Protective effect of β-glucan on lung injury after cecal ligation and puncture in rats

Objective Understanding the biological mediators involved in the complex inflammatory response of sepsis and acute lung injury offers the possibility of future investigations targeting treatment based on these mediators. This study investigated whether macrophage activator -glucan has a protective effect on acute lung injury in an experimental model of sepsis.Design and setting Experimental study in an experimental research center.Materials 30 rats randomized into three groups (sham, sepsis, and -glucan).Interventions Cecal ligation and puncture were performed in the -glucan and sepsis groups. The -glucan group was given a single intraperitoneal dose of -glucan (4 mg/kg) following cecal ligation.Measurements and results Rats treated with -glucan had fewer circulating neutrophils, more blood monocytes, and higher serum interleukin 6 levels than septic animals. The percentages of neutrophils and lymphocytes from the bronchoalveolar lavage fluid and the myeloperoxidase activity measured in the lung tissue were lower in the -glucan group than in the sepsis group. Less alveolar hemorrhage and neutrophil infiltration were observed in lungs from animals in the -glucan group in the septic groups.Conclusions In this rat model of intra-abdominal sepsis -glucan treatment partially protected against secondary lung injury, decreased lung hemorrhages, and lung neutrophilia. These results suggest that -glucan protects against sepsis-associated lung damage.     

Cardiac damage in acute organophosphate poisoning in rats: Effects of atropine and pralidoxime☆

Anticholinesterase poisoning is an important health problem in our country, and a complete understanding of its underlying mechanisms is essential for the emergency physician. Thus, we aimed to investigate the cardiac biochemical parameters and mortality in dichlorvos-induced poisoning in rats. Rats were randomly divided into 5 groups as control (corn oil), dichlorvos, atropine, pralidoxime, and atropine+pralidoxime groups. Immunohistochemical analyses of apoptosis and inducible nitric oxide synthase showed no change in cardiac tissue for all of the groups. Serum cholinesterase levels were suppressed with dichlorvos, and these reductions were inhibited with atropine and/or pralidoxime pretreatment. Serum levels of creatine kinase, creatine kinase-MB, cardiac troponin I, myoglobin, and N-terminal probrain natriuretic peptide were not affected with poisoning. Malondialdehyde and glutathione levels were not statistically significant between the groups. Although serum nitric oxide levels in the dichlorvos group were lower than those in the control group, cardiac nitric oxide levels in the atropine+pralidoxime group were markedly higher than those in the dichlorvos group. Atropine, pralidoxime, and atropine+pralidoxime pretreatments markedly reduced the mortality. In conclusion, our results implied that measured cardiac markers especially N-terminal probrain natriuretic peptide may not contribute to the early (first 6 hours) diagnosis of cardiotoxicity in dichlorvos-induced poisoning in rats. These results also showed that acute dichlorvos administration did not cause significant cardiac damage, and oxidative stress does not play a marked role in dichlorvos-induced poisoning. Besides, cardiac nitric oxide may produce protective effect on myocardium with atropine+pralidoxime therapy in rats.     

Study on expression of endothelin in experimental cerebral concussion in rats

Objective:To study changes and significance of endothelin (ET) in rat cerebral concussion.Methods 80 Wistar male rats were used for animal model of cerebral concussion,which were sacrificed on 1,3,7,14 and 30 days after injury and the brain tissue were taken off.The expression of ET was studied in the course of cerebral concussion by means of immunohistochemistry.Results:Typical clinical manifestation was observed in the 100g group in which the pathological changes included cerebral vascular constriction and dilatation,congestion and edema of cerebral tissue,neuronal degeneration,necrosis,and obviously decreased even disappeared Nissl bodies.Increased expression of ET was observed on the first day,the positive area was seen in the plasma of endothelial cells in cerebral cortex,hippocampus,cerebellum and thalamus.ET expression peak occurred on the 7th day,the positive area was also found in the plasma of Purkinje cells in the cerebellum.Decreased ET expression was found on 14th day and returned to normal level on the 30th day.Conclusion:The main pathological changes of cerebral concussion contained blood circulation disorder,and degeneration and necrosis of substantial cells.ET was involved n the brain tissue injury during the pathological process of cerebral concussion and might be related to regulation of cerebral vascular reaction,and neuron degeneration and necrosis.     

