0 and 0.91, respectively; by 16 wk, all birds exhibited a maximum PI500. The results suggest that 1) selection for reduced adrenocortical responsiveness in Coturnix is accompanied by an accelerated onset of puberty in males, and 2) enhanced reproductive development in LS males remains extant throughout early to middle-age adulthood.

Adrenal Cortex↗

Pattern of snoring in obstructive sleep apnea patients and in heavy snorers.

We measured respiratory mechanical characteristics during sleep in five heavy, nonapneic snorers (HS) and in five obstructive sleep apnea (OSA) patients. In two HS and in two OSA patients we obtained lateral pharyngeal cineradiographic images during sleep while snoring. Flow limitation preceded all snores in both HS and OSA. Pattern of snoring, hysteresis and temporal relationship between supraglottic pressure (Psg) and flow rate were different in HS and OSA. Maximal flow during snoring was less (p less than 0.05) in OSA (0.18 +/- 0.07 liter/second) than in HS (0.36 +/- 0.06 liter/second). Linear supraglottic resistance during inspiratory snoring was higher, though not significantly, in OSA patients (7.11 +/- 3.01 cm H2O/liter/second) than in HS (4.80 +/- 2.83 cm H2O/liter/second). We conclude that: 1) Snoring is characterized by high frequency oscillations of the soft palate, pharyngeal walls, epiglottis and tongue. 2) Flow limitation appears to be a sine qua non for snoring during sleep. 3) The pattern of snoring is different in OSA and HS. 4) Pharyngeal size during snoring is probably larger in HS than in OSA patients.

Adult↗

Differentiation of hidroacanthoma simplex from clonal seborrheic keratosis--an immunohistochemical study.

Hidroacanthoma simplex (HS) is an uncommon poroid neoplasm confined within the epidermis. The clinical features of HS are not distinctive and histopathologically HS may be confused with clonal seborrheic keratosis (CSK) if cystic or ductal structure is not present. The purpose of our study was to differentiate HS from CSK by the immunohistochemical expressions of various cytokeratins, CEA, CD1a, and S-100 protein, as well as by the degrees of deposition of melanins and glycogen. Four cases of HS and seven cases of CSK were included in the research. In contrast with CSK, HS showed a very low density of Langerhans cells (19.9 +/- 7.7 versus 3.1 +/- 1.0 CD1a (+) cells/mm, P = 0.027) and sparse melanin deposition in the nests. However, HS could not be set apart from CSK by the expressions of cytokeratins. The nests of both HS and CSK showed very similar patterns of cytokeratin expression and seemed to be mainly composed of basaloid cells with focal differentiation toward epidermal suprabasal cells.

Acrospiroma↗

14-methoxymetopon, a potent opioid, induces no respiratory depression, less sedation, and less bradycardia than sufentanil in the dog.

UNLABELLED: Opioids of the mu-receptor type depress respiration and induce addiction. At 10-min intervals 14-methoxymetopon (HS-198), which is 20,000 times more potent than morphine in the acethylcholine-writhing test, was given in graded IV doses (3, 6, and 12 microg/kg) to awake, trained canines (n = 7). The following variables were derived: PaO(2), PaCO(2), heart rate (lead II of the electrocardiogram), mean arterial blood pressure, relative changes in the delta domain and the beta domain of the electroencephalogram, the somatosensory evoked potential, and the skin-twitch reflex to electrical stimuli. Thereafter, 20 microg/kg naltrexone was given for reversal. After a washout period, the same animals were exposed to similar doses of sufentanil (SUF) followed by naltrexone. Both opioids induced a dose-related bradycardia and hypotension. The maximal bradycardic effect was 19% after HS-198 and 42% after SUF (P < 0.005). The maximal hypotension was 6% after HS-198 and 20% after SUF (P < 0.01). In the electroencephalogram, power in the delta band increased by 288% after HS-198 and by 439% after SUF (P < 0.01); simultaneously, power in the beta band decreased by 71% and by 95.7%, respectively (P < 0.01). PaO(2) decreased by 41% after SUF and by 4% after HS-198, and PaCO(2) increased by 56.8% and 6.6% in SUF and HS-198, respectively (P < 0.001). Both opioids induced a dose-related depression in the somatosensory evoked potential and increased tolerance to skin-twitch. The maximal effect was 92.7% after SUF and 81.3% after HS-198 was not significant. Naltrexone reversed all changes back to control. Compared with SUF, HS-198 does not induce hypoxia and hypercarbia, induces less hypotension and bradycardia, and induces less sedative effects. IMPLICATIONS: Compared with sufentanil, 14-methoxymetopone does not induce hypoxia and hypercarbia, induces less hypotension and bradycardia, and induces less sedative effects (electroencephalogram). Antinociception is similar to sufentanil (skin-twitch method, amplitude depression in the evoked potential). All effects are reversed by naltrexone. Interaction of kappa-receptor is suggested.