Effects of neuroprotectant cocktails on focal cerebral ischemia in rats

AIM：To investigate whether cocktail theraphy combined with of neuroprotetants may have more advantages over single agents in treating focal cerebral ischemic cascade,METHODS:With the use of suture occlusin techique,the right middle cerebral artery in rats was occluded.Tirty minutes later,Frutose-1,6-diphosphate(FDP)(50mg/kg,n=20),MK-801(1mg/kg,n=20) and N-acetylcystein (NAC)(150mg/kg,n=20) were singly or combinantly infused intraperitoneally,At the same time the cocktail-treated group(n=20) were infused the above agents combinationly and the control group(n=20) were infused normal saline intraperitoneally.6 hours and 24 hours after focal cerebral ischemia the animals were weighted and neurologically assessed on 5-point scale,The animals were killed,brains were stained 2,3,5-triphenyltetrazolium chloride for assessment of the infarct volume and then embedden onto slides with paraffin for morphological assessment and terminal transferase dUTP nick ending labeling (TUNEL) were carried out for apoptosis and immunohistochemistry were carried out to investigate the changes in bcl-2 .RESULTS:All Neuroprotectants decreased volume of infarction(P&;lt;0.05,P test).While cocktail-treated group showed more distinct decrease than other groups(P&;lt;0.05,F test),FDP-treated group did not decrease the apoptosis of the neurons and did not increase the bcl-2 expression as well MK-801-treated group,NAC-treated group and cocktail-treaed group significantly decreased the apoptosis of the neurons and increased the bcl-2 expression (P&;lt;0.05,F test). With cocktail-treated group showing more distinct effect (P&;lt;0.05,F test).CONCLUSKON:Cocktail may be more effective than single neuroprotectant in this modle.     

Effects of levosimendan and dobutamine in experimental acute endotoxemia: a preliminary controlled study

Objective To test the hypothesis that levosimendan increases systemic and intestinal oxygen delivery (DO₂) and prevents intramucosal acidosis in septic shock. Design Prospective, controlled experimental study. Setting University-based research laboratory. Subjects Nineteen anesthetized, mechanically ventilated sheep. Interventions Endotoxin-treated sheep were randomly assigned to three groups: control (n = 7), dobutamine (10 μg/kg/min, n = 6) and levosimendan (100 μg/kg over 10 min followed by 100 μg/kg/h, n = 6) and treated for 120 min. Measurements and main results After endotoxin administration, systemic and intestinal DO₂ decreased (24.6 ± 5.2 vs 15.3 ± 3.4 ml/kg/min and 105.0 ± 28.1 vs 55.8 ± 25.9 ml/kg/min, respectively; p < 0.05 for both). Arterial lactate and the intramucosal–arterial PCO₂ difference (ΔPCO₂) increased (1.4 ± 0.3 vs 3.1 ± 1.5 mmHg and 9 ± 6 vs 23 ± 6 mmHg mmol/l, respectively; p < 0.05). Systemic DO₂ was preserved in the dobutamine-treated group (22.3 ± 4.7 vs 26.8 ± 7.0 ml/min/kg, p = NS) but intestinal DO₂ decreased (98.9 ± 0.2 vs 68.0 ± 22.9 ml/min/kg, p < 0.05) and ΔPCO₂ increased (12 ± 5 vs 25 ± 11 mmHg, p < 0.05). The administration of levosimendan prevented declines in systemic and intestinal DO₂ (25.1 ± 3.0 vs 24.0 ± 6.3 ml/min/kg and 111.1 ± 18.0 vs 98.2 ± 23.1 ml/min/kg, p = NS for both) or increases in ΔPCO₂ (7 ± 7 vs 10 ± 8, p = NS). Arterial lactate increased in both the dobutamine and levosimendan groups (1.6 ± 0.3 vs 2.5 ± 0.7 and 1.4 ± 0.4 vs. 2.9 ± 1.1 mmol/l, p = NS between groups). Conclusions Compared with dobutamine, levosimendan increased intestinal blood flow and diminished intramucosal acidosis in this experimental model of sepsis. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. This study was solely funded by the Cátedra de Farmacología, Facultad de Ciencias Médicas, Universidad Nacional de La Plata. None of the authors have any financial interests to disclose. This article is discussed in the editorial available at: .     

An experimental study on tissue engineered tendon with human tenocytes

AIM:To investigate the technique of tissue engineered tendon with human tenocytes.METHODS:Human tenocytes in vitro,then the tenocytes were mixed with Polyglycolic Acid (PGA)to form cell-polymer constructs and cul-tured in vitro.After one week,the constructs were surgicallly implanted sub-cutaneously into athymic mice.Specimens were harvested at 6 weeks for gross,histologic examinations and immuno-histological analysis .RESULTS:The engineered tendon resembled natural tendon grossly in both color and tex-ture.Histologically,most tenocytes and collagen bundles were aligned along the longitudinal axis of engineered tendon.CONCLUSION:Human tenocytes be used as seed cell,engineered tendon can be generated in the nude mice by means of tissue engineering technique.     

Effects of tocotrienol on tumor necrosis factor-α/d-galactosamine-induced steatohepatitis in rats

It has been reported that α-tocopherol (α-Toc), a vitamin E analog, is effective for treatment of non-alcoholic steatohepatitis (NASH). However, it is unknown whether or not other vitamin E analogs are effective. Therefore we designed a new rat model of steatohepatitis induced by tumor necrosis factor-α (TNF-α) stimulation, and used it to investigate the effects of vitamin E analogs. The rat liver triglyceride content increased with the dosage of TNF-α/d-galactosamine (GalN), but was suppressed by intake of both tocotrienol (T3) and α-tocopherol. Moreover, lipid peroxides (thiobarbituric acid-reactive substances) level in the liver level was also lower in both groups after tocotrienol and α-Toc intake. Intake of both tocotrienol and α-tocopherol also tended to control the increase of liver damage marker activity. In the tocotrienol and α-tocopherol groups, increases of inflammatory cytokines mRNA expression in the liver were inhibited, and these effects were considered to contribute to improvement of inflammation and fibrosis. The expression of mRNAs for inflammatory cytokines in rat primary hepatocytes was increased by TNF-α stimulation, but was inhibited by addition of α-tocotrienol and γ-tocotrienol. Transforming growth factor-β1 mRNA expression in particular was significantly inhibited by γ-tocotrienol. These findings suggest that tocotrienol species are effective for amelioration of steatohepatitis, and that tocotrienol and α-tocopherol exert a synergistic effect.     

Is n-butyl-2-cyanoacrylate a biocompatible coating material for biodegradable fracture fixation devices? An experimental study on rats

The effect of n-butyl-2-cyanoacrylate monomer and polymer on the repair characteristics of cancellous bone was evaluated in an experimental study in which 105 male Wistar rats were operated on. A transverse drill channel 2mm in diameter and 5mm long in the femoral condyle was filled with a cylindrical implant of n-butyl-2-cyanoacrylate polymer or liquid n-butyl-2-cyanoacrylate monomer, which was polymerized in the tissue. The drill channel was left empty in the control group. Follow-up periods were one, three, six, 12, 24, 36 and 48 weeks. Radiographic, histologic, histomorphometric, oxytetracycline fluorescence and microradiographic studies were done. N-butyl-2-cyanoacrylate polymerdid not delaybone healing and was well tolerated by rat's cancellous bone tissue without signs of foreign body reaction or prolonged inflammation reaction. The polymerization of n-butyl-2-cyanoacrylate monomer caused the development of a narrow zone of bone necrosis or connective tissue around the implant depending on whether or not blood had interfered in the polymerization reaction. Bone necrosis and connective tissue worked as a biological and mechanical obstruction for bone healing towards the implant although there was no disturbance in the regenerative process in the trabecular network surrounding the implant.     

Does β2-adrenergic stimulation attenuate fluid extravasation during hypothermic cardiopulmonary bypass? An experimental study in pigs

Objectives: Hypothermic cardiopulmonary bypass (CPB) is associated with increased fluid filtration, edema formation and, occasionally, organ dysfunction. Cold-induced reduction in endothelial barrier function may play a role. β(2)-adrenergic activation elevates cellular cyclic adenosine monophosphate (cAMP) which maintains endothelial barrier properties. In this study, we tested whether β-adrenergic stimulation could influence the increase in fluid extravasation observed during hypothermic CPB. Materials and methods: Fourteen pigs randomly received terbutaline infusion (T-group) (n=7) or a control infusion (C-group) (n=7). All animals were given 60 min of normothermic CPB, followed by 90 min of hypothermic CPB. Fluid input and losses, plasma volume, colloid osmotic pressures (plasma, interstitial fluid), hematocrit, serum proteins and total tissue water content were measured and the fluid extravasation rates (FER) calculated. Statistics: by SPSS. Values presented as mean ± SD. Repeated measure analysis of variance was performed and a t-test used when appropriate. RESULTS: The commencement of normothermic CPB resulted in a 20% hemodilution, with an abrupt increase in fluid requirements during the first 10 min. FER increased from 0.18 (0.06) pre-bypass to 0.78 (0.27) ml/kg/min (T-group) (p=0.002) and from 0.16 (0.05) to 0.93 (0.26) ml/kg/min (C-group) (p<0.001) with no between-group differences. Thereafter, FER stabilized at a level of 0.32 (0.13) and 0.27 (0.14) ml/kg/min in the T-group and C-group, respectively. After the start of cooling, FER increased in the T-group to 0.55 (0.12) ml/kg/min (P=0.046) and in the C-group to 0.54 (0.13) ml/kg/min (P=0.006), with no between-group differences (P=0.738). CONCLUSION: In the present experimental study, we were unable to demonstrate any clinically relevant modulating effect of terbutaline on fluid extravasation during hypothermic cardiopulmonary bypass.     