Anesthetics, Intravenous↗

Intraoperative colloid administration reduces postoperative nausea and vomiting and improves postoperative outcomes compared with crystalloid administration.

The debate over colloid versus crystalloid as the best solution for intraoperative fluid resuscitation is not resolved. Published studies have shown that mortality is not related to the specific fluid used for resuscitation. In addition, the quality of postoperative recovery between colloid and crystalloid has not been well investigated. In a prospective, blinded fashion, we investigated the effects of colloid and crystalloid resuscitation on nausea and vomiting and on the postoperative patient recovery profile. Patients undergoing major elective noncardiac surgery were randomized to receive 6% hetastarch in saline (HS-NS), 6% hetastarch in balanced salt (HS-BS), or lactated Ringer's solution (LR) on the basis of a fluid administration algorithm. The anesthetic was standardized. Hemodynamic targets included maintenance of arterial blood pressure, heart rate, and urine output within a predefined range. A postoperative morbidity survey was performed at baseline and daily after surgery. Ninety patients participated in the study, with 30 patients in each group. The amounts of study fluid (mean +/- SD) administered were 1301 +/- 1079 mL, 1448 +/- 759 mL, and 5946 +/- 1909 mL for the HS-NS, HS-BS, and LR groups, respectively (P < 0.05, HS-NS and HS-BS versus LR). Both the HS-NS and HS-BS (colloid) groups had a significantly less frequent incidence of nausea and vomiting, use of rescue antiemetics, severe pain, periorbital edema, and double vision. We concluded that intraoperative fluid resuscitation with colloid, when compared with crystalloid administration, is associated with an improvement in the quality of postoperative recovery.

Antiemetics↗

Interictal EEG, hippocampal atrophy, and cell densities in hippocampal sclerosis and hippocampal sclerosis associated with microscopic cortical dysplasia.

The EEG characteristics of isolated hippocampal sclerosis (HS) and HS associated with other types of temporal lobe pathology are not well defined. The pathologic substrate may be an important variable in determining seizure-free outcome. The objective of this study was to define the distribution of epileptiform discharges in patients with HS and HS associated with microscopic dysplasia, and to examine their relationship with hippocampal atrophy and cell loss. Thirty-four patients (15 women and 19 men; mean age, 30.6 +/- 11.2 years), all with good outcomes after temporal lobectomy (Engel classes I and II), were included. The characteristics studied were frequency and distribution of spikes, MRI-based hippocampal volume ratios, and quantitative hippocampal cell density in various subregions. The isolated HS group showed a trend to a higher percentage of epileptiform discharges maximal at the anterior temporal electrodes (89.87 +/- 17.0%; 79.5 +/- 28.2% in the dual-pathology group). The isolated HS group had, on average, significantly more cell loss (P < 0.001). There was a significant negative correlation between the amount of cell loss in the CA1 area and both anterior temporal spikes and hippocampal ratios (P < 0.05). Isolated HS and dual pathology show minimal differences in interictal spike distribution and frequency. More widespread spike distributions in severe isolated HS compared with patients with less cell loss is probably the result of less organized limbic circuitry.

Adult↗

Increased hippocampal AMPA and NMDA receptor subunit immunoreactivity in temporal lobe epilepsy patients.

This study determined if hippocampal AMPA and NMDA subunit immunoreactivity (IR) in temporal lobe epilepsy patients was increased compared with nonseizure autopsies. Hippocampi from hippocampal sclerosis patients (HS; n = 26) and nonsclerosis cases (non-HS: n = 12) were compared with autopsies (n = 6) and studied for GluR1, GluR2/3, NMDAR1, and NMDAR2 IR gray values (GV) along with fascia dentata and Ammon's horn neuron densities. Compared with autopsies, non-HS cases with similar neuron densities and HS patients with decreased neuron densities showed: (a) Increased GluR1 GVs in the fascia dentata molecular layer: (b) increased NMDAR1 GVs in the CA3-1 stratum radiatum and greater IR within pyramids; and (c) increased GluR2/3 and NMDAR2 GVs throughout all hippocampal subfields. Furthermore, HS patients showed that relative to the outer molecular layer: (a) GluR1 GV differences were decreased in the CA4/hilar region and CA1 stratum radiatum compared with autopsies; and (b) NMDAR2 GV differences were increased in the inner molecular layer compared with non-HS cases. In temporal lobe seizure patients, these results indicate that AMPA and NMDA receptor subunit IR was increased in HS and non-HS hippocampi compared with nonseizure autopsies. In humans, these findings support the hypothesis that glutamate receptor subunits are increased in association with chronic temporal lobe seizures, which may enhance excitatory neurotransmission and seizure susceptibility.

Adult↗

Effects of ACE inhibition on left ventricular failure and oxidative stress in Dahl salt-sensitive rats.

Dahl salt-sensitive (DS) rats fed high-salt diet exert compensated left ventricular (LV) hypertrophy and eventually develop heart failure. Oxidative stress has been shown to be involved in myocardial remodeling and failure and thus might play an important role in this transition from hypertrophy to failure. We measured the amount of reactive oxygen species (ROS) in the myocardium from DS rats by using electron spin resonance spectroscopy with 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl (hydroxy-TEMPO) and also examined the effects of chronic angiotensin-converting enzyme (ACE) inhibition on the transition. We divided DS rats (5 weeks old, 150-200 g) into three groups: low-salt (0.3% NaCl) diet for 10 weeks (LS group), high-salt (8% NaCl) diet for 10 weeks (HS-10+V group), and high-salt diet and cilazapril (10 mg/kg body weight per day) started after 5 weeks of high-salt diet and maintained for 5 weeks (HS-10+Cil group). Systolic blood pressure (mm Hg) was significantly elevated in the HS-10+V (229+/-5) and HS-10+Cil (209+/-5) groups compared with the LS group (141+/-2). The amount of myocardial ROS was not changed after 5 weeks of high-salt diet, but significantly increased in HS-10+V rats compared with LS rats, and was abolished in the HS-10+Cil group. HS-10+V rats exerted the clinical signs of heart failure, including increased lung weight and pleural effusion, associated with LV hypertrophy and LV cavity dilatation. In the HS-10+Cil group, signs of heart failure were significantly attenuated despite only a modest reduction in systolic blood pressure (-20 mm Hg). The progression of LV failure after hypertrophy in high-salt-loaded DS hypertensive rats was associated with increased myocardial ROS, and ACE inhibitor could prevent this transition from compensated hypertrophy to failure.

Angiotensin-Converting Enzyme Inhibitors↗

Coadministration of methylprednisolone with hypertonic saline solution improves overall neurological function and survival rates in a chronic model of spinal cord injury.

OBJECTIVE: We previously demonstrated that administration of 7.5% hypertonic saline (HS) significantly improved spinal cord blood flow and neurological outcomes after spinal cord injury. The aim of this study was to determine whether hypertonicity would enhance the effects of methylprednisolone (MP), further improving neurological function. METHODS: Rat spinal cords were compressed for 10 minutes with 50 g of weight, and neurological function was assessed for 28 days, using the Basso-Beattie-Bresnahan locomotor rating scale. The control group received an intravenous injection of isotonic saline (IS) (5 ml/kg). Group 1 received an intravenous injection of 7.5% HS (5 ml/kg). Group 2 received an intravenous injection of MP (30 mg/kg) and IS (5 ml/kg). Group 3 received an intravenous injection of MP (30 mg/kg) administered with 7.5% HS (5 ml/kg). RESULTS: At 24 hours after spinal cord injury, the combination of MP plus HS provided significant (P < 0.01) neurological improvements, compared with all other treatment groups. At 10 days after injury, the animals that had received MP plus HS exhibited significantly (P < 0.01) higher Basso-Beattie-Bresnahan scores, compared with the MP plus IS and control groups. The median survival time was significantly (P < 0.01) increased for the MP plus HS group (28 d), compared with the MP plus IS group (16 d). Because of the dramatic decrease in survival rates at 28 days after injury, there was a significant (P < 0.01) difference in neurological function only between the MP plus HS group and the control group. CONCLUSION: The results indicate that the administration of HS may enhance the delivery of MP and prevent immunosuppression, leading to improvements in overall neurological function and survival rates after spinal cord injury.

Animals↗