Effects of low-dose naloxone on opioid therapy in pediatric patients: a retrospective case-control study

Objective To develop novel therapies that prevent opioid tolerance in critically ill children we examined the effects of low-dose naloxone infusions on patients' needs for analgesia or sedation. Design and setting Matched case-control study in a pediatric intensive care unit at a university children's hospital. Patients We compared 14 pediatric ICU patients receiving low-dose naloxone and opioid infusions with 12 matched controls receiving opioid infusions. Measurements and main results Opioid analgesia and sedative requirements were assessed as morphine- and midazolam-equivalent doses, respectively. No differences were observed between groups in opioid doses at baseline or during naloxone, but in the postnaloxone period opioid doses tended to be lower in the naloxone group. Compared to baseline the naloxone group required more opioids during naloxone but fewer opioids after naloxone. Total sedative doses were comparable at baseline in both groups, with no differences in the postnaloxone period. The naloxone group required less sedation after naloxone but sedation doses were unchanged in controls. The two groups did not differ in pain scores, sedation scores, or opioid side effects. Conclusions Naloxone did not reduce the need for opioid during the infusion period but tended to reduce opioid requirements in the postnaloxone period without additional need for sedation. Randomized clinical trials may examine the effects of low-dose naloxone on opioid tolerance and side effects in pediatric ICU patients requiring prolonged opioid analgesia. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. The authors gratefully acknowledge grant support from National Institute for Child Health and Human Development (NIH grants U10-HD50009 and R01-HD36484 to K.J.S.A.) and ZonMw 940-31-086, 940-39-004 (to D.T.) and the help of J.M. Tilford, Ph.D. for PRISM analyses.     

Effects of metformin and rosiglitazone on peripheral insulin resistance and β-cell function in obesity: a double-blind, randomized, controlled study

Metformin and rosiglitazone combination therapy is known to improve insulin resistance and postpone diabetes mellitus development in subjects with impaired glucose tolerance. This double-blind, randomized, controlled study assessed this combination therapy for preventing type 2 diabetes in obese subjects with hyperinsulinaemia. Subjects received metformin (500 mg three times daily, orally) plus either rosiglitazone (4 mg once daily, orally; n = 94) or placebo (n = 95) and were followed for 6 months. Blood pressure, body fat, body mass index (BMI), lipid and insulin levels were recorded pre- and post-treatment. Metformin plus rosiglitazone significantly decreased blood pressure, lipids, BMI, and fasting and postmeal insulin levels. Metformin plus placebo led to a significant decrease in blood pressure, BMI and lipid levels, but fasting and postmeal insulin levels were unchanged. Adverse events were similar between the two groups. The metformin and rosiglitazone combination increased insulin sensitivity and β-cell function recovered. This approach may represent a therapeutic option for preventing development of type 2 diabetes in obese subjects with hyperinsulinaemia.     

Effects of melatonin on microglia activation in rats with acute intracerebral hemorrhag北大核心CSCD

Objective: To investigate the effects of melatonin on activation of microglia and the changes of superoxide dismutase (SOD) and malondialdehyde (MDA) after intracerebral hemorrhage (ICH) in rats. Methods: One hundred and thirty male SD rats were randomly divided into four groups: normal group, sham-operated group, intracerebral hemorrhage model group (Model group) and melatonin intervention group (MT group). Each group was further divided into 5 subgroups respectively at 12 h, 1 d, 2 d, 4 d and 7 d after modeling. The ICH models were made in SD rats by using Rosenberg methods. Melatonin in dose of 10 mg/kg in solution of 1 mg/mL was given intraperitoneally to rats of MT group. The morphology of microglia was observed under electron microscope. OX42-positive cells were detected by immunohistochemical (ABC) methods. The contents of MDA or the activity of SOD was measured respectively by thiobarbituric acid or xanthine oxidation method. Results: Electron microscope showed that the activation of microglia cell displayed in ameboid shape and swelling of neuron in hemisphere cortex in model group at 2 d after ICH, the activation of microglia cell of the cortex was insignificant in MT group. OX42-positive microglia cell in large amount surrounded the hematoma at 12 h after ICH, peaked at 1 d and lasted for 7 d. OX42-positive microglia cells in MT group were significantly fewer than that in model group at different intervals after ICH (P < 0. 05). The content of MDA in model group increased significantly after ICH, and higher than that in normal group at 7 d, [(0. 875 + 0. 098) nmol/mg prot vs. (0. 725 ± 0. 061) nmol/mg prot, P<0. 05, whereas the activity of SOD changes in the opposite direction, (70.46 ±3. 12) U/mg prot vs. (85. 86 ±4. 95)/U/mg prot, P <0. 05. Compared with model group, the content of MDA were lower and the activity of SOD were higher in MT group after ICH (P < 0. 05). Conclusion: Melatonin provides a protective effect on the damage of nerve cell after ICH. The mechanism might be associated with melatonin by reducing the level of oxidative stress in brain tissue and attenuating the activation of microglia after ICH.     

Effects of mild hypothermia on autophagy in hippocampal CAI neurons in rats after CPR北大核心CSCD

Objective To establish the cardiac arrest-cardiopulmonary resuscitation model in rats, and to observe the effect of mild hypothermia on autophagy in hippocampal CAI neurons after ROSC. Methods A total of 36 Wistar rats were randomly divided into two groups: normal temperature treatment group (NT group) and mild hypothermia treatment group ( HT group). To establish the cardiac arrest- cardiopulmonary resuscitation ( CA-CPR) model in rats by epicardial electrical stimulation induced ventricular fibrillation, and to sacrifice 3 animals in each group to obtain the brain cortex in 2nd and 4th hours after ROSC in order to observe the expression of p-AMPK by electron microscope and LC3 granules through Western blot. The neurological deficit score (NDS) was assessed in 24, 48, 72 hours respectively after ROSC. To sacrifice the animals so as to take the cerebrum in 72 hours after ROSC, then calculate the apoptotic index of the hippocampal CAI neurons, which were dyed through TUNEL method. Results The expression of p-AMPK, Beclin-1 and LC3-E/LC3- I ratio in Normothermia group were all lower than the Mild hypothermia group (P < 0. 05 ) , the neurons plasma of hippocampal CAI area in the Hypothermia group demonstrated obvious LC3 granules formation, the NDS score of the Normothermia group and the Mild hypothermia group in ROSC24h, ROSC48h, ROSC72h were 320vs205, 285vsl40, 266vsl20, respectively. The apoptotic index of the hippocampal CA1 area in the Normothemia group in ROSC72h was higher than the Mild hypothermia group, ( P < 0. 05 ). Conclusions Mild hypothermia after cardiopulmonary resuscitation promotes autophagy of the hippocampal CA1 area neurons in rats and reduce neuronal apoptosis.     

Effects of peripherally restricted κ opioid receptor agonists on pain-related stimulation and depression of behavior in rats

κ opioid receptor agonists that do not readily cross the blood-brain barrier are peripherally restricted and distribute poorly to the central nervous system after systemic administration. Peripherally restricted κ agonists have promise as candidate analgesics, because they may produce antinociception mediated by peripheral κ receptors more potently than they produce undesirable sedative and psychotomimetic effects mediated by central κ receptors. The present study used assays of pain-related stimulation and depression of behavior in rats to compare effects of 1) two peripherally restricted κ agonists [the tetrapeptide D-Phe-D-Phe-D-Ile-D-Arg-NH(2) (ffir) and the nonpeptidic compound ((R,S)-N-[2-(N-methyl-3,4-dichlorophenylacetamido)-2-(3-carboxyphenyl)-ethyl]pyrrolidine hydrochloride (ICI204448)], 2) a centrally penetrating κ agonist (salvinorin A), and 3) several reference drugs, including a nonsteroidal anti-inflammatory drug (NSAID; ketoprofen). Intraperitoneal injection of dilute lactic acid served as a noxious stimulus to stimulate a stretching response and depress intracranial self-stimulation (ICSS) maintained by the delivery of electrical brain stimulation to the medial forebrain bundle. Acid-stimulated stretching was blocked by ketoprofen, the peripherally restricted κ agonists, and salvinorin A. However, acid-induced depression of ICSS was blocked only by ketoprofen. The peripherally restricted κ agonists had little effect, and salvinorin A exacerbated acid-induced depression of ICSS. These results suggest that peripherally restricted κ agonists may be safer than centrally penetrating κ agonists but less efficacious than NSAIDS or μ opioid receptor agonists to block pain-related depression of behavior; however, the peripheral selectivity of ffir and ICI204448 is limited, and future studies with κ agonists capable of greater peripheral selectivity are warranted.     

Does dehydration affect thickness of the pyloric muscle? An experimental study

Congenital hypertrophic pyloric stenosis (CHPS) is a common condition in infancy associated with smooth muscle hypertrophy and resulting in pyloric outlet obstruction. The final diagnosis of CHPS is based on precise ultrasonographic measurements of length and width of the pyloric muscle. Based on our clinical and sonographic experience, we observed that smaller measurements of the pyloric muscle were obtained in dehydrated infants than in children examined after proper fluid restoration. The clinical importance of these observations was evident because false-negative results could be obtained. An experimental animal work followed, proving our clinical observation to be true. A significant difference of about 30% to 50% was found between measurements of the muscle thickness of the gastric and pyloric muscles in a state of water deprivation, as compared with a state of full hydration (p < 0.05). Based on our preliminary results, we suggest that children with suspected CHPS should be well hydrated before the ultrasound (US) examination is performed, to avoid false-negative results and a consequent delay in treatment.     

Effects of Leptin Replacement Therapy on Pancreatic β-Cell Function in Patients With Lipodystrophy

OBJECTIVE

Leptin administration is known to directly modulate pancreatic β-cell function in leptin-deficient rodent models. However, human studies examining the effects of leptin administration on β-cell function are lacking. In this study, we examined the effects (16–20 weeks) of leptin replacement on β-cell function in patients with lipodystrophy.

RESEARCH DESIGN AND METHODS

In a prospective, open-label, currently ongoing study, we studied the effects of leptin replacement on β-cell function in 13 patients with congenital or acquired lipodystrophy. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution from plasma glucose and C-peptide levels measured during oral glucose tolerance tests (OGTTs) performed at baseline and after 16–20 weeks of leptin replacement. β-Cell glucose sensitivity and rate sensitivity were assessed by mathematical modeling of OGTT.

RESULTS

There was a significant decrease in triglycerides, free fatty acids, and glycosylated hemoglobin levels (A1C) after leptin therapy. Patients with lipodystrophy have high fasting and glucose-stimulated ISR. However, leptin therapy had no significant effect on fasting ISR, total insulin secretion during OGTT, β-cell glucose sensitivity, rate sensitivity, or insulin clearance.

CONCLUSIONS

In contrast to the suppressive effects of leptin on β-cell function in rodents, 16–20-week treatment with leptin in lipodystrophy patients did not significantly affect insulin secretion or β-cell function in leptin-deficient individuals with lipodystrophy.     

Preventive effect of β-analyl-l-histidinato zinc on bone metabolism in rats fed on low-calcium and vitamin D-deficient diets

The effect of β-alanyl-l-histidinato zinc (AHZ) on bone metabolism in the femoral diaphysis of rats fed on low-calcium and vitamin D-deficient diets was investigated. Rats were orally administered AHZ (10, 30, and 100 mg/kg per day) for 14 days and were killed on the 15th day. Feeding with low-calcium and vitamin D-deficient diets caused a significant decrease in serum 25-hydroxy-vitamin D₃, calcium, and inorganic phosphorus concentrations. These decreases were not prevented by AHZ administration. Meanwhile, the femoral-diaphyseal calcium and phosphorus contents were significantly reduced by feeding with the dificient diets. Decrease in bone calcium content was significantly prevented by the doses of 30 and 100 mg AHZ/kg. Furthermore, the dose of 100 mg AHZ/kg produced a significant increase in bone deoxyribonucleic acid (DNA) content and alkaline phosphatase activity in rats fed on the deficient diets. Bone zinc content in the deficient rats was significantly increased by the doses of AHZ (30 and 100 mg/kg). The present results suggest that oral administration of AHZ has a preventive effect in the development of deteriorating bone metabolism in rats fed on low-calcium and vitamin D-deficient diets.